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Abstract Background To introduce the serum total kappa/lambda ratio (K/L) in humoral immunity testing reports to improve the detection rate of M-proteinemia. Methods 156 M protein-positive and 5464 M protein-negative samples confirmed by serum immunofixation electrophoresis(sIFE) were accumulated from January 2021 to December 2023 in the First Affiliated Hospital of Soochow University and the contents of immunoglobulins (IgG, IgA, IgM, kappa and lambda) were tested by Beckman IMMAGE800. All the samples were divided into two groups by time: the modeling group and the validation group. The K/L values in the modeling group were analyzed by SPSS 27.0 to get the receiver operating characteristic curve (ROC). Furthermore, a more in-depth analysis was conducted to verify the reliability of the optimal cutoff values in the validation group. In addition, the levels of immunoglobulins of another group including 106 patients with definite diagnosis of monoclonal gammopathy ranging from January 2021 to June 2024 were traced back to improve the diagnostic efficiency. Results The optimal cutoff values of K/L were 2.31 and 1.43 corresponding to K-type and L-type M-proteinemia respectively by ROC analysis. The sensitivity and specificity were validated as 76.14% and 77.42%. False positives were mainly found in samples with systemic sclerosis (36.84%), hypohepatia (28.71%) and sicca syndrome (27.27%). While false negatives were mainly found in IgA monoclonal gammopathy (38.39%) and IgM monoclonal gammopathy (28.57%). Combining with the detection rules of IgG, IgA and IgM, the sensitivities for the diagnosis of immunoglobulin light chain amyloidosis(AL) and monoclonal gammopathy of undetermined significance(MGUS) can be increased to 83.33% and 85%. Conclusions K/L > 2.31 and K/L

Abstract Background Nephrotic syndrome (NPHS), characterized by proteinuria, hypoalbuminemia, and edema, can be caused by genetic variations. TBC1D8B was recently discovered as a novel disease-causing gene for X-linked NPHS. With only a few reported cases, the clinical manifestations associated with variants of this gene need to be further examined. Methods We recruited a newborn with NPHS complicated by acute kidney injury (AKI) and his parents and tested the potential genetic cause of the disease through trio-whole exome sequencing and Sanger sequencing. Western blotting (WB) was performed using a mutant plasmid to evaluate mutant protein expression levels. Since the TBC1D8B protein interacts with RAB proteins to catalyze the GTPase hydrolysis process, immunofluorescence (IF) can be used to verify the interaction between the TBC1D8B mutant protein and RAB11A/RAB11B, and thus to confirm its effect on the endocytosis and vesicle recycling functions of RAB proteins within the cell. Results The child, at 1 month, showed severe edema and proteinuria and unexplained coma with epilepsy. Ultrasound examination revealed multiple organ enlargement, and MRI showed nonspecific high diffusion-weighted imaging signal characteristics in the splenium of the corpus callosum. Hematoxylin and eosin staining showed diffuse inflammatory cell infiltration in the renal interstitium and multifocal renal tubule lumen expansion. Diffuse fusion of podocyte foot processes was observed under electron microscopy, indicating glomerular podocyte lesions. Genetic testing revealed a maternally inherited novel hemizygous variant, NM_017752: c.628 A > T, p.Lys210Ter, in TBC1D8B. In vitro functional experiments showed that this variant may lead to TBC1D8B protein degradation. IF results showed disrupted interaction with RAB11A/RAB11B, that then affects the biological function of RAB proteins in the process of cell intimal vesicle formation and intracellular transport. Conclusion This study will enrich the mutational and phenotypic spectra of TBC1D8B and demonstrate the potential of this gene variants to cause early-onset NPHS leading to severe kidney disease.

Abstract Background To analyze the clinical manifestations, diagnostic and therapeutic processes of perinatal tuberculosis in children, providing reference for clinicians in the diagnosis and treatment of this disease. Methods A retrospective analysis was conducted on the epidemiological history, clinical manifestations, laboratory and imaging findings, and treatment follow-up of 20 cases of perinatal tuberculosis diagnosed in the Second Department of Infectious Disease, Kunming Children’s Hospital, from February 2014 to September 2021. Results Of the 20 cases, 13 were male (65.0%) and 7 were female (35.0%). The average age at onset was 35.35 ± 23.03days, with an average time from onset to diagnosis of 24.75 ± 15.55days. Tuberculin skin test (TST) was positive in 1 out of 4 cases (25.0%). Gamma interferon release assays (IGRAs) were positive in 9 out of 17 cases (52.9%).acid-fast staining was positive in 7 out of 16 cases (43.7%), and Mycobacterium tuberculosis nucleic acid polymerase-chain-reaction(PCR) was positive in 14 out of 20 cases (70.0%). Chest CT showed miliary changes in 4 out of 19 cases (21.0%), multiple nodular and patchy opacities in 6 out of 19 cases (31.6%), and pulmonary consolidation and atelectasis in 10 out of 19 cases (52.6%). After anti-tuberculosis treatment, 16 out of 20 cases (80.0%) improved, and no recurrence of tuberculosis was observed during follow-up periods ranging from 9 months to 3 years. The growth and development of these children were similar to those of healthy children. Conclusion The clinical manifestations and chest imaging features of perinatal tuberculosis are nonspecific. In suspected cases, it is crucial to investigate the mother’s condition thoroughly and complete etiological examinations to achieve early diagnosis and timely treatment, which can improve prognosis.

Abstract Background Compassion fatigue is common among nurses and can lead to decreased motivation, impaired physical and mental health, and turnover. Nursing interns often face environments the same as professional nurses, yet their compassion fatigue has received less attention. Therefore, this study aims to assess the prevalence and related factors of compassion fatigue among nursing interns. Methods This was a cross-sectional study involving 221 nursing interns in 2 tertiary-level hospitals in Shanghai, China. A general information questionnaire was formulated to investigate the demographic characteristics and internship-related factors of nursing interns. Compassion fatigue was assessed using the Professional Quality of Life Scale [compassion satisfaction (CS), burnout (BO), and secondary traumatic stress (STS)]. Psychological resilience, empathy, and perceived stress were evaluated by the Connor-Davidson Resilience Scale, Jefferson Scales of Empathy, and Perceived Stress Scale, respectively. Personality traits were assessed using the extroversion/introversion subscale of the Eysenck Personality Inventory. Descriptive statistics, t-test, one-way analysis of variance (ANOVA), Pearson’s correlation analysis, and multiple linear regressions were used to determine the predictors of the main research variables. Results The prevalence of mild, moderate, and severe compassion fatigue in 221 nursing interns (mean age 21 years, 202 [91.4%] females) was 10.4%, 46.6%, and 43.0%, respectively, and their mean scores for CS, BO, and STS were 29.75 ± 6.39, 28.72 ± 4.78, and 28.51 ± 7.51, respectively. Psychological resilience and empathy were the strongest protective factors for CS and BO, respectively (p

