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The application of metal catalysis has gained prominence as a study area in recent years. In this work, we use adsorptive reduction and calcination to create Au–Pd alloy catalysts on COCN-2 with varying metal loadings. The plasma resonance effect of the alloys increases the photoresponse of the catalysts, and the engineering of nitrogen defects strengthens the strong bonds between Au–Pd alloy particles and carbon nitride graphite, optimizing the electronic structure, encouraging electron-directed migration, and increasing the efficiency of the reduction reaction. As a result, the efficiency of hydrogen generation by the Au–Pd 0.6 /COCN-2 catalyst is 5.089 mmol g−1 h−1, which is 2367 times higher than that of the g-C 3 N 4 catalyst. Our findings highlight the crucial part that flaws play in strengthening the strong bonds that exist between the metal and the support, which enhances photocatalytic hydrogen generation. This work offers insightful information about creating effective photocatalysts. • A series of Au–Pd/COCN catalysts were prepared via a facile method. • The performance of Au–Pd 0.6 /COCN-2 reached 5.089 mmol g−1 h−1, which is 2367 times higher than the pristine g-C 3 N 4. • A series of investigations were conducted to reveal the mechanism. [ABSTRACT FROM AUTHOR]

Simple Summary: Understanding the molecular mechanisms involved in feather color formation is important because coloration is one of the most recognizable characteristics in chickens. In this study, after transcrip-tome sequencing of the wing and neck feather follicle tissues of chickens with different plumage colors, we retrieved differentially expressed genes (DEGs) with the same trends in both the wing and neck and then identified DEGs that may be associated with melanin deposition through GO and KEGG annotation and PPI analysis. Finally, we verified that two genes in chicken melanocytes, SLC45A2 and GPNMB, promote melanocyte melanin deposition in chickens. As an essential genetic and economic trait, chicken feather color has long been an important research topic. To further understand the mechanism of melanin deposition associated with coloration in chicken feathers, we selected feather follicle tissues from the neck and wings of chickens with differently colored feathers (yellow, sub-Columbian, and silver) for transcriptome analysis. We focused on genes that were expressed in both the wings and neck and were expressed with the same trends in breeds with two different plumage colors, specifically, SLC45A2, GPNMB, MLPH, TYR, KIT, WNT11, and FZD1. GO and KEGG enrichment analyses showed the DEGs were enriched in melanin-related pathways, such as tyrosine metabolic pathway and melanogenesis, and PPI analysis highlighted the genes SLC45A2 and GPNMB as associated with melanin deposition. Verification experiments in chicken melanocytes demonstrated that these two genes promote melanocyte melanin deposition. These data enrich our knowledge of the mechanisms that regulate chicken feather color. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) progresses rapidly, is difficult to treat, and has a high fatality rate. The excessive inflammatory response is an important pathological mechanism of ALI. NLRC3 (NLR family CARD domain-containing 3), a non-inflammasome member of the NLR family, has been found that it could negatively regulates various biological pathways associated with inflammatory response, such as NF-κB (nuclear factor kappa B), PI3K (Phosphatidylinositol 3′-kinase)-Akt (protein kinase B)-mTOR (mammalian target of the rapamycin), and STING (stimulator of interferon genes) pathways, which are responsible for the progression of pulmonary inflammation and participate in regulating the pathological progression of ALI. However, the effects of NLRC3 in sepsis-induced pathological injury of lung tissue remain unclear. In this study, we aimed to investigate the potential effects of NLRC3 in the sepsis-induced ALI. To investigate whether NLRC3 participates in inhibiting the pulmonary inflammatory response of sepsis-induced ALI. Sepsis-induced ALI mice models were established by intrabronchial injection of lipopolysaccharide (LPS) or cecum ligation and puncture (CLP). The lentivirus with overexpression of NLRC3 (LV-NLRC3) and downregulation of NLRC3 (LV-NLRC3-RNAi) were transfected to LPS-induced ALI mice. The expression of NLRC3 was upregulated or downregulated in the lung tissue of sepsis-induced ALI mice. Transfection with NLRC3-overexpression lentivirus significantly decreased inflammatory response in the lung of LPS-induced ALI mice in contrast to the control group. By transfection with NLRC3-silencing lentivirus, the inflammatory response in LPS-induced ALI mice was aggravated. Our study provides evidence of the protective effect of NLRC3 in sepsis-induced ALI by inhibiting excessive inflammatory response of the lung tissue. AbbreviationsAcute lung injury: ALI; intensive care units: ICU; lipopolysaccharide: LPS; acute respiratory distress syndrome: ARDS; bronchoalveolar lavage fluid: BALF; nucleotide-binding oligomerization domain-like receptors: NLRs; NLR family CARD domain containing 3: NLRC3; nuclear factor kappa B: NF-κB; tumor necrosis factor receptor-associated factor 6: TRAF6; Phosphatidylinositol 3′-kinase: PI3K; protein kinase B: Akt; mammalian target of the rapamycin: mTOR; stimulator of interferon genes: STING; TANK-binding kinase 1: TBK1; type I interferon: IFN-I; toll-like receptors: TLRs; tumor necrosis factor: TNF; interleukin: IL; NOD-like receptor protein 3: NLRP3; enhanced green fluorescent protein: EGFP; lentivirus: LV; phosphate-buffered saline: PBS; intrabronchial: i.t.; cecum ligation and puncture: CLP; wet/dry: W/D; Real time polymerase chain reaction: RT-PCR; enzyme-linked immunosorbent assay: ELISA; hematoxylin and eosin: H&E; radio immunoprecipitation assay: RIPA; sodium dodecyl sulfate polyacrylamide gel electrophoresis: SDS-PAGE; polyvinylidene fluoride: PVDF; glyceraldehyde 3-phosphate dehydrogenase: GAPDH; bovine serum albumin: BSA; Tris buffered saline containing Tween 20: TBST; standard deviation: SD; one-way analysis of variance: ANOVA; janus kinase 2: JAK2; activators of transcription 3: STAT3; pathogen associated molecular patterns: PAMPs; danger associated molecular patterns: DAMPs. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV)-based gene therapy has been shown to be safe and effective in numerous animal models and clinical trials for various ophthalmic diseases. Stargardt disease (STGD1; MIM #248200) is the most common autosomal recessive macular dystrophy disease, and the most common form is caused by mutations in the ABCA4 gene, a gene with 6.8 kb coding sequence. Split intein approaches increase the capacity of dual AAV gene therapy, but at the cost of reduced protein expression, which may be insufficient to achieve a therapeutic effect. In this study, we designed various dual split intein ABCA4 vectors and showed that the efficiency of expression of full-length ABCA4 protein is dependent on combinations of types and split sites of the intein system. The most efficient vectors were identified through in vitro screening, and a novel dual AAV8-ABCA4 vector was constructed and subsequently proven to express full-length ABCA4 protein at a high level, reducing bisretinoid formation and correcting the visual function of ABCA4-knockout mice. Furthermore, we evaluated therapeutic effects of different dosages by subretinal injection in mice model. Both therapeutic effects and safety were guaranteed under the treatment of 1.00 × 109 GC/eye. These results support the optimized dual AAV8-ABCA4 approach in future clinical translation for treatment of Stargardt disease. [ABSTRACT FROM AUTHOR]

The innate immune system is the first line of defense for the host against any microbial attack. It can quickly identify microorganisms and produce an immune response, removing pathogenic microorganisms. However, a strong immune response might lead to excessive inflammation and even autoimmune diseases. NLRC3 is an important regulator of innate immune system homeostasis. It is a member of the anti-inflammatory NLR family and can inhibit excessive immune response in the body. In this review, we primarily focused on the current research progress on NLRC3 and its potential application. It can decrease the production of pro-inflammatory cytokines by inhibiting the NF-κB, MAK-ERK, PI3K-mTOR, IL-6/JAK2/STAT3, and cGAS-STING pathways. It also inhibits inflammatory responses by interfering with the assembly and activity of the NLRP3 inflammasome complexes. Additionally, NLRC3 can also reduce the functions of some antigen-presenting cells and their ability to activate and polarize CD4+ T cells into Th1 and Th17 subsets. NLRC3 is closely related to the development of tumors, infectious diseases, autoimmune diseases, and AD. These diseases might be treated effectively by regulating the expression of NLRC3. • NLRC3 is an important regulator of innate immune system homeostasis. • NLRC3 inhibits Several pro-inflammatory signaling pathways. • NLRC3 interferes with the assembly and activity of the NLRP3 inflammasome complexes. • NLRC3 weakens the function of antigen-presenting cells. • NLRC3 negatively regulates the immune response of CD4+ T cells. [ABSTRACT FROM AUTHOR]

