Thiol-based chemical probes exhibit antiviral activity against SARS-CoV-2 via allosteric disulfide disruption in the spike glycoprotein.

The development of small-molecules targeting different components of SARS-CoV-2 is a key strategy to complement antibody-based treatments and vaccination campaigns in managing the COVID-19 pandemic. Here, we show that two thiol-based chemical probes that act as reducing agents, P2119 and P2165, inhibit infection by human coronaviruses, including SARS-CoV-2, and decrease the binding of spike glycoprotein to its receptor, the angiotensin-converting enzyme 2 (ACE2). Proteomics and reactive cysteine profiling link the antiviral activity to the reduction of key disulfides, specifically by disruption of the Cys379-Cys432 and Cys391-Cys525 pairs distal to the receptor binding motif in the receptor binding domain (RBD) of the spike glycoprotein. Computational analyses provide insight into conformation changes that occur when these disulfides break or form, consistent with an allosteric role, and indicate that P2119/P2165 target a conserved hydrophobic binding pocket in the RBD with the benzyl thiol-reducing moiety pointed directly toward Cys432. These collective findings establish the vulnerability of human coronaviruses to thiol-based chemical probes and lay the groundwork for developing compounds of this class, as a strategy to inhibit the SARS-CoV-2 infection by shifting the spike glycoprotein redox scaffold.

DGW1, encoding an hnRNP-like RNA binding protein, positively regulates grain size and weight by interacting with GW6 mRNA.

Grain size and weight determine rice yield. Although numerous genes and pathways involved in regulating grain size have been identified, our knowledge of post-transcriptional control of grain size remains elusive. In this study, we characterize a rice mutant, decreased grain width and weight 1 (dgw1), which produces small grains. We show that DGW1 encodes a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family protein and preferentially expresses in developing panicles, positively regulating grain size by promoting cell expansion in spikelet hulls. Overexpression of DGW1 increases grain weight and grain numbers, leading to a significant rise in rice grain yield. We further demonstrate that DGW1 functions in grain size regulation by directly binding to the mRNA of Grain Width 6 (GW6), a critical grain size regulator in rice. Overexpression of GW6 restored the grain size phenotype of DGW1-knockout plants. DGW1 interacts with two oligouridylate binding proteins (OsUBP1a and OsUBP1b), which also bind the GW6 mRNA. In addition, the second RRM domain of DGW1 is indispensable for its mediated protein-RNA and protein-protein interactions. In summary, our findings identify a new regulatory module of DGW1-GW6 that regulates rice grain size and weight, providing important insights into the function of hnRNP-like proteins in the regulation of grain size.

Thalamic gray matter volume mediates the association between KIBRA polymorphism and olfactory function among older adults: a population-based study.

The kidney and brain expressed protein (KIBRA) rs17070145 polymorphism is associated with both structure and activation of the olfactory cortex. However, no studies have thus far examined whether KIBRA can be linked with olfactory function and whether brain structure plays any role in the association. We addressed these questions in a population-based cross-sectional study among rural-dwelling older adults. This study included 1087 participants derived from the Multidomain Interventions to Delay Dementia and Disability in Rural China, who underwent the brain MRI scans in August 2018 to October 2020; of these, 1016 took the 16-item Sniffin' Sticks identification test and 634 (62.40%) were defined with olfactory impairment (OI). Data were analyzed using the voxel-based morphometry analysis and general linear, logistic, and structural equation models. The KIBRA rs17070145 C-allele (CC or CT vs. TT genotype) was significantly associated with greater gray matter volume (GMV) mainly in the bilateral orbitofrontal cortex and left thalamus (P < 0.05) and with the multi-adjusted odds ratio of 0.73 (95% confidence interval 0.56-0.95) for OI. The left thalamic GMV could mediate 8.08% of the KIBRA-olfaction association (P < 0.05). These data suggest that the KIBRA rs17070145 C-allele is associated with a reduced likelihood of OI among older adults, partly mediated through left thalamic GMV.

Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

MiR-196b-3p and miR-450b-3p are key regulators of adipogenesis in porcine intramuscular and subcutaneous adipocytes.

BACKGROUND: As components of white adipose tissue, porcine intramuscular (IM) and subcutaneous (SC) adipocytes undergo similar differentiation and adipogenesis processes. However, the adipogenic capacity of IM adipocytes is weaker than that of SC adipocytes. Identifying key regulators underlying this difference between IM and SC adipocytes will benefit pig breeding. RESULTS: In this study, we used BGISEQ-500 sequencing technology to analyze the expression of small RNAs in primary cultured IM and SC adipocytes on day 8 after adipogenic induction, and found 32-fold higher miR-196b-3p expression, as well as 8-fold lower miR-450b-3p expression in IM adipocytes than in SC adipocytes. Functional studies revealed that miR-196b-3p inhibits adipogenesis by targeting CD47 via the AMPK signaling pathway, and its effect was attenuated by the specific p-AMPKα activator AICAR. We also found that miR-450b-3p promotes adipogenesis by targeting SIRT1 via the Wnt/ß-catenin signaling pathway, and its effect was weakened by the Wnt/ß-catenin signaling activator LiCl. CONCLUSIONS: Our findings suggest that miR-196b-3p and miR-450b-3p are novel key regulatory factors that play opposite roles in porcine adipogenesis, helping us decipher the regulatory differences between porcine IM and SC fat deposition.

Physical activity and eating behaviors patterns associated with high blood pressure among Chinese children and adolescents.

BACKGROUND: Physical activity and eating behavior are associated with hypertension in children and adolescents. Revealing the associations between physical activity patterns, eating behavior patterns and high blood pressure (HBP) could help improve the problem of hypertension from the actual children's physical activities and eating behaviors. METHODS: A total of 687 students aged 8-15 years were selected from two nine-year primary and secondary schools using stratified cluster random sampling method. The students' body height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, and their physical activity time and eating behaviors were surveyed by using CLASS questionnaire and self-made eating behavior questionnaire, respectively. Exploratory factor analysis (EFA) was used to extract moderate to vigorous physical activity factor (MVPAF), sedentary activity factor (SAF), healthy eating behavior factor (HEBF), unhealthy eating behavior factor (UHEBF). MVPAF ≥ SAF was defined as moderate to vigorous physical activity pattern (MVPAP), MVPAF < SAF was defined as sedentary activity pattern (SAP). HEBF ≥ UHEBF was defined as healthy eating behavior pattern (HEBP), while the opposite was defined as unhealthy eating behavior pattern (UHEBP). Lifestyles includes physical activity patterns and eating behavior patterns. RESULTS: The overall prevalence of hypertension was 5.8% (40/687), and was 5.69% (21/369) in boys and 5.97% (19/318) in girls, respectively. The MVPAF and UHEBF in boys were significantly higher than those in girls (P < 0.01), while the SAF in girls was significantly higher than that in boys (P < 0.05). The SAF was positively correlated with SBP in girls (ß(SE) = 0.14 (0.50), P = 0.016), and was positively correlated with SBP (ß(SE) = 0.21 (1.22), P = 0.000 and DBP (ß(SE) = 0.14 (0.49), P = 0.006) in boys. The MVPAF was negatively correlated with DBP (ß(SE)=-0.11 (0.40), P = 0.022) in boys. In boys, the SAP increased the risks of HBP (OR (95% CI):3.34 (1.30-8.63)) and high DBP (OR (95% CI):3.08 (1.02-9.34)) compared with MVPAP. CONCLUSION: Compared with the boys with MVPAP, boys with SAP may increase the risks of HBP and high DBP. The SAF may be positively associated with SBP in boys and girls, while the MVPAF may be negatively associated with DBP in boys.

Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults.

