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Presently, there have been some limitations in most of methods to determine poly (γ-glutamic acid) (γ-PGA) content because of many impurities in test specimens. It is necessary to establish a rapid and accurate method to quantify γ-PGA content. In this work, γ-PGA and some impurities commonly seen in fermented broth like glucose, glutamic acid and proteins were used to complex with copper ions. The results show that only γ-PGA can make copper ion precipitated, which content linearly correlates with the precipitate amount. From the study on the validity of the method, it is found that the accuracy and precision are 95.82% and 99.29%, much higher than the ones of method UV and weighing. Therefore, the method via the complexation of copper ion will be popularized to determine γ-PGA content in crude biological samples.

The dissolution of cellulose is a critical step for the efficient utilization of this renewable resource as a starting material for high value-added chemical and biofuel production. In this study, three aprotic solvents were chosen to couple with three ionic liquids (ILs) as binary solvent systems for cellulose dissolution. The percentage of dissolved cellulose of each IL/co-solvent was evaluated and the crystallinity index (CrI) of the undissolved cellulose residues after dissolution were investigated by XRD. Dimethyl sulfoxide exhibited the most effective synergistic interaction with the ILs among three co-solvents for cellulose dissolution. In general, the higher percentage of dissolved cellulose of the IL/co-solvent binary system, the lower CrI value of the undissolved cellulose residue after dissolution. In addition, the dissolution of cellulosic materials with different crystallinity and degree of polymerization indicated that the crystallinity of a cellulosic material played a more dominating role than degree of polymerization in its dissolution process. The hydrogen bond basicity (β value) of selected IL/co-solvent binary system was also calculated. The results showed that the β value of a binary IL/co-solvent system exhibited different trend than neat IL in terms of the cellulose dissolution ability, which should be attributed to the co-solvent effect.

Immune activation at the maternal-fetal interface is a main pathogenic factor of preeclampsia (PE). Neutrophils (PMNs) are activated in PE patients, but the mechanism and consequences of PMN activation need to be further explored. Here, we demonstrated that interleukin-32 (IL-32) expression was significantly upregulated in syncytiotrophoblasts (STBs) and that IL-32β was the major isoform with increased expression in the placenta of severe PE (sPE) patients. Furthermore, the level of IL-32 expression in the placenta was correlated with its level in the serum of sPE patients, indicating that IL-32 in the serum is derived mainly from the placenta. Then, in vitro experiments showed that IL-32β could highly activate PMNs and that these IL-32β-activated PMNs were better able to adhere to endothelial cells (HUVECs) and enhance the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) in HUVECs, which could be reversed by preincubation with the NADPH oxidase inhibitor VAS 2870. In addition, we showed that IL-32β mainly activated PMNs by binding to proteinase 3. Finally, IL-32β administration induced a PE-like phenotype in a pregnant mouse model. This study provides evidence of the involvement of IL-32β in the pathogenesis of PE.

Mitochondria-associated Endoplasmic Reticulum (ER) Membranes (MAMs) are the cellular structures that connect the ER and mitochondria and mediate communication between these two organelles. MAMs have been demonstrated to be involved in calcium signaling, lipid transfer, mitochondrial dynamic change, mitophagy, and the ER stress response. In addition, MAMs are critical for metabolic regulation, and their dysfunction has been reported to be associated with metabolic syndrome, including the downregulation of insulin signaling and the accelerated progression of hyperlipidemia, obesity, and hypertension. This review covers the roles of MAMs in regulating insulin sensitivity and the molecular mechanism underlying MAM-regulated cellular metabolism and reveals the potential of MAMs as a therapeutic target in treating metabolic syndrome.

Preeclampsia (PE) is a pregnancy-related syndrome characterized by new-onset hypertension and proteinuria after gestational 20 weeks. Oxidative stress, resulting from the imbalance between the production of oxidants and antioxidants in placentas, is recognized as a key pathology of PE. To date, the molecules that regulate antioxidants production remain unclear. CD151, a member of tetraspanins, is an important regulator of many physiological functions. However, the function of CD151 in oxidative stress and its association with pregnancy-related complications are currently unknown. In the present study, we have demonstrated that CD151 was a key regulator of antioxidants in placentas. Compared with the placentas of the controls, the placentas of PE patients exhibited decreased CD151 expression accompanying with decreased antioxidant gene expression (HO-1, NQO-1, GCLC and SOD-1). In vitro, overexpression of CD151 in trophoblast cells could enhance HO-1, NQO-1, GCLC and SOD-1 expression but downregulation of CD151 decreased those antioxidant genes expression, which indicates CD151 is the upstream of antioxidants. Importantly, the phenotype of PE (hypertension and proteinuria) was mimicked in the downregulating CD151 induced mouse model. Moreover, the beneficial effect of CD151 in trophoblast cells was hindered when ERK and Nrf2 signaling were blocked. Overall, our results revealed CD151 might be a new target for PE treatment.

