Taking a color photo: A homozygous 25-bp deletion in Bace2 may cause brown-and-white coat color in giant pandas.

Brown-and-white giant pandas (hereafter brown pandas) are distinct coat color mutants found exclusively in the Qinling Mountains, Shaanxi, China. However, its genetic mechanism has remained unclear since their discovery in 1985. Here, we identified the genetic basis for this coat color variation using a combination of field ecological data, population genomic data, and a CRISPR-Cas9 knockout mouse model. We de novo assembled a long-read-based giant panda genome and resequenced the genomes of 35 giant pandas, including two brown pandas and two family trios associated with a brown panda. We identified a homozygous 25-bp deletion in the first exon of Bace2, a gene encoding amyloid precursor protein cleaving enzyme, as the most likely genetic basis for brown-and-white coat color. This deletion was further validated using PCR and Sanger sequencing of another 192 black giant pandas and CRISPR-Cas9 edited knockout mice. Our investigation revealed that this mutation reduced the number and size of melanosomes of the hairs in knockout mice and possibly in the brown panda, further leading to the hypopigmentation. These findings provide unique insights into the genetic basis of coat color variation in wild animals.

Impact of Recombinant Human Granulocyte Colony-Stimulating Factor Combined with Aspirin on Clinical Pregnancy Outcomes and Endometrial Receptivity in Patients with Recurrent Abortion: A Retrospective Study.

Objective: This study investigates the impact of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and aspirin on endometrial receptivity and clinical pregnancy outcomes in individuals with a history of recurrent abortions. Methods: In this retrospective study, 131 individuals with recurrent abortions treated at our facility from July 2019 to December 2020 were split into two groups: mixed therapy and control. The mixed therapy group received aspirin and rhG-CSF, while the control group had no specific treatment. Primary endpoint: live birth rate; secondary: pregnancy rate at 20 weeks. We also evaluated abortion rates, newborn weight, pre-eclampsia, premature delivery, fetal/newborn congenital malformations, and maternal drug adverse reactions. Additionally, we analyzed endometrial blood flow three weeks post-treatment. Results: The analysis encompassed 131 individuals, with 65 in the control group and 66 in the mixed therapy group. Notably, the mixed therapy group (n = 54) exhibited a markedly higher live birth rate than the control group (P < .05). In terms of medication-related side effects, the control group showed no adverse reactions, while the mixed therapy group reported mild effects (skin itching in three cases, leukocytosis in seven, and bone pain in one case) that did not significantly impact outcomes. Pre-treatment, the mixed therapy group had a notably lower resistive index, pulsatility index, and systolic-to-diastolic ratio compared to the control group, with statistical significance (P < .05). The control group's indices remained unchanged (P > .05). Conclusions: In women with a history of recurrent abortions, the administration of recombinant human granulocyte colony-stimulating factor and aspirin can effectively and safely improve live birth rates. This improvement may be associated with enhanced endometrial receptivity.

The clinical, myopathological, and molecular characteristics of 26 Chinese patients with dysferlinopathy: a high proportion of misdiagnosis and novel variants.

BACKGROUND: Dysferlinopathy is an autosomal recessive muscular dystrophy caused by pathogenic variants in the dysferlin (DYSF) gene. This disease shows heterogeneous clinical phenotypes and genetic characteristics. METHODS: We reviewed the clinical and pathological data as well as the molecular characteristics of 26 Chinese patients with dysferlinopathy screened by immunohistochemistry staining and pathogenic variants in DYSF genes. RESULTS: Among 26 patients with dysferlinopathy, 18 patients (69.2%) presented as Limb-girdle Muscular Dystrophy Type R2 (LGMD R2), 4 (15.4%) had a phenotype of Miyoshi myopathy (MM), and 4 (15.4%) presented as asymptomatic hyperCKemia. Fifteen patients (57.7%) were originally misdiagnosed as inflammatory myopathy or other diseases. Fifteen novel variants were identified among the 40 variant sites identified in this cohort. CONCLUSION: Dysferlinopathy is a clinically and genetically heterogeneous group of disorders with various phenotypes, a high proportion of novel variants, and a high rate of misdiagnosis before immunohistochemistry staining and genetic analysis.

Psychometric Properties and Factor Analysis of a Short Form of the Multidimensional Measure of Emotional Abuse.

