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Objective: In this study, two human hepatocellular carcinoma cell lines, HepG2 (p53+/+) and Hep3B (p53-/-), were used with different p53 mutation statuses. The role of p53 in the induction of cytotoxicity by H2Valdien derivatives was investigated, as well as how p53 regulates GADD45a and p21. To examine whether the mechanism of action of H2Valdien derivatives on cell cycle arrest and apoptosis in human hepatocellular carcinoma cells is related to p53 deficiency. Methods: Cell viability was analyzed using the CCK-8 assay, and RNA sequencing was used for differential gene expression and enrichment analyses. The expression of apoptosis and cell cycle related proteins was analyzed by western blotting. DAPI and TUNEL staining techniques were employed to effectively visualize the nuclear morphology and apoptotic properties of the cells under investigation. Cell proliferation ability was assessed using colony formation assays, and mitochondrial membrane potential (MMP) was detected by JC-1 staining. Cell cycle progression was assessed by flow cytometry. Results: H2Valdien derivatives (5, 10, 20, and 40 mg/L) inhibited the proliferation of HepG2 and Hep3B cells and the formation of cell colonies in a dose-dependent manner, and decreased the MMP of HepG2 cells, but had no effect on the MMP of Hep3B cells. H2Valdien derivatives upregulated cleaved caspase-9, cleaved PARP, and Bax in HepG2 cells but not in Hep3B cells. RNA sequencing analysis revealed that H2Valdien derivatives increased p53, p21, and GADD45A expression, and western blotting and flow cytometry confirmed this finding. Despite the induction of p21 and GADD45a in Hep3B cells, there was no change in related proteins associated with drug concentration. Conclusion: GADD45a and p21 expression is regulated by H2Valdien derivatives in a p53-dependent manner, and p53 has a pro-apoptotic impact on H2Valdien derivative-induced toxicity. H2Valdien derivative-induced apoptosis and cycle hinder are reduced by p53 deletion.

This work synthesized CuS–Au heterojunction by galvanic substitution method. The synthesis method is green and simple. CuS NPs exhibit remarkable oxidase-like activity. The immunosensor prepared under the optimized conditions has excellent analytical performance.

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.

We aimed to identify the risk factors for subsequent carbapenem-resistant Enterobacterales (CRE) infections in patients with initial rectal colonization with CRE.We conducted a retrospective case-control study on inpatients with rectal CRE colonization between January 2019 and December 2020. Clinical and microbiological data were extracted from hospital patients' medical records and the clinical microbiology laboratory. Risk factors were assessed and compared between patients with CRE colonization who had subsequent infections and those who did not have infections.Among 1064 patients screened for CRE, we enrolled 205 patients with rectal CRE colonization. Among the 205 colonized bacteria, 78.5% were Klebsiella pneumoniae, with 62.9% of them producing Klebsiella pneumoniae carbapenemase (KPC). Multivariate logistic regression analysis revealed that more than three times hospitalization (p = 0.026), being in a coma (p = 0.019), and exposure to carbapenems (p = 0.015) were independent risk factors for CRE clinical infection among CRE rectal carriers.This is the first study to report that more than three times hospitalization is an independent risk factor for subsequent CRE clinical infection in CRE intestinal carriers. Carbapenem-resistant Klebsiella pneumoniae is the most important species isolated from hospitalized CRE rectal carriers and is the most common cause of subsequent infections.

