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Allogeneic grafts are vulnerable to the attack launched by host alloreactive T cells, which accounts primarily for allograft failure in the clinic. Conventional pharmacological intervention mainly involves broad‐acting, nonspecific immunosuppressants that provide limited protection over the graft and may cause deleterious side effects due to insufficient allospecificity. Here, core–shell structured nanoparticles co‐loaded with allogeneic antigen (Ag) and immunosuppressive agent Tacrolimus (Ag@FK506‐NPs) are constructed. Dendritic cells (DCs) pulsed with Ag@FK506‐NPs present alloantigenic epitopes on the cell surface as a bait to capture specific T cells, especially CD8+ T cells, for intercellular FK506 transfer and alloreactive T‐cell deletion. Meanwhile, DCs are maintained in an immature tolerogenic state that induces the functional inactivation of recruited T cells. Compared with free FK506, the adoptive transfer of low immunosuppressant dose (25 000‐fold lower) of Ag@FK506‐NPs pulsed DCs is enough to yield a superior antirejection effect in a major histocompatibility complex‐mismatched murine skin transplant model. Of note, due to the cell–cell communication conferred selective T‐cell suppression, the recipient mouse is able to respond to the subsequent stimulation of an irrelevant Ag, indicating that off‐target toxicity is bypassed. Overall, this work may address some of the limitations of current allograft therapeutics. [ABSTRACT FROM AUTHOR]

Compared to fixed orthodontic appliances with brackets, thermoplastic invisible orthodontic aligners offer several advantages, such as high aesthetic performance, good comfort, and convenient oral health maintenance, and are widely used in orthodontic fields. However, prolonged use of thermoplastic invisible aligners may lead to demineralization and even caries in most patients' teeth, as they enclose the tooth surface for an extended period. To address this issue, we have created PETG composites that contain piezoelectric barium titanate nanoparticles (BaTiO3NPs) to obtain antibacterial properties. First, we prepared piezoelectric composites by incorporating varying amounts of BaTiO3NPs into PETG matrix material. The composites were then characterized using techniques such as SEM, XRD, and Raman spectroscopy, which confirmed the successful synthesis of the composites. We cultivated biofilms of Streptococcus mutans (S. mutans) on the surface of the nanocomposites under both polarized and unpolarized conditions. We then activated piezoelectric charges by subjecting the nanocomposites to 10 Hz cyclic mechanical vibration. The interactions between the biofilms and materials were evaluated by measuring the biofilm biomass. The addition of piezoelectric nanoparticles had a noticeable antibacterial effect on both the unpolarized and polarized conditions. Under polarized conditions, nanocomposites demonstrated a greater antibacterial effect than under unpolarized conditions. Additionally, as the concentration of BaTiO3NPs increased, the antibacterial rate also increased, with the surface antibacterial rate reaching 67.39% (30 wt% BaTiO3NPs). These findings have the potential for application in wearable, invisible appliances to improve clinical services and reduce the need for cleaning methods. [ABSTRACT FROM AUTHOR]

Anlotinib, as a promising oral small-molecule antitumor drug, its role in glioma has been only reported in a small number of case reports. Therefore, anlotinib has been considered as a promising candidate in glioma. The aim of this study was to investigate the metabolic network of C6 cells after exposure to anlotinib and to identify anti-glioma mechanism from the perspective of metabolic reprogramming. Firstly, CCK8 method was used to evaluate the effects of anlotinib on cell proliferation and apoptosis. Secondly, ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based metabolomic and lipidomic were developed to characterize the metabolite and lipid changes in cell and cell culture medium (CCM) caused by anlotinib in the treatment of glioma. As a result, anlotinib had concentration-dependent inhibitory effect with the concentration range. In total, twenty-four and twenty-three disturbed metabolites in cell and CCM responsible for the intervention effect of anlotinib were screened and annotated using UHPLC-HRMS. Altogether, seventeen differential lipids in cell were identified between anlotinib exposure and untreated groups. Metabolic pathways, including amino acid metabolism, energy metabolism, ceramide metabolism, and glycerophospholipid metabolism, were modulated by anlotinib in glioma cell. Overall, anlotinib has an effective treatment against the development and progression of glioma, and these remarkable pathways can generate the key molecular events in cells treated with anlotinib. Future research into the mechanisms underlying the metabolic changes is expected to provide new strategies for treating glioma. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) is a common infectious disease in children. Enterovirus A71 (EV-A71) is one of the main pathogens, and coxsackievirus A6 (CVA6) has gradually become the dominant pathogen of HFMD in recent years. This study was conducted mainly to assess the serological prevalence of EV-A71 and CVA6 antibodies in people of different ages, sexes, and regions through a systematic review and meta-analysis. A comprehensive study was performed based on the EV-A71 and CVA6 serological literature published before May 2022. Heterogeneity analysis (Cochrane's Q test and the I2 statistic) and random effect models were adopted. Subgroup and meta-regression analyses were used to identify potential sources of heterogeneity in the data, and all analysis was performed using STATA version 16.0. This study included 71 studies involving 55,176 people from 13 countries that met the inclusion criteria. The serological prevalence of EV-A71 antibody in different studies was 4.31-88.8%, and that of CVA6 antibody was 40.8-80.9%. Meta-analysis results showed that the serum positive rate for EV-A71 antibody was 45.9% (95% CI: 37.6-54.1%). The rate in the Chinese population was 47.8% (95% CI: 42.4-53.2%), and in the other countries, it was 38% (95% CI: 23-55%). The serum positive rate for CVA6 antibody was 58.3% (95% CI: 46.5-70.2%). The rate in the Chinese population was 49.1% (95% CI: 38.3-59.9%), and in the other countries, it was 68% (95% CI: 51-83%). Subgroup analysis was also conducted. The seroprevalence of EV-A71 and CVA6 antibodies is related to age rather than gender or region. The rates of EV-A71 and CVA6 seropositivity are considerably lower in children younger than five years of age. However, the rates gradually increase with age. The findings of this study suggest that children under five years of age may be susceptible to EV-A71 and CVA6. Thus, safety education and vaccination should be strengthened accordingly. This study provides a basis for understanding the risk factors for EV-A71 and CVA6 infection in China and for deciding how to formulate standard preventive measures to prevent the spread of the virus. [ABSTRACT FROM AUTHOR]

In recent years, hazardous wastewater treatment has been a complex and global problem. In this work, by considering the antimicrobial activity of Ag nanoparticles (AgNPs) and reduced graphene oxide (rGO), we constructed an antibacterial device (G-AgNP) with AgNPs conformably deposited onto a 3D scaffold of reduced graphene oxide in situ. The major limitation, which is difficult to recycle, of two-dimensional graphene-silver composite materials in previous studies is improved. Characterization techniques, SEM, TEM, XRD, and XPS, confirmed the synthesis of nanocomposites. Attributed to its larger specific area, more active sites, and synergistic enhancement, the G-AgNP device demonstrated the best bacterial removal capacity, with an antibacterial rate for both E. coli and S. aureus as high as 100% at quite low AgNP contents. The reported G-AgNP has potential application as a wearable sewage treatment device and for the protection of wearable sensors as a promising sterilizing candidate based on its high and stable antibacterial efficiency. [ABSTRACT FROM AUTHOR]

Cracking of Akebia trifoliata fruit at maturity is problematic for the cultivation of the horticultural crop, shortening shelf-life quality and compromising commercial value. However, the molecular mechanisms underlying this feature of A. trifoliata are not known. Genes involved in cell wall metabolism were identified by genome and transcriptome sequencing, which may play important roles in fruit cracking. One of the galactose metabolism related genes, β-galactosidase (AtrBGAL2), was identified in A. trifoliata , and overexpression (OE) of AtrBGAL2 resulted in early fruit cracking, higher water-soluble pectin contents, and lower acid-soluble pectin, cellulose, and hemicellulose content compared to the wild type. Whereas silencing of AtrBGAL2 in trifoliata by virus induced gene silencing showed opposite trends. The levels of AtrBGAL2 transcripts were 24.6 and 66.0-fold higher in OE A. trifoliata and tomato fruits, respectively, and the cell wall-related genes were also gradually greater than in control plants during fruit ripening. Whereas the expression levels of AtrBGAL2 was significantly down-regulated by 54.1 % and 73.7 % in gene silenced A. trifoliata and CRISPR/Cas9 tomato mutant plants, respectively, and cell wall-related genes were also significantly reduced. These results demonstrate that AtrBGAL2 plays important roles in regulating fruit cracking during fruit ripening. [ABSTRACT FROM AUTHOR]