The 28-item Multidimensional Measure of Emotional Abuse (MMEA) assesses four common forms of emotional abuse in intimate relationships and has been used extensively to study the development of intimate partner violence (IPV), the consequences of emotional abuse, and the outcomes of IPV interventions. The current study provides psychometric analyses of a shortened version of the MMEA using self-report data from a sample of men receiving treatment at a community-based relationship violence intervention program (RVIP; N = 467) and reports from their relationship partners (N = 252), and data from a sample of undergraduate students (N = 194) who reported on their own and their partners' abusive behavior. Theoretical and statistical considerations, including internal consistency after item deletion, were used to select items for the shortened version. In the clinic sample (for self- and partner reports) and in the undergraduate sample (for self-report only), the 16-item MMEA-Short Form (MMEA-SF) retains the 4-factor structure of the 28-item MMEA. In both samples and across reporting methods (self and partner), the 16-item MMEA-SF has good internal consistency, good concurrent validity with the Revised Conflict Tactics Scales (CTS2) psychological aggression subscale, and similar correlations with CTS2 physical assault subscale as the original 28-item MMEA version. The MMEA-SF can reduce assessment burden while maintaining good domain coverage and strong psychometric properties and will be an asset to researchers and practitioners who need a brief, multifaceted measure of emotional relationship abuse in both clinic and undergraduate samples.

[A clinical research report on the pathophysiological characteristics of exercise in patients with mitral regurgitation].

Objective: Cardiopulmonary exercise testing (CPET) was used to investigate the exercise pathophysiology of mitral regurgitation. Methods: 26 patients with moderate and severe mitral regurgitation who completed standardized extreme exercise CPET under strict quality control after signing informed consent since 2016, and 11 normal subjects in the same period as the control group. The core indexes of CPET were analyzed and calculated according to the standard method and compared with normal subjects for intergroup statistical independent sample t-test. At the same time, the patients with heart failure and exercise oscillation breathing (OB) were divided into two subgroups: 11 cases without heart failure, 15 cases with heart failure, 8 cases with non-OB and 18 cases with OB, and their similarities and differences were compared between each subgroup. Results: The core indexes of CPET, such as peak oxygen uptake (85.60 ±9.06)%pred and anaerobic threshold (AT, (87.59 ±15.38)%pred) were normal. The peak oxygen uptake of CPET in patients with mitral regurgitation was (48.15 ±12.11)%pred, peak oxygen pulse was (66.57 ±12.20)%pred, AT was (56.75 ±11.50)%pred, oxygen uptake efficiency plateau was (88.24 ±16.42)%pred , lowest value of carbon dioxide ventilatory efficiency was (125.89 ±27.05)%pred and slope of carbon dioxide ventilatory efficiency was (128.31 ±31.68)%pred. Among them, only oxygen uptake efficiency plateau (OUEP) was normal and low, and the other indexes were significantly abnormal. There were significant differences between the patients and the control group (P<0.01). There was no significant difference between the non-OB group and the OB group, but there was significant difference between the non-OB group and the control group (P<0.05). There was no significant difference between the non-heart failure group and the heart failure group, but there was significant difference between the non-heart failure group and the control group. Conclusion: All the core indexes of cardiopulmonary exercise are significantly abnormal in patients with mitral regurgitation who are significantly lower than those in normal subjects except for the low effectiveness of oxygen ventilation. And with or without heart failure and OB did not affect the cardiopulmonary function.

Evaluation of STEM Engagement Activities on the Attitudes and Perceptions of Mechanical Engineering S-STEM Scholars.

Since 2009, the mechanical engineering (ME) scholarship-science technology engineering and mathematics (S-STEM) Program at the University of Maryland Baltimore County (UMBC) has provided financial support and program activities to ME undergraduate students aiming at improving their retention and graduation rates. The objective of this study is to identify program activities that were most effective to help students for improvements. Current ME S-STEM scholars were asked to complete a survey that measures their scientific efficacy, engineering identity, expectations, integration, and sense of belonging, as well as how program activities impact their attitudes and perceptions. Analyses of 36 collected surveys showed that scholars reported high levels of engineering identity, expectations, and sense of belonging. However, further improvements were needed to help students in achieving scientific efficacy and academic integration into the program. Results demonstrated that pro-active mentoring was the most effective method contributing to positive attitudes and perceptions. The implemented S-STEM research-related activities and internship were viewed favorably by the scholars in helping them establish their scientific efficacy and engineering identity, and understand their expectations and goals. Community building activities were considered helpful for them to integrate into campus life and improve their sense of belonging to the campus and program. Scholars identified mentoring, research related activities, internships, and social interaction with faculty and their peers as important factors for their retention and graduation. Although the sample size was small in the study, we believe that the cost-effective activities identified could be adopted by other institutions to further improve students' retention and graduation rates in engineering programs.

The Contributions of Language Skills and Comprehension Monitoring to Chinese Reading Comprehension: A Longitudinal Investigation.

