Heat-Stress Impacts on Developing Bovine Oocytes: Unraveling Epigenetic Changes, Oxidative Stress, and Developmental Resilience.

Extreme temperature during summer may lead to heat stress in cattle and compromise their productivity. It also poses detrimental impacts on the developmental capacity of bovine budding oocytes, which halt their fertility. To mitigate the adverse effects of heat stress, it is necessary to investigate the mechanisms through which it affects the developmental capacity of oocytes. The primary goal of this study was to investigate the impact of heat stress on the epigenetic modifications in bovine oocytes and embryos, as well as on oocyte developmental capacity, reactive oxygen species, mitochondrial membrane potential, apoptosis, transzonal projections, and gene expression levels. Our results showed that heat stress significantly reduced the expression levels of the epigenetic modifications from histone H1, histone H2A, histone H2B, histone H4, DNA methylation, and DNA hydroxymethylation at all stages of the oocyte and embryo. Similarly, heat stress significantly reduced cleavage rate, blastocyst rate, oocyte mitochondrial-membrane potential level, adenosine-triphosphate (ATP) level, mitochondrial DNA copy number, and transzonal projection level. It was also found that heat stress affected mitochondrial distribution in oocytes and significantly increased reactive oxygen species, apoptosis levels and mitochondrial autophagy levels. Our findings suggest that heat stress significantly impacts the expression levels of genes related to oocyte developmental ability, the cytoskeleton, mitochondrial function, and epigenetic modification, lowering their competence during the summer season.

P53 upregulation by USP7-engaging molecular glues.

Molecular glues are typically small chemical molecules that act at the interface between a target protein and degradation machinery to trigger ternary complex formation. Identifying molecular glues is challenging. There is a scarcity of target-specific upregulating molecular glues, which are highly anticipated for numerous targets, including P53. P53 is degraded in proteasomes through polyubiquitination by specific E3 ligases, whereas deubiquitinases (DUBs) remove polyubiquitination conjugates to counteract these E3 ligases. Thus, small-molecular glues that enhance P53 anchoring to DUBs may stabilize P53 through deubiquitination. Here, using small-molecule microarray-based technology and unbiased screening, we identified three potential molecular glues that may tether P53 to the DUB, USP7, and elevate the P53 level. Among the molecular glues, bromocriptine (BC) is an FDA-approved drug with the most robust effects. BC was further verified to increase P53 stability via the predicted molecular glue mechanism engaging USP7. Consistent with P53 upregulation in cancer cells, BC was shown to inhibit the proliferation of cancer cells in vitro and suppress tumor growth in a xenograft model. In summary, we established a potential screening platform and identified potential molecular glues upregulating P53. Similar strategies could be applied to the identification of other types of molecular glues that may benefit drug discovery and chemical biology studies.

Oxidative phosphorylation regulates B cell effector cytokines and promotes inflammation in multiple sclerosis.

Dysregulated B cell cytokine production contributes to pathogenesis of immune-mediated diseases including multiple sclerosis (MS); however, the underlying mechanisms are poorly understood. In this study we investigated how cytokine secretion by pro-inflammatory (GM-CSF-expressing) and anti-inflammatory (IL-10-expressing) B cells is regulated. Pro-inflammatory human B cells required increased oxidative phosphorylation (OXPHOS) compared with anti-inflammatory B cells. OXPHOS reciprocally modulated pro- and anti-inflammatory B cell cytokines through regulation of adenosine triphosphate (ATP) signaling. Partial inhibition of OXPHOS or ATP-signaling including with BTK inhibition resulted in an anti-inflammatory B cell cytokine shift, reversed the B cell cytokine imbalance in patients with MS, and ameliorated neuroinflammation in a myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis mouse model. Our study identifies how pro- and anti-inflammatory cytokines are metabolically regulated in B cells and identifies ATP and its metabolites as a "fourth signal" that shapes B cell responses and is a potential target for restoring the B cell cytokine balance in autoimmune diseases.

Investigation of catalytic methane oxidation over Ag/Co2MOx (M = Co, Ni, Cu) catalysts with varying interfacial electron transfer.

