Evaluation of Clostridium autoethanogenum protein as a new protein source for broiler chickens in replacement of soybean meal.

Objective: The object of this study was to investigate the effect of replacing soybean meal with Clostridium autoethanogenum protein (CAP) in broiler diets on growth performance, blood indicators, antioxidant capacity, and immune function. Methods: A total of 180 Arbor Acres broilers were randomly divided into three treatments, each treatment with six replicates and 10 broilers per replicate for a 42-day feeding trial. The control group (CON) was fed corn-soybean meal based diet. The CAP-1 and CAP-2 groups were considered to use CAP to replace 25% or 50% of soybean meal in the diet, respectively. The average daily gain and average daily feed intake of broilers at 1-21 d, 22-42 d, and 1-42 d were measured, and the feed conversion ratio was calculated. At the 42nd day of age, two broilers with similar weights and fasted for 12h were selected in each replicate for blood collection from the brachial wing vein. The blood routine indicators, serum biochemical indicators, serum antioxidant capacity, and immunoglobulin content of broiler chickens were measured. Results: Replacement of soybean meal with 25% (CAP-1) and 50% (CAP-2) CAP significantly increased the average daily gain of 22-42 d and 1-42 d and decreased the average daily feed intake and feed conversion rate (p<0.05). The CAP-1 group, and CAP-2 group significantly increased hemoglobulin in the blood of broilers, while the CAP-2 group increased hematocrit content (p<0.05). Compared with the control group, the contents of superoxide dismutase and immunoglobulin A in serum of the CAP-2 group were significantly increased, while the contents of malondialdehyde in CAP group were significantly decreased (p<0.05). Conclusion: Replacing soybean meal with CAP led to significant improvements in the growth performance, antioxidant capacity, and immunoglobulin content of broilers.

Ultrahigh and kinetic-favorable adsorption for recycling urea using corncob-derived porous biochar.

Insufficient attention has been given to the recycling of excess urea despite its potential detrimental effects on soil nutrient equilibrium, geological structure, and crop health. In this study, corncob-derived porous biochar (CPB), which is rich in surface functional groups, was prepared from biomass corncob in two steps as an adsorbent to remove urea from wastewater. Compared with the typical carbonization and activation processes, this process resulted in a higher yield of CPB and an ultrahigh adsorption capacity for urea. Response surface analysis was utilized to determine the optimal carbonization conditions, which were found to be 500 °C for 6 h with a heating rate of 15 °C/min. The exceptional adsorption capability of CPB can be ascribed to its porous structure and significant presence of oxygen-containing functional groups, which facilitate a synergistic interaction of physisorption and chemisorption. This adsorption phenomenon aligns with the Harkins-Jura isotherm model and adheres to pseudo-second order kinetics. CPB demonstrates potential as an adsorbent for the elimination of urea from wastewater in an economical and effective fashion.

Construction of ceRNA network mediated by circRNAs screening from microarray and identification of novel biomarkers for myasthenia gravis.

BACKGROUND: Recent studies have revealed that circRNA can serve as ceRNA to participate in multiple autoimmune diseases. Our study aims to explore the key circRNA as ceRNA and biomarker for MG. METHODS: We used circRNA microarray to explore differentially expressed circRNAs (DECs) from MG and compare with control. Then, we predicted the target miRNA associated with DECs and screened miRNAs by the algorithm of random walk with restart (RWR). Next, we constructed the circRNA-miRNA-mRNA ceRNA regulated network (CMMC) to identify the hub objects. Following, we detected the expression of hub-circRNAs by RT-PCR. We verify has_circ_0004183 (circFRMD4) sponging miR-145-5p regulate cells proliferation using luciferase assay and CCK-8. RESULTS: We found that the expression level of circFRMD4 and has_circ_0035381 (circPIGB) were upregulated and has_circ_0089153(circ NUP214) had the lowest expression level in MG. Finally, we proved circFRMD4 sponging miR-145-5p regulate Jurkat cells proliferation. CircFRMD4 take part in the genesis and development of MG via circFRMD4/miR145-5p axis. CONCLUSIONS: We found that circFRMD4, circPIGB and circNUP214 can be considered as valuable potential novel biomarkers for AchR + MG. CircFRMD4 participate in the development of AchR + MG via targeting binding with miR-145-5p.

