Spatial distribution and influencing factors of CDC health resources in China: a study based on panel data from 2016-2021.

Background: Measuring the development of Chinese centers for disease control and prevention only by analyzing human resources for health seems incomplete. Moreover, previous studies have focused more on the quantitative changes in healthcare resources and ignored its determinants. Therefore, this study aimed to analyze the allocation of healthcare resources in Chinese centers for disease control and prevention from the perspective of population and spatial distribution, and to further explore the characteristics and influencing factors of the spatial distribution of healthcare resources. Methods: Disease control personnel density, disease control and prevention centers density, and health expenditures density were used to represent human, physical, and financial resources for health, respectively. First, health resources were analyzed descriptively. Then, spatial autocorrelation was used to analyze the spatial distribution characteristics of healthcare resources. Finally, we used spatial econometric modeling to explore the influencing factors of healthcare resources. Results: The global Moran index for disease control and prevention centers density decreased from 1.3164 to 0.2662 (p < 0.01), while the global Moran index for disease control personnel density increased from 0.4782 to 0.5067 (p < 0.01), while the global Moran index for health expenditures density was statistically significant only in 2016 (p < 0.1). All three types of healthcare resources showed spatial aggregation. Population density and urbanization have a negative impact on the disease control and prevention centers density. There are direct and indirect effects of disease control personnel density and health expenditures density. Population density and urbanization had significant negative effects on local disease control personnel density. Urbanization has an indirect effect on health expenditures density. Conclusion: There were obvious differences in the spatial distribution of healthcare resources in Chinese centers for disease control and prevention. Social, economic and policy factors can affect healthcare resources. The government should consider the rational allocation of healthcare resources at the macro level.

Associations between digital literacy, health literacy, and digital health behaviors among rural residents: evidence from Zhejiang, China.

OBJECTIVE: Within the digital society, the limited proficiency in digital health behaviors among rural residents has emerged as a significant factor intensifying health disparities between urban and rural areas. Addressing this issue, enhancing the digital literacy and health literacy of rural residents stands out as a crucial strategy. This study aims to investigate the relationship between digital literacy, health literacy, and the digital health behaviors of rural residents. METHODS: Initially, we developed measurement instruments aimed at assessing the levels of digital literacy and health literacy among rural residents. Subsequently, leveraging micro survey data, we conducted assessments on the digital literacy and health literacy of 968 residents in five administrative villages in Zhejiang Province, China. Building upon this foundation, we employed Probit and Poisson models to empirically scrutinize the influence of digital literacy, health literacy, and their interaction on the manifestation of digital health behaviors within the rural population. This analysis was conducted from a dual perspective, evaluating the participation of digital health behaviors among rural residents and the diversity to which they participate in such behaviors. RESULTS: Digital literacy exhibited a notably positive influence on both the participation and diversity of digital health behaviors among rural residents. While health literacy did not emerge as a predictor for the occurrence of digital health behavior, it exerted a substantial positive impact on the diversity of digital health behaviors in the rural population. There were significant interaction effects between digital literacy and health literacy concerning the participation and diversity of digital health behaviors among rural residents. These findings remained robust even after implementing the instrumental variable method to address endogeneity issues. Furthermore, the outcomes of robust analysis and heterogeneity analysis further fortify the steadfastness of the aforementioned conclusions. CONCLUSION: The findings suggest that policymakers should implement targeted measures aimed at enhancing digital literacy and health literacy among rural residents. This approach is crucial for improving rural residents' access to digital health services, thereby mitigating urban-rural health inequality.

Synthesis of Soluble High Molar Mass Poly(Phenylene Methylene)-Based Polymers.

Poly(phenylene methylene) (PPM) is a multifunctional polymer that is also active as an anticorrosion fluorescent coating material. Although this polymer was synthesized already more than 100 years ago, a versatile synthetic route to obtain soluble high molar mass polymers based on PPM has yet to be achieved. In this article, the influence of bifunctional bis-chloromethyl durene (BCMD) as a branching agent in the synthesis of PPM is reported. The progress of the reaction was followed by gel permeation chromatography (GPC) and NMR analysis. PPM-based copolymers with the highest molar mass reported so far for this class of materials (up to Mn of 205,300 g mol-1) were isolated. The versatile approach of using BCMD was confirmed by employing different catalysts. Interestingly, thermal and optical characterization established that the branching process does not affect the thermoplastic behavior and the fluorescence of the material, thus opening up PPM-based compounds with high molar mass for applications.

