Unravelling the Photoelectrochemical Water Splitting of Nanometer-Thick Carbon Nitride Layer.

Matching the thickness of the graphitic carbon nitride (CN) nanolayer with the charge diffusion length is expected to compensate for the poor intrinsic conductivity and charge recombination in CN for photoelectrochemical cells (PEC). Herein, the compact CN nanolayer with tunable thickness is in situ coated on carbon fibers. The compact packing along with good contact with the substrate improves the electron transport and alleviates the charge recombination. The PEC investigation shows CN nanolayer of 93 nm-thick yields an optimum photocurrent of 116 µA cm-2 at 1.23 V versus RHE, comparable to most micrometer-thick CN layers, with a low onset potential of 0.2 V in 1 m KOH under 1 sun illumination. This optimum performance suggests the electron diffusion length matches with the thickness of the CN nanolayer. Further deposition of NiFe-layered double hydroxide enhanced the surface water oxidation kinetics, delivering an improved photocurrent of 210 µA cm-2 with IPCE of 12.8% at 400 nm. The CN nanolayer also shows extended potential in PEC organic synthesis. This work experimentally reveals the PEC behavior of the nanometer-thick CN layer, providing new insights into CN in the application of energy and environment-related fields.

Neurotoxicity from long-term exposure to 6-PPDQ: Recent advances.

The recent acceleration of industrialization and urbanization has brought significant attention to N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6-PPDQ), an emerging environmental pollutant from tire wear, due to its long-term effects on the environment and organisms. Recent studies suggest that 6-PPDQ can disrupt neurotransmitter synthesis and release, impact receptor function, and alter signaling pathways, potentially causing oxidative stress, inflammation, and apoptosis. This review investigates the potential neurotoxic effects of prolonged 6-PPDQ exposure, the mechanisms underlying its cytotoxicity, and the associated health risks. We emphasize the need for future research, including precise exposure assessments, identification of individual differences, and development of risk assessments and intervention strategies. This article provides a comprehensive overview of 6-PPDQ's behavior, impact, and neurotoxicity in the environment, highlighting key areas and challenges for future research.

Hydrophobic Carbon Nitride Nanolayer Enables High-Flux Oil/Water Separation with Photocatalytic Antifouling Ability.

Efficient oil/water separation tackles various issues in occasions of oil leakage and oil discharge, such as environmental pollution, recollection of the oil, and saving the water. Herein, a compact superhydrophobic/superoleophilic graphitic carbon nitride nanolayer coated on carbon fiber networks (CNBA/CF) is designed and synthesized for efficient gravity-driven oil/water separation. The CNBA/CF shows excellent oil absorption and an impressive oil/water filtration separation performance. The flux reaches the state-of-art value of 4.29 × 105 L/m2/h for dichloromethane with separation efficiency up to 99%. Successive oil absorption tests, long-term filtration separation, and harsh conditions experiments confirm the remarkable separation and chemical structure stability of the CNBA/CF filter. Besides, the CNBA/CF demonstrates good photocatalytic antifouling ability thanks to the extended visible light absorption and improved charge separation. This work combines the material surface wettability modulation with a photocatalytic self-cleaning property in the fabrication of efficient oil/water separation materials while overcoming the filter fouling issue.

Defining multistep cell fate decision pathways during pancreatic development at single-cell resolution.

The generation of terminally differentiated cell lineages during organogenesis requires multiple, coordinated cell fate choice steps. However, this process has not been clearly delineated, especially in complex solid organs such as the pancreas. Here, we performed single-cell RNA-sequencing in pancreatic cells sorted from multiple genetically modified reporter mouse strains at embryonic stages E9.5-E17.5. We deciphered the developmental trajectories and regulatory strategies of the exocrine and endocrine pancreatic lineages as well as intermediate progenitor populations along the developmental pathways. Notably, we discovered previously undefined programs representing the earliest events in islet α- and ß-cell lineage allocation as well as the developmental pathway of the "first wave" of α-cell generation. Furthermore, we demonstrated that repressing ERK pathway activity is essential for inducing both α- and ß-lineage differentiation. This study provides key insights into the regulatory mechanisms underlying cell fate choice and stepwise cell fate commitment and can be used as a resource to guide the induction of functional islet lineage cells from stem cells in vitro.

