A pan-cancer single-cell panorama of human natural killer cells.

Natural killer (NK) cells play indispensable roles in innate immune responses against tumor progression. To depict their phenotypic and functional diversities in the tumor microenvironment, we perform integrative single-cell RNA sequencing analyses on NK cells from 716 patients with cancer, covering 24 cancer types. We observed heterogeneity in NK cell composition in a tumor-type-specific manner. Notably, we have identified a group of tumor-associated NK cells that are enriched in tumors, show impaired anti-tumor functions, and are associated with unfavorable prognosis and resistance to immunotherapy. Specific myeloid cell subpopulations, in particular LAMP3+ dendritic cells, appear to mediate the regulation of NK cell anti-tumor immunity. Our study provides insights into NK-cell-based cancer immunity and highlights potential clinical utilities of NK cell subsets as therapeutic targets.

A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis.

Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites1-6 (for example, suppressing severe systemic inflammation6-9). Since the 1970s, an emerging organizational rule about these reflexes has been the presence of body-region specificity1-6. For example, ES at the hindlimb ST36 acupoint but not the abdominal ST25 acupoint can drive the vagal-adrenal anti-inflammatory axis in mice10,11. The neuroanatomical basis of this somatotopic organization is, however, unknown. Here we show that PROKR2Cre-marked sensory neurons, which innervate the deep hindlimb fascia (for example, the periosteum) but not abdominal fascia (for example, the peritoneum), are crucial for driving the vagal-adrenal axis. Low-intensity ES at the ST36 site in mice with ablated PROKR2Cre-marked sensory neurons failed to activate hindbrain vagal efferent neurons or to drive catecholamine release from adrenal glands. As a result, ES no longer suppressed systemic inflammation induced by bacterial endotoxins. By contrast, spinal sympathetic reflexes evoked by high-intensity ES at both ST25 and ST36 sites were unaffected. We also show that optogenetic stimulation of PROKR2Cre-marked nerve terminals through the ST36 site is sufficient to drive the vagal-adrenal axis but not sympathetic reflexes. Furthermore, the distribution patterns of PROKR2Cre nerve fibres can retrospectively predict body regions at which low-intensity ES will or will not effectively produce anti-inflammatory effects. Our studies provide a neuroanatomical basis for the selectivity and specificity of acupoints in driving specific autonomic pathways.

Associations of the EAT-Lancet reference diet with metabolic dysfunction-associated steatotic liver disease and its severity: A multicohort study.

BACKGROUND AND AIMS: The EAT-Lancet Commission devised a globally sustainable dietary pattern to jointly promote human health and sustainability. However, the extent to which this diet supports metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been assessed. This study aimed to investigate the association between the EAT-Lancet diet and the risk of MASLD and its severity. APPROACH AND RESULTS: This prospective multicohort study included 15,263 adults from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort, 1137 adults from the Guangzhou Nutrition and Health Study (GNHS) cohort, and 175,078 adults from the UK Biobank. In addition, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included. An EAT-Lancet diet index was created to reflect adherence to the EAT-Lancet reference diet. The TCLSIH cohort recorded 3010 MASLD cases during 53,575 person-years of follow-up, the GNHS cohort documented 624 MASLD cases during 6454 person-years of follow-up, and the UK Biobank developed 1350 MASLD cases during 1,745,432 person-years of follow-up. In multivariable models, participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles (TCLSIH: HR = 0.87, 95% CI: 0.78, 0.96; GNHS: HR = 0.79, 95% CI: 0.64, 0.98; UK Biobank: HR = 0.73, 95% CI: 0.63, 0.85). Moreover, liver-controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (ß = -5.895; 95% CI: -10.014, -1.775). CONCLUSIONS: Adherence to the EAT-Lancet reference diet was inversely associated with the risk of MASLD as well as its severity.

A circuit from lateral hypothalamic to dorsal hippocampal dentate gyrus modulates behavioral despair in mice.

