Exploring the Key Amino Acid Residues Surrounding the Active Center of Lactate Dehydrogenase A for the Development of Ideal Inhibitors.

Lactate dehydrogenase A (LDHA) primarily catalyzes the conversion between lactic acid and pyruvate, serving as a key enzyme in the aerobic glycolysis pathway of sugar in tumor cells. LDHA plays a crucial role in the occurrence, development, progression, invasion, metastasis, angiogenesis, and immune escape of tumors. Consequently, LDHA not only serves as a biomarker for tumor diagnosis and prognosis but also represents an ideal target for tumor therapy. Although LDHA inhibitors show great therapeutic potential, their development has proven to be challenging. In the development of LDHA inhibitors, the key active sites of LDHA are emphasized. Nevertheless, there is a relative lack of research on the amino acid residues around the active center of LDHA. Therefore, in this study, we investigated the amino acid residues around the active center of LDHA. Through structure comparison analysis, five key amino acid residues (Ala30, Met41, Lys131, Gln233, and Ala259) were identified. Subsequently, the effects of these five residues on the enzymatic properties of LDHA were investigated using site-directed mutagenesis. The results revealed that the catalytic activities of the five mutants varied to different degrees in both the reaction from lactic acid to pyruvate and pyruvate to lactic acid. Notably, the catalytic activities of LDHAM41G and LDHAK131I were improved, particularly in the case of LDHAK131I. The results of the molecular dynamics analysis of LDHAK131I explained the reasons for this phenomenon. Additionally, the optimum temperature of LDHAM41G and LDHAQ233M increased from 35 °C to 40 °C, whereas in the reverse reaction, the optimum temperature of LDHAM41G and LDHAK131I decreased from 70 °C to 60 °C. These findings indicate that Ala30, Met41, Lys131, Gln233, and Ala259 exert diverse effects on the catalytic activity and optimum temperature of LHDA. Therefore, these amino acid residues, in addition to the key catalytic site of the active center, play a crucial role. Considering these residues in the design and screening of LDHA inhibitors may lead to the development of more effective inhibitors.

Hypoxia-inducible factor in breast cancer: role and target for breast cancer treatment.

Globally, breast cancer stands as the most prevalent form of cancer among women. The tumor microenvironment of breast cancer often exhibits hypoxia. Hypoxia-inducible factor 1-alpha, a transcription factor, is found to be overexpressed and activated in breast cancer, playing a pivotal role in the anoxic microenvironment by mediating a series of reactions. Hypoxia-inducible factor 1-alpha is involved in regulating downstream pathways and target genes, which are crucial in hypoxic conditions, including glycolysis, angiogenesis, and metastasis. These processes significantly contribute to breast cancer progression by managing cancer-related activities linked to tumor invasion, metastasis, immune evasion, and drug resistance, resulting in poor prognosis for patients. Consequently, there is a significant interest in Hypoxia-inducible factor 1-alpha as a potential target for cancer therapy. Presently, research on drugs targeting Hypoxia-inducible factor 1-alpha is predominantly in the preclinical phase, highlighting the need for an in-depth understanding of HIF-1α and its regulatory pathway. It is anticipated that the future will see the introduction of effective HIF-1α inhibitors into clinical trials, offering new hope for breast cancer patients. Therefore, this review focuses on the structure and function of HIF-1α, its role in advancing breast cancer, and strategies to combat HIF-1α-dependent drug resistance, underlining its therapeutic potential.

Constructing Hollow Microcubes SnS2 as Negative Electrode for Sodium-ion and Potassium-ion Batteries.

Sodium/potassium-ion batteries (NIBs and KIBs) are considered the most promising candidates for lithium-ion batteries in energy storage fields. Tin sulfide (SnS2) is regarded as an attractive negative candidate for NIBs and KIBs thanks to its superior power density, high-rate performance and natural richness. Nevertheless, the slow dynamics, the enormous volume change and the decomposition of polysulfide intermediates limit its practical application. Herein, microcubes SnS2 were prepared through sacrificial MnCO3 template-assisted and a facile solvothermal reaction strategy and their performance was investigated in Na and K-based cells. The unique hollow cubic structure and well-confined SnS2 nanosheets play an important role in Na+/K+ rapid kinetic and alleviating volume change. The effect of the carbon additives (Super P/C65) on the electrochemical properties were investigated thoroughly. The in operando and ex-situ characterization provide a piece of direct evidence to clarify the storage mechanism of such conversion-alloying type negative electrode materials.

