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Abstract Hyperuricemic nephropathy (HN) is renal injury caused by hyperuricemia (HUA). While sleeve gastrectomy (SG) has shown promise in improving renal injury in patients with obesity-related HN, the mechanisms are not fully understood. This study induced an obesity-combined HN model in male ob/ob mice and measured serum uric acid (SUA), creatinine, and other biochemical indicators 6 weeks post-surgery. Renal histological changes were evaluated through staining techniques, and the study also assessed renal adenosine monophosphate-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation levels and urate transporter ABCG2 expression. In vitro experiments involved Nrf2 knockdown in AMPK-activated HK-2 cells and ChIP to confirm Nrf2 binding to the ABCG2 promoter. Results showed that SG reduced SUA levels, serum creatinine, and blood urea nitrogen, increased p-AMPK, p-Nrf2 protein, and ABCG2 expression, and alleviated renal fibrosis and inflammation. In vitro, Nrf2 knockdown down-regulated ABCG2 expression, and ChIP confirmed Nrf2’s role in ABCG2 transcription. The study suggests that SG may improve renal injury in HN mice by modulating the AMPK/Nrf2 pathway and upregulating ABCG2 transcription.

Abstract Thalamic brain areas play an important role in adaptive behaviors. Nevertheless, the population dynamics of thalamic relays during learning across sensory modalities remain unknown. Using a cross-modal sensory reward-associative learning paradigm combined with deep brain two-photon calcium imaging of large populations of auditory thalamus (medial geniculate body, MGB) neurons in male mice, we identified that MGB neurons are biased towards reward predictors independent of modality. Additionally, functional classes of MGB neurons aligned with distinct task periods and behavioral outcomes, both dependent and independent of sensory modality. During non-sensory delay periods, MGB ensembles developed coherent neuronal representation as well as distinct co-activity network states reflecting predicted task outcome. These results demonstrate flexible cross-modal ensemble coding in auditory thalamus during adaptive learning and highlight its importance in brain-wide cross-modal computations during complex behavior.

The longissimus dorsi muscle of sheep was treated with cold plasma (CP) induced by dielectric barrier discharge (DBD) at different time points (6, 12, 24, 48, 72 and 120 h) after slaughter. By analyzing changes in the color, myoglobin content, fat oxidation, total sulfhydryl content and surface hydrophobicity of samples during postmortem cold storage, the effects of DBD-CP treatment at different time points after slaughter on the color and oxidation stability of mutton at different time points after slaughter were determined. The results showed that DBD-CP treatment at different time points after slaughter had no significant effects on L* or a* values of mutton (P > 0.05), but significantly increased the b* value compared to the untreated control group (P 0.05). The thiobarbituric acid reactive substances (TBARS) value of the DBD-CP treatment group was higher than that of the control group (P < 0.05), and the treatment significantly reduced the total sulfhydryl content in mutton and increased the surface hydrophobicity (P < 0.05). In summary, DBD-CP treatment at 6 to 12 h after slaughter had the most significant effect on stabilizing and maintaining meat color. In addition, it could accelerate the oxidation of myofibrillar protein (MP). Therefore, DBD-CP treatment has potential application value in improving the quality of mutton.

Abstract Lipid droplets (LDs), which are active organelles, derive from the monolayer membrane of the endoplasmic reticulum and encapsulate neutral lipids internally. LD-associated proteins like RAB, those in the PLIN family, and those in the CIDE family participate in LD formation and development, and they are active players in various diseases, organelles, and metabolic processes (i.e., obesity, non-alcoholic fatty liver disease, and autophagy). Our synthesis on existing research includes insights from the formation of LDs to their mechanisms of action, to provide an overview needed for advancing research into metabolic diseases and lipid metabolism.

Abstract Individuals with autism spectrum disorder (ASD) have a higher prevalence of social memory impairment. A series of our previous studies revealed that hippocampal ventral CA1 (vCA1) neurons possess social memory engram and that the neurophysiological representation of social memory in the vCA1 neurons is disrupted in ASD-associated Shank3 knockout mice. However, whether the dysfunction of Shank3 in vCA1 causes the social memory impairment observed in ASD remains unclear. In this study, we found that vCA1-specific Shank3 conditional knockout (cKO) by the adeno-associated virus (AAV)- or specialized extracellular vesicle (EV)- mediated in vivo gene editing was sufficient to recapitulate the social memory impairment in male mice. Furthermore, the utilization of EV-mediated Shank3-cKO allowed us to quantitatively examine the role of Shank3 in social memory. Our results suggested that there is a certain threshold for the proportion of Shank3-cKO neurons required for social memory disruption. Thus, our study provides insight into the population coding of social memory in vCA1, as well as the pathological mechanisms underlying social memory impairment in ASD.

