Controlling the graphite-like microcrystalline structure of lignin-based ultrafine carbon fibers via the design of condensed structures.

Obtaining lignin-based graphite-like microcrystallites at a relatively low carbonization temperature is still very challenging. In this work, we report a new method based on condensed structures, for regulating graphite-like microcrystalline structures via the incorporation of 4,4'-diphenylmethane diisocyanate (MDI) into the main structure of lignin. The effects of MDI on the thermal properties of lignin and the graphite-like microcrystalline structure of lignin-based ultrafine carbon fibers were extensively studied and investigated. The incorporation of MDI decreased the thermal stability of lignin, increased the carbon yield and enhanced the formation of graphite-like microcrystallites, which are beneficial for reducing energy consumption during the preparation of lignin-based carbon fibers. The modified lignin-based ultrafine carbon fibers (M-LCFs) demonstrated satisfactory electrochemical performance, including high specific capacitance, low charge transfer resistance, and good cycle performance. The M-LCFs-3/2 electrode had a specific capacitance of 241.3 F g-1 at a current density of 0.5 A g-1, and a residual ratio of 90.2 % after 2000 charge and discharge cycles. This study provides a new approach to control the graphite-like microcrystalline structure and electrochemical performance while also optimizing the temperature.

Contributions to the Knowledge of Nemognathinae (Coleoptera: Meloidae) from China.

Despite being the most widespread blister beetle subfamily, Nemognathinae is unfairly understudied in China. In this study, a new genus and species, Sinostenoria yangi Pan, from northern China is described and illustrated. The antennae, elytra, hind wings, and claws of the new genus form a truly unique set of characteristics never observed in other genera of Nemognathini Laporte de Castelnau, 1840. Three species from China are newly recorded and illustrated: Megatrachelus sibiricus (Tauscher, 1812), Zonitomorpha dollei (Fairmaire 1889), and Stenodera djakonovi Aksentjev, 1978. The genus Oreomeloe Tan, 1981, is transferred from the tribe Meloini Gyllenhal, 1910, to Nemognathini based on an examination of the types. Aiming to test the morphology-based placement of the new genus, we conducted molecular phylogenetic analyses using two mitochondrial (COI, 16S) and three nuclear markers (28S, CAD, ITS2). The results confirm our tribal assignment of the new genus and support a clade that consists of Sinostenoriagen. n., Longizonitis Pan and Bologna, 2018, Stenoria cf. grandiceps, and Ctenopus cf. persicus.

A simple chemiluminescent method for the quantification of exosomes based on horseradish peroxidase adsorbed on two-dimensional nanomaterials.

The development of simple methods for the isolation and quantification of exosomes in biological samples is important. By using the typical two-dimensional (2D) nanomaterials, graphene oxide (GO), the present work first studied the interaction of liposomes with the nanocomposites formed by adsorbing HRP on the GO surface and found the presence of liposomes led to the release of HRP from the GO surface to the solution phase triggering the luminol-H2O2 chemiluminescence (CL) reaction to emit light. Benefiting from the similarity of exosomes to liposomes in both composition and morphology aspects, the GO-HRP nanocomposites with a mass ratio of 120:1 and 160:1 were employed for the quantitative detection of exosomes in 100-fold diluted serum samples. The whole detection process took about 15 min and as low as 3.2 × 102 particles µL-1 of exosomes could be sensitively detected. In addition to GO-HRP nanocomposites, the CL responses of other nanocomposites obtained from adsorbing HRP on other 2D nanomaterials such as layered MoS2 for exosomes were also tested. MoS2-HRP exhibited similar behavior and the LODs for the detection of exosomes were 5.8 × 102 particles µL-1. The proposed assays were a biomarker-independent quantitative method that achieved the quantification of exosomes in serum samples directly without an isolation process.

Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis.

