Role of BACH1 in multiple myeloma.

OBJECTIVE: Examine Bach1 protein expression in bone marrow biopsy specimens obtained from newly diagnosed multiple myeloma (NDMM) and iron deficiency anemia (IDA) patients. Conduct a thorough analysis to explore the potential connection between Bach1 and the onset as well as treatment response of NDMM. METHODS: This study investigated Bach1 expression in bone marrow biopsy tissues from NDMM and IDA patients. Immunohistochemical staining and Image-pro Plus software were utilized for quantitatively obtaining the expression level of Bach1 protein. Arrange Bach1 expression levels from high to low, and use its median expression level as the threshold. Samples with Bach1 expression level above the median are categorized as the high-expression group, while those below the median are categorized as the low-expression group. Under this grouping, a detailed discussion was conducted to explore relationship of the Bach1 expression level with the patients' gender, ISS stage, and survival rate based on the Bortezomib (Btz) therapy. RESULTS: Our experiment indicates that the expression level of Bach1 in NDMM patients is significantly higher than in IDA patients. Furthermore, we discovered that patients in the high-expression group exhibit better prognosis compared to those in the low-expression group after Btz-treatment. Bioinformatics analysis further confirms this conclusion. CONCLUSION: By categorizing Bach1 expression level as high and low, our study offers a unique perspective on understanding the relationship between Bach1 and NDMM.

NCX1/Ca2+ promotes autophagy and decreases bortezomib activity in multiple myeloma through non-canonical NFκB signaling pathway.

Although bortezomib (BTZ) is the cornerstone of anti-multiple myeloma (MM) therapy, the inevitable primary and secondary drug resistance still seriously affects the prognosis of patients. New treatment strategies are in need. Sodium-calcium exchanger 1 (NCX1) is a calcium-permeable ion transporter on the membrane, and our previous studies showed that low NCX1 confers inferior viability in MM cells and suppressed osteoclast differentiation. However, the effect of NCX1 on BTZ sensitivity of MM and its possible mechanism remain unclear. In this study, we investigated the effect of NCX1 on BTZ sensitivity in MM, focusing on cellular processes of autophagy and cell viability. Our results provide evidence that NCX1 expression correlates with MM disease progression and low NCX1 expression increases BTZ sensitivity. NCX1/Ca2+ triggered autophagic flux through non-canonical NFκB pathway in MM cells, leading to attenuated the sensitivity of BTZ. Knockdown or inhibition of NCX1 could potentiate the anti-MM activity of BTZ in vitro and vivo, and inhibition of autophagy sensitized NCX1-overexpressing MM cells to BTZ. In general, this work implicates NCX1 as a potential therapeutic target in MM with BTZ resistance and provides novel mechanistic insights into its vital role in combating BTZ resistance.

Pleiotropic role of GAS6 in cardioprotection against ischemia-reperfusion injury.

INTRODUCTION: Myocardial ischemia-reperfusion (IR) injury is a common medical issue contributing to the onset and progression of ischemic heart diseases (IHD). Growth arrest-specific gene 6 (GAS6), a vitamin K-dependent secretory protein, promotes cell proliferation and inhibits inflammation and apoptosis through binding with Tyro3, Axl, and Mertk (TAM) receptors. OBJECTIVES: Our study aimed to examine the effect of GAS6 pathways activation as a potential new treatment in myocardial IR injury. METHODS: Gain- and loss-of-function experiments were utilized to determine the roles of GAS6 in the pathological processes of myocardial IR injury. RESULTS: Our results revealed down-regulated levels of GAS6, Axl, and SIRT1 in murine hearts subjected to IR injury, and cardiomyocytes challenged with hypoxia reoxygenation (HR) injury. GAS6 overexpression significantly improved cardiac dysfunction in mice subjected to myocardial IR injury, accompanied by reconciled mitochondrial dysfunction, oxidative stress, and apoptosis. In vitro experiments also observed a protective effect of GAS6 in cardiomyocytes. SIRT1 was found to function as a downstream regulator for GAS6/Axl signaling axis. Through screening a natural product library, a polyphenol natural compound catechin was identified to exhibit a protective effect by turning on GAS6/Axl-SIRT1 cascade. CONCLUSIONS: Together, our findings indicate that GAS6 emerges as a potential novel target in the management of myocardial IR injury and other related anomalies.