Olfactory impairment is a potential marker for prodromal dementia, but the underlying mechanisms are poorly understood. This population-based study included 4214 dementia-free participants (age ≥65 years). Olfaction was assessed using the 16-item Sniffin' Sticks identification test. In the subsamples, we measured plasma amyloid beta (Aß)40, Aß42, total tau, and neurofilament light chain (NfL; n = 1054); and quantified hippocampal, entorhinal cortex, and white matter hyperintensity (WMH) volumes, and Alzheimer's disease (AD)-signature cortical thickness (n = 917). Data were analyzed with logistic and linear regression models. In the total sample, mild cognitive impairment (MCI) was diagnosed in 1102 persons (26.2%; amnestic MCI, n = 931; non-amnestic MCI, n = 171). Olfactory impairment was significantly associated with increased likelihoods of MCI, amnestic MCI, and non-amnestic MCI. In the subsamples, anosmia was significantly associated with higher plasma total tau and NfL concentrations, smaller hippocampal and entorhinal cortex volumes, and greater WMH volume, and marginally with lower AD-signature cortical thickness. These results suggest that cerebral neurodegenerative and microvascular lesions are common neuropathologies linking anosmia with MCI in older adults.

In Situ Preparation of Three-Dimensional Porous Nickel Sulfide as a Battery-Type Supercapacitor.

A one-step sulfurization method to fabricate Ni3S2 nanowires (Ni3S2 NWs) directly on a Ni foam (NF) was developed as a simple, low-cost synthesis method for use as a supercapacitor (SC), aimed at optimizing energy storage. Ni3S2 NWs have high specific capacity and are considered a promising electrode material for SCs; however, their poor electrical conductivity and low chemical stability limit their applications. In this study, highly hierarchical three-dimensional porous Ni3S2 NWs were grown directly on NF by a hydrothermal method. The feasibility of the use of Ni3S2/NF as a binder-free electrode for achieving high-performance SCs was examined. Ni3S2/NF exhibited a high specific capacity (255.3 mAh g-1 at a current density of 3 A g-1), good rate capability (2.9 times higher than that of the NiO/NF electrode), and competitive cycling performance (capacity retention of specific capacity of 72.17% after 5000 cycles at current density of 20 A g-1). Owing to its simple synthesis process and excellent performance as an electrode material for SCs, the developed multipurpose Ni3S2 NWs electrode is expected to be a promising electrode for SC applications. Furthermore, the synthesis method of self-growing Ni3S2 NW electrodes on 3D NF via hydrothermal reactions could potentially be applied to the fabrication of SC electrodes using a variety of other transition metal compounds.

Benchmarking Cleavable Biotin Tags for Peptide-Centric Chemoproteomics.

Click chemistry─specifically the copper-catalyzed azide-alkyne cycloaddition─has enabled the development of a wide range of chemical probes to analyze subsets of the functional proteome. The "clickable" proteome can be selectively enriched by using diverse cleavable biotin tags, but the direct identification of probe/tag-modified peptides (or peptide-centric analysis) remains challenging. Here, we evaluated the performance of five commercially available cleavable biotin tags in three most common chemoproteomic workflows, resulting in a comparative analysis of 15 methods. An acid-cleavable biotin tag with a dialkoxydiphenylsilane moiety, in combination with the protein "click", peptide "capture" workflow, outperforms all other methods in terms of enrichment efficiency, identification yield, and reproducibility, although its performance may be slightly compromised by the formation of an unwanted formate product revealed by blind search. Despite being inferior, photocleavable, and reduction-cleavable, biotin tags can also find their applicable sceneries, especially when dealing with acid-sensitive probes or probe-derived modifications. Furthermore, the systematic comparison of LC-MS/MS characteristics of tag-modified peptides provides valuable information for the future development of cleavable biotin reagents. Taken together, our data provides a much-needed practical guidance for researchers interested in developing and/or applying an ideal cleavable biotin tag to peptide-centric chemoproteomics.

Cloning and functional verification of a porcine adipose tissue-specific promoter.

