The active zone protein Clarinet regulates synaptic sorting of ATG-9 and presynaptic autophagy.

Autophagy is essential for cellular homeostasis and function. In neurons, autophagosome biogenesis is temporally and spatially regulated to occur near presynaptic sites, in part via the trafficking of autophagy transmembrane protein ATG-9. The molecules that regulate autophagy by sorting ATG-9 at synapses remain largely unknown. Here, we conduct forward genetic screens at single synapses of C. elegans neurons and identify a role for the long isoform of the active zone protein Clarinet (CLA-1L) in regulating sorting of autophagy protein ATG-9 at synapses, and presynaptic autophagy. We determine that disrupting CLA-1L results in abnormal accumulation of ATG-9 containing vesicles enriched with clathrin. The ATG-9 phenotype in cla-1(L) mutants is not observed for other synaptic vesicle proteins, suggesting distinct mechanisms that regulate sorting of ATG-9-containing vesicles and synaptic vesicles. Through genetic analyses, we uncover the adaptor protein complexes that genetically interact with CLA-1 in ATG-9 sorting. We also determine that CLA-1L extends from the active zone to the periactive zone and genetically interacts with periactive zone proteins in ATG-9 sorting. Our findings reveal novel roles for active zone proteins in the sorting of ATG-9 and in presynaptic autophagy.

Relationship of serum 25-hydroxyvitamin D, obesity with new-onset obstructive sleep apnea.

OBJECTIVE: The prospective association between vitamin D and obstructive sleep apnea (OSA) remains uncertain. We aimed to assess the association between serum 25-hydroxyvitamin D (25(OH)D), a major circulating form of vitamin D, and new-onset OSA, and examine the modifying effect of obesity. MATERIALS AND METHODS: This prospective cohort study included 444,975 participants from UK Biobank without prior OSA. The primary outcome was new-onset OSA. RESULTS: During a median follow-up duration of 12.0 years, 6051 (1.4%) participants occurred new-onset OSA. Overall, there was an inverse relation of serum 25(OH)D concentrations with the risk of new-onset OSA (per SD increment, HR, 0.92; 95%CI: 0.89-0.95). In the analysis of the interactions of serum 25(OH)D with the combination of BMI (<25, 25- < 30, and ≥30 kg/m2) and waist circumference (WC) (<90 and ≥90 cm) categories on new-onset OSA, the significantly inverse association of serum 25(OH)D and new-onset OSA was mainly found in participants with both BMI ≥ 25 kg/m2 and WC ≥ 90 cm (BMI 25-30 kg/m2 and WC ≥ 90 cm: per SD increment, HR, 0.90; 95%CI: 0.84-0.95; BMI ≥ 30 kg/m2 and WC ≥ 90 cm: per SD increment, HR, 0.85; 95%CI: 0.81-0.88), but not in other four groups with BMI < 25 kg/m2 or WC < 90 cm (P -interaction = 0.004). CONCLUSIONS: There was an inverse relation of serum 25(OH)D with the risk of new-onset OSA in participants with both BMI ≥ 25 kg/m2 and WC ≥ 90 cm. Our findings suggest the importance of maintaining a higher serum 25(OH)D concentration for primary prevention of OSA in a population with obesity.

circ_JMJD1C expedites breast cancer progression by regulating miR-182-5p/JMJD1C/SOX4 axis.

Circular RNAs (circRNAs) are engaged in various types of cancers. This study aimed to investigate the roles of circ_0006743 (circ_JMJD1C) in breast cancer. The downstream of circ_JMJD1C and their interaction network was determined by bioinformatic analyses. Gene expression were analyzed through western blot and qRT-PCR assays. Functional assays were conducted in vitro and in vivo to verify circ_JMJD1C role in BC. FISH and confocal analysis indicated the cellular distribution of circ_JMJD1C. Luciferase reporter, RNA immune-precipitation (RIP) assays, as well as Pearson's correlation analysis, were implemented to test the relation of miR-182-5p, JMJD1C and circ_JMJD1C. Circ_JMJD1C and JMJD1C expression were both elevated, and their expression was positively correlated in BC. Circ_ JMJD1C knockdown hindered BC cell proliferation, invasion, and migration, along with epithelial-mesenchymal transition (EMT) in vitro and in vivo. Circ_JMJD1C facilitated BC progression by the miR-182-5p-JMJD1C axis. Circ_JMJD1C epigenetically upregulated SOX4. Circ_JMJD1C promotes the aggressiveness of BC via regulating miR-182-5p/JMJD1C/SOX4 axis. This may provide a novel and promising therapy targeting BC.