Metal-Organic Frameworks Possessing Suitable Pores for Xe/Kr Separation.

Adsorption separation of the Xe/Kr mixture remains a tough issue since Xe and Kr have an inert nature and similar sizes. Here we present a chlorinated metal-organic framework (MOF) [JXNU-19(Cl)] and its nonchlorinated analogue (JXNU-19) for Xe/Kr separation. The two isostructural MOFs constructed from the heptanuclear cobalt-hydroxyl clusters bridged by organic ligands are three-dimensional structures. Detailed contrast of the Xe/Kr adsorption separation properties of the MOF shows that significantly enhanced Xe uptakes and Xe/Kr adsorption selectivity (17.1) are observed for JXNU-19 as compared to JXNU-19(Cl). The main binding sites for Xe in the MOF revealed by computational simulations are far away from the chlorine sites, suggesting that the introduction of the chlorine groups results in the unfavorable Xe adsorption for JXNU-19(Cl). The optimal pores, high surface area, and multiple strong Xe-framework interactions facilitate the effective Xe/Kr separation for JXNU-19.

Pterostilbene protects against H2 O2 -induced oxidative stress by regulating GAS6/Axl signaling in HL-1 cells.

Pterostilbene (PTE, trans-3,5-dimethoxy-4'-hydroxystilbene), a natural plant polyphenol, possesses numerous pharmacological effects, including antioxidant, antidiabetic, antiatherosclerotic, and neuroprotective aspects. This study aims to investigate whether PTE plays a protective role against oxidative stress injury by GAS6/Axl signaling pathway in cardiomyocytes. Hydrogen peroxide (H2 O2 )-induced oxidative stress HL-1 cells were used as models. The mechanism by which PTE protected oxidative stress is investigated by combining cell viability, cell ROS levels, apoptosis assay, molecular docking, quantitative real-time PCR, and western blot analysis. GAS6 shRNA was performed to investigate the involvement of GAS6/Axl pathways in PTE's protective role. The results showed that PTE treatment improved the cell morphology and viability, and inhibited the apoptosis rate and ROS levels in H2 O2 -injured HL-1 cells. Particularly, PTE treatment upregulated the levels of GAS6, Axl, and markers related to oxidative stress, apoptosis, and mitochondrial function related. Molecular docking showed that PTE and GAS6 have good binding ability. Taken together, PTE plays a protective role against oxidative stress injury through inhibiting oxidative stress and apoptosis and improving mitochondrial function. Particularly, GAS6/Axl axis is the surprisingly prominent in the PTE-mediated pleiotropic effects.

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1ß, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators of many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, and inflammation. Accumulating evidence has shown that PGC-1s are implicated in many diseases, such as cancers, cardiac diseases and cardiovascular diseases, neurological disorders, kidney diseases, motor system diseases, and metabolic disorders. Examining the upstream modulators and co-activated partners of PGC-1s and identifying critical biological events modulated by downstream effectors of PGC-1s contribute to the presentation of the elaborate network of PGC-1s. Furthermore, discussing the correlation between PGC-1s and diseases as well as summarizing the therapy targeting PGC-1s helps make individualized and precise intervention methods. In this review, we summarize basic knowledge regarding the PGC-1s family as well as the molecular regulatory network, discuss the physio-pathological roles of PGC-1s in human diseases, review the application of PGC-1s, including the diagnostic and prognostic value of PGC-1s and several therapies in pre-clinical studies, and suggest several directions for future investigations. This review presents the immense potential of targeting PGC-1s in the treatment of diseases and hopefully facilitates the promotion of PGC-1s as new therapeutic targets.

Pentoxifylline protects against cerebral ischaemia-reperfusion injury through ferroptosis regulation via the Nrf2/SLC7A11/GPX4 signalling pathway.

