Prenatal exposure to environmentally relevant levels of PAHs inhibits spermatogenesis in adult mice and the mechanism involved.

Polycyclic aromatic hydrocarbons (PAHs) are a class of contaminants that cannot be banned. Exposure to PAHs has been reported to alter spermatogenesis in mammals, but little is known about prenatal exposure to a mixture of PAHs on the reproductive toxicity of adult offspring. In this study, we investigated the associations between prenatal exposure to environmentally relevant levels of PAHs in mice and testicular dysfunction, including impaired spermatogenesis and steroid hormone dysfunction in male offspring on postnatal day 180. The percentage of testicular apoptotic cells was significantly increased, which was further verified by the up-regulated BAX protein. The expression of Ar and the Leydig cell marker Cyp11a1 was down-regulated, suggesting an impairment in the synthesis of steroid hormones. DNA hypermethylation of the Tnp1 and Sohlh2 promoters suppresses transcriptional expression, consequently altering the sperm production process. This study shows that prenatal exposure to PAHs may induce long-term reproductive toxicity.

Involvement of M2 macrophages polarization in PM2.5-induced COPD by upregulating MMP12 via IL4/STAT6 pathway.

Biomass-related airborne fine particulate matter (PM2.5) is an important risk factor for chronic obstructive pulmonary disease (COPD). Macrophage polarization has been reported to be involved in PM2.5-induced COPD, but the dynamic characteristics and underlying mechanism of this process remain unclear. Our study established a PM2.5-induced COPD mouse model and revealed that M2 macrophages predominantly presented after 4 and 6 months of PM2.5 exposure, during which a notable increase in MMP12 was observed. Single cell analysis of lung tissues from COPD patients and mice further revealed that M2 macrophages were the dominant macrophage subpopulation in COPD, with MMP12 being involved as a hub gene. In vitro experiments further demonstrated that PM2.5 induced M2 polarization and increased MMP12 expression. Moreover, we found that PM2.5 increased IL-4 expression, STAT6 phosphorylation and nuclear translocation. Nuclear pSTAT6 then bound to the MMP12 promoter region. Furthermore, the inhibition of STAT6 phosphorylation effectively abrogated the PM2.5-induced increase in MMP12. Using a coculture system, we observed a significantly reduced level of E-cadherin in alveolar epithelial cells cocultured with PM2.5-exposed macrophages, while the decrease in E-cadherin was reversed by the addition of an MMP12 inhibitor to the co-culture system. Taken together, these findings indicated that PM2.5 induced M2 macrophage polarization and MMP12 upregulation via the IL-4/STAT6 pathway, which resulted in alveolar epithelial barrier dysfunction and excessive extracellular matrix (ECM) degradation, and ultimately led to COPD progression. These findings may help to elucidate the role of macrophages in COPD, and suggest promising directions for potential therapeutic strategies.

Machine learning-based analysis identifies and validates serum exosomal proteomic signatures for the diagnosis of colorectal cancer.

The potential of serum extracellular vesicles (EVs) as non-invasive biomarkers for diagnosing colorectal cancer (CRC) remains elusive. We employed an in-depth 4D-DIA proteomics and machine learning (ML) pipeline to identify key proteins, PF4 and AACT, for CRC diagnosis in serum EV samples from a discovery cohort of 37 cases. PF4 and AACT outperform traditional biomarkers, CEA and CA19-9, detected by ELISA in 912 individuals. Furthermore, we developed an EV-related random forest (RF) model with the highest diagnostic efficiency, achieving AUC values of 0.960 and 0.963 in the train and test sets, respectively. Notably, this model demonstrated reliable diagnostic performance for early-stage CRC and distinguishing CRC from benign colorectal diseases. Additionally, multi-omics approaches were employed to predict the functions and potential sources of serum EV-derived proteins. Collectively, our study identified the crucial proteomic signatures in serum EVs and established a promising EV-related RF model for CRC diagnosis in the clinic.

A Platelet-Powered Drug Delivery System for Enhancing Chemotherapy Efficacy for Liver Cancer Using the Trojan Horse Strategy.

