Inhibition of CDK9 exhibits anticancer activity in hepatocellular carcinoma cells via targeting ribonucleotide reductase.

Cyclin-dependent kinase 9 (CDK9) inhibitors are a novel category of anticancer treatment for cancers. However, their effects on hepatocellular carcinoma (HCC) are rarely investigated. Human ribonucleotide reductase (RR, which consists of RRM1 and RRM2 subunits) catalyzes the conversion of ribonucleoside diphosphate into 2'-deoxyribonucleoside diphosphate to maintain the homeostasis of nucleotide pools, which play essential roles in DNA synthesis and DNA repair. In this study, we identified that CDK9 protein expression in adjacent non-tumor tissues predicted HCC patients' overall and progression-free survivals. The anticancer activity of a CDK9-selective inhibitor, LDC000067, on HCC cells was positively associated with its ability to inhibit the expression of RRM1 and RRM2. LDC000067 downregulated RRM1 and RRM2 expression through post-transcriptional pathway. Specifically, LDC000067 triggered RRM2 protein degradation via multiple pathways, including proteasome-, lysosome-, and calcium-dependent pathways. Furthermore, CDK9 positively correlates with RRM1 or RRM2 expression in HCC patients, and the expressions of these three genes were associated with the higher infiltration of immune cells in HCC. Taken together, this study identified the prognostic relevance of CDK9 in HCC and the molecular mechanism for the anticancer effect of CDK9 inhibitors on HCC.

Anlotinib dramatically improved pulmonary hypertension and hypoxia caused by Pulmonary Tumor Thrombotic Microangiopathy (PTTM) associated with gastric carcinoma: a case report.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, demonstrating rapid progression of pulmonary hypertension (PH) and respiratory failure. Although a number of treatments have been attempted for patients diagnosed with or suspected of having PTTM, successful-treated cases of PTTM were mainly from imatinib therapy, which was a PDGF receptor inhibitor. Anlotinib was a novel tyrosine kinase inhibitor that targets VEGFR, FGFR, PDGFR, and c-kit. CASE PRESENTATION: We reported a patient of PTTM associated with gastric carcinoma, whom were treated with anlotinib, thereby exhibiting significant improvement of PH and respiratory dysfunction. CONCLUSION: Our case provides a new understanding of therapy to PTTM, with implications for defining anlotinib as candidate drug for PTTM. Clinical diagnosis and prompt initiation of anlotinib might be one of the strategies in patients with unstable PTTM.

Identification and analysis of anti-tumor effective substances in Yangzheng Mixture.

Yangzheng Mixture is a traditional Chinese medicine used in clinical practice as an adjuvant therapy for tumors. However, little is known about its active components in tumor treatment. The purpose of this study was to explore the potential anti-tumor components of Yangzheng Mixture to better promote its clinical application. Using LC-MS/MS, 43 components were detected in concentrated Yangzheng Mixture. Six components, comprising astragaloside, calycosin, formononetin, isoquercitrin, ononin, and calycosin-7-O-ß-D-glucoside, were identified in rat plasma. The cancer cell absorption assay showed that the intracellular concentration of four components, calycosin, calycosin-7-O-ß-D-glucoside, formononetin, and ononin, increased with extended incubation time and demonstrated potential anti-tumor effects. The MTT assay results confirmed that Yangzheng Mixture inhibited different tumor cells proliferation. Additionally, the colony formation assay, flow cytometry analysis and wound healing displayed that Yangzheng Mixture and a combination of four components could inhibit colony formation, arrest the cell cycle and impair cell migration of tumor cells, including HCT-116, MHCC-97L, MCF-7 and NCI-H1299. In summary, our study highlighted the plausible application of Yangzheng Mixture as a potential adjuvant treatment for tumors. Furthermore, it identified effective anti-tumor components and provided evidences for the further clinical application of Yangzheng Mixture.

Piezosurgery versus conventional osteotomy: a randomized clinical trial on pain and anxiety in children with unerupted mandibular third molars.

