[Effect analysis of facial nerve decompression surgery in the treatment of Bell's palsy and Hunt syndrome].

Objective:To summarize and analyze the effect of facial nerve decompression surgery for the treatment of Bell's palsy and Hunt syndrome. Methods:The clinical data of 65 patients with facial nerve palsy who underwent facial nerve decompression in our center from October 2015 to October 2022 were retrospectively analyzed, including 54 patients with Bell's palsy and 11 patients with Hunter syndrome. The degree of facial paralysis（HB grade） was evaluated before surgery, and ENoG, pure tone audiometry, temporal bone CT and other examinations were completed. All patients had facial palsy with HB grade V or above after conservative treatment for at least 1 month, and ENoG decreased by more than 90%. All patients underwent facial nerve decompression surgery through the transmastoid approach within 3 months after onset of symptoms. The recovery effect of facial nerve function after surgery in patients with Bell's palsy and Hunter syndrome was summarized and analyzed. In addition, 15 cases in group A（operated within 30-60 days after onset） and 50 cases in group B（operated within 61-90 days after onset） were grouped according to the course of the disease（the interval between onset of symptoms and surgery） to explore the effect of surgical timing on postoperative effect. Results:There was no significant difference between the two groups of patients with Chi-square test（P=0.54） in 42 patients（77.8%, 42/54） with Bell's palsy and 7 patients（63.6%, 7/11） in patients with Hunter syndrome who recovered to grade Ⅰ-Ⅱ. According to the course of the disease, 10 cases（66.7%, 10/15） in group A recovered to grade Ⅰ-Ⅱ after surgery. In group B, 39 patients（78.0%, 39/50） recovered to grade Ⅰ-Ⅱ after surgery, and there was no statistically significant difference between the two groups by Chi-square test（P=0.58）. Conclusion:Patients with Bell's palsy and Hunter syndrome can achieve good results after facial nerve decompression within 3 months of onset, and there is no significant difference in the surgical effect between the two types of patients.

Heterogeneous associations between interleukin-6 receptor variants and phenotypes across ancestries and implications for therapy.

The Phenome-Wide Association Study (PheWAS) is increasingly used to broadly screen for potential treatment effects, e.g., IL6R variant as a proxy for IL6R antagonists. This approach offers an opportunity to address the limited power in clinical trials to study differential treatment effects across patient subgroups. However, limited methods exist to efficiently test for differences across subgroups in the thousands of multiple comparisons generated as part of a PheWAS. In this study, we developed an approach that maximizes the power to test for heterogeneous genotype-phenotype associations and applied this approach to an IL6R PheWAS among individuals of African (AFR) and European (EUR) ancestries. We identified 29 traits with differences in IL6R variant-phenotype associations, including a lower risk of type 2 diabetes in AFR (OR 0.96) vs EUR (OR 1.0, p-value for heterogeneity = 8.5 × 10-3), and higher white blood cell count (p-value for heterogeneity = 8.5 × 10-131). These data suggest a more salutary effect of IL6R blockade for T2D among individuals of AFR vs EUR ancestry and provide data to inform ongoing clinical trials targeting IL6 for an expanding number of conditions. Moreover, the method to test for heterogeneity of associations can be applied broadly to other large-scale genotype-phenotype screens in diverse populations.

Microglial SIX2 suppresses lipopolysaccharide (LPS)-induced neuroinflammation by up-regulating FXYD2 expression.

Parkinson's disease (PD) is a severe neurodegenerative disease associated with the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Although its pathogenesis remains unclear, microglia-mediated neuroinflammation significantly contributes to the development of PD. Here we showed that the sine oculis homeobox (SIX) homologue family transcription factors SIX2 exerted significant effects on neuroinflammation. The SIX2 protein, which is silenced during development, was reactivated in lipopolysaccharide (LPS)-treated microglia. The reactivated SIX2 in microglia mitigated the LPS induced inflammatory effects, and then reduced the toxic effect of conditioned media (CM) of microglia on co-cultured MES23.5 DA cells. Using the LPS-stimulated Cx3cr1-CreERT2 mouse model, we also demonstrated that the highly-expressed SIX2 in microglia obviously attenuated neuroinflammation and protected the DA neurons in SN. Further RNA-Seq analysis on the inflammatory activated microglia revealed that the SIX2 exerted these effects via up-regulating the FXYD domain containing ion transport regulator 2 (FXYD2). Taken together, our study demonstrated that SIX2 was an endogenous anti-inflammatory factor in microglia, and it exerted anti-neuroinflammatory effects by regulating the expression of FXYD2, which provides new ideas for anti-neuroinflammation in PD.

