The new era of lung cancer therapy: Combining immunotherapy with ferroptosis.

Ferroptosis is an unconventional programmed cell death mode caused by phospholipid peroxidation dependent on iron. Emerging immunotherapies (especially immune checkpoint inhibitors) have the potential to enhance lung cancer patients' long-term survival. Although immunotherapy has yielded significant positive applications in some patients, there are still many mechanisms that can cause lung cancer cells to evade immunity, thus leading to the failure of targeted therapies. Immune-tolerant cancer cells are insensitive to conventional death pathways such as apoptosis and necrosis, whereas mesenchymal and metastasis-prone cancer cells are particularly vulnerable to ferroptosis, which plays a vital role in mediating immune tolerance resistance by tumors and immune cells. As a result, triggering lung cancer cell ferroptosis holds significant therapeutic potential for drug-resistant malignancies. Here, we summarize the mechanisms underlying the suppression of ferroptosis in lung cancer, highlight its function in the lung cancer immune microenvironment, and propose possible therapeutic strategies.

Quality Evaluation of Shexiang Tongxin Dropping Pill Based on HPLC Fingerprints Combined with HPLC-Q-TOF-MS/MS Method.

Shexiang Tongxin Dropping Pill (STP) is a composite formula of traditional Chinese medicine that is widely used for the treatment of cardiovascular diseases. It consists of seven medicinal extracts thereof or materials, including Bufonis venenum, synthetic Moschus, Panax ginseng, Bovis calculus artifactus, Bear bile powder, Salvia miltiorrhiza Bge and synthetic borneol. However, it is considerably difficult to evaluate the quality of STP due to its complex chemical compositions. This paper was designed to explore a comprehensive and systematic method combining fingerprints and chemical identification for quality assessment of STP samples. Twenty batches of STP samples were analyzed by high-performance liquid chromatography (HPLC) and high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Ten common peaks were detected by HPLC fingerprint similarity evaluation system. Meanwhile, 100 compounds belonging to 4 structural characteristics, including 23 bufadienolides, 36 organic acids, 34 saponins and 7 other types, were systematically identified as the basic components in STP. This study could be used for clarifying the multiple bioactive substances and developing a comprehensive quality evaluation method of STP.

Minimally Invasive Delivery of Percutaneous Ablation Agent via Magnetic Colloidal Hydrogel Injection for Treatment of Hepatocellular Carcinoma.

Percutaneous thermotherapy, a minimally invasive operational procedure, is employed in the ablation of deep tumor lesions by means of target-delivering heat. Conventional thermal ablation methods, such as radiofrequency or microwave ablation, to a certain extent, are subjected to extended ablation time as well as biosafety risks of unwanted overheating. Given its effectiveness and safety, percutaneous thermotherapy gains a fresh perspective, thanks to magnetic hyperthermia. In this respect, an injectable- and magnetic-hydrogel-construct-based thermal ablation agent is likely to be a candidate for the aforementioned clinical translation. Adopting a simple and environment-friendly strategy, a magnetic colloidal hydrogel injection is introduced by a binary system comprising super-paramagnetic Fe3O4 nanoparticles and gelatin nanoparticles. The colloidal hydrogel constructs, unlike conventional bulk hydrogel, can be easily extruded through a percutaneous needle and then self-heal in a reversible manner owing to the unique electrostatic cross-linking. The introduction of magnetic building blocks is exhibited with a rapid magnetothermal response to an alternating magnetic field. Such hydrogel injection is capable of generating heat without limitation of deep penetration. The materials achieve outstanding therapeutic results in mouse and rabbit models. These findings constitute a new class of locoregional interventional thermal therapies with minimal collateral damages.

The effect and mechanism of novel methoxy curcumin analogs based on network pharmacology.