Mutations of the chromosome 9 open reading frame 72 (C9orf72) gene is the most prevalent defect associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The C9orf72 protein interacts with Smith-Magenis syndrome chromosomal region candidate gene 8 (SMCR8) and WDR41 to form a trimeric complex that regulates several cellular pathways including autophagy and membrane trafficking and is strongly linked to familial ALS and FTD. The C9orf72-SMCR8 complex is important for its GTPase activating proteins (GAP) activity and mutations in the dimer interface affects the GAP activity. Mutations at protein-protein interfaces alter the stability and binding affinity of protein-protein complexes and may lead to diseases. In this study, we used computational saturation mutagenesis, including structure-based energy calculations and sequence-based pathogenicity predictions, to quantify the systemic effects of missense mutations of C9orf72 protein stability and binding affinity to Smith-Magenis syndrome chromosomal region candidate gene 8 (SMCR8). A total of 494 interfacial mutations of C9orf72 were analyzed, and we observed that most of these mutations destabilize the protein and decreased the binding to SMCR8. We further analyzed 240 annotated verified C9orf72 missense variations and revealed that most of the mutations affect the stability and the C9orf72-SMCR8 interaction. These findings shed light on the effect of mutations in C9orf72 stability and binding which can successfully predict the functional consequences of mutations on C9orf72 function and may enable researchers to deduce the mechanisms of ALS and FTD. [Display omitted] • C9orf72 (chromosome 9 open reading frame 72) mutations affect protein stability and binding. • Most of the interfacial mutations destabilize the protein and decreased the binding of C9orf72 to SMCR8. • The mutations in α11 residues (392−419) of C9orf72 may significantly change the binding affinity of the C9orf72-SMCR8 complex. • Mutations at residue G403 destabilized C9orf72 and decreased its binding to SMCR8. • Mutations H406Q, H406R, R407I, L410S, and T411R stabilized C9orf72 but at the same time decreased the binding of SMCR8. [ABSTRACT FROM AUTHOR]

Graphitic carbon nitride (g-C 3 N 4) faces limitations in photocatalytic application due to its limited light response and high recombination rate of photo-generated charge carriers. Herein, we synthesized a K, P co-doped g-C 3 N 4 (KPCN) with cyano defects via microwave-assisted heating of the mixture of KH 2 PO 4 and melamine in just 7 min. The KPCN exhibits a reduced bandgap of 2.37 eV and introduces a mid-gap of 1.77 eV, which broadens light absorption to the visible-near-infrared (vis-NIR) spectrum with light absorption to 867 nm. Impressively, the co-doped K and P adjust the interlayer and in-plane electron distribution of g-C 3 N 4 , enhancing charge separation and transfer. The KPCN exhibits a remarkable improvement in H 2 O 2 yield of 7.74 mM g−1 h−1, demonstrating superior catalytic activity compared to microwave pure g-C 3 N 4 (MCN, 5.1 times) and bulk g-C 3 N 4 (BCN, 19.2 times). The results indicate that the K, P co-doped g-C 3 N 4 synthesized rapidly and efficiently by microwave method has relatively stable and considerable photocatalytic activity, which has great potential application in the industrial production of H 2 O 2. • K, P co-doped g-C 3 N 4 (KPCN) was prepared by rapid microwave synthesis in just 7 min. • K, P co-doping optimizes the in-plane electron distribution and interlayer electron migration of g-C 3 N 4. • KPCN exhibits a reduced bandgap from 2.75 eV to 2.37 eV and introduces a mid-gap at 1.77 eV. [ABSTRACT FROM AUTHOR]

The economic losses incurred due to reduced muscle pigmentation highlight the crucial role of melanin-based coloration in the meat of black-bone chickens. Melanogenesis in the breast muscle of black-bone chickens is currently poorly understood in terms of molecular mechanisms. This study employed whole-transcriptome sequencing to analyze black and white breast muscle samples from black-bone chickens, leading to the identification of 367 differentially expressed (DE) mRNAs, 48 DElncRNAs, 104 DEcircRNAs, and 112 DEmiRNAs involved in melanin deposition. Based on these findings, a competitive endogenous RNA (ceRNA) network was developed to better understand the complex mechanisms of melanin deposition. Furthermore, our analysis revealed key DEmRNAs (TYR, DCT, EDNRB, MLPH and OCA2) regulated by DEmiRNAs (g ga-miR-140-5p, gga-miR-1682, gga-miR-3529, gga-miR-499-3p, novel-m0012-3p, gga-miR-200b-5p, gga-miR-203a, gga-miR-6651-5p, gga-miR-7455-3p, gga-miR-31-5p, miR-140-x, miR-455-x, novel-m0065-3p, gga-miR-29b-1-5p, miR-455-y, novel-m0085-3p, and gga-miR-196-1-3p). These DEmiRNAs competitively interacted with DElncRNAs including MSTRG.2609.2, MSTRG.4185.1, LOC112530666, LOC112533366, LOC771030, LOC107054724, LOC121107411, LOC100859072, LOC101750037, LOC121108550, LOC121109224, LOC121110876, and LOC101749016 , as well as DEcircRNAs, such as novel_circ_000158, novel_circ_000623, novel_001518, and novel_circ_003596. The findings from this study provide insight into the mechanisms that regulate lncRNA, circRNA, miRNA, and mRNA expression in chicken melanin deposition. [ABSTRACT FROM AUTHOR]

Background. The cholinergic anti-inflammatory pathway connects the immune response system and the nervous system via the vagus nerve. The key regulatory receptor is the α7-subtype of the nicotinic acetylcholine receptor (α7nAChR). Cholinergic anti-inflammatory pathway has been proved to be effective in suppressing the inflammation responses in acute lung injury (ALI). Dendritic cells (DCs), the important antigen-presenting cells, also express the α7nAChR. Past studies have indicated that reducing the quantity of mature conventional DCs and inhibiting the maturation of pulmonary DCs may prove effective for the treatment of ALI. However, the effects of cholinergic anti-inflammatory pathway on maturation, function, and quantity of DCs and conventional DCs in ALI remain unclear. Objective. It was hypothesized that cholinergic anti-inflammatory pathway may inhibit the inflammatory response of ALI by regulating maturation, phenotype, and quantity of DCs and conventional DCs. Methods. GTS-21 (GTS-21 dihydrochloride), an α7nAchR agonist, was prophylactically administered in sepsis-induced ALI mouse model and LPS-primed bone marrow-derived dendritic cells. The effects of GTS-21 were observed with respect to maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2 (type 2 conventional DCs) and the release of DC-related proinflammatory cytokines in vivo and in vitro. Results. The results of the present study revealed that GTS-21 treatment decreased the maturation of DCs and the production of DC-related proinflammatory cytokines in vitro and in sepsis-induced ALI mouse model; it reduced the quantity of CD11c+MHCII+ conventional DCs and CD11c+CD11b+ conventional DCs2 in vivo experiment. Conclusions. Cholinergic anti-inflammatory pathway contributes to the reduction in the inflammatory response in ALI by regulating maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2. [ABSTRACT FROM AUTHOR]

Background: Nonsuicidal self-injury (NSSI) is related to childhood abuse, family relationships, interpersonal relationships, personality, but the interaction between them is still unclear, and how they interact in major depressive disorder (MDD).Methods: Collected data from 444 undergraduate degree students with MDD participated. Used the Eysenck Personality Questionnaire, Childhood Trauma Questionnaire, Interpersonal Relationship Comprehensive Diagnostic Scale, and Family Assessment Device to assess the patients' psychosocial factors. NSSI behavior was assessed through interviews. Use the Chi-square test, Wilcoxon rank-sum test, Kruskal-Wallis H-test, Distance Correlation, Structural Equation Mode for data analysis.Results: Overall, 34.2% of patients with MDD had a history of NSSI. MDD patients with a history of NSSI had significant differences in psychoticism, neuroticism, emotional abuse, physical abuse, sexual abuse, emotional neglect, troubles in conversation, ability to make friends and family roles. Among these factors, psychoticism was most related to NSSI, and child abuse, interpersonal relationships and family roles played a variety of roles in mediating the relationship with NSSI.Conclusions: Psychosocial factors affect the occurrence of NSSI through chain intermediary effects. [ABSTRACT FROM AUTHOR]

Background: Endothelial progenitor cell (EPC) dysfunction contributes to vascular disease in diabetes mellitus. However, the molecular mechanism underlying EPC dysfunction and its contribution to delayed reendothelialization in diabetes mellitus remain unclear. Our study aimed to illustrate the potential molecular mechanism underlying diabetic EPC dysfunction in vivo and in vitro. Furthermore, we assessed the effect of EPC transplantation on endothelial regeneration in diabetic rats. Methods: Late outgrowth EPCs were isolated from the bone marrow of rats for in vivo and in vitro studies. In vitro functional assays and Western blotting were conducted to reveal the association between C-X-C chemokine receptor type 7 (CXCR7) expression and diabetic EPC dysfunction. To confirm the association between cellular CXCR7 levels and EPC function, CXCR7 expression in EPCs was upregulated and downregulated via lentiviral transduction and RNA interference, respectively. Western blotting was used to reveal the potential molecular mechanism by which the Stromal-Derived Factor-1 (SDF-1)/CXCR7 axis regulates EPC function. To elucidate the role of the SDF-1/CXCR7 axis in EPC-mediated endothelial regeneration, a carotid artery injury model was established in diabetic rats. After the model was established, saline-treated, diabetic, normal, or CXCR7-primed EPCs were injected via the tail vein. Results: Diabetic EPC dysfunction was associated with decreased CXCR7 expression. Furthermore, EPC dysfunction was mimicked by knockdown of CXCR7 in normal EPCs. However, upregulating CXCR7 expression reversed the dysfunction of diabetic EPCs. The SDF-1/CXCR7 axis positively regulated EPC function by activating the AKT-associated Kelch-like ECH-associated protein 1 (keap-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis, which was reversed by blockade of AKT and Nrf2. Transplantation of CXCR7-EPCs accelerated endothelial repair and attenuated neointimal hyperplasia in diabetes mellitus more significantly than transplantation of diabetic or normal EPCs. However, the therapeutic effect of CXCR7-EPC transplantation on endothelial regeneration was reversed by knockdown of Nrf2 expression. Conclusions: Dysfunction of diabetic EPCs is associated with decreased CXCR7 expression. Furthermore, the SDF-1/CXCR7 axis positively regulates EPC function by activating the AKT/keap-1/Nrf2 axis. CXCR7-primed EPCs might be useful for endothelial regeneration in diabetes-associated vascular disease. [ABSTRACT FROM AUTHOR]

