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Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro‐inflammatory cytokine interleukin (IL)‐1β, IL‐6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF‐κB) subunit p65 by DHEA and weakened the transcriptional activity of NF‐κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF‐κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2‐Foxo1‐GSH‐NF‐κB pathway. [ABSTRACT FROM AUTHOR]

Over 218 million tonnes of oil palm trunks (OPT) waste is produced annually by Malaysian oil palm industry, which can be converted to biofuels via wet torrefaction. This study assessed the fuel characteristics of wet torrefied OPT (WT‐OPT) using proximate analysis, higher heating value (HHV) analysis, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy–energy dispersive X–ray spectroscopy (SEM–EDX). Increasing wet torrefaction temperature and residence time increased the fixed carbon content and HHV of OPT. SEM–EDX revealed the presence of microspheres of 5‐hydroxymethylfurfural (5‐HMF) in OPT wet torrefied at 180 and 220°C for 72 h, an intermediate compound that can contribute to the HHV enhancement in WT‐OPT. FTIR and EDX results revealed that higher temperature and residence time concentrate the carbon content of OPT. Wet torrefaction at 180°C for 72 h decreased the activation energy and pre‐exponential factor of OPT from 301.88 to 171.70 kJ mol−1 and from 4.43 × 1028 to 3.25 × 1012 s−1, respectively, during pyrolysis. The estimated thermodynamic parameters, particularly the change in entropy which generally decreased by more than 140 J mol−1 K−1, indicated increase in stability of certain WT‐OPT. [ABSTRACT FROM AUTHOR]

Aim Methodology Results Conclusions This study investigated the effects of the inflammatory microenvironment of moderate pulpitis on biological properties of human dental pulp stem cells (DPSCs) and further explored the mechanism involved in osteo‐/odontogenic induction of the inflammatory microenvironment.Healthy DPSCs (hDPSCs) and inflammatory DPSCs (iDPSCs) were isolated from human‐impacted third molars free of caries and clinically diagnosed with moderate pulpitis, respectively. Healthy DPSCs were treated with lipopolysaccharides (LPS) to mimic iDPSCs in vitro. The surface markers expressed on hDPSCs and iDPSCs were detected by flow cytometry. A CCK‐8 assay was performed to determine cell proliferation. Flow cytometric analysis was used to evaluate cell apoptosis. The osteo‐/odontogenic differentiation of DPSCs was evaluated by western blot, alkaline phosphatase staining, and Alizarin Red S staining. The functions of the genes of differentially expressed mRNAs of hDPSCs and iDPSCs were analysed using gene set enrichment analysis. Transmission electron microscopy and western blot were used to evaluate the autophagy changes of LPS‐treated DPSCs.Compared with hDPSCs, iDPSCs showed no significant difference in proliferative capacity but had stronger osteo‐/odontogenic potential. In addition, the mRNAs differentially expressed between iDPSCs and hDPSCs were considerably enriched in autophagosome formation and assembly‐related molecules. In vitro mechanism studies further found that low concentrations of LPS could upregulate DPSC autophagy‐related protein expression and autophagosome formation and promote its odontogenic/osteogenic differentiation, whereas the inhibition of DPSC autophagy led to the weakening of the odontogenic/osteogenic differentiation induced by LPS.This explorative study showed that DPSCs isolated from teeth with moderate pulpitis possessed higher osteo‐/odontogenic differentiation capacity, and the mechanism involved was related to the inflammatory microenvironment‐mediated autophagy of DPSCs. This helps to better understand the repair potential of inflamed dental pulp and provides the biological basis for pulp preservation and hard tissue formation in minimally invasive endodontics. [ABSTRACT FROM AUTHOR]

What is the most favorite and original chemistry developed in your research group? We originally proposed the design principle for molecular ferroelectrics: ferroelectrochemistry, including quasi‐spherical theory, the introduction of homochirality, and H/F substitution. Ferroelectrochemistry changed the blind search for molecular ferroelectrics into targeted chemical design, which will develop into a new discipline. How do you get into this specific field? Could you please share some experiences with our readers? I have been devoted to the field of molecular ferroelectrics for more than 20 years. In the early stage, I worked on non‐centrosymmetric metal‐organic complexes, which are potential molecular ferroelectrics. This laid a foundation for my further study of molecular ferroelectrics. Non‐centrosymmetric crystal symmetry is only one of the necessary requirements for ferroelectrics, which must adopt one of the 10 polar crystallographic point groups and should also generally undergo symmetry‐breaking phase transitions. Due to the lack of a feasible method, the discovery of molecular ferroelectrics has long depended on blindly searching. This process is like finding a needle in a haystack. After years of exploration in this field, I fully understood the Landau phase transition phenomenological theory, Curie symmetry, and Neumann principle from a chemical perspective, and proposed the design principle for molecular ferroelectrics: ferroelectrochemistry, transforming the discovery of molecular ferroelectrics from blind search to targeted chemical design. Never give up no matter how much difficulty you have met, because maybe there is an opportunity the next second. What is the most important personality for scientific research? Curiosity, divergent thinking, perseverance, team spirit, and gratitude. How do you supervise your students? Emphasis on independent problem‐solving abilities. Encourage students to read professional books frequently while doing research. What are your hobbies? What's your favorite book(s)? Jogging, reading, and swimming. My favorite book is The Journey to the West. Comprehensive Summary: Molecular ferroelectrics have attracted tremendous attention in the past decades due to their excellent ferroelectric performance and superiorities of easy processability, mechanical flexibility, and good biocompatibility. However, the discovery of molecular ferroelectrics is a great challenge and has long relied on blind search. This situation changed recently, with the development of ferroelectrochemistry proposed by our group. As a major design approach in ferroelectrochemistry, introducing homochirality, which facilitates the crystallization of materials in polar crystallographic point groups, greatly improves the probability of being ferroelectrics. Various new molecular ferroelectrics with splendid properties have been precisely synthesized by using this efficient and universal strategy. In this review, we summarize the advances in the chemical design of molecular ferroelectrics through the strategy of introducing homochirality. Key Scientists: [ABSTRACT FROM AUTHOR]

