Exploring the effects of Hippo signaling pathway on rumen epithelial proliferation.

BACKGROUND: The current understanding to the mechanism of rumen development is limited. We hypothesized that the Hippo signaling pathway controlled the proliferation of rumen epithelium (RE) during postnatal development. In the present study, we firstly tested the changes of the Hippo signaling pathway in the RE during an early growing period from d5 to d25, and then we expanded the time range to the whole preweaning period (d10-38) and one week post weaning (d45). An in vitro experiment was also carried out to verify the function of Hippo signaling pathway during RE cell proliferation. RESULTS: In the RE of lambs from d5 to d25, the expression of baculoviral IAP repeat containing (BIRC3/5) was increased, while the expressions of large tumor suppressor kinase 2 (LATS2), TEA domain transcription factor 3 (TEAD3), axin 1 (AXIN1), and MYC proto-oncogene (MYC) were decreased with rumen growth. From d10 to d38, the RE expressions of BIRC3/5 were increased, while the expressions of LATS2 and MYC were decreased, which were similar with the changes in RE from d5 to d25. From d38 to d45, different changes were observed, with the expressions of LATS1/2, MOB kinase activator 1B (MOB1B), and TEAD1 increased, while the expressions of MST1 and BIRC5 decreased. Correlation analysis showed that during the preweaning period, the RE expressions of BIRC3/5 were positively correlated with rumen development variables, while LAST2 was negatively correlated with rumen development variables. The in vitro experiment validated the changes of LATS2 and BIRC3/5 in the proliferating RE cells, which supported their roles in RE proliferation during preweaning period. CONCLUSIONS: Our results suggest that the LATS2-YAP1-BIRC3/5 axis participates in the RE cell proliferation and promotes rumen growth during the preweaning period.

Inhibition of Nogo-B reduces the progression of pancreatic cancer by regulation NF-κB/GLUT1 and SREBP1 pathways.

Pancreatic cancer (PC) is a lethal disease and associated with metabolism dysregulation. Nogo-B is related to multiple metabolic related diseases and types of cancers. However, the role of Nogo-B in PC remains unknown. In vitro, we showed that cell viability and migration was largely reduced in Nogo-B knockout or knockdown cells, while enhanced by Nogo-B overexpression. Consistently, orthotopic tumor and metastasis was reduced in global Nogo knockout mice. Furthermore, we indicated that glucose enhanced cell proliferation was associated to the elevation expression of Nogo-B and nuclear factor κB (NF-κB). While, NF-κB, glucose transporter type 1 (GLUT1) and sterol regulatory element-binding protein 1 (SREBP1) expression was reduced in Nogo-B deficiency cells. In addition, we showed that GLUT1 and SREBP1 was downstream target of NF-κB. Therefore, we demonstrated that Nogo deficiency inhibited PC progression is regulated by the NF-κB/GLUT1 and SREBP1 pathways, and suggested that Nogo-B may be a target for PC therapy.

Multiparticle collision dynamics simulations of hydrodynamic interactions in colloidal suspensions: How well does the discrete particle approach do at short range?

The multiparticle collision dynamics (MPCD) simulation method is an attractive technique for studying the effects of hydrodynamic interactions in colloidal suspensions because of its flexibility, computational efficiency, and ease of implementation. Here, we analyze an extension of the basic MPCD method in which colloidal particles are discretized with a surface mesh of sensor nodes/particles that interact with solvent particles (MPCD + Discrete Particle or MPCD + DP). We use several situations that have been described analytically to probe the impact of colloidal particle mesh resolution on the ability of the MPCD + DP method to resolve short-ranged hydrodynamic interactions, which are important in crowded suspensions and especially in self-assembling systems that create high volume fraction phases. Specifically, we consider (A) hard-sphere diffusion near a wall, (B) two-particle diffusion, (C) hard-sphere diffusion in crowded suspensions, and (D) the dynamics of aggregation in an attractive colloidal suspension. We show that in each case, the density of sensor nodes plays a significant role in the accuracy of the simulation and that a surprisingly high number of surface nodes are needed to fully capture hydrodynamic interactions.

