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We investigate the Sturm-Liouville (S-L) operator with boundary and transfer conditions dependent on the eigen-parameter. By utilizing interval partitioning and factorization techniques of characteristic function, it is proven that this problem has a finite number of eigenvalues when the coefficients of the equation meet certain conditions, and some conditions for determining the number of eigenvalues are provided. The results indicate that the number of eigenvalues in this problem varies when the transfer conditions depend on the eigen-parameter. Furthermore, the equivalence between this problem and matrix eigenvalue problems is studied, and an equivalent matrix representation of the S-L problem is presented.

Abstract Algin oligosaccharides have been applied in diverse industries and could be innovative synthesized by alginate-degrading bacteria. For enhance the alginate degradation efficiency to produce more algin oligosaccharides, a mutant strain (Cobetia sp. cqz5-12-M1) was obtained through the complex mutagenesis using UV and the alkylating agent 1-methyl-3-nitro-1-nitrosoguanidine. The enzyme activity of the fermentation supernatant of mutant exhibited a significant 38.09% (53.98 ± 0.69 U/mL) increase, and its optimal growth conditions were determined as: 5 g/L sodium alginate, 5 g/L yeast powder, 30 g/L NaCl, 2 g/L K2HPO4, 2 g/L KH2PO4, 1 g/L MgSO4•7H2O, 0.01 g/L FeSO4•7H2O, pH 6.5, and 34 ℃. Moreover, its optimal degradation conditions were identified as: 5 g/L sodium alginate, 5 g/L yeast powder, 30 g/L NaCl, 2 g/L K2HPO4, 2 g/L KH2PO4, 1 g/L MgSO4•7H2O, 0.01 g/L FeSO4•7H2O, pH 6.5, 31 ℃ and 72 h, yielding an enzyme activity of 120.98 ± 1.40 U/mL in the fermentation supernatant. Conclusive experiments on reagent tolerance revealed the growth of the mutant strain was significantly inhibited by 3% hydrogen peroxide, 5% carbolic acid, and 10 mg/mL gatifloxacin. Additionally, the alginate degradation capacity of mutant strain was highly significantly inhibited by 75% ethanol and all tested antibiotics.

Abstract The existing diagnostic methods of epilepsy have great limitations, and more reliable and less difficult diagnostic methods are needed. We collected serum samples of adult patients with first-diagnosed epilepsy (EPs) and seizure control patients (EPRs) for non-targeted metabolomics detection and found that they were both significantly altered, with increased expression of nicotine addiction, linoleic acid metabolism, purine metabolism, and other metabolic pathways. The diagnostic model based on 4 differential metabolites achieved a diagnostic efficiency of 99.4% in the training cohort and 100% in the validation cohort. In addition, the association analysis of oral flora, serum metabolism, and clinical indicators also provided a new angle to analyze the mechanism of epilepsy. In conclusion, this study characterized the serum metabolic characteristics of EPs and EPRs and the changes before and after epilepsy control based on a large cohort, demonstrating the potential of metabolites as non-invasive diagnostic tools for epilepsy.

Abstract Background The plasma metabolome reflects the physiological state of various biological processes and can serve as a proxy for disease risk. Plasma metabolite variation, influenced by genetic and epigenetic mechanisms, can also affect the cellular microenvironment and blood cell epigenetics. The interplay between the plasma metabolome and the blood cell epigenome remains elusive. In this study, we performed an epigenome-wide association study (EWAS) of 1183 plasma metabolites in 693 participants from the LifeLines-DEEP cohort and investigated the causal relationships in DNA methylation–metabolite associations using bidirectional Mendelian randomization and mediation analysis. Results After rigorously adjusting for potential confounders, including genetics, we identified five robust associations between two plasma metabolites (l-serine and glycine) and three CpG sites located in two independent genomic regions (cg14476101 and cg16246545 in PHGDH and cg02711608 in SLC1A5) at a false discovery rate of less than 0.05. Further analysis revealed a complex bidirectional relationship between plasma glycine/serine levels and DNA methylation. Moreover, we observed a strong mediating role of DNA methylation in the effect of glycine/serine on the expression of their metabolism/transport genes, with the proportion of the mediated effect ranging from 11.8 to 54.3%. This result was also replicated in an independent population-based cohort, the Rotterdam Study. To validate our findings, we conducted in vitro cell studies which confirmed the mediating role of DNA methylation in the regulation of PHGDH gene expression. Conclusions Our findings reveal a potential feedback mechanism in which glycine and serine regulate gene expression through DNA methylation.

Abstract Quantum secret sharing is a basic quantum cryptographic primitive, which has a lot of applications in information security and privacy preservation. An efficient multiparty quantum secret sharing protocol (Kuo et al. in EPJ Quantum Technol 10(1):29, 2023) based on a novel structure and single qubits was reported recently. In this paper, we give a cryptanalysis of this protocol and show that it cannot satisfy the security requirement for secret sharing because an unauthorized set of agents can gain access to some information on the dealer’s secret by a special collusion attack. Furthermore, we put forward a way to deal with the security problem.

Tyrosine phosphorylation is crucial for controlling normal cell growth, survival, intercellular communication, gene transcription, immune responses, and other processes. protein tyrosine phosphatase (PTP) and protein tyrosine kinases (PTK) can achieve this goal by regulating multiple signaling pathways. Oedaleus decorus asiaticus is an important pest that infests the Mongolian Plateau grassland. We aimed to evaluate the survival rate, growth rate, overall performance, and ovarian developmental morphology of the 4th instar nymphs of O. decorus asiaticus while inhibiting the activity of protein tyrosine phosphatase-1B (PTP1B) and PTK. In addition, the expression and protein phosphorylation levels of key genes in the MAPK signaling pathway and antioxidant enzyme activity were assessed. The results showed no significant differences in survival rate, growth rate, or overall performance between PTP1B inhibitor treatment and control. However, after PTK inhibitor treatment, these indexes were significantly lower than those in the control. The ovarian size of female larvae after 15 days of treatment with PTK inhibitors showed significantly slower development, while female larvae treated with PTP1B exhibited faster ovarian growth than the control group. In comparison to controls and nymphs treated with PTK inhibitors, the expression and phosphorylation levels of key genes in the MAPK signaling pathway under PTP1B inhibitor treatments were significantly higher in 4th instar nymphs. However, reactiveoxygen (ROS) species levels and the activities of NADPH oxidase and other antioxidant enzymes were considerably reduced, although they were significantly greater in the PTK inhibitor treatment. The results suggest that PTP1B and PTK feedback inhibition in the mitogen-activated-protein kinases (MAPK) signal transfer can regulate the physiological metabolism of the insect as well as its developmental rate. These findings can facilitate future uses of PTP1B and PTK inhibitors in controlling insect development to help control pest populations.