Behavioral despair is one of the clinical manifestations of major depressive disorder and an important cause of disability and death. However, the neural circuit mechanisms underlying behavioral despair are poorly understood. In a well-established chronic behavioral despair (CBD) mouse model, using a combination of viral tracing, in vivo fiber photometry, chemogenetic and optogenetic manipulations, in vitro electrophysiology, pharmacological profiling techniques, and behavioral tests, we investigated the neural circuit mechanisms in regulating behavioral despair. Here, we found that CBD enhanced CaMKIIα neuronal excitability in the dorsal dentate gyrus (dDG) and dDGCaMKIIα neurons involved in regulating behavioral despair in CBD mice. Besides, dDGCaMKIIα neurons received 5-HT inputs from median raphe nucleus (MRN) and were mediated by 5-HT1A receptors, whereas MRN5-HT neurons received CaMKIIα inputs from lateral hypothalamic (LH) and were mediated by AMPA receptors to regulate behavioral despair. Furthermore, fluvoxamine exerted its role in resisting behavioral despair through the LH-MRN-dDG circuit. These findings suggest that a previously unidentified circuit of LHCaMKIIα-MRN5-HT-dDGCaMKIIα mediates behavioral despair induced by CBD. Furthermore, these support the important role of AMPA receptors in MRN and 5-HT1A receptors in dDG that might be the potential targets for treatment of behavioral despair, and explain the neural circuit mechanism of fluvoxamine-resistant behavioral despair.

MTNR1B genotype and effects of carbohydrate quantity and dietary glycaemic index on glycaemic response to an oral glucose load: the OmniCarb trial.

AIMS/HYPOTHESIS: A type 2 diabetes-risk-increasing variant, MTNR1B (melatonin receptor 1B) rs10830963, regulates the circadian function and may influence the variability in metabolic responses to dietary carbohydrates. We investigated whether the effects of carbohydrate quantity and dietary glycaemic index (GI) on glycaemic response during OGTTs varied by the risk G allele of MTNR1B-rs10830963. METHODS: This study included participants (n=150) of a randomised crossover-controlled feeding trial of four diets with high/low GI levels and high/low carbohydrate content for 5 weeks. The MTNR1B-rs10830963 (C/G) variant was genotyped. Glucose response during 2 h OGTT was measured at baseline and the end of each diet intervention. RESULTS: Among the four study diets, carrying the risk G allele (CG/GG vs CC genotype) of MTNR1B-rs10830963 was associated with the largest AUC of glucose during 2 h OGTT after consuming a high-carbohydrate/high-GI diet (ß 134.32 [SE 45.69] mmol/l × min; p=0.004). The risk G-allele carriers showed greater increment of glucose during 0-60 min (ß 1.26 [0.47] mmol/l; p=0.008) or 0-90 min (ß 1.10 [0.50] mmol/l; p=0.028) after the high-carbohydrate/high-GI diet intervention, but not after consuming the other three diets. At high carbohydrate content, reducing GI levels decreased 60 min post-OGTT glucose (mean -0.67 [95% CI: -1.18, -0.17] mmol/l) and the increment of glucose during 0-60 min (mean -1.00 [95% CI: -1.67, -0.33] mmol/l) and 0-90 min, particularly in the risk G-allele carriers (pinteraction <0.05 for all). CONCLUSIONS/INTERPRETATION: Our study shows that carrying the risk G allele of MTNR1B-rs10830963 is associated with greater glycaemic responses after consuming a diet with high carbohydrates and high GI levels. Reducing GI in a high-carbohydrate diet may decrease post-OGTT glucose concentrations among the risk G-allele carriers.

Cardiovascular Health and Life Expectancy Among Adults in the United States.

