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Local genetic correlation evaluates the correlation of additive genetic effects between different traits across the same genetic variants at a genomic locus. It has been proven informative for understanding the genetic similarities of complex traits beyond that captured by global genetic correlation calculated across the whole genome. Several summary-statistics-based approaches have been developed for estimating local genetic correlation, including |$\rho$| -hess, SUPERGNOVA and LAVA. However, there has not been a comprehensive evaluation of these methods to offer practical guidelines on the choices of these methods. In this study, we conduct benchmark comparisons of the performance of these three methods through extensive simulation and real data analyses. We focus on two technical difficulties in estimating local genetic correlation: sample overlaps across traits and local linkage disequilibrium (LD) estimates when only the external reference panels are available. Our simulations suggest the likelihood of incorrectly identifying correlated regions and local correlation estimation accuracy are highly dependent on the estimation of the local LD matrix. These observations are corroborated by real data analyses of 31 complex traits. Overall, our findings illuminate the distinct results yielded by different methods applied in post-genome-wide association studies (post-GWAS) local correlation studies. We underscore the sensitivity of local genetic correlation estimates and inferences to the precision of local LD estimation. These observations accentuate the vital need for ongoing refinement in methodologies. [ABSTRACT FROM AUTHOR]

Purpose: Esophageal squamous cell carcinoma (ESCC) metastasizes in an unpredictable fashion to adjacent lymph nodes, including those along the recurrent laryngeal nerves (RLNs). This study is to apply machine learning (ML) for prediction of RLN node metastasis in ESCC. Methods: The dataset contained 3352 surgically treated ESCC patients whose RLN lymph nodes were removed and pathologically evaluated. Using their baseline and pathological features, ML models were established to predict RLN node metastasis on each side with or without the node status of the contralateral side. Models were trained to achieve at least 90% negative predictive value (NPV) in fivefold cross-validation. The importance of each feature was measured by the permutation score. Results: Tumor metastases were found in 17.0% RLN lymph nodes on the right and 10.8% on the left. In both tasks, the performance of each model was comparable, with a mean area under the curve ranging from 0.731 to 0.739 (without contralateral RLN node status) and from 0.744 to 0.748 (with contralateral status). All models showed approximately 90% NPV scores, suggesting proper generalizability. The pathology status of chest paraesophgeal nodes and tumor depth had the highest impacts on the risk of RLN node metastasis in both models. Conclusion: This study demonstrated the feasibility of ML in predicting RLN node metastasis in ESCC. These models may potentially be used intraoperatively to spare RLN node dissection in low-risk patients, thereby minimizing adverse events associated with RLN injuries. [ABSTRACT FROM AUTHOR]

• For the first time, LPCAT1 from the Large Yellow Croaker has been cloned, and its differential tissue expression has been explored. • This study is the first to investigate the affinity of LPCAT1 for different fatty acids in aquatic animals. • Knocking down LPCAT1 in the liver cells of the Large Yellow Croaker significantly alleviates inflammation. • Adding lysophosphatidylcholine to plant oil-based feed alleviates inflammation in the liver cells of the Large Yellow Croaker. In farmed fish, diets rich in palm oil have been observed to promote abnormal lipid build-up in the liver, subsequently leading to physiological harm and disease onset. Emerging research suggests that integrating phospholipids into the feed could serve as a potent countermeasure against hepatic impairments induced by vegetable oil consumption. Phosphatidylcholine is the most abundant type among phospholipids. In the metabolic processes of mammal, lysophosphatidylcholine acyltransferase 1 (LPCAT1), crucial for phosphatidylcholine remodeling, demonstrates a marked affinity towards palmitic acid (PA). Nonetheless, aspects concerning the cloning, tissue-specific distribution, and affinity of the LPCAT1 gene to diverse oil sources have yet to be elucidated in the large yellow croaker (Larimichthys crocea). Within the scope of this study, we successfully isolated and cloned the cDNA of the LPCAT1 gene from the large yellow croaker. Subsequent analysis revealed distinct gene expression patterns of LPCAT1 across ten different tissues of the species. The fully sequenced coding DNA sequence (CDS) of LPCAT1 spans 1503 bp and encodes a sequence of 500 amino acids. Comparative sequence alignment indicates that LPCAT1 shares a 69.75 % amino acid similarity with its counterparts in other species. Although LPCAT1 manifests across various tissues of the large yellow croaker, its predominance is markedly evident in the liver and gills. Furthermore, post exposure of the large yellow croaker's hepatocytes to varied fatty acids, PA has a strong response to LPCAT1. Upon the addition of appropriate lysolecithin to palm oil feed, the mRNA expression of LPCAT1 in the liver cells of the large yellow croaker showed significant variations compared to other subtypes. Concurrently, the mRNA expression of pro-inflammatory genes il-1β , il-6 , il-8 , tnf-α and ifn-γ in the liver tissue of the large yellow croaker decreased. Interestingly, they exhibit the same trend of change. In conclusion, we have cloned the LPCAT1 gene on fish successfully and find the augmented gene response of LPCAT1 in hepatocytes under PA treatment first. The results of this study suggest that LPCAT1 may be associated with liver inflammation in fish and offer new insights into mitigating liver diseases in fish caused by palm oil feed. [ABSTRACT FROM AUTHOR]