Atom-doped Co3O4 catalysts loaded with Ag were examined as cost-effective catalysts for methane oxidation. The synthesized Ag/Co2NiOx catalysts exhibited distinctive surface characteristics in contrast with Ag/Co3O4 and Ag/Co2CuOx catalysts prepared using a similar method. Characterization results unveiled that Ag/Co2NiOx featured a higher presence of active surface oxygen species, lattice defects, a larger surface area, and enhanced reducibility. A methane oxidation catalytic performance followed the sequence: Ag/Co2NiOx > Ag/Co3O4 > Ag/Co2CuOx. The investigation delved into methane degradation pathways on the surfaces of three catalysts, examining their behavior under both aerobic and anaerobic atmospheres through in-situ DRIFTS analysis. Furthermore, introducing Ag showed a marked positive effect on Co-Ni mixed oxide, inducing electron transfer and a more active electron system, whereas it exhibited an inverse impact within the surface of Co-Cu mixed oxide. This work provides innovative perspectives on the development of forthcoming environmental catalysts.

In vivo evidence of sea buckthorn relieving oxidative stress and improving immune performance of common carp (Cyprinus carpio L.).

BACKGROUND: Sea buckthorn has the functions of antioxidation, antitumor, anti-inflammation and regulating energy metabolism. In order to investigate the effects of sea buckthorn powder and sea buckthorn flavonoids on the antioxidant properties, immune function and muscle fatty acid composition of common carp, an oral feeding experiment was carried out. RESULTS: The administration of glucose significantly reduced the levels of glutathione and the activity of total antioxidant capacity enzyme in serum and hepatopancreas, while concurrently upregulating the level of malondialdehyde (MDA)(P < 0.05). Conversely, oral intake of sea buckthorn powder and flavonoids increased antioxidant enzyme activity and decreased MDA levels. In terms of antioxidant molecular indicators, sea buckthorn powder and sea buckthorn flavonoids significantly increased the mRNA levels of nuclear factor NF-E2-related factor (nrf2) in the hepatopancreas and muscle. Meanwhile, mRNA expression levels of downstream antioxidant-related genes (gr, cat, gpx, and sod) regulated by Nrf2 were also upregulated. In the immune aspects, the mRNA expression levels of proinflammatory cytokines, such as interleukin-6 (il-6), interleukin-1ß (il-1ß) and nuclear factor-κB (nf-κb), were reduced but the expressions of anti-inflammatory cytokines, such as growth factor-ß (tgf-ß) and interleukin-10 (il-10), were enhanced in the head kidney and spleen tissues after oral administration with sea buckthorn. In terms of muscle fatty acid composition, the ratio of n-3 polyunsaturated fatty acid (PUFA)/n-6 PUFA was notably higher after administering sea buckthorn flavonoids than that of the glucose group (P < 0.05). CONCLUSION: This study demonstrated that oral administration of sea buckthorn powder and sea buckthorn flavonoids significantly enhanced the antioxidant capacity and immune response and improved the muscle fatty acid compositions in common carp, and also mitigated the adverse effects of glucose treatment to a certain extent. © 2024 Society of Chemical Industry.

A metabolomics study on carcinogenesis of ground-glass nodules.