The limitations of conventional urine culture methods can be avoided by using culture-independent approaches like polymerase chain reaction (PCR) and next-generation sequencing (NGS). However, the efficacy of these approaches in this setting is still subject to contention. PRISMA-compliant searches were performed on MEDLINE/PubMed, EMBASE, Web of Sciences, and the Cochrane Database until March 2023. The included articles compared PCR or NGS to conventional urine culture for the detection of urinary tract infections (UTIs). RevMan performed meta-analysis, and the Cochrane Risk of Bias Assessment Tool assessed study quality. A total of 10 selected studies that involved 1,291 individuals were included in this meta-analysis. The study found that PCR has a 99% sensitivity and a 94% specificity for diagnosing UTIs. Furthermore, NGS was shown to have a sensitivity of 90% for identifying UTIs and a specificity of 86%. The odds ratio (OR) for PCR to detect Gram-positive bacteria is 0.50 (95% confidence interval [CI] 0.41-0.61), while the OR for NGS to detect Gram-negative bacteria is 0.23 [95% CI 0.09-0.59]. UTIs are typically caused by Gram-negative bacteria like Escherichia coli and Gram-positive bacteria like Staphylococci and Streptococci. PCR and NGS are reliable, culture-free molecular diagnostic methods that, despite being expensive, are essential for UTI diagnosis and prevention due to their high sensitivity and specificity.

Portable fluorescent lateral flow assay for ultrasensitive point-of-care analysis of acute myocardial infarction related microRNA.

Point-of-care quantitative analysis of tracing microRNA disease-biomarkers remains a great challenge in the clinical diagnosis. In this paper, we developed a portable fluorescent lateral flow assay for ultrasensitive quantified detection of acute myocardial infarction related microRNAs in bio-samples. SiO2@DQD (bilayer quantum dots assembly with SiO2 core) based fluorescent lateral flow strip was fabricated as the analysis tool. In order to quantify the tracing microRNA in biosamples, a catalytic hairpin assembly and CRISPR/Cas12a cascade amplification method was performed and combined with the fabricated SiO2@DQD lateral flow strip. Thus, our platform gathered double advantages of portability and ultrasensitive quantification. Based on our strips, target myocardial biomarker microRNA-133a can be detected with a detection limit of 0.32 fM, which was almost 1000-fold sensitive compared with previous reported microRNAs-lateral flow strips. Significantly, this portable fluorescent strip can directly detect microRNAs in serum without any pretreatment and PCR amplification steps. When spiked in serum samples, a recovery of 99.65 %-102.38 % can be obtained. Therefore, our method offers a potential tool for ultrasensitive quantification of diseases related microRNA in the point-of-care diseases diagnosis field.

Major depressive disease research in BRICS: A bibliometric analysis of publications from 2003 to 2022.

Major depressive disorder (MDD) seriously threatens human health. BRICS, known as an acronym for "Brazil, Russia, India, China, and South Africa," were also actively carrying out researches on MDD. This study aimed to conduct a bibliometric study of research on MDD conducted by the BRICS. By searching in the Web of Science and using the software Vosviewer and Citespace as analysis tools, this study analyzed the cooperation network at the country, institution, author-specific levels, the research hotspots and trends from BRICS between 2003-2022. A total of 10,911 articles were finally included. Our findings showed that researches on MDD from BRICS rapidly increased during the past two decades. China and India have shown explosive growth, while South Africa has the largest average "Usage Count" and "Time Cited". The current cooperation partners of the BRICS were mainly high-income countries and other developing countries with similar cultures, languages, and geographical locations. Institutions in high-income countries served as the main bridges for BRICS cooperation, while at the author level, some core authors in the BRICS countries serve as centers. China showed a flexible model in domestic partnership, but institutions and authors in the other four countries have gathered to cooperate within the group. BRICS research on MDD mainly focused on cognitive science, brain science, epidemiology, and disease mechanisms. The keywords"gut microbiota", "network analysis," "machine learning" and "sleep quality" showed explosive growth and might become research hotspots in the near future. This bibliometric analysis provided a science knowledge graph and references for other researchers.

