Forensic efficiency and population genetic construction of Guizhou Gelao minority from Southwest China revealed by a panel of 23 autosomal STR loci.

Short tandem repeats (STRs) are the most common genetic markers in forensic and human population genetics due to their high polymorphism, rapid detection, and reliable genotyping. To adapt the rapid growth of forensic DNA database and solve problems in disputed cases, a panel of 23 autosomal STR loci with high discriminating ability was constructed recently. The Tai-Kadai-speaking Gelao is the most ancient indigenous minority in Guizhou province, however, the forensic efficiency and population genetic structure remain poorly explored. Here, 490 Guizhou Gelao individuals from Southwest China were genotyped with the panel of 23 STRs using the Huaxia Platinum Kit. A total of 265 alleles were screened. The combined discrimination power and the combined probability of paternity were 0.9999 and 0.9999, respectively. This indicated the 23 loci had higher discrimination power in Guizhou Gelao and could be applied to forensic practice. Comprehensive population structures with reference populations from China and abroad using the neighbour-joining phylogenetic tree (N-J tree), multidimensional scaling, principal component analysis and heatmap demonstrated that Guizhou Gelao was genetically closer to Guizhou Han than other populations. Moreover, our results showed that a complex phylogenetic model was influenced by ethnic, geographic, and linguistic factors. Key points: The first batch of genetic data for 23 autosomal STRs in 490 Geolao individuals from Guizhou was provided.The 23 STR panel can afford high genetic polymorphisms and discrimination power and can be efficiently applied to forensic practice in Guizhou Gelao population.A complex phylogenetic model influenced by ethnic, geographic, and linguistic factors was uncovered.

Benefits of Chinese family caregivers of patients with urostomy: a qualitative study.

BACKGROUND: Family caregivers, also known as informal caregivers, are critical for the home care of patients with urostomy. The present study aimed to investigate the benefits of family caregivers in China while taking care of patients with urostomy from a positive perspective. METHODS: A qualitative research design was adopted, with a thematic analysis. The qualitative research software NVivo was used for data analysis. Twenty-two family caregivers of urostomy patients participated in an in-depth interview for 60-90 min. A qualitative analysis was performed using a thematic approach in accordance with the six-stage thematic analysis process reported by Braun and Clarke (2006). RESULTS: The following four benefits were identified: mastering knowledge and skills, promoting self-growth, establishing close family ties, and changing the way of life. Among these four themes, 11 sub-themes were constructed by coders. CONCLUSIONS: This study provides new insights into intervention measures for family caregivers of patients with urostomy, which could play an important role in developing the overall model of family-centered nursing.

Analytical Gradient Using Cluster-in-Molecule RI-MP2 Method for the Geometry Optimizations of Large Systems.

We present an efficient analytical energy gradient algorithm for the cluster-in-molecule resolution-of-identity second-order Møller-Plesset perturbation (CIM-RI-MP2) method based on the Lagrange multiplier method. Our algorithm independently constructs the Lagrangian formalism within each cluster, avoiding the solution of the coupled-perturbed Hartree-Fock (CPHF) equation for the whole system. Due to this feature, the computational cost of the CIM-RI-MP2 gradients is much lower than that of other local MP2 algorithms. Benchmark calculations of several molecules containing up to 312 atoms demonstrate the general applicability of our CIM-RI-MP2 gradient algorithm. The optimized structure of a 244-atom molecule using the CIM-RI-MP2 method with the cc-pVDZ basis set is in good agreement with the corresponding crystal structure. A single-point gradient calculation conducted for a molecular cage containing 972 atoms and 9612 basis functions takes 48 h on 25 nodes, utilizing a total of 600 CPU cores. The present CIM-RI-MP2 gradient program is applicable for obtaining the optimized geometries of large systems with hundreds of atoms.

Identification of a DNA-methylome-based signature for prognosis prediction in driver gene-negative lung adenocarcinoma.

