The Role of JAK-STAT-SOCS1 Axis in Tumorigenesis, Malignant Progression and Lymphatic Metastasis of Penile Cancer.

Background: To uncover the potential significance of JAK-STAT-SOCS1 axis in penile cancer, our study was the pioneer in exploring the altered expression processes of JAK-STAT-SOCS1 axis in tumorigenesis, malignant progression and lymphatic metastasis of penile cancer. Methods: In current study, the comprehensive analysis of JAK-STAT-SOCS1 axis in penile cancer was analyzed via multiple analysis approaches based on GSE196978 data, single-cell data (6 cancer samples) and bulk RNA data (7 cancer samples and 7 metastasis lymph nodes). Results: Our study observed an altered molecular expression of JAK-STAT-SOCS1 axis during three different stages of penile cancer, from tumorigenesis to malignant progression to lymphatic metastasis. STAT4 was an important dominant molecule in penile cancer, which mediated the immunosuppressive tumor microenvironment by driving the apoptosis of cytotoxic T cell and was also a valuable biomarker of immune checkpoint inhibitor treatment response. Conclusions: Our findings revealed that the complexity of JAK-STAT-SOCS1 axis and the predominant role of STAT4 in penile cancer, which can mediate tumorigenesis, malignant progression, and lymphatic metastasis. This insight provided valuable information for developing precise treatment strategies for patients with penile cancer.

Autophagy activated by GR/miR-421-3p/mTOR pathway as a compensatory mechanism participates in chondrodysplasia induced by prenatal caffeine exposure in male fetal rats.

Autophagy has been implicated in the developmental toxicity of multiple organs in offspring caused by adverse environmental conditions during pregnancy. We have previously found that prenatal caffeine exposure (PCE) can cause fetal overexposure to maternal glucocorticoids, leading to chondrodysplasia. However, whether autophagy is involved and what role it plays has not been reported. In this study, a PCE rat model was established by gavage of caffeine (120mg/kg.d) on gestational day 9-20. The results showed that reduced cartilage matrix synthesis in male fetal rats in the PCE group was accompanied by increased autophagy compared to the control group. Furthermore, the expression of mTOR, miR-421-3p, and glucocorticoid receptor (GR) in male fetal rat cartilage of PCE group was increased. At the cellular level, we confirmed that corticosterone inhibited matrix synthesis in fetal chondrocytes while increasing autophagic flux. However, administration of autophagy enhancer (rapamycin) or inhibitor (bafilomycin A1 or 3-methyladenine) partially increased or further decreased aggrecan expression respectively. At the same time, we found that corticosterone could increase the expression of miR-421-3p through GR and target to inhibit the expression of mTOR, thereby enhancing autophagy. In conclusion, PCE can cause chondrodysplasia and autophagy enhancement in male fetal rats. Intrauterine high corticosterone activates GR/miR-421-3p signaling and down-regulates mTOR signaling in fetal chondrocytes, resulting in enhanced autophagy, which can partially compensate for corticosterone-induced fetal chondrodysplasia. This study confirmed the compensatory protective effect of autophagy on the developmental toxicity of fetal cartilage induced by PCE and its epigenetic mechanism, providing novel insights for exploring the early intervention and therapeutic target of fetal-originated osteoarthritis.

Symmetry-Reduction Enhanced Polarization-Sensitive Photoresponse Based on One-Dimensional van der Waals Materials.

Designing high-performance polarization-sensitive photodetectors is essential for photonic device applications. Anisotropic one-dimensional (1D) van der Waals (vdW) materials have provided a promising platform to that end. Despite significant advances in 1D vdW photonic devices, their performance is still far from delivering practical potential. Herein, we propose the design of high-performance polarization-sensitive photodetectors using unique 1D vdW materials. By leveraging the chemical vapor transport technique, we successfully fabricate high-quality 1D vdW Nb2Pd1-xSe5 (x = 0.29) nanowires. The 1D vdW Nb2Pd1-xSe5 photodetector exhibits a high mobility of ∼56 cm2/(V s) and superior photoresponse performance, including a high responsivity of 1A/W and an ultrafast response time of ∼8 µs under 638 nm illumination. Moreover, the 1D vdW Nb2Pd1-xSe5 photodetector demonstrates excellent polarization-sensitive photoresponse with a degree of linear polarization (DOLP) up to 0.85 and can be modulated by adjusting the gate voltage, laser power density, and wavelength. Those exceptional performance are believed to be relevant to the symmetry-reduction induced by the partial occupation of Pd sites. This study offers feasible approaches to enhance the anisotropy of 1D vdW materials and the modulation of their polarization-sensitive photoresponse, which may provide deep insights into the physical origin of anisotropic properties of 1D vdW materials.

Copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to testicular damage and impaired spermatogenesis in Wilson disease.

Copper is a toxic heavy metal that causes various damage when it accumulates in the body beyond the physiological threshold. Wilson disease (WD) is an inherited disorder characterized by impaired copper metabolism. Reproductive damage in male patients with WD is gradually attracting attention. However, the underlying mechanisms of copper toxicity are unclear. In this study, we investigated the role of inflammation and PANoptosis in testicular damage and impaired spermatogenesis caused by copper deposition using the WD model toxic milk (TX) mice. Copper chelator-penicillamine and toll-like receptor 4 (TLR4) inhibitor-eritoran were used to intervene in TX mice in our animal experiment methods. Testis samples were collected from mice for further analysis. The results showed that the morphology and ultrastructure of the testis and epididymis in TX mice were damaged, and the sperm counts decreased significantly. The TLR4/nuclear factor kappa-B (NF-κB) signaling pathway was activated by copper deposition, which led to the upregulation of serum and testicular inflammatory factors in TX mice. Meanwhile, pyroptosis, apoptosis, and necroptosis were significant in the testis of TX mice. Both chelated copper or inhibited TLR4 expression markedly suppressed the TLR4/NF-κB signaling pathway, thereby reducing the expression of inflammatory factors. PANoptosis in the testis of TX mice was also reversed. Our study indicated that pathological copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to toxic testicular damage and impaired spermatogenesis in WD.

Plant Growth-Promoting Bacteria Influence Microbial Community Composition and Metabolic Function to Enhance the Efficiency of Hybrid pennisetum Remediation in Cadmium-Contaminated Soil.

The green and efficient remediation of soil cadmium (Cd) is an urgent task, and plant-microbial joint remediation has become a research hotspot due to its advantages. High-throughput sequencing and metabolomics have technical advantages in analyzing the microbiological mechanism of plant growth-promoting bacteria in improving phytoremediation of soil heavy metal pollution. In this experiment, a pot trial was conducted to investigate the effects of inoculating the plant growth-promoting bacterium Enterobacter sp. VY on the growth and Cd remediation efficiency of the energy plant Hybrid pennisetum. The test strain VY-1 was analyzed using high-throughput sequencing and metabolomics to assess its effects on microbial community composition and metabolic function. The results demonstrated that Enterobacter sp. VY-1 effectively mitigated Cd stress on Hybrid pennisetum, resulting in increased plant biomass, Cd accumulation, and translocation factor, thereby enhancing phytoremediation efficiency. Analysis of soil physical-chemical properties revealed that strain VY-1 could increase soil total nitrogen, total phosphorus, available phosphorus, and available potassium content. Principal coordinate analysis (PCoA) indicated that strain VY-1 significantly influenced bacterial community composition, with Proteobacteria, Firmicutes, Chloroflexi, among others, being the main differential taxa. Redundancy analysis (RDA) revealed that available phosphorus, available potassium, and pH were the primary factors affecting bacterial communities. Partial Least Squares Discriminant Analysis (PLS-DA) demonstrated that strain VY-1 modulated the metabolite profile of Hybrid pennisetum rhizosphere soil, with 27 differential metabolites showing significant differences, including 19 up-regulated and eight down-regulated expressions. These differentially expressed metabolites were primarily involved in metabolism and environmental information processing, encompassing pathways such as glutamine and glutamate metabolism, α-linolenic acid metabolism, pyrimidine metabolism, and purine metabolism. This study utilized 16S rRNA high-throughput sequencing and metabolomics technology to investigate the impact of the plant growth-promoting bacterium Enterobacter sp. VY-1 on the growth and Cd enrichment of Hybrid pennisetum, providing insights into the regulatory role of plant growth-promoting bacteria in microbial community structure and metabolic function, thereby improving the microbiological mechanisms of phytoremediation.

