Clinical characterization and founder effect analysis in Chinese amyotrophic lateral sclerosis patients with SOD1 common variants.

OBJECTIVE: In the Asian population, SOD1 variants are the most common cause of amyotrophic lateral sclerosis (ALS). To date, more than 200 variants have been reported in SOD1. This study aimed to summarize the genotype-phenotype correlation and determine whether the patients carrying common variants derive from a common ancestor. METHODS: A total of 103 sporadic ALS (SALS) and 11 familial ALS (FALS) probands were included and variants were screened by whole exome sequencing. Functional analyses were performed on fibroblasts derived from patients with SOD1 p.V48A and control. Haplotype analysis was performed in the probands with p.H47R or p.V48A and their familial members. RESULTS: A total of 25 SOD1 variants were identified in 44 probands, in which p.H47R, p.V48A and p.C112Y variants were the most common variants. 94.3% and 60% of patients with p.H47R or p.V48A had lower limb onset with predominant lower motor neurons (LMNs) involvement. Patients with p.H47R had a slow progression and prolonged survival time, while patients with p.V48A exhibited a duration of 2-5 years. Patients with p.C112Y variant showed remarkable phenotypic variation in age at onset and disease course. SOD1V48A fibroblasts showed mutant SOD1 aggregate formation, enhanced intracellular reactive oxygen species level, and decreased mitochondrial membrane potential compared to the control fibroblast. Haplotype analysis showed that seven families had two different haplotypes. p.H47R and p.V48A variants did not originate from a common founder. CONCLUSIONS: Our study expanded the understanding of the genotype-phenotype correlation of ALS with SOD1 variants and revealed that the common p.H47R or p.V48A variant did not have a founder effect.

In our ALS cohort, 44 ALS probands were identified with 25 SOD1 variants, of which p.H47R, p.V48A and p.C112Y variants were the most frequent. The genotype­phenotype relationship of patients with SOD1 p.H47R, p.V48A and p.C112Y patients were summarized.SOD1^V48A fibroblasts showed mutant SOD1 aggregate formation, enhanced intracellular reactive oxygen species level, and decreased mitochondrial membrane potential compared to the control fibroblast.Our study expanded the understanding of the genotype­phenotype correlation of ALS with SOD1 variants and showed the common variants p.H47R or p.V48A did not have a founder effect.

Top 100 cited articles related to EUS: A bibliometric analysis.

Background and Objectives: Citation analysis is a fundamental method in bibliometrics for quantifying the impact and contribution of articles on a specific biomedical field. The purpose of our study was to identify and analyze the top 100 cited articles in the field of EUS. Methods: All published articles in the field of EUS were searched by using "endoscopic ultrasound" and its synonyms as the search terms without time limit. The Institute for Scientific Information Web of Science Core database was searched to determine the citations. The top 100 cited articles were identified and further evaluated for characteristics including publication year, authors, journals, impact factor, countries, institutions, article type, topic term, and evidence grade, among others. Results: A total of 430 articles were cited more than 100 times. The 100 most-cited articles were published between 1988 and 2018, and the medium citation was 240.5 (104.25). The top 100 cited articles mainly focused on diagnostic performance (80%) and interventional therapy (20%). The numbers of articles studying the diagnostic accuracy of FNA (n = 29) and tumor diagnosis (n = 29) were the highest among research articles on FNA and EUS of diagnostic categories, and EUS transluminal drainage (n = 14) was the most frequently used EUS technique for therapy. The focus of the majority of the articles was on diseases of pancreas (n = 55), and among the 55 articles related to pancreatic diseases, pancreatic cancer (n = 17) and solid pancreatic masses (n = 13) were the most researched topics. In addition, we found that the proportions of diagnostic and treatment-related articles at different time periods have statistical significance (P < 0.05). Conclusions: Our analysis provides an insight into the top 100 articles in the field of EUS, revealing EUS-guided FNA, tumor staging, and transluminal drainage as the major advances in the past 35 years. Pancreatic diseases were the most researched, especially pancreatic cancer or solid pancreatic masses. Our research has found that the number of articles on the application of EUS treatment has significantly increased.

Additive-Free, In Situ Rapid Repair of Vacancies in Fe[Fe(CN)6] Electrodes for Efficient Capacitive Deionization.

