Early Diagnosis of CNS Virus Infections from Neurological Autoimmune Diseases: A Cross-Sectional Study from China in ER Setting.

It is challenging to differentiate between central nervous system (CNS) virus infections and neurological autoimmune diseases in the emergency department. Considering their different pathogenesis, we assume they differ in neuropsychiatric symptoms and laboratory results. A total of 80 patients were included in this study, 50 with CNS virus infections and 30 with CNS autoimmune diseases, confirmed by a polymerase chain reaction (PCR) of cerebrospinal fluid (CSF). A binary logistic regression model and receiver operating characteristic (ROC) curve were employed to examine the discrimination between the two types of diseases based on neuropsychiatric symptoms and laboratory results. Compared to patients with neurological autoimmune diseases, patients with CNS virus infections had a higher incidence of abnormal behavior (p = 0.026) and abnormal sensation/thought (p = 0.029); higher total (p = 0.005), direct (p = 0.004), and indirect bilirubin (p = 0.004); and increased CSF cell (p = 0.01) and CSF white cell counts (p = 0.01). Patients with disturbance of consciousness and abnormal sensation/thought were 7.79-fold and 5.07-fold more likely to be diagnosed with CNS virus infections (OR = 7.79, p = 0.008; OR = 5.07, p = 0.032). Each unit increase in blood indirect bilirubin concentration and CSF white cell counts increased the risk of developing CNS virus infections by 1.25-fold and 1.01-fold (OR = 1.25, p = 0.016; OR = 1.01, p = 0.011). ROC analysis showed that the area under the curve was 88.0% (p < 0.001). Our study found that patients with CNS viral infections tend to have higher blood indirect bilirubin concentration, CSF leukocyte count, frequency of disorders of consciousness, and abnormal sensation and thought, which may help differentiate them from those with neurological autoimmune diseases.

The Role of Online Well-Being Therapy in Overcoming Allostatic Overload in Medical Workers: A Pilot Randomized Controlled Study.

INTRODUCTION: Stress may lead to allostatic overload. Well-being therapy (WBT) might mitigate it by enhancing psychological well-being and protecting from psychological symptoms. Since no reports are available on the use of WBT in allostatic overload, we evaluated online WBT effects in reducing allostatic overload in medical workers during the coronavirus pandemic. METHODS: Sixty-six participants with allostatic overload were enrolled and randomly assigned to eight sessions of online WBT (n = 32) or eight sessions of an online psychoeducation program on healthy lifestyle (CON) (n = 34). The primary outcome was the prevalence rate of allostatic overload in the two groups at session 8 (T2). Secondary analyses were performed on changes in the PsychoSocial Index (PSI) and Psychological Well-Being (PWB) scales scores at the same time points. Generalized estimating equation models were employed. RESULTS: The WBT group showed a significantly lower rate of allostatic overload at T2 than the CON group (28.13% vs. 70.59%, p < 0.001); similar results were found at T1, T3, and T4 (p < 0.001). Compared to CON, WBT produced a significant decrease in psychological distress (p < 0.001) and abnormal illness behavior (p = 0.031), as well as a significant improvement in PWB autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance (p < 0.001). CONCLUSION: Online WBT may be an effective non-pharmacological therapeutic strategy for individuals with allostatic overload. These findings need to be further validated in different clinical populations.

miR-200b-3p accelerates diabetic wound healing through anti-inflammatory and pro-angiogenic effects.