The Green materials zinc borate (ZB) and zinc silicate (ZS) were adopted as suppressants. Hartmann tube was used to study the flame inhibition effect of oil shale explosion. It showed that the flame front length became shorter and the propagation velocity and acceleration gradually decreased by increasing suppressants. When 30 wt% ZB was added, the complete inhibition of oil shale explosion flame could be achieved, while the flame inhibition effect of ZS was relatively weak. Flynn-Wall-Ozawa and Starink methods were used to study the activation energy of oil shale, which showed that the activation energy increased significantly after adding the suppressant. By characterization tests, the microstructure changes of oil shale before and after the explosion were analyzed, and the mechanism of the explosion inhibition difference between two suppressants was revealed. ZS played a physical inhibiting role by absorbing heat, reducing temperature and diluting the concentration of combustible gases. While ZB not only had the physical inhibition role of absorbing heat and diluting the concentration of gases, but also had a covering physical inhibition role. Simultaneously, ZB also had the chemical effect. It played a highly effective physical and chemical synergistic inhibition role in the deflagration of oil shale. • Zinc borate and zinc silicate were firstly applied in oil shale flame suppression. • Zinc borate has the better inhibition effect than zinc silicate. • The pyrolysis behavior of oil shale was studied thermodynamically. • The physical and chemical synergistic suppression mechanism of ZB was proposed. [ABSTRACT FROM AUTHOR]

Background: An outbreak of coronavirus disease 2019 (COVID-19) took place in Wuhan, China, by the end of 2019, and the disease continues to spread all over the world. The number of patients is increasing rapidly, a large number of infected patients is critically ill, and the mortality is high. However, information on COVID-19 patients is limited, and its clinical characteristics have not been fully studied. Objectives: To compare the performances of point-of-care lung ultrasound (LUS) and bedside chest X-ray in assessing the condition of COVID-19 patients with acute respiratory distress syndrome (ARDS). Methods: This observational study enrolled 42 COVID-19 patients with ARDS who were admitted to the Department of Critical Care Medicine of the Wuhan Union Hospital from February to April 2020. The point-of-care LUS characteristics of the COVID-19 patients with ARDS were summarized, and the performances of LUS and bedside chest X-ray in assessing the patient's condition were compared. Results: Most of the 42 patients were elderly individuals with chronic clinical diseases. The proportion of patients older than 60 years old was 85.7%. All patients were given invasive mechanical ventilation; eight (19.0%) of them received venovenous extracorporeal membrane oxygenation support. LUS has evident advantages in detecting lung consolidation, patchy shadows, and pleural thickening, and pleural line changes in particular. The receiver operating characteristic analysis indicated that the sensitivity, Youden index, and kappa value for detecting COVID-19 patients with ARDS were higher for LUS than the chest X-ray. Conclusion: LUS has better diagnostic accuracy and sensitivity in COVID-19 patients with ARDS than the chest X-ray. [ABSTRACT FROM AUTHOR]

Cecotrophy is a special behaviour of rabbits. Eating soft faeces can improve feed efficiency and maintain gut flora in rabbits. In our previous study, we found that fasting from soft faeces significantly reduced growth rate and total cholesterol (TC) in New Zealand white rabbits (NZW rabbits), thereby resulting in lower values for body weight and fat deposition in the soft faeces fasting group than in the control group. However, it has not been demonstrated whether cecotrophy by NZW rabbits can regulate lipid metabolism by changing the diversity of caecal microorganisms. In this study, thirty‐six 28‐day‐old weaned NZW female rabbits were randomly divided into two groups (the soft faeces fasting group and the control group) and fed to 90 days. Rabbits in the experimental group were treated with an Elizabeth circle to prevent them from eating their soft faeces. Then, the caecal contents of three rabbits from the soft faeces fasting group and three rabbits from the control group were collected for metagenomic sequencing. We found that the abundance of Bacteroides increased, while Ruminococcus decreased, compared with the control group after fasting from soft faeces. Relative abundance was depressed for genes related to metabolic pathways such as ascorbate and aldarate metabolism, riboflavin metabolism and bile secretion. Moreover, there was a general correlation between variation in microbial diversity and fat deposition. Bacteroides affects body weight and TC by participating in the riboflavin metabolism pathway. By investigating the effect of cecotrophy on caecal microorganisms of rabbits, we identified the key microorganisms that regulate the rapid growth performance of NZW rabbits, which may provide useful reference for the future research and development of microecological preparations for NZW rabbits. [ABSTRACT FROM AUTHOR]

Biofouling on surfaces of various materials has attracted considerable attention in biomedical and marine industries. Surface grafting based on covalent surface‐initiated polymerization offers a popular route to address this problem by providing diverse robust polymer coatings capable of preventing the biofouling in complex environments. However, the existing methods for synthesizing polymer coatings are complicated and rigorous, or require special catalysts, greatly limiting their practical applications. In this work, a radical‐cation‐based surface‐initiated polymerization protocol to graft the surface of darkened trans‐polyisoprene (TPI) rubber with a thermo‐responsive smart polymer, poly(N‐isopropylacrylamide) (PNIPAM), through a simple iodine doping process is reported. A series of characterizations were performed to provide adequate evidence to confirm the successful grafting. Combining the thermal sensitivity of PNIPAM with the photothermal conversion ability of the darkened rubber, efficient bacteria‐killing and antifouling capabilities were successfully achieved as a result of temperature‐controlled iodine release and switchable amphiphilicity of PNIPAM. Smart coatings: Radical cations are generated when rubber is exposed to iodine treatment. These radical cations not only facilitate photothermal conversion, but also initiate surface polymerization. A successful example of poly(N‐isopropylacrylamide) (PNIPAM) brushes grafted on darkened rubber demonstrates that the combination of thermoresponsive polymers with photothermal conversion opens a new avenue for exploiting light‐triggered bacteria‐killing and antifouling coatings. [ABSTRACT FROM AUTHOR]

Columbian coloration patterns in plumage are widespread phenomena in several standard breeds of poultry, such as the Columbian Plymouth Rock chicken. H line chicken plumage is generally a pure white except in the hackle, wing, and tail plumage, which coloration is very similar to the Columbian plumage pattern, but with the barring substituting for the black vertical striping. Thus, we refer to this plumage coloration as "sub-Columbian" pattern. However, the genetic basis of this phenotype remains unknown. Here, a F3 cross population between yellow plumage roosters and sub-Columbian plumage hens was constructed, for verifying sub-Columbian plumage was sex-linked dominant inheritance. To identify the candidate regions, F2 generation sub-Columbian plumage hens and yellow plumage hens with their parental lines were used for BSA-seq, and sub-Columbian plumage genes were mapped to a 10.46 Mb interval on chromosome Z. Remarkably, by transcriptome analysis of the neck and wing tip follicle tissues of the 2 plumage colors, we demonstrated that within the interval, only 1 gene, SLC45A2 expressed significant differently (P < 0.05). Through KASP, we identified L347M and A10331272T in solute carrier family 45 member 2 ( SLC45A2 ), and B2 haplotype of cyclin-dependent kinase inhibitor 2A ( CDKN2A ), showed near complete association with the phenotype. Eventually, we designed a hybridization experiment for verifying the locus of sub-Columbian plumage, which is inherited through Z-linked dominant inheritance and is controlled by SLC45A2 and CDKN2A. [ABSTRACT FROM AUTHOR]

• HMGB1 is a non-histone DNA-binding nuclear protein. • HMGB1 can actively secreted in the form of intracellular vesicles. • HMGB1 can also be released from necrotic cells or injured cells passively. • After binding with its receptors, HMGB1 trigger a series of biological effects. • HMGB1 was involved in the occurrence and development of asthma. High-mobility group box protein 1 (HMGB1) is a non-histone deoxyribonucleic acid-binding nuclear protein. In physiological state it is involved in gene transctioripn regulation and cell replication, differentiation and maturation. HMGB1 is actively secreted into the extracellular space in the form of intracellular vesicles, upon stimulation of inflammation and infection, by monocytes, macrophages, dendritic cells (DCs), and other immune cells, and can also be passively released by necrotic or injured cells. After binding with the corresponding receptors, HMGB1 can activate the downstream substrate and trigger a series of biological effects. HMGB1 was mainly dependent on toll-like re ceptors (TLR) 2 and 4, and receptors for advanced glycation end products (RAGE) to trigger intracellular signal transduction, and mediate innate and adoptive immune responses. Besides these, studies have reported the participation of TLR3, TLR9, T-cell immunoglobulin mucin (TIM) 3, CD24, anti-N-methyl-D-aspartate receptor (NMDAR) in Th2 inflammatory response, eosinophilic airway inflammation, and airway hyperresponsiveness, mediated by HMGB1 in asthma. Both clinical and experimental studies suggested that HMGB1 was involved in the pathogenesis of asthma probably by regulating the downstream signaling pathways via corresponding receptors. This article reviews the role of HMGB1 in pathogenesis of asthma, and provides a new theoretical basis for the diagnosis and treatment of asthma. [ABSTRACT FROM AUTHOR]

