Gut dysbiosis impairs intestinal renewal and lipid absorption in Scarb2 deficiency-associated neurodegeneration.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease (GD) and Parkinson's disease (PD). Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.

Fuling production areas in China: climate and distribution changes (A.D. 618-2100).

Through a meticulous analysis of ancient Chinese literature, this study comprehensively documents the geographical distribution of Fuling, a traditional Chinese medicinal material, during the Tang, Song, Ming, and Qing dynasties spanning from the seventh to the twentieth century in China. Based on the contemporary distribution information of Fuling, we utilized the maximum entropy (MaxEnt) model to simulate the suitable distribution areas of Fuling under both present-day conditions and in the future (2081~2100). The findings reveal that climate change has influenced the distribution of Fuling production areas. The shifts in Fuling's origin during different periods in ancient and modern times align with climate fluctuations and concurrent societal development. During the Tang and Song dynasties, Fuling primarily originated in northern China. However, it migrated southward during the Little Ice Age (LIA) and has recently shown a slight northward shift, in line with the climate fluctuations of the LIA and contemporary global warming trends. This study offers a comprehensive analysis of the changes in the distribution and production areas of Fuling over a 1500-year period, encompassing ancient, modern, and future periods. The results provide critical insights for adjusting Fuling cultivation areas in response to climate change and for further exploration of the mechanisms through which climate impacts the growth of Fuling.

Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method.

Cancer patients should be concerned about depression, which can negatively impact their mental health. To develop efficient therapies, it is essential to comprehend the connection between cancer and depression. This study used neuroimaging to investigate the use of mediator-deuterium acupuncture (MDA) for people with cancer-induced depression and its effects on brain regions associated with depression. Resting-state functional magnetic resonance imaging and neurocognitive testing were conducted on the participants, and statistical package for the social sciences was utilized to analyze the behavioral data. Clinical and theoretical data were analyzed to evaluate acupuncture's effectiveness against gynecological cancer. In the research, there were 40 participants, 20 in each group. Except for psychomotor speed, there was no discernible difference in pre-chemotherapy cognitive test results between patients and healthy controls (HCs). However, there were substantial differences in post-treatment cognition test results, showing that the patient group had progressed. According to longitudinal graph analysis, the patient group's local and global brain efficiency significantly declined, and lower local efficiency was associated with lower raw Trail Making Test-A results. Furthermore, poorer verbal memory scores were associated with lower overall performance in the sick group but not in the HC group. According to the research, MDA has potential as a supplemental therapy since it may improve brain function and address depression-related neurological abnormalities in cancer patients. More research is required to fully comprehend the variations between cancer and depression-related brain areas during patient therapy, maybe incorporating MDA.

[Origin identification of Poria cocos based on hyperspectral imaging technology].

To realize the non-destructive and rapid origin discrimination of Poria cocos in batches, this study established the P. cocos origin recognition model based on hyperspectral imaging combined with machine learning. P. cocos samples from Anhui, Fujian, Guangxi, Hubei, Hunan, Henan and Yunnan were used as the research objects. Hyperspectral data were collected in the visible and near infrared band(V-band, 410-990 nm) and shortwave infrared band(S-band, 950-2 500 nm). The original spectral data were divided into S-band, V-band and full-band. With the original data(RD) of different bands, multiplicative scatter correction(MSC), standard normal variation(SNV), S-G smoothing(SGS), first derivative(FD), second derivative(SD) and other pretreatments were carried out. Then the data were classified according to three different types of producing areas: province, county and batch. The origin identification model was established by partial least squares discriminant analysis(PLS-DA) and linear support vector machine(LinearSVC). Finally, confusion matrix was employed to evaluate the optimal model, with F1 score as the evaluation standard. The results revealed that the origin identification model established by FD combined with LinearSVC had the highest prediction accuracy in full-band range classified by province, V-band range by county and full-band range by batch, which were 99.28%, 98.55% and 97.45%, respectively, and the overall F1 scores of these three models were 99.16%, 98.59% and 97.58%, respectively, indicating excellent performance of these models. Therefore, hyperspectral imaging combined with LinearSVC can realize the non-destructive, accurate and rapid identification of P. cocos from different producing areas in batches, which is conducive to the directional research and production of P. cocos.