Association between lung function and risk of microvascular diseases in patients with diabetes: A prospective cohort and Mendelian randomization study.

BACKGROUND AND AIMS: To investigate causal relationships of lung function with risks microvascular diseases among participants with diabetes, type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM), respectively, in prospective and Mendelian randomization (MR) study. METHODS AND RESULTS: 14,617 participants with diabetes and without microvascular diseases at baseline from the UK Biobank were included in the prospective analysis. Of these, 13,421 had T2DM and 1196 had T1DM. The linear MR analyses were conducted in the UK Biobank with 6838 cases of microvascular diseases and 10,755 controls. Lung function measurements included forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The study outcome was microvascular diseases, a composite outcome including chronic kidney diseases, retinopathy and peripheral neuropathy. During a median follow-up of 12.1 years, 2668 new-onset microvascular diseases were recorded. FVC (%predicted) was inversely associated with the risk of new-onset microvascular diseases in participants with diabetes (Per SD increment, adjusted HR = 0.86; 95%CI:0.83-0.89), T2DM (Per SD increment, adjusted HR = 0.86; 95%CI:0.82-0.90) and T1DM (Per SD increment, adjusted HR = 0.87; 95%CI: 0.79-0.97), respectively. Similar results were found for FEV1 (%predicted). In MR analyses, genetically predicted FVC (adjusted RR = 0.55, 95%CI:0.39-0.77) and FEV1 (adjusted RR = 0.48, 95%CI:0.28-0.83) were both inversely associated with microvascular diseases in participants with T1DM. No significant association was found in those with T2DM. Similar findings were found for each component of microvascular diseases. CONCLUSION: There was a causal inverse association between lung function and risks of microvascular diseases in participants with T1DM, but not in those with T2DM.

Positive association between dietary manganese intake and new-onset hypertension: A nationwide cohort study in China.

BACKGROUND AND AIM: To date, few studies have investigated the association between dietary manganese intake and the risk of hypertension, so the prospective relationship of dietary manganese intake and new-onset hypertension remains uncertain. We aimed to investigate the association between dietary manganese intake and the risk of new-onset hypertension in the general Chinese population. METHODS AND RESULTS: This prospective cohort study included 12,177 participants who were free of hypertension at baseline from China Health and Nutrition Survey (CHNS). Dietary intake was measured by 3 consecutive 24-h dietary recalls combined with a household food inventory. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or diagnosed by a physician or under antihypertensive treatment during the follow-up. During a median follow-up duration of 6.1 years, 4269 (44.9 per 1000 person-years) participants developed new-onset hypertension. Overall, there was a positive association between dietary manganese intake and new-onset hypertension. The adjusted HRs (95%CIs) of new-onset hypertension were 1.00 (reference), 0.97 (0.87, 1.08), 1.24 (1.10, 1.39) and 1.75 (1.52, 2.01) across the quartiles of dietary manganese intake, respectively. Accordingly, a significantly higher risk of new-onset hypertension (HR, 1.38; 95%CI: 1.27, 1.50) was found in participants in quartiles 3-4 of dietary manganese intake (≥6.0 mg/day), compared with those in quartiles 1-2 (<6.0 mg/day). CONCLUSIONS: In the general Chinese population, dietary manganese intake was positively associated with the risk of new hypertension, independent of sodium intake and other important covariates.

Different sedentary behaviors, genetic susceptibility of hypertension, and new-onset hypertension: Mediating effects of body mass index and grip strength.

