Polar and quasicrystal vortex observed in twisted-bilayer molybdenum disulfide.

We report the observation of an electric field in twisted-bilayer molybdenum disulfide (MoS2) and elucidate its correlation with local polar domains using four-dimensional scanning transmission electron microscopy (4D-STEM) and first-principles calculations. We reveal the emergence of in-plane topological vortices within the periodic moiré patterns for both commensurate structures at small twist angles and the incommensurate quasicrystal structure that occurs at a 30° twist. The large-angle twist leads to mosaic chiral vortex patterns with tunable characteristics. A twisted quasicrystal bilayer, characterized by its 12-fold rotational symmetry, hosts complex vortex patterns and can be manipulated by picometer-scale interlayer displacement. Our findings highlight that twisting 2D bilayers is a versatile strategy for tailoring local electric polar vortices.

Detoxification effect of sodium thiosulfate on cadmium poisoning in Litopenaeus vannamei and the mechanisms of intestinal flora regulation.

Cadmium (Cd) is currently one of the heavy metals with the highest environmental toxicity impact. Sodium thiosulfate (Na2S2O3) is a commonly used heavy metal detoxification drug in clinical practice, however, it has not been used for Cd detoxification of Litopenaeus vannamei. The present study used exposure of L. vannamei to 150 µg/L of Cd while mitigating in the addition of 75 µg/L of Na2S2O3 for 28 days. The goal was to study the detoxifying effect of Na2S2O3 on L. vannamei poisoning and its role in intestinal flora. The results showed that the growth of Cd group was inhibited, and the growth rate and weight gain of Cd + ST group were greater than that of Cd group. The function and structure of L. vannamei intestinal microorganisms were significantly changed under Cd stress. This work reveals that Na2S2O3 can mitigate the damage caused by this concentration to L. vannamei to a certain extent.

Comprehensive analysis of multiple regulated cell death risk signatures in lung adenocarcinoma.

Background: Regulated cell death (RCD) has considerable impact on tumor progress and sensitivity of treatment. Lung adenocarcinoma (LUAD) show a high resistance for conventional radiotherapies and chemotherapies. Currently, regulation of cancer cell death has been emerging as a new promising therapeutic avenue for LUAD patients. However, the crosstalk in each pattern RCD is unclear. Methods: We integrated collected the hub-genes of 12 RCD subroutines and compressively analyzed these hub-genes synergistic effect in LUAD. The characters of RCD genes expression and prognosis were developed in The Cancer Genome Atlas (TCGA)-LUAD data. We developed and validated an RCD risk model based on TCGA and GSE70294 data set, respectively. Functional annotation and tumor immunotherapy based on the risk model were also investigated. Results: 28 RCD-related genes and two LUAD molecular cluster were identified. Survival analysis revealed that the prognosis in high-risk group was worser than those in low-risk group. Functional enrichment analysis indicated that the RCD risk model correlated with immune responses. Further analysis indicated that the high-risk group in RCD risk model exhibited an immunosuppressive microenvironment and a lowly immunotherapy responder ratio. Conclusions: We present an RCD risk model which have a promising ability in predicting LUAD prognosis and immunotherapy response.

Tracheobronchomegaly associated with tracheobronchopathia osteochondroplastica: a case report.

Tracheobronchomegaly (TBM) is a rare condition characterized by the dilatation of the trachea and bronchi due to severe atrophy of elastic fibers, accompanied by the thinning of the muscularis mucosae and the development of diverticula between cartilaginous rings. The etiology of this condition remains unclear. Tracheobronchopathia osteochondroplastica (TO) is another uncommon airway disease with an unknown etiology. The co-occurrence of these two diseases has not been reported. In this study, we report and discuss a case involving an elderly man with TBM and TO with a history of recurrent pneumonia over the past 6 years.

Long-Term Resistance to Phase Change-Induced Wetting Transition on Biphilic Armored Superhydrophobic Surfaces.

