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Summary: The advantage of a generalized electric spring (G‐ES) is that it solves the redundancy problem of a conventional electric spring (ES) in the face of critical load clusters. This paper first introduces Hamilton's principle into the G‐ES, derives the mathematical model of the G‐ES, and further introduces the topology of the G‐ES. Next, the working modes and working states of the G‐ES are defined. The working modes are used to reflect the combination of ES power inside the G‐ES, and the power conditions in specific working modes are described using a phase diagram. Then, the paper analyses the power case of the G‐ES to the external system, giving the respective working states according to their internal working modes. Finally, this paper introduces PQ control to the control strategy of the G‐ES and achieves control of the G‐ES working mode and its working state. The results of the study show that there are 100 working modes of the G‐ES, and 76 working modes have a specific working state. The correctness of the working mode and working state analysis is verified with the help of the MATLAB/Simulink simulation and experiment. [ABSTRACT FROM AUTHOR]

Pinhole is a common defect widely seen in many archeological stonewares from different kilns and periods. It is usually a sub‐millimeter pit on the glaze that was believed to be caused by the broken bubbles during the firing process. We investigated the pinholes on a porcelain sherd from Yaozhou kiln of the Song Dynasty (AD 960–1,127), surprisingly, every pinhole corresponds to a flower‐like cluster observed through the microscope. The flower‐like clusters are composed of radial mullite whiskers and ε‐Fe2O3 dendrites, and its growth mechanism were proposed after detailed microscopic and spectroscopic characterizations. The unique chemical composition around the pinholes became the breeding ground for the crystallization of flowers, whereas the crystallization process further facilitates the formation of the pinhole preventing the glaze from restoring smoothness. Our results enriched the knowledge on pinholes and revealed the interesting crystallization assisted formation mechanism, which not only related to bubble rupture but involves the crystallization dynamics as well. [ABSTRACT FROM AUTHOR]

Warfarin is a widely used anticoagulant, and its S‐enantiomer has higher potency compared to the R‐enantiomer. S‐warfarin is mainly metabolized by cytochrome P450 (CYP) 2C9, and its pharmacological target is vitamin K epoxide reductase complex subunit 1 (VKORC1). Both CYP2C9 and VKORC1 have genetic polymorphisms, leading to large variations in the pharmacokinetics (PKs) and pharmacodynamics (PDs) of warfarin in the population. This makes dosage management of warfarin difficult, especially in the case of drug–drug interactions (DDIs). This study provides a whole‐body physiologically‐based pharmacokinetic/PD (PBPK/PD) model of S‐warfarin for predicting the effects of drug–drug−gene interactions on S‐warfarin PKs and PDs. The PBPK/PD model of S‐warfarin was developed in PK‐Sim and MoBi. Drug‐dependent parameters were obtained from the literature or optimized. Of the 34 S‐warfarin plasma concentration‐time profiles used, 96% predicted plasma concentrations within twofold range compared to observed data. For S‐warfarin plasma concentration‐time profiles with CYP2C9 genotype, 364 of 386 predicted plasma concentration values (~94%) fell within the twofold of the observed values. This model was tested in DDI predictions with fluconazole as CYP2C9 perpetrators, with all predicted DDI area under the plasma concentration‐time curve to the last measurable timepoint (AUClast) ratio within twofold of the observed values. The anticoagulant effect of S‐warfarin was described using an indirect response model, with all predicted international normalized ratio (INR) within twofold of the observed values. This model also incorporates a dose‐adjustment method that can be used for dose adjustment and predict INR when warfarin is used in combination with CYP2C9 perpetrators. [ABSTRACT FROM AUTHOR]

Current techniques identifying herbal medicine species require marker labeling or lack systematical accuracy (expert authentication). There is an emerging interest in developing an accurate and label‐free tool for herbal medicine authentication. Here, a high‐resolution microfluidic‐based method is developed for identifying herbal species by protoplast subpopulations. Moso bamboo and henon bamboo are used as a model to be differentiated based on protoplast. Their biophysical properties factors are characterized to be 7.09 (± 0.39) × 108 V/m2 and 6.54 (± 0.26) × 108 V/m2, respectively. Their biophysical distributions could be distinguished by the Cramér–von Mises criterion with a 94.60% confidence level. The subpopulations of each were compared with conventional flow cytometry indicating the existence of subpopulations and the differences between the two species. The subsets divided by a biophysical factor of 8.05(± 0.51) × 108 V/m2 suggest good consistency with flow cytometry. The work demonstrated the possibility of microfluidics manipulation on protoplast for medication safety use taking advantage of dielectrophoresis. The device is promising in developing a reliable and accurate way of identifying herbal species with difficulties in authentication. [ABSTRACT FROM AUTHOR]

