Metal-Organic Framework Based Mucoadhesive Nanodrugs for Multifunction Helicobacter Pylori Targeted Eradication, Inflammation Regulation and Gut Flora Protection.

The prevalence of drug-resistant bacteria presents a significant challenge to the antibiotic treatment of Helicobacter pylori (H. pylori), while traditional antimicrobial agents often suffer from shortcomings such as poor gastric retention, inadequate alleviation of inflammation, and significant adverse effects on the gut microbiota. Here, a selenized chitosan (CS-Se) modified bismuth-based metal-organic framework (Bi-MOF@CS-Se) nanodrug is reported that can target mucin through the charge interaction of the outer CS-Se layer to achieve mucosal adhesion and gastric retention. Additionally, the Bi-MOF@CS-Se can respond to gastric acid and pepsin degradation, and the exposed Bi-MOF exhibits excellent antibacterial properties against standard H. pylori as well as clinical antibiotic-resistant strains. Remarkably, the Bi-MOF@CS-Se effectively alleviates inflammation and excessive oxidative stress by regulating the expression of inflammatory factors and the production of reactive oxygen species (ROS), thereby exerting therapeutic effects against H. pylori infection. Importantly, this Bi-MOF@CS-Se nanodrug does not affect the homeostasis of gut microbiota, providing a promising strategy for efficient and safe treatment of H. pylori infection.

The role of immune cells in different stages of atherosclerosis.

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of immune cells in the intima of arteries. Experimental and clinical evidence shows that both innate and adaptive immunity orchestrate the progression of atherosclerosis. The heterogeneous nature of immune cells within atherosclerosis lesions is important. Studies utilizing high-dimensional mass spectrometry and single-cell RNA sequencing of leukocytes from atherosclerotic lesions show the diversity and adaptability of these immune cell subtypes. Their migration, compositional changes, phenotypic alterations, and adaptive responses are key features throughout atherosclerosis progression. Understanding how these immune cells and their subtypes affect atherogenesis would help to develop novel therapeutic approaches that control atherosclerosis progression. Precise targeting of specific immune system components involved in atherosclerosis, rather than broad suppression of the immune system with anti-inflammatory agents, can more accurately regulate the progress of atherosclerosis with fewer side effects. In this review, we cover the most recent advances in the field of atherosclerosis to understand the role of various immune cells on its development. We focus on the complex network of immune cells and the interaction between the innate immune system and adaptive immune system.

Multiparameter MRI-based radiomics nomogram for preoperative prediction of brain invasion in atypical meningioma:a multicentre study.

OBJECTIVE: To develop a nomogram based on tumor and peritumoral edema (PE) radiomics features extracted from preoperative multiparameter MRI for predicting brain invasion (BI) in atypical meningioma (AM). METHODS: In this retrospective study, according to the 2021 WHO classification criteria, a total of 469 patients with pathologically confirmed AM from three medical centres were enrolled and divided into training (n = 273), internal validation (n = 117) and external validation (n = 79) cohorts. BI was diagnosed based on the histopathological examination. Preoperative contrast-enhanced T1-weighted MR images (T1C) and T2-weighted MR images (T2) for extracting meningioma features and T2-fluid attenuated inversion recovery (FLAIR) sequences for extracting meningioma and PE features were obtained. The multiple logistic regression was applied to develop separate multiparameter radiomics models for comparison. A nomogram was developed by combining radiomics features and clinical risk factors, and the clinical usefulness of the nomogram was verified using decision curve analysis. RESULTS: Among the clinical factors, PE volume and PE/tumor volume ratio are the risk of BI in AM. The combined nomogram based on multiparameter MRI radiomics features of meningioma and PE and clinical indicators achieved the best performance in predicting BI in AM, with area under the curve values of 0.862 (95% CI, 0.819-0.905) in the training cohort, 0.834 (95% CI, 0.780-0.908) in the internal validation cohort and 0.867 (95% CI, 0.785-0.950) in the external validation cohort, respectively. CONCLUSIONS: The nomogram based on tumor and PE radiomics features extracted from preoperative multiparameter MRI and clinical factors can predict the risk of BI in patients with AM.

bHLH transcription factor EcdR controls conidia production, pigmentation and virulence in Aspergillus fumigatus.

