A versatile SERS platform based on conductive MOF-enforced carbon paper for rapidly and sensitively monitoring diazepam in aquatic products.

Herein, a versatile surface enhanced Raman scattering (SERS) platform was firstly constructed by integrating conductive metal organic framework (CMOF) with controlled electrodeposition of Au nanoparticles (Au NPs) on flexible carbon paper (CP-CMOF@Au) for sensitively recognizing diazepam (DZP) in aquatic products. The CMOF not only provided a pre-concentration effect for boosting sensitivity, but also dramatically improved the intrinsic electrical conductivity contributing to homogeneous distribution of Au NPs and forming SERS-active "hot spot" with superior stability and reproducibility. Based on CP-CMOF@Au chip, DZP can be sensitively detected with low limit of detection of 0.64 ng mL-1 and wide linear detection range from 0.001 to 10 µg mL-1. Also, DZP in aquatic products can be collected and recognized using multiple approaches (drip coating, soaking and wiping) with excellent reusability and satisfactory recovery of 85.8-103.3%. This method would provide an ingenious SERS strategy for rapidly monitoring DZP in aquatic products with good practical applicability.

Elevated 2-oxoglutarate antagonizes DNA damage responses in cholangiocarcinoma chemotherapy through regulating aspartate beta-hydroxylase.

Cholangiocarcinoma (CCA) is resistant to systemic chemotherapies that kill malignant cells mainly through DNA damage responses (DDRs). Recent studies suggest that the involvement of 2-oxoglutarate (2-OG) dependent dioxygenases in DDRs may be associated with chemoresistance in malignancy, but how 2-OG impacts DDRs in CCA chemotherapy remains elusive. We examined serum 2-OG levels in CCA patients before receiving chemotherapy. CCA patients are classified as progressive disease (PD), partial response (PR), and stable disease (SD) after receiving chemotherapy. CCA patients classified as PD showed significantly higher serum 2-OG levels than those defined as SD and PR. Treating CCA cells with 2-OG reduced DDRs. Overexpression of full-length aspartate beta-hydroxylase (ASPH) could mimic the effects of 2-OG on DDRs, suggesting the important role of ASPH in chemoresistance. Indeed, the knockdown of ASPH improved chemotherapy in CCA cells. Targeting ASPH with a specific small molecule inhibitor also enhanced the effects of chemotherapy. Mechanistically, ASPH modulates DDRs by affecting ATM and ATR, two of the major regulators finely controlling DDRs. More importantly, targeting ASPH improved the therapeutic potential of chemotherapy in two preclinical CCA models. Our data suggested the impacts of elevated 2-OG and ASPH on chemoresistance through antagonizing DDRs. Targeting ASPH may enhance DDRs, improving chemotherapy in CCA patients.

Aggregation-induced emission enhancement of gold nanoclusters triggered by sodium heparin and its application in the detection of sodium heparin and alkaline amino acids.

This work first reported that sodium heparin could cause the aggregation-induced emission enhancement (AIEE) effect of GSH-AuNCs (Glutathione functionalized gold nanoclusters). While it was interestingly found that the addition of alkaline amino acids would greatly weaken this effect. Thus, fluorescent system was designed for the quantitative detection of sodium heparin and alkaline amino acids. Negatively charged sodium heparin would connect with GSH-AuNCs through electrostatic attraction, leading to a significant AIEE effect. Then alkaline amino acids would competitively bind with sodium heparin, causing this effect to almost disappear. The reasons were as follows: (I) The hydrogen bonding between sodium heparin and alkaline amino acids was much stronger than electrostatic force, causing GSH-AuNCs to be competitively replaced. (II) Alkaline amino acids and GSH-AuNCs were both positively charged and repelled each other. The presence of alkaline amino acids would hinder the AIEE effect. (III) AIEE effect was confirmed to have a close relationship with the pH value which could be greatly affected by alkaline amino acids. (Ⅳ) Not only the hydrogen bonding, the electrostatic force also existed between the alkaline amino acids and sodium heparin. All the above reasons worked together to weaken the AIEE effect of GSH-AuNCs triggered by sodium heparin. Finally, both sodium heparin and alkaline amino acids were accurately detected, showing good correlation coefficients of 0.99 with the LODs of 0.0100 mg/mL (sodium heparin), 1.05 µM (histidine), 3.38 µM (arginine) and 6.16 µM (lysine), respectively.