Metabolic Activation and Cytotoxicity of Gramine Mediated by CYP3A in Rats.

Gramine (GRM), which occurs in Gramineae plants, has been developed to be a biological insecticide. Exposure to GRM was reported to induce elevations of serum ALT and AST in rats, but the mechanisms of the observed hepatotoxicity have not been elucidated. The present study aimed to identify reactive metabolites that potentially participate in the toxicity. In rat liver microsomal incubations fortified with glutathione or N-acetylcysteine, one oxidative metabolite (M1), one glutathione conjugate (M2), and one N-acetylcysteine conjugate (M3) were detected after exposure to GRM. The corresponding conjugates were detected in the bile and urine of rats after GRM administration. CYP3A was the main enzyme mediating the metabolic activation of GRM. The detected GSH and NAC conjugates suggest that GRM was metabolized to a quinone imine intermediate. Both GRM and M1 showed significant toxicity to rat primary hepatocytes.

Multi-omics integrated analyses indicated that non-polysaccharides of Sijunzi decoction ameliorated spleen deficiency syndrome via regulating microbiota-gut-metabolites axis and exerted synergistic compatibility.

ETHNOPHARMACOLOGICAL RELEVANCE: As a classical traditional Chinese medicine formula to invigorating spleen and replenishing qi, Sijunzi decoction (SJZD) is composed of four herbs, which is applied to cure spleen deficiency syndrome (SDS) clinically. The non-polysaccharides (NPSs) of SJZD (SJZD_NPS) are important pharmacodynamic material basis. However, the amelioration mechanism of SJZD_NPS on SDS has not been fully elaborated. Additionally, the contribution of herbs compatibility to efficacy of this formula remains unclear. AIM OF THE STUDY: The aim was to explore the underlying mechanisms of SJZD_NPS on improving SDS, and uncover the scientific connotation in SJZD compatibility. MATERIALS AND METHODS: A strategy integrating incomplete formulae (called "Chai-fang" in Chinese) comparison, pharmacodynamics, gut microbiome, and metabolome was employed to reveal the role of each herb to SJZD compatibility against SDS. Additionally, the underlying mechanism harbored by SJZD_NPS was further explored through targeted metabolomics, network pharmacology, molecular docking, pseudo-sterile model, and metagenomics. RESULTS: SJZD_NPS significantly alleviated diarrhea, disordered secretion of gastrointestinal hormones and neurotransmitters, damage of ileal morphology and intestinal barrier in SDS rats, which was superior to the NPSs of Chai-fang. 16S rRNA gene sequencing and metabolomics analyses revealed that SJZD_NPS effectively restored the disturbed gut microbiota community and abnormal metabolism caused by SDS, showing the most evident recovery. Moreover, SJZD_NPS recalled the levels of partial amino acids, short chain fatty acids and bile acids, which possessed strong binding affinity towards potential targets. The depletion of gut microbiota confirmed that the SDS-amelioration efficacy of SJZD_NPS is dependent on the intact gut microbiome, with the relative abundance of potential probiotics such as Lactobacillus_johnsonii and Lactobacillus_taiwanensis been enriched. CONCLUSION: NPSs in SJZD can improve SDS-induced gastrointestinal-nervous system dysfunction through regulating microbiota-gut-metabolites axis, with four herbs exerting synergistic effects, which indicated the compatibility rationality of SJZD.

Classical and novel properties of Holliday junction resolvase SynRuvC from Synechocystis sp. PCC6803.

