eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Dissecting prostate Cancer: Single-Cell insight into Macrophage Diversity, molecular Prognosticators, and the role of Peptidylprolyl Isomerase F.

BACKGROUND: Prostate cancer remains a prominent challenge in oncology, with advanced stages showing poor prognosis. The tumor microenvironment (TME), and particularly tumor-associated macrophages (TAMs), plays a crucial role in disease progression. This study explores the single-cell transcriptomics of prostate cancer, determines macrophage heterogeneity, identifies prognostic gene markers, and assesses the role of PPIF in TAMs. METHODS: Single-cell RNA sequencing data from the GEO database (GSE176031) and transcriptome data from the TCGA were processed to characterize cell populations and identify prognostic genes in prostate cancer. Macrophage subpopulations were examined through clustering, followed by gene set scoring based on migration, activation, and proliferation. PPIF expression in macrophages was investigated using multiplex immunofluorescence staining on matched prostate cancer and adjacent non-tumoral tissues. RESULTS: The single-cell analysis identified 9,178 cells, categorized into 10 principal cell types, with macrophages constituting a significant part of the immune microenvironment. Four macrophage subgroups demonstrated distinct functional pathways: phagocytic, immune-regulatory, and proliferative. A total of 39 genes correlated with prostate cancer prognosis were identified, of which 10 carried the most significant prognostic information. Peptidylprolyl Isomerase F (PPIF) expression was significantly higher in TAMs from tumor tissue than normal tissue, indicating its potential regulatory role in the immune microenvironment. CONCLUSION: The intricate cellular architecture of the prostate cancer TME has been elucidated, with a focus on macrophage heterogeneity and functional specialization. Prognostic genes, including PPIF, were associated with survival outcomes, providing potential therapeutic targets. PPIF's prominent expression in TAMs may serve as a lever in cancer progression, warranting further investigation as a biomarker and a molecule of interest for therapeutic targeting within the prostate cancer milieu.

Synergistic effect between S and Te enhancing the electrochemical behavior of heteroatomic TeS-x cathodes in aqueous Zn-TeS batteries.

Aqueous Zn-S batteries (AZSBs) have garnered increasing attention in the energy storage field owing to their high capacity, energy density, and cost effectiveness. Nevertheless, sulfur (S) cathodes face challenges, primarily stemming from sluggish reaction kinetics and the formation of an irreversible byproduct (SO42-) during the charge, hindering the progress of AZSBs. Herein, Te-S bonds within S-based cathodes were introduced to enhance electron and ion transport and facilitate the conversion reaction from zinc sulfide (ZnS) to S. This was achieved by constructing heteroatomic TeS-x@Ketjen black composite cathodes (HM-TeS-x@KB, where x  = 36, 9, and 4). The HM-TeS-9@KB electrode exhibits long-term cycling stability, maintaining a capacity decay rate of 0.1 % per cycle over 450 cycles at a current density of 10 A g-1. Crucially, through a combination of experimental data analysis and theoretical calculations, the impact mechanism of Te on the charge and discharge of S active materials within the HM-TeS-9@KB cathode in AZSBs was investigated. The presence of Te-S bonds boost the intrinsic conductivity and wettability of the HM-TeS-9@KB cathode. Furthermore, during the charge, the interaction of preferentially oxidized Te with S atoms within ZnS promotes the oxidation reaction from ZnS to S and suppresses the irreversible side reaction between ZnS and H2O. These findings indicate that the heteroatomization of chalcogen S molecules represents a promising approach for enhancing the electrochemical performance of S cathodes in AZSBs.

Changes in seminal plasma microecological dynamics and the mechanistic impact of core metabolite hexadecanamide in asthenozoospermia patients.

Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large-scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi-omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS-I), moderate AZS (AZS-II), and severe AZS (AZS-III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS-I) and an AZS group (AZS-II and AZS-III). Correlation and cross-reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium-Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite-targeting gene analysis and single-cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.

Investigation of pollutants accumulation in the submerged zone for pyrite-based bioretention facilities under continuous rainfall events.

