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Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor with an ill-defined pathogenesis. DExD box (DDX) family genes are widely distributed and involved in various RNA metabolism and cellular biogenesis; their dysregulation is associated with aberrant cellular processes and malignancies. However, the prognostic significance and expression patterns of the DDX family in PDAC are not fully understood. The present study aimed to explore the clinical value of DDX genes in PDAC. Methods Differentially expressed DDX genes were identified. DDX genes related to prognostic signatures were further investigated using LASSO Cox regression analysis. DDX21 protein expression was analyzed using the UALCAN and human protein atlas (HPA) online tools and confirmed in 40 paired PDAC and normal tissues through Tissue Microarrays (TMA). The independent prognostic significance of DDX21 in PDAC was determined through the construction of nomogram models and calibration curves. The functional roles of DDX21 were investigated using gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Cell proliferation, invasion, and migration were assessed using Cell Counting Kit-8, colony formation, Transwell, and wound healing assays. Results Upregulation of genes related to prognostic signatures (DDX10, DDX21, DDX60, and DDX60L) was significantly associated with poor prognosis of patients with PDAC based on survival and recurrence time. Considering the expression profile and prognostic values of the signature-related genes, DDX21 was finally selected for further exploration. DDX21 was overexpressed significantly at both the mRNA and protein levels in PDAC compared to normal pancreatic tissues. DDX21 expression, pathological stage, and residual tumor were significant independent prognostic indicators in PDAC. Moreover, functional enrichment analysis revealed that Genes co-expressed with DDX21 are predominantly involved in RNA metabolism, helicase activity, ribosome biogenesis, cell cycle, and various cancer-related pathways, such as PI3K/Akt signaling pathway and TGF-β signaling pathway. Furthermore, in vitro experiments confirmed that the knockdown of DDX21 significantly reduced MIA PaCa-2 cell viability, proliferation, migration, and invasion. Conclusions Four signature-related genes could relatively precisely predict the prognosis of patients with PDAC. Specifically, DDX21 upregulation may signal an unfavorable prognosis by negatively affecting the biological properties of PDAC cells. DDX21 may be considered as a candidate therapeutic target in PDAC.

Abstract Introduction Dent disease type I is a rare X-linked recessive renal tubular disease resulting from pathogenic variants in the CLCN5 gene. Due to the rarity of Dent disease type I and the diversity of its phenotypes, its clinical diagnosis is complex and poses a challenge to clinicians. Methods A foetus and a child from a 36-year-old pregnant woman with a birth history of abnormal children were enrolled in this study. Pregnant women undergo amniocentesis for prenatal diagnosis at the gestational age of 12+ 3 weeks. Chromosomal microarray (CMA) analysis and whole-exome sequencing (WES) were employed to investigate the chromosomal copy number and single gene variants. Literature retrieval and data analysis were performed for genotype and phenotype collection analysis. Results No chromosomal abnormalities or CNVs were detected in the entire family through karyotype and familial CMA analyses. WES identified a nonsense pathogenic variant in CLCN5 of the X chromosome, c.1942 C > T (exon 11, NM_000084), which was inherited from his mother, who exhibited regular clinical features. Conclusion This study suggests that children with low-molecular-weight proteinuria and hypercalciuria should undergo prompt genetic testing to exclude Dent disease.

Major depressive disorder (MDD) is the most common psychological disease. To improve the recognition accuracy of MDD, more and more machine learning methods have been proposed to mining EEG features, i.e. typical brain functional patterns and recognition methods that are closely related to depression using resting EEG signals. Most existing methods typically utilize threshold methods to filter weak connections in the brain functional connectivity network (BFCN) and construct quantitative statistical features of brain function to measure the BFCN. However, these thresholds may excessively remove weak connections with functional relevance, which is not conducive to discovering potential hidden patterns in weak connections. In addition, statistical features cannot describe the topological structure features and information network propagation patterns of the brain’s different functional regions. To solve these problems, we propose a novel MDD recognition method based on a multi-granularity graph convolution network (MGGCN). On the one hand, this method applies multiple sets of different thresholds to build a multi-granularity functional neural network, which can remove noise while fully retaining valuable weak connections. On the other hand, this method utilizes graph neural network to learn the topological structure features and brain saliency patterns of changes between brain functional regions on the multi-granularity functional neural network. Experimental results on the benchmark datasets validate the superior performance and time complexity of MGGCN. The analysis shows that as the granularity increases, the connectivity defects in the right frontal(RF) and right temporal (RT) regions, left temporal(LT) and left posterior(LP) regions increase. The brain functional connections in these regions can serve as potential biomarkers for MDD recognition.

Colletotrichum species are the most common cause of maize anthracnose, which often manifests as leaf spots. However, field observations often reveal symptoms similar to those caused by other leaf spot pathogens, such as Curvularia and Bipolaris. In this study, 99 isolates were identified using tissue separation and single-spore isolation techniques. As preliminary measures of species diversity, all 99 isolates were identified morphologically, and the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene sequences were phylogenetically analyzed. Furthermore, 48 representative strains were selected for molecular identification using multi-locus phylogenetic analyses based on five gene loci (ITS, TUB, ACT, GAPDH, and CAL). Finally, 10 species of Colletotrichum isolated from maize leaf spots were identified. Colletotrichum cliviicola was the most dominant species (24.2%), followed by C. fructicola (18.2%), C. karstii (16.1%), C. siamense (13.1%), C. boninense (7.1%), C. kahawae (7.1%), C. brevisporum (6.1%), C. truncatum (5.1%), C. gigasporum (2.0%), and C. gloeosporioides (1.0%). For the first time, pathogenicity tests revealed that C. cliviicola, C. fructicola, C. siamense, C. karstii, and C. truncatum are the causative agents of maize anthracnose. Additionally, C. boninense was identified as an endophytic fungus on healthy maize. In conclusion, this study is the first to identify the pathogen of maize anthracnose in Sichuan Province. It provides valuable insights for accurately diagnosing and managing maize anthracnose.

Ligusticum chuanxiong Hort. is considered an important medicinal herb with extremely high economic value and medicinal value due to its various effects, including anti-oxidation, sedative action, hepatoprotection, and invigorating blood circulation. However, L. chuanxiong cultivation is hampered by various plant diseases, especially the root rot caused by Fusarium solani, hindering the sustainable development of the L. chuanxiong industry. The occurrence of soil-borne diseases is closely linked to imbalances in the microbial community structure. Here, we studied the yields, rhizosphere microbiota, and soil physiochemical characteristics of healthy and diseased L. chuanxiong plants affected by root rot with high-throughput sequencing and microbial network analysis, aiming to explore the relationships between soil environmental factors, microbiomes, and plant health of L. chuanxiong. According to the results, L. chuanxiong root rot significantly decreased the yields, altered microbial community diversity and composition, enriched more pathogenic fungi, recruited some beneficial bacteria, and reduced microbial interaction network stability. The Mantel test showed that soil organic matter and pH were the major environmental factors modulating plant microbiome assembly. The root rot severity was significantly affected by soil physiochemical properties, including organic matter, cation exchange capacity, available nitrogen, phosphorus, potassium, and pH. Furthermore, two differential microbes that have great potential in the biocontrol of L. chuanxiong root rot were dug out in the obtained results, which were the genera Trichoderma and Bacillus. This study provided a theoretical basis for further studies revealing the microecological mechanism of L. chuanxiong root rot and the ecological prevention and control of L. chuanxiong root rot from a microbial ecology perspective.