Tibial cortex transverse transport regulates Orai1/STIM1-mediated NO release and improve the migration and proliferation of vessels via increasing osteopontin expression.

Background: Diabetic foot is a major complication of diabetes. The bone transverse transport method could be applied in clinics for treatment, which could improve the metabolism of the tissues via lasting distraction forces. However, the process' specific regulating mechanism is still unknown. Methods: Based on the notion that the healing of bones involves the recruitment of calcium ions, in this study, we established the model of tibial cortex transverse transport (TTT) on rats and then used tissue immunologic detection, such as the double fluorescent staining to explore the expression of the calcium channels' calcium release-activated calcium modulator 1 (Orai1)/stromal interaction molecule 1 (STIM1), which belong to the store-operated calcium entry (SOCE) signaling pathways on the tissues around the bone transport area. By using the laser capture microdissection (LCM) tool, we acquired samples of tissues around the bone and endeavored to identify pivotal protein molecules. Subsequently, we validated the functions of key protein molecules through in vitro and in vivo experiments. Results: After protein profile analysis, we found the differentially expressed key protein osteopontin (OPN). The in vitro experiments verified that, being stimulated by OPN, the migration, proliferation, and angiogenesis of human umbilical vein endothelial cells (HUVEC) were observed to be enhanced. The activation of Orai1/STIM1 might increase the activity of endothelial nitric oxide synthase (eNOS) and its effect on releasing nitric oxide (NO). Subsequently, the migration and proliferation of the HUVECs are improved, which ultimately accelerates wound healing. These signaling pathway was also observed in the OPN-stimulated healing process of the skin wound surface of diabetic mice. Conclusion: This study identifies the molecular biological mechanism of OPN-benefited the migration and proliferation of the HUVECs and provides ideas for searching for new therapeutic targets for drugs that repair diabetes-induced wounds to replace invasive treatment methods. The translational potential of this article: The OPN is highly expressed in the tissues surrounding the TTT bone transfer area, which may possibly stimulate the activation of eNOS to increase NO release through the SOCE pathway mediated by Orai1/STIM1. This mechanism may play a significant role in the angiogenesis of diabetic foot's wounds promoted by TTT, providing new therapeutic strategies for the non-surgical treatment for this disease.

Activation of the YAP/KLF5 transcriptional cascade in renal tubular cells aggravates kidney injury.

The Hippo/YAP pathway plays a critical role in tissue homeostasis. Our previous work demonstrated that renal tubular YAP activation induced by double knockout (dKO) of the upstream Hippo kinases Mst1 and Mst2 promotes tubular injury and renal inflammation under basal conditions. However, the importance of tubular YAP activation remains to be established in injured kidneys in which many other injurious pathways are simultaneously activated. Here, we show that tubular YAP was already activated 6 h after unilateral ureteral obstruction (UUO). Tubular YAP deficiency greatly attenuated tubular cell overproliferation, tubular injury, and renal inflammation induced by UUO or cisplatin. YAP promoted the transcription of the transcription factor KLF5. Consistent with this, the elevated expression of KLF5 and its target genes in Mst1/2 dKO or UUO kidneys was blocked by ablation of Yap in tubular cells. Inhibition of KLF5 prevented tubular cell overproliferation, tubular injury, and renal inflammation in Mst1/2 dKO kidneys. Therefore, our results demonstrate that tubular YAP is a key player in kidney injury. YAP and KLF5 form a transcriptional cascade, where tubular YAP activation induced by kidney injury promotes KLF5 transcription. Activation of this cascade induces tubular cell overproliferation, tubular injury, and renal inflammation.

[Response of Organic Carbon Mineralization to Nitrogen Addition in Micro-aerobic and Anaerobic Layers of Paddy Soil].

