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Background: A 3.0-mm ultrathin bronchoscope (UTB) with a 1.7-mm working channel provides better accessibility to peripheral bronchi. A 4.0-mm thin bronchoscope with a larger 2.0-mm working channel facilitates the use of a guide sheath (GS), ensuring repeated sampling from the same location. The 1.1-mm ultrathin cryoprobe has a smaller diameter, overcoming the limitation of the size of biopsy instruments used with UTB. In this study, we compared the endobronchial ultrasound localization rate and diagnostic yield of peripheral lung lesions by cryobiopsy using UTB and thin bronchoscopy combined with GS. Methods: We retrospectively evaluated 133 patients with peripheral pulmonary lesions with a diameter less than 30 mm who underwent bronchoscopy with either thin bronchoscope or UTB from May 2019 to May 2023. A 3.0-mm UTB combined with rEBUS was used in the UTB group, whereas a 4.0-mm thin bronchoscope combined with rEBUS and GS was used for the thin bronchoscope group. A 1.1-mm ultrathin cryoprobe was used for cryobiopsy in the two groups. Results: Among the 133 patients, peripheral pulmonary nodules in 85 subjects were visualized using r-EBUS. The ultrasound localization rate was significantly higher in the UTB group than in the thin bronchoscope group (96.0% vs. 44.6%, respectively; P < 0.001). The diagnostic yield of cryobiopsy specimens from the UTB group was significantly higher compared to the thin bronchoscope group (54.0% vs. 30.1%, respectively; p = 0.006). Univariate analysis demonstrated that the cryobiopsy diagnostic yields of the UTB group were significantly higher for lesions ≤ 20 mm, benign lesions, upper lobe lesions, lesions located lateral one-third from the hilum, and lesions without bronchus sign. Conclusions: Ultrathin bronchoscopy combined with cryobiopsy has a superior ultrasound localization rate and diagnostic yield compared to a combination of cryobiopsy and thin bronchoscopy. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed T test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using "H2O" autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance. [ABSTRACT FROM AUTHOR]

The hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of "super-enhancer omics", inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds (CMBs) can be understood as a type of target organ damage caused by hypertension. We aimed to explore the association of the CMB burden with morning blood pressure (BP) variability in patients with hypertension. We divided patients with hypertension into two groups: a group with 1–10 CMBs and a group with more than 10 CMBs. The duration, grade, medication, and control of hypertension were recorded in all patients. Morning home BP measurements were performed every 3 days for a month. A total of 791 patients were recruited. Full factor model analysis showed that higher morning home diastolic BP variability (standard deviation [SD], OR = 1.080, 95% CI: 1.024–1.140, P =.005; coefficient of variation [CV], OR = 1.076, 95% CI: 1.028–1.128, P =.002) was associated with more than 10 CMBs. Morning home systolic and diastolic blood pressure variability (SD, CV, average real variability) in more than 10 non‐lobar CMBs group was significantly higher than that in 1–10 non‐lobar CMBs group (P <.05).The multivariate analysis showed higher morning home diastolic blood pressure variability (SD, OR = 1.124, 95% CI: 1.031–1.224, P =.008; CV, OR = 1.099, 95% CI: 1.019–1.186, P =.015; average real variability, OR = 1.055, 95% CI: 0.995–1.120, P =.075) was associated with more than 10 non‐lobar CMBs. There was no significant relationship between morning home systolic blood pressure variability and more than 10 non‐lobar CMBs (P >.05). Higher morning home diastolic blood pressure variability was associated with more than 10 CMBs and more than 10 non‐lobar CMBs. [ABSTRACT FROM AUTHOR]

Sichuan taimen (Hucho bleekeri Salmonidae) populations are declining, and the status of remnant populations in the Qinling Mountains is poorly known. In this study, eDNA and creel netting were used to estimate the distributions of Sichuan taimen in two upper tributaries of the Hanjiang River. A qPCR assay was applied to detect the eDNA of H. bleekeri, and the presence of Sichuan taimen in the Taibai River, but not in the Xushui River, was confirmed. Sampling during summer achieved a relatively higher detection rate. The utility of eDNA techniques for detecting low-density Sichuan taimen was demonstrated in intricate stream ecosystems. The eDNA method can increase the efficiency of the management of endangered freshwater species, such as Sichuan taimen, by providing reliable distribution data. [ABSTRACT FROM AUTHOR]