Genetic correlation is the correlation of phenotypic effects by genetic variants across the genome on two phenotypes. It is an informative metric to quantify the overall genetic similarity between complex traits, which provides insights into their polygenic genetic architecture. Several methods have been proposed to estimate genetic correlation based on data collected from genome-wide association studies (GWAS). Due to the easy access of GWAS summary statistics and computational efficiency, methods only requiring GWAS summary statistics as input have become more popular than methods utilizing individual-level genotype data. Here, we present a benchmark study for different summary-statistics-based genetic correlation estimation methods through simulation and real data applications. We focus on two major technical challenges in estimating genetic correlation: marker dependency caused by linkage disequilibrium (LD) and sample overlap between different studies. To assess the performance of different methods in the presence of these two challenges, we first conducted comprehensive simulations with diverse LD patterns and sample overlaps. Then we applied these methods to real GWAS summary statistics for a wide spectrum of complex traits. Based on these experiments, we conclude that methods relying on accurate LD estimation are less robust in real data applications due to the imprecision of LD obtained from reference panels. Our findings offer guidance on how to choose appropriate methods for genetic correlation estimation in post-GWAS analysis. [ABSTRACT FROM AUTHOR]

Laser shock hole-clinching is a novel mechanical joining process in which the shock wave pressure induced by a high-energy pulsed laser is employed as a punch. This process is quite suitable for the joining of two dissimilar materials with significant differences in plasticity and strength. However, the effect of key process parameters on the forming quality of joints by laser shock hole-clinching is less concerned. In this study, the influence of laser power density, spacer height, number of laser pulse, and initial grain size of metal foils on the forming quality of Cu-Fe joints was experimentally investigated. The characteristics of interlock value and thinning rate distribution under various process parameters were systematically examined. It is revealed that laser shock hole-clinching process can be divided into the confined bulging and interlock formation stages. Based upon the examination of substandard joints, the defects in laser shock hole-clinching process are classified which contains no interlock, nonuniform interlock, bottom and neck fracture. It is found that the thinnest position of joints locates at the region in contact with the upper corner of the joining partner II in which extensive plastic deformation occurs related to the force acting during clinching process. The interlock value increases significantly as the enlargement of initial grain size, whereas the deviation also becomes larger due to the inhomogeneous plastic deformation for the metal foil with coarse grains. Moreover, the ratio of spacer height to the thickness of the joining partner II affects the thinning rate distribution and interlock value of joints. The spacer height equaling to the thickness of the joining partner II is recommended within the given parameters. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents failure analysis on cracking of packing plate in a super high-pressure compressor. Analytical stresses resulted from shrink-fit assembly are introduced and related with the diametric interference to quantitatively study the influence of diametric interference on local stresses in the packing plate. Residue stresses in the region of interest are measured by X-ray diffraction method under the assembly and disassembly states of the packing plate respectively. In addition, fractographic and metallurgical examinations are carried out to check characteristics of the crack and possible material defects. Our failure analysis indicated that the main reason for the cracking of packing plate is the synergistic effect of the inclusions in the material and the high tensile stresses due to less diametric interference and stress concentration at the crack initiation site. [Copyright &y& Elsevier]

Abstract: The hydroxyalkylation reactions of aceanthrenequinone (6) and acenapthenequinone (7) with a series of arenes have been studied. In reactions with the Brønsted superacid CF3SO3H (triflic acid), the condensation products are formed in good yields (58–99%, 10 examples) with high regioselectivity. Computational studies were also done to examine the structures and energies of mono- and diprotonated species from 6 and 7. The results from the condensation reactions are consistent with the formation of superelectrophilic species involving protosolvation of carboxonium ion intermediates. [Copyright &y& Elsevier]

