Colossal Ferroelectric Photovoltaic Effect in Inequivalent Double-Perovskite Bi2FeMnO6 Thin Films.

Double perovskite films have been extensively studied for ferroelectric order, ferromagnetic order, and photovoltaic effects. The customized ion combinations and ordered ionic arrangements provide unique opportunities for bandgap engineering. Here, a synergistic strategy to induce chemical strain and charge compensation through inequivalent element substitution is proposed. A-site substitution of the barium ion is used to modify the chemical valence and defect density of the two B-site elements in Bi2FeMnO6 double perovskite epitaxial thin films. We dramatically increased the ferroelectric photovoltaic effect to ∼135.67 µA/cm2 from 30.62 µA/cm2, which is the highest in ferroelectric thin films with a thickness of less than 100 nm under white-light LED irradiation. More importantly, the ferroelectric polarization can effectively improve the photovoltaic efficiency of more than 5 times. High-resolution HAADF-STEM, synchrotron-based X-ray diffraction and absorption spectroscopy, and DFT calculations collectively demonstrate that inequivalent ion plays a dual role of chemical strain (+1.92 and -1.04 GPa) and charge balance, thereby introducing lattice distortion effects. The reduction of the oxygen vacancy density and the competing Jahn-Teller distortion of the oxygen octahedron are the main phenomena of the change in electron-orbital hybridization, which also leads to enhanced ferroelectric polarization values and optical absorption. The inequivalent strategy can be extended to other double perovskite systems and applied to other functional materials, such as photocatalysis for efficient defect control.

The systematic identification of survival-related alternative splicing events and splicing factors in glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, making it one of the most life-threatening human cancers. Nevertheless, research on the mechanism of action between alternative splicing (AS) and splicing factor (SF) or biomarkers in GBM is limited. AS is a crucial post-transcriptional regulatory mechanism. More than 95% of human genes undergo AS events. AS can diversify the expression patterns of genes, thereby increasing the diversity of proteins and playing a significant role in the occurrence and development of tumors. In this study, we downloaded 599 clinical data and 169 transcriptome analysis data from The Cancer Genome Atlas (TCGA) database. Besides, we collected AS data about GBM from TCGA-SpliceSeq. The overall survival (OS) related AS events in GBM were determined through least absolute shrinkage and selection operator (Lasso) and Cox analysis. Subsequently, the association of these 1825 OS-related AS events with patient survival was validated using the Kaplan-Meier survival analysis, receiver operating characteristic curve, risk curve analysis, and independent prognostic analysis. Finally, we depicted the AS-SF regulatory network, illustrating the interactions between splicing factors and various AS events in GBM. Additionally, we identified three splicing factors (RNU4-1, SEC31B, and CLK1) associated with patient survival. In conclusion, based on AS occurrences, we developed a predictive risk model and constructed an interaction network between GBM-related AS events and SFs, aiming to shed light on the underlying mechanisms of GBM pathogenesis and progression.

Unique Organic Crystal Skeleton Based on N-Phenyl-Carbazole Derivatives with Adjustable Room Temperature Phosphorescence and Highly Stable Inclusion Ability to Dichloromethane.

Monosubstituted 9-(2-bromophenyl)-carbazole (1Br1CZ) and disubstituted 9,9'-(2,4-dibromo-1,3-phenylene) bis(9H-carbazole) (2Br2CZ) are synthesized by introducing bromine into ortho-phenyl position of 9-phenyl-carbazole (PhCZ). The decomposition temperature with 5% mass loss and melting point of 2Br2CZ crystal are 360 and 230 °C. The highest occupied molecular orbital energy level of PhCZ is the highest, and that of 2Br2CZ is the lowest. The crystals of PhCZ, 1Br1CZ, and 2Br2CZ are monoclinic, orthorhombic, and triclinic system, which exhibit room temperature phosphorescence with lifetimes of 171.81, 37.15, and 28.77 ms, and their corresponding phosphorescence quantum yields are 0.83%, 0.16%, and 4.58%. It theoretically reveals that six triplet energy levels (T1-T6) exist under S1 in 2Br2CZ crystal, and the spin orbit coupling constants between S1 and Tn in 2Br2CZ are also greater than those in PhCZ and 1Br1CZ, which promotes the intersystem crossing. Meanwhile, through crystal structure and Hirshfeld surface analysis, the torsion angles between the carbazole unit of 2Br2CZ and the central phenyl group reached 85.28°. The 2Br2CZ crystal exhibits the richest intermolecular interactions. A cavity of 4.498 Å is formed within the crystal skeleton of 2Br2CZ, which can precisely fixe dichloromethane with a record-high desorption temperature over 145 °C.