Decoding the spatiotemporal regulation of transcription factors during human spinal cord development.

The spinal cord is a crucial component of the central nervous system that facilitates sensory processing and motor performance. Despite its importance, the spatiotemporal codes underlying human spinal cord development have remained elusive. In this study, we have introduced an image-based single-cell transcription factor (TF) expression decoding spatial transcriptome method (TF-seqFISH) to investigate the spatial expression and regulation of TFs during human spinal cord development. By combining spatial transcriptomic data from TF-seqFISH and single-cell RNA-sequencing data, we uncovered the spatial distribution of neural progenitor cells characterized by combinatorial TFs along the dorsoventral axis, as well as the molecular and spatial features governing neuronal generation, migration, and differentiation along the mediolateral axis. Notably, we observed a sandwich-like organization of excitatory and inhibitory interneurons transiently appearing in the dorsal horns of the developing human spinal cord. In addition, we integrated data from 10× Visium to identify early and late waves of neurogenesis in the dorsal horn, revealing the formation of laminas in the dorsal horns. Our study also illuminated the spatial differences and molecular cues underlying motor neuron (MN) diversification, and the enrichment of Amyotrophic Lateral Sclerosis (ALS) risk genes in MNs and microglia. Interestingly, we detected disease-associated microglia (DAM)-like microglia groups in the developing human spinal cord, which are predicted to be vulnerable to ALS and engaged in the TYROBP causal network and response to unfolded proteins. These findings provide spatiotemporal transcriptomic resources on the developing human spinal cord and potential strategies for spinal cord injury repair and ALS treatment.

Barriers to and Facilitators of the Implementation of a Micronutrient Powder Program for Children: A Systematic Review Based on the Consolidated Framework for Implementation Research.

BACKGROUND: As one of the most cost-effective investments for improving child nutrition, micronutrient powder (MNP) has been widely used in many countries to underpin the Sustainable Development Goals, yet challenges remain regarding its implementation on a large scale. However, few studies have explored the factors that facilitate or impede the implementation process using implementation science theories and frameworks. To address this gap, we adopted the Consolidated Framework of Implementation Research (CFIR) and conducted a systematic review of studies on the implementation barriers to and facilitators of MNP interventions. METHOD: Five publication databases, including EMBASE, Medline, PubMed, Web of Science, and Scopus, were searched for studies on the influencing factors of MNP interventions. Based on the CFIR framework, the facilitators and barriers for the MNP program implementation reported in the included studies were extracted and synthesized by five domains: intervention characteristics, outer setting, inner setting, individual characteristics, and process. RESULTS: A total of 50 articles were eligible for synthesis. The majority of the studies were conducted in lower-middle-income countries (52%) through the free delivery model (78%). The inner setting construct was the most prominently reported factor influencing implementation, specifically including available resources (e.g., irregular or insufficient MNP supply), structural characteristics (e.g., public-driven community-based approach), and access to information and knowledge (e.g., lack of training for primary-level workers). The facilitators of the engagement of private sectors, external guidelines, and regular program monitoring were also highlighted. On the contrary, monotonous tastes and occasional side effects impede intervention implementation. Additionally, we found that the inner setting had an interrelation with other contributing factors in the MNP program implementation. CONCLUSION: Our results suggest that MNP program implementation was prominently influenced by the available resources, organizational structure, and knowledge of both providers and users. Mobilizing local MNP suppliers, engaging public-driven free models in conjunction with market-based channels, and strengthening the training for primary-level health workers could facilitate MNP interventions.

Molecular pathogenesis, mechanism and therapy of Cav1 in prostate cancer.