The Th (T helper) 2 response is characteristic of allergic asthma, and Th17 cells are involved in more severe asthma. Recent studies demonstrated that HMGB1 (High mobility group box 1 protein) regulates airway inflammation and the Th2, Th17 inflammatory response in asthma. HMGB1 can interact with Toll-like receptors (TLR) 2 and 4, and the receptor for advanced glycation end products (RAGE), activating the NF-κB (nuclear factor kappa B) signaling pathway and inducing the release of downstream inflammatory mediators. Both Th cells and dendritic cells express TLR2, TLR4, and RAGE receptors. Therefore, we speculate that HMGB1 could regulate the differentiation of Th2, Th17 cells in asthma through direct and indirect mechanisms. An ovalbumin (OVA)-induced mouse asthmatic model was established. Anti-HMGB1 antibody or rHMGB1 was administered to OVA-sensitized mice 30 min prior to each challenge. For in vitro studies, magnetically separated CD4 + naive T cells were stimulated with or without rHMGB1 and/or anti-HMGB1 antibody. BMDCs (bone marrow-derived dendritic cells)-stimulated with or without rHMGB1 and/or anti-HMGB1 antibody were cocultured with CD4 + naive T cells. Our study showed that administration of rHMGB1 aggravated airway inflammation and mucus production, and induced Th2, Th17 polarization in asthmatic mice, and that anti-HMGB1 antibody weakened characteristic features of asthma and blocked the Th2, Th17 inflammatory responses. HMGB1 could directly act on naive T cells to induce differentiation of Th2, Th17 cells in vitro through activating the TLR2, TLR4, RAGE-NF-κB signal pathway in CD4 + naive T cells. HMGB1 could also indirectly promote Th2, Th17 differentiation via activating the TLR2, TLR4, RAGE-NF-κB signal pathway in DCs to mediate their maturation and antigen-presenting ability in vitro . [ABSTRACT FROM AUTHOR]

The ATP/P2X7 axis of dendritic cells (DCs) mediates the activation of NLRP3 inflammasome and promotes secretion of interleukin (IL)−1β and IL-18 to induce T helper (Th) 2, Th17 differentiation in the pathogenesis of asthma. NLRP3 inflammasome also regulates high mobility protein 1 (HMGB1) release in DCs. Recent studies demonstrated the correlation between HMGB1 expression and airway inflammation and hyper-responsiveness (AHR) in asthma. However, the relationship between the ATP/P2X7-NLRP3 axis and HMGB1 in DCs in asthma is still unclear. ATP, apyrase, Brilliant Blue G, BzATP, glibenclamide, and Z-YVAD-FMK were administered to ovalbumin (OVA)-induced murine asthmatic model. For in vitro studies, bone marrow-derived mononuclear cells (BMDCs) were primed with LPS and stimulated with the same reagents. Activation of the ATP/P2X7 axis aggravated airway inflammation and AHR in the lung and induced Th2, Th17 polarization in asthmatic mice. Inhibition of NLRP3 inflammasome weakened cardinal features of asthma and blocked Th2, Th17 polarization. In vitro and vivo, ATP/P2X7 axis activated NLRP3 inflammasome and induced HMGB1 expression and release from DCs. Inhibition of NLRP3 inflammasome reduced HMGB1 expression and release. The ATP/P2X7-NLRP3 axis of DCs participates in mediating airway inflammation, AHR, and promoting Th2, Th17 inflammatory responses in asthmatic mice by inducing HMGB1 expression and secretion. [ABSTRACT FROM AUTHOR]

Organic conjugated polymers with low energy bandgaps are emerging as a particular class of near-infrared (NIR) photothermal conversion materials. However, these polymers routinely possess high phase transition temperatures due to the rigid skeleton and strong intermolecular interactions. Conjugated polymers can rarely be thermally processed at low temperature, especially below 100 °C. This work formulates a concept of post-darkening modeling production ( p-DMP) by which the thermoplastic non-conjugated trans-polyisoprene (TPI) is refreshed into a photothermal conversion material with high light use efficiency. Two steps, including the customizable shaping at low temperature and iodine vapor-tailored 'darkening', ensure the ease of preparing photothermal conversion devices with desirable topologies. A few characterizations, with the combination of density functional theory (DFT) calculations, provide reasonable explanations for understanding the 'darkening' process of TPI in iodine atmosphere. In particular, the p-DMP is successfully extended to three-dimension (3D) printing, opening an avenue to fabricate personalized photothermal products, for example, a sunlight-directed physiotherapy device for healthcare of articular tissues. [ABSTRACT FROM AUTHOR]

Transcription factor 3 (TCF3) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family. Recent studies have demonstrated its potential carcinogenic properties. Here we show that TCF3 was upregulated in glioma tissues compared with normal brain tissues. This upregulation of the TCF3 gene probably has functional significance in brain-tumor progression. Our studies on glioblastoma multiforme (GBM) cell lines show that knock-down of TCF3 induced apoptosis and inhibited cell migration. Further analysis revealed that down-regulation of TCF3 gene expression inhibits Akt and Erk1/2 activation, suggesting that the carcinogenic properties of TCF3 in GBM are partially mediated by the phosphatidylinositol 3-kinase-Akt and MAPK-Erk signaling pathways. Considered together, the results of this study demonstrate that high levels of TCF3 in gliomas potentially promote glioma development through the Akt and Erk pathways. [ABSTRACT FROM AUTHOR]

Branched-chain amino acids (BCAAs) and branched-chain α-keto acids (BCKAs) play significant biological roles as they are involved in protein and neurotransmitter synthesis as well as energy metabolism pathways. To routinely and accurately study the dynamics of BCAAs and BCKAs in human diseases, e.g. cerebral infarction, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated. The plasma samples were deproteinized with acetonitrile, and then separated on a reversed phase C18 column with a mobile phase of 0.1 % formic acid (solvent A)-methanol (solvent B) using gradient elution. The detection of BCAAs and BCKAs was conducted in multiple reaction monitoring with positive/negative electrospray ionization switching mode. Biologically relevant isomers such as leucine and isoleucine were individually quantified by combining chromatographic separation and fragmentation. Good linearity ( R > 0.99) was obtained for all six analytes with the limits of detection from 0.1 to 0.2 µg/mL. The intra-day and inter-day accuracy ranged from 93.7 to 108.4 % and the relative standard deviation (RSD) did not exceed 15.0 %. The recovery was more than 80 % with RSD less than 14.0 %. The main improvements compared to related, state-of-the-art methods included enhanced sensitivity, enhanced separation of isomers, and reduced complexity of sample processing. Finally, the validated method was applied to analyze the plasma samples of healthy volunteers and patients suffering cerebral infarction, and significant differences in the concentration levels of BCAAs and BCKAs were observed. [ABSTRACT FROM AUTHOR]

• The suitable cooking methods of Tan sheep for different population was analyzed. • Species and numbers of lipids among raw and processed Tan sheep were compared. • Lipid metabolism in thermal processing was explored by lipidomics and HRMS. • Chemical changes of PC, LPC, SM and Cer were detected. • The 90 lipids in 6 classes with significant difference were quantified. Thermal processing affects the lipid compositions of meat products. The study determined the effects of boiled, steamed and roasted processing methods on the lipidomics profiles of Tan sheep meat with a validated UPLC-Q-Orbitrap HRMS combined lipid screening strategy method. Combined with sphingolipid metabolism, the boiled approach was the suitable choice for atherosclerosis patients for more losses of sphingomyelin than ceramide in meat. The similarly less losses of phosphatidylcholine and lysophosphatidylcholine showed in glycerophospholipid metabolism implied that steamed Tan sheep meat was more suitable for the populations of elderly and infants. Furthermore, a total of 90 lipids with significant difference (VIP > 1) in 6 lipid subclasses (sphingomyelin, ceramide, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamines, triacylglycerol,) were quantified among raw and three types of thermal processed Tan sheep meat, further providing useful information for identification of meat products with different thermal processing methods (LOD with 0.14–0.31 μg kg−1, LOQ with 0.39–0.90 μg kg−1). [ABSTRACT FROM AUTHOR]

