Differential responses of the phyllosphere abundant and rare microbes of Eucommia ulmoides to phytohormones.

Phyllosphere microbiota play a crucial role in plant productivity and adaptation, and the abundant and rare microbial taxa often possess distinct characteristics and ecological functions. However, it is unclear whether the different subcommunities of phyllosphere microbiota respond variably to the factors that influence their formation, which limits the understanding of community assembly. The effects of two phytohormones, namely, indole-3-acetic acid (IAA) and N6-(delta 2-isopentenyl)-adenine (IP), on the phyllosphere microbial subcommunities of Eucommia ulmoides were investigated using potted experiments. The results demonstrated that the phytohormones induced significant variations in the composition, diversity, and function of the abundant microbial subcommunity in the phyllosphere of E. ulmoides, however, their effects on the rare subcommunity were negligible, and their effects on the moderate subcommunity were between those of the abundant and rare taxa. The phytohormones also induced significant alterations in the phenotypic and physiological properties of E. ulmoides, which indirectly affected the phyllosphere microbial community. Leaf thickness and average leaf area were the main phenotypic variables that affected the composition of the phyllosphere microbial community. The total alkaloid content and activity of superoxide dismutase (SOD) were the main physiological variables that affected the composition of the phyllosphere microbial community. The phenotypic and physiological indices of E. ulmoides explained the variations in the phyllosphere microbial subcommunities in descending order: abundant > moderate > rare taxa. These variables explained a significant proportion of the variations in the abundant taxa, and an insignificant proportion of the variations in the rare taxa. This study improves our understanding of the assembly of the phyllosphere microbiota, which provides important theoretical knowledge for future sustainable agriculture and forestry management based on the precise regulation of phyllosphere microbiota.

Advancements in inhibitors of crucial enzymes in the cysteine biosynthetic pathway: Serine acetyltransferase and O-acetylserine sulfhydrylase.

Infectious diseases have been jeopardized problem that threaten public health over a long period of time. The growing prevalence of drug-resistant pathogens and infectious cases have led to a decrease in the number of effective antibiotics, which highlights the urgent need for the development of new antibacterial agents. Serine acetyltransferase (SAT), also known as CysE in certain bacterial species, and O-acetylserine sulfhydrylase (OASS), also known as CysK in select bacteria, are indispensable enzymes within the cysteine biosynthesis pathway of various pathogenic microorganisms. These enzymes play a crucial role in the survival of these pathogens, making SAT and OASS promising targets for the development of novel anti-infective agents. In this comprehensive review, we present an introduction to the structure and function of SAT and OASS, along with an overview of existing inhibitors for SAT and OASS as potential antibacterial agents. Our primary focus is on elucidating the inhibitory activities, structure-activity relationships, and mechanisms of action of these inhibitors. Through this exploration, we aim to provide insights into promising strategies and prospects in the development of antibacterial agents that target these essential enzymes.

Knowledge of Alzheimer's disease and associated factors among adults in Zhuhai, China: a cross-sectional analysis.

BACKGROUND: This study aimed to assess the public knowledge regarding Alzheimer's Disease (AD) in Zhuhai, China, focusing on identifying knowledge gaps and the influence of demographic and health factors. METHODS: A cross-sectional study was conducted in Zhuhai, China, from October to November 2022. A total of 1986 residents from 18 communities were selected employing stratified multi-stage equi-proportional sampling. Questionnaires covering general information and the Alzheimer's Disease Knowledge Scale (ADKS) were investigated face-to-face. Ordinal multiclass logistic regression was applied to assess the relationship between AD awareness and demographic and health characteristics. RESULTS: The average ADKS score was 18.5 (SD = 3.36) in Zhuhai. The lowest awareness rates were observed in the "Symptoms" and "Caregiving" subdomains of ADKS, with rates of 51.01% and 43.78%, respectively. The correct rates for the 30 ADKS questions ranged from 16.62 to 92.6%, showing a bimodal pattern with clusters around 80% and 20%. Women (OR = 1.203, 95% CI: 1.009-1.435), individuals aged 60 years or older (OR = 2.073, 95% CI: 1.467-2.932), those living in urban areas (OR = 1.361, 95% CI: 1.117-1.662), higher average monthly household income per capita (OR = 1.641, 95% CI: 1.297-2.082), and without any neurological or mental disorders (OR = 1.810, 95% CI: 1.323-2.478) were more likely to have higher levels of awareness about Alzheimer's disease. CONCLUSIONS: Adults in Zhuhai show a limited knowledge of AD, particularly in the 'Symptoms' and 'Caregiving' subdomains. Upcoming health campaigns must focus on bridging the knowledge gaps in different subdomains of AD, especially among subgroups with lower awareness, as identified in our study.

