Suppression of N-Glycosylation of Zinc Finger Protein 471 Affects Proliferation, Invasion, and Docetaxel Sensitivity of Tongue Squamous Cell Carcinoma via Regulation of c-Myc.

Zinc finger protein 471 (ZNF471) is a member of the Krüppel-related domain zinc finger protein family, and has recently attracted attention because of its anti-cancer effects. N-glycosylation regulates expression and functions of the protein. This study aimed to investigate the effects of ZNF471 N-glycosylation on the proliferation, invasion, and docetaxel sensitivity of tongue squamous cell carcinoma (TSCC). It analyzed the expression, function, and prognostic significance of ZNF471 in TSCC using bioinformatics techniques such as gene differential expression analysis, univariate Cox regression analysis, functional enrichment analysis, and gene set enrichment analysis. Using site-specific mutagenesis, this study generated three mutant sites for ZNF471 N-glycosylation to determine the effect of N-glycosylation on ZNF471 protein levels and function. Quantitative real-time PCR, Western blot analysis, and immunohistochemistry tests confirmed the down-regulation of ZNF471 expression in TSCC. Low expression of ZNF471 is associated with poor prognosis of patients with TSCC. Overexpression of ZNF471 in vitro retarded the proliferation of TSCC cells and suppressed cell invasion and migration ability. Asparagine 358 was identified as a N-glycosylation site of ZNF471. Suppressing N-glycosylation of ZNF471 enhanced the protein stability and promoted the translocation of protein to the cell nucleus. ZNF471 binding to c-Myc gene promoter suppressed oncogene c-Myc expression, thereby playing the anti-cancer effect and enhancing TSCC sensitivity to docetaxel. In all, N-glycosylation of ZNF471 affects the proliferation, invasion, and docetaxel sensitivity of TSCC via regulation of c-Myc.

Predicting Survival Using Whole-Liver MRI Radiomics in Patients with Hepatocellular Carcinoma After TACE Refractoriness.

PURPOSE: To develop a model based on whole-liver radiomics features of pre-treatment enhanced MRI for predicting the prognosis of hepatocellular carcinoma (HCC) patients undergoing continued transarterial chemoembolization (TACE) after TACE-resistance. MATERIALS AND METHODS: Data from 111 TACE-resistant HCC patients between January 2014 and March 2018 were retrospectively collected. At a ratio of 7:3, patients were randomly assigned to developing and validation cohorts. The whole-liver were manually segmented, and the radiomics signature was extracted. The tumor and liver radiomics score (TLrad-score) was calculated. Models were trained by machine learning algorithms and their predictive efficacies were compared. RESULTS: Tumor stage, tumor burden, body mass index, alpha-fetoprotein, and vascular invasion were revealed as independent risk factors for survival. The model trained by Random Forest algorithms based on tumor burden, whole-liver radiomics signature, and clinical features had the highest predictive efficacy, with c-index values of 0.85 and 0.80 and areas under the ROC curve of 0.96 and 0.83 in the developing cohort and validation cohort, respectively. In the high-rad-score group (TLrad-score > - 0.34), the median overall survival (mOS) was significantly shorter than in the low-rad-score group (17 m vs. 37 m, p < 0.001). A shorter mOS was observed in patients with high tumor burden compared to those with low tumor burden (14 m vs. 29 m, p = 0.007). CONCLUSION: The combined radiomics model from whole-liver signatures may effectively predict survival for HCC patients continuing TACE after TACE refractoriness. The TLrad-score and tumor burden are potential prognostic markers for TACE therapy following TACE-resistance.

Heterogeneous bimetallic selenides encapsulated within graphene aerogel as advanced anodes for sodium ion batteries.

Metal selenides are promising anode candidates for sodium ion batteries (SIBs) because of their high theoretical capacity, low cost, and environmental friendship. However, the low rate capability at high current density due to its inherent low electrical conductivity and poor cycle stability caused by inevitable volume variations during cycling frustrate its practical applications. Herein, we have developed a simple metallic-organic frameworks (MOFs)-derived selenide strategy to synthesize a series of heterogeneous bimetallic selenides encapsulated within graphene aerogels (GA) as anodes for SIBs. The bimetallic selenides/GA composites have unique structural characteristics that can shorten the migration path for Na+/electrons and accommodate the volume variations via additional void space during cycling. The built-in electric fields induced at the heterointerfaces can greatly reduce the activation energy for rapid charge transfer kinetics and promote the diffusion of Na+/electrons. GA is also beneficial for accommodating the volume variations during cycling and improving conductivity. As an advanced anode for SIBs, the MoSe2-Cu1.82Se@GA with a special porous octahedron can deliver the highest capacity of 444.8 mAh/g at a high rate of 1 A/g even after 1000 cycles among the bimetallic selenides/GA composites.