Abstract Pancreatic cancer (PC) is one of the most common malignant tumors of the digestive tract and has a very high mortality rate worldwide. Different PC patients may respond differently to therapy and develop therapeutic resistance due to the complexity and variety of the tumor microenvironment. The Eph/ephrin signaling pathway is extensively involved in tumor-related biological functions. However, the key function of the Eph/ephrin signaling pathway in PC has not been fully elucidated. We first explored a pan-cancer overview of Eph/ephrin signaling pathway genes (EPGs). Then we grouped the PC patients into 3 subgroups based on EPG expression levels. Significantly different prognoses and tumor immune microenvironments between different subtypes further validate Eph/ephrin's important role in the pathophysiology of PC. Additionally, we estimated the IC50 values for several commonly used molecularly targeted drugs used to treat PC in the three clusters, which could help patients receive a more personalized treatment plan. Following a progressive screening of optimal genes, we established a prognostic signature and validated it in internal and external test sets. The receiver operating characteristic (ROC) curves of our model exhibited great predictive performance. Meanwhile, we further validated the results through qRT-PCR and immunohistochemistry. Overall, this research provides fresh clues on the prognosis and therapy of PC as well as the theoretical groundwork for future Eph/ephrin signaling pathway research.

Abstract Surface passivation, a desirable natural consequence during initial oxidation of alloys, is the foundation for functioning of corrosion and oxidation resistant alloys ranging from industrial stainless steel to kitchen utensils. This initial oxidation has been long perceived to vary with crystal facet, however, the underlying mechanism remains elusive. Here, using in situ environmental transmission electron microscopy, we gain atomic details on crystal facet dependent initial oxidation behavior in a model Ni-5Cr alloy. We find the (001) surface shows higher initial oxidation resistance as compared to the (111) surface. We reveal the crystal facet dependent oxidation is related to an interfacial atomic sieving effect, wherein the oxide/metal interface selectively promotes diffusion of certain atomic species. Density functional theory calculations rationalize the oxygen diffusion across Ni(111)/NiO(111) interface, as contrasted with Ni(001)/NiO(111), is enhanced. We unveil that crystal facet with initial fast oxidation rate could conversely switch to a slow steady state oxidation.

Abstract The regulatory significance of ubiquitin-specific peptidase 32 (USP32) in tumor is significant, nevertheless, the biological roles and regulatory mechanisms of USP32 in non-small cell lung cancer (NSCLC) remain unclear. According to our research, USP32 was strongly expressed in NSCLC cell lines and tissues and was linked to a bad prognosis for NSCLC patients. Interference with USP32 resulted in a significant inhibition of NSCLC cell proliferation, migration potential, and EMT development; on the other hand, USP32 overexpression had the opposite effect. To further elucidate the mechanism of action of USP32 in NSCLC, we screened H1299 cells for interacting proteins and found that USP32 interacts with BAG3 (Bcl2-associated athanogene 3) and deubiquitinates and stabilizes BAG3 in a deubiquitinating activity-dependent manner. Functionally, restoration of BAG3 expression abrogated the antitumor effects of USP32 silencing. Furthermore, USP32 increased the phosphorylation level of the RAF/MEK/ERK signaling pathway in NSCLC cells by stabilizing BAG3. In summary, these findings imply that USP32 is critical to the development of NSCLC and could offer a theoretical framework for the clinical diagnosis and management of NSCLC patients in the future.

Abstract Polysaccharides are widely used as quality improvers for meat products. However, the mechanisms of how different ionic polysaccharides regulate the gelling properties of myofibrillar protein (MP) are still unclear. This study aimed to elucidate the contribution of different ionic polysaccharides to MP gelation and its mechanism. The enhancement of hydrogen bond, hydrophobic interaction, and disulfide bond between carboxymethyl cellulose sodium (CMC‐Na, anionic polysaccharide) and MP made them bind tightly, which contributes to the improvement of gel strength, water‐holding capacity, and viscoelasticity. Konjac glucomannan (neutral polysaccharide) mainly relied on physical filling to support the gel network and improve the gel characteristics. The electrostatic attraction between cationic polysaccharides and MP enhanced the binding between them. However, due to the large structure of chitosan (cationic polysaccharide) sugar chain, it can only attach to the surface of protein, which limits the interaction between them. These findings will provide guidance for the application of polysaccharides as food quality improvers or fat substitutes and the design of new low‐fat restructured meat products.

Background: Cannabidiol (CBD), extracted from Cannabis sativa, has anticancer, anti-inflammation, and analgesic effects. Nevertheless, its therapeutic effect and the mechanism by which it alleviates oral mucositis (OM) remain unclear. Aims: To explore the impact of CBD on OM in mice and on human oral keratinocyte (HOK) cells. Study Design: Expiremental study. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, GeneCard, DisGeNET, and Gene Expression Omnibus databases were used to conduct therapeutic target gene screening for drugs against OM. Cytoscape software was used to build networks linking components, targets, and diseases. The STRING database facilitated analysis of intertarget action relationships, and the target genes were analyzed for Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Occurrence of serum inflammation-related factors, hematoxylin and eosin staining, and immunohistochemistry were used to assess OM injury. Cell proliferation, migration, pyroptosis, and apoptosis of HOK cells under different treatments were assessed. Molecular mechanisms were elucidated through western blot and quantitative real-time polymerase chain reaction analyses. Results: A total of 49 overlapping genes were pinpointed as potential targets, with NF-κB1, PIK3R1, NF-κBIA, and AKT1 being recognized as hub genes among them. Additionally, the PI3K/Akt/NF-κB and interleukin-17 signaling pathways were identified as relevant. Our in vivo experiments showed that CBD significantly reduced the proportion of lesion area, mitigated oral mucosal tissue lesions, and downregulated the expression levels of genes and levels of proteins, including NLRP3, P65, AKT, and PI3K. In vitro experiments indicated that CBD enhanced HOK cell proliferation and migration and reduced apoptosis through inhibition of the PI3K/Akt/NF-κB signaling pathway and pyroptosis. Conclusion: Our findings suggest a novel mechanism for controlling OM, in which CBD suppresses the PI3K/Akt/NF-κB signaling pathway and pyroptosis, thereby mitigating OM symptoms.

Abstract Objective Pulmonary papillary adenoma is an extremely rare benign tumor. It is derived from type II lung cells and club cells, suggesting that it may originate from stem cells with two-way differentiation. Only one case has been reported with FGFR2-IIIb overexpression. Methods Two cases of pulmonary papillary adenoma with available data on clinical features, histological morphology, immunophenotype and molecular characteristics were analyzed. Results Both tumors were well-circumscribed unencapsulated nodules composed of papillary structures with fibrovascular cores lined by a single layer of cuboidal or columnar epithelium without necrosis, nuclear atypia and mitoses, or invasion. But malignant transformation features include complex branching structures and significantly enlarged, irregular, and crowded malignant cells in one case. Immunohistochemistry showed that the tumor cells were strongly positive for TTF1, NapsinA, EMA and CK7 and negative for CEA and P63, with a low Ki-67 proliferation index. The EGFR somatic mutation exon19:c.2236_2256delinsATC (p.E746_S752delinsI) was found in one case by next-generation sequencing (NGS) technology. Conclusion Pulmonary papillary adenoma is very rare. Virtually all papillary adenomas are clinically silent and discovered incidentally. They are benign tumors, and resection is curative. An EGFR 19 exon deletion mutation in a patient with this tumor type was detected for the first time by NGS, and our results suggest that the malignant transformation of pulmonary papillary adenoma may be mediated by EGFR mutation.

