Search

The enzyme DWARF27 (D27) catalyzes the reversible isomerization of all-trans- into 9-cis-β-carotene, initiating strigolactone (SL) biosynthesis. Genomes of higher plants encode two D27-homologs, D27-like1 and -like2, with unknown functions. Here, we investigated the enzymatic activity and biological function of the Arabidopsis D27-like1. In vitro enzymatic assays and expression in Synechocystis sp. PCC6803 revealed a yet not reported 13-cis/15-cis/9-cis- and a 9-cis/all-trans-β-carotene isomerization. Although disruption of AtD27-like1 did not cause SL deficiency phenotypes, overexpression of AtD27-like1 in the d27 mutant restored the more-branching phenotype, indicating a contribution of AtD27-like1 to SL biosynthesis. Accordingly, generated d27 d27like1 double mutants showed more pronounced branching phenotype, compared to d27. The contribution of AtD27-like1 to SL biosynthesis is likely due to its formation of 9-cis-β-carotene that was present at higher levels in AtD27-like1 overexpressing lines. In contrast, AtD27-like1 expression correlated negatively with the content of 9-cis-violaxanthin, a precursor of abscisic acid (ABA), in shoots. Consistently, ABA levels were higher in shoots and also in dry seeds of the d27like1 and d27 d27like1 mutants. Transgenic lines expressing β-glucuronidase (GUS) driven by the AtD27LIKE1 promoter and transcript analysis of hormone-treated Arabidopsis seedlings unraveled that AtD27LIKE1 is expressed in different tissues and regulated ABA and auxin. Taken together, our work revealed a cis/cis-β-carotene isomerase that affects the content of both cis-carotenoid derived plant hormones ABA and SLs.

Global pincer is a relatively rare form of pincer deformity and is typically associated with technical challenges during surgery. So far, controversy remains whether patients with global pincer have equivalent surgical outcomes compared to patients with focal pincer. This study compares the clinical outcomes of arthroscopic treatment between patients with global pincer femoroacetabular impingement (FAI) and focal pincer FAI in the Chinese population.Data were retrospectively collected from patients with global and focal pincer FAI who underwent hip arthroscopy with a minimum two-year follow-up between April 2016 and December 2018. Radiographic measurements, arthroscopic procedures, preoperative and postoperative patient-reported outcomes (PROs) including modified Harris hip score (mHHS), hip outcome score-activities of daily living (HOS-ADL), international hip outcome tool-12 (iHOT-12), and visual analogue scale (VAS) scores, rates of revision surgery and conversion to total hip arthroplasty (THA) were recorded. Achievement of minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) was compared for the VAS, mHHS, HOS-ADL, and iHOT-12 scores between groups.The total of 33 and 167 patients were included in the global and focal group, respectively. There were no intergroup differences in age, gender, body mass index or follow-up times. Lateral center-edge angle (LCEA) was reduced in both groups postoperatively. Both groups demonstrated significant improvements in PROs compared with preoperative levels at the final follow-up. The preoperative scores showed significant differences in terms of mHHS (60.34 vs 62.90, P = 0.031) and HOS-ADL (61.45 vs 64.74, P = 0.022) scores between two groups, and the improvement of HOS-ADL score was significantly higher in global group (P = 0.027). However, the postoperative scores, including VAS, mHHS, HOS-ADL, and iHOT-12 scores, showed no significant differences between two groups. And there were no significant differences in the rate of meeting the PASS and MCID between groups. One (3.0%) in the global group and six (3.6%) patients in the focal group underwent revision arthroscopy respectively, with no significant difference (P = 0.876). There were no conversions to THA in both groups.Arthroscopic management of global pincer FAI can achieve excellent functional scores at minimum 2-year follow-up. The outcomes were similar to focal pincer FAI patients with a low rate of secondary procedure.

The endothelial-mesenchymal transition (EndMT) is an important mechanism in tissue regeneration and the development of organ fibrosis. Whether EndMT occurs in wound healing and scarring remains unknown.The isolated cells from the normal dermal tissue and the wound tissue of mouse with full-thickness skin wound, and human scar tissue sections were performed with CD31/factorVII and α-SMA immunohistochemical staining and H and E staining. The ratio of factor VII or CD31/α-SMA double-positive cells in factor VII-positive cells was assessed in the isolated cells and in scar tissues.In this study, we found that approximately 27-60% of ECs coexpressed VII factor and α-SMA in the isolated cells from the wound tissues of mice, which was significantly higher than that of normal dermal tissue cells. Accordingly, the number of CD31/α-SMA double-positive cells in mouse wound tissue sections was also significantly more than that in normal dermal tissue sections. In scar tissues, in addition to high-density microvessels, a large number of proliferative ECs in scar strama and CD31/α-SMA double-positive cells were also found. Approximately 46.82 to 84.11% of ECs and 68.77 to 95.25% of myofibroblasts coexpressed VII factor and α-SMA, and these two values in hypertrophic scars were significantly higher than those in keloids.These results confirmed that ECs might contribute to the emergence of myofibroblasts in the wound and scar tissue via the process of EndMT.