Cyanobacteria, which have a photoautotrophic lifestyle, are threatened by ultraviolet solar rays and the reactive oxygen species generated during photosynthesis. They can adapt to environmental conditions primarily because of their DNA damage response and repair mechanisms, notably an efficient homologous recombination repair system. However, research on double-strand break (DSB) repair pathways, including the Holliday junction (HJ) resolution process, in Synechocystis sp. PCC6803 is limited. Here, we report that SynRuvC from cyanobacteria Synechocystis sp. PCC6803 has classical HJ resolution activity. We investigated the structural specificity, sequence preference, and biochemical properties of SynRuvC. SynRuvC strongly preferred Mn2+ as a cofactor, and its cleavage site predominantly resides within the 5'-TG↓(G/A)-3' sequence. Interestingly, novel flap endonuclease and replication fork intermediate cleavage activities of SynRuvC were also determined, which distinguish it from other reported RuvCs. To explore the effect of SynRuvC on cell viability, we constructed a knockdown mutant and an overexpression strain of Synechocystis sp. PCC6803 (synruvCKD and synruvCOE) and assessed their survival under a variety of conditions. Knockdown of synruvC increased the sensitivity of cells to MMS, HU, and H2O2. The findings suggest that a novel RuvC family HJ resolvase SynRuvC is important in a variety of DNA repair processes and stress resistance in Synechocystis sp. PCC6803.

Low-Dose Colchicine Ameliorates Doxorubicin Cardiotoxicity Via Promoting Autolysosome Degradation.

BACKGROUND: The only clinically approved drug that reduces doxorubicin cardiotoxicity is dexrazoxane, but its application is limited due to the risk of secondary malignancies. So, exploring alternative effective molecules to attenuate its cardiotoxicity is crucial. Colchicine is a safe and well-tolerated drug that helps reduce the production of reactive oxygen species. High doses of colchicine have been reported to block the fusion of autophagosomes and lysosomes in cancer cells. However, the impact of colchicine on the autophagy activity within cardiomyocytes remains inadequately elucidated. Recent studies have highlighted the beneficial effects of colchicine on patients with pericarditis, postprocedural atrial fibrillation, and coronary artery disease. It remains ambiguous how colchicine regulates autophagic flux in doxorubicin-induced heart failure. METHODS AND RESULTS: Doxorubicin was administered to establish models of heart failure both in vivo and in vitro. Prior studies have reported that doxorubicin impeded the breakdown of autophagic vacuoles, resulting in damaged mitochondria and the accumulation of reactive oxygen species. Following the administration of a low dose of colchicine (0.1 mg/kg, daily), significant improvements were observed in heart function (left ventricular ejection fraction: doxorubicin group versus treatment group=43.75%±3.614% versus 57.07%±2.968%, P=0.0373). In terms of mechanism, a low dose of colchicine facilitated the degradation of autolysosomes, thereby mitigating doxorubicin-induced cardiotoxicity. CONCLUSIONS: Our research has shown that a low dose of colchicine is pivotal in restoring the autophagy activity, thereby attenuating the cardiotoxicity induced by doxorubicin. Consequently, colchicine emerges as a promising therapeutic candidate to improve doxorubicin cardiotoxicity.

Identification of a risk score model based on tertiary lymphoid structure-related genes for predicting immunotherapy efficacy in non-small cell lung cancer.