Characteristics, differential diagnosis, individualized treatment, and prevention of hyperhomocysteinemia in newborns.

OBJECTIVES: This study aimed to investigate the incidence rate, clinical phenotype, gene variation spectrum, and prognosis of neonatal hyperhomocysteinemia (HHcy) and explore its diagnosis, individualised treatment, and prevention strategies. METHODS: We screened 84722 neonates for HHcy using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with biochemical detection, urine gas chromatography-mass spectrometry (GC-MS), and next-generation sequencing (NGS) for gene analysis to comprehensively differentiate and diagnose diseases. RESULTS: 18 children (P1-P18) were diagnosed with methylmalonic acidemia (MMA) and HHcy, and fourteen known and one new variant of the MMACHC gene were found. Five children showed poor mental reactions, brain dysplasia, lethargy, hyperbilirubinemia, and jaundice, whereas the other 13 children had no evident abnormalities. These children were all cobalamin- and folic acid-reactive types, and they were mainly supplemented with cobalamin, L-carnitine, betaine, and folic acid. The mother of P12 had a prenatal diagnosis at the next pregnancy; the results showed that MMACHC gene was not pathogenic and she gave birth to a healthy baby. One child (P19) was diagnosed with methylenetetrahydrofolate reductase (MTHFR) deficiency, and one new mutation was detected in the MTHFR gene. Patient P19 showed congenital brain dysplasia, neonatal anaemia, and hyperbilirubinemia, and treatment consisted mainly of betaine and cobalamin supplementation. One child (P20) was confirmed to have methionine adenosyltransferase I (MAT I) deficiency but had no clinical manifestations. After treatment, all the children had a good prognosis. CONCLUSION: The incidence of neonatal HHcy in the Zibo area was 1/4236, and the common pathogenic variants were c.609G>A, c.80A>G, and c.482G>A in the MMACHC gene. Patients with HHcy can achieve a good prognosis if pathogenic factors and targeted treatment are identified. Gene analysis and prenatal diagnosis contribute to the early prevention of HHcy.

Qiji Shujiang granules alleviates dopaminergic neuronal injury of parkinson's disease by inhibiting NLRP3/Caspase-1 pathway mediated pyroptosis.

BACKGROUND: The Qiji Shujiang granule (QJG) is a traditional Chinese drug widely used in treating PD patients. However, the potential mechanism of QJG in PD therapy is still unclear. PURPOSE: This study aims to examine the neuroprotective effects of QJG and the specific mechanism by which QJG alleviates MPTP/Probenecid-induced pyroptosis and offers an alternative for PD treatment. STUDY DESIGN AND METHODS: We first employed network pharmacology along with molecular docking to identify potential molecular targets and pathways. Subsequently, we validated our findings of RNA-sequencing (RNA-seq) analysis and experiments in vivo and vitro. Lentiviral systems and inhibitors were used for experiments. RESULTS: The protein-protein interactions (PPI) core genes network consists of NLRP3, CASP1 (caspase-1), TP53, and MAPK8. Pathway enrichment analysis revealed that inflammatory responses related to pyroptosis were significantly enriched. The molecular docking findings showed the highest degree of centrality regarding the top three bioactive compounds following the online database. RNA-seq analysis identified that NLRP3 inflammasome was significantly downregulated in the QJG group while it was significantly upregulated in the model group. Our findings revealed that QJG dose-dependently increased the total traveled distances, enhanced the dopaminergic neurons, and accelerated the restoration of the TH protein level, showing a good antioxidant capacity through increasing the SOD levels and decreasing MDA levels. QJG significantly reduced the expression levels of NLRP3, GSDMD-N, IL-1ß, and caspase-1 in striatum tissue. Furthermore, the group treated with OE-NLRP3 decreased cell viability, increased ROS and MDA levels, and promoted NLRP3, GSDMD-N, and caspase-1, in addition to IL-1ß expression levels. Furthermore, OE-NLRP3+QJG treatment significantly reversed the effect. In vivo experiments, QJG dose-dependently alleviated motor impairment by increasing the total traveled distances, rescued dopaminergic neurons, inhibited oxidative stress through increasing the SOD levels and decreasing MDA levels and suppressed NLRP3-mediated pyroptosis by reducing the expression levels of NLRP3, GSDMD-N, IL-1ß, and caspase-1 in MPTP induced PD Mice. Moreover, in vitro experiments, the OE-NLRP3 treated group decreased cell viability, increased ROS and MDA levels, and promoted NLRP3, GSDMD-N, caspase-1, in addition to IL-1ß expression levels. Furthermore, OE-NLRP3+QJG treatment significantly reversed the effect. CONCLUSIONS: This study provides pharmacological support for the use of QJG in the treatment of PD. Herein, we concluded that QJG induced the alleviation of pyroptosis by inhibiting the NLRP3/caspase-1 pathway to exert a neuroprotective effect.

[Lianmei Qiwu Decoction relieves diabetic cardiac autonomic neuropathy by regulating AMPK/TrkA/TRPM7 signaling pathway].

This study investigated the effect of Lianmei Qiwu Decoction(LMQWD) on the improvement of cardiac autonomic nerve remodeling in the diabetic rat model induced by the high-fat diet and explored the underlying mechanism of LMQWD through the AMP-activated protein kinase(AMPK)/tropomyosin receptor kinase A(TrkA)/transient receptor potential melastatin 7(TRPM7) signaling pathway. The diabetic rats were randomly divided into a model group, an LMQWD group, an AMPK agonist group, an unloaded TRPM7 adenovirus group(TRPM7-N), an overexpressed TRPM7 adenovirus group(TRPM7), an LMQWD + unloaded TRPM7 adenovirus group(LMQWD+TRPM7-N), an LMQWD + overexpressed TRPM7 adenovirus group(LMQWD+TRPM7), and a TRPM7 channel inhibitor group(TRPM7 inhibitor). After four weeks of treatment, programmed electrical stimulation(PES) was employed to detect the arrhythmia susceptibility of rats. The myocardial cell structure and myocardial tissue fibrosis of myocardial and ganglion samples in diabetic rats were observed by hematoxylin-eosin(HE) staining and Masson staining. The immunohistochemistry, immunofluorescence, real-time quantitative polymerase chain reaction(RT-PCR), and Western blot were adopted to detect the distribution and expression of TRPM7, tyrosine hydroxylase(TH), choline acetyltransferase(ChAT), growth associated protein-43(GAP-43), nerve growth factor(NGF), p-AMPK/AMPK, and other genes and related neural markers. The results showed that LMQWD could significantly reduce the arrhythmia susceptibility and the degree of fibrosis in myocardial tissues, decrease the levels of TH, ChAT, and GAP-43 in the myocardium and ganglion, increase NGF, inhibit the expression of TRPM7, and up-regulate p-AMPK/AMPK and p-TrkA/TrkA levels. This study indicated that LMQWD could attenuate cardiac autonomic nerve remodeling in the diabetic state, and its mechanism was associated with the activation of AMPK, further phosphorylation of TrkA, and inhibition of TRPM7 expression.

Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Patients with N2-3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin-fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin-gemcitabine with cisplatin-fluorouracil in N2-3 nasopharyngeal carcinoma. METHODS: We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18-65 years with untreated, non-keratinising, stage T1-4 N2-3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0-1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up. FINDINGS: From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36-52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin-fluorouracil group (n=120) or cisplatin-gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32-48). 3-year progression-free survival was 83·9% (95% CI 75·9-89·4; 19 disease progressions and 11 deaths) in the cisplatin-gemcitabine group and 71·5% (62·5-78·7; 34 disease progressions and seven deaths) in the cisplatin-fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32-0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin-gemcitabine group vs 34 [29%] of 116 in the cisplatin-fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin-gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin-fluorouracil group had treatment-related deaths. INTERPRETATION: Our findings suggest that concurrent adjuvant cisplatin-gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2-3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities.

