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The purpose of this study was to compare the differences in intramuscular fat content, melanin content, amino acid content and electronic sensory bionic evaluation of the pectoral muscles of five species of black-boned chicken (Taihe black-boned chicken, Yanjin black-boned chicken, Muchuan black-boned chicken, Jiuyuan black-boned chicken and Lueyang black-boned chicken), in order to provide data support for further research on the quality and flavor of local black-boned chickens. The results showed that there were differences between the groups in the intramuscular fat content and melanin content of the breast muscle of the five species of black-boned chicken, showing different gradient gap. Moreover, the relative contents of 14 amino acids, namely, aspartic acid, threonine, serine, glutamic acid, alanine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine and proline were different among groups, among which the contents of amino acids were relatively higher in Lueyang black-boned chickens and Muchuan black-boned chickens. Furthermore, the electronic tongue analysis revealed that the taste of black-boned chicken was mainly fresh, fresh aftertaste and bitter, and there were significant differences in umami aftertaste among different varieties. The Taihe black-boned chicken and Yanjin black-boned chicken had a certain astringent aftertaste. The results of electronic nose detection showed that there were great differences in odor profiles among different breeds of black-boned chickens, and the gap in the odor profiles was the greatest between Yanjin black-boned chicken and the other four varieties, its flavor was the smallest in terms of the sensor response. In summary, the breast muscle of Lueyang black-boned chicken had better quality, it had higher intramuscular fat, melanin content and amino acid ratio, and all of the electronic sensory bionic evaluation response values were relatively higher compared to the other groups. Meanwhile, the different varieties of black-boned chicken had their own outstanding characteristics, and the results of this study would provide the theoretical reference for consumers to purchase black-boned chicken products.

Abstract Carboxy-terminal domain small phosphatase like 2 (CTDSPL2), one of the haloacid dehalogenase phosphatases, is associated with several diseases including cancer. However, the role of CTDSPL2 and its regulatory mechanism in lung cancer remain unclear. Here, we aimed to explore the clinical implications, biological functions, and molecular mechanisms of CTDSPL2 in non-small cell lung cancer (NSCLC). CTDSPL2 was identified as a novel target of the tumor suppressor miR-193a-3p. CTDSPL2 expression was significantly elevated in NSCLC tissues. Database analysis showed that CTDSPL2 expression was negatively correlated with patient survival. Depletion of CTDSPL2 inhibited the proliferation, migration, and invasion of NSCLC cells, as well as tumor growth and metastasis in mouse models. Additionally, silencing of CTDSPL2 enhanced CD4+ T cell infiltration into tumors. Moreover, CTDSPL2 interacted with JAK1 and positively regulated JAK1 expression. Subsequent experiments indicated that CTDSPL2 activated the PI3K/AKT signaling pathway through the upregulation of JAK1, thereby promoting the progression of NSCLC. In conclusion, CTDSPL2 may play an oncogenic role in NSCLC progression by activating PI3K/AKT signaling via JAK1. These findings may provide a potential target for the diagnosis and treatment of NSCLC.

According to a high-temperature compression test of rare earth magnesium alloy (WE43), a strain-compensated constitutive model of the Arrhenius equation based on Zener-Hollomon parameters was established, and the rheological behaviors were predicted. The model exhibited relatively serious prediction distortion in the low-temperature and high-strain rate parameter interval, and its accuracy was still unsatisfactory even after modification by a correction operator considering the coupling of temperature and strain rate. The microstructure characterization and statistical analysis showed that a large number of twinning occurred in the parameter intervals with prediction deviation. The occurrence of twinning complicated the local internal stress distribution by drastically changing the crystal orientation and led to significant fluctuations in the macroscopic strain-stress and hardening curves relative to the rheological processes dominated by the dislocation and softening mechanisms, making the logarithm of the strain rate and stress deviate from the linear relationship. This twinning phenomenon was greatly influenced by the temperature and strain rate. Herein, the influence mechanism on twinning behavior was analyzed from the perspective of the interaction of dislocation and twinning.

Abstract The Qinghai-Tibet Plateau is a valuable genetic resource pool, and the high-altitude adaptation of Tibetan pigs is a classic example of the adaptive evolution of domestic animals. Here, we report the presence of Darwinian positive selection signatures in Tibetan pigs (TBPs) using 348 genome-wide datasets (127 whole-genome sequence datasets (WGSs) and 221 whole-genome single-nucleotide polymorphism (SNP) chip datasets). We characterized a high-confidence list of genetic signatures related response to high-altitude adaptation in Tibetan pigs, including 4,598 candidate SNPs and 131 candidate genes. Functional annotation and enrichment analysis revealed that 131 candidate genes are related to multiple systems and organs in Tibetan pigs. Notably, eight of the top ten novel genes, RALB, NBEA, LIFR, CLEC17A, PRIM2, CDH7, GK5 and FAM83B, were highlighted and associated with improved adaptive heart functions in Tibetan pigs high-altitude adaptation. Moreover, genome-wide association analysis revealed that 29 SNPs were involved in 13 candidate genes associated with at least one adaptive trait. In particular, among the top ten candidate genes, CLEC17A is related to a reduction in hemoglobin (HGB) in Tibetan pigs. Overall, our study provides a robust SNP/gene list involving genetic adaptation for Tibetan pig high-altitude adaptation, and it will be a valuable resource for future Tibetan pig studies.

Abstract Dysfunction of the ubiquitin-proteasome system (UPS) is involved in the pathogenesis of various malignancies including colorectal cancer (CRC). Ubiquitin domain containing 1 (UBTD1), a ubiquitin-like protein, regulates UPS-mediated protein degradation and tumor progression in some cancer types. However, the biological function and mechanism of UBTD1 are far from being well elucidated, and its role in CRC has not been explored yet. In our study, we analyzed CRC patients’ clinical information and UBTD1 expression data, and found that the expression of UBTD1 in cancer tissue was significantly higher than that in adjacent normal tissue. Higher UBTD1 expression was significantly associated with poorer survival and more lymph node metastasis. Overexpression of UBTD1 could facilitate, while knockdown could inhibit CRC cell proliferation and migration, respectively. RNA-seq and proteomics indicated that c-Myc is an important downstream target of UBTD1. Metabolomics showed the products of the glycolysis pathway were significantly increased in UBTD1 overexpression cells. In vitro, we verified UBTD1 upregulating c-Myc protein and promoting CRC cell proliferation and migration via regulating c-Myc. UBTD1 promoted CRC cells’ glycolysis, evidenced by the increased lactate production and glucose uptake following UBTD1 overexpression. Mechanistically, UBTD1 prolonged the half-life of the c-Myc protein by binding to E3 ligase β-transducin repeat-containing protein (β-TrCP), thereby upregulated the expression of glycolysis rate-limiting enzyme hexokinase II (HK2), and enhanced glycolysis and promoted CRC progression. In conclusion, our study revealed that UBTD1 promotes CRC progression by upregulating glycolysis via the β-TrCP/c-Myc/HK2 pathway, suggesting its potential as a prognostic biomarker and therapeutic target in CRC.

Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China. As the monarch drug of Zhigancao decoction, the bioactive molecules of licorice against heart diseases remain elusive. We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides, glycnsisitins A–C (1–3), with distinctive C–C and C–O–C side-chain-to-side-chain linkages from the roots of Glycyrrhiza uralensis (Licorice). Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin (DOX)-induced cardiomyocyte injury. Glycnsisitin A treatment not only reduced the mortality of heart failure (HF) mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis. Gene set enrichment analysis (GSEA) of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium. Mechanistically, glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor (TFRC), which caused increased uptake of iron in cardiomyocytes. These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF, and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.

PD-1/PD-L1 is an important signaling pathway in the adaptive immune system. The CD47/SIRPα signaling pathway is a crucial “do not eat me” signal for innate immunity. This study evaluated the anti-tumor mechanism of IMM2520 in vitro and in vivo. IMM2520 was generated using the “mab-trap” platform. IMM2520 showed high affinity to PD-L1 and relatively lower affinity to CD47, displaying preferential binding to PD-L1 on tumor cells. IMM2520 had the potent ability to inhibit the PD-1/PD-L1 and CD47/SIRPα signaling pathways and killed tumor cells through ADCC and ADCP. Importantly, IMM2520 did not bind to human red blood cells or induce erythrocyte agglutination. IMM2520 demonstrated a tendency to bind to CD47+/PD-L1+ tumor cells, reducing its binding to CD47 single-positive cells. In mouse transplantation models, compared with the first-generation CD47/PD-L1 BsAb (IMM2505), IMM2520 exhibited stronger and dose-dependent antitumor activity. These findings imply that IMM2520 may offer a novel therapeutic alternative for cancer patients.

