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Introduction: Gold nanoparticles (AuNPs) have been developed as treatment materials for various diseases and shown magnificent potential. By contrast to the broad toxicological studies on the single exposure (AuNPs), how the other health risks modulate the toxicological profile of AuNPs remains to be investigated. Plastics are among the most common health risks in daily life due to the broad utilization of plastic products. Therefore, in this study, we aimed to reveal the toxicological effects induced by co-exposure of gold nanorod (AuR) and polystyrene micro- and nano-plastics (hereinafter, referred to as AuRmPS and AuRnPS, respectively) in mice. Methods: Systematic biochemical characterizations were performed to investigate the hepatotoxicity, nephrotoxicity, neurotoxicity, inflammatory responses, alterations in gut microbiota induced by co-exposure, and to analyze the toxicological phenomena from the roles of reactive oxygen species and gut-organ axis. Results: It has been found that hepatotoxicity, nephrotoxicity, neurotoxicity, and inflammation were exacerbated in AuRnPS and AuRmPS, and gut microbiota composition was more severely altered in AuRnPS exposure. These results suggest the necessity of reducing plastics exposure in AuNPs-based therapies. Moreover, protection against the nano-sized plastic particles holds higher priority. Conclusion: These findings will facilitate the explorations of methods to reduce therapeutic toxicity and improve biosafety for specific treatments by referring to the orders of importance in protecting different organs.

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A key aspect of preeclampsia pathophysiology is the reduced invasiveness of trophoblasts and the impairment of spiral artery remodelling. Understanding the causes of altered trophoblast function is critical to understand the development of preeclampsia. B7-H4, a checkpoint molecule, controls a wide range of processes, including T-cell activation, cytokine release, and tumour progression. Our previous findings indicated that B7-H4 levels are elevated in both maternal blood and placental villous tissue during the early stages of preeclampsia. Here, we investigated the function of B7-H4 in trophoblast physiology. Recombinant B7-H4 protein was used to treat human SGHPL-5 extravillous trophoblast cells. Biological functions were investigated using MTT, wound healing, and transwell assays. Signalling pathways were analysed by immunoblotting and immunofluorescence. The functionality of B7-H4 was further confirmed by immunoblotting and immunohistochemical analysis in placental tissues from control and preeclamptic patients following therapeutic plasma exchange (TPE) or standard of care treatment. This study showed that B7-H4 inhibited the proliferation, migration, and invasion capacities of SGHPL-5 extravillous cells while promoting apoptosis by downregulating the PI3K/Akt/STAT3 signalling pathway. These results were consistently confirmed in placental tissues from preterm controls compared to early-onset preeclamptic placental tissues from patients treated with standard of care or TPE treatment. B7-H4 may play a role in the development of preeclampsia by inhibiting essential functions of extravillous trophoblast cells during placental development. One possible mechanism by which TPE improves pregnancy outcomes in preeclampsia is through the elimination of B7-H4 amongst other factors.

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Based on previous experiments, we demonstrated puerarin inhibited the proliferation of BC T24 cells. To further explore the molecular mechanisms, whole transcriptome sequencing combined with bioinformatics analysis was performed. The results showed puerarin significantly inhibited T24 proliferation and pathway enrichment analysis of differentially expressed RNAs were mainly enriched in Cell cycle, PI3K/AKT, Ras family chromatin remodeling. lncRNAs and circRNAs may regulate miRNAs, thereby regulating the expression of ITGA1, PAK2 and UTRN. The predicted upstream transcription factor ERG and puerarin were well docked, which may be one of the underlying mechanisms by which puerarin inhibiting BC cells.

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BACKGROUND: Wernicke encephalopathy is a neurological disorder caused by thiamine deficiency, commonly seen in alcoholic populations but also involving other circumstances that may lead to thiamine deficiency. The recognition of Wernicke encephalopathy often depends on clinicians' keen ability to detect its typical triad of features; however, most cases do not present with the full constellation of signs, which complicates the timely identification of Wernicke encephalopathy. CASE SUMMARY: This case report describes a patient with nasopharyngeal carcinoma who developed abnormal ocular function and ataxia following concurrent chemoradiotherapy, without a history of alcohol abuse. With the aid of radiological examinations, he received a timely diagnosis and treatment; however, his symptoms did not fully resolve during follow-up. CONCLUSION: For patients with malignant tumors exhibiting neurological symptoms, clinicians should consider the possibility of Wernicke encephalopathy and provide prophylactic thiamine therapy.