Objective: This study aimed to identify differential metabolites and key metabolic pathways between lung adenocarcinoma (LUAD) tissues and normal lung (NL) tissues using metabolomics techniques, to discover potential biomarkers for the early diagnosis of lung cancer. Material and Methods: Forty-five patients with primary ground-glass nodules (GGN) identified on computed tomography imaging and who were willing to undergo surgery at Shanghai General Hospital from December 2021 to December 2022 were recruited to the study. All participants underwent video thoracoscopy surgery with segmental or wedge resection of the lung. Tissue samples for pathological examination were collected from the site of ground-glass nodules (GGN) lesion and 3 cm away from the lesion (NL). The pathology results were 35 lung adenocarcinoma (LUAD) cases (13 invasive adenocarcinoma, 14 minimally invasive adenocarcinoma, and eight adenocarcinoma in situ), 10 benign samples, and 45 NL tissues. For the untargeted metabolomics technique, 25 LUAD samples were assigned as the case group and 30 NL tissues as the control group. For the targeted metabolomics technique, ten LUAD samples were assigned as the case group and 15 NL tissues as the control group. Samples were analyzed by untargeted and targeted metabolomics, with liquid chromatography-tandem mass spectrometry detection used as part of the experimental procedure. Results: Untargeted metabolomics revealed 164 differential metabolites between the case and control groups, comprising 110 up regulations and 54 down regulations. The main metabolic differences found by the untargeted method were organic acids and their derivatives. Targeted metabolomics revealed 77 differential metabolites between the case and control groups, comprising 69 up regulations and eight down regulations. The main metabolic changes found by the targeted method were fatty acids, amino acids, and organic acids. The levels of organic acids such as lactic acid, fumaric acid, and malic acid were significantly increased in LUAD tissue compared to NL. Specifically, an increased level of L-lactic acid was found by both untargeted (variable importance in projection [VIP] = 1.332, fold-change [FC] = 1.678, q = 0.000) and targeted metabolomics (VIP = 1.240, FC = 1.451, q = 0.043). Targeted metabolomics also revealed increased levels of fumaric acid (VIP = 1.481, FC = 1.764, q = 0.106) and L-malic acid (VIP = 1.376, FC = 1.562, q = 0.012). Most of the 20 differential fatty acids identified were downregulated, including dodecanoic acid (VIP = 1.416, FC = 0.378, q = 0.043) and tridecane acid (VIP = 0.880, FC = 0.780, q = 0.106). Furthermore, increased levels of differential amino acids were found in LUAD samples. Conclusion: Lung cancer is a complex and heterogeneous disease with diverse genetic alterations. The study of metabolic profiles is a promising research field in this cancer type. Targeted and untargeted metabolomics revealed significant differences in metabolites between LUAD and NL tissues, including elevated levels of organic acids, decreased levels of fatty acids, and increased levels of amino acids. These metabolic features provide valuable insights into LUAD pathogenesis and can potentially serve as biomarkers for prognosis and therapy response.

AGCM-22, a novel cetuximab-based EGFR-targeting antibody-drug-conjugate with highly selective anti-glioblastoma efficacy.

The epidermal growth factor receptor (EGFR) has received significant attention as a potential target for glioblastoma (GBM) therapeutics in the past two decades. However, although cetuximab, an antibody that specifically targets EGFR, exhibits a high affinity for EGFR, it has not yet been applied in the treatment of GBM. Antibody-drug conjugates (ADCs) utilize tumor-targeting antibodies for the selective delivery of cytotoxic drugs, resulting in improved efficacy compared to conventional chemotherapy drugs. However, the effectiveness of cetuximab as a targeted antibody for ADCs in the treatment of GBM remains uncertain. In this study, we synthesized AGCM-22, an EGFR-targeted ADC derived from cetuximab, by conjugating it with the tubulin inhibitor monomethyl auristatin E (MMAE) using our Valine-Alanine Cathepsin B cleavable linker. In vitro experiments demonstrated that AGCM-22 effectively inhibited GBM cell proliferation through increased levels of apoptosis and autophagy-related cell death, whereas cetuximab alone had no anti-GBM effects. Additionally, both mouse and human orthotopic tumor models exhibited the selective tumor-targeting efficacy of AGCM-22, along with favorable metabolic properties and superior anti-GBM activity compared to temozolomide (TMZ). In summary, this study presents a novel ADC for GBM therapy that utilizes cetuximab as the tumor-targeting antibody, resulting in effective delivery of the cytotoxic drug payload.

Quality of life after pancreatic surgery.

BACKGROUND: Pancreatic surgery is challenging owing to the anatomical characteristics of the pancreas. Increasing attention has been paid to changes in quality of life (QOL) after pancreatic surgery. AIM: To summarize and analyze current research results on QOL after pancreatic surgery. METHODS: A systematic search of the literature available on PubMed and EMBASE was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant studies were identified by screening the references of retrieved articles. Studies on patients' QOL after pancreatic surgery published after January 1, 2012, were included. These included prospective and retrospective studies on patients' QOL after several types of pancreatic surgeries. The results of these primary studies were summarized inductively. RESULTS: A total of 45 articles were included in the study, of which 13 were related to pancreaticoduodenectomy (PD), seven to duodenum-preserving pancreatic head resection (DPPHR), nine to distal pancreatectomy (DP), two to central pancreatectomy (CP), and 14 to total pancreatectomy (TP). Some studies showed that 3-6 months were needed for QOL recovery after PD, whereas others showed that 6-12 months was more accurate. Although TP and PD had similar influences on QOL, patients needed longer to recover to preoperative or baseline levels after TP. The QOL was better after DPPHR than PD. However, the superiority of the QOL between patients who underwent CP and PD remains controversial. The decrease in exocrine and endocrine functions postoperatively was the main factor affecting the QOL. Minimally invasive surgery could improve patients' QOL in the early stages after PD and DP; however, the long-term effect remains unclear. CONCLUSION: The procedure among PD, DP, CP, and TP with a superior postoperative QOL is controversial. The long-term benefits of minimally invasive versus open surgeries remain unclear. Further prospective trials are warranted.

