Dynamic Viral Load Monitoring and Metagenomic Sequencing in Acute Retinal Necrosis Caused by Varicella-Zoster Virus.

PURPOSE: To analyze the trend of intraocular viral load after antiviral treatment in patients with varicella-zoster virus (VZV) induced acute retinal necrosis (ARN), and to explore the effect of viral genotypes on clinical manifestations. METHODS: In this case series, viral load was detected using polymerase chain reaction from aqueous humor during treatment; viral load curves were fitted, and the time required to reach the inflection point between plateau phase and logarithmic reduction phase (Tinflection) was estimated. Variations in viral genomes were detected by metagenomic sequencing. RESULTS: Twenty eyes of 20 patients were included. The median (interquartile range) initial viral load was 5.9×107 (1.1×107-1.1×108) copies/mL. The average duration of retinitis was 5±3 weeks. The average Tinflection was 4.2±1.6 days. Tinflection was correlated with the duration of retinitis (P=0.025). Patients with VZVs carrying the p.S715* variation in ribonucleotide reductase (RNR) subunit 1 gene had lower initial viral loads (median 1.3×107 copies/ml) than those without (median 1.1×108 copies/ml; adjusted P=0.030). CONCLUSIONS: The inflection of viral load curve is helpful to estimate the length of plateau phase and the duration of retinitis during antiviral treatment in ARN patients. Loss-of-function variation in RNR gene might be correlated with lower virulence of VZV.

Synthesis of α-ketoamides via oxidative amidation of diazo compounds with O-benzoyl hydroxylamines as nitrogen source and the oxidant.

A simple, efficient method has been described for the construction of an array of α-ketoamides from readily available O-benzoyl hydroxylamines and diazo compounds as starting materials. There was a combined use of CuI as a catalyst and H2O as the oxygen source. The investigation reveals that the O-benzoyl hydroxylamines serve a dual role as both an amine source and the oxidant in this mechanism, thereby obviating the need for additional oxidants in the transformation process. This methodology could give a wider range of products in good to excellent yields for most substrates, and thus, we provide a new idea for the synthesis of α-ketoamides.

Solamargine acts as an antiviral by interacting to MZF1 and targeting the core promoter of the hepatitis B virus gene.

BACKGROUND: Hepatitis B virus (HBV) infection is still a serious threat to global health and can lead to a variety of liver diseases, including acute and chronic hepatitis, liver cirrhosis, liver failure, hepatocellular carcinoma (HCC), and so on. At present, there are mainly two kinds of drugs for the treatment of hepatitis B at home and abroad: interferon (IFN) and nucleoside/nucleotide analogs (NAs). In recent years, natural compounds have been considered an important source for the development of new anti-HBV drugs due to their complex structure, diverse components, high efficiency, and low toxicity. Many studies have demonstrated that Solamargine has significant anticancer activity, but the antiviral effect is rarely studied. This study aimed to verify the anti-HBV effect of Solamargine and to explore the specific mechanism. METHOD: The relative expression of HBV pregenomic RNA (pgRNA) was detected by reverse transcription real-time fluorescence quantitative PCR (RT-qPCR). Northern blot and western blot were used to detect the relative expression of HBV pgRNA and target protein. PCR was used in the construction of HBV pg-promoter, ENII/BCP, and a series of gene deletion mutant fluorescent reporter vectors. The fluorescence relative expression of each mutant was detected by Renilla luciferase assay. RESULTS: By binding to MZF1 (Myeloid zinc finger protein 1, MZF1), Solamargine inhibits HBV core promoter activity, reduces pregenomic RNA level, and inhibits HBV, achieving antiviral effects.

Concomitant use of antidepressants and benzodiazepines during pregnancy and associated risk of congenital malformations: a population-based cohort study in Taiwan.