The poor healing characteristics of diabetic foot ulcers are partially attributed to diabetes-induced pro-inflammatory wounds. Our previous study reported that both miR-146a-5p and miR-200b-3p decrease endothelial inflammation in human aortic endothelial cells and db/db diabetic mice. Although miR-146a-5p has been reported to improve diabetic wound healing, the role of miR-200b-3p is not clear. This study compared the roles of these miRNAs in diabetic wound healing. Two 8-mm full-thickness wounds were created in 12-week-old male db/db mice on the left and right back. After surgery, 100 ng miR-146a-5p, miR-200b-3p, or miR-negative control (NC) was injected in each wound. Full-thickness skin samples were harvested from mice at the 14th day for real-time polymerase chain reaction and immunohistochemistry analyses. At the 14th day, the miR-200b-3p group showed better wound healing and greater granulation tissue thickness than the miR-146a-5p group. The miR-200b-3p group showed a significant decrease of IL-6 and IL-1ß gene expression and a significant increase of Col3α1 gene expression compared to those in the miR-NC group. The miR-200b-3p group had the lowest gene expression of TGF-ß1, followed by the miR-146a-5p and miR-NC groups. Our findings suggest that the miR-200b-3p group had better healing characteristics than the other two groups. Immunohistochemical staining revealed that CD68 immunoreactivity was significantly decreased in both the miR-146a-5p and miR-200b-3p groups compared with that in the miR-NC group. In addition, CD31 immunoreactivity was significantly higher in the miR-200b-3p group than in the miR-146a-5p group. In conclusion, these results suggest that miR-200b-3p is more effective than miR-146a-5p in promoting diabetic wound healing through its anti-inflammatory and pro-angiogenic effects.

A qualitative study on Chinese primary school EFL teachers' beliefs about incorporating intercultural competence into foreign language teaching.

Intercultural competence has become one of the important goals of foreign language education. The potential and value of foreign language education on students' intercultural competence (IC) has been widely recognized by academia. Currently, most of the research on intercultural foreign language teachers in China focuses on university teachers, with little attention paid to primary school EFL teachers. However, the cultivation of IC is a staged and continuous process which cannot be achieved in one stroke. Therefore, it is necessary to include primary school EFL teachers in the study of IC cultivation. This paper presents data on Chinese primary school EFL teachers' beliefs about incorporating IC into foreign language teaching. Specifically, their understanding of culture, IC, and intercultural teaching practices are investigated through interviews. The interview transcriptions were analyzed using thematic analysis. The research found: 1. Chinese primary school EFL teachers generally hold an essentialist view of culture; 2. Teachers emphasize the attitudinal dimension of IC; however, they also exhibit a tendency to oversimplify IC or perceive it as a higher-order skill than language proficiency, hence deeming it unsuitable for cultivation at the primary school level; 3. Most cultural teaching practices are teacher-centered, focusing on background knowledge-style introduction. In general, teachers' intercultural teaching practices align with their cultural outlook. At last, the study explores two suggestions for promoting intercultural foreign language teaching: 1. Supporting primary school EFL teachers in updating their language and culture concepts system; 2. Encouraging teachers to reflect on their daily teaching practices as a major opportunity to promote the development of intercultural foreign language teaching.

Investigating the causal relationship between thyroid dysfunction diseases and osteoporosis: a two-sample Mendelian randomization analysis.

The prevalence of thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) is high. Previous studies have indicated a potential association between TDFDs and OP, yet the causal direction remains unclear. This study aimed to investigate the potential causal relationship between TDFDs and the risk of developing OP and related fractures. We obtained pooled data from genome-wide association studies (GWASs) conducted on TDFDs and OP in European populations and identified single-nucleotide polymorphisms (SNPs) with genome-wide significance levels associated with exposure to TDFDs as instrumental variables. Inverse variance weighted (IVW) was employed as the primary method for Mendelian randomization (MR) analysis, supplemented by MR‒Egger, weighted median, simple mode and weighted mode methods. Sensitivity analyses were conducted to evaluate the robustness of the findings. The IVW method demonstrated an increased risk of OP in patients with TDFDs, including hyperthyroidism and hypothyroidism (TDFDs: OR = 1.11; 95% CI 1.09, 1.13; hypothyroidism: OR = 1.14; 95% CI 1.10, 1.17; hyperthyroidism: OR = 1.09; 95% CI 1.06, 1.12). These findings were supported by supplementary analysis, which revealed a positive correlation between TDFDs and the risk of OP. Multiple sensitivity analyses confirmed the absence of horizontal pleiotropy in the study, thus indicating the robustness of our results. The causal relationship between TDFDs and increased risk of OP implies the need for early bone mineral density (BMD) screening and proactive prevention and treatment strategies for individuals with TDFDs.