Fe[Fe(CN)6] (FeHCF) is considered a promising material for capacitive deionization-desalination of saline wastewater due to its excellent structure. However, additives are usually introduced during the synthesis of FeHCF in order to avoid [Fe(CN)6]3- vacancy defects filled by ligand water, which can result in the appearance of harmful byproducts and additional water treatment costs. In this study, an additive-free in situ vacancy repair strategy is proposed for the rapid synthesis of high-quality FeHCF in a saturated K3Fe(CN)6 solution. During the process of synthesizing FeHCF in solution, a high concentration of [Fe(CN)6]3- is found to facilitate the binding of Fe3+ to [Fe(CN)6]3- and hinder the hydrolysis and coordination reaction of Fe3+. After undergoing repair, FeHCF4 demonstrates an increased capacity and highly reversible electrochemical performance due to the robust structure. When utilized as Faraday cathodes in hybrid capacitive deionization (HCDI) systems, FeHCF4 exhibits a higher salt removal capacity (65.67 mg g-1) and lower energy consumption (0.68 kWh kg-1-NaCl) compared to unrepaired FeHCF1, while still maintaining excellent cycling performance. This environmentally friendly approach of repairing vacancies serves as a source of inspiration for the advancement of high-performance Prussian Blue analogues as capacitive sodium-removing materials.

Identifying the optimal measurement timing and hemodynamic targets of portal pressure gradient after TIPS in patients with cirrhosis and variceal bleeding.

BACKGROUND & AIMS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) placement remain unclear. This study aimed to identify the ideal moment for hemodynamic measurements and the optimal target of PPG in patients undergoing covered TIPS for variceal bleeding. METHODS: Between May 2018 and December 2021, 466 consecutive patients with recurrent variceal bleeding treated with covered TIPS were prospectively included. Post-TIPS PPG was measured immediately (immediate PPG), 24-72 hours (early PPG), and again 1 month (late PPG) after TIPS placement. The agreement among PPGs measured at different time points was assessed by intra-class correlation coefficient (ICC) and Bland-Altman method. The unadjusted and confounder-adjusted effects of PPGs on clinical outcomes (portal hypertensive complications [PHCs], overt hepatic encephalopathy [OHE], further decompensation, and death) were assessed using Fine and Gray competing risk regression models. RESULTS: The agreement between early PPG and late PPG (ICC: 0.34) was better than that between immediate PPG and late PPG (ICC: 0.23, p <0.001). Early PPG revealed an excellent predictive value for PHCs (early PPG≥ vs. <12 mmHg: adjusted hazard ratio 2.17, 95% CI 1.33-3.55, p = 0.002) and OHE (0.40, 95% CI 0.17-0.91, p = 0.030), while immediate PPG did not. Late PPG showed a predictive value for PHC risk but not OHE. By targeting the lowest risk of further decompensation, we identified an optimal hemodynamic target with early PPG ranging from 11 to 14 mmHg that was associated with a decreased risk of OHE and effective prevention of PHC. CONCLUSIONS: PPG measured 24 to 72 hours after TIPS correlates with long-term PPG and clinical outcomes, and a hemodynamic target PPG of 11-14 mmHg is associated with reduced encephalopathy but not compromised clinical efficacy. IMPACT AND IMPLICATIONS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) remain unclear. Here we show that post-TIPS PPG measured at least 24 hours but not immediately after the procedure correlated with long-term PPG and clinical events. Thus, PPG measurements taken at least 24 hours after TIPS should be used to guide decision making in order to improve clinical outcomes. Targeting a post-TIPS PPG of 11-14 mmHg or a 20%-50% relative reduction from pre-TIPS baseline measured 24-72 hours after the procedure was associated with reduced encephalopathy but not compromised clinical efficacy. Thus, these criteria could be used to guide TIPS creation and revision in patients with cirrhosis and variceal bleeding undergoing covered TIPS. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, ID: NCT03590288.

Cochlear reimplantation outcomes over 20 years: Expertise in reimplantation surgery and auditory-speech rehabilitation.

