Discovery and characterization of novel ATP citrate lyase inhibitors from Acanthopanax senticosus (Rupr. & Maxim.) Harms.

ATP citrate lyase (ACLY) is a key enzyme in glucolipid metabolism, and abnormally high expression of ACLY occurs in many diseases, including cancers, dyslipidemia and cardiovascular diseases. ACLY inhibitors are prospective treatments for these diseases. However, the scaffolds of ACLY inhibitors are insufficient with weak activity. The discovery of inhibitors with structural novelty and high activity continues to be a research hotpot. Acanthopanax senticosus (Rupr. & Maxim.) Harms is used for cardiovascular disease treatment, from which no ACLY inhibitors have ever been found. In this work, we discovered three novel ACLY inhibitors, and the most potent one was isochlorogenic acid C (ICC) with an IC50 value of 0.14 ± 0.04 µM. We found dicaffeoylquinic acids with ortho-dihydroxyphenyl groups were important features for inhibition by studying ten phenolic acids. We further investigated interactions between the highly active compound ICC and ACLY. Thermal shift assay revealed that ICC could directly bind to ACLY and improve its stability in the heating process. Enzymatic kinetic studies indicated ICC was a noncompetitive inhibitor of ACLY. Our work discovered novel ACLY inhibitors, provided valuable structure-activity patterns and deepened knowledge on the interactions between this targe tand its inhibitors.

GraphormerDTI: A graph transformer-based approach for drug-target interaction prediction.

The application of Artificial Intelligence (AI) to screen drug molecules with potential therapeutic effects has revolutionized the drug discovery process, with significantly lower economic cost and time consumption than the traditional drug discovery pipeline. With the great power of AI, it is possible to rapidly search the vast chemical space for potential drug-target interactions (DTIs) between candidate drug molecules and disease protein targets. However, only a small proportion of molecules have labelled DTIs, consequently limiting the performance of AI-based drug screening. To solve this problem, a machine learning-based approach with great ability to generalize DTI prediction across molecules is desirable. Many existing machine learning approaches for DTI identification failed to exploit the full information with respect to the topological structures of candidate molecules. To develop a better approach for DTI prediction, we propose GraphormerDTI, which employs the powerful Graph Transformer neural network to model molecular structures. GraphormerDTI embeds molecular graphs into vector-format representations through iterative Transformer-based message passing, which encodes molecules' structural characteristics by node centrality encoding, node spatial encoding and edge encoding. With a strong structural inductive bias, the proposed GraphormerDTI approach can effectively infer informative representations for out-of-sample molecules and as such, it is capable of predicting DTIs across molecules with an exceptional performance. GraphormerDTI integrates the Graph Transformer neural network with a 1-dimensional Convolutional Neural Network (1D-CNN) to extract the drugs' and target proteins' representations and leverages an attention mechanism to model the interactions between them. To examine GraphormerDTI's performance for DTI prediction, we conduct experiments on three benchmark datasets, where GraphormerDTI achieves a superior performance than five state-of-the-art baselines for out-of-molecule DTI prediction, including GNN-CPI, GNN-PT, DeepEmbedding-DTI, MolTrans and HyperAttentionDTI, and is on a par with the best baseline for transductive DTI prediction. The source codes and datasets are publicly accessible at https://github.com/mengmeng34/GraphormerDTI.

Advantages of Chinese herbal medicine in treating rheumatoid arthritis: a focus on its anti-inflammatory and anti-oxidative effects.

Oxidative stress is a condition characterized by an imbalance between the oxidative and antioxidant processes within the human body. Rheumatoid arthritis (RA) is significantly influenced by the presence of oxidative stress, which acts as a pivotal factor in its pathogenesis. Elevated levels of mitochondrial reactive oxygen species (ROS) and inflammation have been found to be closely associated in the plasma of patients with RA. The clinical treatment strategies for this disease are mainly chemical drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), glucocorticoids (GCs) and biological agents, but it is difficult for patients to accept long-term drug treatment and its side effects. In the theory of traditional Chinese medicine (TCM), RA is thought to be caused by the attack of "wind, cold, damp humor," and herbs with the effect of removing wind and dampness are used to relieve pain. Chinese herbal medicine boasts a rich heritage in effectively attenuating the symptoms of RA, and its global recognition continues to ascend. In particular, RA-relevant anti-inflammatory/anti-oxidative effects of TCM herbs/herbal compounds. The main aim of this review is to make a valuable contribution to the expanding pool of evidence that advocates for the incorporation of Chinese herbal medicine in conventional treatment plans for RA.