Stabilizing Top Interface by Molecular Locking Strategy with Polydentate Chelating Biomaterials toward Efficient and Stable Perovskite Solar Cells in Ambient Air.

The instability of top interface induced by interfacial defects and residual tensile strain hinders the realization of long-term stable n-i-p regular perovskite solar cells (PSCs). Herein, one molecular locking strategy is reported to stabilize top interface by adopting polydentate ligand green biomaterial 2-deoxy-2,2-difluoro-d-erythro-pentafuranous-1-ulose-3,5-dibenzoate (DDPUD) to manipulate the surface and grain boundaries of perovskite films. Both experimental and theoretical evidence collectively uncover that the uncoordinated Pb2+ ions, halide vacancy, and/or I─Pb antisite defects can be effectively healed and locked by firm chemical anchoring on the surface of perovskite films. The ingenious polydentate ligand chelating is translated into reduced interfacial defects, increased carrier lifetimes, released interfacial stress, and enhanced moisture resistance, which should be liable for strengthened top interface stability and inhibited interfacial nonradiative recombination. The universality of the molecular locking strategy is certified by employing different perovskite compositions. The DDPUD modification achieves an enhanced power conversion efficiency (PCE) of 23.17-24.47%, which is one of the highest PCEs ever reported for the devices prepared in ambient air. The unsealed DDPUD-modified devices maintain 98.18% and 88.10% of their initial PCEs after more than 3000 h under a relative humidity of 10-20% and after 1728 h at 65 °C, respectively.

Polydentate Ligand Reinforced Chelating to Stabilize Buried Interface toward High-Performance Perovskite Solar Cells.

The instability of the buried interface poses a serious challenge for commercializing perovskite photovoltaic technology. Herein, we report a polydentate ligand reinforced chelating strategy to strengthen the stability of buried interface by managing interfacial defects and stress. The bis(2,2,2-trifluoroethyl) (methoxycarbonylmethyl)phosphonate (BTP) is employed to manipulate the buried interface. The C=O, P=O and two -CF3 functional groups in BTP synergistically passivate the defects from the surface of SnO2 and the bottom surface of the perovskite layer. Moreover, The BTP modification contributes to mitigated interfacial residual tensile stress, promoted perovskite crystallization, and reduced interfacial energy barrier. The multidentate ligand modulation strategy is appropriate for different perovskite compositions. Due to much reduced nonradiative recombination and heightened interface contact, the device with BTP yields a promising power conversion efficiency (PCE) of 24.63 %, which is one of the highest efficiencies ever reported for devices fabricated in the air environment. The unencapsulated BTP-modified devices degrade to 98.6 % and 84.2 % of their initial PCE values after over 3000 h of aging in the ambient environment and after 1728 h of thermal stress, respectively. This work provides insights into strengthening the stability of the buried interface by engineering multidentate chelating ligand molecules.

A Bimetallic Organic Framework with Mn in MIL-101(Cr) for Lithium-Sulfur Batteries.

Lithium-sulfur batteries (LSBs) show excellent performance in terms of specific capacity and energy density. However, the cyclic stability of LSBs is compromised due to the "shuttle effect", which hinders the practical applications of LSBs. Herein, a metal-organic framework (MOF) based on Cr ions as the main body composition, commonly known as MIL-101(Cr), was utilized to minimize the shuttle effect and improve the cyclic performance of LSBs. To obtain MOFs with a certain adsorption capacity for lithium polysulfide and a certain catalytic capacity, we propose an effective strategy of incorporating sulfur-loving metal ions (Mn) into the skeleton to enhance the reaction kinetics at the electrode. Based on the oxidation doping method, Mn2+ was uniformly dispersed in MIL-101(Cr) to produce bimetallic Cr2O3/MnOx as a novel sulfur-carrying cathode material. Then, a sulfur injection process was carried out by melt diffusion to obtain the sulfur-containing Cr2O3/MnOx-S electrode. Moreover, an LSB assembled with Cr2O3/MnOx-S showed improved first-cycle discharge (1285 mAh·g-1 at 0.1 C) and cyclic performance (721 mAh·g-1 at 0.1 C after 100 cycles), and the overall performance was much better than that of monometallic MIL-101(Cr) as a sulfur carrier. These results revealed that the physical immobilization method of MIL-101(Cr) positively affected the adsorption of polysulfides, while the bimetallic composite Cr2O3/MnOx formed by the doping of sulfur-loving Mn2+ into the porous MOF produced a good catalytic effect during LSB charging. This research provides a novel approach for preparing efficient sulfur-containing materials for LSBs.

