Exploring the dynamic adaptive responses of Epimedium pubescens to phosphorus deficiency by Integrated transcriptome and miRNA analysis.

Phosphorus, a crucial macronutrient essential for plant growth and development. Due to widespread phosphorus deficiency in soils, phosphorus deficiency stress has become one of the major abiotic stresses that plants encounter. Despite the evolution of adaptive mechanisms in plants to address phosphorus deficiency, the specific strategies employed by species such as Epimedium pubescens remain elusive. Therefore, this study observed the changes in the growth, physiological reponses, and active components accumulation in E. pubescensunder phosphorus deficiency treatment, and integrated transcriptome and miRNA analysis, so as to offer comprehensive insights into the adaptive mechanisms employed by E. pubescens in response to phosphorus deficiency across various stages of phosphorus treatment. Remarkably, our findings indicate that phosphorus deficiency induces root growth stimulation in E. pubescens, while concurrently inhibiting the growth of leaves, which are of medicinal value. Surprisingly, this stressful condition results in an augmented accumulation of active components in the leaves. During the early stages (30 days), leaves respond by upregulating genes associated with carbon metabolism, flavonoid biosynthesis, and hormone signaling. This adaptive response facilitates energy production, ROS scavenging, and morphological adjustments to cope with short-term phosphorus deficiency and sustain its growth. As time progresses (90 days), the expression of genes related to phosphorus cycling and recycling in leaves is upregulated, and transcriptional and post-transcriptional regulation (miRNA regulation and protein modification) is enhanced. Simultaneously, plant growth is further suppressed, and it gradually begins to discard and decompose leaves to resist the challenges of long-term phosphorus deficiency stress and sustain survival. In conclusion, our study deeply and comprehensively reveals adaptive strategies utilized by E. pubescens in response to phosphorus deficiency, demonstrating its resilience and thriving potential under stressful conditions. Furthermore, it provides valuable information on potential target genes for the cultivation of E. pubescens genotypes tolerant to low phosphorus.

Gut microbiota in patients with prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Increasing evidence indicates that gut microbiota are closely related to prostate cancer. This study aims to assess the gut microbiota composition in patients with prostate cancer compared to healthy participants, thereby advancing understanding of gut microbiota's role in prostate cancer. METHODS: A systematic search was conducted across PubMed, Web of Science, and Embase databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of included studies was evaluated using the Newcastle-Ottawa Scale (NOS), and pertinent data were analyzed. The kappa score assessed interrater agreement. RESULTS: This study encompassed seven research papers, involving 250 prostate cancer patients and 192 controls. The kappa was 0.93. Meta-analysis results showed that alpha-diversity of gut microbiota in prostate cancer patients was significantly lower than in the control group. In terms of gut microbiota abundance, the ratio of Proteobacteria, Bacteroidia, Clostridia, Bacteroidales, Clostridiales, Prevotellaceae, Lachnospiraceae, Prevotella, Escherichia-Shigella, Faecalibacterium, and Bacteroides was higher in prostate cancer patients. Conversely, the abundance ratio of Actinobacteria, Bacteroidetes, Firmicutes, Selenomonadales, Veillonella, and Megasphaera was higher in the control group. CONCLUSION: Our study reveals differences in alpha-diversity and abundance of gut microbiota between patients with prostate cancer and controls, indicating gut microbiota dysbiosis in those with prostate cancer. However, given the limited quality and quantity of selected studies, further research is necessary to validate these findings.

Serotonin syndrome caused by escitalopram in Parkinson's disease psychosis: a case report.