Virus receptors determine the tissue tropism of viruses and have a certain relationship with the clinical outcomes caused by viral infection, which is of great importance for the identification of virus receptors to understand the infection mechanism of viruses and to develop entry inhibitor. Proximity labeling (PL) is a new technique for studying protein-protein interactions, but it has not yet been applied to the identification of virus receptors or co-receptors. Here, we attempt to identify co-receptor of SARS-CoV-2 by employing TurboID-catalyzed PL. The membrane protein angiotensin-converting enzyme 2 (ACE2) was employed as a bait and conjugated to TurboID, and a A549 cell line with stable expression of ACE2-TurboID was constructed. SARS-CoV-2 pseudovirus were incubated with ACE2-TurboID stably expressed cell lines in the presence of biotin and ATP, which could initiate the catalytic activity of TurboID and tag adjacent endogenous proteins with biotin. Subsequently, the biotinylated proteins were harvested and identified by mass spectrometry. We identified a membrane protein, AXL, that has been functionally shown to mediate SARS-CoV-2 entry into host cells. Our data suggest that PL could be used to identify co-receptors for virus entry.

Abstract Activating transcription factor 6 (ATF6) is an endoplasmic reticulum stress responsive gene. We previously reported that conditional knockout of hepatic ATF6 exacerbated liver metabolic damage by repressing autophagy through mTOR pathway. However, the mechanism by which ATF6 influence liver metabolism has not been well established. Hydrogen sulfide (H2S) is a gaseous signaling molecule that plays an important role in regulating inflammation, and suppress nonalcoholic fatty liver in mice. Based on the previous study, we assumed that ATF6 may regulate H2S production to participate in liver metabolism. In order to clarify the mechanism by which ATF6 regulates H2S synthesis to ameliorate liver steatosis and inflammatory environment, we conducted the present study. We used the liver specific ATF6 knockout mice and fed on high-fat-diet, and found that H2S level was significantly downregulated in hepatic ATF6 knockout mice. Restoring H2S by the administration of slow H2S releasing agent GYY4137 ameliorated the hepatic steatosis and glucose tolerance. ATF6 directly binds to the promoter of cystathionine β synthetase (CBS), an important enzyme in H2S synthesis. Thus, ATF6 could upregulate H2S production through CBS. Sulfhydrated Sirtuin-1 (SIRT1) was downregulated in ATF6 knockout mice. The expression of pro-inflammatory factor IL-17A was upregulated and anti-inflammatory factor IL-10 was downregulated in ATF6 knockout mice. Our results suggest that ATF6 can transcriptionally enhance CBS expression as well as H2S synthesis. ATF6 increases SIRT1 sulfhydration and ameliorates lipogenesis and inflammation in the fatty liver. Therefore, ATF6 could be a novel therapeutic strategy for high-fat diet induced fatty liver metabolic abnormalities.

Clubroot is a major disease and severe threat to Chinese cabbage, and it is caused by the pathogen Plasmodiophora brassicae Woron. This pathogen is an obligate biotrophic protist and can persist in soil in the form of resting spores for more than 18 years, which can easily be transmitted through a number of agents, resulting in significant economic losses to global Chinese cabbage production. Rhizosphere microbiomes play fundamental roles in the occurrence and development of plant diseases. The changes in the rhizosphere microorganisms could reveal the severity of plant diseases and provide the basis for their control. Here, we studied the rhizosphere microbiota after clubroot disease infections with different severities by employing metagenomic sequencing, with the aim of exploring the relationships between plant health, rhizosphere microbial communities, and soil environments; then, we identified potential biomarker microbes of clubroot disease. The results showed that clubroot disease severity significantly affected the microbial community composition and structure of the rhizosphere soil, and microbial functions were also dramatically influenced by it. Four different microbes that had great potential in the biocontrol of clubroot disease were identified from the obtained results; they were the genera Pseudomonas, Gemmatimonas, Sphingomonas, and Nocardioides. Soil pH, organic matter contents, total nitrogen, and cation exchange capacity were the major environmental factors modulating plant microbiome assembly. In addition, microbial environmental information processing was extremely strengthened when the plant was subjected to pathogen invasion, but weakened when the disease became serious. In particular, oxidative phosphorylation and glycerol-1-phosphatase might have critical functions in enhancing Chinese cabbage’s resistance to clubroot disease. This work revealed the interactions and potential mechanisms among Chinese cabbage, soil environmental factors, clubroot disease, and microbial community structure and functions, which may provide a novel foundation for further studies using microbiological or metabolic methods to develop disease-resistant cultivation technologies.

β-thalassemia (β-thal) is the most common monogenic disorder caused by various mutations in the human hemoglobin β (HBB) gene and affecting millions of people worldwide. Electroporation of Cas9 and single-guide RNA (sgRNA)–ribonucleoprotein (RNP) complex-mediated gene targeting in patient-derived hematopoietic stem cells (HSCs), followed by autologous transplantation, holds the promise to cure patients lacking a compatible bone marrow donor. In this study, a universal gene correction method was devised to achieve in situ correction of most types of HBB mutations by using validated CRISPR/sgRNA–RNP complexes and recombinant adeno-associated viral 6 (rAAV6) donor-mediated homology-directed repair (HDR) in HSCs. The gene-edited HSCs exhibited multi-lineage formation abilities, and the expression of β-globin transcripts was restored in differentiated erythroid cells. The method was applied to efficiently correct different mutations in β-thal patient-derived HSCs, and the edited HSCs retained the ability to engraft into the bone marrow of immunodeficient NOD-scid-IL2Rg−/− (NSI) mice. This study provides an efficient and safe approach for targeting HSCs by HDR at the HBB locus, which provides a potential therapeutic approach for treating other types of monogenic diseases in patient-specific HSCs.

Abstract Background Skin cutaneous melanoma (SKCM) is an extremely malignant tumor that is associated with a poor prognosis. LSM2 has been found to be related to different types of tumors; however, its role in SKCM is poorly defined. We aimed to determine the value of LSM2 as a prognostic biomarker for SKCM. Methods The expression profile of LSM2 mRNA was compared between tumor and normal tissues in public databases, such as TCGA, GEO, and BioGPS. LSM2 protein expression was explored using immunohistochemistry (IHC) on a tissue microarray containing 44 SKCM tissues and 8 normal samples collected at our center. Kaplan-Meier analysis was performed to assess the prognostic value of LSM2 expression in patients with SKCM. SKCM cell lines with LSM2 knockdown were used to determine the effects of LSM2. Cell counting kit-8 (CCK8) and colony formation assays were conducted to assess cell proliferation, whereas wound healing and transwell assays were carried out to assess the migration and invasion abilities of SKCM cells. Results LSM2 was more highly expressed at the mRNA and protein levels in SKCM than that in normal skin. Moreover, elevated expression of LSM2 was associated with shorter survival time and early recurrence in patients with SKCM. The in vitro results revealed that the silencing of LSM2 in SKCM cells significantly inhibited cell proliferation, migration, and invasion. Conclusion Overall, LSM2 contributes to malignant status and poor prognosis in patients with SKCM and may be identified as a novel prognostic biomarker and therapeutic target.

Abstract With the introduction of emerging technologies such as cloud computing, the railway communication network has the characteristics of complex structure and blurred boundaries, which leads to a series of security threats including information leakage and malicious access. Specifically, the third-party cloud services are difficult to be supervised, and network traffic is untrustworthy. To ensure system security, we propose a zero-trust security model in this paper. Then, we introduce blockchain and Merkle tree to build a distributed identity storage scheme for guaranteeing reliable, confidential and efficient data updates, and improving authentication efficiency. Furthermore, the proxy was introduced for two-way authentication with cloud servers, so that internal and external threats could be counteracted. Moreover, reputation assessment mechanism has been adopted to reduce the possibility of nodes accessing malicious cloud services. Performance analysis demonstrated that the proposed security model is able to enhance the security, efficiency and stability of the system, and consequently can guarantee the safety and reliability of railway transportation.

