Search

This is a case of a young woman who developed neurological and psychiatric symptoms 3 days after resection of an immature teratoma. She was diagnosed with anti-NMDA receptor encephalitis via positive serum antibody titres, which was later confirmed with cerebrospinal fluid antibody titres. Given her cancer diagnosis, she underwent treatment with bleomycin, etoposide and cisplatin chemotherapy in addition to 5 days of high-dose steroids (1 g of intravenous methylprednisolone) for the encephalitis. This treatment regimen led to significant clinical improvement 3 weeks after completion of one cycle of chemotherapy.

Magnesium hydride (MgH2) is one of the most promising hydrogen storage materials for practical application due to its favorable reversibility, low cost and environmental benign; however, it suffers from high dehydrogenation temperature and slow sorption kinetics. Exploring proper catalysts with high and sustainable activity is extremely desired for substantially improving the hydrogen storage properties of MgH2. In this work, a composite catalyst with high-loading of ultrafine Ni nanoparticles (NPs) uniformly dispersed on porous hollow carbon nanospheres is developed, which shows superior catalytic activity towards the de-/hydrogenation of MgH2. With an addition of 5 wt% of the composite, which contains 90 wt% Ni NPs, the onset and peak dehydrogenation temperatures of MgH2 are lowered to 190 and 242 °C, respectively. 6.2 wt% H2 is rapidly released within 30 min at 250 °C. The amount of H2 that the dehydrogenation product can absorb at a low temperature of 150 °C in only 250 s is very close to the initial dehydrogenation value. A dehydrogenation capacity of 6.4 wt% remains after 50 cycles at a moderate cyclic regime, corresponding to a capacity retention of 94.1%. The Ni NPs are highly active, reacting with MgH2 and forming nanosized Mg2Ni/Mg2NiH4. They act as catalysts during hydrogen sorption cycling, and maintain a high dispersibility with the help of the dispersive role of the carbon substrate, leading to sustainably catalytic activity. The present work provides new insight into designing stable and highly active catalysts for promoting the (de)hydrogenation kinetics of MgH2.

Highly durable and stretchable ionic conductors are indispensable components for flexible electronics. However, fabricating such ionic conductors that are also non-toxic and biodegradable remains a...

Sinomenine (SIN) is commonly used as part of rheumatoid arthritis (RA) therapy in China, but there is still no published evidence of the efficacy of SIN monotherapy. This work investigates the efficacy and safety of SIN in treating RA patients and analyzes the correlation between ornithine level and the alleviation of disease activity in RA patients. In this 24 week, randomized, placebo-controlled, double-blind clinical trial, people with mild to moderate RA were randomly assigned (1:1:1, stratified by hospital) to receive SIN (120 mg, twice daily), methotrexate (MTX) (10 mg per week), or SIN + MTX therapy. The primary outcome was the proportion of patients who achieved a 50% improvement in the American College of Rheumatology (ACR) criteria at week 24 and who showed improvement according to the clinical disease activity index (CDAI). In this prospective subgroup analysis, we also assessed whether the 24 week alterations of disease activity in the treatment group were significantly correlated to the levels of blood ornithine. Of the 135 enrolled participants, 38, 39, and 36 patients were treated with SIN, MTX, and SIN + MTX, respectively. In the SIN-treated group, 52.63% of patients achieved ACR50 after 24 weeks of treatment, which was comparable to the results in the MTX-treated and SIN + MTX-treated groups. Hepatic and gastrointestinal disorders were the main adverse events; however, the ratio of patients suffering from hepatic disorder in the SIN group (1/38) was much lower than that in the MTX (10/39) and SIN + MTX (8/36) groups. A total of 221 serum samples were collected at the four follow-up time points in the three treatments, and the levels of ornithine, citrulline, and arginine were obtained through ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). The serum ornithine level decreased after the 24 week treatment along with a decrease in disease activity, and may reflect therapeutic responses with a sensitivity value of 80%. In conclusion, SIN revealed a comparable efficacy to MTX for treating RA patients, but with fewer side effects. In addition, the serum ornithine level was found for the first time to have a close correlation with the alleviation of RA, which shows the value of this measure as an assessment indicator of drugs in treating RA.

The rapid and sensitive detection of 2,6-pyridinedicarboxylic acid (DPA), one of the main biomarkers of Bacillus anthracis, is of great significance for the screening and diagnosing of anthrax. Herein, a ratiometric fluorescent nanoprobe based on zeolite imidazolate framework-8 (ZIF-8)@AuNCs-Tb was constructed by embedding both gold nanoclusters (AuNCs) and terbium ions (Tb3+) into ZIF-8 for high-resolution visual detection of DPA. Due to the aggregation induced emission enhancement (AIE) effect, AuNCs embedded in ZIF-8 emit a strong orange fluorescence. When Tb3+ is coordinated with DPA added to the nanoprobe, it will emit a strong green fluorescence owing to the antenna effect. The results reveal that ZIF-8@AuNCs-Tb nanoprobe can detect DPA effectively with a good linear relationship in the range of 40–200 and 200–1000 μmol/L, the limit of detection (LOD) is estimated at 1.8 μmol/L (3σ/k). The proposed nanoprobe shows a remarkable selectivity for DPA and is quite easy to realize visualization based on the fluorescent color changing from orange to green, which has potential application in clinical diagnosis. The feasibility of this method was verified by standard addition recovery experiments simulating the release of DPA from spores.

There are many areas in the world where the ground water has been contaminated by arsenic. MnO2 is one of the most cheap materials which can both adsorb arsenic and oxide arsenite [As(III)]...

We investigate the role of wildfire smoke on ozone photochemical production (P(O3)) and atmospheric boundary layer (ABL) dynamics in California's Central Valley during June–September from 2016 to 2020. Wildfire events are identified by the Hazard Mapping System (HMS) and the Hybrid Single Particle Lagrangian Integrated Trajectory Model (HYSPLIT). Air quality and meteorological data are analyzed from 10 monitoring sites operated by the California Air Resources Board (CARB) across the Central Valley. On average, wildfires were found to influence air quality in the Central Valley on about 20 % of the total summer days of the study. During wildfire-influenced periods, maximum daily 8 h averaged (MDA8) O3 was enhanced by about 5.5 ppb or 10 % of the median MDA8 (once corrected for the slightly warmer temperatures) over the entire valley. Overall, nearly half of the total exceedances of the National Ambient Air Quality Standards (NAAQS) where MDA8 O3 > 70 ppb occur under the influence of wildfires, and approximately 10 % of those were in exceedance by 5 ppb or less indicating circumstances that would have been in compliance with the NAAQS were it not for wildfire emissions. The photochemical ozone production rate calculated from the modified Leighton relationship was also found to be higher by 50 % on average compared with non-fire periods despite the average diminution of j(NO2) by ∼ 7 % due to the shading effect of the wildfire smoke plumes. Surface heat flux measurements from two AmeriFlux sites in the northern San Joaquin Valley show midday surface buoyancy fluxes decrease by 30 % on average when influenced by wildfire smoke. Similarly, afternoon peak ABL heights measured from a radio acoustic sounding system (RASS) located in Visalia in the southern San Joaquin Valley were found to decrease on average by 80 m (∼ 15 %) with a concomitant reduction of downwelling shortwave radiation of 54 Wm−2, consistent with past observations of the dependence of boundary layer heights on insolation.