This study examined how vocabulary, syntactic knowledge, and orthographic knowledge are related to comprehension monitoring and whether comprehension monitoring mediates the relations between these language skills and reading comprehension. Eighty-nine Chinese children were assessed on their vocabulary, syntactic knowledge, orthographic knowledge, and comprehension monitoring in Grade 1. Their reading comprehension skills were assessed in Grade 1 and Grade 3. Results showed that in Grade 1, comprehension monitoring mediated the relations between vocabulary and syntactic knowledge and reading comprehension. For Grade 3 reading comprehension, syntactic knowledge in Grade 1 was the only significant predictor. These findings indicate that multiple language skills make direct and indirect contributions via comprehension monitoring to Chinese reading comprehension, and the relations would change as children's reading skills develop.

Effect of AAV9-hIGF-1 on inflammatory reaction in mdx mice and its mechanism.

This study aimed to the role of insulin-like growth factor 1 (IGF-1) in Duchenne muscular dystrophy (DMD), the inflammatory response and the potential mechanism of the effect hIGF1 exerted in muscle inflammation were also been explored. In this study, AAV9, a carrier of the human IGF-1 gene, was injected into mdx mice to observe the role of IGF-1 in DMD. Routine histopathological staining, immunofluorescence and western blot were used to detect the inflammatory response. In addition, we also explored the potential mechanism of the role of hIGF1 in muscle inflammation. The expression of AAV9 in myocardium and muscle tissue of AAV9-GFP group was detected by GFP method. GFP was expressed in different tissues of mdx mice, especially in anterior tibial muscle, triceps muscle and other tissues. The percentage of anterior tibial muscle inflammation area in CD68 and AAV9-hIGF-1 group was lower than that in AAV-GFP group, and the percentage of anterior tibial muscle inflammation area in AAV9-hIGF-1 group (1.78 ± 0.47%) was significantly lower than that in AAV GFP group (3.4 ± 1.22%) (P < 0.05). Western-blot showed that AAV-hIGF-1 group (0.45 + 0.07%) was lower than that of AAV-GFP group (0.76 + 0.13%), higher than the normal group (0.38 + 0.06%). The difference was statistically significant (P < 0.05). In conclusion, this study confirmed that hIGF-1 can reduce the inflammatory response and macrophage infiltration in mdx mice, and further proved that hIGF-1 can down regulate the expression of NF-κB signal pathway, which has anti-inflammatory effect.

TAS2R20 variants confer dietary adaptation to high-quercitrin bamboo leaves in Qinling giant pandas.

Sensitivity to bitter tastes provides animals with an important means of interacting with their environment and thus, influences their dietary preferences. Genetic variants encoding functionally distinct receptor types contribute to variation in bitter taste sensitivity. Our previous study showed that two nonsynonymous sites, A52V and Q296H, in the TAS2R20 gene are directionally selected in giant pandas from the Qinling Mountains, which are speculated to be the causative base-pair changes of Qinling pandas for the higher preference for bamboo leaves in comparison with other pandas. Here, we used functional expression in engineered cells to identify agonists of pTAS2R20 (i.e., giant panda's TAS2R20) and interrogated the differences in perception in the in vitro responses of pTAS2R20 variants to the agonists. Our results show that pTAS2R20 is specifically activated by quercitrin and that pTAS2R20 variants exhibit differences in the sensitivity of their response to the agonist. Compared with pTAS2R20 in pandas from other areas, the receptor variant with A52V and Q296H, which is most commonly found in Qinling pandas, confers a significantly decreased sensitivity to quercitrin. We subsequently quantified the quercitrin content of the leaves of bamboo distributed in the Qinling Mountains, which was found to be significantly higher than that of the leaves of bamboo from panda habitats in other areas. Our results suggest that the decreased sensitivity to quercitrin in Qinling pandas results in higher-quercitrin-containing bamboo leaves to be tasting less bitter to them and thus, influences their dietary preference. This study illustrates the genetic adaptation of Qinling pandas to their environments and provides a fine example of the functional effects of directional selection in the giant panda.

A primer for using multilevel models to meta-analyze single case design data with AB phases.

Meta-analytic methods provide a way to synthesize data across treatment evaluation studies. However, these well-accepted methods are infrequent with behavior analytic studies. Multilevel models may be a promising method to meta-analyze single-case data. This technical article provides a primer for how to conduct a multilevel model with single-case designs with AB phases using data from the differential-reinforcement-of-low-rate behavior literature. We provide details, recommendations, and considerations for searching for appropriate studies, organizing the data, and conducting the analyses. All data sets are available to allow the reader to follow along with this primer. The purpose of this technical article is to minimally equip behavior analysts to complete a meta-analysis that will summarize a current state of affairs as it relates to the science of behavior analysis and its practice. Moreover, we aim to demonstrate the value of analyses of this sort for behavior analysis.

