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Abstract Drug resistance remains a significant challenge in cancer treatment. Recently, the interactions among various cell types within the tumor microenvironment (TME) have deepened our understanding of the mechanisms behind treatment resistance. Therefore, this review aims to synthesize current research focusing on infiltrating cells and drug resistance suggesting that targeting the TME could be a viable strategy to combat this issue. Numerous factors, including inflammation, metabolism, senescence, hypoxia, and angiogenesis, contribute to drug resistance could be a viable strategy to combat this issue. Overexpression of STAT3 is commonly associated with drug-resistant cancer cells or stromal cells. Current research often generalizes the impact of stromal cells on resistance, lacking specificity and statistical robustness. Thus, future research should take notice of this issue and aim to provide high-quality evidence. Despite the existing limitations, targeting the TME to overcome therapy resistance hold promising and valuable potential.

Abstract Red swamp crayfish, Procambarus clarkii, is the most cultured freshwater crayfish species. It attracts significant research attention due to its considerable economic importance. However, the limited availability of genome information has impeded further genetic studies and breeding programs. By utilizing Illumina, PacBio, and Hi-C sequencing technologies, we present a more comprehensive and continuous chromosome-level assembly for P. clarkii than the published one. The final genome size is 4.03 Gb, consisting of 2,358 scaffolds with a N50 of 42.87 Mb. Notably, 3.68 Gb, corresponding to 91.42% of the genome, was anchored to 94 chromosomes. The assembly comprises 70.64% repetitive sequences, including 5.21% tandem repeats and 65.40% transposable elements. Additionally, a total of 4,456 non-coding RNAs and 28,852 protein-coding genes were predicted in the P. clarkii genome, with 96.26% of the genes were annotated. This high-quality genome assembly not only represents a significant improvement for the genome of P. clarkii and provides insights into the unique genome evolution, but also offers valuable information for developing freshwater aquaculture and accelerating genetic breeding.

Abstract Hepatocellular carcinoma (HCC) is a significant global health challenge. The activation of autophagy plays an essential role in promoting the proliferation and survival of cancer cells. However, the upstream regulatory network and mechanisms governing autophagy in HCC remain unclear. This study demonstrated that histone deacetylase 2 (HDAC2) regulates autophagy in HCC. Its expression was elevated in HCC tissues, and high HDAC2 expression was strongly associated with poor prognosis in individuals with HCC. Integrated in vitro and in vivo investigations confirmed that HDAC2 promotes autophagy and autophagy-related malignant progression in HCC. Mechanistically, HDAC2 bound specifically to the lysosome-associated protein transmembrane 4-β (LAPTM4B) promoter at four distinct binding sites, enhancing its transcriptional activation and driving autophagy-related malignant progression in HCC. These findings establish LAPTM4B as a direct target gene of HDAC2. Furthermore, the selective inhibitor of HDAC2 effectively alleviated the malignant development of HCC. In addition, multivariate Cox regression analysis of 105 human HCC samples revealed that HDAC2 expression is an independent predictor of HCC prognosis. This study underscores the crucial role of the HDAC2-LAPTM4B axis in regulating autophagy in the malignant evolution of HCC and highlights the potential of targeting HDAC2 to prevent and halt the malignant progression of HCC.

Abstract Neonatal respiratory distress syndrome (NRDS) is one of the leading causes of neonatal mortality in low-income countries. It is caused by a lack of surface-active substances in the lungs, and the maternal inflammatory response plays an important role in the formation of surface-active substances in the fetal lungs. We aimed to investigate the correlation between maternal prenatal systemic inflammatory indices and respiratory distress syndrome in preterm neonates. This is a retrospective case–control study that collected data from all patients who delivered between 28 and 36 weeks of gestation at Longhua District People's Hospital in Shenzhen City and whose infants were admitted to the neonatal unit, newborns with respiratory distress syndrome were in the experimental group (NRDS group), and newborns without NRDS were in the control group (non-NRDS group). To minimize the effect of confounders on the results, propensity score matching was performed on baseline characteristics. Totally, 524 patients were included (93 in the NRDS group and 431 in the non-NRDS group), and 71 matched pairs (142 patients). The neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI) and neutrophil lymphocyte to platelet ratio (NLPR) were higher in the NRDS group than in the non-NRDS group (p

Abstract Clarification of the cytotoxic function of T cells is crucial for understanding human immune responses and immunotherapy procedures. Here, we report a high-throughput Bessel oblique plane microscopy (HBOPM) platform capable of 3D live imaging and phenotyping of chimeric antigen receptor (CAR)-modified T-cell cytotoxicity against cancer cells. The HBOPM platform has the following characteristics: an isotropic subcellular resolution of 320 nm, large-scale scouting over 400 interacting cell pairs, long-term observation across 5 hours, and quantitative analysis of the Terabyte-scale 3D, multichannel, time-lapse image datasets. Using this advanced microscopy platform, several key subcellular events in CAR-T cells are captured and comprehensively analyzed; these events include the instantaneous formation of immune synapses and the sustained changes in the microtubing morphology. Furthermore, we identify the actin retrograde flow speed, the actin depletion coefficient, the microtubule polarization and the contact area of the CAR-T/target cell conjugates as essential parameters strongly correlated with CAR-T-cell cytotoxic function. Our approach will be useful for establishing criteria for quantifying T-cell function in individual patients for all T-cell-based immunotherapies.

The insoluble dietary fiber (IDF) of grape skins was modified by high-temperature steaming combined with the snail enzyme method using grape skins as raw material, the aim of this study was to increase the yield of soluble dietary fiber (SDF) and improve the physicochemical properties of SDF and IDF. The effects of different factors on the yield of SDF were studied, and the physicochemical indexes of dietary fiber before and after modification were determined. The experimental results were as follows: Steaming time of 60 minutes, steaming temperature of 120 ℃, the material to liquid ratio was 1:25 g/mL, enzyme addition of 3.50%, enzymatic hydrolyswas temperature of 34.0 ℃, and enzymatic hydrolysis time of 55 minutes. Under these conditions, the yield of SDF was 10.25%. The water holding capacity, oil holding capacity, and swelling capacity of modified SDF were increased by 1.74, 1.53, and 1.13 times, respectively. The water holding capacity, oil holding capacity, and swelling capacity of the modified IDF were increased by 1.01, 1.26, and 1.27 times, respectively. Compared with the unmodified SDF and IDF, the structure of the modified SDF and IDF became more loose, and the glucose adsorption capacity, glucose dialysis retardation index, and α-amylase inhibition were significantly improved. Among them, the modified SDF had the strongest glucose adsorption capacity, and the glucose dialysis delay index was also higher than other dietary fiber samples. When the addition amount was 8 mg/mL, the inhibition rate of the modified SDF on α-amylase reaches its maximum value (54.71%). In summary, the modified SDF and modified IDF had better characteristics, which would provide a theoretical basis for modified grape skin dietary fiber.

