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Aim: Different nociceptive models induced with heat and chemicals were used to assess the potency of emodin in alleviating pain. The anti-inflammatory properties of emodin at different doses were also assessed using different anti-inflammatory in vivo models. Objective: Pain management is a global problem nowadays, and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to assuage inflammation and alleviate pain. Prolonged usage of these NSAIDs triggers various adverse drug reactions (ADRs). The dose-dependent effect of emodin was assessed by treating mice with three different doses (5, 10, and 20 mg/kg bwt) of emodin. Methods: The effects of emodin in various nociceptive and inflammatory models were assessed. The anti-nociceptive potential of emodin was evaluated with the hot plate and tail immersion tests. The effects of emodin on acetic acid-, glutamate-, capsaicin-, and formalin-stimulated pain models were examined. The anti-inflammatory potency of emodin was examined in a carrageenan-induced inflammatory model. The sedative effect of emodin was assessed by an open field test. Results: Emodin potentially prevented the nociception provoked by thermal stressors during the hot plate and tail immersion methods and from chemical stressors such as acetic acid, formalin, capsaicin, and glutamate. The anti-inflammatory action of emodin was evidenced by carrageenaninduced paw edema and peritoneal leukocyte penetration. The open field results confirmed that emodin induced a mild sedative effect on the treated mice. Conclusion: Our overall results obtained from this study confirmed that emodin exhibits potent anti- nociceptive and anti-inflammatory effects.

Establishing highly effective charge transfer channels in carbon nitride (g-C3N4) to enhance its photocatalytic activity is still a challenging issue. Herein, the delaminated 2D Ti3C2 MXene nanosheets were employed to decorate the P-doped tubular g-C3N4 (PTCN) for engineering 1D/2D Schottky heterojunction (PTCN/TC) through electrostatic self-assembly. The optimized PTCN/TC exhibited the highest hydrogen evolution rate (565 μmol/h/g), which was 4.3 and 2.0 -fold higher than pristine bulk g-C3N4 and PTCN, respectively. Such enhancement may be primarily attributed to the phosphorus heteroatom doped and unique structure of 1D/2D g-C3N4/Ti3C2 Schottky heterojunction, enhancing the light-harvesting and charges’ separation. One-dimensional pathway of g-C3N4 tube and built-in electric field of interfacial Schottky effect can significantly facilitate the spatial separation of photogenerated charge carriers, simultaneously inhibit their recombination via Schottky barrier. In this composite, metallic Ti3C2 was served as electrons sink and photons collector. Moreover, ultrathin Ti3C2 flake with exposed terminal metal sites as a co-catalyst exhibited higher photocatalytic reactivity in H2 evolution compared to carbon materials (such as reduced graphene oxide). This work not only proposed the mechanism of tubular g-C3N4/Ti3C2 Schottky junction in photocatalysis, but also provided a feasible way to load ultrathin Ti3C2 as a co-catalyst for designing highly efficient photocatalysts.

The physical and mechanical properties of graphene-reinforced epoxy (epoxy/graphene) in hygrothermal environment need to be comprehensively understood. This is because it is necessary to predict the durability of epoxy/graphene when epoxy/graphene is used in an aggressive environment with high humidity and high temperature. Based on the molecular dynamics method, the influences of water content (2, 4 and 6%) and temperature (298,333 and 368 K) on the physical and tensile properties of epoxy/graphene were studied in this research. The results showed that after the addition of graphene, the free volume fraction of epoxy and the diffusion coefficient of water molecules in the epoxy decreased, and the density, tensile strength and deformation performance of epoxy increased. In the hygrothermal environment, the tensile strength degradation rate of epoxy/graphene was lower than that of pure epoxy. The failure mechanism and mechanical response of epoxy/graphene during the tensile process in the nanoscale were revealed. The research results provide a reference for the design and performance optimization of epoxy/graphene composites in a hygrothermal environment.

Combining molecular transition-metal complexes and semiconductors is an effective way to create high-performance hybrid photocatalysts based on improvement of solar energy harvesting ability and photogenerated charge carrier separation efficiency.

Herein, based on the solvent-induced effect, we constructed the 3D flower-like Ni2P/CNTs hybrids. Profiting from the larger reaction active area and faster transport of ions/charges, it delivered the outperforming specific capacitance and cycling stability.

