Identification of a novel nonsense ATP2A2 gene variant in a patient with Darier's disease flare following COVID-19 infection: A case report.

RATIONALE: Darier disease (DD) is a rare autosomal dominant disorder that primarily manifests as hyperkeratotic papules and itching. The underlying etiology of DD is pathogenic variation in the ATP2A2 gene. However, this disease has a high penetrance but variable expressivity, indicating that patients inheriting the genotype may have different manifestations due to exogenous factors. Meanwhile, a few reports have documented that COVID-19 may be implicated in the flare of DD. PATIENT CONCERNS: A 51-year-old man presented with keratotic papules and scaly erythematous rash on his trunk with pruritus after being infected with COVID-19. Laboratory test results were normal. Histological analysis revealed epidermal hyperkeratosis and intraepidermal lacunae containing dyskeratinized cells. Genetic analysis revealed a novel variant of ATP2A2 (c.815G>A, p.Trp272*), which was considered pathogenic in this case. DIAGNOSES: The patient was diagnosed as having DD. INTERVENTIONS: Oral acitretin and topical corticosteroid hormone ointments were used. OUTCOMES: The patient achieved complete resolution of symptoms during the 3-month follow-up period. LESSONS: We revealed the first novel ATP2A2 variant (c.815G>A, p.Trp272*) in the flare of DD following COVID-19 infection. Additionally, this pathogenic variant enriches the ATP2A2 gene mutation spectrum.

RODFormer: High-Precision Design for Rotating Object Detection with Transformers.

Aiming at the problem of Transformers lack of local spatial receptive field and discontinuous boundary loss in rotating object detection, in this paper, we propose a Transformer-based high-precision rotating object detection model (RODFormer). Firstly, RODFormer uses a structured transformer architecture to collect feature information of different resolutions to improve the collection range of feature information. Secondly, a new feed-forward network (spatial-FFN) is constructed. Spatial-FFN fuses the local spatial features of 3 × 3 depthwise separable convolutions with the global channel features of multilayer perceptron (MLP) to solve the deficiencies of FFN in local spatial modeling. Finally, based on the space-FFN architecture, a detection head is built using the CIOU-smooth L1 loss function and only returns to the horizontal frame when the rotating frame is close to the horizontal, so as to alleviate the loss discontinuity of the rotating frame. Ablation experiments of RODFormer on the DOTA dataset show that the Transformer-structured module, the spatial-FFN module and the CIOU-smooth L1 loss function module are all effective in improving the detection accuracy of RODFormer. Compared with 12 rotating object detection models on the DOTA dataset, RODFormer has the highest average detection accuracy (up to 75.60%), that is, RODFormer is more competitive in rotating object detection accuracy.

Circ_0005320 promotes oral squamous cell carcinoma tumorigenesis by sponging microRNA-486-3p and microRNA-637.

Circ_0005320 was found to be elevated in oral squamous cell carcinoma (OSCC) and accelerated OSCC progression. Here, the potential mechanism of circ_0005320 in OSCC tumorigenesis was explored. The quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to detect the expression of circ_0005320, miR-486-3p, and miR-637. In vitro assays were conducted using cell counting kit-8, colony formation, transwell, angiogenesis, and flow cytometry assays. The targeting relationship between microRNA (miR)-486-3p and miR-637 or circ_0005320 was confirmed using the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway-related proteins were analyzed using Western blot. The murine xenograft model was established to perform in vivo assay. Circ_0005320 expression was higher in OSCC tissues and cells. Knockdown of circ_0005320 suppressed OSCC cell growth, migration, invasion, and induced cell apoptosis in vitro, as well as impeded tumor growth in vivo. Mechanistically, miR-486-3p or miR-637 were confirmed to be a target of circ_0005320. Moreover, the inhibitory effects of circ_0005320 silencing on OSCC growth were reversed by the inhibition of miR-486-3p or miR-637. We also found that circ_0005320-miR-486-3p/miR-637 axis mediated the activation of JAK2/STAT3 pathway. This study revealed a novel regulatory network of circ_0005320-miR-486-3p/miR-637 axis in OSCC progression, suggesting that circ_0005320 might be a potential biomarker and therapeutic target for OSCC.

LC-MS-based identification and antioxidant evaluation of small molecules from the cinnamon oil extraction waste.

