Lithium metal is the “holy grail” anode for next‐generation high‐energy rechargeable batteries due to its high capacity and lowest redox potential among all reported anodes. However, the practical ...application of lithium metal batteries (LMBs) is hindered by safety concerns arising from uncontrollable Li dendrite growth and infinite volume change during the lithium plating and stripping process. The formation of stable solid electrolyte interphase (SEI) and the construction of robust 3D porous current collectors are effective approaches to overcoming the challenges of Li metal anode and promoting the practical application of LMBs. In this review, four strategies in structure and electrolyte design for high‐performance Li metal anode, including surface coating, porous current collector, liquid electrolyte, and solid‐state electrolyte are summarized. The challenges, opportunities, perspectives on future directions, and outlook for practical applications of Li metal anode, are also discussed.
This review summarizes recent advances in stabilizing Li metal anodes via four effective strategies, including surface coating, porous current collector, liquid electrolyte, and solid‐state electrolyte. The aim is to provide a thorough and comprehensive overview of the recent development and applications of Li metal anodes to guide the future study of high‐safety, high‐stability, and high‐energy Li metal batteries.
The mutation and overexpression of the epidermal growth factor receptor (EGFR) are associated with the development of a variety of cancers, making this prototypical dimerization-activated receptor ...tyrosine kinase a prominent target of cancer drugs. Using long-timescale molecular dynamics simulations, we find that the N lobe dimerization interface of the wild-type EGFR kinase domain is intrinsically disordered and that it becomes ordered only upon dimerization. Our simulations suggest, moreover, that some cancer-linked mutations distal to the dimerization interface, particularly the widespread L834R mutation (also referred to as L858R), facilitate EGFR dimerization by suppressing this local disorder. Corroborating these findings, our biophysical experiments and kinase enzymatic assays indicate that the L834R mutation causes abnormally high activity primarily by promoting EGFR dimerization rather than by allowing activation without dimerization. We also find that phosphorylation of EGFR kinase domain at Tyr845 may suppress the intrinsic disorder, suggesting a molecular mechanism for autonomous EGFR signaling.
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► EGFR kinase is intrinsically disordered in the dimerization interface ► Cancer mutations stabilize the interface, promoting EGFR dimerization ► High activity of EGFR cancer mutants is due primarily to enhanced dimerization ► Phosphorylation similarly promotes dimerization and allows autonomous signaling
A prevalent EGFR mutation linked to lung cancer was previously thought to promote activation of the monomeric form of the receptor. A combination of biochemical and long-timescale molecular dynamics experiments now provides evidence that this mutation promotes ligand-independent dimerization by stabilizing receptors' dimerization interface.
Introduction Neighborhood social cohesion has been linked with better health and health behaviors, but its association with patterns of preventive healthcare use remains understudied. The hypothesis ...was that people with higher perceived neighborhood social cohesion would display increased use of preventive healthcare services. Methods Participants (N=7,168) were drawn from the 2006 wave of the Health and Retirement Study—a prospective and nationally representative panel study of American adults aged >50 years—and tracked for one wave (2 years). Analyses were conducted in 2016. Results After adjusting for sociodemographic factors and baseline health, each SD increase in neighborhood social cohesion was associated with a higher likelihood that people would obtain influenza vaccinations (OR=1.09, 95% CI=1.04, 1.15) or cholesterol tests (OR=1.10, 95% CI=1.02, 1.19). Further, women were more likely to receive mammograms/x-rays (OR=1.10, 95% CI=1.01, 1.19) or Pap tests (OR=1.08, 95% CI=1.00, 1.17). However, men were not more likely to receive prostate exams (OR=1.06, 95% CI=0.96, 1.17). Conclusions With additional research, findings from this study may inform the development of new strategies that increase the use of preventive healthcare services and enhance the quality of life among people moving through the ranks of this aging society.
