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The genus Nodularia poses a significant challenge to traditional species classification and identification due to its highly convergent and variable shells, rendering it one of the most intricate groups within the family Unionidae. Fortunately, significant progress has been made by researchers in recent years regarding the species validity and the phylogeny of this group based on molecular data. However, the inadequate exploration of regional constraints and inherent limitations in research methodologies remains a crucial factor contributing to the underestimation of species diversity. In this study, a new species of freshwater mussel from the Qingshui River in Nanning City, Guangxi Province, China, Nodularia guiensis sp. nov., is described based on shell morphology, anatomical characters, and molecular phylogenetics. Mitochondrial phylogenomic analyses reveal the following phylogenetic relationships: (((Nodularia hanensis + Nodularia micheloti) + Nodularia dorri) + (Nodularia breviconcha + (Nodularia huana + (Nodularia fusiformans + (Nodularia guiensis sp. nov. + ((Nodularia nuxpersicae + Nodularia nipponensis) + (Nodularia dualobtusus + Nodularia douglasiae))))))). The discovery of this new taxon further enhances the diversity level within the genus Nodularia in China and also highlights the necessity for comprehensive surveys of unexplored regions in order to potentially unveil additional new taxa in the future.

Abstract Mecoptera is a small relict order of insects within the Holometabola. Panorpidae is the most speciose family in Mecoptera. They are also known as scorpion flies due to the enlarged and upward recurved male genital bulb. Panorpa liui Hua, 1997, a member of Panorpidae, is a bivoltine species of seasonal color polyphenism in the lowland plain of northeastern China. In this study, we applied PacBio HiFi and Hi–C sequencing technologies to generate a chromosome-level genome reference of P. liui. The assembled genome is 678.26 Mbp in size, with 91.3% being anchored onto 23 pseudo–chromosomes. Benchmarking Universal Single–Copy Orthologs (BUSCO) estimation reveals the completeness of this assembly as 95.1%. By integrating full-length transcriptome and homologs of related species, we generated full annotation of this assembly, yielding a total of 15,960 protein–coding genes, of these, 15,892 genes were anchored on the 23 chromosomes. The high-quality genome provides critical genomic resources for population genetics and phylogenetic research on Mecoptera. It also offers valuable information for exploring the mechanisms underlying seasonal color polymorphism.

Abstract Background Neutropenia frequently presents as a hematological manifestation among people living with HIV/AIDS (PLWHA). This study explores the factors associated with neutropenia in PLWHA and its prognostic significance. Methods We conducted a retrospective case-control study of the clinical data from 780 cases of individuals living with HIV/AIDS, who were admitted to Zhongnan Hospital of Wuhan University over the period from January 2016 to September 2020. We categorized the patients into two different groups based on absolute neutrophil Count (ANC): neutropenia group (ANC

Abstract Background The most common malignant type of kidney cancer is clear cell renal cell carcinoma (ccRCC). The expression levels of hyaluronan-mediated motility receptor (HMMR) in many tumor types are significantly elevated. HMMR is closely associated with tumor-related progression, treatment resistance, and poor prognosis, and has yet to be fully investigated in terms of its expression patterns and molecular mechanisms of action in ccRCC. Further research is imperative to elucidate these aspects. Methods We used The Cancer Genome Atlas (TCGA) database to preliminarily investigate HMMR expression and function in ccRCC and the data for 19 samples from the NCBI GEO database (GSE207493) for single-cell analysis. We assessed the differential expression level of HMMR between ccRCC cancerous tissues and their matched non-tumor tissues. Subsequently, a series of in vivo and in vitro experiments were designed to elucidate the biological function of HMMR in ccRCC, including Transwell assays, CCK-8 assays, clone formation assays and subcutaneous xenograft experiments in nude mice. Through bioinformatics analysis, we identified potential microRNAs (miRNAs) that may regulate HMMR, as well as the possible signaling pathways involved. Finally, we conducted a series of cellular functional experiments to validate our hypotheses regarding the HMMR axis. Results HMMR expression was significantly up-regulated in tumor tissues of ccRCC patients, and elevated HMMR expression level showed a strong correlation with ccRCC progression and adverse prognoses of patients. Knocking down HMMR inhibited the proliferative and migratory abilities of ccRCC cells, while its overexpression amplified these oncogenic properties. In nude mice model, reduced HMMR expression inhibited ccRCC tumor proliferation in vivo. Furthermore, overexpression of an upstream transcriptional regulator, miR-9-5p, effectively downregulated HMMR expression and thus impeded ccRCC cells proliferation and migration. HMMR might influence ccRCC growth via the Epithelial-Mesenchymal Transition (EMT) pathway and the Janus Kinase 1/Signal Transducer and Activator of Transcription 1 (JAK1/STAT1) pathway. Conclusions HMMR is overexpressed in ccRCC, and there is a significant link between high HMMR expression and tumor progression, as well as poor patient prognosis. Specifically, HMMR could be targeted and inhibited by miR-9-5p and might modulate the tumorigenesis and progression of ccRCC through both EMT and JAK1/STAT1 signaling pathway.

Abstract Background Amidst the escalating loss of global biodiversity, freshwater mussels (family Unionidae) have become one of the most imperiled animal groups. Acquiring more biological and phylogenetic information on understudied taxa constitutes a pivotal aspect of conservation biology. Consequently, a comprehensive examination was conducted on Koreosolenaia, Parvasolenaia, and Sinosolenaia from China encompassing morphology, anatomy, distribution, and molecular systematics to provide theoretical support for future species endangerment assessments and biodiversity conservation. Results The shell characteristics of Koreosolenaia, Parvasolenaia, and Sinosolenaia were clearly distinct, and the soft-body morphology could also be easily distinguished from each other. The papillae of the incurrent aperture of Sinosolenaia iridinea, Sinosolenaia recognita, and Sinosolenaia oleivora, which were previously described as difficult, exhibited significant variations that could be utilized for species diagnosis. Furthermore, both incurrent and excurrent apertures of the Sinosolenaia species had small cysts on their dorsal surfaces which may be unique to this particular group. Comparative analysis of six mitochondrial genomes (Parvasolenaia rivularis, Koreosolenaia sitgyensis, Sinosolenaia iridinea, Sinosolenaia recognita, Sinosolenaia carinata, and Sinosolenaia oleivora) revealed a completely consistent gene arrangement pattern. Additionally, there was a high consistency in nucleotide base content and skewness, amino acid usage, and relative synonymous codon usage among the six complete mitochondrial genomes. Mitochondrial phylogenomics of these genomes with additional taxa within Gonideinae robustly supported the generic relationships as follows: (Inversidens + ((Microcondylaea + Sinosolenaia) + (Parvasolenaia + (Koreosolenaia + (Ptychorhynchus + (Postolata + Cosmopseudodon)))))). Conclusions The present study provided significant data on the shell morphology and soft-body anatomy of Koreosolenaia, Parvasolenaia, and Sinosolenaia, thereby clarifying the diagnostic characteristics for these challenging taxa. Additionally, we established a robust phylogenetic framework at both the generic and species levels based on mitochondrial genomics.

Abstract Objective To assess seizure outcomes, prognostic factors, and developmental changes in children undergoing total posterior quadrant disconnection (PQD) for drug‐resistant epilepsy (DRE). Methods We conducted a retrospective analysis of the clinical data of children with DRE who underwent total PQD surgery. The study focused on Engel's classification for seizure outcomes, exploring correlation of preoperative data and surgical effectiveness, and predictors of seizure prognosis. It involved a comparative analysis of developmental levels pre‐ and 3 months postoperatively using Griffiths Mental Development Scales‐China (GMDS‐C), and the correlation between clinical characteristics and GMDS‐C results. Results Out of 61 pediatric patients, 70.5% showed no seizure recurrence postoperatively. In the univariate analysis, interictal electroencephalogram (EEG), magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG‐PET), and acute postoperative seizure (APOS) were significantly related to surgical prognosis. In multivariate analysis, interictal EEG and APOS were identified as predictors of seizure prognosis. Survival analysis indicated significant associations between MRI, interictal EEG, FDG‐PET, APOS and postoperative seizure occurrence. Preoperative GMDS‐C levels were significantly correlated with epilepsy duration, seizure frequency, interictal EEG, and FDG‐PET. GMDS‐C scores improved postoperatively, while developmental quotients remained stable. Significance For patients with structural abnormalities in the entire posterior quadrant, thorough preoperative assessment and timely total PQD surgery can effectively control seizures without causing neurological development deterioration. APOS and interictal EEG abnormalities beyond the posterior quadrant are predictors for seizure prognosis but should not be deemed contraindications for surgery. Plain Language Summary Due to lack of analysis on pediatric total PQD cases, 61 pediatric patients who underwent total PQD surgery were retrospectively enrolled. Seizure and development results were collected and analyzed as dependent variables. The study found that 70.5% of patients were seizure‐free and showed development improvement, with no deaths or severe complications reported. Prognosis predictors included APOS and interictal EEG abnormalities beyond the posterior quadrant.