Infection of Rift Valley fever virus (RVFV), a highly pathogenic mosquito-borne zoonotic virus, triggers severe inflammatory pathogenesis but the underlying mechanism of inflammation activation is currently unclear. Here, we report that the non-structural protein NSs of RVFV triggers mitochondrial damage to activate the NLRP3 inflammasome leading to viral pathogenesis in vivo. It is found that the host transcription inhibition effect of NSs causes rapid down-regulation of myeloid cell leukemia-1(MCL-1), a pro-survival member of the Bcl-2 (B-cell lymphoma protein 2) protein family. MCL-1 down-regulation led to BAK activation in the mitochondria, which triggered mtROS production and release of oxidized mitochondrial DNA (ox-mtDNA) into the cytosol. Cytosolic ox-mtDNA binds and activates the NLRP3 inflammasome triggering NLRP3-GSDMD pyroptosis in RVFV infected cells. A NSs mutant virus (RVFV-NSsRM) that is compromised in inducing transcription inhibition did not trigger MCL-1 down-regulation nor NLRP3-GSDMD pyroptosis. RVFV infection of the Nlrp3-/- mouse model demonstrated that the RVFV-triggered NLRP3 pyroptosis contributed to RVFV inflammatory pathogenesis and fatal infection in vivo. Infection with the RVFV-NSsRM mutant virus similarly showed alleviated inflammatory pathogenesis and reduced fatality rate. Taken together, these results revealed a mechanism by which a virulence factor activates the mitochondrial MCL-1-BAK axis through inducing host transcription inhibition to trigger NLRP3-dependent inflammatory pathogenesis.

In a harsh geological environment, different geo-disasters might co-occur or be in a chain sequence. Currently, existing research in related fields documents numerous instances of disaster chains and responses, which provided this study with important materials for determining disaster chains probability and summarized the disaster prevention and mitigation (DPM) mode. In this study, through the depth of the geo-disaster chains cases and the DPM cases, enabled a mitigation mode analysis summary. We take the case of geo-disaster chains as an example for this study, and represent 20 typical geo-disaster chains by data fusion and structuring of 139 geo-disaster chains cases.The probability assessment of geo-disaster chains is crucial for risk management and regional resilience. We introduced a Bayesian network (BN) model to describe the process of geo-disaster chains formation to map the structure and assess the joint probability of geo-disaster chains. The BN results showed that the longer the disaster chains length, the smaller the probability of the chains occurring. Among these, the probability of “Collapses-landslides-debris flows–barrier lakes–flash floods” is the lowest (0.069). Through sensitivity analysis, it is found that precipitation is the most sensitive factor in the development of geo-disaster. Interpretive structural modeling (ISM) is employed to examine the DPM index system across three key aspects: disaster emergency preparation, disaster response, and disaster recovery, and the conceptualized interaction among these components. ISM results showed that government policy intervention and scientific DPM measures can effectively reduce the losses caused by the development of geo-disaster chains. This research combined the occurrence process of the disaster chains with the disaster response process, and determined the entire chains of characterization from disaster understanding to disaster response, and helped reduce the vulnerabilities caused by disasters.

Forests emit a large amount of biogenic volatile organic compounds (BVOCs) in response to biotic and abiotic stress. Despite frequent occurrence of large forest fires in recent years, the impact of smoke stress derived from these forest fires on the emission of BVOCs is largely unexplored. Thus, the aims of the study were to quantify the amount and composition of BVOCs released by two sub-tropical tree species, Cunninghamia lanceolata and Schima superba, in response to exposure to smoke. Physiological responses and their relationship with BVOCs were also investigated. The results showed that smoke treatments significantly (p < 0.001) promoted short-term release of BVOCs by C. lanceolata leaves than S. superba; and alkanes, olefins and benzene homologs were identified as major classes of BVOCs. Both C. lanceolata and S. superba seedlings showed significant (p < 0.005) physiological responses after being smoke-stressed where photosynthetic rate remained unaffected, chlorophyll content greatly reduced and Activities of anti-oxidant enzymes and the malondialdehyde content generally increased with the increase in smoke concentration. Activities of anti-oxidant enzymes showed mainly positive correlations with the major BVOCs. In conclusion, the release of BVOCs following smoke stress is species-specific and there exists a link between activities of antioxidant enzymes and BVOCs released. The findings provide insight about management of forest fires in order to control excessive emission of smoke that would trigger increased release of BVOCs.