Exposure to microplastics renders immunity of the thick-shell mussel more vulnerable to diarrhetic shellfish toxin-producing harmful algae.

Despite both microplastics (MPs) and harmful algae blooms (HABs) may pose a severe threat to the immunity of marine bivalves, the toxification mechanism underlying is far from being fully understood. In addition, owing to the prevalence and sudden occurrence characteristics of MPs and HABs, respectively, bivalves with MP-exposure experience may face acute challenge of harmful algae under realistic scenarios. However, little is known about the impacts and underlying mechanisms of MP-exposure experience on the susceptibility of immunity to HABs in bivalve mollusks. Taking polystyrene MPs and diarrhetic shellfish toxin-producing Prorocentrum lima as representatives, the impacts of MP-exposure on immunity vulnerability to HABs were investigated in the thick-shell mussel, Mytilus coruscus. Our results revealed evident immunotoxicity of MPs and P. lima to the mussel, as evidenced by significantly impaired total count, phagocytic activity, and cell viability of haemocytes, which may result from the induction of oxidative stress, aggravation of haemocyte apoptosis, and shortage in cellular energy supply. Moreover, marked disruptions of immunity, antioxidant system, apoptosis regulation, and metabolism upon MPs and P. lima exposure were illustrated by gene expression and comparative metabolomic analyses. Furthermore, the mussels that experienced MP-exposure were shown to be more vulnerable to P. lima, indicated by greater degree of deleterious effects on abovementioned parameters detected. In general, our findings emphasize the threat of MPs and HABs to bivalve species, which deserves close attention and more investigation.

Prevalence and Determinants of Anxiety and Depression Among Healthcare Workers in Liaoning Province, China.

Purpose: To assess the anxiety and depression and their predictors among healthcare workers in Liaoning Province, China. Methods: In order to explore the influencing factors and prevalence of anxiety and depression among healthcare workers, a cross-sectional research design was used to survey 500 healthcare workers using the 14-item Hospital Anxiety Depression Scale (HADS), the Rosenberg Self-Esteem Scale (RSES), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Survey of Perceived Organizational Support (SPOS). Results: About 47.12% of the healthcare workers suffered from anxiety and 71.63% suffered from depression. In our study, we found that the health status (OR: 0.540, 95% CI: 0.298-0.976), self-esteem (OR: 0.395, 95% CI: 0.251-0.619), PSS (OR: 0.621, 95% CI: 0.388-0.994), organizational support (OR: 0.533, 95% CI. 0.333-0.854) were protective factors for healthcare workers suffering from anxiety, and resistance to COVID-19 (OR: 1.703, 95% CI: 1.082-2.681) was a risk factor for healthcare workers suffering from anxiety, while good quality of life (OR: 0.385, 95% CI: 0.206-0.719) self-esteem (OR: 0.187, 95% CI: 0.110-0.317), and PSS (OR: 0.475, 95% CI: 0.267-0.847) were protective factors for healthcare workers suffering from depression, and at the age of 35-40 years (OR: 2.475, 95% CI: 1.140-5.369) and resistance to COVID-19 (OR: 2.219, 95% CI: 1.313-3.751) were risk factors for healthcare workers suffering from depression. Conclusion: The anxiety and depression status of healthcare workers in China is poor, and hospital administrators should take positive measures to support healthcare workers and give positive expectations to alleviate negative emotions such as anxiety and depression.

Enrofloxacin exposure undermines gut health and disrupts neurotransmitters along the microbiota-gut-brain axis in zebrafish.