The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility.The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD.A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification.In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively.Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.

The objective of this study was to update the association between multivitamin supplementation and total or cause-specific mortality in a population with a high prevalence of undernutrition in China.The Linxian Dysplasia Nutrition Intervention Trial was a randomized, double-blind, placebo-controlled trial in which 3318 persons aged 40-69 years with esophageal squamous dysplasia were assigned to receive daily multivitamin supplementation or a placebo for 6 years and were followed for 29 years. The primary outcome was esophageal/gastric cardia cancer mortality. The data were analyzed with Cox proportional hazards regression models. Subgroup analyses were performed by common characteristics such as age and gender.The cumulative total mortality was 83.5%. Multivitamin supplementation did not affect total or cause-specific mortality in the participants as a whole (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.89-1.03). Subgroup analyses showed that no association between multivitamin supplementation and all-cause mortality was observed in men (HR, 0.90; 95% CI, 0.81-1.01), women (HR, 1.01; 95% CI, 0.91-1.12), younger participants (HR, 0.97; 95% CI, 0.87-1.08), or older participants (HR, 0.94; 95% CI, 0.85-1.04). Significant reductions in heart disease mortality (HR, 0.64; 95% CI, 0.47-0.87) and cerebrovascular disease mortality (HR, 0.74; 95% CI, 0.56-1.00) were seen in older men. In a subgroup of younger men and a subgroup of moderate or severe dysplasia, subjects receiving multivitamin supplementation had a lower risk of esophageal/cardia cancer mortality (HR for younger men, 0.76; 95% CI, 0.58-0.99; HR for moderate or severe dysplasia, 0.76; 95% CI, 0.58-1.00). No association between multivitamin supplementation and any cause-specific mortality was observed in a mild dysplasia population.Multivitamin supplementation in a population with esophageal squamous dysplasia was not associated with the risk of total mortality in the 35-year follow-up of this randomized controlled trial. In light of this and previous trials, multivitamin supplements should be used thoughtfully to improve health status of populations with esophageal squamous dysplasia.Multivitamin supplementation is common, yet its effect on mortality is unclear. The aim of this study was to update the long-term effects of multivitamin supplementation on total and cause-specific mortality during nearly 35 years of follow-up in the Linxian Dysplasia Nutrition Intervention Trial in China. Multivitamin supplementation in a population with esophageal squamous dysplasia was not associated with the risk of total mortality in the 35-year follow-up of this randomized controlled trial, and this indicates that multivitamin supplements should be used thoughtfully to improve health status.

Alagille syndrome (ALGS) type 2 caused by mutations in NOTCH2 has genotypic and phenotypic heterogeneity. Diagnosis in some atypical patients with isolated hepatic presentation could be missed.Using 2087 patients with paediatric liver manifestations, NOTCH2 allele frequencies, in-silico prediction, protein domains and clinical features were analysed to define the pathogenicity of NOTCH2 variants for diagnosis of ALGS type 2.Among 2087 patients with paediatric liver manifestations, significantly more NOTCH2 variants were absent in gnomAD in patients with elevated γ-glutamyltransferase (GGT) (p = .041). Significantly more NOTCH2 variants which were absent in gnomAD were located in protein functional domains (p = .038). When missense variants were absent in gnomAD and predicted to be pathogenic by at least three out of seven in-silico tools, they were found to be significantly associated with liver manifestations with elevated GGT (p = .003). Comparing this to patients with likely benign (LB) variants, the patients with likely-pathogenic (LP) variants have significantly more liver manifestations with elevated GGT (p = .0001). Significantly more patients with LP variants had extra-hepatic phenotypes of ALGS compared with those patients with LB variants (p = .0004).When NOTCH2 variants are absent in gnomAD, null variants and missense variants which were predicted to be pathogenic by at least three in-silico tools could be considered pathogenic in patients with high GGT chronic liver diseases.

