Search

Human genetic studies of common variants have provided substantial insight into the biological mechanisms that govern ovarian ageing1. Here we report analyses of rare protein-coding variants in 106,973 women from the UK Biobank study, implicating genes with effects around five times larger than previously found for common variants (ETAA1, ZNF518A, PNPLA8, PALB2and SAMHD1). The SAMHD1association reinforces the link between ovarian ageing and cancer susceptibility1, with damaging germline variants being associated with extended reproductive lifespan and increased all-cause cancer risk in both men and women. Protein-truncating variants in ZNF518Aare associated with shorter reproductive lifespan—that is, earlier age at menopause (by 5.61 years) and later age at menarche (by 0.56 years). Finally, using 8,089 sequenced trios from the 100,000 Genomes Project (100kGP), we observe that common genetic variants associated with earlier ovarian ageing associate with an increased rate of maternally derived de novo mutations. Although we were unable to replicate the finding in independent samples from the deCODE study, it is consistent with the expected role of DNA damage response genes in maintaining the genetic integrity of germ cells. This study provides evidence of genetic links between age of menopause and cancer risk.

The goal of the present study was to establish a rapid, simple method for simultaneous allergy testing of sera from multiple fish-allergic patients. Sera from fish-allergic patients were pooled and used for capturing allergens in fish muscle of crucian carp (Carassius auratus), which was studied as a fish model. Sarcoplasmic proteins of crucian carp (Carassius auratus) were extracted for the analysis of allergens. Anti-human IgE antibody–functionalized magnetic beads were utilized to collect IgE antibodies from human pooled sera. The isolation of allergenic proteins was immunomagnetically performed in microfluidic channels, and the elution of the captured allergenic proteins was done with 5% (v/v) acetic acid aqueous solution. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and peptide mass fingerprinting were used for the analysis of tryptic digests of eluted proteins. Ten potential allergenic proteins were identified from crucian carp (Carassius auratus). The present protocol provides a rapid, efficient, and simple method for simultaneous detection of multiple allergens, based on multitargeted antibodies from pooled sera of allergic patients. The constructed multiple antibody-modified MBs can be applied for the deallergenicity of food matrices. The efficiency of allergen detection can be greatly improved, with promising application in allergen discovery and filtration for other muscle-based foods.

A regiodivergent allylation of 1H-indoles highly selectively at the C3 and N1 positions with β-acyl allylic sulfides through desulfurative C–C/C–N bond-forming reactions has been developed under mild conditions. Notably, the remarkable site-selective switch can be achieved by a delicate choice of solvents and bases. This cost-efficient method displays a broad substrate scope, good functional compatibility, and excellent site-selectivity, thus offering a divergent synthesis of indole substituted α-branched enones, which possess diverse potential opportunities for further applications and derivatization.

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.

Single-image super-resolution (SISR) typically focuses on restoring various degraded low-resolution (LR) images to a single high-resolution (HR) image. However, during SISR tasks, it is often challenging for models to simultaneously maintain high quality and rapid sampling while preserving diversity in details and texture features. This challenge can lead to issues such as model collapse, lack of rich details and texture features in the reconstructed HR images, and excessive time consumption for model sampling. To address these problems, this paper proposes a Latent Feature-oriented Diffusion Probability Model (LDDPM). First, we designed a conditional encoder capable of effectively encoding LR images, reducing the solution space for model image reconstruction and thereby improving the quality of the reconstructed images. We then employed a normalized flow and multimodal adversarial training, learning from complex multimodal distributions, to model the denoising distribution. Doing so boosts the generative modeling capabilities within a minimal number of sampling steps. Experimental comparisons of our proposed model with existing SISR methods on mainstream datasets demonstrate that our model reconstructs more realistic HR images and achieves better performance on multiple evaluation metrics, providing a fresh perspective for tackling SISR tasks.

NiCoFe alloy, a medium-entropy alloy, shows potential for applications in extreme environments. However, there is a theoretical barrier concerning the unclear understanding of its high-temperature dislocation motion mechanism. The load response exhibits distinct signatures relevant to thermal activation, most notably a decrease in critical force (i.e., softening) from cryogenic to elevated temperatures, e.g., from 200 to 1000 K. The onset of plasticity is characterized by the nucleation of stacking faults and prismatic loops at low temperatures, whereas the surface nucleation of Shockley partial dislocations dominates plasticity at elevated temperatures. We show that thermal effects lead to non-uniform atom pile-ups and control the rate of phase transformation with increasing indentation depth. The findings in this work extend the understanding of the mechanical response of NiCoFe alloys under indentation at different temperatures, shedding light on the underlying dislocation motion mechanisms and surface deformation characteristics. The observed transformation-induced plasticity mechanism has implications for the properties of medium-entropy alloys and their potential applications in extreme environments.

