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Casper/c-FLIP is a caspase-8-related molecule critically involved in regulation of death receptor-induced apoptosis. It has been shown that Casper can either promote or antagonize apoptosis and can activate the transcription factor NF-κB. The exact functions of Casper are controversial. To further understand how Casper signals, we searched Casper-interacting proteins by yeast two-hybrid screening. This effort identified NF-κB1 (p105), an atypical IκB molecule and the precursor of NF-κB subunit p50. Co-immunoprecipitation experiments indicated that Casper interacted with p105 in 293 cells and this interaction was mediated through the C-terminal IκB-like domain (IκBγ). Overexpression of p105 and IκBγ inhibited Casper-induced NF-κB activation and potentiated Casper-induced apoptosis. Furthermore, Casper and its C-terminal caspase-like domain inhibited p105 processing into p50. Our findings suggest that p105 is involved in Casper-mediated regulation of apoptosis and NF-κB activation. [Copyright &y& Elsevier]

[Display omitted] • Kohistan and Gangdese (garnet) hornblendites and/or garnet gabbros are of cumulate origins. • Amphiboles in these lower crust cumulates have high Nb/Ta but low Nb and Ta concentrations. • Amphibole fractionation will not change Nb/Ta ratio of arc magmas significantly. • Rutile likely plays an important role in Nb/Ta fractionation in continental crust formation. Earth's continental crust has a lower Nb/Ta ratio than that of its building blocks –basaltic melts from the mantle. This Nb/Ta mass imbalance implies the existence of a complementary high Nb/Ta reservoir in deep crust. Amphibole-rich arc cumulates have been proposed to be one such candidate due to the preferential partitioning of Nb over Ta into amphibole. To test this proposal, we carried out in-situ analyses of amphibole and rutile in the lower crustal rocks from Kohistan arc and Gangdese arc. Petrological observations and geochemical results suggest that these rocks in both Kohistan arc and Gangdese arc are of magmatic origins and formed by crystal accumulation, i.e. of cumulate. The Kohistan garnet-bearing hornblendite cumulates were formed at 952–1009 ℃; the garnet-free hornblendite cumulates in Kohistan arc and Gangdese arc were formed at 941–992 ℃ and 955–1027 ℃, respectively. We find that, although the amphibole of the Kohistan and Gangdese cumulates have high Nb/Ta ratios (average 18.2 and 17.0, respectively), their Nb and Ta concentrations are far lower than mantle-derived volcanics (Nb < 1.1 ppm, Ta < 0.11 ppm). We show that, with such low concentrations of Nb and Ta, amphibole fractionation will not change arc magma Nb/Ta ratios significantly. Instead, the rutile in Kohistan cumulates has high Nb/Ta ratios and high Nb-Ta concentrations. The calculation shows that rutile may play a more important role in Nb/Ta fractionation during arc magma differentiation in thickened arc crust. Our study provides a mineralogical perspective to understand the formation of continental crust, and improves our understanding how Nb or Ta becomes enriched in arc setting. [ABSTRACT FROM AUTHOR]

A heterostructured Co-based electrocatalyst is successfully synthesized using bifunctional ligand Co metal–organic frameworks as precursors. The bifunctional ligands provide enough N and O atoms that can simultaneously convert Co ions into CoN x moieties, Co nanoparticles and Co oxides via one-step pyrolysis. The obtained electrocatalysts with heterostructured CoO x /Co nanoparticles encapsulated by porous conductive carbon rich in CoN x active sites deliver remarkable oxygen reduction reaction and oxygen evolution reaction activities. With the synergistic effects among these multifunctional components, a rechargeable zinc–air battery built with this electrocatalyst exhibits a high-power density and long-lasting rechargeability. [Display omitted] Rational construction of efficient and robust bifunctional oxygen electrocatalysts is key but challenging for the widespread application of rechargeable zinc-air batteries (ZABs). Herein, bifunctional ligand Co metal–organic frameworks were first explored to fabricate a hybrid of heterostructured CoO x /Co nanoparticles anchored on a carbon substrate rich in CoN x sites (CoO x /Co@Co N C) via a one-step pyrolysis method. Such a unique heterostructure provides abundant CoN x and CoO x /Co active sites to drive oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), respectively. Besides, their positive synergies facilitate electron transfer and optimize charge/mass transportation. Consequently, the obtained CoO x /Co@Co N C exhibits a superior ORR activity with a higher half-wave potential of 0.88 V than Pt/C (0.83 V vs. RHE), and a comparable OER performance with an overpotential of 346 mV at 10 mA cm−2 to the commercial RuO 2. The assembled ZAB using CoO x /Co@Co N C as a cathode catalyst displays a maximum power density of 168.4 mW cm−2, and excellent charge–discharge cyclability over 250 h at 5 mA cm−2. This work highlights the great potential of heterostructures in oxygen electrocatalysis and provides a new pathway for designing efficient bifunctional oxygen catalysts toward rechargeable ZABs. [ABSTRACT FROM AUTHOR]

The genomic landscape of metastatic renal cell carcinoma (RCC) is not well understood, and currently available data suggest that it is functionally distinct from that of localized tumors. Additionally, the large number of approved and trial agents used to treat metastatic RCC likely cause selective adaptations in the tumors. Circulating tumor DNA (ctDNA) is a platform to non-invasively determine the genomic profiles of these tumors. The objectives of the present study were to corroborate previous ctDNA studies in metastatic RCC, to identify novel mutations in metastatic RCC, and to compare ctDNA profiles obtained from plasma and urine in patients with metastatic RCC. ctDNA sequencing using the plasma and urine of 50 patients with metastatic RCC who received ctDNA profiling as part of routine clinical care at a single institution was performed using an investigational 120-gene panel. Genomic alterations (GAs) were identified in all 50 patients. The genes with the most GAs were GNAS, PTEN, MYC, MET and HNF1A and novel mutations in additional genes were identified. A significant correlation between the number of GAs detected in matched urine and plasma samples was also identified, but only 28.1% of GAs detected in plasma samples were also detected in matched urine samples. The results of the present study were consistent with those of the largest previous study of ctDNA from patients with metastatic RCC and may help identify additional potential targets for the treatment of such patients. [ABSTRACT FROM AUTHOR]

Endometrial carcinoma (EC), an estrogen-dependent gynecological malignancy, is prevalent worldwide. Estrogen receptor α (ERα) and estrogen receptor β (ERβ) are two main estrogen receptor isoforms, which mediate estrogen-induced proliferation in EC. However, the dynamic changes of ERα and ERβ subtype expression and their functions on proliferation in EC remain elusive. In this study, we aimed to investigate the expression of ERα and ERβ in para-tumor eutopic endometrium, endometrial atypical hyperplasia and EC by immunohistochemistry and then analyse their clinical significance. Subsequently, Ishikawa cells with ERα or ERβ knockdown by lentivirus transfection were used to explore the relationship between ERα/ERβ and cell proliferation, and preliminarily evaluate whether metformin's inhibitory effect on estrogen-induced cell proliferation was mediated by ERα and ERβ. We found that the expression of ERα and ERβ were markedly changed in endometrial hyperplasia and EC compared with that in para-tumor eutopic endometrium and exhibited different expression trends. Through further analysis, we discovered that ERα presented higher expression in endometrial atypical hyperplasia and early stage of EC than that in para-tumor eutopic endometrium, while the expression of ERβ gradually decreased from para-tumor eutopic endometrium to EC. Additionally, the cell cycle-related protein, CyclinD1 was gradually increased but p21 decreased. Furthermore, knockdown of ERα and ERβ severally in Ishikawa cells either inhibited or promoted estrogen-induced cell proliferation through regulating CyclinD1 and p21 expression. Meanwhile, the inhibitory effect of metformin on estrogen-induced cell proliferation was respectively blunted or partly reversed by knockdown of ERα or ERβ. Altogether, ERα and ERβ have different expression patterns in the progression of EC either facilitating or suppressing cell proliferation through regulating the expression of CyclinD1 and p21 in EC cells, and may also mediate the inhibitory effect of metformin on estrogen-induced EC cells proliferation. [ABSTRACT FROM AUTHOR]

Three strains of lactic acid bacteria (LAB), including two strains of Lactobacillus plantarum and one strain of Lactococcus lactis isolated from spontaneously fermented Yucha, a traditional Chinese home-made fermented fish product, were evaluated as starter cultures for Yucha production. All three starter cultures could drive Yucha fermentation processes by rapid colonizing and fast acidifying the raw fish materials, and restricting the growth of undesirable bacteria. As a result, the starter-inoculated Yucha products were safer than their spontaneously-fermented counterpart, and fewer biogenic amines were detected in them. During the late stage of Yucha fermentation, the initial L. lactis was gradually replaced by endogenous L. plantarum , indicating that Yucha environmental condition is a favorable niche of L. plantarum. Volatile compounds profiling combined with cluster analysis demonstrated that the competition between the two species significantly shaped the development of aroma and flavor compounds in Yucha. Besides, correlation analysis suggested that 1-methyl-naphthalene could be a potential indicator to evaluate the degree of ripeness in Yucha products. • Three starter cultures could all accelerate Yucha fermentation process. • The inoculated Yucha products were safer than their spontaneous counterparts. • The starter L. lactis was replaced by L. plantarum at the end of fermentation. • The interaction between bacteria greatly shaped volatiles profiles of Yucha. • 1-methyl-naphthalene could be an indicator to predict the maturity of Yucha. [ABSTRACT FROM AUTHOR]