Cold chain (−20 °C) is one of the main transportation methods for storage of Tan sheep products. Lipids (66) in seven subclasses involved in sphingolipid, glycerophospholipid and fatty acid degradation metabolism were quantified in Tan sheep under cold chain storage, including fatty acyl carnitines, phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), ceramides, sphingomyelin (SM) and lysophosphatidylethanolamine (LPE). Lipid transformation and molecular mechanism analyzed using fragmentation mechanisms and UHPLC-Q-Orbitrap MS/MS combined with lipidomics approaches determined transient increases of certain PC, PE and fatty acyl carnitine during the first 12 days of cold storage, subsequent declines of SM, PC, PE and fatty acyl carnitine, as well as increases of ceramide, LPC and LPE (24 days). These results offered insights into lipid transformation and quality of Tan sheep during cold chain storage. [ABSTRACT FROM AUTHOR]

Deeply understanding the virus-host interaction is a prerequisite for developing effective anti-viral strategies. Traditionally, the transporter associated with antigen processing type 1 (TAP1) is critical for antigen presentation to regulate adaptive immunity. However, its role in controlling viral infections through modulating innate immune signaling is not yet fully understood. In the present study, we reported that TAP1, as a product of interferon-stimulated genes (ISGs), had broadly antiviral activity against various viruses such as herpes simplex virus 1 (HSV-1), adenoviruses (AdV), vesicular stomatitis virus (VSV), dengue virus (DENV), Zika virus (ZIKV), and influenza virus (PR8) etc. This antiviral activity by TAP1 was further confirmed by series of loss-of-function and gain-of-function experiments. Our further investigation revealed that TAP1 significantly promoted the interferon (IFN)-β production through activating the TANK binding kinase-1 (TBK1) and the interferon regulatory factor 3 (IRF3) signaling transduction. Our work highlighted the broadly anti-viral function of TAP1 by modulating innate immunity, which is independent of its well-known function of antigen presentation. This study will provide insights into developing novel vaccination and immunotherapy strategies against emerging infectious diseases. [ABSTRACT FROM AUTHOR]

• A unique acorn leaf-like CdS/MoS 2 catalysts were successfully synthesized via hydrothermal method. • The hydrogen production performance of CdS/MoS 2 reached 70.05 mmol·g−1·h−1, which is 330 times higher than the pristine CdS. • A series of investigations were conducted to reveal the mechanism. Photocatalytic hydrogen production through water splitting is an appealing technology to alleviate the escalating fossil fuel energy crisis. The advancement of visible-light-driven hydrogen production systems is a crucial aspect of hydrogen research. In this study, we successfully synthesized a unique acorn leaf-like CdS/MoS 2 material via a hydrothermal method, with layered deposited MoS 2 nanosheets, for driving hydrogen generation under illumination. By systematically varying the sodium molybdate concentration, we looked into how the MoS 2 affected the optical properties and photocatalytic performance of the acorn-leaf-like CdS/MoS 2. Under illumination, the photocatalytic hydrogen production performance of the acorn leaf-like CdS/MoS 2 reached 70.05 mmol·g−1·h−1 (at a catalyst dosage of 10 mg), which is approximately 330 times higher than the unmodified CdS original material. It was determined that the apparent quantum yield at 450 nm was 2.104 %, corresponding to a solar-to-hydrogen conversion efficiency of 9.383 %. Mechanistic investigations revealed that MoS 2 nanosheets function as co-catalysts and electron acceptors, effectively promoting electron transfer and the separation of photogenerated charge carriers from CdS, thereby consequently enhancing the kinetics of surface hydrogen evolution. This work offers valuable insights into the development of efficient photocatalysts with anti-photocorrosion properties for sustainable hydrogen production. [ABSTRACT FROM AUTHOR]

Aims: To assess the effects of plerixafor on function and endothelial regeneration of endothelial progenitor cells (EPCs).Methods: The proliferation and adhesion capacity of EPCs were evaluated in vitro. Furthermore, the expression levels of CXC chemokine receptor-7 (CXCR7) were detected before and after treatment with plerixafor. The CXCR7 expression of EPCs was knocked-down by RNA interference to evaluate the role of CXCR7 in regulating function of EPCs. A rat carotid artery injury model was established to assess the influences of plerixafor on endothelial regeneration.Results: Plerixafor stimulated adhesion capacity of EPCs, associating with upregulation of CXCR7 and activation of LFA-1 and VLA-4 molecules. Knockdown of CXCR7 slightly impaired proliferation capacity but significantly attenuated adhesion capacity of EPCs. Plerixafor facilitated endothelial repair at 7 days, while reduced neointimal hyperplasia at 7 and 14 days via recruiting more EPCs participating in endothelial reparation.Conclusions: Plerixafor can positively regulate adhesion capacity of EPCs to HUVECs via elevating the expression level of CXCR7 and stimulating LFA-1 and VLA-4 molecules activation. Treatment with plerixafor accelerated re-endothelialization and inhibited neointimal hyperplasia after endoth elial injury, indicating that it can to be used for endothelial regeneration. [ABSTRACT FROM AUTHOR]

• HMGB1 aggravates acute lung injury by suppressing immunosuppressive function of Tregs. • HMGB1 reduces the number and activity of Tregs. • HMGB1 reduces the secretion of anti-inflammatory cytokines (IL-10, TGF-β) from Tregs. • Tregs stimulated by HMGB1 regulate the macrophage polarization, as well as the proinflammatory response of macrophages. CD4+CD25+FoxP3+ T helper cells (Tregs), a subgroup of CD4+ T helper cells, are critical effectors that protect against acute lung injury (ALI) by contact-dependent suppression or releasing anti-inflammatory cytokines including interleukin-10 (IL-10), and transforming growth factor (TGF-β). HMGB1 (High mobility group box 1 protein) was identified as a nuclear non-histone DNA-binding chromosomal protein, which participates in the regulation of lung inflammatory response and pathological processes in ALI. Previous studies have suggested that Tregs overexpresses the HMGB1-recognizing receptor. However, the interaction of HMGB1 with Tregs in ALI is still unclear. To investigate whether HMGB1 aggravates ALI by suppressing immunosuppressive function of Tregs. Anti-HMGB1 antibody and recombinant mouse HMGB1 (rHMGB1) were administered in lipopolysaccharide (LPS)-induced ALI mice and polarized LPS-primed Tregs in vitro. The Tregs pre-stimulated with or without rHMGB1 were adoptively transferred to ALI mice and depleted by Diphtheria toxin (DT). For coculture experiment, isolated Tregs were first pre-stimulated with or without rHMGB1 or anti-HMGB1 antibody, then they were cocultured with bone marrow-derived macrophages (BMMs) under LPS stimulation. Tregs protected against acute lung pathological injury. HMGB1 modulated the suppressive function of Tregs as follows: reduction in the number of the cells and the activity of Tregs, the secretion of anti-inflammatory cytokines (IL-10, TGF-β) from Tregs, the production of IL-2 from CD4+ T cells and CD11c+ DCs, and the M2 polarization of macrophages, as well as inducing proinflammatory response of macrophages. HMGB1 could aggravate LPS induced-ALI through suppressing the activity and function of Tregs. [ABSTRACT FROM AUTHOR]

High-mobility group box 1 protein (HMGB1) is a crucial proinflammatory cytokine that contributes to acute lung injury (ALI). Macrophages are known to express the primary receptors (Toll-like receptor [TLR] 2, and TLR4) of HMGB1 for transmitting intracellular signals. Studies have revealed that double-stranded RNA activated protein kinase R (PKR), which is expressed in macrophages, participates in ALI by regulating macrophage polarization and proinflammatory cytokine release, and that PKR is normally activated by a subset of TLRs. The present study investigated whether HMGB1 engages in ALI by activating PKR in macrophages and inducing classically activated macrophage (M1) polarization via TLR2- and TLR4-mediated nuclear factor (NF)-κB signaling pathways. In an vivo mouse model of lipopolysaccharide (LPS)-induced ALI, anti-HMGB1, rHMGB1, LPS-RS (TLR2 and TLR4 antagonist), or C16 (PKR inhibitor) was administered to mice 2 h after LPS challenge or 1 h before LPS challenge. In vitro, bone marrow-derived macrophages from mice primed with LPS were stimulated with or without anti-HMGB1, rHMGB1, LPS-RS, or C16. Our studies revealed that rHMGB1 stimulation induced M1 polarization in ALI, and that anti-HMGB1 and C16 treatments had the opposite effect. Anti-HMGB1 and LPS-RS significantly inhibited LPS-induced PKR expression in macrophages; however, rHMGB1 administration increased PKR expression. These results indicate that HMGB1 participates in the pathogenesis of ALI by activating PKR in macrophages and inducing M1 polarization through TLR2- and TLR4-mediated NF-κB signaling pathways. • HMGB1 induces M1 polarization in LPS-induced ALI. • HMGB1 activates PKR in macrophages. • Inhibition of TLR2 and TLR4 weakens the activation of PKR in macrophages. • Inhibition of PKR attenuates M1 polarization. [ABSTRACT FROM AUTHOR]