Recently, the projected Jacobi (PJ) and projected Gauss-Seidel (PGS) iteration methods have been studied for solving the horizontal linear complementarity problems (HLCPs). To further improve the convergence rates of the PJ and PGS iteration methods, by using the successive overrelaxation (SOR) matrix splitting technique, a projected SOR iteration method is introduced in this paper to solve the HLCP. Convergence analyses are carefully studied when the system matrices are strictly diagonally dominant and irreducibly diagonally dominant. The newly obtained convergence results greatly extend the current convergence theory. Finally, two numerical examples are given to show the effectiveness of the proposed PSOR iteration method and its advantages over the recently proposed PJ and PGS iteration methods.

In this paper, the modulus-based matrix splitting (MMS) iteration method is extended to solve the horizontal quasi-complementarity problem (HQCP), which is characterized by the presence of two system matrices and two nonlinear functions. Based on the specific matrix splitting of the system matrices, a series of MMS relaxation iteration methods are presented. Convergence analyses of the MMS iteration method are carefully studied when the system matrices are positive definite matrices and H+-matrices, respectively. Finally, two numerical examples are given to illustrate the efficiency of the proposed MMS iteration methods.

The mathematical formulation of the mixed-cell-height circuit legalization (MCHCL) problem can be expressed by a linear complementarity problem (LCP) with the system matrix being a block two-by-two saddle point matrix. Based on the robust modulus-based matrix splitting (RMMS) iteration method and its two-step improvement (RTMMS) studied recently, the well-known Hermitian and skew-Hermitian splitting iteration method and the generalized successive overrelaxation iteration method for solving saddle point linear systems, two variants of robust two-step modulus-based matrix splitting (VRTMMS) iteration methods are proposed for solving the MCHCL problem. Convergence analyses of the proposed two iteration methods are studied in detail. Finally, five test problems are presented. Numerical results show that the proposed two VRTMMS iteration methods not only take full use of the sparse property of the circuit system but also speed up the computational efficiency of the existing RMMS and RTMMS iteration methods for solving the MCHCL problem.

Zoonoses account for the majority of emerging infectious diseases and pose a serious threat to human and animal health. Under global warming and climate change, zoonoses are significantly affected by influencing hosts, vectors, and pathogen dynamics as well as their interactions. Traditional zoonoses surveillance relies on molecular or serological diagnostic methods to monitor pathogens from animal or patient samples, which may miss the early warning signs of pathogens spillover from the environment. Nowadays, new technologies such as remote sensing, environment-based screening, multi-omics, and big data science facilitate comprehensive active surveillance, offering great potential for early warning and prediction. Despite the recent technological advances, there is few reviews that explores the integration of cutting-edge technologies aimed at constructing a robust early warning system. Therefore, we discussed the opportunities, barriers, and limitations of interdisciplinary emerging technologies for exploring early warning and surveillance of zoonoses. This systematic review summarized a practical framework for early surveillance integrated with a modified SEIR model for zoonoses in the context of climate change. It also outlined challenges and future prospects in terms of data sharing, early detection of unknown zoonoses and the move towards global surveillance.

Our understanding of the genetics of the human cerebral cortex is limited both in terms of the diversity and the anatomical granularity of brain structural phenotypes. Here we conducted a genome-wide association meta-analysis of 13 structural and diffusion magnetic resonance imaging-derived cortical phenotypes, measured globally and at 180 bilaterally averaged regions in 36,663 individuals and identified 4,349 experiment-wide significant loci. These phenotypes include cortical thickness, surface area, gray matter volume, measures of folding, neurite density and water diffusion. We identified four genetic latent structures and causal relationships between surface area and some measures of cortical folding. These latent structures partly relate to different underlying gene expression trajectories during development and are enriched for different cell types. We also identified differential enrichment for neurodevelopmental and constrained genes and demonstrate that common genetic variants associated with cortical expansion are associated with cephalic disorders. Finally, we identified complex interphenotype and inter-regional genetic relationships among the 13 phenotypes, reflecting the developmental differences among them. Together, these analyses identify distinct genetic organizational principles of the cortex and their correlates with neurodevelopment.

