Search

Abstract The numerous grainboundaries solid electrolyte interface, whether naturally occurring or artificially designed, leads to non-uniform Li metal deposition and consequently results in poor full-battery performance. Herein, a lithium-ion selective transport layer is reported to achieve a highly efficient and dendrite-free lithium metal anode. The layer-by-layer assembled protonated carbon nitride nanosheets present uniform macroscopical structure without grainboundaries. The carbon nitride with ordered pores in basal plane provides high-speed lithium-ion transport channels with low tortuosity. Consequently, the assembled 324 Wh kg−1 pouch cell exhibits 300 stable cycles with a capacity retention of 90.0% and an average Coulombic efficiency up to 99.7%. The ultra-dense Li metal anode makes current collector-free anode possible, achieving high energy density and long cycle life of a 7 Ah cell (506 Wh kg−1, 160 cycles). Thus, it is proved that a macroscopically uniform interface layer with lithium-ion conductive channels could achieve Li metal battery with promising application potential.

Hordeum pusillum (Hordeum pusillum Nutt., 1818) is an annual barley that is native to the west of the North America and widespread in southern United States and tropical America. In this study, we have provided the first complete characterization of the chloroplast genome of H. pusillum. Our research revealed that the circular chloroplast genome of H. pusillum consists of a large single-copy region (LSC: 80,853 bp), a small single-copy region (SSC: 12,745 bp), and a pair of inverted repeat regions (IRs: 21,587 bp), totaling 136,772 bp in length. Within the chloroplast genome of H. pusillum, 91 protein-coding genes, 38 tRNA genes, and ten rRNA genes were identified. To determine the evolutionary relationship of Hordeum species with reported chloroplast genome sequences, we constructed a phylogenetic tree using the entire chloroplast genome sequences. The evolutionary position of H. pusillum corresponds to its geographical location. The chloroplast genome of H. pusillum provided in this study may have significant implications for the phylogenetic study of Poaceae species.

Abstract Brittleness is an important mechanical property of rock. Accurately evaluating rock brittleness and its influence on the TBM tunnelling performance is necessary. In this work, via two practical engineering cases, with the aim of overcoming the difficulty of penetrating extremely hard rock (breccia fused tuff) in the $$Z{\text{huxi}}$$ Z huxi project, the influence of rock brittleness on the TBM tunnelling performance was studied via comparative analysis with that $$Nabang$$ Nabang project. Seven commonly used rock brittleness indices based on stress‒strain curves were summarized, and a brittleness evaluation method suitable for extremely hard rock was determined by introducing the normalized specific energy to obtain brittleness indices for two lithologies (breccia fused tuff and biotite hornblende plagioclase gneiss) in two projects. The influences of rock brittleness on penetration and the specific energy were compared and analysed. The results showed that the brittleness indices $$B3$$ B 3 and $$B5$$ B 5 were more suitable for evaluating rock brittleness. Rock brittleness influenced the TBM tunnelling performance, but this influence gradually decreased with decreasing uniaxial compressive strength ( $$UCS$$ UCS ), which is obviously less than that of the rock strength. When the $$UCS$$ UCS was lower than 150 MPa, the TBM tunnelling parameters could be adjusted within a significant margin to eliminate the influence of rock brittleness, which could be ignored when predicting the tunnelling performance. When the $$UCS$$ UCS was greater than 150 MPa, rock brittleness imposed a notable influence on the tunnelling performance, which must be considered when predicting the tunnelling performance. This research could provide reference data for evaluating the hard rock brittleness index and accurately predicting the TBM tunnelling performance in engineering practice.

Abiotic and biotic stressors adversely affect plant survival, biomass generation, and crop yields. As the global availability of arable land declines and the impacts of global warming intensify, such stressors may have increasingly pronounced effects on agricultural productivity. Currently, researchers face the overarching challenge of comprehensively enhancing plant resilience to abiotic and biotic stressors. The secondary cell wall plays a crucial role in bolstering the stress resistance of plants. To increase plant resistance to stress through genetic manipulation of the secondary cell wall, we cloned a cell wall protein designated glycine-rich protein-like (GhGRPL) from cotton fibers, and found that it is specifically expressed during the period of secondary cell wall biosynthesis. Notably, this protein differs from its Arabidopsis homolog, AtGRP, since its glycine-rich domain is deficient in glycine residues. GhGRPL is involved in secondary cell wall deposition. Upregulation of GhGRPL enhances lignin accumulation and, consequently, the thickness of the secondary cell walls, thereby increasing the plant's resistance to abiotic stressors, such as drought and salinity, and biotic threats, including Verticillium dahliae infection. Conversely, interference with GhGRPL expression in cotton reduces lignin accumulation and compromises that resistance. Taken together, our findings elucidate the role of GhGRPL in regulating secondary cell wall development through its influence on lignin deposition, which, in turn, reinforces cell wall robustness and impermeability. These findings highlight the promising near-future prospect of adopting GhGRPL as a viable, effective approach for enhancing plant resilience to abiotic and biotic stress factors.

Abstract Background Omadacycline is a new generation of tetracycline antibiotics, and its clinical application is increasing. We report the first case of acute pancreatitis possibly induced by omadacycline. Case presentation The patient was admitted to the emergency intensive care unit due to community-acquired pneumonia. The initial treatment consisted of meropenem combined with levofloxacin, and the regimen was subsequently switched to omadacycline combined with cefoperazone/sulbactam due to sputum culture showing carbapenem-resistant Acinetobacter baumannii. Seven days after the administration of omadacycline, abdominal tenderness occurred, and CT scan revealed an enlarged gallbladder with exudation from the pancreatic head. The patient was diagnosed with acute pancreatitis and improved after dis-continuing omadacycline. Conclusions Omadacycline, like other tetracycline antibiotics, may cause pancreatitis. Combination medications can be an important factor in this adverse reaction.

Abstract Objective To investigate changes in proportions of peripheral blood lymphocyte subsets, the correlation between the lymphocyte subsets and cytokine levels in patients with GluR3B antibody-positive epilepsy, analyze the role of GluR3B antibodies and cytokines in the progression of epilepsy. In addition, the immunotherapeutic effect in patients with GluR3B antibody-positive epilepsy will be evaluated. Methods Patients with epilepsy hospitalized in the Department of Neurology of the affiliated Hospital of Xuzhou Medical University from December 2016 to May 2023 were recruited. GluR3B antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). Lymphocyte subset proportions were determined using flow cytometry, and serum concentrations of 12 cytokines were measured using cytometric beads array. Differences in T lymphocyte subsets and inflammatory factors were analysed between GluR3B antibody positive and negative patients. Structural equation modeling (SEM) was used to analyse the role of GluR3B antibodies and inflammatory factors in drug-resistant epilepsy (DRE). Finally, the therapeutic effect of immunotherapy on epilepsy patients with GluR3B antibodies was assessed. Results In this study, sixty-four cases of DRE, sixty-six cases of drug-naïve epilepsy (DNE), and forty-one cases of drug-responsive epilepsy were recruited. (1) DRE patients with positive GluR3B antibody were characterized by a significant increase in the proportion of cluster of differentiation (CD)4+ T lymphocytes, a decrease in CD8+ T lymphocytes, and an increase of CD4+/CD8+ ratio. Similar alterations in T lymphocyte subsets were observed in GluR3B antibody-positive patients with DNE. GluR3B antibody levels correlated positively with CD4+ T lymphocytes (r = 0.23) and negatively with CD8+ T lymphocytes (r=-0.18). (2) In patients with DRE, the serum concentrations of interleukin-1β (IL-1β), IL-8, and interferon-gamma (IFN-γ) were significantly higher in those with positive GluR3B antibody compared to those with negative GluR3B antibody. Serum IL-1β levels were also higher in GluR3B antibody-positive DNE patients compared to antibody-negative DNE patients. In drug-responsive epilepsy patients with GluR3B antibody-positive, both serum IL-1β and IFN-γ levels were higher than those with GluR3B antibody-negative. Moreover, the concentrations of serum GluR3B antibody were positively correlated with the levels of IL-1β, IL-8, and IFN-γ. (3) SEM analysis indicated that GluR3B antibody may be a direct risk factor for DRE (direct effect = 4.479, 95%CI 0.409–8.503), or may be involved in DRE progression through affecting IFN-γ and IL-8 levels (total indirect effect = 5.101, 95%CI 1.756–8.818). (4) Immunotherapy significantly decreased seizure frequency and serum GluR3B antibody levels, and the seizure frequency was positively correlated with the levels of GluR3B antibody levels in patients receiving immunotherapy. Conclusions This study demonstrates that GluR3B antibody may influence the progression of epilepsy through altering the proportion of CD4+ and CD8+ lymphocyte subsets and increasing proinflammatory cytokines. The seizure suppression of immunotherapy is associated with the decrease of GluR3B antibody levels. Thus, the present study contributes to a better understanding of the immunoregulatory mechanisms of autoimmune-associated epilepsy and provides a potential target for DRE.