Submerged zone in bioretention facilities for stormwater treatment has been approved to be an effective structure amendment to improve denitrification capability. However, the role and influence of water quality changes in the submerged zone under natural continuous random rainfall patterns are still not clear, especially when the rainfall is less than the pore water in the submerged zone. In this study, continuous rainfall events with different rainfall volume (light rain-light rain-heavy rain) were designed in a lab-scale woodchip mulched pyrite bioretention facility to test the effects of rainfall pattern. The results exhibited that light rain events significantly affected the pollutant removal performance of bioretention for the next rainfall. Different effects were observed during the long-term operation. In the 5th month, light rain reduced the ammonia removal efficiency of subsequent rainstorm events by 8.70%, while in the 12th month, when nitrate leakage occurred, light rain led to a 40.24% reduction in the next heavy rain event's nitrate removal efficiency. Additionally, light rain would also affect the concentration of by-products in the next rainfall. Following a light rain, the concentration of sulfate in the subsequent light rainfall can increase by 24.4 mg/L, and by 11.92 mg/L in a heavy rain. The water quality in the submerged zone and media characteristics analysis suggested that nitrogen conversion capacity of the substrate and microbes, such as Nitrospira (2.86%) and Thiobacillus (35.71%), as well as the in-situ accumulation of pollutants under light rain played important roles. This study clarifies the relationship between successive rainfall events and provides a more comprehensive understanding of bioretention facilities. This is beneficial for field study of bioretention facilities in the face of complex rainfall events.

Transforming crystal structures of cobalt molybdate to generate electron-rich sites for electrochemical detection of Pb(II).

BACKGROUND: Most of the investigations on distinct crystal structures of catalysts are individually focused on the difference of surface functional groups or adsorption properties, but rarely explore the changes of active sites to affect the electrocatalytic performance. Catalysts with diverse crystal structures had been applied to modified electrodes in different electrocatalytic reactions. However, there is currently a lack of an essential understanding for the role of real active sites in catalysts with crystalline structures in electroanalysis, which is crucial for designing highly sensitive sensing interfaces. RESULTS: Herein, cobalt molybdate with divergent crystal structures (α-CoMoO4 and ß-CoMoO4) were synthesized by adjusting the calcination temperature, indicating that α-CoMoO4 (800 °C) (60.00 µA µM-1) had the highest catalytic ability than ß-CoMoO4 (700 °C) (38.68 µA µM-1) and α-CoMoO4 (900 °C) (29.55 µA µM-1) for the catalysis of Pb(II). It was proved that the proportion of Co(II) and Mo(IV) as electron-rich sites in α-CoMoO4 (800 °C) were higher than ß-CoMoO4 (700 °C) and α-CoMoO4 (900 °C), possessing more electrons to participate in the valence cycles of Co(II)/Co(III) and Mo(IV)/Mo(VI) to boost the catalytic reduction of Pb(II). Specifically, Co(II) transferred a part of electrons to Mo(VI), promoting the formation of Mo(IV). Co(II) and Mo(IV), as the electron-rich sites, providing electrons to Pb(II), further accelerating the conversion of Pb(II) into Pb(0). SIGNIFICANCE: In the process of detecting Pb(II), the CoMoO4 structures under different temperatures have distinct content of electron-rich sites Co(II) and Mo(IV). α-CoMoO4 (800 °C), with the highest content are benefited to detect Pb(II). This work is conducive to understanding the effect of the changes of active sites resulting from crystal transformation on the electrocatalytic performance, and provides a way to construct sensitive electrochemical interfaces of distinct active sites.

Analysis of tumor microenvironment alterations in partially responsive rectal cancer patients treated with neoadjuvant chemoradiotherapy.

PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.

Role of the gut-muscle axis in mitochondrial function of ageing muscle under different exercise modes.

