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Study Design: This is a report of a patient with T6 butterfly vertebra, which is an uncommon congenital spinal anomaly. Objective: To illustrate the significance of identifying butterfly vertebra that may be confused with other pathologic conditions like fractures, infections, and metastases. Summary Of Background Data: We report a 46-year-old woman with butterfly vertebra of T6 spine. The patient presented with complaints of low back pain and examination showed an abnormal bony prominence at midthoracic level. Radiologic and hematologic investigations confirmed the presence of butterfly vertebrae at T6 level, which proved to be a coincidental finding along with nonspecific low back pain. Knowledge about this condition is very important, since the condition can be easily confused with a pathologic fracture. Methods: The patient presented with a history of low back pain of 2 months. The patient was evaluated clinically and with hematological investigations. The diagnosis was confirmed with computerized tomography (CT) and magnetic resonance imaging (MRI) scans. Results: Routine examination of the motor and sensory system was found to be normal. Roentgenogram of the thoracic and lumbosacral spine showed anterior wedging of T6 vertebrae in the lateral view and features suggestive of the presence of a butterfly vertebra at T6 level in the anteroposterior (AP) view. Hematologic evaluation was done to rule out pathologic causes of anterior wedging of the vertebra like infections and metastases in the spine. MRI and CT scans of the spine confirmed the presence of T6 butterfly vertebra. Patient was treated for her low back pain and assured that the abnormal midthoracic bony prominence was a benign condition that needs no treatment. Conclusion: A high index of suspicion is needed to identify this benign spinal anomaly that may be confused with many pathologic conditions. Knowledge of this condition helps in making rational use of extensive noninvasive and invasive diagnostic procedures. [ABSTRACT FROM AUTHOR]

Lactate dehydrogenase A (LDHA) is a key enzyme in Warburg's effect, a characteristic of cancer cells. LDHA is a target of anticancer agents that inhibit the metabolism of cancer cells. Gossypol is a known cancer therapeutic agent that inhibits LDHA by competitive inhibition. However, the mechanisms of inhibition of LDHA by gossypol is unknown. Here, we elucidate the binding of gossypol and LDHA using biochemical and biophysical methods. The crystal structure of the complex between LDHA and gossypol is presented. The binding of gossypol affects LDHA activity by a conformational change in the active-site loop. Our research contributes to the structural insight into LDHA with gossypol and approaches gossypol as a novel therapeutic candidate targeting the metabolic pathways for cancer cells., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The folate metabolism enzyme ALDH1L1 catalyzed 10-formyltetrahydrofolate to tetrahydrofolate and CO 2 . Non-small cell lung cancer cells (NSCLC) strongly express ALDH1L1. Gossypol binds to an allosteric site and disrupts the folate metabolism by preventing NADP + binding. The Cryo-EM structures of tetrameric C-terminal aldehyde dehydrogenase human ALDH1L1 complex with gossypol were examined. Gossypol-bound ALDH1L1 interfered with NADP + by shifting the allosteric site of the structural conformation, producing a closed-form NADP + binding site. In addition, the inhibition activity of ALDH1L1 was targeted with gossypol in NSCLC. The gossypol treatment had anti-cancer effects on NSCLC by blocking NADPH and ATP production. These findings emphasize the structure characterizing ALDH1L1 with gossypol., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The tumor suppressor p53 plays important roles in suppressing the development and progression of cancer by responding to various stress signals. In addition, p53 can regulate the metabolic pathways of cancer cells by regulating energy metabolism and oxidative phosphorylation. Here, we present a mechanism for the interaction between p53 and ZNF568. Initially, we used X-ray crystallography to determine the irregular loop structure of the ZNF568 KRAB domain; this loop plays an important role in the interaction between p53 and ZNF568. In addition, Cryo-EM was used to examine how the p53 DBD and ZNF568 KRAB domains bind together. The function of ZNF568 on p53-mediated mitochondrial respiration was confirmed by measuring glucose consumption and lactate production. These findings show that ZNF568 can reduce p53-mediated mitochondrial respiratory activity by binding to p53 and inhibiting the transcription of SCO2. SIGNIFICANCE: ZNF568 can directly bind to the p53 DBD and transcriptionally regulate the SCO2 gene. SCO2 transcriptional regulation by interaction between ZNF568 and p53 may regulate the balance between mitochondrial respiration and glycolysis., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Enhancing learning engagement is a critical challenge in online education. While previous research underscores the importance of feedback, recent studies have shifted focus to students' perceptions of feedback, which significantly impact learning performance. However, empirical evidence on how these perceptions affect online learning outcomes is limited. Drawing on Self-Determination Theory, this study addresses this gap by employing SEM to analyze the relationships among feedback perception, academic self-efficacy, test anxiety, and online learning engagement. A total of 402 Chinese vocational college students (ages 18-19) completed questionnaires, with statistical analysis conducted using SPSS and Mplus. The study found that perception of feedback directly influences online learning engagement and indirectly affects it through academic self-efficacy and test anxiety, with a total effect value of 0.416. The findings offer valuable insights for educators and suggest directions for future research on feedback perception and online learning engagement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao and Han.)

Influenza A virus is the cause of a widespread human disease with high morbidity and mortality rates. The influenza virus encodes non-structural protein 1 (NS1), an exceedingly multifunctional virulence component. NS1 plays essential roles in viral replication and evasion of the cellular innate immune system. Protein kinase RNA-activated also known as protein kinase R (PKR) phosphorylates translation initiation factor eIF-2α on serine 51 to inhibit protein synthesis in virus-infected mammalian cells. Consequently, PKR activation inhibits mRNA translation, which results in the assert of both viral protein synthesis and cellular and possibly apoptosis in response to virus infection. Host signaling pathways are important in the replication of influenza virus, but the mechanisms involved remain to be characterized. Herein, the structure of NS1 and PKR complex was determined using Cryo-EM. We found the N91, E94, and G95 residues of PKR bind directly with N188, D125, and K126, respectively, of NS1. Furthermore, the study shows that PKR peptide offers a potential treatment for Influenza A virus infections., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

