Acupuncture versus tricyclic antidepressants in the prophylactic treatment of tension-type headaches: an indirect treatment comparison meta-analysis.

BACKGROUND: Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis. METHODS: We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach. RESULTS: A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23). CONCLUSION: Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence.

Pure testicular choriocarcinoma, a rare and highly malignant subtype with challenging treatment: A case report and review of the literature.

Testicular choriocarcinoma (CC) is the rarest subtype of germ cell tumours (GCTs) of the testis, with a high malignant potential and early haematogenous metastasis. Radical surgical resection should be performed primarily for histological diagnosis, while chemotherapy remains the mainstay of therapy for advanced disease. In the present study, the case of a 65-year-old male patient diagnosed with metastatic testicular CC, who did not fully respond to chemotherapy is reported. This patient underwent surgical removal of the testicular tumour, chemotherapy with etoposide and cisplatin, and radiotherapy of the intracranial lesions. Although the serum human chorionic gonadotropin (HCG) levels of the patient and most of the metastases continued decreasing during chemotherapy, complete response was not achieved after six cycles of chemotherapy. The patient refused high-dose chemotherapy and autologous stem cell transplantation due to severe side effects, and eventually developed respiratory failure on maintenance therapy with oral etoposide. A literature review was then performed, aiming to summarize the characteristics and therapeutic principles of testicular CC. In addition, the emerging therapeutic agents that could be used in maintenance therapy for GCTs, particularly for testicular CC, were also discussed. The limited clinical trials of targeted treatments showed potential benefit for long survival of patients with selected GCTs with fewer side effects. In particular, immunotherapy showed unique potential for testicular CC in preclinical studies, offering new approaches of maintenance therapy for advanced disease. Further studies should shed light on the identification of prognostic factors that predict the response to immune-based therapy in GCTs.

Probiotics for the management of irritable bowel syndrome: a systematic review and three-level meta-analysis.

OBJECTIVE: Previous systematic reviews demonstrated a potentially beneficial effect of probiotics on irritable bowel syndrome (IBS). However, these studies are either affected by the inclusion of insufficient trials or by the problem of dependent data across multiple outcomes, and an overall effect size has not been provided. We aimed to determine the effect of probiotics on IBS through a three-level meta-analysis and clarify potential effect moderators. METHODS: We searched MEDLINE, Embase, and Web of Science, screening for randomized controlled trials (RCTs) that examine the effect of probiotics on IBS. The primary outcome was the improvement in the severity of global IBS symptoms at the end of treatment. The secondary outcomes were the improvement in abdominal pain and the quality of life. The effect sizes of the probiotics were measured by using the standardized mean difference (SMD) and pooled by a three-level meta-analysis model. RESULTS: We included 72 RCTs in the analysis. The meta-analysis showed significantly better overall effect of probiotics than placebo on the global IBS symptoms (SMD -0.55, 95% CI -0.76 to -0.34, P <0.001), abdominal pain (SMD -0.89, 95% CI -1.29 to -0.5, P <0.001) and quality of life (SMD 0.99, 95% CI 0.45 to 1.54, P <0.001), respectively. Moderator analysis found that a treatment duration shorter than 4 weeks was associated with a larger effect size in all the outcomes, and Bacillus probiotics had better improvement on the abdominal pain. CONCLUSIONS: Probiotics had a short-term effect and a medium effect size on the global IBS symptoms. Treatment duration and types of probiotics affected the effect size of probiotics, and shorter durations and Bacillus probiotics were associated with better treatment effects. REGISTRATION: Open Science Framework.

Dietary interventions for pediatric patients with functional abdominal pain disorders: a systematic review and network meta-analysis.