Synergistic Cathode Design for High-Performance Dual-Salt Magnesium/Lithium-Ion Batteries Using 2D/2D 1T/2H-MoS2@Ti3C2Tx MXene Nanocomposite.

Magnesium-ion batteries (MIBs) and dual-salt magnesium/lithium-ion batteries (MLIBs) have emerged as promising contenders for next-generation energy storage. In contrast to lithium metal anode in lithium metal batteries, magnesium metal anode in MIBs and MLIBs presents a safer alternative due to the limited dendrite growth and higher volumetric capacity, along with higher natural abundance. This study explores a MLIB configuration with a novel cathode design by employing a 2D/2D nanocomposite of 1T/2H mixed phase MoS2 and delaminated Ti3C2Tx MXene (1T/2H-MoS2@MXene) to address challenges associated with slow kinetics of magnesium ions during cathode interactions. This cathode design takes advantage of the high electrical conductivity of Ti3C2Tx MXene and the expanded interlayer spacing with enhanced conductivity of the 1T metallic phase in 1T/2H mixed phase MoS2. Through a designed synthesis method, the resulting nanocomposite cathode maintains structural integrity, enabling the stable and reversible storage of dual Mg2+ and Li+ ions. The nanocomposite cathode demonstrates superior performance in MLIBs compared to individual components (253 mAh g-1 at 50 mA g-1, and 36% of capacity retention at 1,000 mA g-1), showcasing short ion transport paths and fast ion storage kinetics. This work represents a significant advancement in cathode material design for cost-effective and safe MLIBs.

Extracellular Vesicle-Contained Thrombospondin 1 Retards Age-Related Degenerative Tendinopathy by Rejuvenating Tendon Stem/Progenitor Cell Senescence.

Advanced age is a major risk factor for age-related degenerative tendinopathy. During aging, tendon stem/progenitor cell (TSPC) function declines owing to the transition from a normal quiescent state to a senescent state. Extracellular vesicles (EVs) from young stem cells are reported to possess anti-aging functions. However, it remains unclear whether EVs from young TSPCs (TSPC-EVs) can rejuvenate senescent TSPCs to delay age-related degeneration. Here, this study finds that TSPC-EVs can mitigate the aging phenotypes of senescent TSPCs and maintain their tenogenic capacity. In vitro studies reveal that TSPC-EVs can reinstall autophagy in senescent TSPCs to alleviate cellular senescence, and that the re-establishment of autophagy is mediated by the PI3K/AKT pathway. Mechanistically, this study finds that thrombospondin 1, a negative regulator of the PI3K/AKT pathway, is enriched in TSPC-EVs and can be transported to senescent TSPCs. Moreover, in vivo studies show that the local delivery of TSPC-EVs can rejuvenate senescent TSPCs and promote their tenogenic differentiation, thereby rescuing tendon regeneration in aged rats. Taken together, TSPC-EVs as a novel cell-free approach have promising therapeutic potential for aging-related degenerative tendinopathy.

Genetic characteristics of chromosomally integrated carbapenemase gene (blaNDM-1) in isolates of Proteus mirabilis.

OBJECTIVE: This study aims to conduct an in-depth genomic analysis of a carbapenem-resistant Proteus mirabilis strain to uncover the distribution and mechanisms of its resistance genes. METHODS: The research primarily utilized whole-genome sequencing to analyze the genome of the Proteus mirabilis strain. Additionally, antibiotic susceptibility tests were conducted to evaluate the strain's sensitivity to various antibiotics, and related case information was collected to analyze the clinical distribution characteristics of the resistant strain. RESULTS: Study on bacterial strain WF3430 from a tetanus and pneumonia patient reveals resistance to multiple antibiotics due to extensive use. Whole-genome sequencing exposes a 4,045,480 bp chromosome carrying 29 antibiotic resistance genes. Two multidrug-resistant (MDR) gene regions, resembling Tn6577 and Tn6589, were identified (MDR Region 1: 64.83 Kb, MDR Region 2: 85.64 Kbp). These regions, consist of integrative and conjugative elements (ICE) structures, highlight the intricate multidrug resistance in clinical settings. CONCLUSION: This study found that a CR-PMI strain exhibits a unique mechanism for acquiring antimicrobial resistance genes, such as blaNDM-1, located on the chromosome instead of plasmids. According to the results, there is increasing complexity in the mechanisms of horizontal transmission of resistance, necessitating a comprehensive understanding and implementation of targeted control measures in both hospital and community settings.

