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Background Osteoarthritis (OA) represents a significant disabling condition that has been well documented as a significant health burden. Lymphocyte-specific kinase (LCK) has been reported to exhibit differential expression in OA. However, the specific mechanism of LCK in OA remains relatively unknown. Herein, the current study aimed to elucidate the role of LCK in cartilage injury in OA in relation to the nuclear factor-kappa B (NF-κB) pathway. Methods The expression of LCK was determined in the collected cartilage tissues of patients with OA as well as the OA rat models. Gain- and loss-of-function approaches were conducted on the OA rat model as well as the interleukin-1β (IL-1β)-induced in vitro OA model to further explore the role of LCK in chondrocyte proliferation and apoptosis, extracellular matrix (ECM) degradation and inflammation. Results LCK was highly expressed in the cartilage tissues of both patients and rats with OA. LCK silencing led to a reduction in the rate of apoptosis, inflammation, and degree of ECM degradation in the cartilage tissues of OA rats. In the IL-1β-induced chondrocytes, LCK silencing repressed apoptosis, inflammation and ECM degradation, while acting to elevate viability. LCK silencing inhibited activation of NF-κB in OA. LCK was found to activate the NF-κB pathway which heightened apoptosis, inflammation and ECM degradation while lowering viability in the IL-1β-induced chondrocytes. Conclusion Taken together, our study demonstrates that silencing of LCK promotes cartilage repair in OA by inhibiting the NF-κB pathway and diminishing IL-1β-induced chondrocyte inflammation as well as ECM degradation.

Despite numerous efforts to treat wastewater with sulfonamides, their mineralization has rarely been achieved, resulting in the generation of more toxic by-products. In this study, greater than 75% mineralization of sulfamerazine (SMR) was achieved following 4 h of electrochemical oxidation. Remarkably, the Microtox® toxicity test confirmed the elimination of by-products with higher toxicity. The electrochemical treatment process was carried out using a dynamic oxygen-vacancy-mediated TiO2 anode (TiO2-OV@Ti-F), which comprised oxygen-deficient Ti4O7 coated on titanium-foam (Ti-F) via thermal spraying, allowing simultaneous high reactivity and mass transfer. SMR degradation followed a pseudo-first-order kinetics model, where the rate constant (kapp = 1.64 × 10−2 min−1) for the rotary TiO2-OV@Ti-F configuration was 1.98-fold greater than that of the static one (kapp = 8.30 × 10−3 min−1). This highlights the superiority of the rotary TiO2-OV@Ti-F anode for SMR decay. The high oxidation capabilities arose from: (i) the synergetic effect between the rotating system and the Ti4O7 coating; (ii) the enhanced mass transfer coefficient (3.49 × 10−5 m s−1) in the rotating configuration, as well as the increase in SMR degradation via direct oxidation, due to a low hole injection energy, as supported by density functional theory calculations; and (iii) boosted ˙OH formation achieved via removing the gas bubbles attached to the anode, along with lower adsorption energies for H2O and ˙OH. The results revealed that rotary TiO2-OV@Ti-F is a promising alternative for antibiotic wastewater treatment owing to its high organic mineralization and low level of energy consumption (0.29 kW per h per gTOC).

Hypothesis Understanding the effect of cations on membrane fouling is crucial for the widespread application of the membrane technology. However, contradictory results have been reported based on different studies. Moreover, although the effect of the ionic strength has been studied extensively, limited information is available on the effect of the ion type on membrane fouling. Experiments The physicochemical properties of the membrane and anionic polyacrylamide (APAM) were evaluated to calculate the APAM–membrane and APAM–APAM interfacial interaction energies under different conditions. Moreover, a series of microfiltration (MF) experiments was conducted to investigate the effects of the ionic conditions on the flux decline, pore blockage and cake layer resistances, and the flux recovery rate of APAM during the MF process. Findings As the ionic strength increased, the rate of decrease in the normalized flux increased, the total and cake layer resistances increased significantly, the pore blockage resistance was affected slightly, and the recovery rates of the water flux after physical and chemical cleaning decreased gradually, which could be clearly explained using the Derjaguin–Landau–Verwey–Overbeek theory. Furthermore, compared with Na+, Ca2+ could effectively mitigate the membrane fouling at an identical ionic strength, which is attributed to the hydration forces of APAM–membrane and APAM–APAM.

As global warming has become a major environmental problem, how to effectively reduce or rationally utilize greenhouse gases has become an important topic. This review summarizes the latest development of Ni-based catalysts for thermal-catalytic conversion of CO2 and CH4, including steam reforming of methane, partial oxidation of methane, methane decomposition, dry reforming of methane, reverse water gas shift reaction and CO2 hydrogenation. The modification strategies are illustrated in depth, such as size and dispersion control, surface modification, oxygen defects. Besides, the reaction and coking mechanisms for various processes are introduced, and the effects of reaction conditions and reactor designs are discussed and illustrated. This is the first comprehensive review on discussing the latest developments of anti-coking Ni-based catalysts for six commonly studied thermal-catalytic processes where two greenhouse gases (CH4 and CO2) are involved. To further improve the catalytic performances and energy efficiency, advanced techniques such as plasma and microwave can be integrated and in-situ characterizations are expected to explore the deactivation mechanisms in depth. Moreover, a smart design of the catalyst is necessary to inhibit the side reactions by changing the reaction pathways.

Recombinant tissue-type plasminogen activator (rtPA) is the clot lysis drug approved for clinical use, and is characterised by a short half-life and substantial inactivation by plasminogen activator inhibitor-1 (PAI-1). We previously discovered that a tPA mutation (A419Y) at the protease domain led to enhanced fibrinolysis activity. In the present study, we studied the mechanism of such mutation in enhancing the proteolytic activity, and whether such enhancement persists in reteplase, an United States Food and Drug Administration-approved tPA truncated variant. We constructed and expressed a series of reteplase-based mutants, including rPAG (glycosylated rPA), rPAG -Y (with A419Y mutant at rPAG ), rPAG -A4 (tetra-alanine mutation at 37-loop of rPAG ), and rPAG -A4/Y (with both) and evaluated their plasminogen activation and PAI-1 resistance. Surface plasmon resonance analysis showed that the rPAG had fibrin affinity comparable to full-length tPA. Moreover, rPAG -Y had 8·5-fold higher plasminogen activation and stronger tolerance to PAI-1 compared to rPAG . We also found that the mutations containing tetra-alanine (rPAG -A4 and rPAG -A4/Y) had dramatically reduced plasminogen activation and impaired clot lysis. In a pulmonary embolism murine model, rPAG -Y displayed a more efficient thrombolytic effect than rPAG . These results identified a novel mutant reteplase variant of tPA with increased fibrinolytic activity, laying the foundation for the development of a new potent fibrinolytic agent.