Background: Recent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific effect on cognitive impairment in BD subtype II (BD-II) remains obscure. The aim of the current study was to examine whether cognitive deficits differ by gender in youth with BD-II depression. Method: This cross-sectional study recruited 125 unmedicated youths with BD-II depression and 140 age-, sex-, and education-matched healthy controls (HCs). The Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess cognitive functions. Mood state was assessed using the 24-item Hamilton Depression Rating Scale (24-HDRS) and the Young Mania Rating Scale (YMRS). Multivariate analysis of covariance (MANCOVA) was conducted. Result: ​Compared with HCs, patients with BD-II depression had lower scores on MCCB composite and its seven cognitive domains (all p < 0.001). After controlling for age and education, MANCOVA revealed significant gender-by-group interaction on attention/vigilance (F = 6.224, df = 1, p = 0.013), verbal learning (F = 9.847, df = 1, p = 0.002), visual learning (F = 4.242, df = 1, p = 0.040), and composite (F = 8.819, df = 1, p = 0.003). Post hoc analyses suggested that males performed worse in the above-mentioned MCCB tests than females in BD-II depression. Conclusion: Our study demonstrated generalized cognitive deficits in unmedicated youths with BD-II depression. Male patients performed more serious cognitive impairment on attention/vigilance, verbal learning, and visual learning compared to female patients. [ABSTRACT FROM AUTHOR]

Heritability is a fundamental concept in genetic studies, measuring the genetic contribution to complex traits and bringing insights about disease mechanisms. The advance of high-throughput technologies has provided many resources for heritability estimation. Linkage disequilibrium (LD) score regression (LDSC) estimates both heritability and confounding biases, such as cryptic relatedness and population stratification, among single-nucleotide polymorphisms (SNPs) by using only summary statistics released from genome-wide association studies. However, only partial information in the LD matrix is utilized in LDSC, leading to loss in precision. In this study, we propose LD eigenvalue regression (LDER), an extension of LDSC, by making full use of the LD information. Compared to state-of-the-art heritability estimating methods, LDER provides more accurate estimates of SNP heritability and better distinguishes the inflation caused by polygenicity and confounding effects. We demonstrate the advantages of LDER both theoretically and with extensive simulations. We applied LDER to 814 complex traits from UK Biobank, and LDER identified 363 significantly heritable phenotypes, among which 97 were not identified by LDSC. [ABSTRACT FROM AUTHOR]

Background. Middle-aged (45-59 years old) patients with major depressive disorder (MDD) have a predilection for dementia and cognitive disorders (CDs); however, the characteristics and mechanisms of CDs in these patients remain unclear. There are also known connections between thyroid-stimulating hormone (TSH), brain biochemical metabolism, and cognitive function (CF); however, there is scanty of information about these connections in middle-aged MDD patients. Methods. Cognitive assessment was performed on 30 first-episode, untreated middle-aged patients with MDD and 30 well-matched healthy controls (HCs) using the MATRICS Consensus Cognitive Battery (MCCB). N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in the prefrontal cortex (PFC) and cerebellum were also obtained via proton magnetic resonance spectroscopy (1H-MRS), and the TSH level was measured by chemiluminescence analysis. Results. MDD patients presented significantly lower processing speed, working memory, verbal learning, reasoning problem-solving, visual learning, and composite cognition scores than controls, with a statistically lower NAA/Cr ratio in the right cerebellum. Age was positively related to reasoning problem-solving in the MDD group (r = 0.6249 , p = 0.0220). Education also showed a positive association with visual learning, social cognition, and composite cognition. The 24-item Hamilton Depression Rating Scale (HDRS-24) score was negatively related to all domains of CF. TSH levels were markedly decreased in the MDD group, and a positive connection was determined between the NAA/Cr ratio in the right PFC and the TSH level. Conclusions. Middle-aged MDD patients have multidimensional CDs. There are changes in PFC and cerebellar biochemical metabolism in middle-aged patients with MDD, which may be related to CDs or altered TSH levels. [ABSTRACT FROM AUTHOR]