Dynamic imaging of optical remote sensing satellites refers to the active acquisition of images while the satellite is maneuvering at a high angular velocity, which significantly enhances the efficiency and application value of remote sensing imagery. However, due to the influence of rapid maneuvering, the random error of star sensors significantly increases, resulting in a decrease in the geometric positioning accuracy of dynamic imaging remote sensing images. This paper proposes a dynamic fusion method for multisource attitude measurement data based on the noise adaptive estimation and bidirectional filter to achieve high-precision attitude determination and geometric positioning in dynamic imaging. Based on the measurement error model of star sensors, the weights of the star sensor and gyroscope are adaptively adjusted in multisource data fusion to reduce the impact of star sensor measurement errors on the gyroscope. Moreover, a bidirectional fusion filter that includes a low-velocity maneuvering stage is proposed to realize the optimal estimation of the satellite attitude parameter. The simulation data and onboard data of the Luojia3-01 (LJ3–01) satellite were tested to verify the effectiveness of the proposed method. The geometric positioning accuracy of the staring images of LJ3–01 improved from 10.048 m to 7.538 m. The registration accuracy of the sequential images improved from 3.568 pixels to 1.179 pixels. The proposed method can significantly improve the attitude determination accuracy and the geometric positioning accuracy of LJ3–01 satellite staring images. Moreover, for simulation data with various angular velocities, the attitude determination accuracies of the proposed method are better than 0.93”. The experimental results show that the proposed method can achieve high-precision attitude determination in dynamic imaging, reaching the accuracy in the traditional passive imaging.

Abstract Background The hippocampus, with its complex subfields, is linked to numerous neuropsychiatric traits. While most research has focused on its global structure or a few specific subfields, a comprehensive analysis of hippocampal substructures and their genetic correlations across a wide range of neuropsychiatric traits remains underexplored. Given the hippocampus’s high heritability, considering hippocampal and subfield volumes (HASV) as endophenotypes for neuropsychiatric conditions is essential. Methods We analyzed MRI-derived volumetric data of hippocampal and subfield structures from 41,525 UK Biobank participants. Genome-wide association studies (GWAS) on 24 HASV traits were conducted, followed by genetic correlation, overlap, and Mendelian randomization (MR) analyses with 10 common neuropsychiatric traits. Polygenic risk scores (PRS) based on HASV traits were also evaluated for predicting these traits. Results Our analysis identified 352 independent genetic variants surpassing a significance threshold of 2.1 × 10−9 within the 24 HASV traits, located across 93 chromosomal regions. Notably, the regions 12q14.3, 17q21.31, 12q24.22, 6q21, 9q33.1, 6q25.1, and 2q24.2 were found to influence multiple HASVs. Gene set analysis revealed enrichment of neural differentiation and signaling pathways, as well as protein binding and degradation. Of 240 HASV-neuropsychiatric trait pairs, 75 demonstrated significant genetic correlations (P

Obesity， as a global health issue， presents significant challenges in its treatment and management， particularly the phenomenon of weight regain. This not only undermines the effectiveness of weight loss efforts but may also have further impacts on the physical and mental health of patients. This article delves into the issue of weight regain during the treatment of obesity， analyzing its definition， prevalence， and health implications. It elucidates the biological mechanisms of weight regain from aspects such as the body weight set-point theory， metabolic adaptation， immune cell phenotypic changes， lipid metabolism， and appetite regulation. A comprehensive management strategy is proposed， including lifestyle adjustments， continuous pharmacological treatment， surgical intervention， and multidisciplinary collaboration， aiming to achieve long-term weight control in obese patients. The study emphasizes the continuity and individualization of weight management， providing scientific guidance for clinical practice.

Abstract Antioxidant capacity is an important indicator for evaluating the growth and developmental quality of rice. This study has guiding significance for the cultivation of high-nutrient-value varieties. To investigate the molecular mechanisms underlying the antioxidant characteristics of rice grains after the filling stage, Yangzinuo 1 (YZN1) was used as the experimental material, and grains collected at five different time points (7 days apart) after the filling stage were used for transcriptome sequencing. Through weighted gene coexpression network analysis (WGCNA), a coexpression network of gene weights related to antioxidant characteristics was constructed. LOC_Os10g39140, LOC_Os10g38276, and LOC_Os05g45740 were identified from the 2 modules showing the highest correlations with the target traits. GO functional annotation showed that target modules were enriched in pathways related to phenylalanine, flavonoids, and other related pathways, such as GO:0006558, GO:0006559, GO:0009812, and GO:0009813. Correlation analysis with metabolites revealed that differentially expressed genes were significantly enriched in pathways related to antioxidant characteristics and energy metabolism processes, such as glycolysis/gluconeogenesis and flavonoid biosynthesis. The core genes identified in this study were found to be highly correlated with antioxidant characteristics and enriched in pathways related to metabolic and energy pathways and molecular activities. These results provide an effective dataset supporting breeding targeting functional rice characteristics.

Abstract Objective Brain arteriovenous malformations (BAVMs) represent an ongoing clinical challenge because of their complex nature. The long-term outcomes of BAVMs patients treated with stereotactic radiosurgery (SRS) alone are unclear. Methods We conducted a retrospective analysis of 201 patients treated for BAVMs from January 2010 to December 2019. The identified predictors of obliteration or hemorrhage in the multivariate analysis were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). Results A total of 201 patients treated with gamma knife radiosurgery (GKRS) alone as the primary treatment for BAVMs were included. The mean age at GKRS treatment was 31.4 ± 1.1 years, and 61.2% of the patients were male. Multivariate logistic regression revealed that a higher radiosurgery-based AVM score (OR 1.847, 95% CI = 1.292–2.641; p = 0.001) was significantly associated with worse obliteration, and a higher margin dose significantly favored obliteration (OR 0.352, 95% CI = 0.189–0.658; p = 0.001). Multivariate analysis revealed that an increased lesion volume of 1 cm3 (OR 1.279, 95% CI = 1.023–1.600; p = 0.031) and a high margin dose (OR 0.363, 95% CI = 0.134–0.983; p = 0.046) were significant prognostic factors for post-SRS hemorrhage. Conclusions In conclusion, our study investigated the available clinical and radiological prognostic factors for BAVMs and revealed that a higher margin dose significantly improved both the obliteration rate and nonhemorrhagic outcomes. Currently, the most appropriate candidates, Spetzler-Martin grade, and optimal radiation dose are still being defined by prospective trials.