Dietary therapies are recommended for the treatment of pediatrics with functional abdominal pain disorders (FAPDs), but the comparative effectiveness among them is unclear. Therefore, the main aim of this systematic review and meta-analysis was to compare the effectiveness of differential dietary therapies in pediatrics with functional abdominal pain disorders. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases from inception to February 28, 2023. Randomized clinical trials of dietary treatments for pediatric patients with functional abdominal pain disorders were included. The primary outcome was the improvement in abdominal pain. The secondary outcomes were changes in pain intensity and pain frequency. Thirty-one studies after screening 8695 retrieved articles were included, and 29 studies were available for network meta-analysis. Compared with placebo, fiber (RR, 4.86; 95%CI, 1.77 to 13.32; P-score = 0.84), synbiotics (RR, 3.92; 95%CI, 1.65 to 9.28; P-score = 0.75), and probiotics (RR, 2.18; 95%CI, 1.46 to 3.26; P-score = 0.46) had significantly larger effect on the improvement in abdominal pain, the three treatments had larger effect than placebo but statistically insignificant in difference in improving pain frequency and intensity. Similarly, there were no significant differences between the dietary treatments after indirect comparisons of the three outcomes.  Conclusion: Fiber supplements, synbiotics, and probiotics were efficacious in improving abdominal pain of FAPDs in children, suggested by very low or low evidence. The evidence of the efficacy of probiotics is more convincing than fiber and synbiotics when sample size and statistical power were considered. No difference in the efficacy of the three treatments. High-quality trials are needed to further investigate the efficacy of dietary interventions. What is Known: • Multiple dietary treatment options are available for functional abdominal pain disorders in the pediatric population, of which the most beneficial one is currently unknown. What is New: • This NMA found very low to low certainty of the evidence suggesting that fiber, synbiotics, and probiotics might be more efficacious in improving abdominal pain of FAPDs in children than the other dietary treatments. • There were no significant differences between active dietary treatments for changes in abdominal pain intensity.

Nitrous oxide emissions from tea plantations: A review.

Tea plantations are an important N2O source. Fertilizer-induced N2O emission factors of tea plantations are much higher than other upland agricultural ecosystems. According to the basic information on characteristics and knowledge of N2O emissions from tea plantations around the world, we comprehensively reviewed N2O emission characteristics, production process, influencing factors, and reduction measures from tea plantations. The global means of ambient N2O emission and N2O emission stimulated by nitrogen fertilizer application from tea plantations were (2.68±2.92) kg N·hm-2 and (11.29±9.45) kg N·hm-2, respectively. The fertilizer-induced N2O emission factor in tea plantations (2.2%±2.1%) was much higher than the IPCC-estimated N2O emission factor for agricultural land (1%). N2O emission from tea plantation soil (a typical acid soil) were mainly produced during nitrification and denitrification, with denitrification being dominant. N2O emission from tea plantations were significantly related to the amount of fertilizer application. Other factors, such as fertilizer type, could also affect soil N2O emissions in tea plantations. The main reduction methods of N2O emission from tea plantations included optimizing the amount and type of fertilizer, amending biochar, and rationally using nitrification inhibitors. In future, we should strengthen in-situ observations of soil N2O emission from tea plantations at both temporal and spatial scales, combine lab incubation and field studies to elucidate the mechanisms underling tea plantation soil N2O emissions, and use a data-model fusion approach to reduce uncertainties in the estimation of global N2O emission. These would provide theoretical support and practical guidance for reasonable N2O emission reduction in tea plantations.

Efficacy of acupuncture for tension-type headache prophylaxis: systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Acupuncture has been shown to reduce tension-type headache (TTH) frequency in previous studies. Nevertheless, repeated significance testing might inflate type I error. We aimed to verify the effectiveness and safety of acupuncture in reducing TTH frequency by meta-analysis and trial sequential analysis (TSA). METHODS: Ovid Medline, Embase, and Cochrane Library were searched until September 29, 2022. Randomized controlled trials comparing acupuncture with sham acupuncture, no acupuncture, or other active therapies in adults with TTH were included. The primary outcome was TTH frequency. The secondary outcomes were responder rate and adverse event. RESULTS: Fourteen studies involving 2795 participants were included. Acupuncture had more reduction than sham acupuncture in TTH frequency, both after treatment (standardized mean difference [SMD] - 0.80, 95% CI - 1.36 to - 0.24, P = 0.005) and at the follow-up period (SMD - 1.33, 95% CI - 2.18 to - 0.49, P = 0.002), while TSA showed the included sample size did not exceed required information size (RIS). Acupuncture was superior over no acupuncture after treatment (SMD - 0.52, 95% CI - 0.63 to - 0.41, P < 0.001), and cumulative sample size reached RIS. In terms of responder rate, acupuncture had a higher responder rate compared with sham acupuncture both after treatment (relative ratio [RR] 1.28, 95% CI 1.12 to 1.46, P = 0.0003) and the follow-up period (RR 1.37, 95% CI 1.19 to 1.58, P < 0.0001), but the sample size is inadequate. CONCLUSION: Acupuncture is an efficacious and safe treatment for TTH prevention, but this conclusion might be limited by the generally very low to low quality evidence. TSA suggested that high-quality trials are needed to verify the efficacy and safety of acupuncture compared to sham acupuncture.

