Monolayer NbSe2 Favors Ultralow Friction and Super Wear Resistance.

The urgent demand for atomically thin, superlubricating, and super wear-resistant materials in micro/nanoelectromechanical systems has stimulated the research of friction-reducing and antiwear materials. However, the fabrication of subnanometer-thick films with superlubricating and super wear-resistant properties under ambient conditions remains a huge challenge. Herein, high-quality monolayer (ML) NbSe2 (∼0.8 nm) with ultralow friction and super wear resistance in an atmospheric environment was successfully grown by chemical vapor deposition (CVD) for the first time. Moreover, compared with few-layered (FL) NbSe2, ML NbSe2 has a lower friction coefficient and better wear resistance. On the basis of density function theory (DFT) calculations, the adhesion and the degree of charge transfer between ML NbSe2 and the substrate is larger than that of the topmost layer to the underlying layers of NbSe2 with two or more layers, which can be used to explain that the ML NbSe2 favors ultralow friction and super wear resistance.

Value of 99mTc-MIBI SPECT/CT in distinguishing between parathyroid lesions and nodular goiter. / 99mTc-MIBI SPECT/CTåœ¨ç”²çŠ¶æ—è ºç— ç¶ä¸Žç»“èŠ‚æ€§ç”²çŠ¶è ºè‚¿é‰´åˆ«è¯Šæ–­ä¸­çš„ä»·å€¼.

OBJECTIVES: Hyperfunctioning parathyroid lesions require surgical resection. 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) plays an important role in the diagnosis of parathyroid lesions. Some nodular goiters have a higher uptake of 99mTc-MIBI, which is difficult to distinguish from hyperfunctioning parathyroid lesions. This study aims to explore the value of 99mTc-MIBI SPECT/CT in the differential diagnosis of parathyroid lesions and nodular goiter. METHODS: This study was a retrospective analysis. A total of 68 patients who were diagnosed as parathyroid lesions by 99mTc-MIBI SPECT/CT were enrolled, with a total of 81 lesions. According to the results of pathological examination after surgical resection, the lesions were divided into a parathyroid lesion group (n=69) and a nodular goiter group (n=12). The target maximum radioactivity count (Tmax) of all lesions was measured. The mean radioactivity count of the aortic arch was used as the background mean radioactivity count (Bmean), and the ratio of the Tmax to Bmean was calculated. The difference in Tmax/Bmean between the 2 groups was compared. The minimum, mean, and maximum of CT density in the lesion were measured. The difference of CT density between the 2 groups was compared. The receiver operating characteristic (ROC) curve of patients with parathyroid lesions and patients with nodular goiter was drawn, and the diagnostic efficacy of each CT density value was evaluated. RESULTS: The 99mTc-MIBI radioactive uptake in parathyroid lesions and nodular goiter lesions was significantly concentrated. The CT density values of the 2 lesions were lower than normal thyroid tissue, and the boundary between the 2 lesions and the thyroid was clear or blurred. There was no significant difference in Tmax/Bmean between the 2 groups (P=0.221). The differences in the minimum, mean and maximum of CT density between the 2 groups were statistically significant (all P<0.05). The diagnostic efficiency of maximum of CT density was the best, area under the ROC curve was 0.894 (P<0.001), the cut-off was 91 HU, the sensitivity was 83.3%, and the specificity was 94.2%. CONCLUSIONS: The degree of 99mTc-MIBI radiation uptake in the focus has limited value in differentiating parathyroid lesions from nodular goiter, and the maximum density of CT possesses high diagnostic efficiency.

Impact of microRNA-21-5p on the growth of thyroid cancer cells via targeting the recombinant sclerostin domain containing protein 1. / å¾®RNA-21-5p靶向调控含硬化蛋白域蛋白1å¯¹ç”²çŠ¶è ºç™Œç»†èƒžç”Ÿé•¿çš„å½±å“.

