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Objective Alzheimer’s disease (AD) and other dementias are major public health concerns with an increasing global impact. The burden of these conditions varies by region, age, and gender, and the COVID-19 pandemic has further exacerbated these disparities, potentially influencing disease prevalence, mortality, and disability burden. This study aimed to assess the global and regional burden and trends of Alzheimer’s disease and other dementias in adults aged 60 years or older from 1990 to 2021, with a particular focus on the impact of the COVID-19 pandemic on mortality, prevalence, and disability-adjusted life years. Methods Using Global Burden of Disease (GBD 2021) data, we analyzed age-standardized death rates (ASDR), incidence rates (ASIR), prevalence rates (ASPR), and disability-adjusted life years (DALYs) from 1990 to 2021. Temporal trends were assessed using the Estimated Annual Percentage Change (EAPC). Projections were modeled using Bayesian Age-Period-Cohort (BAPC) techniques. We evaluated excess mortality by comparing actual versus expected deaths during the pandemic. Decomposition analysis examined the contributions of population growth, aging, and epidemiological shifts. We analyzed health inequality to highlight and address disparities in health status and resource access across regions. All plots and tables were created using Joinpoint Regression model (Version 4.8.0.1), StataMP 18, and R statistical packages (Version 4.4.1). Results In 2021, global mortality from AD and other dementias among individuals aged 60 and older reached approximately 1,922,970.75 cases (95% CI: 480,348.08 to 5,104,315.95), and the prevalence was 52,560,253.51 cases (95% CI: 41,399,948.84 to 65,633,448.71). High Body Mass Index (BMI) and High Fasting Plasma Glucose (FPG) were prominent risk factors. Projections suggest a near fourfold increase in AD cases by 2050, driven by population growth and aging, with females disproportionately affected. Health inequalities persist, with higher disease burdens in high-SDI regions. The pandemic impacted mortality unevenly, highlighting regional disparities. Conclusion Although incidence rates declined from 1990 to 2021, the overall burden of AD and dementias remains substantial and is expected to rise significantly by 2050. The findings underscore the need for targeted interventions addressing risk factors like High FPG, gender disparities, and the socioeconomic effects of COVID-19, particularly in high-SDI countries.

The efficacy of checkpoint immunotherapy to non-small cell lung cancer (NSCLC) largely depends on the tumor microenvironment (TME). Here, we demonstrate that CCL7 facilitates anti-PD-1 therapy for the Kras LSL−G12D/+ Tp53 fl/fl (KP) and the Kras LSL−G12D/+ Lkb1 fl/fl (KL) NSCLC mouse models by recruiting conventional DC 1 (cDC1) into the TME to promote T cell expansion. CCL7 exhibits high expression in NSCLC tumor tissues and is positively correlated with the infiltration of cDC1 in the TME and the overall survival of NSCLC patients. CCL7 deficiency impairs the infiltration of cDC1 in the TME and the subsequent expansion of CD8 + and CD4 + T cells in bronchial draining lymph nodes and TME, thereby promoting tumor development in the KP mouse model. Administration of CCL7 into lungs alone or in combination with anti-PD-1 significantly inhibits tumor development and prolongs the survival of KP and KL mice. These findings suggest that CCL7 potentially serves as a biomarker and adjuvant for checkpoint immunotherapy of NSCLC. Only a limited proportion of patients with non-small cell lung cancer respond to anti-PD-1/PD-L1 immunotherapy. Here, the authors show that in autochthonous models of KRAS-mutated lung cancer, CCL7 promotes cDC1 infiltration into the lungs, sustaining antitumor immune responses and potentiating anti-PD1 treatment efficacy.

Macrophages are plastic and, in response to different local stimuli, can polarize toward multi-dimensional spectrum of phenotypes, including the pro-inflammatory M1-like and the anti-inflammatory M2-like states. Using a high-throughput phenotypic screen in a library of ~4000 FDA-approved drugs, bioactive compounds and natural products, we find ~300 compounds that potently activate primary human macrophages toward either M1-like or M2-like state, of which ~30 are capable of reprogramming M1-like macrophages toward M2-like state and another ~20 for the reverse repolarization. Transcriptional analyses of macrophages treated with 34 non-redundant compounds identify both shared and unique targets and pathways through which the tested compounds modulate macrophage activation. One M1-activating compound, thiostrepton, is able to reprogram tumor-associated macrophages toward M1-like state in mice, and exhibit potent anti-tumor activity. Our compound-screening results thus help to provide a valuable resource not only for studying the macrophage biology but also for developing therapeutics through modulating macrophage activation. Macrophages may polarize into different states with distinct regulatory functions for inflammation. Here the authors perform high-throughput in vitro screening of a library of ~4000 compounds to identify those with specific effects on human macrophage polarization, while RNAseq helps uncover the targets and pathways mediating these effects.

Background Sleep and physical activity (PA) are thought to be interconnected with the development of rheumatoid arthritis (RA). However, the precise nature and extent of these relationships have yet to be fully quantified. This study aimed to quantify the longitudinal effects of sleep behaviors, PA, and genetic susceptibility on the incidence of RA and to estimate the combined effects and interactions among these exposures. Methods A total of 363,211 adults were derived from a large European cohort. We incorporated five sleep behaviors (sleep duration, insomnia, snoring, chronotype, and daytime sleepiness) to generate sleep patterns, which were defined based on healthy sleep scores. Multivariate-adjusted Cox proportional hazard models were conducted to assess the individual and combined associations of sleep patterns, PA, and genetic susceptibility with the risk of RA occurrence. Multiplicative and additive interactions were estimated by P interaction and relative excess risk due to interaction (RERI) between each of the two exposures. Results During a follow-up of 12.5 years, 4262 RA cases were ascertained. A healthy sleep pattern was associated with a decreased risk of RA in a dose-response manner, with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI] = 0.75–0.84), independent of traditional risk factors and genetic predisposition. Under the restricted cubic splines model, a non-linear association was detected for PA and RA risk. Participants in the intermediate quintile 3 showed the lowest risk for developing RA, with a HR 95% CI of 0.84 (0.76–0.92). Moreover, there was an additive interaction effect of intermediate sleep pattern and PA, with a 0.45 (95% CI = 0.02–0.87) RERI of developing RA. Additionally, individuals at high genetic risk had the greatest 10-year absolute risk reduction (10.58 per 1000 person-years) when adopting both favorable behaviors. Conclusions A healthy sleep pattern and moderate PA were associated with a reduced risk of developing RA, which can offset the deleterious effects of predisposing genetic components. Implementing these modifiable lifestyle factors into public health practices is beneficial for RA prevention.

Cation channel of sperm 1 (CATSPER1) is a unique sperm cation channel protein, and essential for sperm function and male fertility. CATSPER1 exclusively expresses in meiotic and postmeiotic spermatogenic cells, thus belongs to the spermatogenesis-specific antigen that escape central tolerance. We have previously demonstrated the immunocontraceptive potential of its transmembrane domains and pore region, and reported the antifertility effects of its B-cell epitopes on male mice. Aiming to develop DNA vaccine targeting CATSPER1 for male contraception, here the whole open reading frame of mouse Catsper1 was cloned into the plasmid pEGFP-N1 to obtain a DNA vaccine pEGFP-N1-Catsper1. The vaccine was confirmed to be transcribed and translated in mouse N2a cell in vitro and mouse muscle tissue in vivo. Intramuscular injection with the vaccine on male mice induced specific immune reaction and caused significant inhibition on sperm hyperactivated motility and progressive motility (P<0.001 for both), and consequently reduced male fertility. The fertility rate of experimental group was 40.9%, which was significant lower (P=0.012) than control group (81.8%). No significant change in mating behavior, sperm production and histology of testis/epididymis was observed. Given that Catsper1 exhibits a high degree of homology among different species, Catsper1 DNA vaccine might be a good strategy for developing an immunocontraceptive vaccine for human and animal use.

This paper is aimed at exploring the implications of velocity-dispersion scalings on high-mass star formation in molecular clouds, including the scalings of Larson’s linewidth–size (σ– R) and ratio–mass surface density ( L – Σ; here L = σ/R 0.5). We have systematically analyzed the σ parameter of well-selected 221 massive clumps, complemented with published samples of other hierarchical density structures of molecular clouds over spatial scales of 0.01–10 pc. Those massive clumps are classified into four phases: quiescent, protostellar, H ii region, and PDR clumps in an evolutionary sequence. The velocity dispersion of clumps increases overall with the evolutionary sequence, reflecting enhanced stellar feedback in more evolved phases. The relations of σ– R and L – Σ are weak with the clump sample alone, but become evident when combined with others spanning a much wider spatial scales. For σ– R, its tight relation indicates a kinematic connection between hierarchical density structures, supporting theoretical models of multiscale high-mass star formation. From the L – Σ relation, cloud structures can be found to transition from overvirial state (α vir > 2) to subvirial state (α vir < 2) as they become smaller and denser, indicating a possible shift in the governing force from turbulence to gravity. This implies that the multiscale physical process of high-mass star formation hinges on the self-gravity of subvirial molecular clouds. However, the influence of turbulence may not be dismissed until large-scale clouds attain a subvirial state. This is pending confirmation from future multiscale kinematic observations of molecular clouds with uniform observing settings.

Background The sorghum aphid Melanaphis sacchari (Zehntner) (Homoptera: Aphididae) is an important insect in the late growth phase of sorghum ( Sorghum bicolor L.). However, the mechanisms of sorghum response to aphid infestation are unclear. Results In this paper, the mechanisms of aphid resistance in different types of sorghum varieties were revealed by studying the epidermal cell structure and performing a transcriptome and metabolome association analysis of aphid-resistant and aphid-susceptible varieties. The epidermal cell results showed that the resistance of sorghum to aphids was positively correlated with epidermal cell regularity and negatively correlated with the intercellular space and leaf thickness. Transcriptome and metabolomic analyses showed that differentially expressed genes in the resistant variety HN16 and susceptible variety BTX623 were mainly enriched in the flavonoid biosynthesis pathway and differentially expressed metabolites were mainly related to isoflavonoid biosynthesis and flavonoid biosynthesis. The q-PCR results of key genes were consistent with the transcriptome expression results. Meanwhile, the metabolome test results showed that after aphidinfestation, naringenin and genistein were significantly upregulated in the aphid-resistant variety HN16 and aphid-susceptible variety BTX623 while luteolin was only significantly upregulated in BTX623. These results show that naringenin, genistein, and luteolin play important roles in plant resistance to aphid infestation. The results of exogenous spraying tests showed that a 1‰ concentration of naringenin and genistein is optimal for improving sorghum resistance to aphid feeding. Conclusions In summary, the physical properties of the sorghum leaf structure related to aphid resistance were studied to provide a reference for the breeding of aphid-resistant varieties. The flavonoid biosynthesis pathway plays an important role in the response of sorghum aphids and represents an important basis for the biological control of these pests. The results of the spraying experiment provide insights for developing anti-aphid substances in the future.

Phototherapy, encompassing the utilization of both natural and artificial light, has emerged as a dependable and non-invasive strategy for addressing a diverse range of illnesses, diseases, and infections. This therapeutic approach, primarily known for its efficacy in treating skin infections, such as herpes and acne lesions, involves the synergistic use of specific light wavelengths and photosensitizers, like methylene blue. Photodynamic therapy, as it is termed, relies on the generation of antimicrobial reactive oxygen species (ROS) through the interaction between light and externally applied photosensitizers. Recent research, however, has highlighted the intrinsic antimicrobial properties of light itself, marking a paradigm shift in focus from exogenous agents to the inherent photosensitivity of molecules found naturally within pathogens. Chemical analyses have identified specific organic molecular structures and systems, including protoporphyrins and conjugated C=C bonds, as pivotal components in molecular photosensitivity. Given the prevalence of these systems in organic life forms, there is an urgent need to investigate the potential impact of phototherapy on individual molecules expressed within pathogens and discern their contributions to the antimicrobial effects of light. This review delves into the recently unveiled key molecular targets of phototherapy, offering insights into their potential downstream implications and therapeutic applications. By shedding light on these fundamental molecular mechanisms, we aim to advance our understanding of phototherapy’s broader therapeutic potential and contribute to the development of innovative treatments for a wide array of microbial infections and diseases.

Rapid antimicrobial susceptibility testing (AST) is urgently needed for treating infections with appropriate antibiotics and slowing down the emergence of antibiotic‐resistant bacteria. Here, a phenotypic platform that rapidly produces AST results by femtosecond stimulated Raman scattering imaging of deuterium oxide (D2O) metabolism is reported. Metabolic incorporation of D2O into biomass in a single bacterium and the metabolic response to antibiotics are probed in as short as 10 min after culture in 70% D2O medium, the fastest among current technologies. Single‐cell metabolism inactivation concentration (SC‐MIC) is obtained in less than 2.5 h from colony to results. The SC‐MIC results of 37 sets of bacterial isolate samples, which include 8 major bacterial species and 14 different antibiotics often encountered in clinic, are validated by standard minimal inhibitory concentration blindly measured via broth microdilution. Toward clinical translation, stimulated Raman scattering imaging of D2O metabolic incorporation and SC‐MIC determination after 1 h antibiotic treatment and 30 min mixture of D2O and antibiotics incubation of bacteria in urine or whole blood is demonstrated. A phenotypic platform that rapidly produces antimicrobial susceptibility testing results by femtosecond stimulated Raman scattering imaging of D2O metabolism is reported. Metabolic incorporation of D2O into biomass in a single bacterium and the metabolic response to antibiotics are probed. Single‐cell metabolism inactivation concentration is obtained in less than 2.5 h from colony to results.

In recent years, there have been frequent cases of impact on the stable development of supply chain economy caused by uncertain events such as COVID-19 and extreme weather events. The creation, management, and impact coping techniques of the supply chain economy now face wholly novel requirements as a result of the escalating level of global uncertainty. Although a significant literature applies uncertainty analysis and optimization modeling (UAO) to study supply chain management (SCM) under uncertainty, there is a lack of systematic literature review and research classification. Therefore, in this paper, 121 articles published in 44 international academic journals between 2015 and 2022 are extracted from the Web of Science database and reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Bibliometric analysis and CiteSpace software are used to identify current developments in the field and to summarize research characteristics and hot topics. The selected published articles are classified and analyzed by author name, year of publication, application area, country, research purposes, modeling methods, research gaps and contributions, research results, and journals to comprehensively review and evaluate the SCM in the application of UAO. We find that UAO is widely used in SCM under uncertainty, especially in the field of decision-making, where it is common practice to abstractly model the decision problem to obtain scientific decision results. This study hopes to provide an important and valuable reference for future research on SCM under uncertainty. Future research could combine uncertainty theory with supply chain management segments (e.g., emergency management, resilience management, and security management), behavioral factors, big data technologies, artificial intelligence, etc.