FOXS1 acts as an oncogene and induces EMT through FAK/PI3K/AKT pathway by upregulating HILPDA in prostate cancer.

Prostate cancer (PCa) is a widespread global health concern characterized by elevated rates of occurrence, and there is a need for novel therapeutic targets to enhance patient outcomes. FOXS1 is closely linked to different cancers, but its function in PCa is still unknown. The expression of FOXS1, its prognostic role, clinical significance in PCa, and the potential mechanism by which FOXS1 affects PCa progression were investigated through bioinformatics analysis utilizing public data. The levels of FOXS1 and HILPDA were evaluated in clinical PCa samples using various methods, such as western blotting, immunohistochemistry, and qRT-PCR. To examine the function and molecular mechanisms of FOXS1 in PCa, a combination of experimental techniques including CCK-8 assay, flow cytometry, wound-healing assay, Transwell assay, and Co-IP assay were employed. The FOXS1 expression levels were significantly raised in PCa, correlating strongly with tumor aggressiveness and an unfavorable prognosis. Regulating FOXS1 expression, whether upregulating or downregulating it, correspondingly enhanced or inhibited the growth, migration, and invasion capabilities of PCa cells. Mechanistically, we detected a direct interaction between FOXS1 and HILPDA, resulting in the pathway activation of FAK/PI3K/AKT and facilitation EMT in PCa cells. FOXS1 collaborates with HILPDA to initiate EMT, thereby facilitating the PCa progression through the FAK/PI3K/AKT pathway activation.

Brain-wide activation involved in 15 mA transcranial alternating current stimulation in patients with first-episode major depressive disorder.

Background: Although 15 mA transcranial alternating current stimulation (tACS) has a therapeutic effect on depression, the activations of brain structures in humans accounting for this tACS configuration remain largely unknown. Aims: To investigate which intracranial brain structures are engaged in the tACS at 77.5 Hz and 15 mA, delivered via the forehead and the mastoid electrodes in the human brain. Methods: Actual human head models were built using the magnetic resonance imagings of eight outpatient volunteers with drug-naïve, first-episode major depressive disorder and then used to perform the electric field distributions with SimNIBS software. Results: The electric field distributions of the sagittal, coronal and axial planes showed that the bilateral frontal lobes, bilateral temporal lobes, hippocampus, cingulate, hypothalamus, thalamus, amygdala, cerebellum and brainstem were visibly stimulated by the 15 mA tACS procedure. Conclusions: Brain-wide activation, including the cortex, subcortical structures, cerebellum and brainstem, is involved in the 15 mA tACS intervention for first-episode major depressive disorder. Our results indicate that the simultaneous involvement of multiple brain regions is a possible mechanism for its effectiveness in reducing depressive symptoms.

Establishment and validation of nomogram models for overall survival and cancer-specific survival in spindle cell sarcoma patients.