Sensing of mitochondrial DNA by ZBP1 promotes RIPK3-mediated necroptosis and ferroptosis in response to diquat poisoning.

Diquat (DQ) poisoning is a severe medical condition associated with life-threatening implications and multiorgan dysfunction. Despite its clinical significance, the precise underlying mechanism remains inadequately understood. This study elucidates that DQ induces instability in the mitochondrial genome of endothelial cells, resulting in the accumulation of Z-form DNA. This process activates Z-DNA binding protein 1 (ZBP1), which then interacts with receptor-interacting protein kinase 3 (RIPK3), ultimately leading to RIPK3-dependent necroptotic and ferroptotic signaling cascades. Specific deletion of either Zbp1 or Ripk3 in endothelial cells simultaneously inhibits both necroptosis and ferroptosis. This dual inhibition significantly reduces organ damage and lowers mortality rate. Notably, our investigation reveals that RIPK3 has a dual role. It not only phosphorylates MLKL to induce necroptosis but also phosphorylates FSP1 to inhibit its enzymatic activity, promoting ferroptosis. The study further shows that deletion of mixed lineage kinase domain-like (Mlkl) and the augmentation of ferroptosis suppressor protein 1 (FSP1)-dependent non-canonical vitamin K cycling can provide partial protection against DQ-induced organ damage. Combining Mlkl deletion with vitamin K treatment demonstrates a heightened efficacy in ameliorating multiorgan damage and lethality induced by DQ. Taken together, this study identifies ZBP1 as a crucial sensor for DQ-induced mitochondrial Z-form DNA, initiating RIPK3-dependent necroptosis and ferroptosis. These findings suggest that targeting the ZBP1/RIPK3-dependent necroptotic and ferroptotic pathways could be a promising approach for drug interventions aimed at mitigating the adverse consequences of DQ poisoning.

LncRNA lncMGR regulates skeletal muscle development and regeneration by recruiting CDK9 and sponging miRNAs.

Long non-coding RNAs (lncRNAs) play an essential role in vertebrate myogenesis and muscle diseases. However, the dynamic expression patterns, biological functions, and mechanisms of lncRNAs in skeletal muscle development and regeneration remain largely unknown. In this study, a novel lncRNA (named lncMGR) was differentially expressed during breast muscle development in fast- and slow-growing chickens. Functionally, lncMGR promoted myoblast differentiation, inhibited myoblast proliferation in vitro, and promoted myofiber hypertrophy and injury repair in vivo. Mechanistically, lncMGR increased the mRNA and protein expression of skeletal muscle myosin heavy chain 1 A (MYH1A) via both transcriptional and post-transcriptional regulation. Nuclear lncMGR recruited cyclin-dependent kinase 9 (CDK9) to the core transcriptional activation region of the MYH1A gene to activate MYH1A transcription. Cytoplasmic lncMGR served as a competitive endogenous RNA (ceRNA) to competitively absorb miR-2131-5p away from MYH1A and subsequently protected the MYH1A from miR-2131-5p-mediated degradation. Besides miR-2131-5p, cytoplasmic lncMGR could also sponge miR-143-3p to reconcile the antagonist between the miR-2131-5p/MYH1A-mediated inhibition effects and miR-143-3p-mediated promotion effects on myoblast proliferation, thereby inhibiting myoblast proliferation. Collectively, lncMGR could recruit CDK9 and sponge multiple miRNAs to regulate skeletal muscle development and regeneration, and could be a therapeutic target for muscle diseases.

Molecular characteristics and biofilm formation capacity of nontypeable Haemophilus influenza strains isolated from lower respiratory tract in children.