Abstract Perception of fear induced by others in danger elicits complex vicarious fear responses and behavioral outputs. In rodents, observing a conspecific receive aversive stimuli leads to escape and freezing behavior. It remains unclear how these behavioral self-states in response to others in fear are neurophysiologically represented. Here, we assess such representations in the ventromedial prefrontal cortex (vmPFC), an essential site for empathy, in an observational fear (OF) paradigm in male mice. We classify the observer mouse’s stereotypic behaviors during OF using a machine-learning approach. Optogenetic inhibition of the vmPFC specifically disrupts OF-induced escape behavior. In vivo Ca2+ imaging reveals that vmPFC neural populations represent intermingled information of other- and self-states. Distinct subpopulations are activated and suppressed by others’ fear responses, simultaneously representing self-freezing states. This mixed selectivity requires inputs from the anterior cingulate cortex and the basolateral amygdala to regulate OF-induced escape behavior.

Abstract Background Decreased bioavailability of nitric oxide (NO) under hypoxic conditions can lead to endothelial dysfunction. NO supplementation may protect endothelial function in ischemia-reperfusion (IR) injury. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to verify the protective effect of NO donors on endothelium in IR injury. Methods Medline, Embase, Cochrane Library, and Web of Science databases were searched from inception to April 1, 2023. The specific inclusion criteria were as follows: (1) RCTs; (2) trials comparing NO donors with placebo control groups; and (3) trials reporting the effects of these interventions on vascular endothelial functional outcomes in IR injury. Random-effects models were used to assess pooled effect sizes, which were expressed as standardized mean differences (SMD). Results Seven studies satisfied the inclusion criteria and consisted of a total of 149 participants. NO donors were protective of endothelial function in IR injury (SMD: − 1.60; 95% confidence interval [CI]: − 2.33, − 0.88, P

To simulate the biomechanical changes of knee joint before and after wearing the orthosis in patients with knee osteoarthritis (KOA) by constructing a finite element model of the knee joint and a customized additively manufactured knee orthosis, so as to verify the decompression effect of the orthosis, and aimed at orthopaedics, a quantitative research on the therapeutic effect of knee orthosis was conducted to evaluate the clinical efficacy of knee orthosis.This experiment was approved by the Ethics Committee of the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. A woman with knee osteoarthritis was recruited, and the knee joint was subjected to optical body surface and CT scans. A custom-made additively manufactured knee orthosis was designed according to the principle of unilateral decompression. After boundary setting and other steps, software such as ANSYS was used to build a finite element model of the knee joint and a customized additively manufactured knee joint orthosis. By applying a compressive load of 1100 N to the knee joint along the direction of the lower limb load-bearing axis, a simulation and stress analysis was performed to study the deloading effect of a custom additively manufactured knee orthosis on the knee compartment. A finite element analysis of KOA characteristics was conducted for verification, considering the influence of cartilage, ligament, and lower limb skin on the bearing capacity of the knee joint. Compared with the case without wearing any orthosis, after wearing the customized knee orthosis, the varus angle of the knee joint was reduced, the medial pressure of the knee joint was shifted to the lateral side, and the pressure of the medial compartment of the knee joint was significantly reduced. The custom additively manufactured knee orthosis can reduce the pressure generated by the medial compartment of the knee joint during walking in patients with early and mid-stage medial compartment knee osteoarthritis, and the load reduction effect is significant.

