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Transition‐metal catalyzed asymmetric allylic substitution with alkyl and heteroaryl carbon nucleophiles has been well‐established. However, the asymmetric allylic arylation of acyclic internal alkenes with aryl nucleophiles remains challenging and underdeveloped. Herein we report a stereospecific 3‐aza‐Cope rearrangement interrupted asymmetric allylic substitution‐isomerization (Int‐AASI) that enables asymmetric allylic arylation. By means of this stepwise strategy, both enantioenriched allylic arylation products and axially chiral alkenes could be readily obtained in high enantioselectivities. Experimental studies support a mechanism involving a cascade of asymmetric allylic amination, stereospecific 3‐aza‐Cope rearrangement and alkene isomerization. Density functional theory studies detailed the reasons of achieving the high chemoselectivity, regioselectivity, stereoselectivity and stereospecificity, respectively. [ABSTRACT FROM AUTHOR]

An unprecedented heavy rainfall event in China ("21.7" extreme rainfall event) was simulated using the global variable‐resolution model (MPAS‐Atmosphere) across the scales (4, 8, 16 and 50 km). Although almost all experiments at different resolutions reproduce the spatiotemporal characteristics of precipitation, the simulated precipitation intensity from high to low is 16, 8, 50, and 4 km, with the 16 km simulation being closest to the observations. Precipitation magnitude is prominently influenced by the difference in simulated large‐scale circulation across a range of grid spacings. Further analysis revealed that the differences in latent heating across scales affect the geopotential height and wind field by altering temperature. The latent heating in 4 km simulation is the minimum while the 16 km simulation is maximum. More latent heating release leads to the low‐level pressure depression, amplifies the water vapor flux convergence, produces stronger upward motion and more clouds, and ultimately results in stronger precipitation. The sensitivity experiments for turning off latent heating tendencies during the event showed that the latent heat release has positive feedback on the "21.7" heavy rainfall event. This study highlights the importance of scale‐awareness of latent heat at different resolutions and suggests that the difference in simulated latent heat release during the event is the main reason for simulated different atmospheric circulation and precipitation across scales. Plain Language Summary: Due to the advancements in the numerical computing power, numerical weather prediction models (NWP) are operating at horizontal grid spacing ranging from 1 to 10 km. This study evaluates the simulation performance of the global variable‐resolution model MPAS‐A for a heavy precipitation event and investigates the influence of scale‐aware convective parameterizations on modeling rainfall at horizontal resolutions across the scales (4, 8, 16 and 50 km). The results show that 4 km simulation exhibits the weakest precipitation while the simulated precipitation at 16 km is the strongest. The difference in precipitation simulated by four experiments across scales derives from the variations in large‐scale circulation simulated with different refined resolutions. Further analysis revealed that the differences in latent heat at different resolutions ultimately lead to the changes in geopotential height and large‐scale wind field by altering temperature. 4 km experiment simulates less latent heat than other lower‐resolution experiments. Owing to the positive feedback of the latent heat release on precipitation, 4 km experiment simulates the minimum precipitation. This work highlights that latent heat plays a vital role in simulation of synoptic condition and precipitation. Key Points: Precipitation is influenced by the difference in simulated atmospheric circulation across a range of grid spacingsThe differences in simulated latent heat release across scales affect the geopotential height and wind field by altering temperatureThe latent heat release has positive feedback impact on the "21.7" heavy precipitation event [ABSTRACT FROM AUTHOR]

