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Yilun Lu,1– 3,* Ding Li,1– 3,* Yueyue Huang,1– 3 Yuanyuan Sun,1– 3 Hongmin Zhou,1– 3 Fanrong Ye,1– 3 Hongjing Yang,1– 3 Tingting Xu,1– 3 Shichao Quan,3– 6 Jingye Pan1– 5 1Department of Intensive Care Unit, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, Wenzhou, People’s Republic of China; 3Wenzhou Key Laboratory of Critical Care and Artificial Intelligence, Wenzhou, People’s Republic of China; 4Collaborative Innovation Center for Intelligence Medical Education, Wenzhou, People’s Republic of China; 5Zhejiang Engineering Research Center for Hospital Emergency and Process Digitization, Wenzhou, People’s Republic of China; 6Department of General Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingye Pan, Department of Intensive Care Unit, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Email wmupanjingye@126.com Shichao Quan, Department of General Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Email generalpractice@qq.comPurpose: Sepsis is an aggressive and life-threatening organ dysfunction induced by infection. Excessive inflammation and coagulation contribute to the negative outcomes for sepsis, resulting in high morbidity and mortality. In this study, we explored whether Eupatilin could alleviate lung injury, reduce inflammation and coagulation during sepsis.Methods: We constructed an in vitro sepsis model by stimulating RAW264.7 cells with 1 μg/mL lipopolysaccharide (LPS) for 6 hours. The cells were divided into control group, LPS group, LPS+ Eupatilin (Eup) group, and Eup group to detect their cell activity and inflammatory cytokines and coagulation factor levels. Cells in LPS+Eup and Eup group were pretreated with Eupatilin (10μM) for 2 hours. In vivo, mice were divided into sham operation group, cecal ligation and puncture (CLP) group and Eup group. Mice in the CLP and Eup groups were pretreated with Eupatilin (10mg/kg) for 2 hours by gavage. Lung tissue and plasma were collected and inflammatory cytokines, coagulation factors and signaling were measured.Results: In vitro, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and tissue factor (TF) expression in LPS-stimulated RAW264.7 cells was downregulated by Eupatilin (10μM). Furthermore, Eupatilin inhibited phosphorylation of the JAK2/STAT3 signaling pathway and suppressed p-STAT3 nuclear translocation. In vivo, Eupatilin increased the survival rate of the mice. In septic mice, plasma concentrations of TNF-α, IL-1β and IL-6, as well as TF, plasminogen activator inhibitor 1 (PAI-1), D-dimer, thrombin-antithrombin complex (TAT) and fibrinogen were improved by Eupatilin. Moreover, Eupatilin alleviated lung injury by improving the expression of inflammatory cytokines and TF, fibrin deposition and macrophage infiltration in lung tissue.Conclusion: Our results revealed that Eupatilin may modulate inflammation and coagulation indicators as well as improve lung injury in sepsis via the JAK2/STAT3 signaling pathway.Keywords: Eupatilin, sepsis, inflammation, coagulation, JAK2/STAT3

Jiawei Lv,1 Kai Zhuang,1 Xiyu Jiang,1 Heqing Huang,1,2 Shijian Quan1 1Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, People’s Republic of China; 2Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, People’s Republic of ChinaCorrespondence: Heqing Huang; Shijian QuanDepartment of Pharmacology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, No. 232 East Wai Huan Road, Guangzhou 510006, People’s Republic of ChinaTel +86 1 392 211 9719Email huangheq@mail.sysu.edu.cn; quansj@gzucm.edu.cnPurpose: Glomerular sclerosis and renal interstitial fibrosis are the most important pathologies in the development of kidney damage under diabetic conditions. Smad3 plays antagonistic roles in high glucose-induced renal tubular fibrosis, which is an important treatment target for diabetic nephropathy (DN). Formononetin (FMN) has multiple effects on diabetic vascular complications including DN. However, whether it plays an anti-fibrosis role by regulating smad3 is unclear. The purpose of this study was to evaluate the renoprotective effect of FMN by suppressing smad3 expression in db/db mice.Methods: FMN was orally administered to db/db mice with a dose of 25 or 50 mg/kg/day for 8 weeks. At the end of the study, serum, urine, and kidney samples were collected for biochemical and pathological examinations. The expressions of proteins and mRNA associated with renal fibrosis were determined by biochemical, histological, immunofluorescence, and real-time PCR analysis.Results: The results showed that FMN substantially improved the glucolipid metabolism, reduced the oxidative stress, and protected renal function in db/db mice. Meanwhile, protein and mRNA expression of smad3 and related regulatory factor of extracellular matrix deposition were significantly suppressed.Conclusion: The present study suggested that FMN has a good renoprotective effect in DN, which plays an anti-fibrosis role in db/db mice by suppressing the expression of smad3.Keywords: formononetin, diabetic nephropathy, db/db mice, renal fibrosis, expression of smad3, antioxidants