BACKGROUND: Serotonin syndrome and Parkinson's disease (PD) are two diseases whose symptoms partially overlap; this poses challenges in distinguishing them in clinical practice. Early manifestations such as tremor, akathisia, diaphoresis, hypertonia and hyperreflexia are common in mild-to-moderate serotonin syndrome and can also occur in PD. Without prompt recognition and treatment, serotonin syndrome can rapidly progress, potentially leading to severe complications such as multiple organ failure within hours. Given their disparate treatment strategies, accurate clinical distinction is crucial for effective treatment. This case study explores a patient with serotonin syndrome triggered by escitalopram in the context of PD psychosis (PDP), providing insights into diagnosis and treatment planning. CASE PRESENTATION: A 75-year-old Asian woman with a one-year history of PD, a two-month history of PDP, and a six-year history of depression presented with symptoms including hyperreflexia, tremor, hypertonia, impaired level of consciousness, and inappropriate behavior following a recent one-month adjustment in medication. Initially suspected of being drug-induced parkinsonism or worsening PD, therapeutic drug monitoring revealed warning levels of escitalopram. Subsequent diagnoses confirmed serotonin syndrome. This syndrome may result from increased cortical serotonin activity at the serotonin2A receptor due to dopamine and serotonin imbalances in PDP, compounded by increased dopamine-mediated serotonin release. Additionally, being an intermediate metabolizer of cytochrome P450 enzyme 2C19, the patient experienced excessive escitalopram accumulation, exacerbating her condition. CONCLUSIONS: This case underscores the critical need to differentiate between symptoms of serotonin syndrome and PD, particularly in manifestations like tremor and hypertonia. Careful consideration of receptor profiles in patients with PDP is essential when selecting antidepressants to mitigate the risk of serotonin syndrome.

Chrysomycins, Anti-Tuberculosis C-Glycoside Polyketides from Streptomyces sp. MS751.

A new dimeric C-glycoside polyketide chrysomycin F (1), along with four new monomeric compounds, chrysomycins G (2), H (3), I (4), J (5), as well as three known analogues, chrysomycins A (6), B (7), and C (8), were isolated and characterised from a strain of Streptomyces sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type Mycobacterium tuberculosis and a number of clinically isolated MDR M. tuberculosis strains.

STAT1 contributes to microglial/macrophage inflammation and neurological dysfunction in a mouse model of traumatic brain injury.

Traumatic brain injury (TBI) triggers a plethora of inflammatory events in the brain that aggravate secondary injury and impede tissue repair. Resident microglia (Mi) and blood-borne infiltrating macrophages (MΦ) are major players of inflammatory responses in the post-TBI brain and possess high functional heterogeneity. However, the plasticity of these cells has yet to be exploited to develop therapies that can mitigate brain inflammation and improve the outcome after TBI. This study investigated the transcription factor STAT1 as a key determinant of proinflammatory Mi/MΦ responses and aimed to develop STAT1 as a novel therapeutic target for TBI using a controlled cortical impact model of TBI on adult male mice. TBI induced robust upregulation of STAT1 in the brain at the subacute injury stage, which occurred primarily in Mi/MΦ. Intraperitoneal administration of fludarabine, a selective STAT1 inhibitor, markedly alleviated proinflammatory Mi/MΦ responses and brain inflammation burden after TBI. Such phenotype-modulating effects of fludarabine on post-TBI Mi/MΦ were reproduced by tamoxifen-induced, selective knockout of STAT1 in Mi/MΦ (STAT1 mKO). By propelling Mi/MΦ away from a detrimental proinflammatory phenotype, STAT1 mKO was sufficient to reduce long-term neurological deficits and brain lesion size after TBI. Importantly, short-term fludarabine treatment after TBI elicited long-lasting improvement of TBI outcomes, but this effect was lost on STAT1 mKO mice. Together, our study provided the first line of evidence that STAT1 causatively determines the proinflammatory phenotype of brain Mi/MΦ after TBI. We also showed promising preclinical data supporting the use of fludarabine as a novel immunomodulating therapy to TBI.SIGNIFICANCE STATEMENTThe functional phenotype of microglia and macrophages (Mi/MΦ) critically influences brain inflammation and the outcome after traumatic brain injury (TBI); however, no therapies have been developed to modulate Mi/MΦ functions to treat TBI. Here we report for the first time that the transcription factor STAT1 is a key mediator of proinflammatory Mi/MΦ responses in the post-TBI brain, the specific deletion of which ameliorates neuroinflammation and improves long-term functional recovery after TBI. We also show excellent efficacy of a selective STAT1 inhibitor fludarabine against TBI-induced functional deficits and brain injury using a mouse model, presenting STAT1 as a promising therapeutic target for TBI.