"Driver gene-negative" lung adenocarcinoma (LUAD) was of rare treatment options and a poor prognosis. Presently, for them, few biomarkers are available for stratification analysis to make appropriate treatment strategy. This study aimed to develop a DNA-methylome-based signature to realize the precise risk-stratifying. Here, an Illumina MethylationEPIC Beadchip was applied to obtain differentially methylated CpG sites (DMCs). A four-CpG-based signature, named as TLA, was successfully established, whose prognosis-predicting power was well verified in one internal (n = 78) and other external (n = 110) validation cohorts. Patients with high-risk scores had shorter overall survival (OS) in all cohorts [hazard ratio (HR): 11.79, 5.16 and 2.99, respectively]. Additionally, it can effectively divide patients into low-risk and high-risk groups, with significantly different OS in the diverse subgroups stratified by the standard clinical parameters. As an independent prognostic factor, TLA may assist in improving the nomogram's 5-year OS-predicting ability (AUC 0.756, 95% CI:0.695-0.816), superior to TNM alone (AUC 0.644, 95% CI: 0.590-0.698). Additionally, the relationship of TLA-related genes, TAC1, LHX9, and ALX1, with prognosis and tumour invasion made them serve as potential therapy targets for driver gene-negative LUAD.

Ghrelin and depressive symptoms in patients with first-episode drug-naïve major depressive disorder: The mediating role of hypothalamic-pituitary-adrenal axis.

BACKGROUND: Major depressive disorder (MDD) is one of the global burdens of disease, and its pathogenesis remains unclear. An increasing amount of research indicates that ghrelin regulates mood in patients with MDD. Still, current results are inconsistent, and the mechanisms underlying how ghrelin modulates depressive symptoms are inconclusive, especially in first-episode drug-naïve MDD patients. Therefore, this study aims to investigate the relationship and potential mechanism between ghrelin and first-episode drug-naïve MDD. METHODS: Ninety first-episode drug-naïve MDD patients and 65 healthy controls (HCs) were included. Hamilton Depression Scale (HAMD-17) as a measure of depressive symptoms. Plasma levels of ghrelin and hypothalamic-pituitary-adrenal axis (HPA-axis) hormones were measured in all participants. RESULTS: Compared to HCs, the ghrelin levels were higher in the MDD (p < .001) and still showed significance after covarying for sex, age, and Body Mass Index (BMI). Ghrelin was positively related to corticotropin-releasing-hormone (CRH) levels (r = .867, p < .001), adrenocorticotropic hormone (ACTH) levels (r = .830, p < .001), and cortisol levels (r = .902, p < .001) in partial correlation analysis. In addition, there was a positive correlation between HAMD total score and ghrelin levels (r = .240, p = .026). Other than that, the HAMD total score also had a positive correlation with the CRH (r = .333, p = .002) and cortisol (r = .307, p = .004) levels. Further mediation analysis demonstrated that the relationship between ghrelin and HAMD total score was mediated by CRH (ab-path; ß = .4457, 95% CI = 0.0780-1.0253, c-path; ß = .2447, p = .0260, c'-path; ß = -.2009, p = .3427). CONCLUSIONS: These findings revealed that plasma ghrelin provides a pivotal link to depressive symptoms in first-episode drug-naive MDD patients. CRH mediated the relationship between ghrelin and HAMD total score. It might provide new insights into understanding the pathogenesis of MDD, contributing to intervention and treatment from this approach.

Integrated Metabolomics and Transcriptomics Analyses Highlight the Flavonoid Compounds Response to Alkaline Salt Stress in Glycyrrhiza uralensis Leaves.

Glycyrrhiza uralensis is a saline-alkali-tolerant plant whose aerial parts are rich in flavonoids; however, the role of these flavonoids in saline-alkali tolerance remains unclear. Herein, we performed physiological, metabolomics, and transcriptomics analyses in G. uralensis leaves under alkaline salt stress for different durations. Alkaline salt stress stimulated excessive accumulation of reactive oxygen species and consequently destroyed the cell membrane, causing cell death, and G. uralensis initiated osmotic regulation and the antioxidant system to respond to stress. In total, 803 metabolites, including 244 flavonoids, were detected via metabolomics analysis. Differentially altered metabolites and differentially expressed genes were coenriched in flavonoid-related pathways. Genes such as novel.4890, Glyur001511s00039602, and Glyur000775s00025737 were highly expressed, and flavonoid metabolites such as 2'-hydroxygenistein, apigenin, and 3-O-methylquercetin were upregulated. Thus, flavonoids as nonenzymatic antioxidants play an important role in stress tolerance. These findings provide novel insights into the response of G. uralensis to alkaline salt stress.