As a new carbon allotrope, graphdiyne(GDY) has shown intensive practical application prospects in the energy field, catalysis, gas separation, etc., due to its unique 2D π-conjugated structure, rich sp-hybridized carbon atoms and semiconductor characteristics. Considerable efforts have been made to the development of well-defined GDY materials in recent years. The doping heteroatoms can further tune the structures, semiconductor properties of GDY, and expand the promising applications. This review summarized a comprehensive development of heteroatom doped GDYs, including their synthesis, structures, properties, applications in nanotechnology, as well as the forecast in the future.

A new generation of bioplatform molecule 5-ethoxymethylfurfural (EMF) has excellent energy density and combustion performance, which makes it a potential fuel additive. This article reviews the factors that affect the production of EMF from different feedstocks, including platform compounds, monosaccharides, polysaccharides, and raw lignocellulosic biomass. Focus is placed on discussing the catalytic efficiency with pros and cons of different acid catalysts, including homogeneous catalysts (i.e., liquid acids and metal salts), heterogeneous catalysts (i.e., zeolites, heteropolyacid-based hybrids, and SO3H-based catalysts), ionic liquids, mixed acid catalysts, and deep eutectic solvents (DESs). Except for the commonly used ethanol solvent, this review also summarizes the influence of the cosolvent system (e.g., ethanol/dimethylsulfoxide (DMSO), ethanol/tetrahydrofuran (THF), and ethanol/γ-valerolactone (GVL)) on the EMF yield.

Background Uncontrollable inflammation and nerve cell apoptosis are the most destructive pathological response after spinal cord injury (SCI). So, inflammation suppression combined with neuroprotection is one of the most promising strategies to treat SCI. Engineered extracellular vesicles with anti-inflammatory and neuroprotective properties are promising candidates for implementing these strategies for the treatment of SCI. Results By combining nerve growth factor (NGF) and curcumin (Cur), we prepared stable engineered extracellular vesicles of approximately 120 nm from primary M2 macrophages with anti-inflammatory and neuroprotective properties (Cur@EVs−cl−NGF). Notably, NGF was coupled with EVs by matrix metalloproteinase 9 (MMP9)-a cleavable linker to release at the injured site accurately. Through targeted experiments, we found that these extracellular vesicles could actively and effectively accumulate at the injured site of SCI mice, which greatly improved the bioavailability of the drugs. Subsequently, Cur@EVs−cl−NGF reached the injured site and could effectively inhibit the uncontrollable inflammatory response to protect the spinal cord from secondary damage; in addition, Cur@EVs−cl−NGF could release NGF into the microenvironment in time to exert a neuroprotective effect against nerve cell damage. Conclusions A series of in vivo and in vitro experiments showed that the engineered extracellular vesicles significantly improved the microenvironment after injury and promoted the recovery of motor function after SCI. We provide a new method for inflammation suppression combined with neuroprotective strategies to treat SCI. Graphical Abstract

Specific and sensitive detection of nucleic acids is essential to clinical diagnostics and biotechnological applications. Currently, amplification steps are necessary for most detection methods due to the low concentration of nucleic acid targets in real samples. Although amplification renders high sensitivity, poor specificity is prevalent because of the lack of highly accurate precise strategies, resulting in significant false positives and false negatives. Nucleases exhibit high catalytic activity for nucleic acid cleavage which is regulated in a programmable manner. This review focuses on the latest progress in nucleic acid testing methods based on the target-activated nucleases. It summarizes the property of enzymes such as CRISPR/Cas, Argonautes, and some gene-editing irrelevant nucleases, which have been leveraged to create highly specific and sensitive nucleic acid testing tools. We elaborate on recent advances in the field of nuclease-mediated DNA recognition techniques for nucleic acid detection, and discuss its future applications and challenges in molecular diagnostics.

Objective: The aim of this study was to screen for compounds with relatively high inhibitory activity on acetylcholinesterase. Methods: Classification models for acetylcholinesterase inhibitors based on KNN (1-nearest neighbors), and a quantitative prediction model based on support vector machine regression were used. The interaction of the compounds and receptors was analyzed using the molecular simulation method. Results: The radial basis kernel function was selected as the kernel function for support vector machine regression, and a total of 19 descriptors were selected to construct the quantitative prediction model.

A novel 9,9a-BN anthracene 5 has been synthesized by the Ru-catalyzed electrocyclization of BN-aromatic enynes. The photophysical properties of 5 are different from those of all-carbon anthracene and other reported BN-anthracenes. The reactivity of 5 has been investigated by treating 5 with organolithium compounds, Br2, or N-iodosuccinimide. The resulting halogenated compounds can be easily functionalized via cross-coupling reactions. UV-vis and fluorescence spectroscopy of 5 have been investigated to explore the photophysical properties of these BN-anthracenes.

Laparoscopic anatomic mesohepatectomy for patients with hepatocellular carcinoma (HCC) remains technically challenging, especially for those with a massive tumor larger than 10 cm. In this study, a 65-year-old man with a 13 × 10-cm2 solitary liver tumor located at segments 4, 5, and 8 underwent laparoscopic mesohepatectomy. To reduce the possibility of releasing cancer cells from the primary tumor, the in situ resection strategy for tumor removal was implemented. The intrafascial approach was used to dissect the right Glissonean pedicle, to transect the right anterior hepatic artery, and to ligate the right anterior portal vein. The extrafascial and transfissural approach was performed along the umbilical fissure to transect the Glissonean pedicle of segment 4. Indocyanine green (ICG) then was applied using “reverse staining” to visualize the resection extent and the right posterior hepatic duct (RPHD). During parenchymal resection, the right anterior Glissonean pedicle was adequately exposed and transected via the extrafascial approach above the plane of the RPHD. Finally, the right coronary ligament was dissected, and the tumor was removed. The operation was completed in 360 min, with a blood loss of 200 mL. The histopathologic diagnosis indicated a moderately differentiated HCC. The patient was discharged on postoperative day 8 without any complications. Laparoscopic in situ anatomic mesohepatectomy using combined intra- and extrafascial approaches with ICG navigation may be feasible for patients with a centrally located solitary massive HCC.

