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Introduction: Light-harvesting chlorophyll a/b-binding (LHCB) protein complexes of photosystem II are integral to the formation of thylakoid structure and the photosynthetic process. They play an important role in photoprotection, a crucial process in leaf development under low-temperature stress. Nonetheless, potential key genes directly related to low-temperature response and albino phenotype have not been precisely identified in tea plant. Moreover, there are no studies simultaneously investigating multiple albino tea cultivars with different temperature sensitivity. Objectives: The study aimed to clarify the basic characteristics of CsLHCB gene family members, and identify critical CsLHCB genes potentially influential in leaf color phenotypic variation and low-temperature stress response by contrasting green and albino tea cultivars. Concurrently, exploring the differential expression of the CsLHCB gene family across diverse temperature-sensitive albino tea cultivars. Methods: We identified 20 putative CsLHCB genes according to phylogenetic analysis. Evolutionary relationships, gene duplication, chromosomal localization, and structures were analyzed by TBtools; the physiological and biochemical characteristics were analyzed by protein analysis websites; the differences in coding sequences and protein accumulation in green and albino tea cultivars, gene expression with maturity were tested by molecular biology technology; and protein interaction was analyzed in the STRING database. Results: All genes were categorized into seven groups, mapping onto 7 chromosomes, including three tandem and one segmental duplications. They all own a conserved chlorophyll A/B binding protein domain. The expression of CsLHCB genes was tissue-specific, predominantly in leaves. CsLHCB5 may play a key role in the process of leaf maturation and senescence. In contrast to CsLHCB5, CsLHCB1.1, CsLHCB2, and CsLHCB3.2 were highly conserved in amino acid sequence between green and albino tea cultivars. In albino tea cultivars, unlike in green cultivars, the expression of CsLHCB1.1, CsLHCB1.2, and CsLHCB2 was down-regulated under low-temperature stress. The accumulation of CsLHCB1 and CsLHCB5 proteins was lower in albino tea cultivars. Greater accumulation of CsLHCB2 protein was detected in RX1 and RX2 compared to other albino cultivars. Conclusions: CsLHCB1.1, CsLHCB1.2, and CsLHCB2 played a role in the response to low-temperature stress. The amino acid sequence site mutation of CsLHCB5 would distinguish the green and albino tea cultivars. The less accumulation of CsLHCB1 and CsLHCB5 had a Chl influence on albino leaves. Albino cultivars more sensitive to temperature exhibited lower CsLHCB gene expression. CsLHCB2 may serve as an indicator of temperature sensitivity differences in albino tea cultivars. This study could provide a reference for further studies of the functions of the CsLHCB family and contribute to research on the mechanism of the albino in tea plant.

Global food loss and waste are significant challenges in the food system, critical to addressing food insecurity and national security in the U.S. Upcycled food, which reduces waste at the source, is a promising solution. Social media offers both opportunities and challenges for communicating food benefits. This study examines publicly available data from Instagram, Facebook, and Twitter of a non-profit organization Upcycled Food Association (UFA) using content analysis and machine learning techniques. The analysis revealed that social media posts focused on promoting food waste awareness and benefits related to sustainability, health, and the economy, with environmental information being prioritized. UFA employs diverse impact information frames and uses positive emotion framing to increase food waste awareness and empower consumers by highlighting the impact of their purchasing power. Communication strategies are tailored to the unique characteristics of each social media platform and its users. We recommend social media initiatives continue emphasizing food waste awareness and upcycling, alongside increasing health information to encourage upcycled food consumption. Diverse strategies with diverse benefits and tailored to each platform's characteristics and sociodemographic groups are recommended. Future research can explore efficient topic modeling methods in larger datasets in social media analysis.

Gene-editing technology provides promising opportunities for livestock industries by enabling precise genetic modifications that enhance desirable traits such as increased disease resistance, heat tolerance, and nutritional quality. With gene-edited beef products entering the market soon, understanding consumers’ acceptance is critical. Using structural equation modeling, the study aimed to determine how key psychological and social factors influence U.S. consumers’ attitudes toward gene editing and their behavioral intentions toward ground beef from gene-edited cattle. Results indicate that knowledge, subjective social norms, and perceived benefits positively influenced attitudes, while perceived risks and food technology neophobia negatively influenced attitudes. Subjective social norms, perceived benefits, and attitudes positively influenced behavioral intentions, while perceived risks and food technology neophobia negatively influenced intentions. Attitudes acted as a partial mediator, significantly mediating the effects of subjective social norms, perceived benefits, perceived risks, and food technology neophobia on behavioral intentions. Improving consumers’ behavioral intentions toward ground beef from gene-edited cattle hinges on cultivating more favorable attitudes toward the technology. Thus, collaborative efforts by scientists, producers, policymakers, extension agents, and agricultural communicators should seek to increase consumers’ perceived benefits and improve subjective social norms, as these factors were most influential.

Traditional Chinese Medicine (TCM) formulations serve as a multi-component pharmacological combination therapy with various potential targets and have collected extensive knowledge regarding the in vivo efficacy of treating cardiovascular disorders in clinical practice for thousands of years. However, the obscurity of the chemicals and the molecular mechanisms are impediments to their continued growth and globalization. Therefore, new modern medications based on the combination of beneficial TCM components with precise clinical efficacy are required. The goal of this study was to find the best combination of Achyranthes bidentata Blume (AB) and Paeonia lactiflora Pall. (PL) for hypertension with liver yang hyperactivity (HLYH). The integrated research consisting of principal component analysis (PCA), metabolomics, microbiology, and weighted correlation network analysis (WGCNA) were used to find the optimal combination of AB-PL combinations and reveal the mechanism of action. The result showed AB-PL (2:3) had a substantial protective impact on HLYH, as shown by lower blood pressure, improved liver yang hyperactivity, reduced cardiac remodeling and malondialdehyde (MDA), and increased NO content. Furthermore, the essential elements for AB-PL reducing hypertension may be related to 135 metabolites and 23 microorganisms. In conclusion, our findings support the efficacy of herbal remedies in the treatment of hypertension and provide some pharmacological evidence for the ongoing development of novel modern Chinese drugs for cardiovascular disorders.

Prior research has explored the relationship between occupational exposure to nickel and lung function. Nonetheless, there is limited research examining the correlation between blood nickel levels and lung function among young adults in the general population. The metabolomic changes associated with nickel exposure have not been well elucidated. On August 23, 2019, we enrolled 257 undergraduate participants from the Chinese Undergraduates Cohort to undergo measurements of blood nickel levels and lung function. The follow-up study was conducted in May 2021. A linear mixed-effects model was employed to assess the relationship between blood nickel levels and lung function. We also conducted stratified analyses by home address. In addition, in order to explore the biological mechanism of lung function damage caused by nickel exposure, we performed metabolomic analyses of baseline serum samples (N = 251). Both analysis of variance and mixed linear effect models were utilized to assess the impact of blood nickel exposure on metabolism. Our findings from cross-sectional and cohort analyses revealed a significant association between blood nickel levels and decreased forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) among young adults in the general population. Furthermore, we found stronger associations in urban areas. In metabolomics analysis, a total of nine metabolites were significantly changed under blood nickel exposure. The changed metabolites were mainly enriched in six pathways including carbohydrate, amino acid, and cofactor vitamin metabolism. These metabolic pathways involve inflammation and oxidative stress, indicating that high concentrations of nickel exposure can cause inflammation and oxidative stress by disrupting the above metabolism of the body.