Modeling Nitrogen Fate and Water and Nitrogen Use Efficiencies under Different Greenhouse Vegetable Production Systems Using the WHCNS-Veg Model.

Quantitative evaluation of the effects of diverse greenhouse vegetable production systems (GVPS) on vegetable yield, soil water consumption, and nitrogen (N) fates could provide a scientific basis for identifying optimum water and fertilizer management practices for GVPS. This research was conducted from 2013 to 2015 in a greenhouse vegetable field in Quzhou County, North China. Three production systems were designed: conventional (CON), integrated (INT), and organic (ORG) systems. The WHCNS-Veg model was employed for simulating vegetable growth, water dynamics, and fates of N, as well as water and N use efficiencies (WUE and NUE) for four continuous growing seasons. The simulation results revealed that nitrate leaching and gaseous N emissions constituted the predominant N loss within GVPS, which separately accounted for 11.5-59.4% and 6.0-21.1% of the N outputs. The order of vegetable yield, N uptake, WUE, and NUE under different production systems was ORG > INT > CON, while the order of nitrate leaching and gaseous N loss was CON > INT > ORG. Compared to CON, ORG exhibited a significant increase in yield, N uptake, WUE, and NUE by 24.6%, 24.2%, 26.1%, and 89.7%, respectively, alongside notable reductions in nitrate leaching and gaseous N loss by 67.7% and 63.2%, respectively. The ORG system should be recommended to local farmers.

Distribution patterns and environmental risk assessments of microplastics in the lake waters and sediments from eight typical wetland parks in Changsha city, China.

The quality of water in urban parks is closely related to people's daily lives, but the pollution caused by microplastics in park water and sediments has not been comprehensively studied. Therefore, eight typical parks in the urban area of Changsha, China, were selected, and Raman spectroscopy was used to explore the spatial distributions and compositions of the microplastics in the water and sediments, analyze their influencing factors, and evaluate their environmental risks. The results showed that the abundances of surface water microplastics in all parks ranged from 150 to 525 n L-1, and the abundances of sediment microplastics ranged from 120 to 585 n kg-1. The microplastics in the surface water included polyethylene terephthalate (PET), chlorinated polyethylene (CPE), and fluororubber (FLU), while those in the sediments included polyvinyl chloride (PVC), wp-acrylate copolymer (ACR), and CPE. Regression analyses revealed significant positive correlations between human activities and the abundances of microplastics in the parks. Among them, the correlations of population, industrial discharge and domestic wastewater discharge with the abundance of microplastics in park water were the strongest. However, the correlations of car flow and tourists with the abundance of microplastics in park water were the weakest. Based on the potential ecological risk indices (PERI) classification assessment method, the levels of microplastics in the waters and sediments of the eight parks were all within the II-level risk zone (53-8,549), among which the risk indices for Meixi Lake and Yudai Lake were within the IV risk zone (1,365-8,549), which may have been caused by the high population density near the park. This study provides new insights into the characteristics of microplastics in urban park water and sediment.

A PROTEIN COMPLEX OF LIVER ORIGIN ACTIVATES A PRO-INFLAMMATORY PROGRAM THAT DRIVES HEPATIC AND INTESTINAL INJURY IN ALCOHOL-ASSOCIATED LIVER DISEASE.

BACKGROUND AND AIMS: There is limited information on how the liver-to-gut axis contributes to alcohol-associated liver disease (AALD). We previously identified that high-mobility group box-1 (HMGB1) undergoes oxidation in hepatocytes and demonstrated elevated serum levels of oxidized HMGB1 ([O] HMGB1) in alcoholic patients. Since interleukin-1 beta (IL1B) increases in AALD, we hypothesized hepatocyte-derived [O] HMGB1 could interact with IL1B to activate a pro-inflammatory program that, besides being detrimental to the liver, drives intestinal barrier dysfunction. RESULTS: Alcohol-fed RageΔMye mice exhibited decreased NFκB signaling, a pro-inflammatory signature, and reduced total intestinal permeability, resulting in protection from AALD. Additionally, [O] HMGB1 bound and signaled through the receptor for advanced-glycation end-products (RAGE) in myeloid cells, driving hepatic inflammation, intestinal permeability, and increased portal blood lipopolysaccharide in AALD. We identified that [O] HMGB1 formed a complex with IL1B, which was found in the livers of patients with acute alcoholic hepatitis and mice with AALD. This complex originated from the liver, as it was absent in the intestine when hepatocytes did not produce [O] HMGB1. Mechanistically, the complex bound RAGE in Kupffer cells and macrophages induces a pro-inflammatory program. Moreover, it bound RAGE in intestinal macrophages and epithelial cells, leading to intestinal inflammation, altered intestinal epithelial cell tight junction protein expression, increased intestinal permeability, and elevated portal blood lipopolysaccharide, enhancing AALD pathogenesis. CONCLUSION: We identified a protein complex of liver origin that amplifies the pro-inflammatory feedback loop in AALD; therefore, targeting this complex could have significant therapeutic potential.

