Using a monotonic density ratio model to increase the power of the goodness-of-fit test for logistic regression models with case-control data.

Logistic regression models are widely used in case-control data analysis, and testing the goodness-of-fit of their parametric model assumption is a fundamental research problem. In this article, we propose to enhance the power of the goodness-of-fit test by exploiting a monotonic density ratio model, in which the ratio of case and control densities is assumed to be a monotone function. We show that such a monotonic density ratio model is naturally induced by the retrospective case-control sampling design under the alternative hypothesis. The pool-adjacent-violator algorithm is adapted to solve for the constrained nonparametric maximum likelihood estimator under the alternative hypothesis. By measuring the discrepancy between this estimator and the semiparametric maximum likelihood estimator under the null hypothesis, we develop a new Kolmogorov-Smirnov-type statistic to test the goodness-of-fit for logistic regression models with case-control data. A bootstrap resampling procedure is suggested to approximate the p $$ p $$ -value of the proposed test. Simulation results show that the type I error of the proposed test is well controlled and the power improvement is substantial in many cases. Three real data applications are also included for illustration.

Classification of variant portal vein anatomy based on three-dimensional CT: surgical implications.

PURPOSES: The purpose of this study was to develop a new and more comprehensive classification system for portal vein (PV) variations using three-dimensional visualization and evaluation (3DVE) and to discuss the prevalence rates and clinical implications of the variants. METHODS: The anatomies of PVs were tracked and analyzed by using three-dimensional visualization of CT images acquired between 2013 and 2022. Scans from 200 adults were evaluated and a total of 178 patients (N = 178) were included in the study. The new classification system, named BLB classification, was developed based on the level of the absent PV branch in each variant anatomy. RESULTS: Using the BLB classification system, PVs were divided into thirteen subtypes. Only 82.6-84.8% of the portal veins of the 178 patients were depicted in Atri's, Cheng's or Covey's classification, compared with 100% identified by the BLB classification. The BLB classification was validated against external data sets from previous studies, with 97.0-98.9% of patients classified by the BLB system. CONCLUSION: Variant PV anatomies are more commonly seen based on 3DVE than in previous reports. The BLB classification covers almost all portal vein variants and may be used for planning liver surgery.

Inhibition of ALG3 stimulates cancer cell immunogenic ferroptosis to potentiate immunotherapy.

Immune checkpoint blockade therapy has drastically improved the prognosis of certain advanced-stage cancers. However, low response rates and immune-related adverse events remain important limitations. Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. Taken together, we reveal an unappreciated role of ALG3 in regulating tumor immunogenicity and propose a potential therapeutic strategy for enhancing cancer immunotherapy.

Identification of BRAF, CCND1, and MYC mutations in a patient with multiple primary malignant tumors: a case report and review of the literature.

BACKGROUND: Multiple primary malignant tumors (MPMTs), usually associated with worse malignant behavior and prognosis comparing to a single primary tumor, and have recently been found to have an increasing incidence globally. However, the pathogenesis of MPMTs remains to be clarified. Here, we report a unique case of the coexistence of malignant melanoma (MM), papillary thyroid carcinoma (PTC), and clear-cell renal cell carcinoma (ccRCC) along with our perceptions on its pathogenesis. CASE PRESENTATION: The case reported is of a 59-year-old male patient with unilateral nasal obstruction as well as a renal occupying lesion. Positron emission tomography-computed tomography (PET-CT) revealed a palpable mass of 32 × 30 mm on the posterior and left walls of the nasopharynx. In addition, an isodense nodule was observed in the right superior renal pole, approximately 25 mm in diameter, as well as a slightly hypodense shadow in the right leaf of the thyroid, approximately 13 mm in diameter. Nasal endoscopy and magnetic resonance imaging (MRI) confirmed the existence of a nasopharyngeal neoplasm. Afterward, biopsies of the nasopharyngeal neoplasm, thyroid gland and kidney were performed, and the patient was diagnosed with MM, PTC, and ccRCC according to the pathological and immunohistochemical results. Moreover, mutation of BRAFV600E was detected in bilateral thyroid tissues, and amplification of both CCND1 and MYC oncogenes were detected in the nasopharyngeal melanoma. After chemotherapy, the patient is now in good overall condition. CONCLUSIONS: This is the first reported case of a patient with the co-existence of MM, PTC and ccRCC undergoing chemotherapy with a favorable prognosis. Herein, we suggest that such a combination may be non-random, as for mutation of BRAFV600E might account for the co-occurrence of PTC and MM, while mutations of CCND1 and MYC cause the coexistence of MM and ccRCC. This finding may provide valuable guidance on the diagnosis and treatment of such disease, as well as the prevention of developing a second or third tumor for patients with a single primary.