ABSTRACTJiangxi Province boasts the second-highest forest coverage in China. Its forests play a crucial role in providing essential ecosystem services and maintaining the ecological health of the region. High-resolution and high-precision forest mapping are significant in the timely and accurate monitoring of dynamic forest changes to support sustainable forest management. This study used Sentinel-2 images from four seasons in the Google Earth Engine (GEE) platform to map forest distribution. Moreover, the classification results were compared and analyzed using different classification algorithms and feature-variable combinations. Based on the overall accuracy, the optimal image seasonality, feature combinations and classification algorithms were selected, and the forest maps of Jiangxi Province were mapped from 2019 to 2021. The accuracy evaluation showed that the winter image classification results had the highest accuracy (above 0.88). The red edge bands carried by Sentinel-2 could effectively improve the classification accuracy. The Random Forest classifier is the optimal classification algorithm for forest mapping in Jiangxi Province. The forest mapping obtained can be used for ecological health assessment and ecosystem function. The study provides a scientific basis for accurate and timely extraction of forest cover and can serve as a valuable resource for forest management planning and future research.

Mesoscale vorticity is an important factor that affects the non-uniform horizontal and vertical distribution of hydrologic elements in the ocean. In this paper, temperature and salinity data from measured mesoscale cold-core eddies during a voyage within a certain sea area are studied, and a synchronous sound field test was conducted on the mesoscale vorticity. Based on the temperature and salinity data, the parabolic equation (PE) method was selected to predict the acoustic field, and the results were compared with the measured propagation loss data of the acoustic field to verify the accuracy and effectiveness of the PE model. The underwater sound propagation characteristics in the mesoscale cold-core eddy environment were then analyzed using the temperature and salinity data retrieved from the voyage. It was found that the convergence area of the acoustic field gradually dispersed with an increase in the depth of the sound source. In a mesoscale eddy environment, when sound waves propagate from inside to outside the eddy, the presence of a cold-core eddy causes the convergence area to shift toward the edge of the eddy, and the deviation gradually decreases with an increase in the depth of the sound source.

Abstract As a highly conserved and ubiquitously expressed serine/threonine kinase, p21-activated kinase 2 (PAK2) participates in diverse biologic events. However, its roles in mouse oocyte meiotic maturation remain unclear. The present study revealed that mouse oocytes depleted of Pak2 were unable to completely progress through meiosis and that a majority were arrested at metaphase I. Pak2 depletion thus prompted MI arrest and induced meiotic chromosome alignment defects in mouse oocytes, in part due to a reduction in polo-like kinase (PLK1). We demonstrated that PAK2’s interaction with PLK1 protected it from degradation by APC/CCdh1, and that it promoted meiotic progression and bipolar spindle formation. Our data collectively display critical functions for PAK2 in meiotic progression and chromosome alignment in mouse oocytes.

The fifth-generation (5G) wireless communication has experienced an upsurge of interest for empowering vertical industries, due to its high data volume, extremely low latency, high reliability, and significant improvement in user experience. Specifically, deploying 5G on high-speed railway (HSR) is critical for the promotion of smart travelling such that passengers can connect to the Internet and utilize the on-board time to continue their usual activities. However, there remains a series of challenges in practical implementation, such as the serious Doppler shift caused by the high mobility, the carriage penetration loss especially in the high-frequency bands, frequent handovers, and economic issues. To address these challenges, we propose three schemes in this article to improve the coverage of 5G networks on the train. In particular, we provide a comprehensive description of each scheme in terms of their network architecture and service establishment procedures. Specifically, the mobile edge computing (MEC) is used as the key technology to provide low-latency services for on-board passengers. Moreover, these three schemes are compared among themselves regarding the quality-of-service, the scalability of service, and the related industry development status. Finally, we discuss various potential research directions and open issues in terms of deploying 5G networks on HSR.

Abstract Background Exenatide is a stable analogue of glucagon-like peptide 1 that can reduce postprandial hyperglycemia and has been utilized as adjunctive therapy for type 1 diabetes mellitus (T1DM). The human umbilical cord is a rich source of MSCs, and human umbilical cord mesenchymal stem cells (hUCMSCs) also show potential to enhance insulin secretion. Here, we aimed to explore the effects of hUCMSCs carrying exenatide in T1DM and further identify the possible mechanisms involved. Methods hUCMSCs were isolated from human umbilical cord tissues, identified, and transduced with recombinant lentivirus carrying exenatide to obtain exenatide-carrying hUCMSCs (hUCMSCs@Ex-4). Results The results showed that hUCMSCs@Ex-4 restored the blood glucose levels and body weight of NOD mice, and repressed immune cell infiltration and islet tissue changes. Additionally, in T1DM mice, treatment with hUCMSCs@Ex-4 reduced the blood glucose levels and promoted repair of islet tissue damage. Moreover, hUCMSCs@Ex-4 attenuated renal tissue lesions in T1DM mice. Applying bioinformatic analysis, the effects of hUCMSCs@Ex-4 were suggested to correlate with decreased abundance of pro-inflammatory intestinal bacteria and increased abundance of anti-inflammatory intestinal bacteria. Conclusion Overall, the study indicated that hUCMSCs carrying exenatide might improve beneficial intestinal microflora abundance and promote islet tissue damage repair, thereby alleviating T1DM.

Abstract Background The like-Smith (LSM) family is a group of RNA-binding proteins involved in RNA metabolism. However, their involvement in tumors, particularly skin cutaneous melanoma (SKCM), is not fully understood. In this study, we focused on the expression profiles and prognostic values of the LSM family in SKCM. Methods Raw data were downloaded from The Cancer Genome Atlas. The expression profile and prognostic value of LSM genes in SKCM were explored using the GEPIA, cBioPortal, and HPA databases. Protein–protein and gene–gene interaction analyses were performed using STRING and GeneMANIA. Enrichment and Cox regression analysis were conducted using R software. The TISIDB database was used to explore the relationship between LSMs and immunomodulators. Receiver operating characteristic curves and nomogram models were constructed to validate prognostic values. Results mRNA and protein expression levels of LSM2, LSM4, and LSM12 were significantly elevated in SKCM. The upregulated mRNA expression of LSM2 (p = 0.0013) and LSM4 (p = 0.0043) was significantly correlated with poor overall survival in patients with SKCM, whereas only LSM2 (p = 0.049) overexpression was markedly associated with worse disease-free survival. LSM2 overexpression was an independent risk factor (p = 0.013) and was confirmed to have a high prognostic value in SKCM using the receiver operating characteristic curve (AUC = 0.942) and nomogram models. All LSM genes were identified as genomic mutations, whereas alteration of LSM2 (p = 0.0153) significantly affected the overall survival in patients with SKCM. Significant correlations were observed between LSM family expression, immune cell infiltration, and immunomodulator. Furthermore, function and pathway enrichment analysis showed that the LSM family was mainly RNA binding proteins and involved in RNA splicing and degradation. Conclusion Expression profiles and prognostic values of LSM in SKCM were inconsistent. Among the LSM family, only LSM2 may serve as a potential poor prognosticator and immunotherapeutic target of SKCM.

Internal solitary waves are commonly present in global oceans, and these waves encounter submarine ridges during their propagation, resulting in breaking. In this study, a two-layer fluid model and the gravity collapsing method were used to simulate the breaking process of internal solitary waves encountering submarine ridges in the laboratory, and particle image velocimetry was used to monitor the flow field. Based on the different roles of motion mechanisms in the wave-breaking process, the breaking types were classified. Moreover, the relationship between the topography, the initial parameters of internal solitary waves, and the breaking types was studied, and the movement parameters during the wave-breaking process were analyzed. The experiments showed that the Iribarren number and Bisw parameter proposed based on the gentle slope breaking process could not effectively classify the breaking types when internal solitary waves encountered submarine ridges because the permeability of the submarine ridges was different from that of gentle slopes, which significantly affected the motion mechanism during the breaking process. The movement parameter γ clearly reflected the roles of different motion mechanisms during the wave-breaking process. Another parameter δ established the relationship between the motion mechanisms and the topography and initial wave parameters.

