Search

The coronavirus disease 2019 (COVID-19) pandemic, which caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to a crisis with devastating disasters to global public economy and health. Several studies suggest that the SARS-CoV-2 nucleocapsid protein (N protein) is one of uppermost structural constituents of SARS-CoV-2 and is relatively conserved which could become a specific diagnostic marker. In this study, eight single domain antibodies recognized the N protein specifically which were named pN01–pN08 were screened using human phage display library. According to multiple sequence alignment and molecular docking analyses, the interaction mechanism between antibody and N protein was predicted. ELISA results indicated pN01–pN08 with high affinity to protein N. To improve their efficacy, two fusion proteins were prepared and their affinity was tested. These finding showed that fusion proteins had higher affinity than single domain antibodies and will be used as diagnosis for the pandemic of SARS-CoV-2.

Abstract Biofuels are renewable alternatives to fossil fuels. Levopimaric acid‒base biofuels have attracted increasing attention. However, their stability remains a critical issue in practice. Thus, there is a strong impetus to evaluate the thermal stability of levopimaric acid. Through thermogravimetry (TG) and a custom-designed mini closed pressure vessel test (MCPVT) operating under isothermal and stepped temperature conditions, we investigated thermal oxidation characteristics of levopimaric acid under oxygen atmosphere. Thin-layer chromatography (TLC) and iodimetry were used to measure the hydrogen peroxides generated by levopimaric acid oxidation. A high pressure differential scanning calorimeter (HPDSC) was used to assess hydroperoxide thermal decomposition characteristics. Gas chromatography-mass spectrometry (GC-MS) was used to characterize the oxidation products. The thermal decomposition kinetics of levopimaric acid were thus elucidated, and a high peroxide value was detected in the levopimaric acid. The decomposition heat (QDSC) and exothermic onset temperature (Tonset) of hydroperoxides were 338.75 J g−1 and 375.37 K, respectively. Finally, levopimaric acid underwent a second-stage oxidation process at its melt point (423.15 K), resulting in complex oxidation products. Thermal oxidation of levopimaric acid could yield potential thermal hazards, indicating that antioxidants must be added during levopimaric acid application to protect against such hazardous effects.

The hybrid AC/DC microgrid is an independent and controllable energy system that connects various types of distributed power sources, energy storage, and loads. It offers advantages such as a high power quality, flexibility, and cost effectiveness. The operation states of the microgrid primarily include grid-connected and islanded modes. The smooth switching between these two states is a key technology for ensuring the flexible and efficient operation of the microgrid. In this paper, the typical structure of an AC–DC hybrid microgrid and its coordination control strategy are introduced, and an improved microgrid model is proposed. Secondly, an adaptive current–voltage–frequency integrated control method based on signal compensation is proposed to solve the impulse current and voltage generated during the switching between a grid-connected state and an off-grid state. Finally, in response to unplanned grid-connected scenarios, an improved pre-synchronization control strategy based on BP neural networks is introduced to rapidly restore stable operation. The proposed control strategies enhanced the steady-state and transient stability of the hybrid wind–solar–energy storage AC/DC microgrid, achieving seamless grid-connected and islanded transitions without disturbances. The simulation and experimental results validated the correctness and effectiveness of the proposed theories.

Diabetic nephropathy the main reason for end stage renal disease is a common microvascular complication in patients with type 1 and type 2 diabetes. The interleukin-6 (IL-6), acting as a pleiotropic cytokine, play key roles in main autoimmune disorders. The recombinant anti-IL-6R fusion proteins (VHH-0031) constructed and obtained in our lab is a dual target-directed single domain-based fusion protein against the interleukin-6 receptor. This study aims to explore the renoprotective effect of VHH-0031 in diabetic nephropathy. VHH-0031 treatment alleviated renal inflammation, morphologic injury and renal insufficiency in both Goto-Kakizaki rats and STZ-induced Sprague Dawley rats. These renoprotective effects of VHH-0031 are associated with alleviating inflammation and suppression of the JAK2/STAT3 signaling pathway. The mesangial cells treated with VHH-0031 exhibited anti-proliferation, anti-inflammation and inactivation of JAK2/STAT3 pathway under high glucose condition. In conclusion, this study demonstrates that VHH-0031 exhibited a potent protective effect in kidney of diabetic rats and its mechanism may be concerned with the inhibition of the IL-6R/JAK2/STAT3 pathway of glomerular mesangial cells.