Single-Molecule Tracking of Reagent Diffusion during Chemical Reactions.

Recent experiments have shown that the diffusion of reagent molecules is inconsistent with what the Stokes-Einstein equation predicts during a chemical reaction. Here, we used single-molecule tracking to observe the diffusion of reactive reagent molecules during click and Diels-Alder (DA) reactions. We found that the diffusion coefficient of the reagents remained unchanged within the experimental uncertainty upon the DA reaction. Yet, diffusion of reagent molecules is faster than predicted during the click reaction when the reagent concentration and catalyst concentration exceed a threshold. A stepwise analysis suggested that the fast diffusion scenario is due to the reaction but not the involvement of the tracer with the reaction itself. The present results provide experimental evidence on the faster-than-expected reagent diffusion during a CuAAC reaction in specific conditions and propose new insights into understanding this unexpected behavior.

Impact of H2O on the Microscopic Oxidation Mechanism of Lollingite: Experimental and Theoretical Analyses.

Lollingite (FeAs2) is considered an arsenic-bearing mineral that is oxidized faster than arsenopyrite. The geometric configuration, chemical valence bond, and microscopic reaction of the oxidation on the surface of lollingite were systematically studied, which are of great significance for understanding the mechanism of oxidative dissolution. X-ray photoelectron spectroscopy (XPS) measurements and density functional theory (DFT) calculations were carried out to characterize the (101) surface oxidation process of lollingite under the O2/O2 + H2O conditions. XPS results confirmed that the participation of water molecules can promote the formation of abundant OH structures on the surface of lollingite, while the relative concentration of O, As(III), and Fe(III) increased. Moreover, the DFT results demonstrated that the (101) As-terminal plane of FeAs2 was the most stable surface with the lowest surface energy. H2O molecules were physically adsorbed onto the Fe atoms of the lollingite surface, while oxygen molecules can readily be adsorbed on the Fe-As2 site by chemical adsorption processes. The oxidation process of the lollingite surface with water includes the following mechanisms: adsorption, dissociation, formation of the hydrogen bond, and desorption. The dissociation of the H2O molecule into OH and H led to the hydroxylation of both Fe and As atoms and the formation of hydrogen bonding. The participation of H2O molecules can also reduce the reaction energy barrier and accelerate the oxidation reaction of the lollingite surface, especially as far as the water dissociation and formation of hydrogen bonds are concerned. According to PDOS data, there is considerable hybridization between the d orbitals of bonded Fe atoms and the p orbitals of O atoms, as well as between the p orbitals of bonded As atoms and the p orbitals of O atoms. Due to a strong propensity for orbital hybridization and bonding between the s orbitals of the H atoms in H2O molecules and the p orbitals of the O atoms on the (101) surface, water molecules have the ability to speed up the oxidation on the surface.

Investigation of SnS2 -rGO Sandwich Structures as Negative Electrode for Sodium-Ion and Potassium-Ion Batteries.

Sodium-ion and potassium-ion batteries (NIBs and KIBs) are considered promising alternatives to replace lithium-ion batteries (LIBs) in energy storage applications due to the natural abundance and low cost of Na and K. Nevertheless, a critical challenge is that the large size of Na+ /K+ leads to a huge volume change of the hosting material during electrochemical cycling, resulting in rapid capacity decay. Among negative candidates for alkali-metal-ion batteries, SnS2 is attractive due to the competitively high specific capacity, low redox potential and high abundance. Porous few-layer SnS2 nanosheets are in situ grown on reduced graphene oxide, forming a SnS2 -rGO sandwich structure via strong C-O-Sn bonds. This nano-scaled sandwich structure not only shortens Na+ /K+ and electron transport pathways but also accommodates volume expansion, thereby enabling high and stable electrochemical cycling performance of SnS2 -rGO. This work explores the influence of different conductive carbons (Super P and C65) on the SnS2 -rGO electrode. In addition, the effects of the electrolyte additive fluoroethylene carbonate (FEC) on the electrochemical performance in NIBs and KIBs is evaluated. This work provides guidelines for optimized electrode structure design, electrolyte additives and carbon additives for the realization of better NIBs and KIBs.