OBJECTIVES: The aim of this study was to present an institution's experience with cochlear reimplantation (CRI), to assess surgical challenges and post-operative outcomes and to increase the success rate of CRI. STUDY DESIGN: Retrospective single-institution study. SETTING: Tertiary medical center. METHODS: We retrospectively evaluated data from 76 reimplantation cases treated in a tertiary center between 2001 and 2022. Clinical features including etiology of hearing loss, type of failure, surgical issues, and auditory speech performance were analyzed. Categorical Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) scores were used to evaluate pre- and post-CRI outcomes. RESULTS: The CRI population comprises of 7 patients from our institute,69 referred patients from other centers. Device failure was the most common reason (68/76, 89.5 %) for CRI; in addition, there were 7 medical failures and 1 had both soft device failure. Medical failures included flap rupture and device extrusion, magnet migration, auditory neuropathy, leukoencephalopathy, foreign-body residue and meningitis. In 21/76 patients, the electrode technology was upgraded. The mean time to failure was 0.58-13 years, with a mean of 4.97 years. The mean (± SD) CAP and SIR scores before and after CRI were 5.2 ± 1.2 versus 5.5 ± 1.1 and 3.4 ± 1.1 versus 3.5 ± 1.1, respectively. Performance was poor in six patients with severe cochlear malformation, auditory nerve dysplasia, leukoencephalopathy, and epilepsy. CONCLUSION: CRI surgery is a challenging but relatively safe procedure, and most reimplanted patients experience favorable postoperative outcomes. Medical complications and intracochlear damage are the main causes of poor postoperative results. Therefore, adequate preoperative preparation and atraumatic CRI should be carried out for optimal results.

Gastrodin exerts perioperative myocardial protection by improving mitophagy through the PINK1/Parkin pathway to reduce myocardial ischemia-reperfusion injury.

BACKGROUND: Although blood flow is restored after treatment of myocardial infarction (MI), myocardial ischemia and reperfusion (I/R) can cause cardiac injury, which is a leading cause of heart failure. Gastrodin (GAS) exerts protective effects against brain, heart, and kidney I/R. However, its pharmacological mechanism in myocardial I/R injury (MIRI) remains unclear. PURPOSE: GAS regulates autophagy in various diseases, such as acute hepatitis, vascular dementia, and stroke. We hypothesized that GAS could repair mitochondrial damage and regulate autophagy to protect against MIRI. STUDY DESIGN: Male C57BL/6 mice and H9C2 cells were subjected to I/R and hypoxia-reoxygenation (H/R) injury after GAS administration, respectively, to assess the impact of GAS on cardiomyocyte phenotypes, heart, and mitochondrial structure and function. The effect of GAS on cardiac function and mitochondrial structure in patients undergoing cardiac surgery has been observed in clinical practice. METHODS: The effects of GAS on cardiac structure and function, mitochondrial structure, and expression of related molecules in an animal model of MIRI were evaluated using immunohistochemical staining, enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy, western blotting, and gene sequencing. Its effects on the morphological, molecular, and functional phenotypes of cardiomyocytes undergoing H/R were observed using immunohistochemical staining, real-time quantitative PCR, and western blotting. RESULTS: GAS significantly reduces myocardial infarct size and improves cardiac function in MIRI mice in animal models and increases cardiomyocyte viability and reduces cardiomyocyte damage in cellular models. In clinical practice, myocardial injury was alleviated with better cardiac function in patients undergoing cardiac surgery after the application of GAS; improvements in mitochondria and autophagy activation were also observed. GAS primarily exerts cardioprotective effects through activation of the PINK1/Parkin pathway, which promotes mitochondrial autophagy to clear damaged mitochondria. CONCLUSION: GAS can promote mitophagy and preserve mitochondria through PINK1/Parkin, thus indicating its tremendous potential as an effective perioperative myocardial protective agent.

Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Cold sub-mucosal injection versus traditional cold snare polypectomy for diminutive and small colorectal polyps: A systematic review and meta-analysis.

BACKGROUND: The guidelines recommend conventional cold snare polypectomy (C-CSP) for diminutive and small colorectal polyps (≤ 10 mm). However, it remains unclear whether CSP with sub-mucosal injection (SI-CSP) achieves comparable efficacy to C-CSP for managing these lesions. This study compares SI-CSP with C-CSP for patients with diminutive and small colorectal polyps. METHODS: An electronic literature search was conducted to retrieve articles comparing resection outcomes between SI-CSP and C-CSP in diminutive and small colorectal polyps (registration number INPLASY2023100096). Our primary outcomes of interest were the complete resection rate (CRR), complications (namely immediate bleeding, delayed bleeding and perforation) and polypectomy time. Mean differences with 95% confidence intervals (CI) were employed for continuous variables, while odds ratios (OR) with 95% CI were calculated for categorical variables. Data was analyzed using a random effects model and the I2 test was utilized to assess heterogeneity. RESULTS: Eight studies involving 1470 patients with 2223 polyps were included in our analysis. The CRR was not significantly higher in the SI-CSP group, with an OR of 95% CI 0.50 (0.22, 1.15). The incidences of immediate bleeding (OR 95% CI 0.60 [0.26-1.40]) and delayed bleeding (OR 95% CI 0.88 [0.32-2.42]) did not differ significantly between the two groups. On average, the mean polypectomy time was 64.75 seconds shorter in the C-CSP group (95% CI, - 102.96 to - 26.53). Notably, no perforation events were reported in the included studies. CONCLUSIONS: The use of SI-CSP was not superior to C-CSP in managing diminutive and small colorectal polyps and the procedure required significantly more time.

