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Abstract Background Neuroinflammation is a vital pathogenic mechanism for neurodegenerative diseases such as Alzheimer’s, schizophrenia, and age-related cognitive decline. Regulatory T cells (Tregs) exhibit potent anti-inflammatory properties and can modulate neurodegenerative diseases arising from central nervous system inflammatory responses. However, the role of Tregs in neuroinflammation-related cognitive dysfunction remains unclear. It is highly plausible that Htr7+ Tregs expressing unique genes associated with the nervous system, including the Htr7 gene encoding the serotonin receptor 5-HT7, play a pivotal role. Methods Mice were given a tryptophan-rich diet (with a tryptophan content of 0.6%) or a normal diet (with a tryptophan content of 0.16%). The neuroinflammation-mediated cognitive dysfunction model was established by intracerebroventricular injection of lipopolysaccharide (LPS) in 8-week-old C57BL/6J mice. The activation and infiltration of Tregs were measured using flow cytometry. Primary Tregs were cocultured separately with primary CD8+ T cells and primary microglia for in vitro validation of the impact of 5-HT and 5-HT7 receptor on Tregs. Prior to their transfer into recombination activating gene 1 (Rag1−/−) mice, Tregs were ex vivo transfected with lentivirus to knock down the expression of Htr7. Results In this study, the tryptophan-rich diet was found to reverse LPS-induced cognitive impairment and reduce the levels of 5-HT in peripheral blood. The tryptophan-rich diet led to increased levels of 5-HT in peripheral blood, which in turn promoted the proliferation and activation of Htr7+ Tregs. Additionally, the tryptophan-rich diet was also shown to attenuate LPS-mediated neuroinflammation by activating Htr7+ Tregs. Furthermore, 5-HT and 5-HT7 receptor were found to enhance the immunosuppressive effect of Tregs on CD8+ T cells and microglia. In Rag1−/− mice, Htr7+ Tregs were shown to alleviate LPS-induced neuroinflammation and cognitive impairment. Conclusions Our research revealed the ability of Htr7+ Tregs to mitigate neuroinflammation and prevent neuronal damage by suppressing the infiltration of CD8+ T cells into the brain and excessive activation of microglia, thereby ameliorating LPS-induced cognitive impairment. These insights may offer novel therapeutic targets involving Tregs for neuroinflammation and cognitive impairment.

The mechanical properties, texture transformation, and mechanism of Al–Cu–Mn alloy during annealing were studied using three-dimensional orientation distribution function (ODF), electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM). The results showed that the increase in yield strength after annealing at 200 °C is due to the decrease in the proportion of P and M textures and the increase in the proportion of Goss texture. The increase in the change rate of mechanical properties observed during annealing at 250 and 350 °C can be attributed to the higher proportion of M and P textures and the reduced proportion of Goss textures. Among them, the proportion of M texture increased significantly, and the Goss texture decreased significantly after annealing at 350 °C. This is because the structural energy density (Ev) value of the Goss texture is higher than that of the M texture at 250 °C and 350 °C. The Goss texture is in an unstable state of high energy order. The deformed Goss texture is unstable at high temperatures, leading to conversion into M and other textures. The EBSD and TEM analysis revealed that the hardness is mainly related to the change in dislocation density. When the annealing temperature is increased from 250 to 350 °C, the hardness is significantly reduced from 62 HV to 52 HV, and the dislocation density is reduced from 4.0 × 1014 ρ/m−2 to 2.4 × 1014 ρ/m−2.

Abstract During the progression of proliferative vitreoretinopathy (PVR) following ocular trauma, previously quiescent retinal pigment epithelial (RPE) cells transition into a state of rapid proliferation, migration, and secretion. The elusive molecular mechanisms behind these changes have hindered the development of effective pharmacological treatments, presenting a pressing clinical challenge. In this study, by monitoring the dynamic changes in chromatin accessibility and various histone modifications, we chart the comprehensive epigenetic landscape of RPE cells in male mice subjected to traumatic PVR. Coupled with transcriptomic analysis, we reveal a robust correlation between enhancer activation and the upregulation of the PVR-associated gene programs. Furthermore, by constructing transcription factor regulatory networks, we identify the aberrant activation of enhancer-driven RANK-NFATc1 pathway as PVR advanced. Importantly, we demonstrate that intraocular interventions, including nanomedicines inhibiting enhancer activity, gene therapies targeting NFATc1 and antibody therapeutics against RANK pathway, effectively mitigate PVR progression. Together, our findings elucidate the epigenetic basis underlying the activation of PVR-associated genes during RPE cell fate transitions and offer promising therapeutic avenues targeting epigenetic modulation and the RANK-NFATc1 axis for PVR management.

Abstract Ring cavities are quickly emerging as preferential platforms to investigate spontaneous symmetry breaking. However, research on handedness polarisation splitting within Kerr-coupled cavities is yet at a preliminary stage. Here, we observe experimentally spontaneous symmetry breaking in a non-Hermitian coupled Fabry‒Pérot nanocavity. In the experiment, horizontally polarised light is incident on the nanocavities, and symmetry breaking occurs when the power exceeds the symmetry breaking threshold of $$8\,{{\mbox{mW}}}$$ 8 mW . We interpret such observation via nonlinear coupled mode theory, finding that an excitation power-dependent random splitting of right- or left-handed circular polarisations (RCP and LCP, respectively) emerges at the resonance peak. Further numerical simulations show that when the incident power is above the symmetry breaking threshold, the device exhibits spontaneous symmetry breaking characteristics: an additional polarisation component appears in the output field when the input field is monopolarised, and this is attributed to the imbalance of RCP and LCP. Our findings provide further understanding of spontaneous symmetry breaking in non-Hermitian systems and demonstrate the potential applications of the proposed device in optical signal processing.

Abstract Hyperuricemia (HUA) is a common metabolic disease and kidney injury is one of its main complications. As a typical natural flavonoid, puerarin (PEA) has a range of pharmacological activity but the antihyperuricemic mechanism of PEA has not been reported. Herein, the inhibitory activity of PEA against xanthine oxidase (XOD) was evaluated by in vitro enzymatic reaction, and kinetic analysis, the antihyperuricemic activity, and nephroprotective effect of PEA were studied in HUA mice. The enzymatic reaction showed that the inhibitory effect of PEA (half maximal inhibitory concentration [IC50] = 4.39 µmol/L) on XOD was at the same level as allopurinol (IC50 = 4.05 µmol/L), and kinetic analysis indicated that PEA was a mixed competitive inhibitor. In vivo studies demonstrated that PEA exhibited excellent antihyperuricemic activity by inhibiting XOD and urate transporter 1 (URAT1), to reduce uric acid level. At the same time, PEA reduced the level of inflammatory cytokines and exerted significant nephroprotective effect through anti‐inflammatory activity. Molecular docking indicated that PEA closely bind to both XOD and URAT1, which had the potential to become an inhibitor of XOD and URAT1. In summary, PEA has important application value in developing novel functional food and medicine for the treatment of HUA and its complications.

