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Light is an essential natural factor of fish growth and development. A light regime in indoor aquaculture is critical for sustainable fish production. This research aimed to investigate the effect of light intensity and photoperiod on the growth performance and stress response of Nile tilapia (Oreochromis niloticus), which is an important commercial species, in a recirculating aquaculture system (RAS). Fingerlings with an average weight of 5 ± 0.9 g were randomly assigned to nine 1.5 m3 tanks with 145 fish in each tank, cultured under different light intensities (1000, 2000, and 3000 lx) and photoperiods (12L:12D, 18L:6D, 24L:0D), and fed to apparent satiation twice a day for 160 days. The growth of tilapia subjected to 2000 lx was significantly better than that exposed to 1000 and 3000 lx (P 0.05). Light intensity and photoperiod manipulation did not cause a significant chronic stress response in tilapia. This study demonstrated that light intensity, especially at 2000 lx, and photoperiod manipulation could stimulate the growth of tilapia in the RAS and significantly affect economic profitability. This study also served as an important reference for tilapia indoor aquaculture.

Low temperature in early spring impairs wheat growth and grain yield. However, little is known about the cytological and molecular mechanisms underlying low temperature regulation of wheat spike development. Microstructure observation and transcriptome sequencing of wheat spikes under low temperature were conducted. Low temperature slowed spike development, reduced the yield-component parameters of wheat spikes at the harvest stage, delayed the formation of lateral spikelets and tissue development, and induced the early differentiation of terminal spikelets. Low temperature increased the content of abscisic acid and caused the upregulation of genes in the abscisic acid signaling pathway, including those encoding PP2Cs, SnRK2s, and bZIP transcription factors. Low temperature also induced the upregulation of 33 cold-responsive genes involved in wheat response to low-temperature stress and regulation of abscisic acid biosynthesis and metabolism of other substances. The wheat spike adapted to cold conditions by changing the expression levels of genes involved in spike morphogenesis, including the transcription-factor genes MADS6, ERF4, ERF78, WOX6, and NAC48. These findings suggest that low temperature in early spring delays wheat spike development by increasing abscisic acid content or affecting the expression of genes involved in morphogenesis.

Thermosensitive genic male sterile (TGMS) wheat lines are the core of two-line hybrid systems. Understanding the mechanism that regulates male sterility in TGMS wheat lines is helpful for promoting wheat breeding. Several studies have obtained information regarding the mechanisms associated with male sterility at the transcriptional level, but it is not clear how the post-transcriptional process of alternative splicing might contribute to controlling male sterility. In this study, we performed genome-wide analyses of alternative splicing during the meiosis stage in TGMS line BS366 using PacBio and RNA-Seq hybrid sequencing. Cytological observations indicated that cytoskeleton assembly in pollen cells, calcium deposition in pollen and tapetal cells, and vesicle transport in tapetal cells were deficient in BS366. According to our cytological findings, 49 differentially spliced genes were isolated. Moreover, 25 long non-coding RNA targets and three bHLH transcription factors were identified. Weighted gene co-expression network analysis detected four candidate differentially spliced genes that had strong co-relation with the seed setting percentage, which is the direct representation of male sterility in BS366. In this study, we obtained comprehensive data regarding the alternative splicing-mediated regulation of male sterility in TGMS wheat. The candidates identified may provide the molecular basis for an improved understanding of male sterility.

Captive conditions can affect the symbiotic microbiome of animals. In this study, we compared the structural and functional differences of the gastrointestinal microbiomes of wild Bactrian camels (Camelus ferus) between wild and captive populations, as well as their different host energy utilization performances through metagenomics. The results showed that wild-living camels harbored more microbial taxa related to the production of volatile fatty acids, fewer methanogens, and fewer genes encoding enzymes involved in methanogenesis, leading to higher energy utilization efficiency compared to that of captive-living camels. These findings suggest that the wild-living camel fecal microbiome demonstrates a series of adaptive characteristics that enable the host to adjust to a relatively barren field environment. Our study provides novel insights into the mechanisms of wildlife adaptations to habitats from the perspective of the microbiome.

Suitable reference genes are one of the necessary conditions for obtaining reliable results by real-time fluorescence quantitative PCR (qPCR). In this study, the expression of the 10 common candidate reference genes (18s rRNA, rps27, cnbp, rpl7, ube2, hsp-at, gapdh, β-actin, rpl13a, 1-ef1a) at different developmental stages of gonad and embryo of Takifugu bimaculatus were analyzed by qPCR. And the expression stability of these reference genes is analyzed by GeNorm, NormFinder and Bestkeeper softwares. The results showed that the expression stability of 1-ef1a was the highest (p

Early tuberization, a short period from stolon occurrence to tuber formation, is one of the major characteristics of a good early-maturing potato cultivar, while the regulatory mechanism of tuberization time (TT) is still unclear. In this study, two tetraploid cultivars, Zhongshu 3 (Z3) and Zhongshu 18 (Z18), with short and long TT respectively, were examined to reveal regulatory genes related to TT using RNA sequencing of tissue samples taken during stolon occurrence, stolon swelling and tuber formation. Cluster analysis showed that the gene expression patterns at the stolon swelling and tuber formation stages were significantly different from those at stolon occurrence in both Z3 and Z18. Therefore, we screened the differentially expressed genes (DEGs) at stolon swelling and tuber formation and compared them to those at stolon occurrence. A total of 3 085 DEGs were specifically identified and analyzed according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment, and DEGs involved in starch and sucrose metabolism, plant hormone signal transduction and plant circadian clock were significantly enriched. The circadian clock genes were significantly differentially expressed between Z3 and Z18, revealing an important role for the plant circadian pathway in regulating TT. Furthermore, three candidate genes, StGI, StPRR and StEFM involved in circadian regulation and significantly differentially expressed between Z3 and Z18, were discovered and confirmed by qRT-PCR. The results provide valuable information for understanding the regulatory mechanisms of potato TT and represent a step toward breeding early-maturing potato cultivars.

OBJECTIVE: To explore susceptibility loci associated with uveitis in Behçet's disease (BD).METHODS: We conducted a 2-stage study, consisting of a genome-wide association study (GWAS) stage and a replication stage, in a Chinese population. The GWAS stage included 978 cases with BD-related uveitis and 4,388 controls, and the replication stage included 953 cases with BD-related uveitis and 2,129 controls. Luciferase reporter analysis and chromatin immunoprecipitation assay were performed to explore the functional role of susceptibility genetic variants near ZMIZ1.RESULTS: Three independent HLA alleles (HLA-B51 [3.75 × 10-190 ], HLA-A26 [1.50 × 10-18 ], and HLA-C0704 [3.44 × 10-16 ]) were identified as having a genome-wide association with BD-related uveitis. In the non-HLA region, in addition to confirming 7 previously reported loci, we identified 22 novel susceptibility variants located in 16 loci. Meta-analysis of the Chinese cohort consisting of 1,931 cases and 6,517 controls and a published Japanese cohort of 611 cases and 737 controls showed genome-wide significant associations with ZMIZ1, RPS6KA4, IL10RA, SIPA1-FIBP-FOSL1, and VAMP1. Functional experiments demonstrated that genetic variants of ZMIZ1 were associated with enhanced transcription activity and increased expression of ZMIZ1.CONCLUSION: This GWAS study identified a novel set of genetic variants that are associated with susceptibility to uveitis in BD. These findings enrich our understanding of the contribution of genetic factors to the disease.

