Unraveling Lattice-Distortion Hardening Mechanisms in High-Entropy Carbides.

Uncovering the hardening mechanisms is of great importance to accelerate the design of superhard high-entropy carbides (HECs). Herein, the hardening mechanisms of HECs by a combination of experiments and first-principles calculations are systematically explored. The equiatomic single-phase 4- to 8-cation HECs (4-8HECs) are successfully fabricated by the two-step approach involving ultrafast high-temperature synthesis and hot-press sintering techniques. The as-fabricated 4-8HEC samples possess fully dense microstructures (relative densities of up to ≈99%), similar grain sizes, clean grain boundaries, and uniform compositions. With the elimination of these morphological properties, the monotonic enhancement of Vickers hardness and nanohardness of the as-fabricated 4-8HEC samples is found to be driven by the aggravation of lattice distortion. Further studies show no evident association between the enhanced hardness of the as-fabricated 4-8HEC samples and other potential indicators, including bond strength, valence electron concentration, electronegativity mismatch, and metallic states. The work unveils the underlying hardening mechanisms of HECs and offers an effective strategy for designing superhard HECs.

Research progress on multiple cell death pathways of podocytes in diabetic kidney disease.

Diabetic kidney disease (DKD) is the main cause of end-stage renal disease, and its clinical manifestations are progressive proteinuria, decreased glomerular filtration rate, and renal failure. The injury and death of glomerular podocytes are the keys to DKD. Currently, a variety of cell death modes have been identified in podocytes, including apoptosis, autophagy, endoplasmic reticulum (ER) stress, pyroptosis, necroptosis, ferroptosis, mitotic catastrophe, etc. The signaling pathways leading to these cell death processes are interconnected and can be activated simultaneously or in parallel. They are essential for cell survival and death that determine the fate of cells. With the deepening of the research on the mechanism of cell death, more and more researchers have devoted their attention to the underlying pathologic research and the drug therapy research of DKD. In this paper, we discussed the podocyte physiologic role and DKD processes. We also provide an overview of the types and specific mechanisms involved in each type of cell death in DKD, as well as related targeted therapy methods and drugs are reviewed. In the last part we discuss the complexity and potential crosstalk between various modes of cell death, which will help improve the understanding of podocyte death and lay a foundation for new and ideal targeted therapy strategies for DKD treatment in the future.

Application of recombinant TGF-ß1 inhibitory peptide to alleviate isoproterenol-induced cardiac fibrosis.

Cardiac fibrosis is a remodeling process of the cardiac interstitium, characterized by abnormal metabolism of the extracellular matrix, excessive accumulation of collagen fibers, and scar tissue hyperplasia. Persistent activation and transdifferentiation into myofibroblasts of cardiac fibroblasts promote the progression of fibrosis. Transforming growth factor-ß1 (TGF-ß1) is a pivotal factor in cardiac fibrosis. Latency-associated peptide (LAP) is essential for activating TGF-ß1 and its binding to the receptor. Thus, interference with TGF-ß1 and the signaling pathways using LAP may attenuate cardiac fibrosis. Recombinant full-length and truncated LAP were previously constructed, expressed, and purified. Their effects on cardiac fibrosis were investigated in isoproterenol (ISO)-induced cardiac fibroblasts (CFs) and C57BL/6 mice. The study showed that LAP and tLAP inhibited ISO-induced CF activation, inflammation, and fibrosis, improved cardiac function, and alleviated myocardial injury in ISO-induced mice. LAP and tLAP alleviated the histopathological alterations and inhibited the elevated expression of inflammatory and fibrosis-related markers in cardiac tissue. In addition, LAP and tLAP decreased the ISO-induced elevated expression of TGF-ß, αvß3, αvß5, p-Smad2, and p-Smad3. The study indicated that LAP and tLAP attenuated ISO-induced cardiac fibrosis via suppressing TGF-ß/Smad pathway. This study may provide a potential approach to alleviate cardiac fibrosis. KEY POINTS: • LAP and tLAP inhibited ISO-induced CF activation, inflammation, and fibrosis. • LAP and tLAP improved cardiac function and alleviated myocardial injury, inflammation, and fibrosis in ISO-induced mice. • LAP and tLAP attenuated cardiac fibrosis via suppressing TGF-ß/Smad pathway.

