A photoelectrochemical aptasensor based on double Z-scheme α-Fe2O3/MoS2/Bi2S3 ternary heterojunction for sensitive detection of circulating tumor cells.

A novel photoelectrochemical (PEC) aptasensor based on a dual Z-scheme α-Fe2O3/MoS2/Bi2S3 ternary heterojunction for the ultrasensitive detection of circulating tumor cells (CTCs) was developed. The α-Fe2O3/MoS2/Bi2S3 nanocomposite was prepared via a step-by-step route, and the photoproduced electron/hole transfer path was speculated by conducting trapping experiments of reactive species. α-Fe2O3/MoS2/Bi2S3-modified electrodes exhibited greatly enhanced photocurrent under visible light due to the double Z-scheme charge transfer process, which met the requirement of the PEC sensor for detecting larger targets. After the aptamer was conjugated on the photoelectrode through chitosan (CS) and glutaraldehyde (GA), when MCF-7 cells were presented and captured, the photocurrent of the PEC biosensing system decreased due to steric hindrance. The current intensity had a linear relationship with the logarithm of MCF-7 cell concentration ranging from 10 to 1×105 cells mL-1, with a low detection limit of 3 cell mL-1 (S/N = 3). The dual Z-scheme α-Fe2O3/MoS2/Bi2S3 ternary heterojunction-modified PEC aptasensor exhibited high sensitivity and excellent specificity and stability. Additionally, MCF-7 cells in human serum were determined by this PEC aptasensor, exhibiting great potential as a promising tool for clinical detection.

SORBS1 inhibits epithelial to mesenchymal transition (EMT) of breast cancer cells by regulating PI3K/AKT signaling and macrophage phenotypic polarization.

This study aimed to explore the regulatory role of SORBS1 in macrophage polarization and the PI3K/AKT signaling pathway, as well as analyze its mechanism in epithelial-mesenchymal transition (EMT) of breast cancer cells. We established SORBS1-overexpressing and knockout cell lines and verified the effects of SORBS1 on cell viability, invasion, and migration by phenotyping experiments and assaying the expression of associated proteins. Furthermore, we established a breast cancer cell and macrophage co-culture system to validate the effect of SORBS1 expression on macrophage polarization and killing of breast cancer cells. Bioinformatics analysis showed that SORBS1 was lowly expressed in breast cancer (BRCA) samples and highly expressed in healthy tissues. Decreased SORBS1 expression was associated with poor prognosis, and the PI3K/AKT signaling pathway was the most significantly enriched pathway. In vitro experiments showed that high expression of SORBS1 inhibited the migration of breast cancer cells, as well as the PI3K/AKT signaling pathway, and blocked EMT of these cells. In addition, SORBS1 induced macrophage polarization to the M1-type and enhanced the killing effect on breast cancer cells in the co-culture system. In conclusion, we successfully verified that SORBS1 inhibits the invasion and migration of breast cancer cells, induces macrophage M1-type polarization, and blocks EMT of breast cancer cells, and it may act by regulating the PI3K/AKT signaling pathway.

Effects of Herpud1 in Methamphetamine-Induced Neuronal Apoptosis.

INTRODUCTION: Methamphetamine (METH) is an illicit psychoactive substance that can damage various organs in the body, especially the nervous system. We hypothesized that expression of homocysteine-inducible endoplasmic reticulum-resident with ubiquitin-like domain member 1 (Herpud1) protein would alleviate the induction of apoptosis following METH administration. METHODS: To test this hypothesis, we analysed the changes in Herpud1 expression and apoptosis in PC12 cells under different concentrations and exposure times of METH. Moreover, we examined the effects of Herpud1 knockdown on METH-induced neuronal apoptosis. Flow cytometry and Western blot analyses were used to evaluate apoptosis levels and the expression of apoptotic markers (cleaved caspase-3) in PC12 cells following Herpud1 knockdown by synthetic small interfering RNA (siRNA). RESULTS: Our results showed that Herpud1 expression was upregulated in PC12 cells following METH treatment, while endoplasmic reticulum stress (ERS) and apoptosis were also increased. Conversely, Herpud1 knockdown reduced METH-induced ERS and apoptosis levels in vitro. CONCLUSIONS: These results suggest that Herpud1 plays an essential role in METH-induced neuronal ERS and apoptosis and may represent a potential therapeutic gene target in METH-induced neurotoxicity.