Transdermal drug delivery (TDD) has gained clinical approval over several decades, with extensive research dedicated to novel drug and device development. Despite notable research progress, the market adoption of TDD devices has not met anticipated levels, with oral administration and injection remaining predominant delivery methods. To maximize the potential of TDD, we identify bottlenecks hindering its widespread clinical application and propose promising research avenues. We begin by analyzing stringent demands necessary to truly benefit patients, addressing significant challenges in biomechanics, nanomedicine, and flexible electronics. Subsequently, we delve into skin anatomy, enhancement strategies, nano-carriers, and their underlining mechanisms, highlighting the importance and framework of quantitative modeling. Based on these discussions, we highlight the core strength of TDD, such as automatic precise administration based on feedback and high delivery efficiencies, especially applicable to localized conditions (e.g., central nervous system diseases, tumors). Finally, we envision the future of intelligent TDD device and its operation scenario, aiming to steer research efforts toward faster translation of laboratory innovations into widely used products for sufferers.

Abstract Background The analysis of differentially expressed genes in muscle tissues of sheep at different ages is helpful to analyze the gene expression trends during muscle development. In this study, the longissimus dorsi muscle of pure breeding Hu sheep (H), Suffolk sheep and Hu sheep hybrid F1 generation (SH) and East Friesian and Hu sheep hybrid sheep (EHH) three strains of sheep born 2 days (B2) and 8 months (M8) was used as the research object, and transcriptome sequencing technology was used to identify the differentially expressed genes of sheep longissimus dorsi muscle in these two stages. Subsequently, GO and KEGG enrichment analysis were performed on the differential genes. Nine differentially expressed genes were randomly selected and their expression levels were verified by qRT-PCR. Results The results showed that 842, 1301 and 1137 differentially expressed genes were identified in H group, SH group and EHH group, respectively. Among them, 191 differential genes were enriched in these three strains, including pre-folding protein subunit 6 (PFDN6), DnaJ heat shock protein family member A4 (DNAJA4), myosin heavy chain 8 (MYH8) and so on. GO and KEGG enrichment analysis was performed on 191 differentially expressed genes shared by the three strains to determine common biological pathways. The results showed that the differentially expressed genes were significantly enriched in ribosomes, unfolded protein binding, FoxO signaling pathway, glycolysis / glycogen generation and glutathione signaling pathway that regulate muscle protein synthesis and energy metabolism. The results of qRT-PCR were consistent with transcriptome sequencing, which proved that the sequencing results were reliable. Conclusions Overall, this study revealed the important genes and signaling pathways related to sheep skeletal muscle development, and the result laid a foundation for further understanding the mechanism of sheep skeletal muscle development.

Abstract Objective To investigate whether simethicone expediates the remission of abdominal distension after laparoscopic cholecystectomy (LC). Methods This retrospective study involved LC patients who either received perioperative simethicone treatment or not. Propensity score matching (PSM) was employed to minimize bias. The primary endpoint was the remission rate of abdominal distension within 24 h after LC. Univariable and multivariable logistic regression analyses were conducted to identify independent risk factors affecting the early remission of abdominal distension after LC. Subsequently, a prediction model was established and validated. Results A total of 1,286 patients were divided into simethicone (n = 811) and non-simethicone groups (n = 475) as 2:1 PSM. The patients receiving simethicone had better remission rates of abdominal distension at both 24 h and 48 h after LC (49.2% vs. 34.7%, 83.9% vs. 74.8%, respectively), along with shorter time to the first flatus (14.6 ± 11.1 h vs. 17.2 ± 9.1 h, P

Abstract Background Craniopharyngiomas (CPs) are generally derived from the craniopharyngeal duct epithelium, accounting for 38% and 24.5% of mortality in pediatric and adult patients, respectively. At present, the widespread application of the endoscopic endonasal transsphenoidal approach (EEA) has led to controversy between the traditional microscopic transcranial approach (TCA) and EEA in relation to the surgical management of CPs. Object and method We performed a systematic review and meta-analysis comparing the complications, surgical outcomes, and endocrine functions of patients with CPs to provide evidence-based decision-making in their surgical management. Result Overall, 11 observational studies with 12,212 participants were included in the meta-analysis, in which five of them only included an adult population, three of them only included a child population, and the other three studies included a mixed population (adult and child). In pediatric patients, the EEA achieved a higher gross total resection (GTR) rate (odds ratio (OR) = 5.25, 95%CI: 1.21–22.74), lower recurrence rate (OR = 0.54, 95%CI: 0.31–0.94, p = 0.030), and less hypopituitarism (OR = 0.34, 95%CI: 0.12–0.97, p = 0.043). In adult patients, EEA significantly improved mortality (OR = 0.09, 95%CI: 0.06–0.15, p

Calystegia hederacea Wall. in Roxb. 1824 is a perennial herbaceous vine in the family Convolvulaceae and has several biological effects. Herein, we reported the first complete chloroplast genome of C. hederacea. The chloroplast genome sequence was 152,057 bp in length, comparing a large single-copy (LSC) region of 87,891 bp, a small single-copy (SSC) region of 19,866 bp, and a pair of inverted repeat (IR) regions of 22,150 bp. This sequenced chloroplast genome contained 126 predicted genes, including 81 protein-coding genes, 37 tRNA genes, and eight rRNA genes, and the total GC content of the chloroplast genome was 37.79%. Phylogenetic analysis revealed that C. hederacea was closely related to C. soldanella. The chloroplast genome presented in this study will enrich the genome information of the genus Calystegia and provide deeper insights into the evolution study of the family Convolvulaceae.

Abstract Objective To report the long-term re-intervention of patients with uterine fibroids after ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation and to analyse the influencing factors of re-intervention in patients in the NPVR ≥ 80% group. Materials and methods Patients with a single uterine fibroid who underwent USgHIFU at our hospital from January 2012 to December 2019 were enrolled. The patients were divided into four groups according to different nonperfusion volume ratio (NPVR). Kaplan–Meier survival curve was used to analyse long-term re-intervention in different NPVR groups, and Cox regression was used to analyse the influencing factors of re-intervention in the NPVR ≥ 80% group. Main results A total of 1,257 patients were enrolled, of whom 920 were successfully followed up. The median follow-up time was 88 months, and the median NPVR was 85.0%. The cumulative re-intervention rates at 1, 3, 5, 8 and 10 years after USgHIFU were 3.4%, 11.8%, 16.8%, 22.6% and 24.1%, respectively. The 10-year cumulative re-intervention rate was 37.3% in the NPVR

Abstract Blood orange (BO) is a rare red-fleshed sweet orange (SWO) with a high anthocyanin content and is associated with numerous health-related benefits. Here, we reported a high-quality chromosome-scale genome assembly for Neixiu (NX) BO, reaching 336.63 Mb in length with contig and scaffold N50 values of 30.6 Mb. Furthermore, 96% of the assembled sequences were successfully anchored to 9 pseudo-chromosomes. The genome assembly also revealed the presence of 37.87% transposon elements and 7.64% tandem repeats, and the annotation of 30,395 protein-coding genes. A high level of genome synteny was observed between BO and SWO, further supporting their genetic similarity. The speciation event that gave rise to the Citrus species predated the duplication event found within them. The genome-wide variation between NX and SWO was also compared. This first high-quality BO genome will serve as a fundamental basis for future studies on functional genomics and genome evolution.