Abstract Background To determine the predictive values of sperm parameters pre- and post-processing by density gradient centrifugation for clinical pregnancy rates (CPRs) following artificial insemination by husband (AIH) in infertile Chinese couples. Methods A total of 3,522 AIH cycles from 1,918 couples were retrospectively analyzed. The parameters were compared between the pregnant and non-pregnant groups and further between different etiological groups (Male-factor, Both-male-and-female-factor, and Other-factor). Multivariate logistic regression analysis was performed to create models for predicting the CPRs of each etiological group. Results The overall CPR was 13.3%. There were significant improvements for most sperm parameters after DGC. Multivariate logistic regression analysis indicated that, in overall AIH cases, the top parameters significantly influencing the CPR of AIH were pre-STR (OR = 1.037; P = 0.048) and post-VSL (OR = 1.036; P = 0.011). In the Male-factor Group, the top influencing parameters were pre-VCL (OR = 2.096; P = 0.008), pre-LIN (OR = 1.930; P = 0.002) and post-VSL (OR = 1.316; P = 0.023). In the Both-factor Group, the top influencing parameters were pre-VCL (OR = 1.451; P = 0.008) and post-motility (OR = 1.218; P = 0.049). In the Other-factor Group, the top influencing parameters were pre-VAP (OR = 1.715; P = 0.024), pre-STR (OR = 1.20; P = 0.011) and post-VSL (OR = 1.04; P = 0.017). Moreover, receiver operating characteristic analysis showed that the logistic regression models of the Male- and Both-factor Groups had greater powers for prognostic classification than those of other groups. Conclusions This study demonstrated that some sperm parameters have a collinearity relationship in predicting the CPR following AIH. Moreover, the predictive capacity of a multivariate logistic regression model is better than those of individual parameters, especially for the Male- and Both-factor Groups. In these cases, pre-VCL is the common top influencing factor.

Abstract Determining the associated relationship of genotype and phenomenon would benefit the understanding of disease and renew disease intervention means. 14,518 patients who underwent haemoglobin electrophoresis from June 2020 to December 2020 were enrolled in our study, and additional data including sex, age and routine blood examination results were collected. We focused on individuals with normal red blood cell indices and no common thalassemia pathogenic mutation and selected three groups for the following study: the control group (2.5% ≤ HbA2 ≤ 3.5%), the HbA2 under 2.5 group (HbA2

BackgroundDietary behaviors and cardiovascular disease are two major health issues that have attracted a lot of attention from researchers worldwide. In this study, we aimed to provide a comprehensive analysis of the publication trends, authorship patterns, institutional affiliations, country/region contributions, journal outlets, highly cited documents, and keyword clusters in the field of dietary behaviors and cardiovascular disease research over the past two decades.MethodsWe conducted a systematic literature review of peer-reviewed articles published from 2002 to 2022 in the Web of Science Core Collection database. We extracted and analyzed data on the annual publication volume, authorship patterns, institutional affiliations, country/region contributions, journal outlets, highly cited documents, and keyword clusters using bibliometric methods and visualization tools.ResultsOur study analyzed 3,904 articles, including 702 reviews and 3,202 research articles. The results revealed a continuous increase in the number of publications in this field over the past two decades. The top 10 authors, institutions, and countries/regions with the highest publication output were identified, indicating the leading contributors to this field. Moreover, the most frequently cited documents and highly clustered keywords were identified, providing insights into the research themes and topics in this field.ConclusionOur study provides a comprehensive analysis of the publication trends, authorship patterns, institutional affiliations, country/region contributions, journal outlets, highly cited documents, and keyword clusters in the field of dietary behaviors and cardiovascular disease research over the past two decades. The findings provide valuable information for researchers, policymakers, and stakeholders to understand the research landscape, identify research gaps, and develop future research directions in this field.

Since multimodal emotion classification in different human states has rarely been studied, this paper explores the emotional mechanisms of the brain functional connectivity networks after emotional stimulation. We devise a multimodal emotion classification method fusing a brain functional connectivity network based on electroencephalography (EEG) and eye gaze (ECFCEG) to study emotional mechanisms. First, the nonlinear phase lag index (PLI) and phase-locked value (PLV) are calculated to construct the multiband brain functional connectivity networks, which are then converted into binary brain networks, and the seven features of the binary brain networks are extracted. At the same time, the features of the eye gaze signals are extracted. Then, a fusion algorithm called kernel canonical correlation analysis, based on feature level and randomization (FRKCCA), is executed for feature-level fusion (FLF) of brain functional connectivity networks and eye gaze. Finally, support vector machines (SVMs) are utilized to classify positive and negative emotions in multiple frequency bands with single modal features and multimodal features. The experimental results demonstrate that multimodal complementary representation properties can effectively improve the accuracy of emotion classification, achieving a classification accuracy of 91.32±1.81%. The classification accuracy of pupil diameter in the valence dimension is higher than that of additional features. In addition, the average emotion classification effect of the valence dimension is preferable to that of arousal. Our findings demonstrate that the brain functional connectivity networks of the right brain exhibit a deficiency. In particular, the information processing ability of the right temporal (RT) and right posterior (RP) regions is weak in the low frequency after emotional stimulation; Conversely, phase synchronization of the brain functional connectivity networks based on PLI is stronger than that of PLV.

Chlamydia trachomatis (CT) infection is the most prevalent sexually transmitted bacterial disease worldwide. However, unlike that in female infertility, the role of CT infection in male infertility remains controversial. The objective of this retrospective study was to explore the impacts of CT infection in the genital tract on sperm quality, sperm acrosin activity, antisperm antibody levels, and inflammation in a large cohort of infertile males in China. A total of 7154 semen samples were collected from infertile male subjects, 416 of whom were CT positive (CT+ group) and 6738 of whom were CT negative (CT− group), in our hospital between January 2016 and December 2018. Routine semen parameters (semen volume, pH, sperm concentration, viability, motility, morphology, etc.), granulocyte elastase levels, antisperm antibody levels, and sperm acrosin activity were compared between the CT+ and CT− groups. Our results showed that CT infection was significantly correlated with an abnormally low semen volume, as well as an increased white blood cell count and granulocyte elastase level (all P < 0.05) in the semen of infertile males; other routine semen parameters were not negatively impacted. The antisperm antibody level and sperm acrosin activity were not affected by CT infection. These findings suggested that CT infection might contribute to inflammation and hypospermia but does not impair sperm viability, motility morphology, and acrosin activity or generate antisperm antibodies in the infertile males of China.

Abstract Background Roberts syndrome (RBS) is a rare autosomal recessive disorder caused by variations in the ESCO2 gene; however, prenatal diagnosis of RBS has never been reported in Chinese families. Additionally, fetal-specific phenotypic characteristics associated with ESCO2 variants have not been reported. Case presentation A fetus in a healthy, nonconsanguineous Chinese family with multiple serious congenital malformations was diagnosed prenatally. Two consecutive fetuses in this family presented with tetraphocomelia, growth restriction, cleft lip and palate bilaterally, and other abnormalities. The main phenotypic characteristics of this case were strongly suspected to be associated with RBS. Finally, whole exome sequence analysis revealed the insertion of a homozygous base pair in exon 6 of the ESCO2 gene (NM_001017420.3, c.1111insA, NP_001017420.1, p.Thr371fs). Both of the couples were heterozygous carriers for this variant. Conclusion We are the first to report a prenatal case of RBS diagnosed in a Chinese family. Here, we have confirmed that the rare variant is a definite pathogenic variant, and we provide detailed phenotypic characteristics for the prenatal diagnosis of RBS due to this causative variant.