OBJECTIVE: Dental anxiety for unerupted mandibular third molars extraction in children under local anesthesia is a tricky problem. The purpose of this study was to compare psychological and physiologic findings of extractions of unerupted mandibular third molars in children by piezosurgery and conventional osteotomy. MATERIALS AND METHODS: This prospective, single-center, double-blind study included children who required extraction of mandibular third molars under local anesthesia. All subjects were randomly divided into two groups: piezosurgery and conventional osteotomy (control). The primary outcome variables were dental anxiety assessed by the Modified Child Fear Survey Schedule Dental Subscale (CFSS-DS) and postoperative pain qualified by the visual analog scale (VAS). Secondary outcome variables included blood pressure, heart rate, saturation, and operation duration. The data were analyzed by t-test and chi-square test (P ≤ 0.05). RESULTS: All 40 study patients (37.5% males and 62.5% females with an average age of 14.43 ± 1.32 years) completed the entire trial. There were no statistically significant differences observed between the two groups in terms of gender allocation, age, side of extraction, and Winter's Classification (P > 0.05). The operation duration of the piezosurgery group was significantly longer than the conventional osteotomy group (P < 0.01). The VAS scores showed that pain levels of children in the piezosurgery group were significantly less than the conventional osteotomy group on the first and third days postoperatively (P < 0.05 and P < 0.01, respectively). The CFSS-DS score in the piezosurgery group significantly decreased compared to the conventional osteotomy group (P < 0.05). Compared with the conventional osteotomy group, a significant decrease in heart rate, and lower systolic and diastolic blood pressures were observed after extraction in the piezosurgery group (P < 0.05 and P < 0.01, respectively). CONCLUSION: Compared with conventional osteotomy, piezosurgery can effectively reduce postoperative pain and have some effect in relieving dental anxiety for the extraction of unerupted mandibular third molars in children. CLINICAL RELEVANCE: Piezosurgery may be a viable technique for the extraction of unerupted mandibular third molars in children under local anesthesia.

Assessment of condylar positional changes in severe skeletal class II malocclusion after surgical-orthodontic treatment.

OBJECTIVES: This study aimed to determine the positional changes in the condyle in the temporomandibular joint (TMJ) of severe skeletal class II malocclusion patients treated with surgical-orthodontics. MATERIALS AND METHODS: The measurements of TMJ space in 97 severe skeletal class II malocclusion patients (20 males, 77 females, mean age, 24.8 years, mean ANB = 7.41°) were assessed using limited cone-beam computed tomography (LCBCT) images acquired before orthodontics (T0) and 12 months after surgery (T1). 3D remodeling of the TMJ and measurements of the anterior space (AS), superior space (SS), and posterior space (PS) were performed to determine the position of the condyle for each joint. All data were analyzed by t test, correlation analysis, and Pearson correlation coefficient. RESULTS: The mean AS, SS, and PS values after the therapy changed from 1.684 to 1.680 mm (0.24%), 3.086 to 2.748 mm (10.968%), and 2.873 to 2.155 mm (24.985%), respectively. The decreases in SS and PS were statistically significant. Positive correlations were found in the mean AS, SS, and PS values between the right and left sides. CONCLUSIONS: The combination of orthodontic and surgical treatment makes the condyle move counterclockwise in the TMJ in severe skeletal class II patients. CLINICAL RELEVANCE: Studies of temporomandibular joint (TMJ) intervals changes in patients with severe skeletal class II after sagittal split ramus osteotomy (SSRO) are limited. The postoperative joint remodeling, resorption, and related complications remain unstudied.

Evaluation of carotid plaque vulnerability with different echoes by shear wave elastography and CEUS.

