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Abstract The initial spin periods of newborn magnetars are strongly associated with the origin of their strong magnetic fields, both of which can affect the electromagnetic radiation and gravitational waves (GWs) emitted at their birth. Combining the upper limit $$E_{\textrm{SNR}}\lesssim 10^{51}$$ E SNR ≲ 10 51 erg on the explosion energies of the supernova (SN) remnants around slowly-spinning magnetars with a detailed investigation on the evolution of newborn magnetars, we set constraints on the initial spin periods of magnetars born in weak SN explosions. Depending on the conversion efficiency $$\eta $$ η of the electromagnetic energy of these newborn magnetars into the kinetic energy of SN ejecta, the minimum initial spin periods of these newborn magnetars are $$P_{\textrm{i, min}}\simeq 5$$ P i, min ≃ 5 –6 ms for an ideal efficiency $$\eta =1$$ η = 1 , $$P_{\textrm{i, min}}\simeq 3$$ P i, min ≃ 3 –4 ms for a possible efficiency $$\eta =0.4$$ η = 0.4 , and $$P_{\textrm{i, min}}\simeq 1$$ P i, min ≃ 1 –2 ms for a relatively low efficiency $$\eta =0.1$$ η = 0.1 . Based on these constraints and adopting reasonable values for the physical parameters of the newborn magnetars, we find that their GW radiation at $$\nu _{\textrm{e,1}}=\nu $$ ν e,1 = ν may be undetectable by the Einstein Telescope (ET) since the maximum signal-to-noise ratio ( $$\mathrm{S/N}$$ S / N ) is only 2.41 even the sources are located at a very close distance of 5 Mpc, where $$\nu $$ ν are the spin frequencies of the magnetars. At such a distance, the GWs emitted at $$\nu _{\textrm{e,2}}=2\nu $$ ν e,2 = 2 ν from the newborn magnetars with dipole fields $$B_{\textrm{d}}=5\times 10^{14}$$ B d = 5 × 10 14 and $$10^{15}$$ 10 15 G may be detectable by the ET because $$\mathrm{S/N}$$ S / N are 10.01 and 19.85, respectively. However, if these newborn magnetars are located at 20 Mpc away in the Virgo supercluster, no GWs could be detected by the ET due to low $$\mathrm{S/N}$$ S / N .

Abstract Background Glehnia littoralis F. Schmidt ex Miq., an endangered plant species with significant medicinal, edible, and ecological value, is now a central concern for conservation and sustainable utilization. Investigating the physiological and ecological mechanisms leading to its endangerment and elucidating its genetic background constitutes the foundation for conducting in-depth research on G. littoralis. Results Our observations have revealed a significant degree of floral sterility in wild populations of G. littoralis. The inflorescences of G. littoralis are classified into three types: completely fertile, completely sterile, and partially fertile compound umbels. Moreover, the flowers of G. littoralis can be categorized into fertile and sterile types. Sterile flowers exhibited abnormalities in the stigma, ovary, and ovules. This study is the first to discover that the presence or absence of a giant cell at the funiculus during the initiation of ovule primordium determines whether the flower can develop normally, providing cytological evidence for female sterility in G. littoralis. Conversely, both fertile and sterile flowers produced normally developed pollen. Field observations have suggested that robust plants bear more fertile umbels, while weaker ones have fewer or even no fertile umbels, indicating a close relationship between flower fertility and plant nutritional status. Our model correctly predicted that the eastern coastal regions of China, as well as prospective areas in Neimenggu and Sichuan, are suitable environments for its cultivation. Additionally, Using flow cytometry and genome survey, we estimated the genome size of G. littoralis to be 3.06 Gb and the heterozygosity to be 4.58%. Conclusion The observations and findings presented in this study were expected to provide valuable insights for further conserving its genetic resources and sustainable utilization of G. littoralis.

Abstract Background Addressing the shortage of high-quality protein resources, this study was conducted to investigate the effects of replacing soybean meal (SBM) with different levels of enzymolysis-fermentation compound protein feed (EFCP) in the diets of growing-finishing pigs, focusing on growth performance, nutrients digestibility, carcass traits, and meat quality. Methods Sixty DLY (Duroc × Landrace × Yorkshire) pigs with an initial body weight of 42.76 ± 2.05 kg were assigned to 5 dietary treatments in a 2 × 2 + 1 factorial design. These dietary treatments included a corn-soybean meal diet (CON), untreated compound protein feed (UCP) substitution 50% (U50) and 100% SBM (U100) diets, and EFCP substitution 50% (EF50) and 100% SBM (EF100) diets. Each treatment had 6 pens (replicates) with 2 pigs per pen, and the experiment lasted 58 d, divided into phase I (1–28 d) and phase II (29–58 d). Following phase I, only the CON, U50, and EF50 groups were continued for phase II, each with 5 replicate pens. On d 59, a total of 15 pigs (1 pig/pen, 5 pens/treatment) were euthanized. Results During phase I, the EF50 group had a higher average daily gain (ADG) in pigs (P

The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs. The bile acids with varying levels within two types of pigs were found and then in vitro experiments were conducted to identify whether these bile acids can directly affect lipid accumulation. Fourteen pigs, including seven lean and seven obese pigs with body weights of approximately 80 kg, were fed the same diet at an amount approximately equivalent to 3% of their respective body weights daily for 42 d. In vitro, 3T3-L1 preadipocytes were cultured in medium with high glucose levels and were differentiated into mature adipocytes using differentiation medium. Then, bile acids were added to mature adipocytes for 4 d. The results showed that there was a difference in body lipids levels and gut microbiota composition between obese and lean pigs (P

Abstract Aims/Introduction We investigated the relationship of circulating TSP‐1 mRNA and miR‐194 with diabetic kidney disease’s degree. Materials and Methods We enrolled 167 hospitalized type 2 diabetes patients in the endocrinology department. Patients were split into three groups according to urinary microalbumin: A, B and C. The control group comprised healthy outpatients (n = 163). The quantities of microribonucleic acid (miR)‐194 and thrombospondin‐1 (TSP‐1) messenger ribonucleic acid (mRNA) in the participants’ circulation were measured using a quantitative real‐time polymerase chain reaction. Results Circulating TSP‐1 mRNA (P = 0.024) and miR‐194 (P = 0.029) expressions significantly increased in type 2 diabetes patients. Circulating TSP‐1 mRNA (P = 0.040) and miR‐194 (P = 0.007) expression levels differed significantly among the three groups; circulating TSP‐1 mRNA expression increased with urinary microalbumin. However, miR‐194 declined in group B and increased in group C. Circulating TSP‐1 mRNA was positively correlated with cystatin‐c (r = 0.281; P = 0.021) and microalbumin/creatinine ratio (UmALB/Cr; r = 0.317; P = 0.009); miR‐194 was positively correlated with UmALB/Cr (r = 0.405; P = 0.003). Stepwise multivariate linear regression analysis showed cystatin‐c (β = 0.578; P = 0.021) and UmALB/Cr (β = 0.001; P = 0.009) as independent factors for TSP‐1 mRNA; UmALB/Cr (β = 0.005; P = 0.028) as an independent factor for miR194. Areas under the curve for circulating TSP‐1 mRNA and miR194 were 0.756 (95% confidence interval 0.620–0.893; sensitivity 0.69 and specificity 0.71, P