The water footprint of hydraulic fracturing for shale gas extraction in China.

The rapid expansion of shale gas extraction worldwide has raised significant concerns about its impact on water resources. China is expected to undergo a shale revolution following the U.S. Most of the information on water footprint of shale gas exploration and hydraulic fracturing has been focused on the U.S. Here, we addressed this knowledge gap by establishing a comprehensive database of shale gas extraction in China, utilizing operational data from over 90 % of shale gas wells across the country. We present systematic analysis of water usage and flowback and produced water (FP water) production from all the major shale gas fields in China. Between 2012 and 2022, a total of 2740 shale gas wells were hydraulically fractured in China, primarily located in Sichuan and Chongqing Province. About 113 million m3 water was used for hydraulic fracturing, resulting in a cumulative shale gas production of 116 billion m3. As of 2022, the annual water use for hydraulic fracturing exceeded 20 million m3, and the annual FP water production reached 8.56 million m3. Notably, 80 % ~ 90 % of the FP water has been reused for hydraulic fracturing since 2020, accounting for 29 % to 35 % of the annual water usage for hydraulic fracturing. Water use per well in China varies primarily between 21,730 m3 to 61,070 m3 per well, and water use per horizontal length ranges primarily between 20 m3/m and 35 m3/m. The average ultimate FP water production per well in China was estimated to be 22,460 m3. The water use intensity (WUI) for shale gas extraction in China mainly ranges from 7 to 25.4 L/GJ, which is significantly higher than that of the U.S. This disparity is largely due to the lower Estimated Ultimate Recovery (EUR) of shale gas wells in China. Despite the considerable water consumption during the hydraulic fracturing process, shale gas has a relatively low water footprint compared to other conventional energy resources in China. The Produced water intensity (PWI) for shale gas extraction in China ranges from 3.9 to 7.3 L/GJ, which is consistent with the previously reported PWI values for shale gas extraction in the U.S. This study predicts water usage and FP production spanning the period 2023 to 2050 under two scenarios to assess the potential impact of shale gas extraction on water resources in the Longmaxi shale region in Sichuan Basin. The first scenario assumed a constant drilling rate, while the second assumed a yearly 10 % increase in drilling rate. With an assumed FP water reuse rate of 85 % for hydraulic fracturing, the estimated annual freshwater consumption for the two scenarios is 10.4 million m3 and 163 million m3, respectively. This accounts for only 0.28‱ and 4.4‱ of the total annual surface water resources in Sichuan and Chongqing Province. Our findings suggest that freshwater usage for hydraulic fracturing in humid Southern China is small relative to available surface water resources. However, prospective large-scale shale gas extraction in other arid and semi-arid regions may enhance the regional water scarcity. It is necessary to develop new hydraulic fracturing technologies that can use saline groundwater or other types of marginal water, and explore alternative management and treatment strategies for FP water.

Single-worm quantitative proteomics reveals aging heterogeneity in isogenic Caenorhabditis elegans.

The heterogeneity of aging has been investigated at cellular and organic levels in the mouse model and human, but the exploration of aging heterogeneity at whole-organism level is lacking. C. elegans is an ideal model organism for studying this question as they are self-fertilized and cultured in the same chamber. Despite the tremendous progress made in single-cell proteomic analysis, there is few single-worm proteomics studies about aging. Here, we apply single-worm quantitative mass spectrometry to quantify the heterogenous proteomic changes during aging across individuals, a total of 3524 proteins from 157 C. eleagns individuals were quantified. A reconstructed C. elegans aging trajectory and proteomic landscape of fast-aging individuals were used to analyze the heterogeneity of C. elegans aging. We characterized inter-individual proteomic variation during aging and revealed contributing factors that distinguish fast-aging individuals from their siblings.

Risk factors for drug-related acute pancreatitis: an analysis of the FDA adverse event reporting system (FAERS).