Invasive Aspergillus fumigatus infection is a disease with high morbidity and mortality rates. Abnormalities in sporulation and pigmentation can significantly alter the pathogenicity of A. fumigatus, thus the mechanisms of conidiation and pigment biosynthesis have gained increasing attention. In Aspergillus oryzae, a novel predicted bHLH protein-encoding gene, ecdR, plays a role in asexual development, and its ortholog has also been characterized in A. nidulans. Herein, we determined its role in A. fumigatus by testing whether ecdR deletion affects asexual development, melanin synthesis, and regulation of virulence in this fungus. Our study shows that EcdR controls conidia and melanin production in A. fumigatus. In addition, we found that virulence in the ΔecdR strain was significantly reduced in the infection model of immunodeficiency mice.

Integrative bulk and single-cell transcriptome profiling analysis reveals IFI27 as a novel interferon-stimulated gene in dengue.

The dengue virus (DENV) is a public health threat to humans. Increased vascular permeability, coagulopathy, and hemorrhagic diathesis are the pathophysiological hallmarks of severe dengue. However, although the interferon (IFN)-mediated innate immune response forms the backbone of cell-autonomous defense against pathogens, the exact IFN-stimulated genes (ISGs) involved in DENV infection remain to be determined. The present study collected transcriptomic data sets of peripheral blood mononuclear cells from DENV patients and healthy volunteers from public data repositories. Also, lentivirus and plasmid were used to overexpress and knockdown IFI27. Initially, differentially expressed genes were filtered, and gene set enrichment analysis (GSEA) was performed to assess related pathways. Subsequently, the least absolute shrinkage and selection operator regression and support vector machine-recursive feature elimination algorithms were used to screen crucial genes. The receiver operating characteristic curve analysis was then employed to test diagnostic efficacy. Next, CIBERSORT was used to analyze immune infiltration in 22 immune cell subsets. Additionally, to dissect high-resolution molecular phenotypes directly from individual cells and the cellular interactions between immune cell subpopulations, single-cell RNA sequencing (scRNA-seq) was performed. We found that the IFN-stimulated gene IFN-α-inducible protein 27 (IFI27) was highly expressed in dengue patients by leveraging bioinformatics analysis and machine learning algorithms. This finding was further validated in two independent published databases. In addition, IFI27 overexpression positively regulated DENV-2 infection, whereas IFI27 knockdown has the opposite effect. Consistently, scRNA-seq analysis supported this conclusion, along with further dissection of increased IFI27 expression mainly concentrated in monocytes and plasmacytoid dendritic cells. We also demonstrated that IFI27 inhibited dengue infection. Moreover, IFI27 was positively correlated with monocytes, M1 macrophages, activated dendritic cells, plasma cells, and resting mast cells and negatively correlated with CD8 T cells, γδ T cells, and naïve B cells. GSEA revealed that IFI27 was primarily enriched in the innate immune response, regulation of the viral life cycle, and JAK-STAT signaling pathway. Notably, the interactions between LGALS9 and its receptor CD47 were markedly increased in dengue patients compared to healthy controls, based on cell-cell communication analysis. Our findings reveal, for the first time, that IFI27 is a key ISG in DENV infection. Given that the innate immune system plays a significant role in antagonizing DENV invasion, while ISGs are the ultimate antiviral effectors, IFI27 may serve as a potential diagnostic marker and therapeutic target in dengue, although further validation is warranted.

Stem cells therapy for diabetes: from past to future.

Diabetes mellitus is a chronic disease of carbohydrate metabolism characterized by uncontrolled hyperglycemia due to the body's impaired ability to produce or respond to insulin. Oral or injectable exogenous insulin and its analogs cannot mimic endogenous insulin secreted by healthy individuals, and pancreatic and islet transplants face a severe shortage of sources and transplant complications, all of which limit the widespread use of traditional strategies in diabetes treatment. We are now in the era of stem cells and their potential in ameliorating human disease. At the same time, the rapid development of gene editing and cell-encapsulation technologies has added to the wings of stem cell therapy. However, there are still many unanswered questions before stem cell therapy can be applied clinically to patients with diabetes. In this review, we discuss the progress of strategies to obtain insulin-producing cells from different types of stem cells, the application of gene editing in stem cell therapy for diabetes, as well as summarize the current advanced cell encapsulation technologies in diabetes therapy and look forward to the future development of stem cell therapy in diabetes.