Abstract Background Appropriate iron supplementation is essential for neonatal growth and development. However, there are few reports on the effects of iron overload on neonatal growth and immune homeostasis. Thus, the aim of this study was to investigate the effects of iron nutrition on neonatal growth and intestinal immunity by administering different levels of iron to neonatal pigs. Results We found that iron deficiency and iron overload resulted in slow growth in neonatal pigs. Iron deficiency and iron overload led to down-regulation of jejunum intestinal barrier and antioxidant marker genes, and promoted CD8+ T cell differentiation in jejunum and mesenteric lymph nodes (MLN) of pigs, disrupting intestinal health. Moreover, iron levels altered serum iron and tissue iron status leading to disturbances in redox state, affecting host innate and adaptive immunity. Conclusions These findings emphasized the effect of iron nutrition on host health and elucidated the importance of iron in regulating redox state and immunity development. This study provided valuable insights into the regulation of redox state and immune function by iron metabolism in early life, thus contributing to the development of targeted interventions and nutritional strategies to optimize iron nutrition in neonates.

Abstract Background Nanoplastics (NPs) are emerging pollutants that pose risks to living organisms. Recent findings have unveiled the reproductive harm caused by polystyrene nanoparticles (PS-NPs) in female animals, yet the intricate mechanism remains incompletely understood. Under this research, we investigated whether sustained exposure to PS-NPs at certain concentrations in vivo can enter oocytes through the zona pellucida or through other routes that affect female reproduction. Results We show that PS-NPs disrupted ovarian functions and decreased oocyte quality, which may be a contributing factor to lower female fertility in mice. RNA sequencing of mouse ovaries illustrated that the PI3K-AKT signaling pathway emerged as the predominant environmental information processing pathway responding to PS-NPs. Western blotting results of ovaries in vivo and cells in vitro showed that PS-NPs deactivated PI3K-AKT signaling pathway by down-regulating the expression of PI3K and reducing AKT phosphorylation at the protein level, PI3K-AKT signaling pathway which was accompanied by the activation of autophagy and apoptosis and the disruption of steroidogenesis in granulosa cells. Since PS-NPs penetrate granulosa cells but not oocytes, we examined whether PS-NPs indirectly affect oocyte quality through granulosa cells using a granulosa cell–oocyte coculture system. Preincubation of granulosa cells with PS-NPs causes granulosa cell dysfunction, resulting in a decrease in the quality of the cocultured oocytes that can be reversed by the addition of 17β-estradiol. Conclusions This study provides findings on how PS-NPs impact ovarian function and include transcriptome sequencing analysis of ovarian tissue. The study demonstrates that PS-NPs impair oocyte quality by altering the functioning of ovarian granulosa cells. Therefore, it is necessary to focus on the research on the effects of PS-NPs on female reproduction and the related methods that may mitigate their toxicity.

Abstract Rare‐earth permanent magnet synchronous machines face challenges in manipulating their magnetic fields, which hinders the ability to extend the operation speed range. Moreover, this inflexibility leads to reduced efficiency in high‐speed scenarios when the machine is under flux‐weakening control and increases the risk of the magnets becoming demagnetised. The authors propose an alterable‐magnetic‐circuit variable‐flux memory machine (AMC‐VFMM) and a multi‐objective hierarchical optimisation method is conducted to optimise the machine. Firstly, the topology and alterable‐magnetic‐circuit principle of the proposed AMC‐VFMM are introduced. Then, optimisation objectives including torque production capability, flux regulation capability, and resisting unintentional demagnetisation capability are defined, and the hierarchical optimisation approach is established by stratifying the optimisation objectives and variables through the sensitivity analysis. Finite element analysis indicates that electromagnetic performances of the optimised design scheme are significantly enhanced. The bench test of the prototype demonstrates the superiority of the proposed AMC‐VFMM and validates the effectiveness of the optimisation design method.

Abstract Background The calmodulin (CaM) and calmodulin-like (CML) proteins play regulatory roles in plant growth and development, responses to biotic and abiotic stresses, and other biological processes. As a popular fruit and ornamental crop, it is important to explore the regulatory mechanism of flower and fruit development of passion fruit. Results In this study, 32 PeCaM/PeCML genes were identified from passion fruit genome and were divided into 9 groups based on phylogenetic analysis. The structural analysis, including conserved motifs, gene structure and homologous modeling, illustrates that the PeCaM/PeCML in the same subgroup have relative conserved structural features. Collinearity analysis suggested that the expansion of the CaM/CML gene family likely took place mainly by segmental duplication, and the whole genome replication events were closely related with the rapid expansion of the gene group. PeCaM/PeCMLs were potentially required for different floral tissues development. Significantly, PeCML26 had extremely high expression levels during ovule and fruit development compared with other PeCML genes, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. The co-presence of various cis-elements associated with growth and development, hormone responsiveness, and stress responsiveness in the promoter regions of these PeCaM/PeCMLs might contribute to their diverse regulatory roles. Furthermore, PeCaM/PeCMLs were also induced by various abiotic stresses. This work provides a comprehensive understanding of the CaM/CML gene family and valuable clues for future studies on the function and evolution of CaM/CML genes in passion fruit. Conclusion A total of 32 PeCaM/PeCML genes were divided into 9 groups. The PeCaM/PeCML genes showed differential expression patterns in floral tissues at different development stages. It is worth noting that PeCML26, which is highly homologous to AtCaM2, not only interacts with multiple BBR-BPC TFs, but also has high expression levels during ovule and fruit development, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. This research lays the foundation for future investigations and validation of the potential function of PeCaM/PeCML genes in the growth and development of passion fruit.