Hydrothermal method is widely used in the synthesis of perovskite-type oxides, whereas few studies are reported for the nucleation mechanism, so that the relationship between the crystal structures and reactive activities of reactants and products is still unknown. Herein, the reaction processes are analyzed on the basis of XRD, SEM and Raman characterizations, and the nucleation mechanism is investigated for the hydrothermal synthesis of MZrO 3 (M = Ba, Sr, Ca). We propose that the negative charged cyclic tetramer complexes [Zr 4 (OH) 8 (OH) 16 ]8- form in the hydrothermal reaction, which play major roles in the nucleation process. The tetramer complexes continually dehydrate and condensate to form substructural units composed of alkali-earth ions and 6-fold Zr tetramers; substructural units further dehydrate and distort to form perovskite structures. The reactive activation energy increases with the decreasing of M2+ (M = Ba, Sr, Ca) ionic radius because the incorporation of smaller A site ions in the perovskite structure is accompanied by greater rotation and distortion of the ZrO 6 octahedra, leading to the decrease of reactive activity accordingly. In a word, the proposed nucleation mechanism in this paper is of great significance for the study of perovskite. [ABSTRACT FROM AUTHOR]

The growing complexity of real-world systems entails using policy portfolios rather than a single policy instrument to achieve multiple policy goals regarding sustainability. Crucial difficulties include identifying and evaluating policies and their applicable scenarios given numerous combinations. To address these issues, this research develops scenario-based policy representative exploration (SPRE), a systematic approach to exploring policy portfolios, discovering scenarios, and evaluating scenario-specific policy effectiveness in achieving multiple policy goals. SPRE is applied to a low-carbon energy diffusion model. Six policy goals are considered, including low-carbon diffusion rate, cumulative carbon taxes, subsidies, penalties, net interventions, and low-carbon profit. The resultant 232 Pareto-optimal policy portfolios are clustered into five categories and evaluated through representative policy analysis. The findings indicate the basic production profit of unit product and technology-push effect are significant scenario components influencing policy success; the initial proportion of low-carbon adopters or relative carbon reduction ratio do not contribute prominently to policy efficacy. The efficacies of policies are also distinguished in the discovered scenarios: subsidies are effective for the low-carbon transition when the marginal profit of un-low-carbon enterprises is low; carbon taxes and penalties are partially interchangeable; punitive policies are a double-edged sword that can harm potential low-carbon adopters with low profit. • Developing the SPRE framework for policy exploration. • Unit production profit and technology-push effect are crucial to policy success. • Initial low-carbon adoption proportion or relative carbon reduction ratio is not pivotal. • Subsidies are effective when profits for un-low-carbon enterprises are low. • Punitive measures are effective but should avoid harming potential low-carbon adopters. [ABSTRACT FROM AUTHOR]

Brown rot caused by Monilinia fructicola is one major disease in harvested peach fruit. Natural volatile compounds (VOCs) produced by antagonistic microorganisms have good biocontrol effects on postharvest fungal diseases. The present study showed the VOCs of Bacillus cereus N4 isolated from the orchard soil could significantly inhibit the sporulation and mycelial growth of M. fructicola. The expression levels of MfRGS2 , MfRGS3 and MfLTF2α , which are unfavorable to the sporulation of M. fructicola were significantly induced by the VOCs of B. cereus N4. Moreover, the expression levels of MfRGS1 , MfRGS4 , MfREG1 , MfPPOA and MfOPT1 , which are beneficial to the sporulation of M. fructicola were markedly repressed. After fumigated with the VOCs of B. cereus N4 then inoculated with M. fructicola , peach fruit exhibited markedly lower disease incidence and lesion diameter than the control. Moreover, the activity of CHI and the expression level of PpCHI and PpPR1 of the fruit were significantly improved. 3-methyl-1-butanol, s-methyl butanethioate and 2-methyl-2-(methylthio)propane were the main antifungal substances in the VOCs of B. cereus N4 identified by gas chromatograph-mass spectrometer (GC-MS). Overall, the study provides natural candidates antibacterial agent from a biocontrol agent B. cereus N4 to restrain brown rot of peach fruit caused by M. fructicola. • Growth of M. fructicola was repressed by volatile compounds (VOCs) of B. cereus N4. • Brown rot of peach fruit was inhibited by VOCs of B. cereus N4. • The expression of spore germination genes was modulated by VOCs of B. cereus N4. • The major functional component of VOCs was s-methyl butanethioate. [ABSTRACT FROM AUTHOR]

Objective. Oral leukoplakia (OLK) is the most common precancerous lesion in the oral cavity. This study aimed to explore key biomarkers for monitoring OLK for early diagnosis of oral squamous cell carcinoma (OSCC) and screen small-molecule drugs for the prevention of OSCC. Method. The Gene Expression Omnibus (GEO) database was explored to extract two microarray datasets, namely, GSE85195 and GSE25099. The data of the normal group, OLK group, and OSCC group were analyzed by weighted gene coexpression network analysis (WGCNA) to identify the most significant gene module and differentially expressed genes (DEGs). The intersection genes were extracted as the key genes of OLK carcinogenesis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed in the module. Connectivity Map and molecular docking were used to screen small-molecule drugs. The diagnostic values of four key genes were identified and verified in the GSE26549 dataset. Results. WGCNA obtained the red module (r = −0.91, p < 0.05) with the strongest correlation with cancerous phenotype. GO enrichment analysis showed 60 pathways, including 28 biological processes, 11 cell components, and 21 molecular functions, and KEGG enrichment analysis showed 4 pathways (p < 0.05). In the differential expression analysis, there was no intersection between the upregulated genes and the red module genes. However, the intersection of the downregulated genes and the red module genes yielded 4 key genes: dopachrome tautomerase (DCT), keratin 3 (KRT3), keratin 76 (KRT76), and FAM3 metabolic regulation signal molecule B (FAM3B). The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913–1.000). The sensitivity was 0.933, and the specificity was 0.923. The diagnostic model was successfully verified in GSE26549 (AUC = 0.745, CI = 0.638–0.851). Compared with the diagnostic models of the previous studies, the diagnostic efficiency of this model was the highest. The small-molecule drugs, selumetinib and benidipine, were selected according to the gene expression profile and showed binding activity when docking with the above molecules. Conclusions. This study provides new targets and drugs for OLK. These targets could be used as the key diagnostic molecules for long-term follow-up of OLK. The small-molecule drugs selumetinib and benidipine could be used for the prevention and treatment of OSCC. [ABSTRACT FROM AUTHOR]