Spindle cell sarcoma (SCS) is rare in clinical practice. The objective of this study was to establish nomograms to predict the OS and CSS prognosis of patients with SCS based on the Surveillance, Epidemiology, and End Results (SEER) database. The data of patients with SCS between 2004 and 2020 were extracted from the SEER database and randomly allocated to a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were used to screen for independent risk factors for both overall survival (OS) and cancer-specific survival (CSS). Nomograms for OS and CSS were established for patients with SCS based on the results of multivariate Cox analysis. Then, we validated the nomograms by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Finally, Kaplan‒Meier curves and log-rank tests were applied to compare patients with SCS at three different levels and in different treatment groups. A total of 1369 patients with SCS were included and randomly allocated to a training cohort (n = 1008, 70%) and a validation cohort (n = 430, 30%). Age, stage, grade, tumour location, surgery, radiation and diagnosis year were found to be independent prognostic factors for OS by Cox regression analysis, while age, stage, grade, tumour location and surgery were found to be independent prognostic factors for CSS. The nomogram models were established based on the results of multivariate Cox analysis for both OS and CSS. The C-indices of the OS model were 0.76 and 0.77 in the training and validation groups, respectively, while they were 0.76 and 0.78 for CSS, respectively. For OS, the 3- and 5-year AUCs were 0.801 and 0.798, respectively, in the training cohort and 0.827 and 0.799, respectively, in the validation cohort; for CSS, they were 0.809 and 0.786, respectively, in the training cohort and 0.831 and 0.801, respectively, in the validation cohort. Calibration curves revealed high consistency in both OS and CSS between the observed survival and the predicted survival. In addition, DCA was used to analyse the clinical practicality of the OS and CSS nomogram models and revealed that they had good net benefits. Surgery remains the main treatment method for SCS patients. The two nomograms we established are expected to accurately predict the personalized prognosis of SCS patients and may be useful for clinical decision-making.

Evaluation of measurement accuracy of wearable devices for heart rate variability.

This paper proposed a method based on heart rate variability (HRV) for evaluating the accuracy of wearable devices in measuring heart rate. HRV refers to the variation in time intervals between successive heartbeats, widely used in many fields such as clinical and sports fields. Wearable devices such as Electrocardiogram (ECG) electrode patches have gained popularity due to their portability and ease of use. However, they can be prone to measurement interference caused by environmental noise, human respiration, etc. The proposed method consists of four main components: selection of "gold standard measurement devices", identification of HRV measurement metrics, construction of an HRV evaluation framework, and quantification of measurement errors. The method is validated through simulated experiments using ECG patches. The evaluation framework and quantification model established in this method have significant implications in establishment of industry standards and diagnosis of diseases in clinical practice.

Evidence of a large current of transcranial alternating current stimulation directly to deep brain regions.

Deep brain regions such as hippocampus, insula, and amygdala are involved in neuropsychiatric disorders, including chronic insomnia and depression. Our recent reports showed that transcranial alternating current stimulation (tACS) with a current of 15 mA and a frequency of 77.5 Hz, delivered through a montage of the forehead and both mastoids was safe and effective in intervening chronic insomnia and depression over 8 weeks. However, there is no physical evidence to support whether a large alternating current of 15 mA in tACS can send electrical currents to deep brain tissue in awake humans. Here, we directly recorded local field potentials (LFPs) in the hippocampus, insula and amygdala at different current strengths (1 to 15 mA) in 11 adult patients with drug-resistant epilepsy implanted with stereoelectroencephalography (SEEG) electrodes who received tACS at 77.5 Hz from 1 mA to 15 mA at 77.5 Hz for five minutes at each current for a total of 40 min. For the current of 15 mA at 77.5 Hz, additional 55 min were applied to add up a total of 60 min. Linear regression analysis revealed that the average LFPs for the remaining contacts on both sides of the hippocampus, insula, and amygdala of each patient were statistically associated with the given currents in each patient (p < 0.05-0.01), except for the left insula of one subject (p = 0.053). Alternating currents greater than 7 mA were required to produce significant differences in LFPs in the three brain regions compared to LFPs at 0 mA (p < 0.05). The differences remained significant after adjusting for multiple comparisons (p < 0.05). Our study provides direct evidence that the specific tACS procedures are capable of delivering electrical currents to deep brain tissues, opening a realistic avenue for modulating or treating neuropsychiatric disorders associated with hippocampus, insula, and amygdala.

Candida parapsilosis-Caused Arthritis with Rice Body Formation: A Case Presentation and Literature Review.

