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With advances in technology and medical treatment, laparoscopy is increasingly used in hepatic cyst surgery. We hope that the analysis the safety and efficacy of laparoscopic hepatectomy versus open hepatectomy in giant hepatic cyst surgery will provide a theoretical basis for the choice of treatment means for clinicians.By searching CNKI (China National Knowledge Infrastructure), Wanfang, VIP (China Science and Technology Journal Database), CBM (China Biology Medicine disc), PubMed, Embase and Cochrane Library databases, all Chinese- and English-language articles on the safety and efficacy of laparoscopic hepatectomy and open hepatectomy for hepatic cysts were collected from database establishment to December 2021. Endnote X9 software was used for data checking and screening. Stata 15.1 software was used to analyze the relevant data. Sensitivity analysis was used to assess heterogeneity and funnel plots were used to detect bias in the results.A total of 43 relevant studies covering 3,375 patients with hepatic cysts were included: 1,733 patients in the laparoscopic hepatectomy group and 1,642 in the open hepatectomy group. Meta-analysis showed that the laparoscopic hepatectomy group had shorter operation time [standard mean difference (SMD) =-2.27, 95% confidence interval (CI): -2.63 to -1.92, P0.001], less intraoperative blood loss (SMD =-3.62, 95% CI: -4.22 to -3.02, P0.001), shorter hospital stay (SMD =-2.09, 95% CI: -2.41 to -1.78, P0.001), faster postoperative gastrointestinal function recovery (SMD =-3.94, 95% CI: -4.68 to -3.20, P0.001), and less postoperative complications [odds ratio (OR) =0.45, 95% CI: 0.35 to 0.58, P0.001] than the open hepatectomy group, with significant statistical differences. Sensitivity analyses were largely centered, and it indicates that the results have a high stability. The funnel plot was left-right symmetrical. It indicates that the intervention group was better than the control group and the results were reliable.There are significant differences in the safety and efficacy of laparoscopic hepatectomy compared with open hepatectomy. Laparoscopic hepatectomy can be selected to reduce postoperative pain. There were few foreign studies included, so whether our results apply to European and American populations still needs further study.

CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1), a well-characterized E3 ubiquitin ligase, is a central repressor of seedling photomorphogenic development in darkness. However, whether COP1 is involved in modulating abscisic acid (ABA) signaling in darkness remains largely obscure. Here, we report that COP1 is a positive regulator of ABA signaling during Arabidopsis seedling growth in the dark. COP1 mediates ABA-induced accumulation of ABI5, a transcription factor playing a key role in ABA signaling, through transcriptional and post-translational regulatory mechanisms. We further show that COP1 physically interacts with ABA-hypersensitive DCAF1 (ABD1), a substrate receptor of the CUL4-DDB1 E3 ligase targeting ABI5 for degradation. Accordingly, COP1 directly ubiquitinates ABD1 in vitro, and negatively regulates ABD1 protein abundance in vivo in the dark but not in the light. Therefore, COP1 promotes ABI5 protein stability post-translationally in darkness by destabilizing ABD1 in response to ABA. Interestingly, we reveal that ABA induces the nuclear accumulation of COP1 in darkness, thus enhancing its activity in propagating the ABA signal. Together, our study uncovers that COP1 modulates ABA signaling during seedling growth in darkness by mediating ABA-induced ABI5 accumulation, demonstrating that plants adjust their ABA signaling mechanisms according to their light environment.

It remains unknown and debatable how European-Asian–differentiated alleles affect individual phenotypes. Here, we made the first effort to analyze the expression profiles of highly differentiated genes with eastern and western origins in 90 Uyghurs using whole-genome (30× to 60×) and transcriptome data. We screened 921 872 east–west highly differentiated genetic variants, of which ∼4.32% were expression quantitative trait loci (eQTLs), ∼0.12% were alternative splicing quantitative trait loci (sQTLs), and ∼0.12% showed allele-specific expression (ASE). The 8305 highly differentiated eQTLs of strong effects appear to have undergone natural selection, associated with immunity and metabolism. European-origin alleles tend to be more biasedly expressed; highly differentiated ASEs were enriched in diabetes-associated genes, likely affecting the diabetes susceptibility in the Uyghurs. We proposed an admixture-induced expression model to dissect the highly differentiated expression profiles. We provide new insights into the genetic basis of phenotypic differentiation between Western and Eastern populations, advancing our understanding of the impact of genetic admixture.

