Using satellite data on remote transportation of air pollutants for PM2.5 prediction in northern Taiwan.

Accurate PM2.5 prediction is part of the fight against air pollution that helps governments to manage environmental policy. Satellite Remote sensing aerosol optical depth (AOD) processed by The Multi-Angle Implementation of Atmospheric Correlation (MAIAC) algorithm allows us to observe the transportation of remote pollutants between regions. The paper proposes a composite neural network model, the Remote Transported Pollutants (RTP) model, for such long-range pollutant transportation that predicts more accurate local PM2.5 concentrations given such satellite data. The proposed RTP model integrates several deep learning components and learns from the heterogeneous features of various domains. We also detected remote transportation pollution events (RTPEs) at two reference sites from the AOD data. Extensive experiments using real-world data show that the proposed RTP model outperforms the base model that does not account for RTPEs by 17%-30%, 23%-26% and 18%-22% and state-of-the-art models that account for RTPEs by 12%-22%, 12%-14%, and 10%-11% at +4h to +24h, +28h to +48 hours, and +52h to +72h hours respectively.

Metastasis suppressor 1 interacts with protein tyrosine phosphatase receptor-δ to regulate adipogenesis.

Adipogenesis is a finely controlled process and its dysfunction may contribute to metabolic disorders such as obesity. Metastasis suppressor 1 (MTSS1) is a player in tumorigenesis and metastasis of various types of cancers. To date, it is not known whether and how MTSS1 plays a role in adipocyte differentiation. In the current study, we found that MTSS1 was upregulated during adipogenic differentiation of established mesenchymal cell lines and primary cultured bone marrow stromal cells. Gain-of-function and loss-of-function experiments uncovered that MTSS1 facilitated adipocyte differentiation from mesenchymal progenitor cells. Mechanistic explorations revealed that MTSS1 bound and interacted with FYN, a member of Src family of tyrosine kinases (SFKs), and protein tyrosine phosphatase receptor-δ (PTPRD). We demonstrated that PTPRD was capable of inducing the differentiation of adipocytes. Overexpression of PTPRD attenuated the impaired adipogenesis induced by the siRNA targeting MTSS1. Both MTSS1 and PTPRD activated SFKs by suppressing the phosphorylation of SFKs at Tyr530 and inducing the phosphorylation of FYN at Tyr419. Further investigation showed that MTSS1 and PTPRD were able to activate FYN. Collectively, our study has for the first time unraveled that MTSS1 plays a role in adipocyte differentiation in vitro through interacting with PTPRD and thereby activating SFKs such as FYN tyrosine kinase.

Tandem Oxidative Ritter Reaction/Hydration/Aldol Condensation of α-Arylketones with Propiolonitriles for the Construction of 3-Acyl-3-pyrrolin-2-ones.

A novel tandem oxidative Ritter reaction/hydration/aldol condensation of α-arylketones with substituted propiolonitriles has been developed. This protocol conveniently affords a wide range of functionalized 3-acyl-3-pyrrolin-2-ones through the efficient construction of four chemical bonds, a C-N bond, a C═C bond, and two C═O bonds, and the formation of one ring bearing an aza-quaternary center, which is ascribed to the strategical introduction of functionalized nitriles to this transformation. A reaction mechanism was proposed based on some control experiments.

Insights into the biosynthesis of septacidin l-heptosamine moiety unveils a VOC family sugar epimerase.

l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4'-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 (2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4'-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4'-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 (3). An interesting phenomenon is that the SEP intermediates with 4'-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.

Nocardia cyriacigeorgica infection in a patient with repeated fever and CD4+ T cell deficiency: A case report.