OBJECTIVE: Using shear wave elastography (SWE) and contrast enhanced ultrasound (CEUS)to examine carotid plaques with different echoes, and explore a reliable method to quantify characteristics associated with vulnerable carotid plaques. METHODS: 2D ultrasound, SWE and CEUS were performed on 244 carotid plaques, and the echoes were evaluated according to the Gray-Weale classification scale and gray-scale median (GSM), and the mean Young's modulus (YM) of the plaque was measured and the intraplaque neovascularization was observed to investigate the relationship between carotid plaque types with different echo characteristics, GSM and the values of each parameter of YM and CEUS. The relationship between GSM and YM and CEUS values was investigated. RESULTS: The differences between GSM values (F = 49.742, P < 0.001), with the maximum, mean, and minimum YM values of ultrasound elastography (P < 0.001), and with the number (P < 0.001) and density (P = 0.047) of neovascularization on CEUS were statistically significant for the different echogenic types of plaques, and the lower the echogenicity of the plaque, the lower the GSM values (r = 0.632, P < 0.001), the smaller the YM values (all r > 0, P < 0.001), and the higher the neovascularization number and density values (r < 0, P < 0.001); and there were also statistically significant differences between the above indicators in the vulnerable and stable plaque groups (all P < 0.05). CONCLUSION: GSM, SWE, and CEUS techniques can quantitatively evaluate the vulnerability of different echo carotid plaques in a more comprehensive and objective manner, which may help clinical identification of vulnerable plaques, and provide important reference values for early diagnosis and treatment in clinical practice.

Enhanced photothermoelectric detection in Co:BiCuSeO crystals with tunable Seebeck effect.

BiCuSeO is a widely-used thermoelectric material recently proved to be an appealing candidate for broadband photothermoelectric (PTE) detection. Developing a simple and scalable route for advancing PTE properties is therefore essential to explore the full potential of BiCuSeO. Here we systematically demonstrated that Co3+ atomic doping strategies in BiCuSeO single crystals (Co concentration of 1%, 2% and 4%) could modulate the Seebeck coefficient and thus strongly improve the performance of BiCuSeO PTE photodetectors across visible to infrared spectral regions. Benefiting from these strategies, a large enhancement on photovoltage responsivity is achieved and the response time of a 4% Co:BiCuSeO PTE photodetector is one order of magnitude faster than those in most of PTE photodetectors. Also, Co:BiCuSeO PTE photodetectors show good stability with changeless photoresponse after being exposed to air for three months. Therefore, the controllable atomic doping of BiCuSeO with tunable PTE properties as well as fast and broadband photodetection provides the feasibility for facilitating ongoing research toward PTE devices.

Piezosurgery Versus Conventional Osteotomy: A Comparison of Techniques in the Extraction of Unerupted Mandibular Third Molars in Children.

PURPOSE: Piezoelectric bone surgery is a precise and effective osteotomy technique used in maxillofacial surgery. The purpose of this study was to compare postoperative sequelae and efficacy of extractions of unerupted mandibular third molars in children by piezosurgery and conventional osteotomy. METHODS: Healthy subjects, aged 10 to 14 years, needing removal of their bilateral lower third molars were included in this study. The right or left unerupted mandibular third molars were randomly extracted by either piezosurgery or conventional osteotomy. Pain (qualified by the visual analog scale), facial swelling, trismus, and operation duration were evaluated. RESULTS: All 32 study patients (40.6% males and 59.4% females with an average age of 11.91 ± 1.40 years) completed the entire trial. Swelling and trismus experienced by the conventional osteotomy were more severe than the piezosurgery group on the third (10.34 ± 2.36 mm vs 4.9 ± 1.95 mm and 6.09 ± 2.08 mm vs 2.34 ± 1.79 mm, respectively) and seventh (2.03 ± 1.26 mm vs 0.25 ± 0.57 mm and 0.91 ± 1.00 mm vs 0.09 ± 0.30 mm, respectively) days postoperatively (P < .01). Visual analog scale showed that pain levels of children in the piezosurgery group were significantly less than the conventional osteotomy group on third day postoperatively (2.06 ± 1.41 vs 4.81 ± 1.94; P < .01). The operation duration of the piezosurgery group was significantly longer than the conventional osteotomy group (27.16 ± 5.75 minutes vs 16.69 ± 3.22 minutes; P < .01). CONCLUSION: Compared with conventional osteotomy, piezosurgery can effectively reduce the severity of postoperative sequelae for the extraction of unerupted lower third molars in children.

Adenovirus diseases: a systematic review and meta-analysis of 228 case reports.

