NSUN2 mediates distinct pathways to regulate enterovirus 71 replication.

Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine (m5C) modifications on viral RNAs, which are essential for the replication of various viruses. Despite the function of m5C deposition is well characterized, other potential roles of NSUN2 in regulating viral replication remain largely unknown. In this study, the m5C modified residues catalyzed by NSUN2 on enterovirus 71 (EV71) RNAs were mapped. NSUN2, along with m5C modifications, played multiple roles during the EV71 life cycle. Functional m5C modified nucleotides increased the translational efficiency and stability of EV71 RNAs. Additionally, NSUN2 was found to target the viral protein VP1 for binding and promote its stability by inhibiting the ubiquitination. Furthermore, both viral replication and pathogenicity in mice were largely attenuated when functional m5C residues were mutated. Taken together, this study characterizes distinct pathways mediated by NSUN2 in regulating EV71 replication, and highlights the importance of its catalyzed m5C modifications on EV71 RNAs for the viral replication and pathogenicity.

Synthesis of Polylactic Acid Oligomers for Broad-Spectrum Antimicrobials.

Infectious microbial diseases are a major public health hazard, calling for more innovative antimicrobials. Herein, polylactic acid (PLA) oligomers have been explored and reported as a bio-safe and eco-friendly functional antimicrobial agent against pathogens, such as viruses (H1N1, H3N2, and SARS-CoV-2), bacteria (E. coli, S. aureus, K. pneumoniae, MRSA), and fungi (C. albicans). The PLA oligomers were prepared by direct catalyst-free condensation polymerization of l-lactic acid monomers and characterized by FT-IR and 1H-NMR. The antiviral results demonstrate that PLA oligomers possess robust (inhibiting rate > 99%) and rapid (<20 min) antiviral activity against two pandemic ssRNA viruses, including influenza A virus (IAV) and coronavirus (CoV). Furthermore, the PLA oligomers exhibit high antibacterial activities against both Gram negative (G−) and Gram positive (G+) bacteria. The PLA oligomers also perform efficiently in killing a large amount of C. albicans as high as 105 cfu/mL down to zero at the concentration of 10 mg/mL. Thus, the broad-spectrum antimicrobial activity endowed the PLA oligomers with a promising biocidal option, except antibiotics in a wide range of applications, such as medical textiles, food preservation, water disinfection, and personal hygiene, in light of their unique biodegradability and biocompatibility.

N4-acetylcytidine regulates the replication and pathogenicity of enterovirus 71.

Chemical modifications are important for RNA function and metabolism. N4-acetylcytidine (ac4C) is critical for the translation and stability of mRNA. Although ac4C is found in RNA viruses, the detailed mechanisms through which ac4C affects viral replication are unclear. Here, we reported that the 5' untranslated region of the enterovirus 71 (EV71) genome was ac4C modified by the host acetyltransferase NAT10. Inhibition of NAT10 and mutation of the ac4C sites within the internal ribosomal entry site (IRES) suppressed EV71 replication. ac4C enhanced viral RNA translation via selective recruitment of PCBP2 to the IRES and boosted RNA stability. Additionally, ac4C increased the binding of RNA-dependent RNA polymerase (3D) to viral RNA. Notably, ac4C-deficient mutant EV71 showed reduced pathogenicity in vivo. Our findings highlighted the essential role of ac4C in EV71 infection and provided insights into potential antiviral treatments.

A Novel Hybrid Algorithm for the Forward Kinematics Problem of 6 DOF Based on Neural Networks.

The closed kinematic structure of Gough-Stewart platforms causes the kinematic control problem, particularly forward kinematics. In the traditional hybrid algorithm (backpropagation neural network and Newton-Raphson), it is difficult for the neural network part to train different datasets, causing training errors. Moreover, the Newton-Raphson method is unable to operate on a singular Jacobian matrix. In this study, in order to solve the forward kinematics problem of Gough-Stewart platforms, a new hybrid algorithm is proposed based on the combination of an artificial bee colony (ABC)-optimized BP neural network (ABC-BPNN) and a numerical algorithm. ABC greatly improves the prediction ability of neural networks and can provide a superb initial value to numerical algorithms. In the design of numerical algorithms, a modification of Newton's method (QMn-M) is introduced to solve the problem that the traditional algorithm model cannot be solved when it is trapped in singular matrix. Results show that the maximal improvement in ABC-BPNN error optimization was 46.3%, while the RMSE index decreased by 42.1%. Experiments showed the feasibility of QMn-M in solving singular matrix data, while the percentage improvement in performance for the average number of iterations and required time was 14.4% and 13.9%, respectively.

