Cystatin SN (CST1) Is a Poor Independent Prognostic Biomarker for Gastrointestinal Diffuse Large B-Cell Lymphoma.

BACKGROUND Gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common histological subtype of extra-nodal DLBCL, but the risk factors, prognostic biomarkers, histopathological classifications, and treatment strategies have not had significant progress. Emerging evidence shows that cystatin SN (CST1) is involved in tumor progression in several cancer types, but its role in GI-DLBCL has not been revealed. MATERIAL AND METHODS We established a cohort consisting of 84 patients with GI-DLBCL who underwent surgical resection. The expression of CST1 in the cohort was investigated by immunohistochemistry, which divided the patients into subgroups with low or high expression of CST1. Moreover, the CST1 expression in GI-DLBCL tissues or adjacent GI tissues were compared with RT-qPCR. The correlation between CST1 expression and clinicopathological factors was analyzed with the chi-square test. The prognostic significance of CST1 was estimated by univariate and multivariate analysis, and statistical significance was analyzed with the log-rank test. RESULTS CST1 was aberrantly upregulated in GI-DLBCL tissues compared with in non-tumor GI tissues. High expression of CST1 indicated poor prognosis of GI-DLBCL (P=0.012), and CST1 can be regarded as an independent prognostic biomarker of GI-DLBCL (hazard ratio=3.07). In our study, serum lactate dehydrogenase (P=0.002), performance status (P=0.003), Lugano stage (P=0.002), and International Prognostic Index (P=0.001) were also prognostic factors of GI-DLBCL. CONCLUSIONS CST1 is an independent prognostic biomarker of GI-DLBCL, indicating unfavorable prognosis. Our results suggested that CST1 detection can be a promising method to stratify high-risk patients and guide individual treatment.

Multi-Plexus Nonperfusion Area Segmentation in Widefield OCT Angiography Using a Deep Convolutional Neural Network.

Purpose: To train and validate a convolutional neural network to segment nonperfusion areas (NPAs) in multiple retinal vascular plexuses on widefield optical coherence tomography angiography (OCTA). Methods: This cross-sectional study included 202 participants with a full range of diabetic retinopathy (DR) severities (diabetes mellitus without retinopathy, mild to moderate non-proliferative DR, severe non-proliferative DR, and proliferative DR) and 39 healthy participants. Consecutive 6 × 6-mm OCTA scans at the central macula, optic disc, and temporal region in one eye from 202 participants in a clinical DR study were acquired with a 70-kHz OCT commercial system (RTVue-XR). Widefield OCTA en face images were generated by montaging the scans from these three regions. A projection-resolved OCTA algorithm was applied to remove projection artifacts at the voxel scale. A deep convolutional neural network with a parallel U-Net module was designed to detect NPAs and distinguish signal reduction artifacts from flow deficits in the superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Expert graders manually labeled NPAs and signal reduction artifacts for the ground truth. Sixfold cross-validation was used to evaluate the proposed algorithm on the entire dataset. Results: The proposed algorithm showed high agreement with the manually delineated ground truth for NPA detection in three retinal vascular plexuses on widefield OCTA (mean ± SD F-score: SVC, 0.84 ± 0.05; ICP, 0.87 ± 0.04; DCP, 0.83 ± 0.07). The extrafoveal avascular area in the DCP showed the best sensitivity for differentiating eyes with diabetes but no retinopathy (77%) from healthy controls and for differentiating DR by severity: DR versus no DR, 77%; referable DR (rDR) versus non-referable DR (nrDR), 79%; vision-threatening DR (vtDR) versus non-vision-threatening DR (nvtDR), 60%. The DCP also showed the best area under the receiver operating characteristic curve for distinguishing diabetes from healthy controls (96%), DR versus no DR (95%), and rDR versus nrDR (96%). The three-plexus-combined OCTA achieved the best result in differentiating vtDR and nvtDR (81.0%). Conclusions: A deep learning network can accurately segment NPAs in individual retinal vascular plexuses and improve DR diagnostic accuracy. Translational Relevance: Using a deep learning method to segment nonperfusion areas in widefield OCTA can potentially improve the diagnostic accuracy of diabetic retinopathy by OCT/OCTA systems.

m6A demethylase OsALKBH5 is required for double-strand break formation and repair by affecting mRNA stability in rice meiosis.