Optimizing the delivery and penetration of nano-sized drugs within liver cancer sites, along with remodeling the tumor microenvironment, is crucial for enhancing the efficacy of chemotherapeutic agents. For this study, a platelet (PLT)-mediated nanodrug delivery system (DASA+ATO@PLT) was developed to improve the effectiveness of chemotherapy. This system delivers nano-sized dasatinib and atovaquone specifically to liver tumor sites and facilitates intra-tumoral permeation upon release. Through JC-1, immunohistochemistry, and DNA damage analyses, the therapeutic effect of DASA+ATO@PLT was assessed. In vitro simulation and intravital imaging were carried out to determine the accumulation of dasatinib and atovaquone in liver tumor sites. The experiment demonstrated the accumulation of dasatinib and atovaquone in tumor sites, followed by deep permeation in the tumor microenvironment with the assistance of PLTs, while simultaneously revealing the ability of DASA+ATO@PLT to remodel the liver cancer microenvironment (overcoming hypoxia) and enhance chemotherapeutic efficacy. This system utilizes the natural tumor recognition ability of PLTs and enhances the chemo-immunotherapeutic effect through targeted delivery of nano-chemotherapeutic drugs to the tumor, resulting in effective accumulation and infiltration. The PLT-mediated nanodrug delivery system serves as a "Trojan horse" to carry therapeutic drugs as cargo and deliver them to target cells, leading to favorable outcomes.

DECODE: Contamination-Free Digital CRISPR Platform for Point-of-Care Detection of Viral DNA/RNA.

Rapid and precise nucleic acid testing at the point-of-care (POC) is essential for effective screening and management of infectious diseases. Current polymerase-based molecular diagnostics often suffer from potential cross-contamination issues, particularly in POC settings. Here, we introduce DECODE, a contamination-free nucleic acid detection platform integrating digital microfluidics (DMF) for nucleic acid extraction and a digital CRISPR amplification-free assay for pathogen detection. The digital CRISPR assay demonstrates sensitivity, detecting target DNA and RNA in the reaction mixture at concentrations of 10 and 5 copies/µL, respectively. Leveraging DMF-extracted samples enhances the performance of the digital CRISPR amplification-free assay. DECODE offers a sample-to-result workflow of 75 min using compact devices. Validation studies using clinical samples confirm DECODE's robust performance, achieving 100% sensitivity and specificity in detecting HPV18 from cervical epithelial cells and influenza A from nasal swabs. DECODE represents a versatile, contamination-free detection platform poised to enhance integrated public health surveillance efforts.

Single-cell RNA transcriptome landscape of murine liver following systemic administration of mesoporous silica nanoparticles.

Due to the unique physicochemical properties, mesoporous silica nanoparticles (MONs) have been widely utilized in biomedical fields for drug delivery, gene therapy, disease diagnosis and imaging. With the extensive applications and large-scale production of MONs, the potential effects of MONs on human health are gaining increased attention. To better understand the cellular and molecular mechanisms underlying the effects of MONs on the mouse liver, we profiled the transcriptome of 63,783 single cells from mouse livers following weekly intravenous administration of MONs for 2 weeks. The results showed that the proportion of endothelial cells and CD4+ T cells was increased, whereas that of Kupffer cells was decreased, in a dose-dependent manner after MONs treatment in the mouse liver. We also observed that the proportion of inflammation-related Kupffer cell subtype and wound healing-related hepatocyte subtype were elevated, but the number of hepatocytes with detoxification characteristics was reduced after MONs treatment. The cell-cell communication network revealed that there was more crosstalk between cholangiocytes and Kupffer cells, liver capsular macrophages, hepatic stellate cells, and endothelial cells following MONs treatment. Furthermore, we identified key ligand-receptor pairs between crucial subtypes after MONs treatment that are known to promote liver fibrosis. Collectively, our study explored the effects of MONs on mouse liver at a single-cell level and provides comprehensive information on the potential hepatotoxicity of MONs.

Quercetin induces MGMT+ glioblastoma cells apoptosis via dual inhibition of Wnt3a/ß-Catenin and Akt/NF-κB signaling pathways.