BACKGROUND: Despite the frequent co-administration of antidepressants and benzodiazepines, the association between such concomitant use during pregnancy and the risk of congenital malformations remains inadequately explored. This study aims to examine the association between concomitant use of antidepressants and benzodiazepines during the first trimester and organ-specific congenital malformations. METHODS: We conducted a population-based cohort study using Taiwan's National Birth Certificate Application database, the Maternal and Child Health database, and Taiwan's National Health Insurance database. Pregnant people aged 15-50 years with singleton births between Jan 1, 2004, and Dec 31, 2018, were included. Use of antidepressants and benzodiazepines was defined as at least one prescription during the first trimester, and concomitant use was defined as the overlapping prescription of both drugs with an overlapping prescription period. The primary outcomes were overall congenital malformations and eight organ-specific malformations, consisting of the nervous system, heart, respiratory system, oral cleft, digestive system, urinary system, genital system, and limb malformations. Logistic regression models with propensity score fine stratification weighting approach were used to control for measured confounders. Analyses controlling for confounding by indication and sibling comparison analyses were done to address unmeasured confounders. No individuals with lived experience participated in the research or writing process. FINDINGS: The cohort included 2 634 021 singleton pregnancies, and 8599 (0·3%) individuals were concomitant users of antidepressants and benzodiazepines during the first trimester (mean age at delivery was 31·8 years [SD 5·2] for pregnancies with exposure to antidepressants and benzodiazepines vs 30·7 years [SD 4·9] for pregnancies without exposure). All study participants were female, and information about ethnicity was not available. Absolute risk of overall malformations was 3·81 per 100 pregnancies with exposure, compared with 2·87 per 100 pregnancies without exposure. The propensity score-weighted odds ratios (weighted ORs) did not suggest an increased risk for overall malformations (weighted OR 1·10, 95% CI 0·94-1·28), heart defects (1·01, 0·83-1·23), or any of the other organ-specific malformations, except for digestive system malformations, for which the weighted OR remained statistically significant after adjustment (1·63, 1·06-2·51). The absence of an increased risk for overall congenital malformations associated with concomitant use of antidepressants and benzodiazepines was supported by the analyses controlling for confounding by indication and sibling-matched comparisons. INTERPRETATION: The findings of this study suggest that the concomitant use of antidepressants and benzodiazepines during the first trimester is not associated with a substantial increase in risk for most malformation subtypes. However, considering other potential adverse effects of using both medications concomitantly, a thorough assessment of the risks and benefits is crucial for clinical decision making. FUNDING: National Science and Technology Council.

[Occurrence and Risk Assessment of N-nitrosamines and Their Precursors in Qingjiang River Basin].

N-nitrosamines are a type of nitrogen-containing organic pollutant with high carcinogenicity and mutagenicity. In the main drinking water sources of small and medium-sized towns in China, the contamination levels of N-nitrosamines remain unclear. In addition, there is still lack of research on the concentration of N-nitrosamines and their precursors in tributary rivers. In this study, eight N-nitrosamines and their formation potentials （FPs） were investigated in the Qingjiang River, which is a primary tributary of the Yangtze River. The sewage discharge sites were also monitored, and the environmental influencing factors, carcinogenic and ecological risks caused by N-nitrosamines, and their precursors were evaluated. The results showed that six N-nitrosamines were detected in water samples of the Qingjiang River, among which NDMA [（10 ±15） ng·L-1], NDEA [（9.3 ±9.3） ng·L-1], and NDBA [（14 ±7.8） ng·L-1] were the dominant N-nitrosamines, whereas seven N-nitrosamines were detected in chloraminated water samples, among which NDMA-FP [（46 ±21） ng·L-1], NDEA-FP [（26 ±8.3） ng·L-1], and NDBA-FP [（22 ±13） ng·L-1] were the dominant N-nitrosamine FPs. The concentrations of N-nitrosamines in the middle reaches of the Qingjiang River were higher than those in the upper and lower reaches. Furthermore, the concentrations of N-nitrosamines in the sample sites of sewage discharge and tributaries were significantly higher than those in other sampling sites. The monitoring results at the direct sewage discharge points indicated that the main source of N-nitrosamines in river water was the sewage carrying N-nitrosamines and their precursors. In addition, the concentrations of the three dominant N-nitrosamines including NDMA, NDBA, and NDEA were positively correlated with each other, mainly because of their similar sewage sources. The average carcinogenic risk to residents due to N-nitrosamine in drinking water sources was 2.4×10-5, indicating a potential carcinogenic risk. Moreover, due to the high concentrations of N-nitrosamine formation potentials in the Qingjiang River, the carcinogenic risk of drinking water may be even higher. The ecological risk assessment showed that the ecological risk quotient values of N-nitrosamines in the Qingjiang River watershed were lower than 0.002, which was negligible.