OBJECTIVE: To investigate whether pentoxifylline (PTX) attenuates cerebral ischaemia-reperfusion injury (IRI) in rats by inhibiting ferroptosis and to explore the underlying molecular mechanisms. METHODS: Cerebral IRI was induced in male Sprague-Dawley (SD) rats using middle cerebral artery occlusion (MCAO). The effects of PTX on cerebral ischaemia-reperfusion brain samples were detected through neurological deficit score, staining and electron microscopy; levels of ferroptosis biomarkers from brain samples were detected using kits. Additionally, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), transferrin receptor protein 1, divalent metal transporter 1, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were determined by immunohistochemistry, real-time quantitative polymerase chain reaction and western blotting. RESULTS: Pre-treatment with PTX was found to improve neurological function, evidenced by reduced neurological deficit scores, decreased infarct volume and alleviated pathological features post-MCAO. This improvement was accompanied by reduced lipid peroxidation levels and mitigated mitochondrial damage. Notably, PTX's inhibitory effect on ferroptosis was characterised by enhanced Nrf2 nuclear translocation and regulation of ferroptosis-related proteins. Moreover, inhibition of Nrf2 using ML385 (an Nrf2-specific inhibitor) reversed PTX's neuroprotective effect on MCAO-induced ferroptosis via the SLC7A11/GPX4 signalling pathway. CONCLUSIONS: Ferroptosis is evident following cerebral ischaemia-reperfusion in rats. Pentoxifylline confers protection against IRI in rats by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signalling pathway.

SSBP1 is a novel prognostic marker and promotes disease progression via p38MAPK signaling pathway in multiple myeloma.

Multiple myeloma (MM) remains an incurable disease. Identification of meaningful co-expressed gene clusters or representative biomarkers of MM may help to identify new pathological mechanisms and promote the development of new therapies. Here, we performed weighted sgene co-expression network analysis and a series of bioinformatics analysis to identify single stranded DNA binding protein 1 (SSBP1) as novel hub gene associated with MM development and prognosis. In vitro, CRISPR/cas9 mediated knockdown of SSBP1 can significantly inhibit the proliferation of MM cells through inducing apoptosis and cell cycle arrest in G0/G1 phase. We also found that decreased SSBP1 expression significantly increased mitochondrial reactive oxygen species (mtROS) generation and the level of phosphorylated p38MAPK. Furthermore, it was further verified that disruption of SSBP1 expression could inhibit the tumor growth via p38MAPK pathway in a human myeloma xenograft model. In summary, our study is the first to demonstrate that SSBP1 promotes MM development by regulating the p38MAPK pathway.

GAS6 attenuates sepsis-induced cardiac dysfunction through NLRP3 inflammasome-dependent mechanism.

Sepsis is a major health threat and often results in heart failure. Growth arrest-specific gene 6 (GAS6), a 75-kDa vitamin K-dependent protein, participates in immune regulation and inflammation through binding to AXL (the TAM receptor family). This study was designed to examine the myocardial regulatory role of GAS6 in sepsis. Serum GAS6 levels were increased in septic patients and mice while myocardial GAS6 levels were decreased in septic mice. Single-cell RNA sequencing further revealed a decline in GAS6 levels of nearly all cell clusters including cardiomyocytes. GAS6 overexpression via adeno-associated virus 9 (AAV9) overtly improved cardiac dysfunction in cecum ligation and puncture (CLP)-challenged mice, along with alleviated mitochondrial injury, endoplasmic reticulum stress, oxidative stress, and apoptosis. However, GAS6-elicited beneficial effects were removed by GAS6 knockout. The in vitro study was similar to these findings. Our data also noted a downstream effector role for NLRP3 in GAS6-initiated myocardial response. GAS6 knockout led to elevated levels of NLRP3, the effect of which was reconciled by GAS6 overexpression. Taken together, these results revealed the therapeutical potential of targeting GAS6/AXL-NLRP3 signaling in the management of heart anomalies in sepsis.

PhyNEO: A Neural-Network-Enhanced Physics-Driven Force Field Development Workflow for Bulk Organic Molecule and Polymer Simulations.

An accurate, generalizable, and transferable force field plays a crucial role in the molecular dynamics simulations of organic polymers and biomolecules. Conventional empirical force fields often fail to capture precise intermolecular interactions due to their negligence of important physics, such as polarization, charge penetration, many-body dispersion, etc. Moreover, the parameterization of these force fields relies heavily on top-down fittings, limiting their transferabilities to new systems where the experimental data are often unavailable. To address these challenges, we introduce a general and fully ab initio force field construction strategy, named PhyNEO. It features a hybrid approach that combines both the physics-driven and the data-driven methods and is able to generate a bulk potential with chemical accuracy using only quantum chemistry data of very small clusters. Careful separations of long-/short-range interactions and nonbonding/bonding interactions are the key to the success of PhyNEO. By such a strategy, we mitigate the limitations of pure data-driven methods in long-range interactions, thus largely increasing the data efficiency and the scalability of machine learning models. The new approach is thoroughly tested on poly(ethylene oxide) and polyethylene glycol systems, giving superior accuracies in both microscopic and bulk properties compared to conventional force fields. This work thus offers a promising framework for the development of advanced force fields in a wide range of organic molecular systems.

