Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions.

BACKGROUND: Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. METHODS: A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). RESULTS: IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1ß). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. CONCLUSION: Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.

Hepatic mitochondrial NAD + transporter SLC25A47 activates AMPKα mediating lipid metabolism and tumorigenesis.

BACKGROUND AIMS: SLC25A47 was initially identified as a mitochondrial HCC-downregulated carrier protein, but its physiological functions and transport substrates are unknown. We aimed to investigate the physiological role of SLC25A47 in hepatic metabolism. APPROACH RESULTS: In the treatment of hepatocytes with metformin, we found that metformin can transcriptionally activate the expression of Slc25a47 , which is required for AMP-activated protein kinase α (AMPKα) phosphorylation. Slc25a47 -deficient mice had increased hepatic lipid content, triglycerides, and cholesterol levels, and we found that Slc25a47 deficiency suppressed AMPKα phosphorylation and led to an increased accumulation of nuclear SREBPs, with elevated fatty acid and cholesterol biosynthetic activities. Conversely, when Slc25a47 was overexpressed in mouse liver, AMPKα was activated and resulted in the inhibition of lipogenesis. Moreover, using a diethylnitrosamine-induced mouse HCC model, we found that the deletion of Slc25a47 promoted HCC tumorigenesis and development through the activated mammalian target of rapamycin cascade. Employing homology modeling of SLC25A47 and virtual screening of the human metabolome database, we demonstrated that NAD + was an endogenous substrate for SLC25A47, and the activity of NAD + -dependent sirtuin 3 declined in Slc25a47 -deficient mice, followed by inactivation of AMPKα. CONCLUSIONS: Our findings reveal that SLC25A47, a hepatocyte-specific mitochondrial NAD + transporter, is one of the pharmacological targets of metformin and regulates lipid homeostasis through AMPKα, and may serve as a potential drug target for treating NAFLD and HCC.

Stop codon variant in EFEMP1 is associated with primary open-angle glaucoma due to impaired regulation of aqueous humor outflow.

It is known that the actin cytoskeleton and its associated cellular interactions in the trabecular meshwork (TM) and juxtacanalicular tissues mainly contribute to the formation of resistance to aqueous outflow of the eye. Fibulin-3, encoded by EFEMP1 gene, has a role in extracellular matrix (ECM) modulation, and interacts with enzymatic ECM regulators, but the effects of fibulin-3 on TM cells has not been explored. Here, we report a stop codon variant (c.T1480C, p.X494Q) of EFEMP1 that co-segregates with primary open angle glaucoma (POAG) in a Chinese pedigree. In the human TM cells, overexpression of wild-type fibulin-3 reduced intracellular actin stress fibers formation and the extracellular fibronectin levels by inhibiting Rho/ROCK signaling. TGFß1 up-regulated fibulin-3 protein levels in human TM cells by activating Rho/ROCK signaling. In rat eyes, overexpression of wild-type fibulin-3 decreased the intraocular pressure and the fibronectin expression of TM, however, overexpression of mutant fibulin-3 (c.T1480C, p.X494Q) showed opposite effects in cells and rat eyes. Taken together, the EFEMP1 variant may impair the regulatory capacity of fibulin-3 which has a role for modulating the cell contractile activity and ECM synthesis in TM cells, and in turn may maintain normal resistance of aqueous humor outflow. This study contributes to the understanding of the important role of fibulin-3 in TM pathophysiology and provides a new possible POAG therapeutic approach.