Abstract Background Lipid management based on cardiovascular risk level is the cornerstone of primary prevention of coronary artery disease (CAD), while the accuracy and adherence of traditional cardiovascular risk stratification have been questioned. Prevention strategies based on imaging screening for atherosclerotic plaques are found to be more objective and adherent in recent studies. This trial aims to investigate the role of coronary computed tomography angiography (CCTA) in guiding the primary prevention of CAD in a randomized controlled design. Methods Approximately 3400 middle-aged asymptomatic community participants will be recruited and randomized in a 1:1 ratio to a traditional cardiovascular risk score-guided (usual care group) or CCTA-guided (CCTA group) strategy. Participants with cardiovascular disease, prior lipid-lowering therapy, CCTA contraindication, or serious diseases that affect life span will be excluded. The intervention strategy includes blood pressure, blood glucose, and lipid management and lifestyle modifications. Blood pressure and glucose targets and lifestyle modification recommendations keep the same in both strategies, while lipid management is personalized based on traditional risk level or CCTA results, respectively. The primary outcome is the proportion of participants taking lipid-lowering medication regularly at both 6 and 12 months. The secondary outcomes include the proportion of participants achieving low-density lipoprotein cholesterol lowering targets at 12 months, mean changes in lipid levels from baseline to 12 months, barriers to adherence, adverse reactions related to CCTA examination, and cardiovascular events. Discussion The study is the first randomized clinical trial to examine the effectiveness of a CCTA-guided versus a traditional risk score-guided primary prevention strategy in an asymptomatic community-based population. Trial registration ClinicalTrials.gov NCT05725096. Registered on 2 February 2023.

Abstract Purpose To evaluate the long-term efficacy and safety of GP and TPF sequential chemotherapy regimens in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Methods From 2005 to 2016, a total of 408 LA-NPC patients treated with GP or TPF sequential chemoradiotherapy were retrospectively included. Propensity Score Matching (PSM) was employed to balance the baseline variables. Survival outcomes and acute toxicities were compared between both groups. Results A total of 230 patients were selected by 1:1 PSM. At a median follow-up of 91 months, no significant differences were observed between the matched GP and TPF groups regarding 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregionally relapse-free survival (83.4% vs. 83.4%, P = 0.796; 75.6% vs. 68.6%, P = 0.301; 86.7% vs. 81.1%, P = 0.096; and 87.4% vs. 87.2%, P = 0.721). Notable disparities in adverse effects were identified, with higher incidences of grade 3/4 thrombocytopenia in the GP group while grade 3/4 leukopenia and neutropenia in the TPF group. Though not recorded in our cohort, combined with the FAERS database, thrombotic adverse reactions are a concern for the GP regimen, while the TPF regimen requires vigilance for life-threatening adverse reactions such as septic shock, acute respiratory distress syndrome, and laryngeal edema. Conclusion No significant difference in long-term outcomes was observed between the GP and TPF sequential chemotherapy regimens for LA-NPC. Differences in adverse effects should be noted when choosing the regimen.

Abstract Objectives To explore the performance differences of multiple annotations in radiomics analysis and provide a reference for tumour annotation in large-scale medical image analysis. Methods A total of 342 patients from two centres who underwent radical resection for rectal cancer were retrospectively studied and divided into training, internal validation, and external validation cohorts. Three predictive tasks of tumour T-stage (pT), lymph node metastasis (pLNM), and disease-free survival (pDFS) were performed. Twelve radiomics models were constructed using Lasso-Logistic or Lasso-Cox to evaluate and four annotation methods, 2D detailed annotation along tumour boundaries (2D), 3D detailed annotation along tumour boundaries (3D), 2D bounding box (2DBB), and 3D bounding box (3DBB) on T2-weighted images, were compared. Radiomics models were used to establish combined models incorporating clinical risk factors. The DeLong test was performed to compare the performance of models using the receiver operating characteristic curves. Results For radiomics models, the area under the curve values ranged from 0.627 (0.518–0.728) to 0.811 (0.705–0.917) in the internal validation cohort and from 0.619 (0.469–0.754) to 0.824 (0.689–0.918) in the external validation cohort. Most radiomics models based on four annotations did not differ significantly, except between the 3D and 3DBB models for pLNM (p = 0.0188) in the internal validation cohort. For combined models, only the 2D model significantly differed from the 2DBB (p = 0.0372) and 3D models (p = 0.0380) for pDFS. Conclusion Radiomics and combined models constructed with 2D and bounding box annotations showed comparable performances to those with 3D and detailed annotations along tumour boundaries in rectal cancer characterisation and prognosis prediction. Critical relevance statement For quantitative analysis of radiological images, the selection of 2D maximum tumour area or bounding box annotation is as representative and easy to operate as 3D whole tumour or detailed annotations along tumour boundaries. Key Points There is currently a lack of discussion on whether different annotation efforts in radiomics are predictively representative. No significant differences were observed in radiomics and combined models regardless of the annotations (2D, 3D, detailed, or bounding box). Prioritise selecting the more time and effort-saving 2D maximum area bounding box annotation. Graphical Abstract

Abstract Based on our previous findings that salicylic acid and jasmonic acid increased Nostoc flagelliforme polysaccharide yield by regulating intracellular nitric oxide (NO) levels, the mechanism through which NO affects polysaccharide biosynthesis in Nostoc flagelliforme was explored from the perspective of S-nitrosylation (SNO). The addition of NO donor and scavenger showed that intracellular NO had a significant positive effect on the polysaccharide yield of N. flagelliforme. To explore the mechanism, we investigated the relationship between NO levels and the activity of several key enzymes involved in polysaccharide biosynthesis, including fructose 1,6-bisphosphate aldolase (FBA), glucokinase (GK), glucose 6-phosphate dehydrogenase (G6PDH), mitochondrial isocitrate dehydrogenase (ICDH), and UDP-glucose dehydrogenase (UGDH). The enzymatic activities of G6PDH, ICDH, and UGDH were shown to be significantly correlated with the shifts in intracellular NO levels. For further validation, G6PDH, ICDH, and UGDH were heterologously expressed in Escherichia coli and purified via Ni+-NAT affinity chromatography, and subjected to a biotin switch assay and western blot analysis, which revealed that UGDH and G6PDH were susceptible to SNO. Furthermore, mass spectrometry analysis of proteins treated with S-nitrosoglutathione (GSNO) identified the SNO modification sites for UGDH and G6PDH as cysteine 423 and cysteine 249, respectively. These findings suggest that NO modulates polysaccharide biosynthesis in N. flagelliforme through SNO of UGDH and G6PDH. This reveals a potential mechanism through which NO promotes polysaccharide synthesis in N. flagelliforme, while also providing a new strategy for improving the industrial production of polysaccharides.

