Analysis of the causal relationship between gut microbiota and bone remodeling growth factor from the gene association.

BACKGROUND: A growing body of evidence indicates a close association between the gut microbiota (GM) and the bone remodeling (BR) process, raising suspicions that the GM may actively participate in BR by modulating the levels of growth factors. However, the precise causal relationship between them remains unclear. Due to many confounding factors, many microorganisms related to BR growth factors have not been identified. We aimed to elucidate the causal relationship between the GM and BR growth factors. METHODS: We evaluated the genome-wide association study (GWAS) summary statistics for GM and five common growth factors associated with BR: namely, bone morphogenetic proteins (BMP), transforming growth factors(TGF), insulin growth factors (IGFs), epidermal growth factors (EGFs), and fibroblast growth factors (FGF). The causal relationship between the GM and BR growth factors was studied by double-sample Mendelian randomized analysis. We used five Mendelian randomization (MR) methods, including inverse variance-weighted (IVW), MR-Egger, simple mode, weighted median, and weighted model methods. RESULTS: Through MR analysis, a total of 56 bacterial genera were co-identified as associated with BMP, TGF, IGF, EGF, and FGF. Among them, eight genera were found to have a causal relationship with multiple growth factors: Marvinbryantia was causally associated with BMP-6 (P = 0.018, OR = 1.355) and TGF-ß2 (P = 0.002, OR = 1.475); Lachnoclostridium, BMP-7 (P = 0.021, OR = 0.73) and IGF-1 (P = 0.046, OR = 0.804); Terrisporobacter, TGF-ß (P = 0.02, OR = 1.726) and FGF-23 levels (P = 0.016, OR = 1.76); Ruminiclostridium5, TGF-ß levels (P = 0.024, OR = 0.525) and FGFR-2 (P = 0.003, OR = 0.681); Erysipelatoclostridium, TGF-ß2 (P = 0.001, OR = 0.739) and EGF and its receptor (EGFR) (P = 0.012, OR = 0.795); Eubacterium_brachy_group, FGFR-2 (P = 0.045, OR = 1.153) and EGF (P = 0.013, OR = 0.7); Prevotella9 with EGFR (P = 0.022, OR = 0.818) and FGFR-2 (P = 0.011, OR = 1.233) and Faecalibacterium with FGF-23 (P = 0.02, OR = 2.053) and IGF-1 (P = 0.005, OR = 0.843). CONCLUSION: We confirmed the causal relationship between the GM and growth factors related to BR, which provides a new perspective for the study of BR, through targeted regulation of specific bacteria to prevent and treat diseases and growth factor-mediated BR disorders.

The association between hemoglobin level and sarcopenia in Chinese patients with Crohn's disease.

Sarcopenia and anemia are common complications in patients with Crohn's Disease (CD). However, few studies have shown the association between sarcopenia and hemoglobin levels in CD patients. This retrospective study aimed to explore such association in Chinese patients with CD. Two hundred and twelve adult CD inpatients who underwent computed tomography (CT) or magnetic resonance imaging (MRI) examinations from July 2019 to December 2021 were included in the study. Sarcopenia was defined according to the cutoff value of skeletal muscle index of lumbar spine 3 (SMI-L3) (< 44.77cm2/m2 for males and < 32.5cm2/m2 for females). The CD patients were divided into two groups based on the presence or absence of sarcopenia. Clinical data, hemoglobin levels, and other laboratory data were retrospectively collected. The association between hemoglobin levels and sarcopenia was analyzed by univariable and multivariable logistic regression analysis. Sarcopenia occurred in 114 CD patients (53.8%). Compared to patients without sarcopenia, patients with sarcopenia had a lower proportion of L1 (30.7% vs. 45.8%, p = 0.032) and B1 classification (58.8% vs. 72.4%, p = 0.037). Patients with sarcopenia had significantly lower levels of hemoglobin (Hb) (116.5 ± 22.8 vs. 128.1 ± 21.0, p < 0.001). The prevalence of sarcopenia increased with the decrease in hemoglobin level (p for trend < 0.05). Linear regression analysis showed that hemoglobin levels were associated with SMI-L3 (ß = 0.091, p = 0.001). Multivariable logistic regression analysis found that higher hemoglobin levels (OR:0.944; 95% CI: 0.947,0.998; p = 0.036) were independent protective factors for sarcopenia. Lower hemoglobin levels are independently associated factors of sarcopenia in adult Chinese patients with CD.