Objective: While several drugs have been linked to acute pancreatitis (AP), the AP-related risk of most drugs remains unclear. This study investigated the risk factors for drug-induced AP by analyzing a large dataset from the FDA Adverse Event Reporting System (FAERS). Methods: The reporting odds ratios (ROR) were used to assess the reports of drug-induced AP from the first quarter of 2004 to the second quarter of 2022. Single-factor, LASSO, and multi-factor regression analysis were performed to explore drug-related AP-related risk factors. Bonferroni correction was applied for the multiple comparisons performed. Results: A total of 264 drugs associated with AP, including antineoplastic drugs (35/264), antidiabetic drugs (28/264), antibacterial drugs (24/264), immunomodulatory drugs (11/264), antipsychotic drugs (6/264), and other drugs (160/264) were retrieved. Multi-factor analysis showed that males, age 41-54 years old, and 36 drugs, including Tigecycline, were risk factors for drug-related AP. The median time to drug-related AP onset was 31 days (interquartile range [IQR] 7-102 days) and about 75% of adverse events occurred within 100 days. Conclusion: These findings may help clinicians to identify drug-related AP at the early stage and can be used to inform future studies of drug-related AP pathogenesis.

Protective effect of Tibetan medicine Qiwei Tiexie pills on liver injury induced by acetaminophen overdose: An integrated strategy of network pharmacology, metabolomics and transcriptomics.

BACKGROUND: Drug-induced liver injury, particularly from acetaminophen (APAP), has emerged as a significant public health concern. Unfortunately, there is currently no effective treatment strategy available. Qiwei Tiexie pills (QWTX), a traditional Tibetan medicine, have demonstrated considerable clinical efficacy in treating various liver diseases. Nevertheless, the protective effect of QWTX against drug-induced liver injury and its underlying mechanism remains poorly understood. PURPOSE: This study aimed to assess the therapeutic potential of QWTX, a Tibetan medicine, in an animal model of APAP-induced liver injury. Additionally, we sought to investigate the molecular mechanism through which QWTX exerts its effects. METHODS: We employed LC-MS and network pharmacology to predict the potential targets of QWTX in drug-induced liver injury. Subsequently, we employed HE staining, transcriptomics, metabolomics, and qRT-PCR to analyze the mechanism underlying QWTX treatment in drug-induced liver injury. RESULTS: Network pharmacology analysis revealed that the active components of QWTX are involved in inflammatory and drug metabolism-related pathways. In mouse models, pretreatment with QWTX effectively mitigated the elevated levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory factors (IL-1ß, IL-6, and TNF-α) induced by APAP overdose. Moreover, APAP inhibited 1459 differentially expressed genes (DEGs) and 874 differential accumulation metabolites (DAMs), while QWTX promoted their expression. Conversely, APAP promoted 874 genes and 119 metabolites, which were inhibited by QWTX. Further analysis demonstrated that QWTX ameliorated the metabolic disorders induced by APAP overdose and potentially exerted a protective effect by inhibiting the expression of critical genes in crucial inflammatory pathways. QWTX also up-regulated antioxidant enzymes, thereby mitigating the oxidative stress resulting from APAP overdose. CONCLUSION: QWTX treatment effectively protects against APAP-induced liver damage in mice. Transcriptomic and metabolomic analyses further revealed that QWTX ameliorated hepatic metabolic disorders induced by APAP overdose while significantly suppressing the inflammatory response and oxidative stress associated with drug-induced liver injury. This study provides a new insight into the treatment of drug-induced liver injury by the TCM system and provides a basis for the development of new therapies for drug-induced liver injury by QWTX and its active ingredients.

RVX-208, an inducer of Apolipoprotein A-I, inhibits the particle production of hepatitis B virus through activation of cGAS-STING pathway.