SFTSV nucleoprotein mediates DNA sensor cGAS degradation to suppress cGAS-dependent antiviral responses.

Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm, leading to an antiviral interferon response. A tick-borne Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), is an RNA virus that causes a severe emerging viral hemorrhagic fever in Asia with a high case fatality rate of up to 30%. However, it is unclear whether cGAS interacts with SFTSV infection. In this study, we found that SFTSV infection upregulated cGAS RNA transcription and protein expression, indicating that cGAS is an important innate immune response against SFTSV infection. The mechanism of cGAS recognizing SFTSV is by cGAS interacting with misplaced mitochondrial DNA in the cytoplasm. Depletion of mitochondrial DNA significantly inhibited cGAS activation under SFTSV infection. Strikingly, we found that SFTSV nucleoprotein (N) induced cGAS degradation in a dose-dependent manner. Mechanically, N interacted with the 161-382 domain of cGAS and linked the cGAS to LC3. The cGAS-N-LC3 trimer was targeted to N-induced autophagy, and the cGAS was degraded in autolysosome. Taken together, our study discovered a novel antagonistic mechanism of RNA viruses, SFTSV is able to suppress the cGAS-dependent antiviral innate immune responses through N-hijacking cGAS into N-induced autophagy. Our results indicated that SFTSV N is an important virulence factor of SFTSV in mediating host antiviral immune responses. IMPORTANCE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.

Secular trends of population-attributable fractions of obesity for hypertension among US population by sex and race/ethnicity: Analysis from NHANES 1999-2018.

Obesity is a major risk factor of hypertension, therefore quantifying the contribution of obesity to hypertension is necessary. The current study aimed to investigate the changes in population-attributable fractions (PAFs) of hypertension associated with general obesity and abdominal obesity over the recent 2 decades among the US population, as well as important sub-populations. This report was performed based on national-level cross-sectional data for 46,535 adults aged 18 years and older and 20,745 children aged 8-17 from the US National Health and Nutrition Examination Survey 1999-2018. The PAFs of hypertension due to general obesity and abdominal obesity were calculated by sex, race/ethnicity, and survey year. The linear regression analysis was used to evaluate the secular trends of PAFs over the years. The prevalence of general obesity and abdominal obesity presented significantly increasing trends during the past 2 decades in the US. The PAFs of hypertension due to general obesity increased steadily from 11.9 % to 15.1 % in women with a slope of 0.38 % (95 % CI: 0.31 - 0.45 %) and from 8.4 % to 13.4 % in men with a slope of 0.46 % (95 % CI: 0.36 - 0.56 %). Similar increasing trends were also observed for the PAFs due to abdominal obesity in both women and men. Additionally, there were significantly different trends of PAFs in various races/ethnicities. Over the past 2 decades, the contributions of obesity to hypertension were gradually rising among US population, which emphasizes the importance of controlling weight to further reduce the burden of hypertension.

Effects of combined microplastic and cadmium pollution on sorghum growth, Cd accumulation, and rhizosphere microbial functions.

The interaction between microplastics (MPs) and cadmium (Cd) poses a threat to agricultural soil environments, and their effects on plant growth and rhizosphere microbial community functions are not yet clear. In this study, energy sorghum was used as a test plant to investigate the effects of two types of MPs, polystyrene (PS) and polyethylene (PE), at different particle sizes (13 µm, 550 µm) and concentrations (0.1%, 1% w/w), and Cd, as well as their interactions, on the growth of sorghum in a soil-cultivation pot experiment. The results showed that the combined effects of MP and Cd pollution on the dry weight and Cd accumulation rate in sorghum varied depending on the type, concentration, and particle size of the MPs, with an overall trend of increasing stress from combined pollution with increasing Cd content and accumulation. High-throughput sequencing analysis revealed that combined MP and Cd pollution increased bacterial diversity, and the most significant increase was observed in the abundance-based coverage estimator (ACE), Shannon, and Sobs indices in the 13 µm 1% PS+Cd treatment group. Metagenomic analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed that 19 groups of metabolic pathways, including microbial metabolism and methane metabolism, differed significantly under combined MP and Cd pollution. Hierarchical clustering results indicated that Cd treatment and combined MP and Cd treatment affected the abundances of sorghum rhizosphere soil nitrogen (N) and phosphorus (P) cycling genes and that the type of MP present was an important factor affecting N and P cycling genes. The results of this study provide a basis for exploring the toxic effects of combined MP and Cd pollution and for conducting soil environmental risk assessments.

Ginsenoside Rb1 ameliorates lipotoxicity-induced myocardial injury in diabetes mellitus by regulating Mfn2.

PURPOSE: Diabetic cardiomyopathy is a prevalent cardiovascular complication of diabetes mellitus. This study aimed to investigate the effects of ginsenoside Rb1 (GRb1) on the diabetic myocardium. METHODS: Leptin receptor-deficient db/db mice and palmitic acid (PA)-treated cardiomyocyte models were utilized. Cardiac systolic and diastolic function, mitochondrial morphology, and respiratory chain function were determined. The expression of mitochondrial dynamics proteins was measured. Mitofusin 2 (Mfn2) overexpression and inhibition were achieved by lentiviral infection and small interfering RNA (siRNA) transfection. RESULTS: In comparison to non-diabetic mice, db/db mice exhibited significant increases in body weight, blood glucose, blood lipids, and cardiac free fatty acid levels. This was accompanied by myocardial hypertrophy and left ventricular diastolic dysfunction, which were significantly ameliorated by GRb1 intervention. Stimulation with PA increased oxidative stress and apoptosis, and decreased viability in H9c2 cardiomyocytes. PA also reduced sarcomere contractility and relaxation in adult mice ventricular myocytes. PA-induced cellular and mitochondrial damage were reversed with GRb1 treatment. The cardiac tissue of db/db mice and PA-treated cardiomyocytes exhibited a decrease in Mfn2 expression, which was markedly improved by GRb1. Mfn2 overexpression reversed PA-induced mitochondrial fragmentation and functional damage in cardiomyocytes, while inhibition of Mfn2 expression by siRNA transfection blocked the protective effects of GRb1. CONCLUSION: GRb1 alleviated myocardial lipid accumulation and mitochondrial injury, and attenuated ventricular diastolic dysfunction in diabetic mice. The regulation of Mfn2 was involved in the protective effects of GRb1 against lipotoxic myocardial injury.

A Pyroglutamate Aminopeptidase 1 Responsive Fluorescence Imaging Probe for Real-Time Rapid Differentiation between Thyroiditis and Thyroid Cancer.

Current diagnostic methods for thyroid diseases, including blood tests, ultrasound, and biopsy, always have difficulty diagnosing thyroiditis accurately, occasionally mistaking it for thyroid cancer. To address this clinical challenge, we developed Ox-PGP1, a novel fluorescent probe realizing rapid, noninvasive, and real-time diagnostic techniques. This is the first imaging tool capable of noninvasively distinguishing between thyroiditis and thyroid cancer. Ox-PGP1 was introduced as a fluorescent probe custom-built for the specific detection and quantification of pyroglutamate aminopeptidase 1 (PGP-1), a known pivotal biomarker of inflammation. Ox-PGP1 overcame the disadvantages of traditional enzyme-responsive fluorescent probes that relied on the intramolecular charge transfer (ICT) mechanism, including the issue of high background fluorescence, while offering exceptional photostability under laser irradiation. The spectral properties of Ox-PGP1 were meticulously optimized to enhance its biocompatibility. Furthermore, the low limit of detection (LOD) of Ox-PGP1 was determined to be 0.09 µg/mL, which demonstrated its remarkable sensitivity and precision. Both cellular and in vivo experiments validated the capacity of Ox-PGP1 for accurate differentiation between normal, inflammatory, and cancerous thyroid cells. Furthermore, Ox-PGP1 showed the potential to rapidly and sensitively differentiate between autoimmune thyroiditis and anaplastic thyroid carcinoma in a mouse model, achieving results in just 5 min. The successful design and application of Ox-PGP1 represent a substantial advancement in technology over traditional diagnostic approaches, potentially enabling earlier interventions for thyroid diseases.