Ethylene-mediated stomatal responses to dehydration and rehydration in seed plants.

Ethylene, a plant hormone that significantly influences both plant growth and response to stress, plays a well-established role in stress signaling. However, its impact on stomatal opening and closure during dehydration and rehydration remains relatively unexplored and is still debated. Exogenous ethylene has been proven to induce stomatal closure through a series of signaling pathways, including the accumulation of reactive oxygen species (ROS), subsequent synthesis of nitric oxide (NO) and hydrogen sulfide (H2S), and SLOW ANION CHANNEL-ASSOCIATED 1 (SLAC1) activation. Thus, it has been suggested that ethylene might function to induce stomatal closure synergistically with abscisic acid (ABA). Furthermore, it has also been shown that increased ethylene can inhibit ABA- and jasmonic acid (JA)-induced stomatal closure, thus hindering drought-induced closure during dehydration. Simultaneously, other stresses, such as chilling, ozone pollution and K+ deficiency, inhibit drought and ABA-induced stomatal closure through an ethylene synthesis dependent way. However, ethylene has been shown to take on an opposing role during rehydration, preventing stomatal opening in the absence of ABA through its own signaling pathway. These findings offer novel insights into the function of ethylene in stomatal regulation during dehydration and rehydration, gaining a better understanding of the mechanisms underlying ethylene-induced stomatal movement in seed plants.

Microbacterium salsuginis sp. nov., a halotolerant actinobacterium with antimicrobial activity.

A novel Gram-staining-positive actinobacterium with antimicrobial activity, designated CFH 90308T, was isolated from the sediment of a salt lake in Yuncheng, Shanxi, south-western China. The isolate exhibited the highest 16S rRNA gene sequence similarities to Microbacterium yannicii G72T, Microbacterium hominis NBRC 15708T and Microbacterium xylanilyticum S3-ET (98.5, 98.4 and 98.2 %, respectively), and formed a separate clade with M. xylanilyticum S3-ET in phylogenetic trees. The strain grew at 15-40 ºC, pH 6.0-8.0 and could tolerate NaCl up to a concentration of 15 % (w/v). The whole genome of strain CFH 90308T consisted of 4.33 Mbp and the DNA G+C content was 69.6 mol%. The acyl type of the peptidoglycan was glycolyl and the whole-cell sugars were galactose and mannose. The cell-wall peptidoglycan mainly contained alanine, glycine and lysine. The menaquinones of strain CFH 90308T were MK-12, MK-13 and MK-11. Strain CFH 90308T contained anteiso-C15:0, anteiso-C17:0, iso-C16:0 and iso-C15:0 as the predominant fatty acids. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between CFH 90308T and the other species of the genus Microbacterium were found to be low (ANIb <81.3 %, dDDH <25.6 %). The secondary metabolite produced by strain CFH 90308T showed antibacterial activities against Bacillus subtilis, Pseudomonas syringae, Aeromonas hydrophila and methicillin-resistant Staphylococcus aureus. Based on genotypic, phenotypic and chemotaxonomic results, the isolate is considered to represent a novel species of the genus Microbacterium, for which the name Microbacterium salsuginis sp. nov. is proposed. The type strain is CFH 90308T (=DSM 105964T=KCTC 49052T).

Fibroblast growth factor receptor 4 deficiency in macrophages aggravates experimental colitis by promoting M1-polarization.

OBJECTIVE AND DESIGN: Compelling evidence indicates that dysregulated macrophages may play a key role in driving inflammation in inflammatory bowel disease (IBD). Fibroblast growth factor (FGF)-19, which is secreted by ileal enterocytes in response to bile acids, has been found to be significantly lower in IBD patients compared to healthy individuals, and is negatively correlated with the severity of diarrhea. This study aims to explore the potential impact of FGF19 signaling on macrophage polarization and its involvement in the pathogenesis of IBD. METHODS: The dextran sulfate sodium (DSS)-induced mouse colitis model was utilized to replicate the pathology of human IBD. Mice were created with a conditional knockout of FGFR4 (a specific receptor of FGF19) in myeloid cells, as well as mice that overexpressing FGF19 specifically in the liver. The severity of colitis was measured using the disease activity index (DAI) and histopathological staining. Various techniques such as Western Blotting, quantitative PCR, flow cytometry, and ELISA were employed to assess polarization and the expression of inflammatory genes. RESULTS: Myeloid-specific FGFR4 deficiency exacerbated colitis in the DSS mouse model. Deletion or inhibition of FGFR4 in bone marrow-derived macrophages (BMDMs) skewed macrophages towards M1 polarization. Analysis of transcriptome sequencing data revealed that FGFR4 deletion in macrophages significantly increased the activity of the complement pathway, leading to an enhanced inflammatory response triggered by LPS. Mechanistically, FGFR4-knockout in macrophages promoted complement activation and inflammatory response by upregulating the nuclear factor-κB (NF-κB)-pentraxin3 (PTX3) pathway. Additionally, FGF19 suppressed these pathways and reduced inflammatory response by activating FGFR4 in inflammatory macrophages. Liver-specific overexpression of FGF19 also mitigated inflammatory responses induced by DSS in vivo. CONCLUSION: Our study highlights the significance of FGF19-FGFR4 signaling in macrophage polarization and the pathogenesis of IBD, offering a potential new therapeutic target for IBD.

Post-transfusion severe headache in a patient with thalassemia with superficial siderosis of the central nervous system: a case report and literature review.

BACKGROUND: Patients with severe thalassemia may experience adverse effects from transfusion such as fever, rash, and iron overload after long-term transfusion therapy. Severe headaches as a side effect of blood transfusion in patients with thalassemia are not commonly observed, especially when combined with superficial siderosis of the central nervous system, which is easily misdiagnosed and requires excessive examination and treatment. CASE PRESENTATION: A 31-year-old woman was admitted with severe headache and vomiting over 3 days following blood transfusion. She was diagnosed with intermediate α-thalassemia at 2 years of age and had a history of irregular blood transfusions. Physical examination revealed horizontal nystagmus with no other abnormal neurological signs. Magnetic resonance (MR) imaging, MR venography, MR arteriography, and cerebrospinal fluid analysis were normal. However, susceptibility-weighted imaging showed abnormal signals in the bilateral and fourth ventricles. Initial antibiotics, antivirals, decompression of intracranial pressure, iron chelation, and symptomatic treatments were administered; subsequently, small intermittent blood transfusions were cautiously administered for severe anemia. The patient's headache was gradually relieved, and she was discharged on day 9. At the 5-month follow-up, the patient's headache recurred following another transfusion. CONCLUSIONS: Severe post-transfusion headache in patients with thalassemia has not been fully recognized and is easily misdiagnosed, leading to excessive examination and treatment. Understanding the clinical features of transfusion-related headaches can help identify this complication, but the exact pathophysiological mechanism requires further research.

Chromosome level genome assembly and transcriptome analysis of E11 cells infected by tilapia lake virus.

The E11 cell line, derived from striped snakehead fish (Channa striata), possesses a distinctive feature: it is persistently infected with a C-type retrovirus. Notably, it exhibits high permissiveness to piscine nodavirus and the emerging tilapia lake virus (TiLV). Despite its popularity in TiLV research, the absence of genome assembly for the E11 cell line and Channa striata has constrained research on host-virus interactions. This study aimed to fill this gap by sequencing, assembling, and annotating the E11 cell line genome. Our efforts yielded a 600.5 Mb genome including 24 chromosomes with a BUSCO score of 98.8%. In addition, the complete proviral DNA sequence of snakehead retrovirus (SnRV) was identified in the E11 cell genome. Comparative genomic analysis between the E11 cell line and another snakehead species Channa argus revealed the loss of many immune-related gene families in the E11 cell genome, indicating a compromised immune response. We also conducted transcriptome analysis of mock- and TiLV-infected E11 cells, unveiling new perspectives on virus-virus and host-virus interactions. The TiLV infection suppressed the high expression of SnRV in E11 cells, and activated some other endogenous retroviruses. The protein-coding gene comparison revealed a pronounced up-regulation of genes involved in immune response, alongside a down-regulation of genes associated with specific metabolic processes. In summary, the genome assembly and annotation of the E11 cell line provide valuable resources to understand the SnRV and facilitate further studies on nodavirus and TiLV. The RNA-seq profiles shed light on the cellular mechanisms employed by fish cells in response to viral challenges, potentially guiding the development of therapeutic strategies against TiLV in aquaculture. This study also provides the first insights into the viral transcriptome profiles of endogenous SnRV and evading TiLV, enhancing our understanding of host-virus interactions in fish.

Clopidogrel with indobufen or aspirin in minor ischemic stroke or high-risk transient ischemic attack: a randomized controlled clinical study.

BACKGROUND: Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. OBJECTIVE: The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. METHODS: An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset. RESULTS: We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874-7.036, P < 0.0001). Although the improvement rate of NIHSS score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). CONCLUSION: The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).

Rainfall-induced changes in aquatic microbial communities and stability of dissolved organic matter: Insight from a Fen river analysis.

Microbial communities are pivotal in aquatic ecosystems, as they affect water quality, energy dynamics, nutrient cycling, and hydrological stability. This study explored the effects of rainfall on hydrological and photosynthetic parameters, microbial composition, and functional gene profiles in the Fen River. Our results demonstrated that rainfall-induced decreases in stream temperature, dissolved oxygen, pH, total phosphorus, chemical oxygen demand, and dissolved organic carbon concentrations. In contrast, rainfall increased total dissolved solids, salinity, and ammonia-nitrogen concentrations. A detailed microbial community structure analysis revealed that Cyanobacteria was the dominant microbial taxon in the Fen River, accounting for approximately 75% and 25% of the microalgal and bacterial communities, respectively. The abundance of Chlorophyta and Bacillariophyta increased by 47.66% and 29.92%, respectively, whereas the relative abundance of Bacteroidetes decreased by 37.55% under rainfall conditions. Stochastic processes predominantly affected the assembly of the bacterial community on rainy days. Functional gene analysis revealed variations in bacterial functions between sunny (Sun) and rainy (Rain) conditions, particularly in genes associated with the carbon cycle. The 3-oxoacyl-[acyl-carrier-protein] reductase gene was more abundant in the Fen River bacterial community. Particular genes involved in metabolism and environmental information processing, including the acetyl-CoA C-acetyltransferase (atoB), enoyl-CoA hydratase (paaF), and branched-chain amino acid transport system gene (livK), which are integral to environmental information processing, were more abundant in Sun than the Rain conditions. In contrast, the phosphate transport system gene, the galactose metabolic gene, and the pyruvate metabolic gene were more abundant in Rain. The excitation-emission matrix analysis with parallel factor analysis identified four fluorescence components (C1-C4) in the river, which were predominantly protein- (C1) and humic-like (C2-C4) substances. Rainfall affected organic matter production and transport, leading to changes in the degradation and stability of dissolved organic matter. Overall, this study offers insight into how rainfall affects aquatic ecosystems.

Leisure-time physical activity and the incidence of atrial fibrillation in senior adults: a prospective cohort study.

OBJECTIVE: Whether physical activity could reduce the risk of atrial fibrillation (AF) remains unclear. This study was to investigate the relationship of leisure-time physical activity (LTPA) with AF incidence among Chinese older adults. METHODS: A total of 3253 participants aged ≥60 years from the Guangzhou Heart Study were successfully followed between March 2018 and September 2019. LTPA was assessed using a modified Global Physical Activity Questionnaire. AF was ascertained by 12-lead electrocardiograms, 24-hour single-lead Holter and clinical examination. The Cox proportional hazards model was used to the estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for confounders, and the population-attributable fraction (PAF) was estimated. RESULTS: A total of 76 (2.34%) new-onset cases of AF were identified during a median of 31.13 months of follow-up. After adjustment for confounders, subjects who had LTPA at least 10.0 metabolic equivalent (MET)-hours/week had a 55% lower risk of developing AF (HR: 0.45, 95%CI: 0.25-0.81), and at least 20 MET-hours/week reduced the risk by 45% (HR: 0.55, 95%CI: 0.34-0.92). At least 11% (PAF: 11%, 95%CI: 0%-20%) or 14% (PAF: 14%, 95%CI: 0%-26%) of AF cases could be avoided, respectively, if the subjects do LTPA at least 10 MET-hours/week or 20 MET-hours/week. A significant exposure-response trend was also observed between LTPA and AF risk (Plinear-trend = 0.002). For a specific LTPA, doing housework was associated with a 43% reduced risk, while engaging in ball games was associated with an increased risk. CONCLUSION: This prospective cohort study indicated that a higher LTPA volume was associated with a lower AF risk in Chinese older adults.