Background: In recent years, the incidence of acute myeloid leukemia (AML) has increased rapidly with a suboptimal prognosis. In AML, cell death is independent of tumorigenesis, tumor invasion, and drug resistance. PANoptosis is a newly discovered form of cell death that combines pyroptosis, apoptosis, and necroptosis. However, no studies have explored the role of PANoptosis-based signatures in AML. Methods: We screened for PANoptosis-related genes and established a PANoptosis-risk signature using the least absolute shrinkage and selection operator (LASSO) and Cox regression analysis. We combined TCGA, bulk RNA sequencing, and single-cell sequencing to investigate the correlation between candidate genes and the AML tumor microenvironment. Results: The PANoptosis risk signature effectively predicted prognosis with good sensitivity and specificity. The risk score emerged as an independent prognostic factor. Functional enrichment analysis of PANoptosis-related differentially expressed genes suggested that the risk score may be related to cell immunity. Patients with high-risk scores exhibited increased immune cell infiltration, implying a hot tumor immune microenvironment. The risk score was positively correlated with the immune scores and expression levels of immune checkpoints. Therefore, we identified three model factors, BIRC3, PELI1, and PRKACG, as predictors for immunotherapy efficacy. Single-cell sequencing analysis demonstrated that PELI1 and BIRC3 may participate in the regulation of the AML immune microenvironment. Finally, we performed a drug sensitivity analysis to target BIRC3 and PELI1 using molecular docking and molecular dynamics simulations. Conclusion: Our study established and verified a PANoptosis risk signature to predict the survival and immunological treatment response in AML.

Currently, traditional monotherapy for cancer often results in indiscriminate attacks on the body, leading to the emergence of new health problems. To confront these challenges, multimodal combination therapy has become necessary. However, how to develop new smart nanomaterials through green synthesis methods, delivering drugs while simultaneously synergizing multimodal combination therapies for tumor treatment, remains a topic of great significance. In this study, a biomimetic composite nanomaterial (RM-Cu/P) composed of mesoporous polydopamine (MPDA) as the core and red blood cell membranes (RBCMs) as the shell was synthesized as a drug carrier to deliver doxorubicin (DOX) while achieving synergistic chemotherapy, photothermal and chemodynamic therapy (CT/PTT/CDT). Herein, the nanoparticles were extensively characterized to examine their morphological characteristics, elemental composition, and drug-carrying capacity. Notably, the coating of RBCM reduced the toxicity of the RM-Cu/P@DOX nanoparticles, improved their targeting ability and prolonged their circulation time in vivo. The Cu-doped nanoparticles were capable of initiating a Fenton-like reaction to generate reactive oxygen species (ROS) for CDT, while the photothermal conversion efficiency (η) reached 45.20 % under NIR laser irradiation. Subsequently, the particles were examined by in vivo and in vitro experimental studies in cytotoxicity, cellular uptake, ROS levels, lysosomal escape, and mouse tumor model to evaluate their potential application in antitumor. Compared with monotherapy, the RM-Cu/P@DOX nanoparticles had multiple-stimulation response properties under redox, pH, and NIR, which exhibited the advantage of combined trimodal therapy, resulting in remarkable synergistic antitumor efficacy. In conclusion, this innovative platform exhibited promising applications in smart drug delivery and synergistic treatment of cancer.

Summary: Background: Polycystic ovary syndrome (PCOS) represents a prevalent endocrine disorder affecting numerous females worldwide. Dysbiosis of gut microbiota has been linked to the occurrence of PCOS; however, research into the characteristics of gut microbiota in PCOS patients, especially those from different regions and with different testosterone level, remains limited. Additionally, it is still unclear whether gut microbiota helps to distinguish different PCOS subtypes. Methods: We searched four electronic databases (PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov) from Jan 1, 2010 to May 1, 2024. This combined analysis included studies providing the raw data of gut microbiota in PCOS patients. We reanalyzed the characteristics of gut microbiota in PCOS patients from different regions and with different testosterone level. Findings: Fourteen publications satisfying the inclusion criteria were included in the combined analysis. Based on data from 948 individuals, we found alpha-diversity was not significantly different between PCOS and healthy control (HC) groups. However, gut microbiota composition was distinct in PCOS patients compared with healthy individuals. Specifically, Fusobacterium, Ruminococcus_gnavus_group, and Escherichia-Shigella increased, while Dysosmobacter, Schaedlerella, Merdimonas, Clostridiisalibacter, Flintibacter et al. decreased in PCOS women. Regionally, Alistipes was enriched in primarily European patients, while Blautia and Roseburia were more abundant in Chinese patients. Subtype analysis revealed that the gut microbiota of PCOS patients with higher testosterone level (PCOS-HT) differed significantly from those with lower testosterone level (PCOS-LT). Prevotella, Blautia, Dialister, Ruminococcus_torques_group and UCG-002 were enhanced in PCOS-HT patients, while Alistipes, Dysosmobacter, Phocaeicola and Faecalibacterium were diminished. Importantly, a set of eight genera effectively differentiated PCOS-HT patients from PCOS-LT patients with an AUC of 0.95. Interpretation: This systematic anatomization of gut microbiota revealed the microbial characteristics of PCOS patients, particularly those with different testosterone level, thus laying the foundations for further research into pathogenesis of PCOS, and the development of effective diagnostic, treatment, and intervention strategies. Funding: This work was supported by the National Natural Science Foundation of China (No. 81973217, 82260304), the Hainan Province Clinical Medical Center (QWYH202175), and the Specific Research Fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202311).

The genesis and progression of tumors are multifaceted processes influenced by genetic mutations within the tumor cells and the dynamic interplay with their surrounding milieu, which incessantly impacts the course of cancer. The tumor microenvironment (TME) is a complex and dynamic entity that encompasses not only the tumor cells but also an array of non-cancerous cells, signaling molecules, and the extracellular matrix. This intricate network is crucial in tumor progression, metastasis, and response to treatments. The TME is populated by diverse cell types, including immune cells, fibroblasts, endothelial cells, alongside cytokines and growth factors, all of which play roles in either suppressing or fostering tumor growth. Grasping the nuances of the interactions within the TME is vital for the advancement of targeted cancer therapies. Consequently, a thorough understanding of the alterations of TME and the identification of upstream regulatory targets have emerged as a research priority. NF-κB transcription factors, central to inflammation and innate immunity, are increasingly recognized for their significant role in cancer onset and progression. This review emphasizes the crucial influence of the NF-κB signaling pathway within the TME, underscoring its roles in the development and advancement of cancer. By examining the interactions between NF-κB and various components of the TME, targeting the NF-κB pathway appears as a promising cancer treatment approach.

IntroductionResveratrol (Res), a natural plant antitoxin polyphenol, is widely used in animal husbandry due to its antioxidant and anti-inflammatory properties, and current research has focused on humans, sows, and female mice. This study aimed to analyze the effects of dietary Res supplementation in ewes on antioxidant activity, immune responses, hormone levels, rumen microbiota and metabolites across various reproductive stages (estrus, pregnancy, and lactation).MethodsTwenty-four healthy ewe lambs (Hu sheep, 2 months old) with a similar body weight (BW) (mean: 21.79 ± 2.09 kg) were selected and randomly divided into two groups: the control group (Con) and the Res group (Res). The Res group received 10 mg/kg Res (based on BW) in addition to their basal diet.ResultsRes increased the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) in ewes at sexual maturity (p < 0.05). Additionally, Res supplementation induced significant increases in serum glutathione peroxidase (GSH-Px), IgG, FSH, and LH levels during estrus (p < 0.05); serum IgA, IgG and IgM during pregnancy and lactation (p < 0.05); and serum LH, glucose, GSH-Px, and catalase (CAT) levels during lactation (p < 0.05). Meanwhile, serum interleukin 1β (IL-1β) (p =0.005) and cholesterol levels (p = 0.041) during the lactation stage decreased following Res supplementation. Notably, colostrum IgA, IgG, and fat concentrations were significantly higher in the Res group than in the Con group (p < 0.05). Moreover, Res altered the rumen microbiota in ewes. Specifically, the relative abundance of Prevotella (p < 0.05) during pregnancy and Rikenellaceae_RC9_gut_group (p < 0.001) during lactation were significantly increased in ewes under Res treatment. The abundance of Rikenellaceae_RC9_gut_group was positively correlated with the levels of Ig A, Ig M, E2, FSH, LH, GSH-PX, and CAT. Additionally, Res altered the activity of metabolic pathways such as progesterone-mediated oocyte maturation, the estrogen signaling pathway, ovarian steroidogenesis, and the AMPK signaling pathway, and the levels of AICAR and 2-hydroxyestradiol metabolites, both during pregnancy and lactation.DiscussionThere findings show that Res can improve health, antioxidant status, and immune activity throughout the reproductive cycle in ewes by regulating rumen microorganisms and metabolites.

