The genus Amphinemura belongs to the family Nemouridae (Plecoptera) and has 205 species in the Holarctic and Oriental Regions. We sequenced the fourth complete mitochondrial genome of A. bulla Shimizu, 1997. The mitogenome is 15,827 bp long with 37 genes plus a control region with an A + T content of 68.9%. There are 10 intergenic spacers (75 bp total) and 13 gene overlaps (43 bp total). All protein-coding genes (PCGs) use normal initiation codons, except ND1 and ND5 which begin with TTG and GTG. Two PCGs (COII and ND5) use a single T as a partial termination codon. Phylogenetic analyses showed that Nemoura and Amphinemura were sister group resulting in a paraphyletic Amphinemurinae different from the morphological classification.

Neuropathic pain causes great distress among patients; however, its response to traditional analgesia techniques remains sub-optimal. There has been progress in stem cell research for neuropathic pain treatment; however, effective homing remains problematic. This study aimed to establish Fe3O4@polydopamine(PDA)-labeled mesenchymal stem cells (MSCs); moreover, we aimed to guide MSCs using a magnetic field to the spinal cord segments showing pain-related responses to allow MSC homing and gathering, in advance, in order to fully employ their repair function.

Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo + NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and could significantly promote their proliferation, migration, and angiogenesis both in vitro and in vivo. Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration-related chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo + NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo + NPs with magnetic guidance significantly increased the number of Exo + NPs that accumulated at the injury site. Furthermore, these accumulated Exo + NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo; moreover, they reduced scar formation and increased CK19, PCNA, and collagen expression in vivo. Collectively, these findings confirm the development of therapeutically efficacious extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.

Heilongjiang Province is a high-quality japonica rice cultivation area in China. One in ten bowls of Chinese rice is produced here. Increasing yield is one of the main aims of rice production in this area. However, yield is a complex quantitative trait composed of many factors. The purpose of this study was to determine how many genetic loci are associated with yield-related traits. Genome-wide association studies (GWAS) were performed on 450 accessions collected from northeast Asia, including Russia, Korea, Japan and Heilongjiang Province of China. These accessions consist of elite varieties and landraces introduced into Heilongjiang Province decade ago.

21-deoxycortisol (21-DF) is the key intermediate to manufacture pharmaceutical glucocorticoids. Recently, a Japan patent has realized 21-DF production via biotransformation of 17-hydroxyprogesterone (17-OHP) by purified steroid 11β-hydroxylase CYP11B1. Due to the less costs on enzyme isolation, purification and stabilization as well as cofactors supply, whole-cell should be preferentially employed as the biocatalyst over purified enzymes. No reports as so far have demonstrated a whole-cell system to produce 21-DF. Therefore, this study aimed to establish a whole-cell biocatalyst to achieve 21-DF transformation with high catalytic activity and product specificity.

Diabetic retinopathy (DR), a major cause of blindness in working-age people, is attributed to the inflammatory response of retinal Müller cells (RMCs). The heparanase inhibitor PG545 plays proautophagic and anti-inflammatory roles. Intraperitoneal injection of PG545 at a dose of 20 mg/kg/d clearly reduced diabetes-induced body weight changes and fasting blood glucose levels in mice. PG545 also mitigated the reduction in retinal thickness and the formation of microaneurysms by promoting autophagy to inhibit the inflammatory response. In vitro, PG545 stimulated autophagy to downregulate the inflammatory response in high glucose-induced primary adult mouse RMCs. These data suggest that PG545 mitigates DR by promoting RMC autophagy to inhibit the inflammatory response.

We sequenced the complete mitochondrial genomes of Togoperla limbata which is the unique species distributed in Japan to provide supplementary data for future study in phylogenetic studies of Perlidae. This complete mitogenome of T. limbata is 15,915 bp long, including 37 typical genes and a control region as other stoneflies. Through the data analysis, the A + T content of the whole mitogenome, PCGs, tRNAs, rRNAs, and control region was 63.7%, 61.3%, 68.7%, 66.8%, and 74.8%. Most PCGs used typical start or stop codon except COI, ND5, and ND1 used the exceptional start codon and the COII and ND5 used the single T as the stop codon. Phylogenetic tree was constructed by using Bayesian inference (BI) and maximum-likelihood (ML) analysis based on the sequences of the 13 PCGs and two rRNAs and the result showed that subfamily Perlinae was a monophyletic group and the clade Togoperla and Paragnetina had a closer relationship.

