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Summary: Macrophage (MΦ) activation and promotion of fibrosis are critical processes in lens capsule healing after injury. Here, we detail a protocol that induces MΦ2 formation within the vitreous body of the eye. Our procedure combines the use of an intravitreal injection of a growth factor (CSF-1) and immunofluorescence to confirm the presence of MΦ2 and fibrotic tissue formation. This protocol allows assessment of the distribution of macrophages and quantification of fibrotic tissue formation/sealing within the vitreous body of mouse eyes.For complete details on the use and execution of this profile, please refer to Li et al. (2021), Gerhardt et al. (2003), Kubota et al. (2009).

Abstract Background Excess cadmium (Cd) intake poses a general risk to health and to the kidneys in particular. Among indices of renal dysfunction under Cd burden measures are the urinary N-acetyl-β-D-glucosidase (UNAG) and urinary β2-microglobulin (Uβ2-MG) enzymes. However, the end-pointed values and the Cd burden threshold remain controversial because the scopes fluctuate widely. Methods To ascertain the clinical benchmark dose of urinary Cd (UCd) burden for renal dysfunction, 1595 residents near a Cd site were surveyed. Urine was sampled and assayed. A benchmark dose low (BMDL) was obtained by fitting UCd levels and index levels. Results We found that over 50% of the subjects were suffering from Cd exposure as their UCd levels far exceeded the national standard threshold of 5.000 μg/g creatinine (cr). Further analysis indicated that Uβ2-MG was more sensitive than UNAG for renal dysfunction. The BMDL for UCd was estimated as 3.486 U/g cr (male, where U is unit of enzyme) and 2.998 U/g cr (female) for UNAG. The BMDL for Uβ2-MG, which is released into urine from glomerulus after Cd exposure, was found to be 2.506 μg/g cr (male, where μg is the unit of microglobulin) and 2.236 μg/g cr (female). Conclusions Uβ2-MG is recommended as the sensitivity index for renal dysfunction, with 2.2 μg/g cr as the threshold for clinical diagnosis. Our findings suggest that Uβ2-MG is the better biomarker for exposure to Cd.

Abstract Background The effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early and late start of norepinephrine support on clinical outcomes in patients with septic shock. Methods We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of March 2020. We included studies involving adult patients (> 18 years) with septic shock. All authors reported our primary outcome of short-term mortality and clearly comparing early versus late norepinephrine initiation with clinically relevant secondary outcomes (ICU length of stay, time to achieved target mean arterial pressure (≥ 65 mmHg), and volume of intravenous fluids within 6 h). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). Results Five studies including 929 patients were included. The primary outcome of this meta-analysis showed that the short-term mortality of the early group was lower than that of the late group (odds ratio [OR] = 0.45; 95% CI, 0.34 to 0.61; P

Abstract Background Heading time is one of the most important agronomic traits in wheat, as it largely affects both adaptation to different agro-ecological conditions and yield potential. Identification of genes underlying the regulation of wheat heading and the development of diagnostic markers could facilitate our understanding of genetic control of this process. Results In this study, we developed 400 recombinant inbred lines (RILs) by crossing a γ-ray-induced early heading mutant (eh1) with the late heading cultivar, Lunxuan987. Bulked Segregant Analysis (BSA) of both RNA and DNA pools consisting of various RILs detected a quantitative trait loci (QTL) for heading date located on chromosomes 5B, and further genetic linkage analysis limited the QTL to a 3.31 cM region. We then identified a large deletion in the first intron of the vernalization gene VRN-B1 in eh1, and showed it was associated with the heading phenotype in the RIL population. However, it is not the mutation loci that resulted in early heading phonotype in the mutant compared to that of wildtype. RNA-seq analysis suggested that Vrn-B3 and several newly discovered genes, including beta-amylase 1 (BMY1) and anther-specific protein (RTS), were highly expressed in both the mutant and early heading pool with the dominant Vrn-B1 genotype compared to that of Lunxuan987 and late heading pool. Enrichment analysis of differentially expressed genes (DEGs) identified several key pathways previously reported to be associated with flowering, including fatty acid elongation, starch and sucrose metabolism, and flavonoid biosynthesis. Conclusion The development of new markers for Vrn-B1 in this study supplies an alternative solution for marker-assisted breeding to optimize heading time in wheat and the DEGs analysis provides basic information for VRN-B1 regulation study.

Abstract Background Patients with lymph node (LN)-positive pancreatic ductal adenocarcinoma (PDAC) have extremely poor survival rates. Circular RNAs (circRNAs), a newly discovered type of endogenous noncoding RNAs, have been proposed to mediate the progression of diverse types of tumors. However, the role and underlying regulatory mechanisms of circRNAs in the LN metastasis of PDAC remain unknown. Methods Next-generation sequencing was used to identify differentially expressed circRNAs between PDAC and normal adjacent tissues. In vitro and in vivo experiments were conducted to evaluate the functional role of circNFIB1. RNA pulldown and luciferase assays were performed to examine the binding of circNFIB1 and miR-486-5p. Results In the present study, we identified that a novel circRNA (circNFIB1, hsa_circ_0086375) was downregulated in PDAC and negatively associated with LN metastasis in PDAC patients. Functionally, circNFIB1 knockdown promoted lymphangiogenesis and LN metastasis of PDAC both in vitro and in vivo. Mechanistically, circNFIB1 functioned as a sponge of miR-486-5p, and partially reversed the effect of miR-486-5p. Moreover, circNFIB1 attenuated the oncogenic effect of miR-486-5p and consequently upregulated PIK3R1 expression, which further downregulated VEGF-C expression through inhibition of the PI3K/Akt pathway, and ultimately suppressed lymphangiogenesis and LN metastasis in PDAC. Conclusions Our findings provide novel insight into the underlying mechanism of circRNA-mediated LN metastasis of PDAC and suggest that circNFIB1 may serve as a potential therapeutic target for LN metastasis in PDAC. Graphical abstract

Abstract Background The activation of NF-κB signaling pathway is regarded as the dominant process that correlates with tumorigenesis. Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play crucial roles in sustaining the NF-κB signaling pathway. However, the underlying mechanisms have not yet been elucidated. Methods The expression and clinical features of PLACT1 were analyzed in a 166-case cohort of PDAC by qRT-PCR and in situ hybridization. The functional role of PLACT1 was evaluated by both in vitro and in vivo experiments. Chromatin isolation by RNA purification assays were utilized to examine the interaction of PLACT1 with IκBα promoter. Results We identified a novel lncRNA-PLACT1, which was significantly upregulated in tumor tissues and correlated with progression and poor survival in PDAC patients. Moreover, PLACT1 promoted the proliferation and invasion of PDAC cells in vitro. Consistently, PLACT1 overexpression fostered the progression of PDAC both in orthotopic and lung metastasis mice models. Mechanistically, PLACT1 suppressed IκBα expression by recruiting hnRNPA1 to IκBα promoter, which led to increased H3K27me3 that decreased the transcriptional level of IκBα. Furthermore, E2F1-mediated overexpression of PLACT1 modulated the progression of PDAC by sustained activation of NF-κB signaling pathway through forming a positive feedback loop with IκBα. Importantly, administration of the NF-κB signaling pathway inhibitor significantly suppressed PLACT1-induced sustained activation of NF-κB signaling pathway, leading to reduced tumorigenesis in vivo. Conclusions Our findings suggest that PLACT1 provides a novel epigenetic mechanism involved in constitutive activation of NF-κB signaling pathway and may represent a new therapeutic target of PDAC.