• Tulasu porphyries have favorable oxygen fugacity but don't have enough magmatic water content. • Tulasu porphyries have suitable crustal thickness, which are both >30 km. • Tulasu porphyries have low potential in forming porphyry Cu deposits. Tulasu basin in Northwest Tianshan hosts a lot of Late Paleozoic epithermal deposits, such as Axi, Jingxi-Yelmand, and Tawuerbieke deposits. Epithermal deposits are considered as telescoped systems of porphyry deposits. However, porphyry deposits are not discovered in Tulasu basin, though granitoid porphyries are widespread in this region. Tulasu pluton complex, as one of the largest intrusions located in northeast part of Tulasu basin, is composed of the Late Devonian quartz diorite porphyry and pyroxene diorite porphyry, and the Late Carboniferous granodiorite porphyry and granite porphyry. The metallogenic potential of each rock type is evaluated in terms of magma nature and crustal thickness of source. The magma nature including magmatic oxygen fugacity and water content is estimated based on trace elements compositions of zircons, amphibole hygro-barometer and ilmenite-magnetite mineral pairs. The mean Ce4+/Ce3+ ratio, magmatic oxygen fugacity and water content of the Late Devonian quartz diorite porphyry are 291, ΔFMQ = 1.0–1.8, ΔFMQ = −0.2–1.5 and 0.9–2.2 wt%, respectively, while those of pyroxene diorite porphyry are 96, ΔFMQ = 2.6–3.3 and 0.2–1.3 wt%. The Late Carboniferous granodiorite porphyry has a mean Ce4+/Ce3+ ratio of 138. The crustal thicknesses in the Tulasu area are estimated to be 30–35 km at the Late Devonian and ~40 km at the Late Carboniferous, based on whole rock geochemistry of the Late Devonian dioritic rocks and the Late Carboniferous granitic rocks. Considering magmas associated with typical porphyry deposits which have high oxygen fugacity of ΔFMQ = +1.5 to +3 and water content (>4.5 wt%), and are derived from crustal thickness of >30 km, we think both dioritic and granitic rocks of Tulasu porphyries have favorable conditions of oxidation state and crustal thickness for porphyry deposit formation. However, the magmatic water contents of these rocks are relatively low. Therefore, the Tulasu porphyries have low potential in forming porphyry Cu deposits. [ABSTRACT FROM AUTHOR]

Activated M1-type macrophages, which produce inflammatory factors that exacerbate rheumatoid arthritis (RA), represent crucial target cells for inhibiting the disease process. In this study, we developed a novel photoresponsive targeted drug delivery system (TPNPs-HA) that can effectively deliver the hypoxia-activated prodrug tirapazamine (TPZ) specifically to activated macrophages. After administration, this metal-organic framework, PCN-224, constructed uing the photosensitizer porphyrin, exhibits the ability to generate excessive toxic reactive oxygen species (ROS) when exposed to near-infrared light. Additionally, the oxygen-consumed hypoxic environment further activates the chemotherapeutic effect of TPZ, thus creating a synergistic combination of photodynamic therapy (PDT) and hypoxia-activated chemotherapy (HaCT) to promote the elimination of activated M1-type macrophages. The results highlight the significantly potential of this photoresponsive nano-delivery system in providing substantial relief for RA. Furthermore, these findings support its effectiveness in inhibiting the disease process of RA, thereby offering new possibilities for the development of precise and accurate strategies for RA. • A novel strategy for the combined treatment of RA with PDT and HaCT was proposed. • A new nanosized PCN-224 was constructed as multifunctional vehicle for drug delivery. • MOF binds HA as a targeting molecule to activated macrophages through its own positive electrical properties. [ABSTRACT FROM AUTHOR]

We introduce a passive tomography method with deep field of view up to 90 m based on the self-acceleration characteristics of Airy beams. A post-modulation long-distance imaging system was proposed and optimized in its optical configuration and phase modulation parameters. The resolution was analyzed based on theoretical simulation. Experimentally, three LEDs at various distances around 10 m and two outdoor road lamps with distance of 67 and 90 m were reconstructed using the Airy-beam tomography algorithm, respectively, demonstrating excellent tomographic characteristics. This work presents a feasible candidate for the 3D passive detection for long-distance targets. [ABSTRACT FROM AUTHOR]

Molybdenum disulfide (MoS2) is a promising anode material for lithium-ion batteries (LIBs) due to its distinctive graphene-like structure and high specific capacity. However, its commercial application is hindered by the severe volume expansion during lithiation/delithiation and poor conductivity. In this paper, we report a facile one-pot enhanced hydrothermal synthesis strategy to prepare high-performance MoS2/C composite materials. The results indicate that the as-prepared MoS2/C composite is a subspheroidal core–shell structure material, with uniform coating, good particle dispersion, and an average grain size of approximately 80 nm. The morphology of the composite remained unchanged even after annealing at 500 °C for 2 h. The addition of glucose can accelerate the nucleation and growth of MoS2, and higher hydrothermal temperatures can improve the product yield. The addition of PVP has little effect on the yield, but significantly reduces the particle size. The XPS analysis reveals that the MoO3 may be generated as an intermediate product during the hydrothermal process. The electrochemical test results show that the unannealed MoS2/C samples exhibit discharge-specific capacities of 705.2 mAh·g−1 and 625.7 mAh·g−1 after the first cycle and the 100th cycle, respectively, at a current density of 500 mA·g−1, with a capacity retention rate of 88.7%. In contrast, the specific capacity of the MoS2/C specimens after annealing at 500 °C for 2 h shows a tendency to decrease and then slowly increase during the cycles, and the discharge specific capacity is 582.3 mAh·g−1 after the 100th cycle, which is lower than that of the unheated sample. The impedance analysis reveals that the lithium-ion diffusion coefficient of the MoS2/C material without calcination is 2.11 × 10−18 cm·s−2, which is superior to that of the annealed MoS2/C and pristine MoS2 samples. This characteristic is favorable for lithiation/delithiation during the charge/discharge process. [ABSTRACT FROM AUTHOR]

To investigate the anti-inflammatory actions and molecular mechanisms of the sodium/glucose cotransporter 2 (SGLT-2) inhibitor empagliflozin on autoimmune myocarditis. The experimental autoimmune myocarditis (EAM) mouse model was constructed using peptides, and the therapeutic effects of empagliflozin on cardiac inflammation and fibrosis were observed using hematoxylin and eosin (HE), Sirius red staining, and Masson's trichome staining. Western blotting was used to identify the actions of empagliflozin on the surface marker expression levels of M2 macrophages and inflammatory factors. In vitro, experiments were completed using lentiviral overexpression of SGLT-2 in macrophages. Macrophage inflammation and anti-inflammatory models were constructed using lipopolysaccharide and interleukin-4, respectively. Enzyme-linked immunosorbent assay, immunofluorescence staining, and reverse-transcription polymerase chain reaction were applied to detect the effects of empagliflozin on the levels of inflammatory factors and macrophage surface markers. Western blotting was used to identify variability in SGLT-2 expression and the role of empagliflozin on the signal transducer and activator of the transcription 3 (STAT3) pathway. The Genomic Spatial Event 142564 dataset was studied in an EAM mouse model. We selected single-cell sequencing results from day 0 and day 21 of modeling to visualize differentially expressed genes. Immune cell infiltration correlation analysis was implemented to explore the expression of inflammatory factors and phenotypic markers. Empagliflozin increased the expression of the M2 macrophage surface marker CD206 and reduced the level of inflammatory factors in the EAM mouse model while reducing the levels of inflammation and fibrosis. In vitro experiments revealed that the phosphorylation of STAT3 pathway was enhanced after macrophages were polarized to M1 phenotype by LPS, the phosphorylation of STAT3 pathway was inhibited after empagliflozin intervention, and the levels of inflammatory factors were decreased. Empagliflozin can reduce the level of inflammation in autoimmune myocarditis through the STAT3 pathway and macrophage phenotype transformation. These results indicate the expression of SGLT-2 can be a target for autoimmune myocarditis therapy. • An autoimmune myocarditis mouse model using scRNA-seq data was analysed. • Lentiviral overexpression of SGLT-2 was also performed in vitro in macrophages. • Empagliflozin reduced the expression of inflammatory factors as well as fibrosis. • STAT3 pathway phosphorylation was inhibited by empagliflozin administration. [ABSTRACT FROM AUTHOR]