Echinococcosis is a zoonotic parasitic disease causing serious health problems in both humans and animals in different endemic regions across the world. There are two different forms of human echinococcosis: Cystic Echinococcosis (CE) and Alveolar Echinococcosis (AE). CE is caused by the larval stage of Echinococcus granulosus sensu lato and AE by the larval stage of Echinococcus multilocularis. Geographically, CE is universally distributed, while AE is prevalent in the northern hemisphere. Although the disease is endemic in neighboring countries (China, Iran and India) of Pakistan, there are limited reports from that country. Besides, there are no comprehensive data on the genotyping of Echinococcus species in humans based on sequence analysis. This study aimed to detect the presence of human CE and to identify Echinococcus spp. in human isolates through genetic characterization of hydatid cysts in the Punjab Province of Pakistan.

Hepatitis B virus (HBV) infection is difficult to cure owing to the persistence of covalently closed circular viral DNA (cccDNA). We performed single-cell transcriptome analysis of newly established HBV-positive and HBV-negative hepatocellular carcinoma cell lines and found that dedicator of cytokinesis 11 (DOCK11) was crucially involved in HBV persistence. However, the roles of DOCK11 in the HBV lifecycle have not been clarified.

Developing artificial porous systems with high molecular recognition performance is critical but very challenging to achieve selective uptake of a particular component from a mixture of many similar species, regardless of the size and affinity of these competing species. A porous platform that integrates multiple recognition mechanisms working cooperatively for highly efficient guest identification is desired. Here, we designed a flexible porous coordination polymer (PCP) and realised a corrugated channel system that cooperatively responds to only target gas molecules by taking advantage of its stereochemical shape, location of binding sites, and structural softness. The binding sites and structural deformation act synergistically, exhibiting exclusive discrimination gating (EDG) effect for selective gate-opening adsorption of CO2 over nine similar gas molecules, including N2, CH4, CO, O2, H2, Ar, C2H6, and even higher-affinity gases such as C2H2 and C2H4. Combining in-situ crystallographic experiments with theoretical studies, it is clear that this unparalleled ability to decipher the CO2 molecule is achieved through the coordination of framework dynamics, guest diffusion, and interaction energetics. Furthermore, the gas co-adsorption and breakthrough separation performance render the obtained PCP an efficient adsorbent for CO2 capture from various gas mixtures.

For the development of antiviral agents to eliminate hepatitis B virus (HBV), it is essential to establish an HBV cell culture system that can easily monitor HBV infection. Here, we created a novel HBV infection monitoring system using a luminescent 11-amino acid reporter, the high-affinity subunit of nano-luciferase binary technology (HiBiT). The HiBiT-coding sequence was inserted at the N-terminus of preS1 in a 1.2-fold plasmid encoding a genotype C HBV genome. After transfection of HepG2 cells with this HiBiT-containing plasmid, the supernatant was used to prepare a recombinant cell culture-derived virus (HiBiT-HBVcc). Primary human hepatocytes (PXB) were inoculated with HiBiT-HBVcc. Following inoculation, intracellular and extracellular HiBiT activity and the levels of various HBV markers were determined. Reinfection of naive PXB cells with HiBiT-HBVcc prepared from HiBiT-HBVcc-infected PXB cells was analyzed. When PXB cells were infected with HiBiT-HBVcc at several titers, extracellular HiBiT activity was detected in a viral titer-dependent manner and was correlated with intracellular HiBiT activity. Inhibitors of HBV entry or replication suppressed extracellular HiBiT activity. Viral DNA, RNA, and proteins were detectable, including covalently closed circular DNA, by Southern blot analysis. The synthesis of relaxed-circular DNA from single-stranded DNA in HiBiT-HBV decreased to one third of that of wild-type HBV, and the infectivity of HiBiT-HBVcc decreased to one tenth of that of wild-type HBVcc. HiBiT-HBVcc prepared from PXB cells harboring HiBiT-HBV was able to infect naive PXB cells. Conclusions: Recombinant HiBiT-HBV can undergo the entire viral life cycle, thus facilitating high-throughput screening for HBV infection in vitro using supernatants. This system will be a powerful tool for developing antiviral agents.

HBV infection causes chronic liver disease and leads to the development of HCC. To identify host factors that support the HBV life cycle, we previously established the HC1 cell line that maintains HBV infection and identified host genes required for HBV persistence.

