Cardiac-specific deletion of BRG1 ameliorates ventricular arrhythmia in mice with myocardial infarction.

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.

First Reports of Cladosporium tenuissimum Causing Leaf spots on Hydrangea macrophylla in Anhui province in China.

Forever Summer Hydrangea (Hydrangea macrophylla) is a common flowering plant in the Yangtze River Valley area of China, and it is widely cultivated globally (Chen et al. 2015). In July 2023, H. macrophylla leaves exhibiting visible diseased lesions were reported in a nursery in Wuhu, Anhui Province, China. The incidence reached 40% in a 0.2 ha area. The primary disease symptom was multiple irregular necrotic spots (0.5 to 1 mm in diameter) appearing on the leaves. These spots on the leaves were faded yellow around the perimeter and grayish brown in the center.). 15 leaf samples were sterilized with 75% alcohol and rinsed three times in sterile distilled water, then transferred to antibiotic-added potato dextrose agar (PDA) for incubation at 27°C. The colonies were fluffy, flocculent, or hairy, dark green, gray-green to gray-brown in color, and spreading or protruding punctate with a colorless halo on PDA. The conidiophores were brown to dark brown, smooth or rough surface, mostly unbranched, clearly differentiated, erect or curved. The conidia displayed a light brown to brown hue, lemon shape, fusiform, elongated ellipsoid or others with obvious spore markings and spore umbilicus. Genomic DNA was extracted from fungal colonies on infected leaves of three collections separately (Braun et al. 2003) and the internal transcribed spacer regions (ITS), actin (ACT) genes and partial translation elongation factor-l-alpha (EF) were amplified and sequenced using the primers ITS1/4 (Yin et al. 2012), ACT-512F/ACT-783R and EF 1-728F/986R (Carbone and Kohn 1999), respectively. DNA sequences of isolates were identical and deposited in GenBank (accession no. OR362754 for ITS, OR611929 for ACT and PP209106 for EF). The consensus sequences from ITS, EF and ACT showed 100%, 98.98% and 100% identical to Cladosporium strains (accession no. OQ186140.1, MT154169.1 and OL322092.1), respectively. To confirm the pathogenicity of the isolates, hydrangeas were planted in 15-cm pots containing commercial potting mix (one plant/pot). Three healthy plants were inoculated at the five to eight leaf stage by spraying 50 µL of the isolate conidial suspension (4 × 106 spores/mL) on healthy leaves. Three plants treated with sterile distilled water were used as controls. After inoculation, all plants were placed in a humidity chamber (>95% relative humidity, 26°C) for 48 h and then transferred to a greenhouse at 22/27°C. All inoculated leaves exhibited symptoms similar to those observed in the nursery 10 days after inoculation, while no symptoms were observed for control leaves. The fungus was re-isolated and confirmed to be C. tenuissimum. Based on the above morphological characterization and molecular identification, the causal agent for this leaf spot disease was identified as C. tenuissimum. Although C. tenuissimum has been reported to cause disease on H. paniculata in northern China (Li et al.2021), this is the first time that C. tenuissimum has been found on H. macrophylla in southern China. This new disease of H. macrophylla caused by C. tenuissimum is a threat to urban greening and is worth further investigation.

MiR-184 targeting FOXO1 regulates host-cell oxidative stress induced by Chlamydia psittaci via the Wnt/ß-catenin signaling pathway.

