The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

The therapeutic effects of traditional Chinese medicine(TCM) decoction is closely related to its decocting methods. A correct understanding of the scientific connotations of decocting methods in TCM is of great significance for guiding the application of decoctions and the development of modern TCM preparations based on decoctions. The decocting process is not only a hot water extraction process of chemical components but also accompanied by complex chemical and physical changes, forming a complex multiphase system and significantly affecting the absorption and therapeutic effect of TCM. This article reviews the research progress in scientific connotations of decocting methods in TCM from the perspectives of chemical composition changes, phase state differences,absorption behavior changes, and pharmacological and toxicological changes caused by decocting. This review is expected to provide implications for studying decocting methods and their scientific interpretation, boost the innovation and development of TCM decoctions,and promote the design and development of modern TCM preparations.
Drugs, Chinese Herbal/isolation & purification* ; Humans ; Medicine, Chinese Traditional/methods* ; Animals

The triterpenoid saponins of Centella asiatica, including asiaticoside, madecassoside, asiatic acid, and madecassic acid, are pivotal bioactive compounds of the plant. These constituents exhibit a spectrum of pharmacological activities, such as antioxidant, antitumor, and antidepressant effects, promotion of wound healing, and enhancement of microcirculation. Owing to these therapeutic properties, C. asiatica is widely employed in pharmaceutical and cosmetic industries. However, the escalating global demand for its extracts has led to potential supply shortages, prompting researchers to use multiple strategies such as multi-omics, molecular biology, and synthetic biology to conduct extensive studies. These studies encompass the elucidation of the biosynthetic pathways of triterpenoid saponins in C. asiatica, metabolic regulation, the hormonal induction of secondary metabolite synthesis, and the application of biotechnological strategies for natural product production to increase the yield of secondary metabolites in C. asiatica, or to produce active components via microbial chassis, thus satisfying market demands and promoting the sustainable exploitation of wild C. asiatica resources. This article first introduced the triterpenoid saponins of C. asiatica and their biological activities, then summarized the latest research advancements in their biosynthetic pathways, metabolic regulation, and heterologous biosynthesis, and provided an outlook on future development directions, with the aim of providing reference for comprehensive resource development and biotechnological synthesis of active components from C. asiatica.
Centella/genetics* ; Triterpenes/chemistry* ; Biosynthetic Pathways ; Humans ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts

Based on whole-genome identification of the TPS gene family in Perilla frutescens and screening, cloning, bioinformatics, and expression analysis of the synthetic enzyme for the insect-resistant component germacrene D, this study lays the foundation for understanding the biological function of the TPS gene family and the insect resistance mechanism in P. frutescens. This study used bioinformatics tools to identify the TPS gene family of P. frutescens based on its whole genome and predicted the physicochemical properties, systematic classification, and promoter cis-elements of the proteins. The relative content of germacrene D was detected in both normal and insect-infested leaves of P. frutescens, and the germacrene D synthase was screened and isolated. Gene cloning, bioinformatics analysis, and expression profiling were then performed. The results showed that a total of 99 TPS genes were identified in the genome, which were classified into the TPS-a, TPS-b, TPS-c, TPS-e/f, and TPS-g subfamilies. Conserved motif analysis showed that the TPS in P. frutescens has conserved structural characteristics within the same subfamily. Promoter cis-element analysis predicted the presence of light-responsive elements, multiple hormone-responsive elements, and stress-responsive elements in the TPS family of P. frutescens. Transcriptome data revealed that most of the TPS genes in P. frutescens were highly expressed in the leaves. GC-MS analysis showed that the relative content of germacrene D significantly increased in insect-damaged leaves, suggesting that it may act as an insect-resistant component. The germacrene D synthase gene was screened through homologous protein binding gene expression and was found to belong to the TPS-a subfamily, encoding a 64.89 kDa protein. This protein was hydrophilic, lacked a transmembrane structure and signal peptide, and was predominantly expressed in leaves, with significantly higher expression in insect-damaged leaves compared to normal leaves. In vitro expression results showed that germacrene D synthase tended to form inclusion bodies. Molecular docking showed that farnesyl pyrophosphate(FPP) fell into the active pocket of the protein and interacted strongly with six active sites. This study provides a foundation for further research on the biological functions of the TPS gene family in P. frutescens and the molecular mechanisms underlying its insect resistance.
Perilla frutescens/chemistry* ; Plant Proteins/chemistry* ; Multigene Family ; Sesquiterpenes, Germacrane/metabolism* ; Alkyl and Aryl Transferases/chemistry* ; Phylogeny ; Gene Expression Regulation, Plant