Purpose in life has been linked with better health (mental and physical) and health behaviors, but its link with patterns of health care use are understudied. We hypothesized that people with higher ...purpose would be more proactive in taking care of their health, as indicated by a higher likelihood of using preventive health care services. We also hypothesized that people with higher purpose would spend fewer nights in the hospital. Participants ( n = 7,168) were drawn from the Health and Retirement Study, a nationally representative panel study of American adults over the age of 50, and tracked for 6 y. After adjusting for sociodemographic factors, each unit increase in purpose (on a six-point scale) was associated with a higher likelihood that people would obtain a cholesterol test odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.08–1.29 or colonoscopy (OR = 1.06, 95% CI = 0.99–1.14). Furthermore, females were more likely to receive a mammogram/X-ray (OR = 1.27, 95% CI = 1.16–1.39) or pap smear (OR = 1.16, 95% CI = 1.06–1.28), and males were more likely to receive a prostate examination (OR = 1.31, 95% CI = 1.18–1.45). Each unit increase in purpose was also associated with 17% fewer nights spent in the hospital (rate ratio = 0.83, 95% CI = 0.77–0.89). An increasing number of randomized controlled trials show that purpose in life can be raised. Therefore, with additional research, findings from this study may inform the development of new strategies that increase the use of preventive health care services, offset the burden of rising health care costs, and enhance the quality of life among people moving into the ranks of our aging society.
Significance Less than 50% of people over the age of 65 are up-to-date with core preventive services. Identifying modifiable factors linked with preventive services are important targets for research and practice. Purpose in life, recently the focus of multiple intervention studies, has been linked with better health (mental and physical) as well as improved health behaviors. However, its association with health care use has been understudied. We found that higher purpose was linked with greater use of several preventive health care services and also fewer nights spent hospitalized. These results may facilitate the development of new strategies to increase use of preventive health care services and improve health, thereby offsetting the burden of rising health care costs in our aging society.
Despite a growing interest in development of non-cytotoxic targeted agents, systemic chemotherapy is still the mainstay of treatment for both non-small cell lung cancer (NSCLC) and small cell lung ...cancer (SCLC). However, chemotherapy resistance limits our ability to effectively treat advanced lung cancer. Some lung tumors are intrinsically resistant to chemotherapy, and in virtually all cases, even the initial responders rapidly develop acquired resistance. While targeting histology could result in enhanced tumor sensitivity to a particular chemotherapeutic agent, better understanding of molecular determinants of chemotherapy sensitivity/resistance would be critically important. Development of predictive biomarkers to personalize chemotherapeutic agents and combining novel agents targeting specific resistance pathways with standard chemotherapy could be some promising strategies to overcome chemotherapy resistance in lung cancer. In this chapter, we will discuss some key mechanisms of resistance for commonly used chemotherapeutic agents in lung cancer.
Accumulating evidence shows that a higher sense of purpose in life is associated with lower risk of chronic conditions and premature mortality. Health behaviors might partially explain these ...findings, however, the prospective association between sense of purpose and health behaviors is understudied. We tested whether a higher sense of purpose at baseline was associated with lower likelihood of developing unhealthy behaviors over time. Prospective data were from the Health and Retirement Study, a national sample of U.S. older adults. Our sample included 13,770 adults assessed up to five times across eight years. Among people who met recommended guidelines for a given health behavior outcome at baseline, those in the top versus lowest quartile of purpose in life had 24% lower likelihood of becoming physically inactive (95% CI: 0.68–0.85), 33% lower likelihood of developing sleep problems (95% CI: 0.58–0.79), and 22% lower likelihood of developing unhealthy body mass index (BMI) (95% CI: 0.69–0.87) in sociodemographic-adjusted models. Further there was a marginal reduction in smoking relapse (HR = 0.65, 95% CI: 0.41–1.03) and no association with heavy alcohol use (HR = 1.02, 95% CI: 0.81–1.29). Findings for physical inactivity, sleep problems, and unhealthy BMI remained evident after further adjusting for baseline health status and depression. Our results, suggest that a sense of purpose in life might emerge (with further research) as a valuable target to consider for interventions aimed at helping older adults maintain some health behaviors.