Although exopolysaccharide (EPS) has been applied to various fields, EPS for UVR-mediated oxidative stress repair still needs further exploration. In this study, a novel EPS was isolated from the fermentation medium of Bacillus sp. QDR3-1 and its yield was 4.8 g/L (pH 8.0, 12 % glucose, 30 °C and 6 % NaCl). The pure fraction (named EPS-M1) was purified by DEAE-cellulose and Sephadex G-100 column. EPS-M1 was a heteropolysaccharide composed of Man, Glc, Gal, and Fuc with a molecular weight of 33.8 kDa. Scanning electron microscopy (SEM) observed a rough surface and reticular structure of EPS-M1, and EPS-M1 formed spherical aggregates in aqueous solution observed in atomic force microscopy (AFM). Thermal analysis revealed that the degradation temperature of EPS-M1 was 306 °C. Moreover, methylation and NMR analysis determined that EPS-M1 was consisted of →3)-Manp-(1→, →2,6)-Manp-(1→, →4,6)-Glcp-(1→, →3)-Glcp-(1→, →4)-Galp-(1→, →4)-Fucp-(1→, and T-Manp-(1→. Furthermore, the cytotoxicity and the repair ability of UVR-mediated cell damage of EPS-M1 were studied with L929 cells. The results showed that EPS-M1 had good biocompatibility and it could mitigate UVR-mediated cell damage by regulating the levels of cellular reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (MMP) and Caspase-3/7 activity. Overall, the structure analysis and the protective effects of EPS against L929 cells exposed to UVR provided an experimental basis for EPS in practical applications.

Pancreatic intraductal pressure is related to the development of pancreatitis, including post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis. In this study, we investigate pancreatic intraductal pressure in various mouse models of acute and chronic pancreatitis.Post-ERCP pancreatitis was induced by retrograde infusion of normal saline or radiocontrast at the constant rate of 10 or 20 μL/min. Obstructive pancreatitis was induced by ligation of the pancreatic duct followed by a single injection of caerulein and the changes of intraductal pressure were recorded in day 3 for obstructive acute pancreatitis and day 14 for obstructive chronic pancreatitis. Non-obstructive pancreatitis was induced by repetitive intraperitoneal injections of caerulein. The changes of intraductal pressure were recorded right after the last caerulein injection for non-obstructive acute pancreatitis and after the completion of 4-week caerulein injections for non-obstructive chronic pancreatitis.Elevated pancreatic intraductal pressure was observed in both normal saline and radiocontrast infusion groups and was furtherly indicated that was positively correlated with the viscosity of solution but not genders. In the models of obstructive pancreatitis, a rise in intraductal pressure was observed in both acute and chronic pancreatitis; whereas in the models of non-obstructive pancreatitis, a rise in intraductal pressure was only observed in chronic, but not acute pancreatitis.During ERCP, the elevations in pancreatic intraductal pressure are induced by increasing rate or viscous solution of infusion. During different forms of experimental acute and chronic pancreatitis, obstructive or non-obstructive etiologies of pancreatitis also induces the elevations in pancreatic intraductal pressure.

Single-cell RNA sequencing (scRNA-seq) is one of the most efficient technologies for human tumor research. However, data analysis is still faced with technical challenges, especially the difficulty in efficiently and accurately discriminating cancer/normal cells in the scRNA-seq expression matrix. If we can address these challenges, we can have a deeper understanding of the intratumoral and intertumoral heterogeneity. In this study, we developed a cancer/normal cell discrimination pipeline called pan-Cancer Seeker (CaSee) devoted to scRNA-seq expression matrix, which is based on the traditional high-quality pan-cancer bulk sequencing data using transfer learning. CaSee is the first tool directly used to discriminate cancer/normal cells in the scRNA-seq expression matrix, with much wider application fields and higher efficiency than copy number variation (CNV) method which requires corresponding reference cells. CaSee is user-friendly and can adapt to a variety of data sources, including but not limited to scRNA tissue sequencing data, scRNA cell line sequencing data, scRNA xenograft cell sequencing data and scRNA circulating tumor cell sequencing data. It is compatible with mainstream sequencing technology platforms, 10× Genomics Chromium, Smart-seq2, and Microwell-seq. Here, CaSee pipeline exhibited excellent performance in the multicenter data evaluation of 11 retrospective cohorts and one independent dataset, with an average discrimination accuracy of 96.69%. In general, the development of a deep-learning based, pan-cancer cell discrimination model, CaSee, to distinguish cancer cells from normal cells will be compelling to researchers working in the genomics, cancer, and single-cell fields.