Although the development of punctuated equilibrium theory makes broad reference to the bureaucratic procedures that regulate budgetary decision making and makes reasonable assumptions about the influence of those procedures on the dynamic of resource allocation, little is known about how the specific mechanisms work. This has led to a call to understand the processes that cause friction in greater detail. This study examines how budgetary output patterns may be influenced by governments' strategic fiscal choices. Using an approach that highlights the roles of various fiscal policy‐making processes, we found significant deviations of budgetary output patterns in capital projects, restricted funds, and entitlement spending, thus signifying the influence of fiscal practices on resource allocation decisions. We further examined how fiscal influences may be realized in the political process of democratization in Hong Kong. By examining legislative filibuster cases related to capital projects, we found evidence associating democratization with greater institutional friction and consequently with larger budgetary output punctuations. [ABSTRACT FROM AUTHOR]

Abstract: The Lanping Basin in the Nujiang‐Lancangjiang‐Jinshajiang (the Sanjiang) area of northeastern margin of the Tibetan Plateau is an important part of eastern Tethyan metallogenic domain. This basin hosts a number of large unique sediment‐hosted Pb‐Zn polymetallic deposits or ore districts, such as the Baiyangping ore concentration area which is one of the representative ore district. The Baiyangping ore concentration area can be divided into the east and west ore belts, which were formed in a folded tectogene of the India‐Asia continental collisional setting and was controlled by a large reverse fault. Field observations reveal that the Mesozoic and Cenozoic sedimentary strata were outcropped in the mining area, and that the orebodies are obviously controlled by faults and hosted in sandstone and carbonate rocks. However, the ore‐forming elements in the east ore belt are mainly Pb‐Zn‐Sr‐Ag, while Pb‐Zn‐Ag‐Cu‐Co elements are dominant in the west ore belt. Comparative analysis of the C‐O‐Sr‐S‐Pb isotopic compositions suggest that both ore belts had a homogeneous carbon source, and the carbon in hydrothermal calcite is derived from the dissolution of carbonate rock strata; the ore‐forming fluids were originated from formation water and precipitate water, which belonged to basin brine fluid system; sulfur was from organic thermal chemical sulfate reduction and biological sulfate reduction; the metal mineralization material was from sedimentary strata and basement, but the difference of the material source of the basement and the strata and the superimposed mineralization of the west ore belt resulted in the difference of metallogenic elements between the eastern and western metallogenic belts. The Pb‐Zn mineralization age of both ore belts was contemporary and formed in the same metallogenetic event. Both thrust formed at the same time and occurred at the Early Oligocene, which is consistent with the age constrained by field geological relationship. [ABSTRACT FROM AUTHOR]

The Sepikou region is located in the eastern Bogda Mountains of the east Tianshan. The Bogda belt is mainly composed of Carboniferous strata, including the Lower Carboniferous Qijiaojing Formation (C1q), Upper Carboniferous Liushugou Formation (C2l), and Qijiagou Formation (C2qj). Here, we report the petrology, geochemistry, and geochronology of bimodal volcanic rocks from the Upper Carboniferous Liushugou Formation, which is widely distributed in the Sepikou region. The basalts, basaltic andesite, and keratophyre have similar petrochemical characteristics and exhibit the high‐Na, low‐K characteristics belonging to calc‐alkalic rocks. These are characterized by the high abundance of K, Rb, Th, Ba, the depletion of HFSE (Nb, Ta, Zr, and Hf), and the slight depletion of Ti. Chondrite‐normalized rare‐earth elements (REE) patterns for basalts‐keratophyre show right‐leaning parallel curve clusters, together with a slight enrichment in light rare‐earth elements (LREE) contents and low heavy rare‐earth elements (HREE)/LREE ratios. The keratophyre exhibits slightly negative Eu anomalies. Compared with the basalts, the rhyolites have high alkali contents, slightly high ∑REE contents, low heavy rare‐earth elements/LREE ratios, negative εSr(t) (−9.1 to −12.0), low 87Sr/86Sr initial ratio, highly positive εNd (t) (+5.3 to +6.4), and low Pb isotope ratios. The fractionated REE patterns with prominent negative Eu anomalies suggest they were chiefly derived from the mantle magma underplated basaltic body remelting from the depleted mantle source. The LA‐ICP‐MS analysis on zircons from quartz keratophyre and rhyolite yield similar ages of 314.9 ± 1.2 and 314.0 ± 1.1 Ma, respectively, suggest that the major bimodal volcanism took place in the Late Carboniferous epoch. The quartz keratophyre zircons, with the 176Hf/177Hf ratios of 0.282897–0.283097, have highly positive εHf (10.99–19.97) and depleted mantle model ages between 180 and 628 Ma. The mafic rocks were chiefly derived from the depleted mantle with the partial incorporation of crustal components. The bimodal volcanic rocks were formed under a continental rift setting. The rift experienced extension in the early period of the Early Carboniferous and its final closure arose after a late period of the Late Carboniferous. [ABSTRACT FROM AUTHOR]