OBJECTIVES: To explore the molecular mechanism for thyroid cancer metastasis via analyzing the role of microRNA (miR)-21-5p and its target gene recombinant sclerostin domain containing protein 1 (SOSTDC1) in thyroid cancer. METHODS: The target miR-21-5p was screened through bioinformatics analysis and cell verification, and the thyroid cancer cell lines was transfected with miR-21-5p inhibitor. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, flow cytometry, and cell scratch test were used to detect the proliferation, apoptosis and migration of thyroid cancer cells in the miR-21-5p inhibitor group and the inhibitor control group, respectively. The luciferase report experiment was used to verify the relationship between miR-21-5p and SOSTDC1, Western blotting was used to detect the expression levels and phosphorylation levels of SOSTDC1,phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt) and mitogen-activated protein kinases (MAPK), extracellular regulated protein kinases (ERK) in thyroid cancer cells. RESULTS: MiR-21-5p was significantly increased in thyroid cancer cells,which was negatively correlated with SOSTDC1 (r=-0.24, P<0.01). The proliferation and migration of thyroid cancer cells in the miR-21-5p inhibitor group was significantly lower than that in the inhibitor control group (both P<0.01), and the apoptosis rate in the miR-21-5p inhibitor group was significantly higher than that in the inhibitor control group (P<0.01).The luciferase report experiment showed that miR-21-5p could target and regulate the expression level of SOSTDC1, and the expression of PI3K in the miR-21-5p inhibitor group was significantly lower than that in the inhibitor control group (P<0.01). There were no significant changes in Akt and ERK1/2 levels, but the phosphorylation levels of Akt and ERK1/2 in the miR-21-5p inhibitor group were significantly lower than those in the inhibitor control group (both P<0.01). CONCLUSIONS: MiR-21-5p in thyroid cancer cells can target the expression of SOSTDC1 and affect the activities of PI3K/Akt and MAPK/ERK, thereby inhibiting the apoptosis of thyroid cancer cells and promoting cell proliferation and migration.

An Overlooked Natural Hydrogen Evolution Pathway: Ni2+ Boosting H2 O Reduction by Fe(OH)2 Oxidation during Low-Temperature Serpentinization.

Natural hydrogen (H2 ) has gained considerable attentions as a renewable energy resource to mitigate the globally increasing environmental concerns. Low-temperature serpentinization (<200 °C) as a typical water-rock reaction is a major source of the natural H2 . However, the reaction mechanism and the controlling step to product H2 remained unclear, which hinders the further utilization of natural H2 . Herein, we demonstrated that the H2 production rate could be determined by the Fe(OH)2 oxidation during low-temperature serpentinization. Moreover, the co-existence of Ni2+ could largely enhance the H2 production kinetics. With the addition of only 1 % Ni2+ , the H2 production rate was remarkably enhanced by about two orders of magnitude at 90 °C. D2 O isotopic experiment and theoretical calculations revealed that the enhanced H2 production kinetics could be attributed to the catalytic role of Ni2+ to promote the reduction of H2 O.

NLRP3 deficiency exacerbates enterovirus infection in mice.

The role for the NOD-like receptor (NLR) P3 inflammasome in enterovirus infection remains controversial. Available data suggest that the NLRP3 inflammasome is protective against enterovirus A71 but detrimental to the host during coxsackievirus B3 (CVB3) infection. CVB3 is a common etiologic agent associated with myocarditis and pancreatitis. Previous findings on the role of NLRP3 in CVB3 were based primarily on indirect evidence. Here, we utilized NLRP3 knockout mice as well as immune and cardiac cells to investigate the direct interplay between CVB3 infection and NLRP3 activation. We demonstrated that NLRP3 knockout mice exhibited more severe disease phenotype after CVB3 infection (significantly higher virus titers), increased myocardial, and pancreatic damage, as well as markedly impaired cardiac function compared to nontransgenic control mice. We further showed that NLRP3 activity was enhanced during early stage of CVB3 infection, as evidenced by increased gene expression and/or secretion of IL-1ß and caspase-1. Finally, we demonstrated that CVB3 inactivates the NLRP3 inflammasome by degrading NLRP3 and its upstream serine/threonine-protein kinase receptor-interacting protein 1/3 via the proteolytic activity of virus-encoded proteinases. Taken together, our results reveal the functional significance of NLRP3 in host antiviral immunity against CVB3 infection and the mechanisms by which CVB3 has evolved to counteract the host defense response.-Wang, C., Fung, G., Deng, H., Jagdeo, J., Mohamud, Y., Xue, Y. C., Jan, E., Hirota, J. A., Luo, H. NLRP3 deficiency exacerbates enterovirus infection in mice.

Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio Predict Severity and Prognosis of Lower Limb Arteriosclerosis Obliterans.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are 2 markers of inflammation, which are associated with worse cardiovascular disease outcomes. Here, we aimed to determine the association between these ratios and disease severity and evaluate predictive validity of the NLR and PLR in lower limb arteriosclerosis obliterans (ASO). METHODS: We evaluated 211 patients with a diagnosis of ASO from January 2016 to December 2018 at Shanghai Jiaotong University Renji Hospital. The NLR and PLR were accessed from routinely drawn peripheral venous blood at the ward of vascular surgery during hospitalization. The association between the NLR and PLR with baseline characteristics, disease severity, and one-year outcomes were determined, respectively. RESULTS: Both the NLR and PLR showed significant values on predicting disease severity. A higher NLR (P = 0.001) and PLR (P < 0.001) were associated with lower ankle-brachial index and worse clinical presentation. Both the NLR and PLR are positively correlated with one-year readmission rate (P < 0.001, P = 0.001, respectively). Both the NLR and PLR also positively correlated with the tissue loss rate and one-year mortality (P = 0.007, P = 0.034, respectively). CONCLUSIONS: The NLR and PLR show a positive association with the severity of lower extremity peripheral artery disease, both higher ratios correlate with poor prognosis, especially, the risk of one-year readmission. A higher NLR also correlates with one-year mortality.

Enteroviral Infection Leads to Transactive Response DNA-Binding Protein 43 Pathology in Vivo.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons in the cerebral cortex, brainstem, and spinal cord, leading to progressive paralysis and eventual death. Approximately 95% of all ALS cases are sporadic without known causes. Enteroviruses have been suspected to play a role in ALS because of their ability to target motor neurons and to cause muscle weakness and paralysis. In vitro enteroviral infection results in cytoplasmic aggregation and cleavage of transactive response DNA binding protein-43, a pathologic hallmark of ALS. However, whether enteroviral infection can induce ALS-like pathologies in vivo remains to be characterized. In this study, neonatal BALB/C mice were intracranially inoculated with either a recombinant coxsackievirus B3 expressing enhanced green fluorescent protein or mock-infected for 2, 5, 10, 30, and 90 days. Histologic and immunohistochemical analysis of brain tissues demonstrated sustained inflammation (microglia and astrogliosis) and lesions in multiple regions of the brain (hippocampus, cerebral cortex, striatum, olfactory bulb, and putamen) in parallel with virus detection as early as 2 days for up to 90 days after infection. Most notably, ALS-like pathologies, including cytoplasmic mislocalization of transactive response DNA binding protein-43, p62-, and ubiquitin-positive inclusions, were observed in the areas of infection. These data provide the first pathologic evidence to support a possible link between enteroviral infection and ALS.

Spatial-temporal variations in the thermal growing degree-days and season under climate warming in China during 1960-2011.

Vegetation growth and phenology are largely regulated by base temperature (Tb) and thermal accumulation. Hence, the growing degree-days (GDD) and growing season (GS) calculated based on Tb have primary effects on terrestrial ecosystems, and could be changed by the significant warming during the last century. By choosing 0, 5, and 10 °C, three key Tb for vegetation growth, the GDD and GS in China during 1960-2011 were developed based on 536 meteorological stations with homogenized daily mean temperatures. Results show that both the GDD and GS showed positive sensitivity to the annual mean temperature. The start of the growing season (SOS) has advanced by 4.86-6.71 days, and the end of the growing season (EOS) has been delayed by 4.32-6.19 days, lengthening the GS by 10.76-11.02 days in China as a whole during 1960-2011, depending on the Tb chosen. Consistently, the GDD has totally increased 218.92-339.40 °C days during the 52 years, with trends more pronounced in those based on a lower Tb. The GDD increase was significant (Mann-Kendall test, p < 0.01) over China except for the north of Southwest China, while the significant GS extension only scattered over China. Whereas the extensions of GS0 and GS5 were dominated by the advance in SOS, the GS10 extension was closely linked to the delay in EOS. Regionally, the GS extension in the eastern monsoon zone and northwest arid/semi-arid zone was driven by the advance in SOS and delay in EOS, respectively. Moreover, each variation has a substantial acceleration mostly in 1987 or 1996, and a speed reduction or even a trend reversal in the early 2000s. Changes in the thermal growing degree-days and season are expected to have great implications for biological phenology, agricultural production, and terrestrial carbon cycle in the future.