BACKGROUND: Fat deposition is an important economic trait in pigs. In the past decades, many genes regulating porcine fat deposition were identified by Omics technology and verified by cell biology studies. Using genetically modified pigs to investigate the function of these genes in vivo is necessary before applying in breeding. However, lack of tissue-specific promoters of pigs hinders the generation of adipose tissue-specific genetically modified pigs. RESULTS: In order to identify a porcine adipose tissue-specific promoter, we used the software Digital Differential Display (DDD) to screen 99 genes highly expressed in porcine adipose tissue. GO and KEGG enrichment analysis indicated that the 99 genes were mainly related to lipid metabolism. Q-PCR proved that LGALS12 was an adipose tissue-specific gene. Five truncated fragments of the LGALS12 promoter were cloned and the 4 kb fragment (L-4 kb) exhibited a high level of promoter activity in adipocytes and no promoter activity in non-adipocytes. Following co-transfection with adipogenic transcription factors, the promoter activity of L-4 kb was enhanced by PPARγ, C/EBPß, and KLF15, whereas it was suppressed by KLF4. Finally, we demonstrated that L-4 kb can drive APOR gene expression to exert its function in adipocytes. CONCLUSIONS: This study demonstrates that porcine LGALS12 is an adipose tissue-specific gene, and identified the 4 kb fragment of LGALS12 promoter that exhibited adipocyte-specific promoter activity. These results provide new evidence for understanding porcine fat deposition and a promoter element for adipose tissue-specific genetic modification in pigs. HIGHLIGHTS: Identified porcine LGALS12 as an adipose tissue-specific gene. Truncated LGALS12 promoter (L-4 kb) showed adipose tissue-specific promoter activity. Identified transcription factors involved in the regulation of L-4 kb promoter activity.

The value of gadobenate dimeglumine-enhanced biliary imaging from the hepatobiliary phase for predicting post-hepatectomy liver failure in HCC patients.

OBJECTIVES: To determine the value of gadobenate dimeglumine-enhanced biliary imaging from the hepatobiliary phase for predicting post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). METHODS: Patients with HCC who underwent gadobenate dimeglumine-enhanced hepatobiliary magnetic resonance imaging prior to hepatectomy were collected in two centers. The relative enhancement ratio of the biliary system (REB) and the liver to muscle ratio (LMR) were measured at the hepatobiliary phase. Potential risk factors for PHLF were analyzed by logistic regression. The capacity of the REB and LMR to predict PHLF was analyzed via receiver operating characteristic curve. RESULTS: Of the 221 patients, post-hepatectomy liver failure occurred in 60 patients (27.1%). The REB was an independent risk factor for PHLF (odds ratio [OR] = 0.127 [0.047-0.348], p < 0.001). Although the LMR tended to be associated with PHLF (p = 0.063), it was not an independent risk factor in the multivariable analysis (OR = 0.624 [0.023-16.709], p = 0.779). Moreover, the area under the receiver operating characteristic curve of the REB and LMR was 0.87 and 0.60. The most appropriate cutoff value for the REB was 2.21. The HCC patients with the REB ≤ 2.21 had a higher incidence of post-hepatectomy liver failure than those with the REB > 2.21 (60.0% versus 8.5%, p < 0.001). CONCLUSIONS: Gadobenate dimeglumine-enhanced biliary imaging from the hepatobiliary phase was valuable in predicting post-hepatectomy liver failure in HCC patients. KEY POINTS: • The relative enhancement ratio of the biliary system (REB) was an independent risk factor for post-hepatectomy liver failure in HCC patients. • HCC patients with the REB ≤ 2.21 had significantly higher incidence of post-hepatectomy liver failure than those with the REB > 2.21 (60.0% versus 8.5%).

Gd-BOPTA-enhanced hepatobiliary phase MR imaging can predict the prognosis of patients with acute-on-chronic liver failure.