Chlamydia psittaci is a human pathogen that causes atypical pneumonia after zoonotic transmission. We confirmed that C. psittaci infection induces oxidative stress in human bronchial epithelial (HBEs) cells and explored how this is regulated through miR-184 and the Wnt/ß-catenin signaling pathway. miR-184 mimic, miR-184 inhibitor, FOXO1 siRNA, or negative control sequence was transfected into HBE cells cultured in serum-free medium using Lipofectamine 2000. Then, prior to the cells were infected with C. psittaci 6BC, and the cells were treated with or without 30 µM Wnt/ß-catenin inhibitor ICG-001. Quantification of reactive oxygen species, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione was carried out according to the manufacturer's protocol using a corresponding assay kit. The outcome of both protein and gene was measured by western blotting or real-time fluorescence quantitative PCR. In C. psittaci-infected HBE cells, miR-184 was upregulated, while one of its target genes, FOXO1, was downregulated. ROS and MDA levels increased, while SOD and GSH contents decreased after C. psittaci infection. When miR-184 expression was downregulated, the level of oxidative stress caused by C. psittaci infection was reduced, and the Wnt/ß-catenin signaling pathway was inhibited. The opposite results were seen when miR-184 mimic was used. Transfecting with FOXO1 siRNA reversed the effect of miR-184 inhibitor. Moreover, when the Wnt/ß-catenin-specific inhibitor ICG-001 was used, the level of oxidative stress induced by C. psittaci infection was significantly suppressed. miR-184 can target FOXO1 to promote oxidative stress in HBE cells following C. psittaci infection by activation of the Wnt/ß-catenin signaling pathway.

The efficacy and safety of endoscopic ultrasound-guided fine-needle biopsy in gallbladder masses.

BACKGROUND: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is a widely used modality for acquiring various target samples, but its efficacy in gallbladder masses is unknown. The aim of this retrospective study was to evaluate the efficacy and safety of EUS-FNB in patients with gallbladder masses. METHODS: The study samples were composed of patients from March 2015 to July 2019 who needed to identify the nature of gallbladder masses through EUS-FNB. The outcomes of this study were the adequacy of specimens, diagnostic yields, technical feasibility, and adverse events of the EUS-FNB in gallbladder masses. RESULTS: A total of 27 consecutive patients with a median age of 58 years were included in this study. The 22-gauge FNB needle was feasible in all lesions. The median follow-up period of the patients was 294 days. The specimens sufficient for diagnosis account for 89% (24/27) and 93% (25/27) in cytology and histology, respectively. The overall diagnostic yields for malignancy showed the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.45% [95% confidence interval (CI): 75.12%-99.76%], 100% (95% CI: 46.29%-100%), 100% (95% CI: 80.76%-100%), 83.33% (95% CI: 36.48%-99.12%), and 96.30% (95% CI: 80.20%-99.99%), respectively. The subgroup analysis revealed that FNB could obtain sufficient specimens and high diagnostic yields in both gallbladder mass < 20.5 mm group and ≥ 20.5 mm group. One patient experienced mild abdominal pain after the procedure and recovered within one day. CONCLUSIONS: EUS-FNB is a reasonable diagnostic tool for the pretreatment diagnosis of patients with gallbladder masses, especially for patients who may miss the opportunity of surgery and need sufficient specimens to identify the pathological type so as to determine chemotherapy regimens. Further large-scale studies are needed to confirm our conclusion.

A DNA Origami-Based Gene Editing System for Efficient Gene Therapy in Vivo.

DNA nanostructures have played an important role in the development of novel drug delivery systems. Herein, we report a DNA origami-based CRISPR/Cas9 gene editing system for efficient gene therapy in vivo. In our design, a PAM-rich region precisely organized on the surface of DNA origami can easily recruit and load sgRNA/Cas9 complex by PAM-guided assembly and pre-designed DNA/RNA hybridization. After loading the sgRNA/Cas9 complex, the DNA origami can be further rolled up by the locking strands with a disulfide bond. With the incorporation of DNA aptamer and influenza hemagglutinin (HA) peptide, the cargo-loaded DNA origami can realize the targeted delivery and effective endosomal escape. After reduction by GSH, the opened DNA origami can release the sgRNA/Cas9 complex by RNase H cleavage to achieve a pronounced gene editing of a tumor-associated gene for gene therapy in vivo. This rationally developed DNA origami-based gene editing system presents a new avenue for the development of gene therapy.

