Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines.

Herein, we report a visible-light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester alkylpalladium radical with the release of dinitrogen. The radical intermediate selectively adds to the double bond of a 1,3-diene or allene, followed by the allylpalladium radical-polar crossover path and selective allylic substitution with the amine substrate, thereby leading to a single unsaturated γ- or ε-amino acid derivative. This approach proceeds under mild and simple reaction conditions and shows high functional group tolerance, especially in the incorporation of various bioactive molecules. The studies on scale-up reactions and diverse derivatizations highlight the practical utility of this multicomponent reaction protocol.

Clinical and histological features of patients with chronic hepatitis B virus infection in the grey zone.

Chronic HBV infection patients who do not conform to any of the usual immune states are regarded as 'grey zone' patients. We aimed to investigate the proportion of chronic HBV infection patients in the grey zone, and evaluate the clinical characteristics and liver pathological changes in grey zone patients. Clinical data of 1391 treatment-naive chronic HBV infection patients with liver biopsy were collected. Natural history of HBV infection was determined based on European Association for the Study of the Liver (EASL) 2017, American Association for the Study of Liver Diseases (AASLD) 2018 and Chinese 2019 guidelines for the prevention and treatment of chronic HBV infection. Significant liver histological changes and associated risk factors of normal ALT grey zone patients were analysed. According to EASL, AASLD and Chinese criteria, there were 50.0%, 28% and 37.4% chronic HBV infection patients in the grey zone. Among the 353 grey zone patients with normal ALT, 72.4% had significant liver histological changes. ALT (optimal cut-off value 25 IU/L) and HBV DNA (optimal cut-off value 18,000 IU/mL) were independent risk factors of significant liver histological abnormalities. In conclusion, a substantial proportion of grey zone patients with normal ALT have significant liver histological changes that can be predicted by levels of serum ALT and HBV DNA. These results provide guidance of antiviral treatment in grey zone patients.

[Latest Findings on the Role of CD47 in Tumor Immune Evasion and Related Targeted Therapies].

CD47 is an immunoglobulin that is overexpressed on the surface of a variety of cancer cells. CD47 forms a signaling complex with signal regulatory protein alpha (SIRPα), prompting the escape of cancer cells from macrophage-mediated phagocytosis. In recent years, CD47 has been shown to be highly expressed in many types of solid tumors and is associated with poor prognosis in patients. More and more studies have shown that inhibition of the CD47-SIRPα signaling pathway can promote adaptive immune responses and enhance the phagocytosis of tumor cells by macrophages. Humanized anti-CD47 IgG4 monoclonal antibody has been studied in clinical trials for the treatment of a variety of advanced solid tumors and lymphomas, demonstrating a sound safety profile and achieving partial remission in some patients. In this review we discuss the structure and function of CD47 and the mechanism of CD47 regulation in tumors, summarize the research progress in therapeutic antibody drugs targeting CD47 and a bottleneck in research that targeted drugs are more prone to result in serious adverse effects, and evaluated the potential of the applying CD47-SIRPα signaling pathway in anti-cancer therapy.

Multicomponent Assembly of Complex Oxindoles by Enantioselective Cooperative Catalysis.

Chiral oxindoles are important chemical scaffolds found in many natural products, and their enantioselective synthesis thus attracts considerable attention. Highly diastereo- and enantioselective synthetic methods for constructing C3 quaternary oxindoles have been well-developed. However, the efficient synthesis of chiral 3-substituted tertiary oxindoles has been rarely reported due to the ease of racemization of the tertiary stereocenter via enolization. Therefore, we herein report on the multicomponent assembly (from N-aryl diazoamides, aldehydes, and enamines/indoles) of complex oxindoles by enantioselective cooperative catalysis. These reactions proceed under mild conditions and show broad substrate scope, affording the desired coupling products (>90 examples) with good to excellent stereocontrol. Additionally, this research also demonstrates the synthetic potential of this annulation by constructing the 6,6,5-tricyclic lactone core structure of Speradine A.

Mechanistic insights from targeted molecular profiling of repolarization alternans in the intact human heart.