Amino acid metabolic remodeling is a hallmark of cancer, driving an increased nutritional demand for amino acids. Amino acids are pivotal for energetic regulation, biosynthetic support, and homeostatic maintenance to stimulate cancer progression. However, the role of phenylalanine in multiple myeloma (MM) remains unknown. Here, we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow (BM) cells. After the treatment, phenylalanine levels increase in plasma and decrease in BM. This suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM progression. The requirement for phenylalanine by MM cells exhibits a similar pattern. Inhibiting phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib (BTZ) treatment in vitro and murine models. Mechanistically, phenylalanine deprivation induces excessive endoplasmic reticulum stress and leads to MM cell apoptosis through the ATF3–CHOP–DR5 pathway. Interference with ATF3 significantly affects phenylalanine deprivation therapy. In conclusion, we have identified phenylalanine metabolism as a characteristic feature of MM metabolic remodeling. Phenylalanine is necessary for MM proliferation, and its aberrant demand highlights the importance of low-phenylalanine diets as an adjuvant treatment for MM.

BackgroundThe senescence of alveolar type II epithelial cells is an important driving factor for the progression of silicotic fibrosis, and the regulatory effects of oxamate on the senescence of alveolar type II epithelial cells is still unclear.ObjectiveTo explore whether lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting senescence of alveolar type II epithelial cellsMethodsThis study was divided into two parts: in vivo experiments and in vitro experiments. In the first part, forty SPF C57BL/6J male mice were randomly divided into four groups with 10 in each group: control group, silicosis model group, low-dose oxamate treatment group, and high-dose oxamate treatment group. The silicotic mouse model was established by intratracheal instillation of 50 μL SiO2 suspension (100 mg·mL−1). The treatment models were prepared by intraperitoneal injection of 100 μL oxamate (225 mmol·L−1 and 1125 mmol·L−1). In the second part, induction of MLE-12 mouse alveolar type II epithelial cells was conducted with SiO2. The in vitro experimental groups were ① SiO2 induction groups: control group, 50 μg·mL−1 SiO2 group, 100 μg·mL−1 SiO2 group, and 200 μg·mL−1 SiO2 group, and ② oxamate treatment groups: control group, SiO2 group (100 μg·mL−1), low-dose oxamate (25 mmol·L−1) treatment group, and high-dose oxamate (50 mmol·L−1) treatment group. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after sirius red staining; positive co-expression of prosurfactant protein C (Pro-SPC) and β-galactosidase was detected by immunofluorescence staining; positive expression of β-galactosidase in MLE-12 cells was detected by immunofluorescence staining. The protein expression levels of collagen type I (CoL I), fibronectin1 (FN1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), lactate dehydrogenase A (LDHA), p-ataxia telangiectasia and Rad3-related kinase (ATR), and cyclin-dependent kinase inhibitors p21, and p16 were detected by Western blotting.ResultsCompared with the control group, the protein expression levels of HK2, PKM2, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group and the SiO2-induced MLE-12 cells (P＜0.05). The in vivo studies showed that, compared with the control group, the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the protein expression levels of CoL I, FN1, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group (P＜0.05). Compared with the silicosis model group, the oxamate treatment groups showed significant downregulation of the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the the CoL I, FN1, LDHA, p-ATR, p21, and p16 protein expression levels, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). The in vitro studies showed that, compared with the control group, the proportion of β-galactosidase positive cells and the protein expression levels of p-ATR, p21, and p16 were significantly upregulated in the SiO2-induced group (P＜0.05). Compared with the SiO2 group, the proportion of β-galactosidase positive cells and the LDHA, p-ATR, p21 and p16 protein expression levels were significantly downregulated in the oxamate treatment groups, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05).ConclusionLactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting the senescence of alveolar type II epithelial cells.

Abstract Background Selenium nanoparticles (SeNPs) are increasingly gaining attention due to its characteristics of low toxicity, high activity, and stability. Additionally, Bacillus licheniformis, as a probiotic, has achieved remarkable research outcomes in diverse fields such as medicine, feed processing, and pesticides, attracting widespread attention. Consequently, evaluating the activity of probiotics and SeNPs is paramount. The utilization of probiotics to synthesize SeNPs, achieving large-scale industrialization, is a current hotspot in the field of SeNPs synthesis and is currently the most promising synthetic method. To minimize production costs and maximize yield of SeNPs, this study selected agricultural by-products that are nutrient-rich, cost-effective, and readily available as culture medium components. This approach not only fulfills industrial production requirements but also mitigates the impact on downstream processes. Results The experimental findings revealed that SeNPs synthesized by B. licheniformis F1 exhibited a spherical morphology with diameters ranging from 110 to 170 nm and demonstrating high stability. Both the secondary metabolites of B. licheniformis F1 and the synthesized SeNPs possessed significant free radical scavenging ability. To provide a more robust foundation for acquiring large quantities of SeNPs via fermentation with B. licheniformis F1, key factors were identified through single-factor experiments and response surface methodology (RSM) include a 2% seed liquid inoculum, a temperature of 37 ℃, and agitation at 180 rpm. Additionally, critical factors during the optimization process were corn powder (11.18 g/L), soybean meal (10.34 g/L), and NaCl (10.68 g/L). Upon validating the optimized conditions and culture medium, B. licheniformis F1 can synthesize nearly 100.00% SeNPs from 5 mmol/L sodium selenite. Subsequently, pilot-scale verification in a 5 L fermentor using the optimized medium resulted in a shortened fermentation time, significantly reducing production costs. Conclusion In this study, the efficient production of SeNPs by the probiotic B. licheniformis F1 was successfully achieved, leading to a significant reduction in fermentation costs. The exploration of the practical applications of this strain holds significant potential and provides valuable guidance for facilitating the industrial-scale implementation of microbial synthesis of SeNPs.

Abstract The genetic contribution of protein-coding variants to immune-mediated diseases (IMDs) remains underexplored. Through whole exome sequencing of 40 IMDs in 350,770 UK Biobank participants, we identified 162 unique genes in 35 IMDs, among which 124 were novel genes. Several genes, including FLG which is associated with atopic dermatitis and asthma, showed converging evidence from both rare and common variants. 91 genes exerted significant effects on longitudinal outcomes (interquartile range of Hazard Ratio: 1.12-5.89). Mendelian randomization identified five causal genes, of which four were approved drug targets (CDSN, DDR1, LTA, and IL18BP). Proteomic analysis indicated that mutations associated with specific IMDs might also affect protein expression in other IMDs. For example, DXO (celiac disease-related gene) and PSMB9 (alopecia areata-related gene) could modulate CDSN (autoimmune hypothyroidism-, psoriasis-, asthma-, and Graves’ disease-related gene) expression. Identified genes predominantly impact immune and biochemical processes, and can be clustered into pathways of immune-related, urate metabolism, and antigen processing. Our findings identified protein-coding variants which are the key to IMDs pathogenesis and provided new insights into tailored innovative therapies.