In this work, nickel‐modified graphene nanosheets (Ni−G) were prepared by hydrothermal method for the first time. The microscopic morphological analysis showed that the nickel nanoparticles were successfully reductively deposited on the surface of Ni−G with uniform distribution. Ni−G can be uniformly and stably dispersed in the electrodeposition solution. Then Ni/Co/Ni−G composite coating was prepared by pulsed current co‐deposition method to provide corrosion resistance protection for Q235 carbon steel. The microstructure and morphology analysis of the composite coating shows that Ni−G were homogeneously incorporated in the coating and the composite coatings were uniform, dense and crack‐free. The hardness test results showed that the doping of Ni−G improved the hardness of the composite coating. The influence of the added amount of Ni−G in the electrodeposition solution on the anti‐corrosion performance of the composite coating was investigated. The electrochemical results illustrated that the composite coating prepared by adding 20 mL Ni−G dispersion achieved 98.04 % protection efficiency (η ${\eta }$ EIS) against carbon steel substrate in 3.5 wt.% NaCl solution, the Ni/Co/Ni−G20 composite coating has the best corrosion resistance. [ABSTRACT FROM AUTHOR]

Emerging flexible and wearable electronic products are placing a compelling demand on lightweight transparent energy storage devices. Owing to their distinguishing features of safety, high specific energy, cycling stability, and rapid charge/discharge advantages, Zn‐ion hybrid supercapacitors are a current topic of discussion. However, the trade‐off for optical transmittance and energy density remains a great challenge. Here, a high‐performance Zn‐ion hybrid supercapacitor based on the customizable ultrathin (5 µm), ultralight (0.45 mg cm−2), and ultra‐transparent (87.6%) Ni micromesh based cathode and Zn micromesh anode with the highest figure of merit (84 843) is proposed. The developed flexible transparent Zn‐ion hybrid supercapacitors reveal excellent cycle stability (no decline after 20 000 cycles), high areal energy density (31.69 µWh cm−2), and high power density (512 µW cm−2). In addition, the assembled solid flexible and transparent Zn‐ion hybrid supercapacitor with polyacrylamide gel electrolyte shows extraordinary mechanical properties even under extreme bending and twisting operation. Furthermore, the full device displays a high optical transmittance over 55.04% and can be conformally integrated with diverse devices as a flexible transparent power supply. The fabrication technology offers seamless compatibility with industrial manufacturing, making it an ideal model for the advancement of portable and wearable devices. [ABSTRACT FROM AUTHOR]

Background and aims: The existing evidence has indicated that hyperthermia ablation (HA) and HA combined with transarterial chemoembolization (HATACE) are the optimal alternative to surgical resection for patients with hepatocellular carcinoma (HCC) in the COVID‐19 crisis. However, the evidence for decision‐making is lacking in terms of comparison between HA and HATACE. Herein, a comprehensive evaluation was performed to compare the efficacy and safety of HATACE with monotherapy. Materials and Methods: Worldwide studies were collected to evaluate the HATACE regimen for HCC due to the practical need for global extrapolation of applicative population. Meta‐analyses were performed using the RevMan 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Results: Thirty‐six studies involving a large sample of 5036 patients were included finally. Compared with HA alone, HATACE produced the advantage of 5‐year overall survival (OS) rate (OR:1.90; 95%CI:1.46,2.46; p < 0.05) without increasing toxicity (p ≥ 0.05). Compared with TACE alone, HATACE was associated with superior 5‐year OS rate (OR:3.54; 95%CI:1.96,6.37; p < 0.05) and significantly reduced the incidences of severe liver damage (OR:0.32; 95%CI:0.11,0.96; p < 0.05) and ascites (OR:0.42; 95%CI:0.20,0.88; p < 0.05). Subgroup analysis results of small (≤3 cm) HCC revealed that there were no significant differences between the HATACE group and HA monotherapy group in regard to the OS rates (p ≥ 0.05). Conclusions: Compared with TACE alone, HATACE was more effective and safe for HCC. Compared with HA alone, HATACE was more effective for non‐small‐sized (>3 cm) HCC with comparable safety. However, the survival benefit of adjuvant TACE in HATACE regimen was not found for the patients with small (≤3 cm) HCC. [ABSTRACT FROM AUTHOR]