Jia Mi,1,* Wenda He,1,* Jiawei Lv,1 Kai Zhuang,1 Heqing Huang,1,2 Shijian Quan1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heqing Huang; Shijian QuanDepartment of School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, No. 232 East Wai Huan Road, Guangzhou 510006, People’s Republic of ChinaTel +86 1 392 211 9719Email Huangheq@mail.sysu.edu.cn quansj@gzucm.edu.cnPurpose: Activation of the hypothalamus-pituitary-adrenal (HPA) axis pathway is closely related to insulin resistance (IR), glucose, and lipid metabolism disorders in type 2 diabetes mellitus (T2DM). Berberine (BBR) has effect on regulating disorder of glucose and lipid metabolism in T2DM. In fact, activation of the HPA axis pathway is closely related to IR, glucose, and lipid metabolism disorders in T2DM. Here, we investigated whether the therapeutic effect of BBR on T2DM rats is acted through the HPA axis pathway. Methods: In this research, we investigated the effects of BBR on the HPA-axis pathway-related indicators and expression of skeletal muscle glucose transporter 4 (GLUT4) in the high-fat diet and streptozotocin-induced T2DM rats, and identify its possible mechanism of improving IR in T2DM.Results: BBR significantly reduced fasting blood glucose, total cholesterol, and low-density lipoprotein cholesterol in model rats. It also improved the abnormalities of the high-density lipoprotein cholesterol, the insulin resistance index, the insulin sensitivity index, glucagon, and insulin levels. BBR decreased levels of hypothalamic Orexin-A, the OX2R receptor, the corticotropin-releasing hormone, the pituitary and the plasma adrenocorticotropic hormone, as well as serum and urine corticosterone. At the same time, BBR increased mRNA and protein expressions of GLUT4 in skeletal muscles of model rats as well.Conclusion: Those results suggested that BBR can exert inhibition on the HPA-axis and increased skeletal muscle expression of GLUT4 proteins, which may be one of the important mechanisms in BBR to improve IR and regulating glucose and lipid metabolism in T2DM rats.Keywords: berberine, type 2 diabetes mellitus, insulin resistance, the HPA-axis, GLUT4

Abstract Background Cellular carcinogenesis is often marked by the accumulation of lipid droplets (LDs) due to reprogrammed lipid metabolism. LDs are dynamic organelles that primarily store intracellular triacylglycerol (TAG) and cholesteryl esters (CEs). Transmembrane protein 68 (TMEM68), a potential modifier of human breast cancer risk and outcomes, functions as a diacylglycerol acyltransferase, synthesizing TAG. However, the specific roles of TMEM68 in breast cancer cells remain unclear. Methods Gene expression profiling interactive analysis and survival analysis were conducted. TMEM68 was overexpressed or knockdown in breast cancer cells to assess its impact on cell proliferation, migration and invasion. Targeted quantitative lipidomic analysis and quantitative polymerase chain reaction were used to profile lipid alterations and examine gene expression related to lipid metabolism following changes in TMEM68 levels. Results TMEM68 gene was upregulated in breast cancer patients and higher TMEM68 levels were associated with poorer survival outcomes. Overexpression of TMEM68 increased breast cancer cell proliferation and invasion, whereas knockdown had minimal or no impact on reducing proliferation and invasion. Altering TMEM68 levels resulted in corresponding changes in TAG levels and cytoplasmic LDs, with overexpression increasing both and knockdown decreasing them. Lipidomic analysis revealed that TMEM68 regulated TAG levels and altered diacylglycerol content in breast cancer cells. Additionally, TMEM68 influenced the metabolism of glycerophospholipids, CEs and acylcarnitines. TMEM68 also modified the expression of key genes encoding enzymes related to neutral lipid metabolism, including TAG and CEs. Conclusions TMEM68 is highly expressed in breast cancer and negatively correlated with survival. Its overexpression promotes breast cancer cell proliferation while knockdown has varied effects depending on TMEM68 levels. TMEM68 regulates intracellular TAG and LDs contents along with alterations in glycerophospholipids. These findings suggest that TMEM68 may drive breast cancer cells proliferation by modulating TAG and LD content.