Abstract Background Postoperative refracture of osteoporotic compression fractures in the elderly due to underlying illnesses is a complicated matter involving several variables. A multidisciplinary approach involving orthopedics, geriatrics, endocrinology, and rehabilitation medicine is necessary for an investigation of these issues. investigating the impact of older patients’ underlying medical conditions on the refracture of osteoporotic compression fractures following surgery. Methods A retrospective analysis was conducted on 2383 patients between August 2013 and August 2023. 550 patients with comorbid geriatric underlying diseases were screened, 183 patients underwent refractories, and 367 patients were classified as non-refractories. The patients were then divided into two groups: those undergoing refractories and those not, and the underlying diseases of the patients in both groups were examined using ROC curves and unifactorial and multifactorial logistic regression analyses. Results Among the patients gathered, the frequency of re-fracture was 33.3%. A statistically significant difference was observed when re-fracture was linked to patients with long-term alcohol consumption, operated vertebrae ≤ 1, hypertension, COPD, diabetes mellitus, stroke sequelae, conservative treatment of coronary heart disease, trauma, mental abnormality, scoliosis, and chronic renal disease. Having hypertension decreased the risk of re-fracture (P = 0.018, OR = 0.548), while alcohol intake ≥ 10years (P = 0.003, OR = 2.165), mental abnormality (P

Abstract Background Kagami–Ogata syndrome (KOS) and Temple syndrome (TS) are two imprinting disorders characterized by the absence or reduced expression of maternal or paternal genes in the chromosome 14q32 region, respectively. We present a rare prenatally diagnosed case of recurrent KOS inherited from a mother affected by TS. Case presentation The woman’s two affected pregnancies exhibited recurrent manifestations of prenatal overgrowth, polyhydramnios, and omphalocele, as well as a small bell-shaped thorax with coat-hanger ribs postnatally. Prenatal genetic testing using a single-nucleotide polymorphism array detected a 268.2-kb deletion in the chromosome 14q32 imprinted region inherited from the mother, leading to the diagnosis of KOS. Additionally, the woman carried a de novo deletion in the paternal chromosome 14q32 imprinted region and presented with short stature and small hands and feet, indicating a diagnosis of TS. Conclusions Given the rarity of KOS as an imprinting disorder, accurate prenatal diagnosis of this rare imprinting disorder depends on two factors: (1) increasing clinician recognition of the clinical phenotype and related genetic mechanism, and (2) emphasizing the importance of imprinted regions in the CMA workflow for laboratory analysis.

Objective: Australia has relatively high multiple myeloma (MM) incidence and mortality rates. Advancements in MM treatment over recent decades have driven improvements in MM survival in high-income countries; however, reporting in Australia is limited. We investigated temporal trends in population-wide MM survival across 3 periods of treatment advancements in New South Wales (NSW), Australia. Methods: Individuals with an MM diagnosis in the NSW Cancer Registry between 1985 and 2015 with vital follow-up to 2020, were categorized into 3 previously defined treatment eras according to their diagnosis date (1985–1995, chemotherapy only; 1996–2007, autologous stem cell transplantation; and 2008–2015, novel agents including proteasome inhibitors and immunomodulatory drugs). Both relative survival and cause-specific survival according to Fine and Gray’s competing risks cumulative incidence function were calculated by treatment era and age at diagnosis. Results: Overall, 11,591 individuals were included in the study, with a median age of 70 years at diagnosis. Five-year relative survival improved over the 36-year (1985–2020) study period (31.0% in 1985–1995; 41.9% in 1996–2007; and 56.1% in 2008–2015). For individuals diagnosed before 70 years of age, the 5-year relative survival nearly doubled, from 36.5% in 1985–1995 to 68.5% in 2008–2015. Improvements for those > 70 years of age were less pronounced between 1985–1995 and 1996–2007; however, significant improvements were observed for those diagnosed in 2008–2015. Similar overall and age-specific patterns were observed for cause-specific survival. After adjustment for gender and age at diagnosis, treatment era was strongly associated with both relative and cause-specific survival (P < 0.0001). Conclusions: Survival of individuals with MM is improving in Australia with treatment advances. However, older age groups continue to experience poor survival outcomes with only modest improvements over time. Given the increasing prevalence of MM in Australia, the effects of MM treatment on quality of life, particularly in older age, warrant further attention.

Strength and electrical conductivity (EC) are key properties for heat-resistant Al-Zr-based alloy wires used as overhead transmission lines. Developing high-strength conductors with EC over 61.0% IACS has been a long-standing issue for heat-resistant Al conductive wires. In this work, a new design idea involving the coupling design of deformation and ageing was innovatively proposed to produce ultra-heat-resistant Al-0.2Zr-0.06Sc wires. The desired combination of high strength (195 ± 2 MPa) and good EC (61.2% IACS) was successfully achieved without annealing treatment. The strength residual rate of cold-drawn Al-0.2Zr-0.06Sc wire is as high as 94.0% after heat exposure of 280°C/1 h.

Introduction China is the largest tobacco consumer in the world, and tobacco poses a serious threat to the health of pregnant women. However, there are relatively few domestic studies on smoking during pregnancy and childbirth outcomes among pregnant women. The purpose of this study was to analyze the effect of active and passive smoking on pregnant women and their pregnancy outcomes, providing evidence and recommendations for intervention measures. Methods This was a cohort study in Shanghai from April 2021 to September 2023. According to the smoking status of pregnant women, they were divided into three groups: active smokers, passive smokers and non-smokers. A self-designed questionnaire was utilized to conduct the survey, and their pregnancy outcomes were tracked and followed up. Results A total of 3446 pregnant women were included in this study, among which 2.1% were active smokers, 43.5% were passive smokers, and 54.4% were nonsmokers. The average age of the pregnant women was 29.9 years, and 41.2% had a university degree or higher. The education level of active smokers and passive smokers was significantly lower than that of non-smokers (p

Abstract Objective The aim of this study was to assess the association of neutrophil lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and system inflammation response index (SIRI) with the all-cause mortality and diabetes-cardiovascular mortality in participants with diabetic retinopathy (DR). Methods A total of 572 participants with DR from NHANES were included, and divided into survival group (n = 440) and all-cause death group (n = 132). NLR = neutrophil count/lymphocyte count, MLR = monocyte count/lymphocyte count, SIRI = (neutrophil count × monocyte count)/lymphocyte count. We utilized the NHANES Public-Use Linked Mortality File through April 26, 2022, to determine mortality status. Diabetes-cardiovascular death was defined as death resulting from heart disease, cerebrovascular disease, or diabetes mellitus. The Spearson Correlation Analysis, Kaplan-Meier curves, Cox proportional hazards regression models, Restricted cubic spline plots and Decision Curve Analysis were used. Results The all-cause mortality and diabetes-cardiovascular mortality were significantly higher in NLR ≥ 1.516, MLR ≥ 0.309, SIRI ≥ 0.756, and NLR + MLR + SIRI subgroups than NLR 60 years participants, the all-cause mortality and diabetes-cardiovascular mortality were significantly higher in NLR ≥ 1.516, MLR ≥ 0.309, SIRI ≥ 0.756, and NLR + MLR + SIRI subgroups than NLR

The effect of varying rare earth element cerium (Ce) contents (0∼0.0792 wt%) on the austenite grain size of ultra-high-strength engineering steel has been studied under different austenitization conditions (holding time of 5∼360 min at temperatures ranging from 900 °C to 1200 °C). Results show that the addition of Ce can refine grains, and the refining effect becomes more pronounced as the Ce content increases. The inhibition of austenite grain growth by fine Ce-containing inclusions during the holding process has been observed through laser scanning confocal microscopy (LSCM) and field-emission scanning electron microscope (FE-SEM) equipped with an energy dispersive spectrometer (EDS), and the pinning effect of Ce-containing inclusions on the austenite grain boundaries is the primary factor for the refinement of austenite grains. Besides, theoretical calculations have shown that the lattice misfits between the (100) plane of CeP and the (111) plane of the γ-phase is 7.83%, indicating that CeP could serve as a heterogeneous nucleation core for the γ-phase and was moderately effective. Furthermore, the uniformization effect of Ce on the grains is more prominent than the refining effect at the holding temperatures of 1000 °C and 1200 °C.