The fundamental role of the gut microbiota through the gut-muscle axis in skeletal muscle ageing is increasingly recognised. Metabolites derived from the intestinal microbiota are essential in maintaining skeletal muscle function and metabolism. The energy produced by mitochondria and moderate levels of reactive oxygen species can contribute to this process. Metabolites can effectively target the mitochondria, slowing the progression of muscle ageing and potentially representing a marker of ageing-related skeletal muscle loss. Moreover, mitochondria can contribute to the immune response, gut microbiota biodiversity, and maintenance of the intestinal barrier function. However, the causal relationship between mitochondrial function and gut microbiota crosstalk remains poorly understood. In addition to elucidating the regulatory pathways of the gut-muscle axis during the ageing process, we focused on the potential role of the "exercise-gut-muscle axis", which represents a pathway under stimulation from different exercise modes to induce mitochondrial adaptations, skeletal muscle metabolism and maintain intestinal barrier function and biodiversity stability. Meanwhile, different exercise modes can induce mitochondrial adaptations and skeletal muscle metabolism and maintain intestinal barrier function and biodiversity. Resistance exercise may promote mitochondrial adaptation, increase the cross-sectional area of skeletal muscle and muscle hypertrophy, and promote muscle fibre and motor unit recruitment. Whereas endurance exercise promotes mitochondrial biogenesis, aerobic capacity, and energy utilisation, activating oxidative metabolism-related pathways to improve skeletal muscle metabolism and function. This review describes the effects of different exercise modes through the gut-muscle axis and how they act through mitochondria in ageing to define the current state of the field and issues requiring resolution.

Multi-omics analysis of nitrifying sludge under carbon disulfide stress: Nitrification performance and molecular mechanisms.

Carbon disulfide (CS2) is a widely used enzyme inhibitor with cytotoxic properties, commonly employed in viscose fibers and cellophane production due to its non-polar characteristics. In industry, CS2 is often removed by aeration, however, residual CS2 may enter the wastewater treatment plants, impacting the performance of nitrifying sludge. Currently, there is a notable dearth of research on the response of nitrifying sludge to CS2-induced stress. This study delves into the alterations in the performance of nitrifying sludge under short-term and long-term CS2 stress, scrutinizes the toxic effects of CS2 on microbial cells, elucidates the succession of microbial community structure, and delineates changes in microbial metabolic products. The findings from short-term CS2 stress revealed that low concentrations of CS2 induced oxidative stress damage, which was subsequently repaired in cells. However, at concentrations of 100-200 mg/L, CS2 inhibited reactive oxygen species, superoxide dismutase, and catalase, which are associated with metabolic and antioxidant activities. The inhibition of nitrite oxidoreductase activity by high concentrations of CS2 was attributed to its impact on the enzyme's conformation. Prolonged CS2 stress resulted in an increase in the secretion of soluble extracellular polymeric substances in sludge, while CS2 was assimilated into sulfate. The analysis of sludge microbial community structure revealed a decline in the relative abundance of Rhodanobacter, which is associated with nitrification, and an increase in Sinomonas, involved in sulfur oxidation. Metabolite analysis results demonstrated that high concentrations of CS2 affect pantothenate and CoA biosynthesis, purine metabolism, and glutathione metabolism. This study elucidated the microbial response mechanism of nitrifying sludge under short-term and long-term CS2 stress. It also clarified the composition and function of microbial ecosystems, and identified key bacterial species and metabolites. It provides a basis for future research to reduce CS2 inhibition through approaches such as the addition of metal ions, the selection of efficient CS2-degrading strains, and the modification of strain metabolic pathways.

Paxbp1 is indispensable for the maintenance of peripheral CD4 T cell homeostasis.

The size and condition of the peripheral CD4 T cell population determine the capacity of the immune response. Under homeostatic conditions, the size of the peripheral CD4 T cell population is maintained through turnover and survival. However, the underlying mechanisms remain inadequately understood. Here, we observed a significant decrease in the percentage of CD4 T cells in the periphery following the targeted deletion of the Paxbp1 gene in mouse T cells. In the absence of Paxbp1, naïve CD4 T cells displayed reduced surface interleukin-7 receptor levels and a decreased capacity to respond to survival signals mediated by interleukin-7. In addition, naïve CD4 T cells deficient in Paxbp1 demonstrated impaired T cell antigen receptor signalling, compromised cell cycle entry, decreased proliferation, and increased apoptosis following stimulation, all of which contributed to the reduction in the number of peripheral CD4 T cells. Therefore, our study highlights the indispensable role of Paxbp1 in maintaining peripheral CD4 T cell homeostasis.

