Holliday junction resolvase RuvC targets biofilm eDNA and confers plant resistance to vascular pathogens.

A biofilm lifestyle is critical for bacterial pathogens to colonize and protect themselves from host immunity and antimicrobial chemicals in plants and animals. The formation and regulation mechanisms of phytobacterial biofilm are still obscure. Here we found that the protein Ralstonia solanacearum resistance to ultraviolet C (RuvC) is highly abundant in biofilm and positively regulates pathogenicity by controlling systemic movement in tomato xylem. RuvC protein accumulates at the later stage of biofilm development and specifically targets Holliday junction (HJ)-like structures to disrupt the biofilm extracellular DNA (eDNA) lattice, thus facilitating biofilm dispersal. Recombinant RuvC protein can resolve extracellular HJ to prevent bacterial biofilm formation. Heterologous expression of R. solanacearum or Xanthomonas oryzae pv. oryzae RuvC with plant secretion signal in tomato or rice confers resistance to bacterial wilt or bacterial blight disease, respectively. Plant chloroplast-localized HJ resolvase monokaryotic chloroplast 1 (MOC1), which shares structural similarity with bacterial RuvC, shows a strong inhibitory effect on bacterial biofilm formation. Relocalization of SlMOC1 to apoplast in tomato roots leads to increased resistance to bacterial wilt. Our novel finding reveals a critical pathogenesis mechanism of R. solanacearum and provides an efficient biotechnology strategy to improve plant resistance to bacterial vascular disease.

Synergistic Pd/Ni Dual-Catalyzed Cross-Coupling of Azaaryl Acetates with gem-Difluorinated Cyclopropanes.

We herein report the development of a novel Pd/Ni dual-catalyzed ring-opening functionalization of gem-difluorinated cyclopropanes (gem-F2CPs) with azaaryl acetates. This bimetallic catalytic strategy streamlines the diversity-oriented synthesis (DOS) of α-quaternary 2-fluoroallylic azaaryl acetates with features of a broad scope and excellent functional group tolerance, which enables the efficient late-stage transformation of natural product-derived gem-F2CPs. The resulting α-quaternary azaaryl acetates could serve as a valuable platform to prepare other different fluoroallylic azaaryl scaffolds.

Comparative study of robotic-assisted single-incision-plus-one port and single-incision laparoscopic choledochal cyst excision.

Objective: To compare the efficacy of robotic-assisted single-incision-plus-one-port laparoscopic choledochal cyst excision (R-SILC + 1) and single-incision laparoscopic choledochal cyst (SILC) in treating pediatric choledochal cyst (CDC). Methods: We retrospectively analyzed the clinical data of patients diagnosed with CDC in our hospital from June 2021 to October 2023. Among them, patients underwent either R-SILC + 1 or SILC procedures. Demographic parameters, operative details, and postoperative outcomes were studied. Results: A total of forty-nine patients were included, with 23 children undergoing R-SILC + 1 and 26 children undergoing SILC. There were no statistically significant differences in demographic data, postoperative pain scores, and postoperative complication rates between the two groups (all p > 0.05). Compared with the SILC group, the R-SILC + 1 group demonstrated less intraoperative bleeding volume (10.4 ± 3.6 vs. 15.0 ± 3.6 ml, p < 0.05), a shorter indwelling time of the abdominal drainage tube [5(5,6) vs. 7(5.8,8.3) d, p < 0.05], a shorter postoperative fasting time [4(3,4) vs. 6(5,7) d, p < 0.05], and a shorter postoperative discharge time [6(6,7) vs. 8(6,11) d, p < 0.05]. However, the R-SILC + 1 group had a longer operation time [388(295,415) vs. 341(255.8,375.2) min, p < 0.05] and higher hospitalization cost (7.9 ± 0.4 vs. 3.2 ± 0.3 ten thousand, p < 0.05). Conclusion: Compared with the SILC group, the R-SILC + 1 group demonstrated clear advantages in treating pediatric CDC, but it is associated with a prolonged learning curve and operation time, and high costs. With improvements in physician experience and technological advancements, its potential will be further unleashed.