LncRNA PROX1 antisense RNA 1 (PROX1-AS1) has been demonstrated to be upregulated in several kinds of cancers and serves as an oncogene. However, its role in the development of endometrial cancer (EC) remains unknown. The objective of this paper was to study the expression pattern of PROX1-AS1 in EC, and to reveal PROX1-AS1 role in EC progression, as well as the underlying mechanism. Bioinformatics method was applied to predict the binding sites between the transcription factor E2F1 and PROX1-AS1 promoter, and miR-424-5p and PROX1-AS1/CPEB2, and the targeting relationships were further verified by luciferase gene reporter assay, chromatin immunoprecipitation (ChIP) and RNA immunoprecipitation (RIP). The expression levels of E2F1 and PROX1-AS1 in cells were detected using qPCR and/or western blotting. The CCK-8 and colony formation assays were applied to determine cell growth and colony formation abilities. The results showed that PROX1-AS1 and E2F1 were highly expressed in EC cells. E2F1 promoted PROX1-AS1 expression via binding to the E1 part of PROX1-AS1 promoter, resulting in enhancements in cell growth and colony formation abilities. In addition, PROX1-AS1 targeted miR-424-5p and decreased miR-424-5p expression, which then induced a significant increase in CPEB2 expression. In conclusion, this study uncovered that PROX1-AS1 induced by E2F1 promoted the cell viability in EC through increasing CPEB2 expression via targeting miR-424-5p.

Summary China, the largest global CO2 emitter, recently announced ambitious targets for carbon neutrality by 2060. Its technical and economic feasibility is unclear given severe renewable integration barriers. Here, we developed a cross-sector, high-resolution assessment model to quantify optimal energy structures on provincial bases for different years. Hourly power system simulations for all provinces for a full year are incorporated on the basis of comprehensive grid data to quantify the renewable balancing costs. Results indicate that the conventional strategy of employing local wind, solar, and storage to realize 80% renewable penetration by 2050 would incur a formidable decarbonization cost of $27/ton despite lower levelized costs for renewables. Coordinated deployment of renewables, ultra-high-voltage transmissions, storages, Power-to-gas and slow-charging electric vehicles can reduce this carbon abatement cost to as low as $−25/ton. Were remaining emissions removed by carbon capture and sequestration technologies, achieving carbon neutrality could be not only feasible but also cost-competitive post 2050.

Methyl jasmonate (MeJA) is a plant growth regulator, which plays an important role in signaling defense response and regulating plant secondary metabolism. Here, broccoli hairy roots growing for 18 d were treated with MeJA for 0, 3, 6, 9, and 12 h, respectively. Compared with the 0 h control group, the content of glucoraphanin (GRA) and sulforaphane (SF) was increased under MeJA treatment for 3, 6, 9, and 12 h. The activity of myrosinase (MYR) was reduced in broccoli hairy roots. With the broccoli (Brassica oleracea L. var. botrytis L) genome as the reference genome, 4733 DEGs (differentially expressed genes) were detected in the hairy roots that were treated by MeJA for 0, 3, 6, 9, and 12 h; among them, 1024 genes were upregulated and 3709 genes were downregulated. The pathway of “SNARE interaction in vesicular transport” (ko04130) was ranked 1st by KEGG pathway enrichment analysis of commonly upregulated differential genes at 0, 3, 6, 9, and 12 h. The expression of four key genes ABCB19, ABCG6, ABCG36, and ABCB9, which regulated the release of GRA and SF into a liquid medium, was upregulated at 0, 3, 6, and 9 h, respectively. It revealed that the release of GRA and SF from hairy roots was related to the ABC transporter gene family and SNARE protein-mediated exocytosis by transcriptome analysis.

Previous studies have shown that melatonin (MT) can ameliorate vitrification-inflicted damage in mouse germinal vesicle (GV) oocytes, however, the key mechanistic basis of this improvement still remains poorly understood. This study was conducted to investigate whether MT can improve in vitro developmental potential of vitrified-warmed GV oocytes through its receptors. The fresh oocytes were randomly divided into four groups: untreated (control group, F), vitrified by open-pulled straw method (vitrification group, V), vitrification group with 100 nmol/L MT supplementation (vitrification + MT group, VM), and with 100 nmol/L MT plus 100 nmol/L luzindole administration (vitrification + MT + luzindole group, VML) or with 50 nmol/L ramelteon addition (vitrification + ramelteon group; VR). After warming, oocytes were cultured in vitro, and MT receptors (MTRs), MAD2 (mitotic arrest deficient 2), Securin and CyclinB1 protein levels and spindle morphology were evaluated. The ratio of oocytes developed to the metaphase I (MI) and metaphase II (MII) stages was also assessed. The results showed that after vitrification-warming, the in vitro maturation rate of GV oocytes was significantly lower compared to the control (F) group. Vitrification also significantly impaired the spindle morphology, decreased the protein level of MTRs and Securin, and decreased MAD2 levels in MI oocytes. However, when MT or ramelteon (MTRs agonist) were added (group wise) to warming and maturation media, the maturation rate of GV oocytes was significantly increased, the normal proportion of the spindle morphology increased, and the expression level of MAD2 increased in their resulting MI oocytes compared to the vitrification group. However, following addition of both MT and ramelteon, the maturation rate of GV oocyte showed no significant difference between VML and vitrification groups. The spindle morphology and MAD2 levels in MI oocytes were comparable to the vitrification group but differed significantly from the VM group. Taken together, finding of the present study shows that MT (100 nmol/L) can ameliorate the in vitro maturation of vitrified-warmed mouse GV oocytes, potentially by improving the spindle morphology, modulating MAD2 protein level and promoting the development of MI stage oocytes through MTRs.

