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As an alternative mechanism for cap-dependent (m7GpppN) translation, internal ribosome entry site (IRES)-dependent translation has been observed in the 5' untranslated regions (5' UTR) and coding regions of a number of viral and eukaryotic mRNAs. In this study, a series of 5' terminal truncated structural protein genes that were fused with GFP was used to screen for potential IRESs, and IRESs were identified using a bicistronic luciferase vector or GFP expression vector possessing a hairpin structure. Our results revealed that a putative IRES was located between nt 1982 and 2281 in the VP3 coding region of the human rhinovirus 16 (HRV16) genomes. We also demonstrated that effective IRES-initiated protein expression in vitro did not occur through splicing sites or cryptic promoters. We confirmed that thapsigargin (TG), an inducer of endoplasmic reticulum stress (ERS), facilitated increased IRES activity in a dose-dependent manner. Additionally, the secondary structure of the IRES was predicted online using the RNAfold web server.

Since electric vehicle with in‐wheel motor has advantages in aspects of vehicle dynamics control and energy‐efficient control, it has been widely applied in the vehicle platoon in the highway. This paper proposes an optimization and control structure that integrates ecological cooperative adaptive cruise control (CACC) for the vehicle platoon, and path tracking and ecological control allocation (Eco‐CA) for individual vehicle to improve the energy efficiency of electric vehicles in traffic flow. First, in the upper layer, the suitable driving mode is selected by finite‐state machine (FSM) based on surrounding environment. Then the path‐planner and ecological CACC in the higher layer are proposed to determine the desired path and desired speed and acceleration profile. After that, in the middle layer, longitudinal motion controller and yaw stability controller are integrated to achieve the desired control targets from upper layer. Finally, in the lower layer, each in‐wheel motor torque is optimized by Eco‐CA subsystem to reduce the energy consumption of driving motor and tyre friction loss. The simulation results demonstrate that the proposed control strategy can improve the energy efficiency and dynamics control performance.

Background Treatment is indicated in dogs with preclinical degenerative mitral valve disease (DMVD) and cardiomegaly (stage B2). This is best diagnosed using echocardiography; however, relying upon this limits access to accurate diagnosis. Objectives To evaluate whether cardiac biomarker concentrations can be used alongside other clinical data to identify stage B2 dogs. Animals Client‐owned dogs (n = 1887) with preclinical DMVD prospectively sampled in Germany, the United Kingdom, and the United States. Methods Dogs that met inclusion criteria and were not receiving pimobendan (n = 1245) were used for model development. Explanatory (multivariable logistic regression) and predictive models were developed using clinical observations, biochemistry, and cardiac biomarker concentrations, with echocardiographically confirmed stage B2 disease as the outcome. Receiver operating characteristic curves assessed the ability to identify stage B2 dogs. Results Age, appetite, serum alanine aminotransferase activity, body condition, serum creatinine concentration, murmur intensity, and plasma N‐terminal propeptide of B‐type natriuretic peptide (NT‐proBNP) concentration were independently associated with the likelihood of being stage B2. The discriminatory ability of this explanatory model (area under curve [AUC], 0.84; 95% confidence interval [CI], 0.82‐0.87) was superior to NT‐proBNP (AUC, 0.77; 95% CI, 0.74‐0.80) or the vertebral heart score alone (AUC, 0.76; 95% CI, 0.69‐0.83). A predictive logistic regression model could identify the probability of being stage B2 (AUC test set, 0.86; 95% CI, 0.81‐0.91). Conclusion and Clinical Importance Our findings indicate accessible measurements could be used to screen dogs with preclinical DMVD. Encouraging at‐risk dogs to seek further evaluation could result in a greater proportion of cases being appropriately managed.