Antimicrobial peptide immobilization on catechol-functionalized PCL/alginate wet-spun fibers to combat surgical site infection.

Surgical site infection (SSI) caused by pathogenic bacteria leads to delayed wound healing and extended hospitalization. Inappropriate uses of antibiotics have caused a surge in SSI and common antibiotics are proving to be ineffective against SSI. Antimicrobial peptides (AMPs) can be a potential solution to prevent SSI because of their broad spectrum of antimicrobial activities. In this study, naturally sourced AMPs were studied along with microfibers, fabricated by a novel wet-spinning method using sodium alginate and polycaprolactone. Afterward, fibers were functionalized by the catechol groups of dopamine immobilizing nucleophilic AMPs on the surface. Conjugation between PCL and alginate resulted in fibers with smooth surfaces improving their mechanical strength via hydrogen bonds. Having an average diameter of 220 µm, the mechanical properties of the fiber complied with USP standards for suture size 3-0. Engineered microfibers were able to hinder the growth of Proteus spp., a pathogenic bacterium for at least 60 hours whereas antibiotic ceftazidime failed. When subjected to a linear incisional wound model study, accelerated healing was observed when the wound was closed using the engineered fiber compared to Vicryl. The microfibers promoted faster re-epithelialization compared to Vicryl proving their higher wound healing capacity.

The First Discovery of Marine Polyoxygenated Cembranolides as Potential Agents for the Treatment of Ulcerative Colitis.

Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure-activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.

Fabrication of sea urchin shaped polyaniline-modified magnetic microporous organic network for efficient extraction of non-steroidal anti-inflammatory drugs from animal-derived food samples.

In this work, a novel polyaniline-modified magnetic microporous organic network (MMON-PANI) composite was fabricated for effective magnetic solid phase extraction (MSPE) of five typical nonsteroidal anti-inflammatory drugs (NSAIDs) from animal-derived food samples before high performance liquid chromatography (HPLC) detection. The core-shell sea urchin shaped MMON-PANI integrates the merits of Fe3O4, MON, and PANI, exhibiting large specific surface area, rapid magnetic responsiveness, good stability, and multiple binding sites to NSAIDs. Convenient and effective extraction of trace NSAIDs from chicken, beef and pork samples is realized on MMON-PANI via the synergetic π-π, hydrogen bonding, hydrophobic, and electrostatic interactions. Under optimal conditions, the MMON-PANI-MSPE-HPLC-UV method exhibits wide linear ranges (0.2-1000 µg L-1), low limits of detection (0.07-1.7 µg L-1), good precisions (intraday and inter-day RSDs < 5.4 %, n = 3), large enrichment factors (98.6-99.9), and less adsorbent consumption (3 mg). The extraction mechanism and selectivity of MMON-PANI are also evaluated in detail. This work proves the incorporation of PANI onto MMON is an efficient way to promote NSAIDs enrichment and provides a new strategy to synthesize multifunctional MON-based composites in sample pretreatment.

[Discussion on the effects of acupuncture-medication combination].