A polysaccharide was obtained through the coculture of Ganoderma lucidum and Flammulina velutipes mycelia in submerged fermentation. Compared to G. lucidum monoculture, the coculture decreased cell biomass production and increased the exopolysaccharides (EPS) yield. In addition, the coculture EPS presented comparable antioxidant activity, however, enhanced anti-inflammatory activity. Under normal cultivation conditions, the coculture EPS displayed greater than 95 % cell viability to the hTERT-immortalized foreskin fibroblast cells. After UV irradiation, the coculture EPS presented less cytotoxicity than G. lucidum EPS when EPS concentration was 1.5 and 3.0 mg/mL. After serum starvation, the difference in the viability of the fibroblast cells treated by monoculture and coculture EPS was insignificant. Fractionation of the coculture EPS yielded one major fraction with a molecular weight of 1374.6 kDa. FT-IR analysis suggested that there existed both β-glucose and α-galactose in the coculture EPS, yet higher amount of β-glucose.

Purpose To evaluate whether ferroptosis is involved in hyperoxic acute lung injury (HALI) and its mechanisms through the HALI model. Methods HE staining was used to assess lung injury pathology after the establishment of neonatal rat HALI model. ELISA was used to detect ROS, GPX4, and GSH expression. Prussian blue staining and Western Blot were used to detect iron deposition and the expression of ferroptosis-related proteins, respectively. Results The HALI group showed pathological changes with larger and fewer alveoli and thicker alveolar septa after HE staining. Prussian blue staining detected significant iron deposition in the lung tissue of the HALI group. GPX4, GSH, GSS, and SLC7A11 expressions were significantly decreased in the HALI group than in the normal control group. In contrast, ROS, TFRC, FHC, and FLC expressions showed opposite results (p

Background Bladder cancer (BCa) is a common genitourinary malignancy with higher incidence in males. Long intergenic non-protein coding RNA 265 (LINC00265) is identified as an oncogene in many malignancies, while its role in BCa development remains unknown. Purpose To explore the functions and mechanism of LINC00265 in BCa Research Design Reverse transcription quantitative polymerase chain reaction was performed to examine LINC00265 expression in BCa cells. Cell counting kit-8 assays, colony formation assays, TdT-mediated dUTP Nick-End Labeling assays, and Transwell assays were conducted to examine BCa cell viability, proliferation, apoptosis, and migration. Luciferase reporter assays and RNA immunoprecipitation assays were carried out to explore the binding capacity between miR-4677-3p and messenger RNA fibroblast growth factor 6 (FGF6) (or LINC00265). Xenograft tumor model was established to explore the role of LINC00265 in vivo. Results LINC00265 was highly expressed in BCa cells. LINC00265 knockdown inhibited xenograft tumor growth and BCa cell viability, proliferation and migration while enhancing cell apoptosis. Moreover, LINC00265 interacted with miR-4677-3p to upregulate the expression of FGF6. FGF6 overexpression reversed the suppressive effect of LINC00265 knockdown on malignant phenotypes of BCa cells. Conclusions LINC00265 promotes the viability, proliferation, and migration of BCa cells by binding with miR-4677-3p to upregulate FGF6 expression.

The rhizosphere microbiome plays an important role in plant growth and behavior during phytoremediation. This work aims to explore how hyperaccumulating plant performance (shoot biomass and Cd uptake) and rhizosphere bacterial community are driven by plant development under a Cd concentration gradient and their relationship during plant growth. A pot experiment was conducted using the Cd hyperaccumulator Sedum plumbizincicola grown in soil spiked with 0, 5 and 20 mg Cd kg−1 for 13 weeks. Plant performance (shoot biomass and Cd uptake) was determined and the rhizosphere bacterial community was examined by weekly Illumina sequencing. Biomarker genera were identified by the Random Forest model and the functions were predicted by PICRUSt2. The rhizospheres bacterial community tended to stabilize from the 6th or 7th week regardless of the soil Cd concentration, coinciding with the vigorous growth stage of the hyperaccumulator. Biomarker genera Paenibacillus and Streptacidiphilus enriched in the stable stage showed significant positive correlations with Cd uptake. In addition, some predicted gene abundances of enzymes related to plant growth promotion by the rhizosphere bacterial community were influenced to various degrees by plant development and soil Cd concentration. There exists a stable bacterial community in the rhizosphere of S. plumbizincicola during phytoremediation and biomarker taxa enriched at this stage were positively correlated with Cd uptake. Selecting microorganisms that match the developmental stages might further enhance phytoremediation. This provides some theoretical basis for modulating rhizosphere microbes at the appropriate time during phytoextraction to optimize the phytoremediation technique.

Vulgarisins are members of diterpenoids with rare 5/6/4/5 ring skeleton from Prunella vulgaris Linn. (P. vulgaris). Their molecular scaffolds comprise different hydroxylation and degree of esterification. Vulgarisins have attracted many attentions in the fields of food and medicine for their potent bioactivities. Firstly, four reference compounds were analyzed by higher-energy collisional dissociation mass spectrometry (HCD MS/MS) and the fragmentation patterns for molecular scaffold were summarized. And then, a high-performance liquid chromatography/electrospray ionization/high-resolution mass spectrometry (HPLC-ESI-HR-MS) method was adopted to investigate the P. vulgaris extracts. Finally, the proposed analysis results were successfully applied to facilitate the discovery of the vulgarisins analogues from P. vulgaris. For the four reference compounds, the sodium adduct was the predominate ion in full scan. A specific fragmentation pathway of [M+Na]+ ions leads to produce diagnostic ions of vulgarisins at m/z 325 under HCD, which was formed through consecutive-side chains lost. Twenty-three diterpenoids, including 18 vulgarisins analogues, were identified or tentatively characterized in the botanical extracts of P. vulgaris based on their elemental constituents and characteristic fragment ion profiles. Two new vulgarisins analogues in the plant were isolated and their structures were illustrated based on extensive spectroscopic analysis using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. The HCD MS/MS method, including the profiles of the diagnostic ions induced by characteristic fragmentation, is an effective technique for the discovery of vulgarisins analogues in P. vulgaris. The expected fragmentation pattern knowledge will also facilitate the analysis of other natural products.