Increasing the exposed active sites is a pursuit of great importance for electrocatalysis. Here, an oxygen reduction reaction (ORR) electrocatalyst of palladium–copper (Pd–Cu) bimetallic nanopartic...

In comparison with lithium-ion batteries, sodium-ion batteries (SIBs) have been proposed as an alternative for large-scale energy storage. However, finding an anode material that can overcome the sluggish electrochemical reaction kinetics and fast capacity fading caused by large volume expansion during cycling is problematic. In this study, the intercalation technique for nitrogen-doped carbon layers is implemented for the molybdenum disulfide (MoS2/NC) structure to improve the rate and cycling stability of SIBs by increasing the diffusion rate of sodium ions and mitigating excessive volume structural expansion. The as-synthesized MoS2/NC anode has a high discharge specific capacity of 546 mA h g-1 at 1 A g-1 after 160 cycles, as well as a high rate and stable cycle performance of 406 mA h g-1 at 10 A g-1 after 1000 cycles. Upon coupling with a high-voltage Na3V2(PO4)2O2F cathode, the sodium-ion full battery displays high specific energies of 78.57 W h kg-1 and 49.70 W h kg-1 at specific powers of 193.76 W kg-1 and 3756.80 W kg-1, respectively, with commercialization potential demonstrated.

Herein, a kind of donor–acceptor-conjugated microporous polymer (D–A CMP), poly(triphenylamine–benzothiadiazole) denoted as TPABT, was introduced to synthesize a novel organic–inorganic heterojunction photocatalyst with TiO2 by in situ polycondensation. Resultant TPABT/TiO2 composites were used to photodegrade bisphenol A (BPA) under visible light. Results indicated that the TPABT/TiO2 composite with a mass ratio of TPABT to TiO2 of 10 : 100 (labeled as 10-TPABT/TiO2) showed optimum photocatalytic activity, 8 and 4 times that of pure TiO2 and TPABT, respectively. Systematic characterizations revealed that the incorporation of TPABT caused the generation of oxygen vacancies on TiO2, which improved the visible light responsiveness of TiO2. Moreover, EIS (electrochemical impedance spectroscopy), photocurrent response and PL emission spectra suggested that 10-TPABT/TiO2 composites exhibited optimum activity than TPABT and TiO2. Moreover, detailed investigations indicated that the improvement in the photoactivity of TPABT/TiO2 contributed to the formation of a Z-scheme heterojunction, which enhanced the charge transfer from TPABT to TiO2. This work provides some interesting ideas for enhancing the photocatalytic activity of TiO2 and exploiting efficient heterojunction photocatalysts based on CMPs for pollutant degradation.

Renal tubulointerstitial fibrosis (TIF) is a common pathological feature of aristolochic acid (AA) nephropathy (AAN). G2/M arrest of proximal tubular cells (PTCs) is implicated in renal fibrosis of AAN, but the upstream regulatory molecule remains unknown. Hypoxia inducible factor-1α (HIF-1α) promotes renal fibrosis in kidney disease, but the role of HIF-1α in AAN is unclear. Evidence shows that HIF-1α and p21, a known inducer of cellular G2/M arrest, are closely related to each other. To investigate the role of HIF-1α in renal fibrosis of AAN and its effects on p21 expression and PTCs G2/M arrest, mice with HIF-1α gene knockout PTCs (PT-HIF-1α-KO) were generated, and AAN was induced by AA. In vitro tests were conducted on the human PTCs line HK-2 and primary mouse PTCs. HIF-1α and p21 expression, fibrogenesis, and G2/M arrest of PTCs were determined. Results showed that HIF-1α was upregulated in the kidneys of wild-type (WT) AAN mice, accompanied by p21 upregulation, PTCs G2/M arrest and renal fibrosis, and these alterations were reversed in PT-HIF-1α-KO AAN mice. Similar results were observed in HK-2 cells and were further confirmed in primary PTCs from PT-HIF-1α-KO and WT mice. Inhibiting p21 in HK-2 cells and primary PTCs did not change the expression of HIF-1α, but G2/M arrest and fibrogenesis were reduced. These data indicate that HIF-1α plays a key role in renal fibrosis in AAN by inducing PTCs G2/M arrest modulated through p21. HIF-1α may serve as a potential therapeutic target for AAN.

Pt is the ideal anode catalyst in fuel cells. In this paper, in order to increase the utilization of Pt, the PtAu nanowire networks (NWNs) with ultralow content of Pt are fabricated by a simple silicon monoxide (SiO) reduction method without any capping agent. PtAu NWNs supported on carbon black with Pt content of 1 wt% (Pt0.05Au NWNs) are employed as catalysts for formic acid oxidation (FAO) and methanol oxidation reaction (MOR), whose mass activities are as high as 4998.9 and 2282.3 mA∙mgPt−1, respectively. The network structure facilitates the electron transfer and increases the stability of the catalysts. The PtAu composite experiences compressive lattice strain as confirmed by X-ray powder diffraction (XRD). The Pt0.05Au NWNs catalyst with low Pt content results in the largest strain variation compared with PtAu composited of other ratios, which may downshift the d-band center of Pt and lead to the higher electrocatalytic activity in oxidation reaction.

