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The vinyltrimethoxysilane was utilized to modify the surface of α-AlH3 by a simple surface coating method. The α-AlH3@A171 composite obtained presents excellent stability, regarded as a potential fuel in the field of solid propellants.

The low-temperature CO + NH3 coupling denitration of the Mn/AC catalyst conforms to the L–H mechanism when the temperature is lower than 230 °C and the E–R mechanism when the temperature is higher than 230 °C.

Zn slats compete with CO and NO for the active sites. Cl− not only occupies oxygen vacancies but also inhibits the Oβ migration. SO42− increases the surface acidity and promotes the Oβ supplementation, which inhibits toxicity.

This study aims to explore the influence mechanism of ammonium nitrate produced by ozone denitrification on the crystallization of ammonium sulfate, a by-product of ammonia desulfurization. The laser method was used to study the influence of ammonium nitrate on the solubility and metastable zone width of ammonium sulfate. An experiment on the influence of ammonium nitrate on the particle size of ammonium sulfate was designed, and the influence mechanism was explored through scanning electron microscopy and X-ray diffraction. The findings showed that the addition of ammonium nitrate increased the size and aspect ratio of ammonium sulfate crystals. The addition of ammonium nitrate inhibited the dissolution of ammonium sulfate and widened its metastable zone. The addition of ammonium nitrate covered the active sites of crystal nucleus growth, which inhibited the formation of crystal nuclei to a certain extent, and crystal growth dominated the crystallization process. Moreover, the addition of ammonium nitrate induced the preferred orientation of the specific crystal plane of ammonium sulfate, and the addition of a small concentration of ammonium nitrate decreased the crystallinity of ammonium sulfate. The research results can provide a reference for crystallization optimization and quality improvement of ammonium sulfate in the ammonia desulfurization process.

Anaplastic thyroid carcinoma (ATC) is the most lethal thyroid carcinoma. Doxorubicin (DOX) is the only drug approved for anaplastic thyroid cancer treatment, but its clinical use is restricted due to irreversible tissue toxicity. Berberine (BER), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has been proposed to have antitumor activity in many cancers. However, the underlying mechanisms by which BER regulates apoptosis and autophagy in ATC remain unclear. Thus, the present study aimed to assess the therapeutic effect of BER in CAL-62 and BHT-101 cells as well as the underlying mechanisms. In addition, we assessed the antitumor effects of a combination of BER and DOX in ATC cells. The present results showed that BER significantly inhibited cell growth and induced apoptosis in ATC cells. BER treatment also significantly upregulated the expression of LC3B-II and increased the number of GFP-LC3 puncta in ATC cells, suggesting that BER induced a high level of autophagy. Inhibition of autophagy by 3-methyladenine (3-MA) suppressed BER-induced autophagic cell death, which confirmed the anticancer role of autophagy induced by BER. Moreover, BER induced the generation of reactive oxygen species (ROS). N-acetylcysteine (NAC), a potential ROS scavenger, substantially suppressed the expression of autophagy-regulated proteins and apoptosis proteins induced by BER. Moreover, BER and DOX cooperated to promote apoptosis and autophagy in ATC cells. Mechanistically, we demonstrated that BER regulated the autophagy and apoptosis of human ATC cells through the PI3K/AKT/mTOR pathways. Taken together, the present findings indicated that BER induces apoptosis and autophagic cell death by activating ROS and regulating the PI3K/AKT/mTOR signaling pathway.

This paper presents a novel seamless switching technology between different operating conditions of the Unified Power Quality Conditioner (UPQC) with the energy storage system. Frequent start and stop of the series inverter will cause shock and loss under the conventional control method. Moreover, it is a key issue to achieve seamless switching when the UPQC operating condition changes. This paper proposes an improved power angle control (PAC) method to solve these problems. An agile power angle is calculated by this method under stable operating conditions. This feature enables the series inverter to share the load reactive power with the shunt inverter. On the other hand, both the series and shunt inverters are in an easy-to-switch operating state which can help achieve better seamless switching between different operating conditions. Simulation results show the shunt inverter capacity can be reduced up to 47% due to the reactive power sharing by both the inverters which means the reactive power burden of the shunt inverter is great lightened. It is also found that the switching time is about 300μs faster and the maximum voltage fluctuation amplitude is about 90V smaller under improved PAC than the conventional control method.