Recent studies have confirmed that melatonin and N6-methyladenosine (m6A) modification can influence bone cell differentiation and bone formation. Melatonin can also regulate a variety of biological processes through m6A modification. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) serves as a reader of m6A modification. In this study, we used the hindlimb unloading model as an animal model of bone loss induced by simulated microgravity and used 2D clinorotation to simulate a microgravity environment for cells on the ground. We found that hnRNPA2B1 was downregulated both in vitro and in vivo during simulated microgravity. Further investigations showed that hnRNPA2B1 could promote osteoblast differentiation and that overexpression of hnRNPA2B1 attenuated the suppression of osteoblast differentiation induced by simulated microgravity. We also discovered that melatonin could promote the expression of hnRNPA2B1 under simulated microgravity. Moreover, we found that promotion of osteoblast differentiation by melatonin was partially dependent on hnRNPA2B1. Therefore, this research revealed, for the first time, the role of the melatonin/hnRNPA2B1 axis in osteoblast differentiation under simulated microgravity. Targeting this axis may be a potential protective strategy against microgravity-induced bone loss and osteoporosis.

Abstract Background Machine learning (ML) is extensively employed for forecasting the outcome of various illnesses. The objective of the study was to develop ML based classifiers using a stacking ensemble strategy to predict the Japanese Orthopedic Association (JOA) recovery rate for patients with degenerative cervical myelopathy (DCM). Methods A total of 672 patients with DCM were included in the study and labeled with JOA recovery rate by 1-year follow-up. All data were collected during 2012–2023 and were randomly divided into training and testing (8:2) sub-datasets. A total of 91 initial ML classifiers were developed, and the top 3 initial classifiers with the best performance were further stacked into an ensemble classifier with a supported vector machine (SVM) classifier. The area under the curve (AUC) was the main indicator to assess the prediction performance of all classifiers. The primary predicted outcome was the JOA recovery rate. Results By applying an ensemble learning strategy (e.g., stacking), the accuracy of the ML classifier improved following combining three widely used ML models (e.g., RFE-SVM, EmbeddingLR-LR, and RFE-AdaBoost). Decision curve analysis showed the merits of the ensemble classifiers, as the curves of the top 3 initial classifiers varied a lot in predicting JOA recovery rate in DCM patients. Conclusions The ensemble classifiers successfully predict the JOA recovery rate in DCM patients, which showed a high potential for assisting physicians in managing DCM patients and making full use of medical resources.

Abstract The Qinghai-Tibet Plateau (QTP), renowned for its exceptional biological diversity, is home to numerous endemic species. However, research on the virology of vulnerable vertebrates like yaks remains limited. In this study, our objective was to use metagenomics to provide a comprehensive understanding of the diversity and evolution of the gut virome in yak populations across different regions of the QTP. Our findings revealed a remarkably diverse array of viruses in the gut of yaks, including those associated with vertebrates and bacteriophages. Notably, some vertebrate-associated viruses, such as astrovirus and picornavirus, showed significant sequence identity across diverse yak populations. Additionally, we observed differences in the functional profiles of genes carried by the yak gut virome across different regions. Moreover, the virus-bacterium symbiotic network that we discovered holds potential significance in maintaining the health of yaks. Overall, this research expands our understanding of the viral communities in the gut of yaks and highlights the importance of further investigating the interactions between viruses and their hosts. These data will be beneficial for revealing the crucial role that viruses play in the yak gut ecology in future studies.