Exploration of quantitative-effectiveness association between acupuncture temporal parameters and stable chronic obstructive pulmonary disease: A systematic review and dose-response meta-analysis of randomized controlled trials.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is a globally common chronic respiratory disease with a high morbidity and mortality rate. Acupuncture has been proven effective for COPD. A dose-response meta-analysis was conducted to assess the correlation between the acupuncture temporal parameters(session, frequency, and duration) and its effectiveness in patients with stable COPD. METHODS: Acupuncture randomized controlled trials on COPD were searched in eight databases from their inception to June 2023. The "doses" were defined as the acupuncture session, frequency, and duration. The outcomes mainly included Forced Expiratory Volume in one-second rate (FEV1%) and Six-minute Walking Distance (6MWD). The assessment of bias risk and literature quality were conducted independently using the Cochrane risk of bias tool and the Standards for reporting interventions in clinical trials of acupuncture. The dose-response relationship was modeled using robust error element regression, and meta-analysis was operated by R 4.3.1 and Stata 15.0. The protocol was registered in PROSPERO with the registration number CRD42023401406. RESULT: Out of 1669 records, 17 RCTs with 1165 participants were finally included in the meta-analysis. There was notable heterogeneity among the studies, but sensitivity analysis demonstrated good robustness. The findings revealed a significant improvement in the following outcomes for stable COPD patients in the acupuncture group: FEV1% (MD=3.50, 95%CI: 2.05-4.95), 6MWD (MD=47.39, 95%CI: 29.29-65.50), St. George's respiratory questionnaire (SGRQ; MD=-8.25, 95%CI: -11.38 to -5.12); COPD assessment test (CAT; MD=-2.91, 95%CI: -3.99 to -1.83). The relationship between the acupuncture session, duration, and FEV1%, 6MWD followed a "Λ" curve pattern, while the relationship between acupuncture frequency and FEV1%, 6MWD exhibited logarithmic growth. Firstly, After 12 acupuncture sessions, FEV1% and 6MWD increased by 7.06% (95%CI: 4.56-9.55) and 36.28 m (95%CI: 20.37-52.20), respectively. The peak improvement in FEV1% and 6MWD was observed after 18 acupuncture sessions (MD=7.89, 95% CI: 5.33-10.45) and 45 sessions (MD=125.43, 95% CI: 72.80-178.07) each. Additionally, weekly acupuncture resulted in a 4.14% improvement in FEV1% (95% CI: 2.55-5.72) and a 42.49 m increase in 6MWD (95%CI: 17.16-67.81). Notably, the maximum effects on FEV1% and 6MWD improvement were achieved with different acupuncture frequencies, specifically three times a week (MD=6.00, 95% CI: 5.34-6.66) and once a day(MD=112.41, 95% CI: 77.27-147.56), respectively. Furthermore, after a 28-day duration of acupuncture treatment, FEV1% increased by 4.74% (95% CI: 3.73-5.75) and 6MWD increased by 47.34 m (95%CI: 22.01-72.67). During 60 days of acupuncture treatment, the FEV1% and 6MWD improvement reached their highest levels at 8.76% (95% CI: 7.05-10.47) and 88.06 m (95% CI: 45.96-130.16), respectively. CONCLUSION: Acupuncture was effective in improving FEV1%, 6MWD, SGRQ, and CAT in patients with stable COPD. There was a dose-response relationship between the time parameters of acupuncture (session, frequency, and duration) and the efficacy of COPD treatment (FEV1% and 6MWD). The minimal clinically important difference could be achieved after 12 acupuncture sessions. Acupuncture with a medium-frequency (2-3 times per week) over 60 days may result in the greatest improvement in FEV1%, while higher-frequency acupuncture (5-7 times per week) for 2 months may lead to the maximum improvements in 6MWD. It indicated that the optimal acupuncture duration for different indicators remains consistent, while the optimal frequencies may differ. To confirm these results, it is necessary to conduct multicenter, large-scale randomized controlled trials. ETHICS AND DISSEMINATION: Ethical approval is not required for literature-based studies. The results will be published in peer-reviewed journals or conferences.

Biological scaffold as potential platforms for stem cells: Current development and applications in wound healing.

Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

Facial adult female acne in China: An analysis based on artificial intelligence over one million.

