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Lycorine-nanoparticles (LYC-NPs) were successfully synthesized using anti-solvent precipitation-freeze drying method, and characterized using transmission electron microscopy (TEM), particle size analysis and Fourier transform infrared spectroscopy (FTIR). Then, the antitumor effects of LYC-NPs against HepG2 cells were investigated, and the underlying molecular mechanisms were explored. Our results showed that LYC-NPs displayed potent antiproliferative against HepG2 cells concentration dependently. Flow cytometry analysis exhibited that LYC-NPs triggered apoptosis and impeded cell cycle in G0/G1 phase. Moreover, the up-regulated expression of cleaved caspases-3 and Bax, and decrease of mitochondrial membrane potential and the Bcl-2 expression were involved in LYC-NPs apoptosis, implying that LYC-NPs induced apoptosis via the mitochondrial-mediated apoptosis pathway. Furthermore, LYC-NPs distinctly impaired HepG2 cells migration and invasion with down-regulation of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. These results indicated that LYC-NPs could be an favorable agent for restraining the growth and metastasis of HepG2 cells.

Pancreatic cancer is one of the most common causes of cancer death in the world due to the lack of early symptoms, metastasis occurrence and chemoresistance. Therefore, early diagnosis by detection of biomarkers, blockade of metastasis, and overcoming chemoresistance are the effective strategies to improve the survival of pancreatic cancer patients. Accumulating evidence has revealed that long noncoding RNA (lncRNA) and circular RNAs (circRNAs) play essential roles in modulating chemosensitivity in pancreatic cancer. In this review article, we will summarize the role of lncRNAs in drug resistance of pancreatic cancer cells, including HOTTIP, HOTAIR, PVT1, linc-ROR, GAS5, UCA1, DYNC2H1-4, MEG3, TUG1, HOST2, HCP5, SLC7A11-AS1 and CASC2. We also highlight the function of circRNAs, such as circHIPK3 and circ_0000284, in regulation of drug sensitivity of pancreatic cancer cells. Moreover, we describe a number of compounds, including curcumin, genistein, resveratrol, quercetin, and salinomycin, which may modulate the expression of lncRNAs and enhance chemosensitivity in pancreatic cancers. Therefore, targeting specific lncRNAs and cicrRNAs could contribute to reverse chemoresistance of pancreatic cancer cells. We hope this review might stimulate the studies of lncRNAs and cicrRNAs, and develop the new therapeutic strategy via modulating these noncoding RNAs to promote chemosensitivity of pancreatic cancer cells.

Waste honeycomb derived porous carbon with a high specific surface area of 1683.6 m2 g−1 are prepared via a facile simultaneous activation/carbonization. The corresponding porous carbon/sulfur composite cathode exhibits a durable stable performance up to 500 cycles at 1 C.

Lithium-sulfur batteries are expected to be prospective candidates of high-energy-storage systems due to their high theoretical specific capacity. However, poor electrical conductivity, severe polysulfide shuttle effect and low sulfur utilization generally cause inferior electrochemical performance, hence hindering the practical development. In this study, common makeup cotton derived self-supporting porous carbon fibers (SPCFs) are prepared by a facile simultaneous activation/pyrolysis process accompanied by the effectively regulation of a KHCO

Glioma is the most common brain cancer with a poor prognosis, and its underlying molecular mechanisms still needs to be further explored. In the current study, we discovered that an antisense lncRNA, CACNA1C-AS2, suppressed growth, migration and invasion of glioma cells, suggesting that CACNA1C-AS2 functions as a tumor suppressor. Furthermore, we found that CACNA1C-AS2 negatively regulated Fbxo45 protein expression in glioma cells. Impressively, extensive experimental results revealed that Fbxo45 accelerated growth, migration and invasion of glioma cells. Clinically, increased Fbxo45 expression was observed in 75 human glioma tissue samples. Moreover, in vivo experiments also demonstrated that Fbxo45 overexpression enhanced tumor growth in mice. Especially, we further identified that Fbxo45 activated mTORC1 rather than mTORC2 through PI3K/AKT signaling to promote cell growth and motility in glioma cells. Rescue experiments also exhibited that CACNA1C-AS2 inhibited cell growth and motility partly through down-regulating Fbxo45 expression in glioma. Our results provide the novel insights into the critical role of CACNA1C-AS2/Fbxo45/mTOR axis involved in regulating glioma tumorigenesis and progression, and further indicate that CACNA1C-AS2 and Fbxo45 may be the potential biomarkers and therapeutic targets for glioma.