OBJECTIVE: The clinical characteristics of various adenovirus (ADV) infection are underexplored up till now. To investigate the risk factors, manifestation, current status of ADV species, treatment and prognosis of this disease. METHODS: We performed a Pubmed and Embase systematic review for case report reporting the ADV infection to analyze the clinical characteristics of disease. RESULTS: Initial database searched identified articles of which 168 (228 cases) were included in the final analysis. Previous solid organ transplantation [odds ratio (OR) = 3.45, 95% CI 1.31-9.08, P = 0.01], hematopoietic stem cell transplant (OR = 4.24, 95% CI 1.33-13.51, P = 0.01) and hematological malignancy (OR = 4.78, 95% CI 1.70-13.46, P = 0.01) were associated with increased risk of disseminated ADV infection. Use of corticosteroids (OR = 3.86, 95% CI 1.21-12.24, P = 0.02) was a significant risk factor for acquiring urinary tract infections. A total of six species (21 types) of ADV infection have been identified in 100/228 (43.9%) cases. ADV B was the most common species. ADV B species (26/60, 52.0% or 5/41, 12.2% P = 0.001) were more isolated in patients with ADV pneumonia. ADV C (13/15, 86.7% versus 35/86, 40.7% P = 0.001) species were more identified in patients with disseminated disease. The species associated with keratoconjunctivitis is only ADV D in our analysis. Urinary tract ADV infections were observed in ADV A/B/D species. Cidofovir (CDV) (82/228, 36.0%) remained the most commonly antiviral therapy in our cases, followed by ribavirin (15/228, 6.6%), ganciclovir (18/228, 7.9%), and brincidofovir (12/228, 5.3%). Brincidofovir was administered as salvage therapy in 10 cases. Death was reported in 81/228 (35.5%) patients. Mortality rate was higher among patients with gastrointestinal (GI) ADV infection (5/10, 50.0%), ADV pneumonia (20/45, 44.4%) and disseminated ADV infection (53/122, 43.4%). CONCLUSION: Previous solid organ transplantation, hematopoietic stem cell transplant and hematological malignancy were risk factors for disseminated ADV infection. Use of corticosteroids was significant for urinary tract ADV infection. Different species correlated with different clinical manifestations of infection. Mortality rate was higher among patients with GI disease, pneumonia and disseminated disease. Our review clarified the current treatment of ADV infections, and more treatment required further investigation.

Clinical features of cryptococcosis in patients with different immune statuses: a multicenter study in Jiangsu Province-China.

BACKGROUND: Current guidelines support different management of cryptococcosis between severely immunodeficient and immunocompetent populations. However, few studies have focused on cryptococcosis patients with mild-to-moderate immunodeficiency. We performed this study to determine the clinical features of pulmonary (PC) and extrapulmonary cryptococcosis (EPC) and compared them among populations with different immune statuses to support appropriate clinical management of this public health threat. METHODS: All cases were reported by 14 tertiary teaching hospitals in Jiangsu Province, China from January 2013 to December 2018. The trends in incidence, demographic data, medical history, clinical symptoms, laboratory test indicators, imaging characteristics and diagnostic method of these patients were then stratified by immune status, namely immunocompetent (IC, patients with no recognized underlying disease or those with an underlying disease that does not influence immunity, such as hypertension), mild-to-moderate immunodeficiency (MID, patients with diabetes mellitus, end-stage liver or kidney disease, autoimmune diseases treated with low-dose glucocorticoid therapy, and cancer treated with chemotherapy) and severe immunodeficiency (SID, patients with acquired immunodeficiency syndrome, haematologic malignancies, solid organ transplantation or haematologic stem cell transplantation, idiopathic CD4 lymphocytosis, agranulocytosis, aggressive glucocorticoid or immunosuppressive therapy and other conditions or treatments that result in severe immunosuppression). RESULTS: The clinical data of 255 cryptococcosis patients were collected. In total, 66.3% of patients (169) were IC, 16.9% (43) had MID, and 16.9% (43) had SID. 10.1% of the patients (17) with IC were EPC, 18.6% of the patients (8) with MID were EPC, and 74.4% of patients (32) were EPC (IC/MID vs. SID, p < 0.001). Fever was more common in the SID group than in the IC and MID groups (69.8% vs. 14.8% vs. 37.2%, p < 0.001). Of chest CT scan, most lesions were distributed under the pleura (72.7%), presenting as nodules/lumps (90.3%) or consolidations (10.7%). Pleural effusion was more common in SID group compared to IC group (33.3% vs. 2.4%, p < 0.001). Positivity rate on the serum capsular polysaccharide antigen detection (CrAg) test was higher in the SID group than in the other two groups [100.0% vs. 84.4% (MID) vs. 78.2% (IC), p = 0.013]. Positivity rate on the serum CrAg test was also higher in cryptococcal meningitis patients than in PC patients (100.0% vs. 79.5%, p = 0.015). CONCLUSIONS: The clinical presentation of MID patients is intermediate between SID and IC patients and is similar to that of IC patients. The serum CrAg test is more sensitive for the identification of SID or EPC patients.