KDM6B promotes PARthanatos via suppression of O6-methylguanine DNA methyltransferase repair and sustained checkpoint response.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA damage sensor and contributes to both DNA repair and cell death processes. However, how PARP-1 signaling is regulated to switch its function from DNA repair to cell death remains largely unknown. Here, we found that PARP-1 plays a central role in alkylating agent-induced PARthanatic cancer cell death. Lysine demethylase 6B (KDM6B) was identified as a key regulator of PARthanatos. Loss of KDM6B protein or its demethylase activity conferred cancer cell resistance to PARthanatic cell death in response to alkylating agents. Mechanistically, KDM6B knockout suppressed methylation at the promoter of O6-methylguanine-DNA methyltransferase (MGMT) to enhance MGMT expression and its direct DNA repair function, thereby inhibiting DNA damage-evoked PARP-1 hyperactivation and subsequent cell death. Moreover, KDM6B knockout triggered sustained Chk1 phosphorylation and activated a second XRCC1-dependent repair machinery to fix DNA damage evading from MGMT repair. Inhibition of MGMT or checkpoint response re-sensitized KDM6B deficient cells to PARthanatos induced by alkylating agents. These findings provide new molecular insights into epigenetic regulation of PARP-1 signaling mediating DNA repair or cell death and identify KDM6B as a biomarker for prediction of cancer cell vulnerability to alkylating agent treatment.

Irisin combined index to diagnose central precocious puberty in girls: a cross-sectional study.

BACKGROUND: To investigate serum irisin levels in girls at different developmental status and explore the significance of irisin for the diagnosis of central precocious puberty (CPP) in girls. METHODS: In this cross-sectional study 111 girls were enrolled, including 43 cases of CPP, 44 cases of peripheral precocious puberty (PPP) and 24 cases of girls with normal sexual development as controls. The data on age, weight and height, measured blood levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and irisin were collected. Pelvic Doppler ultrasound was performed to evaluate uterine length, transverse diameter, anteroposterior diameter. The girls were divided into non-CPP group and CPP group according to gonadotropin-releasing hormone (GnRH) stimulation test. RESULTS: Serum irisin levels were significantly higher in CPP group than in PPP group and normal control group. Serum irisin level was positively correlated with basal LH level, basal FSH level, peak LH level, peak LH /FSH ratio, uterine volume, bone age, and bone age index. The area under the curve, cut-off value, sensitivity and specificity of serum irisin were 0.958, 219.255 pg/ml, 100% and 80.6%. The combined diagnosis of CPP in girls by serum irisin and serum basal LH combined with uterine volume had an AUC, sensitivity, and specificity of 0.994, 97.6%, and 100%, superior to that of the single index. CONCLUSIONS: Serum irisin level in girls with CPP is significantly increased. An irisin combined index could help the diagnosis of CPP in girls.

Stroke in patients with heart failure and reduced or preserved ejection fraction.

AIMS: Stroke is an important problem in patients with heart failure (HF), but the intersection between the two conditions is poorly studied across the range of ejection fraction. The prevalence of history of stroke and related outcomes were investigated in patients with HF. METHODS AND RESULTS: Individual patient meta-analysis of seven clinical trials enrolling patients with HF with reduced (HFrEF) and preserved ejection fraction (HFpEF). Of the 20 159 patients with HFrEF, 1683 (8.3%) had a history of stroke, and of the 13 252 patients with HFpEF, 1287 (9.7%) had a history of stroke. Regardless of ejection fraction, patients with a history of stroke had more vascular comorbidity and worse HF. Among those with HFrEF, the incidence of the composite of cardiovascular death, HF hospitalization, stroke, or myocardial infarction was 18.23 (16.81-19.77) per 100 person-years in those with prior stroke vs. 13.12 (12.77-13.48) in those without [hazard ratio 1.37 (1.26-1.49), P < 0.001]. The corresponding rates in patients with HFpEF were 14.16 (12.96-15.48) and 9.37 (9.06-9.70) [hazard ratio 1.49 (1.36-1.64), P < 0.001]. Each component of the composite was more frequent in patients with stroke history, and the risk of future stroke was doubled in patients with prior stroke. Among patients with prior stroke, 30% with concomitant atrial fibrillation were not anticoagulated, and 29% with arterial disease were not taking statins; 17% with HFrEF and 38% with HFpEF had uncontrolled systolic blood pressure (≥140 mmHg). CONCLUSION: Heart failure patients with a history of stroke are at high risk of subsequent cardiovascular events, and targeting underutilization of guideline-recommended treatments might be a way to improve outcomes in this high-risk population.