Zhiguo Zhong,1 Yuyun Li,2,3 Yan Chen,2,3 Wen Chen,2 Siyan Li,4 Xiaohua Lv,2 Shiying Luo2 1Traditional Chinese Medicine Department, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524023, People’s Republic of China; 2Department of Pharmacology, School of Pharmacy, Guangdong Key Laboratory for Research and Development of Natural Drugs, Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, 524023, People’s Republic of China; 3Institute of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical University, Dongguan, 523808, People’s Republic of China; 4School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of ChinaCorrespondence: Shiying LuoDepartment of Pharmacology, School of Pharmacy, Guangdong Key Laboratory for Research and Development of Natural Drugs, Marine Biomedical Research Institute, Guangdong Medical University, No. 2 East Wenming Road, Xiashan District, Zhanjiang, 524023, Guangdong, People’s Republic of ChinaTel +86 13763058766Fax +86 7592388588Email luosy76@gdmu.edu.cnBackground: Erzhi Pill (EZP), a traditional Chinese medicine (TCM) prescription, has been widely applied to improve bone metabolism and treat osteoporosis (OP) in China. However, its effective constituents and mechanisms remain unclear.Methods: By combining network pharmacology and zebrafish experiments, an integrative method was employed to address this problem. Firstly, the disease targets of OP were collected from two public gene databases. Secondly, the active compounds and drug targets of EZP were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). Thirdly, a drug-target-disease interaction network was constructed, and the key active components were identified by analyzing the topological characteristics of the network. Finally, these predicted results were tested by zebrafish experiments and compared with those from the literature. Specifically, quercetin as an important representative active component of EZP was applied to wild type and transgenic zebrafish larvae to assess its effects on skull mineralization and osteoplastic differentiation.Results: Our study identified 72 active compounds, 220 targets and 166 signaling pathways probably involved in the prevention and treatment of OP by EZP, wherein quercetin, apigenin, daidzein, luteolin, ursolic acid and kaempferol could be the key compounds, while PI3K-Akt signaling pathway, TNF signaling pathway and IL-17 signaling pathway could be the key signaling pathways. The experiments indicated that quercetin attenuated both the decrease of skull mineralization and the inhibition of skull osteoplastic differentiation in zebrafish larvae trigged by dexamethasone.Conclusion: Our study not only investigated potentially effective constituents and mechanisms of EZP in the prevention and treatment of OP, but also provided a reference for the in-depth research, development and application of TCM.Keywords: Erzhi Pill, osteoporosis, network pharmacology, mechanisms, zebrafish, quercetin

To describle how respiratory tract infections (RTIs) that occurred in children with allergic asthma (AA) on allergen immunotherapy (AIT) during an influenza season. Data including clinical symptoms and treatment history of children (those with AA on AIT and their siblings under 14 years old), who suffered from RTIs during an influenza season (Dec 1st, 2019–Dec 31st, 2019), were collected (by face to face interview and medical records) and analyzed. Children on AIT were divided into 2 groups: stage 1 (dose increasing stage) and stage 2 (dose maintenance stage). Their siblings were enrolled as control. During the study period, 49 children with AA on AIT (33 patients in stage 1 and 16 patients in stage 2) as well as 49 children without AA ( their siblings ) were included. There were no significant differences in occurrences of RTIs among the three groups (p > 0.05). Compared with children in the other two groups, patients with RTIs in stage 2 had less duration of coughing and needed less medicine. Children on AIT with maintenance doses had fewer symptoms and recovered quickly when they were attacked by RTIs, which suggested that AIT with dose maintenance may enhance disease resistance of the body.