Introduction: During the COVID‐19 pandemic, there was a sharp decline in blood donation which posed a serious threat to the clinical blood supply worldwide. The aim of this study was to evaluate the influence of the COVID‐19 pandemic on blood donation and supply in China on a nationwide level. Methods: A comprehensive review of the published literature was performed using eight databases including PubMed, Web of Science, Cochrane Library, Ovid, Embase, CNKI, WANFANG, and VIP by searching relevant words combinations. Results: Twenty‐seven studies were determined to be eligible and included. Among them, 21 studies reported the situation of blood donation during the COVID‐19 pandemic in China. The donation of both whole blood and platelet concentrates declined (with a decline of 5%–86% for whole blood and 3%–34% for platelet concentrates), with this especially evident in February 2020. The COVID‐19 pandemic changed the pattern of blood donation and the composition of blood donors accordingly. Fifteen articles reported the supply of various blood components during the COVID‐19 pandemic. The supply and usage of both packed red blood cell (PRBC) and fresh‐frozen plasma (FFP) decreased (with a decrease of 4%–40% for PRBC and 9%–58% for FFP). The proportion of blood transfusions in different departments changed too. Compared to 2019, there was a decrease in surgical blood transfusions, and an increase in that used in treatments performed in emergency and internal medicine departments. Conclusion: The COVID‐19 pandemic has led to an overall reduction of blood transfusion activities in most cities in China, in particular blood donations and blood demands. [ABSTRACT FROM AUTHOR]

This study explores the use of in situ cross‐linked hyaluronic acid methacryloyl (HAMA) and hydroxyapatite particles (HAP) for bone defect repair. Human periodontal ligament stem cells (PDLSCs) were isolated and co‐cultured with the HAMA‐HAP composite. Osteogenic differentiation was evaluated using Alizarin Red staining, alkaline phosphatase activity quantification, and polymerase chain reaction (PCR). A cranial defect was induced in Sprague–Dawley rats. This defect was then filled with the HAMA‐HAP composite and cross‐linked using UV light exposure. Bone formation was assessed through radiographic and histological analyses. The HAMA‐HAP composite was found to promote cell viability similarly to pure HAP. It also enhanced gene expression of ALP, OPN, and Runx2, and increased ALP activity and mineralized nodule formation in vitro. Micro‐CT scans showed defect restoration in the HAMA‐HAP and HAP groups compared to the control group. The HAMA‐HAP group exhibited higher Tb.N, Tb.Sp, Tb.Th, and BV/TV. Masson staining showed the HAMA‐HAP composite restored the defect site, with new bone formation thicker than in the HAP group. The HAMA‐HAP composite showed excellent biocompatibility and promoted osteogenic differentiation of PDLSCs. It effectively repaired cranial defects, indicating its potential for clinical use in bone defect repair. [ABSTRACT FROM AUTHOR]

With the increased use of artificial light and the prolonged use of optoelectronic products, light damage (LD) to the human retina has been identified as a global vision‐threatening problem. While there is evidence of a significant correlation between light‐induced retinal damage and age‐related vision impairment in age‐related macular degeneration, it is unclear how light‐induced retinal degeneration manifests itself and whether there are agents capable of preventing the development of LD in the retina. This study investigated a mechanism by which blue light leads to photoreceptor death. By observing blue light exposure in retinal organoids and photoreceptor cells, we concluded that there could be significant apoptosis of the photoreceptors. We demonstrate that regenerating islet‐derived 1 alpha (REG1A) prevents photoreceptors from undergoing this LD‐induced apoptosis by increasing expression of the anti‐apoptotic gene Bcl2 and downregulating expression of the pro‐apoptotic gene Bax, resulting in reduced mitochondrial damage and improved aerobic capacity in photoreceptor cells. For the first time, REG1A has been shown to restore mitochondrial function and cell apoptosis after LD‐induced damage, suggesting its potential application in the prevention and treatment of retinal vision loss. [ABSTRACT FROM AUTHOR]

Single‐cell epigenetics is envisioned to decipher manifold epigenetic phenomena and to contribute to our accurate knowledge about basic epigenetic mechanisms. Engineered nanopipette technology has gained momentum in single‐cell studies; however, solutions to epigenetic questions remain unachieved. This study addresses the challenge by exploring N6‐methyladenine (m6A)‐bearing deoxyribozyme (DNAzyme) confined within a nanopipette for profiling a representative m6A‐modifying enzyme, fat mass and obesity‐associated protein (FTO). Electroosmotic intracellular extraction of FTO could remove the m6A and cause DNAzyme cleavage, leading to the altered ionic current signal. Because the cleavage can release a DNA sequence, we simultaneously program it as an antisense strand against FTO‐mRNA, intracellular injection of which has been shown to induce early stage apoptosis. This nanotool thus features the dual functions of studying single‐cell epigenetics and programmable gene regulation. [ABSTRACT FROM AUTHOR]

Construction of polymer‐based artificial solid‐electrolyte interphase films on Zn metal anode holds great potential in the suppression of both dendrite growth and side reaction in rechargeable aqueous Zn‐ion batteries. However, the traditional polymer films suffer from the critical issues of sluggish Zn2+ transport kinetics and rigid interface. Herein, zinc alginate (ZA) hydrogel is designed and prepared as a dynamic interface and Zn2+ redistributor on Zn anode via in situ cross‐linking reaction. The zincophilic and negatively charged carboxyl groups of ZA promote the transport of Zn2+ ions along a "Z‐type" pathway, the repulsion of free SO42‐ anions, and the desolvation of Zn2+ ions, consequently leading to the homogeneous deposition of Zn and the effective suppression of side reaction. Additionally, the dynamic flexibility of ZA hydrogel endows the Zn anode with self‐adapting interface to accommodate the volume variation and repair the possible ruptures, thereby guaranteeing the long‐term cycling stability. Assisted by the ZA layer, the Zn anode achieves a prolonged lifespan over 2200 h without the formation of Zn dendrites and by‐products. Outstanding cycling stability is also demonstrated for the Zn anode when coupled with MnO2 cathode, further demonstrating its prospects for practical application. [ABSTRACT FROM AUTHOR]

Aim: To investigate the interplay of incident chronic kidney disease (CKD) and/or heart failure (HF) and their associations with prognosis in a large, population‐based cohort with type 2 diabetes (T2DM). Methods: Patients aged ≥18 years with new‐onset T2DM, without renal disease or HF at baseline, were identified from the territory‐wide Clinical Data Analysis Reporting System between 2000 and 2015. Patients were followed up until December 31, 2020 for incident CKD and/or HF and all‐cause mortality. Results: Among 102 488 patients (median age 66 years, 45.7% women, median follow‐up 7.5 years), new‐onset CKD occurred in 14 798 patients (14.4%), in whom 21.7% had HF. In contrast, among 9258 patients (9.0%) with new‐onset HF, 34.6% had CKD. The median time from baseline to incident CKD or HF (4.4 vs. 4.1 years) did not differ. However, the median (interquartile range) time until incident HF after CKD diagnosis was 1.7 (0.5‐3.6) years and was 1.2 (0.2‐3.4) years for incident CKD after HF diagnosis (P < 0.001). The crude incidence of CKD was higher than that of HF: 17.6 (95% confidence interval [CI] 17.3‐17.9) vs. 10.6 (95% CI 10.4‐10.9)/1000 person‐years, respectively, but incident HF was associated with a higher adjusted‐mortality than incident CKD. The presence of either condition (vs. CKD/HF‐free status) was associated with a three‐fold hazard of death, whereas concomitant HF and CKD conferred a six to seven‐fold adjusted hazard of mortality. Conclusion: Cardiorenal complications are common and are associated with high mortality risk among patients with new‐onset T2DM. Close surveillance of these dual complications is crucial to reduce the burden of disease. [ABSTRACT FROM AUTHOR]