Recombinant truncated latency-associated peptide alleviates liver fibrosis in vitro and in vivo via inhibition of TGF-ß/Smad pathway.

BACKGROUND: Liver fibrosis is a progressive liver injury response. Transforming growth factor ß1 (TGF-ß1) is oversecreted during liver fibrosis and promotes the development of liver fibrosis. Therapeutic approaches targeting TGF-ß1 and its downstream pathways are essential to inhibit liver fibrosis. The N-terminal latency-associated peptide (LAP) blocks the binding of TGF-ß1 to its receptor. Removal of LAP is critical for the activation of TGF-ß1. Therefore, inhibition of TGF-ß1 and its downstream pathways by LAP may be a potential approach to affect liver fibrosis. METHODS: Truncated LAP (tLAP) plasmids were constructed. Recombinant proteins were purified by Ni affinity chromatography. The effects of LAP and tLAP on liver fibrosis were investigated in TGF-ß1-induced HSC-T6 cells, AML12 cells and CCl4-induced liver fibrosis mice by real time cellular analysis (RTCA), western blot, real-time quantitative PCR (RT-qPCR), immunofluorescence and pathological staining. RESULTS: LAP and tLAP could inhibit TGF-ß1-induced AML12 cells inflammation, apoptosis and EMT, and could inhibit TGF-ß1-induced HSC-T6 cells proliferation and fibrosis. LAP and tLAP could attenuate the pathological changes of liver fibrosis and inhibit the expression of fibrosis-related proteins and mRNAs in CCl4-induced liver fibrosis mice. CONCLUSION: LAP and tLAP could alleviate liver fibrosis in vitro and in vivo via inhibition of TGF-ß/Smad pathway. TLAP has higher expression level and more effective anti-fibrosis activity compared to LAP. This study may provide new ideas for the treatment of liver fibrosis.

Neutralizing Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in Coronavirus Disease 2019 Inpatients and Convalescent Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific antiviral treatments or vaccines. There is an urgent need for exploring the neutralizing antibodies from patients with different clinical characteristics. METHODS: A total of 117 blood samples were collected from 70 COVID-19 inpatients and convalescent patients. Antibodies were determined with a modified cytopathogenic neutralization assay (NA) based on live severe acute respiratory syndrome coronavirus 2 and enzyme-linked immunosorbent assay (ELISA). The dynamics of neutralizing antibody levels at different time points with different clinical characteristics were analyzed. RESULTS: The seropositivity rate reached up to 100.0% within 20 days since onset, and remained 100.0% till days 41-53. The total geometric mean titer was 1:163.7 (95% confidence interval [CI], 128.5-208.6) by NA and 1:12 441.7 (95% CI, 9754.5-15 869.2) by ELISA. The antibody level by NA and ELISA peaked on days 31-40 since onset, and then decreased slightly. In multivariate generalized estimating equation analysis, patients aged 31-45, 46-60, and 61-84 years had a higher neutralizing antibody level than those aged 16-30 years (ß = 1.0470, P = .0125; ß = 1.0613, P = .0307; ß = 1.3713, P = .0020). Patients with a worse clinical classification had a higher neutralizing antibody titer (ß = 0.4639, P = .0227). CONCLUSIONS: The neutralizing antibodies were detected even at the early stage of disease, and a significant response was shown in convalescent patients.

Enterovirus D68 in a 6-year-old acute flaccid myelitis case in China, 2018: a case report.