In field conditions, a micro-aerobic layer with 1 cm thickness exists on the surface layer of paddy soil owing to the diffusion of dissolved oxygen via flooding water. However, the particularity of carbon and nitrogen transformation in this specific soil layer is not clear. A typical subtropical paddy soil was collected and incubated with13C-labelled rice straw for 100 days. The responses of exogenous fresh organic carbon(13C-rice straw) and original soil organic carbon mineralization to nitrogen fertilizer addition[(NH4)2SO4]in the micro-aerobic layer(0-1 cm) and anaerobic layer(1-5 cm) of paddy soil and their microbial processes were analyzed based on the analysis of 13C incorporation into phospholipid fatty acid(13C-PLFAs). Nitrogen addition promoted the total CO2 and 13C-CO2 emission from paddy soil by 11.4% and 12.3%, respectively. At the end of incubation, with the addition of nitrogen, the total soil organic carbon (SOC) and13C-recovery rate from rice straw in the anaerobic layer were 2.4% and 9.2% lower than those in the corresponding micro-aerobic layer, respectively. At the early stage(5 days), nitrogen addition increased the total microbial PLFAs in the anaerobic layer with a consistent response of bacterial and fungal PLFAs. However, there was no significant effect from nitrogen on microbial abundance in the micro-aerobic layer. Nitrogen addition had no significant impact on the abundance of total 13C-PLFAs in the micro-aerobic and anaerobic layers, but the abundance of 13C-PLFAs for bacteria and fungi in the micro-aerobic layer was decreased dramatically. At the late stage(100 days), the effect of nitrogen addition on microbial PLFAs was consistent with that at the early stage. The abundances of total, bacterial, and fungal 13C-PLFAs were remarkably increased in the anaerobic layer. However, the abundance of 13C-PLFAs in the micro-aerobic layer showed no significant response to nitrogen addition. During the incubation, the content of NH4+-N in the anaerobic soil layer was higher than that in the micro-aerobic soil layer. This indicates that nitrogen addition increased microbial activity in the anaerobic soil layer caused by the higher NH4+-N concentration, as majority of microorganisms preferred to use NH4+-N. Consequently, the microbial utilization and decomposition of organic carbon in the anaerobic soil layer were accelerated. By contrast, richer available N existed in the form of NO3--N in the micro-aerobic soil layer owing to the ammoxidation process. Thus, the shortage of NO3--N preference microorganisms in the paddy soil environment prohibited the microbial metabolism of organic carbon in the micro-aerobic layer. As a whole, nitrogen fertilization enhanced organic carbon loss via microbial mineralization in paddy soil with a weaker effect in the micro-aerobic layer than that in the anaerobic layer, indicating the limited microbial metabolic activity in the surface micro-aerobic layer could protect the organic carbon stabilization in paddy soil. This study emphasizes the heterogeneity of paddy soil and its significant particularity of carbon and nitrogen transformation in micro-aerobic layers. Consequently, this study has implications for optimizing the forms and method for the application of nitrogen fertilizer in paddy cropping systems.

AMPK-Dependent YAP Inhibition Mediates the Protective Effect of Metformin against Obesity-Associated Endothelial Dysfunction and Inflammation.

Hyperglycemia is a crucial risk factor for cardiovascular diseases. Chronic inflammation is a central characteristic of obesity, leading to many of its complications. Recent studies have shown that high glucose activates Yes-associated protein 1 (YAP) by suppressing AMPK activity in breast cancer cells. Metformin is a commonly prescribed anti-diabetic drug best known for its AMPK-activating effect. However, the role of YAP in the vasoprotective effect of metformin in diabetic endothelial cell dysfunction is still unknown. The present study aimed to investigate whether YAP activation plays a role in obesity-associated endothelial dysfunction and inflammation and examine whether the vasoprotective effect of metformin is related to YAP inhibition. Reanalysis of the clinical sequencing data revealed YAP signaling, and the YAP target genes CTGF and CYR61 were upregulated in aortic endothelial cells and retinal fibrovascular membranes from diabetic patients. YAP overexpression impaired endothelium-dependent relaxations (EDRs) in isolated mouse aortas and increased the expression of YAP target genes and inflammatory markers in human umbilical vein endothelial cells (HUVECs). High glucose-activated YAP in HUVECs and aortas was accompanied by increased production of oxygen-reactive species. AMPK inhibition was found to induce YAP activation, resulting in increased JNK activity. Metformin activated AMPK and promoted YAP phosphorylation, ultimately improving EDRs and suppressing the JNK activity. Targeting the AMPK-YAP-JNK axis could become a therapeutic strategy for alleviating vascular dysfunction in obesity and diabetes.