Branched-chain amino acid catabolic defect promotes α-cell proliferation via activating mTOR signaling.

Elevated circulating level of branched-chain amino acids (BCAAs) is closely related to the development of type 2 diabetes. However, the role of BCAA catabolism in various tissues in maintaining glucose homeostasis remains largely unknown. Pancreatic α-cells have been regarded as amino acid sensors in recent years. Therefore, we generated α-cell specific branched-chain alpha-ketoacid dehydrogenase E1α subunit (BCKDHA) knockout (BCKDHA-αKO) mice to decipher the effects of BCAA catabolism in α-cells on whole-body energy metabolism. BCKDHA-αKO mice showed normal body weight, body fat, and energy expenditure. Plasma glucagon level and glucose metabolism also remained unchanged in BCKDHA-αKO mice. Whereas, the deletion of BCKDHA led to increased α-cell number due to elevated cell proliferation in neonatal mice. In vitro, only leucine among BCAAs promoted aTC1-6 cell proliferation, which was blocked by the agonist of BCAA catabolism BT2 and the inhibitor of mTOR Rapamycin. Like Rapamycin, BT2 attenuated leucine-stimulated phosphorylation of S6 in αTC1-6 cells. Elevated phosphorylation level of S6 protein in pancreatic α-cells was also observed in BCKDHA-αKO mice. These results suggest that local accumulated leucine due to defective BCAA catabolism promotes α-cell proliferation through mTOR signaling, which is insufficient to affect glucagon secretion and whole-body glucose homeostasis.

Astragaloside IV promotes cerebral angiogenesis and neurological recovery after focal ischemic stroke in mice via activating PI3K/Akt/mTOR signaling pathway.

Our previous work has shown that activating PI3K/Akt/mTOR signaling pathway is involved in angiogenesis after ischemic stroke, and recent studies have revealed that astragaloside IV (AS-IV) exerts beneficial effects on cerebral protection after ischemic stroke. However, it is unclear whether the beneficial effects of AS-IV against ischemic stroke is related to angiogenesis and PI3K/Akt/mTOR signaling pathway. The aim of this study was to investigate the effects of AS-IV on angiogenesis and long-term neurological recovery after focal ischemic stroke as well as the underlying mechanisms. After mice model of distal middle cerebral artery occlusion (dMCAO), AS-IV was administered with low dose (10 mg/kg), medium dose (20 mg/kg) or high dose (40 mg/kg) once daily for 14 days. We report herein that AS-IV (20 mg/kg) significantly ameliorated long-term neurological recovery and attenuated histological damage, while promoting cerebral blood flow recovery in ischemic mice. Moreover, AS-IV administration enhanced microvessel density as well as astrocyte and pericyte coverage around microvessels in the peri-infarct cortex. In vitro, AS-IV promoted endothelial cells (ECs) proliferation and tube formation after oxygen-glucose deprivation (OGD), which was partially inhibited by the specific PI3K inhibitor LY294002. Finally, AS-IV increased the expression of vascular endothelial growth factor (VEGF) through activating the PI3K/AKT/mTOR signaling pathway in the process of promoting angiogenesis. These results suggested that AS-IV may promote angiogenesis after ischemic stroke through increasing the expression of VEGF via PI3K/Akt/mTOR pathway, which unveils novel therapeutic effects of AS-IV and suggests promising application of AS-IV in ischemic stroke.

Ethyl pyruvate attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells: Role of GAS6/Axl signaling.

