High-performance flexible photodetectors based on CdTe/MoS2 heterojunction.

Flexible photodetectors have attracted escalating attention due to their pivotal role in next-generation wearable optoelectronic devices. This work presents high-performance photodetector devices based on CdTe/MoS2 heterojunctions, showcasing outstanding photodetecting and distinctive mechanical properties. The MoS2 film was exfoliated from bulk layered MoS2 and covered by a sputtered ultrathin CdTe film (∼8.4 nm) to form a heterojunction. Benefitting from the photovoltaic effect induced by the built-in electrical field near the high-quality interface, the fabricated CdTe/MoS2 heterojunction photodetector can operate as a self-powered photodetector without any external bias voltage, especially showing a high photodetectivity of 5.84 × 1011 Jones, remarkable photoresponsivity of 270.3 mA W-1, fast photoresponse with a rise/fall time of ∼44.8/134.2 µs and excellent bending durability. These results demonstrate that the CdTe/MoS2 heterojunctions could have significant potential for future applications in optoelectronic devices.

Mtnr1b deletion disrupts placental angiogenesis through the VEGF signaling pathway leading to fetal growth restriction.

The placenta, as a "transit station" between mother and fetus, has functions delivering nutrients, excreting metabolic wastes and secreting hormones. A healthy placenta is essential for fetal growth and development while the melatonergic system seems to play a critical physiological role in this organ since melatonin, its synthetic enzymes and receptors are present in the placenta. In current study, Mtnr1a and Mtnr1b knockout mice were constructed to explore the potential roles of melatonergic system played on the placental function and intrauterine growth retardation (IUGR). The result showed that Mtnr1a knockout had little effect on placental function while Mtnr1b knockout reduced placental efficiency and increased IUGR. Considering the extremely high incidence of IURG in sows, the pregnant sows were treated with melatonin. This treatment reduced the incidence of IUGR. All the evidence suggests that the intact melatonergic system in placenta is required for its function. Mechanistical studies uncovered that Mtnr1b knockout increased placental oxidative stress and apoptosis but reduced the angiogenesis. The RNA sequencing combined with histochemistry study identified the reduced angiogenesis and placental vascular density in Mtnr1b knockout mice. These alterations were mediated by the disrupted STAT3/VEGFR2/PI3K/AKT pathway, i.e., Mtnr1b knockout reduced the phosphorylation of STAT3 which is the promotor of VEGFR2. The downregulated VEGFR2 and its downstream elements of PI3K and AKT expressions, then, jeopardizes the angiogenesis and placental development.

MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.

Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F0 and F1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F0 and F1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.

A Dual-Functional Integration of Photodetectors and Artificial Optoelectronic Synapses on a VO2/WO3 Heterojunction Device.

Bionic visual systems require multimodal integration of eye-like photodetectors and brain-like image memory. However, the integration of photodetectors (PDs) and artificial optoelectronic synapses devices (OESDs) by one device remains a giant challenge due to their photoresponse discrepancy. Herein, a dual-functional integration of PDs and OESDs based on VO2/WO3 heterojunctions is presented. The device can be able to realize a dual-mode conversion between PDs and OESDs through tuning the bias voltage. Under zero bias voltage, the device exhibiting excellent photodetecting behaviors based on the photovoltaic effect, showing a high self-powered photoresponsivity of 18.5 mA W-1 and high detectivity of 7.5 × 1010 Jones with fast photoresponse. When the external bias voltages are applied, it can be acted as an OESD and exhibit versatile electrical and photonic synaptic characteristics based on the trapping and detrapping effects, including synaptic plasticity and learning-experience behaviors. More importantly, benefiting from the excellent photosensing ability and transporting properties, the device shows ultralow-power consumption of 39.0 pJ and a 4 × 4 OESDs array is developed to realize the visual perception and memory. This work not only supplies a novel route to realize complex functional integration just in one device, but also offers effective strategies for developing neuromorphic visual system.

Effects of Prepartum L-Tryptophan Supplementation on the Postpartum Performance of Holstein Cows.