Colorectal cancer is the third most common malignant tumor and a leading cause of cancer death. Currently lacks effective therapies available to improve the prognosis. In the present study, VALD-3, an important Schiff base ligand from o-vanillin derivatives was evaluated for its anti-cancer activity in vitro and in vivo against colorectal cancer. The effect of VALD-3 on colorectal cancer cells proliferation was assessed using MTT assay and the cell migration was evaluated using wound healing scratch assay. The appearance of apoptotic colorectal cancer cells was detected by flowcytometry analysis. Morphological changes caused by VALD-3 induced apoptosis were also observed by Hoechst 33258 staining. The flow cytometry assay was also used to measure cell cycle arrest. The expression levels of TP53 and Bad were analyzed using quantitative real-time PCR. Protein expression of P53, Wnt/β-catenin signaling pathway proteins, apoptosis proteins and cell cycle-related protein were viewed by Western blotting. In addition, HT-29 cells xenograft tumor model was used for the study in vivo. Immunohistochemistry (IHC) staining was employed to detect the P53 protein expression. The results showed that VALD-3 obviously inhibited the proliferation and migration for colorectal cancer cells. In addition, flow cytometry analysis demonstrated that VALD-3 markedly increased early and late apoptosis on colorectal cancer cells, respectively. VALD-3 induced cell cycle arrest at the G0/G1 phase. Most importantly, tumor growth in HT-29 xenograft mice was suppressed by VALD-3, but no significant change in body weight. As confirmed by IHC staining from tumor tissue, the P53 proteins expression increased. These results suggested that VALD-3 represses cell proliferation and induces apoptosis associated with upregulating tumor suppressor activity of p53 to inhibit Wnt/β-catenin signal pathway, and it is a potential anticancer agent for colorectal cancer.

Hyperuricemia contributes to chronic kidney disease development. However, it has been historically viewed with limited research interest. In this study, we mimicked the development of hyperuricemic nephropathy by using a potassium oxonate-induced hyperuricemia rat model. We found that administering vitamin C at 10 mg/kg/day effectively ameliorated hyperuricemic nephropathy. Compared to the control group, rats with hyperuricemia had significantly increased serum uric acid level, xanthine oxidase activity, and urine microalbumin level, by 5-fold, 1.5-fold, and 4-fold, respectively. At the same time, vitamin C supplementation reverted these values by 20% for serum uric acid level and xanthine oxidase activity and 50% for microalbumin level. Vitamin C also alleviated renal pathology and decreased the expression of pro-inflammatory and pro-fibrotic markers. A further mechanistic study suggested that vitamin C might attenuate hyperuricemic nephropathy in renal tubular epithelial cells induced by monosodium urate (MSU) crystal, at least in part, by directly inhibiting IL-6/JAK2/STAT3 signaling pathway. Meanwhile, in macrophages, vitamin C inhibited the expression of TGF-β, and reduced ROS level induced by MSU by about 35%. In short, our results suggest that vitamin C supplementation delay the progression of hyperuricemic nephropathy.

The internal structure analysis of radial tires is of great significance to improve vehicle safety and during tire research. In order to perform the digital analysis and detection of the internal composition in radial tire cross-sections, a detection method based on digital image processing was proposed. The research was carried out as follows: (a) the distribution detection and parametric analysis of the bead wire, steel belt, and carcass in the tire section were performed by means of digital image processing, connected domain extraction, and Hough transform; (b) using the angle of location distribution and area relationship, the detection data were optimized through coordinate and quantity relationship constraints; (c) a detection system for tire cross-section components was designed using the MATLAB platform. Our experimental results showed that this method displayed a good detection performance, and important practical significance for the research and manufacture of tires.

A method for detecting of Carcinoembryonic antigen(CEA) with improved accuracy is urgently needed. In this work, a dual-mode immunosensor for accurate detection of CEA was fabricated, which used a Cu-doped Mo

The recovery of heavy metals from electroplating sludge is important for alleviating heavy metal pollution and recycling metal resources. However, the selective recovery of metal resources is limited by the complexity of electroplating sludge. Herein, CuFe bimetallic Fenton-like catalysts were successfully prepared from electroplating sludge by a facile room-temperature ultrasonic-assisted co-precipitation method. The prepared CuFe-S mainly consisted of nanorods with diameters of 20-30 nm and lengths of 100-200 nm and a small number of irregular particles. Subsequently, we performed tetracycline (TC) degradation experiments, and the results showed that the product CuFe-S had very good performance over a wide pH range (2-11). At an initial pH = 2, CuFe-S could degrade 91.9% of 50 mg L