Design, Synthesis, and Structure-Activity Relationship of Novel Pyridazinone-Based PARP7/HDACs Dual Inhibitors for Elucidating the Relationship between Antitumor Immunity and HDACs Inhibition.

Histone deacetylases (HDACs) inhibitors such as vorinostat (SAHA) has been used to treat hematologic malignancies (rather than solid tumors) and have been found to suppress the JAK/STAT, a critical signal pathway for antitumor immunity, while PARP7 inhibitor RBN-2397 could activate the type I interferons (IFN-I) pathway, facilitating downstream effects such as STAT1 phosphorylation and immune activation. To elucidate whether simultaneous inhibition of these two targets could interfere with these two signal pathways, a series of pyridazinone-based PARP7/HDACs dual inhibitors have been designed, synthesized, and evaluated in vitro and in vivo experiments. Compound 9l was identified as a potent and balanced dual inhibitor for the first time, exhibiting excellent antitumor capabilities both in vitro and in vivo. This suggests that 9l can be used as a valuable tool molecule for investigating the relationship between anticancer immunity and HDAC inhibition.

The H2O2 Self-Sufficient 3D Printed ß-TCP Scaffolds with Synergistic Anti-Tumor Effect and Reinforced Osseointegration.

Tumor recurrence and massive bone defects are two critical challenges for postoperative treatment of oral and maxillofacial tumor, posing serious threats to the health of patients. Herein, in order to eliminate residual tumor cells and promote osteogenesis simultaneously, the hydrogen peroxide (H2O2) self-sufficient TCP-PDA-CaO2-CeO2 (TPCC) scaffolds are designed by preparing CaO2 or/and CeO2 nanoparticles (NPs)/chitosan solution and modifying the NPs into polydopamine (PDA)-modified 3D printed TCP scaffolds by rotary coating method. CaO2 NPs loaded on the scaffolds can release Ca2+ and sufficient H2O2 in the acidic tumor microenvironment (TME). The generated H2O2 can further produce hydroxyl radicals (·OH) under catalysis effect by peroxidase (POD) activity of CeO2 NPs, in which the photothermal effect of the PDA coating enhances its POD catalytic effect. Overall, NPs loaded on the scaffold chemically achieve a cascade reaction of H2O2 self-sufficiency and ·OH production, while functionally achieving synergistic effects on anti-tumor and bone promotion. In vitro and in vivo studies show that the scaffolds exhibit effective osteo-inductivity, induced osteoblast differentiation and promote osseointegration. Therefore, the multifunctional composite scaffolds not only validate the concept of chemo-dynamic therapy (CDT) cascade therapy, but also provide a promising clinical strategy for postoperative treatment of oral and maxillofacial tumor.

Performance evaluation of rhamnolipid biosurfactant produced by Pseudomonas aeruginosa and its effect on marine oil-spill remediation.

This study aimed to reveal that the effect of biosurfactant on the dispersion and degradation of crude oil. Whole genome analysis showed that Pseudomonas aeruginosa GB-3 contained abundant genes involved in biosurfactant synthesis and metabolic processes and had the potential to degrade oil. The biosurfactant produced by strain GB-3 was screened by various methods. The results showed that the surface tension reduction activity was 28.6 mN·m-1 and emulsification stability was exhibited at different pH, salinity and temperature. The biosurfactant was identified as rhamnolipid by LC-MS and FTIR. The fermentation conditions of strain GB-3 were optimized by response surface methodology, finally the optimal system (carbon source: glucose, nitrogen source: ammonium sulfate, C/N ratio:16:1, pH: 7, temperature: 30-35 °C) was determined. Compared with the initial fermentation, the yield of biosurfactant increased by 4.4 times after optimization. In addition, rhamnolipid biosurfactant as a dispersant could make the dispersion of crude oil reach 38% within seven days, which enhanced the bioavailability of crude oil. As a biostimulant, it could also improve the activity of indigenous microorganism and increase the degradation rate of crude oil by 10-15%. This study suggested that rhamnolipid biosurfactant had application prospect in bioremediation of marine oil-spill.