Emerging roles of circRNAs in leukemia and the clinical prospects: An update.

BACKGROUND: Circular RNAs (circRNAs) are a new category of endogenous non-protein coding RNAs (ncRNAs), and show the characteristics of high conservation, stability, and tissue specificity. Due to rapid advances in next-generation sequencing and transcriptome profiling technologies, circRNAs have been widely discovered in many organisms and participated in the development and progress of a variety of diseases. As a type of molecular sponge, circRNAs mainly absorb micro RNAs competitively and interplay with RNA-binding proteins to modulate the splicing as well as transcription of target genes. METHODS: This review is based on a literature search using the Medline database. Search terms used were "circular RNAs and leukemia," "circRNAs and leukemia," "circRNAs and acute lymphoblastic leukemia," "circRNAs and chronic lymphoblastic leukemia," "circRNAs and acute myeloid leukemia," "circRNAs and chronic myeloid leukemia," and "circRNAs, biomarker, and hematological system." RESULTS: CircRNAs have been proven as potential biomarkers and therapeutic targets in a variety of tumors. Recent research has found that circRNAs aberrantly exist in hematological cancers, especially leukemia, and are significantly associated with the incidence, progress, and metastasis of diseases as well as the prognosis of patients. CONCLUSION: The current work summarizes the latest findings on circRNAs in various types of leukemia, aiming to propose prospective therapies and new drug screening methods for the treatment of leukemia.

Targeted isolation of antitubercular cycloheptapeptides and an unusual pyrroloindoline-containing new analog, asperpyrroindotide A, using LC-MS/MS-based molecular networking.

Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides, namely, asperversiamides A-C (1-3) and asperheptatides A-D (4-7) and an unusual pyrroloindoline-containing new cycloheptapeptide, asperpyrroindotide A (8). The structure of 8 was elucidated by comprehensive spectroscopic data analysis, and its absolute configuration was determined by advanced Marfey's method. The semisynthetic transformation of 1 into 8 was successfully achieved and the reaction conditions were optimized. Additionally, a series of new derivatives (10-19) of asperversiamide A (1) was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosis H37Ra. The preliminary structure-activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-022-00157-8.