yroptosis, an inflammatory form of Programmed cell death (PCD) and so far, the function of Schiff base compounds in pyroptosis cell death has not been reported. Here, we show that VALD3, a Ligand derivative of Schiff base, treated Triple negative breast cancer (TNBC) cells exhibited specific pyroptotic characteristics, including cell swelling, balloon-like bubbling and inflammatory cytokine release through pore formation in the plasma membrane, eventually suppressing the tumor growth of TNBC. In addition, Western blot analysis revealed that the cleavage of Gasdermin E (GSDME),was related to the activation of caspase-3 in TNBC cells treated by VALD3. Consistent with this, treatment with zDEVD-FMK,a caspase-3 specific inhibitor,reduces VALD3-induced GSDME–N-terminal fragment cleavage and pyroptosis. Mechanistically, VALD3 elevated the level of reactive oxygen species(ROS)and c-Jun NH2-terminal kinase (JNK)phosphorylation.NAC,a ROS scavenger,reversed the pyroptosis and JNK phosphorylation in MDA-MB-468 and MDA-MB-231 treated by VALD3. Activated JNK recruited Bax to mitochondria to form a heterodimer with Bcl-2, which stimulated the release of cytochrome c into the cytoplasm, followed by caspase-3 activation and GSDME-depended pyroptosis in TNBC cells. Therefore, in TNBC cells,VALD-3 treatment induces the ROS/JNK/Bax-mitochondrial apoptosis pathway. Thereby activating Caspase-3 and inducing cleavage of GSDME to execute pyroptosis. These findings bring an unexpected concept that GSDME-dependent pyroptosis is an unrecognized mechanism by which VALD3 eradicates neoplastic cells, and provide new insights into the clinical application of anticancer therapeutics.

Hongling Li, Mao Zhou, Xia Chen, Yawen Zhang, Zijuan Jian, Qun Yan, Wen-En Liu Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Wen-En LiuDepartment of Clinical Laboratory, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, People’s Republic of ChinaTel +86-731-84327440Fax +86-731-84327332Email wenenliu@163.comPurpose: Carbapenem-resistant Enterobacteriaceae (CRE) strains are extensively resistant to most antibiotics. Tigecycline is one of the few effective drugs that can be used to treat infections caused by CRE. The aim of this study was to evaluate the accuracy of different methods for detecting the susceptibility of CRE to tigecycline.Methods: Seven commonly used drug susceptibility testing methods were compared and evaluated for the ability to determine CRE tigecycline susceptibility: broth microdilution (BMD), agar dilution method (ADM), disk diffusion method, Etest, MicroScan, Vitek2 COMPACT, and BD Phoenix 100.Results: The minimum inhibitory concentration (MIC) of tigecycline to inhibit 50% and 90% of CRE growth (MIC50 and MIC90, respectively) assessed by ADM and BD Phoenix 100 was the same as that determined by the reference method, BMD. The MIC50 was 2 μg/mL, and the MIC90 was 4 μg/mL. The highest number of susceptible strains was detected by MicroScan, followed by BMD, Etest, ADM, BD Phoenix 100, Vitek2 COMPACT, and disk diffusion method, in descending order. No significant differences were observed among the tigecycline susceptibility results (P > 0.05) obtained from MicroScan, Etest, BD Phoenix 100, and BMD. BMD confirmed that 82.0% of strains were susceptible to tigecycline. ADM, MicroScan, and BD Phoenix 100 yielded the categorical agreement of 96%, 92%, and 93%, respectively. No method was found to present any very major errors (VMEs), and only the Vitek2 COMPACT yielded major errors (MEs) greater than 3%.Conclusion: Among the seven methods tested, the ADM, MicroScan, and BD Phoenix 100 methods were accurate for determining the tigecycline susceptibility of CRE. MicroScan was acceptable with better performance than other methods.Keywords: tigecycline, antibiotic susceptibility test, carbapenem-resistant Enterobacteriaceae, CRE

As part of the search for new steroid substances with potential application in oncology, a series of endoperoxide steroid derivatives (7a-n) containing a thiazole system were synthesized and evaluated for their cytotoxicities in four tumor cell lines. Among them, compound 7h exhibited the most significant cytotoxic activity against HepG2 cells (IC50 = 4.54 μM), being more potent than ergosterol peroxide. Furthermore, 7h was able to promote apoptosis in HepG2 cells and decrease the mitochondrial membrane potential, accompanied by activating the expression of cytochrome c, caspase-9, caspase-3, and Bax, while Bcl-2 expression was suppressed. The molecular mechanism may refer to the mitochondrial apoptotic pathway. On the whole, the above results incentivize the further study of 7h derivatives as potent anticancer agents.