Zearalenone (ZEN) contamination in cereals poses a serious threat to human and animal health, yet existing rapid test methods still suffer from poor stability and low sensitivity. The studied sensor reduces inspection time while enabling applications for on-site grain inspection. Specifically, a ZEN detector that can sensitively detect ZEN content in grains was developed. Ion implantation is an effective method for modifying screen-printed electrodes (SPEs). Gold nanoparticles (AuNPs; 5–10 nm) were uniformly implanted using screen-printed electrodes as a catalytic oxidation medium to generate an electrochemical sensor. The surface structure of the modified electrode was characterized using scanning electron microscopy and X-ray photoelectron spectroscopy. The results showed that differential pulse voltammetry had good linear electrochemical response to ZEN at 10 ng/kg to 10 mg/kg, with a detection limit of 1.1 ng/kg. We used AuNP-SPE sensors to detect ZEN in grain samples such as maize and oats.

Chinese multinational enterprises (CMNEs) are increasingly initiating risky mergers and acquisitions (M&As) in developed markets to obtain strategic assets, which necessitates long-term integration that often takes years. Drawing on knowledge management literature, this study explores CMNEs’ dynamic post-merger integration (PMI) changes, the role of knowledge, and coevolutionary relationships. Based on 41 conversations concerning five Chinese acquisitions in Germany, this study develops a spiral-forward framework, determining that CMNEs’ PMI changes proceed through three phases of access, adjustment, and growth, moving from autonomy to systemic integration to business integration in a forward spiral with evolving knowledge needs. The efficiency of previous integration and knowledge needs has an influence in the following periods’ degree of integration via balanced integration, over-integration, or delayed integration. This study stresses the crucial role of knowledge types and knowledge processes in CMNEs’ PMI changes, offering a valuable framework for understanding CMNEs’ PMI dynamics and the role of knowledge management.

The present study describes a new species within the genus Cultellus Schumacher, 1817 collected from the South China Sea. An integrative taxonomic approach incorporating morphological comparisons, geometric morphometrics and genetic analyses was used to identify and differentiate the new species. Cultellus exilis sp. nov. is distinguished from its congeners by its slender, fragile and translucent valves, curved posteroventral margins and relatively large protractor scars. The geometric morphometric analyses, based on outlines data, indicated that samples of Cultellus exilis sp. nov. clustered together and were distinctly separated from other species. Multiple species delimitation results, based on the mitochondrial COI gene, support the separation of Cultellus exilis sp. nov. from its related congeners. Phylogenetic analyses of a nuclear (28S rRNA) and two mitochondrial (COI, 16S rRNA) genes using Maximum Likelihood and Bayesian Inference methods revealed that the species belongs to the genus Cultellus. The superfamily Solenoidea Lamarck, 1809, which includes the families Solenidae Lamarck, 1809 and Pharidae H. Adams & A. Adams, 1856, exhibits closer affinity to the family Hiatellidae Gray, 1824 than to Solecurtidae d’Orbigny, 1846. Furthermore, we found that the genus Siliqua was clustered alongside the genera Ensiculus and Phaxas as a sister clade, which contradicts the current systematics of the subfamily within the family Pharidae. This work highlights the utility of integrative taxonomy for species identification, recognition and phylogenetic investigation.

Objectives: The purpose of this article is to utilize video images for the examination of lower limb biomechanics in tennis players while executing forehand and backhand strokes, providing a reference for training. Methods: This article provides a brief introduction to forehand and backhand strokes in the sport of tennis. Subsequently, a biomechanical analysis of the lower limbs during forehand and backhand strokes was conducted on ten level 2 tennis players and ten specialized tennis students at XX Sports University. Findings: Level 2 athletes who have undergone a long training exhibited higher linear velocity and joint torque in the lower-limb joints during the preparatory and striking phases of forehand and backhand strokes. Additionally, they exhibited more pronounced surface electromyographic signals in the rectus femoris muscle of the lower limbs. Novelty:The novelty of this article lies in the use of video imagery, a non-contact and non-intrusive method that does not affect the athletes' movements, to study the biomechanics of their lower limbs. Doi: 10.28991/HIJ-2024-05-01-07 Full Text: PDF

Abstract As one of the most attractive next‐generation probiotics, mucin‐degrading Akkermansia muciniphila has emerged as an essential and integral factor in maintaining human health and affecting pathological outcomes. Its abundance is inversely associated with various metabolic diseases (e.g., obesity and type 2 diabetes), cardiovascular diseases, and intestinal inflammation. Supplementing A. muciniphila to restore the gut microbiota ecosystem is a promising approach for treating metabolic disorders. However, the direct utilization of this probiotic is limited by technological and regulatory hurdles, such as the in vitro bulk culture of A. muciniphila and the need for expensive animal‐derived materials. Therefore, enrichment of A. muciniphila using nutraceutical supplements is a feasible strategy. Dietary supplements, especially medicinal herbs, offer a vast and valuable resource as potential prebiotics for promoting the growth of A. muciniphila in the gut, ensuring reliable safety and efficacy. In this study, we first systemically reviewed the dietary substances and medicinal foods known to promote A. muciniphila from over 100 literature sources, aiming to establish a candidate basis for future exploration of prebiotics targeting A. muciniphila. Furthermore, we summarized and discussed the major regulatory factors and mechanisms responsible for the beneficial effect of A. muciniphila on metabolic disorders, hoping to open up exciting directions for in‐depth research on the pharmacological mechanism of A. muciniphila and pave the way for its clinical therapeutics.

Adipokine chemerin plays important roles in disorders of glucose and lipid metabolism of obesity and obesity-related diseases, and exercise-induced improvement of glucose and lipid metabolism is closely related to the decrease of chemerin, but the mechanisms by which chemerin regulates glucose and lipid metabolism remain unclarified. Hypotestosterone induces male obesity and disorders of glucose and lipid metabolism through androgen receptor (AR) and its target genes: glucose and lipid metabolism-related molecules (including FOXO1, PEPCK, PGC-1α, and SCD1). Recently, the link between them has been reported that chemerin modulated the secretion of androgen. In this study, global chemerin knockout (chemerin (−/−)) mice were established to demonstrate the roles of chemerin in regulating blood glucose and blood lipid of mice under diet (high-fat (HFD) and normal diet) and exercise interventions and then to explore its mechanisms (AR – glucose and lipid metabolism enzymes). We found that the blood lipid and adipocyte size were low accompanied by the improvements in the levels of serum testosterone, gastrocnemius AR, and gastrocnemius FOXO1, SCD1, and PGC-1α in HFD chemerin (−/−) mice, but exercise-induced improvements of these indicators in HFD WT mice were attenuated or abolished in HFD chemerin (−/−) mice. In conclusion, the decrease of chemerin improved the blood lipid profile of HFD male mice at sedentary and exercise states, mediated partly by the increases of testosterone and AR to regulate glucose and lipid metabolism enzymes. To our knowledge, it is the first report that chemerin’s regulation of glucose and lipid metabolism might be mediated by testosterone and AR in vivo.