Decellularized tissue-engineered vascular grafts (dTEVGs) exhibit superior biocompatibility, anti-infection properties and repair potential, contributing to better patency and making them a more ideal choice for arteriovenous grafts (AVGs) in hemodialysis compared to chemically synthesized grafts. However, the unsatisfactory reendothelialization and smooth muscle remodeling of current dTEVGs limit their advantages. In this study, we investigated the use of elastase to improve the porosity of elastic fiber layers in dTEVGs, aiming to promote cell infiltration and achieve superior reendothelialization and smooth muscle remodeling. Our findings revealed that elastase treatment induced scattered cracks and holes in the elastic fiber layers of dTEVGs. Porous dTEVGs demonstrated increased cell infiltration in rat subcutaneous tissue. In the rat AVG models, mildly elastase-treated dTEVGs significantly improved cell infiltration and graft remodeling, including adequate smooth muscle cell (SMC) repopulation, impressive reendothelization and regeneration of the extracellular matrix, without stenosis, dilation or disintegration of the grafts. This study demonstrates that porous dTEVGs promote reendothelization, smooth muscle remodeling and extracellular matrix regeneration while retaining a stable graft structure, enhancing durability and puncture resistance in hemodialysis.

Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults. The Cr exposure-related metabolomic changes are not well elucidated. This study recruited 608 students from a university in Shandong Province, China in 2019. We used cohort design fitted with linear mixed-effects models to assess the association between blood Cr concentration and lung function. In addition, we performed metabolomic and lipidomic analyses of baseline serum samples (N = 582) using liquid chromatography-mass spectrometry. Two-step statistical analysis (analysis of variance and mixed-linear effect model) was used to evaluate the effect of blood Cr exposure on metabolites. We found that blood Cr was associated with decreased lung function in young adults. Each 2-fold increase in blood Cr concentrations was significantly associated with decreased FEV1 and FVC by 35.26 mL (95 % CI: −60.75, −9.78) and 38.56 mL (95 % CI: −66.60, −10.51), respectively. In the metabolomics analysis, blood Cr exposure was significantly associated with 14 key metabolites. The changed metabolites were mainly enriched in six pathways including lipid metabolism, amino acid metabolism, and cofactor vitamin metabolism. Blood Cr may affect lung function through oxidative stress and inflammation related pathways.

Wind power exhibits low controllability and is situated in dispersed geographical locations, presenting complex coupling and aggregation characteristics in both temporal and spatial dimensions. When large-scale wind power is integrated into the power grid, it will bring a significant technical challenge: the highly variable nature of wind power poses a threat to the safe and stable control of the power, frequency, and voltage in the power system. Simultaneously, the model predictive control (MPC) technology provides more opportunities for investigating control issues related to large-scale wind power integration in power systems. This paper provides a timely and systematic overview of the applications of MPC in the field of wind power for the first time, innovatively embedding MPC technology into multi-level (e.g., wind turbines, wind farms, wind power cluster, and power grids) and multi-objective (e.g., power, frequency, and voltage) control. Firstly, the basic concept and classification criteria of MPC are developed, and the available modeling methods in wind power are carefully compared. Secondly, the application scenarios of MPC in multi-level and multi-objective wind power control are summarized. Finally, how to use a variety of optimization algorithms to solve these models is discussed. Based on the broad review above, we summarize several key scientific issues related to predictive control and discuss the challenges and future development directions in detail. This paper details the role of MPC technology in multi-level and multi-objective control within the wind power sector, aiming to help engineers and scientists understand its substantial potential in wind power integration in power systems.

Background: This study investigated the effects of purple sweet potato anthocyanins (PSPA) in a type 2 diabetes mellitus (T2DM) mouse model. Methods: Sixty-five male mice were randomly divided into one control group and four experimental groups, which were fed with a high-fat diet and intraperitoneally injected with streptozotocin (STZ) to induce T2DM. The model mice were treated with 0 (M), 227.5 (LP), 455 (MP), or 910 (HP) mg/kg PSPA for ten days. ELISA, 16S rRNA sequencing, and hematoxylin and eosin staining were used to assess blood biochemical parameters, gut microbial composition, and liver tissue structure, respectively. Results: The FBG concentration was significantly decreased in the LP (6.32 ± 1.05 mmol/L), MP (6.32 ± 1.05 mmol/L), and HP (5.65 ± 0.83 mmol/L) groups; the glycosylated hemoglobin levels were significantly decreased in the HP group (14.43 ± 7.12 pg/mL) compared with that in the M group (8.08 ± 1.04 mmol/L; 27.20 ± 7.72 pg/mL; P

Background: Chronic subdural hematoma (CSDH) is a prevalent form of intracranial haemorrhage encountered in neurosurgical practice, and its incidence has notably risen in recent years. Currently, there is a lack of studies that have comprehensively classified the cells present in hematomas removed during surgery, and their correlation with CSDH recurrence remains elusive. This study aims to analyse the subcellular populations and occupancy levels within peripheral blood. Methods: This study analyses the subcellular populations and occupancy levels within peripheral blood and postoperatively removed hematomas by single-cell sequencing and attempts to analyse the effect of different cell occupancies within peripheral blood and intraoperatively removed hematomas on CSDH. Results: The single-cell sequencing results showed that the cells were classified into 25 clusters by differential gene and UMAP dimensionality reduction clustering analyses and further classified into 17 significant cell populations by cell markers: pDCs, CD8 T cells, CD4 T cells, MigDCs, cDC2s, cDC1s, plasma cells, neutrophils, naive B cells, NK cells, memory B cells, M2 macrophages, CD8 Teffs, CD8 MAIT cells, CD4 Tregs, CD19 B cells, and monocytes. Further research showed that the presence of more cDC2 and M2 macrophages recruited at the focal site in patients with CSDH and the upregulation of the level of T-cell occupancy may be a red flag for further brain damage. ROS, a marker of oxidative stress, was significantly upregulated in cDC2 cells and may mediate the functioning of transcription proteins of inflammatory factors, such as NFκB, which induced T cells' activation. Moreover, cDC2 may regulate M2 macrophage immune infiltration and anti-inflammatory activity by secreting IL1β and binding to M2 macrophage IL1R protein. Conclusion: The detailed classification of cells in the peripheral blood and hematoma site of CSDH patients helps us to understand the mechanism of CSDH generation and the reduction in the probability of recurrence by regulating the ratio of cell subpopulations.