Abstract Background The Great Famine in China from 1959 to 1961 is recognized as one of the most severe social and public health disasters of the 20th century, with profound long-term impacts on the health of survivors, particularly on their mental health. Early-life malnutrition and psychological trauma are considered to contribute to a range of health issues in adulthood, including depression. Objective This study aims to explore how the experience of the Chinese Great Famine from 1959 to 1961 affects the risk of depressive symptoms among the elderly. Using a mechanism analysis, the study investigates the roles of social support, socioeconomic status, and intergenerational support in this process. Methods Using micro-level individual data from the China Health and Retirement Longitudinal Survey (CHARLS), combined with province-level excess mortality data, this study employs a cohort-based difference-in-differences model to identify the causal effects of the famine experience on depression levels among the elderly. Results The study reveals that experiencing the Great Famine significantly increases the risk of depression among the elderly. This effect is more pronounced among rural residents, those who experienced the famine during adolescence, and in regions less influenced by Confucian culture. The mechanism analysis indicates that diminished social support, lower socioeconomic status, and insufficient intergenerational support are the primary pathways through which the famine experience influences depression levels in the elderly. Conclusions The experience of the Great Famine has exerted a long-term and profound impact on the mental health of the elderly in China, particularly in terms of depression. The findings provide new perspectives on understanding the long-term effects of major historical events on health and offer important empirical evidence for the development of mental health intervention policies for the elderly.

Corylin is an isoflavone derived from Psoralea Fructus with multiple biological activities. However, its biological functions in renal cell carcinoma (RCC) remain unexplored. Our objective in this study was to delve into the activity of corylin in RCC and to analyze the molecular mechanisms of its actions. In this study, we discovered corylin can significantly attenuate cell viability in a dose-dependent manner and enhance drug sensitivity of RCC cells. Corylin suppresses the malignant behaviors of RCC cells both in vitro and in vivo, such as cellular proliferation, self-renewal, migration and invasion, glycolysis and mitochondrial respiration, tumor formation and metastasis. Further studies revealed corylin conducts it suppressive actions through repressing RAGE (Receptor for Advanced Glycation End Products) expression epigenetically, and corylin facilitates the hypermethylation of RAGE promoter. In conclusion, our findings demonstrated the tumor-suppressive role of corylin in RCC and uncovered its novel molecular mechanism for therapeutic effects on RCC treatment.

BackgroundGrassroots center for disease control and prevention (CDC) staff undertake intensive work of disease prevention and control, and may be susceptible to occupational stress, anxiety, depression, and other health problems. ObjectiveTo understand the current situation of occupational stress, anxiety, and depression among grassroots CDC staff, and to identify potential risk factor configurations for occupational stress, anxiety, and depression using fuzzy set qualitative comparative analysis (fsQCA), so as to provide a basis for effective intervention. MethodsThe staff working in county/district-level CDCs in Hebei Province were the target population of the current study. Stratified random cluster sampling method was used to select 1860 staff members of the target population. A questionnaire of general situation, Job Content Scale, 7-item Generalized Anxiety Disorder Scale, and Patient Health Questionnaire-9 were used. Risk factor configurations associated with health outcomes of interest were identified by fsQCA3.0 software. ResultsThe positive rates of occupational stress, anxiety, and depression were 42.69%, 44.25%, and 47.96%, respectively. Marital status was a necessary condition for occupational stress, anxiety, and depression in the grassroots CDC staff (the necessity values were 0.911, 0.939, and 0.933, respectively). There were two types of risk factor configurations for occupational stress: "self-improvement" and "disease burden"; the risk factor configurations for anxiety were "disease burden" and "economic-disease burden"; while the risk factor configurations for depression were "disease burden", "economic-disease burden", and "self-improvement". The overall consistency scores of occupational stress, anxiety, and depression were 0.941, 0.820, and 0.774, respectively. Regarding outstanding components, "self-improvement" included pressure of job requirements and promotion, "disease burden" included impact of chronic illness on psychological state, and "economic-disease burden" included not only impact of chronic illness but also financial support for CDC staff. ConclusionAll positive rates of occupational stress, anxiety, and depression are high among grassroots CDC staff in Hebei Province. Occupational stress, anxiety, and depression of grassroots CDC staff are the results of multiple influencing factors, so targeted intervention measures should be formulated.