BACKGROUND: Cardiovascular disease may be the main reason for stagnant growth in life expectancy in the United States since 2010. The American Heart Association recently released an updated algorithm for evaluating cardiovascular health (CVH)-Life's Essential 8 (LE8) score. We aimed to quantify the associations of CVH levels, estimated by the LE8 score, with life expectancy in a nationally representative sample of US adults. METHODS: We included 23 003 nonpregnant, noninstitutionalized participants aged 20 to 79 years who participated in the National Health and Nutrition Examination Survey from 2005 to 2018 and whose mortality was identified through linkage to the National Death Index through December 31, 2019. The overall CVH was evaluated by the LE8 score (range, 0-100), as well as the score for each component of diet, physical activity, tobacco/nicotine exposure, sleep duration, body mass index, non-high-density lipoprotein cholesterol, blood glucose, and blood pressure. Life table method was used to estimate life expectancy by levels of the CVH. RESULTS: During a median of 7.8 years of follow-up, 1359 total deaths occurred. The estimated life expectancy at age 50 years was 27.3 years (95% CI, 26.1-28.4), 32.9 years (95% CI, 32.3-33.4), and 36.2 years (95% CI, 34.2-38.2) in participants with low (LE8 score <50), moderate (50≤ LE8 score <80), and high (LE8 score ≥80) CVH, respectively. Equivalently, participants with high CVH had an average 8.9 (95% CI, 6.2-11.5) more years of life expectancy at age 50 years compared with those with low CVH. On average, 42.6% of the gained life expectancy at age 50 years from adhering to high CVH was attributable to reduced cardiovascular disease death. Similarly significant associations of CVH with life expectancy were observed in men and women, respectively. Similarly significant associations of CVH with life expectancy were observed in White participants and Black participants but not in Mexican participants. CONCLUSIONS: Adhering to a high CVH, defined as the LE8 score, is related to a considerably increased life expectancy in US adults, but more research needs to be done in other races and ethnicities (eg, Hispanic and Asian).

Sulfonic Acid-Functionalized Graphdiyne for Effective Li-S Battery Separators.

Lithium-sulfur (Li-S) batteries enable a promising high-energy-storage system while facing practical challenges regarding lithium dendrites and lithium polysulfides (LiPSs) shuttling. Herein, a fascinating SO3H-functionalized graphdiyne (SOGDY) was developed by grafting SO3H onto GDY to modify the separator in Li-S batteries. It realizes structure-retained material transformation, that is, SOGDY retains the crystalline all-carbon network and uniform subnanopores from the initial GDY. The abundant SO3H and uniform pores create a rapid Li+ transport relay station, benefit rapid Li+ transport and even lithium deposition, and prevent lithium dendrite growth. The spatial obstruction and strong polar adsorption sites from SO3H effectively inhibit LiPS shuttling. Additionally, SOGDY establishes a fast electron-transfer pathway to facilitate the LiPS conversion. The SOGDY/PP separator exhibited steady cycling at 1 mA cm-2 over 3500 h in the Li∥Li symmetric battery and achieved outstanding low-temperature and high-rate performance in the Li-S battery with a high initial specific capacity of 804.5 mA h g-1 and a final capacity of 504.9 mA h g-1 after 500 cycles at 3 C and -10 °C. This work demonstrates that introducing a stable all-carbon network and uniform functionalized nanopores is an effective strategy to modify the Li-S battery separator.

Record Second-Harmonic Generation and Birefringence in an Ultraviolet Antimonate by Bond Engineering.

Oxides have attracted considerable attention owing to their potential for nonlinear optical (NLO) applications. Although significant progress has been achieved in optimizing the structural characteristics of primitives (corresponding to the simplest constituent groups, namely, cations/anions/neutral molecules) comprising the crystalline oxides, the role of the primitives' interaction in determining the resultant functional structure and optical properties has long been underappreciated and remains unclear. In this study, we employ a π-conjugated organic primitive confinement strategy to manipulate the interactions between primitives in antimonates and thereby significantly enhance the optical nonlinearity. Chemical bonds and relatively weak H-bonding interactions promote the formation of cis- and trans-Sb(III)-based dimer configurations in (C5H5NO)(Sb2OF4) (4-HPYSOF) and (C5H7N2)(Sb2F7) (4-APSF), respectively, resulting in very different second-harmonic generation (SHG) efficiencies and birefringences. In particular, 4-HPYSOF displays an exceptionally strong SHG response (12 × KH2PO4 at 1064 nm) and a large birefringence (0.513 at 546 nm) for a Sb(III)-based NLO oxide as well as a UV cutoff edge. Structural analyses and theoretical studies indicate that polarized ionic bond interactions facilitate the favorable arrangement of both the inorganic and organic primitives, thereby significantly enhancing the optical nonlinearity in 4-HPYSOF. Our findings shed new light on the intricate correlations between the interactions of primitives, inorganic primitive configuration, and SHG properties, and, more broadly, our approach provides a new perspective in the development of advanced NLO materials through the interatomic bond engineering of oxides.

