Simultaneous aerobic nitrogen and phosphorus removal by novel halotolerant fungus Mucor circinelloides SNDM1: Function and metabolism pathway.

Fungi capable of simultaneous nitrogen and phosphorus removal from wastewater is rarely found. Here, a novel fungal strain (SNDM1) performing heterotrophic nitrification, aerobic denitrification, and phosphate removal was isolated and identified as Mucor circinelloides. The favorable nutrient removal conditions by the strain using glucose were C/N ratios of 25-30, salinities of 0 %-3 %, and pH of 7.5. Strain SNDM1 achieved ammonium, nitrite, nitrate, and phosphate removal rates of 5.23, 10.08, 4.88, and 0.97 mg/L/h. Nitrogen balance indicated that gaseous (18.60 %-24.55 %) and intracellular nitrogen (43.76 %-70.63 %) were primary fate of initial nitrogen. Enzyme activity revealed that ammonium removal occurred through heterotrophic nitrification and aerobic denitrification. Removed phosphorus was mainly transformed into cell membranes (56 %-64 %) and extracellular polymeric substances (20 %-26 %). Orthophosphate was the major intracellular phosphorus species, while polyphosphate and pyrophosphate existed extracellularly. These findings highlight the potential of this fungal strain for bioremediating polluted wastewater.

Monocyte/macrophage-mediated venous thrombus resolution.

Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.

Comparative study of the clinical value of digital subtraction angiography via femoral and radial arterial paths.

OBJECTIVE: To evaluate the clinical efficacy of digital subtraction angiography (DSA) performed via femoral artery and radial artery approaches. METHODS: This retrospective study included 480 patients requiring cerebral vascular angiography at the First People's Hospital of Changde City from March 2020 to February 2022. Patients were divided into the femoral artery group (transfemoral approach, n=400) and the radial artery group (transradial approach, n=80) according to the surgical route. We compared perioperative metrics, success rates of selective angiography and puncture, and complication rates (including pseudoaneurysm, urinary retention, hematoma, vasospasm) between the groups. Multivariate logistic regression was used to analyze factors influencing the failure of angiography by each approach. RESULTS: The radial artery group exhibited shorter durations for puncture, hemostasis, exposure, operation, and postoperative recovery (all P<0.001). The success rate of selective angiography was higher in the radial artery group (93.75%) compared to the femoral artery group (85.25%) (χ2=4.168, P=0.041). No significant difference was found in puncture success rates between the groups (χ2=0.235, P=0.628). The overall complication rate was significantly lower in the radial artery group (2.50%) compared to the femoral artery group (9.25%) (χ2=4.069, P=0.044). Gender and low-density lipoprotein cholesterol levels were significant predictors of angiography failure in both approaches (both P<0.05). CONCLUSION: The transradial approach for DSA is safe and feasible, offering advantages in terms of operational time and complication rates, making it the preferred method in clinical settings.

Electrolyte Composition-Dependent Product Selectivity in CO2 Reduction with a Porphyrinic Metal-Organic Framework Catalyst.

A copper porphyrin-derived metal-organic framework electrocatalyst, FICN-8, was synthesized and its catalytic activity for CO2 reduction reaction (CO2RR) was investigated. FICN-8 selectively catalyzed electrochemical reduction of CO2 to CO in anhydrous acetonitrile electrolyte. However, formic acid became the dominant CO2RR product with the addition of a proton source to the system. Mechanistic studies revealed the change of major reduction pathway upon proton source addition, while catalyst-bound hydride (*H) species was proposed as the key intermediate for formic acid production. This work highlights the importance of electrolyte composition on CO2RR product selectivity.

The chemokine CCL14 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma.

BACKGROUND: Chemokine ligand 14, which has a C-C motif (CCL14), mediates the immunological milieu around tumors. However, its role in the progression of lung adenocarcinoma (LUAD) is still unknown. Our objectives were to study the association between CCL14 and tumor-infiltrating immune cells (TIICs) as well as the predictive significance of CCL14 in LUAD. METHODS: The expression of CCL14 in LUAD was examined by using the Oncomine, The Cancer Genome Atlas (TCGA), The University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), and Human Protein Atlas databases. To determine the prognostic significance of CCL14 in LUAD, researchers used the Kaplan‒Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA, version 2). We utilized TIMER and GEPIA2 to investigate the connection between CCL14 and TIICs. Gene set enrichment analysis (GSEA) was used to test for functional enrichment of genes. We used RT‒qPCR to measure CCL14 expression and Cell Counting Kit-8, Transwell, and wound healing assays to investigate the biological role of CCL14. RESULTS: The prognosis of patients with LUAD was worse when CCL14 expression was low. Statistical analysis revealed that CCL14 mRNA expression was significantly greater in lung epithelial cells than in LUAD cell lines in vitro. Enhancing CCL14 expression reduced cell migration, invasion, and proliferation. The results of the immune infiltration research showed that CCL14 and TIICs were positively correlated. Different immune infiltration patterns associated with CCL14 were also shown by TIIC markers. According to GSEA, histone deacetylases, G2/M checkpoints, and Notch signaling pathways were associated with low CCL14 expression. CONCLUSIONS: CCL14 is anticipated to emerge as a prognostic marker and therapeutic target for LUAD due to its role in regulating TIICs, suggesting that it may be an antioncogene.

FXR activation remodels hepatic and intestinal transcriptional landscapes in metabolic dysfunction-associated steatohepatitis.

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

Activity-based protein profiling in drug/pesticide discovery: Recent advances in target identification of antibacterial compounds.

Given the escalating incidence of bacterial diseases and the challenge posed by pathogenic bacterial resistance, it is imperative to identify appropriate methodologies for conducting proteomic investigations on bacteria, and thereby promoting the target-based drug/pesticide discovery. Interestingly, a novel technology termed "activity-based protein profiling" (ABPP) has been developed to identify the target proteins of active molecules. However, few studies have summarized advancements in ABPP for identifying the target proteins in antibacterial-active compounds. In order to accelerate the discovery and development of new drug/agrochemical discovery, we provide a concise overview of ABPP and its recent applications in antibacterial agent discovery. Diversiform cases were cited to demonstrate the potential of ABPP for target identification though highlighting the design strategies and summarizing the reported target protein of antibacterial compounds. Overall, this review is an excellent reference for probe design towards antibacterial compounds, and offers a new perspective of ABPP in bactericide development.

Application of natural-products repurposing strategy to discover novel FtsZ inhibitors: Bactericidal evaluation and the structure-activity relationship of sanguinarine and its analogs.

The novel bactericidal target-filamentous temperature-sensitive protein Z (FtsZ)-has drawn the attention of pharmacologists to address the emerging issues with drug/pesticide resistance caused by pathogenic bacteria. To enrich the structural diversity of FtsZ inhibitors, the antibacterial activity and structure-activity relationship (SAR) of natural sanguinarine and its analogs were investigated by using natural-products repurposing strategy. Notably, sanguinarine and chelerythrine exerted potent anti-Xanthomonas oryzae pv. oryzae (Xoo) activity, with EC50 values of 0.96 and 0.93 mg L-1, respectively, among these molecules. Furthermore, these two compounds could inhibit the GTPase activity of XooFtsZ, with IC50 values of 241.49 µM and 283.14 µM, respectively. An array of bioassays including transmission electron microscopy (TEM), fluorescence titration, and Fourier transform infrared spectroscopy (FT-IR) co-verified that sanguinarine and chelerythrine were potential XooFtsZ inhibitors that could interfere with the assembly of FtsZ filaments by inhibiting the GTPase hydrolytic ability of XooFtsZ protein. Additionally, the pot experiment suggested that chelerythrine and sanguinarine demonstrated excellent curative activity with values of 59.52% and 54.76%, respectively. Excitedly, these two natural compounds also showed outstanding druggability, validated by acceptable drug-like properties and low toxicity on rice. Overall, the results suggested that chelerythrine was a new and potential XooFtsZ inhibitor to develop new bactericide and provided important guiding values for rational drug design of FtsZ inhibitors. Notably, our findings provide a novel strategy to discover novel, promising and green bacterial compounds for the management of plant bacterial diseases.