The biological function of demethylase ALKBH1 and its role in human diseases.

AlkB homolog 1 (ALKBH1) is a member of the AlkB family of dioxygenases that are dependent on Fe(II) and α-ketoglutarate. Mounting evidence demonstrates that ALKBH1 exhibits enzymatic activity against various substrates, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), N3-methylcytidine (m3C), 5-methylcytosine (m5C), N6-methyladenine (N6-mA, 6mA), and H2A, indicating its dual roles in different biological processes and involvement in human diseases. Up to the present, there is ongoing debate regarding ALKBH1's enzymatic activity. In this review, we present a comprehensive summary of recent research on ALKBH1, including its substrate diversity and pathological roles in a wide range of human disorders, the underlying mechanisms of its functions, and its dysregulation. We also explored the potential of ALKBH1 as a prognostic target.

Huangtu decoction alleviates chronic diarrhea of spleen-yang deficiency in mice by altering host metabolome and intestinal microbiota composition.

BACKGROUND: Huangtu decoction (HTD), a traditional Chinese medicine recipe, warms the spleen, nourishes the blood, and stops bleeding. It has been used to treat dysentery, gastrointestinal bleeding, diarrhea, and other symptoms caused by spleen-yang deficiency for more than 2,000 years in China. However, the mechanism underlying the treatment of chronic diarrhea due to spleen-yang deficiency (CDSD) using HTD remains unclear. AIMS: This study investigated whether HTD could mediate intestinal flora and serum metabolites to improve CDSD symptoms using a mouse model. METHODS: A CDSD mouse model induced by senna and an abnormal diet was constructed. The regulatory effects of HTD at 12.5, 25.0, and 50.0 g/kg/d on CDSD mice were assessed by measuring their bodyweight, diarrhea rate, loose stool rate, and histopathology. Changes in the intestinal flora of CDSD mice were analyzed by 16S rRNA gene sequencing. Untargeted serum metabolomic analysis was performed using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS). RESULTS: HTD had a modulating effect on CDSD by reducing the weight loss, diarrhea rate, loose stool rate, and pathologic damage. Intestinal flora analysis showed that HTD altered the community composition by decreasing the abundance of Allobaculum, Lactobacillus, and Ruminococcus. Serum metabolomics revealed that ascorbate and aldarate metabolism, aldosterone synthesis and secretion, platelet activation, hypoxia-inducible factor 1 signaling pathway, inositol phosphate metabolism, phosphatidylinositol signaling, galactose metabolism, and alpha-linolenic acid metabolism were modulated after HTD treatment. CONCLUSION: HTD may alleviate CDSD symptoms by reducing weight loss, diarrhea rate, loose stool rate, and pathologic damage caused by modeling and regulating intestinal flora and serum metabolites in CDSD mice.

Refined Bonded Terms in Coarse-Grained Models for Intrinsically Disordered Proteins Improve Backbone Conformations.

Coarse-grained models designed for intrinsically disordered proteins and regions (IDP/Rs) usually omit some bonded potentials (e.g., angular and dihedral potentials) as a conventional strategy to enhance backbone flexibility. However, a notable drawback of this approach is the generation of inaccurate backbone conformations. Here, we addressed this problem by introducing residue-specific angular, refined dihedral, and correction map (CMAP) potentials, derived based on the statistics from a customized coil database. These bonded potentials were integrated into the existing Mpipi model, resulting in a new model, denoted as the "Mpipi+" model. Results show that the Mpipi+ model can improve backbone conformations. More importantly, it can markedly improve the secondary structure propensity (SSP) based on the experimental chemical shift and, consequently, succeed in capturing transient secondary structures. Moreover, the Mpipi+ model preserves the liquid-liquid phase separation (LLPS) propensities of IDPs.

Decreased flow in ischemic stroke with coexisting intracranial artery stenosis and white matter hyperintensities.