MEN1, which encodes menin protein, is the most frequently mutated gene in pancreatic neuroendocrine neoplasms (pNEN). Pleiotrophin (PTN) has been reported as a downstream factor of menin that promotes metastasis in different tumor entities. In this study, the effect of menin and its link to PTN were assessed using features of pNEN cells and the outcome of patients with pNEN. The expression levels of menin and PTN in tissues from patients with pNEN were examined using qRT-PCR and western blot and compared with their metastasis status. Functional assays, including transwell migration/invasion and scratch wound-healing assays, were performed on specifically designed CRISPR/Cas9-mediated MEN1-knockout (MEN1-KO) pNEN cell lines (BON1

Mesenchymal stem cells (MSCs), multipotent stromal cells, have attracted extensive attention in the field of regenerative medicine and cell therapy due to the capacity of self-renewal, multilineage differentiation, and immune regulation. MSCs have different cellular effects in different diseases, and even have markedly different curative effects with different tissue sources, indicating the plasticity of MSCs. The phenotypes, secreted factors, and proliferative, migratory, differentiating, and immunomodulatory effects of MSCs depend on certain mediators present in their microenvironment. Understanding microenvironmental factors and their internal mechanisms in MSC responses may help in subsequent prediction and improvement of clinical benefits. This review highlighted the recent advances in MSC plasticity in the physiological and pathological microenvironment and multiple microenvironmental factors regulating MSC plasticity. It also highlighted some progress in the underlying molecular mechanisms of MSC remodeling in the microenvironment. It might provide references for the improvement in vitro culture of MSCs, clinical application, and in vivo induction.

Synovium has widely participated in induced inflammation, suggesting that it is a potential target to reduce aromatase inhibitors (AIs) causing joint inflammation or pain. Exercise and mechanical stimulation are important strategies for precaution and treatment of bone inflammation. In this work, we developed a novel thermo-sensitive hydrogel, which could be injected intra-articularly. The aim of this research was to investigate the role of various mechanical strength hydrogels in reducing synovium inflammation. The effect of different mechanical strength hydrogels on regulating synovium inflammation was used to stimulate human fibroblast-like synoviocytes (FLS) under a cyclic mechanical compression environment in vitro. Cytokine and metalloprotease expression in FLS was analyzed by the western blot and q-PCR method, in which FLS were cultured with the different mechanical strength hydrogels. The results showed that a moderate-intensity hydrogel mechanical stimulation might be suitable in reducing AI-induced FLS inflammation via the NK-κB pathway. In addition, we built an AI-treated rat model and injected the different mechanical strength hydrogels. Similarly, the moderate-strength mechanical hydrogel could reduce the inflammatory factor and metalloproteinase expression in synovial tissues and intra-articular synovia. Refereed/Peer-reviewed

A pilot-scale multistage constructed wetland-pond (MCWP) system with a "pre-ecological oxidation pond, two-stage horizontal subsurface flow constructed wetland (HSCW) and surface flow constructed wetland (SFCW) as the core and postsubmerged plant pond" as the process was used to treat actual polluted river water in the field, and the variation in nitrogen removal from summer to winter was investigated. The results showed that the average total nitrogen (TN) removal efficiency in the MCWP was approximately 40.74%. The significant positive correlation between the daily highest temperature and the TN removal efficiency of the whole system was fitted with a nonlinear curve (R2 = 0.7192). The TN removal load rate in the HSCWs was 2.7–3.7 times that in the SFCW. The SFCW, which had high-density plants (35 plants/m2), increased the proportion of nitrogen removed by plant harvesting and microbial function. The TN transformed by Iris pseudacorus L. accounted for 54.53% in the SFCW. Furthermore, bacteria completed the nitrogen cycle in the SFCW through a variety of nitrogen removal pathways. This research not only investigated the TN removal performance in an MCWP system but also made it possible to predict the TN removal efficiency according to the daily highest temperature from summer to winter in the field.

Inflammatory bowel diseases (IBD) are chronic inflammatory gastrointestinal diseases characterized by dysregulation of the intestinal epithelial barrier (IEB) and intermittent relapses. Recent data show that the glial cell line-derived neurotrophic factor (GDNF) promotes IEB function and wound healing. Apart from protective effects of GDNF on enteric nervous system and IEB, an immunomodulatory role has been assumed. However, it is inconsistent whether GDNF levels are increased or decreased in the inflamed colon of patients with IBD. Furthermore, GDNF is 1 of 3 protein markers associated with relapse in a prospective cohort study in IBD patients with clinically and endoscopically quiescent disease. Additionally, not only enteric glial cells (EGCs), but also intestinal smooth muscle cells and enterocytes synthesize GDNF in significant amounts; in addition, its receptors are expressed in intestinal neurons, EGCs, immune cells and epithelial cells, which points to a potential auto- or paracrine signaling loop between some of these cells. Whether GDNF is involved in IBD-associated fibrosis and colitis-associated colorectal cancer remains to be confirmed. In this review we aim to summarize and discuss the current knowledge on the effects of GDNF and its potential role in the contribution to the pathogenesis of IBD.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disorder worldwide. Murine models of NAFLD have been widely used to explore its pathogenesis. In this study, we performed a systematic evaluation of hepatic genome-wide mRNA expression by RNA-Sequencing using three mouse models of NAFLD: leptin receptor deficient db/db mice, high-fat high-sugar diet (HSHF)-induced obese mice, and dexamethasone (DEX)-induced NAFLD mice. As a result, we found both distinct and common pathways in the regulation of lipid metabolism from transcriptomes of three mouse models. Moreover, only a total of 12 differentially expressed genes (DEGs) were commonly detected among all three mouse groups, indicating very little overlap among all three models. Therefore, our results suggest that NAFLD is a heterogeneous disease with highly variable molecular mechanisms.