DNA methylase 1 influences temperature responses and development in the invasive pest Tuta absoluta.

DNA methylase 1 (Dnmt1) is an important regulatory factor associated with biochemical signals required for insect development. It responds to changes in the environment and triggers phenotypic plasticity. Meanwhile, Tuta absoluta Meyrick (Lepidoptera: Gelechiidae)-a destructive invasive pest-can rapidly invade and adapt to different habitats; however, the role of Dnmt1 in this organism has not been elucidated. Accordingly, this study investigates the mechanism(s) underlying the rapid adaptation of Tuta absoluta to temperature stress. Potential regulatory genes were screened via RNAi (RNA interference), and the DNA methylase in Tuta absoluta was cloned by RACE (Rapid amplification of cDNA ends). TaDnmt1 was identified as a potential regulatory gene via bioinformatics; its expression was evaluated in response to temperature stress and during different development stages using real-time polymerase chain reaction. Results revealed that TaDnmt1 participates in hot/cold tolerance, temperature preference and larval development. The full-length cDNA sequence of TaDnmt1 is 3765 bp and encodes a 1254 kDa protein with typical Dnmt1 node-conserved structural features and six conserved DNA-binding active motifs. Moreover, TaDnmt1 expression is significantly altered by temperature stress treatments and within different development stages. Hence, TaDnmt1 likely contributes to temperature responses and organismal development. Furthermore, after treating with double-stranded RNA and exposing Tuta absoluta to 35°C heat shock or -12°C cold shock for 1 h, the survival rate significantly decreases; the preferred temperature is 2°C lower than that of the control group. In addition, the epidermal segments become enlarged and irregularly folded while the surface dries up. This results in a significant increase in larval mortality (57%) and a decrease in pupation (49.3%) and eclosion (50.9%) rates. Hence, TaDnmt1 contributes to temperature stress responses and temperature perception, as well as organismal growth and development, via DNA methylation regulation. These findings suggest that the rapid geographic expansion of T absoluta has been closely associated with TaDnmt1-mediated temperature tolerance. This study advances the research on 'thermos Dnmt' and provides a potential target for RNAi-driven regulation of Tuta absoluta.

Predicting the potential mechanism of radix chimonanthi pracecocis in treating osteoarthritis by network pharmacology analysis combined with experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Chimonanthi Pracecocis (RCP), also known as Tiekuaizi, widely used by the Miao community in Guizhou, exhibits diverse biological activities and holds promise for the treatment of osteoarthritis (OA). However, there is a lack of contemporary pharmacological research in this area. AIMS OF THE STUDY: This study aims to explore the potential of targets and mechanisms of RCP in the treatment of OA. MATERIALS AND METHODS: The chemical components of RCP were identified using UPLC-MS/MS, and active components were determined based on the Lipinski rule. RCP and OA-related targets were retrieved from public databases such as TCMSP and GeneCards. Network pharmacology approaches were employed to identify key genes. The limma package (version 3.40.2) in R 4.3.2 was used to screen for differentially expressed genes (DEGs) between OA and healthy individuals in GSE82107. DEGs were analyzed using an independent sample t-test and receiver operating characteristic analysis in GraphPad Prism 9.5.1. Additionally, molecular docking (SYBYL2.1.1) was used to analyze the binding interactions between the active components and target proteins. Finally, we established a papain-induced osteoarthritis (OA) rat model and treated it with RCP aqueous extract by gavage. We validated relevant indicators using real-time fluorescence quantitative polymerase chain reaction, Western blot, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: Seven active components and 53 targets were identified. The results of GO and KEGG enrichment analyses confirmed the significant role of RCP in the regulation of pyroptosis. Hypoxia-inducible factor-1α (HIF-1α) was identified as a key gene involved in the main biological functions. Molecular docking analysis revealed that Praecoxin, Isofraxidin, Esculin, and Naringenin can bind to the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) (T-Score >5). Additionally, Praecoxin can bind to HIF-1α (T-Score >5). In vivo experiments demonstrated that RCP significantly affects the NLRP3 inflammasome, which is regulated by the HIF-1α pathway. RCP inhibited pyroptosis and reduced synovial inflammation. CONCLUSIONS: This study confirmed the efficacy of RCP aqueous extract in the treatment of OA and identified seven active components (esculin, dihydrokaempferol, naringenin, praecoxin, carnosol, hydroxyvalerenic acid, isofraxidin) that may play an anti-pyroptosis role in the treatment of OA by downregulating the expression of HIF-1α and NLRP3 inflammasome.