BACKGROUND: Acute flaccid myelitis (AFM) are reported to be associated with enterovirus D68 infection. Though an increasing number of AFM cases were reported with EV-D68 infection in the US, few such cases have been found in China. CASE PRESENTATION: A 6-year-old boy presented with acute flaccid myelitis (AFM) involving left arm after fever and respiratory symptoms for 6 days. Computed Tomography (CT) revealed inflammation in both lungs and magnetic resonance imaging (MRI) of the brain and spine showed swelling in the left frontal lobe and brain stem. The patient was diagnosed with meningomyelitis. EV-D68 was detected from pharyngeal samples 36 days after the onset of the disease. CONCLUSION: We report the first EV-D68 infection in case of AFM in mainland China. AFM surveillance systems is recommended to be established in China to guide diagnosis, case reporting, and specimen collection and testing for better understanding its etiologies.

FGF1 inhibits H2O2-induced mitochondrion-dependent apoptosis in H9c2 cells.

The goal of this research was to reveal the protective effect and mechanism of fibroblast growth factor-1 (FGF1) on oxidative stress injury of H9c2 cells induced by hydrogen peroxide (H2O2). The effects of various concentrations of H2O2 and FGF1 on the activity of H9c2 cells were analyzed by Real Time Cell Analysis (RTCA). The content of ROS, calcium ion, mitochondrial membrane potential and apoptosis were detected by fluorescence probe, the mRNA expression of Bcl-2, Bax and Caspase-3 were detected by real-time PCR to evaluate whether FGF1 has ability to resist the apoptosis of cardiomyocytes caused by oxidative damage. The results showed that the proliferation of H9c2 cells could be inhibited after being treated with 200 µM H2O2 for 12 h, and 100 µg/ml FGF1 could increase the proliferation rate of H9c2 cells, mitochondrial membrane potential and the mRNA expression of Bcl-2, and reduce the ROS accumulation, the level of apoptosis, the content of intracellular calcium and the mRNA expression of Bax and Caspase-3 caused by H2O2. The results showed that FGF1 could regulate oxidative stress by improving mitochondrial function and inhibit the H2O2-induced apoptosis in H9c2 cells.

Alteration in microRNA-25 expression regulate cardiac function via renin secretion.

Heart failure arises from diverse cardiovascular diseases, including hypertension, ischemic disease and atherosclerosis, valvular insufficiency, myocarditis, and contractile protein mutations. MicroRNAs are dysregulated in heart failure, but identification of the specific microRNAs involved remains incomplete. Here, we evaluate miR-25 expression in the peripheral blood from healthy, dilated cardiomyopathy (DCM), remote infarct (OMI), hypertensive heart disease (HHD), and HHD resulting in heart failure (HHDF) using q-PCR. Interestingly, we discovered miR-25 expression in humans is initially decreased at the onset of heart failure but is later increased in end-stage heart failure. We also show that overexpression of miR-25 in normal mice causes cardiomyocyte fibrosis and apoptosis. However, inhibition of miR-25 in normal mice led to activate renin-angiotensin system (RAS) and high blood pressure, mild heart dilation. Notably, the miR-25 cluster knock-out mice was also characterized high blood pressure and no obvious cardiac function alteration. RNA sequencing showed the alteration of miR-25 target genes in angomir-treated mice, including the renin secretion signal related gene. In vitro, cotransfection with the miR-25 antagomir repressed luciferase activity from a reporter construct containing the Pde3a and Cacnalc untranslated region. In summary, miR-25 expression during different stages of heart disease, offers a new perspective for the role of miR-25 function in heart failure.

The dipeptidyl peptidase-4 inhibitor sitagliptin ameliorates renal injury in type 1 diabetic mice via inhibiting the TGF-ß/Smad signal pathway.