Material surfaces maintaining a liquid super-repellent is crucial in fields such as anti-fouling, drag reduction, and heat transfer. Superhydrophobic surfaces provide an effective approach but suffer from phase change-induced wetting transitions, hindering their practical applications. In this work, Biphilic armored superhydrophobic surfaces (BASS) are designed by integrating hydrophilic interconnected surface frames with superhydrophobic nanostructures. The hydrophilic top of the frame provides spatial selectivity for condensate droplet nucleation, and superhydrophobic nanostructures enable staying dry. Further growth, coalescence, jumping, and roll-off of the condensate droplets on BASS, show remarkable resistance to phase change-induced wetting transition. It still maintains stable superhydrophobicity when exposed to 100 °C of steam for 240 h, at least two orders of magnitude improvement over traditional superhydrophobic surfaces. Such a designing BASS provides an effective approach to address the phase change-induced wetting transition, thereby extending the practical application in the fields of condensation heat transfer, anti-fouling, and fluid transportation of superhydrophobic surfaces.

Willow catkin template synthesis of NiS@NSC hollow tubes for highly sensitive dual-function electrochemical detection of acetaminophen and Cu2.

Public health and environmental well-being have become increasingly threatened by the contamination of pharmaceuticals and heavy metal ions. This study focuses on addressing this critical issue by developing a novel electrochemical sensor for the dual-functional detection of acetaminophen (AP) and Cu2+. Utilizing willow catkins as a biomass template, a hollow tubular NiS@NSC composite was prepared by simple nickel salt impregnation combined with calcination and sulfurization. A highly sensitive dual-functional electrochemical sensor was thus constructed that can detect both acetaminophen (AP) and Cu2+. By examining its electrochemical properties, the sensor achieves an impressive detection limit of 1.33 pM for AP, with a linear range of 4.00 pM ~ 0.15 mM. The sensor can also detect Cu2+, with a detection limit of 1.04 µM, and a linear range of 3.13 µM ~ 0.66 mM. The sensor also exhibits strong resistance to interference, and good repeatability and stability. In addition, the sensor has demonstrated good performance in actual sample analysis, including the detection of AP in serum and Cu2+ in wastewater. This excellent electrochemical sensing performance is mainly attributed to the synergistic effect of its unique tubular structure and highly conductive N, S co-doped carbon. This results in the sensor exhibiting minimal charge transfer resistance, an extensive electrochemically active surface area, and a high density of active sites.

A bibliometric analysis of Oropouche virus.

Objectives: Oropouche virus (OROV) causes systemic infections including the nervous and blood systems, posing a significant and growing public health challenge. However, a comprehensive review of the bibliometric analysis of OROV is still lacking. Therefore, the objective of this study was to provide insight into the research dynamics and current hotspots of OROV. Methods: This study used bibliometric analysis to explore the current status of research related to OROV. 148 publications from 1961 to 2024 were retrieved from the Scopus database. Countries, authors, institutions, journals, references, and keywords were visualized using VOSviewer, CiteSpace, R studio, and Bibliometrix. Microsoft Excel was used for statistical analysis. Results: Brazil is the country with the highest number of publications, total cited frequency, and the most extensive international collaboration. The most popular journal in this field is the American Journal of Tropical Medicine and Hygiene. Instituto Evandro Chagas is the institution with the highest number of publications, and Eurico Arruda is involved in the highest number of publications. Keyword co-occurrence analysis showed that Oropouche bunyavirus, virology, bunyavirus, priority journal, and nucleotide sequence are the main research hotspots in this field. Conclusion: Our study provides a comprehensive overview of the research trends and key areas of focus in OROV. The field is currently experiencing rapid growth, as evidenced by the rising number of annual publications, which not only highlights increased research activity but also lays a solid foundation for further in-depth investigations. This trend offers valuable insights for developing effective strategies for outbreak prevention and control in public health. Presently, researchers are concentrating on the detailed study of Bunyavirus infections, employing both virological and genetic approaches to elucidate their complex pathogenic mechanisms.

Corrigendum to "Gene mutations in newly diagnosed multiple myeloma patients detected by next-generation sequencing technology" [Cancer Pathog Ther. 2024;2:205-211].

[This corrects the article DOI: 10.1016/j.cpt.2023.12.004.].

Adipokine/hepatokines profiling of fatty liver in adolescents and young adults: cross-sectional and prospective analyses of the BCAMS study.