Recent studies revealed that macrophages are polarized towards the M2 phenotype in an ovalbumin (OVA)-induced asthmatic model. Alveolar macrophages (AMs) are immune barriers in alveoli to various pathogens in the respiratory tract; AMs suppress Th2 cell proliferation, inhibit interleukin (IL)-4, IL-5, and IL-13 secretion, and protect against airway hyperresponsiveness in allergic asthma. However, the polarization status and effects of different types of AMs in the pathogenesis of asthma are not known. ATP/P2X7r, expressed mainly on macrophages and dendritic cells, is associated with acute and chronic asthmatic airway inflammation and Th2 immune responses in mice and humans and functions by activating the NLRP3 inflammasome complex and inducing proinflammatory cytokine release (IL-1β and IL-18). Therefore, we evaluated the association between the ATP/P2X7r axis and different types of AMs in the pathology of allergic asthma. A murine AM-depleted asthma model was established by administration of clodronate-encapsulated liposomes, and M1-or M2-AMs were adoptively transferred to confirm the effects of different AMs in allergic asthma. Brilliant Blue G and BzATP were administered to OVA/HDM-induced mice in vivo. Lipopolysaccharide + OVA, ATP, Brilliant Blue G, and BzATP were used to stimulate AMs isolated from control and asthmatic mice. We found that selective depletion of AMs aggravated lung inflammation in asthmatic mice. Further, M2-type AMs may play a key role in mediating asthmatic inflammatory responses via the adoptive transfer of M2-type AMs to AM-depleted asthmatic mice, and the phenotype of AMs differentiated to M2 type in asthma. P2X7r expression in M2-type AMs was higher than that in M1-type AMs. Activating P2X7r induced polarization of M2-type AMs and inhibited polarization of M1-type AMs, while blockage of P2X7r had the opposite effect. The ATP/P2X7r axis may participate in the pathogenesis of asthma by mediating the M2-type AM polarization. • M2-type AMs activate Th2 cell inflammatory response in allergic asthma. • The AM phenotype switches to M2 type in an OVA-induced asthmatic mice model. • M2-type alveolar macrophages preferentially express P2X7r. • The ATP/P2X7r axis induces M2-type and inhibits M1-type polarization of AMs. [ABSTRACT FROM AUTHOR]

Background: The global status of the COVID-19 pandemic is not optimistic. This is a particularly vulnerable time for patients with pre-existing headache disorders. The present study aimed to investigate the impact of the COVID-19 pandemic on headache patients in China.Methods: A survey was conducted through an online survey platform on June 6, 2020. Demographic characteristics, the PHQ-9, the ISI, a COVID-19 questionnaire and a headache profile survey were included in the online questionnaire.Results: Eventually, a total of 15,000 participants from China completed the online questionnaire. Among them, 2806 participants had pre-existing headache disorders. Our analysis showed reductions in the duration of headaches (3.414 ± 6.859 vs 4.033 ± 7.325 h, P<0.001), number of headache days per month (1.788 ± 2.989 vs 2.092 ± 3.694, P<0.001), and headache intensity (4.110 ± 1.609 vs 4.290 ± 1.680, P<0.001) during the COVID-19 pandemic. Smoking (OR = 1.397, 95% CI 1.090 to 1.790, P = 0.008) and getting support from family members during social isolation (OR = 1.656, 95% CI 1.075 to 2.550, P = 0.022) were independent factors affecting the reduction in the duration of headaches. Education level (OR = 1.478, 95% CI 1.103 to 1.980, P = 0.009) and having a relative or acquaintance who contracted COVID-19 (OR = 0.643, 95% CI 0.458 to 0.902, P = 0.011) were the independent factors affecting the reduction in headache severity. Living in the Wuhan area, having symptoms or a diagnosis of COVID-19 and having relatives or acquaintances who had contracted COVID-19 were associated with the worsening of headaches.Conclusions: Participants experienced an overall trend towards the improvement of headaches during the COVID-19 pandemic. Family support might play an important role in the improvement of headaches. [ABSTRACT FROM AUTHOR]

Introduction: Cefazolin is the leading antibiotic used to prevent surgical site infections worldwide. Consensus guidelines recommend adjustment of the cefazolin dose above and below 120 kg without regard to body composition. Algorithms exist to repurpose radiologic data into body composition (morphomics) and inform dosing decisions in obesity. Objectives: To compare the current standard of body weight to morphomic measurements as covariates of cefazolin pharmacokinetics and aid dose stratification of cefazolin in patients with obesity undergoing colorectal surgery. Methods: This prospective study measured cefazolin plasma, fat, and colon tissue concentrations in colorectal surgery patients in order to develop a morphomics‐informed population pharmacokinetic (PopPK) model to guide dose adjustments. A physiologically‐based pharmacokinetic (PBPK) model was also constructed to inform tissue partitioning in morbidly obese patients (n = 21, body mass index ≥35 kg/m2 with one or more co‐morbid conditions). Results: Morphomics and pharmacokinetic data were available in 58 patients with a median [min, max] weight and age of 95.9 [68.5, 148.8] kg and 55 [25, 79] years, respectively. The plasma‐to‐subcutaneous fat partition coefficient was predicted to be 0.072 and 0.060 by the PopPK and PBPK models, respectively. The estimated creatinine clearance (eCLcr) and body depth at the third lumbar vertebra (body depth_L3) were identified as covariates of cefazolin exposure. The probability of maintaining subcutaneous fat concentrations above 2 μg/mL for 100% of a 4‐h surgical period was below 90% when eCLcr ≥105 mL/min and body depth_L3 ≥ 300 mm and less sensitive to the rate of infusion between 5 and 60 min. Conclusions: Kidney function and morphomics were more informative than body weight as covariates of cefazolin target site exposure. Data from more diverse populations, consensus on target cefazolin exposure, and comparative studies are needed before a change in practice can be implemented. [ABSTRACT FROM AUTHOR]

The integration of high mechanical toughness, impact strength as well as excellent flame-retardant properties toward epoxy resins (EPs) have always been a dilemma. The inadequate overall performance of EPs severely restricts their sustainable utilization in engineering aspects over long-term. Herein, a new bio-based agent (diglycidyl ether of magnolol phosphine oxide, referred as DGEMP) derived from magnolol (classified as lignan), extracted from natural plants Magnolia officinalis, was successfully synthesized and further employed as a flame-retardant reactive additive to diglycidyl ether of bisphenol A (DGEBA). As demonstration, the composite resin, DGEBA/15DGEMP (15 wt% DGEMP), achieved an Underwriters Laboratories-94 V-0 rating with a high limiting oxygen index (LOI) value (41.5%). In cone calorimeter tests, it showed that heat release and smoke production were effectively inhibited during combustion, wherein the peak heat release rate (PHRR) value of DGEBA/15DGEMP was reduced by 50% compared to neat DGEBA. Additionally, it exhibited a superior tensile strength (82.8 MPa), toughness (5.11 MJ/m3) and impact strength (36.5 kJ/m2), much higher than that of neat DGEBA (49.7 MPa, 2.05 MJ/m3 and 20.9 kJ/m2). Thus, it is highly anticipated that DGEMP imparts significantly improved mechanical and fire-retarded properties to conventional EPs, which holds a great potential to address the pressing challenges in EP thermosets industry. [ABSTRACT FROM AUTHOR]

• THRIL knockdown alleviated CLP-induced lung injury in mice. • THRIL knockdown alleviated CLP-induced inflammatory response of lung in mice. • THRIL knockdown inhibited LPS-induced inflammatory responses and apoptosis in MPVECs. • THRIL directly targets miR-424. • THRIL competitively binds miR-424 to up-regulate ROCK2. Here, we aimed to investigate the role of long noncoding RNA (lncRNA) THRIL in septic-induced acute lung injury. C57BL/6 mice were injected with Adenoviruses (Ad)-shTHRIL or negative control (NC) before caecal ligation and puncture (CLP) operation. MPVECs were transfected with Ad-shTHRIL or NC, followed by lipopolysaccharide (LPS) treatment. MiR-424 and Rho-associated kinase 2 (ROCK2) were predicted and verified as direct targets of THRIL and miR-424, respectively, by using dual-luciferase reporter assay. ROCK2 overexpression vector and shTHRIL were co-transfected into mouse pulmonary microvascular endothelial cells for 24 h before LPS treatment. Our results showed that THRIL was highly expressed in the lung of sepsis mice. CLP triggered severe lung injury and apoptosis in mice, which was abolished by THRIL knockdown. Moreover, CLP treatment visibly increased protein concentration, the number of total cell of neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF). Besides, elevated protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 were observed in both lung and BALF. However, inhibition of THRIL reduced the number of inflammatory cells and the production of pro-inflammatory cytokines in sepsis mouse model. The effect of THRIL on inflammatory response and apoptosis in the lung was confirmed in sepsis cell model. Moreover, mechanistic studies have shown that THRIL up-regulated ROCK2 level through sponging miR-424. Furthermore, ROCK2 overexpression reversed the inhibitory effects of THRIL knockdown on LPS-induced inflammatory response and apoptosis. Overall, in vivo and in vitro results suggested that THRIL accelerates sepsis-induced lung injury by sponging miR-424 and further restoring ROCK2. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chinese mutton ham is a dry‐cured meat product with a long ripening time. The aim of this study was to identify and characterize antioxidant peptides from Chinese mutton ham. RESULTS: Mutton ham peptides (MHPs) were purified by gel filtration, anion exchange and reversed‐phase high‐performance liquid chromatography steps. The 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt (ABTS) free radical scavenging capacity was used to guide the purification of MHPs. Three antioxidant peptides were identified by liquid chromatography with tandem mass spectrometry (LC–MS/MS) as Met‐Trp‐Thr‐Asp (MWTD), Ala‐Pro‐Tyr‐Met‐Met (APYMM) and Phe‐Trp‐Ile‐Ile‐Glu (FWIIE), with molecular weights 551.61, 611.76, and 706.84 Da, respectively. Among them, APYMM exhibited the highest ABTS radical scavenging activity. The three peptides had the ability to inhibit lipid oxidation and Fenton's reagent‐induced protein oxidation and DNA damage. After simulated gastrointestinal digestion, FWIIE and APYMM showed increased antioxidant activity, while MWTD showed decreased activity. CONCLUSION: Three novel peptides isolated from Chinese mutton ham had strong biological activity. Chinese mutton ham is potentially a functional food and an excellent source of natural antioxidants. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Photothermal materials (PTMs) have been intensively investigated in the fields of photothermal conversion. Superior to solid PTMs, liquid PTMs are leading the trends in satisfying the demands of high flexibility and easy recycling. Successful examples of liquid PTMs are mostly formulated by dispersing solid PTMs in solvents, but suffer from the problems of phase segregation and solvent pollution. In this work, a low‐cost formulation is proposed, which involves an oxidative product of ethyl oleate by iodine. It is an intrinsic liquid PTM, preserving the fluidic nature as well as possessing considerable ability for photothermal conversion. In addition to understanding the mechanism of light absorption in the visible and even near infrared windows, two examples are presented to demonstrate the great potential of liquid PTMs in broad areas such as light sensing and energy storage. [ABSTRACT FROM AUTHOR]