To ameliorate the diminished antimicrobial efficiency and physiological stability associated with monomeric antimicrobial peptides (AMPs) molecules, future research will focus on the artificial design of self-assembling peptides to replace monomeric entities, aiming to combat the antibiotic resistance crisis caused by microbial infections. In this study, the “bola” structure was used as the foundational architecture driving molecular self-assembly, with hydrophobic amino acids at the termini to anchor and finely adjust the sequence, thereby organizing a range of novel multidomain peptides (MDPs) templates into an ABA block motif. The results indicate that FW2 (GMSI = 53.94) exhibits the highest selectivity index among all MDPs and can form spherical micelles in an aqueous medium without the addition of any exogenous additives. FW2 exhibited high stability in vitro in the presence of physiological salt ions, serum, and various pH conditions. It exhibited excellent biocompatibility and efficacy both in vivo and in vitro. Furthermore, FW2 strongly interacts with the lipid membrane and employs various synergistic mechanisms, such as reactive oxygen species (ROS) accumulation, collectively driving cellular apoptosis. This study demonstrates a straightforward strategy for designing self-assembling peptides and promotes the advancement of peptide-based biomaterials integration progress with nanotechnology.

BackgroundThe human epidermal growth factor receptor 2 gene (HER2) has been identified as a potential therapeutic target in lung adenocarcinoma (LUAD). Non-invasive positron emission tomography (PET) imaging provides a reliable strategy for in vivo determination of HER2 expression through whole-body detection of abnormalities. The PET tracer 68Ga-NOTA-MAL-Cys-MZHER2:342 has shown promising results for HER2-positive breast and gastric cancers. This study aims to evaluate the performance of 68Ga-NOTA-MAL-Cys-MZHER2:342in vitro and in vivo models and in clinical patients with HER2-positive LUAD.MethodsNOTA-MAL-Cys-MZHER2:342 was synthesized and labeled with 68Ga. Cell uptake, cell binding ability, and stability studies of 68Ga-NOTA-MAL-Cys-MZHER2:342 were assessed both in the Calu-3 lung cancer (LC) cell line and normal mice. In vivo assessment in tumor-bearing mice was conducted using microPET imaging and biodistribution experiments. Additionally, preliminary PET/CT imaging analysis was performed on HER2-positive LC patients.Results68Ga-NOTA-MAL-Cys-MZHER2:342 was prepared with a radiochemical purity (RCP) exceeding 95%. The tracer demonstrated high cell uptake in HER2-overexpressing Calu-3 cells, with an IC50 of 158.9, an adequate 1.73 nM. Good stability was exhibited both in vitro and in vivo. MicroPET imaging of Calu-3-bearing mice revealed high tumor uptake and notable tumor-to-background ratios. Positive outcomes were also observed in two HER2-positive LUAD patients.Conclusion68Ga-NOTA-MAL-Cys-MZHER2:342 demonstrated satisfactory stability, sensitivity, and specificity. These findings suggest that 68Ga-NOTA-MAL-Cys-MZHER2:342 PET/CT imaging provides a novel tool for non-invasive visual assessment of HER2 expression in LUAD patients.

Scrophularia ningpoensis Hemsl. (SN) is an herbal medicine used as a functional food in China. SN has traditionally been used to treat diabetes mellitus (DM), but its mechanism of action is not well understood. Our previous study indicated that the aqueous extract of SN can reduce hepatic insulin resistance and correct the irregular shape of pancreatic islets in diabetic mice. This study aims to investigate whether the aqueous extract of SN can regulate pyroptosis in pancreatic β-cells and explore its underlying mechanisms. Db/db mice were orally given an aqueous extract of SN for eight weeks. Subsequently, their pancreatic tissues were collected for histopathological analysis and immunoblotting. Rat insulinoma (INS-1) cells were cultured either alone or with the aqueous extract of SN and evaluated for cell viability, pyroptotic body formation, AMP-activated protein kinase (AMPK) activity, the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome and gasdermin D (GSDMD) activation, and reactive oxygen species (ROS) production under high glucose (HG) exposure conditions. The aqueous extract of SN reduced insulitis and pancreatic β-cell death in db/db mice. Increased AMPK phosphorylation and decreased NLRP3 inflammasome and GSDMD activation were observed in pancreatic tissues after administration of the aqueous extract of SN. In vitro, the aqueous extract of SN increased cell viability and AMPK phosphorylation in a concentration-dependent manner. Additionally, the aqueous extract of SN corrected excessive ROS generation, NLRP3 inflammasome and GSDMD activation, and pyroptotic body formation. Inhibition of AMPK negated these beneficial effects of the aqueous extract of SN on INS-1 cells. The study concluded that the aqueous extract of SN alleviates β-cell pyroptosis by inhibiting NLRP3/GSDMD activation in an AMPK-dependent manner.

Abstract Background Mitochondrial genome abnormalities can lead to mitochondrial dysfunction, which in turn affects cellular biology and is closely associated with the development of various diseases. The demand for mitochondrial DNA (mtDNA) sequencing has been increasing, and Illumina and MGI are two commonly used sequencing platforms for capture-based mtDNA sequencing. However, there is currently no systematic comparison of mtDNA sequencing performance between these two platforms. To address this gap, we compared the performance of capture-based mtDNA sequencing between Illumina's NovaSeq 6000 and MGI's DNBSEQ-T7 using tissue, peripheral blood mononuclear cell (PBMC), formalin-fixed paraffin-embedded (FFPE) tissue, plasma, and urine samples. Results Our analysis indicated a high degree of consistency between the two platforms in terms of sequencing quality, GC content, and coverage. In terms of data output, DNBSEQ-T7 showed higher rates of clean data and duplication compared to NovaSeq 6000. Conversely, the amount of mtDNA data obtained by per gigabyte sequencing data was significantly lower in DNBSEQ-T7 compared to NovaSeq 6000. In terms of detection mtDNA copy number, both platforms exhibited good consistency in all sample types. When it comes to detection of mtDNA mutations in tissue, FFPE, and PBMC samples, the two platforms also showed good consistency. However, when detecting mtDNA mutations in plasma and urine samples, significant differenceof themutation number detected was observed between the two platforms. For mtDNA sequencing of plasma and urine samples, a wider range of DNA fragment size distribution was found in NovaSeq 6000 when compared to DNBSEQ-T7. Additionally, two platforms exhibited different characteristics of mtDNA fragment end preference. Conclusions In summary, the two platforms generally showed good consistency in capture-based mtDNA sequencing. However, it is necessary to consider the data preferences generated by two sequencing platforms when plasma and urine samples were analyzed.