BACKGROUND: Previously, we have demonstrated that Apolipoprotein A-I (ApoA-I) could inhibit the secretion of Hepatitis B virus (HBV), suggesting that stimulation of ApoA-I may block particle production. In the present study, we evaluated the anti-HBV effect of RVX-208, a small-molecule stimulator of ApoA-I gene expression. METHODS: RVX-208 was used to treat HepG2.2.15 cell, a HepG2 derived cell line stably producing HBV virus. Real-time PCR was performed to examine the HBV DNA levels. Magnetic particles, which were coated with anti-HBS or anti-HBE antibody, were used to examine the HBsAg and HBeAg levels in the supernatant of cultured HepG2.2.15 cells in combination with the enzyme conjugates that were prepared with horseradish peroxidase labelled anti-HBS or anti-HBE antibody in a double antibody sandwich manner. RNA-seq, immunoblots and real-time PCR were used to analyze the functional mechanism of RVX-208. RESULTS: RVX-208 could elevate the ApoA-I protein levels in HepG2.2.15 cells. In the meantime, RVX-208 significantly repressed HBV DNA, HBsAg and HBeAg levels in the supernatants of HepG2.2.15 cells. RNA-seq data revealed that RVX-208 treatment not only affected the cholesterol metabolism, which is closely related to ApoA-I, but also regulated signalling pathways that are associated with antiviral immune response. Moreover, mechanistic studies demonstrated that RVX-208 could activate cGAS-STING pathway and upregulate the transcription of a series of interferons, pro-inflammatory cytokines and chemokines with antiviral potential that are at the downstream of cGAS-STING pathway. CONCLUSION: Our study demonstrated that RVX-208, an inducer of ApoA-I, could suppress HBV particle production through activation of cGAS-STING pathway.

Joint application of metagenomic next-generation sequencing and histopathological examination for the diagnosis of pulmonary infectious disease.

IMPORTANCE: The diagnosis of some pulmonary infectious diseases and their pathogens is very difficult. A more precise diagnosis of pulmonary infectious diseases can help clinicians use proper antibiotics as well as reduce the development of drug-resistant bacteria. In this study, we performed both mNGS and pathology on lung puncture biopsy tissue from patients and found that combined mNGS and histopathology testing was significantly more effective than histopathology testing alone in detecting infectious diseases and identifying infectious diseases. In addition, the combined approach improves the detection rate of pathogenic microorganisms in infectious diseases and can be used to guide precision clinical treatment.

Clinical Efficacy of Small Needle Knife Therapy on Stage I-II Frozen Shoulder.

Frozen shoulder is a kind of aseptic inflammatory disease of the shoulder caused by strain, trauma, and other reasons, resulting in shoulder joint pain and limited function. The protocol presented here demonstrates the operation of a small needle knife in treating frozen shoulders, including patient management, material preparation, positioning, operation, and postoperative care. The purpose of this protocol is to relieve the pain and functional limitations and improve the living ability of patients with frozen shoulders. In our study, 76 stage I-II frozen shoulder patients who met the inclusion criteria were randomly divided into a control group and a treatment group (n=38). Patients in the control group received functional exercise, while the treatment group received small needle knife therapy with functional exercise. The visual analogue scores (VAS), the Constant and Murley scores (CMS), and the thickness of the coracohumeral ligament (CHL) under ultrasound were evaluated. After small needle knife therapy, the VAS score was significantly lower in the treatment group (5.11 ± 0.89) than in the control group (5.49 ± 0.65; t=-2.065, p<0.05); the CMS score was significantly higher in the treatment group (64.72 ± 4.78) than in the control group (60.97 ± 6.00; t=2.947, p<0.05); the CHL thickness was significantly decreased in the treatment group (2.38 ± 0.36) than in the control group (2.57 ± 0.42; t=-2.117, p<0.05). These results indicate that the small needle knife significantly relieved the pain symptoms, improved the shoulder function, reduced the CHL thickness, and improved the quality of life and, therefore, had significant therapeutic efficacy in stage I-II frozen shoulder patients.

Sex- and age-specific associations between abdominal fat and non-alcoholic fatty liver disease: a prospective cohort study.

Obesity is closely related to non-alcoholic fatty liver disease (NAFLD). Although sex differences in body fat distribution have been well demonstrated, little is known about the sex-specific associations between adipose tissue and the development of NAFLD. Using community-based cohort data, we evaluated the associations between magnetic resonance imaging-quantified areas of abdominal adipose tissue, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and incident NAFLD in 2830 participants (1205 males and 1625 females) aged 55-70 years. During a 4.6-year median follow-up, the cumulative incidence rates of NAFLD increased with areas of VAT and SAT both in males and females. Further analyses showed that the abovementioned positive associations were stronger in males than in females, especially in participants under 60 years old. In contrast, these sex differences disappeared in those over 60 years old. Furthermore, the risk of developing NAFLD increased nonlinearly with increasing fat area in a sex-specific pattern. Additionally, sex-specific potential mediators, such as insulin resistance, lipid metabolism, inflammation, and adipokines, may exist in the associations between adipose tissue and NAFLD. This study showed that the associations between abdominal fat and the risk of NAFLD were stratified by sex and age, highlighting the potential need for sex- and age-specific management of NAFLD.