Evaluation of the antimicrobial function of Ginkgo biloba exocarp extract against clinical bacteria and its effect on Staphylococcus haemolyticus by disrupting biofilms.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Ginkgo biloba L. (Ginkgo nuts) has been used for a long time as a critical Chinese medicine material to treat cough and asthma, as well as a disinfectant. Similar records were written in the Compendium of Materia Medica (Ben Cao Gang Mu, pinyin in Chinese) and Sheng Nong's herbal classic (Shen Nong Ben Cao Jing, pinyin in Chinese). Recent research has shown that Ginkgo biloba exocarp extract (GBEE) has the functions of unblocking blood vessels and improving brain function, as well as antitumour activity and antibacterial activity. GBEE was shown to inhibit methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation as a traditional Chinese herb in our previous report in this journal. AIM OF THE STUD: yThe antibiotic resistance of clinical bacteria has recently become increasingly serious. Thus, this study aimed to investigate the Ginkgo biloba exocarp extract (GBEE) antibacterial lineage, as well as its effect and mechanism on S. haemolyticus biofilms. This study will provide a new perspective on clinical multidrug resistant (MDR) treatment with ethnopharmacology herbs. METHODS: The microbroth dilution assay was carried out to measure the antibacterial effect of GBEE on 13 types of clinical bacteria. Bacterial growth curves with or without GBEE treatment were drawn at different time points. The potential targets of GBEE against S. haemolyticus were screened by transcriptome sequencing. The effects of GBEE on bacterial biofilm formation and mature biofilm disruption were determined by crystal violet staining and scanning electron microscopy. The metabolic activity of bacteria inside the biofilm was assessed by colony-forming unit (CFU) counting and (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2HY-tetrazolium bromide (MTT) assay. Quantitative polymerase chain reaction (qPCR) was used to measure the gene expression profile of GBEE on S. haemolyticus biofilm-related factors. RESULTS: The results showed that GBEE has bacteriostatic effects on 3 g-positive (G+) and 2 g-negative (G-) bacteria among 13 species of clinical bacteria. The antibacterial effect of GBEE supernatant liquid was stronger than the antibacterial effect of GBEE supernviaould-like liquid. GBEE supernatant liquid inhibited the growth of S. epidermidis, S. haemolyticus, and E. faecium at shallow concentrations with minimum inhibitory concentrations (MICs) of 2 µg/ml, 4 µg/ml and 8 µg/ml, respectively. Genes involved in quorum sensing, two-component systems, folate biosynthesis, and ATP-binding cassette (ABC) transporters were differentially expressed in GBEE-treated groups compared with controls. Crystal violet, scanning electron microscopy (SEM) and MTT assays showed that GBEE suppressed S. haemolyticus biofilm formation in a dose-dependent manner. Moreover, GBEE supernatant liquid downregulated cidA, cidB and atl, which are involved in cell lysis and extracellular DNA (eDNA) release, as well as downregulated the cbp, ebp and fbp participation in encoding cell-surface binding proteins. CONCLUSIONS: GBEE has an excellent antibacterial effect on gram-positive bacteria and also inhibits the growth of gram-negative bacteria, such as A. baumannii (carbapenem-resistant Acinetobacter baumannii) CRABA and S. maltophilia. GBEE inhibits the biofilm formation of S. haemolyticus by altering the regulation and biofilm material-related genes, including the release of eDNA and cell-surface binding proteins.

[Emission of Nitrous Oxide (N2O) from Lake Taihu and the Corresponding Potential Driving Factors].

Nitrous oxide (N2O) is one of the six greenhouse gases stipulated in the Kyoto Protocol. Its greenhouse potential over the past century was 298 times that of CO2, and the concentration of atmospheric N2O has been continuously and rapidly increasing during the past hundred years. Shallow lakes are an important source of atmospheric N2O. In order to explore the temporal and spatial changes and potential driving factors of N2O emissions from eutrophic water, we conducted field observations in February (winter) and August (summer) in Lake Taihu. We used the coefficient of diffusion-headspace bottle method to trace the variability in the N2O concentration[c(N2O)] and efflux[F(N2O)] from surface water bodies and explored the potential driving factors of N2O emissions. The optical measurements of dissolved organic matter (DOM) are an effective approach for tracing the source and composition of dissolved organic carbon (DOC) and dissolved organic nitrogen (DON). The migration and transformation processes of DOM also release a large amount of inorganic nitrogen, which changes the redox potential of the water column and thereby affects N2O emissions. Our results showed that the variability in c(N2O) and F(N2O) in the surface waters of Lake Taihu were strongly affected by water temperature and nutrient levels. The average c(N2O) of the surface waters was (19.7±2.7) nmol·L-1, corresponding to a mean F(N2O) of (41.1±1.8) µmol·(m2·d)-1, and the means of both c(N2O) and F(N2O) were higher in summer than those in winter (t-test, P<0.01). The input and accumulation of DOM could increase the production and emission potential of N2O in water bodies, as supported by both c(N2O) and F(N2O) significantly increasing with increasing level of terrestrial humic-like C1. The integration ratio of peak C to peak T IC:IT of DOM and the spectral slope S275-295 results indicated that there were high inputs of terrestrial DOM in the northwestern inflowing river mouths, concurring with the high production and emission of N2O found there. This suggested that the accumulation and degradation of terrestrial DOM potentially fueled the emission of N2O. Our results showed that water temperature, DOM composition, and nutrient level were all important factors affecting N2O emission from Lake Taihu. Long-term continuous observation can be applied to better evaluate the impact of various environmental factors on the production and emission of N2O in water bodies and to help with providing scientific emission reduction plans.

