A full-length glycoprotein mRNA vaccine confers complete protection against severe fever with thrombocytopenia syndrome virus, with broad-spectrum protective effects against bandaviruses.

Highly pathogenic viruses from family Phenuiviridae, which are mainly transmitted by arthropods, have intermittently sparked epidemics worldwide. In particular, tick-borne bandaviruses, such as severe fever with thrombocytopenia syndrome virus (SFTSV), continue to spread in mountainous areas, resulting in an average mortality rate as high as 10.5%, highlighting the urgency and importance of vaccine development. Here, an mRNA vaccine developed based on the full-length SFTSV glycoprotein, containing both the receptor-binding domain and the fusion domain, was shown to confer complete protection against SFTSV at a very low dose by triggering a type 1 helper T cell-biased cellular immune response in rodents. Moreover, the vaccine candidate elicited long-term immunity and protection against SFTSV for at least 5 months. Notably, it provided complete cross-protection against other bandaviruses, such as the Heartland virus and Guertu virus, in lethal challenge models. Further research revealed that the conserved epitopes among bandaviruses within the full-length SFTSV glycoprotein may facilitate broad-spectrum protection mediated by the cellular immune response. Collectively, these findings demonstrate that the full-length SFTSV glycoprotein mRNA vaccine is a promising vaccine candidate for SFTSV and other bandaviruses, and provide guidance for the development of broad-spectrum vaccines from conserved antigens and epitopes. IMPORTANCE: Tick-borne bandaviruses, such as SFTSV and Heartland virus, sporadically trigger outbreaks in addition to influenza viruses and coronaviruses, yet there are no specific vaccines or therapeutics against them. mRNA vaccine technology has advantages in terms of enabling in situ expression and triggering cellular immunity, thus offering new solutions for vaccine development against intractable viruses, such as bandaviruses. In this study, we developed a novel vaccine candidate for SFTSV by employing mRNA vaccination technology and using a full-length glycoprotein as an antigen target. This candidate vaccine confers complete and durable protection against SFTSV at a notably low dose while also providing cross-protection against Heartland virus and Guertu virus. This study highlights the prospective value of full-length SFTSV-glycoprotein-based mRNA vaccines and suggests a potential strategy for broad-spectrum bandavirus vaccines.

PCDH15 Dual-AAV Gene Therapy for Deafness and Blindness in Usher Syndrome Type 1F.

Usher syndrome type 1F (USH1F), resulting from mutations in the protocadherin-15 (PCDH15) gene, is characterized by congenital lack of hearing and balance, and progressive blindness in the form of retinitis pigmentosa. In this study, we explore a novel approach for USH1F gene therapy, exceeding the single AAV packaging limit by employing a dual adeno-associated virus (AAV) strategy to deliver the full-length PCDH15 coding sequence. We demonstrate the efficacy of this strategy in mouse USH1F models, effectively restoring hearing and balance in these mice. Importantly, our approach also proves successful in expressing PCDH15 in clinically relevant retinal models, including human retinal organoids and non-human primate retina, showing efficient targeting of photoreceptors and proper protein expression in the calyceal processes. This research represents a major step toward advancing gene therapy for USH1F and the multiple challenges of hearing, balance, and vision impairment.

Mapping the scientific research on integrated care: a bibliometric and social network analysis.

Background: Integrated care (IC) is the cornerstone of the sustainable development of the medical and health system. A thorough examination of the existing scientific literature on IC is essential for assessing the present state of knowledge on this subject. This review seeks to offer an overview of evidence-based knowledge, pinpoint existing knowledge gaps related to IC, and identify areas requiring further research. Methods: Data were retrieved from the Web of Science Core Collection, from 2010 to 2020. Bibliometrics and social network analysis were used to explore and map the knowledge structure, research hotspots, development status, academic groups and future development trends of IC. Results: A total of 7,501 articles were obtained. The number of publications on IC was rising in general. Healthcare science services were the most common topics. The United States contributed the highest number of articles. The level of collaboration between countries and between authors was found to be relatively low. The keywords were stratified into four clusters: IC, depression, integrative medicine, and primary health care. In recent years, complementary medicine has become a hotspot and will continue to be a focus. Conclusion: The study provides a comprehensive analysis of global research hotspots and trends in IC, and highlights the characteristics, challenges, and potential solutions of IC. To address resource fragmentation, collaboration difficulties, insufficient financial incentives, and poor information sharing, international collaboration needs to be strengthened to promote value co-creation and model innovation in IC. The contribution of this study lies in enhancing people's understanding of the current state of IC research, guiding scholars to discover new research perspectives, and providing valuable references for researchers and policymakers in designing and implementing effective IC strategies.

