Synthetic lumbar MRI can aid in diagnosis and treatment strategies based on self-pix networks.

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 < 0.001), and SSIM1 and SSIM2 were 0.766 and 0.771 (p < 0.001), respectively. In the ROI group, PSNR1 and PSNR2 were 12.350 and 12.670 (p = 0.004), and SSIM1 and SSIM2 were 0.816 and 0.832 (p = 0.005), respectively. According to the qualitative evaluation, Self-pix-generated MRI showed no significant difference from real MRI in identifying acute fractures (p = 0.689), with a good sensitivity of 84.36% and specificity of 96.65%. No difference in treatment strategy was found between the Self-pix-generated MRI group and the real MRI group (p = 0.135). In this study, a disease-specific GAN named Self-pix was developed, which demonstrated better image generation performance compared to traditional GAN. The spine surgeon could accurately diagnose LF and select treatment strategies based on Self-pix-generated T2 MR images.

Case report: ATM A1159T mutation in malignant peritoneal mesothelioma may be associated with tumor recurrence.

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.

Mechanisms of minor pole-mediated spindle bipolarization in human oocytes.

Spindle bipolarization, the process of a microtubule mass transforming into a bipolar spindle, is a prerequisite for accurate chromosome segregation. In contrast to mitotic cells, the process and mechanism of spindle bipolarization in human oocytes remains unclear. Using high-resolution imaging in more than 1800 human oocytes, we revealed a typical state of multipolar intermediates that form during spindle bipolarization and elucidated the mechanism underlying this process. We found that the minor poles formed in multiple kinetochore clusters contribute to the generation of multipolar intermediates. We further determined the essential roles of HAUS6, KIF11, and KIF18A in spindle bipolarization and identified mutations in these genes in infertile patients characterized by oocyte or embryo defects. These results provide insights into the physiological and pathological mechanisms of spindle bipolarization in human oocytes.

Fish gut-derived probiotic Pediococcus pentosaceus alleviates gossypol-induced intestinal inflammation by inhibiting NLRC3/NF-κB/IL-1ß signal pathway in Nile tilapia.

Cottonseed meal (CSM) and cottonseed protein concentrate (CPC) serve as protein alternatives to fish meal and soybean meal in the feed industry. However, the presence of gossypol residue in CSM and CPC can potentially trigger severe intestinal inflammation, thereby restricting the widespread utilization of these two protein sources. Probiotics are widely used to prevent or alleviate intestinal inflammation, but their efficacy in protecting fish against gossypol-induced enteritis remains uncertain. Here, the protective effect of Pediococcus pentosaceus, a strain isolated from the gut of Nile tilapia (Oreochromis niloticus), was evaluated. Three diets, control diet (CON), gossypol diet (GOS) and GOS supplemented with P. pentosaceus YC diet (GP), were used to feed Nile tilapia for 10 weeks. After the feeding trial, P. pentosaceus YC reduced the activity of myeloperoxidase (MPO) in the proximal intestine (PI) and distal intestine (DI). Following a 7-day exposure to Aeromonas hydrophila, the addition of P. pentosaceus YC was found to increase the survival rate of the fish. P. pentosaceus YC significantly inhibited the oxidative stress caused by gossypol, which was evidenced by lower reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in PI and DI. Addition of P. pentosaceus YC significantly inhibited enteritis, with the lower expression of pro-inflammatory cytokines (il-1ß, il-6, il-8) and higher expression of anti-inflammatory cytokines tgf-ß. RNA-seq analysis indicated that P. pentosaceus YC supplementation significantly inhibited nlrc3 and promoted nf-κb expression in PI and DI, and the siRNA interference experiment in vivo demonstrated that intestinal inflammation was mediated by NLRC3/NF-κB/IL-1ß signaling pathway. Fecal bacteria transplantation experiment demonstrated that gut microbiota mediated the protective effect of P. pentosaceus YC. These findings offer valuable insights into the application of P. pentosaceus YC for alleviating gossypol-induced intestinal inflammation in fish.

Nanozyme-based colorimetric sensor arrays coupling with smartphone for discrimination and "segmentation-extraction-regression" deep learning assisted quantification of flavonoids.

