Exact burst-size distributions for gene-expression models with complex promoter structure.

In prokaryotic and eukaryotic cells, most genes are transcribed in a bursty fashion on one hand and complex gene regulations may lead to complex promoter structure on the other hand. This raises an unsolved issue: how does promoter structure shape transcriptional bursting kinetics characterized by burst size and frequency? Here we analyze stochastic models of gene transcription, which consider complex regulatory mechanisms. Notably, we develop an efficient method to derive exact burst-size distributions. The analytical results show that if the promoter of a gene contains only one active state, the burst size indeed follows a geometric distribution, in agreement with the previous result derived under certain limiting conditions. However, if it contains a multitude of active states, the burst size in general obeys a non-geometric distribution, which is a linearly weighted sum of geometric distributions. This superposition principle reveals the essential feature of bursting kinetics in complex cases of transcriptional regulation although it seems that there has been no direct experimental confirmation. The derived burst-size distributions not only highlight the importance of promoter structure in regulating bursting kinetics, but can be also used in the exact inference of this kinetics based on experimental data.

Design, Synthesis, and Biological Evaluation of Lysine-Stapled Peptide Inhibitors of p53-MDM2/MDMX Interactions with Potent Antitumor Activity In Vivo.

We introduce novel lysine-stapled peptide inhibitors targeting p53-MDM2/MDMX interactions. Leveraging the model peptides pDI (LTFEHYWAQLTS) and PMI-M3 (LTFLEYWAQLMQ) as starting points, a series of lysine-stapled analogues were designed and synthesized. Through in vitro cell assay screening, two lead compounds, SPDI-48-T1 and SPMI-48-T3, were identified for their excellent antiproliferation activity. Fluorescence polarization assays revealed that both compounds exhibited strong binding affinities against MDM2 and MDMX, ascertained by Kd values within the low micromolar spectrum. Further characterization of SPDI-48-T1 and SPMI-48-T3 demonstrated that SPDI-48-T1 possessed superior cell permeability and serum stability. Notably, SPDI-48-T1 displayed a dose-dependent suppression of tumor growth in an HCT116 xenograft mouse model. Our findings indicate that SPDI-48-T1 holds promise as a lead compound for further development as an anticancer agent by modulating p53-MDM2/MDMX interactions. Additionally, this study also proved that the lysine stapling strategy may serve as a robust approach for generating peptide ligands targeting other protein-protein interactions.

RBM39 enhances cholangiocarcinoma growth through EZH2-mediated WNT7B/ß-catenin pathway.

BACKGROUND AND AIMS: The RNA-binding motif protein 39 (RBM39) functions as both an RNA-binding protein and a splicing factor in a variety of cancer types. However, the function of RBM39 in cholangiocarcinoma (CCA) remains undefined. In this study, we aimed to investigate the role of RBM39 in CCA and explore its potential as a therapeutic target. METHODS: The expression of RBM39 in CCA was investigated by analyzing human CCA tumor specimens. CRISPR/Cas9 or shRNA-mediated depletion of RBM39 was performed in vitro and in vivo to document the oncogenic role of RBM39 in CCA. The anti-tumor effect of the RBM39 inhibitor Indisulam in combination with the EZH2 degrader MS177 was assessed in vitro and in vivo. RESULTS: RBM39 is significantly increased in human CCA tissues and associated with a poor prognosis in CCA patients. Depletion of RBM39 by CRISPR/Cas9 or shRNA inhibited CCA cell proliferation in vitro and prevented CCA development and tumor growth in mice. Mechanistically, our results showed that depletion of RBM39 suppressed EZH2 expression via disrupting its mRNA splicing. RBM39-regulated EZH2 controls WNT7B/ß-catenin activity. Pharmacological co-targeting of RBM39 (with Indisulam) and EZH2 (with MS177) resulted in a synergistic antitumor effect, both in vitro and in vivo. CONCLUSION: This study discloses a novel RBM39-EZH2-ß-catenin signaling axis that is crucial for CCA growth. Our findings suggest that simultaneous inhibition of RBM39 and EZH2 presents a promising therapeutic strategy for CCA treatment.

Contamination of the traditional medicine Radix Dipsaci with aflatoxin B1 impairs hippocampal neurogenesis and cognitive function in a mouse model of osteoporosis.

