GNAS gene mutations affecting XLαs and bone health: A long neglected relationship.

The GNAS locus is an imprinted site. The α-subunit of the stimulatory G protein (Gsα) and extralarge variant (XLαs) are the two important products of the GNAS locus. The abnormal expression of Gsα is associated with pseudohypoparathyroidism (PHP) and related disorders, including Albright hereditary osteodystrophy (AHO), pseudopseudohypoparathyroidism (PPHP), and progressive osseous heteroplasia (POH). XLαs protein can mimic the catalytic intracellular synthesis of cyclic adenosine monophosphate (cAMP) by Gsα in response to parathyroid hormone (PTH) stimulation, which may be involved in the pathogenesis of PPHP and POH in patients with paternal GNAS defects. A paternally inherited nonsense variant in the first exon of XLαs in an adult patient may be associated with fractures and osteopetrosis. The relationship between the XLαs product of the GNAS locus and bone remodeling may have been overlooked. Here, we summarize the phenotypes of genetic mouse models and clinical cases of XLαs variations and suggest that the abnormal paternal expression of XLαs may be associated with the development of POH and affect osteoblast and osteoclast differentiation.

Clinical efficacy analysis of oocyte cryopreservation: A propensity score matched study.

OBJECTIVE: To investigate the effectiveness of oocyte thawing cycles in the clinical application of assisted reproductive technology (ART). STUDY DESIGN: The clinical data of 78 cases who underwent oocyte thawing cycles in our center were retrospectively analyzed. All patients in this study received oocyte cryopreservation for the husband reason. According to patient age at egg freezing, patients were divided into three observation groups (Group A, <30 years old; Group B, 30-34 years old; Group C, ≥35 years old), and the control groups were selected by propensity score matching with fresh cycles. The clinical outcomes of each group were compared, and the clinical efficacy of oocyte thawing cycles was analyzed. RESULTS: Clinical pregnancy outcomes of oocyte thawing cycles were not significantly different from that of fresh oocytes, but vitrification affected the number of two pronuclei zygotes developing to cleavage stage and the number of high-quality embryos, and the normal fertilization rate after thawing. The cycle cumulative live birth rate in Group C was significantly lower than those in Groups A and B. The live birth rates per egg of Groups A, B, C were 5.03%, 5.61%, and 3.57%, respectively, and the numbers of eggs per live birth were 13.72, 14.43, and 21.0, respectively. CONCLUSIONS: The overall clinical outcomes of oocyte vitrification were similar to that of fresh oocytes, but the cleavage rate and embryo quality of frozen oocytes were slightly reduced. Freezing of oocytes in women over 35 years of age affects the clinical efficacy of ART.

Bone marrow adipocytes and lung cancer bone metastasis: unraveling the role of adipokines in the tumor microenvironment.

Bone is a common site of metastasis for lung cancer. The "seed and soil" hypothesis suggests that the bone marrow microenvironment ("soil") may provide a conducive survival environment for metastasizing tumor cells ("seeds"). The bone marrow microenvironment, comprising a complex array of cells, includes bone marrow adipocytes (BMAs), which constitute about 70% of the adult bone marrow volume and may play a significant role in tumor bone metastasis. BMAs can directly provide energy for tumor cells, promoting their proliferation and migration. Furthermore, BMAs participate in the tumor microenvironment's osteogenesis regulation, osteoclast(OC) regulation, and immune response through the secretion of adipokines, cytokines, and inflammatory factors. However, the precise mechanisms of BMAs in lung cancer bone metastasis remain largely unclear. This review primarily explores the role of BMAs and their secreted adipokines (leptin, adiponectin, Nesfatin-1, Resistin, chemerin, visfatin) in lung cancer bone metastasis, aiming to provide new insights into the mechanisms and clinical treatment of lung cancer bone metastasis.

Development of a nomogram to predict the risk of secondary failure of platelet recovery in patients with ß-thalassemia major after hematopoietic stem cell transplantation: a retrospective study.