Achieving rapid, cost effective, and intelligent identification and quantification of flavonoids is challenging. For fast and uncomplicated flavonoid determination, a sensing platform of smartphone-coupled colorimetric sensor arrays (electronic noses) was developed, relying on the differential competitive inhibition of hesperidin, nobiletin, and tangeretin on the oxidation reactions of nanozymes with a 3,3',5,5'-tetramethylbenzidine substrate. First, density functional theory calculations predicted the enhanced peroxidase-like activities of CeO2 nanozymes after doping with Mn, Co, and Fe, which was then confirmed by experiments. The self-designed mobile application, Quick Viewer, enabled a rapid evaluation of the red, green, and blue values of colorimetric images using a multi-hole parallel acquisition strategy. The sensor array based on three channels of CeMn, CeFe, and CeCo was able to discriminate between different flavonoids from various categories, concentrations, mixtures, and the various storage durations of flavonoid-rich Citri Reticulatae Pericarpium through a linear discriminant analysis. Furthermore, the integration of a "segmentation-extraction-regression" deep learning algorithm enabled single-hole images to be obtained by segmenting from a 3 × 4 sensing array to augment the featured information of array images. The MobileNetV3-small neural network was trained on 37,488 single-well images and achieved an excellent predictive capability for flavonoid concentrations (R2 = 0.97). Finally, MobileNetV3-small was integrated into a smartphone as an application (Intelligent Analysis Master), to achieve the one-click output of three concentrations. This study developed an innovative approach for the qualitative and simultaneous multi-ingredient quantitative analysis of flavonoids.

Screening and molecular docking verification of feature genes related to phospholipid metabolism in hepatocarcinoma caused by hepatitis B.

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.

Transcriptomic analysis provides insights into the immune responsive genes in the Procambarus clarkii hepatopancreas challenged with Vibrio parahaemolyticus.

Procambarus clarkii is an economically important species in China; however, its high mortality rate due to pathogenic bacteria, particularly Vibrio parahaemolyticus, results in significant economic loss. This study aimed to understand the immune response of crayfish to bacterial infection by comparing and analyzing transcriptome data of hepatopancreatic tissue from P. clarkii challenged with V. parahaemolyticus or treated with PBS. Physiological indices (TP, Alb, ACP, and AKP) were analyzed, and tissue sections were prepared. After assembling and annotating the data, 18,756 unigenes were identified. A comparison of the expression levels of these unigenes between the control and V. parahaemolyticus groups revealed 4037 DEGs, with 2278 unigenes upregulated and 1759 downregulated in the V. parahaemolyticus group. GO (Gene Ontology) enrichment analysis shows that the DGEs are mainly enriched in cellular anatomical activity, bindinga and cellular process, enrichment analysis of KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways showed that DGEs were mainly enriched in Base excision repair, Phagosome and Longevity regulating pathway. At the same time, lysosome was also enriched. The phagosome and lysosome pathways play a crucial role in the immune defense of crayfish against V. parahaemolyticus injection that will be highlighted. In addition, the expression levels of six selected immune-related DEGs were measured using qRT-PCR, which validated the results of RNA-seq analysis. This study provides a new perspective on the immune system and defense mechanisms of P. clarkii and a valuable foundation for further investigation of the molecular immune mechanisms of this species.

Differentially expressed microRNA in prognosis of gastric cancer with Lauren classification.

BACKGROUND: Gastric cancer (GC) is one of the most common tumors. There were several classifications of GC recently. The value of Lauren classification in evaluating the prognosis after radical gastrectomy was still unclear and the prognosis of gastric cancer remained relatively poor in the absence of prognostic biomarkers. This study aimed to explore microRNA (miRNA) in the prognosis of GC with different Lauren classification. METHODS: A retrospective study of 1144 patients was performed in this study. Quantificational reverse transcription-PCR (qRT-PCR) was used to examine the expression of miRNAs. Univariate and multivariate analysis were performed to evaluate prognosis value of Lauren classification. RESULTS: Total 1144 GC patients were recruited in this cohort, including 302 diffuse type (26.4%), 436 intestinal type (38.1%) and 406 mixed type (35.5%) GC. Multivariate analysis showed that Lauren classification, patients' age, tumor size, tumor infiltrating depth, vascular nerve infiltrating and metastatic lymph nodes ration were significantly correlated with GC patients' OS and DFS. The miR-141-3p, miR-200b-3p and miR-133a-5p were significantly down-regulated in diffuse type compared to intestinal type GC tissues, the miR-105-5p had significant lower expression in diffuse type compared with intestinal type and mixed type GC tissues. As a consequence of univariate analysis, low miR-141-3p in diffuse type GC showed significant worse OS and DFS than high miR-141-3p. CONCLUSIONS: Lauren classification was an independent prognostic factor in GC. MiR-141-3p was an independent prognostic factor and a promising prognostic biomarker in Lauren classification GC.