The handheld micro tiller is a typical small agricultural machine. It vibrates severely during the rotary tillage process, which harms the users’ health. It is necessary to study its vibration characteristics and propose vibration isolation measurements. Firstly, the external forces applied on various components of the micro-tiller were analyzed. The main components of the handheld micro tiller were simplified. And then the micro-tiller vibration model was built. The time-frequency domain characteristics of the micro-tiller were analyzed. The main components’ RMS values were calculated. It shows that the excitation force of the engine is the main source of vibration of the micro-tiller. The simulated RMS values of the frame and the gearbox were compared to the tested values. The errors indicate the established model is to some extent reasonable. In order to reduce the vibration transmitted to the handrail, firstly, the ordinary bolts connecting the engine and the frame were replaced with rubber bolts. And then the RMS value was analyzed and calculated. The results showed that this method could not effectively reduce the vibration of other main components. Furthermore, it is considered to install a vibration isolator between the engine and the frame of the tiller. Time-frequency domain simulation results show that after adding the vibration isolator, the vibration RMS value of each component was much smaller than before. It shows that it isolates the engine vibration effectively. The research in this paper laid the foundation for designing a reasonable vibration isolator and reducing the vibration of the main components of the tiller.

Apoptosis of kidney tubular epithelial cells contributes to diabetic kidney disease (DKD) pathophysiology, but the mechanisms are not fully understood. Zinc transporter protein member 8 (ZnT8, SLC30A8) is a susceptive gene in diabetes. Here, we aim to investigate whether ZnT8 has effects on pathophysiology of DKD. The animal groups include control, ZnT8KO mice, STZ-induced, and ZnT8-KO-STZ. STZ-induced DKD was performed in male C57BL/6 J mice and in ZnT8-KO mice. High glucose (HG)-induced apoptosis in a normal rat kidney tubular epithelial cell line (NRK-52E cells) was performed in vitro. Transfection of hZnT8-EGFP or TNFAIP3 siRNA was done in NRK-52E cells. Flow cytometry with Annexin V-FITC/PI double staining and TUNEL analysis was performed for the detection of apoptosis. Gene expression at mRNA and protein levels was examined with real-time RT-PCR and Western blot. Urine albumin to creatinine ratio, proinflammatory cytokines, and apoptosis were enhanced in kidneys of STZ and ZnT8-KO-STZ mice compared to control or ZnT8-KO mice. ZnT8 overexpression after hZnT8-EGFP transfection decreased HG-stimulated inflammatory activity and apoptosis in NRK-52E cells. Furthermore, treatment with ZnSO

Our study aimed to examine the effects of COVID-19 on the physical fitness and academic performance of Chinese college students.The sample included physical fitness test data from 9,712 undergraduate students and academic performance data from 12,000 undergraduate students at a top university in China.Physical fitness was measured and evaluated according to the Chinese National Student Physical Fitness Standard. Data were analyzed using two-sample t-tests and Pearson product-moment correlations.Total physical fitness test scores of college students decreased after the outbreak, but their mean body mass index (BMI) remained at normal levels. The mean academic performance of college students unexpectedly improved during the online learning period. The positive correlation between physical test scores and academic performance was significantly higher during COVID-19 than that before the outbreak.Chinese college students with high physical fitness during COVID-19 were more likely to achieve good academic performance.

Confined liquid has attracted great attention due to its potential applications in nanofluidic devices. With the development of liquid-cell transmission electron microscopy (LC-TEM), investigating the behaviors of confined liquid can be realized in real time. However, the dynamics of the liquid layer in liquid cells have not been fully understood. Here, nanoparticles (NPs) adhered to the cell window membranes are used as reference objects to study the flow regime of the liquid layer, which causes cooperative motion of the membranes and the NPs. Two categories of motion behaviors are investigated. One is the contraction of NPs toward the interior viewing area which results from the spreading out of the liquid to the surrounding region, with the bending of the membranes increasing with the loss of liquid in the viewing area. The other motion behavior is the occasional movement of all the NPs in the same direction with the directional movement of the liquid layer. This work offers a new method to study the dynamics of liquids by LC-TEM, the discoveries of which are valuable for understanding the confined liquid dynamics.

Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC. KP2 was treated with oxaliplatin and olaparib (OXPARPi), and a resistant cell line was subsequently cloned to generate multiple genetically distinct cell lines (KP2-OXPARPi clones). Clones A and E are sensitive to immune checkpoint inhibition (ICI), exhibit relatively high T cell infiltration, and have significant upregulation of genes involved in antigen presentation, T cell differentiation, and chemokine signaling pathways. Clone B is resistant to ICI and is similar to the parental KP2 cell line in terms of relatively low T cell infiltration and no upregulation of genes involved in the pathways noted above. Tumor/normal exome sequencing and in silico neoantigen prediction confirms successful generation of cancer neoantigens in the KP2-OXPARPi clones and the relative lack of cancer neoantigens in the parental KP2 cell line. Neoantigen vaccine experiments demonstrate that a subset of candidate neoantigens are immunogenic and neoantigen synthetic long peptide vaccines can restrain Clone E tumor growth. Compared to existing models, the KP2-OXPARPi clones better capture the diverse immunobiology of human PDAC and may serve as models for future investigations in cancer immunotherapies and strategies targeting cancer neoantigens in PDAC.