Anion-Bridged Dual Hydrogen Bond Enabled Concerted Addition of Phenol to Glycal.

A noncovalent organocatalytic concerted addition of phenol to glycal is developed for the stereoselective and regioselective construction of biologically important phenolic 2-deoxyglycosides, featuring wide substrate tolerance. The method relies on an anion-bridged dual hydrogen bond interaction which is experimentally proved by Nuclear Magnetic Resonance (NMR), Ultraviolet and visible (UV-vis), and fluorescence analysis. Experimental evidence including kinetic analysis, Kinetic Isotope Effect (KIE) studies, linear free energy relationship, Hammett plot, and density functional theory (DFT) calculations is provided for a concerted mechanism where a high-energy oxocarbenium ion is not formed. In addition, the potential utility of this method is further demonstrated by the synthesis of biologically active glycosylated flavones. The benchmarking studies demonstrate significant advances in this newly developed method compared to previous approaches.

The Role of Sgt1 in Methamphetamine/Hyperthermia-induced Necroptosis.

INTRODUCTION: Methamphetamine (METH) is a synthetic drug widely abused globally and can result in hyperthermia (HT) and psychiatric symptoms. Our previous studies showed that heat shock protein 90 alpha (HSP90α) plays a vital role in METH/HT-elicited neuronal necroptosis; however, the detailed mechanism of HSP90α regulation remained obscure. METHODS: Herein, we demonstrated a function of the suppressor of G-two allele of SKP1 (Sgt1) in METH/HT-induced necroptosis. Sgt1 was mainly expressed in neurons, co-located with HSP90α, and increased in rat striatum after METH treatment. METH/HT injury triggered necroptosis and increased Sgt1 expression in PC-12 cells. RESULT: Data from computer simulations indicated that Sgt1 might interact with HSP90α. Geldanamycin (GA), the specific inhibitor of HSP90α, attenuated the interaction between Sgt1 and HSP90α. Knockdown of Sgt1 expression did not affect the expression level of HSP90α. Still, it inhibited the expression of receptor-interacting protein 3 (RIP3), mixed lineage kinase domain-like protein (MLKL), p-RIP3, and p-MLKL, as well as necroptosis induced by METH/HT injury. CONCLUSION: In conclusion, Sgt1 may regulate the expression of RIP3, p-RIP3, MLKL, and p-MLKL by assisting HSP90α in affecting the METH/HT-induced necroptotic cell death.

Multigene testing panels reveal pathogenic variants in sporadic breast cancer patients in northern China.

Background: Breast cancer, the most prevalent malignancy in women worldwide, presents diverse onset patterns and genetic backgrounds. This study aims to examine the genetic landscape and clinical implications of rare mutations in Chinese breast cancer patients. Methods: Clinical data from 253 patients, including sporadic and familial cases, were analyzed. Comprehensive genomic profiling was performed, categorizing identified rare variants according to the American College of Medical Genetics (ACMG) guidelines. In silico protein modeling was used to analyze potentially pathogenic variants' impact on protein structure and function. Results: We detected 421 rare variants across patients. The most frequently mutated genes were ALK (22.2%), BARD1 (15.6%), and BRCA2 (15.0%). ACMG classification identified 7% of patients harboring Pathogenic/Likely Pathogenic (P/LP) variants, with one case displaying a pathogenic BRCA1 mutation linked to triple-negative breast cancer (TNBC). Also identified were two pathogenic MUTYH variants, previously associated with colon cancer but increasingly implicated in breast cancer. Variants of uncertain significance (VUS) were identified in 112 patients, with PTEN c.C804A showing the highest frequency. The role of these variants in sporadic breast cancer oncogenesis was suggested. In-depth exploration of previously unreported variants led to the identification of three potential pathogenic variants: ATM c.C8573T, MSH3 c.A2723T, and CDKN1C c.C221T. Their predicted impact on protein structure and stability suggests a functional role in cancer development. Conclusion: This study reveals a comprehensive overview of the genetic variants landscape in Chinese breast cancer patients, highlighting the prevalence and potential implications of rare variants. We emphasize the value of comprehensive genomic profiling in breast cancer management and the necessity of continuous research into understanding the functional impacts of these variants.

