GINS1 promotes ZEB1-mediated epithelial-mesenchymal transition and tumor metastasis via ß-catenin signaling in hepatocellular carcinoma.

GINS1 regulates DNA replication in the initiation and elongation phases and plays an important role in the progression of various malignant tumors. However, the role of GINS1 in hepatocellular carcinoma (HCC) remains largely unclear. In this study, we investigated the role and underlying mechanisms of GINS1 in contributing to HCC metastasis. We found that GINS1 was significantly upregulated in HCC tissues and cell lines, especially in HCC tissues with vascular invasion and HCC cell lines with highly metastatic properties. Additionally, high expression of GINS1 was positively correlated with the progressive clinical features of HCC patients, including tumor number (multiple), tumor size (>5 cm), advanced tumor stage, vascular invasion and early recurrence, suggesting that GINS1 upregulation was greatly involved in HCC metastasis. Moreover, Kaplan-Meier survival analysis revealed that high GINS1 expression predicted a poor prognosis. Both in vitro and in vivo, silencing of GINS1 inhibited proliferation, migration, invasion and metastasis, while overexpression of GINS1 induced opposite effects. Mechanistically, we found that ZEB1 was a crucial regulator of GINS1-induced epithelial-mesenchymal transition (EMT), and GINS1 promoted EMT and tumor metastasis through ß-catenin signaling. Overall, the present study demonstrated that GINS1 promoted ZEB1-mediated EMT and tumor metastasis via ß-catenin signaling in HCC.

Surficial Host-Guest Responsive CsPbBr3 Perovskite Nanocrystals for Programmable Multi-Level Information Encryption.

The design of smart stimuli-responsive photoluminescent materials capable of multi-level encryption and complex information storage is highly sought after in the current information era. Here, a novel adamantyl-capped CsPbBr3 (AD-CsPbBr3 ) perovskite NCs, along with its supramolecular host-guest assembly partner a modified ß-CD (mCD), mCD@AD-CsPbBr3 , are designed and prepared. By dispersing these two materials in different solvents, namely, AD-CsPbBr3 in toluene, mCD@AD-CsPbBr3 in toluene, and mCD@AD-CsPbBr3 in methanol, the three solutions exhibit diverse photoluminescence (PL) turn-on/off or PL discoloration response upon supramolecular stimulus. Based on these responses, a proof-of-principle programmable Multi-Level Photoluminescence Encoding System (MPLES) is established. Three types of four-level and three types of three-level information encoding are achieved by the system. A layer-by-layer four-level information encryption and decryption as well as a two-level encrypted 3D code are successfully achieved.

Stereo-Active Lone Pairs Induced Second Harmonic Generation Responses and Electrocatalytic Activity in Hybrid Material.

The lone pair electrons in the electronic structure of molecules have been a prominent research focus in chemistry for more than a century. Stable s2lone pair electrons significantly influence material properties, including thermoelectric properties, nonlinear optical properties, ferroelectricity, and electro(photo)catalysis.While major advances have been achieved in understanding the influence of lone pair electrons on material characteristics, research on this effect in organic-inorganic hybrid materials is in its initial stage. In this work, we successfully obtained a novel organic-inorganic hybrid material incorporating Ge with 4s2 lone pair electrons, (MeHDabco)2[GeBr3]4-H2O (MeHDabco = N-methyl-1,4-diazabicyclo[2.2.2]octane) (1). Driven by the stereochemically active lone pair electrons on the Ge2+, 1 crystallizes in the noncentrosymmetric space group P21 at room temperature and exhibits good second harmonic generation (SHG) responses. Interestingly, 1 also shows electrocatalytic activity for the hydrogen evolution reaction due to the existence of lone pair electrons on Ge2+ cations. The electrochemical experiment combined with the DFT calculations revealed the lone pair electrons act as both an active site for proton adsorption and facilitate the ionization of water. This work not only emphasizes the important role of lone pair electrons in material properties and functions but also provides new insight for designing novel Ge-based hybrid materials.