Causal relationships between psychological disorders and functional gastrointestinal disorders: a bidirectional two-sample Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies have shown bidirectional associations between psychological disorders (e.g. depression and anxiety) and functional gastrointestinal disorders. However, whether the relationships are causal is uncertain. Here, we used a bidirectional two-sample Mendelian randomization method to investigate the association between psychological disorders and functional gastrointestinal disorders (FGIDs). METHODS: We obtained genome-wide association study summary statistics for two common psychological disorders: depression (170 756 cases) and anxiety (31 977 cases), as well as for three common FGIDs: functional dyspepsia with 6666 cases, constipation with 26 919 cases, and irritable bowel syndrome (IBS) with 7053 cases. These summary statistics were retrieved from several publicly available genome-wide association study databases. The inverse variance weighted method was used as the main Mendelian randomization method. RESULTS: Inverse variance weighted Mendelian randomization analyses showed statistically significant associations between genetically predicted depression and risk of functional dyspepsia [odds ratio (OR): 1.40, 95% confidence interval (CI): 1.08-1.82], constipation (OR: 1.28, 95% CI: 1.13-1.44), and IBS (OR: 1.51, 95% CI: 1.37-1.67). Genetically predicted anxiety was associated with a higher risk of IBS (OR: 1.13, 95% CI: 1.10-1.17) instead of functional dyspepsia and constipation. In addition, genetically predicted IBS instead of functional dyspepsia and constipation was associated with a higher risk of depression (OR: 1.33, 95% CI: 1.12-1.57) and anxiety (OR: 2.05, 95% CI: 1.05-4.03). CONCLUSION: Depression is a causal risk factor for three common FGIDs. A bidirectional causal relationship between IBS and anxiety or depression was also identified.

Mechanisms of denitrifying granular sludge disintegration and calcium ion-enhanced re-granulation in acidic wastewater treatment.

Granular sludge is an alternative technology for the direct treatment of acidic nitrate-containing wastewater. Rapid remediation of disintegrated granules is essential to achieve efficient nitrogen removal. In this study, denitrifying granules were inactivated and disintegrated when the influent nitrate-nitrogen concentration was elevated from 240 to 360 mg L-1 in acidic wastewater (pH = 4.1) in a sequencing batch reactor. Tightly bound extracellular polymeric substances (TB-EPS) decreased by 60%, and extracellular protein (PN) was the main component of the reduced EPS. The three-dimensional excitation emission matrices (3D-EEM) results confirmed that the PNs that decreased were mainly tryptophan-like, tyrosine-like, and aromatic. This study further confirmed that the decrease in PN was mainly from the destruction of C=O (amide I) and N-H functional groups. Overloading of nitrogen-inhibited denitrifying activity and the destruction and dissolution of TB-EPS by acidic pH were responsible for granule disintegration, with PNs playing a major role in maintaining granule stability. Based on this, new granules with an average particle size of 454.4 µm were formed after calcium chloride addition; EPS nearly doubled during granule formation with PN as the dominant component, accounting for 64.7-78.4% of the EPS. Atomic force microscopy (AFM) revealed that PN-PN adhesion increased by 1.6-4.9 times in the presence of calcium ions, accelerating the re-granulation of disintegrated particles. This study provides new insights into the disintegration and remediation of granular sludge under acidic conditions.

Enhancing precision of defect 3D reconstruction in metal ultrasonic testing through point cloud completion.