Aim: Many studies have found that diazotrophic distribution is mainly determined by soil properties from field to regional scales. However, we lack strong evidence for the relative importance of different drivers controlling broad‐scale biogeography of forest diazotrophs, especially for soil multi‐nutrients. Location: China's forests. Time period: 2012−2013. Major taxa studied: Diazotrophic communities. Methods: We investigated the distribution of soil diazotrophic communities from 146 sites along a 3,900‐km south–north transect by sequencing N‐fixing nifH gene amplicons. The relative contributions of environmental variables were assessed using a combination of stepwise multiple regression, variation partitioning analysis, multiple regression on distance matrices and partial least squares path modelling. Results: Overall, aridity index and temperature were the predominant parameters governing diazotrophic community diversity and structure, mainly through their indirect effects on soil pH, nutrient contents and plant productivity. Although soil multi‐nutrients (Ca, Mg, Fe, Mn, Na, Cu and Zn) were included in the statistical analysis, they still exhibited lower impacts on diazotrophic communities than climate. Intriguingly, the microelement Mo could not explain the diazotrophic community patterns, despite its significance in nitrogenase enzymes. This unexpected phenomenon was attributed to the relatively high Mo supply in our work. Moreover, the distinct responses of diazotroph taxa to climatic factors and large heterogeneity of diazotrophic diversity among forests in different climatic zones further support the dominant role of climatic variation. These results indicate the presence of differentiated climatic niches for diazotrophs, such as warm‐adapted Bradyrhizobium and cool‐adapted Azospirillum. Main conclusions: Our findings suggest for the first time that unlike prior studies, the key roles of soil nutrient limitation (even for Mo) and pH‐dependent mechanisms in small‐scale diazotrophic communities can be surpassed by large‐scale climatic gradients. Future changes in drought severity and temperature might greatly shape diazotrophic distribution and its potential function in forest N2 fixation. [ABSTRACT FROM AUTHOR]

Gravity‐drainage‐assisted steam flooding is a new technology to improve the recovery factor after deep penetration in deep super‐heavy oil reservoirs. This study is based on a model of the 60‐H25 test well group in Block 59 in Liaohe Oilfield, China. The numerical model uses the C programming language to analyze the influence of change in the bottom water height on the drainage effect and provides a theoretical basis for physical model experiments and field production. The physical model experiment uses similar principles to describe the production characteristics at different stages in a short cycle. We combine the numerical model and the physical model experiment to analyze the production rule of the Wa59 block over a long time period. The results show that the physical model experiment and the actual production of the block reflect the productivity change law of the well group, the degree of production, and the productivity relationship of the well group over short cycles and long periods, respectively. The comparison showed that the actual production was consistent with the production model of the physical model test, and the drainage effect was verified. The study of gravity‐drainage‐assisted steam flooding provides a reliable basis for the next stage of oilfield production. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effect of intrathecal (i.t.) serotonin (5‐hydroxytryptamine) 5‐HT7 agonist administration on voiding function in the urethane‐anesthetised rat, and the change in 5‐HT7 receptor (5‐HT7R) expression in the lumbosacral cord Onuf's nucleus after spinal cord injury (SCI). Materials and methods: In all, 32 female Sprague–Dawley (SD) rats were equally divided into a spinally intact (SI) group and SCI group (n = 16 each). At 8 weeks after transection, half of the rats underwent continuous cystometry under urethane anaesthesia, and the 5‐HT7R‐selective agonist LP44 was given (i.t.). The remaining rats were used for pseudorabies (PRV) retrograde tracing, immunofluorescence, and Western Blot. Results: LP44 administered i.t. had no effect in the SI rats. In SCI rats, LP44 (1–30 μg/kg) induced significant dose‐dependent increases in micturition volume, voiding efficiency, number of high‐frequency oscillations per micturition; and decreases in residual volume, bladder capacity, peak bladder pressure, threshold pressure and non‐voiding contractions. The 5‐HT7R antagonist, SB‐269970 (10 μg/kg), partially reversed LP44‐induced changes. Using PRV retrograde tracing and immunofluorescence, 5‐HT7Rs were found in the L6–S1 spinal cord Onuf's nucleus in both SI and SCI rats, but the expression was significantly greater in the SCI rats. Western blot showed significantly more 5‐HT7Rs in the ventral L6–S1 spinal cord in SCI rats. Conclusion: A 5‐HT7R agonist, given i.t., improved voiding efficiency in urethane‐anesthetised SCI rats, and the 5‐HT7R was significantly up‐regulated in the lumbosacral cord Onuf's nucleus. If valid for humans, these findings suggest that the 5‐HT7R could be a target for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effect of intrathecal (i.t.) serotonin (5‐hydroxytryptamine) 5‐HT7 agonist administration on voiding function in the urethane‐anesthetised rat, and the change in 5‐HT7 receptor (5‐HT7R) expression in the lumbosacral cord Onuf's nucleus after spinal cord injury (SCI). Materials and methods: In all, 32 female Sprague–Dawley (SD) rats were equally divided into a spinally intact (SI) group and SCI group (n = 16 each). At 8 weeks after transection, half of the rats underwent continuous cystometry under urethane anaesthesia, and the 5‐HT7R‐selective agonist LP44 was given (i.t.). The remaining rats were used for pseudorabies (PRV) retrograde tracing, immunofluorescence, and Western Blot. Results: LP44 administered i.t. had no effect in the SI rats. In SCI rats, LP44 (1–30 μg/kg) induced significant dose‐dependent increases in micturition volume, voiding efficiency, number of high‐frequency oscillations per micturition; and decreases in residual volume, bladder capacity, peak bladder pressure, threshold pressure and non‐voiding contractions. The 5‐HT7R antagonist, SB‐269970 (10 μg/kg), partially reversed LP44‐induced changes. Using PRV retrograde tracing and immunofluorescence, 5‐HT7Rs were found in the L6–S1 spinal cord Onuf's nucleus in both SI and SCI rats, but the expression was significantly greater in the SCI rats. Western blot showed significantly more 5‐HT7Rs in the ventral L6–S1 spinal cord in SCI rats. Conclusion: A 5‐HT7R agonist, given i.t., improved voiding efficiency in urethane‐anesthetised SCI rats, and the 5‐HT7R was significantly up‐regulated in the lumbosacral cord Onuf's nucleus. If valid for humans, these findings suggest that the 5‐HT7R could be a target for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Levetiracetam (LEV) is an anti‐epileptic drug approved for use in various populations. The pharmacokinetic (PK) behavior of LEV may be altered in the elderly and patients with renal and hepatic impairment. Thus, dosage adjustment is required. This study was conducted to investigate how the physiologically‐based PK (PBPK) model describes the PKs of LEV in adult and elderly populations, as well as to predict the PKs of LEV in patients with renal and hepatic impairment in both populations. The whole‐body PBPK models were developed using the reported physicochemical properties of LEV and clinical data. The models were validated using data from clinical studies with different dose ranges and different routes and intervals of administration. The fit performance of the models was assessed by comparing predicted and observed blood concentration data and PK parameters. It is recommended that the doses be reduced to ~70%, 60%, and 45% of the adult dose for the mild, moderate, and severe renal impairment populations and ~95%, 80%, and 57% of the adult dose for the Child Pugh‐A (CP‐A), Child Pugh‐B (CP‐B), and Child Pugh‐C (CP‐C) hepatic impairment populations, respectively. No dose adjustment is required for the healthy elderly population, but dose reduction is required for the elderly with organ dysfunction accordingly, on a scale similar to that of adults. A PBPK model of LEV was successfully developed to optimize dosing regimens for special populations. [ABSTRACT FROM AUTHOR]