With the widespread introduction of the Hib conjugate vaccine, Nontypeable Haemophilus influenzae (NTHi) has emerged as the predominant strain globally. NTHi presents a significant challenge as a causative agent of chronic clinical infections due to its high rates of drug resistance and biofilm formation. While current research on NTHi biofilms in children has primarily focused on upper respiratory diseases, investigations into lower respiratory sources remain limited. In this study, we collected 54 clinical strains of lower respiratory tract origin from children. Molecular information and drug resistance features were obtained through whole gene sequencing and the disk diffusion method, respectively. Additionally, an in vitro biofilm model was established. All clinical strains were identified as NTHi and demonstrated the ability to form biofilms in vitro. Based on scanning electron microscopy and crystal violet staining, the strains were categorized into weak and strong biofilm-forming groups. We explored the correlation between biofilm formation ability and drug resistance patterns, as well as clinical characteristics. Stronger biofilm formation was associated with a longer cough duration and a higher proportion of abnormal lung imaging findings. Frequent intake of ß-lactam antibiotics might be associated with strong biofilm formation. While a complementary relationship between biofilm-forming capacity and drug resistance may exist, further comprehensive studies are warranted. This study confirms the in vitro biofilm formation of clinical NTHi strains and establishes correlations with clinical characteristics, offering valuable insights for combating NTHi infections.

The improved aquila optimization approach for cost-effective design of hybrid renewable energy systems.

The growing demand for renewable energy systems is driven by climate change concerns, government support, technological advancements, economic viability, and energy security. These factors combine to create a strong momentum towards a clean and sustainable energy future. Governments, governments, and individuals are increasingly aware of the environmental impacts of traditional energy sources and adopting renewable energy solutions. Hybrid Renewable Energy Systems (HRES) are developed as an effective way of meeting the energy demands in remote locations. The complexity of the system components and the fluctuation of renewable energy sources make it difficult to design an economical and effective HRES. In this study, the Improved Aquila Optimization (IAO) approach has been suggested as a powerful tool to optimize the HRES design. The study addresses the implementation of the IAO approach in the design of HRES and emphasizes its advantages over other optimization techniques. Through extensive simulations and analyses, our findings demonstrate the superior performance of the IAO algorithm in improving the efficiency and cost-effectiveness of HRES. The optimization process using IAO resulted in a significant reduction in overall system costs, achieving an estimated Net Present Cost (NPC) of $201,973. It translates to a cost reduction of 25% compared to conventional optimization techniques. Furthermore, our analysis reveals that the IAO approach enhances the utilization of renewable energy sources, leading to a 15% increase in overall energy generation efficiency. These results highlight the effectiveness of the IAO approach in addressing the challenges associated with designing HRES. By significantly reducing costs and improving efficiency, it facilitates the adoption of sustainable energy systems in remote areas. The outcomes of this study emphasize the importance of utilizing advanced optimization techniques, such as IAO, to ensure the economic viability and environmental sustainability of HRES.

Functional overlap between the mammalian Sar1a and Sar1b paralogs in vivo.

Proteins carrying a signal peptide and/or a transmembrane domain enter the intracellular secretory pathway at the endoplasmic reticulum (ER) and are transported to the Golgi apparatus via COPII vesicles or tubules. SAR1 initiates COPII coat assembly by recruiting other coat proteins to the ER membrane. Mammalian genomes encode two SAR1 paralogs, SAR1A and SAR1B. While these paralogs exhibit ~90% amino acid sequence identity, it is unknown whether they perform distinct or overlapping functions in vivo. We now report that genetic inactivation of Sar1a in mice results in lethality during mid-embryogenesis. We also confirm previous reports that complete deficiency of murine Sar1b results in perinatal lethality. In contrast, we demonstrate that deletion of Sar1b restricted to hepatocytes is compatible with survival, though resulting in hypocholesterolemia that can be rescued by adenovirus-mediated overexpression of either SAR1A or SAR1B. To further examine the in vivo function of these 2 paralogs, we genetically engineered mice with the Sar1a coding sequence replacing that of Sar1b at the endogenous Sar1b locus. Mice homozygous for this allele survive to adulthood and are phenotypically normal, demonstrating complete or near-complete overlap in function between the two SAR1 protein paralogs in mice. These data also suggest upregulation of SAR1A gene expression as a potential approach for the treatment of SAR1B deficiency (chylomicron retention disease) in humans.

Caspase-11/GSDMD contributes to the progression of hyperuricemic nephropathy by promoting NETs formation.