Background: It is now widely acknowledged that the adaptive evolutionary process of cancer cells is characterized by genomic and epigenetic alterations. Nevertheless, the extreme heterogeneity of cancer cells and the extreme sparsity of scRNA-seq data limited the understanding of cancer cell reconfiguration of anomaly pathway activity and adaptive evolution under selection pressure. Methods: We collected a total of 7,955 tumor samples, including 32 common human cancer types as the training set. Five sets of scRNA-seq data from different studies covering 5 different cancer types were used as the validation set. Results: In this study, we used a contrastive learning approach to analyze scRNA-seq data and developed a sceAPA model to determine the spatial mapping correlation between RNA features and genomic variation-associated anomaly pathway activities in cancer. The dynamic transcriptional profile revealed by scRNA-seq reflects how cancer cells reconfigure their transcriptome pattern and develop various APA patterns in response to selective pressure to gain an evolutionary advantage. We found that the plasticity of human cancer was negatively related to the transcriptome burden, and increasing transcriptome burden was associated with more chaotic APA patterns. Conclusions: Our study shows that cancer cells possess greater plasticity by reprogramming immune-associated transcript patterns, thereby conferring greater resistance to selection pressure. The plasticity of cancer cells is closely related to adaptive evolution, drug resistance, distant metastasis, and immune escape.

The spread of polymyxin-resistant Enterobacteriaceae poses a significant threat to public health and challenges the therapeutic options for treating infections on a global level. In this study, mcr-1 -bearing ST10 E. coli was isolated from pigs, pork, and humans simultaneously, which demonstrated that ST10 E. coli was an important vehicle for the spread of mcr-1 among animals, foods, and humans.

Characterization of tier 1 mutations identified in WHIM37 through NSG.

Characterization of tier 1 mutations identified in WHIM35 through NSG.

Characterization of tier 1 mutations identified in WHIM30 through NSG.

Next-generation sequencing technologies have provided insights into the biology and mutational landscape of cancer. Here, we evaluate the relevance of cancer neoantigens in human breast cancers. Using patient-derived xenografts from three patients with advanced breast cancer (xenografts were designated as WHIM30, WHIM35, and WHIM37), we sequenced exomes of tumor and patient-matched normal cells. We identified 2,091 (WHIM30), 354 (WHIM35), and 235 (WHIM37) nonsynonymous somatic mutations. A computational analysis identified and prioritized HLA class I–restricted candidate neoantigens expressed in the dominant tumor clone. Each candidate neoantigen was evaluated using peptide-binding assays, T-cell cultures that measure the ability of CD8+ T cells to recognize candidate neoantigens, and preclinical models in which we measured antitumor immunity. Our results demonstrate that breast cancer neoantigens can be recognized by the immune system, and that human CD8+ T cells enriched for prioritized breast cancer neoantigens were able to protect mice from tumor challenge with autologous patient-derived xenografts. We conclude that next-generation sequencing and epitope-prediction strategies can identify and prioritize candidate neoantigens for immune targeting in breast cancer. Cancer Immunol Res; 5(7); 516–23. ©2017 AACR.

Supplementary Figure 1. H&E of WHIM30, WHIM35 and WHIM37 parental tumors. Supplementary Figure 2. Peptides corresponding to prioritized neoantigens can induce strong surface expression of HLA class I molecules. Supplementary Figure 3. Indirect tumor-specific immune response. Supplementary Figure 4. The immune response to neoantigens is HLA-specific. Supplementary Figure 5. Prioritized neoantigens induce immune responses in HLA-A0201 transgenic. Supplementary Table 1. Patient clinical characteristics. Supplementary Table 5. Summary of candidate neoantigens identified by exome sequencing. Supplementary Table 6. HLA typing. Supplementary Table 7. Candidate neoantigens and HLA class I predicted binding affinities for WHIM30. Supplementary Table 8. Candidate neoantigens and HLA class I predicted binding affinities for WHIM35.