Cinnamon oil is obtained by steam distillation from cinnamon leaves and is usually considered highly cost-effective compared to bark oil, however, which results in tons of waste cinnamon leaves (WCL) discarded annually. By using MS/MS molecular networking (MN) assisted profiling, six main chemical diversities including flavonols and flavones, phenolic acids, lactones, terpenoids, phenylpropanoids and flavanols were rapid revealed from WCL aqueous extract. 101 compounds were tentatively identified by assigning their MS/MS fragments within typical pathways under ESI-MS/MS dissociation. The featured phenolic acids, terpenoids and their glycosides in cinnamon species were recognized as the main constituents of WCL. The hydrophilic lactones, lignans and flavanols were reported for the first time in cinnamon leaves. Furthermore, ABTS and FRAP assays integrated with MN analysis were conducted to uncover an antioxidant fraction, from which 40 potential antioxidant compounds were rapidly annotated. This fundamental information will help expand the utilization of WCL from cinnamon oil industry.

FGFR/RACK1 interacts with MDM2, promotes P53 degradation, and inhibits cell senescence in lung squamous cell carcinoma.

OBJECTIVE: FGFR is considered an important driver gene of lung squamous cell carcinoma (LSCC). Thus, identification of the biological events downstream of FGFR is important for the treatment of this malignancy. Our previous study has shown that the FGFR/RACK1 complex interacts with PKM2 and consequently promotes glycolysis in LSCC cells. However, the biological functions of the FGFR/RACK1 complex remain poorly understood. METHODS: Anchorage-independent assays and in vivo tumorigenesis assays were performed to evaluate cancer cell malignancy. Distant seeding assays were performed to evaluate cancer cell metastasis. ß-gal staining was used to examine cell senescence, and immunoprecipitation assays were performed to examine the interactions among FGFR, RACK1, and MDM2. RESULTS: FGFR/RACK1 was found to regulate the senescence of LSCC cells. Treatment with PD166866, an inhibitor of FGFR, or knockdown of RACK1 induced senescence in LSCC cells (P < 0.01). A molecular mechanistic study showed that FGFR/RACK1/MDM2 form a complex that promotes the degradation of p53 and thus inhibits cell senescence. PD166866 and RG7112, an MDM2/p53 inhibitor, cooperatively inhibited the colony formation and distal seeding of LSCC cells (P < 0.01), and upregulated the expression of p53 and p21. CONCLUSIONS: Together, our findings revealed the regulatory roles and mechanisms of FGFR/RACK1 in cell senescence. This understanding should be important in the treatment of LSCC.

Mechanical characteristics of medical grade UHMWPE under dynamic compression.

The mechanical properties of medical grade ultrahigh molecular weight polyethylene (UHMWPE) are critical for the safety and integrity of UHMWPE implantation. Accordingly, the mechanical features of UHMWPE are tested under repeated stress-controlled and strain-controlled compression at room temperature. Some important effect factors, such as stress rate, mean stress, stress amplitude, strain rate, mean strain, strain range and multiple load steps are further considered in detail. Results indicate that the lower stress rate causes the greater accumulated plastic strain and the accumulated plastic strain rate becomes increasingly lower with increasing number of cycles. The strain range and accumulated plastic strain rate decrease rapidly in the first stage, and then become almost steady during the second stage. Especially, the accumulated plastic strain rate per cycle for each case is less than 0.01 %/cycle after the initial 100 cycles. This means that the plastic strain accumulates very slowly and the shakedown behavior always occurs. Moreover, obvious cyclic softening and stress relaxation behaviors can be observed under cyclic strain-controlled compression during the first 50 cycles. This indicates that the accumulated plastic stain in the initial 100 cycles and the cyclic stress relaxation during the first 50 cycles should be assessed for the functionality of UHMWPE implantation.

Icariin promotes the migration of bone marrow stromal cells via the SDF-1α/HIF-1α/CXCR4 pathway.

PURPOSE: In this study, a series of in vitro experiments were performed to investigate the molecular mechanisms underlying cell migration promoted by icariin (ICA) at low concentrations. MATERIALS AND METHODS: Bone marrow stromal cells (BMSCs) were cultured with different concentrations of ICA to verify whether it can enhance the efficiency of BMSCs migration. Western blot was employed to measure the expression of hypoxia-inducible factor-1α (HIF-1α) and C-X-C chemokine receptor type 4 (CXCR4) at different time points in BMSCs treated with ICA. Subsequently, we evaluated the function of HIF-1α in the expression of CXCR4 and the migration of cells by transfecting plasmid HIF-1α small interfering RNA (siHIF-1α) into BMSCs model. RESULTS: Our data indicated that different concentrations of ICA (10, 1, and 0.1 µM) further enhanced the chemotactic capability of SDF-1α, and the most prominent cell migration stimulatory effect was observed with 1 µM ICA. Furthermore, ICA significantly enhanced the protein levels of CXCR4 and HIF-1α, and this effect was blocked by ICI 12,780 (estrogen receptor antagonis). Moreover, transfection of BMSCs with siHIF-1α reduced CXCR4 expression, suggesting that HIF-1α can regulate the migration of cells by influencing the expression of CXCR4. CONCLUSION: ICA promoted BMSCs migration via the activation of HIF-1α and further regulated the expression of CXCR4, suggesting that ICA might have beneficial effects in stem cell therapy.

rGO Functionalized with a Highly Electronegative Keplerate-Type Polyoxometalate for High-Energy-Density Aqueous Asymmetric Supercapacitors.

