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Eltrombopag was approved as a first‐line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non‐severe AA (NSAA), are limited. We performed a prospective, single‐arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA). The efficacy and safety were assessed every 3 months. The population pharmacokinetic (PPK) model was used to depict the pharmacokinetic profile of eltrombopag. Twenty‐three AA children with an average age of 7.9 (range of 3.0‐14.0) years were enrolled. The response (complete and partial response) rate was 12.5%, 50.0%, and 100.0% after 3, 6, and 12 months in patients with NSAA. For patients with SAA and VSAA, these response rates were 46.7%, 61.5%, and 87.5%. Hepatotoxicity occurred in one patient. Fifty‐three blood samples were used to build the PPK model. Body weight was the only covariate for apparent clearance (CL/F) and volume of distribution. The allele‐T carrier of adenosine triphosphate‐binding cassette transporter G2 was found to increase eltrombopag's clearance. However, when normalized by weight, the clearance between the wild‐type and variant showed no statistical difference. In patients with response, children with NSAA exhibited lower area under the curve from time zero to infinity, higher CL/F, and higher weight‐adjusted CL/F than those with SAA or VSAA. However, the differences were not statistically significant. The results may support further individualized treatment of eltrombopag in children with AA. [ABSTRACT FROM AUTHOR]

Attracting pollinators to achieve successful reproduction is a key challenge for wild plants that may be disturbed by complex multispecies interactions in nature. Pairwise plant–pollinator interactions have traditionally been studied for decades, while ignoring other ecological players may obscure a comprehensive understanding on how plants recruit partners or combat enemies in the pollination process. Hence, integrated studies considering the inherent complexity of ecological interactions are needed, which may open up new perspectives for deciphering intricate systems and predicting ecological consequences.We examined the presence of nectar yeasts using a combination of high‐throughput sequencing, cultivation and microscopy and quantified floral herbivory by evaluating the incidence of flowers with visible holes in 13 natural populations of Iris bulleyana in the Hengduan Mountains of southwest China during 2017–2022. We combined yeast inoculation and herbivore manipulation treatments to illustrate the isolated and combined impacts of two contrasting nectarivorous organisms, the ascomycetous yeast Metschnikowia reukaufii and adult sawflies, on pollinator visitation and plant reproductive success in two populations. In the lab, we first employed gas chromatography–mass spectrometry to profile the volatile metabolites of yeast‐inoculated nectar relative to control, followed by a behavioural bioassay to test the preference of honeybees for these microbial volatiles.Yeasts commonly inhabited floral nectar and insect herbivores frequently bit holes in the perianth tube to consume nectar and nectaries. Nectar yeasts indirectly facilitated plant reproduction through increased pollinator visits, probably because of microbial metabolism as honeybees preferred nectar volatiles produced by yeasts in behavioural bioassays. Insect herbivores increased total floral visits but reduced legitimate visits by inducing legitimate‐to‐robbing behavioural changes of honeybees, thus leading to lower seed production. The detrimental effect of herbivory was mitigated by the presence of yeasts, which diminished the relative proportion of robbing visits and thereby 'rescued' flowers from reproductive failure.Synthesis: Overall, we found contrasting effects of non‐pollinator species, including both micro‐ and macro‐organisms, on plant–pollinator interactions in a biodiversity hotspot, where pollination deficit may be a ubiquitous phenomenon. Our findings suggest that both microbial and herbivory effects are likely to be important in explaining the exact causes of pollen limitation in species‐rich areas, highlighting the biological context dependence of species interactions in natural ecosystems. [ABSTRACT FROM AUTHOR]

Photochemical internalization is an efficient strategy relying on photodynamic reactions to promote siRNA endosomal escape for the success of RNA‐interference gene regulation, which makes gene‐photodynamic combined therapy highly synergistic and efficient. However, it is still desired to explore capable carriers to improve the delivery efficiency of the immiscible siRNA and organic photosensitizers simultaneously. Herein, we employ a micellar nanostructure (PSNA) self‐assembled from polymer‐DNA molecular chimeras to fulfill this task. PSNA can plentifully load photosensitizers in its hydrophobic core simply by the nanoprecipitation method. Moreover, it can organize siRNA self‐assembly by the densely packed DNA shell, which leads to a higher loading capacity than the typical electrostatic condensation method. The experimental results prove that this PSNA carrier can greatly facilitate siRNA escape from the endosome/lysosome and enhance transfection. Accordingly, the PSNA‐administrated therapy exhibits a significantly improved anti‐tumor efficacy owing to the highly efficient co‐delivery capability. [ABSTRACT FROM AUTHOR]

A meta‐analysis was executed to comprehensively examine the impacts of enhanced recovery after surgery (ERAS) care interventions on complications and wound infections following bladder cancer (BCa) surgery. Computer searches were carried out in Embase, Google Scholar, Cochrane Library, PubMed, Wanfang and CNKI, from their inception to November 2023, for RCTs regarding perioperative ERAS nursing interventions in patients with BCa. Two independent researchers performed literature screening, extracted data and carried out quality evaluations. Stata 17.0 software was utilized for the analysis of the data. Ultimately, 16 RCTs, involving 1190 patients, were included. The analysis showed that, in comparison with conventional nursing methods, perioperative ERAS nursing application in patients with BCa remarkably decreased the occurrence of wound infections (OR: 0.31, 95% CI: 0.16–0.59) and complications (OR: 0.19, 95% CI: 0.13–0.28). Our study indicates that perioperative care based on the ERAS concept remarkably decreased the occurrence of wound infections and complications following BCa surgery, demonstrating notable nursing efficacy and meriting widespread clinical promotion. [ABSTRACT FROM AUTHOR]

Deep NIR organic phototheranostic molecules generally have large π‐conjugation structures and show highly hydrophobic properties, thus, forming strong π–π stacking in the aqueous medium, which will affect the phototheranostic performance. Herein, an end‐group strategy is developed to lift the performance of NIR‐II emitting photosensitizers. Extensive characterizations reveal that the hydrogen‐bonding interactions of the hydroxyl end group can induce a more intense π–π electronic coupling than the chlorination‐mediated intermolecular forces. The results disclose that π–π stacking will lower fluorescence quantum yield but significantly benefit the photodynamic therapy (PDT) efficiency. Accordingly, an asymmetrically substituted derivative (BTIC‐δOH‐2Cl) is developed, which shows balanced phototheranostic properties with excellent PDT efficiency (14.6 folds of ICG) and high NIR‐II fluorescence yield (2.27%). It proves the validity of the end‐group strategy on controlling the π–π interactions and rational tuning the performance of NIR‐II organic phototheranostic agents. [ABSTRACT FROM AUTHOR]

Continuous 6‐mercaptopurine (6‐MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose‐limiting hematopoietic toxicity. However, evidence‐based guidelines for gene‐based 6‐MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open‐label, active‐controlled clinical trial randomly assigned Chinese children with low‐ or intermediate‐risk ALL in a 1:1 ratio to receive TPMT–NUDT15 gene–based dosing of 6‐MP (N = 44, 10 to 50 mg/m2/day) or standard dosing (N = 44, 50 mg/m2/day) during maintenance therapy. The primary end point was the incidence of 6‐MP myelosuppression in both groups. Secondary end points included frequencies of 6‐MP hepatotoxicity, duration of myelosuppression and leukopenia, event‐free survival, and steady‐state concentrations of active metabolites (6‐thioguaninenucleotides and 6‐methylmercaptopurine nucleotides) in erythrocytes. A 2.2‐fold decrease in myelosuppression, the primary end point, was observed in the gene‐based–dose group using ~ 50% of the standard initial 6‐MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene‐based–dose group had a significantly lower risk of developing thiopurine‐induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady‐state concentrations of active metabolites in erythrocytes between the two groups. TPMT‐ and NUDT15‐based dosing of 6‐MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393. [ABSTRACT FROM AUTHOR]