Liver fibrosis is the most common pathway in most types of chronic liver damage, characterized by an imbalance of ECM degradation and synthesis. Saikosaponin-d (SSd) possesses anti-inflammatory and anti-fibrotic effects. However, the underlying mechanism by which SSd represses hepatic stellate cell (HSC) activation remains unclear. Here, we found that SSd remarkably alleviated carbon tetrachloride (CCl4)-induced liver fibrosis, as evidenced by decreased collagen levels and profibrotic marker (COl1a1 and α-smooth muscle actin (SMA)) expression. SSd repressed CCl4-induced NOD-like receptor family pyrin-domain-containing-3 (NLRP3) activation in fibrotic livers, as suggested by decreased levels of NLRP3, IL-18, and IL-β. The primary HSCs of CCl4 mice exhibited a significant increase in profibrotic marker expression and NLRP3 activation, but SSd treatment reversed this effect. SSd also repressed TGF-β-induced profibrotic marker expression and NLRP3 activation in vitro. Mechanistically, TGF-β decreased the expression of estrogen receptor-β (ERβ) in HSCs, whereas SSd treatment reversed this effect. ERβ inhibition enhances NLRP3 activation in HSCs. More importantly, ERβ or NLRP3 inhibition partially destroyed the function of SSd in liver fibrosis. In summary, the current data suggest that SSd prevents hepatic fibrosis by regulating the ERβ/NLRP3 inflammasome pathway and suggests SSd as a potential agent for treating liver fibrosis.

We propose a feature color extraction method that improves the accuracy of water quality analysis using a digital image and eliminates the effect of interfering ions and chromogenic agents on the color after a color reaction. The proposed method is based on color deconvolution (CD) combined with machine learning for substance measurement in water. After an ordinary camera acquires the solution image after color reaction, the CD algorithm is applied to extract the feature image, calculate the first-order, second-order, and third-order color moments corresponding to RGB channels, and construct a gradient boosting regression tree prediction model based on color moment features to detect substances in water. In predicting ammonia, nitrite, and orthophosphate concentrations, the mean square error values were 0.01029, 0.00063, and 0.1361, and the mean absolute error values were 0.08103, 0.02231, and 0.32886, respectively. There was no significant difference in the results of the comparative spectrophotometric method on the actual water samples. The spiked recoveries of the samples ranged from 94% to 120%, confirming that the method can effectively measure the content of substances in water.

Background: Cerebrospinal fluid (CSF) shunt intervention is currently the standard and most effective treatment for idiopathic normal-pressure hydrocephalus (iNPH). However, many patients do not undergo surgery due to various reasons. The study aimed to assess the efficacy and safety of methazolamide (MTZ) in the treatment of iNPH. Methods: A 12-week randomized, double-blind, drug-placebo clinical studywas conducted at the Aviation General Hospital. Participants with a diagnosis of possible or probable iNPH according to Japanese second iNPH guidelines were consecutively recruited from September 2019 to May 2021. All patients were inoperable or had refused surgical treatment due to various reasons. The patients were assigned (2:1) to the MTZ or placebo group via a computer-generated randomization list. The gait and cognition function were assessed, and brain MRI scans were taken before and 12 weeks after drug administration. The primary endpoint was the difference change in the Boon gait sum score relative to baseline between the drug and placebo groups. Secondary endpoints were differences in MMSE and MOCA scores. In addition, the adverse reactions were also monitored. Results: Twenty participants were randomly included in the MTZ group and 12 in the placebo group. A total of 26 patients, 17 in the MTZ and 9 in the placebo group, were included in the final efficacy analysis. The difference in Boon sum score relative to baseline between the groups was -6.06 points (95% CI, -9.37 to -2.75; p =0.001) after 12 weeks of treatment. However, there was no significant difference in the MMSE and MoCA scores between the drug and placebo groups (MMSE 0.36, 95% CI, -2.36 to 3.09; p = 0.78; MoCA 0.001, 95% CI, -1.98 to 1.98; p = 1.00). No serious adverse reactions such as hypokalemia or acidosis occurred in any of the patients. Conclusions: MTZ significantly improved the gait of iNPH patients without any adverse effects. Large sample studies are needed for further confirmation of our results.

To explore the mechanism of low-temperature carbon monoxide and ammonia (CO + NH

With the rising need for energy resources, considerable work has done for building novel energy storage technologies. Supercapacitors (SCs) and batteries are a highly competitive choice for electrochemical energy storage devices (EESDs) due to their ultrahigh power density, improved rate capability, long-term cyclability, and remarkable safety. Because of their novel properties such as high mechanical flexibility, large specific surface area (SSA), chemical stability, and superior electric and thermal conductivities, graphene-based nanomaterials (NMs) have attracted considerable attention as alternative electrode materials for EESDs. Graphene is gaining a lot of interest since it has amazing qualities including 230 000 cm2 V-1 s-1 charge mobility, 3000 W m-1 K-1 thermal conductivity, 2.3% visible light absorption, 130 GPa mechanical strength, and 2600 m2 g-1 specific surface area (SSA). Mechanical exfoliation, reduction of graphene-oxide, chemical vapor deposition (CVD), and epitaxial growth of graphene-NMs are some of the synthetic procedures that can change these characteristics. Despite much effort, the detailed screening of high-performance electrode materials, such as graphene-based NMs, is still necessary. We covered the recent advancements in graphene-based NM research and development for high-performance batteries and SCs for specific applications in the next generation and smart electronics in this study. First, we discuss rechargeable batteries, a new-concept based on graphene with high energy density, longer life, improved safety, and shape-diversity capabilities in order to meet the needs of future electronics. Second, we discuss SCs for the present advanced nanotechnologies that outperform batteries with respect to power density, cyclability, quick charging/discharging rates capability, straightforward principles, high activity of the charge circulation, and low maintenance expenditure, including electrical double layer capacitors (EDLCs) and pseudocapacitors (PCs). Finally, graphene-based electrodes used in ESDs with their prospects and problems are briefly reviewed.