As a research hotspot, immune checkpoint inhibitors (ICIs) is often combined with other therapeutics in order to exert better clinical efficacy. To date, extensive laboratory and clinical investigations into the combination of ICIs and chemotherapy have been carried out, demonstrating augmented effectiveness and broad application prospects in anti-tumor therapy. However, the administration of these two treatment modalities is usually randomized or fixed to a given chronological order. Nevertheless, the pharmacological effect of drug is closely related to its exposure behavior in vivo , which may consequently affect the synergistic outcomes of a combined therapy. In this study, we prepared a lipid nanoparticle encapsulating docetaxel (DTX-VNS), and associated it with the immune checkpoint inhibitor anti-PD-1 antibody (αPD-1) for the treatment of malignant tumors. To identify the optimum timing and sequencing for chemotherapy and immunotherapy, we designed three administration regimes, including the simultaneous delivery of DTX-VNS and αPD-1(DTX-VNS@αPD-1), DTX-VNS delivery before (DTX-VNS plus αPD-1) or post (αPD-1 plus DTX-VNS) PD-1 blockade with an interval of two days. Analysis from mass spectrometry, multi-factor detection and other techniques indicated that DTX-VNS plus αPD-1 initiated a powerful anti-tumor response in multiple tumor models, contributing to a remarkably reshaped tumor microenvironment landscape, which may attribute to the maximum therapeutic additive effects arise from a concomitant exposure of DTX-VNS and αPD-1 at the tumor site. By profiling the exposure kinetics of nanoparticles and αPD-1 in vivo , we defined the administration schedule with utmost therapeutic benefits, which may provide a valuable clinical reference for the rational administration of immunochemotherapy. We here reveal that the sequencing for chemotherapy and immunotherapy is closely related to the synergistic anti-tumor outcomes. Therefore, profiling the exposure kinetics of chemotherapeutic agent and αPD-1 in vivo may guide the identification of optimum administration schedule with utmost therapeutic benefits in clinical practice. [Display omitted] • Rational administration of immunochemotherapy. • Immune checkpoint inhibitors (ICIs). • Mass cytometry. • Antitumor immunity. [ABSTRACT FROM AUTHOR]

The cross presentation of exogenous antigen (Ag) by dendritic cells (DCs) facilitates a diversified mode of T-cell activation, orchestrates specific humoral and cellular immunity, and contributes to an efficient anti-tumor immune response. DCs-mediated cross presentation is subject to both intrinsic and extrinsic factors, including the homing and phenotype of DCs, the spatiotemporal trafficking and degradation kinetics of Ag, and multiple microenvironmental clues, with many details largely unexplored. Here, we systemically review the current mechanistic understanding and regulation strategies of cross presentation by heterogeneous DC populations. We also provide insights into the future exploitation of DCs cross presentation for a better clinical efficacy in anti-tumor therapy. Up-regulating the cross presentation of DCs might be promising in boosting the anti-tumor immunity. The commonly used regulation strategies of DCs-based cross presentation include extending the Ag stability, optimizing the overall immune environment or DCs-stimulating factors, targeting LNs or DCs for Ag delivery, and regulating the timing and phase of immune response. [Display omitted] [ABSTRACT FROM AUTHOR]

Lipopeptides, a class of compounds consisting of a peptide ring and a fatty acid chain, are secondary metabolites produced by Bacillus spp. As their hydrophilic and oleophilic properties, lipopeptides are widely used in food, medicine, environment and other industrial or agricultural fields. Compared with artificial synthetic surfactants, microbial lipopeptides have the advantages of low toxicity, high efficiency and versatility, resulting in urgent market demand and broad development prospect of lipopeptides. However, due to the complex metabolic network and precursor requirements of synthesis, the specific and strict synthesis pathway, and the coexistence of multiple homologous substances, the production of lipopeptides by microorganisms has the problems of high cost and low production efficiency, limiting the mass production of lipopeptides and large-scale application in industry. This review summarizes the types of Bacillus-produced lipopeptides and their biosynthetic pathways, introduces the versatility of lipopeptides, and describes the methods to improve the production of lipopeptides, including genetic engineering and optimization of fermentation conditions. [ABSTRACT FROM AUTHOR]

The kynurenine pathway (KP) is the principal metabolic route for the essential amino acid tryptophan (TRP). Recent advances have highlighted a pivotal role for several KP metabolites in inflammatory diseases, including ulcerative colitis (UC). However, the alterations of KP enzymes and their functional impact in UC remain poorly defined. Here, we focused on kynurenine 3-monooxygenase (KMO) and kynureninase (KYNU), which serve as critical branching enzymes in the KP. We observed that dextran sodium sulfate (DSS)-induced colitis mice exhibited disturbed TRP metabolism along with KMO and KYNU upregulated. In patients with active UC, both the expression of KMO and KYNU were positively correlated with inflammatory factors TNF-α and IL-1β. Pharmacological blockade of KMO or genetic silencing of KYNU suppressed IL-1β-triggered proinflammatory cytokines expression in intestinal epithelial cells. Furthermore, blockage of KMO by selective inhibitor Ro 61-8048 alleviated the symptoms of DSS-induced colitis in mice, accompanied by an expanded NAD+ pool and redox balance restoration. The protective role of Ro 61-8048 may be partly due to its effect on KP regulation, particularly in enhancing kynurenic acid production. In summary, our study provides new evidence for the proinflammatory property of KMO and KYNU in intestinal inflammation, hinting at a promising therapeutic approach in UC through targeting these enzymes. • KMO and KYNU expression is elevated in mice with acute colitis and patients with active UC. • KMO blockade or KYNU knockdown restricts inflammatory responses in intestinal epithelial cells. • KMO blockade ameliorates experimental colitis, with redox balance re-established. • KMO blockade regulates the imbalanced kynurenine pathway and promotes KYNA production. • Manipulating the KP through selective targeting critical enzymes KMO or KYNU may represent a new therapeutic strategy in UC. [ABSTRACT FROM AUTHOR]

Modern drug delivery system (DDS) exerts its unique superiority as to enhancing drug efficacy while reducing their toxicity, which relies heavily on an accurate route of delivery. Based on the fact that most drugs have their own specific target of action, increasing attention is paid to developing strategies for targeting certain tissues, cell lines, and even intracellular structures. Endoplasmic reticulum (ER) is a dynamic and versatile subcellular organelle that participates in multiple physiological and biochemical processes, supporting the survival and homeostasis-maintenance of cells. Genetic or environmental damages may induce ER stress, which is closely coupled to the occurrence and development of many human diseases and even cancers. In this review, recent progress in strategies of direct ER-targeting with specific molecules or carriers are summarized. We also discuss several advances in fields of indirect ER-targeting. This work may provide a deeper understanding over the ER biology and boost the development of precise intracellular regulation, displaying broad prospects of application. [ABSTRACT FROM AUTHOR]

Here we present the implementation of 213-nm ultraviolet photodissociation (UVPD) in a FT-ICR mass spectrometer for chiral differentiation in the gas phase. The l/d amino acid–substituted serine octamer ions were selected as examples of diastereoisomers for chiral analysis. Several kinds of fragment ions were observed in these experiments, including fragment ions that are similar to the ones observed in corresponding collision-activated dissociation (CAD) experiments, fragment ions generated with different protonation sites by only destroying non-covalent bonds, and unique non-covalent cluster radical ions. The latter two kinds of fragment ions are found to be more sensitive to the chirality of the substituted units. Further experiments suggest that the formation of radical ions is mainly affected by chromophores on side chains of the substituted units and micro surroundings of the characterized non-covalent diastereoisomers. A comparing experiment performed by only changing the wavelength of UV laser to 266 nm shows that the 213-nm UV laser has the priority in the diversity of fragmentation pathways and potential of further application in chiral differentiation experiments. [ABSTRACT FROM AUTHOR]

Dendrobium officinale polysaccharides (DOP) has been reported to possess remarkable effects on improving renal function, oxidative stress damage and fibrotic diseases. However, the role and mechanism of DOP in preventing and treating renal fibrosis remain unclear. The purpose of this paper was to explore the therapeutic effects and underlying mechanisms of DOP on renal fibrosis. Firstly, renal fibrosis model was induced by unilateral ureteral obstruction operation (UUO) in male BALB/c mice. Subsequently, the anti-renal fibrosis effect of DOP was evaluated. It turned out that DOP significantly attenuated UUO induced renal fibrosis. The beneficial effects of DOP on renal fibrosis were concretely manifested in the relief of clinical symptoms, improvement of renal function, reduction of extracellular matrix collagen aggregation, attenuation of structural damage and inflammation, and decrement of profibrotic factors secretion. Meanwhile, DOP could also alleviate oxidative stress injury and inhibit the AhR/NOX4 pathway proteins expression. Furthermore, multivariate statistical analysis, AhR interference and overexpression experiments showed that the effect of DOP on alleviating renal fibrosis was closely related to the improvement of oxidative stress injury mediated by the AhR/NOX4 pathway. Overall, the data in the present paper indicated that DOP could alleviate renal fibrosis through improving AhR/NOX4 mediated oxidative stress injury. [Display omitted] • The Dendrobium officinale polysaccharides (DOP) could improve renal fibrosis (RF). • DOP could relieve the state of oxidative stress injury induced by RF. • DOP could regulate AhR/NOX4 pathway abnormal activation induced by RF. • Anti-RF role of DOP was related to AhR/NOX4 pathway mediated oxidative stress injury. [ABSTRACT FROM AUTHOR]