Abstract Human umbilical cord mesenchymal stem cells (hUC-MSCs) have shown potential as a therapeutic option for lupus nephritis (LN), particularly in patients refractory to conventional treatments. Despite extensive translational research on MSCs, the precise mechanisms by which MSCs migrate to the kidney and restore renal function remain incompletely understood. Here, we aim to clarify the spatiotemporal characteristics of hUC-MSC migration into LN kidneys and their interactions with host cells in microenvironment. This study elucidates that the migration of hUC-MSCs to the LN kidney is driven by elevated levels of CXCL10, predominantly produced by glomerular vascular endothelial cells through the IFN-γ/IRF1-KPNA4 pathway. Interestingly, the blockade of CXCL10-CXCR3 axis impedes the migration of hUC-MSCs to LN kidney and negatively impacts therapeutic outcomes. Single cell-RNA sequencing analysis underscores the importance of this axis in mediating the regulatory effects of hUC-MSCs on the renal immune environment. Furthermore, hUC-MSCs have been observed to induce and secrete interleukin 4 inducible gene 1 (IL4I1) in response to the microenvironment of LN kidney, thereby suppressing Th1 cells. Genetically ablating IL4I1 in hUC-MSCs abolishes their therapeutic effects and prevents the inhibition of CXCR3+ Th1 cell infiltration into LN kidneys. This study provides valuable insights into the significant involvement of CXCL10-CXCR3 axis in hUC-MSC migration to the LN kidneys and the subsequent remodeling of renal immune microenvironment. Regulating the CXCL10-CXCR3 axis and IL4I1 secretion may be developed as a novel therapeutic strategy to improve treatment outcomes of LN.

Abstract At present, the characteristics of double-hit multiple myeloma (DHMM) are unknown. We retrospectively analyzed the clinical data from 433 new diagnosed MM patients and found that DHMM have a higher β2-MG level and percentage of bone marrow plasma cell. Cox regression analysis showed that the prognosis of DHMM was not limited by clinical indicators. The abnormal proliferation of bone marrow in DHMM is obvious, and the proportion of poorly differentiated plasma cell is high. By collecting specimens from our center and performing flow cytometry to analyze the immunophenotypic and functional characteristics of lymphocyte subpopulations, we found that DHMM had a higher ratio of Tregs cells, and the proportion of iTregs cells was also significantly higher than non-DHMM (P

Abstract Transition metal carbide shows excellent performance in selective hydrogenation of acetylene, however, the carburization of Pd-based intermetallic compounds remains infeasible. Here we report the successful synthesis of an unprecedented Pd3ZnCx intermetallic carbide, via co-infiltration of zinc and carbon in one-step carburization by syngas. Utilizing state-of-the-art in situ characterizations and theoretical calculation, we unveil the dynamic evolution of Pd3ZnCx during carburization, forming a Pd3Zn like cubic phase carbide structure. A unique transitional state (Pdt) with low content of Zn/C co-infiltration is clearly identified facilitating phase transition and sustain incorporation of carbon and zinc at elevated temperatures. The Pd3ZnCx carbide shows by far the best catalytic performance in the selective hydrogenation of acetylene with a high selectivity (>90%) even at a high H2/C2H2 ratio. Our results therefore provide a co-infiltration strategy and dynamic insights for the one-step synthesis of Pd based intermetallic carbides, towards high-performance intermetallic compound for selective hydrogenation of acetylene.

Abstract Objective Gastric cancer (GC) is one of the most prevalent malignant tumors of the digestive system. The advanced metastasis of gastric cancer severely limits the conventional approaches for its treatment, while certain traditional Chinese medicinal compounds have been reported to possess promising abilities in inhibiting tumor metastasis. Such as Poria (PA), known as Fu Ling in Chinese, is a commonly used traditional Chinese medicinal herb derived from Poria cocos, a fungus belonging to the polyporaceae family. Methods The proliferation capacity of cells was measured using the MTT assay, while the invasion and migration abilities of cells after treatment with different concentrations of PA were evaluated through wound healing assay and Transwell assay. The differential expression of mRNA was analyzed using qPCR. The in vivo growth of tumors was assessed by subcutaneous tumor formation in mice. Results Both in vivo and in vitro experiments have demonstrated that PA significantly inhibits the proliferation of GC. Moreover, in vitro experiments have revealed that PA not only suppresses the invasion and migration of GC cells but also reverses TNF-β-induced EMT. Further experiments have revealed that PA inhibits cell invasion, migration and EMT by inducing ferroptosis in GC cells. Conclusion In brief, the present study shows that PA inhibits tumor metastasis by inducing ferroptosis in GC cells. Our findings suggest that PA may have therapeutic potential in GC.

Abstract Retinal neovascularization (RNV) disease is one of the leading causes of blindness, yet the molecular underpinnings of this condition are not well understood. To delve into the critical aspects of cell-mediated angiogenesis, we analyzed our previously published single-cell data. Our analysis revealed that retinal pigment epithelium (RPE) cells serve a crucial promotional function in angiogenesis. RPE cells were regulated by N6-methyladenosine (m6A). Next, we detected several critical m6A methylase in hypoxic ARPE-19 cells and in oxygen-induced retinopathy (OIR) mice, our results revealed a significant decrease in the level of methyltransferase like 3 (METTL3). METTL3 specific inhibitor STM2457 intravitreal injection or METTL3 conditional knockout mice both showed a significantly reduced neovascularization area of retina. Additionally, the angiogenesis-related abilities of human retinal endothelial cells (HRECs) were diminished after co-cultured with ARPE-19 treated with STM2457 or sh-METTL3 in vitro. Furthermore, through the integration of Methylated RNA immunoprecipitation (MeRIP) sequencing and RNA sequencing, we discovered that the metabolic enzyme quinolinate phosphoribosyltransferase (QPRT) was directly modified by METTL3 and recognized by the YTH N6-methyladenosine RNA binding protein C1 (YTHDC1). Moreover, after over-expressing QPRT, the angiogenic abilities of HRECs were improved through the phosphorylated phosphatidylinositol-3-kinase (p-PI3K)/ phosphorylated threonine kinase (p-AKT) pathway. Collectively, our study provided a novel therapeutic target for retinal angiogenesis.

Abstract Mesenchymal–epithelial transition (MET) exon 14 (METex14) skipping mutation is a rare (3%–4%) driver mutation in non‐small cell lung cancer (NSCLC). Tepotinib, a selective MET inhibitor, has shown promise in treating METex14 skipping‐mutated NSCLC. However, its feasibility for perioperative application remains unclear. This report describes a 60‐year‐old man with stage IIIA (cT2N2M0) lung adenocarcinoma harboring a METex14 skipping mutation. After initial treatment with savolitinib was discontinued due to grade 4 transaminitis, the patient was switched to tepotinib, resulting in significant tumor regression. Six months later, further shrinkage was observed, and surgery revealed remarkable pathological response with no residual tumor in lymph nodes (ypT2N0M0, IB). Postoperative tepotinib continued, with no relapse at 6‐month follow‐up. This case highlights the potential of tepotinib as neoadjuvant therapy for resectable METex14 skipping‐mutated NSCLC, warranting further clinical trials.

Abstract Background Lavandula angustifolia holds importance as an aromatic plant with extensive applications spanning the fragrance, perfume, cosmetics, aromatherapy, and spa sectors. Beyond its aesthetic and sensory applications, this plant offers medicinal benefits as a natural herbal remedy and finds use in household cleaning products. While extensive genomic data, inclusive of plastid and nuclear genomes, are available for this species, researchers have yet to characterize its mitochondrial genome. This gap in knowledge hampers deeper understanding of the genome organization and its evolutionary significance. Results Through the course of this study, we successfully assembled and annotated the mitochondrial genome of L. angustifolia, marking a first in this domain. This assembled genome encompasses 61 genes, which comprise 34 protein-coding genes, 24 transfer RNA genes, and three ribosomal RNA genes. We identified a chloroplast sequence insertion into the mitogenome, which spans a length of 10,645 bp, accounting for 2.94% of the mitogenome size. Within these inserted sequences, there are seven intact tRNA genes (trnH-GUG, trnW-CCA, trnD-GUC, trnS-GGA, trnN-GUU, trnT-GGU, trnP-UGG) and four complete protein-coding genes (psbA, rps15, petL, petG) of chloroplast derivation. Additional discoveries include 88 microsatellites, 15 tandem repeats, 74 palindromic repeats, and 87 forward long repeats. An RNA editing analysis highlighted an elevated count of editing sites in the cytochrome c oxidase genes, notably ccmB with 34 editing sites, ccmFN with 32, and ccmC with 29. All protein-coding genes showed evidence of cytidine-to-uracil conversion. A phylogenetic analysis, utilizing common protein-coding genes from 23 Lamiales species, yielded a tree with consistent topology, supported by high confidence values. Conclusions Analysis of the current mitogenome resource revealed its typical circular genome structure. Notably, sequences originally from the chloroplast genome were found within the mitogenome, pointing to the occurrence of horizontal gene transfer between organelles. This assembled mitogenome stands as a valuable resource for subsequent studies on mitogenome structures, their evolution, and molecular biology.