Protection of the receptor binding domain (RBD) dimer against SARS-CoV-2 and its variants.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants achieved immune escape and became less virulent and easily transmissible through rapid mutation in the spike protein, thus the efficacy of vaccines on the market or in development continues to be challenged. Updating the vaccine, exploring compromise vaccination strategies, and evaluating the efficacy of candidate vaccines for the emerging variants in a timely manner are important to combat complex and volatile SARS-CoV-2. This study reports that vaccines prepared from the dimeric receptor-binding domain (RBD) recombinant protein, which can be quickly produced using a mature and stable process platform, had both good immunogenicity and protection in vivo and could completely protect rodents from lethal challenge by SARS-CoV-2 and its variants, including the emerging Omicron XBB.1.16, highlighting the value of dimeric recombinant vaccines in the post-COVID-19 era.

Functional cooperation between IKCa and TRPC1 channels regulates serum-induced vascular smooth muscle cell proliferation via mediating Ca2+ influx and ERK1/2 activation.

The increased proliferation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis of vascular diseases. The intermediate conductance calcium-activated potassium (IKCa ) channel plays a critical role in VSMC proliferation by raising the intracellular calcium concentration ([Ca2+ ]i ), but the underlying mechanism is still not unclear. Here we investigated the cooperation between IKCa and transient receptor potential canonical 1 (TRPC1) channels in mediating extracellular Ca2+ entry, which in turn activates downstream Ca2+ signalling in the regulation of VSMC proliferation using serum-induced cell proliferation model. Serum-induced cell proliferation was accompanied with up-regulation of IKCa expression and an increase in [Ca2+ ]i . Serum-induced cell proliferation and increase in [Ca2+ ]i were suppressed by IKCa inhibition with TRAM-34 or IKCa knockdown. Serum-induced cell proliferation was strongly reduced by the removal of extracellular Ca2+ with EGTA or intracellular Ca2+ with BAPTA-AM and, additionally, by TRPC1 knockdown. Moreover, the increase in [Ca2+ ]i induced by serum or by IKCa activation with 1-EBIO was attenuated by TRPC1 knockdown. Finally, serum induced ERK1/2 activation, which was attenuated by treatment with TRAM-34 or BAPTA-AM, as well as TRPC1 knockdown. Consistently, serum-induced cell proliferation was suppressed by ERK1/2 inhibition with PD98059. Taken together, these results suggest that the IKCa and TRPC1 channels cooperate in mediating Ca2+ influx that activates the ERK1/2 pathway to promote cell proliferation, thus providing new mechanistic insights into VSMC proliferation.

Fluorescent and Colorimetric Ionic Probe Based on Fluorescein for the Rapid and On-Site Detection of Paraquat in Vegetables and the Environment.

Detection of pesticide paraquat (PQ) is of considerable significance to ensure food safety, and its rapid and on-site detection is still a challenge. Aimed at the ion characteristics of PQ, an "enrichment and detection" strategy was proposed to improve the sensitivity through electrostatic attractions, and the ion characteristic of probes was adopted to increase the portability through avoiding aggregation-caused quenching effects in the paper strips. Herein, a novel anion-functionalized ionic liquid (IL) probe with a large conjugated plane and rich π-electrons ([Fluo][P66614]2) was designed as a fluorescent and colorimetric dual-channel probe to sensitively and rapidly detect trace amounts of PQ in vegetables and the environment. The proposed probe exhibited good linearity with a detection limit of 64.0 nM in the PQ concentration range of 0.3-7.0 µM (fluorometry) and 0.1 µM in that of 0.1-8.0 µM (colorimetry), respectively. In addition, it displayed a rapid fluorescence quenching response from green to dark (<5 s) and excellent anti-interference (among 23 other pesticides) due to dual effects of electrostatic attraction and π-π stacking. Most importantly, the lipophilic IL probe could be applied in real vegetables and environmental samples with a satisfying recovery rate of 98-103% and assembled into a handy paper strip that achieved the visual semiquantitative detection of PQ. This ionic probe provides a feasible approach for rapidly and conveniently detecting PQ for ensuring agricultural and food safety and opens a new avenue to detect ion-responsive analytes in real complex samples by an "enrichment and detection" strategy.