Adaptation and assessment of the Child Feeding Questionnaire for Chinese immigrant families of young children in the United States.

BACKGROUND: Chinese immigrant mothers have been found to hold cultural-specific beliefs about children's weight and use cultural-specific feeding practices when feeding their children. However, current measurements of child feeding, including the widely used Child Feeding Questionnaire (CFQ), do not capture these cultural-specific beliefs and practices. Thus, the present study examined the underlying factor structure of the original CFQ (7-factor model) and the modified CFQ with additional Asian cultural-specific feeding items (8- and 9-factor model) and assessed the validity of the CFQ among U.S. Chinese immigrant mothers. METHOD: First-generation Chinese immigrant mothers (N = 216, Mage = 38.31, SDage = 4.34) with young children (Mage = 5.14, SDage = 1.49; 47.70% females) completed the CFQ (Birch et al., 2001), with two additional items capturing Asian cultural-specific feeding beliefs and practices. Children's and parents' body mass index and mothers' perceptions of their children's body size were also assessed. RESULTS: Our findings revealed that the 9-factor model, which included the cultural-specific feeding items, was the most optimal model to represent the factor structure of feeding beliefs and practices among U.S. Chinese immigrant mothers of young children. Mothers' feeding beliefs and practices were associated with children's and mothers' body mass index and mothers' perceptions of their children's body size. CONCLUSIONS: The present study highlighted the importance of cultural-specific beliefs and practices when examining parents' feeding perceptions, beliefs, and practices.

Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling.

We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.

Identification of a novel SGCA missense mutation in a case of limb-girdle muscular dystrophy 2D with the absence of four sarcoglycan proteins.

Limb-girdle muscular dystrophy 2D (LGMD2D) is caused by mutations in the α-sarcoglycan gene (SGCA). Due to lack of specificity, it is impossible to identify LGMD2D only by clinical symptoms and conventional immunohistochemical staining. The loss of any protein (α-, ß-, γ-, δ-sarcoglycan) that represent sarcoglycanopathy may cause reduction or absence of the other three proteins. Here, we report a patient with a complete loss of all the four proteins. Next generation sequencing (NGS) results showed a missense mutation (C.218 C > T) and a partial heterozygous deletion containing exons 7 and 8 of SGCA, which led to the final diagnosis of the patient. The discovery of this new mutation could broaden the spectrum of SGCA mutations, which may be associated with putative LGMD2D, especially when all the four proteins are completely missing.

High preoperative plasma fibrinogen and serum albumin score is associated with poor survival in operable esophageal squamous cell carcinoma.

This study was performed to investigate the prognostic significance of a cumulative score based on the preoperative plasma fibrinogen and serum albumin (FA score) in operable esophageal squamous cell carcinoma (ESCC). Clinicopathologic characteristics, preoperative fibrinogen, and albumin concentrations were retrospectively reviewed in patients who underwent transthoracic esophagectomy. The optimal cutoff value was defined as 4.0 g/L for fibrinogen according to previous studies and as 41.0 g/L for albumin for the lower quartile. Subjects with elevated fibrinogen and decreased albumin levels were allocated a score of 2, those with only one of these two abnormalities were assigned a score of 1, and those with neither of the abnormalities were allocated a score of 0. The preoperative FA score was significantly associated with tumor length, depth of invasion, lymph node involvement, tumor-node-metastasis (TNM) stage, and the modified Glasgow Prognostic Score (mGPS). No significant differences in age, gender, tumor location, degree of differentiation, smoking or alcohol consumption were found between groups. Univariate survival analysis revealed that high preoperative FA score (1/2) was significantly associated with unfavorable disease-free survival (DFS) [hazard ratio (HR), 1.675; 95% confidence interval (CI), 1.278-2.195; P < 0.001] and overall survival (OS) (HR, 1.685; 95% CI, 1.268-2.239; P < 0.001). Furthermore, it remained an independent prognostic indicator for both DFS (HR, 1.394; 95% CI, 1.035-1.879; P = 0.029) and OS (HR, 1.369; 95% CI, 1.010-1.878; P = 0.048) in multivariable Cox regression analysis. A high preoperative FA score could significantly predict impaired long-term survival for ESCC patients who underwent transthoracic esophagectomy.

Confirming the multidimensionality of psychological well-being among Korean immigrant mothers in the United States.