Abstract Accumulating evidence from observational studies have suggested an association between gastroesophageal reflux disease (GERD) and non-alcoholic fatty liver disease (NAFLD). However, due to that such studies are prone to biases, we imported Mendelian randomization (MR) to explore whether the causal association between two diseases exsit. Hence, we aimed to analysis the potential association with MR. The single nucleotide polymorphisms (SNPs) of GERD were retrieved from the genome-wide association study dataset as the exposure. The SNPs of NAFLD were taken from the FinnGen dataset as the outcome. The relationship was analyzed with the assistance of inverse variance weighted, MR-Egger, and weighted median. We also uitilized the MR-Egger intercept, Cochran’s Q test, leave-one-out analysis, MR-PRESSO, and Steiger directionality test to evaluate the robustness of the causal association. The meta-analysis were also implemented to give an overall evaluation. Finally, our analysis showed a causal relationship between GERD and NAFLD with aid of MR and meta-analysis (OR 1.71 95% CI 1.40–2.09; P

The use of next-generation probiotics (NGP) in pigs for combating diseases has been subject to limited research. Here we explored the potential of a well-known NGP candidate Akkermansia muciniphila targeting pig gut health. In the first screening experiment, we found that the abundance of A. muciniphila peaked at 14 d old but decreased at weaning (21 d old; P

Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.

IntroductionBenzoic acid (BA) could be added to the diets of weaned pigs to prevent diarrhea due to its antibacterial function. However, BA may be absorbed or decomposed before it can reach the hindgut. This study was conducted to explore the effect of a novel coated benzoic acid (CBA) on growth performance, immunity, and intestinal barrier functions in weaned pigs upon enterotoxigenic Escherichia coli (ETEC) challenge.MethodsIn a 21d experiment, 32 piglets were randomly assigned to 4 treatments: (1) a basal diet (CON), (2) CON added with CBA at 3 g/kg (CBA); (3) CON and challenged by ETEC (ECON); (4) CON added with CBA at 3 g/kg and challenged by ETEC (ECON). On d 22, all piglets were euthanised to obtain samples.ResultsDietary CBA supplementation elevated the average daily gain (ADG) of the ETEC-challenged pigs (p < 0.05). CBA also improved the digestibility of dry matter, gross energy, and ash (p < 0.05). Moreover, CBA elevated the ratio of blood basophil and the serum concentration of total cholesterol of the ETEC challenged pigs (p < 0.05). Importantly, CBA increased the serum concentrations of immunoglobulin A (IgA), IgG, and IgM (p < 0.05). CBA not only decreased the crypt depth but also increased the ratio of villus height to crypt depth (V:C) in the jejunum and ileum (p < 0.05). Moreover, CBA increased the activities of jejunal and ileal sucrase, and the activities of duodenal and ileal maltase (p < 0.05). Importantly, CBA elevated the expression levels of critical functional genes such as the claudin-1, occluding, glucose transporter-2 (GLUT2), and sodium/glucose cotransporter-1 (SGLT-1) in the jejunal epithelium upon ETEC challenge (p < 0.05). Additionally, CBA increased the abundances of total bacteria and Bacillus, and increased the concentrations of volatile fatty acids (acetic acid, propanoic acid, and butyric acid) in cecum (p < 0.05).DiscussionThese results suggested a beneficial role for CBA in alleviating intestinal injury in weaned pigs following ETEC challenge. Such effects may be tightly associated with elevated immunity and improved intestinal epithelium functions and microbiota.

Abstract l-Threonine is an important feed additive with the third largest market size among the amino acids produced by microbial fermentation. The GRAS (generally regarded as safe) industrial workhorse Corynebacterium glutamicum is an attractive chassis for l-threonine production. However, the present l-threonine production in C. glutamicum cannot meet the requirement of industrialization due to the relatively low production level of l-threonine and the accumulation of large amounts of by-products (such as l-lysine, l-isoleucine, and glycine). Herein, to enhance the l-threonine biosynthesis in C. glutamicum, releasing the aspartate kinase (LysC) and homoserine dehydrogenase (Hom) from feedback inhibition by l-lysine and l-threonine, respectively, and overexpressing four flux-control genes were performed. Next, to reduce the formation of by-products l-lysine and l-isoleucine without the cause of an auxotrophic phenotype, the feedback regulation of dihydrodipicolinate synthase (DapA) and threonine dehydratase (IlvA) was strengthened by replacing the native enzymes with heterologous analogues with more sensitive feedback inhibition by l-lysine and l-isoleucine, respectively. The resulting strain maintained the capability of synthesizing enough amounts of l-lysine and l-isoleucine for cell biomass formation but exhibited almost no extracellular accumulation of these two amino acids. To further enhance l-threonine production and reduce the by-product glycine, l-threonine exporter and homoserine kinase were overexpressed. Finally, the rationally engineered non-auxotrophic strain ZcglT9 produced 67.63 g/L (17.2% higher) l-threonine with a productivity of 1.20 g/L/h (108.0% higher) in fed-batch fermentation, along with significantly reduced by-product accumulation, representing the record for l-threonine production in C. glutamicum. In this study, we developed a strategy of reconstructing the feedback regulation of amino acid metabolism and successfully applied this strategy to de novo construct a non-auxotrophic l-threonine producing C. glutamicum. The main end by-products including l-lysine, l-isoleucine, and glycine were almost eliminated in fed-batch fermentation of the engineered C. glutamicum strain. This strategy can also be used for engineering producing strains for other amino acids and derivatives.

Rotaviruses (RV) are a major cause of severe gastroenteritis, particularly in neonatal piglets. Despite the availability of effective vaccines, the development of antiviral therapies for RV remains an ongoing challenge. Retinoic acid (RA), a metabolite of vitamin A, has been shown to have anti-oxidative and antiviral properties. However, the mechanism by which RA exerts its intestinal-protective and antiviral effects on RV infection is not fully understood. The study investigates the effects of RA supplementation in Duroc × Landrace × Yorkshire (DLY) piglets challenged with RV. Thirty-six DLY piglets were assigned into six treatments, including a control group, RA treatment group with two concentration gradients (5 and 15 mg/d), RV treatment group, and RV treatment group with the addition of different concentration gradients of RA (5 and 15 mg/d). Our study revealed that RV infection led to extensive intestinal architecture damage, which was mitigated by RA treatment at lower concentrations by increasing the villus height and villus height/crypt depth ratio (P

Magnetite (Fe3O4) particles have been widely reported to enhance the anammox's activity in anammox granular sludge (AnGS), yet the underlying mechanisms remain unclear. This study demonstrates that both Fe3O4 microparticles (MPs) and nanoparticles (NPs) at a dosage of 200 mg Fe3O4/L significantly increased the specific anammox activity (SAA) of AnGS. Additionally, the transcriptional activities of the hzs and hdh genes involved in the anammox process, as well as the heme c content in AnGS, were also notably enhanced. Notably, Fe3O4 NPs were more effective than MPs in boosting anammox activity within AnGS. Mechanistically, Fe3O4 MPs released free iron, which anammox bacteria utilized to promote the synthesis of key enzymes, thereby enhancing their activity. Compared to MPs, Fe3O4 NPs not only elevated the synthesis of these key enzymes to a higher level but also induced a nanofluids effect on the surface of AnGS, improving substrate permeability and accessibility to intragranular anammox bacteria. Moreover, the nanofluids effect was identified as the primary mechanism through which Fe3O4 NPs enhanced anammox activity within AnGS. These findings provide new insights into the effects of nanoparticles on granular sludge systems, extending beyond AnGS.

Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund’s adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.

Enteric infection is a major cause of enteric disorder in neonatal pigs during the weaning transition. Dihydromyricetin (DMY) is a natural flavanonol compound extracted from Ampelopsis grossedentata with numerous biological activities such as antioxidative and immunomodulatory functions. The objective of this study was to investigate the effects of dietary dihydromyricetin supplementation on growth performance, immunity, and intestinal functions in weaned pigs challenged by enterotoxigenic Escherichia coli (ETEC). In total, 24 weaned DLY (Duroc × Landrace × Yorkshire) pigs were allotted to 3 treatments. Pigs fed with basal diet or basal diet containing 300 mg/kg DMY were orally infused with sterilized culture or ETEC (2.5 × 1011 colony-forming units). Dietary DMY supplementation significantly elevated the final weight and average daily gain (ADG) but reduced diarrhea incidence in the weaned pigs of the EDMY group compared to the pigs of the ECON group (p

It is increasingly recognized that microplastics (MPs) are being transmitted through the food chain system, but little is known about the microorganisms involved in MP degradation, functional biodegradation genes, and metabolic pathways of degradation in the intestinal tract of foodborne animals. In this study, we explored the potential flora mainly involved in MP degradation in the intestinal tracts of Taoyuan, Duroc, and Xiangcun pigs by macrogenomics, screened relevant MP degradation genes, and identified key enzymes and their mechanisms. The pig colon was enriched with abundant MP degradation-related genes, and gut microorganisms were their main hosts. The fiber diet did not significantly affect the abundance of MP degradation-related genes but significantly reduced their diversity. We identified a total of 94 functional genes for MP degradation and classified them into 27 categories by substrate type, with polystyrene (PS), polyethylene terephthalate (PET), and di(2-ethylhexyl) phthalate (DEHP) were the most predominant degradation types. The MP degradation functional genes were widely distributed in a variety of bacteria, mainly in the phylum Firmicutes and Bacteroidetes. Based on the identified functional genes for MP degradation, we proposed a hypothetical degradation mechanism for the three major MP pollutants, namely, PS, PET, and DEHP, which mainly consist of oxidoreductase, hydrolase, transferase, ligase, laccase, and isomerase. The degradation process involves the breakdown of long polymer chains, the oxidation of short-chain oligomers, the conversion of catechols, and the achievement of complete mineralization. Our findings provide insights into the function of MP degradation genes and their host microorganisms in the porcine colon.

Summary: Although more and more evidence has supported that metabolic syndrome (MS) is linked to ischemic stroke (IS), the molecular mechanism and genetic association between them has not been investigated. Here, we combined the existing single-cell RNA sequencing (scRNA-seq) data and mendelian randomization (MR) for stroke to understand the role of dysregulated metabolism in stroke. The shared hub genes were identified with machine learning and WGCNA. A total of six upregulated DEGs and five downregulated genes were selected for subsequent analyses. Nine genes were finally identified with random forest, Lasso regression, and XGBoost method as a potential diagnostic model. scRNA-seq also show the abnormal glycolysis level in most cell clusters in stroke and associated with the expression level of hub genes. The genetic relationship between IS and MS was verified with MR analysis. Our study reveals the common molecular profile and genetic association between ischemic stroke and metabolic syndrome.

Summary: The medial entorhinal cortex (MEC) is crucial for contextual memory, yet its role in context-induced retrieval of morphine withdrawal memory remains unclear. This study investigated the role of the MEC and its projection neurons from MEC layer 5 to the basolateral amygdala (BLA) (MEC−BLA neurons) in context-induced retrieval of morphine withdrawal memory. Results show that context activates the MEC in morphine withdrawal mice, and the inactivation of the MEC inhibits context-induced retrieval of morphine withdrawal memory. At neural circuits, context activates MEC−BLA neurons in morphine withdrawal mice, and the inactivation of MEC−BLA neurons inhibits context-induced retrieval of morphine withdrawal memory. But MEC−BLA neurons are not activated by conditioning of context and morphine withdrawal, and the inhibition of MEC−BLA neurons do not influence the coupling of context and morphine withdrawal memory. These results suggest that MEC−BLA neurons are critical for the retrieval, but not for the formation, of morphine withdrawal memory.

Metabolic disorders are highly prevalent in modern society. Exercise mimetics are defined as pharmacological compounds that can produce the beneficial effects of fitness. Recently, there has been increased interest in the role of eugenol and transient receptor potential vanilloid 1 (TRPV1) in improving metabolic health. The aim of this study was to investigate whether eugenol acts as an exercise mimetic by activating TRPV1. Here, we showed that eugenol improved endurance capacity, caused the conversion of fast-to-slow muscle fibers, and promoted white fat browning and lipolysis in mice. Mechanistically, eugenol promoted muscle fiber-type transformation by activating TRPV1-mediated CaN signaling pathway. Subsequently, we identified IL-15 as a myokine that is regulated by the CaN/nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway. Moreover, we found that TRPV1-mediated CaN/NFATc1 signaling, activated by eugenol, controlled IL-15 levels in C2C12 myotubes. Our results suggest that eugenol may act as an exercise mimetic to improve metabolic health via activating the TRPV1-mediated CaN signaling pathway.

A 42-days study was conducted to evaluate the effects of different dietary types (corn-or wheat-soybean meal-based diet) and phytase (Phy) or a multi-carbohydrase and phytase complex (MCPC) supplementation on growth performance, digestibility of phosphorus (P), intestinal transporter gene expression, plasma indexes, bone parameters, and fecal microbiota in growing pigs. Seventy-two barrows (average initial body weight of 24.70 ± 0.09 kg) with a 2 × 3 factorial arrangement of treatments and main effects of diet type (corn-or wheat-soybean meal-based-diets) and enzyme supplementation (without, with Phy or with MCPC). Each group was designed with 6 replicate pens. The MCPC increased (p

Abstract Background Transmissible gastroenteritis virus (TGEV) is one of the main pathogens causing severe diarrhea of piglets. The pathogenesis of TGEV is closely related to intestinal inflammation. All-trans retinoic acid (ATRA) is the main active metabolite of vitamin A, which has immunomodulatory and anti-inflammatory properties. However, it is unclear whether ATRA can alleviate TGEV-induced intestinal inflammation and barrier dysfunction in piglets. This study aimed to investigate the effects of ATRA on growth performance, diarrhea, intestinal inflammation and intestinal barrier integrity of TGEV-challenged piglets. Methods In a 19-d study, 32 weaned piglets were randomly divided into 4 treatments: Control group (basal diet), TGEV group (basal diet + TGEV challenge), TGEV + ATRA5 group (basal diet + 5 mg/d ATRA + TGEV challenge) and TGEV + ATRA15 group (basal diet + 15 mg/d ATRA + TGEV challenge). On d 14, piglets were orally administered TGEV or the sterile medium. Results Feeding piglets with 5 and 15 mg/d ATRA alleviated the growth inhibition and diarrhea induced by TGEV (P

Abstract Background This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). Methods This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. Results A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. Conclusions Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. Trial Registration ISRCTN34355813. Registered on 25/01/2021.