Treatment of lung cancer by acupuncture combined with medicine based on pathophysiological mechanism: A review.

Lung cancer is one of the most frequently diagnosed cancers in the world. There are an estimated 2.2 million new cases and 1.79 million deaths each year. Over the past 2 decades, our understanding of disease biology, the use of predictive biomarkers, and improvements in therapeutic approaches have made significant progress and transformed the outcomes of many patients. Treatment is determined by the subtype and stage of the cancer; however, the effect of personalized treatment remains unsatisfactory. The use of Chinese medicines has attracted increasing attention worldwide. Chinese medicine treatment of lung cancer has few side effects, which can effectively prolong the survival expectation of patients and improve their quality of life, and has attracted increasing attention. Based on the pathophysiological mechanism of lung cancer reported in modern medical research, this article explores the efficacy and safety of acupuncture combined with medicine in the treatment of lung cancer.

Topological Data Analysis Combined with High-Throughput Computational Screening of Hydrophobic Metal-Organic Frameworks: Application to the Adsorptive Separation of C3 Components.

The shape and topology of pores have significant impacts on the gas storage properties of nanoporous materials. Metal-organic frameworks (MOFs) are ideal materials with which to tailor to the needs of specific applications, due to properties such as their tunable structure and high specific surface area. It is, therefore, particularly important to develop descriptors that accurately identify the topological features of MOF pores. In this work, a topological data analysis method was used to develop a topological descriptor, based on the pore topology, which was combined with the Extreme Gradient Boosting (XGBoost) algorithm to predict the adsorption performance of MOFs for methane/ethane/propane. The final results show that this descriptor can accurately predict the performance of MOFs, and the introduction of the topological descriptor also significantly improves the accuracy of the model, resulting in an increase of up to 17.55% in the R2 value of the model and a decrease of up to 46.1% in the RMSE, compared to commonly used models that are based on the structural descriptor. The results of this study contribute to a deeper understanding of the relationship between the performance and structure of MOFs and provide useful guidelines and strategies for the design of high-performance separation materials.

Facilely Prepared Carbon Dots as Effective Anode Modifier for Enhanced Performance of Microbial Fuel Cells.

Microbial fuel cells (MFCs) are a promising technology for obtaining energy in wastewater. Effective extracellular electron transfer is one of the key factors for its practical application. In this work, carbon dots (CDs) enriched with oxygen-containing groups on the surface were synthesized as an efficient anode modifier using a simple hydrothermal method and common reactants. The experimental findings indicated that anodes modified with CDs exhibited increased electrical conductivity and greater hydrophilicity. These modifications facilitated increased microorganism loading and contributed to enhancing electrochemical processes within the anode biofilm. The CD-modified MFCs exhibited higher maximum power density (661.1 ± 42.6 mW·m-2) and open-circuit voltage (534.50 ± 6.4 mV), which were significantly better than those of the blank group MFCs (484.1 ± 14.1 mW·m-2 and 447.50 ± 12.1 mV). The use of simple carbon materials to improve the microbial loading on the MFCs anode and the electron transfer between the microbial-electrode may provide a new idea for the design of efficient MFCs.

Block-Correlated Coupled Cluster Theory with up to Four-Pair Correlation for Accurate Static Correlation of Strongly Correlated Systems.

A block-correlated coupled cluster method with up to four-pair correlation based on the generalized valence bond wave function (GVB-BCCC4) is first implemented, which offers an alternative method for electronic structure calculations of strongly correlated systems. We developed some techniques to derive a set of compact and cost-effective equations for GVB-BCCC4, which include the definition of n-block (n = 1-4) Hamiltonian matrices, the combination of excitation operators, and the definition of independent amplitudes. We then applied the GVB-BCCC4 method to investigate several potential energy surfaces of strongly correlated systems with singlet ground states. Our calculations demonstrate that the GVB-BCCC4 method can provide nearly exact static correlation energies as the density matrix renormalization group method (on the basis of the same GVB orbitals). This work highlights the significance of four-pair correlation in quantitative descriptions of static correlation energy for strongly correlated systems.