A Guanosine-Derived Antitumor Supramolecular Prodrug.

The prodrug strategy for its potential to enhance the pharmacokinetic and/or pharmacodynamic properties of drugs, especially chemotherapeutic agents, has been widely recognized as an important means to improve therapeutic efficiency. Irinotecan's active metabolite, 7-ethyl-10-hydroxycamptothecin (SN38), a borate derivative, was incorporated into a G-quadruplex hydrogel (GB-SN38) by the ingenious and simple approach. Drug release does not depend on carboxylesterase, thus bypassing the side effects caused by ineffective activation, but specifically responds to the ROS-overexpressed tumor microenvironment by oxidative hydrolysis of borate ester that reduces serious systemic toxicity from nonspecific biodistribution of SN38. Comprehensive spectroscopy was used to define the structural and physicochemical characteristics of the drug-loaded hydrogel. The GB-SN38 hydrogel's high level of biosafety and notable tumor-suppressive properties were proven in in vitro and in vivo tests.

A Dual-mode platform for the rapid detection of Escherichia coli O157:H7 based on CRISPR/Cas12a and RPA.

Escherichia coli O157:H7 (E. coli O157:H7) is a foodborne pathogenic microorganism that is commonly found in the environment and poses a significant threat to human health, public safety, and economic stability worldwide. Thus, early detection is essential for E. coli O157:H7 control. In recent years, a series of E. coli O157:H7 detection methods have been developed, but the sensitivity and portability of the methods still need improvement. Therefore, in this study, a rapid and efficient testing platform based on the CRISPR/Cas12a cleavage reaction was constructed. Through the integration of recombinant polymerase amplification and lateral flow chromatography, we established a dual-interpretation-mode detection platform based on CRISPR/Cas12a-derived fluorescence and lateral flow chromatography for the detection of E. coli O157:H7. For the fluorescence detection method, the limits of detection (LODs) of genomic DNA and E. coli O157:H7 were 1.8 fg/µL and 2.4 CFU/mL, respectively, within 40 min. Conversely, for the lateral flow detection method, LODs of 1.8 fg/µL and 2.4 × 102 CFU/mL were achieved for genomic DNA and E. coli O157:H7, respectively, within 45 min. This detection strategy offered higher sensitivity and lower equipment requirements than industry standards. In conclusion, the established platform showed excellent specificity and strong universality. Modifying the target gene and its primers can broaden the platform's applicability to detect various other foodborne pathogens.

Baicalein triggers ferroptosis in colorectal cancer cells via blocking the JAK2/STAT3/GPX4 axis.

Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 µM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 µM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 µM), necroptosis inhibitor necrostatin-1 (10 µM), or pan-caspase inhibitor Z-VAD-FMK (10 µM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect of baicalein on CRC cells is associated with ferroptosis induction. We revealed that baicalein (7.5-30 µM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.

Effect of resuscitation of cryopreserved porcine adrenal glands at 26 °C on their recovery and functioning under xenotransplantation.

The study is devoted to the effect of lowered resuscitation temperature (26 °C) on cryopreserved porcine adrenal glands functional activity in vitro and in vivo under xenotransplantation. The adrenals were collected from newborn pigs, cryopreserved with 5 % DMSO at a rate of 1 °C/min, resuscitated at 26 or 37 °C for 48 h (5 % CO2, DMEM), embedded into small intestinal submucosa, and transplanted to bilaterally adrenalectomized rats. It has been shown that the glands resuscitated at 26 °C have suppressed free-radical processes and can produce cortisol and aldosterone in vitro, and may lead to elevated blood levels of these hormones. Moreover, the adrenal grafts maintain blood glucose levels and promote the formation of glycogen stores. Thus, the resuscitation at 26 °C can improve the quality of grafts and favor the introduction and application of the cryopreserved organs and tissues for transplantation in clinical and experimental practice.