BACKGROUND: To further clarify the acne profile of Chinese adult women, we included 1,156,703 adult women. An artificial intelligence algorithm was used to analyze images taken by high-resolution mobile phones to further explore acne levels in Chinese adult women. METHOD: In this study, we assessed the severity of acne by evaluating patients' selfies through a smartphone application. Furthermore, we gathered basic user information through a questionnaire, including details such as age, gender, skin sensitivity, and dietary habits. RESULTS: This study showed a gradual decrease in acne severity from the age of 25 years. A trough was reached between the ages of 40 and 44, followed by a gradual increase in acne severity. In terms of skin problems and acne severity, we have found that oily skin, hypersensitive skin, frequent makeup application and unhealthy dietary habits can affect the severity of acne. For environment and acne severity, we observed that developed city levels, cold seasons and high altitude and strong radiation affect acne severity in adult women. For the results of the AI analyses, the severity of blackheads, pores, dark circles and skin roughness were positively associated with acne severity in adult women. CONCLUSIONS: AI analysis of high-res phone images in Chinese adult women reveals acne severity trends. Severity decreases after 25, hits a low at 40-44, then gradually rises. Skin type, sensitivity, makeup, diet, urbanization, seasons, altitude, and radiation impact acne. Blackheads, pores, dark circles, and skin roughness are linked to acne severity. These findings inform personalized skincare and public health strategies for adult women.

High-throughput discovery of highly selective reversible hMAO-B inhibitors based on at-line nanofractionation.

Human monoamine oxidase B (hMAO-B) has emerged as a pivotal therapeutic target for Parkinson's disease. Due to adverse effects and shortage of commercial drugs, there is a need for novel, highly selective, and reversible hMAO-B inhibitors with good blood-brain barrier permeability. In this study, a high-throughput at-line nanofractionation screening platform was established with extracts from Chuanxiong Rhizoma, which resulted in the discovery of 75 active compounds, including phenolic acids, volatile oils, and phthalides, two of which were highly selective novel natural phthalide hMAO-B inhibitors that were potent, selective, reversible and had good blood‒brain permeability. Molecular docking and molecular dynamics simulations elucidated the inhibition mechanism. Sedanolide (IC50 = 103 nmol/L; SI = 645) and neocnidilide (IC50 = 131 nmol/L; SI = 207) demonstrated their excellent potential as hMAO-B inhibitors. They offset the limitations of deactivating enzymes associated with irreversible hMAO-B inhibitors such as rasagiline. In SH-SY5Y cell assays, sedanolide (EC50 = 0.962 µmol/L) and neocnidilide (EC50 = 1.161 µmol/L) exhibited significant neuroprotective effects, comparable to the positive drugs rasagiline (EC50 = 0.896 µmol/L) and safinamide (EC50 = 1.079 µmol/L). These findings underscore the potential of sedanolide as a novel natural hMAO-B inhibitor that warrants further development as a promising drug candidate.

Host proteins interact with viral elements and affect the life cycle of highly pathogenic avian influenza A virus H7N9.

Host-virus interactions can significantly impact the viral life cycle and pathogenesis; however, our understanding of the specific host factors involved in highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection is currently restricted. Herein, we designed and synthesized 65 small interfering RNAs targeting host genes potentially associated with various aspects of RNA virus life cycles. Afterward, HPAI H7N9 viruses were isolated and RNA interference was used to screen for host factors likely to be involved in the life cycle of HPAI H7N9. Moreover, the research entailed assessing the associations between host proteins and HPAI H7N9 proteins. Twelve key host proteins were identified: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), adaptor related protein complex 3 subunit sigma 1 (AP3S1), ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COP)A, COPG1, heat shock protein family A (Hsp70) member 1A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18. Co-immunoprecipitation revealed intricate interactions between viral proteins (hemagglutinin, matrix 1 protein, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and these host proteins, presumably playing a crucial role in modulating the life cycle of HPAI H7N9. Notably, ANXA5, AP2S1, AP3S1, ATP5A1, HSP90A1, and RAB18, were identified as novel interactors with HPAI H7N9 proteins rather than other influenza A viruses (IAVs). These findings underscore the significance of host-viral protein interactions in shaping the dynamics of HPAI H7N9 infection, while highlighting subtle variations compared with other IAVs. Deeper understanding of these interactions holds promise to advance disease treatment and prevention strategies.

Research progress of circadian rhythm in cardiovascular disease: A bibliometric study from 2002 to 2022.