OBJECTIVES: To determine the value of gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging (MRI) from the hepatobiliary phase for predicting poor outcome in acute-on-chronic liver failure (ACLF) patients. METHODS: In this single-center retrospective study, 74 patients diagnosed as ACLF who underwent Gd-BOPTA-enhanced hepatobiliary magnetic resonance imaging were collected. The quantitative liver-spleen contrast ratio (Q-LSC) and the relative enhancement ratio of the biliary system (REB) at the hepatobiliary phase were measured. Cox proportional hazards regression models were used to evaluate prognostic factors. The capacity of the Q-LSC and REB to predict the 90-day outcome was evaluated via receiver operating characteristic (ROC) curve. RESULTS: During the follow-up period, twenty-eight of 74 ACLF patients (38%) had a poor outcome. The Q-LSC and REB were significant predictive factors (hazard ratio [HR] = 0.03 [0.002-0.54], p < 0.05; HR = 0.07 [0.01-0.88], p < 0.05) for prognosis in patients with ACLF. Moreover, the areas under the ROC curves of Q-LSC and REB for predicting poor outcome in patients with ACLF were 0.81 and 0.80, respectively. The most appropriate cutoff values for the Q-LSC and REB were 1.09 and 0.57, respectively. The ACLF patients with the Q-LSC ≤ 1.09 or REB ≤ 0.57 had a low cumulative survival. CONCLUSIONS: Gd-BOPTA-enhanced hepatobiliary phase MR imaging can predict poor outcome in patients with acute-on-chronic liver failure. KEY POINTS: • The quantitative liver-spleen contrast ratio at the hepatobiliary phase was a significant predictive prognostic factor in patients with acute-on-chronic liver failure. • The relative enhancement ratio of the biliary system at the hepatobiliary phase was a significant prognostic factor in patients with acute-on-chronic liver failure. • Gadobenate dimeglumine contrast-enhanced MR imaging from the hepatobiliary phase can predict poor outcome in patients with acute-on-chronic liver failure.

Nonalcoholic fatty liver disease, serum cytokines, and dementia among rural-dwelling older adults in China: A population-based study.

BACKGROUND AND PURPOSE: Little is known about whether nonalcoholic fatty liver disease (NAFLD) is associated with dementia or the role of serum proinflammatory cytokines in the association. We aimed to investigate the interrelationships of NAFLD, serum cytokines, and dementia among rural-dwelling older adults. METHODS: This population-based cross-sectional study included 5129 participants (aged ≥60 years; 61.79% women) who were living in rural communities and examined in March 2018-September 2018. NAFLD was defined through transabdominal ultrasound examination in the absence of hepatitis B or excessive alcohol consumption. Serum cytokines were measured in a subsample (n = 1686). Dementia, Alzheimer disease (AD), and vascular dementia (VaD) were diagnosed following international criteria. Data were analyzed with logistic regression and mediation models. RESULTS: Of the 5129 participants, 455 (8.87%) were detected with moderate-to-severe NAFLD, and 292 (5.69%) were diagnosed with dementia (188 with AD and 96 with VaD). The multivariable adjusted odds ratios associated with moderate-to-severe (vs. no-to-mild) NAFLD were 2.22 (95% confidence interval [CI] = 1.41-3.49) for all-cause dementia, 1.88 (95% CI = 1.01-3.50) for AD, and 2.62 (95% CI = 1.33-5.17) for VaD. In the cytokine subsample, controlling for multiple potential confounders, moderate-to-severe NAFLD was significantly associated with higher levels of serum monocyte chemotactic protein-1, interleukin-17A, interleukin-6 (IL-6), interleukin-8, and tumor necrosis factor-α (P < 0.05). The mediation analysis showed that IL-6 mediated 12.56% of the association between NAFLD and VaD. CONCLUSIONS: Moderate-to-severe nonalcoholic fatty liver disease is associated with dementia and AD, especially with VaD, among rural-dwelling Chinese older adults, in which the association with VaD is partly mediated by serum inflammatory cytokines.