Focal epilepsy accounts for 60% of all forms of epilepsy, but the pathogenic mechanism is not well understood. In this study, three novel mutations in NPRL3 (nitrogen permease regulator-like 3), c.937_945del, c.1514dupC and 6,706-bp genomic DNA (gDNA) deletion, were identified in three families with focal epilepsy by linkage analysis, whole exome sequencing (WES) and Sanger sequencing. NPRL3 protein is a component of the GATOR1 complex, a major inhibitor of mTOR signaling. These mutations led to truncation of the NPRL3 protein and hampered the binding between NPRL3 and DEPDC5, which is another component of the GATOR1 complex. Consequently, the mutant proteins enhanced mTOR signaling in cultured cells, possibly due to impaired inhibition of mTORC1 by GATOR1. Knockdown of nprl3 in Drosophila resulted in epilepsy-like behavior and abnormal synaptic development. Taken together, these findings expand the genotypic spectrum of NPRL3-associated focal epilepsy and provide further insight into how NPRL3 mutations lead to epilepsy. [ABSTRACT FROM AUTHOR]

Development of the hippocampus is critical for its normal maturation. However, there is no systematic study on the effects of low‐dose (≤2 Gy) neonatal X‐ray exposure on different cells at different developmental stages of the mouse hippocampus. The present study demonstrated that irradiation with 2 Gy at postnatal day (PD) 3 in mice induced anxiety and impairment of spatial learning and memory in adult mice. Neuroinflammatory cells were observed in the dentate gyrus (DG) and CA3 areas of the hippocampus at PD3 + 1. X‐ray irradiation impaired neuronal complexity and neurogenesis. However, the number of astrocytes and microglia in the hippocampus was increased the first day after irradiation, and then decreased 21 days later. The protein expression levels of NF‐κB, C/EBP homologous protein (CHOP), and γH2A histone family member X (γH2AX) increased from 7 to 21 days after irradiation, or till 90 days after irradiation for IL‐1β, whereas those of hippocampal sirtuin1 (SIRT1) decreased after 21 days of irradiation at PD3. These results suggest that neonatal X‐ray irradiation‐induced neuroinflammation impaired neuroplasticity and neurogenesis in the hippocampus, leading to the anxiety and spatial memory disorder during adulthood. The mechanisms involved in the induction of developmental neurotoxicity following low‐dose irradiation may involve the inflammation‐mediated signaling pathway IL‐1β/ SIRT1/CHOP. [ABSTRACT FROM AUTHOR]

The Chinese giant salamander (Andrias davidianus), an endangered amphibian species endemic to China, has been previously evaluated with regards to its phyletic evolution, zooecology, and ethology, but molecular mechanisms underlying its skin pigmentation remain unknown. Herein, a skin transcriptome database of different colored salamanders was established using RNA-seq, and a total of 47,911 unigenes were functionally annotated. Among these unigenes, a total of 1252 differentially expressed genes (DEGs) were annotated in the seven public databases, and six DEGs were validated by qPCR between five different skin colors and eight tissues. The results showed that TYR, TYRP1, and ASIP were significantly differentially expressed between different body colors, while TYR, TYRP1, and DCT were highly expressed in skin tissue. The full-length complementary DNA of TYR was cloned and analyzed between normal and yellow phenotypes. Three nucleotide sequence deletion sites were identified in the coding region of TYR, leading to premature termination of transcription and translation in yellow individuals. Our study provides useful data for the further study of the molecular mechanisms of melanin formation, and a valuable reference for the breeding of specific skin colors in other salamanders. [ABSTRACT FROM AUTHOR]

