Diabetes Mellitus and Gynecological and Inflammation Disorders Increased the Risk of Pregnancy Loss in a Population Study.

(1) Background: Diabetes mellitus (DM) induces oxidative stress and inflammation with negative effect on pregnancy outcomes. This study aimed to determine whether DM increases the risk of pregnancy loss and to identify other potential risk factors; (2) Methods: We identified female patients diagnosed with DM from 2000-2015 in the Taiwanese National Health Insurance Research Database according to the International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9 CM) code 250. The event was pregnancy loss, defined as ICD-9 CM codes 630-639, which was tracked until 31 December 2015. The control group included 4-fold more non-DM female patients who were matched for age and disease severity. Multivariate Cox regression was employed to determine the risk factors associated with pregnancy loss; (3) Results: The hazard ratio (HR) for the risk of pregnancy loss due to DM was 1.407 (95% confidence interval: 1.099-1.801, p = 0.007), and the risk factors for older age, gynecological disorders and inflammation disorders were included. (4) Conclusions: The study concluded that women with DM have a greater risk of experiencing pregnancy loss. Healthcare providers should proactively manage and educate diabetic patients to reduce their risk of pregnancy loss. Understanding other probable risk factors can help in developing targeted interventions and support systems for women to improve pregnancy outcomes.

Understanding Galectin-3's Role in Diastolic Dysfunction: A Contemporary Perspective.

Diastolic dysfunction, a prevalent condition characterized by impaired relaxation and filling of the left ventricle, significantly contributes to heart failure with preserved ejection fraction (HFpEF). Galectin-3, a ß-galactoside-binding lectin, has garnered attention as a potential biomarker and mediator of fibrosis and inflammation in cardiovascular diseases. This comprehensive review investigates the impact of galectin-3 on diastolic dysfunction. We explore its molecular mechanisms, including its involvement in cellular signaling pathways and interaction with components of the extracellular matrix. Evidence from both animal models and clinical studies elucidates galectin-3's role in cardiac remodeling, inflammation, and fibrosis, shedding light on the underlying pathophysiology of diastolic dysfunction. Additionally, we examine the diagnostic and therapeutic implications of galectin-3 in diastolic dysfunction, emphasizing its potential as both a biomarker and a therapeutic target. This review underscores the significance of comprehending galectin-3's role in diastolic dysfunction and its promise in enhancing diagnosis and treatment approaches for HFpEF patients.

Silica nanoparticle design for colorectal cancer treatment: Recent progress and clinical potential.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.

Understanding the molecular crossroads in acute liver failure: A pathway to new therapies.

In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a critical condition characterized by rapid hepatocellular injury and organ dysfunction, and it often necessitates liver transplant to ensure patient survival. Recent research has elucidated the involvement of distinct cell death pathways, namely ferroptosis and pyroptosis, in the pathogenesis of ALF. Ferroptosis is driven by iron-dependent lipid peroxidation, whereas pyroptosis is an inflammatory form of cell death; both pathways contribute to hepatocyte death and exacerbate tissue damage. This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF, highlighting the role of key regulators such as silent information regulator sirtuin 1. Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways. Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.

Clinical value identification of RDW on in-hospital death in unruptured abdominal aortic aneurysm.

This study aimed to identify highly valuable blood indicators for predicting the clinical outcomes of patients with aortic aneurysms (AA). Baseline data of 1180 patients and 16 blood indicators were obtained from the public Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. The association of blood indicators with 4 types of clinical outcomes was analyzed, and the prediction performance of core indicators on different outcomes was next evaluated. Then, we explored the detailed association between core indicators and key outcomes among subgroups. Finally, a machine learning model was established to improve the prediction performance. Generalized linear regression analysis indicated that only red cell volume distribution width (RDW) was commonly associated with 4 end-points including surgery requirement, ICU stay requirement, length of hospital stay, and in-hospital death (all P < .05). Further, RDW showed the best performance for predicting in-hospital death by receiver operating characteristic (ROC) analysis. The significant association between RDW and in-hospital death was then determined by 3 logistic regression models adjusting for different variables (all P < .05). Stratification analysis showed that their association was mainly observed in unruptured AA and abdominal AA (AAA, all P < .05). We subsequently established an RDW-based model for predicting the in-hospital death only in patients with unruptured AAA. The favorable prediction performance of the RDW-based model was verified in training, validation, and test sets. RDW was found to make the greatest contribution to in-hospital death within the model. RDW had favorable clinical value for predicting the in-hospital death of patients, especially in unruptured AAA.