Self-reported sleep characteristics associated with dementia among rural-dwelling Chinese older adults: a population-based study.

BACKGROUND: Sleep characteristics associated with dementia are poorly defined and whether their associations vary by demographics and APOE genotype among older adults are unclear. METHODS: This population-based cross-sectional study included 4742 participants (age ≥ 65 years, 57.1% women) living in rural China. Sleep parameters were measured using the self-rated questionnaires of the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, and the National Institute on Aging-Alzheimer's Association criteria for Alzheimer's disease (AD). Data were analysed using multiple logistic and general linear regression models. RESULTS: Dementia was diagnosed in 173 participants (115 with AD). Multivariable-adjusted odds ratio (OR) of dementia was 1.71 (95%CI, 1.07-2.72) for sleep duration ≤4 h/night (vs. > 6-8 h/night), 0.76 (0.49-1.18) for > 4-6 h/night, 1.63 (1.05-2.55) for > 8 h/night, 1.11 (1.03-1.20) for lower sleep efficiency (per 10% decrease), and 1.85 (1.19-2.89) for excessive daytime sleepiness. Very short sleep duration (≤4 h/night), lower sleep efficiency, and excessive daytime sleepiness were significantly associated with being diagnosed with AD (multivariable-adjusted OR range = 1.12-2.07; p < 0.05). The associations of sleep problems with dementia and AD were evident mainly among young-old adults (65-74 years) or APOE ε4 carriers. Among dementia-free participants, these sleep characteristics were significantly associated with a lower MMSE score. CONCLUSIONS: Self-reported sleep problems in dementia are characterized by very short or long sleep duration, low sleep efficiency, and excessive daytime sleepiness, especially among young-old people and APOE ε4 carriers. TRIAL REGISTRATION: ChiCTR1800017758 (Aug 13, 2018).

Climate-driven variation in mosquito density predicts the spatiotemporal dynamics of dengue.

Dengue is a climate-sensitive mosquito-borne disease with increasing geographic extent and human incidence. Although the climate-epidemic association and outbreak risks have been assessed using both statistical and mathematical models, local mosquito population dynamics have not been incorporated in a unified predictive framework. Here, we use mosquito surveillance data from 2005 to 2015 in China to integrate a generalized additive model of mosquito dynamics with a susceptible-infected-recovered (SIR) compartmental model of viral transmission to establish a predictive model linking climate and seasonal dengue risk. The findings illustrate that spatiotemporal dynamics of dengue are predictable from the local vector dynamics, which in turn, can be predicted by climate conditions. On the basis of the similar epidemiology and transmission cycles, we believe that this integrated approach and the finer mosquito surveillance data provide a framework that can be extended to predict outbreak risk of other mosquito-borne diseases as well as project dengue risk maps for future climate scenarios.

Mining for protein S-sulfenylation in Arabidopsis uncovers redox-sensitive sites.

Hydrogen peroxide (H2O2) is an important messenger molecule for diverse cellular processes. H2O2 oxidizes proteinaceous cysteinyl thiols to sulfenic acid, also known as S-sulfenylation, thereby affecting the protein conformation and functionality. Although many proteins have been identified as S-sulfenylation targets in plants, site-specific mapping and quantification remain largely unexplored. By means of a peptide-centric chemoproteomics approach, we mapped 1,537 S-sulfenylated sites on more than 1,000 proteins in Arabidopsis thaliana cells. Proteins involved in RNA homeostasis and metabolism were identified as hotspots for S-sulfenylation. Moreover, S-sulfenylation frequently occurred on cysteines located at catalytic sites of enzymes or on cysteines involved in metal binding, hinting at a direct mode of action for redox regulation. Comparison of human and Arabidopsis S-sulfenylation datasets provided 155 conserved S-sulfenylated cysteines, including Cys181 of the Arabidopsis MITOGEN-ACTIVATED PROTEIN KINASE4 (AtMAPK4) that corresponds to Cys161 in the human MAPK1, which has been identified previously as being S-sulfenylated. We show that, by replacing Cys181 of recombinant AtMAPK4 by a redox-insensitive serine residue, the kinase activity decreased, indicating the importance of this noncatalytic cysteine for the kinase mechanism. Altogether, we quantitatively mapped the S-sulfenylated cysteines in Arabidopsis cells under H2O2 stress and thereby generated a comprehensive view on the S-sulfenylation landscape that will facilitate downstream plant redox studies.

