Authenticated social capital: conceptualising power, resistance and well-being in the lives of transgender older adults.

Trans people experience social marginalisation, stigmatisation and violent oppression in US society and worldwide. Given the importance of social capital for wellbeing, this study sought to illuminate the ways in which trans people build social capital throughout their lives and to use this knowledge to promote new and helpful ways of thinking about social capital concerning the human life course in the 21st century. We conducted a secondary interpretive content analysis of 86 in-depth interviews with trans older adults generated as part of the arts project To Survive on This Shore. Trans older adults confront social marginalisation and stigmatisation by generating what we call authenticated social capital, a form of social capital built by re-negotiating social constraints and developing alternative social networks and supports that affirm identity and foster authenticity and wellbeing. These networks and supports are often embedded in social worlds created by trans people that facilitate gender affirmation and social activism through community organising. The concept of authenticated social capital integrates and expands upon paradigmatic understandings of social capital. In addition to enhancing theorising and interventions aimed at improving the lives of trans people, the approach may be well suited to conceptualising the life experiences and liberation of other oppressed groups.

AKR1C1 connects autophagy and oxidative stress by interacting with SQSTM1 in a catalytic-independent manner.

Targeting autophagy might be a promising anticancer strategy; however, the dual roles of autophagy in cancer development and malignancy remain unclear. NSCLC (non-small cell lung cancer) cells harbour high levels of SQSTM1 (sequestosome 1), the autophagy receptor that is critical for the dual roles of autophagy. Therefore, mechanistic insights into SQSTM1 modulation may point towards better approaches to treat NSCLC. Herein, we used multiple autophagy flux models and autophagy readouts to show that aldo-keto reductase family 1 member C1 (AKR1C1), which is highly expressed in NSCLC, promotes autophagy by directly binding to SQSTM1 in a catalytic-independent manner. This interaction may be strengthened by reactive oxygen species (ROS), important autophagy inducers. Further mechanistic research demonstrated that AKR1C1 interacts with SQSTM1 to augment SQSTM1 oligomerization, contributing to the SQSTM1 affinity for binding cargo. Collectively, our data reveal a catalytic-independent role of AKR1C1 for interacting with SQSTM1 and promoting autophagy. All these findings not only reveal a novel functional role of AKR1C1 in the autophagy process but also indicate that modulation of the AKR1C1-SQSTM1 interaction may be a new strategy for targeting autophagy.

Avoiding Structural Collapse to Reduce Lead Leakage in Perovskite Photovoltaics.

Perovskite solar cells (PSCs) have become a promising candidate for the next-generation photovoltaic technologies. As an essential element for high-efficiency PSCs however, the heavy metal Pb is soluble in water, causing a serious threat to the environment and human health. Due to the weak ionic bonding in three-dimensional (3D) perovskites, drastic structure decomposition occurs when immersing the perovskite film in water, which accelerates the Pb leakage. By introducing the chemically stable Dion-Jacobson (DJ) 2D perovskite at the 3D perovskite surface, the film dissolution is significantly slowed down, which retards lead leakage. As a result, the Pb contamination is dramatically reduced under various extreme conditions. In addition, the PSCs device deliver a power conversion efficiency (PCE) of 23.6 % and retain over 95 % of their initial PCE after the maximum power point tracking for over 1100 h.

Within-couple dissimilarities in functional impairment as determinants of spousal care arrangement among older married couples.

Existing research on spousal care focuses on one spouse receiving care from the other, which fails to address the complexity that is created when both spouses experience some impairments. Our study included situations in which one or both spouses have functional impairments when examining the extent to which spouses from the same couple hold a (dis)similar level of functional impairment and whether such within-couple (dis)similarity has an impact on the spousal care arrangement. A subsample of 1170 older married couples was selected from the 2014 Health and Retirement Study. Descriptive statistics were used for describing the level of each spouse's functional impairment regarding the number of limitations in activities (activities of daily living [ADL]) or instrumental ADL (IADL). Logistic regressions were used to examine whether spousal dissimilarity in functional impairment (dissimilar, similarly low, similarly high) was associated with spousal care arrangement. Within couples with one functionally impaired spouse, the impaired spouse was more likely to receive spousal care when reporting a higher level of ADL/IADL impairment. Within couples with two functionally impaired spouses, the more impaired person was more likely to receive spousal care (without giving back) when spouses reported dissimilar level of IADL impairment; spouses were more likely to report mutual care when they had similarly high levels of IADL impairment. By documenting the role of spousal dissimilarities in functioning for determining spousal care arrangement, our study can inform couple-based interventions that capitalize on each spouse's capabilities and resources.