Single‐cell protein therapeutics is expected to promote our in‐depth understanding of how a specific protein with a therapeutic dosage treats the cell without population averaging. However, it has not yet been tackled by current single‐cell nanotools. We address this challenge by the use of a double‐barrel nanopipette, in which one lumen was used for electroosmotic cytosolic protein delivery and the other was customized for ionic evaluation of the consequence. Upon injection of protein DJ‐1 through the delivery lumen, upregulation of the antioxidant protein could protect neural PC‐12 cells against oxidative stress from phorbol myristate acetate exposure, as deduced by targeting of the cytosolic hydrogen peroxide by the detecting lumen. The nanotool developed in this study for single‐cell protein therapeutics provides a perspective for future single‐cell therapeutics involving different therapeutic modalities, such as peptides, enzymes and nucleic acids. [ABSTRACT FROM AUTHOR]

The harm of childhood parental neglect to emerging adults' maladjustment has garnered empirical support. For college students who have left‐behind experience (LBE), this relationship is rarely discussed and the psychological process underlying this relationship is not well understood. Using a longitudinal study and guided by the Risky Families model, this study aimed to explore the mediating roles of anxious attachment and perceived social support in the link between parental neglect and maladjustment of LBE college students. We used two‐wave longitudinal data, with a time lag of 3 months, collected among Chinese college students with LBE in Chongqing (N = 391). The results revealed that parental neglect in wave one was positively associated with maladjustment (depression, anxiety, and stress) in wave two. Anxious attachment and perceived social support in wave two separately mediated the relationship between parental neglect in wave one and maladjustment in wave two. Anxious attachment and perceived social support in wave two only sequentially mediated the pathway from parental neglect to later depression. These findings emphasize the importance of anxious attachment and social support in resilience and have significant implications for LBE college students' social work practice in China. [ABSTRACT FROM AUTHOR]

Background: To explore the prognosis predicting ability of the combined factors, Epstein–Barr virus DNA change level (EBVCL) and tumor volume reduction ratio (TVRR) after inductive chemotherapy (IC), in locally advanced nasopharyngeal carcinoma (LANPC). Methods: From 2010 to 2018, 299 LANPC patients were included in this retrospective study. Receiver operating characteristic (ROC) curve analysis was performed to acquire the best critical values. According to the best critical values of EBVCL and TVRR, patients were stratified into low‐ and high‐risk groups. Kaplan–Meier and ROC curve analyses were utilized to verify the prognostic ability of the new predictor (EBVCL+TVRR). The prognostic values among EBVCL+TVRR, EBVCL, TVRR, TNM stage, and the RECIST 1.1 criteria were compared by ROC curve. The primary end points were overall survival (OS), progression‐free survival (PFS), distant metastasis‐free survival (DMFS), and locoregional failure‐free survival (LRFFS). Results: ROC curve analyses of TVRR on three‐year survival showed the best critical values of TVRR was 32.72% for OS, 30.21% for PFS and LRFFS, 29.87% for DMFS. The best critical value of EBVCL was 127 copies/ml for OS, and 87.7 copies/ml for PFS, DMFS, and LRFFS. The three‐year OS, PFS, DMFS, and LRFFS for low‐ and high‐risk groups were 97.7% versus 78.3% (hazard ratio [HR] = 0.2398; 95% confidence interval [CI]: 0.1277–0.4502; p < 0.0001), 91.1% versus 60.9% (HR = 0.3294; 95% CI: 0.2050–0.5292; p < 0.0001), 94.2% versus 68.7% (HR = 0.2413; 95% CI: 0.1284–0.4535; p < 0.0001) and 97.8% versus 77.9% (HR = 0.3078; 95% CI: 0.1700–0.5573; p = 0.0001), respectively. The maximal area under ROC curve of EBVCL+TVRR, EBVCL, TVRR, TNM stage, and RECIST 1.1 criteria for three‐year OS was 0.829, 0.750, 0.711, 0.555, and 0.605, respectively. Conclusion: The new‐developed indicator (EBVCL+TVRR) could better predict the LANPC patient's survival after IC compared with TNM stage system or RECIST 1.1 criteria. [ABSTRACT FROM AUTHOR]

Objectives: The protective role of self‐compassion in emerging adult depression has garnered empirical support. It makes more sense to understand the psychological processes underlying this relationship. Based on the stress appraisal patterns, the present study examined the mediating roles of emotion regulation (ER) and resilience in the link between self‐compassion and depression among college students with left‐behind experience (LBE). Methods: A total of 391 LBE college students (Mage = 18.43 years; SD = 0.79 years) in Chongqing reported their demographic information and self‐compassion (the Self‐Compassion Scale) level at baseline (T1) and reported their levels of ER (the Emotion Regulation Scale), resilience (the Connor–Davidson Resilience Scale), and depression (the Depression‐Anxiety‐Stress Scale) 3 months later (T2). Results: The results revealed that (a) both ER (cognitive reappraisal and expressive suppression) and resilience separately mediated the association between self‐compassion and depression; (b) cognitive reappraisal and resilience sequentially mediated this association. Conclusions: These findings reveal the underlying mechanisms of the associations between self‐compassion and depression among LBE college students and have implications for interventions aimed at mitigating their depression. [ABSTRACT FROM AUTHOR]

Chiral oxindoles are important chemical scaffolds found in many natural products, and their enantioselective synthesis thus attracts considerable attention. Highly diastereo‐ and enantioselective synthetic methods for constructing C3 quaternary oxindoles have been well‐developed. However, the efficient synthesis of chiral 3‐substituted tertiary oxindoles has been rarely reported due to the ease of racemization of the tertiary stereocenter via enolization. Therefore, we herein report on the multicomponent assembly (from N‐aryl diazoamides, aldehydes, and enamines/indoles) of complex oxindoles by enantioselective cooperative catalysis. These reactions proceed under mild conditions and show broad substrate scope, affording the desired coupling products (>90 examples) with good to excellent stereocontrol. Additionally, this research also demonstrates the synthetic potential of this annulation by constructing the 6,6,5‐tricyclic lactone core structure of Speradine A. [ABSTRACT FROM AUTHOR]