Diabetic nephropathy (DN) is a common cause of end-stage kidney disease (ESKD) all over the world. Sitagliptin, an inhibitor of DPP-IV plays a beneficial role in type 2 diabetic nephropathy. The purpose of this study was to explore the effect and mechanism of sitagliptin on renal injury in type 1 diabetic mice. Streptozotocin (STZ) induced type 1 diabetic mice were treated with oral administration of sitagliptin (15 mg/kg/ day) for 4 weeks. The results showed that sitagliptin treatment did not change the levels of blood glucose in STZ induced type 1 diabetic mice. Sitagliptin attenuates diabetic nephropathy by significantly inhibiting 24 h proteinuria, renal injury and fibrosis. Sitagliptin can inhibit the expression level of TGF-ß1 and the other related fibrosis factors in renal tissue of type 1 diabetic mice while delaying the progression of type 1 diabetic nephropathy. These results indicated that sitagliptin treatment is potentially a new strategy for treating type 1 diabetic nephropathy.

Preparation and evaluation of anti-renal fibrosis activity of novel truncated TGF-ß receptor type II.

Production of excessive transforming growth factor-beta 1 (TGF-ß1) with elevated TGF-ß1 activity has been implicated in renal fibrosis via renal epithelial cells activation and collagen deposition. As such, attenuating the binding of TGF-ß1 to its receptor TGF-beta receptor type II (TGF-ßRII) in TGF-ß1-dependent signaling is an attractive target for the control of renal fibrosis. Here, we verified the interaction between novel truncated human TGF-ßRII (thTßRII, Thr23-Gln166) and TGF-ß1, prepared thTßRII in Escherichia coli, and assessed the effects of thTßRII on TGF-ß1-induced human kidney epithelial cells (HK-2) and unilateral ureteral obstruction (UUO) model of renal fibrosis. Our data showed that thTßRII accounted for up to 20% of the total protein and 40% of the inclusion bodies of whole cell lysates under the optimal conditions (0.8 mM IPTG and 25°C for 6 H). Most of the expressed protein in inclusion body was refolded by dialysis refolding procedures and purified by Ni2+ -IDA affinity chromatography. Furthermore, thTßRII decreased type I collagen and α-smooth muscle actin protein expression in TGF-ß1-induced HK-2 cells, and ameliorated kidney morphology and fibrotic responses in fibrosis animal. These findings indicate that thTßRII holds great promise for developing new treatments for renal fibrosis.

11ß-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Development by Lentiviral Screening Based on Computational Modeling.

In this study, rat and human 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) have been cloned by lentiviral transduction and expressed by CHO-K1 cells. The results showed that recombinant plasmids contained R11bhsd1 or H11bhsd1 have been constructed, which is consistent with the gene bank respectively. A clone cell was selected with G418 and cultivated to express 11ß-HSD1. 11ß-HSD1 catalytic activity of rat and human were 99.5 and 98.7%, respectively, determined by scanning radiometer. And the cloned CHO-K1 cells expressed the protein of 11ß-HSD1 in a long-term and stable manner, which makes it suitable for screening 11ß-HSD1 inhibitor. The three-dimensional structure of 11ß-HSD1 was used for studying the interaction between inhibitor and enzyme by the binding poses predicted by AutoDock and LeDock software. The docking results revealed that compound 8 forms 2 hydrogen bonds with the residues of Gly-216 and Ile-218 in 11ß-HSD1, that is to say compound 8 maybe a good 11ß-HSD1 inhibitor. Moreover, C57BL/6 mice with R11bHsd1 overexpression had a higher body weight, glucose, total cholesterol, and triglyceride levels compared to the mice treated with an empty viral vector. The results might provide a beneficial foundation for selecting inhibitors of 11ß-HSD1 or for researching drug candidate mechanisms.

miR-23b promotes cutaneous wound healing through inhibition of the inflammatory responses by targeting ASK1.

