Gut microbiota's influence on erysipelas: evidence from a two-sample Mendelian randomization analysis.

Background: Previous studies have suggested a link between gut microbiota and skin diseases, including erysipelas, an inflammatory skin condition. Despite this, the precise nature of the relationship between erysipelas and gut microbiota remains unclear and subject to debate. Methods: We conducted a Mendelian Randomization (MR) analysis using publicly available summary data from genome-wide association studies (GWAS) to explore the potential causal relationship between gut microbiota and erysipelas. Instrumental variables (IVs) were identified using a comprehensive set of screening methods. We then performed MR analyses primarily using the Inverse Variance Weighted (IVW) method, complemented by alternative approaches such as MR Egger, weighted median, simple mode, and weighted mode. A series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test, and a leave-one-out test, were executed to ensure the robustness and validity of our findings. Results: We identified potential associations between erysipelas and various gut microbiota, including Alcaligenaceae (OR 1.23; 95% CI 1.06-1.43; p=0.006), Rikenellaceae (OR 0.77; 95% CI 0.67-0.90; p=0.001), and others. Notably, associations with Actinomyces, Lachnospiraceae NC2004 group, Ruminiclostridium 9, Ruminococcaceae UCG014, Odoribacter, and Actinobacteria were also observed. Sensitivity analyses confirmed the robustness of these associations. Conclusion: Our MR analysis suggests both potentially beneficial and harmful causal relationships between various gut microbiota and the incidence of erysipelas. This study provides new theoretical and empirical insights into the pathogenesis of erysipelas and underscores the potential for innovative preventive and therapeutic approaches.

The LANCET robotic system can improve surgical efficiency in total hip arthroplasty: A prospective randomized, multicenter, parallel-controlled clinical trial.

Objective: To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial. Methods: A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively. Results: None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications. Conclusion: The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications. The translational potential of this article: In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.

A national survey on current state and development needs of clinical and academic emergency medicine in China.

BACKGROUND: To characterize the current state of emergency medicine (EM) and the requirements for advancing EM clinical practice, education and research in China. METHODS: An anonymous electronic survey was conducted by Chinese Society of Emergency Medicine during September to October 2021. The survey contained 30 questions divided into 2 sections: the current state of EM development and the requirements for EM growth. RESULTS: 722 hospitals were included, of 487 were Level III and 235 were Level II hospitals. We found that after 40 years of development, EM had established a mature disciplinary system and refined sub-specialties including critical care, cardiopulmonary resuscitation, toxicology, disaster and emergency rescue. In Level III hospitals, 70.8% of EDs were standardized training centers for EM residents, but master's degree program, Doctor Degree program and post-doctoral degree program was approved in only 37.8%, 8.4% and 2.9% of EDs respectively and postgraduate curriculum was available in 1/4 of EDs. Only 8% have national or provincial key laboratories. In addition to advance clinical practice, there was also a high demand to improve teaching and research capacities, mainly focusing on literature review, research design and delivery, paper writing, residency training. CONCLUSIONS: EM has built a mature discipline system and refined sub-specialties in China. Teaching and research developed parallel with clinical practice. However, there was still a lack of EM master's and doctoral programs and research capacities need to be improved. More outstanding clinical and academic training should be provided to promote the rapid growth of EM in China.

Role of the P2 × 7 receptor in neurodegenerative diseases and its pharmacological properties.

Neurodegenerative diseases seriously affect patients' physical and mental health, reduce their quality of life, and impose a heavy burden on society. However, their treatment remains challenging. Therefore, exploring factors potentially related to the pathogenesis of neurodegenerative diseases and improving their diagnosis and treatment are urgently needed. Recent studies have shown that P2 × 7R plays a crucial role in regulating neurodegenerative diseases caused by neuroinflammation. P2 × 7R is an adenosine 5'-triphosphate ligand-gated cation channel receptor present in most tissues of the human body. An increase in P2 × 7R levels can affect the progression of neurodegenerative diseases, and the inhibition of P2 × 7R can alleviate neurodegenerative diseases. In this review, we comprehensively describe the biological characteristics (structure, distribution, and function) of this gene, focusing on its potential association with neurodegenerative diseases, and we discuss the pharmacological effects of drugs (P2 × 7R inhibitors) used to treat neurodegenerative diseases.

Causal effect of gut microbiota on Gastroduodenal ulcer: a two-sample Mendelian randomization study.