Hyperuricemia is an independent risk factor for chronic kidney disease (CKD) and promotes renal fibrosis, but the underlying mechanism remains largely unknown. Unresolved inflammation is strongly associated with renal fibrosis and is a well-known significant contributor to the progression of CKD, including hyperuricemia nephropathy. In the current study, we elucidated the impact of Caspase-11/Gasdermin D (GSDMD)-dependent neutrophil extracellular traps (NETs) on progressive hyperuricemic nephropathy. We found that the Caspase-11/GSDMD signaling were markedly activated in the kidneys of hyperuricemic nephropathy. Deletion of Gsdmd or Caspase-11 protects against the progression of hyperuricemic nephropathy by reducing kidney inflammation, proinflammatory and profibrogenic factors expression, NETs generation, α-smooth muscle actin expression, and fibrosis. Furthermore, specific deletion of Gsdmd or Caspase-11 in hematopoietic cells showed a protective effect on renal fibrosis in hyperuricemic nephropathy. Additionally, in vitro studies unveiled the capability of uric acid in inducing Caspase-11/GSDMD-dependent NETs formation, consequently enhancing α-smooth muscle actin production in macrophages. In summary, this study demonstrated the contributory role of Caspase-11/GSDMD in the progression of hyperuricemic nephropathy by promoting NETs formation, which may shed new light on the therapeutic approach to treating and reversing hyperuricemic nephropathy.

Hepatic danger signaling triggers TREM2+ macrophage induction and drives steatohepatitis via MS4A7-dependent inflammasome activation.

Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), is an advanced stage of metabolic fatty liver disease. The pathogenic mechanisms of MASH center on hepatocyte injury and the ensuing immune response within the liver microenvironment. Recent work has implicated TREM2+ macrophages in various disease conditions, and substantial induction of TREM2+ NASH-associated macrophages (NAMs) serves as a hallmark of metabolic liver disease. Despite this, the mechanisms through which NAMs contribute to MASH pathogenesis remain poorly understood. Here, we identify membrane-spanning 4-domains a7 (MS4A7) as a NAM-specific pathogenic factor that exacerbates MASH progression in mice. Hepatic MS4A7 expression was strongly induced in mouse and human MASH and associated with the severity of liver injury. Whole-body and myeloid-specific ablation of Ms4a7 alleviated diet-induced MASH pathologies in male mice. We demonstrate that exposure to lipid droplets (LDs), released upon injury of steatotic hepatocytes, triggered NAM induction and exacerbated MASH-associated liver injury in an MS4A7-dependent manner. Mechanistically, MS4A7 drove NLRP3 inflammasome activation via direct physical interaction and shaped disease-associated cell states within the liver microenvironment. This work reveals the LD-MS4A7-NLRP3 inflammasome axis as a pathogenic driver of MASH progression and provides insights into the role of TREM2+ macrophages in disease pathogenesis.

Change of epidemiological characteristics of four respiratory viral infections in children before and during COVID-19 pandemic.

OBJECTIVES: Viruses are the main infectious agents of acute respiratory infections (ARIs) in children. We aim to describe the changes in epidemic characteristics of viral ARIs in outpatient children before and during the COVID-19 pandemic. PATIENTS AND METHODS: From 2017 to 2022, the results of viral detection in oral pharyngeal swabs in 479,236 children with ARIs in the outpatient department of Children's Hospital, Zhejiang University School of Medicine, were retrospectively analyzed. Viral antigens, including adenovirus (ADV), influenza A (FLUA), influenza B (FLUB) and respiratory syncytial virus (RSV) were detected by the colloidal gold method. RESULTS: The median age was 3.4 (1.6-5.6) years. Among all the children, 159,895 cases (33.4 %) were positive for at least one virus. The total positive rate for ADV, FLUA and FLUB during the pandemic period was lower than during the pre-pandemic period in every season (pre-pandemic period vs. pandemic period11.7 % vs. 4.7 %, 13.9 % vs. 9.2 %, 7.0 % vs. 5.2 %, respectively, with overall p value < 0.001). However, the positive rate fir RSV was not significantly different between the pre-pandemic period and the pandemic period (5.6 % vs. 5.8 %, p = 0.117). Atypical timing of RSV (summer-autumn 2021) and FLUA (summer 2022) was noted. CONCLUSIONS: Public health interventions for different pathogens are maximally effective. While positive rates for ADV, FLUA and FLUB decreased during the COVID-19 pandemic period, positive rates for RSV remained similar. In RSV and FLUA, off-season outbreaks were observed. Measures need to be taken to protect children from possible infection surges due to immunity debt having accrued over the last three years.