To investigate the effect of sulfated modification on the structure and function of coconut haustorium polysaccharide (CHP), three kinds of sulfated coconut haustorium polysaccharides (SCHP-2, SCHP-3, and SCHP-4) were prepared using sulfation reagents containing different ratios of chlorosulfonic acid and pyridine (v/v, mL/mL: 1/2, 1/3, and 1/4) after extracting CHP from the raw materials of coconut haustorium, and their basic chemical compositions, structural characteristics and antioxidant activity in vitro were compared and analyzed. Results showed that all three sulfation reagents were able to modify CHP (characteristic peaks of S=O and C-O-S were observed near 1100~1250 cm−1 and 820 cm−1 in infrared spectra, respectively), and the degree of substitution (DS) was the highest (0.75) at the ratio of chlorosulfonic acid and pyridine for 1/2. The total sugar, uronic acid content, and molecular weight of the three SCHP decreased, and the molar content of monosaccharides also changed when comparing with that of CHP. The thermal stability had slightly weakened as well (the degradation temperature of polysaccharides decreased from 211.17 ℃ and 282.01 ℃ of CHP to 194.86~207.70 ℃ and 233.35~262.46 ℃ of SCHP, respectively). The results of antioxidant experiments in vitro showed that the scavenging activity of SCHP on DPPH and hydroxyl radicals was lower than that of CHP, and the larger the DS was, the more obvious the decrease in activity was. In terms of the ABTS+ radicals scavenging ability and ferrous ions chelating activity, increasing DS could enhance the activity of SCHP. At 8 mg/mL, the ABTS+ radicals scavenging rate (54.82%) and ferrous ions chelating rate (15.59%) of SCHP-2 were significantly (P

Abstract Defoliation is a primary agronomic traits, its variation depends on different plant species or cultivars. The present article assess the leaf morphological responses, oxidative metabolites and enzymatic activities at sheath base of sugarcane cultivars during defoliation stage of plant leaves. The mature leaf sheath of GT47 strongly wrapped to the stem, and no stem was exposed. The upper and lower edges of the immature fusing abscission zone were parallel, and slightly lower browning area (+ 3 to + 7 leaf position). The ROC22 cultivar was monitored highest leaf sheath-based cellulose and lignin content, followed by GT60 and GT47. Peroxidase activity was higher in leaf sheath base edge (ROC22) as compare to other cultivars. The malondialdehyde content was found highest in GT60, followed by ROC22, and GT47. The exo-β-1,4-glucanase/ cellobiohydrolase activity was found highest in the margin of GT47 than lateral and medial axis of ROC22 and GT60. The axis activity increased exponentially, and ROC22 gradually decreased from the periphery of the mid-axis and lower than GT47 and GT60 in the lateral and mid-axis of leaf. In conclusion, the mature leaves are easy to defoliate mainly loose leaf sheaths, large leaf sheath inclination angles, more deformation during the growth period of the abscission zone, early with large cracks, and slow browning process. Leaf sheaths with high fibre and lignin content showed significant hardness and thickness. The sugarcane cultivars showed positive correlation between peroxidase and malondialdehyde content with the browning process at the base of mature leaf sheaths.

Abstract The study was to evaluate the clinical outcomes of azvudine versus nirmatrelvir-ritonavir against omicron strains of coronavirus disease 2019 infections and determine their comparative effectiveness. This retrospective study included 716 patients who received nirmatrelvir-ritonavir (NR group) or azvudine (FNC group) at Peking Union Medical College Hospital between 1 November 2022 and 27 February 2023. Patients in the FNC group (n = 304) were younger, exhibited less severe symptoms, started antiviral therapy later, received corticosteroids more frequently, and used tocilizumab less frequently than patients in the NR group (n = 412). Within 28 d of therapy, 40 (9.7%) and 20 (6.6%) deaths were in the NR and FNC groups, respectively. No differences were observed between drugs and mortality rates (odds ratio [OR] 0.78, 95% CI 0.40–1.5, P = 0.45), clinical improvement (OR 0.79, 95% CI 0.79–1.3, P = 0.38), and clinical progression (OR 1.0, 95% CI 0.58–1.8, P = 0.96). More patients in the NR group experienced platelet decline than those in the FNC group (17.6% vs. 8.9%, P = 0.034). This study indicated that the effectiveness and safety of azvudine were comparable to those of nirmatrelvir-ritonavir.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a common malignant tumor of the digestive tract. Although gemcitabine and other therapeutic agents are effective in patients with advanced and metastatic pancreatic cancer, drug resistance has severely limited their use. However, the mechanisms of gemcitabine resistance in pancreatic cancer are poorly understood. In this study, ATAC-seq, ChIP-seq, and RNA-seq were performed to compare chromatin accessibility and gene expression in a patient-derived tumor xenograft (PDX) model of pancreatic cancer with or without gemcitabine resistance. Analyzing these sequencing data, we found a dramatic change in chromatin accessibility in the PDX model of gemcitabine-resistant tissues and identified a key gene, UBR7, which plays an important role in mediating gemcitabine resistance. Further research found that depletion of UBR7 significantly increased pancreatic carcinogenesis and the immunosuppressive microenvironment. Mechanistically, depleted UBR7 increased the stability of PRMT5, thereby promoting glycolysis in pancreatic cancer cells. Finally, an inhibitor that blocks PRMT5 (DS-437) significantly reduced gemcitabine resistance in pancreatic cancer caused by UBR7 depletion. In conclusion, our results illustrate that the UBR7-PRMT5 axis is a key metabolic regulator of PDAC and a promising target for the clinical treatment of gemcitabine resistance in PDAC.

Abstract While the elevation of serum uric acid (SUA) is acknowledged as a risk factor for chronic kidney disease, the independent extent to which variations in SUA levels are correlated with temporal changes in estimated glomerular filtration rate (eGFR) remains uncertain. In light of this uncertainty, our research endeavored to elucidate the temporal associations between change in SUA and rapid eGFR decline in China. In this longitudinal study of China’s middle-aged and elderly between 2011 and 2015, we analyzed 5421 individuals with complete SUA and eGFR data. Logistic regression was applied to evaluate the risk factors associated with a rapid eGFR decline (defined by a 5 mL/min/1.73 m2 decrease or falling to less than 15 mL/min/1.73 m2 by 2015), adjusted for age, gender, marital, residence, income, BMI, hypertension, diabetes, dyslipidemia, CRP, Hba1c, baseline eGFR and baseline SUA. Linear regression was used to evaluate the relationship between variations in SUA and changes in eGFR. After multivariable adjustments, the risk factors of a rapid eGFR decline included aging (OR per 1-year increase: 1.1, 95% CI 1.08–1.12, P

Commercial sterility does not guarantee the sustained stability of ultrahigh temperature (UHT) milk over 6 months shelf life. We explore the microbiota presented in normal (SZ) and quality deteriorated UHT milk (QY and WY) products from the same brand. Based on high-throughput sequencing research results, 11 phyla and 54 genera were identified as dominant microbiota. Pseudomonas, Streptococcus, and Acinetobacter as core functional microbiota significantly influenced the UHT milk quality properties. Moreover, principal component analysis (PCA) and multivariate analyses were used to examine the quality characteristics, including 11 physicochemical parameters, 10 fatty acids, and 2 enzyme activities, in normal and quality deteriorated UHT milk. We found that the abundance of Pseudomonas increased in quality deteriorated milk (WY) and showed a significant positive correlation with heat-resistant protease content. Acinetobacter in quality deteriorated milk (QY) also considerably contributed to the content of heat-resistant lipase, which resulted in spoilage deterioration of UHT milk.

Pachylophus belongs to the subfamily Chloropinae, the second most diverse subfamily of Chloropidae. However, there have been few complete mitochondrial genomes of Chloropinae reported in the public database. Consequently, we sequenced and annotated the complete mitochondrial genome of Pachylophus rufescens (de Meijere, 1904). The whole mitochondrial genome is 17, 926 bp in length, consisting of 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs) and two ribosomal RNAs (rRNAs). The mitochondrial genome exhibits high A + T bias, accounting for 79.7% of its entirety. All PCGs start with ATN codon and end with TAN or incomplete stop codon TA or single T. The Maximum likelihood phylogenetic tree revealed a close relationship between Pachylophus and Cetema. This study contributes to the expansion of the mitochondrial genome library of Chloropinae, providing a valuable resource for gaining insights into the evolutionary history of Chloropidae.

