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Abstract Background Commensal bacteria in the intestine release enzymes to degrade and ferment dietary components, producing beneficial metabolites. However, the regulatory effects of microbial-derived enzymes on the intestinal microbiota composition and the influence on host health remain elusive. Xylanase can degrade xylan into oligosaccharides, showing wide application in feed industry. Results To validate the immune-protective effects of xylanase, Nile tilapia was used as the model and fed with xylanase. The results showed that dietary xylanase improved the survival rate of Nile tilapia when they were challenged with Aeromonas hydrophila. The transcriptome analysis showed significant enrichment of genes related to interleukin-17d (il-17d) signaling pathway in the xylanase treatment group. High-throughput sequencing revealed that dietary xylanase altered the composition of the intestinal microbiota and directly promoted the proliferation of Allobaculum stercoricanis which could produce butyrate in vitro. Consequently, dietary xylanase supplementation increased the butyrate level in fish gut. Further experiment verified that butyrate supplementation enhanced the expression of il-17d and regenerating islet-derived 3 gamma (reg3g) in the gut. The knockdown experiment of il-17d confirmed that il-17d is necessary for butyrate to protect Nile tilapia from pathogen resistance. Flow cytometry analysis indicated that butyrate increased the abundance of IL-17D+ intestinal epithelial cells in fish. Mechanistically, butyrate functions as an HDAC3 inhibitor, enhancing il-17d expression and playing a crucial role in pathogen resistance. Conclusion Dietary xylanase significantly altered the composition of intestinal microbiota and increased the content of butyrate in the intestine. Butyrate activated the transcription of il-17d in intestinal epithelial cells by inhibiting histone deacetylase 3, thereby protecting the Nile tilapia from pathogen infection. This study elucidated how microbial-derived xylanase regulates host immune function, providing a theoretical basis for the development and application of functional enzymes. Video Abstract

Abstract CT and MR tools are commonly used to diagnose lumbar fractures (LF). However, numerous limitations have been found in practice. The aims of this study were to innovate and develop a spinal disease-specific neural network and to evaluate whether synthetic MRI of the LF affected clinical diagnosis and treatment strategies. A total of 675 LF patients who met the inclusion and exclusion criteria were included in the study. For each participant, two mid-sagittal CT and T2-weighted MR images were selected; 1350 pairs of LF images were also included. A new Self-pix based on Pix2pix and Self-Attention was constructed. A total of 1350 pairs of CT and MR images, which were randomly divided into a training group (1147 pairs) and a test group (203 pairs), were fed into Pix2pix and Self-pix. The quantitative evaluation included PSNR and SSIM (PSNR1 and SSIM1: real MR images and Pix2pix-generated MR images; PSNR2 and SSIM2: real MR images and Self-pix-generated MR images). The qualitative evaluation, including accurate diagnosis of acute fractures and accurate selection of treatment strategies based on Self-pix-generated MRI, was performed by three spine surgeons. In the LF group, PSNR1 and PSNR2 were 10.884 and 11.021 (p

Abstract Background The progression of tumours is related to abnormal phospholipid metabolism. This study is anticipated to present a fresh perspective for disease therapy targets of hepatocarcinoma caused by hepatitis B virus in the future by screening feature genes related to phospholipid metabolism. Methods This study analysed GSE121248 to pinpoint differentially expressed genes (DEGs). By examining the overlap between the metabolism-related genes and DEGs, the research focused on the genes involved in phospholipid metabolism. To find feature genes, functional enrichment studies were carried out and a network diagram was proposed. These findings were validated via data base of The Cancer Genome Atlas (TCGA). Further analyses included immune infiltration studies and metabolomics. Finally, the relationships between differentially abundant metabolites and feature genes were confirmed by molecular docking, providing a thorough comprehension of the molecular mechanisms. Results The seven genes with the highest degree of connection (PTGS2, IGF1, SPP1, BCHE, NR1I2, NAMPT, and FABP1) were identified as feature genes. In the TCGA database, the seven feature genes also had certain diagnostic efficiency. Immune infiltration analysis revealed that feature genes regulate the infiltration of various immune cells. Metabolomics successfully identified the different metabolites of the phospholipid metabolism pathway between patients and normal individuals. The docking study indicated that different metabolites may play essential roles in causing disease by targeting feature genes. Conclusions In this study, for the first time, it reveals the possible involvement of genes linked to phospholipid metabolism-related genes using bioinformatics analysis. Identifying genes and probable therapeutic targets could provide clues for the further treatment of disease.

Abstract Studying the spatial and temporal changes of grassland soil organic carbon (SOC) is helpful in promote the management of regional ecosystem carbon sinks. Grazing is one of the main ways of rational utilization of grassland. Different grazing intensities will affect the change of SOC density. Under different grazing intensity and management measures in Zhangye grassland, this study uses the parameter localized CENTURY model to simulate the temporal and spatial variations of SOC density from 1970 to 2022. The results showed that long-term light grazing reduced the average SOC by 195.114 g·m−2 and 1.91%. Moderate and severe grazing, respectively, for a long time made the total SOC density loss of 5.21% and 17.69%. In a short period, mild and moderate grazing reduced total SOC first and then increased it. Under light grazing, total SOC density appeared higher relative changes in the southeast, and lower in the northwest and central. There was no significant difference in the relative changes of total SOC between steppe and desert grasslands under light grazing. The decrease range of steppe was gradually greater than that in desert grassland. Since different management measures were implemented in some sampling sites in 2017, we divided the study period into two periods, 1970–2016 and 2017–2022. The implementation of degraded grassland improvement, fallow grazing, and rotational grazing would increase the total SOC density and mild SOC density, rotational grazing > degraded grassland improvement > rest grazing. Rotational grazing and the improvement of degraded grassland increased the density of active and inert SOC, while resting grazing decreased the density of SOC.

Abstract Background Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone. Case presentation A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic. Conclusions In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.

Abstract Background Mung bean (Vigna radiata L.) is an important warm-season grain legume. Adaptation to extreme environmental conditions, supported by evolution, makes mung bean a rich gene pool for stress tolerance traits. The exploration of resistance genes will provide important genetic resources and a theoretical basis for strengthening mung bean breeding. B-box (BBX) proteins play a major role in developmental processes and stress responses. However, the identification and analysis of the mung bean BBX gene family are still lacking. Results In this study, 23 VrBBX genes were identified through comprehensive bioinformatics analysis and named based on their physical locations on chromosomes. All the VrBBXs were divided into five groups based on their phylogenetic relationships, the number of B-box they contained and whether there was an additional CONSTANS, CO-like and TOC1 (CCT) domain. Homology and collinearity analysis indicated that the BBX genes in mung bean and other species had undergone a relatively conservative evolution. Gene duplication analysis showed that only chromosomal segmental duplication contributed to the expansion of VrBBX genes and that most of the duplicated gene pairs experienced purifying selection pressure during evolution. Gene structure and motif analysis revealed that VrBBX genes clustered in the same group shared similar structural characteristics. An analysis of cis-acting elements indicated that elements related to stress and hormone responses were prevalent in the promoters of most VrBBXs. The RNA-seq data analysis and qRT-PCR of nine VrBBX genes demonstrated that VrBBX genes may play a role in response to environmental stress. Moreover, VrBBX5, VrBBX10 and VrBBX12 are important candidate genes for plant stress response. Conclusions In this study, we systematically analyzed the genomic characteristics and expression patterns of the BBX gene family under ABA, PEG and NaCl treatments. The results will help us better understand the complexity of the BBX gene family and provide valuable information for future functional characteristics of specific genes in this family.