Abstract Background This study aimed to investigate the effects of immune checkpoint inhibitors (ICIs) versus chemotherapy on the prognosis of real‐world diffuse pleural mesothelioma patients in China. Methods Clinical data of 90 patients with diffuse pleural mesothelioma from 2019 to 2022 were collected from Harbin Medical University Cancer Hospital. Patients were divided into two groups: the ICIs‐treated group (n = 46) and the chemotherapy‐only group (n = 44). The efficacy and safety of immunotherapy relative to chemotherapy at different treatment stages were explored. Results The median progression‐free survival (PFS) was 10.0 and 7.0 months, and the median overall survival (OS) was 24.7 and 15.8 months in the ICIs‐treated group and the chemotherapy group, respectively. The ICIs‐treated group showed an 11% increase in objective response rate (ORR) (52.2% vs. 41.0%) and an 8.0% increase in disease control rate (DCR) (78.3% vs. 70.0%) compared to the chemotherapy group. The Kaplan–Meier curves demonstrated significant PFS (HR: 0.61; 95% CI: 0.38–0.98; p = 0.038) and OS (HR: 0.47; 95% CI: 0.26–0.86; p = 0.011) benefits of receiving immunotherapy over chemotherapy alone. Subgroup analysis according to treatment timing showed the same trend. Conclusion In patients with nonsurgical diffuse pleural mesothelioma, immunotherapy achieved better survival benefits compared to chemotherapy in both first‐ and second‐/third‐line treatments. The early addition of immunotherapy improved survival in patients with nonsurgical diffuse pleural mesothelioma.

Abstract Background There is a scarcity of prospective clinical research evidence regarding the utilization of transvaginal natural orifice translumenal endoscopic surgery (vNOTES) as a treatment option for ovarian cysts. The objective of this study was to assess the feasibility and safety of employing vNOTES for the management of ovarian cysts. Methods Our study included women between the ages of 18 and 70 who intended to undergo surgical intervention for benign lesions. Stratified blocked randomization was employed to allocate participants into groups. The main objective was to assess whether the assigned group adhered to the recommended surgical technique for ovarian cystectomy or adnexectomy, without any deviation to alternative surgical methods. Results A total of 196 patients were included in the study, with all surgeries in each group being conducted according to the assigned procedures. Among them, the ovarian cystectomy layer included 58 cases in the vNOTES group and 58 cases in the conventional laparoscopy (CL) groups. The adnexectomy layer included 40 cases in the vNOTES group and 40 cases in the CL group. Utilizing a sensitivity analysis, the two-sided 95% lower confidence limit was determined to be 5.5% for the disparity in proportions between the vNOTES groups and CL groups. These lower limits fell below the predetermined non-inferiority margin of 10%. Conclusions The study findings demonstrate that vNOTES was not inferior to CL in terms of adnexectomy or ovarian cystectomy. vNOTES can be considered a more minimally invasive surgical approach, as it results in reduced postoperative pain, faster recovery, and absence of visible incisions. Overall, vNOTES proves to be a safe, feasible, and less invasive treatment option. Trial registration This study retrospectively registered with the China Clinical Trial Registry with the registration number ChiCTR2100052223(22-10-2021).

Abstract This research focuses on the design of heat dissipation system for lithium-ion battery packs of electric vehicles, and adopts artificial intelligence optimization algorithm to improve the heat dissipation efficiency of the system. By integrating genetic algorithms and particle swarm optimization, the research goal is to optimize key design parameters of the cooling system to improve temperature control and extend battery life. In the process of algorithm implementation, genetic algorithm improves the diversity of population through crossover and mutation operations, thus enhancing the global search ability. Particle swarm optimization (PSO) improves local search accuracy and convergence speed by dynamically adjusting inertia weight and learning factor. The effects of different design schemes on heat dissipation performance were systematically evaluated by using computational fluid dynamics (CFD) software. The experimental results show that the efficiency of the cooling system is significantly improved after the application of the optimization algorithm, especially in the aspects of temperature distribution uniformity and maximum temperature reduction. The optimization algorithm also successfully shortens the thermal response time of the system and improves the adaptability and stability of the system under different working conditions. The computational complexity and execution time of these algorithms are also analyzed, which proves the efficiency and feasibility of these algorithms in practical applications. This study demonstrates the practicability and effectiveness of artificial intelligence optimization algorithm in the design of heat dissipation system of lithium-ion battery pack for electric vehicles, and provides valuable reference and practical guidance for the progress of heat dissipation technology of electric vehicles in the future.

Abstract Background Streptococcus mutans (S. mutans) is an important pathogenic bacterium that causes dental caries, while Streptococcus gordonii (S. gordonii) is a non-cariogenic bacterium that inhibits the growth of S. mutans. The SepM protein can promote the inhibitory ability of S. mutans against S. gordonii by cleaving CSP-21 and activating the ComDE two-component system. This study was designed to explore sepM mutation in S. mutans clinical isolates and related function in the regulation of interactions with S. gordonii. Methods The S. mutans clinical strains that can inhibit the growth of S. gordonii constitute the inhibitory group. 286 C-serotype S. mutans strains were categorized into S. gordonii inhibitory (n = 114) and non-inhibitory bacteria (n = 172). We detected sanger sequencing of sepM gene, the expression levels of related genes and proteins in clinical isolates, obtained prokaryotic expression and purification of mutated proteins, and analyzed the effect of the target mutations on the binding between SepM and CSP-21. Results We found that C482T, G533A, and G661A missense mutations were presented at significantly higher frequency in the inhibitory group relative to the non-inhibitory group. There was no significant difference in the expression of the sepM gene between selected clinical isolates harboring the G533A mutation and the control group. The expression levels of SepM, phosphorylated ComD, and ComE in the mutation group were significantly higher than those in the control group. SepM_control and SepM_D221N (G661A at the gene level) were found to contain two residues close to the active center while SepM_G178D (G533A at the gene level) contained three residues close to the active center. At 25 °C and a pH of 5.5, SepM_D221N (G661A) exhibited higher affinity for CSP-21 (KD = 8.25 µM) than did the SepM control (KD = 33.1 µM), and at 25 °C and a pH of 7.5, SepM_G178D (G533A) exhibited higher affinity (KD = 3.02 µM) than the SepM control (KD = 15.9 µM). It means that it is pH dependent. Conclusions Our data suggest that increased cleavage of CSP-21 by the the mutant SepM may be a reason for the higher inhibitory effect of S. mutans on S. gordonii .

