The inhibition of VDAC1 oligomerization promotes pigmentation through the CaMK-CRTCs/CREB-MITF pathway.

The voltage-dependent anion channel 1 (VDAC1) forms an oligomeric structure on the mitochondrial outer membrane, which plays critical roles in many physiological processes. Research studies have demonstrated that the knockout of VDAC1 increases pigment content and up-regulates the expression of melanogenic genes. Due to its involvement in various physiological processes, the depletion of VDAC1 has significant detrimental effects on cellular functions and the inhibition of VDAC1 oligomerization has recently emerged as a promising strategy for the treatment of several diseases. In this study, we found that VDAC1 oligomerization inhibitors, VBIT-12 and NSC-15364, promote melanogenesis, dendrite formation and melanosome transport in human epidermal melanocytes (HEMCs). Mechanistically, treatment of HEMCs with an oligomerization inhibitor increased the level of cytoplasmic calcium ions, which activated calcium-calmodulin dependent protein kinase (CaMK) and led to the phosphorylation of CREB and the nuclear translocation of CREB-regulated transcription coactivators (CRTCs). Subsequently, CRTCs, p-CREB and CREB-binding protein (CBP) in the nucleus cooperatively recruit the transcription machinery to initiate the transcription of MITF thus promoting pigmentation. Importantly, our study also demonstrates that VDAC1 oligomerization inhibitors increase pigmentation in zebrafish and in human skin explants, highlighting their potential as a therapeutic strategy for skin pigmentation disorders.

Presenilin deficiency enhances tau phosphorylation and its secretion.

Alzheimer's disease (AD) is characterized by the accumulation of abnormally folded amyloid ß-protein (Aß) in the brain parenchyma and phosphorylated tau in neurons. Presenilin (PS, PSEN) 1 and PS2 are essential components of γ-secretase, which is responsible for the cleavage of amyloid precursor protein (APP) to generate Aß. PSEN mutations are associated with tau aggregation in frontotemporal dementia, regardless of the presence or absence of Aß pathology. However, the mechanism by which PS regulates tau aggregation is still unknown. Here, we found that tau phosphorylation and secretion were significantly increased in PS double-knock-out (PS1/2-/-) fibroblasts compared with wild-type fibroblasts. Tau-positive vesicles in the cytoplasm were significantly increased in PS1/2-/- fibroblasts. Active GSK-3ß was increased in PS1/2-/- fibroblasts, and inhibiting GSK3ß activity in PS1/2-/- fibroblasts resulted in decreased tau phosphorylation and secretion. Transfection of WT human PS1 and PS2 reduced the secretion of phosphorylated tau and active GSK-3ß in PS1/2-/- fibroblasts. However, PS1D257A without γ-secretase activity did not decrease the secretion of phosphorylated tau. Furthermore, nicastrin deficiency also increased tau phosphorylation and secretion. These results suggest that deficient PS complex maturation may increase tau phosphorylation and secretion. Thus, our studies discover a new pathway by which PS regulates tau phosphorylation/secretion and pathology independent of Aß and suggest that PS serves as a potential therapeutic target for treating neurodegenerative diseases involving tau aggregation.

The inappropriate application of imidacloprid destroys the ability of predatory natural enemies to control pests in the food chain: A case study of the feeding behavior of Orius similis on Frankliniella occidentalis.