BACKGROUND: Aflatoxin B1, which can penetrate the blood-brain barrier and kill neural cells, can contaminate traditional herbal medicines, posing a significant risk to human health. The present study examined cellular, cognitive and behavioral consequences of aflatoxin B1 contamination of the anti-osteoporotic medicine Radix Dipsaci. METHODS: A mouse model of osteoporosis was created by treating the animals with all-trans-retinoic acid. Then the animals were treated intragastically with water decoctions of Radix Dipsaci that contained detectable aflatoxin B1 or not. The animals were compared in terms of mineral density and mineral salt content of bone, production of pro-inflammatory factors, neurogenesis and microglial activation in hippocampus, as well as behavior and cognitive function. RESULTS: Contamination of Radix Dipsaci with aflatoxin B1 significantly reduced the medicine's content of bioactive saponins. It destroyed the ability of the herbal decoction to improve mineral density and mineral salt content in the bones of diseased mice, and it induced the production of the oxidative stress marker malondialdehyde as well as the pro-inflammatory cytokines interleukin-1ß and tumor necrosis factor-α. Aflatoxin B1 contamination inhibited formation of new neurons and increased the proportion of activated microglia in the hippocampus. These neurological changes were associated with anhedonia, behavioral despair, and deficits in short-term memory and social memory. CONCLUSION: Contamination of Radix Dipsaci with aflatoxin B1 not only eliminates the herbal decoction's anti-osteoporotic effects, but it also induces neurotoxicity that can lead to cognitive decline and behavioral abnormalities. Such contamination should be avoided through tightly regulated production and quality control of medicinal herbs.

Near 100% Conversion of Acetylene to High-purity Ethylene at Ampere-Level Current.

Direct production of high-purity ethylene from acetylene using renewable energy through electrocatalytic semi-hydrogenation presents a promising alternative to traditional thermocatalytic processes. However, the low conversion of acetylene results in a significant amount of acetylene impurities in the product, necessitating additional purification steps. Herein, a tandem electrocatalytic system that integrates acetylene electrolyzer and zinc-acetylene battery units for high-purity ethylene production is designed. The ultrathin CuO nanoribbons with enriched oxygen vacancies (CuO1-x NRs) as electrocatalysts achieve a remarkable 93.2% Faradaic efficiency of ethylene at an ampere-level current density of 1.0 A cm-2 in an acetylene electrolyzer, and the power density reaches 3.8 mW cm-2 in a zinc-acetylene battery under acetylene stream. Moreover, the tandem electrocatalysis system delivers a single-pass acetylene conversion of 99.998% and ethylene selectivity of 96.1% at a high current of 1.4 A. Experimental data and calculations demonstrate that the presence of oxygen vacancies accelerates water dissociation to produce active hydrogen atoms while preventing the over-hydrogenation of ethylene. Furthermore, techno-economic analysis reveals that the tandem system can dramatically reduce the overall ethylene production cost compared to the conventional thermocatalytic processes. A novel strategy for complete acetylene-to-ethylene conversion under mild conditions, establishing a non-petroleum route for the production of ethylene is reported.

YAP activation in liver macrophages via depletion of MST1/MST2 enhances liver inflammation and fibrosis in MASLD.

Macrophages have been recognized as pivotal players in the progression of MASLD/MASH. However, the molecular mechanisms underlying their multifaceted functions in the disease remain to be further clarified. In the current study, we developed a new mouse model with YAP activation in macrophages to delineate the effect and mechanism of YAP signaling in the pathogenesis of MASLD/MASH. Genetically modified mice, featuring specific depletion of both Mst1 and Mst2 in macrophages/monocytes, were generated and exposed to a high-fat diet for 12 weeks to induce MASLD. Following this period, livers were collected for histopathological examination, and liver non-parenchymal cells were isolated and subjected to various analyses, including single-cell RNA-sequencing, immunofluorescence and immunoblotting and qRT-PCR to investigate the impact of YAP signaling on the progression of MASLD. Our data revealed that Mst1/2 depletion in liver macrophages enhanced liver inflammation and fibrosis in MASLD. Using single-cell RNA-sequencing, we showed that YAP activation via Mst1/2 depletion upregulated the expressions of both pro-inflammatory genes and genes associated with resolution/tissue repair. We observed that YAP activation increases Kupffer cell populations (i.e., Kupffer-2 and Kupffer-3) which are importantly implicated in the pathogenesis of MASLD/MASH. Our data indicate that YAP activation via Mst1/2 deletion enhances both the pro-inflammatory and tissue repairing functions of Kupffer-1 and -2 cells at least in part through C1q. These YAP-regulatory mechanisms control the plasticity of liver macrophages in the context of MASLD/MASH. Our findings provide important evidence supporting the critical regulatory role of YAP signaling in liver macrophage plasticity and the progression of MASLD. Therefore, targeting the Hippo-YAP pathway may present a promising therapeutic strategy for the treatment of MASH.