Construction of a prognostic risk score model based on the ARHGAP family to predict the survival of osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignancy of bone tumors. More and more ARHGAP family genes have been confirmed are to the occurrence, development, and invasion of tumors. However, its significance in osteosarcoma remains unclear. In this study, we aimed to identify the relationship between ARHGAP family genes and prognosis in patients with OS. METHODS: OS samples were retrieved from the TCGA and GEO databases. We then performed LASSO regression analysis and multivariate COX regression analysis to select ARHGAP family genes to construct a risk prognosis model. We then validated this prognostic model. We utilized ESTIMATE and CIBERSORT algorithms to calculate the stroma and immune scores of samples, as well as the proportions of tumor infiltrating immune cells (TICs). Finally, we conducted in vivo and in vitro experiments to investigate the effect of ARHGAP28 on osteosarcoma. RESULTS: We selected five genes to construct a risk prognosis model. Patients were divided into high- and low-risk groups and the survival time of the high-risk group was lower than that of the low-risk group. The high-risk group in the prognosis model constructed had relatively poor immune function. GSEA and ssGSEA showed that the low-risk group had abundant immune pathway infiltration. The overexpression of ARHGAP28 can inhibit the proliferation, migration, and invasion of osteosarcoma cells and tumor growth in mice, and IHC showed that overexpression of ARHGAP28 could inhibit the proliferation of tumor cells. CONCLUSION: We constructed a risk prognostic model based on five ARHGAP family genes, which can predict the overall survival of patients with osteosarcoma, to better assist us in clinical decision-making and individualized treatment.

The association between jaundice and poorly differentiated pancreatic neuroendocrine neoplasms (Ki67 index > 55.0%).

BACKGROUND: Jaundice occurs in some pancreatic disease. However, its occurrences and role in pancreatic neuroendocrine neoplasms (PNENs) has not been well studied. In this study we showed the association between jaundice and the risk of high grade and poorly differentiated PNENs. METHODS: Ninety-three patients with head-neck PNENs were included. Poorly differentiated pancreatic neuroendocrine neoplasms were defined by a ki67 index > 55.0%. Logistic regression was used to show the association between demographic information, clinical signs and symptoms and the risk of poorly differentiated tumors. A nomogram model was developed to predict poorly differentiated tumor. RESULTS: Eight of 93 PNEN patients (8.6%) had jaundice. The age and ki67 index in patients with jaundice were significantly higher than those patients without jaundice. All jaundice occurred in patients with grade 3 PNENs. Mutivariable regression analysis showed that age (odds ratio(OR) = 1.10, 95% confidence interval (CI):1.02-1.19), tumor size (OR = 1.42, 95%CI:1.01-2.00) and jaundice (OR = 14.98, 95%CI: 1.22-184.09) were associated with the risk of poorly differentiated PNENs. The age and size combination showed a good performance in predicting poorly differentiated PNENs (area under the curve (AUC) = 0.81, 95% CI: 0.71-0.90). The addition of jaundice further improved the age- and size-based model (AUC = 0.86, 95% CI: 0.78-0.91). A nomogram was developed based on age, tumor size and jaundice. CONCLUSION: Our data showed that jaundice was associated with the risk of high grade PNENs and poorly differentiated PNENs.

Amorphous hollow manganese silicate nanosphere oxidase mimic for ultrasensitive and high-reliable colorimetric detection of biothiols.

Metal-based nanozymes with exceptional physicochemical property and intrinsic enzymatic properties have been widely used in industrial, medical, and diagnostic fields. However, low substrate affinity results in unsatisfying catalytic kinetic and instability in complicated conditions, which significantly decreases their sensitivity and reliability. Herein, an amorphous hollow manganese silicate nanosphere (defined as AHMS) has been successfully synthesized via a facile one-step hydrothermal method and utilized in the archetype for colorimetric detection of biothiols with high sensitivity and high reliability. The experimental data demonstrates that ultrafast affinity of the substrate contributes to enhanced sensitivity with outstanding catalytic kinetic features (Km = 27.1 µM) and low limit of detection (LODGSH = 20 nM). The designed sensor demonstrates a reliable applicability for analysis of biological liquids (fetal calf serum and Staphylococcus aureus) and design of visual logic gates. Therefore, AHMS provides a promising strategy for ultrasensitive and high-reliable biosensing.