Wound healing is a complicated event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. MicroRNAs (miRNAs) have been proved to play an important role in the healing process of skin trauma, and alteration of specific miRNA expression during different phases may be associated with abnormal wound healing. In this study, we determined the variation of miR-23b expression after trauma in normal mice and in cultured cells exposed to lipopolysaccharide. We further demonstrated that excessive miR-23b could significantly accelerate wound healing in vivo. Up-regulation of miR-23b decreases infiltration of inflammatory cells, as evidenced by pathologic staining. Meanwhile, miR-23b could significantly inhibit the expression of pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-6, and Ccl2, and significantly increase anti-inflammatory factor IL-10. Furthermore, miR-23b could also promote α-SMA expression in a fiber pattern and increase the expression of Col1a1 and Col3a1. Importantly, we also showed that miR-23b could inhibit inflammation to promote wound healing by targeting apoptotic signal-regulating kinase 1 (ASK1). Notably, knockdown of ASK1 could reduce inflammation factor expression in vitro. Together, our data reveal that miR-23b is a potent therapeutic agent for cutaneous wound healing that shortens the period of inflammatory responses and promotes keratinocyte migration for the re-epithelialization of wound sites.

Variations in MicroRNA-25 Expression Influence the Severity of Diabetic Kidney Disease.

Diabetic nephropathy is characterized by persistent albuminuria, progressive decline in GFR, and secondary hypertension. MicroRNAs are dysregulated in diabetic nephropathy, but identification of the specific microRNAs involved remains incomplete. Here, we show that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of microRNA-25 (miR-25) compared with those of their nondiabetic counterparts. Furthermore, treatment with high glucose decreased the expression of miR-25 in cultured kidney cells. In db/db mice, systemic administration of an miR-25 agomir repressed glomerular fibrosis and reduced high BP. Notably, knockdown of miR-25 in normal mice by systemic administration of an miR-25 antagomir resulted in increased proteinuria, extracellular matrix accumulation, podocyte foot process effacement, and hypertension with renin-angiotensin system activation. However, excessive miR-25 did not cause kidney dysfunction in wild-type mice. RNA sequencing showed the alteration of miR-25 target genes in antagomir-treated mice, including the Ras-related gene CDC42. In vitro, cotransfection with the miR-25 antagomir repressed luciferase activity from a reporter construct containing the CDC42 3' untranslated region. In conclusion, these results reveal a role for miR-25 in diabetic nephropathy and indicate a potential novel therapeutic target for this disease.

Using a community based survey of healthcare seeking behavior to estimate the actual magnitude of influenza among adults in Beijing during 2013-2014 season.

BACKGROUND: Due to a lack of survey of health care seeking behavior for influenza, the actual magnitude of influenza in Beijing of China has not been well described. METHODS: During 2013-2014 influenza season, two cross-sectional household surveys were carried out respectively during the epidemic and non-epidemic season of influenza. A structured survey was undertaken with individuals who were ≥18 years selected by a multistage random sampling method in the study. Health care seeking behaviors were then examined to estimate the actual case number of influenza, using a multiplier model. RESULTS: A total of 14,665 adults were interviewed. 61.9% of ILI cases consulted a physician. The consultation rate during epidemic period is higher than that during non-epidemic period (67.9% vs. 52.3%). Similarly, the proportion of healthcare usage of general hospital during epidemic period is higher than that was during non-epidemic period (27.1% vs. 19.0%, p = 0.008). Lack of insurance and education reduced healthcare seeking significantly in this study. It was estimated that there were 379,767 (90% CI = [281,934, 526,565]) confirmed cases of influenza amongst adults in Beijing, during 2013-2014 influenza season, with an incidence rate of 2.0%. CONCLUSIONS: The surveillance system for ILI and virological data has the potential to provide baseline case number to estimate the actual annual magnitude of influenza. Given the changes in healthcare seeking behavior over time, sentinel surveillance on healthcare seeking behavior are required to be established for better estimate of the true case number of influenza.