Can supplementary private health insurance further supplement health.

Background: China advocates a health insurance system with social health insurance (SHI) as the main body and private health insurance (PHI) as the supplement. The study of PHI's complementary role in health is conducive to providing evidence for PHI's policy expansion and encouraging the public to participate in PHI, which is insufficient in China. Methods: We used the three-wave balanced panel data of the China Health and Retirement Longitudinal Survey (CHARLS). Taking the ownership of supplementary PHI as the independent variable and EQ-5D index scores as the dependent variable, the panel instrumental variable (IV) method was used to analyze the impact of participation in PHI on health. We also assessed the heterogeneity of the health effects of PHI between chronic and non-chronic disease groups and between low- and high-income groups. Results: The coverage rate of PHI at baseline was 10.53%. The regression results showed that participating in PHI on the basis of SHI could result in an additional 8.21% health gain (p < 0.001). At the same time, PHI had greater health gain for chronic disease population than for healthy population (9.25 vs. 6.24%, p < 0.001), and greater health gain for high-income population than for low-income population (8.32 vs. 5.31%, p < 0.001). Conclusion: Participating in supplementary PHI can effectively enhance the health status of the insured, and has a more significant effect on patients with chronic diseases. The development of PHI should be further supported, while the health inequality in different income groups should be paid attention to.

Effect of informal care on health care utilisation for the elderly in urban and rural China: evidence from China health and retirement longitudinal study (CHARLS).

BACKGROUND: Receiving informal care from family members is the mainstream way of care for the elderly in China because of the influence of the culture of filial piety. However, the relationship between informal care and health care use in urban and rural areas needs to be further explored. This study aimed to understand the association between informal care and health care utilisation for the elderly and explore how this effect may differ between urban and rural China. METHOD: A total of 5704 residents aged 65 years and above were selected from wave 3 (2015) and wave 4 (2018) of the China Health and Retirement Longitudinal Study, which is a nationally representative survey. A negative binomial regression model for the panel data was used to explore the relationship between informal care and health care utilisation. A fixed-effect binary choice model for panel data was used for the sensitivity test. RESULT: The elderly who received informal care had increased in outpatient and inpatient visits compared with those who did not receive informal care. The inpatient visits of the elderly who received 15-29 days of informal care was higher than the elderly who did not receive informal care (incidence rate ratio [IRR] = 2.082, P < 0.05). Moreover, the elderly who received informal care for more than 30 days had 39.6% more inpatient visits (IRR = 1.396, P < 0.01) and 37.4% more outpatient visits than the elderly who did not receive informal care (IRR = 1.374, P < 0.05). For urban respondents, receiving informal care can facilitate outpatient use of the elderly, but for rural respondents, receiving informal care can predict an increase in outpatient and inpatient visits. CONCLUSION: Informal care was associated with higher use of health services. The association between informal care and health care utilisation varies between rural and urban residents. These findings indicate the role of informal care and remind that relevant departments should pay attention to the differences in medical service utilisation levels amongst different elderly groups.

Oceanobacter mangrovi Sp. Nov., a Novel Poly-ß-hydroxybutyrate Accumulating Bacterium Isolated from Mangrove Sediment.

A Gram-stain-negative, rod-shaped, motile, mesophilic, and aerobic bacterial strain, designated SM2-42 T was isolated from a mangrove sediment. Catalase activity and oxidase activity were positive. Growth was observed at 20 °C-40 °C, pH 6.0-8.0, and in the presence of 0.5-5.0% NaCl. Cells of strain SM2-42 T contained poly-ß-hydroxybutyrate granules. The 16S rRNA gene of strain SM2-42 T had maximum sequence similarity with Oceanobacter kriegii 197 T of 97.1%. Phylogenetic analysis based on 16S rRNA gene sequence and 120 conserved concatenated proteins indicated that strain SM2-42 T was affiliated to the genus Oceanobacter and formed a monophyletic branch with O. kriegii 197 T. The average nucleotide identity and digital DNA-DNA hybridization values between strain SM2-42 T and O. kriegii 197 T were 76.43% and 21.60%, respectively. The major isoprenoid quinone was Q-8. The major fatty acids (> 10%) comprised C16:0, summed feature 8 (C18:1ω7c and C18:1 ω6c), C18:0, and summed feature 3 (C16:1ω7c and/or C16:1 ω6c). The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminolipid and two unidentified lipids. The draft genome size was 5,115,008 bp with DNA G + C content of 54.3%. Based on phylogenetic analyses and whole genomic comparisons, strain SM2-42 T represented a novel species, for which the name Oceanobacter mangrovi sp. nov. was proposed. The type strain was SM2-42 T (= MCCC 1K06300T = KCTC 82938 T).