AIMS: Action potential duration (APD) alternans is an established precursor or arrhythmia and sudden cardiac death. Important differences in fundamental electrophysiological properties relevant to arrhythmia exist between experimental models and the diseased in vivo human heart. To investigate mechanisms of APD alternans using a novel approach combining intact heart and cellular cardiac electrophysiology in human in vivo. METHODS AND RESULTS: We developed a novel approach combining intact heart electrophysiological mapping during cardiac surgery with rapid on-site data analysis to guide myocardial biopsies for laboratory analysis, thereby linking repolarization dynamics observed at the organ level with underlying ion channel expression. Alternans-susceptible and alternans-resistant regions were identified by an incremental pacing protocol. Biopsies from these sites (n = 13) demonstrated greater RNA expression in Calsequestrin (CSQN) and Ryanodine (RyR) and ion channels underlying IK1 and Ito at alternans-susceptible sites. Electrical restitution properties (n = 7) showed no difference between alternans-susceptible and resistant sites, whereas spatial gradients of repolarization were greater in alternans-susceptible than in alternans-resistant sites (P = 0.001). The degree of histological fibrosis between alternans-susceptible and resistant sites was equivalent. Mathematical modelling of these changes indicated that both CSQN and RyR up-regulation are key determinants of APD alternans. CONCLUSION: Combined intact heart and cellular electrophysiology show that regions of myocardium in the in vivo human heart exhibiting APD alternans are associated with greater expression of CSQN and RyR and show no difference in restitution properties compared to non-alternans regions. In silico modelling identifies up-regulation and interaction of CSQN with RyR as a major mechanism underlying APD alternans.

Association mapping for floral traits in cultivated Paeonia rockii based on SSR markers.

Tree peony (Paeonia Sect. Moutan) is an economically important ornamental plant, but little is known about the genetic architecture of important ornamental traits. To effectively improve ornamental value, we require a better understanding of genetic architecture in the complex traits of the tree peony. Association mapping is a powerful tool for detection of variation associated with traits. Thus, we examined the genetic diversity and the population structure of 462 unrelated cultivated P. rockii individuals, then performed association mapping to identify simple sequence repeat (SSR) markers associated with 12 floral traits. We observed a moderate level of genetic diversity (PIC = 0.459) and low linkage disequilibrium (LD) between markers, demonstrating that the potential value of an LD approach in elucidating the molecular basis of the quantitative variation in this species. An analysis of population structure revealed three subgroups in the association population. Subsequent single-marker association analysis identified 46 significant associations, involving the 11 traits with 37 SSRs. These loci explained a small proportion of the phenotypic variance, ranging from 2.68 to 23.97% (mean 5.50%). We also validated 15 of the 46 associations in a linkage mapping population of 159 individuals. Finally, five associations were further confirmed in the linkage mapping population, involving the four traits with four SSRs. These results can serve as a foundation for further analyses of the genetic architecture of floral traits, and the SSRs associated in this work have potential applications in marker-assisted breeding in tree peony.

GOLP3 is a predictor of survival in patients with hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common solid tumors and ranks the third leading cause of cancer mortality worldwide. The purpose of this study was to examine the expression dynamics of GOLPH3 in HCC tissue samples, and explore the correlation between GOLPH3 expression and prognosis in patients with HCC. METHODS: The levels of Golgi phosphoprotein 3 (GOLPH3) mRNA and protein in liver cancer cell lines and fresh tissues were determined by qRT-PCR and Western blotting. Additionally, the protein expression of GOLPH3 was detected by immunohistochemistry. RESULTS: High GOLPH3 expression was positively correlated with serum AFP level (P=0.015) and tumor recurrence or metastasis (P=0.010). In addition, liver cancer patients with high GOLPH3 expression had significantly poorer overall survival (HR, 1.87; 95% CI, 1.19-2.94; P=0.006) and poorer disease-free survival (HR, 1.90; 95% CI, 1.21-2.98; P=0.005) than those with low GOLPH3 expression. The cumulative 5-year survival rate was only 35.19% (95% CI, 26.18%-44.20%) in the high GOLPH3 expression group, whereas it was 55.93% (95% CI, 43.26%-68.60%) in the low GOLPH3 expression group. Furthermore, multivariate Cox regression analysis demonstrated that the expression of GOLPH3, tumor size and tumor multiplicity were independent prognostic predictors for HCC patients. CONCLUSION: GOLPH3 was overexpressed in HCC at both the mRNA and protein levels, and the presence of high levels of expression of GOLPH3 could serve as a novel and potential prognostic biomarker for liver cancer patients.

[Application characteristics and situation analysis of volatile oils in database of Chinese patent medicine].