Chlamydia psittaci Induces Autophagy in Human Bronchial Epithelial Cells via PERK and IRE1α, but Not ATF6 Pathway.

Chlamydia psittaci is an important pathogen that causes chronic and atypical pneumonia in humans. Autophagy and the unfolded protein response (UPR) are important mechanisms for regulating the growth of infectious parasitic pathogens in living cells. Here, we explored whether C. psittaci infection induced autophagy via the UPR and the effect of these cellular responses on the survival and replication of C. psittaci in human bronchial epithelial cells (HBEs). Not only were the numbers of autophagosomes and the expression of LC3-II and Beclin1 increased following C. psittaci infection of HBEs, but also the expression of p62 (also called sequestosome-1) was downregulated. Moreover, after C. psittaci infection, the UPR and UPR sensors PERK/eIF2α and IRE1α/XBP1 were activated, but not the ATF6 pathway. When either Bip siRNA was used to block normal initiation of the UPR, or activation of the PERK and IER1α pathways was blocked with specific inhibitors GSK2606414 and 4µ8C, the level of autophagy caused by C. psittaci infection was significantly inhibited. Furthermore, blocking activation of the UPR and associated pathways significantly reduced the number of C. psittaci inclusions. Our research suggests that the UPR, via the PERK and IRE1α, but not ATF6 signaling pathways, regulates HBE-cell autophagy induced by C. psittaci infection and the replication of C. psittaci.

Inhibitory effect and mechanism of gelatin stabilized ferrous sulfide nanoparticles on porcine reproductive and respiratory syndrome virus.

BACKGROUND: The infection and spread of porcine reproductive and respiratory syndrome virus (PRRSV) pose a serious threat to the global pig industry, and inhibiting the viral infection process is a promising treatment strategy. Nanomaterials can interact with viruses and have attracted much attention due to their large specific surface area and unique physicochemical properties. Ferrous sulfide nanoparticles (FeS NPs) with the characteristics of high reactivity, large specific surface area, and low cost are widely applied to environmental remediation, catalysis, energy storage and medicine. However, there is no report on the application of FeS NPs in the antiviral field. In this study, gelatin stabilized FeS nanoparticles (Gel-FeS NPs) were large-scale synthesized rapidly by the one-pot method of co-precipitation of Fe2+ and S2‒. RESULTS: The prepared Gel-FeS NPs exhibited good stability and dispersibility with an average diameter of 47.3 nm. Additionally, they were characterized with good biocompatibility and high antiviral activity against PRRSV proliferation in the stages of adsorption, invasion, and replication. CONCLUSIONS: We reported for the first time the virucidal and antiviral activity of Gel-FeS NPs. The synthesized Gel-FeS NPs exhibited good dispersibility and biocompatibility as well as effective inhibition on PRRSV proliferation. Moreover, the Fe2+ released from degraded Gel-FeS NPs still displayed an antiviral effect, demonstrating the advantage of Gel-FeS NPs as an antiviral nanomaterial compared to other nanomaterials. This work highlighted the antiviral effect of Gel-FeS NPs and provided a new strategy for ferrous-based nanoparticles against PRRSV.

The roles of microRNAs played in lung diseases via regulating cell apoptosis.

MicroRNAs (miRNAs) are a type of endogenous non-coding short-chain RNA, which plays a crucial role in the regulation of many essential cellular functions, including cellular migration, proliferation, invasion, autophagy, oxidative stress, apoptosis, and differentiation. The lung can be damaged by pathogenic microorganisms, as well as physical or chemical factors. Research has confirmed that miRNAs and lung cell apoptosis can affect the development and progression of several lung diseases. This article reviews the role of miRNAs in the development of lung disease through regulating host cell apoptosis.

Comparison between modified wet suction and dry suction technique for endoscopic ultrasound-guided fine-needle biopsy in pancreatic solid lesions.