Chemotherapeutic strategy has been widely used for treating malignance by targeting irregular expressed or mutant proteins with small molecular inhibitors (SMIs) or monoclonal antibodies (mAbs). However, most intracellular proteins lack of active sites or antigens where SMIs or mAbs bind with, and are called as non-druggable targets for a long time. From the first year of this century, PROteolysis-TArgeting Chimeras (PROTACs) has emerged to be a promising approach for proteins, including those non-druggable ones, such as transcriptional factors and scaffold proteins. The first generation of peptide-based PROTACs adopts β-TrCP and VHL as E3 ligases, but the cellular permeability and chemical stability issues restrict their clinical application. The second generation of small molecule-based PROTACs adopts MDM2, VHL, IAPs and Cereblon as E3 ligases have been tensely studied. To date, the targets of PROTACs including those overexpressed oncogenic proteins such as ER, AR and BRDs, disease-relevant fusion proteins such as NPM/EML4-ALK and BCR-ABL, cancer-driven mutant proteins such as EGFR, kinases such as CDKs and RTKs. The major disadvantage of PROTACs is the noncancer specificity and relative higher toxicity, due to its catalytic role. To overcome this, we and other have recently developed several similar light-controllable PROTACs, termed as the third generation controllable PROTACs. The degradation of targets by those PROTACs can be triggered by UVA or visible light, providing a tool box for further PROTACs design. Here in this review, we introduce the historical milestones and prospective for further PROTACs development in clinical use.

Glucocorticoid-induced osteoporosis (GIOP) that is mainly featured as low bone density and increased risk of fracture is prone to occur with the administration of excessive glucocorticoids. Cycloastragenol (CAG) has been verified to be a small molecule that activates telomerase. Studied showed that up-regulated telomerase was associated with promoting osteogeneic differentiation, so we explored whether CAG could promote osteogenic differentiation to protect against GIOP and telomerase would be the target that CAG exerted its function. Our results demonstrated that CAG prominently increased the ALP activity, mineralization, mRNA of runt-related transcription factor 2, osteocalcin, osteopontin, collagen type I in both MC3T3-E1 cells and dexamethasone (DEX)-treated MC3T3-E1 cells. CAG up-regulated telomerase reverse transcriptase and the protective effect of CAG was blocked by telomerase inhibitor TMPyP4. Moreover, CAG improved bone mineralization in DEX-induced bone damage in a zebrafish larvea model. Therefore, the study showed that CAG could alleviate the osteogenic differentiation inhibition induced by DEX in vitro and in vivo, and CAG might be considered as a candidate drug for the treatment of GIOP.

Nitidine chloride (NC) has significant anti-tumor properties; however, the precise mechanism related to NC still needs further investigation. This study intends to investigate the anti-tumor functions and the feasible molecular basis of NC in NSCLC cells. Therefore, we determined the mechanism of NC-mediated anti-tumor function through various methods. Cell proliferation ability and migration and invasion were detected by CCK-8, colony formation assay and Transwell assay, respectively. Furthermore, flow cytometry was used to detect apoptosis, cell cycle and ROS. Moreover, protein expression level was measured by western blot. Our results showed that NC can inhibit the growth, motility of NSCLC cells, induce apoptosis and arrest cell cycle. Meanwhile, NC increased the level of ROS in NSCLC cells. Moreover, western blot data showed that NC suppressed the expression of Lats1, Mob1, and YAP, and enhanced the expression of p-Lats1, p-Mob1, p-YAP1 (ser127). Overall, our research reveals that NC exerts anticancer activity by activating and modulating the Hippo signaling pathway.

Breast cancer has surpassed lung cancer to become the most commonly diagnosed cancer in women worldwide. Sigma-2 (σ

Promising applications of lithium-sulfur batteries with high theoretical capacity are still severely limited due to the poor conductivity of sulfur, the polysulfide shuttle effect and volume expansion. Herein, low-cost and carbon/nitrogen-rich waste honeycombs are used to prepare

Qingfei Paidu decoction (QFPDD) has been clinically proven to be effective in the treatment of coronavirus disease 2019 (COVID-19). However, the bioactive components and therapeutic mechanisms remain unclear. This study aimed to explore the effective components and underlying mechanisms of QFPDD in the treatment of COVID-19 by targeting the virus-host interactome and verifying the antiviral activities of its active components in vitro. Key active components and targets were identified by analysing the topological features of a compound-target-pathway-disease regulatory network of QFPDD for the treatment of COVID-19. The antiviral activity of the active components was determined by a live virus infection assay, and possible mechanisms were analysed by pseudotyped virus infection and molecular docking assays. The inhibitory effects of the components tested on the virus-induced release of IL-6, IL-1β and CXCL-10 were detected by ELISA. Three components of QFPDD, oroxylin A, hesperetin and scutellarin, exhibited potent antiviral activities against live SARS-CoV-2 virus and HCoV-OC43 virus with IC