Controlled Growth of Metal Atom Arrays on Graphdiyne for Seawater Oxidation.

Advanced atomic-level heterointerface engineering provides a promising method for the preparation of next-generation catalysts. Traditional carbon-based heterointerface catalytic performance rely heavily on the undetermined defects in complex and demanding preparation processes, rendering it impossible to control the catalytic performance. Here, we present a general method for the controlled growth of metal atom arrays on graphdiyne (GDY/IrCuOx), and we are surprised to find strong heterointerface strains during the growth. We successfully controlled the thickness of GDY to regulate the heterointerface metal atoms and achieved compressive strain at the interface. Experimental and density functional theory calculation results show that the unique incomplete charge transfer between GDY and metal atoms leads to the formation of strong interactions and significant heterointerface compressive strain between GDY and IrCuOx, which results in high oxidation performances with 1000 mA cm-2 at a low overpotential of 283 mV and long-term stability at large current densities in alkaline simulated seawater. We anticipate that this finding will contribute to construction of high-performance heterogeneous interface structures, leading to the development of new generation of GDY-based heterojunction catalysts in the field of catalysis for future promising performance.

Adulthood weight changes, body mass index in youth, genetic susceptibility and risk of atrial fibrillation: a population-based cohort study.

BACKGROUND: Epidemiological evidence on weight change and atrial fibrillation (AF) remains limited and inconsistent. Previous studies on body mass index (BMI) in youth and AF rarely considered subsequent BMI. This study aimed to assess the associations of AF with weight change and BMI in youth, as well as modified effect by genetic susceptibility of AF. METHODS: The study included 21,761 individuals (mean age 57.8 years) from the Malmö Diet and Cancer cohort. Weight information was obtained at three time points, including recalled weight at age 20 years, measured weight at baseline (middle adulthood), and reported weight at 5-year follow-up examination (late middle adulthood). A weighted genetic risk score of AF was created using 134 variants. RESULTS: During a median follow-up of 23.2 years, a total of 4038 participants developed AF. The association between weight change from early to middle adulthood and AF risk was modified by sex (Pinteraction = 0.004); weight loss was associated with a lower AF risk in females, but not in males. Conversely, weight gain was positively associated with AF risk in a linear manner in females, whereas increased AF risk appeared only when weight gain exceeded a threshold in males. Participants with weight gain of > 5 kg from middle to late middle adulthood had a 19% higher risk of AF relative to those with stable weight, whereas weight loss showed a null association. Compared to individuals with a lower BMI at age 20 years, those with a BMI above 25 kg/m2 had an increased risk of AF (HR = 1.14; 95% CI: 1.02-1.28), after controlling for baseline BMI; this association was more pronounced in males or those with a lower genetic risk of AF. CONCLUSIONS: Weight gain in middle adulthood was associated with higher AF risk. Weight loss from early to middle adulthood, but not from middle to late middle adulthood, was associated with a lower risk of AF only in females. Higher BMI in youth was associated with an increased risk of AF, particularly among males or those with a lower genetic risk of AF.

Assessing the impact of type 2 diabetes on mortality and life expectancy according to the number of risk factor targets achieved: an observational study.

BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of premature death. Whether multifactorial risk factor modification could attenuate T2D-related excess risk of death is unclear. We aimed to examine the association of risk factor target achievement with mortality and life expectancy among patients with T2D, compared with individuals without diabetes. METHODS: In this longitudinal cohort study, we included 316 995 participants (14 162 with T2D and 302 833 without T2D) free from cardiovascular disease (CVD) or cancer at baseline between 2006 and 2010 from the UK Biobank. Participants with T2D were categorised according to the number of risk factors within target range (non-smoking, being physically active, healthy diet, guideline-recommended levels of glycated haemoglobin, body mass index, blood pressure, and total cholesterol). Survival models were applied to calculate hazard ratios (HRs) for mortality and predict life expectancy differences. RESULTS: Over a median follow-up of 13.8 (IQR 13.1-14.4) years, deaths occurred among 2105 (14.9%) participants with T2D and 18 505 (6.1%) participants without T2D. Compared with participants without T2D (death rate per 1000 person-years 4.51 [95% CI 4.44 to 4.57]), the risk of all-cause mortality among those with T2D decreased stepwise with an increasing number of risk factors within target range (0-1 risk factor target achieved: absolute rate difference per 1000 person-years 7.34 [4.91 to 9.78], HR 2.70 [2.25 to 3.25]; 6-7 risk factors target achieved: absolute rate difference per 1000 person-years 0.68 [-0.62 to 1.99], HR 1.16 [0.93 to 1.43]). A similar pattern was observed for CVD and cancer mortality. The association between risk factors target achievement and all-cause mortality was more prominent among participants younger than 60 years than those 60 years or older (P for interaction = 0.012). At age 50 years, participants with T2D who had 0-1 and 6-7 risk factors within target range had an average 7.67 (95% CI 6.15 to 9.19) and 0.99 (-0.59 to 2.56) reduced years of life expectancy, respectively, compared with those without T2D. CONCLUSIONS: Individuals with T2D who achieved multiple risk factor targets had no significant excess mortality risk or reduction in life expectancy than those without diabetes. Early interventions aiming to promote risk factor modification could translate into improved long-term survival for patients with T2D.

Degree of joint risk factor control and hazard of mortality in diabetes patients: a matched cohort study in UK Biobank.

BACKGROUND: Diabetes patients are at higher risk for mortality than the general population; however, little is known about whether the excess mortality risk associated with diabetes could be mitigated or nullified via controlling for risk factors. METHODS: We included 18,535 diabetes patients and 91,745 matched individuals without diabetes without baseline cancer or cardiovascular disease (CVD), followed up from 2006 to 2021. The main exposure was the number of optimized risk factors including glycated hemoglobin < 53 mmol/mole, systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, no albuminuria, non-current smoking and low-density lipoprotein cholesterol (LDL-C) < 2.5 mmol/L. We used Cox proportional hazards models to explore the association of the degree of risk factor control with all-cause mortality, cancer mortality, CVD mortality and other mortality. RESULTS: Each additional risk factor control was associated with a 16, 10, 21 and 15% lower risk of all-cause mortality, cancer mortality, CVD mortality and other mortality, respectively. Optimal risk factors control (controlling 5 risk factors) was associated with a 50% (HR 0.50, 95% CI 0.41-0.62), 74% (HR 0.26, 95% CI 0.16-0.43) and 38% (HR 0.62, 95% CI 0.44-0.87) lower risk of all-cause mortality, CVD mortality and other mortality, respectively. Diabetes patients with 4, 3 and 5 or more controlled risk factors, respectively, showed no excess risk of all-cause mortality, cancer mortality and CVD mortality compared to matched non-diabetes patients. CONCLUSIONS: The results from this study indicate that optimal risk factor control may eliminate diabetes-related excess risk of all-cause mortality, CVD mortality and other mortality.

Microcrystalline Nanofiber Electrode with Adaptive Intrinsic Structure and Microscopic Interface.