The constitutive androstane receptor (CAR), a known xenobiotic sensor, plays an important role in drug metabolism by regulating numerous genes. The polycyclic aromatic hydrocarbon pyrene, an environmental pollutant, is a CAR activator and induces mouse hepatotoxicity via CAR. Here, we investigate the molecular mechanisms of the inflammatory response in pyrene-caused mice liver injury.Effects of pyrene on the liver were investigated in wild-type and CAR knockout (KO) mice. Levels of pyrene and its urinary metabolite were analysed by high performance liquid chromatography (HPLC). Inflammatory responses were measured by qRT-PCR, western blotting, and ELISA for cytokines.Serum amyloid A proteins (SAAs) were markedly increased in the liver and serum of pyrene-exposed wild-type mice. IL-17-producing helper T cells (Th17 cells) and IL-17 levels were increased in the liver of pyrene-exposed wild-type mice. Hepatic mRNA levels of inflammatory cytokines including IL-1β, IL-6 and TNFα, and serum IL-6 levels were significantly elevated in pyrene-treated wild-type mice. However, these changes were not observed in CAR KO mice.CAR plays a crucial role in pyrene-caused mice liver inflammatory response with increased SAAs and Th17 cells. Our results suggest that serum SAAs may be a convenient biomarker for early diagnosis of liver inflammatory response caused by polycyclic aromatic hydrocarbons, including pyrene. CAR and Th17 cells may be potential targets for novel therapeutic strategies for xenobiotic-induced liver inflammation.

Although cancer diagnosis research has continuously made breakthroughs in a single indicator, it is a challenging task to improve its multiple joint indicators. This study proposes a multi-category multi-state information ensemble-based classification method. We fuse protein-coding and non-coding genes to construct co-expression profiles, which ensemble the field information of classical genetics and epigenetics. A hierarchical feature selection algorithm based on control groups is put forward to quickly remove irrelevant and redundant features without the bias caused by unbalanced dataset. Multiple heterogeneous diagnosis models, which ensemble multiple diagnosis model structures and model states, are constructed and a competition mechanism is then introduced to automatically select the best model from multiple heterogeneous models without deeply grasping the positive and negative fusion effects between different algorithms and features. We apply the proposed method to classify three high-incidence cancers, in which the classification accuracy and sensitivity are over 99.23% and the classification specificity is over 97.37%. This illustrates that the proposed method has upgraded the three joint indicators of cancer diagnosis at the same time. Compared with the state-of-the-art classification methods, the classification accuracy has been improved by 2.23–9.23%, the sensitivity by 6.25–37.40%, and the specificity by 0–12.02%. In addition, feature analysis reveals three biological findings.

Two-dimensional (2D) selenium was synthesized successfully in 2017. Its advanced properties, including size-dependent bandgap, excellent environmental robustness, strong photoluminescence effect, anisotropic thermal conductivity, and high photoconductivity, render it and selenium-based composites a promising candidate for various device applications. These include batteries, modulators, photodetectors, and photothermal effects in medical applications. However, compared to other commonly used 2D materials, such as graphene, transition metal dichalcogenides, and black phosphorus, 2D Se is much less known. Motivated by the need to overcome this lack of knowledge, this article focuses on recent progress and elucidates the crystal structure, synthesis methods, physical properties, applications, challenges, and prospects of 2D Se nanoflakes.

The controlled introduction of elastic strains is an appealing strategy for modulating the physical properties of semiconductor materials. With the recent discovery of large elastic deformation in nanoscale specimens as diverse as silicon and diamond, employing this strategy to improve device performance necessitates first-principles computations of the fundamental electronic band structure and target figures-of-merit, through the design of an optimal straining pathway. Such simulations, however, call for approaches that combine deep learning algorithms and physics of deformation with band structure calculations to custom-design electronic and optical properties. Motivated by this challenge, we present here details of a machine learning framework involving convolutional neural networks to represent the topology and curvature of band structures in k-space. These calculations enable us to identify ways in which the physical properties can be altered through “deep” elastic strain engineering up to a large fraction of the ideal strain. Algorithms capable of active learning and informed by the underlying physics were presented here for predicting the bandgap and the band structure. By training a surrogate model with ab initio computational data, our method can identify the most efficient strain energy pathway to realize physical property changes. The power of this method is further demonstrated with results from the prediction of strain states that influence the effective electron mass. We illustrate the applications of the method with specific results for diamonds, although the general deep learning technique presented here is potentially useful for optimizing the physical properties of a wide variety of semiconductor materials. Nanyang Technological University Published version The computations involved in this work were conducted on the computer cluster at Skolkovo Institute of Science and Technology (Skoltech) CEST Multiscale Molecular Modelling group and Massachusetts Institute of Technology (MIT) Nuclear Science Engineering department. E.T., Z.S., A.S., and J.L. acknowledge support by the Skoltech-MIT Next Generation Program 2016-7/NGP. E.T. and A.S. acknowledge support by the Center for Integrated Nanotechnologies, an Office of Science User Facility operated for the U.S. Department of Energy Office of Science by Los Alamos National Laboratory (Contract 89233218CNA000001) and Sandia National Laboratories (Contract DE-NA-0003525). M.D. acknowledges support from MIT J-Clinic for Machine Learning and Health. S.S. acknowledges support from Nanyang Technological University through the Distinguished University Professorship.