Xue-Jie-San prevents the early development of colitis-associated intestinal fibrosis by blocking Notch1 and FGL1 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Xue-Jie-San (XJS), as a traditional Chinese herb prescription, has satisfactory effects on improving clinical symptoms and facilitating the healing of intestinal ulcers in patients with Crohn's disease (CD). This motivates the application of XJS on CD-associated complications. AIM OF THE STUDY: Intestinal fibrosis is a debilitating complication of CD. Currently, there is no effective medication available for preventing or reversing CD-related intestinal fibrosis. This study aimed to assess the efficacy and underlying mechanisms of XJS in the treatment of colitis-associated intestinal fibrosis. MATERIALS AND METHODS: A rat model of CD-related intestinal fibrosis was induced by 2,4,6-trinitrobenzene sulfonic acid administration and treated with XJS. The pathological changes of intestinal fibrosis were evaluated using Masson staining. Collagen deposition and epithelial-to-mesenchymal transition (EMT) were verified by immunohistochemical staining and Western blot analysis. Endothelial-to-mesenchymal transition (EndoMT) was assessed with immunofluorescence and immunohistochemical staining as well as Western blot analysis. Transmission electron microscopy was utilized to observe autophagosomes. The levels of autophagy-related proteins were detected via immunofluorescence staining and Western blot. Finally, the mTOR/ULK1 signaling pathway regulated by Notch1 or FGL1 was analyzed by Western blot. RESULTS: The results found that XJS ameliorated intestinal fibrosis through reducing the deposition of collagens such as Collagen 1 and Collagen 3. XJS inhibited the EMT process by increasing E-cadherin levels and decreasing the expressions of N-cadherin, Vimentin and Snail, which played a crucial role in collagen secretion and intestinal fibrosis. In addition, XJS also repressed the EndoMT process as reflected by the upregulation of CD31 and VE-cadherin levels and the downregulation of FSP1 and α-SMA expressions. Autophagy was activated following XJS treatment via suppression of the mTOR/ULK1 signaling pathway. Furthermore, XJS acted as an inhibitor of Notch1 and FGL1 signals, both of which regulated the mTOR signaling. CONCLUSIONS: Our findings validated that XJS prevented the early development of CD-related intestinal fibrosis by blocking the Notch1 and FGL1 signaling pathways to activate autophagy and thereby inhibit EMT and EndoMT.

Gallic acid ameliorates dextran sulfate sodium-induced ulcerative colitis in mice via inhibiting NLRP3 inflammasome.

Background: Ulcerative colitis (UC) is a chronic recurrent inflammatory bowel disease (IBD). The conventional drugs for UC may induce severe side effects. Herbal medicine is considered as a complementary and alternative choice for UC. Purpose: This study aims to estimate the effect of natural polyphenol gallic acid (GA) on the NLRP3 inflammasome with dextran sulfate sodium (DSS)-induced colitis in mice. Study design: The body weights and symptoms of BALB/c mice were recorded. Histological evaluation, ELISA, q-PCR, immunohistochemistry, and western blotting were carried out to observe the morphology, cytokine contents, mRNA expressions, and protein expressions, respectively. Lipopolysaccharide (LPS)-induced RAW264.7 macrophage was used to probe GA's effect on relative protein expression. Results: GA attenuated weight loss (p < 0.05), relieved symptoms, and ameliorated colonic morphological injury (p < 0.05) in mice with colitis induced by DSS. GA also lowered the contents of TNF-α, IL-1ß, IL-18, IL-33, and IFN-γ in the serum and colon of mice, which were elevated by DSS, downregulated protein, and mRNA expressions of the NLRP3 pathway in the colon tissue. Furthermore, GA downregulated the expressions of NLRP3 (p < 0.05), iNOS (p < 0.01), COX2 (p < 0.01), and P-p65 (p < 0.05), and suppressed NO release (p < 0.001) in LPS-induced RAW264.7 cells. Conclusion: GA ameliorated DSS-induced UC in mice via inhibiting the NLRP3 inflammasome. These findings furnish evidence for the anti-inflammatory effect of herbal medicines containing GA on UC.