Supercapacitors became more and more important recently in the area of energy storage and conversion. Their large power deliveries abilities, high stability and environmental friendliness characteristics draw tremendous attention in high-power applications such as public transit networks. Carbonaceous materials with unique surface and electrochemical properties were widely used in supercapacitors as electrode materials. This review focuses on the developments in supercapacitor electrodes made from carbonaceous materials recently, their working principle and evaluation parameters were summarized briefly. The preparation methods and electrochemical properties of different carbonaceous materials were compared and classified. It was found that the surface situation (e.g., porous structure, hydrophilic) of carbonaceous materials strongly affect the electrochemical performances of supercapacitor. So far, active carbons would be the most applicable carbonaceous electrode materials owing to their good chemical stability and conductivity, extensive accessibility inexpensiveness. But their energy densities still fall behind practical demands. Both theoretical calculations and experimental studies show that surface modification and doping of carbonaceous materials can not only optimize their pore size, structure, conductivity and surface properties, but also can introduce extra pseudocapacitance into these materials. Considering global environmental pollution and energy shortage problems nowadays, we sincerely suggested that future work should focus on domestic, medical and industrial wastes residues derived carbonaceous materials and scaled production process such as reactors and exhaust gas treatment.

Abstract Background The quality of the early embryo is vital to embryonic development and implantation. As a highly conserved serine/threonine kinase, p21-activated kinase 2 (Pak2) participates in diverse biologic processes, especially in cytoskeleton remodeling and cell apoptosis. In mice, Pak2 knock out and endothelial depletion of Pak2 showed embryonic lethality. However, the role of Pak2 in preimplantation embryos remains unelucidated. Methods In the present work, Pak2 was reduced using a specific small interfering RNA in early mouse embryos, validating the unique roles of Pak2 in spindle assembly and DNA repair during mice early embryonic development. We also employed immunoblotting, immunostaining, in vitro fertilization (IVF) and image quantification analyses to test the Pak2 knockdown on the embryonic development progression, spindle assembly, chromosome alignment, oxidative stress, DNA lesions and blastocyst cell apoptosis. Areas in chromatin with γH2AX were detected by immunofluorescence microscopy and serve as a biomarker of DNA damages. Results We found that Pak2 knockdown significantly reduced blastocyst formation of early embryos. In addition, Pak2 reduction led to dramatically increased abnormal spindle assembly and chromosomal aberrations in the embryos. We noted the overproduction of reactive oxygen species (ROS) with Pak2 knockdown in embryos. In response to DNA double strand breaks (DSBs), the histone protein H2AX is specifically phosphorylated at serine139 to generate γH2AX, which is used to quantitative DSBs. In this research, Pak2 knockdown also resulted in the accumulation of phosphorylated γH2AX, indicative of increased embryonic DNA damage. Commensurate with this, a significantly augmented rate of blastocyst cell apoptosis was detected in Pak2-KD embryos compared to their controls. Conclusions Collectively, our data suggest that Pak2 may serve as an important regulator of spindle assembly and DNA repair, and thus participate in the development of early mouse embryos.

Abstract Background Indian Hedgehog (IHH), an important cell signaling protein, plays a key regulatory role in development of cartilage and chondrogenesis. Earlier studies have shown that heterozygous missense mutations in IHH gene may cause brachydactyly type A1 (BDA1), an autosomal dominant inheritance disease characterized by apparent shortness or absence of the middle phalanges of all digits. MicroRNAs (miRNAs) have been found to be significant post-transcriptional regulators of gene expression and significantly influence the process of bone-development. Therefore, it is possible that miRNAs are involved in the mechanism underlying the development of BDA1. However, the relationship between miRNAs and the pathogenesis of BDA1 remains unclear. Methods In this study, we used microarray-based miRNA profiling to investigate the role of miRNAs in BDA1 by characterization of differentially expressed miRNAs in C3H10T1/2 cell line induced by wild type (WT) and p.E95K mutant (MT) IHH signaling. Results Our results identified 6 differentially expressed miRNAs between WT and control (CT) group and 5 differentially expressed miRNAs between MT and CT groups. In particular, miR-135a-1-3p was found to be a significantly differentially expressed miRNA between WT and CT group. Results of dual-luciferase reporter gene experiment successfully discovered Hoxd10 was one of the target gene of miR-135a-1-3p. Additionally, our pathway analysis revealed that the targets of these miRNAs of interest were highly involved with Runx1/2, Notch and collagen-related pathways. Conclusions Taken together, our findings provided important clue for future study of the process of miRNA-regulation in IHH signaling and novel insights into the regulatory role of miRNA in pathogenesis of BDA1.

Abstract Background Polyethylene glycol loxenatide (PEX-168) is a new antidiabetic drug; as such, there are not yet any reports on its weight loss effect. Therefore, this trial was designed to investigate the effect of PEX-168 on simple obese mice. Methods Thirty healthy male C57BL/6 mice were randomly selected and divided into a control group (NC) and an obesity model group. The high-fat diet-induced simple obesity mice were divided into a model control group (HF) and three intervention groups. The intervention groups were injected with different doses of PEX-168 intraperitoneally once a week for 12 weeks (low (LD), medium (MD) and high (HD)). Fasting blood glucose (FBG), body weight and food intake were measured from 1 to 12 weeks after PEX-168 injection. The serum insulin (INS), C-reactive protein (CRP), chemerin and omentin levels were measured after 12 weeks. Results Compared with the HF group, the low dose of PEX-168 reduced the body weight of the mice in a short period of time (8 weeks), and the mice in the MD and HD groups showed a significant decrease in body weight (P < 0.05). The low dose of PEX-168 could effectively improve the blood glucose and homeostasis model assessment of insulin resistance (Homa-IR) of the mice (FBG P < 0.05 INS, Homa-IR P < 0.001), but there was no significant difference between different doses (P > 0.05). CRP levels in the MD and HD groups were significantly improved (P < 0.05). The levels of serum chemerin and omentin in the intervention groups were also significantly improved (P < 0.01), but there was no significant difference between the different doses (P > 0.05). Conclusions PEX-168 significantly reduced the body weight of simple obese mice and improved the insulin resistance. PEX-168 may regulate the expression of chemerin and omentin through its hypoglycaemic effect, and the weight-reducing effect of PEX-168 is unlikely to be the reason for the changes in both.

Abstract Noninvasive prenatal testing (NIPT) for single gene disorders remains challenging. One approach that allows for accurate detection of the slight increase of the maternally inherited allele is the relative haplotype dosage (RHDO) analysis, which requires the construction of parental haplotypes. Recently, the nanopore sequencing technologies have become available and may be an ideal tool for direct construction of haplotypes. Here, we explored the feasibility of combining nanopore sequencing with the RHDO analysis in NIPT of β-thalassemia. Thirteen families at risk for β-thalassemia were recruited. Targeted region of parental genomic DNA was amplified by long-range PCR of 10 kb and 20 kb amplicons. Parental haplotypes were constructed using nanopore sequencing and next generation sequencing data. Fetal inheritance of parental haplotypes was classified by the RHDO analysis using data from maternal plasma DNA sequencing. Haplotype phasing was achieved in 12 families using data from 10 kb library. While data from the 20 kb library gave a better performance that haplotype phasing was achieved in all 13 families. Fetal status was correctly classified in 12 out of 13 families. Thus, targeted nanopore sequencing combined with the RHDO analysis is feasible to NIPT for β-thalassemia.