CD161+CD127+CD8+ T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus.

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127-CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.

Josephin domain containing 2 (JOSD2) promotes lung cancer by inhibiting LKB1 (Liver kinase B1) activity.

Non-small cell lung cancer (NSCLC) ranks as one of the leading causes of cancer-related deaths worldwide. Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment, these drugs are suitable for and beneficial to a mere ~30% of NSCLC patients. Consequently, the need for novel strategies addressing NSCLC remains pressing. Deubiquitinases (DUBs), a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets. Nevertheless, the mechanisms by which DUBs promote NSCLC remain poorly understood. Through a global analysis of the 97 DUBs' contribution to NSCLC survival possibilities using The Cancer Genome Atlas (TCGA) database, we found that high expression of Josephin Domain-containing protein 2 (JOSD2) predicted the poor prognosis of patients. Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo. Mechanically, we found that JOSD2 restricts the kinase activity of LKB1, an important tumor suppressor generally inactivated in NSCLC, by removing K6-linked polyubiquitination, an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex. Notably, we identified the first small-molecule inhibitor of JOSD2, and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo. Our findings highlight the vital role of JOSD2 in hindering LKB1 activity, underscoring the therapeutic potential of targeting JOSD2 in NSCLC, especially in those with inactivated LKB1, and presenting its inhibitors as a promising strategy for NSCLC treatment.

The Role of Contextual Factors in Shaping Urban Older Adults' Intention of Institutional Care in China: A Mixed-Methods Study.

BACKGROUND: This mixed-methods study explores older people's intention of institutional care and its contributing contextual factors, and the meaning given to their intention by older adults in the transitioning Chinese society. METHODS: Guided by the extended Anderson model and frameworks of the ecological theory of aging, survey data collected from 1937 Chinese older adults were used. Transcripts from six focus group interviews were analyzed to incorporate the voices of the participants. RESULTS: Community environment and services, health services, financial services, and regional service organizations were related to the institutional care intention of older people. The qualitative analysis showed that the reported conflicting feelings about institutional care was driven by the lack of supporting resources and age-friendly environment. The findings of this study suggested that the reported intention of Chinese older adults for institutional care may not be an ideal choice but a compromise or, in some cases, a forced choice. CONCLUSIONS: Rather than treating the stated institutional intention as a simple expression of older Chinese people's likes or desires, the intention of institutional care should be understood within a framework that fully considers the influence of psycho-social factors and contextual organizations.

Efficacy and surgical safety of sequential surgical resection after pembrolizumab plus chemotherapy for initial unresectable stage IIIB non-small cell lung cancer.

INTRODUCTION: Neoadjuvant immunochemotherapy is effective in resectable NSCLC. However, its role in unresectable stage IIIB NSCLC patients remains controversial. This study aimed to demonstrate the efficacy and safety of neoadjuvant immunochemotherapy followed by surgical resection to treat initial unresectable stage IIIB NSCLC patients. METHODS: This study retrospectively analyzed 59 initial unresectable stage IIIB NSCLC patients who received induction pembrolizumab combined with chemotherapy between June 2019 and April 2022. Clinical characteristics, radiological and pathological responses, and survival outcomes were collected and evaluated. RESULTS: Fifity-nine initial unresectable stage IIIB NSCLC patients were identified and divided into surgery (n = 23) and non-surgery (n = 36) groups with a median follow-up time of 15.0 months. The median PFS/DFS of the surgery group was significantly longer than the non-surgery group (not reached vs. 15.5 months, p = 0.0031). The median overall survival (OS) was not reached in both groups, and the OS rate was 100% (23/23) in the surgery group and 83.3% (30/36) in the non-surgery group. The pathological analysis suggested that 13 of 23 patients (56.5%) achieved major pathological response (MPR) or pathological complete response (pCR), and more squamous cell carcinoma cases were observed in the MPR group compared to the non-MPR group (p = 0.034). All patients in the surgery group had an R0 resection, and no surgical-related mortality was recorded; only three patients (13.0%) experienced any postoperative complications. CONCLUSION: In this retrospective study, surgical resection after neoadjuvant immunochemotherapy was promising for initial unresectable stage IIIB NSCLC patients, with a high MPR rate and good surgical safety.