Anthropogenic aerosols (AAs) induce global and regional tropospheric circulation adjustments due to the radiative energy perturbations. The overall cooling effects of AA, which mask a portion of global warming, have been the subject of many studies but still have large uncertainty. The interhemispheric contrast in AA forcing has also been demonstrated to induce a major shift in atmospheric circulation. However, the zonal redistribution of AA emissions since start of the 20th century, with a notable decline in the Western Hemisphere (North America and Europe) and a continuous increase in the Eastern Hemisphere (South Asia and East Asia), has received less attention. Here we utilize four sets of single-model initial-condition large-ensemble simulations with various combinations of external forcings to quantify the radiative and circulation responses due to the spatial redistribution of AA forcing during 1980–2020. In particular, we focus on the distinct climate responses due to fossil-fuel-related (FF) aerosols emitted from the Western Hemisphere (WH) versus the Eastern Hemisphere (EH). The zonal (west to east) redistribution of FF aerosol emission since the 1980s leads to a weakening negative radiative forcing over the WH mid-to-high latitudes and an enhancing negative radiative forcing over the EH at lower latitudes. Overall, the FF aerosol leads to a northward shift of the Hadley cell and an equatorward shift of the Northern Hemisphere (NH) jet stream. Here, two sets of regional FF simulations (Fix_EastFF1920 and Fix_WestFF1920) are performed to separate the roles of zonally asymmetric aerosol forcings. We find that the WH aerosol forcing, located in the extratropics, dominates the northward shift of the Hadley cell by inducing an interhemispheric imbalance in radiative forcing. On the other hand, the EH aerosol forcing, located closer to the tropics, dominates the equatorward shift of the NH jet stream. The consistent relationship between the jet stream shift and the top-of-atmosphere net solar flux (FSNTOA) gradient suggests that the latter serves as a rule-of-thumb guidance for the expected shift of the NH jet stream. The surface effect of EH aerosol forcing (mainly from low- to midlatitudes) is confined more locally and only induces weak warming over the northeastern Pacific and North Atlantic. In contrast, the WH aerosol reduction leads to a large-scale warming over NH mid-to-high latitudes that largely offsets the cooling over the northeastern Pacific due to EH aerosols. The simulated competing roles of regional aerosol forcings in driving atmospheric circulation and surface temperature responses during the recent decades highlight the importance of considering zonally asymmetric forcings (west to east) and also their meridional locations within the NH (tropical vs. extratropical).

Nod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling and activating the inflammasome complex. Closely related sensor proteins NLRP1 and CARD8 undergo unique auto-proteolysis-dependent activation and are implicated in auto-inflammatory diseases; however, their mechanisms of activation are not understood. Here we report the structural basis of how the activating domains (FIINDUPA-CARD) of NLRP1 and CARD8 self-oligomerize to assemble distinct inflammasome complexes. Recombinant FIINDUPA-CARD of NLRP1 forms a two-layered filament, with an inner core of oligomerized CARD surrounded by an outer ring of FIINDUPA. Biochemically, self-assembled NLRP1-CARD filaments are sufficient to drive ASC speck formation in cultured human cells—a process that is greatly enhanced by NLRP1-FIINDUPA which forms oligomers in vitro. The cryo-EM structures of NLRP1-CARD and CARD8-CARD filaments, solved here at 3.7 Å, uncover unique structural features that enable NLRP1 and CARD8 to discriminate between ASC and pro-caspase-1. In summary, our findings provide structural insight into the mechanisms of activation for human NLRP1 and CARD8 and reveal how highly specific signaling can be achieved by heterotypic CARD interactions within the inflammasome complexes., NLRP1 and CARD8 are two recently described sensor proteins for the human inflammasome complex. Here, the authors present the cryo-EM CARD filament structures of the NLRP1 and CARD8 activating domains, which reveal how NLRP1 and CARD8 discriminate between ASC and pro-caspase-1. They further propose a two-step model for NLRP1 activation.

SUMMARY2′,3′-cAMP is a positional isomer of the well-established second messenger 3′,5′-cAMP, but little is known on the biology of this noncanonical cyclic nucleotide monophosphate (cNMP). Toll/interleukin-1 receptor (TIR) domains of nucleotide-binding leucine-rich repeat (NLR) immune receptors have NADase function necessary but insufficient to activate plant immune responses. Here we show that plant TIR proteins, besides being NADases, act as 2′,3′-cAMP/cGMP synthetases by hydrolyzing RNA/DNA. Structural data shows that a TIR domain adopts distinct oligomers with dual and exclusive enzymatic activity. Mutations specifically disrupting the synthetase activity abrogate TIR-mediated cell death inNicotiana benthamiana, supporting an important role for these cNMPs in TIR signaling. Furthermore, theArabidopsisnegative regulator of TIR-NLR signaling, NUDT7 displays 2′,3′-cAMP/cGMP but not 3′,5′-cAMP/cGMP phosphodiesterase activity and suppresses cell death activity of TIRs inN. benthamiana. Our study identifies a novel family of 2′,3′-cAMP/cGMP synthetase and establishes a role for the noncanonical cNMPs in plant immune responses.