T-cell immunoglobulin and mucin protein 3 (Tim-3), also known as Hepatitis A virus cellular receptor 2, has been discovered to have a negative regulatory effect on murine T-cell responses. Galectin-9 exhibits various biological effects, including cell aggregation, eosinophil chemoattraction, activation, and apoptosis, observed in murine thymocytes, T-cells, and human melanoma cells. Such approach demonstrated that Galectin-9 acts as a binding partner on Tim-3 and mediates the T-cell inhibitory effects. Tl-gal is a homologous protein to galectin-9, isolated from the adult stage of the canine gastrointestinal nematode parasite Toxascaris leonina. However, molecular mechanism between Tim-3 and galectin-9 is still remain unknown. Here, we describe the cryo-electron microscopy and X-ray structures and interactions of the Tim-3 and Tl-gal complex as well as their biochemical and biophysical characterization. In the structure, Ser46 residue of Tl-gal NCRD was bound to Asp25 residue of hTim-3. Compared to our previous study, the binding site of the complex is the same as the sugar binding site (the Ser46 residue) of Tl-gal. In addition, analysis of the complex structure revealed that the four Tl-gal molecules were in an open form packing and one mTim-3 peptide was bound to one Tl-gal molecule. These observations suggest that how Tl-gal binds hTim3 is essential to understanding the molecular mechanism for the Tim-3-galectin 9 interaction that regulates immune responses. This could potentially serve as a therapeutic target for inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

E3L (RNA-binding protein E3) is one of the key IFN resistance genes encoded by VV and consists of 190 amino acids with a highly conserved carboxy-terminal double-stranded RNA-binding domain (dsRBD). PKR (dsRNA-dependent protein kinase) is an IFN-induced protein involved in anti-cell and antiviral activity. PKR inhibits the initiation of translation through alpha subunit of the initiation factor eIF2 (eIF2α) and mediates several transcription factors such as NF-κB, p53 or STATs. Activated PKR also induces apoptosis in vaccinia virus infection. E3L is required for viral IFN resistance and directly binds to PKR to block activation of PKR. In this work, we determined the three-dimensional complex structure of E3L and PKR using cryo-EM and determined the important residues involved in the interaction. In addition, PKR peptide binds to E3L and can increase protein levels of phosphorus-PKR and phosphorus-eIF2α-induced cell apoptosis through upregulation of phosphorus-PKR in HEK293 cells. Taken together, structural insights into E3L and PKR will provide a new optimization and development of vaccinia virus drugs., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Herein, a novel core molecule for V-shaped host molecules was synthesized, wherein two carbazoles were directly linked to cyclohexane. Cy-mCP and Cy-mCBP hosts were also successfully prepared for solution-processable thermally activated delayed fluorescence organic light-emitting diodes (TADF-OLEDs). The Cy-mCP and Cy-mCBP molecules contained a cyclohexane linker directly linked to two small molecular hosts (mCP and mCBP), exhibiting twice the molecular weight while maintaining the basic properties of a single host molecule with improved film-forming ability and solubility in organic solvents. These host materials showed superior thermal stability and high glass transition temperatures compared to lower molecular weight hosts. Green TADF-OLEDs were prepared using the two host materials and 2,4,5,6-tetra(3,6-di- tert -butylcarbazol-9-yl)-1,3-dicyanobenzene (t4CzIPN) emitter, achieving device efficiencies similar to that of a low-molecular-weight host. However, after the incorporation of a V-shaped host, superior characteristics were observed in terms of the thermal stability and operational stability of the device. The synthesis of V-shaped molecules by directly linking two carbazoles to a cyclohexane linker is promising for the development of different hosts for solution-processable OLEDs.

To obtain high-efficiency solution-processed organic light-emitting diodes (OLEDs), a hole transport material (HTM) capable of solution processing with excellent charge transport properties is required. In this study, a new vinyl polymer ( PmCP ) containing hole-transporting 1,3-di(9 H -carbazol-9-yl)benzene (mCP) in the side chain was successfully synthesized via radical polymerization. PmCP showed good film-forming ability and thermal stability. Moreover, PmCP has a higher triplet energy value and hole mobility than poly( N -vinylcarbazole) (PVK) used as a reference HTM, which can be applied as a hole transport layer (HTL) in thermally activated delayed fluorescence (TADF) OLEDs, providing green and blue emissions. PmCP -based solution-processable TADF-OLEDs containing green- and blue-emitting layers were easily fabricated without damaging the lower HTL while using ethyl acetate as an orthogonal solvent. The corresponding OLEDs possess high external quantum efficiencies of 29.60% and 11.00% for the green- and blue-emitting devices, respectively. They show superior performances compared to PVK-based devices used as a reference. It was confirmed that PmCP as a solution-processable HTM can replace PVK and is universally applicable to both green- and blue-emitting devices.

KRAS mutations occur in a quarter of all human cancers. When activated in its GTP-bound form, RAS stimulates diverse cellular systems, such as cell division, differentiation, growth, and apoptosis through the activations of various signaling pathways, which include mitogen-activated protein kinase (MAPK), phosphoinositide 3 kinases (PI3K), and RAL-GEFs pathways. We found that GJ101 ( 65 LYDVA 69 ) binds directly to the KRAS mutant (G12V) and showed tumor-suppressive activity. In addition, the GJ101 peptide inhibited KRAS mutant as determined by a [α- 32 P] guanosine triphosphate (GTP) binding assay and suppressed pancreatic cell line in a cell proliferation assay. Herein, the complex structure of KRAS and GJ101 was clarified by X-ray crystallography. Isothermal titration calorimetry showed that GJ101 binds highly with KRAS mutant and the complex structure of KRAS G12V . GJ101 complex presented that the residue of Q61 directly interacted with L65 of GJ101. Overall, the results suggest GJ101 be considered a developmental starting point for KRAS G12V inhibitor., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Fas-associated death domain (FADD) is an adapter molecule that bridges the interaction between receptor-interacting protein 1 (RIP1) and aspartate-specific cysteine protease-8 (caspase-8). As the primary mediator of apoptotic cell death, caspase-8 has two N-terminal death-effector domains (DEDs) and it interacts with other proteins in the DED subfamily through several conserved residues. In the tumor necrosis receptor-1 (TNFR-1)-dependent signaling pathway, apoptosis is triggered by the caspase-8/FADD complex by stimulating receptor internalization. However, the molecular mechanism of complex formation by the DED proteins remains poorly understood. Here, we found that direct DED-DED interaction between FADD and caspase-8 and the structure-based mutations (Y8D/I128A, E12A/I128A, E12R/I128A, K39A/I128A, K39D/I128A, F122A/I128A, and L123A/I128A) of caspase-8 disrupted formation of the stable DED complex with FADD. Moreover, the monomeric crystal structure of the caspase-8 DEDs (F122A/I128A) was solved at 1.7 Å. This study will provide new insight into the interaction mechanism and structural characteristics between FADD and caspase-8 DED subfamily proteins.