Aromatic traditional Chinese medicines have a long history in China, with wide varieties. Volatile oils are active ingredients extracted from aromatic herbal medicines, which usually contain tens or hundreds of ingredients, with many biological activities. Therefore, volatile oils are often used in combined prescriptions and made into various efficient preparations for oral administration or external use. Based on the sources from the database of Newly Edited National Chinese Traditional Patent Medicines (the second edition), the author selected 266 Chinese patent medicines containing volatile oils in this paper, and then established an information sheet covering such items as name, dosage, dosage form, specification and usage, and main functions. Subsequently, on the basis of the multidisciplinary knowledge of pharmaceutics, traditional Chinese pharmacology and basic theory of traditional Chinese medicine, efforts were also made in the statistics of the dosage form and usage, variety of volatile oils and main functions, as well as the status analysis on volatile oils in terms of the dosage form development, prescription development, drug instruction and quality control, in order to lay a foundation for the further exploration of the market development situations of volatile oils and the future development orientation.

Plantaginis semen ameliorates diabetic kidney disease via targeting the sphingosine kinase 1/sphingosine-1-phosphate pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Plantaginis Semen (PS) is widely utilized as a common herb in several Asian countries, particularly China, due to its diuretic, anti-hypertensive, anti-hyperlipidemic, and anti-hyperglycemic properties. Furthermore, it is acknowledged for its ability to mitigate renal complications associated with metabolic syndrome. Despite its extensive usage, there is limited systematic literature elucidating its therapeutic mechanisms, thus emphasizing the necessity for comprehensive investigations in this field. AIM: This study aims to comprehensively evaluate the therapeutical potential of PS in treating diabetic kidney disease (DKD) and to elucidate the underlying mechanisms through in vivo and in vitro models. METHODS: The main composition of PS were characterized using the UPLC-QTOF-MS method. For the in vivo investigation, a mouse model mediated by streptozocin (STZ) associated with a high-fat diet (HFD) and unilateral renal excision was established. The mice were split into 6 groups (n = 8): control group (CON group), DKD group, low-dose of Plantago asiatica L. seed extract group (PASE-L group, 3 g/kg/d), medium-dose of PASE group (PASE-M, 6 g/kg/d), high-dose of PASE group (PASE-H, 9 g/kg/d), and positive drug group (valsartan, VAS group, 12 mg/kg/d). After 8 weeks of treatment, the damage induced by DKD was evaluated by using relevant parameters of urine and blood. Furthermore, indicators of inflammation and factors associated with the SphK1-S1P signaling pathway were investigated. For the in vitro study, the cell line HBZY-1 was stimulated by high glucose (HG), they were then co-cultured with different concentrations of PASE, and the corresponding associated inflammatory and sphingosine kinase 1/sphingosine-1-phosphate (SphK1-S1P) factors were examined. RESULTS: A total of 59 major components in PS were identified, including flavonoids, iridoids, phenylethanol glycosides, guanidine derivatives, and fatty acids. In the mouse model, PS was found to significantly improve body weight, decrease fasting blood glucose (FBG) levels, increased glucose tolerance and insulin tolerance, improved kidney-related markers compared to the DKD group, pathological changes in the kidneys also improved dramatically. These effects showed a dose-dependent relationship, with higher PASE concentrations yielding significantly better outcomes than lower concentrations. However, the effects of the low PASE concentration were not evident for some indicators. In the cellular model, the high dose of PASE suppressed high glucose (HG) stimulated renal mesangial cell proliferation, suppressed inflammatory factors and NF-κB, and decreased the levels of fibrillin-1(FN-1) and collagen IV(ColIV). CONCLUSION: Our results indicate that PS exerts favorable therapeutic effects on DKD, with the possible mechanisms including the inhibition of inflammatory pathways, suppression of mRNA levels and protein expressions of SphK1 and S1P, consequently leading to reduced overexpression of FN-1 and ColIV, thereby warranting further exploration.