Enterovirus D68 (EV-D68), a member of Enterovirus genus of the Picornaviridae family, mainly causes respiratory system-related diseases as well as neurological complications in some patients. At present, there is no effective vaccine or treatment for the virus. The aim of this research was to systematically analyse the molecular epidemiology, recombination and changes in the epitope of EV-D68 in China from 2008 to 2022. Through phylogenetic analysis based on VP1 sequences, it was found that there was limited information about EV-D68 infection before 2011 and that EV-D68 infection was dominated by the A2 gene subtype from 2011 to 2013 and the B3 genotype from 2014 to 2018, during which A2 and B3 were coprevalent and alternately prevalent. We also constructed a phylogenetic tree using the EV-D68 full-length genome sequences, and the genotype of each sequence was consistent with that of the VP1 sequence evolutionary tree. Recombination analysis showed that MH341715 underwent intertypic recombination with the A2 genotype MH341729 at the 5′ untranslated region (5'UTR) and that P1-P3 underwent recombination with the B3 genotype MH341712. The capsid protein VP1 is one of the most important structural proteins. In VP1, the BC-loop (89–105 amino acids) and DE-loop (140–152 amino acids) are the most variable domains on the surface of the virus and are associated with epitopes. In this study, it was found that the dominant amino acid composition of the BC-loop and DE-loop continued to change with the epidemic of the virus; the amino acid composition also differed in different regions of the same genotypes. The ongoing genomic and molecular epidemiology of EV-D68 remains important for predicting emergence of new viruses and preventing major outbreaks of respiratory diseases. • EV-D68 infection was dominated by the A2 gene subtype from 2011 to 2013 and the B3 genotype from 2014 to 2018. • The full-length sequence phylogenetic tree genotype was consistent with the VP1 phylogenetic tree. • MH341715 was produced by recombination of MH341712 with MH341729. • The dominant amino acid composition of the BC-loop and DE-loop continued to change with the epidemic of the virus. [ABSTRACT FROM AUTHOR]

The household sector of China is responsible for 11.7% of national energy consumption and 12.6% of carbon dioxide (CO 2) emissions in 2015. Thus, revealing the determinants of household CO 2 emissions (HCE) is extremely important for national efforts towards emissions mitigation. In this context, this paper investigates the driving forces behind national and regional HCE changes employing a temporal Logarithmic Mean Divisia Index (LMDI) model. It also analyses interregional discrepancies in HCE using a spatial LMDI model. This study decomposes the changes or discrepancies of national and regional HCE from 2000 to 2015 into seven key factors. The temporal analysis indicates that household income is the predominant determinant explaining the increase of HCE, whereas energy intensity is the crucial determinant contributing to the mitigation of HCE. The spatial analysis reveals that the number of households and energy intensity are primary driving forces accountable for growing discrepancies in HCE, followed by household income, energy structure and carbon emission coefficient. The analysis also suggests that resourceful and economically developed regions generally have larger potential for mitigation of HCE. The study concludes with some policy recommendations based on the results. [ABSTRACT FROM AUTHOR]

The aim of the current study was to investigate the expression and role of microRNA-486-5p (miR-486-5p) in hypertrophic scar (HS) formation, and to examine the associated mechanisms. First, miR-486-5p expression was detected in HS tissues and human hypertrophic scar fibroblasts (hHSFs) by reverse transcription-quantitative polymerase chain reaction. Target genes of miR-486-5p were predicted using TargetScan and verified by dual-luciferase reporter assays. To investigate the role of miR-486-5p in HS formation, miR-486-5p was overexpressed in hHSFs through transfection with miR-486-5p mimics. MTT, cell apoptosis and cell cycle assays were preformed to investigate the proliferation, cell apoptosis and cell cycle distribution of hHSFs, respectively. Additionally, protein expression was measured by western blot analysis. The results demonstrated that miR-486-5p expression was significantly decreased in HS tissues and cells. Mothers against decapentaplegic homolog (Smad)2 was a target gene of miR-486-5p, and it was negatively regulated by miR-486-5p. It was also found that Smad2 expression was significantly increased in HS tissues and cells. Further analysis indicated that miR-486-5p mimic transfection inhibited the proliferation, induced cell apoptosis and increased G1/S phase arrest in hHSFs. Furthermore, the expression of cyclin-dependent kinase (CDK)2, CDK4 and apoptosis regulator Bcl-2 was repressed, while apoptosis regulator BAX expression was enhanced by miR-486-5p mimic transfection. Notably, the effects of miR-486-5p mimic on hHSFs were significantly eliminated by Smad2 plasmid transfection. Taken together, these results demonstrated that miR-486-5p inhibited the proliferation, induced apoptosis and increased G1/S phase arrest of hHSFs by targeting Smad2. miR-486-5p may be a promising therapeutic target for HS management. [ABSTRACT FROM AUTHOR]

Highlights • Competition between metallization and protonation/reduction exists in MALDI. • The winner of competition might be changed during the whole process. • Covariance mapping shows metalized and protonated species are negatively correlated. Abstract In order to better understand effects of metal cationization on protonation and reduction in MALDI process, mass spectra of riboflavin complexes with different alkali metal ions generated by a series of laser shots at a fixed target spot were consecutively recorded with the matrix of 2,5-dihydroxybenzoic acid (DHB). Progressive changes in the spectra, including the decrease of reduction extent for the metalized molecule ions and the increase of relative intensities of metalized species compared to protonated species, were observed with the increase of laser shots. Covariance mapping analysis was also performed for the data. Results show that different metalized ions are positively correlated each other; while metalized ions and protonated species are negatively correlated. These results not only reflect competition between metalization and protonation/reduction in laser plume, but also show that the winner of it might be changed during the process of sample consumption by laser irradiation. [ABSTRACT FROM AUTHOR]

The Belt and Road initiative has been gaining attention internationally since its proposal. This study applies complex network theory to the Belt and Road countries’ exchange rate markets by constructing a correlation network for these markets using the detrended cross-correlation coefficient (DCCA cross-correlation coefficient). Results show that the Belt and Road countries’ exchange rate network (BREN) 1 1 Hereinafter referred to as BREN. exhibits a small-world effect and robustness. The network is divided into three clusters by factional analysis. The three clusters correspond to three regions: West Asia, Central Asia and Europe, and Southeast Asia. The cohesion subgroup density between Central Asia and Europe and West Asia is high, and the inter-correlation of the Central Asia and Europe is strong. Moreover, the CNY’s position in the BREN has been significantly improved since the policy was proposed. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM), a complex metabolism disease, which was characterized by metabolic disorders including hyperglycemia, has become a major health problem due to the increasing prevalence worldwide. γ-glutamylcysteine (γ-GC) as an immediate precursor of glutathione (GSH) was originally used for the treatment of sepsis, inflammation bowel disease, and senescence. Here, we evaluated the capacity of γ-GC on diabetes-related metabolic parameters in db/db mice and insulin resistance (IR) amelioration in cells induced by palmitic acid (PA). Our data suggested that γ-GC treatment decreased body weight, reduced adipose tissue size, ameliorated ectopic fat deposition in liver, increased the GSH content in liver, improved glucose control and other diabetes-related metabolic parameters in vivo. Moreover, in vitro experiments showed that γ-GC could maintain the balance of free fatty acids (FFAs) and glucose uptake through regulating the translocation of CD36 and GLUT4 from cytoplasm to plasma membrane. Furthermore, our finding also provided evidence that γ-GC could activate Akt not only via adenylate cyclase (AC)/cAMP/PI3K signaling pathway, but also via IGF-1R/IRS1/PI3K signaling pathway to improve IR and hepatic steatosis. Blocking either of two signaling pathways could not activate Akt activation induced by γ-GC. This unique characteristic ensures the important role of γ-GC in glucose metabolism. Collectively, these results suggested that γ-GC could serve as a candidate dipeptide for the treatment of T2DM and related chronic diabetic complications via activating AC and IGF-1R/IRS1/PI3K/Akt signaling pathways to regulate CD36 and GLUT4 trafficking. [ABSTRACT FROM AUTHOR]