The essential branched‐chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs' full effects on mammalian physiology remain uncertain due to the complexities of BCAA metabolic regulation. Here a novel mechanism linking intrinsic alterations in BCAA metabolism is identified to cellular senescence and the senescence‐associated secretory phenotype (SASP), both of which contribute to organismal aging and inflammation‐related diseases. Altered BCAA metabolism driving the SASP is mediated by robust activation of the BCAA transporters Solute Carrier Family 6 Members 14 and 15 as well as downregulation of the catabolic enzyme BCAA transaminase 1 during onset of cellular senescence, leading to highly elevated intracellular BCAA levels in senescent cells. This, in turn, activates the mammalian target of rapamycin complex 1 (mTORC1) to establish the full SASP program. Transgenic Drosophila models further indicate that orthologous BCAA regulators are involved in the induction of cellular senescence and age‐related phenotypes in flies, suggesting evolutionary conservation of this metabolic pathway during aging. Finally, experimentally blocking BCAA accumulation attenuates the inflammatory response in a mouse senescence model, highlighting the therapeutic potential of modulating BCAA metabolism for the treatment of age‐related and inflammatory diseases. [ABSTRACT FROM AUTHOR]

To investigate the effects of long intergenic noncoding RNA‐erythroid prosurvival (lincRNA‐EPS) on periodontal inflammation mediated by inflammasomes and to explore its mechanism. Experimental periodontitis was induced in KO (lincRNA‐EPS−/−) and WT (lincRNA‐EPS+/+) mice to compare the periodontal bone loss and inflammation by using micro‐computed tomography, immunofluorescence staining and haematoxylin and eosin staining. The expression and activation of cysteinyl aspartate‐specific proteinase‐11 (caspase‐11) and NOD‐like receptor protein 3 (NLRP3) inflammasomes, as well as nuclear factor‐kappa B (NF‐κB) activation in mouse gingival fibroblasts (MGFs), were measured by real‐time quantitative polymerase chain reaction, Western blotting, enzyme‐linked immunosorbent and lactate dehydrogenase assays. MGFs were transfected with overexpression plasmids to assess the biological functions of lincRNA‐EPS. RNA pull‐down and immunoprecipitation experiments were performed to identify the interacting protein of lincRNA‐EPS. LincRNA‐EPS‐expressing lentivirus was locally administered to inflamed periodontal tissues to evaluate its salvage function in periodontitis. The absence of lincRNA‐EPS increased bone loss and expression of myeloperoxidase, interleukin‐1α (IL‐1α) and IL‐1β in the inflammatory periodontium. LincRNA‐EPS KO MGFs exhibited increased expression and activation of caspase‐11/NLRP3 inflammasome components than WT MGFs under lipopolysaccharide (LPS) stimulation. The expression and activation of these molecules were inhibited in lincRNA‐EPS overexpressed MGFs. Mechanistically, lincRNA‐EPS directly bound to transactive response DNA‐binding protein 43 (TDP43) in the nucleus of MGFs, and TDP43 knockdown exerted a similar inhibitory effect on NF‐κB activation and the inflammasomes as lincRNA‐EPS overexpression. Locally injecting lincRNA‐EPS‐expressing lentivirus weakened the periodontal damage. LincRNA‐EPS inhibits the LPS‐induced production and activation of caspase‐11 and NLRP3 inflammasomes by suppressing the activation of the NF‐κB signalling pathway via interacting with TDP43, thereby alleviating periodontitis. [ABSTRACT FROM AUTHOR]

Consistent hyperglycaemia on retinal microvascular tissues is recognized as a vital inducer of diabetic retinopathy (DR) pathogenesis. In view of the essential functionality of long noncoding RNAs (lncRNAs) in multiple human diseases, we aim to figure out the exact role and underlying mechanisms of lncRNA HOXD Cluster Antisense RNA 1 (HAGLR) in DR pathogenesis. Serum specimens from patients with proliferative DR and healthy volunteers were collected for measuring HAGLR levels. Human primary retinal pigment epithelium (HRPE) cells kept in high glucose (HG) condition were applied to simulating hyperglycaemia of DR pathology in vitro. Cell proliferation, apoptosis, either pyroptosis was assess using Cell Counting Kit‐8 TUNEL, flow cytometry, and enzyme‐linked immunoassay assays. Bioinformatics analysis was subjected to examine the interaction between HAGLR and N6‐methyladenosine (m6A)‐bind protein IGF2BP2, as determined using RNA immunoprecipitation and RNA pull‐down. Luciferase reporter assay was performed to assess the HAGLR‐miR‐106b‐5p‐PTEN axis. Levels of pyroptosis‐associated biomarkers were detected using western blotting. Aberrantly overexpressed HAGLR was uncovered in the serum samples of DR patients and HG‐induced HRPE cells, of which knockdown attenuated HG‐induced cytotoxic impacts on cell apoptosis and pyroptosis. Whereas, reinforced HAGLR further aggravated these effects. IGF2BP2 positively regulated HAGLR in a m6A‐dependent manner. HAGLR served as a sponge for miR‐106b‐5p to upregulate PTEN, thereby activating Akt signaling cascade. Rescue assays demonstrated that PTEN overexpression abolished the inhibition of silenced HAGLR on pyroptosis in HRPE cells. HAGLR, epigenetically modified by IGF2BP2 in an m6A‐dependent manner, functioned as a sponge for miR‐106b‐5p, thereby activating PTEN/Akt signaling cascade to accelerate DR pathology. [ABSTRACT FROM AUTHOR]

Aims: The aims of this systematic review were to obtain a comprehensive understanding of healthcare workers' experiences who were subjected to workplace violence in the home care environment and identify their specific support needs. Background: Workplace violence toward healthcare workers has been a prevalent and ongoing issue. With the expansion of home care services, more emphasis should be placed on maintaining a safe in‐home care environment for healthcare workers. Understanding healthcare workers' experience of workplace violence is crucial for developing effective interventions. Methods: A systematic search was conducted in 10 databases from their inception date until January 2022. Primary qualitative studies were included. Two reviewers performed screening of studies, methodological quality assessment, and data extraction and analysis independently. The two‐step approach by Sandelowski and Barroso on meta‐summary and meta‐synthesis was used. This qualitative systematic review was reported according to the PRISMA guidelines. Results: Eight studies were included. Three themes were identified: (1) impact of workplace violence, (2) reasons behind tolerating violence, and (3) way forward to prevent violence. Conclusion: Workplace violence is common among healthcare workers in home care settings, yet the support provided to healthcare workers is inadequate. The findings suggest the need for effective interventions and policies to address this grave issue in order to improve the well‐being of healthcare workers as it may indirectly affect the care quality provided to patients. Implications for nursing: Due to the unique nature of home care services, interventions preventing workplace violence must be tailored to the specific home care settings and needs of healthcare workers. Future research should develop and evaluate different interventions to prevent workplace violence in home care settings. [ABSTRACT FROM AUTHOR]