Abstract Objective This study aimed to investigate the relationships between childhood maltreatment, shame, and self-esteem among juvenile female offenders and to explore the potential influencing factors on their criminal behavior. Methods Using a stratified cluster sampling method, 1,227 juvenile female offenders from 11 provinces in China were surveyed using the Childhood Trauma Questionnaire (CTQ), Self-Esteem Scale (SES), and a self-developed Shame Questionnaire for Juvenile Offenders. Data were analyzed using descriptive statistics, correlation analysis, chi-square tests, t-tests, and structural equation modeling with mediation analysis. Results (1) Childhood maltreatment have a significant potential influencing factors on criminal behavior; (2) Childhood maltreatment was positively correlated with self-esteem(β = 0.351, p

Background/Aims Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. Methods Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. Results The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. Conclusions For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.

Abstract This study explores the relationship between social withdrawal and problematic social media use among college students, with a focus on the mediating roles of alexithymia and negative body image. Using the University Student Social Withdrawal Questionnaire, Social Media Addiction Scale, Toronto Alexithymia Scale, and Negative Body Image Scale, 2582 college students (33.46% male, average age = 19.46 years, SD = 2.23) were surveyed. Social withdrawal, alexithymia, negative body image, and problematic social media use were significantly correlated with each other. Social withdrawal positively predicted problematic social media use, and both alexithymia and negative body image played a chain mediating role between social withdrawal and problematic social media use. The findings indicate that individual social withdrawal is associated with college students’ problematic use of social media. The results suggest that alexithymia and negative body image may mediate this association, highlighting a potential pathway through which social withdrawal influences social media use patterns.

Bread wheat (Triticum aestivum) is a staple food crop worldwide. The genetic dissection of important nutrient traits is essential for the biofortification of wheat to meet the nutritional needs of the world’s growing population. Here, 45,298 single-nucleotide polymorphisms (SNPs) from 55K chip arrays were used to genotype a panel of 768 wheat cultivars, and a total of 154 quantitative trait loci (QTLs) were detected for eight traits under three environments by genome-wide association study (GWAS). Three QTLs (qMn-3B.1, qFe-3B.4, and qSe-3B.1/qFe-3B.6) detected repetedly under different environments or traits were subjected to subsequent analyses based on linkage disequilibrium decay and the P-values of significant SNPs. Significant SNPs in the three QTL regions formed six haplotypes for qMn-3B.1, three haplotypes for qFe-3B.4, and three haplotypes for qSe-3B.1/qFe-3B.6. Phenotypic analysis revealed significant differences among haplotypes. These results indicated that the concentrations of several nutrient elements have been modified during the domestication of landraces to modern wheat. Based on the QTL regions, we identified 15 high-confidence genes, eight of which were stably expressed in different tissues and/or developmental stages. TraesCS3B02G046100 in qMn-3B.1 and TraesCS3B02G199500 in qSe-3B.1/qFe-3B.6 were both inferred to interact with metal ions according to the Gene Ontology (GO) analysis. TraesCS3B02G199000, which belongs to qSe-3B.1/qFe-3B.6, was determined to be a member of the WRKY gene family. Overall, this study provides several reliable QTLs that may significantly affect the concentrations of nutrient elements in wheat grain, and this information will facilitate the breeding of wheat cultivars with improved grain properties.

Abstract Background In the aftermath of the COVID-19 pandemic, there has been a surge in human metapneumovirus (HMPV) transmission, surpassing pre-epidemic levels. We aim to elucidate the clinical and epidemiological characteristics of HMPV infections in the post-COVID-19 pandemic era. Methods In this retrospective single-center study, participants diagnosed with laboratory confirmed HMPV infection through Targeted Next Generation Sequencing were included. The study encompassed individuals admitted to Henan Children's Hospital between April 29 and June 5, 2023. Demographic information, clinical records, and laboratory indicators were analyzed. Results Between April 29 and June 5, 2023, 96 pediatric patients were identified as infected with HMPV with a median age of 33.5 months (interquartile range, 12 ~ 48 months). The majority (87.5%) of infected children were under 5 years old. Notably, severe cases were statistically younger. Predominant symptoms included fever (81.3%) and cough (92.7%), with wheezing more prevalent in the severe group (56% vs 21.1%). Coinfection with other viruses was observed in 43 patients, with Epstein–Barr virus (EBV) (15.6%) or human rhinovirus A (HRV type A) (12.5%) being the most common. Human respiratory syncytial virus (HRSV) coinfection rate was significantly higher in the severe group (20% vs 1.4%). Bacterial coinfection occurred in 74 patients, with Haemophilus influenzae (Hin) and Streptococcus pneumoniae (SNP) being the most prevalent (52.1% and 41.7%, respectively). Severe patients demonstrated evidence of multi-organ damage. Noteworthy alterations included lower concentration of IL-12p70, decreased lymphocytes percentages, and elevated B lymphocyte percentages in severe cases, with statistical significance. Moreover, most laboratory indicators exhibited significant changes approximately 4 to 5 days after onset. Conclusions Our data systemically elucidated the clinical and epidemiological characteristics of pediatric patients with HMPV infection, which might be instructive to policy development for the prevention and control of HMPV infection and might provide important clues for future HMPV research endeavors.

Abstract Due to the ignoring of rich spatio-temporal and global contextual information with convolutional neural networks in features extraction, the traditional method is prone to tracking drift or even failure in complex scenario, especially for the tiny targets in aerial photography scenario. In this work, it proposes a transformer feature integration network (TFITrack) to obtain diverse and comprehensive target feature for the robust object tracking. Based on the typical transformer architecture, it optimizes encoder and decoder structure for aggregating discriminative spatio-temporal information and global context-awareness feature. Furthermore, the encoder introduces the similarity calculation layer and dual-attention module; the aim is to deepen the similarity between features and make corrections for channel and spatial dimensions, and feature representation is improved. Finally, with the introduction of the temporal context filtering layer, unimportant feature information is ignored adaptively, obtaining a balance between the parameters number reduction and stable performance. Experimental results show that the proposed tracking algorithm exhibits excellent tracking performance on seven benchmark datasets, especially on the aerial dataset UAV123, UAV20L, and UAV123@10fps, which presents the advantages of the novel method in dealing with fast motion and external interference.

Abstract With the improvements in mechanization levels, it is difficult for the traditional intercropping planting patterns to meet the needs of mechanization. In the traditional maize‒soybean intercropping, maize has a shading effect on soybean, which leads to a decrease in soybean photosynthetic capacity and stem bend resistance, resulting in severe lodging, which greatly affects soybean yield. In this study, we investigated the effects of three intercropping ratios (four rows of maize and four rows of soybean; four rows of maize and six rows of soybean; six rows of maize and six rows of soybean) and two planting patterns (narrow-wide row planting pattern of 80–50 cm and uniform-ridges planting pattern of 65 cm) on soybean canopy photosynthesis, stem bending resistance, cellulose, hemicellulose, lignin and related enzyme activities. Compared with the uniform-ridge planting pattern, the narrow-wide row planting pattern significantly increased the LAI, PAR, light transmittance and compound yield by 6.06%, 2.49%, 5.68% and 5.95%, respectively. The stem bending resistance and cellulose, hemicellulose, lignin and PAL, TAL and CAD activities were also significantly increased. Compared with those under the uniform-ridge planting pattern, these values increased by 7.74%, 3.04%, 8.42%, 9.76%, 7.39%, 10.54% and 8.73% respectively. Under the three intercropping ratios, the stem bending resistance, cellulose, hemicellulose, lignin content and PAL, TAL, and CAD activities in the M4S6 treatment were significantly greater than those in the M4S4 and M6S6 treatments. Compared with the M4S4 treatment, these variables increased by 12.05%, 11.09%, 21.56%, 11.91%, 18.46%, 16.1%, and 16.84%, respectively, and compared with the M6S6 treatment, they increased by 2.06%, 2.53%, 2.78%, 2.98%, 8.81%, 4.59%, and 4.36%, respectively. The D-M4S6 treatment significantly improved the lodging resistance of soybean and weakened the negative impact of intercropping on soybean yield. Therefore, based on the planting pattern of narrow-wide row maize‒soybean intercropping planting pattern, four rows of maize and six rows of soybean were more effective at improving the lodging resistance of soybean in the semiarid region of western China.

