Merging total synthesis and NMR technology for deciphering the realistic structure of natural 2,6-dideoxyglycosides.

The structural identification and efficient synthesis of bioactive 2,6-dideoxyglycosides are daunting challenges. Here, we report the total synthesis and structural revision of a series of 2,6-dideoxyglycosides from folk medicinal plants Ecdysanthera rosea and Chonemorpha megacalyx, which feature pregnane steroidal aglycones bearing an 18,20-lactone and glycans consisting of 2,6-dideoxy-3-O-methyl-ß-pyranose residues, including ecdysosides A, B, and F and ecdysantheroside A. All the eight possible 2,6-dideoxy-3-O-methyl-ß-pyranoside stereoisomers (of the proposed ecdysantheroside A) have been synthesized that testify the effective gold(I)-catalyzed glycosylation methods for the synthesis of various 2-deoxy-ß-pyranosidic linkages and lays a foundation via nuclear magnetic resonance data mapping to identify these sugar units which occur promiscuously in the present and other natural glycosides. Moreover, some synthetic natural compounds and their isomers have shown promising anticancer, immunosuppressive, anti-inflammatory, and anti-Zika virus activities.

LettuceDB: an integrated multi-omics database for cultivated lettuce.

Crop genomics has advanced rapidly during the past decade, which generated a great abundance of omics data from multi-omics studies. How to utilize the accumulating data becomes a critical and urgent demand in crop science. As an attempt to integrate multi-omics data, we developed a database, LettuceDB (https://db.cngb.org/lettuce/), aiming to assemble multidimensional data for cultivated and wild lettuce germplasm. The database includes genome, variome, phenome, microbiome and spatial transcriptome. By integrating user-friendly bioinformatics tools, LettuceDB will serve as a one-stop platform for lettuce research and breeding in the future. Database URL: https://db.cngb.org/lettuce/.

Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus.

The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.

Periplogenin attenuates LPS-mediated inflammatory osteolysis through the suppression of osteoclastogenesis via reducing the NF-κB and MAPK signaling pathways.

The key target for treating inflammatory osteolysis is osteoclasts. In an inflammatory environment, osteoclast differentiation increases, and bone resorption is enhanced. Periplogenin (Ppg) is a traditional Chinese medicine. It has anti-inflammatory and antitumor effects, but its impact on inflammatory osteolysis is unknown. This study found that Ppg prevented LPS-induced skull osteolysis by inhibiting the expression of inflammatory cytokines and osteoclast production. In vitro, Ppg blocked the RANKL-induced generation of osteoclasts, the development of pseudopodia bands, and bone resorption. Ppg also attenuated the expression of NFATc1, c-Fos, CTSK, and Atp6v0d2 proteins by inhibiting the NFATc1 signaling pathway. In addition, Ppg inhibited the expression of osteoclast-specific genes, including NFATc1, c-Fos, CTSK, Atp6v0d2, and Mmp9. Moreover, Ppg also inhibited NF-κB and MAPK pathways. In vivo, Ppg reduced the number of osteoclasts on the surface of the bone and suppressed LPS-induced osteolysis of the skull. These outcomes suggest that Ppg can serve as a new alternative therapy for treating inflammatory osteolysis by inhibiting inflammation and osteoclasts.