Chronic social isolation (SI) stress, which became more prevalent during the COVID‐19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti‐inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three‐week‐old male mice were randomly housed for 8 weeks in either group housing (GH) or SI. The animals were divided into normal saline‐treated GH, normal saline‐treated SI, and betaine‐treated SI groups in the sixth week. The cognitive and depression‐like behavior was determined in the eighth week. We found that long‐term betaine administration improved cognitive behavior in SI mice but failed to prevent depression‐like behavior. Moreover, long‐term betaine administration inhibited hippocampal microglia over‐activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic–pituitary–adrenal axis. Collectively, our findings reveal that betaine can improve SI‐induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron harbors more than 30 mutations of the spike protein and exhibits substantial immune evasion. Although previous study indicated that BNT162b2 messenger RNA vaccine induces potent cross‐clade pan‐sarbecovirus neutralizing antibodies in survivors of the infection by SARS‐CoV‐1, the neutralization activity and Fc‐mediated effector functions of these cross‐reactive antibodies elicited in SARS‐CoV‐1 survivors to Omicron subvariants still remain largely unknown. In this study, the neutralization activity and Fc‐mediated effector functions of antibodies boosted by a third dose vaccination were characterized in SARS‐CoV‐1 convalescents and healthy individuals. Potent cross‐clade broadly neutralizing antibodies were observed in SARS‐CoV‐1 survivors who received a three‐dose vaccination regimen consisting of two priming doses of CoronaVac followed by one booster dose of the protein subunit vaccine ZF2001. However, the induced antibodies exhibited both reduced neutralization and impaired Fc effector functions targeting multiple Omicron subvariants. Importantly, the data also support the notion that immune imprints resulted from SARS‐CoV‐1 infection may exacerbate the impairment of neutralization activity and Fc‐mediated effector functions to Omicron subvariants and provided invaluable information to vaccination strategy in future. [ABSTRACT FROM AUTHOR]

The Central Asian Orogenic Belt (CAOB) is the most significant accretionary orogenic belt since the Phanerozoic and the most ideal site for studying continental growth evolution processes. A 460‐km‐long high‐resolution crustal‐scale seismic reflection study was conducted across the eastern CAOB in North‐Central China to constrain the closure mode and location of the Paleo‐Asian Ocean, that is, the previous ocean of the CAOB. The resultant seismic reflection profile revealed opposite‐dipping reflectors in the northern and southern parts of the profile, which converge at the profile center to form an inverted U‐shaped reflector pattern near the crust–mantle transition zone beneath the Solonker Suture. The dipping reflectors represent bidirectional fossil subduction zones sloping to the north and south, and the convergence reflector pattern represents the ocean closure location. Integration of these results with available geological data facilitated model construction whereby Paleo‐Asian Ocean closure was accomplished by divergent subduction of the Paleo‐Asian oceanic plate, with northward subduction beneath the southern margin of the Mongolian Block and southward subduction beneath the northern margin of the North China Craton. The oceanic lithosphere contracted and deformed, yielding the observed inverted U‐shaped reflector pattern, representing Paleo‐Asian Ocean closure. This subsurface location lies beneath the Solonker Suture surface exposure, suggesting that this suture marks the ocean closure location, rather than the previously proposed Hegenshan–Heihe Suture to the north or Xar Moron Suture to the south. Our study suggests that divergently dipping subduction and associated accretion and magmatism may constitute the primary continental growth mode for accretionary‐type orogens. Plain Language Summary: The Central Asian Orogenic Belt (CAOB) is Earth's largest Phanerozoic accretionary orogenic belt, but its tectonic history remains uncertain, including the Paleo‐Asian Ocean closure location and mode. Here, we present a 460‐km‐long crustal‐scale seismic reflection survey across the eastern CAOB. According to the generated seismic profile, near‐symmetrical north‐ and south‐dipping reflectors occur in the crust–mantle transition zone, which are interpreted combined with published geological data to reveal that the Paleo‐Asian oceanic plate underwent divergent subduction beneath the South Mongolian Block and North China Craton. The inferred Paleo‐Asian Ocean closure location, the Solonker Suture, is identified by converging seismic reflectors in the central part of the profile. During oceanic subduction, newly formed accretionary complexes experienced soft collision with preexisting continental fragments. Therefore, we suggest that the eastern CAOB mainly comprises Paleozoic accretionary complexes with incorporated Precambrian fragments. We consider that divergently dipping oceanic subduction and associated accretion and magmatism constitute the main mode of CAOB continental growth and possibly of accretionary orogenic belts in general. Key Points: A crustal‐scale seismic profile reveals that the Paleo‐Asian Ocean was closed by double‐dipping subduction in the eastern Central Asian Orogenic BeltThe closure location of the ocean occurs between the Xar Moron and Hegenshan–Heihe sutures and extends eastward to central SongliaoOceanic double‐dipping subduction–accretion and magmatism are important mechanisms for accretionary orogens [ABSTRACT FROM AUTHOR]

Background: Lung cancer, especially non‐small cell lung cancer (NSCLC), is one of the leading causes of cancer‐related deaths worldwide. Vincristine (VCR) is a chemotherapeutic agent for lung cancers; however, its effectiveness is limited by side effects and the development of drug resistance. Patchouli alcohol (PA), from Pogostemon cablin extract, is known to possess anti‐inflammatory and anticancer properties. In this study, we investigated the role of PA in inducing reactive oxygen species (ROS)‐mediated DNA damage in A549 and VCR‐resistant A549/V16 NSCLC cells. Methods: The anticancer potential of PA was studied using the MTT assay, colony formation, flow cytometry analysis, western blotting, DCFDA staining, immunofluorescence staining, and TUNEL assay techniques. Results: The intracellular ROS levels were enhanced in PA‐treated cells, activating the CHK1 and CHK2 signaling pathways. PA further inhibited proliferation and colony‐forming abilities and induced cell cycle arrest at the G0/G1 phase by regulating p53/p21 and CDK2/cyclin E1 expression. Moreover, PA increased the percentage of cells in the subG1 phase and induced apoptosis by activating the Bax/caspase‐9/caspase‐3 intrinsic pathway. In addition, drug resistance (p‐glycoprotein) and cancer stem cell (CD44 and CD133) markers were downregulated after PA treatment. Furthermore, combining PA and cisplatin exhibited synergistic inhibitory activity in A549 and A549/V16 cells. Conclusions: PA induced ROS‐mediated DNA damage, triggered cell cycle arrest and apoptosis, attenuated drug resistance and cancer stem cell phenotypes, and synergistically inhibited proliferation in combination with cisplatin. These findings suggest that PA has the potential to be used for the treatment of NSCLC with or without VCR resistance. [ABSTRACT FROM AUTHOR]

Medicago is a genus of legumes (Fabaceae) that resemble common clovers with pinnately trifoliate leaves and spirally coiled seed pods, and Medicago sativa is a famous forage crop throughout the world. In this study, we systematically assembled the complete plastid genomes of 18 Medicago species, representing 35 Medicago accessions, whose genome size ranged from ~119 to 125 kb, and identified one novel inverted repeat (IR) in two accessions of Medicago soleirolii (PI537242 and PI537243), albeit of no IRs in the most accessions. We built a phylogenetic tree based on common protein‐coding sequences of 55 Medicago accessions in 38 species, which were placed into five clades with a divergence since 9.37 million years ago. Global alignment revealed independent genome evolution events, including eight inversions in nine species and four intron losses (ILs) in 10 species, among which four inversions and two ILs have not been reported previously. Within 109–111 unique genes, ndhA, rpl2, and ycf3 were under positive selection in 54 Medicago accessions. Finally, by aligning chloroplast genes against the nuclear genome assembly of M. sativa cultivar "Zhongmu No.1", we found that a large number of chloroplast gene fragments were horizontally transferred to nuclear chromosomes in alfalfa, especially on the chr3:47518422–48722257 coordinates of chromosome 3. Our comprehensive exploration of Medicago chloroplast genomes provided insights for the understanding of Medicago diversity and their genomic evolution events. [ABSTRACT FROM AUTHOR]

This article, published in the Plant Biotechnology Journal, explores the role of the OsGA2ox9 gene in regulating seed dormancy and gibberellin (GA) metabolism in rice. The study found that OsGA2ox9 is highly expressed in early developing seeds and plays a crucial role in maintaining low levels of bioactive GAs during seed development, thereby inhibiting germination. Loss-of-function mutants of OsGA2ox9 showed advanced germination and preharvest sprouting, while overexpression of the gene resulted in increased seed dormancy. The findings suggest that OsGA2ox9 is involved in the regulation of seed dormancy through GA metabolism and provide insights into the genetic mechanisms underlying preharvest sprouting in rice. [Extracted from the article]