Backgrounds Kidney renal clear cell carcinoma (KIRC) is a major pathological type of renal cell carcinoma (RCC), and the prognosis of advanced KIRC patients is often unsatisfactory. Some lysine oxidase (LOX) family genes have been proven to be upregulated in some malignancies and play pivotal roles in the carcinogenesis. However, their roles in KIRC remain unclear. Materials and Methods Here, we used some online databases (eg, ONCOMINE, GEPIA, UALCAN, c‐BioPortal, Human Protein Altas) to comprehensively explored the expression levels and the prognostic values of LOX family genes in KIRC using bioinformatic methods. Results The results revealed that lysyl oxidase (LOX) and lysyl oxidase‐like 2 (LOXL2) were significantly overexpressed in KIRC at the level of mRNA expression, protein expression, and RCC cell lines. Further analysis demonstrated that higher mRNA expression of LOX and LOXL2 were significantly correlated with poor survival, tumor grade, individual cancer stages, and nodal metastasis status. DNA copy number amplifications and mRNA upregulation, DNA deep deletion, and mRNA upregulation were the main genetic mutations of LOX and LOXL2, respectively. Prognostic analysis showed that the altered group had significantly poorer overall survival (OS) compared to the unaltered group (p = .0387). Co‐expression analysis showed CP, PLOD2, and COL5A1 were significantly correlated with LOX, and COL1A2 was positively correlated with LOXL2. Further analysis confirmed that these co‐expressed genes were significantly upregulated and predicted unfavorable prognosis in KIRC. Conclusion Multi‐level analysis demonstrated that LOX and LOXL2 were significantly upregulated and predicted poor survival in KIRC, which may apply as promising biomarkers for diagnosis and therapy of KIRC in the future., We firstly comprehensively explored the role of LOX family genes in kidney renal clear cell carcinoma, and found that LOX and LOXL2 may be used as new therapeutic targets for kidney renal clear cell carcinoma.

We describe a photoinduced copper-catalyzed asymmetric radical decarboxylative alkynylation of bench-stable N-hydroxyphthalimide(NHP)-type esters of racemic alkyl carboxylic acids with terminal alkynes, which provides a flexible platform for the construction of chiral C(sp3 )-C(sp) bonds. Critical to the success of this process are not only the use of the copper catalyst as a dual photo- and cross-coupling catalyst but also tuning of the NHP-type esters to inhibit the facile homodimerization of the alkyl radical and terminal alkyne, respectively. Owing to the use of stable and easily available NHP-type esters, the reaction features a broader substrate scope compared with reactions using the alkyl halide counterparts, covering (hetero)benzyl-, allyl-, and aminocarbonyl-substituted carboxylic acid derivatives, and (hetero)aryl and alkyl as well as silyl alkynes, thus providing a vital complementary approach to the previously reported method.

Molecular self-assembly is widely used in the fields of biosensors, molecular devices, efficient catalytic materials, and medical biomaterials. As the carrier of genetic information, DNA is a kind of biomacromolecule composed of deoxyribonucleotide units. DNA nanotechnology extends DNA of its original properties as a molecule that stores and transmits genetic information from its biological environment by taking advantage of its unique base pairing and inherent biocompatibility to produce structurally-defined supramolecular structures. With the continuously development of DNA technology, the assembly method of DNA nanostructures is not only limited on the basis of DNA hybridization but also other biochemical interactions. In this review, we summarize the latest methods used to construct higher-order DNA structures. The problems of DNA nanostructures are discussed and the future directions in this field are provided.

Exercise training exerts protective effects against diabetic nephropathy. This study aimed to investigate whether exercise training could attenuate diabetic renal injury via regulating endogenous hydrogen sulfide (H2 S) production. First, C57BL/6 mice were allocated into the control, diabetes, exercise, and diabetes + exercise groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ). Treadmill exercise continued for four weeks. Second, mice was allocated into the control, diabetes, H2 S and diabetes + H2 S groups. H2 S donor sodium hydrosulfide (NaHS) was intraperitoneally injected once daily for four weeks. STZ-induced diabetic mice exhibited glomerular hypertrophy, tissue fibrosis and increased urine albumin levels, urine protein- and albumin-to-creatinine ratios, which were relieved by exercise training. Diabetic renal injury was associated with apoptotic cell death, as evidenced by the enhanced caspase-3 activity, the increased TdT-mediated dUTP nick-end labeling -positive cells and the reduced expression of anti-apoptotic proteins, all of which were attenuated by exercise training. Exercise training enhanced renal sirtuin 1 (SIRT1) expression in diabetic mice, accompanied by an inhibition of the p53-#ediated pro-apoptotic pathway. Furthermore, exercise training restored the STZ-mediated downregulation of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) and the reduced renal H2 S production. NaHS treatment restored SIRT1 expression, inhibited the p53-mediated pro-apoptotic pathway and attenuated diabetes-associated apoptosis and renal injury. In high glucose-treated MPC5 podocytes, NaHS treatment inhibited the p53-mediated pro-apoptotic pathway and podocyte apoptosis in a SIRT1-dependent manner. Collectively, exercise training upregulated CBS/CSE expression and enhanced the endogenous H2 S production in renal tissues, thereby contributing to the modulation of the SIRT1/p53 apoptosis pathway and improvement of diabetic nephropathy.