miR-20b suppresses mitochondrial dysfunction-mediated apoptosis to alleviate hyperoxia-induced acute lung injury by directly targeting MFN1 and MFN2.

Supplemental oxygen is commonly used to treat severe respiratory failure, while prolonged exposure to hyperoxia can induce acute lung injury characterized by the accumulation of reactive oxygen species (ROS) and pulmonary inflammation. Dysregulation of microRNAs contributes to multiple diseases, including hyperoxia-induced acute lung injury (HALI). In this study, we explored the roles of miR-20b in mediating the response of type II alveolar epithelial cells (ACE IIs) to hyperoxia and the potential underlying mechanisms. We found that miR-20b was significantly decreased in the lung tissues of HALI models and H2O2-treated ACE IIs. Hyperoxia induced the release of TNF-α, decreased the mitochondrial membrane potential, and led to excessive ROS production and cell apoptosis. Overexpression of miR-20b suppressed the hyperoxia-induced biological effects in ACE IIs. miR-20b negatively regulated the expression levels of Mitofusin 1 (MFN1) and MFN2, the two key proteins of mitochondrial fusion, via complementarily binding to the 3'-untranslated regions of mRNAs. Furthermore, both in vivo and in vitro, upregulation of MFN1 and MFN2 aggravated lung damage and cell apoptosis that were alleviated by miR-20b overexpression. These results provided new insights into the involvement of the miR-20b/MFN1/2 signaling pathway in HALI.

Tuning the Electronic Structure of an α-Antimonene Monolayer through Interface Engineering.

The interfacial charge transfer from the substrate may influence the electronic structure of the epitaxial van der Waals (vdW) monolayers and, thus, their further technological applications. For instance, the freestanding Sb monolayer in the puckered honeycomb phase (α-antimonene), the structural analogue of black phosphorene, was predicted to be a semiconductor, but the epitaxial one behaves as a gapless semimetal when grown on the Td-WTe2 substrate. Here, we demonstrate that interface engineering can be applied to tune the interfacial charge transfer and, thus, the electron band of the epitaxial monolayer. As a result, the nearly freestanding (semiconducting) α-antimonene monolayer with a band gap of ∼170 meV was successfully obtained on the SnSe substrate. Furthermore, a semiconductor-semimetal crossover is observed in the bilayer α-antimonene. This study paves the way toward modifying the electron structure in two-dimensional vdW materials through interface engineering.

Probing the Thermal-Driven Structural and Chemical Degradation of Ni-Rich Layered Cathodes by Co/Mn Exchange.

The intrinsic poor thermal stability of layered LiNixCoyMn1-x-yO2 (NCM) cathodes and the exothermic side reactions triggered by the associated oxygen release are the main safety threats for their large-scale implantation. In the NCM family, it is widely accepted that Ni is the stability troublemaker, while Mn has long been considered as a structure stabilizer, whereas the role of Co remains elusive. Here, via Co/Mn exchange in a Ni-rich LiNi0.83Co0.11Mn0.06O2 cathode, we demonstrate that the chemical and structural stability of the deep delithiated NCM cathodes are significantly dominated by Co rather than the widely reported Mn. Operando synchrotron X-ray characterization coupling with in situ mass spectrometry reveal that the Co4+ reduces prior to the reduction of Ni4+ and could thus prolong the Ni migration by occupying the tetrahedra sites and, hence, postpone the oxygen release and thermal failure. In contrast, the Mn itself is stable, but barely stabilizes the Ni4+. Our results highlight the importance of evaluating the intrinsic role of compositional tuning on the Ni-rich/Co-free layered oxide cathode materials to guarantee the safe operation of high-energy Li-ion batteries.