The negative energy balance occurring in the periparturient period of cows will impede their health and postpartum performance. To target this issue, L-tryptophan was supplied to the prepartum cows. The results showed that L-tryptophan supplementation significantly increased the serum melatonin level and was accompanied with increases in SOD activity, IL-10 and colostrum IgA levels as well as decreases in MDA and IL-6 levels compared to the control cows. The incidence of postpartum diseases was significantly lower and the pregnancy rate was significantly higher in cows fed L-tryptophan than in the control group. A striking observation was that prepartum L-tryptophan supplementation not only improved the milk production but also the quality compared to the control cows. In general, supplementation with L-tryptophan in the prepartum period can improve the postpartum reproduction and lactation performance of cows to some extent.

Mode-Locked Operation of High-Order Transverse Modes in a Vertical-External-Cavity Surface-Emitting Laser.

Understanding the mechanism of mode-locking in a laser with high-order transverse mode is important for achieving an ultrashort pulses train under more complicated conditions. So far, mode-locking with high-order transverse mode has not been reported in other lasers except the multimode fiber laser. This paper demonstrates robust mode-locking with high-order transverse mode in a Kerr-lens mode-locked vertical-external-cavity surface-emitting laser for the first time, to the best of our knowledge. While the longitudinal modes are locked, continuous mode-locking accompanied by high-order transverse mode up to TEM40 is observed. The threshold of the mode-locking is only a little bigger than that of the lasing. After the laser oscillation is built up, the mode-locked pulse train can be obtained almost immediately and maintained until the thermal rollover of the laser. Output powers of 717 mW under fundamental mode and 666 mW under high-order transverse mode are achieved with a 4.3 ps pulse duration and 1.1 GHz pulses repetition rate, and some phenomenological explanations to the related characteristics of the mode-locked operation of high-order transverse mode in the vertical-external-cavity surface-emitting laser are proposed.

A prospective cohort study of exposure to household pesticide with cardiovascular diseases mortality in older adults.

OBJECTIVES: We examined the associations of self-reported exposures, and urinary metabolites related to household pesticide with cardiovascular disease (CVD) mortality in older adults based on the 2007 to 2014 waves of National Health and Nutrition Examination Survey (NHANES). METHODS: Information on application and urinary metabolites related to household pesticide exposure were collected. We estimated the risks of household pesticide exposure, urinary metabolites with subsequent incident CVD death using Cox proportional hazards regression models. The indirect effects of urinary metabolites and effect modifications were examined. RESULTS: The participants who reported exposure to household pesticide had a higher risk of incident CVD death (adjusted HR 1.40, 95% CI 1.08 to 1.81). Per 1-log10 increase in urinary N, N-diethyl-3-methylbenzamide (DEET) related to household insect repellents was associated with a higher risk of incident CVD death (adjusted HR 1.97, 95% CI 1.14 to 3.40). Urinary DEET explained 4.21% of the total association between household pesticide exposure and CVD death risk. The participants who persisted a low level of health diet exhibited pronounced CVD death risks with household pesticide exposures. CONCLUSIONS: Exposure to household pesticide, especially household insect repellents, was consistently associated with an elevated CVD death risk in older adults. A heatlhy diet could partly attenuate the associations.

Phenotypic and genetic effect of carotid intima-media thickness on the risk of stroke.