Colorectal cancer (CRC) is a highly malignant tumor associated with poor prognosis, yet the molecular mechanisms are not fully understood. In this study, we showed that LYAR, a nucleolar protein, is expressed at a higher level in CRC tissue than in adjacent normal tissue and that LYAR expression is closely associated with distant CRC metastasis. LYAR not only significantly promotes the migration and invasion of CRC cells in vitro, but knockdown (KD) of LYAR in CRC cells also inhibits xenograft tumor metastasis in vivo. Microarray analysis of LYAR KD cells combined with a chromatin immunoprecipitation (ChIP) assay, gene reporter assay, and rescue experiment indicated that FSCN1 (encoding fascin actin-bundling protein 1 (Fascin-1)) serves as a novel key regulator of LYAR-promoted migration and invasion of CRC cells. Knockdown of FSCN1 significantly inhibits subcutaneous tumorigenesis of CRC cells and leads to the downregulation of FASN and SCD, genes encoding key enzymes in fatty acid synthesis. In summary, this study reveals a novel mechanism by which LYAR promotes tumor cell migration and invasion by upregulating FSCN1 expression and affecting fatty acid metabolism in CRC.

Nitidine chloride (NC) has been demonstrated to exert a tumor-suppressive function in various types of human cancers. However, the detailed mechanism of NC-mediated anti-tumor effects remains elusive. It has been reported that SIN1, a component of mTORC2 (mammalian target of rapamycin complex C2), plays an oncogenic role in a variety of human cancers. Therefore, the inhibition of SIN1 could be useful for the treatment of human cancers. In this study, we explored whether NC triggered an anti-cancer function via the inhibition of SIN1 in osteosarcoma (OS) cells. An MTT assay was performed to measure the effect of NC on the cell growth of osteosarcoma cells, and flow cytometry was used to detect the apoptotic rate of the cells after NC treatment. The expression of SIN1 was detected by western blotting. Wound-healing assay and Transwell chamber invasion assay were conducted to analyze the motility of osteosarcoma cells following NC exposure. We found that exposure to NC led to the inhibition of cell growth, migration, and invasion and the induction of apoptosis. Mechanistically, we found that NC inhibited the expression of SIN1 in osteosarcoma cells. Overexpression of SIN1 abrogated the inhibition of cell growth and motility induced by NC in osteosarcoma cells. Our results indicate that NC exhibits its tumor-suppressive activity via the inhibition of SIN1 in osteosarcoma cells, suggesting that NC could be a potential inhibitor of SIN1 in osteosarcoma. Keywords: osteosarcoma, nitidine chloride, SIN1, growth, apoptosis, invasion

PDS5B (precocious dissociation of sisters 5B) plays a pivotal role in carcinogenesis and progression. However, the biological functions of PDS5B in lung cancer and its underlying mechanisms are not fully elucidated. In the present study, we used MTT assays, wound-healing assays, and transwell migration and invasion approach to examine the cell viability, migration, and invasion of non-small cell lung cancer (NSCLC) cells after PDS5B modulation. Moreover, we investigated the function of PDS5B overexpression in vivo. Furthermore, we detected the expression of PDS5B in tissue samples of lung cancer patients by immunohistochemical study. We found that upregulation of PDS5B repressed cell viability, migration, and invasion in NSCLC cells, whereas downregulation of PDS5B had the opposite effects. We also observed that PDS5B overexpression retarded tumor growth in nude mice. Notably, PDS5B positively regulated LATS1 expression in NSCLC cells. Strikingly, low expression of PDS5B was associated with lymph node metastasis in lung cancer patients. Our findings suggest that PDS5B might be a therapeutic target for lung cancer.