Using genome-wide data of 89 ancient individuals dated to 5100 to 100 years before the present (B.P.) from 29 sites across the Tibetan Plateau, we found plateau-specific ancestry across plateau populations, with substantial genetic structure indicating high differentiation before 2500 B.P. Northeastern plateau populations rapidly showed admixture associated with millet farmers by 4700 B.P. in the Gonghe Basin. High genetic similarity on the southern and southwestern plateau showed population expansion along the Yarlung Tsangpo River since 3400 years ago. Central and southeastern plateau populations revealed extensive genetic admixture within the plateau historically, with substantial ancestry related to that found in southern and southwestern plateau populations. Over the past ~700 years, substantial gene flow from lowland East Asia further shaped the genetic landscape of present-day plateau populations. The high-altitude adaptive EPAS1 allele was found in plateau populations as early as in a 5100-year-old individual and showed a sharp increase over the past 2800 years.

Drought is a severe environmental condition that restricts the vegetative growth and reduces the yield of grapevine (Vitis vinifera L.). However, the mechanisms underlying grapevine response and adaptation to drought stress remain unclear. In the present study, we characterized an ANNEXIN gene, VvANN1, which plays a positive role in the drought stress response. The results indicated that VvANN1 was significantly induced by osmotic stress. Expression of VvANN1 in Arabidopsis thaliana enhanced osmotic and drought tolerance through modulating the level of MDA, H2O2, and O2·- at the seedling stage, implying that VvANN1 might be involved in the process of ROS homeostasis under drought or osmotic stress conditions. Moreover, we used yeast one-hybridization and chromatin immunoprecipitation assays to show that VvbZIP45 could regulate VvANN1 expression by directly binding to the promoter region of VvANN1 in response to drought stress. We also generated transgenic Arabidopsis that constitutively expressed the VvbZIP45 gene (35S::VvbZIP45) and further produced VvANN1Pro::GUS/35S::VvbZIP45 Arabidopsis plants via crossing. The genetic analysis results subsequently indicated that VvbZIP45 could enhance GUS expression in vivo under drought stress. Our findings suggest that VvbZIP45 may modulate VvANN1 expression in response to drought stress and reduce the impact of drought on fruit quality and yield.

Phytochrome A (phyA) is the far-red (FR) light photoreceptor in plants that is essential for seedling de-etiolation under FR-rich environments, such as canopy shade. TANDEM ZINC-FINGER/PLUS3 (TZP) was recently identified as a key component of phyA signal transduction in Arabidopsis thaliana; however, how TZP is integrated into the phyA signaling networks remains largely obscure. Here, we demonstrate that ELONGATED HYPOCOTYL5 (HY5), a well-characterized transcription factor promoting photomorphogenesis, mediates FR light induction of TZP expression by directly binding to a G-box motif in the TZP promoter. Furthermore, TZP physically interacts with CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), an E3 ubiquitin ligase targeting HY5 for 26S proteasome-mediated degradation, and this interaction inhibits COP1 interaction with HY5. Consistent with those results, TZP post-translationally promotes HY5 protein stability in FR light, and in turn, TZP protein itself is destabilized by COP1 in both dark and FR light conditions. Moreover, tzp hy5 double mutants display an additive phenotype relative to their respective single mutants under high FR light intensities, indicating that TZP and HY5 also function in largely independent pathways. Together, our data demonstrate that HY5 and TZP mutually upregulate each other in transmitting the FR light signal, thus providing insights into the complicated but delicate control of phyA signaling networks.

Acute myeloid leukemia (AML) refers to one of the most lethal blood malignancies worldwide. FLT3-ITD mutation is recognized as the most common one that predicted a poorer prognosis. There have been many prominent FLT3-ITD inhibitors approved by the FDA for clinical therapies. However, as impacted by undesirable off-target effects, differentiated metabolic issues, and clinical drug resistance problems, it remains challenging to discover alternative and promising solutions for treating FLT3-ITD+ AML. In this study, dovitinib was chemically modified and converted into CRBN-recruiting PROTACs. Two active compounds were identified, which showed enhanced antiproliferative effects against FLT3-ITD+ AML cells, both in vitro and in vivo. As demonstrated from further biological evaluation, the compounds could induce the degradation of the FLT3-ITD and KIT proteins in a ubiquitin-proteasome-dependent manner and completely block their downstream signaling pathway. The findings of this study would provide another promising strategy to develop novel therapies for FLT3-ITD+ AML.

Here is the pipeline describing the data processing in the manuscript for "Expression profiles of east-west highly differentiated genes in Uyghur genomes". The pipeline is applied to quantify expression data and conduct downstream enrichment analysis from fastq by samples.