Associations between UGT1A1, SLCO1B1, SLCO1B3, BLVRA and HMOX1 polymorphisms and susceptibility to neonatal severe hyperbilirubinemia in Chinese Han population.

BACKGROUND: Severe neonatal hyperbilirubinemia could lead to kernicterus and neonatal death. This study aimed to analyze the association between single nucleotide polymorphisms in genes involved in bilirubin metabolism and the incidence of severe hyperbilirubinemia. METHODS: A total of 144 neonates with severe hyperbilirubinemia and 50 neonates without or mild hyperbilirubinemia were enrolled in 3 institutions between 2019 and 2020. Twelve polymorphisms of 5 genes (UGT1A1, SLCO1B1, SLCO1B3, BLVRA, and HMOX1) were analyzed by PCR amplification of genomic DNA. Genotyping was performed using an improved multiplex ligation detection reaction technique based on ligase detection reaction. RESULTS: The frequencies of the A allele in UGT1A1-rs4148323 and the C allele in SLCO1B3-rs2417940 in the severe hyperbilirubinemia group (30.2% and 90.6%, respectively) were significantly higher than those in the controls (30.2% vs.13.0%, 90.6% vs. 78.0%, respectively, both p < 0.05). Haplotype analysis showed the ACG haplotype of UGT1A1 were associated with an increased hyperbilirubinemia risk (OR 3.122, p = 0.001), whereas the GCG haplotype was related to a reduced risk (OR 0.523, p = 0.018). CONCLUSION: The frequencies of the A allele in rs4148323 and the C allele in rs2417940 are highly associated with the incidence of severe hyperbilirubinemia in Chinese Han neonates. TRIAL REGISTRATION: Trial registration number:ChiCTR1800020424; Date of registration:2018-12-29.

Lipid Metabolism-Related Gene Markers Used for Prediction Prognosis, Immune Microenvironment, and Tumor Stage of Pancreatic Cancer.

Recently, more and more evidence shows that lipid metabolism disorder has been observed in tumor, which impacts tumor cell proliferation, survival, invasion, metastasis, and response to the tumor microenvironment (TME) and tumor treatment. However, hitherto there has not been sufficient research to demonstrate the role of lipid metabolism in pancreatic cancer. This study contrives to get an insight into the relationship between the characteristics of lipid metabolism and pancreatic cancer. We collected samples of patients with pancreatic cancer from the Gene Expression Omnibus (GEO), the Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and the International Cancer Genome Consortium (ICGC) databases. Firstly, we implemented univariate regression analysis to get prognosis-related lipid metabolism genes screened and a construction of protein-protein interaction (PPI) network ensued. Then, contingent on our screening results, we explored the molecular subtypes mediated by lipid metabolism-related genes and the correlated TME cell infiltration. Additionally, we studied the disparately expressed genes among disparate lipid metabolism subtypes and established a scoring model of lipid metabolism-related characteristics using the least absolute shrinkage and selection operator (LASSO) regression analysis. At last, we explored the relationship between the scoring model and disease prognosis, tumor stage, tumor microenvironment, and immunotherapy. Two subtypes, C1 and C2, were identified, and lipid metabolism-related genes were studied. The result indicated that the patients with subtype C2 have a significantly lower survival rate than that of the patients with subtype C1, and we found difference in abundance of different immune-infiltrating cells. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed the association of these differentially expressed genes with functions and pathways related to lipid metabolism. Finally, we established a scoring model of lipid metabolism-related characteristics based on the disparately expressed genes. The results show that our scoring model have a substantial effect on forecasting the prognosis of patients with pancreatic cancer. The lipid metabolism model is an important biomarker of pancreatic cancer. Using the model, the relationship between disease prognosis, molecular subtypes, TME cell infiltration characteristics, and immunotherapy in pancreatic cancer patients could be explored.

Research on the Application of Molecular Image Processing in Rice Quality Inspection.