Background: Given that the circadian rhythm is intricately linked to cardiovascular physiological functions, the objective of this investigation was to employ bibliometric visualization analysis in order to scrutinize the trends, hotspots, and prospects of the circadian rhythm and cardiovascular disease (CVD) over the past two decades. Methods: A thorough exploration of the literature related to the circadian rhythm and CVD was conducted via the Web of Science Core Collection database spanning the years 2002-2022. Advanced software tools, including citespace and VOSviewer, were employed to carry out a comprehensive analysis of the co-occurrence and collaborative relationships among countries, institutions, journals, references, and keywords found in this literature. Furthermore, correlation mapping was executed to provide a visual representation of the data. Results: The present study encompassed a total of 3399 published works, comprising of 2691 articles and 708 reviews. The publications under scrutiny were primarily derived from countries such as the United States, Japan, and China. The most prominent research institutions were found to be the University of Vigo, University of Minnesota, and Harvard University. Notably, the journal Chronobiology International, alongside its co-cited publications, had the most substantial contribution to the research in this field. Following an exhaustive analysis, the most frequently observed keywords were identified as circadian rhythm, blood pressure, hypertension, heart rate, heart rate variability, and melatonin. Furthermore, a nascent analysis indicated that future research might gravitate towards topics such as inflammation, metabolism, oxidative stress, and autophagy, thereby indicating new directions for investigation. Conclusion: This analysis represents the first instance of bibliometric scrutiny pertaining to circadian rhythm and its correlation with cardiovascular disease (CVD) through the use of visualization software. Notably, this study has succeeded in highlighting the recent research frontiers and prominent trajectories in this field, thereby providing a valuable contribution to the literature.

Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.

PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

Synthesis and characterization of core-shell high-nickel cobalt-free layered LiNi0.95Mg0.02Al0.03O2@Li2ZrO3 cathode for high-performance lithium ion batteries.

High-nickel cobalt-free layered cathode is regarded as a highly potential cathode material for the next generation lithium ion batteries (LIBs) because of its high energy density, low cost and environmentally benign. However, the poor cycle performance caused by its intrinsic unstable structure and chemo-mechanical instability frustrates its practical applications. Herein, we have developed a new core-shell high-nickel cobalt-free layered LiNi0.95Mg0.02Al0.03O2@Li2ZrO3 (LZO-NMA9523) cathode for high-performance LIBs. The Li2ZrO3 coating layer firstly helps to suppress and reduce the degree of Li+/Ni2+ cation mixing during the material preparation process. In addition, the Li2ZrO3 coating layer can not only accommodate the volume variations and enhance the electricity of the active materials, but also effectively inhibit the harmful irreversible phase transition during the charging/discharging process, thus greatly stabilizing the structure of the high-nickel cobalt-free cathode. As an advanced cathode for LIBs, the LZO-NMA9523 exhibits an excellent reversible capacity of 146.9 mAh g-1 after 100 cycles at 0.5 C with capacity retention of about 80%. This study provides a possible high-nickel cobalt-free layered cathode material for the next generation LIBs.

Dependence of evolution of Cyanobacteria superiority on temperature and nutrient use efficiency in a meso-eutrophic plateau lake.

Algal blooms in lakes have been a challenging environmental issue globally under the dual influence of human activity and climate change. Considerable progress has been made in the study of phytoplankton dynamics in lakes; The long-term in situ evolution of dominant bloom-forming cyanobacteria in meso-eutrophic plateau lakes, however, lacks systematic research. Here, the monthly parameters from 12 sampling sites during the period of 1997-2022 were utilized to investigate the underlying mechanisms driving the superiority of bloom-forming cyanobacteria in Erhai, a representative meso-eutrophic plateau lake. The findings indicate that global warming will intensify the risk of cynaobacteria blooms, prolong Microcystis blooms in autumn to winter or even into the following year, and increase the superiority of filamentous Planktothrix and Cylindrospermum in summer and autumn. High RUETN (1.52 Biomass/TN, 0.95-3.04 times higher than other species) under N limitation (TN < 0.5 mg/L, TN/TP < 22.6) in the meso-eutrophic Lake Erhai facilitates the superiority of Dolichospermum. High RUETP (43.8 Biomass/TP, 2.1-10.2 times higher than others) in TP of 0.03-0.05 mg/L promotes the superiority of Planktothrix and Cylindrospermum. We provided a novel insight into the formation of Planktothrix and Cylindrospermum superiority in meso-eutrophic plateau lake with low TP (0.005-0.07 mg/L), which is mainly influenced by warming, high RUETP and their vertical migration characteristics. Therefore, we posit that although the obvious improvement of lake water quality is not directly proportional to the control efficacy of cyanobacterial blooms, the evolutionary shift in cyanobacteria population structure from Microcystis, which thrives under high nitrogen and phosphorus conditions, to filamentous cyanobacteria adapted to low nitrogen and phosphorus levels may serve as a significant indicator of water quality amelioration. Therefore, we suggest that the risk of filamentous cyanobacteria blooms in the meso-eutrophic plateau lake should be given attention, particularly in light of improving water quality and global warming, to ensure drinking water safety.