Compound hazards caused by tropical cyclones involve interactions among multiple hazards, such as wind, rainfall, and storm surge, significantly increasing the uncertainty and destructiveness of disasters. Existing studies primarily focus on probabilistic analyses of single or dual hazards associated with tropical cyclones, revealing limitations in handling high-dimensional data and complex dependencies. This study developed the ComHazAsTC-RRE (Compound Hazard Assessment of Tropical Cyclones within Repeatable, Reproducible, and Expandable Framework) model to analyze the compound hazards of wind, rainfall, and storm surge induced by tropical cyclones and successfully applied it to China’s coast. We collected globally accessible daily records of maximum wind speed, cumulative rainfall, and maximum storm surge for China’s coastal areas from 1979 to 2018. Using a C-Vine Copula with wind speed as the core, incorporating rainfall and storm surge as branches, we accurately captured complex dependencies of tropical cyclones. Our various return period analyses underscore the importance of considering multiple hazards and their interactions. Additionally, the application of Compound Hazard Index in China reveals that southeastern coastal areas are subjected to significantly higher compound hazards, driven by high wind speeds and strong spatial–temporal consistency of hazards. An in-depth analysis of failure probabilities indicates that neglecting the interactions among hazards can result in substantial additional cost for engineering projects, especially during severe tropical cyclones. This study offers new perspectives and scientific tools for understanding and addressing compound hazards, formulating effective disaster prevention and mitigation strategies, and supporting the sustainable development of coastal regions worldwide.

In December 2022, China classified COVID-19 as a category B infectious disease. This ended 2 years of close epidemiological surveillance of COVID-19. The objective of this questionnaire was to assess the infection status in the COVID-19 pandemic since December in Henan Province, China, and the prevalence of infection in people who were taking ursodeoxycholic acid (UDCA) during this period. We distributed questionnaires to patients attending the gastroenterology clinic at the First Affiliated Hospital of Henan University of Chinese Medicine. The questionnaire lasted for 3 weeks and a total of 660 were collected, of which the number of people taking UDCA was 70. This is the first investigation into the rate of infection among those taking UDCA during the time of the COVID-19 pandemic. Our results showed that the overall infection rate among those taking UDCA was 71.43% (n = 50), with a 10% (n = 7) rate of asymptomatic infections, which was significantly lower than the 85.42% (n = 504) and 6.27% (n = 37) rates among respondents who did not take. The administration of UDCA showed a trend toward reducing the rate of COVID-19 infection, but the difference was not statistically significant when compared to patients with shorter durations of medication use. While less than 30% of participants remained uninfected during the study period, indicating a potential protective effect, it is important to note that complete prevention of SARS-CoV-2 infection by UDCA was not observed.

ObjectiveCapivasertib, a novel pan-AKT inhibitor, shows significant antitumor activity against hormone receptor-positive advanced breast cancer. However, its cost-effectiveness of this treatment remains uncertain. This study aimed to evaluate the cost-effectiveness of capivasertib plus fulvestrant versus fulvestrant alone for advanced breast cancer treatment from the perspectives of healthcare payers in the United States. Meanwhile, a experimental analysis from the perspective of China, incorporating specific assumptions, was also conducted in this study.MethodsA partitioned survival model was constructed to project the progression of breast cancer. Overall survival (OS) and progression-free survival (PFS) data were obtained from the CAPItello-291 trial and extrapolated for long-term survival estimates. Direct medical costs and utility data were gathered. The primary outcome measure was incremental cost-utility ratio (ICUR) to evaluate the cost-effectiveness of treatment regimen. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analyses (PSA) were conducted to assess the robustness of the results.ResultsThe base-case analysis estimated the ICUR for capivasertib plus fulvestrant versus fulvestrant alone to be $709,647 per quality-adjusted life-year (QALY) in the US. OWSA revealed that the results were sensitive to hazard ratio of OS and the cost of capivasertib. PSA demonstrated that capivasertib plus fulvestrant exhibited a 0% probability of cost-effectiveness in the US.ConclusionOur finding suggests that, at its current price, capivasertib plus fulvestrant regimen is unlikely to be a cost-effective option compared to fulvestrant alone for HR-positive advanced breast cancer patients from the perspective of healthcare system in the US. For the experimental analysis based on specific assumptions from Chinese perspective, the therapy regimen was also found to lack cost-effectiveness.

IntroductionMalignant pleural effusion (MPE) is associated with poor quality of life and mortality in patients with tumors. In clinical practice, we observed that patients with malignant pleural effusion (MPE) and concurrent heart disease exhibited a decrease in MPE volumes following treatment with β-receptor blockers for heart disease. Immunosuppressive tumor microenvironment was found to play a substantial role in the progression of MPE, and mainly attributed to tumor-associated macrophages (TAMs). However, whether β-receptor blockers improve MPE through affecting the immune microenvironment especially TAMs and the potential mechanism behind remains unclear.MethodsIn this study, we collected the MPE samples from MPE and heart disease patients treated with propranolol, and performed flow cytometry experiment to evaluate the effect of propranolol on MPE immune microenvironment. Then, the mechanism that how propranolol effectively reprogrammed the immunosuppressive microenvironment of MPE was conducted by the experiments of mass spectrometry, RNA-seq, flow cytometry, immunofluorescence, western blotting, etc. Lastly, to further evaluate the effect of propranolol on MPE therapy in vivo, we developed a mouse model of MPE. We administrated propranolol into MPE-bearing mice to investigate the therapy efficacy and the changes of MPE microenvironment by the experiments of computed tomography (CT) scanning, flow cytometry, etc.ResultsWe observed that propranolol treatment in MPE patients with heart disease decreased TAM frequency and immunosuppression and enhanced anti-tumor immunity. Macrophages in MPE exhibited an immunosuppressive phenotype via the activation of norepinephrine metabolism. Subsequently, we found that lactate was increased in MPE and may contribute to an increase in TAM frequency and inhibition of anti-tumor immunity by macrophages. Additionally, lactate triggered phenylalanine/norepinephrine signaling and further induced macrophage immunosuppression in an ERK-depended way. Lastly, in the MPE mouse model, propranolol inhibited MPE development and reversed the immune microenvironment of MPE.DiscussionHere, we reveal the mechanism by which lactate induces macrophage immunosuppression via activating phenylalanine/norepinephrine signaling. Our findings highlight that blocking norepinephrine signaling by β-receptor blockers is an attractive therapeutic strategy to enhance anti-tumor immunity in the context of MPE

IntroductionPotatoes and tomatoes are important Solanaceae crops that require effective disease monitoring for optimal agricultural production. Traditional disease monitoring methods rely on manual visual inspection, which is inefficient and prone to subjective bias. The application of deep learning in image recognition has led to object detection models such as YOLO (You Only Look Once), which have shown high efficiency in disease identification. However, complex climatic conditions in real agricultural environments challenge model robustness, and current mainstream models struggle with accurate recognition of the same diseases across different plant species.MethodsThis paper proposes the SIS-YOLOv8 model, which enhances adaptability to complex agricultural climates by improving the YOLOv8 network structure. The research introduces three key modules: 1) a Fusion-Inception Conv module to improve feature extraction against complex backgrounds like rain and haze; 2) a C2f-SIS module incorporating Style Randomization to enhance generalization ability for different crop diseases and extract more detailed disease features; and 3) an SPPF-IS module to boost model robustness through feature fusion. To reduce the model’s parameter size, this study employs the Dep Graph pruning method, significantly decreasing parameter volume by 19.9% and computational load while maintaining accuracy.ResultsExperimental results show that the SIS-YOLOv8 model outperforms the original YOLOv8n model in disease detection tasks for potatoes and tomatoes, with improvements of 8.2% in accuracy, 4% in recall rate, 5.9% in mAP50, and 6.3% in mAP50-95.DiscussionThrough these network structure optimizations, the SIS-YOLOv8 model demonstrates enhanced adaptability to complex agricultural environments, offering an effective solution for automatic crop disease detection. By improving model efficiency and robustness, our approach not only advances agricultural disease monitoring but also contributes to the broader adoption of AI-driven solutions for sustainable crop management in diverse climates.