Objective Temporomandibular joint (TMJ) osteoarthritis (OA) is a type of TMJ disorders with clinical symptoms of pain, movement limitation, cartilage degeneration and joint dysfunction. This review article is aiming to summarize recent findings on signaling pathways involved in TMJ OA development and progression. Methods Most recent findings in TMJ OA studies have been reviewed and cited. Results TMJ OA is caused by inflammation, abnormal mechanical loading and genetic abnormalities. The molecular mechanisms related to TMJ OA have been determined using different genetic mouse models. Recent studies demonstrated that several signaling pathways are involved in TMJ OA pathology, including Wnt/β-catenin, TGF-β and BMP, Indian Hedgehog, FGF, NF-κB, and Notch pathways, which are summarized in this review article. Alterations of these signaling pathways lead to the pathological changes in TMJ tissues, affecting cartilage matrix degradation, catabolic metabolism and chondrocyte apoptosis. Conclusion Multiple signaling pathways were involved in the pathological process of TMJ OA. New therapeutic strategies, such as stem cell application, gene editing and other techniques may be utilized for TMJ OA treatment. The translational potential of this article TMJ OA is a most important subtype of TMJ disorders and may lead to substantial joint pain, dysfunction, dental malocclusion, and reduced health-related quality of life. This review article summarized current findings of signaling pathways involved in TMJ OA, including Wnt/β-catenin, TGF-β and BMP, Indian Hedgehog, FGF, NF-κB, and Notch pathways, to better understand the pathological mechanisms of TMJ OA and define the molecular targets for TMJ OA treatment.

Introduction Elimination or blocking of astrocytes could ameliorate neuropathic pain in animal models. MiR-125a-5p, expressed in astrocyte derived extracellular vesicles, could mediate astrocyte function to regulate neuron communication. However, the role of miR-125a-5p in DPN (diabetic peripheral neuropathy) remains elusive. Materials and methods Type 2 diabetic mouse (db/db) was used as DPN model, which was confirmed by detection of body weight, blood glucose, mechanical allodynia, thermal hyperalgesia, glial fibrillary acidic protein (GFAP) and monocyte chemoattractant protein-1 (MCP-1). Astrocyte was isolated from db/db mouse and then subjected to high glucose treatment. The expression of miR-125a-5p in db/db mice and high glucose-induced astrocytes was examined by qRT-PCR analysis. Downstream target of miR-125a-5p was clarified by luciferase reporter assay. Tail vein injection of miR-125a-5p mimic into db/db mice was then performed to investigate role of miR-125a-5p on DPN. Results Type 2 diabetic mice showed higher body weight and blood glucose than normal db/m mice. Thermal hyperalgesia and mechanical allodynia were decreased in db/db mouse compared with db/m mouse, while GFAP and MCP-1 were increased in db/db mouse. High glucose treatment enhanced the protein expression of GFAP and MCP-1 in astrocytes. Sciatic nerve tissues in db/db mice and high glucose-induced astrocytes exhibited a decrease in miR-125a-5p. Systemic administration of miR-125a-5p mimic increased mechanical allodynia and thermal hyperalgesia, whereas it decreased GFAP and MCP-1. TRAF6 (tumor necrosis factor receptor associated factor 6) was validated as target of miR-125a-5p. Conclusion MiR-125a-5p in astrocytes attenuated DPN in db/db mice by up-regulation of TRAF6, which indicated the potential therapeutic effect.

Graphical abstract, Highlights • Facile antigen/adjuvant co-loaded nanovaccine made by convenient green preparation. • The immunological activity of the antigen and adjuvant was maximally preserved. • The minimalist nanovaccine had excellent stability and antitumor immune activation. • Nanovaccine combined with PD-1 antibody synergistically enhanced therapy outcome. • Good practicability for expanding clinical translation and personalized therapy., Introduction Tumor vaccine has been a research boom for cancer immunotherapy, while its therapeutic outcome is severely depressed by the vulnerable in vivo delivery efficiency. Moreover, tumor immune escape is also another intractable issue, which has badly whittled down the therapeutic efficiency. Objectives Our study aims to solve the above dilemmas by cooperating minimalist nanovaccine with PD-1 blockade for effective and feasible cancer immunotherapy. Methods The minimalist antigen and adjuvant co-delivery nanovaccine was developed by employing natural polycationic protamine (PRT) to carry the electronegative ovalbumin (OVA) antigen and unmethylated Cytosine-phosphorothioate-Guanine (CpG) adjuvant via convenient chemical bench-free “green” preparation without chemical-synthesis and no organic solvent was required, which could preserve the immunological activities of the antigens and adjuvants. On that basis, PD-1 antibody (aPD-1) was utilized to block the tumor immune escape and cooperate with the nanovaccine by maintaining the tumoricidal-activity of the vaccine-induced T cells. Results Benefited from the polycationic PRT, the facile PRT/CpG/OVA nanovaccine displayed satisfactory delivery performance, involving enhanced cellular uptake in dendritic cells (DCs), realizable endosomal escape and promoted stimulation for DCs’ maturation. These features would be helpful for the antitumor immunotherapeutic efficiency of the nanovaccine. Furthermore, the cooperation of the nanovaccine with aPD-1 synergistically improved the immunotherapy outcome, profiting by the cooperation of the “T cell induction” competency of the nanovaccine and the “T cell maintenance” function of the aPD-1. Conclusion This study will provide new concepts for the design and construction of facile nanovaccines, and contribute valuable scientific basis for cancer immunotherapy.

SMI-32 is widely used to identify entire populations of alpha retinal ganglion cells (RGCs) and several SMI-32+ RGC subsets have been studied thoroughly in rodents. However, due to the thick cover of SMI-32+ neurofilaments, the morphology of SMI-32+ RGCs in the central retinal region is obscured and rarely described. Moreover, SMI-32 labels more than one morphological RGC type and the full morphological characteristics and distribution of SMI-32+ RGCs have yet to be discovered. Here, using intracellular neurobiotin injections combined with SMI-32 antibody staining, we investigated morphological and distributional properties of the entire SMI-32+ RGCs population in the rat retina. We found that SMI-32+ RGCs were evenly distributed throughout the rat retina. We compared the morphological features of SMI-32+ ON and OFF cells in the central, middle, and peripheral retinal regions. We found that SMI-32+ RGCs in different regions have distinct characteristics, such as the soma area, the dendritic field area and Sholl analysis of ON cells and OFF cells revealed significant differences between each region. We classified SMI-32+ RGCs into five clusters based on morphological features and found that a majority of SMI-32+ RGCs belong to alpha-like cells; however, a small proportion of SMI-32+ RGCs had small soma and small dendritic fields. Together, we present a full description of the morphology and distribution of SMI-32 immunoreactive RGCs in the rat retina. This article is protected by copyright. All rights reserved.