Acupuncture Versus Oral Medications for Acute/Subacute Non-Specific Low Back Pain: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Pharmacologic intervention do not always achieve benefits in the treatment of acute/subacute non-specific low back pain (NSLBP). We assessed efficacy and safety of acupuncture for acute/subacute NSLBP as alternative treatment. RECENT FINDINGS: We searched PubMed, Web of Science, Embase, Cochrane Library, Scopus, Epistemonikos, CNKI, Wan Fang Database, VIP database, CBMLD, CSTJ, clinical trials, EUCTR, World WHO ICTRP, and ChiCTR for randomized controlled trials, cross-over studies, and cohort studies of NSLBP treated by acupuncture versus oral medication from inception to 23th April 2022. A total of 6 784 records were identified, and 14 studies were included 1 263 participants in this review. The results of the meta-analysis indicated that acupuncture therapy was slightly more effective than oral medication in improving pain (P < 0.00001, I2 = 92%, MD = -1.17, 95% CI [-1.61, -0.72]). According to the results of the meta-analysis, acupuncture therapy exhibited a significant advantage over oral medication with a substantial effect (P < 0.00001, I2 = 90%, SMD = -1.42, 95% CI [-2.22, -0.62]). Based on the results of the meta-analysis, acupuncture therapy was associated with a 12% improvement rate compared to oral medication in patients with acute/subacute NSLBP (P < 0.0001, I2 = 54%, RR = 1.11, 95% CI [1.05, 1.18]). Acupuncture is more effective and safer than oral medication in treating acute/subacute NSLBP. This systematic review is poised to offer valuable guidance to clinicians treating acute/subacute NSLBP and potentially benefit the afflicted patients. REGISTRATION: This review was registered in PROSPERO ( http://www.crd.york.ac.uk/prospero ) with registration number CRD42021278346.

Carnitine functions as an enhancer of NRF2 to inhibit osteoclastogenesis via regulating macrophage polarization in osteoporosis.

Osteoporosis, which manifests as reduced bone mass and deteriorated bone quality, is common in the elderly population. It is characterized by persistent elevation of macrophage-associated inflammation and active osteoclast bone resorption. Currently, the roles of intracellular metabolism in regulating these processes remain unclear. In this study, we initially performed bioinformatics analysis and observed a significant increase in the proportion of M1 macrophages in bone marrow with aging. Further metabolomics analysis demonstrated a notable reduction in the expression of carnitine metabolites in aged macrophages, while carnitine was not detected in osteoclasts. During the differentiation process, osteoclasts took up carnitine synthesized by macrophages to regulate their own activity. Mechanistically, carnitine enhanced the function of Nrf2 by inhibiting the Keap1-Nrf2 interaction, reducing the proteasome-dependent ubiquitination and degradation of Nrf2. In silico molecular ligand docking analysis of the interaction between carnitine and Keap1 showed that carnitine binds to Keap1 to stabilize Nrf2 and enhance its function. In this study, we found that the decrease in carnitine levels in aging macrophages causes overactivation of osteoclasts, ultimately leading to osteoporosis. A decrease in serum carnitine levels in patients with osteoporosis was found to have good diagnostic and predictive value. Moreover, supplementation with carnitine was shown to be effective in the treatment of osteoporosis.

Knowledge Graph Enhanced Transformers for Diagnosis Generation of Chinese Medicine.

Chinese medicine (CM) diagnosis intellectualization is one of the hotspots in the research of CM modernization. The traditional CM intelligent diagnosis models transform the CM diagnosis issues into classification issues, however, it is difficult to solve the problems such as excessive or similar categories. With the development of natural language processing techniques, text generation technique has become increasingly mature. In this study, we aimed to establish the CM diagnosis generation model by transforming the CM diagnosis issues into text generation issues. The semantic context characteristic learning capacity was enhanced referring to Bidirectional Long Short-Term Memory (BILSTM) with Transformer as the backbone network. Meanwhile, the CM diagnosis generation model Knowledge Graph Enhanced Transformer (KGET) was established by introducing the knowledge in medical field to enhance the inferential capability. The KGET model was established based on 566 CM case texts, and was compared with the classic text generation models including Long Short-Term Memory sequence-to-sequence (LSTM-seq2seq), Bidirectional and Auto-Regression Transformer (BART), and Chinese Pre-trained Unbalanced Transformer (CPT), so as to analyze the model manifestations. Finally, the ablation experiments were performed to explore the influence of the optimized part on the KGET model. The results of Bilingual Evaluation Understudy (BLEU), Recall-Oriented Understudy for Gisting Evaluation 1 (ROUGE1), ROUGE2 and Edit distance of KGET model were 45.85, 73.93, 54.59 and 7.12, respectively in this study. Compared with LSTM-seq2seq, BART and CPT models, the KGET model was higher in BLEU, ROUGE1 and ROUGE2 by 6.00-17.09, 1.65-9.39 and 0.51-17.62, respectively, and lower in Edit distance by 0.47-3.21. The ablation experiment results revealed that introduction of BILSTM model and prior knowledge could significantly increase the model performance. Additionally, the manual assessment indicated that the CM diagnosis results of the KGET model used in this study were highly consistent with the practical diagnosis results. In conclusion, text generation technology can be effectively applied to CM diagnostic modeling. It can effectively avoid the problem of poor diagnostic performance caused by excessive and similar categories in traditional CM diagnostic classification models. CM diagnostic text generation technology has broad application prospects in the future.

