Upland rice genomic signatures of adaptation to drought resistance and navigation to molecular design breeding.

Upland rice is a distinctive drought-aerobic ecotype of cultivated rice highly resistant to drought stress. However, the genetic and genomic basis for the drought-aerobic adaptation of upland rice remains largely unclear due to the lack of genomic resources. In this study, we identified 25 typical upland rice accessions and assembled a high-quality genome of one of the typical upland rice varieties, IRAT109, comprising 384 Mb with a contig N50 of 19.6 Mb. Phylogenetic analysis revealed upland and lowland rice have distinct ecotype differentiation within the japonica subgroup. Comparative genomic analyses revealed that adaptive differentiation of lowland and upland rice is likely attributable to the natural variation of many genes in promoter regions, formation of specific genes in upland rice, and expansion of gene families. We revealed differentiated gene expression patterns in the leaves and roots of the two ecotypes and found that lignin synthesis mediated by the phenylpropane pathway plays an important role in the adaptive differentiation of upland and lowland rice. We identified 28 selective sweeps that occurred during domestication and validated that the qRT9 gene in selective regions can positively regulate drought resistance in rice. Eighty key genes closely associated with drought resistance were appraised for their appreciable potential in drought resistance breeding. Our study enhances the understanding of the adaptation of upland rice and provides a genome navigation map of drought resistance breeding, which will facilitate the breeding of drought-resistant rice and the "blue revolution" in agriculture.

Syringic acid promotes cartilage extracellular matrix generation and attenuates osteoarthritic cartilage degradation by activating TGF-ß/Smad and inhibiting NF-κB signaling pathway.

Osteoarthritis (OA) is a common chronic degenerative disease which is characterized by the disruption of articular cartilage. Syringic acid (SA) is a phenolic compound with anti-inflammatory, antioxidant, and other effects including promoting osteogenesis. However, the effect of SA on OA has not yet been reported. Therefore, the purpose of our study was to investigate the effect and mechanism of SA on OA in a mouse model of medial meniscal destabilization. The expressions of genes were evaluated by qPCR or western blot or immunofluorescence. RNA-seq analysis was performed to examine gene transcription alterations in chondrocytes treated with SA. The effect of SA on OA was evaluated using destabilization of the medial meniscus model of mice. We found that SA had no obvious toxic effect on chondrocytes, while promoting the expressions of chondrogenesis-related marker genes. The results of RNA-seq analysis showed that extracellular matrix-receptor interaction and transforming growth factor-ß (TGF-ß) signaling pathways were enriched among the up-regulated genes by SA. Mechanistically, we demonstrated that SA transcriptionally activated Smad3. In addition, we found that SA inhibited the overproduction of lipopolysaccharide-induced inflammation-related cytokines including tumor necrosis factor-α and interleukin-1ß, as well as matrix metalloproteinase 3 and matrix metalloproteinase 13. The cell apoptosis and nuclear factor-kappa B (NF-κB) signaling were also inhibited by SA treatment. Most importantly, SA attenuated cartilage degradation in a mouse OA model. Taken together, our study demonstrated that SA could alleviate cartilage degradation in OA by activating the TGF-ß/Smad and inhibiting NF-κB signaling pathway.

Type I/type III IFN and related factors regulate JEV infection and BBB endothelial integrity.