Long-term outcomes of endoscopic or surgical resection in T1 colorectal cancer patients: a retrospective cohort study.

BACKGROUND: The personalized treatments of T1 colorectal cancer (CRC) remains controversial. We compared the long-term outcomes of T1 CRC patients after endoscopic resection (ER) and surgery, and evaluated the risk factors for the long-term prognosis. METHODS: T1 CRCs after resection at the Cancer Hospital, Chines Academy of Medical Sciences from June 2011 to November 2021 were reviewed. High-risk factors included positive resection margin, poor differentiation, deep submucosal invasion (DSI ≥ 1000 µm), lymphovascular invasion and intermediate/high tumor budding. Comparative analyses were conducted based on three treatment methods: follow-up after ER (Group A), additional surgery after ER (Group B) and initial surgery (Group C). The primary endpoints included recurrence-free survival (RFS) and overall survival (OS). Cox proportional hazard regression models were constructed to identify risk factors for RFS and OS. RESULTS: A total of 528 patients were enrolled (173 patients in Group A, 102 patients in Group B, 253 patients in Group C). The 3-year RFS, 5-year RFS, 3-year OS, and 5-year OS rates were 96.7%, 94.7%, 99.1%, and 97.8%, respectively. In the absence of other high-risk factors, RFS (P = 0.321) and OS (P = 0.155) of patients with DSI after ER were not inferior to those after surgery. Multivariate analyses identified sex (HR 0.379; 95% CI 0.160-0.894), Charlson comorbidities index (CCI) (HR 3.330; 95% CI 1.571-7.062), margin (HR 8.212; 95% CI 2.325-29.006), and budding (HR 3.794; 95% CI 1.686-8.541) as independent predictive factors of RFS, and identified CCI (HR 10.266; 95% CI 2.856-36.899) as an independent predictive factor of OS. CONCLUSION: The long-term outcomes of ER are comparable to those of surgery in T1 CRC patients with DSI when other high-risk factors are negative. Resection margin, tumor budding, sex, and CCI may be the most important long-term prognostic factors for T1 CRC patients.

Differences in the prevalence of allergy and asthma among US children and adolescents during and before the COVID-19 pandemic.

BACKGROUND: The increasing prevalence of allergies and asthma has led to a growing global socioeconomic burden. Since the outbreak of the COVID-19 pandemic, the health and lifestyles of children and adolescents have changed dramatically. It's unclear how this shift impacted allergy and asthma, with limited studies addressing this question. We aim to explore the difference of the prevalence of allergies and asthma among US children and adolescents during and before the COVID-19 pandemic using a nationally representative sample of US children and adolescents. METHODS: This cross-sectional study included 31,503 participants in the National Health Interview Survey (NHIS) between 2018 and 2021. Allergies and asthma were defined on an affirmative response in the questionnaire by a parent or guardian. Chi-square tests were used to compare baseline characteristics with allergies and asthma for categorical variables. Differences in prevalence during and before the COVID-19 pandemic were estimated with weighted logistic regression, adjusting for demographic factors. Interaction analyses explored variations across strata. RESULTS: In US children and adolescents aged 0 to 17, prevalence of any allergy was 26.1% (95% CI, 24.8%- 27.4%) in 2018 and 27.1% (95% CI, 25.9%- 28.2%) in 2021. Thereinto, in 2018, prevalence of respiratory allergies, food allergies and skin allergies were 14.0% (95% CI, 13.1%- 15.0%), 6.5% (95% CI, 5.8%- 7.1%) and 12.6% (95% CI, 11.6%- 13.5%), respectively, and in 2021, 18.8% (95% CI, 17.8%- 19.9%), 5.8% (95% CI, 5.2%- 6.4%) and 10.7% (95% CI, 9.9%- 11.5%), respectively. And prevalence of asthma was 11.1% (95% CI, 10.5%- 11.7%) in 2018-2019 and 9.8% (95% CI, 9.2%- 10.4%) in 2020-2021. Prevalence of respiratory allergies, skin allergies and asthma during and before the COVID-19 pandemic in children and adolescents had statistically significant differences. The differences persisted after adjusting for demographic and socioeconomic variables. CONCLUSION: Prevalence of respiratory allergies increased and the prevalence of both skin allergies and asthma decreased among US children and adolescents during the COVID-19 pandemic compared with the pre-COVID-19 pandemic. Further research is required to explore the association between allergic diseases and the pandemic, with a particular emphasis on the impact of lifestyle changes resulting from measures to prevent COVID-19 infection.