Unveiling significant risk factors for intensive care unit-acquired weakness: Advancing preventive care.

In this editorial, we discuss an article titled, "Significant risk factors for intensive care unit-acquired weakness: A processing strategy based on repeated machine learning," published in a recent issue of the World Journal of Clinical Cases. Intensive care unit-acquired weakness (ICU-AW) is a debilitating condition that affects critically ill patients, with significant implications for patient outcomes and their quality of life. This study explored the use of artificial intelligence and machine learning techniques to predict ICU-AW occurrence and identify key risk factors. Data from a cohort of 1063 adult intensive care unit (ICU) patients were analyzed, with a particular emphasis on variables such as duration of ICU stay, duration of mechanical ventilation, doses of sedatives and vasopressors, and underlying comorbidities. A multilayer perceptron neural network model was developed, which exhibited a remarkable impressive prediction accuracy of 86.2% on the training set and 85.5% on the test set. The study highlights the importance of early prediction and intervention in mitigating ICU-AW risk and improving patient outcomes.

Tumor-intrinsic IFNα and CXCL10 are critical for immunotherapeutic efficacy by recruiting and activating T lymphocytes in tumor microenvironment.

Tumor immunotherapies targeting PD-(L)1 exhibit anti-tumor efficacy in only 10-30% of patients with various cancers. Literature has demonstrated that a "hot tumor" which contains high T lymphocytes in the tumor microenvironment exhibits a better response to immunotherapies than a "cold tumor." This study aimed to investigate whether tumor-intrinsic IFNα and CXCL10 determine the recruitment and activation of CD8+ T cells to become "hot tumor." In this study, we found that CXCL10 overexpressed in a variety of tumors including lung, colon, and liver tumors with a correlation with PD-L1. High PD-L1 and CXCL10 are associated with better survival rates in tumor patients receiving immunotherapies. IFNs-downstream transcriptional factor IRF-1 and STAT1 were correlated with PD-L1 and CXCL10 expression. We demonstrated that IRF-1 and STAT1 were both bound with the promoters of PD-L1 and CXCL10, sharing the same signaling pathway and determining IFNs-mediated PD-L1 and CXCL10 expression. In addition, IFNα significantly increased activation marker IFNγ in PBMCs, promoting M1 type monocyte differentiation, CD4+ T, and CD8+ T cell activation. Particularly, we found that CD8+ T lymphocytes abundantly expressed CXCR3, a receptor of CXCL10, by flow cytometry, indicating that tumor-intrinsic CXCL10 potentially recruited CD8+ T in tumor microenvironment. To demonstrate the hypothesis, immunotherapy-sensitive CT26 and immunotherapy-resistant LL/2 were used and we found that CT26 cells exhibited higher IFNα, IFNγ, CXCL10, and PD-L1 levels compared to LL/2, leading to higher IFNγ expression in mouse splenocytes. Moreover, we found that CD8+ T cells were recruited by CXCL10 in vitro, whereas SCH546738, an inhibitor of CXCR3, inhibited T cell migration and splenocytes-mediated anti-tumor effect. We then confirmed that CT26-derived tumor was sensitive to αPD-L1 immunotherapy and LL/2-tumor was resistant, whereas αPD-L1 significantly increased T lymphocyte activation marker CD107a in CT26-derived BALB/c mice. In conclusion, this study revealed that CXCL10 expression is correlated with PD-L1 in tumors, sharing the same signaling pathway and associating with better immunotherapeutic efficacy. Further evidence in the syngeneic tumor models demonstrated that immunotherapy-sensitive CT26 intrinsically exhibited higher IFNα and CXCL10 compared to immunotherapy-resistant LL/2 to recruit and activate CD8+ T cells in the tumor microenvironment, exhibiting "hot tumor" characteristic of sensitizing αPD-L1 immunotherapies.

MCA Parallel Anatomic Scanning MR Imaging-Guided Recanalization of a Chronic Occluded MCA by Endovascular Treatment.