High applied thermal-stability and superior structural property for activated carbon adsorbent are extremely promising, which also is the determining short slab in volatile organic compounds (VOCs) adsorption applications. Herein, we develop the outstanding engineering carbon adsorbents from waste shaddock peel which affords greatly-enhanced thermal-stability and super structural property (SLang=4962.6 m2·g−1, Vmicro=1.67 cm3·g−1). Such character endows the obtained adsorbent with ultrahigh adsorption capture performance of VOCs specific to benzene (16.58 mmol·g−1) and toluene (15.50 mmol·g−1), far beyond traditional zeolite and activated carbon even MOFs materials. The structural expression characters were accurately correlated with excellent adsorption efficiency of VOCs by studying synthetic factor-controlling comparative samples. Ulteriorly, adsorption selectivity prediction at different relative humidity was demonstrated through DIH (difference of the isosteric heats), exceedingly highlighting great superiority (nearly sixfold) in selective adsorption of toluene compared to volatile benzene. Our findings provide the possibility for practical industrial application and fabrication of waste biomass-derived outstanding biochar adsorbent in the environmental treatment of threatening VOCs pollutants.

Pseudourine (Ψ) is the most abundant cellular RNA modification, present in tRNA, rRNA, snRNA, mRNA, long noncoding RNA (lncRNA), and others. Ψ sites and fractions are dynamically regulated in stress response and across development stages. Although high throughput Ψ sequencing methods based on N-Cyclohexyl-N'-(2-morpholinoethyl)carbodiimide (CMC) reaction are available for Ψ detection transcriptome-wide, a simple method for the analysis of specific, targeted Ψ sites and their fraction quantitation is needed to better investigate Ψ function. Here, we describe an RT-PCR and gel electrophoresis based method that can sensitively and quantitatively assess Ψ at single-nucleotide resolution in mRNA/lncRNA, termed CMC-RT and ligation assisted PCR analysis of Ψ modification (CLAP). The principle of the CMC-method is the reverse transcription stop induced by the CMC-Ψ adduct. In CLAP, CMC reaction is first carried out with the RNA sample. Reverse transcription using a non-processive RT produces two cDNA products for each RNA transcript, one with the 3' end at the Ψ site, the other read-through product from the unmodified RNA. Using splint oligonucleotide assisted site-specific ligation, these two cDNA products are then visualized on a gel as two distinct PCR products in the same lane corresponding to the Ψ-modified and unmodified target site. CLAP validates Ψ sites identified by high throughput sequencing, quantifies Ψ levels in mRNA and lncRNA, and enables convenient and rapid investigation on the function and mechanism of the Ψ modification.

Atom-intercalated transition metal disulfides (TMDs) have attached much attention mainly due to their highly improved conductivity. But it is few reported that the atom intercalation can enable the TMDs have unexpected catalytic properties, caused by the unit-cell deformation in them. In this work, a type of V0.25-intercalated VS2 (V5S8) nanoflakes was designed via a direct vulcanization method combining Kirkendall heat diffusion effect, and used as the promotor for lithium-sulfur batteries (LSBs). The V5S8 possesses a NiAs crystal structure, in which V atoms occupy the interlayer spacing between VS2 monolayers, which will unavoidably cause the unit-cell deformation. As expected, the CNF@V5S8/S cathodes show a specific capacity of 1260 mAh g−1 at 0.2 C, and can keep 73.65% of the capacity with charge/discharge rate increasing 10 times; while the CNF@VS2/S ones can only retain 54.0% of the initial capacity. Moreover, the CNF@V5S8/S cathodes show an ultralow decay rate of only 0.0312% per cycle for 1500 cycles at 5 C. Furthermore, the catalysis effect of V5S8 on the conversion of lithium polysulfide (Li2Sn, n = 1, 2, 4, 6 and 8) and S8 clusters were systematically discusses. Besides, the V5S8 can further enable LSBs achieve a high areal capacity (8.2 mAh cm−2 with sulfur loading of 7.8 mg cm−2) and a high dynamic flexible stability at bending angle between 0 and 180 °.

Presently Si-based field-effect transistors (FETs) are approaching their physical limit, and further scaling their gate length down to the sub-10 nm region is becoming extremely difficult. Benefitting from the atomic-scale thickness and dangling-bond-free flat surface, two-dimensional semiconductors (2DSCs) have good electrostatics and carrier transportability. The FETs based on the 2DSC channel have the potential to scale the FETs’ gate length down to the sub-10 nm region while avoiding apparent degradation of the device performance. In this review, we introduce the recent experimental and ab initio quantum transport simulation progress in the 2D FETs with a gate length less than 10 nm. Remarkably, in the extremely optimistic condition, many 2D FETs (i.e phosphorene, silicane, arsenene, tellurene, WSe2, InSe, Bi2O2Se, GeSe, etc.) show excellent device performance for the high performance and/or low power applications and indeed can extend Moore’s law down to 1 ∼ 2-nm gate length in terms of the ab initio quantum transport simulation. The sub-10 nm 2D tunneling FETs are predicted to generally have smaller energy-delay products compared with the 2D metal–oxide–semiconductor FETs and appear more competitive for the low power application. The carrier effective mass plays a key role in determining the device performance. Via negative capacitance techniques, the device performance can be further improved. Finally, we outline the challenges and outlook on the future development directions in the sub-10 nm 2D FETs.