Coupling photocatalytic CO2 reduction and CH3OH oxidation for selective dimethoxymethane production.

Currently, conventional dimethoxymethane synthesis methods are environmentally unfriendly. Here, we report a photo-redox catalysis system to generate dimethoxymethane using a silver and tungsten co-modified blue titanium dioxide catalyst (Ag.W-BTO) by coupling CO2 reduction and CH3OH oxidation under mild conditions. The Ag.W-BTO structure and its electron and hole transfer are comprehensively investigated by combining advanced characterizations and theoretical studies. Strikingly, Ag.W-BTO achieve a record photocatalytic activity of 5702.49 µmol g-1 with 92.08% dimethoxymethane selectivity in 9 h of ultraviolet-visible irradiation without sacrificial agents. Systematic isotope labeling experiments, in-situ diffuse reflectance infrared Fourier-transform analysis, and theoretical calculations reveal that the Ag and W species respectively catalyze CO2 conversion to *CH2O and CH3OH oxidation to *CH3O. Subsequently, an asymmetric carbon-oxygen coupling process between these two crucial intermediates produces dimethoxymethane. This work presents a CO2 photocatalytic reduction system for multi-carbon production to meet the objectives of sustainable economic development and carbon neutrality.

Recommendations for broadening eligibility criteria in esophagus cancer clinical trials: the mortality disparity of esophagus cancer as a first or second primary malignancy.

Background: Esophagus cancer as a second primary malignancy (esophagus-2) is increasingly common, but its prognosis is poorly understood. This study aims to examine the overall, non-cancer related and cancer-specific survival of patients diagnosed with esophagus-2 compared to the first primary esophagus cancer (esophagus-1). Methods: We included primary esophagus cancer patients diagnosed from 1975 to 2019 in the Surveillance, Epidemiology, and End Results program. Esophagus-2 was identified in patients with a previous diagnosis of non-esophageal primary malignancy. Hazard ratios of overall, esophagus cancer-specific and non-cancer related mortality were estimated among patients with esophagus-2 compared to esophagus-1, adjusting for age, gender, tumor stage and other demographic and clinical characteristics. Results: A total of 74,521 and 14,820 patients were identified as esophagus-1 and esophagus-2 respectively. Esophagus-2 patients suffered lower risk of esophagus cancer-specific mortality in initial 5 years but with similar risk thereafter, independent of tumor characteristics and treatment. In the first 5 years after diagnosis, patients with esophagus-2 had similar risk of overall mortality with those with esophagus-1 but increased risk thereafter. As for non-cancer related mortality, esophagus-2 patients had higher risk all along. Conclusions: Esophagus-2 patients should not be entirely excluded from clinical trial and a 3-year exclusion window is suggested. A conservative approach to manage esophagus-2 solely based on malignancy history is not supported but effort should be put into surveillance, prevention and management of the comorbidities and complications for the first malignancy.

The sweating process promotes toxigenic fungi expansion and increases the risk of combined contamination of mycotoxins in Radix Dipsaci.