Fe-loaded activated carbon (AC) has high surface acidity and more active sites, while manganese-loaded AC has high oxygen content. Coconut husk AC modified by Fe–Mn was studied with the aim of revealing the modification mechanism. First, HNO3/AC was prepared using the nitric acid immersion method. Second, Fe–Mn/AC was prepared using the Fe(NO3)3 and Mn(NO3)2 sequential immersion. The effects of HNO3, Fe(NO3)3, and Mn(NO3)2 on the pore texture and surface chemical characteristics of carbon materials were examined by scanning electron microscopy, Brunauer–Emmett–Teller (BET) analysis, X-ray diffraction and Fourier-transform infrared spectroscopy. The surface topography, pore structure, active material, and functional groups of AC, HNO3/AC, and Fe–Mn/AC were systematically studied. The following results were obtained. The surface of HNO3/AC has more ditches and air voids; the micropores of HNO3/AC are deformed and flattened compared to those of AC. The surface of Fe–Mn/AC exhibits an accumulation phenomenon. MnFe2O4 and FeMn2O4 formed more pore structures. AC and HNO3/AC have numerous micropores. The higher loading quantity of Fe–Mn results in bigger specific surface. The active components of Fe–Mn/AC-1, Fe–Mn/AC-2, Fe–Mn/AC-3, and Fe–Mn/AC-4 are MnFe2O4, Mn0.43Fe2.57O4, Mn3O4, and α-Fe2O3, respectively. The surface functional groups of AC and HNO3/AC are oxygen-containing functional groups. The effect of Fe–Mn modifying conditions on functional group species is rare; however, Fe/AC has more oxygen-containing functional groups. These research findings can aid in the desulfurization and denitrification of the Fe–Mn/AC catalyst.

By increasing the charging voltage, a cell specific energy of >400 W h kg−1 is achievable with LiNi0.8Mn0.1Co0.1O2 in Li metal batteries. However, stable cycling of high-nickel cathodes at ultra-high voltages is extremely challenging. Here we report that a rationally designed sulfonamide-based electrolyte enables stable cycling of commercial LiNi0.8Co0.1Mn0.1O2 with a cut-off voltage up to 4.7 V in Li metal batteries. In contrast to commercial carbonate electrolytes, the electrolyte not only suppresses side reactions, stress-corrosion cracking, transition-metal dissolution and impedance growth on the cathode side, but also enables highly reversible Li metal stripping and plating leading to a compact morphology and low pulverization. Our lithium-metal battery delivers a specific capacity >230 mA h g−1 and an average Coulombic efficiency >99.65% over 100 cycles. Even under harsh testing conditions, the 4.7 V lithium-metal battery can retain >88% capacity for 90 cycles, advancing practical lithium-metal batteries. Charging at high voltages in principle makes batteries energy dense, but this is often achieved at the cost of the cycling stability. Here the authors design a sulfonamide-based electrolyte to enable a Li metal battery with a state-of-the-art cathode at an ultra-high voltage of 4.7 V while maintaining cyclability.