Single-cell RNA sequencing reveals the lineage of malignant epithelial cells and upregulation of TAGLN2 promotes peritoneal metastasis in gastric cancer

Background Peritoneal metastasis (PM) is an important factor contributing to poor prognosis in patients with gastric cancer (GC). Transcriptomic sequencing has been used to explore the molecular changes in metastatic cancers, but comparing the bulk RNA-sequencing data between primary tumors and metastases in PM studies is unreasonable due to the small proportion of tumor cells in PM tissues. Methods We performed single-cell RNA-sequencing analysis on four gastric adenocarcinoma specimens, including one primary tumor sample (PT), one adjacent nontumoral sample (PN), one peritoneal metastatic sample (MT) and one normal peritoneum sample (MN), from the same patient. Pseudotime trajectory analysis was used to display the process by which nonmalignant epithelial cells transform into tumor cells and then metastasize to the peritoneum. Finally, in vitro and in vivo assays were used to validate one of the selected genes that promote peritoneal metastasis. Results Single-cell RNA sequencing showed that a development curve was found from normal mucosa to tumor tissues and then into metastatic sites on peritoneum. TAGLN2 was found to trigger this metastasis process. The migration and invasion capability of GC cells were changed by downregulating and upregulating TAGLN2 expression. Mechanistically, TAGLN2 might modulate tumor metastasis via alterations in cell morphology and several signaling pathways, thus promoting epithelial–mesenchymal transition (EMT). Conclusions In summary, we identified and validated TAGLN2 as a novel gene involved in GC peritoneal metastasis. This study provided valuable insight into the mechanisms of GC metastasis and developed a potential therapeutic target to prevent GC cell dissemination (AU)

Functional analysis of ZmG6PE reveals its role in responses to low-phosphorus stress and regulation of grain yield in maize.

A previous metabolomic and genome-wide association analysis of maize screened a glucose-6-phosphate 1-epimerase (ZmG6PE) gene, which responds to low-phosphorus (LP) stress and regulates yield in maize's recombinant inbred lines (RILs). However, the relationship of ZmG6PE with phosphorus and yield remained elusive. This study aimed to elucidate the underlying response mechanism of the ZmG6PE gene to LP stress and its consequential impact on maize yield. The analysis indicated that ZmG6PE required the Aldose_epim conserved domain to maintain enzyme activity and localized in the nucleus and cell membrane. The zmg6pe mutants showed decreased biomass and sugar contents but had increased starch content in leaves under LP stress conditions. Combined transcriptome and metabolome analysis showed that LP stress activated plant immune regulation in response to the LP stress through carbon metabolism, amino acid metabolism, and fatty acid metabolism. Notably, LP stress significantly reduced the synthesis of glucose-1-phosphate, mannose-6-phosphate, and ß-alanine-related metabolites and changed the expression of related genes. ZmG6PE regulates LP stress by mediating the expression of ZmSPX6 and ZmPHT1.13. Overall, this study revealed that ZmG6PE affected the number of grains per ear, ear thickness, and ear weight under LP stress, indicating that ZmG6PE participates in the phosphate signaling pathway and affects maize yield-related traits through balancing carbohydrates homeostasis.

Large-scale production of MXenes as nanoknives for antibacterial application.