Basi-parallel anatomic scanning has been widely used for assessing the vascular morphology of vertebral basilar arteries. Previous studies have demonstrated its efficacy in evaluating the morphology of the MCA, which we refer to as MCA parallel anatomic scanning MR imaging (MCPAS). In this study, we present our experience with the application of MCPAS in patients with MCA occlusion. Endovascular treatment was performed on the patients with intact MCA morphology visible in on MCPAS, with no intracranial hemorrhage, occlusion, or other complications observed. No severe stenosis or re-occlusion was observed at the 12-month postoperative follow-up. In conclusion, MCPAS is an effective method for assessing the outer contour of an occlusive MCA. Endovascular treatment can be considered a safe and efficient option for patients who show a favorable MCA through MCPAS assessment.

Copper-Catalyzed P-H Bond Functionalization to Construct Biaryl Phosphafluorene Oxides.

In this study, in the presence of a certain amount of cuprous chloride catalyst and the synergistic action of ligand and base, the P-H bond activation of secondary biarylphosphine oxides and the attack on the ß-site of orthoaryl groups were investigated. Phosphafluorene oxide was synthesized by C-H bond activation and an intramolecular dehydrogenation coupling reaction to construct a C-P bond. Subsequently, we conducted a control experiment and made reasonable speculations about its mechanism. In addition, the use of phosphafluorene as a ligand in some synthetic catalytic reactions has shown excellent results, demonstrating its excellent catalytic properties.

Synthesis of Diarylamines via Nitrosonium-Initiated C-N Bond Formation.

Electron-rich diarylamines, exemplified by anisole-derived amines, play pivotal roles in process chemistry, pharmaceuticals, and materials. In this study, homo-diarylamines were synthesized directly from the C-H activation of electron-rich arenes by sodium nitrate/trifluoroacetic acid and the successive treatment of iron powder. Mechanistic investigations reveal that nitrosoarene serves as the reaction intermediate, and the formation of the second C-N bond between the resulting nitrosoarene and electron-rich arene is catalyzed by the nitrosonium ion (NO+). Thus, hetero-diarylamines were synthesized using preformed nitrosoarenes and various electron-rich arenes. This reaction complements a range of cross-coupling reactions catalyzed by transition metal catalysts.

Deoxycholic acid inducing chronic atrophic gastritis with colonic mucosal lesion correlated to mucosal immune dysfunction in rats.

The present study aimed to explore the underlying mechanism of bile reflux-inducing chronic atrophic gastritis (CAG) with colonic mucosal lesion. The rat model of CAG with colonic mucosal lesion was induced by free-drinking 20 mmol/L sodium deoxycholate to simulate bile reflux and 2% cold sodium salicylate for 12 weeks. In comparison to the control group, the model rats had increased abundances of Bacteroidetes and Firmicutes but had decreased abundances of Proteobacteria and Fusobacterium. Several gut bacteria with bile acids transformation ability were enriched in the model group, such as Blautia, Phascolarctobacter, and Enterococcus. The cytotoxic deoxycholic acid and lithocholic acid were significantly increased in the model group. Transcriptome analysis of colonic tissues presented that the down-regulated genes enriched in T cell receptor signaling pathway, antigen processing and presentation, Th17 cell differentiation, Th1 and Th2 cell differentiation, and intestinal immune network for IgA production in the model group. These results suggest that bile reflux-inducing CAG with colonic mucosal lesion accompanied by gut dysbacteriosis, mucosal immunocompromise, and increased gene expressions related to repair of intestinal mucosal injury.

Esophageal cancer: A global challenge requiring tailored strategies.

In this editorial we comment on the article published in a recent issue of the World Journal of Gastrointestinal Oncology. Characterized by high mortality rates and geographical variations in its incidence, esophageal cancer poses a major global health challenge. This editorial article synthesizes insights from the review of esophageal cancer conducted by Qu et al, which highlights the importance of tailored screening and treatment strategies. Key themes include the effect of regional disparities on screening protocols, advancements in early detection methodologies, and therapeutic management disparities between different regions. By embracing personalized approaches grounded in regional nuances and technological innovation, the article advocates for comprehensive and collaborative efforts to improve patient outcomes in esophageal cancer care.