Research trends on the relationship between Helicobacter pylori and microbiota: A bibliometric analysis.

BACKGROUND: Increasing evidence has indicated that Helicobacter pylori infection is associated with the complex microbiota in the digestive tract of the human body. We aimed to assess the research trends and hotspots in the field of H. pylori and microbiota using a quantitative method. MATERIALS AND METHODS: The clinical studies on H. pylori and microbiota published from 2001 to 2022 were extracted from the Web of Science database. We visualized and analyzed countries/regions, institutions, authors, journals, and keywords through VOSviewer and CiteSpace software. The test techniques, specimen type, as well as microbiota variation after H. pylori infection and eradication were also evaluated. RESULTS: A total of 98 publications were finally identified, and the number of annual papers increased gradually. China showed its dominant position in the publication outputs, and Nanchang University was the most productive institution. Cong He, Xu Shu, and Yin Zhu published the highest number of papers, whereas Helicobacter was the most productive journal. "Helicobacter pylori" ranked highest in the keyword occurrences. 16S rRNA gene sequencing was the most frequently used method for microbiota analysis. Fecal samples had the highest frequency of use, followed by gastric mucosa and saliva. H. pylori infection was associated with the alterations of microbiota through the digestive tract, characterized by the enrichment of Helicobacter in the stomach. Triple and quadruple therapy were the most utilized eradication regimens, and probiotics supplementation therapy has been proven to reduce side effects and restore microbial diversity. CONCLUSIONS: This bibliometric analysis provides an overview of advancements in the field of H. pylori and microbiota. While numerous studies have been conducted on the correlation between H. pylori and the alterations of microbiota, future research is warranted to investigate the mechanisms underlying the interplay between H. pylori and other microbes in the development of related diseases.

Charge-to-spin conversion in fully epitaxial Ru/Cu hybrid nanolayers with interface control.

The demonstration of the charge-to-spin conversion, especially with enhanced spin Hall conductivity, is crucial for the development of energy-efficient spintronic devices such as spin-orbit torque (SOT) based magnetoresistive random access memories. In this work, fully epitaxial Ru/Cu heterostructures were fabricated with interface engineering and nanolayer insertions consisting of Cu (1 nm)/Ru (1 nm) structures with different numbers of periods. The atomically controlled interface was confirmed by the high-resolution high-angle annular dark-field scanning transmission electron microscopy, and the epitaxial relationship persists even in the hybrid nanolayer insertion structures. The spin current generation was detected by the measurement of unidirectional spin Hall magnetoresistance, and the effective damping-like spin Hall efficiency (ξDL) was further quantitatively evaluated by the spin-torque ferromagnetic resonance with thickness dependence of the ferromagnetic layer. It is found that the sharp interface Ru/Cu film has a sizeableξDLof -2.2% and the insertion of Cu/Ru nanolayers at the interface can increase theξDLvalue to -3.7%. The former could be attributed to the interface spin-orbit filtering effect and the latter may be further understood by the intrinsic contribution from the local electronic structure tuning due to the lattice distortion near the interface. A large effective spin Hall conductivity is achieved to be (3∼5) × 105ℏ2eΩ-1m-1in the epitaxial Ru/Cu hybrid nanolayers, which is in the same range as that of platinum. This work indicates that the interfacial control with hybrid nanolayer structures can extend the SOT-based materials to highly conductive metals, even with weak spin-orbit interactions, toward high stability, low cost, and low energy consumption for spintronic applications.

Clinical characteristics and risk factors of organ failure and death in necrotizing pancreatitis.