Liver fibrosis is a chronic liver disease that brings a heavy economic burden to the world and has attracted global attention. Although the pathological mechanisms and treatment strategies of liver fibrosis have been extensively studied, there are currently no effective targeted drugs for the prevention and treatment of liver fibrosis in clinical practice. Therefore, it is imperative to seek and develop effective treatment strategies and drugs for liver fibrosis. Magnoflorine (MAG) is a natural product with multiple pharmacological activities. Thus, in this study, we will explore the effect of MAG on alleviating liver fibrosis in mice and its mechanism of action. Our study indicates that MAG can alleviate liver damage, improve liver collagen deposition, and significantly reduced the expression levels of hepatic stellate cells (HSCs) activation markers in vivo. Additionally, the findings of this study indicate that MAG can inhibit the transforming growth factor-beta (TGF-β)/Smad signaling pathway. Bioinformatics analysis suggests that the alleviating effect of MAG on liver fibrosis may be associated with ferroptosis. Interestingly, in vitro experiments have demonstrated that MAG slows down the progression of liver fibrosis by inhibiting the activation of HSCs, and further confirms that MAG promotes ferroptosis in ROS-mediated activated HSCs. In short, MAG has a good alleviating effect on liver fibrosis and will be a potential candidate drug for the treatment of liver fibrosis.

IntroductionMorphine is a widely used analgesic, but its prolonged use often leads to tolerance, limiting its therapeutic efficacy. Research implicates the NLRP3 inflammasome and reactive astrocytes in the development of morphine tolerance, with reactive astrocytes classified into A1 neurotoxic and A2 neuroprotective phenotypes. This study explores the role of the NLRP3 inflammasome and the transformation of astrocyte phenotypes in the progression of morphine tolerance.MethodsA model of morphine tolerance was established by administering morphine intrathecally for seven consecutive days. To inhibit NLRP3 inflammasome activation, we coadministered MCC950, a selective NLRP3 inhibitor. Thermal withdrawal latency was used to assess tolerance development. Protein and mRNA levels of GFAP, IL-18, NLRP3, C3 (A1 marker), and S100A10 (A2 marker) in the spinal cord were measured using Western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). Immunofluorescence was employed to assess the colocalization of C3 and GFAP.ResultsSeven days of morphine administration induced tolerance, which was associated with increased levels of GFAP, IL-18, NLRP3, and C3, and a decreased level of S100A10. Coadministration of morphine and MCC950 significantly slowed the development of morphine tolerance and reversed changes in NLRP3, IL-18, GFAP, C3, and S100A10 protein levels.DiscussionOur findings indicate a significant link between NLRP3 inflammasome activation and morphine tolerance, suggesting that NLRP3 contributes to the transformation of astrocytes to the A1 phenotype. Inhibiting NLRP3 inflammasome activation holds promise in reversing astrocyte phenotype changes, potentially mitigating morphine tolerance.

BackgroundNon-small cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) alterations poses a substantial treatment challenge. Current HER2-targeted therapies offer limited efficacy. Antibody-drug conjugates (ADCs) targeting HER2 have emerged as a promising therapeutic strategy. This study aimed to evaluate the clinical response to a novel ADC drug Disitamab vedotin (RC48) in advanced NSCLC with HER2 alterations.MethodsThis study conducted a retrospective review of patients harboring HER2 alterations treated with RC48 in the real world. Clinical outcomes were evaluated in terms of objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).ResultsOut of 22 patients, 21 (95.5%) received RC48 combination therapy, while one received RC48 monotherapy. The ORR of all patients reached 45.5%, and the DCR stood at 90.9%. The median PFS (mPFS) was 7.5 months. Among patients receiving RC48 combination therapy, the ORR was 47.7%, and the mPFS of 8.1 months. The combination of RC48 with platinum+/- bevacizumab resulted in the highest ORR of 71.4% (5 out of 7 patients), with HER2 TKI following at a 50.0% ORR (4 out of 8 patients). First-line (1L) treatment with RC48 showed an ORR of 62.5% (5 out of 8 patients), second-line (2L) treatments had a 57.1% ORR (4 out of 7 patients), and beyond second-line (>2L) treatments exhibited a 14.3% ORR (1 out of 7 patients). Patients with 1L, 2L, or >2L treatment had a mPFS of 8.1 months, 7.2 months, and 7.4 months, respectively. Patients with HER2 mutations or amplifications, and those with concurrent mutations and amplifications at baseline, showed mPFS of 8.1 months, 9.4 months, and 7.4 months, respectively. The mPFS was significantly longer in patients with HER2 amplification. The most common adverse events included hand-foot syndrome (54.5%), asthenia (50.0%), decreased white blood cell count (45.5%), and liver impairment (45.5%). Grade 3 adverse events occurred in one (4.5%) patient.ConclusionRC48, particularly in combination regimens, demonstrates promising efficacy in advanced NSCLC with HER2 alterations. These findings underscore the need for further research to validate RC48’s application in clinical practice.

Sample pretreatment is an essential procedure in pesticide analysis, as the matrix effect can significantly influence the results. In this study, a covalent organic framework (COF) was synthesized using 1,2,4,5-tetrakis-(4-formylphenyl)benzene (TFPB) and benzidine (BD) to mitigate the matrix effect in vegetable and fruit samples. This COF was then used to develop a solid-phase extraction (CSPE) method. In addition, the COF was used to create a magnetic COF (MCOF) for use in magnetic solid-phase extraction (MSPE). The synthesized COF and MCOF were thoroughly characterized using scanning electron microscopy (SEM) for morphological analysis, Fourier-transform infrared spectroscopy (FT-IR) for chemical bond identification, and N2 adsorption–desorption measurements for porosity and surface area assessment. Key pretreatment parameters such as buffers, dilution rate, sorbent dosage, extraction time, elution solvent, and reuse number were optimized. The developed CSPE and MSPE showed excellent purification ability for the matrix of vegetable and fruit samples. The reuse test demonstrated that the synthesized COF and MCOF can be reused up to 15 times. Moreover, the developed CSPE and MSPE showed acceptable recoveries in spiked recovery tests, suggesting that these pretreatment methods were feasible for sample purification in pesticide analysis.

ObjectiveThe pathogenesis of antituberculosis drug-induced liver injury (AT-DILI) remains largely unknown. The current investigation aimed to determine the genetic contribution of the nuclear receptor subfamily 1 Group I member 3 (NR1I3) and nuclear receptor subfamily 1 Group H member 4 (NR1H4) genes to the risk of AT-DILI in the Chinese population.MethodsA 1:4 matched case‒control study was conducted, and five single nucleotide polymorphisms (SNPs) in the NR1I3 and NR1H4 genes were detected and assessed. Utilizing a multivariate conditional logistic regression model, the effects of haplotype and genotype on the risk of AT-DILI were examined. Extended subgroup analysis was carried out based on sex. The distribution of the peak value of serum liver enzymes also compared among different genotypes.Results224 AT-DILI cases and 896 controls were included in this study. No significant difference was observed in genotypes or haplotypes frequencies between AT-DILI cases and controls. However, comparisons of liver function indicators revealed significant differences in the peak values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) among patients with different genotypes of NR1H4 rs56163822 (GG vs. GT vs. TT, 27.1 U/L vs. 26.0 U/L vs. 23.0 U/L, p = 0.020; 34.0 U/L vs. 31.0 U/L vs. 30.6 U/L, p = 0.008; 15.5 μmol/L vs. 15.0 μmol/L vs. 13.7 μmol/L, p = 0.029, respectively), as well as in the peak values of ALT and AST among male patients with different genotypes of NR1H4 rs56163822 (29.0 U/L vs. 26.9 U/L vs. 22.6 U/L, p = 0.002; 34.0 U/L vs. 32.0 U/L vs. 30.5 U/L, p = 0.019, respectively).ConclusionBased on this 1:4 individual-matched case‒control study, the SNP rs56163822 in the NR1H4 gene may be linked to the susceptibility to AT-DILI in Chinese patients receiving anti-TB treatment. Further studies in larger varied populations are needed to validate our findings.