Abstract Coiled-coil domain containing 88C (CCDC88C) is a component of non-canonical Wnt signaling, and its dysregulation causes colorectal cancer metastasis. Dysregulated expression of CCDC88C was observed in lymph node metastatic tumor tissues of breast cancer. However, the role of CCDC88C in breast cancer metastasis remains unclear. To address this, the stable BT549 and SKBR3 cell lines with CCDC88C overexpression or knockdown were developed. Loss/gain-of-function experiments suggested that CCDC88C drove breast cancer cell motility in vitro and lung and liver metastasis in vivo. We found that CCDC88C led to c-JUN-induced transcription activation. Overlapping genes were identified from the genes modulated by CCDC88C and c-JUN. CEMIP, one of these overlapping genes, has been confirmed to confer breast cancer metastasis. We found that CCDC88C regulated CEMIP mRNA levels via c-JUN and it exerted pro-metastatic capabilities in a CEMIP-dependent manner. Moreover, we identified the CCDC88C as a substrate of polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6). GALNT6 was positively correlated with CCDC88C protein abundance in the normal breast and breast cancer tissues, indicating that GALNT6 might be associated with expression patterns of CCDC88C in breast cancer. Our data demonstrated that GALNT6 maintained CCDC88C stability by promoting its O-linked glycosylation, and the modification was critical for the pro-metastatic potential of CCDC88C. CCDC88C also could mediate the pro-metastatic potential of GALNT6 in breast cancer. Collectively, our findings uncover that CCDC88C may increase the risk of breast cancer metastasis and elucidate the underlying molecular mechanisms.

AIM: To determine the factors related to preoperative ocular characters that are predictive of insufficient vault (

Abstract Red rice is a kind of whole grain with health benefits. Probiotic fermentation is widely applied to promote nutrient release from cereals and improve bioactivity. The study aims to investigate the impact of Lactiplantibacillus plantarum (L. plantarum) dy‐1 fermentation on the bioactivities, bioaccessibility, and lipid‐lowering activities of red rice. Results indicated that fermentation significantly increased the protein and total phenolic content by 1.7 and 1.4 times of red rice, as well as the content of essential and nonessential amino acids. Fermentation remarkably increased the bioaccessibility of phenolics and the antioxidant capacity of red rice during in vitro digestion. Additionally, Caenorhabditis elegans study revealed that fermented red rice extract reduced the triglyceride content, alleviated fat deposition, and regulated lipid metabolism by altering the genes in the fatty acid oxidation and synthesis, such as daf‐16, mdt‐15, nhr‐49, fat‐5, fat‐7, and hosl‐1. Therefore, L. plantarum dy‐1 fermentation was beneficial for improving bioaccessibility and lipid‐lowering activities of red rice, which will provide a reference for utilization of red rice as a functional food.

Abstract In modern tunnel construction, TBM (Tunnel Boring Machine) plays a very important role. In response to the needs of tunnel wall reinforcement and TBM automated construction for tunnel construction, a shotcrete mechanism mounted on the TBM is designed. In order to evaluate the kinematic performance of the mechanism, this paper studies the forward and inverse kinematics and spatial architecture of the TBM shotcrete robot. Firstly, based on the D–H parameter method, the number of joints and links is determined and structural analysis is performed to obtain the robot's forward kinematics equation, achieving the mapping between joint space and pose space. Then, by determining the joint variables, the mapping of the end tool in Cartesian space is achieved. Finally, based on the Monte Carlo random sampling method, the workspace of the robot is constructed, and its reachability and flexibility within the robot workspace are evaluated. The performance of the device is verified by building a prototype, which meets the requirements well. Through the research in this paper, it can provide theoretical basis and guidance for the design and control of the shotcrete robot.

Abstract Background Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. Methods Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. Results A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88–0.95, P = 2.92 × 10−7) and Europe (OR = 0.92, 95%CI 0.88–0.95, P = 4.61 × 10−6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. Conclusion Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Abstract Multiple myeloma (MM) denotes a cancerous growth characterized by abnormal proliferation of plasma cells. Growing evidence suggests that the complexity in addressing MM lies in the presence of minimal residual disease (MRD) within the body. MRD assessment is becoming increasingly important for risk assessment in patients with MM. Similarly, the levels of serum free protein light chain and their ratio play a crucial role in assessing the disease burden and changes in MM. In this paper, we review and explore the utilization of MRD and serum free light chain ratio in the treatment of MM, delving into their respective characteristics, advantages, disadvantages, and their interrelation.

Abstract Background Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population. Methods To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS148); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS183); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRSGenomewide). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants. Results Three trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS183 demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose–response effect of PRS183 on incident colorectal neoplasms. Incorporating PRS183 with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32). Conclusions Our comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity. Graphical Abstract

To elucidate the influence of different concentrations of carrageenan (CA, 0.4%, 0.8%, 1.2%, 1.6%, 2.0%, w/w) on the gelation properties and structure of hemp protein isolate (HPI), with the hemp protein isolate without adding CA as the control, the water-holding capacity, texture, rheological properties of the composite gels were determined. Meanwhile, the effect of CA addition on the water distribution, protein structure and intermolecular forces in the composite gels was also investigated. The results showed that the addition of CA significantly (P

Abstract Background This study leverages a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between 1,400 metabolites and pulmonary fibrosis, using genetic variation as instrumental variables. By adhering to stringent criteria for instrumental variable selection, the research aims to uncover metabolic pathways that may influence the risk and progression of pulmonary fibrosis, providing insights into potential therapeutic targets. Methods Utilizing data from the OpenGWAS project, which includes a significant European cohort, and metabolite GWAS data from the Canadian Longitudinal Aging Study (CLSA), the study employs advanced statistical methods. These include inverse variance weighting (IVW), weighted median estimations, and comprehensive sensitivity analyses conducted using the R software environment to ensure the robustness of the causal inferences. Results The study identified 62 metabolites with significant causal relationships with pulmonary fibrosis, highlighting both risk-enhancing and protective metabolic factors. This extensive list of metabolites presents a broad spectrum of potential therapeutic targets and biomarkers for early detection, underscoring the metabolic complexity underlying pulmonary fibrosis. Conclusions The findings from this MR study significantly advance our understanding of the metabolic underpinnings of pulmonary fibrosis, suggesting that alterations in specific metabolites could influence the risk and progression of the disease. These insights pave the way for the development of novel diagnostic and therapeutic strategies, emphasizing the potential of metabolic modulation in managing pulmonary fibrosis.