Classically, mitochondrial respiration responds to decreased membrane potential (ΔΨ) by increasing respiration. However, we found that for succinate-energized complex II respiration in skeletal muscle mitochondria (unencumbered by rotenone), low ΔΨ impairs respiration by a mechanism culminating in oxaloacetate (OAA) inhibition of succinate dehydrogenase (SDH). Here, we investigated whether this phenomenon extends to far different mitochondria of a tissue wherein ΔΨ is intrinsically low, i.e., interscapular brown adipose tissue (IBAT). Also, to advance our knowledge of the mechanism, we performed isotopomer studies of metabolite flux not done in our previous muscle studies. In additional novel work, we addressed possible ways ADP might affect the mechanism in IBAT mitochondria. UCP1 activity, and consequently ΔΨ, were perturbed both by GDP, a well-recognized potent inhibitor of UCP1 and by the chemical uncoupler carbonyl cyanide m-chlorophenyl hydrazone (FCCP). In succinate-energized mitochondria, GDP increased ΔΨ but also increased rather than decreased (as classically predicted under low ΔΨ) O

Sequence learning is a ubiquitous facet of human and animal cognition. Here, using a common sequence reproduction task, we investigated whether and how the ordinal and relational structures linking consecutive elements are acquired by human adults, children, and macaque monkeys. While children and monkeys exhibited significantly lower precision than adults for spatial location and temporal order information, only monkeys appeared to exceedingly focus on the first item. Most importantly, only humans, regardless of age, spontaneously extracted the spatial relations between consecutive items and used a chunking strategy to compress sequences in working memory. Monkeys did not detect such relational structures, even after extensive training. Monkey behavior was captured by a conjunctive coding model, whereas a chunk-based conjunctive model explained more variance in humans. These age- and species-related differences are indicative of developmental and evolutionary mechanisms of sequence encoding and may provide novel insights into the uniquely human cognitive capacities.SIGNIFICANCE STATEMENTSequence learning, the ability to encode the order of discrete elements and their relationships presented within a sequence, is a ubiquitous facet of cognition among humans and animals. By exploring sequence-processing abilities at different human developmental stages and in nonhuman primates, we found that only humans, regardless of age, spontaneously extracted the spatial relations between consecutive items and used an internal language to compress sequences in working memory. The findings provided insights into understanding the origins of sequence capabilities in humans and how they evolve through development to identify the unique aspects of human cognitive capacity, which includes the comprehension, learning, and production of sequences, and perhaps, above all, language processing.

OBJECTIVES Hypertension is one of the major adverse effects of tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factors. However, the mechanism underlying TKIs-induced hypertension remains unclear. Here, we explored the role of the RhoA/Rho kinase (ROCK) signaling pathway in elevation of blood pressure (BP) induced by apatinib, a selective TKI approved in China for treatment of advanced or metastatic gastric cancer. A nonspecific ROCK inhibitor, Y27632, was then combined with apatinib and its efficacy in alleviating apatinib-induced hypertension was evaluated. METHODS Normotensive female Wistar-Kyoto rats were exposed to two different doses of apatinib, or apatinib combined with Y27632, or vehicle for 2 weeks. BP was monitored by a tail-cuff plethysmography system. The mRNA levels and protein expression in the RhoA/ROCK pathway were determined, and vascular remodeling assessed. RESULTS Administration of either a high or low dose of apatinib was associated with a rapid rise in BP, reaching a plateau after 12 days. Apatinib treatment mediated upregulation of RhoA and ROCK II in the mid-aorta, more significant in the high-dose group. However, ROCK I expression showed no statistically significant differences. Furthermore, the mRNA level of GRAF3 decreased dose-dependently. Apatinib administration was also associated with decreased levels of MLCP, and elevated endothelin-1 (ET-1) and collagen I, which were accompanied with increased mid-aortic media. However, treatment with Y27632 attenuated the above changes. CONCLUSION These findings suggest that activation of the RhoA/ROCK signaling pathway could be the underlying mechanism of apatinib-induced hypertension, while ROCK inhibitor have potential therapeutic value.

Unlike that of other crops, the growth of tea plants can be promoted by aluminum, but its regulation mechanism remains unclear. Some endophytes can also promote growth of plant hosts. In this paper, tea roots treated with aluminum were used to study the growth-promoting traits and aluminum tolerance of endophytes. Meta-16S rDNA analysis revealed that Burkholderia was enriched in tea roots after aluminum treatment, and it was the dominant strain for hydroponic tea roots and field tea roots. Actinomycetes constituted the dominant strains in hydroponic tea seedlings treated with aluminum. Sixteen endophytic bacteria, including 12 strains of Firmicutes, 2 strains of Proteobacteria and 2 strains of Actinomycetes, were isolated and identified from hydroponic tea roots treated with different aluminum concentrations. Growth-promoting activity analysis showed that the isolated endophytic bacteria all had more than one plant growth-promoting trait. Among them, B4 (Bacillus nealsonii), B8 (Brevibacterium frigoritolerans) and A2 (Nocardia nova) bacteria each had three growth-promoting traits. Aluminum tolerance ability analysis indicated that endophyte A1 (Leifsonia shinshuensis) had the strongest aluminum tolerance ability, up to 200 mg l−1 aluminum. Plant–bacteria interactions showed that endophytes A1, A2 and B4 and their synthetic community all had a growth-promoting effect on the growth of wheat lateral roots. Moreover, endophytes A1 and B4 alleviated aluminum stress in wheat. Endophyte A1 also promoted the growth of tea cuttings, especially lateral roots, with/without aluminum. Taken together, aluminum enhanced the distribution of aluminum-tolerant and growth-promoting bacteria, thereby promoting the growth of tea roots. This study provides a new aspect for research on the mechanism by which aluminum promotes tea plant growth.

Breast cancer (BC) is the most common cancer among women. LINC00675 and miR-513b-5p has been reported to be abnormally expressed in multiple types of cancers and modulate malignant phenotypes of cancer cells. However, to date, the functional role and underlying regulatory mechanism of LINC00675 and miR-513b-5p in BC remains largely unknown. Here, we found that LINC00675 was significantly downregulated in BC tissues and cell lines. Decrease of LINC00675 expression associated with higher tumor grade, lymphovascular invasion and shorter survival in BC patients. Functional experiments demonstrated that overexpression of LINC00675 suppressed BC cell proliferation, migration and invasion, whereas depletion of LINC00675 exerted opposite effects. Mechanistically, LINC00675 functioned as a competing endogenous RNA (ceRNA) to interact with miR-513b-5p and suppress its expression. Moreover, METTL3 increased the m6A methylation of LINC00675, which enhanced the association between LINC00675 and miR-513b-5p. Collectively, the central findings of our study suggest that LINC00675 represses BC progression through the inhibition of miR-513b-5p in a m6A-dependent manner.

Here, we present the complete genome sequence and annotation of Ralstonia syzygii subsp. indonesiensis strain LLRS-1, which caused bacterial wilt on flue-cured tobacco in Yunnan Province, southwest China. Strain LLRS-1 is the first R. syzygii strain identified to be pathogenic to tobacco in China. The completely assembled genome of strain LLRS-1 consists of a 3,648,314-bp circular chromosome and a 2,046,405-bp megaplasmid with 5,190 protein-coding genes, 55 transfer RNAs, 28 small RNAs, 3 structural RNAs (5S, 16S, and 23S), and a G+C content of 67.05%.