Targeted ablation of signal transducer and activator of transduction 1 alleviates inflammation by microglia/macrophages and promotes long-term recovery after ischemic stroke.

BACKGROUND: Brain microglia and macrophages (Mi/MΦ) can shift to a harmful or advantageous phenotype following an ischemic stroke. Identification of key molecules that regulate the transformation of resting Mi/MΦ could aid in the development of innovative therapies for ischemic stroke. The transcription factor signal transducer and activator of transduction 1 (STAT1) has been found to contribute to acute neuronal death (in the first 24 h) following ischemic stroke, but its effects on Mi/MΦ and influence on long-term stroke outcomes have yet to be determined. METHODS: We generated mice with tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1 driven by Cx3cr1CreER. Expression of STAT1 was examined in the brain by flow cytometry and RNA sequencing after ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The impact of STAT1 mKO on neuronal cell death, Mi/MΦ phenotype, and brain inflammation profiles were examined 3-5 days after MCAO. Neurological deficits and the integrity of gray and white matter were assessed for 5 weeks after MCAO by various neurobehavioral tests and immunohistochemistry. RESULTS: STAT1 was activated in Mi/MΦ at the subacute stage (3 days) after MCAO. Selective deletion of STAT1 in Mi/MΦ did not alter neuronal cell death or infarct size at 24 h after MCAO, but attenuated Mi/MΦ release of high mobility group box 1 and increased arginase 1-producing Mi/MΦ 3d after MCAO, suggesting boosted inflammation-resolving responses of Mi/MΦ. As a result, STAT1 mKO mice had mitigated brain inflammation at the subacute stage after MCAO and less white matter injury in the long term. Importantly, STAT1 mKO was sufficient to improve functional recovery for at least 5 weeks after MCAO in both male and female mice. CONCLUSIONS: Mi/MΦ-targeted STAT1 KO does not provide immediate neuroprotection but augments inflammation-resolving actions of Mi/MΦ, thereby facilitating long-term functional recovery after stroke. STAT1 is, therefore, a promising therapeutic target to harness beneficial Mi/MΦ responses and improve long-term outcomes after ischemic stroke.

Monitoring anti-CD19 chimeric antigen receptor T cell population by flow cytometry and its consistency with digital droplet polymerase chain reaction.

Anti-CD19 chimeric antigen receptor (CAR19) T cell therapy has produced impressive clinical efficacy in patients with relapsed or refractory B-cell malignancies. As a living drug, monitoring the pharmacokinetics of CAR T cells in vivo is an important part of clinical work, which provides valuable information for assessing therapeutic response and related side effects. However, no guidelines are available regarding the detection and quantification of CAR T cells. Flow cytometry is a convenient and commonly used method in monitoring CAR T cell kinetics, but its performance remains to be validated. By using a commercial anti-idiotype antibody that detects unique epitopes on the most popular CAR19 construct, we evaluated important performance parameters, including specificity, lower limit of detection, lower limit of quantification, and precision of flow cytometry in the detection and quantification of CAR19 T cells. Consistency between the results generated by flow cytometry and droplet digital PCR was then investigated in 188 pairs of clinical data and in cell line experiments. Rabbit anti-mouse FMC63 monoclonal antibody possesses high specificity in the detection of CAR19 positive cells by FCM with a cut-off value of 0.05%. The results produced by flow cytometry and ddPCR were well correlated in the clinical samples and in cell lines, but the correlation deteriorated as the abundance of CAR19 positive cells decreased. This was especially evident with less than 0.5% of lymphocytes in clinical data, possibly due to reduced precision (indicated by intra- and inter-assay coefficients of variability) of both droplet digital PCR and flow cytometry. We demonstrated that flow cytometry using anti-idiotype antibody is a reliable and robust approach in the detection and quantification of CAR19 T cells in vivo and has good consistency with droplet digital PCR in monitoring CAR19 T cell kinetics.

Efficacy and safety of minimally invasive percutaneous nephrolithotomy versus retrograde intrarenal surgery in the treatment of upper urinary tract stones (> 1 cm): a systematic review and meta-analysis of 18 randomized controlled trials.