Abstract: Objects: This study aimed to report a novel point mutation associated with juvenile amyotrophic lateral sclerosis (JALS) in a Chinese Han family. Methods: Detailed clinical assessment was applied to two patients, including proband (II‐2) and his mother (I‐2). Next‐generation sequencing (NGS), also known as high‐throughput sequencing in whole exon sequence, was performed in the proband to reach the target region. Sanger sequencing was also used to detect DNA sequence variants of the proband and other three members of his family. Results: The proband (II‐2) and his mother (I‐2) were successfully diagnosed according to the clinical manifestations and physical examination. A novel point mutation c.1157T > C in the exon 10 of the SETX gene was identified in II‐2 and I‐2, resulting in a substitution of methionine (ATG) to threonine (ACG). However, we ultimately did not find the same variant in the other two normal members of his family in addition to 100 unrelated normal subjects. Conclusion: We presented a novel probably pathogenic missense mutation in exon 10 of SETX gene in a Chinese Han family with JALS. [ABSTRACT FROM AUTHOR]

The porous platelet-shaped α-BiO photocatalyst was successfully synthesized by a novel hydrothermal-calcination method assisted with ethylenediamine and polyvinylpyrrolidone. The physical and chemical properties of α-BiO photocatalyst were characterized based on XRD, XPS, SEM, TEM, EDS, UV-Vis DRS, and PL techniques. The influence of preparation conditions on the formation of α-BiO photocatalyst was investigated, and the effect of catalyst dosage and pH value on the EE2 removal rate was also investigated. The synthesized porous platelet-shaped α-BiO photocatalyst exhibited excellent photocatalytic activity for 17α-ethynylestradiol (EE2), and 97.8% of EE2 was removed after 75 min of visible light irradiation using α-BiO as photocatalyst. The reaction rate constant over the porous platelet-shaped α-BiO photocatalyst was 11.6 and 11.4 times of that of traditional α-BiO and N-TiO, respectively. The possible photocatalytic mechanism has been discussed on the basis of the theoretical calculation and the experimental results. The porous platelet-shaped α-BiO was a stable and efficient photocatalyst, proving that it is a promising photocatalyst. [ABSTRACT FROM AUTHOR]

Abstract: Objects: To capture point mutations and short insertions/deletions in 49 previously reported genes associated with Parkinson's disease (PD) in a Chinese pedigree with early‐onset Parkinson's disease (EOPD)‐affected individuals. Methods: Clinical examinations and genomic analysis were performed on 21 subjects belonging to three generations of a Chinese family. Target region capture and high‐throughput sequencing were used for screening 49 genes, which were previously reported to be associated with PD. The direct Sanger sequencing method in all subjects further verified the abnormal DNA fragments in the PARK2 gene. Results: Four family members, including a mother (I‐1) and her three children (II‐2, II‐3, and II‐7), were diagnosed with PD by clinical manifestations and/or PET/CT imaging analyses. Novel compound heterozygous mutations, consisting of a fragment deletion in exon 1 to 2 (EX 1‐2 del) and a splicing point mutation c.619‐1 (G > C) in the 6th intron of the PARK2 gene, were identified in II‐2, II‐3, and II‐7. Individual EX 1‐2 del or c.619‐1 (G > C) mutations were detected in I‐1 and the third generation (III‐2, 3, 5, 10, and 11).Other mutations were not detected in the 49 known PD‐associated genes. Conclusion: Novel compound heterozygous mutations were identified in a Chinese pedigree and might represent a cause of familial EOPD with autosomal dominant inheritance. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) can induce plant disease resistance through signal transduction. The gamma-aminobutyric acid (GABA) shunt possesses different response modes for resisting different pathogens. However, the effect of the GABA shunt in NO-induced plant disease resistance is not clear. Herein, the role of the GABA shunt in the resistance of peach fruit induced by NO against Monilinia fructicola infection was investigated together with possible interaction pathways. NO treatment repressed the disease of peach fruit, increased the endogenous NO content, and enhanced the activities and gene expression of GABA shunt enzymes within 48 h, including glutamate decarboxylase (GAD), GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). However, the NO scavenger 2-(4-carboxyphenyl)− 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) aggravated the disease of peach fruit, and inhibited the activities and gene expression of GABA shunt enzymes. The above results highlighted the importance of the GABA shunt in NO-induced disease resistance of peach fruit. It was noteworthy that the nitrosylated level of GAD4, GABA-T3 and SSADH was up-regulated at 6 and 12 h in NO-treated fruit compared with the control, which might be related to the enhanced GABA shunt activity. Additionally, NO treatment up-regulated the expression of glutamate receptor (PpGLR) and glutamate dehydrogenase (PpGDH), promoted Ca2+ influx, strengthened the activity of the tricarboxylic acid cycle (TCAC), and raised the ATP content and energy charge. Overall, the data indicated that NO treatment induced peach fruit disease resistance by activating the GABA shunt. • NO treatment repressed the brown rot of peach fruit. • Activities and gene expression of GABA shunt enzymes were induced by NO treatment. • Nitrosylated level of GABA shunt enzymes was up-regulated by NO treatment. • NO treatment promoted the expression of PpGLRs and PpGDH , and Ca2+ influx. • NO treatment enhanced TCAC activity and increased ATP content and energy charge. [ABSTRACT FROM AUTHOR]

Background: To explore the role of anti-Mullerian hormone (AMH) in predicting the need to step up recombinant FSH (rFSH) dose following long GnRH agonist protocol in IVF/ICSI cycles of polycystic ovarian syndrome (PCOS) women. Methods: This is a retrospective cohort study of 825 PCOS women undergoing long GnRH agonist protocol enrolled from Jan 2019 to Dec 2021. The daily rFSH dose at which the first response to rFSH were recorded. The dose at which the first response to rFSH was based on folliculometry during follow up in which two or more follicles reached ≥ 11 mm. A receiver operating characteristic (ROC) curve analysis was done to investigate the ability of AMH to predict the need to step up initial rFSH dose. Results: PCOS women who needed to step up initial rFSH dose had a significantly higher AMH compared with those didn't step up initial rFSH dose (11.37 ± 3.25ng/ml vs. 8.69 ± 3.16ng/ml, p < 0.001). In multivariate logistic regression analysis, increased AMH level was an independent factor for the need to step up initial rFSH dose in PCOS patients after adjusted for confounding factors. ROC curve analysis showed AMH could predict the need to step up initial rFSH dose (AUC = 0.738, 95%CI: 0.704–0.773), having 75.4% specificity and 63% sensitivity when the threshold AMH concentration was 9.30ng/ml. 58.8% PCOS women with AMH > 9.30 ng/ml required increased rFSH dose compared to 18.8% of women with AMH ≤ 9.30ng/ml (p < 0.001). Although the clinical pregnancy rate and live birth rate were not significantly different, there was a higher incidence of OHSS among women with AMH > 9.30 ng/ml vs. AMH ≤ 9.30ng/ml (20.8% vs. 15.3%, p = 0.043). Conclusion: PCOS women with AMH > 9.30 ng/ml were resistant to rFSH stimulation and require increased dose for the cycle recruitment of ovarian follicles. [ABSTRACT FROM AUTHOR]