6D pose estimation of objects is essential for intelligent manufacturing. Current methods mainly place emphasis on the single object’s pose estimation, which limit its use in real-world applications. In this paper, we propose a multi-instance framework of 6D pose estimation for textureless objects in an industrial environment. We use a two-stage pipeline for this purpose. In the detection stage, EfficientDet is used to detect target instances from the image. In the pose estimation stage, the cropped images are first interpolated into a fixed size, then fed into a pseudo-siamese graph matching network to calculate dense point correspondences. A modified circle loss is defined to measure the differences of positive and negative correspondences. Experiments on the antenna support demonstrate the effectiveness and advantages of our proposed method.

High mobility group box 1 (HMGB1) is an alarmin that may link to obesity and type 2 diabetes mellitus (T2DM). The present study analyzed the correlation between HMGB1/ Toll-like receptor 4 (TLR4) and certain biochemical parameters in obese (OB) diabetic patients. 40 normal glucose tolerant subjects (NGT) and 40 patients with newly diagnosed T2DM were enrolled. All patients were further divided into non-obese NGT (NGT-NOB), obese NGT (NGT-OB), non-obese T2DM (T2DM-NOB) and obese T2DM (T2DM-OB) groups according to body mass index (BMI).The levels of HMGB1 in serum were quantified using ELISA, whereas the mRNA expression levels of TLR4 in peripheral blood mononuclear cells were assessed using reverse transcription-quantitative PCR. The results suggested that the levels of HMGB1 and TLR4 were higher in NGT-OB and T2DM-NOB groups compared with those in NGT-NOB group. Similarly, the levels of these two markers were higher in T2DM-OB group compared with those in NGT-OB group. Correlation analysis indicated that the levels of HMGB1 and TLR4 were positively correlated with triglyceride (TG), fasting plasma glucose (FPG) levels and BMI, whereas a negative correlation between HMGB1 and high density lipoprotein (HDL) was noted. Linear regression analysis suggested that HMGB1 was associated with FPG and TG levels, whereas TLR4 was strongly associated with TG levels and BMI. The results demonstrated that the expression levels of HMGB1 and TLR4 in patients with T2DM or obesity were increased, which were associated with glycolipid metabolism disorders. Therefore, the HMGB1/TLR4 may serve a role in inflammatory process associated with obesity and T2DM.

Herein, through the interfacial regulation of cucurbiturils (CBs) on Fe3O4-Au nanoparticles, a novel multifunctional platform is constructed for the sensitive detection of Cd2+ and the selective catalytic reduction (SCR) of nitrocompounds. The reported surface modification strategy provides an efficient approach to prepare a new platform for multiple purposes.

Composite oxide catalysts with Co/Mn/Ce molar ratio of 3:x:2(x = 1, 3, 5 and 7) have been successfully prepared by co-precipitation method. The crystal phase structure, elemental valence, oxygen vacancy and reductivity of the catalysts were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), H2 temperature program reduction(H2-TPR) and in situ DRIFTs. The results demonstrated that when x = 1, the Co–Mn–Ce catalyst had the smallest grain size and oxygen vacancy. A flow reactor experimental system was used to analyze the effect of Mn content on light-off temperature (T10) and complete oxidation temperature (T90) of propane oxidation over Co–Mn–Ce catalysts under anhydrous condition and 5% vol of water vapor. The results showed that when x = 1, the catalyst exhibits the highest activity (T10 = 200 °C, T90 = 307 °C) and water tolerance among the four catalysts. It indicated that when x = 1, the incorporation of Mn content can improve the ability of Co–Mn–Ce catalysts for propane oxidation. Based on the Langmuir–Hinshelwood theory, the surface chemical reaction pathway of propane oxidation was constructed and it revealed that the major active sites of Co–Mn–Ce catalysts mainly depend on surface oxygen vacancy and the surface active species (Mn4+,Oads).