BACKGROUND: The association between different sedentary behaviors and hypertension risk remains unclear. We aimed to explore the relationship between different domains of sedentary behaviors and new-onset hypertension, investigate whether genetic susceptibility to hypertension modifies the relationship, and examine the extent to which the relationship is mediated by body mass index (BMI) and grip strength. METHODS: 212 714 participants without baseline hypertension in the UK Biobank were enrolled. The three major sedentary behaviors (TV-watching, nonoccupational computer use, and driving) were measured using touch screen questionnaires. The primary outcome was new-onset hypertension. RESULTS: During a median follow-up of 11.9 years, 13 983 participants developed hypertension. There was a linear positive association between TV-watching time and new-onset hypertension (p for nonlinearity =0.868). A J-shaped association was found for nonoccupational computer use time and driving time with new-onset hypertension, with an inflection point of 0.5 h/day for both (both p for nonlinearity <0.001). Polygenetic risk scores for hypertension (based on 118 related single-nucleotide polymorphisms) did not significantly modify these associations (all p-interactions >0.05). Furthermore, the detrimental effects of long-term sedentary behaviors on hypertension were mediated by BMI by 21%-30%, and the beneficial effects of limited sitting time (within 0.5 h/day) for driving and nonoccupational computer use were mediated by grip strength by 6-25%. CONCLUSIONS: There was a positive association for hands-independence sedentary behavior (TV-watching), and a J-shaped association for hands-dependence sedentary behaviors (nonoccupational computer use and driving) with new-onset hypertension, regardless of genetic risks of hypertension. These relationships were partly mediated by BMI and grip strength.

Periosteal chondroblastoma of the femoral neck: two cases and a review of the literature.

Chondroblastoma is a rare benign cartilaginous tumor mostly confined to the epiphyses and apophyses. Cases outside the epiphyseal region are exceedingly rare. Extramedullary chondroblastomas are exceptional; to our knowledge, only two cases qualified as "periosteal chondroblastoma" have been described in the literature. We report two cases of metaphyseal periosteal chondroblastoma both located on the inferior surface of the femoral neck. Both cases were paucicellular with an unusual dense sclerotic reaction. The diagnosis of chondroblastoma was supported by the expression of histone 3.3, K36M mutant in tumor cells.

Association of accelerometer-measured physical activity and its change with progression to chronic kidney disease in adults with type 2 diabetes and overweight/obesity.

OBJECTIVE: To examine the long-term association of objectively measured moderate-to-vigorous physical activity (MVPA) and its longitudinal changes with progression to chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) and overweight/obesity. METHODS: This study included 1746 participants in the Look AHEAD trial with baseline estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2. MVPA was measured at baseline, year 1, year 4 and year 8 using an RT3 accelerometer. The outcome was progression to CKD, defined as eGFR<60 mL/min per 1.73 m2 with a drop of ≥30% or end-stage kidney disease. Cox hazards models were fitted to examine the association between MVPA and outcomes. RESULTS: Over a median follow-up of 12.0 years, 567 participants experienced progression to CKD. Overall, there was a linear inverse association of cumulative average total MVPA (per 100 min/week higher amount, HR: 0.91; 95% CI: 0.86 to 0.96) and MVPA accumulated in bouts of ≥10 min (per 100 minutes/week higher amount, HR: 0.81; 95% CI: 0.72 to 0.91) with progression to CKD. Moreover, an increase in total MVPA from baseline to year 4 (the fourth quartile, ≥63.2 min/week) was associated with a 33% lower risk of progression to CKD compared with the largest MVPA reduction (the first quartile, <-198.3 min/week). A lower risk of progression to CKD was also observed for increases in MVPA accumulated in bouts of both <10 min and ≥10 min. CONCLUSIONS: Longer MVPA time and increases in MVPA was associated with a reduced risk of progression to CKD in adults with overweight/obesity and T2D.

Variety and quantity of dietary insoluble fiber intake from different sources and risk of new-onset hypertension.