Hypoxic pulmonary arterial hypertension is characterized by elevated pulmonary vascular resistance and remodelling. Transforming growth factor-β1 (TGF-β1 ) is the master regulator in cellular response to hypoxia which can directly target lysyl oxidase (LOX). This study aimed to determine whether hypercapnia attenuates hypoxic pulmonary hypertension via regulating TGF-β1 and LOX signalling. We found that exposure to hypercapnia ameliorated the increase in mean pulmonary artery pressure (mPAP) and ratio of right ventricle to left ventricle plus septum (RV/(LV + S)) induced by hypoxia but had no effect on mPAP and RV/(LV + S) in normoxia-exposed control. In addition, exposure to hypoxia upregulated the mRNA and protein levels of LOX and TGF-β1 in rat PASMCs both in vivo and in vitro, but these effects were abrogated by concurrent exposure to hypercapnia. The downregulation of LOX in rat PASMCs induced by hypercapnia was reversed by the administration with TGF-β1 , while TGF-β1 knockdown repressed the upregulation of LOX in hypoxia-exposed rat PASMCs. In conclusion, hypoxia upregulates LOX and TGF-β1 expression in PASMCs and contributes to pulmonary hypertension. Hypercapnia downregulates hypoxia-induced LOX expression and alleviates hypoxia-associated pulmonary hypertension via inhibiting TGF-β1 signalling. SIGNIFICANCE OF THE STUDY: Hypoxia-induced upregulation of TGF-β1 , PDGF, and HIF-1α plays a pivotal role in PAH, but molecular mechanism of how hypoxia regulates LOX expression is not clear. In the present study, we showed that mRNA and protein expression levels of LOX were substantially increased when TGF-β1 was induced by hypoxia, and the effects were reversed by TGF-β1 knockdown. Our study indicates that TGF-β1 is implicated in the regulation of LOX.

Objectives Coronavirus disease 2019 (COVID‐19) is rapidly spreading worldwide. Lianhua Qingwen capsule (LQC) has shown therapeutic effects in patients with COVID‐19. This study is aimed to discover its molecular mechanism and provide potential drug targets. Materials and Methods An LQC target and COVID‐19–related gene set was established using the Traditional Chinese Medicine Systems Pharmacology database and seven disease‐gene databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein‐protein interaction (PPI) network were performed to discover the potential mechanism. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. Results A gene set of 65 genes was generated. We then constructed a compound‐target network that contained 234 nodes of active compounds and 916 edges of compound‐target pairs. The GO and KEGG indicated that LQC can act by regulating immune response, apoptosis and virus infection. PPI network and subnetworks identified nine hub genes. The molecular docking was conducted on the most significant gene Akt1, which is involved in lung injury, lung fibrogenesis and virus infection. Six active compounds of LQC can enter the active pocket of Akt1, namely beta‐carotene, kaempferol, luteolin, naringenin, quercetin and wogonin, thereby exerting potential therapeutic effects in COVID‐19. Conclusions The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of LQC. Akt1 is a promising drug target to reduce tissue damage and help eliminate virus infection., A Lianhua Qingwen capsule (LQC) target and COVID‐19 related gene set is established to construct compound‐target pharmacology network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicate the regulating effect of LQC on apoptosis, antivirus, immune defense, and inflammatory response. Protein‐protein interaction network and critical subnetworks are constructed to identify hub gene target. The most significant gene, Akt 1, is selected to perform molecular docking with active compounds of LQC. Six compounds are finally recognized as potential anti‐COVID‐19 agents.

Inspired by green plants, artificial photosynthesis has become one of the most attractive approaches toward carbon dioxide (CO2 ) valorization. Semiconductor quantum dots (QDs) or dot-in-rod (DIR) nano-heterostructures have gained substantial research interest in multielectron photoredox reactions. However, fast electron-hole recombination or sluggish hole transfer and utilization remains unsatisfactory for their potential applications. Here, the first application of a well-designed ZnSe/CdS dot-on-rods (DORs) nano-heterostructure for efficient and selective CO2 photoreduction with H2 O as an electron donor is presented. In-depth spectroscopic studies reveal that surface-anchored ZnSe QDs not only assist ultrafast (≈2 ps) electron and hole separation, but also promote interfacial hole transfer participating in oxidative half-reactions. Surface photovoltage (SPV) spectroscopy provides a direct image of spatially separated electrons in CdS and holes in ZnSe. Therefore, ZnSe/CdS DORs photocatalyze CO2 to CO with a rate of ≈11.3 µmol g-1 h-1 and ≥85% selectivity, much higher than that of ZnSe/CdS DIRs or pristine CdS nanorods under identical conditions. Obviously, favored energy-level alignment and unique morphology balance the utilization of electrons and holes in this nano-heterostructure, thus enhancing the performance of artificial photosynthetic solar-to-chemical conversion.