Triphenylmethane dyes not only can be utilized to dye silk, leather, and paper, but they also play an important part in treating parasitic, fungal, and bacterial infections of fish and fish eggs. Although these dyes are inexpensive and have a wide range of applications, they are poisonous. Therefore, their removal from wastewater is crucial for water purification. Metal–organic (MOF)/polymer porous composites were prepared by compounding highly porous MOFs with organic polymers with good stability and hydrophilicity to realize the highly efficient and stable adsorption of triphenylmethane dyes in wastewater over multiple cycles. Porous ZIF-67/PES composite microspheres for the adsorption of triphenylmethane dyes were successfully synthesized via in situ growth, and their adsorption conditions were optimized on the basis of time, pH and NaCl concentrations to investigate their adsorption performance. The as-synthesized porous ZIF-67/PES composite microspheres were characterized by using scanning electron microscopy, X-ray diffractometry, and Fourier transform infrared spectroscopy. Their adsorption kinetics and mechanisms were also studied. Their reusability and stability after cyclic adsorption processes were also investigated. The maximum adsorption capacity of the porous ZIF-67/PES composite microspheres for MG, FA and CV was 5743.28 mg g−1, 2176.52 mg g−1, and 122.78 mg g−1, respectively. Therefore, porous ZIF-67/PES composite microspheres are a potential and efficient absorbent for triarylmethane dye removal. [ABSTRACT FROM AUTHOR]

The Chinese giant salamander (Andrias davidianus) is the biggest extant and endangered amphibian, which has an incongruous sex ratio during the artificial breeding process and is sex indistinguishable in appearance. The sex development mechanism of this rare species thus needs to be explored. We therefore conducted this study to explore the molecular mechanisms of sex hallmarks or gonad maintenance genes for CGS. In this study, we sequenced and analyzed the sexually mature male and female gonads of Chinese giant salamanders (CGSs) using RNA-seq technology and found a total of 15,063 differentially expressed genes (DEGs) in the testicular and ovarian tissues, of which 7973 (52.93%) were expressed in testicular and 7090 (47.07%) in ovarian tissues. Thirteen gonad DEGs were selected based on gene expression abundance and quantified in the muscle and skin tissues of both male and female CGSs. The results showed that these 13 DEGS, out of the 20 analyzed DEGs, were expressed in both the muscle and skin tissues and only two of them (Bmp15 and ZP3) were consistent in the muscle and skin compared to the gonads of CGSs of the two sexes. Overall, our study should provide an important reference for the sex-characteristics-related genes in this type of species, shedding new light on future research on this topic. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-41 is a novel immunomodulatory cytokine involved in the pathogenesis of several inflammatory and metabolic illnesses. However, it remains unclear how IL-41 contributes to the pathogenesis of chronic obstructive pulmonary disease (COPD). Therefore, the aim of the present study was to explore the correlation between the expression level of IL-41 and acute exacerbation of COPD (AECOPD). In total, 107 patients with COPD and 56 healthy controls were recruited from the First Affiliated Hospital of Ningbo University (Ningbo, China). Serum IL-41, IL-6, and matrix metalloproteinase-2 (MMP-2) levels were evaluated using enzyme-linked immunosorbent assay. Serum amyloid A (SAA) and C-reactive protein (CRP) levels were assessed in the hospital laboratory. The levels of IL-41 were higher in the AECOPD group than in the stable COPD (SCOPD) and control groups (P<0.0001). IL-6, SAA and CRP levels, the percentage of neutrophils, as well as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were higher in the AECOPD group than those in the SCOPD and control groups. The smoking index was positively correlated with serum IL-41, CRP and SAA levels. The expression level of IL-41 was correlated with the number of acute exacerbations, severity of the exacerbations, and COPD assessment test scores in the AECOPD group. Examination of the receiver operating characteristic (ROC) curves showed that IL-41, especially when combined with other inflammatory factors, had a specific diagnostic value for AECOPD. According to the ROC curve analysis, the area under the curve (AUC) for IL-41 was 0.742 (P=0.051), and the AUC for IL-41 combined with other inflammatory factors was 0.925 (P=0.030). Increased serum IL-41 levels were associated with AECOPD and may play a role in the monitoring and evaluation of COPD. [ABSTRACT FROM AUTHOR]