Abstract Background Oritavancin is a new generation of semi-synthetic glycopeptide antibiotics against Gram-positive bacteria, which served as the first and only antibiotic with a single-dose therapeutic regimen to treat ABSSSI. A naturally occurring glycopeptide A82846B is the direct precursor of oritavancin. However, its application has been hampered by low yields and homologous impurities. This study established a multi-step combinatorial strategy to rationally construct a high-quality and high-efficiency biosynthesis system for A82846B and systematically optimize its fermentation process to break through the bottleneck of microbial fermentation production. Results Firstly, based on the genome sequencing and analysis, we deleted putative competitive pathways and constructed a better A82846B-producing strain with a cleaner metabolic background, increasing A82846B production from 92 to 174 mg/L. Subsequently, the PhiC31 integrase system was introduced based on the CRISPR-Cas12a system. Then, the fermentation level of A82846B was improved to 226 mg/L by over-expressing the pathway-specific regulator StrR via the constructed PhiC31 system. Furthermore, overexpressing glycosyl-synthesis gene evaE enhanced the production to 332 mg/L due to the great conversion of the intermediate to target product. Finally, the scale-up production of A82846B reached 725 mg/L in a 15 L fermenter under fermentation optimization, which is the highest reported yield of A82846B without the generation of homologous impurities. Conclusion Under approaches including blocking competitive pathways, inserting site-specific recombination system, overexpressing regulator, overexpressing glycosyl-synthesis gene and optimizing fermentation process, a multi-step combinatorial strategy for the high-level production of A82846B was developed, constructing a high-producing strain AO-6. The combinatorial strategies employed here can be widely applied to improve the fermentation level of other microbial secondary metabolites, providing a reference for constructing an efficient microbial cell factory for high-value natural products.

Abstract Background Papillary thyroid carcinoma (PTC) is globally prevalent and associated with an increased risk of lymph node metastasis (LNM). The role of cancer-associated fibroblasts (CAFs) in PTC remains unclear. Methods We collected postoperative pathological hematoxylin–eosin (HE) slides from 984 included patients with PTC to analyze the density of CAF infiltration at the invasive front of the tumor using QuPath software. The relationship between CAF density and LNM was assessed. Single-cell RNA sequencing (scRNA-seq) data from GSE193581 and GSE184362 datasets were integrated to analyze CAF infiltration in PTC. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of CD36+CAF in two PTC cell lines, TPC1 and K1. Results A significant correlation was observed between high fibrosis density at the invasive front of the tumor and LNM. Analysis of scRNA-seq data revealed metastasis-associated myoCAFs with robust intercellular interactions. A diagnostic model based on metastasis-associated myoCAF genes was established and refined through deep learning methods. CD36 positive expression in CAFs can significantly promote the proliferation, migration, and invasion abilities of PTC cells, while inhibiting the apoptosis of PTC cells. Conclusion This study addresses the significant issue of LNM risk in PTC. Analysis of postoperative HE pathological slides from a substantial patient cohort reveals a notable association between high fibrosis density at the invasive front of the tumor and LNM. Integration of scRNA-seq data comprehensively analyzes CAF infiltration in PTC, identifying metastasis-associated myoCAFs with strong intercellular interactions. In vitro experimental results indicate that CD36 positive expression in CAFs plays a promoting role in the progression of PTC. Overall, these findings provide crucial insights into the function of CAF subset in PTC metastasis.

Abstract Background Job crafting is defined as a series of proactive behaviors exhibited by employees in order to balance work resources and needs, which has a significant positive impact on the nurses. It is necessary to find the core factors that influence the job crafting, as emergency nurses deal with the most complex tasks, so as to improve their job satisfaction. Objectives To investigate the core factors of job crafting among emergency nurses. Methods A cross-sectional design was used in the study. A total of 255 nurses were recruited from two hospitals in Zhengzhou and Shenzhen, China in December 2021. 255 nurses completed an online questionnaire. Hierarchical regression models and fsQCA models were used to explore the factors influencing job crafting among emergency nurses and helped us to identify core factors. Results The hierarchical regression model and the fsQCA model found that the occupational benefit, psychological empowerment, and research experience were the core factors affecting their job crafting. Job involvement was not significant in the regression model, but the QCA model indicated that it needs to be combined with other factors to impact on job crafting. The QCA model uncovered seven key conditional configurations that led to high and low job crafting among emergency nurses, explaining 80.0% of the results for high job crafting and 82.6% of the results for the low job crafting, respectively. Conclusions The results of this study provide valuable insights into the job crafting experienced by emergency nurses. Junior emergency nurses should be granted a high level of psychological empowerment without assigning them overly complex tasks, such as research tasks, as these challenges can stop their job crafting. Intermediate and senior emergency nurses, on the other hand, can be assigned research tasks coupled with high psychological empowerment to enhance their job crafting.

Abstract Both irradiation and dislocations have been proposed as routes to rationally manipulate spatial distribution and micromorphology of precipitate. An interesting effect emerges in Fe–10at.%Cu–3at.%Mn–1.5at.%Ni–1.5at.%Al alloy due to the synergistic-competitive roles of dislocation loop and irradiation. Base on cascade mixing, vacancy-interstitial atoms and dislocation stress field model, we examine nucleation and growth dynamics of Cu-rich precipitates, where both dislocation loop and irradiation act in conjunction. Analytical treatments identify regimes, where the distribution of elements and point defects due to irradiation and dislocations are specific to the Cu-rich precipitates. Simulation results reveal that density, size and distribution of Cu-rich precipitates are a manifestation of the competing effects of the dislocation loop and the irradiation rate. More specifically, the dislocation loop preferentially assists the formation of precipitates and new dislocations at lower irradiation rates. Only the irradiation induces the formation of Cu-rich precipitates with the irradiation rate continues to increase. Equipped with molecular dynamics, where reproduces major interaction features of the solutes with point defects under displacement cascade, can verify multi-component morphologies of Cu-rich precipitates. This modeling framework provides an avenue to explore the role of dislocation loop and irradiation on the microstructural evolution of Cu-rich precipitates.

BackgroundWith the acceleration of population aging, depressive symptoms in older adults have become an urgent global public health issue. It is critical to understand how to prevent and intervene the epidemic of depressive symptoms. Several studies have reported the prevalence of depressive symptoms among older adults in urban and rural China, but there is a lack of cross-sectional studies on the prevalence of depressive symptoms among older adults in Anhui Province after the COVID-19 pandemic.MethodsBetween December 2023 and February 2024, we used convenience sampling to randomly recruit 1,175 older people over 60 years old in Anhui Province, China. The PHQ-9 depressive symptom scale, frailty scale, and social frailty scale were used in the study. Logistic regression was used to analyze the association between frailty, social frailty, family health and depressive symptoms in older adults.ResultOf the 1,175 participants, 406 (34.6%) had depressive symptoms. Binary logistic regression results showed that Status of body pain (p

Abstract The development of environmentally adaptive solutions for magnetically actuated microrobots to enable targeted delivery in complex and confined fluid environments presents a significant challenge. Inspired by the natural locomotion of crucian carp, a barbell‐shaped soft microrobot (MBS2M) is proposed. A mechano‐electromagnetic hybrid actuation system is developed to generate oscillating magnetic fields to manipulate the microrobot. The MBS2M can seamlessly transition between three fundamental locomotion modes: fast navigation (FN), high‐precision navigation (HPN), and fixed‐point rotation (FPR). Moreover, the MBS2M can move in reverse without turning. The multimodal locomotion endows the MBS2M's adaptability in diverse environments. It can smoothly pass through confined channels, climb over obstacles, overcome gravity for vertical motion, track complex pathways, traverse viscous environments, overcome low fluid resistance, and navigate complex spaces mimicking in vivo environments. Additionally, the MBS2M is capable of drug loading and release in response to ultrasound excitation. In an ex vivo porcine liver vein, the microrobot demonstrated targeted navigation under ultrasound guidance, showcasing its potential for specialized in vivo tasks.

