Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16

The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5' end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2'-O-methyltransferase and NSP14 through its N7 methyltransferase activity, which are essential for the replication of the viral genome as well as evading the host's innate immunity. NSP10 acts as a crucial cofactor and stimulator of NSP14 and NSP16. To further understand the role of NSP10, we carried out a comprehensive analysis of >13 million globally collected whole-genome sequences (WGS) of SARS-CoV-2 obtained from the Global Initiative Sharing All Influenza Data (GISAID) and compared it with the reference genome Wuhan/WIV04/2019 to identify all currently known variants in NSP10. T12I, T102I, and A104V in NSP10 have been identified as the three most frequent variants and characterized using X-ray crystallography, biophysical assays, and enhanced sampling simulations. In contrast to other proteins such as spike and NSP6, NSP10 is significantly less prone to mutation due to its crucial role in replication. The functional effects of the variants were examined for their impact on the binding affinity and stability of both NSP14-NSP10 and NSP16-NSP10 complexes. These results highlight the limited changes induced by variant evolution in NSP10 and reflect on the critical roles NSP10 plays during the SARS-CoV-2 life cycle. These results also indicate that there is limited capacity for the virus to overcome inhibitors targeting NSP10 via the generation of variants in inhibitor binding pockets

Disseminated tuberculosis in a child during the COVID-19 pandemic: a case report and literature review

BackgroundDisseminated tuberculosis is an uncommon but devastating form of tuberculosis, possibly developing with the immune response of patients. COVID-19 infection may produce an immunosuppressive effect with possible implications for tuberculosis dissemination.Case presentationA 17-year-old female patient with a history of tuberculous pleurisy presented to the hospital with a high fever and life-threatening dyspnea after contracting a COVID-19 infection. Her condition deteriorated rapidly with grand mal epilepsy and acute gastrointestinal bleeding with a grossly depressed CD4 T-cell count, which was indicative of her profoundly immunosuppressed state. After identifying Mycobacterium tuberculosis in her cerebrospinal fluid and a subcutaneous abscess in her left lower back, she was diagnosed with disseminated tuberculosis involving both lungs, the central nervous system, the terminal ileum, the liver, bilateral adnexal tissue, and subcutaneous soft tissue in accordance with the chest and abdominal CT. Empirical treatment was initiated with dexamethasone (5 mg/day) and an anti-tuberculosis regimen of isoniazid, rifampicin, pyrazinamide, amikacin, and meropenem, which was replaced with faropenem after she left the hospital. The therapeutic effect was considered satisfied in the second month of follow-up.ConclusionTo the best of our knowledge, we report the first case report of disseminated tuberculosis after COVID-19 infection. Tuberculosis may disseminate and progress during the COVID-19 pandemic, requiring more significant studies to provide better diagnosis and treatment options for the co-infection

Comparative clinical-related outcomes of Chinese patent medicines for cardiac hypertrophy: A systematic review and network meta-analysis of randomized clinical trials

Background: Persistent pathological cardiac hypertrophy has been associated with increased risk of heart failure and even sudden death. Multiple Chinese patent medicines (CPMs) have gained attention as alternative and complementary remedies due to their high efficiency and few side effects. However, the effects of CPM-related treatment regimens for cardiac hypertrophy had not been systematically evaluated.Aim: The objective of this study was to estimate and compare the effectiveness of different mechanisms of CPMs to improve clinical outcomes, including clinical efficacy and echocardiographic indices, in the treatment of cardiac hypertrophy patents.Methods: A network meta-analysis was conducted on CPM-related randomized controlled trials (RCTs) published between 2012 and 2022 involving cardiac hypertrophy patients from four foreign and four Chinese databases. The outcomes concerned efficacy and related indicators, including echocardiographic indices, cardiac biomarkers, and functional exercise capacity, which were evaluated as odds ratios, mean differences, and 95% credible intervals. Network plots, league tables, surface-under-the-cumulative ranking (SUCRA), and funnel plots were created for each outcome, and all analyses were conducted using Stata 16.0 software.Results: A total of 25 RCTs were evaluated; these involved 2395 patients in a network meta-analysis (NMA). The results from existing evidence indicate that blood-activating and stasis-removing Chinese patent medicine (BASR-CPM) + Western medicine (WM) showed a good improvement in clinical efficacy (OR = 8.27; 95%CI = 0.97, 70.73). A combined treatment regimen of CPM with a function of qi-replenishing, blood-activating and stasis-removing, and Western medicine was an effective treatment regimen for echocardiographic indices such as decreasing left ventricular end-systolic dimension (LVESD) (SMD = −2.35; 95%CI = −3.09, −1.62) and left ventricular mass index (LVMI) (SMD = −1.73; 95%CI = −2.92, −0.54). Furthermore, KWYR-CPM + WM and BASR-CPM also showed good improvement for echocardiographic indices of LVEDD (SMD = −1.84; 95%CI = −3.46, −0.22) and left ventricular ejection fraction (SMD = 1.90; 95%CI = −0.46, −3.35), respectively.Conclusion: The study showed that BASR-CPM + WM may be the potentially superior treatment regimen for improving clinical efficacy among cardiac hypertrophy patients. QR&BASR-CPM + WM might be the optimal treatment for decreasing LVESD and LVMI. However, due to potential risks from bias and limited RCTs, further studies with larger samples and high-quality RCTs are needed to support these findings.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=329589],identifier [CRD42022329589]