BackgroundMajor Depressive Disorder (MDD) is occurring at a progressively younger age, and suicide is now the second leading cause of death among adolescents with MDD. Studies have shown that structural magnetic resonance imaging (sMRI) can improve the positioning accuracy and anti-depressant effects of repetitive transcranial magnetic stimulation (rTMS), thereby reducing suicidal ideation.ObjectiveTo compare the efficacy of sMRI-guided rTMS combined with pharmacotherapy, surface 5-cm rTMS positioning combined with pharmacotherapy, and pharmacotherapy alone on reducing depressive symptoms and suicidal ideation (SI) in MDD adolescents.MethodsThis was an open-label study of adjustable-dose pharmacotherapy combined with rTMS for the treatment of depressive symptoms and suicidal ideation in MDD adolescents. The three study groups were as follows: sMRI navigation for individualized rTMS coordinates targeting the dorsolateral prefrontal cortex (DLPFC) and in combination with pharmacotherapy for 10 rTMS sessions over two weeks; surface 5-cm positioning for DLPFC in combination with pharmacotherapy for 10 rTMS sessions over two weeks; pharmacotherapy. All patients received only one type of SSRIs anti-depressant. A total of 123 Chinese adolescents aged 13-18 with MDD were enrolled, and psychological parameters were evaluated in the first and second weeks of treatment.ResultsFollowing treatment, the clinical symptoms improved in all three groups. The sMRI navigation group exhibited significantly more improvement in depressive symptoms and suicidal ideation, without severe adverse reactions.ConclusionTen sessions of rTMS treatment are feasible and effective in improving depressive symptoms and reducing SI in MDD adolescents. The combination of sMRI navigation rTMS and pharmacotherapy was found to yield the best outcomes.Clinical trial registrationhttps://www.medicalresearch.org.cn/index, identifier MR-33-24-030536.

Abstract Mitochondrial permeability transition pore (mPTP) opening is a key hallmark of injured type II alveolar epithelial cells (AECIIs) in idiopathic pulmonary fibrosis (IPF). Inhibiting mPTP opening in AECIIs is considered a potential IPF treatment. Herein, a “double braking” strategy on mPTP by cyclosporin A (CsA) derived ionizable lipid with 3D structure (3D‐lipid) binding cyclophilin D (CypD) and siRNA downregulating mitochondrial calcium uniporter (MCU) expression is proposed for treating IPF. 3D‐lipid and MCU targeting siRNA (siMCU) are co‐assembled to form stable 3D‐LNP/siMCU nanoparticles (NPs), along with helper lipids. In vitro results demonstrated that these NPs effectively inhibit mPTP opening by 3D‐lipid binding with CypD and siRNA downregulating MCU expression, thereby decreasing damage‐associated molecular patterns (DAMPs) release and suppressing epithelial‐to‐mesenchymal transition (EMT) process in bleomycin‐induced A549 cells. In vivo results revealed that 3D‐LNP/siMCU NPs effectively ameliorated collagen deposition, pro‐fibrotic factors secretion, and fibroblast activation in bleomycin‐induced pulmonary fibrosis (PF) mouse models. Moreover, compared to the commercial MC3‐based formulation, optimized Opt‐MC3/siRNA NPs with incorporating 3D‐lipid as the fifth component, showed superior therapeutic efficacy against PF due to their enhanced stability and higher gene silencing efficiency. Overall, the nanomedicine containing 3D‐lipid and siMCU will be a promising and potential approach for IPF treatment.

BackgroundAlthough previous studies have reported the dysregulation of respiratory tract microbiota in infectious diseases, insufficient data exist regarding respiratory microbiota imbalances in the lower respiratory tracts of children with pulmonary tuberculosis (PTB). In this study, we assessed the value of mNGS in the pathogen diagnosis and microbiome analysis of PTB patients using bronchoalveolar lavage fluid (BALF) samples.MethodsA total of 64 participants, comprising 43 pediatric PTB and 21 pediatric pneumonia patients were recruited in the present study. BALF samples were collected from the above participants. Parallel comparisons between mNGS and conventional microbial test (CMT) pathogen detection were performed. Moreover, the diversity and structure of all 64 patients’ lung BALF microbiomes were explored using the mNGS data.ResultsComparing to the final clinical diagnosis, mNGS in BALF samples produced a sensitivity of 46.51%, which was lower than that of TB-PCR (55.00%) and Xpert (55.00%). The diagnostic efficacy of PTB can be highly enhanced by mNGS combined with TB-PCR (AUC=0.8140, P

ObjectiveThis study aimed to analyze the characteristics of surgical litigation cases and the risk factors that contribute to catastrophic compensation.MethodsWe downloaded and retrieved all cases related to surgical litigation cases from the China Jufaanli Database between 2008 and 2023. Multivariate logistic regression analysis was employed to identify independent risk factors that may contribute to catastrophic compensation.ResultsThis study included a total of 8,331 successfully resolved surgical litigation cases. Of these, 5,114 hospitals were defendants, with 25.34% of them involved in two or more lawsuits, thereby categorized as “repeat defendants.” The total compensation amount was $269,163,545, with the highest compensation reaching $540,008. Most surgical litigation cases were concentrated in the eastern regions of China, with tertiary hospitals being the most frequently involved. The most common type of injury outcome was patient death. Compensation amounts and high compensation rates for severe disability exceeded those for death (p

Abstract As unique building blocks for advancing optoelectronics, 2D semiconducting transition metal dichalcogenides have garnered significant attention. However, most previously reported MoS2 photodetectors respond only to visible light with limited absorption, resulting in a narrow spectral response and low sensitivity. Here, a surrounding homojunction MoS2 photodetector featuring localized p‐type nitrogen plasma doping on the surface of n‐type MoS2 while preserving a high‐mobility underlying channel for rapid carrier transport is engineered. The establishment of p‐n homojunction facilitates the efficient separation of photogenerated carriers, thereby boosting the device's intrinsic detection performance. The resulting photoresponsivity is 6.94 × 104 A W−1 and specific detectivity is 1.21 × 1014 Jones @ 638 nm, with an optimal light on/off ratio of ≈107 at VGS = −27 V. Notably, the introduction of additional bands within MoS2 bandgap through nitrogen doping leads to an extrinsic broadband response to short‐wave infrared. The device exhibits a photoresponsivity of 34 A W−1 and a specific detectivity of up to 5.92 × 1010 Jones @ 1550 nm. Furthermore, the high‐performance broadband response is further demonstrated through imaging and integration with waveguides, paving the way for next generation of multifunctional imaging systems and high‐performance photonic chips.

Abstract Objective To provide evidence for choosing surgical or nonsurgical treatment for epilepsy in patients with unilateral multilobar and hemispheric polymicrogyria (PMG). Methods We searched published studies until September 2022 related to unilateral multilobar and hemispheric PMG and included patients who were followed up at the Pediatric Epilepsy Centre of Peking University First Hospital in the past 10 years. We summarized the clinical characteristics and compared the long‐term outcomes after surgical or nonsurgical (anti‐seizure medications, ASMs) treatment. Results A total of 70 patients (49 surgical, 21 non‐surgical) with unilateral multilobar and hemispheric PMG were included. The median age at epilepsy onset was 2.5 years (1.0–4.1). The most common seizure types were focal and atypical absence seizures. In the whole cohort, 87.3% had hemiparesis and 67.1% had electrical status epilepticus during slow sleep (ESES). There were significant differences in age at epilepsy onset, extent of lesion, and EEG interictal discharges between the two groups. At the last follow‐up (median 14.1 years), the rates of seizure‐freedom (81.6% vs. 57.1%, p = 0.032) and ASM discontinuation (44.4% vs. 6.3%, p = 0.006) were higher in the surgical group than in the nonsurgical group. Patients in the surgical group had a higher rate of seizure‐freedom with complete resection/disconnection than with subtotal resection (87.5% vs. 55.6%, p = 0.078), but with no statistically significant difference. In the nonsurgical group, more extensive lesions were associated with worse seizure outcomes. Cognition improved postoperatively in 90% of surgical patients. Significance In patients with unilateral multilobar and hemispheric PMG, the age of seizure onset, the extent of the lesion and EEG features can help determine whether surgery should be performed early. Additionally, surgery could be more favorable for achieving seizure freedom and cognitive improvement sooner. Plain Language Summary We aim to summarize clinical characteristics and compare the long‐term outcomes after surgical and nonsurgical (ASM) treatment to provide a basis for treatment decisions for patients with unilateral multilobar and hemispheric polymicrogyria (PMG)‐related epilepsy. We found that patients with unilateral hemispheric and multilobar PMG had significantly higher rates of seizure freedom and ASM discontinuation with surgical treatment than with nonsurgical treatment. In the surgical group, seizure outcomes were better in patients treated with complete resection/disconnection than in those treated with subtotal resection, but the difference was not statistically significant.

Abstract Background Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. Methods The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB −/− mice were generated, and relevant in vivo experiments were performed. Results Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB −/− mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. Conclusion Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.