Abstract Background Obesity is a globally increasing health epidemic requiring early lifestyle intervention. Our main objective was to examine the effectiveness of companion-intensive multi-aspect weight management (CIMWM) in Chinese adults with obesity. Methods In this 6-month, prospective, open-label, multicenter, randomized controlled clinical trial, we recruited 272 obese adults aged 18–50 years with a body mass index (BMI) ≥ 28.0 kg/m2 and capable of using smartphones. CIMWM (n = 136) offered both daily online instructions and monthly face-to-face guidance by physicians, dietitians, and health managers along with the provision of meal replacements in the first 3 months. Traditional multi-aspect weight management (TMWM, n = 136) provided monthly face-to-face guidance by the same panel of professionals and the same meal replacements as CIMWM group, but required subjects to complete daily self-monitoring instead of offering daily online instructions. Body composition and metabolic parameters were assessed at baseline, 1, 2, 3, and 6 months by physicians. The primary outcomes were clinically-significant weight loss and changes in BMI and body composition. Results Participants in both groups showed significantly reduced BMI, body fat mass (BFM), visceral fat area (VFA), and HOMA-IR (p

Abstract To elucidate the symptoms and pathogens diversity of corn Fusarium sheath rot (CFSR), diseased samples were collected from 21 county-level regions in 12 prefecture-level districts of Sichuan Province from 2015 to 2018 in the present study. In the field, two symptom types appeared including small black spots with a linear distribution and wet blotches with a tawny or brown color. One hundred thirty-seven Fusarium isolates were identified based on morphological characteristics and phylogenetic analysis (EF1-α), and Koch’s postulates were also assessed. The results identified the isolates as 8 species in the Fusarium genus, including F. verticillioides, F. proliferatum, F. fujikuroi, F. asiaticum, F. equiseti, F. meridionale, F. graminearum and F. oxysporum, with isolation frequencies of 30.00, 22.67, 15.33, 7.33, 6.00, 5.33, 3.33 and 1.33%, respectively. Fusarium verticillioides and F. proliferatum were the dominant and subdominant species, respectively. Two or more Fusarium species such as F. verticillioides and F. proliferatum were simultaneously identified at a mixed infection rate of 14.67% in the present study. The pathogenicity test results showed that F. proliferatum and F. fujikuroi exhibited the highest virulence, with average disease indices of 30.28 ± 2.87 and 28.06 ± 1.96, followed by F. equiseti and F. verticillioides, with disease indices of 21.48 ± 2.14 and 16.21 ± 1.84, respectively. Fusarium asiaticum, F. graminearum and F. meridonale showed lower virulence, with disease indices of 13.80 ± 2.07, 11.57 ± 2.40 and 13.89 ± 2.49, respectively. Finally, F. orysporum presented the lowest virulence in CFSR, with a disease index of 10.14 ± 1.20. To the best of our knowledge, this is the first report of F. fujikuroi, F. meridionale and F. asiaticum as CFSR pathogens in China.

Reactivation of γ-globin expression is a promising therapeutic approach for β-hemoglobinopathies. Here, we propose a novel Cas9/AAV6-mediated genome editing strategy for the treatment of β-thalassemia: Natural HPFH mutations −113A > G, −114C > T, −117G>A, −175T > C, −195C > G, and −198T > C were introduced by homologous recombination following disruption of BCL11A binding sites in HBG1/HBG2 promoters. Precise on-target editing and significantly increased γ-globin expression during erythroid differentiation were observed in both HUDEP-2 cells and primary HSPCs from β-thalassemia major patients. Moreover, edited HSPCs maintained the capacity for long-term hematopoietic reconstitution in B-NDG hTHPO mice. This study provides evidence of the effectiveness of introducing naturally occurring HPFH mutations as a genetic therapy for β-thalassemia.

Abstract Background Gitelman syndrome is a rare salt-losing renal tubular disorder associated with mutation of SLC12A3 gene, which encodes the Na-Cl co-transporter (NCCT). Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and renin-angiotensin-aldosterone system (RAAS) activation. Different SLC12A3 variants may lead to phenotypic variability and severity. Methods In this study, we reported the clinical features and genetic analysis of a Chinese pedigree diagnosed with Gitelman syndrome. Results The proband exhibited hypokalaemia, hypomagnesemia, metabolic alkalosis, but hypercalciuria and kidney stone formation. The increased urinary calcium excretion made it confused to Bartter syndrome. The persistent renal potassium wasting resulted in renal tubular lesions, and might affect urinary calcium reabsorption and excretion. Genetic analysis revealed mutations of SLC12A3 gene with c.433C > T (p.Arg145Cys), c.1077C > G (p.Asn359Lys), and c.1666C > T (p.Pro556Ser). Potential alterations of structure and function of NCCT protein due to those genetic variations of SLC12A3 are predicted. Interestingly, one sibling of the proband carried the same mutant sites and exhibited similar clinical features with milder phenotypes of hypokalemia and hypomagnesemia, but hypocalciuria rather than hypercalciuria. Family members with at least one wild type copy of SLC12A3 had normal biochemistry. With administration of spironolactone, potassium chloride and magnesium supplement, the serum potassium and magnesium were maintained within normal ranges. Conclusions In this study, we identified compound mutations of SLC12A3 associated with varieties of clinical features. Further efforts are needed to investigate the diversity in clinical manifestations of Gitelman syndrome and its correlation with specific SLC12A3 mutations.

Abstract Background β-Thalassaemia is a clinically common cause of hereditary haemolytic anaemia stemming from mutations in important functional regions of the β-globin gene. The rapid development of gene editing technology and induced pluripotent stem cell (iPSC)-derived haematopoietic stem cell (HSC) transplantation has provided new methods for curing this disease. Methods Genetically corrected β-thalassaemia (homozygous 41/42 deletion) iPSCs that were previously established in our laboratory were induced to differentiate into HSCs, which were transplanted into a mouse model of IVS2–654 β-thalassaemia (B6;129P2-Hbb tm2Unc /J mice) after administration of an appropriate nonmyeloablative conditioning regimen. We also investigated the safety of this method by detecting the incidence of tumour formation in these mice after transplantation. Results The combination of 25 mg/kg busulfan and 50 mg/(kg day) cyclophosphamide is an ideal nonmyeloablative protocol before transplantation. Genetically corrected β-thalassaemic HSCs survived and differentiated in nonmyeloablated thalassaemia mice. No tumour formation was observed in the mice for 10 weeks after transplantation. Conclusion Our study provides evidence that the transplantation of genetically corrected, patient-specific iPSCs could be used to cure genetic diseases, such as β-thalassaemia major.

In this article, we analyze the signal-to-interference ratio (SIR) coverage probability of a multi-cell downlink system with random traffic arrivals. Based on a theoretical model, in which the base stations (BSs) and devices are deployed as independent Poisson point processes (PPPs), we first present the sufficient and necessary conditions of the ε-stable region for the queueing system. Then, by taking into account the impact of spatially queueing interactions among BSs, we focus on the steady status of the queues and introduce a two-queue-length approximated model for the system. Specifically, in the studied new model, the BSs are separated into two sets in the steady state: the long-queue BS set and the short-queue BS set. The locations of the former are modeled by a Neyman-Scott process and those of the latter are modeled as a residual hole process. By applying the first-order statistic approximation, we further approximate the hole process by a homogeneous PPP with the same density. To model the deployment of the BSs precisely, the related parameters in the approximated model are fitted. Using tools from stochastic geometry and queueing theory, we derive the SIR coverage probability in the steady state. An iterative algorithm is proposed to calculate the active probability of the BSs. To reduce the computational complexity, Beta distribution is applied to approximate the probability density function of the service rate in each iteration of the algorithm. Finally, the effect of the fitting parameters and the accuracy of our analysis are presented via Monte Carlo simulations.