PurposeTo assess the potential added value of the lung immune prognostic index (LIPI) in patients with small cell lung cancer (SCLC), treated with programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) inhibitors, who lived in the Chinese alpine region.Methods120 SCLC patients treated with PD-L1/PD-1 inhibitors were divided into three LIPI groups, from July 2018 to April 2021. Cox regression models were used to evaluate the prognostic effect of three LIPI groups on overall survival (OS) and progression-free survival (PFS). Logistic regression analysis was conducted to explore the association between immune-related adverse events (irAEs) and the pretreatment of neutrophil-to-lymphocyte ratio (dNLR), lactate dehydrogenase (LDH), and LIPI.ResultsThe median OS was 4.5, 6.3, and 10.0 months (p=0.001) and the median PFS was 2.5, 4.3, and 5.3 months (p=0.049) for Poor, Intermediate, and Good LIPI, respectively. The disease control rate (DCR) was also higher in the Good LIPI group (p=0.003). Moreover, multivariate analysis confirmed that worse LIPI was correlated with shorter OS and PFS. dNLR was associated with the onset of irAEs, not LIPI. Conclusion: The LIPI might be a promising predictive and prognostic biomarker in SCLC patients treated with PD-L1/PD-1 inhibitors in the Chinese Alpine region.

Abstract Background Intestinal barrier is a dynamic interface between the body and the ingested food components, however, dietary components or xenobiotics could compromise intestinal integrity, causing health risks to the host. Gossypol, a toxic component in cottonseed meal (CSM), caused intestinal injury in fish or other monogastric animals. It has been demonstrated that probiotics administration benefits the intestinal barrier integrity, but the efficacy of probiotics in maintaining intestinal health when the host is exposed to gossypol remains unclear. Here, a strain (YC) affiliated to Pediococcus pentosaceus was isolated from the gut of Nile tilapia (Oreochromis niloticus) and its potential to repair gossypol-induced intestinal damage was evaluated. Results A total of 270 Nile tilapia (2.20 ± 0.02 g) were allotted in 3 groups with 3 tanks each and fed with 3 diets including CON (control diet), GOS (control diet containing 300 mg/kg gossypol) and GP (control diet containing 300 mg/kg gossypol and 108 colony-forming unit (CFU)/g P. pentosaceus YC), respectively. After 10 weeks, addition of P. pentosaceus YC restored growth retardation and intestinal injury induced by gossypol in Nile tilapia. Transcriptome analysis and siRNA interference experiments demonstrated that NOD-like receptors (NLR) family caspase recruitment domain (CARD) domain containing 3 (Nlrc3) inhibition might promote intestinal stem cell (ISC) proliferation, as well as maintaining gut barrier integrity. 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) revealed that addition of P. pentosaceus YC altered the composition of gut microbiota and increased the content of propionate in fish gut. In vitro studies on propionate’s function demonstrated that it suppressed nlrc3 expression and promoted wound healing in Caco-2 cell model. Conclusions The present study reveals that P. pentosaceus YC has the capacity to ameliorate intestinal barrier injury by modulating gut microbiota composition and elevating propionate level. This finding offers a promising strategy for the feed industry to incorporate cottonseed meal into fish feed formulations. Graphical Abstract

Abstract Background Herbal nanoparticles are made from natural herbs/medicinal plants, their extracts, or a combination with other nanoparticle carriers. Compared to traditional herbs, herbal nanoparticles lead to improved bioavailability, enhanced stability, and reduced toxicity. Previous research indicates that herbal medicine nanomaterials are rapidly advancing and making significant progress; however, bibliometric analysis and knowledge mapping for herbal nanoparticles are currently lacking. We performed a bibliometric analysis by retrieving publications related to herbal nanoparticles from the Web of Science Core Collection (WoSCC) database spanning from 2004 to 2023. Data processing was performed using the R package Bibliometrix, VOSviewers, and CiteSpace. Results In total, 1876 articles related to herbal nanoparticles were identified, originating from various countries, with China being the primary contributing country. The number of publications in this field increases annually. Beijing University of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, and Saveetha University in India are prominent research institutions in this domain. The Journal “International Journal of Nanomedicine” has the highest number of publications. The number of authors of these publications reached 8234, with Yan Zhao, Yue Zhang, and Huihua Qu being the most prolific authors and Yan Zhao being the most frequently cited author. “Traditional Chinese medicine,” “drug delivery,” and “green synthesis” are the main research focal points. Themes such as “green synthesis,” “curcumin,” “wound healing,” “drug delivery,” and “carbon dots” may represent emerging research areas. Conclusions Our study findings assist in identifying the latest research frontiers and hot topics, providing valuable references for scholars investigating the role of nanotechnology in herbal medicine. Graphical Abstract

Malignant peritoneal mesothelioma is an exceedingly rare malignant tumor. Herein, we present a case of malignant peritoneal mesothelioma in a 59-year-old Chinese female patient who was stable after treatment for multiple relapses. Imaging revealed massive ascites and an irregular thickening of the peritoneal mesangium. Laparoscopic biopsy revealed heterogeneous cell nests in the parietal peritoneal fibrous tissue, which were confirmed by immunohistochemical staining for Calretinin, WT-1, and D2-40. In terms of genetic screening, BAP1, CSF1R , and other key driver gene variants closely related to malignant peritoneal mesothelioma have been explored in tumor tissues. Notably, CARD11 driver mutation was first found in all malignant peritoneal mesothelioma patients, and ATM A1159T gene mutation found in recurrent focal tissue may be associated with recurrent tumor recurrence.

IntroductionThe potato holds the distinction of being the world’s largest non-cereal food crop and ensuring its sustainable production is imperative for global food security. Notably, China leads in both the planting area and output of potatoes globally, cementing its crucial role in the nation’s agricultural economy. A scientific assessment of the effectiveness of organic fertilizers on potato cultivation can significantly contribute to the promotion of sustainable agriculture.MethodsThis study utilizes a Propensity Score Matching (PSM) model and introduces a novel cost-efficiency approach to analyze and evaluate the production efficiency and economic impact of organic fertilizer application among 546 potato growers in Shandong.ResultsThe research findings reveal the following: Firstly, compared to the control group without organic fertilizer application, it is evident that the use of organic fertilizers enhances production technology efficiency, labor productivity, land productivity, and net profit per unit by 3.6%, 1588.47 kg/person, 16346.77 kg/ha, and 16135.32 yuan/ha, respectively. Secondly, an examination of cost efficiency among growers with different production scales indicates that those with a planting scale of 0.667-1.333 hectares demonstrate relatively high production efficiency across multiple factors. Additionally, there is an observable inverted U-shaped trend in the relationship between planting scale and production efficiency. Thirdly, the continuous application of organic fertilizers proves advantageous in mitigating inefficiencies in investment techniques, leading to cost savings and efficiency improvements in potato cultivation.DiscussionConsequently, it is recommended that the government and relevant departments enhance technical support, elevate professional training programs, and optimize the allocation of input factors. These measures aim to encourage farmers to adopt organic fertilizers, thereby promoting sustainable agricultural practices.

Inhibiting the death receptor 3 (DR3) signaling pathway in group 3 innate lymphoid cells (ILC3s) presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis (UC). Paeoniflorin, a prominent component of Paeonia lactiflora Pall., has demonstrated the ability to restore barrier function in UC mice, but the precise mechanism remains unclear. In this study, we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s. C57BL/6 mice were subjected to random allocation into 7 distinct groups, namely the control group, the 2 % dextran sodium sulfate (DSS) group, the paeoniflorin groups (25, 50, and 100 mg/kg), the anti-tumor necrosis factor-like ligand 1A (anti-TL1A) antibody group, and the IgG group. We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry, respectively. Meanwhile, DR3-overexpressing MNK-3 cells and 2 % DSS-induced Rag1−/− mice were used for verification. The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier. Simultaneously, paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines (Interleukin-17A, Granulocyte-macrophage colony stimulating factor, and Interleukin-22). Alternatively, paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system. We additionally confirmed that paeoniflorin-conditioned medium (CM) restored the expression of tight junctions in Caco-2 cells via coculture. In conclusion, paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner, and its mechanism is associated with the inhibition of the DR3 signaling pathway.

BackgroundHereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant inheritable disease caused by Fumarate hydratase (FH) gene germline mutation. It is speculated that for HRLCC infertility women with multiple uterine leiomyomas, preimplantation genetic testing may help block transmission of mutated FH gene during pregnancy.Case presentationWe present the case of a 26-year-old nulligravida with a history of early-onset uterine leiomyomatosis had a heterozygous nonsense mutation [NM_000143.4 (FH): c.1027C > T(p.Arg343Ter)] in the HRLLC gene. After ovulation induction and in vitro fertilization, preimplantation genetic testing for monogenic disorders (PGT-M) on embryos revealed the absence of the pathogenic allele in two blastomeres. Uterine fibroids were identified before embryo transfer, leading to a submucosal myomectomy and long period of pituitary suppression by Gonadotropin-releasing hormone analog (GnRHa). The patient achieved a healthy live birth after the second cycle of frozen–thawed embryo transfer.ConclusionThis case details the successful treatment of an infertile patient with an HRLLC family history, resulting in a healthy birth through myomectomy and PGT-M selected embryo transplantation. Our literature search indicates the first reported live birth after HRLLC-PGT-M.

For fault diagnosis, it is important to effectively leverage the inherent characteristics of small datasets, but it is rarely considered in many the existing deep learning approaches. To this end, a dual-path network model based on multiple attention mechanisms is proposed in this work. The proposed model enriches the features of small sample by combining one-dimensional (1-D) frequency signals with two-dimensional (2-D) time-frequency images. A 1-D attention mechanism is applied in the 1-D frequency extraction path to focus classification on sensitive frequency information, while an improved global attention mechanism is added to the 2-D feature extraction path, which refines the key features and reduces interference resulting from noise in the image data. Moreover, the stability of the learning process is enhanced through the application of a combinatorial loss function composed of label smoothing regularization and gradient harmonizing mechanism loss functions. Finally, the diagnostic performance of the proposed method is validated using two different public fault diagnosis datasets in comparison with the state-of-the-art methods.

In the global effort to promote green energy policies, understanding and optimizing boiler combustion processes in coal-fired power plants is crucial. During unit start-ups, shutdowns, and load deep peak regulation, significant energy-saving potential can be harnessed in boilers. This paper focuses on a 600MW supercritical coal-fired power unit and presents an improved Least Squares Support Vector Machine (LS-SVM) model with refined initial parameters. By combining the improved LS-SVM with Affinity Propagation (AP) clustering, a combustion efficiency model for boilers is constructed. The experimental results demonstrate that the AP-based improved LS-SVM model not only reduces computational complexity and training time but also enhances predictive accuracy and generalization performance.

Abstract Transposon-associated ribonucleoprotein TnpB is known to be the ancestry endonuclease of diverse Cas12 effector proteins from type-V CRISPR system. Given its small size (408 aa), it is of interest to examine whether engineered TnpB could be used for efficient mammalian genome editing. Here, we showed that the gene editing activity of native TnpB from Deinococcus radiodurans (ISDra2 TnpB) in mouse embryos was already higher than previously identified small-sized Cas12f1. Further stepwise engineering of noncoding RNA (ωRNA or reRNA) component of TnpB significantly elevated the nuclease activity of TnpB. Notably, an optimized TnpB-ωRNA system could be efficiently delivered in vivo with single adeno-associated virus (AAV) and corrected the disease phenotype in a tyrosinaemia mouse model. Thus, the engineered miniature TnpB system represents a new addition to the current genome editing toolbox, with the unique feature of the smallest effector size that facilitate efficient AAV delivery for editing of cells and tissues.

Abstract To explore the association between lipid markers and osteoarthritis (OA). First, the National Health and Nutrition Examination Survey (NHANES) database was used to screen participants with lipid markers, OA and relevant covariates, and logistic regression was used to analyze the association between lipid markers and OA; Then, under the theoretical framework of Mendelian randomization (MR), two-sample MR was performed using GWAS data of lipid markers and OA to explore the causal association between the two, which was analyzed by inverse variance weighting (IVW) method. Heterogeneity test, sensitivity analysis and pleiotropy analysis were also performed. The NHANES database screened a total of 3706 participants, of whom 836 had OA and 2870 did not have OA. When lipid markers were used as continuous variables, multivariate logistic results showed an association between HDL, LDL and OA (HDL, OR (95%):1.01 (1.00, 1.01); LDL, OR (95%):1.00 (0.99, 1.00)). When lipid markers were used as categorical variables, multivariate logistic results showed the fourth quartile result of 0.713 (0.513, 0.992) for LDL relative to the first quartile. In MR study, the results of the IVW method for TG, TL, HDL and LDL showed OR (95% CI) of 1.06 (0.97–1.16), 0.95 (0.85–1.06), 0.94 (0.86–1.02) and 0.89 (0.80–0.998) with P-values of 0.21, 0.37. 013, 0.046. The heterogeneity tests and multiplicity analyses showed P-values greater than 0.05, and sensitivity analyses showed no abnormal single nucleotide polymorphisms. Through NHANES database and MR analyses, LDL was found to be a protective factor for OA, while HDL still needs further study. Our results provide new biomarkers for preventive and therapeutic strategies for OA.

Background: Lung cancer ranks first in both cancer incidence and mortality in China. The emergence of novel treatments for ALK-positive NSCLC led to an improvement in survival and quality of life for patients with advanced ALK mutation-positive non-small cell lung cancer (NSCLC). This study sought to assess the cost-effectiveness of 6 tyrosine kinase inhibitors (TKIs)—crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib—as first-line treatments for ALK-positive NSCLC from the perspective of the Chinese health care system. Methods: A Markov model was developed to estimate the cost-effectiveness of these 6 TKIs. In this model, ALK-positive NSCLC patients were initially simulated to receive 1 of the 6 TKIs as first-line therapy, followed by different TKIs as subsequent treatment and salvage chemotherapy as last-line treatment. Survival data were sourced from the latest published clinical trials. Costs were derived from recent national health insurance negotiations and hospital information systems of selected health care facilities. Utilities for healthy states and adverse events were obtained from the literature. One-way and probabilistic sensitivity analysis as well as scenario analysis was conducted to assess the robustness of the results. Results: Compared to ensartinib, crizotinib, alectinib, ceritinib, brigatinib, and lorlatinib demonstrated incremental quality-adjusted life years (QALYs) of −1.13, 0.39, −0.58, −0.09, and 0.35, respectively. The corresponding incremental costs were $10 677, $33 501, −$6426, $2672, and $24 358. This resulted in ICERs of –$9449/QALY, $85 900/QALY, $11 079/QALY, $29 689/QALY and $69 594/QALY, respectively. Conclusion: Crizotinib was considered to be absolutely dominated by ensartinib. Under a willingness-to-pay threshold of $38 223/QALY, ceritinib and brigatinib were cost-effective compared with ensartinib, while lorlatinib and alectinib were not cost-effective when compared with ensartinib. Overall, brigatinib emerged as the most cost-effective treatment among all the options considered.

Background: Subarachnoid hemorrhage (SAH) is a serious cerebrovascular emergency. The incidence of SAH and hazard ratio of death increase with age. Objective: In this study, we aimed to observe the effects and potential mechanisms of olfactory three needle (OTN) on cognitive impairment, neuronal activity, and neural stem cell differentiation in SAH rats. Methods: Sprague-Dawley (SD) rats were randomly divided into five groups: Sham, SAH group, SAH + Nimodipine (NMP) group, and SAH + OTN group. The rats in the SAH + OTN group received the OTN electroacupuncture treatment. For treatment with recombinant DKK1 (a Wnt/β-catenin inhibitor), mice were injected with DKK1. Results: Our results found that OTN improved cognitive impairment and hippocampal neuron damage in SAH rats. Furthermore, OTN promoted the proliferation of neural stem cells in SAH rats. Mechanistically, OTN activated Wnt/β-catenin signaling in SAH rats, as indicated by the increased expression levels of Wnt1, β-Catenin, LMNB1, and p-GSK-3β. DKK1 reversed the improvement effect of OTN on cognitive impairment and neuronal damage in SAH rats. Meanwhile, DKK1 blocked the promoting effect of OTN on the proliferation of NSCs in SAH rats. Conclusions: OTN electroacupuncture may be an effective therapeutic strategy for SAH.