Pro-inflammatory CD4 + T helper (Th) cells drive the pathogenesis of many autoimmune conditions. Recent advances have modified views of the phenotype of pro-inflammatory Th cells in autoimmunity, extending the breadth of known Th cell subsets that operate as drivers of these responses. Heterogeneity and plasticity within Th1 and Th17 cells, and the discovery of subsets of Th cells dedicated to production of other pro-inflammatory cytokines such as GM-CSF have led to these advances. Here, we review recent progress in this area and focus specifically upon evidence for chemokine receptors that drive recruitment of these various pro-inflammatory Th cell subsets to sites of autoimmune inflammation in the CNS. We discuss expression of specific chemokine receptors by subsets of pro-inflammatory Th cells and highlight which receptors may be tractable targets of therapeutic interventions to limit pathogenic Th cell recruitment in autoimmunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Heng, Han, Abbott, McColl and Comerford.)

Purpose: We aimed to investigate the association between air pollution concentration levels and hospital admissions for heart failure (HF) among older adults in metropolitan cities in South Korea., Methods: We used hospital admission data of 1.8 million older adults in seven metropolitan cities from 2008 to 2016, derived from the National Health Insurance Service of South Korea. Daily HF admission data were linked to air pollutants concentrations for the respective dates, including particulate matter less than 2.5 μm in size (PM 2.5 ), 10 μm (PM 10 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), carbon monoxide (CO), and ozone. We estimated the association between air pollutants and daily HF admissions using quasi-Poisson generalized additive models for each city., Results: During the study period, 142,490 hospital admissions for HF were noted. Increases of 10 μg/m 3 of PM 2.5 and PM 10 , and 10 ppb of SO 2 , NO 2 , and CO were associated with an increased risk of HF admission by 0.93% ([95% confidence intervals 0.51-1.36], 0.55% [0.31-0.80], 6.04% [2.15-10.08], 1.10% [0.38-1.82], and 0.05% [0.01-0.09]), respectively, on the same day. Increases in mean exposure to PM 2.5 , PM 10 , and SO 2 for 8 days from the concurrent day were also significantly associated with HF admissions. During the warm season, the risk of HF admissions increased shortly after an increase in PM 2.5 , whereas prolonged effects were observed during the cold season., Conclusion: Our study suggests the adverse effects of air pollution on HF. Moreover, the evidence of seasonality may help tailor protection guidelines for older adults., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lipid metabolism is closely related to the improvement of vascular calcification (VC) in chronic kidney disease (CKD). Globular adiponectin (gAd) has been reported to be involved in the development of VC in CKD, but the detailed regulatory role remains unclear. The present study is aimed to investigate the biological function and the underlying regulation mechanism of gAd in the process of VC during CKD. Vascular smooth muscle cells (VSMCs) calcification was determined by Alizarin Red S staining. Protein signaling related with VC was tested by western blotting. The expression and intracellular localization of runt-related transcription factor 2 (Runx2) was detected by immunofluorescence and uraemic rat with VC was established by a two-step nephrectomy. Combined with the results of Alizarin Red S staining, we discovered that β-glycerophosphate (β-Gp)-induced the osteoblastic differentiation of VSMCs was significantly reversed by gAd treatment. Along with the VSMCs calcification and the increase of Runx2 in β-Gp-exposed VSMCs, the activities of protein kinase B (AKT) and Wnt/β-catenin pathway were enhanced, but that were counteracted by the exposure of gAd in rat and human VSMCs. After administration with agonists of the Wnt (SKL2001) and AKT (SC79), there appeared more osteoblastic differentiation and higher expression of Runx2 in gAd-treated VSMCs, but showing lower impact in the presence of SC79 than that in the presence of SKL2001. In the in vivo experiments, intravenous injection of gAd also significantly inhibited VC and Runx2 level in uraemic rat in a dose-dependent manner, possibly through regulating Wnt/β-catenin pathway. This study demonstrates that gAd ameliorates osteoblastic differentiation of VSMCs possibly by blocking PI3K/AKT and Wnt/β-catenin signaling transduction. The findings provide an important foundation for gAd in treating VC in kidney diseases., (© 2021. The Author(s).)