Background. Colorectal cancer (CRC) is the third most common tumor worldwide. Aberrant N6-methyladenosine (m6A) modification can influence the progress of the CRC. Additionally, long noncoding RNA (lncRNA) plays a critical role in CRC and has a close relationship with m6A modification. However, the prognostic potential of m6A-related lncRNAs in CRC patients still remains to be clarified. Methods. We use “limma” R package, “glmnet” R package, and “survival” R package to screen m6A-related-lncRNAs with prognostic potential. Then, we comprehensively analysed and integrated the related lncRNAs in different TNM stages from TCGA database using the LASSO Cox regression. Meanwhile, the relationship between functional enrichment of m6A-related lncRNAs and immune microenvironment in CRC was also investigated using the TCGA database. A prognostic model was constructed and validated to determine the association between m6A-related lncRNAs in different TNM stages and the prognosis of CRC. Result. We demonstrated that three related m6A lncRNAs in different TNM stages were associated with the prognosis of CRC patients. Patients from the TCGA database were classified into the low-risk and the high-risk groups based on the expression of these lncRNAs. The patients in the low-risk group had longer overall survival than the patients in the high-risk group ( P < 0.001 ). We further constructed and validated a prognostic nomogram based on these genes with a C-index of 0.80. The receiver operating characteristic curves confirmed the predictive capacity of the model. Meanwhile, we also found that the low-risk group has the correlation with the dendritic cell (DC). Finally, we discovered the relationship between the m6A regulators and the three lncRNAs. Conclusion. The prognostic model based on three m6A-related lncRNAs exhibits superior predictive performance, providing a novel prognostic model for the clinical evaluation of CRC patients.

Pickering emulsions stabilized by solid particles have gained much attention, which afford high stability, low toxicity, controllable rheological properties and stimuli-responsive behavior compared to the traditional emulsions emulsified by surfactants. Those particles, as the core parts of the emulsion systems, play an important role in the fabrication and application of Pickering emulsion systems, making them attractive in petroleum fields. In this review, the influence of various particles on the stability and properties of Pickering emulsion systems as well as recent researches associated with the stimuli-responsibility of Pickering emulsion systems are introduced. Specifically, the design of functional particles and Pickering emulsion systems with super stabilities and controllable rheological properties are listed. Furthermore, some petroleum application of Pickering emulsion systems for enhanced oil recovery and spilled oil collection as well as the application as soft templates to fabricate oil-absorbing material and as three-phase microreactors that most likely for petroleum application are discussed, and the issues hindering the actual application of Pickering emulsion systems are also evaluated. This review charts a way for Pickering emulsion studies that could lead to a valid petroleum application through design of the particles served as the enhancers of Pickering emulsion stability for purpose of tailoring chemical flooding.

The uranyl with two U=O double bonds is a well-known and predominant form of uranium in the environment, but the carbon-based analog with two U=C double bonds has rarely been synthesized. Here, we ...

The present study was carried out to evaluate the effect of dietary supplemental vitamin D3 on fibroblast growth factor 23 (FGF23) signals as well as phosphorus homeostasis and metabolism in laying hens. Fourteen 40-week-old Hy-Line Brown layers were randomly assigned into 2 treatments:1) vitamin D3 restriction group (n = 7) fed 0 IU/kg vitamin D3 diet, and 2) regular vitamin D3 group (n = 7) fed 1,600 IU/kg vitamin D3 diet. The study lasted for 21 d. Serum parameters, phosphorus and calcium excretion status, and tissue expressions of type II sodium-phosphate co-transporters (NPt2), FGF23 signals and vitamin D3 metabolic regulators were determined. Hens fed the vitamin D3 restricted diet had decreased serum phosphorus levels (by 31.3%, P = 0.028) when compared to those fed regular vitamin D3 diet. In response to the decreased serum phosphorus, the vitamin D3 restricted laying hens exhibited: 1) suppressed kidney expressions of 25-hydroxyvitamin D 1-α-hydroxylase (CYP27B1, by 52.8%, P = 0.036) and 1,25-dihydroxyvitamin D 24-hydroxylase (CYP24A1, by 99.4%, P = 0.032); 2) suppressed serum levels of FGF23 (by 14.6%, P = 0.048) and increased serum alkaline phosphatase level (by 414.1%, P = 0.012); 3) decreased calvaria mRNA expressions of fibroblast growth factor receptors (FGFR1, by 85.2%, P = 0.003, FGFR2, by 89.4%, P = 0.014, FGFR3, by 88.8%, P = 0.017, FGFR4, by 89.6%, P = 0.030); 4) decreased kidney mRNA expressions of FGFR1 (by 65.5%, P = 0.021), FGFR4 (by 66.0%, P = 0.050) and KLOTHO (by 68.8%, P = 0.038); 5) decreased kidney protein expression of type 2a sodium-phosphorus co-transporters (by 54.3%, P = 0.039); and 6) increased percent excreta calcium (by 26.9%, P = 0.002). In conclusion, the deprivation of dietary vitamin D3 decreased FGF23 signals in laying hens by reducing serum FGF23 level and suppressing calvaria and kidney mRNA expressions of FGF23 receptors.

Tuning white-light emission via free radicals is still a challenge in molecular-based functional materials. Herein, a new photoactive Zn2+ oxalate-based chain containing a polypyridine ligand was designed and synthesized with remarkably bifunctional photochromism and photo-actuated greenish white-light emission after UV, sunlight or Xe lamp light irradiation at room temperature. The photo-actuated coloration process was induced by the photogeneration of stable radicals originated from intermolecular electron transfers from oxalate components to the protonated polypyridine units, as demonstrated by UV-vis, IR, electron spin resonance and X-ray photoelectron spectra and magnetic measurements. Importantly, the on/off greenish white light emission (WLE) could be reversibly switched by generation and elimination of radicals via light irradiation and heat treatment, providing a feasible strategy for designing photoswitchable light emission diodes materials.

This study proposes a new method using the combination of flocculation and prefabricated horizontal drain (PHD) assisted with vacuum pressure for rapid dewatering of high-water-content dredged slurry. First, to demonstrate the superiority of using PHD over the more commonly used prefabricated vertical drain (PVD), experiments were conducted to compare the dewatering performance between the PHD and the PVD. Then six model tests with the proposed dewatering method were performed with various contents of flocculant (anionic polyacrylamide (APAM)) to investigate the effect of APAM content on the dewatering process and soil properties (i.e. undrained shear strength, permeability and compressibility). Furthermore, particle size distributions of the slurry before and after model tests were measured to analyze the dewatering behavior and changes in material properties. Finally, particle loss during vacuum consolidation for various APAM contents were compared to study the flocculation effect on clogging problem. Results indicate that the proposed method can prevent significant bending deformation of the drain board and mitigate clogging of the drain filter and, thus, can significantly accelerate the dewatering process of high-water-content dredged slurry.