Antimicrobial resistance of existing antibacterial agents has become a pressing issue for human health and demands effective antimicrobials beyond conventional antibacterial mechanisms. Two-dimensional (2D) nanomaterials have attracted considerable interest for this purpose. However, obtaining a high yield of 2D nanomaterials with a designed morphology for effective antibacterial activity remains exceptionally challenging. In this study, an efficient one-step mechanical exfoliation (ECO-ME) method has been developed for rapidly preparing Ti3C2 MXenes with a concentration of up to 30 mg mL-1. This synthetic pathway involving mechanical force endows E-Ti3C2 MXene prepared by the ECO-ME method with numerous irregular sharp edges, resulting in a unique nanoknife effect that can successfully disrupt the bacterial cell wall, demonstrating better antibacterial activity than the MXenes prepared by conventional wet chemical etching methods. Overall, this study provides a simple and effective method for preparing MXenes on a large scale, and its antibacterial effects demonstrate great potential for E-Ti3C2 in environmental and biomedical applications.

Selinexor Synergistically Promotes the Antileukemia Activity of Venetoclax in Acute Myeloid Leukemia by Inhibiting Glycolytic Function and Downregulating the Expression of DNA Replication Genes.

Introduction: The BCL-2 inhibitor venetoclax has been widely used in the treatment of acute myeloid leukemia (AML); however, AML patients treated with venetoclax gradually develop resistance. The exportin-1 (XPO1) inhibitor selinexor can synergistically promote the antileukemia activity of venetoclax, but the mechanism remains unclear. Methods and Results: Annexin V/7-aminoactinomycin D assays were used to examine the effects of a combination of venetoclax and selinexor (VEN+SEL) on AML cell lines and primary AML cells. RNA sequencing and oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) determinations by a Seahorse XF analyzer were employed to investigate the molecular mechanism of the toxicity of the VEN+SEL combination to AML cells. The cytotoxicity of NK cell combined with VEN+SEL combination was assessed in vitro using flow cytometry. VEN+SEL enhanced the apoptosis of AML cells (KG-1A and THP-1) and primary AML samples in vitro. The ECAR and OCR results demonstrated that the VEN+SEL combination significantly inhibited glycolytic function. RNA sequencing of THP-1 cells demonstrated that DNA replication-related genes were downregulated after treatment with the VEN+SEL combination. Conclusion: This study indicated that selinexor can synergistically enhance the antileukemia activity of venetoclax in AML cells in vitro by inhibiting glycolytic function and downregulating DNA replication-related genes. Based on our experimental data, combining selinexor with venetoclax is an appropriate advanced treatment option for AML patients.

Magnetic Microrobots Fabricated by Photopolymerization and Assembly.

Magnetic soft microrobots have great potential to access narrow spaces and conduct multiple tasks in the biomedical field. Until now, drug delivery, microsurgery, disease diagnosis, and dredging the blocked blood vessel have been realized by magnetic soft microrobots in vivo or in vitro. However, as the tasks become more and more complex, more functional units have been embedded in the body of the developed magnetic microrobots. These magnetic soft microrobots with complex designed geometries, mechanisms, and magnetic orientation are now greatly challenging the fabrication of the magnetic microrobots. In this paper, we propose a new method combining photopolymerization and assembly for the fabrication of magnetic soft microrobots. Utilizing the micro-hand assembly system, magnetic modules with different shapes and materials are firstly arrayed with precise position and orientation control. Then, the developed photopolymerization system is employed to fix and link these modules with soft materials. Based on the proposed fabrication method, 3 kinds of soft magnetic microrobots were fabricated, and the fundamental locomotion was presented. We believe that the presented fabrication strategy could help accelerate the clinical application of magnetic microrobots.

Massive and efficient encapsulation of single cells in monodisperse droplets and collagen-alginate microgels using a microfluidic device.

Single-cell manipulation is the key foundation of life exploration at individual cell resolution. Constructing easy-to-use, high-throughput, and biomimetic manipulative tools for efficient single-cell operation is quite necessary. In this study, a facile and efficient encapsulation of single cells relying on the massive and controllable production of droplets and collagen-alginate microgels using a microfluidic device is presented. High monodispersity and geometric homogeneity of both droplet and microgel generation were experimentally demonstrated based on the well-investigated microfluidic fabricating procedure. The reliability of the microfluidic platform for controllable, high-throughput, and improved single-cell encapsulation in monodisperse droplets and microgels was also confirmed. A single-cell encapsulation rate of up to 33.6% was achieved based on the established microfluidic operation. The introduction of stromal material in droplets/microgels for encapsulation provided single cells an in vivo simulated microenvironment. The single-cell operation achievement offers a methodological approach for developing simple and miniaturized devices to perform single-cell manipulation and analysis in a high-throughput and microenvironment-biomimetic manner. We believe that it holds great potential for applications in precision medicine, cell microengineering, drug discovery, and biosensing.