High-Performance Thermoelectric α-Ag9 Ga1-x Te6 Compounds with Ultralow Lattice Thermal Conductivity Originating from Ag9 Te2 Motifs.

We have determined the complex atomic structure of high-temperature α-Ag9 GaTe6 phase with a hexagonal lattice (P63 mc space group, a=b=8.2766 Å, c=13.4349 Å). The structure has outer [GaTe4 ]5- tetrahedrons and inner [Ag9 Te2 ]5+ clusters. All of the Ag ions are disorderly distributed in the lattice. Seven types of the Ag atoms constitute the cage-like [Ag9 Te2 ]5+ clusters. The highly disordered Ag ions vibrate in-harmonically, producing strong coupling between low frequency optical phonons and acoustic phonons. This in conjunction with a low sound velocity of 1354 m s-1 leads to an ultralow thermal conductivity of 0.20 W m-1 K-1 at 673 K. Meanwhile, the deficiency of Ga in Ag9 Ga1-x Te6 compounds effectively optimizes the electronic transport properties. Ag9 Ga0.91 Te6 attains a highest power factor of 0.40 mW m-1 K-2 at 673 K. All these contribute to a much-improved ZT value of 1.13 at 623 K for Ag9 Ga0.95 Te6 , which is 41 % higher than that of the pristine Ag9 GaTe6 sample.

The co-expression of genes involved in seed coat and endosperm development promotes seed abortion in grapevine.

MAIN CONCLUSION: The seed coat gene VviAGL11 coordinates with endosperm development genes FIS2, PHERESE1 and IKU2 and functions as the key regulator in seed development and abortion processes in grapevine. Seed development is essential for the reproduction of flowering plants. Seed abortion is a specific characteristic that produces seedless berries and is often observed in cultivated grapevines. Although seedlessness is an important trait for table and dried grapevine production, the mechanism of seed abortion remains poorly understood. This research aimed to analyze the co-expression of the seed coat development gene VviAGL11 and the endosperm development genes FERTILIZATION INDEPENDENT SEED2 (FIS2), PHERESE1 and HAIKU2 (IKU2) that regulate seedless fruit development in grapevine. The transcript levels of VviAGL11, FIS2, PHERESE1 and IKU2 all decreased during seed abortion in the seedless grape 'Thompson Seedless' plants, compared to those of the seeded grape 'Pinot Noir'. The transcript levels of the salicylic acid (SA)-dependent defense response genes EDS1, NPR1, NDR1 and SID2 were higher in 'Thompson Seedless' than 'Pinot Noir' during seed development. Also, WRKY3, WRKY6 and WRKY52, which participate in the SA pathway, were higher expressed in 'Thompson Seedless' than in 'Pinot Noir', indicating that SA-dependent defense responses may regulate seed abortion. The genes related to synthesis and metabolism of gibberellic acid (GA) and abscisic acid (ABA) also showed differential expression between 'Thompson Seedless' and 'Pinot Noir'. Exogenous applications of plant growth regulators (PGRs) to inflorescences of three stenospermocarpy grapevines before flowering showed that GA3 was critical prominently in seed development. Therefore, the co-expression of seed coat and endosperm development-related genes, SA pathway genes, and genes for the synthesis and metabolism of GA3 together enhance seed abortion in seedless grapes.

Prognostic value of the extent of lymphadenectomy for esophageal cancer-specific survival among T1 patients.