Background: Gastroduodenal ulcers are associated with Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the causal relationship between gastroduodenal ulcers and gut microbiota, especially specific gut microbiota, remains unclear. Methods: We conducted an analysis of published data on the gut microbiota and Gastroduodenal ulcer using genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis was performed to determine the causal relationship between gut microbiota and Gastroduodenal ulcer. Sensitivity, heterogeneity, and pleiotropy analyses were conducted to confirm the accuracy of the research findings. Results: Our study showed that the abundance of Enterobacteriaceae, Butyricicoccus, Candidatus Soleaferrea, Lachnospiraceae NC2004 group, Peptococcus, and Enterobacteriales was negatively correlated with the risk of Gastroduodenal ulcer. Conversely, the abundance of Streptococcaceae, Lachnospiraceae UCG010, Marvinbryantia, Roseburia, Streptococcus, Mollicutes RF9, and NB1n was positively correlated with the risk of Gastroduodenal ulcer. MR analysis revealed causal relationships between 13 bacterial genera and Gastroduodenal ulcer. Conclusion: This study represents a groundbreaking endeavor by furnishing preliminary evidence regarding the potentially advantageous or detrimental causal link between the gut microbiota and Gastroduodenal ulcer, employing Mendelian Randomization (MR) analysis for the first time. These discoveries have the potential to yield fresh perspectives on the prevention and therapeutic approaches concerning Gastroduodenal ulcer, with a specific focus on the modulation of the gut microbiota.

NLRP3 inflammasome in cognitive impairment and pharmacological properties of its inhibitors.

Cognitive impairment is a multifactorial and multi-step pathological process that places a heavy burden on patients and the society. Neuroinflammation is one of the main factors leading to cognitive impairment. The inflammasomes are multi-protein complexes that respond to various microorganisms and endogenous danger signals, helping to initiate innate protective responses in inflammatory diseases. NLRP3 inflammasomes produce proinflammatory cytokines (interleukin IL-1ß and IL-18) by activating caspase-1. In this review, we comprehensively describe the structure and functions of the NLRP3 inflammasome. We also explore the intrinsic relationship between the NLRP3 inflammasome and cognitive impairment, which involves immune cell activation, cell apoptosis, oxidative stress, mitochondrial autophagy, and neuroinflammation. Finally, we describe NLRP3 inflammasome antagonists as targeted therapies to improve cognitive impairment.

Mechanotransductive receptor Piezo1 as a promising target in the treatment of fibrosis diseases.

Fibrosis could happen in every organ, leading to organic malfunction and even organ failure, which poses a serious threat to global health. Early treatment of fibrosis has been reported to be the turning point, therefore, exploring potential correlates in the pathogenesis of fibrosis and how to reverse fibrosis has become a pressing issue. As a mechanism-sensitive cationic calcium channel, Piezo1 turns on in response to changes in the lipid bilayer of the plasma membrane. Piezo1 exerts multiple biological roles, including inhibition of inflammation, cytoskeletal stabilization, epithelial-mesenchymal transition, stromal stiffness, and immune cell mechanotransduction, interestingly enough. These processes are closely associated with the development of fibrotic diseases. Recent studies have shown that deletion or knockdown of Piezo1 attenuates the onset of fibrosis. Therefore, in this paper we comprehensively describe the biology of this gene, focusing on its potential relevance in pulmonary fibrosis, renal fibrosis, pancreatic fibrosis, and cardiac fibrosis diseases, except for the role of drugs (agonists), increased intracellular calcium and mechanical stress using this gene in alleviating fibrosis.

Astragalus regulates the intestinal immune response during sepsis by mediating ILC3 proliferation through RORγt.

Background: Sepsis is a common complication of many diseases and is associated with high morbidity and mortality rates. Astragalus can improve humoral and innate immunity, inhibit inflammatory responses, and protect immune cells and organs from damage. However, to the best of our knowledge there are no reports on whether astragalus can regulate intestinal innate immune function during sepsis. Methods: In this study, a rat cecal ligation and puncture model of sepsis was used to investigate the effects of astragalus treatment, following which the apoptosis rate of lymphocytes from Peyer's patches (PP) was determined. Type 3 innate lymphoid cells (ILC3) were cultured in vitro to further evaluate the effects and mechanisms of astragalus. Results: The apoptosis level of lymphocytes from PP in rats with sepsis was significantly increased, and the number of ILC3 was significantly reduced, compared with the sham operation group, which aggravated intestinal injury and ultimately led to the death of rats. Astragalus treatment significantly inhibited the apoptosis of lymphocytes from PP, increased the number of ILC3, and improved the intestinal inflammatory environment compared to the sepsis group. RT-PCR revealed that astragalus and the retinoic acid-related orphan receptor γt (RORγt) agonist LYC-55716 both promote the expression of interleukin (IL)-17A, IL-17F, IL-22, interferon-γ, and granulocyte-macrophage colony-stimulating factor mRNA. Mechanistically, astragalus promotes the proliferation of ILC3 through RORγt, thereby reducing intestinal inflammatory damage. Conclusion: Astragalus, via RORγt, promotes the generation of ILC3, improves the inflammatory environment in rats with sepsis.