Tuning the facet exposure of Cu could promote the multi-carbon (C2+) products formation in electrocatalytic CO2 reduction. Here we report the design and realization of a dynamic deposition-etch-bombardment method for Cu(100) facets control without using capping agents and polymer binders. The synthesized Cu(100)-rich films lead to a high Faradaic efficiency of 86.5% and a full-cell electricity conversion efficiency of 36.5% towards C2+ products in a flow cell. By further scaling up the electrode into a 25 cm2 membrane electrode assembly system, the overall current can ramp up to 12 A while achieving a single-pass yield of 13.2% for C2+ products. An insight into the influence of Cu facets exposure on intermediates is provided by in situ spectroscopic methods supported by theoretical calculations. The collected information will enable the precise design of CO2 reduction reactions to obtain desired products, a step towards future industrial CO2 refineries. Regulation of Cu facets to promote electrocatalytic CO2 reduction is interesting and challenging. Here the authors describe a deposition-etch-bombardment synthetic approach to prepare Cu(100)-rich thin film electrodes for CO2 electroreduction with over 50% ethylene Faradaic efficiency at a total current of 12 A.

The development of low-price and highly efficient catalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) has always been challenging with regard to water splitting. Pyrrhotite Fe7S8 has become a research hotspot due to its abundant reserves, high electrical conductivity and excellent catalytic activity. In general, introducing metal heteroatoms into transition metal sulfides (TMSs) can effectively enhance the activity and stability of TMSs. Herein, Co-doped pyrrhotite Fe7S8 nanosheets were obtained by a straightforward two-step method consisting of hydrothermal treatment followed by subsequent heat treatment. Results from XPS analysis and contact angle measurements showed that doping optimized the chemical environment around iron atoms and enhanced the adsorption of water molecules on the surface of Fe7S8, thereby greatly improving the electrocatalytic efficiency of water electrolysis. Compared with other counterparts, Co0·95Fe6·05S8 exhibited superior OER activity with an overpotential of 311 mV at a current density of 10 mA cm−2, and higher performance towards HER with an overpotential of 284 mV at 10 mA cm−2 in alkaline solution. In sum, Co0·95Fe6·05S8 is promising as a bifunctional catalyst for water splitting under alkaline conditions.

Current electrospun membranes used for pulp capping still lack the sustained-release capability and long-term anti-inflammatory effects that are favorable for dental pulp regeneration. In this work, a single-layered poly(lactic acid) (PLA) electrospun membrane loaded with amorphous calcium phosphate (ACP) and aspirin (PLA/ACP/Aspirin membrane, i.e., PAA membrane) is sandwiched between two poly(lactic-co-glycolic acid) (PLGA) electrospun membranes as a novel sandwich-structured PLGA and PAA composite electrospun membrane (PLGA-PAA membrane) to resolve the need for sustained-release design and anti-inflammatory effects. Contact angle measurements indicate that the PLGA-PAA membrane is more hydrophilic than the PAA membrane. An in vitro release study reveals that PLGA membranes coated on PAA membrane could slightly slow down ion release, while significantly prolonging aspirin release. We also co-cultured membranes with dental pulp stem cells (DPSCs) and human monocytic THP-1 cells to evaluate their osteogenic ability and anti-inflammatory effects, respectively. Compared with the PAA membrane, the PLGA-PAA membrane promotes cell adhesion, proliferation, and osteogenic differentiation. A prolonged anti-inflammatory effect of up to 18 days is also observed in the PLGA-PAA group. The results suggest a promising strategy for fabricating an electrospun membrane system with controlled release capabilities and long-term anti-inflammatory effects for use as pulp-capping material for regeneration of the dentin-pulp complex.

Introduction In parallel with the improvement of living standard, Non-alcoholic fatty liver disease (NAFLD) becomes the most common liver disease around the world. Huazhi Fugan Granules (HZFGG) is a formula which is used to treating of fatty liver, Based on the data we studied, HZFGG may have potential as a therapeutic formula for the alleviation of NAFLD. Objectives The aim of our study was to identifying the improvement of HZFGG on NAFLD and exploring the potential mechanisms. Methods MCD diet fed C57BL/6 mice once a day for 4 weeks to induce NAFLD model, HZFGG (10, 15, 20 g/kg) orally administered simultaneously. The serum levels of TC, TG, ALT, AST were detected. H&E and Oil Red O staining were used to observed the liver sections. TNF-α, IL-1β and Gpx were also detected. The expression levels of TLR4, MyD88, p-NF-κB, NF-κB, p-IκBa were measured by western blotting assay. The apoptosis of the liver tissues were detected by TUNEL assay. Results HZFGG decreased the serum levels of TC, TG, ALT, AST in MCD-diet mice. HZFGG alleviated inflammation by decreasing the levels of TNF-α and IL-1β and ameliorated oxidative stress through increased the level of Gpx. HZFGG Attenuates MCD-induced liver steatosis and injury in mice. Hepatocyte apoptosis was decreased after HZFGG treatment. Furthermore, HZFGG also suppressed the expression levels of TLR4 and MyD88, subsequently, inhibited the phosphorylation of NF-κB and IκBa. Conclusion HZFGG can improved MCD induced hepatic injury through inhibited TLR4/NF-κB signaling pathway in NAFLD model.

Uridine diphosphate (UDP)-glycosyltransferases (UGTs), which are major phase II detoxification enzymes, have been implicated in the glycosylation of lipophilic endobiotics and xenobiotics and thus potentially lead to the evolution of insecticide resistance. In this study, we identified and cloned two putative UGT genes from transcriptome data which are named UGT352A4 and UGT352A5. As demonstrated by qRT-PCR, two UGT genes were over-expressed in the thiamethoxam-resistant (THQR) strain relative to the susceptible (THQS) strain. Moreover, the induction experiment revealed that the expression of the UGT352A5 gene was significantly increased following exposure to thiamethoxam in the THQR strain. Furthermore, the expression of both UGT352A4 and UGT352A5 was downregulated after RNA interference, whereas only the silencing of UGT352A5 resulted in a noticeable increase in the mortality of THQR adults. Our results represent the first line of evidence showing that UGT352A5 might be responsible for conferring thiamethoxam resistance in B. tabaci. The results will be shed new insights for obtaining a better understanding of the role of UGTs in the evolution of insecticide resistance and developing new insect resistance management tactics within the sustainable integrated pest management framework.