BACKGROUND AND AIM: Although endoscopic ultrasound-guided fine-needle biopsy is widely applied, there is no clear consensus on the optimal biopsy technique. We described a modified wet suction technique (MWEST) with the aim to compare the efficacy and safety between MWEST and the dry suction technique (DST). METHODS: In this prospective, randomized, crossover, single-blinded study, patients with suspected pancreatic malignancy were randomized to the DST (group A) or MWEST (group B) for the first pass, and the two techniques were performed alternately. The primary outcome was the comparison of specimen adequacy and diagnostic yield between the techniques. Secondary outcomes included the macroscopic visible core length, blood contamination of specimens, and adverse events of both techniques. RESULTS: From January 2019 to September 2019, 216 passes were performed in 50 patients. The specimen adequacy was significantly higher in "per-lesion" (P = 0.026), "per-pass" (cytology: P = 0.034; histology: P = 0.042), and first-pass analysis (P = 0.034) for MWEST than for DST. In diagnostic yield, MWEST showed significantly superior histological yield (P = 0.014) and first-pass analysis (κ: MWEST: 0.743 and DST: 0.519) compared with DST. The median macroscopic visible core lengths were 8 mm (interquartile range: 3.25-15 mm) and 10 mm (interquartile range: 5.25-15 mm) for DST and MWEST, respectively (P = 0.036). Blood contamination was significantly more serious in DST than in MWEST (cytology: P = 0.021; histology: P = 0.042). CONCLUSIONS: Endoscopic ultrasound-guided fine-needle biopsy with MWEST resulted in significantly better quality of specimen, histological, and first-pass diagnostic yields and comparable safety compared with the DST. MWEST is preferred for endoscopic ultrasound-guided fine-needle biopsy in pancreatic solid lesions.

Recent advances on aptamer-based biosensors for detection of pathogenic bacteria.

As a significant constituent in biosphere, bacteria have a great influence on human activity. The detection of pathogen bacteria is closely related to the human health. However, the traditional methods for detection of pathogenic bacteria are time-consuming and difficult for quantification, although they are practical and reliable. Therefore, novel strategies for rapid, sensitive, and cost-effective detection are in great demand. Aptamer is a kind of oligonucleotide that selected by repeated screening in vitro or systematic evolution of ligands by exponential enrichment (SELEX) technology. Over the past years, owing to high affinity and specificity of aptamers, a variety of aptamer-based biosensors have been designed and applied for pathogen detection. In this review, we have discussed the recent advances on the applications of aptamer-based biosensors in detection of pathogenic bacteria. In addition, we also point out some problems in current methods and look forward to the further development of aptamer-based biosensors for pathogen detection.

Glycyrrhizic-Acid-Based Carbon Dots with High Antiviral Activity by Multisite Inhibition Mechanisms.

With the gradual usage of carbon dots (CDs) in the area of antiviral research, attempts have been stepped up to develop new antiviral CDs with high biocompatibility and antiviral effects. In this study, a kind of highly biocompatible CDs (Gly-CDs) is synthesized from active ingredient (glycyrrhizic acid) of Chinese herbal medicine by a hydrothermal method. Using the porcine reproductive and respiratory syndrome virus (PRRSV) as a model, it is found that the Gly-CDs inhibit PRRSV proliferation by up to 5 orders of viral titers. Detailed investigations reveal that Gly-CDs can inhibit PRRSV invasion and replication, stimulate antiviral innate immune responses, and inhibit the accumulation of intracellular reactive oxygen species (ROS) caused by PRRSV infection. Proteomics analysis demonstrates that Gly-CDs can stimulate cells to regulate the expression of some host restriction factors, including DDX53 and NOS3, which are directly related to PRRSV proliferation. Moreover, it is found that Gly-CDs also remarkably suppress the propagation of other viruses, such as pseudorabies virus (PRV) and porcine epidemic diarrhea virus (PEDV), suggesting the broad antiviral activity of Gly-CDs. The integrated results demonstrate that Gly-CDs possess extraordinary antiviral activity with multisite inhibition mechanisms, providing a promising candidate for alternative therapy for PRRSV infection.