Aims: Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current investigation aims to evaluate BMX's impact on retinal I/R injury and clarify its implied mechanism of action. Main methods: This study utilized male and female systemic BMX knockout (BMX−/−) mice to conduct experiments. The utilization of Western blot assay and immunofluorescence labeling techniques was employed to investigate variations in the expression of protein and tissue localization. Histomorphological changes were observed through H&E staining and SD-OCT examination. Visual function changes were assessed through electrophysiological experiments. Furthermore, apoptosis in the retina was identified using the TUNEL assay, as well as the ELISA technique, which has been utilized to determine the inflammatory factors level. Key findings: Our investigation results revealed that the knockdown of BMX did not yield a significant effect on mouse retina. In mice, BMX knockdown mitigated the negative impact of I/R injury on retinal tissue structure and visual function. BMX knockdown effectively reduced apoptosis, suppressed inflammatory responses, and decreased inflammatory factors subsequent to I/R injury. The outcomes of the current investigation revealed that BMX knockdown partially protected the retina through downregulating phosphorylation of AKT/ERK/STAT3 pathway. Significance: Our investigation showed that BMX−/− reduces AKT, ERK, and STAT3 phosphorylation, reducing apoptosis and inflammation. Thus, this strategy protected the retina from structural and functional damage after I/R injury.

To better understand the effect of oxygen levels in the storage environment on peanut protein oxidation and explore the mechanism, the functional properties and the oxidation degree of peanut proteins extracted from peanuts under conventional storage (CS), nitrogen modified atmosphere storage (NS, hypoxic) and re-aeration storage (RS) were investigated. Metabolomics and proteomics were employed to analyze peanut’s response to hypoxic/re-aeration storage environment. The results showed that NS retarded the decline of the functional properties and the oxidation of peanut proteins, while the process were accelerated after re-aeration. That was the result of the metabolic changes of peanuts under different storage environments. The omics results presented the decreased (NS)/increased (RS) levels of the antioxidant-related proteins acetaldehyde dehydrogenase and glutathione S-transferase, and the inhibition (NS)/activation (RS) of metabolic pathways such as the TCA cycle and the pentose phosphate pathway. This study provided a reference for the re-aeration storage of other agricultural products.

Background: Tuberculosis continues to be a significant public health concern in China, particularly among the elderly population. This study aimed to assess the risk factors of tuberculosis among elderly individuals in China through a cohort study, focusing on this high-risk population. Methods: The population-based census was strategically designed to cover diverse regions and demographics across the city. The survey captured demographic and lifestyle information, as well as a clinical examination. Participants were prospectively followed up over a specified duration to monitor the incidence of tuberculosis cases. Results: After a follow-up period of more than 7 years, 246 individuals developed tuberculosis, resulting in an incidence rate of 92.21 per 100,000 person-years (95 % CI 81.2–104.3). In multivariate analysis, the following factors were found to have significant associations with active tuberculosis. Increasing age correlated with a higher risk of active tuberculosis (AHR = 1.03 per 1-year increase in age, 95%CI: 1.01, 1.04, P

Summary: Patients with HNF1A variants may develop liver steatosis, while the underlying mechanism is still unclear. Here, we established a mouse model carrying the dominant-negative HNF1α P291fsinsC mutation (hHNF1Amut/-) and found that the mutant mice developed liver steatosis spontaneously under the normal chow diet. Transcriptome analysis showed significant upregulation of Cfd and other genes related to innate immune response in the liver of hHNF1Amut/- mice. The changes in lipid metabolism and complement pathways were also confirmed by proteomics. We demonstrated that HNF1α inhibited CFD expression in hepatocytes, and the P291fsinsC mutant could reverse this inhibitory effect. Furthermore, the suppression of CFD with specific inhibitor or siRNAs reduced triglyceride levels in hepatocytes, suggesting that CFD regulated hepatocyte lipid deposition. Our results demonstrate that the HNF1α P291fsinsC mutant promotes hepatic steatosis and inflammation by upregulating CFD expression, and targeting CFD may delay the progression of nonalcoholic fatty liver disease.

Summary: The hypothalamus, as a vital brain region for endocrine and metabolism regulation, undergoes functional disruption during obesity.The anti-aging effect of metformin has come into focus. However, whether it has the potential to ameliorate hypothalamic aging and dysfunction in the obese state remains unclear. In this study, obese mice were utilized to investigate the effects of metformin on the hypothalamus of obese mice. According to the results, metformin treatment resulted in improved insulin sensitivity, reduced blood glucose and lipid levels, as well as attenuation of hypothalamic aging, demonstrated by decreased SA-β-gal staining and downregulation of senescence markers. Additionally, metformin decreased the expression of endoplasmic reticulum stress-related proteins in neurons and reduced the inflammatory response triggered by microglia activation. Further mechanistic analysis revealed that metformin inhibited the expression and activation of STING and NLRP3 in microglia. These results reveal a possible mechanism by which metformin ameliorates hypothalamic aging.

African swine fever (ASF) is the most devastating disease caused by the African swine fever virus (ASFV), impacting the pig industry worldwide and threatening food security and biodiversity. Although two vaccines have been approved in Vietnam to combat ASFV, the complexity of the virus, with its numerous open reading frames (ORFs), necessitates a more diverse vaccine strategy. Therefore, we focused on identifying and investigating the potential vaccine targets for developing a broad-spectrum defense against the virus. This study collected the genomic and/or transcriptomic data of different ASFV strains, specifically from in vitro studies, focusing on comparisons between genotypes I, II, and X, from the National Center for Biotechnology Information (NCBI) database. The comprehensive analysis of the genomic and transcriptomic differences between high- and low-virulence strains revealed six early genes, 13 late genes, and six short genes as potentially essential ORFs associated with high-virulence. In addition, many other ORFs (e.g., 14 multigene family members) are worth investigating. The results of this study provided candidate ORFs for developing ASF vaccines and therapies.

Plants have various cell types that respond to different environmental factors, and cell–cell communication is the fundamental process that controls these plant responses. The emergence of single-cell techniques provides opportunities to explore features unique to each cell type and construct a comprehensive cell–cell communication (CCC) network. Although the most current successes of CCC inference were achieved in animal research, computational methods can also be directly applied to plants. This review describes the current major models for cell–cell communication inference and summarizes the computational tools based on single-cell omics datasets. In addition, we discuss the limitations of plant cell–cell communication research and propose new directions to expand the field in meaningful ways.