This article summarizes and discusses the collaborative effects of acupuncture and medication in treatment, including four aspects, named "acupuncture synergizing the effects of medication", "medication advancing the effects of acupuncture", "coordination of acupuncture and medication", and "antagonism of acupuncture and medication". Regarding "acupuncture synergizing the effects of medication", the actions of acupuncture are predominant, which affects the absorption and metabolism of drugs in the body, increases drug concentration in blood, enhances the targeting effect of drugs, guides meridian tropism, alleviates the drug dose and adverse reactions, avoids the first pass effect and accelerates the drug bioavailability. As for "medication advancing the effects of acupuncture", the synergistic effect of acupuncture is obtained by medication, besides, the medication itself may supplement the drug property to the needles during acupuncture pretreatment so as to increase the therapeutic effect. In terms of "coordination of acupuncture and medication", and "antagonism of acupuncture and medication", there are the underlying co-effects of acupuncture and medication in the body, and the action targets may be same or different between them, thus, it needs to be further explored.

METTL3-mediated NDUFB5 m6A modification promotes cell migration and mitochondrial respiration to promote the wound healing of diabetic foot ulcer.

BACKGROUND: Diabetic foot ulcer (DFU) is the most devastating complication of diabetes mellitus (DM) and plays a major role in disability and death in DM patients. NADH: ubiquinone oxidoreductase subunit B5 (NDUFB5) plays an important role in maintaining mitochondrial respiration, but whether it is involved in regulating the progression of advanced glycation end products (AGEs)-mediated DFU is still unclear. METHODS: Firstly, the role of AGEs on cell viability, migration, and mitochondrial respiration in human umbilical vein endothelial cells (HUVECs) was explored in vitro. Next, NDUFB5 expression was detected in human samples and AGEs-treated HUVECs, and NDUFB5's effect on AGEs-induced HUVECs injury and skin wound in diabetic mice was further clarified. In addition, the role of m6A modification mediated by methyltransferase-like 3 (METTL3) in regulating NDUFB5 expression and AGEs-induced HUVECs injury was investigated. RESULTS: NDUFB5 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs, whereas mitochondrial fusion promoter M1 facilitated cell viability, migration, and mitochondrial oxiadative respiration in NDUFB5 knockdown HUVECs. Meanwhile, NDUFB5 promotes skin wound healing in diabetic mice. Besides, METTL3-mediated m6A modification and insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) enhanced NDUFB5 expression in HUVECs. Furthermore, METTL3 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs by increasing NDUFB5. CONCLUSION: METTL3-mediated NDUFB5 m6A modification inhibits AGEs-induced cell injury in HUVECs. METTL3 and NDUFB5 might serve as potential targets for DFU therapy in the future.

[Progress in Lymphangiogenesis and Lymphatic Metastasis of Thyroid Carcinoma].

Thyroid carcinoma is a common endocrine malignancy,with most cases being indolent.Lymphatic metastasis as a representative metastasis type defines the clinical stage and prognosis of thyroid carcinoma.The mechanism of lymphatic metastasis in malignancies has been a research hotspot for years,and certain progress being achieved.This article reviews the molecular markers of lymphatic vessels and their application in diagnosis and treatment of neoplasms,the mechanism and role of lymphangiogenesis in lymphatic metastasis,the tracing methods for sentinel lymph nodes by lymphatic drainage,and the use of ultrasound in cervical lymph node metastasis of thyroid carcinoma.Especially,this paper details the application of conventional ultrasound,transvenous contrast-enhanced ultrasound,and trans-lymphatic contrast-enhanced ultrasound in cervical lymph node metastasis of thyroid carcinoma.

[Diagnostic Value of Ultrasound for Thyroid Nodules With a Spoke-Wheel Blood Flow Pattern].