12-inch growth of uniform MoS2 monolayer for integrated circuit manufacture.

Two-dimensional (2D) semiconductors, such as transition metal dichalcogenides, provide an opportunity for beyond-silicon exploration. However, the lab to fab transition of 2D semiconductors is still in its preliminary stages, and it has been challenging to meet manufacturing standards of stability and repeatability. Thus, there is a natural eagerness to grow wafer-level, high-quality films with industrially acceptable scale-cost-performance metrics. Here we report an improved chemical vapour deposition synthesis method in which the controlled release of precursors and substrates predeposited with amorphous Al2O3 ensure the uniform synthesis of monolayer MoS2 as large as 12 inches while also enabling fast and non-toxic growth to reduce manufacturing costs. Transistor arrays were fabricated to further confirm the high quality of the film and its integrated circuit application potential. This work achieves the co-optimization of scale-cost-performance metrics and lays the foundation for advancing the integration of 2D semiconductors in industry-standard pilot lines.

A functional crosstalk between the H3K9 methylation writers and their reader HP1 in safeguarding embryonic stem cell identity.

Histone H3 lysine 9 (H3K9) methylation, as a hallmark of heterochromatin, has a central role in cell lineage and fate determination. Although evidence of a cooperation between H3K9 methylation writers and their readers has started to emerge, their actual interplay remains elusive. Here, we show that loss of H3K9 methylation readers, the Hp1 family, causes reduced expression of H3K9 methyltransferases, and that this subsequently leads to the exit of embryonic stem cells (ESCs) from pluripotency and a reciprocal gain of lineage-specific characteristics. Importantly, the phenotypes of Hp1-null ESCs can be rescued by ectopic expression of Setdb1, Nanog, and Oct4. Furthermore, Setdb1 ablation results in loss of ESC identity, which is accompanied by a reduction in the expression of Hp1 genes. Together, our data support a model in which the safeguarding of ESC identity involves the cooperation between the H3K9 methylation writers and their readers.

Hair and cord blood element levels and their relationship with air pollution, dietary intake, gestational diabetes mellitus, and infant neurodevelopment.

BACKGROUND & AIMS: Exposure to a range of elements, air pollution, and specific dietary components in pregnancy has variously been associated with gestational diabetes mellitus (GDM) risk or infant neurodevelopmental problems. We measured a range of pregnancy exposures in maternal hair and/or infant cord serum and tested their relationship to GDM and infant neurodevelopment. METHODS: A total of 843 pregnant women (GDM = 224, Non-GDM = 619) were selected from the Complex Lipids in Mothers and Babies cohort study. Forty-eight elements in hair and cord serum were quantified using inductively coupled plasma-mass spectrometry analysis. Binary logistic regression was used to estimate the associations between hair element concentrations and GDM risk, while multiple linear regression was performed to analyze the relationship between hair/cord serum elements and air pollutants, diet exposures, and Bayley Scales of infant neurodevelopment at 12 months of age. RESULTS: After adjusting for maternal age, BMI, and primiparity, we observed that fourteen elements in maternal hair were associated with a significantly increased risk of GDM, particularly Ta (OR = 9.49, 95% CI: 6.71, 13.42), Re (OR = 5.21, 95% CI: 3.84, 7.07), and Se (OR = 5.37, 95% CI: 3.48, 8.28). In the adjusted linear regression model, three elements (Rb, Er, and Tm) in maternal hair and infant cord serum were negatively associated with Mental Development Index scores. For dietary exposures, elements were positively associated with noodles (Nb), sweetened beverages (Rb), poultry (Cs), oils and condiments (Ca), and other seafood (Gd). In addition, air pollutants PM2.5 (LUR) and PM10 were negatively associated with Ta and Re in maternal hair. CONCLUSIONS: Our findings highlight the potential influence of maternal element exposure on GDM risk and infant neurodevelopment. We identified links between levels of these elements in both maternal hair and infant cord serum related to air pollutants and dietary factors.

Dephosphorylation of Six2Y129 protects tyrosine hydroxylase-positive cells in SNpc by regulating TEA domain 1 expression.