Considering the structural complexity of natural bone and the limitations of current treatment options, designing a biomimetic and functional tissue-engineered bone graft has been an urgent need for the replacement and regeneration of defected bone tissue. In light of the cell recruitment to the defect region, scaffold-guided bone tissue engineering has proven to be a viable strategy that is poised to deliver effective osseointegration and vascularization during bone remodeling. Herein, we provide an engineered bone scaffold based on aligned poly(lactic-co-glycolide) (PLGA) nanofibers incorporated with hyaluronic acid oligosaccharide-collagen mineralized microparticles (labeled oHA-Col/HAP) to guide the cell-specific orientation and osseointegration in bone healing. The aligned nanofibers were successfully prepared by a custom-made rotating mandrel with separating railings and HAs-Col/HAP mineralized microparticles were uniformly distributed in the composite scaffolds that acted as temporary templates for bone remodeling. The morphology, physicochemical properties and tensile strength of the scaffolds were characterized, the cell responses and in vivo biocompatibility and biodegradability of the scaffolds were also studied to evaluate the potential for bone tissue engineering. The experimental results illustrated that such anisotropic scaffolds loaded with oHA-Col/HAP microparticles mediated cell orderly arrangement conducive to the migration and recruitment of osseointegration-related cells and were stimulatory of cell proliferation. Those oHA-Col/HAP@PLGA scaffolds exhibited ideal biocompatibility and tissue regenerative capacity in vivo through a higher expression of vascularization-related genes. Overall, the novel engineered bone scaffold promises to serve as alternative candidates for bone tissue engineering applications.

The uncontrolled deposition/dissolution process of lithium dendrites during electrochemical cycling in batteries limits the large-scale application of Li metal anodes. Investigating the microstructure of Li dendrites is a focal point. Currently, the only way to protect and observe sensitive Li dendrites is through low-temperature transmission electron microscopy (LT-TEM), whereas room-temperature characterization is still lacking. In this work, the room-temperature microstructure of Li dendrites was obtained by TEM using both vacuum- and inert-gas-transfer methods. Detailed comparison between LT- and room-temperature (RT-)TEM characterizations was provided to show the pros and cons of each method. Especially, RT-TEM shows the advantage of flexible incorporation with multifunctional characterizations, such as 3D tomography. By using RT-TEM, microstructural evolution of Li dendrites during the electrodeposition/dissolution process, including increase of the quantity of inorganic Li

A novel and convenient method for the highly chemoselective synthesis of β-hydroxysulfides mediated by DMSO is reported. This eco-friendly reaction was amenable to a broad range of substrates and provided the desired β-hydroxysulfides in moderate to good yields with high selectivity via radical process. Moreover, several pharmaceutical and bioactive molecules were also suitable substrates for this reaction conditions to afford the targeted products in good yields.

Waste Activated Carbon (WAC), as a typical solid waste, can be utilized by Chemical-Looping Gasification (CLG) technology with an iron-based Oxygen Carrier (OC) to produce valuable synthesis gas. A series of experiments on WAC of the CLG process has been performed in a fixed-bed reactor. The operation parameters and cyclic performance of the iron-based OC have been investigated during CLG reactions. Fresh and cyclic reaction OC samples have been analyzed by X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). To obtain high-quality syngas with high carbon conversion, the optimal OC/WAC mole ratio, steam flow rate and reaction temperature are 0.1, 0.10 mL/min, and 950 °C, respectively. The iron-based OC exhibits a stable cyclic performance during multiple tests, following the reaction path of Fe2O3 to Fe0.98O in the individual reduction process. Moreover, the iron-based OC is oxidized to almost its initial state after 10 redox tests without obvious sintering and agglomeration phenomena. The WAC of CLG provides a new approach to the comprehensive usage of solid waste, especially with low volatile feedstock.

The combination of in situ TEM and theoretical analysis is applied to further analyze the behavior of nanoparticles in flocculation; particularly, for the in situ noninvasive probing of effect substances after cupping.

Bismuth oxyiodide and attapulgite have proven to be potential materials for the removal of emerging contaminants in wastewater. In this work, bismuth oxyiodide/attapulgite (BIA-x) composites with various amounts of attapulgite were readily synthesized by mechanical grinding in ta mortar at room temperature. The chemical bonds, specific surface area, and morphology of resulting materials were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, surface area, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, and transmission electron microscopy. In the photodegradation process, BIA-8 exhibits the best performance for both rhodamine B (96.3% removal in 40 min, 4.22-fold as BiOI) and tetracycline (85.2% removal in 40 min, 1.67-fold as BiOI) removal. Furthermore, photoelectrochemical and radical trapping experiments were performed to study the mechanisms of photodegradation. Based on the experimental results, holes, and superoxide radicals were the main active species during the photodegradation possess. The hydroxyl radicals were not adequate to acquire due to the low valence band position. The photodegradation capacity increased after attapulgite was added, which might be due to the synergism of bismuth oxyiodide and attapulgite.