Abstract Background The effect of alternative spontaneous breathing trial (SBT) techniques on extubation success and other clinically important outcomes is uncertain. A systematic review and meta-analysis was performed to clarify the preferable SBT (T-piece or pressure support ventilation [PSV]). Methods We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) from inception to the 31st of July 2019. We included RCTs involving adult patients (> 18 years) who underwent at least two different SBT methods. All authors reported our primary outcome of successful extubation rate and clearly compared PS versus T-piece with clinically relevant secondary outcomes (rate of reintubation, ICU and hospital length of stay, and ICU and hospital mortality). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). Results Ten RCTs including 3165 patients were included. The results of this meta-analysis showed that there was no significant difference in the successful extubation rate between the T-piece group and PS group (odds ratio [OR] = 0.91; 95% CI, 0.78–1.07; P = 0.27; I 2 = 79%). In addition, compared with the PS group, the T-piece group showed no significant difference in the rate of reintubation (odds ratio [OR] = 0.99; 95% CI, 0.78–1.26; P = 0.95; I 2 = 5%), ICU mortality (odds ratio [OR] = 1.22; 95% CI, 0.83–1.80; P = 0.30; I 2 = 0%), hospital mortality (odds ratio [OR] = 1.36; 95% CI, 0.99–1.87; P = 0.06; I 2 = 19%), ICU length of stay (mean difference = − 0.10; 95% CI, − 0.59 to 0.39; P = 0.69; I 2 = 13%), and hospital length of stay (mean difference = − 0.82;95% CI, − 2.2 to 0.55; P = 0.24; I 2 = 0%). Conclusions T-piece and PSV as SBTs are considered to have comparable predictive power of successful extubation in critically ill patients. The analysis of secondary outcomes also shows no significant difference in the rate of reintubation, ICU and hospital length of stay, and ICU and hospital mortality between the two groups. Further randomized controlled studies of SBTs are still required.

Deployed in a harsh or hostile environment and running in an unattended state, wireless sensor networks (WSNs) are vulnerable to many attacks. The selective forwarding attack is one most difficult to be detected, and trust-based detection methods often fail especially under the poor wireless channels. Based on nodes' cumulative forwarding rates (CFRs) and cumulative transmission rates (CTRs), we propose a clustering scheme in clustered WSNs to divide the nodes into three types: malicious, suspicious, and regular nodes. To defend selective forwarding attacks of malicious nodes, our scheme isolates them from the network. For suspicious nodes, our scheme uses the non-cooperative game with incomplete information to force them to promote forwarding rates. In the game, the reward and punishment mechanism reduces the attackers' expected revenues and trust values. And the suspicious nodes, screened out by our clustering method, will be forced to forward packets to elude our detecting scheme. The Nash equilibrium of the game between regular nodes and suspicious nodes is proved to exist here. Simulation results show that our scheme can promote network throughput largely, and our dynamic-time behavior monitoring scheme can gain a longer network lifetime than that of the full-time behavior monitoring scheme.

In modern manufacturing systems, various industrial communication systems (e.g., fieldbus systems and industrial Ethernet networks) have been used to realize reliable information exchange. However, these industrial communication solutions are largely incompatible with each other, which do not satisfy the new requirements of Industry 4.0. Recently Time-Sensitive Networking (TSN) has been developed to improve the real-time capabilities to the standard Ethernet, and is considered to be a promising real-time communication solution for Industry 4.0. In this work, we propose a communication architecture for a manufacturing system using the Open Platform Communications Unified Architecture (OPC UA) and TSN technologies. TSN is adopted as the communication backbone to connect heterogeneous industrial automation subsystems. The OPC UA is adopted to realize horizontal and vertical communication between subsystems in the field layer and the entities of the upper layers. We implement a laboratory-level manufacturing system to validate the proposed architecture. The experimental results demonstrate the feasibility and capability of the proposed architecture. Moreover, we evaluate the performance of a key TSN substandard, i.e., IEEE 802.1Qbv, in the laboratory-level manufacturing system. The evaluation results demonstrate that IEEE 802.1Qbv can indeed provide excellent real-time capabilities for industrial applications.

Hypoxia inducible factors (HIFs) and their regulatory hydroxylases the prolyl hydroxylase domain enzymes (PHDs) are the key mediators of the cellular response to hypoxia. HIFs are normally hydroxylated by PHDs and degraded, while under hypoxia, PHDs are suppressed, allowing HIF-α to accumulate and transactivate multiple target genes, including erythropoiesis, and genes participate in angiogenesis, iron metabolism, glycolysis, glucose transport, cell proliferation, survival, and so on. Aiming at stimulating HIFs, a group of small molecules antagonizing HIF-PHDs have been developed. Of these HIF-PHDs inhibitors (HIF-PHIs), roxadustat (FG-4592), daprodustat (GSK-1278863), vadadustat (AKB-6548), molidustat (BAY 85-3934) and enarodustat (JTZ-951) are approved for clinical usage or have progressed into clinical trials for chronic kidney disease (CKD) anemia treatment, based on their activation effect on erythropoiesis and iron metabolism. Since HIFs are involved in many physiological and pathological conditions, efforts have been made to extend the potential usage of HIF-PHIs beyond anemia. This paper reviewed the progress of preclinical and clinical research on clinically available HIF-PHIs in pathological conditions other than CKD anemia.

Abstract Background Previous studies have explored the association between parenting style and offspring’s psychological well-being, and the association between offspring’s achievement attribution pattern and psychological well-being. However, little is known about the role of offspring’s achievement attribution in the relationship between parenting and offspring’s psychological well-being. We aimed to find the role of adolescents’ achievement attribution pattern in the relationship between parent–child communication quality and adolescents’ mental health. Methods A cross-sectional analysis was conducted on 2,725 adolescents aged from 9 to 18 years who are participating in the China Family Panel Studies. Participants supplied demographic information and completed a series of psychological scales including the Center for Epidemiologic Studies Depression scale, an adapted version of the Parental Bonding Instrument, an achievement attribution scale, and single-item measures of subjective well-being and subjective interpersonal popularity. Results Linear regression analysis revealed that after controlling for demographic factors good parent–child communication negatively correlated with depression symptoms, and positively associated with subjective well-being and subjective interpersonal popularity. Next, mediation analysis found that internal attribution of achievement partly mediated the effects of parent–child communication quality on adolescents’ depression, subjective well-being, and subjective interpersonal popularity. The result was robust after controlling demographic variables. Conclusions An internal attribution pattern of achievement partially accounted for the associations between parent–child communication quality and adolescents’ psychological outcomes including depression, subjective well-being, and subjective interpersonal popularity. Future interventions for adolescents’ mental health promotion can target parent–child communication and adolescents’ positive achievement attribution pattern.

Based on the advection-diffusion equation of suspended sediment, a general formula of vertical distribution of suspended sediment concentration was derived by considering the influence of vertical velocity. The new formula was tested against over 3000 sets of field data and obtained a reasonable agreement. Comparing with the Rouse equation of concentration, the accuracy of the new formula increases significantly, and the shortcoming of the underestimation of the Rouse profile in practical application is revised. Through the analysis of the new formula with different vertical time-averaged velocity coefficients m, it was found that vertical velocity does have an impact on the accurate estimation of sediment concentration, and the extent of which is related to the value of sediment concentration. Utilizing the regression analysis, it was found the vertical time-averaged velocity coefficient m increases with the height above the bed.

In order to improve the visual communication effect of the 3D image visual communication system, this article combines the automatic reconstruction technology of digital images to design the 3D image visual communication system. Moreover, this article studies the shock stability of the shock capture scheme by combining entropy generation analysis, linear disturbance analysis, and numerical experiments. In addition to this, this article presents a general method that can be used to suppress numerical shock instabilities in various Godunov-type schemes. It can be seen from the experimental results that the proposed 3D image visual communication system for the automatic reconstruction of digital images has a good visual communication effect.