PurposeTo explore the role of deep learning (DL) and radiomics-based integrated approach based on contrast enhanced magnetic resonance imaging (CEMRI) for predicting early recurrence (ER) in hepatocellular carcinoma (HCC) patients after curative resection.MethodsTotal 165 HCC patients (ER, n = 96 vs. non-early recurrence (NER), n = 69) were retrospectively collected and divided into a training cohort (n = 132) and a validation cohort (n = 33). From pretreatment CEMR images, a total of 3111 radiomics features were extracted, and radiomics models were constructed using five machine learning classifiers (logistic regression, support vector machine, k-nearest neighbor, extreme gradient Boosting, and multilayer perceptron). DL models were established via three variations of ResNet architecture. The clinical-radiological (CR), radiomics combined with clinical-radiological (RCR), and deep learning combined with RCR (DLRCR) models were constructed. Model discrimination, calibration, and clinical utilities were evaluated by receiver operating characteristic curve, calibration curve, and decision curve analysis, respectively. The best-performing model was compared with the widely used staging systems and preoperative prognostic indexes.ResultsThe RCR model (area under the curve (AUC): 0.841 and 0.811) and the optimal radiomics model (AUC: 0.839 and 0.804) achieved better performance than the CR model (AUC: 0.662 and 0.752) in the training and validation cohorts, respectively. The optimal DL model (AUC: 0.870 and 0.826) outperformed the radiomics model in the both cohorts. The DL, radiomics, and CR predictors (aspartate aminotransferase (AST) and tumor diameter) were combined to construct the DLRCR model. The DLRCR model presented the best performance over any model, yielding an AUC, an accuracy, a sensitivity, a specificity of 0.917, 0.886, 0.889, and 0.882 in the training cohort and of 0.844, 0.818, 0.800, and 0.846 in the validation cohort, respectively. The DLRCR model achieved better clinical utility compared to the clinical staging systems and prognostic indexes.ConclusionBoth radiomics and DL models derived from CEMRI can predict HCC recurrence, and DL and radiomics-based integrated approach can provide a more effective tool for the precise prediction of ER for HCC patients undergoing resection.

IntroductionThis study was to analyze the dynamics of tissue damage and inflammatory response markers perioperatively and whether these differ between robotic laparoscopy and conventional laparoscopy in early endometrial cancer.MethodsIn a randomized controlled trial conducted at SHANGHAI FIRST MATERNITY and INFANT HOSPITAL, eighty women with early-stage, low-risk endometrial cancer were randomly assigned to receive either robotic or conventional laparoscopy. Blood samples were collected at admission, immediately before surgery, 2 h after surgery, 24 h after surgery, 48 h after surgery, and 1 week after surgery. The samples were analyzed for various biomarkers associated with inflammatory processes and tissue damage. These included high-sensitivity C-reactive protein (hs-CRP), white blood cell count (WBC), platelet count, interleukin-6 (IL-6), cortisol, creatine kinase (CK), and tumor necrosis factor-alpha (TNF-α). These markers provide insights into the underlying physiological responses and potential tissue-level changes within the study participants.ResultsThere was no significant difference in clinical and preoperative data between two groups. The results showed that the patients who underwent robotic laparoscopy had a longer pre-surgical time compared to the conventional laparoscopy group. However, the robotic group had shorter operating times, quicker vaginal cuff closures, and lower estimated blood loss compared to the conventional laparoscopy group. The hospital stays, Visual Analog Scale (VAS) score and drainage volume on the first day after operation were lower in robotic group compared to conventional laparoscopy group. hs-CRP, WBC, IL-6 and cortisol were significantly lower in the robotic group, though the differences were transient.DiscussionThis study demonstrated that robotic laparoscopy, used in early endometrial cancer treatment, leads to a reduced inflammatory response, less tissue damage, and lower stress levels, as evidenced by decreased levels of hs-CRP, IL-6, and cortisol, compared to conventional laparoscopy. These findings suggest that robot- laparoscopy may facilitate a quicker recovery and improve patient-reported outcomes.

IntroductionTo assess the prevailing trends in the incidence of ischemic heart disease (IHD) across 204 countries and territories from 1990 to 2019, and to elucidate their correlations with age, period, and birth cohort, a comprehensive analysis was conducted.MethodsFrom 1990 to 2019, we employed the Global Burden of Disease Study (GBD) Results Tool in conjunction with an age-period-cohort model. This approach facilitated the estimation of annual percentage changes in incidence, referred to as net drifts, encompassing the overall population. Additionally, we calculated annual percentage changes spanning ages 15 - 19 to 95 + years, denoted as local drifts. Furthermore, our analysis involved determining period and cohort relative risks, elucidating the effects associated with distinct periods and birth cohorts.ResultsGlobally, 21,203,479 [95% uncertainty interval (UI): 18,799,322 − 23,704,124] cases of IHD occurred in 2019. There were 33 countries with at least 100000 cases. Between 1990 and 2019, the net drift of IHD incidence exhibited a range from −1.7% per year [95% confidence interval (CI): −1.79, −1.61] in countries with a high socio-demographic index (SDI) to 0.08% per year (95% CI: 0.05, 0.11) in countries with a low SDI. Age effects across all countries and genders demonstrated an increasing trend over time, indicating age as a significant risk factor for IHD. Moreover, period and cohort effects in higher SDI countries exhibited a more rapid decline in both genders compared to lower SDI countries. The findings indicated that nations with a higher SDI manifested overall favorable trends in the relative risk of IHD incidence, both across time and in successive younger birth cohorts.DiscussionThe incidence of IHD serves as a valuable and accessible indicator for assessing trends in IHD provision, spanning from early youth through later life. Enhancements in IHD prevention have the potential to mitigate risks for successively younger cohorts and, over time, redistribute the risk across all age groups. Despite global declines in IHD incidence over the last three decades, decreasing trends in incidence have slowed and, in some countries, flattened. Many countries have experienced unfavorable period and cohort effects.

Abstract Lung cancer (LC) is the leading cause of cancer‐related mortality worldwide. Radiotherapy is the main component of LC treatment; however, its efficacy is often limited by radioresistance development, resulting in unsatisfactory clinical outcomes. Here, we found that LC radiosensitivity is up‐regulated by decreased expression of long‐chain acyl‐CoA synthase 6 (ACSL6) after irradiation. Deletion of ACSL6 results in significant elevation of Friend leukemia integration 1 transcription factor (FLI1) and a marked decline of collagens (COLs). Blocking of ACSL6 impairs the tumor growth and upregulates FLI1, which reduces the levels of COLs and compromises irradiation‐induced autophagy, leading to considerable therapeutic benefits during radiotherapy. Moreover, the direct interaction between ACSL6 and FLI1 and engagement between FLI1 and COLs indicates the involvement of the ACSL6‐FLI1‐COL axis. Finally, the potently adjusted autophagy flux reduces its otherwise contributive capability in surviving irradiation stress and leads to satisfactory radiosensitization for LC radiotherapy. These results demonstrate that enhanced ACSL6 expression promotes the aggressive performance of irradiated LC through increased FLI1‐COL‐mediated autophagy flux. Thus, the ACSL6‐FLI1‐Col‐autophagy axis may be targeted to enhance the radiosensitivity of LC and improve the management of LC in radiotherapy.

The liver is the largest solid organ in the body and is primarily composed of hepatocytes (HCs), endothelial cells (ECs), Kupffer cells (KCs), and hepatic stellate cells (HSCs), which spatially interact and cooperate with each other to maintain liver homeostasis. However, the complexity and molecular mechanisms underlying the crosstalk between these different cell types remain to be revealed. Here, we generated mice with conditional deletion of Gdf2 (also known as Bmp9) and Bmp10 in different liver cell types and demonstrated that HSCs were the major source of GDF2 and BMP10 in the liver. Using transgenic ALK1 (receptor for GDF2 and BMP10) reporter mice, we found that ALK1 is expressed on KCs and ECs other than HCs and HSCs, and GDF2 and BMP10 secreted by HSCs promote the differentiation of KCs and ECs and maintain their identity. Pdgfb expression was significantly upregulated in KCs and ECs after Gdf2 and Bmp10 deletion, ultimately leading to HSCs activation and liver fibrosis. ECs express several angiocrine factors, such as BMP2, BMP6, Wnt2, and Rspo3, to regulate HC iron metabolism and metabolic zonation. We found that these angiocrine factors were significantly decreased in ECs from Gdf2/Bmp10HSC-KO mice, which further resulted in liver iron overload and disruption of HC zonation. In summary, we demonstrated that HSCs play a central role in mediating liver cell-cell crosstalk via the production of GDF2 and BMP10, highlighting the important role of intercellular interaction in organ development and homeostasis.