AimsThe aim of this study was to analyze changes in emission of water-soluble ions in fine particulate matter over time and in different southwest forest areas in China based on China’s Forestry Statistical Yearbook and MODIS satellite fire point data.MethodsWe took 6 dominant tree species samples in the southwestern forest region of China and simulated combustion using controllable biomass combustion devices. Based on the spatial analysis method of ArcGIS, combining satellite fire point data and official statistical yearbooks, we analyzed the spatial and temporal dynamics of emissions of water-soluble ions in PM2.5 released by forest fires in southwestern forest areas from 2004 to 2021.ResultsThe total amount of forest biomass combusted in southwest forest areas was 64.43 kt. Among the different forest types, the proportion of burnt subtropical evergreen broad-leaved forest was the largest (60.49%) followed by subtropical mixed coniferous and broad-leaved forest (22.78%) and subtropical evergreen coniferous forest (16.72%). During the study period, 61.19 t of water-soluble ions were released in PM2.5 from forest fires, and the emissions of Li+, Na+, NH4+, K+, Mg2+, Ca2+, F−, Cl−, Br−, NO3−, PO43− and SO42− were 0.48 t, 11.54 t, 2.51 t, 19.44 t, 2.12 t, 2.92 t, 1.94 t, 12.70 t, 1.12 t, 1.18 t, 1.17 t and 4.07 t, respectively. Yunnan was the province with the highest emissions of water-soluble ions in PM2.5 in the southwest forest areas, and the concentration K+ was the highest. Emission of water-soluble ions in Yunnan and Sichuan all showed a significant downward trend, while the overall decrease in Tibet, Chongqing and Guizhou was not significant. The peak emission of water-soluble ions in PM2.5 during forest fires appeared in spring and winter, which accounted for 87.66% of the total emission.DiscussionThis study reveals the spatiotemporal changes in water-soluble ion emissions from forest fires, by studying the spatiotemporal dynamics of water-soluble ions in PM2.5, we can better understand the sources, distribution, and change patterns of these ions, as well as their impact on the atmospheric environment, ecosystems, and climate change. This information is crucial for predicting and managing air pollution, as well as developing effective forest management and environmental protection policies to respond to fires; and hence concerted fire prevention efforts should be made in each province, taking into account the season with higher probability of fire occurrence to reduce the potential impact of fire-related pollutions.

Abstract Background Misplacement of double-lumen endobronchial tubes (DLTs) during bronchial intubation, especially when bronchoscopy guidance is not applicable, threatens effective lung isolation and brings about airway injury during reposition. We aimed to examine whether a novel maneuver called right tracheal displacement (RTD) can reduce left-sided DLT misplacement during first-attempt intubation without bronchoscopy guidance. Methods Patients that underwent thoracic surgeries requiring one-lung ventilation during November 2020 to January 2021 were recruited and randomized into control and RTD group, with 54 cases in each group. The primary outcomes included the incidence of DLT misplacement and the time to complete desired bronchial intubation. The secondary outcomes included mucosal injury, sore throat and hoarseness upon emergence and at 24 h post-operatively. Result The incidence of DLT misplacement in RTD group was significantly lower compared to control group (0% vs. 16.7%) The time to complete bronchial intubation was also significantly shortened in RTD group compared to control (52.88 ± 9.36 s vs. 63.04 ± 20.02 s). The incidence of mucosal injury, sore throat and hoarseness were comparable between two groups. Conclusion RTD maneuver can effectively improve the success rate of first-attempt proper DLT positioning and shorten the time required by bronchial intubation. Trial registration This prospective, double-blind, randomized study has completed the registration of the Chinese Clinical Trial Center at 2/11/2020 with the registration number ChiCTR2000040212. It was conducted from 26/11/2020 to 31/7/2021 in third affiliated hospital of Sun Yat-sen university.

This paper explores the reliability of moral intuitions through the lens of utilitarian ethics, examining both their biological and cultural underpinnings. It argues that while human moral intuitions have a biological basis that aligns with utilitarian principles, these intuitions are significantly influenced and often altered by cultural and societal norms. The first section discusses the biological foundations of moral intuitions, highlighting research on genetic predispositions and neurological factors that support fairness and cooperation as fundamental moral principles. The second section examines how socialization and cultural exposure shape and sometimes distort these intuitions, leading to ethical practices that may diverge from utilitarian standards. Case studies, including the practice of ritual cannibalism, illustrate the conflict between innate moral responses and culturally derived values. The paper concludes that while biological intuitions provide a fundamental ethical framework, the influence of cultural norms necessitates a critical evaluation of moral beliefs to ensure alignment with utilitarian ethics. This underscores the importance of not solely relying on intuitions shaped by cultural contexts but rather assessing them against objective ethical standards. [ABSTRACT FROM AUTHOR]

A growing body of evidence indicates that the immune system plays a central role in sepsis. By analyzing immune genes, we sought to establish a robust gene signature and develop a nomogram that could predict mortality in patients with sepsis. Herein, data were extracted from the Gene Expression Omnibus and Biological Information Database of Sepsis (BIDOS) databases. We enrolled 479 participants with complete survival data using the GSE65682 dataset, and grouped them randomly into training (n = 240) and internal validation (n = 239) sets based on a 1:1 proportion. GSE95233 was set as the external validation dataset (n=51). We validated the expression and prognostic value of the immune genes using the BIDOS database. We established a prognostic immune genes signature (including ADRB2, CTSG, CX3CR1, CXCR6, IL4R, LTB, and TMSB10) via LASSO and Cox regression analyses in the training set. Based on the training and validation sets, the Receiver Operating Characteristic curves and Kaplan-Meier analysis revealed that the immune risk signature has good predictive power in predicting sepsis mortality risk. The external validation cases also showed that mortality rates in the high-risk group were higher than those in the low-risk group. Subsequently, a nomogram integrating the combined immune risk score and other clinical features was developed. Finally, a web-based calculator was built to facilitate a convenient clinical application of the nomogram. In summary, the signature based on the immune gene holds potential as a novel prognostic predictor for sepsis.