Prostate cancer is the second incidence of malignant tumors in men worldwide. Its incidence and mortality are increasing year by year. Enhanced expression of Cav1 in prostate cancer has been linked to both proliferation and metastasis of cancer cells, influencing disease progression. Dysregulation of the Cav1 gene shows a notable association with prostate cancer. Nevertheless, there is no systematic review to report about molecular signal mechanism of Cav1 and drug treatment in prostate cancer. This article reviews the structure, physiological and pathological functions of Cav1, the pathogenic signaling pathways involved in prostate cancer, and the current drug treatment of prostate cancer. Cav1 mainly affects the occurrence of prostate cancer through AKT/mTOR, H-RAS/PLCε, CD147/MMPs and other pathways, as well as substance metabolism including lipid metabolism and aerobic glycolysis. Baicalein, simvastatin, triptolide and other drugs can effectively inhibit the growth of prostate cancer. As a biomarker of prostate cancer, Cav1 may provide a potential therapeutic target for the treatment of prostate cancer.

The priority areas and possible pathways for health cooperation in BRICS countries.

As one of the largest alliances of middle-income countries, the BRICS, known as an acronym for five countries including "Brazil, Russia, India, China, and South Africa", represents half of the global population. The health cooperation among BRICS countries will benefit their populations and other middle- and low-income countries. This study aims to summarize the current status of health cooperation in BRICS countries and identify opportunities to strengthen BRICS participation in global health governance. A literature review was conducted to analyze the status, progress, and challenges of BRICS' health cooperation. Content analysis was used to review the 2011-2021 annual joint declarations of the BRICS Health Ministers Meetings. The priority health areas were identified through segmental frequency analysis. Our research suggested that communicable diseases, access to medicine, and universal health coverage appeared most frequently in the content of declarations, indicating the possible top health priorities among BRICS' health collaboration. These priority areas align with the primary health challenges of each country, including the threats of double burden of diseases, as well as the need for improving health systems and access to medicines. Respective external cooperation, inter-BRICS health cooperation, and unified external cooperation are the main forms of health cooperation among BRICS countries. However, challenges such as the lack of a unified image and precise position, lack of practical impact, and weak discourse power have impeded the impact of BRICS on health governance. This study suggests that the BRICS countries should recognize their positioning, improve their unified image, and establish cooperative entities; at the same time, they should increase their practical strength, promote non-governmental cooperation, and expand the cooperation space through the "BRICS Plus" mechanism with countries with similar interests to join.

Apelin-13 protects against cisplatin-induced ototoxicity by inhibiting apoptosis and regulating STAT1 and STAT3.

The ototoxic side effect of cisplatin is a main cause of sensorineural hearing loss. This side effect limits the clinical application of cisplatin and affects patients' quality of life. This study was designed to investigate the effect of apelin-13 on cisplatin-induced C57BL/6 mice hearing loss model and explore the potential underlying molecular mechanisms. Mice were intraperitoneally injected with 100 µg/kg apelin-13 2 h before 3 mg/kg cisplatin injection for 7 consecutive days. Cochlear explants cultured in vitro were pretreated with 10 nM apelin-13 2 h prior to 30 µM cisplatin treatment for another 24 h. Hearing test and morphology results showed that apelin-13 attenuated cisplatin-induced mice hearing loss and protected cochlear hair cells and spiral ganglion neurons from damage. In vivo and in vitro experimental results showed that apelin-3 reduced cisplatin-induced apoptosis of hair cells and spiral ganglion neurons. In addition, apelin-3 preserved mitochondrial membrane potential and inhibited ROS production in cultured cochlear explants. Mechanistic studies showed that apelin-3 decreased cisplatin-induced cleaved caspase 3 expression but increased Bcl-2; inhibited the expression of pro-inflammatory factors TNF-a and IL-6; and increased STAT1 phosphorylation but decreased STAT3 phosphorylation. In conclusion, our results indicate that apelin-13 could be a potential otoprotective agent to prevent cisplatin-induced ototoxicity by inhibiting apoptosis, ROS production, TNF-α and IL-6 expression, and regulating phosphorylation of STAT1 and STAT3 transcription factors.

China's innovation and research contribution to combating neglected diseases: a secondary analysis of China's public research data.

