The elite eating quality alleles Wxb and ALKb are regulated by OsDOF18 and coordinately improve head rice yield.

Head rice yield (HRY) measures rice milling quality and determines final grain yield and commercial value. Here, we report that two major quantitative trait loci for milling quality in rice, qMq-1 and qMq-2, represent allelic variants of Waxylv/Waxyb (hereafter Wx) encoding Granule-Bound Starch Synthase I (GBSSI) and Alkali Spreading Value ALKc/ALKb encoding Soluble Starch Synthase IIa (SSIIa), respectively. Complementation and overexpression transgenic lines in indica and japonica backgrounds confirmed that Wx and ALK coordinately regulate HRY by affecting amylose content, the number of amylopectin branches, amyloplast size, and thus grain filling and hardness. The transcription factor OsDOF18 acts upstream of Wx and ALK by activating their transcription. Furthermore, rice accessions with Wxb and ALKb alleles showed improved HRY over those with Wxlv and ALKc. Our study not only reveals the novel molecular mechanism underlying the formation of HRY but also provides a strategy for breeding rice cultivars with improved HRY.

Genome-wide characterization of the TGF-ß gene family and their expression in different tissues during tail regeneration in the Schlegel's Japanese gecko Gekko japonicus.

The transforming growth factor-ß (TGF-ß) gene family is unique to animals and is involved in various important processes including tissue regeneration. Here, we identified 52 TGF-ß family genes based on genome sequences of the gecko (Gekko japonicus), compared TGF-ß genes between G. japonicus and other four reptilian species, and evaluated the expression of 14 randomly selected genes in muscle, kidney, liver, heart, and brain during tail regeneration to investigate whether their expression was tissue-dependent. We detected 23 conserved domains, 13 in the TGF-ß ligand subfamily, and 10 in the receptor subfamily. The pattern of higher genetic variation in the ligand subfamily than in the receptor subfamily in vertebrates might result from the precise localization of agonists and antagonists in the cell surface and intracellular compartment. TGF-ß genes were unevenly distributed across 15 chromosomes in G. japonicus, presumably resulting from gene losses and gains during evolution. Genes in the TGF-ß receptor subfamily (ACVR2A, ACVR2B, ACVR1, BMPR1A, ACVRL1, BMPR2 and TGFBR1) played a vital role in the TGF-ß signal pathway. The expression of all 14 randomly selected TGF-ß genes was tissue-specific. Our study supports the speculation that some TGF-ß family genes are involved in the early stages of tail regeneration.

Dexamethasone Induces Senescence-Associated Changes in Trabecular Meshwork Cells by Increasing ROS Levels Via the TGFß/Smad3-NOX4 Axis.

Glaucoma is a serious complication of glucocorticoid (GC) therapy arising through elevations in intraocular pressure (IOP). Dexamethasone (DEX) is reported to contribute to elevated IOP through different effects on the trabecular meshwork but whether DEX contributes to glaucoma development through the induction of cellular senescence is still unclear. We explored the actions of DEX on transformed human trabecular meshwork cells (HTMCs) using RNA-seq and conducted bioinformatic analyses to determine the affected pathways. Among the 4,103 differentially expressed genes identified in transformed HTMCs treated with 400 nM DEX (2,036 upregulated and 2,067 downregulated genes, respectively), bioinformatic analyses revealed significant enrichment and potential interplay between the transforming growth factor beta (TGFß)41; signaling and cellular senescence pathways. DEX treatment induced senescence changes in primary and transformed HTMCs as indicated by increases in SA-ß-gal positivity, interleukin (IL)-6 secretion, and senescence-associated heterochromatin foci (SAHF) along with selective accumulation of senescence marker p15 and elevations in reactive oxygen species (ROS) levels. Notably, the DEX-induced senescence changes were rescued by treatment with the TGFß/Smad3 pathway inhibitor SIS3. Furthermore, we show that DEX increases cellular ROS levels via upregulation of NADPH oxidase 4 (NOX4) through activation of Smad3, and that SIS3 decreases ROS levels by downregulating NOX4. Instructively, inhibiting NOX4 with GLX351322 and scavenging ROS with NAC were both effective in preventing DEX-induced senescence changes. Similarly, we found in the mouse model that DEX-ac upregulated p15 and NOX4 expression in the trabecular meshwork, with cotreatment with GLX351322 alleviating elevations in IOP. We establish that DEX induces senescence changes in HTMCs by increasing ROS levels via the TGFß/Smad3/NOX4 axis, increasing IOP and contributing to glaucoma development.