A strategy of microcrystalline aggregation is proposed to fabricate energy storage electrode with outstanding capacity and stability. Carbon-rich electrode (BDTG) functionalized with benzo[1,2-b:4,5-b']dithiophene units and butadiyne segments are prepared. The linear conjugate chains pack as microcrystalline nanofibers on nanoscale, which further aggregates to form a porous interpenetrating network. The microcrystalline aggregation feature of BDTG exhibit stable structure during long cycling test, revealing the following advantage in structure and property. The stretchable butadiyne linker facilitates reversible adsorption and desorption of Li with the aid of adjacent sulfur heteroatom. The alkyne-alkene transition exhibits intrinsic structural stability of microcrystalline region in BDTG electrodes. Meanwhile, alkynyl groups and sulfur heteroatoms on the surface of BDTG nanofibers participate in the formation of microscopic interface, providing a stable interfacial contact between BDTG electrodes and adjacent electrolyte. As a proof-of-concept, BDTG-based electrode shows high capacity (1430 mAh g-1 at 50 mA g-1) and excellent cycle performance (8000 cycles under 5 A g-1) in half-cell of lithium-ion batteries, and a reversible capacity of 120 mAh g-1 is obtained under the current density of 2 C in full-cell. This work shows microcrystalline aggregation is beneficial to realize adaptive intrinsic structure and interface contact during the charge-discharge process.

A Multi-Interface Structure of Graphdiyne/Cobalt Oxides for Chlorine Production.

A challenge facing the chlor-alkali process is the lack of electrocatalyst with high activity and selectivity for the efficient industrial production of chlorine. Herein the authors report a new electrocatalyst that can generate multi-interface structure by in situ growth of graphdiyne on the surface of cobalt oxides (GDY/Co3O4), which shows great potential in highly selective and efficient chlorine production. This result is due to the strong electron transfer and high density charge transport between GDY and Co3O4 and the interconversion of the mixed valence states of the Co atoms itself. These intrinsic characteristics efficiently enhance the conductivity of the catalyst, facilitate the reaction kinetics, and improve the overall catalytic selectivity and activity. Besides, the protective effect of the formed GDY layer is remarkable endowing the catalyst with excellent stability. The catalyst can selectively produce chlorine in low-concentration of NaCl aqueous solution at room temperature and pressure with the highest Faraday efficiency of 80.67% and an active chlorine yield rate of 184.40 mg h-1 cm-2, as well as superior long-term stability.

Proteomic Signature of BMI and Risk of Cardiovascular Disease.

BACKGROUND: Obesity, defined by body mass index (BMI) alone, is a metabolically heterogeneous disorder with distinct cardiovascular manifestations across individuals. This study aimed to investigate the associations of a proteomic signature of BMI with risk of major subtypes of cardiovascular disease (CVD). METHODS: A total of 40 089 participants from UK Biobank, free of CVD at baseline, had complete data on proteomic data measured by the Olink assay. A BMI-proteomic score (pro-BMI score) was calculated from 67 pre-identified plasma proteins associated with BMI. RESULTS: A higher pro-BMI score was significantly associated with higher risks of ischemic heart disease (IHD) and heart failure (HF), but not with risk of stroke. Comparing the highest with the lowest quartiles, the adjusted hazard ratio (HR) for IHD was 1.49 (95% CI, 1.32-1.67) (P-trend < 0.001), and the adjusted HR for HF was 1.52 (95% CI, 1.25-1.85) (P-trend < 0.001). Further analyses showed that the association of pro-BMI score with HF risk was largely driven by the actual BMI, whereas the association of the pro-BMI score with IHD risk was independent of actual BMI and waist-to-hip ratio (WHR). The association between pro-BMI score and IHD risk appeared to be stronger in the normal BMI group than other BMI groups (P-interaction = 0.004) and stronger in the normal WHR group than the high WHR group (P-interaction = 0.049). CONCLUSIONS: Higher pro-BMI score is significantly associated with higher IHD risk, independent of actual BMI levels. Our findings suggest that plasma proteins hold promise as complementary markers for diagnosing obesity and may facilitate personalized interventions.