Retrospective analysis of Advanced Heart Failure and/or Cardiogenic Shock in Patients with Aortic Valve Stenosis Treated by Transcatheter Aortic Valve Replacement and a Nomogram Model Construction.

Objective: Currently, there is little information about the risk of sudden cardiac death and its predictors in aortic valve stenosis patients after transcatheter aortic valve replacement (TAVR). Therefore, we conducted a large sample cohort study on TAVR patients to evaluate the predictive factors and incidence of heart failure death caused by advanced heart failure (AHF) and sudden cardiac death. Furthermore, a nomogram model to predict its risk was constructed. Methods: This study retrospectively analyzed the data of 241 consecutive participants who had received TAVR treatment for aortic valve stenosis in our hospital from January 2020 to January 2022. The characteristics of the subjects, including myocardial zymogram, renal function, biochemical parameters, and cardiac ultrasound parameters, were collected. Moreover, a nomogram was constructed to predict the risk of sudden cardiac death and its predictors in patients after transcatheter aortic valve replacement (TAVR). The model was validatedinternally using measures of calibration and decision curve analysis. Results: Six independent risk factors(Age, smoking, diabetes, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and fasting blood glucose) were finally recruited into the nomogram model to predict the risk of advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR. Besides, the decision curve analysis and receiver operating characteristic curve indicated that the nomogram prediction models showed positive clinical benefits. Conclusions: The Age, smoking, diabetes, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and fasting blood glucose are the independent risk factors for advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR. The construction of nomograms is beneficial in predicting the risk of advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR.

The transcriptional control of LcIDL1-LcHSL2 complex by LcARF5 integrates auxin and ethylene signaling for litchi fruitlet abscission.

At the physiological level, the interplay between auxin and ethylene has long been recognized as crucial for the regulation of organ abscission in plants. However, the underlying molecular mechanisms remain unknown. Here, we identified transcription factors involved in indoleacetic acid (IAA) and ethylene (ET) signaling that directly regulate the expression of INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) and its receptor HAESA (HAE), which are key components initiating abscission. Specifically, litchi IDA-like 1 (LcIDL1) interacts with the receptor HAESA-like 2 (LcHSL2). Through in vitro and in vivo experiments, we determined that the auxin response factor LcARF5 directly binds and activates both LcIDL1 and LcHSL2. Furthermore, we found that the ETHYLENE INSENSITIVE 3-like transcription factor LcEIL3 directly binds and activates LcIDL1. The expression of IDA and HSL2 homologs was enhanced in LcARF5 and LcEIL3 transgenic Arabidopsis plants, but reduced in ein3 eil1 mutants. Consistently, the expressions of LcIDL1 and LcHSL2 were significantly decreased in LcARF5- and LcEIL3-silenced fruitlet abscission zones (FAZ), which correlated with a lower rate of fruitlet abscission. Depletion of auxin led to an increase in 1-aminocyclopropane-1-carboxylic acid (the precursor of ethylene) levels in the litchi FAZ, followed by abscission activation. Throughout this process, LcARF5 and LcEIL3 were induced in the FAZ. Collectively, our findings suggest that the molecular interactions between litchi AUXIN RESPONSE FACTOR 5 (LcARF5)-LcIDL1/LcHSL2 and LcEIL3-LcIDL1 signaling modules play a role in regulating fruitlet abscission in litchi and provide a long-sought mechanistic explanation for how the interplay between auxin and ethylene is translated into the molecular events that initiate abscission.