Tissue distribution of metabolites in Cordyceps cicadae determined by DESI-MSI analysis.

In this paper, we establish an in situ visualization analysis method to image the spatial distribution of metabolites in different parts (sclerotium, coremium) and different microregions of Cordyceps cicadae (C. cicadae) to achieve the in situ visual characterization of tissues for a variety of metabolites such as nucleosides, amino acids, polysaccharides, organic acids, fatty acids, and so on. The study included LC-MS chemical composition identification, preparation of C. cicadae tissue sections, DEDI-MSI analysis, DESI combined with Q-TOF/MS to obtain high-resolution imaging of mass-to-charge ratio and space, imaging of C. cicadae in positive-negative ion mode with a spatial resolution of 100 µm, and localizing and identifying its chemical compositions based on its precise mass. A total of 62 compounds were identified; nucleosides were mainly distributed in the coremium, L-threonine and DL-isoleucine, and other essential amino acids; peptides were mainly distributed in the sclerotium of C. cicadae; and the rest of the amino acids did not have a clear pattern; sugars and sugar alcohols were mainly distributed in the coremium of C. cicadae; organic acids and fatty acids were distributed in the nucleus of C. cicadae more than in the sclerotium, and the mass spectrometry imaging method is established in the research. The mass spectrometry imaging method established in this study is simple and fast and can visualize and analyse the spatial distribution of metabolites of C. cicadae, which is of great significance in characterizing the metabolic network of C. cicadae, and provides support for the quality evaluation of C. cicadae and the study of the temporal and spatial metabolic network of chemical compounds.

Rapid authentication of characteristic milk powders by recombinase polymerase amplification assays.

The authentication of dairy species has great significance for food safety. This study focused on a more rapid method for identifying major dairy species, and specific recombinase polymerase amplification (RPA)-based assays for cattle, goat, sheep, camel and donkey were developed. Through the developed RPA-based assays, goats and sheep could be simultaneously identified and bovine families could be differentiated. The performances of the RPA assays were validated using 37 milk powder samples, of which 16.2% (6/37) were suspected of being adulterated and 24.3% (9/37) were potentially at risk of being wrongly identified as adulteration. The effectiveness of the developed assays for crude DNA detection was also validated by a rapid nucleic acid extraction kit, and results showed that the presence of large amounts of protein and fat did not affect the qualitative results. Therefore, these assays could combine with the rapid nucleic acids extraction methods for being used in field detection.

Polypeptides from traditional Chinese medicine: Comprehensive review of perspective towards cancer management.

Cancer has always been a focus of global attention, and the difficulty of treatment and poor prognosis have always plagued humanity. Conventional chemotherapeutics and treatment with synthetic disciplines will cause adverse side effects and drug resistance. Therefore, searching for a safe, valid, and clinically effective drug is necessary. At present, some natural compounds have proved to have the potential to fight cancer. Polypeptides obtained from traditional Chinese medicine are good anti-cancer ingredients. The anticancer activity has been fully demonstrated in vivo and in vitro. However, most of the functional studies on traditional Chinese medicine polypeptides are at the stage of basic experimental research, and fewer of them have been applied to clinical trials. Hence, this review mainly discusses the chemical structure, extraction, separation and purification methods, the anti-cancer mechanism, and structure-activity relationships of traditional Chinese medicine polypeptides. It provides theoretical support for strengthening the rapid separation and purification and the overall efficacy and mechanism of action, as well as the industrialization and clinical application of traditional Chinese medicine polypeptides.

GSDMD and GSDME synergy in the transition of acute kidney injury to chronic kidney disease.