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum (ER) presents an opportunity to amplify the synergistic effects of chemotherapy and immunotherapy. In this study, we initially validated celastrol (CEL) as an inducer of immunogenic cell death (ICD) by promoting ER stress and autophagy in colorectal cancer (CRC) cells. Subsequently, an ER-targeted strategy was posited, involving the codelivery of CEL with PD-L1 small interfering RNAs (siRNA) using KDEL peptide-modified exosomes derived from milk (KME), to enhance chemoimmunotherapy outcomes. Our findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER pathway. Compared to their non-targeting counterparts, KME exhibited a significant augmentation of the CEL-induced ICD effect. Additionally, it facilitated the release of danger signaling molecules (DAMPs), thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the tumor. Concurrently, the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression, consequently fostering the proliferation and activity of CD8+ T cells. Ultimately, the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in vivo. Collectively, a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

Abstract Diabetic nephropathy (DN) is a common secondary kidney disease. Immune and inflammatory responses play an influential role in the development of DN. This study aims to explore the role and mechanisms of immune- and inflammatory-related factors in DN. Participants from the NHANES 2013–2018 were included to evaluate the association between the SII and DN. Considering the skewed distribution of SII, log SII was used for subsequent analysis. Then, the DEGs were extracted from the GSE96804 dataset by the “limma” package of R, which were further screened out genes in the key module based on WGCNA. The intersection genes between DEGs and key module genes were the key genes for the following mechanism exploration. The CyTargetlinker plug-in of Cytoscape software was used to construct the drug-genes network. Molecular docking was used to calculate the binding affinity between potential drugs and the hub genes. Among the 8236 participants from NHANES 2013–2018, Log SII was significantly associated with DN (p

According to previous studies, D-dimer levels are associated with the prognosis of patients with pancreatic cancer (PC). However, the results of current studies are limited and controversial. Therefore, we performed this meta-analysis to assess the relationship between D-dimer levels and prognostic and pathological characteristics of PC patients. We first searched the databases of PubMed, Embase, The Cochrane Library, Web Of Science, CBM, VIP, CNKI and Wanfang to identify available studies. The relationship between pretreatment d-dimer levels and prognosis in PC patients was assessed using the combined hazard ratio (HR) and 95% confidence interval (CI). The combined odds ratio (OR) and 95% confidence interval (CI) were used in assessing the relationship between pathological characteristics and d-dimer levels in PC patients. Stata 12.0 software was used for all statistical analyses. In total, we included 13 studies involving 2777 patients. The results showed that elevated pre-treatment d -dimer levels were significantly associated with OS deterioration (HR = 1.46 95% CI: 1.34–1.59; p

Abstract Background Healthcare-associated infections (HAIs) are important indicators of healthcare quality. The aseptic non touch technique (ANTT), a standardised aseptic technique, is a crucial preventative measure against HAIs. However, there is insufficient evidence currently available regarding ANTT awareness and proficiency among nurses. This study aimed to investigate the status of ANTT proficiency in a cohort of nurses and analyse the associated risk factors, with the ultimate goal of providing a reference for promoting the application of ANTT in clinical practice. Methods The study population was sampled from nurses working in a tertiary hospital in Zhejiang Province, China, in January 2024. A cross-sectional survey was conducted using a self-designed questionnaire to assess ANTT knowledge. Multivariate linear regression analysis was used to analyse the risk factors influencing ANTT knowledge in nurses. Results A total of 458 nurses were included in this study. The cohort had an overall score of 49.7% correct responses on the ANTT knowledge questionnaire, with a mean score of 12.4 ± 2.4 out of 25, and 30.1% of the nurses felt that they did not need training related to ANTT. Multivariate linear regression analysis indicated that professional title, educational level, and the need for ANTT training were independently associated with ANTT knowledge in nurses. Nurses with Master’s degrees and associated chief nurses were observed to have higher levels of ANTT knowledge compared to the rest. Conclusions ANTT knowledge is insufficient among nurses in China, and its importance is not widely recognised. Continuous efforts are required to strengthen this knowledge. Constructing sustained, multiform, and stratified training programmes may represent an effective method to strengthen ANTT knowledge among nurses and promote its clinical use.

Abstract Objective Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. Methods Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). Results The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. Conclusion The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

Abstract Vibrio spp. are major pathogens responsible for mortality and disease in various marine aquaculture organisms. Effective disease control and genetic breeding strategies rely heavily on understanding host vibriosis resistance mechanisms. The Chinese tongue sole (Cynoglossus semilaevis) is economically vital but suffers from substantial mortalities due to vibriosis. Through continuous selective breeding, we have successfully obtained vibriosis-resistant families of this species. In this study, we conducted RNA-seq analysis on three organs, including liver, spleen and intestine from selected resistant and susceptible tongue soles. Additionally, we integrated these data with our previously published RNA-seq datasets of skin and gill, enabling the construction of organ-specific transcriptional profiles and a comprehensive gene co-expression network elucidating the differences in vibriosis resistance. Furthermore, we identified 12 modules with organ-specific functional implications. Overall, our findings provide a valuable resource for investigating the molecular basis of vibriosis resistance in fish, offering insights into target genes and pathways essential for molecular selection and genetic manipulation to enhance vibriosis resistance in fish breeding programs.

Abstract HRB500E rebar is a low-alloy high-strength steel with excellent mechanical properties and good plasticity but suffers from deficient corrosion resistance. This can be solved by adding trace elements, including rare earth elements. Herein, the corrosion-resistant behavior of rebar was evaluated by weightlessness testing and electrochemical measurements, and the effects of Ce on the structural evolution of the corrosion product layer were investigated by scanning electron microscopy (SEM), Electron Probe X-ray Micro-Analyzer (EPMA), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The results showed that adding Ce to the rebar improved the densification of the reinforcing surface corrosion products, as well as reduced the corrosion rate of the experimental rebar. Compared to C0 sample without Ce, the rebar sample containing 0.044 wt.% Ce displayed increased Ecorr by 0.051 V, decreased Icorr by 15.573 mA cm−2, enhanced Rc of the corrosion product layer by 112.71 Ω cm2, incremented α-FeOOH content in the corrosion product layer, and boosted ratio of α/γ* in the corrosion product layer by 10.11%. Furthermore, the oxide (CeO2) formed by Ce in the corrosion layer of the rebar bar surface existed in the rust layer, resulting in a stable corrosion product layer with improved blocking ability of the corrosive medium. Overall, the addition of Ce at certain ratios looks promising to produce HRB500E rebar with excellent corrosion resistance and extended service life under harsh conditions.

Abstract Background The cranial-caudal-medial approach (CCMA) has been proposed for laparoscopic right hemicolectomy nowadays. This study aimed to investigate the safety and oncological efficacy of CCMA in the treatment of right-sided colon cancer compared to the medial–lateral approach (MLA). Methods Patients diagnosed with right-sided colon cancer were included from February 2015 to June 2018, retrospectively, dividing into the CCMA group and the MLA group. We compared the basic characteristics and the short-term and long-term outcomes in two groups. Results Two hundred and ninety-six patients were included in this study. The baseline characteristics were similar in two groups. Compared with MLA group, CCMA group exhibited shorter operation time (136.3 ± 25.3 min vs. 151.6 ± 21.5 min, P

Abstract Contemporary studies in polarization multiplexing are hindered by the intrinsic orthogonality constraints of polarization states, which restrict the scope of multiplexing channels and their practical applications. This research transcends these barriers by introducing an innovative nonorthogonal polarization-basis multiplexing approach. Utilizing spatially varied eigen-polarization states within metaatoms, we successfully reconstruct globally nonorthogonal channels that exhibit minimal crosstalk. This method not only facilitates the generation of free-vector holograms, achieving complete degrees-of-freedom in three nonorthogonal channels with ultra-low energy leakage, but it also significantly enhances the dimensions of the Jones matrix, expanding it to a groundbreaking 10 × 10 scale. The fusion of a controllable eigen-polarization engineering mechanism with a vectorial diffraction neural network culminates in the experimental creation of 55 intricate holographic patterns across these expanded channels. This advancement represents a profound shift in the field of polarization multiplexing, unlocking opportunities in advanced holography and quantum encryption, among other applications.