During the ultrasound multi-layer focused scanning inspection process, the sequential images characterizing the defect morphology suffer from inter-layer contour information loss, which causes a reduction in the accuracy of defect 3D reconstruction, subsequently leading to errors in the characterization of the defect size and morphology. In order to address the above issues, a new method based on the Attention-based Residual Completion Network (ARC) is proposed for ultrasonic point cloud completion to characterize metal defects. Firstly, the ARC network extracts global contour morphological features and local edge detail features from the ultrasonic point cloud through consecutive residual convolutions. Subsequently, the two sets of features are concatenated and finally fed into a decoder based on self-attention, realizing the reconstruction of lost contour information and enhancing the 3D reconstruction accuracy of defects. In the experiment, an ultrasonic microscope was used to inspect actual steel plates. The internal defects were then completed using the ARC network, and the completion results were compared with the metallographic images of the defects. The experiment results indicated that, after completion, the characterization accuracy of defect morphology and sizes is enhanced by an average of 10.31 %. The ARC network provides a novel method for high-precision 3D characterization of internal defects in metal materials.

Chromium Catalyzed Asymmetric Reformatsky Reaction.

This study describes an unprecedented chromium-catalyzed asymmetric Reformatsky reaction, enabling the synthesis of chiral ß-hydroxy carbonyl compounds from α-chlorinated or α-brominated esters and amides. By employing a chiral chromium/diarylamine bis(oxazoline) catalyst, we achieved relatively broad functional group tolerance. Distinct from known reports, the protocol operates under both classical and photoredox conditions, facilitated by the in situ formation of a nucleophilic chiral chromium intermediate through a radical-polar crossover mechanism. Preliminary mechanistic insights, supported by DFT calculations, identify the nucleophilic aldehyde addition as the key stereo-determining step. This approach not only overcomes the limitations of existing Reformatsky reactions but also provides a versatile strategy for accessing complex chiral molecules.

Efficient Functionalization of Organosulfones via Photoredox Catalysis: Direct Incorporation of α-Carbonyl Alkyl Side Chains into α-Allyl-ß-Ketosulfones.

A novel and efficient method for functionalizing organosulfones has been established, utilizing a visible-light-driven intermolecular radical cascade cyclization of α-allyl-ß-ketosulfones. This process employs fac-Ir(ppy)3 as the photoredox catalyst and α-carbonyl alkyl bromide as the oxidizing agent. Via this approach, the substrates experience intermolecular addition of α-carbonyl alkyl radicals to the alkene bonds, initiating a sequence of C-C bond formations that culminate in the production of organosulfone derivatives. Notably, this technique features gentle reaction conditions and an exceptional compatibility with a wide array of functional groups, making it a versatile and valuable addition to the field of organic synthesis.

Achievement of waste sludge deep dehydration under acidic conditions with polydimethyldiallylammonium chloride and ferric chloride: performance and mechanism.

The biological treatment of wastewater generates a substantial amount of waste sludge that requires dewatering before final disposal. Efficient sludge dewatering is essential to minimize storage and transportation costs. In this study, the sludge conditioners polydimethyldiallylammonium chloride (PDMDAAC) and ferric chloride (FeCl3) were sequentially dosed, and the pH was adjusted to 3. As a result, the sludge moisture content (MC) was reduced to 59.4%, achieving deep dewatering. After conditioning, the tightly bound extracellular polymeric substances (TB-EPS) were reduced from 34.5 to 10.2 mg g-1 VSS, with the majority of the reduced fractions being composed of protein (PN). In contrast, soluble EPS increased more than 8 times. Subsequent studies revealed that the decrease in PN from TB-EPS primarily involved tryptophan and tyrosine proteins, accompanied by a significant reduction in the N-H and C[double bond, length as m-dash]C absorption peaks. These results highlight the critical role of TB-EPS dissolution in achieving deep dehydration, with the N-H in PN was identified as the key group influencing sludge dewatering. Combined with the changes in sludge particle size and morphology, the dewatering mechanism can be summarized as follows: PDMDAAC dissolves TB-EPS, simultaneously disrupting the floc structure and refining the sludge. Subsequently, FeCl3 reconstructs these elements, forming larger particle sizes. Finally, hydrochloric acid reduces TB-EPS once again, releasing bound water. This study offers alternative methods and new insights for achieving deep dewatering of waste sludge.

Cytokine Storm Related to CD4+ T Cells in Influenza Virus-Associated Acute Necrotizing Encephalopathy.