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With the continuous development of identification technologies such as mass spectrometry,omics,and antibody technology,post-translational modification (PTM) has demonstrated increasing potential in medical research.PTM as a novel chemical modification method provides new perspectives for the research on diseases.Succinylation as a novel modification has aroused the interest of more and more researchers.The available studies about succinylation mainly focus on a desuccinylase named sirtuin 5.This enzyme plays a key role in modification and has been preliminarily explored in cardiovascular studies.This paper summarizes the influencing factors and regulatory roles of succinylation and the links between succinylation and other PTMs and reviews the research progress of PTMs in the cardiovascular field,aiming to deepen the understanding about the role of this modification and give new insights to the research in this field.

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With the advancement of RNA sequencing technology, there has been a drive to uncover and elucidate the pivotal role of A-to-I RNA editing events in tumorigenesis. However, A-to-I miRNA editing events have been clearly identified in bladder cancer, the molecular mechanisms underlying their role in bladder cancer remain unclear. In our investigation, we observed a notable under-expression of edited miR-154-p13-5p in bladder cancer (BC) tissues, in contrast to normal counterparts. Remarkably, heightened expression levels of edited miR-154-p13-5p correlated with improved survival outcomes. To assess the impact of modified miR-154-p13-5p, we conducted a string of cell phenotype assays through transfection of the corresponding miRNAs or siRNAs. The results unequivocally demonstrate that edited miR-154-p13-5p exerts a substantial inhibitory influence on proliferation, migration, and induces apoptosis by specifically targeting LIX1L in bladder cancer. Moreover, we observed that the editing of miR-154-p13-5p or LIX1L-siRNAs inhibits the expression of LIX1L, thereby suppressing EMT-related proteins and cell cycle protein CDK2. Simultaneously, an upregulation in the expression levels of Caspase-3 and Cleaved Caspase-3 were also detected. Our research findings suggest that the upregulation of edited miR-154-p13-5p could potentially enhance the prognosis of bladder cancer, thereby presenting molecular biology-based therapeutic strategies.

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The global spread of SARS-CoV-2 has increased infections among pregnant women. This study aimed to explore placental pathology alterations and angiogenic factor levels in term pregnant women after SARS-CoV-2 infection in a retrospective single-center study. Additionally, we investigated the role and underlying mechanism of the vascular inflammation-promoting, cysteine-rich protein 61 (CYR61/CCN1) in this context. All analyses were performed in term pregnant women infected with or without SARS-CoV-2. The sFlt-1, PlGF, and sEng serum levels were quantified using ELISA. Placental protein expressions were examined by immunoblot and immunostaining. Additionally, the effect of CCN1 protein on SGHPL-5 trophoblast cells was examined. We found that SARS-CoV-2 activated the inflammatory response in pregnant women, leading to pronounced vascular alterations in placental villous tissues. Elevated serum anti-angiogenic factors (sFlt-1, sEng) upon SARS-CoV-2 infection may directly contribute to these pathological changes. Upregulated CCN1 and pNF-κB in placental villous tissues of infected patients are identified as crucial factors in placental alterations. As a conclusion, CCN1 was significantly elevated in the placentas of term pregnant women infected with SARS-CoV-2. By activating a cascade of inflammatory responses, CCN1 induced the production of the anti-angiogenic factors sFlt-1 and sEng, which may lead to abnormal placental vascular architecture.

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Compared to SnTe and PbTe base materials, the GeTe matrix exhibits a relatively high Seebeck coefficient and power factor but has garnered significant attention due to its poor thermal transport performance and environmental characteristics. As a typical p-type IV-VI group thermoelectric material, W-doped GeTe material can bring additional enhancement to thermoelectric performance. In this study, the introduction of W, Ge1-xWxTe (x = 0, 0.002, 0.005, 0.007, 0.01, 0.03) resulted in the presence of high-valence state atoms, providing additional charge carriers, thereby elevating the material's power factor to a maximum PFpeak of approximately 43 µW cm-1 K-2, while slightly optimizing the Seebeck coefficient of the solid solution. Moreover, W doping can induce defects and promote slight rhombohedral distortion in the crystal structure of GeTe, further reducing the lattice thermal conductivity κlat to as low as approximately 0.14 W m-1 K-1 (x = 0.002 at 673 K), optimizing it to approximately 85% compared to the GeTe matrix. This led to the formation of a p-type multicomponent composite thermoelectric material with ultra-low thermal conductivity. Ultimately, W doping achieves the comprehensive enhancement of the thermoelectric performance of GeTe base materials, with the peak ZT value of sample Ge0.995W0.005Te reaching approximately 0.99 at 673 K, and the average ZT optimized to 0.76 in the high-temperature range of 573-723 K, representing an increase of approximately 17% compared to pristine GeTe within the same temperature range.