Abstract In this study, the immersion test, surface analysis, cross-section analysis, quantitative analysis and electrochemical analysis were used to study the influence of Nb/V on the corrosion behavior of high-strength anti-seismic rebar in marine environments. The corrosion results clarified that the addition of Nb/V improved the corrosion resistance of the rebar, thereby reducing the corrosion rate of the rebar and improving the stability of corrosion layers. Firstly, the addition of Nb/V promoted the transformation of unstable Fe oxyhydroxides to stable Fe oxyhydroxides in the surface corrosion layers of the rebar, thus increasing the α/(β + γ) ratio, corrosion potential and total impedance value. Secondly, the addition of Nb/V induced the formation of Nb oxides and V oxides in the surface corrosion layers of the rebar, and the existence of these oxides repaired the surface defects of corrosion layers, thus enhancing the corrosion resistance performance of surface corrosion layers of the rebar.

Abstract Background SARS-CoV-2 infection in pregnant women during the third trimester resulted in overall adverse pregnancy outcomes compared to non-infected controls and a unique humoral and cellular response at delivery. In this study we aimed to assess the impact of SARS-CoV-2 infection on maternal/neonatal peripartum outcomes andimmunological profiles. Method In this study, we recruited 304 SARS-CoV-2 infected pregnant women and 910 SARS-CoV-2 non-infected pregnant women who were admitted for delivery. Peripartum and neonates’ outcomes response to SARS-CoV-2 infection were analyzed. Furthermore, we characterized the antibody and cytokines profile in SARS-CoV-2 infected maternal blood (MB) and cord blood (CB). We also assessed routine laboratory tests and liver function tests in MB before labor. Unpaired T test, Mann-Whitney test and Spearman test were used to analyze the data. Results SARS-CoV-2 infected pregnant women were significantly associated with increased risk of adverse pregnancy outcomes, including preterm labor (13.8% vs. 9.5%, p = 0.033) and meconium-stained amniotic fluid (8.9% vs. 5.5%, p = 0.039). The risk of low birth weight (

ObjectiveTo evaluate the efficacy and further analyze the application prospects of the combined multitarget fecal FIT-DNA assay in the early screening of colorectal cancer. MethodsSubjects were selected from a population attending the Inner Mongolia Medical University Hospital. Each subject underwent a combined multi-target fecal FIT-DNA test (experimental group), a serum tumor marker test and enteroscopy (control group). The pathological results were used as the gold standard to evaluate the efficacy of novel fecal molecular testing techniques for colorectal cancer screening with timely intervention given to screen positive individuals. ResultsThe data of 115 individuals were analyzed. Serum tumor markers test had a sensitivity of 63.2% (43/68) and a specificity of 74.5% (35/47). The enteroscopy had a sensitivity of 97.1% (66/68) and a specificity of 80.7% (38/47); the combined multitarget fecal FIT-DNA test had a sensitivity of 89.7% (61/68) and a specificity of 87.2% (41/47). ConclusionThe sensitivity and specificity of multitarget fecal FIT-DNA combined detection are better than those of serum tumor marker detection. Although its sensitivity is lower than enteroscopy, its operation is simpler and can be tested at home.

Abstract Background Metabolic syndrome (MetS) presents a notable public health challenge on a global scale, exerting a considerable impact on individuals’ health and quality of life. There is mounting evidence indicating a robust association between MetS and levels of sex hormones. Therefore, the study aims to explore the relationship between sex hormone binding-globulin (SHBG) and MetS, and to provide evidence that could inform the development of effective prevention strategies for MetS. Methods Data for this cross-sectional investigation were collected during the 2013–2016 cycle of the National Health and Nutrition Examination Survey (NHANES), from which 5,499 adults were sampled. The criteria established by the Adult Treatment Program III of the National Cholesterol Education Program were utilized to define MetS. SHBG levels were measured using a standardized technique. Multivariate-adjusted logistic regression, multivariate restricted cubic spline, and threshold effect analyses were utilized to investigate the association between SHBG levels and MetS. Moreover, the stratified analyses and interaction tests of covariables were presented in a forest plot. Finally, sensitivity analysis was utilized to ensure the robustness of the results. Results Overall, 1822 participants had MetS. After adjusting for possible confounders, SHBG levels were associated with MetS (Odds ratio [OR], 0.984; 95% confidence interval [CI], 0.981–0.986; P

Abstract In recent years, the precisely controlled synthesis of chiral twisted molecular carbons has emerged as a forefront topic in the research of carbon materials. Molecular carbons refer to carbon nanomaterials synthesized with precision at the atomic level. Through rational design, rigid and stable chiral twisted structures can be synthesized. The exploration in the field of chiral twisted molecular carbons is key to fully understanding the various twisted configurations of carbon materials and delving into the relationship between structure design and functionality. This review explores chiral twisted configurations of carbon nanomaterials such as nanographene, carbon nanobelts, carbon nanosheets, graphdiyne, etc. It emphasizes the role of photocyclization, Scholl reaction, and Diels–Alder reactions in achieving precise chiral control and discusses a range of innovative design strategies. These strategies have led to the development of various twisted structures, such as helical, propeller, and Möbius strip configurations. The introduction of chirality, combined with the inherent exceptional optical properties of nanocarbon materials, has facilitated the creation of materials with superior chiroptical performances. This advancement is driving applications in fields such as optoelectronics and chiral optics.

Abstract Circadian rhythm disorder (CRD) is closely associated with hair regression and shedding, but whether this risk can be transmitted to the offspring is unknown. Whether Pu‐erh tea, with alleviating effects of CRD‐mediated syndrome, can act on the transmission of alopecia risk to offspring is also unproven. Here, we obtained CRD parental mice offspring and found that CRD‐mediated alopecia risk can be transmitted to offspring, especially male offspring. Parental consumption of Pu‐erh tea, especially in females or both parents, reduced the risk of CRD‐mediated alopecia transmitted to offspring by inhibiting subcutaneous fat accumulation (downregulation of Rab18, fat‐specific protein 27 (Fsp27), and perilipin 1 (Plin1)), reducing oxidative stress and inflammation in skin tissue (NADPH oxidase 4 (NOX4)/ nuclear factor kappa‐B (NF‐κB)), balancing androgen and hair growth factor release (hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin‐like growth factor 1 (IGF‐1)), and restoring hair follicle DNA repair function (upregulation of Ku70, 8‐Oxoguanine DNA glycosylase 1 (OGG1), and Rad51). Transcriptomic analysis further clarified that the mechanism stemmed from the upregulation of gene expression in pathways such as the Wnt, Hippo, and other signaling pathways.