Gut microbiota and major depressive disorder: A bidirectional Mendelian randomization.

BACKGROUND: Observational studies showed an association between gut microbiota and depression, but the causality relationship between them is unclear. We aimed to determine whether there is a bidirectional causal relationship between the composition of gut microbiota and major depressive disorders (MDD) and explore the role of gut microbiota in decreasing the risk of MDD. METHODS: Our two-sample Mendelian randomization (MR) study acquired top SNPs associated with the composition of gut microbiota (n = 18,340) and with MDDs (n = 480,359) from publicly available genome-wide association studies (GWAS). The SNPs estimates were pooled using inverse-variance weighted meta-analysis, with sensitivity analyses-weighted median, MR Egger, and MR Pleiotropy Residual Sum and Outlier (PRESSO). RESULTS: The Actinobacteria class had protective causal effects on MDD (OR 0.88, 95%CI 0.87 to 0.9). The Bifidobacterium (OR 0.89, 95%CI 0.88 to 0.91) were further found to have similar effects as the Actinobacteria class. The genus Ruminococcus1 had a protective effect on MDD (OR 0.88, 95%CI 0.76 to 0.99) while the Streptococcaceae family and its genus had an anti-protective effect on MDD (OR 1.07, 95%CI 1.01 to 1.13), but these findings were not supported by the MR-Egger analysis. Bidirectional MR showed no effect of MDD on gut microbiota composition. LIMITATIONS: The use of summary-level data, the risk of sample overlap and low statistical power are the major limiting factors. CONCLUSIONS: Our MR analysis showed a protective effect of Actinobacteria, Bifidobacterium, and Ruminococcus and a potentially anti-protective effect of Streptococcaceae on MDD pathogenesis. Further studies are needed to transform the findings into practice.

Integrating Activity-Guided Strategy and Fingerprint Analysis to Target Potent Cytotoxic Brefeldin A from a Fungal Library of the Medicinal Mangrove Acanthus ilicifolius.

Mangrove-associated fungi are rich sources of novel and bioactive compounds. A total of 102 fungal strains were isolated from the medicinal mangrove Acanthus ilicifolius collected from the South China Sea. Eighty-four independent culturable isolates were identified using a combination of morphological characteristics and internal transcribed spacer (ITS) sequence analyses, of which thirty-seven strains were selected for phylogenetic analysis. The identified fungi belonged to 22 genera within seven taxonomic orders of one phyla, of which four genera Verticillium, Neocosmospora, Valsa, and Pyrenochaeta were first isolated from mangroves. The cytotoxic activity of organic extracts from 55 identified fungi was evaluated against human lung cancer cell lines (A-549), human cervical carcinoma cell lines (HeLa), human hepatoma cells (HepG2), and human acute lymphoblastic leukemia cell lines (Jurkat). The crude extracts of 31 fungi (56.4%) displayed strong cytotoxicity at the concentration of 50 µg/mL. Furthermore, the fungus Penicillium sp. (HS-N-27) still showed strong cytotoxic activity at the concentration of 25 µg/mL. Integrating cytotoxic activity-guided strategy and fingerprint analysis, a well-known natural Golgi-disruptor and Arf-GEFs inhibitor, brefeldin A, was isolated from the target active strain HS-N-27. It displayed potential activity against A549, HeLa and HepG2 cell lines with the IC50 values of 101.2, 171.9 and 239.1 nM, respectively. Therefore, combining activity-guided strategy with fingerprint analysis as a discovery tool will be implemented as a systematic strategy for quick discovery of active compounds.

Circ_KCNQ5 participates in the progression of childhood acute myeloid leukemia by enhancing the expression of RAB10 via binding to miR-622.