Background: Stroke patients with coexisting intracranial artery stenosis (ICAS) and white matter lesions (WML) usually have a poor outcome. However, how WML affects stroke prognosis has not been determined. Objective: To investigate the quantitative forward flow at the middle cerebral artery in ICAS patients with different degrees of WML using 4D flow. Design: Single-center cross-sectional cohort study. Methods: Ischemic stroke patients with symptomatic middle cerebral artery (MCA) atherosclerosis were included, and they were divided into 2 groups based on Fazekas scale on Flair image (mild group = Fazekas 0-2, and severe group = Fazekas >2), TOF-MRA and 4D flow were performed to quantify the stenosis degree and forward flow at the proximal of stenosis. The flow parameters were compared between different white matter hyperintensity (WMH) groups, as well as in different MCA stenosis groups, logistic regression was used to validate the association between forward flow and WMH. Results: A total of 66 patients were included in this study (mean age 56 years old, 68.2% male). 77.3% of them presented with WMH (Fazekas 1-5). Comparison of flow index between mild and severe WMH groups found a significantly lower forward flow (2.34 ± 1.09 vs 3.04 ± 1.35), higher PI (0.75 ± 0.43 vs 0.66 ± 0.32), and RI (0.49 ± 0.19 vs 0.46 ± 0.15) at ipsilateral infarction MCA in the severe WMH group, all P-values <0.05. After adjusting for other covariates, forward mean flow at ipsilateral infarction MCA is still associated with severe WMH independently, OR = 0.537, 95% CI (0.294, 0.981), P = 0.043. Conclusion: Intracranial artery stenosis patients with coexisting severe WMH suffer from significantly decreased flow, which could explain the poor clinical outcome in this population, and also provide some insight into recanalization therapy in the future.

Why was the study done? stroke patients with intracranial artery stenosis (ICAS) have a high prevalence of white matter hyperintensities (WMH), a surrogate biomarker of small vessel disease (SVD), and patients with coexisting ICAS and WMH are more likely to have unfavorable clinical outcomes and higher stroke recurrence risk. However, how WMH affects stroke outcomes has been unknown. What did the researchers do? In this study, we compared the flow and perfusion index between different WMH groups, as well as in different ICAS groups using 4D flow combined with ASL, to obtain the quantitative flow relationship in this population. What did the researchers find? As a result, we found that both the degree of intracranial artery stenosis and WMH burden is associated with decreased flow, and the flow decrease is more significant at the ipsilateral of infarct. What do the findings mean? This is the first study investigating the complicated hemodynamic status using 4D flow combined with ASL in stroke patients with coexisting ICAS and WMH. The results in this study could not only provide some evidence for unfavorable clinical outcomes in ICAS patients with severe WMH burden but also give us some insight into recanalization therapy in this population.

Cardiovascular Disease, Genetic Susceptibility, and Risk of Psychiatric Disorders and Suicide Attempt: A Community-Based Matched Cohort Study Based on the UK Biobank.

BACKGROUND: The associations between cardiovascular disease (CVD) and multiple psychiatric disorders and suicide attempt, and whether different genetic susceptibilities affect such links, have not been investigated clearly. METHODS AND RESULTS: Based on the UK Biobank, we conducted a matched cohort study involving 63 923 patients who were first hospitalized with a CVD diagnosis between 1997 and 2020, and their 127 845 matched unexposed individuals. Cox models were used to examine the subsequent risk of psychiatric disorders and suicide attempt (ie, anxiety, depression, stress-related disorder, substance misuse, psychotic disorder, and suicide behaviors) following CVD. We further performed stratified analyses by polygenic risk score for each studied psychiatric condition to detect the possible effects of genetic susceptibility on the observed associations. We found an increased risk of any psychiatric disorders and suicide attempt among CVD patients, compared with matched unexposed individuals, particularly within 1 year following the CVD (fully adjusted hazard ratio [HR] within 1 year, 1.83 [95% CI, 1.58-2.12]; HR after 1 year, 1.24 [95% CI, 1.16-1.32]). By subtype, the risk elevations existed for any psychiatric disorders and suicide attempt following most categories of CVDs. Analyses stratified by polygenic risk score revealed little impact of genetic predisposition to studied psychiatric conditions on these observed links. CONCLUSIONS: Patients hospitalized for CVD were at increased subsequent risk of multiple types of psychiatric disorders and suicide attempt, especially in the first year after hospitalization, irrespective of their genetic susceptibilities to studied psychiatric conditions, and these findings underscore the necessity of developing timely psychological interventions for this vulnerable population.

Two new saponins from the rhizomes of Paris yunnanensis Franch.