Heart failure, peripheral artery disease, and dapagliflozin: a patient-level meta-analysis of DAPA-HF and DELIVER.

AIMS: Because an increased risk of amputation with canagliflozin was reported in the CANVAS trials, there has been a concern about the safety of sodium-glucose cotransporter 2 inhibitors in patients with peripheral artery disease (PAD) who are at higher risk of amputation. METHODS AND RESULTS: A patient-level pooled analysis of the DAPA-HF and DELIVER trials, which evaluated the efficacy and safety of dapagliflozin in patients with heart failure (HF) with reduced, mildly reduced/preserved ejection fraction, respectively, was conducted. In both trials, the primary outcome was the composite of worsening HF or cardiovascular death, and amputation was a prespecified safety outcome. Peripheral artery disease history was available for 11 005 of the total 11 007 patients. Peripheral artery disease was reported in 809 of the 11 005 patients (7.4%). Median follow-up was 22 months (interquartile range 17-30). The rate of the primary outcome (per 100 person-years) was higher in PAD patients than that in non-PAD patients: 15.1 [95% confidence interval (CI) 13.1-17.3) vs. 10.6 (10.2-11.1]; adjusted hazard ratio 1.23 (95% CI 1.06-1.43). The benefit of dapagliflozin on the primary outcome was consistent in patients with [hazard ratio 0.71 (95% CI 0.54-0.94)] and without PAD [0.80 (95% CI 0.73-0.88)] (Pinteraction = 0.39). Amputations, while more frequent in PAD patients, were not more common with dapagliflozin, compared with placebo, irrespective of PAD status (PAD, placebo 4.2% vs. dapagliflozin 3.7%; no PAD, placebo 0.4% vs. dapagliflozin 0.4%) (Pinteraction = 1.00). Infection rather than ischaemia was the main trigger for amputation, even in patients with PAD. CONCLUSION: The risk of worsening HF or cardiovascular death was higher in patients with PAD, as was the risk of amputation. The benefits of dapagliflozin were consistent in patients with and without PAD, and dapagliflozin did not increase the risk of amputation.

Vaccines and the Eye: Current Understanding of the Molecular and Immunological Effects of Vaccination on the Eye.

Vaccination is a public health cornerstone that protects against numerous infectious diseases. Despite its benefits, immunization implications on ocular health warrant thorough investigation, particularly in the context of vaccine-induced ocular inflammation. This review aimed to elucidate the complex interplay between vaccination and the eye, focusing on the molecular and immunological pathways implicated in vaccine-associated ocular adverse effects. Through an in-depth analysis of recent advancements and the existing literature, we explored various mechanisms of vaccine-induced ocular inflammation, such as direct infection by live attenuated vaccines, immune complex formation, adjuvant-induced autoimmunity, molecular mimicry, hypersensitivity reactions, PEG-induced allergic reactions, Type 1 IFN activation, free extracellular RNA, and specific components. We further examined the specific ocular conditions associated with vaccination, such as uveitis, optic neuritis, and retinitis, and discussed the potential impact of novel vaccines, including those against SARS-CoV-2. This review sheds light on the intricate relationships between vaccination, the immune system, and ocular tissues, offering insights into informed discussions and future research directions aimed at optimizing vaccine safety and ophthalmological care. Our analysis underscores the importance of vigilance and further research to understand and mitigate the ocular side effects of vaccines, thereby ensuring the continued success of vaccination programs, while preserving ocular health.

Ripasudil as a Potential Therapeutic Agent in Treating Secondary Glaucoma in HTLV-1-Uveitis: An In Vitro Analysis.