The silkworm (Bombyx mori) is not only an excellent model species, but also an important agricultural economic insect. Taking it as the research object, its advantages of low maintenance cost and no biohazard risks are considered. Small open reading frames (smORFs) are an important class of genomic elements that can produce bioactive peptides. However, the smORFs in silkworm had been poorly identified and studied. To further study the smORFs in silkworm, systematic genome-wide identification is essential. Here, we identified and analyzed smORFs in the silkworm using comprehensive methods. Our results showed that at least 738 highly reliable smORFs were found in B. mori and that 34,401 possible smORFs were partially supported. We also identified some differentially expressed and tissue-specific-expressed smORFs, which may be closely related to the characteristics and functions of the tissues. This article provides a basis for subsequent research on smORFs in silkworm, and also hopes to provide a reference point for future research methods for smORFs in other species.

The gravity gradient is a secondary derivative of gravity potential, containing more high-frequency information of Earth's gravity field. Gravity gradient observation data require deducting its prior and intrinsic parts to obtain more variational information. A model generated from a topographic surface database is more appropriate to represent gradiometric effects derived from near-surface mass, as other kinds of data can hardly reach the spatial resolution requirement. The rectangle prism method, namely an analytic integration of Newtonian potential integrals, is a reliable and commonly used approach to modeling gravity gradient, whereas its computing efficiency is extremely low. A modified rectangle prism method and a graphical processing unit (GPU) parallel algorithm were proposed to speed up the modeling process. The modified method avoided massive redundant computations by deforming formulas according to the symmetries of prisms' integral regions, and the proposed algorithm parallelized this method's computing process. The parallel algorithm was compared with a conventional serial algorithm using 1″ elevation data in two topographic areas (rough and moderate terrain). Modeling differences between the two algorithms were less than 0.1 E, which is attributed to precision differences between single-precision and double-precision float numbers. The parallel algorithm showed computational efficiency approximately 200 times higher than the serial algorithm in experiments, demonstrating its effective speeding up in the modeling process. Further analysis indicates that both the modified method and computational parallelism through GPU contributed to the proposed algorithm's performances in experiments.

The bone immune microenvironment can influence the occurrence and progression of bone defects. To date, research on promoting macrophage M2 polarization to improve bone injury repair has been insufficient. In this study, we designed an injectable poly(L-lactic acid) (PLLA) porous microsphere that forms calcium phosphate crystals on its surface by binding to melatonin, followed by bionanomimetic mineralization in vitro. The microsphere is injectable and degradable, and its release of melatonin (MT) and calcium phosphate (CaP) crystals promotes macrophage M2 polarization, reprogramming of macrophages, and enhanced osteogenesis. After LPS stimulation, the proportion of M2-polarized macrophages in the MS@CaP@MT group was 39.2 ± 2.7%, significantly higher than that in other groups (P < 0.05). Further, in the MS@CaP@MT group, rats exhibited bone mineral densities of 129.4 ± 12.8 mg cc-1 at 2 weeks and 171.6 ± 13.6 mg cc-1 at 4 weeks in the defect area, which were significantly higher than those in other groups (P < 0.05). Using an animal model of femoral condylar defects, we demonstrated that MT PLLA porous microspheres loaded with calcium phosphate crystals can improve the immune microenvironment and form a microsphere-centered osteogenesis model. This significantly accelerates bone defect repair and provides a potential strategy for bone defect treatment. [ABSTRACT FROM AUTHOR]