Melanoma is a highly metastatic cancer with a low incidence rate, but a high mortality rate. Patchouli alcohol (PA), a tricyclic sesquiterpene, is considered the main active component in Pogostemon cablin Benth, which improves wound healing and has anti‐tumorigenic activity. However, the pharmacological action of PA on anti‐melanoma remains unclear. Thus, the present study aimed to investigate the role of PA in the proliferation, cell cycle, apoptosis and migration of melanoma cells. These results indicated that PA selectively inhibited the proliferation of B16F10 cells in a dose‐ and time‐dependent manner. It induced cell cycle arrest at the G0/G1 phase and typical morphological changes in apoptosis, such as chromatin condensation, DNA fragmentation and apoptotic bodies. In addition, PA reduced the migratory ability of B16F10 cells by upregulating E‐cadherin and downregulating p‐Smad2/3, vimentin, MMP‐2 and MMP‐9 expression. PA was also found to strongly suppress tumour growth in vivo. Furthermore, PA combined with cisplatin synergistically inhibited colony formation and migration of B16F10 cells and attenuated the development of resistance to treatment. Therefore, the results of this study indicate that PA may play a pivotal role in inducing apoptosis and reducing the migration of melanoma cells, and may thus be a potential candidate for melanoma treatment. [ABSTRACT FROM AUTHOR]

Herein, we present a chiral boro‐phosphate catalyzed atroposelective asymmetric transfer hydrogenation method, leading to a family of axially chiral styrene‐type allylalcohols. This dynamic kinetic resolution approach portrays simple procedure, mild conditions and good enantiocontrol (51–95% ee), thus providing an important alternative to assemble the challenging atropisomeric aryl‐acyclic alkene scaffolds. [ABSTRACT FROM AUTHOR]

In order to improve the performance of the transformerless modular multilevel converters (MMC) under AC and DC grid fault conditions, this paper proposes an improved four‐layer capacitor voltage control strategy combined with arm current control. The proposed control strategy consists of overall submodule capacitor voltage averaging control, leg‐balancing control with flexible weight factor W, arm‐balancing control with zero‐sequence suppression, and inner‐arm individual balancing control. The new concept of weight factor W for leg‐balancing control is also originated, considering negative‐sequence current and DC circulating current jointly from power point of view. The proposed approach effectively realizes the capacitor voltage balance, ac‐side current tracking, and unwanted circulating current elimination. The practical implementation of the proposed control strategy and the experimental results from a downscale three‐phase transformerless MMC prototype are presented to validate the performance of the proposed four‐layer capacitor voltage control strategy under grid faults. [ABSTRACT FROM AUTHOR]

Synchrotron radiation based dynamic micro-computed tomography (micro-CT) is a powerful technique available at synchrotron light sources for investigating evolving microstructures. Wet granulation is the most widely used method of producing pharmaceutical granules, precursors to products like capsules and tablets. Granule microstructures are known to influence product performance, so this is an area for potential application of dynamic CT. Here, lactose monohydrate (LMH) was used as a representative powder to demonstrate dynamic CT capabilities. Wet granulation of LMH has been observed to occur on the order of several seconds, which is too fast for lab-based CT scanners to capture the changing internal structures. The superior X-ray photon flux from synchrotron light sources makes sub-second data acquisition possible and well suited for analysis of the wet-granulation process. Moreover, synchrotron radiation based imaging is non-destructive, does not require altering the sample in any way, and can enhance image contrast with phase-retrieval algorithms. Dynamic CT can bring insights to wet granulation, an area of research previously only studied via 2D and/or ex situ techniques. Through efficient dataprocessing strategies, dynamic CT can provide quantitative analysis of how the internal microstructure of an LMH granule evolves during the earliest moments of wet granulation. Here, the results revealed granule consolidation, the evolving porosity, and the influence of aggregates on granule porosity. [ABSTRACT FROM AUTHOR]

Visualization of low-density tissue scaffolds made from hydrogels is important yet challenging in tissue engineering and regenerative medicine (TERM). For this, synchrotron radiation propagation-based imaging computed tomography (SR-PBI-CT) has great potential, but is limited due to the ring artifacts commonly observed in SR-PBI-CT images. To address this issue, this study focuses on the integration of SR-PBI-CT and helical acquisition mode (i.e. SRPBI-HCT) to visualize hydrogel scaffolds. The influence of key imaging parameters on the image quality of hydrogel scaffolds was investigated, including the helical pitch (p), photon energy (E) and the number of acquisition projections per rotation/revolution (Np), and, on this basis, those parameters were optimized to improve image quality and to reduce noise level and artifacts. The results illustrate that SR-PBI-HCT imaging shows impressive advantages in avoiding ring artifacts with p = 1.5, E = 30 keVand Np = 500 for the visualization of hydrogel scaffolds in vitro. Furthermore, the results also demonstrate that hydrogel scaffolds can be visualized using SR-PBI-HCT with good contrast while at a low radiation dose, i.e. 342 mGy (voxel size of 26 mm, suitable for in vivo imaging). This paper presents a systematic study on hydrogel scaffold imaging using SR-PBI-HCT and the results reveal that SR-PBI-HCT is a powerful tool for visualizing and characterizing low-density scaffolds with a high image quality in vitro. This work represents a significant advance toward the non-invasive in vivo visualization and characterization of hydrogel scaffolds at a suitable radiation dose. [ABSTRACT FROM AUTHOR]

The Shuangqishan Au deposit (>15 t) is located in the Dehua‐Youxi‐Yongtai goldfield of the southeastern Cathaysia Block, South China. There are three stages of granites in the Shuangqishan Au deposit, the pre‐mineralization granite porphyry formed in the Middle Jurassic (~166.0 ± 0.8 Ma), the metallogenic granite porphyry and monzonite porphyry formed in the late stage of the Late Jurassic (153–151 Ma), the post‐mineralization granites (granite porphyry, the masanophyre, the dioritic porphyrite) formed in the Early Cretaceous (129.0–120.0 Ma). All rocks are characterized by high‐K calc‐alkaline and shoshonities series, the per‐mineralization granites are enriched in Rb, Th, K, Zr, and Hf, depleted in Ba, P, and Ti, significant negative Eu anomaly and distinctly tetrad effect with highly fractionated I‐type granitoids characteristics. The metallogenic granites and the post‐mineralization granite porphyry are enriched in K, Rb, Th, Ce, Zr, Hf, and Y, enriched in LREE, strongly depleted in Sr, Ba Ta, P, Ti, have moderate negative Eu anomalies with I‐type granites characteristics. However, the post‐mineralization dioritic porphyrite displays strong depletions Sr, Ta, P, and Ti whereas Rb, Th, Ce, and Sm are enriched, enriched in LREE with weakly negative Eu anomalies. The metallogenic granite porphyry is significantly enriched in Au, As, Sb, W, Mo, and Bi, especially enriched in Au. The Lu‐Hf isotopic data indicate that the magma source comes from the partial melting of the Paleoproterozoic crust, the minor part from the mantle in the Early Cretaceous. Therefore, we propose that the granitoids formed in the subducted plate environment from the Middle Jurassic to the Early Cretaceous, the Late Jurassic I‐type granites (~153–146 Ma), The Shuangqishan Au deposit was formed in the stage from compression to extension, the Early Cretaceous granites (~129–114 Ma) mainly formed in the extensional environment and destroyed gold ore bodies. [ABSTRACT FROM AUTHOR]

Thus, further studies are needed to elucidate the antigen-presenting role of B cells and modulate such function to enhance antitumour T cells for effective tumour treatment. In the models of influenza infection, B cells have been shown to be essential and sufficient for the activation of T cells.[4] However, whether B cells could serve as APCs to drive T-cell responses in TIME remains largely unclear. Chemotherapy tips the scale in favour of cancer-fighting B cells. [Extracted from the article]