In this study, a series of novel compounds were synthesized by introducing the 3,4,5-trimethoxyphenyl and isatin groups into the monocarbonyl skeleton of curcumin. The possible biological activities and potential targets for these compounds were explored through network pharmacology. The results revealed that these compounds could significantly inhibit production of the inflammatory factors IL-6 and TNF-α, and suppress phosphorylation of the extracellular signal-regulated kinase (ERK) protein. Moreover, molecular docking experiments showed that the ERK protein was the potential target for these compounds. In summary, this study, through network pharmacology, presents a novel series of methoxy curcumin analogs as potent anti-inflammatory drugs.

Free total rhubarb anthraquinones protect intestinal mucosal barrier of SAP rats via inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is the peeled and dried roots of Rheum palmatum L. and Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) were isolated and extracted from rhubarb. Previous studies have revealed that the early administration of FTRAs protects the intestinal mucosal barrier in rats with severe acute pancreatitis (SAP), the mechanism of which is not yet clear. However, we observed an enhanced expression of intestinal pyroptotic factors in rats treated with SAP, which may be related to the mechanism of intestinal barrier protection by FTRAs. AIM OF THE STUDY: The main objective of this study was to investigate the mechanism by which FTRAs protect the intestinal mucosal barrier in SAP rats, focusing on the classical pyroptosis pathway. MATERIALS AND METHODS: SAP was induced in rats through retrograde injection of sodium taurocholate via the pancreaticobiliary duct. Subsequently, FTRAs (22.5, 45, and 90 mg/kg), rhubarb (900 mg/kg, positive control), and saline (control) were administered at 0 h (immediately), 12 h, and 24 h post-surgery. Pancreatic and intestinal tissue injury, positive PI staining rate, and expression levels of various factors in intestinal tissues were compared across different groups. These factors include diamine oxidase (DAO), lactate dehydrogenase (LDH), high mobility group box chromosomal protein 1(HMGB1) and pro-inflammatory factors in intestinal and serum, pyroptosis-associated factors, toll-like receptor 4 (TLR-4), nuclear factor kappa-B (NF-kB), apoptosis-associated speck-like protein (ASC), NOD-like receptor protein 3 (NLRP3), cysteine protease-1 (caspase-1) and Gasdermin (GSDMD). RESULTS: The findings indicated that FTRAs protected the damaged intestine and pancreas and restored the expression of intestinal epithelial junction proteins in SAP rats. Additionally, it reduced intestinal and serum levels of DAO, interleukin 1, interleukin 18, HMGB1, and LDH, attenuated intestinal Positive PI staining rate, and significantly decreased the expressions of TLR-4, NF-kB, ASC, NLRP3, caspase-1 and GSDMD in SAP rats. CONCLUSIONS: The results suggest that FTRAs inhibited pyroptosis through down-regulation of the NLRP3-Caspase-1-GSDMD and TLR-4- NF-kB signaling pathways of intestinal tissues., thereby protecting the intestinal barrier of SAP rats.

[Liver targeting of compound liposomes mediated by glycyrrhetinic acid derivative receptor and its effect on hepatic stellate cells].

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) µg·h·mL~(-1) to(550.39±12.34) µg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) µg·h·mL~(-1) to(0.65±0.04) µg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) µg·h·mL~(-1) to(96.21±3.75) µg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.

Experiences and requirements in nutritional management of patients with esophageal cancer: a systematic review and qualitative meta-synthesis.

PURPOSE: Nutritional management of patients with esophageal cancer is a significant issue. This systematic review aimed to comprehensively synthesize qualitative research evidence on the experiences and requirements in nutritional management from the perspective of patients with esophageal cancer. METHODS: A systematic review and meta-synthesis of qualitative studies were conducted. Studies written in Chinese or English were retrieved from nine databases, namely, PubMed, Web of Science, Cochrane Library, CINAHL, Embase, CNKI, WanFang, VIP, and SinoMed, from inception to December 23, 2022. After screening the titles, abstracts, and full texts, 19 articles were finally included for quality assessment and meta-synthesis. RESULTS: Three comprehensive themes were derived. These were dietary experiences (perception of symptoms and dietary behaviors), emotional experiences (negative and positive emotions), and social support (inappropriate social support and inadequate nutritional management). CONCLUSIONS: The experiences and requirements of esophageal cancer patients in terms of nutritional management during treatment and rehabilitation were reviewed and factors influencing nutritional management were discussed. The findings suggested that medical institutions should expedite the development of comprehensive nutritional management systems, create conducive nutritional environmental facilities, and establish interdisciplinary teams to implement personalized comprehensive interventional models for the management of patient nutrition. These steps would maximize the effectiveness of nutritional therapy, promote early patient recovery, and bridge the gap between healthcare professionals and patients in the understanding of nutritional management.