BACKGROUND: Surgical resection combined with radiotherapy and chemotherapy remains a common clinical treatment for glioblastoma multiforme (GBM). However, the therapeutic outcomes have not been satisfying due to drug resistance and other factors. Quercetin, a phytoingredient capable of crossing the blood-brain barrier, has shown effectiveness in the treatment of various solid tumors. Nevertheless, the potential of quercetin in GBM treatment has not been adequately explored. PURPOSE: This study aims to investigate the effects and mechanisms of quercetin on MGMT+GBM cells. METHODS: The potential targets and mechanisms of quercetin in glioma treatment were predicted based on network pharmacology and molecular docking. The effects of quercetin on cell inhibition rate, cell migration ability, cell cycle arrest, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), Mitochondrial superoxide formation and apoptosis were measured by the CCK8 assay, wound healing assay, PI/RNase staining, JC-1 assay, DCFH-DA assay, MitoSOX staining and Annexin V-FITC/PI double staining, respectively. The methylation status of the MGMT promoter was assessed through methylation-specific polymerase chain reaction (MS-PCR). DNA damage was quantified by alkaline/neutral comet assay and TUNEL assay. The intracellular localization and expression of NF-κB and MGMT were revealed by immunofluorescence. The expression of migration-related proteins, matrix metalloproteinases, apoptosis-related proteins, cyclins, DNA damage/repair enzymes and related pathway proteins was detected by Western blot. RESULTS: Network pharmacology identified 96 targets and potential molecular mechanisms of quercetin in glioma treatment. Subsequent experiments confirmed the synergistic effect of quercetin in combination with temozolomide (TMZ) on T98G cells. Quercetin significantly suppressed the growth and migration of human GBM T98G cells, induced apoptosis, and arrested cells in the S-phase cell cycle. The collapse of mitochondrial membrane potential, ROS generation, enhanced Bax/Bcl-2 ratio, and strengthened cleaved-Caspase 9 and cleaved-Caspase 3 suggested the involvement of ROS-mediated mitochondria-dependent apoptosis in the process of quercetin-induced apoptosis. In addition, quercetin-induced apoptosis was accompanied by intense DNA double-strand breaks (DSBs), γH2AX foci formation, methylation of MGMT promoter, increased cleaved-PARP, and reduced MGMT expression. Quercetin may influence the expression of the key DNA repair enzyme, MGMT, by dual suppression of the Wnt3a/ß-Catenin and the Akt/NF-κB signaling pathways, thereby promoting apoptosis. Inhibition of Wnt3a and Akt using specific inhibitors hindered MGMT expression. CONCLUSION: Our study provides the first evidence that quercetin may induce apoptosis in MGMT+GBM cells via dual inhibition of the Wnt3a/ß-Catenin pathway and the Akt/NF-κB signaling pathway. These findings suggest that quercetin could be a novel agent for improving GBM treatment, especially in TMZ-resistant GBM with high MGMT expression.

Rasburicase-Induced Falsely Low Measurement of Uric Acid in Tumor Lysis Syndrome: A Report of Two Cases.

Rasburicase, a recombinant urate-oxidase enzyme, can significantly catalyze the oxidation of uric acid to allantoin. It was approved by the US Food and Drug Administration (FDA) to control blood uric acid levels in both pediatric and adult patients especially those with tumor lysis syndrome. It is quite important to realize that rasburicase can continue to be effective ex vivo and cause falsely low results if the blood sample is not contained and transported in ice water immediately. We presented two cases of falsely low measurement of blood uric acid caused by rasburicase and elaborated the proper method for collecting and transporting blood samples from patients using rasburicase.

Sodium danshensu attenuates cerebral ischemia-reperfusion injury by targeting AKT1.

The beneficial properties of Sodium Danshensu (SDSS) for controlling cerebral ischemia and reperfusion injury (CIRI) are elucidated here both in vivo and in vitro. SDSS administration significantly improved the viability of P12 cells, reduced lactate dehydrogenase (LDH) leakage, and decreased the apoptosis rate following exposure to an oxygen-glucose deprivation/reoxygenation (OGD) environment. In addition, the results of a HuprotTM human protein microarray and network pharmacology indicated that AKT1 is one of the main targets of SDSS. Moreover, functional experiments showed that SDSS intervention markedly increased the phosphorylation level of AKT1 and its downstream regulator, mTOR. The binding sites of SDSS to AKT1 protein were confirmed by Autodock software and a surface plasmon resonance experiment, the result of which imply that SDSS targets to the PH domain of AKT1 at ASN-53, ARG-86, and LYS-14 residues. Furthermore, knockdown of AKT1 significantly abolished the role of SDSS in protecting cells from apoptosis and necrosis. Finally, we investigated the curative effect of SDSS in a rat model of CIRI. The results suggest that administration of SDSS significantly reduces CIRI-induced necrosis and apoptosis in brain samples by activating AKT1 protein. In conclusion, SDSS exerts its positive role in alleviating CIRI by binding to the PH domain of AKT1 protein, further resulting in AKT1 activation.