Insecticides are an indispensable and important tool for agricultural production. However, the inappropriate application of insecticides can cause damage to the food chain and ecosystem. Orius similis is an important predatory and natural enemy of Frankliniella occidentalis. Imidacloprid is widely used to control pests, but will inevitably exert adverse effects on O. similis. In order to determine the effect of different imidacloprid treatments on the ability of O. similis to prey on the 2nd-instar nymphs of F. occidentalis, we determined the toxicity and predation of imidacloprid on different stages of O. similis under contact and ingestion treatments. In addition, we used the Holling disc equation to evaluate the ability of O. similis to search and exhibit predatory activity following contact and ingestion treatments. Analysis showed that the highest LC10 and LC20 values for imidacloprid contact and ingestion toxicity treatment were 17.06 mg/L and 23.74 mg/L, respectively. Both imidacloprid treatments led toa reduction in the predatory of O. similis on prey. The functional responses of the 3rd to 5th instar nymphs, along with female and male O. similis adults to the 2nd-instar nymphs of F. occidentalis were consistent with the Holling type II response following contact and ingestion with imidacloprid. However, following imidacloprid treatment, the handing time (Th) of O. similis with single F. occidentalis was prolonged and the instantaneous attack rate (a) was reduced after imidacloprid treatment. The predatory capacity (a/Th) of female O. similis adults when treated with the LC10 concentration of imidacloprid by ingestion was 52.85; this was lower than that of the LC10 concentration of imidacloprid in the contact treatment (57.67). The extent of predation of O. similis on the 2nd-instar nymphs of F. occidentalis was positively correlated with prey density, although the search effect was negatively correlated with prey density. The most extensive search effect was exhibited by adult O. similis females. Simulations with the Hessell-Varley interference model showed that an increase in the number of O. similis would reduce search efficiency regardless of whether they were treated with imidacloprid or not. Thus, O. similis, especially female adults, exhibited strong potential for controlling the 2nd-instar nymphs of F. occidentalis. The toxicity of ingestion following treatment with the same concentration of imidacloprid in O. similis was greater than that of contact treatment. When using O. similis to control F. occidentalis in the field, we should increase the number of female adults released, and prolong the interval between imidacloprid treatment and O. similis exposure. This strategy will improve the control ability of O. similis, coordinate both chemical and biological control, reduce the impact of pesticides on the environment, and improve the efficiency of agricultural production.

Presenilin: A Multi-Functional Molecule in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases.

Presenilin, a transmembrane protein primarily known for its role in Alzheimer's disease (AD) as part of the γ-secretase complex, has garnered increased attention due to its multifaceted functions in various cellular processes. Recent investigations have unveiled a plethora of functions beyond its amyloidogenic role. This review aims to provide a comprehensive overview of presenilin's diverse roles in AD and other neurodegenerative disorders. It includes a summary of well-known substrates of presenilin, such as its involvement in amyloid precursor protein (APP) processing and Notch signaling, along with other functions. Additionally, it highlights newly discovered functions, such as trafficking function, regulation of ferritin expression, apolipoprotein E (ApoE) secretion, the interaction of ApoE and presenilin, and the Aß42-to-Aß40-converting activity of ACE. This updated perspective underscores the evolving landscape of presenilin research, emphasizing its broader impact beyond established pathways. The incorporation of these novel findings accentuates the dynamic nature of presenilin's involvement in cellular processes, further advancing our comprehension of its multifaceted roles in neurodegenerative disorders. By synthesizing evidence from a range of studies, this review sheds light on the intricate web of presenilin functions and their implications in health and disease.

[Evolution and Application of Disease Control Priorities]. / ç–¾ç— æŽ§åˆ¶ä¼˜å ˆçš„æ¼”è¿›åŠåº”ç”¨.

Disease control priority (DCP) is an important public health intervention strategy. Diseases that should be prioritized for prevention and control are first screened with a series of criteria, including the severity of the disease burden, the effectiveness of disease control technologies, the prevention and control capacity of the existing health system, etc. Then, the prevention and control technologies for these diseases undergo qualitative evaluation (eg, face-to-face interviews, expert consultation, workshops, etc) and quantitative evaluation (eg, cost-benefit analysis, multi-criteria decision analysis, etc). Finally, the public health initiatives that should be prioritized are identified. From the conception of the idea, to the formal proposition of the concept, to guidance for practice, DCP has gone through more than 70 years of development. Through DCP, significant contributions has been made to improving the efficiency of health care service systems and promoting the health of populations in developing countries. Herein, we systematically reviewed the background, development history, realization method, and practical applications of DCP, focusing on exploring the application potential of DCP in health governance and providing technical support and decision-making reference for the comprehensive promotion of the Healthy China Initiative.