Optimal timing of free total rhubarb anthraquinones on immune regulation in rats with severe acute pancreatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is the peeled and dried root of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of anti-inflammation and immunological modulation. The timing of immune regulation is a major problem in the immunotherapy for severe acute pancreatitis (SAP). several studies reported that FTRAs could reduce systemic inflammatory responses by inhibiting early immune overactivity in the gut in rats with SAP. But, the optimal timing of rhubarb and FTRAs administration is not clear in clinical practice. Therefore, the time window for the best efficacy of rhubarb and FTRAs in the treatment of SAP patients should be further elucidated. AIM OF THE STUDY: The main purpose of the present study was to evaluate the efficacy and optimal timing of immune modulation with FTRAs in the treatment of SAP in rats. MATERIALS AND METHODS: FTRAs (22.5, 45 and 90 mg/kg), Rhubarb (RHU) (900 mg/kg, positive control) or normal saline (vehicle control) were initiated at 0 (immediately), 48 and 72 h every 12 h for three times in total. The therapeutic effects of FTRAs and RHU on pancreas and intestinal tissues injury, secondary infection with pseudomonas aeruginosa (PA), amylase, lipase, D-lactic acid (DLA), endotoxin (ET), proinflammatory and anti-inflammatory cytokines, macrophages, dendritic cells and regulatory T cells (Tregs) in the blood, small intestine and/or mesenteric lymph node (MLN) were determined in rats with SAP after treatment. RESULTS: The results showed that administration of FTRAs at 0 h was superior to 48 h and 72 h, which significantly protected the injury of pancreas and intestinal tissues, reduced the mortality induced by secondary infection with PA, decreased the levels of amylase, lipase, DLA, ET, tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), IL-6, IL-8, IL-18 and Tregs, and increased the levels of IL-4, sTNF-αR, macrophages and dendritic cells, secretary immunoglobulin A (SIgA) in the blood and/or small intestinal tissues in rats with SAP. CONCLUSIONS: In conclusion, our studies indicate that the treatment window of FTRAs for SAP is within 48 h of development, administration of FTRAs at the early stage (0 h, immune overreaction period) was the optimal time and superior to that of 48 h and 72 h for its therapeutic efficacy. The earlier the administration of FTRAs, the better the therapeutic efficacy. Therefore, our data may provide a scientific rationale for the clinical application and optimal timing of FTRAs in the treatment of SAP.

Self-assembling ferrimagnetic fluorescent micelles for bioimaging guided efficient magnetic hyperthermia therapy.

Multifunctional magnet-fluorescent nanocomposites are widely applied in biomedical applications. Incorporating biocompatible quantum dots with highly ferrimagnetic magnetic nanoparticles into one nanoplatform for achieving efficient magnetic hyperthermia therapy (MHT) is very important. Herein, we reported an amphiphilic block copolymer with a flowable hydrophobic chain to encapsulate highly ferrimagnetic magnetic nanoparticles and ZnS/InP quantum dots via a facile self-assembly method. The obtained ferrimagnetic fluorescent micelle (FMFM) exhibited a uniform diameter of about 180 nm. In stark contrast, larger aggregation (400 nm in diameter) inevitably occurred using common poly(D,L-lactide) (PLA)-based amphiphilic block copolymer with a rigid hydrophobic chain, which was readily cleared by the reticuloendothelial system (RES). The flowable FMFM exhibited long-term colloidal stability within one month and desired fluorescent stability within 84 h. Benefiting from the high ferrimagnetism, the FMFM revealed excellent magnetic heating effect and magnetic resonance imaging capability. With accurate manipulation under an external magnetic field, FMFM realized in vitro enhanced fluorescence imaging sensitivity and accumulation efficiency at the tumor region, achieving in vitro and vivo improved MHT efficacy.