N6-methyladenosine (m6A) RNA modification is the most prevalent messenger RNA (mRNA) modification in eukaryotes and plays critical roles in the regulation of gene expression. m6A is a reversible RNA modification that is deposited by methyltransferases (writers) and removed by demethylases (erasers). The function of m6A erasers in plants is highly diversified and their roles in cereal crops, especially in reproductive development essential for crop yield, are largely unknown. Here, we demonstrate that rice OsALKBH5 acts as an m6A demethylase required for the normal progression of male meiosis. OsALKBH5 is a nucleo-cytoplasmic protein, highly enriched in rice anthers during meiosis, that associates with P-bodies and exon junction complexes, suggesting that it is involved in regulating mRNA processing and abundance. Mutations of OsALKBH5 cause reduced double-strand break (DSB) formation, severe defects in DSB repair, and delayed meiotic progression, leading to complete male sterility. Transcriptome analysis and m6A profiling indicate that OsALKBH5-mediated m6A demethylation stabilizes the mRNA level of multiple meiotic genes directly or indirectly, including several genes that regulate DSB formation and repair. Our study reveals the indispensable role of m6A metabolism in post-transcriptional regulation of meiotic progression in rice.

Comparing cranial-caudal-medial and medial-lateral approaches for laparoscopic right hemicolectomy: a propensity score-matched analysis.

BACKGROUND: The cranial-caudal-medial approach (CCMA) has been proposed for laparoscopic right hemicolectomy nowadays. This study aimed to investigate the safety and oncological efficacy of CCMA in the treatment of right-sided colon cancer compared to the medial-lateral approach (MLA). METHODS: Patients diagnosed with right-sided colon cancer were included from February 2015 to June 2018, retrospectively, dividing into the CCMA group and the MLA group. We compared the basic characteristics and the short-term and long-term outcomes in two groups. RESULTS: Two hundred and ninety-six patients were included in this study. The baseline characteristics were similar in two groups. Compared with MLA group, CCMA group exhibited shorter operation time (136.3 ± 25.3 min vs. 151.6 ± 21.5 min, P < 0.001), lower estimated blood loss (44.1 ± 15.2 ml vs. 51.4 ± 26.9 min, P = 0.010), and more harvested lymph nodes (18.5 ± 7.1 vs. 16.5 ± 5.7, P = 0.021). The 5-year overall survival (OS) rate for the CCMA group was 76.5%, and the 5-year disease-free survival (DFS) rate was 72.3%, both of which were not inferior to the MLA group. No significant difference was found between two groups in terms of other clinical parameters. CONCLUSION: The CCMA in laparoscopic right hemicolectomy is safe and feasible, making the anatomical plane clearer. This approach can shorten the operation time, reduce intraoperative blood loss, harvest more lymph nodes, and yield satisfactory oncological outcomes.

Three Ru(II) complexes modulate the antioxidant transcription factor Nrf2 to overcome cisplatin resistance.

Here, we designed, synthesized and characterized three new cyclometalated Ru(II) complexes, [Ru(phen)2(1-(4-Ph-Ph)-IQ)]+ (phen = 1,10-phenanthroline, IQ = isoquinoline, RuIQ9), [Ru(phen)2(1-(4-Ph-Ph)-7-OCH3-IQ)]+ (RuIQ10), and [Ru(phen)2(1-(4-Ph-Ph)-6,7-(OCH3)2-IQ)]+ (RuIQ11). The cytotoxicity experiments conducted on both 2D and 3D multicellular tumor spheroids (MCTSs) indicated that complexes RuIQ9-11 exhibited notably higher cytotoxicity against A549 and A549/DDP cells when compared to the ligands and precursor compounds as well as clinical cisplatin. Moreover, the Ru(II) complexes displayed low toxicity when tested on normal HBE cells in vitro and exposed to zebrafish embryos in vivo. In addition, complexes RuIQ9-11 could inhibit A549 and A549/DDP cell migration and proliferation by causing cell cycle arrest, mitochondrial dysfunction, and elevating ROS levels to induce apoptosis in these cells. Mechanistic studies revealed that RuIQ9-11 could suppress the expression of Nrf2 and its downstream antioxidant protein HO-1 by inhibiting Nrf2 gene transcription in drug-resistant A549/DDP cells. Simultaneously, they inhibited the expression of efflux proteins MRP1 and p-gp in drug-resistant cells, ensuring the accumulation of the complexes within the cells. This led to an increase in intracellular ROS levels in drug-resistant cells, ultimately causing damage and cell death, thus overcoming cisplatin resistance. More importantly, RuIQ11 could effectively inhibit the migration and proliferation of drug-resistant cells within zebrafish, addressing the issue of cisplatin resistance. Accordingly, the prepared Ru(II) complexes possess significant potential for development as highly effective and low-toxicity lung cancer therapeutic agents to overcome cisplatin resistance.