BACKGROUND AND HYPOTHESIS: Acute kidney injury (AKI) could progress to chronic kidney disease (CKD) and the AKI-CKD transition has major clinical significance. A growing body of evidence has unveiled the role of pyroptosis in kidney injury. We postulate that GSDMD and GSDME exert cumulative effects on the AKI-CKD transition by modulating different cellular responses. METHODS: We established an AKI-CKD transition model induced by folic acid in wildtype (WT), Gsdmd-/-, Gsdme-/-, and Gsdmd-/-Gsdme-/- mice. Tubular injury, renal fibrosis and inflammatory responses were evaluated. In vitro studies were conducted to investigate the interplay among tubular cells, neutrophils, and macrophages. RESULTS: Double deletion of Gsdmd and Gsdme conferred heightened protection against AKI, mitigating inflammatory responses, including the formation of neutrophil extracellular traps (NETs), macrophage polarization and differentiation, and ultimately renal fibrosis, compared with wildtype mice and mice with single deletion of either Gsdmd or Gsdme. Gsdme, but not Gsdmd deficiency, shielded tubular cells from pyroptosis. GSDME-dependent tubular cell death stimulated NETs formation and prompted macrophage polarization towards a pro-inflammatory phenotype. Gsdmd deficiency suppressed NETs formation and subsequently hindered NETs-induced macrophage-to-myofibroblast transition (MMT). CONCLUSION: GSDMD and GSDME collaborate to contribute to AKI and subsequent renal fibrosis induced by folic acid. Synchronous inhibition of GSDMD and GSDME could be an innovative therapeutic strategy for mitigating the AKI-CKD transition.

Clinical Characteristics and Outcomes of AIDS-Related Burkitt Lymphoma in China: A Retrospective Single-Center Study.

Objectives: Studies on the prognosis and risk stratification of patients with acquired immune deficiency syndrome (AIDS) - related Burkitt lymphoma (AR-BL) are rare. We aim to construct a novel model to improve the risk assessment of these patients. Methods: We retrospectively analyzed the clinical data of 34 patients over the past 10 years and the factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Then, the novel model consisting of screened factors was compared with the existing models. Results: With a 37-month median follow-up, the overall 2-year PFS and OS rates were 40.50% and 36.18%, respectively. The OS of patients who received chemotherapy was better compared with those without chemotherapy (P = .0012). Treatment with an etoposide, prednisone, oncovin, cyclophosphamide, and hydroxydaunorubicin-based regimen was associated with longer OS and PFS compared with a cyclophosphamide, doxorubicin, vincristine, and prednisone-based regimen (OS, P = .0002; PFS, P = .0158). Chemotherapy (hazard ratio [HR] = 0.075; 95% confidence interval [CI], 0.009-0.614) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 to 4 (HR = 4.738; 95% CI, 1.178-19.061) were independent prognostic factors of OS in multivariate analysis and we established a novel prognostic risk stratification model named GZ8H model with chemotherapy and ECOG PS. Conclusion: GZ8H showed better stratification ability than the international prognostic index (IPI) or Burkitt lymphoma IPI (BL-IPI). Furthermore, the C-index of the nomogram used to predict OS was 0.884 in the entire cohort and the calibration curve showed excellent agreement between the predicted and actual results of OS. No human immunodeficiency virus-related factors were found to be associated with OS and PFS of AR-BL patients in our study. Overall, the clinical characteristics and outcomes in AR-BL were shown and prognostic factors for OS and PFS were identified in this study.

Synergistic mechanism of stir-baked curcumae radix with vinegar in dysmenorrhea rats based on UPLC-Q-TOF/MS metabolomics.

Curcumae Radix (i.e. Huangsiyujin: HSYJ), a well-known traditional Chinese medicine (TCM), has been widely used in clinical practice for many years to treat depression and primary dysmenorrhea. Modern pharmacological researches have demonstrated its anti-inflammatory, antidepressant, and dysmenorrhea relief effects. According to the processing theory of TCM, it is believed that stir-baked HSYJ with vinegar may enhance the ability to disperse stagnant hepatoqi and alleviate pain. However, whether the vinegar concoction of HSYJ can enhance the therapeutic effect on the Qi stagnation due to liver depression (LDQS) type of dysmenorrhea and what its mechanism has not been well explained. Based on the processing drugs theory of "stir-baked with vinegar into liver", a metabolomic approach was used to investigate the therapeutic effect and mechanism of stir-baked HSYJ with vinegar to enhance the treatment of dysmenorrhea in rats. By establishing a rat model of dysmenorrhea of the "LDQS" type, observation of hemorheology, uterine pathological sections, COX-2 and OTR protein expression and other indicators; analysis of urinary metabolic changes in rats by UPLC-Q-TOF-MS technique, to compare the differential biomarkers and metabolic pathways in the treatment of dysmenorrhea due to "liver stagnation and qi stagnation" before and after stir-baked HSYJ with vinegar. Stir-baked HSYJ with vinegar significantly inhibited the writhing response of rats, improved hemorheology, repaired damaged diseased uterus and inhibited high expression of COX-2 and OTR proteins in uterus; 68 differential metabolites were screened from the urine of rats, compared with the raw HSYJ, the levels of 14 metabolites were significantly changed in stir-baked HSYJ with vinegar, involving the pathways of phenylalanine, tyrosine and tryptophan metabolism, cysteine and methionine metabolism, aspartate and glutamate metabolism. The potentiating effect of stir-baked HSYJ with vinegar may be related to the regulation of multiple amino acid metabolic pathways.