Dietary fiber is named as “the 7th nutrient” for humans, which is beneficial to improve intestinal health and prevent metabolic disease of the host. Mechanisms of dietary fiber administration on improved host health are mediated by short chain fatty acids (SCFA), which are reported to activate G protein-coupled receptors (GPR) and suppress activity of histone deacetylase (HDAC) to down-regulate expression of nuclear factor-к-gene binding (NF-кB) signaling. Arabinoxylan is fermented by gut microbiota to produce SCFA and improved microbial community composition, intestinal barrier functions and host health. Interestingly, the latest publications have observed that ferulic acid combined with the arabinose in arabinoxylans from various cereal grains can be released through gut microbial fermentation. Ferulic acid can improve antioxidase activity and decrease reactive oxygen species (ROS) concentration by activating the signaling pathway of Kelch-like ECH-associated protein-1 and nuclear factor E2-related factor-2 (Keap1-Nrf2). However, the role of ferulic acid in cooperation with SCFA produced from microbial fermentation of cereal-derived arabinoxylan to regulate the intestinal health and host metabolisms, has been widely unclear. This review summarizes the potential mechanisms of ferulic acid from microbial fermentation of cereal-derived arabinoxylans on immunological functions and physiological metabolisms of the host. The evidence presented in the review indicates that dietary supplementation with cereal-derived arabinoxylans improves antioxidant capacity of intestinal epithelial cells due to the production of ferulic acid and SCFA from microbial fermentation. Ferulic acid can cooperate with SCFA to regulate intestinal integrity and immunological functions of the host. Peroxisome proliferator activated-receptor γ (PPARγ) may play an important role in integrating ferulic acid and SCFA to regulate host health and metabolism.

Adding hydrogen to the fuel can change the combustion characteristics and greatly improve the pollutants emission for the gas turbine. The numerical method was adopted to study the combustion process in a counter-flow combustor of a 100 kW micro gas turbine using methane doped by hydrogen and various distribution schemes of air flow. The combustion characteristics and pollutant emissions were explored to ascertain the influence of air distribution based on solving the validated models. It was shown that as the amount of premixed air increased in the swirling gas, the range of the recirculation region became larger and the range of the high-temperature zone in the combustion chamber gradually enlarged. When the amount of premixed air was 30%, the outlet temperature distribution of the combustor was excellent and the average temperature was 1172 K. Moreover, the concentration of NO X gradually increased and reached a maximum value of 23.46 ppm (@15% O 2 ) as the premixed air increased in the range of the ratio less than 40%. It was reduced to 0.717 ppm (@15% O 2 ) when the amount of premixed air increased to 50%. These findings may support the running of the micro gas turbine using the hybrid fuel of hydrogen and methane.

Microfluidics is characterized by the manipulation of fluids in submillimeter channels and has great application potential in encapsulation. To further extend the application of microfluidics in food industries, a 3D printed microfluidic device is used to encapsulate vitamin A and improve its stability. Two natural macromolecules, sodium alginate and gelatin, are added to water as the continuous phase to generate monodisperse emulsion. Under different flow rate ratios, the diameter of droplets decreases with the increase of continuous flow rate. However, at the same flow rate ratio, varying the dispersed and continuous flow rates does not significantly change the diameter and size distribution of emulsion collected. The prepared O/W (oil/water) single emulsion can form microgel particles and avoid degradation of vitamin A by simulated gastric acid; the encapsulated vitamin A will not be released until particles reach simulated intestinal tract. In the simulated digestion in vitro, no vitamin A is released for 2 h in the acidic environment; under an alkaline or neutral environment such as those in intestinal fluids, vitamin A can be released from the microgel particles within 2.5 h. Using the presented approach, emulsions encapsulating vitamin A have been prepared and can potentially be applied to encapsulate other oil-soluble substances in the food industry.

Dividing-wall columns (DWCs) are widely used in the separation of ternary mixtures, but rarely seen in the separation of petroleum fractions. This work develops two novel and energy-efficient designs of lubricant-type vacuum distillation process (LVDP) for the separation of hydroisomerization fractions (HIF) of a hydrocracking tail oil (HTO). First, the HTO hydroisomerization reaction is investigated in an experimental fixed-bed reactor to achieve the optimum liquid HIF by analyzing the impact of the operating conditions. A LVDP used for HIF separation is proposed and optimized. Subsequently, two thermal coupling intensified technologies, including side-stream (SC) and dividing-wall column (DWC), are combined with the LVDP to develop side-stream vacuum distillation process (SC-LVDP) and dividing-wall column vacuum distillation process (DWC-LVDP). The performance of LVDP, SC-LVDP, and DWC-LVDP are evaluated in terms of energy consumption, capital cost, total annual cost, product yields, and stripping steam consumption. The results demonstrates that the intensified processes, SC-LVDP and DWC-LVDP significantly decreases the energy consumption and capital cost compared with LVDP. DWC-LVDP further decreases in capital cost due to the removal of the side stripper and narrows the overlap between the third lube oils and fourth lube oils. This study attempts to combine DWC structure into the separation of petroleum fractions, and the proposed approach and the results presented provide an incentive for the industrial implementation of high-quality utilization of HTO through intensified LVDP.

Electrocatalysts with atomically dispersed metal moieties are of importance in enhancing electrocatalysis for a specific reaction including oxygen reduction. However, it is still challenging to modulate the coordination structure of metal atoms with heteroatoms on carbon supports. Herein, an innovative and facile bridging strategy to regulate the coordination structure of cobalt with nitrogen atoms on reduced graphene oxide (rGO) sheets was developed by the interfacial complexation of amino-rich folic acid with cobalt ions on graphene oxide sheets and the subsequent thermal treatment. Typically, the actual coordination interaction between cobalt and nitrogen species was revealed by using X-ray absorption spectroscopy (XAS), exhibiting the Co-N4 coordination structure well-dispersed on reduced graphene oxide. Such unique structure enables the efficient oxygen reduction and evolution reactions via the favorable adsorption and desorption of intermediates. With the enhanced bifunctional electrocatalytic activities, the fabricated Zn-air battery exhibited the excellent performance with large power density of 319.8 mW cm−2 and good long-term stability (over 300 h). This work establishes the synthesis strategy for bridging metal atom with heteroatom on graphene sheets to enhance the bifunctional electrocatalysis toward Zn-air batteries.