Rational utilization of the rich light‐bio‐matter interplay taking place in single‐cell analysis represents a new technological direction in the field. The light‐fueled operation is expected to achieve advanced photoelectrochemical (PEC) single‐cell analysis with unknown possibilities. Here, a PEC nanoreactor capable of single‐cell sampling and near zero‐background Faradaic detection of intracellular microRNA (miR) is devised by the construction of a small reaction chamber accommodating the target‐triggered hybridization chain reaction for binding the metallointercalator of [Ru(bpy)2(dppz)]2+ as the signal reporter. Light stimulation of the dsDNA/metallointercalator adduct will induce the generation of photocurrents, underpinning a zero‐biased and near zero‐background PEC method toward Faradaic detection of non‐electrogenic miR at the single‐cell level. Using this nanotool, lower miR concentration in the near‐nucleus region than that in the main cytosol was revealed. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effects of exosomes derived from stem cells from the apical papilla (SCAP‐Exos) in rats with experimentally induced pulpitis and the effects of SCAP‐Exos on the conversion of regulatory T cells (Tregs) and methylation status of the Foxp3 locus in Tregs in vitro. Methodology: SCAP‐Exos were isolated and identified using transmission electron microscopy, western blotting, and nanoparticle tracking analysis. Lipopolysaccharide was used to experimentally induced pulpitis in rats, and the effects of SCAP‐Exos on the rats with pulpitis were detected using haematoxylin‐eosin staining and immunofluorescence staining. CD4+CD25‐ T cells were treated with different doses of SCAP‐Exos, and flow cytometric analysis was used to assess the effects of SCAP‐Exos on Treg proliferation and conversion. An enzyme‐linked immunosorbent assay (ELISA) was used to evaluate the expression of interleukin 10 (IL‐10). MethylTarget® technology was used to measure the methylation level of the Foxp3 locus in T cells. The expression levels of ten‐eleven‐translocation (Tet) 1, Tet2, and Tet3 in T cells were detected by real‐time PCR and western blotting. Results: SCAP‐Exos had an elliptical vesicle‐like structure with a diameter of approximately 143.7 nm and expressed the exosomal markers Alix and CD9. SCAP‐Exo administration increased Treg accumulation in the inflamed dental pulp and alleviated inflammation in the dental pulp in vivo. SCAP‐Exos promoted Treg conversion in vitro. Mechanistically, SCAP‐Exos promoted Tet2‐mediated Foxp3 demethylation to maintain the stable expression of Foxp3. Conclusions: SCAP‐Exos promoted Treg conversion and effectively alleviated inflammation in the dental pulp of rats. This study shows that SCAP‐Exos can regulate the local immune microenvironment to favour tissue regeneration, thus providing a potential novel strategy utilising SCAP‐Exos as a cell‐free approach to treat early inflammation of dental pulp in immature permanent teeth in the clinic. [ABSTRACT FROM AUTHOR]

With reduced background and high sensitivity, photoelectrochemistry (PEC) may be applied as an intracellular nanotool and open a new technological direction of single‐cell study. Nevertheless, the present palette of single‐cell tools lacks such a PEC‐oriented solution. Here a dual‐functional photocathodic single‐cell nanotool capable of direct electroosmotic intracellular drug delivery and evaluation of oxidative stress is devised by engineering a target‐specific organic molecule/NiO/Ni film at the tip of a nanopipette. Specifically, the organic molecule probe serves simultaneously as the biorecognition element and sensitizer to synergize with p‐type NiO. Upon intracellular delivery at picoliter level, the oxidative stress effect will cause structural change of the organic probe, switching its optical absorption and altering the cathodic response. This work has revealed the potential of PEC single‐cell nanotool and extended the boundary of current single‐cell electroanalysis. [ABSTRACT FROM AUTHOR]

American ginseng (AG), the underground part of Panax quinquefolium L., is composed of four morphological regions, including main root (MR), lateral root (LR), fibrous root (FR), and rhizome (RH). In the clinical, MR is the main medicinal region, other regions are rarely attention. Aiming at revealing the chemical composition of AG and making better use of AG, screening analysis and metabolomic analysis were both performed to profile MR, LR, FR, and RH. First, in the systematical screening analysis, a total of 134 compounds (including 122 shared components) with various structural patterns were identified and tentatively characterized. The results indicated that the phytochemicals with various structural types were rich in MR, LR, FR, and RH. Second, 6, 4, 8, and 11 chemical markers were identified from MR, LR, FR, and RH, respectively. Seven triterpene saponins (protopanaxatriol, quinquenoside R1, ginsenoside Rc, Rk1, Rg1, Re, and vinaginsenoside R1) might be used for rapid differentiation of four morphological regions. This comprehensive profile study of metabolites illustrated the similarities and differences of phytochemicals in four morphological regions of AG. The results could be used for the quality control of AG and furnish a basis for the further development and utilization of AG sources. [ABSTRACT FROM AUTHOR]

We aimed to establish a 1‐Deoxynojirimycin (DNJ) sustained‐release delivery system to improve the hypoglycemic effect of DNJ. We used a transdermal diffusion meter in an in vitro orthogonal experiment to determine the optimal composition of the DNJ sustained‐release transdermal system. Based on the in vitro analysis results, a sustained‐release patch was prepared, and its pharmacokinetics and other properties were determined in vivo. The results showed that 30% hydroxypropyl methylcellulose (K100M), 14% carboxymethyl cellulose sodium and 26% oleic acid‐azone compound as the matrix material, drug excipient, and penetration enhancer, respectively, produced an optimal DNJ sustained‐release delivery system. In vitro release tests showed that the system slowly released DNJ within 12 hr, conforming to the Higuchi equation. In vivo experiments showed that the prepared patch had good hypoglycemic activity and continuously released DNJ within 10 hr. In vivo pharmacokinetic study results showed that compared to conventional patches, the prepared patch exhibited significantly different maximum concentration (Cmax), time to achieve Cmax (Tmax), and area under the curve from 0 to time t (AUC[0‐t]) as well as improved pharmacokinetics. In conclusion, the prepared DNJ patch has high stability, a sustained‐release effect, and relatively good pharmacokinetics and is a safe dosage form that does not cause skin irritation. [ABSTRACT FROM AUTHOR]