Abstract Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.

Abstract Objective To compare the survival discrimination of the TNM9th and 8th editions for localized and locally advanced anal squamous cell carcinoma (ASCC) treated nonsurgically and suggest a simple revised staging system with data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods Overall survival (OS) was the primary endpoint. Survival comparisons between the T and N stages and the different staging systems were performed using the Kaplan–Meier method and log‐rank test, followed by correlation analysis and variable importance analysis (VIA). Additionally, multivariate analysis was employed to identify significant predictors, which were further visualized using a nomogram. Finally, calibration curve, C‐index, and decision curve analysis (DCA) were applied to assess the performance of the different staging systems. Results A total of 5384 patients with ASCC were analyzed, revealing superior discrimination OS by the TNM9th edition compared to that by the TNM8th edition. Multivariate analysis identified the T and N stages as significant OS predictors (all p 0.05). Correlation analysis demonstrated an increased correlation for the T stage between the TNM8th and 9th editions (ρ value from 0.7 to 0.89), while the N stage correlation decreased (ρ value from 0.84 to 0.56). VIA and the prognostic nomogram highlighted the greater importance of the T stage over the N stage. Based on these findings, a new staging system was developed, and its clinical utility was confirmed through calibration curves, C‐index values (from 0.598 to 0.604), and DCAs. Conclusions Our new staging system exhibited slightly better prognostic value compared to the TNM9th staging systems for nonmetastatic ASCC and warrants further validation.

IntroductionThe trend of human migration to terrestrial high altitudes (HA) has been increasing over the years. However, no published prospective studies exist with follow-up periods exceeding 1 month to investigate the cardiac change. This prospective study aimed to investigate the changes in cardiac structure and function in healthy young male lowlanders following long-term migration to HA.MethodsA total of 122 Chinese healthy young males were divided into 2 groups: those migrating to altitudes between 3600 m and 4000 m (low HA group, n = 65) and those migrating to altitudes between 4000 m and 4700 m (high HA group, n = 57). Traditional echocardiographic parameters were measured at sea level, 1 month and 1 year after migration to HA.ResultsAll 4 cardiac chamber dimensions, areas, and volumes decreased after both 1 month and 1 year of HA exposure. This reduction was more pronounced in the high HA group than in the low HA group. Bi-ventricular diastolic function decreased after 1 month of HA exposure, while systolic function decreased after 1 year. Notably, these functional changes were not significantly influenced by altitude differences. Dilation of the pulmonary artery and a progressive increase in pulmonary artery systolic pressure were observed with both increasing exposure time and altitude. Additionally, a decreased diameter of the inferior vena cava and reduced bicuspid and tricuspid blood flow velocity indicated reduced blood flow following migration to the HA.Discussion1 year of migration to HA is associated with decreased blood volume and enhanced hypoxic pulmonary vasoconstriction. These factors contribute to reduced cardiac chamber size and slight declines in bi-ventricular function.

IntroductionCitrus fruit is rich in important functional constituents such as flavonoids, phenolic acids terpenes and other functional substances that play an important role for treating clinical diseases or controlling major agricultural diseases and pests. Plant secondary metabolites have become one of the most important resources of novel lead compounds, especially young citrus fruits contain multiple functional substances. ‘Orah’, a type of citrus reticulata, is known for its fine appearance, productivity, delicious sweetness, late-maturing characteristics, and is widely cultivated in China. Fruit thinning and rootstock selection are commonly used agronomic measures in its production to ensure its quality and tree vigor. However, few studies have demonstrated the effects of these agronomic measures on the functional substances of ‘Orah’.MethodsIn this study, we used HPLC coupled with UV to detect the dynamic changes of fruit quality, 13 main flavonoids, 7 phenolic acids, 2 terpenes, synephrine and antioxidant capacity in both peel and pulp of citrus fruits grafted on four rootstocks (Red orange Citrus reticulata Blanco cv. red tangerine, Ziyang xiangcheng Citrus junos Sieb. ex Tanaka, Trifoliate orange Poncirus trifoliata L. Raf, and Carrizo citrange Citrus sinensis Osb.×P.trifoliate Raf) at six different developmental stages (from 90 DAF to 240 DAF).ResultsThe results indicated that rootstock can significantly affect the contents of functional constituents and antioxidant capacity in ‘Orah’. Additionally, it was found that pruning at either 90 DAF (days after flowering) or 150 DAF produced the most favorable outcomes for extracting functional substances. We also identified rootstock ‘Trifoliate orange’ has the highest total soluble solids (TSS) and ‘Ziyang xiangcheng’ to be the optimal in terms of comprehensive sensory of fruit quality, while ‘Red orange’ and ‘Ziyang xiangcheng’ are optimal in terms of functional substance quality, and ‘Red orange’ excels in antioxidant capacity.DiscussionOverall, the findings demonstrate the important role of rootstocks and developmental stage in shaping fruit sensory quality and functional substance synthesis, providing valuable insights for guiding rootstock selection, determining thinning time, and utilizing pruned fruits in a more informed manner.

Remdesivir (RDV) is the first drug approved by the FDA for clinical treatment of hospitalized patients infected with COVID-19 because it has been shown to have good antiviral activity against a variety of viruses, including Arenaviridae and Coronaviridae viral families. However, it has been reported that its clinical treatment leads to the symptoms of sick sinus syndrome such as sinus bradycardia, conduction block, and sinus arrest, but the electrophysiological mechanism of its specific cardiac adverse events is still unclear. We report complementary, experimental, studies of its electrophysiological effects. In wireless cardiac telemetry experiments in vivo and electrocardiographic studies in ex vivo cardiac preparations, RDV significantly caused sinus bradycardia, sinus atrial block, and prolongation of the QT interval in guinea pigs. Dose-dependent effects of RDV on the electrical activities of sinoatrial node (SA node) preparations of guinea pigs were characterised by multielectrode, optical RH237 voltage mapping. These revealed reversibly reduced sinoatrial conduction time (SACT), increased AP durations (APDs), and decreased the pacemaking rate of the SA node. Patch-clamp experiments showed that RDV significantly inhibited the If current of HCN4 channels, resulting in a significant decrease in the spontaneous firing rate of SA node cells, which may underlie the development of sick sinus node syndrome. In addition, RDV significantly inhibits IKr currents in hERG channels, leading to prolongation of the QT interval and playing a role in bradycardia. Therefore, these findings provide insights into the understanding the bradycardia effect of RDV, which may be used as basic theoretical guidance for the intervention of its adverse events, and prompt safety investigations of RDV’s cardiac safety in the future.