Enhanced enteroviral infectivity via viral protease-mediated cleavage of Grb2-associated binder 1.

Coxsackievirus B3 (CVB3), an important human causative pathogen for viral myocarditis, pancreatitis, and meningitis, has evolved different strategies to manipulate the host signaling machinery to ensure successful viral infection. We previously revealed a crucial role for the ERK1/2 signaling pathway in regulating viral infectivity. However, the detail mechanism remains largely unknown. Grb2-associated binder 1 (GAB1) is an important docking protein responsible for intracellular signaling assembly and transduction. In this study, we demonstrated that GAB1 was proteolytically cleaved after CVB3 infection at G175 and G436 by virus-encoded protease 2A(pro), independent of caspase activation. Knockdown of GAB1 resulted in a significant reduction of viral protein expression and virus titers. Moreover, we showed that virus-induced cleavage of GAB1 is beneficial to viral growth as the N-terminal proteolytic product of GAB1 (GAB1-N1-174) further enhances ERK1/2 activation and promotes viral replication. Our results collectively suggest that CVB3 targets host GAB1 to generate a GAB1-N1-174 fragment that enhances viral infectivity, at least in part, via activation of the ERK pathway. The findings in this study suggest a novel mechanism that CVB3 employs to subvert the host signaling and facilitate consequent viral replication.

Dysferlin deficiency confers increased susceptibility to coxsackievirus-induced cardiomyopathy.

Coxsackievirus infection can lead to viral myocarditis and its sequela, dilated cardiomyopathy, which represent major causes of cardiovascular mortality worldwide in children. Yet, the host genetic susceptible factors and the underlying mechanisms by which viral infection damages cardiac function remain to be fully resolved. Dysferlin is a transmembrane protein highly expressed in skeletal and cardiac muscles. In humans, mutations in the dysferlin gene can cause limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Dysferlin deficiency has also been linked to cardiomyopathy. Defective muscle membrane repair has been suggested to be an important mechanism responsible for muscle degeneration in dysferlin-deficient patients and animals. Using both naturally occurring and genetically engineered dysferlin-deficient mice, we demonstrated that loss of dysferlin confers increased susceptibility to coxsackievirus infection and myocardial damage. More interestingly, we found that dysferlin is cleaved following coxsackieviral infection through the proteolytic activity of virally encoded proteinases, suggesting an important mechanism underlying virus-induced cardiac dysfunction. Our results in this study not only identify dysferlin deficiency as a novel host risk factor for viral myocarditis but also reveal a key mechanism by which coxsackievirus infection impairs cardiac function, leading to the development of dilated cardiomyopathy.

Mangiferin suppressed advanced glycation end products (AGEs) through NF-κB deactivation and displayed anti-inflammatory effects in streptozotocin and high fat diet-diabetic cardiomyopathy rats.

Given the importance of the aggregation of advanced glycation end products (AGEs) and cardiac inflammation in the onset and progression of diabetic cardiomyopathy (DCM), our objective in this study was to demonstrate the cardioprotective effect of mangiferin, an antidiabetic and anti-inflammatory agent, on diabetic rat model. The DCM model was established by a high-fat diet and a low dose of streptozotocin. DCM rats were treated orally with mangiferin (20 mg/kg) for 16 weeks. Serum and left ventricular myocardium were collected for determination of inflammatory cytokines. AGEs mRNA and protein expression of nuclear factor kappa B (NF-κB) and receptor for AGEs (RAGE) in myocardium were assayed by real-time PCR and Western blot. ROS levels were measured by dihydroethidium fluorescence staining. NF-κB binding activity was assayed by TransAM NF-κB p65 ELISA kit. Chronic treatment with mangiferin decreased the levels of myocardial enzymes (CK-MB, LDH) and inflammatory mediators (TNF-α, IL-1ß). Meanwhile, NF-κB is inhibited by the reduction of nuclear translocation of p65 subunit, and mangiferin reduced AGE production and decreased the mRNA and protein expression of RAGE in DCM rats. Our data indicated that mangiferin could significantly ameliorate DCM by preventing the release of inflammatory cytokines, and inhibiting ROS accumulation, AGE/RAGE production, and NF-κB nuclear translocation, suggesting that mangiferin treatment might be beneficial in DCM.