BACKGROUND: Clinically, there are no clear guidelines on the extent of lymphadenectomy in patients with T1 esophageal cancer. Studying the minimum number of lymph nodes for resection may increase cancer-specific survival. METHODS: Patients who underwent esophagectomy and lymphadenectomy at T1 stage were selected from the Surveillance, Epidemiology and End Results Program (United States, 1998-2014). Maximally selected rank and Cox proportional hazard models were used to examine three variables: the number of lymph nodes examined, the number of negative lymph nodes and the lymph node ratio. RESULTS: Approximately 18% had lymph node metastases, where the median values were 10, 10 and 0 for the number of lymph nodes examined, the number of negative lymph nodes and the lymph node ratio, respectively. All three examined variables were statistically associated with cancer-specific survival probability. Dividing patients into two groups shows a clear difference in cancer-specific survival compared to four or five groups for all three variables: there was a 29% decrease in the risk of death with the number of lymph nodes examined ≥14 vs < 14 (hazard ratio 0.71, 95% confidence interval: 0.57-0.89), a 35% decrease in the risk of death with the number of negative lymph nodes ≥13 vs < 13 (hazard ratio 0.65, 95% confidence interval: 0.52-0.81), and an increase of 1.21 times in the risk of death (hazard ratio 2.21, 95% confidence interval: 1.76-2.77) for the lymph node ratio > 0.05 vs ≤ 0.05. CONCLUSIONS: The extent of lymph node dissection is associated with cancer-specific survival, and the minimum number of lymph nodes that need to be removed is 14. The number of negative lymph nodes and the lymph node ratio also have prognostic value after lymphadenectomy among T1 stage patients.

Gadobenate dimeglumine-enhanced biliary imaging from the hepatobiliary phase can predict progression in patients with liver cirrhosis.

OBJECTIVES: To determine the value of gadobenate dimeglumine (Gd-BOPTA)-enhanced biliary imaging from the hepatobiliary phase in predicting hepatic decompensation and insufficiency for patients with cirrhosis. METHODS: This single-center retrospective study included 270 patients who underwent Gd-BOPTA-enhanced magnetic resonance imaging. The relative enhancement ratios of the biliary system (REB) and liver parenchyma (REL) in patients with normal liver function without underlying chronic liver disease and three groups of patients with Child-Pugh A, Child-Pugh B, and Child-Pugh C disease were measured. After a mean follow-up of 38.5 ± 22.5 months, prognostic factors were evaluated using the Cox proportional hazards regression model. Receiver operating characteristic (ROC) curve analyses were performed to assess the capacity of the REB and REL to predict the development of hepatic decompensation and insufficiency. RESULTS: During the follow-up period, nine of 79 patients with Child-Pugh A disease developed hepatic decompensation. The REB was a significant predictive factor (hazard ratio (HR) = 0.40 (0.19-0.84); p = 0.016), but the REL showed no association with hepatic decompensation. Moreover, the areas under the ROC curves (AUCs) were 0.83 and 0.52 for the REB and REL, respectively. Thirty-eight of 207 patients with cirrhosis developed hepatic insufficiency. The REB was a significant predictive factor (HR = 0.24 (0.13-0.46); p < 0.0001), but the REL did not show statistically significant association with hepatic insufficiency. The AUCs were 0.82 and 0.57 for the REB and REL, respectively. CONCLUSIONS: Gd-BOPTA-enhanced biliary imaging from the hepatobiliary phase was valuable in predicting hepatic decompensation and insufficiency for cirrhotic patients. KEY POINTS: • Gd-BOPTA-enhanced biliary imaging was a significant predictive factor for hepatic decompensation in patients with cirrhosis. • Gd-BOPTA-enhanced biliary imaging was a significant predictive factor for hepatic insufficiency in patients with cirrhosis. • Gd-BOPTA-enhanced biliary imaging showed superior predictive values for adverse clinical outcomes compared to liver parenchymal imaging at the hepatobiliary phase.