Genomic insights into local adaptation in the Asiatic toad Bufo gargarizans, and its genomic offset to climate warming.

Genomic signatures of local adaptation have been identified in many species but remain sparsely studied in amphibians. Here, we explored genome-wide divergence within the Asiatic toad, Bufo gargarizans, to study local adaptation and genomic offset (i.e., the mismatch between current and future genotype-environment relationships) under climate warming scenarios. We obtained high-quality SNP data for 94 Asiatic toads from 21 populations in China to study spatial patterns of genomic variation, local adaptation, and genomic offset to warming in this wide-ranging species. Population structure and genetic diversity analysis based on high-quality SNPs revealed three clusters of B. gargarizans in the western, central-eastern, and northeastern portions of the species' range in China. Populations generally dispersed along two migration routes, one from the west to the central-east and one from the central-east to the northeast. Both genetic diversity and pairwise F ST were climatically correlated, and pairwise F ST was also correlated with geographic distance. Spatial genomic patterns in B. gargarizans were determined by the local environment and geographic distance. Global warming will increase the extirpation risk of B. gargarizans.

Elevated Angiotensin-II Levels Contribute to the Pathogenesis of Open-Angle Glaucoma Via Inducing the Expression of Fibrosis-Related Genes in Trabecular Meshwork Cells Through a ROS/NOX4/SMAD3 Axis.

Glaucoma including primary open-angle glaucoma (POAG) results from elevations in intraocular pressure (IOP). An eye-localized renin-angiotensin system (RAS) has been implicated in IOP regulation, although its mechanism of action and contribution to glaucoma is poorly understood. Here, we detected significant increases in the levels of angiotensin II (ANGII) in aqueous humor samples from POAG patients. Moreover, we determined that the concentrations of ANGII were positively correlated with IOP, suggesting a role for elevated ANGII levels in eye pathogenesis. Functional investigations demonstrated that ANGII induces the expression of fibrosis-related genes of transformed and primary human trabecular meshwork cells (HTMCs) through the transcriptional upregulation of key fibrotic genes. Parallel experiments using a murine periocular conjunctival fornix injection model confirmed that ANGII induces the expression of fibrosis-related genes in trabecular meshwork (TM) cells in vivo along with increasing IOP. ANGII was revealed to function through increasing the levels of reactive oxygen species (ROS) via selectively upregulating NOX4, with NOX4 knockdown or inhibition with GLX351322 alleviating fibrotic changes induced by ANGII. We further show that ANGII activates Smad3, with both GLX351322 and an inhibitor of Smad3 (SIS3) decreasing the phosphorylation of Smad3 and dampening the ANGII-induced increases in fibrotic proteins. Moreover, NOX4 and Smad3 inhibitors also partially rescued the elevated IOP levels induced by ANGII. Our collective results therefore highlight ANGII as a biomarker and treatment target in POAG together with establishing a causal relationship between ANGII and up-regulation of the expression of fibrosis-related genes of TM cells via a NOX4/ROS axis in cooperation with TGFß/Smad3 signaling.

Gut microbiota differs between two cold-climate lizards distributed in thermally different regions.