Safety and use of pulmonary function tests: a retrospective study from a single center over seven years' clinical practice.

BACKGROUND: To promote the utilization of pulmonary function tests (PFT) through analyzing the data of PFT during the past seven years in one large teaching hospital in China. METHODS: Through a retrospective analysis, the allocation of full-time staff in PFT room, the demographic characteristics of patients, cost-effectiveness of PFT, positive rate and failure rate of PFT, adverse events were analyzed. RESULTS: 1) From 2012 to 2018, the numbers of PFT showed the trend of escalation year by year. The proportion of patients receiving PFT rose from 29.0/10,000 in 2012 to 34.7/10,000 in 2018. The best allocation of PFT room was 20-25/ person / day. 2) The number of PFT provided by Department of Pulmonary and Critical Care Medicine (PCCM) accounted for 97.2, 97.1, 97.3, 97.8, 97.8, 98.0, and 98.2% of the total cases of outpatient PFT in the same year. The top three departments in the inpatient department were Department of Thoracic Surgery, Department of General Surgery, and Department of Urinary Surgery, the total cases of PFT in these three departments accounted for 65.1, 64.4, 62.1, 63.5, 62.4, 65.3 and 69.1% of the total cases of inpatient PFT in the same year. 3) Data from 2018 showed that the revenue from PFT was about 3.7 million Chinese Yuan, and that the salary of personnel and expenditure on machine maintenance and wear were about 800,000 Chinese Yuan. 4) 58.2% of the patients who had undergone PFT had ventilatory dysfunction. 5) The average failure rate of PFT in the past seven years was 1.91%. 6) The main adverse events of PFT examination were dizziness, amaurosis, limb numbness, lip numbness and falls. The incidence rates were 0.49, 0.42, 0.41, 0.39, 0.44, 0.48, and 0.45% respectively, with an average of 0.44%. CONCLUSIONS: The number of PFT showed an upward trend in the past seven years, and the optimal staffing of PFT room was 20-25 cases per person per day. The positive rate of pulmonary dysfunction was 58.2%. The failure rate of PFT and the incidence of adverse events were very low, suggesting it is a simple and safe clinical examination. It's worthy of further popularization and promotion.

Autophagy and its role in pulmonary hypertension.

Pulmonary hypertension (PH) is a very common kind of pulmonary vascular disease, which can cause a heavier burden on patient's quality of life, even lead to death. Yet, the mechanism of PH is incomprehensive and not so clear nowadays. In recent years, more and more studies show that autophagy plays a pivotal role in the development of PH. Some modalities target on the formation or maturation of autophagosome that has emerged from our increasing knowledge of autophagy machinery, which may prevent or eliminate the process of PH. The deciphering of molecular selectivity of autophagy has also been a source of novel modulators that act specifically on selective forms of autophagy. Tremendous recent progress has opened a new possibility for modulating autophagy in complex diseases. Thus, autophagy may become a prospective choice for treatment of PH. Herein, we reviewed the literatures and discussed the role of autophagy in the development and treatment of PH.

Thioredoxin-1 maintains mechanistic target of rapamycin (mTOR) function during oxidative stress in cardiomyocytes.

Thioredoxin 1 (Trx1) is a 12-kDa oxidoreductase that catalyzes thiol-disulfide exchange reactions to reduce proteins with disulfide bonds. As such, Trx1 helps protect the heart against stresses, such as ischemia and pressure overload. Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth, metabolism, and survival. We have shown previously that mTOR activity is increased in response to myocardial ischemia-reperfusion injury. However, whether Trx1 interacts with mTOR to preserve heart function remains unknown. Using a substrate-trapping mutant of Trx1 (Trx1C35S), we show here that mTOR is a direct interacting partner of Trx1 in the heart. In response to H2O2 treatment in cardiomyocytes, mTOR exhibited a high molecular weight shift in non-reducing SDS-PAGE in a 2-mercaptoethanol-sensitive manner, suggesting that mTOR is oxidized and forms disulfide bonds with itself or other proteins. The mTOR oxidation was accompanied by reduced phosphorylation of endogenous substrates, such as S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1) in cardiomyocytes. Immune complex kinase assays disclosed that H2O2 treatment diminished mTOR kinase activity, indicating that mTOR is inhibited by oxidation. Of note, Trx1 overexpression attenuated both H2O2-mediated mTOR oxidation and inhibition, whereas Trx1 knockdown increased mTOR oxidation and inhibition. Moreover, Trx1 normalized H2O2-induced down-regulation of metabolic genes and stimulation of cell death, and an mTOR inhibitor abolished Trx1-mediated rescue of gene expression. H2O2-induced oxidation and inhibition of mTOR were attenuated when Cys-1483 of mTOR was mutated to phenylalanine. These results suggest that Trx1 protects cardiomyocytes against stress by reducing mTOR at Cys-1483, thereby preserving the activity of mTOR and inhibiting cell death.