[Mechanism of astragaloside â £ combined with Panax notoginseng saponins in regulating angiogenesis to treat cerebral ischemia based on network pharmacology and experimental verification].

Network pharmacology and animal and cell experiments were employed to explore the mechanism of astragaloside Ⅳ(AST Ⅳ) combined with Panax notoginseng saponins(PNS) in regulating angiogenesis to treat cerebral ischemia. The method of network pharmacology was used to predict the possible mechanisms of AST Ⅳ and PNS in treating cerebral ischemia by mediating angiogenesis. In vivo experiment: SD rats were randomized into sham, model, and AST Ⅳ(10 mg·kg~(-1)) + PNS(25 mg·kg~(-1)) groups, and the model of cerebral ischemia was established with middle cerebral artery occlusion(MCAO) method. AST Ⅳ and PNS were administered by gavage twice a day. the Longa method was employed to measure the neurological deficits. The brain tissue was stained with hematoxylin-eosin(HE) to reveal the pathological damage. Immunohistochemical assay was employed to measure the expression of von Willebrand factor(vWF), and immunofluorescence assay to measure the expression of vascular endothelial growth factor A(VEGFA). Western blot was employed to determine the protein levels of vascular endothelial growth factor receptor 2(VEGFR2), VEGFA, phosphorylated phosphatidylinositol 3-kinase(p-PI3K), and phosphorylated protein kinase B(p-AKT) in the brain tissue. In vitro experiment: the primary generation of rat brain microvascular endothelial cells(rBEMCs) was cultured and identified. The third-generation rBMECs were assigned into control, model, AST Ⅳ(50 µmol·L~(-1)) + PNS(30 µmol·L~(-1)), LY294002(PI3K/AKT signaling pathway inhibitor), 740Y-P(PI3K/AKT signaling pathway agonist), AST Ⅳ + PNS + LY294002, and AST Ⅳ + PNS + 740Y-P groups. Oxygen glucose deprivation/re-oxygenation(OGD/R) was employed to establish the cell model of cerebral ischemia-reperfusion injury. The cell counting kit-8(CCK-8) and scratch assay were employed to examine the survival and migration of rBEMCs, respectively. Matrigel was used to evaluate the tube formation from rBEMCs. The Transwell assay was employed to examine endothelial cell permeability. Western blot was employed to determine the expression of VEGFR2, VEGFA, p-PI3K, and p-AKT in rBEMCs. The results of network pharmacology analysis showed that AST Ⅳ and PNS regulated 21 targets including VEGFA and AKT1 of angiogenesis in cerebral infarction. Most of these 21 targets were involved in the PI3K/AKT signaling pathway. The in vivo experiments showed that compared with the model group, AST Ⅳ + PNS reduced the neurological deficit score(P<0.05) and the cell damage rate in the brain tissue(P<0.05), promoted the expression of vWF and VEGFA(P<0.01) and angiogenesis, and up-regulated the expression of proteins in the PI3K/AKT pathway(P<0.05, P<0.01). The in vitro experiments showed that compared with the model group, the AST Ⅳ + PNS, 740Y-P, AST Ⅳ + PNS + LY294002, and AST Ⅳ + PNS + 740Y-P improved the survival of rBEMCs after OGD/R, enhanced the migration of rBEMCs, increased the tubes formed by rBEMCs, up-regulated the expression of proteins in the PI3K/AKT pathway, and reduced endothelial cell permeability(P<0.05, P<0.01). Compared with the LY294002 group, the AST Ⅳ + PNS + LY294002 group showed increased survival rate, migration rate, and number of tubes, up-regulated expression of proteins in the PI3K/AKT pathway, and decreased endothelial cell permeability(P<0.05,P<0.01). Compared with the AST Ⅳ + PNS and 740Y-P groups, the AST Ⅳ + PNS + 740Y-P group presented increased survival rate, migration rate, and number of tubes and up-regulated expression of proteins in the PI3K/AKT pathway, and reduced endothelial cell permeability(P<0.01). This study indicates that AST Ⅳ and PNS can promote angiogenesis after cerebral ischemia by activating the PI3K/AKT signaling pathway.

Geogenic Phosphorus Enrichment in Groundwater due to Anaerobic Methane Oxidation-Coupled Fe(III) Oxide Reduction.