MicroRNA-23b Targets Ras GTPase-Activating Protein SH3 Domain-Binding Protein 2 to Alleviate Fibrosis and Albuminuria in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a frequent and severe complication of diabetes that is structurally characterized by glomerular basement membrane thickening, extracellular matrix accumulation, and destabilization of podocyte foot processes. MicroRNAs (miRNAs) are dysregulated in DN, but identification of the specific miRs involved remains incomplete. Here, we confirm that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of miR-23b compared with those of their nondiabetic counterparts. Furthermore, exposure to high glucose downregulated miR-23b in cultured kidney cells. In contrast, renal expression of Ras GTPase-activating protein SH3 domain-binding protein 2 (G3BP2), a putative miR-23b target, increased in DN. In vitro, overexpression of miR-23b decreased, and inhibition of miR-23b increased, G3BP2 expression levels. Bioinformatics analysis also revealed p53 binding sites in the miR-23b promoter; in vitro inhibition of p53 or the upstream p38 mitogen-activated protein kinase (p38MAPK) upregulated miR-23b expression in high-glucose conditions. In turn, inhibition of G3BP2 or overexpression of miR-23b downregulated p53 and p38MAPK expression in high-glucose conditions. In vivo, overexpression of miR-23b or inhibition of p53 in db/db mice reversed hyperalbuminuria and kidney fibrosis, whereas miR-23b antagomir treatment promoted renal fibrosis and increased albuminuria in wild-type mice. These data suggest that hyperglycemia regulates pathogenic processes in DN through an miR-23b/G3BP2 feedback circuit involving p38MAPK and p53. In conclusion, these results reveal a role for miR-23b in DN and indicate a novel potential therapeutic target.

Characterizing the epidemiology, virology, and clinical features of influenza in China's first severe acute respiratory infection sentinel surveillance system, February 2011-October 2013.

BACKGROUND: After the 2009 influenza A(H1N1)pdm09 pandemic, China established its first severe acute respiratory infections (SARI) sentinel surveillance system. METHODS: We analyzed data from SARI cases in 10 hospitals in 10 provinces in China from February 2011 to October 2013. RESULTS: Among 5,644 SARI cases, 330 (6%) were influenza-positive. Among these, 62% were influenza A and 38% were influenza B. Compared with influenza-negative cases, influenza-positive SARI cases had a higher median age (20.0 years vs.11.0, p=0.003) and were more likely to have at least one underlying chronic medical condition (age adjusted percent: 28% vs. 25%, p<0.001). The types/subtypes of dominant strains identified by SARI surveillance was almost always among dominant strains identified by the influenza like illness (ILI) surveillance system and influenza activity in both systems peaked at the same time. CONCLUSIONS: Data from China's first SARI sentinel surveillance system suggest that types/subtypes of circulating influenza strains and epidemic trends among SARI cases were similar to those among ILI cases.

[Morphology of Hypertrophic Scar Tissues and Expressions of Vascular Endothelial Growth Factor and Transforming Growth Factor Beta Activated Kinase 1 in These Tissues].

OBJECTIVE: To observe the morphology of hypertrophic scar tissue and explore the expressions and distribution of vascular endothelial growth factor (VEGF) and transforming growth factor beta activated kinase 1(TAK1 )in these tissues. METHOD: Hematoxylin-eosin staining, Masson staining,immunofluorescence,and real-time polymerase chain reaction were used to detect the localization and expression of VEGF and TAK1 in 15 hypertrophic scar tissues and 10 normal skin tissues. RESULTS: Morphological observation showed that the dermal fibroblasts in hypertrophic scar were disorderly and densely arranged (compared to the normal skin). Immunofluorescence displayed that the expressions of VEGF and TAK1 in hypertrophic scar tissue were higher than in normal skin tissues. Real-time polymerase chain reaction showed the mRNA expressions of both VEGF and TAK1 were significantly higher in hypertrophic scar tissue than in normal tissue (P<0.01, P<0.05,respectively). CONCLUSIONS: Hypertrophic scar tissue has higher collagen fibrosis degree and higher TAK1 and VEGF expressions than the normal skin. VEGF and TAK1 can be used as the reference indicators for the diagnosis and differential diagnosis of hypertrophic scar and serve as new therapeutic targets.