Flavonoid glycosides from the nectar of Camellia reticulata Lindl.

The nectar of Camellia reticulata Lindl. contains sugar, amino acids and other nutritional components, suggesting that it could be developed for food and food additives. To understand the effects of the nectar on human health, we investigated its chemical constituents. Two new flavonoid glycosides, cameretiins A and B (1 and 2), and two known flavonoid glycosides, kaempferol 3-O-(2''-O-E-p-coumaroyl)-ß-D-glucopyranoside (3) and tiliroside (4) were obtained from the nectar of Camellia reticulata Lindl. Their structures were determined based on analysis of their spectroscopic data and by comparison with 1D NMR spectroscopic data of known compounds reported in the literature. Compounds (1-4) were first isolated from the nectar of Camellia reticulata Lindl.

What intensity of exercise is most suitable for the elderly in China? A propensity score matching analysis.

BACKGROUND: The strategy of successful ageing is an important means to deal with the challenges of the current ageing society. This paper aims to explore the effects of different intensities of physical activity on the successful ageing of the elderly. METHODS: Our data were from wave 4 of the China Health and Retirement Longitudinal Survey (CHARLS), involving 9026 residents aged 60 years and older. The intensity of physical activity was divided into three levels: vigorous, moderate and mild. The concept of successful ageing adopted a four-dimensional model of life satisfaction added to the theoretical model of Rowe and Kahn's. Propensity score matching (PSM) with controlling nine confounding factors were used to analyse the effects of different intensities of physical activity. RESULTS: The percentage of successful ageing was 1.88% among all subjects. Among them, 30.26, 29.57 and 29.40% of the elderly often participated in vigorous, moderate and mild physical activity, respectively. The results of PSM showed that participation in moderate activity increased the probability of successful ageing of the elderly by 0.76-0.78% (P < 0.001), while participation in vigorous and mild physical activity had no significant effect on successful ageing (P > 0.05). Moderate physical activity had statistically significant effects on four components of successful aging, including major disease, physical function, life satisfaction, and social participation (P < 0.05). CONCLUSION: Moderate-intensity physical activity was most beneficial to the successful ageing of the elderly and should be promoted in the elderly population.

Stimulation of vascular smooth muscle cell proliferation by stiff matrix via the IKCa channel-dependent Ca2+ signaling.

Vascular stiffening, an early and common characteristic of cardiovascular diseases (CVDs), stimulates vascular smooth muscle cell (VSMC) proliferation which reciprocally accelerates the progression of CVDs. However, the mechanisms by which extracellular matrix stiffness accompanying vascular stiffening regulates VSMC proliferation remain largely unknown. In the present study, we examined the role of the intermediate-conductance Ca2+ -activated K+  (IKCa ) channel in the matrix stiffness regulation of VSMC proliferation by growing A7r5 cells on soft and stiff polydimethylsiloxane substrates with stiffness close to these of arteries under physiological and pathological conditions, respectively. Stiff substrates stimulated cell proliferation and upregulated the expression of the IKCa channel. Stiff substrate-induced cell proliferation was suppressed by pharmacological inhibition using TRAM34, an IKCa channel blocker, or genetic depletion of the IKCa channel. In addition, stiff substrate-induced cell proliferation was also suppressed by reducing extracellular Ca2+ concentration using EGTA or intracellular Ca2+ concentration using BAPTA-AM. Moreover, stiff substrate induced activation of extracellular signal-regulated kinases (ERKs), which was inhibited by treatment with TRAM34 or BAPTA-AM. Stiff substrate-induced cell proliferation was suppressed by treatment with PD98059, an ERK inhibitor. Taken together, these results show that substrates with pathologically relevant stiffness upregulate the IKCa channel expression to enhance intracellular Ca2+ signaling and subsequent activation of the ERK signal pathway to drive cell proliferation. These findings provide a novel mechanism by which vascular stiffening regulates VSMC function.