Local Bearing Estimation for a Swarm of Low-Cost Miniature Robots.

Swarm robotics focuses on decentralised control of large numbers of simple robots with limited capabilities. Decentralised control in a swarm system requires a reliable communication link between the individuals that is able to provide linear and angular distances between the individuals-Range & Bearing. This study presents the development of an open-source, low-cost communication module which can be attached to miniature sized robots; e.g., Mona. In this study, we only focused on bearing estimation to mathematically model the bearings of neighbouring robots through systematic experiments using real robots. In addition, the model parameters were optimised using a genetic algorithm to provide a reliable and precise model that can be applied for all robots in a swarm. For further investigation and improvement of the system, an additional layer of optimisation on the hardware layout was implemented. The results from the optimisation suggested a new arrangement of the sensors with slight angular displacements on the developed board. The precision of bearing was significantly improved by optimising in both software level and re-arrangement of the sensors' positions on the hardware layout.

Involvement of LaeA in the regulation of conidia production and stress responses in Penicillium digitatum.

Involvement of LaeA in various biological processes of filamentous fungi has been demonstrated. However, its role in Penicillium digitatum, the causal agent of citrus postharvest green mold, remains unclear. In this study, a ΔPdLaeA mutant was constructed using homologous recombination. The production of conidia by the ΔPdLaeA mutant was reduced by half compared with that of the wild-type strain. The sensitivity of the ΔPdLaeA mutant increased under alkaline conditions. The virulence assay revealed that PdLaeA was dispensable for the virulence of P. digitatum. Comparative transcriptome analysis revealed that the function loss of PdLaeA resulted in the reduced expression of several secondary metabolite gene clusters. In addition, expression of several key regulators of conidiation (BrlA, FlbA, FlbC, FlbD, and FluG) was also downregulated in the ΔPdLaeA mutant. In summary, the present work demonstrated that PdLaeA was involved in the regulation of SM biosynthesis, as well as the development and environmental adaptation of P. digitatum.

Risks of developing breast and colorectal cancer in association with incomes and geographic locations in Texas: a retrospective cohort study.

BACKGROUND: No study has been conducted to investigate the spatial pattern and association of socioeconomic status (such as income) with breast and colorectal cancer incidence in Texas, United States. This study aimed to determine whether median household income was associated with the risk of developing breast and colorectal cancer in Texas and to identify higher cancer risks by race/ethnicity and geographic areas. METHODS: This was a retrospective cohort study with an ecological component in using aggregated measures at the county level. We identified 243,677 women with breast cancer and 155,534 men and women with colorectal cancer residing in 254 counties in Texas in 1995-2011 from the public-use dataset of Texas Cancer Registry. The denominator population and median household income at the county level was obtained from the U.S. Bureau of the Census. Cancer incidence rates were calculated as number of cases per 100,000 persons and age-adjusted using the 2000 US population data. We used the ArcGIS v10.1 (geographic information system software) to identify multiple clustered counties with high and low cancer incidences in Texas. RESULTS: Age-adjusted breast cancer incidence rate in the highest median income quintile group was 151.51 cases per 100,000 in 2008-2011 as compared to 98.95 cases per 100,000 in the lowest median income quintile group. The risk of colorectal cancer appeared to decrease with increasing median income in racial/ethnic population. Spatial analysis revealed the significant low breast cancer incidence cluster regions located in southwest US-Mexico border counties in Texas. CONCLUSIONS: This study demonstrated that higher income was associated with an increased risk of breast cancer and a decreased risk of colorectal cancer in Texas. There were geographic variations with cancer incidence clustered in high risk areas in Texas. Future studies may need to explore more factors that might explain income and cancer risk associations and their geographic variations.