Fraxin Ameliorates Ulcerative Colitis by Modulating Oxidative Stress, Inflammation and TLR4/NF-κB and MAPK Signaling Pathways.

Objective: UC is a chronic gastrointestinal disorder of uncertain etiology. However, effective therapeutic drug options for UC are relatively limited. Fraxin represents a principal active constituent within the traditional Chinese medicinal herb known as Cortex Fraxini or Qinpi. Nevertheless, the impact of Fraxin on UC remains uncharted. This study aims to explore the potential of Fraxin, a key component of Cortex Fraxini, in inhibiting DSS-induced intestinal inflammation in mice and to unravel the underlying mechanisms. Methods: In vitro experiment,the RAW264. 7 cells were induced by LPS as the model.In vivo experiment,the mice were induced by DSS as the animal model for a ten day experiment.The ELISA, western blots, measurement of oxidative stress markers and other relevant methods were used to discuss the effect of Fraxin on LPS-induced RAW264.7 cells and the inhibitory effect of Fraxin on intestinal inflammation induced by DSS in mice and underlying mechanisms. Results: Our findings indicated that Fraxin significantly reduced symptoms of UC, such as body weight loss, colonic length shortening, and histological damage. At the molecular level, it inhibited ROS generation, reduced pro-inflammatory cytokines, and regulated key pathways including TLR4/NF-κB and MAPK.The findings indicated that Fraxin diminished the expression of p-NF-κB and p-IκB, downregulated iNOS and COX-2 expression, and lessened p38, JNK and ERK phosphorylation. Conclusion: Taken together, Fraxin ameliorates UC by regulating oxidative stress, inflammation, and TLR4/NF-κB and MAPK pathways, and Fraxin may be a new treatment for UC. Our findings suggest that Fraxin could offer a novel therapeutic approach for UC, targeting oxidative stress and key inflammatory pathways.

Research progress of the effective active ingredients of Astragalus mongholicus in the treatment of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent consequences of diabetes, with a high incidence and disability rate. The DPN's pathogenesis is extremely complex and yet to be fully understood. Persistent high glucose metabolism, nerve growth factor deficiency, microvascular disease, oxidative stress, peripheral nerve cell apoptosis, immune factors, and other factors have been implicated in the pathogenesis of DPN. Astragalus mongholicus is a commonly used plant used to treat DPN in clinical settings. Its rich chemical components mainly include Astragalus polysaccharide, Astragalus saponins, Astragalus flavones, etc., which play a vital role in the treatment of DPN. This review aimed to summarize the pathogenesis of DPN and the studies on the mechanism of the effective components of Astragalus mongholicus in treating DPN. This is of great significance for the effective use of Chinese herbal medicine and the promotion of its status and influence on the world.

Efficacy comparison between acupuncture and other modalities in the treatment of rotator cuff diseases: meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to analyze the efficacy of acupuncture alone or combined with physical therapy compared to other treatment interventions for relieving pain and improving function in rotator cuff diseases. METHODS: Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After PROSPERO (CRD42023396740) registration, all randomized controlled trials (RCTs) published from the inception of the databases to October 10, 2023, evaluating the efficacy of acupuncture either alone or in combination with physical therapy for treating rotator cuff diseases, were extracted from seven databases, including PubMed, Embase, the Web of Science, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), and the Wanfang Date. Two independent researchers assessed the quality of the included studies and extracted relevant data. Furthermore, a meta-analysis was conducted using Stata 14 software. RESULTS: We included 13 RCTs - 12 published in English and 1 in Chinese - that enrolled 1,371 patients. The meta-analysis results demonstrated that acupuncture alone or in combination with physical therapy was superior to other interventions for short-term shoulder joint function improvement (standardized mean difference [SMD] = -0.82, 95% confidence interval [95% CI]: -1.28 to -0.35, P = 0.001), medium-term shoulder joint function improvement (SMD = -1.00, 95% CI: -1.62 to -0.38, P = 0.002), short-term pain relief (weighted mean difference [WMD] = -1.37, 95% CI: -2.39 to -0.38, P = 0.006), medium-term pain relief (WMD = -1.66, 95% CI: -2.70 to -0.63, P = 0.002), and post-treatment shoulder joint abduction improvements (SMD = 0.68, 95% CI: 0.20 to 1.16, P = 0.005), external rotation (SMD = 0.62, 95% CI: 0.13 to 1.11, P = 0.012), and forward flexion (SMD = 0.71, 95% CI: 0.44 to 0.97, P < 0.001), with significant differences (P < 0.05). CONCLUSION: Based on the current clinical data, meta-analysis showed that acupuncture alone or combined with physical therapy is efficacious for short- and medium-term (< 3 months) pain relief and functional improvements. However, compared to other interventions, the efficacy of the long-term (3 to 12 months) period did not significantly differ. After treatment, these modalities displayed advantages such as improved shoulder joint abduction, external rotation, and forward flexion movements. However, no significant difference was noted in internal rotation movement. Thus, future studies might further investigate whether different acupuncture methods affect the efficacy of treating rotator cuff diseases and improving long-term outcome.