GDYO/PVA self-assembled composite membrane as a separator effectively inhibited the self-discharge of AEESCs. The ultra-long self-discharge time is 37 160 s, and the capacitance retention rate is 95.1% after 8000 cycles.

The eukaryotic chaperonin family is vital for cell survival. The dysregulation of chaperonin-containing TCP-1 subunit 3 (CCT3) is implicated in several types of malignant tumors' development. However, its functional role in melanoma remains unknown. Here we elucidate the functional contribution to CCT3 to melanoma progression. The results indicated that CCT3 highly expressed in melanoma tissues, and CCT3 overexpression is correlated with clinical stage in melanoma patients. Knockdown of CCT3 by shRNA in melanoma cells inhibited cell proliferation and cell cycle progression and induced cell apoptosis

Quercetin exerts antihypertensive effects, while its role on hypertensive renal injury remain unknown. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2 and BaX) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Hematoxylin and eosin staining revealed that quercetin treatment reduced the pathological changes in renal tissues of Ang II infused mice. RNA sequencing identified quercetin treatment significantly reversed 464 DETs and enriched several signaling pathway (including apoptosis and p53 pathways). Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling staining and Annexin V staining revealed that quercetin treatment reduced cell apoptosis in renal tissues of Ang II-infused mice and in NRK-52E cells stimulated with Ang II. Furthermore, immunohistochemistry and western-blotting indicated that quercetin treatment alleviated the upregulation of p53, BaX, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II infused mice and NRK-52E cells stimulated with Ang II stimulation. Moreover, the molecular docking results indicated potential binding activity between quercetin-TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-induced mice and Ang II stimulated NERK-52E cell, and by targeting p53 may be one of the underlying mechanisms.

Background: Diabetic retinopathy (DR) is the main reason of visual impairment. Apigenin has anti-angiogenic effects in a variety of diseases. Our aim was to explore the role of apigenin in DR and the mechanism involved. Methods: High glucose (HG) induced HRMEC to establish DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. miR-140-5p, HDAC3 and PTEN were detected by qRT-PCR. Western blot measured HDAC3, PTEN and PI3K/AKT pathway related proteins expressions. Cell proliferation and migration were monitored by MTT, wound-healing assay and Transwell assay. Angiogenesis was detected by Tube formation assay. Results: After HG treatment, miR-140-5p expression was repressed and miR-140-5p overexpression suppressed HG-induced HRMECs proliferation, migration and angiogenesis. Apigenin treatment significantly reversed the reduction in miR-140-5p level caused by HG treatment and repressed HG-induced HRMECs proliferation, migration and angiogenesis by elevating miR-140-5p. miR-140-5p targeted HDAC3, and overexpression of miR-140-5p could reverse the up-regulation of HDAC3 expression induced by HG treatment. HDAC3 could bind to the promoter region of PTEN and inhibit its expression, and then knocking down HDAC3 suppressed PI3K/AKT pathway via elevating PTEN level. In addition, apigenin inhibited angiogenesis in DR cell models by regulating miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Conclusions: Apigenin inhibited angiogenesis of HG induced HRMECs by regulating miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study might provide new drugs and new targets for treating DR.

Gastrodin has been used as antihypertension therapy in China; however, the mechanisms underlying the effects of gastrodin have yet to be fully elucidated. To explore the therapeutic efficiency of gastrodin as an antihypertensive and determine the mechanisms underlying this effect. C57BL/6 mice were continuously administered angiotensin II (Ang II) (500 ng/kg/min) to induce hypertension. Mice were randomly divided into control, Ang II and Ang II + gastrodin groups. Mice received intragastric administration of gastrodin (5 mg/kg) or double distilled water once a day for 4 weeks. Blood pressure, pulse wave velocity (PWV), thickness of the abdominal aorta, pathological morphology and differential expression transcripts (DETs) were assessed. Abdominal aorta rings and primary isolated vascular smooth muscle cells were subjected to Ang II stimulation to induce hypertension as ex vivo and in vitro models, respectively. Vascular ring tension, release of Ca2+ and levels of proteins involved in the myosin light chain kinase (MLCK)/phospho-myosin light chain 2 (p-MLC2) pathway were determined. Gastrodin treatment attenuated increases in blood pressure, PWV and thickness of the abdominal aorta. Treatment with gastrodin resulted in 2785 DETs and the enrichment of vascular contraction and calcium signalling pathways. Gastrodin treatment attenuated Ang II-induced vasoconstriction, produced a norepinephrine-precontracted vasodilation effect (attenuated by verapamil), and reduced intracellular Ca2+ release. Furthermore, gastrodin suppressed activation of the MLCK/p-MLC2 pathway in vivo and in vitro. Gastrodin treatment lowers blood pressure, suppresses Ang II-induced vascular contraction and MLCK/p-MLC2 pathway activation, thereby demonstrating the mechanisms underlying the therapeutic efficacy of gastrodin as an antihypertensive.