Interface coupling and charge doping in graphene on ferroelectric BiAlO3(0001) polar surfaces.

The ferroelectric field-effect transistors (FeFETs) based on graphene/ferroelectric (Gr/FE) hybrid systems have been attracting a lot of attention in recent years. The interface interaction and charge transfer between graphene and the ferroelectric substrates are important factors that determine the performance of graphene-based FeFETs. According to our intuitive sense, the electrostatically doped carriers in graphene on the ferroelectric positive and negative surfaces should be n-type and p-type, respectively. In the present work, however, by employing first-principles density functional theory (DFT) calculations, we reveal that an unusual charge doping effect occurs in graphene on the thermodynamically preferred ferroelectric BiAlO3(0001) polar surfaces. The graphene on the BiAlO3(0001) positive surface is electrostatically doped p-type, while the BiAlO3(0001) negative surface induces n-type carriers in the graphene overlayer. Further analysis demonstrates that, although the electrostatic doping effect in the Gr/FE system depends on the polarization direction of the ferroelectric substrate, the resultant carrier type and density in graphene are determined by the specific band arrangement between graphene and the ferroelectric polar surface. In addition to the graphene-based FeFETs, our results predict that the Gr/BiAlO3(0001) systems can be used to fabricate graphene p-n homojunctions by engineering the domain pattern in the ferroelectric substrate.

MicroRNA-146a negatively regulates IL-33 in activated group 2 innate lymphoid cells by inhibiting IRAK1 and TRAF6.

Type II innate lymphoid cells (ILC2) play a very important role in the pathogenesis of allergic asthma. This study aims to investigate whether miR-146a inhibition of asthma is related with interleukin (IL)-33 signaling path way in ILC2 and the underlying mechanisms. Asthma mice model was induced by ovalbumin. miRNA146a mimics was administrated to asthma mice or transfected to activated ILC2 purified from asthma mice lung. RT-PCR was used to detect miRNA146a level in lung tissue and ILC2. IL-5 and IL-13 levels in culture supernatant were detected by flow cytometry. Interleukin-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6), signal transducer and activator of transcription 1 (STAT1) protein expression levels were detected by western blot. miR-146a directly inhibited ILC2 function and suppressed ILC2 proliferation both in vivo and in vitro. During stimulation of ILC2, miR-146a expression gradually increased with a decrease of cell proliferation. Modulation of ILC2 function by miR-146a may depend on IL-33/interleukin 1 receptor-like 1 (IL1RL1 or ST2) signaling through inhibiting IRAK1 and TRAF6.miR-146a can inhibit IRAK1 and TRAF6, downstream molecules of ST2 signal pathway, thereby negatively regulate IL-33/ST2-activated ILC2 to inhibit asthma. Targeting miR-146 maybe a novel strategy for the treatment of allergic asthma.

Development and validation of a seven-immune-feature-based prognostic score for oral squamous cell carcinoma after curative resection.

Immune infiltrates have been increasingly recognized as robust prognostic factors for human cancer. Here, we developed and validated a seven-immune-feature-based prognostic score (7IFBPS) for patients with oral squamous cell carcinoma (OSCC) after curative resection. Fourteen immune features regarding detailed locations and densities of seven types of tumor-infiltrating immune cells (TIIs) were characterized in clinical samples from 269 eligible patients in three independent cohorts by immunohistochemistry coupled with digital quantitation. Optimal cutoff values for individual immune features were yielded using X-tile software. The 7IFBPS was constructed by Kaplan-Meier and Cox regression model in training cohort and verified in testing, validation and combined cohorts. Concordance index (C-index), receiver operating characteristics and calibration curves were employed to define the performance of 7IFBPS in prognostic prediction. High CD3 IM (invasive margin), CD3 CT (center of tumor), CD8 CT, CD45RO IM, CD45RO CT, FOXP3 IM and FOXP3 CT significantly associated with improved survival. The 7IFBPS score was calculated using the formula: 1.041 × CD3 IM + 1.24 × CD3 CT + 1.701 × CD8 CT + 1.127 × CD45RO IM + 1.348 × CD45RO CT + 1.089 × FOXP3 IM + 1.483 FOXP3 CT. High 7IFBPS significantly associated with improved survival in all cohorts and served as an independent prognostic predictor. The C-index of 7IFBPS for predicting survival was 0.668 (95% CI, 0.609-0.726). Calibration curves for survival probability showed good agreement between prediction by 7IFBPS and actual observation. Collectively, our findings established the 7IFBPS as a novel powerful prognostic classifier for resectable OSCC. It holds potentials to be incorporated into current prognostic regime to better patient stratification.