Repairing Interfacial Defects in Self-Assembled Monolayers for High-Efficiency Perovskite Solar Cells and Organic Photovoltaics through the SAM@Pseudo-Planar Monolayer Strategy.

Lately, carbazole-based self-assembled monolayers (SAMs) are widely employed as effective hole-selective layers (HSLs) in inverted perovskite solar cells (PSCs). Nevertheless, these SAMs tend to aggregate in solvents due to their amphiphilic nature, hindering the formation of a monolayer on the ITO substrate and impeding effective passivation of deep defects in the perovskites. In this study, a series of new SAMs including DPA-B-PY, CBZ-B-PY, POZ-B-PY, POZ-PY, POZ-T-PY, and POZ-BT-PY are synthesized, which are employed as interfacial repairers and coated atop CNph SAM to form a robust CNph SAM@pseudo-planar monolayer as HSL in efficient inverted PSCs. The CNph SAM@pseudo-planar monolayer strategy enables a well-aligned interface with perovskites, synergistically promoting perovskite crystal growth, improving charge extraction/transport, and minimizing nonradiative interfacial recombination loss. As a result, the POZ-BT-PY-modified PSC realizes an impressively enhanced solar efficiency of up to 24.45% together with a fill factor of 82.63%. Furthermore, a wide bandgap PSC achieving over 19% efficiency. Upon treatment with the CNph SAM@pseudo-planar monolayer, also demonstrates a non-fullerene organic photovoltaics (OPVs) based on the PM6:BTP-eC9 blend, which achieves an efficiency of 17.07%. Importantly, these modified PSCs and OPVs all show remarkably improved stability under various testing conditions compared to their control counterparts.

Wolbachia pipientis (Rickettsiales: Rickettsiaceae) mediated effects on the fitness and performance of Aedes aegypti (Diptera: Culicidae) under variable temperatures and initial larval densities.

Wolbachia pipientis (Hertig, 1936), also referred as Wolbachia, is a bacterium present across insect taxa, certain strains of which have been demonstrated to impact the fitness and capacity to transmit viruses in mosquitoes, particularly Aedes aegypti (Linnaeus, 1762). Most studies examine these impacts in limited sets of environmental regimes. Here we seek to understand the impacts of environmentally relevant conditions such as larval density, temperature, and their interaction on wAlbB-infected A. aegypti. Using a factorial design, we measured wAlbB stability (relative density, post-emergence in females, and in progeny), the ability for wAlbB to induce cytoplasmic incompatibility, and bacterial effects on mosquito fitness (fecundity, fertility, and body mass) and performance (adult survival and time to pupation) across 2 temperature regimes (fluctuating and constant) and 2 initial larval densities (low and high). Fluctuating daily regimes of temperature (27 to 40 °C) led to decreased post-emergence wAlbB density and increased wAlbB density in eggs compared to constant temperature (27 °C). An increased fecundity was found in wAlbB-carrying females reared at fluctuating temperatures compared to uninfected wild-type females. wAlbB-carrying adult females showed significantly increased survival than wild-type females. Contrarily, wAlbB-carrying adult males exhibited a significantly lower survival than wild-type males. We found differential effects of assessed treatments (Wolbachia infection status, temperature, and larval density) across mosquito sexes and life stages. Taken together, our results indicate that realistic conditions may not impact dramatically the stability of wAlbB infection in A. aegypti. Nonetheless, understanding the ecological consequence of A. aegypti-wAlbB interaction is complex due to life history tradeoffs under conditions faced by natural populations.

Predicting peak inundation depths with a physics informed machine learning model.

Timely, accurate, and reliable information is essential for decision-makers, emergency managers, and infrastructure operators during flood events. This study demonstrates that a proposed machine learning model, MaxFloodCast, trained on physics-based hydrodynamic simulations in Harris County, offers efficient and interpretable flood inundation depth predictions. Achieving an average R 2 of 0.949 and a Root Mean Square Error of 0.61 ft (0.19 m) on unseen data, it proves reliable in forecasting peak flood inundation depths. Validated against Hurricane Harvey and Tropical Storm Imelda, MaxFloodCast shows the potential in supporting near-time floodplain management and emergency operations. The model's interpretability aids decision-makers in offering critical information to inform flood mitigation strategies, to prioritize areas with critical facilities and to examine how rainfall in other watersheds influences flood exposure in one area. The MaxFloodCast model enables accurate and interpretable inundation depth predictions while significantly reducing computational time, thereby supporting emergency response efforts and flood risk management more effectively.

Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin Attenuates Sorafenib-Induced Myocardial Inflammation and Toxicity.

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

Impact of CYP2C19 metabolizer status on esophageal mucosal inflammation, acid exposure, and motility among patients on chronic proton-pump inhibitor therapy with refractory symptoms of gastroesophageal reflux disease.

Background: The extent of disease severity remains unclear among CYP2C19 rapid and ultra-rapid metabolizers with refractory symptoms of gastroesophageal reflux disease (GERD) on chronic proton-pump inhibitors (PPIs). Aims: To determine the impact of CYP2C19 metabolizer status in relation to chronic PPI therapy with a focus on the extent of esophageal inflammation, acid exposure, and motor function. Methods: This retrospective study included 54 patients with refractory GERD symptoms who underwent CYP2C19 genotyping for PPI metabolism, esophagogastroduodenoscopy, ambulatory pH study, and high-resolution esophageal manometry. Patients were divided into three groups: normal metabolizer (NM) group, intermediate metabolizer/poor metabolizer (IM/PM) group, and rapid metabolizer/ultra-rapid metabolizer (RM/UM) group. The Chi-square test was used to analyze categorical variables, and one-way ANOVA for comparing means. Results: Rapid metabolizer/ultra-rapid metabolizer (RM/UM) group more frequently had either Los Angeles grade C or D GERD (7/19, 36.8% vs 1/21, 4.8%, P = 0.011) and metaplasia of the esophagus (9/19, 47.4% vs 2/21, 9.5%, P = 0.007) when compared to the NM group. RM/UM group were more frequently offered dilatation for nonobstructive dysphagia (8/19, 42.1% vs 3/21, 14.3%, P = 0.049) and more exhibited a hypotensive lower esophageal sphincter (LES) resting pressure compared to the NM group (10/19, 52.6% vs 4/21, 19%, P = 0.026). All three groups exhibited comparable DeMeester scores when PPIs were discontinued 72 hours before the ambulatory pH study. Conclusion: CYP2C19 RMs and UMs on chronic PPI with refractory GERD symptoms exhibited greater esophageal mucosal inflammation, as observed both endoscopically and histologically, and more were found to have hypotensive LES resting pressures and more were offered esophageal dilatation.

Deep Learning-Based Prediction Model for the Cobb Angle in Adolescent Idiopathic Scoliosis Patients.

Scoliosis, characterized by spine deformity, is most common in adolescent idiopathic scoliosis (AIS). Manual Cobb angle measurement limitations underscore the need for automated tools. This study employed a vertebral landmark extraction method and Feedforward Neural Network (FNN) to predict scoliosis progression in 79 AIS patients. The novel intervertebral angles matrix format showcased results. The mean absolute error for the intervertebral angle progression was 1.5 degrees, while the Pearson correlation of the predicted Cobb angles was 0.86. The accuracy in classifying Cobb angles (<15°, 15-25°, 25-35°, 35-45°, >45°) was 0.85, with 0.65 sensitivity and 0.91 specificity. The FNN demonstrated superior accuracy, sensitivity, and specificity, aiding in tailored treatments for potential scoliosis progression. Addressing FNNs' over-fitting issue through strategies like "dropout" or regularization could further enhance their performance. This study presents a promising step towards automated scoliosis diagnosis and prognosis.

The Association between Cafestol and Cardiovascular Diseases: A Comprehensive Review.

Cafestol, a bioactive compound found in coffee, has attracted considerable attention due to its potential impact on cardiovascular health. This review aims to comprehensively explore the association between cafestol and cardiovascular diseases. We delve into the mechanisms through which cafestol influences lipid metabolism, inflammation, and endothelial function, all of which are pivotal in cardiovascular pathophysiology. Moreover, we meticulously analyze epidemiological studies and clinical trials to elucidate the relationship between cafestol and cardiovascular outcomes. Through a critical examination of existing literature, we aim to provide insights into the potential benefits and risks associated with cafestol concerning cardiovascular health.