The emergence of Mo2C-based catalysts in recent years has been favored as promising contender within diverse class MXenes. In terms of rapid development in the photocatalytic application, these intriguing compounds exhibit excellent photocatalytic performance because of their superior optical properties and peculiar structure characteristics. Unfortunately, a systematic review of Mo2C-based catalysts is lacking. In this review, we abstract the implication of structure—property relationship of emerging Mo2C-based MXenes materials and their applications toward the photocatalytic hydrogen evolution reaction (HER). Furthermore, synthetic pathways to prepare high-quality, low cost Mo2C-based MXenes materials and their outcomes for high HER applications are systematically described. Finally, several insights are provided into the prospects and future challenges for the development of highly reactive Mo2C-based MXenes materials, which present large range opportunities in this promising 2D materials for green and clean energy in environmental fields. This review provides a comprehensive scientific guide to the preparation, modification, and photocatalytic HER of MXenes-based materials.

The carbon-containing molecule can be used as an NMR probe to explore the acidic and structural features of various catalytic materials. Thereinto, although mesityl oxide (MO) has been extensively employed to determine the acidity of solution and ionic liquid systems, could it be utilized to characterize the acidic properties of solid acid catalysts? In this work, on the basis of a series of isolated Brønsted and Lewis acid models with varied acid strengths, the adsorption configurations and corresponding 13C chemical shifts of adsorbed MO molecules have been comprehensively studied by means of a theoretical investigation approach. Among them, both the 13C chemical shift difference between β and α carbon atoms (Δδ), and the 13C chemical shift of β carbon atoms (δ13Cβ) in adsorbed MO molecules were explicitly demonstrated to be closely related to the intrinsic acid strength of Brønsted acid sites. These correlations could be utilized to quantitatively scale the Brønsted acid strength of solid acid catalysts. Besides, a moderate relationship was theoretically derived for the relevant 13C NMR parameters and intrinsic Lewis acid strength.

Raptor, a regulatory-associated protein of mTOR, has been genetically proved to be an important regulator in lipogenesis. However, its druggable potential is rarely investigated, largely due to the lack of an inhibitor. In this study, the antiadipogenic screening of a daphnane diterpenoid library followed by target fishing led to the identification of a Raptor inhibitor, 1c(5/7/6 carbon ring with orthoester and chlorine functionalities). Pharmacodynamic studies verified that 1cis a potent and tolerable antiadipogenic agent in vitro and in vivo. Mechanistic studies revealed that the targeting of Raptor by 1ccould block the formation of mTORC1 and then downregulate the downstream S6K1- and 4E-BP1-mediated C/EBPs/PPARγ signaling, eventually retarding adipocyte cell differentiation at the early stage. These findings suggest that Raptor can be explored as a novel therapeutic target for obesity and its related complications, and 1cas the first Raptor inhibitor may provide a new therapeutic option for these conditions.

In this study, a novel pressure-induced supercritical phase nucleation method is proposed to synthesize monolayer MoS2films, which is promoter free and can avoid contamination of films derived from these heterogeneous promoters in most of the existing techniques. The low-crystallinity and size-controlled MoO2(acac)2particles are recrystallized on the substrate via the pressure-sensitive solvent capacity of supercritical CO2and these particles are used as growth sites. The size of single-crystal MoS2on the substrate is found to be dependent on the wetting area of the pyrolyzed precursor droplets (MoO2) on the surface, and the formation of continuous films with high coverage is mainly controlled by the coalescence of MoO2droplets. It is enhanced by the increase of the nucleation site density, which can be adjusted by the supersaturation of the supercritical fluid solution. Our findings pave a new way for the controllable growth of MoS2and other two-dimensional materials and provide sufficient and valuable evidence for vapor–liquid–solid growth.

Objective: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder involving the orbital tissue. This study aimed to understand the role of regulatory T cells (Tregs) in TAO during 12-week systemic glucocorticoid (GC) treatment. Methods: Thirty-two moderate-severe TAO patients with a clinical activity score (CAS) ≥3/7 or with prolonged T2 relaxation time (T2RT) on at least one side of extraocular muscle (EOM) were enrolled. The percentage of the peripheral CD4+CD25(high)CD127(−/low) Tregs was analyzed using flow cytometry before and after the GC treatment. The activity and severity of TAO, T2RT, and the clinical outcomes after the GC treatment were assessed. Their correlation with the peripheral Tregs was investigated. Results: There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response. A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement. Conclusion: Treg reduction after systemic GC therapy is indicative of a poor therapeutic response. Accordingly, dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.