Neighborhood resources associated with frailty trajectories over time among community-dwelling older adults in China.

BACKGROUND AND OBJECTIVES: Recent research has identified neighborhoods as an important contributor to later-life frailty. However, little is known about how neighborhood resources are associated with frailty trajectories over time, especially in developing countries. This study examines the impact of neighborhood physical and social resources on the trajectories of frailty over time among older people in China. RESEARCH DESIGN AND METHODS: Using the four waves of the China Health and Retirement Longitudinal Study (2011-2018), 5673 respondents aged 60 and above at baseline were included for analyses. Multilevel growth modeling was fitted to estimate the effects of neighborhood resources on frailty trajectories over a 7-year period, controlling for individual-level characteristics. RESULTS: Older Chinese people who lived in neighborhoods with better basic infrastructures and a greater number of voluntary organizations were less frail at baseline. Accessible exercise facilities were associated with a lower initial level of frailty only among rural older adults, while higher community-level socioeconomic status (SES) was associated with a lower initial level of frailty only among urban older adults. Over the 7-year follow-up period, better basic infrastructures and accessible exercise facilities were associated with a slower increase rate of frailty scores among rural residents. DISCUSSION AND IMPLICATIONS: Neighborhood resources are important contributors to the level of frailty among older Chinese people. Our findings of significant urban-rural differences have important implications for designing and implementing infrastructure development and community building programs in rural and urban China.

Deubiquitinating enzymes: Promising targets for drug resistance.

Drug resistance to chemotherapy and molecularly targeted therapies is a current challenge in cancer treatments. The underlying mechanisms of resistance to cytotoxic chemotherapeutics and to drugs that target a specific molecule are not understood completely. In recent years, emerging evidence has frequently suggested that the dysregulation of deubiquitinating enzymes (DUBs) plays important roles in the development of drug resistance. We focus on the molecular mechanisms through which DUBs enable cancer cells to escape cell death and survive when exposed to a variety of anti-cancer drugs. Furthermore, this review summarizes the potential application of DUB inhibitors in combination therapies to overcome drug resistance.

Neighborhood Effects on the Health of Chinese Older Adults: Beyond the Rural and Urban Dichotomy.

BACKGROUND AND OBJECTIVES: The associations between physical frailty and depressive symptoms among older individuals were established in the existing literature. Taking the person-environment perspective, we argue that neighborhood environment could either buffer the stress derived from being physically vulnerable or worsen it by adding another layer of stressors in the environmental context when physical health declined. The objectives of this study were to explore to what extent the neighborhood-level characteristics moderate the relationship between physical frailty and depressive symptoms. RESEARCH DESIGN AND METHODS: Using the China Health and Retirement Longitudinal Study 2011 wave, 6,245 individuals aged 60 years and older were included for analyses. Multilevel mixed-effects models were fitted to examine the moderating effects of urbanicity and neighborhood-level socioeconomic status (SES) on the relationship between frailty and depressive symptoms among older adults, controlling for individual-level characteristics. RESULTS: Results showed a stronger relationship between deterioration in physical health and depressive symptoms in rural neighborhoods and neighborhoods with lower SES, after controlling for individual-level SES. Also, the moderating effects of the neighborhood-level socioeconomic factors remained after controlling for urbanicity, indicating that neighborhood SES works beyond the rural-urban contexts. DISCUSSION AND IMPLICATIONS: Findings from this study demonstrate the important roles of neighborhood socioeconomic characteristics in reshaping, and the need to redefine, China's rural-urban dichotomy. The findings also identified neighborhoods with low SES as potential targets for policy and practice to reduce the stress associated with health decline.