The antitumor activities of natural paclitaxel (PTX), semisynthetic docetaxel, and cabazitaxel are highly dependent on their C-13 side chains. Therefore, using natural ergosterol peroxide (EP, 1) as the lead compound, two EP-PTX hybrids (EP-A2 and EP-B2) were prepared and their antitumor activities were evaluated against 4 kinds of human MCF-7, HepG2, HCT-116, and A549 cell lines in vitro. The results showed that both EP-A2 and EP-B2 inhibited the growth of all four kinds of tested tumor cell lines. For paclitaxel-resistant MCF-7 cells, both EP-A2 and EP-B2 showed significant inhibitory activity with relatively low IC50 values (9.39 μM and 8.60 μM, respectively). In addition, EP-B2 inhibited the growth of the HepG2 cells (IC50 = 7.82 μM) more successfully than EP. Preliminary studies of the mechanism suggest that EP-B2 could arrest the G1 phase transition in HepG2 cells. In addition, EP-B2 showed an obvious apoptosis-inducing effect in HepG2 cells, as detected by the Annexin V/PI binding assay and the Western blot assay. Hybrid EP-B2 has the potential to become a novel antitumor drug through further study of the mechanism of action and its structural modifications.

Invasive candidiasis is a major threat to human health, and Candida albicans is the most common pathogenic species responsible for this condition. The incidence of drug-resistant strains of C. albicans is rising, necessitating the development of new antifungal drugs. Antimicrobial peptides (AMPs) have recently attracted attention due to their unique ability to evade the drug resistance of microorganisms. However, the mechanism of their activity has not yet been identified. The current study analyzed the mode of action of MAF-1A by confocal microscopy, scanning electron microscopy, fluorescent staining, flow cytometry, and qRT-PCR. The results indicate that MAF-1A disrupts the cell membrane of C. albicans and enters the cell where it binds and interacts with nucleic acids. qRT-PCR demonstrated that the expression of several sterol biosynthesis–related genes in C. albicans was increased after MAF-1A treatment. Together, these findings suggest that MAF-1A exerts antifungal action by affecting both the cell membrane and intracellular components. The antifungal mechanism of MAF-1A is unique, and its identification has great research and clinical significance.

Summary Physical unclonable function (PUF) is a cornerstone of anticounterfeiting. However, conventional PUF key-based secure tags encounter several bottlenecks, such as complicated manufacturing, specialized and tedious readout, long authentication time, and insufficient stability. Here, we utilize various two-dimensional materials (2DMs), including Ti3C2Tx MXene and graphene oxide, to construct multigenerational microstructures as PUF patterns. Two intermediate treatments, cation intercalation and moisture-induced lubrication, are introduced in between sequential contractions to engineer the multiscale patterns in a transfer-free and scalable fashion. A deep learning (DL)-facilitated software is developed to pre-categorize the hierarchical topographies with classifiable features. Thereafter, the search-and-compare is conducted within a smaller database to shorten the overall authentication time. The synergy between 2DM tags and DL-facilitated software enables a reliable and environmentally stable anticounterfeiting technology, DeepKey, showing superior encoding capacity (>10144,494) and short authentication time (∼3.5 min). Our 2DM anticounterfeiting tag is finally integrated with QR codes to provide two-layer information security.