Summary: A paradoxical result of using antibiotics to eradicate microbial pathogens is the emergence of a vast number of resistant microbes in various environments. The concern that environmental microbes will inevitably become resistant to virtually every clinically usable antibiotics has been exacerbated by the spread of these resistance genes across different environments and the emergence of multidrug resistant phenotypes. Here, we provide metagenomic insights into the microbiomes and resistomes of 16 soil samples collected from hospitals, residential areas, and forest parks in the megacity of Beijing and deep forests in the Yunnan province. Using Illumina HiSeq sequencing, we investigated the microbial diversity within the metagenomic shotgun reads and identified 486 antibiotic‐resistant genes (ARGs) classified into 30 types from these samples, among which multidrug resistance genes were the most abundant. Our results present an important reference and direct comparison of microbial antibiotic resistomes of soil samples from a megacity and deep forests and extend our understanding of the spread of ARGs in modern urban and natural environments. [ABSTRACT FROM AUTHOR]

Transposable elements exist widely throughout plant genomes and play important roles in plant evolution. Auxin is an important regulator that is traditionally associated with root development and drought stress adaptation. The DEEPER ROOTING 1 (DRO1) gene is a key component of rice drought avoidance. Here, we identified a transposon that acts as an autonomous auxin‐responsive promoter and its presence at specific genome positions conveys physiological adaptations related to drought avoidance. Rice varieties with a high and auxin‐mediated transcription of DRO1 in the root tip show deeper and longer root phenotypes and are thus better adapted to drought. The INDITTO2 transposon contains an auxin response element and displays auxin‐responsive promoter activity; it is thus able to convey auxin regulation of transcription to genes in its proximity. In the rice Acuce, which displays DRO1‐mediated drought adaptation, the INDITTO2 transposon was found to be inserted at the promoter region of the DRO1 locus. Transgenesis‐based insertion of the INDITTO2 transposon into the DRO1 promoter of the non‐adapted rice variety Nipponbare was sufficient to promote its drought avoidance. Our data identify an example of how transposons can act as promoters and convey hormonal regulation to nearby loci, improving plant fitness in response to different abiotic stresses. Role of auxin regulating drought avoidance remains unclear. In this study, an INDITTO2 transposon inserted at a DRO1 locus conveys auxin‐regulated transcription of the DRO1 and thus enhances rice root drought avoidance. It shows that the interaction of transposon and auxin can improve plant fitness. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to use a metabonomics approach to identify potential biomarkers of exhaled breath condensate (EBC) for predicting the prognosis of acute‐on‐chronic liver failure (ACLF). Methods: Using liquid chromatography mass spectrometry, EBC metabolites of ACLF patients surviving without liver transplantation (n = 57) and those with worse outcomes (n = 45), and controls (n = 15) were profiled from a specialized liver disease center in Beijing. The metabolites were used to identify candidate biomarkers, and the predicted performance of potential biomarkers was tested. Results: Forty‐one metabolites, involving glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, and amino acid metabolism, as candidate biomarkers for discriminating the different outcomes of ACLF were selected. A prognostic model was constructed by a panel of four metabolites including phosphatidylinositol [20:4(5Z,8Z,11Z,14Z)/13:0], phosphatidyl ethanolamine (12:0/22:0), L‐metanephrine and ethylbenzene, which could predict the worse prognosis in ACLF patients with sensitivity (84.4%) and specificity (89.5%) (area under the receiver operating characteristic curve [AUC] = 0.859, 95% confidence interval [CI] = 0.787–0.931). Compared with Model for End‐Stage Liver Disease (MELD) score (AUC = 0.639, 95% CI = 0.526–0.753) and MELD‐sodium (MELD‐Na) score (AUC = 0.692, 95% CI = 0.582–0.803), EBC‐associated metabolite signature model could better predict worse outcomes in patients with ACLF (p < 0.05). Using the MELD‐Na score and EBC metabolite signatures, a decision tree model was built for predicting the prognosis of ACLF identified on logistic regression analyses (AUC = 0.906, 95% CI = 0.846–0.965). Conclusion: EBC metabolic signatures show promise as potential biomarkers for predicting worse prognosis of ACLF. [ABSTRACT FROM AUTHOR]

The optimised droop control method is proposed to achieve the state‐of‐charge (SoC) balance among parallel‐connected distributed energy storage units in islanded DC microgrid, which considers the difference of line impedance, initial state‐of‐charge values and capacities among distributed energy storage units. Since the droop control is the basic control strategy for load sharing in DC microgrid applications, however, the load sharing accuracy is degraded under conventional droop control method due to the unmatched line impedance in reality. Meanwhile, the initial state‐of‐charge values and capacities of each distributed energy storage unit are usually different. Hence, the state of charge for distributed energy storage units cannot be balanced. In order to prolong the lifetime of the distributed energy storage units and avoid the overuse of a certain distributed energy storage unit, the optimised droop control strategy based on sample and holder is designed, by modifying the droop coefficient adaptively, the accurate load sharing and balanced state of charge among distributed energy storage units are both obtained. Finally, the performance of the proposed control scheme is accessed through a series cases on technologies real‐time digital simulator (RTDS) and its effectiveness is verified. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the human gastrointestinal tract. In this study, we performed single‐cell RNA sequencing (RNA‐seq) on intra‐ and peri‐tumor tissues from GIST patients with the aim of discovering the heterogeneity of tumor cells in GIST and their interactions with other cells. We found four predominating cell types in GIST tumor tissue, including T cells, macrophages, tumor cells, and NK cells. Tumor cells could be clustered into two groups: one was highly proliferating and associated with high risk of metastasis, the other seemed "resting" and associated with low risk. Their clinical relevance and prognostic values were confirmed by RNA‐seq of 65 GIST samples. T cells were the largest cell type in our single‐cell data. Two groups of CD8+ effector memory (EM) cells were in the highest clonal expansion and performed the highest cytotoxicity but were also the most exhausted among all T cells. A group of macrophages were found polarized to possess both M1 and M2 signatures, and increased along with tumor progression. Cell‐to‐cell interaction analysis revealed that adipose endothelial cells had high interactions with tumor cells to facilitate their progression. Macrophages were at the center of the tumor microenvironment, recruiting immune cells to the tumor site and having most interactions with both tumor and nontumor cells. In conclusion, we obtained an overview of the GIST microenvironment and revealed the heterogeneity of each cell type and their relevance to risk classifications, which provided a novel theoretical basis for learning and curing GISTs. [ABSTRACT FROM AUTHOR]