Abstract Background In the past quite a long time, intraoperative cholangiography(IOC)was necessary during laparoscopic cholecystectomy (LC). Now magnetic resonance cholangiopancreatography (MRCP) is the main method for diagnosing common bile duct stones (CBDS). Whether MRCP can replace IOC as routine examination before LC is still inconclusive. The aim of this study was to analyze the clinical data of patients undergoing LC for cholecystolithiasis, and to explore the necessity and feasibility of preoperative routine MRCP in patients with cholecystolithiasis. Methods According to whether MRCP was performed before operation, 184 patients undergoing LC for cholecystolithiasis in the Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University from January 1, 2017 to December 31, 2018 were divided into non-MRCP group and MRCP group for this retrospective study. The results of preoperative laboratory test, abdominal ultrasound and MRCP, biliary related comorbidities, surgical complications, hospital stay and hospitalization expenses were compared between the two groups. Results Among the 184 patients, there were 83 patients in non-MRCP group and 101 patients in MRCP group. In MRCP group, the detection rates of cholecystolithiasis combined with CBDS and common bile duct dilatation by MRCP were higher than those by abdominal ultrasound (P 0.05), but there was significant difference in hospitalization expenses (P 0.05). Conclusions The preoperative MRCP can detect CBDS, cystic duct stones and anatomical variants of biliary tract that cannot be diagnosed by abdominal ultrasound, which is helpful to plan the surgical methods and reduce the surgical complications. From the perspective of health economics, routine MRCP in patients with cholecystolithiasis before LC does not increase hospitalization costs, and is necessary and feasible.

Abstract Objective Clinical approaches to analgesia following total shoulder arthroplasty include liposomal bupivacaine, local infiltration analgesia, single-shot interscalene block, and continuous interscalene block. However, the best method remains contentious. This study conducts a network meta-analysis comparing these four methods, aiming to identify the most effective analgesic approach. Methods Randomized controlled trials on analgesic regimens for total shoulder arthroplasty were identified through searches of PUBMED, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, and Scopus databases, covering their inception through November 2023. Network meta-analysis was performed using STATA 15.1, and the Cochrane Handbook version 5.1.0 risk of bias tool was employed for quality assessment of the literature. Results Twelve randomized controlled trials were included, comprising 1537 patients undergoing total shoulder arthroplasty. The interventions compared were ssISB, cISB, LIA, and LB. Regarding the quality of the literature, four studies were deemed low risk, one high risk, and seven moderate risk. The network meta-analysis revealed that in terms of VAS scores in the PACU, the ssISB group was the most effective, followed by cISB and LB, with LIA being the least effective. This pattern continued in VAS scores on the first and second postoperative days. Regarding morphine consumption, the cISB group showed the most significant reduction in the PACU and on the first postoperative day, while the LIA group performed best in total postoperative morphine consumption. The shortest average hospital stay was noted in the cISB group. Conclusion The ssISB method excels in controlling early postoperative pain, particularly during the PACU stage and early postoperative period. Additionally, the cISB method is notable for reducing postoperative morphine consumption and shortening average hospital stays. While the LIA method ranks first in reducing total morphine consumption, it is weaker in pain control. The LB method is underwhelming across most assessment parameters. These findings underscore the importance of selecting appropriate analgesic strategies for different postoperative recovery phases and provide valuable insights for clinicians to optimize postoperative pain management. Furthermore, they suggest a need for future research to explore the specific application and effectiveness of these methods in varying clinical contexts.

Abstract Pearl oil apricot almonds are rich in proteins, being a valuable raw material for preparing antioxidant peptides. In this study, almond protein hydrolysates (APHs) were obtained by enzymatic hydrolysis and divided into APHs‐1 (10 kDa). APHs‐1‐c, purified from APHs‐1, was proved to show the strongest antioxidant effect through activity tracking experiments. APHs‐1‐c also can protect HepG2 cells against oxidative damage by reducing intracellular reactive oxygen species and MDA levels, elevating glutathione levels as well as increasing superoxide dismutase and catalase activities, and its protective effect is related to the Keap1–Nrf2 signaling pathway. Forty bioactive peptide sequences were identified from APHs‐1‐c, and Thr‐Glu‐Asp‐Asp‐Trp‐Arg‐Trp‐His (TEDDWRWH; P1), Trp‐Tyr‐Asp‐Asn‐Glu‐Trp‐Gly‐Tyr‐Arg (WYDNEWGYR; P2), and Ala‐Glu‐Asp‐His‐Glu‐Trp‐Trp‐Arg (AEDHEWWWR; P3) had the most potential for antioxidant activity by molecular docking studies. P1, P2, and P3 showed desirable 1,1‐diphenyl‐2‐picrylhydrazyl radical scavenging activity (IC50 = 0.634–3.381 mmol/L), 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt radical scavenging activity (IC50 = 0.221–0.309 mmol/L), and ferric‐reducing antioxidant power. These results suggested that almonds protein hydrolysates and its derived antioxidant peptides could serve as potential ingredients applied in functional foods.

Monitoring and controlling the occurrence of hematoma expansion events after a stroke is a primary clinical focus. The introduction of machine learning (ML) techniques offers intelligent decision support for physicians in this domain. However, for doctors without an ML background, the behavior of a hematoma expansion predictor seems opaque, similar to a “black box.” Moreover, the vast and diverse set of features typically present in medical data acts as a double-edged sword: while encapsulating rich information with potential value, it also includes redundant details that offer little to predictive utility. Comprehensive feature selection is crucial, but many current state-of-the-art hematoma expansion prediction studies based on ML often overlook this step. In this paper, we propose a methodology tailored for comprehensive feature selection across diverse and abundant medical data features and rigorously evaluate ML models. Through experiments on a real-world post-stroke hematoma expansion prediction dataset, we demonstrate the efficacy of our approach in enhancing the performance of ML predictors. Visualization of the associated feature selection process and results further bolsters physicians’ understanding of the model’s decision-making basis, thereby strengthening its interpretability.

Abstract The relationship between metallic micronutrients and soil microorganisms, and thereby soil functioning, has been little explored. Here, we investigate the relationship between metallic micronutrients (Fe, Mn, Cu, Zn, Mo and Ni) and the abundance, diversity and function of soil microbiomes. In a survey across 180 sites in China, covering a wide range of soil conditions the structure and function of the soil microbiome are highly correlated with metallic micronutrients, especially Fe, followed by Mn, Cu and Zn. These results are robust to controlling for soil pH, which is often reported as the most important predictor of the soil microbiome. An incubation experiment with Fe and Zn additions for five different soil types also shows that increased micronutrient concentration affects microbial community composition and functional genes. In addition, structural equation models indicate that micronutrients positively contribute to the ecosystem productivity, both directly (micronutrient availability to plants) and, to a lesser extent, indirectly (via affecting the microbiome). Our findings highlight the importance of micronutrients in explaining soil microbiome structure and ecosystem functioning.

Abstract Cashew nut is a globally popular nut not only for its delicious and crunchy flavor but also for bioactive compounds, which present positive benefits to human health. Different parts of cashew have characteristic compounds. The kernel of cashew nut is rich in fatty acids, the testa is rich in polyphenols, cashew apple is rich in polyphenols and carotenoids, and phenols with aliphatic long chain are present in the cashew nutshell liquid. Therefore, the edible part of cashew possesses a wide range of bioactive compounds, with reported biological properties, including anti‐tumor, brain health, cardiovascular and cerebrovascular protection, anti‐diabetic, gastroprotection, pathophysiological disorders protection, and antioxidant. On the other hand, the inedible part of cashew, the cashew nutshell liquid, could play an important role in the industry as surface coatings, insulating formulations and so on. Hence, there are considerable demands to increase the added value of cashew, thereby exploring greater economic value. Thus, this review summarizes nutrients, bioactive compounds, biological functions, and applications of Anacardium occidentale to provide a theoretical basis and inspiration for further in‐depth studies and utilization.