Research Progress of Biosensor Based on Organic Photoelectrochemical Transistor.

In order to solve the food safety problem better, it is very important to develop a rapid and sensitive technology for detecting food contamination residues. Organic photoelectrochemical transistor (OPECT) biosensor rely on the photovoltage generated by a semiconductor upon excitation by light to regulate the conductivity of the polymer channels and realize biosensor analysis under zero gate bias. This technology integrates the excellent characteristics of photoelectrochemical (PEC) bioanalysis and the high sensitivity and inherent amplification ability of organic electrochemical transistor (OECT). Based on this, OPECT biosensor detection has been proven to be superior to traditional biosensor detection methods. In this review, we summarize the research status of OPECT biosensor in disease markers and food residue analysis, the basic principle, classification, and biosensing mechanism of OPECT biosensor analysis are briefly introduced, and the recent applications of biosensor analysis are discussed according to the signal strategy. We mainly introduced the OPECT biosensor analysis methods applied in different fields, including the detection of disease markers and food hazard residues such as prostate-specific antigen, heart-type fatty acid binding protein, T-2 toxin detection in milk samples, fat mass and objectivity related protein, ciprofloxacin in milk. The OPECT biosensor provides considerable development potential for the construction of safety analysis and detection platforms in many fields, such as agriculture and food, and hopes to provide some reference for the future development of biosensing analysis methods with higher selectivity, faster analysis speed and higher sensitivity.

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia.

BACKGROUND: Patients with chronic heart failure (CHF) frequently develop hyperuricemia, an elevated serum uric acid level, associated with adverse outcomes. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction (HFrEF), irrespective of diabetes. However, dapagliflozin's effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear. AIM: To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 200 patients with CHF and hyperuricemia, with HFrEF and serum uric acid levels ≥ 7 mg/dL (≥ 416 µmol/L). The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months. The primary endpoint was the change in serum uric acid level from baseline to 24 months. Secondary endpoints included changes in left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QoL) scores, as well as the incidence of cardiovascular death and hospitalization for heart failure. RESULTS: At 24 months, dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL (71 µmol/L) compared with placebo (95%CI: -1.5 to -0.9; P < 0.001). Dapagliflozin also significantly improved LVEF by 3.5% (95%CI: 2.1-4.9; P < 0.001), NT-proBNP by 25% (95%CI: 18-32; P < 0.001), and QoL scores by 10 points (95%CI: 7-13; P < 0.001) and reduced the risk of cardiovascular death and hospitalization for heart failure by 35% (95%CI: 15-50; P = 0.002) compared with the placebo. Adverse events were similar between the two groups, except for a higher rate of genital infections in the dapagliflozin group (10% vs 2%, P = 0.01). CONCLUSION: Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia. Therefore, dapagliflozin may be a useful therapeutic option for this high-risk population.

Breaking the barrier: Nanoparticle-enhanced radiotherapy as the new vanguard in brain tumor treatment.