Potassium (K) is an essential macronutrient for plant growth and development and influences yield and quality of agricultural crops. Maize (Zea mays) is one of the most widely distributed crops worldwide. In China, although maize consumes a large amount of K fertilizer, the K uptake/utilization efficiency (KUE) of maize cultivars is relatively low. Elucidation of KUE mechanisms and development of maize cultivars with higher KUE are needed. Maize KUE is determined by K+ uptake, transport, and remobilization, which depend on a variety of K+ channels and transporters. We review basic information about K+ channels and transporters in maize, their functions and regulation, and the roles of K+ in nitrogen transport, sugar transport, and salt tolerance. We discuss challenges and prospects for maize KUE improvement.

Abstract Objective To date, no direct comparisons have compared the effectiveness of all ALK inhibitors (ALKis) against ALK‐positive non‐small cell lung cancer (NSCLC). The aim of the present study was to investigate the efficacy and safety of ALKis in ALK‐positive NSCLC. Methods The effectiveness of ALKis was evaluated by assessing progression‐free survival (PFS), overall survival (OS), overall response rate (ORR), and PFS with baseline brain metastasis (BM). The serious adverse events (SAEs: Grade ≥ 3) and adverse events (AEs) leading to discontinuation were pooled to evaluate safety. We conducted an indirect treatment comparison between all ALKis by using a Bayesian model. Results Twelve eligible trials including seven treatments were identified. All of the ALKis improved PFS and ORR relative to chemotherapy. Consistent with alectinib, brigatinib, lorlatinib, and ensartinib showed significant differences versus crizotinib and ceritinib. Lorlatinib seemed to prolong PFS compared with alectinib (0.64, 0.37 to 1.07), brigatinib (0.56, 0.3 to 1.05), and ensartinib (0.53, 0.28 to 1.02). No significant difference was found among them in OS except for alectinib versus crizotinib. Moreover, alectinib was significantly more effective than crizotinib (1.54, 1.02 to 2.5) in achieving the best ORR. Subgroup analyses based on BM indicated that PFS was dramatically lengthened by lorlatinib. Compared with other ALKis, alectinib notably reduced the rate of SAEs. There was no striking difference between discontinuation for AEs, except for ceritinib versus crizotinib. The ranking of validity showed that lorlatinib had the longest PFS (98.32%) and PFS with BM (85.84%) and the highest ORR (77.01%). The rank of probabilities showed that alectinib had the potentially best safety in terms of SAEs (97.85%), and ceritinib had less discontinuation (95.45%). Conclusion Alectinib was the first choice for patients with ALK‐positive NSCLC and even for those with BM, whereas lorlatinib was the second choice. Long‐term follow‐up and prospective studies are warranted to compare ALKis and to verify our conclusions directly.

Abstract Introduction Azvudine and nirmatrelvir-ritonavir are more extensively used to treat COVID-19 in China due to their earlier approval by the National Medical Products Administration. However, there has been a scarcity of research directly comparing the clinical outcomes between azvudine and nirmatrelvir-ritonavir till now. We aimed to make a head-to-head comparison of the efficacy and safety of azvudine or nirmatrelvir-ritonavir in hospitalized patients with COVID-19 in China. Methods This retrospective cohort study was conducted using data collected from Tongde Hospital of Zhejiang Province between December 2022 and January 2023. All-cause mortality, risk of progressing to a critical condition, proportion with nucleic-acid negative conversion (P NANC), time to first nucleic-acid negative conversion (T FNANC), length of hospital stay and incidence of adverse events were systematically assessed as outcomes. Multi-model regression analysis, propensity-score-matching analysis, subgroup analysis and several sensitivity analyses were applied to compare these outcomes. Results This study included a total of 1571 hospitalized patients with COVID-19, among whom 272 received nirmatrelvir-ritonavir and 156 received azvudine. We found no significant differences in all-cause mortality (HR 1.41; 95% CI 0.56–3.56; P = 0.471), risk of progressing to critical COVID-19 (HR 1.67; 95% CI 0.78–3.60; P = 0.189), P NANC (HR 0.87; 95% CI 0.69–1.09; P = 0.220), length of stay (β − 0.82; 95% CI − 2.78 to 1.15; P = 0.414) and adverse event rate (3.21% vs. 4.41%, P = 0.538) between the two groups, although azvudine was slightly less effective than nirmatrelvir-ritonavir. Meanwhile, the azvudine group exhibited a significantly longer T FNANC (β 2.53; 95% CI 0.76–4.29; P = 0.005) than the nirmatrelvir-ritonavir group. Results were similar for propensity-score matching and multiple sensitivity analyses. Conclusion Azvudine probably possessed comparable efficacy and safety to nirmatrelvir-ritonavir, although it was less effective than nirmatrelvir-ritonavir for some outcomes. Graphical Abstract

Abstract Background Soybean (Glycine max) meal is one of the important protein sources for fish, but the non-starch polysaccharides (NSP) in soybean meal impair the intestinal barrier function. Here we aimed to investigate whether xylanase can alleviate the adverse effects on the gut barrier induced by soybean meal in Nile tilapia and to explore the possible mechanism. Results Nile tilapia (Oreochromis niloticus) (4.09 ± 0.02 g) were fed with two diets including SM (soybean meal) and SMC (soybean meal + 3,000 U/kg xylanase) for 8 weeks. We characterized the effects of xylanase on the gut barrier, and the transcriptome analysis was performed to investigate the underlying mechanism. Dietary xylanase improved intestinal morphology and decreased the concentration of lipopolysaccharide (LPS) in serum. The results of transcriptome and Western blotting showed that dietary xylanase up-regulated the expression level of mucin2 (MUC2) which may be related to the inhibition of protein kinase RNA-like endoplasmic reticulum kinase (perk)/activating transcription factor 4 (atf4) signaling pathways. Microbiome analysis showed that addition of xylanase in soybean meal altered the intestinal microbiota composition and increased the concentration of butyric acid in the gut. Notably, dietary sodium butyrate was supplemented into the soybean meal diet to feed Nile tilapia, and the data verified that sodium butyrate mirrored the beneficial effects of xylanase. Conclusions Collectively, supplementation of xylanase in soybean meal altered the intestinal microbiota composition and increased the content of butyric acid which can repress the perk/atf4 signaling pathway and increase the expression of muc2 to enhance the gut barrier function of Nile tilapia. The present study reveals the mechanism by which xylanase improves the intestinal barrier, and it also provides a theoretical basis for the application of xylanase in aquaculture.

Serine protease inhibitors (serpins) are the most numerous and widespread multifunctional protease inhibitor superfamily and are expressed by all eukaryotes. Serpin E2 (serpin peptidase inhibitor, clade E, member 2), a member of the serine protease inhibitor superfamily is a potent endogenous thrombin inhibitor, mainly found in the extracellular matrix and platelets, and expressed in numerous organs and secreted by many cell types. The multiple functions of serpin E2 are mainly mediated through regulating urokinase-type plasminogen activator (uPA, also known as PLAU), tissue-type plasminogen activator (tPA, also known as PLAT), and matrix metalloproteinase activity, and include hemostasis, cell adhesion, and promotion of tumor metastasis. The importance serpin E2 is clear from its involvement in numerous physiological and pathological processes. In this review, we summarize the structural characteristics of the Serpin E2 gene and protein, as well as its roles physiology and disease.