BackgroundImmune checkpoint inhibitor (ICI) therapy dramatically prolongs melanoma survival. Currently, the identified ICI markers are sometimes ineffective. The objective of this study was to identify novel determinants of ICI efficacy.MethodsWe comprehensively curated pretreatment somatic mutational profiles and clinical information from 631 melanoma patients who received blockade therapy of immune checkpoints (i.e., CTLA-4, PD-1/PD-L1, or a combination). Significantly mutated genes (SMGs), mutational signatures, and potential molecular subtypes were determined. Their association with ICI responses was assessed simultaneously.ResultsWe identified 27 SMGs, including four novel SMGs (COL3A1, NRAS, NARS2, and DCC) that are associated with ICI efficacy and well-known driver genes. COL3A1 mutations were associated with improved ICI overall survival (hazard ratio (HR): 0.64, 95% CI: 0.45–0.91, p = 0.012), whereas immune resistance was observed in patients with NRAS mutations (HR: 1.42, 95% CI: 1.10–1.82, p = 0.006). The presence of the tobacco smoking-related signature was significantly correlated with inferior prognoses (HR: 1.42, 95% CI: 1.11–1.82, p = 0.005). In addition, the signature resembling that of alkylating agents and a newly discovered signature both exhibited extended prognoses (both HR

The wheat AP2 family gene Q controls domestication traits, including spike morphology and threshability, which are critical for the widespread cultivation and yield improvement of wheat. Although many studies have investigated the molecular mechanisms of the Q gene, its direct target genes, especially those controlling spike morphology, are not clear, and its regulatory pathways are not well established. In this study, we conducted gene mapping of a wheat speltoid spike mutant and found that a new allele of the Q gene with protein truncation played a role in spike morphology variation in the mutant. Dynamic expression levels of the Q gene throughout the spike development process suggested that the transcript abundances of the mutant were decreased at the W6 and W7 scales compared to those of the WT. We identified several mutation sites on the Q gene and showed that mutations in different domains resulted in distinct phenotypes. In addition, we found that the Q gene produced three transcripts via alternative splicing and that they exhibited differential expression patterns in nodes, internodes, flag leaves, and spikes. Finally, we identified several target genes directly downstream of Q, including TaGRF1-2D and TaMGD-6B, and proposed a possible regulatory network. This study uncovered the target genes of Q, and the results can help to clarify the mechanism of wheat spike morphology and thereby improve wheat grain yield.

Induced mutagenesis is a powerful approach for the creation of novel germplasm and the improvement of agronomic traits. The evaluation of mutagenic effects and functional variations in crops is needed for breeding mutant strains. To investigate the mutagenic effects of gamma-ray irradiation in wheat, this study characterized genomic variations of wheat early heading mutant (eh1) as compared to wild-type (WT) Zhongyuan 9 (ZY9). Whole-genome resequencing of eh1 and ZY9 produced 737.7 Gb sequencing data and identified a total of 23,537,117 homozygous single nucleotide polymorphism (SNP) and 1,608,468 Indel. Analysis of SNP distribution across the chromosome suggests that mutation hotspots existed in certain chromosomal regions. Among the three subgenomes, the variation frequency in subgenome D was significantly lower than in subgenomes A and B. A total of 27.8 Gb data were obtained by exome-capturing sequencing, while 217,948 SNP and 13,554 Indel were identified. Variation annotation in the gene-coding sequences demonstrated that 5.0% of the SNP and 5.3% of the Indel were functionally important. Characterization of exomic variations in 12 additional gamma-ray-induced mutant lines further provided additional insights into the mutagenic effects of this approach. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis suggested that genes with functional variations were enriched in several metabolic pathways, including plant–pathogen interactions and ADP binding. Kompetitive allele-specific PCR (KASP) genotyping with selected SNP within functional genes indicated that 85.7% of the SNPs were polymorphic between the eh1 and wild type. This study provides a basic understanding of the mechanism behind gamma-ray irradiation in hexaploid wheat.

Distributed self-organization and self-management is an ideal way to achieve an autonomous and efficient operation of large-scale remote sensing satellite swarm. A distributed task allocation method based on the improved contract network algorithm is designed, orienting typical mission-level tasks. And the satellite swarm task allocation and planning model of potential target searching, moving target tracking, and sensitive target feature confirmation is given. The model is composed of observation requirement generation, observing area decomposition, and task allocation between different satellites. Simulation results confirm that the improved contract network algorithm can optimally solve the problem of mission-level task allocation autonomously in distributed swarm. This paper verifies that the self-organization method has the potential for engineering applications with simple realization theory and high calculation efficiency.

In this study, the diversity of putative mycoviruses present in 66 strains of binucleate Rhizoctonia (BNR, including anastomosis group (AG)-A, AG-Fa, AG-K, and AG-W) and 192 strains of multinucleate Rhizoctonia (MNR, including AG-1-IA, AG-2-1, AG-3 PT, AG-4HGI, AG-4HGII, AG-4HGIII, and AG-5), which are the causal agents of potato stem canker or black scurf, was studied using metatranscriptome sequencing. The number of contigs related to mycoviruses identified from BNR and MNR was 173 and 485, respectively. On average, each strain of BNR accommodated 2.62 putative mycoviruses, while each strain of MNR accommodated 2.53 putative mycoviruses. Putative mycoviruses detected in both BNR and MNR contained positive single-stranded RNA (+ssRNA), double-stranded RNA (dsRNA), and negative single-stranded RNA (-ssRNA) genomes, with +ssRNA genome being the prevalent nucleic acid type (82.08% in BNR and 75.46% in MNR). Except for 3 unclassified, 170 putative mycoviruses found in BNR belonged to 13 families; excluding 33 unclassified, 452 putative mycoviruses found in MNR belonged to 19 families. Through genome organization, multiple alignments, and phylogenetic analyses, 4 new parititviruses, 39 novel mitoviruses, and 4 new hypoviruses with nearly whole genome were detected in the 258 strains of BNR and MNR.

Malignant tumor is one of the leading causes of death in human beings. In recent years, bacteriophages (phages), a natural bacterial virus, have been genetically engineered for use as a probe for the detection of antigens that are highly expressed in tumor cells and as an anti-tumor reagent. Furthermore, phages can also be chemically modified and assembled with a variety of nanoparticles to form a new organic/inorganic composite, thus extending the application of phages in biological detection and tumor therapeutic. This review summarizes the studies on genetically engineered and chemically modified phages in the diagnosis and targeting therapy of tumors in recent years. We discuss the advantages and limitations of modified phages in practical applications and propose suitable application scenarios based on these modified phages.

The highly conserved and dynamically reversible N6-methyladenine (m6A) modification has emerged as a critical gene expression regulator by affecting RNA splicing, translation efficiency, and stability at the post-transcriptional level, which has been established to be involved in various physiological and pathological processes, including glycolipid metabolism and the development of glycolipid metabolic disease (GLMD). Hence, accumulating studies have focused on the effects and regulatory mechanisms of m6A modification on glucose metabolism, lipid metabolism, and GLMD. This review summarizes the underlying mechanism of how m6A modification regulates glucose and lipid metabolism-related enzymes, transcription factors, and signaling pathways and the advances of m6A regulatory mechanisms in GLMD in order to deepen the understanding of the association of m6A modification with glycolipid metabolism and GLMD.

Ticks and tick-borne pathogens pose a significant threat to the health and welfare of humans and animals. Our knowledge about pathogens carried by ticks of Australian wildlife is limited. This study aimed to characterise ticks and tick-borne microorganisms from a range of wildlife species across six sites in Victoria, Australia. Following morphological and molecular characterisation (targeting 16S rRNA and cytochrome c oxidase I), tick DNA extracts (n = 140) were subjected to microfluidic real-time PCR-based screening for the detection of microorganisms and Rickettsia-specific real-time qPCRs. Five species of ixodid ticks were identified, including Aponomma auruginans, Ixodes (I.) antechini, I. kohlsi, I. tasmani and I. trichosuri. Phylogenetic analyses of 16S rRNA sequences of I. tasmani revealed two subclades, indicating a potential cryptic species. The microfluidic real-time PCR detected seven different microorganisms as a single (in 13/45 ticks) or multiple infections (27/45). The most common microorganisms detected were Apicomplexa (84.4%, 38/45) followed by Rickettsia sp. (55.6%, 25/45), Theileria sp. (22.2% 10/45), Bartonella sp. (17.8%, 8/45), Coxiella-like sp. (6.7%, 3/45), Hepatozoon sp. (2.2%, 1/45), and Ehrlichia sp. (2.2%, 1/45). Phylogenetic analyses of four Rickettsia loci showed that the Rickettsia isolates detected herein potentially belonged to a novel species of Rickettsia. This study demonstrated that ticks of Australian wildlife carry a diverse array of microorganisms. Given the direct and indirect human–wildlife–livestock interactions, there is a need to adopt a One Health approach for continuous surveillance of tick-associated pathogens/microorganisms to minimise the associated threats to animal and human health.

