Aim
Genome‐wide association studies (GWAS) have identified multiple susceptibility loci associated with insulin resistance (IR)‐relevant phenotypes. However, the genes responsible for these ...associations remain largely unknown. We aim to identify susceptibility genes for IR‐relevant phenotypes via a transcriptome‐wide association study.
Materials and Methods
We conducted a large‐scale multi‐tissue transcriptome‐wide association study for IR (Insulin Sensitivity Index, homeostasis model assessment‐IR, fasting insulin) and lipid‐relevant traits (high‐density lipoprotein cholesterol, triglycerides, low‐density lipoprotein cholesterol and total cholesterol) using the largest GWAS summary statistics and precomputed gene expression weights of 49 human tissues. Conditional and joint analyses were implemented to identify significantly independent genes. Furthermore, we estimated the causal effects of independent genes by Mendelian randomization causal inference analysis.
Results
We identified 1190 susceptibility genes causally associated with IR‐relevant phenotypes, including 58 genes that were not implicated in the original GWAS. Among them, 11 genes were further supported in differential expression analyses or a gene knockout mice database, such as KRIT1 showed both significantly differential expression and IR‐related phenotypic effects in knockout mice. Meanwhile, seven proteins encoded by susceptibility genes were targeted by clinically approved drugs, and three of these genes (H6PD, CACNB2 and DRD2) have been served as drug targets for IR‐related diseases/traits. Moreover, drug repurposing analysis identified four compounds with profiles opposing the expression of genes associated with IR risk.
Conclusions
Our study provided new insights into IR aetiology and avenues for therapeutic development.
Among numerous severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants of concerns, Omicron is more infectious and immune‐escaping, while Delta is more pathogenic. Here, we provide ...evidence for both intervariant and intravariant recombination of the rapidly evolving new SARS‐CoV‐2 genomes, including XD/XE/XF and BA.3, raising concerns of potential more infectious, immune‐escaping, and disease‐causing Omicron and Delta–Omicron variants.
Background
Computed tomography (CT) and magnetic resonance imaging (MRI) are both capable of predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). However, which modality is ...better is unknown.
Purpose
To intraindividually compare CT and MRI for predicting MVI in solitary HCC and investigate the added value of radiomics analyses.
Study Type
Retrospective.
Subjects
Included were 402 consecutive patients with HCC (training set:validation set = 300:102).
Field Strength/Sequence
T2‐weighted, diffusion‐weighted, and contrast‐enhanced T1‐weighted imaging MRI at 3.0T and contrast‐enhanced CT.
Assessment
CT‐ and MR‐based radiomics signatures (RS) were constructed using the least absolute shrinkage and selection operator regression. CT‐ and MR‐based radiologic (R) and radiologic‐radiomics (RR) models were developed by univariate and multivariate logistic regression. The performance of the RS/models was compared between two modalities. To investigate the added value of RS, the performance of the R models was compared with the RR models in HCC of all sizes and 2–5 cm in size.
Statistical Tests
Model performance was quantified by the area under the receiver operating characteristic curve (AUC) and compared using the Delong test.
Results
Histopathologic MVI was identified in 161 patients (training set:validation set = 130:31). MRI‐based RS/models tended to have a marginally higher AUC than CT‐based RS/models (AUCs of CT vs. MRI, P: RS, 0.801 vs. 0.804, 0.96; R model, 0.809 vs. 0.832, 0.09; RR model, 0.835 vs. 0.872, 0.54). The improvement of RR models over R models in all sizes was not significant (P = 0.21 at CT and 0.09 at MRI), whereas the improvement in 2–5 cm was significant at MRI (P < 0.05) but not at CT (P = 0.16).
Data Conclusion
CT and MRI had a comparable predictive performance for MVI in solitary HCC. The RS of MRI only had significant added value for predicting MVI in HCC of 2–5 cm.
Level of Evidence
3
Technical Efficacy
Stage 2
The first asymmetric catalytic approach to multilayer 3D chirality has been achieved by using Suzuki‐Miyaura cross‐couplings. New chiral catalysts were designed and screened under various catalytic ...systems that proved chiral amide‐phosphines to be more efficient ligands than other candidates. The multilayer 3D framework was unambiguously determined by X‐ray structural analysis showing a parallel pattern of three layers consisting of top, middle and bottom aromatic rings. The X‐ray structure of a catalyst complex, dichloride complex of Pd‐phosphine amide, was obtained revealing an interesting asymmetric environment nearby the Pd metal center. Three rings of multilayer 3D products can be readily changed by varying aromatic ring‐anchored starting materials. The resulting multilayer products displayed strong luminescence under UV irradiation and strong aggregation‐induced emission (AIE). In the future, this work would benefit not only the field of asymmetric synthesis but also materials science, in particular polarized organic electronics, optoelectronics and photovoltaics.