[Comparison of the repair effects of Haiao oral biofilm alone or in combination with allogeneic bone graft in bone defects after jaw bone cyst surgery].

PURPOSE: To compare the repair effects of Haiao oral biofilm alone or in combination with allogeneic bone graft on bone defects after jaw bone cyst surgery. METHODS: A prospective study was conducted on 105 patients with bone defects after jaw bone cyst surgery who were admitted to Affiliated Hospital of Jiangnan University from November 2020 to July 2022. According to the random number table methods, the patients were divided into three groups: Haiao membrane group, allogeneic bone graft group and combination group. Among them, Haiao membrane group(35 patients) were repaired using Haiao oral biofilm; allogeneic bone group(35 patients) using allogeneic bone, while combined group (35 patients) using a combination of Haiao oral biofilm and allogeneic bone graft. The clinical basic data of three groups of patients were compared, including the healing effect at the incision, bone density at the bone defect, bone resorption and attachment loss. Statistical analysis was performed with SPSS 22.0 software package. RESULTS: There was no significant difference in general clinical data among the three groups (P＞0.05). The postoperative restoration effect of gingival soft tissue morphology in combined group was significantly better than that in Haiao membrane group and allogeneic bone graft group (P＜0.05). There was no significant difference in bone density at the bone defect site among the three groups before treatment(P＞0.05); 6 and 12 months after treatment, the bone density of the three groups was significantly improved (P＜0.05), and combined group was significantly higher than the other groups(P＜0.05). There was no significant difference in the vertical and lingual bone resorption levels among the three groups before treatment(P＞0.05); 6 and 12 months after treatment, the vertical and lingual bone resorption levels of the three groups were significantly reduced (P＜0.05), and combined group were significantly lower than the other groups (P＜0.05). There was no significant difference in attachment loss among the three groups before treatment(P＞0.05); 6 and 12 months after treatment, the attachment loss of the three groups decreased(P＜0.05), and combined group was significantly lower than the other groups(P＜0.05). CONCLUSIONS: The combination of Haiao oral biofilm and allogeneic bone graft has good repair effect in the treatment of bone defects after jaw bone cyst surgery, which is beneficial for the recovery of gingival soft tissue, improvement of bone density, reduction of bone resorption and attachment loss.

The Association Between Environmental Cadmium Exposure and Parathyroid Hormone Levels.

Cadmium exposure is associated with renal dysfunction and bone damage. Chronic kidney disease and bone loss are also related to parathyroid hormone (PTH). However, whether cadmium exposure affect PTH level is not completely understood. In this study, we observed the association between environmental cadmium exposure and PTH levels in a Chinese population. A ChinaCd study was performed in China in 1990s which included 790 subjects living in heavily, moderately and low cadmium polluted area. 354 of them (121 men and 233 women) also had the data of serum PTH. The cadmium levels in blood (BCd) and urine (UCd) were determined by flame atomic absorption spectrometry. Serum PTH was detected by immunoradiometric assay. Renal function was assessed based on urinary N-acetyl-ß-d-glucosaminidase (UNAG), ß2-microglobulin (UBMG) and urinary albumin (UALB). The median BCd and UCd levels were 4.69 µg/L and 5.50 µg/g creatinine. The BCd, UCd, UNAG, UBMG and UALB levels in subjects with low PTH (< 5.0 ng/L) were significantly higher than those with PTH ≥ 5.0 ng/L (p < 0.05 or p < 0.01). Spearman correlation analysis also showed that UCd level was negatively correlated to PTH levels (r = -0.17, p = 0.008) in women. A weak correlation was also observed between PTH level and BCd in women (r = -0.11, p = 0.09) and UBMG in total population (r = -0.114, p = 0.07). Univariable and mutivariable logistic regression analysis both demonstrated that high BCd (> 10 µg/L) (odds ratio (OR) = 2.26, 95% confidence interval (CI):1.10-4.63; OR = 2.36, 95%CI: 1.11-5.05) and UCd level (> 20 µg/g cr) (OR = 2.84, 95% CI:1.32-6.10; OR = 2.97, 95%CI: 1.25-7.05) were associated with high risk of low PTH. Our data showed that environmental cadmium exposure was associated with low PTH level.