Background Plant architecture, which is mostly determined by shoot branching, plays an important role in plant growth and development. Thus, it is essential to explore the regulatory molecular mechanism of branching patterns based on the economic and ecological importance. In our previous work, a multiple-branches birch mutant br was identified from 19 CINNAMOYL-COENZYME A REDUCTASE 1 (CCR1)-overexpressed transgenic lines, and the expression patterns of differentially expressed genes in br were analyzed. In this study, we further explored some other characteristics of br, including plant architecture, wood properties, photosynthetic characteristics, and IAA and Zeatin contents. Meanwhile, the T-DNA insertion sites caused by the insertion of exogenous BpCCR1 in br were identified to explain the causes of the mutation phenotypes. Results The mutant br exhibited slower growth, more abundant and weaker branches, and lower wood basic density and lignin content than BpCCR1 transgenic line (OE2) and wild type (WT). Compared to WT and OE2, br had high stomatal conductance (Gs), transpiration rate (Tr), but a low non-photochemical quenching coefficient (NPQ) and chlorophyll content. In addition, br displayed an equal IAA and Zeatin content ratio of main branches’ apical buds to lateral branches’ apical buds and high ratio of Zeatin to IAA content. Two T-DNA insertion sites caused by the insertion of exogenous BpCCR1 in br genome were found. On one site, chromosome 2 (Chr2), no known gene was detected on the flanking sequence. The other site was on Chr5, with an insertion of 388 bp T-DNA sequence, resulting in deletion of 107 bp 5′ untranslated region (UTR) and 264 bp coding sequence (CDS) on CORONATINE INSENSITIVE 1 (BpCOII). In comparison with OE2 and WT, BpCOI1 was down-regulated in br, and the sensitivity of br to Methyl Jasmonate (MeJA) was abnormal. Conclusions Plant architecture, wood properties, photosynthetic characteristics, and IAA and Zeatin contents in main and lateral branches’ apical buds changed in br over the study’s time period. One T-DNA insertion was identified on the first exon of BpCOI1, which resulted in the reduction of BpCOI1 expression and abnormal perception to MeJA in br. These mutation phenotypes might be associated with a partial loss of BpCOI1 in birch.

Piperine (PIP) demonstrates extensive pharmacological effects. Recent studies reported that PIP enhanced osteogenic differentiation and inhibited osteoclast functions. Nevertheless, its effect has not been evaluated in vivo. In the current study, ovariectomised female mice and MC3T3-E1 cells were used to examine its effect on osteoblastogenesis. Oral administration of PIP significantly elevated bone mineral density and suppressed bone remodeling without dose dependence. The deterioration of trabecula and biomechanical properties were significantly improved. Moreover, new bone formation was also accelerated with increased mineral apposition rate. At the presence of PIP, the cell proliferation and alkaline phosphatase as well as mineralized nodules formation were significantly enhanced. The expression of osteogenic markers and Wnt/β-catenin signals were significantly up-regulated by the treatment of PIP. Conclusively, as an alternative supplement or functional food ingredient, PIP has the potential to treat osteoporosis induced by estrogen deficiency by enhancing osteogenic differentiation via Wnt/β-catenin signaling.

A new strategy to effectively lock the conformation of substituents at the 3,3′-positions of axial-chiral biisoquinoline N,N’-dioxides was developed based on the strong dipole–dipole interaction between 1,2,3-triazole and pyridine N-oxide rings. The crystal structure and the DFT calculations of 3,3′-bis(1-benzyl-1H-1,2,3-triazole-4-yl)-1,1′-biisoquinoline N,N’-dioxide (3a) provided strong support for this strategy. Furthermore, we successfully demonstrated that readily available 4-trimethylsilyl-1,2,3-triazoles are viable nucleophiles for Hiyama cross-coupling.

Nuclear Thermal Propulsion (NTP) for deep space exploration is promising. Hydrogen is employed as the propellant to enhance the maximized specific impulse of NTP. Whereas, the low boiling point and density of hydrogen lead to several issues related to safety and storage. From the perspective of reactor physics, thermal hydraulics, material compatibility, and experience in the aerospace field, ammonia (NH3) is the alternative propellant to replace hydrogen. To analyze the specific impulse and system parameters of ammonia NTP, the hydrogen expander cycle NTP system analysis program PANES (Program for Analyzing Nuclear Engine Systems) is improved. The thermophysical properties library of ammonia has been increased in PANES. Based on the same thrust with hydrogen NTP, the design and analysis of ammonia NTP systems are carried out. This paper improves the PANES program and calculates the NTP performance parameters for potential alternative propellant ammonia, which provides a reference for the design of ammonia NTP system.

pH-sensitive hydrogels have been applied in delivering probiotics and drugs. However, pH sensitivity has been found to be contradictory with structural stability in hydrogel preparation. In this work, a novel strategy based on two systems of sodium carboxymethyl cellulose (CMC)/chitosan (CS) and sodium alginate (SA)/calcium chloride was designed to construct a reticulated shell structure stable for 3 h in simulated gastric fluid (pH 1.2) but began to break up at 2 h in simulated intestinal fluid (pH 6.8), exhibiting obvious pH sensitivity. The embedding rate of Bacillus subtilis natto reached to 67.3%, and the sustained release lasted for more than 10 h. It is implicated that the reticulated shell structure has harmoniously balanced the two incompatible properties of pH sensitivity and sustained release of CMC/CS/SA beads.