The first asymmetric catalytic approach to multilayer 3D chirality by using Suzuki‐Miyaura cross‐couplings in the presence of new chiral amide‐phosphines is reported. The resulting multilayer products showed strong luminescence under UV irradiation, and displayed strong aggregation‐induced emission (AIE).
Renal fibrosis is considered as the pathway of almost all kinds of chronic kidney diseases (CKD) to the end stage of renal diseases (ESRD). Ganoderic acid (GA) is a group of lanostane triterpenes ...isolated from Ganoderma lucidum, which has shown a variety of pharmacological activities. In this study we investigated whether GA exerted antirenal fibrosis effect in a unilateral ureteral obstruction (UUO) mouse model. After UUO surgery, the mice were treated with GA (3.125, 12.5, and 50 mg· kg
·d
, ip) for 7 or 14 days. Then the mice were sacrificed for collecting blood and kidneys. We showed that GA treatment dose-dependently attenuated UUO-induced tubular injury and renal fibrosis; GA (50 mg· kg
·d
) significantly ameliorated renal disfunction during fibrosis progression. We further revealed that GA treatment inhibited the extracellular matrix (ECM) deposition in the kidney by suppressing the expression of fibronectin, mainly through hindering the over activation of TGF-β/Smad signaling. On the other hand, GA treatment significantly decreased the expression of mesenchymal cell markers alpha-smooth muscle actin (α-SMA) and vimentin, and upregulated E-cadherin expression in the kidney, suggesting the suppression of tubular epithelial-mesenchymal transition (EMT) partially via inhibiting both TGF-β/Smad and MAPK (ERK, JNK, p38) signaling pathways. The inhibitory effects of GA on TGF-β/Smad and MAPK signaling pathways were confirmed in TGF-β1-stimulated HK-2 cell model. GA-A, a GA monomer, was identified as a potent inhibitor on renal fibrosis in vitro. These data demonstrate that GA or GA-A might be developed as a potential therapeutic agent in the treatment of renal fibrosis.
spp. and its secondary metabolites have been widely applied in foods and medicines for thousands of years in eastern Asia. Nitrogen sources are essential nutrients for the growth and metabolism of
...spp. Our previous study found that inorganic nitrogen sources (especially NH
Cl and NH
NO
) promoted the biosynthesis of
pigments (MPs) and inhibited the production of citrinin. The objective of the present study was to investigate the regulatory mechanism of inorganic nitrogen on the biosynthesis of MPs and citrinin by the comparative transcriptional approach (RNA sequencing combined with RT-qPCR). Results indicated that the submerged fermentation of
M3103 with NH
Cl or NH
NO
as the sole nitrogen source can significantly increase the yields of MPs (especially for
orange and red pigments) and decrease citrinin production, compared with the organic nitrogen source (peptone group). Comparative transcriptomic profiling by RNA sequencing found that the numbers of differentially expressed genes (DEGs) between different experimental groups-M group (peptone group)
ML group (NH
Cl group), and M group (peptone group)
MX group (NH
NO
group), were 722 and 1287, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that genes involved in carbon and nitrogen metabolism, biosynthesis of amino acids were up-regulated by NH
Cl and NH
NO
, which would produce more biosynthetic precursors for MPs. Whereas, the inorganic nitrogen source (both of NH
Cl and NH
NO
) down-regulated the expression levels of genes involved in tyrosine metabolism. In addition, NR analysis indicated that the essential genes and transcription factors involved in the biosynthesis pathway of citrinin were down-regulated by NH
Cl and NH
NO
. These results indicated that NH
Cl or NH
NO
as a nitrogen source for
M3103 can significantly promote the precursor synthesis of
pigments, but reduce the transcription of polyketide synthase for citrinin, and therefore significantly increase
pigments production and decrease citrinin formation. These findings will facilitate a comprehensive understanding of the regulatory mechanisms of inorganic nitrogen in the biosynthesis of secondary metabolites in
, and would benefit the application of
in the production of MPs.