Acute intermittent porphyria (AIP) is caused by mutations in the gene encoding hydroxymethylbilane synthase (HMBS), a key enzyme in the heme biosynthesis pathway. AIP is an autosomal dominant disorder characterized by low penetrance and a highly heterogenous clinical presentation. The estimated prevalence of AIP is 5–10 cases per 100,000 persons, with acute attacks manifesting in less than 1% of the at-risk population. This low frequency of attacks suggests significant roles for oligogenic inheritance and environmental factors in the pathogenesis of the disease. In recent years, identification of several modifier genes has advanced our understanding of the factors influencing AIP penetrance and disease severity. This review summarizes these factors including the impact of specific HMBS mutations, oligogenic inheritance, mitochondrial DNA copy number, age, sex, the influence of sex hormones, and the role of environmental factors. Further studies into the etiology of AIP disease penetrance should inform pathogenesis, potentially allowing for the development of more precise diagnostic and therapeutic approaches.

In recent years, protein homeostasis imbalance caused by endoplasmic reticulum stress has become a major hallmark of cancer. Studies have shown that endoplasmic reticulum stress is closely related to the occurrence, development, and drug resistance of non-small cell lung cancer, however, the role of various endoplasmic reticulum stress-related genes in non-small cell lung cancer is still unclear. In this study, we established an endoplasmic reticulum stress scores based on the Cancer Genome Atlas for non-small cell lung cancer to reflect patient features and predict prognosis. Survival analysis showed significant differences in overall survival among non-small cell lung cancer patients with different endoplasmic reticulum stress scores. In addition, endoplasmic reticulum stress scores was significantly correlated with the clinical features of non-small cell lung cancer patients, and can be served as an independent prognostic indicator. A nomogram based on endoplasmic reticulum stress scores indicated a certain clinical net benefit, while ssGSEA analysis demonstrated that there was a certain immunosuppressive microenvironment in high endoplasmic reticulum stress scores. Gene Set Enrichment Analysis showed that scores was associated with cancer pathways and metabolism. Finally, weighted gene co-expression network analysis displayed that CAV1 was closely related to the occurrence of non-small cell lung cancer. Therefore, in order to further analyze the role of this gene, Chinese non-smoking females were selected as the research subjects to investigate the relationship between CAV1 rs3779514 and susceptibility and prognosis of non-small cell lung cancer. The results showed that the mutation of rs3779514 significantly reduced the risk of non-small cell lung cancer in Chinese non-smoking females, but no prognostic effect was found. In summary, we proposed an endoplasmic reticulum stress scores, which was an independent prognostic factor and indicated immune characteristics in the microenvironment of non-small cell lung cancer. We also validated the relationship between single nucleotide polymorphism locus of core genes and susceptibility to non-small cell lung cancer.

As a chronic autoimmune disease with complex aetiology, rheumatoid arthritis (RA) has been demonstrated to be associated with mitochondrial dysfunction since mitochondrial dysfunction can affect the survival, activation, and differentiation of immune and non-immune cells involved in the pathogenesis of RA. Nevertheless, the mechanism behind mitochondrial dysfunction in RA remains uncertain. Accordingly, this review addresses the possible role and mechanisms of mitochondrial dysfunction in RA and discusses the potential and challenges of mitochondria as a potential therapeutic strategy for RA, thereby providing a breakthrough point in the prevention and treatment of RA.

This study proposes an ultra-wideband radar cross section (RCS) reduction technique based on reflection phase interference cancellation and tunable absorption. The operational frequency band of the combined structure is enhanced by uniting two overlapped frequency ranges effectively. As proof of concept, a demonstration structure is designed with a stacked chessboard and an active frequency selective surface (AFSS) absorber. The upper chessboard constructed of a square loop and circular patch unit cells can realize destructive phase interference performance at higher frequencies, while the bottom AFSS absorber achieves tunable absorption at a lower frequency range. Three-dimensional scattering patterns at low and high frequencies are analyzed to verify these two different RCS reduction mechanisms. The combined fabrication structure can obtain an ultra-wideband RCS reduction of more than 10 dB from 4.4 to 36.5 GHz, compared to a metallic plate of the same size, indicating good agreement between full-wave simulation and measurements.

The carbon nitride (C3N4) materials and hybrids have been acknowledged as promising photocatalysts for decades. The precise design and modulation of C3N4-based photocatalyst in defects and energy bands for further promotion is of importance but less investigated. In this work, a type of defective V2O5/C3N4 heterojunction with dual oxygen and carbon vacancy on interface is designed through simple annealing and plasma etching. The incorporation of V2O5 enables to promote the separation efficiency for photo-induced carriers and enhance built-in electric field (BIEF) at junction boundary to accelerate charge transport. The designed double defects in V2O5/C3N4 further results in a type-II heterojunction and switch of redox reaction sites, preventing photocatalytic corrosion of unstable V2O5. As a result, owing to the integrated advantages of such composite photocatalyst, the defective V2O5/C3N4 heterojunction exhibits a comparable hydrogen evolution rate of 0.90 mmol·g−1·h−1 to V2O5/C3N4, and dramatically improved regeneration with a continuous hydrogen evolution rate of 0.83 mmol·g−1·h−1 for 5 cycles. Our study is envisaged to provide a toolbox for rationally designing compositive nanomaterials toward high-efficiency photocatalytic systems.

Introduction: To enhance the beef cattle industry, Heilongjiang Province has developed a new Crossbred beef cattle variety through crossbreeding with exotic commercial breeds. This new variety exhibits relatively excellent meat quality, and efficient reproductive performance, catering to market demands.Method: This study employed whole genome resequencing technology to analyze the genetic pedigree and diversity of 19 Heilongjiang Crossbred beef cattle, alongside 59 published genomes from East Asian, Eurasian, and European taurine cattle as controls. In addition, genes related to production traits were also searched by identifying Runs of Homozygosity (ROH) islands and important fragments from ancestors.Results: A total of 14,427,729 biallelic SNPs were discovered, with the majority located in intergenic and intron regions and a small percentage in exon regions, impacting protein function. Population genetic analyses including Principal Component Analysis (PCA), Neighbor-Joining (NJ) tree, and ADMIXTURE identified Angus, Holstein, and Mishima as the main ancestors of Crossbred beef cattle. In genetic diversity analysis, nucleotide diversity, linkage disequilibrium, and inbreeding coefficient analysis reveal that the genetic diversity of Crossbred beef cattle is at a moderate level, and a higher inbreeding coefficient indicates the need for careful breeding management. In addition, some genes related to economic traits are identified through the identification of Runs of Homozygosity (ROH) islands and important fragments from ancestors.Conclusion: This comprehensive genomic characterization supports the targeted improvement of economically important traits in Crossbred beef cattle, facilitating advanced breeding strategies.