Rationale: Although an association of fine particulate matter (PM 2.5 ) with asthma incidence has been assumed, there is insufficient evidence regarding the effect of long-term exposure to PM 2.5 on incident asthma among elderly adults., Objectives: This study aimed to investigate an association between long-term exposure to PM 2.5 and incident asthma among elderly adults in South Korea., Methods: Adults ≥65 years of age (n = 1,220,645) who did not visit hospitals for asthma during a washout period (between 2008 and 2010) were followed up until 2016 using data from the National Health Insurance System in South Korea. Incident asthma was defined as the number of patients with a primary diagnostic code of asthma who visited hospitals more than twice. We linked the health data with district-level PM 2.5 concentrations and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident asthma after adjusting for potential confounders in time-varying Cox proportional hazard models., Measurements and Main Results: Over 5,942,256 person-years, 54,522 patients developed asthma, with an incidence of 9.2 cases/1000 person-years. A 10 μg/m 3 increase in the 36-month mean PM 2.5 concentration was significantly associated with a 9% increase in incident asthma (HR = 1.09, 95% CI: 1.04-1.14). This association was found to be robust for different definitions of incident asthma and washout periods., Conclusion: Long-term exposure to PM 2.5 was associated with the incidence of asthma in elderly adults. This finding provides evidence of an association between PM 2.5 and adult-onset asthma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Two new orange-red thermally activated delayed fluorescence (TADF) materials, PzTDBA and PzDBA, are reported. These materials are designed based on the acceptor-donor-acceptor (A-D-A) configuration, containing rigid boron acceptors and dihydrophenazine donor moieties. These materials exhibit a small ΔE ST of 0.05-0.06 eV, photoluminescence quantum yield (PLQY) as high as near unity, and short delayed exciton lifetime (τ d ) of less than 2.63 µs in 5 wt% doped film. Further, these materials show a high reverse intersystem crossing rate (k risc ) on the order of 10 6 s -1 . The TADF devices fabricated with 5 wt% PzTDBA and PzDBA as emitting dopants show maximum EQE of 30.3% and 21.8% with extremely low roll-off of 3.6% and 3.2% at 1000 cd m -2 and electroluminescence (EL) maxima at 576 nm and 595 nm, respectively. The low roll-off character of these materials is analyzed by using a roll-off model and the exciton annihilation quenching rates are found to be suppressed by the fast k risc and short delayed exciton lifetime. These devices show operating device lifetimes (LT 50 ) of 159 and 193 h at 1000 cd m -2 for PzTDBA and PzDBA, respectively. The high efficiency and low roll-off of these materials are attributed to the good electronic properties originatng from the A-D-A molecular configuration., (© 2021 Wiley-VCH GmbH.)

PUMA (p53-upregulated modulator of apoptosis) is localized in mitochondria and a direct target in p53-mediated apoptosis. p53 elicits mitochondrial apoptosis via transcription-dependent and independent mechanisms. p53 is known to induce apoptosis via the transcriptional induction of PUMA, which encodes proapoptotic BH3-only members of the Bcl-2 protein family. However, the transcription-independent mechanisms of human PUMA remain poorly defined. For example, it is not known whether PUMA interacts directly with the DNA binding domain (DBD: residues 92-293) of p53 in vitro. Here, the structure of the complex between the DBD of p53 and PUMA peptide was elucidated by X-ray crystallography. Isothermal titration calorimetry showed that PUMA peptide binds strongly with p53 DBD, and the crystal structure of p53-PUMA peptide complex revealed it contains four molecules of p53 DBD and one PUMA peptide per asymmetric unit in space group P 1 . PUMA peptide bound to the N-terminal residues of p53 DBD. A cell proliferation assay demonstrated PUMA peptide inhibited the growth of a lung cancer cell line. These results contribute to understanding of the mechanism responsible for p53-mediated apoptosis., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The KRAS oncogene is mutated in approximately ~30% of human cancers, and the targeting of KRAS has long been highlighted in many studies. Nevertheless, attempts to target KRAS directly have been ineffective. This review provides an overview of the structure of KRAS and its characteristic signaling pathways. Additionally, we examine the problems associated with currently available KRAS inhibitors and discuss promising avenues for drug development.

We report high-efficiency quantum dot light-emitting diodes (QLEDs) with Li-doped TiO 2 nanoparticles (NPs) as an alternative electron transport layer (ETL). Colloidally stable TiO 2 NPs are applied as ETLs of inverted structured QLEDs and the effect of the addition of lithium (Li) to TiO 2 NPs on device characteristics is studied in detail. Compared to pristine TiO 2 NPs, Li-doped ones are found to be beneficial for the charge balance in the emitting layer of QLEDs mainly by means of their upshifted conduction band minimum, which in turn limits electron injection. A green QLED with 5% Li-doped TiO 2 NPs produces a maximum luminance of 169 790 cd m -2 , an EQE of 10.27%, and a current efficiency of 40.97 cd A -1 , which indicate the best device performances to date among QLEDs with non-ZnO inorganic ETLs. These results indicate that Li-doped TiO 2 NPs show great promise for use as a solution-based inorganic ETL for future QLEDs.

Objective: To evaluate the performance and application of a fast nucleic acid detection system for testing severe acute respiratory syndrome virus 2 (SARS-COV-2). Methods: Clinical samples were collected from February to July 2020 from Beijing Center for Diseases Prevention and Control and the Laboratory Department of China-Japan Friendship Hospital, to evaluate the sensitivity, specificity, anti-interference ability, precision and clinical sample coincidence rate of fast nucleic acid detection system for SARS-CoV-2. The analytical sensitivity was determined by a dilution series of 20 replications for each concentration. Analytical specificity study was performed by testing organisms whose infection produces symptoms similar to those observed at the onset of corona virus disease 2019 (COVID-19), and of the normal or pathogenic microflora that may be present in specimens collected. Potential interference substances were evaluated with different concentration in the interference study. Precision study was conducted by estimating intra-and inter-batch variability. Clinical evaluation was performed by testing 230 oropharyngeal swab specimens and 95 sputum specimens in fast nucleic acid detection system, comparing with conventional real-time fluorescent quantitative PCR (RT-qPCR) and clinical diagnostic results. Results: The analytical sensitivity of SARS-CoV-2 using fast nucleic acid detection system was 400 copies/ml. The result is negative for testing with the organisms that may likely in the circulating area or causing similar symptoms with SARS-CoV-2 and human nucleic acid, indicating that no cross reactivity with organisms. The results of precision test showed that the Coefficient of variation of Ct value of high, medium and low concentration samples was 1.90%-3.92%, and all of them were less than 5% in intra-and inter-batch testing. The results of the samples were still positive after adding the potential interfering substances, indicating that the possible interfering substances in the samples had no effect on the results. 98.46% and 97.85% diagnosis results of fast nucleic acid detection system were consistent with RT-qPCR and clinical diagnostic results, respectively. Conclusion: The fast nucleic acid detection system based on molecular parallel reaction can be used as a selection method for SARS-CoV-2 testing.