Pharmacokinetics, Pharmacodynamics, and Safety of Intravenous Efgartigimod and Subcutaneous Efgartigimod PH20 in Healthy Chinese Participants.

BACKGROUND: Efgartigimod, a human immunoglobulin G (IgG)1-derived Fc fragment targeting the neonatal Fc receptor, has been developed into intravenous (IV) and subcutaneous (SC) formulations for treating generalized myasthenia gravis (gMG) and other autoimmune diseases. Data in the Chinese population were not available to date, and while both formulations have been approved in the USA, the EU, Japan and China for the treatment of gMG. OBJECTIVE: We present the pharmacokinetic, pharmacodynamic, and safety of IV and SC PH20 efgartigimod in healthy Chinese participants. METHODS: In two independent, double-blinded, placebo-controlled, phase I studies of the IV and SC formulations of efgartigimod, healthy Chinese adults were randomized 3:1 to receive active treatment or matching placebo once every 7 days for four doses. Primary endpoints were pharmacokinetic parameters. RESULTS: After the fourth IV infusion, a mean maximum observed concentration (Cmax) of 194 µg/mL was reached at the end of the 1 h infusion; the mean area under concentration-time curve from time zero to 168 h (AUC0-168h) was 5300 µg × h/mL. After the fourth SC injection, a mean Cmax of 42.1 µg/mL was achieved with a median Tmax of 47.74 h; the mean AUC0-168h was 4790 µg × h/mL. Maximal mean reductions from baseline in total IgG levels were reached approximately 24 days after the first dose (60.7%, IV formulation; 66.4%, SC formulation). Treatment-related adverse events (TRAEs) were reported in seven (58.3%) participants receiving SC efgartigimod, mostly injection-site reactions. No TRAEs or AEs of special interest were reported in the IV study. CONCLUSIONS: The efgartigimod IV and SC pharmacokinetic, pharmacodynamic, and safety profiles in Chinese participants were similar to the known profiles in non-Chinese participants. Both formulations effectively reduced total IgG levels by a similar percentage. CLINICAL TRIAL REGISTRATION: CTR20211952 and CTR20211805.

Cytidine Deaminase Enhances Liver Cancer Invasion by Modulating Epithelial-Mesenchymal Transition via NFκB Signaling.

BACKGROUND: Cancer metastasis is the leading cause of cancer-related deaths, underscoring the importance of understanding its underlying mechanisms. Hepatocellular carcinoma (HCC), a highly malignant type of cancer, was selected as our research model. MATERIAL AND METHODS: We aimed to develop high-metastatic cell lines using in vitro and in vivo selection strategies and identify critical metastasis-related genes through microarray analyses by comparing them with parental cells. RESULTS: Our results showed that the high-metastatic cell lines exhibited significantly stronger invasion abilities than parental cells. Microarray analyses identified cytidine deaminase (CDA), a gene associated with systemic chemotherapy resistance, as one of the overexpressed genes in the high-metastatic cells. Data analysis from The Cancer Genome Atlas Program revealed that while CDA is downregulated in HCC, patients with high CDA expression tend to have poorer prognoses. Cell models confirmed that CDA overexpression enhances cell migration and invasion, whereas CDA knockdown inhibits these abilities. Investigating the key molecules involved in the epithelial-mesenchymal transition (EMT), we found that CDA overexpression increases the expression of fascin, N-cadherin, ß-catenin, and snail while decreasing E-cadherin expression. Conversely, CDA knockdown produced opposite results. Additionally, we discovered that CDA regulates NF-κB signaling, which controls the expression of N-cadherin, thereby promoting the invasion capability of HCC cells. CONCLUSIONS: We isolated highly metastatic cells and identified potential HCC metastasis-related genes. CDA promotes cell invasion by regulating EMT through the NF-κB pathway. Future studies are warranted to explore the potential of CDA as a biomarker for prognosis and therapeutic decision-making.

Pseudogene: Relevant or Irrelevant?