The pursuit of effective treatments for brain tumors has increasingly focused on the promising area of nanoparticle-enhanced radiotherapy (NERT). This review elucidates the context and significance of NERT, with a particular emphasis on its application in brain tumor therapy-a field where traditional treatments often encounter obstacles due to the blood-brain barrier (BBB) and tumor cells' inherent resistance. The aims of this review include synthesizing recent advancements, analyzing action mechanisms, and assessing the clinical potential and challenges associated with nanoparticle (NP) use in radiotherapy enhancement. Preliminary preclinical studies have established a foundation for NERT, demonstrating that nanoparticles (NPs) can serve as radiosensitizers, thereby intensifying radiotherapy's efficacy. Investigations into various NP types, such as metallic, magnetic, and polymeric, have each unveiled distinct interactions with ionizing radiation, leading to an augmented destruction of tumor cells. These interactions, encompassing physical dose enhancement and biological and chemical radio sensitization, are crucial to the NERT strategy. Although clinical studies are in their early phases, initial trials have shown promising results in terms of tumor response rates and survival, albeit with mindful consideration of toxicity profiles. This review examines pivotal studies affirming NERT's efficacy and safety. NPs have the potential to revolutionize radiotherapy by overcoming challenges in targeted delivery, reducing off-target effects, and harmonizing with other modalities. Future directions include refining NP formulations, personalizing therapies, and navigating regulatory pathways. NERT holds promise to transform brain tumor treatment and provide hope for patients.

ASS1 Enhances Anoikis Resistance via AMPK/CPT1A-mediated Fatty Acid Metabolism in Ovarian Cancer.

Metastasis is the leading cause of death in ovarian cancer (OC), with anoikis resistance being a crucial step for detached OC cells survival. Despite extensive research, targeting anoikis resistance remians a challenge. Here, we identify argininosuccinate synthase 1 (ASS1), a key enzyme in urea cycle, is markedly upregulated in OC cells in detached culture and is associated with increased anoikis resistance and metastasis. Disruption of the AMP/ATP balance by elevated ASS1 activates AMPK and its downstream factor, CPT1A. Then, ASS1 enhances FAO, leading to higher ATP generation and lipid utilization. Inhibition of CPT1A reverses ASS1-induced FAO. Our study gives some new functional insights into OC metabolism and represents a shift from traditional views, expanding ASS1's relevance beyond nitrogen metabolism to fatty acid metabolism. It uncovers how ASS1-induced FAO disrupts the AMP/ATP balance, leading to AMPK activation. By identifying the ASS1/AMPK/CPT1A axis as crucial for OC anoikis resistance and metastasis, our study opens up new avenues for therapeutic interventions.

WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a common complication of acute and severe neurosurgery. Remodeling of N6-methyladenosine (m6A) stabilization may be an attractive treatment option for neurological dysfunction after TBI. In the present study, we explored the epigenetic methylation of RNA-mediated NLRP3 inflammasome activation after TBI. METHODS: Neurological dysfunction, histopathology, and associated molecules were examined in conditional knockout (CKO) WTAP[flox/flox, Camk2a-cre], WTAPflox/flox, and pAAV-U6-shRNA-YTHDF1-transfected mice. Primary neurons were used in vitro to further explore the molecular mechanisms of action of WTAP/YTHDF1 following neural damage. RESULTS: We found that WTAP and m6A levels were upregulated at an early stage after TBI, and conditional deletion of WTAP in neurons did not affect neurological function but promoted functional recovery after TBI. Conditional deletion of WTAP in neurons suppressed neuroinflammation at the TBI early phase: WTAP could directly act on NLRP3 mRNA, regulate NLRP3 mRNA m6A level, and promote NLRP3 expression after neuronal injury. Further investigation found that YTH domain of YTHDF1 could directly bind to NLRP3 mRNA and regulate NLRP3 protein expression. YTHDF1 mutation or silencing improved neuronal injury, inhibited Caspase-1 activation, and decreased IL-1ß levels. This effect was mediated via suppression of NLRP3 protein translation, which also reversed the stimulative effect of WTAP overexpression on NLRP3 expression and inflammation. CONCLUSION: Our results indicate that WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after TBI and that WTAP/m6A/YTHDF1 downregulation therapeutics is a viable and promising approach for preserving neuronal function after TBI, which can provide support for targeted drug development.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury.