Inhibitory effect of acupoint electrostimulation with different layers and intensities on muscular inflammatory pain and spinal WDR neuron activity. / ç©´ä½ä¸åŒå±‚æ¬¡å’Œå¼ºåº¦ç”µåˆºæ¿€ç¼“è§£è‚Œè‚‰ç‚Žæ€§ç—›åŠå¯¹è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the analgesic effects of different levels and intensities of electrical stimulation on the local acupoints in the pain source area and their impact on wide dynamic range (WDR) neurons in the spinal dorsal horn, in order to provide a basis for selecting appropriate parameters for electroacupuncture (EA) stimulation. METHODS: Wistar rats were used in 3 parts of the experiment. Complete Freund's adjuvant was used to establish a model of inflammation-induced pain in the gastrocnemius muscle. After modeling, 6 rats were randomly selected for multi-channel extracellular electrophysiological recording of the electrical activity of WDR neurons, to determine the threshold for activating the A-component (Ta) and the C-component (Tc), which were used as the intervention intensities for skin transcutaneous electrical acupoint stimulation (TEAS) or EA. Thirty-six rats were randomly divided into normal , model , TEAS-Ta , TEAS-Tc, EA-Ta , and EA-Tc groups, with 6 rats in each group. In the pain source area , Ta or Tc intensity of TEAS or EA intervention at"Chengshan"(BL57) was performed for 30 min each time, once a day, for 3 consecutive days. A small animal pressure pain measurement instrument was used to measure the mechanical pressure pain threshold of the gastrocnemius muscle in rats, and the Von Frey filament was used to measure the mechanical pain threshold of the footpad. Thirteen rats were randomly selected to observe the immediate responsiveness of WDR neurons to Ta/Tc intensity of EA or TEAS in BL57. RESULTS: The thresholds of TEAS to activate WDR neuron A-component or C-component were (2.43±0.57) mA and (7.00±1.34) mA, respectively, while the thresholds for EA to activate muscle WDR neuron A-component or C-component were (0.72±0.34) mA and (1.58±0.35) mA, respectively. After injection of CFA into the gastrocnemius muscle, compared with the normal group both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad of rats in the model group were significantly decreased (P<0.001). After TEAS-Ta, TEAS-Tc or EA-Ta intervention in the BL57, both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad were significantly higher than those in the model group (P<0.05, P<0.001). Compared with the normal group, the electrical threshold for evoking WDR neuron C-component discharge was significantly decreased (P<0.001) in the model group, while increased after TEAS-Ta, TEAS-Tc, or EA-Ta intervention (P<0.01) compared with the model group. The evoked discharge frequency of muscle WDR neurons decreased significantly after immediate intervention with TEAS-Ta, TEAS-Tc, or EA-Ta (P<0.01, P<0.05). EA-Tc had no significant improvement on the evoked electrical activity of WDR neurons or pain behavior. CONCLUSIONS: TEAS-Ta, TEAS-Tc, or EA-Ta can all alleviate the local and footpad mechanical pain in rats with muscle inflammation and inhibit the responsiveness of WDR neurons, indicating that different intensities are required for analgesic effects at different levels of acupoints in the pain source area.

Methyl jasmonate regulation of pectin polysaccharides in Cosmos bipinnatus roots: A mechanistic insight into alleviating cadmium toxicity.

Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide.