OBJECTIVE: The underlying connections between obesity and non-alcoholic fatty liver disease (NAFLD) are not fully understood. One potential link might be the imbalanced adipokines and hepatokines. We aimed to explore the associations between specific adipokines/hepatokines and NAFLD in Chinese youth and to determine how these biomarkers mediate the obesity-NAFLD relationship. METHODS: We analyzed data from the 10-year follow-up visit of the Beijing Children and Adolescents Metabolic Syndrome (BCAMS) study (n = 509; mean age = 20.2 years) for a comprehensive metabolic risk assessment, including liver ultrasound and plasma measurements of adiponectin, leptin, fibroblast growth factor 21 (FGF21), retinol-binding protein 4 (RBP4), and angiopoietin-like protein 8 (ANGPTL8). Longitudinal analysis was performed on a subgroup (n = 307), with complete baseline (mean age = 12.2 years) and follow-up data. Mediation models assessed how obesity at baseline and follow-up influence NAFLD through these biomarkers. RESULTS: Participants with NAFLD exhibited a high prevalence of central obesity (90.9%). Both cross-sectional and prospective analyses identified increased RBP4, FGF21, leptin, and decreased adiponectin levels as significant predictors of NAFLD. More adipokine/hepatokine abnormalities were linked to higher NAFLD risk. Furthermore, ratios reflecting adipokine/hepatokine imbalances, including leptin/adiponectin, FGF21/adiponectin, and RBP4/adiponectin, demonstrated stepwise changes correlating with NAFLD severity (all p < 0.05). Mediation analysis indicated that these four adipokines/hepatokines accounted for approximately 72.4% of the central obesity-NAFLD relationship and 80.1% in the subgroup analysis using baseline childhood data. CONCLUSIONS: Dysregulated adipokines/hepatokines may explain the onset or progression of obesity-related NAFLD in youths. Higher RBP4, FGF21 and leptin, alongside lower adiponectin, could serve as early biomarkers for NAFLD.

A dual-STING-activating nanosystem expands cancer immunotherapeutic temporal window.

Stimulator of interferon genes (STING) is a promising antitumor target via bridging innate and adaptive immunity, yet the transient nature of immune signal transduction renders small-molecule agonists susceptible to short time effectiveness. Here, we report a dual-STING-activating micelle system (D-SAM) to dynamically program STING kinetics. Mechanistically, the natural ligand cGAMP encapsulated in D-SAM initiates STING signaling, while the pH-sensitive polymeric agonist PC7A disassembled from micelle shell buffers lysosomal protons and retards STING degradation. This prolonged STING activity facilitates dendritic cell (DC) antigen presentation and extends cytotoxic T lymphocyte priming. D-SAM improves efficacy over single soluble or delivered agonists against established, metastatic, and recurring murine tumors. Specific depletion of STING in DCs or blockade of CD8+ T cell infiltration abrogates therapeutic effects. The feasibility of immune modulation is further validated in resected human patient tissues. This work underscores the temporal rhythm of STING as crucial for mounting a potent and enduring antitumor immune response.

Efficacy and Safety of Evolocumab and Alirocumab as PCSK9 Inhibitors in Pediatric Patients with Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis.