Background/Aims: Sinomenine, a pure alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, and sinomenine hydrochloride (SN) has been successfully used for the therapy of rheumatoid arthritis (RA) and kidney diseases. Autophagy is a cytoprotective mechanism used by podocytes and other cells to alleviate the effects of oxidative stress, and angiotensin II (Ang II) significantly promotes podocyte autophagy. However, excessive autophagy may lead to cell death and podocyte depletion. The present study evaluated the effect of SN in podocytes induced by Ang II. Methods: Podocytes were pretreated with graded concentrations (10-8 M ∼ 10-4 M) of SN and then stimulated with Ang II. The LC3B protein and the p47-phox membrane fraction were measured by Western blot. Autolysosomes were assessed by transmission electron microscopy. FACS was used to quantify the ROS produced by podocytes. The translocation of p47-phox to the membrane was investigated by immunofluorescence. Results: The 10-8 M ∼ 10-4 M of SN alone did not effect ROS generation or podocyte autophagy. The 10-8 M and 10-6 M SN attenuated Ang II-induced autophagy in podocytes. Furthermore, SN decreased the level of ROS generation in Ang II-induced podocytes via inhibition of NOX subunit p47-phox translocation to the membrane. Conclusion: The appropriate concentration of SN attenuated Ang II-induced podocyte autophagy through ROS generation, at least in part, by regulating NOX subunit p47-phox translocation to the membrane. [ABSTRACT FROM AUTHOR]

Strongly intensive quantities Σ[ P T , N ] and Δ[ P T , N ] have become one of the important tools in study of phase transitions and critical points in high energy heavy-ion collisions. In this paper the properties of Σ[ P T , N ] and Δ[ P T , N ] are discussed within different colliding nuclei systems generated by the AMPT model. The combined event method are proposed to simulate the model of independent sources in which Σ[ P T , N ] and Δ[ P T , N ] are independent of the number of original events. The effects of transverse momentum, pseudorapidity and parton cascade are also discussed. [ABSTRACT FROM AUTHOR]

Background: Nitraria tangutorum is an important desert shrub that shows resistance to drought, salt and wind erosion stresses. It is a central ecological species in its area. Here, we have studied how N. tangutorum has adapted to achieve a successful reproduction strategy. Results: We found that N. tangutorum is mainly pollinated by insects of the Hymenoptera, Diptera and Coleoptera orders. Nitraria tangutorum has very small flowers, with the nectary composed of secretive epidermal cells from which nectar is secreted, located within the inner petals. In addition, analyzing the transcriptome of four successive flower developmental stages revealed that mainly differentially expressed genes associated with flower and nectary development, nectar biosynthesis and secretion, flavonoid biosynthesis, plant hormone signal transduction and plant-pathogen interaction show dynamic expression. From the nectar, we could identify seven important proteins, of which the L-ascorbate oxidase protein was first found in plant nectar. Based on the physiological functions of these proteins, we predict that floral nectar proteins of N. tangutorum play an important role in defending against microbial infestation and scavenging active oxygen. Conclusions: This study revealed that N. tangutorum is an insect-pollinated plant and its nectary is composed of secretive epidermal cells that specialized into secretive trichomes. We identified a large number of differentially expressed genes controlling flower and nectary development, nectar biosynthesis and secretion, flavonoid biosynthesis, plant hormone signal transduction and plant-pathogen interaction. We suggest that proteins present in N. tangutorum nectar may have both an antibacterial and oxygen scavenging effect. These results provide a scientific basis for exploring how the reproductive system of N. tangutorum and other arid-desert plants functions. [ABSTRACT FROM AUTHOR]

Background: Guard cells perceive external and internal stimuli and regulate stomatal conductance in plants. With the use of gas exchange analyzers, time-resolved stomatal conductance responses to light intensity, [CO2] concentration and relative humidity changes can be measured. This is more difficult to achieve when measuring stomatal responses to small soluble molecules such as the plant hormone abscisic acid (ABA) or the bacterial peptide flagellin 22 (flg22), in particular when investigating mutants with response phenotypes. Results: A method to evaluate the dynamic effects of small molecules on stomatal conductance in a time-resolved fashion using gas exchange analyzers is presented here. ABA-induced stomatal closure was investigated by adding ABA to the transpiration stream of intact leaves placed in a microcentrifuge tube containing water. Strong ABA responses were resolved in time- and in a dose-dependent manner in wild-type Arabidopsis leaves, whereas the same response was not observed in leaves of the ABA-insensitive mutant open stomata 1-3 (ost1-3). Moreover, when leaves of the Plasma membrane Intrinsic Protein (PIP) aquaporin quadruple mutant pip1;1 pip1;2 pip2;1 pip2;2 were tested, robust wild-type-like responses to ABA were observed. When the bacterial peptide flg22 was added to the transpiration stream of intact wild-type leaves, a strong flg22-induced stomatal closure effect was observed. Finally, the proposed technique was further developed and optimized for evaluation of stomatal conductance responses to small molecules in leaves of grasses using the reference plant Brachypodium distachyon. Conclusions: Due to the variable size of stomata in Arabidopsis and the limited dynamic response of stomata in isolated epidermal strips, evaluation of the effect of small molecules on stomatal physiology has been challenging and has led in some cases to inconsistent results. Moreover, potential signals from the mesophyll are missing when using epidermal peels to evaluate stomatal aperture responses. Here we propose a less invasive technique which allows for time-resolved measurements of stomatal conductance responses to small molecules optimized for both Arabidopsis and Brachypodium distachyon leaves. [ABSTRACT FROM AUTHOR]

Retinoid-related orphan receptor gamma t (RORγt) is the lineage-specific transcription factor for T helper 17 (Th17) cells. Our previous study demonstrated that STAT3 likely participates in the activation of RORCE2 (a novel enhancer of the RORγt gene) in Th17 cells. However, the detailed mechanism is still unclear. Here, we demonstrate that both STAT3 and SOX-5 mediate the enhancer activity of RORCE2 in vitro. Deletion of the STAT3 binding site (STAT3-BS) in RORCE2 impaired RORγt expression and Th17 differentiation, resulting in reduced severity of experimental autoimmune encephalomyelitis (EAE). Mechanistically, STAT3 and SOX-5 bind the RORCE2 region and recruit the chromatin remodeling factor BRG1 to remodel the nucleosomes positioned at this region. Collectively, our data suggest that STAT3 and SOX-5 mediate the differentiation of Th17 cells through the induction of BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells. STAT3 and SOX-5 may mediate Th17 cell differentiation through the induction of BRG1-mediated chromatin remodeling of RORCE2. [ABSTRACT FROM AUTHOR]

[Display omitted] Rechargeable zinc-air batteries (ZABs) with high energy density and low pollutant emissions are regarded as the promising energy storage and conversion devices. However, the sluggish kinetics and complex four-electron processes of oxygen reduction reaction and oxygen evolution reaction occurring at air electrodes in rechargeable ZABs pose significant challenges for their large-scale application. Carbon-supported single-atom catalysts (SACs) exhibit great potential in oxygen electrocatalysis, but needs to further improve their bifunctional electrocatalytic performance, which is highly related to the coordination environment of the active sites. As an extension of SACs, dual-sites SACs with wide combination of two active sites provide limitless opportunities to tailor coordination environment at the atomic level and improve catalytic performance. The review systematically summarizes recent achievements in the fabrication of dual-site SACs as bifunctional oxygen electrocatalysts, starting by illustrating the design fundament of the electrocatalysts according to their catalytic mechanisms. Subsequently, metal-nonmetal-atom synergies and dual-metal-atom synergies to synthesize dual-sites SACs toward enhancing rechargeable ZABs performance are overviewed. Finally, the perspectives and challenges for the development of dual-sites SACs are proposed, shedding light on the rational design of efficient bifunctional oxygen electrocatalysts for practical rechargeable ZABs. [ABSTRACT FROM AUTHOR]

Simple Summary: Machine learning methods have shown promise in accurately identifying small lung nodules. However, further exploration is needed to fully harness the potential of machine learning in distinguishing between benign and malignant nodules. This study aimed to develop and evaluate a ResNet50-Ensemble Voting model for detecting the nature (benign or malignant) of small pulmonary nodules (less than 20 mm) based on CT images. This study involved 834 CT imaging data from 396 patients with small pulmonary nodules. CT image features were extracted using ResNet50 and VGG16 algorithms, and classification was performed using XGBoost, SVM, and Ensemble Voting techniques, incorporating ten different combinations of machine learning classifiers. Among the models tested, the ResNet50-Ensemble Voting algorithm demonstrated the highest performance in the test set, achieving an accuracy of 0.943 (0.938, 0.948), with sensitivity and specificity values of 0.964 and 0.911, respectively. The implementation of machine learning models, particularly the ResNet50-Ensemble Voting approach, showed excellent performance in accurately identifying benign and malignant small pulmonary nodules (less than 20 mm) from diverse sources. These models have the potential to assist doctors in accurately diagnosing the nature of early-stage lung nodules in clinical practice. Background: The early detection of benign and malignant lung tumors enabled patients to diagnose lesions and implement appropriate health measures earlier, dramatically improving lung cancer patients' quality of living. Machine learning methods performed admirably when recognizing small benign and malignant lung nodules. However, exploration and investigation are required to fully leverage the potential of machine learning in distinguishing between benign and malignant small lung nodules. Objective: The aim of this study was to develop and evaluate the ResNet50-Ensemble Voting model for detecting the benign and malignant nature of small pulmonary nodules (<20 mm) based on CT images. Methods: In this study, 834 CT imaging data from 396 patients with small pulmonary nodules were gathered and randomly assigned to the training and validation sets in an 8:2 ratio. ResNet50 and VGG16 algorithms were utilized to extract CT image features, followed by XGBoost, SVM, and Ensemble Voting techniques for classification, for a total of ten different classes of machine learning combinatorial classifiers. Indicators such as accuracy, sensitivity, and specificity were used to assess the models. The collected features are also shown to investigate the contrasts between them. Results: The algorithm we presented, ResNet50-Ensemble Voting, performed best in the test set, with an accuracy of 0.943 (0.938, 0.948) and sensitivity and specificity of 0.964 and 0.911, respectively. VGG16-Ensemble Voting had an accuracy of 0.887 (0.880, 0.894), with a sensitivity and specificity of 0.952 and 0.784, respectively. Conclusion: Machine learning models that were implemented and integrated ResNet50-Ensemble Voting performed exceptionally well in identifying benign and malignant small pulmonary nodules (<20 mm) from various sites, which might help doctors in accurately diagnosing the nature of early-stage lung nodules in clinical practice. [ABSTRACT FROM AUTHOR]