Objective: Excessive lipid accumulation in adipocytes results in prevalence of obesity and metabolic syndrome. Curcumin (CUR), a naturally phenolic active ingredient, has been shown to have lipid-lowering effects. However, its underlying mechanisms have remained largely unknown. Therefore, the study aims to determine the effect of CUR on cellular lipid accumulation in porcine subcutaneous preadipocytes (PSPA) and to clarify novel mechanisms.Methods: The PSPA were cultured and treated with or without CUR. Both cell counting Kit-8 and lactate dehydrogenase release assays were used to examine cytotoxicity. Intracellular lipid contents were measured by oil-red-o staining extraction and triglyceride quantification. Apoptosis was determined by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling assay. Adipogenic and apoptosis genes were analyzed by quantitative polymerase chain reaction and Western blot.Results: The CUR dose-dependently reduced the proliferation and lipid accumulation of PSPA. Noncytotoxic doses of CUR (10 to 20 μM) significantly inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and expression of adipogenic genes peroxisome proliferation-activity receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α, sterol regulatory element-binding protein-1c, adipocyte protein-2, glucose transporter-4 as well as key lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase, while ERK1/2 activation significantly reversed CUR-reduced lipid accumulation by increasing PPAR-γ. Furthermore, compared with differentiation induced media treated cells, higher dose of CUR (30 μM) significantly decreased the expression of AKT and B-cell lymphoma-2 (BCL2), while increased the expression of BCL-2-associated X (BAX) and the BAX/BCL-2 expression ratio, suggesting triggered apoptosis by inactivating AKT and increasing BAX/BCL-2 ratio and Caspase-3 expression. Moreover, AKT activation significantly rescued CUR inhibiting lipid accumulation via repressing apoptosis.Conclusion: These results demonstrate that CUR is capable of suppressing differentiation by inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis via decreasing AKT and subsequently increasing BAX/BCL-2 ratio and Caspase-3, suggesting that CUR provides an important method for the reduction of porcine body fat, as well as the prevention and treatment of human obesity.

This work produced a MgAl-layered double hydroxide by hydrothermal treatment of a plasma electrolytic oxidation (PEO) coating on magnesium alloy AZ31 in an phosphate electrolyte, followed by an ion-exchange reaction in 0.1 M phosphate solution. The coated specimens were scratched. Characterization, including utilization of the localized technique SIET, measured the pH and pMg distributions and optical morphologies around the artificial defects during immersion in 0.05 M NaCl solution. In contrast with phosphate loaded PEO/LDHs, a stronger alkalinization area (with pH 11.4∼12.3) appeared in the passive PEO specimens. Due to formation of insoluble Mg(OH)2 products, the pMg map showed depletion of Mg2+ in this high pH area. Combined with optical morphologies and SEM images, the better self-healing ability toward defects for phosphate loaded PEO/LDHs was confirmed.

Monovalent cation perm-selective membrane (MCPMs) allow fast and selective transport of monovalent cations, and they are promisingly required for extraction of special ions, such as lithium extraction, acid recovery and sea salt production. Herein, we report a novel strategy to design the critical functional layers of MCPMs with both space charge repulsion and cross-linked dense screenability. The in-situ deposition polymerization of pyrrole was carried out on the surface of sulfonated polyphenyl sulfone (SPPSU) substrate membrane followed by cross-linking quaternization of the polypyrrole (PPy) layer with diiodinated functional molecules, thus, the membrane obtained more excellent selective permeability and stable transport properties of monovalent cations. It confirms that the designed PPy layers with charged surface and cross-linking structure improved the hydrophilicity, facilitated cation transport and increased ion flux. Meanwhile, for the dense PPy layer, the charged cross-linked structure endowed the functional layer with the synergistic characteristics of Donnan exclusion and pore size sieving for positively charged ions, which improved the monovalent cation perm-selectivity of the membranes. At a constant current density of 5.1 mA/cm2, the optimal membrane exhibited superior perm-selectivity ( P Mg Na = 2.07 ) and monovalent cation flux (JNa+ = 2.80 × 10 −8 (mol cm−2 s−1)) during electrodialysis.

Though membrane distillation (MD) has gained more and more attention in the field of desalination, the wetting phenomenon was still a non-negligible problem. In this work, a method combined dip-coating and UV in situ polymerization for preparing hydrophobic/hydrophilic perfluoropolyether (PFPE)/polyvinylidene fluoride composite membranes. This composite membrane consisted of a top thin hydrophobic coating layer and hydrophilic substrate membrane. In terms of anti-wetting properties, contact angle and liquid entry pressure of all composite membranes (except for those based on 0.45 μm) exceeded 160o and 0.3 MPa, respectively. In particular, the desalination performance was tested in vacuum membrane distillation tests by feeding 3.5% (mass) saline solution (NaCl) at 60 oC. The composite membranes with larger support pore size and lower PFPE content had higher membrane distillation flux. And for stability tests (testing the 0.22 μm membrane coated by 5% (mass) PFPE), the highest MD flux 29.08 kg·m–2·h–1 and stable salt rejection (over 99.99%) during the period. Except that, the effects of coating material concentration and pore sizes of substrate membrane were also investigated for surface morphology and topography, porosity, mechanical strength and pore size characteristics. This work provided a simple and effective alternative to prepare excellent hydrophobic composite membranes for MD applications.

Background: In this study, Near-field electrospinning (NFES) technique used with a cylindrical collector to fabricate a large area permanent piezoelectric micro and nanofibers by a prepared solution. NFES requires a small electric field to fabricate fibers. Objective: The objective of this paper to investigate silver nanoparticle (Ag-NP)/ Polyvinylidene fluoride (PVDF) composite as the best piezoelectric material with improved properties to produced tremendously flexible and sensitive piezoelectric material with pertinent conductance. Method: In this paper we used controllable electrospinning technique based on Near-field electrospinning (NFES)The process parameter for Ag-NP/PVDF composite electrospun fiber based on pure PVDF fiber. A PVDF solution concentration of 18 wt.% and 6 wt.% silver nitrate which is relative to the weight of PVDF wt.% with 1058 µS conductivity fibers have been directly written on a rotating cylindrical collector for aligned fiber PVDF/Ag-NP fibers are patterned on fabricated copper (Cu) interdigitated electrodes were implemented on a thin flexible polyethylene terephthalate (PET) substrate and Polydimethylsiloxane (PDMS) used as a package to enhance the durability of the PVDF/ Ag-NP device. Results: A notable effect on the piezoelectric response has been observed after Ag-NP addition confirmed by XRD characterization and tapping test of Ag-NP/PVDF composite fiber. The morphology of the PVDF/Ag-NP fibers and measure diameter by scanning electron microscopy (SEM) and Optical micrograph (OM), of fiber. Finally, The result shows that diameter of PVDF/Ag-NP fibers up to ~7 μm. The. High diffraction peak at 2θ = 20.5˚ was investigated by X-ray diffraction (XRD) in the piezoelectric crystal β-phase structure. While the electromechanical conversion is found enhance from ~0.1 V to ~1 V by the addition of silver nanoparticles (Ag-NPs) in the PVDF solution. Conclusion: In conclusion, we can say that confirmed and validated the addition of Ag-NP in PVDF could enhance the piezoelectric property by using NFES technique with improved crystalline phase content can be useful for a wide range of power and sensing applications like biomedical devices and energy harvesting, among others.