Background: Lung adenocarcinoma (LUAD) represents one of the highest incidence rates worldwide. Hypoxia is a significant biomarker associated with poor prognosis of LUAD. However, there are no definitive markers of hypoxia-related long non-coding RNAs (lncRNAs) in LUAD.Methods: From The Cancer Genome Atlas (TCGA) and the Molecular Signatures Database (MSigDB), we acquired the expression of hypoxia-related lncRNAs and corresponding clinical information of LUAD patients. The hypoxia-related prognostic model was constructed by univariable COX regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariable Cox regression analysis. To assess the performance of the model, the Kaplan–Meier (KM) survival and receiver operating characteristic (ROC) curve analyses were performed.Results: We found seven lncRNAs, AC022613.1, AC026355.1, GSEC, LINC00941, NKILA, HSPC324, and MYO16-AS1, as biomarkers of the potential hypoxia-related prognostic signature. In the low-risk group, patients had a better overall survival (OS). In addition, the results of ROC analysis indicated that the risk score predicted LUAD prognosis exactly. Furthermore, combining the expression of lncRNAs with clinical features, two predictive nomograms were constructed, which could accurately predict OS and had high clinical application value.Conclusion: In summary, the seven-lncRNA prognostic signature related to hypoxia might be useful in predicting clinical outcomes and provided new molecular targets for the research of LUAD patients.

Background: Male carriers of complex chromosomal rearrangements (CCRs) may have decreased fertility and usually present with azoospermia, oligospermia or teratospermia.Methods: High-resolution karyotype analysis using G-banding on peripheral blood lymphocytes was performed in an azoospermic male. Copy number variations (CNVs) were detected by chromosomal microarray analysis, and genetic variations were determined by long-read nanopore sequencing with Sanger sequencing for breakpoint confirmation.Results: The karyotype of the patient was 46,XY,t(4;21)(p11;p11),t(5;6;14)(p13q22;p22q22;q22), which did not involve CNVs with clinical significance. Twelve breakpoints in chromosomes 5, 6, and 14 were found by long-read nanopore sequencing. Reports on 17 males carrying CCRs with azoospermia were also reviewed.Conclusion: The extent of asynaptic regions in synaptonemal complexes during pachytene and the disruption of genes involved in male gametogenesis may cause azoospermia in CCR carriers.

Extracellular vesicles (EVs) have been identified as cell-cell communication agents, and EVs derived from mesenchymal stem cells (MSCs) exhibit therapeutic effects similar to those of the cells of origin. Precipitation methods have been used extensively for EV harvests, such as UC- (ultracentrifugation-) or PEG- (polyethylene glycol-) based methods, and the difference in EVs derived from MSCs by UC and PEG is not fully understood. We harvested EVs from amniotic fluid MSCs (AF-MSCs) by UC- or PEG-based precipitation methods and conducted a comparison study of those EVs derived by the two methods: output, RNA, and protein expression of EVs and EV biological reaction in a THP-1-cell model of LPS induction, which was considered an infection model. There was no difference in morphology, size, or specific marker-positive ratio of PEG-EVs and UC-EVs, but PEG obtained more EV particles, protein, and RNA than the UC method. In our THP-1 model of LPS induction, MSC-EVs did not lead to a change in protein expression but inhibited the LPS-induced increase in cytokine secretion. UC-EVs were more effective for TNF-α inhibition, and PEG-EVs were more effective for IL10 inhibition. Thus, our findings provide evidence that PEG-based precipitation is a more efficient mesenchymal stem cell-extracellular vesicle-derived method than UC.

Background. X-linked adrenoleukodystrophy (ALD) is an inherited peroxisomal metabolism disorder, resulting from the loss-of-function mutation of ATP-binding cassette protein subfamily D1 (ABCD1) gene. The dysfunction of ALD protein, a peroxisomal ATP-binding cassette transporter, results in the excessive saturated very long-chain fatty acids (VLCFAs) accumulation in organs including the brain, spine, and adrenal cortex. X-ALD is characterized as the childhood, adolescent, adult cerebral ALD, adrenomyeloneuropathy (AMN), adrenal insufficiency, and asymptomatic phenotypes, exhibiting a high variety of clinical neurological manifestations with or without adrenocortical insufficiency. Results. In this study, we reported two cases of X-ALD, which were first diagnosed as adrenal insufficiency (Addison’s disease) and treated with adrenocortical supplement. However, both of the cases progressed as neurological symptoms and signs after decades. Elevated VLCFAs level, brain MRI scan, and genetic analysis confirmed final diagnosis. In addition, we identified two novel mutations of ABCD1 gene, NM_000033.3 (ABCD1): c.874_876delGAG (p.Glu292del) and NM_000033.3 (ABCD1): c.96_97delCT (p.Tyr33Profs∗161), in exon 1 of ABCD1 gene. Sanger sequencing confirmed that the proband’s mother of the first case was heterozygous carrying the same variant. Adrenal insufficiency-only type is very rare; however, it may be the starting performance of X-ALD. In addition, we summarized reported mutation sites and clinical manifestations to investigate the correlationship of phenotype-genotype of X-ALD. Conclusions. The early warning manifestations should be noticed, and the probability of X-ALD should be considered. This report could be beneficial for the early diagnosis and genetic counseling for patients with X-ALD.

South Asia, one of the most important food producing regions in the world, is facing a significant threat to food grain production under the influence of extreme high temperatures. Furthermore, the probability of simultaneous trends in extreme precipitation patterns and extreme heat conditions, which can have compounding effects on crops, is a likelihood in South Asia. In this study, we found complex relationships between extreme heat and precipitation patterns, as well as compound effects on major crops (rice and wheat) in South Asia. We also employed event coincidence analysis (ECA) to quantify the likelihood of simultaneous temperature and crop extremes. We used the Enhanced Vegetation Index (EVI) as the primary data to evaluate the distinct responses of major crops to weather extremes. Our results suggest that while the probability of simultaneous extreme events is small, most regions of South Asia (more than half) have experienced extreme events. The regulatory effect of precipitation on heat stress is very unevenly distributed in South Asia. The harm caused by a wet year at high temperature is far greater than that during a dry year, although the probability of a dry year is greater than that of a wet year. For the growing seasons, the highest significant event coincidence rates at a low EVI were found for both high- and low-temperature extremes. The regions that responded positively to EVI at extreme temperatures were mainly concentrated in irrigated farmland, and the regions that responded negatively to EVI at extreme temperatures were mostly in the mountains and other high-altitude regions. Implications can guide crop adaptation interventions in response to these climate influences.

Psychological factors can modulate the hypothalamic–pituitary–adrenal (HPA) axis activity toward stressors. Animal studies demonstrated that uncontrollability was one critical factor associated with HPA axis stress response, but the results in human studies were inconsistent. The current study adopted a standardized laboratory stress induction procedure, the Trier Social Stress Test (the TSST), as the stressor to regulate the objective controllability level, and young adult participants were asked to rate their subjectively perceived control level toward the stressor and measured their cortisol stress responses (N=54; 19 females and 35 males) to address this concern. Results showed that participants’ perceived control on the TSST was related to the cortisol stress response. In other words, under the stress of a certain objective controllability level, the lower the subjectively perceived control level, the greater the HPA axis response. This finding suggested that, in addition to objective controllability, subjectively perceived control is a psychological factor that regulates activation of the HPA axis in young adults.

ZBTB7A plays important roles in several biological processes, including silencing of the fetal γ-globin genes, hematopoiesis, primed-to-naive transition, etc. Meanwhile, it is also associated with Oncogenic transformation and tumor progression. However, the mechanism of ZBTB7A function is not fully understood yet. Here, we generated a homozygous ZBTB7A knockout human induced pluripotent stem cell (iPSC) line, GZHMCi007-A by the CRISPR/Cas9-mediated homology-dependent DNA repair method. The iPSCs of ZBTB7A-/- established by us is a powerful tool for related research.