Autophagy has emerged as the prime machinery for implementing organelle quality control. In the context of mitophagy, the ubiquitin E3 ligase Parkin tags impaired mitochondria with ubiquitin to activate autophagic degradation. Although ubiquitination is essential for mitophagy, it is unclear how ubiquitinated mitochondria activate autophagosome assembly locally to ensure efficient destruction. Here, we report that Parkin activates lipid remodeling on mitochondria targeted for autophagic destruction. Mitochondrial Parkin induces the production of phosphatidic acid (PA) and its subsequent conversion to diacylglycerol (DAG) by recruiting phospholipase D2 and activating the PA phosphatase, Lipin‐1. The production of DAG requires mitochondrial ubiquitination and ubiquitin‐binding autophagy receptors, NDP52 and optineurin (OPTN). Autophagic receptors, via Golgi‐derived vesicles, deliver an autophagic activator, EndoB1, to ubiquitinated mitochondria. Inhibition of Lipin‐1, NDP52/OPTN, or EndoB1 results in a failure to produce mitochondrial DAG, autophagosomes, and mitochondrial clearance, while exogenous cell‐permeable DAG can induce autophagosome production. Thus, mitochondrial DAG production acts downstream of Parkin to enable the local assembly of autophagosomes for the efficient disposal of ubiquitinated mitochondria. Synopsis: Parkin orchestrates mitophagy by coordinating mitochondrial lipid remodeling and sequential production of mitochondrial phosphatic acid and diacylglycerol. Parkin engages phospholipase D2 (PLD2) to generate mitochondrial phosphatidic acid.Parkin‐mediated mitochondrial ubiquitination recruits the ubiquitin‐binding autophagic receptors, optineurin and NDP52, which promote mitochondrial diacylglycerol production via Lipin‐1.Mitochondrial diacylglycerol production stimulates autophagosome assembly and mitophagy. [ABSTRACT FROM AUTHOR]

Oncogene‐derived metabolic reprogramming is important for anabolic growth of cancer cells, which is now considered to be not simply rely on glycolysis. Pentose phosphate pathway and tricarboxylic acid cycle also play pivotal roles in helping cancer cells to meet their anabolic and energy demands. The present work focused on gankyrin, a relatively specific oncogene in hepatocellular carcinoma (HCC), and its impact on glycolysis and mitochondrial homeostasis. Metabolomics, RNA‐seq analysis, and subsequent conjoint analysis illustrated that gankyrin regulated the pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and mitochondrial function and homeostasis, which play pivotal roles in tumor development. Mechanistically, gankyrin was found to modulate HCC metabolic reprogramming via TIGAR. Gankyrin positively regulated the transcription of TIGAR through Nrf2, which bound to the antioxidant response elements (AREs) in the promoter of TIGAR. Interestingly, TIGAR feedback regulated the transcription of Nrf2 and subsequently gankyrin by promoting nuclear importation of PGC1α. The loop between gankyrin, Nrf2, and TIGAR accelerated glucose metabolism toward the PPP and TCA cycle, which provided vital building blocks, such as NADPH, ATP, and ribose of tumor and further facilitated the progression of HCC. [ABSTRACT FROM AUTHOR]

A nanomaterial with a high payload of nucleic acid drugs and low cytotoxicity is desirable for gene therapy. Herein, a new DNA assembly method triggered by hydrophobic interaction and strengthened by Mg2+ electrostatic interaction for carrier‐free gene transfection is reported. It is discovered that a hydrophobic aggregation‐induced emission dye with a low molecular weight that is modified to an oligonucleotide will greatly change the condensation properties of DNA. The conditions and the possible mechanism of such an aggregation process are carefully investigated. Further, it is revealed that the resultant aggregate is suitable for gene delivery, as in which the oligonucleotides are protected from degradation, and the intracellular permeability is enhanced. For the delivery of Bcl‐2 antisense oligonucleotide, such a system exhibits a high gene transfection efficiency both in vitro and in vivo. Accordingly, an interesting observation is reported in this study that an aggregation‐induced emission dye with a molecular weight much lower than the nucleic acid drugs can cause oligonucleotide aggregation and facilitate gene transfection. Such a delivery system provides a practical and inspiring example for the development of gene therapy in the future. [ABSTRACT FROM AUTHOR]

SUMMARY: Wurfbainia villosa is a well‐known medicinal and edible plant that is widely cultivated in the Lingnan region of China. Its dried fruits (called Fructus Amomi) are broadly used in traditional Chinese medicine for curing gastrointestinal diseases and are rich in volatile terpenoids. Here, we report a high‐quality chromosome‐level genome assembly of W. villosa with a total size of approximately 2.80 Gb, 42 588 protein‐coding genes, and a very high percentage of repetitive sequences (87.23%). Genome analysis showed that W. villosa likely experienced a recent whole‐genome duplication event prior to the W. villosa–Zingiber officinale divergence (approximately 11 million years ago), and a recent burst of long terminal repeat insertions afterward. The W. villosa genome enabled the identification of 17 genes involved in the terpenoid skeleton biosynthesis pathway and 66 terpene synthase (TPS) genes. We found that tandem duplication events have an important contribution to the expansion of WvTPSs, which likely drove the production of volatile terpenoids. In addition, functional characterization of 18 WvTPSs, focusing on the TPS‐a and TPS‐b subfamilies, showed that most of these WvTPSs are multi‐product TPS and are predominantly expressed in seeds. The present study provides insights into the genome evolution and the molecular basis of the volatile terpenoids diversity in W. villosa. The genome sequence also represents valuable resources for the functional gene research and molecular breeding of W. villosa. Significance Statement: The present study reports a high‐quality chromosome‐level reference genome of Wurfbainia villosa with comprehensive genomic, transcriptomic, and metabolic analyses, as well as the identification and functional characterization of 66 terpene synthase (TPS)‐encoding genes, which can provide insights into the molecular genetic basis of the diversity and abundance of volatile terpenoids. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Recently, molecular ferroelectrics have attracted more and more attention due to their structural diversity, low cost of manufacture, and environmental‐friendly processing. However, most of the design strategies for molecular ferroelectrics have focused on the selection and modification of cations, and the use of anions has been rarely reported. Here, introducing distorted [CuBr4]2– tetrahedra, we obtained a high curie temperature (Tc) ferroelectric, [cyclopentylammonium]2CuBr4, with a Tc as high as 393 K, and exceeding commercial and most of reported molecular ferroelectric BaTiO3 (393 K). Variable‐temperature hysteresis loop shows the nonlinear P‐E loop of the crystal under a wide temperature range. Variable‐temperature single‐crystal X‐ray diffraction revealed that the Aizu expression can be written as mmmFmm2. In short, this work will inspire more creative strategies by exploiting the tunability of the anion module. [ABSTRACT FROM AUTHOR]

Chicken internal organs are indispensable parts of the body, but their genetic architectures have not been commonly understood. Herein, we estimated the genetic parameters for heart weight (HW), liver weight (LW), spleen weight (SpW), testis weight (TW), glandular stomach weight (GSW), muscular stomach weight (MSW) and identified single nucleotide polymorphisms (SNPs) and potential candidate genes associated with internal organ weights in an F2 population constructed by crossing broiler cocks derived from Arbor Acres with high abdominal fat content and Baier layer dams (a Chinese native breed). The restricted maximum likelihood (REML) method was applied for genetic parameters estimation of internal organ weights using GCTA software. The results showed that heritabilities of internal organ traits ranged from 0.336 to 0.673 and most of the genetic and phenotypic correlations amongst internal organs weights were positive. A genome‐wide association study (GWAS) was performed based on a mixed linear model (MLM) in GEMMA software. Genotypic data were produced from the whole genome re‐sequenced (26 F0 individuals were re‐sequenced at 10 × coverage; 519 F2 individuals were re‐sequenced at 3 × coverage). A total of 7,890,258 SNPs remained to be analysed after quality control and genotype imputation. The GWAS results indicated that significant SNPs responsible for internal organ traits were scattered on the different chicken chromosomes 1–5, 8, 11, 14, 16, 18, 19 and 27. Amongst the annotated genes, fibronectin type III domain containing 3A (FNDC3A), LOC101748122, membrane palmitoylated protein 6 (MPP6), LOC107049584 and KAT8 regulatory NSL complex subunit 1 (KANSL1) were the most promising candidates for internal organ traits. The findings will provide instrumental information for understanding the genetic basis of internal organ development. [ABSTRACT FROM AUTHOR]