Background and Objectives: The proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab are recently developed promising drugs used for treatment of familial hypercholesterolemia (FH). This systematic review and meta-analysis aimed to thoroughly evaluate the efficacy and safety of evolocumab and alirocumab among pediatric patients with FH. Materials and Methods: A comprehensive search was conducted in PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov from inception through July 2024 to identify primary interventional studies among pediatric patients with FH. Meta-analyses were performed if appropriate. Statistics were analyzed using Review Manager version 5.4 and Stata version 16.0. Results: Fourteen articles reporting nine unique studies were included. There were three randomized controlled trials (RCTs) assessing evolocumab or alirocumab involving a total of 320 pediatric patients, one cross-over trial and five single-arm or observational studies. Pooled results showed significant efficacy of evolocumab/alirocumab in reducing low-density lipoprotein cholesterol (LDL-C) (weighted mean difference [WMD]: -37.92%, 95% confidence interval [CI]: -43.06% to -32.78%; I2 = 0.0%, p = 0.60), apolipoprotein B (WMD: -33.67%, 95% CI: -38.12% to -29.22%; I2 = 0.0%, p = 0.71), and also lipoprotein(a) (WMD: -16.94%, 95% CI: -26.20% to -7.69%; I2 = 0.0%, p = 0.71) among pediatric patients with FH. The efficacies of evolocumab/alirocumab on LDL-C reduction within pediatric patients with heterozygous FH (HeFH) were consistent between studies, whereas in patients with homozygous FH (HoFH), it varied dramatically. Pediatric patients with the null/null variant may respond to the treatment. PCSK9 inhibitors were generally well tolerated within most pediatric patients, in line with previous studies among adult populations. Conclusions: The PCSK9 inhibitors evolocumab/alirocumab significantly reduced LDL-C and some other lipid parameters, such as apolipoprotein B, in pediatric patients with HeFH. These drugs may be appropriate as a potential therapy for pediatric patients with HoFH who cannot achieve LDL-C targets with other treatments. Evolocumab/alirocumab was generally well tolerated in the pediatric population.

A splicing isoform of PD-1 promotes tumor progression as a potential immune checkpoint.

The immune checkpoint receptor, programmed cell death 1 (PD-1, encoded by PDCD1), mediates the immune escape of cancer, but whether PD-1 splicing isoforms contribute to this process is still unclear. Here, we identify an alternative splicing isoform of human PD-1, which carries a 28-base pairs extension retained from 5' region of intron 2 (PD-1^28), is expressed in peripheral T cells and tumor infiltrating lymphocytes. PD-1^28 expression is induced on T cells upon activation and is regulated by an RNA binding protein, TAF15. Functionally, PD-1^28 inhibits T cell proliferation, cytokine production, and tumor cell killing in vitro. In vivo, T cell-specific exogenous expression of PD-1^28 promotes tumor growth in both a syngeneic mouse tumor model and humanized NOG mice inoculated with human lung cancer cells. Our study thus demonstrates that PD-1^28 functions as an immune checkpoint, and may contribute to resistance to immune checkpoint blockade therapy.

In-depth exploration of the focus issues of TKI combined with radiotherapy for EGFR-mutant lung adenocarcinoma patients with brain metastasis: a systematic analysis based on literature metrology, meta-analysis, and real-world observational data.

BACKGROUND: There is a growing interest in utilizing a combination of brain radiotherapy (RT) and tyrosine kinase inhibitors (TKIs) for patients diagnosed with brain metastases (BM) in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LAC). The current status of this treatment strategy remains a subject of debate. METHODS: We initiated our study by conducting a comprehensive literature search using the SCI-expanded database of Web of Science Core Collection (WoSCC). We utilized the VOSPviewer software to analyze various aspects of the research, including the year of publication, authorship, keywords, and country.Subsequently, we performed an extensive and systematic literature search on popular online databases. Our primary outcome measures were overall survival (OS) and intracranial progression-free survival (iPFS), both quantified by hazard ratios (HRs). Additionally, for data verification, we included data from patients in non-small cell lung cancer with brain metastasis who underwent therapeutic intervention at the Cancer Prevention and Treatment Center of Sun Yat-sen University and the Radiotherapy Department of Hanzhong Central Hospital between August 2012 and November 2021. RESULTS: The bibliometric analysis revealed an increasing trend in research focused on the combination of RT and TKIs for the management of lung cancer brain metastases over the previous decade. Then, nine studies consistent with the research direction were included for meta-analysis. The meta-analysis showed that the OS (HR = 0.81, 95% confidence interval: 0.69-0.94; P = 0.007) and iPFS (HR = 0.71, 95% confidence interval: 0.61-0.82; P < 0.001) of the combination therapy were significantly prolonged. Finally, 168 EGFR-mutated BM advanced LAC patients in the real world were verified, and the median iPFS of the combination therapy (n = 88 and EGFR-TKIs alone (n = 80) were 16.0 and 9.0 months, respectively, (P < 0.001). The median OS was 29.0 and 27.0 months, respectively, with no dramatic difference (P = 0.188). CONCLUSIONS: Research on EGFR-mutant LAC brain metastasis has turned towards exploring optimal treatment strategies for this condition. Our meta-analysis and real-world data analysis consistently demonstrate that combination therapy offers a substantial improvement in patient survival compared to EGFR-TKI monotherapy. Notably, among patients undergoing salvage radiotherapy (RT), our subgroup analysis reveals that those initially treated with third-generation TKIs experience more significant benefits than those treated with first- or second-generation TKIs.