High-entropy alloys (HEAs) exhibit extraordinary physical properties such as superior strength-to-weight ratios and enhanced corrosion and oxidation resistance, making them potentially useful in energy storage and generation industries. However, thermal and mechanical properties of HEAs with various compositions vary significantly. Furthermore, these properties have rarely been investigated simultaneously owing to material or instrumentation limitations. Herein, we synthesize an HEA (AlCrNbSiTi) coating with a thickness of less than 2 μm. We customize a frequency-domain photothermal testing system to characterize the thermal and mechanical properties of the proposed coating with high accuracy. Owing to the large mixing enthalpy of the Al-Ti, Nb-Si, and Ti-Si pairs in the coating, its hardness and elastic modulus are 15.2 and 254.7 GPa, respectively which are higher than those of previously reported HEAs. The thermal conductivity of the AlCrNbSiTi coating is characterized to be 2.90 W·m−1·K−1, within the expected range and well explained by the free-electron consistency diversity and phonon scattering from the amorphous structure. Additionally, the coating exhibits adequate wear performance, with a wear rate of 5.4 × 10−8 mm3·N−1·m−1. This relatively low thermal conductivity, combined with extraordinary mechanical properties, makes the proposed material an excellent candidate as a protective coating material for nuclear reactor components which require high strength, irradiation resistance, and thermal protection.

Background: With the increase in basketball competition intensity, video image analysis-based methods have been increasingly applied to improve the technical level of basketball players. Methods: Taking the example of one-handed set shoulder shooting (the basketball player spreads legs apart at shoulder width, holds the ball over the right shoulder, extends the right hand along with lower body movement, and releases the ball softly using fingers), this study compared the technical differences between 20 level 2 basketball players (level 2 group) and 20 basketball specialized students (specialized group) by capturing video images using a high-speed camera and conducting independent sample t-tests. Results: The level 2 group had a significantly higher shooting percentage than the specialized group (p=0.005). Additionally, the level 2 group had shorter dribbling time and longer shooting time compared to the specialized group (p=0.032; p=0.021). The amplitude of variation in the knee, hip, and elbow joints was significantly greater than that of the specialized group (p=0.008/0.016/0.031). The flexion angles of the index finger and middle finger after striking in the level 2 group were significantly higher than those of the specialized group (p=0.021/0.036). The level 2 group also had a smaller striking angle and a larger striking height and speed than the specialized group (p=0.001; p=0.005/0.006). Conclusion: Athletes of different levels show differences in phase duration and joint angles when performing one-handed set shoulder shooting, providing a basis for athletes' training.

Beef flavor profiles are strongly influenced by cooking methods and lipid composition. However, the effect of instant-boiling on the aroma of different beef slices was unclear. This study investigated the lipid profiles and instant-boiling volatile profiles of chuck tender (M. Supraspinatus), sirloin (M. Longissimus dorsi) and silverside (M. Biceps femoris). Quantitative lipidomics identified 336 lipid molecular species, of which 84–112 were quantitatively different among the three beef slices. Sirloin had lower phosphatidylcholine, phosphatidylinositol, phosphatidylglycerol and free fatty acids than chuck tender and silverside. The unsaturated fatty acid acyl chains in phosphatidylethanolamine differed significantly. Solid phase microextraction-gas chromatography-olfactometry-mass spectrometry (SPME-GC-O-MS) identified hexanal, octanal, nonanal, decanal, (E)-2-octenal, (E)-2-nonenal, (E)-2-undecenal, (E,E)-2,4-nonadienal, (E,E)-2,4-decadienal, 1-octen-3-ol, 2-pentylfuran and acetoin as the aroma-active compounds of instant-boiled beef. Unsaturated free fatty acids and phosphatidylglycerols with unsaturated fatty acid residues positively correlated with the aroma-active compounds and might be crucial in flavor differences among the three beef slices. These findings provide greater understanding of the lipid and instant-boiling aroma-active compound profiles in chuck tender, sirloin and silverside, and reflect the suitability of different beef slices for instant-boiling from the aroma perspective.

Technological innovation is changing the way maritime transport is done, and automated driving is one of the hot topics, including unmanned ships that use automated driving technology, but legal challenges to the application of unmanned ships in the shipping industry must be resolved before that happens—whether and how the principles of existing international conventions regarding unmanned ships. To deal with this problem, it is far from enough to rely on the efforts of international organizations or the revision of international conventions. The paper analyzes several typical legal issues faced by unmanned ships: the legal definition of unmanned ships, the seaworthiness of unmanned ships, the master and crew rules, and the collision and rescue of unmanned ships, taking China as an example, the paper explains reasonable and effective legal path of domestic and international laws, trying to seek solutions at the level of domestic law beyond international convention. The paper concludes that the traditional navigation rules have largely been developed to meet the needs of manned transportation, and cannot be fully applied to unmanned ships. Therefore, until there is an international regulation specifically for unmanned ships, it would be appropriate to interpret or revise existing international conventions to apply to unmanned ships. And for countries including China, it is important to consider the improvement of domestic laws.

Abstract Oxidative stress and the immune microenvironment both contribute to the pathogenesis of esophageal squamous cell carcinoma (ESCC). However, their interrelationships remain poorly understood. We aimed to examine the status of key molecules involved in oxidative stress and the immune microenvironment, as well as their relationships with each other and with clinicopathological features and prognosis in ESCC. The expression of programmed death‐ligand 1 (PD‐L1), CD8, nuclear factor erythroid‐2 related factor‐2 (NRF2), and NAD(P)H quinone oxidoreductase 1 (NQO1) was detected using immunohistochemistry in tissue samples from 176 patients with ESCC. We employed both combined positive score (CPS) and tumor proportion score (TPS) to evaluate PD‐L1 expression and found a positive correlation between CPS and TPS. Notably, PD‐L1 expression, as assessed by either CPS or TPS, was positively correlated with both NRF2 nuclear score and NQO1 score in stage II–IV ESCC. We also observed a positive correlation between the density of CD8+ T cells and PD‐L1 expression. Furthermore, high levels of PD‐L1 CPS, but not TPS, were associated with advanced TNM stage and lymph node metastases. Moreover, both PD‐L1 CPS and the nuclear expression of NRF2 were found to be predictive of shorter overall survival in stage II–IV ESCC. By using the Mandard‐tumor regression grading (TRG) system to evaluate the pathological response of tumors to neoadjuvant chemotherapy (NACT), we found that the TRG‐5 group had higher NRF2 nuclear score, PD‐L1 CPS, and TPS in pre‐NACT biopsy samples compared with the TRG‐3 + 4 group. The NQO1 scores of post‐NACT surgical specimens were significantly higher in the TRG‐5 group than in the TRG 3 + 4 group. In conclusion, the expression of PD‐L1 is associated with aberrant NRF2 signaling pathway, advanced TNM stage, lymph node metastases, and unfavorable prognosis. The dysregulation of PD‐L1 and aberrant activation of the NRF2 signaling pathway are implicated in resistance to NACT. Our findings shed light on the complex interrelationships between oxidative stress and the immune microenvironment in ESCC, which may have implications for personalized therapies and improved patient outcomes.

The contamination of water by arsenic (As) has emerged as a significant environmental concern due to its well-documented toxicity. Environmentally relevant concentrations of As have been reported to pose a considerable threat to fish. However, previous studies mainly focused on the impacts of As at environmentally relevant concentrations on adult fish, and limited information is available regarding its impacts on fish at early life stage. In this study, zebrafish embryos were employed to evaluate the environmental risks following exposure to different concentrations (0, 25, 50, 75 and 150 μg/L) of pentavalent arsenate (AsV) for 120 hours post fertilization. Our findings indicated that concentrations ≤ 150 μg/L AsV did not exert significant effects on survival or aberration; however, it conspicuously inhibited heart rate of zebrafish larvae. Furthermore, exposure to AsV significantly disrupted mRNA transcription of genes associated with cardiac development, and elongated the distance between the sinus venosus and bulbus arteriosus at 75 μg/L and 150 μg/L treatments. Additionally, AsV exposure enhanced superoxide dismutase (SOD) activity at 50, 75 and 150 μg/L treatments, and increased mRNA transcriptional levels of Cu/ZnSOD and MnSOD at 75 and 150 μg/L treatments. Concurrently, AsV suppressed metallothionein1 (MT1) and MT2 mRNA transcriptions while elevating heat shock protein70 mRNA transcription levels in zebrafish larvae resulting in elevated malondialdehyde (MDA) levels. These findings provide novel insights into the toxic effects exerted by low concentrations of AsV on fish at early life stage, thereby contributing to an exploration into the environmental risks associated with environmentally relevant concentrations.