In 5D relativity, the usual 4D cosmological constant is determined by the extra dimension. If the extra dimension is spacelike, one can get a positive cosmological constant Λ and a 4D de Sitter (dS) space. In this paper we present that, if the extra dimension is timelike oppositely, the negative Λ will be emerged and the induced 4D space will be an asymptotic Anti-de Sitter (AdS). Under the minimum assumption, we solve the Kaluza–Klein equation R A B = 0 in a canonical system and obtain the AdS solution in a general case. The result shows that an AdS space is induced naturally from a Kaluza–Klein manifold on a hypersurface (brane). The Lagrangian of test particle indicates the equation of motion can be geodesics if the 4D metric is independent of extra dimension. The causality is well respected because it is appropriately defined by a null higher dimensional interval. In this 5D relativity, the holographic principle can be used safely because the brane is asymptotic Euclidean AdS in the bulk. We also explore some possible holographic duality implications about the field/operator correspondence and the two-points correlation functions. [ABSTRACT FROM AUTHOR]

The α/β-Bi 2 O 3 photocatalyst was successfully synthesized by a novel solvothermal-calcination method. The physical and chemical properties of as-prepared samples were characterized based on XRD, XPS, SEM, TEM, EDS, BET, UV–vis DRS and PL techniques. The synthesized α/β-Bi 2 O 3 photocatalyst exhibited enhanced photocatalytic activity for 17α-ethinylestradiol (EE2), and 96.9% of EE2 was degraded after only 24 min of visible-light irradiation using α/β-Bi 2 O 3 as photocatalyst. The reaction rate constant over α/β-Bi 2 O 3 photocatalyst was 1.42, 2.23, 9.22 and 54.1 times higher than pure β-Bi 2 O 3 , α-Bi 2 O 3 +β-Bi 2 O 3 , α-Bi 2 O 3 and P25 respectively. Effect of catalyst dosage and pH value was investigated. The possible photocatalytic mechanism has been discussed on the basis of the theoretical calculation and the experimental results. α/β-Bi 2 O 3 was a fairly stable and efficient photocatalyst under the studied experimental conditions, proving that the α/β-Bi 2 O 3 photocatalyst was a promising photocatalyst for the practical application. [ABSTRACT FROM AUTHOR]

A novel magnetically separable photocatalyst comprising hollow TiO 2 -SiO 2 -CoFe 2 O 4 (TSC) was prepared. In the TSC photocatalyst, an SiO 2 interlayer between CoFe 2 O 4 core and TiO 2 shell is used to both weaken adverse influence of the magnetic core on photocatalysis and increase the temperature of the transition from anatase to rutile phase TiO 2 , thus increasing the anatase TiO 2 crystallinity. Such an interlayer promotes photocatalytic activity by changing the competition between the injecting process and reacting process of the photogenerated carriers. The photocatalytic activity of TSC was determined for degradation of dye molecules in water under either UV or visible light. The photocatalytic reaction of cationic dyes was governed by OH radicals, while O 2 − was the main active species in the initial photoreaction of anionic dyes. [ABSTRACT FROM AUTHOR]

International stock market forms an abstract complex network through the fluctuation correlation of stock price index. Past studies of complex network almost focus on single country’s stock market. Here we investigate the whole and partial characteristics of international stock market network (ISMN) (hereinafter referred to as ISMN). For the analysis on the whole network, we firstly determine the reasonable threshold as the basic of the following study. Robustness is applied to analyze the stability of the network and the result shows that ISMN has robustness against random attack but intentional attack breaks the connection integrity of ISMN rapidly. In the partial network, the sliding window method is used to analyze the dynamic evolution of the relationship between the Chinese (Shanghai) stock market and the international stock market. The connection between the Chinese stock market and foreign stock markets becomes increasingly closer, and the links between them show a significant enhancement especially after China joined the WTO. In general, we suggest that transnational investors pay more attention to some significant event of the stock market with large degree for better risk-circumvention. [ABSTRACT FROM AUTHOR]

A novel bismuth vanadate-palygorskite (BiVO 4 -Pal) photocatalyst was successfully prepared by a hydrothermal method. The morphology, structure and chemical composition of the composite was characterized. The adsorption capacity and photocatalytic activity under visible light of this composite to tetracycline hydrochloride were also investigated. The results indicated that BiVO 4 was successfully loaded on the Pal. Pal, as a low cost support, improved the adsorption capacity of the photocatalyst, thus increased the contact possibility with the active radicals, hence, the degradation activity of BiVO 4 was improved. The maximum adsorption capacity of BiVO 4 -Pal for tetracycline (TC), calculated by the Langmuir model at 20 °C, was 33.11 mg·g − 1 . The pseudo-first-order degradation rate constant for BiVO 4 -Pal composites was approximately 2.1 times higher than that of pure BiVO 4 , and the photodegradation ratio on the BiVO 4 -Pal composite was 1.4 times greater than that of pure BiVO 4 . In addition, the recovery of the BiVO 4 -Pal composite was carried out after the reaction by calcination at 400 °C for 4 h. The test showed that the prepared BiVO 4 -Pal catalyst was stable during the photodegradation of TC. There was no obvious reduction in the degradation rate of TC over the four successive runs and might be useful for practical applications. [ABSTRACT FROM AUTHOR]

An efficient decoloration method for polysaccharides from the sprouts of Toona sinensis (A. Juss.) Roem (PSTS) by anion exchange macroporous resins (AEMR) was investigated in the present paper. The results suggested that D941 resin offered better decoloration efficiency than other tested resins. Based on single-factor experiments, the optimal decoloration parameters of D941 resin were obtained as follows: temperature of 45 °C, sample initial concentration of 30 mg/ml, pH value of 8.5, static decoloration time of 90 min, dynamic decoloration processing volume of 5.5 BV with the flow rate of 2 BV/h. Decoloration ratio, PSTS recovery ratio and selectivity coefficient were 91.94 ± 1.23%, 90.05 ± 2.35% and 10.92 ± 0.63, respectively. Most of pigment impurities were successfully removed from PSTS solutions after treated by D941 resin, and there was no significant difference in carbohydrate concentration, characteristic groups and molecular weight. Compared with H 2 O 2 oxidation and activated carbon adsorption, this developed method is superior. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to investigate the protective effects of polysaccharides from (PGL) Ganoderma lucidum on bleomycin-induced pulmonary fibrosis in rats. Our study demonstrated that treatment with PGL of 100–300 mg/kg for 28 days led to significant reduction in the pulmonary index, inflammatory cell infiltration and collagen deposition in rats with bleomycin-induced pulmonary fibrosis, which was associated with increased levels of glutathione, glutathione peroxidase, catalase and superoxide dismutase and decreased contents of malondialdehyde and hydroxyproline in the lung. These results indicated that PGL played a positive protective role in the pulmonary fibrosis and its possible mechanism was to improve lung antioxidant ability. [ABSTRACT FROM AUTHOR]

Rejection behavior of five kinds of phthalate acid ester (PAEs) including dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), di-n-octyl phthalate (DnOP) and diethylhexyl phthalate (DEHP) from water sources using lab-fabricated hollow fiber nanofiltration (NF) membranes were investigated. Adsorption kinetic behaviors of PAEs were studied as well as the different operation parameters on the rejection of PAEs. The results showed that the times in which PAEs reach saturation adsorption on membrane surface are different. The equilibrium time increased with the molecular weight of the PAE increase. After the PAE reached adsorption equilibrium, the rejection rates of DMP, DEP, DBP, DnOP and DEHP by NF membranes were 82.3%, 86.7%, 91.5%, 95.1% and 95.4%, respectively. The influence of operation parameters including the operation pressure, pH, ionic strength, and temperature on PAE rejection behaviors were also studied. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to investigate the characterization of a novel polysaccharide from the flesh of Cipangopaludina chinensis , named CCPS n . The results found CCPS n was a white powder, readily soluble in hot water and slightly soluble in water. CCPS n was a homopolysaccharide composed of d -glucose ( d -Glc) with molecular weight of 91.1 kDa. Based on analysis of UV–visible, FT-IR, periodic acid oxidation, Smith degradation, methylation, GM-MS and NMR, the structure of CCPS n was elucidated as follows: the backbone was composed of (1→3) linked α- d -Glc. The branches, consisting of a single (1→3) linked α- d -Glc units and terminal α- d -Glc-4-O-SO 3 − , were attached to the main chain at C-4 positions. The degree of branching was calculated to be about 16.73%. The C-1 of terminal α- d -Glc-4-O-SO 3 − was linked to O-3 of (1→3) linked α- d -Glc in the branches. In addition, the results indicated CCPS n was a sulfated polysaccharide with the sulfate radical content of 9.12%. [ABSTRACT FROM AUTHOR]