The ERF-type transcription factors (TFs) play vital roles in plant secondary metabolism. ERF TFs simultaneously regulate the expression levels of key enzyme genes involved in the biosynthesis of secondary metabolites due to its “multi-point control” function. In this study, one gene of ERF TFs from Panax japonicus (PjERF1) was cloned. The open reading frame of PjERF1 was 801 bp and encoded 266 amino acids. Phylogenetic analysis showed that PjERF1 belonged to ERF subfamily with a typical conserved domain. Subcellular localization found that PjERF1 protein might be located in eukaryotic cell nucleus. Yeast one-hybrid assay demonstrated that PjERF1 could bind to the promoters of PjβAS, PjCAS, and PjSE specifically and regulate the expression levels of such key enzyme genes involved in the triterpene saponins biosynthesis. Therefore, in the PjERF1 overexpression cell lines, the expression levels of some key enzyme genes involved in the triterpenoid saponins biosynthesis were significantly increased compared with those in non-transgenic cell line. As a result of it, the biosynthesis of chikusetsusaponin IV and IVa, and other ginsenosides (Rd, Rb1, Re, and R0) were also promoted in the PjERF1 overexpression cell lines. This study indicated that PjERF1 could regulate the biosynthesis of saponins in P. japonicus through controlling the expression levels of key enzyme genes related to the biosynthesis of triterpenoid saponins.

Two new sesquiterpenoids, 1–2, together with three known compounds, were isolated from Trichoderma hypoxylon. Among the known compounds, compound 4 was isolated as naturally occurring compound for the first time. The structures of these new compounds were characterized by HR-ESI-MS and spectroscopic methods including 1D and 2D NMR. The absolute configurations of 1–2 were assigned by electronic circular dichroism (ECD) calculations.

Aluminum borate porous ceramics are excellent candidates for high-temperature insulation applications. Current research on aluminum borate-based porous ceramics mainly focuses on porous ceramics made up of aluminum borate whiskers, whose low aspect ratio leads to a relatively dense porous structure; this results in porous ceramics with low porosity and relatively high thermal conductivity. In this study, we report the manufacturing of aluminum borate nanofibrous porous ceramics by an agar-based gel casting method using electrospun nanofibers with a high aspect ratio as the three-dimensional skeleton structure. We explored the effect of the alumina/boron oxide molar ratio on the microscopic morphology and crystal phase composition of the aluminum borate nanofibers and that of the sintering temperature on the micro and macro properties of porous ceramics based on the nanofibers. The results showed that aluminum borate nanofibers with an alumina/boron oxide molar ratio of 7:2 had the densest microscopic morphology, and the corresponding porous ceramics exhibited a higher porosity (91%) and lower thermal conductivity (0.11 W m−1 K−1) after sintering at 1200 °C than aluminum borate porous ceramics with aluminum borate whiskers as the skeleton. The successful synthesis of aluminum borate nanofibrous porous ceramics provides new insights into the development of high-temperature insulators.

To achieve carbon neutrality by 2060, decarbonization in the energy sector is crucial. Hydrogen is expected to be vital for achieving the aim of carbon neutrality for two reasons: use of power-to-hydrogen (P2H) can avoid carbon emissions from hydrogen production, which is traditionally performed using fossil fuels; Hydrogen from P2H can be stored for long durations in large scales and then delivered as industrial raw material or fed back to the power system depending on the demand. In this study, we focus on the analysis and evaluation of hydrogen value in terms of improvement in the flexibility of the energy system, particularly that derived from hydrogen storage. An electricity–hydrogen coupled energy model is proposed to realize the hourly-level operation simulation and capacity planning optimization aiming at the lowest cost of energy. Based on this model and considering Northwest China as the region of study, the potential of improvement in the flexibility of hydrogen storage is determined through optimization calculations in a series of study cases with various hydrogen demand levels. The results of the quantitative calculations prove that effective hydrogen storage can improve the system flexibility by promoting the energy demand balance over a long term, contributing toward reducing the investment cost of both generators and battery storage and thus the total energy cost. This advantage can be further improved when the hydrogen demand rises. However, a cost reduction by 20% is required for hydrogen-related technologies to initiate hydrogen storage as long-term energy storage for power systems. This study provides a suggestion and reference for the advancement and planning of hydrogen storage development in regions with rich sources of renewable energy.

To study the cell proliferation and wound healing activity of polysaccharides from Ganoderma amboinense (GAMPS), the polysaccharide was extracted by water extraction and alcohol precipitation method, and its monosaccharide composition and molecular weight were analyzed. The effects of different concentrations of GAMPS on the cell proliferation were determined by cell survival rate test, and the wound healing ability of GAMPS to NIH/3T3 cells was detected. The preliminary evaluation of the antioxidant ability of GAMPS was conducted by the oxygen radical absorbance capacity (ORAC). The results showed that the GAMPS was composed of glucose, mannose, and galactose at a molar ratio of 67.62:14.07:7.50, and the weight-average molecular weights were 5.439 × 106 and 1.704 × 105 g/mol by using high-performance gel-permeation chromatography-multiple angle laser scatter (HPGPC-MALS) analysis. GAMPS (0.2 μg/μL) showed the strongest proliferation ability to THP-1 cells, with cell survival rate of 178.7%. The wound healing effect of GAMPS (0.1 μg/μL) was obvious on NIH/3T3 and 3.75 μg/μL of GAMPS showed the strongest total antioxidant ability. All the results indicate that GAMPS promotes cell proliferation, and has cell wound healing effect and strong antioxidant activity. The results provide theoretical foundation for the development and utilization of GAMPS.