In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine

Serum and plasma contain abundant biological information that reflect the body’s physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum. Methods: To address this challenge, we developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across ~10 orders or magnitude by combining data obtained from Data Independent Acquisition Mass Spectrometry (DIA-MS) and customizable antibody microarrays. Results: Using psoriasis as a proof-of-concept disease model, we screened 50 serum proteomes from healthy controls and psoriasis patients before and after treatment with traditional Chinese medicine (YinXieLing) on our in-depth serum proteomics platform. We identified 106 differentially-expressed proteins in psoriasis patients involved in psoriasis-relevant biological processes, such as blood coagulation, inflammation, apoptosis and angiogenesis signaling pathways. In addition, unbiased clustering and principle component analysis revealed 58 proteins discriminating healthy volunteers from psoriasis patients and 12 proteins distinguishing responders from non-responders to YinXieLing. To further demonstrate the clinical utility of our platform, we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index (PASI) score with three serum proteins (PI3, CCL22, IL-12B). Conclusion: Taken together, these results demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers of psoriasis and other immune-mediated diseases

Research on the Application of Digital Media Art in Film and Television Animation in Multimedia Perspective

The fusion of digital media art with film and television animation production ushers in a new artistic and technological synergy era. This form of art, merging visual, sound, and digital innovations, faces unparalleled growth opportunities and significant challenges. This paper investigates the impact of digital media art on animation, emphasizing its influence on creative expression and production processes. Through case study analysis, we demonstrate the efficiency gains and aesthetic enhancements afforded by digital media, including a 70% reduction in rendering time and a 40% increase in character animation realism. Incorporating Virtual Reality (V.R.) and Augmented Reality (A.R.) technologies also opens up novel avenues for immersive viewer experiences. Despite facing obstacles in technology adaptation and financial investment, the application of digital media art in animation represents a crucial driver of industry evolution

Molar mass and temperature dependence of the thermodiffusion of polyethylene oxide in water/ethanol mixtures

In this work we study the molar mass dependence of the thermodiffusion of polyethylene oxide at different temperatures in ethanol, water/ethanol mixture (c_water=0.7) and water in a molar mass range up to M_w=180000 g/mol. Due to the low solubility of polyethylene oxide oligomers in ethanol the measurements are limited up to M_w=2200 g/mol. The specific water/ethanol concentration 0.7 has been chosen, because at this weight fraction the thermal diffusion coefficient, D_T, of water/ethanol vanishes so that the system can be treated as a pseudo binary mixture. The addition of ethanol will degrade the solvent quality, so that we expect a change of the interaction energies between polymer and solvent. The analysis of the experimental data within a theoretical model shows the need of a refined model, which takes specific interactions into account

Influences of Shading on Ascorbic Acid Biosynthesis of Blackcurrant (Ribes nigrum L.)