Green and economical CO2 utilization is significant for CO2 emission reduction and energy development. Here, the 1D Mo2C nanowires with dominant (101) crystal surfaces were modified by the deposition of atomic functional components Rh and K. While unmodified β­Mo2C could only convert CO2 to methanol, the designed catalyst of K0.2Rh0.2/β-Mo2C exhibited up to 72.1% of ethanol selectivity at 150 °C. It was observed that the atomically dispersed Rh could form the bifunctional active centres with the active carrier β­Mo2C with the synergistic effects to achieve highly specific controlled C–C coupling. By promoting the CO2 adsorption and activation, the introduction of an alkali metal (K) mainly regulated the balanced performance of the two active centres, which in turn improved the hydrogenation selectivity. Overall, the controlled modification of β­Mo2C provides a new design strategy for the highly efficient, low-temperature hydrogenation of CO2 to ethanol with single-atom catalysts, which provides an excellent example for the rational design of the complex catalysts.

Acute kidney injury (AKI) is a common syndrome that has a significant impact on prognosis in various clinical settings. To evaluate whether new evidence supports changing the current definition/classification/staging systems for AKI suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline, the Taiwan AKI-TASK Force, composed of 64 experts in various disciplines, systematically reviewed the literature and proposed recommendations about the current nomenclature and diagnostic criteria for AKI. The Taiwan Acute Kidney Injury (TW-AKI) Consensus 2020 was established following the principles of evidence-based medicine to investigate topics covered in AKI guidelines. The Taiwan AKI-TASK Force determined that patients with AKI have a higher risk of developing chronic kidney disease, end-stage renal disease, and death. After a comprehensive review, the TASK Force recommended using novel biomarkers, imaging examinations, renal biopsy, and body fluid assessment in the diagnosis of AKI. Clinical issues with regards to the definitions of baseline serum creatinine (sCr) level and renal recovery, as well as the use of biomarkers to predict renal recovery are also discussed in this consensus. Although the present classification systems using sCr and urine output for the diagnosis of AKI are not perfect, there is not enough evidence to change the current criteria in clinical practice. Future research should investigate and clarify the roles of the aforementioned tools in clinical practice for AKI.

Objective The mainstay of treatment for patients with malignant pleural disease is fluid drainage and systemic therapy. A tumor-specific oncolytic virus or T-cell–activating interleukin-2 immunotherapy may provide an opportunity for local control. We previously developed a vaccinia virus–expressing interleukin-2, an oncolytic virus that mediated tumor regression in preclinical peritoneal tumor models with expansion of tumor-infiltrating lymphocytes. We evaluated the antitumor efficacy and immune modulatory effects of vaccinia virus–expressing interleukin-2 in malignant pleural disease. Methods A murine model of malignant pleural disease was established with percutaneous intrapleural deposition of the Lewis lung carcinoma cell line and monitored with bioluminescent imaging. After intrapleural or systemic administration of vaccinia viruses (vaccinia virus yellow fluorescent protein control, vaccinia virus–expressing interleukin-2), systemic anti–programmed cell death-1 antibody, or combination therapy (vaccinia virus–expressing interleukin-2 and anti–programmed cell death-1), tumor mass, immune cell infiltration, T-cell receptor diversity, and survival were assessed. Results Intrapleural vaccinia virus resulted in significant tumor regression compared with phosphate-buffered saline control (P Conclusions Intrapleural vaccinia virus–expressing interleukin-2 reduced tumor burden and enhanced survival in a murine malignant pleural disease model. Increased CD8+ tumor-infiltrating lymphocytes and αβ T-cell receptor diversity are associated with enhanced response. Clinical trials will enable assessment of intrapleural vaccinia virus–expressing interleukin-2 therapy in patients with malignant pleural disease.

Utilizing catalysts to accelerate the redox kinetics of lithium polysulfides (LiPSs) is a promising strategy to alleviate the shuttle effect of lithium−sulfur (Li−S) batteries. Nevertheless, most of the reported catalysts are only effective for LiPSs reduction, resulting in the devitalization of catalysts over extended cycles as a consequence of the continuous accumulation of Li2S passivation layer. The situation gets even worse when employing mono-directional catalyst with poor electron conductivity because the charge transfer for the decomposition of solid Li2S is severely hampered. Herein, a high-conductive and dual-directional catalyst Co3C decorated on porous nitrogen-doped graphene-like structure and carbon nanotube (Co3C@PNGr-CNT) is fabricated as sulfur host, which not only promotes the precipitation of Li2S from LiPSs during discharge but also facilitates the decomposition of Li2S during subsequent charge, as evidenced by the reduced activation energies for both reduction and oxidation processes. Furthermore, the long-term catalytic stability of Co3C is corroborated by the reversible evolution of Co–C bond length over extended cycles as observed from X-ray absorption fine structure results. As a consequence, the fabricated Co3C@PNGr-CNT/S cathode delivers a low capacity decay of 0.043% per cycle over 1000 cycles at 2 C. Even at high sulfur loading (15.6 mg cm−2) and low electrolyte/sulfur (E/S) ratio (∼8 μL mg−1) conditions, the battery still delivers an outstanding areal capacity of 11.05 mAh cm−2 after 40 cycles. This work provides a rational strategy for designing high-efficient bidirectional catalyst with single component for high-performance Li-S batteries.

The performance of lignin depolymerization is basically determined by the interunit C–O and C–C bonds. Numerous C–O bond cleavage strategies have been developed, while the cleavage of C–C bond between the primary aromatic units remains a challenging task due to the high dissociation energy of C–C bond. Herein, a multifunctional RuRe alloy catalyst was designed, which exhibited exceptional catalytic activity for the cleavage of both C–O and C–C linkages in a broad range of lignin model compounds (β-1, α-5, 5-5, β-O-4, 4-O-5) and two stubborn lignins (kraft lignin and alkaline lignin), affording 97.5% overall yield of monocyclic compounds from model compounds and up to 129% of the maximum theoretical yield of monocyclic products based on C–O bonds cleavage from realistic lignin. Scanning transmission electron microscopy (STEM) characterization showed that RuRe (1:1) alloy particles with hexagonal close-packed structure were homogeneously dispersed on the support. Quasi-in situ X-ray photoelectron spectroscopy (XPS), and X-ray absorption spectroscopy (XAS) indicate that Ru species were predominantly metallic state, whereas Re species were partially oxidized; meanwhile, there was a strong interaction between Ru and Re, where the electron transfer from Re to Ru was occurred, resulting in great improvement on the capability of C–O and C–C bonds cleavage in lignin conversion.