BACKGROUND: The advantages and disadvantages of retrograde intrarenal surgery (RIRS) and minimally invasive percutaneous nephrolithotomy (mPCNL) for treatment of upper urinary tract calculi have not been conclusively determined. METHODS: In this meta-analysis, We comprehensively evaluated the performance of the two surgical approaches in treatment of upper urinary calculi. We searched the Pubmed, Embase, Cochrane and Web of science databases for randomized controlled trial (RCT) articles on RIRS and mPCNL upto December 2022. Data were extracted by two independent reviewers and subjected to the meta-analysis using the Stata 15.1 software (StataSE, USA). RESULTS: A total of 18 eligible RCTs involving 1733 patients were included in this study. The meta-analysis revealed that mPCNL of 1-2 cm or 2-3 cm stones had a higher stone clearance rate (RR:1.08, 95%CI (1.03, 1.14), p = 0.002) and shorter operation time (WMD : -10.85 min, 95%CI (-16.76, -4.94), p<0.001). However, it was associated with more hospital stay time (WMD :1.01 day, 95%CI(0.53, 1.5), p<0.001), hemoglobin drops (WMD :0.27 g/dl, 95%CI (0.14, 0.41), p<0.001), blood transfusion rate (RR:5.04, 95%CI(1.62, 15.65), p = 0.005), pain visual analogue score (WMD:0.75, 95%CI (0.04, 1.46), p = 0.037), hospital costs (SMD :-0.97, 95%CI (-1.19, -0.76), p<0.001) and major complications (RR:1.89, 95%CI(1.01, 3.53), p = 0.045). CONCLUSION: Therefore, in terms of surgical effects and operation time, mPCNL is superior to RIRS, but is inferior with regards to other perioperative parameters. These factors should be fully considered in clinical decision making.

A systematic review and meta-analysis of outcomes between dusting and fragmentation in retrograde intrarenal surgery.

OBJECTIVES: Comparing stone-free rates and associated outcome measures between two surgical modalities of lithotripsy fragmentation and removal or spontaneous passage of dust during retrograde intrarenal surgery (RIRS). METHODS: In March 2023, we conducted a literature search in several widely used databases worldwide, including PubMed, Embase, and Google Scholar. We only considered English articles and excluded pediatric patients. Reviews and protocols without any published data were excluded. We also excluded articles with conference abstracts and irrelevant content. We used the Cochran-Mantel-Haenszel method and random-effects models to assess inverse variances and 95% confidence intervals (CIs) for mean differences in categorical variables. The results were reported as odds ratios (ORs) and 95% CIs. Statistical significance was set at p < 0.05. RESULTS: Our final meta-analysis included nine articles, comprising two randomized controlled trials (RCTs) and seven cohort studies. The total number of patients included in these studies was 1326, and all studies used holmium laser lithotripsy. The pooled analysis of the dust and fragmentation groups showed that the fragmentation group had a higher stone-free rate (OR 0.6; 95% CI 0.41 - 0.89; p = 0.01); the dust group had a shorter operative time (WMD - 11.6 min; 95% CI - 19.56 - -3.63; p = 0.004); and the dust group had a higher retreatment rate (OR 2.03; 95% CI 1.31 - 3.13; p = 0.001). There was no statistically significant difference between the two groups in terms of length of hospital stay, overall complications, or postoperative fever. CONCLUSIONS: Our results showed that both procedures could be safely and effectively used for upper ureteral and renal calculi lithotripsy, the dust group had potential advantages over the fragmentation group in terms of the operation time, and the fragmentation group had certain advantages in terms of stone-free rate and retreatment rate.

Detection of cytomegalovirus (CMV) by digital PCR in stool samples for the non-invasive diagnosis of CMV gastroenteritis.