BACKGROUND Pfeifer-Weber-Christian disease (PWCD), also referred to as idiopathic nodular panniculitis, is a rare idiopathic disease characterized by lobular panniculitis of adipose tissue with systemic symptoms and multiple organ involvement and is usually treated with corticosteroids and cyclosporine A. We report a case of PWCD that was unresponsive to standard treatment but responded to intravenous immune globulin (IVIG) therapy. CASE REPORT A 35-year-old Korean woman presented with fever, malaise, myalgia, and painful nodules in the left breast. Histology of the breast nodules showed lobular panniculitis consistent with PWCD. She did not respond to corticosteroid and cyclosporine A. She was effectively treated with intravenous immune globulin (IVIG). IVIG therapy began with 60 g (1 g/kg) 4 times per week, 2 times every other week. Subsequently, the IVIG dose was reduced for maintenance therapy to 25 g (400 mg/kg) twice every other week and monthly. The patient showed immediate and dramatic improvement. General signs and symptoms, such as fever, malaise, and myalgia, were absent, and the masses had nearly subsided, with several very small hard nodules remaining for 3 months until the time of this report. CONCLUSIONS IVIG was an effective immunomodulatory therapeutic for PWCD in this case. This report shows that PWCD is a rare condition that is difficult to diagnose, but the histopathology of nodular panniculitis supports the diagnosis. In cases that do not respond to standard immunosuppressive therapy, including corticosteroids and cyclosporine A, IVIG therapy may lead to a favorable response with rapid symptomatic relief.

Most cancer cells primarily produce their energy through a high rate of glycolysis followed by lactic acid fermentation even in the presence of abundant oxygen. Pyruvate dehydrogenase kinase (PDK) 1, an enzyme responsible for aerobic glycolysis via phosphorylating and inactivating pyruvate dehydrogenase (PDH) complex, is commonly overexpressed in tumors and recognized as a therapeutic target in colorectal cancer. Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata Bunge (Compositae). Here, we report that HsA is a PDK1 inhibitor can reduce the growth of colorectal cancer and consequent activation of mitochondrial ROS-dependent apoptotic pathway both in vivo and in vitro. Computational simulation and biochemical assays showed that HsA directly binds to the lipoamide-binding site of PDK1, and subsequently inhibits the interaction of PDK1 with the E2 subunit of PDH complex. As a result of PDK1 inhibition, lactate production was decreased, but oxygen consumption was increased. Mitochondrial ROS levels and mitochondrial damage were also increased. Consistent with these observations, the apoptosis of colorectal cancer cells was promoted by HsA with enhanced activation of caspase-3 and -9. These results suggested that HsA might be a potential candidate for developing a novel anti-cancer drug through suppressing cancer metabolism.

In this study, two host materials, pCzBzbCz and pCzPybCz, are synthesized to achieve a high efficiency and long lifetime of blue thermally activated delayed fluorescence organic light-emitting diodes (TADF-OLEDs). The molecular design strategy involves the introduction of a pyridine group into the core structure of pCzPybCz as an electron-withdrawing unit, and an electron-donating phenyl group into the structure of pCzBzbCz. These host materials demonstrate good thermal stability and high triplet energy (T 1 =3.07 eV for pCzBzbCz and 3.06 eV for pCzPybCz) for the fabrication of blue TADF-OLEDs. In particular, pCzPybCz-based OLED devices demonstrate an external quantum efficiency (EQE) of 22.7 % and an operational lifetime of 24 h (LT 90 , time to attain 90 % of initial luminance) at an initial luminance of 1000 cd m -2 . This superior lifetime could be explained by the C-N bond dissociation energy (BDE) in the host molecular structure. Furthermore, a mixed-host system using the electron-deficient 2,4-bis(dibenzo[b,d]furan-2-yl)-6-phenyl-1,3,5-triazine (DDBFT) is proposed to inhibit the formation of the anion state of our host materials. In short, the device operational lifetime is further improved by applying DDBFT. The carbazole-based asymmetric host molecule containing a pyridine core realizes a high-efficiency blue TADF-OLED showing a positive effect on the operating lifetime, and can provide useful strategies for designing new host materials., (© 2020 Wiley-VCH GmbH.)

The Medical Information Department of a pharmaceutical manufacturer provides written scientific responses to unsolicited requests from healthcare providers for information on products that extends beyond the product labeling (off-label). These scientific response documents are non-promotional, evidence-based, and scientifically balanced, conforming with internal pharmaceutical manufacturer's procedures and the Food and Drug Administration (FDA) Draft Guidance on Responding to Unsolicited Requests for Off-Label Information. Members of phactMI™ developed this proposal to offer best practices for content generation of scientific response documents. Scientific response documents review available literature to respond to an unsolicited request; therefore, they are similar in nature to systematic reviews. The sections and elements identified in this proposed best practice guidelines for scientific response documents are based on an adaptation of the sections and elements of systematic reviews. The sections of a scientific response document should include a restatement of the unsolicited request (title); a structured summary (abstract); approved indications, black box warnings, and background information when appropriate (introduction); the literature search information and study selection (methods); summation of data from clinical trials, meta-analysis, case reports, and/or real world evidence, as appropriate (results); treatment guidelines, if applicable and available (discussion); and references. Elements for each section should be included in a scientific response document as appropriate, as some elements are not necessary in some documents, based on the question. These elements were selected for inclusion to address any potential concerns of bias and transparency and reflect the intent that scientific response documents should be non-promotional, accurate, truthful, free of commercial bias, scientifically balanced, and evidence based.