Ryff's Psychological Well-Being (PWB) Scale is a theoretically derived instrument that focuses on six dimensions of eudaimonic well-being. Although the PWB scale has been widely used in both clinical and general samples with different sociodemographic characteristics, its factor structure within first-generation Korean immigrant mothers require examination, as they often face socio-cultural challenges due to immigration (e.g., experiencing acculturation stress, being socially and culturally segregated, following heritage cultural obligations to be a "wise mother and good wife," taking less prestige jobs, etc.) that could negatively influence their well-being. This study examined the factor structure of an 18-item version of the PWB Scale in a sample of 169 first-generation Korean immigrant mothers of young children in the U.S. A second-order confirmatory factor analysisdid not support the original factor structure of the PWB scale. More importantly, high correlations among some of the PWB subscales suggested that the PWB factors may not be distinct from each other and the number of factors should be reduced. Exploratory factor analysis was conducted on the four highly correlated factors in subsequent analyses and three new factors (Satisfaction with Life, Goal Orientation, and Positive Self-Perceptions) were identified. The newly derived PWB factors were negativelycorrelated with mothers' depressive symptoms.These findings advanced our understanding of psychological well-being in first-generation Korean immigrant mothersand highlighted the need to consider socio-cultural factors in mental health research on this population.

Silencing of perilipin by short hairpin RNA inhibits proliferation and induces apoptosis in liposarcoma cells.

Previous studies have identified that perilipin-1 (PLIN1) is a highly specific marker for liposarcoma. However, its functions have yet to be fully elucidated. The aim of the present study was to investigate the potential role of PLIN1 in the proliferation, migration and apoptosis of liposarcoma cells. Short hairpin RNA was designed to inhibit PLIN1 levels. Cell proliferation was monitored by Cell Counting Kit­8 assay and cell migration determined by wound healing assay. Flow cytometry was performed to assess the cell cycle distributions and apoptosis in liposarcoma cells. The results demonstrated that the expression of PLIN1 was significantly upregulated in liposarcoma tumor tissues compared with normal adipose tissues. Silencing of PLIN1 by short hairpin RNA significantly inhibited proliferation and migration and induced G1 phase cell cycle arrest and apoptosis in liposarcoma cell lines. It was identified that PLIN1 serves a crucial role in the pathogenesis and progression of liposarcoma and may be a potential therapeutic target for its clinical management.

Trastuzumab modified silica nanoparticles loaded with doxorubicin for targeted and synergic therapy of breast cancer.

Untargeted delivery as well as low efficacy are two main obstacles for effective breast cancer therapy. Here in this study, we surface modified silica nanoparticles (SLN) with Trastuzumab (Tra) to construct a tumor-targeting carrier (Tra-SLN) for specific drug delivery to human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells. In addition, Tra-SLN could also loaded with broad-spectrum anticancer drug doxorubicin (DOX) to finally construct a drug delivery system (DDS) capable of co-delivering Tra and DOX (Tra-SLN/DOX). Our results demonstrated that the as-prepared Tra-SLN/DOX was nanoscale particles with spheroid appearance which showed preferable stability in physiological environments. In addition, the Tra-SLN/DOX could specifically target to HER2 overexpressed MCF-7 cells. Both in vitro and in vivo experiments revealed that the Tra-SLN/DOX exerted enhanced anticancer efficacy when compared with Tra or DOX alone. It was suggested that Tra-SLN/DOX might be a promising platform for enhanced therapy of breast cancer.

A novel DMD splicing mutation found in a family responsible for X-linked dilated cardiomyopathy with hyper-CKemia.

This study was aimed to detect a new mutation responsible for X-linked dilated cardiomyopathy with hyper-CKemia.We studied a proband who presented with cardiac symptoms with hyper-CKemia, but no clinical skeletal involvement in physical examination, laboratory tests, electromyography, echocardiography, and magnetic resonance imaging (MRI) of cardiac muscles. Muscle biopsy for histopathology and immunohistochemistry for accessing sarcolemma changes. The next-generation sequencing and bioinformatics analysis were performed on the patient and Sanger sequencing was confirmed on the other 6 unaffected families.The clinic investigations illustrated a dilated cardiomyopathy. Histopathology and immunohistochemistry showed dystrophic changes and an obvious reduction of dystrophin-N and δ-sarcoglycan, respectively. One hemizygous splicing pathogenic mutation c.31 + 1G > C of exon 1 in the DMD gene (chrX33229398, NM_00 4006) was finally identified in the patient and his nephew, but it was carried in his mother and sister.A novel small mutation was identified at the first exon-intron boundary splicing site by next-generation sequencing and bioinformatics analysis.