Oxymatrine Alleviates Hyperglycemic Cerebral Ischemia/Reperfusion Injury via Protecting Microvessel.

Hyperglycemia aggravates cerebral ischemia/reperfusion (I/R) injury via vascular injury. There is still a lack of effective pharmaceutical preparations for cerebral I/R injury under hyperglycemia. This study aimed to investigate the effects of oxymatrine (OMT) on hyperglycemia-exacerbated cerebral I/R injury in vitro and in vivo. The middle cerebral artery occlusion (MCAO) and reperfusion was established in the rats under hyperglycemia. Meanwhile, oxygen-glucose deprivation and reoxygenation (OGD/R) with high glucose was used as an in vitro model of hyperglycemic cerebral I/R injury. The results showed that the neurological deficit score, mortality, infarct volume and penumbra apoptosis in hyperglycemia group were significantly higher than those in normal glucose group. OMT pre-treated obviously reduced the degree of neurological deficit, mortality, infarct volume, improve cerebral blood flow after I/R in rats with hyperglycemia, and increase the survival rate of human brain microvascular endothelial cells (HBMECs) in high glucose and OGD/R group. OMT significantly improved the ultrastructure changes of endothelial cells, and maintain the migration and angiogenesis potency of HBMECs in high glucose and OGD/R group. OMT obviously alleviated the down-regulating CD31 and CD105 expression in cerebral microvessels caused by hyperglycemia. It is concluded that OMT treatment might alleviate cerebral I/R injury under hyperglycemia via protecting microvessels.

The biological function and clinical significance of STIL in osteosarcoma.

BACKGROUND: SCL/TAL1 interrupting locus (STIL) is associated with the progression of several tumors; however, the biological role of STIL in osteosarcoma remains poorly understood. METHODS: In this study, the clinical significance of STIL in osteosarcoma was analyzed by gene chip data recorded in public databases. STIL expression was silenced in osteosarcoma cell lines to observe the effects on proliferation, apoptosis, invasion, and migration. Differentially expressed genes (DEGs) in the osteosarcoma chip were analyzed using The Limma package, and STIL co-expressed genes were obtained via the Pearson correlation coefficient. The potential molecular mechanism of STIL in osteosarcoma was further explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. RESULTS: Osteosarcoma was associated with higher STIL expression compared to the control samples, and the standardized mean difference (SMD) was 1.52. STIL also had a good ability to distinguish osteosarcoma from non-osteosarcoma samples [area under the curve (AUC) = 0.96]. After silencing STIL, osteosarcoma cell proliferation decreased, apoptosis increased, and the migratory and invasion ability decreased. A total of 294 STIL differentially co-expressed genes were screened, and a bioinformatics analysis found that differentially co-expressed genes were primarily enriched in the cell signaling pathways. The protein-protein interaction (PPI) network indicated that the hub differentially co-expressed genes of STIL were CDK1, CCNB2, CDC20, CCNA2, BUB1, and AURKB. CONCLUSIONS: STIL is associated with osteosarcoma proliferation and invasion, and may be promote the progression of osteosarcoma by regulating the expression of CDK1, CCNB2, CDC20, CCNA2, BUB1 and AURKB.

Uncoupling Protein 2 Deficiency Enhances NLRP3 Inflammasome Activation Following Hyperglycemia-Induced Exacerbation of Cerebral Ischemia and Reperfusion Damage In Vitro and In Vivo.

Mitochondrial uncoupling protein 2 (UCP2) deficiency exacerbates brain damage following cerebral ischemia/reperfusion (I/R). The Nod-like receptor protein-3 (NLRP3) inflammasome also plays a vital role in cerebral I/R damage. However, the effect of UCP2 on NLRP3 inflammasome-mediated hyperglycemia and I/R damage is not clear. In the present study, UCP2-knockout (UCP2-/-) and wild-type (WT) mice were used to establish a model of middle cerebral artery occlusion (MCAO) and reperfusion under normo- and hyperglycemic conditions. HT22 cells were established as a model of oxygen-glucose deprivation and reoxygenation (OGD/R) with high glucose to mimic hyperglycemia and I/R in vitro. HT22 cells were treated with/without different concentrations of the UCP2-specific inhibitor genipin for different periods of time. The results showed that UCP2 deficiency significantly increased histopathological changes and apoptosis after cerebral I/R damage in hyperglycemic mice. Moreover, UCP2 deficiency enhanced NLRP3 inflammasome activation in neurons when cerebral I/R damage was exacerbated by hyperglycemia. Furthermore, UCP2 deficiency enhanced NLRP3 inflammasome activation and reactive oxygen species (ROS) production in HT22 cells under OGD/R and high-glucose conditions. UCP2 deficiency aggravated hyperglycemia-induced exacerbation of cerebral I/R damage. UCP2 deficiency also enhanced NLRP3 inflammasome activation and ROS production in neurons in vitro and in vivo. These findings suggest that UCP2 deficiency enhances NLRP3 inflammasome activation following hyperglycemia-induced exacerbation of cerebral I/R damage in vitro and in vivo. UCP2 may be a potential therapeutic target for hyperglycemia-induced exacerbation of cerebral I/R damage.