Small but strong: the emerging role of small nucleolar RNA in cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading cause of mortality and disability worldwide. Numerous studies have demonstrated that non-coding RNAs (ncRNAs) play a primary role in CVD development. Therefore, studies on the mechanisms of ncRNAs are essential for further efforts to prevent and treat CVDs. Small nucleolar RNAs (snoRNAs) are a novel species of non-conventional ncRNAs that guide post-transcriptional modifications and the subsequent maturation of small nuclear RNA and ribosomal RNA. Evidently, snoRNAs are extensively expressed in human tissues and may regulate different illnesses. Particularly, as the next-generation sequencing techniques have progressed, snoRNAs have been shown to be differentially expressed in CVDs, suggesting that they may play a role in the occurrence and progression of cardiac illnesses. However, the molecular processes and signaling pathways underlying the function of snoRNAs remain unidentified. Therefore, it is of great value to comprehensively investigate the association between snoRNAs and CVDs. The aim of this review was to collate existing literature on the biogenesis, characteristics, and potential regulatory mechanisms of snoRNAs. In particular, we present a scientific update on these snoRNAs and their relevance to CVDs in an effort to cast new light on the functions of snoRNAs in the clinical diagnosis of CVDs.

Endoscopic transgastric fenestration versus percutaneous drainage for management of (peri)pancreatic fluid collections adjacent to gastric wall (with video).

BACKGROUND: Percutaneous drainage (PCD) and endoscopic approaches have largely replaced surgical drainage as the initial approach for (peri) pancreatic fluid collections (PFC)s, while complications associated with endoscopic stent implantation are common. AIM: To introduce a novel endoscopic therapy named endoscopic transgastric fenestration (ETGF), which involves resection of tissue by endoscopic accessory between gastric and PFCs without stent implantation, and to evaluate its efficacy and safety compared with PCD for the management of PFCs adjacent to the gastric wall. METHODS: Patients diagnosed with PFCs adjacent to the gastric wall and who subsequently received ETGF or PCD were restrospectively enrolled. Indications for intervention were consistent with related guidelines. We analyzed patients baseline characteristics, technical and clinical success rate, recurrence and reintervention rate, procedure-related complications and adverse events. RESULTS: Seventy-two eligible patients were retrospectively identified (ETGF = 34, PCD = 38) from October 2017 to May 2021. Patients in the ETGF group had a significantly higher clinical success rate than those in the PCD group (97.1 vs 76.3%, P = 0.01). There were no statistically significant differences regarding recurrence, reintervention and incidence of complication between the two groups. While long-term catheter drainage was very common in the PCD group. CONCLUSION: Compared with PCD, ETGF has a higher clinical success rate in the management of PFCs adjacent to the gastric wall. ETGF is an alternative effective strategy for the treatment of PFCs adjacent to the gastric wall.

Construction of diverse spirooxindoles via a domino reaction of arylamines, but-2-ynedioates and 3-hydroxy-3-(indol-3-yl)indolin-2-ones.

An iodine-promoted domino reaction of arylamines/benzylamines, dialkyl but-2-ynedioates and 3-hydroxy-3-(indol-3-yl)indolin-2-ones showed very interesting molecular diversity. The reaction in acetonitrile at 65 °C in the presence of 30% mmol I2 resulted in spiro[indoline-3,1'-pyrido[4,3-b]indoles] in satisfactory yields. When anilines without para-substituents were used in the reaction, a direct substitution of the hydroxyl group to 2-(phenylamino)maleate at the para-position of aniline gave chain products in good yields. Additionally, similar reactions with benzylamines not only gave spiro[indoline-3,1'-pyrido[4,3-b]indoles], but also afforded spiro[indoline-3,1'-pyrano[4,3-b]indol]-2-ones in lower yields. A plausible domino annulation mechanism was rationally proposed for the formation of different kinds of polycyclic compounds.