BACKGROUND: CMV gastroenteritis is common in patients receiving allogeneic hematopoietic stem cell transplantation and it is difficult to distinguish from acute graft-versus-host disease (aGvHD), which has very similar symptoms but needs quite different treatment. CMV gastroenteritis is caused by local infection or reactivation of CMV in the gastrointestinal tract while aGvHD is due to immune rejection. The gold standard of diagnosis of CMV gastroenteritis and aGvHD is gastrointestinal biopsy under endoscopy, which is invasive and can potentially lead to severe side effects. Stool samples testing with quantitative polymerase chain reaction (qPCR) may be an alternative, while the application in trace level measurements and precision are not all satisfactory enough in reported research. METHODS: In this study, we designed a novel method that extracted the cell free DNA (cfDNA) from the fecal supernatant to perform digital PCR (dPCR) for the detection of CMV, analyzed the performance and compared it with the total DNA extracted by the current procedure. RESULTS: Twenty-two paired stool samples using two DNA extraction methods proved that the cfDNA extraction method had markedly higher DNA concentrations and control gene copy number, suggesting that cfDNA may be more informative and more useful for the detection of CMV DNA segment. The dPCR approach in detecting CMV DNA segment also exhibit good linearity (R2 = 0.997) and higher sensitivity (limit of detection at 50% was 3.534 copies/µL). Eighty-two stool samples from 44 immunocompromised patients were analyzed, CMV-positive rate was 28%, indicating that more than one-quarter of the gastrointestinal symptoms within these patients may be caused by CMV infection or reactivation. CONCLUSION: The combined results suggest that detection of CMV by dPCR in cfDNA of stool supernatant is a powerful method to identify CMV gastroenteritis and helps in clinical treatment decision making.

Obesity is associated with subclinical hypothyroidism in the presence of thyroid autoantibodies: a cross-sectional study.

BACKGROUND: Both obesity and subclinical hypothyroidism (SCH) have adverse effects on human body, but the relationship between these two conditions remains inconsistent. The presence of thyroid autoantibodies influences thyroid hormone levels, and may further mediate the interaction between obesity and SCH. This study aimed to explore the association among obesity, SCH and thyroid autoantibodies. METHODS: This study was a cross-sectional survey of 2505 subjects. Obesity was defined as a body mass index ≥28 kg/m2. Serum concentrations of thyroid hormones, thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) were examined. Logistic analysis was used to explore the relation among obesity, SCH and thyroid autoantibodies. RESULTS: A proportion of 11.54% (289/2505) subjects were obese, and 165 subjects had SCH. The positive rates of thyroid autoantibodies, TPO-Ab and Tg-Ab were 17.64% (442/2505), 11.02% (276/2505) and 14.13% (354/2505), respectively. The proportion of SCH was significantly higher in obese than nonobese subjects among those with positive thyroid autoantibodies [22.41% (13/58) vs. 11.72% (45/384), p = 0.025, χ2 test]. Moreover, obesity was significantly associated with SCH in the presence of thyroid autoantibodies after adjusting for confounding factors (OR 2.212, 95% CI 1.103 to 4.433, p = 0.025). A higher proportion of subjects with obesity had Tg-Ab positivity [17.99% (52/289) vs. 13.63% (302/2216), p = 0.045, χ2 test], and obesity remained significantly associated with Tg-Ab positivity by multiple logistic analysis (OR 1.504, 95% CI 1.077 to 2.101, p = 0.017). CONCLUSIONS: Obesity was associated with SCH in the presence of thyroid autoantibodies. Examination of SCH is recommended in obese subjects with thyroid autoantibody positivity.

Evaluation of cell-free DNA accuracy as diagnostic biomarker for prostate cancer: A systematic review and meta-analysis.

PURPOSE: This updated meta-analysis aimed to assess the diagnostic performance of circulating cell-free DNA (cf-DNA) for prostate cancer (PCa). METHODS: A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase databases to retrieve related studies. Several diagnostic estimates, including sensitivity (SE), specificity (SP), likelihood ratios (LRs), and diagnostic odds ratio (DOR) were also used to perform the meta-synthesis. Additionally, the area under hierarchical summary receiver operating characteristic curves (AU-HSROC) was used as a global measure of test accuracy. RESULTS: Twenty-nine unique articles were enrolled in the meta-analysis. Pooled SE and SP for overall accuracy of cf-DNA in PCa were obtained as 0.54 (95% CI: 0.47-0.61) and 0.92 (95% CI: 0.88-0.95), respectively. Positive LR (PLR) was 6.8 (95% CI: 4.9-9.5, I2 : 92.98%) and negative LR (NLR) was 0.5 (95% CI: 0.43-0.58). Pooled DOR was 13.56 (95% CI: 9.49-19.37) and the AU-HSROC was 0.83 (95% CI: 0.79-0.86). CONCLUSION: The present study suggested that cf-DNA assays have comparable SE as well as remarkably higher SP (qualitative assays) than common biomarkers in the detection of PCa like prostate-specific antigen (PSA). In addition, cf-DNA assays have better performance in PCa confirmation and almost similar performance to PSA in excluding PCa patients.