To accomplish ultra-sensitive detection of alpha-fetoprotein(AFP), a novel electrochemical immunosensor using polydopamine-coated Fe

Non-small cell lung cancer (NSCLC) is one of the most malignant epithelial tumors. Studies have suggested that DNA hypermethylation of promoters and abnormal histone modifications could induce tumor suppressor genes (TSGs) downregulation in NSCLC. However, the exact mechanism of TSGs downregulation remains unclear. In this study, we found that there is no difference in the regions of most TSGs promoters in NSCLC. Moreover, we found that there is no DNA methylation difference in the region of VILL promoter in NSCLC compared with adjacent tissue samples by pyrosequencing. We further demonstrated that VILL was markedly reactivated in A549 and H1703 cells infected with miR-26A1 lentivirus while this activation was inhibited by JQ1, an enhancer inhibitor. In addition, we identified that miR-26A1 could function as a tumor suppressor to inhibit proliferation and metastasis of NSCLC cells. Chromatin immunoprecipitation assays revealed that overexpression of miR-26A1 could significantly induce the enrichment of H3K27ac at the enhancer regions in A549 cells. To sum up, our findings revealed that enhancer-mediated TSGs regulation occured in NSCLC, suggesting that miR-26A1 could serve as a key regulator and may be a potential therapeutic target for NSCLC.

Exploring biomarkers for easy and reliable diagnosis of periprosthetic joint infection (PJI) has attracted an increasing attention. Coagulation parameters have been found to be associated with infections, but their role in diagnosing PJI is not well understood. The aim of this study was to explore the diagnostic value of coagulation parameters in PJI.We retrospectively recruited patients who underwent revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) from January 2014 to December 2020. Patients were grouped into PJIs or non-PJIs, and PJIs were further divided into culture positive and culture negative groups. The diagnostic value of coagulation parameters including fibrin degradation product (FDP), D-dimer, platelet count (PC), and platelet count to mean platelet volume ratio (PVR) was evaluated by using receiver operating characteristic curve, in comparison with traditional biomarkers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).A total of 186 patients including 136 THA and 50 TKA were studied. There were 105 PJI and 81 non-PJI patients. The coagulation parameters showed an inferior performance to CRP and ESR, with the area under the curve (AUC) of FDP, D-dimer, PC, PVR, CRP, and ESR being 0.805, 0.571, 0.703, 0.704, 0.882, and 0.824, respectively. The diagnostic performance of those coagulation parameters was similar in THA and TKA PJIs and was not superior to ESR or CRP in either culture-positive or culture-negative PJIs.Coagulation parameters FDP, D-dimer, PC, and PVR are of limited value for the diagnosis of periprosthetic joint infection in both THA and TKA patients.

Antibiotics rank as the most powerful weapons against bacterial infection, but their use is often limited by antibiotic-associated diarrhoea (AAD). Here, we reported that glutamine deficiency might act as a new link between clindamycin-induced dysbiosis and intestinal barrier dysfunction during AAD progression. Using a mouse model, we demonstrated that glutamine became a conditionally essential amino acid upon persistent therapeutic-dose clindamycin exposure, evidenced by a dramatic decrease in intestinal glutamine level and glutaminase expression. Mechanistically, clindamycin substantially confounded the abundance of butyrate-producing strains, leading to the deficiency of faecal butyrate which is normally a fundamental fuel for enterocytes, and in turn increased the compensatory use of glutamine. In addition to its pivotal roles in colonic epithelial cell turnover, glutamine was required for nitric oxide production in classic macrophage-driven host defence facilitating pathogen removal. Importantly, oral administration of glutamine effectively attenuated clindamycin-induced dysbiosis and restored intestinal barrier dysfunction in mice. Collectively, the present study highlighted the importance of gut microbiota in host energy homoeostasis and provided a rationale for introducing glutamine supplementation to patients receiving long-term antibiotic treatment.

Objective. To evaluate the prevalence rate and survival situation of bone metastases in initial nasopharyngeal carcinoma (NPC) patients and the hazard and forecast elements of bone metastases NPC patients. Patients and Methods. The data collected from Surveillance, Epidemiology, and End Results (SEER) program between 2010 and 2016 were evaluated. Univariate and multivariable logistic analysis and the Cox regression were carried out to estimate predictors and elements of the being of bone metastases at diagnosis, respectively. The overall survival of different subgroups were appraised by log-rank tests and the Kaplan–Meier analysis. Results. Factors including male sex, higher N stage, presence of liver, and brain or lung metastases were largely related to the occurrence of bone metastases. The median survival time for bone metastasis NPC patients was 14.0 months. A factor of more than one primary sequence number predicted worse survival. Conclusion. The data offer corresponding risks and prognostic indicators of bone metastases for NPC patients.