Risk Factors of Problem Gaming and Gambling in US Emerging Adult Non-Students: The Role of Loot Boxes, Microtransactions, and Risk-Taking.

Video gaming and gambling have increasingly converged with one another (e.g., social casino games). For emerging adults (18-25 years old), who are already at an elevated risk for addictive disorders, this overlap in these activities may increase the likelihood of problematic involvement. At the moment, Internet gaming disorder (IGD) is being considered as a future medical diagnosis by the American Psychiatric Association. Therefore, the purpose of this study was to examine the potential comorbidity between IGD and gambling disorder (GD) in emerging adults, as well as explore if problematic engagement in gaming and gambling may be explained by recent trends in video game microtransactions (e.g., loot boxes) and risk-taking behaviors. An online survey was completed by 300 emerging adult non-students (Mage = 22.79, 49% male) from across the United States. The results revealed that compared to non-gamers, problematic gamers were 6.45 times more likely to problem gamble and compared to non-gamblers, problem gamblers were 5.62 times more likely to problem game. Microtransactions were the major mechanism for the relationship between IGD and GD. Participants with higher severity levels of either disorder demonstrated a greater likelihood of purchasing microtransactions, in addition to displaying significantly less aversion towards several domains of risk-taking. These findings suggest that emerging adults with probable IGD or GD may share common risk factors and patterns of behavior that transdiagnostic treatment approaches may better serve than syndrome-specific models.

Application of Omics and Bioinformatics Tools in Streptococcus Research.

Researchers used to focus on analyzing single gene or protein expression of the microbes. But recently, genome, transcriptome, proteome and metabolome have gained more and more attention. Based on technologies of omics, including genomics, transcriptomics and metabolomics, a large quantity of information about cells, microbes and human, such as the information about phylogeny, virulence, antibiotic resistance and other aspects, has been revealed. Genus Streptococcus is one of the most invasive groups of bacteria that cause both human and animal diseases, threatening public health. In this review, we summarize the application of omics to analyze this genus-Streptococcus.

Predictive factors for complications associated with penetrated fish bones outside the upper gastrointestinal tract.

PURPOSE: To investigate predictive risk factors for complications associated with migrating fish bones in the surrounding tissue of upper gastrointestinal tract. METHODS: A retrospective analysis over 12 years was conducted of 45 cases of buried fish bones in the surrounding tissue of upper gastrointestinal tract with complications. Meanwhile, a control group, including 39 cases of prolonged buried fish bones in the surrounding tissue of upper gastrointestinal tract without complications, was set. Patient clinical data were collected and analyzed to predict the risk factors for complications. RESULTS: The results of Chi-square test and univariate analysis both showed a significant difference in length of fish bone (> 2 cm), a history of concurrent medical illness (diabetes mellitus and renal hypofunction), symptoms (medium or heavy pain and dysphagia), and duration of significant symptoms (> 7 days) between the complication group and non-complication group. Multivariate analysis further identified length (> 2 cm), diabetes mellitus, medium or heavy pain, dysphagia, and duration of significant symptoms (> 7 days) as independent risk factors for complications. CONCLUSIONS: The consequences of fish bones migrating outside the upper gastrointestinal tract are various in different people. Awareness should be raised when encountering a patient ingesting a long fish bone, having a history of diabetes mellitus, presenting with significant discomforts, or these discomforts lasting for a long time. This study will help practitioners counsel their patients on the risks and `benefits of surgery versus observation of this condition.

[Recent research advances of 1-deoxynojirimycin and its derivatives].