While carotid intima-media thickness (cIMT) as a noninvasive surrogate measure of atherosclerosis is widely considered a risk factor for stroke, the intrinsic link underlying cIMT and stroke has not been fully understood. We aimed to evaluate the clinical value of cIMT in stroke through the investigation of phenotypic and genetic relationships between cIMT and stroke. We evaluated phenotypic associations using observational data from UK Biobank (N = 21,526). We then investigated genetic relationships leveraging genomic data conducted in predominantly European ancestry for cIMT (N = 45,185) and any stroke (AS, Ncase/Ncontrol=40,585/406,111). Observational analyses suggested an increased hazard of stroke per one standard deviation increase in cIMT (cIMTmax-AS: hazard ratio (HR) = 1.39, 95%CI = 1.09-1.79; cIMTmean-AS: HR = 1.39, 95%CI = 1.09-1.78; cIMTmin-AS: HR = 1.32, 95%CI = 1.04-1.68). A positive global genetic correlation was observed (cIMTmax-AS: [Formula: see text]=0.23, P=9.44 × 10-5; cIMTmean-AS: [Formula: see text]=0.21, P=3.00 × 10-4; cIMTmin-AS: [Formula: see text]=0.16, P=6.30 × 10-3). This was further substantiated by five shared independent loci and 15 shared expression-trait associations. Mendelian randomization analyses suggested no causal effect of cIMT on stroke (cIMTmax-AS: odds ratio (OR)=1.12, 95%CI=0.97-1.28; cIMTmean-AS: OR=1.09, 95%CI=0.93-1.26; cIMTmin-AS: OR=1.03, 95%CI = 0.90-1.17). A putative association was observed for genetically predicted stroke on cIMT (AS-cIMTmax: beta=0.07, 95%CI = 0.01-0.13; AS-cIMTmean: beta=0.08, 95%CI = 0.01-0.15; AS-cIMTmin: beta = 0.08, 95%CI = 0.01-0.16) in the reverse direction MR, which attenuated to non-significant in sensitivity analysis. Our work does not find evidence supporting causal associations between cIMT and stroke. The pronounced cIMT-stroke association is intrinsic, and mostly attributed to shared genetic components. The clinical value of cIMT as a surrogate marker for stroke risk in the general population is likely limited.

VO2 /MoO3 Heterojunctions Artificial Optoelectronic Synapse Devices for Near-Infrared Optical Communication.

Artificial optoelectronic synapses (OES) have attracted extensive attention in brain-inspired information processing and neuromorphic computing. However, OES at near-infrared wavelengths have rarely been reported, seriously limiting the application in modern optical communication. Herein, high-performance near-infrared OES devices based on VO2 /MoO3 heterojunctions are presented. The textured MoO3 films are deposited on the sputtered VO2 film by using the glancing-angle deposition technique to form a heterojunction device. Through tuning the oxygen defects in the VO2 film, the fabricated VO2 /MoO3 heterojunction exhibits versatile electrical synaptic functions. Benefiting from the highly efficient light harvesting and the unique interface effect, the photonic synaptic characteristics, mainly including the short/long-term plasticity and learning experience behavior are successfully realized at the O (1342 nm) and C (1550 nm) optical communication wavebands. Moreover, a single OES device can output messages accurately by converting light signals of the Morse code to distinct synaptic currents. More importantly, a 3 × 3 artificial OES array is constructed to demonstrate the impressive image perceiving and learning capabilities. This work not only indicates the feasibility of defect and interface engineering in modulating the synaptic plasticity of OES devices, but also provides effective strategies to develop advanced artificial neuromorphic visual systems for next-generation optical communication systems.

The effect of trisomic chromosomes on spatial genome organization and global transcription in embryonic stem cells.

Aneuploidy frequently occurs in cancer and developmental diseases such as Down syndrome, with its functional consequences implicated in dosage effects on gene expression and global perturbation of stress response and cell proliferation pathways. However, how aneuploidy affects spatial genome organization remains less understood. In this study, we addressed this question by utilizing the previously established isogenic wild-type (WT) and trisomic mouse embryonic stem cells (mESCs). We employed a combination of Hi-C, RNA-seq, chromosome painting and nascent RNA imaging technologies to compare the spatial genome structures and gene transcription among these cells. We found that trisomy has little effect on spatial genome organization at the level of A/B compartment or topologically associating domain (TAD). Inter-chromosomal interactions are associated with chromosome regions with high gene density, active histone modifications and high transcription levels, which are confirmed by imaging. Imaging also revealed contracted chromosome volume and weakened transcriptional activity for trisomic chromosomes, suggesting potential implications for the transcriptional output of these chromosomes. Our data resources and findings may contribute to a better understanding of the consequences of aneuploidy from the angle of spatial genome organization.

Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses.

BACKGROUND: The incidence of prostate cancer is increasing in older males globally. Age, ethnicity, and family history are identified as the well-known risk factors for prostate cancer, but few modifiable factors have been firmly established. The objective of this study was to identify and evaluate various factors modifying the risk of prostate cancer reported in meta-analyses of prospective observational studies and mendelian randomization (MR) analyses. METHODS AND FINDINGS: We searched PubMed, Embase, and Web of Science from the inception to January 10, 2022, updated on September 9, 2023, to identify meta-analyses and MR studies on prostate cancer. Eligibility criteria for meta-analyses were (1) meta-analyses including prospective observational studies or studies that declared outcome-free at baseline; (2) evaluating the factors of any category associated with prostate cancer incidence; and (3) providing effect estimates for further data synthesis. Similar criteria were applied to MR studies. Meta-analysis was repeated using the random-effects inverse-variance model with DerSimonian-Laird method. Quality assessment was then conducted for included meta-analyses using AMSTAR-2 tool and for MR studies using STROBE-MR and assumption evaluation. Subsequent evidence grading criteria for significant associations in meta-analyses contained sample size, P values and 95% confidence intervals, 95% prediction intervals, heterogeneity, and publication bias, assigning 4 evidence grades (convincing, highly suggestive, suggestive, or weak). Significant associations in MR studies were graded as robust, probable, suggestive, or insufficient considering P values and concordance of effect directions. Finally, 92 selected from 411 meta-analyses and 64 selected from 118 MR studies were included after excluding the overlapping and outdated studies which were published earlier and contained fewer participants or fewer instrument variables for the same exposure. In total, 123 observational associations (45 significant and 78 null) and 145 causal associations (55 significant and 90 null) were categorized into lifestyle; diet and nutrition; anthropometric indices; biomarkers; clinical variables, diseases, and treatments; and environmental factors. Concerning evidence grading on significant associations, there were 5 highly suggestive, 36 suggestive, and 4 weak associations in meta-analyses, and 10 robust, 24 probable, 4 suggestive, and 17 insufficient causal associations in MR studies. Twenty-six overlapping factors between meta-analyses and MR studies were identified, with consistent significant effects found for physical activity (PA) (occupational PA in meta: OR = 0.87, 95% CI: 0.80, 0.94; accelerator-measured PA in MR: OR = 0.49, 95% CI: 0.33, 0.72), height (meta: OR = 1.09, 95% CI: 1.06, 1.12; MR: OR = 1.07, 95% CI: 1.01, 1.15, for aggressive prostate cancer), and smoking (current smoking in meta: OR = 0.74, 95% CI: 0.68, 0.80; smoking initiation in MR: OR = 0.91, 95% CI: 0.86, 0.97). Methodological limitation is that the evidence grading criteria could be expanded by considering more indices. CONCLUSIONS: In this large-scale study, we summarized the associations of various factors with prostate cancer risk and provided comparisons between observational associations by meta-analysis and genetically estimated causality by MR analyses. In the absence of convincing overlapping evidence based on the existing literature, no robust associations were identified, but some effects were observed for height, physical activity, and smoking.

Independent association of general and central adiposity with risk of gallstone disease: observational and genetic analyses.