Simple Summary: Schizothorax prenanti is a valuable cold-water fish that is commercially farmed in southwest China. Numerous aquaculture farmers have recently adopted high-density farming to achieve greater economic benefits, but this has rendered S. prenanti more susceptible to microbial pathogens and resulted in economic losses. Hence, the immune mechanisms of S. prenanti against pathogens should be investigated. Heat shock proteins (Hsps) comprise a family of molecular chaperones that are involved in immune pathways. Here, we identified and cloned the cDNA encoding SpHsp27 gene and detected its tissue distribution and using polyinosinic-polycytidylic acid [Poly (I:C)] as a viral analog to challenge the fish. We also explored the expression of SpHsp27, SpHsp60, SpHsp70, and SpHsp90 in four immune organs from fish that were injected with Poly (I:C). We found that Poly (I:C) induced SpHsp27 expression in all of these tissues, and significantly up-regulated most SpHsps genes compared with controls that were injected with phosphate-buffered saline. However, temporal expression and tissues were organ-specific. The present findings will help to further clarify the roles of Hsp genes in the mechanisms of antiviral immunity in fish. We identified and cloned cDNA encoding the heat shock protein (Hsp) 27 gene from Schizothorax prenanti (SpHsp27), and compared its expression with that of SpHsp60, SpHsp70, and SpHsp90 in the liver, head kidney, hindgut, and spleen of S. prenanti that were injected with polyinosinic-polycytidylic acid [Poly (I:C)]. The SpHsp27 partial cDNA (sequence length, 653 bp; estimated molecular mass, 5.31 kDa; theoretical isoelectric point, 5.09) contained an open reading frame of 636 bp and a gene encoding 211 amino acids. The SpHsp27 amino acid sequence shared 61.0–92.89% identity with Hsp27 sequences from other vertebrates and SpHsp27 was expressed in seven S. prenanti tissues. Poly (I:C) significantly upregulated most SpHsps genes in the tissues at 12 or 24 h (p < 0.05) compared with control fish that were injected with phosphate-buffered saline. However, the intensity of responses of the four SpHsps was organ-specifically increased. The expression of SpHsp27 was increased 163-fold in the head kidney and 26.6-fold SpHsp27 in the liver at 24 h after Poly (I:C) injection. In contrast, SpHsp60 was increased 0.97–1.46-fold in four tissues and SpHsp90 was increased 1.21- and 1.16-fold in the liver and spleen at 12 h after Poly (I:C) injection. Our findings indicated that Poly (I:C) induced SpHsp27, SpHsp60, SpHsp70, and SpHsp90 expression and these organ-specific SpHsps are potentially involved in S. prenanti antiviral immunity or mediate pathological process. [ABSTRACT FROM AUTHOR]

Simple Summary: The Taibai stream salamander (Batrachuperus taibaiensis) is a protected species endemic to the Zhouzhi Heihe River. Few traditional studies have been conducted on the distribution of B. taibaiensis, leading to irregular discoveries. Environmental DNA (eDNA) is an ideal species detection technique that can increase accuracy and decrease the cost of population surveys. Here, we have established an optimal method for obtaining the eDNA of B. taibaiensis from water samples, which provides a theoretical basis and reference for resource investigation and protection of B. taibaiensis. Moreover, this study highlights the detection of a rare species in a river for use in further research. The Taibai stream salamander (Batrachuperus taibaiensis) is a recently described species of the genus Batrachuperus that occurs in the Zhouzhi Heihe River and is endangered in its native range. Here, we have established a method for water environmental DNA (eDNA) analysis of Batrachuperus using a series of optimizations. We have designed a specific set of primers for the genus Batrachuperus to amplify a 160 bp fragment of Cytb. The sequences were obtained from nested PCR on eDNA extracted from water samples, after which DNA barcoding was performed according to sequence analysis to determine the presence of the target species in the water. The method was validated using water from the Zhouzhi Heihe River with known B. taibaiensis populations and found that B. taibaiensis eDNA can move at least 150 m downstream from its point of origin. This study is the first to establish an optimal method for obtaining the eDNA of Batrachuperus from water samples, which provides a theoretical basis for resource investigation and the protection of B. taibaiensis in future research. It is also an example of the eDNA extraction of other species that live in similar waters and are less genetically diverse between species. [ABSTRACT FROM AUTHOR]