Zika virus (ZIKV) is an RNA-enveloped virus that belongs to the Flavivirus genus, and ZIKV infections potentially induce severe neurodegenerative diseases and impair male fertility. Palmitoylation is an important post-translational modification of proteins that is mediated by a series of DHHC-palmitoyl transferases, which are implicated in various biological processes and viral infections. However, it remains to be investigated whether palmitoylation regulates ZIKV infections. In this study, we initially observed that the inhibition of palmitoylation by 2-bromopalmitate (2-BP) enhanced ZIKV infections, and determined that the envelope protein of ZIKV is palmitoylated at Cys308. ZDHHC11 was identified as the predominant enzyme that interacts with the ZIKV envelope protein and catalyzes its palmitoylation. Notably, ZDHHC11 suppressed ZIKV infections in an enzymatic activity-dependent manner and ZDHHC11 knockdown promoted ZIKV infection. In conclusion, we proposed that the envelope protein of ZIKV undergoes a novel post-translational modification and identified a distinct mechanism in which ZDHHC11 suppresses ZIKV infections via palmitoylation of the ZIKV envelope protein.

Liver fibrosis is a progressive liver damage condition caused by various factors and may progress toward liver cirrhosis, and even hepatocellular carcinoma. Many studies have found that the disfunction in metabolism could contribute to the development of liver fibrosis. Geniposide, derived from Gardenia jasminoides J. Ellis, has been demonstrated with therapeutic effects on liver fibrosis. However, the exact molecular mechanisms of such liver-protection remain largely unknown. The aim of this study was to explored the effect of geniposide on metabolic regulations in liver fibrosis. We used carbon tetrachloride (CCl4) to construct a mouse model of liver fibrosis and subsequently administered geniposide treatment. Therapeutic effects of geniposide on liver fibrosis were accessed through measuring the levels of hepatic enzymes in serum and the pathological changes in liver. We also investigated the effects of geniposide on inflammatory response, oxidative stress and apoptosis in liver. Furthermore, serum untargeted metabolomics were used to explore the metabolic regulatory mechanisms behind geniposide on liver fibrosis. Our results demonstrated that geniposide could reduce the levels of hepatic enzymes in serum and ameliorate the pathological changes in liver fibrosis mice. Geniposide enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased methane dicarboxylic aldehyde (MDA) levels in liver. Geniposide treatment also decreased the levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-a) in liver tissue homogenate. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining demonstrated that geniposide could reduce the apoptosis of hepatocytes. Geniposide increased the protein expression of B-cell lymphoma-2 (Bcl-2) and downregulated the protein expression of Bcl-2 Associated X (Bax), cleaved-Caspase 3, and cleaved-Caspase 9. Serum untargeted metabolomics analysis demonstrated that geniposide treatment improved the metabolic disorders including glycerophospholipid metabolism, arginine and proline metabolism, and arachidonic acid (AA) metabolism. In conclusion, our study demonstrated the protective effects of geniposide on liver fibrosis. We found that geniposide could treat liver fibrosis by inhibiting oxidative stress, reducing inflammatory response and apoptosis in the liver, and modulating glycerophospholipid, and arginine, proline, and AA metabolism processes.

Background: Parkinson’s disease (PD) is a neurodegenerative movement disease that includes non-motor symptoms such as cognitive impairment. Long-term mind-body exercise has been shown to improve cognitive ability in PD patients, but the methods of assessment and intervention were inconsistent across studies. Wuqinxi is a mind-body exercise that is easy to learn, has few physical and cognitive demands, and is recommended for PD patients. Dynamic functional connectivity (DFC) has been associated with cognitive alterations in PD patients, but no studies have yet explored the effects of Wuqinxi on this association. The current protocol is designed to measure the effects of long-term Wuqinxi intervention on cognition in PD patients, and explore the underlying neural mechanisms through DFC.Methods: A long-term single-blind, randomized trial will be conducted. PD patients and age- and gender-matched HC will be recruited; PD patients will be randomly assigned to either Wuqinxi or balance groups, and HC will all receive health education. The Wuqinxi group will receive a 90-min session of Wuqinxi intervention three times a week for 24 weeks, while the balance group will receive balance exercise instruction on the same schedule. Primary outcomes will include assessment of cognitive domains and dynamic temporal characteristics of functional connectivity. Secondary outcomes will include severity of motor symptoms, mobility, balance, and emotional state. Assessments will be conducted at baseline, at the end of 24 weeks of intervention, and 12 weeks after interventions have ended.Discussion: This study will provide evidence to the effects of Wuqinxi exercise on cognitive improvements in PD patients from the perspective of DFC, and will contribute to the understanding of neural mechanisms underlying cognitive enhancement through Wuqinxi practice.Clinical Trial Registration:www.chictr.org.cn, identifier ChiCTR2000038517.

This study analyzes the impact of Industry 4.0 and SARS-CoV-2 on the manufacturing industry, in which manufacturing entities are faced with insufficient resources and uncertain services; however, the current study does not fit this situation well. A multi-service composition for complex manufacturing tasks in a cloud manufacturing environment is proposed to improve the utilization of manufacturing service resources. Combining execution time, cost, energy consumption, service reliability and availability, a quality of service (QoS) model is constructed as the evaluation standard. A hybrid search algorithm (VS–ABC algorithm) based on the vortex search algorithm (VS) and the artificial bee colony algorithm (ABC) is introduced and combines the advantages of the two algorithms in search range and calculation speed. We take the customization production of automobiles as an example, and the case study shows that the VS–ABC algorithm has better applicability compared with traditional vortex search and artificial bee colony algorithms.

The forming of zinc dross floating on the surface of molten zinc in zinc pot is inevitable during hot-dip galvanizing production. The cleaning of zinc dross has always been a challenge and a difficult problem to solve. Based on the electromagnetic field theory and its application, a new electromagnetic dross removal technology was proposed, and the zinc dross driven by flowing molten zinc was possible to remove in an electromagnetic field circumstance. Through the coupling simulation of electromagnetic field and flow field, the electromagnetic force acting on molten zinc and the flow situation of molten zinc were simulated. The results showed that electromagnetic field can effectively act on the top surface of molten zinc and affect the flow of molten zinc. Different load conditions of electromagnetic field and the distance between the bottom surface of the iron core and the top surface of molten zinc related to zinc dross removal effect were discussed. Finally, the optimal application parameters of the electromagnetic dross removal technology were put forward.

This paper combines the green industrial strategy and green financial policies for the construction industry implemented in China in the context of carbon neutrality. A total of 67 listed companies in the construction industry from 2017 to 2020 were taken as the research sample, the green financing efficiency was measured, and its influencing factors were identified based on the three-stage DEA and systematic GMM method. The findings show that the green financing efficiency of listed companies in the construction industry is not high overall, although it is increasing. There are obvious differences in subsectors, among which, the efficiency of architectural design and service industries is relatively high. Overall, the financial environment, and the interaction between the government and the financial market, significantly and positively influence the green financing efficiency. In addition, the macroeconomic environment and the government–enterprise relationship has a complex impact on the green financing efficiency. The ownership concentration and having corporate executives with a financial background have a significant positive impact on the green financing efficiency, and the enterprise size, the debt maturity structure, and the R&D and innovation capability have a significant negative impact. The findings of this paper have implications for the improvement of the policy system that supports green development in the construction industry, and provide guidance for the strategic adjustment of the construction industry itself.