Background/purpose Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan. Methods A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed. Results Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid. Conclusion Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers. Intracellular glutathione (GSH) detoxification of cisplatin under the catalysis of glutathione S-transferases (GST) plays important roles in the development of cisplatin resistance. Herein, a strategy of “pincer movement” based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy. Specifically, a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid (EA), a GST inhibitor. Responding to high level of intracellular GSH, the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds, which further promotes drug release. Meanwhile, the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance. Moreover, the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma. The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion, GST inhibition, and consequent tumor growth suppression. Overall, this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance, which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.

Xanthine dehydrogenase, a member of the molybdenum enzyme family, participates in purine metabolism and catalyzes the generation of ureides from xanthine and hypoxanthine. However, the mechanisms by which xanthine dehydrogenase affects rice growth and development are poorly understood. In the present study, we identified a mutant with early leaf senescence and reduced tillering that we named early senescence and less-tillering 1 (esl1). Map-based cloning revealed that ESL1 encodes a xanthine dehydrogenase, and it was expressed in all tissues. Chlorophyll content was reduced and chloroplast maldevelopment was severe in the esl1 mutant. Mutation of ESL1 led to decreases in allantoin, allantoate, and ABA contents. Further analysis revealed that the accumulation of reactive oxygen species in esl1 resulted in decreased photosynthesis and impaired chloroplast development, along with increased sensitivity to abscisic acid and abiotic stresses. Ttranscriptome analysis showed that the ESL1 mutation altered the expression of genes involved in the photosynthesis process and reactive oxygen species metabolism. Our results suggest that ESL1 is involved in purine metabolism and the induction of leaf senescence. These findings reveal novel molecular mechanisms of ESL1 gene-mediated plant growth and leaf senescence.

Because of the limited understanding of cellular metabolism and regulatory networks, the rational engineering of complex industrial traits remains a grand challenge for the construction of microbial cell factories. Thus the development of simple, efficient, and programmable genome evolution techniques is still in high demanded for industrial biotechnology. In the present study, we established a random base editing (rBE) system for genome evolution in Saccharomyces cerevisiae. By fusing an unspecific single-stranded DNA (ssDNA)-binding protein to a cytidine deaminase, rBE introduced C to T mutations in a genome-wide manner. Specifically, we chose DNA-replication-related proteins, including replication factor A (RFA1, RFA2, and RFA3), DNA primase (PRI1), DNA helicase A (HCS1), and topoisomerase I (TOP1), to mediate the deamination of genomic ssDNA. As a proof of concept, we roughly estimated the rBE-mediated yeast genome mutation rate using the CAN1 mutation/canavanine resistance reporter system. We then evaluated the performance of these rBEs in improving the resistance against isobutanol and acetate and increasing the production of β-carotene. Finally, we employed the optimal rBE for the continuous genome evolution of a yeast cell factory resistant to 9% isobutanol. Owing to the conservation of DNA replication mechanisms, rBE is generally applicable and theoretically can be adopted for the continuous genome evolution of all organisms.

Histones are the alkali proteins in eukaryotic somatic chromatin cells which constitute the nucleosome structure together with DNA. Their abnormality is often associated with multiple tumorigenesis and other human diseases. Nevertheless, a simple and efficient super-resolution method to visualize histone distribution at the subcellular level is still unavailable. Herein, a Zn(II) terpyridine complex with rich-electronic azide units, namely, TpZnA-His, was designed and synthesized. The initial in vitro and in silico studies suggested that this complex is able to detect histones rapidly and selectively via charge-charge interactions with the histone H3 subunit. Its live cell nuclear localization, red-emission tail, and large Stokes shift allowed super-resolution evaluation of histone distributions with a clear distinction against nuclear DNA. We were able to quantitatively conclude three histone morphology alternations in live cells including condensation, aggregation, and cavity during activating histone acetylation. This work offers a better understanding as well as a versatile tool to study histone-involved gene transcription, signal transduction, and differentiation in cells.

Background Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first‐line treatment of Chinese patients with advanced or recurrent non‐squamous non‐small cell lung cancer (NSCLC). Methods Stage IIIB‐IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4‐6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression‐free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). Results Between December 15th, 2017, and May 15th, 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th, 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1‐6) and median duration of treatment of 3.0 (range 0.0‐5.1) months. ORR of response‐evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80‐1.04, within the prespecified equivalence margin of 0.75‐1.33). Up to May 15th, 2020, with a median follow‐up of 13.6 (range 0.8‐28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1‐year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. Conclusions LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non‐squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non‐squamous NSCLC patients in the first‐line setting., This study demonstrated similarity between LY01008 and reference bevacizumab (Avastin) in terms of efficacy, safety, and immunogenicity in combination with paclitaxel and carboplatin as first‐line treatment in Chinese patients with advanced non‐squamous NSCLC.

Brain energetics disturbance is a hypothesized cause of depression. Glucose is the predominant fuel of brain energy metabolism; however, the cell-specific change of glucose metabolism and underlying molecular mechanism in depression remains unclear. In this study, we firstly applied 18 F-FDG PET and observed brain glucose hypometabolism in the prefrontal cortex (PFC) of corticosterone-induced depression of rats. Next, astrocytic glucose hypometabolism was identified in PFC slices in both corticosterone-induced depression of rats and cultured primary astrocytes from newborn rat PFC after stress-level corticosterone (100 nM) stimulation. Furthermore, we found the blockage of glucose uptake and the decrease of plasma membrane (PM) translocation of glucose transporter 1 (GLUT1) in astrocytic glucose hypometabolism under depressive condition. Interestingly, thioredoxin interacting protein (TXNIP), a glucose metabolism sensor and controller, was found to be over-expressed in corticosterone-stimulated astrocytes in vivo and in vitro. High TXNIP level could restrict GLUT1-mediated glucose uptake in primary astrocytes in vitro. Adeno-associated virus vector-mediated astrocytic TXNIP over-expression in rat medial PFC suppressed GLUT1 PM translocation, consequently developed depressive-like behavior. Conversely, TXNIP siRNA facilitated GLUT1 PM translocation to recover glucose hypometabolism in corticosterone-exposed cultured astrocytes. Notably, astrocyte-specific knockdown of TXNIP in medial PFC of rats facilitated astrocytic GLUT1 PM translocation, showing obvious antidepressant activity. These findings provide a new astrocytic energetic perspective in the pathogenesis of depression and, more importantly, provide TXNIP as a promising molecular target for novel depression therapy.