Susceptible bacteria can survive antibiotic treatment in the mammalian gastrointestinal tract without evolving resistance.

Antibiotic resistance and evasion are incompletely understood and complicated by the fact that murine interval dosing models do not fully recapitulate antibiotic pharmacokinetics in humans. To better understand how gastrointestinal bacteria respond to antibiotics, we colonized germ-free mice with a pan-susceptible genetically barcoded Escherichia coli clinical isolate and administered the antibiotic cefepime via programmable subcutaneous pumps, allowing closer emulation of human parenteral antibiotic dynamics. E. coli was only recovered from intestinal tissue, where cefepime concentrations were still inhibitory. Strikingly, "some" E. coli isolates were not cefepime resistant but acquired mutations in genes involved in polysaccharide capsular synthesis increasing their invasion and survival within human intestinal cells. Deleting wbaP involved in capsular polysaccharide synthesis mimicked this phenotype, allowing increased invasion of colonocytes where cefepime concentrations were reduced. Additionally, "some" mutant strains exhibited a persister phenotype upon further cefepime exposure. This work uncovers a mechanism allowing "select" gastrointestinal bacteria to evade antibiotic treatment.

Analgesic efficacy of local infiltration anaesthesia versus femoral nerve block in alleviating postoperative wound pain following total knee arthroplasty: A systematic review and meta-analysis.

Total knee arthroplasty (TKA) often involves significant postoperative pain, necessitating effective analgesia. This meta-analysis compares the analgesic efficacy of local infiltration anaesthesia (LIA) and femoral nerve block (FNB) in managing postoperative wound pain following TKA. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this meta-analysis was structured around the PICO framework, assessing studies that directly compared LIA and FNB in TKA patients. A comprehensive search across PubMed, Embase, Web of Science and the Cochrane Library was conducted without time restrictions. Studies were included based on specific criteria such as participant demographics, study design and outcomes like pain scores and opioid consumption. Quality assessment utilized the Cochrane Collaboration's risk of bias tool. The statistical approach was determined based on heterogeneity, with the choice of fixed- or random-effects models guided by the I2 statistic. Sensitivity analysis and evaluation of publication bias using funnel plots and Egger's linear regression test were also conducted. From an initial pool of 1275 articles, eight studies met the inclusion criteria. These studies conducted in various countries from 2007 to 2016. The meta-analysis showed no significant difference in resting and movement-related Visual Analogue Scale scores post-TKA between the LIA and FNB groups. However, LIA was associated with significantly lower opioid consumption. The quality assessment revealed a low risk of bias in most studies, and the sensitivity analysis confirmed the stability of these findings. There was no significant publication bias detected. Both LIA and FNB are effective in controlling postoperative pain in TKA patients, but LIA offers the advantage of lower opioid consumption. Its simplicity, cost-effectiveness and opioid-sparing nature make LIA the recommended choice for postoperative analgesia in knee replacement surgeries.

A Printable Hydrogel Loaded with Medicinal Plant Extract for Promoting Wound Healing.

How to promote wound healing is still a major challenge in the healthcare while macrophages are a critical component of the healing process. Compared to various bioactive drugs, many plants have been reported to facilitate the wound healing process by regulating the immune response of wounds. In this work, a Three-dimensional (3D) printed hydrogel scaffold loaded with natural Centella asiatica extract (CA extract) is developed for wound healing. This CA@3D scaffold uses gelatin (Gel) and sodium alginate (SA) with CA extract as bio-ink for 3D printing. The CA extract contains a variety of bioactive compounds that make the various active ingredients in Centella asiatica work in concert. The printed CA@3D scaffold can fit the shape of wound, orchestrate the macrophages and immune responses within the wound, and promote wound healing compared to commercial wound dressings. The underlying mechanism of promoting wound healing is also illuminated by applying multi-omic analyses. Moreover, the CA extract loaded 3D scaffold also showed great ability to promote wound healing in diabetic chronic wounds. Due to its ease of preparation, low-cost, biosafety, and therapeutic outcomes, this work proposes an effective strategy for promoting chronic wound healing.

Integrated Computational and Experimental Framework for Inverse Screening of Candidate Antibacterial Nanomedicine.