Background: Tyrosine kinase inhibitors (TKIs) are standard first-line treatments for advanced non-small-cell lung cancer (NSCLC) with driver gene mutations. The Response Evaluation Criteria in Solid Tumors (RECIST) are limited in predicting long-term patient benefits. A tumour marker-based evaluation criteria, RecistTM, was used to investigate the potential for assessing targeted-therapy efficacy in lung cancer treatment. Methods: We retrospectively analysed patients with stage IIIA–IV NSCLC and driver gene mutations, whose baseline tumour marker levels exceeded the pre-treatment cut-off value three-fold and who received TKI-targeted therapy as a first-line treatment. We compared efficacy, progression-free survival (PFS), and overall survival (OS) between RecistTM and RECIST. Findings: The median PFS and OS differed significantly among treatment-response subgroups based on RecistTM but not RECIST. The predicted 1-, 2-, and 3-year disease-progression risk, according to area under the receiver operating characteristic curve, as well as the 1-, 3-, and 5-year mortality risk, differed significantly between RecistTM and RECIST. The median PFS and OS of tmCR according to RecistTM, was significantly longer than (CR+PR) according to RECIST. Imaging analysis revealed that the ΔPFS was 11.27 and 6.17 months in the intervention and non-intervention groups, respectively, suggesting that earlier intervention could extend patients' PFS. Interpretation: RecistTM can assess targeted-therapy efficacy in patients with advanced NSCLC and driver gene mutations, along with tumour marker abnormalities. RecistTM surpasses RECIST in predicting short- and long-term patient benefits, and allows the early identification of patients resistant to targeted drugs, enabling prompt intervention and extending the imaging-demonstrated time to progression.

BackgroundCD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs).MethodsFive suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 “mAb-trap” platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems.ResultsUsing hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a “mAb-trap” platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605–26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605–12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605–12C10 efficiently eradicated all established tumors in all mice.ConclusionA panel of BsAbs targeting CD38 and CD47 developed based on the “mAb-tarp” platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.

Abstract Inferior air stability is a primary barrier for large‐scale applications of garnet electrolytes in energy storage systems. Herein, a deeply hydrated hydrogarnet electrolyte generated by a simple ion‐exchange‐induced phase transition from conventional garnet, realizing a record‐long air stability of more than two years when exposed to ambient air is proposed. Benefited from the elimination of air‐sensitive lithium ions at 96 h/48e sites and unobstructed lithium conduction path along tetragonal sites (12a) and vacancies (12b), the hydrogarnet electrolyte exhibits intrinsic air stability and comparable ion conductivity to that of traditional garnet. Moreover, the unique properties of hydrogarnet pave the way for a brand‐new aqueous route to prepare lithium metal stable composite electrolyte on a large‐scale, with high ionic conductivity (8.04 × 10−4 S cm−1), wide electrochemical windows (4.95 V), and a high lithium transference number (0.43). When applied in solid‐state lithium batteries (SSLBs), the batteries present impressive capacity and cycle life (164 mAh g−1 with capacity retention of 89.6% after 180 cycles at 1.0C under 50 °C). This work not only designs a new sort of hydrogarnet electrolyte, which is stable to both air and lithium metal but also provides an eco‐friendly and large‐scale fabrication route for SSLBs.

Proton exchange membrane fuel cells (PEMFCs) should further reduce the platinum consumption to lower their manufacturing costs and life-cycle carbon emissions. However, the performance of the catalyst layers with low-Pt loading needs to be improved. Short-side-chain (SSC) ionomers have been proven to enhance the catalytic activity of conventional catalyst layers. In this work, the SSC ionomer was applied to the electrospun catalyst layer, and achieved a remarkable improvement in the performance. With the use of commercially available catalyst, the membrane electrode assemblies (MEAs) prepared in this work exhibited a low total-Pt-consumption of 0.064 g kW−1 (stoichiometric ratios of 1.5/2.5 for H2/air, 80°C, 100 kPa) and achieved the 2025 target proposed by the US Department of Energy. Separating activation, ohmic, and concentration overpotentials, the performance enhancement of the electrospun catalyst layer mainly came from the decrease of ohmic overpotential and concentration overpotential. The electrospun ionomer membrane without catalyst was used as a research model to explore the proton transport properties inside the electrospun catalyst layer. The results showed that in the range of PEMFC operating temperature, the proton conductivity of the electrospun catalyst layer could be higher, but meanwhile the proton-conduction activation energy was also elevated. Compared with the conventional catalyst layer, the electrospun catalyst layer showed obviously better performance before and after accelerated stress test, thus verifying the practicality of the electrospun catalyst layers. This work provided a reference for the development of low platinum and high performance catalyst layers.

In this study, the epididymal histology, caepididymal sperm physiological parameters, serum reproductive hormones, and antioxidant enzyme SOD levels of Tibetan sheep at a 2500 m and 3500 m altitude were compared by using a combination of transcriptome and metabolomics methods. This was conducted to investigate the effects of a high-altitude environment on spermatogenesis and the maturation of Tibetan sheep. The results showed that compared to the low-altitude group, the high-altitude group had a smaller epididymal lumen, thicker epididymal wall, significantly decreased sperm survival rate, and significantly increased sperm deformation rate, but no difference in sperm motility and sperm respiratory intensity. With increasing altitude, Tibetan sheep showed a decreasing trend in serum reproductive hormones (FSH and T), while the antioxidant enzyme SOD activity was significantly reduced. Transcriptomic analysis revealed 139 differentially expressed genes in the Tibetan sheep epididymis under high-altitude conditions. The SYCP2 gene is involved in multiple biological processes related to reproduction and plays an important role in the regulation of epididymal function and sperm quality in Tibetan sheep. Genes like ADCYAP1R1, CABP2, CALN1, and ATP6V1B1 can help maintain sperm viability and maturation by regulating the cAMP signaling pathway, calcium ion homeostasis, and cellular signaling. Metabolomic analysis found that the high-altitude group had increased adenosine content and decreased prostaglandin I2 content in the epididymis. These metabolites are involved in spermatogenesis, motility, fertilization, and early embryonic development. The integrated omics analysis suggests that Tibetan sheep adapt to the high-altitude hypoxic environment by regulating cAMP signaling pathway genes like ADCY and PRKACA, as well as metabolites like adenosine and prostaglandin I2, to maintain epididymal function and sperm motility. These genes and metabolites play an important role in maintaining normal epididymal function and sperm motility at high altitudes.

Drug prediction and treatment using bioinformatics and large-scale modeling have emerged as pivotal research areas. This study proposes a novel multi-level collaboration framework named Syn-COM for feature extraction and data integration of diseases and drugs. The framework aims to explore optimal drug combinations and interactions by integrating molecular virtuality, similarity clustering, overlap area, and network distance. It uniquely combines the characteristics of Chinese herbal medicine with clinical experience and innovatively assesses drug interaction and correlation through a synergy matrix. Gouty arthritis (GA) was used as a case study to validate the framework’s reliability, leading to the identification of an effective drug combination for GA treatment, comprising Tamaricis Cacumen (Si = 0.73), Cuscutae Semen (Si = 0.68), Artemisiae Annuae Herba (Si = 0.62), Schizonepetae Herba (Si = 0.73), Gleditsiae Spina (Si = 0.89), Prunellae Spica (Si = 0.75), and Achyranthis Bidentatae Radix (Si = 0.62). The efficacy of the identified drug combination was confirmed through animal experiments and traditional Chinese medicine (TCM) component analysis. Results demonstrated significant reductions in the blood inflammatory factors IL1A, IL6, and uric acid, as well as downregulation of TGFB1, PTGS2, and MMP3 expression (p < 0.05), along with improvements in ankle joint swelling in GA mice. This drug combination notably enhances therapeutic outcomes in GA by targeting key genes, underscoring the potential of integrating traditional medicine with modern bioinformatics for effective disease treatment.