To reduce errors in sub-synchronous oscillation (SSO) modal identification and improve the accuracy and noise resistance of the traditional Prony algorithm, this paper focuses on SSOs caused by the integration of doubly fed induction generators (DFIGs) with series compensation into the grid. A novel SSO modal identification method based on the hippopotamus optimization–variational mode decomposition (HO-VMD) and singular value decomposition–regularized total least squares–Prony (SVD-RTLS-Prony) algorithms is proposed. First, the energy ratio function is used for real-time monitoring of the system to identify oscillation signals. Then, to address the limitations of the VMD algorithm, the HO algorithm’s excellent optimization capabilities were utilized to improve the VMD algorithm, leading to preliminary denoising. Finally, the SVD-RTLS-improved Prony algorithm was employed to further suppress noise interference and extract oscillation characteristics, allowing for the accurate identification of SSO modes. The performance of the proposed method was evaluated using theoretical and practical models on the Matlab and PSCAD simulation platforms. The results indicate that the algorithms effectively perform denoising and accurately identify the characteristics of SSO signals, confirming its effectiveness, accuracy, superiority, and robustness against interference.

Fungal secondary metabolites (SMs) represent an invaluable source of therapeutic drugs. Genomics-based approaches to SM discovery have revealed a vast and largely untapped biosynthetic potential within fungal genomes. Here, we used the publicly available fungal genome sequences from the NCBI public database, as well as tools such as antiSMASH, BIG-SLiCE, etc., to analyze a total of 11,598 fungal genomes, identifying 293,926 biosynthetic gene clusters (BGCs), which were subsequently categorized into 26,825 gene cluster families (GCFs). It was discovered that only a tiny fraction, less than 1%, of these GCFs could be mapped to known natural products (NPs). Some GCFs that only contain a single BGC internally are crucial for the biodiversity of fungal biosynthesis. Evident patterns emerged from our analysis, revealing popular taxa as prominent sources of both actual and potential biosynthetic diversity. Our study also suggests that the genus rank distribution of GCF is generally consistent with NP diversity. It is noteworthy that genera Xylaria, Hypoxylon, Colletotrichum, Diaporthe, Nemania, and Calonectria appear to possess a higher potential for SM synthesis. In addition, 7213 BGCs match possible known compound structures, and homologous gene clusters of well-known drugs can be located in different genera, facilitating the development of derivatives that share structural similarity to these drugs and may potentially possess similar biological activity. Our study demonstrated the various types of fungi with mining potential, assisting researchers in prioritizing their research efforts and avoiding duplicate mining of known resources to further explore fungal NP producers.

Chemoresistance is one of the main reasons for poor prognosis of pancreatic cancer. The effects of mesothelin (MSLN) on chemoresistance in pancreatic cancer are still unclear. We aim to investigate potential roles of MSLN in chemoresistance and its relationship with proliferation, epithelial-mesenchymal transition (EMT) and cancer stemness of pancreatic cancer cells. Human pancreatic cancer cell lines ASPC-1 and Mia PaCa-2 with high and low expression of MSLN, respectively, were selected. The ASPC-1 with MSLN knockout (KO) and Mia PaCa-2 of MSLN overexpression (OE) were generated. The effects of MSLN on cell phenotypes, expression of EMT-related markers, clone formation, tumor sphere formation, and pathologic role of MSLN in tumorigenesis were detected. Sensitivity of tumor cells to gemcitabine was evaluated. The results showed that adhesion, proliferation, migration and invasion were decreased significantly in ASPC-1 with MSLN KO, whereas increased significantly in Mia PaCa-2 with MSLN OE. The size and the number of clones and tumor spheres were decreased in ASPC-1 with MSLN KO, and increased in Mia PaCa-2 with MSLN OE. In xenograft model, tumor volume was decreased (tumor grew slower) in MSLN KO group compared to control group, while increased in MSLN OE group. Mia PaCa-2 with MSLN OE had a higher IC50 of gemcitabine, while ASPC-1 with MSLN KO had a lower IC50. We concluded that MSLN could induce chemoresistance by enhancing migration, invasion, EMT and cancer stem cell traits of pancreatic cancer cells. Targeting MSLN could represent a promising therapeutic strategy for reversing EMT and chemoresistance in pancreatic cancer cells.

BackgroundWe aimed to examine the association between blood levels of Branched-chain amino acids (BCAAs) - specifically isoleucine, leucine, and valine - and the susceptibility to three neurodegenerative disorders: dementia, Alzheimer’s disease (AD), and Parkinson’s disease (PD).MethodsBased on data from the UK Biobank, a Cox proportional hazard regression model and a dose–response relationship were used to analyze the association between BCAAs and the risks of dementia, AD, and PD. We also generated a healthy lifestyle score and a polygenic risk score. Besides, we conducted a sensitivity analysis to ensure the robustness of our findings.ResultsAfter adjusting for multiple covariates, blood concentrations of isoleucine, leucine, and valine were significantly associated with a reduced risk of dementia and AD. This association remained robust even in sensitivity analyses. Similarly, higher levels of isoleucine and leucine in the blood were found to be associated with an increased risk of PD, but this positive correlation could potentially be explained by the presence of covariates. Further analysis using a dose–response approach revealed that a blood leucine concentration of 2.14 mmol/L was associated with the lowest risk of dementia.ConclusionBCAAs have the potential to serve as a biomarker for dementia and AD. However, the specific mechanism through which BCAAs are linked to the development of dementia, AD, and PD remains unclear and necessitates additional investigation.

Abstract Hypertrophic scar formation is influenced by the intricate interplay between fibroblasts and endothelial cells. In this study, we investigated this relationship using in vitro and in vivo models. Clinical observations revealed distinct morphological changes and increased vascularity at pathological scar sites. Further analysis using OCTA, immunohistochemistry, and immunofluorescence confirmed the involvement of angiogenesis in scar formation. Our indirect co‐culture systems demonstrated that endothelial cells enhance the proliferation and migration of fibroblasts through the secretion of cytokines including VEGF, PDGF, bFGF, and TGF‐β. Additionally, a suspended co‐culture multicellular spheroid model revealed molecular‐level changes associated with extracellular matrix remodeling, cellular behaviors, inflammatory response, and pro‐angiogenic activity. Furthermore, KEGG pathway analysis identified the involvement of TGF‐β, IL‐17, Wnt, Notch, PI3K‐Akt, and MAPK pathways in regulating fibroblasts activity. These findings underscore the critical role of fibroblasts‐endothelial cells crosstalk in scar formation and provide potential targets for therapeutic intervention. Understanding the molecular mechanisms underlying this interplay holds promise for the development of innovative approaches to treat tissue injuries and diseases.