Structural Regulation of NiFe LDH under Spontaneous Corrosion to Enhance the Oxygen Evolution Properties.

Electrochemical water splitting holds promise for sustainable hydrogen production but restricted by the sluggish reaction kinetics at the anodic oxygen evolution. Herein, we present a room-temperature spontaneous corrosion strategy to convert inexpensive iron (Fe) on iron foam substrates into highly active and stable self-supporting nickel iron layered hydroxide (NiFe LDH) catalysts. The corrosion evolution mechanisms are elucidated combining ex-situ scanning electron microscopy (SEM) and X-ray photo electron spectroscopy (XPS) techniques, demonstrating precise control over the concentration of Ni2+ and reaction time to achieve controllable micro-structures of NiFe LDH. Taking advantage of the self-supporting morphology and hierarchical micro-/nano- structure, the NiFe LDH with optimized Ni2+ concentration and reaction time exhibits significant small overpotentials of 160 mV and 200 mV for the OER at current densities of 10 mA cm-2 and 100 mA cm-2 respectively, showcasing excellent OER activities. Furthermore, this catalyst demonstrates superior reaction kinetics, high electrochemical stability, and excellent integral water splitting performance when coupled with a commercial Pt/C cathode. The energy-efficient, cost-effective, and scalable spontaneous corrosion strategy opens new avenues for the development of high-electrochemical-interface catalysts.

Preliminary study on the mechanism of SAHA in the treatment of refractory epilepsy induced by GABRG2(F343L) mutation.

Mutations in the γ-amino butyric acid type A (GABAA) receptor γ2 subunit gene, GABRG2, have been associated with refractory epilepsy. Increasing evidence indicates that suberoylanilide hydroxamic acid (SAHA), a broad-spectrum histone acetyltransferases (HDACs) inhibitor, can inhibit seizure onset. However, the mechanisms involved remains unknown. The present study aimed to explore the anti-epileptic effect and underlying mechanisms of SAHA in the treatment of refractory epilepsy induced by GABRG2 mutation. In the zebrafish line expressing human mutant GABRG2(F343L), Tg(hGABRG2F343L), SAHA was found to reduce seizure onset, swimming activity, and neuronal activity. In both Tg(hGABRG2F343L) zebrafish and HEK293T cells transfected with GABAA receptor subunits, SAHA could improve the pan-acetylation level and reduce the expression of HDAC1/10. The decreased expressions of GABAA receptor subunits could be rescued by SAHA treatment both in vivo and in vitro, which might be the result of increased gene transcription and protein trafficking. The up-regulated acetylation of histone H3 and H4 as well as Bip expression might be involved in the process. Taken together, our data proved that both histone and non-histone acetylation might contribute to the anti-epileptic effect of SAHA in refractory epilepsy caused by GABRG2(F343L) mutation, demonstrating SAHA as a promising therapeutic agent for refractory epilepsy.

Unlocking ultra-high holographic information capacity through nonorthogonal polarization multiplexing.

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

Genome-Wide Association Studies of Growth Trait Heterosis in Crossbred Meat Rabbits.

The application of heterosis can not only effectively improve the disease resistance and meat quality of livestock, but also significantly enhance the reproduction and growth of livestock and poultry. We conducted genome-wide association studies using data from F2 crossbred meat rabbits to screen out candidate genes with significant dominant effects associated with economic trait variation. High-throughput sequencing technology was used to obtain SNPs covering the whole genome to evaluate the homozygosity of the population genome, and analyze the number, length, frequency, and distribution of ROHs in the population. Candidate genes related to economic traits of meat rabbits were searched based on high-frequency ROH regions. After quality control filtering of genotype data, 380 F2 crossbred rabbits were identified with 78,579 SNPs and 42,018 ROHs on the autosomes. The fitting of the Logistic growth curve model showed that 49-day-old rabbits were a growth inflection point. Then, through genome-wide association studies, 10 SNP loci and seven growth trait candidate genes were found to be significantly related to body weight in meat rabbits at 84 days of age. In addition, we revealed the functional roles and locations of 20 candidate genes in the high-frequency ROH region associated with economic traits in meat rabbits. This study identified potential genes associated with growth and development in the high-frequency ROH region of meat rabbits. In this study, the identified candidate genes can be used as molecular markers for assisted selection in meat rabbits. At the same time, the inbreeding situation based on ROH assessment can provide reference for breeding and breeding preservation of meat rabbits.