A 68-year-old male patient came to the orthopedics department because of swelling and pain in his left shoulder joint. He received more than 15 intraarticular steroid injections in the shoulder joint at a local private hospital. MRI showed that the synovial membrane of the joint capsule was thickened and swollen, and there were extensive "rice body-like" low T2 signal shadows filling. Arthroscopic removal of rice bodies and subtotal bursectomy were performed. The observation channel was placed through the posterior approach, and a large amount of rice bodies in yellow bursa fluid were observed to flow out. Rice bodies with a diameter of approximately 1-5 mm filled the joint cavity were seen in the observation channel. The histopathological examination of the rice body showed that it was mainly composed of fibrin without a clear tissue structure. Bacterial and fungal cultures of synovial fluid suggested Candida parapsilosis infection, so the patient received antifungal treatment. However, the shoulder swelled again after three weeks, MRI revealed that there was significant fluid accumulation in the subacromial-subdeltoid region with necrotic synovial tissue floating and ultrasound examination showed joint cavity effusion, synovial hyperplasia, and some synovium looked like "floating weeds". After 2 weeks, there were recurrent rice bodies in the articular cavity. Arthroscopic surgery was performed again to clean the joint and a catheter was placed for irrigation and drainage, and a large amount of necrotic synovial tissue floating as seen in ultrasound. Finally, patient received sensitive antifungal treatment and did not relapse within 6 months. During the recurrence in the current case, we recorded the process of rice body formation, which has for the first time been reported.

A mixed method study on Chinese primary school EFL teachers' preparation, affecting factors and support needed to implement intercultural foreign language teaching.

Cultivating intercultural competence is a long-term and staged process requiring the efforts of all counterparts in the education field from primary school up to university. Currently, most research on intercultural education in China focuses on the tertiary education context, and little attention has been paid to elementary education as well as primary school EFL teachers. Against this background, this study intends to investigate Chinese primary school EFL teachers' preparedness for intercultural foreign language teaching (IFLT), its influencing factors, and the support teachers need to implement IFLT. A convergent mixed method was used in this study. Data was collected through questionnaires and interviews, SPSS and the thematic analysis method were used to analyze the data. Via both quantitative and qualitative methods, this empirical study found that: 1. Primary school EFL teachers are not well prepared for IFLT; 2. Textbooks, the current evaluation system, teachers' lack of literacy in intercultural competence, insufficient teacher training on intercultural competence, and teachers' lack of time and energy are five major factors that constrain the implementation of IFLT; 3. Support from school administration, the construction of intercultural-related materials and resources, and practice-oriented teacher training are the three main support teachers need. Based on these findings, the role of textbooks, experience abroad and general materials on culture in promoting IFLT were discussed. At last, implications and future research directions were proposed.

Temporal and spatial assembly of inner ear hair cell ankle link condensate through phase separation.

Stereocilia are actin-based cell protrusions of inner ear hair cells and are indispensable for mechanotransduction. Ankle links connect the ankle region of developing stereocilia, playing an essential role in stereocilia development. WHRN, PDZD7, ADGRV1 and USH2A have been identified to form the so-called ankle link complex (ALC); however, the detailed mechanism underlying the temporal emergence and degeneration of ankle links remains elusive. Here we show that WHRN and PDZD7 orchestrate ADGRV1 and USH2A to assemble the ALC through liquid-liquid phase separation (LLPS). Disruption of the ALC multivalency for LLPS largely abolishes the distribution of WHRN at the ankle region of stereocilia. Interestingly, high concentration of ADGRV1 inhibits LLPS, providing a potential mechanism for ALC disassembly. Moreover, certain deafness mutations of ALC genes weaken the multivalent interactions of ALC and impair LLPS. In conclusion, our study demonstrates that LLPS mediates ALC formation, providing essential clues for understanding the pathogenesis of deafness.

Clinical Efficacy of Intra-Articular Injection with P-PRP Versus that of L-PRP in Treating Knee Cartilage Lesion: A Randomized Controlled Trial.