Human T-cell leukemia virus type 1 (HTLV-1), a virus that affects 5-10 million people globally, causes several diseases, including adult T-cell leukemia-lymphoma and HTLV-1-associated uveitis (HU). HU is prevalent in Japan and often leads to secondary glaucoma, which is a serious complication. We investigated the efficacy of ripasudil, a Rho-associated coiled coil-forming protein kinase inhibitor, in alleviating changes in human trabecular meshwork cells (hTM cells) infected with HTLV-1. HTLV-1-infected hTM cells were modeled in vitro using MT-2 cells, followed by treatment with varying concentrations of ripasudil. We assessed changes in cell morphology, viability, and inflammatory cytokine levels, as well as NF-κB activation. The results showed that ripasudil treatment changed the cell morphology, reduced the distribution of F-actin and fibronectin, and decreased the levels of certain inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-12. However, ripasudil did not significantly affect NF-κB activation or overall cell viability. These findings suggest that ripasudil has the potential to treat secondary glaucoma in patients with HU by modulating cytoskeletal organization and alleviating inflammation in HTLV-1-infected hTM cells. This study lays the foundation for further clinical studies exploring the effectiveness of ripasudil for the treatment of secondary glaucoma associated with HU.

Relationship between the volume of cases and in-hospital mortality in patients with cardiogenic shock receiving short-term mechanical circulatory support.

BACKGROUND: We examined the relationship between annual case volume at each hospital and outcome in cardiogenic shock (CS) patients receiving mechanical circulatory support (MCS) devices. METHODS: This cross-sectional study used the Japanese nationwide database to identify patients receiving short-term MCS for CS between April 2012 and March 2020. Of 65,837 patients, 3 subcohorts were created; the intra-aortic balloon pump (IABP) alone (n = 48,643), the extracorporeal membrane oxygenation (ECMO) (n = 16,871), and the Impella cohorts (n = 696). RESULTS: The median annual case volume was 13.5 (7.4-22.1) in the IABP alone cohort, 6.4 (3.4-11.0) in the ECMO cohort, and 7.5 (4.0-10.7) in the Impella cohort. The highest quintile for the volume of cases in the IABP alone and ECMO had the lowest in-hospital mortality (IABP alone, 25.1% in quintile 1 vs 15.2% in quintile 5; ECMO, 73.7% in quintile 1 in 67.4% in quintile 5). Adjusted ORs for in-hospital mortality decreased as case volume increased (IABP alone, 0.63 [0.58-0.68] in quintile 5; ECMO, 0.73 [0.65-0.82] in quintile 5, with the lowest quintile as reference) but did not decrease significantly in the Impella (0.90 [0.58-1.39] in tertile 3, with the lowest tertile as reference). In the continuous models with the case volume as a continuous variable, adjusted ORs for in-hospital mortality decreased to 28 IABP cases/year and 12 ECMO cases/year. They did not decrease or became almost flat above that. CONCLUSIONS: Higher volumes of IABP and ECMO are associated with a lower mortality. There is an upper limit to the decline. Centralizing patients with refractory CS in a particular hospital might improve patient outcomes in each region.

Helicity-resolved Raman scattering of MoS2 bulk crystal.

Helicity-resolved Raman spectroscopy (HRRS) can effectively distinguish the Raman modes of two-dimensional (2D) layered materials by phonon symmetry. In this paper, we systematically investigated the phonon helicity selection of basal and edge planes of MoS2 bulk by HRRS. We find that the symmetry of the crystal structure changes the helicity selection of the E1g, E1 2g, and A1g modes in the edge plane. The theoretical calculation results confirm that the E1 2g and A1g modes of the basal plane exhibit a perfect helicity exchange, and the helicity selections of the E1 2g and A1g modes of the edge plane are eliminated or weakened. Our study provides references for phonon helicity selection of 2D layered materials represented by MoS2.

Upregulation of Biomarker Limd1 Was Correlated with Immune Infiltration in Doxorubicin-Related Cardiotoxicity.