The addition of supplemental light (SL) is an effective way to offset insufficient lighting. Although it is commonly believed that SL increases leaf photosynthesis and therefore improves yield and fruit flavor, the mechanism underlying the effects of SL on the photosystem II (PSII) apparatus remains unclear, and SL leads to high energy consumption. In order to save energy, we investigated the physiological status of the PSII apparatus, plant growth parameters and fruit parameters under two types of overhead SL with a low daily energy consumption of 0.0918 kWh m-2. The results showed that SL significantly increased the leaf chlorophyll content from full unfolding to yellowing. However, a remarkable increase in the absorption flux per cross-section (ABS/CS), the quantum yield of electron transport (φEo) and the performance index (PIabs) was observed only in a relatively short period of the leaf life cycle. SL also enhanced the fruit yield and quality. The obviously increased ΔVK and ΔVJ components of the chlorophyll fluorescence induction kinetic (OJIP) curve, along with the significantly decreased PIabs from days 40–60 after unfolding in the SL-treated groups, resulted in more rapid leaf aging and earlier fruit ripening compared with the control plants (CK). Therefore, an energy-friendly SL strategy can alter the physiological status of the PSII apparatus, affecting yield and fruit quality and maturity. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic transformation is one of the most serious complications in intravenous thrombolysis. Studies show that the existence of more than 10 cerebral microbleeds is strongly associated with hemorrhagic transformation. The current study attempts to develop and validate a clinical prediction model of more than 10 cerebral microbleeds. Methods: We reviewed the computed tomography markers of cerebral small vessel diseases and the basic clinical information of acute ischemic stroke patients who were investigated using susceptibility weighted imaging from 2018 to 2021. A clinical prediction model of more than 10 cerebral microbleeds was established. Discrimination, calibration, and the net benefit of the model were assessed. Finally, a validation was conducted to evaluate the accuracy and stability of the model. Results: The multivariate logistic regression model showed hypertension, and some computed tomography markers (leukoaraiosis, lacunar infarctions, brain atrophy) were independent risk factors of more than 10 cerebral microbleeds. These risk factors were used for establishing the clinical prediction model. The area under the receiver operating characteristic curve (AUC) was 0.894 (95% CI: 0.870–0.919); Hosmer–Lemeshow chi-squared test yielded χ2 = 3.946 (P = 0.862). The clinical decision cure of the model was higher than the two extreme lines. The simplified score of the model ranged from 0 to 12. The model in the internal and external validation cohort also had good discrimination (AUC 0.902, 95% CI: 0.868–0.937; AUC 0.914, 95% CI: 0.882–0.945) and calibration (P = 0.157, 0.247), and patients gained a net benefit from the model. Conclusions: We developed and validated a simple scoring tool for acute ischemic stroke patients with more than 10 cerebral microbleeds; this tool may be beneficial for paradigm decision regarding intravenous recombinant tissue plasminogen activator therapy of acute ischemic stroke. [ABSTRACT FROM AUTHOR]

In the present study, genome-wide CNVs were detected in a total of 301 samples from 10 Chinese indigenous horse breeds using the Illumina Equine SNP70 Bead Array, and the candidate genes related to adaptability to high temperature and humidity in Jinjiang horses were identified and validated. We determined a total of 577 CNVs ranging in size from 1.06 Kb to 2023.07 Kb on the 31 pairs of autosomes. By aggregating the overlapping CNVs for each breed, a total of 495 CNVRs were detected in the 10 Chinese horse breeds. As many as 211 breed-specific CNVRs were determined, of which 64 were found in the Jinjiang horse population. By removing repetitive CNV regions between breeds, a total of 239 CNVRs were identified in the Chinese indigenous horse breeds including 102 losses, 133 gains and 4 of both events (losses and gains in the same region), in which 131 CNVRs were novel and only detected in the present study compared with previous studies. The total detected CNVR length was 41.74 Mb, accounting for 1.83% of the total length of equine autosomal chromosomes. The coverage of CNVRs on each chromosome varied from 0.47% to 15.68%, with the highest coverage on ECA 12, but the highest number of CNVRs was detected on ECA1 and ECA24. A total of 229 genes overlapping with CNVRs were detected in the Jinjiang horse population, which is an indigenous horse breed unique to the southeastern coast of China exhibiting adaptability to high temperature and humidity. The functional annotation of these genes showed significant relation to cellular heat acclimation and immunity. The expression levels of the candidate genes were validated by heat shock treatment of various durations on fibroblasts of horses. The results show that the expression levels of HSPA1A were significantly increased among the different heat shock durations. The expression level of NFKBIA and SOCS4 declined from the beginning of heat shock to 2 h after heat shock and then showed a gradual increase until it reached the highest value at 6 h and 10 h of heat shock, respectively. Breed-specific CNVRs of Chinese indigenous horse breeds were revealed in the present study, and the results facilitate mapping CNVs on the whole genome and also provide valuable insights into the molecular mechanisms of adaptation to high temperature and humidity in the Jinjiang horse. [ABSTRACT FROM AUTHOR]