The synergistic compatibility mechanisms of fuzi against chronic heart failure in animals: A systematic review and meta-analysis.

Background: Fuzi's compatibilities with other medicines are effective treatments for chronic heart failure. Pre-clinical animal experiments have indicated many possible synergistic compatibility mechanisms of it, but the results were not reliable and reproducible enough. Therefore, we performed this systematic review and meta-analysis of pre-clinical animal studies to integrate evidence, conducted both qualitative and quantitative evaluations of the compatibility and summarized potential synergistic mechanisms. Method: An exhaustive search was conducted for potentially relevant studies in nine online databases. The selection criteria were based on the Participants, Interventions, Control, Outcomes, and Study designs strategy. The SYRCLE risk of bias tool for animal trials was used to perform the methodological quality assessment. RevMan V.5.3 and STATA/SE 15.1 were used to perform the meta-analysis following the Cochrane Handbook for Systematic Reviews of Interventions. Result: 24 studies were included in the systematic review and meta-analysis. 12 outcomes were evaluated in the meta-analysis, including BNP, HR, HWI, ALD, LVEDP, LVSP, EF, FS, +dP/dtmax, -dP/dtmax, TNF-α and the activity of Na + -K + -ATPase. Subgroup analyses were performed depending on the modeling methods and duration. Conclusion: The synergistic Fuzi compatibility therapeutic effects against CHF animals were superior to those of Fuzi alone, as shown by improvements in cardiac function, resistance to ventricular remodeling and cardiac damage, regulation of myocardial energy metabolism disorder and RAAS, alleviation of inflammation, the metabolic process in vivo, and inhibition of cardiomyocyte apoptosis. Variations in CHF modeling methods and medication duration brought out possible model-effect and time-effect relationships.

Melatonin Rescues Dimethoate Exposure-Induced Meiotic and Developmental Defects of Porcine Oocytes.

Dimethoate (DT) is an environmental pollutant widely used in agricultural fields and home gardens. Studies have shown that exposure to DT causes reproductive defects in both male and female animals. However, the effects of DT exposure on oocyte maturation and the approach to counteract it are not yet known. Here, we investigated the toxicity of DT on porcine oocyte maturation and the protective effects of melatonin (MT) on DT-exposed oocytes. DT exposure with 1.5 mM partially inhibited cumulus cell expansion and significantly reduced the rate of first polar body extrusion (pb1) during oocyte maturation. Parthenogenetically activated embryos derived from DT-exposed oocytes could not develop to the 2-cell and blastocyst stage. Furthermore, DT exposure led to a significant increase in the rates of misaligned chromosomes, disorganized spindles, and abnormal actin assembly. DT exposure severely disrupted the distribution patterns of mitochondria in oocytes but did not change the subcellular localizations of cortical granules. Importantly, MT supplementation rescued the meiotic and developmental defects of DT-exposed oocytes through repressing the generation of excessive reactive oxygen species (ROS) and autophagy, and DNA damage accumulation. These results demonstrate that melatonin protects against meiotic defects induced by DT during porcine oocyte maturation.

Stabilization and mechanism of uranium sequestration by a mixed culture consortia of sulfate-reducing and phosphate-solubilizing bacteria.