Background: The anti-tumor effect of IL-36β mediated activation of CD8+ T cells has been reported, but the molecular mechanism is largely undefined.Methods: IL-36β amounts in pancreatic cancer were examined by qRT-PCR and immunohistochemical staining. Cytology and animal experiments were performed to study the effects of IL-36β on the growth of pancreatic cancer cells. Then we examined the changes of CD8+ T cells and NK cells in the tumor flow-cytometrically. MicroRNA expression profiles were determined by microarray analysis.Results: The results revealed decreased IL-36β amounts in pancreatic cancer tissues. In addition, IL-36β inhibited tumor growth and promoted CD8+ T and NK cell proliferation in the tumor microenvironment. Moreover, IL-36β stimulated CD8+ T cells to synthesize high amounts of IFN-γ and IL-2. Microarray analysis showed that IL-36β administration to human and mouse CD8+ T cells consistently downregulated the miRNA let-7c-5p. Downregulation of let-7c-5p resulted in IFN-γ and IL-2 upregulation in CD8+ T Cells, whereas its upregulation had the opposite effects. Further experiments demonstrated that IL-36β downregulated IFN-γ in let-7c-5p+ CD8+ T cells. Conclusion: These findings suggest IL-36β promotes IFN-γ and IL-2 production in CD8+ T cells, and IL-36β promotes anti-tumor effects in CD8+ T cells by downregulating micro-RNA let-7c-5p.

The endoplasmic reticulum (ER) is one of the most important cellular organelles and is essential for cell homeostasis. Upon external stimulation, ER stress induces the unfolded protein response (UPR) and ER-associated degradation (ERAD) to maintain ER homeostasis. However, persistent ER stress can lead to cell damage. ER-phagy is a selective form of autophagy that ensures the timely removal of damaged ER, thereby protecting cells from damage caused by excessive ER stress. As ER-phagy is a newly identified form of autophagy, many receptor-mediated ER-phagy pathways have been discovered in recent years. In this review, we summarize our understanding of the maintenance of ER homeostasis and describe the receptors identified to date. Finally, the relationships between ER-phagy and diseases are also discussed.

In the clinical application of Traditional Chinese Medicine (TCM) substitutes, the consistency evaluation of TCM substitutes from different sources is recognized as the main bottleneck. As the most widely used analytical method in TCM consistency evaluation, fingerprint similarity evaluation suffers from insufficient method sensitivity and poor conformity with the actual characteristics of TCM, which is difficult to adapt to the analytical needs of complex substance systems of TCM. This work aims to develop an effective and more accurate method for consistency evaluation using omics strategy and machine learning algorithms. The natural calculus bovis (NCB) were graded into three groups according to the similarity to in vitro cultured bovis (IVCB), and chemical markers between samples of each grade were screened out. Support vector machine (SVM) models with different kernels were then constructed by using the chemical markers as feature variables. The results showed that the classification accuracy of the SVM classifier of NCB and the consistency evaluation SVM model classifier was 95.74% and 100.0%, respectively. The approach demonstrated in the study presented a good analytical performance with higher sensitivity, accuracy for consistency evaluation of TCM.

A nanozyme based on graphene oxide modified with Fe3O4 NPs, CuO NPs, and cucurbit[6]uril has been successfully fabricated by a simple sonochemical technique. By employing CB[6] as a specific binding pocket and Fe3O4@CuO-GO as a peroxidase mimic, this novel nanozyme (BN I) is equipped with molecular recognition ability and enhanced peroxidase-like activity. On the basis of the inhibition effect of homocysteine (Hcy) towards the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) catalyzed by BN I, a simple colorimetric method is established for the sensitive and selective determination of Hcy. This proposed method displays a good linear response in the range 5–200 μM with a detection limit of 1.8 μM. In the practical assay of human plasma samples, the relative standard deviations (RSD) are lower than 11% and the recoveries are between 98.0 and 104.9%. In the assay of human urine samples, the RSD are below 9.0% and the recoveries range from 94.0 to 103.5%. The colorimetric method presented offers a convenient and accurate way for the determination of biomarkers in point-of-care testing (POCT).

The efficient copper-mediated oxidative C–H alkynylaiton of benzhydrazides was accomplished with terminal alkynes. Thus, a hetero-aromatic removable N-2-pyridylhydrazide allowed for domino C–H/N–H functionalization. The approach featured remarkable functional group compatibility and ample substrates scope. Thereby, highly functionalized aromatic and hetero-aromatic isoindolin-1-ones were accessed with high efficacy with rate-limiting C–H cleavage.