Sweating is one of the most important processing methods of Chinese medicinal herbs. However, the high temperature and humidity environment required for sweating Chinese medicinal herbs makes it very easy for fungi to breed, especially toxigenic fungi. The mycotoxins produced by these fungi will then contaminate the Chinese medicinal herbs. In this study, we explored the changes in mycobiota, toxigenic fungi, and mycotoxins with and without sweating in Radix Dipsaci (RD), a typical representative of traditional Chinese medicine that requires processing through sweating. We also isolated and identified the toxigenic fungi from RD, whether they were subjected to sweating treatment or not, and examined their toxigenic genes and ability. The results showed that the detection rate of mycotoxins (aflatoxins, ochratoxins, zearalenone, and T-2 toxin) in RD with sweating was 36%, which was 2.25-fold higher than that in RD without sweating. We also detected T-2 toxin in the RD with sweating, whereas it was not found in the RD without sweating. The sweating process altered the fungal composition and increased the abundance of Fusarium and Aspergillus in RD. Aspergillus and Fusarium were the most frequently contaminating fungi in the RD. Morphological and molecular identification confirmed the presence of key toxigenic fungal strains in RD samples, including A. flavus, A. westerdijkiae, F. oxysporum and F. graminearum. These four fungi, respectively, carried AflR, PKS, Tri7, and PKS14, which were key genes for the biosynthesis of aflatoxins, ochratoxins, zearalenone, and T-2 toxin. The toxigenic ability of these four fungal strains was verified in different matrices. We also found that A. flavus, A. westerdijkiae, and F. oxysporum were isolated in RD both with sweating and without sweating, but their isolation frequency was significantly higher in the RD with sweating than in the RD without sweating. F. graminearum was not isolated from RD without sweating, but it was isolated from RD with sweating. These findings suggest that the sweating process promotes the expansion of toxigenic fungi and increases the risk of combined mycotoxin contamination in RD.

Priming of hippocampal microglia by IFN-γ/STAT1 pathway impairs social memory in mice.

Social behavior is inextricably linked to the immune system. Although IFN-γ is known to be involved in social behavior, yet whether and how it encodes social memory remains unclear. In the current study, we injected with IFN-γ into the lateral ventricle of male C57BL/6J mice, and three-chamber social test was used to examine the effects of IFN-γ on their social preference and social memory. The morphology of microglia in the hippocampus, prelimbic cortex and amygdala was examined using immunohistochemistry, and the phenotype of microglia were examined using immunohistochemistry and enzyme-linked immunosorbent assays. The IFN-γ-injected mice were treated with lipopolysaccharide, and effects of IFN-γ on behavior and microglial responses were evaluated. STAT1 pathway and microglia-neuron interactions were examined in vivo or in vitro using western blotting and immunohistochemistry. Finally, we use STAT1 inhibitor or minocycline to evaluated the role of STAT1 in mediating the microglial priming and effects of primed microglia in IFN-γ-induced social dysfunction. We demonstrated that 500 ng of IFN-γ injection results in significant decrease in social index and social novelty recognition index, and induces microglial priming in hippocampus, characterized by enlarged cell bodies, shortened branches, increased expression of CD68, CD86, CD74, CD11b, CD11c, CD47, IL-33, IL-1ß, IL-6 and iNOS, and decreased expression of MCR1, Arg-1, IGF-1 and BDNF. This microglia subpopulation is more sensitive to LPS challenge, which characterized by more significant morphological changes and inflammatory responses, as well as induced increased sickness behaviors in mice. IFN-γ upregulated pSTAT1 and STAT1 and promoted the nuclear translocation of STAT1 in the hippocampal microglia and in the primary microglia. Giving minocycline or STAT1 inhibitor fludarabin blocked the priming of hippocampal microglia induced by IFN-γ, ameliorated the dysfunction in hippocampal microglia-neuron interactions and synapse pruning by microglia, thereby improving social memory deficits in IFN-γ injected mice. IFN-γ initiates STAT1 pathway to induce priming of hippocampal microglia, thereby disrupts hippocampal microglia-neuron interactions and neural circuit link to social memory. Blocking STAT1 pathway or inhibiting microglial priming may be strategies to reduce the effects of IFN-γ on social behavior.

Ordered mesoporous carbon with binary CoFe atomic species for highly efficient oxygen reduction electrocatalysis.