In a high proportion of new energy grids or a 100% new energy source of power grid, the dynamic performance of PMSG under fault conditions is very important. However, the current small signal model lacks detailed and deep analysis of a permanent‐magnet synchronous generator (PMSG)‐based wind power generation under LVRT control. Here, a small signal model of a PMSG under pre‐fault, fault and after fault failure recovery stages are established. This paper employs linear analyses to characterize the dynamic performance of a PMSG‐based wind power generation system under LVRT control and practical generator characteristics. In particular, the conflict between frequency regulation and LVRT is discussed based on the constructed model. On this basis, the impact of dc‐link bandwidth on the system performance during failure recovery stage is discussed, and the active damping method is analysed to improve the performance of PMSG during failure and failure recovery stages. Finally, time‐domain simulations are utilized to verify the analyses and models discussed. The research results in this paper are helpful to promote and improve the performance of PMSG during LVRT conditions. [ABSTRACT FROM AUTHOR]

Background: The contextual and interactive learning research was motivated by the need to enhance the healthcare training effect of caregivers of patients with suspected COVID‐19 infection during quarantine. However, there is a lack of effective approaches to integrating mobile contextual learning into interactive learning. Objectives: Therefore, this study developed a mobile augmented reality‐integration contextual interactive healthcare training system, and then investigated the effects of the proposed system on anxiety, learning effects, perceived support and self‐efficacies. Methods: To validate the effectiveness of the system, we conducted a quasi‐experiment with a sample of 91 caregivers of patients with suspected COVID‐19 infection. Results and conclusions: Results showed that the experimental group with the developed system was superior to the control group with e‐pamphlet instruction in mobile devices, in terms of learning effect, perceived support, self‐efficacies and reduction of anxiety during quarantine. Therefore, the mobile contextual interactive healthcare training system could be useful to improve caregivers' self‐efficacies as well as their ability to care for patients in the context of COVID‐19 infection prevention. Implications: This is one of the few studies of the effective approach for technology‐enhanced healthcare education in the COVID‐19 pandemic. Some corresponding suggestions are proposed: implementing mobile contextual interactive training activities to enhance caregivers' knowledge, skills and self‐efficacies; involving social interactions to relieve caregivers' anxiety; providing professional communications and support while facing difficulties in taking care of patients with suspected COVID‐19 infection. Lay Description: What is already known about this topic: The conventional printed materials or pamphlets on mobile devices are provided most in healthcare, with minimal interactions in the situation of the COVID‐19 Pandemic.Contextual interactive learning could contribute to the enhancement of caregivers' communication and self‐efficacy of learning, thereby reducing the patients' stress and anxiety, which compared with pamphlet‐based healthcare education.Previous studies have indicated that AR games have a beneficial impact on the physical activity and mental health of their players during the COVID‐19 pandemic, which helps them to decrease depression and anxiety. What this paper adds: A mobile AR‐integration contextual interactive healthcare training system is proposed to help caregivers with suspected COVID‐19 infection.The experimental results showed that the proposed system promoted the impact of the contextual interactive healthcare training on caregivers' anxiety, learning effects, perceived support and self‐efficacies. Implications of study findings for practitioners: The contextual interactive learning plays an important role in healthcare training. When the caregivers learn healthcare education content, more focus should be placed on the mobile AR‐integration contextual interactive healthcare training than conventional pamphlet‐based healthcare instructions.Relieving the anxiety of caregivers and avoiding them from infection is attainable with the use of AR‐integration contextual interactive healthcare training system.The proposed system of AR‐integration contextual interactive healthcare training could be extended to other healthcare aspects, such as the training of caregivers who provide care for ICU or infectious patients. [ABSTRACT FROM AUTHOR]

In the past two decades, algorithms for multiple‐point statistics (MPS) have been applied in many fields. However, 3D training datum or data (TD) is difficult to be obtained. Two‐dimensional geological cross‐sections from boreholes or geophysical data with high reliability are usually used to explain geological phenomena and are relatively easier to be acquired. In this study, a step‐wise algorithm that combines sequential process and global optimization is presented. Constructing 3D TD set and corresponding pattern databases that extended from 2D cross‐sections at each scale is one of the key steps after presetting the simulation parameters. The following step is constructing an initial model at the coarsest scale with the pattern databases. The iterative Expectation Maximum‐like (EM‐like) optimization process is implemented to obtain the final realization. Each iteration is conducted with a multiscale strategy. Simulation examples of the regional geological structures show that the stratigraphic sequence can be reasonably kept and reproduced. Also, the randomness and effectiveness of the microstructure model are verified by calculating the proportion of grains, fractal dimension and the curve of two‐point connectivity probability function. Key Points: A novel multiple‐point statistics simulation method for constructing 3D geological structures based on 2D geological cross‐section(s) is presentedBased on initial model constructed by the sequential process at the coarsest scale, final realizations are optimizedThe simulation of regional geological structures and microstructures proved that the algorithm can reconstruct 3D structures effectively [ABSTRACT FROM AUTHOR]

Premise: Pollinator sharing of co‐flowering plants may result in interspecific pollen receipt with a fitness cost. However, the underlying factors that determine the effects of heterospecific pollen (HP) are not fully understood. Moreover, the cost of stigma closure induced by HP may be more severe for plants with special touch‐sensitive stigmas than for plants with non‐touch‐sensitive stigmas. Very few studies have assessed HP effects on stigma behavior. Methods: We conducted hand‐pollination experiments with 10 HP donors to estimate HP effects on stigma behavior and stigmatic pollen germination in Campsis radicans (Bignoniaceae) at low and high pollen loads. We assessed the role of phylogenetic distance between donor and recipient, pollen size, and pollen aperture number in mediating HP effects. Additionally, we observed pollen tube growth to determine the conspecific pollen‐tube‐growth advantage. Results: Stigma behavior differed significantly with HP of different species. Pollen load increased, while pollen size decreased, the percentage of permanent closure and stigmatic germination of HP. Stigmatic HP germination increased with increasing aperture number. However, HP effects did not depend on phylogenetic distance. In addition, conspecific pollen had a pollen‐tube‐growth advantage over HP. Conclusions: Our results provide a good basis for understanding the stigma‐pollen recognition process of plant taxa with touch‐sensitive stigmas. We concluded that certain flowering traits drive the HP effects on the post‐pollination period. To better understand the impact of pollinator sharing and interspecific pollen transfer on plant evolution, we highlight the importance of evaluating more factors that determine HP effects at the community level. [ABSTRACT FROM AUTHOR]

Attempts to determine why some patients respond to electroconvulsive therapy (ECT) are valuable in schizophrenia. Schizophrenia is associated with aberrant dynamic functional architecture, which might impact the efficacy of ECT. We aimed to explore the relationship between pre‐treatment temporal variability and ECT acute efficacy. Forty‐eight patients with schizophrenia and 30 healthy controls underwent functional magnetic resonance imaging to examine whether patterns of temporary variability of functional architecture differ between high responders (HR) and low responders (LR) at baseline. Compared with LR, HR exhibited significantly abnormal temporal variability in right inferior front gyrus (IFGtriang.R), left temporal pole (TPOsup.L) and right middle temporal gyrus (MTG.R). In the pooled patient group, ∆PANSS was correlated with the temporal variability of these regions. Patients with schizophrenia with a distinct dynamic functional architecture appear to reveal differential response to ECT. Our findings provide not only an understanding of the neural functional architecture patterns that are found in schizophrenia but also the possibility of using these measures as moderators for ECT selection. [ABSTRACT FROM AUTHOR]