BACKGROUND: Tertiary lymphoid structures (TLSs) affect the prognosis and efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC), but the underlying mechanisms are not well understood. METHODS: TLSs were identified and categorized online from the Cancer Digital Slide Archive (CDSA). Overall survival (OS) and disease-free survival (DFS) were analyzed. GSE111414 and GSE136961 datasets were downloaded from the GEO database. GSVA, GO and KEGG were used to explore the signaling pathways. Immune cell infiltration was analyzed by xCell, ssGSEA and MCP-counter. The analysis of WGCNA, Lasso and multivariate cox regression were conducted to develop a gene risk score model based on the SU2C-MARK cohort. RESULTS: TLS-positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029). Both the TLS-positive and TLS-mature groups exhibited genes enrichment in immune activation pathways. The TLS-mature group showed more activated dendritic cell infiltration than the TLS-immature group. We screened TLS-related genes using WGCNA. Lasso and multivariate cox regression analysis were used to construct a five-genes (RGS8, RUF4, HLA-DQB2, THEMIS, and TRBV12-5) risk score model, the progression free survival (PFS) and OS of patients in the low-risk group were markedly superior to those in the high-risk group (p < 0.0001; p = 0.0015, respectively). Calibration and ROC curves indicated that the combined model with gene risk score and clinical features could predict the PFS of patients who have received immunotherapy more accurately than a single clinical factor. CONCLUSIONS: Our data suggested a pivotal role of TLSs formation in survival outcome and immunotherapy response of NSCLC patients. Tumors with mature TLS formation showed more activated immune microenvironment. In addition, the model constructed by TLS-related genes could predict the response to immunotherapy and is meaningful for clinical decision-making.

Comparative Analysis of the Complete Mitochondrial Genomes of Three Sisoridae (Osteichthyes, Siluriformes) and the Phylogenetic Relationships of Sisoridae.

The family Sisoridae is one of the largest and most diverse Asiatic catfish families, with most species occurring in the water systems of the Qinhai-Tibetan Plateau and East Himalayas. At present, the phylogenetic relationship of the Sisoridae is relatively chaotic. In this study, the mitochondrial genomes (mitogenomes) of three species Creteuchiloglanis kamengensis, Glaridoglanis andersonii, and Exostoma sp. were systematically investigated, the phylogenetic relationships of the family were reconstructed and to determine the phylogenetic position of Exostoma sp. within Sisoridae. The lengths of the mitogenomes' sequences of C. kamengensis, G. andersonii, and Exostoma sp. were 16,589 bp, 16,531 bp, and 16,529 bp, respectively. They all contained one identical control region (D-loop), two ribosomal RNAs (rRNAs), 13 protein-coding genes (PCGs) and 22 transfer RNA (tRNA) genes. We applied two approaches, Bayesian Inference (BI) and Maximum Likelihood (ML), to construct phylogenetic trees. Our findings revealed that the topological structure of both ML and BI trees exhibited significant congruence. Specifically, the phylogenetic tree strongly supports the monophyly of Sisorinae and Glyptosternoids and provides new molecular biological data to support the reconstruction of phylogenetic relationships with Sisoridae. This study is of great scientific value for phylogenetic and genetic variation studies of the Sisoridae.

[Buzhong Yiqi Decoction ameliorates spleen deficiency syndrome by regulating gut microbiota].

This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1ß, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1ß, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500＿29＿marine＿group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1ß level had a significantly positive correlation with Acinetobacter and CL500＿29＿marine＿group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.

Effective Nonstoichiometric Strategy Combined Post-annealing Process for Boosting Thermoelectric Properties in n-Type PbTe.

The intrinsic low electrical properties have hindered the enhancement of thermoelectric performance for n-type PbTe over a long period of time, primarily due to the generation of intrinsic Pb vacancies and other defects. In this work, PbTe samples with nonstoichiometric excess Pb atoms were successfully prepared by a melting reaction followed by spark plasma sintering. First, the introduction of precisely controlled excess Pb atoms has effectively eliminated the typical p-n transition phenomenon in PbTe systems by suppressing the generation of Pb vacancies. Further, the vacuum annealing process employed in nonstoichiometric samples increases the carrier mobility significantly because of the improved crystallinity and the lowered holes. Thus, the Hall mobility was optimized from 754.3 to 1215.9 cm2 V-1 s-1, while the power factor was ultimately elevated from 3087.8 to 4565.7 µW m-1 K-2 for the Pb1.03Te sample at 323 K. Benefited from the enhanced electrical transport properties near room temperature, an average zT ∼ 1.03 ranging from 323 to 723 K was achieved, demonstrating an outstanding performance in n-type nondoped PbTe. This work provides guidance for optimizing the thermoelectric performance of n-type PbTe and relevant telluride by reducing vacancies and other defects.