Meige syndrome (MS) is cranial dystonia characterized by the combination of upper and lower cranial involvement and including binocular eyelid spasms (blepharospasm; BSP) and involuntary movements of the jaw muscles (oromandibular dystonia; OMD). The etiology and pathogenesis of this disorder of the extrapyramidal system are not well-understood. Neurologic and ophthalmic examinations often reveal no abnormalities, making diagnosis difficult and often resulting in misdiagnosis. A small proportion of patients have a family history of the disease, but to date no causative genes have been identified to date and no cure is available, although botulinum toxin A therapy effectively mitigates the symptoms and deep brain stimulation is gaining increasing attention as a viable alternative treatment option. Here we review the history and progress of research on MS, BSP, and OMD, as well as the etiology, pathology, diagnosis, and treatment. [ABSTRACT FROM AUTHOR]

Tobacco smoking is the main risk factor for many diseases such as chronic obstructive pulmonary disease as well as lung cancer and cigarettes. Smokers usually keep continuing to smoke during their mental activities in the evening between dinner and sleep time on work days. So it is critical to elucidate the relationship between cigarettes daily consumption and mental activities after dinner. A survey designed by ourselves was finished among 369 patients who came to our clinic for smoking cessation. Age, gender, BMI, cigarettes consumption were recorded and analyzed. Statistically, Pearson correlation test and general linear model test were used. Compared to ≤ 40 years' group, patients with mental activities after dinner consumed more cigarettes than those without mental activities (22.80 ± 10.86 vs. 30.88 ± 18.69, P value < 0.001). The Pearson correlation test showed no interact effects on age and BMI, and general linear model test showed that the cigarettes numbers between smokers with mental activities after dinner and smokers without mental activities after dinner are different (P value < 0.001). Mental activities from dinner finish to sleep time increase cigarettes consumption. It provides evidence that mental thinking activities after dinner is a risk factor of tobacco using. [ABSTRACT FROM AUTHOR]

Extremely low nucleotide diversity of modern horse Y-chromosome has been reported, and only poor phylogenetic resolution could be resulted from limited Y-chromosome markers. In this study, three types of horse Y-chromosome markers, including Single-nucleotide polymorphisms (SNPs), copy number variants (CNVs), and allele-specific CNVs, were developed by screening more than 300 male horses from 23 indigenous Chinese horse populations and 4 imported horse breeds. Fourteen segregating sites including a novel SNP in the AMELY gene were found in approximately 53 kb of male-specific Y-chromosome sequences. CNVs were detected at 11 of 14 sites, while allele-specific CNVs at 6 polymorphic sites in repeated fragments were also determined. The phylogenetic analyses with the SNPs identified in this study and previously published 51 SNPs obtained mainly from European horses showed that indigenous Chinese horses exhibit much deeper divergence than European and Middle Eastern horses, while individuals of Chinese horses with the C allele of the AMELY gene constituted the most ancient group. Via SNPs, CNVs, and allele-specific CNVs, much higher diversity of paternal lines can be detected than those identified with merely SNPs. Our results indicated that there are ancient paternal horse lines preserved in southwestern China, which sheds new light on the domestication and immigration of horses, and suggest that the priorities of the conservation should be given to the ancient and rare paternal lines. These three marker types provided finer phylogenetic resolution of horse patrilineal lines, and the strategies used in the present study also provide valuable reference for the genetic studies of other mammalian patrilineages. [ABSTRACT FROM AUTHOR]