In situ encapsulation of cellulase in conventional metal–organic frameworks (MOFs) is restrained by harsh preparation conditions and the rather small pores of the frameworks. Herein, We developed a mesoporous Zn-based MOF (Zn-mIm) prepared under mild conditions is well-suited for in situ encapsulation of cellulase. In brief, cellulase is encapsulated through coprecipitation of cellulase and Zn-mIm precursors, identified as cellulase@Zn-mIm. This approach enhances the binding between cellulase and Zn-mIm. The cellulase loading also significantly increases, and the highest loading is up to 350 mg g−1. Moreover, cellulase@Zn-mIm shows superior tolerance to basic environments and retains 65% of its activity at pH 8, whereas that of free cellulase drops to only 10%. Cellulase@Zn-mIm also exhibits good recyclability and retains 77% of its activity after four cycles. Furthermore, the introduction of cellulase leads to structural defects during Zn-mIm preparation, resulting in the formation of large pores, which facilitate mass transfer and thus enhance enzymatic efficiency.

A concise formal synthesis of (±)-aplykurodinone-1 starting from a commercially available material and based on the indium-catalyzed Conia-ene reaction has been accomplished. The synthesis features a Riley selenium dioxide oxidation, a Krapcho dealkoxycarbonylation, and a ring-closing metathesis approach. The synthetic strategy was also supported by a Saegusa oxidation and a classic Michael 1,4-conjugate addition.

Phytochromes are red (R) and far-red (FR) light photoreceptors in plants, and PHYTOCHROME-INTERACTING FACTORS (PIFs) are a group of basic helix-loop-helix family transcription factors that play central roles in repressing photomorphogenesis. Here, we report that MYB30, an R2R3-MYB family transcription factor, acts as a negative regulator of photomorphogenesis in Arabidopsis (Arabidopsis thaliana). We show that MYB30 preferentially interacts with the Pfr (active) forms of the phytochrome A (phyA) and phytochrome B (phyB) holoproteins and that MYB30 levels are induced by phyA and phyB in the light. It was previously shown that phytochromes induce rapid phosphorylation and degradation of PIFs upon R light exposure. Our current data indicate that MYB30 promotes PIF4 and PIF5 protein reaccumulation under prolonged R light irradiation by directly binding to their promoters to induce their expression and by inhibiting the interaction of PIF4 and PIF5 with the Pfr form of phyB. In addition, our data indicate that MYB30 interacts with PIFs and that they act additively to repress photomorphogenesis. In summary, our study demonstrates that MYB30 negatively regulates Arabidopsis photomorphogenic development by acting to promote PIF4 and PIF5 protein accumulation under prolonged R light irradiation, thus providing new insights into the complicated but delicate control of PIFs in the responses of plants to their dynamic light environment.

In this paper, a Rh-catalyzed diastereoselective α-allylation of cycloenamines is demonstrated. During the reaction, commercially available Wilkinson's catalyst was employed, and a chiral sulfinamide group acted as the chiral directing group. Following such a synthetic method, unusual linear substituted products were achieved, instead of branched substituted products which were most reported previously. The reaction exhibits a good chemical yield and excellent diastereoselectivity. A possible reaction mechanism was proposed. The method should be conducive to synthesizing natural products and novel drug molecules.

A dual-functional urea-linked conjugated porous polymer (UCPP) assembled by enol–imine with ordered unit arrays that act as potential anchoring sites in the networks was fabricated, and was further applied as a support for Ag nanoparticles by the coordinate interaction between them. The UCPP not only can well confine the Ag particle size and facilitate high dispersion, but also can afford special CO2-philic moieties to enhance the adsorption properties. The resulting Ag@UCPP as a heterogeneous catalyst exhibited excellent activity for the carboxylative cyclization of propargyl alcohols with CO2 under mild conditions, together with good recyclability, which is probably attributed to the synergistic effect of the UCPP on the adsorption and activation of CO2 and the immobilization of Ag nanoparticles. This work affords possible opportunities for the design and synthesis of a heterogeneous catalyst toward CO2 conversion.