Due to the fluctuation and intermittency of wind power resources, large-scale wind power integration brings serious challenges to power systems. Among the existing short-term forecasting methods, the accuracy and forecast period length can hardly meet the demand of power system economic dispatching and day-ahead power purchase markets. To further enhance the accuracy and increase the time scale, a short-term wind power forecasting (WPF) combined model based on numerical weather prediction (NWP) analysis is presented in this paper. First, according to the criterion of the minimum redundancy maximum relevance (mRMR) algorithm, several factors are sifted from the NWP multivariate data. Second, different characteristics of the factors are extracted, and weather patterns are divided into different types on the basis of these characteristics. Third, two deep learning models, Convolutional Neural Networks (CNN) and Long Short-Term Memory (LSTM), are applied for short-term WPF respectively under different weather types. Furthermore, the forecast results of the two models are combined using the Induced Ordered Weighted Average (IOWA) operator. The actual data collected from a wind farm in Northwest China are used to verify the conclusions. Results show that the proposed method can forecast wind power under different weather circumstances and outperform existing Radial Basis Function (RBF), Extreme Learning Machine (ELM) and Support Vector Machine (SVM)-based methods with respect to forecasting accuracy.

As a multifunctional DNA repair enzyme, human apurinic/apyrimidinic endonuclease 1 (APE1) plays a pivotal role in many cellular processes. In recent years, it has been recognized as a potential prognostic biomarker and a therapeutic target for many cancers and other diseases. In this work, we report a DNA/RNA hybrid-based fluorescent probe which allows rapid and high-throughput detection of APE1 in the nuclear, cytoplasmic, and mitochondrial extracts of different types of cultured cells without any purification steps. As a noncanonical substrate, the DNA/RNA hybrid probe possesses inherent specificity toward APE1 without the need of additional chemical modification. A substantial acceleration effect of the 3′-flanking mismatches enabled rapid digestion of the abasic sites in the DNA/RNA hybrid by APE1 at a comparable rate to those in natural double-stranded DNA. The hybrid probe showed adequately high sensitivity to the target enzyme (linear working range: 0.02–1.0 U/mL; detection limit: 0.01 U/mL) and superior resistance to interference from cellular proteins. The mechanism for the 3′-mismatch enhancement was also clarified via kinetic study and single-molecule fluorescence analysis. By using the probe, significantly varied subcellular distribution of APE1 in different cells were disclosed, showing the importance of quantitative measurement of APE1 activity in subcellular compartments for drug screening and evaluation of the treatment efficacy. The method was simple and robust, which offered an easily accessible molecular tool for high-throughput quantification of the subcellular APE1 activity. It may also facilitate the development of effective anticancer drugs.

Taking the external disturbances with unknown boundaries into consideration, this paper deals with the time-varying formation control problem of multiple quadrotors system based on static/dynamic event-triggered integral sliding mode control (ISMC) and adaptive sliding mode disturbance estimator (ASMDE). At first, two different position controllers, static event-triggered and dynamic event-triggered controllers, are proposed to deal with the time-varying formation problem of the multiple quadrotors system based on ISMC. The stability conditions are obtained through the Lyapunov theory. By the reverse proving method, it is also proved that there is no Zeno behavior in both static event-triggered position controller and dynamic event-triggered position controller. Then, the external disturbances are considered where the bounds of the perturbations are unknown. The ASMDE is applied to estimate the external disturbances, which increases the robustness of the multiple quadrotors system when applying the proposed methods. Next, the chattering free terminal sliding mode attitude controller for individual quadrotor is designed. Finally, the theoretical results are validated through numerical simulations.

Joint state and unknown input estimation for continuous–discrete stochastic systems can be classified into two types: with and without modeling of unknown inputs. This paper first proposes a recursive four-step Kalman filter for addressing the joint state and unknown input estimation of continuous–discrete stochastic systems and presents its stability conditions. Then, a theoretical analysis of the performances using the unknown input Kalman filters and an adaptive augmented Kalman filter is presented and validated using numerical simulations under different situations. Both the theory and simulation demonstrate that the adaptive augmented Kalman filters is a better option when addressing unknown inputs for continuous–discrete stochastic systems.

Summary: Canonical WNT pathway in mature adipocytes exacerbates obesity. In this study, we constructed UCP1-positive adipocytes-specific Ctnnb1 knockout mice (UBKO) and observed increased “browning” of white adipose tissue (WAT) following cold exposure or CL-316,243 administration compared to controls. UBKO mice also displayed increased energy expenditure. Furthermore, β-catenin (encoded by Ctnnb1) inhibited thermogenic genes expression in differentiated beige adipocytes and repressed Ucp1 expression at transcription level. Transcriptome analysis revealed UBKO mice treated with CL-316,243 had enhanced mitochondrial function and downregulated immune-related genes in epididymal WAT. Improved glucose tolerance and insulin sensitivity were observed in 50-week-old UBKO mice. Public datasets indicated that CTNNB1 expression was inversely correlated with several thermogenic genes expression in human adipose tissue/adipocytes and positively correlated with BMI or waist-hip ratio (WHR). We proposed that intervention of β-catenin in adipocytes could be an effective strategy to enhance energy expenditure and improve age-related metabolic performance.

Idiopathic pulmonary fibrosis (IPF) is a serious and fatal pulmonary inflammatory disease with an increasing incidence worldwide. The drugs nintedanib and pirfenidone, are listed as conditionally recommended drugs in the “Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”. However, these two drugs have many adverse reactions in clinical application. Salvianolic acid B (Sal B), a water-soluble component of Salvia miltiorrhiza, could alleviate bleomycin-induced peroxidative stress damage, and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease's progression. However, Sal B is poorly absorbed orally, and patient compliance is poor when administered intravenously. Therefore, there is an urgent need to find a new non-injection route of drug delivery. In this study, Sal B was used as model drug and l-leucine (LL) as excipient to prepare Sal B dry powder inhaler (Sal B-DPI) by spray drying method. Modern preparation evaluation methods were used to assess the quality of Sal B-DPI. Sal B-DPI is promising for the treatment of IPF, according to studies on pulmonary irritation evaluation, in vivo and in vitro pharmacodynamics, metabolomics, pharmacokinetics, and lung tissue distribution.

Summary: Background: Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy. Methods: We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667. Findings: We obtained data from 13 studies out of 40 that were considered eligible (N = 32,034 participants: 36% from countries with TB incidence rate ≥100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette–Guérin vaccine (BCG) status (15 mm if BCG vaccinated and 5 mm if not [TST5/15 mm]) at 2.88 (95% CI 1.69–4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97–8.75). The difference was large in countries with TB incidence rate

Nitrogen modified atmosphere was an effective way to control pest infestation in grains. In this study, the quality changes of rice during nitrogen modified atmosphere packaging storage (N2-MAPS) were monitored. An un-targeted metabolomics method was used to detect the rice metabolites and explore the mechanism of N2-MAPS for delaying rice deterioration. In this study, two rice species were studied under N2-MAPS and conventional storage at 30 °C for 150 days. The quality changes of rice during storage were monitored. The results showed that N2-MAPS could retard the increase of fatty acid value and amylose content, and defer the decrease of enzyme activities. And N2-MAPS had no significant influence on texture characteristics of rice. The metabolomics results suggested some metabolites and pathways were affected by N2-MAPS and revealed that N2-MAPS could protect rice cells from oxidative damage, maintain cell integrity and stability by regulating the metabolism to delay the rice deterioration.