A Robust Copper-Catalyzed Cross-Coupling of Glycosyl Thiosulfonate and Boronic Acids Enables the Construction of Thioglycosides.

An efficient and stereoretentive copper-catalyzed cross-coupling of glycosyl thiosulfonate and boronic acid for the construction of thioglycosides is described. The good functional group compatibility of this method allows the preparation of many bioactive aryl/alkenyl thioglycosides, including the hSGLT1 inhibitor.

Preparation and Photocatalytic Performance of MoS2/MoO2 Composite Catalyst.

Solar energy is an inexhaustible clean energy providing a key solution to the dual challenges of energy and environmental crises. Graphite-like layered molybdenum disulfide (MoS2) is a promising photocatalytic material with three different crystal structures, 1T, 2H and 3R, each with distinct photoelectric properties. In this paper, 1T-MoS2 and 2H-MoS2, which are widely used in photocatalytic hydrogen evolution, were combined with MoO2 to form composite catalysts using a bottom-up one-step hydrothermal method. The microstructure and morphology of the composite catalysts were studied by XRD, SEM, BET, XPS and EIS. The prepared catalysts were used in the photocatalytic hydrogen evolution of formic acid. The results show that MoS2/MoO2 composite catalysts have an excellent catalytic effect on hydrogen evolution from formic acid. By analyzing the photocatalytic hydrogen production performance of composite catalysts, it suggests that the properties of MoS2 composite catalysts with different polymorphs are distinct, and different content of MoO2 also bring differences. Among the composite catalysts, 2H-MoS2/MoO2 composite catalysts with 48% MoO2 content show the best performance. The hydrogen yield is 960 µmol/h, which is 1.2 times pure 2H-MoS2 and two times pure MoO2. The hydrogen selectivity reaches 75%, which is 22% times higher than that of pure 2H-MoS2 and 30% higher than that of MoO2. The excellent performance of the 2H-MoS2/MoO2 composite catalyst is mainly due to the formation of the heterogeneous structure between MoS2 and MoO2, which improves the migration of photogenerated carriers and reduces the possibilities of recombination through the internal electric field. MoS2/MoO2 composite catalyst provides a cheap and efficient solution for photocatalytic hydrogen production from formic acid.

Analysis of land subsidence caused by hydrodynamic force in Loess Hilly and gully region based on SBAS-InSAR.

After large-scale land consolidation in hilly loess region of the Loess Plateau in China, land subsidence has a wide affecting area and considerable difficulty of prevention. Hence, large-scale, stabilized, and continuous deformation monitoring is urgently needed for slopes. In this study, land consolidation zone in the loess platform area of Weinan, China, was selected as the object, and the 30-scene Sentinel-1A data in Jan, 2018 to Dec, 2019 were analyzed. The mean annual velocity of ground deformation was from -6.19 mm∙a-1 to 3.86 mm∙a-1, and Accumulated deformation velocity was within -8.49 mm∙a-1 to 7.24 mm∙a-1. Accumulated deformation of land consolidation changed with the seasons changing. The interrelationship between the spatiotemporal variations in ground subsidence and the precipitation, ground water, loess engineering properties was also discussed. Accumulated deformation of land consolidation changed with the seasons changing. The precipitation accelerated the subsidence by unexpected strong precipitation reflects that the infiltration of rainwater can lead to compacted loess deformation which caused by moistening effect. Under varying ground water environment, external loads may lead to soil collapse, resulting in non-uniform land subsidence. Co-compression deformation of original loess and compacted loess is main influencing factors of subsidence. These findings have important implications and significant positive effects on the prevention of potential hazard such as subsidence and side slope slip.

Inhibition of mitochondrial VDAC1 oligomerization alleviates apoptosis and necroptosis of retinal neurons following OGD/R injury.