Evaluation of the Effectiveness of "5E" Comprehensive Injury Prevention Strategy for Fall Prevention Among the Rural Elderly - Six Pilot Villages, Yunnan Province and Chongqing Municipality, China, 2018-2023.

What is already known about this topic?: The mortality rate and disease burden associated with falls among the elderly in China are on the rise. Interventions can play a crucial role in preventing and managing falls. What is added by this report?: The application of the "5E" injury prevention strategy led to a decrease in both the occurrence of falls and the likelihood of subsequent falls. Regular physical activity and maintaining a positive outlook were identified as protective measures against falls, while sleep issues and hearing impairment were found to increase the risk of falling. What are the implications for public health practice?: The group-based comprehensive intervention strategy is crucial as it offers an innovative intervention model and empirical evidence for decreasing fall rates among elderly individuals living in rural areas.

Clinical outcomes of coronavirus disease in patients with breast cancer treated with granulocyte colony-stimulating factor following chemotherapy: Triangulation of evidence using population-based cohort and Mendelian randomization analyses.

Recombinant human granulocyte colony-stimulating factor (G-CSF) administration in patients with cancer and coronavirus disease (COVID-19) remains controversial. Concerns exist that it may worsen COVID-19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy-induced neutropenia (CIN) or febrile neutropenia post-chemotherapy. Here, we determined whether prophylactic or therapeutic G-CSF administration following chemotherapy exacerbates COVID-19 progression to severe/critical conditions in breast cancer patients with COVID-19. Between December 2022 and February 2023, all 503 enrolled breast cancer patients had concurrent COVID-19 and received G-CSF post-chemotherapy, with most being vaccinated pre-chemotherapy. We prospectively observed COVID-19-related adverse outcomes, conducted association analyses, and subsequently performed Mendelian randomization (MR) analyses to validate the causal effect of genetically predicted G-CSF or its associated granulocyte traits on COVID-19 adverse outcomes. Only 0.99% (5/503) of breast cancer patients experienced COVID-19-related hospitalization following prophylactic or therapeutic G-CSF administration after chemotherapy. No mortality or progression to severe/critical COVID-19 occurred after G-CSF administration. Notably, no significant associations were observed between the application, dosage, or response to G-CSF and COVID-19-related hospitalization (all p >.05). Similarly, the MR analyses showed no evidence of causality of genetically predicted G-CSF or related granulocyte traits on COVID-19-related hospitalization or COVID-19 severity (all p >.05). There is insufficient evidence to substantiate the notion that the prophylactic or therapeutic administration of G-CSF after chemotherapy for managing CIN in patients with breast cancer and COVID-19 would worsen COVID-19 outcomes, leading to severe or critical conditions, or even death, especially considering the context of COVID-19 vaccination.

CD276-dependent efferocytosis by tumor-associated macrophages promotes immune evasion in bladder cancer.

Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may turn immune suppressive, and tumor associated macrophages are playing a role in this transition. Here, we show that CD276, expressed on tumor-associated macrophages (TAM), play a role in diminishing the immune response against tumors. Using a model of tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in BLCA male mice we show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcription factor JUN to regulate the expression of AXL and MerTK, resulting in enhanced efferocytosis in TAMs. Proving the principle, we show that simultaneous blockade of CD276 and PD-1 restrain tumor growth better than any of the components as a single intervention. Taken together, our study supports a role for CD276 in efferocytosis by TAMs, which is potentially targetable for combination immune therapy.

RNA modification-related genes illuminate prognostic signature and mechanism in esophageal squamous cell carcinoma.

Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m5C modifications selectively enhance the translation efficiency of CDH1 mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6's function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.

Pd NP-loaded covalent organic framework for pH-switched Pickering emulsion catalytic dechlorination.