Abstract Background Mechanical unloading-induced bone loss threatens prolonged spaceflight and human health. Recent studies have confirmed that osteoporosis is associated with a significant reduction in bone microvessels, but the relationship between them and the underlying mechanism under mechanical unloading are still unclear. Methods We established a 2D clinostat and hindlimb-unloaded (HLU) mouse model to simulate unloading in vitro and in vivo. Micro-CT scanning was performed to assess changes in the bone microstructure and mass of the tibia. The levels of CD31, Endomucin (EMCN) and histone deacetylase 6 (HDAC6) in tibial microvessels were detected by immunofluorescence (IF) staining. In addition, we established a coculture system of microvascular endothelial cells (MVECs) and osteoblasts, and qRT‒PCR or western blotting was used to detect RNA and protein expression; cell proliferation was detected by CCK‒8 and EdU assays. ChIP was used to detect whether HDAC6 binds to the miRNA promoter region. Results Bone mass and bone microvessels were simultaneously significantly reduced in HLU mice. Furthermore, MVECs effectively promoted the proliferation and differentiation of osteoblasts under coculture conditions in vitro. Mechanistically, we found that the HDAC6 content was significantly reduced in the bone microvessels of HLU mice and that HDAC6 inhibited the expression of miR-375-3p by reducing histone acetylation in the miR-375 promoter region in MVECs. miR-375-3p was upregulated under unloading and it could inhibit MVEC proliferation by directly targeting low-density lipoprotein-related receptor 5 (LRP5) expression. In addition, silencing HDAC6 promoted the miR-375-3p/LRP5 pathway to suppress MVEC proliferation under mechanical unloading, and regulation of HDAC6/miR-375-3p axis in MVECs could affect osteoblast proliferation under coculture conditions. Conclusion Our study revealed that disuse-induced bone loss may be closely related to a reduction in the number of bone microvessels and that the modulation of MVEC function could improve bone loss induced by unloading. Mechanistically, the HDAC6/miR-375-3p/LRP5 pathway in MVECs might be a promising strategy for the clinical treatment of unloading-induced bone loss.

In this work, homogeneous surface oxidation of hafnium disulfide (HfS2) is achieved by an extremely simple thermal treatment, i.e., mild oxidization in air. Due to the high thermal stability of hafnium dioxide (HfO2), atomically flat HfO2 is formed on top of unoxidized HfS2 and unlimited layer-by-layer oxidation is observed. The thickness of HfO2 can be controlled by oxidation temperature and time. The HfO2 layer fabricated by the oxidation of HfS2 is smooth and atomically flat with roughness comparable to that of pristine HfS2. Growth of a high-quality, uniform, atomically flat oxide film on top of semiconductor is the first step for the fabrication of field effect transistors and metal-insulator-semiconductor devices. Thus, our results will facilitate the future fabrication of HfO2 films with atomic-scale thickness. [ABSTRACT FROM AUTHOR]

Abstract Myocardial infarction (MI) has a 5-year mortality rate of more than 50% due to the lack of effective treatments. Interactions between cardiomyocytes and the MI microenvironment (MIM) can determine the progression and fate of infarcted myocardial tissue. Here, a specially designed Melanin-based composite nanomedicines (MCN) is developed to effectively treat MI by reprogramming the MIM. MCN is a nanocomposite composed of polydopamine (P), Prussian blue (PB) and cerium oxide (CexOy) with a Mayuan-like structure, which reprogramming the MIM by the efficient conversion of detrimental substances (H+, reactive oxygen species, and hypoxia) into beneficial status (O2 and H2O). In coronary artery ligation and ischemia reperfusion models of male mice, intravenously injecting MCN specifically targets the damaged area, resulting in restoration of cardiac function. With its promising therapeutic effects, MCN constitutes a new agent for MI treatment and demonstrates potential for clinical application.

Parameters of foam penetration in earth pressure balance (EPB) shield tunnelling, such as permeability coefficients and penetration distances, significantly impact tunnel face stability. However, existing studies have faced inaccuracies in analysing these parameters due to imitations in experimental methods. This study addresses this issue by employing enhanced methods for a more precise analysis of foam penetration. Experiments involving three distinct sand types (coarse, medium, and fine) and three foam expansion ratios (FER) (10, 15, and 20) are conducted using a modified model test setup. Benefiting from a novel computer vision-based method, the model test outcomes unveil two distinct foam penetration paths: liquid migration (Lw) and bubble migration (Lf). Three penetration phases — namely, injection, blockage & drainage, and breakage — are identified based on Lw and Lf variations. The initial “injection” phase conforms to Darcy's law and is amenable to mathematical description. The foam with FER of 15 has the maximum viscosity and, hence the Lf and permeability in the penetration tests with FER of 15 are the lowest in the same sand. The bubble size distribution of foam with different FER shows minor differences. Nevertheless, the characteristics of foam penetration vary due to the distinct particle size distribution (PSD) of different sands. Foam penetration creates low-permeability layers in both medium and fine sands due to the larger bubble size of the foam compared to the estimated pore sizes of medium and fine sands. While the coarse sand results in a different situation due to its large pore size. The distinctive characteristics of foam penetration in different sand strata are notably shaped by FER, PSD, and pore size distributions. These insights shed light on the complex interactions during foam penetration at the tunnel face, contributing valuable knowledge to EPB shield tunnelling practices.