Bee pollen, a beehive product collected from flowers by honeybees, contains over 250 biological substances, and has attracted increasing attention as a functional food. However, commercial bee pollen products are often multifloral, and samples from different countries vary significantly. There is no universal standard for objective quality assessment of bee pollen based on its chemical composition. Here, we report metabolomic analysis of 11 bee pollen samples from Spain, China, and Australia for quality control. The characteristics of the samples depend on the sucrose, nucleoside, amino acid, and flavanol concentrations. Bee pollen samples from Spain and Australia had higher sucrose and adenosine concentrations, whereas those from China had higher trigonelline, uridine, and cytidine concentrations. Interestingly, acetic acid was only detected in samples from China. These components can be used to identify the country of origin. The obtained profiles of the samples will contribute to universal standard development for bee pollen products.

The accuracy and enrichment rate of targeted drugs largely determine the clinical diagnosis and treatment effect. Therefore, the accuracy and enrichment rate of targeted drugs should be improved. We designed a visual diagnosis and treatment system based on hierarchical targeting. It consists of multifunctional magnetic nanoparticles and a bio magnetic material. Bio-magnet mediated primary targeting can effectively improve the drug enrichment rate in the target tissue. SNF peptide/epithelial cell adhesion molecule antibody mediated targeting liver cancer stem cells (LCSCs) (secondary target) can improve the accuracy of the treatment and its outcomes. Low intensity focused ultrasound irradiation can explode nanoparticles around LCSCs, which can cause physical damage to cells. The combination of released interferon gamma and its receptor (tertiary target) can be used to initiate chemotherapy and immunotherapy. Using the optical properties of Fe3O4 and the phase transformation ability of perfluoropentane, the system can enhance photoacoustic and ultrasonic molecular imaging enabling diagnosis and treatment visualization. Targeting LCSCs can accurately provide physical, chemical, and immune treatment of Hepatocellular carcinoma, making the therapeutic effect more effective and thorough. This system may provide a new method for a more accurate visual diagnosis and treatment of tumors.

Objective: To explore whether all individuals with diabetes are at an increased risk of tuberculosis or whether there are high-risk groups of diabetes patients. Methods: A population-based census was conducted in China, including 27 807 individuals. Risk factors for incident tuberculosis were investigated and participants included in the study were linked to the Tuberculosis Management Information System. Cox proportional hazards models adjusting for several variables were constructed in two steps. First, the incident rate of tuberculosis in individuals with/without diabetes was compared without any stratification by high body mass index (BMI). Second, two groups stratified by BMI were compared. Results: Over 7 years of follow-up, 108 individuals progressed to tuberculosis. In the multivariable Cox regression analysis, participants with diabetes had a 2.26 higher hazard (P = 0.017) of tuberculosis when compared to participants without diabetes. However, participants with a BMI >24 kg/m2 and diagnosed with diabetes had a similar risk as overweight participants without diabetes (P = 0.953), while diabetes with a BMI

Environmental sanitation of maternal contact during pregnancy is extremely important for the development of different fetal tissues and organs. In particular, during early pregnancy, any adverse exposure may cause abnormal fetal growth or inhibit the development of embryogenic organs. The potential risks of phthalate exposure, which affects the development of humans and animals, are becoming a serious concern worldwide. However, the specific molecular mechanism of di-(2-ethylhexyl) phthalate (DEHP)-induced cardiotoxicity in fetal mice remains unclear. In this study, animal models of DEHP gavage at concentrations of 250, 500, and 1000 mg/kg/day within 8.5–18.5 days of pregnancy were established. The cell proliferation, survival, and apoptosis rates were evaluated using CCK8, EdU, TUNEL and flow cytometry. The molecular mechanism was assessed via transcriptome sequencing, immunohistochemistry, immunofluorescence, reverse transcription-quantitative polymerase chain reaction, and Western blot analysis. In vivo, DEHP increased apoptosis, decreased Ki67 and CD31 expression, reduced heart weight and area, slowed down myocardial sarcomere development, and caused cardiac septal defect in fetal mice heart. Transcriptome sequencing showed that DEHP decreased NRG1 expression and downregulated the ErbB2/ErbB4-PI3K/AKT signaling pathway-related target genes. In vitro, primary cardiomyocytes were cultured with DEHP at a concentration of 150 μg/mL combined with ErbB inhibitor (AG1478, 10 μmol/L) and/or NRG1 protein (100 ng/mL) for 72 h. After DEHP intervention, the expression of NRG1 and the phosphorylation level of ErbB2, ErbB4, PI3K, and AKT decreased, and the apoptosis-related protein levels increased. Moreover, the apoptosis rate increased. After adding exogenous NRG1, the phosphorylation level of the NRG1/ERbB2/ERbB4-PI3K/AKT pathway increased, and the apoptosis-related protein levels decreased. Further, the apoptosis rate reduced. Interestingly, after exposure to DEHP and AG1478 + NRG1, the anti-apoptotic effect of NRG1 and cardiomyocyte proliferation decreased by inhibiting the NRG1/ERbB2/ERbB4-PI3K/AKT pathway. Hence, the NRG1-dependent regulation of the ERbB2/ERbB4-PI3K/AKT signaling pathway may be a key mechanism of DEHP-induced myocardial cytotoxicity.

Background & Aims: In short-bowel syndrome (SBS), inadequate intestinal adaptation is responsible for the majority of complications, including sepsis, liver failure, and death. In this study, we sought to further delineate the adaptive response to identify potential therapeutic targets. Methods: We performed a 75% small-bowel resection (SBR) or sham operation on C57Bl/6J wild-type (WT), lipocalin-2 (LCN2)-/-, and interleukin 22 (IL22)-/- mice. Exogenous IL22 was administered to SBR WT mice. Cecal fecal matter from SBR WT and SBR LCN2-/- mice were transplanted into germ-free mice. Intestinal permeability, inflammation, proliferation, and the microbiome were evaluated 1 week after surgery. CD4+IL22+ laminal propria lymphocytes were sorted by flow cytometry. Naïve T cells were polarized to T-helper cells with or without LCN2. Results: A 75% SBR in a mouse re-creates the increased intestinal permeability, enterocyte proliferation, and intestinal dysbiosis seen in SBS. LCN2 expression increases after 75% SBR, and this increase can be abrogated with broad-spectrum antibiotic treatment. LCN2-/- mice have less intestinal inflammation, increased IL22 expression, and greater adaptation as evidenced by less intestinal permeability, increased carbohydrate enzyme expression, less weight loss, and less dysbiosis after 75% SBR than WT mice. The proinflammatory and anti-adaptive effects of LCN2 can be transferred to germ-free mice via a fecal transplant. Administration of exogenous IL22 improves adaptation and restores the normal microbiome after 75% SBR in WT mice. Conclusions: LCN2 promotes inflammation and slows intestinal adaptation through changes in the microbiome and IL22 inhibition in a mouse SBS model. Strategies to reduce LCN2 may offer novel therapeutic approaches to enhance adaptation in SBS.