Spatio-temporal pattern and the evolution of the distributional dynamics of county-level agricultural economic resilience in China.

Because the complexity of the external environment has put great pressure on the agricultural economy, making it vulnerable, it is necessary to promote a system of resilience in the agricultural economy so that Chinese agriculture can continue to persevere in the face of serious external uncertainties. Therefore, this paper investigates the spatio-temporal pattern and evolution of the distributional dynamics of China's county-level agricultural economic resilience based on 2000-2020 data covering 2,545 counties. The results are as follows: first, from 2000 to 2020, the mean value of China's county-level agricultural economic resilience showed an obvious upward trend, which indicates that China's agricultural economy gradually increased its ability to resist risks and continued to develop in a favourable manner. Specifically, the county-level agricultural economic resilience index of the northeast region grew the most significantly, while the index of county units in the western region was relatively low. Second, the centre of gravity of the spatial distribution of China's agricultural economic resilience gradually migrated to the northwest, showing a dominant direction from northeast to southwest and a tendency to develop from southeast to northwest. Third, the spatial differences in China's agricultural economic resilience generally showed an upward trend, while county-level differences were the main source of the overall differences, followed by inter-provincial differences, inter-municipal differences and inter-regional differences. Additionally, the contribution of county-level differences to the overall differences fluctuated within the range of 54%-58%. Fourth, there is a possibility of localized convergence in China's agricultural economic resilience, which is continuous in spatial effects and has obvious positively correlated spatial effects at different times and in different county spaces.

TCJA-SNN: Temporal-Channel Joint Attention for Spiking Neural Networks.

Spiking neural networks (SNNs) are attracting widespread interest due to their biological plausibility, energy efficiency, and powerful spatiotemporal information representation ability. Given the critical role of attention mechanisms in enhancing neural network performance, the integration of SNNs and attention mechanisms exhibits tremendous potential to deliver energy-efficient and high-performance computing paradigms. In this article, we present a novel temporal-channel joint attention mechanism for SNNs, referred to as TCJA-SNN. The proposed TCJA-SNN framework can effectively assess the significance of spike sequence from both spatial and temporal dimensions. More specifically, our essential technical contribution lies on: 1) we employ the squeeze operation to compress the spike stream into an average matrix. Then, we leverage two local attention mechanisms based on efficient 1-D convolutions to facilitate comprehensive feature extraction at the temporal and channel levels independently and 2) we introduce the cross-convolutional fusion (CCF) layer as a novel approach to model the interdependencies between the temporal and channel scopes. This layer effectively breaks the independence of these two dimensions and enables the interaction between features. Experimental results demonstrate that the proposed TCJA-SNN outperforms the state-of-the-art (SOTA) on all standard static and neuromorphic datasets, including Fashion-MNIST, CIFAR10, CIFAR100, CIFAR10-DVS, N-Caltech 101, and DVS128 Gesture. Furthermore, we effectively apply the TCJA-SNN framework to image generation tasks by leveraging a variation autoencoder. To the best of our knowledge, this study is the first instance where the SNN-attention mechanism has been employed for high-level classification and low-level generation tasks. Our implementation codes are available at https://github.com/ridgerchu/TCJA.

CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice.

Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing levels of HDL-C by inhibition of cholesteryl ester transfer protein (CETP) decreases mortality from intraabdominal polymicrobial sepsis in APOE*3-Leiden.CETP mice. Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden.CETP and APOA1.CETP mice. Mechanistically, CETP inhibition reduced the host proinflammatory response via attenuation of proinflammatory cytokine transcription and release. This effect was dependent on the presence of HDL, leading to attenuation of immune-mediated organ damage. In addition, CETP inhibition promoted monocyte activation in the blood prior to the onset of sepsis, resulting in accelerated macrophage recruitment to the lung and liver. In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.

