Efficient Lead Removal by Assembly of Bio-Derived Ellagate Framework, Which Enables Electrocatalytic Reduction of CO2 to Formate.

Lead (Pb) poisoning and CO2-induced global warming represent two exemplary environmental and energy issues threatening humanity. Various biomass-derived materials are reported to take up Pb and convert CO2 electrochemically into low-valent carbon species, but these works address the problems separately rather than settle the issues simultaneously. In this work, cheap, natural ellagic acid (EA) extracted from common plants is adopted to assemble a stable metal-organic framework (MOF), EA-Pb, by effective capture of Pb2+ ions in an aqueous medium (removal rate close to 99%). EA-Pb represents the first structurally well-defined Pb-based MOF showing selective electrocatalytic CO2-to-HCOO- conversion with Faradaic efficiency (FE) of 95.37% at -1.08 V versus RHE. The catalytic mechanism is studied by 13CO2 labeling, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and theoretical calculation. The use of EA-Pb as an electrocatalyst for CO2 reduction represents a 2-in-1 solution of converting detrimental wastes (Pb2+) as well as natural resources (EA) into wealth (electrocatalytic EA-Pb) for addressing the global warming issue.

Ni(II)-Pyrazolate Framework Bearing a Metalated Schiff-Base Moiety for Electrocatalytic Hydrogen Evolution.

A robust and porous Ni-based metal-organic framework (MOF), NiL1, was assembled from Ni(II) ions and a dipyrazolate linker (L12-). A Ni(II)-anchored MOF catalyst Ni@NiL1-Sal has been successfully prepared by post-synthetic modification (PSM) condensation between NiL1 with salicylaldehyde, followed by chelation of Ni(II) ions by salicylaldimine as a secondary active site. Ni@NiL1-Sal with carbon black was found to exhibit enhanced electrocatalytic hydrogen evolution reaction (HER) performance (the smallest overpotential, 384 mV, and Tafel slope, 87 mV dec-1) when compared with primitive NiL1 and NiL1-Sal. Such improvement in HER highlights the creation of unambiguous secondary active sites as an avenue to the rational design of a functional MOF-based electrocatalyst.

DFT Study on the Oxidation Mechanism of Common Cyclic Carbonates in the Presence of BF4- Anions.

Oxidative decomposition reactions of common cyclic carbonates in the presence of BF4- anions were investigated using density functional theory. A polarized continuum model was utilized to model solvent effects in the oxidation of ethylene carbonate (EC) and propylene carbonate (PC) clusters. We have found that the presence of BF4- significantly reduces EC and PC oxidation stability, from 7.11 to 6.17 and from 7.10 to 6.06 V (vs Li+/Li), respectively. The sequence of EC and PC oxidative decomposition paths and the oxidative products were affected by the BF4- anion. The decomposition products of the oxidized EC-BF4- contained CO2, vinyl alcohol, and acetaldehyde, while the decomposition products of the oxidized PC-BF4- contained CO2, acetone, and propanal, in agreement with the previous experimental studies. The oxidative decomposition reactions for PC-BF4- are compared with those for the isolated PC, PC2, PC-ClO4-, and PC-PF6-.

Celastrol attenuates hepatitis C virus translation and inflammatory response in mice by suppressing heat shock protein 90ß.