With the advancement of high-throughput technologies, the pivotal role of non-coding RNA (ncRNA) as a master regulator of various biological functions has become increasingly apparent. Historically considered non-functional and labeled as "junk DNA," pseudogenes can be transcribed into RNA, indicating a potential role similar to ncRNAs. Recent research suggests that some pseudogenes can encode functional peptides or proteins. A growing body of evidence has revealed that pseudogenes and their derived functional molecules are involved in various biological processes and can serve as prognostic markers in cancers. This review comprehensively summarizes and discusses the current understanding of the functional roles of pseudogenes and their derived molecules in biological functions.

A 1024-Channel Simultaneous Electrophysiological and Electrochemical Neural Recording System with In-Pixel Digitization and Crosstalk Compensation.

Simultaneous electrophysiological and chemical recording allows for multi-modal neural instrumentation and provides insights into chemical synapses and ion channels across the cell membrane. However, intermodal interference can hinder highly synchronized recording in large-scale systems with high temporal and spatial resolution. In this work, we propose a 1024-channel lab-on-CMOS system for dual-modal neural recording with in-pixel digitization and interference suppression. A foreground calibration scheme with tunable capacitance is implemented in-pixel to compensate for the crosstalk between electrical and chemical recording. Active pixels for both electrical and chemical modalities are designed based on a pulse width modulation (PWM) analog-to-digital conversion scheme. CMOS-compatible post-processing is implemented to realize in-pixel electrodes and chemical sensing membranes. The prototype, implemented in a 180nm CMOS technology, occupies a total area of 33mm2 with 1024 pixels, and each unit pixel includes one electrical recording site and two chemical recording sites, with dimensions of 150µm×130 µm. The total system power consumption is 19.68mW at a frame rate of 9k and 3k for electrical and chemical imaging respectively. The in-vitro experiment demonstrated the concurrent high density electrophysilogical and electrochemical recording with sub millisecond temporal resolution.

Controlling functional homeostasis of ileal resident macrophages by vitamin B12 during steady state and Salmonella infection in mice.

Dietary micronutrients, particularly vitamin B12 (VB12), profoundly influence the physiological maintenance and function of intestinal cells. However, it is still unclear whether VB12 modulates the transcriptional and metabolic programming of ileal macrophages (iMacs), thereby contributing to intestinal homeostasis. Using multiomic approaches, we demonstrated that VB12 primarily supports the cell cycle activity and mitochondrial metabolism of iMacs, resulting in increased cell frequency compared to VB12 deficiency. VB12 also retained the ability to promote maintenance and metabolic regulation of iMacs during intestinal infection with Salmonella Typhimurium (STm). On the contrary, depletion of iMacs by inhibiting CSF1R signaling significantly increased host susceptibility to STm and prevented VB12-mediated pathogen reduction. These results thus suggest that regulation of VB12-dependent iMacs critically controls STm expansion, which may be of new relevance to advance our understanding of this vitamin and to strategically formulate sustainable therapeutic nutritional regimens that improve human gut health.

Exploring the Biosynthetic Potential of Tistrella Species for Producing Didemnin Antitumor Agents.

Didemnins are a class of cyclic depsipeptides derived from sea tunicates that exhibit potent anticancer, antiviral, and immunosuppressive properties. Although certain Tistrella species can produce didemnins, their complete biosynthetic potential remains largely unexplored. In this study, we utilize feature-based molecular networking to analyze the metabolomics of Tistrella mobilis and Tistrella bauzanensis, focusing on the production of didemnin natural products. In addition to didemnin B, we identify nordidemnin B and [hysp2]didemnin B, as well as several minor didemnin analogs. Heterologous expression of the didemnin biosynthetic gene cluster in a Streptomyces host results in the production of only didemnin B and nordidemnin B in limited quantities. Isotope-labeling studies reveal that the substrate promiscuity of the adenylation domains during biosynthesis leads to the accumulation of nordidemnin B and [hysp2]didemnin B. Additionally, precursor-directed biosynthesis is applied to generate eight novel didemnin derivatives by supplementing the culture with structurally related amino acids. Furthermore, we increased the titers of nordidemnin B and [hysp2]didemnin B by supplementing the fermentation medium with l-valine and l-isoleucine, respectively. Finally, both compounds undergo side-chain oxidation to enhance their biological activity, with their anticancer properties found to be as potent as plitidepsin.