Ischemia-reperfusion (I/R) injury is a common pathological mechanism in many retinal diseases, which can lead to cell death via mitochondrial dysfunction. Voltage-dependent anion channel 1 (VDAC1), which is mainly located in the outer mitochondrial membrane, is the gatekeeper of mitochondria. The permeability of mitochondrial membrane can be regulated by controlling the oligomerization of VDAC1. However, the functional mechanism of VDAC1 in retinal I/R injury was unclear. Our results demonstrate that oxygen-glucose deprivation and re-oxygenation (OGD/R) injury leads to apoptosis, necroptosis, and mitochondrial dysfunction of R28 cells. The OGD/R injury increases the levels of VDAC1 oligomerization. Inhibition of VDAC1 oligomerization by VBIT-12 rescued mitochondrial dysfunction by OGD/R and also reduced apoptosis/necroptosis of R28 cells. In vivo, the use of VBIT-12 significantly reduced aHIOP-induced neuronal death (apoptosis/necroptosis) in the rat retina. Our findings indicate that VDAC1 oligomers may open and enlarge mitochondrial membrane pores during OGD/R injury, leading to the release of death-related factors in mitochondria, resulting in apoptosis and necroptosis. This study provides a potential therapeutic strategy against ocular diseases caused by I/R injury.

PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons.

PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis, apoptosis, and necroptosis, which simultaneously occur during the pathophysiological process of infectious and inflammatory diseases. Although our previous literature mining study suggested that PANoptosis might occur in neuronal ischemia/reperfusion injury, little experimental research has been reported on the existence of PANoptosis. In this study, we used in vivo and in vitro retinal neuronal models of ischemia/reperfusion injury to investigate whether PANoptosis-like cell death (simultaneous occurrence of pyroptosis, apoptosis, and necroptosis) exists in retinal neuronal ischemia/reperfusion injury. Our results showed that ischemia/reperfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in vivo. Ischemia/reperfusion injury also significantly upregulated caspase-1, caspase-8, and NLRP3 expression, which are important components of the PANoptosome. These results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.

Surface Dynamic Damage Prediction Model of Horizontal Coal Seam Based on the Idea of Wave Lossless Propagation.

According to traditional concepts, the movement of overlying strata and surface damage caused by coal mining in horizontal coal seams are symmetrical in terms of spatial distribution. However, in a lot of engineering practices, this symmetry has not been discovered. We often use the symmetry function to establish the profile prediction function of the surface damage, which results in a large difference between the prediction result and the actual situation. To solve this problem, this paper takes subsidence velocity as an example. Firstly, the spatial distribution functions of subsidence velocity on both sides were deduced theoretically. Through comparison, it is found that the change rate of the spatial distribution curve of the coal pillar side subsidence velocity is smoother than that of the goaf side and the subsidence velocity curves are skewed to the left. Secondly, based on the idea of lossless propagation of harmonic waves and idealizing the propagation environment, the spatial propagation relationship of surface subsidence velocity in the time domain is established. Then, the Box-Cox transform function is introduced to improve the normal distribution probability density function, and a new dynamic subsidence prediction model based on the Box-Cox transformation is obtained, which is suitable for the full mining stage. The model is tested by practical cases, the prediction accuracy is better than 7%, and the prediction results can meet the needs of engineering prediction accuracy (10%). The results of this research can enrich the existing subsidence prediction theory and provide theoretical and technical support for the prediction of dynamic surface damage caused by similar mining.

Do pyroptosis, apoptosis, and necroptosis (PANoptosis) exist in cerebral ischemia? Evidence from cell and rodent studies.

Some scholars have recently developed the concept of PANoptosis in the study of infectious diseases where pyroptosis, apoptosis and necroptosis act in consort in a multimeric protein complex, PANoptosome. This allows all the components of PANoptosis to be regulated simultaneously. PANoptosis provides a new way to study the regulation of cell death, in that different types of cell death may be regulated at the same time. To test whether PANoptosis exists in diseases other than infectious diseases, we chose cerebral ischemia/reperfusion injury as the research model, collected articles researching cerebral ischemia/reperfusion from three major databases, obtained the original research data from these articles by bibliometrics, data mining and other methods, then integrated and analyzed these data. We selected papers that investigated at least two of the components of PANoptosis to check its occurrence in ischemia/reperfusion. In the cell model simulating ischemic brain injury, pyroptosis, apoptosis and necroptosis occur together and this phenomenon exists widely in different passage cell lines or primary neurons. Pyroptosis, apoptosis and necroptosis also occurred in rat and mouse models of ischemia/reperfusion injury. This confirms that PANoptosis is observed in ischemic brain injury and indicates that PANoptosis can be a target in the regulation of various central nervous system diseases.