To reflect the volatile differences of dried citrus peel as affected by cultivars and drying methods, the volatile compounds of dried citrus peel of two cultivars (Citrus reticulata “Chachi” and Citrus reticulata “Ponkan”), prepared under three drying methods (sun-drying (SD), hot-air-drying (AD), and freeze-drying (FD)), were analyzed by GC-MS, odor activity values (OAVs), and GC-IMS. GC-MS data indicated that SD was favorable to preserve terpenic alcohols (linalool, α-terpineol and terpinene-4-ol), β-cymene, methyl methanthranilate, and monoterpenes; while AD was favorable to preserve aliphatic aldehydes and sesquiterpenes; and SD was more similar with AD in GC-MS analysis of volatile profile (of higher MW) for both cultivars from the PCA outcome. Furthermore, significant difference in volatile isomeric composition of different samples was also clearly demonstrated through extracted ion chromatogram (EIC) by GC-MS analysis. GC-IMS analysis showed the favorability of FD to preserve ketones, phenols, esters, and aromatic aldehydes; and SD was more similar with FD in GC-IMS analysis of volatile profile (of smaller MW) for both cultivars from the PCA outcome. Moreover, the OAVs indicate that 2-methoxy-4-vinylphenol contributed much to the flavor of dried Ponkan peel, while 2-methoxy-4-vinylphenol, methyl methanthranilate, and methyl anthranilate played an important role in the flavor of dried Chachi peel; and the highest OAVs for monoterpenes were observed at SD for both cultivars. Thus, the combination of GC-MS and GC-IMS analyses with PCA in this paper suggested the superiority of SD to preserve volatiles and characteristic aroma in dried citrus peel, and that SD contributed much to the quality of dried Chachi peel.

Different crystal planes of nanocrystalline often displayed diverse physical and chemical properties. In this paper, the effects of nano-ZnO with two kinds of crystal planes on crystallization, thermal stability and mechanical properties of PLLA were investigated. The results show that the (1010) planes with no-polar and low surface energy increased the chain mobility of PLLA chain, showed a plasticizing effect; the glass transition temperature, melt and cold crystallization temperature decreased by 12 °C, 10 °C and 12 °C, respectively. The size of spherulites increased and the number of spherulites decreased, the crystal form changed from mixed crystal form α, α′ to unique α crystal form. However, the (0002) planes with polar and high surface energy has highly nucleating effective for PLLA, the crystallization temperature increased to 106.41 °C, the cold crystallization peak disappear. The size of spherulites decreased and the number of spherulites increased. Moreover, the (0002) planes increases the elongation at break of PLLA to 20.34% but the (1010) planes reduces to 7.49%. Their thermo-gravimetric analysis results showed the similar trend. Our results indicate that the interface wettability and compatibility between crystal planes and PLLA, which was caused by the polarity and surface energy of (1010) or (0002) planes played key role in improving the performance of polymers.

Hepatocellular carcinoma (HCC) remains a devastating malignancy worldwide due to lack of effective therapy. The immune-rich contexture of HCC tumor microenvironment (TME) makes this tumor an appealing target for immune-based therapies; however, the immunosuppressive TME is still a major challenge for more efficient immunotherapy in HCC. Using bioinformatics analysis based on the TCGA database, here we found that MAPK10 is frequently down-regulated in HCC tumors and significantly correlates with poor survival of HCC patients. HCC patients with low MAPK10 expression have lower expression scores of tumor infiltration lymphocytes (TILs) and stromal cells in the TME and increased scores of tumor cells than those with high MAPK10 expression. Further transcriptomic analyses revealed that the immune activity in the TME of HCC was markedly reduced in the low-MAPK10 group of HCC patients compared to the high-MAPK10 group. Additionally, we identified 495 differentially expressed immune-associated genes (DIGs), with 482 genes down-regulated and 13 genes up-regulated in parallel with the decrease of MAPK10 expression. GO enrichment and KEGG pathway analyses indicated that the biological functions of these DIGs included cell chemotaxis, leukocyte migration and positive regulation of the response to cytokine–cytokine receptor interaction, T cell receptor activation and MAPK signaling pathway. Protein–protein interaction (PPI) analyses of the 495 DIGs revealed five potential downstream hub genes of MAPK10, including SYK, CBL, VAV1, LCK, and CD3G. Several hub genes such as SYK, LCK, and VAV1 could respond to the immunological costimulatory signaling mediated by the transmembrane protein ICAM1, which was identified as a down-regulated DIG associated with low-MAPK10 expression. Moreover, ectopic overexpression or knock-down of MAPK10 could up-regulate or down-regulate ICAM1 expression via phosphorylation of c-jun at Ser63 in HCC cell lines, respectively. Collectively, our results demonstrated that MAPK10 down-regulation likely contributes to the immunosuppressive TME of HCC, and this gene might serve as a potential immunotherapeutic target and a prognostic factor for HCC patients.

A novel polysaccharide (CMP-2B) was purified from Centipeda minima by anion-exchange and gel-permeation chromatography. Structural characterization revealed that CMP-2B was a homogeneous heteropolysaccharide with an average molecular weight of 113.193 KDa. CMP-2B was made up of mannose, galacturonic acid, galactose and arabinose with a molar ratio of 0.27:0.12:0.42:0.17. The backbone chain of CMP-2B consisted of 3,6)-α-D-Manp-(1 and 4,6)-β-D-Galp-(1, and the branches were comprised of 4)-α-D-GalpA-(1, 6)-β-D-Galp-(1, T-α-L-Araf-(1 and 3)-α-L-Araf -(1. Besides, the results of antioxidant assays revealed that CMP-2B possessed signifcant free radical scavenging ability. Moreover, the results of hypoglycemic assays showed that CMP-2B displayed α-glucosidase inhibitory activities, and could significantly improve glucose consumption, glycogen synthesis and the activity of pyruvate kinase of insulin-resistance HepG2 cells. Overall, these results suggested that CMP-2B could be a new source for functional foods.

Recently, several reports have suggested that the growth and grain yield of wheat are significantly influenced by high atmospheric carbon dioxide concentration (CO2) because of it photosynthesis enhancing effects. Moreover, it has been proposed that plants with large carbon sink size will benefit more from CO2 enrichment than those with small carbon sink size. However, this hypothesis is yet to be test in winter wheat plant. Therefore, the aim of this study was to examine the effect of elevated CO2 (eCO2) conditions on the quantum efficiency of photosystem II (PSII) photochemistry in large ear-type (cv. Shanhan 8675; greater ear C sink strength) and small multiple ear-type (cv. Early premium; greater vegetative C source strength) winter wheat varieties. The experiment was conducted in a free air CO2 enrichment (FACE) facility, and three de-excitation pathways of the primary reaction of PSII of flag leaf at the anthesis stage were evaluated under two CO2 concentrations (ambient [CO2], ∼415 μmol⋅mol–1, elevated [CO2], ∼550 μmol⋅mol–1) using a non-destructive technique of modulated chlorophyll fluorescence. Additionally, the grain yield of the two varieties was determined at maturity. Although elevated CO2 increased the quantum efficiency of PSII photochemistry (ΦPSII) of Shanhan 8675 (SH8675) flag leaves at the anthesis stage, the grain number per ear and 1,000-kernel weight were not significantly affected. In contrast, the ΦPSII of early premium (ZYM) flag leaves was significantly lower than that of SH8675 flag leaves at the anthesis stage, which was caused by an increase in the regulatory non-photochemical energy dissipation quantum (ΦNPQ) of PSII, suggesting that light energy absorbed by PSII in ZYM flag leaf was largely dissipated as thermal energy. The findings of our study showed that although SH8675 flag leaves exhibited higher C sink strength and quantum efficiency of PSII photochemistry at the anthesis stage, these factors alone do not ensure improved grain yield under eCO2 conditions.