Mechanic study based on untargeted metabolomics of Pi-pa-run-fei-tang on pepper combined with ammonia induced chronic cough model mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Pi-pa-run-fei-tang (PPRFT), a traditional Chinese medicine formula with long-standing history, demonstrated beneficial effect on chronic cough. However, the mechanism underlying efficacy unclear. In current research, we explored the impact and molecular mechanism of chronic cough mouse stimulating with capsaicin combined with ammonia. AIM OF THE STUDY: To investigate the metabolic modulating effects, and potential mechanisms underlying the therapeutic effect of PPRFT in chronic cough. MATERIALS AND METHODS: Chronic cough mouse models were created by stimulating mice by capsaicin combined with ammonia. Number of coughs and cough latency within 2 min were recorded. With lung tissue and serum samples collected for histopathology, metabolomics, RT-qPCR, immunohistochemistry, and WB analysis. Lymphocytes were isolated and flow cytometric assays were conducted to evaluate the differentiation between Th17 and Treg cell among CD4+ cells. RESULTS: Results indicated that PPRFT obviously reduced the number of coughs, prolonged cough latency, reduced inflammatory cell infiltration and lung tissues damage, and decreased the serum level of IL-6, IL-1ß, TNF-α, and IL-17 while increasing IL-10 levels. Notably, PPRFT suppressed Th17 cell divergence and promoted Treg cell divergence. Furthermore, serum metabolomic assays showed that 46 metabolites differed significantly between group, with 35 pathways involved. Moreover, mRNA levels of IL-6, NF-κB, IL-17, RORγT, JAK2, STAT3, PI3K and AKT in lung tissues remarkably reduced and mRNA levels of IL-10 and FOXP3 were elevated after PPRFT pretreatment. Additionally, PPRFT treatments decreased the protein levels of IL-6, NF-κB, IL-17, RORγT, p-JAK2, p-STAT3, p-PI3K, and p-AKT and increased the protein levels of IL-10 and FOXP3, but no significantly effects to the levels on JAK2, STAT3, PI3K, and AKT in the lungs. CONCLUSION: Conclusively, our result suggested the effect with PPRFT on chronic cough may be mediated through IL-6/JAK2/STAT3 and PI3K/AKT/NF-κB pathway, which regulate the differentiation between Th17 and Treg cell. This beneficial effect of PPRFT in capsaicin and ammonia-stimulated chronic cough mice indicates its potential application in treating chronic cough.

Centipeda minima and 6-O-angeloylplenolin enhance the efficacy of immune checkpoint inhibitors in non-small cell lung cancer.

BACKGROUND: Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. METHODS: We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. RESULTS: We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3ß-ß-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. CONCLUSIONS: These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.

[Preliminary study on main impacting factors on brand equity of listed traditional Chinese medicine companies].

The brand equity is valuable intangible assets of traditional Chinese medicine companies, who are excellent representatives of traditional Chinese medicine enterprises and the most promising ones to good international medicine brands. However, there is still no systematic study on how to correctly evaluate the brand equity of listed traditional Chinese medicine companies at present. To make it clear, the main impacting factors on brand equity of listed traditional Chinese medicine companies, both structured open outline pre-research and closed questionnaire research were adopted for the field survey, and some suggestions for how to protect and enhance the brand equity were also presented on the basis of survey and analysis, in the hope of improving the brand management level of listed traditional Chinese medicine companies, and making a beneficial exploration for the development of brand theory of the traditional Chinese medicine industry.

Pi-Pa-Run-Fei-Tang alleviates lung injury by modulating IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB signaling pathway and balancing Th17 and Treg in murine model of OVA-induced asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Pi-Pa-Run-Fei-Tang (PPRFT) is an empirical TCM prescription for treating asthma. However, the underlying mechanisms of PPRFT in asthma treatment have yet to be elucidated. Recent advances have revealed that some natural components could ameliorate asthma injury by affecting host metabolism. Untargeted metabolomics can be used to better understand the biological mechanisms underlying asthma development and identify early biomarkers that can help advance treatment. AIM OF THE STUDY: The aim of this study was to verification the efficacy of PPRFT in the treatment of asthma and to preliminarily explore its mechanism. MATERIALS AND METHODS: A mouse asthma model was built by OVA induction. Inflammatory cell in BALF was counted. The level of IL-6, IL-1ß, and TNF-α in BALF were measured. The levels of IgE in the serum and EPO, NO, SOD, GSH-Px, and MDA in the lung tissue were measured. Furthermore, pathological damage to the lung tissues was detected to evaluate the protective effects of PPRFT. The serum metabolomic profiles of PPRFT in asthmatic mice were determined by GC-MS. The regulatory effects on mechanism pathways of PPRFT in asthmatic mice were explored via immunohistochemical staining and western blotting analysis. RESULTS: PPRFT displayed lung-protective effects through decreasing oxidative stress, airway inflammation, and lung tissue damage in OVA-induced mice, which was demonstrated by decreasing inflammatory cell levels, IL-6, IL-1ß, and TNF-α levels in BALF, and IgE levels in serum, decreasing EPO, NO, and MDA levels in lung tissue, elevating SOD and GSH-Px levels in lung tissue and lung histopathological changes. In addition, PPRFT could regulate the imbalance in Th17/Treg cell ratios, suppress RORγt, and increase the expression of IL-10 and Foxp3 in the lung. Moreover, PPRFT treatment led to decreased expression of IL-6, p-JAK2/Jak2, p-STAT3/STAT3, IL-17, NF-κB, p-AKT/AKT, and p-PI3K/PI3K. Serum metabolomics analysis revealed that 35 metabolites were significantly different among different groups. Pathway enrichment analysis indicated that 31 pathways were involved. Moreover, correlation analysis and metabolic pathway analysis identified three key metabolic pathways: galactose metabolism; tricarboxylic acid cycle; and glycine, serine, and threonine metabolism. CONCLUSION: This research indicated that PPRFT treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating serum metabolism. The anti-asthmatic activity of PPRFT may be associated with the regulatory effects of IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB mechanistic pathways.