Identification and functional characterization of a long-type peptidoglycan recognition protein, PGRP-L in amphibian Xenopus laevis.

Peptidoglycan recognition proteins (PGRPs) are a family of multifunctional proteins playing vital roles in PGN metabolism and antibacterial defense, and their functions have been well-characterized in mammals, bony fishes, and insects. However, the information about the functions of amphibian long-type PGRP is rather limited. Here, we identified and cloned a long-type PGRP gene (named Xl-PGRP-L) from African clawed frog, Xenopus laevis. Xl-PGRP-L gene was detected in all orangs/tissues examined, and was rapidly induced in intestine, liver, and lung following the stimulation of PGN. Sequence analysis showed that Xl-PGRP-L possesses four Zn2+-binding residues (His358, Tyr395, His470, and Cys478) required for amidase activity of catalytic PGRPs, and assays for amidase activity revealed that recombinant Xl-PGRP-L cloud degrade PGN in a Zn2+-dependent manner, indicating that Xl-PGRP-L is belonging to catalytic PGRPs. In addition, Xl-PGRP-L have antibacterial activity against Gram-negative bacteria Edwardsiella tarda and Gram-positive bacteria Streptococcus agalactiae. The present investigation represents the first characterization regarding the biological activities of amphibian long-type PGRPs, thus contributes to a better understanding of the functions of tetrapod PGRPs and the molecular mechanisms of amphibian antibacterial defense.

The impact of different grazing intensity and management measures on soil organic carbon density in Zhangye grassland.

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.

Rash caused by lurasidone in old chinese patient with bipolar disorder: case-based review.

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.

Synergistic enhancement of cadmium immobilization and soil fertility through biochar and artificial humic acid-assisted microbial-induced calcium carbonate precipitation.

Microbially induced carbonate precipitation (MICP) is emerging as a favorable alternative to traditional soil remediation techniques for heavy metals, primarily due to its environmental friendliness. However, a significant challenge in using MICP for farmland is not only to immobilize heavy metals but also to concurrently enhance soil fertility. This study explores the innovative combination of artificial humic acid (A-HA), biochar (BC), and Sporosarcina pasteurii (S. pasteurii) to mitigate the bioavailability of cadmium (Cd) in contaminated agricultural soils through MICP. X-ray diffraction (XRD) and scanning electron microscope (SEM) analyses revealed that the integration of BC and A-HA significantly enhances Cd immobilization efficiency by co-precipitating with CaCO3. Moreover, this treatment also improved soil fertility and ecological functions, as evidenced by increases in total nitrogen (TN, 9.0-78.2 %), alkaline hydrolysis nitrogen (AN, 259.7-635.5 %), soil organic matter (SOM, 18.1-27.9 %), total organic carbon (TOC, 43.8-48.8 %), dissolved organic carbon (DOC, 36.0-88.4 %) and available potassium (AK, 176.2-193.3 %). Additionally, the relative abundance of dominant phyla such as Proteobacteria and Firmicutes significantly increased with the introduction of BC and A-HA in MICP. Consequently, the integration of BC and A-HA with MICP offers a promising solution for remediating Cd-contaminated agricultural soil and synergistically enhancing soil fertility.

Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells.

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.

Inhibition of mitochondrial citrate shuttle alleviates metabolic syndromes induced by high-fat diet.

The mitochondrial citrate shuttle, which relies on the solute carrier family 25 member 1 (SLC25A1), plays a pivotal role in transporting citrate from the mitochondria to the cytoplasm. This shuttle supports glycolysis, lipid biosynthesis, and protein acetylation. Previous research has primarily focused on Slc25a1 in pathological models, particularly high-fat diet (HFD)-induced obesity. However, the impact of Slc25a1 inhibition on nutrient metabolism under HFD remains unclear. To address this gap, we used zebrafish (Danio rerio) and Nile tilapia (Oreochromis niloticus) to evaluate the effects of inhibiting Slc25a1. In zebrafish, we administered Slc25a1-specific inhibitors (CTPI-2) for four weeks, while Nile tilapia received intraperitoneal injections of dsRNA to knockdown slc25a1b for seven days. Inhibition of the mitochondrial citrate shuttle effectively protected zebrafish from HFD-induced obesity, hepatic steatosis, and insulin resistance. Notably, glucose tolerance was unaffected. Inhibition of Slc25a1 altered hepatic protein acetylation patterns, with decreased cytoplasmic acetylation and increased mitochondrial acetylation. Under HFD conditions, Slc25a1 inhibition promoted fatty acid oxidation and reduced hepatic triglyceride accumulation by deacetylating Cpt1a. Additionally, Slc25a1 inhibition triggered acetylation-induced inactivation of Pdhe1α, leading to a reduction in glucose oxidative catabolism. This was accompanied by enhanced glucose uptake and storage in zebrafish livers. Furthermore, Slc25a1 inhibition under HFD conditions activated the SIRT1/PGC1α pathway, promoting mitochondrial proliferation and enhancing oxidative phosphorylation for energy production. Our findings provide new insights into the role of non-histone protein acetylation via the mitochondrial citrate shuttle in the development of hepatic lipid deposition and hyperglycemia caused by HFD.