Acute necrotizing encephalopathy (ANE) is a rare but deadly complication with an unclear pathogenesis. We aimed to elucidate the immune characteristics of H1N1 influenza virus-associated ANE (IANE) and provide a potential therapeutic approach for IANE. Seven pediatric cases from a concentrated outbreak of H1N1 influenza were included in this study. The patients' CD4+ T cells from peripheral blood decreased sharply in number but highly expressed Eomesodermin (Eomes), CD69 and PD-1, companied with extremely high levels of IL-6, IL-8 in the cerebrospinal fluid and plasma. Patient 2, who showed high fever and seizures and was admitted to the hospital very early in the disease course, received intravenous tocilizumab and subsequently showed a reduction in temperature and a stable conscious state 24 h later. In conclusion, a proinflammatory cytokine storm associated with activated CD4+ T cells may cause severe brain pathology in IANE. Tocilizumab may be helpful in treating IANE.

Streamlined Synthesis of Varied Heteroarene-Condensed Benzofuran Derivatives via [4 + 2] Annulation of Benzofuran-Derived Azadienes and N-Alkyl Quinolinium Salts.

Herein we have pioneered an innovative synthetic strategy for the efficient assembly of various heteroarene-condensed benzofuran derivatives, utilizing benzofuran-derived azadienes (BDAs) and quinolines as the starting materials. This method functions with transition-metal catalysis and uses cost-effective formic acid as the reducing agent. Mechanistic investigations indicate that this transformation would involve a [4 + 2] annulation cascade process. This approach demonstrates a high tolerance to various functional groups and yields excellent results.

Successful allogeneic fecal microbiota transplantation for severe diversion colitis: a case report.

Ileostomy diverts the flow of feces, which can result in malnutrition in the distal part of the intestine. The diversity of the gut microbiota consequently decreases, ultimately leading to intestinal dysbiosis and dysfunction. This condition can readily result in diversion colitis (DC). Potential treatment strategies include interventions targeting the gut microbiota. In this case study, we effectively treated a patient with severe DC by ileostomy and allogeneic fecal microbiota transplantation (FMT). A 69-year-old man presented with a perforated malignant tumor in the descending colon and an iliac abscess. He underwent laparoscopic radical sigmoid colon tumor resection and prophylactic ileostomy. Follow-up colonoscopy 3 months postoperatively revealed diffuse intestinal mucosal congestion and edema along with granular inflammatory follicular hyperplasia, leading to a diagnosis of severe DC. After two rounds of allogeneic FMT, both the intestinal mucosal bleeding and edema significantly improved, as did the diversity of the gut microbiota. The positive outcome of allogeneic FMT in this case highlights the potential advantages that this procedure can offer patients with DC. However, few studies have focused on allogeneic FMT, and more in-depth research is needed to gain a better understanding.

Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy.

RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.

Pre-emptive TIPS in high-risk acute variceal bleeding. An updated and revised individual patient data meta-analysis.

BACKGROUND AND AIMS: A previous individual patient data meta-analysis (IPD-MA) showed that compared with drugs+endoscopy, the placement of transjugular portosystemic shunt within 72 hours of admission (pre-emptive transjugular intrahepatic portosystemic shunt: p-TIPS) increases the survival of high-risk patients (Child-Pugh B+ active bleeding and Child-Pugh C<14 points) with cirrhosis and acute variceal bleeding. However, the previous IPD-MA was not a two-stage meta-analysis, did not consider the potential risk of selection bias of observational studies, and did not include the most recent randomized clinical trial. We performed an updated and revised IPD-MA to reassess the efficacy of p-TIPS, addressing all previous issues. APPROACH AND RESULTS: We included all studies from the previous IPD-MA and searched for other possible eligible publications until September 2022. We performed a two-stage IPD-MA of data from 8 studies (4 randomized clinical trials and 4 observational). In addition, we performed a sensitivity analysis excluding those patients dying up to the first 72 hours after admission in the Drugs+Endoscopy arms of the 4 observational studies. The primary end point was the effects of p-TIPS versus Drugs+Endoscopy on 1-year survival.We identified 1389 patients (342 p-TIPS and 1047 Drugs+Endoscopy). The two-stage IPD-MA showed that p-TIPS significantly reduced the mortality in the overall population (HR=0·43, 95% CI: 0.32-0.60, p <0.001. This effect was observed in both subgroups of patients with Child-Pugh. The sensitivity analysis confirmed the survival benefit of p-TIPS. CONCLUSIONS: The updated two-stage IPD-MA confirms the significant survival advantage of p-TIPS in high-risk patients with cirrhosis and acute variceal bleeding. As a result, we recommend p-TIPS as the preferred first-choice treatment for these patients.