Objectives: Emerging evidence suggests that N6-methyladenosine (m 6 A) methylation plays a critical role in cancers through various mechanisms. This work aims to reveal the essential role of m 6 A methylation “readers” in regulation of cancer prognosis at the pan-cancer level. Methods: Herein, we focused on one special protein family of the “readers” of m 6 A methylation, YT521-B homology (YTH) domain family genes, which were observed to be frequently dysregulated in tumor tissues and closely associated with cancer prognosis. Then, a comprehensive analysis of modulation in cancer prognosis was conducted by integrating RNA sequencing (RNAseq) datasets of YTH family genes and clinical information at the pan-cancer level. Results: YTH family genes were significantly differentially expressed in most of the cancers, particularly increased in Gastrointestinal cancers, and decreased in Endocrine and Urologic cancers. In addition, they were observed to be associated with overall survival (OS) and disease-specific survival (DSS) with various extent, especially in lower grade glioma (LGG), thyroid cancer (THCA), liver hepatocellular carcinoma (LIHC) and kidney clear cell carcinoma (KIRC), so were some “writers” (METLL3, METLL14, WTAP) and “erasers” (FTO, ALKBH5). Further survival analysis illustrated that YTH family genes specifically YTHScore constructed by combining 5 YTH family genes, as well as RWEScore calculated by combining genes from “readers”-“writers”-“erasers” could dramatically distinguish tumor prognosis in 4 representative cancers. As expected, YTHScore presented an equally comparable prognostic classification with RWEScore. Finally, analysis of immune signatures and clinical characteristics implied that, the activity of the innate immune, diagnostic age, clinical stage, Tumor-Node-Metastasis (TNM) stage and immune types, might play specific roles in modulating tumor prognosis. Conclusions: The study demonstrated that YTH family genes had the potential to predict tumor prognosis, in which the YTHScore illustrated equal ability to predict tumor prognosis compared to RWEScore, thus providing insights into prognostic biomarkers and therapeutic targets at the pan-cancer level.

Background Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is an uncommon ocular motor disorder which is featured by binocular exotropia and bilateral internuclear ophthalmoplegia.Methods A 71-year-old man with hypertension presented to the emergency department with sudden-onset diplopia. Neurological examination, neuroimaging, blood and cerebrospinal fluid (CSF) testing were performed.Results We presented a typical WEBINO syndrome case with a clear dorsal pontine infarction involving bilateral medial longitudinal fasciculi (MLF) on brain MR scan. The patient’s eye movement abnormalities improved and MR lesions disappeared at 60-day follow-up after treatment of clopidogrel and atorvastatin. Furthermore, we summarised the aetiology and pathophysiology of WEBINO by retrospectively analysing all published WEBINO cases. We found that WEBINO can result from various underlying pathologies, with inflammation most common in the young, and stroke most common in the elderly. Simultaneous lesions of bilateral MLF definitely contribute to the pathophysiology of WEBINO.Conclusions This case underscores the importance of early recognising WEBINO in the emergency department. A timely diagnosis of stroke-induced WEBINO is important so that acute treatment can be considered and for initiating secondary stroke preventive measures to potentially improve the prognosis.

ABSTRACT Klebsiella pneumoniae is a common pathogen of nosocomial infection, which can cause pneumonia, urinary tract infection, cystitis, and bloodstream infections (BSIs). Here, we genetically characterize a novel carbapenem-resistant K. pneumoniae (CRKP) strain recovered from the blood of a 44-year-old male patient with severe acute necrotizing pancreatitis and septic shock in China. The strain is a ST45 K. pneumoniae with a novel serotype of K43, named 18SHX166. The susceptibility testing results showed that 18SHX166 was resistant to cephalosporin and carbapenems but still susceptible to ceftazidime-avibactam, quinolones, colistin, and amikacin. Genomic sequencing revealed that 18SHX166 contains three plasmids, namely pSHX166-Hv, pSHX166-KPC, and pSHX166-3. pSHX166-Hv harbored the iucABCD operon, encoding the siderophore of aerobactin. pSHX166-KPC harbored blaKPC-2 gene and possessed complete conjugative regions. The conjugation experiment verified pSHX166-KPC as a self-transmissible plasmid mediating the dissemination of antibiotic resistance, with a conjugation rate of 2.21 × 10−5. Additionally, the growth curve showed that 18SHX166 demonstrates a higher growth rate than the control strains. The characteristics of 18SHX166 indicate a potential high risk of clinical transmission.IMPORTANCEST45-K43 carbapenem-resistant Klebsiella pneumoniae isolate, 18SHX166, carries a carbapenem resistance plasmid and virulence plasmid. It has the characteristics of multidrug resistance, high transmissibility, and a fast growth rate, which could pose a threat to the control of antimicrobial resistance and clinical transmission, causing a severe challenge to public health.

The increasing prevalence of non-tuberculous mycobacterium (NTM) infections alongside tuberculosis (TB) underscores a pressing public health challenge. Yet, the mechanisms governing their infection within the lung remain poorly understood. Here, we integrate metagenomic sequencing, metabolomic sequencing, machine learning classifiers, SparCC, and MetOrigin methods to profile bronchoalveolar lavage fluid (BALF) samples from NTM/TB patients. Our aim is to unravel the intricate interplay between lung microbial communities and NTM/Mycobacterium tuberculosis infections. Our investigation reveals a discernible reduction in the compositional diversity of the lung microbiota and a diminished degree of mutual interaction concomitant with NTM/TB infections. Notably, NTM patients exhibit a distinct microbial community characterized by marked specialization and notable enrichment of Pseudomonas aeruginosa and Staphylococcus aureus, driving pronounced niche specialization for NTM infection. Simultaneously, these microbial shifts significantly disrupt tryptophan metabolism in NTM infection, leading to an elevation of kynurenine. Mycobacterium intracellulare, Mycobacterium paraintracellulare, Mycobacterium abscessus, and Pseudomonas aeruginosa have been implicated in the metabolic pathways associated with the conversion of indole to tryptophan via tryptophan synthase within NTM patients. Additionally, indoleamine-2,3-dioxygenase converts tryptophan into kynurenine, fostering an immunosuppressive milieu during NTM infection. This strategic modulation supports microbial persistence, enabling evasion from immune surveillance and perpetuating a protracted state of NTM infection. The elucidation of these nuanced microbial and metabolic dynamics provides a profound understanding of the intricate processes underlying NTM and TB infections, offering potential avenues for therapeutic intervention and management.