IntroductionPhosphoinositide-3-kinase (PI3K) is overexpressed in many tumors and is, thus, an ideal target for cancer treatments. Accordingly, there is an urgent need for the development of PI3K inhibitors with high potency and low toxicity.MethodsIn this study, we designed and synthesized a series of 2,4-dimorpholinopyrimidine-5-carbonitrile derivatives, which were evaluated for their PI3K inhibitory potency.Results and discussionCompound 17p demonstrated comparable PI3Kα inhibitory activity (IC50: 31.8 ± 4.1 nM) to the positive control, BKM-120 (IC50: 44.6 ± 3.6 nM). In addition, 17p showed significant inhibitory activity against PI3Kδ (IC50: 15.4 ± 1.9 nM) and significant isoform selectivity against PI3Kβ, PI3Kγ, and mTOR. Furthermore, 17p exhibited good antiproliferative activities against cancer cell activity and good safety in the Ames and hERG tests while having outstanding liver microsomal stability in vitro, with half-lives of 38.5 min in rats and 127.9 min in humans. In addition, in an apoptosis assay, 17p could induce dose-dependent cytotoxicity in the ovarian cancer cell line A2780. In a pharmacokinetic study, 17p was stable (T½: 2.03 h) and showed high bioavailability (46.2%). Collectively, these results indicate that 17p could be a promising PI3K agent for cancer treatment.

ObjectiveThis study aimed to enhance the understanding of cardio-cerebral infarction (CCI) clinical features and identify key prognostic factors, thereby providing an empirical foundation for advancing prevention and treatment strategies and ultimately improving clinical outcomes for CCI patients.MethodsWe retrospectively analyzed 17,645 AIS and 7,584 AMI patients admitted to two hospitals from 2014 to 2023. Univariate analysis, Spearman correlation, and multivariate logistic regression were performed to identify independent risk factors. Receiver operating characteristic (ROC) curves were used to determine optimal cutoff values.ResultsThis study enrolled 85 patients with CCI, representing an overall CCI incidence of approximately 0.34%. Males comprised 64.71% of the cohort. ST-segment elevation myocardial infarction and cardiogenic cerebral infarction were the most predominant subtypes. The in-hospital mortality rate was 30.59%, with 65.38% of deaths attributed to cardiac causes. Multivariate logistic regression analysis identified three independent risk factors for in-hospital mortality: elevated neutrophil-to-lymphocyte ratio (NLR), decreased serum albumin, and increased peak N-terminal pro-B-type natriuretic peptide levels (NT-proBNP). ROC curve analysis demonstrated that the area under the curve (AUC) for the NLR, albumin concentration and peak NT-proBNP concentration were 0.863, 0.723, and 0.824, respectively. The optimal cutoff values were 6.914 for NLR, 33.80 g/L for albumin, and 9474.50 pg/mL for peak NT-proBNP. The AUC of the combined diagnostic model reached 0.959, significantly outperforming the individual indicators.ConclusionElevated NLR, decreased serum albumin, and increased peak NT-proBNP levels independently predict in-hospital mortality in CCI patients. Combining these biomarkers enhances predictive capability for adverse outcomes.

BackgroundTerminalia chebula Retz, known as the King of Tibet, is considered a functional food in China, celebrated for its antioxidant, immune-modulating, antibacterial, and anti-inflammatory properties. Chebulinic acid, derived from aqueous extracts of Terminalia chebula Retz, is known for its anti-inflammatory properties. However, its potential as an anti-Helicobacter pylori (HP) agent has not been fully explored.MethodsHerein, we extracted the main compound from Terminalia chebula Retz using a semi-preparative liquid chromatography (LC) system and identified compound 5 as chebulinic acid through Ultra-high performance liquid chromatography-MS/MS (UPLC–MS/MS) and Nuclear Magnetic Resonance (NMR). To evaluate its role, we conducted minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays, scanning electron microscope (SEM) imaging, inhibiting kinetics curves, urea fast test, cell counting kit-8 (CCK-8) assay, western blot analysis, griess reagent system, and molecular docking.ResultsOur results showed that chebulinic acid effectively inhibited the growth of the HP strain ATCC 700392, damaged the HP structure, and exhibited selective antimicrobial activity without affecting normal epithelial cells GES-1. Importantly, it suppressed the expression of Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Molecular docking analysis predicted a strong affinity (−9.7 kcal/mol) between chebulinic acid and Cag A protein.ConclusionOverall, our findings suggest that chebulinic acid acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, which is a critical step in HP infection. It also suppresses the Cag A protein. These results highlight the potential of chebulinic acid against HP infections.

Accurate three-dimensional spatiotemporal distribution information on near-surface aerosols is of great significance for environmental research. In this study, a 3D scanning coaxial Mie lidar (3D-STML) was developed to achieve a fast three-dimensional scanning observation of aerosol diffusion processes in near-surface areas. 3D-STML generates high-spatiotemporal resolution images of aerosol extinction coefficient in real-time and captures the dynamic changes of aerosols in near real-time. By optimizing the design of the light guide mirror and the telescope sub-mirror, the system has a small overlap. Based on this, a highly stable and high-speed mechanical rotation mechanism was developed to enable three-dimensional observations. The integration of a solid-state high-repetition-rate pulsed laser and a coaxial, optical system for the transmitter and receiver ensures rapid tracking of aerosol plumes. To meet the observation requirements of near-surface aerosols, an aerosol inversion algorithm combining the Fernald and Klett methods was designed and developed. For aerosol plume monitoring needs, an aerosol plume-tracking algorithm based on Kalman filtering was developed to track the spatiotemporal evolution of aerosols automatically. Experimental results demonstrated that 3D-STML is capable of detecting aerosols in a range from 15 m to 4 km, with a distance resolution of 1.5 m and a time resolution of 0.083 s. It can effectively track and capture aerosol plumes. It can be used for large-scale, long-term observation of near-surface aerosols and for monitoring the spatiotemporal evolution of aerosol plumes.

ObjectiveThis study aimed to compare clinical features, laboratory findings, and immunotherapy responses between antibody-positive and antibody-negative Autoimmune encephalitis (AE) patients.MethodsA retrospective analysis of clinical data from 60 AE patients (33 antibody-positive, 27 antibody-negative) diagnosed at Zhongshan Hospital of Xiamen University between January 1, 2016, and March 1, 2024 was conducted. Disease severity and treatment response were assessed using the modified Rankin Scale (mRS) and the Clinical Assessment Scale for Autoimmune Encephalitis (CASE).ResultsAntibody-positive AE patients more frequently presented with multiple symptoms (≥4 symptoms: 39.4% vs. 14.8%, p = 0.036). They demonstrated significantly elevated serum IgG concentrations (p = 0.010) and cerebrospinal fluid (CSF) leukocyte counts (p = 0.014). Conversely, antibody-negative AE patients presented with higher CSF total protein levels (p = 0.025) and albumin quotients (p = 0.018), indicative of more severe blood–brain barrier disruption. Antibody-positive AE patients more frequently received combination first-line immunotherapy (75.8% vs. 48.1%, p = 0.027) and exhibited superior treatment outcomes (90.9% vs. 70%, p = 0.022). Among critically ill patients (peak mRS score: 4–5), improvement in CASE scores was markedly greater in the antibody-positive cohort (median: 4.50 vs. 1.00, p = 0.024).ConclusionAntibody-positive AE patients manifested a more diverse symptom spectrum, elevated serum IgG concentrations and CSF leukocyte counts, and superior responses to immunotherapy. In contrast, antibody-negative AE patients demonstrated more severe blood–brain barrier dysfunction, as evidenced by higher CSF total protein concentrations and albumin quotients.