Alzheimer’s disease (AD) is a chronic progressive degenerative disease of the nervous system. Its pathogenesis is complex and is related to the abnormal expression of the amyloid β (Aβ), APP, and Tau proteins. Evidence has demonstrated that bone morphogenetic protein 4 (BMP4) is highly expressed in transgenic mouse models of AD and that endogenous levels of BMP4 mainly affect hippocampal function. To determine whether BMP4 participates in AD development, transgenic mice were constructed that overexpress BMP4 under the control of the neuron-specific enolase (NSE) promoter. We also performed MTT, FACS, transfection, TUNEL, and Western blotting assays to define the role of BMP4 in cells. We found that middle-aged BMP4 transgenic mice exhibited impaired memory via the Morris water maze experiment. Moreover, their hippocampal tissues exhibited high expression levels of AD-related proteins, including APP, Aβ, PSEN-1, Tau, P-Tau (Thr181), and P-Tau (Thr231). Furthermore, in multiple cell lines, the overexpression of BMP4 increased the expression of AD-related proteins, whereas the downregulation of BMP4 demonstrated opposing effects. Consistent with these results, BMP4 modulation affected cell apoptosis via the regulation of BAX and Bcl-2 expression in cells. Our findings indicate that BMP4 overexpression might be a potential factor to induce AD.

Background: Alzheimer's disease (AD) is a chronic progressive degenerative disease of the nervous system. Its pathogenesis is complex, which is related to abnormal expression of the amyloid b-protein (Ab), APP, and TAU protein. Evidence has demonstrated that bone morphogenetic protein 4 (BMP4) is highly expressed in transgenic mouse models of AD, and endogenous level of BMP4 mainly affects hippocampal function.Methods: To determine whether BMP4 participates in AD development, transgenic mice were constructed with overexpression of BMP4 under control of the neuron-specific enolase (NSE) promoter. We also performed MTT, FACS, Transfection, TUNEL and Western blotting assay to define the role of BMP4 in cells.Results: We found that middle-aged BMP4 transgenic mice exhibited memory disorder via Morris water maze experiment. Moreover, the hippocampal tissues have high expression of AD related proteins including APP, Ab, PSEN-1, TAU, P-TAU (Thr181), and P-TAU (Thr231) proteins. Furthermore, in multiple cell lines, overexpression of BMP4 increased the expression of AD related proteins, whereas downregulation of BMP4 demonstrated opposed effects. Consistently, BMP4 modulation participated in cell apoptosis via regulation of BAX and Bcl-2 expression in cells. Conclusion: Our findings indicate that BMP4 overexpression might be a potential factor to induce AD.

Background Integration of Chinese medical drugs (CMD) and western medicine (WM) has been widely used in the treatment of Coronavirus Disease 2019 (COVID-19). This systematic review aimed to evaluate the efficacy and safety of CMD for COVID-19. Method A literature search was performed in six databases from injection to June 2020. Both randomized controlled trials (RCTs) and quasi-RCTs were considered as eligible. The quality of included RCTs were assessed by Cochrane Risk of Bias Tool, and Review Manager 5.3 software was used to do meta-analysis. Result Eleven studies with 1259 patients were included in this study. CMD included herbal decoction and Chinese patent medicine. The methodological quality was evaluated as generally unclear. The results of meta-analysis showed that the integration of CMD and WM had better efficacy than WM in number of patients turned to severe and critical type (RR = 0.47, 95% CI=[0.32, 0.69], P

RING-in-between-RING (RBR) E3 ligases are one class of E3 ligases that is characterized by the unique RING-HECT hybrid mechanism to function with E2s to transfer ubiquitin to target proteins for degradation. Emerging evidence has demonstrated that RBR E3 ligases play essential roles in neurodegenerative diseases, infection, inflammation and cancer. Accumulated evidence has revealed that RBR E3 ligases exert their biological functions in various types of cancers by modulating the degradation of tumor promoters or suppressors. Hence, we summarize the differential functions of RBR E3 ligases in a variety of human cancers. In general, ARIH1, RNF14, RNF31, RNF144B, RNF216, and RBCK1 exhibit primarily oncogenic roles, whereas ARIH2, PARC and PARK2 mainly have tumor suppressive functions. Moreover, the underlying mechanisms by which different RBR E3 ligases are involved in tumorigenesis and progression are also described. We discuss the further investigation is required to comprehensively understand the critical role of RBR E3 ligases in carcinogenesis. We hope our review can stimulate the researchers to deeper explore the mechanism of RBR E3 ligases-mediated carcinogenesis and to develop useful inhibitors of these oncogenic E3 ligases for cancer therapy.