Background: Secondary failure of platelet recovery (SFPR) is a common complication that influences survival and quality of life of patients with ß-thalassemia major (ß-TM) after hematopoietic stem cell transplantation (HSCT). Objectives: A model to predict the risk of SFPR in ß-TM patients after HSCT was developed. Design: A retrospective study was used to develop the prediction model. Methods: The clinical data for 218 ß-TM patients who received HSCT comprised the training set, and those for another 89 patients represented the validation set. The least absolute shrinkage and selection operator regression algorithm was used to identify the critical clinical factors with nonzero coefficients for constructing the nomogram. Calibration curve, C-index, and receiver operating characteristic curve assessments and decision curve analysis (DCA) were used to evaluate the calibration, discrimination, accuracy, and clinical usefulness of the nomogram. Internal and external validation were used to test and verify the predictive model. Results: The nomogram based on pretransplant serum ferritin, hepatomegaly, mycophenolate mofetil use, and posttransplant serum albumin could be conveniently used to predict the SFPR risk of thalassemia patients after HSCT. The calibration curve of the nomogram revealed good concordance between the training and validation sets. The nomogram showed good discrimination with a C-index of 0.780 (95% CI: 70.3-85.7) and 0.868 (95% CI: 78.5-95.1) and AUCs of 0.780 and 0.868 in the training and validation sets, respectively. A high C-index value of 0.766 was reached in the interval validation assessment. DCA confirmed that the nomogram was clinically useful when intervention was decided at the possibility threshold ranging from 3% to 83%. Conclusion: We constructed a nomogram model to predict the risk of SFPR in patients with ß-TM after HSCT. The nomogram has a good predictive ability and may be used by clinicians to identify SFPR patients early and recommend effective preventive measures.

Identification of a Novel Cuproptosis-Related Gene Signature in Eutopic Endometrium of Women with Endometriosis.

Endometriosis (EMs) is a life-long endocrine disorder and a common cause for female infertility and pelvic pain. The key characteristics of eutopic endometrium of EMs patients are high proliferative and migratory potentials. Cuproptosis is a recently identified copper- and-mitochondrial-dependent regulated cell death. Regretfully, its role in EMs remains unclear. In this study, Kyoto Encyclopedia of Genes and Genomes analyses of differentially expressed genes (DEGs) indicated strong activation of the PI3K-Akt-mTOR pathway and biological process analysis reported positive regulation of kinase activity. Next, we screened 11 cuproptosis-related DEGs and found all of them were downregulated in the EMs group, which indicated the suppression of cuproptosis in EMs. One key cuproptosis-related gene, PDHA1, was selected via support vector machine, random forest algorithm and lasso regularization to build a risk-scoring model, which was tested in both internal and external validations. In conclusion, the downregulation and kinase activity of PDHA1 may function with the PI3K-Akt-mTOR pathway in some way, which could suppress the cuproptosis level and account for the cancer-like pathology in EMs.

Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell resolution.

Background: Diffuse large B-cell lymphoma (DLBCL) represents the most prevalent form of aggressive non-Hodgkin lymphoma. Despite receiving standard treatment, a subset of patients undergoes refractory or recurrent cases, wherein the involvement of cancer stem cells (CSCs) could be significant. Methods: We comprehensively characterized B cell subpopulations using single-cell RNA sequencing data from three DLBCL samples and one normal lymph tissue. The CopyKat R package was employed to assess the malignancy of B cell subpopulations based on chromosomal copy number variations. CIBERSORTx software was utilized to estimate the proportions of B cell subpopulations in 230 DLBCL tissues. Furthermore, we employed the pySCENIC to identify key transcription factors that regulate the functionality of B cell subpopulations. By employing CellphoneDB, we elucidated the interplay among tumor microenvironment components within the B cell subpopulations. Finally, we validated our findings through immunofluorescence experiments. Results: Our analysis revealed a specific cancer stem cell-like B cell subpopulation exhibiting self-renewal and multilineage differentiation capabilities based on the exploration of B cell subpopulations in DLBCL and normal lymph tissues at the single-cell level. Notably, a high infiltration of cancer stem cell-like B cells correlated with a poor prognosis, potentially due to immune evasion mediated by low expression of major histocompatibility complex molecules. Furthermore, we identified key transcription factor regulatory networks regulated by HMGB3, SAP30, and E2F8, which likely played crucial roles in the functional characterization of the cancer stem cell-like B cell subpopulation. The existence of cancer stem cell-like B cells in DLBCL was validated through immunofluorescent staining. Finally, cell communication between B cells and tumor-infiltrating T cell subgroups provided further insights into the functional characterization of the cancer stem cell-like B cell subpopulation. Conclusions: Our research provides a systematic description of a specific cancer stem cell-like B cell subpopulation associated with a poor prognosis in DLBCL. This study enhances our understanding of CSCs and identifies potential therapeutic targets for refractory or recurrent DLBCL patients.

Oxytocin Impairs the Recognition of Micro-Expressions of Surprise and Disgust.