BACKGROUND: Nocardia pneumonia shares similar imaging and clinical features with pulmonary tuberculosis and lung neoplasms, but the treatment and anti-infective medication are completely different. Here, we report a case of pulmonary nocardiosis caused by Nocardia cyriacigeorgica (N. cyriacigeorgica), which was misdiagnosed as community-acquired pneumonia (CAP) with repeated fever. CASE SUMMARY: A 55-year-old female was diagnosed with community-acquired pneumonia in the local hospital because of repeated fever and chest pain for two months. After the anti-infection treatment failed in the local hospital, the patient came to our hospital for further treatment. Enhanced computed tomography showed multiple patchy, nodular and strip-shaped high-density shadows in both lungs. A routine haematological examination was performed and showed abnormalities in CD19+ B cells and CD4+ T cells. Positive acid-fast bifurcating filaments and branching gram-positive rods were observed in the bronchoalveolar lavage fluid of the patient under an oil microscope, which was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry as N. cyriacigeorgica. The patient's condition quickly improved after taking 0.96 g compound sulfamethoxazole tablets three times a day. CONCLUSION: The antibiotic treatment of Nocardia pneumonia is different from that of common CAP. Attention should be given to the pathogenic examination results of patients with recurrent fever. Nocardia pneumonia is an opportunistic infection. Patients with CD4+ T-cell deficiency should be aware of Nocardia infection.

Schizophrenia and oxidative stress from the perspective of bibliometric analysis.

Background: A growing number of studies has implicated oxidative stress in the pathophysiology of psychiatric disorders including schizophrenia. The aim of this study was to explore the field of schizophrenia and oxidative stress-related research from a bibliometric perspective. Methods: All relevant publications on schizophrenia and oxidative stress were obtained from Web of Science Core Collection (WOSCC) database from its inception date to November 8, 2022. VOSviewer software was used to examine co-authorships and co-occurring keywords. R software was used to present the main characteristics of publications and cooperation frequency among countries. CiteSpace was used to investigate keywords with the strongest citation bursts. Results: A total of 3,510 publications on schizophrenia and oxidative stress were included. The United States had the largest number of publications (26.1%), and international collaborations. University of Melbourne was the most productive institution, while Schizophrenia Research was the most productive journal in this field. Apart from "schizophrenia" and "oxidative stress", the terms "prefrontal cortex", "brain" and "nitric oxide" were among the most frequently used keywords. Conclusions: In conclusion, research on the association between oxidative stress and schizophrenia has received growing attention in the academic literature that is expected to continue its upward trajectory during the next two decades. Existing research suggests there has been a transition from research focused on pathways to animal models, and subsequently to clinical applications. Intervention studies on oxidative stress and schizophrenia are likely to be an important focus of related work in the near future.

Characterization of three succinyl-CoA acyltransferases involved in polyketide chain assembly.

Polyketides are a class of natural products with astonishing structural diversities, fascinating biological activities, and a versatile of applications. In polyketides biosynthesis, acyltransferases (ATs) are the 'gatekeeping' enzymes selecting the specific CoA-activated acyl groups as building blocks and transferring them onto the phosphopantetheine arm of acyl carrier proteins (ACPs) to enable the following condensation reactions to assemble the polyketide chain. Herein, the Art2 protein from aurantinins, a group of the antibacterial polyketides, is characterized in vitro as an AT that can load a CoA-activated succinyl unit onto the first ACP domain of Art17 (ACPArt17-1). In addition, another two proteins, GbnB and EtnB, involved in the biosynthesis of gladiolin and etnangien respectively, were traced by literature mining, homologous searching, and product structure analysis and then identified as functional succinyl-CoA ATs by the ACPArt17-1 assays. Taken together, by the assay method employing ACPArt17-1 as an acyl acceptor, we identified three ATs that can introduce a succinyl unit into the polyketide assembly line, which enriches the toolbox of polyketide biosynthetic enzymes and sets a stage for incorporating a succinyl unit into polyketide backbones in synthetic biological manners. KEY POINTS: • Three acyltransferases that are able to load ACP with a succinyl unit were characterized in vitro. • ACPArt17-1 can be used as an acceptor to assay succinyl-CoA AT from different polyketides. • The succinyl unit can be incorporated into polyketides assembly process.

Removing unreacted amino groups in graphitic carbon nitride through residual heating to improve the photocatalytic performance.