Safety assessment of potential probiotic Lactobacillus acidophilus AM13-1 with high cholesterol-lowering capability isolated from human gut.

An important risk factor for cardiovascular disease is dyslipidemia, especially abnormal cholesterol levels. The relation between probiotics and cholesterol-lowering capability has been extensively studied. Lactobacillus acidophilus plays a significant role in affecting host health, and produces multitudinous metabolites, which have prohibitory functions against pathogenic microorganisms. In this study, we identified a cholesterol-lowering strain AM13-1, isolated from a fecal sample obtained from a healthy adult male, and performed comprehensive function analysis by whole-genome analysis and in vitro experiments. Genome analyses of L. acidophilus AM13-1 revealed that carbohydrate and amino acid transport, metabolism, translation, ribosomal structure, and biogenesis are abundant categories of functional genes. No virulence factors or toxin genes with experimentally verified were found in the genome of strain AM13-1. Besides, plenty of probiotic-related genes were predicted from the L. acidophilus AM13-1 genome, such as cbh, atpA-D, and dltD, with functions related to cholesterol-lowering and acid resistance. And strain AM13-1 showed high-efficiency of bile salt hydrolase activity and the capacity for removing cholesterol with efficiency rates of 70%. These function properties indicate that strain AM13-1 can be considered as a probiotic candidate for use in food and health care products.

Medium-intensity statin with ezetimibe versus high-intensity statin in acute ischemic cerebrovascular disease (MESIA): A randomized clinical trial.

BACKGROUND: High-risk stroke patients are recommended to receive high-intensity statin therapy to reduce the risk of stroke recurrence. However, doubling the dosage of statin drugs did not increase the achievement rate of LDL-C target or provide additional clinical benefits, but significantly increased the risk of adverse reactions. Statins and ezetimibe work through different mechanisms and the combined use of statins and ezetimibe significantly improves outcomes with comparable safety profiles. We tested the hypothesis that moderate-intensity statin with ezetimibe may offer advantages over the conventional high-intensity statin regimen in terms of efficacy and safety. METHODS: We conducted a randomized controlled trial. Eligible participants were aged 18 years or older with acute ischemic cerebrovascular disease. We randomly assigned (1:1) participants within the acute phase of ischemic stroke, i.e., within 1 week after the onset of mild ischemic stroke (NIHSS score ≤ 5), within 1 month for severe cases (NIHSS score ≥ 16), and within 2 weeks for the rest, as well as patients with TIA within 1 week of symptom onset, to receive either moderate-intensity statin with ezetimibe (either 10-20 mg atorvastatin calcium tablets plus a 10 mg ezetimibe tablet, or 5-10 mg rosuvastatin calcium tablets once per day plus a 10 mg ezetimibe tablet once per day) or high-intensity statin (40 mg atorvastatin calcium tablets or 20 mg rosuvastatin calcium tablets once per day) for 3 months. Randomization was performed using a random number table method. The primary efficacy outcome was the level and achievement rate of LDL-C after 3 months of treatment, specifically LDL-C ≤ 1.8 mmol/L or a reduction in LDL-C ≥ 50 %. The secondary outcome was the incidence of new stroke or transient ischemic attack (TIA) within 3 months. The safety outcome was liver and renal function tests, and the occurrence of statin-related muscle events within 3 months. FINDINGS: This trial took place between March 15, 2022, and March 7, 2023. Among 382 patients screened, 150 patients were randomly assigned to receive either medium-intensity statins with ezetimibe (n = 75) or high-intensity statins (n = 75). Median age was 60.0 years (IQR 52.75-70.25); 49 (36.6 %) were women and 85 (63.4 %) were men. The target achievement of LDL-C at 3 months occurred in 62 (89.86 %) of 69 patients in the medium-intensity statin with ezetimibe group and 46 (70.77 %) of 65 patients in the high-intensity statin group (P=0.005, OR=0.273, 95 % CI: 0.106, 0.705). The reduction magnitude of LDL-C in moderate-intensity statin with ezetimibe group was significantly higher (-56.540 % vs -47.995 %, P=0.001). Moderate-intensity statin with ezetimibe group showing a trend of a greater reduction in LDL-C absolute value than high-intensity statin group but without statistical significance (-1.77±0.90 vs -1.50±0.89, P=0.077). New AIS or TIA within 3 months, liver and renal function tests, and the occurrence of statin-related muscle events within 3 months were also statistically insignificant. Multivariate logistic regression analysis showed that both gender and lipid-lowering regimen as independent risk factors influencing the rate of LDL-C achievement in individuals diagnosed with acute ischemic cerebrovascular disease, but only lipid-lowering regimen had predictive value. INTERPRETATION: Compared to guideline-recommended high-intensity statin therapy, moderate-intensity statin with ezetimibe further improved the achievement rate of LDL-C in patients with acute ischemic cerebrovascular disease, with a higher reduction magnitude in LDL-C. In terms of safety, there was no significant difference between the two regimens, suggesting that moderate-intensity statin with ezetimibe can also be considered as an initial treatment option for patients with acute ischemic cerebrovascular disease.