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During the process of peripheral nerve repair, there are many complex pathological and physiological changes, including multi-cellular responses and various signaling molecules, and all these events establish a dynamic microenvironment for axon repair, regeneration, and target tissue/organ reinnervation. The immune system plays an indispensable role in the process of nerve repair and function recovery. An effective immune response not only involves innate-immune and adaptive-immune cells but also consists of chemokines and cytokines released by these immune cells. The elucidation of the orchestrated interplay of immune cells with nerve regeneration and functional restoration is meaningful for the exploration of therapeutic strategies. This review mainly enumerates the general immune cell response to peripheral nerve injury and focuses on their contributions to functional recovery. The tissue engineering-mediated strategies to regulate macrophages and T cells through physical and biochemical factors combined with scaffolds are discussed. The dynamic immune responses during peripheral nerve repair and immune-cell-mediated tissue engineering methods are presented, which provide a new insight and inspiration for immunomodulatory therapies in peripheral nerve regeneration.

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Bisphenol A (BPA) is one of the environmental endocrine disruptors, due to its chemical stability it exists in abundant concentrations in water and soil consequently accumulating in the food chain and causing many endocrine-related health problems. So far, studies on the effects of BPA on marine invertebrates have focused on acute toxicity, endocrine regulation, reproduction, and development. However, fewer studies have been conducted on marine benthos. The current study aimed to detect the accumulation of BPA and its impact on tissue structure, antioxidant capacity, and immune indexes in marine worm, Urechis unicinctus. U. unicinctus, as a common marine benthic animal, were exposed to different concentrations of BPA. Blood cells and intestinal tract were taken for tissue structure inspection, and supernatant of the coelomic fluid was collected for oxidative and antioxidant biomarkers. Results showed that the accumulation of BPA in muscles of U. unicinctus tended to increase with exposure time. BPA induced a rise in H2O2 and MDA content, and altered the activities of CAT, T-SOD, GST, LSZ and ACP, weaken the immune system functions. Moreover, pathological observation showed that BPA caused severe histopathology in the respiratory intestine, stomach, and midgut. These results will be helpful to understand the response mechanism of U. unicinctus under BPA exposure and provide a reference for controlling the aquaculture conditions and marine water quality of U. unicinctus.

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A mild and efficient synthesis of various aryl sulfonyl fluorides from diaryliodonium salts under organophotocatalysis via a radical sulfur dioxide insertion and fluorination strategy is presented. Diaryliodonium salts are used as aryl radical precursors, the 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO) as a sulfonyl source and cheap KHF2 as a desirable fluorine source, respectively. Notably, the electronic properties of substituents on the aromatic rings in diaryliodonium salts have a significant influence on the reaction yields.

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We disclose herein a photocatalytic decarboxylative fluorosulfonylation reaction of various hypervalent iodine(III) carboxylates in combination with 1,4-diazabicyclo[2.2.2]octane-bis(sulfur dioxide) adduct as a sulfonyl source and KHF2 as a desirable fluorine source via a radical sulfur dioxide insertion and fluorination strategy. A one-pot photocatalytic decarboxylative fluorosulfonylation reaction of various carboxylic acids mediated by PhI(OAc)2 was realized, as well. Notably, this transformation can be performed under heating conditions without the need for catalysts.