BACKGROUND: Japanese encephalitis virus (JEV) remains a predominant cause of Japanese encephalitis (JE) globally. Its infection is usually accompanied by disrupted blood‒brain barrier (BBB) integrity and central nervous system (CNS) inflammation in a poorly understood pathogenesis. Productive JEV infection in brain microvascular endothelial cells (BMECs) is considered the initial event of the virus in penetrating the BBB. Type I/III IFN and related factors have been described as negative regulators in CNS inflammation, whereas their role in JE remains ambiguous. METHODS: RNA-sequencing profiling (RNA-seq), real-time quantitative PCR, enzyme-linked immunosorbent assay, and Western blotting analysis were performed to analyze the gene and protein expression changes between mock- and JEV-infected hBMECs. Bioinformatic tools were used to cluster altered signaling pathway members during JEV infection. The shRNA-mediated immune factor-knockdown hBMECs and the in vitro transwell BBB model were utilized to explore the interrelation between immune factors, as well as between immune factors and BBB endothelial integrity. RESULTS: RNA-Seq data of JEV-infected hBMECs identified 417, 1256, and 2748 differentially expressed genes (DEGs) at 12, 36, and 72 h post-infection (hpi), respectively. The altered genes clustered into distinct pathways in gene ontology (GO) terms and KEGG pathway enrichment analysis, including host antiviral immune defense and endothelial cell leakage. Further investigation revealed that pattern-recognition receptors (PRRs, including TLR3, RIG-I, and MDA5) sensed JEV and initiated IRF/IFN signaling. IFNs triggered the expression of interferon-induced proteins with tetratricopeptide repeats (IFITs) via the JAK/STAT pathway. Distinct PRRs exert different functions in barrier homeostasis, while treatment with IFN (IFN-ß and IFN-λ1) in hBMECs stabilizes the endothelial barrier by alleviating exogenous destruction. Despite the complex interrelationship, IFITs are considered nonessential in the IFN-mediated maintenance of hBMEC barrier integrity. CONCLUSIONS: This research provided the first comprehensive description of the molecular mechanisms of host‒pathogen interplay in hBMECs responding to JEV invasion, in which type I/III IFN and related factors strongly correlated with regulating the hBMEC barrier and restricting JEV infection. This might help with developing an attractive therapeutic strategy in JE.

RRS1 shapes robust root system to enhance drought resistance in rice.

A strong root system facilitates the absorption of water and nutrients from the soil, to improve the growth of crops. However, to date, there are still very few root development regulatory genes that can be used in crop breeding for agriculture. In this study, we cloned a negative regulator gene of root development, Robust Root System 1 (RRS1), which encodes an R2R3-type MYB family transcription factor. RRS1 knockout plants showed enhanced root growth, including longer root length, longer lateral root length, and larger lateral root density. RRS1 represses root development by directly activating the expression of OsIAA3 which is involved in the auxin signaling pathway. A natural variation in the coding region of RRS1 changes the transcriptional activity of its protein. RRS1T allele, originating from wild rice, possibly increases root length by means of weakening regulation of OsIAA3. Knockout of RRS1 enhances drought resistance by promoting water absorption and improving water use efficiency. This study provides a new gene resource for improving root systems and cultivating drought-resistant rice varieties with important values in agricultural applications.

Direct Alkylation of Quinoxalinones with Boracene-Based Alkylborate under Visible Light Irradiation.

An efficient synthesis of a variety of 3-alkyl quinoxalinones via C-H direct alkylation by photoredox catalysis between quinoxalinones and alkylborates is reported. A range of quinoxalinones was tolerated well. This visible-light photocatalysis reaction allows access to structurally diverse 3-alkyl quinoxalinones in good to excellent yields. The practicality of this protocol was demonstrated by the concise synthesis of a potential bioactive nonpeptide angiotensin II receptor antagonist.

Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis.

Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) in streptozotocin (STZ)-injected rats, but the mechanism remained largely unknown. Therefore, we further explored its possible mechanism. We subcutaneously injected 5 U hirudin into STZ-induced WT mice or Gasdermin D (Gsdmd)-/- (KO) mice daily for 12 weeks, respectively, and evaluated their kidney injury. Next, glomerular endothelial cells (GECs), renal tubular epithelial cells (RTECs), and bone-marrow-derived macrophages (BMDMs) were isolated from WT mice and treated with hirudin in the presence of high glucose/lipopolysaccharides and ATP to measure the release of interleukin-18 and interleukin-1ß. Kidney injury induced by STZ injection was significantly ameliorated by hirudin through inhibiting Gsdmd-mediated pyroptosis in the mice, not Caspase 1-mediated apoptosis. Meanwhile, hirudin also suppressed pyroptosis in primary GECs, RTECs, and BMDMs in vitro. Moreover, the deletion of Gsdmd reduced pyroptosis and kidney injury both in vivo and in vitro. We also found that hirudin regulated the expression of Gsdmd by inhibiting interferon regulatory factor 2 (Irf2). Hirudin ameliorated Gsdmd-mediated pyroptosis by inhibiting irf2, leading to the improvement of kidney injury. Therefore, hirudin might serve as a potential therapeutic strategy to treat DN.