BACKGROUND: : Acute myeloid leukemia (AML) is regarded as a haematological malignancy and seriously threatens the public's health. Circular RNA (circRNA) is gradually confirmed to be involved in the development of AML. The purpose of this study was to disclose the role of circRNA Potassium Voltage-Gated Channel Subfamily Q Member 5 (circ_KCNQ5) in AML. METHODS: : Quantitative real-time PCR (qPCR) and western blot were used for expression analysis. Colony formation assay, EdU assay and MTT assay were performed to determine cell proliferation. Flow cytometry assay was conducted to determine cell apoptosis. The predicted binding relationship between miR-622 and circ_KCNQ5 or RAS oncogene family member 10 (RAB10) was verified by dual-luciferase reporter assay. RESULTS: : The expression of circ_KCNQ5 was increased in bone marrow samples of childhood AML patients and AML cell lines. The knockdown of circ_KCNQ5 largely suppressed AML cell proliferation and promoted cell apoptosis. Circ_KCNQ5 directly bound to miR-622 and inhibited miR-622 expression. The cotransfection of miR-622 inhibitor reversed the effects of circ_KCNQ5 knockdown and thus recovered cell proliferation and depleted cell apoptosis. RAB10 was a target of miR-622, and circ_KCNQ5 bound to miR-622 to increase the expression of RAB10. MiR-622 restoration inhibited AML cell proliferation and induced cell apoptosis, while RAB10 overexpression abolished these effects. CONCLUSION: : Circ_KCNQ5 high expression was associated with childhood AML malignant development, and circ_KCNQ5 participated in AML progression by regulating the miR-622/RAB10 pathway.

The Fusaric Acid Derivative qy17 Inhibits Staphylococcus haemolyticus by Disrupting Biofilm Formation and the Stress Response via Altered Gene Expression.

Staphylococcus haemolyticus (S. haemolyticus) is the second most commonly isolated coagulase-negative staphylococcus (CoNS) in patients with hospital-acquired infections. It can produce phenol-soluble modulin (PSM) toxins and form biofilms. Compared with the wealth of information on Staphylococcus aureus and Staphylococcus epidermidis, very little is known about S. haemolyticus. There is an urgent need to find an effective preparation to combat the harm caused by S. haemolyticus infection. Chinese herbs have been utilized to cure inflammation and infectious diseases and have a long history of anticancer function in China. Here, we modified fusaric acid characterized from the metabolites of Gibberella intermedia, an endophyte previously isolated from Polygonum capitatum. This study shows that fusaric acid analogs (qy17 and qy20) have strong antibacterial activity against S. haemolyticus. In addition, crystal violet analyses and scanning electron microscopy observations demonstrated that qy17 inhibited biofilm formation and disrupted mature biofilms of S. haemolyticus in a dose-dependent manner. Additionally, it reduced the number of live bacteria inside the biofilm. Furthermore, the antibiofilm function of qy17 was achieved by downregulating transcription factors (sigB), transpeptidase genes (srtA), and bacterial surface proteins (ebp, fbp) and upregulating biofilm-related genes and the density-sensing system (agrB). To further elucidate the bacteriostatic mechanism, transcriptomic analysis was carried out. The following antibacterial mechanisms were uncovered: (i) the inhibition of heat shock (clpB, groES, groL, grpE, dnaK, dnaJ)-, oxidative stress (aphC)- and biotin response (bioB)-related gene expression, which resulted in S. haemolyticus being unable to compensate for various stress conditions, thereby affecting bacterial growth; and (ii) a reduction in the expression of PSM-beta (PSMß1, PSMß2, PSMß3) toxin- and Clp protease (clpP, clpX)-related genes. These findings could have major implications for the treatment of diseases caused by S. haemolyticus infections. Our research reveals for the first time that fusaric acid derivatives inhibit the expression of biofilm formation-related effector and virulence genes of S. haemolyticus. These findings provide new potential drug candidates for hospital-acquired infections caused by S. haemolyticus.

Functional and expression characteristics identification of Phormicins, novel AMPs from Musca domestica with anti-MRSA biofilm activity, in response to different stimuli.