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BACKGROUND: Bladder urothelial carcinoma (BUC) ranks second in the incidence of urogenital system tumors, and the treatment of BUC needs to be improved. Puerarin, a traditional Chinese medicine (TCM), has been shown to have various effects such as anti-cancer effects, the promotion of angiogenesis, and anti-inflammation. This study investigates the effects of puerarin on BUC and its molecular mechanisms. METHODS: Through GeneChip experiments, we obtained differentially expressed genes (DEGs) and analyzed these DEGs using the Ingenuity® Pathway Analysis (IPA®), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. The Cell Counting Kit 8 (CCK8) assay was used to verify the inhibitory effect of puerarin on the proliferation of BUC T24 cells. String combined with Cytoscape® was used to create the Protein-Protein Interaction (PPI) network, and the MCC algorithm in cytoHubba plugin was used to screen key genes. Gene Set Enrichment Analysis (GSEA®) was used to verify the correlation between key genes and cell proliferation. RESULTS: A total of 1617 DEGs were obtained by GeneChip. Based on the DEGs, the IPA® and pathway enrichment analysis showed they were mainly enriched in cancer cell proliferation and migration. CCK8 experiments proved that puerarin inhibited the proliferation of BUC T24 cells, and its IC50 at 48 hours was 218µmol/L. Through PPI and related algorithms, 7 key genes were obtained: ITGA1, LAMA3, LAMB3, LAMA4, PAK2, DMD, and UTRN. GSEA showed that these key genes were highly correlated with BUC cell proliferation. Survival curves showed that ITGA1 upregulation was associated with poor prognosis of BUC patients. CONCLUSION: Our findings support the potential antitumor activity of puerarin in BUC. To the best of our knowledge, bioinformatics investigation suggests that puerarin demonstrates anticancer mechanisms via the upregulation of ITGA1, LAMA3 and 4, LAMB3, PAK2, DMD, and UTRN, all of which are involved in the proliferation and migration of bladder urothelial cancer cells.

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We developed an efficient palladium-catalyzed fluorosulfonylation reaction of aryl thianthrenium salts to smoothly prepare various aryl sulfonyl fluorides using cheap Na2S2O4 as a convenient sulfonyl source in combination with N-fluorobenzenesulfonimide (NFSI) as an ideal fluorine source under mild reduction conditions. A one-pot synthesis of aryl sulfonyl fluorides starting from various arenes was established as well without the need for separating aryl thianthrenium salts. The practicality of this protocol was demonstrated by gram-scale synthesis, derivatization reactions, and excellent yields.

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To investigate the effects of high hydrostatic pressure (HHP) on the conformation and IgG binding capacity, tropomyosin (TM) from Pacific oysters was subjected to high pressures of 300, 450 or 600 MPa. The results showed that the α-helix of TM with HHP-induced was decreased, while ß-turn, ß-sheet (predominantly) and random coil were increased. The surface hydrophobicity and sulfhydryl group content of TM were increased, while the fluorescence/UV intensity were decreased after HHP treatment. Atomic force microscopy (AFM) result exhibited that the morphology of TM was changed at 600 MPa and formed fibrous structures. The IgG binding capacity of TM and digested TM was markedly reduced when the pressure was increased, especially at 600 MPa. Overall, this study indicated that HHP-induced conformational changes in TM contributed to the reduction in IgG binding capacity. These findings suggested that HHP may be a promising non-thermal technology for producing hypoallergenic oyster products.

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Glioma is the most common and aggressive primary brain tumor in adults with high morbidity and mortality. Rapid proliferation and diffuse migration are the main obstacles to successful glioma treatment. Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L., possesses a significant antitumor role in several malignant tumors. In this study, we report that xanthatin suppressed glioma cells proliferation and induced apoptosis in a time- and concentration-dependent manner, and was accompanied by autophagy inhibition displaying a significantly reduced LC3 punctate fluorescence and LC3II/I ratio, decreased level of Beclin 1, while increased accumulation of p62. Notably, treating glioma cells with xanthatin resulted in obvious activation of the PI3K-Akt-mTOR signaling pathway, as indicated by increased mTOR and Akt phosphorylation, decreased ULK1 phosphorylation, which is important in modulating autophagy. Furthermore, xanthatin-mediated pro-apoptosis in glioma cells was significantly reversed by autophagy inducers (rapamycin or Torin1), or PI3K-mTOR inhibitor NVP-BEZ235. Taken together, these findings indicate that anti-proliferation and pro-apoptosis effects of xanthatin in glioma are most likely by inhibiting autophagy via activation of PI3K-Akt-mTOR pathway, suggesting a potential therapeutic strategy against glioma.

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The binding of programmed death-1 (PD-1) on the surface of T cells and PD-1 ligand 1 (PD-L1) on tumor cells can prevent the immune-killing effect of T cells on tumor cells and promote the immune escape of tumor cells. Therefore, immune checkpoint blockade targeting PD-1/PD-L1 is a reliable tumor therapy with remarkable efficacy. However, the main challenges of this therapy are low response rate and acquired resistance, so that the outcomes of this therapy are usually unsatisfactory. This review begins with the description of biological structure of the PD-1/PD-L1 immune checkpoint and its role in a variety of cells. Subsequently, the therapeutic effects of immune checkpoint blockers (PD-1 / PD-L1 inhibitors) in various tumors were introduced and analyzed, and the reasons affecting the function of PD-1/PD-L1 were systematically analyzed. Then, we focused on analyzing, sorting out and introducing the possible underlying mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade including abnormal expression of PD-1/PD-L1 and some factors, immune-related pathways, tumor immune microenvironment, and T cell dysfunction and others. Finally, promising therapeutic strategies to sensitize the resistant patients with PD-1/PD-L1 blockade treatment were described. This review is aimed at providing guidance for the treatment of various tumors, and highlighting the drug resistance mechanisms to offer directions for future tumor treatment and improvement of patient prognosis.