Liquid Marbles under Electric Fields: New Capabilities for Non-wetting Droplet Manipulation and Beyond.

The study of liquid marbles (LMs) composed of stabilizing liquid droplets with solid particles in a gaseous environment has matured into an established area in surface and colloid science. The minimized "solid-liquid-air" triphase interface enables LMs to drastically reduce adhesion to a solid substrate, making them unique non-wetting droplets transportable with limited energy. The small volume, enclosed environment, and simple preparation render them suitable microreactors in industrial applications and processes such as cell culture, material synthesis, and blood coagulation. Extensive application contexts request precise and highly efficient manipulations of these non-wetting droplets. Many external fields, including magnetic, acoustic, photothermal, and pH, have emerged to prepare, deform, actuate, coalesce, mix, and disrupt these non-wetting droplets. Electric fields are rising among these external stimuli as an efficient source for manipulating the LMs with high controllability and a significant ability to contribute further to proposed applications. This Feature Article attempts to outline the recent developments related to LMs with the aid of electric fields. The effects of electric fields on the preparation and manipulation of LMs with intricate interfacial processes are discussed in detail. We highlight a wealth of novel electric field-involved LM-based applications and beyond while also envisaging the challenges, opportunities, and new directions for future development in this emerging research area.

Three-Dimensional Perovskite Nanopixels for Ultrahigh-Resolution Color Displays and Multilevel Anticounterfeiting.

Hybrid perovskites are emerging as a promising, high-performance luminescent material; however, the technological challenges associated with generating high-resolution, free-form perovskite structures remain unresolved, limiting innovation in optoelectronic devices. Here, we report nanoscale three-dimensional (3D) printing of colored perovskite pixels with programmed dimensions, placements, and emission characteristics. Notably, a meniscus comprising femtoliters of ink is used to guide a highly confined, out-of-plane crystallization process, which generates 3D red, green, and blue (RGB) perovskite nanopixels with ultrahigh integration density. We show that the 3D form of these nanopixels enhances their emission brightness without sacrificing their lateral resolution, thereby enabling the fabrication of high-resolution displays with improved brightness. Furthermore, 3D pixels can store and encode additional information into their vertical heights, providing multilevel security against counterfeiting. The proof-of-concept experiments demonstrate the potential of 3D printing to become a platform for the manufacture of smart, high-performance photonic devices without design restrictions.

Pseudomonas nanhaiensis sp. nov., a lipase-producing bacterium isolated from deep-sea sediment of the South China Sea.

A bacterial lipase producing bacterium, designated SCS 2-3, was isolated from deep-sea sediment of the South China Sea. Phylogenetic analysis based on the 16S rRNA sequence revealed that strain SCS2-3 belonged to the genus Pseudomonas and had 98.56% similarity to P. xinjiangensis NRRL B-51270T as the closest relative strain. MLSA using four protein-coding genes (dnaK, gyrA, recA, and rpoB) showed strain SCS 2-3 to form a separate branch. ANI and in silico DDH values between strain SCS 2-3 and related type strains of Pseudomonas were less than 81.51% and 23.80%, respectively. Genome comparison showed that strain SCS 2-3 shared 1875 core gene families with other eight closely related type strains in Pseudomonas, and the number of strain-unique genes was 263. Through gene annotations, genes related to lipase were found in the genome. Furthermore, a combination of phenotypic, chemotaxonomic, phylogenetic and genotypic data clearly indicated that strain SCS 2-3 represents a novel species of the genus Pseudomonas, for which the name Pseudomonas nanhaiensis sp. nov. is proposed. The type strain is SCS 2-3T (= GDMCC 1.2219T = JCM 34440T).

Porous g-C3N4 with defects for the efficient dye photodegradation under visible light.

Porous graphitic carbon nitride (p-C3N4) was fabricated via simple pyrolyzing treatment of graphitic carbon nitride (g-C3N4). The defects could be introduced into the structure of g-C3N4 by breakage of some bonds, which was beneficial for the generation of electron-hole pairs and inhibiting their recombination. Compared with g-C3N4, p-C3N4 showed a narrow band gap to promote the utilization of visible light. Furthermore, the porous structure also increased the specific surface area to maximize the exposure of active sites and promote mass transfer during photodegradation. As a result, the as-reported p-C3N4 exhibited considerably higher degradation efficiency for Rhodamine B (RhB) and Methyl Orange (MO) than that of the original g-C3N4. Moreover, the photocatalyst showed high durability and stability in recycling experiments.