Association between untreated caries and cariogenic bacteria in adolescents in Taiwan.

Background/purpose: There is a paucity of research focused on salivary bacteria analyzed through real-time polymerase chain reaction (qPCR) among adolescents. The current study determined the quantity of Streptococcus mutans (SM) and Lactobacillus (LB) in saliva obtained from Taiwanese adolescents and investigated the association between the oral bacteria and untreated dental caries. Materials and methods: This cross-sectional study recruited Taiwanese students aged 10-18. Saliva was collected using a Salivette kit and then analyzed through qPCR. The relative quantification values of SM and LB were coded based on mean fold ratios, with values > 2 coded as high and other values coded as low. Untreated dental caries was assessed through standard oral examinations. Univariate and multivariate logistic regression models were used to estimate the association between the levels of bacteria in the saliva of the study participants and the presence of untreated caries. Results: The study involved 421 adolescents. 56 (13.3%) had both SM and LB values of >2 and were coded as having high levels of bacteria, whereas the other 365 (86.7%) students were coded as having low levels. The multivariate logistic regression analysis revealed that adolescents who had high combined salivary SM and LB levels had an odds ratio of having untreated dental caries of 2.05 (95% CI = 1.09, 3.86, P = 0.027) compared with those who had low salivary SM and LB levels. Conclusion: The results of the present study indicate that salivary SM and LB levels are significantly associated with adolescents having untreated caries.

One-Pot Synthesis of Tannic Acid-Au Nanoparticles for the Colorimetric Determination of Hydrogen Peroxide and Glucose.

This study introduces a novel one-pot method employing tannic acid (TA) to synthesize stable gold nanoparticles (TA-AuNPs), which are characterized using transmission electron microscopy, X-ray powder diffraction, and Fourier transform infrared spectroscopy. We apply these TA-AuNPs in a newly developed colorimetric assay for hydrogen peroxide (H2O2) detection that utilizes the oxidation of iodide (I-) on TA-AuNPs, leading to a detectable yellow color change in the solution. The reaction kinetics are captured by the rate equation R = 0.217[KI]0.61[H2O2]0.69. The possible sensing mechanism was proposed through density functional theory calculations. At the optimum conditions, the proposed TA-AuNPs/I- system demonstrated a linear relationship between H2O2 concentration and absorbance intensity (λ = 350 nm) and achieved a limit of detection (LOD) of 7.33 µM. Furthermore, we expand the utility of this approach to glucose detection by integrating glucose oxidase into the system, resulting in a LOD of 10.0 µM. Application of this method to actual urine samples yielded spiked recovery rates ranging from 96.6-102.0% and relative standard deviations between 3.00-8.34%, underscoring its efficacy and potential for real-world bioanalytical challenges.

Characterization of an Environmentally Responsive Organic-Inorganic Hybrid Fe3O4/SiO2/PPy-c Core-Shell Nanocomposite with Magneto-Chromatic Ability for Synergistic Electrical Properties.

The aim of this study was to analyze the properties of a composite that incorporates carbon black and polypyrrole within an Fe3O4/SiO2 core-shell structure, synthesized using the Stöber method under high ultrasonic irradiation conditions (120 W) for Fe3O4/SiO2 nanocomposite. The Fe3O4/SiO2 core-shell indicates magnetochromatic behavior characterized by temperature-dependent coloration and magnetic alignment. Incorporating carbon black and polypyrrole at moderate temperature (5-15 °C) enhanced the electrical conductivity. The electrical resistivity ρ was 7.30 × 106 Ω·cm for Fe3O4, 3.19 × 108 Ω·cm for Fe3O4/SiO2, and 242.56 Ω·cm for Fe3O4/SiO2/PPy-c at room temperature. When it was performed at moderate temperature (5-15 °C), the ρ of the prepared Fe3O4/SiO2 and Fe3O4/SiO2/PPy-c nanocomposite was 1.08 × 108 and 0.00799 Ω·cm, respectively. Current-voltage measurements revealed a linear relationship, with butterfly shaped curves in the forward-bias region for all samples. The Fe3O4/SiO2/PPy-c nanocomposite's tunable synergistic electrical properties at moderate temperatures make it useful for environmental applications, electrical wiring, and circuitry.