This study analyzes the performance degradation of traditional hybrid wind turbines under high blade-tip-speed ratio conditions and proposes solutions through two-dimensional Computational Fluid Dynamics (CFD) simulations. It also introduces the design of two innovative asynchronous-hybrid dual-rotor wind turbines. The results indicate a remarkable 98.5% enhancement in torque performance at low blade-tip-speed ratios with the hybrid wind turbine model. However, as the blade-tip-speed ratio increases, it leads to negative torque generation within the inner rotor of the conventional design, resulting in a reduction of the power coefficient by up to 13.1%. The introduction of the new wind turbine design addresses this challenge by eliminating negative torque at high blade-tip-speed ratios through adjustments in the inner rotor’s operating range. This modification not only rectifies the negative torque issue but also enhances the performance of the outer rotor in the leeward region, consequently boosting the overall power coefficient. Moreover, the optimized inner rotor configuration effectively disrupts and shortens the wake length by 16.7%, with this effect intensifying as the rotational speed increases. This optimization is pivotal for enhancing the efficiency of multi-machine operations within wind farms.

Liver cancer is one of the most prevalent forms of cancer worldwide. A significant proportion of patients with hepatocellular carcinoma (HCC) are diagnosed at advanced stages, leading to unfavorable treatment outcomes. Generally, the development of HCC occurs in distinct stages. However, the diagnostic and intervention markers for each stage remain unclear. Therefore, there is an urgent need to explore precise grading methods for HCC. Machine learning has emerged as an effective technique for studying precise tumor diagnosis. In this research, we employed random forest and LightGBM machine learning algorithms for the first time to construct diagnostic models for HCC at various stages of progression. We categorized 118 samples from GSE114564 into three groups: normal liver, precancerous lesion (including chronic hepatitis, liver cirrhosis, dysplastic nodule), and HCC (including early stage HCC and advanced HCC). The LightGBM model exhibited outstanding performance (accuracy = 0.96, precision = 0.96, recall = 0.96, F1-score = 0.95). Similarly, the random forest model also demonstrated good performance (accuracy = 0.83, precision = 0.83, recall = 0.83, F1-score = 0.83). When the progression of HCC was categorized into the most refined six stages: normal liver, chronic hepatitis, liver cirrhosis, dysplastic nodule, early stage HCC, and advanced HCC, the diagnostic model still exhibited high efficacy. Among them, the LightGBM model exhibited good performance (accuracy = 0.71, precision = 0.71, recall = 0.71, F1-score = 0.72). Also, performance of the LightGBM model was superior to that of the random forest model. Overall, we have constructed a diagnostic model for the progression of HCC and identified potential diagnostic characteristic gene for the progression of HCC.

Motivation: Genomic structural variation refers to chromosomal level variations such as genome rearrangement or insertion/deletion, which typically involve larger DNA fragments compared to single nucleotide variations. Deletion is a common type of structural variants in the genome, which may lead to mangy diseases, so the detection of deletions can help to gain insights into the pathogenesis of diseases and provide accurate information for disease diagnosis, treatment, and prevention. Many tools exist for deletion variant detection, but they are still inadequate in some aspects, and most of them ignore the presence of chimeric variants in clustering, resulting in less precise clustering results.Results: In this paper, we present LcDel, which can detect deletion variation based on clustering and long reads. LcDel first finds the candidate deletion sites and then performs the first clustering step using two clustering methods (sliding window-based and coverage-based, respectively) based on the length of the deletion. After that, LcDel immediately uses the second clustering by hierarchical clustering to determine the location and length of the deletion. LcDel is benchmarked against some other structural variation detection tools on multiple datasets, and the results show that LcDel has better detection performance for deletion. The source code is available in https://github.com/cyq1314woaini/LcDel.

Objectives: Multi-Criteria Decision Analysis (MCDA) has gained increasing attention in supporting drug risk-benefit assessment, pricing and reimbursement, as well as optimization of clinical interventions. The objective of this study was to systematically collect and categorize evaluation criteria and techniques of weighting and scoring of MCDA for drug value assessment.Methods: A systematic review of the literature was conducted across seven databases to identify articles utilizing the MCDA frameworks for the evaluation of drug value. Evaluation criteria mentioned in the included studies were extracted and assigned to 5 dimensions including clinical, economic, innovative, societal and humanistic value. A descriptive statistical analysis was performed on the identified drug value evaluation criteria, as well as the weighting and scoring techniques employed. The more a criterion or technique were mentioned in articles, the more important we consider it.Results: Out of the 82 articles included, 111 unique criteria were identified to evaluate the value of drug. Among the 56 unique criteria (448 times) used to measure clinical value, the most frequently mentioned were “comparative safety/tolerability” (58 times), “comparative effectiveness/efficacy” (56 times), “comparative patient-perceived health/patient reported outcomes” (37 times), “disease severity” (34 times), and “unmet needs” (25 times). Regarding economic value measurement, out of the 20 unique criteria (124 times), the most frequently utilized criteria were “cost of intervention” (17 times), “comparative other medical costs” (16 times), and “comparative non-medical costs” (18 times). Out of the 10 criteria (18 times) for assessing innovative value, “a novel pharmacological mechanism” was the most frequently mentioned criterion (5 times). Among the 22 criteria (73 times) used to measure societal value, “system capacity and appropriate use of intervention” was the most frequently cited criterion (14 times). Out of the 3 criteria (15 times) utilized to measure humanistic value, “political/historical/cultural context” was the most frequently mentioned criterion (9 times). Furthermore, 11 scoring and 11 weighting techniques were found from various MCDA frameworks. “Swing weighting” and “a direct rating scale” were the most frequently used techniques in included articles.Conclusion: This study comprehensively presented the current evaluation dimensions, criteria, and techniques for scoring and weighting in drug-oriented MCDA articles. By highlighting the frequently cited evaluation criteria and techniques for scoring and weighting, this analysis will provide a foundation to reasonably select appropriate evaluation criteria and technique in constructing the MCDA framework that aligns with research objectives.

Background Sepsis can disrupt immune regulation and lead to acute respiratory distress syndrome (ARDS) frequently. Remazolam, a fast-acting hypnotic drug with superior qualities compared to other drugs, was investigated for its potential protective effects against sepsis-induced ARDS. Methods Forty Sprague-Dawley rats were randomly divided into four groups, including the sepsis + saline group, sham operation + saline group, sham operation + remazolam group and the sepsis + remazolam group. Lung tissues of rats were extracted for HE staining to assess lung damage, and the wet weight to dry weight (W/D) ratio was calculated. The levels of proinflammatory factors, anti-inflammatory factors, CD4+ and CD8+ T cells in peripheral blood, MDA, MPO, and ATP in the lung tissue were measured by using ELISA. Western blotting was performed to determine the protein expression of HMGB1 in lung tissues. Results In comparison to the sham operation + saline and sham operation + remazolam groups, the sepsis + saline group exhibited significantly higher values for W/D ratio, lung damage score, IL-1β, IL-6, TNF-α, PCT, CRP, MDP and MPO, while exhibiting lower levels of CD4+ and CD8+ T lymphocytes, PaO2, PCO2, and ATP. The rats in the sepsis + saline group displayed ruptured alveolar walls and evident interstitial lung edema. However, the rats in the sepsis + remazolam group showed improved alveolar structure. Furthermore, the HMGB1 protein expression in the sepsis + remazolam group was lower than the sepsis + saline group. Conclusion Remazolam can alleviate the inflammatory response in infected rats, thereby alleviating lung injury and improving immune function, which may be attributed to the reduction in HMGB1 protein expression.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent arterial and venous thrombosis, habitual fetal miscarriages, often accompanied by mild to moderate thrombocytopenia, and persistent moderate-to-high titer positivity for antiphospholipid antibodies (aPLs). However, patients with antiphospholipid antibodies may also present with several nonthrombotic clinical manifestations, such as thrombocytopenia, cardiac valve disease, nephropathy, skin ulcers, or cognitive dysfunction, which are collectively referred to as nonstandard manifestations of APS. Of these, for APS with predominantly cutaneous ulcers, previous reports have focused on APS with combined cutaneous vasculitis, and its medical treatment, rather than cutaneous ulcers with predominantly fatty inflammatory lesions, and the associated surgical treatment. Here, we admitted a relatively rare case of primary APS with extensive skin ulceration of the right lower extremity, without cutaneous vasculitis, in the presence of extensive and severe inflammatory lipoatrophy, carrying anti-β2-glycoprotein I and lupus anticoagulant, which is reported as follows, with a view to raising awareness of this disease.