BACKGROUND: The relations of the variety and quantity of different sources of dietary insoluble fibers and hypertension remain uncertain. We aimed to investigate the associations between the variety and quantity of insoluble fibers intake from six major food sources and new-onset hypertension, using data from the China Health and Nutrition Survey (CHNS). METHODS: Twelve thousand one hundred thirty-one participants without hypertension at baseline from CHNS were included. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. The variety score of insoluble fiber sources was defined as the number of insoluble fiber sources consumed at the appropriate level, accounting for both types and quantities of insoluble fibers. The study outcome was new-onset hypertension, defined as blood pressure ≥ 140/90 mmHg, or physician-diagnosed hypertension or receiving antihypertensive treatments during the follow-up. RESULTS: During a median follow-up of 6.1 years, 4252 participants developed hypertension. There were L-shaped associations of dietary insoluble fibers derived from vegetables, beans, tubers, and fruits with new-onset hypertension; a reversed J-shaped association of whole grain-derived insoluble fiber with new-onset hypertension; and no obvious association of refined grain-derived insoluble fiber with new-onset hypertension. Therefore, refined grain was not included in the insoluble fiber variety score calculation. More importantly, a higher insoluble fiber variety score was significantly associated with lower risks of new-onset hypertension (per score increment, hazard ratio, 0.50; 95% CI, 0.45-0.55). CONCLUSIONS: There was an inverse association between the variety of insoluble fibers with appropriate quantity from different food sources and new-onset hypertension.

A U-shaped association between dietary phosphorus intake and new-onset hypertension: a nationwide cohort study in China.

BACKGROUND: The association between dietary phosphorus intake and the risk of hypertension remains uncertain. We aimed to investigate the relation of dietary phosphorus intake with new-onset hypertension among Chinese adults. METHODS: A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey (CHNS) were included. Dietary intake was measured by 3 consecutive 24-hour dietary recalls combined with a household food inventory. New-onset hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or diagnosed by a physician or under antihypertensive treatment during the follow-up. RESULTS: During a median follow-up of 6.1 years, 4,269 participants developed new-onset hypertension. Overall, the association between dietary phosphorus intake and new-onset hypertension followed a U-shape (P for nonlinearity<.001). Consistently, when dietary phosphorus intake was assessed as quintiles, compared with those in the 3rd to 4th quintiles (912.0-<1089.5 mg/d), a significantly higher risk of new-onset hypertension was found in participants in the 1st to 2nd quintiles (<912.0 mg/d: HR, 1.23; 95% CI, 1.14-1.33), and the fifth quintile (≥1089.5 mg/d: HR, 1.21; 95% CI, 1.10-1.33). CONCLUSION: There was a U-shaped association between dietary phosphorus intake and new-onset hypertension in general Chinese adults.

Association of serum uric acid with all-cause and cardiovascular mortality among adults with nonalcoholic fatty liver disease.

AIM: The association between serum uric acid (SUA) and mortality from cardiovascular diseases (CVDs) in nonalcoholic fatty liver disease (NAFLD) participants remains uncertain. We aim to investigate the relations of SUA with the risk of CVD mortality among adults with and without NAFLD. METHODS: Using data from National Health and Nutrition Examination Survey (NHANES) 1999-2014, a total of 17,858 participants were recruited. Of these, 5767 had a US Fatty Liver Index (USFLI) ≥30 and were classified as having NAFLD. Death information was obtained from the National Death Index until 2015. RESULTS: During a mean follow-up of 8.3 years, 427 participants died from CVD. Overall, there was a positive association between SUA and CVD mortality among participants with NAFLD (per SD µmol/L increment, adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.16-1.68). Accordingly, among those with NAFLD, when SUA was assessed as quartiles, compared with those in the first quartile, a significantly higher risk of CVD mortality was found in participants in the fourth quartile (adjusted HR, 2.69; 95% CI, 1.51-4.80). However, there was no significant association between SUA and CVD mortality among participants without NAFLD (per SD µmol/L increment, adjusted HR, 1.01; 95% CI, 0.83-1.22). Similar trends were found for all-cause mortality. Similar results were also found when using FLI ≥ 60 to define NAFLD. CONCLUSIONS: In a large and nationally representative sample of US adults, a higher SUA was significantly associated with a higher risk of CVD mortality among participants with NAFLD, but not in those without NAFLD.