BACKGROUND: The metabolic cold-climate adaption hypothesis predicts that animals from cold environments have relatively high metabolic rates compared with their warm-climate counterparts. However, studies testing this hypothesis are sparse. Here, we compared gut microbes between two cold-climate lizard species of the genus Phrynocephalus to see if gut microbiota could help lizards adapt to cold environments by promoting metabolism. We conducted a 2 species (P. erythrurus and P. przewalskii) × 2 temperatures (24 and 30 °C) factorial design experiment, whereby we kept lizards of two Phrynocephalus species at 24 and 30 °C for 25 d and then collected their fecal samples to analyze and compare the microbiota based on 16S rRNA gene sequencing technology. RESULTS: The gut microbiota was mainly composed of bacteria of the phyla Proteobacteria, Firmicutes, Bacteroidetes, and Verrucomicrobia in both species (Proteobacteria > Firmicutes > Verrucomicrobiota in P. erythrurus, and Bacteroidetes > Proteobacteria > Firmicutes in P. przewalskii). Further analysis revealed that the gut microbiota promoted thermal adaptation in both lizard species, but with differences in the relative abundance of the contributory bacteria between the two species. An analysis based on the Kyoto Encyclopedia of Genes and Genomes revealed that the gut microbiota played important roles in metabolism, genetic information processing, cellular processes, and environmental information processing in both species. Furthermore, genes related to metabolism were more abundant in P. erythrurus at 24 °C than in other species ⋅ temperature combinations. CONCLUSION: Our study provides evidence that gut microbiota promotes thermal adaptation in both species but more evidently in P. erythrurus using colder habitats than P. przewalskii all year round, thus confirming the role of gut microbiota in cold-climate adaptation in lizards.

Quality assessment of clinical practice guidelines on psychological distress of cancer patients using the AGREE II instrument.

Objective: This study aimed to assess the quality of the clinical practice guidelines on psychological distress among cancer patients and provide users with recommendations for coping with psychological distress. Methods: A systematic search of relevant clinical practice guidelines was undertaken to identify and select the clinical practice guidelines related to psychological distress among cancer patients. Literature databases were searched in PubMed, Web of Science, Excerpta Medica Database, the Cumulative Index to Nursing & Allied Health Literature, China Biology Medicine, China National Knowledge Infrastructure, WanFang and Weipu Journal Database. The guideline databases include Yimaitong Guidelines Network, National Guideline Clearinghouse, National Institute for Health and Clinical Excellence, American Society of Clinical Oncology (ASCO), New Zealand Guidelines Group, Scottish Intercollegiate GuidelinesNetwork, American Psychological Association, Registered Nurses' Association of Ontario and Cancer Care Ontario (CCO). Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Results: Six clinical practice guidelines were included and assessed for critical evaluation. The median score for the scope and purpose domain was 71.5% (IQR 64%-77.25%), the stakeholder involvement domain was 65% (IQR 47.5%-74.5%), the rigour of the development domain was 61.5% (IQR 45.5%-85.25%), the clarity of the presentation domain was 91% (IQR 72.25%-94.5%), the applicability domain was 70% (IQR 33%-78.75%), and the editorial independence domain was 48.84% (IQR 61.75%-95%). Four guidelines (ASCO, 2014; Canadian Association of Psychosocial Oncology, 2015; NCCN, 2020, and CCO, 2016) were classified as "recommended," and the remaining (European Palliative Care Research Collaborative and Chinese Psychosocial Oncology Society) were "recommended with modifications," especially in the domains of Stakeholder involvement, rigour of development, and applicability. The inter-rater consistency of each domain showed moderate level (0.52-0.90) analyzing by intraclass correlation. Conclusions: The clinical practice guidelines on psychological distress among cancer patients varied in quality, and there were discrepancies in terms of the recommendations and recommendation grades. These findings could contribute to improving the quality of clinical practice guidelines on psychological distress, and enable the development and implementation of evidence-based guidelines for cancer patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42020209204.

Loss and Natural Variations of Blast Fungal Avirulence Genes Breakdown Rice Resistance Genes in the Sichuan Basin of China.