Enterocytozoon bieneusi is a common gastrointestinal parasite that has a broad range of hosts, including birds, mammals, and even humans. The changes of gut bacterial communities have been demonstrated during the course of E. bieneusi. This study aimed to examine the infection status, and assess the zoonotic potential and influence of E. bieneusi on gut bacterial communities of captive foxes in Xinxiang, central China. Fecal samples were collected from 216 captive foxes, and amplification of the internal transcribed spacer (ITS) gene of each sample was performed by nested polymerase chain reaction. E. bieneusi was detected in 48 (22.2%) samples, and five previously reported genotypes CHN-F1 (n = 25), D (n = 18), BEB6 (n = 3), NCF2 (n = 1), and CHN-DC1 (n = 1) were identified, with CHN-F1 being the dominant genotype (25/48, 52.1%). Phylogenetic analysis further revealed that CHN-F1, D, NCF2, and CHN-DC1 genotypes belonged to the zoonotic group 1 of E. bieneusi, whereas BEB6 belonged to group 2. Moreover, sequencing and bioinformatics analysis of the V3–V4 region of 16S rRNA gene in five E. bieneusi-positive and five negative samples showed that gut microbial diversity was higher in the infected animals. In both groups, Firmicutes and Bacteroidetes were the two most abundant phyla, but the Firmicutes/Bacteroidetes ratio was lower in E. bieneusi-positive foxes (7.9:1) as compared with E. bieneusi-negative foxes (5:1). More importantly, at the phylum level, “beneficial bacteria” such as Firmicutes (1.6%) and Bacteroides (5.8%) increased, whereas “opportunistic pathogens” such as Fusobacteria (8.2%) decreased. Similarly, at the genus level, the pathogenic Clostridiaceae_Clostridium (10.0%) decreased, whereas the “beneficial bacteria” Lactococcus (6.6%) increased. These interesting phenomena warrant further investigation.

Myiasis is an infestation of maggots on living tissue in humans and animals all over the world. It is known to occur in wild animals, while no information is reported in forest musk deer (Moschus berezovskii). During our research on the conservation of forest musk deer, we found a new record of traumatic myiasis of an injured forest musk deer. The flies are likely Lucilia caesar (Linnaeus, 1758) according to the results of DNA barcoding technology. We report traumatic myiasis of forest musk deer for the first time, which expands the information on parasite and myiasis of forest musk deer and confirms the potential risk of traumatic myiasis of forest musk deer., Graphical abstract Image 1, Highlights • First report of Lucilia caesar parasitizing forest musk deer. • The myiasis caused by Lucilia caesar occurred in China. • This study will provide new epidemiological information of myiasis of wildlife in China.

Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix (ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant Newcastle disease virus (NDV) expressing matrix metalloproteinase (MMP8) (NDV-MMP8) using with reverse genetic technology. In vitro, NDV-MMP8 was identified and verified by WB and ELISA. Cell viability was detected by CCK-8 assay. In vivo, we established two liver cancer xenograft models. NDV-MMP8 was injected into the tumor to observe the tumor volume and survival of mice. The changes in extracellular matrix were observed by Masson's trichrome staining. Virus expression in tumor tissues was detected by immunofluorescence assay. The virus titer in tumor tissues was detected by TCID50. Histopathological changes were detected by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Intratumoral administration of NDV-MMP8 can effectively degrade ECM, promote the spread of the virus within the tumor, and reduce tumor growth rate. Therefore, the method of increasing intratumoral virus accumulation by degradation of the ECM to enhance the oncolytic effect has great potential for clinical application.

Because of the yield increase of 3.5–15% compared to conventional wheat, hybrid wheat is considered to be one of the main ways to greatly improve the wheat yield in the future. In this study, we performed a principal component analysis (PCA) on two-line hybrids wheat and their parents using the grain weight (GW), the length of spike (LS), the kernel number of spike (KSN), and spike number (SPN) as variables. The results showed that the variables could be classified into three main factors, the weight factor (factor 1), the quantity factor 1 (factor 2) and the quantity factor 2 (factor 3), which accounted for 37.1, 22.6 and 18.5%, respectively of the total variance in different agronomic variables, suggesting that the GW is an important indicator for evaluating hybrid combinations, and the grain weight of restorer line (RGW) could be used as a reference for parents selection. The hybrid combination with a higher score in factor 1 direction and larger mid-parent heterosis (MPH) of the GW and its parents were used to carry out the analysis of grain filling, 1-aminocylopropane-1-carboxylicacid (ACC) and polyamine synthesis related genes. The results suggested that the GW of superior grain was significantly higher than that of inferior grains in BS1453×JS1 (H) and its parents. Both grain types showed a weight of H between BS1453 (M) and JS1(R), and a larger MPH, which may be caused by their differences in the active filling stage and the grain filling rate. The ADP-glucose pyrophosphorylase (AGPase), granule bound starch synthase I (GBSSI), starch synthase III (SSS), and starch branching enzyme-I (SBE-I) expression levels of H were intermediated between M and R, which might be closely related to MPH formation of the GW. Compared with R and H, the GW of M at maturity was the lowest. The expression levels of spermidine synthase 2 (Spd2), ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) had significantly positive correlations with the grain filling rate (r=0.77*, 0.51*, 0.59*), suggesting their major roles in the grain filling and heterosis formation. These provide a theoretical basis for improving the GW of photo-thermo-sensitive male sterile lines (PTSMSL) by changing the endogenous polyamine synthesis in commercial applications.

The transcriptional repressor Bmi-1 is involved in cell-cycle regulation and cell senescence, the deficiency of which has been shown to cause oxidative stress. This study investigated whether Bmi-1 deficiency plays a role in promoting disc degeneration and the effect of treatment with antioxidant N-acetylcysteine (NAC) on intervertebral disc degeneration. Bmi-1−/− mice were treated with the antioxidant NAC, supplied in drinking water (Bmi-1−/−+NAC). For in vitro experiments, mouse intervertebral discs were cultured under low oxygen tension and serum-limiting conditions in the presence of tumour necrosis factor α and interleukin 1β in order to mimic degenerative insult. Disc metabolism parameters in these in vitro and in vivo studies were evaluated by histopathological, immunohistochemical and molecular methods. Bmi-1−/− mice showed lower collagen Ⅱ and aggrecan levels and higher collagen Ⅹ levels than wild-type and Bmi-1−/−+NAC mice. Bmi-1−/− mice showed significantly lower superoxide dismutase (SOD)-1, SOD-2, glutathione peroxidase (GPX)-1 and GPX-3 levels than their wild-type littermates and Bmi-1−/−+ NAC mice. Relative to Bmi-1−/− mice, the control and Bmi-1−/−+NAC mice showed significantly lower p16, p21, and p53 levels. These results demonstrate that Bmi-1 plays an important role in attenuating intervertebral disc degeneration in mice by inhibiting oxidative stress and cell apoptosis Refereed/Peer-reviewed

Root architecture is very important for plant growth. In this study, we characterized the process of root formation in grapevine (Vitis vinifera L.). Continuous observation of root morphology during development revealed that the establishment of root system could be divided into five stages: initial cultivation (stage I), preliminary development (stage II), even change (stage III), root system formation (stage IV), and root architecture stability (stage V). The level of abscisic acid (ABA) increased from stages II to IV and was stable at stage V. Quantitative expression analysis of 11 genes encoding ABA-related rate-limiting enzymes in different tissues showed that the expression of VvPYL1 was the highest in roots. Spatiotemporal expression analysis showed that VvPYL1 was highly expressed during stages II and III. Furthermore, VvPYL1 was highly expressed in lateral roots of grapevine seedlings in tissue culture. Overexpression of VvPYL1 in Arabidopsis thaliana resulted in longer root hairs compared with wild-type plants. Moreover, the root hair length of transgenic lines was hypersensitive to exogenously applied ABA. Additionally, VvPYL1 overexpressing plants showed greater drought tolerance and longer root hairs than wild-type plants under osmotic stress. These results suggest that VvPYL1 may play a key role in root development and drought resistance.

Patients treated with immune checkpoint inhibitors (ICIs) often experience unique immune-related adverse events (irAEs), and the previous studies demonstrated an association between irAEs and better outcomes in patients with ICI treatment for advanced non-small cell lung cancer (NSCLC). However, the correlation between the occurrence of mild and severe irAEs and prognosis remains unclear. Additionally, little is known regarding the association between the timing of mild and severe irAEs and clinical outcomes. We retrospectively conducted a multicenter study of advanced NSCLC patients treated with ICI monotherapy. Of the 222 patients, 79 patients (35.6%) experienced at least one irAE, and most were of grade 1 or 2 (mild) (26.6%). The most common irAEs were pneumonitis (n = 21, 9.5%) and skin-related adverse reactions (n = 19, 8.6%). The median progression-free survival of all patients treated with ICIs was 3.2 months. Patients experiencing irAEs had a better prognosis than those without such events (6.5 vs. 2.6 months, p = 0.004), and mild irAEs were associated with the best prognosis. The difference in overall survival between mild and severe irAEs was significant (34.3 vs. 17.3 months, p = 0.021). We further analyzed differences between patients with irAEs occurring at 3 or 6 weeks, and found that the earlier the occurrence of mild irAEs, the better the prognosis; however, the opposite was true for severe irAEs. In summary, patients with early occurring mild irAEs showed better clinical outcomes, whereas those with early severe irAEs tended to show poorer clinical outcomes.

The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized. Here, using a metagenomics-based search strategy, we discovered that bacterial members of the human gut and oral microbiome encode enzymes that selectively phosphorylate a clinically used antidiabetic drug, acarbose1,2, resulting in its inactivation. Acarbose is an inhibitor of both human and bacterial α-glucosidases3, limiting the ability of the target organism to metabolize complex carbohydrates. Using biochemical assays, X-ray crystallography and metagenomic analyses, we show that microbiome-derived acarbose kinases are specific for acarbose, provide their harbouring organism with a protective advantage against the activity of acarbose, and are widespread in the microbiomes of western and non-western human populations. These results provide an example of widespread microbiome resistance to a non-antibiotic drug, and suggest that acarbose resistance has disseminated in the human microbiome as a defensive strategy against a potential endogenous producer of a closely related molecule. Bacteria in the human gut and oral microbiome encode enzymes that selectively phosphorylate the antidiabetic drug acarbose—an inhibitor of both human and bacterial α-glucosidases—resulting in its inactivation and limiting the drug's effects on the ability of the host to metabolize complex carbohydrates.

Insect group h chitinase is a promising target for designing non-target safe pesticides in that it is exclusively distributed in lepidopteran insects, over 80% of which are agricultural pests. In this work, lynamicin B was discovered to be an inhibitor of OfChi-h, the group h chitinase from the lepidopteran pest Ostrinia furnacalis. Lynamicin B was revealed to competitively inhibit OfChi-h with a Ki value of 8.76 μM and does not significantly inhibit other chitinases. The co-crystal structure of lynamicin B and OfChi-h revealed that the dichloroindolyl group of lynamicin B occupies an unexplored pocket below subsites +1 and +2 of the substrate-binding cleft, which is vital for its selectivity. Feeding experiments demonstrated that lynamicin B exhibited high insecticidal activities against other lepidopteran pests Mythimna separata and Spodoptera frugiperda besides O. furnacalis. Moreover, lynamicin B did not affect Trichogramma ostriniae, a natural enemy of O. furnacalis. This study provides a natural-derived potent pesticide for the control of lepidopteran pests, leaving its natural enemy unaffected.

Early detection is essential to improve the survival of lung cancer (LC). The quantitative measurement of specific DNA methylation changes in the peripheral blood could provide an efficient strategy for the detection of early cancer. We applied a candidate approach and assess the association between blood-based SH3BP5 methylation and the risk of lung adenocarcinoma (LUAD) in a case–control cohort. The methylation level of four CpG sites in the promoter of SH3BP5 gene was quantitatively determined by mass spectrometry in 171 very early-stage LUAD patients (93.6% LUAD at stage I) and 190 age and gender-matched controls. The logistic regression and non-parametric tests were used for the statistical analyses. We observed a significant association between decreased methylation of SH3BP5_CpG_4 in the peripheral blood and increased risk of LUAD (odds ratio (OR) per-10% methylation = 1.51, P = 0.006, FDR = 0.024), and even for the LUAD at stage I (OR per-10% methylation = 1.53, P = 0.006, FDR = 0.024). Moreover, the lower quartile of SH3BP5_CpG_4 methylation was correlated with increased risk for LUAD with a P trend of 0.011. Further investigation disclosed that the hypomethylation of SH3BP5_CpG_4 was mostly associated with LUAD in younger subjects (OR per-10% methylation = 2.02, P = 0.010, age

Mutations of the X-linked methyl-CpG-binding protein 2 (MECP2) gene in humans are responsible for most cases of Rett syndrome (RTT), an X-linked progressive neurological disorder. While genome-wide screens in clinical trials have revealed several putative RTT-associated mutations in MECP2, their causal relevance regarding the functional regulation of MeCP2 at the etiologic sites at the protein level requires more evidence. In this study, we demonstrated that MeCP2 was dynamically modified by O-linked-β-N-acetylglucosamine (O-GlcNAc) at threonine 203 (T203), an etiologic site in RTT patients. Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impaired dendrite development and spine maturation in cultured hippocampal neurons, and disrupted neuronal migration, dendritic spine morphogenesis, and caused dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex. Mechanistically, genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreased the neuronal activity-induced induction of Bdnf transcription. Our study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via brain-derived neurotrophic factor. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-021-00784-8.

Background To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs). Methods Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years. Results Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012–2019, with changes ranging from −17.2% for RSV to −87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020–January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children Conclusions Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.