The 1-DNJ named 1-deoxynojirimycinis (2R,3R,4R,5S)-2-(hydroxymethyl) piperidine-3,4,5-triol, which is the nature active components existingin mulberryresources including leaves, stems, roots and silkworm larva, silkworm chrysalis, etc.The 1-deoxynojirimycin is a polyhydroxylated piperidine alkaloid, which was first found in Streptomyces as an antibiotic. Then the Japanese researchers isolated it from the mulberry root. 1-DNJ can inhibit postprandial hyperglycemia by suppressing intestinal alpha glucosidase. Therefore, 1-DNJ is often used to treat treating diabetes and complicating disease and to prevent obesity and weight-related disorders. With the development of the researches, 1-deoxynojirimycin and its derivtiv was discovered to possess anti-hyperglycemic, anti-virus, anti-tumor functions and so on. Therefore,based on our current studythe existing knowledge on source, technique preparation process, pharmacokinetics, bioactivties,and in silico target fishing of 1-DNJ were summarized, so that the researchers may use it to explore future perspective of research on 1-DNJ.

Prediction of Toxin Genes from Chinese Yellow Catfish Based on Transcriptomic and Proteomic Sequencing.

Fish venom remains a virtually untapped resource. There are so few fish toxin sequences for reference, which increases the difficulty to study toxins from venomous fish and to develop efficient and fast methods to dig out toxin genes or proteins. Here, we utilized Chinese yellow catfish (Pelteobagrus fulvidraco) as our research object, since it is a representative species in Siluriformes with its venom glands embedded in the pectoral and dorsal fins. In this study, we set up an in-house toxin database and a novel toxin-discovering protocol to dig out precise toxin genes by combination of transcriptomic and proteomic sequencing. Finally, we obtained 15 putative toxin proteins distributed in five groups, namely Veficolin, Ink toxin, Adamalysin, Za2G and CRISP toxin. It seems that we have developed a novel bioinformatics method, through which we could identify toxin proteins with high confidence. Meanwhile, these toxins can also be useful for comparative studies in other fish and development of potential drugs.

Preparation of multiwalled carbon nanotubes/hydroxyl-terminated silicone oil fiber and its application to analysis of crude oils.

A simple and efficient method to analyze the volatile and semivolatile organic compounds in crude oils has been developed based on direct immersion solid-phase microextraction coupled to comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (DI-SPME-GC × GC/TOFMS). A novel fiber, multiwalled carbon nanotubes/hydroxyl-terminated silicone oil (MWNTs-TSO-OH), was prepared by sol-gel technology. Using standard solutions, the extraction conditions were optimized such as extraction mode, extraction temperature, extraction time, and salts effect. With the optimized conditions, a real crude oil sample was extracted and then analyzed in detail. It shows that the proposed method is very effective in simultaneously analyzing the normal and branched alkanes, cycloalkanes, aromatic hydrocarbons, and biomarkers of crude oil such as steranes and terpanes. Furthermore, the method showed good linearity (r > 0.999), precision (RSD < 8%), and detection limits ranging from 0.2 to 1.6 ng/L.

Biological Effects and Biomedical Applications of Areca Nut and Its Extract.

The dried, mature fruit of the palm tree species Areca catechu L. is known as the areca nut (AN) or betel nut. It is widely cultivated in the tropical regions. In many nations, AN is utilized for traditional herbal treatments or social activities. AN has historically been used to address various health issues, such as diarrhea, arthritis, dyspepsia, malaria, and so on. In this review, we have conducted a comprehensive summary of the biological effects and biomedical applications of AN and its extracts. Initially, we provided an overview of the constituents in AN extract. Subsequently, we summarized the biological effects of AN and its extracts on the digestive system, nervous system, and circulatory system. And we elucidated the contributions of AN and its extracts in antidepressant, anti-inflammatory, antioxidant, and antibacterial applications. Finally, we have discussed the challenges and future perspectives regarding the utilization of AN and its extracts as emerging pharmaceuticals or valuable adjuncts within the pharmaceutical field.