The Long-term Visual Quality and Rotational Stability After ICL/TICL V4c Implantation in Individuals With High Myopia Older Than 40 Years.

PURPOSE: To investigate the long-term visual quality and rotational stability after the implantation of Implantable Collamer Lens (ICL) and toric ICL (TICL) (STAAR Surgical) in patients with myopia older than 40 years. METHODS: This study included 82 eyes of 41 patients older than 40 years with myopia who underwent ICL/TICL V4c implantation. The refraction sphere, refraction cylinder, spherical equivalent (SE), uncorrected and corrected distance visual acuity, and anterior segmental parameters were measured preoperatively and at the 1-month, 3-month, and last follow-up visits at 33 to 58 months postoperatively (mean follow-up: 42.56 ± 7.17 months). Wavefront aberrations and TICL rotation were measured using OPD-Scan III (Nidek Co Ltd) at the last follow-up visit. RESULTS: At the last follow-up visit, the overall safety and efficacy index were 1.22 ± 0.26 and 0.88 ± 0.34, respectively, without significant differences between the ICL and TICL groups. Postoperative refraction cylinder was -0.95 ± 0.64 and -0.71 ± 0.54 diopters in the ICL and TICL groups, respectively. The average vault was 467.44 ± 231.98 µm. The average TICL rotation was 5.45 ± 6.61 degrees, positively correlated with the preoperative anterior chamber volume (R2 = 0.1118, P = .026) and clockwise TICL alignment degree (R2 = 0.3110, P = .007) and negatively correlated with the 1-month vault (R2 = 0.1218, P = .008). There were no significant differences in the total, corneal, or internal aberrations and modulation transfer function AreaRatio between the ICL and TICL groups. CONCLUSIONS: Both ICL and TICL presented satisfactory long-term safety, efficacy, and visual quality in patients older than 40 years. Postoperative TICL spontaneous rotation was within the manageable range in the long term. [J Refract Surg. 2024;40(6):e381-e391.].

Key molecules regulating the blood meals of Rhipicephalus sanguineus (Acari: Ixodidae) revealed by transcriptomics.

Rhipicephalus sanguineus, a repulsive obligate blood feeder, is a three-host tick inflicting tremendous damage. Blood-sucking initiates tick-pathogen-host interactions along with alterations in the expression levels of numerous bioactive ingredients. Key molecules regulating blood meals were identified using the transcriptomic approach. A total number of 744 transcripts showed statistically significantly differential expression including 309 significantly upregulated transcripts and 435 significantly downregulated transcripts in semiengorged female ticks compared to unfed ticks, all collected in 2021. The top 10 differentially upregulated transcripts with explicit functional annotations included turripeptide OL55-like protein, valine tRNA ligase-like protein and ice-structuring glycoprotein-like protein. The top 10 differentially down-regulated transcripts were uncharacterized proteins. Gene Ontology (GO) enrichment analysis revealed four associated terms in the cellular component category and 16 in the molecular function category among the top 20 terms. Differentially expressed genes (DEGs) were enriched in GO terms ID 0000323 (lytic vacuole) and ID 0005773 (vacuole). The top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included metabolism, cellular processes, organismal systems and human diseases. The DEGs were enriched in the KEGG term ID: ko-04142 (lysosome pathway) associated with intracellular digestion in the tick midgut epithelium. Molecular markers annotated via comparative transcriptomic profiling were expected to be candidate markers for the purpose of tick control.

Synergistic dual cell therapy for atherosclerosis regression: ROS-responsive Bio-liposomes co-loaded with Geniposide and Emodin.

The development of nanomaterials for delivering natural compounds has emerged as a promising approach for atherosclerosis therapy. However, premature drug release remains a challenge. Here, we present a ROS-responsive biomimetic nanocomplex co-loaded with Geniposide (GP) and Emodin (EM) in nanoliposome particles (LP NPs) for targeted atherosclerosis therapy. The nanocomplex, hybridized with the macrophage membrane (Møm), effectively evades immune system clearance and targets atherosclerotic plaques. A modified thioketal (TK) system responds to ROS-rich plaque regions, triggering controlled drug release. In vitro, the nanocomplex inhibits endothelial cell apoptosis and macrophage lipid accumulation, restores endothelial cell function, and promotes cholesterol effluxion. In vivo, it targets ROS-rich atherosclerotic plaques, reducing plaque area ROS levels and restoring endothelial cell function, consequently promoting cholesterol outflow. Our study demonstrates that ROS-responsive biomimetic nanocomplexes co-delivering GP and EM exert a synergistic effect against endothelial cell apoptosis and lipid deposition in macrophages, offering a promising dual-cell therapy modality for atherosclerosis regression.

A Coumarin-Based Array for the Discrimination of Amyloids.

Self-assembly of misfolded proteins can lead to the formation of amyloids, which are implicated in the onset of many pathologies including Alzheimer's disease and Parkinson's disease. The facile detection and discrimination of different amyloids are crucial for early diagnosis of amyloid-related pathologies. Here, we report the development of a fluorescent coumarin-based two-sensor array that is able to correctly discriminate between four different amyloids implicated in amyloid-related pathologies with 100% classification. The array was also applied to mouse models of Alzheimer's disease and was able to discriminate between samples from mice corresponding to early (6 months) and advanced (12 months) stages of Alzheimer's disease. Finally, the flexibility of the array was assessed by expanding the analytes to include functional amyloids. The same two-sensor array was able to correctly discriminate between eight different disease-associated and functional amyloids with 100% classification.

Research focus and thematic trends of transient receptor potential vanilloid member 1 research: a bibliometric analysis of the global publications (1990-2023).

Recently, various studies have been devoted to the study of transient receptor potential vanilloid member 1 (TRPV1)-related diseases, potential drugs, and related mechanisms. The objective of this investigation was to examine the significant areas and cutting-edge developments in TRPV1 study within recent decades. Articles or reviews were obtained from the Web of Science Core Collection. VOSviewer 1.6.18 and CiteSpace 6.1 R2 software were utilized to examine publication growth, distribution by country/region, institution, journal, authorship, references, and keywords. The software identified keywords with a high citation burstiness to determine emerging topics. From 1990 to 2023, the annual global publications increased by 62,000%, from 1 to 621. Journal of neuroscience published the most manuscripts and Nature produced the highest citations. The USA, Seoul National University and Di marzo V were the most productive and impactful institution, country, and author, respectively. "TRPV1," "Capsaicin receptor," "Activation," and "Pain" are the most important keywords. The burst keywords "TRPV1 channel," "Oxidative stress," "TRPV1 structure," and "Cancer" are supposed to be the research frontiers. The present study offers valuable insights into the understanding of TRPV1 and pain-related conditions. The research on TRPV1 has demonstrated a steady increase in studies related to pain-related diseases in the past few decades. The significance of TRPV1 in cancer pathogenesis and the resolution of its structure will emerge as a new academic trend in this field, providing direction for more widespread and comprehensive studies in the future.

Comparison of corneal and lens density measurements obtained by Pentacam and CASIA2 in myopes.

PURPOSE: To investigate the agreement between Pentacam and CASIA2 in the evaluation of corneal densities (CDs) and lens densities (LDs) in myopes. METHODS: Fifty-three patients (106 eyes) underwent comprehensive ophthalmologic examinations. CDs and LDs were measured using Pentacam and CASIA2, respectively, based on the grayscale percentage of the obtained images. Agreement between Pentacam and CASIA2 was evaluated using the consistency intraclass correlation coefficient (ICC) and represented using Bland-Altman plots. RESULTS: Compared to Pentacam, CASIA2 showed significantly higher CD and LD values in all measured zones. The ICC of the average CD and LD measured by the Pentacam and CASIA2 were 0.726 and 0.757, respectively. The ICC values of all corneal zones and lenses were above 0.7, except for the measurement of the cornea in the 0-2 mm zone (0.455), suggesting good consistency between the two devices, whose results were of different levels of linear correlation. Bland-Altman plots showed mean percentages of 3.93% for the points falling outside the limits of agreement among the densitometry results. The ICCs in different age groups were similar, but the agreement was poorer in the high myopia group (low and moderate myopia, CD: 0.739, LD: 0.753; high myopia, CD: 0.621, LD: 0.760). CONCLUSIONS: CASIA2 demonstrated good consistency with Pentacam in the measurement of CD and LD, except for measurement of CD in the central cornea and in high myopia. Despite difference in the numerical results compared with Pentacam, which made the two devices uninterchangeable, CASIA2 provides a reliable alternative densitometric measurement method.

Comparison of Clarus and Optomap Ultra-Widefield Imaging Systems before and after EVO-ICL Implantation in High Myopia.

INTRODUCTION: The aim of this study was to investigate the features of imaging differences between Clarus and Optomap ultra-widefield imaging systems after implantable collamer lens (ICL) implantation. METHODS: This was a non-randomized controlled study. Ninety-two eyes of 46 consecutive patients were enrolled. Full-scale ophthalmological examinations were conducted preoperatively. All patients underwent Clarus (CLARUS 500; Carl Zeiss, Dublin, USA) and Optomap (Daytona; Optos, UK) ultra-wide imaging sequentially under the same circumstance preoperatively and 1 month after EVO-ICL implantation. A single image was acquired from each. Dx was defined as the distance between the upper furcation of the central retinal artery and the central fovea of macula. Pixels of the optic cup and disc and Dx as well as the optic cup/disc ratio were calculated and compared on each machine before and after surgery. RESULTS: All surgeries were uneventful without complications. Safety and efficacy indices were both 100% at 1 month. Values of both optic cup and disc areas were in decrease after surgery with statistically significant differences (p < 0.001), while the cup/disc ratio remained the same (Clarus mean of differences = -0.0028, p = 0.83; Optomap mean of differences = -0.0016, p = 0.76). Dx of images captured with either machine was statistically significantly decreased (p < 0.001). Differences of both optic cup (p = 0.057) and disc (p = 0.041) areas of Clarus were more obvious than that of Optomap, while only the latter was with statistical significance. Difference of Dx of Clarus was statistically significantly larger than Optomap. CONCLUSIONS: Display ranges tend to be broadened after EVO-ICL implantation in both Clarus and Optomap ultra-widefield imaging systems, while Clarus shows a wider display range of the two, which encourages the application of Clarus when it comes to the detection of more peripheral retinal lesions.

Myopic Vascular Changes Revealed by Optical Tomography Angiography and Their Association with Myopic Fundus Manifestations.

INTRODUCTION: We aimed to quantify and evaluate fundal vascular changes at different severities of myopia using optical tomography angiography (OCTA) and explore their association with fundus changes captured by ultra-widefield (UWF) fundus cameras. METHODS: Seventy-four participants with myopia were enrolled in the study and underwent basic ophthalmic examination, OCTA, and UWF fundus photography. Multiple parameters were obtained using OCTA (flow area, structure thickness, and vessel density) and UWF fundus cameras (tessellation and parapapillary atrophy [PPA]). RESULTS: The right eye of 30 participants with low and moderate myopia and 44 participants with high myopia (HM) were included. Patients with HM had a larger flow area of the outer retina (FA-OR) and a smaller thickness of choroid (TC). Axial length was significantly correlated with retinal and choroidal flow area and thickness in the different zones. The PPA area was positively correlated with FA-OR and negatively correlated with TC. Tessellation exhibited different levels of correlation with OCTA parameters regarding the flow area, thickness, and vessel density of the fundal layers, mainly in the inner retina. CONCLUSION: FA-OR and TC exhibited sensitive changes in patients with HM and axial elongation; therefore, they could serve as predictive OCTA biomarkers. The PPA and tessellation were connected to the vascular and structural changes revealed by OCTA.

Butein, a potential drug for the treatment of bone cancer pain through bioinformatic and network pharmacology.

Bone cancer pain is a difficult-to-treat pathologic condition that impairs the patient's quality of life. The effective therapy options for BCP are restricted due to the unknown pathophysiology. Transcriptome data were obtained from the Gene Expression Omnibus database and differentially expressed gene extraction was performed. DEGs integrated with pathological targets found 68 genes in the study. Butein was discovered as a possible medication for BCP after the 68 genes were submitted to the Connectivity Map 2.0 database for drug prediction. Moreover, butein has good drug-likeness properties. To collect the butein targets, we used the CTD, SEA, TargetNet, and Super-PRED databases. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed butein's pharmacological effects, indicating that butein may aid in treating BCP by altering the hypoxia-inducible factor, NF-kappa B, angiogenesis, and sphingolipid signaling pathways. Moreover, the pathological targets integrated with drug targets were obtained as the shared gene set A, which was analyzed by ClueGO and MCODE. Biological process analysis and MCODE algorithm further analyzed that BCP related targets were mainly involved in signal transduction process and ion channel-related pathways. Next, we integrated targets related to network topology parameters and targets of core pathways, identified PTGS2, EGFR, JUN, ESR1, TRPV1, AKT1 and VEGFA as butein regulated hub genes by molecular docking, which play a critical role in its analgesic effect. This study lays the scientific groundwork for elucidating the mechanism underlying butein's success in the treatment of BCP.

Sex differences in children's cognitive functions and phthalates exposure: a meta-analysis.

BACKGROUND: Phthalates exposure might affect children's intelligence development. This study aimed to determine (1) whether sex and age affect cognitive function and (2) whether sex differences in cognitive performance are wider with higher phthalate concentrations. METHODS: Data were collected from PubMed (1998-2022), PROQUEST (1997-2022), and SpringerLink (1995-2022). The study followed the PRISMA process. The included articles were followed by PECO framework. The GRADE applied to assess the certainty of evidence. Of 2422 articles obtained, nine were selected using inclusion criteria. The random-effects model was used to estimate the pooled effects. RESULTS: Our meta-regression indicated a significant difference between sex differences with age at phthalate concentration assessment (ß = -0.25; 95% CI = -0.47, -0.03) and MEHP concentration (ß = -0.20; 95% CI = -0.37, -0.03). CONCLUSIONS: The limitation of the current article is it only provides information on intelligence level rather than other aspects of cognitive function. Thus, the sequelae of phthalate exposure on attention and executive function are still unclear. Our analysis shows significant difference between sex differences in cognitive function scores associated with age at phthalate concentration assessment. Girls might be more resilient in cognitive function at a younger age or during lower concentrations of phthalates metabolites. IMPACT: This is the first meta-analysis to evaluate the pooled estimates of sex differences in objective cognitive functions among children with phthalate exposure. The female might be a protective factor when exposed to toxic plasticizers while the concentration is low. This study captures the possible role of sex in cognitive functioning and plasticizer exposure through a meta-analysis of children's sex, cognitive scores, and plasticizer exposure.

Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy.

PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE-/- mice.

Voltage-gated sodium channels, potential targets of Tripterygium wilfordii Hook. f. to exert activity and produce toxicity.

ETHNOPHARMACOLOGY RELEVANCE: Tripterygium wilfordii Hook. f. has been widely used in clinical practice due to its good anti-inflammatory and analgesic activities. However, its application is limited by potential toxicity and side effects. AIM OF THE STUDY: The study aimed to identify the mechanisms responsible for the pharmacological activity and cardiotoxicity of the main monomers of Tripterygium wilfordii. MATERIALS AND METHODS: Database analysis predicted that ion channels may be potential targets of Tripterygium wilfordii. The regulatory effects of monomers (triptolide, celastrol, demethylzeylasteral, and wilforgine) on protein Nav1.5 and Nav1.7 were predicted and detected by Autodock and patch clamping. Then, we used the formalin-induced pain model and evaluated heart rate and myocardial zymograms to investigate the analgesic activity and cardiotoxicity of each monomer in vivo. RESULTS: All four monomers were able to bind to Nav1.7 and Nav1.5 with different binding energies and subsequently inhibited the peak currents of both Nav1.7 and Nav1.5. The monomers all exhibited analgesic effects on formalin-induced pain; therefore, we hypothesized that Nav1.7 is one of the key analgesic targets. Demethylzeylasteral reduced heart rate and increased the level of creatine kinase-MB, thus suggesting a potential cardiac risk; data suggested that the inhibitory effect on Nav1.5 might be an important factor underlying its cardiotoxicity. CONCLUSION: Our findings provide an important theoretical basis for the further screening of active monomers with higher levels of activity and lower levels of toxicity.

Path sampling of recurrent neural networks by incorporating known physics.

Recurrent neural networks have seen widespread use in modeling dynamical systems in varied domains such as weather prediction, text prediction and several others. Often one wishes to supplement the experimentally observed dynamics with prior knowledge or intuition about the system. While the recurrent nature of these networks allows them to model arbitrarily long memories in the time series used in training, it makes it harder to impose prior knowledge or intuition through generic constraints. In this work, we present a path sampling approach based on principle of Maximum Caliber that allows us to include generic thermodynamic or kinetic constraints into recurrent neural networks. We show the method here for a widely used type of recurrent neural network known as long short-term memory network in the context of supplementing time series collected from different application domains. These include classical Molecular Dynamics of a protein and Monte Carlo simulations of an open quantum system continuously losing photons to the environment and displaying Rabi oscillations. Our method can be easily generalized to other generative artificial intelligence models and to generic time series in different areas of physical and social sciences, where one wishes to supplement limited data with intuition or theory based corrections.

A review of remote sensing for potato traits characterization in precision agriculture.

Potato is one of the most significant food crops globally due to its essential role in the human diet. The growing demand for potato, coupled with severe environmental losses caused by extensive farming activities, implies the need for better crop protection and management practices. Precision agriculture is being well recognized as the solution as it deals with the management of spatial and temporal variability to improve agricultural returns and reduce environmental impact. As the initial step in precision agriculture, the traditional methods of crop and field characterization require a large input in labor, time, and cost. Recent developments in remote sensing technologies have facilitated the process of monitoring crops and quantifying field variations. Successful applications have been witnessed in the area of precision potato farming. Thus, this review reports the current knowledge on the applications of remote sensing technologies in precision potato trait characterization. We reviewed the commonly used imaging sensors and remote sensing platforms with the comparisons of their strengths and limitations and summarized the main applications of the remote sensing technologies in potato. As a result, this review could update potato agronomists and farmers with the latest approaches and research outcomes, as well as provide a selective list for those who have the intentions to apply remote sensing technologies to characterize potato traits for precision agriculture.

Prediction and verification of potential lead analgesic and antiarrhythmic components in Corydalis yanhusuo W. T. Wang based on voltage-gated sodium channel proteins.

Corydalis yanhusuo W. T. Wang, a traditional Chinese herbal medicine, has been used as an analgesic for thousands of years and it also promotes blood circulation. In this study, 33 Corydalis yanhusuo alkaloid active components were acquired from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). A total of 543 pain-related targets, 1774 arrhythmia targets, and 642 potential targets of these active components were obtained using Swiss Target Prediction, GeneCards, Open Target Platform, and Therapeutic Target Database. Fifty intersecting targets were visualized through a Venn diagram, KEGG and GO pathway enrichment analysis. The analysis proposed that sodium ion channels are likely potential targets of Corydalis yanhusuo active components as analgesia and anti-arrhythmia agents. Molecular docking showed that the 33 components could bind to Nav1.7 and Nav1.5 (two subtypes of ion channel proteins) with different binding energies. In a patch clamp study, dihydrosanguinarine and dihydrochelerythrine, two monomers with the strongest binding effects, could inhibit the peak currents and promote both activation and inactivation phases of Nav1.5. Meanwhile, dihydrosanguinarine and dihydrochelerythrine could also inhibit peak currents and promote the activation phase of Nav1.7. Therefore, the findings from this study provide valuable information for future uses of traditional Chinese medicines to treat pain and cardiovascular disease.

Analysis of CFTR gene expression as an immunological and prognostic biomarker in pan-cancers.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel that regulates fluid homeostasis via ATP binding and uses energy to transport relevant substrates across cytomembranes. It has been reported that CFTR plays a crucial role in the incidence and development of various types of cancers by regulating proliferation, metastasis, invasion and apoptosis. However, aberrant CFTR gene expression across different cancers makes it difficult to propose CFTR as a possible pan-cancer biomarker. Here, multiple databases (ONCOMINE, PrognoScan, Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA)), were accessed to investigate the relationship between CFTR gene expression with the immunological and prognostic roles in pan-cancers. The results showed higher CFTR gene expression in tumor tissues compared to normal tissues for most cancers except for CHOL, ESCA, KICH, LAML, SKCM and STAD. Higher expression of the CFTR gene directly correlated with better prognosis for BRCA, GBM, COAD, KIRP, LAML, LUAD, PRAD, SARC and STAD, and CFTR gene expression was higher in stage Ⅰ_Ⅱ compared to stage Ⅲ_ Ⅳ. Furthermore, CFTR gene expression levels were significantly associated with immune infiltrates and immunocytes, in particular, immune checkpoints, in COAD, LIHC, LUAD and LUSC. In conclusion, CFTR can be used as a prognostic marker for nine types of cancers examined in this study where CFTR expression levels play a vital role in forecasting the clinical efficacy of immune checkpoint suppression therapy.

Gangliosides play important roles in the nervous system by regulating ion concentrations.

Gangliosides are important components of the neuronal cell membrane and play a vital role in the development of neurons and the brain. They participate in neurotransmission and are considered as the structural basis of learning and memory. Gangliosides participate in several and important physiological processes, such as cell differentiation, cell signaling, neuroprotection, nerve regeneration and apoptosis. The stability of ion concentration in excitable cells is particularly important in the maintenance of a steady state of cells and in the regulation of physiological functions. Ion concentration has been found to be related to the ganglioside's regulation in many neurological diseases, and several studies have found that they can stabilize intracellular ion concentration by regulating ion channels, which highlights their important regulatory role in neuronal excitability and synaptic transmission. Gangliosides can influence some forms of ion transport, by directly binding to ion transporters or through indirect binding and activation of transport proteins via appropriate signaling pathways. Therefore, the important and special role of gangliosides in the homeostasis of ion concentration is becoming a hot topic in the field and a theoretical basis in promoting help gangliosides use as key drugs for the treatment of nervous system diseases.

Associations of Social Jetlag with Dietary Behavior, Physical Activity and Obesity among Chinese Adolescents.

This study aimed to investigate the associations between social jetlag (SJL), dietary behavior, physical activity, and weight status in Chinese youth. Data were derived from a cross-sectional survey in Wuhan, China in 2019. Information on SJL, the frequency of food and beverage consumption, physical activity, and BMI category were collected via a self-reported questionnaire. The Kruskal-Wallis test and ANOVA were conducted to determine differences in daily consumption frequency of food and beverage groups, BMI category, and physical activity among SJL groups. Logistic regressions and restricted cubic splines were performed to test the association between SJL and the incidence of overweight or obesity. A final sample of 3567 Chinese adolescents [mean (SD) age, 14.67 (1.72) years; 47.41% (1691) female] were included. Our findings demonstrated that adolescents with SJL may consume more unhealthy foods and fewer beneficial foods, while engaging in less moderate to vigorous physical activity (MVPA) and reporting higher BMIs. In addition, adolescents who experience more than 2 h of SJL had significant greater risk of overweight or obesity. Our findings on SJL of Chinese adolescents confirm the harmful effects of SJL and also provide insights into the etiology of obesity in Chinese adolescents.

Body Mass Index, Waist Circumference, and Cognitive Decline Among Chinese Older Adults: A Nationwide Retrospective Cohort Study.

Background: The reported associations between body mass index (BMI), waist circumference (WC), and cognitive decline are not consistent, especially in older adults. Objective: This study aims to investigate the longitudinal associations of BMI, WC, and their change values with cognitive decline among Chinese adults aged 60 years and older and to examine the potential moderating effect of sex on these relationships. Methods: The participants in this study were from waves one to four (2011-2018) of the China Health and Retirement Longitudinal Study (CHARLS). Cognition function, BMI, and WC were measured at four examinations over 7 years. The interview-based cognitive assessments of memory, orientation and attention, and visuospatial ability were recorded. Standardized global cognitive scores were generated. BMI and WC were objectively measured. Mixed-effects models were performed to evaluate the associations. Results: A final sample of 3,035 Chinese older adults [mean (SD) age, 66.94 (5.43) years; 40.16% (n = 1,219) women] were included. Higher BMI (estimate = 0.0107; SE = 0.0024; p < 0.0001) and WC (estimate = 0.0019; SE = 0.0006; p = 0.0037) were associated with slower cognition score decline over a 7-year follow-up, while greater BMI variability (estimate = -0.0365; SE = 0.0116; p = 0.0017) was related to faster cognition score decline. The results were not modified by sex. BMI-defined overweight (estimate = 0.0094; SE = 0.0043; p = 0.0298) was associated with a slower cognition score decline, and both large weight gain (estimate = -0.0266; SE = 0.0074; p = 0.0003) and large WC loss (estimate = -0.0668; SE = 0.0329; p = 0.0426) were associated with faster cognition score decline. Conclusion: Among Chinese older adults, higher BMI, higher WC, and overweight are related to slower cognitive decline, while greater BMI variability, large weight gain, and large WC loss are associated with faster cognitive decline.

Immunosuppressive tumor-associated macrophages expressing interlukin-10 conferred poor prognosis and therapeutic vulnerability in patients with muscle-invasive bladder cancer.

BACKGROUND: Tumor-associated macrophages (TAMs) secreting IL-10 could be a specific functional cell subset with distinct polarization state and suppressive role in antitumor immune response. Here, we assessed the associations of clinical outcome, therapeutic responses and molecular features with IL-10+TAMs infiltration, and potential impact of IL-10+TAMs on the immune contexture in muscle-invasive bladder cancer (MIBC). METHODS: In this retrospective study, 128 patients and 391 patients with MIBC from Zhongshan hospital (ZS cohort) and The Cancer Genome Atlas cohort were included respectively. Immunohistochemistry was performed to quantify various immune cell infiltration in the ZS cohort. Single cell RNA sequencing and flow cytometry were performed to examine the functional status of IL-10+TAMs and its correlation with other immune cells. Survival analyses and assessment of the adjuvant chemotherapy (ACT) benefit analyses were also performed. RESULTS: High IL-10+TAMs infiltration was associated with inferior prognosis in terms of overall survival and recurrence-free survival, but superior chemotherapeutic response in MIBC. IL-10+TAMs with suppressive features were associated with immunoevasive tumor microenviroment characterized by exhausted CD8+ T cells, immature NK cells and increased immune checkpoint expression. Additionally, high IL-10+TAMs infiltration showed a strong linkage with basal-featured subtype and augmented EGF signaling. CONCLUSIONS: Immunosuppresive IL-10+TAMs contributed to an evasive contexture with incapacitated immune effector cells and increased immune checkpoint expression, therefore, predicting unfavorable clinical outcomes despite better ACT responsiveness. IL-10+TAMs might provide guidance for customized selection of EGFR-targeted therapy, FGFR3-targeted therapy as well as immunotherapy. The potential of immunosuppressive IL-10+TAMs as a therapeutic target is worth further exploration.