The exploration of powerful, efficient and precious metal-free electrocatalysts for facilitating the sluggish kinetics of the oxygen reduction reaction (ORR) is a crucial endeavor in the development and application of energy conversion and storage devices. Herein, we have rationally designed and synthesized bimetallic CoFe species consisting of CoFe nanoparticles and atomically dispersed dual atoms anchored on an ordered mesoporous carbon matrix (CoFe/NC) as highly efficient ORR electrocatalysts. The pyrolyzation temperature for CoFe/NC plays a vital role in regulating the morphology and composition of both the carbon matrix and CoFe species. The optimized CoFe/NC-750 exhibits a favorable ORR performance in 0.1 M KOH with a high half-wave potential (E1/2) of 0.87 V vs. RHE, excellent tolerance to methanol and remarkable durability (no obvious decrease in E1/2 value after 3000 cycles), all of which are superior to the performance of commercial Pt/C. Experimental measurements and density functional theory (DFT) calculations reveal that the improved ORR performance of CoFe/NC-750 is mainly attributed to the electronic structure of atomically dispersed Fe active sites modulated by the surrounding CoFe alloys and Co single atoms, which accelerates the dissociation and reduction of intermediate OH* species and promotes the ORR process.

The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant cancer of the biliary tract with poor prognosis. Further mechanistic insights into the molecular mechanisms of CCA are needed to develop more effective target therapy. METHODS: The expression of the histone lysine acetyltransferase KAT2B in human CCA was analyzed in human CCA tissues. CCA xenograft was developed by inoculation of human CCA cells with or without KAT2B overexpression into SCID mice. Western blotting, ChIP-qPCR, qRT-PCR, protein immunoprecipitation, GST pull-down and RNA-seq were performed to delineate KAT2B mechanisms of action in CCA. RESULTS: We identified KAT2B as a frequently downregulated histone acetyltransferase in human CCA. Downregulation of KAT2B was significantly associated with CCA disease progression and poor prognosis of CCA patients. The reduction of KAT2B expression in human CCA was attributed to gene copy number loss. In experimental systems, we demonstrated that overexpression of KAT2B suppressed CCA cell proliferation and colony formation in vitro and inhibits CCA growth in mice. Mechanistically, forced overexpression of KAT2B enhanced the expression of the tumor suppressor gene NF2, which is independent of its histone acetyltransferase activity. We showed that KAT2B was recruited to the promoter region of the NF2 gene via interaction with the transcription factor SP1, which led to enhanced transcription of the NF2 gene. KAT2B-induced NF2 resulted in subsequent inhibition of YAP activity, as reflected by reduced nuclear accumulation of oncogenic YAP and inhibition of YAP downstream genes. Depletion of NF2 was able to reverse KAT2B-induced reduction of nuclear YAP and subvert KAT2B-induced inhibition of CCA cell growth. CONCLUSIONS: This study provides the first evidence for an important tumor inhibitory effect of KAT2B in CCA through regulation of NF2-YAP signaling and suggests that this signaling cascade may be therapeutically targeted for CCA treatment.

Ligand-modified nanoparticle surfaces influence CO electroreduction selectivity.

Improving the kinetics and selectivity of CO2/CO electroreduction to valuable multi-carbon products is a challenge for science and is a requirement for practical relevance. Here we develop a thiol-modified surface ligand strategy that promotes electrochemical CO-to-acetate. We explore a picture wherein nucleophilic interaction between the lone pairs of sulfur and the empty orbitals of reaction intermediates contributes to making the acetate pathway more energetically accessible. Density functional theory calculations and Raman spectroscopy suggest a mechanism where the nucleophilic interaction increases the sp2 hybridization of CO(ad), facilitating the rate-determining step, CO* to (CHO)*. We find that the ligands stabilize the (HOOC-CH2)* intermediate, a key intermediate in the acetate pathway. In-situ Raman spectroscopy shows shifts in C-O, Cu-C, and C-S vibrational frequencies that agree with a picture of surface ligand-intermediate interactions. A Faradaic efficiency of 70% is obtained on optimized thiol-capped Cu catalysts, with onset potentials 100 mV lower than in the case of reference Cu catalysts.

DhuFAP: a platform for gene functional analysis in Dendrobium huoshanense.