Growth, Antioxidant Capacity, and Liver Health in Largemouth Bass (Micropterus salmoides) Fed Multi-Strain Yeast-Based Paraprobiotic: A Lab-to-Pilot Scale Evaluation.

A multi-strain yeast-based paraprobiotic (MsYbP) comprising inactive cells and polysaccharides (ß-glucan, mannan oligosaccharides, and oligosaccharides) derived from Saccharomyces cerevisiae and Cyberlindnera jadinii could ensure optimal growth and health in farmed fish. This study assessed the impact of an MsYbP on the growth, immune responses, antioxidant capacities, and liver health of largemouth bass (Micropterus salmoides) through lab-scale (65 days) and pilot-scale (15 weeks) experiments. Two groups of fish were monitored: one fed a control diet without the MsYbP and another fed 0.08% and 0.1% MsYbP in the lab-scale and pilot-scale studies, respectively (referred to as YANG). In the lab-scale study, four replicates were conducted, with 20 fish per replicate (average initial body weight = 31.0 ± 0.8 g), while the pilot-scale study involved three replicates with approximately 1500 fish per replicate (average initial body weight = 80.0 ± 2.2 g). The results indicate that the MsYbP-fed fish exhibited a significant increase in growth in both studies (p < 0.05). Additionally, the dietary MsYbP led to a noteworthy reduction in the liver function parameters (p < 0.05), such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AKP), and hepatic nuclear density, indicating improved liver health. Furthermore, the dietary MsYbP elevated the antioxidative capacity of the fish by reducing their malondialdehyde levels and increasing their levels and gene expressions related to antioxidative markers, such as total antioxidant ca-pacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), catalase (CAT), nuclear factor erythroid 2-related factor 2 (nrf2) and kelch-1ike ech-associated protein (keap1) in both studies (p < 0.05). In terms of hepatic immune responses, the lab-scale study showed an increase in inflammation-related gene expressions, such as interleukin-1ß (il-1ß) and transforming growth factor ß1 (tgf-ß1), while the pilot-scale study significantly suppressed the expressions of genes related to inflammatory responses, such as tumor necrosis factor α (tnfα) and interleukin-10 (il-10) (p < 0.05). In summary, our findings underscore the role of dietary multi-strain yeast-based paraprobiotics in enhancing the growth and liver health of largemouth bass, potentially through increased antioxidative capacity and the modulation of immune responses, emphasizing the significance of employing yeast-based paraprobiotics in commercial conditions.

Intraperitoneal administration of doxorubicin-encapsulated Brucea javanica oil nanoemulsion against malignant ascites.

Malignant ascites is a common complication of advanced cancers, which reduces survival rates and diminishes patients' quality of life. Intraperitoneal chemotherapy is a conventional method for treating cancer-related ascites, but the poor drug retention of conventional drugs requires frequent administration to maintain sustained anti-tumor effects. In this study, we encapsulated doxorubicin (DOX) into Brucea javanica oil (BJO) to develop a water-in-oil (W/O) nanoemulsion called BJO@DOX for the treatment of malignant ascites through in-situ intraperitoneal administration. BJO significantly induced apoptosis of S180 cells by upregulating the expression of p53 and caspase-3 (cleaved). Additionally, BJO notably downregulated the expression of Bcl-2, further promoting apoptosis of S180 cells. Cell apoptosis significantly inhibited ascites formation and tumor cell proliferation in a mouse model. The combination of DOX and BJO exhibited satisfactory synergistic effects, consequently prolonging the survival period of mice. Histological examination of major organs indicated that the nanoemulsion had excellent biosafety in vivo. The BJO@DOX nanoemulsion represents a promising platform for in-situ chemotherapy of malignant ascites.

Insights into the terahertz response of L-glutamic acid and its receptor.