Owing to the potential of sodium as an alternative to lithium as charge carrier, increasing attention has been focused on the development of high-performance electrolytes for Na batteries in recent years. In this regard, gel-type electrolytes, which combine the outstanding ionic conductivity of liquid electrolytes and the safety of solid electrolytes, demonstrate immense application prospects. However, most gel electrolytes not only need a number of specific techniques for molding, but also typically suffer from breakage, leading to a short service life and severe safety issues. In this study, a supramolecular thixotropic ionogel electrolyte is proposed to address these problems. This thixotropic electrolyte is formed by the supramolecular self-assembly of D-gluconic acetal-based gelator (B8) in an ionic liquid solution of a Na salt, which exhibits moldability, a high ionic conductivity, and a rapid self-healing property. The ionogel electrolyte is chemically stable to Na and exhibits a good Na+ transference number. In addition, the self-assembly mechanism of B8 and thixotropic mechanism of ionogel are investigated. The safe, low-cost and multifunctional ionogel electrolyte developed herein supports the development of future high-performance Na batteries.

Objective To systematically evaluate the relationship between vascular endothelial growth factor (VEGF) and prognosis of intrahepatic cholangiocarcinoma by meta-analysis. Methods We systematically searched relevant studies in the databases of PubMed, Embase, Cochrane Library, CNKI, Wangfang, and Web of Science, with search dates limited to September 1, 2021. We extracted relevant data, including prognosis and clinicopathological features of patients with different expressions of VEGF in intrahepatic cholangiocarcinoma. The combined hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) were calculated to evaluate the link strength between VEGF and prognosis of cholangiocarcinoma patients. Results A total of 7 eligible studies with 495 patients were included in this meta-analysis. The results showed that the high expression of VEGF was significantly related to poor overall survival (OS) (HR = 1.93, 95% CI 1.52–2.46, P < 0.05) in patients with intrahepatic cholangiocarcinoma. Moreover, high expression of VEGF in tumor tissues associated with lymph node metastasis (LNM) (OR = 6.79, 95% CI 3.93–11.73, P < 0.05) and advanced TNM stage (OR = 4.35, 95% CI 2.34–8.07, P < 0.05) in intrahepatic cholangiocarcinoma. Sensitivity analysis shows that the meta-analysis results are stable and reliable. Conclusion The expression of VEGF is related to the OS of patients with intrahepatic cholangiocarcinoma, and the OS of patients with high expression of VEGF is shorter. VEGF may be a novel predictor of intrahepatic cholangiocarcinoma patients. Trial registration PROSPERO (CRD42022297443).

The homeostasis of histone methylation is maintained by histone methyltransferases and demethylases, which are important for the regulation of gene expression. Here, we report a histone demethylase from rice (Oryza sativa), Jumonji C domain-containing protein (JMJ710), which belongs to the JMJD6 group and plays an important role in the response to drought stress. Overexpression of JMJ710 causes a drought-sensitive phenotype, while RNAi and clustered regularly interspaced short palindromic repeats (CRISPR)-knockout mutant lines show drought tolerance. In vitro and in vivo assays showed that JMJ710 is a histone demethylase. It targets to MYB TRANSCRIPTION FACTOR 48 (MYB48-1) chromatin, demethylates H3K36me2, and negatively regulates the expression of MYB48-1, a positive regulator of drought tolerance. Under drought stress, JMJ710 is downregulated and the expression of MYB48-1 increases, and the subsequent activation of its downstream drought-responsive genes leads to drought tolerance. This research reports a negative regulator of drought stress-responsive genes, JMJ710, that ensures that the drought tolerance mechanism is not mis-activated under normal conditions but allows quick activation upon drought stress.

Background: Intrahepatic duct (IHD) stones, also known as hepatolithiasis, refers to any intrahepatic stones of the left and right hepatic ducts. It is a benign biliary tract disease with a high recurrence rate, with many complications, and difficulty in radical cure. The aim of this review and meta-analysis is to compare the safety and efficacy of the laparoscopic left lateral hepatectomy (LLLH) and open left lateral hepatectomy (OLLH) for IHD stones.Methods: Pubmed, Embase, Cochrane, WangFang Data, and China National Knowledge Infrastructure were searched for randomized controlled trials (RCTs) regarding the comparison of LLLH and OLLH in the treatment of hepatolithiasis. Standard mean difference (SMD), odds ratio (OR), and 95% CI were calculated using the random-effects model or fixed-effects model according to the heterogeneity between studies.Results: From January 01, 2001 to May 30, 2021, 1,056 articles were retrieved, but only 13 articles were finally included for the meta-analysis. The results showed that compared to the OLLH group, LLLH resulted in smaller surgical incision, less intraoperative blood loss, faster postoperative recovery, and fewer postoperative complications (surgical incision: SMD = −3.76, 95% CI: −5.40, −2.12; intraoperative blood loss: SMD = −0.95, 95% CI: −1.69, −0.21; length of hospital stay: SMD = −1.56, 95% CI: −2.37, −0.75; postoperative complications: OR = 0.45, 95% CI: 0.26, 0.78).Conclusions: In the treatment of hepatolithiasis, compared with OLLH, LLLH has the advantages of less intraoperative blood loss, smaller incisions, less postoperative complications, shorter hospital stay, shorter time to first postoperative exhaust, and postoperative ambulation, and rapid postoperative recovery.