A chemo-selective enrichment strategy to achieve in-depth coverage of methyllysine proteome.

Proteomics is a powerful method to comprehensively understand cellular posttranslational modifications (PTMs). Due to low abundance, tryptic peptides with PTMs are usually enriched for enhanced coverage by LC-MS/MS. Affinity chromatography for phosphoproteomes by metal-oxide and pan-specific antibodies for lysine acetylome allow identification of tens of thousands of modification sites. Lysine methylation is a significant PTM, however, only hundreds of methylation sites were identified from available approaches. Here we report an aryl diazonium-based chemoselective strategy that enables enrichment of monomethyllysine (Kme1) peptides via covalent bond with extraordinary sensitivity. We identified more than ten thousand Kme1 peptides from diverse cell lines and mouse tissues, that implied wide lysine methylation impact on cellular processes. In addition, we found a significant amount of methyl marks that were not S-adenosyl methionine (SAM)-dependent by isotope labeling experiments. And therefore, this method paves a way to broad application in lysine methylation research and new biology discovery.

Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis.

Alzheimer's disease (AD) is a debilitating dementia characterized by progressive memory loss and aggregation of amyloid-ß (Aß) protein into amyloid plaques in patient brains. Mutations in presenilin (PS) lead to abnormal generation of Aß, which is the major cause of familial AD (FAD), and apolipoprotein E4 (ApoE4) is the major genetic risk factor for sporadic AD (SAD) onset. However, whether dysfunction of PS is involved in the pathogenesis of SAD is largely unknown. We found that ApoE secretion was completely abolished in PS-deficient cells and markedly decreased by inhibition of γ-secretase activity. Blockade of γ-secretase activity by a γ-secretase inhibitor, DAPT, decreased ApoE secretion, suggesting an important role of γ-secretase activity in ApoE secretion. Reduced ApoE secretion is also observed in nicastrin-deficient cells with reduced γ-secretase activity. PS deficiency enhanced nuclear translocation of ApoE and binding of ApoE to importin α4, a nuclear transport receptor. Moreover, the expression of PS mutants in PS-deficient cells suppressed the restoration effects on ApoE secretion compared with the expression of wild-type PS. Plasma ApoE levels were lower in FAD patients carrying PS1 mutations compared with normal control subjects. Our findings suggest a novel role of PS contributing to the pathogenesis of SAD by regulating ApoE secretion.SIGNIFICANCE STATEMENT Familial AD (FAD) typically results from mutations in the genes encoding amyloid precursor protein, presenilin 1 (PS1), or PS2. Many PS mutants have been found to exert impaired γ-secretase activity and increased amyloid-ß 42 (Aß42)/Aß40 ratio, which induce early amyloid deposition and FAD. On the other hand, apolipoprotein E4 (ApoE4) is the major genetic risk factor for sporadic AD (SAD) and contributes to AD pathogenesis because it has reduced Aß clearance capability compared with ApoE3 and ApoE2. FAD and SAD have long been considered to be caused by these two independent mechanisms; however, for the first time, we demonstrated that PS is essential for ApoE secretion and PS mutants affected ApoE secretion in vitro and in human samples, suggesting a novel mechanism by which PS is also involved in SAD pathogenesis.

Apolipoprotein E4 inhibits γ-secretase activity via binding to the γ-secretase complex.

The mechanisms of amyloid accumulation in familial Alzheimer's disease (FAD) and sporadic AD (SAD) are controversial. In FAD, mutations in presenilin (PSEN) impair γ-secretase activity and lead to abnormal amyloid ß-protein (Aß) production, thereby increasing the Aß42/40 ratio. SAD is postulated to be caused by decreased Aß clearance of apolipoprotein E4 (APOE4), the strongest risk factor for SAD. However, whether intracellular APOE4 affects Aß production is unclear. Using APOE3 and APOE4 knock-in (KI) mouse brain and primary cultured fibroblasts from these mice, in this study, we demonstrated that APOE3 and APOE4 bind to the γ-secretase complex and isoform-dependently regulate its activity and Aß production. We found that Aß40 levels and γ-secretase activity were higher in APOE knockout mouse brain than in wild-type mouse brain. APOE4-KI fibroblasts had significant lower Aß levels and γ-secretase activity but higher Aß42/40 ratio compared with APOE3-KI cells, indicating that APOE4-KI reduces Aß production by inhibiting γ-secretase activity. Interestingly, the levels of γ-secretase complex bound to APOE4 are higher than those bound to APOE3, and the levels of γ-secretase complex in the brain and fibroblasts of APOE4-KI mice were higher than those of APOE3-KI mice. Taken together, our findings demonstrate that intracellular APOE4 inhibits Aß production, more preferentially inhibits Aß40 production, and thereby induces an increase in the Aß42/40 ratio via binding to the γ-secretase complex. These results suggest a novel mechanism in which intracellular APOE4 contributes to the pathogenesis of SAD by inhibiting γ-secretase activity.

Velocity-Dependent Friction of Graphene at Electrical Contact Interfaces.

Graphene has enormous potential as a solid lubricant at sliding electrical contact interfaces of micro-/nanoelectromechanical systems that suffer severe wear. Understanding the velocity-dependent friction of graphene under different applied voltages contributes to the application of graphene in sliding electrical contact scenarios. The friction of graphene, measured by conductive atomic force microscopy, under low applied voltage increases logarithmically with sliding velocity─the same as when no voltage is applied but at a faster rate of increase. The variation of friction was explained by the thermally activated Prandtl-Tomlinson model with increased potential barrier and temperature because of the applied voltage. An opposite trend in which friction decreases with sliding velocity is observed under high applied voltage. Topography, adhesion measurements, and SEM characterization demonstrate the wear of the tip. Moreover, the tip wears more severely at low sliding velocity compared to a high sliding velocity. It was interpreted that the excessive Joule heat at the electrical contact interface under high applied voltage weakens the mechanical properties of the tip, resulting in wear and high friction. The increase in the sliding velocity could accelerate the Joule heat transfer and reduce wear and friction. The studies provide beneficial guidelines for the design of graphene-lubricated sliding electrical contact interfaces.

Highly Regio- and Diastereoselective Phosphine-Catalyzed [2 + 4] Annulation of Benzofuran-Derived Azadienes with Allyl Carbonates: Access to Spiro[benzofuran-cyclohexanes].

A novel highly regio- and diastereoselective phosphine-catalyzed [2 + 4] annulation of benzofuran-derived azadienes (BDAs) with acidic hydrogen-tethered allyl carbonates has been developed ingeniously. A range of functionalized spiro[benzofuran-cyclohexane] derivatives with two consecutive stereocenters were smoothly obtained in moderate to excellent yields under mild reaction conditions from readily available materials. Moreover, this method is a practical and scalable strategy that creates the core structural motif of the fungistatic drug, griseofulvin.

A prospective analysis of optimal total weight gain ranges and trimester-specific weight gain rates for Chinese pregnant women.

BACKGROUND: Gestational weight gain (GWG) criteria recommended by the Institute of Medicine may not be appropriate for Asians. Our aims are to investigate the association between GWG and adverse pregnancy outcomes, and to propose optimal total GWG and rates of GWG for Chinese women. METHODS: Prospective data of 51,125 mother-child pairs from 27 hospitals and community health care centers from Guizhou, Yunnan and Sichuan provinces in China between 2014 and 2018 were analyzed. Generalized Additive Models were performed to determine the associations of GWG with the risk of aggregated adverse outcomes (gestational diabetes mellitus, preeclampsia, cesarean delivery, stillbirth, preterm birth, macrosomia, large for gestational age, and small for gestational age). The range that did not exceed a 2.5% increase from the lowest risk of aggregated adverse outcomes was defined as the optimal GWG range. RESULTS: Among all participants, U-shaped prospective association was found between GWG and the risk of aggregated adverse pregnancy outcomes. The optimal GWG range of 8.2-13.0 kg was proposed for underweight, 7.3-12.5 kg for normal weight, and 2.0-9.4 kg for overweight/obese women. Meanwhile, a higher GWG rate in the first two trimesters than that in the last trimester was suggested, except for overweight/obese women. After stratified by maternal age, mothers ≥35 years were suggested to gain less weight compared to younger mothers. CONCLUSIONS: To keep a balance between maternal health and neonatal growth, optimal GWG ranges based on Asia-specific BMI categories was suggested for Chinese women with different pre-gravid BMIs and maternal ages.

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.

Role of Interfacial Water in the Tribological Behavior of Graphene in an Electric Field.

Friction properties in the electric field are important for the application of graphene as a solid lubricant in graphene-based micro/nanoelectromechanical systems. The studies based on conductive atomic force microscopy show that interfacial water between graphene and the SiO2/Si substrate affects the friction of graphene in the electric field. Friction without applying voltage remains low because the interfacial water retains a stable ice-like network. However, friction after applying voltage increases because the polar water molecules are attracted by the electric field and gather around the tip. The gathered interfacial water not only increases the deformation of graphene but is also pushed by the tip during frictional sliding, which results in the increased friction. These studies provide beneficial guidelines for the applications of graphene as a solid lubricant in the electric field.

Polyacetylene Isomers Isolated from Bidens pilosa L. Suppress the Metastasis of Gastric Cancer Cells by Inhibiting Wnt/ß-Catenin and Hippo/YAP Signaling Pathways.

(E)-7-Phenyl-2-hepten-4,6-diyn-1-ol (1) and (Z)-7-Phenyl-2-hepten-4,6-diyn-1-ol (2) are isomeric natural polyacetylenes isolated from the Chinese medicinal plant Bidens pilosa L. This study first revealed the excellent anti-metastasis potential of these two polyacetylenes on human gastric cancer HGC-27 cells and the distinctive molecular mechanisms underlying their activities. Polyacetylenes 1 and 2 significantly inhibited the migration, invasion, and adhesion of HGC-27 cells at their non-toxic concentrations in a dose-dependent manner. The results of a further mechanism investigation showed that polyacetylene 1 inhibited the expressions of Vimentin, Snail, ß-catenin, GSK3ß, MST1, YAP, YAP/TAZ, and their phosphorylation, and upregulated the expression of E-cadherin and p-LATS1. In addition, the expressions of various downstream metastasis-related proteins, such as MMP2/7/9/14, c-Myc, ICAM-1, VCAM-1, MAPK, p-MAPK, Sox2, Cox2, and Cyr61, were also suppressed in a dose-dependent manner. These findings suggested that polyacetylene 1 exhibited its anti-metastasis activities on HGC-27 cells through the reversal of the EMT process and the suppression of the Wnt/ß-catenin and Hippo/YAP signaling pathways.

Tormentic acid, a triterpenoid isolated from the fruits of Chaenomeles speciose, protected indomethacin-induced gastric mucosal lesion via modulating miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho a/MLC pathway.

CONTEXT: Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage. OBJECTIVE: To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms. MATERIALS AND METHODS: TA concentrations of 1.563-25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats. RESULTS: TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression. DISCUSSION AND CONCLUSIONS: TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment.

Transcriptomic analysis reveals process of autolysis of Kluyveromyces marxianus in vacuum negative pressure and the higher temperature.

Kluyveromyces marxianus is expected to be used in the production of yeast extracts due to its good fermentation ability and nutritional properties. Yeast autolysis is a key process to produce yeast extract and vacuum negative pressure stress can be used as an effective way to assist autolysis. However, the molecular mechanism of initiating Kluyveromyces marxianus autolysis induced by vacuum negative pressure and the higher temperature is still unclear. In this study, RNA-seq technology was performed mainly to analyze autolytic processes in Kluyveromyces marxianus strains. Considerable differentially expressed genes (DEGs) of downregulation were significantly enriched in 7 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to synthesis and transport of RNA and ribosome, which indicated that abnormal protein translations had already occurred in autolytic process. Interestingly, due to obvious change of related DEGs, endoplasmic reticulum-associated degradation (ERAD) and autophagy were activated and cell wall integrity pathway was hindered. Under the continuous influence of the external stress environment, the long-term changes of the above pathways triggered a vicious circle of gradual damage to yeast cells, which is the main cause of yeast autolysis. These results may provide important clues for the in-depth interpretation of the yeast autolytic mechanism.

Nonsuicidal self-injury behaviour in a city of China and its association with family environment, media use and psychopathology.

INTRODUCTION: It is not clear whether there are differences in the risk factors for nonsuicidal self-injury (NSSI) between children and early adolescents. Clarifying this question is crucial for identifying actionable prevention strategies for NSSI in these two age groups. METHOD: The study, comprising 8611 children and early adolescents (4409 (51.2%) children, 4202 (48.8%) early adolescents), was based on the baseline data of the Chengdu Positive Child Development (CPCD) in China. NSSI behaviours, emotional and behavioural problems and family environment were assessed and obtained via self-reports and parent reports. RESULTS: Overall, 2520 (29.26%) participants reported having ever engaged in NSSI. There was a higher lifetime NSSI rate in males than in females during childhood, contrasting with higher NSSI rates in females than in males during early adolescence. Furthermore, NSSI shared similar risk factors, including major family conflict and poor relationships with caregivers, in both age groups. Specifically, in children, the risk of NSSI increased along with thought and attention problems (OR, 95% CI: 1.194, 1.106-1.288 and 1.114, 1.028-1.207, respectively), whereas in early adolescents, it increased with anxiety and depressive problems (OR, 95% CI: 1.259, 1.116-1.422). CONCLUSIONS: The findings suggested the need for difference in preventive strategies for NSSI in the two age groups. It may be more efficacious to screen for NSSI in children with thought and attention problems and in early adolescents with anxiety and depressive problems.

Associations of Chinese diagnosis-related group systems with inpatient expenditures for older people with hip fracture.

BACKGROUND: Hip fracture is frequent in older people and represents a major public health issue worldwide. The increasing incidence of hip fracture and the associated hospitalization costs place a significant economic burden on older patients and their families. On January 1, 2018, the Chinese diagnosis-related group (C-DRG) payment system, which aims to reduce financial barriers, was implemented in Sanming City, southern China. This study aimed to evaluate the associations of C-DRG system with inpatient expenditures for older people with hip fracture. METHODS: An uncontrolled before-and-after study employed data of all the patients with hip fracture aged 60 years or older from all the public hospitals enrolled in the Sanming Basic Health Insurance Scheme from January 1, 2016 to December 31, 2018. The 'pre C-DRG sample' included patients from January 1, 2016 to December 31, 2017. The 'post C-DRG sample' included patients from January 1, 2018 to December 31, 2018. A propensity score matching analysis was used to adjust the difference in baseline characteristic parameters between the pre and post samples. Data were analyzed using generalized linear models adjusted for the demographic, clinical, and institutional factors. Robust tests were performed by accounting for time trend, the fixed effects of the year and hospitals, and clustering effect within hospitals. RESULTS: After propensity score matching, we obtained two homogeneous groups of 1123 patients each, and the characteristic variables of the two matched groups were similar. We found that C-DRG reform was associated with a 19.51% decrease in out-of-pocket (OOP) payments (p < 0.001) and a 99.93% decrease in OOP payments as a share of total inpatient expenditure (p < 0.001); whereas total inpatient expenditure was not significantly associated with the C-DRG reform. All the sensitivity analyses did not change the results significantly. CONCLUSION: The implementation of C-DRG payment system reduced both the absolute amount of OOP payments and OOP payments as a share of total inpatient expenditure for older patients with hip fracture, without affecting total inpatient expenditure. These results may provide significant insights for policymakers in reducing the financial burden on older patients with hip fracture in other countries.

Development of the Chinese preschooler dietary index: a tool to assess overall diet quality.

BACKGROUND: Diet quality in early childhood has a long-term impact on health outcomes. However, there are scarce dietary indexes for Chinese preschool children, and the existing indexes had limited validity and reliability. This study thus aimed to develop a dietary index for preschool children based on the Chinese Dietary Guideline and Chinese Dietary Reference Intakes and to assess their overall diet quality using the China Health and Nutrition Survey (CHNS). METHODS: The Chinese Preschooler Dietary Index (CPDI) included 11 components, covering 9 food group components and two nutrient components. The total scores of CPDI ranged from 0 to 90, with a higher score indicating greater diet quality. This study assessed the diet quality of 1742 preschoolers aged two to five years old from CHNS using the CPDI. Dietary intake data were obtained using three-day 24-h diet recalls, and sociodemographic information was also collected. Cochran-Mantel-Haensel (CMH) test was used to explore the association between demographic and CPDI total scores. The principal component analysis, correlation analysis and Cronbach's alpha were used to evaluate the relative reliability and validity of the CPDI. Finally, a stepwise multiple regression analysis was performed to explore potential influencing factors of CPDI. RESULTS: Among the 1742 CHNS preschool children, more than 70% resided in rural areas and 41.2% of the sample were raised in a low-income family. The mean CPDI score of the preschoolers was 38.8 ± 12.9. Higher diet scores were correlated with higher energy and nutrient intake. Children with higher age (ß = 0.93, SE = 0.26, P = 0.0003), raised in a home with higher household income (ß = 3.11, SE = 0.27, P < 0.0001) or living in urban areas (ß = -4.44, SE = 0.66, P < 0.0001) were associated with higher CPDI scores. CONCLUSIONS: The CPDI is useful in evaluating the diet quality of preschool children. Based on the CPDI, the diet quality of Chinese preschoolers needs to be improved, especially in rural areas.

Airborne Radar Anti-Jamming Waveform Design Based on Deep Reinforcement Learning.

Airborne radars are susceptible to a large number of clutter, noise and variable jamming signals in the real environment, especially when faced with active main lobe jamming, as the waveform shortcut technology in the traditional regime can no longer meet the actual battlefield radar anti-jamming requirements. Therefore, it is necessary to study anti-main-lobe jamming techniques for airborne radars in complex environments to improve their battlefield survivability. In this paper, we propose an airborne radar waveform design method based on a deep reinforcement learning (DRL) algorithm under clutter and jamming conditions, after previous research on reinforcement-learning (RL)-based airborne radar anti-jamming waveform design methods that have improved the anti-jamming performance of airborne radars. The method uses a Markov decision process (MDP) to describe the complex operating environment of airborne radars, calculates the value of the radar anti-jamming waveform strategy under various jamming states using deep neural networks and designs the optimal anti-jamming waveform strategy for airborne radars based on the duelling double deep Q network (D3QN) algorithm. In addition, the method uses an iterative transformation method (ITM) to generate the time domain signals of the optimal waveform strategy. Simulation results show that the airborne radar waveform designed based on the deep reinforcement learning algorithm proposed in this paper improves the signal-to-jamming plus noise ratio (SJNR) by 2.08 dB and 3.03 dB, and target detection probability by 26.79% and 44.25%, respectively, compared with the waveform designed based on the reinforcement learning algorithm and the conventional linear frequency modulation (LFM) signal at a radar transmit power of 5 W. The airborne radar waveform design method proposed in this paper helps airborne radars to enhance anti-jamming performance in complex environments while further improving target detection performance.