Objective: To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators. Method: The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results: 73 patients were enrolled. Age among five groups was statistically different ( P = 0.032). Alanine aminotransferase (ALT) ( P = 0.033) and aspartate aminotransferase (AST) ( P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT ( r = 0.697, P = 0.025), AST ( r = 0.721, P = 0.019), and IL-6 in NSAIDs group. Conclusion: Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI.

Comparison of the chemical constituents of Saposhnikoviae Radix associated with three different growth patterns and its therapeutic effect against atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Saposhnikoviae Radix (SR) was initially documented in Shennong Bencao Jing classics for its properties in dispelling wind, dissolving surface, relieving pain, and alleviating spasms. This herb is commonly used in traditional Chinese medicine to address conditions that affect the body's surface, by aiding in the expulsion of pathogens from the surface and alleviating pain associated with the immune response. Atopic dermatitis (AD) is a prevalent allergic skin disorder, and the therapeutic effects of SR in dispelling wind and relieving the body's surface are consistent with the clinical symptoms commonly observed in AD. AIM OF THE STUDY: The anti-AD effects of SR were examined under three different growth patterns to identify active pharmacodynamic compounds. The results provide insight into the clinical efficacy of wild and cultivated SR. MATERIALS AND METHODS: The efficacy of wild, wild-simulated, and cultivated SR was assessed in a mouse model of AD. In addition, the effects of wild and varying doses of cultivated SR were evaluated in mice with short-term AD symptoms. GC-MS and UPLC-MS/MS were used to analyze the chemical components of the three SR treatments and molecular docking was used to identify active components. RESULTS: A mouse model of AD was used to assess the pharmacodynamic effects of SR prepared by three different cultivation methods. The study found that all three SR preparations improved phenotypic markers and histopathological features in the AD mouse model. The efficacy of wild SR and wild-simulated SR was similar, although there was a significant difference between wild and cultivated SR. Both wild SR and various doses of cultivated SR ameliorated skin injuries and reduced inflammation in serum and skin tissues. Furthermore, skin thickness, inflammatory cells, mast cell infiltration, and IL-33 expression improved following treatment. Notably, wild SR, double-cultivated SR, and triple-cultivated SR demonstrated significant therapeutic effects. An analysis using GC-MS revealed the presence of 55, 52, and 43 volatile oils in the three SR preparations, with more common components observed between wild and wild-simulated SR. Fewer common components were evident between cultivated and wild SR. UPLC-MS/MS analysis identified a total of 37 compounds, with larger relative peak areas observed for the chromogenic ketones. Molecular docking studies revealed that certain compounds, such as n-propyl 9,12-octadecadienoate, (E)-9-octadecenoic acid ethyl ester, and various chromogenic ketones, such as cimifugin, 5-O-methyIvisamminol, hamaudol, 3'-O-acetylhamaudol, 3'-O-angeloyhamandol, adenosine and farnesylaceton, may be the major substances that distinguish the activities of SR with three different growth patterns. CONCLUSION: Variations in the anti-AD efficacy of SR with three growth patterns were identified, and their chemical composition differences were determined. These findings suggest that increasing the dosage of cultivated SR could potentially be a viable clinical alternative for atopic dermatitis treatment.

The Inflammation-Fibrosis Combined Index: A Novel Marker for Predicting Left Ventricular Reverse Remodeling and Prognosis in Patients with HFrEF.