Smoking Timing, Healthy Diet, and Risk of Incident CKD Among Smokers: Findings From UK Biobank.

RATIONALE & OBJECTIVE: Although smoking is a recognized risk factor for chronic kidney disease (CKD), the relationship between the time smoking is initiated after awakening each day and CKD remains largely unstudied. This study examined the association between this timing and the risk of CKD, and the potential interactions of smoking timing with other risk factors for the occurrence of CKD. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A total of 32,776 participants in the UK Biobank with complete data on the time from waking to the first cigarette and free of prevalent CKD were included. EXPOSURE: Time from waking to the first cigarette. OUTCOME: Incident CKD cases. ANALYTICAL APPROACH: Cox proportional hazards regression was used to investigate the associations between the time smoking is initiated each day and the risk of CKD. The potential interactions of smoking timing with risk factors in relationship to CKD risk were assessed on both multiplicative and additive scales. RESULTS: During a median follow-up period of 12 years, 940 incident CKD cases occurred. Shorter durations of time from waking to the first cigarette were associated with a higher risk of incident CKD (P trend=0.01). Compared with>120 minutes, the adjusted hazard ratio (HR) associated with smoking timing was 1.28 (95% CI, 0.92-1.80) for 61-120 minutes, 1.48 (95% CI, 1.11-1.96) for 30-60 minutes, 1.36 (95% CI, 1.01-1.88) for 5-15 minutes, and 1.70 (95% CI, 1.22-2.37) for<5 minutes, respectively. Furthermore, there was a significant additive interaction and multiplicative interactions between the timing of smoking and a healthy diet score (P for additive interaction=0.01; P for multiplicative interaction = 0.004). LIMITATIONS: Generalizability, possible residual confounding, limiting causal inference. CONCLUSIONS: These findings reveal a significant association between the shorter time from waking to the first cigarette and a higher CKD risk. The magnitude of these associations was greater in the setting of an unhealthy diet. PLAIN-LANGUAGE SUMMARY: This study explored the association of the daily timing of first cigarette smoking and the occurrence of kidney disease. Further, we addressed whether this association was influenced by the quality of the diet. The study found that smoking very soon after waking, especially when combined with a poorer quality diet, was associated with a significantly increased risk of developing chronic kidney disease. This research emphasizes the value of healthier lifestyle choices for kidney health.

Social Isolation, Loneliness, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes Mellitus.

RATIONALE & OBJECTIVE: Social disconnection has been associated with poor cardiometabolic health. This study sought to investigate the associations of social isolation and loneliness with diabetic microvascular complications (DMCs) among individuals with type 2 diabetes mellitus (T2DM) and compare these associations versus those related to traditional risk factors. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 24,297 UK Biobank participants with T2DM and no DMCs at baseline. EXPOSURE: Social isolation and loneliness were measured using self-reported questionnaires. OUTCOME: The incidence of DMCs defined as a composite of diabetic kidney disease, diabetic retinopathy, or diabetic neuropathy. ANALYTICAL APPROACH: Multivariable cause-specific hazards regression. To compare the relative importance of social disconnection with other established factors, the R2 values of the Cox models were calculated. RESULTS: During a median follow-up of 12.6 years, 5,530 patients were documented to experience DMCs (3,458 with diabetic kidney disease, 2,255 with diabetic retinopathy, and 1,146 with diabetic neuropathy). The highest level of social isolation was associated with an increased risk of any DMC component (most vs least: HR, 1.13; 95% CI, 1.05-1.22), especially diabetic kidney disease (HR, 1.14; 95% CI, 1.04-1.25) and neuropathy (HR, 1.31; 95% CI, 1.11-1.53). Any level of loneliness was associated with an increased risk of any DMC component (HR, 1.12; 95% CI, 1.02-1.23) and diabetic kidney disease (HR, 1.16; 95% CI, 1.03-1.30). Social isolation and loneliness exhibited associations with DMCs comparable to those of other conventional risk factors, including smoking, blood pressure, and physical activity. LIMITATIONS: Limited generalizability related to the composition of participants in the UK Biobank Study. CONCLUSIONS: Social isolation and loneliness were independently associated with a higher risk of incident DMCs among individuals with T2DM, with comparable importance to other traditional risk factors. These findings underscore social isolation and loneliness as novel and potentially modifiable risk factors for DMCs. PLAIN-LANGUAGE SUMMARY: Social isolation and loneliness are important social determinants that are associated with adverse cardiometabolic health. Individuals with diabetes are particularly vulnerable to social isolation and loneliness. However, the relationship of social isolation or loneliness with diabetic microvascular complications (DMCs) remains unclear. Our study used the UK Biobank study data to investigate the associations of social isolation and loneliness with the development of DMCs. We found that social isolation and loneliness were independently associated with a higher risk of incident DMCs. Remarkably, their association with DMCs was comparable to those of other lifestyle factors such as smoking, blood pressure, and physical activity. These findings collectively imply that social isolation and loneliness are 2 important potentially modifiable risk factors for DMCs among individuals with type 2 diabetes mellitus.