Antibiotic-resistant bacteria (including MRSA) in the clinic pose a growing threat to public health, and antimicrobial peptides (AMPs) have great potential as efficient treatment alternatives. Houseflies have evolved over long periods in complex, dirty environments, developing a special immune system to overcome challenges in harmful environments. AMPs are key innate immune molecules. Herein, two differentially expressed AMPs, Phormicins A and B, were identified by screening transcriptomic changes in response to microbial stimulation. Structural mimic assays indicated that these AMPs exhibited functional divergence due to their C-terminal features. Expression analysis showed that they had different expression patterns. Phormicin B had higher constitutive expression than Phormicin A. However, Phormicin B was sharply downregulated, whereas Phormicin A was highly upregulated, after microbial stimulation. The MIC, MBC and time-growth curves showed the antibacterial spectrum of these peptides. Crystal violet staining and SEM showed that Phormicin D inhibited MRSA biofilm formation. TEM suggested that Phormicin D disrupted the MRSA cell membrane. Furthermore, Phormicin D inhibited biofilm formation by downregulating the expression of biofilm-related genes, including altE and embp. Therefore, housefly Phormicins were functionally characterized as having differential expression patterns and antibacterial & antibiofilm activities. This study provides a new potential peptide for clinical MRSA therapy.

Low FODMAP Diet and Probiotics in Irritable Bowel Syndrome: A Systematic Review With Network Meta-analysis.

Background: Probiotic and low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet are two commonly used management approaches for patients with irritable bowel syndrome (IBS). We aimed to evaluate the most effective combinations and components among different probiotics or low FODMAP diet through component network meta-analysis (NMA). Methods: We searched Embase, Ovid Medline, and Web of Science from inception to 21 January 2021. Randomized controlled trials (RCTs) examining the efficacy of probiotics and low FODMAP diet for IBS were included, with placebo, sham diet, or conventional treatments as controls. Binary outcomes were compared among treatments using the relative ratio (RR). A minimally contextualized framework recommended by the GRADE group was used to evaluate the certainty of evidence. The primary efficacy outcome was the relief of global IBS symptoms, and the secondary efficacy outcome was the reduction in IBS symptom scores or abdominal pain scores. Key Results: We included 76 RCTs (n = 8058) after screening 1940 articles. Eight RCTs were classified as low risk of bias. Standard network meta-analysis (NMA) showed that Lactobacillus (RR 1.74, 95% CI 1.22-2.48) and Bifidobacterium (RR 1.76, 95% CI 1.01-3.07) were the most effective for the primary efficacy outcome (high certainty evidence); component NMA showed that Bacillus (RR 5.67, 95% CI 1.88 to 17.08, p = 0.002) and Lactobacillus (RR 1.42, 95% CI 1.07 to 1.91, p = 0.017) were among the most effective components. The results of standard NMA and CNMA analysis of the improvement of overall IBS symptom scores or abdominal pain scores were consistent with this finding. Conclusion: Lactobacillus was the most effective component for the relief of IBS symptoms; Bifidobacterium and Bacillus were possibly effective and need further verification. Systematic Review Registration: website, identifier registration number.

Design, Semisynthesis, Insecticidal and Antibacterial Activities of a Series of Marine-Derived Geodin Derivatives and Their Preliminary Structure-Activity Relationships.

To enhance the biological activity of the natural product geodin (1), isolated from the marine-derived fungus Aspergillus sp., a series of new ether derivatives (2-37) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically. Most of these derivatives showed better insecticidal activities against Helicoverpa armigera Hübner than 1. In particular, 15 showed potent insecticidal activity with an IC50 value of 89 µM, comparable to the positive control azadirachtin (IC50 = 70 µM). Additionally, 5, 12, 13, 16, 30 and 33 showed strong antibacterial activity against Staphylococcus aureus and Aeromonas salmonicida with MIC values in the range of 1.15-4.93 µM. The preliminary structure-activity relationships indicated that the introduction of halogenated benzyl especially fluorobenzyl, into 1 and substitution of 4-OH could be key factors in increasing the insecticidal and antibacterial activities of geodin.

Two new Botryosphaeria (Botryosphaeriales, Botryosphaeriaceae) species in China.