Age‐related immune dysfunctions, such as decreased T‐cell output, are closely related to pathologies like cancers and lack of vaccine efficacy among the elderly. Engineered fusokine, GIFT‐7, a fusion of interleukin 7 (IL‐7) and GM‐CSF, can reverse aging‐related lymphoid organ atrophy. We generated a GIFT‐7 fusokine tumor vaccine and employed it in aged syngeneic mouse models of glioblastoma and found that peripheral vaccination with GIFT‐7TVax resulted in thymic regeneration and generated durable long‐term antitumor immunity specifically in aged mice. Global cytokine analysis showed increased pro‐inflammatory cytokines including IL‐1β in the vaccinated group that resulted in hyperactivation of dendritic cells. In addition, GIFT‐7 vaccination resulted in increased T‐cell trafficking to the brain and robust Th‐17 long‐term effector memory T‐cell formation. TCR‐seq analysis showed increased productive frequency among detected rearrangements within the vaccinated group. Overall, our data demonstrate that aging immune system can be therapeutically augmented to generate lasting antitumor immunity. [ABSTRACT FROM AUTHOR]

Flexible Zn‐ion batteries (ZIBs) emerge as a promising entrant for flexible and safe energy systems in the post‐Li era, while the instability of Zn anode including inferior flexibility, uncontrollable plating, and dendrite growth remains a challenge. Naturally inspired, a topology‐optimized biomimetic honeycomb Zn (BH‐Zn) anode through mechanical‐electrochemical processing is demonstrated. Numerical simulations and experimental observations reveal the BH‐Zn engenders smooth current–stress–thermal field distributions, concurrently realizing the multi‐field regulation effect and boosted stability. After in situ alloying, the BH‐Zn enables half‐diminished voltage polarization, superior electrochemical stability of 2000 h cycling, and thermal stability even at 30 mA cm−2. Moreover, the assembled ZIBs manifest over 20 times enhanced capacity retention and are integrated as a self‐powered wearable system for real‐time health monitoring. This strategy can be extended to customizable metal anodes and promises to be applied in stable flexible batteries. [ABSTRACT FROM AUTHOR]