Abnormal amplitude of low frequency fluctuation and functional connectivity in non-neuropsychiatric systemic lupus erythematosus: a resting-state fMRI study.

PURPOSE: To explore the amplitude of low frequency fluctuation (ALFF) and functional connectivity (FC) disorders in non-neuropsychiatric systemic lupus erythematosus (non-NPSLE) patients by resting-state functional magnetic resonance imaging (rs-fMRI) and to study whether there are some clinical biomarkers that can be used to monitor the brain dysfunction. METHODS: Based on the rs-fMRI data of 36 non-NPSLE patients and 30 normal controls, we first obtained the regions with abnormal ALFF signals in non-NPSLE patients. Then, by taking these areas as seed regions of interest (ROIs), we calculated the FC between ROIs and the whole brain to assess the network-level alterations. Finally, we correlated the altered values of ALFF and FC in non-NPSLE patients to some clinical data. RESULTS: Compared with the controls, non-NPSLE patients showed decreased ALFF in bilateral precuneus and increased ALFF in right cuneus and right calcarine fissure surrounding cortex (CAL). At network level, non-NPSLE patients exhibited higher FC between left precuneus and left middle occipital gyrus (MOG)/left superior occipital gyrus (SOG)/right middle frontal gyrus (MFG)/right dorsolateral superior frontal gyrus (SFGdor), and higher FC between right cuneus and bilateral precuneus/left posterior cingulate gyrus (PCG). The abnormal ALFF in right CAL and abnormal FC in right cuneus-left precuneus, right cuneus-right precuneus, and right cuneus-left PCG were correlated with the patients' certain clinical data (p < 0.05). CONCLUSION: Rs-fMRI is a promising tool for detecting the brain function disorders in non-NPSLE patients and to help understand the neurophysiological mechanisms. C4 and Systemic Lupus Erythematosus Disease Activity Index may be biomarkers of brain dysfunction in non-NPSLE patients.

Regulation of IL-17 by lncRNA of IRF-2 in the pearl oyster.

Long noncoding RNAs (lncRNAs), once thought to be nonfunctional, have recently been shown to participate in the multilevel regulation of transcriptional, posttranscriptional and epigenetic modifications and to play important roles in various biological processes, including immune responses. However, the expression and roles of lncRNAs in invertebrates, especially nonmodel organisms, remain poorly understood. In this study, by comparing a transcriptome to the PfIRF-2 genomic structure, we identified lncIRF-2 in the PfIRF-2 genomic intron. The results of the RNA interference (RNAi) and the nucleus grafting experiments indicated that PfIRF-2 might have a negative regulatory effect on lncIRF-2, and PfIRF-2 and lncIRF-2 may have a positive regulatory effect on PfIL-17. Additionally, lncIRF-2, PfIRF-2 and PfIL-17 were involved in responses to the nucleus graft. These results will enhance the knowledge of lncIRF-2, IRF-2, and IL-17 functions in both pearl oysters and other invertebrates.

[Efficacy of compound Dendrobium on PI3K/AKT/eNOS signaling pathway in hypertensive rats induced by "dietary disorders"].