Effect of Social Participation on the Physical Functioning and Depression of Empty-Nest Elderly in China: Evidence from the China Health and Retirement Longitudinal Survey (CHARLS).

This study aimed to explore the impact of social participation (SP) on physical functioning and depression among empty-nest elderly taking part in the fourth wave of the China Health and Retirement Longitudinal Survey (CHARLS, 2018). The instrumental variable (IV) method and propensity score matching (PSM) method were used to analyse the impact of SP. The two-stage regression results of the IV method showed that SP has a significant negative impact on the physical functioning scores of empty-nest elderly (ß = -3.539, p < 0.001) and non-empty-nest elderly (ß = -4.703, p < 0.001), and SP has a significant negative impact on the depression scores of empty-nest elderly (ß = -2.404, p < 0.001) and non-empty-nest elderly (ß = -1.957, p < 0.001). The results of the PSM method were basically consistent with the IV method. Compared with non-empty-nest elderly, SP had more positive effects on the depression of empty-nest elderly (Wald χ2 = 6.62, p = 0.010). Providing a friendly and supportive environment for the SP of empty-nest elderly was an important measure to promote healthy ageing. Targeted SP may be one of the greatest opportunities to improve the mental health of empty-nest elderly.

A critical role of the KCa 3.1 channel in mechanical stretch-induced proliferation of rat bone marrow-derived mesenchymal stem cells.

Mechanical stimulation is an important factor regulating mesenchymal stem cell (MSC) functions such as proliferation. The Ca2+ -activated K+ channel, KCa 3.1, is critically engaged in MSC proliferation but its role in mechanical regulation of MSC proliferation remains unknown. Here, we examined the KCa 3.1 channel expression and its role in rat bone marrow-derived MSC (BMSC) proliferation in response to mechanical stretch. Application of mechanical stretch stimulated BMSC proliferation via promoting cell cycle progression. Such mechanical stimulation up-regulated the KCa 3.1 channel expression and pharmacological or genetic inhibition of the KCa 3.1 channel strongly suppressed stretch-induced increase in cell proliferation and cell cycle progression. These results support that the KCa 3.1 channel plays an important role in transducing mechanical forces to MSC proliferation. Our finding provides new mechanistic insights into how mechanical stimuli regulate MSC proliferation and also a viable bioengineering approach to improve MSC proliferation.

High Temperature Induced Glume Closure Resulted in Lower Fertility in Hybrid Rice Seed Production.

Predicted climate changes, in particular, the increased dimension and frequency of heat waves, are expected to affect crop growth in the future seriously. Hybrid rice relies on seed production from male sterile and restorer lines. Experiments were conducted over two consecutive years to compare the high temperature tolerance of parents of different hybrid rice combinations, in terms of fertility rate, flowering pattern, pollination and physiological parameters of the lodicule. Three male sterile lines and a broad compatibility restorer line (as pollen donor and conventional variety as well) were grown to heading stage and then treated with average daily temperatures of 26°C (range 23-30°C), 28°C (25-32°C), and 30°C (26-34°C), respectively, continued for 5-7 days each in a natural light phytotron which simulated the local typical high temperature weather in the field. The results indicated that male sterile lines were more sensitive to high temperature than the restorer line for fertility rate, and the sensitivity varied between varieties. The fertility rate of the restorer line was maintained at about 90% under the high temperature treatments, while it decreased in the male sterile lines by 23.3 and 48.1% at 28 and 30°C, respectively. The fertility rate of the most sensitive line declined by 70%, and the tolerant line declined by 34% at 30°C. Glume closure in the male sterile lines was a major reason for the reduced fertility rate under high temperature, which is closely correlated with carbohydrates content and the vascular bundle pattern in the lodicule. The present study identified a useful trait to select male sterile lines with high temperature tolerance for seed production.

[A study on chilling injury in medicinal plants region of South China Botanical Garden].

From late January to early February in 2008, Guangzhou suffered from the cold and humid rainy for 20 days, and the daily mean temperature was under 10 degrees C. In 794 species of medicinal plants in South China Botanical Garden, 78 species (9.8%) suffered from chilling injury. The reasons were analyzed and some useful suggestions were made.