Overexpression of Plakophilin2 Mitigates Capillary Leak Syndrome in Severe Acute Pancreatitis by Activating the p38/MAPK Signaling Pathway.

Purpose: Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS is of clinical importance for enhancing the prognosis of SAP. Plakophilin2 (PKP2), an essential constituent of desmosomes, plays a critical role in promoting connections between epithelial cells. However, the function and mechanism of PKP2 in CLS in SAP are not clear at present. Methods: We detected the expression of PKP2 in mice pancreatic tissue by transcriptome sequencing and bioinformatics analysis. PKP2 was overexpressed and knocked down to assess its influence on cell permeability, the cytoskeleton, tight junction molecules, cell adhesion junction molecules, and associated pathways. Results: PKP2 expression was increased in the pancreatic tissues of SAP mice and human umbilical vein endothelial cells (HUVECs) after lipopolysaccharide (LPS) stimulation. PKP2 overexpression not only reduced endothelial cell permeability but also improved cytoskeleton relaxation in response to acute inflammatory stimulation. PKP2 overexpression increased levels of ZO-1, occludin, claudin1, ß-catenin, and connexin43. The overexpression of PKP2 in LPS-induced HUVECs counteracted the inhibitory effect of SB203580 (a p38/MAPK signaling pathway inhibitor) on the p38/MAPK signaling pathway, thereby restoring the levels of ZO-1, ß-catenin, and claudin1. Additionally, PKP2 suppression eliminated the enhanced levels of ZO-1, ß-catenin, occludin, and claudin1 induced by dehydrocorydaline. We predicted that the upstream transcription factor PPARγregulates PKP2 expression, and our findings demonstrate that the PPARγactivator rosiglitazone significantly upregulates PKP2, whereas its antagonist GW9662 down-regulates PKP2. Administration of rosiglitazone significantly reduced the increase in HUVECs permeability stimulated by LPS. Conversely, PKP2 overexpression counteracted the GW9662-induced reduction in ZO-1, phosphorylated p38/p38, and claudin1. Conclusion: The activation of the p38/MAPK signaling pathway by PKP2 mitigates CLS in SAP. PPARγactivator rosiglitazone can up-regulate PKP2. Overall, directing efforts toward PKP2 could prove to be a feasible treatment approach for effectively managing CLS in SAP.

Effect of hydrothermal pH values on the morphology of special microspheres of lignin-based porous carbon and the mechanism of carbon dioxide adsorption.

The study reports the economic and sustainable syntheses of a lignin-based porous carbon (LPC) for CO2 capture application. The pH values of hydrothermal solution affected the polymerization and aromatization of spheroidization, with morphological changes from blocky to microsphere. In addition, the reliable mechanisms of CO2 adsorption were proposed by combining experiments with Gaussian16 simulations based on DFT. The electrostatic attraction of oxygen-containing functional groups and the diffusivity resistance of CO2 in the pores are the key factors for the CO2 adsorption. ​The carboxyl groups have the strongest electrostatic attraction to CO2. LPC-pH 1 has the highest carboxyl group content, possessing a CO2 adsorption capacity of up to 5.10 mmol/g at 0℃, 1 bar. Furthermore, CO2 diffusion resistance became a main factor as the adsorption temperature increases. The innovative combination of quantum chemical calculations and microscopic properties provides a viable pathway for an insight into the future control of lignin-based carbon formation.

Design and Fabrication of a C-Band Patch Antenna with Low Loss BaM4Si5O17 Microwave Dielectric Ceramics.

Single-phase BaM4Si5O17 (M = Yb, Er, Y, Ho) ceramics have been investigated for their crystal structures, microwave dielectric properties, flexural strength, and potential applications in dielectric antennas. Rietveld refinement and TEM analysis revealed that the BaM4Si5O17 ceramics exhibit a monoclinic structure (space groups: P21/m). The εr of the BaM4Si5O17 ceramics was dominated by ionic polarizability and ρrel. The Q × f values were considerably larger at BaM4Si5O17 (M = Yb and Y) ceramics with the high Utotal and low intrinsic dielectric loss. The τf values were controlled by the MO6 octahedron distortion and -VBa. The flexural strength was mainly dominated by pores and average grain size and reached the maximum value (156 MPa) at BaY4Si5O17 ceramic with small average gain sizes and high relative density. Additionally, a patch antenna was fabricated using high-performance BaY4Si5O17 ceramic characterized by a εr value of 9.02, a Q × f value of 60620 at 12.30 GHz, and a τf value of -37.65 ppm/°C. This design achieved a high simulated radiation efficiency of 82.70% and a gain of 5.60 dBi at 6.97 GHz. indicating potential applications of BaY4Si5O17 ceramic because of its low dielectric loss and high flexural strength.