Multispectral camouflage nanostructure design based on a particle swarm optimization algorithm for color camouflage, infrared camouflage, laser stealth, and heat dissipation.

With the development of camouflage technology, single camouflage technology can no longer adapt to existing environments, and multispectral camouflage has attracted much research focus. However, achieving camouflage compatibility across different bands remains challenging. This study proposes a multispectral camouflage metamaterial structure using a particle swarm optimization algorithm, which exhibits multifunctional compatibility in the visible and infrared bands. In the visible band, the light absorption rate of the metamaterial structure exceeds 90%. In addition, color camouflage can be achieved by modifying the top cylindrical nanostructure to display different colors. In the infrared band, the metamaterial structure can achieve three functions: dual-band infrared camouflage (3-5 µm and 8-14 µm), laser stealth (1.06, 1.55, and 10.6 µm), and heat dissipation (5-8 µm). This structure exhibits lower emissivity in both the 3-5-µm (ɛ=0.18) and 8-14-µm (ɛ=0.27) bands, effectively reducing the emissivity in the atmospheric window band. The structure has an absorption rate of 99.7%, 95.5%, and 95% for 1.06, 1.55, and 10.6 µm laser wavelengths, respectively. Owing to its high absorptivity, laser stealth is achieved. Simultaneously, considering the heat dissipation requirements of metamaterial structures, the structural emissivity is 0.7 in the non-atmospheric window (5-8 µm), and the heat can be dissipated through air convection. Therefore, the designed metamaterial structure can be used in military camouflage and industrial applications.

Harmless Treatment of High Arsenic Tin Tailings and Environmental Durability Assessment.

The treatment of arsenic (As) in tin tailings (TT) has been an urgent environmental problem, and stabilization/solidification (S/S) treatment is considered an effective technology to eliminate contamination of As. In this study, we developed a low-carbon and low-alkalinity material to S/S of As, and the results showed that the leaching concentration of As after treatment was lower than the Chinese soil environmental quality standard (0.1 mg/L). Based on a series of characterization tests, we found that OH- promoted the dissolution of As(III)-S, Fe-As(V), and amorphous As(III)-O species and formed Ca-As(III) and Ca-(V) species with Ca2+. Simultaneously, hydration produces calcium silicate hydrate (C-S-H) gel and ettringite by the form of adsorption and ion exchange to achieve S/S of As. We also assessed the durability of this material to acidity and temperature, and showed that the leaching concentration of As was below 0.1 mg/L at pH = 1-5 and temperature 20-60 °C. The method proposed in this study, S/S of As, has excellent effect and environmental durability, providing a new solution for harmless treatment of TT and its practical application.

Registered Clinical Trials Comprising Pregnant Women in China: A Cross-Sectional Study.

Background: In this study, an investigation was conducted on clinical drug trials comprising pregnant women in China that provided data on the quantity, properties, source of funding, and geographical distribution regarding registration and post-marketing studies. Methods: We conducted a cross-sectional descriptive study of clinical trials of pregnant women in China on 30 December 2021, and it was registered on the official Drug Clinical Trial Information Management Platform (ChiCTR) (http://www.chinadrugtrials.org.cn) established by the State Food and Drug Administration of China (Chinese FDA). Results: This study encompassed 72 registered trials (0.46%, 72/15,539) for data analysis. Of these trials, 43.1% of trials were started between 2013 and 2016, and nearly half of the trials (48.6%) were completed. Industries were listed as the primary sponsor for 95.8% trials. Economically developed eastern China and northern China, accounting for 69.5% of the 72 registered trials, were the most frequently identified study locations. Regarding study designs of these trials, more than half of the trials (70.8%) were randomized, 61.1% were a parallel assignment, 33.3% were phase 3, and half of the trials (54.2%) were open label. In total, 23 trials met the requirements after excluding trials of cancer and/or of postmenopausal women, accounting for 0.15% of the 15,539 registered trials in the ChiCTR websites. Of the 72 clinical trials, 54 drugs for 18 indications were included. Of these indications, the highest proportion of the trials is osteoporosis (27.8%), followed by cancer (22.2%), assisted reproduction (13.9%), and other indications (13.9%). Conclusion: This survey revealed a significant shortage of the development, evaluation, and safety trials of pregnancy-related drugs in China. Modifying or adding legislation and providing financial incentives may therefore encourage pharmaceutical companies to conduct additional clinical trials on pregnant women.