Drought is a major abiotic stress limiting crop growth and yield. In this study, we characterized a novel drought tolerance induced WIH gene in rice, OsWIH2. Overexpression of OsWIH2 in rice resulted in significantly higher drought tolerance, probably due to the decreased water loss rate and reactive oxygen species (ROS) accumulation under drought stress. We identified a long-chain fatty acid HOTHEAD (HTH) that interacted with OsWIH2 using yeast two-hybrid screening. OsWIH2 is an enzyme which is involved in fatty acid synthesis. We further demonstrated that the drought-inducible bHLH transcription factor OsbHLH130 could activate the expression of OsWIH2. Overall, our results suggest that drought stress may induce OsbHLH130 accumulation, which in turn activates OsWIH2 expression, and the latter improves rice drought tolerance by participating in cuticular wax biosynthesis and reducing the water loss rate as well as ROS accumulation. This research provides new genes for crop improvement.

In the management of severe accident of nuclear reactor, the pressure relief of reactor coolant system (RCS) is an important mitigation measure to prevent high pressure core melt (HPCM). In the safety system improvement of Tianwan56 nuclear power plant, the optimization measure of adding the dedicated pressure relief valve (DPRV) for severe accident were adopted. This improvement allows the reactor to release the pressure of RCS before the reactor vessel being damaged to mitigate the consequence of reactor melt accident under high-pressure condition. Based on the analysis of severe accident sequences, the total loss of feed water accident is confirmed to cover the various severe accident consequences which may lead to HPCM accident. This paper studied the transient characteristics of total loss of feed water accident sequences, and the factors such as valve opening delay on the operating temperature of the valve were researched. Finally, the representative and envelope operating condition of DPRV under severe accident was clarified. Besides, the temperature curve of fluid passing through the valve and the maximum temperature the valve experienced were obtained. This research provides the valuable and indispensable basis to the operability and integrity analysis of DPRV in severe accident.

Sustainable architectural education is offered in colleges and universities all over the world. Studies have emphasized the importance of sustainable architectural education in introductory courses of architecture major programs, but methods and strategies for teaching sustainable architecture at lower levels are scarce. This study focuses on the design-to-physical-construction process and creates a teaching framework that incorporates the concept of sustainable development from the perspectives of sustainable economy, environment and society. Based on the teaching method of learning through the design-to-physical-construction process and referring to the grounded theory, a case study on a bamboo construction project was conducted to explore approaches and strategies of sustainable architectural education in introductory courses. Results reveal that five systems, including the system of sustainable development, consist of a framework that illustrated the teaching effects. Based on the framework, we discovered five factors that should be considered in incorporating the concept of sustainable development into architectural design teaching, including the necessity of conducting sustainable architectural education in introductory courses. This study helps explore the potential role sustainability plays in incorporating interdisciplinary knowledge, connecting specialized knowledge across different program levels, and motivating student learning. It also provides a reference for the practice of sustainable architectural education.

Structural variants (SVs) may play important roles in human adaptation to extreme environments such as high altitude but have been under-investigated. Here, combining long-read sequencing with multiple scaffolding techniques, we assembled a high-quality Tibetan genome (ZF1), with a contig N50 length of 24.57 mega-base pairs (Mb) and a scaffold N50 length of 58.80 Mb. The ZF1 assembly filled 80 remaining N-gaps (0.25 Mb in total length) in the reference human genome (GRCh38). Markedly, we detected 17 900 SVs, among which the ZF1-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway. Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese. This deletion is significantly associated with lower systolic pulmonary arterial pressure, one of the key adaptive physiological traits in Tibetans. Moreover, with the use of the high-quality de novo assembly, we observed a much higher rate of genome-wide archaic hominid (Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1 (1.32%–1.53%) compared to other East Asian genomes (0.70%–0.98%), reflecting a unique genomic composition of Tibetans. One such archaic hominid shared sequence—a 662-bp intronic insertion in the SCUBE2 gene—is enriched and associated with better lung function (the FEV1/FVC ratio) in Tibetans. Collectively, we generated the first high-resolution Tibetan reference genome, and the identified SVs may serve as valuable resources for future evolutionary and medical studies.