Background: Quite a few studies on anal functions after open total mesorectal excision combined with transanal intersphincteric resection (ISR) have been reported, but there is little literature on anal function after laparoscopic total mesorectal excision (LTME) combined with transanal ISR. The aim of this study was to explore the post‐operative anorectal dynamic changes in ultra‐low rectal cancer patients undergoing LTME combined with transanal ISR. Methods: The data of 26 ultra‐low rectal cancer patients undergoing LTME + transanal ISR were analysed. A total of 30 patients undergoing laparoscopic low anterior resection by the same surgeons during the same period were randomly enrolled into the control group. Results: There were no differences in the preoperative anorectal manometry data and Wexner anal function scores between the observation group and the control group (P > 0.05). There were no significant differences in the mean operation time, the mean amount of bleeding and the mean post‐operative hospital stay between the two groups (P > 0.05). The mean follow‐up time was 16 months. No recurrence and metastasis were found in all cases. At 3 and 6 months after the operation, there were significant differences in the anorectal manometry data and Wexner anal function scores between the two groups (P < 0.05). However, at 1 year after the operation, there were no significant differences in the anorectal manometry data and Wexner anal function scores between the two groups (P > 0.05). Conclusion: Laparoscopic ISR for ultra‐low rectal cancer is technically feasible, but the surgical indications should be strictly defined. [ABSTRACT FROM AUTHOR]

Background: Driveline infection (DLI) is the most common left ventricular assist device (LVAD) infectious complication. Short‐term antimicrobial therapy and local debridement are the cornerstones of management for these infections, but the use of chronic antimicrobial suppression (CAS) therapy is not well characterized. Methods: To better characterize the efficacy of CAS therapy, we performed a retrospective review of all patients (N = 219) receiving care at our tertiary transplant center with continuous‐flow LVADs placed between August 2007 and July 2019. Results: A total of 24 patients were identified as having received CAS therapy as treatment for DLIs. The mean age was 56 years, 50% were female, and chronic kidney disease affected 63% of patients. Staphylococcus aureus accounted for half of all initial DLIs, and the mean length of CAS therapy was 486 days (range 48‐2287 days). All patients received per os regimens as suppression therapy. Adverse events impacted 5 of 24 patients (0.43 events per 1000 days). Overall, the use of CAS therapy led to successful outcomes in 50% of patients and 29% experienced treatment failures. The remaining patients experienced stable symptoms. Relapses were the most common cause of treatment failure, and three patients experienced reinfections while on CAS therapy. Conclusions: Our study suggests that CAS therapy for DLIs can be well tolerated, and future studies are needed to determine which patients merit suppression. [ABSTRACT FROM AUTHOR]

Aims: Failure of neural tube closure resulting from excessive apoptosis leads to neural tube defects (NTDs). NADPH oxidase 4 (NOX4) is a critical mediator of cell growth and death, yet its role in NTDs has never been characterized. NOX4 is a potential target of miR‐322, and we have previously demonstrated that miR‐322 was involved in high glucose‐induced NTDs. In this study, we investigated the effect of NOX4 on the embryonic neuroepithelium in NTDs and reveal a new regulatory mechanism for miR‐322 that disrupts neurulation by ameliorating cell apoptosis. Methods: All‐trans‐retinoic acid (ATRA)‐induced mouse model was utilized to study NTDs. RNA pull‐down and dual‐luciferase reporter assays were used to confirm the interaction between NOX4 and miR‐322. In mouse neural stem cells and whole‐embryo culture, Western blot and TUNEL were carried out to investigate the effects of miR‐322 and NOX4 on neuroepithelium apoptosis in NTD formation. Results: NOX4, as a novel target of miR‐322, was upregulated in ATRA‐induced mouse model of NTDs. In mouse neural stem cells, the expression of NOX4 was inhibited by miR‐322; still further, NOX4‐triggered apoptosis was also suppressed by miR‐322. Moreover, in whole‐embryo culture, injection of the miR‐322 mimic into the amniotic cavity attenuated cell apoptosis in NTD formation by silencing NOX4. Conclusion: miR‐322/NOX4 plays a crucial role in apoptosis‐induced NTD formation, which may provide a new understanding of the mechanism of embryonic NTDs and a basis for potential therapeutic target against NTDs. [ABSTRACT FROM AUTHOR]

Serpinb6b is a novel member of Serpinb family and found in germ and somatic cells of mouse gonads, but its physiological function in uterine decidualization remains unclear. The present study revealed that abundant Serpinb6b was noted in decidual cells, and advanced the proliferation and differentiation of stromal cells, indicating a creative role of Serpinb6b in uterine decidualization. Further analysis found that Serpinb6b modulated the expression of Mmp2 and Mmp9. Meanwhile, Serpinb6b was identified as a target of Bmp2 regulation in stromal differentiation. Treatment with rBmp2 resulted in an accumulation of intracellular cAMP level whose function in this differentiation program was mediated by Serpinb6b. Addition of PKA inhibitor H89 impeded the Bmp2 induction of Serpinb6b, whereas 8‐Br‐cAMP rescued the defect of Serpinb6b expression elicited by Bmp2 knock‐down. Attenuation of Serpinb6b greatly reduced the induction of constitutive Wnt4 activation on stromal cell differentiation. By contrast, overexpression of Serpinb6b prevented this inhibition of differentiation process by Wnt4 siRNA. Moreover, blockage of Wnt4 abrogated the up‐regulation of cAMP on Serpinb6b. Collectively, Serpinb6b mediates uterine decidualization via Mmp2/9 in response to Bmp2/cAMP/PKA/Wnt4 pathway. [ABSTRACT FROM AUTHOR]