Abstract Cellular senescence is characterized by a decrease in protein synthesis, although the underlying processes are mostly unclear. Chemical modifications to transfer RNAs (tRNAs) frequently influence tRNA activity, which is crucial for translation. We describe how tRNA N7-methylguanosine (m7G46) methylation, catalyzed by METTL1-WDR4, regulates translation and influences senescence phenotypes. Mettl1/Wdr4 and m7G gradually diminish with senescence and aging. A decrease in METTL1 causes a reduction in tRNAs, especially those with the m7G modification, via the rapid tRNA degradation (RTD) pathway. The decreases cause ribosomes to stall at certain codons, impeding the translation of mRNA that is essential in pathways such as Wnt signaling and ribosome biogenesis. Furthermore, chronic ribosome stalling stimulates the ribotoxic and integrative stress responses, which induce senescence-associated secretory phenotype. Moreover, restoring eEF1A protein mitigates senescence phenotypes caused by METTL1 deficiency by reducing RTD. Our findings demonstrate that tRNA m7G modification is essential for preventing premature senescence and aging by enabling efficient mRNA translation.

Abstract Genetic code expansion has emerged as a powerful tool for precisely introducing unnatural chemical structures into proteins to improve their catalytic functions. Given the high catalytic propensity of histidine in the enzyme pocket, increasing the chemical diversity of catalytic histidine could result in new characteristics of biocatalysts. Herein, we report the genetically encoded Nδ-Vinyl Histidine (δVin-H) and achieve the wild-type-like incorporation efficiency by the evolution of pyrrolysyl tRNA synthetase. As histidine usually acts as the nucleophile or the metal ligand in the catalytic center, we replace these two types of catalytic histidine to δVin-H to improve the performance of the histidine-involved catalytic center. Additionally, we further demonstrate the improvements of the hydrolysis activity of a previously reported organocatalytic esterase (the OE1.3 variant) in the acidic condition and myoglobin (Mb) catalyzed carbene transfer reactions under the aerobic condition. As histidine is one of the most frequently used residues in the enzyme catalytic center, the derivatization of the catalytic histidine by δVin-H holds a great potential to promote the performance of biocatalysts.

Abstract To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P

The deintercalation of weakly bonded A element affects the microstructure and properties of MAX phases and their reinforced composites. In this work, the effect of M-site element on the interaction of Al-containing M2AlC (M = V, Cr) phase and Ag, and the induced properties of Ag/M2AlC electrical contact materials (ECMs) were investigated. Though Ag and Al are soluble to each other and can form intermetallics, the variation of M element significantly affected the vacancy formation of Al, and thereby the interfacial reaction of Ag/M2AlC. The difficult formation of Al vacancy in V2AlC contributed to no obvious interfacial reaction in Ag/V2AlC. But the easy deintercalation of Al atoms in Cr2AlC led to their massive replacement by Ag, which generated Ag nano-twins and Cr3C2 with the same crystallographic relationship in one original Cr2AlC, and Cr7C3 and Ag3Al as well. Due to the distinct interactions, the resistivities of Ag/V2AlC and Ag/Cr2AlC increased by roughly 1 and 5 times after sintering, respectively. The low resistivity and proper hardness of the sintered Ag/V2AlC, which were very close to those of the “all-purpose” commercial Ag/CdO, contributed to its superior arc erosion resistance.

In this study, the synergistic effect of the Nb content and cooling rate on the microstructural transformation, precipitation behavior, and mechanical properties of hot-rolled rebar was studied using a Gleeble-3800 thermal simulation machine, scanning electron microscopy, transmission electron microscopy, and a universal tensile testing machine. The results showed that the synergistic effect of Nb content and cooling rate could optimize the microstructure and precipitation behavior of rebar, promote ferrite and pearlite transformation, and reduce the ferrite grain size, pearlite lamellar spacing, and precipitated phase size, thereby improving the strength and plasticity of Nb-containing rebar. When the cooling rate was 3 °C/s and the Nb content was 0.035 wt%, the ferrite grain size decreased to 21.45 μm, the pearlite lamellar spacing refined to 0.222 μm, and the particle size of the (Nb, Ti, V) C precipitates reduced to 5 nm. Accordingly, the yield and tensile strength increased to 779 ± 6 MPa and 973 ± 8 MPa, respectively, the elongation at fracture increased to 16.35%, and the microhardness increased to 311.39 ± 8.0 HV.

Abstract Aims Few studies have investigated differences in sequential transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and simultaneous RFA‐TACE for the treatment of hepatocellular carcinoma (HCC) using the Milan criteria. This study explored the differences in safety and prognosis between sequential TACE‐RFA and simultaneous RFA‐TACE. Methods This retrospective real‐world study included 109 patients with HCC within the Milan criteria who underwent sequential TACE‐RFA (n = 75) or simultaneous RFA‐TACE (n = 34) at the Eastern Hepatobiliary Surgery Hospital between January 2017 and 2021. Postoperative complications, length of hospital stay, and long‐term prognosis were compared. The median follow‐up duration of these patients was 39.1 months. Overall survival (OS) and time to tumor recurrence (TTR) curves were plotted using the Kaplan−Meier method and were compared using the logarithmic rank test. Independent risk factors for OS and tumor recurrence (TR) were analyzed using the Cox risk regression model. Results Multivariate analysis showed that tumor diameter >3 cm (hazard ratio [HR]: 2.201, 95% confidence interval [CI]: 1.106–4.378, p = 0.025; HR: 2.236, 95% CI: 1.271–3.934, p = 0.005, respectively) and alpha‐fetoprotein (AFP) > 400 μg/L (HR: 2.362, 95% CI: 1.195–4.668, p = 0.013; HR: 1.798, 95% CI: 1.048–3.086, p = 0.033, respectively) were independent risk factors for OS and TTR, whereas the presence of multiple tumors (HR: 2.352, 95% CI: 1.127–4.907, p = 0.023) was an independent risk factor for TTR. Simultaneous RFA‐TACE did not have an effect on OS or TTR. After propensity score‐matched, comparable results were obtained and RFA‐TACE still had no effect on OS or TTR. No significant differences were observed in grade III/IV complications (2/75 [2.7%] vs. 1/34 [2.9%], p = 1.000) between the two groups. However, the RFA‐TACE group had fewer complications than the TACE‐RFA group (24/34 [70.6%] vs. 66/75 [88.0%], p = 0.026). The RFA‐TACE group had a shorter hospital stay and less total cost during hospitalization compared with the TACE‐RFA group (6.0 vs. 10.0 days, p

Abstract Yuxi, located in China’s central plateau of Yunnan, is grappling with ecological and environmental challenges as it continues to develop its economy. While ecological quality assessment serves as the foundation for ecological protection, it is pivotal to have reliable and long-term methods for assessing the ecological status to support informed decision-making in ecological protection. Reliable and long-term methods for assessing ecological status in order to facilitate informed decision-making in ecological protection are applied. This study utilized Landsat data to reconstruct four indices (greenness, wetness, dryness, and heat) during the vegetation growth in Yuxi from 2000 to 2020 that employs Harmonic Analysis of Time Series (HANTS) method. Subsequently, the annual Remote Sensing Ecological Index (RSEI) was computed by using the reconstructed indices to evaluate ecological quality in Yuxi. Additionally, spatiotemporal patterns and determinants of Yuxi’s ecological quality are unveiled through Sen’s slope estimator and Mann–Kendall test (Sen + MK) trend analysis, spatial auto-correlation analysis, and geographical detectors applied to year-by-year RSEI data. The findings in the paper indicate that the accuracy of the RSEI is significantly influenced by the vegetation season, suggesting that constructing the RSEI model with data from the vegetation growth season is crucial. Moreover, the HANTS optimization method effectively enhances the ecological indices used in the RSEI model, leading to smoother and more continuous filling of missing data. The difference between the reconstructed RSEI and the original RSEI falls within the range of − 0.15 to 0.15. Yuxi has an average RSEI of 0.54 to emphasis a moderate level of comprehensive ecological quality. Compared with river valley plains, the ecological quality of mountainous areas is higher, and the ecological quality of Yuxi presents a distinct center-edge pattern. From 2000 to 2020, Yuxi’s ecological quality exhibited fluctuations, with a slight overall improvement. Land use patterns, particularly in forestry land and impervious surfaces, are identified as the main drivers of these changes. The research offers valuable insights for scientific decision-making related to sustainable development and ecological protection.