Abstract Background Understanding the mechanism of male sterility is crucial for producing hybrid seeds and developing sterile germplasm resources. However, only a few cytoplasmic male sterility (CMS) lines of cotton have been produced due to several challenges, like inadequate variation of agronomic traits, incomplete sterility, weak resilience of restorer lines, and difficulty in combining strong dominance. Therefore, the morphological and cytological identification of CMS in cotton will facilitate hybrid breeding. Results Two F2 segregating populations of cotton were constructed from cytoplasmic male sterile lines (HaA and 01A, maternal) and restorer lines (HaR and 26R, paternal). Genetic analysis of these populations revealed a segregation ratio of 3:1 for fertile to sterile plants. Phenotypic analysis indicated no significant differences in traits of flower bud development between sterile and fertile plants. However, sterile plants exhibited smaller floral organs, shortened filament lengths, and anther atrophy on the flowering day in comparison with the fertile plants. When performed scanning electron microscopy (SEM), the two F2 populations revealed morphological variations in the anther epidermis. Cellular analysis showed no significant differences in pollen development before pollen maturation. Interestingly, between the pollen maturation and flowering stages, the tapetum layer of sterile plants degenerated prematurely, resulting in abnormal pollen grains and gradual pollen degradation. Conclusion The results of this study suggest that fertility-restoring genes are controlled by a single dominant gene. Sterile plants exhibit distinctive floral morphology, which is characterized by stamen atrophy and abnormal anthers. Pollen abortion occurs between pollen maturity and flowering, indicating that premature tapetum degradation may be the primary cause of pollen abortion. Overall, our study provides a theoretical basis for utilizing CMS in hybrid breeding and in-depth investigation of the dominant configuration of cotton hybrid combinations, mechanisms of sterility, and the role of sterile and restorer genes.

Abstract Background Hemorrhagic stroke is a devastating cerebrovascular event with a high rate of early mortality and long-term disability. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) for neurological conditions, such as intracerebral hemorrhage (ICH), has garnered considerable interest, has garnered considerable interest, though their mechanisms of action remain poorly understood. Methods EVs were isolated from human umbilical cord MSCs, and SPECT/CT was used to track the 99mTc-labeled EVs in a mouse model of ICH. A series of comprehensive evaluations, including magnetic resonance imaging (MRI), histological study, RNA sequencing (RNA-Seq), or miRNA microarray, were performed to investigate the therapeutic action and mechanisms of MSC-EVs in both cellular and animal models of ICH. Results Our findings show that intravenous injection of MSC-EVs exhibits a marked affinity for the ICH-affected brain regions and cortical neurons. EV infusion alleviates the pathological changes observed in MRI due to ICH and reduces damage to ipsilateral cortical neurons. RNA-Seq analysis reveals that EV treatment modulates key pathways involved in the neuronal system and metal ion transport in mice subjected to ICH. These data were supported by the attenuation of neuronal ferroptosis in neurons treated with Hemin and in ICH mice following EV therapy. Additionally, miRNA microarray analysis depicted the EV-miRNAs targeting genes associated with ferroptosis, and miR-214-3p was identified as a regulator of neuronal ferroptosis in the ICH cellular model. Conclusions MSC-EVs offer neuroprotective effects against ICH-induced neuronal damage by modulating ferroptosis highlighting their therapeutic potential for combating neuronal ferroptosis in brain disorders.

Abstract Korla pear has a unique taste and aroma and is a breeding parent of numerous pear varieties. It is susceptible to Valsa mali var. pyri, which invades bark wounded by freezing injury. Its genetic relationships have not been fully defined and could offer insight into the mechanism for freezing tolerance and disease resistance. We generated a high-quality, chromosome-level genome assembly for Korla pear via the Illumina and PacBio circular consensus sequencing (CCS) platforms and high-throughput chromosome conformation capture (Hi-C). The Korla pear genome is ~ 496.63 Mb, and 99.18% of it is assembled to 17 chromosomes. Collinearity and phylogenetic analyses indicated that Korla might be derived from Pyrus pyrifolia and that it diverged ~ 3.9-4.6 Mya. During domestication, seven late embryogenesis abundant (LEA), two dehydrin (DHN), and 54 disease resistance genes were lost from Korla pear compared with P. betulifolia. Moreover, 21 LEA and 31 disease resistance genes were common to the Korla pear and P. betulifolia genomes but were upregulated under overwintering only in P. betulifolia because key cis elements were missing in Korla pear. Gene deletion and downregulation during domestication reduced freezing tolerance and disease resistance in Korla pear. These results could facilitate the breeding of novel pear varieties with high biotic and abiotic stress resistance.

Abstract Background Social support is widely recognized as a protective factor against psychological distress, especially for the elderly with chronic diseases. Therefore, effective tools for measuring social support are of great significance for both research and clinical practice. This study aims to cross-culturally adapt the German Social Support Scale (F-SozU) into Chinese and assess its psychometric properties among older adults with chronic diseases. Methods A cross-sectional study was conducted in a Chinese tertiary hospital. Four hundred ninety-six older adults that were approached via a convenience sampling method completed the Chinese version of the F-SozU. Content validity was evaluated using the two-round Delphi method. Psychometric properties, including item analysis, content validity, structure validity, convergent and discriminant validity and reliability were examined. Result The final version of C-F-SozU is a three-factor structure consisting of 23 items. All indicators of item analysis are acceptable. Adequate content validity was ensured by the expert panel (I-CVI = 0.80–1.00, S-CVI = 0.965) and participants. The confirmatory factor analysis model revealed that the factor structure of the C-F-SozU fitted the original scale (χ 2 /df = 2.088, CFI = 0.998, GFI = 0.943, TLI = 0.997, IFI = 0.998, RMSEA = 0.064 and SRMR = 0.043). The total Cronbach’s α was 0.956, and the test–retest reliability coefficient was 0.887. The convergent validity (average variance extracted = 0.517–0.995) and discriminant validity were found to be satisfactory. No floor/ceiling effect was found. Conclusion The 23-item C-F-SozU demonstrates robust reliability and validity, rendering it a valuable instrument for evaluating social support among older adults with chronic diseases in China. The three-factor structure of the scale allows for a more detailed assessment of the social support, with the scores of each dimension and the total score being of significant reference value. More comprehensive studies may be required to confirm its effectiveness and applicability.

Abstract Excessive phosphorus (P) levels can disrupt nutrient balance in plants, adversely affecting growth. The molecular responses of Pennisetum species to high phosphorus stress remain poorly understood. This study examined two Pennisetum species, Pennisetum americanum × Pennisetum purpureum and Pennisetum americanum, under varying P concentrations (200, 600 and 1000 µmol·L− 1 KH2PO4) to elucidate transcriptomic alterations under high-P conditions. Our findings revealed that P. americanum exhibited stronger adaption to high-P stress compared to P. americanum× P. purpureum. Both species showed an increase in plant height and leaf P content under elevated P levels, with P. americanum demonstrating greater height and higher P content than P. americanum× P. purpureum. Transcriptomic analysis identified significant up- and down-regulation of key genes (e.g. SAUR, GH3, AHP, PIF4, PYL, GST, GPX, GSR, CAT, SOD1, CHS, ANR, P5CS and PsbO) involved in plant hormone signal transduction, glutathione metabolism, peroxisomes, flavonoid biosynthesis, amino acid biosynthesis and photosynthesis pathways. Compared with P. americanum× P. purpureum, P. americanum has more key genes in the KEGG pathway, and some genes have higher expression levels. These results contribute valuable insights into the molecular mechanisms governing high-P stress in Pennisetum species and offer implications for broader plant stress research.

Objective: To investigate whether melatonin (MT) secretion in different parts of the gastrointestinal tract (GIT) exhibits seasonal variations and its correlation with immune regulation. Methods: Sixty Sprague-Dawley rats were divided into control and model groups, and the pineal gland was removed in the model group. Stomach, jejunum, ileum, and colon tissues were obtained during the spring equinox, summer solstice, beginning of autumn, autumn equinox, and winter solstice. The levels of MT, MT receptors (MR), arylalkylamine N-acetyltransferase (AANAT), hydroxyindole-O-methyltransferase (HIOMT), interleukin-2 (IL-2), and interleukin-10 (IL-10) in the GIT were measured using enzyme-linked immunosorbent assay. Results: Except for the stomach, the jejunum, ileum, and the colon showed seasonal tendencies in MT secretion. In the control group, MT secretion in the jejunum and ileum was the highest in the long summer, and colonic MT secretion was the highest in winter. In the model group, MT levels in the colon were highest in the summer. The seasonal rhythms of the MR, AANAT, HIOMT, IL-2, and IL-10 in the colon were roughly similar to those of MT, and changed accordingly after pinealectomy. Conclusions: Gastrointestinal MT secretion is related to seasonal changes, and MT secretion in each intestinal segment is influenced by different seasons. The biological effects of MT in the gut are inextricably linked to the mediation of MR, and a hormone-receptor linkage exists between MT and MR. The effect of seasonal changes on the gastrointestinal immune system may be mediated through the regulation of seasonal secretion of MT.