STAT3 phosphorylation at tyrosine 705 (STAT3pY705), triggered by the addition of the leukemia inhibitory factor (LIF), can maintain mouse embryonic stem cell (mESC) self‐renewal and reprogram mouse epiblast stem cells (EpiSCs) to enter a naïve pluripotent state. The activation of STAT3pY705 occurs mainly through Janus kinases. However, it remains unclear how STAT3pY705 levels are decreased in mESCs. Our study shows that upregulation of the protein tyrosine phosphatase (PTPN2) inhibits STAT3 activity by reducing its phosphorylation level and promotes mESC differentiation, whereas PTPN2 knockout by CRISPR/CAS9 delays mESC differentiation. Consistently, PTPN2 knockdown facilitates the generation of mESC‐like colonies in STAT3‐overexpressing EpiSCs. PTPN2‐mediated STAT3 activity, thus, contributes to the exit of ESCs from the pluripotent ground state. These findings expand the current understanding of the regulatory network of naïve pluripotency. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether the voiding dysfunction caused by spinal cord injury (SCI) in rats can be improved by i.v. administration of the serotonin (5‐HT)2A/2C receptor agonist 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropanehydrochloride (DOI), and to discuss whether the mechanism can be ascribed to 5‐HT2A and 5‐HT 2C receptor upregulation in lumbosacral cord motoneurons. Materials and Methods: Female Sprague–Dawley rats were divided into two groups (SCI group vs normal control [NC] group). Under urethane anaesthesia, cystometry was performed to examine the variation in urodynamic variables before and after successive intrathecal (i.t.) administration of various doses of DOI into the lumbosacral cord. Changes in 5‐HT2A and ‐2C receptors in the lumbosacral cord were also investigated using immunohistochemical staining and Western blot analysis. Results: Compared with NC rats, the SCI rats had higher bladder capacity and post‐void residual urine volume, and lower voiding efficiency. After SCI, DOI improved voiding efficiency, probably via external urethral sphincter (EUS) activity. Immunohistochemical staining and Western blot analysis showed that 5‐HT2A and ‐2C receptors were upregulated in lumbosacral cord motoneurons. Conclusion: In rats with SCI, DOI can improve voiding efficiency; this may be attributable to 5‐HT2A and ‐2C receptor upregulation in lumbosacral cord motoneurons controlling EUS activity. [ABSTRACT FROM AUTHOR]

Benzothiazole (II) and benzoxazole (VI) can be efficiently coupled with aryl iodides under optimized conditions A). [ABSTRACT FROM AUTHOR]

Aim: Methane oxidation driven by soil aerobic methanotrophs exhibits the largest methane sink capacity in forest ecosystems and plays important roles in the alleviation of global warming. Many studies have revealed the distribution of methanotrophs in forest ecosystems at field scales; however, the biogeographical patterns of methanotrophic communities and related ecological processes and the drivers shaping methanotrophic communities at a large scale remain poorly understood. Location: China's forests. Time period: 2012–2013. Major taxa studied: Methanotrophic communities. Methods: We evaluated the geographical distributions of soil methanotrophic communities across 26 forests along a 4,000‐km north–south transect in China using a MiSeq high‐throughput sequencing technique. The assembly processes and drivers of the methanotrophic communities were evaluated using the phylogenetic null model approach and structural equation modelling, respectively. Results: The results showed that the upland soil cluster α (USCα) and ammonia‐ oxidizing bacteria‐related (AOB‐rel) methanotrophs were the most abundant taxa in forest soils and exhibited contrasting distributions of relative abundance across different climate zones, suggesting that they occupy different environmental niches. The α‐diversity pattern of the soil methanotrophic community followed a hump‐shaped pattern along a large latitudinal gradient. Statistical analyses suggest that aridity and vegetation productivity [here represented with the normalized difference vegetation index (NDVI)] are major drivers of the α‐diversity of the methanotrophic community, whereas soil pH is the key environmental factor shaping the β‐diversity of the methanotrophic community at a large scale. Additionally, the community assembly of the methanotrophs primarily resulted from deterministic processes, among which heterogeneous selection had a greater contribution in shaping the methanotrophic community than homogeneous selection. Main conclusions: Our study provides new insights into the biogeographical distributions, assembly processes and ecological predictors of the methanotrophic community in forest soil at a large scale. These results can be used to improve simulation models for the better prediction of ecosystem functions under predicted global changes. [ABSTRACT FROM AUTHOR]