Despite the recognized influence of natural factors on groundwater, the impact of human activities remains less explored because of the challenges in measuring such effects. To address this gap, our study proposes an approach that considers carbon emissions as an indicator of human activity intensity and quantifies their impact on groundwater storage. The combination of carbon emission data and groundwater storage data for 17,152 grid cells over 16 years in 4 typical basins shows that they were generally negatively correlated, whereas both agriculture and aviation had positive impacts on groundwater storage. The longest impact from aviation and agriculture can even persist for 7 years. Furthermore, an increase of 1 Yg CO2/km2 per second in emissions from petroleum processing demonstrates the most pronounced loss of groundwater storage in the Yangtze River Basin (approximately 4.1 mm). Moreover, regions characterized by high-quality economic development tend to have favorable conditions for groundwater storage. Overall, our findings revealed the substantial role of human activities in influencing groundwater dynamics from both temporal and spatial aspects. This study fills a crucial gap by exploring the relationship between human activities and groundwater storage through the introduction of a quantitative modeling framework based on carbon emissions. It also provides insights for facilitating empirical groundwater management planning and achieving optimal emission reduction levels.

ObjectiveOur study aimed to visualize the global status and frontiers in stem cell therapy for spinal cord injury by using bibliometric methodology.MethodsPublication citation information related to stem cell therapy for spinal cord injury (SCI) studies between 2003 and 2022 was retrieved from the Web of Science Core Collection database. For the visualized study, VOS viewer software and Graph Pad Prism 9.5 were used to perform bibliometric analysis of included data and publication number statistics in stem cell therapy for the SCI domain.ResultsA total of 6,686 publications were retrieved. The USA and China made the highest contributions to global research with the highest number of citations and link strength. The journal Experimental Neurology ranks as the top journal, combining the publication amount and bibliometrics results. The University of Toronto, based in Canada, was the first-ranking institution. The directions of the current study could be divided into five clusters. The research of Transplantation and Regenerative Medicine and Neurosciences Mechanism Research may be the emerging frontiers in this domain.ConclusionIn summary, stem cell therapy for spinal cord injuries is poised for more valuable advances.

Abstract Mitochondrial base editing with DddA‐derived cytosine base editor (DdCBE) is limited in the accessible target sequences and modest activity. Here, the optimized DdCBE tools is presented with improved editing activity and expanded C‐to‐T targeting scope by fusing DddA11 variant with different cytosine deaminases with single‐strand DNA activity. Compared to previous DdCBE based on DddA11 variant alone, fusion of the activation‐induced cytidine deaminase (AID) from Xenopus laevis not only permits cytosine editing of 5′‐GC‐3′ sequence, but also elevates editing efficiency at 5′‐TC‐3′, 5′‐CC‐3′, and 5′‐GC‐3′ targets by up to 25‐, 10‐, and 6‐fold, respectively. Furthermore, the A‐to‐G editing efficiency is significantly improved by fusing the evolved DddA6 variant with TALE‐linked deoxyadenosine deaminase (TALED). Notably, the authors introduce the reported high‐fidelity mutations in DddA and add nuclear export signal (NES) sequences in DdCBE and TALED to reduce off‐target editing in the nuclear and mitochondrial genome while improving on‐target editing efficiency in mitochondrial DNA (mtDNA). Finally, these engineered mitochondrial base editors are shown to be efficient in installing mtDNA mutations in human cells or mouse embryos for disease modeling. Collectively, the study shows broad implications for the basic study and therapeutic applications of optimized DdCBE and TALED.

Liver cancer is a huge global challenge. It has been exacerbated by tumor-associated dendritic cells (TDCs) due to Endoplasmic Reticulum (ER) stress. We planned to investigate the effects of LBP3 on TDCs immune function, and to explore whether the underlying mechanism was associated with IRE1α-XBP1 pathway of ER stress regulating lipid metabolism. In our early studies, LBP3 (40–350 kDa) with significant anti-tumor and immunomodulatory activities was isolated from the polysaccharide of Lycium barbarum L. (LBP). Here, we determined that LBP3 had a great anti-tumor efficacy in H22-tumor bearing mice by functional activation of TDCs. In vivo and in vitro results showed that LBP3 could up-regulate the expression of MHC Ⅱ, CD80 and CD86 on TDCs, increase the level of TNF-α secreted by TDCs, enhance TDCs’ ability to improve the proliferation and immunosuppression of lymphocytes. Furthermore, LBP3 could decrease the high expression of ER stress-related proteins IRE1α, GRP78, XBP1 and CHOP, reduce the lipid accumulation, raise the low expression of costimulatory molecules on TDCs induced by thapsigargin (TG). Taken together, LBP3 could reduce intracellular lipid accumulation by inhibiting IRE1α-XBP1 pathway of ER stress, improve the function of TDCs to stimulate T cells, thence play an anti-tumor role.

Peritoneal effusion is a common event in ovarian cancer (OC) patients. LncRNA H19 and vascular endothelial growth factor (VEGF) are implicated in cancer progression. The study evaluated the curative effect and safety of bevacizumab combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in OC patients with peritoneal effusion and the effect on serum lncRNA H19/VEGF levels. Totally 248 OC patients with peritoneal effusion were treated with intraperitoneal bevacizumab + HIPEC (observation group) or abdominal paracentesis without HIPEC (control group). The clinical efficacy, quality of life, and adverse reactions were evaluated after two treatment cycles. The serum lncRNA H19 and VEGF levels pre-/post-treatment were determined by RT-qPCR and ELISA. The observation group exhibited better clinical efficacy than the control group, evidenced by a higher partial response rate, response rate, and disease control rate. The observation group exhibited reduced physical/cognitive/role/social/emotional function scores and total adverse reactions. LncRNA H19/VEGF levels showed no significant difference between the two groups before treatment but were significantly downregulated in the observation group after treatment. Summarily, intraperitoneal bevacizumab + HIPEC has significant efficacy in treating peritoneal effusion, improves the quality of life, and reduces serum lncRNA H19 and VEGF levels in OC patients, with fewer adverse reactions and higher safety.Impact statement What is already known on this subject? The utilization of hyperthermic intraperitoneal chemotherapy (HIPEC) as an emerging treatment option for abdominal malignancies has garnered the attention of numerous researchers over the years, which has significant clinical effects on peritoneal effusion in ovarian cancer and can control patients’ conditions and improve their signs and symptoms to a certain extent. What do the results of this study add? In this paper, we investigated the efficacy and safety of intraperitoneal bevacizumab combined with hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal effusion in ovarian cancer. Meanwhile, we compared serum lncRNA H19 and VEGF levels before and after treatment. What are the implications of these findings for clinical practice and/or further research? Our findings may provide a clinically worthy method for the treatment of peritoneal effusion in ovarian cancer. The treatment method reduces serum lncRNA H19 and VEGF levels in patients, which provides a theoretical basis for further research.

AbstractBackground Trimethylamine N-oxide (TMAO) derived from gut microbiota causes kidney-heart damage in chronic kidney disease (CKD) patients. However, it is controversial whether CKD patients with higher TMAO are associated with a higher risk of death. We aimed to assess the correlation between circulating TMAO concentration and the risk of all-cause and cardiovascular death in CKD patients of different dialysis statuses and different races by dose-response analyses, and the underlying mechanisms were also explored by analyzing the correlations of TMAO with glomerular filtration rate (GFR) and inflammation.Method PubMed, Web of Science, and EMBASE were systematically searched up to 1 July 2022. A total of 21 studies involving 15,637 individuals were included. Stata 15.0 was used to perform the meta-analyses and dose-response analyses with extracted data. Subgroup analyses were conducted to recognize possible sources of heterogeneity.Results The risk of all-cause mortality was increased in non-dialysis CKD patients (RR = 1.26, 95%CI = 1.03–1.54, p = 0.028) and non-black dialysis patients (RR = 1.62, 95%CI = 1.19–2.22, p = 0.002) with the highest circulating TMAO concentration, and the association was confirmed to be linear. In addition, an increased risk of cardiovascular mortality was also found in non-black dialysis patients with the highest circulating TMAO concentration (RR = 1.72, 95%CI = 1.19–2.47, p = 0.004), likewise, a linear association was identified. However, for dialysis patients including blacks with high TMAO concentrations, there was no significant increase in either all-cause mortality (RR = 0.98, 95%CI = 0.94-1.03, p = 0.542) or cardiovascular mortality (RR = 0.87, 95% CI = 0.65–1.17, p = 0.362). Meanwhile, we verified strong correlations between TMAO and both GFR (r= −0.49; 95% CI= −0.75, −0.24; p