Parkinson's disease (PD) is a neurodegenerative disease characterized by selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). We recently reported that Six2 could reverse the degeneration of DA neurons in a dephosphorylation state. Here we further identified that Eya1 was the phosphatase of Six2 that could dephosphorylate the tyrosine 129 (Y129) site by forming a complex with Six2 in damaged DA cells. Dephosphorylated Six2 then translocates from the cytoplasm to the nucleus. Using ChIP-qPCR and dual luciferase assay, we found that dephosphorylated Six2 down-regulates TEA domain1 (Tead1) expression, thus inhibiting 6-hydroxydopamine (6-OHDA)-induced apoptosis in DA cells. Furthermore, we showed Six2Y129F/Tead1 signaling could protect against the loss of SNpc tyrosine hydroxylase-positive (TH+) cells and improve motor function in PD model rats. Our results demonstrate a dephosphorylation-dependent mechanism of Six2 that restores the degeneration of DA neurons, which could represent a potential therapeutic target for PD.

Supramolecular Polymer Ion Conductor with Weakened Li Ion Solvation Enables Room Temperature All-Solid-State Lithium Metal Batteries.

Improved durability, enhanced interfacial stability, and room temperature applicability are desirable properties for all-solid-state lithium metal batteries (ASSLMBs), yet these desired properties are rarely achieved simultaneously. Here, in this work, it is noticed that the huge resistance at Li metal/electrolyte interface dominantly impeded the normal cycling of ASSLMBs especially at around room temperature (<30 °C). Accordingly, a supramolecular polymer ion conductor (SPC) with "weak solvation" of Li+ was prepared. Benefiting from the halogen-bonding interaction between the electron-deficient iodine atom (on 1,4-diiodotetrafluorobenzene) and electron-rich oxygen atoms (on ethylene oxide), the O-Li+ coordination was significantly weakened. Therefore, the SPC achieves rapid Li+ transport with high Li+ transference number, and importantly, derives a unique Li2 O-rich SEI with low interfacial resistance on lithium metal surface, therefore enabling stable cycling of ASSLMBs even down to 10 °C. This work is a new exploration of halogen-bonding chemistry in solid polymer electrolyte and highlights the importance of "weak solvation" of Li+ in the solid-state electrolyte for room temperature ASSLMBs.

Effect of indwelling depth of peripheral intravenous catheters on thrombophlebitis.

To clarify the effect of catheter indwelling depth on the occurrence of thrombophlebitis, a total of 339 hospitalized patients were randomly enrolled and divided by the catheter indwelling depth into 2 groups. Then the effect of indwelling depth on thrombophlebitis was analyzed, and the independent influence factors on the occurrence of thrombophlebitis were clarified. There were 49 cases of thrombophlebitis, including 8 tumor-bearing patients and 41 patients with lung infection. Thirteen of the 135 patients with indwelling depth of 1 cm, and 36 of the 204 patients with indwelling depth of 1.9 cm suffered thrombophlebitis. The relationship between incidence rate of thrombophlebitis and clinicopathological parameters was analyzed. It was found the incidence of thrombophlebitis was significantly correlated with males (X2 = 5.77), lung infection (X2 = 7.79), and indwelling depth of 1.9 cm (X2 = 4.223). Multifactor analysis of variance showed the significant independent risk factors of thrombophlebitis were male [hazard ratio (HR) 3.12 (1.39-6.98)], and lung infection (HR 0.22 [0.06-0.69]), and the indwelling depth of 1.9 cm affected the occurrence of thrombophlebitis (HR 0.79 [0.42 -3.09]) but was not an independent risk factor. In our treatment center, while appropriate fixation was ensured, the catheter indwelling depth shall be as short as possible, so as to reduce the occurrence of thrombophlebitis. For patients with lung infection, nursing at the intubation site shall be strengthened, so as to decrease thrombophlebitis.

Surface engineering of Al2O3 nanotubes by ureasolysis method for activating persulfate degradation of antibiotics.