Surface functionalization of calcium magnesium phosphate cements with alginate sodium for enhanced bone regeneration via TRPM7/PI3K/Akt signaling pathway.

Although calcium­magnesium phosphate cements (CMPCs) have been widely applied to treating critical-size bone defects, their repair efficiency is unsatisfactory owing to their weak surface bioactivity and uncontrolled ion release. In this study, we lyophilized alginate sodium (AS) as a coating onto HAp/K-struvite (H@KSv) to develop AS/HAp/K-struvite (AH@KSv), which promotes bone regeneration. The compressive strength and hydrophilicity of AH@KSv significantly improved, leading to enhanced cell adhesion in vitro. Importantly, the SA coating enables continuous ions release of Mg2+ and Ca2+, finally leading to enhanced osteogenesis in vitro/vivo and different patterns of new bone ingrowth in vivo. Furthermore, these composites increased the expression levels of biomarkers of the TRPM7/PI3K/Akt signaling pathway via an equilibrium effect of Mg2+ to Ca2+. In conclusion, our study provides novel insights into the mechanisms of Mg-based biomaterials for bone regeneration.

Assessing Thoracic Vertebral Bone Mineral Density (T8-T10) for Osteoporosis Diagnosis During CT Lung Cancer Screening in Older Adults.

Introduction: Osteoporosis diagnosis often utilizes quantitative computed tomography (QCT). This study explored the validity of applying lumbar bone mineral density (LBMD) standards to thoracic vertebrae (T8-T10) for osteoporosis detection during CT lung cancer screenings. This study investigated the utility of thoracic BMD (BMD-T8-T10) for detecting osteoporosis in older persons during CT lung cancer screening. Methods: We studied 701 participants who underwent QCT scans for both LBMD and BMD-T8-T10. Osteoporosis was diagnosed using ACR criteria based on LBMD. We determined BMD-T8-T10 thresholds via a receiver operating characteristic (ROC) curve and translated BMD-T8+T9+T10 to LBMD (TTBMD) using linear regression. Kappa test was used to evaluate the accuracy of BMD-T8-T10 thresholds and TTBMD in diagnosing osteoporosis. Results: Raw BMD-T8-T10 poorly identified osteoporosis (kappa = 0.51). ROC curve analysis identified BMD-T8-T10 thresholds for osteopenia (138 mg/cm3) and osteoporosis (97 mg/cm3) with areas under the curve of 0.97 and 0.99, respectively. We normalized BMD-T8-T10 to TTBMD based on the formula: TTBMD = 0.9 × BMD-T8-T10 - 2.56. These thresholds (kappa = 0.74) and TTBMD performed well in detecting osteoporosis/osteopenia (kappa = 0.74). Conclusion: Both calculating BMD-T8-T10 threshold (138.0 mg/cm3 for osteopenia and 97 mg/cm3 for osteoporosis) and normalizing BMD-T8-T10 to LBMD demonstrated good performance in identifying osteoporosis in older adults during CT lung cancer screening.

Pancreatic fat infiltration is associated with risk of vertebral fracture in older patients with type 2 diabetes: A longitudinal multicenter study.