The concomitant occurrence of 8q duplication and 13q deletion is the first to be detected by noninvasive prenatal testing (NIPT) to date. Through case analysis, we could provide a clinical approach to pregnant women with chromosomal abnormalities revealed by NIPT. The combination of traditional karyotype and copy number variation sequencing (CNV‐seq) could better locate the abnormal chromosomal region and further identify the source of fetal chromosomal abnormalities. Simultaneously, we evaluated the fetal morphology by ultrasound examination. The karyotype of the fetus was 46,XY,der(13)t(8;13)(q22;q32)mat and CNV‐seq results showed that there was an approximately 45.26‐Mb duplication in 8q22.2‐q24.3 (101040001–146 300 000) and an approximately 9.54‐Mb deletion in 13q33.2‐q34 (105560001–115 100 000). Prenatal ultrasound revealed the fetal structural abnormalities presented with hypoplasia of the cerebellar vermis, a flat nose, echogenic bowel and absent gallbladder. Herein, we consider that combination detection of traditional karyotyping, CNV‐seq and ultrasonography provides a valuable method for pregnant women with abnormal NIPT. [ABSTRACT FROM AUTHOR]

Background. Sleep duration is associated with type 2 diabetes (T2D). However, few T2D risk scores include sleep duration. We aimed to develop T2D scores containing sleep duration and to estimate the additive value of sleep duration. Methods. We used data from 43,404 adults without T2D in the Beijing Health Management Cohort study. The participants were surveyed approximately every 2 years from 2007/2008 to 2014/2015. Sleep duration was calculated from the self-reported usual time of going to bed and waking up at baseline. Logistic regression was employed to construct the risk scores. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to estimate the additional value of sleep duration. Results. After a median follow-up of 6.8 years, we recorded 2623 (6.04%) new cases of T2D. Shorter (both 6-8 h/night and <6 h/night) sleep durations were associated with an increased risk of T2D (odds ratio OR = 1.43 , 95% confidence interval CI = 1.30 -1.59; OR = 1.98 , 95 % CI = 1.63 -2.41, respectively) compared with a sleep duration of >8 h/night in the adjusted model. Seven variables, including age, education, waist-hip ratio, body mass index, parental history of diabetes, fasting plasma glucose, and sleep duration, were selected to form the comprehensive score; the C -index was 0.74 (95% CI: 0.71-0.76) for the test set. The IDI and NRI values for sleep duration were 0.017 (95% CI: 0.012-0.022) and 0.619 (95% CI: 0.518-0.695), respectively, suggesting good improvement in the predictive ability of the comprehensive nomogram. The decision curves showed that women and individuals older than 50 had more net benefit. Conclusions. The performance of T2D risk scores developed in the study could be improved by containing the shorter estimated sleep duration, particularly in women and individuals older than 50. [ABSTRACT FROM AUTHOR]

Yucha is a home-made, fermented fish product in South China. The quality of yucha can vary depending on environmental factors. In order to determine the effects of temperature on bacterial biodiversity and quality of fermented yucha products, in the present study, yucha was fermented at 15°C, 20°C, 25°C, and 30°C. Bacterial cells in all yucha samples grew from 3.7 log CFU/g at the onset of the fermentation and reached growth over 7.0 log CFU/g within 1 week. Lactobacillus plantarum was predominated in the 20°C and 25°C fermented yucha products, while Lactobacillus sakei and Lactobacillus brevis were the most abundant in the yucha products fermented at 15°C and 30°C, respectively. Predominant bacterial species are presumed to be potential starters to drive yucha fermentation. Evaluation of yucha qualities demonstrated that lower biogenic amine contents, better texture properties, and more desirable volatile compounds were identified in yucha products fermented at 20°C. Therefore, this temperature is recommended for industrial yucha processing in the future. [ABSTRACT FROM AUTHOR]

Global positioning system (GPS) and inertial navigation system (INS) are commonly combined to overcome disadvantages of each and constitute an integrated system that realizes long-term precision. However, the performance of the integrated system deteriorates on which GPS is unavailable. Especially when low-cost inertial sensors based on the microelectromechanical system (MEMS) are used, performance of the integrated system degrades severely over time. In this study, in order to minimize the adverse impact of high-level stochastic noise from low-cost MEMS sensors, denoising technology based on empirical mode decomposition (EMD) is employed to improve signal quality before navigation solution by which significant improvement of removing noise is achieved. Moreover, a random vector functional link (RVFL) network-based fusion algorithm is presented to estimate and compensate position error during GPS outage such that error accumulation is suppressed quickly when INS is working standalone. Performance of the proposed approach is evaluated by experimental results. It is indicated from comparison that the proposed algorithm takes advantages such as better accuracy and lower complexity and is more robust than the commonly reported methods and is more appropriate for real-time and low-cost application. [ABSTRACT FROM AUTHOR]

Hollow O v -CeO 2 /CdS photocatalyst with atomic-level intimate interface has been synthesized via a defect-induced strategy and exhibits a high hydrogen production rate ∼12.6 mmol·g−1·h−1. [Display omitted] Construction of Z-scheme heterojunction catalysts with high-speed charge transfer channels for efficient photocatalytic hydrogen production from water splitting is still a challenge. In this work, a lattice-defect-induced atom migration strategy is proposed to construct an intimate interface. The oxygen vacancies of cubic CeO 2 obtained from a Cu 2 O template are used to induce lattice oxygen migration and form S O bonds with CdS to form a close contact heterojunction with a hollow cube. The hydrogen production efficiency reaches ∼12.6 mmol·g−1·h−1 and maintains a high value over 25 h. A series of photocatalytic tests combined with density functional theory (DFT) calculations show that the close contact heterostructure not only promotes the separation/transfer of photogenerated electron-hole pairs but also regulates the intrinsic catalytic activity of the surface. A large number of oxygen vacancies and S O bonds at the interface participate in charge transfer, which accelerates the migration of photogenerated carriers. The hollow structure improves the ability to capture visible light. Therefore, the synthesis strategy proposed in this work, as well as the in-depth discussion of the interface chemical structure and charge transfer mechanism, provides new theoretical support for the further development of photolytic hydrogen evolution catalysts. [ABSTRACT FROM AUTHOR]

The rapid advancements in gene therapy have opened up new possibilities for treating genetic disorders, including Duchenne muscular dystrophy, thalassemia, cystic fibrosis, hemophilia, and familial hypercholesterolemia. The utilization of the clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) system has revolutionized the field of gene therapy by enabling precise targeting of genes. In recent years, CRISPR/Cas9 has demonstrated remarkable efficacy in treating cancer and genetic diseases. However, the susceptibility of nucleic acid drugs to degradation by nucleic acid endonucleases necessitates the development of functional vectors capable of protecting the nucleic acids from enzymatic degradation while ensuring safety and effectiveness. This review explores the biomedical potential of non-viral vector-based CRISPR/Cas9 systems for treating genetic diseases. Furthermore, it provides a comprehensive overview of recent advances in viral and non-viral vector-based gene therapy for genetic disorders, including preclinical and clinical study insights. Additionally, the review analyzes the current limitations of these delivery systems and proposes avenues for developing novel nano-delivery platforms. [ABSTRACT FROM AUTHOR]

Supramolecular self‐assembly stands for the spontaneous aggregation of small organic compounds or polymers into ordered structures at any scale. When being induced by inherent molecular chiral centers or ambient asymmetric factors, asymmetric spatial arrangement between building units shall occur, which is defined as supramolecular chirality. Except for molecular design, utilizing external stimulus factors to tune supramolecular chirality is a promising approach. In this Concept article, we particularly discuss the important role of solvents in manipulating the chirality of self‐assembled systems. The impact of solvents on the chirality is generally based on three properties of solvents, i.e. chirality, polarity, and active coassembly with building blocks. Molecular self‐assembly in chiral solvents could undergo the chirality transfer, exhibiting a chiral induction effect. Solvent polarity often determines intermolecular orientation. As a consequence, those building blocks with both polar and apolar segments might change their chirality depending on the solvent polarity. We elaborate the active participation of solvent molecules into ordered structures together with building blocks, where solvents and building blocks exhibit a coassembly manner. By specific treatments such as heating and cooling, solvents could be released or re‐entrapped, allowing a smart control over supramolecular chirality. The solvent effect in manipulating two‐dimensional chiral self‐assemblies is then discussed. The perspective and future development in this research field are presented at last. [ABSTRACT FROM AUTHOR]