Increased microgastropoda sampling give new insights into the phylogenetic relationships of Littorinoidea (Littorinimorpha).

Littorinoidea is one of the most diverse radiations and the most successful group that evolutionary transitions from marine to terrestrial within Littorinimorpha. With such an unmatched diversity, few phylogenetic investigations have attempted to understand their evolutionary relationships, and existing research has primarily focused on typical intertidal species. To address this gap, we conducted the first phylogenomic analysis of the Littorinoidea, leveraging 35 transcriptomes to investigate their internal relationships. Our analyses revealed significant revisions necessary within the Littorinoidea: 1) Pomatias appears distantly related to Littorinidae, suggesting a potential ancestral origin outside of Littorinoidea, challenging traditional classification. The homology of penial innervation within Littorinoidea warrants reevaluation. 2) Lacuna's placement indicates a close relationship with Naticidae, prompting consideration for its removal from Littorinidae. 3) Based on the current phylogenetic research, Peasiella may belong to a distinct family separate from Littorinidae. 4) Our findings support revising the placement of Pteropods within the Littorinimorpha, which is situated phylogenetically between the families Littorinoidea and Naticoidea. Additionally, we highlight the impact of site heterogeneity and evolutionary rate variation on phylogenetic inference. Our study provides a robust phylogenomic framework for the Littorinoidea, emphasizing the importance of including microgastropoda taxa in molecular phylogenetic reconstructions of gastropod subgroups.

1.55 µm wavelength band photonic crystal surface emitting laser with n-side photonic crystal and operation at up to 85 °C.

We describe the structure, fabrication, and measured performance of a 1543 nm wavelength photonic crystal surface emitting laser. An asymmetric double lattice design was used to achieve single mode lasing with side mode suppression ratios >40 dB. The photonic crystal was formed using encapsulated air holes in an n-doped InGaAsP layer with an InGaAlAs active layer then grown above it. In this way a laser with a low series resistance of 0.32 Ω capable of pulsed output powers of 171 mW at 25 °C and 40 mW at 85 °C was demonstrated.

Polarization-insensitive multimode interference coupler on an x-cut thin-film lithium niobate platform.

Thin-film lithium niobate (TFLN) is a promising integrated photonics platform but currently lacks a polarization-insensitive multimode interference (MMI) coupler, a crucial component for polarization-related optical communication applications such as polarization management, polarization-division multiplexing, and polarization-insensitive modulation systems. This paper presents a novel, to the best of our knowledge, approach by rotating the MMI structure on an anisotropic x-cut TFLN at specific angles to compensate for the difference in the beat length between the two polarizations. A polarization-insensitive 1 × 2 MMI coupler is experimentally achieved with measured transmittances of -2.5 to -4 dB for both output ports and polarization modes in the wavelength range of 1520-1580 nm.