Microfluidics in smart food safety.

The evolution of food safety practices is crucial in addressing the challenges posed by a growing global population and increasingly complex food supply chains. Traditional methods are often labor-intensive, time-consuming, and susceptible to human error. This chapter explores the transformative potential of integrating microfluidics into smart food safety protocols. Microfluidics, involving the manipulation of small fluid volumes within microscale channels, offers a sophisticated platform for developing miniaturized devices capable of complex tasks. Combined with sensors, actuators, big data analytics, artificial intelligence, and the Internet of Things, smart microfluidic systems enable real-time data acquisition, analysis, and decision-making. These systems enhance control, automation, and adaptability, making them ideal for detecting contaminants, pathogens, and chemical residues in food products. The chapter covers the fundamentals of microfluidics, its integration with smart technologies, and its applications in food safety, addressing the challenges and future directions in this field.

Construction of nomogram based on clinical factors for the risk prediction of postoperative complications in children with choledochal cyst.

Objective: The aim of the study was to develop a prediction nomogram based on clinical factors to assess the risk of postoperative complications in children with congenital choledochal cyst. Methods: The clinical data from 131 children who underwent choledochal cyst resection and Roux-en-Y hepaticojejunostomy in our hospital between January 2016 and December 2022 were retrospectively analyzed. The general information, clinical symptoms, procedure, biochemical indicators, and imaging data were recorded. A prolonged hospital stay induced by postoperative complications or a follow-up over 6 months was assessed as the event outcome. A logistics regression analysis was performed to screen for risk factors with statistical significance in inducing postoperative complications. Then, with the dataset split into the training group and internal validation group, the nomogram for the prediction of postoperative complications was developed based on a computer algorithm. In addition, the receiver operating characteristic (ROC) curve and calibration curve were performed for nomogram verification. Results: Of 131 children, the multivariate logistics regression analysis suggested that age ≤2 years [odds ratio (OR) 0.93; 95% confidence interval (CI) 0.15-5.65; p = 0.938], Todani classification type 1 (OR 36.58; 95% CI 4.14-871.74; p = 0.005), cyst wall thickness >0.4 cm (OR 10.82; 95% CI 2.88-49.13; p < 0.001), with chronic cholecystitis (OR 7.01; 95% CI 1.62-38.52; p = 0.014), and choledochal cyst diameter (OR 1.01; 95% CI 0.99-1.03; p = 0.370) were predictors associated with the postoperative complications of choledochal cysts. The data were randomly divided into the training group (n = 92) and internal validation group (n = 39) to build the prediction nomogram including the appeal factors. The accuracy and discrimination of the model were evaluated using a ROC curve and calibration curve. The results showed that the nomogram area under the ROC curve [area under the curve (AUC) = 0.894; 95% CI 0.822-0.966; p < 0.001], validation (AUC = 0.844; 95% CI 0.804-0.952; p < 0.001), and Brier = 0.120 (95% CI 0.077-0.163p; p < 0.001) were indicative of the good stability and calibration of the predictive nomogram. Conclusion: The prognosis of congenital choledochal cysts was associated with multiple aspects of clinical factors. Combined with the internal validation, the novel prediction nomogram was suitable for evaluating the individualized risk of postoperative complications of choledochal cysts. The prediction nomogram could provide a more accurate strategy of procedure and postoperative follow-up for children with choledochal cysts.

CCL16 is a pro-tumor chemokine that recruits monocytes and macrophages to promote hepatocellular carcinoma progression.