Metabolic associated fatty liver disease (MAFLD) is a new definition for liver disease associated with known metabolic dysfunction. Based on new diagnostic criteria, we aimed to investigate its ...prevalence and risk factors in Chinese population.
We conducted this study in a health examination population who underwent abdominal ultrasonography in China. The diagnosis of MAFLD was based on the new diagnostic criteria. The characteristics of the MAFLD population, as well as the associations between MAFLD and metabolic abnormalities, were explored. Mann-Whitney U test and chi-square test were performed to compare different variables. Binary logistic regression was used to determine the risk factors for MAFLD.
Among 139,170 subjects, the prevalence of MAFLD was 26.1% (males: 35.4%; females: 14.1%). The prevalence based on female menopausal status, that is, premenopausal, perimenopausal, and postmenopausal, was 6.1%, 16.8%, and 30.2%, respectively. In different BMI groups (underweight, normal, overweight and obese), the prevalence was 0.1%, 4.0%, 27.4% and 59.8%, respectively. The proportions of abnormal metabolic features in the MAFLD group were significantly higher than those in the non-MAFLD group, as was the proportion of elevated alanine aminotransferase (ALT) (42.5% vs. 11%, P < 0.001). In nonobese individuals with MAFLD, the proportions of abnormal metabolic features were also all significantly higher than those in nonobese individuals without MAFLD. The prevalence of metabolic syndrome (MS), dyslipidaemia, and hyperuricaemia, respectively, in the MAFLD group (53.2%, 80.0%, and 45.0%) was significantly higher than that in the non-MAFLD group (10.1%, 41.7%, and 16.8%). Logistic regression revealed that age, BMI, waist circumference, ALT, triglycerides, fasting glucose, uric acid and platelet count were associated with MAFLD.
MAFLD is prevalent in China and varies considerably among different age, sex, BMI, and female menopausal status groups. MAFLD is related to metabolic disorders, especially obesity, while metabolic disorders also play important roles in the occurrence of MAFLD in nonobese individuals. MAFLD patients exhibit a high prevalence of MS, dyslipidaemia, hyperuricaemia, and elevated liver enzymes. MAFLD tends to coexist with systemic metabolic disorders, and a deep inner relationship may exist between MAFLD and MS. Metabolic disorders should be considered to improve the management of MAFLD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The one-step quantum secure direct communication (QSDC) (
Sci. Bull.
67
, 367 (2022)) can effectively simplify QSDC’s operation and reduce message loss. For enhancing its security under practical ...experimental condition, we propose two measurement-device-independent (MDI) one-step QSDC protocols, which can resist all possible attacks from imperfect measurement devices. In both protocols, the communication parties prepare identical polarization-spatial-mode two-photon hyperentangled states and construct the hyperentanglement channel by hyperentanglement swapping. The first MDI one-step QSDC protocol adopts the nonlinear-optical complete hyperentanglement Bell state measurement (HBSM) to construct the hyperentanglement channel, while the second protocol adopts the linear-optical partial HBSM. Then, the parties encode the photons in the polarization degree of freedom and send them to the third party for the hyperentanglement-assisted complete polarization Bell state measurement. Both protocols are unconditionally secure in theory. The simulation results show the MDI one-step QSDC protocol with complete HBSM attains the maximal communication distance of about 354 km. Our MDI one-step QSDC protocols may have potential applications in the future quantum secure communication field.
A facile and efficient visible-light-mediated method for directly converting 1,4-naphthoquinones into dihydrocyclo-butabnaphthalene-3,8-diones (DHCBNDOs) under mild and clean conditions without using ...any photocatalysts is reported. This approach exhibited favorable compatibility with functional groups and afforded a series of DHCBNDOs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.
Invited for the cover of this issue is Guigen Li and co‐workers at Texas Tech University and Nanjing University. The cover artwork shows that chirality phenomena exists in the universe and in nature, ...including at micro and molecular levels. Read the full text of the article at 10.1002/chem.202100700.
“Here, we discuss a new form of chirality, multilayer 3D chirality. This work presents the first asymmetric catalytic approach to multi‐layer 3D chirality and shows that one of the aromatic rings of phosphorous oxide can be a parallel plane of this chirality.” Read more about the story behind the cover in the Cover Profile and about the research itself on page 8013 ff. (DOI: 10.1002/chem.202100700).
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