Diabetic cardiomyopathy (DCM) is one of the leading causes of heart failure in patients with diabetes mellitus, with limited effective treatments. The cardioprotective effects of sodium‐glucose cotransporter 2(SGLT2) inhibitors have been supported by amounts of clinical trials, which largely fills the gap. However, the underlying mechanism still needs to be further explored, especially in terms of its protection against cardiac fibrosis, a crucial pathophysiological process during the development of DCM. Besides, endothelial‐to‐mesenchymal transition (EndMT) has been reported to play a pivotal role in fibroblast multiplication and cardiac fibrosis. This study aimed to evaluate the effect of SGLT2 inhibitor dapagliflozin (DAPA) on DCM especially for cardiac fibrosis and explore the underlying mechanism. In vivo, the model of type 2 diabetic rats was built with high‐fat feeding and streptozotocin injection. Untreated diabetic rats showed cardiac dysfunction, increased myocardial fibrosis and EndMT, which was attenuated after treatment with DAPA and metformin. In vitro, HUVECs and primary cardiac fibroblasts were treated with DAPA and exposed to high glucose (HG). HG‐induced EndMT in HUVECs and collagen secretion of fibroblasts were markedly inhibited by DAPA. Up‐regulation of TGF‐β/Smad signalling and activity inhibition of AMPKα were also reversed by DAPA treatment. Then, AMPKα siRNA and compound C abrogated the anti‐EndMT effects of DAPA in HUVECs. From above all, our study implied that DAPA can protect against DCM and myocardial fibrosis through suppressing fibroblast activation and EndMT via AMPKα‐mediated inhibition of TGF‐β/Smad signalling.

High cost of lignocellulases restricts the commercialization of biofuel and bio‐product production from lignocellulosic biomass. Constitutively expressed lignocellulases are considered to degrade cellulose to release small amount of soluble cellodextrins such as cellobiose for further large‐scale production of lignocellulases; however, the underlying mechanism remains to be elucidated. Here, a triple β‐glucosidase mutant of the model fungus Neurospora crassa, which prevents rapid turnover of cellobiose and thus allows the disaccharide to induce lignocellulases, was applied to perform parallel analyses of proteome and phosphoproteome changes in response to cellobiose and Avicel cellulose. The results revealed shared proteome and phosphoproteome responses to cellobiose and Avicel, corroborating the idea that cellobiose mediates the regulation of lignocellulase expression and secretion. The results further suggest that this regulation is achieved at multiple levels, including epigenetic, transcription, post‐transcription, translation, and post‐translation. Proteome profiling revealed that the proteins upregulated by cellobiose and Avicel were over‐represented in cellulose degradation and degradation product transport pathways. Phosphoproteome profiling revealed that the proteins differentially phosphorylated by cellobiose and Avicel were over‐represented by the pathways such as transcriptional control, protein processing and export, cell wall biogenesis, and cellular signaling. Deletion mutation analysis further suggests that the ER chaperon protein Hsp70‐6, the translocation complex subunit Sec66/Sec71, and the signal peptidase subunit Spc2 are involved in lignocellulase secretion, particularly translocation across the endoplasmic reticulum. Altogether, the results offer a new insight into how cellobiose mediates the regulation of lignocellulase expression and secretion, providing a potential strategy for the strain engineering to improve lignocellulase production.

Conjugated polymers with well-balanced ambipolar charge transport is essential for organic circuits at low cost and large area with simplified fabrication techniques. Aiming at this point, herein, a novel asymmetric thiophene/pyridine-flanked diketopyrrolopyrrole-based copolymer (PPyTDPP–2FBT) is designed and synthesized. Due to the effect of incorporating F atoms on molecular energy alignment and conjugation conformation, the PPyTDPP–2FBT copolymer exhibits typical V-shaped ambipolar field-effect transfer characteristics with well-balanced hole and electron mobilities of 0.64 and 0.46 cm2 V−1 s−1, respectively. Furthermore, organic digital and analog circuits such as inverters and frequency doublers are successfully constructed based on solution-processed films of the PPyTDPP–2FBT copolymers which show a typical circuit operating mode with a high gain of 133 due to the well-balanced electrical properties. In addition, PPyTDPP–2FBT-based devices also demonstrate good stability and batch repeatability, suggesting their great potential applications in organic integrated electronic circuits.

Functional dyspepsia (FD) is a common disease of the digestive system and probiotics have been reported to be effective in the treatment of functional gastrointestinal diseases. The aim of this study was to determine the effect of the beverage containing Lactobacillus paracasei LC-37 (LC-37) and its ability to relieve symptoms of FD by a randomized clinical trial. Due to the mechanistic complexity underlying FD, intestinal microbiota and stool metabolomes were also evaluated. The results showed that FD was relieved in participants after treatment with the beverage containing LC-37 for 14 and 28 d. The clinical symptom scores were significantly decreased after these times (abdominal pain and belching were significantly decreased after 14 d and almost absent after 28 d of treatment). Probiotics, such as those containing the Lactobacillus, Lactococcus, and Weissella, significantly increased, and the abundance of harmful bacteria such as Lachnocliostridium significantly decreased. Furthermore, relevant beneficial intestinal metabolites such as pelargonic acid, benzoic acid, and short-chain fatty acids increased, and harmful intestinal metabolites such as hippuric acid decreased. Taken together, these findings suggested that the beverages containing LC-37 can increase the abundance of probiotics and decrease pathogenic bacteria, and thereby improve beneficial intestinal metabolites. Therefore, the beverages containing LC-37 may provide a natural alternative to combat FD.

The effect of atomic-layer-deposition (ALD)-derived Al2O3 passivation layer on the interface quality of Er2O3/Al2O3/InP laminated stacks and the improvement of electrical performance has been investigated systematically. The chemical bonding states measured by high-resolution X-ray photoelectron spectroscopy (XPS) reveal that the ALD-derived Al2O3 passivation layer can effectively inhibit the diffusion of substrate elements to optimize the interface quality. Electrical characterizations show that the optimized sample has demonstrated improved electrical properties, including the large dielectric constant of 20 and the suppressed leakage current density of $4.10\times 10^{-7}$ cm2. In addition, the leakage current conduction mechanisms are also investigated as a function of thickness of Al2O3 passivation layer. The optimized interface state density extracted from the conductance method has reduced from $1.30 \times 10^{12}$ eV−1cm2 of Er2O3/InP to $7.27 \times 10^{11}$ eV−1cm2 of Er2O3/Al2O3/InP by adjusting the passivation layer thickness. As a result, it can be also confirmed that the passivation treatment is beneficial to inhibit the element’s diffusion and optimize the interface quality, significantly controlling the capacitor degradation caused by the leakage current through the stacked oxide layer.