BACKGROUND: Organ failure (OF) and death are considered the most significant adverse outcomes in necrotizing pancreatitis (NP). However, there are few NP-related studies describing the clinical traits of OF and aggravated outcomes. PURPOSE: An improved insight into the details of OF and death will be helpful to the management of NP. Thus, in our research, we addressed the risk factors of OF and death in NP patients. METHODS: We performed a study of 432 NP patients from May 2017 to December 2021. All patients with NP were followed up for 36 months. The primary end-points were risk factors of OF and death in NP patients. The risk factors were evaluated by logistic regression analysis. RESULTS: NP patients with OF or death patients were generally older, had a higher APACHE II score, longer hospital stay, longer ICU stay, as well as a higher incidence of severe acute pancreatitis (SAP), shock and pancreatic necrosis. Independent risk factors related to OF included BMI, APACHE II score and SAP (P < 0.05). Age, shock and APACHE II score (P < 0.05) were the most significant factors correlated with the risk of death in NP patients. Notably, increased mortality was linked to the number of failed organs. CONCLUSIONS: NP is a potentially fatal disease with a long hospital or ICU stay. Our study indicated that the incidence of OF and death in NP patients was 69.9% and 10.2%, respectively. BMI, SAP, APACHE II score, age and shock are potential risk factors of OF and death in NP patients. Clinicians should focus on these factors for early diagnosis and appropriate therapy.

Purinergic Receptor P2Y6 Is a Negative Regulator of NK Cell Maturation and Function.

NK cells are critical innate immune cells that target the tumor cells and cancer-initiating cells and clear viruses by producing cytokines and cytotoxic granules. However, the role of the purinergic receptor P2Y6 in the NK cells remains largely unknown. In this study, we discovered that the expression of P2Y6 was decreased upon the activation of the NK cells. Moreover, in the P2Y6-deficient mice, we found that the deficiency of P2Y6 promoted the development of the NK precursor cells into immature NK and mature NK cells. We also found that the P2Y6 deficiency increased, but the P2Y6 receptor agonist UDP or UDP analog 5-OMe-UDP decreased the production of IFN-γ in the activated NK cells. Furthermore, we demonstrated that the P2Y6-deficient NK cells exhibited stronger cytotoxicity in vitro and antimetastatic effects in vivo. Mechanistically, P2Y6 deletion promoted the expression of T-bet (encoded by Tbx21), with or without the stimulation of IL-15. In the absence of P2Y6, the levels of phospho-serine/threonine kinase and pS6 in the NK cells were significantly increased upon the stimulation of IL-15. Collectively, we demonstrated that the P2Y6 receptor acted as a negative regulator of the NK cell function and inhibited the maturation and antitumor activities of the NK cells. Therefore, inhibition of the P2Y6 receptor increases the antitumor activities of the NK cells, which may aid in the design of innovative strategies to improve NK cell-based cancer therapy.

Mechanism of highly efficient electrochemical degradation of antibiotic sulfadiazine using a layer-by-layer GNPs/PbO2 electrode.

A PbO2 electrode integrating electrocatalytic and adsorptive functions was successfully fabricated by embedding layer-by-layer graphene nanoplatelets (GNPs) into ß-PbO2 active layer (GNPs/PbO2) and employed as anode for high-efficient removal of sulfadiazine (SDZ). In electrochemical degradation experiments, SDZ was quickly enriched on the surface of GNPs/PbO2 film via adsorption and then oxidized by ⋅OH in-site. In terms of the electrocatalytic performance and adsorption of electrode, the optimal electrodeposition time for each ß-PbO2 outer layer was 4 min (GNPs/PbO2-4). Compared with conventional PbO2 electrode, the layer-by-layer GNPs resulted in the smaller crystal size and denser surface of PbO2 electrode, thus facilitating the generation of active oxygen species. At the same time, the specific surface area, oxygen evolution potential (OEP) of the anode were enhanced and the charge-transfer resistance was reduced. For GNPs/PbO2-4 anode, the optimal conditions of electrochemical oxidation of SDZ were identified as initial pH 9, 50 mg/L of SDZ and 20 mA/cm2 of current density using response surface methodology (RSM), 98.15% of SDZ could be removed in this case. The contribution of radical oxidation and non-radical oxidation to SDZ removal was about 79% and 21%, respectively. Moreover, the reaction pathways of SDZ on the GNPs/PbO2-4 electrode involving hydroxylation, radical reaction and ring cleavage were speculated. Finally, the continuous SDZ degradation and accelerated service lifetime test suggested that the GNPs/PbO2-4 electrode was shown to be stable and repeatable, and the Pb2+ concentration was measured to ensure the safety of the treated solution. Consequently, the above findings provide an innovative way to design and prepare an effective and stable PbO2 electrode for electrochemical degradation of antibiotic wastewater.