Abstract Background Patients with lymph node (LN) metastatic bladder cancer (BCa) present with extremely poor prognosis. BCa‐derived exosomes function as crucial bioactive cargo carriers to mediate the signal transduction in tumor microenvironment triggering tumor metastasis. However, the mechanisms underlying exosome‐mediated LN metastasis in BCa are unclear. Methods We conducted the high‐throughput sequencing to explore the expression profile of long noncoding RNA (lncRNA) in urinary exosomes (urinary‐EXO) from patients with BCa and further evaluated the clinical relevance of exosomal lncRNA BCYRN1 in a larger 210‐case cohort. The functional role of exosomal BCYRN1 was evaluated through the migration and tube formation assays in vitro and the footpad‐popliteal LN metastasis model in vivo. RNA pull‐down assays, luciferase assays, and actinomycin assays were conducted to detect the regulatory mechanism of exosomal BCYRN1. Results LncRNA BCYRN1 was substantially upregulated in urinary‐EXO from patients with BCa, and associated with the LN metastasis of BCa. We demonstrated that exosomal BCYRN1 markedly promoted tube formation and migration of human lymphatic endothelial cells (HLECs) in vitro and lymphangiogenesis and LN metastasis of BCa in vivo. Mechanistically, BCYRN1 epigenetically upregulated WNT5A expression by inducing hnRNPA1‐associated H3K4 trimethylation in WNT5A promoter, which activated Wnt/β‐catenin signaling to facilitate the secretion of VEGF‐C in BCa. Moreover, exosomal BCYRN1 was transmitted to HLECs to stabilize the VEGFR3 mRNA and thus formed an hnRNPA1/WNT5A/VEGFR3 feedforward regulatory loop, ultimately promoting the lymphatic metastasis of BCa. Importantly, blocking VEGFR3 with specific inhibitor, SAR131675 significantly impaired exosomal BCYRN1‐induced the LN metastasis in vivo. Clinically, exosomal BCYRN1 was positively associated with the shorter survival of BCa patients and identified as a poor prognostic factor of patients. Conclusion Our results uncover a novel mechanism by which exosomal BCYRN1 synergistically enhances VEGF‐C/VEGFR3 signaling‐induced lymphatic metastasis of BCa, indicating that BCYRN1 may serve as an encouraging therapeutic target for patients with BCa.

Summary: Emerging evidence challenges the lens as an immune-privileged organ. Here, we provide a direct mechanism supporting a role of macrophages in lens capsule rupture repair. Posterior lens capsule rupture in a connexin 50 and aquaporin 0 double-knockout mouse model resulted in lens tissue extrusion into the vitreous cavity with formation of a “tail-like” tissue containing delayed regressed hyaloid vessels, fibrotic tissue and macrophages at postnatal (P) 15 days. The macrophages declined after P 30 days with M2 macrophages detected inside the lens. By P 90 days, the “tail-like” tissue completely disappeared and the posterior capsule rupture was sealed with thick fibrotic tissue. Colony-stimulating factor 1 (CSF-1) accelerated capsule repair, whereas inhibition of the CSF-1 receptor delayed the repair. Together, these results suggest that lens posterior rupture leads to the recruitment of macrophages delivered by the regression delayed hyaloid vessels. CSF-1-activated M2 macrophages mediate capsule rupture repair and development of fibrosis.

In this study, mulberry cultivars were found to have abundant bioactive compounds such as phenolics (100.97–586.23 mg gallic acid equivalents/100 g fresh weight), flavonoids (16.38–368.16 mg rutin equivalents/100 g fresh weight) and procyanidins (4.20–121.56 mg catechin equivalents/100 g fresh weight) after in vitro digestion. HPLC-TOF-MS analysis revealed that digested mulberry cultivars contained multiple phenolic compounds including cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside. After gut microbiota fermentation, the contents of anthocyanins were increased initially, then decreased with time, and some anthocyanin metabolites (such as 3,4-Dihydroxybenzoic acid, 2,4,6-trihydroxybenzoic acid, 2,4,6-trihydroxybenzaldehyde, etc.) were detected. Our further cellular study indicated that mulberry (Hanguo) possessed reactive oxygen species scavenging capacity after gut microbiota fermentation. Our results indicated that the new cultivar Hanguo contained abundant polyphenols and exhibited potent antioxidant property after in vitro digestion and gut microbiota fermentation compared with other mulberry cultivars, which could be recommended as a dietary source of functional foods.

Abstract Purpose To assess the worst-case robust optimization IMPT plans with setup and range uncertainties and to test the hypothesis that the worst-case robust optimization strategies could cover most possible setup and range uncertainties in the real scenarios. Methods We analyzed the nominal and worst-case robust optimization IMPT plans of seven patients with head and neck cancer patients. To take uncertainties into account for the dose calculation, we performed a comprehensive simulation in which the dose was recalculated 625 times per given plan using Gaussian systematic setup and proton range uncertainties. Subsequently, based on the simulation results, we calculated the target coverage in all perturbation scenarios, as well as the ratios of target coverage located within the threshold of eight worst-case scenarios. We set the criteria for the optimized plan to be the ratios of 1) the dose delivered to 95% (D95%) of clinical target volumes 1 and 2 (CTV1 and CTV2) above 95% of the prescribed dose, and 2) the D95% of clinical target volume 3 (CTV3) above 90% of the prescribed dose in worst-case situations. Results The probability that the perturbed-dose indices of the CTVs in each scenario were within the worst-case scenario limits ranged from 89.51 to 91.22% for both the nominal and worst-case robust optimization IMPT plans. A quartile analysis showed that the selective robust optimization IMPT plans all had higher D95% values for CTV1, CTV2, and CTV3 than did the nominal IMPT plans. Conclusions The worst-case strategy for robust optimization is adequately models and covers most of the setup and range uncertainties for the IMPT treatment of head and neck patients in our center.

Mulberry has attracted wide attention due to its substantial nutritional values. This work first studied the protective effect of mulberry anthocyanins (MAS) on dextran sulfate sodium (DSS)-induced colitis. The mice experiment was designed as four groups including normal mice (Control), dextran sodium sulfate (DSS)-fed mice, and DSS plus 100 mg/kg·bw MAS-fed mice (LMAS-DSS) or DSS plus 200 mg/kg·bw MAS-fed mice (HMAS-DSS). Mice were given MAS by gavage for 1 week, and then DSS was added to the drinking water for 7 days. MAS was administered for a total of 17 days. The results showed that oral gavage of MAS reduced the disease activity index (DAI), prevented colon shortening, attenuated colon tissue damage and inflammatory response, suppressed colonic oxidative stress and restored the protein expression of intestinal tight junction (TJ) protein (ZO-1, occludin and claudin-3) in mice with DSS-induced colitis. In addition, analysis of 16S rRNA amplicon sequences showed that MAS reduced the DSS-induced intestinal microbiota dysbiosis, including a reduction in Escherichia-Shigella, an increase in Akkermansia, Muribaculaceae and Allobaculum. Collectively, MAS alleviates DSS-induced colitis by maintaining the intestinal barrier, modulating inflammatory cytokines, and improving the microbial community.

Non-keyhole friction stir welding (N-KFSW) is a technique that can fabricate a welding joint without a keyhole through a one-time welding process. The Al–Mg–Si alloy was chosen as a research object, and the N-KFSW technique was investigated by numerical and experimental methods. Firstly, the sleeve bottoms of the N-KFSW welding tool system were innovatively optimized in this study. The optimal sleeve bottom with an 80° angle between the spiral groove and the sleeve inner side wall allowed avoiding the incomplete root penetration defect at the bottom of the stir zone (SZ), which was verified by numerical results and the C-shaped line height. Then, using a 3 mm-thick aluminum alloy as the experimental material, the material flow and joint formation characteristics and mechanical properties at 110, 150 and 190 mm/min welding speeds were studied and compared. The results showed that the SZ presented a drum shape due to the action of the clamping ring and the threads on the side wall of the sleeve. The SZ width decreased from 7.17 to 6.91 mm due to the decreased heat input. From 70 to 210 mm/min welding speed, the maximum tensile strength of the joint was 250 MPa at 190 mm/min, and the joint with relatively higher strength fractured at the heat-affected zone.