Different activation of STAT1 and STAT2 phosphorylation by IFNc, IFNd, and IFNh in tilapia.

Type I IFNs are a subset of cytokines exerting their antiviral effects mainly through the JAK-STAT signalling. Immunogenetic studies have shown that fish possess key components of IFN-JAK-STAT cascade, but the information about the distinct responses of STAT1 and STAT2 to different IFNs is rather limited in fish. Here, we identified and cloned STAT1 and STAT2 genes (named as On-STAT1 and On-STAT2) from tilapia, Oreochromis niloticus. On-STAT1 and On-STAT2 genes were detected in all orangs/tissues examined, and were rapidly induced in spleen, head kidney, and liver following the stimulation of poly(I:C). In addition, the stimulation of poly(I:C), poly(A:T), and different subgroups of recombinant IFNs could induce the expression of On-STAT1 and On-STAT2 in TA-02 cells with distinct induction levels. Importantly, On-STAT2 was rapidly phosphorylated by all three subgroups of IFNs, but the phosphorylation of On-STAT1 was only observed in IFNc- and IFNh-treated TA-02 cells, reflecting the distinct activation of STAT by different subgroups of fish IFNs. The present results thus contribute to better understanding of the JAK-STAT signalling mediated by different subgroups of IFNs in fish.

Inhibiting mitochondrial citrate shuttling induces hepatic triglyceride deposition in Nile tilapia (Oreochromis niloticus) through lipid anabolic remodeling.

The solute carrier family 25 member 1 (Slc25a1)-dependent mitochondrial citrate shuttle is responsible for exporting citrate from the mitochondria to the cytoplasm for supporting lipid biosynthesis and protein acetylation. Previous studies on Slc25a1 concentrated on pathological models. However, the importance of Slc25a1 in maintaining metabolic homeostasis under normal nutritional conditions remains poorly understood. Here, we investigated the mechanism of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis in male Nile tilapia (Oreochromis niloticus). To achieve the objective, we blocked the mitochondrial citrate shuttle by inhibiting Slc25a1 under normal nutritional conditions. Slc25a1 inhibition was established by feeding Nile tilapia with 250 mg/kg 1,2,3-benzenetricarboxylic acid hydrate for 6 weeks or intraperitoneal injecting them with dsRNA to knockdown slc25a1b for 7 days. The Nile tilapia with Slc25a1 inhibition exhibited an obesity-like phenotype accompanied by fat deposition, liver damage and hyperglycemia. Moreover, Slc25a1 inhibition decreased hepatic citrate-derived acetyl-CoA, but increased hepatic triglyceride levels. Furthermore, Slc25a1 inhibition replenished cytoplasmic acetyl-CoA through enhanced acetate pathway, which led to hepatic triglycerides accumulation. However, acetate-derived acetyl-CoA caused by hepatic Slc25a1 inhibition did not activate de novo lipogenesis, but rather modified protein acetylation. In addition, hepatic Slc25a1 inhibition enhanced fatty acids esterification through acetate-derived acetyl-CoA, which increased Lipin1 acetylation and its protein stability. Collectively, our results illustrate that inhibiting mitochondrial citrate shuttle triggers lipid anabolic remodeling and results in lipid accumulation, indicating the importance of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis.

Genome-wide identification, molecular evolution and expression analysis of the B-box gene family in mung bean (Vigna radiata L.).

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.

Case report: A healthy baby achieved after preimplantation genetic testing from an infertile woman with hereditary leiomyomatosis and renal cell cancer syndrome.

Background: Hereditary 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 presentation: We 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. Conclusion: This 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.

Cost-Effectiveness Analysis of 6 Tyrosine Kinase Inhibitors as First-Line Treatment for ALK-Positive NSCLC in China.

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.