Background: A combination of programmed cell death protein‐1 (PD‐1)/programmed cell death ligand‐1 (PD‐L1) inhibitors and radiotherapy (RT) is increasingly being used to treat non‐small‐cell lung cancer (NSCLC). However, the safety and efficacy of this approach remains controversial. We performed a systematic review and meta‐analysis to summarize the related research. Methods: We searched the China Biology Medicine, EMBASE, Cochrane Library, and PubMed databases for all the relevant studies. The Stata software, version 12.0 was used for the meta‐analysis. Results: The study included 20 clinical trials that enrolled 2027 patients with NSCLC. Compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT was associated with prolonged overall survival (OS) (1‐year OS: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.35–2.33, p = 0.000; 2‐year OS: OR 1.77, 95% CI 1.35–2.33, p = 0.000) and progression‐free survival (PFS) (0.5‐year PFS: OR 1.83, 95% CI 1.13–2.98, p = 0.014; 1‐year PFS: OR 2.09, 95% CI 1.29–3.38, p = 0.003; 2‐year PFS: OR 2.47, 95% CI 1.13–5.37, p = 0.023). Combination therapy also improved the objective response rate (OR 2.76, 95% CI 1.06–7.19, p = 0.038) and disease control rate (OR 1.80, 95% CI 1.21–2.68, p = 0.004). This meta‐analysis showed that compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT did not increase the serious adverse event rates (≥grade 3); however, this approach increased the rate of grade 1–2 immune‐related or radiation pneumonitis. Subgroup analyses revealed that the sequence of PD‐1/PD‐L1 inhibitors followed RT outperformed in which concurrent PD‐1/PD‐L1 inhibitor and RT followed PD‐1/PD‐L1 inhibitor. Combination of stereotactic body RT or stereotactic radiosurgery with PD‐1/PD‐L1 inhibitors may be more effective than a combination of conventional RT with PD‐1/PD‐L1 inhibitors in patients with advanced NSCLC. Conclusion: Combination therapy using PD‐1/PD‐L1 inhibitors and RT may improve OS, PFS, and tumor response rates without an increase in serious adverse events in patients with advanced NSCLC. However, combination therapy was shown to increase the incidence of mild pneumonitis. [ABSTRACT FROM AUTHOR]

Background: This study's initial results revealed significant decreases in treatment‐related esophagitis and pneumonitis cases in patients with thoracic esophageal squamous cell carcinoma (ESCC) treated with involved‐field irradiation (IFI), compared to elective nodal irradiation (ENI). This report outlines the long‐term trial results, specifically; overall survival (OS), progression‐free survival (PFS), metastasis‐free survival (MFS), and locoregional progression‐free survival (LRFS). Materials and Methods: Stage II–III thoracic ESCC patients were assigned randomly, in a 1:1 ratio, into either the ENI or IFI arm. Radiation therapy was delivered once a day in 1.8‐2.0 Gy fractions to a total dose of 60.0‐66.0 Gy to the gross tumor volume and 50.0‐54.0 Gy to the clinical target volume. The primary endpoints were acute treatment‐related esophagitis and pneumonitis. The results for the primary endpoints were previously published in 2018. In this article, we analyzed the secondary endpoints including PFS, LRFS, MFS, and OS. Results: Between April 2012 and October 2016, 228 patients from nine participating centers in China were enrolled into this study and randomly assigned to two treatment groups. For ENI and IFI groups, respectively, the results showed similarity and were as follows: median PFS (20.3 months vs 21.4 months), OS (32.5 months vs 34.9 months), MFS (28.2 months vs 26.0 months), and LRFS (25.0 months vs 26.6 months). In particular, respective OS rates in the ENI and IFI groups were 84.6% and 82.5% after 1 year, 45.1% and 48.7% after 3 years, and 29.8% and 30.7% at 5 years. PFS rates after 1, 3, and 5 years were 58.9%, 34.2%, and 26.9%, respectively, in the ENI arm compared to 64.4%, 30.8%, and 27.7%, respectively, in the IFI arm. Multivariate analysis identified clinical stage and tumor responses as independent predictors of OS. Meanwhile, tumor location, cStage, and tumor response were identified as independent factors influencing PFS. Conclusion: IFI was associated with similar survival as ENI in patients with thoracic ESCC, suggesting that IFI is an acceptable treatment method for thoracic ESCC. [ABSTRACT FROM AUTHOR]