The environmental prevalence of antibiotic residues poses a potential threat to gut health and may thereby disrupt brain function through the microbiota-gut-brain axis. However, little is currently known about the impacts of antibiotics on gut health and neurotransmitters along the microbiota-gut-brain axis in fish species. Taking enrofloxacin (ENR) as a representative, the impacts of antibiotic exposure on the gut structural integrity, intestinal microenvironment, and neurotransmitters along the microbiota-gut-brain axis were evaluated in zebrafish in this study. Data obtained demonstrated that exposure of zebrafish to 28-day environmentally realistic levels of ENR (6 and 60 µg/L) generally resulted in marked elevation of two intestinal integrity biomarkers (diamine oxidase (DAO) and malondialdehyde (MDA), upregulation of genes that encode inter-epithelial tight junction proteins, and histological alterations in gut as well as increase of lipopolysaccharide (LPS) in plasma, indicating an evident impairment of the structural integrity of gut. Moreover, in addition to significantly altered neurotransmitters, markedly higher levels of LPS while less amount of two short-chain fatty acids (SCFAs), namely acetic acid and valeric acid, were detected in the gut of ENR-exposed zebrafish, suggesting a disruption of gut microenvironment upon ENR exposure. Along with corresponding changes detected in gut, significant disruption of neurotransmitters in brain indicated by marked alterations in the contents of neurotransmitters, the activity of acetylcholin esterase (AChE), and the expression of neurotransmitter-related genes were also observed. These findings suggest exposure to environmental antibiotic residues may impair gut health and disrupt neurotransmitters along the microbiota-gut-brain axis in zebrafish. Considering the prevalence of antibiotic residues in environments and the high homology of zebrafish to other vertebrates including human, the risk of antibiotic exposure to the health of wild animals as well as human deserves more attention.

Psychometric Characteristics of the Chinese Version of the Tuberculosis Related-Stigma Scale in a Population of Medical Students and Its Correlation with Selected Demographic Characteristics.

Background: As future health workers, medical students' attitudes towards tuberculosis (TB) patients can impact TB control. However, in China, there is a lack of well-quantified assessment regarding the stigma among medical students towards TB patients. Therefore, this study aimed to validate the Chinese version of the Tuberculosis related-Stigma Scale (TSS) in medical students and to apply the scale to measure stigma and its determinants. Methods: A total of 1035 eligible medical students participated in the cross-sectional questionnaire. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were first conducted to test Chinese version of the TSS construct validity, and then internal consistency was assessed using Cronbach's α. Finally, multiple linear regression analyses were conducted to identify predictors of stigma. Results: EFA extracted two factors ("Social distance" and "Exclusionary sentiments"). The CFA further confirmed the two-factor construct. The internal consistency, convergent and divergent validity of the adapted Chinese version of the TSS was acceptable. Furthermore, Whether one has received TB health education and whether know a person with TB are associated with all dimensions of TB stigma, while differences in sex and place of residence play different roles in influencing the different dimensions of stigma. Conclusion: The adapted Chinese version of the TSS can be used to assess the level of stigma among medical students in China towards tuberculosis patients. When implementing future interventions to reduce stigma associated with TB, special attention should be given to medical students from urban areas, of male gender, who have not received TB health education, and no know a person with TB. However, these two dimensions ("Social distance" and "Exclusionary sentiments") are impacted by different determinants and should therefore be addressed separately when designing, implementing, and evaluating measures to reduce stigma.

Determination of Tumor Marker Screening for Lung Cancer Using ROC Curves.

Introduction: Lung cancer ranks first among malignant tumors worldwide and is a leading cause of cancer-related mortality in both men and women. Combining tumor marker testing is a strategy to screen individuals at high risk of pulmonary cancer and minimize pulmonary cancer mortality. Therefore, tumor marker screening is crucial. In this study, we analyzed combinations of tumor markers for lung cancer screening using receiver operating characteristic (ROC) curve analysis. Methods: A retrospective descriptive study was conducted on patients diagnosed with lung cancer, as well as healthy and benign lung diseases, using data from the China Huludao Central Hospital database between January 2016 and July 2022. The t-test and ROC curve were utilized to assess the effectiveness of individual tumor marker and the combination of multiple tumor markers. Tumor markers are molecular products metabolized and secreted by tumor tissues, characterized by cells or body fluids. They serve as indicators of tumor stage and grading, monitor treatment response, and predict recurrence. Results: In this study, 267 healthy participants, 385 patients with benign lesions, and 296 patients with lung cancer underwent tumor marker screening. The sensitivity of five tumor markers-CEA, CYFRA21-1, NSE, pro-GRP, and CA125-was found to be <55%. This study revealed that a single tumor marker had limited value in lung cancer screening. However, combining two or more markers yielded varying area under the curves (AUC), with no significant impact on screening accuracy. The combination of CEA + CA125 demonstrated the highest accuracy for lung cancer screening in healthy participants. At a cutoff of 0.447 for CEA + CA125, the combination showed a sensitivity of 0.676 and specificity of 0.846 for lung cancer screening. Conversely, for patients with benign lung lesions, the optimal combination was CEA + NSE, with a cutoff of 0.393, yielding a sensitivity of 0.645 and specificity of 0.766 for lung cancer screening. Conclusion: The five tumor markers-CEA, CA125, CY211, NSE, GRP-show promising results in screening healthy individuals and patients with lung cancer. However, only CEA, NSE, and GRP effectively differentiate patients with benign lung lesions from those with lung cancer. A single tumor marker has limited utility in detecting and screening for lung cancer and should be combined with other tumor markers. CEA + CA125 emerges as a superior tumor marker for distinguishing healthy individuals from those with lung cancer, whereas the CEA + NSE combination is more effective in identifying tumor markers in patients with benign lung lesions and lung cancer.