The phytochemical investigation on the rhizomes of Paris yunnanensis Franch. resulted in the discovery and characterisation of six compounds, including two new saponins named parisyunnanosides M-N (1-2), and four known ones (3-6). The structures of isolated compounds were determined by spectroscopic data analysis and chemical methods. Compound 2 is a pregnane-type saponin with a special α,ß-unsaturated carboxylic acid moiety at C-17, which is first discovered in genus Paris. The anti-inflammatory activity of the isolated compounds was assessed in vitro. The results demonstrated that compounds 3 and 4 could significantly inhibit the production of NO which was induced by LPS in RAW 264.7 cells with IC50 values of 0.67 ± 0.17 µM and 0.85 ± 0.12 µM, respectively.

[Effects of Questionnaire-Based Psychological Survey Methods on the Evaluation Results in a Patient Cohort].

Objective To assess the influences of self-and interviewer-administered methods on the scores of anxiety and depression questionnaires among the patients with sports injuries.Methods A total of 532 participants with sports injuries treated in the Sports Medicine Center of West China Hospital,Sichuan University from November 2022 to May 2023 were included.They were randomly assigned to either the interviewer-administered group (n=270) or the self-administered group (n=262) to complete the generalized anxiety disorder (GAD-7) and the patient health questionnaire (PHQ-9) scales.The total scores and prevalence rates of anxiety and depression were compared between the two groups.Results There was no statistically significant difference in gender,occupation,or surgical site between the two groups (all P>0.05).The self-administered group had higher scores of GAD-7 and PHQ-9 scales than the interviewer-administered group (P<0.001,P<0.001).A greater proportion of participants in the self-administered group than in the interview-administered group met the criteria for mild to moderate anxiety and depression (P<0.001,P=0.002).The prevalence rates of moderate to severe anxiety (GAD-7≥10) and depression (PHQ-9≥10) showed no statistically significant difference between the two groups (P=0.761,P=0.086).Conclusion This study demonstrates that the participants in the self-administered group are more likely to report mild to moderate symptoms of anxiety and depression than those in the interviewer-administered group.

Design of Proteolytic-Resistant Antifungal Peptides by Utilizing Minimum d-Amino Acid Ratios.

Antifungal peptides are an appealing alternative to standard antifungal medicines due to their unique mechanism of action and low-level resistance. However, their susceptibility to protease degradation keeps hindering their future development. Herein, a library was established to design peptides with protease resistance and high antifungal activity. The peptides were incorporated with minimal D-amino acids to further improve the protease stability. The most active peptide, IR3, demonstrated good antifungal activity and low toxicity, and its molecular integrity was maintained after protease hydrolysis for 8 h at 2 mg/mL. Furthermore, IR3 could permeate the fungal cell wall, disrupt the cell membrane, produce reactive oxygen species, and induce apoptosis in fungal cells. In vivo experiments confirmed that IR3 could effectively treat fungal keratitis. Collectively, these findings suggest that IR3 is a promising antifungal agent and may be beneficial in the design and development of protease-resistant antifungal peptides.

Cobalt-Catalyzed Borylative Reduction of Azobenzenes to Hydrazobenzenes via a Diborylated-Hydrazine Intermediate.

Cobalt-catalyzed borylative reduction of azobenzenes using pinacolborane is developed. The simple cobalt chloride catalyst and reaction conditions make this protocol attractive for hydrazobenzene synthesis. This borylative reduction shows good functional group compatibility and can be readily scaled up to the gram scale. Preliminary mechanistic studies clarified the proton source of the hydrazine products. This cobalt-catalyzed azobenzene borylative reaction provides a practical protocol to prepare synthetically useful diborylated hydrazines.

Industrial effluents and N-nitrosamines in karst aquatic systems: a study on distribution and ecological implications.