Background & Aims: Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by Toll-like receptor 4 (TLR4)-dependent intestinal inflammation and enterocyte death. Given that necroptosis is a proinflammatory cell death process that is linked to bacterial signaling, we investigated its potential role in NEC, and the mechanisms involved. Methods: Human and mouse NEC intestine were analyzed for necroptosis gene expression (ie, RIPK1, RIPK3, and MLKL), and protein activation (phosphorylated RIPK3). To evaluate a potential role for necroptosis in NEC, the effects of genetic (ie, Ripk3 knockout or Mlkl knockout) or pharmacologic (ie, Nec1s) inhibition of intestinal inflammation were assessed in a mouse NEC model, and a possible upstream role of TLR4 was assessed in Tlr4-deficient mice. The NEC-protective effects of human breast milk and its constituent milk oligosaccharides on necroptosis were assessed in a NEC-in-a-dish model, in which mouse intestinal organoids were cultured as either undifferentiated or differentiated epithelium in the presence of NEC bacteria and hypoxia. Results: Necroptosis was activated in the intestines of human and mouse NEC in a TLR4-dependent manner, and was up-regulated specifically in differentiated epithelium of the immature ileum. Inhibition of necroptosis genetically and pharmacologically reduced intestinal–epithelial cell death and mucosal inflammation in experimental NEC, and ex vivo in the NEC-in-a-dish system. Strikingly, the addition of human breast milk, or the human milk oligosaccharide 2 fucosyllactose in the ex vivo system, reduced necroptosis and inflammation. Conclusions: Necroptosis is activated in the intestinal epithelium upon TLR4 signaling and is required for NEC development, and explains in part the protective effects of breast milk. Keywords: Pediatrics, Premature, Organoid Model

Background: The health impact of short-term heat exposure is well documented. However, limited studies explored the association between life-time summer heat exposure and lung function. Objective: To examine the association between life-time summer heat exposure and lung function among young adults. Methods: We conducted a retrospective cohort study among 1928 college students in Shandong, China from September 4, 2020 to November 15, 2020. Life-time summer heat exposure for participants were estimated based on the nearest station meteorological data after the participant’s birth date and divided by their learning phases. Lung function indicators included forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). A multiple linear regression model was conducted to examine the associations between summer heat exposure and lung function. Stratification analysis by cooling facilities and respiratory diseases history were also conducted. Results: The study subjects had a slight majority of women (58.8%), age 19.2 ± 0.6 years. Each 1 °C increase in life-time summer mean temperature was associated with 1.07% [95% confidence interval (CI): −1.95–0.18%] decrease in FVC and 0.88% (95 %CI: −1.71, −0.05%) decrease in FEV1. Participants with respiratory diseases and non-cooling facility users were more susceptible to summer heat exposure. The usage of fan and air condition could effectively reduce the deleterious heat effects on lung function. Conclusion: Life-time summer heat exposure is significantly associated with the reduction of lung function in young adults. Cooling facilities are necessary for pre-school children to reduce heat effects. Fan and air-condition are effective cooling facilities, especially for people with respiratory diseases.

Fibrosis and cancer is described by some epidemiological studies as chronic stages of different disease conditions typically characterized by uncontrolled accumulation of extra-cellular matrix (ECM), thereby leading to inflammation of tissues and organ (lungs, heart, liver and kidney) dysfunction. It is highly prevalent, and contributes to increased mortality rate worldwide. Currently, the therapeutical approaches involving selected medications (bemcentinib, pirfenidone and nintedanib) obtained synthetically, and used in clinical practices for fibrosis and cancer management and treatment has shown to be unsatisfactorily, especially during progressive stages of the disease. With regards to finding a more potent, effective, and promising curative for fibrosis and cancer, there is need for continuous experimental studies universally. However, phytochemical constituents’ particularly phenolic compounds [Chlorogenic acid (CGA)] obtained from coffee, and coffee beans have been predominantly utilized in experimental studies, due to its multiple pharmacological properties against various disease forms. Considering its natural source alongside minimal toxicity level, CGA, a major precursor of coffee have gained considerable attention nowadays from researchers worldwide, owing to its wide, efficacious and beneficial action against fibrosis and cancer. Interestingly, the safety of CGA has been proven. Furthermore, numerous experimental studies have also deduced massive remarkable outcomes in the use of CGA clinically, as a potential drug candidate against treatment of fibrosis and cancer. In the course of this review article, we systematically discussed the beneficial contributions of CGA with regards to its source, absorption, metabolism, mechanistic effects, and molecular mechanisms against different fibrosis and cancer categorization, which might be a prospective remedy in the future. Moreover, we also highlighted CGA (in vitro and in vivo analytical studies) defensive effects against various disorders.

A novel CaCO3/graphitic carbon nitride (g-C3N4) photocatalyst was synthesized for the first time via a facile calcination method using CaCO3 and melamine as precursors. The as-prepared samples were characterized using various techniques, such as scanning and transmission electron microscopy, X-ray diffraction, Brunauer-Emmett-Teller analysis, as well as Fourier-transform infrared, X-ray photoelectron, photoluminescence, and UV–vis diffuse reflectance spectroscopy. The results of the experiments confirm the successful coupling of CaCO3 to g-C3N4. The photocatalytic activity of the synthesized CaCO3/g-C3N4 composites was evaluated by assessing their performance in the photocatalytic degradation of crystal violet (CV) in water under visible light irradiation. The analysis shows that CaCO3/g-C3N4 exhibits higher photocatalytic activity towards CV degradation (76.0%) than pristine g-C3N4 (21.6%) and CaCO3 (23.2%). Radical trapping and electron spin resonance experiments show that hydroxyl radicals (·OH) and holes (h+) are the key reactive species in the photocatalytic process. The enhanced photocatalytic activity of the composite is mainly attributed to the efficient separation rate of electron-hole pairs achieved through the incorporation of CaCO3. Keywords: CaCO3/g-C3N4, Calcination, Photocatalysis, Charge separation