Background: General obesity is a well-established risk factor for gallstone disease (GSD), but whether central obesity contributes additional independent risk remains controversial. We aimed to comprehensively clarify the effect of body fat distribution on GSD. Methods: We first investigated the observational association of central adiposity, characterized by waist-to-hip ratio (WHR), with GSD risk using data from UK Biobank (N=472,050). We then explored the genetic relationship using summary statistics from the largest genome-wide association study of GSD (ncase=43,639, ncontrol=506,798) as well as WHR, with and without adjusting for body mass index (BMI) (WHR: n=697,734; WHRadjBMI: n=694,649). Results: Observational analysis demonstrated an increased risk of GSD with one unit increase in WHR (HR=1.18, 95%CI=1.14-1.21). A positive WHR-GSD genetic correlation (rg =0.41, P=1.42×10-52) was observed, driven by yet independent of BMI (WHRadjBMI: rg =0.19, P=6.89×10-16). Cross-trait meta-analysis identified four novel pleiotropic loci underlying WHR and GSD with biological mechanisms outside of BMI. Mendelian randomization confirmed a robust WHR-GSD causal relationship (OR=1.50, 95%CI=1.35-1.65) which attenuated yet remained significant after adjusting for BMI (OR=1.17, 95%CI=1.09-1.26). Furthermore, observational analysis confirmed a positive association between general obesity and GSD, corroborated by a shared genetic basis (rg =0.40, P=2.16×10-43), multiple novel pleiotropic loci (N=11) and a causal relationship (OR=1.67, 95%CI=1.56-1.78). Conclusion: Both observational and genetic analyses consistently provide evidence on an association of central obesity with an increased risk of GSD, independent of general obesity. Our work highlights the need of considering both general and central obesity in the clinical management of GSD.

A high-sensitivity SnSe/Si heterojunction position-sensitive detector for ultra-low power detection.

Position-sensitive detectors (PSDs) based on the lateral photovoltaic effect are crucial components in non-contact distance measurement, process control, guidance systems, and other related applications. However, PSDs are challenging due to the narrow spectral range and low sensitivity, limiting further practical application. Here, we present an ultra-sensitive SnSe/Si PSD device. A large-area uniform SnSe nanorod (NR) array film was grown on Si using a glancing-angle magnetron sputtering deposition technique and a SnSe/Si heterojunction PSD device was fabricated. PSDs exhibit an excellent photoresponse in a wide spectral range of 405-980 nm, showing an ultrahigh position sensitivity of 1517.4 mV mm-1 and an excellent spectral sensitivity of 4 × 104 V W-1. More importantly, the detection limit power of the device is as low as 10 nW, indicating the outstanding potential for weak light detection. Based on the unique structural features and interface effect, the mechanisms for the remarkable performance of the fabricated SnSe/Si PSD device are clarified. This work indicates the large potential of SnSe/Si heterojunctions as a promising material for ultrasensitive optical position-sensitive devices.

Effect of no eyeglasses sales on the quality of eye care: an experimental evidence from China.

BACKGROUND: Eye examinations and eyeglasses acquisition are typically integrated into a cohesive procedure in China. We conducted a randomized controlled trial using incognito standardized patient (SP) approach to evaluate the impact of separating eyeglasses sales on the accuracy of final prescription. METHODS: 52 SPs were trained to provide standardized responses during eye examinations, and undergoing refraction by a senior ophthalmologist at a national-level clinical center. SPs subsequently received eye examinations at 226 private optical shops and public hospitals in Shaanxi, northwestern China. The visits were randomly assigned to either control group, where SPs would typically purchase eyeglasses after refraction, or treatment group, where SPs made an advance declaration not to purchase eyeglasses prior to refraction. The dioptric difference between the final prescriptions provided by local refractionists and expert in the better-seeing eye was determined using the Vector Diopteric Distance method, and the completeness of exams was assessed against national standards. Multiple regressions were conducted to estimate the impact of no eyeglasses sales on the accuracy of the final prescription of local refractionists, as well as the completeness of examinations. RESULTS: Among 226 eye exams (73 in public hospitals, 153 in private optical shops), 133 (58.8%) were randomized to control group and 93 (41.2%) to no eyeglasses sales group. The inaccuracy rate of final prescriptions provided by local refractionists (≥ 1.0 D, experts' final prescription as the reference) was 25.6% in control group, while 36.6% in no-sale group (P = 0.077). The likelihood of providing inaccurate final prescriptions was significantly higher in no-sale group compared to control group (OR = 1.607; 95% CI: 1.030 to 2.508; P = 0.037). This was particularly evident in private optical shops (OR = 2.433; 95% CI: 1.386 to 4.309; P = 0.002). In terms of process quality, the no-sale group performed significantly less subjective refraction (OR = 0.488; 95% CI: 0.253 to 0.940; P = 0.032) and less testing SP's own eyeglasses (OR = 0.424; 95% CI: 0.201 to 0.897; P = 0.025). The duration of eye exams was 3.917 min shorter (95% CI: -6.798 to -1.036; P = 0.008) in no-sale group. CONCLUSIONS: Separating eyeglasses sales from optical care could lead to worse quality of eye care. Policy makers should carefully consider the role of economic incentives in healthcare reform.

