Microstate-based brain network dynamics distinguishing temporal lobe epilepsy patients: A machine learning approach.

Temporal lobe epilepsy (TLE) stands as the predominant adult focal epilepsy syndrome, characterized by dysfunctional intrinsic brain dynamics. However, the precise mechanisms underlying seizures in these patients remain elusive. Our study encompassed 116 TLE patients compared with 51 healthy controls. Employing microstate analysis, we assessed brain dynamic disparities between TLE patients and healthy controls, as well as between drug-resistant epilepsy (DRE) and drug-sensitive epilepsy (DSE) patients. We constructed dynamic functional connectivity networks based on microstates and quantified their spatial and temporal variability. Utilizing these brain network features, we developed machine learning models to discriminate between TLE patients and healthy controls, and between DRE and DSE patients. Temporal dynamics in TLE patients exhibited significant acceleration compared to healthy controls, along with heightened synchronization and instability in brain networks. Moreover, DRE patients displayed notably lower spatial variability in certain parts of microstate B, E and F dynamic functional connectivity networks, while temporal variability in certain parts of microstate E and G dynamic functional connectivity networks was markedly higher in DRE patients compared to DSE patients. The machine learning model based on these spatiotemporal metrics effectively differentiated TLE patients from healthy controls and discerned DRE from DSE patients. The accelerated microstate dynamics and disrupted microstate sequences observed in TLE patients mirror highly unstable intrinsic brain dynamics, potentially underlying abnormal discharges. Additionally, the presence of highly synchronized and unstable activities in brain networks of DRE patients signifies the establishment of stable epileptogenic networks, contributing to the poor responsiveness to antiseizure medications. The model based on spatiotemporal metrics demonstrated robust predictive performance, accurately distinguishing both TLE patients from healthy controls and DRE patients from DSE patients.

Integrated Metabolomics and Transcriptomics Analysis Reveals New Insights into Triterpene Biosynthesis in Rosa rugosa.

Rosa rugosa is highly regarded for its aesthetic and therapeutic qualities. In particular, R. rugosa's flowers are known to produce essential oils containing a mixture of volatile terpenes, phenylpropanoids, and other compounds. Despite this, extensive research exists on volatile terpenes in flowers, while the knowledge of non-volatile terpenes in distinct tissues is still limited. Using UPLC-ESI-MS/MS, a comprehensive analysis of the terpene metabolites in five different tissues of R. rugosa was conducted. These metabolites accumulated in distinct tissues, and the majority of them were triterpenoids. Transcriptome data were collected from five tissues using RNA-seq. Transcriptomics and metabolomics were utilized to evaluate the triterpene biosynthesis pathway, resulting in new insights into its regulation and biosynthesis. The RrOSC10 was identified as a key enzyme in converting 2,3-oxidosqualene into α-amyrin, potentially contributing to the triterpene biosynthesis pathway. Furthermore, the expression of the RrOSC10 gene was upregulated by salinity for 0.5 h and 1 h, with subsequent downregulation at 2 h. This study lays a foundation for future research on the biosynthesis and accumulation of triterpenes in R. rugosa.

Application of high intensity focused ultrasound combined with nanomaterials in anti-tumor therapy.

High intensity focused ultrasound (HIFU) has demonstrated its safety, efficacy and noninvasiveness in the ablation of solid tumor. However, its further application is limited by its inherent deficiencies, such as postoperative recurrence caused by incomplete ablation and excessive intensity affecting surrounding healthy tissues. Recent research has indicated that the integration of nanomaterials with HIFU exhibits a promising synergistic effect in tumor ablation. The concurrent utilization of nanomaterials with HIFU can help overcome the limitations of HIFU by improving targeting and ablation efficiency, expanding operation area, increasing operation accuracy, enhancing stability and bio-safety during the process. It also provides a platform for multi-therapy and multi-mode imaging guidance. The present review comprehensively expounds upon the synergistic mechanism between nanomaterials and HIFU, summarizes the research progress of nanomaterials as cavitation nuclei and drug carriers in combination with HIFU for tumor ablation. Furthermore, this review highlights the potential for further exploration in the development of novel nanomaterials that enhance the synergistic effect with HIFU on tumor ablation.