BackgroundTumor antigen peptide vaccines have shown remarkable efficacy, safety, and reliability in recent studies. However, the screening process for immunopotent antigenic peptides is cumbersome, limiting their widespread application. Identifying neoantigen peptides that can effectively trigger an immune response is crucial for personalized cancer treatment.MethodsWhole exome sequencing was performed on patient-derived colon cancer cells to predict 9-amino-acid (9aa) neoantigen peptides. In vitro simulation of endogenous antigen presentation by antigen-presenting cells (dendritic cells) to CD8+ T cells was conducted, aiming to activate the CD8+ immune response to the predicted antigens. The immunological effects of each neoantigen were assessed using flow cytometry and ELISpot assays, while the relationship between neoantigen immunogenicity and MHC molecular affinity was examined.Results1. Next-generation sequencing (NGS) predicted 9-amino acid (9aa) neoantigen peptides for subsequent immunological analysis.2. Higher mDC Levels in Experimental Group: CD11c+CD83+ mature dendritic cells (mDCs) were 96.6% in the experimental group, compared to 0.051% in the control group. CD80 fluorescence intensity was also significantly higher in the experimental group, confirming a greater mDC presence.3. Neoantigen Peptides Promote CD4+, CD8+ T, and NK Cell Proliferation: After 14 days, flow cytometry showed higher percentages of CD4+ T (37.41% vs 7.8%), CD8+ T (16.67% vs 14.63%), and NK cells (33.09% vs 7.81%) in the experimental group, indicating that the neoantigen peptides induced proliferation of CD4+, CD8+ T cells, and NK cells. 4. The results, analyzed using two-way ANOVA, showed that the standardized T-value for HLA molecular affinity variation in the 1-4 range (Group B) was significantly higher than for ≤1 (Group A, p < 0.0001) and >4 (Group C, p < 0.05). Regarding HLA-allele genotypes, HLA-Type 1 had a significantly higher standardized T-value than HLA-Type 2 (p < 0.05) and HLA-Type 3 (p < 0.0001). HLA-Type 1 was identified as the allele associated with the highest T-value.Conclusion1. The most immunogenic neoantigens typically exhibit an MHC molecular affinity variation between 1 and 4, indicating that stronger immunogenicity correlates with higher MHC molecular affinity variation. 2. Each patient's HLA molecules were classified into Types 1, 2, and 3, with Type 1 showing the highest binding capacity for neoantigens. Our findings indicate that the most immunogenic neoantigens were associated with HLA Type 1. 3. Neoantigen peptides were shown to activate the proliferation of both CD8+ T-cells and induce proliferation of CD4+ T-cells and NK cells. 4. Variation in MHC molecular affinity and HLA neoantigen genotype are anticipated to serve as valuable variables for screening highly immunogenic neoantigens, facilitating more efficient preparation of effective polypeptide tumor vaccines.

The evolution of flexible Zn‐ion batteries (FZIBs) significantly hinges on the development of gel electrolytes, characterized by their mechanical properties, ionic conductivity, and environmentally friendly production processes. The prevailing challenge in this domain has been devising a gel electrolyte that encapsulates all these critical attributes effectively for practical application. This study presents a novel zinc ion gel (Zn‐gel) electrolyte developed for FZIBs, synthesized via ethanol vapor‐induced assembly of cellulose molecules. This innovative process fosters significant hydrogen bonding and ion‐complexation with Zn2+ ions, resulting in a gel with exceptional mechanical strength (0.88 MPa), high ion transference (over 0.7), and impressive ionic conductivity (8.39 mS cm−1). The Zn‐gel enables a FZIB to achieve a reversible capacity of 207.3 mAh g−1 and over 93% Coulombic efficiency after 500 cycles, devoid of liquid electrolyte. Highlighting a promising route for high‐performance, eco‐friendly gel electrolytes, this research advances flexible electronics and portable device applications, demonstrating the profound potential of bio‐based polymers in enhancing energy storage technology.

Glucose is a major energy substrate for cellular life activities, and its metabolic pathways include glycolysis, the pentose phosphate pathway, the hexosamine biosynthesis pathway, and the polyol pathway. Here, we review the glucose uptake pathways, metabolic characteristics, glucose transport, glucose metabolism-related enzymes, and biological importance in mammalian oocyte maturation, early embryo development, and embryonic stem cell proliferation and differentiation. Moreover, the interrelationships among glucose metabolism, female reproduction-related diseases and assisted reproductive technologies are focused. In addition, we review a number of analytical methodologies with the intention to integrate a multi-tiered strategy that encompasses cutting-edge metabolomics, artificial intelligence, epigenetics, and morphological assessments, setting the stage for a pivotal approach to cultivating high-caliber embryos in the future.

Abstract Invertebrates greatly support the growth, development, and reproduction of insectivorous birds. However, the influence of human activity (e.g., pesticide use, deforestation, and urbanization) inevitably leads to a decrease in global arthropods. The diversity and variation in invertebrate diet influence the food composition of birds, especially species living in rapidly changing environments, such as the Tibetan Plateau. However, little is known of the seasonal variation in invertebrate diet in response to environmental changes. Here, we characterized the invertebrate diet composition in pre‐ and post‐breeding black‐necked crane (Grus nigricollis) using fecal metabarcoding. We identified 38 invertebrate genera; the top three were Tipula (82.1% of relative abundance), Ceramica (3.0%), and unclassified_Hymenoptera (2.5%), with Tipula predominated the diet in both seasons. We also observed 20 and 16 unique genera in the pre‐ and post‐breeding periods, and the genera composition was distinct between seasons (R = .036, p = .024). In pre‐breeding, black‐necked cranes tended to consume more diverse foods, and individual cranes exhibited greater heterogeneity at the genus level. At the genera and species level, pre‐breeding black‐necked cranes showed a wider dietary niche than post‐breeding cranes. We observed season‐specific features, with Tipula (common crane fly) and Stethophyma (grasshoppers) being enriched in the post‐breeding period and Ceramica (moth) being more abundant in the pre‐breeding period. Three Tipula species had the greatest importance in discriminating between seasonal diets. This study demonstrated a seasonal pattern of invertebrate diet in the black‐necked crane, suggesting diet composition in response to resource and species availability. These results elaborate on the foraging ecology of highland birds and can inform the management of black‐necked crane conservation.

Abstract Venetoclax, a small molecule inhibitor of BCL‐2, has demonstrated efficacy in treating acute leukemias and has been recommended as one of the first‐line anti‐leukemia therapies. Although venetoclax has been suggested to probably possess the ability to penetrate the central nervous system (CNS), current data to elucidate the characteristics of venetoclax in cerebrospinal fluid (CSF), bone marrow (BM), and plasma are still lacking. This study investigated the real‐world characteristics of venetoclax concentrations in CSF, BM, and plasma in acute leukemia patients. Thirteen acute leukemia patients treated with venetoclax were included, with paired samples of CSF, BM, and plasma collected and venetoclax concentrations measured using LC–MS/MS. With the results, the median venetoclax concentrations were 2030 ng/mL in plasma, 16.7 ng/mL in CSF, and 1390 ng/mL in BM. The percentages of CSF/plasma and BM/plasma were 0.74% and 70.37%, respectively. While no direct correlation was observed between CSF and plasma venetoclax levels, there was a trend toward an improved CSF/plasma percentage over time following the last administration of venetoclax. In contrast, a strong correlation was found between BM and plasma levels. This study demonstrated that venetoclax could reach its effective concentration in most patients, suggesting its potential clinical utility in the management of CNS involvement in acute leukemia.