Atranorin inhibits Zika virus infection in human glioblastoma cell line SNB-19 via targeting Zika virus envelope protein.

BACKGROUND: Zika virus (ZIKV) is a single-stranded RNA flavivirus transmitted by mosquitoes. Its infection is associated with neurological complications such as neonatal microcephaly and adult Guillain-Barré syndrome, posing a serious threat to the health of people worldwide. Therefore, there is an urgent need to develop effective anti-ZIKV drugs. Atranorin is a lichen secondary metabolite with a wide range of biological activities, including anti-inflammatory, antibacterial and antioxidant, etc. However, the antiviral activity of atranorin and underlying mechanism has not been fully elucidated. PURPOSE: We aimed to determine the anti-ZIKV activity of atranorin in human glioma cell line SNB-19 and investigate the potential mechanism from the perspective of viral life cycle and the host cell functions. METHODS: We first established ZIKV-infected human glioma cells (SNB-19) model and used Western Blot, RT-qPCR, immunofluorescence, fluorescence-activated cell sorting (FACS) and plaque assay to evaluate the anti-ZIKV activity of atranorin. Then we assessed the regulation effect of atranorin on ZIKV induced IFN signal pathway activation by RT-qPCR. Afterward, we introduced time-of-addition assay, viral adsorption assay, viral internalization assay and transferrin uptake assay to define which step of ZIKV lifecycle is influenced by atranorin. Finally, we performed virus infectivity assay, molecular docking and thermal shift assay to uncover the target protein of atranorin on ZIKV. RESULTS: Our study showed that atranorin could protect SNB-19 cells from ZIKV infection, as evidenced by inhibited viral protein expression and progeny virus yield. Meanwhile, atranorin attenuated the activation of IFN signal pathway and downstream inflammatory response that induced by ZIKV infection. The results of time-of-addition assay indicated that atranorin acted primarily by disturbing the viral entry process. After ruling out the effect of atranorin on AXL receptor tyrosine kinase (AXL) dependent virus adsorption and clathrin-mediated endocytosis, we confirmed that atranorin directly targeted the viral envelope protein and lowered ZIKV infectivity by thermal shift assay and virus infectivity assay respectively. CONCLUSION: We found atranorin inhibits ZIKV infection in SNB-19 cells via targeting ZIKV envelope protein. Our study provided an experimental basis for the further development of atranorin and a reference for antiviral drug discovery from natural resources.

Evaluation of the effect of herbal agents as management of radiodermatitis in breast cancer patients: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of herbal agents in the prevention and therapy of radiodermatitis in breast cancer patients. METHODS: Randomized controlled trials were searched from databases such as PubMed, Web of Science, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) to assess the effectiveness of herbal agents compared to a standard medication or placebo in prevention or treatment of radiodermatitis in breast cancer. RESULTS: Data from 16 studies involving 1994 patients were included. This meta-analysis included 10 clinical trials of 562 breast cancer patients treated with calendula, silymarin, or aloe vera for the prevention of radiodermatitis. Silymarin showed positive effects in ameliorating the damage of radiodermatitis, whereas the efficacy of calendula and aloe vera in the treatment of radiodermatitis lacks sufficient evidence. CONCLUSIONS: Herbal medicine may show therapeutic effects on radiodermatitis in breast cancer, but more comprehensive investigations and clinical trials are required in the future.