Keplerate-type polyoxometalates represent a large series of high nuclear molecular clusters; for example, (NH4 )42 [MoVI 72 MoV 60 O372 (CH3 COO)30 (H2 O)72 ] ({Mo132 }) is a kind of spherical heteropoly blue with a large overall negative charge and an electron density and topological structure similar to C60 . {Mo132 } is a good bifunctional material that can be used as an electron acceptor or donor, which is advantageous to accelerate electron transmission in supercapacitors. Herein, a nanocomposite of rGO functionalized with a Keplerate-type polyoxometalate {Mo132 } was prepared by a facile chemical reduction method and used to construct supercapacitors for the first time. The electrochemical performance of the supercapacitors can be significantly improved due to the excellent redox properties, high electronegativity, and hollow porous structures of {Mo132 }, in addition to the outstanding conductivity of rGO. The {Mo132 }-rGO nanocomposite electrode exhibited an excellent gravimetric specific capacitance of 617.3 F g-1 at a current density of 5 A g-1 in 1 m Li2 SO4 electrolyte. An aqueous asymmetric supercapacitor with a voltage range of 2.1 V, with the {Mo132 }-rGO nanocomposite as the negative electrode and modified activated carbon as the positive electrode, exhibited a high energy density of 31.6 Wh kg-1 with a power density of 207.7 W kg-1 and favorable cycling stability.

A Reusable N-Doped-Carbon-Coated Mo2 C Composite Counter Electrode for High-Efficiency Dye-Sensitized Solar Cells.

The design and development of efficient and stable nonprecious-metal-based catalysts for counter electrodes (CEs) in dye-sensitized solar cells (DSSCs) has received a great deal of attention. In this work, molybdenum carbide nanoparticles homogeneously distributed in a nitrogen-rich carbon matrix (Mo2 C@NC) have been synthesized from inexpensive raw materials (polyoxometalate and dicyandiamide) by a facile one-step solid-phase synthesis method. The novel Mo2 C@NC hybrid was not only used as a CE in a DSSC, but also showed superior catalytic activity towards I3- /I- as a redox electrolyte. The power conversion efficiency of a DSSC with Mo2 C@NC as the CE was as high as 6.49 %, comparable to that with Pt (6.38 %). The CE was prepared by a drop-coating method, without the addition of another conductive polymer. Most importantly, the method circumvents the problem of the sample falling off from the fluorine-doped tin oxide (FTO), and the CE could be repeatedly reused with unchanged efficiency. Therefore, it opens the way for the development of platinum-free catalysts with low cost, simple processing, good stability, and high efficiency.

A Strategy for Breaking Polyoxometalate-based MOFs To Obtain High Loading Amounts of Nanosized Polyoxometalate Clusters to Improve the Performance of Dye-sensitized Solar Cells.

Polyoxometalates (POM) have already been confirmed to act as effective electron-transfer mediators for improving the power conversion efficiency (PCE) of dye-sensitized solar cells (DSSCs) based on previous studies. However, the improvement may be limited by the agglomeration of the polyoxoanions. In this paper, the previous synthesis strategy is improved upon by breaking the metal-organic frameworks (MOFs) with POMs as the secondary building units ([Ni(bpp)(H2 O)2 ]3 [P2 W18 O62 ]⋅24 H2 O (1) (bpp=1,3-bis(4-pyridyl)propane) and H6 [Cu3 (H2 O)6 (P2 W18 O62 )2 (3-dpye)6 ]⋅28 H2 O (2) (3-dpye=N,N'-bis(3-pyridinecarboxamide)-1,2-ethane)) to design and synthesize small sized and highly disperse POM nanoparticles by means of compositing with TiO2 , through calcination to remove the organic ligand. TEM and element mapping confirm that P2 W18 O626- (denoted as P2 W18 ) nanoparticles with the diameter of ≈1 nm are uniformly distributed in TiO2 composites. The loading amount (wt. %) of POM in MOFs reaches 75.67 %. The small sized and highly disperse P2 W18 nanoparticles may provide more active sites and specific surface areas for improving the PCE of DSSCs. Finally, the investigations indicate that the PCE of composite P2 W18 ⋅NiO@TiO2 photoanodes is up to 7.56 %, which was 26 % higher than the pristine TiO2 based photoanodes.