Z-Selective α-Arylation of α,ß-Unsaturated Nitriles via [3,3]-Sigmatropic Rearrangement.

The Morita-Baylis-Hillman (MBH) reaction and [3, 3]-sigmatropic rearrangement are two paradigms in organic synthesis. We have merged the two types of reactions to achieve [3,3]-rearrangement of aryl sulfoxides with α,ß-unsaturated nitriles. The reaction was achieved by sequentially treating both coupling partners with electrophilic activator (Tf2 O) and base, offering an effective approach to prepare synthetically versatile α-aryl α,ß-unsaturated nitriles with Z-selectivity through direct α-C-H arylation of unmodified α,ß-unsaturated nitriles. The control experiments and DFT calculations support a four-stage reaction sequence, including the assembly of Tf2 O activated aryl sulfoxide with α,ß-unsaturated nitrile, MBH-like Lewis base addition, [3,3]-rearrangement, and E1cB-elimination. Among these stages, the Lewis base addition is diastereoselective and E1cB-elimination is cis-selective, which could account for the remarkable Z-selectivity of the reaction.

Flower-like droplets obtained by self-emulsification of a phase-separating (SEPS) aqueous film.

Self-emulsification, referring to the spontaneous formation of droplets of one phase in another immiscible phase, is attracting growing interest because of its simplicity in creating droplets. Existing self-emulsification methods usually rely on phase inversion, temperature cycling, and solvent evaporation. However, achieving spatiotemporal control over the morphology of self-emulsified droplets remains challenging. In this work, a conceptually new approach of creating both simple and complex droplets by self-emulsification of a phase-separating (SEPS) aqueous film, is reported. The aqueous film is formed by depositing a surfactant-laden aqueous droplet onto an aqueous surface, and the fragmentation of the film into droplets is triggered by a wetting transition. Smaller and more uniform droplets can be achieved by introducing liquid-liquid phase separation (LLPS). Moreover, properly modulating quadruple LLPS and film fragmentation enables the creation of highly multicellular droplets such as flower-like droplets stabilized by the interfacial self-assembly of nanoparticles. This work provides a novel strategy to design aqueous droplets by LLPS, and it will inspire a wide range of applications such as membraneless organelle synthesis, cell mimics and delivery.

LncRNA TTN-AS1/miR-134-5p/PAK3 axis regulates the radiosensitivity of human large intestine cancer cells through the P21 pathway and AKT/GSK-3ß/ß-catenin pathway.

Radiotherapy is an important adjuvant treatment for large intestine cancer even though it does not cause any response in many patients. The present study aimed to investigate the effects of the TTN antisense RNA 1 (TTN-AS1) long noncoding RNA (lncRNA) on radiotherapy dynamics of large intestine cancer cells and to explore the underlying molecular mechanisms. TTN-AS1 expression was evaluated by reverse-transcription quantitative polymerase chain reaction, western blot, and cellular immunofluorescence, and flow cytometry analysis was used to measure apoptosis. Radiotherapy was simulated in vitro by exposing cancer cells to X-ray. TTN-AS1 was highly expressed in large intestine cancer cells after an X-ray exposition for 24 hr. TTN-AS1 knockdown improved the radiosensitivity of large intestine cancer cells and promoted apoptosis by increasing Bax/Bcl2 protein expression and the active-caspase 3/caspase 3 ratios following X-ray treatment. In addition, TTN-AS1 negatively regulated miR-134-5p expression, and miR-134-5p-mimic transfection decreased PAK3 protein expression in large intestine cancer cells. Importantly, TTN-AS1 promoted PAK3 and P21 protein expression in HT29 cells after X-ray treatment. Moreover, the knockdown of P21 protein expression improved radiosensitivity and promoted X-ray-induced apoptosis of HT29 cells. Finally, PAK3 knockdown expression decreased the p-AKT/AKT and p-GSK-3ß/GSK-3ß ratios and promoted the ß-catenin transfer from the nucleus to the cytoplasm. These data suggest that the TTN-AS1 lncRNA promoted resistance to radiotherapy of large intestine cancer cells by increasing PAK3 expression via miR-134-5p inhibition, and this may be related to the P21 and AKT/GSK-3ß/ß-catenin pathway.