Environmentally friendly ZnSe/ZnS core/shell quantum dots (QDs) as an alternative blue emission material to Cd-based QDs have shown great potential for use in next-generation displays. However, it remains still challenging to realize a high-efficiency quantum dot light-emitting diode (QLED) based on ZnSe/ZnS QDs due to their insufficient electrical characteristics, such as excessively high electron mobility (compared to the hole mobility) and the deep-lying valence band. In this work, the effects of QDs doped with hole transport materials (hybrid QDs) on the electrical characteristics of a QLED are investigated. These hybrid QDs show a p-type doping effect, which leads to a change in the density of the carriers. Specifically, the hybrid QDs can balance electrons and holes by suppressing the overflow of electrons and improving injection of holes, respectively. These electrical characteristics help to improve device performance. In detail, an external quantum efficiency (EQE) of 6.88% is achieved with the hybrid QDs. This is increased by 180% compared to a device with pure ZnSe/ZnS QDs (EQE of 2.46%). This record is the highest among deep-blue Cd-free QLED devices. These findings provide the importance of p-type doping effect in QD layers and guidance for the study of the electrical properties of QDs., (© 2020 Wiley-VCH GmbH.)

In cancer cells, aerobic glycolysis rather than oxidative phosphorylation (OxPhos) is generally preferred for the production of ATP. In many cancers, highly expressed pyruvate dehydrogenase kinase 1 (PDK1) reduces the activity of pyruvate dehydrogenase (PDH) by inducing the phosphorylation of its E1α subunit (PDHA1) and subsequently, shifts the energy metabolism from OxPhos to aerobic glycolysis. Thus, PDK1 has been regarded as a target for anticancer treatment. Here, we report that ilimaquinone (IQ), a sesquiterpene quinone isolated from the marine sponge Smenospongia cerebriformis , might be a novel PDK1 inhibitor. IQ decreased the cell viability of human and murine cancer cells, such as A549, DLD-1, RKO, and LLC cells. The phosphorylation of PDHA1, the substrate of PDK1, was reduced by IQ in the A549 cells. IQ decreased the levels of secretory lactate and increased oxygen consumption. The anticancer effect of IQ was markedly reduced in PDHA1-knockout cells. Computational simulation and biochemical assay revealed that IQ interfered with the ATP binding pocket of PDK1 without affecting the interaction of PDK1 and the E2 subunit of the PDH complex. In addition, similar to other pyruvate dehydrogenase kinase inhibitors, IQ induced the generation of mitochondrial reactive oxygen species (ROS) and depolarized the mitochondrial membrane potential in the A549 cells. The apoptotic cell death induced by IQ treatment was rescued in the presence of MitoTEMPO, a mitochondrial ROS inhibitor. In conclusion, we suggest that IQ might be a novel candidate for anticancer therapeutics that act via the inhibition of PDK1 activity.

Kirsten-RAS (KRAS) has been the target of drugs because it is the most mutated gene in human cancers. Because of the low affinity of drugs for KRAS mutations, it was difficult to target these tumor genes directly. We found a direct interaction between KRAS G12V and tumor suppressor novel H-REV107 peptide with high binding affinity. We report the first crystal structure of an oncogenic mutant, KRAS G12V-H-REV107. This peptide was shown to interact with KRAS G12V in the guanosine diphosphate (GDP)-bound inactive state and to form a stable complex, blocking the activation function of KRAS. We showed that the peptide acted as an inhibitor of mutant KRAS targets by [α- 32 P] guanosine triphosphate (GTP) binding assay. The H-REV107 peptide inhibited pancreatic cancer and colon cancer cell lines in cell proliferation assay. Specially, the H-REV107 peptide can suppress pancreatic tumor growth by reduction of tumor volume and weight in xenotransplantation mouse models. Overall, the results presented herein will facilitate development of novel drugs for inhibition of KRAS mutations in cancer patients.

Background: Despite the fact that thyroid surgery has evolved towards minimal incisions and endoscopic approaches, the role of total endoscopic thyroidectomy (TET) in thyroid cancer has been highly disputed. We performed a systematic review and meta-analyses of peer reviewed studies in order to evaluate the safety and effectiveness of TET compared with conventional open thyroidectomy (COT) in papillary thyroid cancer (PTC)., Method: Medical literature databases such as PubMed, Embase, the Cochrane Library, and Web of science were systematically searched for articles that compared TET and COT in PTC treatment from database inception until March 2019. The quality of the studies included in the review was evaluated using the Downs and Black scale using Review Manager software Stata V.13.0 for the meta-analysis., Results: The systematic review and meta-analysis were based on 5664 cases selected from twenty publications. Criteria used to determine surgical completeness included postoperative thyroglobulin (TG) levels, recurrence of the tumor after long-term follow-up. Adverse event and complication rate scores included transient recurrent laryngeal nerve (RLN) palsy, permanent RLN palsy, transient hypocalcaemia, permanent hypocalcaemia, operative time, number of removed lymph nodes, length of hospital stay and patient cosmetic satisfaction. TET was found to be generally equivalent to COT in terms of surgical completeness and adverse event rate, although TET resulted in lower levels of transient hypocalcemia (OR 1.66; p < 0.05), a smaller number of the retrieved lymph nodes (WMD 0.46; p < 0.05), and better cosmetic satisfaction (WMD 1.73; p < 0.05). COT was associated with a shorter operation time (WMD - 50.28; p < 0.05) and lower rates of transient RLN palsy (OR 0.41; p < 0.05)., Conclusions: The results show that in terms of safety and efficacy, TET was similar to COT for the treatment of thyroid cancer. Indeed, the tumor recurrence rates and the level of surgical completeness in TET are similar to those obtained for COT. TET was associated with significantly lower levels of transient hypocalcemia and better cosmetic satisfaction, and thus is the better option for patients with cosmetic concerns. Overall, randomized clinical trials and studies with larger patient cohorts and long-term follow-up data are required to further demonstrate the value of the TET.