Associations between visceral adiposity index and incident nephropathy outcomes in diabetic patients: Insights from the ACCORD trial.

AIMS: Visceral adiposity index (VAI) was a reliable marker for visceral adiposity accumulation and dysfunction. The association between VAI and nephropathy outcomes remains uncertain in patients with type 2 diabetes (T2DM). We aimed to evaluate the longitudinal relationships between VAI and incident nephropathy outcomes in T2DM patients. MATERIALS AND METHODS: Ten thousand one hundred and thirty two participants with T2DM from the ACCORD trial were included in the present study. Cumulative average VAI based on VAI measurements at baseline and follow-up was used to represent long-term VAI status. The primary outcome was the incident composite nephropathy outcome defined as: (1) serum creatinine doubling or >20 ml/min decrease in eGFR; or (2) development of macro-albuminuria; or (3) renal failure or end stage kidney disease (dialysis) or serum creatinine >3.3 mg/dl. RESULTS: During 26,168 person-years follow-up duration, 6094 (60.1%) participants developed the incident composite nephropathy outcome. When assessing cumulative average VAI as quartiles, compared with those in the 1-2 quartiles (<2.6), a significantly higher risk of incident composite nephropathy outcomes was observed among participants in the 3-4 quartiles (≥2.6, adjusted HR: 1.09, 95% CI: 1.01, 1.18). Moreover, the positive association was consistent in participants with or without single abnormal VAI components, including general obesity, abdominal obesity, elevated triglycerides, and low high-density lipoprotein cholesterol, or with different numbers of abnormal VAI components. Additionally, the positive association was stronger in participants with cumulative average systolic blood pressure <130 mmHg (vs. ≥130 mmHg; p-interaction < 0.001). CONCLUSIONS: In T2DM patients, higher cumulative average VAI was associated with a higher risk of incident composite nephropathy outcomes. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier: NCT00000620.

Associations between Serum 25-hydroxyvitamin D, Sun Exposure Time, Dietary Vitamin D Intake, and New-Onset Acute Kidney Injury among 413,169 UK Adults.

BACKGROUND: The prospective associations of serum 25(OH)D, sun exposure time, and dietary vitamin D with risk of acute kidney injury (AKI) are unclear. OBJECTIVES: We aimed to evaluate the relations of serum 25(OH)D, sun exposure time, and dietary vitamin D intake with new-onset AKI and examine whether genetic susceptibility modified such associations. METHODS: A total of 413,169 participants (mean age was 56.4 y, 47.2% were male) from UK Biobank without prior AKI were included. Sun exposure time was expressed as time spent outdoors. Genetic risk scores were calculated by 263 single nucleotide polymorphisms, which showed significant associations with the estimated glomerular filtration rate. The primary outcome was new-onset AKI. Cox proportional hazards models were used to estimate the HRs and (95% CIs). RESULTS: During a median follow-up duration of 12 y, 16,938 (4.1%) participates developed new-onset AKI. Compared with those with serum 25(OH)D <25 nmol/L, significantly lower risks of new-onset AKI were found between participants with 25(OH)D 25 to <50 nmol/L (adjusted HR: 0.76; 95% CI: 0.73, 0.80), and ≥50 nmol/L (adjusted HR: 0.69; 95% CI: 0.65, 0.72). Moreover, in summer, participants who spent ≥4 h outdoors per day (tertile 3) had a significantly lower risk of new-onset AKI (adjusted HR: 0.90; 95% CI: 0.86, 0.95) than those who spent <2 h outdoors per day (tertile 1). Similar results were found for time spent outdoors in winter. In addition, those in quintile 5 of dietary vitamin D intake showed a lower risk of new-onset AKI (≥4.2 µg/d, adjusted HR: 0.90; 95% CI: 0.82, 0.98) than those in quintile 1 (<1.0 µg/d). Genetic risks of kidney diseases did not significantly modify all the 3 above associations (all P-interactions >0.05). CONCLUSIONS: Serum 25(OH)D concentrations, time spent outdoors, and dietary vitamin D intake were all inversely associated with new-onset AKI, independent of genetic risks for kidney diseases.