This paper presents a comprehensive study on the numerical and parametric study of geocell-reinforced cohesive soil beds, focusing on different infill materials. The numerical calculations were validated against model test results using FLAC3D software. Subsequently, the verified model was expanded to the geocell-reinforced cohesive soil beds. Six cases were simulated to investigate the reinforced performance, including pressure-settlement responses, bearing capacity improvement factor, settlement reduction percentage, and surface deformation. The numerical findings emphasize that the significance of superior geocell reinforcement should not overshadow the consideration of soil infill's mechanical properties. In the case of cohesive soil as the infill material, the poor improvement in geocell-reinforced performance may be attributed to its low modulus and cohesion. Parametric studies suggest that geocells significantly impact reinforced performance when the infill material consists of foundation soil with a higher modulus and lower cohesion. Further, according to this numerical study, cohesionless soil with a modulus of 20 MPa and friction of 40° is the optimum infill soil in pockets to reinforce cohesive soil beds. [ABSTRACT FROM AUTHOR]

Excessive accumulation of chloride (Cl−) in the aboveground tissues under saline conditions is harmful to crops. Increasing the exclusion of Cl− from shoots promotes salt tolerance in various crops. However, the underlying molecular mechanisms remain largely unknown. In this study, we demonstrated that a type A response regulator (ZmRR1) modulates Cl− exclusion from shoots and underlies natural variation of salt tolerance in maize. ZmRR1 negatively regulates cytokinin signaling and salt tolerance, likely by interacting with and inhibiting His phosphotransfer (HP) proteins that are key mediators of cytokinin signaling. A naturally occurring non-synonymous SNP variant enhances the interaction between ZmRR1 and ZmHP2, conferring maize plants with a salt-hypersensitive phenotype. We found that ZmRR1 undergoes degradation under saline conditions, leading to the release of ZmHP2 from ZmRR1 inhibition, and subsequently ZmHP2-mediated signaling improves salt tolerance primarily by promoting Cl− exclusion from shoots. Furthermore, we showed that ZmMATE29 is transcriptionally upregulated by ZmHP2-mediated signaling under highly saline conditions and encodes a tonoplast-located Cl− transporter that promotes Cl− exclusion from shoots by compartmentalizing Cl− into the vacuoles of root cortex cells. Collectively, our study provides an important mechanistic understanding of the cytokinin signaling-mediated promotion of Cl− exclusion from shoots and salt tolerance and suggests that genetic modification to promote Cl− exclusion from shoots is a promising route for developing salt-tolerant maize. This study shows that cytokinin promotes high-Cl– tolerance in maize. Salt stress induces the degradation of ZmRR1, a negative regulator of cytokinin signaling, to relieve its inhibition of ZmHP2, which in turn upregulates the expression of ZmMATE29. ZmMATE29, which is capable of Cl− transport, promotes shoot Cl− exclusion and salt tolerance by compartmentalizing Cl− into the vacuoles of the root cortex cells. [ABSTRACT FROM AUTHOR]

Transplanting human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) tissue sheets effectively treat ischemic cardiomyopathy. Cardiac functional recovery relies on graft survival in which angiogenesis played an important part. ONO-1301 is a synthetic prostacyclin analog with proangiogenic effects. We hypothesized that transplantation of hiPSC-CM tissue sheets with slow-release ONO-1301 scaffold could promote hostgraft angiogenesis, enhance tissue survival and therapeutic effect. We developed hiPSC-CM tissue sheets with ONO-1301 slow-release scaffold and evaluated their morphology, gene expression, and effects on angiogenesis. Three tissue sheet layers were transplanted into a rat myocardial infarction (MI) model. Left ventricular ejection fraction, gene expression in the MI border zone, and angiogenesis effects were investigated 4 weeks after transplantation. In vitro assessment confirmed the slow-release of ONO-1301, and its pro-angiogenesis effects. In addition, in vivo data demonstrated that ONO-1301 administration positively correlated with graft survival. Cardiac tissue as thick as ∼900 μm was retained in the ONO (+) treated group. Additionally, left ventricular ejection fraction of the ONO (+) group was significantly enhanced, compared to ONO (−) group. The ONO (+) group also showed significantly improved interstitial fibrosis, higher capillary density, increased number of mature blood vessels, along with an enhanced supply of oxygen, and nutrients. Slow-release ONO-1301 scaffold provided an efficient delivery method for thick hiPSC-CM tissue. ONO-1301 promotes angiogenesis between the host and graft and improves nutritional and oxygen supply, thereby enhancing the survival of transplanted cells, effectively improving ejection fraction, and therapeutic effects. [ABSTRACT FROM AUTHOR]

Dysregulated microRNAs (miRNAs) have been reported to involve in the pathophysiological process of traumatic brain injury (TBI), and modulate autophagy-related genes (ATGs) expression. Our previous studies showed that neuronal autophagy was activated in the injury hippocampus post- TBI and associated with neurological and cognitive impairments. The present study was designed to investigate the possible role of miR-23b in TBI-induced cognitive impairments. We found the overexpression of miR-23b conferred a better neuronprotective effects after TBI by decreasing lesion volume, alleviating brain edema, inhibiting neuron apoptosis and attenuating long-term neurological deficits, and most interestingly, improving cognitive impairments. To further explore the molecular underlying this neuronprotection, we evaluated autophagic activity and ATG12 expression in the injury hippocampus CA1 region. The results identified that miR-23b directly targeted to the 3′UTR region of ATG12 mRNA to suppress the activation of neuronal autophagy by a dual-luciferase reporter system. Notably, overexpression of ATG12 abrogated the neuronprotective effects of miR-23b on TBI-induced neurological and cognitive impairments. Taken together, these date revealed inhibition of ATG12-mediated autophagic activity by miR-23b overexpression might be involve in cognitive improvement after TBI, indicating that miR-23b might be a potential therapeutic target for TBI. [ABSTRACT FROM AUTHOR]

Premise: The ~140 species of Lonicera are characterized by variously fused leaves, bracteoles, and ovaries, making it a model system for studying the evolution and development of organ fusion. However, previous phylogenetic analyses, based mainly on chloroplast DNA markers, have yielded uncertain and conflicting results. A well‐supported phylogeny of Lonicera will allow us to trace the evolutionary history of organ fusion. Methods: We inferred the phylogeny of Lonicera using restriction site–associated DNA sequencing (RADSeq), sampling all major clades and 18 of the 23 subsections. This provided the basis for inferring the evolution of five fusion‐related traits. Results: RADSeq data yielded a well‐resolved and well‐supported phylogeny. The two traditionally recognized subgenera (Periclymenum and Chamaecerasus), three of the four sections (Isoxylosteum, Coeloxylosteum, and Nintooa), and half of the subsections sampled were recovered as monophyletic. However, the large and heterogeneous section Isika was strongly supported as paraphyletic. Nintooa, a clade of ~22 mostly vine‐forming species, including L. japonica, was recovered in a novel position, raising the possibility of cytonuclear discordance. We document the parallel evolution of fused leaves, bracteoles, and ovaries, with rare reversals. Most strikingly, complete cupules, in which four fused bracteoles completely enclose two unfused ovaries, arose at least three times. Surprisingly, these appear to have evolved directly from ancestors with free bracteoles instead of partial cupules. Conclusions: We provide the most comprehensive and well‐supported phylogeny of Lonicera to date. Our inference of multiple evolutionary shifts in organ fusion provides a solid foundation for in depth developmental and functional analyses. [ABSTRACT FROM AUTHOR]

Summary: Drought is a major environmental stress that threatens crop production. Therefore, identification of genes involved in drought stress response is of vital importance to decipher the molecular mechanism of stress signal transduction and breed drought tolerance crops, especially for maize.Clade A PP2C phosphatases are core abscisic acid (ABA) signaling components, regulating ABA signal transduction and drought response. However, the roles of other clade PP2Cs in drought resistance remain largely unknown. Here, we discovered a clade F PP2C, ZmPP84, that negatively regulates drought tolerance by screening a transgenic overexpression maize library.Quantitative RT‐PCR indicates that the transcription of ZmPP84 is suppressed by drought stress. We identified that ZmMEK1, a member of the MAPKK family, interacts with ZmPP84 by immunoprecipitation and mass spectrometry analysis. Additionally, we found that ZmPP84 can dephosphorylate ZmMEK1 and repress its kinase activity on the downstream substrate kinase ZmSIMK1, while ZmSIMK1 is able to phosphorylate S‐type anion channel ZmSLAC1 at S146 and T520 in vitro. Mutations of S146 and T520 to phosphomimetic aspartate could activate ZmSLAC1 currents in Xenopus oocytes.Taken together, our study suggests that ZmPP84 is a negative regulator of drought stress response that inhibits stomatal closure through dephosphorylating ZmMEK1, thereby repressing ZmMEK1–ZmSIMK1 signaling pathway. [ABSTRACT FROM AUTHOR]