AIMS: Patients with type 2diabetesmellitus (T2DM) have high fracture risk. This study explored the associations between pancreatic computed tomography (CT) attenuation, a marker of pancreatic fat, and risk of vertebral fracture in T2DM patients. METHODS: A total of 1486 T2DM patients who aged 50 years and older and without preexisting vertebral fractures during 2019-2023 at our institutions were followed up untilJanuary 2024. CT attenuation of the pancreas, bone and spleen were measured. Pancreatic attenuation/spleen attenuation ratio (P/S) was calculated. Vertebral fractures were evaluated on spine CT images according to Genant's semiquantitative scoring system. RESULTS: A total of 135 cases of vertebral fracture were identified during 26 months of follow-up and 270 patients without vertebral fracture were matched. Pancreatic CT attenuation and the P/S ratio were negatively associated with the risk of vertebral fracture (adjusted hazard ratio (aHR) = 0.97, 95 %confidence interval (CI): 0.96-0.99; aHR = 0.26, 95 %CI: 0.12-0.58). Addition of pancreatic attenuation or P/S ratio improved the performance of bone attenuation-based model (area under the curve = 0.72-0.763 vs 0.63-0.728). CONCLUSION: Pancreatic fat infiltration is an associated factor for vertebral fracture in T2DM patients. Addition of pancreatic fat infiltration improved the predictive performance of the bone-based model.

Brain effect mechanism of lever positioning manipulation on LDH analgesia based on multimodal MRI: a study protocol.

INTRODUCTION: The clinical symptoms of Lumbar Disc Herniation (LDH) can be effectively ameliorated through Lever Positioning Manipulation (LPM), which is closely linked to the brain's pain-regulating mechanisms. Magnetic Resonance Imaging (MRI) offers an objective and visual means to study how the brain orchestrates the characteristics of analgesic effects. From the perspective of multimodal MRI, we applied functional MRI (fMRI) and Magnetic Resonance Spectrum (MRS) techniques to comprehensively evaluate the characteristics of the effects of LPM on the brain region of LDH from the aspects of brain structure, brain function and brain metabolism. This multimodal MRI technique provides a biological basis for the clinical application of LPM in LDH. METHODS AND ANALYSIS: A total of 60 LDH patients and 30 healthy controls, matched by gender, age, and years of education, will be enrolled in this study. The LDH patients will be divided into two groups (Group 1, n = 30; Group 2, n = 30) using a random number table method. Group 1 will receive LPM treatment once every two days, for a total of 12 times over 4 weeks. Group 2 will receive sham LPM treatment during the same period as Group 1. All 30 healthy controls will be divided into Group 3. Multimodal MRI will be performed on Group 1 and Group 2 at three time points (TPs): before LPM (TP1), after one LPM session (TP2), and after a full course of LPM treatment. The healthy controls (Group 3) will not undergo LPM and will be subject to only a single multimodal MRI scan. Participants in both Group 1 and Group 2 will be required to complete clinical questionnaires. These assessments will focus on pain intensity and functional disorders, using the Visual Analog Scale (VAS) and the Japanese Orthopaedic Association (JOA) scoring systems, respectively. DISCUSSION: The purpose of this study is to investigate the multimodal brain response characteristics of LDH patients after treatment with LPM, with the goal of providing a biological basis for clinical applications. TRIAL REGISTRATION NUMBER: https://clinicaltrials.gov/ct2/show/NCT05613179 , identifier: NCT05613179.

Gene association analysis to determine the causal relationship between immune cells and juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a type of chronic childhood arthritis with complex pathogenesis. Immunological studies have shown that JIA is an acquired self-inflammatory disease, involving a variety of immune cells, and it is also affected by genetic and environmental susceptibility. However, the precise causative relationship between the phenotype of immune cells and JIA remains unclear to date. The objective of our study is to approach this inquiry from a genetic perspective, employing a method of genetic association analysis to ascertain the causal relationship between immune phenotypes and the onset of JIA. METHODS: In this study, a two-sample Mendelian randomization (MR) analysis was used to select single nucleotide polymorphisms (SNPs) significantly associated with immune cells as instrumental variables to analyze the bidirectional causal relationship between 731 immune cells and JIA. There were four types of immune features (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)). Finally, the heterogeneity and horizontal reproducibility of the results were verified by sensitivity analysis, which ensured more robust results. RESULTS: We found that CD3 on CM CD8br was causally associated with JIA at the level of 0.05 significant difference (95% CI = 0.630 ~ 0.847, P = 3.33 × 10-5, PFDR = 0.024). At the significance level of 0.20, two immunophenotypes were causally associated with JIA, namely: HLA DR on CD14+ CD16- monocyte (95% CI = 0.633 ~ 0.884, P = 6.83 × 10-4, PFDR = 0.16) and HLA DR on CD14+ monocyte (95% CI = 0.627 ~ 0.882, P = 6.9 × 10-4, PFDR = 0.16). CONCLUSION: Our study assessed the causal effect of immune cells on JIA from a genetic perspective. These findings emphasize the complex and important role of immune cells in the pathogenesis of JIA and lay a foundation for further study of the pathogenesis of JIA.