Hepatitis C virus (HCV) infection is one of the major factors to trigger a sustained hepatic inflammatory response and hence hepatocellular carcinoma (HCC), but direct-acting-antiviral (DAAs) was not efficient to suppress HCC development. Heat shock protein 90 kDa (HSP90) is highly abundant in different types of cancers, and especially controls protein translation, endoplasmic reticulum stress, and viral replication. In this study we investigated the correlation between the expression levels of HSP90 isoforms and inflammatory response marker NLRP3 in different types of HCC patients as well as the effect of a natural product celastrol in suppression of HCV translation and associated inflammatory response in vivo. We identified that the expression level of HSP90ß isoform was correlated with that of NLRP3 in the liver tissues of HCV positive HCC patients (R2 = 0.3867, P < 0.0101), but not in hepatitis B virus-associated HCC or cirrhosis patients. We demonstrated that celastrol (3, 10, 30 µM) dose-dependently suppressed the ATPase activity of both HSP90α and HSP90ß, while its anti-HCV activity was dependent on the Ala47 residue in the ATPase pocket of HSP90ß. Celastrol (200 nM) halted HCV internal ribosomal entry site (IRES)-mediated translation at the initial step by disrupting the association between HSP90ß and 4EBP1. The inhibitory activity of celastrol on HCV RNA-dependent RNA polymerase (RdRp)-triggered inflammatory response also depended on the Ala47 residue of HSP90ß. Intravenous injection of adenovirus expressing HCV NS5B (pAde-NS5B) in mice induced severe hepatic inflammatory response characterized by significantly increased infiltration of immune cells and hepatic expression level of Nlrp3, which was dose-dependently ameliorated by pretreatment with celastrol (0.2, 0.5 mg/kg, i.p.). This study reveals a fundamental role of HSP90ß in governing HCV IRES-mediated translation as well as hepatic inflammation, and celastrol as a novel inhibitor of HCV translation and associated inflammation by specifically targeting HSP90ß, which could be developed as a lead for the treatment of HSP90ß positive HCV-associated HCC.

High-Quality Genome Resource of Bacillus subtilis N4, a Biological Control Agent Isolated from Phoebe bournei.

Bacillus subtilis strain N4, an endophyte isolated from the healthy leaves of Phoebe bournei, possesses an excellent biocontrol effect against stem canker of P. bournei caused by Lasiodiplodia theobromae. To understand its biocontrol mechanism, we assembled a high-quality genome of N4 using a combination of second- and third-generation sequencing methods. The N4 genome contained one circular DNA chromosome of 4,218,183 bp length with 43.5% GC content and 11 secondary metabolite biosynthesis gene clusters, including genes for subtilomycin synthesis. This high-quality genome assembly and gene annotation resource will provide better insights into the biocontrol potential of B. subtilis strain N4 against stem canker of P. bournei.

Hepatocyte Nuclear Factor 4α Prevents the Steatosis-to-NASH Progression by Regulating p53 and Bile Acid Signaling (in mice).

BACKGROUND AND AIMS: Hepatocyte nuclear factor 4α (HNF4α) is highly enriched in the liver, but its role in the progression of nonalcoholic liver steatosis (NAFL) to NASH has not been elucidated. In this study, we investigated the effect of gain or loss of HNF4α function on the development and progression of NAFLD in mice. APPROACH AND RESULTS: Overexpression of human HNF4α protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of Hnf4α had opposite effects. HNF4α prevented hepatic triglyceride accumulation by promoting hepatic triglyceride lipolysis, fatty acid oxidation, and VLDL secretion. Furthermore, HNF4α suppressed the progression of NAFL to NASH. Overexpression of human HNF4α inhibited HFCF diet-induced steatohepatitis in control mice but not in hepatocyte-specific p53-/- mice. In HFCF diet-fed mice lacking hepatic Hnf4α, recapitulation of hepatic expression of HNF4α targets cholesterol 7α-hydroxylase and sterol 12α-hydroxylase and normalized hepatic triglyceride levels and attenuated steatohepatitis. CONCLUSIONS: The current study indicates that HNF4α protects against diet-induced development and progression of NAFLD by coordinating the regulation of lipolytic, p53, and bile acid signaling pathways. Targeting hepatic HNF4α may be useful for treatment of NASH.

Microenvironment Regulation of Metal-Organic Frameworks to Anchor Transition Metal Ions for the Electrocatalytic Hydrogen Evolution Reaction.

Bearing triazine-centered linkers, three primitive metal-organic frameworks (MOFs) with a Zr6O4 cluster have been prepared as ZrL1 (without any branch), ZrL2 (with -F), and ZrL3 (with -SCH3). The electrocatalytic hydrogen evolution reaction (HER) by their pristine and transition metal-loaded (TM-loaded) forms was studied. It was found that the loading of TM ions could enhance the electrocatalytic power of these TM-loaded MOFs in HER, as reflected by their lower overpotentials and smaller Tafel slopes when compared with primitive MOFs. More importantly, the best electrocatalytic HER performance of ZrL3-TM among all TM-loaded MOFs studied in this work highlights the effective housing of TM ions for unambiguous active sites through cooperative coordination by triazinic N and thioether pendants. This work proposes microenvironment regulation of MOFs as an effective strategy to enhance the electrocatalytic activity of MOF materials.