As the largest ethnic group in the world, the Han Chinese population is nonetheless underrepresented in global efforts to catalogue the genomic variability of natural populations. Here, we developed the PGG.Han, a population genome database to serve as the central repository for the genomic data of the Han Chinese Genome Initiative (Phase I). In its current version, the PGG.Han archives whole-genome sequences or high-density genome-wide single-nucleotide variants (SNVs) of 114 783 Han Chinese individuals (a.k.a. the Han100K), representing geographical sub-populations covering 33 of the 34 administrative divisions of China, as well as Singapore. The PGG.Han provides: (i) an interactive interface for visualization of the fine-scale genetic structure of the Han Chinese population; (ii) genome-wide allele frequencies of hierarchical sub-populations; (iii) ancestry inference for individual samples and controlling population stratification based on nested ancestry informative markers (AIMs) panels; (iv) population-structure-aware shared control data for genotype-phenotype association studies (e.g. GWASs) and (v) a Han-Chinese-specific reference panel for genotype imputation. Computational tools are implemented into the PGG.Han, and an online user-friendly interface is provided for data analysis and results visualization. The PGG.Han database is freely accessible via http://www.pgghan.org or https://www.hanchinesegenomes.org.

Human genetic adaptation to high altitudes (>2500 m) has been extensively studied over the last few years, but few functional adaptive genetic variants have been identified, largely owing to the lack of deep-genome sequencing data available to previous studies. Here, we build a list of putative adaptive variants, including 63 missense, 7 loss-of-function, 1,298 evolutionarily conserved variants and 509 expression quantitative traits loci. Notably, the top signal of selection is located in TMEM247, a transmembrane protein-coding gene. The Tibetan version of TMEM247 harbors one high-frequency (76.3%) missense variant, rs116983452 (c.248C > T; p.Ala83Val), with the T allele derived from archaic ancestry and carried by >94% of Tibetans but absent or in low frequencies (

We describe a concise and straightforward approach to the total syntheses of (+)-Strictifolione and Cryptofolione in the longest linear sequences of four steps and six steps from 3-phenyl propanal and trans-cinnamaldehyde, respectively. The route utilized a titanium tetraisopropoxide/(R)-[1,1'-binaphthalene]-2,2'-diol catalyzed Mukaiyama aldol reaction, indium(0)-promoted Barbier reaction, and olefin cross-metathesis as the key reactions.

Reactions of thiocarbonyl fluoride derived from cheap, readily available, and widely used CF3SiMe3, elemental sulfur, and KF with secondary amines and primary amines at room temperature in THF provided a wide variety of thiocarbamoyl fluorides and isothiocyanates in moderate to excellent yields, respectively. The two reactions show broad substrate scope and good functional group tolerance. Moreover, AgSCF3 reacts with secondary/primary amines under KBr at room temperature, affording quantitative thiocarbamoyl fluorides/isothiocyanates, which feature late-stage application.

We describe a new and straightforward approach to the formal synthesis of the hepatitis B virus inhibitor entecavir, an important hepatitis B drug, in ten steps overall. Key features of the route are a Morita–Baylis–Hillman reaction, a Sharpless asymmetric epoxidation, a reductive epoxide opening of an α,β-epoxy ketone, and a Riley selenium dioxide oxidation.

A concise and straightforward formal synthesis of (±)-aplykurodinone-1, a degraded steroid natural product isolated from sea hare Syphonota geographica is described, based on an intramolecular Michael addition. The route also includes an intermolecular Michael addition, a Riley selenium dioxide oxidation, and a Krapcho dealkoxycarbonylation. The relative stereochemistries of key intermediates have been determined through single-crystal X-ray diffraction analysis.

A unified asymmetric total synthesis of (+)-porantheridine and (−)-6-epi-porantheridine has been accomplished. The two molecules were prepared via a Horner–Wadsworth–Emmons/aza-Michael addition reaction or diastereoselective nucleophilic substitution of 2-methoxypiperidine from a common intermediate, respectively. The key features of the unified synthetic strategy also included an asymmetric addition of silyl dienolate to sulfinylimine, substrate-controlled reduction, Wacker oxidation and TFA-promoted cyclization.