Though ecofriendly, pure Al2O3 has never been used for activation of peroxodisulfate (PDS) to degrade pollutants. We report the fabrication of Al2O3 nanotubes by ureasolysis method for efficient activating PDS degradation of antibiotics. The fast ureasolysis in aqueous AlCl3 solution produces NH4Al(OH)2CO3 nanotubes, which are calcined to porous Al2O3 nanotubes, and the release of ammonia and carbon dioxide engineers the surface features of large surface area, numerous acidic-basic sites and suitable Zeta potentials. The synergy of these features facilitates the adsorption of the typical antibiotics ciprofloxacin and PDS activation, which is proved by experiment results and density functional theory simulation. The proposed Al2O3 nanotubes can catalyze 92-96% degradation of 10 ppm ciprofloxacin within 40 min, with chemical oxygen demand removal of 65-66% in aqueous, and 40-47% in whole including aqueous and catalysts. Ciprofloxacin at high concentration, other fluoroquinolones and tetracycline can also be effectively degraded. These data demonstrate the Al2O3 nanotubes prepared by the nature-inspired ureasolysis method has unique features and great potentials for antibiotics degradation.

Long-term Outcome of Sound Localization with Baha ® Attract System.

BACKGROUND: Spatial hearing is a critical feature in daily life. However, there is quite a range in hearing loss patients regarding the effect of bone conduction device on localization performance. OBJECTIVES: To analyze the localization performance in patients with bilateral conductive or mixed hearing loss fitted with one Baha® Attract system. MATERIALS AND METHODS: This prospective study included 12 patients who had followed up for more than one year. The parameters analyzed included (1) audiological results: sound field threshold, speech discrimination scores (SDSs), and sound localization test, and (2) functional results: scores for the Speech, Spatial and Qualities of Hearing Scale (SSQ) and the Chinese translation of the Spatial Hearing Questionnaire (C-SHQ). RESULTS: The audiological assessments showed a reduction of 28.5 dB in the mean sound field thresholds and improvements of 61.7% in the SDSs for disyllabic words. The root mean square error improved slightly with the Baha® Attract system. Patients showed promising results in the functional questionnaire assessments, with significant improvements in the SSQ and C-SHQ scores. CONCLUSIONS: Although most patients were not able to localize sound accurately after surgery, the change in the scores of the SSQ and C-SHQ indicated that the Baha® Attract system could improve spatial hearing.

Value of the Hyomental Distance Measured With Ultrasound in Forecasting Difficult Laryngoscopy in Newborns.

PURPOSE: Preoperative evaluations of difficult airways are imperative, especially in newborns. The hyomental distance is a reliable index for predicting difficult airways in adults. However, few studies have evaluated the value of the hyomental distance for predicting difficult airways in newborns. It is unclear whether the hyomental distance forecasts a restricted or difficult view when using direct laryngoscopy. We intended to develop an effective system for predicting difficult tracheal intubation in newborns. DESIGN: A prospective observational clinical study. METHODS: Newborns aged 0 to 28 days undergoing oral endotracheal intubation with direct laryngoscopy for elective surgery under general anesthesia were enrolled. The hyomental distance and hyoid level tissue thickness were assessed by ultrasound. Other parameters, such as the mandibular length and sternomental distance, were also evaluated before anesthesia. The glottic structure view under laryngoscopy was graded according to the Cormack-Lehane classification. The patients with Grade 1 and 2 laryngeal views were assigned to Group E. Those with Grade 3 and 4 views were assigned to Group D. FINDINGS: A total of 123 newborns were recruited for our study. The incidence of poor visualization of the larynx during laryngoscopy in our study was 10.6%. The multifactor logistic regression results showed that the hyomental distance was a powerful predictor of difficult laryngoscopy (OR = 0.16, 95% CI 0.03-0.74, P = .019). The curve with the highest sensitivity and specificity and the maximum area under the curve (AUC) was the hyomental distance. The receiver operating characteristic (ROC) curve for the hyomental distance suggested that the best cut-off value was less than equal to 2.74 cm, with an AUC of 0.80 (95% CI 0.64-0.95). CONCLUSIONS: It is noninvasive and feasible to accurately measure the hyomental distance with ultrasound in newborns, and the results are reliable. We believe that the hyomental distance measured with ultrasound could be used as a marker for predicting difficult laryngoscopy in newborns.

[Diagnosis and treatment of rare malignant temporal bone tumors].