As fleeting facial expressions which reveal the emotion that a person tries to conceal, micro-expressions have great application potentials for fields like security, national defense and medical treatment. However, the physiological basis for the recognition of these facial expressions is poorly understood. In the present research, we utilized a double-blind, placebo-controlled, mixed-model experimental design to investigate the effects of oxytocin on the recognition of micro-expressions in three behavioral studies. Specifically, in Studies 1 and 2, participants were asked to perform a laboratory-based standardized micro-expression recognition task after self-administration of a single dose of intranasal oxytocin (40 IU) or placebo (containing all ingredients except for the neuropeptide). In Study 3, we further examined the effects of oxytocin on the recognition of natural micro-expressions. The results showed that intranasal oxytocin decreased the recognition speed for standardized intense micro-expressions of surprise (Study 1) and decreased the recognition accuracy for standardized subtle micro-expressions of disgust (Study 2). The results of Study 3 further revealed that intranasal oxytocin administration significantly reduced the recognition accuracy for natural micro-expressions of surprise and disgust. The present research is the first to investigate the effects of oxytocin on micro-expression recognition. It suggests that the oxytocin mainly plays an inhibiting role in the recognition of micro-expressions and there are fundamental differences in the neurophysiological basis for the recognition of micro-expressions and macro-expressions.

Health-related quality of life in pediatric patients with ß-thalassemia major after hematopoietic stem cell transplantation.

Our main purpose was to evaluate health-related quality of life (HRQOL) in ß-thalassemia major patients who underwent transplantation from September 2012 to November 2019. The PedsQL 4.0 scale proxy version was administered to 221 transplant patients aged 5-18 years. Their HRQOL results in the proxy-report were compared with those in the proxy-report of 429 matched healthy peers and 198 matched nontransplant patients. Compared with their healthy peers, the transplant patients exhibited worse HRQOL in the physical health domain (P < 0.001), school domain (P < 0.001) and overall scores (P = 0.006). Patients within 4 years after transplantation exhibited physical functioning (P < 0.001), school functioning (P < 0.001) and overall HRQOL damage (P = 0.001); the scores across all domains for patients more than 4 years after transplantation were not significantly different from those for the healthy controls. The transplant patients rated their HRQOL for all domains better than the nontransplant patients (P < 0.001). The HRQOL of patients after human leukocyte antigen (HLA)-matched related and HLA-matched unrelated donor transplantation were not significantly different. Chronic graft-versus-host disease and two or more comorbidities were independently negatively associated with overall HRQOL outcomes (P = 0.032 and P < 0.001, respectively). In conclusion, patients more than 4 years after transplantation achieve an HRQOL equal to that of their healthy peers.

An ingroup disadvantage in recognizing micro-expressions.

Micro-expression is a fleeting facial expression of emotion that usually occurs in high-stake situations and reveals the true emotion that a person tries to conceal. Due to its unique nature, recognizing micro-expression has great applications for fields like law enforcement, medical treatment, and national security. However, the psychological mechanism of micro-expression recognition is still poorly understood. In the present research, we sought to expand upon previous research to investigate whether the group membership of the expresser influences the recognition process of micro-expressions. By conducting two behavioral studies, we found that contrary to the widespread ingroup advantage found in macro-expression recognition, there was a robust ingroup disadvantage in micro-expression recognition instead. Specifically, in Study 1A and 1B, we found that participants were more accurate at recognizing the intense and subtle micro-expressions of their racial outgroups than those micro-expressions of their racial ingroups, and neither the training experience nor the duration of micro-expressions moderated this ingroup disadvantage. In Study 2A and 2B, we further found that mere social categorization alone was sufficient to elicit the ingroup disadvantage for the recognition of intense and subtle micro-expressions, and such an effect was also unaffected by the duration of micro-expressions. These results suggest that individuals spontaneously employ the social category information of others to recognize micro-expressions, and the ingroup disadvantage in micro-expression stems partly from motivated differential processing of ingroup micro-expressions.

Folic Acid Preconditioning Alleviated Radiation-Induced Ovarian Dysfunction in Female Mice.

Radiological therapy/examination is the primary source of artificial radiation exposure in humans. While its application has contributed to major advances in disease diagnosis and treatment, ionizing radiation exposure is associated with ovarian damage. The use of natural products, either alone or as an adjunct, has become increasingly common for reducing the side effects of radiological therapy during disease treatment. Herein, we explored the protective effect of folic acid (FA), a widely used B vitamin, against radiation-induced ovarian injury and its mechanism of action. Female mice with normal ovarian function were randomly divided into control, FA, radiation, and radiation + FA groups. The intervention strategy included daily intragastric administration of FA (5 mg/kg) for 3 weeks prior to radiation exposure. Mice in the radiation and radiation + FA groups received a single dose of 5 Gy X-ray irradiation. Changes in the estrous cycle were then recorded, and ovarian tissues were collected. Pathophysiological changes as well as reproductive and endocrine-related indexes were determined via H&E staining, immunohistochemistry, Western blot, and ELISA. The reproductive performance and emotional symptoms of animals were also monitored. Our results indicated that FA intervention effectively alleviated ovarian damage, leading to more regular estrous cycles, lesser impairment of follicular morphology and endocrine status, as well as greater germ cell preservation. Reduced levels of oxidative stress, inflammation, and enhanced DNA repair were associated these changes. FA pre-administration improved the reproductive performance, leading to higher pregnancy rates and greater litter sizes. Further, the anxiety levels of animals were significantly reduced. Our results indicate that FA pre-administration significantly alleviates radiation-induced ovarian damage in rodents, highlighting its potential as a protective strategy against radiation exposure in the female population.