Newly identified peptide Nigrocin-OA27 inhibits UVB induced melanin production via the MITF/TYR pathway.

Melasma is a common skin disease induced by an increase in the content of melanin in the skin, which also causes serious physical and mental harm to patients. In this research, a novel peptide (Nigrocin-OA27) from Odorrana andersonii is shown to exert a whitening effect on C57 mice pigmentation model. The peptide also demonstrated non-toxic and antioxidant capacity, and can significantly reduce melanin content in B16 cells. Topical application effectively delivered Nigrocin-OA27 to skin's epidermal and dermal layers and exhibited significant preventive and whitening effects on the UVB-induced ear pigmentation model in C57 mice. The whitening mechanism of Nigrocin-OA27 may be related to reduced levels of the microphthalmia-associated transcription factor and the key enzyme for melanogenesis-tyrosinase (TYR). Nigrocin-OA27 also inhibited the catalytic activity by adhering to the active core of TYR, thereby reducing melanin formation and deposition. In conclusion, Nigrocin-OA27 may be a potentially effective external agent to treat melasma by inhibiting aberrant skin melanin synthesis.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Knowledge, attitude, practice, needs, and implementation status of intensive care unit staff toward continuous renal replacement therapy: a survey of 66 hospitals in central and South China.

BACKGROUND: Continuous renal replacement therapy (CRRT) is a commonly utilized form of renal replacement therapy (RRT) in the intensive care unit (ICU). A specialized CRRT team (SCT, composed of physicians and nurses) engage playing pivotal roles in administering CRRT, but there is paucity of evidence-based research on joint training and management strategies. This study armed to evaluate the knowledge, attitude, and practice (KAP) of ICU staff toward CRRT, and to identify education pathways, needs, and the current status of CRRT implementation. METHODS: This study was performed from February 6 to March 20, 2023. A self-made structured questionnaire was used for data collection. Descriptive statistics, T-tests, Analysis of variance (ANOVA), multiple linear regression, and Pearson correlation coefficient tests (α = 0.05) were employed. RESULTS: A total of 405 ICU staff from 66 hospitals in Central and South China participated in this study, yielding 395 valid questionnaires. The mean knowledge score was 51.46 ± 5.96 (61.8% scored highly). The mean attitude score was 58.71 ± 2.19 (73.9% scored highly). The mean practice score was 18.15 ± 0.98 (85.1% scored highly). Multiple linear regression analysis indicated that gender, age, years of CRRT practice, ICU category, and CRRT specialist panel membership independently affected the knowledge score; Educational level, years of CRRT practice, and CRRT specialist panel membership independently affected the attitude score; Education level and teaching hospital employment independently affected the practice score. The most effective method for ICU staff to undergo training and daily work experience is within the department. CONCLUSION: ICU staff exhibit good knowledge, a positive attitude and appropriately practiced CRRT. Extended CRRT practice time in CRRT, further training in a general ICU or teaching hospital, joining a CRRT specialist panel, and upgraded education can improve CRRT professional level. Considering the convenience of training programs will enhance ICU staff participation. Training should focus on basic CRRT principles, liquid management, and alarm handling.

Sublethal effect and detoxifying metabolism of metaflumizone and indoxacarb on the fall armyworm, Spodoptera frugiperda.