ASTRAGALOSIDE â £ MODULATES GUT MACROPHAGES M1/M2 POLARIZATION BY RESHAPING GUT MICROBIOTA AND SHORT CHAIN FATTY ACIDS IN SEPSIS.

ABSTRACT: M1 macrophage-mediated inflammation is critical in sepsis. We previously found the protective role of astragaloside intravenous (AS-IV) in sepsis-associated gut impairment, whose specific mechanism remains unknown. Gut microbiota modulates gut homeostatic balance to avoid excessive inflammation. Here, we aimed to investigate effects of AS-IV on gut macrophages polarization and potential roles of gut microbiota and short chain fatty acids (SCFAs) in septic gut damage. Mice were pretreated by AS-IV gavage for 7 days before cecal ligation and puncture. M1 polarization of gut lamina propria macrophages (LpMs) was promoted by cecal ligation and puncture, accompanied by abnormal cytokines release and intestinal barrier dysfunction. NLRP3 inflammasome was activated in M1 LpMs. 16S rRNA sequencing demonstrated gut microbiota imbalance. The levels of acetate, propionate, and butyrate in fecal samples decreased. Notably, AS-IV reversed LpMs M1/M2 polarization, lightened gut inflammation and barrier injury, reduced NLRP3 inflammasome expression in LpMs, restored the diversity of gut microbiome, and increased butyrate levels. Similarly, these benefits were mimicked by fecal microbiota transplantation or exogenous butyrate supplementation. In Caco-2 and THP-1 cocultured model, LPS and interferon γ caused THP-1 M1 polarization, Caco-2 barrier impairment, abnormal cytokines release, and high NLRP3 inflammasome expression in THP-1 cells, all of which were mitigated by butyrate administration. However, these protective effects of butyrate were abrogated by NLRP3 gene overexpression in THP-1. In conclusion, AS-IV can ameliorate sepsis-induced gut inflammation and barrier dysfunction by modulating M1/M2 polarization of gut macrophages, whose underlying mechanism may be restoring gut microbiome and SCFA to restrain NLRP3 inflammasome activation.

Pharmacokinetic study of five components of Fuzheng Huayu tablets in healthy human plasma.

Natural medicines play a crucial role in clinical drug applications, serving as a primary traditional Chinese medicine for the clinical treatment of liver fibrosis. Understanding the in vivo metabolic process of the Fuzheng Huayu (FZHY) formula is essential for delving into its material basis and mechanism. In recent years, there has been a growing body of research focused on the mechanisms and component analysis of FZHY. This study aimed to examine the pharmacokinetics of FZHY in healthy volunteers following oral administration. Blood samples were collected at designated time intervals after the oral intake of 9.6-g FZHY tablets. A UHPLC-Q/Exactive method was developed to assess the plasma concentrations of five components post-FZHY ingestion. The peak time for all components occurred within 10 min. The peak concentration (Cmax ) values for amygdalin, schisandrin, and schisandrin A ranged from 3.47 to 28.80 ng/mL, with corresponding AUC(0-t) values ranging from 10.63 to 103.20 ng h/mL. For schisandrin B and prunasin, Cmax values were in the range of 86.52 to 229.10 ng/mL, and their AUC(0-t) values ranged from 375.26 to 1875.54 ng h/mL, indicating significant exposure within the body. These findings demonstrate that the developed method enables rapid and accurate detection and quantification of the five components in FZHY, offering a valuable reference for its clinical study.

Folic acid blocks ferroptosis induced by cerebral ischemia and reperfusion through regulating folate hydrolase transcriptional adaptive program.