BACKGROUND: Many emerging and developing economies, such as China, have played the important roles in combating global neglected diseases (NDs). This study aims to explore China's public landscape of research projects and funding of NDs and to provide empirical evidence on promoting China's participation in addressing global health priorities that disproportionately affect developing countries. METHODS: We systematically sourced China's public funding information from the National Natural Science Foundation of China and provincial science and technology agency websites up to August 16, 2019. Following the G-FINDER R&D scope, we screened projects of NDs for analysis. National-funded projects were reviewed on an annual basis for exploring the trends and distribution of funding flows. Information on provincial-funded projects was compared with national projects by disease, research type, and geographical distribution. RESULTS: A total of 1266 projects were included for analysis and categorized by year, funding source, recipient, disease, research type, region, and province. China's national public funding for ND research reached a historical peak of USD 16.22 million in 2018. But the proportion of ND research to all public-funded projects was less than 0.5%, and over half of the ND projects were allocated to "the big three," i.e., tuberculosis, HIV/AIDS, and malaria. About 58% of national and provincial ND projects focus on basic research. Economically developed regions and municipalities play dominant roles in leading national ND research, such as Beijing, Shanghai, and Guangdong. Provincial ND projects are primarily driven by endemic regions. CONCLUSIONS: As a new emerging high-tech innovator, China has gradually increased public input to ND-related innovation and research. But there is still a large funding gap among NDs that requires China's increased support and participation. National development plans and cooperative health needs should be taken into account for China's participation in promoting global research and development (R&D) for combating NDs.

Access to DTP-Based Combination Vaccines in Asia-Pacific Countries between 2019 and 2022.

The Asia-Pacific countries are highly diverse in health and economic conditions that may impact vaccine access and uptake. Our study aimed to characterize patterns of health access to DTP-based combination vaccines in 10 countries from 2019 to 2022 using the IQVIA-MIDAS database. The availability, affordability, and accessibility were compared across countries by national health and economic performance indicators using Spearman's rank correlation coefficient. Our findings showed that the three aspects of access to DTP-based vaccines varied substantially in the Asia-Pacific region, with higher levels in countries with better health and economic performance. Affected by the COVID-19 pandemic, vaccine accessibility fluctuates significantly in lower-income countries, with DTP coverage rates falling by more than 14% in the Philippines and Indonesia between 2019 and 2021. For availability and affordability, Singapore and Malaysia from high-income groups were largely affected, which may be related to health expenditure as a percentage of gross domestic product (Coefficient = 0.39, p = 0.03). Our study indicates that greater attention needs to be paid to national health expenditure and routine immunization services to improve vaccine disparities and increase the robustness and resilience of the vaccine supply chain during public health emergencies.

Improving Innovation and Access to Combination Vaccines for Childhood Immunization in China.

BACKGROUND: combination vaccines can improve timely vaccination coverage and mitigate the social and economic burdens of both caregivers and health systems. Compared to other countries with high immunization performance, China remains behind the curve in promoting the inclusion of new combination vaccines into national vaccination schedules. The domestic research and development pipeline faces many technical obstacles, regulatory pressures, and competitive opposition. In addition to this, health disparities regarding combination vaccines exist in each dimension of access and their determinants, including availability, accessibility, acceptability, and quality. Our study aims to provide a cross-disciplinary analysis of China's combination vaccines (from innovation to access) and identify the main factors that affect the attitudes and behavior choices for combination vaccines. METHOD: systematic reviews and secondary data analysis will be conducted to map the landscape of combination vaccines in China and the determinants influencing their innovation and access. A cross-sectional survey will be performed in seven provinces of China based on geo-economic representativeness among caregivers with children that are between 2 and 24 months old and are registered in the national immunization system. Questionnaires will be used to examine the relationship between each dimension of access and their determinants. These questionnaires will cover the caregivers' knowledge, attitude, and willingness to pay for combination vaccines, as well as their perceptions about vaccination services. Semi-structured interviews with the suppliers (public and private) and healthcare providers will help identify research gaps and the key challenges they face when developing and introducing combination vaccines in China. DISCUSSION: using a combined approach, with cross-country and multi-disciplinary support from experts, our research is designed to fill the information gaps in China's combination vaccine industry across the innovation-access spectrum. It will lead to evidence-based recommendations which will foster greater access to innovation-enhancing combination vaccines for childhood immunization in China. Moreover, the multi-dimensional approach could also be adapted beyond combination vaccines to assess innovation and other public goods for health among disadvantaged groups in the future.

Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs. However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000 single-nucleus transcriptomes of the lung, liver, kidney, and cerebral cortex in rhesus macaques ( Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multi-organ dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019 (COVID-19). Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway, which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy (an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection, which may facilitate the development of therapeutic interventions for COVID-19.

Research and development of traditional medicines in low- and middle-income countries: A case study of artemisinin discovery in China.

Though traditional medicines have been developed through practice for thousands of years, limited research has discussed the research and development (R&D) pattern of traditional medicines. China's discovery of artemisinin accumulated valuable experiences to explore traditional medicine under low-resource settings. With limited R&D resources, China mobilized all domestic research units at different levels and departments to develop artemisinin collaboratively. The discovery of artemisinin not only based on valuable experiential wisdom of traditional medicine, but also relied on excellent synergy among all units. In this study, we reviewed the story of how artemisinin was discovered in China, summarized key factors for new drug development from traditional medicines under limited resources, and raised suggestions to utilize traditional medicines in low- and middle-income countries. This case suggested that the vitality of traditional medicine could be extended by promoting new drug development based on modern methods and collaboration.

Priorities of China's participation in global malaria elimination: the perspective of malaria endemic countries.

BACKGROUND: Malaria is one of the major diseases affecting global health, while progress in malaria control and elimination has stagnated in some endemic countries. China has been certificated malaria free by World Health Organization in 2021, and will get more involved on global malaria elimination. Further discussion is needed on how to collaborate with the malaria endemic countries and provide effective help. This study was to investigate the perceptions of malaria endemic countries on China's contribution to global malaria elimination and to lay a foundation for further action. METHODS: Semi-structured interviews were conducted with key informants including national malaria project managers and technicians from malaria endemic countries. Thematic framework approach was used to analyze the data. RESULTS: Malaria endemic countries now face challenges in insufficient funds, technique, products, public health systems and inadequacy of international assistance. They hold a positive attitude towards cooperation with China and identified experience and technique exchange, personnel training, system building and scientific research cooperation as prioritized areas. CONCLUSIONS: China could make full use of its own advantages in technique transfer, health system improvement, information system construction, and health human resource training and take an active part in global malaria elimination.

Drug research and development opportunities in low- and middle-income countries: accelerating traditional medicine through systematic utilization and comprehensive synergy.

BACKGROUND: Though the utilization of traditional medicine has been proposed for modern drug research and development (R&D), limited research has discussed its feasible paths. In this commentary, we summarized key factors for new drug R&D under limited resources by reviewing China's discovery of artemisinin, and raised suggestions to utilize traditional medicines in low- and middle-income countries (LMICs). MAIN TEXT: We suggested that systematic utilization of traditional medicine, outstanding synergy of research units at all levels and timely information-sharing mechanism should be achieved to establish a comprehensive and efficient R&D system, especially under low-resource settings. In the case of artemisinin discovery, Chinese scientists integrated documented traditional medicine experiences and modern approaches to develop drug candidates timely. Due to limited R&D resources, China adopted a collaborative way, motivating nearly all domestic research units at different levels, to develop antimalarial products. Moreover, the excellent synergy among all units through efficient information-sharing mechanisms greatly avoided work repetition and accelerated the R&D process. CONCLUSION: Traditional medicines inspires drug discoveries in LMICs, while a comprehensive and efficient R&D system could accelerate its R&D process and save investment. The discovery of artemisinin in China gave a reliable pattern to promote sustainable development of traditional medicines and a good example to realize R&D of traditional medicine under low-resource settings.