Abstract Perylenequinones (PQs) from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy. However, the lower yield of PQ production in mycelium cultures is an important bottleneck for their clinical application. Light has long been recognized as a pivotal regulatory signal for fungal secondary metabolite biosynthesis. In this study, we explored the role of nitric oxide (NO) in the growth and PQ biosynthesis in mycelium cultures of Shiraia sp. S9 exposed to red light. The continuous irradiation with red light (627 nm, 200 lx) suppressed fungal conidiation, promoted hyphal branching, and elicited a notable increase in PQ accumulation. Red light exposure induced NO generation, peaking to 81.7 μmol/g FW on day 8 of the culture, with the involvement of nitric oxide synthase (NOS)- or nitrate reductase (NR)-dependent pathways. The application of a NO donor sodium nitroprusside (SNP) restored conidiation of Shiraia sp. S9 under red light and stimulated PQ production, which was mitigated upon the introduction of NO scavenger carboxy-PTIO or soluble guanylate cyclase inhibitor NS-2028. These results showed that red light-induced NO, as a signaling molecule, was involved in the regulation of growth and PQ production in Shiraia sp. S9 through the NO-cGMP-PKG signaling pathway. While mycelial H2O2 content exhibited no significant alternations, a transient increase of intracellular Ca2+ and extracellular ATP (eATP) content was detected upon exposure to red light. The generation of NO was found to be interdependent on cytosolic Ca2+ and eATP concentration. These signal molecules cooperated synergistically to enhance membrane permeability and elevate the transcript levels of PQ biosynthetic genes in Shiraia sp. S9. Notably, the combined treatment of red light with 5 μM SNP yielded a synergistic effect, resulting in a substantially higher level of hypocrellin A (HA, 254 mg/L), about 3.0-fold over the dark control. Our findings provide valuable insights into the regulation of NO on fungal secondary metabolite biosynthesis and present a promising strategy involving the combined elicitation with SNP for enhanced production of photoactive PQs and other valuable secondary metabolites in fungi. Graphical Abstract

Introduction Accumulating studies have shown that copper has a detrimental effect in cells, and the cuproptosis-related gene signatures have been constructed as clinical tools to predict prognosis in tumors. However, the heterogeneity of cuproptosis has not been fully investigated in ischemic stroke. Material and methods Here, we combined the bulk RNA-seq and single cell-RNA-seq data for stroke to investigate the role of cuproptosis in stroke. Results We identified the cuproptosis-related differentially expressed genes (CuDEGs) in ischemic stroke. Then, we tried to find the hub genes with the machine learning method and WGCNA. We highlighted four genes identified by these methods and proposed a potential diagnostic model in ischemic stroke. Conclusions Our findings revealed cuproptosis-related hub genes, which could provide useful biomarkers in ischemic stroke.

Guigarra cailaoensis is a member of family Cyprinidae, subfamily Labeoninae (Cypriniformes) which was recently discovered in southwestern China. Following its initial description, additional information on this species has remained notably scarce. In the current study, we assemble the complete mitochondrial genome (mitogenome) of G. cailaoensis using the Illumina sequencing platform. The mitogenome is identified as a circular, double-stranded DNA sequence of 16,593 base pairs, encompassing 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and a putative control region. Maximum-likelihood and Bayesian-inference approaches were used to construct phylogenetic trees for three datasets: (i) PCG sequences of the complete mitogenome (dataset 1); (ii) PCG sequences of the complete mitogenome combined with nuclear DNA (ncDNA) (Rag1) sequence (dataset 2); and (iii) ncDNA (Rag1) sequences (dataset 3). Phylogenetic analyses position G. cailaoensis as a sister taxon to the lineage consisting of Paraqianlabeo lineatus Zhao, Sullivan, Zhang & Peng, 2014 and Pseudogyrinocheilus prochilus Fang, 1933 in dataset 1, and to Pseudogyrinocheilus prochilus in dataset 2, species lacking an oral disc on the lower lip. However, G. cailaoensis showed a close relationship to the lineage consisting of Discogobio and Discocheilus in dataset 3, species possessing an oral disc on the lower lip. Nonetheless, a variety of species with an oral disc on the lower lip are clustered into different lineages across the three datasets that may indicate that the development of the oral disc is homoplastic within the subfamily Labeoninae. The outcomes of this study have the potential to support conservation efforts for this species and to enrich our understanding of genetic resources in the area.

Abstract Gankyrin is found in high levels in triple-negative breast cancer (TNBC) and has been established to form a complex with the E3 ubiquitin ligase MDM2 and p53, resulting in the degradation of p53 in hepatocarcinoma cells. Therefore, this study sought to determine whether gankyrin could inhibit ferroptosis through this mechanism in TNBC cells. The expression of gankyrin was investigated in relation to the prognosis of TNBC using bioinformatics. Co-immunoprecipitation and GST pull-down assays were then conducted to determine the presence of a gankyrin and MDM2 complex. RT-qPCR and immunoblotting were used to examine molecules related to ferroptosis, such as gankyrin, p53, MDM2, SLC7A11, and GPX4. Additionally, cell death was evaluated using flow cytometry detection of 7-AAD and a lactate dehydrogenase release assay, as well as lipid peroxide C11-BODIPY. Results showed that the expression of gankyrin is significantly higher in TNBC tissues and cell lines, and is associated with a poor prognosis for patients. Subsequent studies revealed that inhibiting gankyrin activity triggered ferroptosis in TNBC cells. Additionally, silencing gankyrin caused an increase in the expression of the p53 protein, without altering its mRNA expression. Co-immunoprecipitation and GST pull-down experiments indicated that gankyrin and MDM2 form a complex. In mouse embryonic fibroblasts lacking both MDM2 and p53, this gankyrin/MDM2 complex was observed to ubiquitinate p53, thus raising the expression of molecules inhibited by ferroptosis, such as SLC7A11 and GPX4. Furthermore, silencing gankyrin in TNBC cells disrupted the formation of the gankyrin/MDM2 complex, hindered the degradation of p53, increased SLC7A11 expression, impeded cysteine uptake, and decreased GPX4 production. Our findings suggest that TNBC cells are able to prevent cell ferroptosis through the gankyrin/p53/SLC7A11/GPX4 signaling pathway, indicating that gankyrin may be a useful biomarker for predicting TNBC prognosis or a potential therapeutic target.