The discharge of electroplating wastewater, containing high concentrations of N-nitrosamines, poses significant risks to human health and aquatic ecosystems. Karst aquatic environment is easily impacted by N-nitrosamines due to the fragile surface ecosystem. However, it's still unclear in understanding N-nitrosamine transformation in karst water systems. To explore the response and transport of nine N-nitrosamines in electroplating effluent within both karst surface water and groundwater, different river and groundwater samples were collected from both the upper and lower reaches of the effluent discharge areas in a typical karst industrial catchment in Southwest China. Results showed that the total average concentrations of N-nitrosamines (∑NAs) in electroplating effluent (1800 ng/L) was significantly higher than that in the receiving river water (130 ng/L) and groundwater (70 ng/L). The dynamic nature of karst aquifers resulted in comparable average concentrations of ∑NAs in groundwater (70 ng/L) and river water (79 ng/L) at this catchment. Based on the principal component analysis and multiple linear regression analysis, the electroplating effluent contributed 89% and 53% of N-nitrosamines to the river water and groundwater, respectively. The results based on the species sensitivity distribution model revealed N-nitrosodibutylamine as a particularly toxic compound to aquatic organisms. Furthermore, the average N-nitrosamine carcinogenic risk was significantly higher in lower groundwater reaches compared to upper reaches. This study represents a pioneering effort in considering specific N-nitrosamine properties in evaluating their toxicity and constructing species sensitivity curves. It underscores the significance of electroplating effluent as a primary N-nitrosamine source in aquatic environments, emphasizing their swift dissemination and significant accumulation in karst groundwater.

ATP2C1 knockdown induces abnormal expressions of cytoskeletal and tight junction proteins mimicking Hailey-Hailey disease.

Background Hailey-Hailey disease (HHD) is a rare, autosomal dominant, hereditary skin disorder characterised by epidermal acantholysis. The HHD-associated gene ATPase calcium-transporting type 2C member 1 (ATP2C1) encodes the protein secretory pathway Ca2+ ATPase1 (SPCA1), playing a critical role in HHD pathogenesis. Aims We aimed to investigate the effect of ATP2C1 knockdown on keratinocytes that mimicked acantholysis in HHD. Methods Immunohistochemistry (IHC) was employed to evaluate the levels of cytoskeletal and tight junction proteins such as SPCA1, P-cofilin, F-actin, claudins, occludin, and zonula occludens 1 in the skin biopsies of patients with HHD. Subsequently, the expression of these proteins in cultured ATP2C1 knockdown keratinocytes was analysed using Western blotting and immunofluorescence. Furthermore, we assessed the proliferation, apoptosis, and intracellular Ca2+ concentrations in the ATP2C1-knocked keratinocytes. Results The results showed decreased levels of these proteins (SPCA1, P-cofilin, F-actin, claudins, occluding, and zonula occludens 1) in HHD skin lesions. Moreover, their levels decreased in human keratinocytes transfected with ATP2C1 short hairpin RNA, accompanied by morphological acantholysis. Furthermore, the proliferation and apoptosis of the keratinocytes, as well as intracellular calcium concentrations in these cells, were not affected. Limitations The limitations of this study are the absence of animal experiments and the failure to explore the relationship between skeletal and tight junction proteins. Conclusion The present study indicated that ATP2C1 inhibition led to abnormal levels of the cytoskeletal and tight junction proteins in the keratinocytes. Therefore, keratinocytes can mimic HHD-like acantholysis and serve as an in vitro model, helping develop treatment strategies against HHD.

Magnetotactic Bacteria AMB-1 with Active Deep Tumor Penetrability for NIR-II Photothermal Tumor Therapy.

The complex tumor structure and microenvironment such as abnormal tumor vasculature, dense tumor matrix, and elevated interstitial fluid pressure greatly hinder the penetration and retention of therapeutic agents in solid tumors. The development of an advanced method for robust penetration and retention of therapeutic agents in tumors is of great significance for efficient tumor treatments. In this work, we demonstrated that magnetotactic bacteria AMB-1 with hypoxic metabolism characteristics can actively penetrate the tumor to selectively colonize deep hypoxic regions, which emerge as a promising intelligent drug carrier. Furthermore, AMB-1 presents intrinsic second near-infrared (NIR-II) photothermal performance that can efficiently convert a 1064 nm laser into heat for tumor thermal ablation. We believe that our investigations not only develop a novel bacteria-based photothermal agent but also provide useful insights for the development of advanced tumor microbial therapies.

Single-cell transcriptome analysis reveals heterogeneity of neutrophils in non-small cell lung cancer.