L-Glutamic acid (L-Glu) is a basic unit of proteins and also serves as an important neurotransmitter in the central nervous system. Its structural properties are critical for biological functions and selective receptor recognition. Although this molecule has been extensively studied, the low frequency vibrational behavior that is closely related to conformational changes and the intermolecular interactions between L-Glu and its receptors are still unclear. In this study, we acquired the fingerprint spectrum of L-Glu by using air plasma terahertz (THz) time-domain spectroscopy in the 0.5-18 THz range. The low frequency vibrational characteristics of L-Glu were investigated through density functional theory (DFT) calculations. The THz responses of the ligand binding domain of the NMDAR-L-Glu complex were studied by the ONIOM method, with a focus on discussing the normal modes and interactions of ligand L-Glu and water molecules. The results illustrate that THz spectroscopy exhibits a sensitive response to the influence of L-Glu on the structure of the NMDAR. The water molecules in proteins have various strong vibration modes in the THz band, showing specificity, diversity and complexity of vibrational behavior. There is potential for influencing and regulating the structural stability of the NMDAR-L-Glu complex through water molecules.

Intraoperative goal-directed fluid management and postoperative brain edema in patients having high-grade gliomas resections: a randomized trial.

INTRODUCTION: Patients with high-grade gliomas often have severe brain edema. Goal-directed fluid management protects neurological function, but whether reduces postoperative brain edema remains unknown. METHODS: Patients having elective resection of supratentorial malignant gliomas were randomly assigned to goal-directed versus routine fluid management. Patients assigned to goal-directed management group were given 3 mL kg-1 hydroxyethyl starch solution when stroke volume variation exceeded 15% for 5 minutes. Fluid was managed per routine by attending anesthesiologists in reference patients. The primary outcome was cerebral edema volume after surgery as assessed by computerized tomography. RESULTS: A total of 480 eligible patients were randomly assigned to the goal-directed (n = 240) or the routine fluid management group (n = 240). The amounts of crystalloid (5.4 vs. 7.0 ml kg-1 hour-1, P < 0.001), colloid (1.1 vs. 1.7 ml kg-1 hour-1, P < 0.001), and overall fluid balance (0.3 vs. 1.9 ml kg-1 hour-1, P < 0.001) were significantly lower in goal-directed fluid management. There was no significant difference in postoperative brain edema volume between groups (36.0 cm3 vs. 38.9 cm3, mean difference: 0.18cm3, 95% CI: -5.7 to 5.9). Goal-directed patients had lower intraoperative dural tension (risk ratio: 0.63, 95% CI: 0.50 to 0.80, P < 0.001). There was no significant difference in Karnofsky Performance Status between the two groups at 30 days after surgery. CONCLUSIONS: Goal-directed fluid therapy substantially reduced intravenous fluid volumes, but did not reduce postoperative brain edema in patients having brain tumor resections.

A comprehensive exploration of hydrogel applications in multi-stage skin wound healing.

Hydrogels, as an emerging biomaterial, have found extensive use in the healing of wounds due to their distinctive physicochemical structure and functional properties. Moreover, hydrogels can be made to match a range of therapeutic requirements for materials used in wound healing through specific functional modifications. This review provides a step-by-step explanation of the processes involved in cutaneous wound healing, including hemostasis, inflammation, proliferation, and reconstitution, along with an investigation of the factors that impact these processes. Furthermore, a thorough analysis is conducted on the various stages of the wound healing process at which functional hydrogels are implemented, including hemostasis, anti-infection measures, encouraging regeneration, scar reduction, and wound monitoring. Next, the latest progress of multifunctional hydrogels for wound healing and the methods to achieve these functions are discussed in depth and categorized for elucidation. Finally, perspectives and challenges associated with the clinical applications of multifunctional hydrogels are discussed.

Lycopene alleviates Deoxynivalenol-induced toxicity in Porcine intestinal epithelial cells by mediating mitochondrial function.

Deoxynivalenol (DON) is widely found in food and feed, posing a threat to human and animal health. Lycopene (Lyc) is a natural plant extracts with significant antioxidant properties. This study was conducted to investigate the protective effects of Lyc on IPEC-J2 cells upon DON exposure. The detection of cell viability and trypan blue staining showed that Lyc alleviated cell damage and decreased cell apoptotic rate induced by DON. The analysis of reactive oxygen species (ROS) level and antioxidant parameter measurements showed that Lyc significantly down-regulated the content of ROS and restored antioxidant enzyme activity. Furthermore, mitochondrial membrane potential (ΔΨm) detection, mitochondrial DNA copy number (mtDNAcn) assay and adenosine triphosphate (ATP) concentration detection showed Lyc improved mitochondrial function after DON exposure. The results of transcriptome analysis, ROS detection and CCK8 assay suggested that Lyc may activated the oxidative phosphorylation (OXPHOS) to improve mitochondrial function. Conclusively, our results suggested that Lyc alleviated DON-induced oxidative stress by improving mitochondrial function through OXPHOS signaling pathway.