Nanomedicine is promising for disease prevention and treatment, but there are still many challenges that hinder its rapid development. A major challenge is to efficiently seek candidates with the desired therapeutic functions from tremendously available materials. Here, we report an integrated computational and experimental framework to seek alloy nanoparticles from the Materials Project library for antibacterial applications, aiming to learn the inverse screening concept from traditional medicine for nanomedicine. Because strong peroxidase-like catalytic activity and weak toxicity to normal cells are the desired material properties for antibacterial usage, computational screening implementing theoretical prediction models of catalytic activity and cytotoxicity is first conducted to select the candidates. Then, experimental screening based on scanning probe block copolymer lithography is used to verify and refine the computational screening results. Finally, the best candidate AuCu3 is synthesized in solution and its antibacterial performance over other nanoparticles against S. aureus and E. coli. is experimentally confirmed. The results show the power of inverse screening in accelerating the research and development of antibacterial nanomedicine, which may inspire similar strategies for other nanomedicines in the future.

Strong gelation capacity of a pectin-like polysaccharide in the presence of K+ ion.

In the present study, a pectin-like apple polysaccharide (AP) obtained by metal precipitation technique was demonstrated to show strong gelling capacity in the presence of K+ ion upon cooling. Increasing amount of K+ addition monotonically promoted the gelation of AP, as characterized by the increased gelation temperature (Tgel), gel melting temperature (Tmelt) and the gel strength. Compared with K+ ion, Na+ was unable to induce AP gelation even at high ionic concentrations, but other monovalent cations (Rb+, Cs+) can induce the gelation as in the case of K+ addition. At room temperature, the minimum cationic concentration as required to induce AP gelation followed the order of K+ ≈ Cr+ (8 mM) > Rb+ (3.5 mM), indicating that cationic radius (Na+ < K+ < Rb+ < Cs+) played a dominant role in inducing AP gelation, but other factors may also be involved. Finally, the gelation behavior of AP in the presence of K+ was explained as the suppressed intermolecular electrostatic repulsion between AP chains due to the strong electrostatic shielding effect of K+, which led to the formation of a gel network mediated by intermolecular hydrogen bonding. This reported gelation property may allow AP to find application as a new gelling polysaccharide.

Optimal dietary zinc inclusion improved growth performance, serum antioxidant capacity, immune status, and liver lipid and glucose metabolism of largemouth bass (Micropterus salmoides).

This study was conducted to ascertain the effect of dietary Zn on growth and health status of juvenile largemouth bass (Micropterus salmoides). Six experimental diets with Zn level of 50.17, 56.74, 73.34, 86.03, 123.94, and 209.20 mg/kg, respectively were compounded using complex amino acid-chelated zinc, and were fed to juvenile fish (5.50 ± 0.10 g) for 70 d. The specific growth rate (SGR) varied with dietary Zn level in a quadratic model and peaked at the 73.34 mg/kg group, while the feeding rate exhibited an opposite trend (P < 0.05). The condition factor, hepatosomatic index and mesenteric fat index all exhibited a tendency similar with SGR (P < 0.05). Dietary Zn level affected serum total proteins, urea, triglycerides, and glucose (P < 0.05). Serum Zn and copper levels linearly increased with dietary Zn level, while serum iron and manganese showed the opposite trend. Serum superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) increased with dietary Zn level and reached a plateau at 86.03 mg/kg. Serum complement component 3 (C3), IgM, and lysozyme also were enhanced by 73.34 mg/kg Zn. Body protein content increased with zinc level up to 73.34 mg/kg, and then remained steadily. As dietary Zn level increased, hepatic lipid level increased and then reached a plateau at 86.03 mg/kg group, while glycogen increased linearly. Moreover, gene expression related to lipid and glycogen metabolism from liver transcriptome further explained the liver lipid and glycogen variations. To conclude, a dietary Zn requirement of 76.99 mg/kg was suggested for juvenile largemouth bass to improve growth, antioxidant capacity, and immune status.

Characterization and treatment of oily sludge: A systematic review.