Malignant melanomas (MMs) were the fifth most common cancer in men and the sixth most common cancer in women in 2018, respectively. These are characterized by high metastatic rates and poor prognoses. We systematically reviewed safety and efficacy of carbon‐ion radiotherapy (CIRT) for treating MMs. Eleven studies were eligible for review, and the data showed that MM patients showed better local control with low recurrence and mild toxicities after CIRT. Survival rates were slightly higher in patients with cutaneous or uveal MMs than in those with mucosal MMs. CIRT in combination with chemotherapy produced higher progression‐free survival rates than CIRT only. In younger patients, higher rates of distant metastases of gynecological MMs were observed. The data indicated that CIRT is effective and safe for treating MMs; however, a combination with systemic therapy is recommended to ensure the best possible prognosis for MMs. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of a young systemic environment and growth differentiation factor 11 (GDF‐11) on aging cartilage. Methods: A heterochronic parabiosis model (2‐month‐old mouse and 12‐month‐old mouse [Y/O]), an isochronic parabiosis model (12‐month‐old mouse and 12‐month‐old mouse [O/O]), and 12‐month‐old mice alone (O) were evaluated. Knee joints and chondrocytes from old mice were examined by radiography, histology, cell proliferation assays, immunohistochemistry, Western blotting, and quantitative reverse transcriptase–polymerase chain reaction 16 weeks after parabiosis surgery. GDF‐11 was injected into 12‐month‐old mouse joints daily for 16 weeks. Cartilage degeneration, cell proliferation, and osteoarthritis‐related gene expression were evaluated. Results: Osteoarthritis Research Society International scores in old mice were significantly lower in the Y/O group than in the O/O and O groups (both P < 0.05). The percentage of 5‐ethynyl‐2′‐deoxyuridine–positive chondrocytes in old mice was significantly higher in the Y/O group than in the other groups (P < 0.05). Type II collagen (CII) and SOX9 messenger RNA levels differed in cartilage from old mice in the Y/O group compared to the O/O and O groups (both P < 0.05). RUNX‐2, CX, and matrix metalloproteinase 13 levels were significantly lower in cartilage from old mice in the Y/O group compared to the O/O and O groups (both P < 0.05). Similar results were obtained for protein expression levels and after GDF‐11 treatment in vitro and in vivo. Phosphorylated Smad2/3 (pSmad2/3) levels were higher in the recombinant GDF‐11–treated group than in the control group. Conclusion: A young systemic environment promotes chondrocyte proliferation and cartilage matrix synthesis in old mice. GDF‐11, a "young factor," contributes to these effects through the up‐regulation of pSmad2/3. [ABSTRACT FROM AUTHOR]

Tfcp2l1 is a transcription factor critical for mouse embryonic stem cell (mESC) maintenance. However, its role in human ESCs (hESCs) remains unclear. Here, we investigated the role of Tfcp2l1 in controlling hESC activity and showed that Tfcp2l1 is functionally important in the maintenance of hESC identity. Tfcp2l1 expression is highly enriched in hESCs and dramatically decreases upon differentiation. Forced expression of Tfcp2l1 promoted hESC self-renewal. Functional analysis of the mutant forms of Tfcp2l1 revealed that both the CP2- and SAM-like domains are indispensable for Tfcp2l1 to maintain the undifferentiated state of hESCs. Notably, the CP2-like domain is closely related to the suppression of definitive endoderm and mesoderm commitment. Accordingly, knockdown of Tfcp2l1 significantly induced differentiation preferentially into definitive endoderm and mesoderm. Further studies found that inhibition of Wnt/β-catenin signaling pathway by IWR1 is able to eliminate the differentiation caused by Tfcp2l1 downregulation. Taken together, these findings reveal the unique and crucial role of Tfcp2l1 in the determination of hESC fate and will expand our understanding of the self-renewal and differentiation circuitry in hESCs. [ABSTRACT FROM AUTHOR]

Previously, our laboratory identified ECE-1, encoding endothelin-converting enzyme-1 (ECE-1), as a positional candidate for a pleiotropic quantitative trait locus affecting femoral size, shape, and biomechanical performance. We hypothesized that endothelin-1 (ET-1) signaling promotes osteogenesis. Exposure of immortalized mouse osteoblast (TMOb) cells to big ET-1 increased mineralization. Following big ET-1 treatment, we measured the secretion of insulin-like-growth factor-1 (IGF1), dickkopf-homolog-1 protein 1 (DKK1), and sclerostin (SOST). In each case, big ET-1 signaling changed secretion in a manner that favored increased osteogenic activity. Treatment with ECE-1, endothelin receptor A (EDNRA), or WNT receptor antagonists inhibited the big ET-1-mediated increase in mineralization. In the presence of big ET-1, message levels of Runx2, Igf1, Dkk1, and Sost are uncoupled from protein production, suggesting posttranscriptional regulation. To evaluate the role of big ET-1 in normal bone physiology, we inhibited EDNRA signaling during mineralization in the absence of exogenous ET-1. EDNRA blockade reduced mineralization, decreased IGF1, and increased DKK1 and SOST secretion, responses opposite to those induced by exogenous big ET-1. Pharmacological and siRNA knockdown to inhibit ECE-1 reduced mineralization and IGF1 secretion with decreasing DKK1 and decreasing or stable SOST secretion, suggesting a further, unknown role of ECE-1 in osteoblast maturation. Previously we identified miR 126-3p as a potential ET-1-responsive regulator of SOST in murine cells. Overexpression of miR126-3p increased mineralization in TMOb cells and decreased SOST secretion. Osteoblasts express the ET-1 signaling pathway and ET-1 signaling is necessary for normal osteoblast differentiation and mineralization, acting through regulation of miRs that target osteogenic molecules. [ABSTRACT FROM AUTHOR]