An organoid culture system better recapitulates the cellular structure, function, and interaction between cells and the extracellular matrix (ECM) than a two-dimensional (2D) culture system. We here constructed a condylar cartilage organoid to explore the regulatory role of primary cilia. Similar to the natural condylar cartilage, the condylar cartilage organoid exhibited abundant ECM and comprised superficial, proliferative, and hypertrophic zones. Primary cilia in the condylar cartilage organoid were shorter on average than those in the 2D culture chondrocytes, but their average length was equivalent to those in the natural condylar cartilage. Notably, primary cilia in each zone of the condylar cartilage organoid had an average length similar to that of primary cilia in the natural condylar cartilage. According to transcriptomic and biochemical analyses, the expression of cilia-related genes and cilia-related Hedgehog (HH) signaling differed between the condylar cartilage organoid and 2D culture systems. IFT88 knockdown promoted the protein levels of COL-Ⅹ, TRPV4, and HH signaling molecules in the condylar cartilage organoid, but decreased them in the 2D culture system. Notably, the protein levels of COL-Ⅹ, TRPV4, and HH signaling molecules increased in the superficial zone of the si IFT88 condylar cartilage organoid compared with the condylar cartilage organoid. However, the protein levels of aforementioned molecules were not significantly different in proliferative and hypertrophic zones. Collectively, we successfully constructed the condylar cartilage organoid with a better tissue structure and abundant ECM. Moreover, the condylar cartilage organoid is more suitable for exploring primary cilia functions.

The neonicotinoid pesticide acetamiprid has been widely used in agricultural pest control and was frequently detected in the water environment. There have been some studies of the toxic effects of acetamiprid on fish, but studies on aquatic lower vertebrates are still very limited.As a primitive jawless vertebrate, Lethenteron reissneri has a special position in evolution and is now listed as a national second level protected animal in China. The present study aimed to investigate the toxic effect of acetamiprid on the liver of L. reissneri larvae. A conjoint analysis of the transcriptomics and metabolomics was performed to determine the responses of L. reissneri larvae liver to acetamiprid at different concentrations (L for low concentration 25 mg/L and H for high concentration 100 mg/L). Even low concentrations of acetamiprid can cause significant liver damage to L. reissneri larvae in a short period. In omics analyses, 2141 differentially expressed genes (DEGs) and 183 differentially abundant metabolites (DAMs) were identified in the H/Control group, and 229 DEGs and 144 DAMs were identified in the L/C group. Correlation analyses revealed acetamiprid affected the metabolic pathways of L. reissneri larvae liver such as the glycerophospholipid metabolism and arachidonic acid metabolism. This study not only enriches the basis for understanding the toxic effect of acetamiprid exposure to L. reissneri larvae liver and provides more information on the breeding and conservation of L. reissneri, but also further causes attention on toxicity risk from acetamiprid to aquatic lower vertebrate species.

Halophytes face continuous challenges from environmental salt conditions throughout their lifecycle, and adaptive strategies are essential for their growth and survival. Hordeum brevisubulatum, a halophytic forage grass, relies on efficient K+ uptake for salt tolerance, as demonstrated by the inducible expression of HbHAK2 (high affinity K+ transporter 2). Using genome walking, we isolated a unique 744-bp HbHAK2 promoter, distinct from the upstream sequences of HvHAK2 in barley. Transgenic Arabidopsis plants carrying the GUS gene, driven by the HbHAK2 promoter, exhibited higher activity in tissues and cells exhibiting polar growth, including root hairs, lateral root initiation sites, trichomes, and shoot apical meristems (SAM), particularly under various stresses compared to control conditions. In both Arabidopsis and Brachypodium distachyon, the expression of HbHAK2, driven by its promoter (proHbHAK2) improved K+ uptake, promoted a root architecture characterized by increased lateral branching, and enhanced salt tolerance by augmenting the root system (including lateral roots and root-hair development and growth) under salt stress. Therefore, variation in the HbHAK2 promoter represents a specific strategy for halophytic H. brevisubulatum to cope with salt stress, which holds potential for improving salt tolerance in crop breeding programs.

Epilepsy is a chronic neurological disease. Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient diagnosed as epilepsy caused by ATP1A2 gene mutation. Induced pluripotent stem cells (iPSCs) were developed using non-integrating episomal vectors containing OCT4, SOX2, KLF4, BCL-XL and C-MYC. The established iPSC line (SDCHi007-A) displayed pluripotent cell morphology, high expression levels of pluripotency markers, differentiation potential in vitro, normal karyotype, and remaining the original ATP1A2 gene mutation.

In advancing the practical application of photocatalytic degradation for pollutant removal, batch preparation of environmentally friendly photocatalysts plays a crucial role. Herein, we prepared C/P co-doped urchin-like TiO2 (C/P–TiO2) through a straightforward room temperature impregnation and atmospheric annealing process. Phytic acid served as the dopant precursor for introducing C and P onto the TiO2 surface. This doping process was verified through energy dispersive X-ray spectroscopy (EDX), electron spin resonance (ESR), and X-ray photoelectron spectroscopy (XPS) analysis. The C/P–TiO2 photocatalyst exhibited exceptional efficiency in degrading the target compound trimethoprim (TMP), achieving a degradation of 98% TMP within 60 min and a mineralization of 40% TMP within 120 min, which were respectively 2.4 and 1.6 times higher than that of pristine TiO2. The intermediate products of TMP were detected, and a plausible degradation pathway was proposed. Photoelectric characterization results also confirmed that C/P co-doping could effectively enhance the carrier separation efficiency of C/P–TiO2. The catalysts prepared using the scaled-up impregnation system and reusing the phytic acid solution consistently demonstrated stable catalytic performance, which confirmed the viability of the method for green and batch preparation of C/P co-doped TiO2. Notably, the obtained catalyst consistently exhibited high degradation efficacy in various real water bodies, highlighting its substantial potential for practical application. The green and batch preparation method of C/P–TiO2 introduces a novel approach to the practical application of photocatalysis technology in treatment of water contaminants.

Abstract Background Diabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities of the heart and ultimately evolves to heart failure. IL-37 exerts a substantial influence on the regulation of inflammation and metabolism. Whether IL-37 is involved in DCM is unknown. Methods The plasma samples were collected from healthy controls, diabetic patients and DCM patients, and the level of IL-37 and its relationship with heart function were observed. The changes in cardiac function, myocardial fibrosis and mitochondrial injury in DCM mice with or without IL-37 intervention were investigated in vivo. By an in vitro co-culture approach involving HG challenge of cardiomyocytes and fibroblasts, the interaction carried out by cardiomyocytes on fibroblast profibrotic activation was studied. Finally, the possible interactive mediator between cardiomyocytes and fibroblasts was explored, and the intervention role of IL-37 and its relevant molecular mechanisms. Results We showed that the level of plasma IL-37 in DCM patients was upregulated compared to that in healthy controls and diabetic patients. Both recombinant IL-37 administration or inducing IL-37 expression alleviated cardiac dysfunction and myocardial fibrosis in DCM mice. Mechanically, hyperglycemia impaired mitochondria through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA. Fibroblasts then engulfed these mtDNA-enriched vesicles, thereby activating TLR9 signaling and the cGAS-STING pathway to initiate pro-fibrotic process and adverse remodeling. However, the presence of IL-37 ameliorated mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, resulting in a reduction in release of mtDNA-enriched vesicle and ultimately attenuating the progression of DCM. Conclusions Collectively, our study demonstrates a protective role of IL-37 in DCM, offering a promising therapeutic agent for this disease. Graphical abstract Hyperglycemia aggravates mitochondrial injury through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA in DCM mice. Fibroblasts then engulf these mtDNA-enriched vesicles, activating TLR9 signaling and the cGAS-STING pathway to initiate profibrotic process and adverse remodeling. However, both exogenous and endogenous IL-37 ameliorate mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, and reducing the release of mtDNA-enriched vesicles, which attenuates the progression of DCM

Mentougou District, the core region of Xishan in Beijing, is located at the junction of Yanshan and Taihang mountains, where mountainous areas account for 98.5%. Over the long geological history, it has remained rich geoheritages. The lack of systematic analysis on the distribution characteristics and evolution of geoheritages constraint their protection and utilization of geoheritages in this area. This study has systematically reviewed the types of geoheritages in this area through remote sensing, ground investigation, and rock and mineral identification. The results show that: (1) The rich geoheritages in this area are diverse; 100 types of geoheritages have been identified, including geological profiles, geological structures, paleontological fossils, and landscape geology. (2) The distribution of geological profile types such as the Qingbaikou Series and Malan loess is closely related to the exposure area of the Mesoproterozoic-Quaternary strata. Folds and faults are mainly distributed in the middle and high mountain areas from Miaofengshan Town to Zhaitang Town; the acidic rock mass of Yanshan period are mainly distributed along large faults; loess terraces, river terraces, gorges, and water landscape are mainly distributed along the main channel of the Yongdinghe River and its major tributaries. (3) Multiple marine intrusions in this area created lots of stratigraphic profile relics; the Qin Yu Movement, Jixian Movement, and Yanshan Movement led to many structural features, faults, and folds, which dominated the formation of multiple mineral deposits. This study can provide basic information for further in-depth research on geoheritages and their protection and utilization in this area.