Biomass-based controllable morphology of carbon microspheres with multi-layer hollow structure for superior performance in supercapacitors.

The electrochemical properties of corn starch (CS)-based hydrothermal carbon microsphere (CMS) electrode materials for supercapacitor are closely related to their structures. Herein, cetyltrimethyl ammonium bromide (CTAB) was used as a soft template to form the corn starch (CS)-based carbon microspheres with radial hollow structure in the inner and middle layers by hydrothermal and sol-gel method. Due to the introduction of multi-layer hollow structure of carbon microsphere, more micropores were produced during CO2 activation, which increased the specific surface area and improved the capacitance performance. Compared to commercial activated carbon, the four different morphologies of corn starch CMS had better electrochemical performances. Consequently, the proposed CO2-(CTAB)-CS-CS exhibits a high discharge specific capacitance of 242.5F/g at 1 A/g in three-electrode system with 6 M KOH electrolyte, better than commercial activated carbon with 208.5F/g. Moreover, excellent stability is achieved for CO2-(CTAB)-CS-CS with approximately 97.14 % retention of the initial specific capacitance value after 10,000 cycles at a current density of 2 A/g, while the commercial activated carbon has 86.96 % retention. This implies that the corn starch-based multilayer hollow CMS could be a promising electrode material for high-performance supercapacitors.

Heat exposure promotes sarcopenia via gut microbiota-derived metabolites.

The unprecedented rise in global ambient temperatures in the last decade has significantly impacted human health, yet how heat exposure affects the development of sarcopenia remains enigmatic. Here, we demonstrate that chronic heat exposure induces skeletal muscle volume loss, leading to muscle strength and functional decline in mice. The microbiota composition of heat-exposed mice was analyzed using 16S ribosomal DNA analysis. Liquid chromatography-mass spectrometry (LC-MS) was used to explore the effects of heat exposure on the blood metabolome and to further analyze the correlation between blood metabolism and gut microbiota. Transplantation of microbiota from heat-exposed mice to germ-free mice was sufficient to increase adverse effects on skeletal muscle function in the host. Mechanistically, using an untargeted metabolomics strategy, we reveal that altered gut microbiota due to high temperatures is associated with elevated serum levels of homocitrulline. Homocitrulline causes mitochondrial dysfunction in myocytes by exacerbating ferroptosis levels. And Nrf2 activator (Oltipraz) supplementation alleviates muscle atrophy and dysfunction induced by heat exposure. Our findings reveal the detrimental effects of heat exposure on muscle function and provide new strategies for treating sarcopenia.

Alterations of Myocardial Mitochondrial Morphology and Function in a Canine Model of Premature Ventricular Contractions-Induced Cardiomyopathy.

AIMS: Changes in myocardial mitochondrial morphology and function in premature ventricular contractions (PVCs)-induced cardiomyopathy (PVCCM) remain poorly studied. Here, we investigated the effects of PVCs with different coupling intervals (CIs) on myocardial mitochondrial remodelling in a canine model of PVCCM. METHODS AND RESULTS: Twenty-one beagles underwent pacemaker implantation and were randomised into the sham (n = 7), short-coupled PVCs (SCP, n = 7), and long-coupled PVCs (LCP, n = 7) groups. Right ventricular (RV) apical bigeminy was produced for 12-week to induce PVCCM in the SCP (CI, 250 ms) and LCP (CI, 350 ms) groups. Echocardiography was performed at baseline and biweekly thereafter to evaluate cardiac function. Masson's trichrome staining measured ventricular interstitial fibrosis. The ultrastructural morphology of the myocardial mitochondria was analysed using transmission electron microscopy. Mitochondrial Ca2+ concentration, reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) content, membrane potential, and electron transport chain (ETC) complex activity were measured to assess myocardial mitochondrial function. Twelve-week-PVCs led to left ventricular (LV) enlargement with systolic dysfunction, disrupted mitochondrial morphology, increased mitochondrial Ca2+ concentration and ROS levels, decreased mitochondrial ATP content and membrane potential, and impaired ETC complex activity in both the SCP and LCP groups (all p < 0.01 vs the sham group). Ventricular fibrosis was observed only in canines with LCP. Worse cardiac function and more pronounced abnormalities in mitochondrial morphology and function were observed in the LCP group than to the SCP group (all p < 0.05). CONCLUSION: We demonstrated myocardial mitochondrial abnormalities in dogs with PVCCM, characterised by abnormal mitochondrial morphology, mitochondrial Ca2+ overload, oxidative stress, and impaired mitochondrial energy metabolism. Compared to SCP, long-term LCP exposure resulted in more severe mitochondrial remodelling and cardiac dysfunction in dogs.