Enantioselective Synthesis of Planar-Chiral Sulfur-Containing Cyclophanes by Chiral Sulfide Catalyzed Electrophilic Sulfenylation of Arenes.

An efficient catalytic asymmetric electrophilic sulfenylation reaction for the synthesis of planar-chiral sulfur-containing cyclophanes has been developed for the first time. This was achieved by using a new Lewis base catalyst and a new ortho-trifluoromethyl-substituted sulfenylating reagent. Using the substrates with low rotational energy barrier, the transformation proceeded through a dynamic kinetic resolution, and the high rotational energy barrier of the substrates allowed the reaction to undergo a kinetic resolution process. Meanwhile, this transformation was compatible with a desymmetrization process when the symmetric substrates were used. Various planar-chiral sulfur-containing cyclophanes were readily obtained in moderate to excellent yields with moderate to excellent enantioselectivities (up to 97 % yield and 95 % ee). This approach was used to synthesize pharmaceutically relevant planar-chiral sulfur-containing molecules. Density functional theory calculations showed that π-π interactions between the sulfenyl group and the aromatic ring in the substrate play a crucial role in enantioinduction in this sulfenylation reaction.

Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity.

BACKGROUND: Adipose-derived stem cells (ADSCs) have been extensively used in preclinical and clinical trials for treating various diseases. However, the differences between ADSCs from lean individuals (L-ADSCs) and those from obese individuals (O-ADSCs) have not been thoroughly investigated, particularly regarding their mitochondrial and lysosomal functions. Therefore, this study aims to evaluate the differences between L-ADSCs and O-ADSCs in terms of cell biological activity, mitochondria, and lysosomes. METHODS: We first isolated and cultured L-ADSCs and O-ADSCs. We then compared the differences between the two groups in terms of biological activity, including cell proliferation, differentiation potential, and their effect on the polarization of macrophages. Additionally, we observed the mitochondrial and lysosomal morphology of ADSCs using an electronic microscope, MitoTracker Red, and lysotracker Red dyes. We assessed mitochondrial function by examining mitochondrial membrane potential and membrane fluidity, antioxidative ability, and cell energy metabolism. Lysosomal function was evaluated by measuring autophagy and phagocytosis. Finally, we performed transcriptome analysis of the ADSCs using RNA sequencing. RESULTS: The biological activities of O-ADSCs were decreased, including cell immunophenotypic profiles, cell proliferation, and differentiation potential. Furthermore, compared to L-ADSCs, O-ADSCs promoted M1-type macrophage polarization and inhibited M2-type macrophage polarization. Additionally, the mitochondrial morphology of O-ADSCs was altered, with the size of the cells becoming smaller and mitochondrial fragments increasing. O-ADSCs also exhibited decreased mitochondrial membrane potential and membrane fluidity, antioxidative ability, and energy metabolism. With respect to lysosomes, O-ADSCs contained ungraded materials in their lysosomes, enhanced lysosomal permeability, and reduced autophagy and phagocytosis ability. RNA sequence analysis indicated that the signalling pathways related to cell senescence, cancer, and inflammation were upregulated, whereas the signalling pathways associated with stemness, cell differentiation, metabolism, and response to stress and stimuli were downregulated. CONCLUSIONS: This study indicates that ADSCs from individuals (BMI > 30 kg/m2) exhibit impaired mitochondrial and lysosomal function with decreased biological activity.