Integrin-linked kinase (ILK) is a widely expressed serine/threonine-protein kinase that has been implicated in cancer development, progression, and metastasis. Yes-associated protein (YAP), as the most important effector of Hippo signaling pathway, which is considered to be a tumor suppressor pathway, acts as an oncogene in a variety of human cancers. The present study aimed to explore the expression of ILK and YAP1, the relationship between them, and the effect of ILK, YAP1 on prognosis in gliomas. Immunohistochemistry was used to examine the expression of ILK and YAP1. The χ2 test analyzes the relationship between ILK, YAP1, and pathologic parameters. The Spearman correlation analyzes the relationship between ILK and YAP1. Survival analysis was used to investigate the effect of ILK and YAP1 on prognosis. High expression of ILK was associated with the age above 50 (P=0.003), higher World Health Organization (WHO) grade (P0.001), recurrence (P0.001), and Ki-67 expression≥10% (P0.001). High expression of YAP1 was associated with higher WHO grade (P0.001), recurrence (P=0.043), and Ki-67 expression ≥10% (P=0.037). In lower grade gliomas, the high expression rate of ILK in isocitrate dehydrogenase 1 wild-type was higher than that in isocitrate dehydrogenase 1 mutant (P=0.048). The high expression rate of YAP1 in 1p19q non-codeletion was higher than that in 1p19q codeletion (P=0.022). There was a positive correlation between ILK and YAP1 (r=0.344). The patients with high expression of ILK and YAP1 had worse OS and PFS. As an upstream factor of the Hippo signaling pathway, ILK may affect the development and prognosis of gliomas by regulating YAP1.

The aroma characteristics of Pu-erh tea were studied in this work. A total of 117 volatile compounds were identified by HS-SPME combined with GC–TOF/MS, of which 29 active aroma compounds were identified by olfactometry. The active aroma compounds of Pu-erh tea were analyzed by intensity aroma (IA), aroma extraction dilution (AEDA), sensory quantification value (MF), detection frequency (DFA) and odor activity value (OAV). 24, 21 and 23 active aroma components were identified by DFA, AEDA and OAV, while 20 by IA and MF. Recombination of the obtained active aroma components indicated that OAV method was best for determining the active aroma compounds as the aroma profile of OAV recombination model was the most similar to that of Pu-erh tea sample. Omission test of the OAV recombination model furtherly identified 19 characteristic active aroma compounds of Pu-erh tea, and linalool, 1,2,3-trimenthoxybenzebe, 1,2,4-trimethoxybenzene and ɑ-ionone were the key characteristic active aromatic compounds.

Spindle and kinetochore associated (SKA) complex subunit, which maintains the stability of mitotic metaphase, with emerging research implying its effect as a carcinogenic regulator in cancer. However, its potential role in BC has not been fully elucidated. ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, cBioPortal and TIMER databases were performed to analyze the expression, prognosis, mutation, immune infiltration and potential biological mechanisms of SKA1/2/3 in BC. Our results showed that SKA1/2/3 expression was upregulated in BC. Survival analysis reveals that SKA3 overexpression was associated with poor overall survival (OS), relapse-free survival (RFS), post-progression survival (PPS) and distant metastasis-free survival (DMFS). SKA1 overexpression was associated with poor OS, RFS and DMFS while SKA2 overexpression was only associated with RFS and DMFS. Notably, the results implied that SKA1 has a good prognostic value in HER2-positive BC. Besides, the genetic alterations of SKA were investigated and the altered group correlated with shorter progress-free survival (PFS) and disease-specific survival (DSS). GO and KEGG analysis showed that SKA1/2/3 were implicated in regulating cell cycle, p53 signaling pathway and DNA replication. The 10 Hub genes in the protein network were upregulated in BC and related to poorer prognosis. Additionally, SKA1/2/3 expression was negatively correlated with infiltration of various immune cells with antitumor effects, whereas positively correlated with the expression of immune checkpoints molecules. Further experiments revealed that SKA1/2/3 silencing markedly impeded the proliferation and migration of BC cells. Herein, our study firmly shows that SKA genes may serve as a promising therapeutic target for patients with BC.

The timing of cytokinesis relative to other mitotic events in the fission yeast Schizosaccharomyces pombe is controlled by the septation initiation network (SIN). During a mitotic checkpoint, the SIN is inhibited by the E3 ubiquitin ligase Dma1 to prevent chromosome mis-segregation. Dma1 dynamically localizes to spindle pole bodies (SPBs) and the contractile ring (CR) during mitosis though its role at the CR is unknown. Here, we examined whether Dma1 phosphorylation affects its localization or function. We found that preventing Dma1 phosphorylation by substituting the six phosphosites with alanines diminished Dma1 CR localization but did not affect its mitotic checkpoint function. These studies reinforce the conclusion that Dma1 localization to the SPB is key to its role in the mitotic checkpoint.

Objective To perform a meta-analysis that investigates the prevalence and seroprevalence of celiac disease (CD) in Chinese general population and high-risk populations, and to summarize data from a serological survey of high-risk populations in Guangdong, China. Methods We collected data from the serological survey of high-risk populations in Guangdong, China (n = 1390) by testing serum tissue transglutaminase immunoglobulin A (tTG-IgA), deamidated gliadin peptides immunoglobulin A (DGP-IgA) and deamidated gliadin peptides immunoglobulin G (DGP-IgG), and also searched Medline, PubMed, Embase, Cochrane and 3 Chinese databases up to December 20, 2020 to estimate the pooled prevalence and seroprevalence of CD in China. Results In the serological survey, 0.94% (13/1390) individuals were positive for CD antibodies. In a meta-analysis of 18 studies, the seroprevalence of CD in Chinese general population was 0.27% (95% CI, 0.02-0.71). The seroprevalence of CD in Chinese high-risk populations was 8.34% (95% CI, 4.90-12.54), significantly higher than that in general population (OR 7.27, 95% CI, 4.06-13.04). The prevalence of biopsied-proven CD in high-risk Chinese populations was 4.44% (95% CI, 1.53-8.58). The seroprevalence of CD was varying with geographic origin, higher in Northern China than that in Southern China. Conclusions The basis for diagnosis of CD in Chinese patients should be through early case-finding by serological screening in high-risk groups; generous serological testing in patients with vague symptoms, especially in Northern Chinese.

Heterosis refers to the superior phenotypes observed in hybrids. Cytoplasmic male sterility (CMS) system plays an important role in cotton heterosis utilization. However, the global gene expression patterns of CMS-D2 and its interaction with the restorer gene Rf1 remain unclear. Here, the full-length transcript sequencing was performed in anthers of the CMS-D2 restorer line using PacBio single-molecule real-time sequencing technology. Combining PacBio SMRT long-read isoforms and Illumina RNA-seq data, 107,066 isoforms from 44,338 loci were obtained, including 10,086 novel isoforms of novel genes and 66,419 new isoforms of known genes. Totally 56,572 alternative splicing (AS) events, 1146 lncRNAs, 61 fusion transcripts and 10,466 genes exhibited alternative polyadenylation (APA), and 60,995 novel isoforms with predicted open reading frames (ORFs) were further identified. Furthermore, the specifically expressed genes in restorer line were selected and confirmed by qRT-PCR. These findings provide a basis for upland cotton genome annotation and transcriptome research, and will help to reveal the molecular mechanism of interaction between Rf1 and CMS-D2 cytoplasm.