In this study, a highly efficient phosphate-solubilizing bacteria (PSB) (Pantoea sp. grinm-12) was screened out from uranium (U) tailings, and the carbon and nitrogen sources of mixed culture with sulfate-reducing bacteria (SRB) were optimized. Results showed that the functional expression of SRB-PSB could be promoted effectively when glucose + sodium lactate was used as carbon source and ammonium nitrate + ammonium sulfate as nitrogen source. The concentration of PO43- in the culture system could reach 107.27 mg·L-1, and the sulfate reduction rate was 81.72%. In the process of biological stabilization of U tailings by mixed SRB-PSB culture system, the chemical form of U in the remediation group was found to transfer to stable state with the extension of remediation time, which revealed the effectiveness of bioremediation on the harmless treatment of U tailings. XRD, FT-IR, SEM-EDS, high-throughput sequencing, and metagenomics were also used to assist in revealing the microstructure and composition changes during the biological stabilization process, and explore the microbial community/functional gene response. Finally, the stabilization mechanism of U was proposed. In conclusion, the stabilization of U in U tailings was realized through the synergistic effect of bio-reduction, bio-precipitation, and bio-adsorption.

Effects and molecular mechanisms of Achyranthes bidentata polypeptide k on proliferation of Schwann cells.

BACKGROUND: Achyranthes bidentata polypeptide k (ABPPk) is an active ingredient separated from the Achyranthes bidentata polypeptides (ABPP) in traditional Chinese medicine. In the present study, we investigated the promoting effects and molecular mechanisms of ABPPk on the proliferation of Schwann cells (SCs). METHODS: Primary SCs were cultured with ABPPk or nerve growth factor (NGF) in vitro, and cell viability, cell cycle, EdU assay, and the expressions of proliferating cell nuclear antigen (PCNA) and Ki67 were analyzed. In addition, RNA-seq was used for bioinformatics analysis at different time points. PCNA was detected at different time points in a rat sciatic nerve injury model to further determining the role of ABPPk in sciatic nerve injury repair. RESULTS: We found that ABPPk could effectively promote the proliferation of SCs, while ABPPk and NGF had different molecular mechanisms for their proliferation at different time points. Weighted gene co-expression network analysis (WGCNA) showed that ABPPk was mainly involved in the positive regulation of cell proliferation and epigenetic regulation of cell proliferation, while the main cell proliferation-related modules that NGF participated in were attenuation of negative regulation of cell proliferation and positive regulation of cell cycle. There were significant differences in the genes involved in different modules between the two groups, and ABPPk differed from NGF in the biological process of SC migration, differentiation, movement, and development in terms of action time and key genes. Functional enrichment analysis revealed ABPPk had more advantages and participation in the axon extension and vascular system areas. Furthermore, ABPPk significantly promoted the proliferation of SCs in vivo. CONCLUSIONS: Through in vitro and in vivo studies, we identified the promoting effects of ABPPk on the proliferation of SCs. Using high-throughput sequencing technology, our work more comprehensively revealed the characteristics and mechanism of ABPPk on SCs. These results further enrich an understanding of the positive function and molecular mechanism of ABPPk in peripheral nerve regeneration and are conducive to the discovery of new therapeutic targets for peripheral nerve regeneration.

A tag based joint extraction model for Chinese medical text.

Information extraction in medical field is an important method to structure medical knowledge and discover new knowledge. Traditional methods handle this task in a pipelined manner regarding the entity recognition and relation extraction as two sub-tasks, which, however, neglects the relevance between the two of them. In recent years, the research on the joint extraction model has achieved encouraging results in the general field, yet scholarship focusing on the joint extraction model applied to medical field is insufficient. In this paper, we construct a joint extraction model based on tagging scheme for Chinese medical texts. Firstly, we design a series of pretreatment procedures for Chinese medical data to obtain effective Chinese word sequence. Then, we propose the BIOH12D1D2 tagging scheme to convert the joint extraction task into a tagging problem and to solve the overlapping entity problem. After that, we use the encoder-decoder model to obtain the tag prediction sequence. And in decoding layer, the Bert pre-training model is adopted to extract token features to enhance the feature representation ability of our model. Lastly, the joint extraction model gains a F1 value by 0.7 on CHIP-2020, which increases by 0.364 compared with the baseline.