Research on exercise fatigue estimation method of Pilates rehabilitation based on ECG and sEMG feature fusion.

PURPOSE: Surface electromyography (sEMG) is vulnerable to environmental interference, low recognition rate and poor stability. Electrocardiogram (ECG) signals with rich information were introduced into sEMG to improve the recognition rate of fatigue assessment in the process of rehabilitation. METHODS: Twenty subjects performed 150 min of Pilates rehabilitation exercise. Twenty subjects performed 150 min of Pilates rehabilitation exercise. ECG and sEMG signals were collected at the same time. Aftering necessary preprocessing, the classification model of improved particle swarm optimization support vector machine base on sEMG and ECG data fusion was established to identify three different fatigue states (Relaxed, Transition, Tired). The model effects of different classification algorithms (BPNN, KNN, LDA) and different fused data types were compared. RESULTS: IPSO-SVM had obvious advantages in the classification effect of sEMG and ECG signals, the average recognition rate was 87.83%. The recognition rates of sEMG and ECG fusion feature classification models were 94.25%, 92.25%, 94.25%. The recognition accuracy and model performance was significantly improved. CONCLUSION: The sEMG and ECG signal after feature fusion form a complementary mechanism. At the same time, IPOS-SVM can accurately detect the fatigue state in the process of Pilates rehabilitation. On the same model, the recognition effect of fusion of sEMG and ECG(Relaxed: 98.75%, Transition:92.25%, Tired:94.25%) is better than that of only using sEMG signal or ECGsignal. This study establishes technical support for establishing relevant man-machine devices and improving the safety of Pilates rehabilitation.

Effectiveness of comprehensive geriatric assessment intervention on quality of life, caregiver burden and length of hospital stay: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Comprehensive geriatric assessment (CGA) interventions can improve functional ability and reduce mortality in older adults, but the effectiveness of CGA intervention on the quality of life, caregiver burden, and length of hospital stay remains unclear. The study aimed to determine the effectiveness of CGA intervention on the quality of life, length of hospital stay, and caregiver burden in older adults by conducting meta-analyses of randomised controlled trials (RCTs). METHODS: A literature search in PubMed, Embase, and Cochrane Library was conducted for papers published before February 29, 2020, based on inclusion criteria. Standardised mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CIs) was calculated using the random-effects model. Subgroup analyses, sensitivity analyses, and publication bias analyses were also conducted. RESULTS: A total of 28 RCTs were included. Overall, the intervention components common in different CGA intervention models were interdisciplinary assessments and team meetings. Meta-analyses showed that CGA interventions improved the quality of life of older people (SMD = 0.12; 95% CI = 0.03 to 0.21; P = 0.009) compared to usual care, and subgroup analyses showed that CGA interventions improved the quality of life only in participants' age > 80 years and at follow-up ≤3 months. The change value of quality of life in the CGA intervention group was better than that in the usual care group on six dimensions of the 36-Item Short-Form Health Survey questionnaire (SF-36). Also, compared to usual care, the CGA intervention reduced the caregiver burden (SMD = - 0.56; 95% CI = - 0.97 to - 0.15, P = 0.007), but had no significant effect on the length of hospital stay. CONCLUSIONS: CGA intervention was effective in improving the quality of life and reducing caregiver burden, but did not affect the length of hospital stay. It is recommended that future studies apply the SF-36 to evaluate the impact of CGA interventions on the quality of life and provide supportive strategies for caregivers as an essential part of the CGA intervention, to find additional benefits of CGA interventions.

Characterization of Streptomyces sp. LS462 with high productivity of echinomycin, a potent antituberculosis and synergistic antifungal antibiotic.