Yin-chen Wu-ling powder alleviate cholestatic liver disease: Network pharmacological analysis and experimental validation.

BACKGROUND: Yin-chen Wu-ling Powder (YWP) has potential therapeutic effects on cholestatic liver disease (CLD), however, its active compounds and conceivable mechanism are as yet indistinct. METHODS: The network pharmacology and gene function annotation examined the multiple active ingredients, potential targets, and possible mechanisms of YWP in CLD treatment. Then the molecular docking reassured the reliability of the core compounds including the key genes and farnesoid X receptor (FXR). Finally, The Mdr2-/- mice were used to test the effect and mechanism of YWP against CLD. RESULTS: The network analysis identified nine main active ingredients, including quercetin, capillarisin, eupalitin, isorhamnetin, skrofulein, genkwanin, cerevisterol, gederagenin, and sitosterol. The PPI network predicted the ten hub genes involved were AKT1, MAPK1, MAPK14, IL6, RXRA, ESR1, IL10, NCOA1, CAV1, and EGFR. The KEGG and GO analysis showed that YWP might contribute to CLD treatment through the PI3K/Akt and MAKP signalings to manage pathological reactions, for instance, inflammatory responses. The molecular docking displayed a functional similarity among the core compounds with ursodeoxycholic acid (UDCA) and Obeticholic acid (OCA) on the effects on AKT1, MAPK1, MAPK14, RXRA, and ESR, and the affinity to FXR. In addition, the YWP could significantly attenuate hepatic injury and improve inflammatory response in Mdr2-/- mice. The mechanism exploration showed that YWP mainly decreased inflammatory response by inhibiting AKT/P38MAPK signaling. CONCLUSION: This study firstly revealed the multiple active ingredients, potential targets, and possible mechanism of YWP to treat CLD based on network pharmacology Analysis and molecular docking. YWP could alleviate cholestasis in Mdr2-/- mice by impairing inflammation via inhibiting AKT/P38MAPK Signaling.

Hierarchical deployment of Tbx3 dictates the identity of hypothalamic KNDy neurons to control puberty onset.

The neuroendocrine system consists of a heterogeneous collection of neuropeptidergic neurons in the brain, among which hypothalamic KNDy neurons represent an indispensable cell subtype controlling puberty onset. Although neural progenitors and neuronal precursors along the cell lineage hierarchy adopt a cascade diversification strategy to generate hypothalamic neuronal heterogeneity, the cellular logic operating within the lineage to specify a subtype of neuroendocrine neurons remains unclear. As human genetic studies have recently established a link between TBX3 mutations and delayed puberty onset, we systematically studied Tbx3-derived neuronal lineage and Tbx3-dependent neuronal specification and found that Tbx3 hierarchically established and maintained the identity of KNDy neurons for triggering puberty. Apart from the well-established lineage-dependent fate determination, we uncovered rules of interlineage interaction and intralineage retention operating through neuronal differentiation in the absence of Tbx3. Moreover, we revealed that human TBX3 mutations disturbed the phase separation of encoded proteins and impaired transcriptional regulation of key neuropeptides, providing a pathological mechanism underlying TBX3-associated puberty disorders.

[Responses of soil microbial carbon use efficiency to short-term nitrogen addition in Castanopsis fabri forest]. / ç½—æµ®æ ²æž—åœŸå£¤å¾®ç”Ÿç‰©ç¢³åˆ©ç”¨æ•ˆçŽ‡å¯¹çŸ­æœŸæ°®æ·»åŠ çš„å“åº”.