Oily sludge is a prevalent hazardous waste generated in the petroleum industry, and effectively treating it remains a key challenge for the petroleum and petrochemical sectors. This paper provides an introduction to the origin, properties, and hazards of oil sludge while summarizing various treatment methods focused on reduction, recycling, and harmlessness. These methods include combustion, stabilization/solidification, oxidation and biodegradation techniques, solvent extraction, centrifugation, surfactant-enhanced oil recovery processes as well as freezing-thawing procedures. Additionally discussed are pyrolysis, microwave radiation applications along with electrokinetic method utilization for oily sludge treatment. Furthermore explored are ultrasonic radiation techniques and froth flotation approaches. These technologies have been thoroughly examined through discussions that analyze their process principles while considering influencing factors as well as advantages and disadvantages associated with each method. Based on the characteristics of oily sludge properties and treatment requirements, a selection methodology for choosing appropriate oily sludge treatment technology is proposed in this study. The development direction of processing technology has also been explored to provide guidance aimed at improving efficiency by optimizing existing processing technologies. The paper presents a comprehensive treatment method for oily sludge, ensuring that all the parameters meet the standard requirements.

New Insights into Phylogenetic Relationship of Hydrocotyle (Araliaceae) Based on Plastid Genomes.

Hydrocotyle, belonging to the Hydrocotyloideae of Araliaceae, consists of 95 perennial and 35 annual species. Due to the lack of stable diagnostic morphological characteristics and high-resolution molecular markers, the phylogenetic relationships of Hydrocotyle need to be further investigated. In this study, we newly sequenced and assembled 13 whole plastid genomes of Hydrocotyle and performed comparative plastid genomic analyses with four previously published Hydrocotyle plastomes and phylogenomic analyses within Araliaceae. The plastid genomes of Hydrocotyle exhibited typical quadripartite structures with lengths from 152,659 bp to 153,669 bp, comprising a large single-copy (LSC) region (83,958-84,792 bp), a small single-copy (SSC) region (18,585-18,768 bp), and a pair of inverted repeats (IRs) (25,058-25,145 bp). Each plastome encoded 113 unique genes, containing 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. Comparative analyses showed that the IR boundaries of Hydrocotyle plastomes were highly similar, and the coding and IR regions exhibited more conserved than non-coding and single-copy (SC) regions. A total of 2932 simple sequence repeats and 520 long sequence repeats were identified, with specificity in the number and distribution of repeat sequences. Six hypervariable regions were screened from the SC region, including four intergenic spacers (IGS) (ycf3-trnS, trnS-rps4, petA-psbJ, and ndhF-rpl32) and two coding genes (rpl16 and ycf1). Three protein-coding genes (atpE, rpl16, and ycf2) were subjected to positive selection only in a few species, implying that most protein-coding genes were relatively conserved during the plastid evolutionary process. Plastid phylogenomic analyses supported the treatment of Hydrocotyle from Apiaceae to Araliaceae, and topologies with a high resolution indicated that plastome data can be further used in the comprehensive phylogenetic research of Hydrocotyle. The diagnostic characteristics currently used in Hydrocotyle may not accurately reflect the phylogenetic relationships of this genus, and new taxonomic characteristics may need to be evaluated and selected in combination with more comprehensive molecular phylogenetic results.

Pediatric tuina for recurrent respiratory tract infection in children: A systematic review and meta-analysis.

BACKGROUND: To evaluate the effects and safety of pediatric tuina for recurrent respiratory tract infections (RRTIs). METHODS: Web of Science, PubMed, Cochrane Library, Embase, CNKI, Wanfang Data, VIP, and CBM databases were searched from inception to September 20 2023. Two authors independently selected studies, collected data, and evaluated methodological quality using the Cochrane Risk of Bias tool. Revman 5.4 was used for the meta-analysis. RESULTS: Fifteen randomized controlled trials involving 1420 pediatric patients were included in this meta-analysis. The meta-analysis indicated that pediatric tuina significantly reduced the incidence of RRTIs [MD -1.11, 95% confidence interval (CI) (-1.77, -0.46)], decreased infection duration (MD -1.16 days, 95% CI [- 1.66, - 0.66]), improved IgA (MD 0.25 g/L, 95% CI [0.09, 0.41]), IgG (MD 1.64 g/L; 95% CI [0.82, 2.45]), CD3+ (MD 3.33%, 95% CI [0.74, 5.92]), CD4+ (MD 4.78%, 95% CI [2.08, 7.48]), CD4+/CD8+ ratio (MD 0.27%, 95% CI [0.08, 0.47]), and total effective rate (RR 1.19, 95% CI [1.13, 1.25]). However, IgM levels (MD 0.26 g/L, 95% CI [-0.26, 0.81]) and CD8+ (MD -1.36%, 95% CI [- 3.12, 0.41]) were not significantly different between the groups. Moreover, no Tuina-linked adverse reactions were observed. CONCLUSION: Pediatric tuina has shown positive effects in RRTIs treatment. However, these results should be interpreted with caution owing to study quality. Further large-scale and high-quality randomized controlled trials are warranted to confirm these findings.