Diagnosis and treatment of chronic osteomyelitis based on nanomaterials.

Chronic osteomyelitis is a painful and serious disease caused by infected surgical prostheses or infected fractures. Traditional treatment includes surgical debridement followed by prolonged systemic antibiotics. However, excessive antibiotic use has been inducing rapid emergence of antibiotic-resistant bacteria worldwide. Additionally, it is difficult for antibiotics to penetrate internal sites of infection such as bone, thus limiting their efficacy. New approaches to treat chronic osteomyelitis remain a major challenge for orthopedic surgeons. Luckily, the development of nanotechnology has brought new antimicrobial options with high specificity to infection sites, offering a possible way to address these challenges. Substantial progress has been made in constructing antibacterial nanomaterials for treatment of chronic osteomyelitis. Here, we review some current strategies for treatment of chronic osteomyelitis and their underlying mechanisms.

Mechanisms of mechanically induced spontaneous arrhythmias in acute regional ischemia.

RATIONALE: Although ventricular premature beats (VPBs) during acute regional ischemia have been linked to mechanical stretch of ischemic tissue, whether and how ischemia-induced mechanical dysfunction can induce VPBs and facilitate their degradation into reentrant arrhythmias has not been yet addressed. OBJECTIVE: This study used a novel multiscale electromechanical model of the rabbit ventricles to investigate the origin of and the substrate for spontaneous arrhythmias arising from ischemia-induced electrophysiological and mechanical changes. METHODS AND RESULTS: Two stages of ischemia were simulated. Dynamic mechanoelectrical feedback was modeled as spatially and temporally nonuniform membrane currents through mechanosensitive channels, the conductances of which depended on local strain rate. Our results reveal that both strains and strain rates were significantly larger in the central ischemic zone than in the border zone. However, in both ischemia stages, a VPB originated from the ischemic border in the left ventricular apical endocardium because of mechanically induced suprathreshold depolarizations. It then traveled fully intramurally until emerging from the ischemic border on the anterior epicardium. Reentry was formed only in the advanced ischemia stage as the result of a widened temporal excitable gap. Mechanically induced delayed afterdepolarization-like events contributed to the formation of reentry by further decreasing the already reduced-by-hyperkalemia local excitability, causing extended conduction block lines and slowed conduction in the ischemic region. CONCLUSIONS: Mechanically induced membrane depolarizations in the ischemic region are the mechanism by which mechanical activity contributes to both the origin of and substrate for spontaneous arrhythmias under the conditions of acute regional ischemia.

Effects of free immunoglobulin light chains on viral myocarditis.