In this study, the improving effects of green tea powder, soluble tea, and tea polyphenols on the mixing and tensile qualities of dough and texture of tea-enriched noodles, as well as the physico-chemical and structural properties of gluten proteins were progressively investigated. Dough strength and noodle texture were significantly increased by all the three tea products. Tea polyphenols in particular presented the most effective improvement with highest dough stability, resistance, and noodle chewiness. SEM indicated that tea products all induced a more developed gluten network, and polyphenol noodle showed the most continuous and ordered structure. FT-IR and fluorescence spectrum indicated that tea polyphenols promoted an enhancement in α-helix structure and the hydrophobic interactions. Tea polyphenols induced the SH/SS interchange during processing and cooking, and enhanced the water-solids interaction in noodles. AFM results showed that polyphenols induced the polymerization of gluten protein molecular chains, with increased chain height and width., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Angiogenesis should be precisely regulated because disordered neovascularization is involved in the aggravation of multiple diseases. The vascular endothelial growth factor (VEGF)-A/VEGF receptor 2 (VEGFR-2) axis is crucial for controlling angiogenic responses in vascular endothelial cells (ECs). Therefore, inactivating VEGFR-2 signaling may effectively suppress aberrant angiogenesis and alleviate related symptoms. In this study, we performed virtual screening, identified the synthetic disaccharide 6'-sialylgalactose (6SG) as a potent VEGFR-2-binding compound and verified its high binding affinity by Biacore assay. 6SG effectively suppressed VEGF-A-induced VEGFR-2 phosphorylation and subsequent in vitro angiogenesis in HUVECs without inducing cytotoxicity. 6SG also inhibited VEGF-A-induced extracellular-regulated kinase (ERK)/Akt activation and actin stress fiber formation in HUVECs. We demonstrated that 6SG inhibited retinal angiogenesis in a mouse model of retinopathy of prematurity and tumor angiogenesis in a xenograft mouse model. Our results suggest a potential therapeutic benefit of 6SG in inhibiting angiogenesis in proangiogenic diseases, such as retinopathy and cancer.

The influenza A virus is a highly infectious respiratory pathogen that sickens many people with respiratory disease annually. To prevent outbreaks of this viral infection, an understanding of the characteristics of virus-host interaction and development of an anti-viral agent is urgently needed. The influenza A virus can infect mammalian species including humans, pigs, horses and seals. Furthermore, this virus can switch hosts and form a novel lineage. This so-called zoonotic infection provides an opportunity for virus adaptation to the new host and leads to pandemics. Most influenza A viruses express proteins that antagonize the antiviral defense of the host cell. The non-structural protein 1 (NS1) of the influenza A virus is the most important viral regulatory factor controlling cellular processes to modulate host cell gene expression and double-stranded RNA (dsRNA)-mediated antiviral response. This review focuses on the influenza A virus NS1 protein and outlines current issues including the life cycle of the influenza A virus, structural characterization of the influenza A virus NS1, interaction between NS1 and host immune response factor, and design of inhibitors resistant to the influenza A virus.

Background: The aim of this study was to compare radiofrequency ablation (RFA) with minimally invasive liver surgery (MIS) in the treatment of small hepatocellular carcinoma (SHCC) and to assess short-term and long-term clinical outcomes., Methods: PubMed, Embase, Cochrane Library, Web of science, and CBM were systematically searched for articles from inception to July 2018, comparing RFA and MIS in SHCC treatment. We evaluated overall survival (OS), disease-free survival (DFS), local recurrence, and complication rates, as well as hospitalization duration and operation times., Results: Six retrospective studies were analyzed, including a total of 597 patients, 313 treated with RFA and 284 treated with MIS. OS rates were significantly higher in patients treated with MIS at 3 years, when compared to RFA (OR 0.55; 95% CI 0.36 to 0.84). The 3-year DFS MIS rates were also superior to RFA (OR 0.63; 95% CI 0.41 to 0.98). In contrast, when compared to MIS, RFA demonstrated a significantly higher rate of local intrahepatic recurrences, (OR 2.24; 95% CI 1.47 to 3.42), and a lower incidence of postoperative complications (OR 0.34; 95% CI 0.22 to 0.53), as well as shorter operation times (OR - 145.31, 95% CI - 200.24 to - 90.38) and hospitalization duration (OR - 4.02,95% CI - 4.94 to - 3.10)., Conclusions: We found that MIS led to higher OS, DFS, and lower local recurrences in SHCC patients. Meanwhile, RFA treatments led to significantly lower complication rates, shorter operation times, and hospitalization duration. Considering long-term outcomes, MIS was found to be superior to RFA. However, RFA may be an alternative treatment for patients presenting a single SHCC nodule (≤ 3 cm), given its minimally invasive nature and its comparable long-term efficacy with MIS. Nevertheless, our findings should be explained with caution due to the low level of evidence obtained.

In this study, the inhibiting effects of low-molecular weight polyols on the deterioration of gluten network and noodle texture were systematically investigated, based on dough rheological properties, and the macroscopic, structural and water status changes of gluten protein during storage of fresh noodles. Both glycerol and propylene glycol significantly restrained the decrease of GMP gel weight, LA-SRC value, hardness and springiness, and the increase of cooking loss. SEM showed that polyols retarded the collapse of gluten network, with still continuous gluten fibrils. The inner structure of polyol noodles was much less damaged after 2 days, with more uniform moisture distribution in MRI images. Potential dynamic depolymerization and repolymerization interactions were detected for protein components during processing and cooking, which might contribute to the textural changes. Low-molecular weight polyols inhibited the collapse of gluten network and deterioration of noodle texture although they showed no inhibiting effect on microbial growth., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lactate dehydrogenase A (LDHA) is an important enzyme responsible for cancer growth and energy metabolism in various cancers via the aerobic glycolytic pathway. Here, we report that machilin A (MA), which acts as a competitive inhibitor by blocking the nicotinamide adenine dinucleotide (NAD) binding site of LDHA, suppresses growth of cancer cells and lactate production in various cancer cell types, including colon, breast, lung, and liver cancers. Furthermore, MA markedly decreased LDHA activity, lactate production, and intracellular adenosine triphosphate (ATP) levels induced by hypoxia-induced LDHA expression in cancer cells, and significantly inhibited colony formation, leading to reduced cancer cell survival. In mouse models inoculated with murine Lewis lung carcinoma, MA significantly suppressed tumor growth as observed by a reduction of tumor volume and weight; resulting from the inhibition of LDHA activity. Subsequently, the suppression of tumor-derived lactic acid in MA-treated cancer cells resulted in decrease of neovascularization through the regulation of alternatively activated macrophages (M2) polarization in macrophages. Taken together, we suggest that the reduction of lactate by MA in cancer cells directly results in a suppression of cancer cell growth. Furthermore, macrophage polarization and activation of endothelial cells for angiogenesis were indirectly regulated preventing lactate production in MA-treated cancer cells.