Magnaporthe oryzae is the causative agent of rice blast, a devastating disease in rice worldwide. Based on the gene-for-gene paradigm, resistance (R) proteins can recognize their cognate avirulence (AVR) effectors to activate effector-triggered immunity. AVR genes have been demonstrated to evolve rapidly, leading to breakdown of the cognate resistance genes. Therefore, understanding the variation of AVR genes is essential to the deployment of resistant cultivars harboring the cognate R genes. In this study, we analyzed the nucleotide sequence polymorphisms of eight known AVR genes, namely, AVR-Pita1, AVR-Pii, AVR-Pia, AVR-Pik, AVR-Pizt, AVR-Pi9, AVR-Pib, and AVR-Pi54 in a total of 383 isolates from 13 prefectures in the Sichuan Basin. We detected the presence of AVR-Pik, AVR-Pi54, AVR-Pizt, AVR-Pi9, and AVR-Pib in the isolates of all the prefectures, but not AVR-Pita1, AVR-Pii, and AVR-Pia in at least seven prefectures, indicating loss of the three AVRs. We also detected insertions of Pot3, Mg-SINE, and indels in AVR-Pib, solo-LTR of Inago2 in AVR-Pizt, and gene duplications in AVR-Pik. Consistently, the isolates that did not harboring AVR-Pia were virulent to IRBLa-A, the monogenic line containing Pia, and the isolates with variants of AVR-Pib and AVR-Pizt were virulent to IRBLb-B and IRBLzt-t, the monogenic lines harboring Pib and Piz-t, respectively, indicating breakdown of resistance by the loss and variations of the avirulence genes. Therefore, the use of blast resistance genes should be alarmed by the loss and nature variations of avirulence genes in the blast fungal population in the Sichuan Basin.

Rapid ultrasensitive detection of hexavalent chromium in soil and groundwater by a microProbing imaging platform.

Rapid detection methods are needed to investigate the environmental quality risk of soil and groundwater in contaminated lands. Currently there is lack of rapid detection methods to sensitively and accurately analyze contaminations of hexavalent chromium in soil due to the challenge of complex sample pretreatment or expensive instrumentation. Here we report a rapid accurate detection platform for quantifying hexavalent chromium in soil and groundwater with ultrasensitivity. The platform consists of a novel sensor of microProbing beads and a portable microscope. Each microProbing bead was a nanoliter reactor to selectively sequestrate Cr (VI) with the enrichment factor up to 150 ×. The microProbing beads presented the signal uniformity of ~97% for the statistical colorimetric imaging analysis. Combined with a miniaturized microscope, the microProbing beads allowed for detecting aqueous Cr (VI) and soluble Cr (VI) in soil within 45 min. The platform achieved high sensitivity with the detection limits of 0.003 ppb for aqueous Cr (VI) and 0.07 ppm for soil Cr (VI). It accurately detected soil and groundwater samples from a chromium contaminated land in Yangtze River Basin of China. The consistency to the laboratory standard methods was achieved with the low cost of ~0.20 US dollar per test. The microProbing imaging platform with the operational simplicity and device portability is highly promising for the field analysis of Cr (VI) in contaminated lands.

The Diagnostic Value of Serum Exosomal Has_circ_0000615 for Breast Cancer Patients.

BACKGROUND: To explore the expression level of has_circ_0000615 in peripheral blood samples and evaluate its diagnostic value for breast cancer patients. METHODS: The peripheral blood samples of 95 breast cancer patients who underwent curative surgical resection and 95 age-matched healthy volunteers in our institutions from September 2019 to November 2020 were systematically collected. The expression level of has_circ_0000615 in the plasma was amplified and detected by qRT-PCR, and its correlation to clinicopathological characteristics of breast cancer patients were analyzed. RESULTS: Breast cancer patients had a significantly higher expression level of has_circ_0000615 in the plasma than healthy controls (P < 0.01), and its high expression was closely associated with advanced tumor stage (P=0.010), lymph node metastasis (P = 0.001) and high grade of recurrence risk (P=0.012). The receiver operator characteristic (ROC) curves showed that the area under curve (AUC) value, sensitivity and specificity of has_circ_0000615 for the diagnosis of non-metastatic breast cancer was 0.904 (95% CI: 0.863-0.944), 76.8% and 88.4%, respectively. Serum has_circ_0000615 expression had a better diagnostic efficiency than routine tumor biomarkers such as CA153, CA125 and CEA for distinguishing breast cancer patients from healthy individuals. TEM revealed that isolated exosomes from the culture medium of breast cancer cells had a disk-like appearance with a diameter of 80-200 nm vesicles, and the expression of exosome markers CD9 and CD81 was markedly increased. More importantly, the expression of has_circ_0000615 was detected in the exosomes and its expression level was markedly upregulated in breast cancer cell lines compared with normal ductal epithelial cells. The stability assay showed that there was no difference between RNA extraction at 0 hour and 24 hours in terms of the expression of has_circ_0000615 (P =0.327). Has_circ_0000615 might as exosomes be secreted into the circulating blood of breast cancer patients, resulting in a high expression level in plasma samples. CONCLUSION: The detection of has_circ_0000615 might be a promising diagnostic method for breast cancer.