Five ascomycetous strains were isolated from dead branches and leaves of Salix (Salicaceae) and Osmanthusfragrans (Oleaceae), respectively. BLAST searches with ITS sequences in GenBank suggested a high degree of similarity to Botryosphaeriadothidea. To accurately identify these strains, we further analysed their morphological characteristics of asci, ascospores, all conidiophore cells and conidia. Phylogenetic relationships, based on ITS, rpb2, tef1 and tub2 gene sequences, confirmed our strains represented two novel species, which are introduced here as B.salicicola and B.osmanthuse spp. nov.

Association between body mass index and mortality among older Chinese: evidence from CHARLS / 预防医学

Objective@#To investigate the association between body mass index ( BMI ) and mortality risk among older Chinese based on the China Health and Retirement Longitudinal Study ( CHARLS ). @*Methods@#The demographic features, BMI, prevalence of chronic diseases and mortality among the elderly at ages of 60 years and greater were captured from the CHARLS database from 2011 to 2018. A multivariable Cox proportional hazards regression model was used to examine the association between BMI and the risk of death.@*Results@#Totally 6 023 subjects were enrolled, including 3 006 men ( 50.09% ) and 3 017 women ( 49.91% ), and 68.69% of the participants ( 4 137 subjects ) were at ages of 60 to 69 years. There were 637 subjects ( 10.58% ) with underweight, 1 544 ( 25.63% ) with overweight, and 557 ( 9.25% ) with obesity. During the follow-up period ( 35 091 person-years ), 1 035 subjects died. Multivariable Cox proportional hazards regression analysis revealed an increased risk of mortality among the underweight elderly ( HR=1.496, 95%CI: 1.261-1.775 ) and a reduced risk of mortality among the obese elderly ( HR=0.671, 95%CI: 0.511-0.881 ) relative to the elderly with normal weight, after adjustment for age, gender, smoking, household registration, administration of anti-diabetic drugs, administration of anti-dyslipidemia drugs, and administration of anti-hypertensive drugs.@*Conclusion@#It is found that the risk of mortality among the Chinese elderly correlatives with BMI through the analysis of CHARLS data.

[Correlation of Plasma MiR-146a, MiR-223 Levels with the Prognosis of Childhood with Acute Lymphoblastic Leukemia].

OBJECTIVE: To observe the expression of plasma microRNA (miR)-146a and miR-223 in children with acute lymphoblastic leukemia (ALL), so as to analyze the relationship between the two factors and the prognosis of children with ALL. METHODS: 100 children with ALL treated in the hospital from January 2015 to December 2017 were selected, according to the standard of Chinese Children's Leukemia Group (CCLG)-ALL-2008 program, the children were performed standardized treatment in our hospital according to different risk degree, the follow-up results were obtained, the follow-up time was ≥36 months, and the follow-up time was till to March 2021, the recurrence and mortality of the children were used as prognostic indicators; the baseline data of the children at admission were inquired and recorded, the plasma miR-146a and miR-223 levels were analyzed at admission, and their correlation with the prognosis of children with ALL was analyzed. RESULTS: During the follow-up period, 4 cases of children died while 18 cases recurred, which means 22(22.00%) children showed the poor prognosis; the plasma miR-146a level of the children in poor prognosis group at admission was higher than those in good prognosis group, while the plasma miR-223 level was lower than those in good prognosis group, the differences showed statistically significantly (P<0.05); the results of regression analysis showed that the over expression of plasma miR-146a and low expression of plasma miR-223 at admission might be associated with poor prognosis in ALL children, and might be a risk factor for poor prognosis in children (P<0.05); the ROC curve showed that the AUC of plasma miR-146a and miR-223 at admission alone or in combination showed the predictive value for the risk of poor prognosis in children with ALL(AUC >0.80); the results of correlation test showed that there was a negative correlation of plasma miR-146a with miR-223 levels at admission (r=-0.239, P=0.016). CONCLUSION: Plasma miR-146a is overexpressed and miR-223 is low-expressed in children with ALL, the abnormal expression of the two factors is related to the prognosis of children with ALL.