Engineered extracellular vesicles mediated CRISPR-induced deficiency of IQGAP1/FOXM1 reverses sorafenib resistance in HCC by suppressing cancer stem cells.

BACKGROUND: Sorafenib resistance poses therapeutic challenges in HCC treatment, in which cancer stem cells (CSCs) plays a crucial role. CRISPR/Cas9 can be utilized as a potential technique to overcome the drug resistance. However, a safe, efficient and target specific delivery of this platform remains challenging. Extracellular vesicles (EVs), the active components of cell to cell communication, hold promising benefits as delivery platform. RESULTS: Herein we report the normal epithelial cell -derived EVs engineered with HN3(HLC9-EVs) show competing tumor targeting ability. Anchoring HN3 to the membrane of the EVs through LAMP2, drastically increased the specific homing of HLC9-EVs to GPC3+Huh-7 cancer cells rather than co-cultured GPC3-LO2 cells. Combination therapy of HCC with sorafenib and HLC9-EVs containing sgIF to silence IQGAP1 (protein responsible for reactivation of Akt/PI3K signaling in sorafenib resistance) and FOXM1 (self-renewal transcription factor in CSCs attributed to sorafenib resistance), exhibited effective synergistic anti-cancer effect both in vitro and in vivo. Our results also showed that disruption of IQGAP1/FOXM1 resulted in the reduction of CD133+ population that contribute to the stemness of liver cancer cells. CONCLUSION: By reversing sorafenib resistance using combination therapeutic approach with engineered EVs encapsulated CRISPR/Cas9 and sorafenib, our study foreshadows a path for a better, accurate, reliable and successful anti-cancer therapy in the future.

Interpretable machine-learning model for Predicting the Convalescent COVID-19 patients with pulmonary diffusing capacity impairment.

INTRODUCTION: The COVID-19 patients in the convalescent stage noticeably have pulmonary diffusing capacity impairment (PDCI). The pulmonary diffusing capacity is a frequently-used indicator of the COVID-19 survivors' prognosis of pulmonary function, but the current studies focusing on prediction of the pulmonary diffusing capacity of these people are limited. The aim of this study was to develop and validate a machine learning (ML) model for predicting PDCI in the COVID-19 patients using routinely available clinical data, thus assisting the clinical diagnosis. METHODS: Collected from a follow-up study from August to September 2021 of 221 hospitalized survivors of COVID-19 18 months after discharge from Wuhan, including the demographic characteristics and clinical examination, the data in this study were randomly separated into a training (80%) data set and a validation (20%) data set. Six popular machine learning models were developed to predict the pulmonary diffusing capacity of patients infected with COVID-19 in the recovery stage. The performance indicators of the model included area under the curve (AUC), Accuracy, Recall, Precision, Positive Predictive Value(PPV), Negative Predictive Value (NPV) and F1. The model with the optimum performance was defined as the optimal model, which was further employed in the interpretability analysis. The MAHAKIL method was utilized to balance the data and optimize the balance of sample distribution, while the RFECV method for feature selection was utilized to select combined features more favorable to machine learning. RESULTS: A total of 221 COVID-19 survivors were recruited in this study after discharge from hospitals in Wuhan. Of these participants, 117 (52.94%) were female, with a median age of 58.2 years (standard deviation (SD) = 12). After feature selection, 31 of the 37 clinical factors were finally selected for use in constructing the model. Among the six tested ML models, the best performance was accomplished in the XGBoost model, with an AUC of 0.755 and an accuracy of 78.01% after experimental verification. The SHAPELY Additive explanations (SHAP) summary analysis exhibited that hemoglobin (Hb), maximal voluntary ventilation (MVV), severity of illness, platelet (PLT), Uric Acid (UA) and blood urea nitrogen (BUN) were the top six most important factors affecting the XGBoost model decision-making. CONCLUSION: The XGBoost model reported here showed a good prognostic prediction ability for PDCI of COVID-19 survivors during the recovery period. Among the interpretation methods based on the importance of SHAP values, Hb and MVV contributed the most to the prediction of PDCI outcomes of COVID-19 survivors in the recovery period.

