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•208 endophytic fungal isolates were collected from stems (83), leaves (121) and flowers (4) of 26 medicinal plants.•Fifteen endophytic fungi exhibited antifungal activity.•Strain of ...L. pseudotheobromae has strong biological control of wheat powdery mildew.•The first report of L. pseudotheobromae having antifungal activity against plant pathogens.
Many medicinal plants possess antimicrobial activities, and have antagonistic endophytic fungi that help them protect from pathogen attack. The aim of this study was to examine endophytic fungi in traditional Chinese medicinal plants, and understand if these organisms have antimicrobial activities and they can be potentially used for biological control of plant diseases. A total of 208 endophytic fungal isolates were collected from stems (83), leaves (121) and flowers (4) of 26 medicinal plant species. The majority of the isolates belonged to Alternaria, Phomopsis, Colletotrichum, Phoma and Acremonium as well as several species allocated to Mycelia sterilia. A detached leaf assay was conducted by testing these isolates on wheat powdery mildew (Blumeria graminis f. sp. tritici, or Bgt). Fifteen isolates of endophytic fungi inhibited Bgt, exhibiting control efficacies ranging from 65.4% to 100%. Of these isolates, LPS-1, SCS-6 and 16-6, exhibited significant inhibition of Bgt proliferation (>90%). Isolate LPS-1 isolated from the stem of Ilex cornuta Lindl. ex Paxt. had the highest efficacy, resulting in 100% inhibition of Bgt growth on detached leaf segments. Based on morphological characteristics and phylogenetic analyses of the ITS rDNA sequences and translation elongation factor 1-alpha (TEF-1α) gene regions, LPS-1 was identified as Lasiodiplodia pseudotheobromae. A range of culture conditions for LPS-1 were examined and the results indicated that optimal antifungal activity resulted from static cultures in PDB (pH 7.0) inoculated with three mycelial plugs and incubated at 30°C for 6days. With further study, LPS-1 can be a candidate for biological control.
Congenital heart malformation (CHM) is the most common form of congenital human birth anomaly and is the leading cause of infant mortality. Although some causative genes have been identified, little ...progress has been made in identifying genes in which low-penetrance susceptibility variants occur in the majority of sporadic CHM cases. To identify common genetic variants associated with sporadic non-syndromic CHM in Han Chinese populations, we performed a multistage genome-wide association study (GWAS) in a total of 4,225 CHM cases and 5,112 non-CHM controls. The GWAS stage included 945 cases and 1,246 controls and was followed by 2-stage validation with 2,160 cases and 3,866 controls. The combined analyses identified significant associations (P < 5.0 × 10⁻⁸) at 1p12 (rs2474937 near TBX15; odds ratio (OR) = 1.40; P = 8.44 × 10⁻¹⁰) and 4q31.1 (rs1531070 in MAML3; OR = 1.40; P = 4.99 × 10⁻¹²). These results extend current knowledge of genetic contributions to CHM in Han Chinese populations.
The discovery of natural bioactive compounds from endophytes or medicinal plants against plant diseases is an attractive option for reducing the use of chemical fungicides. In this study, three ...compounds, indole-3-carbaldehyde, indole-3-carboxylic acid (3-ICA), and jasmonic acid (JA), were isolated from the EtOAc extract of the culture filtrate of the endophytic fungus
Lasiodiplodia pseudotheobromae
LPS-1, which was previously isolated from the medicinal plant,
Ilex cornuta
. Some experiments were conducted to further determine the antifungal activity of these compounds on wheat powdery mildew. The results showed that JA was much more bioactive than indole-3-carbaldehyde and 3-ICA against
Blumeria graminis
, and the disease severity caused by
B. graminis
decreased significantly with the concentration increase of JA treatment. The assay of the interaction of 3-ICA and JA indicated that there was a significant synergistic effect between the two compounds on
B. graminis
in each of the ratios of 3-ICA to JA (3-ICA:JA) ranging from 1:9 to 9:1. When the compound ratio of 3-ICA to JA was 2:8, the synergistic coefficient was the highest as 22.95. Meanwhile, a histological investigation indicated that, under the treatment of JA at 500 μg/ml or 3-ICA:JA (2:8) at 40 μg/ml, the appressorium development and haustorium formation of
B. graminis
were significantly inhibited. Taken together, we concluded that JA plays an important role in the infection process of
B. graminis
and that 3-ICA as a synergist of JA enhances the antagonism against wheat powdery mildew.