A field experiment was carried out to evaluate the effects of drip fertigation combined with plant hedgerows on nitrogen and phosphorus runoff losses in intensive pear orchards in the Tai Lake Basin. Nitrogen and phosphorus runoff over a whole year were measured by using successional runoff water collection devices. The four experimental treatments were conventional fertilization (CK), drip fertigation (DF), conventional fertilization combined with plant hedgerows (C+H), and drip fertigation combined with plant hedgerows (D+H). The results from one year of continuous monitoring showed a significant positive correlation between precipitation and surface runoff discharge. Surface runoff discharge under the treatments without plant hedgerows totaled 15.86% of precipitation, while surface runoff discharge under the treatments with plant hedgerows totaled 12.82% of precipitation. Plant hedgerows reduced the number of runoff events and the amount of surface runoff. Precipitation is the main driving force for the loss of nitrogen and phosphorus in surface runoff, and fertilization is an important factor affecting the losses of nitrogen and phosphorus. In CK, approximately 7.36% of nitrogen and 2.63% of phosphorus from fertilization entered the surface water through runoff. Drip fertigation reduced the accumulation of nitrogen and phosphorus in the surface soil and lowered the runoff loss concentrations of total nitrogen (TN) and total phosphorus (TP). Drip fertigation combined with plant hedgerows significantly reduced the overall TN and TP losses by 45.38 and 36.81%, respectively, in comparison to the CK totals. Drip fertigation increased the vertical migration depth of nitrogen and phosphorus nutrients and reduced the accumulation of nitrogen and phosphorus in the surface soil, which increased the pear yield. The promotion of drip fertigation combined with plant hedgerows will greatly reduce the losses of nitrogen and phosphorus to runoff and maintain the high fruit yields in the intensive orchards of the Tai Lake Basin.

(Sn1−xZnx)57(In0.78Bi0.22)43(x=0.10, 0.15, 0.20, at.%) quaternary alloys were designed and characterized based on the multi-principal-element mixing concept in order to develop a lead-free solder suitable for low temperature soldering in three-dimensional integrated circuit. The microstructure, thermal properties and wetting properties of the alloys were investigated using scanning electron microscope, X-ray diffractometer and differential scanning calorimeter. The results show that the alloys consist of intermetallic compounds (IMCs), BiIn2and In0.2Sn0.8, and Zn-rich solid solution. With the increase of Zn content, the volume fractions of the BiIn2and Zn-rich phases increase accordingly. The alloys exhibit low melting points of about 70 °C, due to the formation of the low-melting-point In0.2Sn0.8and BiIn2IMCs. The alloys show good wetting properties with wetting angle of about 40°. At the solder joints between the alloys and Cu layer, a thin and tough Cu5Zn8layer is formed, which is supposed to improve the joint reliability. It is demonstrated that the welding performance of solders can be effectively enhanced by designing solders through the multi-principal-element mixing concept.

The discharge of industrial oily wastewater and oil spill accidents has resulted in significant environmental pollution, creating an urgent need for the treatment of oily wastewater. Nanofiber membranes, known for their high stability, flux, and efficiency, are widely employed in oil–water separation. This study systematically compared the performance of polyacrylonitrile/graphene oxide (PAN/GO) composite nanofiber membranes prepared through immersion and electrospinning methods for oily wastewater treatment. Experimental findings demonstrated that immersion-prepared membranes achieved high flux (772.9 ± 2.9 L·m−2·h−1, n-hexane/water mixture) and efficiency (98.8%) at a GO concentration of 1.0 g/mL. On the other hand, electrospinning-prepared membranes exhibited superior flux (1500.3 ± 4.4 L·m−2·h−1, n-hexane/water mixture) and efficiency (99.6%) at a higher GO concentration (1.5 g/mL). This membrane displayed excellent stability, maintaining their exceptional performance even after ten cycles of separation. This study compared the advantages and disadvantages of the two methods for preparation of PAN/GO composite nanofiber membrane, offering valuable guidance for practical applications.