Objective:To analyze the diagnosis, treatment and prognosis of patients with rare malignant tumors of the temporal bone. Methods:Four cases of rare temporal bone malignant tumors in our hospital between March 2014 and December 2020 were reviewed, including two cases of chondrosarcoma, one case of fibrosarcoma and one case of endolymphatic cystic papillary adenocarcinoma. There were three males and one female, ages between 28 and 56 years at the time of surgery. Common symptoms included hearing loss, facioplegia, tinnitus, and headache. All patients underwent imaging examinations to evaluate the extent of the lesions. Tumors were removed by subtotal temporal bone resection or infratemporal fossa approach, and postoperative adjuvant radiotherapy was applied if necessary. Results:One of the two chondrosarcoma patients was cured by complete resection of the tumor for 75 months, the other one recurred after the first excision of the tumor and underwent infratemporal fossa approach resection of skull base mass again with no recurrence found yet for 112 months. One patient with fibrosarcoma survived for 28 months after surgery with a positive margin and post-operative radiotherapy. One patient with endolymphatic cystic papillary adenocarcinoma recurred 12 months after subtotal lithotomy, and underwent subtotal temporal bone resection again, combined with radiotherapy. No recurrence was found for 63 months. Conclusion:The incidence of rare temporal bone malignant tumors is extremely low, the location is hidden, and the symptoms are atypical. Attention should be paid for early detection and early treatment. Surgical resection is the main treatment, and radiotherapy can be supplemented in the advanced stage or with a positive margin.

YAP promotes AP-1 expression in tubular epithelial cells in the kidney.

Chronic kidney disease (CKD) is a major health problem. Kidney fibrosis is a hallmark and final common pathway of CKD. The Hippo/yes-associated protein (YAP) pathway regulates organ size, inflammation, and tumorigenesis. Our previous study demonstrated tubular YAP activation by tubule-specific double knockout of mammalian STE20-like protein kinase 1/2 (Mst1/2) induced CKD in mice, but the underlying mechanisms remain to be fully elucidated. Activator protein (AP)-1 activation was found to promote tubular atrophy and tubulointerstitial fibrosis. Therefore, we studied whether YAP regulates AP-1 expression in the kidney. We found that expression of various AP-1 components was induced in kidneys subjected to unilateral ureteric obstruction and in Mst1/2 double knockout kidneys, and these inductions were blocked by deletion of Yap in tubular cells, with Fosl1 being most affected compared with other AP-1 genes. Inhibition of Yap also most highly suppressed Fosl1 expression among AP-1 genes in HK-2 and IMCD3 renal tubular cells. YAP bound to the Fosl1 promoter and promoted Fosl1 promoter-luciferase activity. Our results suggest that YAP controls AP-1 expression and that Fosl1 is the primary target of YAP in renal tubular cells.NEW & NOTEWORTHY Yes-associated protein (YAP) activation leads to tubular injury, renal inflammation, and fibrosis, but the underlying mechanisms are not fully understood. We now provide genetic evidence that YAP promotes activator protein-1 expression and that Fosl1 is the primary target of YAP in renal tubular cells.

Thioridazine protects against disturbed flow-induced atherosclerosis by inhibiting RhoA/YAP-mediated endothelial inflammation.

Atherosclerotic diseases remain the leading cause of adult mortality and impose heavy burdens on health systems globally. Our previous study found that disturbed flow enhanced YAP activity to provoke endothelial activation and atherosclerosis, and targeting YAP alleviated endothelial inflammation and atherogenesis. Therefore, we established a luciferase reporter assay-based drug screening platform to seek out new YAP inhibitors for anti-atherosclerotic treatment. By screening the FDA-approved drug library, we identified that an anti-psychotic drug thioridazine markedly suppressed YAP activity in human endothelial cells. Thioridazine inhibited disturbed flow-induced endothelial inflammatory response in vivo and in vitro. We verified that the anti-inflammatory effects of thioridazine were mediated by inhibition of YAP. Thioridazine regulated YAP activity via restraining RhoA. Moreover, administration of thioridazine attenuated partial carotid ligation- and western diet-induced atherosclerosis in two mouse models. Overall, this work opens up the possibility of repurposing thioridazine for intervention of atherosclerotic diseases. This study also shed light on the underlying mechanisms that thioridazine inhibited endothelial activation and atherogenesis via repression of RhoA-YAP axis. As a new YAP inhibitor, thioridazine might need further investigation and development for the treatment of atherosclerotic diseases in clinical practice.