Abstract Tumor-draining lymph nodes (TDLNs) are usually the first station of tumor metastasis in lung cancer. TDLNs+ have distinct pathomorphologic and tumor microenvironment (TME)-compositional patterns, which still need to be thoroughly investigated in lung adenocarcinoma (LUAD). Here, we enrolled 312 LUAD patients with TDLNs+ from our institution between 2015 and 2019. 3DHISTECH was used to scan all of the TDLNs+. Based on morphologic features, TDLNs+ patterns were classified as polarized-type or scattered-type, and TME-compositional patterns were classified as colloid-type, necrosis-type, specific-type, and common-type. Multivariate analysis revealed an increased risk of early recurrence associated with scattered-type (HR 2.37, 95% CI: 1.06–5.28), colloid-type (HR 1.95, 95% CI: 1.03–3.67), and necrosis-type (HR 2.21, 95% CI: 1.13–4.89). NanoString transcriptional analysis revealed an immunosuppression and vascular invasion hallmark in scattered and necrosis patterns and an immunoactivated hallmark in polarized and common patterns. According to imaging mass cytometry (IMC), the scattered and necrosis patterns revealed that germinal centers (GC) were compromised, GCB cell and T cell proliferation were deficient, tumor cells had the potential for proliferation, and the immune attack may be weaker. In this study, we present evidence that LUAD patients have distinct patterns and immune hallmarks of TDLNs+ related to their prognosis.

Abstract Respiratory failure, intracranial hemorrhage and infection were more common in hyperleukocytic acute myeloid leukemia patients than in non-hyperleukocytic leukemia patients. Compared with non-apheresis treatment, the white blood cells decreased significantly and the infection rate decreased after apheresis treatment. However, the treatment time of leukapheresis in patients with hyperleukocytic leukemia is very long, while it is more damaging to cells. In this study, which conducted a retrospective analysis on patients with hyperleukocytic acute myeloid leukemia, the process of centrifugation of normal cells and patients’ cells by apheresis machine was simulated in vitro. Through selecting 5 healthy persons and 11 patients with hyperleukocytic acute myeloid leukemia, extracting their blood samples and performing in vitro centrifugation at different speeds or duration, we observed the changes of the numbers and morphology of peripheral blood cells in healthy people and patients, so as to explore the optimal centrifugation parameters during leukapheresis. The cells obtained by the optimal centrifugation parameters were cryopreserved and two groups of mice (10 mice in each group) were used to establish leukemia animal models. Through the research, it is found that when the centrifugal speed is below 6000 rpm, the damage to blood cells in healthy people and in patients with hyperleukocytic leukemia is not obvious. When the centrifugal speed is above 6000 rpm, the platelets will be damaged significantly. The cells obtained under the optimal centrifugation parameters can be successfully cryopreserved and used to establish leukemia animal models. This study is of great significance for improving the efficiency and reducing the side effects of leukapheresis, and is helpful to improve the treatment of white blood cells reduction.

Abstract Background There is growing evidence of bidirectional associations between rheumatoid arthritis and adverse pregnancy outcomes (APOs) in observational studies, but little is known about the causal direction of these associations. Therefore, we explored the potential causal relationships between rheumatoid arthritis and APOs using a bidirectional two-sample Mendelian randomization (MR) in European and Asian populations. Methods We conducted a bidirectional two-sample Mendelian randomization analysis using available summary statistics from released genome-wide association studies. Summary statistics for instrument–outcome associations were retrieved from two separate databases for rheumatoid arthritis and adverse pregnancy outcomes, respectively. The inverse-variance weighted method was used as the primary MR analysis, and cML-MA-BIC was used as the supplementary analysis. MR-Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran Q statistic method were implemented as sensitivity analyses approach to ensure the robustness of the results. Results Our study showed that a higher risk of rheumatoid arthritis in the European population was associated with gestational hypertension (OR: 1.04, 95%CI: 1.02–1.06), pre-eclampsia (OR: 1.06, 95%CI: 1.01–1.11), fetal growth restriction (OR: 1.08, 95%CI: 1.04–1.12), preterm delivery (OR:1.04, 95%CI: 1.01–1.07). Furthermore, we found no evidence that APOs had causal effects on rheumatoid arthritis in the reverse MR analysis. No association between rheumatoid arthritis and APOs was found in East Asian population. There was no heterogeneity or horizontal pleiotropy. Conclusions This MR analysis provides the positive causal association from rheumatoid arthritis to gestational hypertension, pre-eclampsia, fetal growth restriction and preterm delivery genetically. It highlights the importance of more intensive prenatal care and early intervention among pregnant women with rheumatoid arthritis to prevent potential adverse obstetric outcomes.

Abstract Background Mesenchymal stem cells (MSCs) demonstrate a wide range of therapeutic capabilities in the treatment of inflammatory bowel disease (IBD). The intraperitoneal injection of MSCs has exhibited superior therapeutic efficacy on IBD than intravenous injection. Nevertheless, the precise in vivo distribution of MSCs and their biological consequences following intraperitoneal injection remain inadequately understood. Additional studies are required to explore the correlation between MSCs distribution and their biological effects. Methods First, the distribution of human umbilical cord MSCs (hUC-MSCs) and the numbers of Treg and Th17 cells in mesenteric lymph nodes (MLNs) were analyzed after intraperitoneal injection of hUC-MSCs. Subsequently, the investigation focused on the levels of transforming growth factor beta1 (TGF-β1), a key cytokine to the biology of both Treg and Th17 cells, in tissues of mice with colitis, particularly in MLNs. The study also delved into the impact of hUC-MSCs therapy on Treg cell counts in MLNs, as well as the consequence of TGFB1 knockdown hUC-MSCs on the differentiation of Treg cells and the treatment of IBD. Results The therapeutic effectiveness of intraperitoneally administered hUC-MSCs in the treatment of colitis was found to be significant, which was closely related to their quick migration to MLNs and secretion of TGF-β1. The abundance of hUC-MSCs in MLNs of colitis mice is much higher than that in other organs even the inflamed sites of colon. Intraperitoneal injection of hUC-MSCs led to a significant increase in the number of Treg cells and a decrease in Th17 cells especially in MLNs. Furthermore, the concentration of TGF-β1, the key cytokine for Treg differentiation, were also found to be significantly elevated in MLNs after hUC-MSCs treatment. Knockdown of TGFB1 in hUC-MSCs resulted in a noticeable reduction of Treg cells in MLNs and the eventually failure of hUC-MSCs therapy in colitis. Conclusions MLNs may be a critical site for the regulatory effect of hUC-MSCs on Treg/Th17 cells and the therapeutic effect on colitis. TGF-β1 derived from hUC-MSCs promotes local Treg differentiation in MLNs. This study will provide new ideas for the development of MSC-based therapeutic strategies in IBD patients.

Abstract Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT (Cas12a-based One-for-all High-speed Isothermal Test), a one-pot CRISPR-based assay for indel detection. Leveraging an engineered AsCas12a protein variant with high mismatch tolerance and broad PAM scope, CoHIT can use a single crRNA to detect multiple NPM1 gene c.863_864 4-bp insertions in acute myeloid leukemia (AML). After optimizing multiple parameters, CoHIT achieves a detection limit of 0.01% and rapid results within 30 minutes, without wild-type cross-reactivity. It successfully identifies NPM1 mutations in 30 out of 108 AML patients and demonstrates potential in monitoring minimal residual disease (MRD) through continuous sample analysis from three patients. The CoHIT method is also competent for detecting indels of KIT, BRAF, and EGFR genes. Integration with lateral flow test strips and microfluidic chips highlights CoHIT’s adaptability and multiplexing capability, promising significant advancements in clinical cancer diagnostics.

Abstract Objective To identify differentially expressed long noncoding RNAs (lncRNAs) in condyloma acuminatum (CA) and to explore their probable regulatory mechanisms by establishing coexpression networks. Methods High-throughput RNA sequencing was performed to assess genome-wide lncRNA expression in CA and paired adjacent mucosal tissue. The expression of candidate lncRNAs and their target genes in larger CA specimens was validated using real-time quantitative reverse transcriptase polymerase chain reaction (RT‒qPCR). Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for the functional enrichment analysis of these candidate lncRNAs and differential mRNAs. The coexpressed mRNAs of the candidate lncRNAs, calculated by Pearson’s correlation coefficient, were also analysed using GO and KEGG analysis. In addition, the interactions among differentially expressed lncRNAs (DElncRNAs)-cis-regulatory transcription factors (cisTFs)-differentially expressed genes (DEGs) were analysed and their network was constructed. Results A total of 546 lncRNAs and 2553 mRNAs were found to be differentially expressed in CA compared to the paired control. Functional enrichment analysis revealed that the DEGs coexpressed with DElncRNAs were enriched in the terms of cell adhesion and keratinocyte differentiation, and the pathways of ECM-receptor interaction, local adhesion, PI3K/AKT and TGF-ß signaling. We further constructed the network among DElncRNAs-cisTFs-DEGs and found that these 95 DEGs were mainly enriched in GO terms of epithelial development, regulation of transcription or gene expression. Furthermore, the expression of 3 pairs of DElncRNAs and cisTFs, EVX1-AS and HOXA13, HOXA11-AS and EVX1, and DLX6-AS and DLX5, was validated with a larger number of specimens using RT‒qPCR. Conclusion CA has a specific lncRNA profile, and the differentially expressed lncRNAs play regulatory roles in mRNA expression through cis-acting TFs, which provides insight into their regulatory networks. It will be useful to understand the pathogenesis of CA to provide new directions for the prevention, clinical treatment and efficacy evaluation of CA.