Manipulating the Water Dissociation Electrocatalytic Sites of Bimetallic Nickel-Based Alloys for Highly Efficient Alkaline Hydrogen Evolution.

Transition-metal alloys are currently drawing increasing attention as promising electrocatalysts for the alkaline hydrogen evolution reaction (HER). However, traditional density-functional-theory-derived d-band theory fails to describe the hydrogen adsorption energy (ΔGH ) on hollow sites. Herein, by studying the ΔGH for a series of Ni-M (M=Ti, V, Cr, Mn, Fe, Co, Cu, Zn, Mo, W) bimetallic alloys, an improved d-band center was provided and a potential NiCu electrocatalyst with a near-optimal ΔGH was discovered. Moreover, oxygen atoms were introduced into Ni-M (O-NiM) to balance the adsorption/desorption of hydroxyl species. The tailored electrocatalytic sites for water dissociation can synergistically accelerate the multi-step alkaline HER. The prepared O-NiCu shows the optimum HER activity with a low overpotential of 23 mV at 10 mA cm-2 . This work not only broadens the applicability of d-band theory, but also provides crucial understanding for designing efficient HER electrocatalysts.

Microstructure and Phase Evolution Characteristics of the In Situ Synthesis of TiC-Reinforced AZ91D Magnesium Matrix Composites.

TiC-reinforced AZ91D magnesium alloy composites were synthesized through the in situ reaction between an AZ91D melt and Ti-C-Al preforms. The microstructural evolution characteristics and phase transformation were investigated at different melt reaction temperatures (1013, 1033, and 1053 K), with the aim of understanding the in situ formation mechanism of TiC particles from thermodynamic and kinetic perspectives. The results showed that the temperature played a critical role in determining the formation and morphology of TiC. Initially, only the Al3Ti phase was formed through the reaction between Ti and Al when the temperature was 1013 K. With the increase in the melt temperature, the A13Ti's thermodynamic stability decreased, and dissolution and precipitation reactions occurred at higher temperatures (1033 and 1053 K, respectively), contributing to the formation of TiC particles. The formation of the TiC phase was attributed to two factors: Firstly, A13Ti as an intermediate product reacted with carbon and formed TiC with increasing temperature. Secondly, the in situ TiC reaction was promoted due to the increased reaction-driving force provided by the increasing temperature.

Correlation between frail status and lower extremity function in elderly inpatients with hypertension.

INTRODUCTION: Introduction: the frail status of elderly hypertensive patients easily damages the function of many physiological systems. Objectives: we aimed to investigate the correlation between the frail status and lower extremity function of elderly hospitalized patients with hypertension. Methods: a total of 336 eligible subjects were assigned to frail, pre-frail and non-frail groups according to the "Frail" scale. Lower extremity function was assessed by the Short Physical Performance Battery including chair-sit-to-stand, three-posture balance and 6-meter gait speed tests. The influences of factors on frailty were evaluated using the Cox multivariate regression analysis. The correlation between frailty score and lower extremity function score was explored by Spearman's analysis. The values of factors for predicting frail status were analyzed by plotting receiver operating characteristic (ROC) curves. Results: the three groups had similar age, systolic blood pressure, and nutritional, sleepiness and lower extremity function statuses (p < 0.05). Compared with the non-frail group, the lower extremity function score of the frail group was lower (p < 0.05). Age, systolic blood pressure and sleepiness status were the independent risk factors of frailty (p < 0.05), and lower extremity function parameters were independent protective factors (p < 0.05). There were negative correlations between frail status and lower extremity function parameters (p < 0.05). The area under the ROC curve was 0.850, and the optimal cutoff value was 7.80. Lower extremity function had a high value for predicting frail status. Conclusions: lower extremity function is negatively correlated with the frail status of elderly hospitalized patients with hypertension, as a protective factor of frailty, which can be used to predict frail status.