Penfluroidol Attenuates the Imbalance of the Inflammatory Response by Repressing the Activation of the NLRP3 Inflammasome and Reduces Oxidative Stress via the Nrf2/HO-1 Signaling Pathway in LPS-Induced Macrophages.

Objectives: Excessive inflammatory responses and reactive oxygen species (ROS) formation play pivotal roles in the pathogenesis of sepsis. Penfluroidol (PF), an oral long-acting antipsychotic drug, has been suggested to possess diverse biological properties, including antischizophrenia, antitumour effect, and anti-inflammatory activity. The purpose of this research was to explore the anti-inflammatory and antioxidative effects of penfluroidol on lipopolysaccharide (LPS)-related macrophages. Methods: The viability of RAW264.7 and THP-1 cells was measured by Enhanced Cell Counting Kit-8 (CCK-8). The production of nitric oxide was evaluated by the Nitric Oxide Assay Kit. The generation of pro-inflammatory monocytes was detected by qRT-PCR (quantitative real-time PCR) and ELISA (enzyme-linked immunosorbent assay). Oxidative stress was assessed by measuring ROS, malondialdehyde (MDA), and superoxide dismutase (SOD) activity. The protein expression of the Nrf2/HO-1/NLRP3 inflammasome was detected by western blotting. Results: Our results indicated that no cytotoxic effect was observed when RAW264.7 and THP-1 cells were exposed to PF (0-1 µm) and/or LPS (1 µg/ml) for 24 hr. The data showed that LPS, which was repressed by PF, facilitated the generation of the pro-inflammatory molecules TNF-α and IL-6. In addition, LPS contributed to increased production of intracellular ROS compared with the control group, whereas the administration of PF effectively reduced LPS-related levels of ROS. Moreover, LPS induced the generation of MDA and suppressed the activities of SOD. However, PF treatment strongly decreased LPS-induced MDA levels and increased SOD activities in the RAW264.7 and THP-1 cells. Furthermore, our research confirmed that penfluroidol repressed the secretion of pro-inflammatory molecules by limiting the activation of the NLRP3 inflammasome and reducing oxidative effects via the Nrf2/HO-1 signaling pathway. Conclusion: Penfluroidol attenuated the imbalance of the inflammatory response by suppressing the activation of the NLRP3 inflammasome and reduced oxidative stress via the Nrf2/HO-1 signaling pathway in LPS-induced macrophages.

Scalable biomimetic sensing system with membrane receptor dual-monolayer probe and graphene transistor arrays.

Affinity-based biosensing can enable point-of-care diagnostics and continuous health monitoring, which commonly follows bottom-up approaches and is inherently constrained by bioprobes' intrinsic properties, batch-to-batch consistency, and stability in biofluids. We present a biomimetic top-down platform to circumvent such difficulties by combining a "dual-monolayer" biorecognition construct with graphene-based field-effect-transistor arrays. The construct adopts redesigned water-soluble membrane receptors as specific sensing units, positioned by two-dimensional crystalline S-layer proteins as dense antifouling linkers guiding their orientations. Hundreds of transistors provide statistical significance from transduced signals. System feasibility was demonstrated with rSbpA-ZZ/CXCR4QTY-Fc combination. Nature-like specific interactions were achieved toward CXCL12 ligand and HIV coat glycoprotein in physiologically relevant concentrations, without notable sensitivity loss in 100% human serum. The construct is regeneratable by acidic buffer, allowing device reuse and functional tuning. The modular and generalizable architecture behaves similarly to natural systems but gives electrical outputs, which enables fabrication of multiplex sensors with tailored receptor panels for designated diagnostic purposes.

LncRNA SNHG1 knockdown inhibits hyperglycemia induced ferroptosis via miR-16-5p/ACSL4 axis to alleviate diabetic nephropathy.