Hirudin Reduces the Expression of Markers of the Extracellular Matrix in Renal Tubular Epithelial Cells in a Rat Model of Diabetic Kidney Disease Through the Hypoxia-Inducible Factor-1α (HIF-1α)/Vascular Endothelial Growth Factor (VEGF) Signaling Pathway.

BACKGROUND This study aimed to investigate the effects of hirudin on the production of extracellular matrix (ECM) factors by renal tubular epithelial cells in a rat model of diabetic kidney disease (DKD) and HK-2 human renal tubule epithelial cells. MATERIAL AND METHODS Sprague-Dawley rats were divided into the normal control group (n=10), the normal control+hirudin group (n=10), the DKD model group (n=12) and the DKD+hirudin group (n=12). At the end of the study, renal histopathology was undertaken, and the expression of type IV collagen, fibronectin, hypoxia-inducible factor-1alpha (HIF-1alpha), and vascular endothelial growth factor (VEGF) were evaluated using immunohistochemistry, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). HK-2 cells were cultured in glucose and treated with hirudin. Protein and mRNA expression of fibronectin, type IV collagen, HIF-1alpha, and VEGF were evaluated following knockdown or overexpression of HIF-1alpha. RESULTS Hirudin significantly improved renal function in the rat model of DKD (P<0.01), and significantly down-regulated the expression of fibronectin, type IV collagen, HIF-1alpha, and VEGF proteins (P<0.05). The expression of ECM associated proteins was increased in HK-2 cells treated with high glucose and reduced in the high glucose+shRNA HIF-1alpha group (P<0.05). Compared with the control group, the expression of ECM associated proteins was increased in the HIF-1alpha over-expressed group, and decreased following treatment with hirudin (P<0.05). CONCLUSIONS Hirudin reduced the expression of markers of ECM by inhibiting the HIF-1alpha/VEGF signaling pathway in DKD renal tubular epithelial cells.

Dearomative Dual Functionalization of Aryl Iodanes.

Herein we describe the dearomatization of aryl iodanes through an unprecedented "rearrangement/addition" sequence. The process consists of two stages. First, a rapid [3,3] sigmatropic rearrangement of the aryl iodane with an α-stannyl nitrile affords a highly electrophilic dearomatized intermediate at -78 °C. A low-temperature rearrangement then enables the unstable dearomatized species to be trapped in situ with various nucleophiles. As a consequence, the reaction not only breaks the aromaticity of the aryl iodane but also sequentially installs two different functional groups, thus resulting in a polysubstituted alicyclic product.

The ortho-Difluoroalkylation of Aryliodanes with Enol Silyl Ethers: Rearrangement Enabled by a Fluorine Effect.

Presented herein is an intriguing effect of fluorine, and it allows difluoroenol silyl ethers to couple with aryliodanes in a redox-neutral manner to afford ortho-iodo difluoroalkylated arenes. The remaining iodide group provides a versatile platform for converting the products into various valuable difluoroalkylated arenes. The reaction shows excellent functional-group compatibility and broad substrate scope. A DFT mechanistic study suggests that the fluorine effect facilitates a subtle nucleophilic attack of the oxygen atom of enol silyl ethers onto aryliodanes, therefore leading to a rearrangement.

ERp44 depletion exacerbates ER stress and aggravates diabetic nephropathy in db/db mice.

Diabetic nephropathy (DN) is a major complication of diabetes, and the dysfunction of endoplasmic reticulum (ER) plays an important role in its pathogenesis. ERp44, an ER resident chaperone protein, has been implicated in the modulation of ER stress, however, its role and mechanism in DN are not determined. Here, we show that ERp44 expression is upregulated in the glomeruli of db/db mice, a rodent model of type 2 diabetes. When ERp44 is depleted by in vivo shRNA-mediated knockdown, the features associated with DN including albuminuria level and glomerular basement membrane (GBM) thickness are aggravated, therefore suggesting a detrimental role of ERp44 depletion in DN progression. We further show that ERp44 depletion exacerbates ER stress in DN in db/db mice, and that attenuating ER stress with the chemical chaperone TUDCA remarkably diminishes the aggravated DN features caused by ERp44 depletion. These results suggest that the exacerbated ER stress is a critical factor for the detrimental effect of ERp44 depletion on DN progression in db/db mice. Thus, our study links the role of ERp44 in DN with ER stress regulation and may offer a potential therapeutic strategy to interfere DN progression.