To explore the effects of fermented rapeseed meal (FRSM) on growth performance and intestinal health, a total of 30 growing pigs were randomly allotted to three treatments consisting of corn-soybean meal diet (CSD), rapeseed meal diet (RSD), and fermented rapeseed meal diet (FRSD). Results showed that compared with RSD, FRSD feeding increased the average daily gain and final body weight in pigs (P

Baoshan is a world-class skarn Cu-polymetallic deposit located at the junction of the Nanling and Qin-Hang metallogenic belts in China. While there has been extensive research on the mineralogy and geochemistry of skarn deposits, studies on the fluid characteristics and evolutionary history from the early to late skarn stages in such deposits are still limited. In this study, we analyzed garnet and pyroxene from the early skarn stage and scheelite from the late skarn stage of the Baoshan deposit. We distinguished two generations of garnet (Grt1 and Grt2), one generation of pyroxene, and three generations of scheelite (Sch I, Sch II, and Sch III) on the basis of mineral assemblages and microscopic characteristics. Grt1 appears coarse-grained, and Grt2 cuts through Grt1 as veinlets. In Grt1, the andradite end-member increases from the core to the rim, while the grossular portion decreases (Ad35–36Gr59–61Sp3–4 to Ad59–61Gr36–37Sp2–3), and in Grt2, the andradite end-member significantly increases (Ad41–73Gr25–55Sp2–3). Grt1 and Grt2 have similar trace element compositions, with enrichment in Zr and depletion in Nb and Hf, depletion in LREE, enrichment in HREE, and weak negative Eu anomalies. Pyroxene coexists with Grt1 and is similarly cut by Grt2, with its composition mainly being diopside (Di82–99Hd0.6–15Jo0–3.2). Sch I and Sch II appear as anhedral to subhedral grains, while Sch III is predominantly found in veinlets. In Sch I and Sch II, most REEs enter the scheelite lattice via the Na-REE coupled substitution mechanism, with a smaller portion substituting Ca vacancies. In Sch III, the substitution mechanism involving Ca site vacancies may dominate. During the early skarn stage, the oxygen fugacity of the fluid gradually decreased from Grt1 and pyroxene to Grt2. In the late skarn stage, fluid oxygen fugacity remains stable from Sch I and Sch II to Sch III in shallow parts but significantly decreases in deeper parts. The garnet and pyroxene from the Baoshan deposit align with typical skarn Cu deposit compositions, while scheelite in the late skarn stage shows Sch I, Sch II, and shallow Sch III as skarn-type and deep Sch III as vein-type scheelite. Early skarn stage fluids were weakly acidic. Sch I, Sch II, and Sch III originated from fluids related to the Baoshan granite porphyry, with Sch III also showing evidence of water–rock interaction. This study reconstructed the fluid evolution history from the early to late skarn stages at the Baoshan deposit, providing insights into the ore-forming processes of other skarn deposits.

Meconopsis integrifolia is an endangered Tibetan medicinal plant with significant medicinal and ornamental value. Understanding its genetic diversity and structure is crucial for its sustainable utilization and effective conservation. Here, we develop a set of SSR markers based on transcriptome data to analyze the genetic diversity and structure of 185 individuals from 16 populations of M. integrifolia. The results indicate that M. integrifolia exhibits relatively high genetic diversity at the species level (the percentage of polymorphic bands PPB = 91.67%, Nei’s genetic diversity index He = 0.2989, Shannon’s information index I = 0.4514) but limited genetic variation within populations (PPB = 12.08%, He = 0.0399, I = 0.0610). The genetic differentiation among populations is relatively high (the coefficient of gene differentiation GST = 0.6902), and AMOVA analysis indicates that 63.39% of the total variation occurs among populations. This suggests that maintaining a limited number of populations is insufficient to preserve the overall diversity of M. integrifolia. Different populations are categorized into four representative subclusters, but they do not cluster strictly according to geographical distribution. Limited gene flow (Nm = 0.2244) is likely the main reason for the high differentiation among these populations. Limited seed and pollen dispersal abilities, along with habitat fragmentation, may explain the restricted gene flow among populations, highlighting the necessity of conserving as many populations in the wild as possible.

Intrauterine growth retardation (IUGR) in piglets is associated with a high rate of morbidity and mortality after birth due to gut dysfunction, and the underlying mechanisms remain poorly understood. This study selected six pairs of IUGR newborn male piglets and normal birth weight newborn piglets (Large White × Landrace) to investigate differences in intestinal structure and digestive functions, intestinal ERS and apoptosis, intestinal barrier function, and inflammatory response. The results showed that IUGR significantly reduced the jejunal villi height (p < 0.05) and the ratio of villus-height-to-crypt-depth (p = 0.05) in neonatal piglets. Additionally, the microvilli in the jejunum of IUGR neonatal piglets were shorter than those in normal-weight piglets, and swelling of the mitochondria and expansion of the endoplasmic reticulum were observed. IUGR also significantly reduced serum glucose and lactase levels (p < 0.05) while significantly increasing mRNA levels of jejunal IRE1α, EIF2α, CHOP, Bax, Caspase9, Mucin2, Claudin-1, Occludin, ZO-1, Bcl-2, IL-6, and IFN-γ (p < 0.05), as well as GRP78 protein levels in neonatal piglets (p < 0.05). These findings suggest that IUGR impairs intestinal structure and barrier function in newborn piglets by enhancing intestinal inflammatory responses, activating intestinal ERS and the signaling pathways related to the unfolded protein response, thereby inducing ERS-related apoptosis.

Tendons serve as important weight-bearing structures that smoothly transfer forces from muscles to skeletal parts, allowing contracted muscle movements to be translated into corresponding joint movements. For body mechanics, tendon tissue plays an important role. If the tendons are damaged to varying degrees, it can lead to disability or pain in patients. That is to say, tendon injuries havea significant impact on quality of life and deserve our high attention. Compared to other musculoskeletal tissues, tendons are hypovascular and hypo-cellular, and therefore have a greater ability to heal, this will lead to a longer recovery period after injury or even disability, which will significantly affect the quality of life. There are many causes of tendon injury, including trauma, genetic factors, inflammation, aging, and long-term overuse, and the study of related mechanisms is of great significance. Currently, tendon there are different treatment modalities, like injection therapy and surgical interventions. However, they have a high failure rate due to different reasons, among which the formation of adhesions severely weakens the tissue strength, affecting the functional recovery and the patient’s quality of life. A large amount of data has shown that non coding RNAs can play a huge role in this field, thus attracting widespread attention from researchers from various countries. This review summarizes the relevant research progress on non-coding RNAs in tendon injuries, providing new ideas for a deeper understanding of tendon injuries and exploring new diagnostic and therapeutic approaches.