Unleashing the Potential of EIL Transcription Factors in Enhancing Sweet Orange Resistance to Bacterial Pathologies: Genome-Wide Identification and Expression Profiling.

The ETHYLENE INSENSITIVE3-LIKE (EIL) family is one of the most important transcription factor (TF) families in plants and is involved in diverse plant physiological and biochemical processes. In this study, ten EIL transcription factors (CsEILs) in sweet orange were systematically characterized via whole-genome analysis. The CsEIL genes were unevenly distributed across the four sweet orange chromosomes. Putative cis-acting regulatory elements (CREs) associated with CsEIL were found to be involved in plant development, as well as responses to biotic and abiotic stress. Notably, quantitative reverse transcription polymerase chain reaction (qRT-PCR) revealed that CsEIL genes were widely expressed in different organs of sweet orange and responded to both high and low temperature, NaCl treatment, and to ethylene-dependent induction of transcription, while eight additionally responded to Xanthomonas citri pv. Citri (Xcc) infection, which causes citrus canker. Among these, CsEIL2, CsEIL5 and CsEIL10 showed pronounced upregulation. Moreover, nine genes exhibited differential expression in response to Candidatus Liberibacter asiaticus (CLas) infection, which causes Citrus Huanglongbing (HLB). The genome-wide characterization and expression profile analysis of CsEIL genes provide insights into the potential functions of the CsEIL family in disease resistance.

Da-Cheng-Qi decoction improves severe acute pancreatitis-associated acute lung injury by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response in rats.

CONTEXT: Da-Cheng-Qi Decoction (DCQD) has a significant effect on Severe Acute Pancreatitis-Associated Acute Lung Injury (SAP-ALI). OBJECTIVE: To explore the mechanism of DCQD in the treatment of SAP-ALI based on intestinal barrier function and intestinal lymphatic pathway. MATERIALS AND METHODS: Forty-five Sprague-Dawley rats were divided into three groups: sham operation, model, and DCQD. The SAP model was induced by a retrograde infusion of 5.0% sodium taurocholate solution (1 mg/kg) at a constant rate of 12 mL/h using an infusion pump into the bile-pancreatic duct. Sham operation and model group were given 0.9% normal saline, while DCQD group was given DCQD (5.99 g/kg/d) by gavage 1 h before operation and 1, 11 and 23 h after operation. The levels of HMGB1, RAGE, TNF-α, IL-6, ICAM-1, d-LA, DAO in blood and MPO in lung were detected using ELISA. The expression of HMGB1, RAGE, NF-κB p65 in mesenteric lymph nodes and lung were determined. RESULTS: Compared with SAP group, DCQD significantly reduced the histopathological scoring of pancreatic tissue (SAP, 2.80 ± 0.42; DCQD, 2.58 ± 0.52), intestine (SAP, 3.30 ± 0.68; DCQD, 2.50 ± 0.80) and lung (SAP, 3.30 ± 0.68; DCQD, 2.42 ± 0.52). DCQD reduced serum HMGB1 level (SAP, 134.09 ± 19.79; DCQD, 88.05 ± 9.19), RAGE level (SAP, 5.05 ± 1.44; DCQD, 2.13 ± 0.54). WB and RT-PCR showed HMGB1-RAGE pathway was inhibited by DCQD (p < 0.01). DISCUSSION AND CONCLUSIONS: DCQD improves SAP-ALI in rats by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response.

Responses of soil pH to no-till and the factors affecting it: A global meta-analysis.