Analysis of child mortality under 5 years old in Liuyang City from 2013 to 2020. / 浏阳市2013至2020年5岁以下儿童死亡状况分析.

OBJECTIVES: To provide reference basis for reducing the mortality for children under 5 years old and promote the healthy development, the mortality for children under 5 years old and the main causes for death in Liuyang City from 2013 to 2020 are analyzed. METHODS: The data of 725 cases of death for children under 5 years old in Liuyang City from 2013 to 2020 were collected.The causes and difference of death among the children were analyzed retrospectively by descriptive statistic methods. RESULTS: There were a total of 144 516 live births in Liuyang City from 2013 to 2020. The mortality for children under 5 years old was 5.01‰, for infants was 3.39‰, and for newborns was 1.63‰. The male child mortality was 5.28‰, and the female child mortality rate was 4.72‰, with significant difference (P>0.05). The mortality for children under 5 years old was seasonal fluctuation, without significant difference among seasons (P>0.05). For the past 5 years, the top 3 causes for death among children under 5 years old were preterm birth and low birth weight, congenital heart disease, and pneumonia. Before death, 341 cases (47.04%) were treated in provincial hospitals, 198 cases (27.31%) in county-level hospitals, 56 cases (7.72%) in village-level hospitals, and 130 cases (17.93%) were not treated. CONCLUSIONS: The mortality for children under 5 years old in Liuyang City is gradually reduced in the past 5 years. The main causes for death are premature birth and low birth weight, congenital heart disease and pneumonia. We should develop healthy education, improve the rate of prenatal diagnosis, promote the construction of obstetrics and paediatrics, and fundamentally reduce the mortality for children under 5 years old.

Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide.

Andrographis paniculata (A. paniculata) is a medicinal plant traditionally used as anti-inflammation and anti-bacteria herb. Andrographolide, the major active component of A. paniculata, exhibits diverse pharmacological activities, including anti-inflammation, anti-cancer, anti-obesity, anti-diabetes, and other activities. In this article, we comprehensively review the therapeutic potential of A. paniculata and andrographolide focusing on the mechanisms of action and clinical application. We systemically discuss the structure-activity relationship of andrographolide and derivatives. Despite the various pharmacological activities and formula of A. paniculata and andrographolide, we propose further development of more structural derivatives of andrographolide with reduced toxicity and increased therapeutic efficacy is still needed for the clinical application of this ancient mighty herb and its major component.

Structure-activity relationships of cryptopleurine analogs with E-ring modifications as anti-hepatitis C virus agents.

The tylophorine analog rac-cryptopleurine exhibited potent anti-hepatitis C virus (HCV) activity through allosteric regulation of ATPase activity of heat shock cognate protein 70 (Hsc70). We evaluated the impact of modifications on the E-ring of rac-cryptopleurine to the inhibitory activity against HCV replication and regulation of ATPase activity of Hsc70. Cryptopleurine analog YXM-110 with a 13α-hydroxyl group maintained activity against HCV and promoted ATP/ADP turnover of Hsc70; however, compounds with hydroxyl groups at other positions or with other orientations (YXM-109, YXM-139, and YXM-140) did not exhibit similar activities. Size modification or heteroatom incorporation of the E-ring led to loss of anti-HCV activity. Promotion of the chaperone activity of Hsc70 with carboxyl terminus Hsc70 interacting protein (CHIP) further enhanced the anti-HCV activity of rac-cryptopleurine and XYM-110. This structure-activity relationship (SAR) study refined structural design and optimization for developing rac-crytopleurine analogs as potent anti-HCV agents targeted against the host factor involved in HCV replication.

Andrographolide derivative as STAT3 inhibitor that protects acute liver damage in mice.