The currently used anti-cytokine therapeutic antibodies cannot selectively neutralize pathogenic cytokine signaling that cause collateral damage to protective signaling cascades carrying the potential for unwanted side effects. The variable domains of heavy-chain only antibodies (HCAbs) discovered in Camelidae are stable and display to be fully functional in antigen-binding against variable targets, which seem to be attractive candidates for the next-generation biologic drug study. The purpose of our study was to establish a simple prokaryotic expression system for large-scale expression, purification, and refolding of the recombinant anti-tumor necrosis factor a (TNF-a) fusion protein (FVH1-1) from inclusion bodies. Over 95% purity of the recombinant anti-TNF-a fusion proteins was obtained by just one purification step in our developed prokaryotic expression system, while the results of surface plasmon resonance (SPR) established the high-efficiency potent binding ability of FVH1-1 to human TNF-a. The counteraction of TNF-a cytotoxic effect experiment on the mouse fibroblast fibrosarcoma cell line (L929) confirmed that the expressed FVH1-1 were able to selectively and highly combine with human recombinant TNF-a (hTNF-a) in vitro. Western blot results showed that FVH1-1 can inhibit the activation of caspase-9 and PARP, which are the apoptotic signaling pathway proteins activated by hTNF-a. Meanwhile, lysosome autophagy signaling pathways stimulated by hTNF-a were inhibited by FVH1-1, which down-regulated the expression of LC3II/LC3I and up-regulated the expression of P62, indicating that the autophagy linked with TNF-a-induced apoptosis in response to rheumatoid arthritis. The results of the AIA rat model experiment presented that FVH1-1 can reduce the degree of joint swelling and inflammatory factors to a certain extent in vivo. [ABSTRACT FROM AUTHOR]

Bacteria have evolved proteinaceous microcompartments (BMCs) to control the passage of metabolites and facilitate catabolism in a micro-environment. Here, Yang et al. apply fluorescence microscopy to characterize the protein-protein interaction and assembly involved in the de novo biogenesis of propanediol-utilization (Pdu) metabolosomes and show that Pdu BMCs undergo a combination of ‘Shell first’ and ‘Cargo first’ assembly.

Abstract To construct a multi‐energy complementary system for intelligent building group, a direct control strategy for central air conditioning based on discrete Fourier transform is proposed. This strategy can reduce the deviation between actual load and transaction results while absorbing photovoltaic (PV) power generation and improving the enterprise economy in the power market environment. The strategy uses the discrete Fourier transform (DFT) to find the scheduling demand of the central air‐conditioning (AC) group and realizes the scheduling demand by changing the temperature setting value. Also, the strategy can assess AC status in real‐time, which combines with ultra‐short‐term load forecasting to adjust future purchase planned values. The simulation results show that the strategy can realize a real‐time load track with the power purchase plan while absorbing PV power generation with low action times and temperature changes, which improves the absorption of distributed PV power generation and reduces the assessment bias.

Human-caused nitrogen (N) deposition is a global environmental issue that can change community composition, functions, and ecosystem services. N deposition affects plants, soil, and microorganisms regionally and is linked to ecosystem, soil, and climate factors. We examined the effects of six N addition levels (0, 2.34 g, 4.67, 9.34,18.68, and 37.35 g N m−2 yr−1) on aboveground vegetation, surface soil properties, and microbial community. Alterations in microbial communities in response to N addition were monitored using 16S rRNA (16S ribosomal ribonucleic acid, where S donates a sedimentation coefficient) and ITS (internal transcribed spacer) regions for bacterial and fungal communities, respectively. N addition positively affected aboveground vegetation traits, such as biomass and community weighted mean of leaf nitrogen. N addition also limited phosphorus (P) availability and altered the microbial community assembly process from random processes to deterministic processes. The microbial community diversity and composition, however, were not sensitive to N addition. Partial least squares structural equation models showed that the composition of bacterial communities was mainly driven by the composition of plant communities and total nitrogen, while the composition of fungal communities was driven by soil pH and community weighted mean of leaf nitrogen. Taken together, the results of this research improved our understanding of the response of grassland ecosystems to N deposition and provided a theoretical basis for grassland utilization and management under N deposition.