No-till (NT) is a sustainable option because of its benefits in controlling erosion, saving labor, and mitigating climate change. However, a comprehensive assessment of soil pH response to NT is still lacking. Thus, a global meta-analysis was conducted to determine the effects of NT on soil pH and to identify the influential factors and possible consequences based on the analysis of 114 publications. When comparing tillage practices, the results indicated an overall significant decrease by 1.33 ± 0.28% in soil pH under NT than that under conventional tillage (p < .05). Soil texture, NT duration, mean annual temperature (MAT), and initial soil pH are the critical factors affecting soil pH under NT. Specifically, with significant variations among subgroups, when compared to conventional tillage, the soil under NT had lower relative changes in soil pH observed on clay loam soil (-2.44%), long-term implementation (-2.11% for more than 15 years), medium MAT (-1.87% in the range of 8-16℃), neutral soil pH (-2.28% for 6.5 < initial soil pH < 7.5), mean annual precipitation (-1.95% in the range of 600-1200 mm), in topsoil layers (-2.03% for 0-20 cm), with crop rotation (-1.98%), N fertilizer input (the same for NT and conventional tillage) of 100-200 kg N ha-1 (-1.83%), or crop residue retention (-1.52%). Changes in organic matter decomposition under undisturbed soil and with crop residue retention might lead to a higher concentration of H+ and lower of basic cations (i.e., calcium, magnesium, and potassium), which decrease the soil pH, and consequently, impact nutrient dynamics (i.e., soil phosphorus) in the surface layer under NT. Furthermore, soil acidification may be aggravated by NT within site-specific conditions and improper fertilizer and crop residue management and consequently leading to adverse effects on soil nutrient availability. Thus, there is a need to identify strategies to ameliorate soil acidification under NT to minimize the adverse consequences.

Probiotics mitigate Helicobacter pylori-induced gastric inflammation and premalignant lesions in INS-GAS mice with the modulation of gastrointestinal microbiota.

BACKGROUND: Dysbiosis of gastric microbiota including Helicobacter pylori (H. pylori) infection is associated with the development of stomach cancer. Probiotics have been shown to attenuate H. pylori-induced gastritis, although their role in cancer prevention remains unclear. Thus, we aimed to explore the effects of probiotics on H. pylori-induced carcinogenesis and the alterations of gastrointestinal microbiota. METHODS: Male INS-GAS mice were randomly allocated to H. pylori-infected and non-infected groups. After 4 weeks, probiotic combination (containing Lactobacillus salivarius and Lactobacillus rhamnosus) was administered in drinking water for 12 weeks. Stomachs were collected for RNA-Sequencing and the differentially expressed genes were validated using RT profiler PCR array. 16S rRNA gene sequencing was performed to assess the alterations of gastrointestinal microbiota. RESULTS: Probiotics significantly alleviate H. pylori-induced gastric pathology, including reduced infiltration of inflammation and lower incidence of precancerous lesions. RNA-Sequencing results showed that probiotics treatment decreased expressions of genes involved in pro-inflammatory pathways, such as NF-κB, IL-17, and TNF signaling pathway. Of note, probiotics did not suppress the growth of H. pylori, but dramatically reshaped the structure of both gastric and gut microbiota. The microbial diversity was increased in H. pylori-infected group after probiotics treatment. While gastric cancer-associated genera Lactobacillus and Staphylococcus were enriched in the stomach of H. pylori-infected group, the beneficial short-chain fatty acids-producing bacteria, including Bacteroides, Alloprevotella, and Oscellibacter, were more abundant in mice treated with probiotics. Additionally, probiotics restored the H. pylori-induced reduction of anti-inflammatory bacterium Faecalibaculum in the gut. CONCLUSIONS: Probiotics therapy can protect against H. pylori-associated carcinogenesis probably through remodeling gastrointestinal microbiota, which in turn prevent host cells from malignant transformation.

Optimization of vonoprazan-amoxicillin dual therapy for eradicating Helicobacter pyloriinfection in China: A prospective, randomized clinical pilot study.