Genistein is an isoflavone that has estrogen (E2)‐like activity and is beneficial for follicular development, but little is known regarding its function in oxidative stress (OS)‐mediated granulosa cell (GC) injury. Here, we found that after exposure to H2O2, Genistein weakened the elevated levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA), which were regarded as the biomarkers for OS, and rescued glutathione (GSH) content and GSH/GSSG ratio accompanying with a simultaneous increase in cyclic adenosine monophosphate (cAMP) level, whereas addition of protein kinase A (PKA) inhibitor H89 impeded the effects of Genistein on the levels of ROS and MDA. Further analysis evidenced that Genistein enhanced the activities of antioxidant enzymes superoxide dismutase (SOD), GSH‐peroxidase (GSH‐Px), and catalase (CAT) in H2O2‐treated GCs, but this enhancement was attenuated by H89. Under OS, Genistein improved cell viability and lessened the apoptotic rate of GCs along with a reduction in the activity of Casp3 and levels of Bax and Bad messenger RNA (mRNA), while H89 reversed the above effects. Moreover, Genistein treatment caused an obvious elevation in mitochondrial membrane potential (MMP) followed by a decline in the levels of intracellular mitochondrial superoxide, but H89 inhibited the regulation of Genistein on MMP and mitochondrial superoxide. Supplementation of Genistein promoted the secretion of E2 and increased the expression of Star and Cyp19a1 mRNA, whereas suppressed the level of progesterone (P4) accompanied with a decline in the level of Hsd3b1 mRNA expression. H89 blocked the regulation of Genistein on the secretion of E2 and P4, and alleviated the ascending of Star and Cyp19a1 elicited by Genistein. Collectively, Genistein protects GCs from OS via cAMP‐PKA signaling. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?What are the potential therapeutic roles of ginsenoside Rb1 and hydroxysafflor yellow A (HSYA) in polycystic ovary syndrome (PCOS).What is the main finding and its importance?HSYA restored the oestrous cycles of PCOS mice, reduced follicular cysts in ovaries and rescued abnormal hormone secretion; ginsenoside Rb1 did not ameliorate the main symptoms of PCOS mice. HSYA alleviated oxidative stress along with an enhancement of antioxidant enzyme activity. This highlights a potential role of HSYA in PCOS therapy. Polycystic ovary syndrome (PCOS) is the most common endocrine disease resulting in female infertility. Hydroxysafflor yellow A (HSYA) and ginsenoside Rb1 have been shown to have antioxidant properties, but little is known about their impact in PCOS. Here dehydroepiandrosterone was used to induce PCOS in a mouse model that was characterized by an irregular oestrous cycle, cystic follicles and an elevated serum testosterone level. Supplementation of HSYA restored the oestrous cycle of PCOS mice, reduced follicular cysts in PCOS mouse ovaries and brought about a decline in serum testosterone level, while ginsenoside Rb1 did not ameliorate the above symptoms of PCOS mice. After HSYA treatment, there was elevation of serum oestradiol, progesterone, luteinizing hormone and anti‐Müllerian hormone levels and a reduction of follicle‐stimulating hormone level, but ginsenoside Rb1 only rescued the levels of follicle‐stimulating hormone and anti‐Müllerian hormone. Further analysis evidenced that HSYA reversed the expression of steroid hormone secretion‐related genes Star, Hsd3b1, Cyp11a1 and Cyp19a1. In PCOS mice HSYA weakened the elevation of ovarian malondialdehyde, which is regarded as a biomarker for oxidative stress. Moreover, HSYA improved reduced glutathione content accompanied by a simultaneous increase in reduced to oxidized glutathione ratio, and enhanced the activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase. Collectively, HSYA exerted beneficial effects on PCOS mice by restoring hormone secretion and alleviating oxidative stress. [ABSTRACT FROM AUTHOR]

Objective: Neutrophil infiltration in patients with sinonasal inverted papilloma (SNIP) is significantly high. Whether IL‐17, which is a potent factor mediating neutrophilic inflammation, is involved in the neutrophilic phenotype of SNIP is investigated in the current study. Study design: Laboratorial study. Participants: Nasal papilloma and inferior turbinate were collected from patients with SNIP (n = 50) and control subjects with septal deviation (n = 15). Methods: IL‐17 + cells were evaluated in tissues obtained from patients with SNIP and control subjects with septal deviation, by immunohistochemistry and flow cytometry. Main outcome measures: The IL‐17 + cells were mainly localised in mononuclear cells and neutrophils, and were up‐regulated in the SNIP samples compared with those in the controls. The IL‐17 + T‐cell subsets mainly included CD4+ (Th17, 60.0%) and CD8+ (Tc17, 30.0%), and both subsets were enhanced in the SNIP samples than controls. The total level of IL‐17 + cells was significantly correlated with neutrophil infiltration in the SNIP tissues. Furthermore, the SNIP homogenates could significantly promote IL‐17 production in peripheral blood mononuclear cells. Conclusions: An increase in IL‐17 + cells is evident in SNIP and may be involved in neutrophil infiltration in local tissues. IL‐17 could be a potential therapeutic target to relieve the neutrophilic pathological change in SNIP. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is the six most common malignancy worldwide leading to more than 350,000 deaths annually. Despite recent advances in treatment modalities for these patients, there has been only a slight improvement of prognosis. As cancer stem cells (CSCs) have been implicated in tumor cell survival, progression, and response to therapy, the identification of this tumor subpopulation would have important therapeutic and prognostic implications. In this structured appraisal of the literature, Embase, PubMed, and Ovid were searched for publications that investigated CSC markers of HNC in humans. The search was conducted under the PRISMA guidelines with clear inclusion and exclusion criteria for articles published in the last two decades. The review process resulted in the identification of some key CSC‐associated molecules such as CD44, ALDH1, CD133, Oct3/4, Nanog, and Sox2, although a single common CSC sorting marker could not be found. These biomarkers were identified in a range of HNCs but the most common one was squamous cell carcinoma (SCC), predominantly oral SCC. Patient cohorts were of variable size (3–195 individuals) and the most common technique used for detection was immunohistochemistry. Some of the molecules were associated with poor prognosis and may be able to inform the choice of appropriate treatment for these patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Microbial dysbiosis is involved in the development of colorectal cancer and its most common precancerous lesion, colorectal adenoma. Endoscopic resection is one of the procedures for primary prevention of colorectal cancer, yet little is known about how the endoscopic therapy influences gut microbiota. Methods: We conducted a prospective study of 20 patients who underwent endoscopic resection of colorectal adenoma and analyzed the fecal microbiota before and 3 months after adenoma resection. MiSeq sequencing of 16S rRNA genes was performed to determine the alterations in microbial diversity and structure. To discriminate the microbiota of the two groups, random forest and receiver operating characteristic analysis were applied, and a genus‐based microbiota signature was obtained. Results: Despite few alterations in overall microbial structure after adenoma resection, the abundance of Parabacteroides revealed a significant increase postoperatively (3.8% vs 1.5%, 0.1160), and the microbiota signature of Parabacteroides, Streptococcus, and Ruminococcus showed an optimal discriminating performance of postoperative status with the area under the curve 0.788, P < 0.001. Conclusion: Fecal microbial alterations indicate the moderate influence of adenoma resection on gut microbiota and lay the groundwork for microbial prediction of adenoma recurrence. Larger sample studies are further required to validate the findings. [ABSTRACT FROM AUTHOR]