Intricate signaling cascades involving chemokines and their cognate receptors on neoplastic and immune constituents within tumor microenvironment have garnered substantial research interest. Our investigation delineates the contribution of Chemokine (C-C motif) ligand 16 (CCL16) to the clinico-pathological features and tumorigenesis of hepatocellular carcinoma (HCC). Analysis of 237 pairs of HCC specimens unraveled a significant association between CCL16 expression and vascular invasion, early-stage clinicopathological features, and diminished recurrence-free survival among HCC patients. Immunohistochemical (IHC) assays of the clinical HCC specimens indicated elevated CCL16 in tumorous versus normal hepatic tissues. Our in vivo experiments demonstrated CCL16 overexpression fostered tumor proliferation, whereas in vitro assays elucidated that CCL16-mediated chemotactic recruitment of monocytes and M2 macrophages was orchestrated via CCR1 and CCR5. In contrast to previous claims that CCL16 is physiologically irrelevant and has minimal affinity for its receptors (CCR1, CCR2, CCR5, CCR8), our findings unravel that inhibition of CCL16/CCR1 and CCL16/CCR5 interactions through receptor-specific antagonists markedly impeded CCL16-directed chemotaxis, migration, adhesion, and leukocyte recruitment. Moreover, CCL16-overexpression in HCCs significantly augmented levels of several cytokines implicated in tumor progression, namely IL-6, IL-10 and VEGFA. IHC analysis of CCL16-overexpressing xenografts elicited greatly enhanced levels of VEGFA and IL-6, while assessments of HCC specimens confirmed a positive correlation between CCL16 expression and IL-6 and VEGFA levels. Collectively, our study highlights oncogenic role of CCL16 in hepatocarcinogenesis and provides a foundational basis for novel therapeutic interventions targeting the CCL16/CCR1/CCR5 axis.

Identifying Acute Aortic Syndrome and Thoracic Aortic Aneurysm from Chest Radiography in the Emergency Department Using Convolutional Neural Network Models.

(1) Background: Identifying acute aortic syndrome (AAS) and thoracic aortic aneurysm (TAA) in busy emergency departments (EDs) is crucial due to their life-threatening nature, necessitating timely and accurate diagnosis. (2) Methods: This retrospective case-control study was conducted in the ED of three hospitals. Adult patients visiting the ED between 1 January 2010 and 1 January 2020 with a chief complaint of chest or back pain were enrolled in the study. The collected chest radiography (CXRs) data were divided into training (80%) and testing (20%) datasets. The training dataset was trained by four different convolutional neural network (CNN) models. (3) Results: A total of 1625 patients were enrolled in this study. The InceptionV3 model achieved the highest F1 score of 0.76. (4) Conclusions: Analysis of CXRs using a CNN-based model provides a novel tool for clinicians to interpret ED patients with chest pain and suspected AAS and TAA. The integration of such imaging tools into ED could be considered in the future to enhance the diagnostic workflow for clinically fatal diseases.

Predictive value of Vitamin D levels in pregnant women on gestational length and neonatal weight in China: a population-based retrospective study.

BACKGROUND: Vitamin D deficiency, a common occurrence among pregnant women, is an emerging public health concern worldwide. According to research, prenatal vitamin D deficiency is associated with various complications. This study assessed the vitamin D status of pregnant women in Yanbian, Jilin Province, as well as the correlation and predictive value of their vitamin D levels in relation to gestational length (weeks) and fetal weight, aiming to provide a basis for clinical diagnosis and treatment. METHODS: We conducted a population-based retrospective study involving 510 pregnant women from August 2019 to October 2022. Blood samples were collected at 16-20 weeks of gestation for the detection of serum vitamin D levels. Statistical analyses were performed using SPSS 28.0 and R 4.1.0 software. Multifactorial logistic regression analysis was employed to establish whether each variable was a risk factor for deliveries at ≤ 38 gestational weeks and low fetal weight. These results were used to construct a risk prediction model, and the model's predictive efficacy was evaluated. Results or differences with p < 0.05 were considered statistically significant. RESULTS: Multifactorial logistic regression analysis revealed that vitamin D ≤ 14.7 ng/mL(OR: 1.611; 95% CI: 1.120-2.318; P = 0.010), Bone Mineral Density (BMD) T-value ≤-1(OR: 1.540; 95%CI: 1.067-2.223; P = 0.021), and gestational hypertension(OR: 7.173; 95% CI: 1.482-34.724; P = 0.014) were the independent risk factors for deliveries at ≤ 38 gestational weeks. Additionally, vitamin D ≤ 14.7 ng/mL(OR: 1.610; 95%CI: 1.123-2.307; P = 0.009), BMD T-value ≤ -1(OR: 1.560; 95%CI: 1.085-2.243; P = 0.016), and gestational hypertension(OR: 4.262; 95% CI: 1.058-17.167; P = 0.041) were the independent risk factors for low fetal weight (< 3400 g). CONCLUSION: This study revealed that low vitamin D levels are an independent risk factor for a short gestational length and low fetal weight. Prenatal low BMD T-value and comorbid hypertensive disorders were also found to increase the risk of a short gestational length and low fetal weight.