Natural phenol carbamates: Selective BuChE/FAAH dual inhibitors show neuroprotection in an Alzheimer's disease mouse model.

FAAH inhibition can indirectly enhance endocannabinoid signaling to therapeutic levels, effectively preventing or slowing its progression of Alzheimer's disease (AD). Hence, the search for effective dual FAAH/cholinesterase inhibitors is considerable need for disease-modifying therapies. To this aim, we designed, synthesized, and tested three series of natural phenol carbamates. The majority of carbamates proved to be potent on a single target, amongst them, compound D12 containing paeonol motif was identified as an effective dual BuChE/FAAH inhibitor, with well-balanced nanomolar activity (IC50 = 81 and 400 nM for hBuChE and hFFAH, respectively). D12 possessed BBB penetrating ability, benign safety, neuroprotection and pseudo-irreversible BuChE inhibition (Kd = 2.11 µM, k2 = 2.27 min-1), showing good drug-like properties. D12 also modulated the BV2 microglial polarization to inhibit neuroinflammation. In vivo study verified that D12 improved Aß1-41-induced learning impairments in AD mouse model for both short- and long-term memory responses. Thus, the dual activity of D12 could lead to a potentially more effective treatment for the counteraction of AD progression.

GalNAc-Conjugated siRNA Targeting Complement C3 Inhibits Osteoclast Activation in Periodontitis.

OBJECTIVE: The complement cascade plays an important role in the inflammation amplification and tissue destruction of periodontitis. Importantly, complement C3 was proved to be the central element of complement cascade. Thus, targeting inhibition of C3 has become one of the focuses of treatment method development and exploration. METHODS: The siRNAs targeting C3 were designed and screened for in vitro potency. The selected siRNA was conjugated to GalNAc (GalNAc-C3 siRNA) for liver-specific delivery. The mouse model of periodontitis was established by silk ligation. Stereomicroscopy, Micro-CT, histological and histochemical assessment, and immunofluorescence staining were performed to evaluate the level of bone destructive and osteoclast activity. The influence of GalNAc-C3 siRNA on inflammatory reactions was determined by qRT-PCR, ELISA, and flow cytometry. RESULTS: GalNAc-C3 siRNA showed great in vivo potency and durability to silence hepatic C3 mRNA expression. GalNAc-C3 siRNA treatment could effectively inhibit the production of inflammatory cytokines (IL-17A, TNF-α, IL-6, and IFN-γ) and restrain Th17 differentiation. Importantly, the expression of RANKL and differentiation of osteoclast were inhibited by GalNAc-C3 siRNA. CONCLUSION: GalNAc-C3 siRNA could efficiently play a role in bone protection by inhibiting inflammatory responses and osteoclast activities. This therapeutic siRNA may become an effective treatment strategy for periodontitis.

Causal association between insulin sensitivity index and Alzheimer's disease.