Accumulation of geogenic phosphorus (P) in groundwater is an emerging environmental concern, which is closely linked to coupled processes involving FeOOH and organic matter under methanogenic conditions. However, it remains unclear how P enrichment is associated with methane cycling, particularly the anaerobic methane oxidation (AMO). This study conducted a comprehensive investigation of carbon isotopes in dissolved inorganic carbon (DIC), CO2, and CH4, alongside Fe isotopes, microbial communities, and functions in quaternary aquifers of the central Yangtze River plain. The study found that P concentrations tended to increase with Fe(II) concentrations, δ56Fe, and δ13C-DIC, suggesting P accumulation due to the reductive dissolution of FeOOH under methanogenic conditions. The positive correlations of pmoA gene abundance versus δ13C-CH4 and Fe concentrations versus δ13C-CH4, and the prevalent presence of Candidatus_Methanoperedens, jointly demonstrated the potential significance of Fe(III)-mediated AMO process (Fe-AMO) alongside traditional methanogenesis. The increase of P concentration with δ13C-CH4 value, pmoA gene abundance, and Fe concentration suggested that the Fe-AMO process facilitated P enrichment in groundwater. Redundancy analysis confirmed this assertion, identifying P concentration as the primary determinant and the cooperative influence of Fe-AMO microorganisms such as Candidatus_Methanoperedens and Geobacter on P enrichment. Our work provided new insights into P dynamics in subsurface environments.

The effect of indoor air filtration on biomarkers of inflammation and oxidative stress: a review and meta-analysis of randomized controlled trials.

Improvement of indoor air quality is beneficial for human health. However, previous studies have not reached consistent conclusions regarding the effects of indoor air filtration on inflammation and oxidative stress. This study aims to determine the relationship between indoor air filtration and inflammation and oxidative stress biomarkers. We conducted an electronic search that evaluated the association of indoor air filtration with biomarkers of inflammation and oxidative stress in five databases (PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus) from the beginning to April 23, 2023. Outcomes included the following markers: interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), malondialdehyde (MDA), 8-hydroxy-2deoxyguanosine (8-OHdG), and 8-iso-prostaglandinF2α (8-isoPGF2α). We extracted data from the included studies according to the system evaluation and the preferred reporting item for meta-analysis (PRISMA) guidelines and used the Cochrane risk of bias tool to assess bias risk. Our meta-analysis included 15 studies with 678 participants to assess the combined effect size. The meta-analysis demonstrated that indoor air filtration could have a marked reduction in IL-6 (SMD: -0.275, 95% CI: -0.545 to -0.005, p = 0.046) but had no significant effect on other markers of inflammation or oxidative stress. Subgroup analysis results demonstrated a significant reduction in 8-OHdG levels in the subgroup with < 1 day of duration (SMD: -0.916, 95% CI: -1.513 to -0.320; p = 0.003) and using filtrete air filter (SMD: -5.530, 95% CI: -5.962 to -5.099; p < 0.001). Our meta-analysis results depicted that indoor air filtration can significantly reduce levels of inflammation and oxidative stress markers. Considering the adverse effects of air pollution on human health, our study provides powerful evidence for applying indoor air filtration to heavy atmospheric pollution.

Safety and efficacy of anlotinib combined with taxane and lobaplatin in neoadjuvant treatment of clinical stage II/III triple-negative breast cancer in China (the neoALTAL trial): a single-arm, phase 2 trial.