Transforming growth factor‐β (TGF‐β) and heat shock protein 70 (HSP70) are important for the hair follicle (HF) cycle, but it is unclear whether they participate in HF regression in yak skin. In this study, we investigated the role of TGF‐β, TGF‐βRII, and HSP70 in the transition from anagen to catagen of HFs. The results showed that TGF‐β2 transcription was significantly higher than that of TGF‐β1 and TGF‐β3 in the same periods. Meanwhile, the expressions of TGF‐β2, TGF‐βRII, and caspase‐3 were higher in the catagen phase than that in mid‐anagen, and some TGF‐βRII‐positive HF cells were terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate‐biotin nick end labeling (TUNEL)‐positive. Moreover, the HSP70 protein levels in mid‐anagen were higher than those in late‐anagen and catagen. These results suggested that TGF‐β2 plays a major role in catagen induction in yak HFs, which might be achieved via TGF‐βRII‐mediated apoptosis in HF epithelial cells. In contrast, HSP70 might protect epithelial cells from apoptosis and ultimately inhibit HF regression. In conclusion, TGF‐β2 has positive effects, whereas HSP70 has negative effects, on catagen induction. [ABSTRACT FROM AUTHOR]

Our previous studies showed that the transcription factor early growth response‐1 (EGR1) may play a role in keeping the brain cholinergic function intact in the preclinical stages of Alzheimer's disease (AD). In order to elucidate the mechanisms involved, we first performed data mining on our previous microarray study on postmortem human prefrontal cortex (PFC) for the changes in the expression of EGR1 and acetylcholinesterase (AChE) and the relationship between them during the course of AD. The study contained 49 patients, ranging from non‐demented controls (Braak stage 0) to late AD patients (Braak stage VI). We found EGR1‐mRNA was high in early AD and decreased in late AD stages, while AChE‐mRNA was stable in preclinical AD and slightly decreased in late AD stages. A significant positive correlation was found between the mRNA levels of these two molecules. In addition, we studied the relationship between EGR1 and AChE mRNA levels in the frontal cortex of 3–12‐months old triple‐transgenic AD (3xTg‐AD) mice. EGR1‐ and AChE‐mRNA were lower in 3xTg‐AD mice compared with wild‐type (WT) mice. A significant positive correlation between these two molecules was present in the entire group and in each age group of either WT or 3xTg‐AD mice. Subsequently, AChE expression was determined following up‐ or down‐regulating EGR1 in cell lines and the EGR1 levels were found to regulate AChE at both the mRNA and protein levels. Dual‐luciferase assay and electrophoretic mobility shift assay in the EGR1‐overexpressing cells were performed to determine the functionally effective binding sites of the EGR1 on the AChE gene promoter. We conclude that the EGR1 can upregulate AChE expression by a direct effect on its gene promoter, which may contribute significantly to the changes in cholinergic function in the course of AD. The 3xTg‐AD mouse model only reflects later stage AD. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that p62/SQSTM1 functions as a signalling centre in cancer. However, the role of p62 in tumour development depends on the interacting factors it recruits and its precise regulatory mechanism remains unclear. In this study, we investigated the pro‐death signalling recruitment of p62 with the goal of improving anti‐tumour drug effects in ovarian cancer treatment. We found that p62 with Caspase 8 high expression is correlated with longer survival time compared with cases of low Caspase 8 expression in ovarian cancer. In vivo experiments suggested that insoluble p62 and ubiquitinated protein accumulation induced by autophagy impairment promoted the activation of Caspase 8 and increased cell sensitivity to cisplatin. Furthermore, p62 functional domain UBA and LIR mutants regulated autophagic flux and attenuated Caspase 8 activation, which indicates that autophagic degradation is involved in p62‐mediated activation of Caspase 8 in ovarian cancer cells. Collectively, our study demonstrates that p62 promotes Caspase 8 activation through autophagy flux blockage with cisplatin treatment. We have provided evidence that autophagy induction followed by its blockade increases cell sensitivity to chemotherapy which is dependent on p62‐Caspase 8 mediated apoptosis signalling. p62 exhibits pro‐death functions through its interaction with Caspase 8. p62 and Caspase 8 may become novel prognostic biomarkers and oncotargets for ovarian cancer treatment. [ABSTRACT FROM AUTHOR]

A modelling and stability analysis method of a virtual synchronous machine (VSM) is proposed in this study. VSM technology is used to solve the problems caused by the high permeability of distributed energy. Though VSM has inertia and damping characteristics, it is more prone to oscillate than a synchronous generator because of the characteristic and unexpected harmonics generated by power electronic elements. The traditional linear time invariant based model is difficult to analyse a time-variant system and cannot analyse harmonic coupling mechanism accurately. This study proposes a new model of a grid-connected VSM by using the harmonic state-space modelling approach, which is a typical linear time-varying periodic model and considers different harmonics of the system. The stability of the system is analysed by eigenvalues of system matrix, which is based on the harmonic state-space model. The theoretical modelling method and stability analysis are verified by direct time-domain simulation results. [ABSTRACT FROM AUTHOR]

Background & Aims: Resistance to EGFR‐targeted therapy is a major obstacle in hepatocellular carcinoma (HCC) treatment, but its underlying mechanism remains unclear. Autophagy plays a vital role in antitumour treatment. Our previous study suggested that p57 is associated with autophagy and cisplatin resistance. The present study aimed to investigate whether p57 can enhance the sensitivity of HCC cells to Erlotinib (Er)/Cetuximab(C‐225) and further explore the potential mechanisms of Er/C‐225 resistance. Methods: HCC cells were transfected with pIRES2‐EGFP‐p57 and pIRES2‐EGFP‐nc, accompanied by Er/C‐225 treatment. Cell viability was detected by an Annexin apoptosis kit and MTT assay. Xenograft experiments were performed to study the function of p57 in the treatment of Er/C‐225 in vivo. The level of autophagy was determined by analysis of the appearance of autophagic vacuoles. Western blotting was used to investigate the potential pathways involved. Results: Up‐regulation of p57 decreased the level of Er/C‐225‐induced autophagy and enhanced the decrease in Er/C‐225‐induced cell viability. P57 overexpression combined with CQ treatment further enhanced the therapeutic efficiency of Er/C‐225. The xenograft experiment verified that p57 up‐regulation sensitizes HCC cells to Er/C‐225. Moreover, a mechanistic investigation demonstrated that the up‐regulation of p57 resulted in a decrease of LC3B‐II and beclin‐1, and an increase in p‐PI3K, p‐AKT and p‐mTOR protein expressions. Conclusions: Through activating the PI3K/AKT/mTOR signalling pathway, p57 can reverse Er/C‐225‐induced autophagy, and thereby increase the therapeutic efficiency of Er/C‐225 treatment. Given these results, p57 up‐regulation may be applicable as a therapeutic strategy to improve EGFR‐targeted therapy in HCC. [ABSTRACT FROM AUTHOR]