To observe the efficacy of compound Dendrobium on Sprague Dawley rats (SD) hypertension model induced by "dietary disorders" and its relevant mechanism, totally 50 SD rats were fed with high-sugar, high-fat diet and alcohol for four weeks. According to the blood pressure after modeling, the rats were divided into model group, valsartan group (8 mg·kg⁻¹), low, medium and high-dose Dendrobium candidum compound groups (1.65, 3.30, 5.00 g·kg⁻¹), with 10 rats in each group, and the other 10 SD rats were also taken as the normal group. After four weeks of treatment, blood pressure was measured. Orbital blood was collected for the determination of serum cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL), calculation of atherosclerosis index (AI). Nitric acid reductase method was used to detect serum nitric oxide (NO); the levels of serum endothelin-1 (ET-1) and intercellular adhesion molecule-1 (ICAM-1) were measured by ELISA. The rats were put to death after the last administration, and the protein expressions of PI3K/AKT/eNOS in thoracic aorta of rats in each group were detected by Western blot. The aorta was separated and stained with hematoxylin-eosin (HE) to observe the changes in the endothelium and blood vessels in the thoracic aorta. Masson staining was used to observe the formation of aortic collagen. The expressions of nitric oxide synthase (eNOS) and ICAM-1 in aortic endothelial cells were observed by immunohistochemistry. In contrast, the results show D. candidum compound can significantly reduce the blood pressure in hypertensive rats, increase HDL-c, and reduce AI, while increasing serum NO content, decreasing ET-1 and ICAM-1 levels and promoting PI3K/AKT/NOS protein expressions. The lesion degree of the D. candidum compound group was reduced, and the collagen deposition was significantly reduced. Meanwhile, D. candidum compound can significantly increase the expression of eNOS, and reduce the formation of ICAM-1.Therefore, D. candidum compound has an obvious antihypertensive effect on hypertensive rats, which may be related to the increase in PI3K/AKT/eNOS signaling pathways and NO generation, the inhibition of the secretion of ICAM-1 and ET-1, the protection of the vascular endothelium and the improvement of aortic disease.

Cloning and gene expression of signal transducers and activators of transcription (STAT) homologue provide new insights into the immune response and nucleus graft of the pearl oyster Pinctada fucata.

The signal transducers and activators of the transcription (STAT) family play an important role in regulatory and cellular functions by regulating the expression of a variety of genes, including cytokines and growth factors. In the present study, a Pinctada fucata STAT protein, termed PfSTAT, was described. The deduced amino acid sequence of PfSTAT contains the conserved STAT_bind domain and the SH2 domain, and the additional Bin/Amphiphysin/Rvs (BAR) domain, but does not have STAT_alpha and STAT_int domains. Multiple sequence alignments revealed that PfSTAT showed relatively low identity with vertebrate and other invertebrate STATs, and phylogenetic analysis indicated that the evolution of STAT may have been more complex and ancient. Gene expression analysis revealed that PfSTAT is involved in the immune response to polyinosinic-polycytidylic acid (poly I:C) stimulation and in the nucleus insertion operation. This study contributes to a better understanding of PfSTAT in protecting the pearl oyster from disease or injury caused by grafting.

Nuclear factor of activated T cells (NFAT) in pearl oyster Pinctada fucata: molecular cloning and functional characterization.

Nuclear factor of activated T cells (NFAT) plays an important role in nonimmune cells and also in T cells and many other cells of the immune system, by regulating the expression of a variety of genes involved in the immune response, organ development, developmental apoptosis and angiogenesis. In the present study, the NFAT homology gene, PfNFAT, from the pearl oyster Pinctada fucata was cloned and its genomic structure and promoter were analyzed. PfNFAT encodes a putative protein of 1226 amino acids, and contains a highly conserved Rel homology region (RHR) with DNA-binding specificity, and a regulatory domain (NFAT homology region, NHR) containing a potent transactivation domain (TAD). The PfNFAT gene consists of 12 exons and 11 introns, and its promoter contains potential binding sites for transcription factors such as NF-κB (Nuclear factor κB), STATx (signal transducer and activator of transcription), AP-1 (activator protein-1) and Sox-5/9 (SRY type HMG box-5/9), MyoD (Myogenic Differentiation Antigen) and IRF (Interferon regulatory factor). Comparison and phylogenetic analysis revealed that PfNFAT shows high identity with other invertebrate NFAT, and clusters with the NFAT5 subgroup. Furthermore, gene expression analysis revealed that PfNFAT is involved in the immune response to lipopolysaccharide (LPS) and Polyinosinic-polycytidylic acid (poly I:C) stimulation and in the nucleus inserting operation. The study of PfNFAT may increase understanding of molluscan innate immunity.