Background: Anlotinib is a new type of tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors 1/2/3, platelet-derived growth factor receptors α/ß, and fibroblast growth factor receptors 1-4 and c-Kit, with a broad spectrum of inhibitory effects on tumor angiogenesis and growth. It has been proven effective in HER2-negative metastatic breast cancer, but its efficacy in early-stage triple-negative breast cancer (TNBC) is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients with TNBC. Methods: Patients with clinical stage II/III TNBC were treated with 5 cycles of anlotinib (12 mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 ,d1, q3w or nab-paclitaxel 125 mg/m2, d1 and d8, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The primary endpoint was pathological complete response (pCR; ypT0/is ypN0) and the secondary endpoints include breast pCR (bpCR), axillary pCR (apCR), residual cancer burden (RCB), objective response rate (ORR), survival, and safety. Exploratory endpoints were efficacy biomarkers based on Fudan University Shanghai Cancer Center Immunohistochemical (FUSCC IHC) classification for TNBC and next-generation sequencing (NGS) of DNA from tumor tissue and blood samples of patients with 425-gene panel. This trial is registered with www.chictr.org.cn (ChiCTR2100043027). Findings: From Jan 2021 to Aug 2022, 48 patients were assessed and 45 were enrolled. All patients received at least one dose of study treatment and underwent surgery. The median age was 48.5 years (SD: 8.7), 71% were nodal involved, and 20% had stage III. In the intention-to-treat population, 26 out of 45 patients achieved pCR (57.8%; 90% CI, 44.5%-70.3%), and 39 achieved residual cancer burden class 0-I (86.7%; 95% CI, 73.2%-94.9%). The bpCR and apCR rate were 64.4% (29/45) and 71.9% (23/32), respectively. No recurrence or metastasis occurred during the short-term follow-up. Based on the FUSCC IHC-based subtypes, the pCR rates were 68.8% (11/16) for immunomodulatory subtype, 58.3% (7/12) for basal-like immune-suppressed subtype and 33.3% (4/12) for luminal androgen receptor subtype, respectively. NGS revealed that the pCR were 77% (10/13) and 50% (14/28) in MYC-amplified and wild-type patients, respectively, and 78% (7/9) and 53% (17/32) in gBRCA1/2-mutated and wild-type patients, respectively. The median follow-up time of the study was 14.9 months (95% CI: 13.5-16.3 months). There was no disease progression or death during neoadjuvant therapy. No deaths occurred during postoperative follow-up. In the safety population (N = 45), Grade 3 or 4 treatment emergent adverse events occurred in 29 patients (64%), and the most common events were neutropenia (38%), leukopenia (27%), thrombocytopenia (25%), anemia (13%), and hypertension (13%), respectively. Interpretation: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and encouraging antitumor activity for patients with clinical stage II/III TNBC. Funding: Chongqing Talents Project, Chongqing Key Project of Technology Innovation and Application Development and Chongqing Outstanding Youth Natural Science Foundation.

Hand skeletal features of children and adolescents with different growth statuses and periods.

Background: The hand skeletal features of children and adolescents at different growth statuses and development periods, and the correlation between these skeletal features and hand asymmetric force are currently unclear. Thus, this study sought to investigate the hand skeletal features of children and adolescents at different growth statuses and at different periods of development, and the correlation between these skeletal features and asymmetric force in hands. Methods: A retrospective study was performed on subjects aged 4-20 years with good growth status (group A) or short stature (group B). Additional subjects aged 4-20, 21-40, and >40 years were enrolled in groups C, D, and E, respectively. All the subjects underwent left-hand posteroanterior X-ray radiography. Brachymesophalangia-V (BMP-V), conical epiphysis, epiphysis/metaphysis symmetry of the proximal phalanx (ESP), and the angle of the metacarpal-phalangeal axis were analyzed. Results: Of the 654 children and teenagers aged 4-20 years (median: 11 years) enrolled in the study, 432 were allocated to group A, of whom 237 (54.9%) were male and 195 (45.1%) were female, and 222 matched cases were allocated to group B, of whom 112 (50.5%) were male and 110 (49.5%) were female. The first to third ESPs were significantly (P<0.05) greater in group A than in group B, while the first to third angles of the metacarpal-phalangeal axis were significantly (P<0.05) smaller in group A than in group B. The correlation analysis revealed a highly significant (P<0.01) negative correlation between the ESP and angle of the metacarpal-phalangeal axis (r=-0.948, -0.926, -0.940, -0.885, and -0.848, respectively). The incidence of BMP-V was 15.4% in all patients, while that of conical epiphysis was 19.5%. The incidence of BMP-V and conical epiphysis was significantly (P<0.05) smaller in group A than in group B (11.1% vs. 23.8% for BMP-V and 16.6% vs. 25.2% for conical epiphysis, respectively). Additionally, 216 subjects were enrolled in group C (108 male and 108 female), 185 subjects were enrolled in in group D (93 male and 92 female), and 176 subjects were enrolled in in group E (104 male and 72 female). The second to fifth ESPs in group C were significantly (P<0.05) smaller than those in both groups D and E, while the second to fifth angles of the metacarpal-phalangeal axis were significantly (P<0.05) larger in group C than in both groups D and E. A BMP-V was present in 35 (16.2%) patients in group C, 8 (4.3%) in group D, and 2 (1.1%) in group E, and the difference among the three groups was statistically significant (P<0.05). Conclusions: The epiphyseal symmetry of the proximal phalanges is poor in short stature children and adolescents, and the angle between the metacarpal and phalangeal axes is larger in children and adolescents with short stature than those with normal height and good growth status. A negative correlation was found between the epiphyseal symmetry of the proximal phalanges and asymmetrical stress.

Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose-effect relationship of acupuncture. METHODS/DESIGN: This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. DISCUSSION: This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Unveiling the antioxidant superiority of α-tocopherol: Implications for vitamin E nomenclature and classification.

Since the discovery of tocopherols a century ago, α-tocopherol has been distinguished for its unique biological functions. In this study, we aim to elucidate the unique characteristics of α-tocopherol from a chemical perspective. Utilizing density functional theory (DFT) calculations, we evaluated the thermodynamic and kinetic properties of tocopherols, tocotrienols and their oxidation products. Our findings highlight the superior thermodynamic and kinetic properties of α-tocopherol. Although tocopherol substrates generally exhibit similar reactivities, α-tocopherol is distinguished by a larger gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) in intermediates, indicating a potential for greater energy release and favoring reaction progression. Moreover, α-tocopherol shows enhanced efficiency in quenching radical intermediates, especially when combined with vitamin C. All these dates provide valuable support for the naming of vitamin E.

[A multicenter clinical study on the treatment of lateral epicondylitis of humerus by manipulation].

OBJECTIVE: To investigate clinical effect of tendons pulling,poking and kneading for the treatment of external humeral epicondylitis. METHODS: From January 2018 to December 2021,a multicenter randomized controlled study was performed to collect 192 patients with external humeral epicondylitis in Wangjing Hospital,Beijing Dianli Hospital,and Beijing Fengsheng Osteotraumatology Hospital,respectively,and they were divided into treatment group and control group by random number table method. There were 96 patients in treatment group,including 36 males and 60 females,aged from 28 to 60 years old with an average of (41.20±5.50) years old;the course of disease ranged from 1 to 14 days with an average of (5.24±1.35) days;they were treated once every other day for 2 weeks. There were 96 patients in control group ,including 33 males and 63 females,aged from 26 to 60 years old with an average of (43.35±7.75) years old;the course of disease ranged from 1 to 14 days with an average of (5.86±1.48) days;they were treated with topical voltaalin combined with elbow joint fixation for 2 weeks. Visual analogue scale (VAS) and Hospital for Surgery Scoring System (HSS) elbow pronation and supination angles,wrist metacarpal flexion and dorsal extension angles,elbow tenderness between two groups were compared before treatment and at 1,3,5,7,11 and 13 days after treatment;Hospital for Surgery Scoring System 2 (HSS2) was compared before treatment and the final treatment. RESULTS: All patients were followed up for 10 to 14 days with an average of (12±1.6) days. VAS between treatment group and control group before treatment were 6.83±1.36 and 6.79±1.58,respectively,and decreased to 1.49±1.09 and 2.11±1.81 after the final treatment. VAS of treatment group were significantly lower than those of control group at 1,3,5,7,9,11 and 13 days after treatment (P<0.05). HSS between two groups were 61.73±11.00 and 36.47±12.45 before treatment,respectively,and increased to 94.42±5.9 and 91.44±9.11 at the final treatment. HSS of treatment group were significantly higher than those of control group at 1,3,5,7,9,11 and 13 days after treatment (P<0.05). On the 5th day after treatment,the external and internal rotation angles of elbow in treatment group were (66.41±12.69) ° and (66.35±13.54) °,while those in control group were (62.08±16.03) ° and (61.77±16.35) °. On the 7th day after treatment,the external and internal rotation angles of elbow were (69.79±12.64) ° and (70.02±13.55) ° in treatment group,and (65.28±15.86) ° and (65.09±16.67) ° in control group. Elbow joint motion in treatment group was higher than that in control group (P<0.05). On the 5th day after treatment,angles of wrist dorsiflexion and palm flexion were (39.43±15.94) ° and (46.68±11.10) ° in treatment group,and (38.51±18.49) ° and (44.27±13.58) ° in control group. On the 7th day after treatment,angles of wrist dorsiflexion and palm flexion were (42.52±16.50) ° and (49.23±10.96) ° in treatment group,and (41.18±20.09) ° and (46.64±14.63) ° in control group. The motion of wrist joint in treatment group was higher than that in control group (P<0.05). On the 13th day after treatment,HSS2 in treatment group 93.61±6.32 were higher than those in control group 92.06±7.94(P<0.05). There was no significant difference in elbow tenderness between two groups at each time point (P>0.05). CONCLUSION: Voltaren external treatment combined with elbow fixation and tendons pulling,poking and kneading could effectively improve symptoms of external humeral epicondylitis. Compared with voltaren external treatment,tendons pulling,poking and kneading has advantages of longer analgesic time and better elbow function recovery.