Constant Tension Control System of High-Voltage Coil Winding Machine Based on Smith Predictor-Optimized Active Disturbance Rejection Control Algorithm.

In the production process of high-voltage coils, a constant tension control system is designed to improve the quality of the transformer. The system is composed of a controller, execution structure, detection structure, etc. The active disturbance rejection control (ADRC), optimized by the Smith predictor (SP), is adopted to achieve constant tension control. The experiment results show that the tension control system based on the SP-ADRC has higher control accuracy, shorter stabilization time and stronger anti-interference ability compared with the traditional PID algorithm. The actual experiment shows that the constant tension control system of the high-voltage coil winding machine based on SP-ADRC has a superior control effect and high practical value.

Attitudes Toward Advance Directives Among Patients and Their Family Members in China.

OBJECTIVES: Chinese people are generally unfamiliar with the concept of advance care planning or advance directives (ACP/ADs), which raises dilemmas in life-support choice and can even affect clinical decision making. To understand and address the issues involved better, we investigated the awareness of ACP/ADs in China, as well as people's attitudes toward medical autonomy and end-of-life care. DESIGN: A multicenter cross-sectional survey, conducted from August 1 to December 31, 2016. SETTING: Twenty-five hospitals located in 15 different provinces throughout mainland China. PARTICIPANTS: Pairs of adult patients without dementia or malignancies, and a family member. MEASUREMENTS: Participants self-filled anonymous questionnaires, and the data collected were analyzed to relate patients' sociodemographic characteristics to their awareness of ACP/ADs and attitudes to health care autonomy and end-of-life care. RESULTS: Among 1084 patients who completed the questionnaire, 415 (38.3%) had heard about ACP/ADs. Having been informed about ACP/ADs, 995 (91.8%) were willing to find out their true health status and decide for themselves; 549 (50.6%) wanted to institute ACP/ADs. Regarding end-of-life care, 473 (43.6%) chose Do Not Resuscitate, and 435 (40.1%) wished to forgo life-support treatment if irreversibly moribund. Patients predominantly (481, 44.4%) chose general hospital as their preferred place to spend their last days of life; only 114 (10.5%) favored a special hospice facility. Patients' main concerns during end-of-life care were symptom control (35.1%), followed by functional maintenance and quality of life (29.8%), and prolonging life (18.9%). More highly educated patients had significantly greater awareness of ACP/ADs than less well educated ones (χ2 = 59.22, P < .001) and were more willing to find out the truth for themselves (χ2 = 58.30, P ≤ .001) and make medical decisions in advance (χ2 = 55.92, P < .001). Younger patients were also more willing than older ones to know the truth (χ2 = 38.23, P = .001) and make medical decisions in advance (χ2 = 18.42, P = .018), and were also more likely to wish to die at home (χ2 = 96.25, P < .001). Only 212 patients' family members (19.6%) wanted life-support treatment for themselves if irreversibly moribund, whereas 592 (54.6%) would want their relative to receive such procedures in the same circumstances; a similar discrepancy was evident for end-of-life invasive treatment (18.3% vs 42.7%). CONCLUSIONS: Awareness about ACP/ADs in China is still low. Providing culturally sensitive knowledge, education, and communication regarding ACP/ADs is a feasible first step to promoting this sociomedical practice.

Impact of Alzheimer's Disease in Nine Asian Countries.