Background: Targeting the estrogen receptor (ER) has proven to be one of the most successful strategies in treating HR+ (ER+ and PR+) and HER2- breast cancer. Selective estrogen receptor degraders (SERD) can be used as single agents or in combination with CDK4/6 inhibitors such as palbociclib. Fulvestrant is currently the only approved agent in its class and is limited by poor oral bioavailability necessitating monthly intramuscular injections. D-0502 is an orally bioavailable SERD with potent activity in various HR+ and HER2- breast cancer cell lines and xenograft models. Its combination with palbociclib in both MCF-7 xenograft models and ESR-1 mutated (Y537S) patient derived breast cancer xenograft models resulted in further tumor growth inhibition or regression. Drug metabolism and pharmacokinetic studies both in vitro and in vivo demonstrated that D-0502 exhibits favorable PK profiles suitable for clinical development. Methods: A first-in-human phase 1 study was conducted to evaluate D-0502 in women with advanced or metastatic HR+, HER2- breast cancer (MBC) (NCT03471663). The primary objective is to characterize the safety and tolerability of D-0502 and D-0502 in combination with palbociclib, to identify an MTD and/or RP2D. The secondary objectives are to evaluate the PK properties and the preliminary anti-tumor activities. Patients received D-0502 orally once daily in 28-day cycles. The study has completed dose escalation (phase 1a), and dose expansion and combination studies (phase 1b) are ongoing. In phase Ia, patients were enrolled and evaluated using conventional 3+3 dose-escalation to identify the MTD of D-0502 as a single agent. The phase 1b was divided into 2 stages. In Stage 1, D-0502 was evaluated with palbociclib at a dose below the MTD first before escalating to the MTD. Stage 1 also included patients in China treated at a dose below and at the MTD as single agent as well as in combination with palbociclib. Stage 2 will further evaluate the MTD for both single agent and combination of D-0502 with palbociclib. Results: At the time of this abstract submission, phase 1a dose escalation is completed, R2PD has been identified, and no DLTs were observed. PK analysis of D-0502 indicates a dose proportional increase in exposure as the dose increases, and the exposure has exceeded the potential therapeutic exposure level based on preclinical studies. The Phase Ib Stage 1 portion has also completed enrollment and the study is currently enrolling patients into phase Ib Stage 2. D-0502 as a single agent or in combination has been well tolerated with radiological tumor response and clinical benefit response (CBR) observed. Safety, PK and preliminary efficacy data will be reported at the meeting presentation. Conclusion: A first-in-human phase 1 study of D-0502 has been initiated in women with advanced or metastatic HR-positive and HER2-negative breast cancer. D-0502 has been well tolerated and achieved significant exposure and preliminary clinical activity in patients. Further results will be presented at the meeting. Citation Format: Cynthia Osborne, Donald A Richards, Sharon T Wilks, Sami Diab, Dejan Juric, Kate Lathrop, Andrea Silber, William Edenfield, Amardeep Aulakh, Ben Cho, Binghe Xu, Tao Sun, Quchang Ouyang, Yanxia Shi, Kathryn Stazzone, Zhe Shi, Ling Zhang, Yaolin Wang, Erika P Hamilton. A phase 1 study of D-0502, an orally bioavailable SERD, for advanced or metastatic HR-positive and HER2-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-26.

The GABAB receptor (GABABR) agonist baclofen has been used to treat alcohol and several other substance use disorders (AUD/SUD), yet its underlying neural mechanism remains unclear. The present study aimed to investigate cortical GABABR dynamics following chronic alcohol exposure. Ex vivo brain slice recordings from mice chronically exposed to alcohol revealed a reduction in GABABR-mediated currents, as well as a decrease of GABAB1/2R and G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) activities in the motor cortex. Moreover, our data indicated that these alterations could be attributed to dephosphorylation at the site of serine 783 (ser-783) in GABAB2 subunit, which regulates the surface expression of GABABR. Furthermore, a human study using paired-pulse-transcranial magnetic stimulation (TMS) analysis further demonstrated a reduced cortical inhibition mediated by GABABR in patients with AUD. Our findings provide the first evidence that chronic alcohol exposure is associated with significantly impaired cortical GABABR function. The ability to promote GABABR signaling may account for the therapeutic efficacy of baclofen in AUD.

This paper analyses the sequential mediation effects of managerial attitude towards risk and entrepreneurial behaviour on the relationship between dynamic capabilities and entrepreneurial performan...

Ultrathin and flexible layers containing BaTiO3 (BTO) nanoparticles, graphene oxide (GO) sheets, and carbon nanotube (CNT) films (BTO/GO@CNT) are used to trap solvated polysulfides and alleviate the shuttle effect in lithium-sulfur (Li-S) batteries. In the functional layers, the CNT films build a conductive framework, and the GO sheets form a support membrane for the uniform dispersion of BTO nanoparticles. BTO nanoparticles without ferroelectricity (nfBTO) can trap polysulfides more effectively by chemical interaction compared to BTO nanoparticles with ferroelectricity (fBTO). A Li-S cell with the nfBTO/GO@CNT functional layer exhibits a reversible capacity of 824.5 mA h g-1 over 100 cycles at 0.2 C. At a high sulfur loading of 5.49 mg cm-2, an electrode with the functional layer shows an areal capacity of 5.15 mA h cm-2 at 0.1 C, demonstrating the nfBTO/GO@CNT functional layer's potential in developing high-performance Li-S batteries.

The gas-solid-based synergistic reduction of pellets is an innovative and effective method for iron ore smelting. With the development and utilization of iron resources, ore reserves have been greatly depleted; therefore, as a scarce mineral resource, the comprehensive utilization of limonite has become increasingly important. To study the reduction kinetics of pellets in depth, this study used coke and reducing gases (CO and H2) to study the reduction characteristics and changes occurring in carbon-containing limonite pellets. The results showed that the total weight loss percentage of pellets gradually increased with the temperature. The C/O molar ratio had a greater effect on the total weight loss percentage of pellets in a N2 atmosphere, but it had no significant effect in CO or H2 atmospheres. The maximum reaction rate increased with increasing temperature. The reduction reaction was the most difficult to proceed in the N2 atmosphere, and the reaction was most likely to occur in the CO atmosphere. The analysis of pellets by EPMA and XRD found that the pellets reduced in the N2 atmosphere had the lowest porosity, and the pellets reduced in the H2 atmosphere had the highest porosity, which was more conducive to gas diffusion. Some of the unreduced Si, Al, Mn, Ca, and Fe in the pellets reduced in the N2 atmosphere precipitated in the form of oxides, but when a reducing gas (CO, H2) was introduced, precipitation did not occur.