Abstract Hydrothermal carbonization (HTC) has been regarded as a promising technique for turning wet biomass into hydrochar due to its low energy consumption, low exhaust gas emissions, etc. In addition, hydrochar is an important source of dissolved organic matter (DOM), which plays a crucial part in the migration and destiny of pollutants in the environmental medium. However, there are limited studies that focus on the factors that influence the formation of DOM in hydrochar, such as hydrothermal temperature. Therefore, the current study comprehensively characterized the optical properties of DOM within hydrochar derived from sawdust (HDOM) under different hydrothermal temperatures (150–300 °C) by Ultraviolet–visible (UV–Vis) and fluorescence spectroscopy, as well as its complexation characteristic with Cu(II). The findings revealed that the organic carbon content of HDOM reached a peak of 37.3 mg L−1 when the temperature rose to 240 °C and then decreased as the temperature increased. UV–Vis spectroscopy analysis showed that the absorption capacity of HDOM at 275 nm increases with temperature and reaches a maximum value at 240 °C, indicating that high temperature promotes the formation of monocyclic aromatic compounds. High temperature enhances the aromaticity, hydrophobicity, and humification degree of HDOM, thus improving its stability and aromaticity. The E3/E4 ratios are all greater than 3.5, confirming that the main component of HDOM is fulvic acid, which corresponds to 3D-EEM and Pearson's correlation coefficient analysis. The humification index (HIX) of HDOM increased with the rise in hydrothermal temperature (150–240 °C), as observed by the three-dimensional excitation-emission matrix spectroscopy (3D-EEMs). After reaching its peak at 240 °C, the HIX value gradually dropped in line with the trend of the DOC change. Moreover, the bioavailability (BIX) value of DOM was all high and greater than 1, indicating all the HDOM are readily bioavailable. Two microbial humic substances (C1 and C4), a humic-like substance (C2), and a protein-like substance (C3) were discovered in DOM by integrating 3D-EEMs with parallel factor analysis (PARAFAC). Their fluorescence intensity decreases as the Cu(II) concentration increases, indicating the formation of complexes with Cu(II). As the temperature rises, the binding ability of DOM and Cu(II) changes significantly, reaching the optimum at 300 °C. Meanwhile, the substance C2 has the strongest binding ability with Cu(II). This research emphasizes the significance of spectroscopy analysis in determining the evolution of hydrochar-derived DOM, the potential for heavy metal binding and migration, and its characteristics and features. Graphical Abstract

Abstract This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

The razor clam (Sinonovacula constricta, Class Bivalvia) is a kind of burial filter-feeding shellfish. Salinity fluctuation is an important source of pressure for water habitats. High salinity in some coastal areas of Shandong and Jiangsu impact the survival and germplasm conservation of razor clam. To study the ecological behavior response of S. constricta to high salt culture environment, two populations of razor clams were used, including "Shenzhe No.1" population (SZSC) and a natural population (ZRSC). The semi-lethal salinity level of each population was determined. The effects of control group (20) and high salinity (24, 28, 32) on burrowing and feeding behavior of razor clams were studied. The differences in burrowing indices and feeding physiology between the two populations were compared. In the burrowing behavior experiment, two groups were set; razor clams from the temporary pond were put into each salinity group to start the experiment, while the other group of razor clams were stressed under each salinity condition for 24 h and then put into each salinity group to start the experiment. The results showed that the 120 h LC50 of SZSC was 34.04, while the 120 h LC50 of ZRSC was 32.04. The burrowing behavior of razor clams could be divided into four periods: The preparation period of shell closure, the period of axe foot movement, mud digging period, and the end period of mud diving. In the non-stressed group, the burrowing time of 50% (BT50) of SZSC was significantly higher than that of ZRSC (P0.05). The BT50 of SZSC was closer to that of the control group at 24 and 28 salinity, and the vitality of SZSC was significantly better than that of ZRSC after 24 h of salinity stress. Under high salinity, the distribution of SZSC in mud was more concentrated than that in ZRSC, and the burrowing depth was shallower. In terms of feeding physiology, the feeding rate of SZSC was significantly higher than that of ZRSC under high salinity (P

Abstract Background Cytoplasmic male sterility (CMS) has greatly improved the utilization of heterosis in crops due to the absence of functional male gametophyte. The newly developed sporophytic D1 type CMS (CMS-D1) rice exhibits unique characteristics compared to the well-known sporophytic CMS-WA line, making it a valuable resource for rice breeding. Results In this research, a novel CMS-D1 line named Xingye A (XYA) was established, characterized by small, transparent, and shriveled anthers. Histological and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays conducted on anthers from XYA and its maintainer line XYB revealed that male sterility in XYA is a result of delayed degradation of tapetal cells and abnormal programmed cell death (PCD) of microspores. Transcriptome analysis of young panicles revealed that differentially expressed genes (DEGs) in XYA, compared to XYB, were significantly enriched in processes related to chromatin structure and nucleosomes during the microspore mother cell (MMC) stage. Conversely, processes associated with sporopollenin biosynthesis, pollen exine formation, chitinase activity, and pollen wall assembly were enriched during the meiosis stage. Metabolome analysis identified 176 specific differentially accumulated metabolites (DAMs) during the meiosis stage, enriched in pathways such as α-linoleic acid metabolism, flavone and flavonol biosynthesis, and linolenic acid metabolism. Integration of transcriptomic and metabolomic data underscored the jasmonic acid (JA) biosynthesis pathway was significant enriched in XYA during the meiosis stage compared to XYB. Furthermore, levels of JA, MeJA, OPC4, OPDA, and JA-Ile were all higher in XYA than in XYB at the meiosis stage. Conclusions These findings emphasize the involvement of the JA biosynthetic pathway in pollen development in the CMS-D1 line, providing a foundation for further exploration of the molecular mechanisms involved in CMS-D1 sterility.