COLOCdb: a comprehensive resource for multi-model colocalization of complex traits.

Large-scale genome-wide association studies (GWAS) have provided profound insights into complex traits and diseases. Yet, deciphering the fine-scale molecular mechanisms of how genetic variants manifest to cause the phenotypes remains a daunting task. Here, we present COLOCdb (https://ngdc.cncb.ac.cn/colocdb), a comprehensive genetic colocalization database by integrating more than 3000 GWAS summary statistics and 13 types of xQTL to date. By employing two representative approaches for the colocalization analysis, COLOCdb deposits results from three key components: (i) GWAS-xQTL, pair-wise colocalization between GWAS loci and different types of xQTL, (ii) GWAS-GWAS, pair-wise colocalization between the trait-associated genetic loci from GWASs and (iii) xQTL-xQTL, pair-wise colocalization between the genetic loci associated with molecular phenotypes in xQTLs. These results together represent the most comprehensive colocalization analysis, which also greatly expands the list of shared variants with genetic pleiotropy. We expect that COLOCdb can serve as a unique and useful resource in advancing the discovery of new biological mechanisms and benefit future functional studies.

Analysis of the cause of retrolingual obstruction in patients with moderate-severe obstructive sleep apnea.

PURPOSE: To evaluate the percentage of obstructive sleep apnea (OSA) patients with retrolingual obstruction in all moderate-severe OSA patients and the proportions of different causes in all moderate-severe OSA patients with retrolingual obstruction and to discuss the accuracy of the Friedman tongue position (FTP) and retrolingual cross-sectional area (RCSA) in assessing the retrolingual obstruction. METHODS: Two hundred and twenty moderate-severe OSA patients were enrolled. After retrolingual obstruction was diagnosed, the percentage of OSA patients with retrolingual obstruction in all moderate-severe OSA patients was calculated. After that, the different causes of retrolingual obstruction were diagnosed based on different diagnostic criteria, and the proportions of different causes in all moderate-severe OSA patients with retrolingual obstruction were calculated. Finally, the correlations between FTP, RCSA, and apnea-hypopnea index after nasopharyngeal tube insertion (NPT-AHI) were analyzed, and the proportions of different causes of retrolingual obstruction based on different FTP and RCSA were observed. RESULTS: There were 128 patients with retrolingual obstruction, accounting for 58.2% of all moderate-severe OSA patients. In 128 patients with retrolingual obstruction, the proportions of glossoptosis (48.4%), palatal tonsil hypertrophy (28.1%), and lingual hypertrophy (8.6%) were relatively high. Both FTP and RCSA did not correlate with NPT-AHI. The proportion of lingual hypertrophy increased gradually with the increase of FTP and the proportions of glossoptosis in all FTP classifications were high. The patients with RCSA > 180 mm2 were mainly affected by glossoptosis and palatal tonsil hypertrophy, while patients with RCSA ≤ 180 mm2 were mainly affected by lingual hypertrophy. CONCLUSION: The percentage of patients with retrolingual obstruction in all moderate-severe OSA patients is relatively high, mainly glossoptosis, palatal tonsil hypertrophy, and lingual hypertrophy. FTP classification and RCSA can only reflect the retrolingual anatomical stenosis, but cannot fully reflect the retrolingual functional stenosis, especially the presence of glossoptosis.

Role of serum alkaline phosphatase as a potential biomarker of severity and prognosis in intracerebral hemorrhage.

