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Novel research and development (R&D) institutions are an important organizational form of scientific and technological innovation in China. Novel R&D institutions in life sciences and medicine are oriented toward people’s life and health and play an important role in promoting the development of life sciences and medicine, forming multiple innovation subjects, and building an innovation ecology with active elements. However, their construction is still in an exploration stage, and it is urgent to optimize the construction strategy and form a stable and sustainable development capability. This study used the methods of policy research, on-site research, case study, and expert consultation to summarize the progress of policy promotion and exploration practices of novel R&D institutions in China, analyzed the construction modes and operation mechanisms of similar R&D institutions abroad, and presented challenges in the development of novel R&D institutions in the field of life sciences and medicine in China. On this basis, we proposed the following strategies for optimizing the construction of novel R&D institutions in life sciences and medicine in China: (1) building up a diversified and stable funding mechanism, (2) establishing a differentiated development path, (3) improving the recruiting and cultivating mechanism of outstanding professionals, (4) continuously innovating the organizational form of scientific research, (5) exploiting the advantages of the flexible mechanism for scientific achievement transformation, and (6) enhancing the academic influence of these institutions, thereby promoting the high-quality development of these institutions and the self-reliance and strength of China in science and technology.

Objective To explore the mechanisms of transcription factor circadian locomalor output cycles kaput(CLOCK) in mediating regulatory function of endogenous hydrogen peroxide(H2O2) for cell respiration. Methods Cellular oxygen consumption capacity and glycolysis in ClockC195S mouse embryonic fibroblasts (MEFs) and adult fibroblasts(MAFs) were tested by Agilent Seahorse XF Cell Mito Stress Test Kit and Glycolysis Stress Test Kit. The expression of key genes participating in cell respiration was detected by q-PCR. The endogenous H2O2 levels and the redox modification of CLOCK were detected by Amplex® Red Hydrogen Peroxide/Peroxidase Assay Kit and biotin-conjugated iodoacetamide (BIAM) were used respectively after the treatment of antioxidant Trolox. Changes in the oxygen consumption capacity and in key respiratory gene expression after the treatment of antioxidant Trolox were also tested in Clockwt and ClockC195S MEFs. Results Cellular oxygen consumption capacity, glycolysis and the expression of NMNAT2, a key enzyme in nicotinamide adenine denudeotide(NAD) biosynthesis, as well as NAD content all decreased in ClockC195S MEFs. The treatment with Trolox decreased endogenous H2O2 level and dampened respiration capacity in Clockwt MEFs but not in ClockC195S MEFs. Conclusions CLOCK mediates the regulation of endogenous H2O2 for cellular respiration through its redox modification at Cys195.

China’s science and technology support system has played a significant role in fighting public health emergencies. In this study, we summarize the construction status of China’s science and technology support system for emergencies from the aspects of (1) layout of scientific research bases and platforms, (2) application of big data technology, (3) science and technology investment in public health, and (4) transformation of scientific and technological achievements. Subsequently, we analyze the challenges for the construction of the support system in China in comparison with developed countries that are advanced regarding medical science and technology. To solve the problems of weak foundation of basic medical research and lack of key core technologies, we suggest to strengthen the synergy of universities, medical institutions, and science and technology enterprises. This will improve China’s basic medical research ability and promote the research and development of original pharmaceutical products and diagnostic reagents. In view of the lack of bases and platform facilities in China, we suggest to strengthen the construction of national biological resource sample centers and build self-supported data and information sharing platforms. As for insufficient investment in public health and an imperfect personnel system, we suggest to enhance the leading role of the National Academy of Medical Sciences, increase the input of public health, and improve the personnel evaluation, reserve, and training mechanisms.

Public health emergencies severely affect people’s lives and health, national security, social stability, and economic development. Against the background of coronavirus disease 2019 pandemic, this study analyzes the current status of China’s public health emergency prevention and control system from the aspects of its six major systems: monitoring, early warning, and evaluation; diagnosis and treatment; basic scientific research; personnel training; material, equipment, and industry support; and social mobilization and coordinated action. We conclude that strengthening system construction is a realistic demand of China in the new development stage. China’s public health system still faces challenges regarding institutional positioning, capacity building, hardware investment, and management system. Therefore, we propose that China should establish a national overall coordination and emergency command mechanism, strengthen clinical, science, education, and industrial support capacity, and further promote international cooperation.