Crossbreeding advantage in hybrids compared with their parents, termed heterosis, has been exhaustively exploited in chicken breeding over the last century. Reports for crossbreeding of elite laying chickens covering rearing and laying period remain infrequent. In this study, resource populations of Rhode Island Red (RIR) and White Leghorn (WL) pure-bred chickens were reciprocally crossed to generate 4 distinct groups that were evaluated for prelaying growth, egg production, and egg quality. Birds monitored for prelaying growth consists of 105 (RIR), 131 (WL), 207 (RIR × WL) and 229 (WL × RIR), and 30 pullets from each group were evaluated. Egg laying records were collected from 102, 89, 147, and 191 hens in the 4 populations, respectively. In addition, expression of 5 candidate genes for egg production in the ovarian follicles was measured by RT-qPCR. Results showed that BW of hatched chicks in the WL line was higher than the other populations. However, the 2 crossbreds grew faster than WL purebred throughout the prelaying period. Low to medium heterosis was observed for BW and body length before the onset of lay. White Leghorn and the hybrids commenced laying earlier than RIR pullets and egg production traits were favorable in the crossbreds compared with purebreds. Heterosis for egg number and clutch size was moderate in WL × RIR but low in RIR × WL hens. Expression of antimullerian hormone gene was high in WL and RIR × WL hybrids, suggesting WL parent-specific enhancing dominant expression. Shell weight was higher in the crossbreds than purebreds at 52 wk of age, but RIR hens laid eggs with higher shell ratio than the other populations (P

ABSTRACT: The objective of this study was to determine the effect of age at photostimulation on sexual maturity and performance of layer breeders. A total of 192 fourteen-wk-old White Leghorn (WL) breeder hens were randomly allocated to 4 treatments of 48 birds each, with 2 replicates per treatment. The birds were photostimulated at 16 (PS16), 18 (PS18), 20 (PS20), and 22 (PS22) wk of age. Four birds per treatment were randomly selected to evaluate sexual organ development at 1 D before photostimulation and 2, 4, and 6 wk after photostimulation. The ovary weight, large yellow follicles number (LYF), oviduct weight, and oviduct length of PS18 increased sharply after photostimulation. Conversely, the increase in PS16 was not observed until 2 wk after photostimulation. There was no difference in age at sexual maturity between treatments (P > 0.05). The PS16 had the longest interval (28 D) from photostimulation to 5% egg production, while PS22 reached 5% egg production 7 D before photostimulation. The PS22 had lower peak production (P = 0.02) and less egg production (P = 0.02) than other treatments. The PS16 had more broken and abnormal eggs (P = 0.01) and lower hatchability (P = 0.04) than other treatments. In conclusion, photostimulation at 16 and 22 wk of age decreases hatchability and egg production, respectively, and photostimulation at 18 wk is appreciated for the WL breeder hens.

Coronavirus disease 2019 (COVID-19) is a serious epidemic, characterized by potential mutation and can bring about poor vaccine efficiency. It is evidenced that patients with malignancies, including prostate cancer (PC), may be highly vulnerable to the SARS-CoV-2 infection. Currently, there are no existing drugs that can cure PC and COVID-19. Luteolin can potentially be employed for COVID-19 treatment and serve as a potent anticancer agent. Our present study was conducted to discover the possible drug target and curative mechanism of luteolin to serve as treatment for PC and COVID-19. The differential gene expression of PC cases was determined via RNA sequencing. The application of network pharmacology and molecular docking aimed to exhibit the drug targets and pharmacological mechanisms of luteolin. In this study, we found the top 20 up- and downregulated gene expressions in PC patients. Enrichment data demonstrated anti-inflammatory effects, where improvement of metabolism and enhancement of immunity were the main functions and mechanism of luteolin in treating PC and COVID-19, characterized by associated signaling pathways. Additional core drug targets, including MPO and FOS genes, were computationally identified accordingly. In conclusion, luteolin may be a promising treatment for PC and COVID-19 based on bioinformatics findings, prior to future clinical validation and application.

NACHT, LRR and PYD domains-containing protein 3 (NLRP3) protein is the core actor involved in inflammasome formation, and plays a pivotal role in the innate immune response. However, whether NLRP3 participates in the regulation of innate immunity in invertebrates is still unknown. In the present study, we characterized a NLRP3 ortholog in Penaeus vannamei (designated PvNLRP3-like) with 2514 bp length of open reading frame (ORF) encoding a putative protein of 837 amino acids. Sequence analysis revealed that PvNLRP3-like contained only NACHT domain and shared closely homology with other invertebrates, but the topological structure of NACHT domain of PvNLRP3-like is similar with that in human NLRP3. PvNLRP3-like was ubiquitously expressed in tissues and induced in hemocytes by Vibrio parahaemolyticus, Streptococcus iniae and White Spot Syndrome Virus (WSSV) challenge, suggesting that PvNLRP3-like participated in the immune responses to pathogens. Furthermore, silencing of PvNLRP3-like followed by V. parahaemolyticus stimulation negatively regulated the transcripts of antimicrobial peptides (AMPs) including Lysozyme (LYZ) 3, Crustin (CRU) 2, Anti-lipopolysaccharide factor (ALF) 2/3 and Penaeidins (PEN) 3/4. This study enriches our current knowledge on shrimp innate immunity, and provides novel perspective to understand the immune regulation role of PvNLRP3-like.