ABSTRACT: The water-cooled ceramic breeder (WCCB) blanket is one of the blanket candidates for Chinese fusion engineering testing reactor (CFETR) and is being developed at the Institute of Plasma Physics, Chinese Academy of Sciences (ASIPP). This paper reviews design and evolution of the WCCB blanket for CFETR, and presents a new WCCB blanket design according to the latest CFETR core parameters (major and minor radii are R = 7.2 m and a = 2.2 m, respectively) and missions. This new design is expected to satisfy multiple CFETR operation modes of 0.2, 0.5, 1.0, and 1.5 GW fusion power and achieve tritium self-sufficiency. The feasibility of the updated blanket design is evaluated from the aspects of neutronics and thermo-hydraulics. Furthermore, the research and development (R&D) activities supporting to the WCCB blanket for CFETR are reported, including the design code, the water loop experiments, the pebble bed modeling and experiments, and the components fabrication technology. Keywords: Chinese fusion engineering testing, reactor, WCCB blanket, Research and development

Objective: Obesity is a complex chronic disease of high prevalence worldwide. Multiple factors play integral roles in obesity development, with rising interest focusing on the contribution of environmental pollutants frequent in modern society. Silver nanoparticles (AgNPs) are widely used for bactericidal purpose in various applications in daily life. However, their potential toxicity and contribution to the obesity epidemic are not clear. Methods: Beige adipocytes are newly discovered adipocytes characterized by high thermogenic and energy dissipating capacity upon activation and the “browning” process. In the present study, we assess the impact of AgNPs exposure on beige adipocytes differentiation and functionality both in vitro and in vivo. We also systematically investigate the influence of AgNPs on adiposity and metabolic performance in mice, as well as the possible underlying molecular mechanism. Results: The results showed that, independent of particle size, AgNPs inhibit the adipogenic, mitochondrial, and thermogenic gene programs of beige adipocytes, thus suppressing their differentiation ability, mitochondrial activity, and thermogenic response. Importantly, exposure to AgNPs in mice suppresses browning gene programs in subcutaneous fat, leading to decreased energy expenditure and increased adiposity in mice. Mechanistically, we found that AgNPs increase reactive oxidative species (ROS) levels and specifically activate MAPK-ERK signaling in beige adipocytes. The negative impacts of AgNPs on beige adipocytes can be ameliorated by antioxidant or ERK inhibitor FR180204 treatment. Conclusions: Taken together, these results revealed an unexpected role of AgNPs in promoting adiposity through the inhibition of beige adipocyte differentiation and functionality, possibly by disrupting ROS homeostasis and ERK phosphorylation. Future assessments on the health risk of AgNPs applications and their safe dosages are warranted. Keywords: Adiposity, Beige fat, Silver nanoparticles, Browning, Energy expenditure, Reactive oxidative species

The extracellular calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) play important roles in regulating calcium mobilization, calcium absorption, and calcium homeostasis, and they could be potential therapeutic targets to osteoporosis in laying hens. The present study investigated the molecular distribution of CaSR and VDR and the localization of CaSR in the kidney, proventriculus (true stomach), duodenum, jejunum, ileum, colon, cecum, shell gland, and tibia of laying hens at 3 different laying stages (19, 40, and 55 wk). The results showed that the relative mRNA abundance of CaSR in the kidney, ileum, proventriculus, duodenum, and colon was higher (P 0.05). The relative mRNA abundance of VDR was higher (P 0.05). The immunohistochemical results showed that the positive staining was found widely in each tissue. Moreover, different laying stages did not affect the localization of CaSR except for the tibia tissue. In conclusion, similar to VDR, CaSR was widely expressed not only in the gut but also in the tibia and shell gland in laying hens. The expression level of CaSR and VDR in all tested tissues was unchanged at the different laying stages.

Aim: To determine the associations between outdoor air pollution and hospital outpatient visits for mental disorders in China. Methods: We obtained data of 111,842 hospital outpatient visits for mental disorders from the largest hospitals of 13 cities, China, between January 01, 2013 and December 31, 2015. We collected air pollutant data including particulate matter ≤2.5 µm in diameter (PM2.5), particulate matter ≤10 µm in diameter (PM10), nitrogen dioxide (NO2), ozone (O3) and sulphur dioxide (SO2) from China National Environmental Monitoring Centre during the same period. We conducted a time-stratified case-crossover design with conditional logistic regression models to determine the associations. Results: A 10 µg/m3 increase in PM2.5, PM10, NO2 and SO2 was associated with a significant increase in hospital outpatient visits for mental disorders on the current day. When stratified by age, sex and season, the effects of PM2.5 and NO2 were robust among different subgroups at lag05 days. PM10 showed positive associations in males, in cold season, and in depression patients. SO2 showed positive associations in males, in cold season, and in anxiety patients. O3 showed positive associations in females, in warm season, and in depression patients. Nearly one sixth hospital outpatient visits for mental disorders can be attributable to NO2. Conclusions: Short-term increase in PM2.5, PM10, NO2, SO2 and O3 concentrations was significantly associated with exacerbation of mental disorders in China as indicated by increases in hospital outpatient visits. NO2 had more serious health threat than other pollutants in terms of mental disorders. Our findings strongly suggest a need for more strict emission control regulations to protect mental health from air pollution.

Summary: The partitioning of solar radiation in the Arctic sea ice during the melt season is investigated using a radiative transfer model containing three layers of melt pond, underlying sea ice, and ocean beneath ice. The wavelength distribution of the spectral solar irradiance clearly narrowed with increasing depth into ice, from 350–900 nm at the pond surface to 400–600 nm in the ocean beneath. In contrast, the net spectral irradiance is quite uniform. The absorbed solar energy is sensitive to both pond depth (Hp) and the underlying ice thickness (Hi). The solar energy absorbed by the melt pond (Ψp) is proportional only to Hp. However, the solar energy absorbed by the underlying ice (Ψi) is more complicated due to the counteracting effects arising from the pond and ice to the energy absorption. In September, Ψp decreased by 10% from its August value, which is attributed to more components in the shortwave band (

Background: IRX3 was recently reported as the effector of the FTO variants. We aimed to test IRX3's roles in the browning program and to evaluate the association between the genetic variants in IRX3 and human obesity. Methods: IRX3 expression was examined in beige adipocytes in human and mouse models, and further validated in induced beige adipocytes. The browning capacity of primary preadipocytes was assessed with IRX3 knockdown. Luciferase reporter analysis and ChIP assay were applied to investigate IRX3's effects on UCP1 transcriptional activity. Moreover, genetic analysis of IRX3 was performed in 861 young obese subjects and 916 controls. Results: IRX3 expression was induced in the browning process and was positively correlated with the browning markers. IRX3 knockdown remarkably inhibited UCP1 expression in induced mouse and human beige adipocytes, and also repressed the uncoupled oxygen consumption rate. Further, IRX3 directly bound to UCP1 promoter and increased its transcriptional activity. Moreover, 17 rare heterozygous missense/frameshift IRX3 variants were identified, with a significant enrichment in obese subjects (P = 0.038, OR = 2.27; 95% CI, 1.02–5.05). Conclusions: IRX3 deficiency repressed the browning program of white adipocytes partially by regulating UCP1 transcriptional activity. Rare variants of IRX3 were associated with human obesity.