Hepatitis B virus (HBV) infection is a major global health problem with no established cure. Dedicator of cytokinesis 11 (DOCK11), known as a guanine nucleotide exchange factor (GEF) for Cdc42, is reported to be essential for the maintenance of HBV. However, potential therapeutic strategies targeting DOCK11 have not yet been explored. We have previously developed an in vitro virus method as a more efficient tool for the analysis of proteomics and evolutionary protein engineering. In this study, using the in vitro virus method, we screened and identified a novel antiasialoglycoprotein receptor (ASGR) antibody, ASGR3-10M, and a DOCK11-binding peptide, DCS8-42A, for potential use in HBV infection. We further constructed a fusion protein (10M-D42AN) consisting of ASGR3-10M, DCS8-42A, a fusogenic peptide, and a nuclear localization signal to deliver the peptide inside hepatocytes. We show using immunofluorescence staining that 10M-D42AN was endocytosed into early endosomes and released into the cytoplasm and nucleus. Since DCS8-42A shares homology with activated cdc42-associated kinase 1 (Ack1), which promotes EGFR endocytosis required for HBV infection, we also found that 10M-D42AN inhibited endocytosis of EGFR and Ack1. Furthermore, we show 10M-D42AN suppressed the function of DOCK11 in the host DNA repair system required for covalently closed circular DNA synthesis and suppressed HBV proliferation in mice. In conclusion, this study realizes a novel hepatocyte-specific drug delivery system using an anti-ASGR antibody, a fusogenic peptide, and DOCK11-binding peptide to provide a novel treatment for HBV.

It is not unclear whether the complement system is involved in the pathogenesis of diabetic nephropathy (DN). We explored the role of the complement system in glomeruli from patients with DN using integrated transcriptomic bioinformatics analysis and renal histopathology.

Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non-endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a marker of recent exposure to P. vivax in epidemiological studies.

We aimed to examine the association of three mineral metabolism markers, including serum calcium, inorganic phosphorus, and intact parathyroid hormone with the risk of chronic kidney disease (CKD) at all stages.

Phylogeographic patterns of some extant plant and vertebrate species have been well studied; however, they are poorly understood in the majority of insects. The study documents analysis of mitochondrial (COI, CYTB and ND5) and nuclear (5.8S rDNA, ITS2 and 28S rDNA) data from 419 individuals of Adelphocoris suturalis, which is one of the main cotton pests found in the 31 locations in China and Japan involved in the study. Results show that the species is highly differentiated between populations from central China and peripheral China regions. Analysis of molecular variance showed a high level of geographical differentiation at different hierarchical levels. Isolation-by-distance test showed no significant correlation between genetic distance and geographical distance among A. suturalis populations, which suggested gene flow is not restricted by distance. In seven peripheral populations, the high levels of genetic differentiation and the small Nem values implied that geographic barriers were more likely restrict gene flow. Neutrality tests and the Bayesian skyline plot suggested population expansion likely happened during the cooling transition between Last Interglacial and Last Glacial Maximum. All lines of evidence suggest that physical barriers, Pleistocene climatic oscillations and geographical heterogeneity have affected the population structure and distribution of this insect in China.

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy.

Diet and exercise are the most effective approaches used to induce weight loss. D‑psicose is a low‑calorie sweetener that has been shown to reduce weight in obese individuals. However, the effect of D‑psicose on muscle cells under oxidative stress, which is produced during exercise, requires further investigation. The present study aimed to determine the effects of D‑psicose on C2C12 myogenic cells in vitro. Hydrogen peroxide (H2O2) was used to stimulate the generation of intracellular reactive oxygen species (ROS) in muscle cells to mimic exercise conditions. Cell viability was analyzed using a MTT assay and flow cytometry was used to analyze the levels of apoptosis, mitochondrial membrane potential (MMP), the generation of ROS and the cell cycle distribution following treatment. Furthermore, protein expression levels were analyzed using western blotting and cell proliferation was determined using a colony formation assay. The results of the present study revealed that D‑psicose alone exerted no toxicity on C2C12 mouse myogenic cells. However, in the presence of low‑dose (100 µM) H2O2‑induced ROS, D‑psicose induced C2C12 cell injury and significantly decreased C2C12 cell viability in a dose‑dependent manner. In addition, the levels of apoptosis and the generation of ROS increased, while the MMP decreased. MAPK family molecules were also activated in a dose‑dependent manner following treatment. Notably, the combined treatment induced G2/M phase arrest and reduced the proliferation of C2C12 cells. In conclusion, the findings of the present study suggested that D‑psicose may induce toxic effects on muscle cells in a simulated exercise situation by increasing ROS levels, activating the MAPK signaling pathway and disrupting the MMP.

The coronavirus disease 2019 (COVID-19) pandemic has spread globally. Therapeutic options including antivirals, anti-inflammatory compounds, and vaccines are still under study. Convalescent plasma(CP) immunotherapy was an effective method for fighting against similar viral infections such as SARS-CoV, and MERS-CoV. In the epidemic of COVID-19, a large number of literatures reported the application of CP. However, there is controversy over the efficacy of CP therapy for COVID-19. This systematic review was designed to evaluate the existing evidence and experience related to CP immunotherapy for COVID-19.