Background/Aims: Our previous microarray results identified numerous microRNAs (miRNAs), including miR-29b, that were differentially expressed in the serum of intracranial aneurysm (IA) patients. The current study aimed to investigate whether miR-29b downregulation in IA could promote the phenotypic modulation of vascular smooth muscle cells (VSMCs) involved in the pathogenesis of aneurysm by activating ATG14-mediated autophagy. Methods: First, the levels of miR-29b and autophagy related genes (ATGs) between IA patients and normal subjects were compared. Next, we modified the level of miR-29b via lentivirus particles in the VSMCs and examined the effects of miR-29b on proliferation, migration, and phenotypic modulation of VSMCs from a contractile phenotype to a synthetic phenotype, as well as the levels of autophagy. Finally, the binding of miR-29b to the 3'UTR of ATG14 mRNA and its effects on ATG14 expression were analysed by a luciferase reporter assay and Western blot, respectively. Results: The level of miR-29b was decreased, and autophagy markers were increased in the IA patients compared to that of the normal subjects. Knockdown of miR-29b significantly promoted VSMCs proliferation and migration and, more importantly, induced the phenotypic modulation associated with autophagy activation, whereas miR-29b overexpression showed the opposite effects. The luciferase reporter assay demonstrated that ATG14 was a functional target gene of miR-29b. Notably, knockdown of ATG14 by siRNA apparently abrogated miR- 29b inhibition-mediated phenotypic modulation. Conclusion: Downregulation of miR-29b induced VSMCs phenotypic modulation by directly activating ATG14-mediated autophagy, which is associated with the formation, growth and rupture of IAs. [ABSTRACT FROM AUTHOR]

[Objective] To establish drought resistance evaluation index system of desert shrubs, and provide scientific support for selecting quality tree species. [Method] Taking 2-year-old seedlings of 12 desert shrubs in Ulan Buh Desert ecosystem as the test materials, 7 water physiological indexes were tested, principal component analysis and cluster analysis were applied to explore drought resistance of the shrubs. [Results] (a) Water potential of Ephedra, distachya Linn., Nitraia tangutorum Bobr., Caragana korshinskii Kom. was lower than that of the other 9 species; bound water content (Va) and bound water/free water ratio (Va\Vs) of ZygophyUum xanthoxylon Maxim, was 64.20% and 3.3, higher than the others'; transpiration rate of Atraphaxis bracteata A. Los., Nitraia tangutorum Bobr. and Tamarix elongata Ldb. was significantly lower than the others'; constant weight time of Haloxylon ammodendron (C. A. Mey.) Bunge and Ephedra distachya Linn, was the longest (144 h); residual moisture content of Ammopiptanthus mongolicus Maxim, was the highest (44.80%). (b) Water potential, bound water/free water (Va/Vs), residual moisture content, bound water, constant weight time, and transpiration rate had great impact on drought resistance of plant, and the accumulative variance contribution rate achieved 87.59%. [Conclusion] According to the drought resistance, the 12 species were classified into 3 categories, namely shrubs with strong drought resistance (Ephedra distachya linn.), shrubs with moderate drought resistance (Haloxylon ammodendron (C. A. Mey.) Bunge, Nitraia tangutorum Bobr., and ZygophyUum xanthoxylon Maxim.); shrubs with poor drought resistance (Hedysarunn scoparium Fisch, Hedysarum mongolicum Turcz., Tamarix elongata Ldb., Caragana korshinskii Kom., Ammopiptanthus mongolicus Maxim., Atraphaxis bracteata A. Los., Calligonum mongolicum Mattel, and Caragana microphyila Lam.). [ABSTRACT FROM AUTHOR]

Flexible polymer-based magnetoelectric (ME) materials have broad application prospects and are considered as a new research field. In this article, FeCoSiB thin films were deposited on poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) substrate by DC magnetron sputtering. The structure of PVDF-TrFE/FeCoSiB heterostructure thin films was similar to 2-2. Under a bias magnetic field of 70 Oe, the composites have a dramatically increased ME voltage coefficient as high as 111 V/cm⋅Oe at a frequency of about 85 kHz. The piezoelectric coefficient of PVDF-TrFE thin films is 34.87 pC/N. The surface morphology of PVDF-TrFE thin films were studied by FESEM, and the results of XRD and FTIR showed that the β-phase of PVDF-TrFE thin films was dominant. Meanwhile, the effects of different heating conditions on the crystallization and piezoelectric properties of PVDF-TrFE films were also studied. The flexible ME heterojunction composite has a significant ME voltage coefficient and excellent piezoelectric properties at room temperature, which allows it to be a candidate material for developing flexible magnetoelectric devices. [ABSTRACT FROM AUTHOR]

Background: Health interventions can delay or prevent the occurrence and development of diabetes. Dynamic nomogram and risk score (RS) models were developed to predict the probability of developing type 2 diabetes mellitus (T2DM) and identify high-risk groups. Methods: Participants (n = 44,852) from the Beijing Physical Examination Center were followed up for 11 years (2006–2017); the mean follow-up time was 4.06 ± 2.09 years. Multivariable Cox regression was conducted in the training cohort to identify risk factors associated with T2DM and develop dynamic nomogram and RS models using weighted estimators corresponding to each covariate derived from the fitted Cox regression coefficients and variance estimates, and then undergone internal validation and sensitivity analysis. The concordance index (C-index) was used to assess the accuracy and reliability of the model. Results: Of the 44,852 individuals at baseline, 2,912 were diagnosed with T2DM during the follow-up period, and the incidence density rate per 1,000 person-years was 16.00. Multivariate analysis indicated that male sex (P < 0.001), older age (P < 0.001), high body mass index (BMI, P < 0.05), high fasting plasma glucose (FPG, P < 0.001), hypertension (P = 0.015), dyslipidaemia (P < 0.001), and low serum creatinine (sCr, P < 0.05) at presentation were risk factors for T2DM. The dynamic nomogram achieved a high C-index of 0.909 in the training set and 0.905 in the validation set. A tenfold cross-validation estimated the area under the curve of the nomogram at 0.909 (95% confidence interval 0.897–0.920). Moreover, the dynamic nomogram and RS model exhibited acceptable discrimination and clinical usefulness in subgroup and sensitivity analyses. Conclusions: The T2DM dynamic nomogram and RS models offer clinicians and others who conduct physical examinations, respectively, simple-to-use tools to assess the risk of developing T2DM in the urban Chinese current or retired employees. [ABSTRACT FROM AUTHOR]

Background: Arterial stiffness, glycemic control and blood pressure are risk factors of macrovascular complications in type 2 diabetes. This study aimed to investigate the combined association of arterial stiffness, glycemic control and hypertension status with the occurrence of diabetic macrovascular complication. Methods: A total of 1870 patients of diabetes were enrolled from Beijing Health Management Cohort between 2008 and 2018 as baseline, and then followed for macrovascular complication onset. We proposed a composite risk score (0–4) by arterial stiffness severity, pool glycemic control and hypertension status. Cox model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results: The mean age (SD) of this population was 59.90 (12.29) years. During a median follow-up of 4.0 years, 359 (19.2%) patients developed macrovascular complication. Compared to the normal arterial stiffness and good glycemic control group, patients with severe arterial stiffness and pool glycemic control had the highest risk of macrovascular complications (HR: 2.73; 95% CI: 1.42–5.25). Similarly, those of severe arterial stiffness and hypertension had the highest risk (HR: 2.69; 95% CI: 1.61–4.50). Patients of the composite score > 2 had a significantly increased risk of macrovascular complication. Conclusion: This study suggested the clinical importance of combined evaluation of arterial stiffness, glycemic control and hypertension status for the risk stratification and management of macrovascular complication of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Background: Superior cerebellar artery (SCA) syndrome shows ipsilateral cerebellar ataxia and Horner''s syndrome, contralateral superficial sensory disturbance, as well as nystagmus toward the impaired side, vertigo, and nausea. Occasionally, unilateral lesions may produce bilateral hypogeusia and contralateral hypoacusia. Objective: To report 2 patients with unilateral lower midbrain ischemic lesions of the inferior colliculus level caused by transarterial embolization for tentorial dural arteriovenous fistulas (TDAVFs). Methods: Hospital records for 21 patients with TDAVFs mainly treated by endovascular techniques between 2005 and 2008 were reviewed. Two patients with MRI evidence of unilateral SCA territory infarction were investigated. Results: Of 21 patients, 2 treated transarterially with Onyx-18 (a nonahesive liquid embolic agent) developed infarctions in the territory of SCA. One patient had lateral SCA infarction characterized by ipsilateral gait ataxia, contralateral hemihypoesthesia, with additional ipsilateral ocular motor palsy and bilateral gustatory loss. And the other patient had medial SCA infarction characterized by ipsilateral ataxia contralateral hemihypoesthesia with additional contralateral hypoacusia. Conclusion: SCA infarction can be caused by transarterial injection of Onyx-18 via SCA or the posterior cerebral artery (PCA) for TDAVFs and additionally presented with gustatory loss and deafness, which is generally not a feature of the SCA syndrome. [Copyright &y& Elsevier]

The calcineurin B-like-interacting protein kinase (CIPK) protein family plays a key role in the plant calcium ion-mediated signal transduction pathway, which regulates a plant's response to abiotic stress. Nitraria sibirica pall. (N. sibirica) is a halophyte with a strong tolerance for high salt environments, yet how it is able to deal with salt stress on a molecular level is still unknown. Due to their function as described in other plant species, CIPK genes are prime candidates for a role in salt stress signaling in N. sibirica. In this study, we identified and analyzed the phylogenetic makeup and gene expression of the N. sibirica CIPK gene family. A total of 14 CIPKs were identified from the N. sibirica genome and were clustered into seven groups based on their phylogeny. The promoters of NsCIPK genes contained multiple elements involved in hormonal and stress response. Synteny analysis identified a total of three pairs of synteny relationships between NsCIPK genes. Each gene showed its own specific expression pattern across different tissues, with the overall expression of CIPK6 being the lowest, and that of CIPK20 being the highest. Almost all CIPK genes tended to respond to salt, drought, and cold stress, but with different sensitivity levels. In this study, we have provided a general description of the NsCIPK gene family and its expression, which will be of great significance for further understanding of the NsCIPK gene family function. [ABSTRACT FROM AUTHOR]

Objective. The aims of this study were to investigate the impact of TAK-242 on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) signal transduction pathway in rats with hepatic fibrosis (HF) using the liver gut axis and to investigate the molecular mechanism of its intervention on HF. Methods. SPF grade SD male rats were randomly allocated to the control, model, and TAK-242 groups. For 8 weeks, the model and TAK-242 groups received 3 mL·kg-1 (the initial dose 5 mL·kg-1) intraperitoneal injections of 40% CCL4 olive oil solution. TAK-242 (5 mg·kg-1) was administered once a day for 5 days after modeling. The pathological alterations of liver and small intestine tissues in each group were observed using H&E and Masson staining. ELISA was used to measure serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBIL), total bilirubin (TBIL), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). RT-qPCR was utilized to identify the mRNA expression level of IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB in rat liver and small intestine tissues. The protein level of IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB protein in rat liver and small intestine tissues was determined utilizing Western blot and IHC. Results. TAK-242 significantly reduced AST, ALT, TBIL, and DBIL expression in HF rats' serum (P < 0.01) and alleviated liver tissue injury. Hematoxylin-eosin (H&E) and Masson staining revealed inflammatory cell infiltration and fibrous proliferation in the liver and small intestine tissue in the model group and partial cell swelling in the TAK-242 group, which indicated a considerable improvement compared to the model group. RT-qPCR, Western blot, and IHC data indicated that TAK-242 reduced the IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB expression in the liver and small intestine tissues of HF rats. Conclusion. TAK-242 might downregulate the TLR4/MyD88/NF-κB signal pathway through the liver-gut axis, suppress the inflammatory response, and eventually alleviate HF in rats. [ABSTRACT FROM AUTHOR]

A novel two-phase method was employed to directly deposit PbS quantum dots (QDs) on nanocrystalline SnO thin films. In the two-phase method, the nanocrystalline SnO thin film with adsorption of Pb ions was placed in an aqueous solution, and S ions were dissolved in an oil solution. As two solutions were contacted, S ions prefer to transfer to the aqueous solution and diffuse to the thin film surface with the adsorbed Pb ions to homogeneously form monodispersed PbS QDs on the nanocrystalline thin film. The homogeneous monodispersed QDs-sensitized thin film was used as a photoelectrode to fabricate QDs-sensitized solar cell. The loaded amount of PbS QDs and the thickness of ZnS passivation layer were optimized to obtain the highest light-to-electric conversion efficiency of 1.01 % under the simulated AM 1.5 illumination, which is increased by 61 % compared with that of the PbS QDs-sensitized solar cell employing the successive ionic layer adsorption and reaction (SILAR). The solar cell with homogeneous sensitization of QDs generates a photocurrent density of 11.09 mA·cm, which is 2.4 times higher than that of the unhomogeneous one prepared by SILAR. The conversion efficiency enhancement mechanism due to the two-phase method was discussed in detail through the measurements of intensity-modulated photovoltage spectrum and electrochemical impedance spectroscopy. [ABSTRACT FROM AUTHOR]

Modulating the electronic configuration by coupling multi-scale active sites for electrocatalytic conversion of CO 2 to CO is extremely challenging in terms of structural analysis and mechanism elucidation. Herein, a catalyst NiAD/AgNPs@CN with both atomic-level dispersed Ni and Ag nanoparticles on N-doped carbon substrate has been designed to reveal the true active sites and catalytic mechanism in complex materials. NiAD/AgNPs@CN exhibits CO Faraday efficiency (FE CO) of 99.97% at −0.88 V (vs. RHE) in H-type cell and 91.77% FE CO with a high current density of 79.70 mA/cm2 in flow cell. DFT calculations show that the tiny change in the energy level of spin electrons at atomic sites has a significant impact on the CO 2 activation. The regulation of atomic Ni on Ag sites is the main reason for improving CO 2 RR performance. This work gives a new understanding on the catalytic mechanism of composite materials structured by atomic-level dispersed metal and nanoparticles. [Display omitted] • Atomic dispersed Ni surrounding with Ag nanoparticles was designed for CO 2 RR. • The synergistic effect between Atomic Ni sites and Ag nanoparticles was deeply explored. • Experiments combined with DFT study revealed the CO 2 RR mechanism. • The tiny change of spin electrons state has a significant impact on the activation of CO 2. [ABSTRACT FROM AUTHOR]

• ●A magnetic-responsive Fe 3 O 4 @SiO 2 -MPS-PILs were synthesized. • ●The material possessed abundant imidazole units, benzene rings and ionic bonds. • ●The adsorbent could simultaneously remove iodine and iodide ions from solutions. • ●The material maintained over 90% of the uptake capacity after five cycles. Nuclear waste management and nuclear energy generation require the proper disposal of 129I and 131I, which are radioactive isotopes of iodine. For recognition of different types' iodine, a magnetic poly (ionic liquid)s (Fe 3 O 4 @SiO 2 -MPS-PILs) was formed by the selected imidazole ionic liquid monomer and core–shell Fe 3 O 4 @SiO 2 -MPS via free radical polymerization. The resulting adsorbent containing plenty of imidazole N-heterocycle units, benzene rings, and ionic bonds in the backbones was suitable for simultaneously adsorbing iodine molecules and iodide ions. The adsorption mechanisms for iodine in cyclohexane and iodide ions from aqueous solution were based on charge transfer and ion exchange mechanisms, respectively. The adsorption equilibrium for iodine in cyclohexane was attained at 12 h, and the kinetics of iodine adsorption closely followed the pseudo-second-order model. Iodine adsorption on Fe 3 O 4 @SiO 2 -MPS-PILs was best described by Langmuir model with a maximum iodine adsorption capacity of approximately 714.29 mg g−1. Iodide ions adsorption was best explained with Freundlich model and a maximum adsorption capacity of 335.80 mg g−1 was achieved in an iodide solution with a 500 mg L–1 concentration. Notably, Fe 3 O 4 @SiO 2 -MPS-PILs retained over 90 % of its original adsorption performance after the 5th cycle. This work proves that the adsorbent Fe 3 O 4 @SiO 2 -MPS-PILs was efficient and recyclable, and has good application prospects in the practical treatment of iodine and iodide. [ABSTRACT FROM AUTHOR]

Background: Human-induced pluripotent stem cells (hiPSCs) are considered an ideal resource for regenerative medicine because of their ease of access and infinite expansion ability. To satisfy the sizable requirement for clinical applications of hiPSCs, large-scale, expansion-oriented, xeno-free, and cost-effective media are critical. Although several xeno-free media for hiPSCs have been generated over the past decades, few of them are suitable for scalable expansion of cultured hiPSCs because of their modest potential for proliferation and high cost. Methods: In this study, we developed a xeno-free ON2/AscleStem PSC medium (ON2) and cultured 253G1 hiPSCs on different matrices, including iMatrix-511 and gelatin nanofiber (GNF) in ON2. Over 20 passages, we evaluated cell proliferation by doubling times; pluripotency by flow cytometry, immunofluorescence staining and qRT-PCR; and differentiation ability by three germ layer differentiation in vitro and teratoma formation in severe combined immunodeficiency mice, followed by histological analysis. In addition, we compared the maintenance effect of ON2 on hiPSCs with StemFit® AK02 (AK02N) and Essential 8™ (E8). Besides 253G1 hiPSCs, we cultivated different hiPSC lines, including Ff-l01 hiPSCs, ATCC® ACS-1020™ hiPSCs, and Down's syndrome patient-specific ATCC® ACS-1003™ hiPSCs in ON2. Results: We found that 253G1 hiPSCs in ON2 demonstrated normal morphology and karyotype and high self-renewal and differentiation abilities on the tested matrices for over 20 passages. Moreover, 253G1 hiPSCs kept on GNF showed higher growth and stemness, as verified by the shorter doubling time and higher expression levels of pluripotent markers. Compared to AK02N and E8 media, 253G1 hiPSCs grown in ON2 showed higher pluripotency, as demonstrated by the increased expression level of pluripotent factors. In addition, all hiPSC lines cultivated in ON2 were able to grow for at least 10 passages with compact clonal morphology and were positive for all detected pluripotent markers. Conclusions: Our xeno-free ON2 was compatible with various matrices and ideal for long-term expansion and maintenance of not only healthy-derived hiPSCs but also patient-specific hiPSCs. This highly efficient medium enabled the rapid expansion of hiPSCs in a reliable and cost-effective manner and could act as a promising tool for disease modeling and large-scale production for regenerative medicine in the future. [ABSTRACT FROM AUTHOR]