CTRP1 prevents high fat diet-induced obesity and improves glucose homeostasis in obese and STZ-induced diabetic mice.

BACKGROUND: C1q/tumor necrosis factor-related protein 1 (CTRP1) is an adipokine secreted by adipose tissue, related to chondrocyte proliferation, inflammation, and glucose homeostasis. However, the therapeutic effects on metabolic disorders and the underlying mechanism were unclear. Here, we investigated the functions and mechanisms of CTRP1 in treating obesity and diabetes. METHODS: The plasmid containing human CTRP1 was delivered to mice by hydrodynamic injection, which sustained expression of CTRP1 in the liver and high protein level in the blood. High-fat diet (HFD) fed mice and STZ-induced diabetes model were used to study the effects of CTRP1 on obesity, glucose homeostasis, insulin resistance, and hepatic lipid accumulation. The lipid accumulation in liver and adipose tissue, glucose tolerance, insulin sensitivity, food intake, and energy expenditure were detected by H&E staining, Oil-Red O staining, glucose tolerance test, insulin tolerance test, and metabolic cage, respectively. The metabolic-related genes and signal pathways were determined using qPCR and western blotting. RESULTS: With high blood circulation, CTRP1 prevented obesity, hyperglycemia, insulin resistance, and fatty liver in HFD-fed mice. CTRP1 also improved glucose metabolism and insulin resistance in obese and STZ-induced diabetic mice. The metabolic cage study revealed that CTRP1 reduced food intake and enhanced energy expenditure. The mechanistic study demonstrated that CTRP1 upregulated the protein level of leptin in blood, thermogenic gene expression in brown adipose tissue, and the gene expression responsible for lipolysis and glycolysis in white adipose tissue (WAT). CTRP1 also downregulated the expression of inflammatory genes in WAT. Overexpression of CTRP1 activated AMPK and PI3K/Akt signaling pathways and inhibited ERK signaling pathway. CONCLUSION: These results demonstrate that CTRP1 could improve glucose homeostasis and prevent HFD-induced obesity and fatty liver through upregulating the energy expenditure and reducing food intake, suggesting CTRP1 may serve as a promising target for treating metabolic diseases.

A Feasible and Promising Strategy for Improving the Solar Selectivity and Thermal Stability of Cermet-Based Photothermal Conversion Coatings.

A novel multilayer, solar selective absorbing coating that contains lamellar-distributed nanoparticles in its cermet-absorbing sublayers has been fabricated using ion-source-assisted cathodic arc plating. The multilayer coating shows an outstanding selectivity, i.e., a high solar absorptance (0.909), yet it has a low thermal emittance (0.163). More importantly, the long-term thermal stability tests demonstrate that the lamellar-structured absorbers can remain stable, even when annealed at 500 °C for 1000 h in ambient air. The coating's enhanced selectivity and thermal stability were attributed to the formation of lamellar-distributed nanoparticles in the absorbing sublayer, which form many asymmetric Fabry-Pérot cavities. In this case, the light would be held in the Fabry-Pérot cavities and thus boost the absorptivity due to the increase in interaction time. Meanwhile, the unique distribution of the nanoparticles is also beneficial for enhancing the surface plasmon resonance absorption, and thus promoting the increase in solar selectivity. Furthermore, the excellent thermal stability is ascribed to the existence of amorphous matrices, which separate and seal the nanoparticles into honeycomb shells. In this case, the atomic diffusion in the nanoparticles would be significantly retarded as the amorphous matrices can remain stable below the crystallization temperatures, which can effectively slow down the growth and agglomeration of the nanoparticles.

Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care.