ABSTRACT Background Hyperleukocytic acute myeloid leukemia (HL‐AML) is associated with early complications and high mortality rates, highlighting the urgent need for more effective therapeutic strategies. Methods This study conducted label‐free proteomic analysis on serum from HL‐AML and non‐HL AML (NHL‐AML) patients, integrating the data with the OHSU transcriptomic database. Flow cytometry was used to evaluate the in vitro impact of bortezomib. The in vivo effectiveness of bortezomib was assessed using the patient‐derived xenograft (PDX) model of HL‐AML. Results Through integrated analysis of serum proteomics and transcriptomics, we observed an abnormal enrichment of the NF‐kappa B pathway in HL‐AML, suggesting its potential as a novel therapeutic target. Given that bortezomib is an inhibitor of the NF‐kappa B pathway, HL‐AML bone marrow cells were treated with varying concentrations of bortezomib (0, 5, 10, and 20 nM) in vitro. The results indicated a significant cytotoxic effect of bortezomib on HL‐AML cells, accompanied by increased apoptosis rates and decreased proliferation. Co‐administration of bortezomib with the frontline clinical chemotherapeutic regimen of daunorubicin and cytarabine (DA regimen) significantly extended mouse survival. Bone marrow immunophenotyping showed reductions in CD45+ and CD33+ cell populations, indicating disease amelioration. Immunohistochemical analysis further confirmed the inhibitory effect on the NF‐kappa B pathway, as evidenced by reduced levels of P‐IKBα and P‐p65 proteins, validating the proposed therapeutic mechanism. Conclusions These data suggest that combination therapy involving bortezomib and the DA regimen may represent a promising strategy for HL‐AML.

Ozone formation is closely tied to emissions of precursors, meteorological conditions, and atmospheric chemistry. In June 2024, Xuzhou City, located at the intersection of Jiangsu, Shandong, Henan, and Anhui provinces in East China, experienced a series of ozone pollution events. The continuous pollution episodes were characterized by consistently high levels of ozone, with daytime peaks reaching 130 ppb. By combining observations of atmospheric oxidation and the use of the Observation-Based Model model, it was determined that the pollution was the result of a “heatwave-ozone” co-occurring extreme event triggered by elevated temperatures, low humidity, and intense radiation. The heatwave led to increased emissions of VOCs from both natural and human-related sources, with more pronounced contribution from Bio-alkenes and OVOCs. This, in turn, resulted in higher levels of oxidizing agents and ozone formation potential, exacerbating the co-occurrence of heatwaves and ozone extremes. Sensitivity tests on enhanced controls showed that reducing NOx had a significant adverse effect on ozone levels, whereas reducing VOCs had positive benefits, particularly for controlling alkenes. Despite ongoing reductions in anthropogenic VOCs, the elevated temperatures led to an increase in natural VOCs emissions. On average, a 1°C temperature decrease could reduce the reactivity ratio of VOCs to NOx (VOCR/NOxR) by 0.12, thereby enhancing the advantages of emission reductions. Therefore, implementing measures to alleviate extreme heatwaves, such as limiting high-energy consumption and inducing artificial rainfall, can simultaneously reduce the intensity and reactivity of VOC emissions, aiding in the effective implementation of ozone pollution control policies.

Esophageal cancer (EC) is a malignancy with a high incidence and poor prognosis, significantly influenced by dysbiosis in the esophageal, oral, and gut microbiota. This review provides an overview of the roles of microbiota dysbiosis in EC pathogenesis, emphasizing their impact on tumor progression, drug efficacy, biomarker discovery, and therapeutic interventions. Lifestyle factors like smoking, alcohol consumption, and betel nut use are major contributors to dysbiosis and EC development. Recent studies utilizing advanced sequencing have revealed complex interactions between microbiota dysbiosis and EC, with oral pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum promoting inflammation and suppressing immune responses, thereby driving carcinogenesis. Altered esophageal microbiota, characterized by reduced beneficial bacteria and increased pathogenic species, further exacerbate local inflammation and tumor growth. Gut microbiota dysbiosis also affects systemic immunity, influencing chemotherapy and immunotherapy efficacy, with certain bacteria enhancing or inhibiting treatment responses. Microbiota composition shows potential as a non-invasive biomarker for early detection, prognosis, and personalized therapy. Novel therapeutic strategies targeting the microbiota—such as probiotics, dietary modifications, and fecal microbiota transplantation—offer promising avenues to restore balance and improve treatment efficacy, potentially enhancing patient outcomes. Integrating microbiome-focused strategies into current therapeutic frameworks could improve EC management, reduce adverse effects, and enhance patient survival. These findings highlight the need for further research into microbiota-tumor interactions and microbial interventions to transform EC treatment and prevention, particularly in cases of late-stage diagnosis and poor treatment response.

IntroductionThe advent of bevacizumab has considerably transformed the therapeutic landscape for non-small cell lung cancer (NSCLC) patients devoid of specific genetic mutations. A pivotal milestone has been reached with the recent approval of a bevacizumab biosimilar, following rigorous phase III clinical investigations, poised to augment NSCLC therapeutic strategies.MethodsThis retrospective analysis encompasses a large-scale study conducted between January 2021 and December 2023, involving 1058 NSCLC patients (metastatic or locally advanced stages). The research design entailed a comparative assessment of the safety and efficacy profiles of combined therapies using the original bevacizumab and its biosimilar, adhering to RECIST v1.1 criteria. Adverse event grading was standardized using the National Cancer Institute’s CTCAE v5.0.ResultsNotably, the biosimilar demonstrated an objective response rate (ORR) of 29.79% in 606 patients, closely paralleling the 27.41% ORR observed in 452 patients receiving the original drug, with insignificant risk differences (-0.03) and a risk ratio of 0.987, affirming equivalence. Progression-free survival (PFS) was influenced by radiation status, treatment lines, and regimen combinations, while dosage intensity and genetic factors had negligible impacts. The incidence of treatment-emergent adverse events (TEAEs) was slightly higher in the biosimilar group (75.11%) versus the original drug group (72.78%), with grade 3 or more severe TEAEs occurring in 23.6% and 18.5% of patients, respectively (Detailed criteria for the definition and assessment of TEAEs have been added to the Methods section, including the use of the National Cancer Institute’s CTCAE v5.0 for grading).ConclusionsThe study affirms that bevacizumab biosimilars offer equivalent therapeutic efficacy and a similar safety profile to the originator product in the management of locally advanced or metastatic NSCLC. The tolerability of the toxicity profile, coupled with the absence of unforeseen adverse reactions, underscores the viability of biosimilar bevacizumab as a valuable addition to NSCLC treatment regimens. These findings also imply potential benefits for a broader patient population beyond clinical trial confines through the adoption of biosimilar beta-adrenergic blocking agents.

Abstract Sanghuangporus vaninii is a traditional edible and medicinal fungi with a long history in China. Recent studies have focused on its potential in treating diabetes, although the underlying mechanism remains unclear. This study aimed to investigate the antidiabetic and hypolipidemic effects of the formula of S. vaninii compounds (SVC) in diabetic mice and explore the potential improvement in the intestinal microbiota. Oral administration of SVC significantly reduced fasting blood glucose and improved insulin sensitivity and lipid indexes. In addition to its direct effects on glucose levels and insulin sensitivity, SVC was found to have an impact on the intestinal microbiota. The levels of short‐chain fatty acids receiving SVC intervention increased, and 16S rRNA sequencing revealed changes in the abundances of certain bacteria, such as Harryflintia, Helicobacter, Candidatus_Soleaferrea, Klebsiella, and Candidatus_Stoquefichus. These bacteria were found to be negatively associated with glucose and lipid indexes and positively related to body weight and insulin sensitivity. Overall, this study highlights the potential of SVC in treating diabetes and provides a novel perspective for understanding its antidiabetic mechanism through modulation of the intestinal microbiota.