Abstract Background The glandular trichomes of tobacco (Nicotiana tabacum) can efficiently produce secondary metabolites. They act as natural bioreactors, and their natural products function to protect plants against insect-pests and pathogens and are also components of industrial chemicals. To clarify the molecular mechanisms of tobacco glandular trichome development and secondary metabolic regulation, glandular trichomes and glandless trichomes, as well as other different developmental tissues, were used for RNA sequencing and analysis. Results By comparing glandless and glandular trichomes with other tissues, we obtained differentially expressed genes. They were obviously enriched in KEGG pathways, such as cutin, suberine, and wax biosynthesis, flavonoid and isoflavonoid biosynthesis, terpenoid biosynthesis, and plant–pathogen interaction. In particular, the expression levels of genes related to the terpenoid, flavonoid, and wax biosynthesis pathway mainly showed down-regulation in glandless trichomes, implying that they lack the capability to synthesize certain exudate compounds. Among the differentially expressed genes, 234 transcription factors were found, including AP2-ERFs, MYBs, bHLHs, WRKYs, Homeoboxes (HD-ZIP), and C2H2-ZFs. These transcription factor and genes that highly expressed in trichomes or specially expressed in GT or GLT. Following the overexpression of R2R3-MYB transcription factor Nitab4.5_0011760g0030.1 in tobacco, an increase in the number of branched glandular trichomes was observed. Conclusions Our data provide comprehensive gene expression information at the transcriptional level and an understanding of the regulatory pathways involved in glandular trichome development and secondary metabolism.

The recycling of graphite from spent lithium-ion batteries (LIBs) is overlooked due to its relatively low added value and the lack of efficient recovering methods. To reuse the spent graphite anodes, we need to eliminate their useless components (mainly the degraded solid electrolyte interphase, SEI) and reconstruct their damaged structure. Herein, a facile and efficient strategy is proposed to recycle the spent graphite on the basis of the careful investigation of the composition of the cycled graphite anodes and the rational design of the regeneration processes. The regenerated graphite, which is revitalized by calcination treatment and acid leaching, delivers superb rate performance and a high specific capacity of 370 mAh g−1 (∼99% of its theoretical capacity) after 100 cycles at 0.1 C, superior to the commercial graphite anodes. The improved electrochemical performance could be attributed to unchoked Li+ transport channels and enhanced charge transfer reaction due to the effective destruction of the degraded SEI and the full recovery of the damaged structure of the spent graphite. This work clarifies that the electrochemical performance of the regenerated graphite could be deteriorated by even a trace amount of the residual “impurity” and provides a facile method for the efficient regeneration of graphite anodes.

Porcine deltacoronavirus (PDCoV), a newly discovered intestinal coronavirus, has rapidly spread among pigs worldwide and has shown the potential for cross-species infection. However, the interaction mechanism between PDCoV and the host’s antiviral response is still poorly understood. In this study, an E3 ubiquitin ligase FBXW8 was explored on PDCoV proliferation. Our findings demonstrate that PDCoV infection increases the expression of FBXW8 through p65-mediated activation of its promoter. We also discovered that FBXW8 suppresses PDCoV replication by directly targeting and inducing the degradation of the PDCoV-encoded nucleocapsid (N) protein. Interestingly, FBXW8 catalyzes the K48-linked polyubiquitination of the PDCoV N protein at a unique lysine-rich region (KR). Furthermore, we observed that the FBXW8-ubiquitinated PDCoV N protein interacts with NDP52, a cargo receptor, leading to autophagic degradation instead of proteasomal degradation. In summary, these findings reveal FBXW8 as a novel host antiviral factor involved in PDCoV infection. It mediates the NDP52-dependent autophagic degradation of the PDCoV N protein. These results provide new insights and a potential target for host defenses against PDCoV.