Selective ortho C-H Cyanoalkylation of (Diacetoxyiodo)arenes through [3,3]-Sigmatropic Rearrangement.

We herein report a robust catalyst-free cross-coupling between ArI(OAc)2 and α-stannyl nitriles, aided by TMSOTf. The transformation introduces a cyanoalkyl group to the ortho position of ArI(OAc)2 and simultaneously reduces the aryl iodine(III) to iodide, thus providing α-(2-iodoaryl) nitrile as the product. This transformation could be completed within 5 min at -78 °C and features superb functional-group tolerance and efficient scalability. DFT calculations indicate that the formation of a ketenimine(aryl)iodonium intermediate and subsequent [3,3]-sigmatropic rearrangement are involved as key steps.

Experimental investigation of influence of amide polymer on loess for subgrade.

The effects of moisture and drying shrinkage can lead to uneven settlement, cracking, and other diseases in loess subgrade. The objective of this study was to investigate the effects of amide polymer (AP) on the permeability, mechanical properties and crack resistance of loess by orthogonal experiments. The basic properties of AP and the permeability, mechanical properties, and dry-wet variation properties of polymer-modified loess were tested, and a scale model verification and simulation analysis were conducted. In this paper, water migration in subgrade is regulated by improving the water sensitivity of loess. By reducing the variation range of subgrade water content, the stress accumulation in subgrade caused by water is weakened. The results show that the curing time and mechanical properties of AP are directly affected by the oxidant and reducing agent, and the mechanical properties of AP are compatible with the characteristics of loess. AP filled the grain gap and reduced the permeability of loess by 34.05-280.83%. The ductility of polymer-modified loess is significantly increased, and the strain of peak strength is increased by 17.21-126.36%. AP can regulate moisture change, reduce the surface tension between particles, and reduce stress concentration. The strength loss rate was reduced by 19.98-51.21% by enhancing the cracking resistance and weakening the strength loss caused by dry and wet cycling. The increase of upper layer moisture content in the scale model of polymer-modified loess subgrade is reduced by 31.38-36.11%.

Robust and Wet Adhesive Self-Gelling Powders for Rapid Hemostasis and Efficient Wound Healing.

Healing traumatic wounds is arduous, leaving miscellaneous demands for ideal wound dressings, such as rapid hemostasis, superior wet tissue adhesion, strong mechanical properties, and excellent antibacterial activity. Herein, we report a self-gelling, wet adhesive, stretchable (polyethylenimine/poly(dimethylammonium chloride)/(poly(acrylic acid)/poly(sodium styrenesulfonate)/alkylated chitosan)) ((PEI/PDDA)/(PAA/PSS)/ACS) powder as a new option. The self-gel utilizes noncovalent interactions among in situ formed PDDA/PSS nanoparticles and PEI/PAA polymetric matrices to earn sensational mechanical properties and tensile strength while incorporating ACS to obtain fast hemostasis and therapeutic capacities. The powder can form a hydrogel patch in situ within 3 s upon liquid absorption, capable of resisting pressure higher than twice the blood pressure. Deposition of the self-gelling powders on various wounds, such as rat liver and femoral artery wounds, can stop bleeding in 10 s and lessen the amount of bleeding 6-fold plus in corresponding models. Furthermore, the self-gelling powders can significantly advance the chronic wound healing process by displaying a high wound healing rate and a low inflammatory response and promoting the formation of new blood vessels and tissue regeneration. The satisfactory mechanical properties, strong wet adhesion, sufficient antibacterial properties, ease of usage, adaptability to complex wounds, rapid hemostasis, and superior therapeutic capacities of (PEI/PDDA)/(PAA/PSS)/ACS self-gelling powders render them as a profound wound dressing biomaterial.