Objective Radial artery occlusion(RAO)is one of the common complications following coronary intervention via the traditional radial artery approach.This study aims to evaluate the clinical effectiveness of retrograde recanalization of occluded radial arteries through the distal transradial approach(dTRA)approach.Methods A total of 35 patients with RAO admitted to the cardiovascular department of the Anhui Chest hospital between December 2022 and April 2024,who were scheduled to undergo coronary intervention and had attempted recanalization of RAO via dTRA approach were selected.The primary result was the success rate of recanalizing RAO via dTRA.The secondary results included factors influencing the failure of recanalization via dTRA,postoperative puncture complications,and the patency rate at the 3-month follow-up.Results This study divided the patients into a successful group(29 cases,82.9％)and a failed group(6 cases,17.1％)based on whether the distal radial artery was successfully opened and occluded.The proportion of smoking(100.00％vs.17.24％,P=0.040),history of diabetes(100.00％vs.10.34％,P=0.025),and chronic total occlusion of coronary artery(83.33％vs.17.24％,P=0.030)in the failure group were higher than those in the success group,and the difference was statistically significant.The application rate of balloon tracking assisted technology in the failed group(16.67％vs.58.62％,P=0.045),and the diameter of the radial artery at 3 days after surgery[(1.63±0.13)mm vs.(2.13±0.32)mm,P=0.021]and the peak radial artery blood flow velocity at 3 days postoperatively[(0.10±0.78)m/s vs.(0.50±0.13)m/s,P＜0.001]were all lower in the successful group,and the differences were statistically significant.Logistic regression analysis 3 days after surgery showed that chronic complete occlusion of the coronary artery was an independent risk factor for surgical opening failure(OR 0.042,95％CI 0.004-0.438,P=0.008).After 3 months of follow-up,the patency rate of the successful group was 55.2％.Conclusions Retrograde recanalization of RAO via dTRA is safe and feasible,but its long-term patency rate is not high.

Lung cancer exhibits the highest incidence and mortality rates among cancers globally, with a five-year overall survival rate alarmingly below 20%. Targeting autophagy, though a controversial therapeutic strategy, is extensively employed in clinical practice. Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy. Nevertheless, the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention. This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer. It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells. Notably, most autophagy-targeting drugs, primarily natural small molecules, have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer, as opposed to inhibiting protective autophagy. These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies, offering promising approaches to combat this disease.

Objective:To observe the influence of antibacterial photodynamic therapy combined with scaling and root planning(SRP)on the periodontal condition,oral flora and C-reactive protein(CRP),prostaglandin E2(PGE2),and interleukin-8(IL-8)in gingival crevicular fluid of patients with chronic periodontitis.Methods:102 patients with chronic periodontitis who were admitted to Fengdu County People's Hospital of Chongqing from January 2023 to October 2024 were prospectively selected,they were divided into control group(received SRP treatment,51 cases)and study group(received antibacterial photodynamic therapy combined with SRP treatment,51 cases)according to random number table method.The clinical efficacy,periodontal condition,oral flora,oral health impact profile-14(OHIP-14)scores,and CRP,PGE2 and IL-8 levels in gingival crevicular fluid between two groups were compared.Result:The clinical total effective rate of the study group was higher than that of the control group(P＜0.05).Clinical attachment loss(CAL),gingival index(GI),probing depth(PD),bleeding index(BI),aggregated bacilli with release lines,fusobacterium nucleatum,porphyromonas gingivalis,OHIP-14 score,CRP,PGE2 and IL-8 levels in gingival crevicular fluid 4 weeks after treatment and 12 weeks after treatment in the study group were lower than those in the control group(P＜0.05).Conclusion:Antibacterial photodynamic therapy combined with SRP can effectively improve the periodontal condition,oral flora and CRP,PGE2,IL-8 levels in gingival crevicular fluid of patients with chronic periodontitis,and enhance clinical efficacy.