A TiO 2 compact layer was coated on fluorine-doped tin oxide (FTO) glass substrate prior to deposition of SnO 2 nanocrystalline thin film to suppress backflow of electrons from FTO to the SnO 2 nanocrystalline thin film. The resultant thin film was used as a photoelectrode to fabricate dye-sensitized solar cell. For comparison, a SnO 2 compact layer was also prepared to discuss the effect of the TiO 2 compact layer on the electron backflow process. Compared with the dye-sensitized SnO 2 nanocrystalline thin film solar cell without the compact layer, light-to-electric conversion efficiency for the solar cell with the TiO 2 compact layer was improved by 82.1% and it was even improved by 41.7% compared with the cell with the SnO 2 compact layer. Electrochemical impedance spectroscopy and open-circuit voltage decay of dye-sensitized solar cells were measured to demonstrate the improvement mechanism due to the TiO 2 compact layer. Both recombination resistance at the photoelectrode/electrolyte interface and lifetime of electrons on the SnO 2 nanocrystalline thin film were increased due to introduction of the TiO 2 compact layer. Because the conduction band of TiO 2 is higher than that of SnO 2 , the TiO 2 compact layer acts as not only a physical barrier to separate FTO substrate from electrolyte, thus suppressing recombination of electrons on FTO with the electrolyte, but also a potential barrier to effectively block the backflow of electrons from FTO substrate to the SnO 2 thin film. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease characterized by a disorder of the dopaminergic system in the midbrain, causing classical PD motor symptoms. The therapeutic effect of cannabidiol (CBD) on PD has been a research frontier in recent years. However, the pathogenesis of PD and the therapeutic mechanism of cannabinoid remain unclear. To further study the causes of PD and the effect of CBD on PD, we exposed the PD transgenic mouse model to CBD and then estimated the motorial and postural coordination through a modified swim test. Afterwards, the mechanism was investigated via the histopathology of substantia nigra and the gut-brain metabolic analysis in the approach of UHPLC-TOF-MS. The results showed that CBD significantly improved motor deficits of PD model and protected the substantia nigra area. The metabolic function of fatty acid biosynthesis, arginine biosynthesis/metabolism, butanoate (ketone body) metabolism, β-alanine metabolism, and pantothenate/CoA biosynthesis was highlighted in the pathological and therapeutic process along the gut-brain axis. In conclusion, CBD could attenuate PD via the neuroprotective effect on the midbrain. The attenuation of the central nervous system in turn improved motor performance of PD, which might be partially induced by the metabolic interaction between the gut-brain. In view of gut-brain metabolomics, the mechanism of PD pathogenesis and the effect of CBD on PD are highly related to the biosynthesis and metabolism of energy and essential substance. [ABSTRACT FROM AUTHOR]

Newly identified PD-1hiCXCR5–CD4+ T-cells, termed as peripheral helper T-cells (Tph), have been found elevated and playing a pathogenic role in some autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatic arthritis (RA). However, the potential role of Tph-cells in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains unclear. Here, we explored the potential clinical significance of circulating Tph-cells in the pathogenesis of AAV. Comparing 32 active AAV patients and 18 age- and sex-matched healthy controls (HCs), we found that the frequency of circulating Tph-cells was significantly expanded in active AAV patients. Besides, programmed death 1 (PD-1) expression on the surface of Tph-cells was significantly up-regulated in active AAV patients. Importantly, the frequency of circulating Tph-cells was greatly decreased in AAV patients after receiving treatment. Tph-cells frequency was positively correlated with the Birmingham Vasculitis Activity Score (BVAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil lymphocyte ratio (NLR), and cellular crescent in active AAV patients, but negatively correlated with fibrosus crescent. Tph-cells frequency was also positively correlated with naïve B-cells, serum concentration of MPO-ANCAs, serum tumor necrosis factor-α (TNF-α), IL-4, IL-21, and IL-12. However, serum IL-10 exhibited a negative correlation with circulating Tph-cells in active AAV patients. These results demonstrate that circulating Tph-cells are greatly expanded in active AAV patients and are positively associated with serum MPO-ANCAs and disease activity, thus contributing to the pathogenesis of AAV. The role of newly identified peripheral helper T cells (Tph) in ANCA-associated vasculitis (AAV) remains largely unknown, although they have been found elevated and playing pathogenic role in some autoimmune disease including SLE and RA. In this study, Liu et al found that Tph cells were greatly expanded in active AAV patients and decreased after treatment with methylprednisolone and cyclophosphamide, and they were positively correlated with vasculitis activity index, serum concentration of MPO-ANCA, IL-4 and IL-21. These results indicate that Tph cells may play a pathogenic role in AAV through promoting plasma cell activation possibly by secreting IL-4 and IL-21. [ABSTRACT FROM AUTHOR]

Forests and grasslands play a significant role in global nitrous oxide (N2O) emission, while a sophisticated model is missing to interpret the microbial processes involved in N2O production and consumption in these ecosystems. A new N2O emission model, MicN model, was developed for natural forest and grassland ecosystems by integrating with Integrated BIosphere Simulator (IBIS). This new model includes four major N2O correlated processes: autotrophic nitrification, heterotrophic nitrification, nitrifier denitrification and denitrifier denitrification. Thirty‐nine observation sites, including various forest and grassland ecosystem types, were selected to calibrate and validate IBIS‐MicN model. The IBIS‐MicN model explained 89% and 85% of observed daily variability in N2O emission for all calibration and validation sites, respectively. In addition, the model successfully predicted the concentrations of two important intermediates (i.e., ammonium and nitrate) for N2O production at nine validation sites. Compared with Forest‐DNDC model, IBIS‐MicN model performed better in simulating N2O emission, soil NH4+ and NO3−concentrations. At site scale, the simulated N2O emissions by IBIS‐MicN model positively correlated with annual mean soil temperature and annual precipitation, but negatively correlated with soil pH. This study provides an alternative model to estimate global N2O emission from natural forest and grassland ecosystems and to investigate corresponding environmental regulations. Plain Language Summary: A new process‐based model (IBIS‐MicN model) was developed to estimate N2O emission from forest and grassland ecosystems. Four microbial processes, autotrophic nitrification, heterotrophic nitrification, nitrifier denitrification and denitrifier denitrification, were considered in the new model. In addition, IBIS‐MicN model depicted the related microbial dynamics and simulated intermediate products (i.e., ammonium and nitrate) of N2O production. The model reproduced the magnitude and seasonality of ammonium, nitrate and N2O emission at 39 global observation sites very well, which implying the robust model structure and performance for reproducing soil N2O emission. We then analyzed the response of N2O emissions to meteorological and environmental variables, including air temperature, precipitation and soil pH. Key Points: The new model simulated four major N2O related processes and the microbial dynamics related to N2O production and consumptionThe IBIS‐MicN model explained 89% and 85% of observed daily variability in N2O emission at calibration and validation sitesThe new model performed better than Forest‐DNDC model for reproducing the observed daily N2O emission, and concentration of NH4+ and NO3− at site‐scale [ABSTRACT FROM AUTHOR]

• The pathogenesis of ANCA-associated vasculitis (AAV) has not been fully elucidated yet. • Neutrophils and glomerular endothelial cells have important effector and regulatory functions in renal iflammatory. • The increase of both CXCL16 level and CXCR6 were observed in AAV patients. • The increase of CXCL16 released from glomerular endothelial cells treated with AAV patient's sreum. • CXCL16/CXCR6 might play a role in the pathogenesis of AAV. Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a group of potentially life-threatening autoimmune diseases. The kidney and lung are the most common and most severely affected organs. Previous studies have shown that the chemokine ligand CXCL16 and its receptor CXCR6 play an important role in kidney disease. However, whether CXCL16/CXCR6 is involved in the pathogenesis of AAV remains elusive. In this study, the levels of CXCL16 and its specific receptor CXCR6 were investigated. According to kidney outcome, patients were divided into two groups, specifically one with high CXCL16 levels and one with low CXCL16 levels, by cut-off values using receiver operating characteristic (ROC) curves. The clinical parameters and histological features were further compared between the two groups. The ability of CXCL16 to induce neutrophil chemotaxis was analysed using a Transwell migration assay in a coculture system of conditional immortalized human glomerular endothelial cells (ciGEnCs) and neutrophils. We observed that the levels of CXCL16 were significantly increased in the circulation, along with the expression in renal tissue of AAV patients compared to healthy controls (HCs). CXCR6 expression on neutrophils was significantly higher in patients with AAV than in HCs. There were positive correlations between the levels of CXCL16 and serum creatinine, IL-6, CRP, and TNF-α and negative correlations with eGFR. The serum levels of CXCL16 could act as a predictive biomarker of renal outcome in AAV. CXCL16 secretion was upregulated in ciGEnCs treated with AAV serum. CXCL16 released from ciGEnCs contributed to neutrophil migration. Furthermore, neutrophil migration was attenuated by silencing CXCL16 expression via transfection with short hairpin RNA (shRNA) sequences and lentivirus. Taken together, these data suggest that the inhibition of the CXCL16/CXCR6 axis may provide new therapeutic strategies targeting AAV. [ABSTRACT FROM AUTHOR]