This study makes a significant contribution to the field of groundwater potential mapping (GWPM) by exploring the application of ensemble learning models (ELMs), specifically boosting ensemble models (BEMs), which have not been fully utilized in GWPM. By employing six ELMs (random forest, AdaBoost, XGBoost, CatBoost, GBDT, and LightGBM), along with Tree-structured Parzen Estimator in Luoning County, China, this study identifies key indicators (topographic position index, distance to rivers, and topographic wetness index) and demonstrates the superior model performance of XGBoost compared to other ELMs. Additionally, correlation analysis confirms the accuracy of XGBoost in predicting relationships between important indicators and groundwater potentials. Finally, the findings provide valuable insights for sustainable groundwater management strategies in Luoning County and emphasize the need for further exploration of ELMs, development of comprehensive performance evaluation and indicator systems, reduction of the inconsistencies between indicators and predication results and practical research to support future sustainable groundwater management.

Abstract Background Astragalus mongolicus Bunge is used in traditional Chinese medicine and is thus cultivated in bulk. The cultivation of A. mongolicus requires a large amount of nitrogen fertilizer, increasing the planting cost of medicinal materials and polluting the environment. Isolation and screening of plant growth-promoting rhizobacteria (PGPR) and exploring the nitrogen fixation potential of A. mongolicus rhizosphere microorganisms would effectively reduce the production cost of A. mongolicus. Results This study used A. mongolicus roots and rhizosphere soil samples from Longxi County of Gansu Province, Jingle County, and Hunyuan County of Shanxi Province, China, to isolate and identify nitrogen-fixing bacteria. Through nitrogen fixation efficiency test, single strain inoculation test, and plant growth-promoting characteristics, three strains, Bacillus sp. J1, Arthrobacter sp. J2, and Bacillus sp. G4 were selected from 86 strains of potential nitrogen-fixing bacteria, which were the most effective in promoting the A. mongolicus growth and increasing the nitrogen, phosphorus, and potassium content in plants. The antagonistic test showed that these bacteria could grow smoothly under the co-culture conditions. The J1, J2, and G4 strains were used in a mixed inoculum and found to enhance the biomass of A. mongolicus plants and the accumulation of the main medicinal components in the field experiment. Mixed bacterial agent inoculation also increased bacterial diversity and changed the structure of the bacterial community in rhizosphere soil. Meanwhile, the relative abundance of Proteobacteria increased significantly after inoculation, suggesting that Proteobacteria play an important role in plant growth promotion. Conclusions These findings indicate that specific and efficient PGPRs have a significant promoting effect on the growth of A. mongolicus, while also having a positive impact on the structure of the host rhizosphere bacteria community. This study provides a basis for developing a nitrogen-fixing bacterial fertilizer and improving the ecological planting efficiency of A. mongolicus.

Abstract Kagome lattice hosts a plethora of quantum states arising from the interplay of topology, spin-orbit coupling, and electron correlations. Here, we report symmetry-breaking electronic orders tunable by an applied magnetic field in a model Kagome magnet FeSn consisting of alternating stacks of two-dimensional Fe3Sn Kagome and Sn2 honeycomb layers. On the Fe3Sn layer terminated FeSn thin films epitaxially grown on SrTiO3(111) substrates, we observe trimerization of the Kagome lattice using scanning tunneling microscopy/spectroscopy, breaking its six-fold rotational symmetry while preserving the translational symmetry. Such a trimerized Kagome lattice shows an energy-dependent contrast reversal in dI/dV maps, which is significantly enhanced by bound states induced by Sn vacancy defects. This trimerized Kagome lattice also exhibits stripe modulations that are energy-dependent and tunable by an applied in-plane magnetic field, indicating symmetry-breaking nematicity from the entangled magnetic and charge degrees of freedom in antiferromagnet FeSn.

Fourier transform infrared spectroscopy (FTIR), as a non-destructive method, is widely used for the identification of compounds and the characterization of molecular structures. In order to characterize the changes in the chemical structure of charcoal under different combustion temperatures, and thus to provide a theoretical basis for the formation of fusinite in coal, plant samples (charcoal) from modern wildfires with different degrees of combustion were selected to quantify their chemical structures using FTIR. The results shown that the sample reflectance was positively proportional to the combustion temperature. The sample No. 1 with maximum combustion temperature had the highest degree of combustion, which was measured to reach 518 ℃. The aromatic structure was dominated by tri-substituted benzene rings in all samples except the highest combustion sample No. 1, but dehydrocondensation occurred with increasing combustion temperature, resulting in a reduction of tri-substituted content of benzene rings to 20.5%. The tetra-substituted content was elevated due to dehydroaromatization of the naphthenic structure, while the change in the penta-substituted content was related to the cyclization of aliphatic chain and the decarboxylation of benzene ring. With the increase of combustion temperature, the CC content gradually increased due to the formation of aromatic hydrocarbons or the shedding of molecular side chains after dehydrogenation of cycloalkanes, reached 32% in the sample No. 1. The content of C－O first decreased and then increased. In the sample No. 1, the content of alkyl ether and aryl ether was the lowest, and the content of phenolic hydroxyl group was the highest, which may be the generation of phenolic substances by thermal breakage of ether bond under high temperature combustion. The CO content increased and then decreased to as low as 5.6% in the sample No. 1, which was due to the poor stability of the bond. Due to the influence of combustion temperature, the content of fatty substances varied greatly, with an overall gradual increase in methylene content, a decrease in methyl group, and an increase in branching degree. There were five types of hydrogen bonds in the samples, with ether-oxygen hydrogen bonds predominating in samples affected by low temperature (>55%). Cyclic hydrogen bonds and hydroxyl-N hydrogen bonds appeared in sample No. 1, while the content of ether-oxygen hydrogen bonds decreased significantly to 13.2%, which was attributed to the reduction of oxygen-containing functional groups caused by the increasing temperature. Comparison of reflectance and FTIR characteristics of fusinite in coal revealed that the characteristics of fusinite (semifusinite) in coal were very similar to those of charcoal, which might be produced mainly by wildfires. These changes indicated the effect of combustion temperature on the chemical structure in charcoal, reflecting the process of organic molecular structure changed with temperature in charcoal, and providing a theoretical basis for the evolution of organic matter and the formation of fusinite in coal.