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera, Noctuidae), is a highly polyphagous invasive pest that damages various crops. Pesticide control is the most common and effective strategy to control FAW. In this study, we evaluated the toxicity of metaflumizone and indoxacarb against third-instar FAW larvae using the insecticide-incorporated artificial diet method under laboratory conditions. Both metaflumizone and indoxacarb exhibited substantial toxicity against FAW, with LC50 values of 2.43 and 14.66 mg/L at 72 h, respectively. The sublethal effects of metaflumizone and indoxacarb on parental and F1 generation FAW were investigated by exposing third-instar larvae to LC10 and LC30 concentrations of these insecticides. Sublethal exposure to these two insecticides significantly shortened adult longevity, extended pupal developmental times and led to reduced pupal weight, pupation rates, and adult fecundity in the treated parental generation and F1 generation at LC10 or LC30 concentrations, in comparison to the control group. The larval developmental times were shortened in the parental generation but prolonged in the F1 generation, after being treated with sublethal concentrations of metaflumizone. Furthermore, larvae exposed to LC10 or LC30 concentrations of indoxacarb exhibited elevated activity levels of cytochrome P450 monooxygenase and glutathione S-transferase, which coincides with the observed synergistic effect of piperonyl butoxide and diethyl maleate. In conclusion, the high toxicity and negative impact of metaflumizone and indoxacarb on FAW provided significant implications for the rational utilization of insecticides against this pest.

Yak IGFBP3 promotes hepatocyte proliferation through PI3K-Akt signaling pathway.

IGFBP3 (Insulin-like growth factor binding protein 3) constitutes a crucial constituent of the insulin-like growth factor (IGF), which are intimately associated with the organism's growth and development processes. Despite its significance, the precise function of IGFBP3 in yak liver development remains largely unexplored. In the present study, we systematically examined the expression profile of IGFBP3 in the liver tissues of yaks across various growth stages, elucidated its influence on the activity of yak hepatocytes, and probed its effects on murine liver development. A comparative analysis revealed that the expression of IGFBP3 was significantly higher in the liver tissue of 5-year-old yaks compared to their 15-month-old and 1-day-old counterparts (P < 0.01). To further validate its biological function, pET-28a-BgIGFBP3 prokaryotic expression vector was constructed. Upon exposing yak hepatocytes to varying concentrations of Bos grunniens (Bg) IGFBP3 protein, we observed augmented cellular activities and elevated colony formation rates. Moreover, our investigation revealed the upregulation of key genes within the PI3K-Akt signaling pathway, including ERBB2, IRS1, PIK3R1, AKT1, RAF1, MAP2K2, and MAPK3, in both yak hepatocyte cultures and murine models. These findings collectively indicate that BgIGFBP3 promotes the proliferation of yak hepatocytes and enhances murine liver development by modulating the PI3K-Akt signaling pathway. The functional relevance of BgIGFBP3 was substantiated through in vivo and in vitro experiments, thereby underscoring its potential as a regulatory factor in liver development processes.

Enhanced treatment of acute organophosphorus pesticide poisoning using activated charcoal-embedded sodium alginate-polyvinyl alcohol hydrogel.

BACKGROUND: The adsorption of activated charcoal is currently a major clinical treatment for acute organophosphorus pesticide poisoning (AOPP). However, the adsorption duration and efficiency of this method is unstable. OBJECTIVE: In this study, a hydrogel embedding activated charcoal was prepared and its alleviating effects on AOPP were investigated. METHODS: A composite hydrogel using sodium alginate and polyvinyl alcohol (SA-PVA) hydrogel was prepared in this study. The structural properties of the SA-PVA hydrogel were characterized via multiple analysis including FTIR, TGA, XRD, SEM, tensile strength and expansion rate. Based on these, activated charcoal (AC) was embedded within the SA-PVA hydrogel (SA-PVA-AC) and it was used for the treatment of AOPP. RESULTS: Structural characterization indicated SA-PVA hydrogel possesses excellent mechanical properties and biocompatibility. The in vivo study demonstrated that SA-PVA-AC significantly alleviated the inflammation and oxidative damage in the liver, as evidenced by reduced levels of IL-6, TNF-α, and, IL-1ß, SOD, and MDA. Furthermore, SA-PVA-AC treatment effectively re-regulated the activities of serum AST and ALT, exhibiting an improved effect on liver function. CONCLUSION: The findings suggest that activated charcoal embedded within SA-PVA hydrogel has significant potential as a therapeutic agent in treating AOPP, and offering a novel approach to managing pesticide-induced toxicity.