Enhancing Optoelectronic Anisotropy in Highly Oriented Thin Films by Fluorine Substitution in Novel Semiconducting Polymers.

The recent past has witnessed remarkable progress in organic electronics, driven by the quest for flexible, lightweight, and cost-effective electronic devices. Semiconducting polymers (SCPs) have emerged as key materials in this field, offering unique electronic and optoelectronic properties along with mechanical flexibility. This study focuses on designing, synthesizing, and utilizing novel donor-acceptor (D-A) copolymer-based SCPs introducing a difluorothiophene moiety in the polymeric backbone. The importance of fluorine substitution for backbone planarity was verified by density functional theory calculations, comparing it with a nonfluorine substituted counterpart. Through the Unidirectional Floating Film Transfer Method (UFTM), we fabricated highly oriented thin films, resulting in increased optical anisotropy with dichroic ratios reaching 19.3 in PC20-FT thin films, one of the highest optical anisotropy observed for solution processable SCP thin films. X-ray diffraction and atomic force microscopy results validated the increase in the crystallinity and domain size with the increasing alkyl chain length. Finally, we elucidate these findings in the context of electrical applications by fabricating organic field-effect transistors revealing anisotropic charge transport achieving a promising mobility of 1.24 cm2V-1s-1 and mobility anisotropy of 39.5. This study offers insights into the design principles and performance optimization of SCP-based devices, paving the way for advancements in plastic electronics.

Gastrointestinal Fistulas in Necrotizing Pancreatitis Receiving a Step-Up Approach Incidence, Risk Factors, Outcomes and Treatment.

Purpose: Necrotizing pancreatitis (NP) complicated by gastrointestinal fistula is challenging and understudied. As the treatment of necrotizing pancreatitis changed to a step-up strategy, we attempted to evaluate the incidence, risk factors, clinical outcomes and treatment of gastrointestinal fistulas in patients receiving a step-up approach. Methods: Clinical data from 1274 patients with NP from 2014-2022 were retrospectively analyzed. Multivariable logistic regression analysis was conducted to identify risk factors and propensity score matching (PSM) to explore clinical outcomes in patients with gastrointestinal fistulas. Results: Gastrointestinal fistulas occurred in 8.01% (102/1274) of patients. Of these, 10 were gastric fistulas, 52 were duodenal fistulas, 14 were jejunal or ileal fistulas and 41 were colonic fistulas. Low albumin on admission (OR, 0.936), higher CTSI (OR, 1.143) and invasive intervention prior to diagnosis of gastrointestinal fistula (OR, 5.84) were independent risk factors for the occurrence of gastrointestinal fistula, and early enteral nutrition (OR, 0.191) was a protective factor. Patients who developed a gastrointestinal fistula were in a worse condition on admission and had a poorer clinical outcome (p<0.05). After PSM, both groups of patients had similar baseline information and clinical characteristics at admission. The development of gastrointestinal fistulas resulted in new-onset persistent organ failure, increased open surgery, prolonged parenteral nutrition and hospitalization, but not increased mortality. The majority of patients received only conservative treatment and minimally invasive interventions, with 7 patients (11.3%) receiving surgery for upper gastrointestinal fistulas and 11 patients (26.9%) for colonic fistulas. Conclusion: Gastrointestinal fistulas occurred in 8.01% of NP patients. Independent risk factors were low albumin, high CTSI and early intervention, while early enteral nutrition was a protective factor. After PSM, gastrointestinal fistulas resulted in an increased proportion of NP patients receiving open surgery and prolonged hospitalization. The majority of patients with gastrointestinal fistulas treated with step-up therapy could avoid surgery.