Comprehensive analysis of N6-methylandenosine regulators and m6A-related RNAs as prognosis factors in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies and has been a leading cause of cancer-related death worldwide in recent years. N6-methyladenosine (m6A) methylation is the most abundant epigenetic modification of various types of RNAs, and it plays a vital role in promoting cancer development. Here, we obtained SNV and transcriptome data of CRC from The Cancer Genome Atlas (TCGA). We demonstrated that most m6A methylation regulators were aberrantly expressed in individuals with CRC. The abnormal expression of m6A regulators was caused by their different copy number variation (CNV) patterns, and alteration of m6A regulators was significantly correlated with prognosis and tumor stage. By using weighted coexpression network analysis (WGCNA), we identified m6A-related long noncoding RNAs (lncRNAs) and mRNAs; then we used least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct m6A-related lncRNA and mRNA prognostic signatures in the TCGA dataset. Furthermore, a nomogram with clinicopathological features, lncRNA risk scores, and mRNA risk scores was established, which showed a strong ability to forecast the overall survival of the individuals with CRC in training and testing sets. In conclusion, m6A methylation regulators played a vital role in affecting the prognosis of subjects with CRC, and m6A-related lncRNAs and mRNAs revealed underlying mechanisms in CRC tumorigenesis and progression.

Forensic examination and application of areca nuts as material evidence.

In this study, we aimed to explore the possibility of DNA analysis of areca nut as material evidence and the value of short tandem repeat (STR) typing of areca nut as material evidence under the condition of simulating external environment. In this study, water soaking, soil burial, sun exposure, and wet environment were used to treat areca nut residues. Chelex 100 was used to extract DNA, the PowerPlex21 kit to amplify, and the ABI PRISM® 310 Genetic Analyzer to analyze the DNA of areca nut residues. DNA and STR typing were performed to analyze the residue after chewing. The results showed that the number of residual sites decreased with time under the conditions of water soaking, soil burial, sun exposure, and wet environment. Thus, areca nut can be used as forensic material evidence for DNA analysis and individual identification.

The Role of HSP90α in Methamphetamine/Hyperthermia-Induced Necroptosis in Rat Striatal Neurons.

Methamphetamine (METH) is one of the most widely abused synthetic drugs in the world. The users generally present hyperthermia (HT) and psychiatric symptoms. However, the mechanisms involved in METH/HT-induced neurotoxicity remain elusive. Here, we investigated the role of heat shock protein 90 alpha (HSP90α) in METH/HT (39.5°C)-induced necroptosis in rat striatal neurons and an in vivo rat model. METH treatment increased core body temperature and up-regulated LDH activity and the molecular expression of canonical necroptotic factors in the striatum of rats. METH and HT can induce necroptosis in primary cultures of striatal neurons. The expression of HSP90α increased following METH/HT injuries. The specific inhibitor of HSP90α, geldanamycin (GA), and HSP90α shRNA attenuated the METH/HT-induced upregulation of receptor-interacting protein 3 (RIP3), phosphorylated RIP3, mixed lineage kinase domain-like protein (MLKL), and phosphorylated MLKL. The inhibition of HSP90α protected the primary cultures of striatal neurons from METH/HT-induced necroptosis. In conclusion, HSP90α plays an important role in METH/HT-induced neuronal necroptosis and the HSP90α-RIP3 pathway is a promising therapeutic target for METH/HT-induced neurotoxicity in the striatum.

Adenosine A3 receptor activated in H2O2 oxidative stress of primary open-angle glaucoma.