Doxorubicin is one of the most common antitumor drugs. However, cardiotoxicity's side effect limits its clinical applicability. In the present study, Gene Expression Omnibus (GEO) datasets were applied to reanalyze differentially expressed genes (DEGs) and construct weighted correlation network analysis (WGCNA) modules of doxorubicin-induced cardiotoxicity in wild-type mice. Several other bioinformatics analyses were performed to pick out the hub gene, and then the correlation between the hub gene and immune infiltration was evaluated. In total, 120 DEGs were discovered in a mouse model of doxorubicin-induced cardiotoxicity, and PF-04217903, propranolol, azithromycin, etc. were found to be potential drugs against this pathological condition. Among all the DEGs, 14 were further screened out by WGCNA modules, of which Limd1 was upregulated and finally regarded as the hub gene after being validated in other GEO datasets. Limd1 was upregulated in the peripheral blood mononuclear cell (PBMC) of the rat model, and the area under curve (AUC) of the receiver operating characteristic curve (ROC) in diagnosing cardiotoxicity was 0.847. The GSEA and PPI networks revealed a potential immunocyte regulatory role of Limd1 in cardiotoxicity. The proportion of "dendritic cells activated" in the heart was significantly elevated, while "macrophage M1" and "monocytes" declined after in vivo doxorubicin application. Finally, Limd1 expression was significantly positively correlated with "dendritic cells activation' and negatively correlated with "monocytes" and "macrophages M1'. In summary, our results suggested that limd1 is a valuable biomarker and a potential inflammation regulator in doxorubicin-induced cardiotoxicity.

A predictive scoring system for postoperative delirium in the elderly patients with intertrochanteric fracture.

OBJECTIVE: To establish a scoring system to predict the postoperative delirium in elderly patients with intertrochanteric fracture. MATERIALS AND METHODS: We retrospectively reviewed 159 elderly patients with a diagnosis of intertrochanteric fracture and underwent closed reduction and intramedullary nail fixation, and then divided them into two groups including the delirium group (23 cases) or non-delirium group (136 cases) in our hospital from January 2017 to December 2019. The following clinical characteristics were recorded and analyzed: age, gender, fracture classification, body mass index (BMI), history of diabetes mellitus, history of stroke, preoperative albumin, preoperative hemoglobin (Hb), preoperative arterial partial pressure of oxygen (PaO2), time between admission and surgery, lower limb thrombosis, American Society of Anesthesiologists (ASA) grade, operative time, operative blood loss, and intraoperative blood transfusion. The prevalence of these clinical characteristics in delirium group was evaluated, and the scoring system was established using logistic regression analysis. The performance of the scoring system was also prospectively validated. RESULTS: The predictive scoring system was based on five clinical characteristics confirmed as significant predictors of postoperative delirium, namely, age > 75 years, history of stroke, preoperative Hb ≤ 100 g/L, preoperative PaO2 ≤ 60 mmHg, and time between admission to surgery > 3 days. Delirium group showed a significant higher score than non-delirium (6.26 vs. 2.29, P < 0.001), and the optimal cut-off value for the scoring system was 4 points. The sensitivity and specificity of the scoring system for predicting postoperative delirium were 82.61% and 81.62% in derivation set, respectively, and 72.71% and 75.00% in validation set. CONCLUSION: The predictive scoring system confirmed with achieve satisfactory sensitivity and specificity in predicting postoperative delirium in the elderly with intertrochanteric fracture. The risk of postoperative delirium in patients with the score of 5 to 11 is high, while the score of 0 to 4 is low.

Exploring the Role of TaPLC1-2B in Heat Tolerance at Seedling and Adult Stages of Wheat through Transcriptome Analysis.

Heat stress is a major abiotic stress that can cause serious losses of a crop. Our previous work identified a gene involved in heat stress tolerance in wheat, TaPLC1-2B. To further investigate its mechanisms, in the present study, TaPLC1-2B RNAi-silenced transgenic wheat and the wild type were comparatively analyzed at both the seedling and adult stages, with or without heat stress, using transcriptome sequencing. A total of 15,549 differentially expressed genes (DEGs) were identified at the adult stage and 20,535 DEGs were detected at the seedling stage. After heat stress, an enrichment of pathways such as phytohormones and mitogen-activated protein kinase signaling was mainly found in the seedling stage, and pathways related to metabolism, glycerophospholipid metabolism, circadian rhythms, and ABC transporter were enriched in the adult stage. Auxin and abscisic acid were downregulated in the seedling stage and vice versa in the adult stage; and the MYB, WRKY, and no apical meristem gene families were downregulated in the seedling stage in response to heat stress and upregulated in the adult stage in response to heat stress. This study deepens our understanding of the mechanisms of TaPLC1-2B in regard to heat stress in wheat at the seedling and adult stages.