Purpose: Super-enhancer (SE)-associated oncogenes extensively potentiate the uncontrolled proliferation capacity of cancer cells. In this study, we aimed to identify the SE-associated hub genes associated with the clinical characteristics of chronic myeloid leukemia (CML). Methods: Eigengenes from CML clinical modules were determined using weighted gene co-expression network analysis (WGCNA). Overlapping genes between eigengenes and SE-associated genes were used to construct protein–protein interaction (PPI) networks and annotate for pathway enrichment analysis. Expression patterns of the top-ranked SE-associated hub genes were further determined in CML patients and healthy controls via real-time PCR. After treatment of K562 cells with the BRD4 inhibitor, JQ1, for 24 hrs, mRNA and protein levels of SE-associated hub genes were evaluated using real-time PCR and Western blotting, respectively. H3K27ac, H3K4me1 and BRD4 ChIP-seq signal peaks were used to predict and identify SEs visualized by the Integrative Genomics Viewer. Results: The yellow module was significantly related to the status and pathological phase of CML. SE-associated hub candidate genes were mainly enriched in the cell cycle pathway. Based on the PPI networks of hub genes and the top rank of degree, five SE-associated genes were identified: specifically, BUB1, CENPO, KIF2C, ORC1, and RRM2. Elevated expression of these five genes was not only related to CML status and phase but also positively regulated by SE and suppressed by the BRD4 inhibitor, JQ1, in K562 cells. Strong signal peaks of H3K27ac, H3K4me1 and BRD4 ChIP-seq of the five genes were additionally observed close to the predicted SE regions. Conclusion: This is the first study to characterize SE-associated genes linked to clinical characteristics of CML via weighted gene co-expression network analysis. Our results support a novel mechanism involving aberrant expression of hub SE-associated genes in CML patients and K562 cells, and these genes will be potential new therapeutic targets for human leukemia. [ABSTRACT FROM AUTHOR]

Summary: Objective: To identify the causative gene of autosomal dominant paroxysmal kinesigenic dyskinesia and benign familial infantile seizures (PKD/BFIS) in a large Chinese family and explore the potential pathogenic mechanism of a PRRT2 (proline‐rich transmembrane protein 2) variant. Methods: Genetic testing was performed via whole exome sequencing. Western blotting and immunofluorescence were used to analyze the protein expression level and subcellular localization of the PRRT2 mutant in HeLa cells and N2A cells. Coimmunoprecipitation was conducted to investigate the interaction of the PRRT2 mutant with syntaxin 1B (STX1B). Results: In a large Chinese family with autosomal dominant PKD/BFIS showing wide phenotypic heterogeneity, including patients suffering from PKD, BFIS, or epilepsy and asymptomatic variant carriers, a c.621dupA variant in PRRT2 was identified in the proband and was shown to cosegregate with the phenotype in this family. This variant results in premature termination at codon 224, producing a truncated protein (p.Ser208Ilefs*17) in which the two conserved hydrophobic segments and the cytoplasmic loop are missing. Both the expression and subcellular localization of PRRT2 are strongly affected by the c.621dupA variant. In addition, we found that PRRT2 directly interacts with STX1B, a SNARE protein critical for neurotransmitter release, whereas the truncated variant p.Ser208Ilefs*17 lacking the helix‐loop‐helix domain fails to bind to STX1B. Significance: Our findings identified a PRRT2 variant in a family with PKD/BFIS and confirmed STX1B as a new binding partner of PRRT2, which suggested that the loss of the interaction between PRRT2 and STX1B may contribute to the pathogenesis of PKD/BFIS. [ABSTRACT FROM AUTHOR]

Non‑small cell lung carcinoma (NSCLC) is a major subtype of lung cancer. Aberrant DNA methylation has been frequently observed in NSCLC. The aim of the present study was to investigate the role of MyoD family inhibitor (MDFI) methylation in NSCLC. Formalin‑fixed paraffin‑embedded tumor tissues and adjacent non‑cancerous tissues were collected from a total of 111 patients with NSCLC. A methylation assay was performed using the quantitative methylation‑specific polymerase chain reaction method. The percentage of methylated reference was used to represent the methylation level of the MDFI promoter. Data mining of a dataset from The Cancer Genome Atlas (TCGA) demonstrated that MDFI promoter methylation levels were significantly increased in 830 tumor tissues compared with 75 non‑tumor tissues (P=0.012). However, the results on tissues obtained in the present study indicated that the MDFI promoter methylation levels in tumor tissues were not significantly different compared with those in the adjacent non‑tumor tissues (P=0.159). Subsequent breakdown analysis identified that higher MDFI promoter methylation levels were significantly associated with NSCLC in females (P=0.031), but not in males (P=0.832). Age‑based subgroup analysis demonstrated that higher MDFI promoter methylation levels were significantly associated with NSCLC in younger patients (≤65 years; P=0.003), but not in older patients (P=0.327). In addition, the association of MDFI methylation with NSCLC was significant in non‑smokers (P=0.014), but not in smokers (P=0.832). Similar results also have been determined from subgroup analysis of the TCGA datasets. The Gene Expression Omnibus database indicated MDFI expression restoration in partial lung cancer cell lines (H1299 and Hotz) following demethylation treatment. However, it was identified that MDFI promoter hypermethylation was not significantly associated with prognosis of NSCLC (P>0.05). In conclusion, the present study indicated that the association of higher methylation of the MDFI promoter with NSCLC may be specific to females, non‑smokers and people aged ≤65. [ABSTRACT FROM AUTHOR]