BACKGROUND: Asia will soon have the majority of demented patients in the world. OBJECTIVE: To assess dementia using a uniform data system to update the current status of dementia in Asia. METHODS: A uniformed data set was administered in Taiwan, China, Hong Kong, Korea, Japan, Philippines, Thailand, Singapore, and Indonesia to gather data with regard to Alzheimer's disease (AD) and its related issues for these countries. RESULTS: In total, 2,370 AD patients and their caregivers were recruited from 2011 to 2014. The demographic characteristics of these patients and the relationships between patients and caregivers were different among individuals in these countries (p < 0.001). Of note, the family history for having dementia was 8.2% for females in contrast to 3.2% for males. CONCLUSION: Our study highlighted the differences in dementia assessment and care in developing versus developed countries. Greater effort with regard to studying dementia, especially in developing countries, is necessary.

Optimal cutoff scores for dementia and mild cognitive impairment of the Montreal Cognitive Assessment among elderly and oldest-old Chinese population.

BACKGROUND: All versions of the Montreal Cognitive Assessment (MoCA) lack population-based data of 80-plus individuals. The norms and cut-off scores for mild cognitive impairment (MCI) and dementia of the MoCA are different among five Chinese versions. OBJECTIVE: To provide the cut-off scores in detecting MCI and dementia of the Peking Medical Union College Hospital version of the MoCA (MoCA-P). METHODS: In a cross-sectional survey, Chinese veterans aged ≥60 years completed the MoCA-P and the Mini-Mental State Examination (MMSE). RESULTS: Among 7,445 elderly veterans, 5,085 (68.30%) were aged ≥80 years old, 2,621 (35.20%) had 6 years of education or less, 6,847 (91.97%) were male, and 2,311 (31.04%) and 984 (13.22%) veterans were diagnosed as having MCI and dementia, respectively. Adding two points and one point to the MoCA scores for the primary and middle school groups, respectively, can fully adjust for the notable impact of education but cannot compensate for the effect of age. In the three age groups (60-79, 80-89, and ≥90 years old), the optimal MoCA-P cut-off scores for detecting MCI were ≤25, ≤24, and ≤23, respectively, and for detecting dementia were ≤24, ≤21, and ≤19, respectively, which demonstrated relatively high sensitivities and specificities. The areas under the curves for the MoCA-P for detecting MCI and dementia (0.937 and 0.908, respectively) were greater than those for the MMSE (0.848 and 0.892, respectively). CONCLUSION: Compared with the MMSE, the MoCA-P is significantly better for detecting MCI in the elderly, particularly in the oldest old population, and it also displays more effectiveness in detecting dementia.

Construction of the Chinese Veteran Clinical Research (CVCR) platform for the assessment of non-communicable diseases.

BACKGROUND: Based on the excellent medical care and management system for Chinese veterans, as well as the detailed medical documentation available, we aim to construct a Chinese Veteran Clinical Research (CVCR) platform on non-communicable diseases (NCDs) and carry out studies of the primary disabling NCDs. METHODS: The Geriatric Neurology Department of Chinese People's Liberation Army General Hospital and veterans' hospitals serve as the leading and participating units in the platform construction. The fundamental constituents of the platform are veteran communities. Stratified typical cluster sampling is adopted to recruit veteran communities. A cross-sectional study of mental, neurological, and substance use (MNS) disorders are performed in two stages using screening scale such as the Mini-Mental State Examination and Montreal cognitive assessment, followed by systematic neuropsychological assessments to make clinical diagnoses, evaluated disease awareness and care situation. RESULTS: A total of 9 676 among 277 veteran communities from 18 cities are recruited into this platform, yielding a response rate of 83.86%. 8 812 subjects complete the MNS subproject screening and total response rate is 91.70%. The average participant age is (82.01±4.61) years, 69.47% of veterans are 80 years or older. Most participants are male (94.01%), 83.36% of subjects have at least a junior high school degree. The overall health status of veterans is good and stable. The most common NCD are cardiovascular disorders (86.44%), urinary and genital diseases (73.14%), eye and ear problems (66.25%), endocrine (56.56%) and neuro-psychiatric disturbances (50.78%). CONCLUSION: We first construct a veterans' comprehensive clinical research platform for the study of NCDs that is primarily composed of highly educated Chinese males of advanced age and utilize this platform to complete a cross-sectional national investigation of MNS disorders among veterans. The good and stable health condition of the veterans could facilitate the long-term follow-up studies of NCDs and provide prospective data to the prevention and management of NCDs.