PDE12 disrupts mitochondrial oxidative phosphorylation and mediates mitochondrial dysfunction to induce oral mucosal epithelial barrier damage in oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic oral mucosal disease. The pathological changes of OSF include epithelial damage and subepithelial matrix fibrosis. This study aimed to reveal the epithelial injury mechanism of OSF. A histopathological method was used to analyze oral mucosal tissue from OSF patients and OSF rats. The expression of PDE12 in the oral epithelium was analyzed by immunohistochemistry. The epithelial-mesenchymal transition (EMT) and tight junction proteins in arecoline-treated HOKs were explored by western blotting. Epithelial leakage was assessed by transepithelial electrical resistance and lucifer yellow permeability. The expression of PDE12 and the mitochondrial morphology, mitochondrial permeability transition pore opening, mitochondrial membrane potential, and mitochondrial reactive oxygen species (mtROS) were evaluated in arecoline-induced HOKs. Oxidative phosphorylation (OXPHOS) complexes and ATP content were also explored in HOKs. The results showed significant overexpression of PDE12 in oral mucosal tissue from OSF patients and rats. PDE12 was also overexpressed and aggregated in mitochondria in arecoline-induced HOKs, resulting in dysfunction of OXPHOS and impaired mitochondrial function. An EMT, disruption of tight junctions with epithelial leakage, and extracellular matrix remodeling were also observed. PDE12 overexpression induced by PDE12 plasmid transfection enhanced the mtROS level and interfered with occludin protein localization in HOKs. Interestingly, knockdown of PDE12 clearly ameliorated arecoline-induced mitochondrial dysfunction and epithelial barrier dysfunction in HOKs. Therefore, we concluded that overexpression of PDE12 impaired mitochondrial OXPHOS and mitochondrial function and subsequently impaired epithelial barrier function, ultimately leading to OSF. We suggest that PDE12 may be a new potential target against OSF.

A Mixture of T-Cell Epitope Peptides Derived from Human Respiratory Syncytial Virus F Protein Conferred Protection in DR1-TCR Tg Mice.

Human respiratory syncytial virus (HRSV) poses a significant disease burden on global health. To date, two vaccines that primarily induce humoral immunity to prevent HRSV infection have been approved, whereas vaccines that primarily induce T-cell immunity have not yet been well-represented. To address this gap, 25 predicted T-cell epitope peptides derived from the HRSV fusion protein with high human leukocyte antigen (HLA) binding potential were synthesized, and their ability to be recognized by PBMC from previously infected HRSV cases was assessed using an ELISpot assay. Finally, nine T-cell epitope peptides were selected, each of which was recognized by at least 20% of different donors' PBMC as potential vaccine candidates to prevent HRSV infection. The protective efficacy of F-9PV, a combination of nine peptides along with CpG-ODN and aluminum phosphate (Al) adjuvants, was validated in both HLA-humanized mice (DR1-TCR transgenic mice, Tg mice) and wild-type (WT) mice. The results show that F-9PV significantly enhanced protection against viral challenge as evidenced by reductions in viral load and pathological lesions in mice lungs. In addition, F-9PV elicits robust Th1-biased response, thereby mitigating the potential safety risk of Th2-induced respiratory disease during HRSV infection. Compared to WT mice, the F-9PV mice exhibited superior protection and immunogenicity in Tg mice, underscoring the specificity for human HLA. Overall, our results demonstrate that T-cell epitope peptides provide protection against HRSV infection in animal models even in the absence of neutralizing antibodies, indicating the feasibility of developing an HRSV T-cell epitope peptide-based vaccine.

Well-defined in-textile photolithography towards permeable textile electronics.

Textile-based wearable electronics have attracted intensive research interest due to their excellent flexibility and breathability inherent in the unique three-dimensional porous structures. However, one of the challenges lies in achieving highly conductive patterns with high precision and robustness without sacrificing the wearing comfort. Herein, we developed a universal and robust in-textile photolithography strategy for precise and uniform metal patterning on porous textile architectures. The as-fabricated metal patterns realized a high precision of sub-100 µm with desirable mechanical stability, washability, and permeability. Moreover, such controllable coating permeated inside the textile scaffold contributes to the significant performance enhancement of miniaturized devices and electronics integration through both sides of the textiles. As a proof-of-concept, a fully integrated in-textiles system for multiplexed sweat sensing was demonstrated. The proposed method opens up new possibilities for constructing multifunctional textile-based flexible electronics with reliable performance and wearing comfort.