Quinoline carboxylic acid-linked and Pd nanoparticle (NP)-loaded COF nanospheres were constructed via a three-component one-pot Doebner reaction and post-synthetic metalation. The obtained Pd@DhaTAPB-COOH solid stabilizer can greatly promote the pH-switched recyclable Pickering interfacial dechlorination reaction, which sheds light on the bright future of smart Pickering emulsion catalysis.

A pan-cancer multi-omics analysis of lactylation genes associated with tumor microenvironment and cancer development.

Background: Lactylation is a significant post-translational modification bridging the gap between cancer epigenetics and metabolic reprogramming. However, the association between lactylation and prognosis, tumor microenvironment (TME), and response to drug therapy in various cancers remains unclear. Methods: First, the expression, prognostic value, and genetic and epigenetic alterations of lactylation genes were systematically explored in a pan-cancer manner. Lactylation scores were derived for each tumor using the single-sample gene set enrichment analysis (ssGSEA) algorithm. The correlation of lactylation scores with clinical features, prognosis, and TME was assessed by integrating multiple computational methods. In addition, GSE135222 data was used to assess the efficacy of lactylation scores in predicting immunotherapy outcomes. The expression of lactylation genes in breast cancers and gliomas were verified by RNA-sequencing. Results: Lactylation genes were significantly upregulated in most cancer types. CREBBP and EP300 exhibited high mutation rates in pan-cancer analysis. The prognostic impact of the lactylation score varied by tumor type, and lactylation score was a protective factor for KIRC, ACC, READ, LGG, and UVM, and a risk factor for CHOL, DLBC, LAML, and OV. In addition, a high lactylation score was associated with cold TME. The infiltration levels of CD8+ T, γδT, natural killer T cell (NKT), and NK cells were lower in tumors with higher lactylation scores. Finally, immunotherapy efficacy was worse in patients with high lactylation scores than other types. Conclusion: Lactylation genes are involved in malignancy formation. Lactylation score serves as a promising biomarker for predicting patient prognosis and immunotherapy efficacy.

[Characterization of Metal Elements in Atmospheric PM2.5 and Health Risk Assessment in Heze in Winter from 2017 to 2018].

Atmospheric PM2.5 samples were collected in Heze, Shandong Province, from a total of three sampling sites at Heze College, Huarun Pharmacy, and a wastewater treatment plant between October 15, 2017 and January 31, 2018, to determine the concentrations of 21 metal elements in PM2.5 using inductively coupled plasma mass spectrometry (ICP-MS). The degree of elemental enrichment was also discussed, the health risks and potential heavy metal ecological risks were assessed. The results showed that ρ (PM2.5) ranged from 26.7 to 284.1 µg·m-3 at the three sampling sites during the sampling period, and the concentration values did not differ significantly, all of which were at high pollution levels. The highest concentrations of K were found in the three sampling sites, accounting for 31.03%, 39.47%, and 38.43% of the total, respectively, mainly due to the high contribution of biomass burning in autumn and winter in Heze, a large agricultural city. The highest concentrations of Zn, 89.70, 84.21, and 67.68 ng·m-3, were found in the trace elements at the three sampling sites, respectively. The enrichment factor results showed that the enrichment factor values of Zn, Pb, Sn, Sb, Cd, and Se were higher than 100, among which the enrichment factors of Cd and Se were higher than 2 000 and 4 000, respectively, which were significantly influenced by anthropogenic activities and might have been related to industrial production, metal smelting, road sources, and coal combustion emissions. The health risk results showed that there was some potential non-carcinogenic risk (HQ>0.1 for children and adults) for As and a combined potential non-carcinogenic risk (HI>0.1) and some potential carcinogenic risk (CRT>1×10-6) for both children and adults at the three sampling sites. There was a more significant carcinogenic risk (CRT>1×10-4) for adults at the wastewater treatment plant, and the slightly higher carcinogenic risk for adults than that for children may have been related to the longer outdoor activity and higher PM2.5 exposure for adults. The elements with the highest potential ecological risk values were Cd, As, and Pb, with Cd exhibiting a very high potential ecological risk that should be taken seriously. All three sampling sites showed a very high combined potential ecological risk, with the intensity spatially expressed as Heze College>Huarun Pharmacy>wastewater treatment plant.