An Alternative Way To Enhance Piezoelectricity and Temperature Stability in Lead-Free Sodium Niobate Piezoceramics.

To further balance the relationship between piezoelectricity and temperature stability, the (0.975 - y)NaNbO3- yBaTiO3-0.025BaZrO3 ( y = 0-0.20) ceramics are developed by constructing a wide tetragonal phase region. Effects of BaTiO3 on the relationships among phase structure, electrical properties, and temperature dependence are investigated. With increasing BaTiO3 contents, the ceramics endure the structural evolutions from orthorhombic phase to tetragonal phase, and then to relaxor cubic phase. A wide tetragonal phase zone of 24-180 °C can be realized in the ceramics with y = 0.08, together with an enhanced piezoelectric coefficient d33 = 215 pC/N. Intriguingly, excellent temperature stability of unipolar strain ( Suni) and piezoelectric coefficient ( d33) are observed in the ceramics with y = 0.08 within 20-180 °C. This work provides an alternative way to enhance piezoelectricity and temperature stability in lead-free piezoceramics.

A prognostic 4-gene expression signature for squamous cell lung carcinoma.

Squamous cell lung carcinoma (SQCLC), a common and fatal subtype of lung cancer, caused lots of mortalities and showed different outcomes in prognosis. This study was to screen key genes and to figure a prognostic signature to cluster the patients with SQCLC. RNA-Seq data from 550 patients with SQCLC were downloaded from The Cancer Genome Atlas (TCGA). Genetically changed genes were identified and analyzed in univariate survival analysis. Genes significantly influencing prognosis were selected with frequency higher than 100 in lasso regression. Meanwhile, area under the curve (AUC) values and hazard ratios (HR) for seed genes were obtained with R Language. Functional enrichment analysis was performed and clustering effectiveness of the selected common gene set was analyzed with Kaplan-Meier. Finally, the stability and validity of the optimal clustering model were verified. A total of 7,222 genetically changed genes were screened, including 1,045 ones with p < 0.05, 1,746, p < 0.1, and 2,758, p < 0.2. The common gene sets with more than 100 frequencies were 14-Genes, 10-Genes and 6-Genes. Genes with p < 0.05 participated in positive regulation of ERK1 and ERK2 cascade, angiogenesis, platelet degranulation, cell-matrix adhesion, extracellular matrix organization, macrophage activation, and so on. A four-gene clustering model in 14-Genes (DPPA, TTTY16, TRIM58, HKDC1, ZNF589, ALDH7A1, LINC01426, IL19, LOC101928358, TMEM92, HRASLS, JPH1, LOC100288778, GCGR) was verified as the optimal. The discovery of four-gene clustering model in 14-Genes can cluster the patient samples effectively. This model would help predict the outcomes of patients with SQCLC then improve the treatment strategies.

Sudden Cardiac Arrest Triggered by Coadministration of Fluconazole and Amiodarone.

Fluconazole for fungal infections and amiodarone for arrhythmia are commonly prescribed medications, and coadministration of such medications is sometimes inevitable in clinical practice. However, both medications have been associated with prolonged QTc intervals and subsequent arrhythmias, which are sometimes fatal. We present the case of a 75-year-old man with sudden cardiac arrest triggered by coadministration of fluconazole and amiodarone, which raises the need for caution regarding coadministration of these medications. To our knowledge, this case has not been previously described.