Layered MoTe2 has shown great promises for optoelectronics and energy-storage applications due to its exceptional optical and electrochemical properties. To date, considerable efforts have been devoted to fabricating layered MoTe2 with lateral orientation by means of mechanical/chemical exfoliation and chemical vapor deposition (CVD) methods. As compared to its horizontal counterparts, vertically aligned MoTe2 with higher density of active edge sites is expected to possess unique optoelectronic and electrochemical properties, while which has not been reported yet. In this work, we report a versatile and scalable CVD growth of vertically aligned MoTe2 with length of up to ∼ 7.5 µm on Mo foil. Remarkably, the dominant phase of the vertically aligned MoTe2 can be tuned from 2H to 1T’ by increasing the growth temperature from 630 to 780 °C. Owing to the weak interaction between the as-grown MoTe2 and Mo foil, the as-grown MoTe2 can be easily detached from the Mo foil. This in turn enabled economic reuse of the Mo foil for multiple growth. Moreover, the vertical growth of the MoTe2 is proposed to be caused by the internal strain generated during tellurization of Mo foil. Furthermore, the as-grown MoTe2 can also be directly dispersed in solvent to produce high-quality MoTe2 nanosheets. The versatility of this growth strategy was further demonstrated by fabricating other vertically aligned TMDs such as TaTe2 and MoSe2. Hence, this work paves the path towards achieving unique TMDs structures to enable high-performance optoelectronic and electrochemical devices.

Long noncoding RNAs (lncRNAs) have been implicated in a range of developmental processes and diseases, but the roles and mechanisms by which they act in adipogenic differentiation and adipose tissue biology are still unknown. By comparing the different expression patterns of lncRNAs before and after the adipocyte differentiation of human adipose-derived mesenchymal stem cells (hADSCs), we characterized a novel lncRNA, AC092834.1, which is significantly increased in preadipocytes. By gain- and loss-of-function experiments, we demonstrated that lncRNA AC092834.1 potentiated adipogenic differentiation through directly increasing the level of expression of DKK1, which competitively binds with LRP5 to inhibit the Wnt-β-catenin pathway and reduce the inhibition of adipogenesis by Wnt signaling. This finding provides novel mechanistic insights into a critical role for lncRNA AC092834.1 as a regulator of adipogenic differentiation, which expands our knowledge about the molecular mechanisms of obesity and other adipogenic differentiation-related disorders.

Transcription factors have already been proposed to work on some human diseases. Yet the role of translationally controlled tumor protein (TCTP) in cerebral palsy (CP) remains elusive. This study intends to examine the mechanism of TCTP on CP by regulating microRNA-200a (miR-200a).CP models of rats were established referring to the internationally recognized improved hypoxic ischemic encephalopathy modeling method. The neuroethology of rats, ultrastructure and pathological condition in brain tissues of rats were observed through several assays. The expression of TCTP, miR-200a, myelin transcription factor 1-like (Myt1L), tyrosine hydroxylase (TH) and inducible nitric oxide synthase (iNOS) along with apoptosis in brain tissues of rats was detected. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in brain tissues of rats were determined. The binding site between miR-200a and Myt1L was analyzed.TCTP and Myt1L were overexpressed and miR-200a was under-expressed in CP rats. Elevated miR-200a ameliorated neurobehavior of CP rats and pathological injury in brain tissues. Elevated miR-200a up-regulated TH, GSH, GSH-Px, and SOD levels, down-regulated iNOS, ROS, MDA, TNF-α, and IL-6 levels, and attenuated neuronal apoptosis in brain tissues of CP rats. Myt1L was a target gene of miR-200a.Altogether, our study suggested that diminution of transcription factor TCTP up-regulates miR-200a to limit Myt1L expression, thereby improving neurobehavior and oxidative stress injury in CP rats.