INTRODUCCIÓN: Introducción: el estado frágil de los pacientes hipertensos de edad avanzada daña fácilmente la función de muchos sistemas fisiológicos. Objetivos: nuestro objetivo fue investigar la correlación entre el estado frágil y la función muscular de pacientes ancianos hospitalizados con hipertensión. Métodos: un total de 336 sujetos elegibles fueron asignados a grupos de frágiles, pre-frágiles y no frágiles de acuerdo con la escala de fragilidad. La función muscular se evaluó mediante la batería de rendimiento físico corto, que incluye las pruebas de sentarse y levantarse de una silla, equilibrio de tres posturas y velocidad de marcha de 6 metros. Las influencias de los factores sobre la fragilidad se evaluaron mediante el análisis de regresión multivariante de Cox. La correlación entre el puntaje de fragilidad y el puntaje de función muscular se exploró con el análisis de Spearman. Los valores de los factores para predecir el estado frágil se analizaron mediante el trazado de curvas características de funcionamiento del receptor (ROC). Resultados: los tres grupos tenían edades similares y valores similares de presión arterial sistólica y estado nutricional, somnolencia y función muscular (p < 0,05). En comparación con el grupo no frágil, la puntuación de la función muscular del grupo frágil fue menor (p < 0,05). La edad, la presión arterial sistólica y el estado de somnolencia fueron los factores de riesgo independientes de fragilidad (p < 0,05), y los parámetros de función muscular fueron factores protectores independientes (p < 0,05). Hubo correlaciones negativas entre el estado frágil y los parámetros de la función muscular (p < 0,05). El área bajo la curva ROC fue de 0,850 y el valor de corte óptimo fue de 7,80. La función muscular tuvo un valor alto para predecir el estado frágil. Conclusiones: la función muscular se correlaciona negativamente con el estado frágil de los pacientes ancianos hospitalizados con hipertensión, como factor protector de la fragilidad, que se puede utilizar para predecir el estado frágil.

Red mud-metakaolin based cementitious material for remediation of arsenic pollution: Stabilization mechanism and leaching behavior of arsenic in lollingite.

The proper treatment of lollingite is of great significance due to its rapid oxidation leading to release of arsenic into the environment. Herein, a green multi-solid waste geopolymer, consisting of red mud, metakaolin, blast furnace slag, and flue gas desulfurization gypsum, was developed. The obtained red mud-metakaolin-based (RMM) geopolymer demonstrated good arsenic retention capability. The results showed that the replacement of SO42- in ettringite with AsO42- via ion exchange, formation of Ca-As and Fe-As precipitates, and physical encapsulation with aluminosilicate gel were the main mechanisms that prevented the release of arsenic. Further dissolution of ettringite in RMM was alleviated by adding a suitable amount of Ca(OH)2 and controlling the pH of the leachate. TCLP results verified that RMM materials possessed an outstanding ability to stabilize arsenic, with a leaching rate below the permitted value of 5 mg/L for safe disposal. The low leachability of the RMM geopolymers (<0.50 mg/L) is potentially related to the pH buffering capacity of the hydration products at a pH range of 2-5. RMM geopolymers showed a high compressive strength (>15 MPa) and low arsenic leaching concentration (<2.66 mg/L) after 28 days of curing. These results demonstrate the potential of RMM geopolymers to be utilized as an environmentally friendly backfilling cementitious material for sustainable remediation of arsenic pollution.

High thermoelectric performance of half-Heusler ZrXPb (X= Ni, Pd, and Pt) compounds from first principle calculation.

Half-Heusler compounds have distinguished themselves as outstanding thermoelectric materials on account of high temperature stability and large thermopower. However, the dimensionless figure of merit of traditional half-Heusler alloys remains low. In this study, we investigate the thermoelectric performance of novel ZrXPb (X= Ni, Pd, and Pt) ternary compounds by semi-classical Boltzmann transport theory combining with deformation potential. The n-type ZrNiPb and ZrPtPb exhibits obviously largeZTvalues of 1.71 around 650 K and 1.75 around 1200 K, with 1.17 × 1020 cm-3and 3.43 × 1020 cm-3, respectively. The electron and phonon structure calculations demonstrate that for the n-type ZrXPb (X= Ni, Pd, and Pt) compounds, doping at Pb site can not only modify the carrier concentrations but also significantly decrease the lattice thermal conductivity. These investigations are expected to be beneficial to the exploration of novel highZTthermoelectric materials.