Inverse association of glucosamine use and risk of new-onset kidney stones in UK adults with less sedentary time.

OBJECTIVE: To assess the association of different sedentary behaviors and glucosamine use with the risk of kidney stones and examine the modification of genetic risk of kidney stones on this association. METHODS: 473,225 participants free of kidney stones at baseline from the UK Biobank were included. Total sedentary time was calculated as the sum of the duration of TV-watching, driving, and non-occupational computer using. The primary outcome was new-onset kidney stones. RESULTS: During a median follow-up of 12.0 years, 5528 cases of kidney stones were documented. All major sedentary behaviors and total sedentary time were significantly positively related to the risk of kidney stones (All P for trend<0.05). Participants with total sedentary time ≥ 3.5 h/day had a significantly higher risk of new-onset kidney stones (vs. <3.5 h/day [tertile 1]; HR, 1.18; 95%CI,1.10-1.27). Compared with non-users, participants who regularly used glucosamine had a significantly lower risk of new-onset kidney stones in those with total sedentary time < 3.5 h/day (HR, 0.72; 95%CI,0.59-0.86), but not in those with total sedentary time ≥ 3.5 h/day (HR, 0.99; 95%CI,0.91-1.08; P-interaction = 0.001). Among participants with total sedentary time < 3.5 h/day, there was a dose-response relationship of glucosamine use with new-onset kidney stones (P for trend<0.001). Genetic risks of kidney stones did not significantly modify the association. CONCLUSIONS: TV-watching, driving and non-occupational computer using were all positively associated with the risk of new-onset kidney stones. Glucosamine use was associated with a lower risk of new-onset kidney stones in participants with total sedentary time < 3.5 h/day, following a dose-response relationship.

J-shaped association between dietary copper intake and all-cause mortality: a prospective cohort study in Chinese adults.

The association between dietary Cu intake and mortality risk remains uncertain. We aimed to investigate the relationship of dietary Cu intake with all-cause mortality among Chinese adults. A total of 17 310 participants from the China Health and Nutrition Survey, a national ongoing open cohort of Chinese participants, were included in the analysis. Dietary intake was measured by three consecutive 24-h dietary recalls in combination with a weighing inventory over the same 3 d. The average intakes of the 3-d dietary macronutrients and micronutrients were calculated. The study outcome was all-cause mortality. During a median follow-up of 9·0 years, 1324 (7·6 %) participants died. After adjusting for sex, age, BMI, ever alcohol drinking, ever smoking, education levels, occupations, urban or rural residents, systolic blood pressure, diastolic blood pressure and the intakes of fat, protein and carbohydrate, the association between dietary Cu intake and all-cause mortality followed a J-shape (Pfor nonlinearity = 0·047). When dietary Cu intake was assessed as quartiles, compared with those in the first quartile (<1·60 mg/d), the adjusted hazard ratios for all-cause mortality were 0·87 (95 % CI (0·71, 1·07)), 0·98 (95 % CI (0·79, 1·21)) and 1·49 (95 % CI (1·19, 1·86)), respectively, in participants in the second (1·60-<1·83 mg/d), third (1·83-<2·09 mg/d) and fourth (≥2·09 mg/d) quartiles. A series of subgroup analyses and sensitivity analyses showed similar results. Overall, our findings emphasised the importance of maintaining optimal dietary Cu intake levels for prevention of premature death.

A U-shaped association between dietary phosphorus intake and new-onset diabetes: A nationwide cohort study in China.