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OBJECTIVE: To study the effect and safety of microscopic varicocele cluster ligation (MVCL). METHODS: We selected 28 patients undergoing bilateral microscopic spermatic vein ligation in Xuzhou Central Hospital from July 2021 to June 2022. Using the computerized randomization method, we performed MVCL or microscopic varicocele ligation (MVL) for the right or the left spermatic cord, respectively. We recorded the operation time, intraoperative blood loss, the numbers of the spermatic veins ligated and the arteries and lymphatic vessels preserved in each surgical side. A surgeon unaware of the surgical approach on the operative side collected the Visual Analogue Scale (VAS) pain scores, nodular foreign body sensation, relief of scrotal cramps, complications, and long-term recurrence from the patients. RESULTS: Compared with the MVL group, the MVCL group showed significantly shorter time for spermatic vein ligation (ï¼»56.21±13.96ï¼½ vs ï¼»31.43±10.13ï¼½ min, P<0.01), lower VAS scores on the 1st postoperative day (P <0.05) and a lower incidence of intra-scrotal nodular foreign body sensation in the 1st postoperative month (P <0.05). There were no statistically significant differences in the intraoperative blood loss, numbers of spermatic veins ligated and arteries and lymphatic vessels preserved, VAS scores at 3 and 7 postoperative days, incidence of complications and long-term recurrence between the two groups (P >0.05). CONCLUSION: MVCL is superior to MVL in reducing the time of spermatic vein ligation and improving the efficiency, efficacy and safety of the procedure, and therefore worthy of clinical promotion.

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Protein phosphorylation is an important post-transcriptional modification involving an extremely wide range of intracellular signaling transduction pathways, making it an important therapeutic target for disease intervention. At present, numerous drugs targeting protein phosphorylation have been developed for the treatment of various diseases including malignant tumors, neurological diseases, infectious diseases, and immune diseases. In this review article, we analyzed 303 small-molecule protein phosphorylation kinase inhibitors (PKIs) registered and participated in clinical research obtained in a database named Protein Kinase Inhibitor Database (PKIDB), including 68 drugs approved by the Food and Drug Administration of the United States. Based on previous classifications of kinases, we divided these human protein phosphorylation kinases into eight groups and nearly 50 families, and delineated their main regulatory pathways, upstream and downstream targets. These groups include: protein kinase A, G, and C (AGC) and receptor guanylate cyclase (RGC) group, calmodulin-dependent protein kinase (CaMK) group, CMGC [Cyclin-dependent kinases (CDKs), Mitogen-activated protein kinases (MAPKs), Glycogen synthase kinases (GSKs), and Cdc2-like kinases (CLKs)] group, sterile (STE)-MAPKs group, tyrosine kinases (TK) group, tyrosine kinase-like (TKL) group, atypical group, and other groups. Different groups and families of inhibitors stimulate or inhibit others, forming an intricate molecular signaling regulatory network. This review takes newly developed new PKIs as breakthrough point, aiming to clarify the regulatory network and relationship of each pathway, as well as their roles in disease intervention, and provide a direction for future drug development.

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Herein, we studied the increasing tendency of photoacoustic (PA) conversion efficiency of the Au/polydimethylsiloxane (PDMS) composite. The thickness of the Au layer was optimized by modeling the PA process based on the Drude-Lorentz model and finite element analysis method, and corresponding results were verified. The results showed that the optimal Au thickness of the Au/PDMS composite was 35 nm. Finally, the Au/PDMS composites were coated onto the surface of aluminum alloys, which improved the thermoelastic laser ultrasonic (LU) signals to near 100 times. Besides, the defect mapping was performed by thermoelastic LU signals with Au/PDMS coating and ablation LU signals without coating; the Pearson correlation coefficient was higher than 0.95. The application in the defect detection in metal could provide guides for nondestructive detection on metals by laser ultrasound.