Sustained activation of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway contributed to the progression of cancer and liver diseases. STAT3 signaling inhibitor has been extensively investigated for pharmacological use. We synthesized a series of andrographolide derivatives, and characterized their activity against STAT3 signaling pathway both in vitro and in the CCl4-induced acute liver damage mice model. Among these derivatives, compound 24 effectively inhibited phosphorylation and dimerization of STAT3 but not its DNA binding activity. Compound 24 significantly ameliorated carbon tetrachloride-induced acute liver damage in vivo without changing mice body weight. Treatment with 24 attenuated hepatic pathologic damage and promoted hepatic proliferation and activation of STAT3. Compound 24 inhibited elevated expression of α-smooth muscle actin and serum pro-inflammatory cytokines downstream of STAT3 but not those factors that are regulated by NF-κB or SMADs. In summary, our results suggest that compound 24 may serve as a potential therapeutic agent for the treatment of hepatic damage or a liver protection agent via regulating STAT3 activation.

C21-steroidal pregnane sapogenins and their derivatives as anti-inflammatory agents.

During the screening of natural anti-inflammatory agent, we identified some C21-steroidal pregnane sapogenins or the derivatives to inhibit TLR2, TLR3, and TLR4-initiatedinflammatory responses respectively. Treatment with active compounds 10, 2j and 3p failed to impact tumor necrosis factor-α (TNF-α) induced nucleus translocation of NF-κB p65 subunit. However, these compounds regulated distinct canonical or non-canonical NF-κB family members. Ectopic expression of TNF receptor associated factor 6 (TRAF6) abrogated the inhibitory activity of the compounds on production of pro-inflammatory cytokines downstream of TLR4. These results suggested that compounds 10, 2j, and 3p suppressed TLR-initiated innate immunity through TRAF6 with differential regulation of NF-κB family proteins.

Herbal Medicine Offered as an Initiative Therapeutic Option for the Management of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant cancer and is the third leading cause of death worldwide. Effective treatment of this disease is limited by the complicated molecular mechanism underlying HCC pathogenesis. Thus, therapeutic options for HCC management are urgently needed. Targeting the Wnt/ß-catenin, Hedgehog, Notch, and Hippo-YAP signaling pathways in cancer stem cell development has been extensively investigated as an alternative treatment. Herbal medicine has emerged as an initiative therapeutic option for HCC management because of its multi-level, multi-target, and coordinated intervention effects. In this article, we summarized the recent progress and clinical benefits of targeting the above mentioned signaling pathways and using natural products such as herbal medicine formulas to treat HCC. Proving the clinical success of herbal medicine is expected to deepen the knowledge on herbal medicine efficiency and hasten the adoption of new therapies. Copyright © 2016 John Wiley & Sons, Ltd.

In Vitro Study on Anti-Hepatitis C Virus Activity of Spatholobus suberectus Dunn.

Hepatitis C virus (HCV) infects 200 million people worldwide, and 75% of HCV cases progress into chronic infections, which consequently cause cirrhosis and hepatocellular carcinoma. HCV infection is treated with currently considered standard drugs, including direct anti-viral agents (DAAs), alone or in combination with peginterferon-α plus ribavirin. However, sustained viral responses vary in different cohorts, and high costs limit the broad use of DAAs. In this study, the ethanol and water extracts of 12 herbs from Lingnan in China were examined in terms of their inhibitory effect on HCV replication. Among the examined extracts, Spatholobus suberectus ethanol extracts suppressed HCV replication. By comparison, Extracts from Fructus lycii, Radix astragali (root), Rubus chingii Hu (fruit), Flos chrysanthemi Indici (flower), Cassia obtusifolia (seed), Lonicera japonica Thunb (flower), Forsythia suspense Thunb (fruit), Poria cocos (sclerotia), Carthamus tinctorius L. (flower), Crataegus pinnatifida Bge. (fruit), and Leonurus japonicas Houtt. (leaf) extracts failed to show a similar activity. Active S. suberectus fractions containing tannins as the major component also inhibited the in vitro translation of HCV RNA. The combination treatments of single compounds, such as epigallocatechin gallate and epicatechin gallate, were not as potent as crude S. suberectus fractions; therefore, crude S. suberectus extract may be a potential alternative treatment against HCV either alone or in combination with other agents.

Prevalence, trend, and inequality of prolonged exclusive breastfeeding among children aged 6-23 months old in India from 1992-2021: A cross-sectional study of nationally representative, individual-level data.

Background: Prolonged exclusive breastfeeding (PEB) for children older than six months old is a threat to appropriate complementary feeding practices. This study aims to examine the trend of PEB among children aged 6-23 months in India. Methods: We adopted five waves of National Family Health Survey (NFHS) data between 1992-93 and 2019-21. PEB was defined as children aged six months and above currently consuming breastmilk as the only source of energy, protein and micronutrients. We generated descriptive statistics and a series of multivariable logistic regressions to estimate the prevalence and trend in the PEB rate. Moreover, we assessed how child age and socioeconomic factors (i.e. child gender and age, place of residence, household wealth, and maternal education) were related with PEB using mutually and single-adjusted model. Results: There were 184 891 Indian children aged 6-23 months old included in this study with 48.0% being female. We found that the proportion of PEB increased from 4.3% in 1992 to 7.7% in 2021, of which the rate for children aged six-eight months rose from 14.0 to 20.1%. Our results showed that children who were from poorer households or with lower-educated mothers were more likely to experience prolonged exclusive breastfed. Take the year of 2019-21 as an example, compared to the households of the richest quintile, children from households of the poorer quintile were significantly more likely to experience PEB, with odds ratio (OR) of 1.33 (95% confidence interval (CI) = 1.09-1.61). Moreover, children with illiterate mothers had 21% higher odds of having prolonged exclusively breastfeeding (OR = 1.21; 95% CI = 1.01-1.44) compared with children with mothers who have college and above education. Conclusions: PEB among children over six months old is prevalent in India, particularly among children from disadvantaged households. Poverty reduction and maternal education are of great potential importance for policymakers to promote appropriate complementary feeding practice.

Association between concurrence of multiple risk factors and under-5 mortality: a pooled analysis of data from Demographic and Health Survey in 61 low-and-middle-income countries.

Background: Exposure to multiple risk factors is prevalent in low-and middle-income countries (LMICs), challenging one-directional strategies to address preventable under-5 mortality (U5M). This study aims to assess the associations between concurrence of multiple risk factors and U5M in LMICs. Methods: We extracted data from the Demographic and Health Surveys conducted between 2010 and 2021 across 61 LMICs. Our primary outcome was U5M, defined as deaths from birth to 59 months. Binary logistic regression model was applied to ascertain the association between U5M and a total of 20 critical risk factors. Upon identifying the risk factors demonstrating the strongest associations, we investigated the simultaneous presence of multiple risk factors in each individual and assessed their combined effects on U5M with logistic regression models. Findings: Of the 604,372 under-5 children, 18,166 (3.0%) died at the time of the survey. Unsatisfied family planning needs was the strongest risk factor for U5M (odds ratio [OR]: 2.0, 95% confidence interval [CI]: 1.9-2.1), followed by short birth interval (<18 months; OR: 2.0, 95% CI: 1.9-2.1), small birth size (OR: 2.0, 95% CI: 1.8-2.1), never breastfed or delayed breastfeeding (OR: 2.0, 95% CI: 1.9-2.0), and low maternal education (OR: 1.6, 95% CI: 1.4-1.8). 66.7% (66.6%-66.8%) of the children had 2 or more leading risk factors simultaneously. Simultaneous presence of multiple leading risk factors was significantly associated with elevated risk of U5M and children presenting with all 5 leading risk factors exhibited an exceedingly high risk of U5M (OR: 5.2, 95% CI: 4.3-6.3); a dose-response relationship between the number of risk factors and U5M was also observed-with the increment of numbers of leading risk factors, the U5M showed an increasing trend (p-trend < 0.001). Interpretation: Exposure to multiple risk factors is very common in LMICs and underscores the necessity of developing multisectoral and integrated approaches to accelerate progress in reducing U5M in line with the SDG 3.2. Funding: This research is funded by Research Fund, Vanke School of Public Health, Tsinghua University.

Association Between Parental Education and Simultaneous Malnutrition Among Parents and Children in 45 Low- and Middle-Income Countries.

Importance: Parental education is known to be associated with the health status of parents and their offspring. However, the association between parental education and the simultaneous manifestation of multiple forms of malnutrition within households remains underinvestigated globally. Objective: To assess the association between parental education and the simultaneous manifestation of malnutrition of both parent and child (either overnutrition or undernutrition)-referred to as the double burden of malnutrition (DBM)-at the household level in mother-child and father-child pairs in low- and middle-income countries (LMICs). Design, Setting, and Participants: This cross-sectional study used data from the US Agency for International Development Demographic and Health Surveys (January 1, 2010, to December 31, 2021) to identify mother-child pairs and father-child pairs from LMICs. The eligibility criteria were as follows: (1) children aged 0 to 59 months; (2) nonpregnant mothers at the time of the survey in the sample of mother-child pairs; and (3) valid measures of the weight, height, and hemoglobin level for the child and at least 1 of their parents. Exposures: Highest level of parental education obtained and number of years of education completed. Main Outcomes and Measures: Four sets of multivariable logistic regression models were constructed to assess the association between parental education and DBM, and analysis was performed between March 10 and May 15, 2022. Results: This study included 423 340 mother-child pairs from 45 LMICs and 56 720 father-child pairs from 16 LMICs. The mean (SD) age of the mother-child pairs was 28.2 (6.1) and 1.9 (1.4) years, respectively; 48.8% of the children were female. We observed that 49.0% of mother-child pairs experienced DBM. Compared with mother-child pairs with no maternal education, higher maternal education was associated with a lower risk of DBM. For example, the odds ratio (OR) for tertiary maternal education was 0.71 (95% CI, 0.67-0.74). However, the association differed by DBM subtypes: higher maternal education was associated with a lower risk of both mothers and children being undernourished but with a higher risk of almost all DBM subtypes involving overnutrition. For example, compared with mother-child pairs with no maternal education, those with secondary education were less likely to develop simultaneous maternal and child undernutrition (OR, 0.83 [95% CI, 0.80-0.86]) but were more likely to experience simultaneous maternal and child overnutrition (OR, 2.20 [95% CI, 1.61-3.00]); similar results were observed for pairs with primary and tertiary education. The results in mother-child pairs remained consistent after controlling for paternal education. Among the father-child pairs, 26.5% had DBM, with fathers with tertiary education significantly more likely to experience simultaneous paternal overnutrition and child undernutrition (OR, 1.55 [95% CI, 1.23-1.95]) compared with pairs with no paternal education; they were also less likely to have both paternal and child undernutrition (OR, 0.70 [95% CI, 0.59-0.84]). Conclusions and Relevance: In this study, maternal education and paternal education were independently associated with DBM, and the associations differed by DBM subtypes. These findings suggest that the different risks of malnutrition faced by households with various levels of education should thus be considered in policy evaluation.

The effect of a disability-targeted cash transfer program on universal health coverage and universal access to education: a nationwide cohort study of Chinese children and adolescents with disabilities.

Background: To achieve improved outcomes for children and adolescents with disabilities, it is central to have universal health coverage (UHC) and universal access to education. This study investigates whether a disability-targeted cash transfer (CT) program is associated with improved access to healthcare and education for children and adolescents with disabilities. Methods: We used nationwide survey data of two million children and adolescents living with disabilities, who aged 8-15 years when entering the cohort between January 1, 2015, and December 31, 2019. With a quasi-experimental study design, we compared the outcomes between CT beneficiaries who newly received CT benefits during the study period and non-beneficiaries who were disabled but never received CT using logistic regressions after propensity score matching with a 1:1 ratio. Outcomes of interest were utilization of rehabilitation services in the past year, medical treatment if the individual had illness in the past two weeks, school attendance if not in school at the start of the study, and reported financial hardship to access these services. Findings: Of the total cohort, 368,595 children and adolescents fit the inclusion criteria, including 157,707 new CT beneficiaries and 210,888 non-beneficiaries. After matching, CT beneficiaries showed 2.27 (95% confidence interval [CI]: 2.23, 2.31) higher odds of utilizing rehabilitation services and 1.34 (95% CI: 1.23, 1.46) higher odds of getting medical treatment compared to non-beneficiaries. CT benefits were also significantly associated with less report of financial barrier to access rehabilitation services (odds ratio [OR]: 0.63, 95% CI: 0.60, 0.66) and medical treatment (OR: 0.66, 95% CI: 0.57, 0.78). Moreover, CT program was associated with higher odds of school attendance (OR: 1.99, 95% CI: 1.85, 2.15) and lower odds of reporting financial difficult to access education (OR: 0.41, 95% CI: 0.36, 0.47). Interpretation: Our results suggest that the receipt of CT was associated with improved access to health and educational resources. This finding provides supporting evidence for the identification of efficient and feasible interventions to move toward UHC and universal education under the Sustainable Development Goals. Funding: This research was supported by Sanming Project of Medicine in Shenzhen (NO.SZSM202111001), China National Natural Science Foundation (Grant/Award Number: 72274104, 71904099) and Tsinghua University Spring Breeze Fund (20213080028).

The association of a disability-targeted cash transfer programme with disability status and health-care access: a quasi-experimental study using a nationwide cohort of 4·3 million Chinese adults living with severe disabilities.

BACKGROUND: Cash transfer is a crucial policy tool to address inequality. The objective of this study was to investigate the association between China's disability-targeted cash transfer programme and disability status, as well as equitable access to rehabilitation and medical services. METHODS: For this quasi-experimental study, we drew data from the nationwide administrative cohort of individuals with disabilities between Jan 1, 2015, and Dec 31, 2019. Individuals were enrolled in the cohort if they were aged 18 years or older, had severe disabilities as defined by the Chinese Government, and had available cash transfer information for at least 4 consecutive years, without having started receiving cash transfer benefits at the time of enrolment. We used a quasi-experimental design with propensity score matching to estimate the effects of cash transfers on disability status, access to rehabilitation services, and access to medical treatment. The primary outcomes were development of new disability and reduction of existing disabilities. Secondary outcomes were use of rehabilitation services, financial barriers as a major obstacle to accessing rehabilitation services, use of medical services by individuals who had an illness in the previous 2 weeks, and financial barriers as a major obstacle to accessing medical services. FINDINGS: From an initial pool of 51 356 125 individuals with disabilities registered in the administrative system, 2 686 024 individuals were eligible for analysis, of whom 2 165 335 (80·6%) were cash transfer beneficiaries and 520 689 (19·4%) non-beneficiaries. After propensity score matching, the cohort included 4 330 122 adults with severe disabilities. Cash transfer beneficiaries had significantly lower odds of developing new disabilities over time than non-beneficiaries (odds ratio [OR] 0·90, 95% CI 0·86-0·94; p<0·0001) and higher odds of having a reduced number of disabilities over time (1·17, 1·10-1·25; p<0·0001). Compared with non-beneficiaries, cash transfer beneficiaries were more likely to use rehabilitation services (2·12, 2·11-2·13; p<0·0001) and medical services (1·74, 1·69-1·78; p<0·0001), and less likely to report financial hardship to access rehabilitation services (0·53, 0·52-0·54; p<0·0001) and medical services (0·88, 0·84-0·93; p<0·0001) at the study endpoint. INTERPRETATION: The receipt of cash transfers was associated with improved disability status and increased access to disability-related services. The findings suggest that cash transfers could be a potential method for promoting universal health coverage among individuals living with disabilities. FUNDING: China National Natural Science Foundation.

Global determination of reaction rates and lipid turnover kinetics in Mus musculus.

Metabolism is fundamental to life, but measuring metabolic reaction rates remains challenging. Here, we applied C13 fluxomics to monitor the metabolism of dietary glucose carbon in 12 tissues, 9 brain compartments, and over 1,000 metabolite isotopologues over a 4-day period. The rates of 85 reactions surrounding central carbon metabolism are determined with elementary metabolite unit (EMU) modeling. Lactate oxidation, not glycolysis, occurs at a comparable pace with the tricarboxylic acid cycle (TCA), supporting lactate as the primary fuel. We expand the EMU framework to track and quantify metabolite flows across tissues. Specifically, multi-organ EMU simulation of uridine metabolism shows that tissue-blood exchange, not synthesis, controls nucleotide homeostasis. In contrast, isotopologue fingerprinting and kinetic analyses reveal the brown adipose tissue (BAT) having the highest palmitate synthesis activity but no apparent contribution to circulation, suggesting a tissue-autonomous synthesis-to-burn mechanism. Together, this study demonstrates the utility of dietary fluxomics for kinetic mapping in vivo and provides a rich resource for elucidating inter-organ metabolic cross talk.