Rare double heterozygous mutations in antithrombin underlie hereditary thrombophilia in a Chinese family.

VTE is a complex disorder with two main manifestations: DVT and PE. Deficiency of natural anticoagulants plays an important role in the pathogenesis of VTE. Antithrombin (AT) deficiency is one of the most common hereditary thrombophilia in Asia. Subjects with AT deficiency have two mutations in the same allele of the SERPINC1 gene: p.Arg45Gln and p.Ser114Arg (Arg13Gln and Ser82Arg, according to the antithrombin mutation database). DNA sequencing, ELISA (enzyme-linked immuno sorbent assay), plasmid transfection, and homology modeling were performed to study the molecular pathophysiological mechanism of the deficiency. Recombinant expression of these mutations demonstrated a relevant functional effect on the p.Ser114Arg mutation, since it almost abolished the secretion of AT to the conditioned medium and increased intracellular retention, while the p.Arg45Gln mutation had negligible effects. Homology modeling showed that some atoms from Arg114 interfered with the atoms of the ß-strand, the abstract power between Arg45 and S2 was larger than that between Gln45 and S2, and the electrostatic energy (-617.281 to -452.079 K) was the primary contributor to this difference. The functional mutation responsible for the deficiency of this potent anticoagulant p.Ser114Arg probably has conformational consequences on the folding of the protein leading to its intracellular accumulation and impaired secretion.

[Phenotypic detection and structure analysis of a PC missense mutation (Met406Ile) resulted in venous thromboembolism].

OBJECTIVE: To identify the phenotypic detection and structure analysis of a protein C (PC) missense mutation (Met406Ile) resulting in venous thromboembolism. METHODS: Pedigree research was performed for a hereditary PC deficiency pedigree. Chromogenic assay was used for phenotypic diagnosis to detect the AT activity. All 9 exons were amplified by polymerase chain reaction (PCR) and direct sequencing analysis was performed for PCR products. The corresponding mutation sites of family members were detected.Homology modeling was used for reconstructing mutant PC construction. The effects of construction change were analyzed. RESULTS: The PC activities of proband and 4 family members decreased to different extents by 29.7%, 42.2%, 42.4%, 67.3% and 70.7% respectively. Among them, the proband and other three family members carried the same mutation (c.1218G > A, Met406Ile) while another family member had a PC polymorphism (rs1799810). Homology modeling showed that VDW's interaction radius of amino acids decreased after mutation (Met406Ile).In particular, the radius of Gly418:C and Ile406CG2, Gly418:C and Ile406HG23, Leu419:N and Ile406:HG23 decreased to 2.0733å, 1.620 45å and 1.446 52å respectively. Compared with normal PC, the interaction energy of mutant PC rose from -8.504 54 to 1210.04 kal/mol. And the change of VDW interaction energy was significant. CONCLUSION: The mechanism of this pedigree is caused by PROC gene missense mutation on exon 9 (c.1218G > A, Met406Ile). The regional amino acids of mutant PC collide with each other and lead to an instability of PC reconstruction.

[Molecular mechanisms of antithrombin deficiency caused by novel double heterozygous mutations].

OBJECTIVE: To explore the molecular mechanisms of antithrombin (AT) deficiency caused by novel double heterozygous mutations. METHODS: Wild-type and mutant AT cDNA expression plasmids (ATwt, AT-c.134G > A, AT-c.342T > G, AT-c.134G > A and AT-c.342T > G) were transfected into HEK293T cells. Western blot was used to detect the AT:Ag in cell lysates. Homology was used to reestablish 3-D spatial structure of AT. Laser confocal assay was utilized to analyze the distribution of AT in endoplasmic reticulum (ER). RESULTS: Compared to the wild-types, the AT expression of HEK293T cells sharply increased when they were transfected by AT-c.342T > G or AT-c.134G > A and c.342T > G. Homology modeling showed that the mutation (AT-c.342T > G) caused a decreased distance between Arg and surrounding bases as Arg's side chain was significantly longer than Ser's. The mutation of 13th base pair decreases the distance between AT and heparin. Laser confocal assay showed that the AT protein concreted in HEK293T cells when they were transfected by mutant plasmids (AT-c.134G > A and c.342T > G) and aggregated in ER. CONCLUSIONS: The main molecular mechanism of AT deficiency in this pedigree is the disturbed AT secretion as a result of the mutation of AT-c.342T > G.