Imbalance of gut microbiota can induce or aggravate intestinal inflammation. To enhance our understanding of the molecular mechanisms of gut microbiota and inflammatory bowel disease (IBD), we studied the role of repulsive guidance molecule b (RGMb) in gut microbiota and colitis in mice. We generated Rgmb knockout mice and inducible Rgmb knockout mice and induced colitis using dextran sulfate sodium (DSS) in these mice. 16S ribosomal RNA (rRNA) high-throughput sequencing was performed to acquire the gut microbiota composition and abundance. We found that Rgmb deficiency significantly altered the diversity of gut microbiota and also induced dysbiosis. In sharp contrast to the balanced distribution of various bacteria in control mice, Prevotellaceae was almost exhausted in Rgmb-deficient mice under both basal and inflammatory conditions. Correlation analysis indicated that Prevotellaceae was negatively associated with inflammation in Rgmb-deficient mice with colitis. Similar results were obtained at the early inflammatory stage of colitis associated colon cancer (CAC). Taken together, our results reveal that Rgmb deficiency leads to dysbiosis of predominant gut microbiota under basal and inflammatory conditions. Rgmb-deficiency-mediated Prevotellaceae loss may render mice more susceptible to intestinal inflammation. Therefore, RGMb may be a novel potential target for reconstruction of the gut microbiota for the treatment of IBD.

This study aims to investigate whether simple and convenient progressive relaxation training (PRT) is effective in enhancing collegiate student athletes’ mental health and sports performance. An experimental group of 14 (6 female) and a control group of 10 (5 female) collegiate student athletes were recruited from among track and field athletes who were preparing for provincial competition. The experimental group was exposed to a PRT intervention in 30-min sessions conducted twice per week for a duration of one month. At baseline, the Competitive State Anxiety Inventory-2 (CSAI-2), State-Trait Anxiety Inventory (STAI), and Eysenck Personality Questionnaire-Revised Short Scale for Chinese (EPQ-RSC) were completed, while only the CSAI-2 was reassessed at one, two, and three weeks after initiation of the intervention. Additionally, within half a day after completing all one’s individual competition events, the CSAI-2 was again assessed in the two groups recalling their memory of their precompetition state anxiety. Then, the differences in the three dimensions of the CSAI-2 between the two groups at the five time points introduced above were compared. This study also explored whether PRT affected sports performance, defined by the athletes reaching their best records or not, by logistic regressive analysis. This study found significant between-group differences in the self-confidence dimension score at the second and third time points. Through logistic regression analysis, a positive effect of PRT was found for the enhancement of sports performance. In sum, PRT showed positive effects on precompetition state self-confidence and enhanced sports performance among collegiate student athletes.

Agronomic traits such as heading date (HD), plant height (PH), thousand grain weight (TGW), and spike length (SL) are important factors affecting wheat yield. In this study, we constructed a high-density genetic linkage map using the Wheat55K SNP Array to map quantitative trait loci (QTLs) for these traits in 207 recombinant inbred lines (RILs). A total of 37 QTLs were identified, including 9 QTLs for HD, 7 QTLs for PH, 12 QTLs for TGW, and 9 QTLs for SL, which explained 3.0–48.8% of the phenotypic variation. Kompetitive Allele Specific PCR (KASP) markers were developed based on sequencing data and used for validation of the stably detected QTLs on chromosomes 3A, 4B and 6A using 400 RILs. A QTL cluster on chromosome 4B for PH and TGW was delimited to a 0.8 Mb physical interval explaining 12.2–22.8% of the phenotypic variation. Gene annotations and analyses of SNP effects suggested that a gene encoding protein Photosynthesis Affected Mutant 68, which is essential for photosystem II assembly, is a candidate gene affecting PH and TGW. In addition, the QTL for HD on chromosome 3A was narrowed down to a 2.5 Mb interval, and a gene encoding an R3H domain-containing protein was speculated to be the causal gene influencing HD. The linked KASP markers developed in this study will be useful for marker-assisted selection in wheat breeding, and the candidate genes provide new insight into genetic study for those traits in wheat.

Background In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) began in Wuhan, China, and led to a global epidemic. We aimed to compare the clinical and serological features of COVID-19 patients with positive and negative reverse transcriptase polymerase chain reaction (RT-PCR) tests. Methods This was a retrospective cohort study conducted from 9 February to 4 April 2020. COVID-19 patients at Leishenshan Hospital in Wuhan, China (125 total cases; 87 RT-PCR positive and 38 RT-PCR negative) were included. COVID-19 serology was assessed by colloidal gold assay. All cases were analyzed for demographic, clinical, and serological features. Results There were no significant differences in most demographic features, clinical symptoms, complications or treatments of RT-PCR positive and negative COVID-19 patients. Serum IgM/IgG was positive in 82 (94%) and 33 (87%) RT-PCR positive and negative cases, respectively. IgM was detectable as early as 3 days after symptom onset and was undetectable 60 days after symptom onset. By contrast, IgG could be detected only 10 days after symptom onset and reached its peak 60 days after symptom onset. Conclusions Serological tests performed during the appropriate time window of disease progression could be valuable auxiliary methods to RT-PCR in COVID-19 patients.

Previous studies reported abnormal spontaneous neural activity in Parkinson’s disease (PD) patients using resting-state functional magnetic resonance imaging (R-fMRI). However, the frequency-dependent neural activity in PD is largely unknown. Here, 35 PD patients and 35 age- and education-matched healthy controls (HCs) underwent R-fMRI scanning to investigate abnormal spontaneous neural activity of PD using the amplitude of low-frequency fluctuation (ALFF) approach within the conventional band (typical band: 0.01–0.08 Hz) and specific frequency bands (slow-5: 0.010–0.027 Hz and slow-4: 0.027–0.073 Hz). Compared with HCs, PD patients exhibited increased ALFF in the parieto-temporo-occipital regions, such as the bilateral inferior temporal gyrus/fusiform gyrus (ITG/FG) and left angular gyrus/posterior middle temporal gyrus (AG/pMTG), and displayed decreased ALFF in the left cerebellum, right precuneus, and left postcentral gyrus/supramarginal gyrus (PostC/SMG) in the typical band. PD patients showed greater increased ALFF in the left caudate/putamen, left anterior cingulate cortex/medial superior frontal gyrus (ACC/mSFG), left middle cingulate cortex (MCC), right ITG, and left hippocampus, along with greater decreased ALFF in the left pallidum in the slow-5 band, whereas greater increased ALFF in the left ITG/FG/hippocampus accompanied by greater decreased ALFF in the precentral gyrus/PostC was found in the slow-4 band (uncorrected). Additionally, the left caudate/putamen was positively correlated with levodopa equivalent daily dose (LEDD), Hoehn and Yahr (HY) stage, and disease duration. Our results suggest that PD is related to widespread abnormal brain activities and that the abnormalities of ALFF in PD are associated with specific frequency bands. Future studies should take frequency band effects into account when examining spontaneous neural activity in PD.

Background: The coronavirus disease 2019 (COVID-19) has been rapidly transmitted worldwide, which contributed to various psychological problems (such as fear, depression, and anxiety) among the general population in China. The purpose of this study is to investigate the prevalence and associated factors of depressive symptoms among Chinese adults.Methods: A cross-sectional study of Chinese adults was conducted during 17–29 February 2020. Symptoms of depression were assessed using the Center for Epidemiologic Studies Depression scale (CES-D).Results: A total of 3,399 respondents were included in the analysis. It was observed that 14.2% (481/3,399) of the participants were screened positive for depressive symptoms. In a multivariate logistic regression analysis, older age (OR = 0.98; 95% CI, 0.97–0.99), smoking (OR = 1.57; 95% CI, 1.10–2.26), self-rated health (good: OR = 0.49; 95% CI, 0.37–0.66; fairly: OR = 0.60; 95% CI, 0.45–0.80), having greater support scores (OR = 0.95; 95% CI, 0.94–0.96), knowledge about the main symptom of COVID-19 (very clearly: OR = 0.58; 95% CI, 0.42–0.79; relatively clearly: OR = 0.59; 95% CI, 0.44–0.79), and staying in Wuhan within 3 months before the outbreak of epidemic (OR = 1.78; 95% CI, 1.34–2.38) were associated with depressive symptoms.Conclusion: A considerable proportion of the general population in China had depressive symptoms during the COVID-19 epidemic. Routine screening and targeted interventions for depression are needed among high-risk depressed individuals during the COVID-19 epidemic.