VS2nanosheet as a promising candidate of recycle and reuse NO2gas sensor and capturer: a DFT study.

We describe the utilization of VS2nanosheet as high sensing response, reuse, and thermodynamic stability at room temperature NO2and NO gas sensors by using the density functional theory method. We focus on the electronic structures and adsorption energy toward a variety of gaseous molecules (such as O2, CO, H2O, NH3, NO, and NO2) adsorbed on the VS2nanosheet. The results show that chemical interactions existed between NO/NO2molecules and VS2nanosheet due to sizable adsorption energy and strong covalent (S-N) bonds. In particular, the adsorption energies, charge transfer and electronic properties between NO2adsorbed system is significantly changed compared with the other gas molecules (CO, NO, H2O, NH3, and O2) adsorbed systems under biaxial strains, which is effective to achieve the capture or reversible release of NO2for cycling capability. Our analysis indicates that VS2nanosheet is promising as electrical devices candidate for NO2high-performance gas sensor or capturer.

Modulation of the electronic properties and spin polarization of 2H VS2 nanoribbons by tuning ribbon widths and edge decoration.

The band structures and spin-polarization characteristics of armchair and zigzag VS2 nanoribbons with different terminated edges are investigated based on density functional theory (DFT) calculations with a spin polarized meta-GGA. The results reveal that zigzag 2H VS2 nanoribbons exhibit metal, half-metal, or semiconductor electrical characteristics with different edge decorations or ribbon widths. And the spin polarized ratio can achieve 100% self-polarization for the zigzag VS2 nanoribbons with V atom edges. The Curie temperatures (TC) estimated by mean field approximation simulations for the zigzag 2H VS2 nanoribbons with terminated edges of V systems are 276 K. These preliminary findings offer an effective treatment option for controllable and adjustable spintronic devices.

Stability and Repeatability of a Karst-like Hierarchical Porous Silicon Oxide-Based Memristor.

A memristor architecture based on porous oxide materials has the potential to be used in artificial synaptic devices. Herein, we present a memristor system employing a karst-like hierarchically porous (KLHP) silicon oxide structure with good stability and repeatability. The KLHP structure prepared by an electrochemical process and thermal oxidation exhibits high ON-OFF ratios up to 105 during the endurance test, and the data can be maintained for 105 s at a small read voltage 0.1 V. The mechanism of lithium ion migration in the porous silicon oxide structure has been discussed by a simulated model. The porous silicon oxide-based memristor is very promising because of the enhanced performance as well as easily accessed neuromorphic computing.

A theoretical simulation of small-molecules sensing on an S-vacancy SnS2 monolayer.

Using first-principle atomistic simulations, we focused on the electronic structures of small gas molecules (CO, H2O, NH3, NO, and NO2) adsorbed on the S-vacancy SnS2 monolayer. The results show that H2O and CO molecules were physisorbed on the S-vacancy SnS2 monolayer, whereas NH3, NO, and NO2 molecules were chemisorbed on the S-vacancy SnS2 monolayer via strong covalent bonds. Moreover, our calculations show that H2O and NH3 act as charge donors, whereas CO, NO, and NO2 gas molecules act as acceptors. Different adsorption behaviors of common gas molecules on the S-vacancy SnS2 monolayer provide a feasible way to exploit chemical gas sensors and electrical devices. In particular, our results also show that under applied biaxial strains, the adsorption energy and charge transfer of gas molecules on the S-vacancy SnS2 monolayer dramatically changed, which indicates that external factors on the S-vacancy SnS2 monolayer are highly preferred.