Background: Ischemic stroke, caused neurological dysfunction due to inadequate blood supply to brain, has a high morbidity and mortality. Ethyl pyruvate (EP), a simple aliphatic ester derived from pyruvic acid, has the advantages of safety and stability. Studies have confirmed that EP has anti-oxidative, anti-inflammation, anti-tumor, and other pharmacological effects, and it demonstrates significant therapeutic effects on multiple diseases. GAS6 and its high affinity Axl receptor play an important role in cell adhesion, anti-apoptosis, proliferation and migration by activating downstream signal transduction pathways. Previous studies have demonstrated the neuroprotective effects of the GAS6/Axl axis. Methods: A series of experimental methods were employed to confirm the effect of EP against cerebral hypoxia/reoxygenation (HR) injury. Results: In this study, the protective effect and mechanism of EP on HR injury in N2a cells was explored. The results found that treatment with EP could increase HR-injured neuronal viability, improve cell morphology, and reduce LDH release and ROS accumulation, thereby exhibiting a neuroprotective effect. Furthermore, EP treatment restored the down-regulated expression of GAS6, Axl, NQO1, PGC-1α, NRF1, and UCP2 caused by HR injury. Specifically, it was observed that the neuroprotective effect of EP was partially inhibited by GAS6 siRNA. Conclusion: In conclusion, these results suggest that EP treatment attenuates HR-induced oxidative stress injury in neuroblastoma cells via activating GAS6/Axl signaling.

Chemodivergent Synthesis of Benzothiadiazin-3-one 1-Oxides and Benzisothiazol-3-ones via Visible Light-Promoted Intramolecular N-S Bond Formation.

We reported a versatile protocol to chemodivergently construct significant heterocyclic scaffolds of benzothiadiazin-3-one 1-oxides and benzisothiazol-3-ones by visible light-promoted photocatalysis. This substrate-dependent chemoselective strategy enables N-(2-mercaptophenyl)-N'-substituted ureas through the N-S bond coupling/oxidation cascade to selectively produce benzothiadiazin-3-one 1-oxides; however, the transformation of 2-mercaptobenzamides only occurs via N-S bond coupling to access benzisothiazol-3-ones with moderate to good yields. This strategy features mild conditions, excellent chemoselectivity, and functional group compatibility, which has potential applications in organic and medicinal chemistry.

Value of enhanced recovery after surgery in patients undergoing endoscopic retrograde cholangiopancreatography with intravenous anaesthesia for choledocholithiasis: a retrospective observational study.

Introduction: Enhanced recovery after surgery (ERAS) is rarely used in minimally invasive endoscopic surgery, especially in endoscopic retrograde cholangiopancreatography (ERCP). Aim: This study evaluated the safety and efficacy of the ERAS protocol in patients undergoing ERCP for choledocholithiasis. Material and methods: The study had a retrospective design and included patients with biliary tract stones who underwent ERCP between June 2019 and November 2022. Patients who received the ERAS protocol between June 2021 and November 2022 were enrolled as an ERAS group, and those who received traditional perioperative treatment between December 2019 and May 2021 were enrolled as a control group. Results: A total of 349 patients were enrolled (ERAS group, n = 185; control group, n = 164). The cannulation and stone extraction success rates were significantly higher in the ERAS group than in the control group (p < 0.05). The incidence of postoperative pancreatitis was significantly lower in the ERAS group (p = 0.02), but there were no significant differences in other complications. The postoperative hospital stay was significantly shorter in the ERAS group than in the control group (p < 0.001), with no statistically significant differences in costs according to surgical period, or in total costs, between the 2 groups. Conclusions: Application of the ERAS protocol is safe and feasible in patients undergoing ERCP for choledocholithiasis. The ERAS protocol can accelerate recovery, reduce postoperative pain, and shorten the hospital stay without increasing the cost of treatment.

Distinct non-synonymous mutations in cytochrome b highly correlate with decoquinate resistance in apicomplexan parasite Eimeria tenella.