Objective: With the improvement of living standards, consumers are paying more and more attention to the quality of rice. Traditional rice quality detection relies on human sensory judgment, which is inaccurate and inefficient. With the continuous development of molecular imaging technology, more and more scholars at home and abroad have begun to pay attention to its application in the nondestructive testing of agricultural products. Molecular imaging technology combines the advantages of spectral technology and image technology, which can achieve rapid, nondestructive and accurate detection of rice quality. In this paper, taking rice as the research object, we carried out nondestructive detection research on rice varieties, moisture and starch content using molecular imaging technology. We proposed a rapid detection method based on molecular imaging technology for rice variety identification, moisture content and starch content. Molecular images of the rice samples from four origins were obtained using a molecular imaging system, the regions of interest of the rice were identified and, spectral data, textural features and morphological features of the rice were extracted. Spectral, textural and morphological features were selected by principal component analysis (PCA), and nine feature wavelengths were obtained and an optimal model was established with an accuracy of 91.67%, which demonstrated the feasibility of molecular imaging. By comparing the models, the BCC-LS-SVR model based on the RB function had the highest accuracy with R2 of 0.989, RMSEP of 0.767%, R2 of 0.985, and RMSEC of 0.591%. Moreover, starchy rice was detected using molecular imaging. The PCA-SVR model based on the RBF kernel function had the highest accuracy with R2 of 0.989, RMSEC of 0.445%, R2 of 0.991, and RMSEP of 0.669%. Our models demonstrated high accuracy in identifying rice varieties, as well as quantifying moisture and starch content, showcasing the feasibility of molecular imaging technology in rice quality assessment. This research offers a rapid, nondestructive, and accurate method for rice quality assessment, promising significant benefits for agricultural producers and consumers.

Oral Hydrogel Microbeads-Mediated In Situ Synthesis of Selenoproteins for Regulating Intestinal Immunity and Microbiota.

Selenoprotein plays a crucial role in immune cells and inflammatory regulation. However, as a protein drug that is easily denatured or degraded in the acidic environment of the stomach, efficient oral delivery of selenoprotein is a great challenge. Herein, we innovated an oral hydrogel microbeads-based biochemical strategy that can in situ synthesize selenoproteins, therefore bypassing the necessity and harsh conditions for oral protein delivery while effectively generating selenoproteins for therapeutic applications. The hydrogel microbeads were synthesized by coating hyaluronic acid-modified selenium nanoparticles with a protective shell of calcium alginate (SA) hydrogel. We tested this strategy in mice with inflammatory bowel disease (IBD), one of the most representative diseases related to intestinal immunity and microbiota. Our results revealed that hydrogel microbeads-mediated in situ synthesis of selenoproteins could prominently reduce proinflammatory cytokines secretion and mediate immune cells (e.g., reduce neutrophils and monocytes and increase immune regulatory T cells) to effectively relieve colitis-associated symptoms. This strategy was also able to regulate gut microbiota composition (increase probiotics abundance and suppress detrimental communities) to maintain intestinal homeostasis. Considering intestinal immunity and microbiota widely associated with cancers, infections, inflammations, etc., this in situ selenoprotein synthesis strategy might also be possibly applied to broadly tackle various diseases.

CAFs shape myeloid-derived suppressor cells to promote stemness of intrahepatic cholangiocarcinoma through 5-lipoxygenase.