Dual roles of CCDC102A in governing centrosome duplication and cohesion.

In animal cells, the dysregulation of centrosome duplication and cohesion maintenance leads to abnormal spindle assembly and chromosomal instability, contributing to developmental disorders and tumorigenesis. However, the molecular mechanisms involved in maintaining accurate centrosome number control and tethering are not fully understood. Here, we identified coiled-coil domain-containing 102A (CCDC102A) as a centrosomal protein exhibiting a barrel-like structure in the proximal regions of parent centrioles, where it prevents centrosome overduplication by restricting interactions between Cep192 and Cep152 on centrosomes, thereby ensuring bipolar spindle formation. Additionally, CCDC102A regulates the centrosome linker by recruiting and binding C-Nap1; it is removed from the centrosome after Nek2A-mediated phosphorylation at the onset of mitosis. Overall, our results indicate that CCDC102A participates in controlling centrosome number and maintaining centrosome cohesion, suggesting that a well-tuned system regulates centrosome structure and function throughout the cell cycle.

High-Performance Flexible Broadband Photothermoelectric Photodetectors Based on Tellurium Films.

Mid- and far-infrared photodetectors that can operate at room temperature are essential for both civil and military applications. However, the widespread use of mid-to-far-infrared photonic technology faces challenges due to the need for low-temperature cooling of existing commercial semiconductors and the limited optical absorption efficiency of two-dimensional materials. We have utilized the photothermoelectric effect to fabricate a self-powered, broadband, and high-performance photodetector based on a one-dimensional tellurium nanorod array film. The device surpasses energy band gap limitations, functioning even at wavelengths up to approximately 10,600 nm. In particular, the detectivity of the device can reach 4.8 × 109 Jones at 4060 nm under room-temperature conditions, which is an order of magnitude higher than that of commercially available photodetectors. It demonstrates fast response and recovery times of 8.3 and 8.8 ms. Furthermore, the device demonstrates outstanding flexibility withstanding over 300 bending cycles and environmental stability. These results suggest a viable approach for designing and developing high-performance, room-temperature, wearable optoelectronic devices.

Epidemiological and Genetic Analyses of Schizophrenia and Breast Cancer.

BACKGROUND AND HYPOTHESIS: While the phenotypic association between schizophrenia and breast cancer has been observed, the underlying intrinsic link is not adequately understood. We aim to conduct a comprehensive interrogation on both phenotypic and genetic relationships between schizophrenia and breast cancer. STUDY DESIGN: We first used data from UK Biobank to evaluate a phenotypic association and performed an updated meta-analysis incorporating existing cohort studies. We then leveraged genomic data to explore the shared genetic architecture through a genome-wide cross-trait design. STUDY RESULTS: Incorporating results of our observational analysis, meta-analysis of cohort studies suggested a significantly increased incidence of breast cancer among women with schizophrenia (RR = 1.30, 95% CIs = 1.14-1.48). A positive genomic correlation between schizophrenia and overall breast cancer was observed (rg = 0.12, P = 1.80 × 10-10), consistent across ER+ (rg  = 0.10, P = 5.74 × 10-7) and ER- subtypes (rg = 0.09, P = .003). This was further corroborated by four local signals. Cross-trait meta-analysis identified 23 pleiotropic loci between schizophrenia and breast cancer, including five novel loci. Gene-based analysis revealed 27 shared genes. Mendelian randomization demonstrated a significantly increased risk of overall breast cancer (OR = 1.07, P = 4.81 × 10-10) for genetically predisposed schizophrenia, which remained robust in subgroup analysis (ER+: OR = 1.10, P = 7.26 × 10-12; ER-: OR = 1.08, P = 3.50 × 10-6). No mediation effect and reverse causality was found. CONCLUSIONS: Our study demonstrates an intrinsic link underlying schizophrenia and breast cancer, which may inform tailored screening and management of breast cancer in schizophrenia.

Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease: Prospective cohort study and genetic analyses.

BACKGROUND: While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD. METHODS: We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase / Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adj BMI]: Ncase / Ncontrol = 50,409/523,897) and for CAD ( Ncase / Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase / Ncontrol = 180,834/1,159,055). RESULTS: Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01-2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63-1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75 ), which was largely independent of BMI (T2DM adj BMI-CAD: rg = 0.31, P = 1.20 × 10 -36 ). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. CONCLUSION: Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Effect of melatonin on cryopreservation of Beijing you chicken (gallus gallus) spermatozoa.

Beijing You Chicken, a valuable local chicken breed from Beijing, China, was once listed as an endangered breed. From the point of view of conservation, the preservation of this breed is an important task for the local researchers. Semen cryopreservation is a popular method to maintain valuable species. However, during cryopreservation, semen is susceptible to oxidative damage. Melatonin is a potent antioxidant and free radical scavenger, so it has been selected to improve the efficiency of sperm cryopreservation. In this study, the chicken semen was treated with different concentrations of melatonin in the cryopreservation solution. The results showed that melatonin at concentrations of 10-3 M and 10-5 M significantly improved sperm progressive motility and total motility, respectively, compared to the control (P < 0.05). Melatonin at 10-3 M also significantly improved the plasma membrane and acrosome integrity of spermatozoa compared to the control. The mechanisms are that melatonin significantly reduces the level of ROS and preserves sperm mitochondrial membrane potential. Most importantly, the melatonin-treated cryopreserved chicken sperm after artificial insemination significantly increased the hatching rate of chicks compared to the control (p < 0.05). The results show that melatonin has a positive effect on the quality of the cryopreserved spermatozoa. These results provide the theoretical and practical basis for using melatonin to improve Beijing You Chicken conservation, and they may also be applicable to poultry as a whole.

Observational and genetic analyses of the bidirectional relationship between depression and hypertension.

BACKGROUND: While the association between depression and hypertension has been extensively investigated, the pattern and nature of such association remain inconclusive. We sought to investigate the bidirectional relationship between depression and hypertension and its causal. METHODS: We first performed observational analyses using longitudinal data from the UK Biobank. We then performed genetic analyses leveraging summary statistics from large-scale genome-wide association studies (GWASs) conducted in European ancestry for depression and hypertension. RESULTS: Observational analysis suggested a significant bidirectional phenotypic association between depression and hypertension (Depression â†’ Hypertension: HR = 1.27, 95 % CI: 1.19, 1.36; Hypertension â†’ Depression: HR = 1.65, 95 % CI: 1.58, 1.72). Linkage disequilibrium score regression demonstrated a positive genetic correlation between the two conditions (rg=0.15, P = 5.75 × 10-10). Bidirectional two-sample Mendelian randomization (MR) suggested that genetic liability to depression was significantly associated with an increased risk of hypertension (OR = 1.27, 95 % CI: 1.12, 1.43), while the genetic liability to hypertension was not associated with the risk of depression (OR = 1.01, 95 % CI: 0.99, 1.03). Multivariate MR, after adjusting for smoking, drinking, and body mass index, further supported an independent causal effect of genetic liability to depression on hypertension risk (OR = 1.10, 95 % CI: 1.02, 1.18). LIMITATIONS: (1) interference of confounders, (2) absence of adequate statistical power, and (3) limitation to European populations. CONCLUSION: Our study indicates depression is a causal risk factor for hypertension, whereas the reverse maybe not. Findings support that prevention of depression might help in decreasing hypertension incidence.