Abstract Background Colchicine is a clinical medicine used for relief from gout and familial Mediterranean fever. Because of its toxic effects, intravenous injection of colchicine has been banned, but it is still widely administered orally. We assayed the toxic effects of colchicine in cultured primary chorionic villus cells and amniotic fluid cells to interpret its influence on the placenta and foetus. Methods Bright field record and cell count kit 8 were used to value cell viability. Flow cytometer was used to identify cells markers, cell cycle and cell apoptosis. G-banding was used for karyotype analysis for sample genetic and drug effect evaluation. Results Chorionic villus cells and amniotic fluid cells were characterized as mesenchymal cells that share most cell surface markers and have a similar response to colchicine. Colchicine did not induce a decline in cell viability at low concentrations but suppressed cell proliferation by arresting the cell cycle in the G2/M phase and increased the risk of tetraploid generation in a small subset of cases. Conclusions Our study revealed the results of a colchicine-induced toxicity test in prenatal cells and determined the anti-mitotic biologically functional dose and manner of administration that might reduce the risk of tetraploid generation.

Abstract Background Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ~ 30% of patients with breast cancer. However, aberrant DNA methylation alterations are frequent events during breast cancer progression and acquisition of chemoresistance. We aimed to characterize the inter- and intra-tumor methylation heterogeneity (MH) in breast cancer following NAC. Methods DNA methylation profiles of spatially separated regions of breast tumors before and after NAC treatment were investigated using high-density methylation microarray. Methylation levels of genes of interest were further examined using multiplexed MethyLight droplet digital PCR (ddPCR). Results We have discovered different levels of intra-tumor MH in breast cancer patients. Moreover, NAC dramatically altered the methylation profiles and such changes were highly heterogeneous between the patients. Despite the high inter-patient heterogeneity, we identified that stem cell quiescence-associated genes ALDH1L1, HOPX, WNT5A and SOX9 were convergently hypomethylated across all the samples after NAC treatment. Furthermore, by using MethyLight ddPCR, we verified that the methylation levels of these 4 genes were significantly lower in breast tumor samples after NAC than those before NAC. Conclusions Our study has revealed that NAC dramatically alters epigenetic heterogeneity in breast cancer and induces convergent hypomethylation of stem cell quiescence-associated genes, ALDH1L1, HOPX, WNT5A and SOX9, which can potentially be developed as therapeutic targets or biomarkers for chemoresistance.

Background: To determine the independent prognostic factors and develop a multivariate logistic regression model for predicting successful pregnancy following artificial insemination by husband (AIH) in infertile Chinese couples.Methods: A total of 3,015 AIH cycles with superovulation from 1,853 infertile Chinese couples were retrospectively analyzed. The clinical characteristics and sperm parameters were compared between the pregnant and non-pregnant groups. Multivariate logistic regression analysis was performed to remove the confounding factors and create an equation to predict the successful pregnancy. Receiver operating characteristic (ROC) curves were constructed for evaluating the abilities for prognostic classification of the independent predictors and the equation.Results: The overall pregnancy rate was 13.0%. The pregnancy rate of double intrauterine insemination (IUI) (18.9%) was significantly higher than that of single IUI (11.4%). The pregnancy rate of the stimulated cycle (14.4%) was significantly higher than that of the natural cycle (9.0%). The pregnancy rates of the age groups

The deletions of the long arm of chromosome 14 involving the 14q24-q32 region have been identified as deletion 14q (del 14q) syndrome, but were rarely reported. The patients with del 14q syndrome are observed a peculiar facial appearance and neurological defects, but the molecular mechanisms were not clear. Here we generated a human iPSC line from the patient’s amniotic fluid cells with 24 Mb deletion in 14q24.3q32.31 which will serve as useful tools for studying the mechanism of del 14q syndrome and the genes involved, which will provide useful basic theory of prenatal diagnosis.

Mutations in the LPL gene lead to familial hypertriglyceridemia (FHTG) . We have previously generated an iPSC line (AHQUi001-A) from a FHTG patient with a heterozygous p.C310R (c.928 T > C) mutation in the LPL gene. Here we genetically corrected the C310R mutation in the LPL gene using CRISPR/Cas9 technology to generate AHQUi001-A-1, which demonstrates normal karyotype, morphology, pluripotency, and potential to differentiate towards three germ layers.

The adoptive transfer of chimeric antigen receptor T (CAR T) cells have been recognized as a promising therapeutic strategy for the treatment of hematological malignancies; however, clinical success using CAR T cells for the treatment of solid tumors are still limited since the T-cell function is inhibited by negative signals in the microenvironment of solid tumors. CTLA4 is a well-known immune checkpoint molecule, thus we developed a novel CAR by converting this negative signal to positive signal. The CAR developed consists of the extracellular and transmembrane domains of CTLA4 and the cytoplasmic domains of CD28 and CD3z (CTLA4-CAR T). CTLA4-CAR T cells exhibited superior cytokine secreting activities and cytotoxic to tumor cells in vitro and in xenograft models. CTLA4-CAR T cells were found to accumulate in tumors and are toxic to myeloid-derived suppressor cells (MDSCs) without signs of severe GVHD and CRS in preclinical models. Thus, this chimeric CTLA4-CAR can enhance the antitumor activity of CAR T cells and shed light on the strategy of using armed CAR T cells to target the immunomodulatory tumor microenvironment.

Pydiflumetofen is a novel and efficient broad-spectrum chiral fungicide consisting of a pair of enantiomers. A simple and sensitive chiral analytical method was established to determine the enantiomers of this chiral fungicide in food and environmental samples by ultra-high-performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) using QuEChERS method coupled with octadecylsilane-dispersive solid-phase extraction (C18-dSPE) as extraction procedure. The specific optical rotation and the absolute configuration of the enantiomers were identified by polarimetry and electronic circular dichroism (ECD). The elution order of the pydiflumetofen enantiomers on Lux Cellulose-2 was S-(−)-pydiflumetofen and R-(+)-pydiflumetofen. The average recoveries of eleven matrices ranged from 71.3% to 107.4%. The intraday relative standard deviations (RSDs) were less than 11.8%, and the interday RSDs were less than 12.6% for the two enantiomers. Stereoselective dissipation in pakchoi and soil were observed: S-(−)-pydiflumetofen was degraded faster than R-(+)-pydiflumetofen in pakchoi, causing the enantiomer fraction (EF) of the enantiomers to change from 0.50 to 0.42 in 7 days. However, R-(+)-pydiflumetofen was degraded faster than S-(−)-pydiflumetofen in soil, causing the EF of the enantiomers to change from 0.49 to 0.52 in 21 days. This study provides a method for monitoring pydiflumetofen enantiomer residues, which is crucial for improving risk assessments and the development of chiral pesticides.

Background. At present, there is a lack of drug treatment for obese patients, so it is needed to find a drug that is effective and has few side effects to treat obesity. PEX-168 is a novel long-acting glucagon-like peptide-1 receptor agonist for T2DM. It improves blood glucose with fewer side effects. The aim of the present study was to investigate the effect of PEX-168 on blood glucose and body weight of mice with simple obesity. Methods. Thirty healthy and 6-week-old C57BL/6 male mice were randomly divided into a normal control group (NC, n = 6) and obesity model group (n = 24). The obesity model mice were randomly divided into a high-fat diet group (HF) and intervention groups with different doses of PEX-168 (0.03 mg/kg, 0.1 mg/kg, and 0.3 mg/kg). Each group includes 6 mice. Body weight, food intake, and fasting blood glucose (FBG) were evaluated after intraperitoneal injection, and the intervention was performed weekly for 12 weeks. Fasting insulin (FINS) levels were measured at the 12th week. Results. Compared with HF, the food intake of mice in the intervention groups decreased transiently, but there was no difference between different doses (P>0.05). The body weight of mice in the middle and high dose of PEX-168 intervention groups decreased significantly, and the differences were statistically significant (P0.05). At the 10th week, the incidence of transient hypoglycemia was 67% and 50% in the middle- and high-dose groups, respectively. The levels of serum FINS in the intervention groups were significantly lower than those in the HF group, and the differences were statistically significant (P0.05). Conclusions. PEX-168 showed significant improvement in the FBG and FINS levels of simple obese mice. Middle and high doses of PEX-168 could reduce the weight of simple obese mice, but there was a certain risk of hypoglycemia.