Background: Several COVID-19 vaccines were developed and approved in China. Of these, the BIBB-CorV and CoronaVac inactivated whole-virion vaccines were widely distributed in China and developing countries. However, the performance of the two vaccines in the real world has not been summarized. Methods: A living systematic review based on findings from ongoing post-licensure studies was conducted, applying standardized algorithms. Articles published between 1 May 2020 and 31 May 2022 in English and Chinese were searched for in Medline, Embase, WanFang Data, medRxiv, bioRxiv, arXiv, SSRN, and Research Square, using SARS-CoV-2, COVID-19, and vaccine as the MeSH terms. Studies with estimates of safety, immunogenicity, and effectiveness from receiving the BIBB-CorV or CoronaVac vaccine that met the predefined screening criteria underwent a full-text review. The Joanna Briggs Institute’s Critical Appraisal Checklist and the Cochrane risk of bias were used for assessment of the quality. A random-effects meta-regression model was applied to identify the potential impact factors on the vaccines’ effectiveness. Results: In total, 32578 articles were identified, of these, 770 studies underwent a full-text review. Eventually, 213 studies were included. The pooled occurrence of solicited and unsolicited adverse events after any dose of either vaccine varied between 10% and 40%. The top five commonly reported rare adverse events were immunization stress-related responses (211 cases, 50.0%), cutaneous responses (43 cases, 10.2%), acute neurological syndrome (39 cases, 9.2%), anaphylaxis (17 cases, 4.0%), and acute stroke (16 cases, 3.8%). The majority (83.3%) recovered or were relieved within several days. The peak neutralization titers against the ancestral strain was found within 1 month after the completion of the primary series of either vaccine, with a GMT (geometric mean titer) of 43.7 (95% CI: 23.2–82.4), followed by a dramatic decrease within 3 months. At Month 12, the GMT was 4.1 (95% CI: 3.8–4.4). Homologous boosting could restore humoral immunity, while heterologous boosting elicited around sixfold higher neutralization titers in comparison with homologous boosting. The effectiveness of receiving either vaccine against death and severe disease was around 85% for both shortly after the primary series. At Month 12, the protection against death did not decline, while the protection against severe disease decreased to ~75%. Conclusions: Both the BIBP-CorV and CoronaVac inactivated vaccines are safe. Sustained vaccine effectiveness against death was determined 12 months after the primary series, although protection against severe disease decreased slightly over time. A booster dose could strengthen the waning effectiveness; however, the duration of the incremental effectiveness and the additional benefit provided by a heterologous booster need to be studied.

The No. 9 coal of Yunjialing Coal Mine in Handan Coalfield, which is subject to obvious magmatic intrusion, is taken as the research object. Optical microscope observation, electron probe energy spectrometry (EPMA-EDS), X-ray diffractometer (XRD), X-ray fluorescence spectrometry (XRF) and other analytical tests were used to analyze the enrichment characteristics of whole sulfur, sulfur forms and minerals, to study the occurrence of sulfur and pyrite in the coals, and to explore the sources of different types of pyrite. The results show that the No. 9 coal of Yunjialing Coal Mine in Handan Coalfield is a high-sulfur coal (0.61%～7.12%), sulfide sulfur is the main form of sulfur in the coal (1.18%～4.90%), followed by organic sulfur (0.56%～2.16%) with a little sulphate sulfur (0.01%～0.06%). The No. 9 coal of Yunhailing coal mine was deposited in the transitional environment of sea and land phases, and seawater intrusion provided abundant sulfur source for the No. 9 coal seam, the gas-liquid materials brought about by neutral magmatism during the Yanshan period elevate the total sulfur content in the No. 9 coal of the Yunjialing Caol Mine, especially the total sulfur content of the upper coal plies are significantly higher than the total sulfur content of the whole coal seam. The microscopic occurrence of pyrite in the No. 9 coal mainly includes massive pyrite, disseminated pyrite and fissure-filled pyrite, and is characterized by multi-stage evolution. Massive pyrite is mainly formed in the early diagenetic stage, the high temperature and gas-liquid materials brought about by neutral magmatism during the Yanshan period modified the morphology of pyrite in the coal, resulting in the activation and recrystallization of pyrite in the coal into a massive fraction. Inorganic sulfur from the high-temperature-affected portion of the pyrite diffused into the surrounding coal body and sequestered as organic sulfur, increasing the organic sulfur content of the upper coal plies.

Abstract Background The aim of study was to evaluate survival outcome and limb function in cancer patients with proximal limbs metastasis. Associated factors on survival outcome and limb function were identified. The comparative analysis between intramedullary nailing and prosthesis surgery in cancer patients with proximal limb metastasis was performed. Methods In this five-center retrospective study, patients diagnosed with limbs metastasis were collected. Descriptive statistics was used and log-rank test was performed to analyze the survival in subgroups. The Cox proportional hazards regression analysis was performed to identify the independent prognostic factors. The Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate limb function after surgery, and t test or analysis of variance (ANOVA) was utilized in subgroup analysis. Results A total of 316 patients with limb metastasis were included with mean age at 61.0 years. The most common primary tumor was breast, followed by renal cancer and lung cancer. The median overall survival was 24.0 months and the 1-, 3- and 5-year survival rates were 86.9%, 34.7% and 6.8%, respectively. Primary tumor type, visceral metastasis and chemotherapy were proved to be the independent prognostic factors. The mean Musculoskeletal Tumor Society (MSTS) score was 20.5, significant difference was observed in subgroup of solitary/multiple bone metastasis, with/without pathological fracture, and type of surgery. Conclusion The present study concluded that primary tumor type, visceral metastasis and chemotherapy were three factors affecting the survival of patients. Compared with intramedullary nailing, the patients underwent prosthesis surgery showed better limb function, this procedure should be encouraged in patients with indication.

Abstract Covering array generation (CAG) is the key research problem in combinatorial testing and is an NP‐complete problem. With the increasing complexity of software under test and the need for higher interaction covering strength t, the techniques for constructing high‐strength covering arrays are expected. This paper presents a hybrid heuristic memetic algorithm named QSSMA for high‐strength CAG problem. The sub‐optimal solution acceptance rate is introduced to generate multiple test cases after each iteration to improve the efficiency of constructing high‐covering strength test suites. The QSSMA method could successfully build high‐strength test suites for some instances where t up to 15 within one day cutoff time and report five new best test suite size records. Extensive experiments demonstrate that QSSMA is a competitive method compared to state‐of‐the‐art methods.

Aiming at the problem that the existing sensor network trust evaluation model could not be directly applied to the new power system distributed home photovoltaic collection scenario, which was difficult to meet the require-ments of strong computing power and high defense power of the new power system, a distributed dynamic trust evaluation model based on multi-index detection was proposed.Firstly, the communication trust evaluation based on Bayes was carried out according to the historical interaction of terminal acquisition nodes.Then, the currently col-lected data was evaluated by perceptual trust based on its historical data support degree and regional trust based on probability density.Finally, the entropy weight method was used to decentralize each trust module’s values dynamically.The node activeness and double reward and punishment mechanism were introduced to calculate the comprehensive trust value and realize the dynamic update.The experimental results show that the four levels of the trust evaluation model are suitable for the new power system environment and can be used to detect the distributed in 20 round period of household photovoltaic power generation collection given the signal in the scene, achieve dynamic and accurate trust evaluation of abnormal nodes in the case of physical environment factors, equipment quality factors, human misoperation and malicious intrusion.