Research progress in arthritis treatment with the active components of Herba siegesbeckiae.

Arthritis is a group of diseases characterized by joint pain, swelling, stiffness, and limited movement. Osteoarthritis, rheumatoid arthritis, and gouty arthritis are the most common types of arthritis. Arthritis severely affects the quality of life of patients and imposes a heavy financial and medical burden on their families and society at large. As a widely used traditional Chinese medicine, Herba siegesbeckiae has many pharmacological effects such as anti-inflammatory and analgesic, anti-ischemic injury, cardiovascular protection, and hypoglycemic. In addition, it has significant therapeutic effects on arthritis. The rich chemical compositions of H. siegesbeckiae primarily include diterpenoids, sesquiterpenoids, and flavonoids. As one of the main active components of H. siegesbeckiae, kirenol and quercetin play a vital role in reducing arthritis symptoms. In the present study, the research progress in arthritis treatment with the active components of H. siegesbeckiae is reviewed.

Explore the active ingredients and potential mechanisms of JianPi QingRe HuaYu Methods in the treatment of gastric inflammation-cancer transformation by network pharmacology and experimental validation.

BACKGROUND: JianPi QingRe HuaYu Methods (JQH) have been long used to treat chronic atrophic gastritis (CAG) and precancerous lesions of gastric cancer (PLGC). However, whether JQH can inhibit the transformation of gastritis to gastric cancer (GC) remains unclear. METHODS: Herein, we first retrieved the active ingredients and targets of JQH from the TCMSP database and the targets related to the gastric inflammation-cancer transformation from public databases. Differentially expressed genes (DEGs) related to gastric inflammation-cancer transformation were identified from the Gene Expression Omnibus (GEO) database. Then, we obtained the potential therapeutic targets of JQH in treating gastric inflammation-cancer transformation by intersecting drugs and disease targets. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analyses of the potential therapeutic targets were conducted using R software. Next, we conducted molecular docking and in vitro experiments to validate our results. RESULTS: We obtained 214 potential therapeutic targets of JQH by intersecting drugs and disease targets. We found that the potential mechanisms of JQH in treating gastric inflammation-cancer transformation might be related to JAK-STAT, Wnt, p53 and VEGF signaling pathways. The molecular docking indicated that quercetin, as the main active ingredient of JQH, might inhibit gastric inflammation-cancer transformation by binding with specific receptors. Our experimental results showed that quercetin inhibited cells proliferation (P < 0.001), promoted cell apoptosis (P < 0.001), reduced the secretion of pro-inflammatory cytokines (P < 0.001) and promoted the secretion of anti-inflammatory cytokines (P < 0.001) in MNNG-induced GES-1 cells. Furthermore, quercetin inhibited cells proliferation (P < 0.001) and reduced mRNA and protein level of markers of PLGC (P < 0.001) in CDCA-induced GES-1 cells. CONCLUSION: These results provide the material basis and regulatory mechanisms of JQH in treating gastric inflammation-cancer transformation.

Nucleophilic aromatization of monoterpenes from isoprene under nickel/iodine cascade catalysis.

As a large number of organic compounds possessing two isoprene units, monoterpenes and monoterpenoids play important roles in pharmaceutical, cosmetic, agricultural, and food industries. In nature, monoterpenes are constructed from geranyl pyrophosphate (C10) via various transformations. Herein, the bulk C5 chemical-isoprene, is used for the creation of various monoterpenoids via a nucleophilic aromatization of monoterpenes under cascade catalysis of nickel and iodine. Drugs and oil mixtures from conifer and lemon can be convergently transformed to the desired monoterpenoid. Preliminary mechanistic studies are conducted to get insights about reaction pathway. Two types of cyclic monoterpenes can be respectively introduced onto two similar heterocycles via orthogonal C-H functionalization. And various hybrid terpenyl indoles are programmatically assembled from abundant C5 or C10 blocks. This work not only contributes a high chemo-, regio-, and redox-selective transformation of isoprene, but also provides a complementary approach for the creation of unnatural monoterpenoids.