Objective:To investigate the predictive value of serum cholinesterase(CHE)and soluble growth stimula-tion gene 2 protein(sST2)for short-term death in patients with myocardial infarction and heart failure.Methods:A total of 100 patients with myocardial infarction and heart failure admitted in Nanjing Benq Hospital between March 2021 and March 2023 were screened.After 6-month follow-up,patients were grouped according to pres-ence of death.Multivariate Cox regression was used to analyze the factors associated with death during 6-month follow-up in patients with myocardial infarction and heart failure.The predictive value of CHE,sST2 and their combined detection for short-term death in patients with myocardial infarction and heart failure was analyzed by receiver operating characteristic(ROC)curve.Kaplan-Meier survival curve was used to compare short-term sur-vival rate between myocardial infarction and heart failure patients with different CHE and sST2 levels.Results:During 6-month follow-up,46 cases died.Compared to those in survival group,patients in death group had sig-nificant higher heart rate(HR)[(82.20±8.09)beats/min vs.(71.54±6.97)beats/min],mean arterial pressure(MAP)[(126.58±5.38)mmHg vs.(104.79±4.94)mmHg]and sST2[(76.48±4.82)ng/ml vs.(40.62±4.96)ng/ml],and significant lower CHE[(3.47±0.26)IU/L vs.(5.07±0.80)IU/L](P＜0.001 all).Multivariate Cox regression showed that HR(HR 1.046,95％CI 1.002～1.092,P=0.040),MAP(HR 1.988,95％CI 1.298～2.455,P＜0.001),and sST2(HR 1.068,95％CI 1.014～1.125,P=0.013)were independent risk factors for short-term death in patients with myocardial infarction and heart failure,while CHE was its independent protec-tive factor(HR=0.252,95％CI 0.145～0.561,P=0.023).ROC curve analysis indicated that the area under the curve(AUC)of CHE,sST2 and their combination for diagnosing short-term death in patients with myocardial in-farction and heart failure was 0.609(95％0.504～0.707),0.630(95％0.525～0.726)and 0.939(95％0.871～0.977)respectively,and the diagnostic efficacy of combined detection was significantly higher than CHE and sST2 alone(Z=5.814,5.524,P＜0.001 all).Kaplan-Meier survival curve showed that the survival rate of patients with low CHE level was significantly lower than that of patients with high CHE level,and the survival rate of pa-tients with high sST2 level was significantly lower than that of patients with low sST2 level(Log-rank x2=2.415,2.354,P＜0.001 all).Conclusion:CHE and sST2 were independent influencing factors for death during 6-month follow-up in patients with myocardial infarction and heart failure;their combined detection had good predictive value for short-term death in these patients.

By summarizing the mass spectrometric fragmentation patterns of oxyphenisatin substances,an analytical method was established for screening of illegally added oxyphenisatin compounds in weight-loss health foods using high performance liquid chromatography-in-source-fragmentation-quadrupole time-of-flight mass spectrometry(HPLC-ISF-QTOF-MS),along with a quantitative method for 11 kinds of oxyphenisatin compounds.Based on the developed screening method,an oxyphenisatin derivative was discovered in the reference standards,which was tentatively identified as 4-(3-(4-hydroxyphenyl)-2-oxoindolin-3-yl)phenyl acetate and confirmed by MS/MS analysis.The results showed that all 11 kinds of oxyphenisatin compounds had correlation coefficients greater than 0.9971,with limits of detection(LODs)ranging from 0.12 to 0.68 μg/L and limits of quantification(LOQ)from 0.21 to 2.29 μg/L.The LODs for 11 kinds of characteristic ions ranged from 0.45 to 9.11 μg/kg.At spiking levels of 25,50 and 100 μg/kg,the recoveries ranged from 78.9%to 117.3%.The instrumental precision,intra-day method precision and inter-day method precision were 0.23%?1.70%,0.7%?2.4%,and 1.1%?3.3%,respectively.The developed targeted and non-targeted detection method demonstrated high sensitivity,strong stability,rapid analysis,and an expanded screening range for oxyphenisatin substances,and provided robust technical support for regulatory authorities in combating illegal adulteration.

Lung cancer exhibits the highest incidence and mortality rates among cancers globally,with a five-year overall survival rate alarmingly below 20％.Targeting autophagy,though a controversial therapeutic strategy,is extensively employed in clinical practice.Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy.Nevertheless,the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention.This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer.It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells.Notably,most autophagy-targeting drugs,primarily natural small molecules,have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer,as opposed to inhibiting protective autophagy.These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies,offering promising approaches to combat this disease.