A biologically active microbial strain, designated as "LS462," was isolated from a soil sample collected from Yaoli Virgin Forest of Jiangxi Province, China. The strain was able to produce a high yield of echinomycin (172 mg/l) even under nonoptimized culture conditions and is proposed to serve as a promising source of echinomycin. In this study, echinomycin exhibited strong anti-Mycobacterium tuberculosis H37Rv activity and synergistic antifungal effect with a greatly reduced dosage of posaconazole on Candida albicans SC5314. The strain belongs to the genus Streptomyces according to its morphological and 16S rDNA phylogenetic analysis. The 16S rDNA was found to have the highest sequence identity with Streptomyces fuscichromogenes (99.37% similarity). Extensive nuclear magnetic resonance and mass spectroscopic data were used to determine the structure of echinomycin. The strain S. fuscichromogenes has not been previously reported to produce echinomycin. Strain LS462 may be exploited as a new potential source for the commercial production of echinomycin. Also, this work is the first to report the new synergistic antifungal activity of echinomycin and further study of the synergistic mechanism will be helpful to guide the development of antifungal agents.

Diet and the Human Gut Microbiome: An International Review.

This review summarizes the key results of recently published studies on the effects of dietary change and nutritional intervention on the human microbiome from around the world, focusing on the USA, Canada, Europe, Asia, and Africa. It first explores mechanisms that might explain the ability of fiber-rich foods to suppress the incidence and mortality from westernized diseases, notably cancers of the colon, breast, liver, cardiovascular, infectious, and respiratory diseases, diabetes, and obesity (O'Keefe in Lancet Gastroenterol Hepatol 4(12):984-996, 2019; Am J Clin Nutr 110:265-266, 2019). It summarizes studies from Africa which suggest that disturbance of the colonic microbiome may exacerbate chronic malnutrition and growth failure in impoverished communities and highlights the importance of breast feeding. The American section discusses the role of the microbiome in the swelling population of patients with obesity and type 2 diabetes and examines the effects of race, ethnicity, geography, and climate on microbial diversity and metabolism. The studies from Europe and Asia extoll the benefits of whole foods and plant-based diets. The Asian studies examine the worrying changes from low-fat, high-carbohydrate diets to high-fat, low-carbohydrate ones and the increasing appearance of westernized diseases as in Africa and documents the ability of high-fiber traditional Chinese diets to reverse type 2 diabetes and control weight loss. In conclusion, most of the studies reviewed demonstrate clear changes in microbe abundances and in the production of fermentation products, such as short-chain fatty acids and phytochemicals following dietary change, but the significance of the microbiota changes to human health, with the possible exception of the stimulation of butyrogenic taxa by fiber-rich foods, is generally implied and not measured. Further studies are needed to determine how these changes in microbiota composition and metabolism can improve our health and be used to prevent and treat disease.

Integrated Analysis of mRNA and microRNA Elucidates the Regulation of Glycyrrhizic Acid Biosynthesis in Glycyrrhiza uralensis Fisch.

Licorice (Glycyrrhiza) is a staple Chinese herbal medicine in which the primary bioactive compound is glycyrrhizic acid (GA), which has important pharmacological functions. To date, the structural genes involved in GA biosynthesis have been identified. However, the regulation of these genes in G. uralensis has not been elucidated. In this study, we performed a comprehensive analysis based on the transcriptome and small RNAome by high-throughput sequencing. In total, we identified 18 structural GA genes and 3924 transporter genes. We identified genes encoding 2374 transporters, 1040 transcription factors (TFs), 262 transcriptional regulators (TRs) and 689 protein kinases (PKs), which were coexpressed with at least one structural gene. We also identified 50,970 alternative splicing (AS) events, in which 17 structural genes exhibited AS. Finally, we also determined that miRNAs potentially targeted 4 structural genes, and 318, 8, and 218 miRNAs potentially regulated 150 TFs, 34 TRs, and 88 PKs, respectively, related to GA. Overall, the results of this study helped to elucidate the gene expression and regulation of GA biosynthesis in G. uralensis, provided a theoretical basis for the synthesis of GA via synthetic biology, and laid a foundation for the cultivation of new varieties of licorice with high GA content.