Microbiota-Derived Short-Chain Fatty Acids Promote BMP Signaling by Inhibiting Histone Deacetylation and Contribute to Dentinogenic Differentiation in Murine Incisor Regeneration.

Microbiota and their metabolites short-chain fatty acids (SCFAs) have important roles in regulating tissue regeneration and mesenchymal stem cell (MSC) differentiation. In this study, we explored the potential effects of SCFAs on murine incisor regeneration and dental MSCs. We observed that SCFA deficiency induced by depletion of microbiota through antibiotic treatment led to lower renewal rate and delayed dentinogenesis in mice incisors. Supplementation with SCFAs in drinking water during antibiotic treatment can rescue the renewal rate and dentinogenesis effectively. In vitro, stimulation with SCFAs could promote differentiation of dental MSCs to odontoblasts. We further found that SCFAs could contribute to dentinogenic differentiation of dental MSCs by increasing bone morphogenetic protein (BMP) signal activation. SCFAs could inhibit deacetylation and increase BMP7 transcription of dental MSCs, which promoted BMP signaling. Our results suggested that SCFAs were required for incisor regeneration as well as differentiation of dental MSCs. Microbiota and their metabolites should be concerned as important factors in the tissue renewal and regeneration.

Melatonin protects embryonic development and maintains sleep/wake behaviors from the deleterious effects of fluorene-9-bisphenol in zebrafish (Danio rerio).

Environmental endocrine chemicals have various adverse effects on the development of vertebrates. Fluorene-9-bisphenol (BHPF), a substitute of bisphenol A (BPA), is widely used in commercial production. The effects of BHPF on development and behavior are unclear. Melatonin plays a protective role under many unfavorable conditions. In this study, we investigated the effects of BHPF on the development and behaviors of zebrafish and whether melatonin reverses effects induced by BHPF. Zebrafish embryos were exposed to 0.1, 10, or 1000 nmol/L BHPF with or without 1 µmol/L melatonin from 2 hours postfertilization to 6 days postfertilization. The results showed that 0.1 and 10 nmol/L BHPF had little effect on development. High-dose BHPF (1000 nmol/L) delayed the development, increased mortality and surface tension of embryonic chorions, caused aberrant expression of the key genes (ntl, shh, krox20, pax2, cmlc2) in early development detected by in situ hybridization, and damaged the CaP motor neurons, which were associated with locomotion ability detected by immunofluorescence. Melatonin addition reversed or weakened these adverse effects of BHPF on development, and melatonin alone increased surface tension as the effects of high-dose BHPF. However, all groups of BHPF exposure triggered insomnia-like behaviors, with increased waking activity and decreased rest behaviors. BHPF acted on the hypocretin (hcrt) system and upregulated the expression of sleep/wake regulators such as hcrt, hcrt receptor (hcrtr), arylalkylamine N-acetyltransferase-2 (aanat2). Melatonin recovered the alternation of sleep/wake behaviors induced by BHPF and restored abnormal gene expression to normal levels. This study showed that high-dose BHPF had adverse effects on early development and induced behavioral alternations. However, melatonin prevented BHPF-induced aberrant development and sleep/wake behaviors.

Microbial community and metabolic pathway succession driven by changed nutrient inputs in tailings: effects of different nutrients on tailing remediation.