The ultralow concentration of nucleic acids in complex biological samples requires fluorescence probes with high specificity and sensitivity. Herein, a new kind of spherical nucleic acids (SNAs) is developed by using fluorescent π‐conjugated polymers (FCPs) as a light‐harvesting antenna to enhance the signal transduction of nucleic acid detection. Specifically, amphiphilic DNA‐grafted FCPs are synthesized and self‐assemble into FCP‐SNA structures. Tuning the hydrophobicity of the graft copolymer can adjust the size and light‐harvesting capability of the FCP‐SNAs. We observe that more efficient signal amplification occurs in larger FCP‐SNAs, as more chromophores are involved, and the energy transfer can go beyond the Förster radius. Accordingly, the optimized FCP‐SNA shows an antenna effect of up to 37‐fold signal amplification and the limit of detection down to 1.7 pM in microRNA detection. Consequently, the FCP‐SNA is applied to amplified in situ nucleic acid detecting and imaging at the single‐cell level. [ABSTRACT FROM AUTHOR]

Solid state transformer (SST) is designed as a power transmission device between AC grids and DC grids. However, the power fluctuation causes unbalanced power sharing among dual active bridge (DAB) converters and large voltage fluctuations on dc buses. Here, an adaptive virtual impedance control (AVIC) strategy is proposed to improve the balance performance of SST. Adaptive virtual impedance controller gets the same dynamic response for DAB converters, which matches dynamic impedance of DAB converters. Thereby the power balance can be achieved even the load changes. Meanwhile, an adaptive feedforward control scheme is proposed to reduce the influence of load fluctuation on DC bus voltage. The adaptive feedforward scheme also considers the parameter mismatch, thereby the balance of SST will not be destroyed. Moreover, the balanced power sharing achieved by adaptive controller eliminates the difference between actual transmission power and compensation power in each rectifier, which further suppresses the intermediate capacitor voltage fluctuations. Finally, simulation and StarSim experimental results verified the correctness and effectiveness of the proposed control strategy. [ABSTRACT FROM AUTHOR]

The manipulator workspace is an essential element in the field of manipulator research and is of great significance for manipulator motion planning. However, little research has been conducted on dividing the manipulator workspace into working subspaces. No precise division method has been proposed; the inverse kinematics of multiple solutions in manipulator trajectory planning may also cause abrupt joint changes, thus affecting the planned trajectory. The article proposes a working subspace division method for all ball‐wrist 6DOF(degree‐of‐freedom) manipulators that satisfy the Piper criterion to address the above problems. The kinematic model of the manipulator is established, and the Jacobi matrix of the manipulator is obtained. The space of joints of the manipulator is divided into unique domains containing only single inverse kinematic solutions by means of singular trajectory lines when the determinant of the Jacobi matrix is zero; The solution from the joint space to the workspace is achieved by a nonlinear mapping, which completes the partitioning of the work subspace, and each work subspace contains only unique inverse kinematic solutions. When trajectory planning is carried out from the independent area of a single workspace to the overlapping area of multiple workspaces, selecting the inverse kinematic solution in a single working subspace can effectively avoid abrupt changes in the joints of the manipulator and trajectory misalignment caused by numerous inverse solution selection problems and make the planned trajectory smooth and consistent with the operational requirements of each scene. [ABSTRACT FROM AUTHOR]

To solve the problem of low efficiency of the dual active bridge (DAB) converter under the traditional single‐phase‐shift control, a natural soft‐switching current stress optimisation (NSS‐CSO) method is proposed by considering the current stress optimisation and soft‐switching operation under dual‐phase‐shift (DPS) control. This study establishes the current stress and the soft‐switching analytical models of the DPS control global mode. Based on these models, the Karush–Kuhn–Tucker (KKT) condition is used to analyse the influence of the current stress optimisation methods on the efficiency when all switches achieve controlled soft‐switching or some switches achieve natural soft‐switching. It is found that the NSS‐CSO method is more efficient. Furthermore, the optimal phase‐shift ratio combinations and the corresponding current stress extremums of the NSS‐CSO method under various ranges of transmission power and voltage conversion ratio are deduced completely. The results of this study show that the NSS‐CSO method can effectively improve the operation efficiency of the DAB converter over the entire power range when the voltage conversion ratio does not match. Finally, experimental results confirm the accuracy of the theoretical analysis and the effectiveness of the proposed optimisation method. [ABSTRACT FROM AUTHOR]

Previous studies reveal that hydrogen sulphide (H2S) exerts neuroprotection against neurotoxin‐induced Parkinson's disease (PD), but the underlying mechanism remains elusive. The present study was aimed to investigate whether H2S inhibits neuronal apoptosis of substantia nigra with the involvement of autophagy via promoting leptin signalling in 6‐hydroxydopamine (6‐OHDA)‐induced PD rats. In this study, neuronal apoptosis was analysed by TUNEL staining, the activity of caspase‐3 was measured by Caspase‐3 fluorometric assay kit, the expressions of Bax, Bcl‐2, Beclin‐1, LC3II, P62 and leptin were determined by Western blot analysis, and the numbers of autophagosomes and autolysosomes were assessed by transmission electron microscopy. Results showed that NaHS, a donor of exogenous H2S, mitigates 6‐OHDA‐induced the increases in the numbers of TUNEL‐positive cells, the activity of caspase‐3 and the expression of Bax, and attenuates 6‐OHDA‐induced a decrease in the expression of Bcl‐2 in substantia nigra of rats. In addition, 6‐OHDA enhanced the expressions of Beclin‐1, LC3‐II and P62, increased the number of autophagosomes, and decreased the number of autolysosomes in the substantia nigra, which were also blocked by administration of NaHS. Furthermore, NaHS reversed 6‐OHDA‐induced the down‐regulation of leptin expression in the substantia nigra, and treatment with leptin‐OBR, a blocking antibody of leptin receptor, attenuated the inhibition of NaHS on neuronal apoptosis and the improvement of NaHS on the blocked autophagic flux in substantia nigra of 6‐OHDA‐treated rats. Taken together, these results demonstrated that H2S attenuates neuronal apoptosis of substantia nigra depending on restoring impaired autophagic flux through up‐regulating leptin signalling in PD. [ABSTRACT FROM AUTHOR]

Dietary cholesterol oxidation products (COPs) are heterogeneous compounds formed during the processing and storage of cholesterol‐rich foods, such as seafood, meat, eggs, and dairy products. With the increased intake of COPs‐rich foods, the concern about health implications of dietary COPs is rising. Dietary COPs may exert deleterious effects on human health to induce several inflammatory diseases including atherosclerosis, neurodegenerative diseases, and inflammatory bowel diseases. Thus, knowledge regarding the effects of processing and storage conditions leading to formation of COPs is needed to reduce the levels of COPs in foods. Efficient methodologies to determine COPs in foods are also essential. More importantly, the biological roles of dietary COPs in human health and effects of phytochemicals on dietary COPs‐induced diseases need to be established. This review summarizes the recent information on dietary COPs including their formation in foods during their processing and storage, analytical methods of determination of COPs, metabolic fate, implications for human health, and beneficial interventions by phytochemicals. The formation of COPs is largely dependent on the heating temperature, storage time, and food matrices. Alteration of food processing and storage conditions is one of the potent strategies to restrict hazardous dietary COPs from forming, including maintaining relatively low temperatures, shorter processing or storage time, and the appropriate addition of antioxidants. Once absorbed into the circulation, dietary COPs can contribute to the progression of several inflammatory diseases, where the absorbed dietary COPs may induce inflammation, apoptosis, and autophagy in cells in the target organs or tissues. Improved intake of phytochemicals may be an effective strategy to reduce the hazardous effects of dietary COPs. [ABSTRACT FROM AUTHOR]