Protective effect of Epicatechin on APAP-induced acute liver injury of mice through anti-inflammation and apoptosis inhibition.

Epicatechin (EC) is the most effective compound in Euonymus alatus (Thunb.)Sieb, and possesses a series of benefits, including anti-inflammatory, antioxidant, antiobesity and anticancer effects. In this study, we investigated the protective effects of EC in Acetaminophen(N-acetyl-p-aminophenol, APAP)-induced acute liver injury in C57BL/6J mice and explored the possible mechanisms involved in these effects.[Formula: see text].

Methyl 3,4-dihydroxybenzoate protects against d-galN/LPS-induced acute liver injury by inhibiting inflammation and apoptosis in mice.

OBJECTIVES: Aimed to investigate the effect and mechanism of methyl 3,4-dihydroxybenzoate (MDHB) on d-galactosamine/lipopolysaccharide (d-galN/LPS)-induced acute liver failure (ALF). METHODS: Confirmed the hepatoprotective effect and hepatotoxicity of MDHB by histopathological examination (HE) and examination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); the expression of serum tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) was detected by ELISA; transcription levels of TNF-α, IL-1ß, IL-6 and Toll-like receptor 4 (TLR4) were detected by qRT-PCR; and phosphorylation levels of p38 and p65 were analysed by Western blot. RESULTS: Histopathological examination and examination of ALT and AST confirmed that MDHB is a low toxicity drug that can resist d-galN/LPS-induced ALF; MDHB can effectively reduce high transcription and expression of TNF-α, IL-1ß, IL-6 and TLR4 in d-galN/LPS-induced ALF; and Western blot showed that MDHB could down-regulate the expression of bax, up-regulate the expression of bcl-xl and bcl-2, and inhibit the phosphorylation of p38 and p65. CONCLUSIONS: Methyl 3,4-dihydroxybenzoate can effectively resist d-galN/LPS-induced acute liver failure, which is related to the inhibition of inflammation and apoptosis.

[Protective effect of Ginkgo biloba extract on paracetamol-induced acute hepatic injury in mice].

OBJECTIVE: To investigate the protective effects of Ginkgo biloba extract(GBE) on paracetamol(APAP)-induced acute hepatic injury in mice and its mechanism. METHODS: Thirty mice were randomly divided into control group, model group, GBE low, medium and high-dose(50,100,and 200 mg·kg-1)groups,with 6 mice in each group. All mice except control group were administered with APAP(300 mg/kg)for one time by intraperitoneal injection. The mice in GBE low, medium and high-dose groups were intragastric administered with GBE for 2 d consecutively, then samples were harvested for analysis. The appearance and pathology of liver were observed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and the levels of superoxide dismutase (SOD), myeloperoxidase(MPO), glutathione (GSH) and malondialdehyde (MDA) in hepatic tissue were measured. Western blot was used to detect the protein expressions of Nrf2 and HO-1. RESULTS: Compared with control group, in model group, the appearance and pathology of liver were bad, the levels of ALT,AST,TNF-α and IL-6 in serum were increased significantly(P<0.01),the levels of GSH and SOD were decreased while the levels of MDA and MPO were increased in hepatic tissue(P<0.01), the expressions of Nrf2 and HO-1 were increased in hepatic tissue(P<0.05). Compared with model group, in GBE groups, the appearance and pathology of liver were improved, the levels of ALT,AST,TNF-α and IL-6 in serum were decreased significantly(P<0.01), the levels of GSH and SOD were increased while the levels of MDA and MPO were decreased in hepatic tissue(P<0.01), the expression of Nrf2 and HO-1 were increased in hepatic tissue(P<0.05). The high-dose of GBE possessed the most obvious treatment effect among them. CONCLUSIONS: GBE may play a protective role in APAP-induced acute hepatic injury through Nrf2/HO-1 pathway.