BACKGROUND: Hyperglycemia accelerates the development of diabetic nephropathy (DN) by inducing renal tubular injury. Nevertheless, the mechanism has not been elaborated fully. Here, the pathogenesis of DN was investigated to seek novel treatment strategies. METHODS: A model of diabetic nephropathy was established in vivo, the levels of blood glucose, urine albumin creatinine ratio (ACR), creatinine, blood urea nitrogen (BUN), malondialdehyde (MDA), glutathione (GSH), and iron were measured. The expression levels were detected by qRT-PCR and Western blotting. H&E, Masson, and PAS staining were used to assess kidney tissue injury. The mitochondria morphology was observed by transmission electron microscopy (TEM). The molecular interaction was analyzed using a dual luciferase reporter assay. RESULTS: SNHG1 and ACSL4 were increased in kidney tissues of DN mice, but miR-16-5p was decreased. Ferrostatin-1 treatment or SNHG1 knockdown inhibited ferroptosis in high glucose (HG)-treated HK-2 cells and in db/db mice. Subsequently, miR-16-5p was confirmed to be a target for SNHG1, and directly targeted to ACSL4. Overexpression of ACSL4 greatly reversed the protective roles of SNHG1 knockdown in HG-induced ferroptosis of HK-2 cells. CONCLUSIONS: SNHG1 knockdown inhibited ferroptosis via the miR-16-5p/ACSL4 axis to alleviate diabetic nephropathy, which provided some new insights for the novel treatment of diabetic nephropathy.

Body mass index and clinical outcomes in patients with heart failure with preserved ejection fraction mediated by diastolic blood pressure status?

Background: The "obesity paradox" has been elucidated in patients with heart failure (HF). Current guidelines introduce a target diastolic blood pressure (DBP) < 80 mmHg but >70 mmHg in HF patients. Due to reduced coronary perfusion, low DBP has a deleterious impact on cardiovascular outcomes. This present study aimed to assess the relationship between BMI and adjudicated clinical outcomes in HFpEF patients according to the status of DBP. Methods: We analyzed the data in 1749 HFpEF patients from the Americas of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) Trial. The population was stratified by DBP (<70 mmHg, and ≥70 mmHg) and BMI strata (normal weight, overweight, and obesity). Cox proportional hazards models and competing-risks regression analysis were performed. Results: At baseline, the median BMI and DBP were 32.9 kg/m2 (interquartile range 28.0-38.5 kg/m2) and 70 mmHg (interquartile range 62-80 mmHg), respectively. In the multivariable analysis, obesity was associated with better survival rates in the total HFpEF population (all-cause death: HR = 0.439, 95% CI 0.256-0.750; and cardiovascular death: HR = 0.378, 95% CI 0.182-0.787). In patients with DBP<70 mmHg, obesity was not significantly associated with reduced risks for all-cause death (HR = 0.531, 95% CI: 0.263-1.704) and cardiovascular death (HR = 0.680, 95% CI: 0.254-1.819). However, multivariate analyses for cardiovascular death (HR = 0.339, 95% CI: 0.117-0.983) and all-cause death (HR = 0.389, 95% CI: 0.156-0.969) were significant in patients with DBP≥70 mmHg. Nevertheless, there were no interactions between DBP and BMI. Conclusions: The obesity paradox was observed in patients with HFpEF, regardless of DBP strata (<70 mmHg, and ≥70 mmHg).

P2Y12 receptor involved in the development of chronic nociceptive pain as a sensory information mediator.

Direct or indirect damage to the nervous system (such as inflammation or tumor invasion) can lead to dysfunction and pain. The generation of pain is mainly reflected in the activation of glial cells and the abnormal discharge of sensory neurons, which transmit stronger sensory information to the center. P2Y12 receptor plays important roles in physiological and pathophysiological processes including inflammation and pain. P2Y12 receptor involved in the occurrence of pain as a sensory information mediator, which enhances the activation of microglia and the synaptic plasticity of primary sensory neurons, and reaches the higher center through the ascending conduction pathway (mainly spinothalamic tract) to produce pain. While the application of P2Y12 receptor antagonists (PBS-0739, AR-C69931MX and MRS2359) have better antagonistic activity and produce analgesic pharmacological properties. Therefore, in this article, we discussed the role of the P2Y12 receptor in different chronic pains and its use as a pharmacological target for pain relief.