An insular cortical circuit required for itch sensation and aversion.

Itch encompasses both sensory and emotional dimensions, with the two dimensions reciprocally exacerbating each other. However, whether a shared neural circuit mechanism governs both dimensions remains elusive. Here, we report that the anterior insular cortex (AIC) is activated by both histamine-dependent and -independent itch stimuli. The activation of AIC elicits aversive emotion and exacerbates pruritogen-induced itch sensation and aversion. Mechanistically, AIC excitatory neurons project to the GABAergic neurons in the dorsal bed nucleus of the stria terminalis (dBNST). Manipulating the activity of the AIC → dBNST pathway affects both itch sensation and itch-induced aversion. Our study discovers the shared neural circuit (AIC â†’ dBNST pathway) underlying the itch sensation and aversion, highlights the critical role of the AIC as a central hub for the itch processing, and provides a framework to understand the neural mechanisms underlying the sensation and emotion interaction.

Sexually dimorphic control of affective state processing and empathic behaviors.

Recognizing the affective states of social counterparts and responding appropriately fosters successful social interactions. However, little is known about how the affective states are expressed and perceived and how they influence social decisions. Here, we show that male and female mice emit distinct olfactory cues after experiencing distress. These cues activate distinct neural circuits in the piriform cortex (PiC) and evoke sexually dimorphic empathic behaviors in observers. Specifically, the PiC → PrL pathway is activated in female observers, inducing a social preference for the distressed counterpart. Conversely, the PiC → MeA pathway is activated in male observers, evoking excessive self-grooming behaviors. These pathways originate from non-overlapping PiC neuron populations with distinct gene expression signatures regulated by transcription factors and sex hormones. Our study unveils how internal states of social counterparts are processed through sexually dimorphic mechanisms at the molecular, cellular, and circuit levels and offers insights into the neural mechanisms underpinning sex differences in higher brain functions.

Overexpression of Hippo pathway effector TAZ in tongue squamous cell carcinoma: correlation with clinicopathological features and patients' prognosis.

BACKGROUND: Transcriptional coactivator with PDZ-binding motif (TAZ) is a key downstream effector of Hippo signaling pathway involved in stem cell differentiation and organ development. Recently, its deregulation has been linked to initiation and progression of various cancers. The purpose of this study was to investigate the expression of TAZ in tongue squamous cell carcinoma (TSCC) and its prognostic value in predicting patients' outcomes. METHODS: TAZ expression and localization in a panel of TSCC cell lines and human immortalized oral epithelial cell (HIOEC) were determined by real-time RT-PCR, western blotting, and immunofluorescence. In 52 TSCC tumor specimens with detailed clinical and follow-up data, TAZ abundance was examined by immunohistochemistry and its associations with clinicopathological parameters, Ki-67 expression and patients' survival were further assessed. RESULTS: TAZ mRNA and protein levels were significantly higher in TSCC cells and specimens than those in non-cancerous cells and normal tongue mucosa. Overexpression of TAZ in TSCC was significantly associated with tumor size (P = 0.033), pathological grade (P = 0.026), clinical stage (P = 0.013), Ki-67 expression (P = 0.0485), and reduced overall and disease-free survival (Kaplan-Meier analysis, log-rank test, P = 0.020, 0.019, respectively). Multivariate Cox regression analysis identified TAZ as an important independent predictor for survival of patients with TSCC [HR (hazard ratio), 4.351; 95% CI (95% confidence interval), 1.477-12.819; P = 0.008]. CONCLUSION: Our data indicate that aberrant TAZ overexpression is associated with key clinicopathological features and poor survival in TSCC. These results suggest that TAZ might play critical roles in tumorigenesis of TSCC and become a novel prognostic biomarker and potential therapeutic target for this malignancy.