Nitric oxide (NO)—the product of arginine metabolism catalyzed by nitric oxide synthases (NOS)—is a well-known neurotransmitter which plays an important role in metabolism and amino acid transportation in the nervous system. In particular, it can inhibit monoamine neurotransmitter transportation which affects animal behavior, especially social behavior. Shoaling—is a one kind of social behavior. It is a behavior that individual fish choose to join with their group within two factors; food and predation risk. Shoaling fish has quickly responded to predator and increased the change in feeding competition. In addition, shoaling also effect to stress response on stock density of aquaculture system. The effect of NO molecular signaling on the dopamine pathway was investigated using zebrafish (Danio rerio) as a model organism. Our aim was to understand the role of NOS and NO in shoaling behavior, which is typical of zebrafish. The concentration of NO in the zebrafish brain was modulated using a knockout for the neuronal NOS gene, and NO production was induced through treatment with L-arginine. The existence of NO in the zebrafish brain was confirmed by using a fluorescent probe. Dopamine concentration in the brain was measured by UPLC tandem mass spectrometer. We measured shoaling cohesion of all individual fish of D. rerio, using average distance between all pairs of fish (nearest neighbor distance) and analyzed tracking by Zebralab ViewPoint software. Collectively, our results suggest that a lower level of NO was associated with a higher level of dopamine, which in turn leads to the shoaling behavior.

Summary We propose a new concept that human somatic cells can be converted to become male germline stem cells by the defined factors. Here, we demonstrated that the overexpression of DAZL, DAZ2, and BOULE could directly reprogram human Sertoli cells into cells with the characteristics of human spermatogonial stem cells (SSCs), as shown by their similar transcriptomes and proteomics with human SSCs. Significantly, human SSCs derived from human Sertoli cells colonized and proliferated in vivo, and they could differentiate into spermatocytes and haploid spermatids in vitro. Human Sertoli cell-derived SSCs excluded Y chromosome microdeletions and assumed normal chromosomes. Collectively, human somatic cells could be converted directly to human SSCs with the self-renewal and differentiation potentials and high safety. This study is of unusual significance, because it provides an effective approach for reprogramming human somatic cells into male germ cells and offers invaluable male gametes for treating male infertility., Highlights • Human Sertoli cells can be converted into SSCs by overexpressing DAZ family genes • Human Sertoli cell-derived cells have phenotypic features with SSCs in vivo • Human Sertoli cell-derived SSCs differentiate into haploid spermatids in vitro • Human Sertoli cell-derived SSCs have normal chromosomes and no gene microdeletion, In this article, Zuping He and colleagues show that human Sertoli cells can be converted directly into human spermatogonial stem cells that are able to self-renew in vivo and differentiate into spermatocytes and haploid spermatids in vitro via the overexpression of three DAZ family genes.

Genes related to human longevity have not been studied so far, and need to be investigated thoroughly. This study aims to explore the relationship among ABO gene variants, lipid levels, and longevity phenotype in individuals (≥90yrs old) without adverse outcomes. A genotype-phenotype study was performed based on 5803 longevity subjects and 7026 younger controls from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Four ABO gene variants associated with healthy longevity (rs8176719 C, rs687621 G, rs643434 A, and rs505922 C) were identified and replicated in the CLHLS GWAS data analysis and found significantly higher in longevity individuals than controls. The Bonferroni adjusted p-value and OR range were 0.013-0.020 and 1.126-1.151, respectively. According to the results of linkage disequilibrium (LD) analysis, the above four variants formed a block on the ABO gene (D'=1, r2range = 0.585-0.995). The carriers with genotypes rs687621 GG, rs643434 AX, or rs505922 CX (prange = 2.728 x 10-107-5.940 x 10-14; ORrange = 1.004-4.354) and haplotype CGAC/XGXX (p = 2.557 x 10-27; OR = 2.255) had a substantial connection with longevity, according to the results of genetic model analysis. Following the genotype and metabolic phenotype analysis, it has been shown that the longevity individuals with rs687621 GG, rs643434 AX, and rs505922 CX had a positive association with HDL-c, LDL-c, TC, TG (prange = 2.200 x 10-5-0.036, ORrange = 1.546-1.709), and BMI normal level (prange = 2.690 x 10-4-0.026, ORrange = 1.530-1.997). Finally, two pathways involving vWF/ADAMTS13 and the inflammatory markers (sE-selectin/ICAM1) that co-regulated lipid levels by glycosylation and effects on each other were speculated. In conclusion, the association between the identified longevity-associated ABO variants and better health lipid profile was elucidated, thus the findings can help in maintaining normal lipid metabolic phenotypes in the longevity population.

Wei Zhang,1,2 Zhirong Li,3 Na Wang,1 Zhicong Yang,1 Jia Li,1 Caiqing Li,1 Xuying Han,1 Jinlu Liu,1 Liping Li,4 Shuwang Wang,4 Minghua Zhan1,5 1Microbiology Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei Province, People’s Republic of China; 2Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 3Clinical Laboratory, Hebei Provincial Center for Clinical Laboratories, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Clinical Laboratory, Zhangjiakou Xuan Gang Hospital, Zhangjiakou, Hebei Province, People’s Republic of China; 5Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Minghua ZhanDepartment of Clinical Laboratory, The First Affiliated Hospital of Hebei North University and Peking University People’s Hospital, No. 11 South Street, Xi Zhi Men, Beijing, 100044, People’s Republic of ChinaTel +86-15531311750Fax +86-1088326317Email minghuazhan02@163.comPurpose: To explore the clinical distribution characteristics and antimicrobial susceptibilities of carbapenem-resistant Escherichia coli (CR-ECO) in Hebei Province, China, from 2017 to 2019, and provide data on the treatment of this bacterial infection and the prevention of its spread.Materials and Methods: A total of 1439 CR-ECO strains were collected from 2017 to 2019 in Hebei Province, China. Drug sensitivity tests were performed using the minimum inhibitory concentration (MIC) method, and the data were analyzed statistically using WHONET5.6 software.Results: A total of 54,377 strains of Escherichia coli were isolated in Hebei Province from 2017 to 2019, of which 1439 strains were CR-ECO (2.65%). The highest proportion (33.78%) of strains was isolated from urine, and the detection rate showed a slow downward trend over the past 3 years. CR-ECO was mainly detected in densely populated and economically developed areas. Of all the patients, 54.2% were from the medical ward; the ratio of male to female patients with CR-ECO infections was 1.35:1; elderly patients and adults accounted for 59.6% and 30.8%, respectively, whereas minors and newborns accounted for 4.9% and 4.7%, respectively. For CR-ECO, the drug resistance rates to β-lactams were all higher than 80% and there was an annual increasing trend, while the drug resistance rates to quinolones remained nearly unchanged. The rate of resistance to aminoglycosides was relatively low, especially to amikacin (approximately 22%). The MIC50 of other antibacterial drugs, except amikacin, was equal to or higher than the break point of drug resistance.Conclusion: From 2017 to 2019, the isolation rate of CR-ECO in Hebei Province, China, remained stable; however, the drug resistance rate showed an upward trend, primarily in cases of urinary tract infections in older men; the resistance rate to amikacin was the lowest.Keywords: Enterobacteriales bacteria, multidrug resistance, MIC50/MIC90, regional distribution