Wellens syndrome caused by spasm of the proximal left anterior descending coronary artery.

Electrocardiographic characteristics of Wellens syndrome (WS) consist of deeply inverted T waves or biphasic T waves in anterior precordial leads. Studies have shown that patients with WS have critical stenosis or complete obstruction of the proximal left anterior descending coronary artery (LAD) and high risk for the development of extensive anterior myocardial infarction. Here, we reported a case presenting with WS and with a small plaque in the proximal LAD and slow flow in the LAD other than significant stenosis of the proximal LAD detected by coronary angiography. The mechanisms for WS of our case are discussed.

Continuous passive motion for preventing venous thromboembolism after total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is a common form of orthopaedic surgery. Venous thromboembolism (VTE), which consists of deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major and potentially fatal complication after TKA. The incidence of DVT after TKA is 40% to 80% and the incidence of PE is approximately 2%. It is generally agreed that thromboprophylaxis should be used in patients who undergo TKA. Both pharmacological and mechanical methods are used in the prevention of DVT. Pharmacological methods alter the blood coagulation profile and may increase the risk of bleeding complications. When pharmacological methods cannot be used the mechanical methods become crucial for VTE prophylaxis. Continuous passive motion (CPM) is provided through an external motorised device which enables a joint to move passively throughout a preset arc of motion. Despite the theoretical effectiveness and widespread use of CPM, there are still differing views on the effectiveness of CPM as prophylaxis against thrombosis after TKA. This is an update of the review first published in 2012. OBJECTIVES: The aim of this review was to determine the effectiveness of continuous passive motion (CPM) therapy for preventing venous thromboembolism (VTE) in patients after total knee arthroplasty (TKA). SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014), CENTRAL (2014, Issue 1), Ovid MEDLINE (to week 1 February 2014) and EMBASE (to Week 07 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the use of CPM with control in preventing DVT or PE after TKA. People aged 18 years and older who had undergone TKA were included in this review. We excluded studies of patients who presented with DVT at baseline. The experimental and control groups received similar postoperative care and therapy other than the CPM. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the citations retrieved by the search strategies for reports of relevant RCTs. They independently selected trials that satisfied the inclusion criteria, extracted data and undertook quality assessment. Effects were estimated as risk ratios (RRs), mean differences or standardised mean differences with 95% confidence intervals (CIs). Meta-analyses were performed using a fixed-effect model for continuous variables. Where heterogeneity existed (determined by the I(2) statistic) a random-effects model was used. MAIN RESULTS: Eleven RCTs involving 808 participants met the inclusion criteria. The methodological quality of the included studies was variable and most of the predefined outcomes were reported by only one or two studies, therefore the quality of the evidence was low. Five studies with a total of 405 patients reported the incidence of DVT. In the CPM group (205 patients) 36 developed DVT (18%) compared to 29 (15%) in the control group (200 patients). The results of the meta-analysis showed no evidence that CPM had any effect on preventing VTE after TKA (RR 1.22, 95% CI 0.84 to 1.79). One trial (150 participants) did not find PE in any of the patients during hospitalisation or in the subsequent three months. PE was not reported in the other included studies. None of the trials reported deaths among the included participants. AUTHORS' CONCLUSIONS: There is not enough evidence from the available RCTs to conclude that CPM reduces VTE after TKA. We cannot assess the effect of CPM on mortality because no such events occurred amongst the participants of these trials. The quality of the evidence was low. The results are supported by only a small number of studies, most of which are of low to moderate quality.

Different types of intermittent pneumatic compression devices for preventing venous thromboembolism in patients after total hip replacement.