Recent developments in the fabrication of food microparticles and nanoparticles using microfluidic systems.

Microfluidics is revolutionizing the production of microparticles and nanoparticles, offering precise control over dimensions and internal structure. This technology facilitates the creation of colloidal delivery systems capable of encapsulating and releasing nutraceuticals. Nutraceuticals, often derived from food-grade ingredients, can be used for developing functional foods. This review focuses on the principles and applications of microfluidic systems in crafting colloidal delivery systems for nutraceuticals. It explores the foundational principles behind the development of microfluidic devices for nutraceutical encapsulation and delivery. Additionally, it examines the prospects and challenges with using microfluidics for functional food development. Microfluidic systems can be employed to form emulsions, liposomes, microgels and microspheres, by manipulating minute volumes of fluids flowing within microchannels. This versatility can enhance the dispersibility, stability, and bioavailability of nutraceuticals. However, challenges as scaling up production, fabrication complexity, and microchannel clogging hinder the widespread application of microfluidic technologies. In conclusion, this review highlights the potential role of microfluidics in design and fabrication of nutraceutical delivery systems. At present, this technology is most suitable for exploring the role of specific delivery system features (such as particle size, composition and morphology) on the stability and bioavailability of nutraceuticals, rather than for large-scale production of nutraceutical delivery systems.

Reciprocal communication between FAPs and muscle cells via distinct extracellular vesicle miRNAs in muscle regeneration.

Muscle regeneration is a complex process relying on precise teamwork between multiple cell types, including muscle stem cells (MuSCs) and fibroadipogenic progenitors (FAPs). FAPs are also the main source of intramuscular adipose tissue (IMAT). Muscles without FAPs exhibit decreased IMAT infiltration but also deficient muscle regeneration, indicating the importance of FAPs in the repair process. Here, we demonstrate the presence of bidirectional crosstalk between FAPs and MuSCs via their secretion of extracellular vesicles (EVs) containing distinct clusters of miRNAs that is crucial for normal muscle regeneration. Thus, after acute muscle injury, there is activation of FAPs leading to a transient rise in IMAT. These FAPs also release EVs enriched with a selected group of miRNAs, a number of which come from an imprinted region on chromosome 12. The most abundant of these is miR-127-3p, which targets the sphingosine-1-phosphate receptor S1pr3 and activates myogenesis. Indeed, intramuscular injection of EVs from immortalized FAPs speeds regeneration of injured muscle. In late stages of muscle repair, in a feedback loop, MuSCs and their derived myoblasts/myotubes secrete EVs enriched in miR-206-3p and miR-27a/b-3p. The miRNAs repress FAP adipogenesis, allowing full muscle regeneration. Together, the reciprocal communication between FAPs and muscle cells via miRNAs in their secreted EVs plays a critical role in limiting IMAT infiltration while stimulating muscle regeneration, hence providing an important mechanism for skeletal muscle repair and homeostasis.

Juglone induces ferroptosis in glioblastoma cells by inhibiting the Nrf2-GPX4 axis through the phosphorylation of p38MAPK.

BACKGROUND: Ferroptosis, a non-apoptotic form of cell death induced by accumulation of free iron ions and lipid peroxidation, its importance for cancer treatment is gradually being recognized. Research on the anti-cancer mechanism of juglone is accumulating. However, the specific mechanism by which it directs glioblastoma (GBM) to death is unknown. METHODS: We used in vitro and in vivo experiments to explore the anti-GBM effect generated by juglone through the ferroptosis pathway. RESULTS: Juglone mainly causes cell death by inducing ferroptosis. Mechanistically, juglone can significantly activate the phosphorylation of p38MAPK. According to transcriptome sequencing and protein interaction analysis, the Nrf2-GPX4 signaling pathway is identified as the primary pathway through which juglone mediates ferroptosis. In vitro and in vivo experiments further verified that juglone induces the ferroptosis of GBM by activating the phosphorylation of p38MAPK and negatively regulating the Nrf2-GPX4 signaling pathway. CONCLUSION: Juglone induces ferroptosis and inhibits the growth of GBM by targeting the Nrf2/Gpx4 signaling pathway and thus holds promise as a novel ferroptosis inducer or anti-GBM drug.

High-Throughput Host-Microbe Single-Cell RNA Sequencing Reveals Ferroptosis-Associated Heterogeneity during Acinetobacter baumannii Infection.

Interactions between host and bacterial cells are integral to human physiology. The complexity of host-microbe interactions extends to different cell types, spatial aspects, and phenotypic heterogeneity, requiring high-resolution approaches to capture their full complexity. The latest breakthroughs in single-cell RNA sequencing (scRNA-seq) have opened up a new era of studies in host-pathogen interactions. Here, we first report a high-throughput cross-species dual scRNA-seq technology by using random primers to simultaneously capture both eukaryotic and bacterial RNAs (scRandom-seq). Using reference cells, scRandom-seq can detect individual eukaryotic and bacterial cells with high throughput and high specificity. Acinetobacter baumannii (A.b) is a highly opportunistic and nosocomial pathogen that displays resistance to many antibiotics, posing a significant threat to human health, calling for discoveries and treatment. In the A.b infection model, scRandom-seq witnessed polarization of THP-1 derived-macrophages and the intracellular A.b-induced ferroptosis-stress in host cells. The inhibition of ferroptosis by Ferrostatin-1 (Fer-1) resulted in the improvement of cell vitality and resistance to A.b infection, indicating the potential to resist related infections. scRandom-seq provides a high-throughput cross-species dual single-cell RNA profiling tool that will facilitate future discoveries in unraveling the complex interactions of host-microbe interactions in infection systems and tumor micro-environments.

Microplastics weaken the exoskeletal mechanical properties of Pacific whiteleg shrimp Litopenaeus vannamei.

The ubiquitous presence of microplastics (MPs) in aquatic environments poses a significant threat to crustaceans. Although exoskeleton quality is critical for crustacean survival, the impact of MPs on crustacean exoskeletons remains elusive. Our study represents a pioneering effort to characterize the effects of MPs exposure on crustacean exoskeletons. In this study, the mechanical properties of whiteleg shrimp Litopenaeus vannamei exoskeletons were analyzed after exposure to environmentally realistic levels of MPs. Nanoindentation data demonstrated that MPs exposure significantly increased the hardness and modulus of both the carapace and abdominal segments of L. vannamei. Moreover, fractures and embedded MPs were detected on the exoskeleton surface using SEM-EDS analysis. Further analysis demonstrated that the degree of chitin acetylation (DA) in the shrimp exoskeleton, as indicated by FTIR peaks, was reduced by MPs exposure. In addition, exposure to MPs significantly inhibited the muscle Ca2+-ATPase activity and hemolymph calcium levels. Transcriptome and metabolome analyses revealed that the expression levels of genes encoding key enzymes and metabolites in the chitin biosynthetic pathway were significantly affected by MPs exposure. In conclusion, MPs at environmentally relevant concentrations may affect the exoskeletal mechanical properties of L. vannamei through a comprehensive mechanism involving the disruption of the crystalline structure of chitin, assimilation into the exoskeleton, and dysregulation of exoskeleton biosynthesis-related pathways.

Association between Perfluoroalkyl Substances in Follicular Fluid and Polycystic Ovary Syndrome in Infertile Women.

In recent years, perfluoroalkyl substances (PFASs), a family of fluorinated organic com pounds, have garnered much attention due to their reproductive and developmental toxicity in humans. Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease that affects women of reproductive age and is a significant contributor to female infertility. A previous study suggested that PFASs play a possible role in PCOS. We conducted a clinical study investigating the relationship between PCOS and PFAS in follicular fluid. A total of 73 infertile patients with PCOS and 218 controls were recruited from the International Peace Maternity and Child Health Hospital, affiliated with the Shanghai Jiao Tong University School of Medicine. The concentrations of 12 PFASs in follicular fluid samples and sex hormones in serum were measured. Correlation analysis and multiple linear regression revealed a positive relationship between perfluorooctanoic acid (PFOA) and testosterone (T) concentrations. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each PFAS were estimated using multivariable logistic regression and quantile-based g-computation (QGC). The PFOA concentrations in follicular fluid were correlated with increased odds of PCOS (second vs. first quartile: OR = 3.65, 95% CI: 1.47-9.05, p = 0.005; third vs. first quartile: OR = 2.91, 95% CI: 1.17-7.26, p = 0.022; fourth vs. first quartile: OR = 3.13, 95% CI: 1.21-8.09, p = 0.019; P for trend = 0.032). This association was confirmed with QGC. Mediation analysis suggested that the mediation effect of T in association with PFOA and PCOS was not statistically significant. Our study suggests that PFOA may be a risk factor for PCOS.

Activation of Intestinal HIF2α Ameliorates Iron-Refractory Anemia.

In clinics, hepcidin levels are elevated in various anemia-related conditions, particularly in iron-refractory anemia and in high inflammatory states that suppress iron absorption, which remains an urgent unmet medical need. To identify effective treatment options for various types of iron-refractory anemia, the potential effect of hypoxia and pharmacologically-mimetic drug FG-4592 (Roxadustat) are evaluated, a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitor, on mouse models of iron-refractory iron-deficiency anemia (IRIDA), anemia of inflammation and 5-fluorouracil-induced chemotherapy-related anemia. The potent protective effects of both hypoxia and FG-4592 on IRIDA as well as other 2 tested mouse cohorts are found. Mechanistically, it is demonstrated that hypoxia or FG-4592 could stabilize duodenal Hif2α, leading to the activation of Fpn transcription regardless of hepcidin levels, which in turn results in increased intestinal iron absorption and the amelioration of hepcidin-activated anemias. Moreover, duodenal Hif2α overexpression fully rescues phenotypes of Tmprss6 knockout mice, and Hif2α knockout in the gut significantly delays the recovery from 5-fluorouracil-induced anemia, which can not be rescued by FG-4592 treatment. Taken together, the findings of this study provide compelling evidence that targeting intestinal hypoxia-related pathways can serve as a potential therapeutic strategy for treating a broad spectrum of anemia, especially iron refractory anemia.

Global burden of leukemia attributable to occupational exposure to formaldehyde from 1990 to 2019.

The objective of this study was to evaluate the worldwide burden of leukemia owing to occupational exposure to formaldehyde (OEF) from 1990 to 2019. Data on leukemia due to OEF were obtained from the Global Burden of Disease Study (GBD) 2019. By region, age, sex, and disease subtype, the numbers and age-standardized rates (ASRs) associated with deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) were analyzed. Annual average percentage change (AAPC) was used to estimate disease burden trends from 1990 to 2019. To measure the risk of leukemia due to OEF, the population attributable fraction (PAF) was introduced. From 1990 to 2019, the number of deaths, DALYs, YLLs, and YLDs for leukemia caused by OEF increased by 44%, 34%, 33%, and 124%, respectively. Regarding the change in ASRs, the age-standardized YLDs (ASYLDs) rate of leukemia due to OEF, which was 38.03% (AAPC = 1.17 [95% confidence interval [CI] 1.11, 1.23]), indicated an increased trend. But the age-standardized mortality rate (ASMR), age-standardized DALY (ASDALY) rate, and age-standardized YLL (ASYLL) rate showed decline trends, with - 11.90% (AAPC = - 0.41 [95% CI - 0.45, - 0.37]), - 14.19% (AAPC = - 0.5 [95% CI - 0.55, - 0.45]), and - 14.97% (AAPC = - 0.53 [95% CI - 0.58, - 0.48]), respectively. In terms of PAFs, there were increasing trends in PAFs of age-standardized deaths, ASDALYs, ASYLLs, and ASYLDs for leukemia caused by OEF, with 20.15% (95% uncertainty interval [UI] 11.76%, 30.25%), 36.28% (95% UI 21.46%, 53.42%), 51.91% (95% UI 35.05%, 72.07%), and 36.34% (95% UI 21.58%, 53.63%), respectively. Across the socio-demographic index (SDI) regions, the leukemia burden caused by OEF was concentrated in middle and high-middle SDI regions. Besides, OEF poses a more serious risk for acute leukemia among the leukemia subtype. Globally, leukemia caused by OEF remains a public health burden. Policies must be developed to avoid the burden of leukemia caused by OEF.

A Transformable Supramolecular Bispecific Cell Engager for Augmenting Natural Killer and T Cell-Based Cancer Immunotherapy.

Immune cells are pivotal in cancer immunotherapy, yet their therapeutic effectiveness is often hampered by limited tumor infiltration and inhibitory tumor microenvironments. An alkaline phosphatase (ALP)-responsive and transformable supramolecular bis-specific cell engager (Supra-BiCE) to harness natural killer (NK)/T cells for effective cancer immunotherapy is introduced here. The Supra-BiCE, consisting of both SA-P (a phosphorylated peptide targeting and blocking programmed cell death ligand 1 (PD-L1)) and SA-T (a phosphorylated peptide targeting and blocking T cell immunoglobulin and ITIM domain (TIGIT)) is constructed by a simple co-assembling strategy. Upon intravenous administration, Supra-BiCE self-assembles into nanoribbons and interacts with NK/T cells via TIGIT. Notably, these nanoribbons undergo transformation into long nanofibrils within ALP-overexpressing tumor regions, resulting in enhanced binding affinities of Supra-BiCE to both PD-L1 and TIGIT. Consequently, this leads to the accumulation and retention of NK/T cells within tumor regions. Furthermore, the combinatorial blockade of checkpoints by Supra-BiCE activates infiltrating NK/T cells. Moreover, the adjustable peptide ratio in Supra-BiCE enables customization for optimal therapeutic effects against distinct tumor types. Particularly, Supra-BiCE (T:P = 1:3) achieved 98.27% tumor suppression rate against colon carcinoma model. Overall, this study offers a promising tool for engaging NK and T cells for cancer immunotherapy.

Light-Triggered Signal Enhancement Strategy Integrated with a CRISPR/Cas13a-Based Assay for Ultrasensitive and Specific miRNA Detection.

The development of facile, accurate, and affordable assays for microRNAs (miRNAs) in early cancer is greatly desirable but encounters an obstacle due to low cellular abundance in biofuids. In this study, we present a novel approach called a light-triggered exponential amplification strategy coupled with a CRISPR/Cas13a-based diagnostic system (LEXPA-CRISPR), which directly transduces rare miRNA targets into photocontrolled signal enhancement response. This innovative platform leverages trans-cleavage of CRISPR/Cas13a, activated by the miRNA target, to cleave specific RNA fragments within the MB@PC-NAC assembly, thus releasing free PC-single-stranded DNA (PC-ssDNA) that is modified by a photocleavable linker (PC linker). UV irradiation is further employed toward the photoresponsive PC-ssDNA, resulting in instantaneous generation of oligo with a new 5' phosphate group (Pho-ssDNA). The Pho-ssDNA serves as a trigger for rolling circle amplification (RCA) reaction, which generates thousands of long ssDNA repeats of diverse lengths with a strong fluorescence signal. Through optimization, we achieved a detection limit of 1 fM for miR21 without the need for target amplification. Moreover, the programmable versatility of LEXPA-CRISPR is also demonstrated for miR17 determination only with simple modification of CRISPR RNA (crRNA) sequences. This proposed biosensor successfully monitored the levels of miR21 and miR17 in tumor cells, showing a satisfactory consistency with the standard qRT-PCR method. Conclusively, LEXPA-CRISPR represents a promising strategy for ultrasensitive miRNA detection. It combines the advantages of light-triggered signal amplification and robust collateral cleavage activity of Cas13a, making it an attractive tool for practical CRISPR-based diagnostics.