As an important parameter regulating soil carbon mineralization, microbial carbon use efficiency (CUE) is essential for the understanding of carbon (C) cycle in terrestrial ecosystems. Three nitrogen supplemental levels, including control (0 kg N·hm-2·a-1), low nitrogen (40 kg N·hm-2·a-1), and high nitrogen (80 kg N·hm-2·a-1), were set up in a Castanopsis fabri forest in the Daiyun Mountain. The basic physical and chemical properties, organic carbon fractions, microbial biomass, and enzyme activities of the soil surface layer (0-10 cm) were measured. To examine the effects of increasing N deposition on microbial CUE and its influencing factors, soil microbial CUE was measured by the 18O-labelled-water approach. The results showed that short-term N addition significantly reduced microbial respiration rate and the activities of C and N acquisition enzymes, but significantly increased soil microbial CUE. ß-N-acetyl amino acid glucosidase (NAG)/microbial biomass carbon (MBC), microbial respiration rate, ß-glucosidase (BG)/MBC, cellulose hydrolase (CBH)/MBC, and soil organic carbon content were the main factors affecting CUE. Moreover, CUE significantly and negatively correlated with NAG/MBC, microbial respiration rate, BG/MBC, and CBH/MBC, but significantly and positively correlated with soil organic carbon. In summary, short-term N addition reduced the cost of soil microbial acquisition of C and N and microbial respiration, and thus increased soil microbial CUE, which would increase soil carbon sequestration potential of the C. fabri forest.

Cardioprotective Mechanism and Active Compounds of Folium Ginkgo on Adriamycin-Induced Cardiotoxicity: A Network Pharmacology Study.

Objective: To investigate the mechanism of Folium Ginkgo (FG) against adriamycin-induced cardiotoxicity (AIC) through a network pharmacology approach. Methods: Active ingredients of FG were screened by TCMSP, and the targets of active ingredient were collected by Genclip3 and HERB databases. AIC-related target genes were predicted by Genecards, OMIM, and CTD databases. Protein-protein interaction (PPI) network was constructed by STRING platform and imported into Cytoscape software to construct the FG-active ingredients-targets-AIC network, and CytoNCA plug-in was used to analyze and identify the core target genes. The Metascape platform was used for transcription factor, GO and signaling pathway enrichment analysis. Results: 27 active ingredients of FG and 1846 potential targets were obtained and 358 AIC target genes were retrieved. The intersection of FG and AIC targets resulted in 218 target genes involved in FG action. The top 5 active ingredients with most targets were quercetin, luteolin, kaempferol, isorhamnetin, and sesamin. After constructing the FG-active ingredients-targets-AIC network, CytoNCA analysis yielded 51 core targets, of which the top ranked target was STAT3. Ninety important transcription factors were enriched by transcription factor enrichment analysis, including RELA, TP53, NFKB1, SP1, JUN, STAT3, etc. The results of GO enrichment analysis showed that the effective active ingredient targets of FG were involved in apoptotic signaling, response to growth factor, cellular response to chemical stress, reactive oxygen species metabolic process, etc. The signaling pathway enrichment analysis showed that there were many signaling pathways involved in AIC, mainly including pathways in cancer, FOXO signaling pathway, AGE-RAGE signaling pathway in diabetic complications, signaling by interleukins, and PI3K-AKT signaling pathway,. Conclusions: The study based on a network pharmacology approach demonstrates that the possible mechanisms of FG against AIC are the involvement of multicomponents, multitargets, and multipathways, and STAT3 may be a key target. Further experiments are needed to verify the results.

Thermal Control Using Far-Infrared Irradiation for Producing Deglycosylated Bioactive Compounds from Korean Ginseng Leaves.

Although ginseng leaf is a good source of health-beneficial phytochemicals, such as polyphenols and ginsenosides, few studies have focused on the variation in compounds and bioactivities during leaf thermal processing. The efficiency of far-infrared irradiation (FIR) between 160 °C and 200 °C on the deglycosylation of bioactive compounds in ginseng leaves was analyzed. FIR treatment significantly increased the total polyphenol content (TPC) and kaempferol production from panasenoside conversion. The highest content or conversion ratio was observed at 180 °C (FIR-180). Major ginsenoside contents gradually decreased as the FIR temperature increased, while minor ginsenoside contents significantly increased. FIR exhibited high efficiency to produce dehydrated minor ginsenosides, of which F4, Rg6, Rh4, Rk3, Rk1, and Rg5 increased to their highest levels at FIR-190, by 278-, 149-, 176-, 275-, 64-, and 81-fold, respectively. Moreover, significantly increased antioxidant activities were also observed in FIR-treated leaves, particularly FIR-180, mainly due to the breakage of phenolic polymers to release antioxidants. These results suggest that FIR treatment is a rapid and efficient processing method for producing various health-beneficial bioactive compounds from ginseng leaves. After 30 min of treatment without leaf burning, FIR-190 was the optimum temperature for producing minor ginsenosides, whereas FIR-180 was the optimum temperature for producing polyphenols and kaempferol. In addition, the results suggested that the antioxidant benefits of ginseng leaves are mainly due to polyphenols rather than ginsenosides.