This work studies the distribution of warehouses and distribution centers (W&DCs) in California and analyzes their potential relationships with disadvantaged communities (DACs). Through aggregated spatial analyses and econometric modeling, the research compares the concentration of W&DCs in five metropolitan planning organizations (MPOs) in California. The analyses show that the weighted geometric centers of W&DCs have shifted slightly toward city central areas in all five MPOs in the last few years, contrasting to the logistics sprawl trends evidenced in previous research. In the Bay Area and Southern California, W&DCs are more prevalent in areas with higher pollution burden, according to the CalEnviroScreen (CS) score. In Southern California, the study analyzes disaggregate industrial real estate data of 49,697 property transactions (properties sold) between 1989 and 2018. On average, the size of the facilities transacted have decreased, especially for those closer to the urban center. These results are confirmed using parametric and non-parametric data analyses. During recent years, smaller and closer (to the urban core) facilities represent the largest share in the transactions, consistent with the trends in e-commerce and its associated distribution requirements. Moreover, the data show a disproportionate sitting of facilities in areas where DACs reside. The paper ends with a discussion of policy and planning recommendations.

BackgroundTaijiquan, as a physical and mental exercise, can improve the negative psychology of college students. However, it is still controversial, and the optimal exercise dose of taijiquan to interfere with negative psychology has not been evaluated.ObjectiveThis study is aimed at systematically evaluating the effect of taijiquan therapy on improving negative psychological symptoms of college students and its optimal intervention dose.MethodsSearch databases such as Web of Science, Embase, PubMed, CNKI, WFSD, etc. Collect high-quality relevant RCT studies. After screening, extracting, coding and counting the data, a META analysis is done through Review Manage 5.3 and Stata 15.0 software. PICOS established the eligibility criteria to select the studies as follows: (i) population - non-clinical of college students; (ii) intervention - taijiquan intervention; (iii) comparison - taijiquan intervention group and regular physical activity group; (iv) outcomes - depression, anxiety; and (v) study design - randomized controlled trial.ResultsA total of 12 articles and 1,000 samples were included. All of the participants are college students. Taijiquan therapy can significantly reduce the depression and anxiety symptoms of college students [SMD = −0.53, 95% CI (−0.82, −0.23)], [SMD = −0.49, 95% CI (−0.90, −0.09)], with statistical significance (P < 0.05). Subgroup analysis shows that: there is a precise focus on depression and anxiety symptoms. The intervention period is more than 12 weeks, and the best effect appears when people practice 3 times a week. The best single intervention time for depression symptoms is 60 min, and for anxiety symptoms 80–90 min. It is found that taijiquan combined with mindfulness intervention can significantly reduce negative psychological symptoms like depression and anxiety of college students than single taijiquan intervention. Funnel plot combined with sensitivity analysis, Begg, Egger test showed no publication bias.ConclusionTaijiquan intervention can effectively improve the negative psychological symptoms of college students, and it has great promotion value in colleges and universities.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022314071.