Familial idiopathic basal ganglia calcification (IBGC) is a genetic condition with a wide spectrum of neuropsychiatric symptoms, including parkinsonism and dementia. Here, we identified mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), in IBGC-affected families of varied ancestry, and we observed significantly impaired phosphate transport activity for all assayed PiT2 mutants in Xenopus laevis oocytes. Our results implicate altered phosphate homeostasis in the etiology of IBGC. [ABSTRACT FROM AUTHOR]

The Jinjiang horse is a unique Chinese indigenous horse breed distributed in the southern coastal areas, but the ancestry of Jinjiang horses is not well understood. Here, we used Equine SNP70 Bead Array technology to genotype 301 horses representing 10 Chinese indigenous horse breeds, and we integrated the published genotyped data of 352 individuals from 14 foreign horse breeds to study the relationships between Jinjiang horses and horse breeds from around the world. Principal component analysis (PCA), linkage disequilibrium (LD), runs of homozygosity (ROH) analysis, and ancestry estimating methods were conducted to study the population relationships and the ancestral sources and genetic structure of Jinjiang horses. The results showed that there is no close relationship between foreign horse breeds and Jinjiang horses, and Jinjiang horses shared a similar genetic background with Baise horses. TreeMix analysis revealed that there was gene flow from Chakouyi horses to Jinjiang horses. The ancestry analysis showed that Baise horses and Chakouyi horses are the most closely related ancestors of Jinjiang horses. In conclusion, our results showed that Jinjiang horses have a native origin and that Baise horses and Chakouyi horses were key ancestral sources of Jinjiang horses. The study also suggested that ancient trade activities and the migration of human beings had important effects on indigenous horse breeds in China. [ABSTRACT FROM AUTHOR]

Aberrant DNA methylation can be a potential genetic mechanism in non-small cell lung cancer (NSCLC). However, inconsistent findings existed among the recent association studies between cigarette smoking and gene methylation in lung cancer. The purpose of our meta-analysis was to evaluate the role of gene methylation in the smoking behavior of NSCLC patients. A total of 116 genes were obtained from 97 eligible publications in the current meta-analyses. Our results showed that 7 hypermethylated genes (including CDKN2A, RASSF1, MGMT, RARB, DAPK, WIF1 and FHIT) were significantly associated with the smoking behavior in NSCLC patients. The further population-based subgroup meta-analyses showed that the CDKN2A hypermethylation was significantly associated with cigarette smoking in Japanese, Chinese and Americans. In contrast, a significant association of RARB hypermethylation and smoking behavior was only detected in Chinese but not in Japanese. The genes with altered DNA methylation were likely to be potentially useful biomarkers in the early diagnosis of NSCLC. [ABSTRACT FROM AUTHOR]

Genetic susceptibility to obstructive sleep apnea (OSA) has been a research focus in the scientific community in the past few years. In this study, we recruited 375 subjects to investigate whether functional polymorphisms in the promoter region of matrix metalloproteinase (MMP)-2 (-1306C/T) and MMP-9 (-1562C/T) increased susceptibility to OSA. Our study showed no significant association between MMP-2 -1306C/T polymorphism and risk of OSA (T vs. C: OR = 1.01, 95% CI = 0.67-1.52; P = 0.97). Compared with the MMP-9 -1562C allele, the -1562T allele was associated with increased risk of OSA (T vs. C: OR = 1.56, 95% CI = 1.02-2.39; P = 0.04). However, neither MMP-2 -1306C/T nor MMP-9 -1562C/T polymorphism was found to be associated with severity of the disease. Our study suggested that the MMP-2 -1306C/T polymorphism was not associated with OSA susceptibility, whereas the MMP-9 -1562T allele was associated with increased risk of OSA. [ABSTRACT FROM AUTHOR]