[Research progress of brain-computer interface application paradigms based on rapid serial visual presentation].

Rapid serial visual presentation (RSVP) is a type of psychological visual stimulation experimental paradigm that requires participants to identify target stimuli presented continuously in a stream of stimuli composed of numbers, letters, words, images, and so on at the same spatial location, allowing them to discern a large amount of information in a short period of time. The RSVP-based brain-computer interface (BCI) can not only be widely used in scenarios such as assistive interaction and information reading, but also has the advantages of stability and high efficiency, which has become one of the common techniques for human-machine intelligence fusion. In recent years, brain-controlled spellers, image recognition and mind games are the most popular fields of RSVP-BCI research. Therefore, aiming to provide reference and new ideas for RSVP-BCI related research, this paper reviewed the paradigm design and system performance optimization of RSVP-BCI in these three fields. It also looks ahead to its potential applications in cutting-edge fields such as entertainment, clinical medicine, and special military operations.

Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy.

BACKGROUND: Hypertension-induced cardiac hypertrophy is one of the most common pre-conditions that accompanies heart failure. This study aimed to identify the key pathogenic genes in the disease process. METHODS: GSE18224 was re-analyzed and differentially expressed genes (DEGs) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. Networks of transcription factor (TF)-mRNA, microRNA (miRNA)-mRNA and Protein-Protein interaction (PPI) were constructed, and a key module was further screened out from PPI network. GSE36074 dataset and our transverse aortic constriction (TAC) mouse model were used to validate gene expression in the module. Finally, the correlation between the genes and biomarkers of cardiac hypertrophy were evaluated. RESULTS: Totally, there were 348 DEGs in GSE18224, which were mainly enriched in biological processes including collagen fibril organization, cellular response to transforming growth factor-beta stimulus and were involved in ECM-receptor interaction and Oxytocin signaling pathway. There were 387 miRNAs targeted by 257 DEGs, while 177 TFs targeted 71 DEGs. The PPI network contained 222 nodes and 770 edges, with 18 genes screened out into the module. After validation, 8 genes, which were also significantly upregulated in the GSE36074 dataset, were selected from the 18 DEGs. 2 of the 8 DEGs, including Eln and Tgfb3 were significantly upregulated in our mouse model of myocardial hypertrophy. Finally, the expression of Eln and Tgfb3 were found to be positively correlated with the level of the disease biomarkers. CONCLUSIONS: Upregulated key genes Eln and Tgfb3 were positively correlated with the severity of cardiac hypertrophy, which may provide potential therapeutic targets for the disease.

An intrinsic mechanism for coordinated production of the contact-dependent and contact-independent weapon systems in a soil bacterium.

Soil bacteria possess multiple weapons to fend off microbial competitors. Currently, we poorly understand the factors guiding bacterial decisions about weapon systems deployment. In this study, we investigated how such decisions are made by the soil bacterium Lysobacter enzymogenes, used in antifungal plant protection. We found that weapons production is guided by environmental cues. In rich media, which likely mimic environments crowded with other microbes, L. enzymogenes produces a contact-dependent weapon, type six secretion system (T6SS). In nutrient-poor media, likely dominated by filamentous oomycetes and fungi, L. enzymogenes synthesizes and secretes a heat-stable antifungal factor (HSAF), a contact-independent weapon. Surprisingly, the T6SS inner tube protein Hcp is accumulated intracellularly even in nutrient-poor media, when the T6SS is not assembled. We found that Hcp interacts with the transcription factor Clp required for activating HSAF biosynthesis operon expression. Hcp protects Clp from binding to c-di-GMP, an intracellular second messenger inhibiting DNA binding. The increased concentration of c-di-GMP-free Clp thus leads to higher gene expression and HSAF production. Therefore, when the contact-dependent weapon, T6SS, is not in use, accumulation of one of its structural components, Hcp, serves as a signal to enhance production of the contact-independent weapon, HSAF. The uncovered environment-dependent and auto-regulatory mechanisms shed light on the processes governing deployment of various weapon systems in environmental bacteria.