Background The occurrence of segmental/lobar pattern pneumonia (S/L-PP) in children has recently increased. The pathogens of the disease may change for the misuse of antibiotics and the application of vaccines. Therefore, pathogens positive in hospitalized children with S/L-PP and their association with clinical characteristics may have changed. The aim of this study was to analyze the pathogens positive in hospitalized children with S/L-PP and their association with clinical characteristics. Method The current study analyzed the epidemiological and clinical characteristics of pathogens positive in children with S/L-PP under 14 years old at a single hospital between 1st Jan 2014 and 31st Dec 2018 retrospectively. The pathogens were detected by microbial cultivation, indirect immunofluorescence of the kit (PNEUMOSLIDE IgM), Elisa, and/or real-time PCR in the samples of the patients. Results A total of 593 children with S/L-PP received treatment at a single hospital during the study period by inclusion criteria. Four hundred fifty-one patients were single positive for one pathogen and 83 patients were positive for at least 2 pathogens. Mycoplasma pneumoniae (M.pneumoniae) (72.34%) was the most commonly detected pathogen, followed by Streptococcus pneumoniae (S.pneumoniae) (8.77%). The prevalence of M.pneumoniae in children with S/L-PP increased with time (p p p Conclusion M.pneumoniae was the most positive pathogen in children with S/L-PP. The positive rate of M.pneumoniae in children with S/L-PP increased with time and the ages of children. M.pneumoniae was associated with extrapulmonary manifestations while S.pneumoniae was associated with abnormal WBCs and CRPs.

Ethnopharmacological relevance Traditional Chinese medicine (TCM) holds a great promise for preventing complex chronic diseases through a holistic way. Certain Chinese medicine formulae from TCM are effective for treating and preventing cancer in clinical practice. Xiaoai Jiedu Recipe (XJR) is a Chinese medicine formula that has been used to treat breast cancer (BC). However, its active ingredients and therapeutic mechanisms on tumor are unclear. Therefore, further investigation is necessary. Aim of the study This study aims to elucidate the active compounds of XJR and its molecular mechanisms for the treatment of BC. Materials and methods A comprehensive approach was used to clarify the pharmacodynamic basis of XJR and its pharmacological mechanism, including the acquisition of differentially expressed genes of BC, screening of active ingredients and their targets, construction of complex internetwork between drugs and diseases, and analysis of the key subnetwork. Finally, these results were validated by in vitro experiments and comparison with literature reviews. Results By using bioinformatics, 5211 differentially expressed genes of BC were identified, more than half of them had been reported in previous studies. By using network analysis, 113 potential bioactive compounds in the ten component herbs of XJR and 157 BC-related targets were identified, which were significantly enriched in 85 pathways and 1321 GO terms. The in vitro studies showed that quercetin and ursolic acid, the active components of XJR, could effectively inhibit the proliferation of breast cancer cells, and the combination of the two components could significantly decrease the mitochondrial membrane potential and suppress the activation of PI3K-Akt signaling pathway, thus inducing apoptosis of cancer cells. Conclusions XJR played an important role in anti-BC through multi-component, multi-target and multi-pathway mechanisms, in which quercetin and ursolic acid may be the key active components. The anticancer effect of multi-component application was better than that of a single component. This study not only deepened our understanding of the role of TCM in the prevention and treatment of diseases, but also provided a reference for the in-depth research, development and application of the ancient medicine.