Abstract In the last four decades, the Jiangsu province, like the rest of China, has undergone rapid economic development coupled with a rapid increase in environmental pollution. Freshwater ecosystems have been particularly affected. In Lake Tai, China's third‐largest freshwater lake by volume, water quality has been severely reduced. There is a renewed interest in establishing riparian buffer strips in China as a conservation practice for mitigating agricultural non‐point source pollution. To study the effect of riparian buffers on phosphorus attenuation, eight 50 m × 20 m plots were established between a rice farm and the shore of Lake Tai in China, with the 20 m width facing the lake shore. They were planted with hybrid poplar (Populus deltoides × euramericana), hybrid cypress (Taxodium ascendens × mucronatum), or a mixture of both at densities of 2 m × 3 m, 2 m × 5 m, or 5 m × 5 m, while one plot was left as a control. Samples collected from soil, tree leaves, and groundwater during 2014–2018 were analyzed for multiple forms of phosphorus. Results indicated that riparian buffer width and time (year) were the most significant factors of phosphorus attenuation on all plots. Tree density had a minor effect, with medium density being the most effective, and we found negligible differences among hybrid tree species on attenuating phosphorus. Farmers should use densely vegetated buffer strips at least 15 m wide to ensure a significant reduction in nutrient runoff. Species selection should be based on market value and ecological benefits.

IntroductionSurfactant Protein C gene (SFTPC) is a marker gene of alveolar type 2 cells (AT2), which are the key structures of alveoli. Mutations or deletions in SFTPC cause idiopathic pulmonary fibrosis (IPF). Importantly, IPF is an independent risk factor for non-small cell lung cancer (NSCLC). It suggests that abnormal expression of SFTPC may be relevant to development of NSCLC. However, the function and mechanism of SFTPC in NSCLC are still poor understood until now.MethodsThe expression of SFTPC and the relationship between SFTPC and prognosis of NSCLC were analyzed in TCGA database and our collected clinical NSCLC tissues. Subsequently, the function and mechanism of SFTPC in NSCLC were explored by RNA-sequence, qRT-PCR, Western blot, Immunohistochemical, Wound-healing, Millicell, Transwell assays and mouse tumor xenograft model.ResultsSFTPC was dramatically downregulated in NSCLC tissues from TCGA database and 40 out of 46 collected clinical LUAD tissues compared with adjacent non-tumor tissues. Low expression of SFTPC was associated with poor prognosis of LUAD by TCGA database. Importantly, we confirmed that overexpression of SFTPC significantly inhibited Epithelial-to-Mesenchymal Transition (EMT) process of NSCLC cells by upregulating SOX7 and then inactivating WNT/β-catenin pathway in vitro and in vivo. Particularly, we discovered that low expression of SFTPC was associated with EMT process and low expression of SOX7 in NSCLC tissues.ConclusionOur study revealed a novel mechanism of SFTPC in NSCLC development. Meanwhile, it also might provide a new clue for exploring the molecular mechanism about NSCLC development in patients with IPF in the future.

DNA hydrogels are three-dimensional polymer networks constructed using DNA as the structural building block. Due to the tight binding between hydrophilic groups on DNA chains and water molecules, they exhibit outstanding plasticity and fluid thermodynamic properties, making them one of the best choices for mimicking natural biological tissues. By controlling the backbone building blocks, gelation conditions, and cross-linking methods of DNA hydrogels, hydrogels with different mechanical strengths can be obtained, thus expanding their applications in the field of biology. This review first introduces the relationship between the mechanical properties of DNA hydrogels and their structure, elucidates the approaches and strategies for mechanical property modulation, and focuses on the scheme of controllable design to modulate the mechanical properties of DNA hydrogels for applications in biosensing, cellular function regulation, and bone tissue engineering. Furthermore, this review outlines the future development directions and challenges faced in the mechanical property modulation of DNA hydrogels, providing useful information for the precise design of DNA hydrogels for biological research.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a highly invasive pulmonary malignancy with an extremely poor prognosis. The results of previous studies suggest that ubiquitin-specific peptidase 9X (USP9X) contributes to the progression of numerous types of cancer. Nevertheless, there is little knowledge about the molecular mechanisms and functions of USP9X in the metastasis of PSC. Methods: Immunohistochemistry and western blotting were used to detect USP9X expression levels in PSC tissues and cells. Wound healing, transwell, enzyme-linked immunosorbent assay (ELISA), tube formation, and aortic ring assays were used to examine the function and mechanism of USP9X in the metastasis of PSC. Results: Expression of USP9X was markedly decreased and significantly correlated with metastasis and prognosis of patients with PSC. Then we revealed that USP9X protein levels were negatively associated with the levels of epithelial-mesenchymal transition (EMT) markers and the migration of PSC cells. It was confirmed that USP9X in PSC cells reduced VEGF secretion and inhibited tubule formation of human umbilical vein endothelial cells (HUVEC) in vitro. USP9X was detected to downregulate MMP9. Meanwhile, MMP9 was positively related to EMT, angiogenesis and was negatively related to immune infiltration in the public databases. USP9X was significantly negatively associated with the expression of MMP9, EMT markers, CD31, and positively associated with CD4, and CD8 in PSC tissues. Conclusion: The present study reveals the vital role of USP9X in regulating EMT, angiogenesis and immune infiltration and inhibiting metastasis of PSC via downregulating MMP9, which provides a new effective therapeutic target for PSC.

Background: Post-cardiac arrest brain injury (PCABI) is the leading cause of death in survivors of cardiac arrest (CA). Carbon monoxide-releasing molecule (CORM-3) is a water-soluble exogenous carbon monoxide that has been shown to have neuroprotection benefits in several neurological disease models. However, the effects of CORM-3 on PCABI is still unclear. Methods: A mice model combined asystole with hemorrhage was used. Mice were anesthetized and randomized into 4 groups (n = 12/group) and underwent either 9.5 min CA followed by cardiopulmonary resuscitation (CPR) or sham surgery. CORM-3 (30 mg/kg) or vehicle (normal saline) were administered at 1 h after return of spontaneous circulation or sham surgery. Survival, neurologic deficits, alterations in the permeability of the brain-blood barrier and cerebral blood flow, changes of oxidative stress level, level of neuroinflammation and neuronal degeneration, and the activation of Nrf2/HO-1 signaling pathway were measured. Results: In CORM-3 treated mice that underwent CA/CPR, significantly improved survival (75.00% vs. 58.33%, P = 0.0146 (24 h) and 66.67% vs. 16.67%, P