Pod dehiscence brings much loss for modern agricultural production, and multiple pod dehiscence components have been identified in many plant species. However, the pod dehiscence regulation factors in soybean are limited. In this study, we investigate the function of GmDIR26, a close homologues gene of pod dehiscence genes GmPdh1, PvPdh1, and CaPdh1, in the regulation of pod dehiscence in soybean. The secondary and tertiary structure analysis reveals that GmDIR26 protein has a similar structure with GmPdh1, PvPdh1, and CaPdh1 proteins. Synteny analysis of soybean and chickpea genomes shows that the genomic region surrounding GmDIR26 and CaPdh1 might be evolved from the same ancestor, and these two genes might have similar function. GmDIR26 shows an increased expression pattern during pod development and reaches a peak at beginning seed stage. Meanwhile, GmDIR26 exhibits high expression levels in dorsal suture and pod wall, but low expression pattern in ventral suture. In addition, GmDIR26 shows higher expression levels in pod dehiscence genotype than that in pod indehiscence accessions. Overexpression of GmDIR26 in soybean increases pod dehiscence in transgenic plants, of which the lignin layer in inner sclerenchyma pods is thicker and looser. The expression levels of several pod dehiscence genes are altered. Our study provides important information for further modification of pod dehiscence resistance soybean and characterization of soybean pod dehiscence regulation network.

Besides exhibiting excellent capabilities such as energy absorption, phase-transforming metamaterials offer a vast design space for achieving nonlinear constitutive relations. This is facilitated by switching between different patterns under deformation. However, the related inverse design problem is quite challenging, due to the lack of appropriate mathematical formulation and the convergence issue in the post-buckling analysis of intermediate designs. In this work, periodic unit cells are explicitly described by the moving morphable voids method and effectively analyzed by eliminating the degrees of freedom in void regions. Furthermore, by exploring the Pareto frontiers between error and cost, an inverse design formulation is proposed for unit cells. This formulation aims to achieve a prescribed constitutive curve and is validated through numerical examples and experimental results. The design approach presented here can be extended to the inverse design of other types of mechanical metamaterials with prescribed nonlinear effective properties.

A new class of 2-acetyl-1,3-diacyl-sn-glycerols (sn-2-acTAG) was found in the seed oil of Polygala previously. Its structure is very similar to sn-1,3-DAG, which has effect of preventing and treating hyperlipidemia and other diseases. In this study, sn-2-acTAG was enriched and confirmed, the safety and the hypolipidemic activity was assessed. In addition the mechanism of action was investigated. Our study indicated that a diet containing 20% sn-2-acTAG or lower was not toxic to SD rats. Compared to the soybean oil group, sn-2-acTAG could lower the total cholesterol, triglyceride, and high-density lipoprotein cholesterol levels, as well as rise the level of high-density lipoprotein cholesterol. Sn-2-acTAG could regulate the expression of proinflammatory factors to ameliorate hyperlipidemia. In conclusion, sn-2-acTAG has for the first time been found to significantly ameliorate hyperlipidemia in the high-fat diet rat. This study will provide a strong theoretical support for the efficient development and application of Polygala seed oil.

Abstract Introduction The HIV Prevention Trials Network (HPTN) 074 study demonstrated a positive effect of an integrated systems navigation and psychosocial counseling intervention on HIV treatment initiation, viral suppression, medication assisted treatment (MAT) enrollment, and risk of death among people who inject drugs (PWID). In this sub-study, we analyzed the incidence, causes, and predictors of death among HIV-infected and uninfected participants. Methods The HPTN 074 randomized clinical trial was conducted in Indonesia, Ukraine, and Vietnam. HIV-infected PWID with unsuppressed viral load (indexes) were recruited together with at least one of their HIV-negative injection partners. Indexes were randomized in a 1:3 ratio to the intervention or standard of care. Results The trial enrolled 502 index and 806 partner participants. Overall, 13% (66/502) of indexes and 3% (19/806) of partners died during follow-up (crude mortality rates 10.4 [95% CI 8.1–13.3] and 2.1 [1.3–3.3], respectively). These mortality rates were for indexes nearly 30 times and for partners 6 times higher than expected in a population of the same country, age, and gender (standardized mortality ratios 30.7 [23.7–39.0] and 5.8 [3.5–9.1], respectively). HIV-related causes, including a recent CD4

Abstract Background Dyslipidaemia is key in the development of coronary heart disease (CHD) in patients with diabetes mellitus (DM). Accumulated evidence supports that diabetic nephropathy increases the mortality risk of patients with CHD, while the influence of diabetic dyslipidaemia on renal damage in patients with DM and CHD remains unknown. Moreover, recent data indicate that postprandial dyslipidaemia has predictive value in terms of CHD prognosis, especially in patients with DM. The study aimed to determine the relationship of triglyceride-rich lipoproteins (TRLs) after daily Chinese breakfast on systemic inflammation and early renal damage in Chinese patients with DM and SCAD. Methods Patients with DM diagnosed with SCAD while in the Department of Cardiology of Shengjing Hospital from September 2016 to February 2017 were enrolled in this study. Fasting and 4-h postprandial blood lipids, fasting blood glucose, glycated haemoglobin, urinary albumin-to-creatinine ratio (UACR), serum interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) concentrations, and other parameters were measured. Fasting and postprandial blood lipid profiles and inflammatory cytokines were analysed using a paired t-test. The association between variables was analysed using Pearson or Spearman bivariate analysis. P

Mitochondrial DNA (mtDNA) somatic mutations play important roles in the initiation and progression of cancer. Although next‐generation sequencing (NGS) of paired tumor and control samples has become a common practice to identify tumor‐specific mtDNA mutations, the unique nature of mtDNA and NGS‐associated sequencing bias could cause false‐positive/‐negative somatic mutation calling. Additionally, there are clinical scenarios where matched control tissues are unavailable for comparison. Therefore, a novel approach for accurately identifying somatic mtDNA variants is greatly needed, particularly in the absence of matched controls. In this study, the ground truth mtDNA variants orthogonally validated by triple‐paired tumor, adjacent nontumor, and blood samples were used to develop mitoSomatic, a random forest‐based machine learning tool. We demonstrated that mitoSomatic achieved area under the curve (AUC) values over 0.99 for identifying somatic mtDNA variants without paired control in three tumor types. In addition, mitoSomatic was also applicable in nontumor tissues such as adjacent nontumor and blood samples, suggesting the flexibility of mitoSomatic's classification capability. Furthermore, analysis of triple‐paired samples identified a small group of variants with uncertain somatic/germline origin, whereas application of mitoSomatic significantly facilitated the prediction of their possible source. Finally, a control‐free evaluation of the public pan‐cancer NGS dataset with mitoSomatic revealed a substantial number of variants that were probably misclassified by conventional tumor‐control comparison, further emphasizing the usefulness of mitoSomatic in application. Taken together, our study demonstrates that mitoSomatic is valuable for accurately identifying somatic mtDNA variants in mtDNA NGS data without paired controls, applicable for both tumor and nontumor tissues.

Abstract Background The etiopathogenesis of idiopathic non-cirrhotic portal hypertension (INCPH) is so far poorly understood. Altered immunity, blood diseases, infections, congenital defects and drug exposure have been documented in a part of patients with INCPH owing to increased recognition of the disorder in patients with HIV, or various haematological disorders or autoimmune diseases. We aim to discuss the possible etiopathogenesis of INCPH. Case presentation We reported that a patient with intestinal infection of T. Marneffei and hyper-IgE syndrome, a group of rare primary immunodeficiency disorders, was finally diagnosed with INCPH for gastroesophageal variceal bleeding. The diagnosis was mainly based on histopathological features. Transjugular intrahepatic portosystemic shunt was performed and there was no recurrence of melena during the six-month follow-up. Conclusion In the context of immunodeficiency, INCPH may associated with intestinal infections. Thus, screening for enterogenic infection and immunological disorders in patients with unexplained portal hypertension is necessary.