BackgroundTumor antigen peptide vaccines have shown remarkable efficacy, safety, and reliability in recent studies. However, the screening process for immunopotent antigenic peptides is cumbersome, limiting their widespread application. Identifying neoantigen peptides that can effectively trigger an immune response is crucial for personalized cancer treatment.MethodsWhole exome sequencing was performed on patient-derived colon cancer cells to predict 9-amino-acid (9aa) neoantigen peptides. In vitro simulation of endogenous antigen presentation by antigen-presenting cells (dendritic cells) to CD8+ T cells was conducted, aiming to activate the CD8+ immune response to the predicted antigens. The immunological effects of each neoantigen were assessed using flow cytometry and ELISpot assays, while the relationship between neoantigen immunogenicity and MHC molecular affinity was examined.Results1. Next-generation sequencing (NGS) predicted 9-amino acid (9aa) neoantigen peptides for subsequent immunological analysis.2. Higher mDC Levels in Experimental Group: CD11c+CD83+ mature dendritic cells (mDCs) were 96.6% in the experimental group, compared to 0.051% in the control group. CD80 fluorescence intensity was also significantly higher in the experimental group, confirming a greater mDC presence.3. Neoantigen Peptides Promote CD4+, CD8+ T, and NK Cell Proliferation: After 14 days, flow cytometry showed higher percentages of CD4+ T (37.41% vs 7.8%), CD8+ T (16.67% vs 14.63%), and NK cells (33.09% vs 7.81%) in the experimental group, indicating that the neoantigen peptides induced proliferation of CD4+, CD8+ T cells, and NK cells. 4. The results, analyzed using two-way ANOVA, showed that the standardized T-value for HLA molecular affinity variation in the 1-4 range (Group B) was significantly higher than for ≤1 (Group A, p < 0.0001) and >4 (Group C, p < 0.05). Regarding HLA-allele genotypes, HLA-Type 1 had a significantly higher standardized T-value than HLA-Type 2 (p < 0.05) and HLA-Type 3 (p < 0.0001). HLA-Type 1 was identified as the allele associated with the highest T-value.Conclusion1. The most immunogenic neoantigens typically exhibit an MHC molecular affinity variation between 1 and 4, indicating that stronger immunogenicity correlates with higher MHC molecular affinity variation. 2. Each patient's HLA molecules were classified into Types 1, 2, and 3, with Type 1 showing the highest binding capacity for neoantigens. Our findings indicate that the most immunogenic neoantigens were associated with HLA Type 1. 3. Neoantigen peptides were shown to activate the proliferation of both CD8+ T-cells and induce proliferation of CD4+ T-cells and NK cells. 4. Variation in MHC molecular affinity and HLA neoantigen genotype are anticipated to serve as valuable variables for screening highly immunogenic neoantigens, facilitating more efficient preparation of effective polypeptide tumor vaccines.

IntroductionThe bar-headed goose is a typical high-altitude bird that primarily inhabits alpine lakes and wetlands in Central Asia, with a remarkable ability to adapt to high elevations. Previous studies have shown that they can be infected with parasites such as Cryptosporidium spp. At present, there were few reports on its infection with the virus.MethodsIn this study, we utilized viral metagenomics to conduct a detailed analysis of the viral components in the fecal samples of bar-headed geese (Anser indicus) from the Tibet region of China.ResultsMultiple novel viruses were identified including four novel astroviruses, four novel caliciviruses, ten novel circoviruses, and nineteen novel parvoviruses. Among them, four astroviruses shared the highest amino acid sequence identities of 63.45–99.47% with different avastrovirus strains. Four caliciviruses and ten circoviruses were identified as unclassified caliciviruses and unclassified circoviruses, separately. Nineteen parvoviruses clustering into four groups maybe four different novel species of the genus Chaphamaparvovirus.ConclusionThese newly discovered viruses have potential implications for the health of avian species, particularly bar-headed geese. This study not only helps us understand the health status of bar-headed geese, but also offers crucial genomic information for future disease prevention and treatment strategies.

Cold stress is a critical factor affecting rice production worldwide. The application of cold-resistant agents may improve the cold resistance and yield of crops. To screen for suitable cold-resistant agents for machine-transplanted early rice, the effects of uniconazole, abscisic acid, and zinc-amino acids chelate and their spraying times (seed soaking stage, one leaf and one heart stage, two leaves and one heart stage, 7 days before the transplanting stage, and regreening stage) on the yield and cold resistance of machine-transplanted early rice were investigated. Moreover, the application method (spraying amount: 750 and 1125 g ha−1; spraying time: 7 days before the transplanting stage, transplanting stage, regreening stage, and transplanting stage and regreening stage) for the most suitable cold-resistant agent was optimized. The zinc-amino acids chelate was better than the other two cold-resistant agents for promoting rice tillering and increasing the leaf area index, dry matter weight, antioxidant enzyme activities (CAT, SOD, POD) and yield (i.e., 9.22% and 7.14% higher than uniconazole and abscisic acid, respectively), especially when it was applied in the regreening stage. The examination of spraying amounts and times indicated that the zinc-amino acids chelate dosage had no significant effect on the yield and cold resistance of early rice. However, the rice yield and antioxidant enzyme activities were highest when samples were sprayed once in the transplanting stage and the regreening stage. On the basis of the study results, 750 g ha−1 zinc-amino acids chelate applications in the transplanting and regreening stages of machine-transplanted early rice plants may be ideal for increasing cold stress resistance and yield.