Chemokines and Their Receptors: Predictors of Therapeutic Potential in Tumor Microenvironment on Esophageal Cancer.

Esophageal carcinoma (ESCA) is an aggressive solid tumor. The 5-year survival rate for patients with ESCA is estimated to be less than 20%, mainly due to tumor invasion and metastasis. Therefore, it is urgent to improve early diagnostic tools and effective treatments for ESCA patients. Tumor microenvironment (TME) enhances the ability of tumor cells to proliferate, migrate, and escape from the immune system, thus promoting the occurrence and development of tumor. TME contains chemokines. Chemokines consist of four major families, which are mainly composed of CC and CXC families. The main purpose of this review is to understand the CC and CXC chemokines and their receptors in ESCA, to improve the understanding of tumorigenesis of ESCA and determine new biomarkers for the diagnosis and prognosis of ESCA. We reviewed the literature on CC and CXC chemokines and their receptors in ESCA identified by PubMed database. This article introduces the general structures and functions of CC, CXC chemokines and their receptors in TME, as well as their roles in the progress of ESCA. Chemokines are involved in the development of ESCA, such as cancer cell invasion, metastasis, angiogenesis, and radioresistance, and are key determinants of disease progression, which have a great impact on patient prognosis and treatment response. In addition, a full understanding of their mechanism of action is essential to further verify that these chemokines and their receptors may serve as biomarkers or therapeutic targets of ESCA.

Tandemly expanded OR17b in Himalaya ghost moth facilitates larval food allocation via olfactory reception of plant-derived tricosane.

Herbivorous insects utilize intricate olfactory mechanisms to locate food plants. The chemical communication of insect-plant in primitive lineage offers insights into evolutionary milestones of divergent olfactory modalities. Here, we focus on a system endemic to the Qinghai-Tibetan Plateau to unravel the chemical and molecular basis of food preference in ancestral Lepidoptera. We conducted volatile profiling, neural electrophysiology, and chemotaxis assays with a panel of host plant organs to identify attractants for Himalaya ghost moth Thitarodes xiaojinensis larvae, the primitive host of medicinal Ophiocordyceps sinensis fungus. Using a DREAM approach based on odorant induced transcriptomes and subsequent deorphanization tests, we elucidated the odorant receptors responsible for coding bioactive volatiles. Contrary to allocation signals in most plant-feeding insects, T. xiaojinensis larvae utilize tricosane from the bulbil as the main attractant for locating native host plant. We deorphanized a TxiaOR17b, an indispensable odorant receptor resulting from tandem duplication of OR17, for transducing olfactory signals in response to tricosane. The discovery of this ligand-receptor pair suggests a survival strategy based on food location via olfaction in ancestral Lepidoptera, which synchronizes both plant asexual reproduction and peak hatch periods of insect larvae.

Changes of college students' psychological stress during the COVID-19 pandemic in China: A two-wave repeated survey.

COVID-19 has posed unprecedented challenges to the mental health of college students worldwide. We examined the trends in students' stress levels during and after China's first wave of COVID-19 outbreaks by analyzing their demographics, behavior, mental health status, career confidence, and Chinese Perceived Stress Scale (CPSS) scores. Our findings indicate an increase in students' stress levels since the COVID-19 onset, with more students experiencing higher stress levels after the first outbreak than during it (OR = 2.03, 95% CI 1.79, 2.30). Several factors were identified as being associated with higher CPSS scores, including higher class levels, residence in rural or town areas, low family income, and lack of familiarity with COVID-19, among others. Our study highlighted the urgency of developing and implementing effective strategies to cope with students' stress during and after a global pandemic.

An "All-In-One" Immunomodulator-Engineered Clinical Translatable Immunotherapy of Advanced Hepatocellular Carcinoma.