Ectopic fat deposition (EFD) in the kidney plays a key role in the development of diabetic nephropathy (DN). Mitochondria-associated ER membranes (MAMs) are structures that connect to the endoplasmic reticulum (ER) and are involved in lipid metabolism. However, there are few studies on MAMs in the field of kidney disease, and the relationship between EFD and MAMs in DN is still unclear. In this study, increased EFD in the kidneys of DN patients was observed, and analysis showed that the degree of EFD was positively correlated with renal damage. Then, the MAMs were quantified by an in situ proximity ligation assay (PLA). The MAMs in the kidneys were found to gradually decrease through the different stages of DN, while the expression of ADRP (a marker of lipid droplets) and tubulointerstitial damage increased. Moreover, correlation analysis showed that the MAMs were negatively correlated with serum lipid levels, the EFD in the kidney and renal damage. Finally, we observed decreased expression of MAM-control proteins (DsbA-L, PACS-2, and MFN-2) in different stages of DN and they were associated with lipid deposition and renal damage. These data showed that the destruction of MAMs in DN might be the cause of EFD and interstitial damage in the kidney.

PP2C protein phosphatase family is one of the largest gene families in the plant genome. Many PP2C family members are involved in the regulation of abiotic stress. We found that BpPP2C1 gene has highly up-regulated in root under salt stress in Betula platyphylla. Thus, transgenic plants of Betula platyphylla with overexpression and knockout of BpPP2C1 gene were generated using a zygote transformation system. Under NaCl stress treatment, we measured the phenotypic traits of transgenic plants, chlorophyll-fluorescence parameters, peroxidase (POD) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content. We found that BpPP2C1 overexpressed lines showed obvious salt tolerance, while BpPP2C1 knocked out plants were sensitive to salt stress. Transcriptome analysis identified significantly amount of differentially expressed genes associated with salt stress in BpPP2C1 transgenic lines, especially genes in abscisic acid signaling pathway, flavonoid biosynthetic pathway, oxidative stress and anion transport. Functional study of BpPP2C1 in Betula platyphylla revealed its role in salt stress.

Assembly of extracellular filaments and matrices mediating fundamental biological processes such as morphogenesis, hearing, fertilization, and antibacterial defense is driven by a ubiquitous polymerization module known as zona pellucida (ZP) “domain”. Despite the conservation of this element from hydra to humans, no detailed information is available on the filamentous conformation of any ZP module protein. Here, we report a cryo‐electron microscopy study of uromodulin (UMOD)/Tamm–Horsfall protein, the most abundant protein in human urine and an archetypal ZP module‐containing molecule, in its mature homopolymeric state. UMOD forms a one‐start helix with an unprecedented 180‐degree twist between subunits enfolded by interdomain linkers that have completely reorganized as a result of propeptide dissociation. Lateral interaction between filaments in the urine generates sheets exposing a checkerboard of binding sites to capture uropathogenic bacteria, and UMOD‐based models of heteromeric vertebrate egg coat filaments identify a common sperm‐binding region at the interface between subunits., Insights into the architecture of uromodulin filaments involved in the capture of uropathogenic bacteria, and structurally‐related vertebrate egg coat material, suggest how a widespread extracellular polymerization module can support multiple functions.

Autophagy is a process of intracellular self-recycling and degradation that plays an important role in maintaining cell homeostasis. However, the molecular mechanism of autophagy remains to be further studied. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are the region of the ER that mediate communication between the ER and mitochondria. MAMs have been demonstrated to be involved in autophagy, Ca2+ transport and lipid metabolism. Here, we discuss the composition and function of MAMs, more specifically, to emphasize the role of MAMs in regulating autophagy. Finally, some key information that may be useful for future research is summarized.

Nod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling and activating the inflammasome complex. Closely related NLR proteins, NLRP1 and CARD8 undergo unique auto-proteolysis-dependent activation and are implicated in auto-inflammatory diseases; however, the molecular mechanisms of activation are not understood. Here we report the structural basis of how the activating domains (FIINDUPA-CARD) of NLRP1 and CARD8 self-oligomerize to trigger the assembly of distinct inflammasome complexes. Recombinant FIINDUPA-CARD of NLRP1 forms a two-layered filament, with an inner core composed of oligomerized CARD domains and the outer layer consisting of FIINDUPA rings. Biochemically, oligomerized NLRP1-CARD is sufficient to drive ASC speck formation in cultured human cells via filament formation-a process that is greatly enhanced by NLRP1-FIINDUPA, which forms ring-like oligomers in vitro. In addition, we report the cryo-EM structures of NLRP1-CARD and CARD8-CARD filaments at 3.7 Å, which uncovers unique structural features that enable NLRP1 and CARD8 to discriminate between ASC and pro-caspase-1. In summary, our findings provide unique structural insight into the mechanisms of activation for human NLRP1 and CARD8, uncovering an unexpected level of specificity in inflammasome signaling mediated by heterotypic CARD domain interactions.

SUMMARYAssembly of extracellular filaments and matrices mediating fundamental biological processes such as morphogenesis, hearing, fertilization and antibacterial defense is driven by a ubiquitous polymerization module known as zona pellucida (ZP) “domain”. Despite the conservation of this element from hydra to human, no information is available on the filamentous conformation of any ZP module protein. Here we report the cryo-electron microscopy structure of uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant protein in human urine and an archetypal ZP module-containing molecule, in its mature homopolymeric state. UMOD forms a one-start helix with an unprecedented 180-degree twist between subunits enfolded by interdomain linkers that have completely reorganized as a result of propeptide dissociation. Lateral interaction between filaments in the urine generates sheets exposing a checkerboard of binding sites to capture uropathogenic bacteria, and UMOD-based models of mammalian and avian heteromeric egg coat filaments identify a common sperm-binding region at the interface between subunits.