BACKGROUND: Dendrobium huoshanense, a traditional medicinal and food plant, has a rich history of use. Recently, its genome was decoded, offering valuable insights into gene function. However, there is no comprehensive gene functional analysis platform for D. huoshanense. RESULT: To address this, we created a platform for gene function analysis and comparison in D. huoshanense (DhuFAP). Using 69 RNA-seq samples, we constructed a gene co-expression network and annotated D. huoshanense genes by aligning sequences with public protein databases. Our platform contained tools like Blast, gene set enrichment analysis, heatmap analysis, sequence extraction, and JBrowse. Analysis revealed co-expression of transcription factors (C2H2, GRAS, NAC) with genes encoding key enzymes in alkaloid biosynthesis. We also showcased the reliability and applicability of our platform using Chalcone synthases (CHS). CONCLUSION: DhuFAP ( www.gzybioinformatics.cn/DhuFAP ) and its suite of tools represent an accessible and invaluable resource for researchers, enabling the exploration of functional information pertaining to D. huoshanense genes. This platform stands poised to facilitate significant biological discoveries in this domain.

A Palladium Catalyst Supported on Boron-Doped Porous Carbon for Efficient Dehydrogenation of Formic Acid.

Formic acid has emerged as a highly promising hydrogen storage material, and the development of efficient catalysts to facilitate its dehydrogenation remains imperative. In this study, a novel catalyst consisting of palladium nanoparticles supported on boron-doped porous carbon (Pd/BPC) was successfully synthesized to enable efficient hydrogen production through the dehydrogenation of formic acid. The impacts of the boron doping ratio, doping temperature, and palladium reduction temperature on the catalyst's performance were systemically investigated. The results demonstrated the Pd/BPC catalyst synthesized with a carbon-to-boron ratio of 1:5 by calcination at 900 °C and subsequent reduction at 60 °C exhibited superior formic acid dehydrogenation performance, being 2.9 and 3.8 times greater than that of the Pd/PC catalysts without boron doping and commercial Pd/C, respectively. Additionally, the catalyst showed excellent cycle stability with no significant activity reduction after five consecutive cycles. Experimental and theoretical results reveal that boron doping not only facilitates the homogenous distribution of Pd nanoparticles but also induces a stronger support-metal interaction, thereby reinforcing the catalytic performance. This research is expected to provide valuable insights into the economically viable and efficient production of environmentally friendly hydrogen energy.

Exact results for gene-expression models with general waiting-time distributions.

Complex molecular details of transcriptional regulation can be coarse-grained by assuming that reaction waiting times for promoter-state transitions, the mRNA synthesis, and the mRNA degradation follow general distributions. However, how such a generalized two-state model is analytically solved is a long-standing issue. Here we first present analytical formulas of burst-size distributions for this model. Then, we derive an iterative equation for the mRNA moment-generating function, by which mRNA raw and binomial moments of any order can be conveniently calculated. The analytical results obtained in the special cases of phase-type waiting-time distributions not only provide insights into the mechanisms of complex transcriptional regulations but also bring conveniences for experimental data-based statistical inferences.

Selective Electrified Propylene-to-Propylene Glycol Oxidation on Activated Rh-Doped Pd.

Renewable-energy-powered electrosynthesis has the potential to contribute to decarbonizing the production of propylene glycol, a chemical that is used currently in the manufacture of polyesters and antifreeze and has a high carbon intensity. Unfortunately, to date, the electrooxidation of propylene under ambient conditions has suffered from a wide product distribution, leading to a low faradic efficiency toward the desired propylene glycol. We undertook mechanistic investigations and found that the reconstruction of Pd to PdO occurs, followed by hydroxide formation under anodic bias. The formation of this metastable hydroxide layer arrests the progressive dissolution of Pd in a locally acidic environment, increases the activity, and steers the reaction pathway toward propylene glycol. Rh-doped Pd further improves propylene glycol selectivity. Density functional theory (DFT) suggests that the Rh dopant lowers the energy associated with the production of the final intermediate in propylene glycol formation and renders the desorption step spontaneous, a concept consistent with experimental studies. We report a 75% faradic efficiency toward propylene glycol maintained over 100 h of operation.

Gut microbiota regulate stress resistance by influencing microglia-neuron interactions in the hippocampus.