One of the most effective treatments for diabetes is to design a glucose-regulated insulin (INS) delivery system that could adjust the INS release time and rate to reduce diabetes-related complications. Here, mixed multiple layer-by-layer (mmLbL)-INS microspheres were developed for glucose-mediated INS release and an enhanced hypoglycemic effect for diabetes care. To achieve ultrafast glucose-activated INS release, glucose oxidase (GOx) was assembled with a positively charged polymer and modified on INS LbL. The mmLbL-INS microspheres were constructed with one, two, and four layers of the polyelectrolyte LbL assembly at a ratio of 1:1:1. Under hyperglycemia, GOx converts a change in the hyperglycemic environment to a pH stimulus, thus providing sufficient hydrogen ion. The accumulated hydrogen ion starts LbL charge shifting, and anionic polymers are converted to cationic polymers through hydrolytic cleavage of amine-functionalized side chains. The results of in vitro INS release suggested that glucose can modulate the mmLbL-INS microspheres in a pulsatile profile. In vivo studies validated that this formulation enhanced the hypoglycemic effect in STZ-induced diabetic rats within 2 h of subcutaneous administration and facilitated stabilization of blood glucose levels for up to 2 days. This glucose-activatable LbL microsphere system could serve as a powerful tool for constructing a precisely controlled release system.

Effects of combination treatment with metformin and berberine on hypoglycemic activity and gut microbiota modulation in db/db mice.

BACKGROUND: Gut microbiota alterations could influence the metabolism of administered drugs, leading to their altered pharmacokinetics and pharmacodynamics. Despite that metformin and berberine has individually demonstrated their impacts on hypoglycemic activities and gut microbiota alterations in diabetic mice, investigation regarding the impact of their combination treatment in diabetic treatment has never been conducted. PURPOSE: Our current study was proposed aiming to investigate the effect of combination use of metformin with berberine on hypoglycemic activity and identify the possible intestinal bacteria involved in their microbiota-medicated drug-drug interactions in db/db mice. STUDY DESIGN: Pharmacodynamics interactions between metformin and berberine were evaluated in six groups of db/db mice (db, M250, B250, B125, B250+M250, and B125+M250) with its wild type (WT) as control to receive 14 days treatment of vehicle, metformin at 250 mg/kg, berberine at 250/125 mg/kg, and metformin (250 mg/kg) 2 h after dosing berberine (250/125 mg/kg). METHODS: On day 13, insulin tolerance test (ITT) was conducted. On day 15, fasting serum samples were obtained for insulin concentration determination followed by intraperitoneal glucose tolerance test (ipGTT), homeostatic model assessment for insulin resistance (HOMA-IR) calculation, and feces collection for microbial 16S rRNA sequencing analyses. In addition, metformin steady state plasma concentrations on day 15 were measured by validated LC-MS/MS method. RESULTS: Combination treatment of metformin with berberine could further reduce in blood glucose in comparison to that of db/db diabetic control. Further microbial 16S rRNA sequencing analyses revealed that gut microbiota compositions were significantly changed with the abundance of Proteobacteria and Verrucomicrobia altered the most after metformin and berberine co-treatment compared to their monotherapy. In addition, steady state metformin concentrations in their combination treatment were significantly higher than that from metformin monotherapy. CONCLUSION: Co-administration of metformin (250 mg/kg) with berberine (125 mg/kg) could not only further improve insulin sensitivity, but also demonstrate different alterations on gut microbial communities than that of their individual treatment in db/db mice.

Comprehensive analysis of peripheral blood non-coding RNAs identifies a diagnostic panel for fungal infection after transplantation.

The occurrence of fungal infection seriously affects the survival and life quality of transplanted patients. The accurate diagnosis is of particular importance in the early stage of infection. To develop a novel diagnostic method for this kind of patient, we established a post-transplant immunosuppressed mice model with fungus inoculation and collected their peripheral blood at specific time points after infection. After screening by microarray, differentially expressed miRNAs and lncRNAs were selected and homologously analyzed with those of human beings from the gene database. These miRNAs and lncRNAs candidates were validated by qRT-PCR in peripheral blood samples from transplanted patients. We found that, compared with normal transplanted patients, the levels of miR-215 and miR-let-7 c were up-regulated in the plasma of patients with fungal infection (P < 0.01), while levels of miR-154, miR-193a, NR_027669.1, and NR_036506.1 were down-regulated in their peripheral blood mononuclear cells (P < 0.01). Principal component analysis shows that the expression pattern of the above RNAs was different between the two groups. A 6-noncoding-RNA detection panel was established by the support vector machine analysis, whose area under the ROC curve was 0.927. The accuracy, precision, sensitivity, and specificity of this model were 0.928, 0.919, 0.944, and 0.910, respectively. Though our detection panel has excellent diagnostic efficacy, its clinical application value still needs to be further confirmed by multi-center prospective clinical trials.

The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis.

Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is involved in multiple biological functions in cell development, differentiation, and transcriptional regulation. Tet1 deficient mice display the defects of murine glucose metabolism. However, the role of TET1 in metabolic homeostasis keeps unknown. Here, our finding demonstrates that hepatic TET1 physically interacts with silent information regulator T1 (SIRT1) via its C-terminal and activates its deacetylase activity, further regulating the acetylation-dependent cellular translocalization of transcriptional factors PGC-1α and FOXO1, resulting in the activation of hepatic gluconeogenic gene expression that includes PPARGC1A, G6PC, and SLC2A4. Importantly, the hepatic gluconeogenic gene activation program induced by fasting is inhibited in Tet1 heterozygous mice livers. The adenosine 5'-monophosphate-activated protein kinase (AMPK) activators metformin or AICAR-two compounds that mimic fasting-elevate hepatic gluconeogenic gene expression dependent on in turn activation of the AMPK-TET1-SIRT1 axis. Collectively, our study identifies TET1 as a SIRT1 coactivator and demonstrates that the AMPK-TET1-SIRT1 axis represents a potential mechanism or therapeutic target for glucose metabolism or metabolic diseases.

Effective Plug-Ins for Reducing Inference-Latency of Spiking Convolutional Neural Networks During Inference Phase.

Convolutional Neural Networks (CNNs) are effective and mature in the field of classification, while Spiking Neural Networks (SNNs) are energy-saving for their sparsity of data flow and event-driven working mechanism. Previous work demonstrated that CNNs can be converted into equivalent Spiking Convolutional Neural Networks (SCNNs) without obvious accuracy loss, including different functional layers such as Convolutional (Conv), Fully Connected (FC), Avg-pooling, Max-pooling, and Batch-Normalization (BN) layers. To reduce inference-latency, existing researches mainly concentrated on the normalization of weights to increase the firing rate of neurons. There are also some approaches during training phase or altering the network architecture. However, little attention has been paid on the end of inference phase. From this new perspective, this paper presents 4 stopping criterions as low-cost plug-ins to reduce the inference-latency of SCNNs. The proposed methods are validated using MATLAB and PyTorch platforms with Spiking-AlexNet for CIFAR-10 dataset and Spiking-LeNet-5 for MNIST dataset. Simulation results reveal that, compared to the state-of-the-art methods, the proposed method can shorten the average inference-latency of Spiking-AlexNet from 892 to 267 time steps (almost 3.34 times faster) with the accuracy decline from 87.95 to 87.72%. With our methods, 4 types of Spiking-LeNet-5 only need 24-70 time steps per image with the accuracy decline not more than 0.1%, while models without our methods require 52-138 time steps, almost 1.92 to 3.21 times slower than us.

Successful single kidney transplantation from pediatric donors less than or equal to 10 kg to adult recipient: a retrospective cohort study.

BACKGROUND: Kidneys from very small pediatric donors (≤10 kg) are underutilized. Compared to en bloc kidney transplantation (EBKT), single kidney transplantation (SKT) can maximize donor resources. However, it remains unknown whether it's appropriate to perform SKTs from donors weighing ≤10 kg. METHODS: A total of 35 adult recipients undergoing kidney transplantation from donors weighing ≤10 kg at our center from December 2014 to December 2019 were included and grouped into SKT group (n=20) and EBKT group (n=15). Transplant outcomes were retrospectively analyzed and compared between 2 groups. RESULTS: The 1-year and 3-year death-censored graft survival in SKT group was 95%, it is not significantly higher than that in EBKT group (80%, log-rank test, P=0.38). Significant improvement in estimated glomerular filtration rate (eGFR) was noted in both groups, despite eGFR at 1 year was lower in the SKT group (P<0.01). Proteinuria was common in both groups but subsided gradually during the follow-up time. Complication rates were similar between 2 groups with no vascular thrombosis in the SKT group. CONCLUSIONS: In conclusion, SKTs from donors weighing ≤10 kg to adult recipients achieves comparable outcomes with EBKTs, which provides evidence to support performing SKTs from donors weighing ≤10 kg in certain donor and recipient scenarios.

The Global Infectious Diseases Epidemic Information Monitoring System: Development and Usability Study of an Effective Tool for Travel Health Management in China.