ObjectiveSelecting between programmed cell death ligand 1 (PD-L1) inhibitor or programmed cell death 1 (PD-1) inhibitor plus chemotherapy as first-line treatment for extensive-stage small cell lung cancer (ES-SCLC) patients urgently needs to be answered.MethodsEligible phase 3 randomized clinical trials evaluating regimens based on PD-1/PD-L1 inhibitors as first-line treatment in ES-SCLC patients were systematically searched on the PubMed and Cochrane Library databases and major international conferences from 01/01/2018 to 18/09/2023. The individual patient data (IPD) were recuperated from the Kaplan–Meier curves of the overall survival (OS) and progression-free survival (PFS) of the included studies using the IPDfromKM method. The reconstructed data were pooled into unified arms, including the PD-L1 inhibitor plus chemotherapy group (PD-L1 group), PD-1 inhibitor plus chemotherapy group (PD-1 group), and PD-1 (L1) inhibitor and chemotherapy plus other (anlotinib group, tiragolumab group, and tremelimumab group). Subsequently, the PD-L1 group was indirectly compared with the other groups. A standard statistical analysis was conducted using the “survival” package for the time-to-event endpoint. The primary outcomes were the OS and PFS of the PD-L1 group and the PD-1 inhibitor group. The secondary outcomes included safety and the 12- and 24-month restricted mean survival time (RMST) of the PD-L1 group and PD-1 group.ResultsA total of 9 studies including 11 immunotherapy cohorts were included. No significant difference in PFS (hazard ratio [HR]: 0.96, 95% confidence interval [CI]: 0.86–1.06), OS (HR: 0.94, 95% CI: 0.84–1.05), and 12-month and 24-month RMST for OS (P = 0.198 and P = 0.216, respectively) was observed between the PD-L1 group and the PD-1 group. In contrast, the anlotinib group showed significantly better OS (HR: 0.70, 95% CI: 0.55–0.89), PFS (HR: 0.69, 95% CI: 0.58–0.83), and RMST for OS compared to the PD-L1 group. The tiragolumab group showed similar efficacy to the PD-L1 group. However, the tremelimumab group exhibited inferior efficacy than the PD-L1 group. The incidence of ≥grade 3 treatment-emergent adverse events (TEAEs) was significantly higher in the PD-1 group compared to the PD-L1 group (85.4% vs. 69.6%, P

Abstract Pleckstrin homology domain-containing family M member 2 (PLEKHM2) is an essential adaptor for lysosomal trafficking and its homozygous truncation have been reported to cause early onset dilated cardiomyopathy (DCM). However, the molecular mechanism of PLEKHM2 deficiency in DCM pathogenesis and progression is poorly understood. Here, we generated an in vitro model of PLEKHM2 knockout (KO) induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to elucidate the potential pathogenic mechanism of PLEKHM2-deficient cardiomyopathy. PLEKHM2-KO hiPSC-CMs developed disease phenotypes with reduced contractility and impaired calcium handling. Subsequent RNA sequencing (RNA-seq) analysis revealed altered expression of genes involved in mitochondrial function, autophagy and apoptosis in PLEKHM2-KO hiPSC-CMs. Further molecular experiments confirmed PLEKHM2 deficiency impaired autophagy and resulted in accumulation of damaged mitochondria, which triggered increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential (Δψm). Importantly, the elevated ROS levels caused oxidative stress-induced damage to nearby healthy mitochondria, resulting in extensive Δψm destabilization, and ultimately leading to impaired mitochondrial function and myocardial contractility. Moreover, ROS inhibition attenuated oxidative stress-induced mitochondrial damage, thereby partially rescued PLEKHM2 deficiency-induced disease phenotypes. Remarkably, PLEKHM2-WT overexpression restored autophagic flux and rescued mitochondrial function and myocardial contractility in PLEKHM2-KO hiPSC-CMs. Taken together, these results suggested that impaired mitochondrial clearance and increased ROS levels play important roles in PLEKHM2-deficient cardiomyopathy, and PLEKHM2-WT overexpression can improve mitochondrial function and rescue PLEKHM2-deficient cardiomyopathy.

Abstract In recent years, human umbilical cord mesenchymal stem cell (hUC-MSC) extracellular vesicles (EVs) have been used as a cell replacement therapy and have been shown to effectively overcome some of the disadvantages of cell therapy. However, the specific mechanism of action of EVs is still unclear, and there is no appropriate system for characterizing the differences in the molecular active substances of EVs produced by cells in different physiological states. We used a data-independent acquisition (DIA) quantitative proteomics method to identify and quantify the protein composition of two generations EVs from three different donors and analysed the function and possible mechanism of action of the proteins in EVs of hUC-MSCs via bioinformatics. By comparative proteomic analysis, we characterized the different passages EVs. Furthermore, we found that adaptor-related protein complex 2 subunit alpha 1 (AP2A1) and adaptor-related protein complex 2 subunit beta 1 (AP2B1) in hUC-MSC-derived EVs may play a significant role in the treatment of Alzheimer's disease (AD) by regulating the synaptic vesicle cycle signalling pathway. Our work provides a direction for batch-to-batch quality control of hUC-MSC-derived EVs and their application in AD treatment.

Abstract Background Spermatogonial stem cells (SSCs) are the foundation cells for continual spermatogenesis and germline regeneration in mammals. SSC activities reside in the undifferentiated spermatogonial population, and currently, the molecular identities of SSCs and their committed progenitors remain unclear. Results We performed single-cell transcriptome analysis on isolated undifferentiated spermatogonia from mice to decipher the molecular signatures of SSC fate transitions. Through comprehensive analysis, we delineated the developmental trajectory and identified candidate transcription factors (TFs) involved in the fate transitions of SSCs and their progenitors in distinct states. Specifically, we characterized the Asingle spermatogonial subtype marked by the expression of Eomes. Eomes+ cells contained enriched transplantable SSCs, and more than 90% of the cells remained in the quiescent state. Conditional deletion of Eomes in the germline did not impact steady-state spermatogenesis but enhanced SSC regeneration. Forced expression of Eomes in spermatogenic cells disrupted spermatogenesis mainly by affecting the cell cycle progression of undifferentiated spermatogonia. After injury, Eomes+ cells re-enter the cell cycle and divide to expand the SSC pool. Eomes+ cells consisted of 7 different subsets of cells at single-cell resolution, and genes enriched in glycolysis/gluconeogenesis and the PI3/Akt signaling pathway participated in the SSC regeneration process. Conclusions In this study, we explored the molecular characteristics and critical regulators of subpopulations of undifferentiated spermatogonia. The findings of the present study described a quiescent SSC subpopulation, Eomes+ spermatogonia, and provided a dynamic transcriptional map of SSC fate determination.

Abstract N6-methyladenosine (m6A) modification, as a common epigenetic modification, has been widely studied in autoimmune diseases. However, the role of m6A in the regulation of the immune microenvironment of ankylosing spondylitis (AS) remains unclear. Therefore, we aimed to investigate the effect of m6A modification on the immune microenvironment of AS. We first evaluated RNA modification patterns mediated by 26 m6A regulators in 52 AS samples and 20 healthy samples. Thereafter, an m6A related classifier composed of seven genes was constructed and could effectively distinguish healthy and AS samples. Then, the correlation between m6A regulators and immune characteristics were investigated, including infiltrating immunocytes, immune reactions activity, and human leukocyte antigen (HLA) genes expression. The results indicated that m6A regulators was closely correlated with immune characteristics. For example, EIF3A was significantly related to infiltrating immunocytes; IGF2BP2 and EIF3A were significant regulators in immune reaction of TGF-β family member, and the expression of HLA-DPA1 and HLA-E were affected by EIF3A and ALKBH5. Next, two distinct m6A expression patterns were identified through unsupervised clustering analysis, and diverse immune characteristics were found between them. A total of 5889 m6A phenotype-related genes were obtained between the two expression patterns, and their biological functions were revealed. Finally, we validated the expression status of m6A modification regulators using two additional datasets. Our findings illustrate that m6A modifications play a critical role in the diversity and complexity of the AS immune microenvironment.