ALI is a severe inflammatory disease of the lungs. In previous studies, we found that GQD was effective against ALI, but specific molecular mechanism is still unclear. Therefore, this study was to examine effect of GQD on LPS-induced ALI rats and underlying mechanisms using multi-omics and molecular methods. The results showed that GQD significantly improved lung tissue damage, reduced pulmonary edema, inhibited MPO activity, and improved respiratory function in ALI rat. Additionally, GQD significantly reduced the levels of TNF-α, IL-1β, and IL-6 in serum and BALF. Furthermore, metabolomic analysis showed that GQD reduced pulmonary inflammation by improving metabolic remodeling. Moreover, transcriptomic analysis showed that GQD inhibited the activation of complement pathway and regulated Th17 and Treg cells balance. Additionally, GQD inhibited the expression of C3, C5a, and IL-17, and promoted the expression of TGF-β and CYP1A1 at the mRNA and protein levels. Gut microbial assay showed that GQD treatment increased the relative abundance of Firmicutes and their genera in intestinal microbiota, and increased short-chain fatty acids concentration. Overall, GQD treated ALI by improving metabolic remodeling, affecting immune-related pathways and regulating intestinal microbiota. This study provides a solid scientific basis for promoting the clinical use of GQD in treating ALI.

The extreme oxygen sensitive character of hydrogenases is a longstanding issue for hydrogen production in bacteria. Here, the authors build carboxysome shells in E. coli and incorporate catalytically active hydrogenases and functional partners within the empty shell for the production of hydrogen.

Enteric pathogens such as Salmonella depend on propanediol-utilising microcompartments (Pdu MCP), which self-assemble from cytosolic proteins. Using mass spectrometry-based absolute quantification, the authors here define the protein stoichiometry and propose an organizational model of a Salmonella Pdu MCP.

A photoelectrochemical device was achieved by interfacial self-assembly of macrocyclic π-conjugated copper phthalocyanine (CuPc) on surface of TiO2 nanorod arrays (NRs). The photocurrent density of the elegant TiO2@CuPc NRs photoanode reaches 2.40 mA/cm2 at 1.23 V vs. RHE under the illumination of 100 mW/cm2 from AM 1.5G sun simulator, which is 2.4 times higher than that of the pure TiO2. At the same time, the photoelectrochemical device constructed through this strategy has good stability and the photocurrent density remain almost no decline after 8 h of continuous operation. The Mott-Schottky and LSV curves demonstrate that CuPc act as a co-catalyst for water oxidation and a possible mechanism is proposed for water oxidation based on careful analysis of the detailed results. The holes from VB of TiO2 photogenerated by electrons exciting are consumed by a process in which Cu2+ is oxidized to Cu3+ and Cu4+, and then oxidize water to produce oxygen. CuPc species is considered to be a fast redox mediator to reduce the activation energy of water oxidation in and effectively promote charge separation.

Bacterial microcompartments (BMCs) are proteinaceous organelles widespread among bacterial phyla and provide a means for compartmentalizing specific metabolic pathways. They sequester catalytic enzymes from the cytoplasm, using an icosahedral proteinaceous shell with selective permeability to metabolic molecules and substrates, to enhance metabolic efficiency. Carboxysomes were the first BMCs discovered and their unprecedented capacity of CO2 fixation allows cyanobacteria to make a significant contribution to global carbon fixation. There is an increasing interest in utilizing synthetic biology to construct synthetic carboxysomes in new hosts, i.e., higher plants, to enhance carbon fixation and productivity. Here, we report the construction of a synthetic operon of the β-carboxysome from the cyanobacterium Synechococcus elongatus PCC7942 to generate functional β-carboxysome-like structures in Escherichia coli. The protein expression, structure, assembly, and activity of synthetic β-carboxysomes were characterized in depth using confocal, electron and atomic force microscopy, proteomics, immunoblot analysis, and enzymatic assays. Furthermore, we examined the in vivo interchangeability of β-carboxysome building blocks with other BMC components. To our knowledge, this is the first production of functional β-carboxysome-like structures in heterologous organisms. It provides important information for the engineering of fully functional carboxysomes and CO2-fixing modules in higher plants. The study strengthens our synthetic biology toolbox for generating BMC-based organelles with tunable activities and new scaffolding biomaterials for metabolic improvement and molecule delivery.