In most of the research about graphitic carbon nitride (g-C3N4), g-C3N4 is prepared through the calcination of nitrogen-rich precursors. However, such a preparation method is time-consuming, and the photocatalytic performance of pristine g-C3N4 is lackluster due to the unreacted amino groups on the surface of g-C3N4. Therefore, a modified preparation method, calcination through residual heating, was developed to achieve rapid preparation and thermal exfoliation of g-C3N4 simultaneously. Compared with pristine g-C3N4, the samples prepared by residual heating had fewer residual amino groups, a thinner 2D structure, and higher crystallinity, which led to a better photocatalytic performance. The photocatalytic degradation rate of the optimal sample for rhodamine B could reach 7.8 times higher than that of pristine g-C3N4.

Recent Advances on Transition-Metal-Based Layered Double Hydroxides Nanosheets for Electrocatalytic Energy Conversion.

Transition-metal-based layered double hydroxides (TM-LDHs) nanosheets are promising electrocatalysts in the renewable electrochemical energy conversion system, which are regarded as alternatives to noble metal-based materials. In this review, recent advances on effective and facile strategies to rationally design TM-LDHs nanosheets as electrocatalysts, such as increasing the number of active sties, improving the utilization of active sites (atomic-scale catalysts), modulating the electron configurations, and controlling the lattice facets, are summarized and compared. Then, the utilization of these fabricated TM-LDHs nanosheets for oxygen evolution reaction, hydrogen evolution reaction, urea oxidation reaction, nitrogen reduction reaction, small molecule oxidations, and biomass derivatives upgrading is articulated through systematically discussing the corresponding fundamental design principles and reaction mechanism. Finally, the existing challenges in increasing the density of catalytically active sites and future prospects of TM-LDHs nanosheets-based electrocatalysts in each application are also commented.

Pathogenic mechanisms of glucocorticoid-induced osteoporosis.

Glucocorticoid (GC) is one of the most prescribed medicines to treat various inflammatory and autoimmune diseases. However, high doses and long-term use of GCs lead to multiple adverse effects, particularly glucocorticoid-induced osteoporosis (GIO). Excessive GCs exert detrimental effects on bone cells, including osteoblasts, osteoclasts, and osteocytes, leading to impaired bone formation and resorption. The actions of exogenous GCs are considered to be strongly cell-type and dose dependent. GC excess inhibits the proliferation and differentiation of osteoblasts and enhances the apoptosis of osteoblasts and osteocytes, eventually contributing to reduced bone formation. Effects of GC excess on osteoclasts mainly include enhanced osteoclastogenesis, increased lifespan and number of mature osteoclasts, and diminished osteoclast apoptosis, which result in increased bone resorption. Furthermore, GCs have an impact on the secretion of bone cells, subsequently disturbing the process of osteoblastogenesis and osteoclastogenesis. This review provides timely update and summary of recent discoveries in the field of GIO, with a particular focus on the effects of exogenous GCs on bone cells and the crosstalk among them under GC excess.

Influence of land-sea breeze on PM[Formula: see text] prediction in central and southern Taiwan using composite neural network.

PM[Formula: see text] prediction plays an important role for governments in establishing policies to control the emission of excessive atmospheric pollutants to protect the health of citizens. However, traditional machine learning methods that use data collected from ground-level monitoring stations have reached their limit with poor model generalization and insufficient data. We propose a composite neural network trained with aerosol optical depth (AOD) and weather data collected from satellites, as well as interpolated ocean wind features. We investigate the model outputs of different components of the composite neural network, concluding that the proposed composite neural network architecture yields significant improvements in overall performance compared to each component and the ensemble model benchmarks. The monthly analysis also demonstrates the superiority of the proposed architecture for stations where land-sea breezes frequently occur in the southern and central Taiwan in the months when land-sea breeze dominates the accumulation of PM[Formula: see text].

Narirutin activates TFEB (transcription factor EB) to protect against Acetaminophen-induced liver injury by targeting PPP3/calcineurin.

Acetaminophen (APAP) overdose is the predominant cause of drug-induced liver injury worldwide. The macroautophagy/autophagy-lysosomal pathway (ALP) is involved in the APAP hepatotoxicity. TFEB (transcription factor EB) promotes the expression of genes related to autophagy and lysosomal biogenesis, thus, pharmacological activation of TFEB-mediated ALP may be an effective therapeutic approach for treating APAP-induced liver injury. We aimed to reveal the effects of narirutin (NR), the main bioactive constituents isolated from citrus peels, on APAP hepatotoxicity and to explore its underlying mechanism. Administration of NR enhanced activities of antioxidant enzymes, improved mitochondrial dysfunction and alleviated liver injury in APAP-treated mice, whereas NR did not affect APAP metabolism and MAPK/JNK activation. NR enhanced TFEB transcriptional activity and activated ALP in an MTOR complex 1 (MTORC1)-independent but PPP3/calcineurin-dependent manner. Moreover, knockout of Tfeb or knockdown of PPP3CB/CNA2 (protein phosphatase 3, catalytic subunit, beta isoform) in the liver abolished the beneficial effects of NR on APAP overdose. Mechanistically, NR bound to PPP3CB via PRO31, LYS61 and PRO347 residues and enhanced PPP3/calcineurin activity, thereby eliciting dephosphorylation of TFEB and promoting ALP, which alleviated APAP-induced oxidative stress and liver injury. Together, NR protects against APAP-induced liver injury by activating a PPP3/calcineurin-TFEB-ALP axis, indicating NR may be a potential agent for treating APAP overdose.Abbreviations: ALP: autophagy-lysosomal pathway; APAP: acetaminophen; APAP-AD: APAP-protein adducts; APAP-Cys: acetaminophen-cysteine adducts; CAT: catalase; CETSA: cellular thermal shift assay; CQ: chloroquine; CYP2E1: cytochrome P450, family 2, subfamily e, polypeptide 1; CYCS/Cyt c: cytochrome c, somatic; DARTS: drug affinity responsive target stability assay; ENGASE/NAG: endo-beta-N-acetylglucosaminidase; GOT1/AST: glutamic-oxaloacetic transaminase 1, soluble; GPT/ALT: glutamic pyruvic transaminase, soluble; GSH: glutathione; GPX/GSH-Px: glutathione peroxidase; KD: dissociation constant; Leu: leupeptin; MCOLN1: mucolipin 1; MTORC1: MTOR complex 1; NAC: N-acetylcysteine; NAPQI: N-acetyl-p-benzoquinoneimine; NFAT: nuclear factor of activated T cells; NR: narirutin; OA: okadaic acid; RRAG: Ras related GTP binding; ROS: reactive oxygen species; PPP3CB/CNA2: protein phosphatase 3, catalytic subunit, beta isoform; PPP3R1/CNB1: protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type I); SOD: superoxide dismutase; SPR: surface plasmon resonance analysis; TFEB: transcription factor EB.

Glucose-induced enhanced anti-oxidant activity inhibits apoptosis in goose fatty liver.

The development of mammalian nonalcoholic fatty liver disease is associated with oxidative stress, reduced mitochondrial function, and increased apoptosis in hepatocytes; however, the expressions of mitochondria-related genes are elevated in goose fatty liver, suggesting that there may be a unique protective mechanism in goose fatty liver. The aim of the study was to investigate this protective mechanism in terms of anti-oxidant capacity. Our data showed no substantial differences in the mRNA expression levels of the apoptosis-related genes including B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax), cysteinyl aspartate-specific proteinase-3 (Caspase-3), and cysteinyl aspartate-specific proteinase-9 (Caspase-9) in the livers of the control and overfeeding Lander geese groups. The protein expression levels of Caspase-3 and cleaved Caspase-9 were not markedly different between the groups. Compared with the control group, malondialdehyde content was significantly lower (P < 0.01), glutathione peroxidase (GSH-Px) activity, glutathione (GSH) content, and mitochondrial membrane potential levels were higher (P < 0.01) in the overfeeding group. The mRNA expression levels of the anti-oxidant genes superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), and glutathione peroxidase 2 (GPX2) were increased in goose primary hepatocytes after 40 mM and 60 mM glucose treatment. Reactive oxygen species (ROS) levels were significantly reduced (P < 0.01), whereas the mitochondrial membrane potential was maintained at normal levels. The mRNA expression levels of the apoptosis-related genes Bcl-2, Bax, and Caspase-3 were not substantial. There were no significant differences in the expression levels of Caspase-3 and cleaved Caspase-9 proteins. In conclusion, glucose-induced enhanced anti-oxidant capacity may help protect the function of mitochondria and inhibit the occurrence of apoptosis in goose fatty liver.

No significant pathological symptoms were observed in the liver of goose after overfeeding, suggesting that a specific protection mechanism exists in goose liver. Previous studies have shown that mitochondria may participate in the formation of goose fatty liver by improving its energy metabolism and the production of precursor metabolites. To further understand the role of mitochondria in the formation of goose fatty liver, the present study investigated the changes of mitochondrial function, anti-oxidant capacity, and apoptosis in goose fatty liver. There were found that the level of mitochondrial membrane potential was increased, no apoptosis was observed and anti-oxidant capacity was improved in goose fatty liver, no apoptosis was observed and anti-oxidant genes expressions were increased in goose primary hepatocytes after 40 mM glucose treatment. Our findings imply that apoptosis is inhibited by glucose-induced enhanced anti-oxidant activity in goose fatty liver. Our study not only contributes to revealing the protective mechanism in goose fatty liver but also providing new references for the study of nonalcoholic fatty liver in mammals.

The protection of luteolin against diabetic cardiomyopathy in rats is related to reversing JNK-suppressed autophagy.

Increasing evidence has shown that impaired autophagy dramatically causes myocardial hypertrophy and fibrosis in the diabetic heart, ultimately leading to diabetic cardiomyopathy (DCM). Luteolin has been reported to effectively attenuate diabetic cardiovascular injury by inhibiting oxidative stress and alleviate sepsis-induced myocardial injury by enhancing autophagy. However, whether luteolin can reduce DCM through activating autophagy and the underlying mechanism remain unclear. Here, reversing the c-Jun N-terminal kinase (JNK)-suppressed autophagy pathway by which luteolin attenuates DCM was explored. Male Sprague-Dawley rats were injected with streptozotocin to induce diabetes. After 6 weeks of diabetes, rats were treated with luteolin (50, 100 and 200 mg kg-1, i.g.) for 4 weeks. Histological and functional alterations in the diabetic heart were determined using HE staining, Masson staining and echocardiography. The expressions of myocardial miR-221, JNK, and c-Jun and autophagic vesicles in diabetes were evaluated by quantitative PCR, Western blotting and electron microscopy. Luteolin significantly improved cardiac function and attenuated myocardial disorganization and fibrosis in the diabetic rat accompanying the dose-dependent down-regulation of JNK, c-Jun, miR-221 and p62, increase of LC3-II/I and autophagic vesicles, and decrease of mitochondrial swelling in the diabetic heart. These data suggest that the protection of luteolin against DCM, at least, is related to suppressing JNK/c-Jun-regulated miR-221 and the subsequent blockage of autophagy.

Interaction between Changan Granule and its main components in the plasma and CYP450 enzymes.

ETHNOPHARMACOLOGICAL RELEVANCE: Changan Granule (CAG) is a Chinese patent drug developed based on an empirical prescription in accordance with the formulation theory of Traditional Chinese Medicine. The prescription is composed of eight herbal drugs which have been traditionally used by Chinese people for a long history. It has effects of invigorating spleen and supplementing qi, as well as regulating liver and ceasing diarrhea, and is indicated for the treatment of irritable bowel syndrome (IBS). AIM OF THE STUDY: This study was aimed to investigate the interaction between CAG and its main components and cytochrome P450 (CYP450) enzymes so as to characterize the major metabolites and metabolic enzymes and evaluate the safety concerns to its clinical use. MATERIALS AND METHODS: Both in vivo and in vitro experiments using such as diarrhea-predominant IBS (IBS-D) rat model, HepG2 cells, and human liver microsomes (HLM) were carried out to investigate the interaction between CAG and its main components and CYP450 enzymes. Real-time quantitative PCR (qPCR), ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and cocktail probes were employed to qualitatively or quantitatively measure the metabolites and metabolic enzymes. RESULTS: CAG inhibited the enzyme activities of CYP1A2, CYP2E1, CYP2D6, CYP2C9, and CYP3A4 and the mRNA expressions of CYP2E1, CYP2C9, CYP3A4, and CYP2D6 in vitro. CAG down-regulated the increased expression of CYP1A2 and up-regulated the decreased expression of CYP3A1 in vivo. Twenty-two metabolites were characterized from the main components of CAG after incubation with HLM in vitro. CYP2D6, CYP2E1, CYP3A4 and CYP2C9 were identified as the characteristic metabolic enzymes. CONCLUSIONS: This study provides a reference for clinical application of CAG in safety. CAG and CYP450 enzymes are interacted. CAG is mainly metabolized by CYP2E1 and CYP2D6. The expression of CYP2E1 and CYP2D6 are more susceptible to be influenced by CAG in comparison with that of CYP3A4, CYP2C9 and CYP1A2. It implies the potential risk of interaction when CAG is taken together with the drugs metabolized by CYP2E1 and CYP2D6.