Aggregation Behavior and Application Properties of Novel Glycosylamide Quaternary Ammonium Salts in Aqueous Solution.

Amidation of lactobionic acid with N,N-dimethylaminopropyltriamine was conducted to obtain N-(3'-dimethylaminopropyl)-lactamido-3-aminopropane (DDLPD), which was quaternized with bromoalkanes of different carbon chain lengths to synthesize double-stranded lactosylamide quaternary ammonium salt N-[N'[3-(lactosylamide)]propyl-N'-alkyl] propyl-N,N-dimethyl-N-alkylammonium bromide (CnDDLPB, n = 8, 10, 12, 14, 16). The surface activity and the adsorption and aggregation behaviors of the surfactants were investigated via equilibrium surface tension, dynamic light scattering, and cryo-electron microscopy measurements in an aqueous solution. The application properties of the products in terms of wettability, emulsification, foam properties, antistatic, salt resistance, and bacteriostatic properties were tested. CnDDLPB exhibited a low equilibrium surface tension of 27.82 mN/m. With an increase in the carbon chain length, the critical micellar concentration of CnDDLPBD decreased. Cryo-electron microscopy revealed that all products except C8DDLPB formed stable monolayer, multi-layer, and multi-compartmental vesicle structures in an aqueous solution. C14DDLPB has the best emulsification performance on soybean oil, with a time of 16.6 min; C14DDLPB has good wetting and spreading properties on polytetrafluoroethylene (PTFE) when the length of carbon chain is from 8 to 14, and the contact angle can be lowered to 33°~40°; CnDDLPB has low foam, which is typical of low-foaming products; C8DDLPB and C10DDLPB both show good antistatic properties. C8DDLPB and C14DDLPB have good salt resistance, and C12DDLPB has the best antimicrobial property, with the inhibition rate of 99.29% and 95.28% for E. coli and Gluconococcus aureus, respectively, at a concentration of 350 ppm.

Blade-Coating (100)-Oriented α-FAPbI3 Perovskite Films via Crystal Surface Energy Regulation for Efficient and Stable Inverted Perovskite Photovoltaics.

Photoactive black-phase formamidinium lead triiodide (α-FAPbI3) perovskite has dominated the prevailing high-performance perovskite solar cells (PSCs), normally for those spin-coated, conventional n-i-p structured devices. Unfortunately, α-FAPbI3 has not been made full use of its advantages in inverted p-i-n structured PSCs fabricated via blade-coating techniques owing to uncontrollable crystallization kinetics and complicated phase evolution of FAPbI3 perovskites during film formation. Herein, a customized crystal surface energy regulation strategy has been innovatively developed by incorporating 0.5 mol % of N-aminoethylpiperazine hydroiodide (NAPI) additive into α-FAPbI3 crystal-derived perovskite ink, which enabled the formation of highly-oriented α-FAPbI3 films. We deciphered the phase transformation mechanisms and crystallization kinetics of blade-coated α-FAPbI3 perovskite films via combining a series of in-situ characterizations and theoretical calculations. Interestingly, the strong chemical interactions between the NAPI and inorganic Pb-I framework help to reduce the surface energy of (100) crystal plane by 42 %, retard the crystallization rate and lower the formation energy of α-FAPbI3. Benefited from multifaceted advantages of promoted charge extraction and suppressed non-radiative recombination, the resultant blade-coated inverted PSCs based on (100)-oriented α-FAPbI3 perovskite films realized promising efficiencies up to 24.16 % (~26.5 % higher than that of the randomly-oriented counterparts), accompanied by improved operational stability. This result represented one of the best performances reported to date for FAPbI3-based inverted PSCs fabricated via scalable deposition methods.