Objective To explore the diagnostic value of ultrasound for thyroid nodules with a spoke-wheel blood flow pattern.Methods The clinical data of the patients with thyroid nodules presenting a spoke-wheel blood flow pattern examined by ultrasound were collected,and the gray-scale ultrasound features of the nodules were recorded.The diagnostic performance of the Thyroid Imaging Reporting and Data System by American College of Radiology (ACR TI-RADS),Chinese Thyroid Imaging Reporting and Data System (C-TIRADS),and combined specific indicators for the thyroid nodules with a spoke-wheel blood flow pattern was evaluated by comparison with the pathological results,which was regarded as the gold standard.Results A total of 64 patients with thyroid nodules were finally included,including 47 patients with malignant nodules and 17 patients with benign nodules.In addition to the general ultrasound features,central scar mostly appeared in malignant nodules (χ2=5.968,P=0.015),while central coarse calcification was more common in benign nodules (χ2=10.899,P=0.001).After the combination of central scar and central gross calcification,the diagnostic performance of ACR TI-RADS and C-TIRADS was improved (both P<0.001).Conclusions When the thyroid nodule shows a spoke-wheel blood flow pattern,one should be cautious of the possibility of malignancy.Combining central scar and central coarse calcification can improve the accuracy of ultrasonic diagnosis.

How to update esophageal masses imaging using literature review (MRI and CT features).

MRI offers new opportunities for detailed visualization of the different layers of the esophageal wall, as well as early detection and accurate characterization of esophageal lesions. Staging of esophageal tumors including extramural extent of disease, and status of the adjacent organ can also be performed by MRI with higher accuracy compared to other imaging modalities including CT and esophageal endoscopy. Although MDCT appears to be the primary imaging modality that is indicated for preoperative staging of esophageal cancer to assess tumor resectability, MDCT is considered less accurate in T staging. This review aims to update radiologists about emerging imaging techniques and the imaging features of various esophageal masses, emphasizing the imaging features that differentiate between esophageal masses, demonstrating the critical role of MRI in esophageal masses. CRITICAL RELEVANCE STATEMENT: MRI features may help differentiate mucosal high-grade neoplasia from early invasive squamous cell cancer of the esophagus, also esophageal GISTs from leiomyomas, and esophageal malignant melanoma has typical MR features. KEY POINTS: MRI can accurately visualize different layers of the esophagus potentially has a role in T staging. MR may accurately delineate esophageal fistulae, especially small mediastinal fistulae. MRI features of various esophageal masses are helpful in the differentiation.

Impact of genomic and epigenomic alterations of multigene on a multicancer pedigree.

BACKGROUND: Germline mutations have been identified in a small number of hereditary cancers, but the genetic predisposition for many familial cancers remains to be elucidated. METHODS: This study identified a Chinese pedigree that presented different cancers (breast cancer, BRCA; adenocarcinoma of the esophagogastric junction, AEG; and B-cell acute lymphoblastic leukemia, B-ALL) in each of the three generations. Whole-genome sequencing and whole-exome sequencing were performed on peripheral blood or bone marrow and cancer biopsy samples. Whole-genome bisulfite sequencing was conducted on the monozygotic twin brothers, one of whom developed B-ALL. RESULTS: According to the ACMG guidelines, bioinformatic analysis of the genome sequencing revealed 20 germline mutations, particularly mutations in the DNAH11 (c.9463G > A) and CFH (c.2314G > A) genes that were documented in the COSMIC database and validated by Sanger sequencing. Forty-one common somatic mutated genes were identified in the cancer samples, displaying the same type of single nucleotide substitution Signature 5. Meanwhile, hypomethylation of PLEK2, MRAS, and RXRA as well as hypermethylation of CpG island associated with WT1 was shown in the twin with B-ALL. CONCLUSIONS: These findings reveal genomic alterations in a pedigree with multiple cancers. Mutations found in the DNAH11, CFH genes, and other genes predispose to malignancies in this family. Dysregulated methylation of WT1, PLEK2, MRAS, and RXRA in the twin with B-ALL increases cancer susceptibility. The similarity of the somatic genetic changes among the three cancers indicates a hereditary impact on the pedigree. These familial cancers with germline and somatic mutations, as well as epigenomic alterations, represent a common molecular basis for many multiple cancer pedigrees.

NF2 regulates IP3R-mediated Ca2+ signal and apoptosis in meningiomas.