The viral metagenomics approach is an effective technique for investigating and analysing both existing and emerging viruses in humans and diverse animal samples. The ruddy shelduck, a nationally protected secondary key species of wild animals, has become the predominant species among overwintering waterbirds in Qinghai Lake. Viruses carried by ruddy shelducks can potentially infect humans or other animals; however, limited research on the faecal virome of ruddy shelducks is currently available. In the present study, faecal samples of ruddy shelducks collected from Saga County, Shigatse City, Tibet, China, were subjected to viral metagenomic analysis. The predominant viral families identified in ruddy shelduck samples were Picornaviridae, Parvoviridae, Microviridae, Vilyaviridae, Astroviridae, and Caliciviridae. Among these, two picornavirus genomes have been identified as new strains of the genus Megrivirus in the family Parvoviridae. In addition, viruses that infect parasites and bacteria have been identified and characterised. The present study enhances our comprehension of the composition of the viral community in ruddy shelducks faeces and highlights the dynamic nature of viral evolution and the significance of continuous monitoring to assess potential risks to wildlife and public health.

The elusive factors determining peroxymonosulfate (PMS) activation lead to the “trial-and-error” method when developing efficient catalysts. Herein, we demonstrate that the suitable bonding pattern between PMS and exposed facets of CuO is the key parameter in catalysis. The kobs of ibuprofen removal by CuO with (110) facet (p-CuO) was 1.67 times higher than that of CuO with (001) facet (c-CuO). Simultaneously, Cu(III) was confirmed to be the primary intermediate oxidant among multiple reactive species (Cu(III), •OH, and 1O2 in both CuO/PMS systems, whereas O2•− only in c-CuO/PMS system). Furthermore, density functional theory calculations unveiled that compared to chaise longue connection between p-CuO and PMS, the higher adsorption energy (Eads) of bridge-like connection between c-CuO and PMS leads to a more stable intermediate (−5.56 eV vs −3.76 eV), thus hindering the formation of Cu(III). This work provides new opportunities for fabricating diverse metal oxides with new interfaces as PMS catalysts.

In this paper, solution soaking is used to deposit Rhodamine 6G (R6G+) dye molecules on two-dimensional materials, i.e., graphene and molybdenum disulfide (MoS2), which concentrate the solution-phase R6G+ molecules into a solid thin film. The concentration of adsorbed molecules on graphene/MoS2 can be calculated using graphene 2D/MoS2 A1g peak as an internal standard. It is found that optical imaging also provides a quantitative way to determine the concentration of adsorbed molecules whose results are further confirmed by atomic force microscopy. The obtained results will facilitate the fabrication of surface-enhanced Raman scattering substrates using two-dimensional materials. Adsorptive removal of various dyes to lighten effluent pollution from industries is a basic and applied research area. Carbon-based materials are well-known adsorbents for dyes. Using optical imaging, the dynamic processes of solution-dependent R6G+ sorption and desorption onto graphene are monitored. Our results also shed light on potentially using graphene materials as adsorbents for toxic and carcinogenic molecules. [ABSTRACT FROM AUTHOR]

Abstract Optimizing thermoelectric conversion efficiency requires the compromise of electrical and thermal properties of materials, which are hard to simultaneously improve due to the strong coupling of carrier and phonon transport. Herein, a one-pot approach realizing simultaneous second phase and Cu vacancies modulation is proposed, which is effective in synergistically optimizing thermoelectric performance in copper sulfides. Multiple lattice defects, including nanoprecipitates, dislocations, and nanopores are produced by adding a refined ratio of Sn and Se. Phonon transport is significantly suppressed by multiple mechanisms. An ultralow lattice thermal conductivity is therefore obtained. Furthermore, extra Se is added in the copper sulfide for optimizing electrical transport properties by inducing generating Cu vacancies. Ultimately, an excellent figure of merit of ~1.6 at 873 K is realized in the Cu1.992SSe0.016(Cu2SnSe4)0.004 bulk sample. The simple strategy of inducing compositional and structural modulation for improving thermoelectric parameters promotes low-cost high-performance copper sulfides as alternatives in thermoelectric applications.