Abstract Background Intraventricular hemorrhage (IVH) refers to bleeding within the brain’s ventricular system, and hydrocephalus is a life-threatening complication of IVH characterized by increased cerebrospinal fluid accumulation in the ventricles resulting in elevated intracranial pressure. IVH poses significant challenges for healthcare providers due to the complexity of the underlying pathophysiology and lack of standardized treatment guidelines. Herein, we performed a systematic review of the treatment strategies for hydrocephalus secondary to IVH. Methods This systematic review was prospectively registered with PROSPERO (CRD42023450786). The search was conducted in PubMed, Cochrane Library, and Web of Science on July 15, 2023. We included original studies containing valid information on therapy management and outcome of hydrocephalus secondary to primary, spontaneous, and subarachnoid or intracranial hemorrhage following IVH in adults that were published between 2000 and 2023. Glasgow Outcome Scale (GOS) or modified Ranking Scale (mRS) scores during follow-up were extracted as primary outcomes. The risk of bias was assessed using the Newcastle–Ottawa Scale for Cohort Studies or Cochrane Risk of Bias 2.0 Tool. Results Two hundred and seven patients from nine published papers, including two randomized controlled trials, were included in the analysis. The GOS was used in five studies, while the mRS was used in four. Seven interventions were applied, including craniotomy for removal of hematoma, endoscopic removal of hematoma with/without endoscopic third ventriculostomy (ETV), traditional external ventricular drainage (EVD), and various combinations of EVD, lumbar drainage (LD), and intraventricular fibrinolysis (IVF). Endoscopic removal of hematoma was performed in five of nine studies. Traditional EVD had no obvious benefit compared with new management strategies. Three different combinations of EVD, LD, and IVF demonstrated satisfactory outcomes, although more studies are required to confirm their reliability. Removal of hematoma through craniotomy generated reliable result. Generally, endoscopic removal of hematoma with ETV, removal of hematoma through craniotomy, EVD with IVF, and EVD with early continuous LD were useful. Conclusion EVD is still crucial for the management of IVH and hydrocephalus. Despite a more reliable result from the removal of hematoma through craniotomy, a trend toward endoscopic approach was observed due to a less invasive profile.

Abstract Developing mild photocatalytic bromination strategies using sustainable bromo source has been attracting intense interests, but there is still much room for improvement. Full utilization of redox centers of photocatalysts for efficient generation of Br+ species is the key. Herein we report heterogenous organophotocatalytic HBr oxidation coupled with oxygen reduction to furnish Br2 and H2O2 for effective bromination of arenes over Al2O3 supported perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA). Mechanism studies suggest that O-vacancy in Al2O3 can provide Lewis-acid-type anchoring sites for O2, enabling unexpected dual-electron transfer from anchored photoexcited PTCDA to chemically bound O2 to produce H2O2. The in-situ generated H2O2 and Br2 over redox centers work together to generate HBrO for bromination of arenes. This work provides new insights that heterogenization of organophotocatalysts can not only help to improve their stability and recyclability, but also endow them with the ability to trigger unusual reaction mode via cooperative catalysis with supports.

Abstract Background Diabetic sarcopenia is a disease‐related skeletal muscle disorder that causes progressive symptoms. The complete understanding of its pathogenesis is yet to be unravelled, which makes it difficult to develop effective therapeutic strategies. This study investigates how MFG‐E8 affects mitophagy and the protective role of D‐pinitol (DP) in diabetic sarcopenia. Methods In vivo, streptozotocin‐induced diabetic SAM‐R1 (STZ‐R1) and SAM‐P8 (STZ‐P8) mice (16‐week‐old) were used, and STZ‐P8 mice were administrated of DP (150 mg/kg per day) for 6 weeks. Gastrocnemius muscles were harvested for histological analysis including transmission electron microscopy. Proteins were evaluated via immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) assay. In vitro, advanced glycation end products (AGEs) induced diabetic and D‐galactose (DG) induced senescent C2C12 models were established and received DP, MFG‐E8 plasmid (Mover)/siRNA (MsiRNA), or 3‐MA/Torin‐1 intervention. Proteins were evaluated by IF and WB assay. Immunoprecipitation (IP) and co‐immunoprecipitation (CO‐IP) were used for hunting the interacted proteins of MFG‐E8. Results In vivo, sarcopenia, mitophagy deficiency, and up‐regulated MFG‐E8 were confirmed in the STZ‐P8 group. DP exerted protective effects on sarcopenia and mitophagy (DP + STZ‐P8 vs. STZ‐P8; all P

In order to study the effect of hypoxia combined with acid stress on GABA enrichment in adzuki bean and mung bean, germination time, germination temperature, hypoxia time and L-glutamic acid concentration were investigated by single factor. Based on the stress conditions identified for high GABA sprouted beans, GABA-enriched adzuki and mung beans were mixed with rice, and D-mixture design was used to optimize processing conditions for these sprouted bean/rice mixtures. Results showed that hypoxia combined with acid stress promoted GABA enrichment in adzuki and mung beans. In sprouted adzuki beans, GABA reached levels as high as 158.32±3.24 mg/100 g under the germination time of 48 h, germination temperature of 40 ℃, 15 h exposure to hypoxia, and L-glutamic acid concentration of 2.5 mg/mL. Mung bean stress conditions were: Germination time of 24 h, germination temperature of 35 ℃, 15 h exposure to hypoxia, and L-glutamic acid concentration of 2.5 mg/mL, the content of GABA was 141.57±4.35 mg/100 g. On this basis, the sprouted beans and rice formulation was optimized by D-mixture design as follows: Rice 76%, sprouted mung beans 11%, and sprouted adzuki beans 13%. Under this composition, the GABA content of sprouted bean/rice mixture was 23.73±1.03 mg/100 g, and the average sensory score was 88.76±2.47. The taste, color, and aroma of the sprouted bean/rice mixture fell within acceptable ranges, and the active ingredient GABA was enriched, enhancing the nutritional and functional properties of sprouted beans/rice. This study provided a theoretical reference for the further development of rice/grain mixtures.

The prevalent practice of substituting fishmeal with plant protein frequently leads to disturbances in bile acid metabolism, subsequently increasing the incidence of metabolic liver diseases. Bile acid nutrients such as cholesterol, taurine and glycine have been shown to enhance bile acid synthesis and confer beneficial effects on growth. Therefore, this study aimed to investigate the effects of cholesterol-taurine-glycine (Ch-Tau-Gly) supplement on bile acid metabolism and liver health in spotted seabass (Lateolabrax maculatus) fed a plant-based diet. Two isonitrogenous and isolipidic diets were formulated: (1) plant protein-based diet (PP); (2) PP supplemented 0.5% cholesterol, 0.5% taurine and 1.3% glycine (CTG). Each experimental diet was randomly fed to quadruplicate groups of 30 feed-trained spotted seabass in each tank. The results revealed that supplementing plant-based diet with Ch-Tau-Gly supplement led to an increase in carcass ratio (meat yield) in spotted seabass (P

At the altitude of low-Earth-orbiting satellites, most details of lithospheric magnetic anomalies observed near surface are attenuated, and only slowly decaying long-wavelength magnetic anomalies can be detected. Long-wavelength magnetic anomalies are generated by large-scale magnetized rocks in the Earth's crust and uppermost mantle at depths shallower than the Curie depth. Interpretation of such lithospheric magnetic anomalies has been used in geological mapping, crustal composition and structure studies, plate tectonic reconstruction, and geodynamics. To introduce the origin of long-wavelength magnetic anomalies at a global scale, we first reviewed satellite magnetic anomaly maps in early periods and calculated anomaly maps using four main lithospheric magnetic field models, including the CHAOS-7, CM6, MF7, and CSES models. Then, based on the result of the CHAOS-7 model at 500 km altitude, 29 long-wavelength magnetic anomalies with amplitudes greater than 4 nT were identified and their geological origins were reviewed. Among these, there were twenty magnetic anomalies over continents and nine over the ocean. The long-wavelength magnetic anomalies over continental areas were mostly located in Precambrian basements related to the Archean nuclei, Proterozoic terrane, and iron-rich formations, with a few located in the orogenic background. The long-wavelength magnetic anomalies in the ocean region were all located in oceanic plateau, generally related to the breakup of Gondwana during the Cretaceous Period, and have the characteristics of thickened crust. Hence, the long-wavelength magnetic anomalies reveal a significant magnetization difference in the deep crust during crustal growth, a key issue that requires further study. Compared to satellite magnetic surveys in some other nations, detecting lithospheric magnetic anomalies by satellite started relatively late in China. The China Seismo-Electromagnetic Satellite (CSES) was launched in February 2018. It was China's first satellite designed to monitor earthquakes with multiple geophysical payloads, including magnetometers capable of measuring weak signals from the lithosphere. The Macau Science Satellite-1 (MSS-1) was launched in 2023 and is specially used for monitoring the geomagnetic field in low latitudes. Furthermore, a subsequent CSES-02 satellite is planned to be launched in 2024. With the vigorous development of satellite magnetic surveys in China, it is expected that progressively more Chinese researchers will pay attention to long-wavelength magnetic anomalies and promote the study of their origin.