Meningiomas are the most common primary intracranial tumors and account for nearly 30% of all nervous system tumors. Approximately half of meningioma patients exhibit neurofibromin 2 (NF2) gene inactivation. Here, NF2 was shown to interact with the endoplasmic reticulum (ER) calcium (Ca2+) channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in IOMM-Lee, a high-grade malignant meningioma cell line, and the F1 subdomain of NF2 plays a critical role in this interaction. Functional assays indicated that NF2 promotes the phosphorylation of IP3R (Ser 1756) and IP3R-mediated endoplasmic reticulum (ER) Ca2+ release by binding to IP3R1, which results in Ca2+-dependent apoptosis. Knockout of NF2 decreased Ca2+ release and promoted resistance to apoptosis, which was rescued by wild-type NF2 overexpression but not by F1 subdomain deletion truncation overexpression. The effects of NF2 defects on the development of tumors were further studied in mouse models. The decreased expression level of NF2 caused by NF2 gene knockout or mutation affects the activity of the IP3R channel, which reduces Ca2+-dependent apoptosis, thereby promoting the development of tumors. We elucidated the interaction patterns of NF2 and IP3R1, revealed the molecular mechanism through which NF2 regulates IP3R1-mediated Ca2+ release, and elucidated the new pathogenic mechanism of meningioma-related NF2 variants. Our study broadens the current understanding of the biological function of NF2 and provides ideas for drug screening of NF2-associated meningioma.

MiPRIME: an integrated and intelligent platform for mining primer and probe sequences of microbial species.

MOTIVATION: Accurately detecting pathogenic microorganisms requires effective primers and probe designs. Literature-derived primers are a valuable resource as they have been tested and proven effective in previous research. However, manually mining primers from published texts is time-consuming and limited in species scop. RESULTS: To address these challenges, we have developed MiPRIME, a real-time Microbial Primer Mining platform for primer/probe sequences extraction of pathogenic microorganisms with three highlights: (i) comprehensive integration. Covering >40 million articles and 548 942 organisms, the platform enables high-frequency microbial gene discovery from a global perspective, facilitating user-defined primer design and advancing microbial research. (ii) Using a BioBERT-based text mining model with 98.02% accuracy, greatly reducing information processing time. (iii) Using a primer ranking score, PRscore, for intelligent recommendation of species-specific primers. Overall, MiPRIME is a practical tool for primer mining in the pan-microbial field, saving time and cost of trial-and-error experiments. AVAILABILITY AND IMPLEMENTATION: The web is available at {{https://www.ai-bt.com}}.

YAP inhibits NF-κB signaling and ccRCC growth by opposing p65-ZHX2 cooperativity.

Hippo pathway functions as a tumor suppressor pathway by inhibiting the oncogenic potential of pathway effectors YAP/TAZ. However, YAP can also function as a context-dependent tumor suppressor in several types of cancer including clear cell renal cell carcinomas (ccRCC). Here we show that YAP blocks NF-κB signaling in ccRCC to inhibit cancer cell growth. Mechanistically, YAP inhibits the expression of ZHX2, a critical p65 co-factor in ccRCC. Furthermore, YAP competes with ZHX2 for binding to p65. Consequently, elevated nuclear YAP blocks the cooperativity between ZHX2 and p65, leading to diminished NF-κB target gene expression. Pharmacological inhibition of Hippo/MST1/2 blocked NF-κB transcriptional program and suppressed ccRCC cancer cell growth, which can be rescued by ZHX2/p65 overexpression. Our study uncovers a novel crosstalk between the Hippo and NF-κB pathways and its involvement in ccRCC growth inhibition, suggesting that targeting the Hippo pathway may provide a therapeutical opportunity for ccRCC treatment.

Genetic Engineering for Enhancing Sugarcane Tolerance to Biotic and Abiotic Stresses.