OBJECTIVES: Alkaline phosphatase (ALP) catalyzes the hydrolysis of pyrophosphate and facilitates vascular calcification. We aimed at investigating serum ALP levels in intracerebral hemorrhage (ICH) patients and ascertaining its relationship to severity and prognosis. METHODS: Serum ALP levels from 148 patients and 148 healthy controls were detected. Glasgow coma scale (GCS) score and hematoma volume at admission were recorded to evaluate hemorrhagic severity. Modified Rankin Scale (mRS) score > 2 at 90 days after onset was judged as a poor prognosis. RESULTS: Serum ALP levels in patients with ICH were substantially elevated compared with healthy controls, and were significantly related to hematoma volume and GCS score. Serum ALP levels significantly distinguished ICH patients at risk for unfavorable prognosis. Serum ALP levels > 78.5 U/L in ICH patients may indicated a unfavorable prognosis with 69.1 % sensitivity and 83.6 % specificity, and served as an independent predictor for unfavorable prognosis. CONLUSIONS: Elevated serum ALP levels were intimately connected with increased severity and 90-day unfavorable prognosis in patients with ICH. Serum ALP could be a potential biomarker for severity and prognosis of ICH.

IL-27 Alleviates Airway Inflammation and Airway Hyperresponsiveness in Asthmatic Mice by Targeting the CD39/ATP Axis of Dendritic Cells.

Interleukin-27 receptor (IL-27R) is expressed in a variety of immune cells and structural cells, including dendritic cells. The mechanism of IL-27 in asthma has not been fully elucidated. This study aimed to examine whether IL-27 regulated the CD39/ATP axis of dendritic cells in asthma. Our results showed that in ovalbumin (OVA)-induced asthma mouse model, IL-27Rα-/- asthmatic mice showed increased airway resistance, increased infiltration of inflammatory cells in lung tissue, proliferation of goblet cells, enhanced expression of Muc5 AC around airway epithelium, increased total number of cells and eosinophils, increased levels of total IgE, OVA-IgE, IL-4, IL-5, IL-13 and IL-17 A, and increased expression of transcription factors GATA-3 and RORγt in lung tissue. The expression of CD39 mRNA and protein in the lung tissue of IL-27Rα-/- asthmatic mice decreased, and the expression of NLRP3, ASC and Caspase-1 in NLRP3 inflammasome components increased. The concentration of ATP was significantly increased compared with WT asthmatic mice. In vitro experiments showed that the expression of CD39 in lung dendritic cells of IL-27Rα-/- asthmatic mice decreased, while the expression of NLRP3 inflammasome components NLRP3, ASC and Caspase-1 increased. These findings indicate that IL-27 directly and indirectly regulates immunoinflammatory responses in asthma by acting on dendritic cells CD39/ATP Axis.

Correlation Between Rapid Eye Movement Sleep Duration and Laryngopharyngeal Reflux in Patients with Obstructive Sleep Apnea.

Objectives: The aim of this study was to investigate the correlation between rapid eye movement (REM) sleep duration and laryngopharyngeal reflux (LPR) in patients with obstructive sleep apnea (OSA). Methods: In all, 99 patients with OSA were enrolled in this study, and the correlation between REM sleep duration and the severity of LPR was analyzed after the polysomnography (PSG) and reflux symptom index (RSI) scores were completed. Subsequently, a multiple linear regression analysis was performed to further clarify the factors affecting LPR. Results: Partial correlation analysis showed that the REM sleep duration was positively correlated with the RSI scores (r = 0.236, P = .022) after controlling for apnea-hypopnea index (AHI), body mass index (BMI), lowest oxygen saturation (LSO2), age, and sex. The multiple linear regression analysis indicated that only REM sleep duration was a factor influencing LPR (t = 2.330, P = .022). Conclusions: Our study found a correlation between REM sleep duration and LPR in OSA patients. The shorter the REM sleep duration, the less severe the LPR symptoms.

Perceived stress and severity of depression mediate the association between alexithymia and suicidal ideation in patients with major depressive disorder.