Clinical treatment of advanced hepatocellular carcinoma (HCC) remains a significant challenge. Utilizing 1-bromoacetyl-3,3-dinitroazetidine (RRx-001) to downregulate the expression of innate immune checkpoint molecule, cluster of differentiation 47 (CD47), provides a powerful means for treating advanced HCC containing abundant immunosuppressive macrophages. Herein engineering of a previously optimized Doxorubicin (DOX)-delivery nanoplatform based on sodium alginate is reported to further co-deliver RRx-001 (biotinylated aldehyde alginate-doxorubicin micelle prodrug nanoplatform, BEA-D@R) for efficient immunotherapy of advanced HCC. This groundbreaking  technique reveals the "all-in-one" immunotherapeutic functionalities of RRx-001. Besides the previously demonstrated functions of downregulating CD47 expression and increasing reactive nitrogen species (RNS) generation, another key function of RRx-001 for downregulating the expression of the adaptive immune checkpoint molecule programmed cell death 1 ligand 1 (PDL1) is first uncovered here. Combined with the reactive oxygen species (ROS) generation and an upregulated "eat me" signal level of DOX, BEA-D@R collectively increases RNS generation, enhances T-cell infiltration, and maximizes macrophage phagocytosis, leading to an average of 40% tumor elimination in a mice model bearing an initial tumor volume of ≈300 mm3 that mimics advanced HCC. Overall, the "all-in-one" immunotherapeutic functionalities of a clinical translatable nanoplatform are uncovered for enhanced immunotherapy of advanced HCC.

A Joint State and Fault Estimation Scheme for State-Saturated System with Energy Harvesting Sensors.

In this article, the issue of joint state and fault estimation is ironed out for delayed state-saturated systems subject to energy harvesting sensors. Under the effect of energy harvesting, the sensors can harvest energy from the external environment and consume an amount of energy when transmitting measurements to the estimator. The occurrence probability of measurement loss is computed at each instant according to the probability distribution of the energy harvesting mechanism. The main objective of the addressed problem is to construct a joint state and fault estimator where the estimation error covariance is ensured in some certain sense and the estimator gain is determined to accommodate energy harvesting sensors, state saturation, as well as time delays. By virtue of a set of matrix difference equations, the derived upper bound is minimized by parameterizing the estimator gain. In addition, the performance evaluation of the designed joint estimator is conducted by analyzing the boundedness of the estimation error in the mean-squared sense. Finally, two experimental examples are employed to illustrate the feasibility of the proposed estimation scheme.

Improved Immune Response for Colorectal Cancer Therapy Triggered by Multifunctional Nanocomposites with Self-Amplifying Antitumor Ferroptosis.

Ferroptosis, as a type of regulated cell death, can trigger the release of damage-associated molecular patterns from cancer cells and lead to the enhancement of immune recognition. Fenton reaction-mediated chemodynamic therapy could initiate ferroptosis by generating lipid peroxides, but its efficiency would be greatly restricted by the insufficient H2O2 and antioxidant system within the tumor. Herein, this work reports the successful preparation of H2O2 self-supplied and glutathione (GSH)-depletion therapeutic nanocomposites (Cu2O@Au) through in situ growth of Au nanoparticles on the surface of cuprous oxide (Cu2O) nanospheres. Upon delivery into cancer cells, the released Cu2O could consume endogenous H2S within colorectal cancer cells to form Cu31S16 nanoparticles, while the released Au NPs could catalyze glucose to generate H2O2 and gluconic acid. The self-supplying endogenous H2O2 and lower acidity could amplify the Cu ion-induced Fenton-like reaction. Meanwhile, the consumption of glucose would reduce GSH generation by disrupting the pentose phosphate pathway. Additionally, the Cu2+/Cu+ catalytic cycle promotes the depletion of GSH, leading to lipid peroxide accumulation and ferroptosis. It was found that the onset of ferroptosis triggered by Cu2O@Au could initiate immunologic cell death, promote dendritic cell maturation and T-cell infiltration, and finally enhance the antitumor efficacy of the PD-L1 antibody. In summary, this collaborative action produces a remarkable antitumor effect, which provides a promising treatment strategy for colorectal cancer.