The statistical power of genome-wide association studies (GWASs) is affected by the effective sample size. However, the privacy and security concerns associated with individual-level genotype data pose great challenges for cross-institutional cooperation. The full-process cryptographic solutions are in demand but have not been covered, especially the essential principal-component analysis (PCA). Here, we present TrustGWAS, a complete solution for secure, large-scale GWAS, recapitulating gold standard results against PLINK without compromising privacy and supporting basic PLINK steps including quality control, linkage disequilibrium pruning, PCA, chi-square test, Cochran-Armitage trend test, covariate-supported logistic regression and linear regression, and their sequential combinations. TrustGWAS leverages pseudorandom number perturbations for PCA and multiparty scheme of multi-key homomorphic encryption for all other modules. TrustGWAS can evaluate 100,000 individuals with 1 million variants and complete QC-LD-PCA-regression workflow within 50 h. We further successfully discover gene loci associated with fasting blood glucose, consistent with the findings of the ChinaMAP project.

Natural polysaccharides and their metabolites’ short chain fatty acids (SCFAs) have attracted much attention. Recently, they have shown great potential in attenuating systemic inflammation activities, especially in inflammatory bowel disease (IBD). IBD is a complex pathological process and is related to epithelial damage and microbiota imbalance in the gut. Recent studies have indicated that natural polysaccharides could improve IBD recovery by different mechanisms. They could not only influence the ratio of intestine microbiota, but also regulate the secretion levels of immunity cytokines through multiple pathways, the latter including modulation of the TLR/MAPK/NF-κB signaling pathways and stimulation of G-protein-coupled receptors. Moreover, they could increase intestinal integrity and modulate oxidative stress. In this review, recent research about how natural polysaccharides impact the pathogenesis of IBD are summarized to prove the association between polysaccharides and disease recovery, which might contribute to the secretion of inflammatory cytokines, improve intestine epithelial damage, reduce oxidative stress, sustain the balanced microenvironment of the intestines, and finally lower the risk of IBD.

Background Plant annexins are calcium- and lipid-binding proteins that have multiple functions, and a significant amount of research on plant annexins has been reported in recent years. However, the functions of annexins in diverse biological processes in rice are largely unclear. Results Herein, we report that OsANN4, a calcium-binding rice annexin protein, was induced by abscisic acid (ABA). Under ABA treatment, the plants in which OsANN4 was knocked down by RNA interference showed some visible phenotypic changes compared to the wild type, such as a lower rooting rate and shorter shoot and root lengths. Moreover, the superoxide dismutase (SOD) and catalase (CAT) activities of the RNAi lines were significantly lower and further resulted in higher accumulation of O2.- and H2O2 than those of the wild-type. A Non-invasive Micro-test Technology (NMT) assay showed that ABA-induced net Ca2+ influx was inhibited in OsANN4 knockdown plants. Interestingly, the phenotypic differences caused by ABA were eliminated in the presence of LaCl3 (Ca2+ channel inhibitor). Apart from this, we demonstrated that OsCDPK24 interacted with and phosphorylated OsANN4. When the phosphorylated serine residue of OsANN4 was substituted by alanine, the interaction between OsANN4 and OsCDPK24 was still observed, however, both the conformation of OsANN4 and its binding activity with Ca2+ might be changed. Conclusions OsANN4 plays a crucial role in the ABA response, partially by modulating ROS production, mediating Ca2+ influx or interacting with OsCDPK24. Supplementary Information The online version contains supplementary material available at 10.1186/s12870-021-03248-3.

A dual-functional urea-linked conjugated porous polymer (UCPP) assembled by enol-imine with ordered unit arrays that act as potential anchoring sites in the networks was fabricated, and was further applied as a support for Ag nanoparticles by the coordinate interaction between them. The UCPP not only can well confine the Ag particle size and facilitate high dispersion, but also can afford special CO

Light and temperature are two core environmental factors that coordinately regulate plant growth and survival throughout their entire life cycle. However, the mechanisms integrating light and temperature signaling pathways in plants remain poorly understood. Here, we report that CBF1, an AP2/ERF-family transcription factor essential for plant cold acclimation, promotes hypocotyl growth under ambient temperatures in Arabidopsis. We show that CBF1 increases the protein abundance of PIF4 and PIF5, two phytochrome-interacting bHLH-family transcription factors that play pivotal roles in modulating plant growth and development, by directly binding to their promoters to induce their gene expression, and by inhibiting their interaction with phyB in the light. Moreover, our data demonstrate that CBF1 promotes PIF4/PIF5 protein accumulation and hypocotyl growth at both 22°C and 17°C, but not at 4°C, with a more prominent role at 17°C than at 22°C. Together, our study reveals that CBF1 integrates light and temperature control of hypocotyl growth by promoting PIF4 and PIF5 protein abundance in the light, thus providing insights into the integration mechanisms of light and temperature signaling pathways in plants.