To address the limited wear resistance attributed to the insufficient initial mechanical properties observed in high manganese steel (HM) wear behavior, we introduced nitrogen (N) to modulate precipitation behavior, thereby elevating material mechanical properties and wear resistance, and this was further enhanced through aging treatments. Due to the nitrogen addition, the precipitates transformed from MC to M(C, N), concurrently triggering a substantial increase and refinement in precipitates. As a result, nitrogenous high manganese steel (NHM) exhibited improved strength, toughness, and work-hardening capacity. The enhancements amounted to 67–77 MPa in yield strength and 5.3–9.3 % in elongation, with these improvements becoming more pronounced after extending the aging treatment. Under impact abrasive wear conditions, the NHM demonstrated the development of a stable work-hardened layer. The NHM hardened layer rapidly reached a depth of 4–6 mm, effectively resisting abrasive embedding and suppressing matrix abrasion. This transitioned the primary wear mechanisms from cutting and plowing to plastic deformation and micro-spalling. Additionally, NHM's great uniformity and toughness-plasticity played a crucial role in preventing the initiation and propagation of fatigue cracks and fatigue sheds.

Particulate matter (PM) has always received widespread attention, PM2.5 pollution is associated with many adverse effects, including cardiovascular, respiratory and metabolic diseases and mood disorders. However, the underlying mechanisms are not yet clear. In this study, the small animal whole body inhalation exposure system collected real-time PM2.5 in the real environment, which can truly reflect the presence status of PM2.5 in the atmospheric environment. This study investigated the depressive like behavior of mice exposed to PM2.5 for a long time and proved its molecular mechanism through RNA-seq. C57BL/6 male mice were exposed to ambient air together with control mice, who breathed air filtered through high-efficiency air particulate filters. Depression like behavior was observed in mice exposed to PM for 4, 6, and 8 weeks through behavioral experiments, EEG signals, and pathological sections. RNA-seq results indicated that the depressive like behavior of mice exposed to PM2.5 might be related to pro-inflammatory and anti-inflammatory cytokines, as well as the BDNF pathways in the hippocampus and olfactory bulb. This study suggests that PM2.5 may induce depression in mice through the MAPK/CREB/BDNF pathway. Environmental Implication: Atmospheric particulate matter has been classified as Class 1 pollutant by the International Agency for Research on Cancer. Current research mainly believed that PM2.5 seriously affected lung health, but there was little research on the effects of PM2.5 on other organs. With the improvement of quality of life, people were paying more attention to mental health, while there is little research on the effects of PM2.5 on brain. This study simulated a real PM2.5 exposure environment and explored the effects of PM2.5 on the brain of mice, provided a solid scientific basis for inducing depression after PM2.5 exposure.

Abstract. Introduction:. Central neuropathic pain (CNP) commonly develops in patients after spinal cord injury (SCI), causing debilitating symptoms and sensory abnormalities to mechanical and thermal stimuli. The biological variability of pain phenotypes in individuals has limited the number of positive outcomes. Thus, it is necessary to investigate the physiological processes contributing to sensory changes that develop over time. Objective:. To investigate the physiological processes contributing to neuropathic pain sensory changes and locomotor impairments with sensory phenotypes that develop over time. Methods:. Using the tail flick and von Frey tests, we performed hierarchical clustering to determine the subpopulation of rats that developed thermal and mechanical sensory abnormalities. To measure inflammation as a potential mediator of CNP phenotypes, we used flow cytometry and immunohistochemistry. Finally, to assess the secondary effects on locomotor recovery, up to 8 weeks after injury, we used the CatWalk test to assess multiple parameters of gait. Results:. The von Frey test showed a subpopulation of SCI rats that were hyposensitive to mechanical stimuli from 6 to 8 weeks after injury. The tail flick test showed a subpopulation of SCI rats that were hypersensitive to thermal stimuli at 1 week and 3 to 8 weeks after injury. Although there were no differences in inflammatory cells between subpopulations, we did see significant changes in locomotor recovery between rats with and without sensory abnormalities. Conclusion:. The myeloid cell population at large is not affected by mechanical or thermal phenotypes of pain in this model; however, locomotor recovery is impaired depending on the pain phenotype present. Further investigation into acute inflammatory cells may be insightful for predicting the development of pain phenotypes.