BACKGROUND AND AIMS: The association between dietary phosphorus intake and the risk of diabetes remains uncertain. We aimed to investigate the relation of dietary phosphorus intake with new-onset diabetes among Chinese adults. METHODS AND RESULTS: A total of 16,272 participants who were free of diabetes at baseline from the China Health and Nutrition Survey were included. Dietary intake was measured by 3 consecutive 24-h dietary recalls combined with a household food inventory. Participants with self-reported physician-diagnosed diabetes, or fasting glucose ≥7.0 mmol/L or glycated hemoglobin ≥6.5% during the follow-up were defined as having new-onset diabetes. During a median follow-up of 9.0years, 1101 participants developed new-onset diabetes. Overall, the association between dietary phosphorus intake with new-onset diabetes followed a U-shape (P for nonlinearity<0.001). The risk of new-onset diabetes significantly decreased with the increment of dietary phosphorus intake (per SD increment: HR, 0.64; 95%CI, 0.48-0.84) in participants with phosphorus intake <921.6 mg/day, and increased with the increment of dietary phosphorus intake (per SD increment: HR, 1.33; 95%CI, 1.16-1.53) in participants with phosphorus intake ≥921.6 mg/day. Consistently, when dietary phosphorus intake was assessed as quintiles, compared with those in the 3rd quintile (905.0-<975.4 mg/day), significantly higher risks of new-onset diabetes were found in participants in the 1st-2nd quintiles (<905.0 mg/day: HR, 1.59; 95%CI, 1.30-1.94), and 4th-5th quintiles (≥975.4 mg/day: HR, 1.46; 95%CI, 1.19-1.78). CONCLUSIONS: There was a U-shaped association between dietary phosphorus intake and new-onset diabetes in general Chinese adults, with an inflection point at 921.6 mg/day and a minimal risk at 905.0-975.4 mg/day of dietary phosphorus intake.

Compact plasmon modulator based on the spatial control of carrier density in indium tin oxide.

To keep pace with the demands of semiconductor integration technology, a semiconductor device should offer a small footprint. Here, we demonstrate a compact electro-optic modulator by controlling the spatial distribution of carrier density in indium tin oxide (ITO). The proposed structure is mainly composed of a symmetrical metal electrode layer, calcium fluoride dielectric layer, and an ITO propagating layer. The carrier density on the surface of the ITO exhibits a periodical distribution when the voltage is applied on the electrode, which greatly enhances the interaction between the surface plasmon polaritons (SPPs) and the ITO. This structure can not only effectively improve the modulation depth of the modulator, but also can further reduce the device size. The numerical results indicate that when the length, width, and height of the device are 14 µm, 5 µm, and 8 µm, respectively, the modulation depth can reach 37.1 dB at a wavelength of 3.66 µm. The structure can realize a broadband modulation in theory only if we select a different period of the electrode corresponding to the propagating wavelength of SPPs because the modulator is based on the scattering effect principle. This structure could potentially have high applicability for optoelectronic integration, optical communications, and optical sensors in the future.

Combined handgrip strength and walking pace, genetic susceptibility, and incident hypertension: A prospective study in UK Biobank.

INTRODUCTION: We aimed to investigate the relations of handgrip strength, walking pace and the combination of handgrip strength and walking pace with incident hypertension, and to explore whether this association was modified by the genetic risk of hypertension. METHODS: 214 214 participants without prior hypertension in the UK Biobank were included. Handgrip strength was assessed by dynamometer. Walking pace was self-defined as slow, average, or brisk. The study outcome was incident hypertension. A genetic risk score for hypertension was generated using a Bayesian approach applied to meta-analyzed summary statistics GWAS data. RESULTS: Over a median follow-up of 11.9 years, 13 344 (6.2%) participants developed incident hypertension. When handgrip strength was assessed as sex-specific quartiles, compared with those with the lowest handgrip strength (quartile 1), the adjusted HRs (95% CI) of incident hypertension in quartile 2, quartile 3, and quartile 4 were 0.80 (0.69, 0.93), 0.74 (0.64, 0.86), and 0.72 (0.61, 0.84), respectively. Compared with those with slow walking pace, participants with average (HR, 0.52; 95% CI: 0.40, 0.67) or brisk (HR, 0.43; 95% CI: 0.32, 0.56) walking pace had significantly lower risks of hypertension. Moreover, compared with those with both lower handgrip strength (quartile 1) and slow walking pace, the lowest risk of incident hypertension was observed in participants with both high handgrip strength (quartiles 2-4) and fast (average or brisk) walking pace (HR, 0.36; 95% CI: 0.25, 0.52). Genetic risks of hypertension did not significantly modify the association (p-interaction = 0.300). CONCLUSION: Both higher handgrip strength and faster walking pace were significantly associated with a lower risk of incident hypertension, independent of genetic risks of hypertension.