Long noncoding RNA opa-interacting protein 5 antisense transcript 1 promotes proliferation and invasion through elevating integrin α6 expression by sponging miR-143-3p in cervical cancer.

An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in cervical cancer (CC) progression. However, the roles and underlying mechanisms of lncRNA opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) involved in the CC remain unclear. In the current study, we found that lncRNA OIP5-AS1 was upregulated in CC tissues and cell lines. High OIP5-AS1 expression was significantly correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and poor overall survival of patients with CC. Using in vitro function assays, we showed that OIP5-AS1 suppression significantly decreased the proliferation, colony formation, and invasion ability of CC cells. Moreover, we revealed that OIP5-AS1 could act as a competing endogenous RNA of miR-143-3p to regulate the ITGA6 expression. Rescue assays showed that miR-143-3p inhibitors or ITGA6 overexpression could reverse the inhibitory effects of OIP5-AS1 suppression on the proliferation and invasion in CC cells. In addition, OIP5-AS1 suppression reduced tumor growth in vivo. In conclusion, we demonstrated that OIP5-AS1 promoted proliferation and invasion of CC cells via increasing the ITGA6 expression by sponging miR-143-3p, which might be an effective therapeutic target for the treatment of patients with CC.

Oleoylethanolamide inhibits glial activation via moudulating PPARα and promotes motor function recovery after brain ischemia.

Glial activation and scar formation impede the neurological function recovery after cerebral ischemia. Oleoylethanolamide (OEA), a bioactive lipid mediator, shows neuroprotection against acute brain ischemia, however, its long-term effect, especially on glial scar formation, has not been characterized. In this research, we investigate the effect of OEA on glial activation and scar formation after cerebral ischemia in vitro and in vivo experiments. Glial scar formation in vitro model was induced by transforming growth factor ß1 (TGF-ß1) in C6 glial cell culture, and experiment model in vivo was induced by middle cerebral artery occlusion (MCAO) in mice. The protein expressions of the markers of glial activation (S100ß, GFAP, or pSmads) and glial scar (neurocan) were detected by Western blot and/or immunofluorescence staining; To evaluate the role of PPARɑ in the effect of OEA on glial activation, the PPARɑ antagonist GW6471 was used. Behavior tests were used to assay the effect of OEA on motor function recovery 14 days after brain ischemia in mice. Our results show that OEA (10-50 µM) concentration-dependently inhibited the upregulation of S100ß, GFAP, pSmads and neurocan induced by TGF-ß1 in C6 glial cells. At the same time, OEA promoted the protein expression and nuclear transportation of PPARɑ in glial cells. PPARα antagonist GW6471 abolished the effect of OEA on glial activation. In addition, we found that delay administration of OEA inhibited the astrocyte activation and promoted the recovery of motor function after brain ischemia in mice. These results indicate that OEA may be developed into a new candidate for attenuating astrocytic scar formation and improving motor function after ischemic stroke.

Mitochondrial dynamics and protective effects of a mitochondrial division inhibitor, Mdivi-1, in lipopolysaccharide-induced brain damage.

Sepsis is one of the most common reasons for mortality in Intensive Care Units. As a common but severe neurological complication, sepsis associated encephalopathy (SAE) has always been ignored and there is no generally accepted treatment. In this study, we demonstrated that Mdivi-1 ameliorated brain damage assessed by Nissl staining. Furthermore, Mdivi-1 reduced TUNEL-positive cells in hippocampus, and inhibited S100 calcium binding protein B (S100B) and neuron-specific enolase (NSE) release into plasma. Biochemical analysis also showed that Mdivi-1 protected hippocampus from oxidative stresses. Western blot analysis revealed that Mdivi-1, as a Drp1 inhibitor, inhibited LPS induced dynamin-related GTPase (Drp1) increase. Interestingly, it can also attenuate LPS induced optic atrophy 1 (OPA1) and phosphorylated Drp1 (p-Drp1) decrease. Thus Mdivi-1 protected rats from SAE, and this protective effect could be associated with its inhibition of Drp1 and its activation of p-Drp1 and OPA1. Mitochondrial dynamics may be a potential pharmacological therapeutic target for treating SAE.