BACKGROUND AND AIMS: We previously demonstrated that cancer-associated fibroblasts (CAFs) promote tumor growth through recruitment of myeloid-derived suppressor cells (MDSCs). 5-lipoxygenase (5-LO) is highly expressed in myeloid cells and is critical for synthesizing leukotriene B4 (LTB4), which is involved in tumor progression by activating its receptor leukotriene B4 receptor type 2 (BLT2). In this study, we investigated whether and how CAFs regulate MDSC function to enhance cancer stemness, the driving force of the cancer aggressiveness and chemotherapy refractoriness, in highly desmoplastic intrahepatic cholangiocarcinoma (ICC). APPROACH AND RESULTS: RNA-sequencing analysis revealed enriched metabolic pathways but decreased inflammatory pathways in cancer MDSCs compared with blood MDSCs from patients with ICC. Co-injection of ICC patient-derived CAFs promoted cancer stemness in an orthotopic ICC model, which was blunted by MDSC depletion. Conditioned media (CM) from CAF-educated MDSCs drastically promoted tumorsphere formation efficiency and stemness marker gene expression in ICC cells. CAF-CM stimulation increased expression and activity of 5-LO in MDSCs, while 5-LO inhibitor impaired the stemness-enhancing capacity of MDSCs in vitro and in vivo. Furthermore, IL-6 and IL-33 primarily expressed by CAFs mediated hyperactivated 5-LO metabolism in MDSCs. We identified the LTB4-BLT2 axis as the critical downstream metabolite signaling of 5-LO in promoting cancer stemness, as treatment with LTB4 was elevated in CAF-educated MDSCs, or blockade of BLT2 (which was preferentially expressed in stem-like ICC cells) significantly reduced stemness-enhancing effects of CAF-educated MDSCs. Finally, BLT2 blockade augmented chemotherapeutic efficacy in ICC patient-derived xenograft models. CONCLUSIONS: Our study reveals a role for CAFs in orchestrating the optimal cancer stemness-enhancing microenvironment by educating MDSCs, and suggests the 5-LO/LTB4-BLT2 axis as promising therapeutic targets for ICC chemoresistance by targeting cancer stemness.

Amplifying a Zeptonewton Force with a Single-Ion Nonlinear Oscillator.

Nonlinear mechanical resonators display rich and complex dynamics and are important in many areas of fundamental and applied sciences. Here, we present a general strategy to generate mechanical nonlinearities for trapped particles by transverse driving in a funnel-shaped potential. Employing a trapped ion platform, we study the nonlinear oscillation, bifurcation, and hysteresis of a single calcium ion and demonstrate a 20-fold enhancement of the signal from a zeptonewton-magnitude harmonic force through the effect of vibrational resonance. Our results represent a first step in combining the rich nonlinear dynamics with the precision control over mechanical motions offered by atomic physics and open up possibilities for exploiting nonlinear mechanical phenomena in the quantum regime.

Characterization of neuroinflammation pattern in anti-LGI1 encephalitis based on TSPO PET and symptom clustering analysis.

PURPOSE: TSPO PET with radioligand [18F]DPA-714 is an emerging molecular imaging technique that reflects cerebral inflammation and microglial activation, and it has been recently used in central nervous system diseases. In this study, we aimed to investigate the neuroinflammation pattern of anti-leucine-rich glioma-inactivated 1 (LGI1) protein autoimmune encephalitis (AIE) and to evaluate its possible correlation with clinical phenotypes. METHODS: Twenty patients with anti-LGI1 encephalitis from the autoimmune encephalitis cohort in Huashan Hospital and ten with other AIE and non-inflammatory diseases that underwent TSPO PET imaging were included in the current study. Increased regional [18F]DPA-714 retention in anti-LGI1 encephalitis was detected on a voxel basis using statistic parametric mapping analysis. Multiple correspondence analysis and hierarchical clustering were conducted for discriminate subgroups in anti-LGI1 encephalitis. Standardized uptake value ratios normalized to the cerebellum (SUVRc) were calculated for semiquantitative analysis of TSPO PET features between different LGI1-AIE subgroups. RESULTS: Increased regional retention of [18F]DPA-714 was identified in the bilateral hippocampus, caudate nucleus, and frontal cortex in LGI1-AIE patients. Two subgroups of LGI1-AIE patients were distinguished based on the top seven common symptoms. Patients in cluster 1 had a high frequency of facio-brachial dystonic seizures than those in cluster 2 (p = 0.004), whereas patients in cluster 2 had a higher frequency of general tonic-clonic (GTC) seizures than those in cluster 1 (p < 0.001). Supplementary motor area and superior frontal gyrus showed higher [18F]DPA-714 retention in cluster 2 patients compared with those in cluster 1 (p = 0.024; p = 0.04, respectively). CONCLUSIONS: Anti-LGI1 encephalitis had a distinctive molecular imaging pattern presented by TSPO PET scan. LGI1-AIE patients with higher retention of [18F]DPA-714 in the frontal cortex were more prone to present with GTC seizures. Further studies are required for verifying its value in clinical application.