Research Progress on the NSP10 Protein of Porcine Reproductive and Respiratory Syndrome Virus.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious and pathogenic infectious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). It manifests as reproductive disorders in sows and respiratory disorders in piglets. PRRSV infects swine herds with symptoms such as abortions, stillbirths, and mummified fetuses in gestating sows. Piglets mainly experience abdominal respiration and respiratory symptoms. To date, the prevention of PRRS relies primarily on vaccination and the implementation of various preventive and control measures. Swine deaths caused by PRRS have resulted in significant economic losses to the pig industry worldwide. Non-structural protein 10 (NSP10) has helicase and adenosine triphosphatase (ATPase) activities that unwind DNA and RNA and play important roles in viral replication and transcription. Hence, it can be potentially used to develop novel reagents for the detection of PPRSV. This article reviews genetic variations, interaction with viral and host proteins, effects on PRRSV replication, immunomodulation, apoptosis, and viral virulence of NSP10, with the aim of providing a theoretical basis for the prevention and control of PRRS and drug development in the future.

Crevice Corrosion Behavior of 201 Stainless Steel in NaCl Solutions with Different pH Values by In Situ Monitoring.

Crevice corrosion (CC) behavior of 201 stainless steel (SS) in 1 M NaCl + x M HCl/y M NaOH solutions with various pH was investigated using SECM and optical microscopic observations. Results show that the CC was initiated by the decrease in pH value within the crevice. The pH value near the crevice mouth falls rapidly to 1.38 in the first 2 h in the strongly acidic solution, while the pH value was observed to rise firstly and then decrease in the neutral and alkaline solutions. It indicates there is no incubation phase in the CC evolution of 201-SS in a pH = 2.00 solution, while an incubation phase was observed in pH = 7.00 and 11.00 solutions. Additionally, there appeared to be a radial pH variation within the gap over time. The pH value is the lowest at the gap mouth, which is in line with the in situ optical observation result that the severely corroded region is at the mouth of the gap. The decrease in pH value inside results in the negative shift of open circuit potential (OCP) and the initiation of CC of 201-SS. The increased anodic dissolution rate in the acidic solution accelerates the breakdown of passive film inside, reducing the initiation time and stimulating the spread of CC.

Single-cell RNA sequencing in donor and end-stage heart failure patients identifies NLRP3 as a therapeutic target for arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Dilation may be the first right ventricular change and accelerates the progression of threatening ventricular tachyarrhythmias and heart failure for patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), but the treatment for right ventricular dilation remains limited. METHODS: Single-cell RNA sequencing (scRNA-seq) of blood and biventricular myocardium from 8 study participants was performed, including 6 end-stage heart failure patients with ARVC and 2 normal controls. ScRNA-seq data was then deeply analyzed, including cluster annotation, cellular proportion calculation, and characterization of cellular developmental trajectories and interactions. An integrative analysis of our single-cell data and published genome-wide association study-based data provided insights into the cell-specific contributions to the cardiac arrhythmia phenotype of ARVC. Desmoglein 2 (Dsg2)mut/mut mice were used as the ARVC model to verify the therapeutic effects of pharmacological intervention on identified cellular cluster. RESULTS: Right ventricle of ARVC was enriched of CCL3+ proinflammatory macrophages and TNMD+ fibroblasts. Fibroblasts were preferentially affected in ARVC and perturbations associated with ARVC overlap with those reside in genetic variants associated with cardiac arrhythmia. Proinflammatory macrophages strongly interact with fibroblast. Pharmacological inhibition of Nod-like receptor protein 3 (NLRP3), a transcriptional factor predominantly expressed by the CCL3+ proinflammatory macrophages and several other myeloid subclusters, could significantly alleviate right ventricular dilation and dysfunction in Dsg2mut/mut mice (an ARVC mouse model). CONCLUSIONS: This study provided a comprehensive analysis of the lineage-specific changes in the blood and myocardium from ARVC patients at a single-cell resolution. Pharmacological inhibition of NLRP3 could prevent right ventricular dilation and dysfunction of mice with ARVC.

Utilizing non-coding RNA-mediated regulation of ATP binding cassette (ABC) transporters to overcome multidrug resistance to cancer chemotherapy.