Investigation of Polymer-Assisted CO2 Flooding to Enhance Oil Recovery in Low-Permeability Reservoirs.

CO2 flooding is a favorable technical means for the efficient development of low-permeability reservoirs, and it can also contribute to the realization of net-zero CO2 emissions. However, due to the unfavorable viscosity ratio and gravity overriding effect, CO2 channeling will inevitably occur, seriously affecting its storage and displacement effects. This paper conducts a systematic study on the application of polymer-assisted CO2 flooding in low-permeability reservoirs. Firstly, the polymer agent suitable for low-permeability reservoirs is optimized through the viscosity-increasing, rheological, and temperature- and salt-resistant properties of the solution. Then, the injectivity performance, resistance-increasing ability, and profile-improving effect of the polymer solution were evaluated through core experiments, and the optimum concentration was optimized. Finally, the enhanced oil recovery (EOR) effects of polymer-assisted and water-assisted CO2 flooding were compared. The results show that the temperature-resistant polymer surfactant (TRPS) has a certain viscosity-increasing performance, good temperature resistance performance, and can react with CO2 to increase the solution viscosity significantly. Meanwhile, TRPS has good injection performance and resistance-increasing effect. The resistance increasing factor (η and η') of TRPS-assisted CO2 flooding increases with increased permeability, the concentration of TRPS solution, and injection rounds. Considering η' and the profile improvement effect comprehensively, the application concentration of TRPS should be 1000 mg/L. The EOR effect of TRPS-assisted CO2 flooding is 8.21% higher than that of water-assisted CO2 flooding. The main effective period is in the first and second rounds, and the best injection round is three. The research content of this paper can provide data support for the field application of polymer-assisted CO2 flooding in low-permeability reservoirs.

Timing of minimally invasive step-up intervention for symptomatic pancreatic necrotic fluid collections: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Minimally invasive step-up interventions are now the standard treatment recommended by current guidelines for symptomatic pancreatic necrotic fluid collections (PNFC); however, it is controversial whether delayed treatment after four weeks should always be used in patients who have failed conservative treatment and whose condition has not improved or worsened. The aim of this meta-analysis was to evaluate the impacts of the different timing of interventions on the clinical outcomes and prognosis of patients with symptomatic PNEC requiring intervention. METHODS: We searched Embase, Cochrane Library, PubMed and Web of Science databases to identify comparative studies assessing the safety and efficacy of early and postponed interventions in treating symptomatic PNFC. PRIMARY OUTCOME: Mortality. Secondary outcomes included some major complications, need for further minimally invasive necrosectomy and length of hospital stay. RESULTS: This meta-analysis included ten studies (2 RCTs and 8 observational studies) with a total of 1178 symptomatic PNFC patients who required intervention. Pooled results showed that there was no significant difference between early minimally invasive intervention and postponed intervention in mortality(OR 1.41, 95%CI 0.93-2.12;p = 0.10) and the incidence of early and late complications, but the early intervention group had a significantly increased need for further minimally invasive necrosectomy compared with postponed intervention (OR 2.04,95%CI 1.04-4.03; p = 0.04). There was no increase in length of stay for patients who received early intervention compared to postponed drainage (MD 3.53, 95% CI -4.20, 11.27; p = 0.37). CONCLUSION: Intervention before four weeks should be considered for patients with PNFC complicated by persistent organ failure or infections, who have been treated conservatively to the maximum extent possible.

Carnosic acid protects against doxorubicin-induced cardiotoxicity through enhancing the Nrf2/HO-1 pathway.