Low Earth orbit (LEO) satellites have emerged as a primary tool for global geomagnetic field detection and model refinement, owing to their wide coverage, high resolution, and absence of geographical limitations. This paper provides a comprehensive review of the history, key characteristics, measurement accuracy, and future trends in LEO satellite magnetic field measurements. The first part of the paper outlines the evolution of LEO satellites, highlighting their unique advantages. The focus then shifts to the calibration methodology for in-orbit LEO satellite magnetic measurements, with a specific emphasis on vector magnetic field intrinsic calibration and alignment algorithms. Calibration results are presented to demonstrate the effectiveness of these methodologies. In the third section, the paper introduces the theory behind global geomagnetic field modeling. An overview of current global geomagnetic field models is provided, encompassing their sources, spatial resolutions, and other relevant attributes. The paper concludes by presenting the global morphology and features of the main field, lithospheric field, magnetospheric, and ionospheric field. Despite the significant progress enabled by LEO satellite technology, global geomagnetic field modeling faces challenges such as limited spatio-temporal resolution. To address this, incorporating near-surface observation data and continuously optimizing modeling technology are deemed essential solutions.

Isothermal heat treatment experiments were used to studied the dissolution behavior and kinetics of the γ′ precipitates within the hot-extruded novel powder metallurgy Ni-based superalloy A1. The characteristics of the γ′ precipitates were accurately and rapidly extracted by deep learning methods. The JMAK models were established to predict the change of the area fraction of γ′ precipitates during heat treatment. The determination coefficient R2 of model is 0.99. The results indicate that the dissolution sequence, morphological evolution, and dissolution mechanisms of the three types of γ′ precipitates are different. The small-sized tertiary γ′ precipitates (γ′t) dissolve first, while the larger-sized primary γ′ precipitates (γ′p) dissolve last. After 15 min at 1120 °C, there were only a small amount of γ′ precipitates with 0.19 ± 0.03 % area fraction. And there was not significant changed over time. After 1 min at 1150 °C, the γ′ precipitates completely dissolved. During the process of low temperature subsolvus heat treatment (1060 °C, 1090 °C), the large-sized γ′s grown at the expense of consuming the small-sized γ′ precipitates, and the γ′s tend towards directional arrangement due to elastic interaction energy. During the subsolvus heat treatment process, the γ′p spilt due to elastic strain energy and the uneven diffusion of alloying elements, while neck-connected coalescence coarsening occurs due to the overlapping diffusion fields.

Groundwater is a crucial water resource for various usages worldwide. The Quetta Valley of Pakistan was investigated regarding its groundwater quality sustainability based on integrated approaches of hydrochemistry, geographic information system, and multivariate statistics. A total of 29 groundwater samples were collected from monitoring wells to get insights into the hydrochemical suitability of groundwater for sustainable irrigation and drinking utilization. The results indicate groundwater is mainly featured by the hydrochemical facies of HCO3·Cl-Ca. Groundwater hydrochemical composition is dominantly governed by the dissolution of carbonates and silicate minerals in combination with positive cation exchange in the valley. Principal component analysis reveals a significant influence of geogenic factors on groundwater chemistry, further supported by PHREEQC simulation that detects a supersaturation of calcite, dolomite, and sulphate minerals in the aquifer. The irrigation water quality index divides groundwater in the study area into three zones, which signify low restriction and no restriction, except for a severe restriction in the southwestern part of the valley. Groundwater is generally suitable for irrigation across the valley. The entropy-weighted water quality index classifies groundwater as excellent and good quality for drinking. This study can provide crucial insights for authorities on groundwater suitability in Quetta Valley and similar regions worldwide. HIGHLIGHTS Traditional hydrochemical techniques integrated with multivariate statistical analysis and Geographic Information System (GIS)-based methods were employed to provide a nuanced understanding of hydrochemical parameters and their spatial distribution.; Hydrochemical fingerprints were recognized to assess groundwater quality for drinking and irrigation purposes.; The irrigation water quality index delineates zones for irrigation suitability, while the entropy-weighted water quality index ranks water quality for drinking purposes.;

Geochemistry of noble gases has been applied to the study of deep Earth materials and celestial meteorites. With advancements in measurement technology, it is also increasingly being used in natural gas research. Using the most advanced noble gas mass spectrometer, a systematic analysis was conducted on the abundance and isotopes of noble gas samples collected from the middle and deep Songliao Basin in eastern China to elucidate the compositional characteristics of noble gases in a faulted basin. The findings reveal that the abundance of noble gases in natural gas decreases from light noble gases to heavy noble gases in a left-to-right reversed L-shaped pattern. Specifically, the isotopic ratios of noble gases are: 3He/4He at 2.64×10-6, 20Ne/22Ne at 9.94, 21Ne/22Ne at 0.029 22, and 40Ar/36Ar at 743.7, all of which are higher than atmospheric values. The isotopes 80Kr, 84Kr, 86Kr, and 131-136Xe show relative excess compared to atmospheric levels, indicating the mixing of mantle-derived gases in the natural gas. Based on the compositional characteristics of noble gases, this study suggests that the natural gas in the middle and deep Songliao Basin originated from inorganic crust and mantle mixing. Additionally, certain differences exist in the contribution of mantle-derived components across different tectonic blocks and categories of natural gas within the basin. Comparison between noble gas compositions and the types of natural gas demonstrates that light noble gases distinguish effectively between different types of natural gas, whereas the composition of heavy noble gases shows no significant differences among various types of natural gas. Noble gas isotopes, in addition to tracing the source of natural gas, can also be used to determine natural gas genesis, distinguish natural gas types and characterize tectonic settings.

Abstract In the past decade, intestinal organoid technology has paved the way for reproducing tissue or organ morphogenesis during intestinal physiological processes in vitro and studying the pathogenesis of various intestinal diseases. Intestinal organoids are favored in drug screening due to their ability for high-throughput in vitro cultivation and their closer resemblance to patient genetic characteristics. Furthermore, as disease models, intestinal organoids find wide applications in screening diagnostic markers, identifying therapeutic targets, and exploring epigenetic mechanisms of diseases. Additionally, as a transplantable cellular system, organoids have played a significant role in the reconstruction of damaged epithelium in conditions such as ulcerative colitis and short bowel syndrome, as well as in intestinal material exchange and metabolic function restoration. The rise of interdisciplinary approaches, including organoid-on-chip technology, genome editing techniques, and microfluidics, has greatly accelerated the development of organoids. In this review, VOSviewer software is used to visualize hot co-cited journal and keywords trends of intestinal organoid firstly. Subsequently, we have summarized the current applications of intestinal organoid technology in disease modeling, drug screening, and regenerative medicine. This will deepen our understanding of intestinal organoids and further explore the physiological mechanisms of the intestine and drug development for intestinal diseases.