Cerebral ischemia-reperfusion (I/R) injury is notably linked with folic acid (FA) deficiency. The aim of our investigation was to explore the effects and underlying mechanisms by which FA mitigates I/R, specifically through regulating the GCPII transcriptional adaptive program. Initially, we discovered that following cerebral I/R, levels of FA, methionine synthase (MTR), and methylenetetrahydrofolate reductase (MTHFR) were decreased, while GCPII expression was elevated. Secondly, administering FA could mitigate cognitive impairment and neuronal damage induced by I/R. Thirdly, the mechanism of FA supplementation involved suppressing the transcriptional factor Sp1, subsequently inhibiting GCPII transcription, reducing Glu content, obstructing cellular ferroptosis, and alleviating cerebral I/R injury. In summary, our data demonstrate that FA affords protection against cerebral I/R injury by inhibiting the GCPII transcriptional adaptive response. These findings unveil that targeting GCPII might be a viable therapeutic strategy for cerebral I/R.

TLDA: A transfer learning based dual-augmentation strategy for traditional Chinese Medicine syndrome differentiation in rare disease.

The Traditional Chinese Medicine (TCM) has demonstrated its significant medical value over the decades, particularly during the COVID-19 pandemic. TCM-AI interdisciplinary models have been proposed to model TCM knowledge, diagnosis, and treatment experiments in clinical practice. Among them, numerous models have been developed to simulate the syndrome differentiation process of human TCM doctors for automatic syndrome diagnosis. However, these models are designed for normal scenarios and trained using a supervised learning paradigm which needs tens of thousands of training samples. They fail to effectively differentiate syndromes in rare disease scenarios where the available TCM electronic medical records (EMRs) are very limited for each unique syndrome. To address the challenge of rare diseases, this study proposes a simple yet effective method called Transfer Learning based Dual-Augmentation (TLDA). TLDA aims to augment the limited EMRs at both the sample-level and feature-level, enriching the pathological and medical information during training. Extended experiments involving 11 comparison models, including the state-of-the-art model, demonstrate the effectiveness of TLDA. TLDA outperforms all comparison models by a significant margin. Furthermore, TLDA can also be extended to other medical tasks when the EMRs for diagnosis are limited in samples.

Longitudinal change in CDC42 in psoriasis: correlation with disease activity and treatment response.

Objective: To investigate longitudinal CDC42 change and its correlation with disease activity and treatment response in patients with psoriasis. Methods: This prospective study detected serum CDC42 at months (M) 0, M1, M3 and M6 in 150 patients with psoriasis with current initiation of topical therapy/phototherapy/systemic therapy. Results: CDC42 was positively related to systemic biologic treatment history (p = 0.025) but negatively associated with psoriatic area (p = 0.010) and Psoriasis Area Severity Index (PASI; p < 0.001). CDC42 continuously elevated from M0 to M6 (p < 0.001). CDC42 at M1/M3/M6 was enhanced in patients with current systemic biologic therapy and PASI 75 or 90 response at M6 versus those without (all p < 0.050). Conclusion: Increased serum CDC42 level reflects reduced disease severity and better treatment response in patients with psoriasis.

CDC42 is a protein that plays a role in inflammation and immune regulation in autoimmune diseases. CDC42 levels were detected in 150 patients with psoriasis at different time points and 150 healthy people at enrollment. The results showed that patients with psoriasis had lower CDC42 levels versus healthy people. Patients with psoriasis who received previous biologic treatments and those with smaller affected skin areas had higher CDC42 levels. Over time, CDC42 levels increased in patients with psoriasis. Patients who started biologic treatments (versus those who did not) and patients who responded better to treatment had higher CDC42 levels. The increase in CDC42 levels reflects better treatment outcomes in patients with psoriasis.

Herbal medicine formula Huazhuo Tiaozhi granule ameliorates dyslipidaemia via regulating histone lactylation and miR-155-5p biogenesis.