BACKGROUND: Protozoan parasites of the genus Eimeria are the causative agents of chicken coccidiosis. Parasite resistance to most anticoccidial drugs is one of the major challenges to controlling this disease. There is an urgent need for a molecular marker to monitor the emergence of resistance against anticoccidial drugs, such as decoquinate. METHODS: We developed decoquinate-resistant strains by successively exposing the Houghton (H) and Xinjiang (XJ) strains of E. tenella to incremental concentrations of this drug in chickens. Additionally, we isolated a decoquinate-resistant strain from the field. The resistance of these three strains was tested using the criteria of weight gain, relative oocyst production and reduction of lesion scores. Whole-genome sequencing was used to identify the non-synonymous mutations in coding genes that were highly associated with the decoquinate-resistant phenotype in the two laboratory-induced strains. Subsequently, we scrutinized the missense mutation in a field-resistant strain for verification. We also employed the AlphaFold and PyMOL systems to model the alterations in the binding affinity of the mutants toward the drug molecule. RESULTS: We obtained two decoquinate-resistant (DecR) strains, DecR_H and XJ, originating from the original H and XJ strains, respectively, as well as a decoquinate-resistant E. tenella strain from the field (DecR_SC). These three strains displayed resistance to 120 mg/kg decoquinate administered through feed. Through whole-genome sequencing analysis, we identified the cytochrome b gene (cyt b; ETH2_MIT00100) as the sole mutated gene shared between the DecR_H and XJ strains and also detected this gene in the DecR_SC strain. Distinct non-synonymous mutations, namely Gln131Lys in DecR_H, Phe263Leu in DecR_XJ, and Phe283Leu in DecR_SC were observed in the three resistant strains. Notably, these mutations were located in the extracellular segments of cyt b, in close proximity to the ubiquinol oxidation site Qo. Drug molecular docking studies revealed that cyt b harboring these mutants exhibited varying degrees of reduced binding ability to decoquinate. CONCLUSIONS: Our findings emphasize the critical role of cyt b mutations in the development of decoquinate resistance in E. tenella. The strong correlation observed between cyt b mutant alleles and resistance indicates their potential as valuable molecular markers for the rapid detection of decoquinate resistance.

Fecal Metagenomics Study Reveals That a Low-Fiber Diet Drives the Migration of Wild Asian Elephants in Xishuangbanna, China.

The rare northward migration of wild Asian elephants in Xishuangbanna, China, has attracted global attention. Elephant migration is a complex ecological process, and the factors driving this long-distance migration remain elusive. In this study, fresh fecal samples were collected from both captive and wild Asian elephants, along with breastfed calves residing within the Wild Elephant Valley of Xishuangbanna. Our aim was to investigate the relationship between diet, gut microbiota, and migration patterns in Asian elephants through comprehensive metagenomic sequencing analyses. Among the breastfed Asian elephant group, Bacteroidales and Escherichia emerged as the dominant bacterial taxa, while the primary carbohydrate-active enzymes (CAZymes) enriched in this group were GH2, GH20, GH92, GH97, GH38, GH23, and GH43, aligning with their dietary source, namely breast milk. The bacterial taxa enriched in captive Asian elephants (CAEs) were mainly Butyrivibrio, Treponema, and Fibrobacter, and the enriched lignocellulose-degrading enzymes mainly included GH25, GH10, GH9, and cellulase (EC 3.2.1.4). These findings are consistent with the high-fiber diet of captive elephants. In contrast, the main bacterial taxa enriched in wild Asian elephants (WAEs) were Ruminococcus and Eubacterium, and the enriched CAZymes included GH109, GH20, GH33, GH28, GH106, and GH39. The abundance of lignocellulose-degrading bacteria and CAZyme content was low in WAEs, indicating challenges in processing high-fiber foods and explaining the low-fiber diet in this group. These findings suggest that wild elephant herds migrate in search of nutritionally suitable, low-fiber food sources.

PIK3CG Regulates NLRP3/GSDMD-Mediated Pyroptosis in Septic Myocardial Injury.

Cardiac insufficiency is a common complication of sepsis with high mortality. Inflammatory programmed cell death (pyroptosis) executed by NLRP3/gasdermin D (GSDMD) is intrinsically correlated with septic myocardial injury. However, it remains unclear whether PIK3CG, a classical target of septic myocardial injury, can affect pyroptosis by regulating NLRP3/GSDMD signaling. In this study, a series of experimental methods were used to observe the effect of PIK3CG on NLRP3/GSDMD-mediated pyroptosis in Cecal ligation and puncture (CLP)-injured BALB/c mice and lipopolysaccharide (LPS)-injured HL-1 cardiomyocytes. Transcriptome analysis of CLP-injured myocardium revealed a regulatory relationship between PIK3CG and NLRP3/GSDMD signaling, which was further verified in clinical myocardium samples from GEO database. Both in vitro and in vivo experiments showed that the protein and mRNA levels of PIK3CG, GSDMD, NLRP3, IL-1ß, Caspase-1, and IL-18 were significantly increased. Importantly, PIK3CG siRNA was found to improve these changes, while PIK3CG overexpression worsened them. Notably, pyroptosis induced by CLP in the myocardium was reversed by the PIK3CG inhibitor (AS-604850). In conclusion, PIK3CG activates NLRP3 inflammasomes, thus promoting pyroptosis in septic myocardial injury.