RATIONALE: In recent work, we have demonstrated a crucial role of mast cells in the development of viral myocarditis. Viral infection could lead to increased synthesis of free immunoglobulin light chains (FLC) and our earlier work showed that FLC can trigger mast cell activation. OBJECTIVE: We studied the possible involvement of FLC in the pathogenesis of viral myocarditis, and therapeutic effects of FLC using an animal model of viral myocarditis. METHODS AND RESULTS: DBA/2 mice were inoculated intraperitoneally with encephalomyocarditis (EMC) virus. Serum levels and concentrations in the heart of kappa FLC on day 14 in mice inoculated with EMC virus were significantly increased compared with controls. Myocardial viral concentration was significantly inhibited, the area of myocardial lesions was smaller in mice treated with kappa or lambda FLC, and survival of mice given FLC significantly improved. In contrast, an FLC antagonist deteriorated myocarditis. kappa and lambda FLC chains inhibited EMC viral replication in human amnion cells in vitro. lambda FLC significantly increased the gene expression of interleukin-10 in the heart which was previously shown to improve viral myocarditis when given exogenously. FLC also tended to increase the gene expressions of interferon-alpha and -gamma in the heart mice. CONCLUSIONS: FLC have antiviral and antiinflammatory effects and improved viral myocarditis in mice. FLC may be promising agents for the treatment of viral myocarditis.

Solitary Nasopharyngeal Metastasis From Papillary Thyroid Carcinoma Shown on FDG PET/CT.

ABSTRACT: It is very rare for papillary thyroid cancer metastasize to nasopharynx. We report FDG PET/CT findings of a solitary nasopharyngeal metastasis from papillary thyroid cancer 4 decades after the initial diagnosis in a 66-year-old woman, which mimics nasopharyngeal carcinoma. The final diagnosis was confirmed by pathological examination from the biopsy of nasopharyngeal lesion.

Integrated meta-analysis, data mining, and animal experiments to investigate the efficacy and potential pharmacological mechanism of a TCM tonic prescription, Jianpi Tongmai formula, in depression.

BACKGROUND: Depression is a common psychiatric disorder and has become a growing public health issue. Traditional Chinese medicine (TCM) tonic prescriptions have been clinically proven to be an effective treatment for depression. PURPOSE: This study aimed to identify the core prescription to improve depression among the numerous TCM tonic prescriptions. METHODS AND RESULTS: First, we used meta-analysis to clarify the efficacy and safety of tonic prescriptions in depression among 37 studies and identified 16 effective tonic prescriptions. Second, we conducted data mining to analyze the tonic prescriptions and identified important nourishing herbs. Third, based on the data mining results, we constructed a Delphi experiment to investigate the effects of these important nourishing herbs in depression. Combining the results of Delphi expert questionnaires and weight analysis, a core TCM tonic prescription, Jianpi Tongmai formula (JPTMF) for the treatment of depression, was constructed and was composed of invigorating Spleen qi herbs. Fourth, we verified that JPTMF can improve chronic unpredictable mild stress (CUMS) induced depression-like behaviors in mice. Fifth, we predicted that the mechanism of JPTMF in the treatment of depression was mainly associated with chemical synaptic transmission and neuroinflammation through network pharmacology and determined preliminary confirmation through animal experiments. CONCLUSION: This study was undertaken to evaluate the efficacy of TCM tonic prescriptions on depression and construct a core TCM tonic prescription, JPTMF, through a progressive analysis. Network pharmacology and animal experiments verified the reliability of JPTMF. The proposal of JPTMF is of innovative significance, and may provide far-reaching implications for improving depression by using nourishing herbs. Furthermore, the integrated methods applied in this study provide an innovative paradigm for the standardization and scientific basis of TCM research.

Recombinant Mosquito Densovirus with Bti Toxins Significantly Improves Pathogenicity against Aedes albopictus.

Mosquito densoviruses (MDVs) are mosquito-specific viruses that are recommended as mosquito bio-control agents. The MDV Aedes aegypti densovirus (AeDNV) is a good candidate for controlling mosquitoes. However, the slow activity restricts their widespread use for vector control. In this study, we introduced the Bacillus thuringiensis (Bti) toxin Cry11Aa domain II loop α8 and Cyt1Aa loop ß6-αE peptides into the AeDNV genome to improve its mosquitocidal efficiency; protein expression was confirmed using nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC-MS/MS). Recombinant plasmids were transfected into mosquito C6/36 cell lines, and the expression of specific peptides was detected through RT-PCR. A toxicity bioassay against the first instar Aedes albopictus larvae revealed that the pathogenic activity of recombinant AeDNV was significantly higher and faster than the wild-type (wt) viruses, and mortality increased in a dose-dependent manner. The recombinant viruses were genetically stable and displayed growth phenotype and virus proliferation ability, similar to wild-type AeDNV. Our novel results offer further insights by combining two mosquitocidal pathogens to improve viral toxicity for mosquito control.