Abstract Background As the rate of multiple pregnancies increases, delayed interval delivery (DID) is increasingly being implemented to improve perinatal outcomes. But there are no international guidelines for DID in multiple pregnancies. We report a case of DID in a quadruplet pregnancy and review the relevant literature to summarize the management of DID in multiple pregnancies. Case presentation A 22-year-old woman, 22 2/7 weeks' gestation, with quadruplets, was admitted to the hospital for a first cervical cerclage due to cervical dilation. Twenty-five days later, it was found that the cervix was dilated again, so after removing the cervical cerclage, the first quadruplet was delivered vaginally (25 6/7 weeks), and a second cervical cerclage was performed. Four days later, due to re-dilation of the cervix, after removal of the cervical cerclage, the second quadruplet was delivered vaginally (26 3/7 weeks), followed by a third cervical cerclage. Six days later, the pregnancy was terminated by cesarean section due to fetal distress, and the third and fourth quadruplets were delivered (27 2/7 weeks). The patient had no postoperative complications, and all four infants were treated in the neonatal intensive care unit and discharged successfully. Conclusion This case emphasizes that comprehensive management of delayed interval delivery can improve perinatal outcomes in multiple pregnancies, including anti-infection, tocolytic therapy, practice to promote fetal lung, and cervical cerclage.

Crop residue decomposition is an important part of the carbon cycle in agricultural ecosystems, and microorganisms are widely recognized as key drivers during this process. However, we still know little about how nitrogen (N) input and rhizosphere effects from the next planting season impact key straw-decomposing microbial communities. Here, we combined amplicon sequencing and DNA-Stable Isotope Probing (DNA-SIP) to explore these effects through a time-series wheat pot experiment with four treatments: 13C-labeled maize straw addition with or without N application (S1N1 and S1N0), and no straw addition with or without N application (S0N1 and S0N0). The results showed that straw addition significantly reduced soil microbial alpha diversity in the early stages. Straw addition changed microbial beta diversity and increased absolute abundance in all stages. Growing plants in straw-amended soil further reduced bacterial alpha diversity, weakened straw-induced changes in beta diversity, and reduced bacterial and fungal absolute abundance in later stages. In contrast, N application could only increase the absolute abundance of soil bacteria and fungi while having little effect on alpha and beta diversity. The SIP-based taxonomic analysis of key straw-decomposing bacteria further indicated that the dominant phyla were Actinobacteria and Proteobacteria, with overrepresented genera belonging to Vicinamibacteraceae and Streptomyces. Key straw-decomposing fungi were dominated by Ascomycota, with overrepresented genera belonging to Penicillium and Aspergillus. N application significantly increased the absolute abundance of key straw-decomposing microorganisms; however, this increase was reduced by the rhizosphere effect. Overall, our study identified key straw-decomposing microorganisms in straw-amended soil and demonstrated that they exhibited opposite responses to N application and the rhizosphere effect.

Abstract Background Acute kidney injury (AKI) refers to a tricky clinical disease, known by its high morbidity and mortality, with no real specific medicine for AKI. The carbonization product from Pollen Typhae (i.e., Pu-huang in China) has been extensively employed in clinic, and it is capable of relieving the renal damage and other diseases in China since acient times. Results Inspired by the carbonization process of Traditional Chinese Medicine (TCM), a novel species of carbon dots derived from Pollen Typhae (PT-CDs) was separated and then collected using a one-pot pyrolysis method. The as-prepared PT-CDs (4.85 ± 2.06 nm) with negative charge and abundant oxygenated groups exhibited high solubility, and they were stable in water. Moreover, the rhabdomyolysis (RM)-induced AKI rat model was used, and it was first demonstrated that PT-CDs had significant activity in improving the level of BUN and CRE, urine volume and kidney index, and histopathological morphology in RM-induced AKI rats. It is noteworthy that interventions of PT-CDs significantly reduced degree of inflammatory reaction and oxidative stress, which may be correlated with the basial potential mechanism of anti-AKI activities. Furthermore, cytotoxicity assay and biosafety evaluation exhibited high biocompatibility of PT-CDs. Conclusion This study offers a novel relieving strategy for AKI based on PT-CDs and suggests its potential to be a related candidate for clinical applications. Graphical Abstract

As one of the most important fruit tree crops, apple (Malus ×domestica), is faced with the serious impact of soil salinization. However, the underlying genetic and regulatory network remains elusive. Here, we adopted time-course RNA sequencing to decipher the genetic basis and regulatory module of apple in response to salt stress. Among a series of intense changes in genes at each time point, the critical genes in the mitogen-activated protein kinase signaling pathway were highly consistent with the duration of the stress treatment. Moreover, Salt Overly Sensitive 1 (SOS1) genes were identified and predicted to play important roles in the response process. We constructed coexpression modules and explored modules significantly associated with stress. SOS genes were identified in the hub genes, suggesting a critical role. Interestingly, transcription factors were also identified and predicted to cointeract with SOS genes in the hub genes of the coexpression module [e.g., HB7 (MD01G1226600), WRKY33 (MD12G1181000), and ERF106 (MD07G1248700)]. Collectively, our exploration and findings provide a reference and data resource for the study of genetic and salt regulatory networks in apple.

This paper experimentally investigates the perform-ance of free-space optical (FSO) communication based on mode diversity reception (MDR) using nonmode selective photonic lantern (NSPL) and equal gain combining (EGC). By employing a mode demultiplexer and combining technology in the receiver, the bit error rate (BER) and outage performance of FSO communication system can be significantly improved. However, different from diversity system with multiple receive apertures, the branches in mode diversity system are non-independent fading signals, which are influenced by not only atmospheric but also the modal crosstalk of mode demultiplexer. Therefore, we take into consideration the difference of mode demultiplexer and study four schemes for FSO mode diversity reception system: 1) NSPL with equal gain combining (NSPL-EGC), 2) NSPL with maximal ratio combining (NSPL-MRC), 3) mode selective photonic lantern with equal gain combining (MSPL-EGC), and 4) mode selective photonic lantern with equal gain combining (MSPL-MRC). Experimental results show that NSPL-EGC is the most suitable scheme for MDR with low implementation complexity, and the performance difference is less than 1 dB compared with the one using MRC at BER = 3.8×10−3 under turbulence from weak to strong.

The Omicron variants spread rapidly worldwide after being initially detected in South Africa in November 2021. It showed increased transmissibility and immune evasion with far more amino acid mutations in the spike (S) protein than the previously circulating variants of concern (VOCs). Notably, on 15 July 2022, we monitored the first VOC / Omicron subvariant BA.2.75 in China from an imported case. Moreover, nowadays, this subvariant still is predominant in India. It has nine additional mutations in the S protein compared to BA.2, three of which (W152R, G446S, and R493Q reversion) might contribute to higher transmissibility and immune escape. This subvariant could cause wider spread and pose a threat to the global situation. Our timely reporting and continuous genomic analysis are essential to fully elucidate the characteristics of the subvariant BA.2.75 in the future.