Robotic-assisted laparoscopic versus abdominal and laparoscopic myomectomy: A systematic review and meta-analysis.

BACKGROUND: Myomectomy is the preferred treatment for women with uterine fibroids and fertility requirements. There are three modalities are used in clinical practice for myomectomy: abdominal myomectomy (AM), laparoscopic myomectomy (LM), and robot-assisted laparoscopic myomectomy (RLM). OBJECTIVES: To compare the perioperative and postoperative outcomes of RLM, AM, and LM. SEARCH STRATEGY: We searched PubMed, Web of Science, Embase, and Clinical Trials for relevant literature published between January 2000 and January 2023. SELECTION CRITERIA: We included all studies reporting peri- and postoperative outcomes of myomectomy in patients with uterine myomas. Surgical treatments were classified as RLM, LM, or AM. DATA COLLECTION AND ANALYSIS: Two or more authors selected studies independently, assessed risk of bias, and extracted data. We derived mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CIs) for each outcome, subgrouping trials by the patient characteristics and myoma characteristics. We used the I2 statistic to quantify heterogeneity and the random-effects model for meta-analysis when appropriate. We used the funnel plot to assess the publication bias. MAIN RESULTS: A total of 32 studies with 6357 patients were included, of which 1982 women had undergone RLM. The operating time was significantly longer (MD = 43.58, 95% confidence interval [CI]: 25.22-61.93, P < 0.001), and the incidence of cesarean section after myomectomy was significantly lower (OR = 0.27, 95% CI: 0.10-0.78, P = 0.02) in RLM than in LM. Compared with AM, the operation time, blood loss, blood transfusion rate, complication rate, total cost, length of hospital stay, and pregnancy rate of patients with RLM were significantly different. CONCLUSIONS: The safety and effectiveness of RLM are superior to those of AM but inferior to those of LM.

Atorvastatin causes developmental and behavioral toxicity in yellowstripe goby (Mugilogobius chulae) embryos/larvae via disrupting lipid metabolism and autophagy processes.

Atorvastatin (ATV) is one of the most commonly prescribed lipid-lowering drugs detected frequently in the environment due to its high use and low degradation rate. However, the toxic effects of residual ATV in the aquatic environment on non-target organisms and its toxic mechanisms are still largely unknown. In the present study, embryos of a native estuarine benthic fish, Mugilogobius chulae, were employed to investigate the developmental and behavioral toxic effects of ATV including environmentally relevant concentrations. The aim of this study was to provide a scientific basis for ecological risk assessment of ATV in the aquatic environment by investigating the changes of biological endpoints at multiple levels in M. chulae embryos/larvae. The results showed that ATV had significantly lethal and teratogenic effects on M. chulae embryos/larvae and caused abnormal changes in developmental parameters including hatch rate, body length, heart rate, and spontaneous movement. ATV exposure caused oxidative stress in M. chulae embryos/larvae subsequently inhibited autophagy and activated apoptosis, leading to abnormal developmental processes and behavioral changes in M. chulae embryos/larvae. The disruptions of lipid metabolism, autophagy, and apoptosis in M. chulae embryos/larvae caused by ATV exposure may pose a potential ecological risk at the population level.

Electrochemical Oxidative (4 + 2) Cyclization of Anilines and o-Phenylenediamines for the Synthesis of Phenazines.

Phenazines, crucial constituents of nitrogen-containing heterocycles, widely exist in functional compounds. Herein, we report an anodic oxidative (4 + 2) cyclization between anilines and o-phenylenediamines for the uniform construction of phenazines in a simple undivided cell. Dual C-H amination followed by oxidation represents an outstanding step and atom efficiency. A sequence of phenazines is produced with excellent functional group tolerance at room temperature.