Methane metabolism, driven by methanogenic and methanotrophic microorganisms, plays a pivotal role in the carbon cycle. As seawater intrusion and soil salinization rise due to global environmental shifts, understanding how salinity affects methane emissions, especially in deep strata, becomes imperative. Yet, insights into stratigraphic methane release under varying salinity conditions remain sparse. Here we investigate the effects of salinity on methane metabolism across terrestrial and coastal strata (15–40 m depth) through in situ and microcosm simulation studies. Coastal strata, exhibiting a salinity level five times greater than terrestrial strata, manifested a 12.05% decrease in total methane production, but a staggering 687.34% surge in methane oxidation, culminating in 146.31% diminished methane emissions. Salinity emerged as a significant factor shaping the methane-metabolizing microbial community's dynamics, impacting the methanogenic archaeal, methanotrophic archaeal, and methanotrophic bacterial communities by 16.53%, 27.25%, and 22.94%, respectively. Furthermore, microbial interactions influenced strata system methane metabolism. Metabolic pathway analyses suggested Atribacteria JS1's potential role in organic matter decomposition, facilitating methane production via Methanofastidiosales. This study thus offers a comprehensive lens to comprehend stratigraphic methane emission dynamics and the overarching factors modulating them.

The incidence of emergence delirium (ED) is higher in preschool children undergoing tonsillectomy and/or adenoidectomy. The purpose of this study was to determine the median effective dose (ED50) of dexmedetomidine (DEX) for the inhibition of ED in preschool children by using probit regression analysis. A total of 140 anesthesia records were retrieved and divided into seven groups based on the infusion rate of DEX: .2, .25, .3, .35, .4, .45, and .5 μg·kg −1 ·h −1 . The Pediatric Anesthesia Emergence Delirium Scale (PAEDS) was used to assess ED in preschool children, and ED was defined as a PAEDS score ≥ 10. Probit regression analysis revealed that the ED50 and ED95 of DEX were .31 μg·kg −1 ·h −1 (95% CI: .29–.35) and .48 μg·kg −1 ·h −1 (95% CI: .44–.56), respectively. Probit(p) = −2.84 + 9.28 × ln (Dose), (χ 2 = 1.925, P = .859). The PAEDS score was significantly increased in the ED group, and the rate of bradycardia was significantly decreased in the ED group compared with the without ED group (27.3% vs 54.1%, P = .02). DEX can effectively inhibit the ED in preschool children undergoing tonsillectomy and/or adenoidectomy, however, bradycardia was the main complication.

Virulence factors (VFs) are key factors for microorganisms to establish defense mechanisms in the host and enhance their pathogenic potential. However, the spectrum of virulence factors in pig colon and feces, as well as the influence of dietary and genetic factors on them, remains unreported. In this study, we firstly revealed the diversity, abundance and distribution characteristics of VFs in the colonic contents of different breeds of pigs (Taoyuan, Xiangcun and Duroc pig) fed with different fiber levels by using a metagenomic analysis. The analysis resulted in the identification of 1,236 virulence factors, which could be grouped into 16 virulence features. Among these, Taoyuan pigs exhibited significantly higher levels of virulence factors compared to Duroc pigs. The high-fiber diet significantly reduced the abundance of certain virulence factor categories, including iron uptake systems (FbpABC, HitABC) and Ig protease categories in the colon, along with a noteworthy decrease in the relative abundance of plasmid categories in mobile genetic elements (MGEs). Further we examined VFs in feces using absolute quantification. The results showed that high-fiber diets reduce fecal excretion of VFs and that this effect is strongly influenced by MGEs and short-chain fatty acids (SCFAs). In vitro fermentation experiments confirmed that acetic acid (AA) led to a decrease in the relative abundance of VFs (p

Summary: Both therapeutic hypothermia and neural stem cells (NSCs) transplantation have shown promise in neuroprotection and neural repair after brain injury. However, the effects of therapeutic hypothermia on neuronal differentiation of NSCs are not elucidated. In this study, we aimed to investigate whether mild hypothermia promoted neuronal differentiation in cultured and transplanted human NSCs (hNSCs). A significant increase in neuronal differentiation rate of hNSCs was found when exposed to 35°C, from 33% to 45% in vitro and from 7% to 15% in vivo. Additionally, single-cell RNA sequencing identified upregulation of RNA-binding motif protein 3 (RBM3) in neuroblast at 35°C, which stabilized the SRY-box transcription factor 11 (SOX11) mRNA and increased its protein expression, leading to an increase in neuronal differentiation of hNSCs. In conclusion, our study highlights that mild hypothermia at 35°C enhances hNSCs-induced neurogenesis through the novel RBM3-SOX11 signaling pathway, and provides a potential treatment strategy in brain disorders.

Background: Trans-spinal electrical stimulation (tsES) to the intact spinal cord poststroke may modulate the cortico-muscular control in stroke survivors with diverse lesions in the brain. This work aimed to investigate the immediate effects of tsES on the cortico-muscular descending patterns during voluntary upper extremity (UE) muscle contractions by analyzing cortico-muscular coherence (CMCoh) and electromyography (EMG) in people with chronic stroke.Methods: Twelve chronic stroke participants were recruited to perform wrist-hand extension and flexion tasks at submaximal levels of voluntary contraction for the corresponding agonist flexors and extensors. During the tasks, the tsES was delivered to the cervical spinal cord with rectangular biphasic pulses. Electroencephalography (EEG) data were collected from the sensorimotor cortex, and the EMG data were recorded from both distal and proximal UE muscles. The CMCoh, laterality index (LI) of the peak CMCoh, and EMG activation level parameters under both non-tsES and tsES conditions were compared to evaluate the immediate effects of tsES on the cortico-muscular descending pathway.Results: The CMCoh and LI of peak CMCoh in the agonist distal muscles showed significant increases (p < 0.05) during the wrist-hand extension and flexion tasks with the application of tsES. The EMG activation levels of the antagonist distal muscle during wrist-hand extension were significantly decreased (p < 0.05) with tsES. Additionally, the proximal UE muscles exhibited significant decreases (p < 0.05) in peak CMCoh and EMG activation levels by applying tsES. There was a significant increase (p < 0.05) in LI of peak CMCoh of proximal UE muscles during tsES.Conclusion: The cervical spinal cord neuromodulation via tsES enhanced the residual descending excitatory control, activated the local inhibitory circuits within the spinal cord, and reduced the cortical and proximal muscular compensatory effects. These results suggested the potential of tsES as a supplementary input for improving UE motor functions in stroke rehabilitation.