Massive secretions in paragonimiasis pleural effusion: a new finding concerning clinical recognition and treatment.

Some paragonimiasis patients in Chongqing, southwest China, have recently exhibited pleural effusions (PEs) with massive viscous secretions. This study aimed to investigate their clinical characteristics, thereby promoting effective treatments. A 3-year retrospective review of paragonimiasis patients who were admitted for nonhomogeneous PEs at Chongqing University Three Gorges Hospital was conducted. Epidemiological data, symptoms, laboratory and imaging findings, treatments, and outcomes were analyzed. Twenty-eight patients were identified, of which 22 (78.6%) were males and 22 (78.6%) were rural residents. Respiratory (85.7%) and constitutional (57.1%) symptoms were common. Paragonimus-specific ELISA was positive in all patients. Eosinophilia was detected in all patients in peripheral blood and PEs. Irregular hyperdense signals were observed in PEs by chest CT scans (96.4%) and ultrasonography (100.0%). Thoracic closed drainage failed in 10 patients (conservative group) because of tube blockage and was eventually replaced by video-assisted thoracoscopic surgery (VATS). Eighteen patients (surgery group) initially underwent VATS, or thoracotomy surgery, without complications. Massive secretions, described as "bean-dregs" or "egg-floccule," were detected intraoperatively, which explained the imaging findings and tube blockage. All patients recovered well after 2-3 courses of postoperative praziquantel treatment. Viscous secretions in paragonimiasis patients warrant great concern. Irregular hyperdense signals in effusions are important characteristics in CT scans and ultrasonography. Treatments such as thoracic closed drainage may fail due to viscous secretions blocking the tube; therefore, surgeries should be considered. In-depth multidisciplinary research may help determine the optimal treatment strategy and reveal the origin of these secretions.

Oridonin employs interleukin 1 receptor type 2 to treat noise-induced hearing loss by blocking inner ear inflammation.

NOD-like receptor protein 3 (NLRP3) inflammasomes trigger the inflammatory cascades and participate in various inflammatory diseases, including noise-induced hearing loss (NIHL) caused by oxidative stress. Recently, the anti-inflammatory traditional medicine oridonin (Ori) has been reported to provide hearing protection in mice after noise exposure by blocking the NLRP3-never in mitosis gene A-related kinase 7 (NEK7)-inflammasome complex assembly. Using RNA sequencing analysis, we further elucidated that interleukin 1 receptor type 2 (IL1R2) may be another crucial factor regulated by Ori to protect NIHL. We observed that IL1R2 expression was localized in spiral ganglion neurons, inner and outer hair cells, in Ori-treated mouse cochleae. Additionally, we confirmed that ectopic overexpression of IL1R2 in the inner ears of healthy mice using an adeno-associated virus delivery system significantly reduced noise-induced ribbon synapse lesions and hearing loss by blocking the "cytokine storm" in the inner ear. This study provides a novel theoretical foundation for guiding the clinical treatment of NIHL.

DSS-induced acute colitis causes dysregulated tryptophan metabolism in brain: an involvement of gut microbiota.