Optical characteristics of bilayer decoupling MoS2 grown by the CVD method.

Study of exciton recombination process is of great significance for the optoelectronic device applications of two-dimensional transition metal chalcogenides (TMDCs). This research investigated the decoupling MoS2 structures by photoluminescence (PL) measurements. First, PL intensity of the bilayer MoS2 (BLM) is about twice of that of the single layer MoS2 (SLM) at low temperature, indicating no transition from direct bandgap to indirect bandgap for BLM due to the decrease of interlayer coupling which can be shown by Raman spectra. Then, the localized exciton emission appears for SLM at 7 K but none for BLM, showing different exciton localization characteristics. The PL evolution with respect to the excitation intensity and the temperature further reveal the filling, interaction, and the redistribution among free exciton states and localized exciton states. These results provide very useful information for understanding the localized states and carrier dynamics in BLM and SLM.

Heterologous expression of the TaPI-PLC1-2B gene enhanced drought and salt tolerance in transgenic rice seedlings.

Drought and salt stress are important factors that affect plant growth and development and cause crop yield reductions worldwide. Phospholipase C is a class of enzymes that can hydrolyze phospholipids, and it has been shown to play an important role in plant growth regulation and stress response. We used rice as a model to investigate the function of the wheat TaPI-PLC1-2B gene in salt and drought tolerance. For this purpose, we heterologously expressed the TaPI-PLC1-2B gene in rice and studied the transcriptional differences in transgenic and wide-type rice plants in the presence and absence of drought and salt stress. Our results showed that 2130 and 1759 genes expressed differentially in the TaPI-PLC1-2B overexpression rice line under salt and drought stress, respectively. Gene ontology enrichment results showed that differentially expressed genes (DEGs) were significantly enriched in cellular process, metabolic process, stimulus-response, cell, organelle, catalytic activity, and other functional processes under salt and drought stress. In addition, the Kyoto Encyclopedia of Genes and Genomes pathway analysis showed DEG enrichment in plant-pathogen interaction, phosphoinositol, plant hormones, and other signaling pathways under the two stress treatments. Furthermore, the chromosomal localization of salt and drought stress-responsive DEGs showed a clear distribution pattern on specific rice chromosomes. For instance, the greatest number of drought stress-responsive genes mapped to rice chromosomes 1 and 6. The current analysis has built the basis for future explorations to decipher the TaPI-PLC1-2B-mediated plant stress response mechanism in the relatively challenging wheat system.

Effects of PCSK9 Inhibition on Coronary Atherosclerosis Regression of Nontarget Lesions after Primary Percutaneous Coronary Intervention in Acute Coronary Syndrome Patients.

Aims: To evaluate the regression of coronary atherosclerosis with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in acute coronary syndrome (ACS) patients following primary percutaneous coronary intervention (PPCI). Methods and Result. We examined 40 nontarget lesions in 17 ACS patients who underwent PPCI and were treated with PCSK9 inhibitors. At 1 year, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and atherogenic index (AI) decreased significantly by 2.5 mmol/L, 2.01 mmol/L, and 1.86, respectively. On quantitative coronary angiography, treatment with PCSK9 inhibitors reduced significantly the atherosclerotic area stenosis in nontarget lesions (61.18 ± 14.55 at baseline vs. 52.85 ± 15.51 at 1 year, P < 0.001). Conclusions: After 1 year of PCSK9 inhibition treatment for ACS patients, the area stenosis of non-TLR was considerably reduced.