Glutaminolysis is the metabolic pathway that lyses glutamine to glutamate, alanine, citrate, aspartate, and so on. As partially recruiting reaction steps from the tricarboxylic acid (TCA) cycle and the malate-aspartate shuttle, glutaminolysis takes essential place in physiological and pathological situations. We herein developed a sensitive, rapid, and reproducible liquid chromatography-tandem mass spectrometry method to determine the perturbation of glutaminolysis in human plasma by quantifying 13 involved metabolites in a single 20-min run. A pHILIC column with a gradient elution system consisting of acetonitrile-5 mM ammonium acetate was used for separation, while an electrospray ionization source (ESI) operated in negative mode with multiple reaction monitoring was employed for detection. The method was fully validated according to FDA's guidelines, and it generally provided good results in terms of linearity (the correlation coefficient no less than 0.9911 within the range of 0.05–800 μg/mL), intra- and inter-day precision (less than 18.38%) and accuracy (relative standard deviation between 89.24 and 113.4%), with lower limits of quantification between 0.05 and 10 μg/mL. The new analytical approach was successfully applied to analyze the plasma samples from 38 healthy volunteers and 34 patients with type 2 diabetes (T2D). Based on the great sensitivity and comprehensive capacity, the targeted analysis revealed the imperceptible abnormalities in the concentrations of key intermediates, such as iso-citrate and cis-aconitate, thus allowing us to obtain a thorough understanding of glutaminolysis disorder during T2D. Graphical abstract ᅟ [ABSTRACT FROM AUTHOR]

Abstract: Decomposition and repolymerization of conjugated polymers offer great promise for developing recyclable photothermal conversion materials, which yet remain challenging. Herein, a crosslinked conjugated polymer based on a dynamic covalent bond of Schiff base is developed. This polymer possesses photothermal conversion efficiency as high as 90.4 %. Decomposition of the polymer under specialized conditions is corroborated by various characterizations. The kinetics study is also investigated to understand this degradation process. Furthermore, those decomposed species can be repolymerized back to conjugated polymers which possess the same photothermal conversion efficiency as the pristine polymer. Such a degradable and recyclable photothermal polymer is successfully used as a heat source for photothermal‐electrical conversion to generate Seebeck voltage under either near infrared (NIR) irradiation or solar illumination. [ABSTRACT FROM AUTHOR]

Anhedonia is an important aspect of adolescent-onset major depressive disorder (MDD) and is associated with increased risk of suicidal behaviors and poor treatment outcomes. However, the neural circuitry underlying this deficit has not been well defined. This study aims to identify the relationships between anhedonia and changes in static and dynamic functional connectivity (FC) in adolescent-onset MDD patients compared with healthy control subjects (HCs) and adult-onset MDD patients. A total of 157 participants completed the Snaith-Hamilton Pleasure Scale (SHAPS) to assess hedonic capacity. Resting-state functional imaging scans were analysed using graph theoretical analysis, network-based statistics (NBS) and sliding window correlation analysis to explore the potential patterns of neural network brain disruptions in adolescent-onset MDD. Pearson correlations and support vector machines regression (SVR) were used to explore correlations and predict network measures with SHAPS scores. Compared with those with adult-onset MDD, adolescent-onset MDD patients showed decreased FC in 7 nodes and 6 connections, with the right angular gyrus (AG), left AG and left paracentral lobule having the largest number of connected edges (P = 0.0396, NBS-corrected). Their average FC and SHAPS scores were positively correlated (r = 0.309, P = 0.035). Regarding dynamic FC, compared with HCs, adolescent-onset MDD patients showed a tendency towards a decreased frequency in moderate-intensity brain FC states (P = 0.014), which was significantly and positively correlated with SHAPS scores (r = 0.425, P = 0.003). SVR also revealed AG-centred FC and dynamic FC could predict SHAPS scores (MSE = 27.233, P = 0.001). These findings provide distinct evidence on the physiological mechanisms of adolescent-onset MDD and anhedonia. • Angular gyrus centred functional connectivity change in adolescent-onset depressed. • Moderate-intensity brain functional connectivity change in early-onset depressed. • Static and dynamic functional connectivity predict anhedonia. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS), a prevalent cause of admittance to intensive care units, is associated with high mortality. Prone positioning has been proven to improve the outcomes of moderate to severe ARDS patients owing to its physiological effects. Venovenous extracorporeal membrane oxygenation (VV ECMO) will be considered in patients with severe hypoxemia. However, for patients with severe hypoxemia supported with VV ECMO, the potential effects and optimal strategies of prone positioning remain unclear. This review aimed to present these controversial questions and highlight directions for future research. Main body: The clinically significant benefit of prone positioning and early VV ECMO alone was confirmed in patients with severe ARDS. However, a number of questions regarding the combination of VV ECMO and prone positioning remain unanswered. We discussed the potential effects of prone positioning on gas exchange, respiratory mechanics, hemodynamics, and outcomes. Strategies to achieve optimal outcomes, including indications, timing, duration, and frequency of prone positioning, as well as the management of respiratory drive during prone positioning sessions in ARDS patients receiving VV ECMO, are challenging and controversial. Additionally, whether and how to implement prone positioning according to ARDS phenotypes should be evaluated. Lung morphology monitored by computed tomography, lung ultrasound, or electrical impedance tomography might be a potential indication to make an individualized plan for prone positioning therapy in patients supported with VV ECMO. Conclusion: For patients with ARDS supported with VV ECMO, the potential effects of prone positioning have yet to be clarified. Ensuring an optimal strategy, especially an individualized plan for prone positioning therapy during VV ECMO, is particularly challenging and requires further research. [ABSTRACT FROM AUTHOR]

To unlock the widespread use of block copolymers as photonic pigments, there is an urgent need to consider their environmental impact (cf. microplastic pollution). Here we show how an inverse photonic glass architecture can enable the use of biocompatible bottlebrush block copolymers (BBCPs), which otherwise lack the refractive index contrast needed for a strong photonic response. A library of photonic pigments is produced from poly(norbornene‐graft‐polycaprolactone)‐block‐poly(norbornene‐graft‐polyethylene glycol), with the color tuned via either the BBCP molecular weight or the processing temperature upon microparticle fabrication. The structure–optic relationship between the 3D porous morphology of the microparticles and their complex optical response is revealed by both an analytical scattering model and 3D finite‐difference time domain (FDTD) simulations. Combined, this allows for strategies to enhance the color purity to be proposed and realized with our biocompatible BBCP system. [ABSTRACT FROM AUTHOR]

To unlock the widespread use of block copolymers as photonic pigments, there is an urgent need to consider their environmental impact (cf. microplastic pollution). Here we show how an inverse photonic glass architecture can enable the use of biocompatible bottlebrush block copolymers (BBCPs), which otherwise lack the refractive index contrast needed for a strong photonic response. A library of photonic pigments is produced from poly(norbornene‐graft‐polycaprolactone)‐block‐poly(norbornene‐graft‐polyethylene glycol), with the color tuned via either the BBCP molecular weight or the processing temperature upon microparticle fabrication. The structure–optic relationship between the 3D porous morphology of the microparticles and their complex optical response is revealed by both an analytical scattering model and 3D finite‐difference time domain (FDTD) simulations. Combined, this allows for strategies to enhance the color purity to be proposed and realized with our biocompatible BBCP system. [ABSTRACT FROM AUTHOR]