Analysis of Important Volatile Organic Compounds and Genes Produced by Aroma of Pepper Fruit by HS-SPME-GC/MS and RNA Sequencing.

Pepper is an important condiment, and its aroma affects its commercial value. In this study, transcriptome sequencing and combined headspace solid-phase microextraction and gas chromatography-mass spectrometry (HS-SPME-GC-MS) were used to analyze the differentially expressed genes and volatile organic compounds in spicy and non-spicy pepper fruits. Compared with non-spicy fruits, there were 27 up-regulated volatile organic compounds (VOCs) and 3353 up-regulated genes (Up-DEGs) in spicy fruits. The results of KEGG enrichment analysis of the Up-DEGs combined with differential VOCs analysis showed that fatty acid biosynthesis and terpenoid biosynthesis may be the main metabolic pathways for aroma differences between non-spicy and spicy pepper fruits. The expression levels of the fatty acid biosynthesis-related genes FAD, LOX1, LOX5, HPL, and ADH and the key terpene synthesis gene TPS in spicy pepper fruits were significantly higher than those in non-spicy pepper fruits. The differential expression of these genes may be the reason for the different aroma. The results can provide reference for the development and utilization of high-aroma pepper germplasm resources and the breeding of new varieties.

A necroptosis gene signature predicts prostate cancer recurrence, and is linked to somatic mutation, therapeutic landscape, and immune infiltration.

OBJECTIVE: Necroptosis, a type of programmed necrotic cell death, has been implicated in cancer biology and therapeutics. Improved risk stratification is required for prostate carcinoma in individuals. In view of the importance of necroptosis, this work proposed a necroptosis-based genetic model for recurrence prediction, and clarified its characteristics. METHODS: A least absolute shrinkage and selection operator (LASSO) regression analysis was conducted based upon transcriptome data of necroptosis genes with clinical information in the Cancer Genome Atlas (TCGA) prostate carcinoma samples, which were externally verified in the GSE116918 cohort. Somatic mutation was characterized by Maftools method. The drug sensitivity was estimated via OncoPredict algorithm. T-cell inflammation score and tumor mutational burden (TMB) score were computed for inferring immunotherapy response. CIBERSORT was adopted for scoring the infiltration of immune cell compositions. RESULTS: The necroptosis gene model was defined, composed of BCL2, BCL2L11, BNIP3, CASP8, CYLD, HDAC9, IDH2, IPMK, MYC, PLK1, TNF, TNFRSF1A, and TSC1. Considering external verification, this model effectively predicted recurrence-free survival, notably within one year (area under the curve (AUC) = 0.841, 0.706, 0.776, and 0.893 in the discovery, verification, total and external independent sets, respectively). Patients who had a risk score > median value were defined as high risk, while those who had risk score ≤ median value were defined as low risk. Older age, more advanced T, N, M stage, shorter disease-free survival, and more recurred/progressed statuses were found in high-risk patients (all P<0.05). Moreover, the signature independently predicted patient recurrence (P<0.05). High-risk specimens had more frequent somatic mutation, especially of TP53, BSN, APC, TRANK1, DNAH9, and SALL1 (all P<0.05). The heterogeneity in sensitivity to small-molecule compounds was investigated in low- and high-risk patients. Also, high-risk individuals responded better to immunotherapy (P<0.05). CONCLUSION: Altogether, the necroptosis gene signature may effectively predict prostatic carcinoma recurrence and therapeutic responses, but its clinical feasibility must be verified.

Bioinformatics analysis based on crucial genes of endothelial cells in rheumatoid.

Objectives: Synovial neovascularization is an early and remarkable event that promotes the development of rheumatoid arthritis (RA) synovial hyperplasia. This study aimed to find potential diagnostic markers and molecular therapeutic targets for RA at the mRNA molecular level. Method: We download the expression profile dataset GSE46687 from the gene expression ontology (GEO) microarray, and used R software to screen out the differentially expressed genes between the normal group and the disease group. Then we performed functional enrichment analysis, used the STRING database to construct a protein-protein interaction (PPI) network, and identify candidate crucial genes, infiltration of the immune cells and targeted molecular drug. Results: Rheumatoid arthritis datasets included 113 differentially expressed genes (DEGs) including 104 upregulated and 9 downregulated DEGs. The enrichment analysis of genes shows that the differential genes are mainly enriched in condensed chromosomes, ribosomal subunits, and oxidative phosphorylation. Through PPI network analysis, seven crucial genes were identified: RPS13, RPL34, RPS29, RPL35, SEC61G, RPL39L, and RPL37A. Finally, we find the potential compound drug for RA. Conclusion: Through this method, the pathogenesis of RA endothelial cells was further explained. It provided new therapeutic targets, but the relationship between these genes and RA needs further research to be validated in the future.