The main objective of the study was to evaluate the bioequivalence of two rosuvastatin calcium tablets in healthy Chinese subjects under fasted and fed conditions. The study was carried out using a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design, with a washout period of 7 days. Both the fasted study and fed study enrolled 28 subjects. In each study period, the subjects were administrated a single oral dose of the test product or reference product of rosuvastatin 10 mg. Blood samples were collected from pre-dose to 72 hours after administration with 16 time points in total. Bioequivalence evaluation was performed using ln-transformed pharmacokinetic parameters of rosuvastatin, including C

As a promising alternative to the mainstream CoFeB/MgO system with interfacial perpendicular magnetic anisotropy (PMA), L1(0)-FePd and its synthetic antiferromagnet (SAF) structure with large crystalline PMA can support spintronic devices with sufficient thermal stability at sub-5 nm sizes. However, the compatibility requirement of preparing L1(0)-FePd thin films on Si/SiO(2) wafers is still unmet. In this paper, we prepare high-quality L1(0)-FePd and its SAF on Si/SiO(2) wafers by coating the amorphous SiO(2) surface with an MgO(001) seed layer. The prepared L1(0)-FePd single layer and SAF stack are highly (001)-textured, showing strong PMA, low damping, and sizeable interlayer exchange coupling, respectively. Systematic characterizations, including advanced X-ray diffraction measurement and atomic resolution-scanning transmission electron microscopy, are conducted to explain the outstanding performance of L1(0)-FePd layers. A fully-epitaxial growth that starts from MgO seed layer, induces the (001) texture of L1(0)-FePd, and extends through the SAF spacer is observed. This study makes the vision of scalable spintronics more practical.

Applying the emerging molecular networking strategy, an uncommon cembranoid orthoester, sarcotortin A (1), featuring a 3/14/8/5-fused scaffold, an unusual eunicellane-type diterpenoid, sarcotorolide A (2), and two new biscembranoids, ximaolides M and N (7 and 8), along with nine known terpenoids 3-6 and 9-13 were isolated from the Hainan soft coral Sarcophyton tortuosum. The structure and absolute configuration of all new compounds were established by a combination of spectroscopic data, X-ray diffraction analysis, and/or quantum chemical computational approaches. The plausible biogenetic relationship among these skeletally different terpenoids was proposed and discussed. In in vitro bioassay, new compound 7 exhibited a remarkable inhibitory activity against protein tyrosine phosphatases 1B (PTP1B) with the IC50 value of 8.06 μM. In addition, compounds 4 and 10 displayed significant inhibitory effects on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages cells with the IC50 values of 19.13 and 16.45 μM, respectively. Compound 9 showed interesting cytotoxicity against H1975, MDA-MB231, A549, and H1299 cancer cell lines with IC50 values of 31.59, 34.96, 43.87, and 27.93 μM, respectively.

Non-alcoholic fatty liver disease (NAFLD) is a major health problem in Western countries and has become the most common cause of chronic liver disease. Although NAFLD is closely associated with obesity, inflammation, and insulin resistance, its pathogenesis remains unclear. The disease begins with excessive accumulation of triglycerides in the liver, which in turn leads to liver cell damage, steatosis, inflammation, and so on. P38γ is one of the four isoforms of P38 mitogen-activated protein kinases (P38 MAPKs) that contributes to inflammation in different diseases. In this research, we investigated the role of P38γ in NAFLD. In vivo, a NAFLD model was established by feeding C57BL/6J mice with a methionine- and choline-deficient (MCD) diet and adeno-associated virus (AAV9-shRNA-P38γ) was injected into C57BL/6J mice by tail vein for knockdown P38γ. The results indicated that the expression level of P38γ was upregulated in MCD-fed mice. Furthermore, the downregulation of P38γ significantly attenuated liver injury and lipid accumulation in mice. In vitro, mouse hepatocytes AML-12 were treated with free fatty acid (FFA). We found that P38γ was obviously increased in FFA-treated AML-12 cells, whereas knockdown of P38γ significantly suppressed lipid accumulation in FFA-treated AML-12 cells. Furthermore, P38γ regulated the Janus Kinase-Signal transducers and activators of transcription (JAK-STAT) signaling pathway. Inhibition of P38γ can inhibit the JAK-STAT signaling pathway, thereby inhibiting lipid accumulation in FFA-treated AML-12 cells. In conclusion, our results suggest that targeting P38γ contributes to the suppression of lipid accumulation in fatty liver disease.