Fire disturbance can affect the function of the boreal forest ecosystem through litter decomposition and nutrient element return. In this study, we selected the Larix gmelinii forest, a typical forest ecosystem in boreal China, to explore the effect of different years (3 years, 9 years, 28 years) after high burn severity fire disturbance on the decomposition rate (k) of leaf litter and the Carbon:Nitrogen:Phosphorus (C:N:P) stoichiometry characteristics. Our results indicated that compared with the unburned control stands, the k increased by 91–109% within 9 years after fire disturbance, but 28 years after fire disturbance the decomposition rate of the upper litter decreased by 45% compared with the unburned control stands. After fire disturbance, litter decomposition in boreal forests can be promoted in the short term (e.g., 9 years after a fire) and inhibited in the long term (e.g., 28 years after a fire). Changes in litter nutrient elements caused by the effect of fire disturbance on litter decomposition and on the C, N, and C:N of litter were the main litter stoichiometry factors for litter decomposition 28 years after fire disturbance. The findings of this research characterize the long-term dynamic change of litter decomposition in the boreal forest ecosystem, providing data and theoretical support for further exploring the relationship between fire and litter decomposition.

Titanium (Ti) implant-associated infections are a challenge in orthopedic surgery, for which a series of antibacterial coatings have been designed and fabricated to reduce the risk of bacterial contamination. Herein, we created a degradable three-layer sandwich-type coating to achieve long-term antibacterial effects while simultaneously reconstructing the local immune microenvironment. The vancomycin (Van)-loaded vaterite coating constitutes the outer and inner layers, whereas Interleukin-12 (IL-12)-containing liposomes embedded in sodium alginate constitutes the middle layer. Van, released from the vaterite, demonstrated a favorable and rapid bactericidal ability against the representative methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains. The released IL-12 exhibited the desired immune reconstitution abilities, actively facilitating defenses against subsequent bacterial invasions. Furthermore, the biocompatibility and cell-binding feature of the multifunctional coating was beneficial for achieving solid interface intergradation. Overall, the benefits of the three-layer sandwich-type coating, including the convenient fabrication process, efficient antimicrobial activity, fast immune remodeling property, fine cell-binding feature, and biodegradability, highlight its promising translational potential in preventing implant infection. STATEMENT OF SIGNIFICANCE: To prevent titanium implant infections, researchers have designed various antibacterial coatings. However, most of these coatings focused only on killing the invading bacteria over a limited postoperative period. However, the local immune microenvironment is compromised during surgery. Local immune deflection impedes the ability of the local immune defenses to clear bacteria and limits immune memory building from active defense against long-term subsequent bacterial invasions. Furthermore, these coatings are usually nondegradable and differ substantially from bone components, thereby impairing the integration of the coating and bone interface and generating concerns about implant stability and bacterial contamination. In this work, we synthesized a degradable coating that provides sustained antibacterial activity, promotes immune reconstitution, and simultaneously achieves solid bone integration.

Population-based studies of diabetes may be limited by sampling and capture. Our study utilizes the Ontario Diabetes Database, which captures all persons in Ontario, Canada with non-gestational diabetes. Based on sensitive and specific cohort definitions adults with T2DM were identified. Study objectives are to investigate: the demographic and the clinical characteristics of type 2 diabetes patients in Ontario, Canada over a time frame from Apr 1, 2002 to Sept 31, 2017. We also compare the demographics and clinical characteristics of T2DM patient populations from the cohorts to understand the impact T2DM definitions have on characterizing the disease. We identify 1,093,812 and 783,228 in the cohorts (Table 1) . In the sensitive and specific cohorts, the mean age of a patient with T2D is 64 to 65 years old and 52 to 54% are male, respectively. Roughly 56 to 64% of patients have a 1-year mean HbA1c of Disclosure R.L. Houlden: Advisory Panel; Novo Nordisk Canada Inc. Research Support; AstraZeneca. Speaker's Bureau; Abbott Diagnostics, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Canada Inc., Sanofi. S. Golden: Other Relationship; Novo Nordisk Canada Inc. W. Shi: Other Relationship; Novo Nordisk Canada Inc. A.A. Kukaswadia: Other Relationship; Novo Nordisk. A. Sharma: Other Relationship; Novo Nordisk Canada Inc. K. Quansah: Employee; Boehringer Ingelheim (Canada) Ltd., Novo Nordisk Canada Inc. A.R. Liu: Employee; Novo Nordisk A/S, Novo Nordisk Canada Inc.