OBJECTIVE: Platelet-rich plasma（PRP), with different concentration of leukocytes, may lead to varying effects in the treatment of cartilage lesions. So far, current research has not shown enough evidence on this. To evaluate the clinical efficacy and safety of intra-articular injection with pure platelet-rich plasma (P-PRP) versus those of leukocyte platelet-rich plasma (L-PRP) in treating knee cartilage lesions, we conducted a double-blind, randomized controlled clinical trial with a larger sample and longer follow-up period. METHODS: From October 2019 to October 2020, 95 patients were invited to participate in our study, and 60 (63.2%) were randomized to P-PRP (n = 30) or L-PRP (n = 30) groups. Patients from the two groups were treated with knee intra-articular injections of P-PRP or L-PRP. Visual analog scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were assessed using an unpaired t-test for independent samples preoperatively and at 6 weeks, 12 weeks, 6 months, and 12 months after intervention. RESULTS: We followed up 27 cases in the P-PRP group and 26 cases in the L-PRP group. No significant differences in VAS and WOMAC scores were found between the two groups before the intervention (p > 0.05). The WOMAC Pain and VAS-Motions scores of the P-PRP group were significantly lower than those of the L-PRP group at 6 weeks after the intervention (p < 0.05). While the long-term clinical efficacy of both injections was similar and weakened after 12 months, more adverse events were found in the L-PRP group. CONCLUSIONS: The short-term results demonstrate a positive effect in reducing pain and improving function in patients with knee cartilage lesions in the two groups. While the P-PRP injection showed better clinical efficacy in the early phase of postoperative rehabilitation and resulted in fewer adverse events, long-term follow-up showed similar and weakened efficacy after 12 months. TRIAL REGISTRATION: ChiCTR1900026365. Registered on October 3, 2019, http://www.chictr.org.cn/showproj.aspx?proj=43911.

Identify Potential Urine Biomarkers for Bladder Cancer Prognosis Using NGS Data Analysis and Experimental Validation.

Bladder cancer (BC) is one of the most often reported malignancies globally, with a high recurrence rate and associated morbidity and mortality, especially in advanced BC. There has been a surge in the number of molecular targets revealed for BC prognosis and treatment. However, there is still a great need to discover novel biomarkers. Consequently, the current study investigated biomarkers that might indicate the progression of bladder cancer. In this study, bioinformatics analysis was done on a single GEO dataset, and TCGA-BLCA information was connected with differentially expressed genes (DEGs). The levels of mRNA and protein expression were validated using qRT-PCR. According to our findings, CRYAB, ECM1, ALDOB, AOC, GPX3, IGFBP7, AQP2, LASS2, TMEM176A, GALNT1, and LASS2 were highly enriched in cell division, identical protein binding, and developmental process in bladder cancer patients. In addition, among the highly differentiated genes, ECM1, GALNT1, LASS2, and GPX3 showed significant molecular alterations in BC, which are crucial for marker identification. Moreover, the mRNA, CNVs, and protein levels of ECM1, GALNT1, LASS2, and GPX3 were significantly increased in BC patients. Our predictions and analysis studies stated that these four genes act as urine biomarkers and played a crucial role in disease prognosis and the therapeutic process of bladder cancer. Our outcomes showed that these four novel urine biomarkers have the potential to provide innovative diagnostics, early predictions, and disease targets, ultimately improving the BC patient's prognosis.

CDX2 as a Predictive Biomarker Involved in Immunotherapy Response Suppresses Metastasis through EMT in Colorectal Cancer.