Multidrug resistance (MDR) is one of the primary factors that produces treatment failure in patients receiving cancer chemotherapy. MDR is a complex multifactorial phenomenon, characterized by a decrease or abrogation of the efficacy of a wide spectrum of anticancer drugs that are structurally and mechanistically distinct. The overexpression of the ATP-binding cassette (ABC) transporters, notably ABCG2 and ABCB1, are one of the primary mediators of MDR in cancer cells, which promotes the efflux of certain chemotherapeutic drugs from cancer cells, thereby decreasing or abolishing their therapeutic efficacy. A number of studies have suggested that non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play a pivotal role in mediating the upregulation of ABC transporters in certain MDR cancer cells. This review will provide updated information about the induction of ABC transporters due to the aberrant regulation of ncRNAs in cancer cells. We will also discuss the measurement and biological profile of circulating ncRNAs in various body fluids as potential biomarkers for predicting the response of cancer patients to chemotherapy. Sequence variations, such as alternative polyadenylation of mRNA and single nucleotide polymorphism (SNPs) at miRNA target sites, which may indicate the interaction of miRNA-mediated gene regulation with genetic variations to modulate the MDR phenotype, will be reviewed. Finally, we will highlight novel strategies that could be used to modulate ncRNAs and circumvent ABC transporter-mediated MDR.

Expression and Significance of Inflammatory Factors in Idiopathic Spinal Epidural Lipomatosis (Grade III).

BACKGROUND: Idiopathic spinal epidural lipomatosis (iSEL) is frequently associated with the utilization of steroids, endocrine disorders, obesity, and surgical interventions. Nevertheless, the pathogenesis of iSEL remains inadequately understood. The study aimed to investigate the contribution of inflammatory factors to idiopathic epidural lipomatosis. METHODS: Thirteen patients with iSEL (Grade III, iSEL group) and 12 patients with lumbar disc herniation (control group) who underwent unilateral biportal endoscopy from March 2020 to April 2023 were enrolled. Histological examination of adipose tissue was the performed to analyze expressions of pro-inflammatory cytokines (TNF-α, IL-1ß), and anti-inflammatory factors (arginase-1, IL-10) in serum and epidural adipose cells. RESULTS: Compared with the control group, the number of inflammatory cell infiltrations per field in HE-stained sections was significantly elevated, TNF-α and IL-1ß expression in adipocytes of epidural adipose tissue were markedly higher, and arginase-1 and IL-10 expression were significantly lower in the iSEL group (all p < 0.001). However, no statistically significant differences were observed in the serum level of TNF-α, IL-1ß, arginase-1, and IL-10 between the two groups (p = 0.963). In addition, there was also no significant disparity in adipocyte size between the two groups (p = 0.739). CONCLUSION: iSEL demonstrated elevated inflammatory cells and imbalance towards proinflammatory cytokines in adipocytes of epidural adipose tissue that may be associated with the pathogenesis of symptomatic iSEL. These data suggest that inflammatory response could be one of the mechanisms of iSEL. However, further multicenter epidemiological investigations and rigorous basic and clinical research are warranted to elucidate the specific etiology of iSEL.

Characteristic microbiome and synergistic mechanism by engineering agent MAB-1 to evaluate oil-contaminated soil biodegradation in different layer soil.

Bioremediation is a sustainable and pollution-free technology for crude oil-contaminated soil. However, most studies are limited to the remediation of shallow crude oil-contaminated soil, while ignoring the deeper soil. Here, a high-efficiency composite microbial agent MAB-1 was provided containing Bacillus (naphthalene and pyrene), Acinetobacter (cyclohexane), and Microbacterium (xylene) to be synergism degradation of crude oil components combined with other treatments. According to the crude oil degradation rate, the up-layer (63.64%), middle-layer (50.84%), and underlying-layer (54.21%) crude oil-contaminated soil are suitable for bioaugmentation (BA), biostimulation (BS), and biostimulation+bioventing (BS+BV), respectively. Combined with GC-MS and carbon number distribution analysis, under the optimal biotreatment, the degradation rates of 2-ring and 3-ring PAHs in layers soil were about 70% and 45%, respectively, and the medium and long-chain alkanes were reduced during the remediation. More importantly, the relative abundance of bacteria associated with crude oil degradation increased in each layer after the optimal treatment, such as Microbacterium (2.10-14%), Bacillus (2.56-12.1%), and Acinetobacter (0.95-12.15%) in the up-layer soil; Rhodococcus (1.5-6.9%) in the middle-layer soil; and Pseudomonas (3-5.4%) and Rhodococcus (1.3-13.2%) in the underlying-layer soil. Our evaluation results demonstrated that crude oil removal can be accelerated by adopting appropriate bioremediation approach for different depths of soil, providing a new perspective for the remediation of actual crude oil-contaminated sites.