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Heterotopic ossification (HO), true bone formation in soft tissue, is closely associated with abnormal injury/immune responses. We hypothesized that a key underlying mechanism of HO might be injury-induced dysregulation of immune checkpoint proteins (ICs). We found that the earliest stages of HO are characterized by enhanced infiltration of polarized macrophages into sites of minor injuries in an animal model of HO. The non-specific immune suppressants, Rapamycin and Ebselen, prevented HO providing evidence of the central role of the immune responses. We examined the expression pattern of ICs and found that they are dysregulated in HO lesions. More importantly, loss of function of inhibitory ICs (including PD1, PD-L1, and CD152) markedly inhibited HO, whereas loss of function of stimulatory ICs (including CD40L and OX-40L) facilitated HO. These findings suggest that IC inhibitors may provide a therapeutic approach to prevent or limit the extent of HO.

The LiMn1 − xFexPO4/C cathode materials with different Fe2+ contents (x = 0, 0.2, 0.3 and 0.5) have been successfully synthesised by solid-state reaction method. The crystalline structures and morphologies were characterised through scanning electron microscope and X-ray diffraction (XRD). The electrochemical properties of LiMn1 − xFexPO4/C cathodes were investigated by cyclic voltammetry, galvanostatic charge–discharge and electrochemical impedance tests. The XRD patterns indicate that as-prepared LiMn1 − xFexPO4/C cathodes are solid solution materials between LiMnPO4 and LiFePO4 with well-developed crystallinity. The LiMn0.7Fe0.3PO4/C cathodes deliver the highest capacities of 146.8, 136.6, 127.4 and 117.0 mAh g−1 at 0.05, 0.1, 0.2 and 0.5 C, respectively. Its cyclabilities are excellent under various rates, and a slightly increased capacity of 119.3 mAh g−1 is obtained when cycled at 0.5 C after 50 cycles. In addition, LiMn0.7Fe0.3PO4/C materials own the lowest charge transfer impedance of 348.1 Ω, and...

The majority of premalignant gastric lesions develop in the mucosa that has been modified by chronic inflammation. As components of the gastritis microenvironment, mesenchymal stem cells (MSCs) and macrophages are critically involved in the initiation and development of the chronic gastritis-associated gastric epithelial lesions/malignancy process. However, in this process, the underlying mechanism of macrophages interacting with MSCs, particularly the effect of macrophages on MSCs phenotype and function remains to be elucidated. The present study revealed that human umbilical cord-derived MSCs were induced to differentiate into cancer-associated fibroblasts (CAFs) phenotype by co-culture with macrophages (THP-1 cells) in vitro, and which resulted in gastric epithelial lesions/potential malignancy via epithelial-mesenchymal transition-like changes. The results of the present study indicated that macrophages could induce MSCs to acquire CAF-like features and a pro-inflammatory phenotype to remodel the inflammatory microenvironment, which could potentiate oncogenic transformation of gastric epithelium cells. The present study provides potential targets and options for inflammation-associated gastric cancer prevention and intervention.

Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are intracellular pattern recognition receptors (PRRs) that regulate a variety of inflammatory and host defense responses. Unlike the well-established NLRs, the roles of NLRP2 are controversial and poorly defined. Here, we report that NLRP2 acts as a negative regulator of TANK-binding kinase 1 (TBK1)-mediated type I interferon (IFN) signaling. Mechanistically, NLRP2 interacted directly with TBK1, and this binding disrupted the interaction of TBK1 and interferon regulatory factor 3 (IRF3), which interfered with TBK1-induced IRF3 phosphorylation. IFNs induce a series of proteins that have well-known antiviral or immune-regulatory functions, and tight control of the IFN signaling cascade is critical for limiting tissue damage and preventing autoimmunity. Our studies indicate that the NLRP2-TBK1 axis may serve as an additional signaling cascade to maintain immune homeostasis in response to viral infection.

Based on the energy consumption survey in Wuhan, the paper provides the civil building energy consumption quotas according to the three energy efficiency indicators, which include the limit value, the admission value and the advanced value. The paper also presents the uses of different energy consumption quotas and analyses the difference between them. Adopting a statistical analysis method, the paper analyses the limit values of 39 kinds of building using SPSS software. Adopting a simulation method and a device isolation method, the paper provides 15 kinds of admission values and advanced values using DeST simulation software based on energy efficiency design standards. The paper also analyses that judging and excluding outliers are the basis for accurately formulating energy quotas. According to the building energy efficiency and fair principle, the paper gives unit building area energy consumption indicators for buildings with 39 kinds of different functions, air conditioning and heating energy consump...