BackgroundCancer neoantigens are important targets of cancer immunotherapy and neoantigen vaccines are currently in development in pancreatic ductal adenocarcinoma (PDAC) and other cancer types. Immune regulatory mechanisms in pancreatic cancer may limit the efficacy of neoantigen vaccines. Targeting immune checkpoint signaling pathways in PDAC may improve the efficacy of neoantigen vaccines.MethodsWe used KPC4580P, an established model of PDAC, to test whether neoantigen vaccines can generate therapeutic efficacy against PDAC. We focused on two immunogenic neoantigens associated with genetic alterations in the CAR12 and CDK12 genes. We tested a neoantigen vaccine comprised of two 20-mer synthetic long peptides and poly IC, a Toll-like receptor (TLR) agonist. We investigated the ability of neoantigen vaccine alone, or in combination with PD-1 and TIGIT signaling blockade to impact tumor growth. We also assessed the impact of TIGIT signaling on T cell responses in human PDAC.ResultsNeoantigen vaccines induce neoantigen-specific T cell responses in tumor-bearing mice and slow KPC4580P tumor growth. However, KPC4580P tumors express high levels of PD-L1 and the TIGIT ligand, CD155. A subset of neoantigen-specific T cells in KPC4580P tumors are dysfunctional, and express high levels of TIGIT. PD-1 and TIGIT signaling blockade in vivo reverses T cell dysfunction and enhances neoantigen vaccine-induced T cell responses and tumor regression. In human translational studies, TIGIT signaling blockade in vitro enhances neoantigen-specific T cell function following vaccination.ConclusionsTaken together, preclinical and human translational studies support testing neoantigen vaccines in combination with therapies targeting the PD-1 and TIGIT signaling pathways in patients with PDAC.

Vascular calcification is highly prevalent in chronic kidney disease (CKD), and is characterized by transdifferentiation from contractile vascular smooth muscle cells (VSMCs) into an osteogenic phenotype. However, no effective and therapeutic option to prevent vascular calcification is yet available. Dihydromyricetin (DMY), a bioactive flavonoid isolated from Ampelopsis grossedentata, has been found to inhibit VSMCs proliferation and the injury-induced neointimal formation. However, whether DMY has an effect on osteogenic differentiation of VSMCs and vascular calcification is still unclear. In the present study, we sought to investigate the effect of DMY on vascular calcification in CKD and the underlying mechanism. DMY treatment significantly attenuated calcium/phosphate-induced calcification of rat and human VSMCs in a dose-dependent manner, as shown by Alizarin Red S staining and calcium content assay, associated with down-regulation of osteogenic markers including type I collagen (COL I), Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2) and osteocalcin (OCN). These results were further confirmed in aortic rings ex vivo. Moreover, DMY ameliorated vascular calcification in rats with CKD. Additionally, we found that AKT signaling was activated during vascular calcification, whereas significantly inhibited by DMY administration. DMY treatment significantly reversed AKT activator-induced vascular calcification. Furthermore, inhibition of AKT signaling efficiently attenuated calcification, which was similar to that after treatment with DMY alone, and DMY had a better inhibitory effect on calcification as compared with AKT inhibitor. The present study demonstrated that DMY has a potent inhibitory role in vascular calcification partially by inhibiting AKT activation, suggesting that DMY may act as a promising therapeutic candidate for patients suffering from vascular calcification.

Under high-temperature batch fluidized bed conditions and by employing Juye coal as the raw material, the present study determined the effects of the bed material, temperature, OC/C ratio, steam flow and oxygen carrier cycle on the chemical looping combustion of coal. In addition, the variations taking place in the surface functional groups of coal under different reaction times were investigated, and the variations achieved by the gas released under the pyrolysis and combustion of Juye coal were analyzed. As revealed from the results, the carbon conversion ratio and rate were elevated significantly, and the volume fraction of the outlet CO2 remained more than 92% under the oxygen carriers. The optimized reaction conditions to achieve the chemical looping combustion of Juye coal consisted of a temperature of 900 °C, an OC/C ratio of 2, as well as a steam flow rate of 0.5 g·min−1. When the coal was undergoing the chemical looping combustion, volatiles primarily originated from the pyrolysis of aliphatic CH3 and CH2, and CO and H2 were largely generated from the gasification of aromatic carbon. In the CLC process, H2O and CO2 began to separate out at 270 °C, CH4 and tar began to precipitate at 370 °C, and the amount of CO2 was continuously elevated with the rise of the temperature.

Metastasis is the major cause of death and failure of cancer chemotherapy in patients with breast cancer (BC). Activation of TGF-β/lncRNA-MALAT1/miR-200c has been reported to play an essential role during the metastasis of BC cells. The present study aimed to validate the suppression of BC-cell migration and invasion by baicalin and explore its regulatory effects on the TGF-β/lncRNA-MALAT1/miR-200c signaling pathway. We found that baicalin treatment inhibited cell viability and migration and invasion. Mechanistically, baicalin treatment significantly downregulated the expression of TGF-β, ZEB1, and N-cadherin and upregulated E-cadherin on both mRNA and protein levels. Additionally, baicalin treatment significantly downregulated the expression of lncRNA-MALAT1 and upregulated that of miR-200c. Collectively, baicalin significantly suppresses cell viability, migration, and invasion of BC cells possibly by regulating the TGF-β/lncRNA-MALAT1/miR-200c pathway.