Surface terminations of two-dimensional MXene (Ti3 C2 Tx ) considerably impact its physicochemical properties. Commonly used etching methods usually introduce -F surface terminations or metallic impurities in MXene. We present a new molten-salt-assisted electrochemical etching method to synthesize fluorine-free Ti3 C2 Cl2 . Using electrons as reaction agents, cathode reduction and anode etching can be spatially isolated; thus, no metallics are present in the Ti3 C2 Cl2 product. The surface terminations can be in situ modified from -Cl to -O and/or -S, which considerably shortens the modification steps and enriches the variety of surface terminations. The obtained -O-terminated Ti3 C2 Tx are excellent electrode materials for supercapacitors, exhibiting capacitances of 225 F g-1 at 1.0 Ag-1 , good rate performance (91.1 % at 10 Ag-1 ), and excellent capacitance retention (100 % after 10000 charge/discharge cycles at 10 Ag-1 ), which is superior to multi-layered Ti3 C2 Tx prepared by other etching methods.

Background Dyslipidemia International Study II (DYSIS II)‐China was conducted to determine the low‐density lipoprotein cholesterol (LDL‐C) goal (

Residue hepatocellular carcinoma (HCC) cells enduring hypoxic environment triggered by interventional embolization obtain more malignant potential with little clarified mechanism. The N6‐methyladenosine (m6A) biological activity plays essential roles in diverse physiological processes. However, its role under hypoxic condition remains largely unexplored. RT‐qPCR and Western blot were used to evaluate METTL14 expression in hypoxic HCC cells. MDA assay and electronic microscopy photography were used to evaluate ferroptosis. The correlation between SLC7A11 and METTL14 was conducted by bioinformatical analysis. Flow cytometry was used to verify the effect of SLC7A11 on ROS production. Cell counting kit‐8 assay was performed to detect cells proliferation ability. Hypoxia triggered suppression of METTL14 in a HIF‐1α–dependent manner potently abrogated ferroptosis of HCC cells. Mechanistic investigation identified SLC7A11 was a direct target of METTL14. Both in vitro and in vivo assay demonstrated that METTL14 induced m6A modification at 5’UTR of SLC7A11 mRNA, which in turn underwent degradation relied on the YTHDF2‐dependent pathway. Importantly, ectopic expression of SLC7A11 strongly blocked METTL14‐induced tumour‐suppressive effect in hypoxic HCC. Our investigations lay the emphasis on the hypoxia‐regulated ferroptosis in HCC cells and identify the HIF‐1α /METTL14/YTHDF2/SLC7A11 axis as a potential therapeutic target for the HCC interventional embolization treatment.

Platelets may serve as a perfect peripheral source for exploring diagnostic biomarkers for Alzheimer's disease (AD); however, the molecular linkage between platelet and the brain is missing. To find the common altered and driving molecules in both brain and the platelet, we performed an integrated analysis of our platelet omics and brain omics reported in the literature, and analyzed their correlations with AD-specific pathology and cognitive impairment. By integrating the gene and protein expression profiles from 269 AD patients, we deduced 239 differentially expressed proteins (DEPs) appeared in both brain and the platelet, and 70.3% of them had consistent changes. Further analysis demonstrated that the altered brain and peripheral regulations were pinpointed into 10 imbalanced pathways. We also found that 117 DEPs, including ADAM10, were closely associated to the AD-specific β-amyloid and tau pathologies; and the changes of IDH3B and RTN1 had a potential diagnostic value for cognitive impairment analyzed by machine learning. Finally, we identified that HMOX2 and SERPINA3 could serve as driving molecules in neurodegeneration, and they were increased and decreased in AD patients, respectively. Together, this integrated brain and platelet omics provides a valuable resource for establishing efficient peripheral diagnostic biomarkers and potential therapeutic targets for AD.

A palladium supported on graphitic carbon nitride (Pd/g-C3 N4 ) catalyzed carbonylative reaction of aryl bromides and arylboronic acids by has been developed for the construction of diaryl ketones. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source, the reaction proceeded well to give various diaryl ketones in moderate to good yields.

Dry reforming of methane (DRM) is a feasible solution to cope with the reduction of greenhouse gas under the Paris Convention's obligations, given that it adds value by converting trivial gases of CO2 and CH4 simultaneously into useful syngas. However, conventional Ni catalyst undergoes deactivation due to carbon coking and particle agglomeration. Here we demonstrate for the first time a highly efficient and durable DRM catalyst of exsolved Co-Ni-Fe ternary alloy nanoparticles on the layered perovskite PrBaMn1.7Co0.1Ni0.2O5+d produced by topotactic exsolution. This readily allows the generation of a larger number of exsolved nanoparticles, enhancing catalytic activity above those of Ni monometallic and Co-Ni bimetallic particles. The enhancement is achieved by the optimal up-shift of the d-band center of Co-Ni-Fe than those of Co-Ni and Ni meaning easier charge donation to the adsorbate. Furthermore, the exsolved catalyst shows exceptional stability with the continuous DRM operation for about 350 hours.