Background: Studies have confirmed that Caudal Type Homeobox 2 (CDX2) plays a tumor suppressor role in colorectal cancer (CRC) and as a prognostic and predictive marker for colorectal cancer. The epithelial to mesenchymal transition (EMT) is a transdifferentiation process, providing migratory and invasive properties to cancer cells during tumor progression. However, the role of CDX2 during the activation of EMT in CRC maintains controversial. Aim: To investigate whether CDX2 is associated with EMT in CRC. Methods: Forty-six CRC patients were included in the study. Expressions of CDX2, E-cadherin, and N-cadherin in all CRC patients were detected by IHC. ROC assays were applied to detect cut-off points for IHC scores to distinguish high and low expressions of CDX2 in 46 CRC samples. The prognostic value of CDX2 was statistically analyzed. MTT, Western blot, invasion, and migration assays in vitro were employed to explore the function of CDX2. Results: We observed that high expressions of CDX2 and E-cadherin as well as low expressions of N-cadherin were significantly correlated with favorable prognosis. The levels of CDX2 protein exhibited a positive associated with E-cadherin while negative correlation with N-cadherin. Then, the low expression of CDX2 and high expression of CA199 in combination are positively related with poor prognosis. Overexpression of CDX2 reduced expression of MMP-2 and diminished cell proliferation, invasion, and migration, while knockdown CDX2 enhanced MMP-2 expression and increased cell proliferation, invasion, and migration in HCT-116 cells. CDX2 was correlated with expression of EMT markers. Overexpression of CDX2 suppressed the EMT markers indicating that CDX2 suppresses CRC cell viability, invasion, and metastasis through inhibiting EMT. Finally, we found that the expression of CDX2 was negatively associated with Th1 cells, macrophages, Th2 cells, cytotoxic cells, T cells, and T helper cells. Conclusions: These results indicated CDX2 as prognostic biomarkers involved in immunotherapy response for CRC. CDX2 loss promotes metastasis in CRC through a CDX2-dependent mechanism.

Values of OAS gene family in the expression signature, immune cell infiltration and prognosis of human bladder cancer.

BACKGROUND: Bladder cancer (BLCA) is one of the most common genitourinary malignancies in the world, but its pathogenic genes have not been fully identified and the treatment outcomes are still unsatisfactory. Although the members of 2', 5'-oligoadenylate synthetase (OAS) gene family are known involved in some tumorous biological processes, the roles of the OAS gene family in BLCA are still undetermined. METHODS: By combining vast bioinformatic datasets analyses of BLCA and the experimental verification on clinical BLCA specimen, we identified the expressions and biological functions of OAS gene family members in BLCA with comparison to normal bladder tissues. RESULTS: The expression levels of OAS gene family members were higher in BLCA than in normal bladder tissues. The expression levels of most OAS genes had correlations with genomic mutation and methylation, and with the infiltration levels of CD4 + T cells, CD8 + T cells, neutrophils, and dendritic cells in the microenvironment of BLCA. In addition, high expressions of OAS1, OAS2, OAS3, and OASL predicted better overall survival in BLCA patients. CONCLUSIONS: The highly expressed OAS genes in BLCA can reflect immune cells infiltration in the tumor microenvironment and predict the better overall survival of BLCA, and thus may be considered as a signature of BLCA. The study provides new insights into the diagnosis, treatment, and prognosis of BLCA.

Deafness-related protein PDZD7 forms complex with the C-terminal tail of FCHSD2.

In cochlea, deafness-related protein PDZD7 is an indispensable component of the ankle link complex, which is critical for the maturation of inner-ear hair cell for sound perception. Ankle links, connecting the different rows of cochlear stereocilia, are essential for the staircase-like development of stereocilia. However, the molecular mechanism of how PDZD7 governs stereociliary development remains unknown. Here, we reported a novel PDZD7-binding partner, FCHSD2, identified by yeast two-hybrid screening. FCHSD2 was reported to be expressed in hair cell, where it co-operated with CDC42 and N-WASP to regulate the formation of cell protrusion. The association between FCHSD2 and PDZD7 was further confirmed in COS-7 cells. More importantly, we solved the complex structure of FCHSD2 tail with PDZD7 PDZ3 domain at 2.0 Šresolution. The crystal structure shows that PDZD7 PDZ3 adopts a typical PDZ domain topology, comprising five ß strands and two α helixes. The PDZ-binding motif of FCHSD2 tail stretches through the αB/ßB groove of PDZD7 PDZ3. Our study not only uncovers the interaction between FCHSD2 tail and PDZD7 PDZ3 at the atomic level, but also provides clues of connecting the ankle link complex with cytoskeleton dynamics for exploiting the molecular mechanism of stereociliary development.