Abstract Background The hair follicle is a skin accessory organ that regulates hair development, and its activity varies on a regular basis. However, the significance of metabolites in the hair follicle cycle has long been unknown. Results Targeted metabolomics was used in this investigation to reveal the expression patterns of 1903 metabolites in cashmere goat skin during anagen to telogen. A statistical analysis was used to investigate the potential associations between metabolites and the hair follicle cycle. The findings revealed clear changes in the expression patterns of metabolites at various phases and in various feeding models. The majority of metabolites (primarily amino acids, nucleotides, their metabolites, and lipids) showed downregulated expression from anagen (An) to telogen (Tn), which was associated with gene expression, protein synthesis and transport, and cell structure, which reflected, to some extent, that the cells associated with hair follicle development are active in An and apoptotic in An–Tn. It is worth mentioning that the expression of vitamin D3 and 3,3’,5-triiodo-L-thyronine decreased and then increased, which may be related to the shorter and longer duration of outdoor light, which may stimulate the hair follicle to transition from An to catagen (Cn). In the comparison of different hair follicle development stages (An, Cn, and Tn) or feeding modes (grazing and barn feeding), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that common differentially expressed metabolites (DEMs) (2’-deoxyadenosine, L-valine, 2’-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5’-monophosphate) were enriched in ABC transporters. This finding suggested that this pathway may be involved in the hair follicle cycle. Among these DEMs, riboflavin is absorbed from food, and the expression of riboflavin and sugars (D-glucose and glycogen) in skin tissue under grazing was greater and lower than that during barn feeding, respectively, suggesting that eating patterns may also alter the hair follicle cycle. Conclusions The expression patterns of metabolites such as sugars, lipids, amino acids, and nucleotides in skin tissue affect hair follicle growth, in which 2’-deoxyadenosine, L-valine, 2’-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5’-monophosphate may regulate the hair follicle cycle by participating in ABC transporters. Feeding practices may regulate hair follicle cycles by influencing the amount of hormones and vitamins expressed in the skin of cashmere goats.

Abstract Immune checkpoint inhibition targeting the PD-1/PD-L1 pathway has become a powerful clinical strategy for treating cancer, but its efficacy is complicated by various resistance mechanisms. One of the reasons for the resistance is the internalization and recycling of PD-L1 itself upon antibody binding. The inhibition of lysosome-mediated degradation of PD-L1 is critical for preserving the amount of PD-L1 recycling back to the cell membrane. In this study, we find that Hsc70 promotes PD-L1 degradation through the endosome-lysosome pathway and reduces PD-L1 recycling to the cell membrane. This effect is dependent on Hsc70-PD-L1 binding which inhibits the CMTM6-PD-L1 interaction. We further identify an Hsp90α/β inhibitor, AUY-922, which induces Hsc70 expression and PD-L1 lysosomal degradation. Either Hsc70 overexpression or AUY-922 treatment can reduce PD-L1 expression, inhibit tumor growth and promote anti-tumor immunity in female mice; AUY-922 can further enhance the anti-tumor efficacy of anti-PD-L1 and anti-CTLA4 treatment. Our study elucidates a molecular mechanism of Hsc70-mediated PD-L1 lysosomal degradation and provides a target and therapeutic strategies for tumor immunotherapy.

Abstract Background The risk factors for hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT) are unclear. Therefore, we conducted this systematic review and meta-analysis to investigate the risk factors for HC in children undergoing HSCT. Methods We performed this meta-analysis by retrieving studies from PubMed, EMBASE, and the Cochrane Library up to October 10, 2023, and analyzing those that met the inclusion criteria. I2 statistics were used to evaluate heterogeneity. Results Twelve studies, including 2,764 patients, were analyzed. Male sex (odds ratio [OR] = 1.52; 95% confidence interval [CI], 1.16–2.00; p = 0.003, I2 = 0%), allogeneic donor (OR = 5.28; 95% CI, 2.60–10.74; p

Precipitation strengthening plays a vital role in enhancing the mechanical properties of metallic materials, typically achieved through heat treatment. However, deformation-induced precipitation (DIP) in multicomponent alloys (MAs) without the assistance of annealing is rarely reported, owing to their inherent high entropy and sluggish diffusion effects. This work reveals the significant formation of nanoscale and microscale precipitates in the dual-phase Fe49.3Co23Ni23C0.85Mn1Si2.85 MA triggered by surface severe plastic deformation (SSPD) through industrial shot blasting. The SSPD process leads to the formation of ultrafine gradient structures comprising nanocrystalline and submicron-crystalline zones. Submicron SiO2 precipitates emerge at the interfaces of both these zones, while various Mn5Si3 and Si nanoparticles precipitate within the nanocrystalline zone. This phenomenon can be ascribed to the high density of generated substructures, the accelerated diffusion of atoms, and the reduction in solid solubility limits in the SPD-driven non-equilibrium state.

Abstract Background Understanding of the ratio of photosynthetic photon flux density (Q p ) to global solar radiation (R s ) (Q p /R s ) is crucial for applying R s to ecology-related studies. Previous studies reported Q p /R s and its variations based on measurements from a single observatory tower, instead of multi-site-based measurements over complex terrains. This may neglect spatial heterogeneity in the terrain, creating a gap in an understanding of how terrain affects Q p /R s and how this effect interacts with meteorological factors. Methods Here the Qingyuan Ker Towers (three towers in a valley with different terrains: T1, T2, and T3) were utilized to measure Q p and R s over mountainous forests of Northeast China. An airborne LiDAR system was used to generate a digital elevation model, and sky view factor of sectors (SVFs) divided from the field of view of tower’s pyranometer was calculated as a topographic factor to explain the variations of Q p /R s . Results The results identified significant differences in Q p /R s of the three towers at both daily and half-hour scales, with larger differences on clear days than on overcast days. Q p /R s was positively correlated with SVFs of T1 and T3, while this correlation was negative with that of T2. The effect of SVFs on Q p /R s interacted with clearness index, water vapor pressure and solar zenith angle. Random forest-based importance assessment demonstrated that explanation (R 2) on Q p /R s was improved when SVFs was included in the predictor variable set, indicating that incorporating terrain effects enhances the prediction accuracy of Q p /R s . The improvement in the R 2 values was more pronounced on clear days than on overcast days, suggesting that the effect of terrain on Q p /R s depended on sky conditions. Conclusions All findings suggested that Q p /R s is affected by terrain, and integrating terrain information into existing Q p /R s models is a feasible solution to improve Q p /R s estimates in mountainous areas.

Abstract Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.

In order to solve the favorable advance angle in the case of an uncertain homing range of torpedoes, the influence of homing range on torpedo firing was first analyzed. It was pointed out that when the actual homing range of torpedoes was less than its binding value, the favorable advance angle obtained from the calculation became smaller, and the probability of torpedo discovery was significantly reduced. Secondly, the weighted average discovery probability of torpedoes was defined. On this basis, a favorable advance angle calculation method was proposed to maximize the weighted average discovery probability. Then, according to the principle of maximum entropy, two maximum entropy distribution models for the actual homing range of torpedoes were given, and the formula for solving the favorable advance angle under this distribution model was obtained. Finally, the favorable advance angle in the case of an uncertain homing range of torpedoes was obtained through simulation.