To solve the competition problem of acidophilic bacteria and sulfate-reducing bacteria in the practical application of mine tailing bioremediation, research into the mechanisms of using different nutrients to adjust the microbial community was conducted. Competition experiments involving acidophilic bacteria and sulfate-reducing bacteria were performed by supplementing the media with yeast extract, tryptone, lactate, and glucose. The physiochemical properties were determined, and the microbial community structure and biomass were investigated using MiSeq sequencing and qRT-PCR, respectively. Four nutrients had different remediation mechanisms and yielded different remediation effects. Yeast extract and tryptone (more than 1.6 g/L) promoted sulfate-reducing bacteria and inhibited acidophilic bacteria. Lactate inhibited both sulfate-reducing and acidophilic bacteria. Glucose promoted acidophilic bacteria more than sulfate-reducing bacteria. Yeast extract was the best choice for adjusting the microbial community and bioremediation, followed by tryptone. Lactate kept the physiochemical properties stable or made slight improvements; however, glucose was not suitable for mine tailing remediation. Different nutrients had significant effects on the abundance of the second enzyme of the sulfate-reducing pathway (p < 0.05), which is the rate-limiting step of sulfate-reducing pathways. Nutrients changed the remediation effects effectively by adjusting the microbial community and the abundance of the sulfate-reducing rate-limiting enzyme.

Characterization of diterpenoids from Caesalpinia decapetala and their anti-TMV activities.

Caesalpinia decapetala is a versatile medicinal plant belonging to the Fabaceae plant family. In our survey on plant secondary metabolites to obtain bioactive substances for the development of new agricultural anti-TMV agents, the chemical constituents of C. decapetala were investigated. This investigation led to the isolation of three new and ten known diterpenoids. Their structures including absolute configurations were elucidated based on the extensive NMR spectroscopic data analyses and the time-dependent density functional theory calculations. The following biological screenings revealed that most of these diterpenoids possessed anti-TMV activities.

Comparative transcriptome analysis of Brucella melitensis in an acidic environment: Identification of the two-component response regulator involved in the acid resistance and virulence of Brucella.

Brucella melitensis, encounters a very stressful environment in phagosomes, especially low pH levels. So identifying the genes that contribute to the replication and survival within an acidic environment is critical in understanding the pathogenesis of the Brucella bacteria. In our research, comparative transcriptome with RNA-seq were used to analyze the changes of genes in normal-medium culture and in pH4.4-medium culture. The results reveal that 113 genes expressed with significant differences (|log2Ratio| ≥ 3); about 44% genes expressed as up-regulated. With GO term analysis, structural constituent of the ribosome, rRNA binding, structural molecule activity, and cation-transporting ATPase activity were significantly enriched (p-value ≤ 0.05). These genes distributed in 51 pathways, in which ribosome and photosynthesis pathways were significantly enriched. Six pathways (oxidative phosphorylation, iron-transporting, bacterial secretion system, transcriptional regulation, two-component system, and ABC transporters pathways) tightly related to the intracellular survival and virulence of Brucella were analyzed. A two-component response regulator gene in the transcriptional regulation pathway, identified through gene deletion and complementary technologies, played an important role in the resistance to the acid-resistance and virulence of Brucella.

Causes, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital.

Drug-induced liver injury (DILI) is an important liver disease in China, owing to the country's huge population and the availability of a multitude of drugs. Consequently, DILI is becoming an increasingly serious health problem. However, there is not enough relevant epidemiological data, and the clinical features of these patients are not clear. We conducted this study to report the causes and clinical features of DILI in hospitalized patients, and identify the mortality and predictive factors. We retrospectively collected and analyzed the data of all hospitalized patients whose discharge diagnosis was DILI at the Second Xiangya Hospital between January 2011 and December 2014. The data analyses were performed using SAS version 9.2. Among the 469 patients who were diagnosed with DILI at discharge, 361 met the criteria for DILI on re-evaluation. The crude annual incidence rate of DILI was 92.95 cases per 100,000 patients. Chinese herbal medicine was identified as the primary cause of DILI in 36.01 % of the patients. The overall mortality was 8.59 %. Alcohol consumption, use of antituberculosis drugs, serum total bilirubin, direct bilirubin, total protein, albumin, thrombinogen time, international normalized ratio, and the model for end-stage liver disease (MELD) score were significantly correlated with DILI-associated mortality. Among them, the MELD score and albumin were found to be independent predictors of outcome in patients with DILI. Chinese herbal medicine was the primary cause of DILI in the identified patients. The MELD score and albumin were independent predictors of outcome in patients with DILI.