Technology is an instrument to build BRI relationships, mitigate the environmental and climate impacts of BRI projects, as well as to enhance environmental sustainability in the regions. This study aims to reposition China in global climate technology transfer in BRI era and to obtain initial knowledge on needs, priorities, and barriers from the receivers’ perspective. Focus group method with aid of questionnaire survey and follow-up face-to-face interviews was adopted to capture the major issues directly expressed by receivers from these countries. A total of 63 valid questionnaires were collected, and 13 respondents were face-to-face interviewed. The results confirmed that energy and agriculture were the most prioritized sectors for mitigation and adaptation in the developing countries alongside OBOR. The prioritized technologies for mitigation included cogeneration, solar photovoltaic, and biomass/biogas electricity. Irrigation, conservation agriculture, and soil management were prioritized for adaptation in agricultural sector, and water recycling and reuse, source water protection, and urban drainage management in water resource sector. Technology cost during installation and operation was stressed as the most important factor constraining the application and diffusion of climate technologies. But communication including language, information, and ways of communication, was also identified as an important factor. This implied that the conventional climate technology transfer need adapt to changing contexts of BRI and be complemented with innovative approaches involving multi-actors in different phases of climate technology development. Due to the limited representativeness of the sample, the results can hardly be generalized to all the countries, but raised interesting topics for future researches.

ο-benzoquinone is a common intermediate which is mostly formed by the oxidation of phenolics or polyphenols containing catechol structure. ο-benzoquinone has an outstanding nucleophilic ability, while advanced glycation end products (AGEs) are nucleophilic and can undergo a nucleophilic addition reaction with ο-benzoquinone to mitigate the harmful effects of AGEs on the body. As common nucleophilic substances, amino acids existing in large quantities in food processing and in vivo may bind competitively with ο-benzoquinone, thus influencing the trapping of ο-benzoquinone with AGEs. In this study, cyclic voltammetry and coexistence experiments were used to compare the reactivities of Nε-(carboxymethyl) lysine (CML) and amino acids with 4-methylbenzoquinone (4-MBQ). The results showed that CML is more reactive with ο-benzoquinone than most amino acids, and even in complex systems, ο-benzoquinone still captured CML. Moreover, almost all adducts were identified by UPLC-QTOF-MS/MS, and their chemical formulas were deduced. Quantum chemistry accurately predicts the efficiency and site of reactions of ο-benzoquinone and nucleophiles to a certain extent, and found that a secondary amine has a greater reactivity with 4-MBQ than a primary amine in a similar molecular structure. In general, ο-benzoquinone could capture AGEs, thereby showing potential to reduce the harmfulness of AGEs.

Crack initiation and propagation is a long-standing difficulty in solid mechanics, especially for elastic brittle materials. A new type of transparent sandwich structure, with a magnesium–aluminum spinel ceramic glass as the outer structure, was proposed in this paper. Its dynamic response was studied by high-speed impact experiments and numerical simulations of peridynamics under impact loads, simultaneously. In the experiments, a light gas cannon was used to load the projectile to 180 m/s, and the front impacted the transparent sandwich structure. In the numerical simulations, the discontinuous Galerkin peridynamics method was adopted to investigate the dynamic response of the transparent sandwich structure. We found that both the impact experiments and the numerical simulations could reproduce the crack propagation process of the transparent sandwich structure. The radial cracks and circumferential cracks of the ceramic glass layer and the inorganic glass layer were easy to capture. Compared with the experiments, the numerical simulations could easily observe the damage failure of every layer and the splashing of specific fragments of the transparent sandwich structure. The ceramic glass layer and the inorganic glass layer absorbed the most energy in the impact process, which is an important manifestation of the impact resistance of the transparent sandwich structure.

The flow channel design of bipolar plates plays a significant role in the proton exchange membrane fuel cells operation, particularly in thermal and water management. The pursuit of low-pressure drop supply and flow field uniformity in PEM fuel cells has not stopped, resulting in numerous new bipolar plate flow channel designs. The biomimetic leaf vein shape-based flow channel and lung flow channel designs can significantly improve gas supply uniformity and reduce pressure drop. Therefore, we propose a snowflake-shaped bionic channel design by integrating the advantages of the leaf vein shape and lung shape channel. A 3D multi-physics fuel cell model is used to verify the feasibility and superiority of the bionic snowflake design in improving fuel cell performance, especially in reducing the pumping work. The local pressure distribution, oxygen distribution, water distribution, and current density distribution are used to reveal the enhancement mechanism of the new snowflake flow channel. The flow uniformity is further enhanced by using multi-objective (13 target parameters) and multi-parameter (18 independent variables) genetic algorithm optimization. The general goal of this work is to provide a new strategy for the thermal and water management of PEM fuel cells.

Six novel mycoviruses that collectively represent the mycovirome of Rhizoctonia solani anastomosis group (AG)-3 PT strain ZJ-2H, which causes potato black scurf, were identified through metatranscriptome sequencing and putatively designated as Rhizoctonia solani fusarivirus 4 [RsFV4, positive single-stranded RNA (+ssRNA)], Rhizoctonia solani fusarivirus 5 (RsFV5, +ssRNA), Rhizoctonia solani mitovirus 40 (RsMV40, +ssRNA), Rhizoctonia solani partitivirus 10 [RsPV10, double-stranded RNA (dsRNA)], Rhizoctonia solani partitivirus 11 (RsPV11, dsRNA), and Rhizoctonia solani RNA virus 11 (RsRV11, dsRNA). Whole genome sequences of RsFV4, RsMV40, RsPV10, RsPV11, and RsRV11, as well as a partial genome sequence of RsFV5, were obtained. The 3’- and 5’- untranslated regions of the five mycoviruses with complete genome sequences were folded into stable stem-loop or panhandle secondary structures. RsFV4 and RsFV5 are most closely related to Rhizoctonia solani fusarivirus 1 (RsFV1), however, the first open reading frame (ORF) of RsFV4 and RsFV5 encode a hypothetical protein that differs from the first ORF of RsFV1, which encodes a helicase. We confirmed that RsPV10 and RsPV11 assemble into the spherical virus particles (approximately 30 nm in diameter) that were extracted from strain ZJ-2H. This is the first report that +ssRNA and dsRNA viruses co-infect a single strain of R. solani AG-3 PT.

Pelargonidin-3-O-glucoside (Pg) is a well-known anthocyanin derivative possessing potential biological activity. Nonetheless, the bioactivity of Pg is limited due to instability in the physiological environment. Functionalized nanoliposomes using chitosan and/or pectin coating is an excellent carrier system for nanoencapsulation of food bioactive compounds such as Pg. Therefore, this study aimed to investigate the protective effect of Pg-loaded pectin–chitosan coated nanoliposomes against palmitic acid (PA)-induced hepatocytes injury in L02 cells. Firstly, Pg-loaded pectin–chitosan coated nanoliposomes were characterized using the DLS, HPLC, TEM, and cellular uptake study in L02 cells. Thereafter, we assayed the protective effect against PA-induced lipotoxicity, ROS and O2•− generation, mitochondrial dysfunction (MMP), and GSH depletion. Results showed that Pg-loaded nanoliposomes significantly reduced the PA-induced L02 cells toxicity via suppressing ROS production, O2•− generation, MMP collapse, and GSH reduction, whereas the free-Pg samples were not effective. On the contrary, the chitosan and/or pectin coated nanoliposomes showed higher results compared to coating-free nanoliposomes. Altogether, the results of our study ensured that Pg-loaded pectin–chitosan coated nanoliposomes was capable of reducing PA-induced hepatocytes injury. Thus, pectin–chitosan coated nanoliposomes can be useful for hepatocellular delivery of hydrophilic compounds with greater biological activity.