BACKGROUND: Vonoprazan-amoxicillin (VA) dual therapy has been shown to achieve acceptable cure rates for treatment of Helicobacter pylori(H. pylori) in Japan. Its effectiveness in other regions is unknown. We aimed to explore the efficacy of VA dual therapy as first-line treatment for H. pyloriinfection in China. METHODS: This was a single center, prospective, randomized clinical pilot study conducted in China. Treatment naive H. pyloriinfected patients were randomized to receive either low- or high-dose amoxicillin-vonoprazan consisting of amoxicillin 1 g either b.i.d. or t.i.d plus VPZ 20 mg b.i.d for 7 or 10 days. 13 C-urea breath tests were used to access the cure rate at least 4 weeks after treatment. RESULTS: Three hundred and twenty-three patients were assessed, and 119 subjects were randomized. The eradication rates of b.i.d. amoxicillin for 7 and 10 days, t.i.d. amoxicillin for 7 and 10 days were 66.7% (16/24), 89.2% (33/37), 81.0% (17/21), and 81.1% (30/37) (p = .191) by intention-to-treat analysis, respectively, and 72.7% (16/22), 89.2% (33/37), 81.0% (17/21), and 81.1% (30/37) (p = .454) by per-protocol analysis, respectively. CONCLUSION: Neither 7- or 10-day VA dual therapy with b.i.d. or t.i.d. amoxicillin provides satisfied efficacy as the first-line treatment for H. pyloriinfection in China. Further optimization is needed.

Analysis of oral microbiota alterations induced by Helicobacter pylori infection and vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication.

BACKGROUND: The oral cavity is considered a potential reservoir of Helicobacter pylori (H. pylori), and the imbalance of oral microbiota directly reflects the health of the host. We aimed to explore the relationship among oral microbiota, H. pylori infection, and vonoprazan-amoxicillin (VA) dual therapy for H. pylori eradication. METHODS: Helicobacter pylori-positive patients were randomized into low- or high-dose VA dual therapy (i.e., amoxicillin 1 g b.i.d. or t.i.d. and vonoprazan 20 mg b.i.d) for 7 or 10 days. H. pylori-negative patients served as normal controls. Saliva samples were collected from 41 H. pylori-positive patients and 13 H. pylori-negative patients. The oral microbiota was analyzed by 16S rRNA gene sequencing, followed by bioinformatics analysis. RESULTS: Helicobacter pylori-positive patients had higher richness and diversity and better evenness of oral microbiota than normal controls. Beta diversity analysis estimated by Bray-Curtis or weighted UniFrac showed distinct clustering between H. pylori-positive patients and normal controls. The number of bacterial interactions was reduced in H. pylori-positive patients compared with that in negative patients. Forty-one patients evaluated before and after successful H. pylori eradication were divided into low (L-VA) and high dose (H-VA) amoxicillin dose groups. The alpha and beta diversity of the oral microbiota between L-VA and H-VA patients exhibited no differences at the three time points (before eradication, after eradication, and at confirmation of H. pylori infection cure). CONCLUSION: Helicobacter pylori infection could alter the diversity, composition, and bacterial interactions of the oral microbiota. Both L-VA and H-VA dual therapy showed minimal influence on the oral microbiota.

Shikonin N-benzyl matrinic acid ester derivatives as novel telomerase inhibitors with potent activity against lung cancer cell lines.

In this study, a series of novel shikonin N-benzyl matrinic acid ester derivatives (PMMB-299-PMMB-310) were synthesized and tested for their ability to inhibit the proliferation of cancer cells. Compared with shikonin and matrine, some of the ester derivatives were found to exhibit better anti-proliferative activity against seven different cancer cell lines, with less cytotoxicity toward non-cancerous cells. The strongest anti-proliferative activity was exhibited by PMMB-302, which had an IC50 value of 2.71 µM against A549 cells. The compound caused cell cycle arrest in the G2/M phase and induced apoptosis. Effects on the expression of apoptosis-related molecules such as Bcl2, Bcl-XL, caspase-3, caspase-9 and FADD suggested that PMMB-302 has tumor suppressive roles in lung cancer cells. In addition, PMMB-302 inhibited expression of telomerase core proteins, dyskerin and NHP2, and telomerase reverse transcriptase RNA. Moreover, molecular docking of PMMB-302 was subsequently conducted to determine the probable binding mode with telomerase. Taken together, the results indicate that PMMB-302 acts as a tumor suppressor in lung cancer cells by negatively regulating telomerase expression.