BACKGROUND: Obtaining comprehensive epidemic information for specific global infectious diseases is crucial to travel health. However, different infectious disease information websites may have different purposes, which may lead to misunderstanding by travelers and travel health staff when making accurate epidemic control and management decisions. OBJECTIVE: The objective of this study was to develop a Global Infectious Diseases Epidemic Information Monitoring System (GIDEIMS) in order to provide comprehensive and timely global epidemic information. METHODS: Distributed web crawler and cloud agent acceleration technologies were used to automatically collect epidemic information about more than 200 infectious diseases from 26 established epidemic websites and Baidu News. Natural language processing and in-depth learning technologies have been utilized to intelligently process epidemic information collected in 28 languages. Currently, the GIDEIMS presents world epidemic information using a geographical map, including date, disease name, reported cases in different countries, and the epidemic situation in China. In order to make a practical assessment of the GIDEIMS, we compared infectious disease data collected from the GIDEIMS and other websites on July 16, 2019. RESULTS: Compared with the Global Incident Map and Outbreak News Today, the GIDEIMS provided more comprehensive information on human infectious diseases. The GIDEIMS is currently used in the Health Quarantine Department of Shenzhen Customs District (Shenzhen, China) and was recommended to the Health Quarantine Administrative Department of the General Administration of Customs (China) and travel health-related departments. CONCLUSIONS: The GIDEIMS is one of the most intelligent tools that contributes to safeguarding the health of travelers, controlling infectious disease epidemics, and effectively managing public health in China.

Gdf11 gene transfer prevents high fat diet-induced obesity and improves metabolic homeostasis in obese and STZ-induced diabetic mice.

BACKGROUND: The growth differentiation factor 11 (GDF11) was shown to reverse age-related hypertrophy on cardiomyocytes and considered as anti-aging rejuvenation factor. The role of GDF11 in regulating metabolic homeostasis is unclear. In this study, we investigated the functions of GDF11 in regulating metabolic homeostasis and energy balance. METHODS: Using a hydrodynamic injection approach, plasmids carrying a mouse Gdf11 gene were delivered into mice and generated the sustained Gdf11 expression in the liver and its protein level in the blood. High fat diet (HFD)-induced obesity was employed to examine the impacts of Gdf11 gene transfer on HFD-induced adiposity, hyperglycemia, insulin resistance, and hepatic lipid accumulation. The impacts of GDF11 on metabolic homeostasis of obese and diabetic mice were examined using HFD-induced obese and STZ-induced diabetic models. RESULTS: Gdf11 gene transfer alleviates HFD-induced obesity, hyperglycemia, insulin resistance, and fatty liver development. In obese and STZ-induced diabetic mice, Gdf11 gene transfer restores glucose metabolism and improves insulin resistance. Mechanism study reveals that Gdf11 gene transfer increases the energy expenditure of mice, upregulates the expression of genes responsible for thermoregulation in brown adipose tissue, downregulates the expression of inflammatory genes in white adipose tissue and those involved in hepatic lipid and glucose metabolism. Overexpression of GDF11 also activates TGF-ß/Smad2, PI3K/AKT/FoxO1, and AMPK signaling pathways in white adipose tissue. CONCLUSIONS: These results demonstrate that GDF11 plays an important role in regulating metabolic homeostasis and energy balance and could be a target for pharmacological intervention to treat metabolic disease.

Simple strategy for single-chain fragment antibody-conjugated probe construction.

AIMS: A combination of biomarker and instrument technology diagnosis methods, especially antigen-targeted imaging methods, is required to increase the accuracy of the diagnosis of cancer. Currently, the targeting efficiency is limited by the conjugation methods used for the conjugation of antibodies and imaging materials. Here, a simple strategy for the conjugation of a probe and a single-chain fragment antibody (scFv) that does not change the characteristics of the antibody was shown. MAIN METHODS: An ScFv was conjugated with superparamagnetic iron oxide (SPIO) or indocyanine green (ICG) via a linker by utilizing the reaction between cysteine and maleimide. The characterization of the probe was performed by flow cytometry, confocal imaging, optical imaging and magnetic resonance imaging (MRI). KEY FINDINGS: After conjugation, the scFv retained high affinity, antigen specificity, and strong internalization ability. The application of the conjugated probe was also confirmed by optical imaging and MRI. SIGNIFICANCE: The proposed strategy provides a simple method for the production of high efficiency antigen-targeted imaging probes for tumor diagnosis.