BACKGROUND: Lung cancer stands out as a highly perilous malignant tumor with severe implications for human health. There has been a growing interest in neutrophils as a result of their role in promoting cancer in recent years. Thus, the present study aimed to investigate the heterogeneity of neutrophils in non-small cell lung cancer (NSCLC). METHODS: Single-cell RNA sequencing of tumor-associated neutrophils (TANs) and polymorphonuclear neutrophils sourced from the Gene Expression Omnibus database was analyzed. Moreover, cell-cell communication, differentiation trajectories and transcription factor analyses were performed. RESULTS: Neutrophils were found to be closely associated with macrophages. Four major types of TANs were identified: a transitional subcluster that migrated from blood to tumor microenvironment (TAN-0), an inflammatory subcluster (TAN-1), a subpopulation that displayed a distinctive transcriptional signature (TAN-2) and a final differentiation state that promoted tumor formation (TAN-3). Meanwhile, TAN-3 displayed a marked increase in glycolytic activity. Finally, transcription factors were analyzed to uncover distinct TAN cluster-specific regulons. CONCLUSIONS: The discovery of the dynamic characteristics of TANs in the present study is anticipated to contribute to yielding a better understanding of the tumor microenvironment and advancing the treatment of NSCLC.

Association of pre-existing depression and anxiety with Omicron variant infection.

Pre-existing psychiatric disorders were linked to an increased susceptibility to COVID-19 during the initial outbreak of the pandemic, while evidence during Omicron prevalence is lacking. Leveraging data from two prospective cohorts in China, we identified incident Omicron infections between January 2023 and April 2023. Participants with a self-reported history or self-rated symptoms of depression or anxiety before the Omicron pandemic were considered the exposed group, whereas the others were considered unexposed. We employed multivariate logistic regression models to examine the association of pre-existing depression or anxiety with the risk of any or severe Omicron infection indexed by medical interventions or severe symptoms. Further, we stratified the analyses by polygenic risk scores (PRSs) for COVID-19 and repeated the analyses using the UK Biobank data. We included 10,802 individuals from the Chinese cohorts (mean age = 51.1 years, 45.6% male), among whom 7841 (72.6%) were identified as cases of Omicron infection. No association was found between any pre-existing depression or anxiety and the overall risk of Omicron infection (odds ratio [OR] =1.04, 95% confidence interval [CI] 0.95-1.14). However, positive associations were noted for severe Omicron infection, either as infections requiring medical interventions (1.26, 1.02-1.54) or with severe symptoms (≥3: 1.73, 1.51-1.97). We obtained comparable estimates when stratified by COVID-19 PRS level. Additionally, using clustering method, we identified eight distinct symptom patterns and found associations between pre-existing depression or anxiety and the patterns characterized by multiple or complex severe symptoms including cough and taste and smell decline (ORs = 1.42-2.35). The results of the UK Biobank analyses corroborated findings of the Chinese cohorts. In conclusion, pre-existing depression and anxiety was not associated with the risk of Omicron infection overall but an elevated risk of severe Omicron infection, supporting the continued efforts on monitoring and possible early intervention in this high-risk population during Omicron prevalence.

Effects of subtle variation in forest canopy openness on cache pilferage and its implications for forest regeneration.

Scatter-hoarding rodents play important roles in plant regeneration and species coexistence in many forest ecosystems. Cache pilferage, the behavior of rodents seeking or relocating seeds cached by other individuals, is ubiquitous during the scatter-hoarding process. The effects of canopy openness on cache pilferage have received considerable attention, most of which have focused on the comparison between full canopy cover and completely open areas, such as forest gaps. However, little attention has been given to whether the subtle variation in forest canopy openness affects cache pilferage, although subtle variation in light environments exists in many forests, especially tropical and subtropical forests, where the overall canopy is large and the forest window is relatively small. Here, we directly tested these questions by simulating 400 artificial caches, each containing one seed from four selected tree species, in a subtropical forest in southwestern China. The overall canopy openness of the forest was relatively small (with a mean value of 11.1%), but subtle spatial variation still existed (ranging from 5.7% to 19.5%). Overall, caches with lower canopy openness were more likely to be pilfered and removed faster, although not all species showed the same pattern. Our study highlights that subtle variation in forest canopy openness, even in a closed primary forest, has significant effects on cache pilferage by rodents, which may influence the following seed germination and forest regeneration processes. Additionally, seedling species composition may further be altered because the canopy effects on cache pilferage are species-specific.