•Pathways underlying the purpose-physical health association remain unclear.•We evaluated associations between purpose in life and several health behaviors.•We tested this hypothesis in a large and prospective cohort of adults aged >50.•Higher purpose was associated with lower risk of becoming physically inactive.•And also lower risk of developing sleep problems and unhealthy BMI
Although the thermodynamic principles that control the binding of drug molecules to their protein targets are well understood, detailed experimental characterization of the process by which such ...binding occurs has proven challenging. We conducted relatively long, unguided molecular dynamics simulations in which a ligand (the cancer drug dasatinib or the kinase inhibitor PP1) was initially placed at a random location within a box that also contained a protein (Src kinase) to which that ligand was known to bind. In several of these simulations, the ligand correctly identified its target binding site, forming a complex virtually identical to the crystallographically determined bound structure. The simulated trajectories provide a continuous, atomic-level view of the entire binding process, revealing persistent and noteworthy intermediate conformations and shedding light on the role of water molecules. The technique we employed, which does not assume any prior knowledge of the binding site’s location, may prove particularly useful in the development of allosteric inhibitors that target previously undiscovered binding sites.
Abstract
Background
Religious-service attendance has been linked with a lower risk of all-cause mortality, suicide and depression. Yet, its associations with other health and well-being outcomes ...remain less clear.
Methods
Using longitudinal data from three large prospective cohorts in the USA, this study examined the association between religious-service attendance and a wide range of subsequent physical health, health behaviour, psychological distress and psychological well-being outcomes in separate cohorts of young, middle-aged and older adults. All analyses adjusted for socio-demographic characteristics, prior health status and prior values of the outcome variables whenever data were available. Bonferroni correction was used to correct for multiple testing.
Results
Estimates combining data across cohorts suggest that, compared with those who never attended religious services, individuals who attended services at least once per week had a lower risk of all-cause mortality by 26% 95% confidence interval (CI): 0.65 to 0.84, heavy drinking by 34% (95% CI: 0.59 to 0.73) and current smoking by 29% (95% CI: 0.63 to 0.80). Service attendance was also inversely associated with a number of psychological-distress outcomes (i.e. depression, anxiety, hopelessness, loneliness) and was positively associated with psychosocial well-being outcomes (i.e. positive affect, life satisfaction, social integration, purpose in life), but was generally not associated with subsequent disease, such as hypertension, stroke, and heart disease.
Conclusions
Decisions on religious participation are generally not shaped principally by health. Nevertheless, for individuals who already hold religious beliefs, religious-service attendance may be a meaningful form of social integration that potentially relates to greater longevity, healthier behaviours, better mental health and greater psychosocial well-being.
Defining cellular and molecular identities within the kidney is necessary to understand its organization and function in health and disease. Here we demonstrate a reproducible method with minimal ...artifacts for single-nucleus Droplet-based RNA sequencing (snDrop-Seq) that we use to resolve thirty distinct cell populations in human adult kidney. We define molecular transition states along more than ten nephron segments spanning two major kidney regions. We further delineate cell type-specific expression of genes associated with chronic kidney disease, diabetes and hypertension, providing insight into possible targeted therapies. This includes expression of a hypertension-associated mechano-sensory ion channel in mesangial cells, and identification of proximal tubule cell populations defined by pathogenic expression signatures. Our fully optimized, quality-controlled transcriptomic profiling pipeline constitutes a tool for the generation of healthy and diseased molecular atlases applicable to clinical samples.
A 50-year-old woman with persistent axillary lymphadenopathy 17 weeks after COVID-19 vaccination was ultimately diagnosed with biopsy-proven benign reactive lymphadenopathy. In contrast, a ...60-year-old woman with axillary lymphadenopathy and concurrent suspicious breast findings 9 weeks after COVID-19 vaccination was ultimately diagnosed with biopsy-proven metastatic breast carcinoma. This article reviews the current guidelines regarding breast cancer screening and management of axillary lymphadenopathy in the setting of COVID-19 vaccination.
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