BACKGROUND: Huazhuo Tiaozhi granule (HTG) is a herbal medicine formula widely used in clinical practice for hypolipidaemic effects. However, the molecular mechanisms underlying dyslipidaemia treatment have not been well elucidated. RESULTS: A significant reduction in the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) was observed in the serum of patients with dyslipidaemia after HTG treatment, without disruption in the levels of aspartate transaminase (AST), alanine transaminase (ALT), urea nitrogen (BUN), and creatinine (Cr). The dyslipidaemia rat model was induced by a high-fat diet and treated with Xuezhikang (0.14 g/kg/d) or HTG (9.33 g crude herb/kg/day) by gavage for 8 weeks. Body weight and liver index were markedly decreased in dyslipidaemic rats after treatment with Xuezhikang or HTG. HTG administration markedly ameliorated hyperlipidaemia by decreasing the levels of TC and LDL-C in serum and hepatic lipid accumulation. In vitro, lipid accumulation in LO2 and HepG2 cells was alleviated by serum treatment with HTG. High lactylation was observed in 198 proteins, including lactylation of histone H2B (K6), H4 (K80). Deep sequencing of microRNAs showed that miR-155-5p was significantly downregulated. CONCLUSIONS: This study demonstrates that HTG is an effective and safe formula for treating dyslipidaemia, which promotes lactylation in hepatocytes, and the retardation of miR-155-5p biogenesis.

Current Status of Research on Tuina for Analgesia: A Bibliometric and Visual Analysis.

Purpose: Tuina is a nonpharmacological modality for pain relief that has found applications in the treatment of several pain disorders. Tuina analgesia has been increasingly studied; however, few studies have focused on the previous publication trends, prevalent research areas, collaborations, and other factors. This study aimed to systematically analyze research trends and hot topics in the field of tuina analgesia over the past 30 years, using bibliometric analysis, to inform future research. Methods: The web of science database was searched for literature on tuina analgesia from 1992-2023. VOSviewer and CiteSpace were used to analyze annual publication volumes, countries, institutions, journals and CO-cited journals, authorship, articles, and keywords and their relevance, and to perform co-occurrence and clustering analyses. Results: A total of 621 literature elements were included in the analysis. The annual volume of publications has increased steadily in recent years. The top three high-yielding countries were the United States, China, and Canada, respectively. The top three institutional outputs were from Shanghai University of Chinese medicine, Beijing University of Chinese medicine, and McMaster University, respectively. Notably, there was an imbalance between national outputs and centrality, with higher centrality in the United States (0.35) and lower in China (0.01). Cochrane Database of Systematic Reviews was the journal with the most publications (22), and PAIN was the most influential co-cited journals (publications=306). Moreover, current research in this field was dominated by studies on Tuina for relieving postoperative pain, the effectiveness of Tuina analgesia, and Tuina treatment for pain accompanied by anxiety. Conclusion: This study employed bibliometrics to analyze the literature on Tuina for pain treatment over a 30-year period, identifying potential collaborators, institutions, hot topics, and future research trends that will inform potential future directions.

Duhuo Jisheng decoction alleviates neuroinflammation and neuropathic pain by suppressing microglial M1 polarization: a network pharmacology research.

BACKGROUND: Neuropathic pain (NP) is the most prevalent form of chronic pain resulting from nerve damage or injury. Despite the widespread use of Duhuo Jisheng decoction (DHJSD) in traditional Chinese medicine (TCM) to treat chronic pain, the mechanism underlying its analgesic action remains unclear. METHODS: Using network pharmacology, we obtained DHJSD and NP-related target information from public databases to construct protein-protein interactions (PPI) and compound-target networks based on common target genes. These networks were further analyzed using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG). The interaction between molecules was verified through molecular docking using AutoDock Tools software. Additionally, we treated a chronic constriction injury (CCI) rat model with DHJSD and determined the mechanical withdrawal threshold (MWT). We used an enzyme-linked immunosorbent assay kit to determine the levels of inflammatory cytokines. Furthermore, qRT-PCR was employed to analyze ACHE, NOS2, MAPK3, PTGS2, AKT1, and PPARG mRNA expression, and immunofluorescence was used to evaluate changes in microglia. RESULTS: Our screening of compounds and targets identified 252 potential targets of DHJSD associated with NP. PPI analysis, along with GO and KEGG analyses, revealed that the potential mechanism of DHJSD in NP treatment may be related to inflammatory reactions, the IL-17 signaling pathway, MAP kinase activity, and endocrine activity. Based on molecular docking, the core target showed significant affinity for DHJSD's active components. Moreover, DHJSD treatment repaired the CCI-induced inflammatory reaction in the spinal cord while regulating the expression of ACHE, NOS2, MAPK3, PTGS2, AKT1, and PPARG mRNA. Immunofluorescence results indicated that the active components of DHJSD may regulate microglial M1 polarization to improve neuroinflammation, PPARG may have been involved in the process. CONCLUSION: The multi-component, multi-target, and multi-pathway actions of DHJSD provide new insights into its therapeutic mechanism in NP.