Botany, traditional uses, phytochemistry, pharmacological and toxicological effects of Croton tiglium Linn.: a comprehensive review.

OBJECTIVES: Croton tiglium Linn. (Euphorbiaceae) is an ancient medicinal plant that has been used for a long time, which is widely distributed in tropical and subtropical regions. And it is widely used for defecation, induced labour, treatment of gastrointestinal diseases, headache, as well as rheumatoid arthritis. KEY FINDINGS: Approximately 150 compounds have been isolated and identified from the seeds, stems, leaves and branches of C. tiglium, including fatty acids, terpenoids, alkaloids, the plants proteins and other types of components. Based on a wide range of biological properties, C. tiglium has a wide range of pharmacological effects, such as antitumor, anti-HIV, analgesic, anti-inflammatory and antibacterial effects. SUMMARY: The review aims to provide a critical and comprehensive evaluation of the botany, phytochemistry, pharmacology and toxicity of C. tiglium, with a vision for promoting further pharmaceutical research to explore its complete potential for better clinical application. The tigliane diterpenoids have been the most studied compounds isolated from C. tiglium, which showing a variety of biological activities, but there is insufficient evidence to explain the mechanism of action. In addition, C. tiglium may have potential toxic effects, and it is necessary to reduce the toxic effects to ensure the safety of clinical medication, which may promote the discovery and development of new drugs.

Phytochemicals in traditional Chinese medicine can treat gout by regulating intestinal flora through inactivating NLRP3 and inhibiting XOD activity.

OBJECTIVES: Gout is a common disease caused by hyperglycemia. Traditional drugs for gout have both good therapeutic effects and serious side effects. Traditional Chinese medicine (TCM) is one of the potential sources of modern medicine, and is the development of new drugs for many diseases, including gout. TCM is an indispensable part of gout treatment. Compared with anti-gout medication commonly used in clinic (e.g. the xanthine oxidase inhibitors allopurinol and febuxostat), traditional Chinese medicine has fewer side effects in the treatment of gout and can safely control serum uric acid and the level of inflammation. However, there have been few studies on how traditional Chinese medicine controls uric acid and inflammation levels in patients with gout. KEY FINDINGS: Herbs are a valuable resource in the search for new drugs to treat many diseases, including gout. Phytochemicals in TCM treatment of gout mainly includes two aspects, anti-inflammatory and reducing uric acid content. The anti-inflammatory mechanism is mainly through the inactivation of NF-κB and NLRP3 inflammasome to reduce the inflammatory response induced by uric acid crystals. The mechanism of lowering uric acid is mainly through inhibiting the activity of xanthine oxidase and up-regulating the expression of URAT1 and GLUT9.In recent years, the intestinal flora has become a new field of understanding diseases. It has been observed that the occurrence of gout is closely related to changes in the intestinal flora. Herbaceous plants contain fiber, polyphenols, polysaccharides and other active components. When taken orally, Chinese herbs act like prebiotics. After traditional Chinese medicine treatment, the abundance levels of Bifidobacterium, Lactobacillus, Bacteroidetes and Prevotella were increased, while the abundance of Proteus and the Firmicutes/Bacteroidetes ratio were decreased. Changes in the intestinal flora led to further changes in its metabolites, including short-chain fatty acids (SCFAs) and lipopolysaccharide (LPS), which ultimately down-regulate the TLR4/NF-κB inflammatory signaling pathway, up-regulate GLUT9 and URAT1 gene expression and inhibition of xanthine oxidase activity. Destruction of the intestinal barrier is also an important factor in the occurrence of gout. Disruption of the intestinal barrier allows LPS to enter the bloodstream and activates the expression of various inflammatory factors, which causes gout.