This study systematically investigates the enhancement effects of different fiber-reinforced polymer (FRP) materials on the axial compressive performance of concrete. Through experimental evaluations of single-layer, double-layer, and composite FRP reinforcement techniques, the impact of various FRP materials and their combinations on concrete's axial compressive strength and deformation characteristics was assessed. The results indicate that single-layer CFRP reinforcement significantly improves concrete axial compressive strength and stiffness, while double-layer CFRP further optimizes stress distribution and load-bearing capacity. Among the composite FRP reinforcements, the combination with CFRP as the outer layer demonstrated superior performance in enhancing the overall structural integrity. Additionally, numerical analyses of the mechanical behavior of the reinforced structures were conducted using ABAQUS 2023HF2 finite element software, which validated the experimental findings and elucidated the mechanisms by which FRP influences the internal stress field of concrete. This research provides theoretical support and empirical data for the optimized design and practical application of FRP reinforcement technologies in engineering. [ABSTRACT FROM AUTHOR]

Nucleic acids are major structures detected by the innate immune system. Although intracellular single-stranded DNA (ssDNA) accumulates during pathogen infection or disease, it remains unclear whether and how intracellular ssDNA stimulates the innate immune system. Here, we report that intracellular ssDNA triggers cytokine expression and cell death in a CGT motif–dependent manner. We identified Schlafen 11 (SLFN11) as an ssDNA-activated RNase, which is essential for the innate immune responses induced by intracellular ssDNA and adeno-associated virus infection. We found that SLFN11 directly binds ssDNA containing CGT motifs through its carboxyl-terminal domain, translocates to the cytoplasm upon ssDNA recognition, and triggers innate immune responses through its amino-terminal ribonuclease activity that cleaves transfer RNA (tRNA). Mice deficient in Slfn9, a mouse homolog of SLFN11, exhibited resistance to CGT ssDNA–induced inflammation, acute hepatitis, and septic shock. This study identifies CGT ssDNA and SLFN11/9 as a class of immunostimulatory nucleic acids and pattern recognition receptors, respectively, and conceptually couples DNA immune sensing to controlled RNase activation and tRNA cleavage. Editor's summary: Single-stranded DNA (ssDNA) generated during microbial infection and in response to DNA damage activates innate immune signaling. Toll-like receptor 9 senses endosomal ssDNA, but whether a designated pattern recognition receptor (PRR) detects ssDNA in other intracellular compartments remains unclear. By screening a library of ssDNA mimics, Zhang et al. identified CGT motifs as immunostimulatory sequences in intracellular ssDNA that lead to cell death and cytokine transcription. After a genome-wide CRISPR-Cas9 screen, they found that SLFN11 (encoding Schlafen 11) and its murine homolog Slfn9 bind CGT ssDNA and activate innate immune responses via the amino-terminal ribonuclease domain. Together, these results demonstrate that Schlafen 11 can function as a PRR for intracellular ssDNA. —Claire Olingy [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Patients with AF have up to seven-fold higher risk of suffering from ischemic stroke. Better understanding of etiologies of AF and its thromboembolic complications are required for improved patient care, as current anti-arrhythmic therapies have limited efficacy and off target effects. Accumulating evidence has implicated a potential role of oxidative stress in the pathogenesis of AF. Excessive production of reactive oxygen species (ROS) is likely involved in the structural and electrical remodeling of the heart, contributing to fibrosis and thrombosis. In particular, NADPH oxidase (NOX) has emerged as a potential enzymatic source for ROS production in AF based on growing evidence from clinical and animal studies. Indeed, NOX can be activated by known upstream triggers of AF such as angiotensin II and atrial stretch. In addition, treatments such as statins, antioxidants, ACEI or AT1RB have been shown to prevent post-operative AF; among which ACEI/AT1RB and statins can attenuate NOX activity. On the other hand, detailed molecular mechanisms by which specific NOX isoform(s) are involved in the pathogenesis of AF and the extent to which activation of NOX plays a causal role in AF development remains to be determined. The current review discusses causes and consequences of oxidative stress in AF with a special focus on the emerging role of NOX pathways.

A new SARS animal model was established by inoculating SARS coronavirus (SARS-CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5-60 after virus inoculation. All eight animals showed a transient fever 2-3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS-CoV-specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS-CoV RNA could be detected in pharyngeal swab samples using nested RT-PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS-CoV-related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS.