Inflammatory Role of CCR1 in the Central Nervous System.

BACKGROUND: Chemokine ligands and their corresponding receptors are essential for regulating inflammatory responses. Chemokine receptors can stimulate immune activation or inhibit/promote signaling pathways by binding to specific chemokine ligands. Among these receptors, CC chemokine receptor 1 (CCR1) is extensively studied as a G protein-linked receptor target, predominantly expressed in various leukocytes, and is considered a promising target for anti-inflammatory therapy. Furthermore, CCR1 is essential for monocyte extravasation and transportation in inflammatory conditions. Its involvement in inflammatory diseases of the central nervous system (CNS), including multiple sclerosis, Alzheimer's disease, and stroke, has been extensively studied along with its ligands. Animal models have demonstrated the beneficial effects resulting from inhibiting CCR1 or its ligands. SUMMARY: This review demonstrates the significance of CCR1 in CNS inflammatory diseases, the molecules implicated in the inflammatory pathway, and potential drugs or molecules for treating CNS diseases. This evidence may offer new targets or strategies for treating inflammatory CNS diseases.

Selective deficiency of UCP-1 and adropin may lead to different subtypes of anti-neutrophil cytoplasmic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease that is prone to respiratory and renal failures. Its major target antigens are serine protease 3 (PR3) and myeloperoxidase (MPO), but the determinants of PR3 and MPO subtypes are still unclear. Uncoupling protein-1 (UCP-1) and adropin (Adr) regulate mutually and play an important role in endothelial cell injury. In this study, adropin and UCP-1 knockout (AdrKO and UCP-1-KO) models were established on the basis of C57BL/6 J mice. The results showed that UCP-1-KO and AdrKO mice similar to AAV: significant inflammatory cell infiltration, vascular wall damage, and erythrocyte extravasation. The pathological basis of AdrKO was that endothelial cells adhered and activated neutrophils to release MPO, and the core gene was peroxisome proliferator-activated receptor gamma (PPARG). However, UCP-1-KO induced PR3 release, and the accumulation and expression of tissue factor on the vascular wall, and the core gene was peroxisome proliferator-activated receptor delta (PPARD). The present study verified that the subtypes of AAV may be genetically different diseases and it also provide novel experimental evidence for clinical differentiation of the two subtypes.

Inhibition of CCR2 attenuates neuroinflammation and neuronal apoptosis after subarachnoid hemorrhage through the PI3K/Akt pathway.

BACKGROUND: Neuroinflammation and neuronal apoptosis are closely associated with a poor prognosis in patients with subarachnoid hemorrhage (SAH). We investigated the role of C-C motif chemokine receptor 2 (CCR2) in SAH. METHODS: Pre-processed RNA-seq transcriptome datasets GSE167110 and GSE79416 from the Gene Expression Omnibus (GEO) database were screened for genes differentially expressed between mice with SAH and control mice, using bioinformatics analysis. The endovascular perforation model was performed to establish SAH. RS504393 (a CCR2 antagonist) and LY294002 (PI3K inhibitor) were administered to explore the mechanism of neuroinflammation after SAH. SAH grading, neurological scoring, brain water content and blood-brain barrier (BBB) permeability determination, enzyme-linked immunosorbent assay (ELISA), western blotting, and immunofluorescence were performed. An in vitro model of SAH was induced in H22 cells by hemin treatment. The protective mechanism of CCR2 inhibition was studied by adding RS504393 and LY294002. Clinical cerebrospinal fluid (CST) samples were detected by ELISA. RESULTS: Expression of CCR2 was upregulated in both datasets and was identified as a hub gene. CCR2 expression was significantly upregulated in the cytoplasm of neurons after SAH, both in vitro and in vivo. RS significantly reduced the brain water content and blood-brain barrier permeability, alleviated neuroinflammation, and reduced neuronal apoptosis after SAH. Additionally, the protective effects of CCR2 inhibition were abolished by LY treatment. Finally, the levels of CCR2, inflammatory factors, and apoptotic factors were elevated in the CSF of patients with SAH. CCR2 levels were associated with patient outcomes at the 6-month follow-up. CONCLUSION: CCR2 expression was upregulated in both in vitro and in vivo SAH models. Additionally, inhibition of CCR2, at least partly through the PI3K/AKT pathway, alleviated neuroinflammation and neuronal apoptosis in vivo and in vitro. CCR2 levels in the CSF have a moderate diagnostic value for 6-month outcome prediction in patients with SAH.

Plasmonic gold nanojets fabricated by a femtosecond laser irradiation.

Gold nanojets with various morphologies, from nanopillar to nanotip with up to 800 nm height, and finally to nanotip with droplet, are fabricated on gold thin film by a femtosecond laser irradiation. The near-field localized surface plasmon resonance (LSPR) and photothermal effects of gold nanojets are studied through finite element electromagnetic (EM) analysis, supporting in nanojets design for potential applications of high-resolution imaging, nanomanipulation and sensing. For an individual nanotip, the confined electron oscillations in LSPR lead to an intense local EM field up to three orders of magnitude stronger than the incident field strength at the end of gold tip, where the vertical resolution for the field enhancement was improved down to nanoscale due to the small size of the sharp gold tip (5-nm-radius). At specific wavelength, nanopillar can serve as an effective light-to-heat converter and its heating can be fine-tuned by external irradiation, and its dimension. The long-range periodic nanojet arrays (periods from 1.5 µm to 2.5 µm) with different geometry were printed using several pulse energy levels. By confining more light into the tip (two orders of magnitude stronger than single tip), nanotip array shows more pronounced potential to serve as a refractometric sensor due to their high sensitivity and reproducibility. These results promote fs laser printing as a high-precision tool for nanoarchitecture in optical imaging, nanomanipulation and sensing application.

Epidemiological Analysis of 1234 Cases of Laryngeal Cancer in Shanxi Province, China.

BACKGROUND: Laryngeal cancer is a common malignancy of the head and neck, especially in northern China, including Shanxi province. This study intends to describe the epidemiological characteristics of laryngeal cancer in Shanxi Province, China, in order to support prevention and treatment efforts. METHODS: Retrospective analysis of the medical records of patients diagnosed with laryngeal cancer in hospitals in Shanxi Province from 2008 to 2012. RESULTS: The average annual incidence rate of laryngeal cancer in Shanxi province from 2008 to 2012 was 0.70/105, the Chinese population standardized incidence rate was 0.57/105 and the world population standardized incidence rate was 0.60/105. The city with the highest incidence of laryngeal cancer in Shanxi Province is Taiyuan, followed by Yangquan, and the lowest incidence are Yuncheng and Jincheng. The cases included 723 farmers (58.6%), 338 workers (27.4%), 95 government cadres (7.7%), 35 unemployed individuals (2.8%), 30 teachers (2.4%) and 13 individuals with other occupations (1.1%). The incidence of laryngeal cancer in rural areas was 0.78/105, while urban areas was 0.60/105. Of 1006 patients with smoking and drinking status reported, there were 238 both smoking and drinking (23.7%), 491 only smoking but not drinking (48.8%), 4 only drinking but not smoking (0.4%), 273 both not smoking and not drinking (27.1%) (P<0.001), and there were 695 males smoking (95.3%), 34 females smoking (4.7%) (P<0.001). Of 879 patients for whom the primary cancer location was known, 406 cases (46.2%) were supraglottic and 428 cases (48.7%) were glottic. Among 1009 patients with known pathological classification, the vast majority had squamous cell carcinoma (992 cases, 98.3%). CONCLUSIONS: To sum up, the incidence of laryngeal cancer in Shanxi Province exhibited a relatively stable trend from 2008 to 2012, and the incidence is higher in men than in women in all years. The high percentage of smokers in this study underscores the importance of smoking as a risk factor for laryngeal cancer, whereas rates of drinking did not appear to be linked. Incidence of laryngeal cancer was higher in rural areas than in urban areas, a pattern that differs from other regions of China and internationally.

Indirect competitive-structured electrochemical immunosensor for tetrabromobisphenol A sensing using CTAB-MnO2 nanosheet hybrid as a label for signal amplification.

Tetrabromobisphenol A (TBBPA) is a kind of brominated flame retardant that is usually added to products to reduce their flame retardancy. However, its extensive use has resulted in their residues being found in the environment, which is very harmful. Herein, an indirect competitive immunosensor has been established for TBBPA detection based on the signal amplification system. Pd nanospheres in situ reduced on the surface of MnO2 nanosheet hybrid (MnO2/Pd) was used as the label for the secondary antibody through the Pd-N bond, and gold-toluidine blue composite was loaded onto MWCNTs (MWCNTs/Au-TB), which functioned as the platform for the immunosensor. The spherical structure of Pd had abundant catalytic active sites, which enhanced the catalytic activity of MnO2/Pd as the label, hence amplifying the signal response. Besides, MWCNTs/Au-TB improved electron transfer and produced a strong signaling pathway for immobilizing antigens through the Au-NH2 bond, which can specifically recognize primary antibodies to improve sensitivity. The immunosensor had a linear concentration range of 0-81 ng/mL, a low detection limit of 0.17 ng/mL (S/N = 3), with good stability, selectivity, and reproducibility based on the above advantages. Additionally, the acceptable accuracy and recoveries (recoveries, 92-124%; CV, 3.3-8.8%) in the real water sample analysis indicated that this strategy is promising for emerging pollutant analysis.

Timing considerations for removal of early cumulus cells in short-term insemination strategies.

Context The timing of early cumulus cell removal (ECCR) can be changed within a range. The change has an effect on the multiple pronuclei (MPN) rate and the exposure time of oocytes to sperm waste products. The timing of ECCR effects the outcomes of assisted reproductive technology, however, it is still unclear what time is best for ECCR. Aims To find the best time for ECCR based on clinical outcomes in order to increase the success rate of assisted reproductive technology. Methods A retrospective study was performed. Cycles were categorised into six groups according to the timing of ECCR. The clinical outcomes of these six groups were compared by Kruskal-Wallis test and Pearson X 2 test. Key results The timing of ECCR had a significant effect on the MPN rate, 0PN without cleavage rate and grade 1-2 embryo rate at Day3. Among our six time groups of ECCR, the cumulus cell removal ≤4h post-insemination group had the highest MPN rate and grade 1-2 embryo rate at Day3, and the 5.5h

Petroleum extract of Farfarae Flos alleviates nasal symptoms by regulating the Th1-Th2 cytokine balance in a mouse model of Allergic Rhinitis.

Farfarae Flos is a traditional Chinese medicine that has long been used to treat allergies. In this study, we aimed to investigate the effect of a petroleum extract of Farfarae Flos (PEFF) in a mouse model of allergic rhinitis (AR) and to explore the underlying molecular mechanisms of action. An animal model of AR was established by sensitization and challenge of BALB/c mice with ovalbumin (OVA). PEFF was administered intranasally and AR nasal symptoms were assessed on a semi-quantitative scale according to the frequencies of nose rubbing and sneezing and the degree of rhinorrhea. The mechanism of action of PEFF was evaluated by histological analysis of nasal mucosa architecture and inflammatory status; ELISA-based quantification of serum OVA-specific IgE, interferon-γ (IFN-γ), and interleukin-4 (IL-4) concentrations; and immunohistochemical and western blot analysis of T-bet and GATA3 protein expression in nasal mucosa and spleen tissues. The results showed intranasal administration of PEFF alleviated AR symptom scores and reduced both the infiltration of inflammatory cells and tissue damage in the nasal mucosa. PEFF significantly decreased serum concentrations of OVA-specific IgE (P<0.01) and IL-4 (P<0.05) and significantly increased IFN-γ (P<0.01). PEFF also upregulated the expression of T-bet protein (P<0.05) but downregulated GATA3 protein (P<0.05) in nasal mucosa and spleen tissues. In conclusion, PEFF effectively reduces AR nasal symptoms and serum IgE levels in a mouse model and may act by correcting the imbalance between Th1 and Th2 responses.

Platelet Antibodies in Infertility Patients.

BACKGROUND: Platelet antigens can stimulate the body to produce platelet alloimmune antibodies through blood transfusion, pregnancy, and autoimmunity. In the blood of pregnant women, anti-platelet antibodies can cause embryo implantation failure, abortion, etc. if they are present. METHODS: The platelet antibody was screened in 326 infertile patients (282 primary infertility and 44 secondary infertility) and 522 healthy controls in the physical examination center of our hospital by solid phase agglutination of red blood cells. RESULTS: The positive rate of anti-platelet antibody was 9.51% in the infertility group and 2.30% in the healthy control group. There was a significant difference between them (χ2 = 4.51, p < 0.05). The positive rate of anti-platelet antibody in the infertility group was significantly higher than that in the control group. The positive rate of anti-platelet antibody in the secondary infertility patients was significantly higher than that in the primary infertility patients (χ2 = 1.62, p < 0.05), and the positive rate of serum anti-platelet antibody increased gradually with the increase of infertility years. CONCLUSIONS: The positive rate of anti-platelet antibody is closely related to infertility and gradually increases with the age of infertility.

circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant tumor in head and neck. Autophagy and circular RNAs (circRNAs) play critical roles in cancer progression and chemoresistance. However, the function and mechanism of circRNA in autophagy regulation of LSCC remain unclear. METHODS: The autophagy-suppressive circRNA circPARD3 was identified via RNA sequencing of 107 LSCC tissues and paired adjacent normal mucosal (ANM) tissues and high-content screening. RT-PCR, Sanger sequencing, qPCR and fluorescence in situ hybridization were performed to detect circPARD3 expression and subcellular localization. Biological functions of circPARD3 were assessed by proliferation, migration, invasion, autophagic flux, and chemoresistance assays using in vitro and in vivo models. The mechanism of circPARD3 was investigated by RNA immunoprecipitation, RNA pulldown, luciferase reporter assays, western blotting and immunohistochemical staining. RESULTS: Autophagy was inhibited in LSCC, and circPARD3 was upregulated in the LSCC tissues (n = 100, p < 0.001). High circPARD3 level was associated with advanced T stages (p < 0.05), N stages (p = 0.001), clinical stages (p < 0.001), poor differentiation degree (p = 0.025), and poor prognosis (p = 0.002) of LSCC patients (n = 100). Functionally, circPARD3 inhibited autophagy and promoted LSCC cell proliferation, migration, invasion and chemoresistance. We further revealed that activation of the PRKCI-Akt-mTOR pathway through sponging miR-145-5p was the main mechanism of circPARD3 inhibited autophagy, promoting LSCC progression and chemoresistance. CONCLUSION: Our study reveals that the novel autophagy-suppressive circPARD3 promotes LSCC progression and chemoresistance through the PRKCI-Akt-mTOR pathway, providing new insights into circRNA-mediated autophagy regulation and potential biomarker and target for LSCC treatment.

Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck. LSCC patients have seriously impaired vocal, respiratory, and swallowing functions with poor prognosis. Circular RNA (circRNA) has attracted great attention in cancer research. However, the expression patterns and roles of circRNAs in LSCC remain largely unknown. METHODS: RNA sequencing was performed on 57 pairs of LSCC and matched adjacent normal mucosa tissues to construct circRNA, miRNA, and mRNA expression profiles. RT-PCR, qPCR, Sanger sequencing, and FISH were undertaken to study the expression, localization, and clinical significance of circCORO1C in LSCC tissues and cells. The functions of circCORO1C in LSCC were investigated by RNAi-mediated knockdown, proliferation analysis, EdU staining, colony formation assay, Transwell assay, and apoptosis analysis. The regulatory mechanisms among circCORO1C, let-7c-5p, and PBX3 were investigated by luciferase assay, RNA immunoprecipitation, western blotting, and immunohistochemistry. RESULTS: circCORO1C was highly expressed in LSCC tissues and cells, and this high expression was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circCORO1C inhibited the proliferation, migration, invasion, and in vivo tumorigenesis of LSCC cells. Mechanistic studies revealed that circCORO1C competitively bound to let-7c-5p and prevented it from decreasing the level of PBX3, which promoted the epithelial-mesenchymal transition and finally facilitated the malignant progression of LSCC. CONCLUSIONS: circCORO1C has an oncogenic role in LSCC progression and may serve as a novel target for LSCC therapy. circCORO1C expression has the potential to serve as a novel diagnostic and prognostic biomarker for LSCC detection.

Mass spectrometry-based proteomic analysis of FSCN1-interacting proteins in laryngeal squamous cell carcinoma cells.

Fascin actin-bundling protein 1 (FSCN1) is an evolutionarily conserved actin-bundling protein that plays a critical role in cell migration, motility, adhesion, and cellular interactions. Although multiple clinical studies have implicated the expression of FSCN1 in laryngeal squamous cell carcinoma (LSCC) progression, the precise mechanism of FSCN1 in the process has not been clearly elucidated. To define FSCN1 function, we characterized FSCN1­interacting proteins in two cell lines by immunoprecipitation followed by mass spectrometry (MS). After data filtering, 119 proteins with expression in both the Hep-2 and TU-177 cell samples were identified as FSCN1-interacting partners. With in-depth bioinformatics analysis, we linked FSCN1 to critical cellular processes including cell adhesion, glycolysis/gluconeogenesis, regulation of protein ubiquitination, ribosomal RNA processing, and small molecule metabolism. We discuss the interactions between FSCN1 and some of the newly validated partners. The identification of these potential partners of FSCN1 expands our knowledge of the FSCN1 interactome and provides a valuable resource for understanding the functions of this protein in LSCC progression.

The role of EXT1 gene mutation and its high expression of calcitonin gene-related peptide in the development of multiple exostosis.

OBJECTIVE: Screening and identifying the gene mutation of EXT1, EXT2 and EXT3 associated with multiple exostosis (ME) and the expression in tumor tissues. METHODS: Nine patients with multiple exostosis were collected and genomic DNA was extracted. Polymerase chain reaction (PCR) amplification and direct sequencing techniques were used to screen all exons, 5' and 3' ends of the EXT1, EXT2 and EXT3 related causative genes. EXT1, EXT2 and EXT3 gene were screened and quantified by RNA-SEQ and RT-qPCR. The concentration of calcitonin gene-related peptide (CGRP) in peripheral blood of tumor patients and normal controls was detected by ELISA. RESULTS: Between the two patients with ME, the EXT1 gene was found in one patient to have c.79 T>A mutation, which caused the change of p.M27T, the non polar methionine was replaced by the high frequency mutation of polar threonine, and the rest of patients was found the splicing mutation c.1284 + 8 delAT of the heterozygosity of the EXT1 gene. The serum CGRP concentration of ME patients (623 + 49 pg/ml) was significantly higher than that of normal controls (196 + 68 pg/ml), and EXT1 mutation patients were also higher than non mutation patients.

Does Medical Insurance Integration Reduce Frailty Risk? Evidence From Rural Older Adults in China.

OBJECTIVES: This study aimed to assess the impacts of China's health insurance integration reform on frailty among rural older adults. METHODS: Nationally representative longitudinal data with 2,751 adults aged ≥60 years were analyzed from the China Health and Retirement Longitudinal Study 2011-2015. The integration of the rural New Cooperative Medical Scheme and urban Resident Basic Medical Insurance into the unified Urban and Rural Resident Basic Medical Insurance (URRBMI). Frailty Index (FI) summarizes 32 health deficits, quantifying frailty severity with a range of 0-1. Frailty is defined as FI ≥ 0.25, prefrailty as FI: 0.10-0.25, and robustness as FI < 0.10. Frailty worsening, stability, and improvement from 2011 to 2015 were assessed. Difference-in-differences and propensity score matched difference-in-differences models assessed URRBMI integration effects on frailty severity and risk (FI ≥ 0.25) among rural older adults. RESULTS: URRBMI integration significantly reduced frailty severity by 15.16% and risk by 9.60% points among rural older adults. Reductions were greatest among initially prefrail individuals, with 27.49% lower frailty severity and a 17.62% point reduction in subsequent frailty onset risk after URRBMI integration. In contrast, no significant benefits were observed for initially robust or frail subgroups following integration. Analyses of frailty transitions corroborated selective benefits, with URRBMI integration lowering the risks of worsening frailty among prefrail but no significant reversal of frailty status among those initially frail or prefrail. DISCUSSION: China's URRBMI integration selectively ameliorated frailty progression among rural older adults with prefrail status. Targeting integrated medical insurance policies toward high-risk populations may optimize frailty prevention effects.

Effects of China's Clean Air Act on Frailty Levels Among Middle-Aged and Older Adults: A Population-Based Quasi-Experimental Study.

BACKGROUND: Air pollution is a frailty risk factor, yet the frailty-related health benefits of China's air pollution control policy, the Clean Air Action (CCAA), are unclear. Frailty progression and transitions differ among robust, prefrail, and frail adults. This study aimed to evaluate the CCAA's effect on frailty levels among robust, prefrail, and frail Chinese adults. METHODS: Using propensity score matching with difference-in-differences analysis, we studied 9 788 adults aged ≥45 from the 2011 and 2018 China Health and Retirement Longitudinal Study. The Frailty Index (FI), summarizing 32 health deficits, quantifies frailty level (range: 0-1 scores). Frailty was defined as FI ≥ 0.25, prefrailty as FI 0.10-0.25, and robust as FI ≤ 0.10. We examined frailty transitions between these states (robust, prefrail, and frail) from 2011 to 2018. Based on provincial particulate matter reduction targets, participants were assigned to intervention (>10% reduction) or control (≤10%) groups and categorized as robust, prefrail, or frail pre-CCAA implementation. RESULTS: The CCAA significantly reduced FI scores among preimplementation robust individuals by 0.0205 and among prefrail individuals by 0.0114, with no significant changes in frail individuals. Frailty transition analyses confirmed specific benefits of the CCAA, which significantly reduced worsening from robust to prefrail or frail by 7.0% and prefrail to frail by 3.9%. However, it did not facilitate the improvement from frail to prefrail/robust or from prefrail back to robust. No significant subgroup differences were observed across age, gender, Hukou, education, and social participation. CONCLUSIONS: CCAA has been associated with a reduction in frailty deterioration in robust and prefrail populations.

Spousal education and frailty levels among Chinese older adults: A national longitudinal study.

Background: Prior research has identified one's own education level as a risk factor for frailty. However, the association between spousal education and frailty in later life is uncertain. We aim to examine the longitudinal association between spousal education and frailty levels among Chinese older populations. Methods: 3856 participants aged 60 and older from the 2011-2018 China Health and Retirement Longitudinal Study were analyzed. A 54-item deficit cumulative frailty index was developed to evaluate frailty levels at each follow-up. Linear mixed-effects models were used to examine the longitudinal association of spousal education with frailty levels, and whether this association varied by sex and own education level. Results: Higher spouse education was associated with lower frailty levels, and this association decreased with age. Compared with older adults whose spouses had no formal education, older adults whose spouses had less than middle school education had an 8.82 lower level of frailty (95% CI: 15.05 to -2.58, P < 0.01); those with spouses with middle school education and above had a 23.44 lower level (95% CI: 31.43 to -15.44, P < 0.001). Stratified analysis showed that every additional year of spouse education was also associated with lower frailty levels in non-frail participants at baseline, but stronger among those already frail. The association between high spousal education and lower frailty did not vary by sex or own education. Conclusion: This study reveals a significant association between having a more educated spouse and lower later-life frailty levels for both older men and women, regardless of one's own educational background. It emphasizes the importance of leveraging educated spouses to prevent and manage frailty.

Can Social Mobility Impact Frailty Trajectories of Chinese Adults in Later Life? A Nationwide Longitudinal Study.

Background and Objectives: Evidence remains unclear on the impact of life-course socioeconomic position (SEP) mobility on frailty trajectories in later life. We aim to examine the longitudinal effects of social mobility on frailty trajectories among Chinese middle-aged and older populations. Research Design and Methods: A total of 13 239 participants aged 45 and older from the 2011-2018 China Health and Retirement Longitudinal Study were analyzed. Based on changes in SEP from childhood to adulthood, 5 patterns of social mobility were established. A 32-item deficit cumulative frailty index (FI) was developed to evaluate frailty trajectories at each follow-up. Linear mixed-effects models were used to examine the longitudinal association of the 5 social mobility patterns with the frailty trajectory. Results: The trajectory of late-life FI increased across all 5 social mobility groups during the follow-up. The FI trajectory had the largest disparity between stable high SEP and stable low SEP, with a faster increase in FI of 0.489 (95% confidence interval [CI]: 0.327-0.650, p < .001) in the stable low versus stable high SEP group. The FI trajectories of individuals in the upward and downward mobility groups fall between those in the stable high SEP and low SEP groups. Specifically, compared to the stable high SEP group, the increase in FI was 0.229 (95% CI: 0.098-0.360, p = .001) faster in the downward mobility group, and 0.145 (95% CI: 0.017-0.273, p = .03) faster in the upward mobility group. The impact of social mobility on frailty trajectories was more pronounced among middle-aged adults and women. Discussion and Implications: These findings emphasize that policies to identify vulnerable populations and reduce frailty inequalities should focus on the socioeconomic environment across the life course, with particular attention paid to those with consistently low SEP and downward mobility.

Perforin 1 in Cancer: Mechanisms, Therapy, and Outlook.

PRF1 (perforin 1) is a key cytotoxic molecule that plays a crucial role in the killing function of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Recent studies have focused on PRF1's role in cancer development, progression, and prognosis. Studies have shown that aberrant PRF1 expression has a significant role to play in cancer development and progression. In some cancers, high expression of the PRF1 gene is associated with a better prognosis for patients, possibly because it helps enhance the body's immune response to tumors. However, some studies have also shown that the absence of PRF1 may make it easier for tumors to evade the body's immune surveillance, thus affecting patient survival. Furthermore, recent studies have explored therapeutic strategies based on PRF1, such as enhancing the ability of immune cells to kill cancer cells by boosting PRF1 activity. In addition, they have improved the efficacy of immunotherapy by modulating its expression to enhance the effectiveness of the treatment. Based on these findings, PRF1 may be a valuable biomarker both for the treatment of cancer and for its prognosis in the future. To conclude, PRF1 has an important biological function and has clinical potential for the treatment of cancer, which indicates that it deserves more research and development in the future.