The diagnostic value of ultrasound on different-sized thyroid nodules based on ACR TI-RADS.

OBJECTIVES: The thyroid nodule is one of the most common endocrine system diseases. Risk classification models based on ultrasonic features have been created by multiple professional societies, including the American College of Radiology (ACR), which published the Thyroid Imaging Reporting and Data System (TI-RADS) in 2017. The effect of the size in the diagnostic value of ultrasound remains not well defined. The purposes of our study aims to explore diagnostic value of the ACR TI-RADS on different-sized thyroid nodules. METHODS: A total of 1183 thyroid nodules were selected from 952 patients with thyroid nodules confirmed by surgical pathology from January 2021 to October 2022. Based on the maximum diameters of the nodules, they were stratified into groups A ( ≤ 10 mm), B ( > 10 mm, < 20 mm) and C ( ≥ 20 mm). The ultrasonic features of the thyroid nodules in each group were evaluated and scored based on ACR TI-RADS, and the receiver operating characteristic curve (ROC) was plotted to determine the optimal cut-off value for the ACR TI-RADS scores and categories in each group. Finally, the diagnostic efficacy of ACR TI-RADS on different-sized thyroid nodules was analyzed. RESULTS: Among the 1183 thyroid nodules, 340 were benign, 10 were low-risk and 833 were malignant. For the convenience of statistical analysis, low-risk thyroid nodules were classified as malignant in this study. The ACR TI-RADS scores and categorical levels of malignant thyroid nodules in each group were higher than those of benign ones (p < 0.05). The areas under the ROCs (AUCs) plotted based on scores were 0.741, 0.907, and 0.904 respectively in the three groups, and the corresponding optimal cut-off values were > 6 points, > 5 points and > 4 points respectively. While the AUCs of the ACR TI-RADS categories were 0.668, 0.855, and 0.887 respectively in each group, with the optimal cut-off values were all > TR4. Besides, for thyroid nodules of larger sizes, ACR TI-RADS exhibited weaker sensitivity with lower positive prediction value (PPV), but the specificity and negative prediction value (NPV) were both higher, presenting with statistically significant differences (p < 0.05). CONCLUSION: For thyroid nodules of different sizes, the diagnostic efficacy of ACR TI-RADS varies as well. The system shows better diagnostic efficacy on thyroid nodules of > 10 mm than on those ≤ 10 mm. Considering the favorable prognosis of thyroid microcarcinoma and the low diagnostic efficacy of ACR TI-RADS on it, the scoring and classification of thyroid micro-nodules can be left out in appropriate cases, so as to avoid the over-diagnosis and over-treatment of thyroid microcarcinoma to a certain extent.

Degradation of organic pollutants through activating bisulfite with lanthanum ferrite-loaded biomass carbon.

The removal of methylene blue (MB) in water is a challenging task due to its toxicity, carcinogenicity and resistance to biodegradation. Accordingly, a novel composite catalyst (BC@LF) was prepared by loading lanthanum ferrite (LaFeO3) on biomass carbon (BC) to activate bisulfite (BS) for methylene MB removal in this study. Characterization via scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) indicated that LaFeO3 was successfully loaded on BC. X-ray photoelectron spectroscopy (XPS) analysis suggested that [triple bond, length as m-dash]Fe(iii) was the main active site for BS activation. It was found that 99.4% MB was removed within 60 min in BC@LF/BS system. Sulfate radical (SO4˙-) and hydroxyl radicals (HO˙) were proved to be responsible for MB removal in the BC@LF/BS system and SO5˙- might also be involved in MB removal. The degradation efficiency of MB in the BC@LF/BS system decreased with increasing pH, while the adsorption efficiency of BC@LF for MB improved with increasing pH. Additionally, BC@LF exhibited good reusability for BS activation in successive uses. The BC@LF/BS system exhibited favorable removal effect for various organic compounds, indicating that it has good applicability in the treatment of organic wastewater.