Abstract Ruthenium (Ru) has been recognized as a prospective candidate to substitute platinum catalysts in water‐splitting‐based hydrogen production. However, minimizing the Ru contents, optimizing the water dissociation energy of Ru sites, and enhancing the long‐term stability are extremely required, but still face a great challenge. Here, we report on creating tungsten oxide‐anchored Ru clusters (Ru–WOx) with electron‐rich and anti‐corrosive microenvironments for efficient and robust seawater splitting. Benefiting from the abundant oxygen vacancy structure in tungsten oxide support, the Ru–WOx exhibits strong Ru–O and Ru–W bonds at the interface. Our study elucidates that the strong Ru–O bonds in Ru–WOx may accelerate the water dissociation kinetics, and the Ru–W bonds will lead to the strong metal–support interaction and electrons transfer from W to Ru. The optimal Ru–WOx catalysts exhibit a low overpotential of 29 and 218 mV at the current density of 10 mA cm−2 in alkaline and seawater media, respectively. The outstanding long‐term stability discloses that the Ru–WOx catalysts own efficient corrosion resistance in seawater electrolysis. We believe that this work offers new insights into the essential roles of electron‐rich and anti‐corrosive microenvironments in Ru‐based catalysts and provide a new pathway to design efficient and robust cathodes for seawater splitting.

While consensus on single-incision laparoscopic appendectomy (SILA) for acute appendicitis is lacking, our meta-analysis evaluated the safety and efficacy of SILA compared to conventional three-port laparoscopic appendectomy (CTLA). A computer-based search was conducted in the China National Knowledge Infrastructure (CNKI), VIP, Wanfang, China Biological Medicine (CBM), PubMed, Embase, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing SILA with CTLA groups. Meta-analysis was performed using RevMan 5.3 software. A total of 26 RCTs were included. The meta-analysis results indicated that, compared to the CTLA group, the SILA group had a longer operation time [MD = 7.97, 95 % CI (5.84, 10.10), P

Abstract Objective (1) This study aims to identify distinct serum metabolites in gastric cancer patients compared to healthy individuals, providing valuable insights into postoperative efficacy evaluation and monitoring of gastric cancer recurrence; (2) Methods: Serum samples were collected from 15 healthy individuals, 16 gastric cancer patients before surgery, 3 months after surgery, 6 months after surgery, and 15 gastric cancer recurrence patients. T-test and analysis of variance (ANOVA) were performed to screen 489 differential metabolites between the preoperative group and the healthy control group. Based on the level of the above metabolites in the recurrence, preoperative, three-month postoperative, and six-month postoperative groups, we further selected 18 significant differential metabolites by ANOVA and partial least squares discriminant analysis (PLS-DA). The result of hierarchical clustering analysis about the above metabolites showed that the samples were regrouped into the tumor-bearing group (comprising the original recurrence and preoperative groups) and the tumor-free group (comprising the original three-month postoperative and six-month postoperative groups). Based on the results of PLS-DA, 7 differential metabolites (VIP > 1.0) were further selected to distinguish the tumor-bearing group and the tumor-free group. Finally, the results of hierarchical clustering analysis showed that these 7 metabolites could well identify gastric cancer recurrence; (3) Results: Lysophosphatidic acids, triglycerides, lysine, and sphingosine-1-phosphate were significantly elevated in the three-month postoperative, six-month postoperative, and healthy control groups, compared to the preoperative and recurrence groups. Conversely, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol were significantly reduced in the three-month postoperative, six-month postoperative, and healthy control groups compared to the preoperative and recurrence groups. However, these substances did not show significant differences between the preoperative and recurrence groups, nor between the three-month postoperative, six-month postoperative, and healthy control groups; (4) Conclusions: Our findings demonstrate the presence of distinct metabolites in the serum of gastric cancer patients compared to healthy individuals. Lysophosphatidic acid, triglycerides, lysine, sphingosine-1-phosphate, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol hold potential as biomarkers for evaluating postoperative efficacy and monitoring recurrence in gastric cancer patients. These metabolites exhibit varying concentrations across different sample categories.

Modern unmanned aerial vehicle (UAV) reconnaissance is widely used. UAV equipped with FPV camera can realize the reconnaissance of dense small objects with the help of object detection technology. However, it is difficult to detect people or vehicle objects in UAV overhead images because the pixels are small and densely distributed. In this paper, we propose an improved YOLOv7 UAV dense small object detection algorithm (DS-YOLOv7) to improve the UAV detection performance of dense small objects. SFN technology optimizes the fusion network to further improve the semantic information and location information of dense small objects. LDSPP is an optimized module for feature extraction of small objects. It pays more attention to edge information of small objects and reduces the rate of missing detection. Dimensionality reduction techniques focus on reducing model parameters to facilitate the deployment of algorithms on lightweight devices. The experimental verification on the public data set VisDrone2019 shows that mAP50 and mAP50-95 have increased by 4.3% and 3.3% respectively, F1 scores have increased by 3.81%, model volume has decreased by 23.3MB, parameters have decreased by 13 million, and the improved algorithm is more conducive to UAV deployment and dense small object detection.

In this paper, a fully tunable bandpass filter (BPF) with three states of filtering (single passband state, dual passband state and all-off state) is proposed, the proposed fully tunable BPF is cascaded by a tunable low pass filter section (LP) and a tunable high pass filter section(HP). By introducing a switchable dual-mode notch in the passband, the proposed BPF is capable of operating in single, dual passband and all-off state, demonstrating high flexibility in working mode. Tunable LP and HP filters with 7-order generalized Chebyshev response are designed to improve the roll-off rate and out-of-band rejection level of the BPF. The measured results show that the bandwidth of the BPF can be tuned from 0.25GHz to 2.69GHz (10.8:1), and the center frequency can be tuned from 2.9GHz to 4.6GHz with constant absolute bandwidth of 1GHz. Besides, high rejection level of out-of-band is realized in all working mode. The high flexibility in working mode makes the proposed fully tunable BPF very attractive in carrier aggregation scenarios.

Abstract Background The selection of diverting ileostomy (DI) is controversial. This study aimed to explore the factors affecting the selection of diverting ileostomy (DI) following laparoscopic low anterior resection for rectal cancer. Methods This retrospective, case-control study included patients who underwent laparoscopic-assisted sphincter-saving surgery for mid-low rectal cancer from January 2019 to June 2021. Univariate and multivariate analyses were performed on the patient’s clinicopathological characteristics and pelvic dimensions measured by abdominopelvic electron beam computed tomography. Results A total of 382 patients were included in the analysis, of which 182 patients (47.6%) did not undergo DI, and 200 patients (52.4%) underwent DI. The univariate analysis suggested that male sex (p = 0.003), preoperative radiotherapy (p