A series of non-conjugated methylene–anthracene Schiff base derivatives (DNCAs) were designed and synthesized. Photoluminescence emission spectra indicated that DNCA-4 and DNCA-12 showed obviously mechanofluorochromic properties, and distinctive 26- and 37-nm hypochromic shifts were observed, respectively. The experiment results revealed that there is no specific relationship between alkoxy chain lengths and their stimuli–response behavior. The PXRD profiles demonstrated a transformation from crystalline to amorphous state upon grinding.

Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28-37×. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans ~ 50-33 thousand years ago (kya), followed by East Asian (~ 40-15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component.

High-performance electrochromic materials with high optical contrast, coloration efficiency, and excellent stability have always been critical for polymer electrochromics, and will boost diverse applications including flexible displays and wearable electronics. Herein, we develop a donor-acceptor-donor type copolymer from strong electron-withdrawing acceptor unit isoindigo and electron-donating moiety bis-EDOT by synthesizing and electropolymerizing its precursor (E)-1,1′-dihexyl-6,6′-bis(2,2′,3,3′-tetrahydro-[5,5′-bithieno[3,4-b][1,4]dioxin]-7-yl)-[3,3′-biindolinylidene]-2,2′‑dione (BisE−IDOH−BisE). Such polymer exhibits a low optical bandgap of 1.02 eV with stable and reversible electrochromism from kelly-green to sky blue. Further kinetic studies demonstrate that this polymer displays intriguing overall electrochromic performances throughout the NIR window with simultaneously high optical contrast up to 90%, high coloration efficiency of 1025 cm2 C−1, fast switching time of 1.1 s, and excellent reversible stability (

Background Copy number variation (CNV) is a valuable source of genetic diversity in the human genome and a well-recognised cause of various genetic diseases. However, CNVs have been considerably under-represented in population-based studies, particularly the Han Chinese which is the largest ethnic group in the world. Objectives To build a representative CNV map for the Han Chinese population. Methods We conducted a genome-wide CNV study involving 451 male Han Chinese samples from 11 geographical regions encompassing 28 dialect groups, representing a less-biased panel compared with the currently available data. We detected CNVs by using 4.2M NimbleGen comparative genomic hybridisation array and whole-genome deep sequencing of 51 samples to optimise the filtering conditions in CNV discovery. Results A comprehensive Han Chinese CNV map was built based on a set of high-quality variants (positive predictive value >0.8, with sizes ranging from 369 bp to 4.16 Mb and a median of 5907 bp). The map consists of 4012 CNV regions (CNVRs), and more than half are novel to the 30 East Asian CNV Project and the 1000 Genomes Project Phase 3. We further identified 81 CNVRs specific to regional groups, which was indicative of the subpopulation structure within the Han Chinese population. Conclusions Our data are complementary to public data sources, and the CNV map may facilitate in the identification of pathogenic CNVs and further biomedical research studies involving the Han Chinese population.

Background The genetic relationships reported by recent studies between Sherpas and Tibetans are controversial. To gain insights into the population history and the genetic basis of high-altitude adaptation of the two groups, we analyzed genome-wide data in 111 Sherpas (Tibet and Nepal) and 177 Tibetans (Tibet and Qinghai), together with available data from present-day human populations. Results Sherpas and Tibetans show considerable genetic differences and can be distinguished as two distinct groups, even though the divergence between them (~3200–11,300 years ago) is much later than that between Han Chinese and either of the two groups (~6200–16,000 years ago). Sub-population structures exist in both Sherpas and Tibetans, corresponding to geographical or linguistic groups. Differentiation of genetic variants between Sherpas and Tibetans associated with adaptation to either high-altitude or ultraviolet radiation were identified and validated by genotyping additional Sherpa and Tibetan samples. Conclusions Our analyses indicate that both Sherpas and Tibetans are admixed populations, but the findings do not support the previous hypothesis that Tibetans derive their ancestry from Sherpas and Han Chinese. Compared to Tibetans, Sherpas show higher levels of South Asian ancestry, while Tibetans show higher levels of East Asian and Central Asian/Siberian ancestry. We propose a new model to elucidate the differentiated demographic histories and local adaptations of Sherpas and Tibetans. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1242-y) contains supplementary material, which is available to authorized users.

Aculeatin A, isolated from the plant Amomum aculeatum, is a dispirocyclic compound having antimalarial activity. In this paper, we describe a novel synthetic approach to aculeatin A from 1-tetradecanal in nine steps via a stepwise strategy. The key features of this approach include the 1,3-diketone preparation from Claisen condensation of ketone and acyl chloride, cyclodehydration, and intramolecular oxa-Michael addition to 2,3-dihydro-4H-pyran-4-one.