Chinese soft-shelled turtle (Pelodiscus sinensis) is an important aquaculture species in China. However, with the continuous development of P. sinensiscultures, problems related to germplasm degradation and population mixing have become increasingly prominent. This has seriously affected the protection and utilization of germplasm resources by P. sinensis. To broaden the understanding of the germplasm resources of P. sinensisand improve the efficiency of germplasm identification, Super-GBS sequencing technology was used to conduct population genetic analysis of P. sinensissamples from six different populations distributed in five provinces. As a result, 1464,488 SNPs were identified. Genetic structure analysis revealed that the six P. sinensispopulations could be divided into three sub-populations. The genetic differentiation coefficient of the DT and CY populations was very low (Fst=0.0088), indicating that differentiation had not yet occurred. Additionally, 15 KASP core markers for the identification of P. sinensispopulations were developed using KASP typing technique for the first time. Genetic information can lay a foundation for the protection and utilization of germplasm resources by P. sinensis, and the fingerprinting database developed in this study provides a practical tool for authenticating P. sinensis.

To further accelerate the convergence rate of the recent proposed modified modulus-based matrix splitting (MMMS) iteration method for solving the implicit complementarity problems, by using the two-step iteration methodology, a class of modified two-step modulus-based matrix splitting (MTMMS) iteration methods are studied in this paper. The convergence analyses of the MTMMS iteration method are carefully studied when the system matrix is a positive definite matrix or an H+-matrix. Finally, two numerical experiments are presented. Numerical results show that the proposed MTMMS iteration method performs much better than the existing MMMS iteration method.

Introduction:A strong association was previously established between body mass index (BMI) and female reproductive system tumors; however, the causal relationship is unclear. We conducted a Mendelian randomization (MR) study to further explore this association. Methods:Genetic information for BMI was retrieved from a published genome-wide association study involving 339,224 participants. Genetic associations with five common female reproductive system tumors were obtained from the FinnGen, UK Biobank studies, and other large consortia. Results:Genetic predisposition towards BMI exhibits a significant association with multiple tumors of the female reproductive system. Specifically, for every 1-unit increase in BMI log-transformed odds ratio (OR). The OR fluctuations overall for patients with breast cancer ranged from 0.661 to 0.996 (95% confidence interval [CI],0.544-1.000, P < 0.05). When stratified by estrogen receptor (ER) status, the OR for patients with ER (+) breast cancer ranged from 0.782 to 0.844 (95% CI, 0.616-0.994, P < 0.05) and that for those with ER (-) breast cancer ranged from 0.663 to 0.789 (95% CI, 0.498-0.991, P < 0.05). Additionally, ORs were as follows for cancer types: 1.577–1.908 (95% CI, 1.049-2.371, P < 0.05) for endometrial carcinoma; 1.216–1.303 (95% CI, 1.021-1.591, P < 0.05) for high-grade serous ovarian cancer; 1.217 (95% CI, 1.034-1.432, P < 0.05) for low-grade malignant serous ovarian cancer; and 1.502 (95% CI, 1.112-2.029, P < 0.05) for endometrioid ovarian carcinoma. Furthermore, our findings indicated that genetic predisposition towards BMI did not exhibit a causal association with uterine fibroids, cervical precancerous lesions, or cervical cancer itself. Conclusion:A genetic association was established between a high BMI and high risk of developing multiple tumors of the female reproductive system and their associated subtypes. This underscores the significance of taking measures to prevent reproductive system tumors in women who have a high BMI.

This paper puts forward an unprecedented avoidance-striking-arrival problem aiming to address the need for tank's uncertain mechanical systems on the intelligent battlefield. The associated system uncertainties (possibly rapid) are time-varying but bounded (possibly unknown). The goal is to design a controller that enables the tank to aim at and attack the enemy tank while keeping itself (out of the enemy fire zone). The tank maintains this condition until reaching the predefined region. In this paper, an approximate constraint following control method is adopted to solve this problem, and the original constraints are creatively divided into two categories: the avoidance - tracking constraint and the striking - arrival constraint. An adaptive robust control method is proposed and consequently verified through simulation experiments. It is proved that the system fully obeys the avoidance - tracking - constraint and strictly obeys the striking - arrival constraint under the control input τ. Besides, the control of the tank vehicle running system and tank gun bidirectional stabilization system are unified to deal with the control signal delay caused by complex uncertainties on the battlefield. Overall, this paper reduced the delay of signal transmission in the system while solved the avoidance - striking - arrival problem.