Echocardiographic measurements of left ventricular dimensions and function in newborns with omphalocele and pulmonary.

PURPOSE: The purpose of this study was to explore echocardiographic parameters of the left ventricle (LV) in relation to the outcomes of omphalocele neonates with pulmonary hypertension (PH). METHODS: This retrospective study was conducted among omphalocele patients with PH born from 2019 to 2020. Patients in this study did not have additional severe malformations or chromosomal aberrations. Patients who died under palliative care were excluded. The echocardiographic parameters of LV were obtained within 24 h after birth. Clinical and outcomes data were recorded, echocardiograms evaluated for left ventricular internal dimension in end-diastole (LVIDd), end-diastolic volume (EDV), stroke volume (SV) and cardiac output index (CI), among others. RESULTS: There were 18 omphalocele newborns with PH, of whom 14 survived and 4 died. Both groups were comparable in the baseline characteristics. Non-survival was associated with a smaller LV [LVIDd (12.2 mm versus15.7 mm, p < 0.05), EDV (3.5 ml versus 6.8 ml, p < 0.05)] and with worse systolic function [SV (2.3 ml versus 4.2 ml, p < 0.05), and CI (1.7 L/min/m2 versus 2.9 L/min/m2, p < 0.01)]. CONCLUSION: In the cohort of omphalocele patients with PH, lower LVIDd, EDV, SV and CI were associated with mortality. LEVEL OF EVIDENCE: Level III.

Residential green and blue spaces with nonalcoholic fatty liver disease incidence: Mediating effect of air pollutants.

BACKGROUND: This study aimed to investigate the relationship of residential green and blue spaces with incident nonalcoholic fatty liver disease (NAFLD), and explore the potential mediation effects of air pollutants and modification effect of genetic susceptibility. METHODS: 411,200 UK Biobank participants without prior liver diseases were included. Land use data were used to estimate residential green and blue spaces (land coverage percentage) at 300 m and 1000 m buffer. The study outcome was incident NAFLD, ascertained through linkage to hospital admissions and death registry records. RESULTS: 5198 NAFLD cases were documented after a median follow-up of 12.5 years. Green and blue spaces were inversely associated with the hazard of NAFLD: per standard deviation (SD) increment of green space coverage at 300 m (SD: 14.5 %; HR, 0.88, 95 %CI, 0.86-0.91) and 1000 m (SD: 14.1 %; HR, 0.88, 95 %CI, 0.86-0.91) buffer, and blue space coverage at 300 m (SD: 1.0 %; HR,0.95, 95 %CI, 0.93-0.98) and 1000 m (SD: 1.2 %; HR,0.96, 95 %CI, 0.93-0.99) buffer were related with a 4-12 % reduction of NAFLD incidence. The beneficial effects of approximately 25-52 % of green space exposure and about 5-35 % of blue space exposure on NAFLD incidence were mediated by the reduction of PM2.5, NO2 and NOx (All Pindirect effect <0.05). Moreover, genetic susceptibility of NAFLD did not modify the relationship of green and blue spaces with NAFLD incidence. CONCLUSION: Residential green and blue spaces were inversely related to NAFLD incidence. These results suggest that green and blue spaces are modifiable factors that may help prevent NAFLD, and therefore, can be considered as a novel environmental strategy to promote liver health at the community level, rather than only at the individual level.