Acupuncture for Low Back Pain: Reevaluation of Systematic Reviews and Meta-analyses.

PURPOSE OF REVIEW: This overview aims to reevaluate the methodological quality, report quality, and evidence quality of systematic reviews (SRs)/meta-analyses (MAs) of acupuncture for low back pain to determine whether acupuncture effectively treats low back pain (LBP). RECENT FINDINGS: Twenty-three SRs/MAs were deemed eligible for the present overview. The AMSTAR 2 score showed that the methodological quality of one SR/MA was of medium quality, one was of low quality, and 21 were of critically low quality. Based on the results of the PRISMA evaluation, there are certain areas for improvement in the quality of reporting of SRs/MAs. There were some reporting flaws in the topic of search strategy (8/23, 34.78%), certainty assessment (4/23, 17.39%), the certainty of evidence (4/23, 17.39%), registration and protocol (3/23, 13.04%), and availability of data, code, and other material (1/23, 4.35%). Results from the GRADE evaluation indicated that 13 of 255 outcomes were rated as moderate, 88 were low, and 154 were very low. Acupuncture effectively treated LBP in the SRs/MAs included in the reevaluation. However, the methodological, report, and evidence-based quality of the SRs/MAs on acupuncture for LBP was low. Therefore, further rigorous and comprehensive studies are warranted to improve the quality of SRs/MAs in this field.

Effect of solar proton events on test mass for gravitational wave detection in the 24th solar cycle.

Free-falling cubic Test Masses (TMs) are a key component of the interferometer used for low-frequency gravitational wave (GW) detection in space. However, exposure to energetic particles in the environment can lead to electrostatic charging of the TM, resulting in additional electrostatic and Lorentz forces that can impact GW detection sensitivity. To evaluate this effect, the high-energy proton data set of the Geostationary Operational Environmental Satellite (GOES) program was used to analyze TM charging due to Solar Proton Events (SPEs) in the 24th solar cycle. Using the Geant4 Monte Carlo toolkit, the TM charging process is simulated in a space environment for SPEs falling into three ranges of proton flux: (1) greater than 10 pfu and less than 100 pfu, (2) greater than 100 pfu and less than 1000 pfu, and (3) greater than 1000 pfu. It is found that SPEs charging can reach the threshold within 535 s to 18.6 h, considering a reasonable discharge threshold of LISA and Taiji. We demonstrate that while there is a somewhat linear correlation between the net charging rate of the TM and the integrated flux of [Formula: see text] 10 MeV SPEs, there are many cases in which the integrated flux is significantly different from the charging rate. Therefore, we investigate the difference between the integral flux and the charging rate of SPEs using the charging efficiency assessment method. Our results indicate that the energy spectrum structure of SPEs is the most important factor influencing the charging rate. Lastly, we evaluate the charging probability of SPEs in the 24th solar cycle and find that the frequency and charging risk of SPEs are highest in the 3rd, 4th, 5th, 6th, and 7th years, which can serve as a reference for future GW detection spacecraft.

Formononetin improves the inflammatory response and bone destruction in knee joint lesions by regulating the NF-kB and MAPK signaling pathways.

Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti-inflammatory effects, as well as, many other biological activities. Existing evidence has aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF-κB ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF-κB signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL-1ß, FMN inhibited the NF-κB signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low- and high-dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high-dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury.