Branched-chain amino acids and the risks of dementia, Alzheimer's disease, and Parkinson's disease.

Background: We aimed to examine the association between blood levels of Branched-chain amino acids (BCAAs) - specifically isoleucine, leucine, and valine - and the susceptibility to three neurodegenerative disorders: dementia, Alzheimer's disease (AD), and Parkinson's disease (PD). Methods: Based on data from the UK Biobank, a Cox proportional hazard regression model and a dose-response relationship were used to analyze the association between BCAAs and the risks of dementia, AD, and PD. We also generated a healthy lifestyle score and a polygenic risk score. Besides, we conducted a sensitivity analysis to ensure the robustness of our findings. Results: After adjusting for multiple covariates, blood concentrations of isoleucine, leucine, and valine were significantly associated with a reduced risk of dementia and AD. This association remained robust even in sensitivity analyses. Similarly, higher levels of isoleucine and leucine in the blood were found to be associated with an increased risk of PD, but this positive correlation could potentially be explained by the presence of covariates. Further analysis using a dose-response approach revealed that a blood leucine concentration of 2.14 mmol/L was associated with the lowest risk of dementia. Conclusion: BCAAs have the potential to serve as a biomarker for dementia and AD. However, the specific mechanism through which BCAAs are linked to the development of dementia, AD, and PD remains unclear and necessitates additional investigation.

Potassium affects the association between dietary intake of vitamin C and NAFLD among adults in the United States.

INTRODUCTION: Although the association between nonalcoholic fatty liver disease (NAFLD) and vitamin C has been well studied, the effects of dietary potassium intake on this relationship are still unclear. Thus, this study aimed to determine the effects of dietary potassium intake on the association between vitamin C and NAFLD. METHODS: We performed a cross-sectional learn about with 9443 contributors the usage of 2007-2018 NHANES data. Multiple logistic regression evaluation has been utilized to check out the affiliation of dietary vitamin C intake with NAFLD and advanced hepatic fibrosis (AHF). Subsequently, we plotted a smoothed match curve to visualize the association. Especially, the analysis of AHF was conducted among the NAFLD population. In addition, stratified evaluation used to be developed primarily based on demographic variables to verify the steadiness of the results. Effect amendment by way of dietary potassium intake used to be assessed via interplay checks between vitamin C and NAFLD in the multivariable linear regression. RESULTS: In this cross-sectional study, we found that vitamin C was negatively related to NAFLD and AHF. The relationship between vitamin C and NAFLD was different in the low, middle and high potassium intake groups. Furthermore, potassium intake significantly modified the negative relationship between vitamin C and NAFLD in most of the models. CONCLUSION: Our research showed that potassium and vitamin C have an interactive effect in reducing NAFLD, which may have great importance for clinical medication.

UPLC-ESI-MS/MS-based widely targeted metabolomics reveals differences in metabolite composition among four Ganoderma species.

The Chinese name "Lingzhi" refers to Ganoderma genus, which are increasingly used in the food and medical industries. Ganoderma species are often used interchangeably since the differences in their composition are not known. To find compositional metabolite differences among Ganoderma species, we conducted a widely targeted metabolomics analysis of four commonly used edible and medicinal Ganoderma species based on ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Through pairwise comparisons, we identified 575-764 significant differential metabolites among the species, most of which exhibited large fold differences. We screened and analyzed the composition and functionality of the advantageous metabolites in each species. Ganoderma lingzhi advantageous metabolites were mostly related to amino acids and derivatives, as well as terpenes, G. sinense to terpenes, and G. leucocontextum and G. tsugae to nucleotides and derivatives, alkaloids, and lipids. Network pharmacological analysis showed that SRC, GAPDH, TNF, and AKT1 were the key targets of high-degree advantage metabolites among the four Ganoderma species. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes demonstrated that the advantage metabolites in the four Ganoderma species may regulate and participate in signaling pathways associated with diverse cancers, Alzheimer's disease, and diabetes. Our findings contribute to more targeted development of Ganoderma products in the food and medical industries.

Sunlight-driven and gram-scale vanillin production via Mn-defected γ-MnO2 catalyst in aqueous environment.

The production of vanillin from biomass offers a sustainable route for synthesizing daily-use chemicals. However, achieving sunlight-driven vanillin synthesis through H2O activation in an aqueous environment poses challenges due to the high barrier of H2O dissociation. In this study, we have successfully developed an efficient approach for gram-scale vanillin synthesis in an aqueous reaction, employing Mn-defected γ-MnO2 as a photocatalyst at room temperature. Density functional theory calculations reveal that the presence of defective Mn species (Mn3+) significantly enhances the adsorption of vanillyl alcohol and H2O onto the surface of the γ-MnO2 catalyst. Hydroxyl radical (˙OH) species are formed through H2O activation with the assistance of sunlight, playing a pivotal role as oxygen-reactive species in the oxidation of vanillyl alcohol into vanillin. The Mn-defected γ-MnO2 catalyst exhibits exceptional performance, achieving up to 93.4% conversion of vanillyl alcohol and 95.7% selectivity of vanillin under sunlight. Notably, even in a laboratory setting during the daytime, the Mn-defected γ-MnO2 catalyst demonstrates significantly higher catalytic performance compared to the dark environment. This work presents a highly effective and promising strategy for low-cost and environmentally benign vanillin synthesis.

Gemfibrozil-Platinum(IV) Precursors for New Enhanced-Starvation and Chemotherapy In Vitro and In Vivo.

A brand-new enhanced starvation is put forward to trigger sensitized chemotherapy: blocking tumor-relation blood vessel formation and accelerating nutrient degradation and efflux. Following this concept, two cisplatin-like gemfibrozil-derived Pt(IV) prodrugs, GP and GPG, are synthesized. GP and GPG had nanomolar IC50 against A2780 cells and higher selectivity against normal cells than cisplatin. Bioactivity results confirmed that GP and GPG highly accumulated in cells and induced DNA damage, G2-phase arrest, and p53 expression. Besides, they could increase ROS and MDA levels and reduce mitochondrial membrane potential and Bcl-2 expression to promote cell apoptosis. In vivo, GP showed superior antitumor activity in A2780 tumor-bearing mice with no observable tissue damage. Mechanistic studies suggested that highly selective chemotherapy could be due to the new enhanced starvation effect: blocking vasculature formation via inhibiting the CYP2C8/EETs pathway and VEGFR2, NF-κB, and COX-2 expression and cholesterol efflux and degradation acceleration via increasing ABCA1 and PPARα.

MSLN induced EMT, cancer stem cell traits and chemotherapy resistance of pancreatic cancer cells.

Chemoresistance is one of the main reasons for poor prognosis of pancreatic cancer. The effects of mesothelin (MSLN) on chemoresistance in pancreatic cancer are still unclear. We aim to investigate potential roles of MSLN in chemoresistance and its relationship with proliferation, epithelial-mesenchymal transition (EMT) and cancer stemness of pancreatic cancer cells. Human pancreatic cancer cell lines ASPC-1 and Mia PaCa-2 with high and low expression of MSLN, respectively, were selected. The ASPC-1 with MSLN knockout (KO) and Mia PaCa-2 of MSLN overexpression (OE) were generated. The effects of MSLN on cell phenotypes, expression of EMT-related markers, clone formation, tumor sphere formation, and pathologic role of MSLN in tumorigenesis were detected. Sensitivity of tumor cells to gemcitabine was evaluated. The results showed that adhesion, proliferation, migration and invasion were decreased significantly in ASPC-1 with MSLN KO, whereas increased significantly in Mia PaCa-2 with MSLN OE. The size and the number of clones and tumor spheres were decreased in ASPC-1 with MSLN KO, and increased in Mia PaCa-2 with MSLN OE. In xenograft model, tumor volume was decreased (tumor grew slower) in MSLN KO group compared to control group, while increased in MSLN OE group. Mia PaCa-2 with MSLN OE had a higher IC50 of gemcitabine, while ASPC-1 with MSLN KO had a lower IC50. We concluded that MSLN could induce chemoresistance by enhancing migration, invasion, EMT and cancer stem cell traits of pancreatic cancer cells. Targeting MSLN could represent a promising therapeutic strategy for reversing EMT and chemoresistance in pancreatic cancer cells.

Punicalagin attenuates hyperuricemia via restoring hyperuricemia-induced renal and intestinal dysfunctions.

INTRODUCTION: It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown. OBJECTIVE: To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. METHODS: The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia. RESULTS: PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated via the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression via inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice. CONCLUSION: This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.

Ultrasensitive and specific photoelectrochemical sensor for hydrogen peroxide detection based on pillar[5]arene-functionalized Au nanoparticles and MWNTs hybrid BiOBr heterojunction.

A photoelectrochemical sensor for target detection of hydrogen peroxide was designed based on a new heterojunction nanocomposite which was sulfhydryl-borate ester-modified A1/B1-type pillar[5]arene (BP5)-functionalized Au NPs and multi-walled carbon nanotubes hybridized with bismuth bromide oxide (Au@BP5/MWNTs-BiOBr). The specific sensor was based on the direct induction of oxidation by hydrogen peroxide of the borate ester group of pillar[5]arene. Additionally, the local surface plasmon resonance (LSPR) of Au NPs enhanced visible light capture, the host-guest complexation of BP5 with H2O2 enhanced photocurrent response, the layer-by-layer stacked nanoflower structure of BiOBr provided large specific surface area with more active sites, and the conductivity of MWNTs enhanced the charge separation efficiency and significantly improves the stability of PEC. Their synthesis effect significantly increased the photocurrent signal and further enhanced the detection result. Under the optimal conditions, the linear concentration range of H2O2 detected by the Au@BP5/MWNTs-BiOBr sensor was from 1 to 60 pmol/L. The limit of detection (LOD) and the limit of quantification (LOQ) of the method were 0.333 pmol/L and 1 pmol/L, respectively, and the sensitivity was 6.471 pmol/L. Importantly, the PEC sensor has good stability, reproducibility, and interference resistance and can be used for the detection of hydrogen peroxide in real cells.

Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models.

Hypertrophic scar formation is influenced by the intricate interplay between fibroblasts and endothelial cells. In this study, we investigated this relationship using in vitro and in vivo models. Clinical observations revealed distinct morphological changes and increased vascularity at pathological scar sites. Further analysis using OCTA, immunohistochemistry, and immunofluorescence confirmed the involvement of angiogenesis in scar formation. Our indirect co-culture systems demonstrated that endothelial cells enhance the proliferation and migration of fibroblasts through the secretion of cytokines including VEGF, PDGF, bFGF, and TGF-ß. Additionally, a suspended co-culture multicellular spheroid model revealed molecular-level changes associated with extracellular matrix remodeling, cellular behaviors, inflammatory response, and pro-angiogenic activity. Furthermore, KEGG pathway analysis identified the involvement of TGF-ß, IL-17, Wnt, Notch, PI3K-Akt, and MAPK pathways in regulating fibroblasts activity. These findings underscore the critical role of fibroblasts-endothelial cells crosstalk in scar formation and provide potential targets for therapeutic intervention. Understanding the molecular mechanisms underlying this interplay holds promise for the development of innovative approaches to treat tissue injuries and diseases.

Impact of age, sex, and thyroid autoimmunity on the association between selenium intake and type 2 diabetes mellitus.

BACKGROUND: The association between dietary selenium(Se) intake and type 2 diabetes mellitus (T2DM) remains controversial. The present study aimed to investigate this association using data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2007-2012. METHODS: Three thousand seventy three individuals aged 20 years and above were eligible for inclusion in this cross-sectional study. The average age of the participants was 50.74 years and the proportions of males and females were nearly equal (49.12% vs. 50.88%). The odds ratios (OR) of the association between dietary Se intake (log2-transformed) and T2DM were examined through the multivariate logistic regression model. Subgroup analyses were conducted based on age, sex, and thyroid autoimmunity to assess the potential impact of these variables on the relationship. Fitted smoothing curves and threshold effect analysis were conducted to describe the nonlinear relationship. RESULTS: In the fully adjusted model, a significant positive association between Se intake and T2DM was observed (OR = 1.49, 95% CI: 1.16, 1.90, p = 0.0017). After stratifying the data by age, sex, and thyroid autoimmunity, a significant positive association between Se intake and T2DM was observed in individuals under 65 years of age, males, and those with negative thyroid autoimmunity. A two-segment linear regression model was analyzed for sex stratification, revealing a threshold effect in males with an inflection point of 90.51 µg, and an inverted U-shaped relationship in females with an inflection point of 109.90 µg, respectively. CONCLUSIONS: The present study found a positive relationship between Se intake and the prevalence of T2DM. This association is particularly significant in younger individuals, males, and those with negative thyroid autoimmunity. Our results should be validated in future large prospective studies in different populations.

Characterization and Implications of IncP-2A Plasmid pMAS152 Harboring Multidrug Resistance Genes in Extensively Drug-Resistant Pseudomonas aeruginosa.

Bacterial antimicrobial resistance (AMR) poses a significant global public health challenge. The escalation of AMR is primarily attributed to the horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs), often facilitated by plasmids. This underscores the critical need for a comprehensive understanding of the resistance mechanisms and transmission dynamics of these plasmids. In this study, we utilized in vitro drug sensitivity testing, conjugation transfer assays, and whole-genome sequencing to investigate the resistance mechanism of an extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolate, MAS152. We specifically focused on analyzing the drug-resistant plasmid pMAS152 it harbors and its potential for widespread dissemination. Bioinformatics analysis revealed that MAS152 carries a distinct IncpP-2A plasmid, pMAS152, characterized by a 44.8 kb multidrug resistance (MDR) region. This region houses a 16S rRNA methyltransferase (16S-RMTase) gene, rmtB, conferring high-level resistance to aminoglycoside antibiotics. Notably, this region also contains an extended-spectrum ß-Lactamase (ESBL) gene, blaPER-1, and an efflux pump operon, tmexCD-oprJ, which mediate resistance to ß-Lactams and quinolone antibiotics, respectively. Such a combination of ARGs, unprecedented in reported plasmids, could significantly undermine the effectiveness of first-line antibiotics in treating P. aeruginosa infections. Investigation into the genetic environment of the MDR region suggests that Tn2 and IS91 elements may be instrumental in the horizontal transfer of rmtB. Additionally, a complex Class I integron with an ISCR1 structure, along with TnAs1, seems to facilitate the horizontal transfer of blaPER-1. The conjugation transfer assay, coupled with the annotation of conjugation-related genes and phylogenetic analysis, indicates that the plasmid pMAS152 functions as a conjugative plasmid, with other genus Pseudomonas species as potential hosts. Our findings provide vital insights into the resistance mechanisms and transmission potential of the XDR P. aeruginosa isolate MAS152, underlining the urgent need for novel strategies to combat the spread of AMR. This study highlights the complex interplay of genetic elements contributing to antibiotic resistance and underscores the importance of continuous surveillance of emerging ARGs in clinical isolates.

Evaluating the hypolipidemic effect of garlic essential oil encapsulated in a novel double-layer delivery system.

The limited application of garlic essential oil (GEO) is attributed to its pungent taste, poor water solubility and low bioavailability. Liposomes are nontoxic, biodegradable and biocompatible, and ß-cyclodextrin can inhibit undesirable odors and improve the stability and bioavailability. Thus a promising dual-layer GEO ß-cyclodextrin inclusion compound liposome (GEO-DCL) delivery system with both advantages was designed and prepared in this study. Experimental results indicated that the encapsulation efficiency of GEO-DCLs was 5% higher than that of GEO liposomes (GEO-CLs), reaching more than 88%. In vitro release experiment showed that the release rate of GEO in GEO-DCLs was 40% lower than that of GEO-CLs after incubation in gastric juice for 6-h, indicating that the stability of GEO-DCLs was better than GEO-CLs. Evaluation of the effects of GEO-DCLs on lowering blood lipid levels in hypercholesterolemia mice. GEO-DCLs could reduce the weight and fat deposition in hypercholesterolemia mice. Inhibiting the increase of TC, LDL-C, and decrease of HDL-C in mice. The degree of liver injury was decreased, the number of round lipid droplets in liver cytoplasm was reduced, and the growth of fat cells was inhibited. The lipid-lowering effects of GEO-DCLs were dose-dependent. GEO-DCL can improve the bioavailability of GEO and improve dyslipidemia. Based on GEO's efficacy in lowering blood lipids, this study developed a kind of GEO-DCL compound pomegranate juice beverage with good taste, miscibility and double effect of reducing blood lipids. This study lays a foundation for the application of GEO in the field of functional food.

The molecular mechanism of action for the potent antitumor component extracted using supercritical fluid extraction from Croton crassifolius root.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Croton crassifolius has been used as a traditional Chinese medicine (TCM), called Radix Croton Crassifolius, and commonly known as "Ji Gu Xiang" in Chinese. Its medicinal value has been recorded in several medical books or handbooks, such as "Sheng Cao Yao Xing Bei Yao", "Ben Cao Qiu Yuan" and "Zhong Hua Ben Cao". It has been traditional employed for treating sore throat, stomach-ache, rheumatism and cancer. AIM OF THE STUDY: At present, there are limited studies on the evaluation of low-polarity extracts of roots in C. crassifolius. Consequently, the aim of this study was to evaluate the antitumor effect of the low-polarity extract of C. crassifolius root. MATERIALS AND METHODS: Extracts were obtained by supercritical fluid extraction. The extracts were tested for antitumor effects in vitro on several cancer cell lines. A CCK-8 kit was used for further analysis of cell viability. A flow cytometer and propidium iodide staining were used to evaluate the cell cycle and apoptosis. Hoechst staining, JC-1 staining and the fluorescence probe DCFH-DA were used to evaluate apoptotic cells. Molecular mechanisms of action were analyzed by quantitative RT‒PCR and Western blotting. Immunohistochemistry was used for the evaluation of xenograft tumors in male BALB/c mice. Finally, molecular docking was employed to predict the bond between the desired bioactive compound and molecular targets. RESULTS: Eleven diterpenoids were isolated from low-polarity C. crassifolius root extracts. Among the compounds, chettaphanin II showed the strongest activity (IC50 = 8.58 µM) against A549 cells. Evaluation of cell viability and the cell cycle showed that Chettaphanin II reduced A549 cell proliferation and induced G2/M-phase arrest. Chttaphanin II significantly induced apoptosis in A549 cells, which was related to the level of apoptosis-related proteins. The growth of tumor tissue was significantly inhibited by chettaphanin II in experiments performed on naked mice. The antitumor mechanism of chettaphanin II is that it can obstruct the mTOR/PI3K/Akt signaling pathway in A549 cells. Molecular docking established that chettaphanin II could bind to the active sites of Bcl-2 and Bax. CONCLUSIONS: Taken together, the natural diterpenoid chettaphanin II was identified as the major antitumor active component, and its potential for developing anticancer therapies was demonstrated for the first time by antiproliferation evaluation in vitro and in vivo.

Dual-functional ionic liquids additive enables dendrite-free Zn anode with ultra-long cycle life over one year.

Zn anodes suffer from the formation of uncontrolled dendrites aggravated by the uneven electric field and the insulating by-product accumulation in aqueous zinc-ion batteries (AZIBs). Here, an effective strategy implemented by 1-butyl-3-methylimidazolium hydrogen sulfate (BMIHSO4) additive is proposed to synergistically tune the crystallographic orientation of zinc deposition and suppress the formation of zinc hydroxide sulfate for enhancing the reversibility on Zn anode surface. As a competing cation, BMI+ is proved to preferably adsorb on Zn-electrode compared with H2O molecules, which shields the "tip effect" and inhibits the Zn-deposition agglomerations to inducing the horizontal growth along Zn (002) crystallographic texture. Simultaneously, the protonated BMIHSO4 additives could remove the detrimental OH- in real-time to fundamentally eliminate the accumulation of 6Zn(OH)2·ZnSO4·4H2O and Zn4SO4(OH)6·H2O on Zn anode surface. Consequently, Zn anode exhibits an ultra-long cycling stability of one year (8762 h) at 0.2 mA cm-2/0.2 mAh cm-2, 3600 h at 2 mA cm-2/2 mAh cm-2 with a high plating cumulative capacity of 3.6 Ah cm-2, and a high average Coulombic efficiency of 99.6 % throughout 1000 cycles. This work of regulating Zn deposition texture combined with eliminating notorious by-products could offer a desirable way for stabilizing the Zn-anode/electrolyte interface in AZIBs.

Enzyme-induced reactive oxygen species trigger oxidative degradation of sulfamethoxazole within a methanotrophic biofilm.

Although microorganisms carrying copper-containing membrane-bound monooxygenase (CuMMOs), such as particulate methane monooxygenase (pMMO) and ammonia monooxygenase (AMO), have been extensively documented for their capability to degrade organic micropollutants (OMPs), the underlying reactive mechanism remains elusive. In this study, we for the first time demonstrate biogenic reactive oxygen species (ROS) play important roles in the degradation of sulfamethoxazole (SMX), a representative OMP, within a methane-fed biofilm. Highly-efficient and consistent SMX biodegradation was achieved in a CH4-based membrane biofilm reactor (MBfR), manifesting a remarkable SMX removal rate of 1210.6 ± 39.0 µg·L-1·d-1. Enzyme inhibition and ROS clearance experiments confirmed the significant contribution of ROS, which were generated through the catalytic reaction of pMMO and AMO enzymes, in facilitating SMX degradation. Through a combination of density functional theory (DFT) calculations, electron paramagnetic resonance (EPR) analysis, and transformation product detection, we elucidated that the ROS primarily targeted the aniline group in the SMX molecule, inducing the formation of aromatic radicals and its progressive mineralization. In contrast, the isoxazole-ring was not susceptible to electrophilic ROS attacks, leading to accumulation of 3-amino-5-methylisoxazole (3A5MI). Furthermore, microbiological analysis suggested Methylosarcina (a methanotroph) and Candidatus Nitrosotenuis (an ammonia-oxidizing archaea) collaborated as the SMX degraders, who carried highly conserved and expressed CuMMOs (pMMO and AMO) for ROS generation, thereby triggering the oxidative degradation of SMX. This study deciphers SMX biodegradation through a fresh perspective of free radical chemistry, and concurrently providing a theoretical framework for the advancement of environmental biotechnologies aimed at OMP removal.

Global, regional, and national time trends in incidence for tuberculosis, 1990-2019: An age-period-cohort analysis for the Global Burden of Disease 2019 study.

BACKGROUND: Tuberculosis (TB) represents a significant global health concern, being the leading cause of mortality from a single infectious agent worldwide. The investigation of TB incidence and epidemiological trends is critical for evaluating the effectiveness of control strategies and identifying ongoing challenges. OBJECTIVES: This study presents the trend in TB incidence across 204 countries and regions over a 30-year period. METHODS: The study utilises data sourced from the Global Burden of Disease (GBD) database. The age cohort model and gender subgroup analysis were employed to estimate the net drift (overall annual percentage change), local drift (age annual percentage change), longitudinal age curve (expected age ratio), and cycle and cohort effect (relative risk of cycle and birth cohort) of TB incidence from 1990 to 2019. This approach facilitates the examination and differentiation of age, period, and cohort effects in TB incidence trends, potentially identifying disparities in TB prevention across different countries. RESULTS: Over the past three decades, a general downward trend in TB incidence has been observed in most countries. However, in 15 of the 204 countries, the overall incidence rate is still on the rise (net drift ≥0.0 %) or stagnant decline (≥-0.5 %). From 1990 to 2019, the net drift of tuberculosis mortality ranged from -2.2 % [95 % confidence interval (CI): -2.33, -2.05] in high Socio-demographic Index (SDI) countries to -1.7 % [95 % CI: -1.81, -1.62] in low SDI countries. In some below-average SDI countries,men in the birth cohort are at a disadvantage and at risk of deterioration, necessitating comprehensive TB prevention and treatment. CONCLUSIONS: While the global incidence of TB has declined, adverse period and cohort effects have been identified in numerous countries, raising questions about the adequacy of TB healthcare provision across all age groups. Furthermore, this study reveals gender disparities in TB incidence.

Optical proximity correction of hot-spot patterns with subwavelength size in DMD maskless projection lithography.

When the critical dimension (CD) of resist patterns nears the resolution limit of the digital micromirror device (DMD) maskless projection lithography (DMD-MPL), significant distortion can emerge in the silicon wafer due to the optical proximity effect (OPE). The significant distortion (breakpoints, line-end scaling, corner rounding, etc.) between resist patterns and target patterns results in reduced lithographic quality. To address this issue, we have proposed a pixel-based optical proximity correction (PB-OPC) method used for the hot-spot patterns with subwavelength sizes specifically designed for DMD-MPL. Employing an end-to-end learning neural network, the PB-OPC algorithm is both straightforward and efficient. A well-trained U-net framework facilitates the mapping from unoptimized masks to optimized masks. Experimental exposure trials have demonstrated that this method not only corrects OPC in general patterns but also effectively rectifies hot-spot patterns. The pattern error (PE) value can be reduced by about 30% in the design layouts. We believe this approach holds the potential to enhance the resolution and fidelity of resist patterns in DMD maskless lithography.