The monocot lineage-specific miR528 was previously established as a multistress regulator. However, it remains largely unclear how miR528 participates in response to salinity stress in rice. Here, we show that miR528 positively regulates rice salt tolerance by down-regulating a gene encoding l-ascorbate oxidase (AO), thereby bolstering up the AO-mediated abscisic acid (ABA) synthesis and ROS scavenging. Overexpression of miR528 caused a substantial increase in ascorbic acid (AsA) and ABA contents but a significant reduction in ROS accumulation, resulting in the enhanced salt tolerance of rice plants. Conversely, knockdown of miR528 or overexpression of AO stimulated the expression of the AO gene, hence lowering the level of AsA, a critical antioxidant that promotes the ABA content but reduces the ROS level, and then compromising rice tolerance to salinity. Together, the findings reveal a novel mechanism of the miR528-AO module-mediated salt tolerance by modulating the processes of AsA and ABA metabolism as well as ROS detoxification, which adds a new regulatory role to the miR528-AO stress defense pathway in rice.

Background Disseminated nocardiosis is liable to be misdiagnosed owing to the non-specific clinical manifestations and laboratory/imaging findings. Metagenomic next-generation sequencing (mNGS) is a culture-independent and rapid method for direct identification of all microorganisms in clinical specimens. Case presentation A 72-year-old man was admitted to our hospital on February 20, 2019 with a history of recurrent cough, expectoration, fever, and diarrhea since 1 month, and unconsciousness since 1 week. Contrast-enhanced magnetic resonance imaging of head showed multiple lesions in the bilateral cerebral hemispheres, brainstem, and cerebellar hemispheres. The presumptive diagnosis was disseminated tuberculosis, although all tests for mycobacterium were negative. However, the patient did not benefit from antituberculosis treatment. Repeat MRI showed multiple abnormal signals in the brain and progression of meningeal thickening. Cerebrospinal fluid and bronchoalveolar lavage fluid specimens were subsequently sent for PMSeq metagenomics sequencing; the results indicated Nocardia. farcinica as the predominant pathogen. The anti-TB treatment was stopped and the patient was prescribed sulphamethoxazole in combination with linezolid and meropenem for nocardiosis. He showed gradual neurological improvement and was transferred to Huashan Hospital. He was discharged from the hospital on April 19, 2019, but died of persistent diarrhea on May 26, 2019. Conclusions Patients with suspected nocardiosis do not always respond to conventional treatment; therefore, mNGS can facilitate diagnosis and timely treatment decision-making.

Background. The number of hepatocellular carcinoma (HCC) cases worldwide has increased significantly. As a traditional Chinese medicine (TCM) with a long history, Ecliptae herba (EH) has been widely used in HCC patients in China, but its hepatoprotective mechanism is still unclear. Methods. In this study, we applied a network pharmacology-based strategy and experimental verification to systematically unravel the underlying mechanisms of EH against HCC. First, six active ingredients of EH were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) by the ADME method. Subsequently, 52 potential targets of 6 active ingredients acting on HCC were screened from various databases, including TCMSP, DGIdb, SwissTargetPrediction, CTD, and GeneCards. Then, by constructing protein-protein interaction (PPI) network from STRING, we displayed the intricate connections among these 52 targets through Cytoscape software. We also applied enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, to provide an outline and set of concepts for describing gene functions and the advanced functions of biological systems of these 52 targets from genomic and molecular level information. Finally, molecular docking and biological experiments were used to reconfirm these results. Results. We hypothesized that EH might exert anti-HCC activity by acting on hub genes, including RELA, MMP9, PTGS2, ESR1, EGFR, AR, AKT1, HIF1A, AHR, CYP3A4, ABCG2, and MMP2. Moreover, based on GO and KEGG analysis, we speculated that EH may exert hepatoprotective effects on HCC through the following mechanisms: regulation of the PI3K-AKT signaling pathway to promote apoptosis and inhibit the abnormal proliferation of HCC, downregulation of HIF-1A expression by activating the HIF-1 signaling pathway, prevention of HCC by regulating lipid metabolism, and inhibition of nonalcoholic fatty liver disease (NAFLD) by the cytochrome P450 subfamily. Subsequent biological experiments verified that EH inhibits the PI3K-AKT signaling pathway through its active ingredients, quercetin, and wedelolactone, thereby inhibiting the proliferation of HCC cells and promoting the apoptosis of HCC cells. Conclusions. The network pharmacological strategy provides an efficient method to systematically explore the pharmacological mechanism of EH in HCC. Our study demonstrated that the anti-HCC proliferation activity of EH is mainly exerted by two active ingredients (quercetin and wedelolactone), which inhibit the proliferation of HCC cells (HepG2 and Huh-7) by inhibiting PI3K-AKT signaling.

Surgical resection of the tumor remains the preferred treatment for most solid tumors at an early stage, but surgical treatment often leads to massive bleeding and residual tumor cells. Therefore, a novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers (CFAGS) for rapid hemostasis and prevention of tumor recurrence was prepared by using an electrospinning and interpenetrating polymer network (IPN) strategy. The present results show that alginate/gelatin sponge display excellent hemostatic properties and possess more advantages than commercial gelatin hemostasis sponge. More importantly, CFAGS could control the release of curcumin, inducing curcumin to accumulate at the surgical site of the tumor, thereby inhibiting local tumor recurrence in the subcutaneous postoperative recurrence model. In addition, the sponge was safe to implant in the body and did not cause toxicity to normal tissues and organs. This approach represents a new strategy to implant a dual functional sponge at the postoperative site as an adjuvant to the surgical treatment of cancer.

Long-chain omega-3 polyunsaturated fatty acids (LC-PUFAs), known for having many health benefits, are usually present in three forms: triglycerides (TG), ethyl esters (EE), and phospholipid (PL). In this study, the effects of these three LC-PUFAs forms (fish oil for TG and EE, krill oil for PL) on the obese mice were compared, and the proteomic changes that focused on lipid metabolism were evaluated via label-free quantitative proteomics analysis. Compared with the model group, all three of the LC-PUFA form supplementations (labeled as the FO-TG group, FO-EE group and KO-PL groups) could significantly reduce body weight gain (P

The expression of voltage-gated potassium Kv1.3 channels is increased in activated microglia, with non-selective blockade reported to attenuate microglial-mediated neuroinflammation. In this study, we evaluated the impact of a potent and selective peptidic blocker of Kv1.3 channels, HsTX1[R14A], on microglial-mediated neuroinflammation in vitro and in vivo. Treatment with both 0.1 and 1 µg/mL lipopolysaccharide (LPS) significantly (p