The double mediating effect of stress regulation and life satisfaction on music use as a coping mechanism and happiness in Chinese older adults during the COVID-19 pandemic.

BACKGROUND: This study investigated the relationship between music use as a coping mechanism and subjective happiness among Chinese older adults (COAs) during Coronavirus disease 2019 (COVID-19); it also focused on the mediating effect of stress regulation by music and life satisfaction in this relationship. METHODS: Participants were 329 male and female Chinese adults aged 60 years or older. Data were collected using the Sojump application for an online survey. The double mediating effect was analyzed using PROCESS Macro 3.5 Model 6. RESULTS: The results revealed that music use as a coping mechanism and stress regulation by music were not significantly correlated with subjective happiness of COAs, whereas these were positively correlated with their life satisfaction. Additionally, life satisfaction of COAs was positively correlated with subjective happiness. Stress regulation by music and life satisfaction completely mediated the relationship between music use as a coping mechanism and subjective happiness of COAs during COVID-19. In the double mediation model, music use as a coping mechanism positively influenced stress regulation by music (ß = 0.704), stress regulation by music positively influenced life satisfaction (ß = 0.162), and life satisfaction positively influenced subjective happiness (ß = 0.498). CONCLUSION: Therefore, music can promote happiness in COAs in stressful situations through stress regulation and life satisfaction.

Phagocytic Plasma Cells in Teleost Fish Provide Insights into the Origin and Evolution of B Cells in Vertebrates.

Teleost IgM+ B cells can phagocytose, like mammalian B1 cells, and secrete Ag-specific IgM, like mammalian B2 cells. Therefore, teleost IgM+ B cells may have the functions of both mammalian B1 and B2 cells. To support this view, we initially found that grass carp (Ctenopharyngodon idella) IgM+ plasma cells (PCs) exhibit robust phagocytic ability, akin to IgM+ naive B cells. Subsequently, we sorted grass carp IgM+ PCs into two subpopulations: nonphagocytic (Pha-IgM+ PCs) and phagocytic IgM+ PCs (Pha+IgM+ PCs), both of which demonstrated the capacity to secrete natural IgM with LPS and peptidoglycan binding capacity. Remarkably, following immunization of grass carp with an Ag, we observed that both Pha-IgM+ PCs and Pha+IgM+ PCs could secrete Ag-specific IgM. Furthermore, in vitro concatenated phagocytosis experiments in which Pha-IgM+ PCs from an initial phagocytosis experiment were sorted and exposed again to beads confirmed that these cells also have phagocytic capabilities, thereby suggesting that all teleost IgM+ B cells have phagocytic potential. Additionally, we found that grass carp IgM+ PCs display classical phenotypic features of macrophages, providing support for the hypothesis that vertebrate B cells evolved from ancient phagocytes. These findings together reveal that teleost B cells are a primitive B cell type with functions reminiscent of both mammalian B1 and B2 cells, providing insights into the origin and evolution of B cells in vertebrates.

Multi-omics analysis reveals the impact of gut microbiota on antipsychotic-induced weight gain in schizophrenia.

Emerging evidence indicates that gut microbial dysbiosis is associated with the development of antipsychotic-induced weight gain in schizophrenia (SZ). However, the exact taxonomic composition and functionality that constitute the "obesogenic" microbial profile remain elusive. Our retrospective survey identified two groups of the SZ population separated by BMI, with 1/3 of patients developing overweight/obesity after chronic antipsychotic treatment. Based on multi-omics analysis, we observed altered gut microbiota in SZ patients with overweight/obesity, characterized by a reduction in several beneficial bacteria genera, including Bacteroides, Parabacteroides, Akkermansia, and Clostridium. This microbial dysbiosis was accompanied by disrupted energy expenditure and nutritional metabolism, worsened metabolic indices, and reduced levels of beneficial metabolites, e.g. indole-3-carboxylic acid and propionic acid. Moreover, leveraging data from first-episode drug-naïve schizophrenia (FSZ) patients at one-month and one-year follow-up, both artificial neural network and random forest classifier-based prediction models demonstrated a strong ability of microbial profiles to predict antipsychotic-induced weight gain. Importantly, FSZ patients with higher relative abundance of Parabacteria distasonis were less susceptible to antipsychotic-induced weight gain. Thus, gut microbiota could serve as a noninvasive approach to predict antipsychotic-induced weight gain, guiding clinical antipsychotics administration and developing novel therapeutic strategies for weight management in SZ.