Automatic Facial Recognition of Williams-Beuren Syndrome Based on Deep Convolutional Neural Networks.

Background: Williams-Beuren syndrome (WBS) is a rare genetic syndrome with a characteristic "elfin" facial gestalt. The "elfin" facial characteristics include a broad forehead, periorbital puffiness, flat nasal bridge, short upturned nose, wide mouth, thick lips, and pointed chin. Recently, deep convolutional neural networks (CNNs) have been successfully applied to facial recognition for diagnosing genetic syndromes. However, there is little research on WBS facial recognition using deep CNNs. Objective: The purpose of this study was to construct an automatic facial recognition model for WBS diagnosis based on deep CNNs. Methods: The study enrolled 104 WBS children, 91 cases with other genetic syndromes, and 145 healthy children. The photo dataset used only one frontal facial photo from each participant. Five face recognition frameworks for WBS were constructed by adopting the VGG-16, VGG-19, ResNet-18, ResNet-34, and MobileNet-V2 architectures, respectively. ImageNet transfer learning was used to avoid over-fitting. The classification performance of the facial recognition models was assessed by five-fold cross validation, and comparison with human experts was performed. Results: The five face recognition frameworks for WBS were constructed. The VGG-19 model achieved the best performance. The accuracy, precision, recall, F1 score, and area under curve (AUC) of the VGG-19 model were 92.7 ± 1.3%, 94.0 ± 5.6%, 81.7 ± 3.6%, 87.2 ± 2.0%, and 89.6 ± 1.3%, respectively. The highest accuracy, precision, recall, F1 score, and AUC of human experts were 82.1, 65.9, 85.6, 74.5, and 83.0%, respectively. The AUCs of each human expert were inferior to the AUCs of the VGG-16 (88.6 ± 3.5%), VGG-19 (89.6 ± 1.3%), ResNet-18 (83.6 ± 8.2%), and ResNet-34 (86.3 ± 4.9%) models. Conclusions: This study highlighted the possibility of using deep CNNs for diagnosing WBS in clinical practice. The facial recognition framework based on VGG-19 could play a prominent role in WBS diagnosis. Transfer learning technology can help to construct facial recognition models of genetic syndromes with small-scale datasets.

Erratum: miR-26b inhibits isoproterenol-induced cardiac fibrosis via the Keap1/Nrf2 signaling pathway.

[This corrects the article DOI: 10.3892/etm.2020.8455.].

miR-26b inhibits isoproterenol-induced cardiac fibrosis via the Keap1/Nrf2 signaling pathway.

A critical event in cardiac fibrosis is the transformation of cardiac fibroblasts (CFs) into myofibroblasts. MicroRNAs (miRNAs) have been reported to be critical regulators in the development of cardiac fibrosis. However, the underlying molecular mechanisms of action of miRNA (miR)-26b in cardiac fibrosis have not yet been extensively studied. In the present study, the expression levels of miR-26b were downregulated in isoproterenol (ISO)-treated cardiac tissues and CFs. Moreover, miR-26b overexpression inhibited the cell viability of ISO-treated CFs and decreased the protein levels of collagen I and α-smooth muscle actin (α-SMA). Furthermore, bioinformatics analysis and dual luciferase reporter assays indicated that Kelch-like ECH-associated protein 1 (Keap1) was the target of miR-26b, and that its expression levels were decreased in miR-26b-treated cells. In addition, Keap1 overexpression reversed the inhibitory effects of miR-26b on ISO-induced cardiac fibrosis, as demonstrated by cell viability, and the upregulation of collagen I and α-SMA expression levels. Furthermore, inhibition of Keap1 expression led to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which induced the transcriptional activation of antioxidant/detoxifying proteins in order to protect against cardiac fibrosis. Taken together, the data demonstrated that miR-26b attenuated ISO-induced cardiac fibrosis via the Keap-mediated activation of Nrf2.