As the development of sequencing technology, it is now possible to sequence individuals of each species. Although a number of different tools have been developed to detect individual variations, most of them cannot be run in parallel modes. To accelerate variation detection, PVCTools is introduced in this study. PVCTools splits the reference genome and alignment files into small pieces and runs them in parallel mode. Meanwhile, boundary noise is also considered in PVCTools. From the result of three different sets of test data, PVCTools performs much faster than most other current tools. At the same time, it keeps similar accuracy with other tools. PVCTools is free and open source software. The development of sequencing technology and growing sample numbers will make performance improvements such as PVCTools increasingly interesting.

Background: Tumor-derived exosomes are involved in tumor progression and immune invasion and might function as promising noninvasive approaches for clinical management. However, there are few reports on exosom-based markers for predicting the progression and adjuvant therapy response rate among patients with clear cell renal cell carcinoma (ccRCC). Methods: The signatures differentially expressed in exosomes from tumor and normal tissues from ccRCC patients were correspondingly deregulated in ccRCC tissues. We adopted a two-step strategy, including Lasso and bootstrapping, to construct a novel risk stratification system termed the TDERS (Tumor-Derived Exosome-Related Risk Score). During the testing and validation phases, we leveraged multiple external datasets containing over 2000 RCC cases from eight cohorts and one inhouse cohort to evaluate the accuracy of the TDERS. In addition, enrichment analysis, immune infiltration signatures, mutation landscape and therapy sensitivity between the high and low TDERS groups were compared. Finally, the impact of TDERS on the tumor microenvironment (TME) was also analysed in our single-cell datasets. Results: TDERS consisted of 12 mRNAs deregulated in both exosomes and tissues from patients with ccRCC. TDERS achieved satisfactory performance in both prognosis and immune checkpoint inhibitor (ICI) response across all ccRCC cohorts and other pathological types, since the average area under the curve (AUC) to predict 5-year overall survival (OS) was larger than 0.8 across the four cohorts. Patients in the TDERS high group were resistant to ICIs, while mercaptopurine might function as a promising agent for those patients. Patients with a high TDERS were characterized by coagulation and hypoxia, which induced hampered tumor antigen presentation and relative resistance to ICIs. In addition, single cells from 12 advanced samples validated this phenomenon since the interaction between dendritic cells and macrophages was limited. Finally, PLOD2, which is highly expressed in fibro- and epi‑tissue, could be a potential therapeutic target for ccRCC patients since inhibiting PLOD2 altered the malignant phenotype of ccRCC in vitro. Conclusion: As a novel, non-invasive, and repeatable monitoring tool, the TDERS could work as a robust risk stratification system for patients with ccRCC and precisely inform treatment decisions about ICI therapy.

Background: Emerging evidence suggests that cell deaths are involved in tumorigenesis and progression, which may be treated as a novel direction of cancers. Recently, a novel type of programmed cell death, disulfidptosis, was discovered. However, the detailed biological and clinical impact of disulfidptosis and related regulators remains largely unknown. Methods: In this work, we first enrolled pancancer datasets and performed multi-omics analysis, including gene expression, DNA methylation, copy number variation and single nucleic variation profiles. Then we deciphered the biological implication of disulfidptosis in clear cell renal cell carcinoma (ccRCC) by machine learning. Finally, a novel agent targeting at disulfidptosis in ccRCC was identified and verified. Results: We found that disulfidptosis regulators were dysregulated among cancers, which could be explained by aberrant DNA methylation and genomic mutation events. Disulfidptosis scores were depressed among cancers and negatively correlated with epithelial mesenchymal transition. Disulfidptosis regulators could satisfactorily stratify risk subgroups in ccRCC, and a novel subtype, DCS3, owning with disulfidptosis depression, insensitivity to immune therapy and aberrant genome instability were identified and verified. Moreover, treating DCS3 with NU1025 could significantly inhibit ccRCC malignancy. Conclusion: This work provided a better understanding of disulfidptosis in cancers and new insights into individual management based on disulfidptosis.

Litopenaeus vannamei is the most economically important aquaculture shrimp species, and feeding normal feeds cannot ripen the ovaries of female shrimp during the farming process. In production practice, eyestalk ablation (ESA) in combination with the feeding of fresh baits is widely used to accelerate ovarian maturation. However, this method is considered cruel and results in some issues such as reduced parental immunity and low egg quality. Recently, we found that ovary maturation can also be rapidly induced by using only fresh baits, but the mechanism behind this is still unclear. In this study, we integrated the results of histological assays, biochemical analysis, ovarian transcriptome and intestinal microbiota to reveal that fresh baits can promote ovarian maturation by modulating ovarian and hepatopancreatic lipid metabolism, promoting vitamin K metabolism, the tricarboxylic acid cycle, and the proliferation of beneficial bacteria, as well as increasing vitamin B metabolism in the ovary. The present study is of great significance for the development of functional compound feeds for parent shrimps and for developing non-ESA methods for artificial gonad ripening of shrimps.

Arsenic (As) is a widespread metalloid and human carcinogen found in the natural environment, and multiple toxic effects have been shown to be associated with As exposure. As can be accumulated in the spleen, the largest peripheral lymphatic organ, and long-term exposure to As can lead to splenic injury. In this study, a Sprague-Dawley (SD) rat model of As-poisoned was established, aiming to explore the molecular mechanism of As-induced immune injury through the combined analysis of proteomics and metabolomics of rats’ spleen. After feeding the rats with As diet (50 mg/kg) for 90 days, the spleen tissue of the rats in the As-poisoned group was damaged, the level of As was significantly higher than that of the control group (P < 0.001), and the level of inflammatory cytokine interleukin-6 (IL-6) was decreased (P < 0.01). Proteomics and metabolomics results showed that a total of 134 differentially expressed proteins (DEPs) (P < 0.05 and fold change > 1.2) and 182 differentially expressed metabolites (DEMs) (VIP >1 and P < 0.05) were identified in the spleens of the As poisoned group compared to the control group (As/Ctrl). The proteomic results highlight the role of hypoxia-inducible factors (HIF), natural killer cell mediated cytotoxicity, and ribosomes. The major pathways of metabolic disruption included arachidonic acid (AA) metabolism, glycerophospholipid metabolism and folate single-carbon pool. The integrated analysis of these two omics suggested that Hmox1, Stat3, arachidonic acid, phosphatidylcholine and leukotriene B4 may play key roles in the mechanism of immune injury to the spleen by As exposure. The results indicate that As exposure can cause spleen damage in rats. Through proteomic and metabolomic analysis, the key proteins and metabolites and their associated mechanisms were obtained, which provided a basis for further understanding of the molecular mechanism of spleen immune damage caused by As exposure.