Background: The pathogenesis of inflammatory bowel disease (IBD) is linked to an intricate association of environmental, microbial, and host-related factors. Polysaccharide affects host immunity by regulating the composition and metabolism of gut microbiota is the common mechanism of disease resistance. However, the efficacy and mechanism of Schisandra chinensis polysaccharide (SCP) in the treatment of inflammatory bowel disease have not been studied.Objective: To explore the effect and mechanism of SCP on dextran sodium sulfate (DSS) - induced ulcerative colitis (UC) in mice.Materials/Methods: In this study, we established a mouse model of UC, and used SCP for treatment intervention. The biochemical indexes related to inflammation were determined by ELISA kit, and the therapeutic effect of SCP on UC was clarified. Then, 16S rDNA sequencing was used to study the effect of SCP on the composition and diversity of gut microbiota. At the same time, GC-MS was used to determine the content of short chain fatty acids in intestinal contents. Finally, the relationship among gut microbiota, short chain fatty acids and inflammatory factors was analyzed, and to comprehensively explain the effect and mechanism of SCP on UC.Results: The results showed that SCP could significantly improve the physiological state of UC mice and regulate the level of inflammatory factors to normal levels. Meanwhile, SCP could significantly regulate the imbalance of gut microbiota and increase the content of SCFAs. In addition, the results of the correlation between gut microbiota and SCFAs showed that butyric acid, isobutyric acid and valeric acid had the highest correlation with gut microbiota.Conclusion: In conclusion, this research showed that SCP can inhibit inflammatory bowel disease by regulating the composition and metabolism of gut microbiota, and indicating that SCP may be used as adjuvant therapy for IBD patients.

AimBi-directional relationships between various environmental factors and psychological symptoms can be seen from childhood to adolescence; however, there has been little prospective cohort study, which investigated the relationships simultaneously. In this study, we first distinguished specific psychological symptoms from general psychopathology using bifactor modeling and then tested the relationships between psychological symptoms and environmental factors from childhood to early adolescence using a structural equation model (SEM).MethodsThe analyses were based on Tokyo TEEN Cohort (TTC) data collected between October 2012 and March 2016. We obtained self-reported psychological symptoms and environmental factors from both parents and children (at their ages of 10 and 12). Participants were 3,171 children aged 10 [girls = 1,487 (46.9%), mean age, SD = 10.2, 0.28] and subsequently 12 (N = 3,007, follow-up rate 94.8%, mean age, SD = 12.2, 0.31) from three municipalities in Tokyo area.ResultsThe best-fit symptom models included four unique factors and general psychopathology as the common factor. Combining the good fit bifactor model and the SEM, positive relationships between symptoms and environmental factors at the same waves and some bi-directional relationships were found. Especially, general psychopathology at age 10 was associated with bullying at age 12 and parental depressive symptoms at age 10 with general psychopathology at age 12. However, some negative relationships such as bullying/bullied involvement and later psychological symptoms were also seen.ConclusionBy using the newly introduced methodology, our results were partly consistent with previous literature. Further studies are needed to validate this methodology and accelerate the findings regarding the emergence of psychological symptoms and the impact of environmental factors from childhood to early adolescence.

Background and Purpose: Acute lung injury (ALI) is a serious, life-threatening inflammation of the lungs that still lacks effective treatment. We previously showed that serine protease inhibitor B1 (SerpinB1) protects against ALI induced by orthotopic autologous liver transplantation. However, the role of SerpinB1 in lipopolysaccharide (LPS)-induced ALI and its regulatory mechanisms are not known. Experimental Approach: Wild-type (WT) and SerpinB1 knockout (KO) mice were treated with intratracheal LPS stimulation to induce ALI. Some of the WT and KO mice were injected i.p. with melatonin, a rhythm-related protein Rev-erbα agonist. The circadian rhythm in WT mice was disrupted by exposing mice to 24 h of continuous dark or light conditions after intratracheal LPS. Neutrophils were isolated from alveolar lavage fluid of WT and KO mice, and from human peripheral blood. Neutrophils were treated with LPS and melatonin. Key Results: Disruption of circadian rhythm by either 24-h dark or light conditions exacerbated LPS-induced ALI and decreased expression of Rev-erbα and SerpinB1 protein in lung, whereas melatonin treatment increased SerpinB1 expression and attenuated LPS-induced ALI in WT mice, but not in KO mice. In isolated neutrophils, Rev-erbα was co-localized with SerpinB1 and bound to its promoter to trigger SerpinB1 transcription. Furthermore, LPS stimulation increased formation of neutrophil extracellular traps, which was reversed by melatonin treatment in neutrophils from WT mice, but not from KO mice. Conclusion and Implications: In mice, SerpinB1 is rhythmically regulated by Reverbα, and its down-regulation exacerbates LPS-induced ALI by inducing formation of neutrophil extracellular traps. [ABSTRACT FROM AUTHOR]