Purpose: The aim of this meta-analysis was to compare high inferior mesenteric artery (IMA) ligation (HL) with low IMA ligation (LL) for the treatment of colorectal cancer and to evaluate the lymph node yield, survival benefit, and safety of these surgeries., Methods: PubMed, Embase, Cochrane Library, Web of Science, and China Biomedical Literature Database (CBM) were systematically searched for relevant articles that compared HL and LL for sigmoid or rectal cancer. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference (WMD) for continuous outcomes., Results: In total, 30 studies were included in this analysis. There were significantly higher odds of anastomotic leakage and urethral dysfunction in patients treated with HL compared to those treated with LL (OR = 1.29; 95% CI = 1.08 to 1.55; OR = 2.45; 95% CI = 1.39 to 4.33, respectively). There were no significant differences between the groups in terms of the total number of harvested lymph nodes, the number of harvested lymph nodes around root of the IMA, local recurrence rate, and operation time. Further, no statistically significant group differences in 5-year overall survival rates and 5-year disease-free survival rates were detected among all patients nor among subgroups of stage II patients and stage III patients, respectively., Conclusions: LL can achieve equivalent lymph node yield to HL, and both procedures have similar survival benefits. However, LL is associated with a lower incidence of leakage and urethral dysfunction. Thus, LL is recommended for colorectal cancer surgery.

Aerobic glycolysis is one of the important metabolic characteristics of many malignant tumors. Pyruvate dehydrogenase kinase (PDHK) plays a key role in aerobic glycolysis by phosphorylating the E1α subunit of pyruvate dehydrogenase (PDH). Hence, PDHK has been recognized as a molecular target for cancer treatment. Here, we report that huzhangoside A (Hu.A), a triterpenoid glycoside compound isolated from several plants of the Anemone genus, acts as a novel PDHK inhibitor. Hu.A was found to decrease the cell viability of human breast cancer MDA-MB-231, hepatocellular carcinoma Hep3B, colon cancer HT-29, DLD-1, and murine lewis lung carcinoma LLC cell lines. The activity of PDHK1 was decreased by Hu.A in both in vitro assays and in vivo assays in DLD-1 cells. Hu.A significantly increased the oxygen consumption and decreased the secretory lactate levels in DLD-1 cells. In addition, Hu.A interacted with the ATP-binding pocket of PDHK1 without affecting the interaction of PDHK1 and pyruvate dehydrogenase complex (PDC) subunits. Furthermore, Hu.A significantly induced mitochondrial reactive oxygen species (ROS) and depolarized the mitochondrial membrane potential in DLD-1 cells. Consistently, when Hu.A was intraperitoneally injected into LLC allograft mice, the tumor growth was significantly decreased. In conclusion, Hu.A suppressed the growth of tumors in both in vitro and in vivo models via inhibition of PDHK activity.

The Warburg effect, wherein cancer cells prefer glycolysis rather than oxidative phosphorylation even under normoxic conditions, is a major characteristic of malignant tumors. Lactate dehydrogenase A (LDHA) is the main enzyme regulating the Warburg effect, and is thus, a major target for novel anti-cancer drug development. Through our ongoing screening of novel inhibitors, we found that several selenobenzene compounds have inhibitory effects on LDHA activity. Among them, 1-(phenylseleno)-4-(trifluoromethyl) benzene (PSTMB) had the most potent inhibitory effect on the enzymatic activity of LDHA. The results from biochemical assays and computational modeling showed that PSTMB inhibited LDHA activity. In addition, PSTMB inhibited the growth of several tumor cell lines, including NCI-H460, MCF-7, Hep3B, A375, HT29, and LLC. In HT29 human colon cancer cells, PSTMB dose-dependently inhibited the viability of the cells and activity of LDHA, without affecting the expression of LDHA. Under both normoxic and hypoxic conditions, PSTMB effectively reduced LDHA activity and lactate production. Furthermore, PSTMB induced mitochondria-mediated apoptosis of HT29 cells via production of reactive oxygen species. These results suggest that PSTMB may be a novel candidate for development of anti-cancer drugs by targeting cancer metabolism.

This meta-analysis aimed to compare the effectiveness of the suprapubic drainage and urethral catheterization after robot-assisted radical prostatectomy (RARP). PubMed, EMBASE, Cochrane Library and China Biology Medicine disc were systematically researched from their inception to December 2017. We selected randomized controlled trials, cohort studies comparing suprapubic tube with urethral catheter drainage in RARP patients. A meta-analysis was performed using R software, and a random-effects model was used to pool the effect size. Ten studies met eligibility criteria (N = 1248), including 3 RCTs, 3 prospective studies and 4 retrospective studies. Suprapubic drainage was associated with a reduction in the penile pain (39.64% [44 of 111]) compared with the UC group (62% [106 of 171]) (pooled RR 0.57, 95% CI 0.31 to 1.02, P = 0.05). However, two groups showed similarity in the overall pain (Postoperative days 1-3: pooled MD -0.26, 95% CI 1.34 to 0.83, P = 0.64; Postoperative days 6-7: pooled MD -0.50, 95% CI -1.54 to 0.54, P = 0.34), urinary incontinence (pooled RR 0.80, 95% CI 0.56 to 1.15, P = 0.23), bladder neck contracture (pooled RR 0.77, 95% CI 0.39 to 1.53, P = 0.45), urinary retention (pooled RR 0.88, 95% CI 0.29 to 2.70, P = 0.82), anastomotic stricture (P = 0.15), urethral stricture (P = 0.84) and bacteriuria (P = 0.40). The present meta-analysis showed that suprapubic drainage may be associated with less penile pain, but there was no conclusive evidence that suprapubic drainage was advantaged in other outcomes. Due to the low quality and small quantity of the available comparative studies, more high-quality randomized trials are needed to provide stronger evidence of the benefits of the two routes., (Copyright © 2018. Published by Elsevier Taiwan LLC.)