Doxorubicin (DOX) is used extensively in anticancer therapy, but its clinical application is limited due to its cardiotoxicity. Carnosic acid (CA) is a bioactive compound found in rosemary. It has been shown to reduce inflammation and reactive oxygen species. The purpose of this study was to investigate the potential cardioprotective effects of CA in response to DOX-induced cardiotoxicity. Here, C57BL/6 mice were administered an intraperitoneal injection of DOX (5 mg kg-1, ip) once a week for three consecutive weeks and treated with CA (40 mg kg-1, ig) for a three-week experimental period. For in vitro study, neonatal rat ventricular cardiomyocytes were used to validate the protective effects of CA (20 µM) in response to DOX-induced cardiotoxicity. CA markedly suppressed oxidative stress, apoptosis, and pyroptosis responses in the mouse hearts, eventually improving cardiac function. CA showed its antioxidant effect by activating nuclear factor erythroid 2-related factor (Nrf2) and its downstream heme oxygenase-1 (HO-1); CA also reduced oxidative stress by lowering the MDA and lipid ROS levels and raising the SOD and GSH-px levels. Additionally, CA treatment significantly increased Bcl-2 and inhibited Bax and Caspase-3 cleavage in DOX-induced cardiotoxicity. Moreover, CA suppressed the NOD-like receptor protein 3 (NLRP3) pathway to mitigate pyroptosis, as evidenced by lowered caspase1, interleukin-18, and interleukin-1ß. Consistently, the transfection of Nrf2-siRNA eliminated the protective effects of CA on cardiomyocytes. Altogether, our findings demonstrated that CA inhibited NLRP3 inflammasomes via activating the Nrf2-related cytoprotective system and protected the heart from oxidative damage, apoptosis, and pyroptosis, implying that the use of CA could be a potential therapeutic strategy in the prevention of DOX-associated myocardiopathy.

Serinc2 deficiency exacerbates sepsis-induced cardiomyopathy by enhancing necroptosis and apoptosis.

In critical care medicine, sepsis is a potentially fatal syndrome characterized by multi-organ dysfunction and eventual failure. Sepsis-induced cardiomyopathy (SIC) is characterized by decreased venstricular contractility. Serine incorporator 2 (Serinc2) is a protein involved in phosphatidylserine biosynthesis and membrane incorporation. It may also be a protective factor in septic lung injury. However, it is unknown whether Serinc2 influences SIC onset or progression. In the present study, we found that Serinc2 was downregulated in the cardiomyocytes of cecal ligation and puncture (CLP)-induced SIC and in neonatal rat cardiomyocytes (NRCMs) exposed to lipopolysaccharides (LPS). Serinc2 knockout (KO) exacerbated sepsis-induced myocardial inflammation, necroptosis, apoptosis, myocardial damage, and contractility impairment. Furthermore, the lack of Serinc2 in cardiomyocytes aggravated LPS-induced cardiomyopathic inflammation, necroptosis, and apoptosis. An adenovirus overexpressing Serinc2 inhibited the inflammatory response and favored cardiomyocyte survival. A mechanistic analysis revealed that Serinc2 deficiency exacerbated LPS-induced cardiac dysfunction by inhibiting the protein kinase B (Akt)/glycogen synthase kinase 3 beta (GSK-3ß) signaling pathway that regulates necrotic complex formation and apoptotic pathways in cardiomyopathy. The findings of the present work demonstrated that Serinc2 plays an essential role in SIC and is, therefore, promising as a prophylactic and therapeutic target for this condition.

lncRNA Hnscr Regulates Lipid Metabolism by Mediating Adipocyte Lipolysis.

Obesity is a process of fat accumulation due to the imbalance between energy intake and consumption. Long noncoding RNA (lncRNA) Hnscr is crucial for metabolic regulation, but its roles in lipid metabolism during obesity are still unknown. In this article, we found that the expression of Hnscr gradually decreased in adipose tissues of diet-induced obese mice. Furthermore, the deletion of Hnscr promoted an increase in body weight and adipose tissue weight by upregulating the expression of lipogenesis genes and downregulating lipolysis genes in inguinal white adipose tissue (iWAT) and brown adipose tissue. In vitro knockdown of Hnscr in adipocytes resulted in reduced lipolysis of adipocytes. Overexpression of Hnscr by adenovirus or drug mimics showed the opposite. Mechanistically, Hnscr regulated adipose lipid metabolism by mediating the cyclic adenosine monophosphate/protein kinase A signaling pathway. This study identifies the initial characterization of Hnscr as a critical modifier that regulates lipid metabolism, suggesting that lncRNA Hnscr is a potential target for treating obesity.