[Advances of proteostasis network and its stability maintenance mechanism].

Protein is fundamental to life, as it generates protein variants. The maintenance of a dynamic equilibrium in these protein variants, known as protein homeostasis, is crucial for cellular function. Various factors, both endogenous and exogenous, can disrupt protein homeostasis during protein synthesis. These factors include translational error, and biological functions mediated by regulatory factors, and more. When cell accumulate proteins with folding errors, it impairs protein homeostasis, leading to the development of related diseases. In response to protein folding errors, multiple monitoring mechanisms are activated to mediate pathways that sustain the dynamic equilibrium. This review highlights the complex relationships within the proteostasis network, which are influenced by a variety of factors. These insights potentially provide new directions for studying diseases caused by protein synthesis errors.

Analysis for codon usage bias in membrane anchor of nonstructural protein 5A from BVDV.

The nonstructural protein 5A (NS5A) of the bovine viral diarrhea virus (BVDV) is a monotopic membrane protein. This protein can anchor to the cell membrane by an in-plane amphipathic ⍺-helix, which participates in the viral replication complex. In this study, the effects of synonymous codon usage pattern of NS5A and the overall transfer RNA (tRNA) abundance in cells on the formation of the in-plane membrane anchor of NS5A were analyzed, based on NS5A coding sequences of different BVDV genotypes. BVDV NS5A coding sequences represent the most potential for BVDV genotyping. Moreover, the nucleotide usage of BVDV NS5A dominates the genotype-specific pattern of synonymous codon usage. There is an obvious relationship between synonymous codon usage bias and the spatial conformation of the in-plane membrane anchor. Furthermore, the overall tRNA abundance profiling displays that codon positions with a high level of tRNA abundance are more than ones with a low level of tRNA abundance in the in-plane membrane anchor, implying that high translation speed probably acts on the spatial conformation of in-plane membrane anchor of BVDV NS5A. These results give a new opinion on the effect of codon usage bias in the formation of the in-plane membrane anchor of BVDV NS5A.

Nucleotide and codon usage biases involved in the evolution of African swine fever virus: A comparative genomics analysis.

Since African swine fever virus (ASFV) replication is closely related to its host's machinery, codon usage of viral genome can be subject to selection pressures. A better understanding of codon usage can give new insights into viral evolution. We implemented information entropy and revealed that the nucleotide usage pattern of ASFV is significantly associated with viral isolation factors (region and time), especially the usages of thymine and cytosine. Despite the domination of adenine and thymine in the viral genome, we found that mutation pressure alters the overall codon usage pattern of ASFV, followed by selective forces from natural selection. Moreover, the nucleotide skew index at the gene level indicates that nucleotide usages influencing synonymous codon bias of ASFV are significantly correlated with viral protein hydropathy. Finally, evolutionary plasticity is proved to contribute to the weakness in synonymous codons with A- or T-end serving as optimal codons of ASFV, suggesting that fine-tuning translation selection plays a role in synonymous codon usages of ASFV for adapting host. Taken together, ASFV is subject to evolutionary dynamics on nucleotide selections and synonymous codon usage, and our detailed analysis offers deeper insights into the genetic characteristics of this newly emerging virus around the world.

Study on the interaction of taiwaniaquinoids with FTO by spectroscopy and molecular modeling.

In this work, an attempt has been made to study the interaction of four taiwaniaquinoids with fat mass and obesity-associated protein (FTO) by UV-vis absorption, fluorescence spectroscopy, and molecular docking techniques. The results indicated that taiwaniaquinoids effectively quenched the intrinsic fluorescence of FTO via static quenching. According to the binding constants and thermodynamic parameters at three different temperatures, the hydrophobic force and electrostatic interactions appeared be the predominant intermolecular forces in stabilizing the complex. Results revealed that W-4 was the strongest quencher and W-3 was the weakest. The results of synchronous and three-dimensional fluorescence spectra showed that the conformation of FTO was changed. In addition, the influence of molecular structure on the quenching effect has been investigated.

Concise Synthesis of Taiwaniaquinol B and 5-epi-Taiwaniaquinone G.

The natural product taiwaniaquinol B and the unnatural 5-epi-taiwaniaquinone G were synthesized based on a highly efficient tandem acylation-Nazarov cyclization approach to build the tricyclic skeleton.

Synthesis of 5-epi-taiwaniaquinone G.

A concise synthetic approach to the unnatural 5-epi-taiwaniaquinone G has been developed via a Lewis acid catalyzed tandem acylation-Nazarov cyclization reaction to construct the tricyclic skeleton, followed by installation of the isopropyl group through a strategy involving coumarin formation and its subsequent hydrolysis.

Epidemiological analysis of trauma patients following the Lushan earthquake.