Macrophage barrier in the tumor microenvironment and potential clinical applications.

The tumor microenvironment (TME) constitutes a complex microenvironment comprising a diverse array of immune cells and stromal components. Within this intricate context, tumor-associated macrophages (TAMs) exhibit notable spatial heterogeneity. This heterogeneity contributes to various facets of tumor behavior, including immune response modulation, angiogenesis, tissue remodeling, and metastatic potential. This review summarizes the spatial distribution of macrophages in both the physiological environment and the TME. Moreover, this paper explores the intricate interactions between TAMs and diverse immune cell populations (T cells, dendritic cells, neutrophils, natural killer cells, and other immune cells) within the TME. These bidirectional exchanges form a complex network of immune interactions that influence tumor immune surveillance and evasion strategies. Investigating TAM heterogeneity and its intricate interactions with different immune cell populations offers potential avenues for therapeutic interventions. Additionally, this paper discusses therapeutic strategies targeting macrophages, aiming to uncover novel approaches for immunotherapy. Video Abstract.

A monolithically integrated in-textile wristband for wireless epidermal biosensing.

Textile bioelectronics that allow comfortable epidermal contact hold great promise in noninvasive biosensing. However, their applications are limited mainly because of the large intrinsic electrical resistance and low compatibility for electronics integration. We report an integrated wristband that consists of multifunctional modules in a single piece of textile to realize wireless epidermal biosensing. The in-textile metallic patterning and reliable interconnect encapsulation contribute to the excellent electrical conductivity, mechanical robustness, and waterproofness that are competitive with conventional flexible devices. Moreover, the well-maintained porous textile architectures deliver air permeability of 79 mm s-1 and moisture permeability of 270 g m-2 day-1, which are more than one order of magnitude higher than medical tapes, thus ensuring superior wearing comfort. The integrated in-textile wristband performed continuous sweat potassium monitoring in the range of 0.3 to 40 mM with long-term stability, demonstrating its great potential for wearable fitness monitoring and point-of-care testing.

Influence of ligand variation on the deactivation process of metal-to-ligand charge transfer excited states in quadruply bonded dimolybdenum complexes.

To explore the dynamics of metal-to-ligand charge transfer (MLCT) excited states involving covalently bonded dimetal units, a series of quadruply bonded dimolybdenum (Mo2) complexes, namely, [Mo2]-ph, [Mo2]-naph, and [Mo2]-anth, were synthesized and characterized. Our investigations reveal a non-radiative process associated with the deactivation of the MLCT state into a low-lying dimetal-centered triplet state (3Mo2-δδ*), resulting in the populated MLCT states in these molecular systems exhibiting either extremely weak emission or being non-emissive. The influence of ligand variation on the dynamics of MLCT states was examined using femtosecond transient absorption spectroscopy, with deactivation time constants determined to be 1.9 ps for [Mo2]-ph, 6.5 ps for [Mo2]-naph, and 49 ps for [Mo2]-anth. This electron transfer behaviour follows an inverse energy-gap law, contrary to the general guideline that applies to the decay of the MLCT state back to the electronic ground state. This result offers valuable insights into understanding the photochemical and photophysical properties of covalently bonded dimetal complexes.

Occurrence and influencing factors of cyclosporine A on the kidney injury following allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis.

OBJECTIVE: Whether cyclosporine A (CsA) is a risk factor of kidney injury after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has not been determined. We aim to comprehensively review the correlation and influencing factors between CsA and kidney injury in patients following allo-HSCT. METHODS: We searched PubMed, Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, VIP, Wanfang and CBM Database from inception to March 2022. Two researchers independently conducted literature screening, data extraction and quality assessment. Qualitative and quantitative methods were combined to analyze the data. RESULTS: We included a total of 30 studies. Meta-analyses of total incidence of kidney injury related to CsA was 37.0% [95% CI (25.4%, 48.6%); n = 15]. The proportion of CsA-related acute kidney injury to total acute kidney injury following allo-HSCT was 59.7% [95% CI (49.1%, 70.3%); n = 9]. One study found that AKI had a significant association with CsA in multivariate analysis [RR = 6.173; 95% CI (4.032, 9.434)]. With respect to cyclosporine combination and nephrotoxicity, 6/9 studies demonstrated that the concomitant medications for CsA (especially aminoglycoside antibiotics and amphotericin B) had negative effect on kidney functions related to CsA in allo-HSCT patients. No consensus was reached for "dose of CsA", "duration of CsA use", "comorbidities" and "CsA levels" across studies. CONCLUSIONS: CsA may be a risk factor for kidney injury in patients following allo-HSCT, especially the concomitant use of CsA and nephrotoxic medications.