Seven-Day Vonoprazan-Based Triple Therapy as First-Line Helicobacter pylori Treatment in Comparison With Extended Sequential Therapy: A Randomized Controlled Trial.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, has demonstrated greater potency and a longer duration of acid suppression when compared to the proton pump inhibitors. However, data regarding the comparison between vonoprazan-based triple therapy with standard treatment for first-line Helicobacter pylori treatment are limited. This study aimed to compare the efficacy between 7-day vonoprazan-based triple therapy with high-dose amoxicillin (VAC-7) and 14-day extended sequential therapy (S-14). MATERIALS AND METHODS: This was a single-center prospective randomized controlled trial following a noninferiority design. Subjects over 20 years old with confirmed H. pylori infection were enrolled prospectively from Fu Jen Catholic University Hospital. They were randomly assigned to the VAC-7 or S-14 group. The primary endpoint was the eradication rate in first-line treatment, evaluated by urea breath test, with noninferiority determined using the Farrington-Manning method. The secondary outcome included adverse effect rates and compliance, assessed through self-administered questionnaires. RESULTS: Between December 2021 and June 2023, a total of 628 patients were recruited. The eradication rates by per-protocol analysis and intention-to-treat analysis were 88.6%/81.8% for VAC-7 and 90.3%/81.4% for S-14, respectively. The VAC-7 was non-inferior to S-14 in terms of ITT analysis. Subjects experienced fewer incidences of nausea, anorexia, dizziness, fatigue, and any severe adverse events in the VAC-7 group. Compliance was higher in the VAC-7 group, with 94% taking all the pills correctly. CONCLUSIONS: Our findings supported the use of 7-day vonoprazan triple therapy with high-dose amoxicillin as the standard first-line treatment for H. pylori infection. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05371249.

Dynamics of Physiological Properties and Endophytic Fungal Communities in the Xylem of Aquilaria sinensis (Lour.) with Different Induction Times.

Xylem-associated fungus can secrete many secondary metabolites to help Aquilaria trees resist various stresses and play a crucial role in facilitating agarwood formation. However, the dynamics of endophytic fungi in Aquilaria sinensis xylem after artificial induction have not been fully elaborated. Endophytic fungi communities and xylem physio-biochemical properties were examined before and after induction with an inorganic salt solution, including four different times (pre-induction (0M), the third (3M), sixth (6M) and ninth (9M) month after induction treatment). The relationships between fungal diversity and physio-biochemical indices were evaluated. The results showed that superoxide dismutase (SOD) and peroxidase (POD) activities, malondialdehyde (MDA) and soluble sugar content first increased and then decreased with induction time, while starch was heavily consumed after induction treatment. Endophytic fungal diversity was significantly lower after induction treatment than before, but the species richness was promoted. Fungal ß-diversity was also clustered into four groups according to different times. Core species shifted from rare to dominant taxa with induction time, and growing species interactions in the network indicate a gradual complication of fungal community structure. Endophytic fungi diversity and potential functions were closely related to physicochemical indices that had less effect on the relative abundance of the dominant species. These findings help assess the regulatory mechanisms of microorganisms that expedite agarwood formation after artificial induction.