Nowadays, immune diseases are a large burden in healthcare. Mesenchymal stem cells (MSCs) have prominent ability in immunomodulation and have been applicated on treating many immune-related diseases. However, the clinical outcomes can be disparate and sometimes completely counterproductive beyond explanation of cell heterogeneity. The theory of immunomodulation plasticity in MSCs has then emerged to explain that MSCs can be induced into proinflammatory MSC1 or anti-inflammatory MSC2 responding to different immune environment. It would be safer and more efficient if we could induce MSCs into a certain immune phenotype, in most cases MSC2, prior to medical treatment. In this study, we screened and identified a classical FDA-approved drug, chlorzoxazone (CZ). Unlike traditional method induced by IFN-γ, CZ can induce MSC into MSC2 phenotype and enhance the immunosuppressive capacity without elevation of immunogenicity of MSCs. CZ-treated MSCs can better inhibit T cells activation and proliferation, promote expression of IDO and other immune mediators in vitro, and alleviate inflammatory infiltration and tissue damage in acute kidney injury rat model more effectively. Moreover, we discovered that CZ modulates phosphorylation of transcriptional factor forkhead box O3 (FOXO3) independent of classical AKT or ERK signaling pathways, to promote expression of downstream immune-related genes, therefore contributing to augmentation of MSCs immunosuppressive capacity. Our study established a novel and effective approach to induce MSC2, which is ready for clinical application.

Practical implementation of porous carbon-based composite phase-change materials (CPCMs) for heat dissipation in high-power-density electronics is usually limited by liquid leakage issues and unsatisfactory thermal conductivity resulting from their relatively low filler fraction and/or existence of interfacial thermal resistance between fillers. Therefore, development of shape-stable CPCMs with high thermal conductivity and large latent heat to avoid overheating of electronics remains challenging. Herein, graphene foams (GFs) with very high densities of up to 204 mg/cm3have been synthesized to act as interconnected porous networks of CPCMs. Notably, the obtained CPCM with a filler loading of 11.1 wt % preserves a high heat capacity (171.8 J/g) with a retention of 84.8% while showing a 22.6-fold enhancement in the thermal conductivity as compared to pure PCM (10.13 vs 0.43 W/m·K). A higher thermal conductivity of 14.29 W/m·K can be achieved by further increasing the filler loading to 17.7 wt %, which outperforms many of the previously reported CPCMs based on the interconnected porous carbon-based frameworks. Owing to the superior interconnected network structure of the dense GFs and the strong interconnection between them and PCM molecules, these CPCMs also exhibit leakage-proof shape stability and excellent thermal reliability (at least 100 cycles). Moreover, a state-of-the-art aluminum (Al) package based on the CPCM (filler loading: 11.1 wt %) possessing weight 60% less than its pure Al panel counterpart has been demonstrated to verify better heat transfer efficiency and more efficient phonon pathways of the CPCM composite than those of the pure PCM, which holds great promise for advanced thermal management of emerging applications in electronics. The authors would like to acknowledge the financial support from Thales.

An ultra-sensitive electrochemical immunosensor for detecting carcinoembryonic antigen was prepared. Graphene oxide-gold was used as the substrate modifier of the sandwich immunosensor. The high conductivity of graphene oxide effectively enhanced the electron transfer rate. The large specific surface area of graphene and the biocompatibility of gold nanoparticles increased the number of primary antibodies. The bovine serum albumin coated silver ��� platinum composite was used as a secondary antibody tag to prepare signal probes. The excellent biocompatibility of bovine serum albumin increased the number of secondary antibody connections. Silver nanoparticles increased the speed of electron transfer, and platinum further enhanced electrochemical sensing capabilities by catalyzing hydrogen peroxide. The immunosensor showed good performance for detecting carcinoembryonic antigen. Under the optimal conditions, the dynamic response range for carcinoembryonic antigen was from 0.005 ng��mL���1 to 100 ng��mL���1 with a detection limit of 0.76 pg��mL���1. The immunosensor also shown high selectivity, suitable stability, and good reproducibility, which provides new capabilities for clinical carcinoembryonic antigen detection.