Evidence from observational and Mendelian randomization (MR) studies suggested that insulin resistance (IR) was associated with Alzheimer's disease (AD). However, the causal effects of different indicators of IR on AD remain inconsistent. Here, we aim to assess the causal association between the insulin sensitivity index (ISI), a measure of post-prandial IR, and the risk of AD. We first conducted primary and secondary univariable MR analyses. We selected 8 independent genome-wide significant (p < 5E-08, primary analyses) and 61 suggestive (p < 1E-05, secondary analyses) ISI genetic variants from large-scale genome-wide association studies (GWAS; N = 53 657), respectively, and extracted their corresponding GWAS summary statistics from AD GWAS, including IGAP2019 (N = 63 926) and FinnGen_G6_AD_WIDE (N = 412 181). We selected five univariable MR methods and used heterogeneity, horizontal pleiotropy test, and leave-one-out sensitivity analysis to confirm the stability of MR estimates. Finally, we conducted a meta-analysis to combine MR estimates from two non-overlapping AD GWAS datasets. We further performed multivariable MR (MVMR) to assess the potential mediating role of type 2 diabetes (T2D) on the association between ISI and AD using two MVMR methods. In univariable MR, utilizing 8 genetic variants in primary analyses, we found a significant causal association of genetically increased ISI with decreased risk of AD (OR = 0.79, 95% CI: 0.68-0.92, p = 0.003). Utilizing 61 genetic variants in secondary analyses, we found consistent findings of a causal effect of genetically increased ISI on the decreased risk of AD (OR = 0.89, 95% CI: 0.82-0.96, p = 0.003). Heterogeneity, horizontal pleiotropy test, and leave-one-out sensitivity analysis ensured the reliability of the MR estimates. In MVMR, we found no causal relationship between ISI and AD after adjusting for T2D (p > 0.05). We provide genetic evidence that increased ISI is significantly and causally associated with reduced risk of AD, which is mediated by T2D. These findings may inform prevention strategies directed toward IR-associated T2D and AD.

Characteristics of the vaginal microbiota and vaginal metabolites in women with cervical dysplasia.

Introduction: Emerging evidence suggests that the vaginal microbiota is closely associated with cervical cancer. However, little is known about the relationships among the vaginal microbiota, vaginal metabolites, and cervical lesion progression in women undergoing cervical dysplasia. Methods: In this study, to understand vaginal microbiota signatures and vaginal metabolite changes in women with cervical lesions of different grades and cancer, individuals with normal or cervical dysplasia were recruited and divided into healthy controls (HC) group, low-grade squamous intraepithelial lesions (LSIL) group, high-grade squamous intraepithelial lesions (HSIL) group, and cervical cancer (CC) group. Vaginal secretion samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics, and integrated analysis. Results: The results demonstrated that bacterial richness and diversity were greater in the CC group than the other three groups. Additionally, Lactobacillus was found to be negatively associated with bacterial diversity and bacterial metabolic functions, which increased with the degree of cervical lesions and cancer. Metabolomic analysis revealed that distinct metabolites were enriched in these metabolite pathways, including tryptophan metabolism, retinol metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, as well as citrate cycle (TCA cycle). Correlation analysis revealed positive associations between CC group-decreased Lactobacillus abundance and CC group-decreased metabolites. Lactobacillus iners was both negative to nadB and kynU genes, the predicted abundance of which was significantly higher in the CC group. The linear regression model showed that the combination of the vaginal microbiota and vaginal metabolites has good diagnostic performance for cervical cancer. Discussion: Our results indicated a clear difference in the vaginal microbiota and vaginal metabolites of women with cervical dysplasia. Specifically altered bacteria and metabolites were closely associated with the degree of cervical lesions and cancer, indicating the potential of the vaginal microbiota and vaginal metabolites as modifiable factors and therapeutic targets for preventing cervical cancer.

Effect and mechanism of GPR75 in metabolic dysfunction-related steatosis liver disease.

Research on G protein-coupled receptor 75 (GPR75) in metabolic dysfunction-related steatosis liver disease (MASLD) reveals its potential role in regulating body weight and energy balance. Loss-of-function mutations in the GPR75 gene are significantly associated with lower body mass index and reduced body weight. Studies demonstrate that GPR75 knockout mice exhibit lower fasting blood glucose levels, improved glucose homeostasis, and significant prevention of high-fat diet-induced MASLD. The absence of GPR75 reduces fat accumulation by beneficially altering energy balance rather than restricting adipose tissue expansion. Moreover, female GPR75 knockout mice show greater protection against lipid accumulation on a high-fat diet compared to males, potentially attributed to higher physical activity and energy expenditure. However, current research primarily relies on mouse models, and its applicability to humans requires further validation. Future studies should explore the role of GPR75 across diverse populations, its clinical potential, and delve into its specific mechanisms and interactions with other metabolic pathways. Ultimately, targeted therapies based on GPR75 could offer novel strategies for the prevention and treatment of MASLD and other metabolic disorders.