Inflammatory bowel disease can cause pathological changes of certain organs, including the gut and brain. As the major degradation route of tryptophan (Trp), Kynurenine (Kyn) pathway are involved in multiple pathologies of brain. This study sought to explore the effects of Dextran sulphate sodium (DSS)-induced colitis on serum and brain Trp metabolism (especially the Kyn pathway) and its mechanisms. We induced acute colitis and sub-chronic colitis with 3% DSS and 1% DSS respectively and found more severe intestinal symptoms in acute colitis than sub-chronic colitis. Both of the colitis groups altered Trp-Kyn-Kynurenic acid (Kyna) pathway in serum by regulating the expression of rate-limiting enzyme (IDO-1, KAT2). Interestingly, only 3% DSS group activated Trp-Kyn pathway under the action of metabolic enzymes (IDO-1, TDO-2 and KAT2) in brain. Furthermore, intestinal flora 16S rRNA sequencing showed significantly changes in both DSS-induced colitis groups, including microbial diversity, indicator species, and the abundance of intestinal microflora related to Trp metabolism. The functional pathways of microbiomes involved in inflammation and Trp biosynthesis were elevated after DSS treatment. Moreover, correlation analysis showed a significant association between intestinal flora and Trp metabolism (both in serum and brain). In conclusion, our study suggests that DSS-induced acute colitis causes dysregulation of Trp-Kyn-Kyna pathways of Trp metabolism in serum and brain by affecting rate-limiting enzymes and intestinal flora.

Tanshinone IIA Inhibits Triple-Negative Breast Cancer Cells MDA-MB-231 via G Protein-Coupled Estrogen Receptor- (GPER-) Dependent Signaling Pathway.

Due to the lack of classic estrogen receptors, there has been a shortage of targeted therapy for triple-negative breast cancer (TNBC), resulting in a poor prognosis. However, the newly discovered G protein-coupled estrogen receptor (GPER) has been found to be expressed in TNBC cells. Salvia miltiorrhiza (Danshen) is an essential Chinese medicine for gynecological disorders, and its component tanshinone IIA (Tan IIA) exerts an anticancer effect. Therefore, this study attempted to investigate whether GPER is involved in the inhibitory effect of Tan IIA on TNBC. We applied various databases and GO pathway analysis to predict the possible mechanism of Tan IIA. We identified 39 overlapping targets, including c-Jun, c-Fos, and caspase-3, and enriched cell cycle-related pathways. Next, we demonstrated the strong binding ability of Tan IIA to GPER by molecular docking assay. In the subsequent validation tests, Cell Counting Kit-8 (CCK8) assay showed that Tan IIA inhibited proliferation of MDA-MB-231 cells time and dose dependently without affecting normal cells. Using Transwell plate, flow cytometry, and Western blot assays, we showed that Tan IIA inhibited migration and induced apoptosis of MDA-MB-231 dose dependently. Importantly, protein expressions of GPER, epidermal growth factor receptor (EGFR), extracellular regulated protein kinases (ERK), c-Fos, and c-Jun were all decreased by Tan IIA dose dependently. Administration of GPER inhibitor partly abolished these effects. Furthermore, nuclear translocation of c-Fos and c-Jun as well as cell cycle-related proteins was downregulated by Tan IIA dose dependently. In summary, Tan IIA could inhibit the proliferation and migration of MDA-MB-231 cells and induce apoptosis, and the possible mechanism may be the regulation of GPER-mediated pathways, suggesting that GPER could be a therapeutic target for TNBC.

Genome-Wide Identification of BES1 Gene Family in Six Cucurbitaceae Species and Its Expression Analysis in Cucurbita moschata.

The BES1 (BRI1-EMSSUPPRESSOR1) gene family play a vital role in the BR (brassinosteroid) signaling pathway, which is involved in the growth and development, biotic, abiotic, and hormone stress response in many plants. However, there are few reports of BES1 in Cucurbita moschata. In this study, 50 BES1 genes were identified in six Cucurbitaceae species by genome-wide analysis, which could be classified into 3 groups according to their gene structural features and motif compositions, and 13 CmoBES1 genes in Cucurbita moschata were mapped on 10 chromosomes. Quantitative real-time PCR analysis showed that the CmoBES1 genes displayed differential expression under different abiotic stress and hormone treatments. Subcellular localization showed that the most of CmoBES1 proteins localized in nucleus and cytoplasm, and transactivation assay indicated 9 CmoBES1 proteins played roles as transcription factors. Our analysis of BES1s diversity, localization, and expression in Curcubitaceae contributes to the better understanding of the essential roles of these transcription factors in plants.