Background: Inflammation and cardiac fibrosis are important pathogenic drivers of heart failure. The fibrosis-4 index (FIB-4) is associated with a higher degree of fibrosis. The systemic immune inflammation index (SII) is associated with a higher degree of systemic inflammation status. Previous studies have shown that they are associated with a poor prognosis for cardiovascular disease. We sought to investigate the value of FIB-4 combined with the SII as a novel inflammation-fibrosis combined index (IFCI) in predicting left ventricular reverse remodeling (LVRR) and prognosis among reduced ejection fraction heart failure (HFrEF) patients. Methods: A total of 895 patients with HFrEF were continuously recruited. Receiver operating characteristic curves were drawn to assess the abilities of inflammation-fibrosis indicators to predict LVRR. Multivariable Cox regression analysis was used to examine independent predictors of composite cardiac events and all-cause death. Results: After six months of follow-up, 344 (38.4%) patients experienced LVRR. The IFCI had the largest area under the curve (0.835, P < 0.001). In multivariate-adjusted logistic regression analyses, FIB-4, SII, and IFCI were predictive of LVRR (P value < 0.05). The IFCI was associated with a 3.686-fold higher risk of non-LVRR (odds ratio [OR] = 3.686, P < 0.001). Moreover, an increased IFCI predicted a poor prognosis in HFrEF patients. The highest risk of composite cardiac events (hazard ratio [HR] = 2.716, P < 0.001) was observed in the top IFCI-tertile group, and similar results were found regarding independent risk indicators of all-cause death. Conclusion: In summary, this study indicated that increased IFCI at admission offers good predictability regarding non-LVRR and predicts the risk of all-cause mortality or composite cardiovascular events due to HFrEF patients and could be used as a novel marker.

A critical role for the nuclear protein Akirin in larval development in Henosepilachna vigintioctopunctata.

Akirin is a nuclear protein that controls development in vertebrates and invertebrates. The function of Akirin has not been assessed in any Coleopteran insects. We found that high levels of akirin transcripts in Henosepilachna vigintioctopunctata, a serious Coleopteran potato defoliator (hereafter Hvakirin), were present at prepupal, pupal and adult stages, especially in larval foregut and fat body. RNA interference (RNAi) targeting Hvakirin impaired larval development. The Hvakirin RNAi larvae arrested development at the final larval instar stage. They remained as stunted larvae, gradually blackened and finally died. Moreover, the remodelling of gut and fat body was inhibited in the Hvakirin depleted larvae. Two layers of cuticles, old and newly formed, were noted in the dsegfp-injected animals. In contrast, only a layer of cuticle was found in the dsakirin-injected beetles, indicating the arrest of larval development. Furthermore, the expression of three transforming growth factor-ß cascade genes (Hvsmox, Hvmyo and Hvbabo), a 20-hydroxyecdysone (20E) receptor gene (HvEcR) and six 20E response genes (HvHR3, HvHR4, HvE75, HvBrC, HvE93 and Hvftz-f1) was significantly repressed, consistent with decreased 20E signalling. Conversely, the transcription of a juvenile hormone (JH) biosynthesis gene (Hvjhamt), a JH receptor gene (HvMet) and two JH response genes (HvKr-h1 and HvHairy) was greatly enhanced. Our findings suggest a critical role of Akirin in larval development in H. vigintioctopunctata.

Hepatitis B-related hepatocellular carcinoma: classification and prognostic model based on programmed cell death genes.

Instruction: Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Programmed cell death (PCD) is a critical process in suppressing tumor growth, and alterations in PCD-related genes may contribute to the progression of HBV-HCC. This study aims to develop a prognostic model that incorporates genomic and clinical information based on PCD-related genes, providing novel insights into the molecular heterogeneity of HBV-HCC through bioinformatics analysis and experimental validation. Methods: In this study, we analyzed 139 HBV-HCC samples from The Cancer Genome Atlas (TCGA) and validated them with 30 samples from the Gene Expression Omnibus (GEO) database. Various bioinformatics tools, including differential expression analysis, gene set variation analysis, and machine learning algorithms were used for comprehensive analysis of RNA sequencing data from HBV-HCC patients. Furthermore, among the PCD-related genes, we ultimately chose DLAT for further research on tissue chips and patient cohorts. Besides, immunohistochemistry, qRT-PCR and Western blot analysis were conducted. Results: The cluster analysis identified three distinct subgroups of HBV-HCC patients. Among them, Cluster 2 demonstrated significant activation in DNA replication-related pathways and tumor-related processes. Analysis of copy number variations (CNVs) of PCD-related genes also revealed distinct patterns in the three subgroups, which may be associated with differences in pathway activation and survival outcomes. DLAT in tumor tissues of HBV-HCC patients is upregulated. Discussion: Based on the PCD-related genes, we developed a prognostic model that incorporates genomic and clinical information and provided novel insights into the molecular heterogeneity of HBV-HCC. In our study, we emphasized the significance of PCD-related genes, particularly DLAT, which was examined in vitro to explore its potential clinical implications.