Background: Mental health problems are becoming increasingly common among college students, including depression, anxiety and sleep disturbances, which can affect their daily life and learning and even lead to suicide. The purpose of this study was to explore the gender differences in mental health symptoms among Chinese college students.Methods: The study population included 29,099 college students. All participants were assessed with the Patient Health Questionnaire-9 (PHQ-9), the 7-item Generalized Anxiety Disorder Scale (GAD-7), the Insomnia Severity Index (ISI), and the Suicidal Behaviors Questionnaire-Revised (SBQ-R). We assessed and compared network and centrality in females and males separately, as well as students with suicidal ideation.Results: Satisfaction with current sleep pattern (I4), worry about different things (A3) and irritable (A6) appeared to be the most central symptoms in the female network. In the male network, satisfaction with current sleep pattern (I4), tired or little energy (D4) and feeling down, hopeless (D2) were the most central symptoms. In both suicidal ideation networks, the top five central symptoms included four anxiety symptoms and one sleep symptom.Limitations: This study used cross-sectional data and could not examine the dynamic relationship between symptoms.Conclusion: There were gender differences in college students' mental health network. In addition to poor quality sleep, the central symptoms of the female network were anxiety symptoms, while those of the male were mainly depression symptoms. There were no gender difference in the suicidal ideation network and the central symptoms were anxiety symptoms and difficulty falling asleep. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the antigen-presenting cells that initiate and direct adaptive immune responses, and thus are critically important in vaccine design. Although DC-targeting vaccines have attracted attention, relevant studies on chicken are rare. A high diversity T7 phage display nanobody library was constructed for bio-panning of intact chicken bone marrow DCs to find DC-specific binding nanobodies. After three rounds of screening, 46 unique sequence phage clones were identified from 125 randomly selected phage clones. Several DC-binding phage clones were selected using the specificity assay. Phage-54, -74, -16 and -121 bound not only with chicken DCs, but also with duck and goose DCs. In vitro, confocal microscopy observation demonstrated that phage-54 and phage-74 efficiently adsorbed onto DCs within 15 min compared to T7-wt. The pull-down assay, however, did not detect any of the previously reported proteins for chicken DCs that could have interacted with the nanobodies displayed on phage-54 and phage-74. Nonetheless, Specified pathogen-free chickens immunized with phage-54 and phage-74 displayed higher levels of anti-p10 antibody than the T7-wt, indicating enhanced antibody production by nanobody mediated-DC targeting. Therefore, this study identified two avian (chicken, duck and goose) DC-specific binding nanobodies, which may be used for the development of DC-targeting vaccines. [ABSTRACT FROM AUTHOR]

The study was aimed to explore the brain imaging characteristics of major depressive disorder (MDD) patients with suicide ideation (SI) through resting-state functional magnetic resonance imaging (rs-fMRI) and to investigate the potential neurobiological role in the occurrence of SI. 50 MDD patients were selected as the experimental group and 50 healthy people as the control group. The brain images of the patients were obtained by MRI. Extraction of EEG biological features was from rs-fMRI images. Since MRI images were disturbed by noise, the initial clustering center of FCM was determined by particle swarm optimization algorithm so that the noise of the collected images was cleared by adaptive median filtering. Then, the image images were processed by the optimized model. The correlation between brain mALFF and clinical characteristics was analyzed. It was found that the segmentation model based on the FCM algorithm could effectively eliminate the noise points in the image; that the zALFF values of the right superior temporal gyrus (R-STG), left middle occipital gyrus (L-MOG), and left middle temporal gyrus (L-MTG) in the observation group were significantly higher than those in the control group (P < 0.05); and that the average zALFF values of left thalamus (L-THA) and left middle frontal gyrus (L-MFG) decreased. The mean zALFF values of L-MFG and L-SFG demonstrated good identification value for SI in MDD patients. In summary, MRI images based on FCM had a good convergence rate, and electrical biological characteristics of brain regions were abnormal in MDD patients with SI, which can be applied to the diagnosis and treatment of patients with depression in clinical practice. [ABSTRACT FROM AUTHOR]

[Display omitted] • Silver coated SMP conductor was fabricated by electroless deposition process. • ON-OFF switching of SMP conductor can be achieved via temperature variation. • The SMP conductor realized fast early fire alarm in fire simulation. • Thermal simulation verified the wide response range of the SMP conductor. Casualties and severe damages of environmental resources resulted from wildfires are to some extent caused by belated evacuating personnel and fighting fires. It is considered that if the timely detection of the high temperature signal can be achieved in the early stage of fire disaster, the duly rescue actions brought by the early fire alarming can extensively avoid casualty accidents and the detrimental fire spread. Therefore, in this work, we fabricate a cross-linked polycaprolactone (PCL) network, and based on its shape memory property and subsequent electroless deposition process, we prepare a smart conductor with ability of switching between non-conductive and conductive at low and high temperatures respectively. Outdoor experiments present that this electrically "OFF-to-ON" conductor can effectively respond to a fire and play a crucial role in early fire alarming under simulated fire scene. The finite element analysis simulation results further prove the advantages of this material over the traditional thermocouple in detecting temperature changes. [ABSTRACT FROM AUTHOR]

Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca2+ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses. Author summary: The outbreaks of emerging infectious diseases have become a severe challenge worldwide, and therefore it is a public health priority to explore novel broad-spectrum antiviral agents with various mechanisms. This study reported that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme during tryptophan metabolism, showed promise as a novel broad-spectrum antiviral factor against emerging pathogenic viruses. We further found that quinolinic acid (QUIN), an enzymatic product of KMO, could also act as a novel broad-spectrum antiviral agent. We then systematically studied the underlying mechanisms and broadly antiviral function of KMO and QUIN in vitro and in vivo. Our data highlight the importance of exploring novel antiviral targets from the key enzymes and their metabolites in tryptophan metabolism. [ABSTRACT FROM AUTHOR]

Fospropofol disodium is a propofol prodrug that is water-soluble and has a reduced risk of bacterial contamination and hypertriglyceridemia compared with propofol. Prior to implementing a large randomized trial, we investigated the feasibility, initial efficacy, and safety of fospropofol disodium compared with propofol in long-term mild-to-moderate sedation in intensive care units (ICUs). Single-centered, prospective, unblind, randomized, parallel-group clinical trial. The general ICU of university-affiliated teaching hospital. Adult patients (n = 60) expected to have mechanical ventilation for >24 h were enrolled and randomly assigned to the fospropofol or propofol group. Interventions: The fospropofol group received continuous fospropofol disodium infusions and the propofol group received continuous propofol infusions. The sedation goal was a score of −3 to 0 on the Richmond Agitation and Sedation Scale (RASS). The primary outcome was the percentage of time spent in the target sedation range without rescue sedation. Safety outcomes were based on adverse events. Blood samples were collected to measure formate concentration in plasma. The median dose was 4.33 (IQR, 3.08–4.94) mg/kg/h in the fospropofol group and 1.96 (IQR, 1.44–2.94) mg/kg/h in the propofol group. The median percentage of time spent in the target RASS range without rescue sedation was identical in both groups, with 83.33% (IQR, 74.43%–100.00%) in the fospropofol group and 83.33% (IQR, 77.45%–100.00%) in the propofol group (p = 0.887). At least one adverse event was identifed in 23 (76.7%) fospropofol patients and 27 (90.0%) propofol patients. The most common adverse events were tachycardia and hypotension. No paresthesia, catheter-related bloodstream infection or propofol infusion syndrome in both groups was reported. Three patients in the fospropofol group had mild hypertriglyceridemia, and nine patients in propofol group had hypertriglyceridemia (mild in eight patients and moderate in one patient) (10% versus 30%, p = 0.104). The formate concentration in plasma was very low, and no significant difference was identified at any time point between the two groups. Fospropofol disodium appears to be a feasible, effective and safe sedative for patients receiving invasive mechanical ventilation with long-term sedation. • Both fospropofol disodium and propofol can provide adequate sedation in ICU patients with mechanical ventilation. • Fospropofol disodium had a comparable safety profile to that of propofol. • The formate concentration in plasma was very low, and no significant difference was identified at any time point between the 2 groups. [ABSTRACT FROM AUTHOR]

• Changes of lipids in meat with preservatives were analyzed by HRMS and lipidomics. • Classes and numbers of lipids in meat with different preservatives were compared. • The 106 significantly changed lipids in 12 classes were quantified. • Less PE 18:1/18:1 content was shown graphically with higher preservatives content. • Preferable preservative nisin with less effect on meat lipids was confirmed. Nisin and potassium sorbate as preservatives are used in a broad range of meat. A lipidomic evaluation was performed on Tan sheep meat treated by two types of preservatives. The addition of potassium sorbate resulted in higher lipid losses compared with nisin treatment. Furthermore, 106 significant lipids of 12 lipid classes (PC, PS, LPS, LPC, PE, PI, LPE, TG, Cer, DG, SM, Sph) with variable importance in projection scores greater than 1.0 were detected and qualified to distinguish different preservatives added meat using UHPLC-Q-Orbitrap MS/MS. LOD and LOQ were 0.12–0.32 μg kg−1 and 0.35–0.89 μg kg−1, indicating high sensitivity and excellent analytical characteristics in the study. Nisin was confirmed to be the better preservative for prolonging the shelf life of Tan sheep meat while reducing the loss of nutrients. These results could provide a strong cornerstone for future research on preservatives in meat products. [ABSTRACT FROM AUTHOR]