Immunotherapies for the Effective Treatment of Primary Autoimmune Cerebellar Ataxia: a Case Series.

Primary autoimmune cerebellar ataxia (PACA) is an idiopathic sporadic cerebellar ataxia that is thought to be immune-mediated but lacks biomarkers or a known cause. Here, we report two cases of immune-mediated cerebellar ataxia that responded favorably to immunotherapy, in which tissue-based indirect immunofluorescence test for serum or cerebrospinal fluid (CSF) samples yielded positive results. Case 1 was a 78-year-old man who presented with subacute progressive gait ataxia with truncal instability and dysarthria in response to steroids. Case 2 was a 62-year-old man who presented with relapses and remissions of acute progressive cerebellar ataxia occurring 1-2 times per year. Despite a favorable response to steroid treatment, he relapsed repeatedly in the absence of long-term immunosuppression. In the case of "idiopathic" cerebellar ataxia, immune-mediated causes should be investigated, and immunotherapy may have therapeutic effects.

Association of glycation gap with all-cause and cardiovascular mortality in US adults: A nationwide cohort study.

AIM: To investigate the relationship of the glycation gap (GGap) with all-cause and cardiovascular (CV) mortality in US adults. METHODS: This was a retrospective cohort study comprising 12 909 individual participant data from the National Health and Nutrition Examination Survey from 1999 to 2004 and their mortality data through 31 December 2019. Weighted Cox proportional hazards regression models and restricted cubic splines were used to investigate the associations between GGap and mortality. RESULTS: During a median follow-up of 16.8 years, 3528 deaths occurred, including 1140 CV deaths. The associations of GGap with risk of all-cause and CV mortality were U-shaped (both P for non-linearity < .001). Compared with individuals with a GGap of 0.09%-0.38% (61st-80th centiles), the multivariable-adjusted HRs and 95% CIs for individuals with a GGap less than -0.83% (first-fifth centiles) and individuals with a GGap greater than 0.90% (96th-100th centiles) were 1.36 (1.10, 1.69) and 1.21 (1.00, 1.45) for all-cause mortality, and 1.77 (1.16, 2.71) and 1.43 (1.04, 1.95) for CV mortality. The GGap value associated with the lowest risk of all-cause and CV mortality was 0.38% in the general population and 0.78% among individuals with diabetes. CONCLUSIONS: We found a U-shaped association between GGap and all-cause and CV mortality, with significant positive or negative GGap values associated with increased mortality risk, probably because of glycaemic variability and fructosamine-3-kinase activity.

Homochiral Chemistry Strategy to Trigger Second-Harmonic Generation and Dual Dielectric Switches.

Switchable materials have attracted enormous interest due to their promising applications in important fields such as sensing, electronic components, and information storage. Nevertheless, obtaining multifunctional switching materials is still a problem worth investigating. Herein, by incorporating (Rac-, L-, D-2-amino-1-propanol) as the templating cation, we have obtained (Rac-, L-, D-HTMPA)CdCl3 (HTMPA = 1-hydroxy-N, N, N-trimethyl-2-propanaminium). We have adopted a chiral chemistry strategy that causes (Rac-HTMPA)CdCl3 in the central symmetric space to crystallize in the chiral space group. Based on the modulation of the homochiral strategy, (L-, D-HTMPA)CdCl3 shows a dual phasic transition at 269 and 326 K and a switchable second-harmonic generation response. In addition, (L-, D-HTMPA)CdCl3 is chiral switchable material to exhibit stable dual dielectric and second-harmonic generation (SHG) switches. This work provides an approach to exploring multifunctional chiral switchable materials.