[Study of Pregnancy Exposure to PFOS on Reproductive Toxicities and Mechanism in Male Offspring Rats].

OBJECTIVE: To explore the effects of testosterone synthesis in adult leydig cell (ALC) of male rats exposed by perfluorooctane sulfonate (PFOS) during pregnancy. METHODS: At gestations 12 day, the pregnant rats were exposed to PFOS (5 mg/kg, PFOS group) or 0.5% Tween (control group) by gavage, once a day for 8 consecutive days. On postnatal day (PND) 70, several indexes of male offspring rats were measured including body mass, testicular coefficient, sperm count, serum testosterone concentration. The mRNA levels of ALC associated with testosterone synthesis were detected by real-time quantitative RT-PCR. RESULTS: The result showed that sperm count and serum testosterone concentration decreased in male offspring rats of PFOS group (P < 0.05), and body mass was significantly lower (P < 0.001). The expression of steroidogenic acute regulatory factor (Star), scavenger receptor class B type 1 (Scarb1), Cyp11a1 (coding gene of cytochrome P450 side chain cleavage) and Hsd17b3 (coding gene of 17ß-hydroxysteroid dehydrogenase) were down regulated (P < 0.05), no significant statistical difference was observed on the mRNA level of insulin-like growth factor-1 (Igf1) and insulin-like factor 3 (Insl3). CONCLUSION: Gestational exposure to PFOS can inhibit the mRNA levels associated with testosterone synthesis, and decrease the ability of testosterone synthesis in ALC of male offspring rats.

High-level expression and characterization of bioactive human truncated variant of hepatocyte growth factor in Escherichia coli.

Hepatocyte growth factor (HGF) is an effective anti-fibrotic factor because of its bioactivity in inhibiting fibrosis-related proteins in the development of hepatic fibrosis. However, high-level production of bioactive mature form HGF is difficult because of its complex structure. Here, we report a non-fusion protein expression system to obtain truncated variant of N-terminal hairpin and first kringle domains of HGF (tvNK1) in Escherichia coli to determine its anti-fibrotic effects on hepatic stellate cells (HSCs). Under the selected conditions of cultivation and isopropyl-ß-D-1-thiogalactopyranoside induction, the expression level of tvNK1 accounted for approximately 65 % of the total cellular protein and 50 % of fusion protein in the supernatant of whole cell lysates. The recombinant protein could be purified in one step with Ni(2+)-affinity chromatograph. Finally, about 65 mg recombinant tvNK1 was obtained from 1 l fermentation culture with no <95 % purity. In vitro, the final purified tvNK1 was shown to inhibit the proliferation of HSCs and decrease the mRNA and protein expression levels of fibrosis-related COL1A1 and α-smooth muscle actin genes.

Ultrastrong and High Thermal Insulating Porous High-Entropy Ceramics up to 2000 °C.

High mechanical load-carrying capability and thermal insulating performance are crucial to thermal-insulation materials under extreme conditions. However, these features are often difficult to achieve simultaneously in conventional porous ceramics. Here, for the first time, it is reported a multiscale structure design and fast fabrication of 9-cation porous high-entropy diboride ceramics via an ultrafast high-temperature synthesis technique that can lead to exceptional mechanical load-bearing capability and high thermal insulation performance. With the construction of multiscale structures involving ultrafine pores at the microscale, high-quality interfaces between building blocks at the nanoscale, and severe lattice distortion at the atomic scale, the materials with an ≈50% porosity exhibit an ultrahigh compressive strength of up to ≈337 MPa at room temperature and a thermal conductivity as low as ≈0.76 W m-1 K-1. More importantly, they demonstrate exceptional thermal stability, with merely ≈2.4% volume shrinkage after 2000 °C annealing. They also show an ultrahigh compressive strength of ≈690 MPa up to 2000 °C, displaying a ductile compressive behavior. The excellent mechanical and thermal insulating properties offer an attractive material for reliable thermal insulation under extreme conditions.