BACKGROUND: Total hip replacement (THR) is an effective treatment for reducing pain and improving function and quality of life in patients with hip disorders. While this operation is very successful, deep vein thrombosis (DVT) and pulmonary embolism (PE) are significant complications after THR. Different types of intermittent pneumatic compression (IPC) devices have been used for thrombosis prophylaxis in patients following THR. Available devices differ in compression garments, location of air bladders, patterns of pump pressure cycles, compression profiles, cycle length, duration of inflation time and deflation time, or cycling mode such as automatic or constant cycling devices. Despite the widely accepted use of IPC for the treatment of arterial and venous diseases, the relative effectiveness of different types of IPC systems as prophylaxis against thrombosis after THR is still unclear. OBJECTIVES: To assess the comparative effectiveness and safety of different IPC devices with respect to the prevention of venous thromboembolism in patients after THR. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Coordinator searched the Specialised Register (November 2014), CENTRAL (2014, Issue 10). Clinical trial databases were searched for details of ongoing and unpublished studies. Reference lists of relevant articles were also screened. There were no limits imposed on language or publication status. SELECTION CRITERIA: Randomized and quasi-randomized controlled studies were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreement was resolved by discussion or, if necessary, referred to a third review author. MAIN RESULTS: Only one quasi-randomized controlled study with 121 study participants comparing two types of IPC devices met the inclusion criteria. The authors found no cases of symptomatic DVT or PE in either the calf-thigh compression group or the plantar compression group during the first three weeks after the THR. The calf-thigh pneumatic compression was more effective than plantar compression for reducing thigh swelling during the early postoperative stage. The strength of the evidence in this review is weak as only one trial was included and it was classified as having a high risk of bias. AUTHORS' CONCLUSIONS: There is a lack of evidence from randomized controlled trials to make an informed choice of IPC device for preventing venous thromboembolism (VTE) following total hip replacement. More research is urgently required, ideally a multicenter, properly designed RCT including a sufficient number of participants. Clinically relevant outcomes such as mortality, imaging-diagnosed asymptomatic VTE and major complications must be considered.

Cronkhite-Canada syndrome complicated with pulmonary embolism: A case report.

BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare disease, that causes gastrointestinal polyps, ectodermal abnormalities, and gastrointestinal symptoms. CCS is prone to thromboembolism, but clinical workers have not yet established a clinical consciousness of preventing thromboembolism. The present case illustrates pulmonary embolism (PE) complicated by CCS. CASE SUMMARY: A 46-year-old male patient presented with mucus, purulent, and bloody stool. Ectodermal changes included skin pigmentation, alopecia, and nail dystrophy. Colonoscopy revealed the presence of multiple polyps. After a comprehensive evaluation, the patient was diagnosed with CCS. During the disease, he was also diagnosed with pulmonary embolism, Riehl's melanosis, and intestinal flora imbalance. After symptomatic treatment with omeprazole, mesalazine, rivaroxaban, nutritional support, and regulation of intestinal flora, the patient's symptoms were significantly relieved. CONCLUSION: CCS complicated with PE was reported for the first time in China in this study. Despite the fact that CCS is extremely rare, patients with CCS should be classified as a high-risk venous thromboembolism (VTE) population, and emphasis should be placed on venous thromboembolism risk assessment and stratification, deep venous thromboembolism screening, prevention of VTE, and careful long-term follow-up.

Comprehensive analysis of the clinical significance and molecular mechanism of T-box transcription factor 3 in osteosarcoma.

Background: T-box transcription factor 3 (TBX3) has been implicated in various malignant tumors, while its exact involvement in osteosarcoma (OS) remains unknown. Methods: Utilizing microarray data and bulk and single-cell RNA-seq data and qRT-PCR, we compared TBX3 mRNA expression levels in different stages of OS. Diagnostic ability testing and prognosis analysis were conducted to better understand the clinical importance of TBX3. Enrichment analysis was performed using gene groups with biological functions similar to TBX3 in different stages of OS to investigate the potential role of TBX3 in OS progression. In addition, we predicted medications targeted at TBX3 and identified downstream target genes to gain a comprehensive understanding of its therapeutic direction and regulatory mechanism. Results: TBX3 expression was highly upregulated in OS and was predominantly expressed in osteoblastic OS cells, with higher expression levels in metastatic tissues. TBX3 expression appeared somewhat suitable for discriminating between OS and normal samples, as well as different stages of OS. We found that TBX3 increased the malignant development of OS by altering cell cycle and cell adhesion molecules; exisulind and tacrolimus, which are targeted small-molecule medicines, were anticipated to counteract this dysregulation. The expression of CCNA2 could potentially be regulated by TBX3, contributing to OS advancement. Conclusion: TBX3 emerges as a potential biomarker for OS. In-depth research into its underlying molecular processes may offer new perspectives on treating OS.

Recent advances in potential therapeutic targets of ferroptosis­associated pathways for the treatment of stroke (Review).