Interfacial Modulation of a Self-Sacrificial Synthesized SnO2@Sn Core-Shell Heterostructure Anode toward High-Capacity Reversible Li+ Storage.

Sn-based anodes are promising high-capacity anode materials for low-cost lithium ion batteries. Unfortunately, their development is generally restricted by rapid capacity fading resulting from large volume expansion and the corresponding structural failure of the solid electrolyte interphase (SEI) during the lithiation/delithiation process. Herein, heterostructural core-shell SnO2-layer-wrapped Sn nanoparticles embedded in a porous conductive nitrogen-doped carbon (SOWSH@PCNC) are proposed. In this design, the self-sacrificial Zn template from the precursors is used as the pore former, and the LiF-Li3N-rich SEI modulation layer is motivated to average uniform Li+ flux against local excessive lithiation. Meanwhile, both the chemically active nitrogen sites and the heterojunction interfaces within SnO2@Sn are implanted as electronic/ionic promoters to facilitate fast reaction kinetics. Consequently, the as-converted SOWSH@PCNC electrodes demonstrate a significantly boosted Li+ capacity of 961 mA h g-1 at 200 mA g-1 and excellent cycling stability with a low capacity decaying rate of 0.071% after 400 cycles at 500 mA g-1, suggesting their great promise as an anode material in high-performance lithium ion batteries.

Detection and genetic characterization of canine kobuvirus from stray dogs in Shanghai, China.

In this study, rectal samples collected from 60 stray dogs in dog shelters were screened for canine kobuvirus and other enteroviruses by quantitative real-time reverse transcription polymerase chain reaction. Canine kobuvirus was detected in 25% (15/60) of the samples. In the 15 positive samples, the coinfection rates of canine distemper virus, canine coronavirus, canine astrovirus, canine norovirus, and canine rotavirus were 26.67%, 20.00%, 73.33%, 0%, and 20.00%, respectively. Phylogenetic analysis based on partial VP1 sequences identified a novel canine kobuvirus that was a recombinant of canine and feline kobuvirus. Bayesian evolutionary analysis revealed that the rate of evolution of the VP1 gene of canine kobuvirus was 1.36 × 10-4 substitutions per site per year (95% highest posterior density interval, 6.28 × 10-7 - 4.30 × 10-4 substitutions per site per year). Finally, the divergence time of VP1 was around 19.44 years ago (95% highest posterior density interval, 12.96-27.57 years).

Inhibition of AGEs-RAGE-PP2A Axis Alleviates Cognitive Impairment after Chronic Heart Failure.

To investigate the effect of the AGEs-RAGE-PP2A axis on cognitive impairment (CI) after chronic heart failure (CHF). Mice were divided into six groups: Sham, TAC, Sham+RAGE-/-, TAC+RAGE-/-, AG, and FTY720 group. AG mice and FTY720 mice were treated with AGEs inhibitor (aminoguanidine, AG) and PP2A activator (FTY720) respectively after TAC surgery. The cardiac function of AG and TAC+RAGE-/- mice was significantly better than that of TAC mice (P<0.05). However, the heart function of FTY720 mice were just improved a part of that. To behavioral function, the escape latency period of the TAC+RAGE-/-, AG and FTY720 mice were significantly shorter (P<0.05), and the times of platform crossings and residence time of them were significantly improved (P<0.05). HE staining and silver staining show the structure of TAC+RAGE-/-, AG and FTY720 mice were more complete. Also, in these three groups, the expression of Aß and p-tau protein in the brain can be significantly down-regulated (P<0.05) and the PP2A protein expression level was up-regulated (P<0.05). And the expression of hippocampal Bax, Cyt-C, and Caspase-3 of that were all down-regulated (P<0.05), and Bcl-2 was up-regulated (P<0.05). Deficient of AGEs, RAGE and activating PP2A can significantly attenuate the cognitive impairment in CHF mice, and protect the brain structure. This mechanism seems via reducing the expression of Aß, p-tau, and apoptotic protein.