Perioperative neurocognitive disorder (PND) is a common complication following thoracic surgery that frequently occurs in patients ≥65 years. PND includes postoperative cognitive dysfunction (POCD) ...and postoperative delirium (POD). To investigate whether intravenous dexmedetomidine (DEX) is able to improve neurocognitive function in elderly male patients following thoracoscopic lobectomy, a randomized, double-blinded, placebo-controlled trial was performed at the Affiliated Hospital of Inner Mongolia Medical University (Hohhot, China). Patients aged ≥65 years were enrolled and were subjected to thoracic surgery under general anesthesia. A computer-generated randomization sequence was used to randomly assign patients (at a 1:1 ratio) to receive either intravenous DEX (0.5 µg/kg per h, from induction until chest closure) or placebo (intravenous normal saline). The primary endpoint was the result of the Mini-Mental State Examination (MMSE). The secondary endpoints were the results of the Montreal Cognitive Assessment (MoCA) and those obtained with the Confusion Assessment Method (CAM), as well as the incidence of POCD and POD during the first 7 postoperative days. Other observational indexes included sleep quality at night, self-anxiety scale prior to the operation and 7 days following the operation and the visual analogue scale (VAS) score at rest and during movement on the first and third day following the operation. Furthermore, at 6 h following surgery, the MMSE score in the DEX group was significantly higher than that in the saline group. At 6 h and on the first day postoperatively, the MoCA score in the DEX group was significantly higher than that in the saline group. The incidence of POCD and POD in the DEX group was 13.2 and 7.5%, respectively, while that in the saline group was 35.8 and 11.3%, respectively. There was a significant difference in the incidence of POCD between the two groups (P<0.01). In the DEX group, mean sleep quality was increased, whereas the mean VAS was decreased compared with the corresponding values in the saline group. In conclusion, elderly male patients who underwent thoracoscopic lobectomy under continuous infusion of DEX (0.5 µg/kg/h) exhibited a reduced incidence of POCD during the first 7 postoperative days as compared with the placebo group. Furthermore, DEX improved the subjective sleep quality in the first postoperative night, reduced anxiety and alleviated postoperative pain. In addition, it increased the incidence of bradycardia. The present study was registered in the Chinese Clinical Trial Registry (www.chictr.org.cn; registration no. ChiCTR-IPR-17010958).
We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy and safety of mazdutide, a once-weekly glucagon-like peptide 1 and glucagon receptor dual agonist, ...in Chinese patients with type 2 diabetes.
Adults with type 2 diabetes inadequately controlled with diet and exercise alone or with stable metformin (glycated hemoglobin A1c HbA1c 7.0-10.5% 53-91 mmol/mol) were randomly assigned to receive 3 mg mazdutide (n = 51), 4.5 mg mazdutide (n = 49), 6 mg mazdutide (n = 49), 1.5 mg open-label dulaglutide (n = 50), or placebo (n = 51) subcutaneously for 20 weeks. The primary outcome was change in HbA1c from baseline to week 20.
Mean changes in HbA1c from baseline to week 20 ranged from -1.41% to -1.67% with mazdutide (-1.35% with dulaglutide and 0.03% with placebo; all P < 0.0001 vs. placebo). Mean percent changes in body weight from baseline to week 20 were dose dependent and up to -7.1% with mazdutide (-2.7% with dulaglutide and -1.4% with placebo). At week 20, participants receiving mazdutide were more likely to achieve HbA1c targets of <7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol) and body weight loss from baseline of ≥5% and ≥10% compared with placebo-treated participants. The most common adverse events with mazdutide included diarrhea (36%), decreased appetite (29%), nausea (23%), vomiting (14%), and hypoglycemia (10% 8% with placebo).