Sugarcane, a vital cash crop, contributes significantly to the world's sugar supply and raw materials for biofuel production, playing a significant role in the global sugar industry. However, sustainable productivity is severely hampered by biotic and abiotic stressors. Genetic engineering has been used to transfer useful genes into sugarcane plants to improve desirable traits and has emerged as a basic and applied research method to maintain growth and productivity under different adverse environmental conditions. However, the use of transgenic approaches remains contentious and requires rigorous experimental methods to address biosafety challenges. Clustered regularly interspaced short palindromic repeat (CRISPR) mediated genome editing technology is growing rapidly and may revolutionize sugarcane production. This review aims to explore innovative genetic engineering techniques and their successful application in developing sugarcane cultivars with enhanced resistance to biotic and abiotic stresses to produce superior sugarcane cultivars.

Neurofibromin 2 modulates Mammalian Ste2-like kinases1/2 and large tumor suppressor gene1 expression in A549 lung cancer cell line.

AIM: To explore the impact of up- or down-regulation of Neurofibromin 2 (NF2) on the expression of downstream Hippo pathway genes, large tumor suppressor gene1 (LATS1), and phosphorylation of Mammalian Ste2-like kinases1/2 (MST1/2), in lung cancer cells. METHODS: A549 lung cancer cells were used. The NF2 was down-regulated by si-RNA interference and upregulated by lentiviral vector mediated overexpression. The LATS1 and MST1/2 expressions were evaluated by real-time PCR and western blot. RESULTS: Down-regulation of NF2 decreased LATS1 and MST1/2 level (P<0.05). Overexpression of NF2 increased LATS1 (P<0.05) and Mammalian Ste2-like kinases1 (MST1) (P<0.05), suggesting LATS1 and MST1 are modulated by NF2 in a lung cancer cell line. CONCLUSIONS: NF2 mediates the downstream LATS1 and MST1/2 expressions in a lung cancer cell line.

Modified TI-RADS Coupled with BRAFV600E Enhances Diagnostic Efficiency in Papillary Thyroid Carcinoma: Prospective Study.

Background: Thyroid disorders, relatively common diseases of the endocrine system, have risen gradually in recent years. Early detection and accurate diagnosis of thyroid cancer hold exceptional importance. This study aimed to determine the efficacy of a modified TI-RADS and BRAFV600E mutation testing for thyroid cancer (PTC) diagnosis. Methods: Ninety five thyroid nodules (48 benign and 47 malignant) from 81 patients were examined using Kwak Thyroid Imaging Reporting and Data System (TI-RADS) were subjected to shear wave elasticity (SWE), BRAFV600E genotyping and fine needle aspiration (FNA) cytology. Results: The modified TI-RADS exhibited superior diagnostic accuracy compared to TI-RADS in differentiating benign nodules from malignant thyroid nodules. Moreover, the AUC of modified TI-RADS in conjunction with BRAFV600E was the highest at 95% CI (0.898-0.992, p=0.003), surpassing other diagnostic methods in enhanced sensitivity and maintaining high specificity. Conclusion: The diagnostic efficiency of this combination surpassed that of individual diagnostic methods.

Inhibition of fusarium graminearum growth and spore germination by a streptomyces amritsarensis strain capable of killing and growing on microcystis scum.

AIMS: Developing energy-saving and ecofriendly strategies for treating harvested Microcystis biomass. METHODS AND RESULTS: Streptomyces amritsarensis HG-16 was first reported to effectively kill various morphotypes of natural Microcystis colonies at very high cell densities. Concurrently, HG-16 grown on lysed Microcystis maintained its antagonistic activity against plant pathogenic fungus Fusarium graminearum. It could completely inhibit spore germination and destroy mycelial structure of F. graminearum. Transcriptomic analysis revealed that HG-16 attacked F. graminearum in a comprehensive way: interfering with replication, transcription, and translation processes, inhibiting primary metabolisms, hindering energy production and simultaneously destroying stress-resistant systems of F. graminearum. CONCLUSIONS: The findings of this study provide a sustainable and economical option for resource reclamation from Microcystis biomass: utilizing Microcystis slurry to propagate HG-16, which can subsequently be employed as a biocontrol agent for managing F. graminearum.