Stroke is a severe neurological disease that is associated with high rates of morbidity and mortality, and the underlying pathological processes are complex. Ferroptosis fulfills a significant role in the progression and treatment of stroke. It is well established that ferroptosis is a type of programmed cell death that is distinct from other forms or types of cell death. The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with mechanisms inherent to stroke development. Inducers and inhibitors of ferroptosis have been shown to exert a role in the onset of this cell death process. Furthermore, it has been shown that interfering with ferroptosis affects the occurrence of stroke, indicating that targeting ferroptosis may offer a promising therapeutic approach for treating patients of stroke. Hence, the present review aimed to summarize the latest progress that has been made in terms of using therapeutic interventions for ferroptosis as treatment targets in cases of stroke. It provides an overview of the relevant pathways and molecular mechanisms that have been investigated in recent years, highlighting the roles of inducers and inhibitors of ferroptosis in stroke. Additionally, the intervention potential of various types of Traditional Chinese Medicine is also summarized. In conclusion, the present review provides a comprehensive overview of the potential therapeutic targets afforded by ferroptosis­associated pathways in stroke, offering new insights into how ferroptosis may be exploited in the treatment of stroke.

Upregulated dual oxidase 1-induced oxidative stress and caspase-1-dependent pyroptosis reflect the etiologies of heart failure.

BACKGROUND: Oxidative stress is implicated in the pathogenesis of heart failure. Dual oxidase 1 (DUOX1) might be important in heart failure development through its mediating role in oxidative stress. This study was designed to evaluate the potential role of DUOX1 in heart failure. MATERIALS AND METHODS: AC16 cells were treated with 2 µmol/L of doxorubicin (DOX) for 12, 24, and 48 h to construct a heart failure model. DUOX1 overexpression and silencing in AC16 cell were established. DUOX1 expression was detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Pyroptosis and reactive oxygen species (ROS) production were measured by flow cytometry. RESULTS: Increased DUOX1 expression levels were observed after DOX treatment for 24 h in AC16 cells. DUOX1 silencing inhibited DOX-induced pyroptosis and ROS production. The release of IL-1ß, IL-18, and lactate dehydrogenase (LDH), and expression levels of pyroptosis-related proteins were also decreased. DUOX1 overexpression increased pyroptosis, ROS production, IL-1ß, IL-18, and LDH release, and pyroptosis-related protein expression. N-acetyl-cysteine (NAC) significantly reversed DUOX1-induced pyroptosis, ROS, and related factors. CONCLUSION: These results suggest that DUOX1-derived genotoxicity could promote heart failure development. In the process, oxidative stress and pyroptosis may be involved in the regulation of DUOX1 in heart failure.

Clinical Significance and Potential Mechanisms of the RNA Methyltransferase KIAA1429 in Osteosarcoma.

Background: KIAA1429, a member of the RNA methyltransferase complex, is involved in cancer progression; however, the clinical significance and underlying mechanism of KIAA1429 in osteosarcoma (OS) remains to be reported. Methods: We evaluated the clinical significance of KIAA1429 in OS by performing RT-qPCR, microarray, and RNA sequencing and using published data as a reference. Two KIAA1429-targeting siRNA constructs were transfected into SW1353 cells. CCK-8 assay, colony formation assays, flow cytometry and the xenograft mouse model were conducted to investigate the biological function of KIAA1429 in OS. Results: The mRNA expression of KIAA1429 was markedly upregulated in 250 OS samples as compared to that in 71 non-cancer samples (standardized mean difference = 0.67). Summary receiver operating characteristic curve analysis revealed that KIAA1429 exhibited reliable diagnostic capacity to differentiate OS samples from non-cancer samples (area under the curve = 0.83). Further, survival analysis indicated that KIAA1429 overexpression was associated with shorter overall survival time. Knocking down KIAA1429 reduced m6A methylation levels, inhibited proliferation, prevented the growth of tumors in vivo and accelerated apoptosis of OS cells. In total, 395 KIAA1429-related genes were identified among co-expressed genes and differentially expressed genes, which were enriched in the cell cycle pathway. Protein-protein interaction network analysis showed that CDK1, CCNA2, and CCNB1 were KIAA1429-related genes, serving as major network hubs in OS. Conclusions: Our findings indicate that KIAA1429 plays an oncogenic role in OS and potentially facilitates OS progression via a mechanism that involves regulating CDK1, CCNA2, and CCNB1.