A palygorskite (Pal)-supported Cu 2 O–TiO 2 heterojunction composite (Cu 2 O–TiO 2 –Pal) was successfully prepared. The morphology, structure and chemical composition of the composite was characterized, and the adsorption and photocatalytic degradation of tetracycline hydrochloride using this composite was also investigated. The results showed that a layer of TiO 2 − Cu 2 O was successfully loaded on the surface of Pal. The Cu 2 O–TiO 2 –Pal composite had a specific surface area of 93 m 2 ·g − 1 , mesoporous features, and a uniform slit channel. The composite possessed twofold removal ability to TC, including adsorptive capability for the separation and solar-light illuminate photocatalytic in degradation. The maximum adsorption capacity of Cu 2 O–TiO 2 –Pal for TC was 113.6 mg·g − 1 at 20 °C as calculated by the Langmuir model. The pseudo-first-order degradation rate constant of 50 mL of TC with an initial concentration of 30 mg·L − 1 reached 0.0129 min − 1 when the Cu 2 O–TiO 2 –Pal concentration was 1.0 g·L − 1 . The total removal rate of TC reached 88.81% in the presence of Cu 2 O–TiO 2 –Pal. In addition, the composite could be regenerated by calcination at 400 °C and recycled more than three times, which is useful for practical applications. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) is a global healthcare problem and socioeconomic issue that is primarily driven by chronic and/or excessive alcohol consumption. Upon alcohol exposure, parenchymal hepatocytes (HCs) up-regulate endoplasmic reticulum (ER)-localized monooxygenase Cytochrome P450 family 2 subfamily E member 1 (CYP2E1) to accelerate the metabolism of ethanol (EtOH), which concurrently exacerbates the production and accumulation of toxic metabolic intermediates, especially reactive oxygen species (ROS), playing a decisive role in the initiation and perpetuation of alcohol-induced liver injury. ALD patients without timely intervention may develop a spectrum of metabolic and functional disorders in the liver, including hepatic steatosis, hepatitis, fibrosis, and even cirrhosis. However, up to now, there have been no FDA-approved pharmacological or nutritional therapeutics for treating patients with ALD, and an effective amelioration of alcohol-induced hepatotoxicity with satisfactory biosafety is still demanding. In this study, antioxidant Vitamin E-incorporating nanoemulsions modified with ER-targetable small molecule p-dodecylbenzene sulfonamide (p-DBSN) was constructed to load and deliver CYP2E1 inhibitor Clomethiazole (CMZ) to the ER of HCs for site-specific inhibition, which displayed remarkable hepatoprotective effects against chronic alcohol exposure without off-target toxicity, both intravenously injected and orally administrated. Generally, our work may provide a promising nanoplatform for reversing ALD. Here, Vitamin E-incorporating nanoemulsions was constructed to load and deliver Cytochrome P450 family 2 subfamily E member 1 (CYP2E1) inhibitor Clomethiazole (CMZ) to the endoplasmic reticulum (ER) of hepatocytes, which mitigated hepatic oxidative stress upon ethanol exposure, reversing alcoholic liver disease (ALD). [Display omitted] [ABSTRACT FROM AUTHOR]

Autophagy is an important homeostatic process for the degradation of cytosolic proteins and organelles and has been reported to play an important role in cellular responses to pathogens and virus replication. However, the role of autophagy in Coxsackievirus A16 (CA16) infection and pathogenesis remains unknown. Here, we demonstrated that CA16 infection enhanced autophagosome formation, resulting in increased extracellular virus production. Moreover, expression of CA16 nonstructural proteins 2C and 3C was sufficient to trigger autophagosome accumulation by blocking the fusion of autophagosomes with lysosomes. Interestingly, we found that Immunity-related GTPase family M (IRGM) was crucial for the activation of CA16 infection-induced autophagy; in turn, reducing IRGM expression suppressed autophagy. Expression of viral protein 2C enhanced IRGM promoter activation, thereby increasing IRGM expression and inducing autophagy. CA16 infection inhibited Akt/mTOR signaling and activated extracellular signal-regulated kinase (ERK) signaling, both of which are necessary for autophagy induction. In summary, CA16 can use autophagy to enhance its own replication. These results raise the possibility of targeting the autophagic pathway for the treatment of hand, foot, and mouth disease (HFMD). [ABSTRACT FROM AUTHOR]

A novel zwitterionic surfactant N-dodecyl aspartic acid was synthesized with dodecylamine, maleic acid anhydride and sodium hydroxide in ethanol-water as the solvent. The chemical structure of N-dodecyl aspartic acid was characterized by IR, H NMR and MS. The surface properties of the surfactant were studied by measuring the equilibrium surface tensions of the dilute aqueous solutions. The synthesized surfactant can reduce the surface tension of water to 29-32 mN m at temperatures of 298-313 K, the surface activity reaches its highest under mild pH conditions. The water hardness has almost no effect on foam power and foam stability of the surfactant at lower and middle water hardnesses. [ABSTRACT FROM AUTHOR]

• Copolymer and homopolymer of aliphatic polycarbonate diols. • Advantageous performance of the CAPC column over the HAPC and PEG columns. • High-resolution separation of the grob test mixture and alkylbenzene isomers. • High column inertness, repeatability and reproducibility. • Good potential for practical analysis of chemical products and essential oils. This work presents the investigation of two aliphatic polycarbonate diols (CAPC and HAPC) as the stationary phases for capillary gas chromatography (GC). The CAPC and HAPC capillary columns showed moderate polarity and high column efficiency of 3704 – 4545 plates/m measured by n-octanol and naphthalene at 120 °C. It was found that despite their similar chemical compositions, CAPC and HAPC differ largely in their selectivity towards the isomers of alkanes, methylpyridines and xylenes. As demonstrated, the CAPC column exhibits advantageous comprehensive performance over the HAPC column and the commercial PEG column. Particularly, the CAPC column exhibits higher resolving performance towards the isomers indicated above and the Grob mixture than the HAPC column. Also, it shows distinct advantages over the PEG column in separating the Grob mixture, the isomers of diethylbenzenes and cymenes, and practical analysis of chemical products and the essential oil from the leaves of Rhododendron dauricum L. Additionally, the CAPC column has excellent repeatability and reproducibility on analyte retention times with the relative standard deviation (RSD) values in the range of 0.05% – 0.08% for run-to-run, 0.12% – 0.19% for day-to-day and 2.6% – 4.9% for column-to-column, respectively. Its applications to purity test of chemical products and GC–MS analysis of the essential oil demonstrate its promising future for practical GC analyses. [ABSTRACT FROM AUTHOR]