Watermelon is an important horticultural plant. A bibliometric analysis of the watermelon literature was carried out in order to analyze the research state, hotspots, and trends, as well as to highlight the overall watermelon research development from a holistic viewpoint. The summary of watermelon research is given via metrological analysis based on a set of indices using a newly built Bibliometrix R-package tool. This study gathered 6,632 documents indexed in the Core Collection of Web of Science (WoS) in the domain of watermelon from 1992 to 2022 using bibliometrix. The results indicated that the number of published articles showed an apparently upward trend. The United States was in the first place, with Plant Disease being the most productive journal. Levi A from the United States Department of Agriculture-Agricultural Research Service is the most prolific author, and Levi A is the most cited; The most frequently used keywords by authors are ''growth'', ''resistance'', ''identification'', ''yield'', ''quality'' ''plants'', ''watermelon stomach'' and ''expression''; The most talked-about issues in this subject are resistance, yield, and quality, which highlight the crucial research areas. To effectively comprehend the turning moments for future research, it is useful to monitor the hotspots and frontiers of watermelon studies. The results highlight the future paths for study in the field of watermelon and provide useful information for researchers interested in the topic.

Introduction and Objectives: Cholangiocarcinoma (CCA) is characterized by early distant invasion and metastasis, whereas the underlying mechanism is still obscure. Increasing evidence shows that collagen type Ι alpha 1 (COL1A1) is a gene associated with the progression of multiple diseases. Here, we attempted to investigate the role of COL1A1 in CCA. Materials and Methods: The expression of COL1A1 between tumor tissues and adjacent normal tissues obtained from CCA patients was detected by Western blot and immunofluorescence, followed by analysis of its clinical significance. Then, the biological effects of COL1A1 overexpression or knockdown on CCA cells were evaluated in vitro and in vivo. Finally, molecular mechanism of COL1A1 in regulating the invasion and metastasis of CCA cells was determined by a series of experiments. Results: COL1A1 expression was significantly higher in CCA pathological tissues than in corresponding adjacent normal tissues. Analysis of 83 CCA patients showed that higher expression of COL1A1 was correlated with poorer patient prognosis. Notably, overexpression or knockdown experiments revealed that COL1A1 contributed to the migration and invasion, as well as epithelial-to-mesenchymal transition (EMT), in CCA cells. Further investigations demonstrated that matrix metalloproteinase-2 (MMP2) promoted COL1A1 upregulation via the integrin alpha Ⅴ pathway, therefore affecting ECM remodelling and inducing EMT in CCA cells. Moreover, COL1A1 expression was positively related to PD-1 and PD-L1 in CCA, and COL1A1 increased PD-L1 expression by activating the NF-κB pathway. Conclusions: COL1A1 plays an important role in regulating CCA progression and may act as a promising biomarker and therapeutic target for CCA.

Abstract Magnetic‐geared double‐rotor machines are recognized as a promising power‐splitting component in hybrid electric aircrafts (HEAs). However, the high fuel efficiency speed of the turbine engine in HEAs is about 10,000 rpm, whereas conventional topologies suffer from low efficiency at high speed due to its specific operation principle—the magnetic field modulating principle. A coreless stator magnetic‐geared double‐rotor machine (CS‐MGDRM) is proposed to enhance high‐speed efficiency and thus comply with the operation condition of HEAs. First, the machine structure and hybrid propulsion system configuration are introduced, and power‐flow analysis of three basic operation modes is presented. Second, the operation principle of the machine is illustrated, and investigation of electromagnetic performances is carried out by finite element analysis. Third, an analytical model of the machine is developed, based on which the design optimization towards the maximum torque capacity is investigated. Furthermore, the loss distribution law and transmission efficiency are analysed and compared with conventional scheme, and the power factor characteristic is investigated as well. Finally, the overall performance of the proposed machine is evaluated.

Abstract Background In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. Objectives To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. Methods We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. Results The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. Interpretation LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

Abstract Background Novel endoscopic techniques used in the treatment of gastric lesions with local submucosal fibrosis need preclinical evaluation and training due to safety limitations. Therefore, the purpose of our study was to establish an animal model of gastric local fibrotic target lesions and assess its feasibility in the evaluation and training of endoscopic techniques. Methods In six experimental beagles, a 50% glucose solution was injected into three submucosal areas of the fundus, body, and antrum of the stomach to create gastric local fibrotic target lesions (experimental group). On post-injection day (PID) 7, the injection sites were assessed endoscopically to confirm the presence of submucosal fibrosis formation, and the dental floss clip traction assisted endoscopic submucosal dissection (DFC-ESD) procedure was performed on the gastric local fibrotic target lesions to confirm its feasibility after endoscopic observation. The normal gastric mucosa of six control beagles underwent the same procedure (control group). All the resected specimens were evaluated by histological examination. Results All 12 beagles survived without postoperative adverse events. On PID 7, 16 ulcer changes were observed at the injection sites (16/18) under the endoscope, and endoscopic ultrasonography confirmed the local submucosal fibrosis formation in all ulcer lesions. The subsequent DFC-ESD was successfully performed on the 32 gastric target lesions, and the mean submucosal dissection time in the ulcer lesions was greater than that in the normal gastric mucosa (15.3 ± 5.6 vs. 6.8 ± 0.8 min; P

Introduction To investigate shared gene signatures between COVID-19 and ischemic stroke. Material and methods Combining the existing bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) data for COVID-19 to obtain a more comprehensive understanding of the role of dysregulated metabolism. Results A total of 19 up-regulated differentially expressed genes (DEGs) and 24 down-regulated genes were selected for subsequent analyses. Nine genes were finally identified with the machine learning method as a potential diagnostic model in both ischemic stroke and COVID-19. In addition, the hub genes were related to both immune infiltration and metabolic pathways. Conclusions Our study revealed the common molecular profile of COVID-19 and ischemic stroke.

Abstract The contra‐rotating machine (CRM) has been a preferable selection of the contra‐rotating propulsion system (CRPS) owing to its high efficiency, high compactness, and low noise. However, the conventional CRM with rotating stator has the problem of brush and slip ring, and the conventional brushless CRM has the problem of coordinated control of equal and opposite torque. Aiming at the above problems, this article proposes a transverse‐dislocated magnetic‐field modulated brushless contra‐rotating machine (TDMFM‐BCRM). The proposed TDMFM‐BCRM has some advantages of no rotating winding, no associated brushes and slip rings, and equal and opposite torques at any time, therefore it has good potential for the CRPS. The working principle of the TDMFM‐BCRM including three dimensional magnetic‐field modulated theory, back electromotive force (EMF) generation, and torque relation is studied. Then, the influences of main parameters including magnetic block parameters and PM sizes on torques are investigated. The critical electromagnetic performances of the TDMFM‐BCRM are analysed. A prototype of TDMFM‐BCRM is manufactured and measured to validate the above analysis. Finally, the comparison of the TDMFM‐BCRM and the existing schemes are analysed.