Nesfatin-1 suppresses autophagy of chondrocytes in osteoarthritis via remodeling of cytoskeleton and inhibiting RhoA/ROCK signal pathway.

Autophagy and cytoskeleton integrity of chondrocytes are a considered as major factors in the progression of osteoarthritis (OA) involving excessive chondrocyte apoptosis and senescence. Nesfatin-1, an adipokine, has been reported to be closely related to cell autophagy and cytoskeleton malfunction. Our previous study found that nesfatin-1 was highly correlated with OA progress in OA patient, and the expression of nesfatin-1 rises in knee articular tissue, serum and chondrocytes. In current study, we aimed to explore the therapeutic effect of nesfatin-1 on OA and its molecular mechanism related to chondrocyte autophagy and cytoskeleton malfunction. We firstly demonstrated that nesfatin-1 effectively suppressed excessive autophagy of OA chondrocytes at both gene and protein levels. Meanwhile, we also found that nesfatin-1 significantly improved cytoskeleton integrity by showing higher F-actin/G-actin ratio, as well as more organized actin fiber structure. Mechanistically, utility of RhoA activator and inhibitor revealed that regulation of autophagy and cytoskeleton integrity via nesfatin-1 was realized via RhoA/ROCK pathway. We also confirmed that nesfatin-1 significantly ameliorated IL-1ß induced cartilage degeneration via destabilization of the medial meniscus (DMM) model. Overall, our study indicates that nesfatin-1 might be a promising therapeutic molecule for OA intervention.

Hsp22 pretreatment protects against LPS-induced hippocampal injury by alleviating neuroinflammation and apoptosis by regulating the NLRP3/Caspase1/IL-1ß signaling pathway in mice.

Neuroinflammation is an important reason for the occurrence and development of cognitive impairment. The Lentiviral vector Hsp22 was constructed for intracerebroventricular injection pretreatment, LPS was used to induce the cognitive impairment model in mice, and the Morris water maze was used to examine the changes in cognitive behavior in mice. LPS was used to induce BV-2 microglial cells, and plasmid pretreatment was used to overexpress Hsp22. HE staining, Nissl staining, immunohistochemistry, immunofluorescence, ELISA and protein blotting were used to examine microglial activation, changes in inflammatory factors, changes in pathway proteins and apoptosis. The results showed that LPS induced microglial expression of NLRP3/Caspase-1/IL-1ß signaling pathway protein Iba1, and the inflammatory protein and inflammatory factors IL-1ß, IL-6 and TNF-α, the expression of Bax increased significantly, Bcl2 expression decreased, and the learning and memory abilities of mice decreased significantly. Preconditioning with the Hsp22-overexpressing lentivirus attenuated LPS-induced activation of hippocampal microglia, the expression of inflammatory factors and pathway proteins, and apoptosis, and improved cognitive impairment in mice. In addition, plasmid-mediated Hsp22 overexpression reversed LPS-induced inflammation. These findings suggest that Hsp22 overexpression is a promising method for the treatment of cognitive impairment.

Magnetic metal-organic frameworks as adsorbents for the detection of azo pigments in food matrices.

Azo pigments with azo functional groups (-NN-) are commonly used in foods. Through rational design, here we report synthesis of a novel magnetic metal-organic framework (MOF-545) and the use of Fe3O4@MOF-545 for the selective separation of azo pigments from beverages. We find that Fe3O4@MOF-545 exhibits excellent adsorption/removal capacities for new coccine (NC, 459 mg g-1) and lemon yellow (LY, 476 mg g-1) individually. The results indicated that the adsorption capacities of Fe3O4@MOF-545 were 5 times higher than reported previously. The large surface area (120.4 m2/g) and the suitable pore size (1.6 nm) of Fe3O4@MOF-545 provided multiple accessible channels for azo pigment adsorption. The adsorption kinetics, stability, recovery, and reusability of Fe3O4@MOF-545 were all reported. The recoveries ranged from 92.9 to 104.5%, reflecting the capacity of MOF-545 to efficiently separate NC and LY. Fe3O4@MOF-545 is suitable for azo pigment determination and separation in food matrices.