As the central part of cellular immunity, primed CD8+ T cells go through different phases of response including activation, clonal expansion, contraction and steady-state turnover, which is accompanied by a fluctuating level of endoplasmic reticulum stress that leads to the elicitation of unfolded protein response (UPR). In turn, UPR casts profound impacts on the activation-induced biological processes of CD8+ T cells, which may greatly determine the magnitude and quality of T-cell based immunity. However, current understanding of the interconnectivity between UPR and T cell-biology is not comprehensive, with details of manipulation largely unexplored. In this review, the molecular basis of UPR involved in different stages of activated CD8+ T cells and its immunological significance are discussed, with potential strategies of regulation proposed, which may provide instructive guidance for the design and optimization of T cell-based immunotherapy. We here review the molecular basis and immunological significance of unfolded protein response (UPR) involved in different stages of activated CD8+ T cells, and discuss potential regulation strategies of exploiting UPR to boost CD8+ T cell-mediated immune protection, which may provide guidance for the future development of T cell-based immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Transplantation is the most effective, and sometimes the only resort for end-stage organ failure. However, allogeneic graft suffers greatly from lymphocyte-mediated immunorejection, which bears close relationship with a hyperactivation of endoplasmic reticulum (ER) stress response in host lymphocytes, especially in CD8+ T cells (T-8). Therefore, regulating lymphocytic ER unfolded protein response (UPR) might be a potential therapeutic breakthrough in alleviating graft rejection. Here, ER-targetable liposome is prepared via the surface modification of ER-targeting peptide (Pardaxin), which efficiently loads and directly delivers small molecule inhibitor of UPR sensor IRE1α into the ER of lymphocytes, inducing a systemic immunosuppression that facilitates tumorigenesis and metastasis in the tumor inoculation challenge in vivo. And in vitro , a stage-differential dependency of IRE1α in the phase transition of T-8 is identified. Specifically, inhibiting IRE1α at the early responding stages of T-8, especially at the activation phase, results in a shrunk proliferation, impaired effector function, and limited memory commitment, which might contribute centrally to the induced overall immunosuppression. Based on this, a classical acute rejection model, murine full-thickness trunk skin allograft that primary arises from the hyperactivity of T-lymphocyte, is used. Results suggest that lymphocytic IRE1α inactivation attenuates transplant rejection and prolongs graft survival, with a limited effector function and memory commitment of host T-8. Moreover, an even higher immunosuppressive effect is obtained when IRE1α inhibition is used in combination with immunosuppressant tacrolimus (FK506), which might owe to a synergistic regulation of inflammatory transcription factors. These findings provide a deeper insight into the biological polarization and stress response of lymphocytes, which might guide the future development of allogeneic transplantation. We here reveal that endoplasmic reticulum (ER)-targeted abrogation of lymphocytic ER-stress transducer IRE1ɑ induces a systemic immunosuppression to alleviate skin allograft rejection, which displays synergism with immunosuppressant tacrolimus (FK506), probably due to a cooperative regulation over inflammatory transcription factors. Further exploration identified a stage-differential dependency of IRE1ɑ in the phase transition of CD8+ T cells (T-8), which might contribute centrally to the negative immunoregulation of lymphocytic IRE1ɑ inhibition. [Display omitted] [ABSTRACT FROM AUTHOR]

Tetracycline hydrochloride (TC) wastewater has complex components, high concentration of organic matter and certain biological toxicity. Photocatalytic degradation is of great application prospect due to its green, thorough and efficient removal of TC. In this study, heterojunction photocatalyst supported on Palygorskite (Pal) AgBr–TiO 2 -Pal with visible light response was successfully prepared via sol-gel and liquid deposition method successfully. Taking TC as the target pollutant, the photocatalytic performance of AgBr–TiO 2 -Pal photocatalys excited by visible light was studied. The spreading/grafting of AgBr–TiO 2 on the surface of Pal was improved by a series of structural characterization and composition analysis. The results also demonstrated that the specific surface area of AgBr–TiO 2 -Pal was about 48.06 m2⋅g−1 with uniform mesoporous slit. The AgBr–TiO 2 -Pal catalyst was very effective for the degradation of TC, and it still retained its high stability and reusability after five cycles. The results showed that under the best reaction conditions (initial concentration of tetracycline 10 mg⋅L−1, catalyst dosage 0.5 g⋅L−1, pH value 9), with the excitation of visible light, the maximum removal ratio of TC was 90%, and the mineralization ratio was 67%. The removal efficiency and degradation rate of TC by AgBr–TiO 2 -Pal catalyst were 2.17 and 4.75 times as much as those of TiO 2 respectively. The outstanding photocatalytic performance of heterogeneous AgBr–TiO 2 -Pal catalyst was obtained by fully participate in the reaction by photoinduced charge. This study could be expected to be used in photocatalytic degradation of antibiotic pollutants in wastewater treatment. • A novel AgBr–TiO 2 -Pal photocatalyst is prepared for tetracycline degradation. • The catalyst support, Palygorskite, has a porous structure and large surface area. • The AgBr–TiO 2 heterostructure has enhanced visible light photocatalytic activity. • The catalyst can be recycled more than five times by a simply filtered. [ABSTRACT FROM AUTHOR]

In recent years, methods based on photodissociation in the gas phase have become powerful means in the field of chiral analysis. Among them, infrared multiple photon dissociation (IRMPD) spectroscopy is a very attractive one, since it can provide valuable spectral and structural information of chiral complexes in addition to chiral discrimination. Experimentally, the method can be fulfilled by the isolation of target diastereomeric ions in an ion trap followed by the irradiation of a tunable IR laser. Chiral analysis is performed by comparing the difference existing in the spectra of enantiomers. Combined with theoretical calculations, their structures can be further understood on the molecular scale. By now, lots of chiral molecules, including amino acids and peptides, have been studied with the method combined with theoretical calculations. This review summarizes the relative experimental results obtained, and discusses the limitation and prospects of the method. [ABSTRACT FROM AUTHOR]

• The information platform is a double-edged sword for EET diffusion. • Rejecter plateaus may emerge and delay EETs' massive diffusion. • Network densification would promote the diffusion but its effectiveness decays. • High network density and frequent interfirm interactions incur excessive instability. Energy efficiency technologies (EETs) are crucial for saving energy and reducing carbon dioxide emissions. However, the diffusion of EETs in small and medium-sized enterprises is rather slow. Literature shows the interactions between innovation adopters and potential adopters have significant impacts on innovation diffusion. Enterprises lack the motivation to share information, and EETs usually lack observability, which suppress the inter-firm influence. Therefore, an information platform, together with proper policies encouraging or forcing enterprises to disclose EET-related information, should help harness inter-firm influence to accelerate EETs' diffusion. To explore whether and how such an information platform affects EETs' diffusion in small and medium-sized enterprises, this study builds an agent-based model to mimic EET diffusion processes. Based on a series of controlled numerical experiments, some counter-intuitive phenomena are discovered and explained. The results show that the information platform is a double-edged sword that notably accelerates EETs' diffusion by approximately 47% but may also boost negative information to diffuse even faster and delay massive adoption of EETs. Increasing network density and the intensity of inter-firm influence are effective to speed EET diffusion, but their impacts diminish drastically after reaching some critical values (0.05 and 0.15 respectively) and eventually harm the stability of the system. Hence, the findings implicate that EET suppliers should carefully launch their promising but immature products; policies that can reduce the perceived risk by enterprises and the effort to maintain an informative rather than judgmental information platform can prominently mitigate the negative side effects brought by high fluidity of information. [ABSTRACT FROM AUTHOR]

Policy interventions are frequently used by authorities around the world to mitigate carbon emissions. However, economic systems are essentially complex adaptive systems, which often exhibit unexpected responses to exogenous interventions and leave intervenors in a dilemma, even if the interventions are elaborately designed. To explore the behaviors of the diffusion system regarding low-carbon technologies, this study builds an agent-based model (ABM) to simulate enterprises' reactions to multiple policy interventions aimed at spurring low-carbon technology diffusion. The simulated enterprises are in a complex network where they play evolutionary games with their neighbors, which enables the model to possess two critical features of economic systems: adaptiveness and equilibrium. The model reveals a dilemma of policy interventions: intuitively, carbon taxes, asymmetric penalties (only imposed on un-low-carbon enterprises) and subsidies can improve the diffusion, which is consistent with previous research; counter-intuitively, all these policies turn out to be inefficient or even harmful to low-carbon enterprises because of the diffusion system's high adaptiveness. Specifically, when carbon taxes and penalties increase, both the low-carbon and un-low-carbon enterprises end up with the equilibrium of equivalent but lower profits. In contrast, all the enterprises earn equivalent but more profits even though subsidies are only given to the low-carbon enterprises, which implies that the un-low-carbon enterprises (indirectly) grab a portion of the subsidies and accordingly weaken the incentive effect of subsidies. These system behaviors are summarized as "equalizing effect" because the system tends to equalize the impact of both positive and negative interventions among all enterprises even though the policy interventions are asymmetrically imposed on one type of the enterprises. The findings also indicate that policies implemented to enlarge green market sizes can help policymakers bypass the dilemma. [ABSTRACT FROM AUTHOR]