Abstract Background TEs pervade mammalian genomes. However, compared with mice, fewer studies have focused on the TE expression patterns in rat, particularly the comparisons across different organs, developmental stages and sexes. In addition, TEs can influence the expression of nearby genes. The temporal and spatial influences of TEs remain unclear yet. Results To evaluate the TEs transcription patterns, we profiled their transcript levels in 11 organs for both sexes across four developmental stages of rat. The results show that most short interspersed elements (SINEs) are commonly expressed in all conditions, which are also the major TE types with commonly expression patterns. In contrast, long terminal repeats (LTRs) are more likely to exhibit specific expression patterns. The expression tendency of TEs and genes are similar in most cases. For example, few specific genes and TEs are in the liver, muscle and heart. However, TEs perform superior over genes on classing organ, which imply their higher organ specificity than genes. By associating the TEs with the closest genes in genome, we find their expression levels are correlated, independent of their distance in some cases. Conclusions TEs sex-dependently associate with nearest genes. A gene would be associated with more than one TE. Our works can help to functionally annotate the genome and further understand the role of TEs in gene regulation.

The c-Jun N-terminal kinase (JNK)/c-Jun cascade-dependent neuronal apoptosis has been identified as a central element for early brain injury (EBI) following subarachnoid hemorrhage (SAH), but the molecular mechanisms underlying this process are still thoroughly undefined to date. In this study, we found that pan-histone deacetylase (HDAC) inhibition by TSA, SAHA, VPA, and M344 led to a remarkable decrease in the phosphorylation of JNK and c-Jun, concomitant with a significant abrogation of apoptosis caused by potassium deprivation in cultured cerebellar granule neurons (CGNs). Further investigation showed that these effects resulted from HDAC inhibition-induced transcriptional suppression of MKK7, a well-known upstream kinase of JNK. Using small interference RNAs (siRNAs) to silence the respective HDAC members, HDAC4 was screened to be required for MKK7 transcription and JNK/c-Jun activation. LMK235, a specific HDAC4 inhibitor, dose-dependently suppressed MKK7 transcription and JNK/c-Jun activity. Functionally, HDAC4 inhibition via knockdown or LMK235 significantly rescued CGN apoptosis induced by potassium deprivation. Moreover, administration of LMK235 remarkably ameliorated the EBI process in SAH rats, associated with an obvious reduction in MKK7 transcription, JNK/c-Jun activity, and neuronal apoptosis. Collectively, the findings provide new insights into the molecular mechanism of neuronal apoptosis regarding HDAC4 in the selective regulation of MKK7 transcription and JNK/c-Jun activity. HDAC4 inhibition could be a potential alternative to prevent MKK7/JNK/c-Jun axis-mediated nervous disorders, including SAH-caused EBI.

Hepatocellular carcinoma (HCC) is currently still a major factor leading to death, lacking of reliable biomarkers. Therefore, deep understanding the pathogenesis for HCC is of great importance. The emergence of circular RNA (circRNA) provides a new way to study the pathogenesis of human disease. Here, we employed the prediction tool to identify circRNAs based on RNA-seq data. Then, to investigate the biological function of the circRNA, the candidate circRNAs were associated with the protein-coding genes (PCGs) by GREAT. We found significant candidate circRNAs expression alterations between normal and tumor samples. Additionally, the PCGs associated with these candidate circRNAs were also found have discriminative expression patterns between normal and tumor samples. The enrichment analysis illustrated that these PCGs were predominantly enriched for liver/cardiovascular-related diseases such as atherosclerosis, myocardial ischemia and coronary heart disease, and participated in various metabolic processes. Together, a further network analysis indicated that these PCGs play important roles in the regulatory and the PPI network. Finally, we built a classification model to distinguish normal and tumor samples by using candidate circRNAs and their associated genes, respectively. Both of them obtained satisfactory results (~ 0.99 of AUC for circRNA and PCG). Our findings suggested that the circRNA could be a critical factor in HCC, providing a useful resource to explore the pathogenesis of HCC.