Bushen Jianpi Formula Combined with Entecavir for the Treatment of HBeAg-Negative Chronic Hepatitis B: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Bushen Jianpi formula (BSJPF, also known as Lingmao formula) is a traditional Chinese medicine for chronic hepatitis B (CHB). The previous study has suggested that the treatment combination of BSJPF and entecavir (ETV) can achieve a significant loss of hepatitis B e antigen (HBeAg) and a significant decrease in serum level of hepatitis B virus (HBV) DNA in HBeAg-positive CHB patients with mildly elevated alanine aminotransferase. Objective: This study aimed to evaluate the efficacy and safety of BSJPF combined with ETV for treating HBeAg-negative CHB patients. Methods: A total of 640 patients were assigned randomly to the treatment group (receiving BSJPF combined with ETV for 96 weeks) or the control group (receiving a placebo combined with ETV for 96 weeks) in a 1 : 1 ratio. The primary endpoints are the rate of loss of hepatitis B surface antigen (HBsAg). The secondary outcomes included the rate of decrease in the HBsAg concentration to ≥1 lg·IU/mL, the HBV DNA suppression, the decline of the level of covalently closed circular DNA (cccDNA) in the liver, histological improvements, and the rate of ALT normalization. Results: The rate of HBsAg loss in the treatment group was significantly higher than that of the control group (5.5% versus 1.8%, P=0.031). There were 11.1% of patients in the treatment group who recorded a reduction in HBsAg ≥1 lg·IU/mL, which is better than 5.9% of patients in the control group (P=0.043). There was no significant difference between the two groups with regard to the rate of HBV DNA clearance, the reduction in intrahepatic cccDNA, and the rate of ALT normalization (P > 0.05). The rate of liver fibrosis improvement in the treatment group was better than that of the control group (35.5% versus 11.8%, P=0.031), but there was no difference in necroinflammatory improvement (P > 0.05). The adverse events (AEs) were similar between the two groups, except for the abnormal kidney function, with 2.2% in the control group and 0.0% in the treatment group (P=0.028). Conclusion: The combination of BSJPF and ETV can increase the rate of HBsAg loss and the rate of histological fibrosis improvement without serious adverse events in CHB patients. Trial Registration. This trial is registered with ChiCTR-IOR-16009880 on November 16, 2016-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=16836.

Buffering culture solution significantly improves astaxanthin production efficiency of mixotrophic Haematococcus pluvialis.

Sodium acetate (NaAc) supplementation, often used to increase the growth of H. pluvialis under low light, but promotes cell death under high light; its underlying reasons and solutions are rarely reported. Here, NaAc supplementation was found to rapidly increase pondus hydrogenii (pH) of culture solution, elevate reactive oxygen species (ROS), and cause cell death immediately under higher light. Adjusting pH of NaAc supplemented culture solution with 10 mM Tris-HCl once before high light significantly reduced cell mortality and increased astaxanthin yield. When verified in a 5-litre photobioreactor, this novel method produced over 4.0% of dry weight (DW) astaxanthin within only 8-10 days. In summary, this study explained reasons underlying NaAc supplementation-induced cell death and provided an rapid, easy and effective method to produce high amount of astaxanthin in H. pluvialis.

Therapeutic Targets of Bufalin on Renal Carcinoma and Mechanisms: Experimental Validation of Network Pharmacology Analysis.

The possible targets underlying the activity of bufalin on renal cell carcinoma (RCC) were investigated using network pharmacology and experimental approaches. PharmMapper and other databases were explored for predicting the bufalin targets and RCC-related targets. Finally, the enriched pathways and the targets were analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. Furthermore, in vitro cell experiments were used to verify bufalin activation of AKT and MAPK signaling pathways in human mesangial cells. The therapeutic targets related to bufalin were identified via 35 intersecting targets. GO analysis identified 29 molecular functions, 16 cellular components, and 91 biological processes. KEGG pathway annotation identified 15 signal transduction pathways and 4 tumor-related pathways.