Communication among the brain, gut and microbiota in the gut is known to affect the susceptibility to stress, but the mechanisms involved are unclear. Here we demonstrated that stress resistance in mice was associated with more abundant Lactobacillus and Akkermansia in the gut, but less abundant Bacteroides, Alloprevotella, Helicobacter, Lachnoclostridium, Blautia, Roseburia, Colidextibacter and Lachnospiraceae NK4A136. Stress-sensitive animals showed higher permeability and stronger immune responses in their colon, as well as higher levels of pro-inflammatory cytokines in serum. Their hippocampus also showed more extensive microglial activation, abnormal interactions between microglia and neurons, and lower synaptic plasticity. Transplanting fecal microbiota from stress-sensitive mice into naïve ones perturbed microglia-neuron interactions and impaired synaptic plasticity in the hippocampus, translating to more depression-like behavior after stress exposure. Conversely, transplanting fecal microbiota from stress-resistant mice into naïve ones protected microglia from activation and preserved synaptic plasticity in the hippocampus, leading to less depression-like behavior after stress exposure. These results suggested that gut microbiota may influence resilience to chronic psychological stress by regulating microglia-neuron interactions in the hippocampus.

ASAP: a platform for gene functional analysis in Angelica sinensis.

BACKGROUND: Angelica sinensis (Danggui), a renowned medicinal orchid, has gained significant recognition for its therapeutic effects in treating a wide range of ailments. Genome information serves as a valuable resource, enabling researchers to gain a deeper understanding of gene function. In recent times, the availability of chromosome-level genomes for A. sinensis has opened up vast opportunities for exploring gene functionality. Integrating multiomics data can allow researchers to unravel the intricate mechanisms underlying gene function in A. sinensis and further enhance our knowledge of its medicinal properties. RESULTS: In this study, we utilized genomic and transcriptomic data to construct a coexpression network for A. sinensis. To annotate genes, we aligned them with sequences from various databases, such as the NR, TAIR, trEMBL, UniProt, and SwissProt databases. For GO and KEGG annotations, we employed InterProScan and GhostKOALA software. Additionally, gene families were predicted using iTAK, HMMER, OrholoFinder, and KEGG annotation. To facilitate gene functional analysis in A. sinensis, we developed a comprehensive platform that integrates genomic and transcriptomic data with processed functional annotations. The platform includes several tools, such as BLAST, GSEA, Heatmap, JBrowse, and Sequence Extraction. This integrated resource and approach will enable researchers to explore the functional aspects of genes in A. sinensis more effectively. CONCLUSION: We developed a platform, named ASAP, to facilitate gene functional analysis in A. sinensis. ASAP ( www.gzybioinformatics.cn/ASAP ) offers a comprehensive collection of genome data, transcriptome resources, and analysis tools. This platform serves as a valuable resource for researchers conducting gene functional research in their projects, providing them with the necessary data and tools to enhance their studies.

Risk factors for new renal scarring in children with vesicoureteral reflux receiving continuous antibiotic prophylaxis.

To investigate the risk factors for new renal scarring (NRS) in children with vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). This was a single-center cohort study. The clinical data of 140 children with grade I-V VUR receiving CAP were analyzed. In this study, exposure variables were sex, younger age at the initial diagnosis of UTI ≤ 12 months, the occurrence of breakthrough urinary tract infection (BT-UTI), high-grade VUR, bilateral VUR, etiology, presence of renal scarring at the initial diagnosis and ultrasound abnormalities. The outcome was NRS. A total of 140 children were included in the risk factor analysis of NRS, 73 of whom experienced NRS, an incidence rate of 52.14%. Multivariate Cox regression suggested that the presence of renal function impairment after the initial diagnosis of UTI (OR 3.411, 95% CI 1.5751-6.646) and the occurrence of BT-UTI while receiving CAP (OR 1.995, 95% CI 1.089-2.958) were independent risk factors for NRS. Multivariate Cox regression showed that high-grade VUR had no significant effects on NRS (OR 0.940, 95% CI 0.462-1.912, P = 0.864). No significant difference was identified in multivariate Cox regression analysis in the IV-V group (vs I-III group) (OR 0.960, 95% CI 0.565-1.633, P = 0.960). Renal function impairment after the initial diagnosis of UTI and the occurrence of BT-UTI while receiving CAP were independent risk factors for NRS. Neither univariate analysis nor multivariate analysis found a correlation between VUR grade and NRS.