Subcortical band heterotopia (SHB) is a rare severe brain developmental malformation caused by deficient neuronal migration during the development of cerebral cortex. Here, a human induced pluripotent stem cell (iPSCs) line was established from a 4-year-1-month-old girl with SHB carrying a heterozygous mutation (c.568A > G, p.K190E) in DCX. The generated iPSC line showed the ability to differentiate into three lineages in vitro and was confirmed by pluripotency markers and the original gene mutation.

Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV, #615075), a rare autosomal dominant genetic disorder caused by heterozygous mutation in the CTNNB1 gene, is characterized by global developmental delay, impaired intellectual development, axial hypotonia, and dysmorphic craniofacial features with microcephaly. Here, we established an iPSC line (SDQLCHi055-A) from a patient with NEDSDV carrying a heterozygote mutation (c.854 T > A, p.L285*) in the CTNNB1 gene. The iPSC line has typical iPSCs characteristics, including pluripotency and trilineage differentiation hallmarks.

Canavan disease (CD, OMIM# 271900) is an autosomal recessive neurodegenerative disorder caused by homozygous or compound heterozygous mutations in ASPA gene, which result in catalytic deficiency of the aspartoacylase enzyme and the accumulation of N-acetylaspartic acid (NAA). Clinical presentation varies according to the age of disease onset. Here, we generated a human induced pluripotent stem cell line (hiPSCs) SDQLCHi064-A from a 5-month old boy with CD carrying two novel frame shift mutations c.556_559dupGTTC (p.L187Rfs*5) and c.919delA (p.S307Vfs*24) of the ASPA gene, in order for us to better understanding the disease.

Zwitterionic hydrogels, with their unique antibacterial and tissue-adhesive nature, show great potential in the fields of wearable sensors, healthcare monitoring, and e-skins. However, it remains a huge challenge to integrate high elasticity and low hysteresis in such a hydrogel via simple methods. Herein, a novel tissue-adhesive zwitterionic hydrogel sensor was fabricated by a simple one-pot method using copolymerization of [2-(Methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA), N-[Tris (hydroxymethyl)methyl] acrylamide (THMA), and acrylic acid (AA), which was crosslinked by polyethylene glycol diglycidyl ether (PEGDE), a crosslinker famous for its low-toxicity and biocompatibility. The obtained SAT hydrogel shows robust elasticity with low hysteresis and fatigue resistance, which is essential for the long-term use. The introduction of THMA and PAA enhances the adhesive strength and reversible resilience of the hydrogel by interfacial hydrogen bonding, resulting in superior adhesion to skin without causing harm. The chemical crosslinker existing in SAT hydrogel enables it to withstand large deformations while maintaining stability. Besides the well-known antibacterial properties, the addition of SBMA enables the hydrogel to exhibit excellent electrical properties and a rapid response (19.5 ms) within a wide strain-sensing range, which facilitates accurate detection of various human body motions, such as joint bending, swallowing, and heartbeats. Moreover, the hydrogel demonstrates biocompatibility and excellent antibacterial activity, promising a safer and more comfortable experience for users.

Introduction: Zearalenone-14-glucoside (Z14G) is a modified mycotoxin that widely contaminates food across the world. Our preliminary experiment showed that Z14G degrades to zearalenone (ZEN) in the intestine exerting toxicity. Notably, oral administration of Z14G in rats induces intestinal nodular lymphatic hyperplasia. Objectives: To investigate the mechanism of Z14G intestinal toxicity and how it differs from ZEN toxicity. We conducted a precise toxicology study on the intestine of rats exposed to Z14G and ZEN using multi-omics technology. Methods: Rats were exposed to ZEN (5 mg/kg), Z14G-L (5 mg/kg), Z14G-H (10 mg/kg), and pseudo germ free (PGF)-Z14G-H (10 mg/kg) for 14 days. Histopathological studies were performed on intestines from each group and compared. Metagenomic, metabolomic, and proteomic analyses were performed on rat feces, serum, and intestines, respectively. Results: Histopathological studies showed that Z14G exposure resulted in dysplasia of gut-associated lymphoid tissue (GALT) compared to ZEN exposure. The elimination of gut microbes in the PGF-Z14G-H group alleviated or eliminated Z14G-induced intestinal toxicity and GALT dysplasia. Metagenomic analysis revealed that Z14G exposure significantly promoted the proliferation of Bifidobacterium and Bacteroides compared to ZEN. Metabolomic analysis showed that Z14G exposure significantly reduced bile acid, while proteomic analysis found that Z14G exposure significantly reduced the expression of C-type lectins compared to ZEN. Conclusions: Our experimental results and previous research suggest that Z14G is hydrolyzed to ZEN by Bifidobacterium and Bacteroides promoting their co-trophic proliferation. This leads to inactivation of lectins by hyperproliferative Bacteroides when ZEN caused intestinal involvement, resulting in abnormal lymphocyte homing and ultimately GALT dysplasia. It is noteworthy that Z14G is a promising model drug to establish rat models of intestinal nodular lymphatic hyperplasia (INLH), which is of great significance for studying the pathogenesis, drug screening and clinical application of INLH.

Abstract Long non-coding RNAs (lncRNAs) play important roles in many pathophysiological processes, including cancer progression. Namely, lncRNA Receptor-tyrosine-kinase-like orphan receptor-1 antisense 1 (ROR1-AS1) is crucial for cancer occurrence and progression in organs such as the liver or bladder. However, its expression and role in cholangiocarcinoma (CCA) have not been thoroughly explored. Firstly, we assessed cell viability, proliferation, invasion, and migration using three cell lines (HuCCT-1, QBC399, and RBE) to explore the biological characteristics of ROR1-AS1 in CCA. Secondly, to determine the in vivo effect of ROR1-AS1 on tumor growth, ROR1-AS1 knockdown (KD) HuCCT-1 cells were subcutaneously injected into nude mice to evaluate tumor growth. Finally, we conducted a bioinformatic analysis to confirm the role of ROR1-AS1 in the prognosis and immunity of CCA. In this study, we found that lncRNA ROR1-AS1 was increased in CCA samples and patients with higher ROR1-AS1 expression had a shorter overall survival period. siRNA-mediated KD of ROR1-AS1 significantly reduced cell proliferation and inhibited the migration of CCA cells. In addition, ROR1-AS1 KD HuCCT-1 cells injected into nude mice grew slower than normal CCA cells. In summary, our results show that ROR1-AS1 can promote CCA progression and might serve as a new target for diagnosis and treatment of CCA.

The electrochemical reduction of CO2 is an extremely potential technique to achieve the goal of carbon neutrality, but the development of electrocatalysts with high activity, excellent product selectivity, and long-term durability remains a great challenge. Herein, the role of metal-supports interaction (MSI) between different active sites (including single and bimetallic atom sites consisting of Cu and Ni atoms) and carbon-based supports (including C2N, C3N4, N-coordination graphene, and graphdiyne) on catalytic activity, product selectivity, and thermodynamic stability towards CO2 reduction reaction (CRR) is systematically investigated by first principles calculations. Our results show that MSI is mainly related to the charge transfer behavior from metal sites to supports, and different MSI leads to diverse magnetic moments and d-band centers. Subsequently, the adsorption and catalytic performance can be efficiently improved by tuning MSI. Notably, the bimetallic atom supported graphdiyne not only exhibits a better catalytic activity, higher product selectivity, and higher thermodynamic stability, but also effectively inhibits the hydrogen evolution reaction. This finding provides a new research idea and optimization strategy for the rational design of high-efficiency CRR catalysts.

The emergence of safe and functional eggs for consumer acceptance has gained focus. The production of carotenoid-enriched eggs has received attention due to its multifunctional biological properties. Nutritional modification of laying hens’ diet can be a strategy to produce such eggs. This review presents the chemistry of carotenoids in nature and eggs, the accumulation process of carotenoids into eggs, and the functions of carotenoids in eggs. Our findings showed that carotenoids can be deposited into the egg and contribute to improving its nutritive value. The biosynthesis, chemical structure, and metabolism pathways of carotenoids lead to the deposition of carotenoids into eggs in their original or metabolized forms. Also, some factors modulate the efficiency of carotenoids in fowls before accumulation into eggs. Carotenoid-enriched eggs may be promising, ensuring the availability of highly nutritive eggs. However, further studies are still needed to comprehend the full metabolism process and the extensive functions of carotenoids in eggs.