Human serum albumin (HSA), a versatile protein carrier for endogenous and exogenous compounds, is a proven macromolecule to form nanoparticles for drug delivery. To render HSA carrier specificity toward tumors, we designed a recombinant HSA protein fused with Kunitz domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 1, which targets to matriptase, a type II transmembrane serine protease overexpressed on tumor cell surface. The carrier was thus named matriptase targeting carrier (MTC). In this study, we showed that MTC displayed the same inhibitory potency as the KD1 againast matriptase, demonstrating the HSA fusion did not affect the KD1 targeting potency. For tumor optical imaging and ablation, MTC was prepared as nanoparticle drug carrier by a novel method via denaturation and refolding to incorporate photosensitizer, CPZ. This matriptase targeting nanoparticles, CPZ:MTC@NPs, showed high specificity and cytotoxicity for matriptase-overexpressing cancer cells in vitro. In tumor-bearing mice, CPZ:MTC@NPs demonstrated selective accumulation and high retention in matriptase-overexpressing tumor. Under illumination, the nanoparticles significantly reduced tumor volumes (79.6%) as compared to saline control. These findings showed that this supramolecular nanocarrier, a new type of tumor targeting self-assembly nanoparticle, had potential as a highly efficient tumor targeting drug carrier for imaging and therapy.

An efficient regioselective palladium(II)-catalyzed C(sp2)-H 4-acetoxylation of tryptophan and tryptophan-containing peptides is described. This transformation achieves the direct construction of C-O bonds at the tryptophan C4-position and features good functional group tolerance. The 4-hydroxyl compound was obtained by removing acetyl after C4-acetoxylation of tryptophan derivatives and tryptophan-containing dipeptides. This method provides a novel strategy for the synthesis of 4-substituted tryptophan derivatives and modification of tryptophan-containing peptides.

Perchlorate (ClO4-) is a pervasive, harmful, and inert anion on both Earth and Mars. Current technologies for ClO4- reduction entail either harsh conditions or multicomponent enzymatic processes. Herein, we report a heterogeneous (L)Mo-Pd/C catalyst directly prepared from Na2MoO4, a bidentate nitrogen ligand (L), and Pd/C to reduce aqueous ClO4- into Cl- with 1 atm of H2 at room temperature. A suite of instrument characterizations and probing reactions suggest that the MoVI precursor and L at the optimal 1:1 ratio are transformed in situ into oligomeric MoIV active sites at the carbon-water interface. For each Mo site, the initial turnover frequency (TOF0) for oxygen atom transfer from ClOx- substrates reached 165 h-1. The turnover number (TON) reached 3840 after a single batch reduction of 100 mM ClO4-. This study provides a water-compatible, efficient, and robust catalyst to degrade and utilize ClO4- for water purification and space exploration.

This manuscript describes the chemical process development and multi-kilogram synthesis of rovafovir etalafenamide (GS-9131), a phosphonamidate prodrug nucleotide reverse transcriptase inhibitor un...

Fluorinated nucleoside 1 is a key starting material in the synthesis of rovafovir etalafenamide (2), a novel nucleotide reverse transcriptase inhibitor under development at Gilead Sciences for the ...

Phosphonamidate 1 is a key fragment in the assembly of rovafovir etalafenamide, a novel nucleotide reverse transcriptase inhibitor under development at Gilead Sciences for the treatment of HIV infe...

Due to the low intrinsic hole mobility caused by the orthogonal conformation of two fluorene units in Spiro-OMeTAD which is a classic hole-transporting material (HTM) in perovskite solar cells (PSCs), Spiro-OMeTAD based PSCs generally can only obtain high performances through a sophisticated doping process with dopants/additives, which adds to the cost and complicacy of device fabrication, and also adversely affects the stability of PSC devices. Herein, a novel dispiro-based HTM, WH-1, is designed by cleverly replacing the central carbon atom of Spiro-OMeTAD with cyclohexane, and the spatial configuration of the HTM is changed from vertical orthogonality of the two fluorene units to a parallel arrangement, which is beneficial for the formation of a homogeneous and compact HTM film on the surface of the perovskite film, improvement of intermolecular electronic coupling and intrinsic hole mobility. WH-1 is obtained by two-step facile synthesis with a high yield from commercially available materials. WH-1 is used in PSCs as a dopant-free HTM, which is the first time that the dispiro-based molecule has been applied as a dopant-free HTM, and a power conversion efficiency (PCE) of 19.57% is obtained, rivaling Li-TFSI/t-BP doped Spiro-OMeTAD in PCE (20.29%), and showing obvious superior long-term stability., A dispiro-based HTM with a parallel arrangement of two fluorenes was designed by replacing the central carbon atom of Spiro-OMeTAD with cyclohexane. The PCE of a PSC based on dopant-free WH-1 is 19.57%, rivaling that of doped Spiro-OMeTAD (20.29%).

The morphology of catalysts is a key factor influencing their photocatalytic performance. Herein, we prepared three W18O49 photocatalysts with different morphologies of sea urchin (W18O49SU), nanorod (W18O49NR) and hollow sphere (W18O49HS), and evaluate their performances in photocatalytic hydrolysis of ammonia borane (AB). Remarkably, W18O49SU exhibited an impressive photocatalytic H2 production rate with the highest TOF of 53.1 min−1 under visible light, which is 10.4 and 7.5 times higher than those of W18O49HS and W18O49NR, respectively. The comprehensive characterizations and control experiments revealed that the unique sea urchin-like morphology enabled the strong light harvesting by multiple light scattering, fast separation of photogenerated charges and directional electron enrichment by nanotip effect, which collaboratively boost the photocatalytic activity. Moreover, the enhancement effect of sea urchin-like morphology is again approved well on Nb2O5 photocatalysts. This work opens a paradigm to synergistically improve light harvesting and charge separation efficiency through rational design of photocatalyst nanostructure.