Cultivation conditions may greatly affect fruit quality, especially in the accumulation of functional metabolites. Blackcurrant fruits (Ribes nigrum L.) have high ascorbic acid (AsA) concentrations. The purpose of the current study was to investigate the influence of different shading treatments (full sunlight, and 40% and 60% sunlight) on the fruits’ maturity, and on the levels of fruit firmness, soluble solid, AsA, and enzyme activity involved in AsA biosynthesis and recycling in two blackcurrant (Ribes nigrum) cultivars, ‘Heifeng’ and ‘Adelinia’. Shading conditions of 40% and 60% sunlight delayed fruit ripening and increased fruit firmness in both ‘Adelinia’ and ‘Heifeng’. Soluble solids in ‘Adelinia’ were markedly reduced by shading compared with ‘Heifeng’. Compared with full sunlight, the AsA content was significantly decreased in the ripe fruits under the 40% and 60% shading treatments. Additionally, the AsA content was decreased during the fruit development process under the 60% shading treatment, which was associated with the reduced activity of the enzymes monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), glutathione oxidoreductase (GR), ascorbate peroxidase (APX), and L-galactose dehydrogenase (GalDH) involved in the biosynthesis and recycling pathway of AsA. The correlation analysis results showed that the activity of MDHAR, DHAR, GR, APX, and GalDH was significantly positively correlated with AsA concentrations during the 60% shading treatment in ‘Adelinia’ and ‘Heifeng’ fruits, suggesting that AsA biosynthesis and recycling were affected and the two cultivars have similar mechanisms to deal with shading. Our results not only provide a better understanding of the regulation mechanism of AsA accumulation under shading, but also provide a theoretical basis for taking effective cultivation measures aimed at the improvement of AsA levels in blackcurrant fruits

Influences of Shading on Ascorbic Acid Biosynthesis of Blackcurrant (<i>Ribes nigrum</i> L.)

Cultivation conditions may greatly affect fruit quality, especially in the accumulation of functional metabolites. Blackcurrant fruits (Ribes nigrum L.) have high ascorbic acid (AsA) concentrations. The purpose of the current study was to investigate the influence of different shading treatments (full sunlight, and 40% and 60% sunlight) on the fruits’ maturity, and on the levels of fruit firmness, soluble solid, AsA, and enzyme activity involved in AsA biosynthesis and recycling in two blackcurrant (Ribes nigrum) cultivars, ‘Heifeng’ and ‘Adelinia’. Shading conditions of 40% and 60% sunlight delayed fruit ripening and increased fruit firmness in both ‘Adelinia’ and ‘Heifeng’. Soluble solids in ‘Adelinia’ were markedly reduced by shading compared with ‘Heifeng’. Compared with full sunlight, the AsA content was significantly decreased in the ripe fruits under the 40% and 60% shading treatments. Additionally, the AsA content was decreased during the fruit development process under the 60% shading treatment, which was associated with the reduced activity of the enzymes monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), glutathione oxidoreductase (GR), ascorbate peroxidase (APX), and L-galactose dehydrogenase (GalDH) involved in the biosynthesis and recycling pathway of AsA. The correlation analysis results showed that the activity of MDHAR, DHAR, GR, APX, and GalDH was significantly positively correlated with AsA concentrations during the 60% shading treatment in ‘Adelinia’ and ‘Heifeng’ fruits, suggesting that AsA biosynthesis and recycling were affected and the two cultivars have similar mechanisms to deal with shading. Our results not only provide a better understanding of the regulation mechanism of AsA accumulation under shading, but also provide a theoretical basis for taking effective cultivation measures aimed at the improvement of AsA levels in blackcurrant fruits

Clinical study of the effect of refractive status on stereopsis in children with intermittent exotropia

Abstract Background Many studies have shown that patients with intermittent exotropia have different degrees of damage to their stereopsis function. The purpose of this study is to explore the effect of different refractive status on stereopsis in children with intermittent exotropia(IXT). Methods We assessed 90 children of ages 4~ 16 years with intermittent exotropia at the Second Affiliated Hospital of Dalian Medical University during the years 2016–2017. According to their refractive status, the patients were divided into hyperopia group(spherical equivalent > or = − 1.00 diopters), myopia group(spherical equivalent  or = 1.50 diopter). The distant stereopsis of the patient was checked by the synoptophore, and the near stereopsis of the patients was checked by the Titmus stereogram. Then, we compared the difference between distant stereopsis and near stereopsis in the four groups. Results (1)The retention rates of distant stereopsis in the hyperopia group, emmetropia group, myopia group and anisometropia group were 33.3, 45.2, 34.6, and 33.3%, respectively. There was no significant difference between the groups with different refractive status. (2)The retention rates of near stereopsis in the hyperopia group, emmetropia group, myopia group and anisometropia group were 66.7, 83.9, 80.8, and 55.6%, respectively. There were statistically significant differences between the emmetropia group and the anisometropia group (P = 0.030). (3)The retention rate of distant stereopsis in children with intermittent exotropia was 37.8%, and the retention rate of near stereopsis was 74.4%. The difference between the two groups was statistically significant (P = 0.019). Conclusions The damage to distant stereopsis in children with intermittent exotropia is more serious than that to near stereopsis. The damage to near stereopsis in children with intermittent exotropia and anisometropiais more serious