Recent studies demonstrate that diet quercetin (Quer) has obvious bone protective effects on ovariectomized rodents but thus far there is no direct evidence to support the inhibitory effect of Quer on bone loss caused by long-term unloading. In the present study, we investigated whether Quer could prevent bone loss induced by unloading in mice. Mice were subjected to hindlimb suspension (HLS) and received Quer (25, 50, 100 mg· kg(−1) ·day(−1), ig) for 4 weeks. Before euthanasia blood sample was collected; the femurs were harvested and subjected to MicroCT analysis. We showed that Quer administration markedly improved bone microstructure evidenced by dose-dependently reversing the reduction in bone volume per tissue volume, trabecular number, and bone mineral density, and the increase of trabecular spacing in mice with HLS. Analysis of serum markers and bone histometric parameters confirmed that Quer at both middle and high doses significantly decreased bone resorption-related markers collagen type I and tartrate-resistant acid phosphatase 5b, and increased bone formation-related marker procollagen 1 N-terminal propeptide as compared with HLS group. Treatment with Quer (1, 2, 5 μM) dose-dependently inhibited RANKL-induced osteoclastogenesis through promoting the expression of antioxidant hormone stanniocalcin 1 (STC1) and decreasing ROS generation; knockdown of STC1 blocked the inhibitory effect of Quer on ROS generation. Knockdown of STC1 also significantly promoted osteoclastogenesis in primary osteoclasts. In conclusion, Quer protects bones and prevents unloading-caused bone loss in mice through STC1-mediated inhibition of osteoclastogenesis. The findings suggest that Quer has the potential to prevent and treat off-load bone loss as an alternative supplement.

Multi interfaces Al-TiAlN nanocomposite films were deposited on AZ91D magnesium alloy with ion source hybrid magnetron sputtering. Relationship between microstructure evolution and corrosion resistance of the films was investigated. The results show that the column structure is interrupted by multi interfaces. The nanocomposite films are consisted of nanocrystal TiN and amorphous AlN phase. The highest hardness of 31.3 GPa and lowest corrosion current density of 9.37 × 10−8 A/cm2 can be obtained by tuning the interface period. The deflection effect of multi interfaces is the key for the improved corrosion resistance, and the failure mechanism is related to pitting and filiform corrosion.

A novel porous ferrosilicon nitride (Fe3Si–Si3N4) ceramic sliding gate was prepared and applied in a ladle in a steel mill; it was characterised by X-ray diffraction analysis, scanning electron microscopy, and energy-dispersive spectroscopy. The results showed that after use, the sliding gate consisted of a reaction layer (0–1.5 mm), a transition layer (1.5–2.2 mm), a gradient layer (2.2–20 mm), and an unaltered layer. In the reaction layer, Si3N4 is decomposed, and the structure is damaged; in the transition layer, Si3N4 is stable, and the structure shows no obvious change; in the gradient layer, Si3N4 is oxidised slightly. The reaction mechanism is as follows. The structure of the original porous ferrosilicon nitride resembles a sea urchin, and β-Si3N4 columns are bundled together by Fe3Si. During operation, Fe3Si reacts with molten steel to form an Fe/FeSi melt, which attacks the structure, whereas Si3N4 decomposes to the product N2(g) [ Si 3 N 4 ( s ) + F e ( l ) → FeSi ( l ) + N 2 ( g ) ]. N2(g) forms a high-pressure gas cushion that blocks the molten steel, protecting the inner part of the sliding gate, so Si3N4 remains stable in the transition layer. Further inward, Si3N4 is oxidised slightly by trace [O] from the molten steel to generate silicon oxynitride. The reaction model was established.

In order to prepare a synergetic flame retardant, the magnesium hydroxide (MH) and hexaphenoxycyclotriphosphazene (HPCTP) were blended with ethylene–vinyl acetate copolymer (EVA). The EVA–MH–HPCTP composite materials were characterized by various tests including Fourier transform infrared spectroscopy, X-ray diffractometer and scanning electron microscopy (SEM). The SEM images indicated that the compatibility of EVA–MH–HPCTP composite materials was significantly promoted due to the bridging effect of HPCTP. Therefore, the EVA–MH–HPCTP composite materials possessed better processability which was evidenced by the melt flow rate tests. Comparing to the traditional addition dosage (over 50%) of MH in previous reports, the EVA–MH–HPCTP composite materials showed significant flame-retardant efficiency even when the dosage of MH was lowered to 20 parts per hundred resins. The experimental results suggest that the prepared EVA–MH–HPCTP composite material may be a potential candidate in various industrial applications due to its excellent flame retardant.