BACKGROUND: Primary open-angle glaucoma (POAG), as one of the leading reasons for blindness, is mainly due to trabecular meshwork (TM) dysfunction. Bioinformatics analysis was used to find related genes involved in TM oxidative stress, which is a major cause of TM fibrosis. METHODS: A total of three datasets from the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs). Gene expression relationships were enriched by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) pathways. The interaction network was listed by the protein-protein interaction (PPI) network. The expression of adenosine A3 receptor (ADORA3) was validated in POAG tissue and human trabecular meshwork cells (HTMCs) by western blot (WB) and reverse transcription polymerase chain reaction (RT-PCR). Additionally, WB and RT-PCR were used to measure oxidative stress injury relative protein and gene expression, respectively, such as fibronectin (FN), collagen-I (Col-I), and α-smooth muscle actin (α-SMA). Cell migration function and vitality were tested via transwell migration assay and Cell Counting Kit-8 (CCK-8). The cell vitality was measured using CCK-8. RESULTS: A total of 61 significant DEGs among the three data sources were analyzed. Among all three different datasets, two significant DEGs [ADORA3 and DNA damage-inducible transcript 4 protein (DDIT4)] were identified. The dataset ADORA3 was selected for further analysis. In the POAG TM tissue, ADORA3 was overexpressed at transcriptional and post-transcriptional levels. Overexpression of ADORA3 reduced TMC viability and migration but upregulated the extracellular matrix (ECM) proteins (FN, Col-I, and α-SMA) expression. It was found that ADORA3 can exacerbate oxidative stress injury in normal TMCs. These results indicated that ADORA3 might play an essential role in the occurrence and progression of POAG. CONCLUSIONS: A total of 61 novel common DEGs identified are related to the development and prognosis of POAG. In the POAG, ADORA3 was verified as overexpressed; therefore, it may be associated with an oxidative stress injury in TMCs.

Guidelines for Regulated Cell Death Assays: A Systematic Summary, A Categorical Comparison, A Prospective.

Over the past few years, the field of regulated cell death continues to expand and novel mechanisms that orchestrate multiple regulated cell death pathways are being unveiled. Meanwhile, researchers are focused on targeting these regulated pathways which are closely associated with various diseases for diagnosis, treatment, and prognosis. However, the complexity of the mechanisms and the difficulties of distinguishing among various regulated types of cell death make it harder to carry out the work and delay its progression. Here, we provide a systematic guideline for the fundamental detection and distinction of the major regulated cell death pathways following morphological, biochemical, and functional perspectives. Moreover, a comprehensive evaluation of different assay methods is critically reviewed, helping researchers to make a reliable selection from among the cell death assays. Also, we highlight the recent events that have demonstrated some novel regulated cell death processes, including newly reported biomarkers (e.g., non-coding RNA, exosomes, and proteins) and detection techniques.

c-FLIP regulates pyroptosis in retinal neurons following oxygen-glucose deprivation/recovery via a GSDMD-mediated pathway.

Cellular FLICE-inhibitory protein (c-FLIP), an anti-apoptotic regulator, shows remarkable similarities to caspase-8, which plays a key role in the cleavage of gasdermin D (GSDMD). It has been reported that the oxygen-glucose deprivation/recovery (OGD/R) model and lipopolysaccharide (LPS)/adenosine triphosphate (ATP) treatment could induce inflammation and pyroptosis. However, the regulatory role of c-FLIP in the pyroptotic death of retinal neurons is unclear. In this study, we hypothesized that c-FLIP might regulate retinal neuronal pyroptosis by GSDMD cleavage. To investigate this hypothesis, we induced retinal neuronal damage in vitro (OGD/R and LPS/ATP) and in vivo (acute high intraocular pressure [aHIOP]). Our results demonstrated that the three injuries triggered the up-regulation of pyroptosis-related proteins, and c-FLIP could cleave GSDMD to generate a functional N-terminal (NT) domain of GSDMD, causing retinal neuronal pyroptosis. In addition, c-FLIP knockdown in vivo ameliorated the already established visual impairment mediated by acute IOP elevation. Taken together, these findings revealed that decreased c-FLIP expression protected against pyroptotic death of retinal neurons possibly by inhibiting GSDMD-NT generation. Therefore, c-FLIP might provide new insights into the pathogenesis of pyroptosis-related diseases and help to elucidate new therapeutic targets and potential treatment strategies.