Cognitive Aging: How the Brain Ages?

Cognitive aging refers to the cognitive changes or functional decline that comes with age. The relation between aging and functional declines involves various aspects of cognition, including memory, attention, processing speed, and executive function. In this chapter, we have introduced several dimensions about cognitive aging trajectories. Meanwhile, we have reviewed the history of the study of cognitive aging and expatiated two trends that are particularly noteworthy in the effort to elucidate the process of aging. One is that the differences between components of mental abilities have become gradually specified. The other one is a growing interest in the neural process, which relates changes in the brain structure to age-related changes in cognition. Lastly, as the basis of cognitive function, brain structures and functions change during aging, and these changes are reflected in a corresponding decline in cognitive function. We have discussed the patterns of reorganization of various structural and functional aging processes of the brain and their relationship with cognitive function.

Global, regional and national availability of essential medicines for children, 2009-2020: a systematic review and meta-analysis.

BACKGROUND: Access to essential medicines is a vital component of universal health coverage. The low availability of essential medicines for children (EMC) has led the World Health Organization (WHO) to issue a number of resolutions calling on member states on its improvement. But its global progress has been unclear. We aimed to systematically evaluate the progress of availability of EMC over the past decade across economic regions and countries. METHODS: We searched eight databases from inception to December 2021 and reference lists to identify included studies. Two reviewers independently conducted literature screening, data extraction and quality evaluation. This study was registered with PROSPERO, CRD42022314003. RESULTS: Overall, 22 cross-sectional studies covering 17 countries, 4 income groups were included. Globally, the average availability rates of EMC were 39.0% (95%CI: 35.5-42.5%) in 2009-2015 and 43.1% (95%CI: 40.1-46.2%) in 2016-2020. Based on the World Bank classification of economic regions, income was not proportional to availability. Nationally, the availability rate of EMC was reasonable and high (> 50%) in only 4 countries, and low or very low for the rest 13 countries. The availability rates of EMC in primary healthcare centers had increased, while that for other levels of hospitals slightly declined. The availability of original medicines decreased while that of generic medicines was stable. All drug categories had not achieved the high availability rate. CONCLUSION: The availability rate of EMC was low globally, with slight increase in the last decade. Continuous monitoring and timely reporting of the availability of EMC are also needed to facilitate targets setting and inform relevant policy making.

Megacity's pathway toward sustainable food waste management and its environmental performance in a developing country: Evidence from Shanghai, China.

Due to the far distance impact on resident, aquatic and soil ecosystem health, food waste disposal becomes the focus of municipal waste strategy in developing countries. Shanghai is a leading city in China, its evolution of food waste management can indicate the coming future of the nation. In this city, from 1986 to 2020, the open dumping, landfill and incineration of food waste had been gradually banned, replaced by centralized compost and anaerobic digestion and other recovery ways. This study selected ten scenarios, ever used for food/mixed waste disposal in Shanghai, and analyzed the environmental impact change during the period 1986-2020. Life cycle assessment showed that although the generation of food waste raised rapidly, the total environmental impact, which was dominated by Freshwater Aquatic Ecotoxicity Potential, displayed a sharp decrease as 96.09 %, and Global Warming Potential decreased by 28.14 %. Substantial efforts should be made to improve the collection rate of biogas and landfill gas to reduce environmental impact, and quality of residues from anaerobic digestion and compost plants should be improved and utilized in its legal ways. Driving forces for the goal of sustainable food waste management in Shanghai involved economic development, environmental regulations and the supporting national/local standards.

Prevalence, risk factors, impact and management of pneumonia among preschool children in Chinese seven cities: a cross-sectional study with interrupted time series analysis.

BACKGROUND: Pneumonia is a common disease worldwide in preschool children. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of pneumonia among preschool children. We therefore investigated the prevalence of pneumonia among preschool children in Chinese seven representative cities, and explore the possible risk factors of pneumonia on children, with a view to calling the world's attention to childhood pneumonia to reduce the prevalence of childhood pneumonia. METHODS: Two group samples of 63,663 and 52,812 preschool children were recruited from 2011 and 2019 surveys, respectively. Which were derived from the cross-sectional China, Children, Homes, Health (CCHH) study using a multi-stage stratified sampling method. This survey was conducted in kindergartens in seven representative cities. Exclusion criteria were younger than 2 years old or older than 8 years old, non-permanent population, basic information such as gender, date of birth and breast feeding is incomplete. Pneumonia was determined on the basis of parents reported history of clearly diagnosed by the physician. All participants were assessed with a standard questionnaire. Risk factors for pneumonia, and association between pneumonia and other respiratory diseases were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was evaluated by the parents' reported history of physician diagnosis, longitudinal comparison of risk factors in 2011 and 2019. RESULTS: In 2011 and 2019, 31,277 (16,152 boys and 15,125 girls) and 32,016 (16,621 boys and 15,395 girls) preschool children aged at 2-8 of permanent population completed the questionnaire, respectively, and were thus included in the final analysis. The findings showed that the age-adjusted prevalence of pneumonia in children was 32.7% in 2011 and 26.4% in 2019. In 2011, girls (odds ratio [OR] 0.91, 95%CI [confidence interval]0.87-0.96; p = 0.0002), rural (0.85, 0.73-0.99; p = 0.0387), duration of breastfeeding ≥ 6 months(0.83, 0.79-0.88; p < 0.0001), birth weight (g) ≥ 4000 (0.88, 0.80-0.97; p = 0.0125), frequency of putting bedding to sunshine (Often) (0.82, 0.71-0.94; p = 0.0049), cooking fuel type (electricity) (0.87, 0.80-0.94; p = 0.0005), indoor use air-conditioning (0.85, 0.80-0.90; p < 0.0001) were associated with a reduced risk of childhood pneumonia. Age (4-6) (1.11, 1.03-1.20; p = 0.0052), parental smoking (one) (1.12, 1.07-1.18; p < 0.0001), used antibiotics (2.71, 2.52-2.90; p < 0.0001), history of parental allergy (one and two) (1.21, 1.12-1.32; p < 0.0001 and 1.33, 1.04-1.69; p = 0.0203), indoor dampness (1.24, 1.15-1.33; p < 0.0001), home interior decoration (1.11, 1.04-1.19; p = 0.0013), Wall painting materials (Paint) (1.16, 1.04-1.29; p = 0.0084), flooring materials (Laminate / Composite wood) (1.08, 1.02-1.16; p = 0.0126), indoor heating mode(Central heating)(1.18, 1.07-1.30, p = 0.0090), asthma (2.38, 2.17-2.61; p < 0.0001), allergic rhinitis (1.36, 1.25-1.47; p < 0.0001), wheezing (1.64, 1.55-1.74; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (2.53, 2.31-2.78; p < 0.0001), allergic rhinitis (1.41, 1.29-1.53; p < 0.0001) and wheezing (1.64, 1.55-1.74; p < 0.0001). In 2019, girls (0.92, 0.87-0.97; p = 0.0019), duration of breastfeeding ≥ 6 months (0.92, 0.87-0.97; p = 0.0031), used antibiotics (0.22, 0.21-0.24; p < 0.0001), cooking fuel type (Other) (0.40, 0.23-0.63; p = 0.0003), indoor use air-conditioning (0.89, 0.83-0.95; p = 0.0009) were associated with a reduced risk of childhood pneumonia. Urbanisation (Suburb) (1.10, 1.02-1.18; p = 0.0093), premature birth (1.29, 1.08-1.55; p = 0.0051), birth weight (g) < 2500 (1.17, 1.02-1.35; p = 0.0284), parental smoking (1.30, 1.23-1.38; p < 0.0001), history of parental asthma (One) (1.23, 1.03-1.46; p = 0.0202), history of parental allergy (one and two) (1.20, 1.13-1.27; p < 0.0001 and 1.22, 1.08-1.37; p = 0.0014), cooking fuel type (Coal) (1.58, 1.02-2.52; p = 0.0356), indoor dampness (1.16, 1.08-1.24; p < 0.0001), asthma (1.88, 1.64-2.15; p < 0.0001), allergic rhinitis (1.57, 1.45-1.69; p < 0.0001), wheezing (2.43, 2.20-2.68; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (1.96, 1.72-2.25; p < 0.0001), allergic rhinitis (1.60, 1.48-1.73; p < 0.0001) and wheezing (2.49, 2.25-2.75; p < 0.0001). CONCLUSIONS: Pneumonia is prevalent among preschool children in China, and it affects other childhood respiratory diseases. Although the prevalence of pneumonia in Chinese children shows a decreasing trend in 2019 compared to 2011, a well-established management system is still needed to further reduce the prevalence of pneumonia and reduce the burden of disease in children.

Global trends in semen quality of young men: a systematic review and regression analysis.

PURPOSE: Many studies have reported declines in semen quality mainly focused on total sperm counts (TSC) and sperm concentration (SC), ignoring the importance of progressive motile sperm (PR), total motile sperm (TM), and normal morphological sperm (NM). Therefore, we performed a comprehensive meta-analysis to explore the trend in semen quality of young men. METHODS: We searched 3 English databases and 4 Chinese databases from January 1980 to August 2022. Random-effect meta-analyses and weighted linear regression models were conducted to perform the trend in semen quality. RESULTS: Finally, 162 eligible studies including 264,665 men from 28 countries were got between 1978 and 2021. Significant decreases were observed in TSC (- 3.06 million/year, 95% CI - 3.28 to - 2.84), SC (- 0.47 million/ml/year, 95% CI - 0.51 to - 0.43), and PR (- 0.15%/year, 95% CI - 0.20 to - 0.09), and there was an upward trend in TM (0.28%/year, 95% CI 0.24 to 0.32). The results of meta-regression analyses indicated that age, continent, income, WHO criteria, and abstinence time significantly impacted on TSC, SC, PR, and TM. Positive regression coefficients were observed in some categories suggesting that outcomes might not be declining and even increasing in these subgroups. CONCLUSIONS: Downward trends in semen quality among global young men were observed in our study, including TSC, SC, and PR. But TM did not appear to be trending down or even to be leveling off. More studies are needed to focus on the causes of the declines.

Antibacterial Mesoporous Silica Granules Containing a Stable N-Halamine Moiety.

High-efficacy and regenerable antimicrobial silica granules were prepared via oxa-Michael addition between poly(vinyl alcohol) (PVA) and methylene-bis-acrylamide (MBA) under the catalysis of sodium carbonate in an aqueous solution. Diluted water glass was added, and the solution pH was adjusted to about 7 to precipitate PVA-MBA modified mesoporous silica (PVA-MBA@SiO2) granules. N-Halamine-grafted silica (PVA-MBA-Cl@SiO2) granules were achieved by adding diluted sodium hypochlorite solution. It was found that a BET surface area of about 380 m2 g-1 for PVA-MBA@SiO2 granules and a Cl+% of about 3.80% for PVA-MBA-Cl@SiO2 granules could be achieved under optimized preparation conditions. Antimicrobial tests showed that the as-prepared antimicrobial silica granules were capable of about a 6-log inactivation of Staphylococcus aureus and Escherichia coli O157:H7 within 10 min of contact. Furthermore, the as-prepared antimicrobial silica granules can be recycled many times due to the excellent regenerability of their N-halamine functional groups and can be saved for a long time. With the above-mentioned advantages, the granules have potential applications in water disinfection.

Availability of essential medicines, progress and regional distribution in China: a systematic review and meta-analysis.

Background: Essential medicines are the backbone of healthcare and meet the priority healthcare needs of the population. However, approximately one-third of the global population does not have access to essential medicines. Although China formulated essential medicine policies in 2009, the progress of availability of essential medicines and regional variations remains unknown. Therefore, this study was conducted to evaluate the availability of essential medicines, their progress, and regional distribution in China in the last decade. Methods: We searched eight databases from their inception to February 2022, relevant websites, and reference lists of included studies. Two reviewers selected studies, extracted data, and evaluated the risk of bias independently. Meta-analyses were performed to quantify the availability of essential medicines, their progress, and regional distribution. Results: Overall 36 cross-sectional studies conducted from 2009 to 2019 were included, with regional data for 14 provinces. The availability of essential medicines in 2015-2019 [28.1%, 95% confidence interval (CI): 26.4-29.9%] was similar to that in 2009-2014 (29.4%, 95% CI: 27.5-31.3%); lower in the Western region (19.8%, 95% CI: 18.1-21.5%) than Eastern (33.8%, 95% CI: 31.6-36.1%) and Central region (34.5%, 95% CI: 30.6-38.5%); very low for 8 Anatomical Therapeutic Chemical (ATC) categories (57.1%), and low for 5 categories (35.7%) among all ATC groups. Conclusion: The availability of essential medicines in China is low compared with the World Health Organization goal, has not changed much in the last decade, is unequal across regions, and lacks data for half of provinces. For policy-making, the monitoring system of the availability of essential medicines is to be strengthened to enable long-term surveillance, especially in provinces where the data has been missing. Meanwhile, Joint efforts from all stakeholders are warranted to improve the availability of essential medicines in China toward the universal health coverage target. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=315267, identifier: PROSPERO CRD42022315267.

Electronic coupling and electron transfer in hydrogen-bonded mixed-valence compounds.

Electron transfer provided by hydrogen bonds represents a unique and highly significant area of research, as it has a crucial role to play in a wide variety of chemical and biological systems. The hydrogen-bonded mixed-valence system, in the form of donor-hydrogen bond-acceptor, provides an ideal platform for exploring thermally-induced electron transfer across this non-covalent unit. Over the past decades, ongoing progress has been made in this field. Here we critically assess some studies on the qualitative and quantitative evaluation of electronic coupling and thermal electron transfer across hydrogen bond interface. Additionally, selected experimental examples are discussed in terms of intervalence charge transfer, with particular attention paid to the proton-coupled and often overlooked proton-uncoupled electron transfer pathway in hydrogen-bonded mixed-valence systems. We further highlight the major limitations of this research area and suggest potential directions for future exploration.

The price and affordability of essential medicines, progress and regional distribution in China: a systematic review.

Background: Essential medicine is a vital component to assure universal access to quality healthcare. However, the trend of affordability to essential medicines in China and its regional differences were not yet fully understood. This study aimed to systematically evaluate the price and affordability of essential medicines, their progress, and regional distribution in China in the last decades. Methods: We searched seven databases and three websites for potentially eligible studies from inception until March 2022. Studies on the price and affordability of essential medicines investigated in China were included. Median and interquartile range (IQR) was used to describe the price and affordability of essential medicines, and compared in three periods, before 2009, from 2009 to 2014, and from 2015 to 2019. Subgroup analysis was performed to examine the price and affordability by regions, health facilities, and ATC categories of medicines. The study was registered with PROSPERO (CRD42022310173). Results: A total of 65 studies including 11,639 health facilities investigated between 2006 and 2019 were included in this review. Median price ratios (MPR) and affordability of essential medicines were reported in 44 studies and 50 studies, respectively. The median MPRs of essential medicines in China was 1.59 (IQR: 5.39), with a tendency to rise first and then fall from 2006 to 2019. And the median affordability was equal to 0.88 (IQR: 2.58) days' wage of the lowest paid unskilled government worker, but steadily rose from 2006 to 2019. Subgroup analysis showed that the affordability in the western region (1.40, IQR: 2.88), urban area (0.95, IQR: 2.80), private sector (0.90, IQR: 2.30), of originator brands (OB) (2.90, IQR: 6.68), and antineoplastic and immunomodulating agents (5.68, IQR: 56.47) were worse than their counterparts. Conclusion: The prices of essential medicine were higher than international level, the overall affordability of essential medicines in China is acceptable but poor in the western region, for OB drugs and anti-cancer medicines. Further national essential medicine policies are needed to reduce regional disparities and improve the affordability of expensive drugs. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.