An 8-week feeding trial investigated the optimum dietary vitamin K3 requirements of largemouth bass. A total of 600 healthy fish (12.96 ± 0.07 g) were fed diets containing varying levels of vitamin K3 at 0.78 (K0), 5.80 (K5), 10.82 (K10), 15.84 (K15), and 20.85 (K20) mg/kg with four replicates per level. Results showed that dietary vitamin K3 enhanced growth, with weight gain rate and specific growth rate in K15 trials significantly higher than K0 trials (P 0.05). However, the supplementation of vitamin K3 significantly contributed to calcium accumulation in muscle tissues and vertebrae (P 0.05). The antioxidant capacity was improved with the addition of vitamin K3, which was inconsistent with the changes in malondialdehyde and MK-4 (a form of menaquinone) within liver and serum, suggesting that the toxicity of excessive artificial vitamin K3 may account for this difference. Using regression analysis, the appropriate dietary vitamin K3 levels within a largemouth bass diet was determined to be in the range of 9.93–15.22 mg/kg, which will provide a reference for the preparation of vitamin premix and artificial diet for largemouth bass.

Bacterial antimicrobial resistance (AMR) poses a significant global public health challenge. The escalation of AMR is primarily attributed to the horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs), often facilitated by plasmids. This underscores the critical need for a comprehensive understanding of the resistance mechanisms and transmission dynamics of these plasmids. In this study, we utilized in vitro drug sensitivity testing, conjugation transfer assays, and whole-genome sequencing to investigate the resistance mechanism of an extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolate, MAS152. We specifically focused on analyzing the drug-resistant plasmid pMAS152 it harbors and its potential for widespread dissemination. Bioinformatics analysis revealed that MAS152 carries a distinct IncpP-2A plasmid, pMAS152, characterized by a 44.8 kb multidrug resistance (MDR) region. This region houses a 16S rRNA methyltransferase (16S-RMTase) gene, rmtB, conferring high-level resistance to aminoglycoside antibiotics. Notably, this region also contains an extended-spectrum β-Lactamase (ESBL) gene, blaPER-1, and an efflux pump operon, tmexCD-oprJ, which mediate resistance to β-Lactams and quinolone antibiotics, respectively. Such a combination of ARGs, unprecedented in reported plasmids, could significantly undermine the effectiveness of first-line antibiotics in treating P. aeruginosa infections. Investigation into the genetic environment of the MDR region suggests that Tn2 and IS91 elements may be instrumental in the horizontal transfer of rmtB. Additionally, a complex Class I integron with an ISCR1 structure, along with TnAs1, seems to facilitate the horizontal transfer of blaPER-1. The conjugation transfer assay, coupled with the annotation of conjugation-related genes and phylogenetic analysis, indicates that the plasmid pMAS152 functions as a conjugative plasmid, with other genus Pseudomonas species as potential hosts. Our findings provide vital insights into the resistance mechanisms and transmission potential of the XDR P. aeruginosa isolate MAS152, underlining the urgent need for novel strategies to combat the spread of AMR. This study highlights the complex interplay of genetic elements contributing to antibiotic resistance and underscores the importance of continuous surveillance of emerging ARGs in clinical isolates.

The measurements derived from damaged conditions are difficult to acquire in actual structures, which limits the applicability of supervised damage detection methods. In this study, an unsupervised damage detection method that leverages an improved generative adversarial network (IGAN) and cloud model (CM) is proposed. This method only needs the data in the healthy state of the structure for model training, which can solve the above problems. Firstly, an IGAN model is established, which uses the encoder-decoder-encoder generative network to encode, reconstruct and re-encode the structural response in healthy state. The essential features hidden in complex data are learned by minimizing the distance between the real response and the reconstructed response, and the distance between the latent vectors obtained after two different encodings. During the test phase, when unknown state data is input into the model, the differences of the latent features of the two different codes can be used to preliminarily judge whether the structure is damaged. In addition, CM theory is used to further quantify structural damage and solve the problem of damage misjudgment caused by measurement noise, model parameters, feature selection, and other uncertain factors. The effectiveness of the proposed damage detection method is verified by Phase I IASC-ASCE benchmark structure and a bridge health monitoring benchmark model. The results prove that the proposed method can accurately detect the damage that has occurred.

Abstract While the terrestrial base stations (TBSs) in the fifth‐generation (5G) network provide high throughput for the conventional terrestrial users (TUs), it is still challenging for the network to support massive TUs and unmanned aerial vehicles (UAVs) simultaneously due to the complicated air–ground channel and severe interference. In this paper, the deployment of a high‐altitude platform (HAP) as a supplement for the terrestrial networks, in which the HAP and TBSs serve TUs and UAVs simultaneously in a joint manner, is studied. The novel network has two challenges. First, the deployment of the HAP, which is a new degree of freedom, should be optimized considering the terrestrial network. Second, the channel of the joint HAP and TBS network that serves multiple TUs and UAVs concurrently is complicated, and the resource allocation of the network should be designed. To tackle the above two challenges, a joint resource allocation and HAP deployment problem are formulated, and a gradient‐and‐matching‐based algorithm is proposed to solve it efficiently. Simulation results show that the HAP and the proposed algorithm enhance the sum‐rate of the network by over 30%, and the average data rate of both the TUs and the UAVs can be effectively improved.

Abstract Background According to reports, between 30 and 40 percent of extrapulmonary tuberculosis (EPTB) cases are caused by urinary tract tuberculosis (UTB). It is critical to identify UTB quickly since it frequently precedes delayed medical attention, which can have detrimental effects. This study examined the use of Xpert MTB/RIF, a PCR test that can detect MTB as well as resistance to an important drug, rifampicin (RIF), in UTB particularly, for the early identification of UTB. Methods 180 participants with clinically presumptive UTB whose urine samples were chosen for urine sediment smear, culture, Xpert MTB/RIF, and TB-DNA testing at Henan Chest Hospital between January 2019 and July 2022. Evaluation of test performance using Composite Reference Standards (CRSs). We studied and compared the positivity rate for various tests using the t-test. The effectiveness of smear, culture, Xpert MTB/RIF, and TB-DNA was assessed using McNemar test. Results In this subject, a total of 108 participants were diagnosed with UTB, and the positivity rate was 67.1%. Compared with CRS, the positivity rate of Xpert MTB/RIF, smear, culture, and TB-DNA was 29.69% (19/64, P 0.05), and 18.75% (6/32, P 0.05), and 26.7% (4/15, P > 0.05) for TB-DNA, respectively, compared to smear negative. Xpert MTB/RIF assay specificity was significant for culture and TB-DNA (53.6% vs. 25%, P