Introduction: Alexithymia and perceived stress have been recognized as risk factors for suicide in patients with major depressive disorder (MDD). However, few studies have been conducted to examine the relationship between these factors. Methods: A cross-sectional study was conducted on 105 MDD patients. Alexithymia was assessed by the 20-Item Toronto Alexithymia Scale (TAS), perceived stress was assessed by the Perceived Stress Scale (PSS), severity of depression was assessed by the 17-item Hamilton Depression Rating Scale (HAMD), and suicidal ideation was assessed by the self-report Beck Scale for Suicide Ideation (SSI). A sequential mediation model was established to test the mediating effects of perceived stress and severity of depression on the association between alexithymia and suicidal ideation. Results: 81 of the 105 participants (77.14 %) had suicidal ideation. Patients with suicidal ideation had greater difficulty in identifying feelings (DIF) (p = 0.046), higher severity of depression (p = 0.005) and perceived stress (p = 0.003). DIF subscale score of TAS was associated with perceived stress (r = 0.292, p = 0.003), severity of depression (r = 0.349, p < 0.001) and suicidal ideation (r = 0.229, p = 0.012). Sequential mediation model showed that perceived stress and severity of depression mediated the effect of DIF on suicidal ideation. Conclusions: This study suggests that perceived stress and severity of depression fully mediate the relationship between difficulty in identifying feelings and suicidal ideation in MDD patients.

Cluster-in-Molecule Local Correlation Method for Dispersion Interactions in Large Systems and Periodic Systems.

ConspectusThe noncovalent interactions, including dispersion interactions, control the structures and stabilities of complex chemical systems, including host-guest complexes and the adsorption process of molecules on the solid surfaces. The density functional theory (DFT) with empirical dispersion correction is now the working horse in many areas of applications. Post-Hartree-Fock (post-HF) methods have been well recognized to provide more accurate descriptions in a systematic way. However, traditional post-HF methods are mainly limited to small- or medium-sized systems, and their applications to periodic condensed phase systems are still very limited due to their expensive computational costs.To extend post-HF calculations to large molecules, the cluster-in-molecule (CIM) local correlation approach has been established, allowing highly accurate electron correlation calculations that are routinely available for very large systems. In the CIM approach, the electron correlation energy of a large molecule could be obtained from electron correlation calculations on a series of clusters, each of which contains a subset of occupied and virtual localized molecular orbitals. The CIM method could be massively and efficiently parallelized on general computer clusters. The CIM method has been implemented at various electron correlation levels, including second-order MoÌ·ller-Plesset perturbation theory (MP2), coupled cluster singles and doubles (CCSD), CCSD with perturbative triples correction [CCSD(T)], etc. The CIM-MP2 energy gradient algorithm was developed and applied to the geometry optimizations of large systems. The CIM method has also been extended to condensed-phase systems under periodic boundary conditions (PBC-CIM). For periodic systems, the correlation energy per unit cell could be evaluated with correlation energy contributions from a series of clusters that are built with localized Wannier functions.CIM-based electron correlation calculations have been employed to investigate a number of chemical problems in which the dispersion interaction is important. CIM-based post-HF methods including CIM domain-based local pair natural orbital (DLPNO) CCSD(T) are applied to compute the relative or binding energies of biological systems or supramolecular complexes, the reaction barrier in a relatively complex chemical reaction. The CIM-MP2 method is used to obtain the optimized geometry of large systems. CIM-based post-HF calculations have also been used to compute the cohesive energies of molecular crystals and adsorption energies of molecules on the solid surfaces. The CIM and its PBC variant are expected to become a powerful theoretical tool for accurate calculations of the energies and structures for a broad range of large systems and condensed-phase systems with significant dispersion interactions.

Base-mediated C-B bond activation of benzylic boronate for the rapid construction of ß-silyl/boryl functionalized 1,1-diarylalkanes from aromatic alkenes.

The effect of tBuOK on the existing state of benzylic boronates in the solution phase has been investigated in detail by NMR analysis and DFT calculations. It was determined that simply using an excess of tBuOK (2.0 equivalents) can result in the full deborylation of benzylic boronates to afford free benzyl potassium species. These mechanistic insights were leveraged for the facile construction of ß-silyl/boryl functionalized 1,1-diarylalkanes from aromatic alkenes via the combination of base-mediated silylboration or diborylation of aromatic alkenes and nucleophilic-type reactions with various electrophiles. Based on further machine-learning-assisted screening, the scope of electrophiles for this transformation can be generalized to the challenging aromatic heterocycles. Late-stage functionalization performed on several drug-relevant molecules generates the highly valuable 1,1-diaryl framework.