In Chinese patients with type 2 diabetes, mazdutide dosed up to 6 mg was generally safe and demonstrated clinically meaningful HbA1c and body weight reductions.
Infection in male and female genital tracts can lead to infertility. The underlying mechanisms of this process remain unclear. Toll-like receptors (TLRs) recognize conserved structures and respond to ...pathogens by initiating signals that activate inflammatory gene transcription. Here, we demonstrate that TLR activation in sperm reduces sperm motility via signalling through myeloid differentiation factor 88 (MyD88), phosphatidylinositol 3-kinase (PI3K), and glycogen synthase kinase (GSK)-3α. Upon TLR activation, phosphorylated forms of PI3K and GSK3α were detected in the mitochondria, and the mitochondrial membrane potential was impaired in sperm. In addition, mitochondrial ATP levels were decreased after TLR agonist stimulation. Furthermore, blocking PI3K or GSK3α activation abrogated these effects and reversed the TLR-induced reduction in sperm motility. These results identify a previously unrecognized TLR signalling pathway that leads to dysfunctional sperm mitochondria, which reduce sperm motility. Our study reveals a novel mechanism by which pathogenic infection affects sperm motility and possibly leads to infertility.
•TLR agonists can affect human and mice sperm motility.•TLR signalling inhibits sperm motility in a MyD88/PI3K/GSK3α-dependent manner.•TLR signalling leads to reduced ATP levels in sperm, accompanied by impaired mitochondrial function.
Long non-coding RNAs (lncRNAs) are important biological factors that contribute to the initiation and progression of different types of cancer, including gastric, bladder and colorectal cancer. Small ...nucleolar RNA host gene 3 (SNHG3) has been implicated in prostate cancer (PCa) progression. However, the expression pattern and function of SNHG3 in PCa remain unclear, impeding the development of novel treatment strategies for this cancer. The present study aimed to investigate a combination of molecular and biochemical approaches to determine the role of SNHG3 in patients at different stages of disease, and elucidate the pathway by which SNHG3 affects PCa progression. A Cell Counting Kit-8 assay was used to assess cell proliferation. Transwell assays were used to analyze cell migration and invasion. Reverse transcription-quantitative PCR and western blotting were used to evaluate the expression levels of RNAs and proteins, respectively. The results demonstrated that SNHG3 expression was upregulated in PCa tissues downloaded from The Cancer Genome Atlas database, which was associated with poor prognosis. Furthermore, cell proliferation, migration and invasion were significantly inhibited following SNHG3 knockdown in vitro, the effects of which were reversed following overexpression of SNHG3 in PCa cells. Bioinformatic analysis revealed that microRNA (miRNA/miR)-1827 was a downstream target of SNHG3. The direct interaction between SNHG3 and miR-1827 was validated via the dual-luciferase reporter and RNA immunoprecipitation assays. Pearson's correlation analysis demonstrated that SNHG3 expression was negatively correlated with miR-1827 expression at different stages of PCa. Furthermore, rescue assays indicated that cotransfection with small interfering-SNHG3 and miR-1827 inhibitor reversed the effects of SNHG3 knockdown on cell proliferation, migration and invasion. In addition, SNHG3 knockdown in vivo suppressed tumor growth. Notably, lncRNA SNHG3 promoted PCa progression through miR-1827 via the Wnt/AKT/mTOR pathway. Taken together, the results of the present study suggest that SNHG3 promotes PCa progression by sponging miR-1827, indicating that SNHG3 may be a promising diagnostic and therapeutic target of PCa. Key words: prostate cancer, long non-coding RNA, sponge, microRNA, cancer progression