Aimin Luo,3 Shunkai Lai,1 Tingting He,4 Yuchong Luo,2 Ying Wang,5 Yiliang Zhang,1 Shiyi Shen,4 Hui Huang,4 Shenglin Wen,2 Yanbin Jia11Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, People's Republic of China; 2Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, People's Republic of China; 3Department of Psychology, Guangdong Sanjiu Brain Hospital, Guangzhou, Guangdong Province, People's Republic of China; 4School of Management, Jinan University, Guangzhou, Guangdong Province, People's Republic of China; 5Medical Imaging Center, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, People's Republic of China*These authors contributed equally to this workCorrespondence: Yanbin JiaDepartment of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, People's Republic of ChinaTel +86 13392489168Fax +86 020-38688888Email [email protected] Purpose: This study aimed to investigate the mechanism of working memory (WM) impairment in drug-naive obsessive-compulsive disorder (OCD) by using neuropsychological tests and proton magnetic resonance spectroscopy (1H-MRS). Patients and Methods: A total of 55 patients with drug-naive OCD and 55 healthy controls (HCs) were recruited for this study. The working memory (WM) was evaluated using the digit span test (DST), visual space memory test (VSMT), and the 2-back task and stroop color word test (SCWT). The bilateral metabolite levels of the prefrontal cortex (PFC) were evaluated by 1H-MRS, then determined the ratios of N-acetyl aspartate (NAA), choline-containing compounds (Cho), and myo-inositol (MI) to creatine (Cr). The independent sample t-test was used to analyse the differences in WM performance and neurometabolite ratios. Multivariate linear regression analysis was performed to screen the influential factors of WM, with an introduction level of 0.05 and a rejection level of 0.10. Results: 1) Patients with OCD performed significantly worse on DST (score), VSMT (score), 2-back task (accuracy rate), SCWT (execution time) when compared with HCs. 2) NAA/Cr and Cho/Cr in the left PFC (lPFC) and MI/Cr ratios in the bilateral PFC of OCD patients were significantly lower when compared to HCs. 3) For OCD patients, the NAA/Cr ratio in the lPFC was negatively correlated with the score of DST (forwards), the Cho/Cr ratio in the lPFC was positively correlated with the accuracy rate of 2-back task, and the MI/Cr ratio in the right PFC (rPFC) was positively correlated with the score of DST (forwards) and the accuracy rate of VSMT. We also found that the compulsive symptoms showed a positive correlation with MI/Cr ratio of the rPFC. Conclusion: Drug-naive OCD patients have demonstrated WM impairments, including phonological loop, visual-spatial sketchpad and central executive system, and the WM impairments might be associated with hypometabolism in the PFC, especially the lPFC. [ABSTRACT FROM AUTHOR]

Laser shock hole-clinching is a high–strain rate mechanical joining process in which the metal foils are joined together based on plastic deformation generated by a laser-induced shock wave. In the process, fracture is a typical defect and seriously influences the clinching quality and production efficiency of joints. However, the classification and variation of fracture modes in laser shock hole-clinching are of less concern. In this study, the fracture mode of Cu-Fe joints in laser shock hole-clinching was experimentally investigated. Both optical microscopy and scanning electron microscopy were adopted to analyze the fracture surface morphology of clinched joints. The influence of laser power density, laser spot diameter, the initial grain size and thickness of metal foil, and spacer height on the fracture mode of joints was evaluated. It is revealed that the temperature increase caused by high–strain rate plastic deformation has no impact on the fracture behavior of the joining partners. Fracture always occurs on joining partner I, and it can be divided into four modes, including bottom surface fracture, bottom corner fracture, neck fracture, and mixed fracture. It is found that fracture on the bottom surface is seldom seen but mixed fracture accounts for most of the cracked specimens. Neck tensile fracture rarely appears alone, and it usually exists accompanied by fracture on the bottom corner. The fracture mode varies from a tensile fracture mode on the bottom corner to a mixed fracture mode and then to a shear fracture mode on the neck with the enhancement of laser power density. In addition, the initial grain size of joining partner I has a significant impact on the fracture mode of clinched joints. The fracture mode varies from bottom corner fracture to mixed fracture in relation to the change of mechanical properties of metal foil with an enlarged grain size. However, the mixed fracture mode always appears with the enlargement of both laser spot diameter and spacer height. [ABSTRACT FROM AUTHOR]

Some heterogeneous catalysts, cupric oxide supported on different supports, were prepared and employed to catalyze the cyclopropanation of styrene and 2,5-dimethyl-2,4-hexadiene with ethyl diazoacetate (EDA). The catalytic performance for cyclopropanation strongly depends on the nature of the support. A novel catalyst, CuO/TiO2-Al2O3, in which Al2O3 is modified with a monolayer TiO2, is found to be most active and selective for the cyclopropanation reaction. The yields of 93 and 94% cyclopropanes are obtained for styrene and 2,5-dimethyl-2,4-hexadiene at 40 °C as the substrates, respectively. The activity and selectivity in cyclopropanes are optimized with a monolayer dispersion of cupric oxide on the corresponding supports. [Copyright &y& Elsevier]