BACKGROUND: A 7.0-magnitude earthquake hit Lushan County in China's Sichuan province on April 20, 2013, resulting in 196 deaths and 11,470 injured. This study was designed to analyze the characteristics of the injuries and the treatment of the seismic victims. METHODS: After the earthquake, an epidemiological survey of injured patients was conducted by the Health Department of Sichuan Province. Epidemiological survey tools included paper-and-pencil questionnaires and a data management system based on the Access Database. Questionnaires were completed based on the medical records of inpatients with earthquake-related injuries. Outpatients or non-seismic injured inpatients were excluded. A total of 2010 patients from 140 hospitals were included. RESULTS: The most common type of injuries involved bone fractures (58.3%). Children younger than 10 years of age suffered fewer fractures and chest injuries, but more skin and soft -tissue injuries. Patients older than 80 years were more likely to suffer hip and thigh fractures, pelvis fractures, and chest injuries, whereas adult patients suffered more ankle and foot fractures. A total of 207 cases of calcaneal fracture were due to high falling injuries related to extreme panic. The most common type of infection in hospitalized patients was pulmonary infections. A total of 70.5% patients had limb dysfunction, and 60.1% of this group received rehabilitation. Most patients received rehabilitation within 1 week, and the median duration of rehabilitation was 3 weeks. The cause of death of all seven hospitalized patients who died was severe traumatic brain injuries; five of this group died within 24 h after the earthquake. CONCLUSIONS: Injuries varied as a function of the age of the victim. As more injuries were indirectly caused by the Lushan earthquake, disaster education is urgently needed to avoid secondary injuries.

High prevalence of subclinical thyroid dysfunction and the relationship between thyrotropin levels and cardiovascular risk factors in residents of the coastal area of China.

OBJECTIVES: To investigate the prevalence of subclinical thyroid dysfunction and the relationship between thyrotropin levels and cardiovascular risk factors in residents of the coastal area of China. METHODS: Atotalof4256individuals(mean[±SD]age50.51±14.24years; 2079 males, 2177 females,) were enrolled in the present study. Sex, blood pressure, body mass index, waist-to-hip ratio, serum levels of fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid and smoking status were measured. The relationship between thyrotropin levels and cardiovascular risk factors was analyzed. RESULTS: The overall prevalence of thyroid dysfunction was 11.07%. The prevalence of subclinical hypothyroidism (6.32%) was higher than that of hyperthyroidism (1.53%). The prevalence of thyroid dysfunction among female subjects was higher than that among male subjects (16.54% versus 5.34%, respectively; P<0.001). Significant differences were detected with respect to body mass index (P=0.026), waist-to-hip ratio (P<0.001), fasting glucose levels (P=0.001), total cholesterol levels (P=0.013), triglyceride levels (P=0.003) and smoking status according to different thyrotropin levels. CONCLUSION: The prevalence of thyroid dysfunction was high in residents of China's coastal area. Significant differences were detected with regard to body mass index, waist-to-hip ratio, fasting glucose levels, total cholesterol levels, triglyceride levels and smoking status according to different thyrotropin levels.

A protein phosphatase 2A catalytic subunit modulates blue light-induced chloroplast avoidance movements through regulating actin cytoskeleton in Arabidopsis.

Chloroplast avoidance movements mediated by phototropin 2 (phot2) are one of most important physiological events in the response to high-fluence blue light (BL), which reduces damage to the photosynthetic machinery under excess light. Protein phosphatase 2A-2 (PP2A-2) is an isoform of the catalytic subunit of PP2A, which regulates a number of developmental processes. To investigate whether PP2A-2 was involved in high-fluence BL-induced chloroplast avoidance movements, we first analyzed chloroplast migration in the leaves of the pp2a-2 mutant in response to BL. The data showed that PP2A-2 might act as a positive regulator in phot2-mediated chloroplast avoidance movements, but not in phot1-mediated chloroplast accumulation movements. Then, the effect of okadaic acid (OA) and cantharidin (selective PP2A inhibitors) on high-fluence BL response was further investigated in Arabidopsis thaliana mesophyll cells. Within a certain concentration range, exogenously applied OA or cantharidin inhibited the high-fluence BL-induced chloroplast movements in a concentration-dependent manner. Actin depolymerizing factor (ADF)/cofilin phosphorylation assays demonstrated that PP2A-2 can activate/dephosphorylate ADF/cofilin, an actin-binding protein, in Arabidopsis mesophyll cells. Consistent with this observation, the experiments showed that OA could inhibit ADF1 binding to the actin and suppress the reorganization of the actin cytoskeleton after high-fluence BL irradiation. The adf1 and adf3 mutants also exhibited reduced high-fluence BL-induced chloroplast avoidance movements. In conclusion, we identified that PP2A-2 regulated the activation of ADF/cofilin, which, in turn, regulated actin cytoskeleton remodeling and was involved in phot2-mediated chloroplast avoidance movements.