Aquatic animals frequently undergo feed deprivation and starvation stress. It is well-known that the gut microbiota and the gut–brain short neuropeptide F (sNPF) play essential roles in diet restriction. Therefore, investigating the responses of the gut microbiota and sNPF can enhance our understanding of physiological adaptations to feed deprivation and starvation stress. In this study, we examined the alterations in the gut microbiota of juvenile mud crabs under feed deprivation and starvation conditions. The results reveal differences in the richness and diversity of gut microbiota among the satisfied, half food, and starvation groups. Moreover, the microbial composition was affected by starvation stress, and more than 30 bacterial taxa exhibited significantly different abundances among the three feeding conditions. These results indicate that the diversity and composition of the gut microbiota are influenced by diet restriction, potentially involving interactions with the gut–brain sNPF. Subsequently, we detected the location of sNPF in the brains and guts of mud crabs through immunofluorescence and investigated the expression profile of sNPF under different feeding conditions. The results suggest that sNPF is located in both the brains and guts of mud crabs and shows increased expression levels among different degrees of diet restriction during a 96 h period. This study suggested a potential role for sNPF in regulating digestive activities and immunity through interactions with the gut microbiota. In conclusion, these findings significantly contribute to our understanding of the dynamic changes in gut microbiota and sNPF, highlighting their interplay in response to diet restriction.

Examining dual vertical-axis wind turbines (VAWTs) across various turbulence scenarios is crucial for advancing the efficiency of urban energy generation and promoting sustainable development. This study introduces a novel approach by employing two-dimensional numerical analysis through computational fluid dynamics (CFD) software to investigate the performance of VAWTs under varying turbulence intensity conditions, a topic that has been relatively unexplored in existing research. The analysis focuses on the self-starting capabilities and the effective utilization of wind energy, which are key factors in urban wind turbine deployment. The results reveal that while the impact of increased turbulence intensity on the self-starting performance of VAWTs is modest, there is a significant improvement in wind energy utilization within a specific turbulence range, leading to an average power increase of 1.41%. This phenomenon is attributed to the more complex flow field induced by heightened turbulence intensity, which delays the onset of dynamic stall through non-uniform aerodynamic excitation of the blade boundary layer. Additionally, the inherent interaction among VAWTs contributes to enhanced turbine output power. However, this study also highlights the trade-off between increased power and the potential for significant fatigue issues in the turbine rotor. These findings provide new insights into the optimal deployment of VAWTs in urban environments, offering practical recommendations for maximizing energy efficiency while mitigating fatigue-related risks.

Unmanned sailboats can convert wind energy with sails to provide power for navigation, which can independently plan routes and collect data without human intervention. They have received increasing attention in recent years due to their low power consumption and strong self-sustainability. Due to the greater difficulty of manipulation, the unmanned sailboats have a weaker maneuverability than the propeller-driven vessels in the complex and variable marine environment. Typically, the turning motion is evaluated to characterize the maneuverability of a vessel, which has rarely been investigated in the existing research on unmanned sailboats. Therefore, this study builds a motion simulation platform for unmanned sailboats based on the 3 m class Petrel Sail to investigate the turning characteristics. The index of the approximate turning circle is introduced based on the turning motion trajectory, which is used to obtain the effect of rudder angle, wind angle, wind speed, and current speed on the turning performance of the sailboat in ideal hydrostatic conditions and under flow disturbance, respectively. Finally, a harbor pool test is conducted with an unmanned sailboat to verify the analysis results, and the errors in maximum transverse distance and maximum advance distance are in the reasonable range, proving the correctness of the theoretical results. The current study also provides theoretical guidance for subsequent research on sailboat manipulation and maneuverability.

This study aimed to evaluate the effects of arginine (0.5%, 1%, 1.5%, 2%, and 2.5% arginine supplementation levels were selected) on the ovarian development of Pacific white shrimp (Litopenaeus vannamei). The analyzed arginine supplementation levels in each diet were 2.90%, 3.58%, 4.08%, 4.53%, 5.04%, and 5.55%, respectively. A total of 540 shrimp (an initial weight of approximately 14 g) with good vitality were randomly distributed into six treatments, each of which had three tanks (300 L in volume filled with 200 L of water), with 30 shrimp per duplicate. Shrimp were fed three times a day (6:00 a.m., 11:00 a.m., and 6:00 p.m.). The results showed that after the 12-week raring cycle, shrimp fed with 4.08% and 4.53% Arg achieved better ovary development, which was identified by ovarian stage statistics, ovarian morphology observation, serum hormone levels (methylfarneside (MF); 5-hydroxytryptamine (5-HT); estradiol (E2); and gonadotropin-releasing hormone (GnRH)), gene expression (DNA meiotic recombinase 1 (dmc1), proliferating cell nuclear antigen (pcna), drosophila steroid hormone 1 (cyp18a), retinoid X receptor (rxra), and ecdysone receptor (ecr)). Further in-depth analysis showed that 4.08% and 4.53% Arg supplementation increased the concentration of vitellogenin in hepatopancreas and serum (p < 0.05) and upregulated the expression level of hepatopancreatic vg and vgr (p < 0.05), which promoted the synthesis of hepatopancreas exogenous vitellogenin and then transported it into the ovary through the vitellogenin receptor and further promoted ovarian maturation in L. vannamei. Meanwhile, compared with the control group, the expression level of vg in the ovary of the 4.53% Arg group was significantly upregulated (p < 0.05), which indicated endogenous vitellogenin synthesis in ovarian maturation in L. vannamei. Moreover, the expression of genes related to the mechanistic target of the rapamycin complex 1 (mTORC1) pathway and protein levels was regulated by dietary arginine supplementation levels. Arginine metabolism-related products, including nitric oxide synthase (NOS), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP), were also affected. RNA interference was applied here to study the molecular regulation mechanism of arginine on ovarian development in L. vannamei. A green fluorescent protein (GFP)-derived double-stranded RNA (dsGFP) is currently commonly used as a control, while TOR-derived dsRNA (dsTOR) and NOS-derived dsRNA (dsNOS) were designed to build the TOR and NOS in vivo knockdown model. The results showed that the mTORC1 and NO-sGC-cGMP pathways were inhibited, while the vitellogenin receptor and vitellogenin gene expression levels were downregulated significantly in the hepatopancreas and ovary. Overall, dietary arginine supplementation could enhance endogenous and exogenous vitellogenin synthesis to promote ovary development in L. vannamei, and the appropriate dosages were 4.08% and 4.53%. The NO-sGC-cGMP and mTORC1 signaling pathways mediated arginine in the regulation of ovary development in L. vannamei.

iGABAR, a member of the Cys-loop ligand-gated ion channel superfamily, is a significant target of the insecticide ivermectin (IVM). GRD is the potential subunit of the insect iGABAR. However, little information about GRD in Ae. aegypti has been reported. In this study, we involved cloning and characterizing the iGABAR subunit GRD of Ae. aegypti (Ae-GRD). Sequence analysis indicated that Ae-GRD, as part of the cysteine-loop ligand-gated ion channel family, is similar to other insect GRD. RNA interference (RNAi) was employed to explore IVM resistance in Ae. aegypti, resulting in a significant reduction in Ae-GRD expression (p < 0.05), and the mortality of Ae. aegypti adults with Ae-GRD knockdown was significantly decreased after exposure to ivermectin. Bioinformatics prediction identified miR-71-5p as a potential regulator of Ae-GRD. In vitro, dual-luciferase reporter assays confirmed that Ae-GRD expression was regulated by miR-71-5p. Microinjection of miR-71-5p mimics upregulated miR-71-5p expression and downregulated Ae-GRD gene expression, reducing mortality by 34.52% following IVM treatment. Conversely, microinjection of a miR-71-5p inhibitor decreased miR-71-5p expression but did not affect the susceptibility to IVM despite increased Ae-GRD expression (p < 0.05). In conclusion, Ae-GRD, as one of the iGABA receptor subunits, is a potential target of ivermectin. It may influence ivermectin resistance by modulating the GABA signaling pathway. The inhibition of Ae-GRD expression by miR-71-5p decreased ivermectin resistance and consequently lowered the mortality rate of Ae. aegypti mosquitoes. This finding provides empirical evidence of the relationship between Ae-GRD and its miRNA in modulating insecticide resistance, offering novel perspectives for mosquito control strategies.