Plasmonically induced transparency (PIT) effect in a metal–insulator–metal waveguide coupled to asymmetric three rectangle resonators and an appearance that one PIT peak fall while the other PIT peak rise are investigated numerically. PIT is widely studied duo to the performance on sensing, slow slight and nonlinear effects, which has great potential to be applied on optical communication system. To get a better insight of PIT effect in multi-rectangle resonators, herein, PIT peaks fluctuation is employed to numerically investigate its corresponding properties, effects and performance. By modify geometric parameters and filling dielectric, not only the off-to-on PIT optical response within single or double peaks can be realized, but also the fluctuation of peaks can be achieved as well. Additionally, our findings are well consistent with finite element simulation outcomes. These proposed structures also possess great potential in both communication and sensing applications.

Chemotherapy is one of the most important strategies in the treatment of cancer; however, chemoresistance restricts the effect of chemotherapy. Growing reports suggest that chloride channel-3 (ClC-3) is involved in regulating the sensitivity of multiple chemotherapeutic agents in the chemotherapy of various tumours, while its role in the chemotherapy of cholangiocarcinoma (CCA) is still poorly understood. Herein, we observed that ClC-3 was highly expressed in CCA chemoresistant tissues and CCA cisplatin-resistant cells QBC939/DDP, and the sensitivities of QBC939 and QBC939/DDP cells to cisplatin were all increased after inhibition of ClC-3. Further mechanism exploration revealed that ClC-3 knockdown reduced the level of autophagy. Furthermore, in both QBC939 and QBC939/DDP cells, the autophagy agonist rapamycin eliminated the increased cisplatin sensitivity of ClC-3 knockdown without affecting ClC-3 expression. Collectively, all the findings demonstrate that ClC-3 knockdown increases cisplatin-induced cell death in CCA cells though inhibiting autophagy, regardless of the occurrence of cisplatin resistance. In addition, our results also suggest that targeted inhibition of ClC-3 may be a potential strategy for chemosensitization in CCA chemotherapy.

Muscle-invasive bladder cancer (MIBC) is an aggressive disease requiring active management. Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is considered the standard treatment paradigm for MIBC patients, which could result in significant perioperative mortality and morbidity, as well as the significant alteration of the quality of life (QOL). Notably, multimodal bladder-preserving treatment strategies have been recommended for highly selected patients. Pathologic complete response (pCR) after NAC is a powerful prognostic indicator of survival for patients with MIBC. Clinical complete response (cCR) is then introduced as a complementary endpoint for pCR to assess disease status preoperatively. Bladder preservation strategy for patients who achieve cCR following NAC is emerging as a new treatment concept. However, the efficiency of the conservative strategy remains controversial. In this state-of-the-art review, we discuss the advantages and limitations of cCR and the feasibility and safety of bladder preservation strategy in highly selected MIBC patients who achieve cCR following NAC. We conclude that a conservative strategy can be considered a reasonable alternative to RC in carefully selected cCR MIBC patients, leading to acceptable oncological outcomes.

Background: With significant clinical effects, traditional Chinese medicine (TCM) has been attracting increasing interest of the world’s scientific community. However, TCM contains immense amounts of chemical components. It is a great challenge to objectively evaluate the correlation between the in vivo process and the therapeutic effect of TCM. The purpose of this systematic review was to summarize the recent investigation (from 2017 to 2019) on preclinical pharmacokinetics (PK) of TCM via liquid chromatography coupled with mass spectrometry (LC-MS/MS). Method: We reviewed the published articles regarding the PK of TCM by LC-MS/MS. In addition, we summarized information on PK parameter of bioactive components, single herb and traditional Chinese medicine prescriptions. Results: The vast majority of literature on preclinical PK of TCM uses single oral administration, the biological matrix is mostly rat plasma, and the main PK parameters include AUC, Cmax, Tmax and T1/2, etc. Conclusion: Although LC-MS/MS can be used for high-throughput analysis, the characterization of in vivo processes of TCM still has a long way. With the advantages of high sensitivity, high specificity and simple operation, the increasingly mature LC-MS/MS technology will play an important role in the PK study of TCM.

During a long-duration manned spaceflight mission, such as flying to Mars and beyond, all crew members will spend a long period in an independent spacecraft with closed-loop bioregenerative life-support systems. Saving resources and reducing medical risks, particularly in mental heath, are key technology gaps hampering human expedition into deep space. In the 1960s, several scientists proposed that an induced state of suppressed metabolism in humans, which mimics 'hibernation', could be an ideal solution to cope with many issues during spaceflight. In recent years, with the introduction of specific methods, it is becoming more feasible to induce an artificial hibernation-like state (synthetic torpor) in non-hibernating species. Natural torpor is a fascinating, yet enigmatic, physiological process in which metabolic rate (MR), body core temperature (Tb ) and behavioural activity are reduced to save energy during harsh seasonal conditions. It employs a complex central neural network to orchestrate a homeostatic state of hypometabolism, hypothermia and hypoactivity in response to environmental challenges. The anatomical and functional connections within the central nervous system (CNS) lie at the heart of controlling synthetic torpor. Although progress has been made, the precise mechanisms underlying the active regulation of the torpor-arousal transition, and their profound influence on neural function and behaviour, which are critical concerns for safe and reversible human torpor, remain poorly understood. In this review, we place particular emphasis on elaborating the central nervous mechanism orchestrating the torpor-arousal transition in both non-flying hibernating mammals and non-hibernating species, and aim to provide translational insights into long-duration manned spaceflight. In addition, identifying difficulties and challenges ahead will underscore important concerns in engineering synthetic torpor in humans. We believe that synthetic torpor may not be the only option for manned long-duration spaceflight, but it is the most achievable solution in the foreseeable future. Translating the available knowledge from natural torpor research will not only benefit manned spaceflight, but also many clinical settings attempting to manipulate energy metabolism and neurobehavioural functions.