Objective: To investigate the effect of transcranial direct current stimulation (tDCS) combined with hyperbaric oxygen therapy (HBOT) in patients with delayed encephalopathy after carbon monoxide poisoning (DEACMP).Design: A parallel-group, open-label randomised controlled study.Setting: Hyperbaric Oxygen Therapy Room of the Second Hospital of Hebei Medical University.Subjects: A total of 40 patients were recruited for the current study. Patients were randomly divided into a treatment group and a control group (20 cases/group).Interventions: Control group: conventional, individualised rehabilitation therapy. Treatment group: conventional, individualised rehabilitation therapy and tDCS.Main Measures: cognitive function of patients, the Barthel Index (BI).Results: After treatment, significantly higher MMSE and BI scores, as well as a greater reduction in P300 latency and an increase in P300 amplitude, were observed in the treatment group compared to the control group (MMSE: 13 ± 7 vs. 9 ± 5; P300 latency: 342 ± 29 vs. 363 ± 17 ms; P300 amplitude: 7.0 ± 3.3 vs. 5.1 ± 2.7 μV; all P < 0.05). In both groups, however, MMSE and BI scores, in addition to P300 amplitude, were significantly improved; in contrast, there was a decrease in P300 latency in both groups after treatment compared to before treatment (all P < 0.05).Conclusion: Combined with HBOT, tDCS can help improve cognitive function and ADL in patients with DEACMP. This combination therapy might be a helpful method to enhance the recovery of patients with DEACMP.

A series of novel ergosterol peroxide derivatives with acrylate or propionate side chain were synthesized. All compounds 3a-n were evaluated for their cytotoxicity against four kinds of human carcinoma cell lines (HepG2, MCF-7, HCT-116, and A549). Most of the derivatives displayed stronger cytotoxicity than ergosterol peroxide parent. Among them, compound 3h with the highest potency against HepG2 cell line (IC50 = 2.70 μM), which was 7.47-fold more efficacious than ergosterol peroxide. The results suggested that the introduction of acrylate or propionate side chain at C-3 position of ergosterol peroxide is beneficial to enhance its cytotoxic activity. Compound 3h has potential to become a novel anti-tumor agent through further structural modification.

In this study, we used inexpensive and synthetically simple electrocatalysts as replacements for conventional precious metal materials to reduce hydrogen peroxide (H2O2). We for the first time developed N-doped graphene-coated CuFe@MoC using one-step calcination of binary Prussian blue analogues (PBAs) with Mo6+ cationic grafting precursors. The synergistic interaction of CuFe PBA and MoC increased the catalytically active sites for H2O2 reduction. The catalyst was optimized in terms of the ratio of CuFe PBA to Mo6+, PVP content, and calcination temperature to improve its catalytic activity. When it was used to construct an electrochemical immunosensor for carcinoembryonic antigen (CEA) detection, polydopamine (CuFe-MoC@NG@PDA) was coated on its outer surface to increase the antibody loading and MoS2–Au NPs were used as substrates to improve Ab1 immobilization and accelerate electron transfer at the electrode interface, thereby improving the response signal of the immunosensor. Its concentration was linearly related to the response signal from 10 fg mL−1 to 80 ng mL−1, and the lowest limit of detection was 3 fg mL−1. In addition, the immunosensor has acceptable selectivity and high stability. All data indicate that nanocomposites have electrocatalytic applications.

International audience; Phase Change Material (PCM) have been widely used for thermal energy storage due to their high latent heat of fusion. Several types of PCM are available and can be selected to meet the required melting temperature and latent heat value. However their low thermal conductivity drastically reduces their performances. Without thermal conductivity enhancement, melting would mainly occur at the interface between the heated surface and the PCM, and would slowly spread in the bulk of the PCM. In that sens the use of fillers is necessary. We present here a study on the use of metallic lattice structure as PCM enhancers. In this paper we illustrate the use of a Effective Thermal Conductivity (ETC) model for four different lattice structures to optimize a PCM based device for the thermal management of power electronics. The optimization is done in terms of device overall dimensions (especially its height) but also in term of composite (or enhanced PCM) enclosure. Actually the composite needs to be enclosed to avoid leaking but the enclosure also serves a heat spreading role which is studied here.