Abstract Objective Understanding the characteristics related to cardiorespiratory fitness after stroke can provide reference values for patients in clinical rehabilitation exercise. This meta- analysis aimed to investigate the effect of robot-assisted gait training in improving cardiorespiratory fitness in post-stroke patients, compared to conventional rehabilitation training. Methods PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, CBM, CNKI and Wanfang databases were searched until March 18th, 2024. Randomized controlled trials (RCTs) comparing the effectiveness of robot-assisted gait training versus control group were included. The main outcome variable was peak oxygen uptake. 6-minute walking test, peak heart rate, peak inspiratory expiratory ratio as our secondary indicators. RevMan 5.3 software was used for statistical analysis. Results A total of 17 articles were included, involving 689 subjects. The results showed a significant effect for robot-assisted gait training to improve VO2peak (MD = 1.85; 95% CI: -0.13 to 3.57; p = 0.04) and 6WMT (MD = 19.26; 95% CI: 10.43 to 28.08; p

Abstract To reduce the local scour around the spur dike, the U-shaped collar is proposed in this study. The influence of the collar's length, width, and porosity on the local scour reduction in clear water is studied by model tests and numerical simulations. Experimental studies show that the collar has a significant effect on reducing the local scour. The location of the maximum scour depth of the spur dike moves downstream. The width of the collar has the greatest impact on the reduction effect among the three selected factors, followed by the porosity and the length. Local scour reduction efficiency of the collar can reach 56.9%. Based on the regression analysis of the range and variety, a formula for predicting the reduction effect around the spur dike is put forward, and the deviation between the values by formula and that in experiments are within ± 4%. The characteristics of the flow field around the spur dike under constant conditions with a collar are studied via numerical simulation. The numerical simulation results show that compared to the case without collar, the flow velocities around the spur dike in cases with permeable collar and solid collar reduced by 45% and 25%, respectively, and the shear stresses reduced by 20% and 28.6%, respectively. The results of this study can provide a reference for local scour reduction using the solid collar or collar made of permeable materials such as gabions.

Abstract A long-standing hypothesis proposes that certain RNA(s) must exhibit structural roles in microtubule assembly. Here, we identify a long noncoding RNA (TubAR) that is highly expressed in cerebellum and forms RNA–protein complex with TUBB4A and TUBA1A, two tubulins clinically linked to cerebellar and myelination defects. TubAR knockdown in mouse cerebellum causes loss of oligodendrocytes and Purkinje cells, demyelination, and decreased locomotor activity. Biochemically, we establish the roles of TubAR in promoting TUBB4A–TUBA1A heterodimer formation and microtubule assembly. Intriguingly, different from the hypomyelination-causing mutations, the non-hypomyelination-causing mutation TUBB4A-R2G confers gain-of-function for an RNA-independent interaction with TUBA1A. Experimental use of R2G/A mutations restores TUBB4A–TUBA1A heterodimer formation, and rescues the neuronal cell death phenotype caused by TubAR knockdown. Together, we uncover TubAR as the long-elusive structural RNA for microtubule assembly and demonstrate how TubAR mediates microtubule assembly specifically from αβ-tubulin heterodimers, which is crucial for maintenance of cerebellar myelination and activity.

Abstract This cross-sectional study aimed to explore the knowledge, attitude and practice (KAP) toward sleep disorders and sleep hygiene among perimenopausal women, who were enrolled in Dezhou region of Shandong Province between July and September 2023. A total of 720 valid questionnaires were collected (mean age: 51.28 ± 4.32 years old), and 344 (47.78%) reported experiencing insomnia. The mean scores for knowledge, attitude, practice, and Dysfunctional Beliefs and Attitudes about Sleep (DBAS) were 15.73 ± 7.60 (possible range: 0–36), 29.35 ± 3.15 (possible range: 10–50), 28.54 ± 4.03 (possible range: 10–50), and 6.79 ± 1.90 (possible range: 0–10), respectively. Path analysis showed that knowledge had direct effects on attitude (β = 0.04, 95% CI 0.01–0.07, P = 0.001), and DBAS (β = 0.04, 95% CI 0.02–0.05, P

Abstract Background Cellular immunotherapy, represented by the chimeric antigen receptor T cell (CAR-T), has exhibited high response rates, durable remission, and safety in vitro and in clinical trials. Unfortunately, anti-CD19 CAR-T (CART-19) treatment alone is prone to relapse and has a particularly poor prognosis in relapsed/refractory (r/r) B-ALL patients. To date, addressing or reducing relapse remains one of the research priorities to achieve broad clinical application. Methods We manufactured second generation CART-19 cells and validated their efficacy and safety in vitro and in vivo. Through co-culture of Nalm-6 cells with short-term cultured CART-19 cells, CD19-negative Nalm-6 cells were detected by flow cytometry, and further investigation of the relapsed cells and their resistance mechanisms was evaluated in vitro. Results In this study, we demonstrated that CART-19 cells had enhanced and specific antileukemic activities, and the survival of B-ALL mouse models after CART-19 treatment was significantly prolonged. We then shortened the culture time and applied the serum-free culture to expand CAR-T cells, followed by co-culturing CART-19 cells with Nalm-6 cells. Surprisingly, we observed the proliferation of CD19-negative Nalm-6 cells around 28 days. Identification of potential resistance mechanisms showed that the relapsed cells express truncated CD19 proteins with decreased levels and, more importantly, CAR expression was detected on the relapsed cell surface, which may ultimately keep them antigen-negative. Furthermore, it was validated that CART-22 and tandem CART-22/19 cells could effectively kill the relapsed cells, but neither could completely eradicate them. Conclusions We successfully generated CART-19 cells and obtained a CD19-negative refractory relapsed B-ALL cell line, providing new insights into the underlying mechanisms of resistance and a new in vitro model for the treatment of r/r B-ALL patients with low antigen density.

In this study, 304 antimicrobial stainless steel coatings were prepared by the electron beam melting of antimicrobial stainless steel powder, in an attempt to enhance the surface properties of Q345R steel. Besides, the effect of Cu-containing 304 powder coatings on the microstructure, mechanical properties, and electrochemical properties of the Q345R surface was investigated. The results indicated that the coating grain was refined, the dislocation density was increased, and both the plasticity and toughness were enhanced after the electron beam surface coating (EBSC) treatment. Additionally, the hardness of coatings was also enhanced under the three beam currents due to grain refinement and dislocation strengthening. At a beam current of 28 mA, the coating hardness reached a maximum of 384.078 HV, representing a two-fold increase compared with the base material (BM) hardness of 131.048 HV. Moreover, the abrasion resistance of the coating was superior to that of the BM. At a beam current of 28 mA, the wear volume and wear rate were minimized to only 10 % of the wear volume of substrates. In galvanic corrosion measurements, the coatings displayed better corrosion resistance than the substrates, and these samples at a beam current of 28 mA exhibited the best corrosion resistance. Overall, the E-beam surface melting 304 stainless steel coating can effectively improve the properties of Q345R carbon steel.