Initially Negative Affect Predicts Lower Satisfaction With Future Social Contact: A Time-Lagged Analysis Using Ecological Momentary Assessment.

OBJECTIVES: Prior research has linked subjective features of social situations with short-term changes in affect (e.g., across days, hours), but little is known about the directionality of such links. Our study examined the concurrent and lead-lag relationships between social contact satisfaction and affect in the flow of daily life. METHOD: Using ecological momentary assessment (EMA), wherein 78 late-middle-aged and older adults reported on 2,739 social contacts (average 5.02 per day, SD = 2.95) across seven consecutive days, we examined how the level of social contact satisfaction was concurrently and prospectively associated with affect (high-arousal and low-arousal positive affect [PA], high-arousal and low-arousal negative affect [NA]). RESULTS: Higher contact satisfaction was concurrently associated with more high- and low-arousal PA and less high- and low-arousal NA. The influence of contact satisfaction remains for predicting greater low-arousal PA (quietness, calmness) during the next social contact. NA (either high- or low-arousal) predicted lower satisfaction during the next social contact, but such sustainable influence was not observed for PA. DISCUSSION: The study reveals a cycle in which elevated NA may trigger unsatisfactory social contact, which subsequently predicted less low-arousal PA such as quietness and calmness. Our study provided a more nuanced and differentiated picture of the temporal sequencing of everyday social contact and momentary affect. Practitioners may gain insights from our study into the development of just-in-time adaptive interventions that aim for the betterment of affective well-being in old age.

Machado-Joseph Deubiquitinases: From Cellular Functions to Potential Therapy Targets.

Ubiquitination is known as important post-translational modification in cancer-related pathways. Human deubiquitinases (DUBs), with functions of modulating the ubiquitination process, are a family with about 100 proteins. They mainly function by cutting ubiquitin chains of the substrates. The Machado-Joseph domain-containing proteases (MJDs) is one of the sub-families of DUBs, consisting of four members, namely, Ataxin-3, Ataxin-3L, JOSD1, and JOSD2. Recent studies have provided new insights into biological functions of MJDs in the progression of Machado-Joseph disease or cancer diseases. In this review, we summarized the cellular functions and regulatory mechanisms of MJDs in Machado-Joseph disease and cancer pathways. Furthermore, we summarized MJDs genetic alterations in different human cancers by exploring the public databases (cBioportal). The aim of this review is to provide a comprehensive account based on our current knowledge about emerging insights into MJDs in physiology and disease, which might shed light on fundamental biological questions and promise to provide a potential target for therapeutic intervention.

Development and Validation of a Prognostic Tool for Identifying Residents at Increased Risk of Death in Long-Term Care Facilities.

BACKGROUND: To promote better care at the end stage of life in long-term care facilities, a culturally appropriate tool for identifying residents at the end of life is crucial. OBJECTIVE: This study aimed to develop and validate a prognostic tool, the increased risk of death (IRD) scale, based on the minimum data set (MDS). DESIGN: A retrospective study using data between 2005 and 2013 from six nursing homes in Hong Kong. SETTING/SUBJECTS: A total of 2380 individuals were randomly divided into two equal-sized subsamples: Sample 1 was used for the development of the IRD scale and Sample 2 for validation. MEASUREMENTS: The measures were MDS 2.0 items and mortality data from the discharge tracking forms. The nine items in the IRD scale (decline in cognitive status, decline in activities of daily living, cancer, renal failure, congestive heart failure, emphysema/chronic obstructive pulmonary disease, edema, shortness of breath, and loss of weight), were selected based on bivariate Cox proportional hazards regression. RESULTS: The IRD scale was a strong predictor of mortality in both Sample 1 (HRsample1 = 1.50, 95% confidence interval [CI]: 1.37-1.65) and Sample 2 (HRsample2 = 1.31, 1.19-1.43), after adjusting for covariates. Hazard ratios (HRs) for residents who had an IRD score of 3 or above for Sample 1 and Sample 2 were 3.32 (2.12-5.21) and 2.00 (1.30-3.09), respectively. CONCLUSIONS: The IRD scale is a promising tool for identifying nursing home residents at increased risk of death. We recommend the tool to be incorporated into the care protocol of long-term care facilities in Hong Kong.