Assessing and improving active travel around urban hospitals: A case of Xiangya hospital, China.

Since the outbreak of COVID-19, there has been a growing trend toward active travel. However, many cities have not given sufficient attention to active transportation, resulting in inadequate safety measures for pedestrians and cyclists. This issue becomes particularly critical around hospitals, closely associated with COVID-19 and where traffic can be more intricate and hazardous. Hence, there is a pressing need for a quantitative assessment of the active travel environment surrounding hospitals to obtain a practical evaluation and devise improvement strategies. This study constructs an Extenics evaluation model to assess the safety, accessibility, traffic pressure, convenience, and comfort of the active travel environment near Xiangya Hospital. Subsequently, optimization strategies are proposed based on the evaluation outcomes. The evaluation results show high traffic pressure around the hospital during peak hours while the infrastructure is insufficient. A diversion strategy must be developed based on the evaluation findings to address safety concerns. Furthermore, issues such as inadequate non-motorized lanes and accessibility facilities in the area are identified. Correspondingly, improvement strategies tailored to the specific problems of each street are suggested based on the evaluation results. While this research focuses on urban hospitals, it aims to offer valuable insights into evaluating and enhancing active travel environments around large public buildings.

Recent Advances in Application of Polyoxometalates in Lignocellulose Pretreatment and Transformation.

Lignocellulose, composed of cellulose, hemicellulose, and lignin, holds immense promise as a renewable resource for the production of sustainable chemicals and fuels. Unlocking the full potential of lignocellulose requires efficient pretreatment strategies. In this comprehensive review, efforts were taken to survey the latest developments in polyoxometalates (POMs)-assisted pretreatment and conversion of lignocellulosic biomass. An outstanding finding highlighted in this review is that the deformation of the cellulose structure from I to II accompanied by the removal of xylan/lignin through the synergistic effect of ionic liquids (ILs) and POMs resulted in a significant increase in glucose yield and improved cellulose digestibility. Furthermore, successful integration of POMs with deep eutectic solvents (DES) or γ-valerolactone/water (GVL/water) systems has demonstrated efficient lignin removal, opening avenues for advanced biomass utilization. This review not only presents the key findings and novel approaches in POMs-based pretreatment but also addresses the current challenges and prospects for large-scale industrial implementation. By offering a comprehensive assessment of the progress in this field, this review serves as a valuable resource for researchers and industry professionals aiming to harness the potential of lignocellulosic biomass for sustainable chemical and fuel production.

Bimetallic polyoxometalates catalysts for efficient lignin depolymerization: Unlocking valuable aromatic compounds from renewable feedstock.

Lignin, a complex and abundant polymer present in lignocellulosic biomass, holds immense potential as a renewable source for the production of valuable aromatic compounds. However, the efficient depolymerization of lignin into these compounds remains a formidable challenge. Here, we present a promising solution by harnessing polyoxometalates (POMs) catalysts, which exhibit improved catalytic performance and selectivity. We synthesized a series of NixCoy@POMs catalysts (POMs: CsPW or CsPMo) and explored their application in the depolymerization of pine lignin, aiming to investigate the influence of different metal species and doping ratios of POMs on catalytic performance. Through meticulous optimization of reaction conditions, we achieved significant yields of valuable aromatic compounds, including methyl vanillate, vanillin, and 4-hydroxy-3-methoxyacetophenone. Furthermore, the Ni0.75Co0.75@CsPMo catalyst demonstrated exceptional efficacy in catalyzing the cracking process of C-C and/or C-O bonds in a ß-O-4 dimer model compound. Notably, our catalyst exhibited outstanding stability over five cycles, underscoring its suitability as an effective heterogeneous catalyst for cyclic lignin depolymerization. This study sheds light on the potential of POMs-based catalysts for advancing lignin valorization and offers new avenues for sustainable biomass conversion into valuable chemicals.