Enzyme engineering toward catalytic‐tetrad residues usually results in activity loss. Unexpectedly, we found that a directed evolution campaign yielded a beneficial residue A100 in KmCR (a carbonyl reductase from Kluyveromyces marxianus ZJB14056), which is a residue of catalytic tetrad and conserved according to multiple sequence alignment. Inspired by this finding, we performed saturation mutagenesis on all the four residues of catalytic tetrad of KmCR. A number of variants with improved enzymatic activities were obtained. Among them, the variant KmCR_A100S exhibited increased catalytic efficiency (kcat/KM = 47.3 s−1·mM−1), improved stereoselectivity (from moderate selectivity (deP = 66.7%) to strict (S)‐selectivity (deP > 99.5%)), and extended substrate scope, compared to those of KmCR_WT. In silico analysis showed that a relay system was rebuilt in KmCR via the beneficial residue S100. Furthermore, comparison of 11 protein engineering campaigns indicated that the beneficial position is easily overlooked due to the long distance (>10 Å) from ketone substrates. Since CRs share similar catalytic mechanism, the knowledge gained from this study has universal significance to CR engineering. [ABSTRACT FROM AUTHOR]

GLO:F2H7/01nov21:ctm2586-fig-0001.jpg PHOTO (COLOR): 1 Pharmacogenomics (PGx) testing unit and characteristics of the participants, tested genes, drugs, diseases, and variants. Analytics of the clinical implementation of pharmacogenomics testing in 12 758 individuals Pharmacogenomics (PGx) testing is still not widely accepted in routine medical practice, with one of the major obstacles being the lack of evidence to support its clinical benefit.1,2 In the Chinese population, large-scale comprehensive analytics of clinical PGx testing are still lacking.3,4 Thus, we analysed clinical PGx testing for personalised drug treatment in 12,758 Chinese patients at Xiangya Hospital of Central South University, which is one of the first institutions to conduct clinical PGx testing in China. All tested drugs and genes were sorted by the recommendation percentage, which was equal to that of the samples that received PGx recommendations (including risk warnings) divided by the total samples tested for each gene or drug. [Extracted from the article]

Low‐cost and efficient bifunctional catalysts are urgently needed for overall water splitting used in large‐scale energy storage. In this study, we develop a nickel and iron (di)sulfide (Ni−Fe−S) composite catalyst that is in situ synthesized and fixed within the intergranular nanopores inside high pure polycrystalline graphite. Two precursor solutions (reactants) may permeate the graphite intergranular pores to a depth of more than 3.5 mm. The nanoscale pores serve as an array of nanoreactors for the synthesis of the Ni−Fe−S nanoparticles under conditions much milder than usual. The prepared catalyst efficiently catalyzes both the hydrogen and oxygen evolution reactions (HER and OER) in 1.0 M KOH. It delivers a current density of 400 mA cm−2 at a full cell voltage of around 2.3 V without considerable activity decay over 24 h electrolysis. The active species of the catalyst are different for the HER and OER and discussed accordingly. The synthesis strategy based on the nanopores in a monolithic conductive substrate proves to be a simple, efficient, and promising way to prepare electrocatalysts that are cheap, abundant, and industrially attractive. [ABSTRACT FROM AUTHOR]

Xiyanping (XYP) is a Chinese herbal medicine used in the clinic to treat respiratory infection and pneumonia. Recent evidence identified XYP as a potential inhibitor of severe acute respiratory syndrome coronavirus 2, implying XYP as a possible treatment for the coronavirus disease 2019 (COVID‐19). Here, we conducted a prospective, multicenter, open‐label and randomized controlled trial to evaluate the safety and effectiveness of XYP injection in patients with mild to moderate COVID‐19. We consecutively recruited 130 COVID‐19 patients with mild to moderate symptoms from five study sites, and randomized them in 1:1 ratio to receive XYP injection in combination with standard therapy or receive standard supportive therapy alone. We found that XYP injection significantly reduced the time to cough relief, fever resolution and virus clearance. Less patients receiving XYP injection experienced disease progression to the severe stage during the treatment process. No severe adverse events were reported during the study. Taken together, XYP injection is safe and effective in improving the recovery of patients with mild to moderate COVID‐19. However, further studies are warranted to evaluate the efficacy of XYP in an expanded cohort comprising COVID‐19 patients at different disease stages. [ABSTRACT FROM AUTHOR]

In this research, we conducted both laboratory experiments and discrete element simulations to investigate the influence of maximum principal stress level on true‐triaxial unloading behaviors of sandstone samples. The results show that as the level of σ1 at the unloading point increases, the ultimate bearing capacity of sandstone sample is increasingly strengthened, while the sample collapses more easily during the unloading process, and the failure mode of sample changes from mixed tensile‐shear failure to shear failure. With the increase in the level of σ1, the accumulative micro‐cracks at the unloading point and micro‐crack generation rate during the unloading phase exhibit increasing trends, while the ratio between the number of tensile micro‐cracks and shear micro‐cracks generally shows a downward trend. The formation of macro fracture in sandstone sample is closely related to the material inhomogeneity and true‐triaxial stress state. [ABSTRACT FROM AUTHOR]

Pogostemon cablin has been indicated to treat many kinds of diseases and the progression of cancers, such as colorectal cancer. However, the effects of P. cablin extract (PPa extract) against acute myeloid leukemia have not been investigated. Thus, this study explored the anticancer potential of PPa extract and its mechanism in HL‐60 cells. The MTT assay results showed that PPa extract significantly inhibited the proliferation of HL‐60 cells in a dose‐dependent manner and affected cell morphology, causing cell shrinkage and the formation of debris. PPa extract blocked cell cycle progression at the G0/G1 phase in a dose‐ and time‐dependent manner and induced cell apoptosis, as shown by the observation of DNA fragments and apoptotic bodies. Furthermore, PPa extract caused the accumulation of a population of cells at G0/G1 phase via a reduction in p‐Rb, increasing p21 expression, and downregulating cell cycle regulator protein expression. Then, PPa extract was found to activate the extrinsic and intrinsic apoptosis pathways, leading to cell death. These data demonstrated that PPa extract exerted inhibitory activity and triggered cell apoptosis in HL‐60 cells and that PPa extract might be a chemopreventive agent for cancer therapy. [ABSTRACT FROM AUTHOR]

KLF3 is a member of the Kruppel‐like factor (KLF) family of transcription factors, and plays an important role in several biological processes, including adipogenesis, erythropoiesis and B‐cell development. The purposes of this study are to search for polymorphisms of KLF3 coding region and to provide functional evidence for abdominal fat in chickens. A total of 168 SNPs in KLF3 coding region were detected in a unique chicken population, the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF). Of which three single nucleotide polymorphisms (g.3452T > C, g.8663A > G and g.10751G > A) were significantly correlated with abdominal fat weight (AFW) and abdominal fat percentage (AFP) of 329 birds from the 19th generation of NEAUHLF (FDR < 0.05). The reporter gene assay was performed to verify functionality of these three SNPs in both ICP‐1 and DF1 cells. Results showed that the luciferase activity of G allele was significantly higher than that of A allele in g.10751G > A (p < 0.05). However, there were no significant differences between different alleles of others two SNPs in luciferase activity. Overall, KLF3 is an important candidate gene that affects chicken abdominal fat content, and the g.10751G > A is a functional variant that potential would be applied to marker‐assisted selection (MAS) for selective breeding programme. [ABSTRACT FROM AUTHOR]