Pyruvate dehydrogenase kinases (PDKs)-pyruvate dehydrogenase E1α subunit (PDHE1α) axis plays an important role in regulating glucose metabolism in mammals. However, the regulatory function of PDKs-PDHE1α axis in the glucose metabolism of fish is not well known. This study determined whether PDKs inhibition could enhance PDHE1α activity, and improve glucose catabolism in fish. Nile tilapia fingerlings (1.90 ± 0.11 g) were randomly divided into 4 treatments in triplicate (30 fish each) and fed control diet without dichloroacetate (DCA) (38% protein, 7% lipid and 45% corn starch) and the control diet supplemented with DCA, which inhibits PDKs through binding the allosteric sites, at 3.75 (DCA3.75), 7.50 (DCA7.50) and 11.25 g/kg (DCA11.25), for 6 wk. The results showed that DCA3.75, DCA7.50 and DCA11.25 significantly increased weight gain, carcass ratio and protein efficiency ratio (P

There is a need for sustainable ways of processing plant fibers. Most chemical degumming methods pose a threat to the eco-system because of the presence of toxins during disposal. This study aimed to find sustainable ways of processing banana fiber with less harm to the environment. Sodium hydroxide (NaOH) and activated water were utilized for degumming and softening of the banana fiber. Activated water is an aqueous solution of electrolyte with strongly oxidizing active substances prepared by an electrochemical method. The alkali-pretreated banana fiber were immersed in activated water to refine banana fiber. The results from the study show that activated water further refined the fibers down to 39.7 µm diameter after NaOH pretreatment and also achieved better whiteness at 74.7%. The electrochemically activated water solutions displayed a promising effect in removing lignin, hemicellulose, and other impurities. The fibers of this quality could be used in the spinning of yarn and for other textile applications. Various analytical techniques, including digital microscope, scanning electron microscope, Fourier transform Infrared spectroscopy, X-ray diffractometry, tensile test, and whiteness test were utilized. These tests confirmed that the activated water used on banana fiber enhanced physical, chemical, and morphological properties.

This study focused on reducing the burden of air pollution, wastage of banana pseudostems, and adding value to the plant’s products. Alkali pre-treatment and ultrasounds aided in degumming banana fiber to remove wax, lignin, hemicellulose, and other unwanted extractives. The chemical analysis method revealed 72.78% cellulosic content in ultra-sonicated fiber. Ultra-sonication attained an average diameter of 19.36 μm compared to 49.94 μm of alkali pre-treated fiber and 171.87 μm of untreated fiber as observed through the digital optical microscope. Scanning Electron Microscopy (SEM) showed well-separated fibrils of ultra-sonicated fiber. X-Ray Photoelectron Spectroscopy (XPS) showed de-convoluted peaks of C1s, O1s, and N1s that confirmed lignin removal. Transform Infra-Red (ATR-FTIR) Spectrometer revealed varnishing peak bands of C − O and C═O functional groups between 1600 cm−1 and 1733 cm−1 related to lignin and hemicelluloses. The X-ray Diffractometer (XRD) showed improved crystallinity up to 63.29%. The single fiber strength testing machine showed optimized breaking strength of 31.12cN/dtex and breakage elongation of 9.38%. The chemical, mechanical and morphological properties showed great promise for high-quality banana fibers.

Abstract Work alienation refers to mental self-separation from work, and it is an integral reflection of workers and their work. Few studies have explored the association between work area and work alienation among grassroots judicial administrators. A stratified sampling method was used to collect data from 288 grassroots judicial administrators in Guangzhou to measure the overall status quo and work alienation in this group. This study found that the current grassroots judicial administrative team has a reasonable structure, high professional quality, and rich grassroots work experience, but a high level of work intensity (Mean = .667) and a lack of autonomy (Mean = .757) are prominent. Work area (unstandardized regression coefficient, B = .917) is significantly related to work alienation when controlling for sociodemographic and work characteristic variables: the closer the work area is to the city centre areas, the higher the level of work alienation. In addition, education level also has a significant effect on work alienation: the lower the individual education level is, the stronger the work alienation. The discussion focuses on the knowledge needs in grassroots judicial administrative work and the importance of the external working environment, and further research implications are proposed.

As the charcoal processing product of Scutellariae Radix (SR), SR Carbonisata (SRC) has been clinically used as a cooling blood and hemostatic agent for thousands of years. However, the underlying active ingredients and mechanism of SRC still remained unspecified. In this study, SRC derived carbon dots (SRC-CDs) were extracted and purified from the aqueous solution of SRC, followed by physicochemical property assessment by series of technologies. The cooling blood and hemostatic effects of SRC-CDs were further evaluated via a blood-heat and hemorrhage (BHH) rat model. Results showed that the diameters of obtained fluorescent SRC-CDs ranged from 5.0 nm to 10.0 nm and possessed functional group-rich surfaces. Additionally, the as-prepared SRC-CDs showed remarkable cooling blood and hemostasis effects in BHH model, mainly manifested by significant improvement of elevated rectal temperature, inflammatory cytokines (TNF-α, IL-6, and IL-1β) levels, as well as protein expressions of myD88 and NF-κB p65, abnormal coagulation parameters (elevated APTT and FIB), hemogram parameters (RBC, HGB, and HCT), and histopathological changes in lung and gastric tissues. This study, for the first time, demonstrated that SRC-CDs were the cooling blood and hemostatic active components of SRC, which could inhibit the release of inflammatory cytokines by regulating myD88/NF-κB signaling pathway, and activating the fibrin system and endogenous coagulation pathway. These results not only provide a new perspective for the study of active ingredients of carbonized herbs represented by SRC, but also lay an experimental foundation for the development of next-generation nanomedicines.

BackgroundPain is one of the most common and troublesome symptoms of cancer. Although potential positive effects of acupuncture-point stimulation (APS) on cancer pain have been observed, knowledge regarding the selection of the optimal APS remains unclear because of a lack of evidence from head-to-head randomized controlled trials (RCTs).ObjectiveThis study aimed to carry out a network meta-analysis to compare the efficacy and safety of different APS combined with opioids in treating moderate to severe cancer pain and rank these methods for practical consideration.MethodsA comprehensive search of eight electronic databases was conducted to obtain RCTs involving different APS combined with opioids for moderate to severe cancer pain. Data were screened and extracted independently using predesigned forms. The quality of RCTs was appraised with the Cochrane Collaboration risk-of-bias tool. The primary outcome was the total pain relief rate. Secondary outcomes were the total incidence of adverse reactions, the incidence of nausea and vomiting, and the incidence of constipation. We applied a frequentist, fixed-effect network meta-analysis model to pool effect sizes across trials using rate ratios (RR) with their 95% confidence intervals (CI). Network meta-analysis was performed using Stata/SE 16.0.ResultsWe included 48 RCTs, which consisted of 4,026 patients, and investigated nine interventions. A network meta-analysis showed that a combination of APS and opioids was superior in relieving moderate to severe cancer pain and reducing the incidence of adverse reactions such as nausea, vomiting, and constipation compared to opioids alone. The ranking of total pain relief rates was as follows: fire needle (surface under the cumulative ranking curve (SUCRA) = 91.1%), body acupuncture (SUCRA = 85.0%), point embedding (SUCRA = 67.7%), auricular acupuncture (SUCRA = 53.8%), moxibustion (SUCRA = 41.9%), transcutaneous electrical acupoint stimulation (TEAS) (SUCRA = 39.0%), electroacupuncture (SUCRA = 37.4%), and wrist–ankle acupuncture (SUCRA = 34.1%). The ranking of total incidence of adverse reactions was as follows: auricular acupuncture (SUCRA = 23.3%), electroacupuncture (SUCRA = 25.1%), fire needle (SUCRA = 27.2%), point embedding (SUCRA = 42.6%), moxibustion (SUCRA = 48.2%), body acupuncture (SUCRA = 49.8%), wrist–ankle acupuncture (SUCRA = 57.8%), TEAS (SUCRA = 76.3%), and opioids alone (SUCRA = 99.7%).ConclusionsAPS seemed to be effective in relieving cancer pain and reducing opioid-related adverse reactions. Fire needle combined with opioids may be a promising intervention to reduce moderate to severe cancer pain as well as reduce opioid-related adverse reactions. However, the evidence was not conclusive. More high-quality trials investigating the stability of evidence levels of different interventions on cancer pain must be conducted.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42022362054.