The association between vascular access satisfaction and all-cause mortality in maintenance hemodialysis patients.

BACKGROUND: The mortality is significantly higher in patients undergoing maintenance hemodialysis (MHD) than in the general population. It is well-known that vascular access (VA) is critical for MHD patients. But the association between VA satisfaction and all-cause mortality in MHD patients is still not clear. The aim of this study was to explore the relationship between VA satisfaction and all-cause mortality in MHD patients with a 30-month follow-up. METHODS: Two hundred twenty-nine MHD patients in two dialysis centers were enrolled in this observational prospective study. VA satisfaction was assessed using the Short Form Vascular Access Questionnaire (VAQ). Health-related quality of life (HRQoL) score was calculated with Short Form 36 (SF-36) questionnaire. Multiple logistic regression analysis was used to evaluate the influencing factors of all-cause mortality. RESULTS: During the 30-month follow-up period, 35 patients dropped out of the study. Among them, 31 patients died, and 4 patients stopped MHD treatment after renal transplantation. Multivariable analyses showed that the age, VAQ total score, social functioning score and dialysis-related complication score of the VAQ, the total score and MCS of the SF-36 were factors influencing all-cause mortality in MHD patients. The Kaplan-Meier curve further showed that the cumulative survival probability was significantly higher in the MHD patients with VAQ scores <7 at baseline than in patients with VAQ scores ⩾7 (p = 0.031). INCLUSION: The present study showed that VA satisfaction was significantly associated with all-cause mortality in MHD patients. These findings suggest that a holistic approach is required for VA choice.

Decreased connexin 40 expression of the sinoatrial node mediates ischemic stroke-induced arrhythmia in mice.

BACKGROUND: Arrhythmia is the most common cardiac complication after ischemic stroke. Connexin 40 is the staple component of gap junctions, which influences the propagation of cardiac electrical signals in the sinoatrial node. However, the role of connexin 40 in post-stroke arrhythmia remains unclear. METHODS: In this study, a permanent middle cerebral artery occlusion model was used to simulate the occurrence of an ischemic stroke. Subsequently, an electrocardiogram was utilized to record and assess variations in electrocardiogram measures. In addition, optical tissue clearing and whole-mount immunofluorescence staining were used to confirm the anatomical localization of the sinoatrial node, and the sinoatrial node tissue was collected for RNA sequencing to screen for potential pathological mechanisms. Lastly, the rAAV9-Gja5 virus was injected with ultrasound guidance into the heart to increase Cx40 expression in the sinoatrial node. RESULTS: We demonstrated that the mice suffering from a permanent middle cerebral artery occlusion displayed significant arrhythmia, including atrial fibrillation, premature ventricular contractions, atrioventricular block, and abnormal electrocardiogram parameters. Of note, we observed a decrease in connexin 40 expression within the sinoatrial node after the ischemic stroke via RNA sequencing and western blot. Furthermore, rAAV9-Gja5 treatment ameliorated the occurrence of arrhythmia following stroke. CONCLUSIONS: In conclusion, decreased connexin 40 expression in the sinoatrial node contributed to the ischemic stroke-induced cardiac arrhythmia. Therefore, enhancing connexin 40 expression holds promise as a potential therapeutic approach for ischemic stroke-induced arrhythmia.