Purpose Autologous bone grafts are the gold standard for treating bone defects. However, limited bone supply and morbidity at the donor site restrict its extensive use. Therefore, developing bone graft materials as an alternative to autologous grafts has gained considerable attention. Injectable hydrogels endowed with osteogenic potential have the ability to fill irregular bone defects using minimally invasive procedures and have thus been attracting researchers' attention. However, from a clinical perspective, most fabrication methods employed for the current injectable osteogenic hydrogels are difficult and inconvenient. In the current study, we fabricated an injectable osteogenic hydrogel using a simple and convenient strategy. Materials and methods Gelatin-methacryloyl (GelMA) pre-polymer was synthetized. Nano silicate (SN) and stromal cell-derived factor-1 alpha (SDF-1α) were introduced into the pre-polymer to achieve injectability, controlled release property, excellent osteogenic ability, and efficient stem cell homing. Results The GelMA-SN-SDF-1α demonstrated excellent injectability via a 17-G needle at room temperature. The loaded SDF-1α exhibited a long-term controlled release pattern and efficiently stimulated MSC migration and homing. The GelMA-SN-SDF-1α hydrogel amplified cell spreading, migration, osteogenic-related biomarker expression, and matrix mineralization. The GelMA-SN-SDF-1α hydrogel filled critical-sized calvaria defects in rats and demonstrated excellent bone regeneration ability, as assessed using micro-CT scanning and histomorphometric staining. Conclusion The GelMA-SN-SDF-1α hydrogel provides a simple and convenient strategy for the fabrication of injectable osteogenic graft materials.

Significance Identifying the conditions for complete metallization of diamond solely through mechanical strain is an important scientific objective and technological demonstration. Through quantum mechanical calculations, continuum mechanics simulations validated by experiments, and machine learning, we show here that reversible metallization can be achieved in diamond deformed below threshold elastic strain levels for failure or phase transformation. The general method outlined here for deep elastic strain engineering is also applicable to map the strain conditions for indirect-to-direct bandgap transitions. Our method and findings enable extreme alterations of semiconductor properties via strain engineering for possible applications in power electronics, optoelectronics, and quantum sensing., Experimental discovery of ultralarge elastic deformation in nanoscale diamond and machine learning of its electronic and phonon structures have created opportunities to address new scientific questions. Can diamond, with an ultrawide bandgap of 5.6 eV, be completely metallized, solely under mechanical strain without phonon instability, so that its electronic bandgap fully vanishes? Through first-principles calculations, finite-element simulations validated by experiments, and neural network learning, we show here that metallization/demetallization as well as indirect-to-direct bandgap transitions can be achieved reversibly in diamond below threshold strain levels for phonon instability. We identify the pathway to metallization within six-dimensional strain space for different sample geometries. We also explore phonon-instability conditions that promote phase transition to graphite. These findings offer opportunities for tailoring properties of diamond via strain engineering for electronic, photonic, and quantum applications.

PurposeTo address the gap of divergent conclusions on the impact of knowledge search (KS) on performance, this paper aims to discuss the nonlinear relationships between KS and reverse internationalization enterprise (RIE) performance, and the co-moderation of causation and effectuation (C&E) on KS–performance.Design/methodology/approachThe proposed theoretical model is developed by integrating the theory of knowledge-based view and decision rationality theory. The empirical study is based on survey data collected from 245 RIEs of the Yangtze River Delta and Pearl River Delta regions in China. Hierarchical multiple regression and the appropriate U-test method are used to test the hypotheses.FindingsEmpirical results suggest that both focused and multi-focus searches have inverted U-shaped effects on RIE performance. Furthermore, causation weakens the curvilinear effect between multi-focus search and RIE performance, whereas effectuation strengthens the curvilinear effect but weakens the inverted U-shaped relationship between focused search and RIE performance. Results also indicate that the integration of C&E positively moderates the relationship between focused or multi-focus searches and RIE performance.Originality/valueFindings reveal the nonlinear effects of focused and multi-focus searches on RIE performance and clarify the dispute over the mechanism of KS on performance by proposing the different moderating role of C&E. Moreover, this research provides deeper insight into contingency mechanisms between KS and performance by integrating the co-moderating role of C&E in RIEs.