Antifungal‐resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine‐resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DbCM) is characterized by diastolic dysfunction, which progresses into heart failure and aberrant electrophysiology in diabetic patients. Dyslipidemia in type 2 diabetic patients leads to the accumulation of lipid droplets (LDs) in cardiomyocytes and results in lipid toxicity which has been suggested to drive DbCM. It is aimed to explore potential pathways that may boost LDs degradation in DbCM and restore cardiac function. LDs accumulation resulted in an increase in lipid toxicity in DbCM hearts is confirmed. Microlipophagy pathway, rather than traditional macrolipophagy, is activated in DbCM hearts. RNA‐Seq data and Rab7‐CKO mice implicate that Rab7 is a major modulator of the microlipophagy pathway. Mechanistically, Rab7 is phosphorylated at Tyrosine 183, which allows the recruitment of Rab‐interacting lysosome protein (Rilp) to proceed LDs degradation by lysosome. Treating DbCM mice with Rab7 activator ML‐098 enhanced Rilp level and rescued the observed cardiac dysfunction. Overall, Rab7‐Rilp‐mediated microlipophagy may be a promising target in the treatment of lipid toxicity in DbCM is suggested. [ABSTRACT FROM AUTHOR]

Metal–N–C single‐atom catalysts, mostly prepared from pyrolysis of metal‐organic precursors, are widely used in heterogeneous electrocatalysis. Since metal sites with diverse local structures coexist in this type of material and it is challenging to characterize the local structure, a reliable structure–property relationship is difficult to establish. Conjugated macrocyclic complexes adsorbed on carbon support are well‐defined models to mimic the single‐atom catalysts. Metal–N4 site with four electroneutral pyridine‐type ligands embedded in a graphene layer is the most commonly proposed structure of the active site of single‐atom catalysts, but its molecular counterpart has not been reported. In this work, we synthesized the conjugated macrocyclic complexes with a metal center (Co, Fe, or Ni) coordinated with four electroneutral pyridinic ligands as model catalysts for CO2 electroreduction. For comparison, the complexes with anionic quadri‐pyridine macrocyclic ligand were also prepared. The Co complex with the electroneutral ligand expressed a turnover frequency of CO formation more than an order of magnitude higher than that of the Co complex with the anionic ligand. Constrained ab initio molecular dynamics simulations based on the well‐defined structures of the model catalysts indicate that the Co complex with the electroneutral ligand possesses a stronger ability to mediate electron transfer from carbon to CO2. [ABSTRACT FROM AUTHOR]

Grylloidea (crickets) and Gryllotalpoidea (mole crickets and ant crickets) are relatively ancient lineages within Orthoptera but their fossil records are not very rich. They are currently considered sister clades within the Gryllidea but with obvious differences in morphology and ecological adaptations. We report a new gryllidean family, †Pseudogryllotalpidae fam. nov. with three new genera and four new species, viz. †Pseudogryllotalpa scalprata gen. et sp. nov., †Unidigitus longialatus gen. et sp. nov., †Petilus zhengi gen. et sp. nov. and †Chunxiania fascia sp. nov. from the mid‐Cretaceous of northern Myanmar (ca. 99 million years ago). Their external and short ovipositors and their modified fossorial forelegs suggest a soil‐inhabiting preference. This new family exhibits a series of 'intermediate' character states between Grylloidea and Gryllotalpoidea and seems to be a 'transitional' fossil group linking these two superfamilies. This new family was resolved as a sister group of the extant Gryllotalpoidea and provides a new insight into the relationship and evolution of Grylloidea and Gryllotalpoidea. [ABSTRACT FROM AUTHOR]

Background: Noninvasive energy‐based device (NI‐EBD) aesthetic procedures has recently gained widespread usage for treating various skin conditions, enhancing skin texture and performing rejuvenation‐related procedures. However, practically all NI‐EBD procedures result in variable degrees of damage to the skin barrier, inducing pathological and physiological processes such as oxidative stress and inflammation, and only a small percentage of individuals possess the innate ability to restore it. Objective: To introduce the concept of integrated skincare and establish standardized operational procedures for perioperative integrated skincare, and furnish a theoretical basis for clinical diagnosis and treatment performed by professional medical aestheticians. Methods: The author leveraged domestic and international guidelines, clinical practice expertise and evidence‐based research, adapting them to suit the specific circumstances in China. Results: The consensus were provided four parts, including concept and essence of integrated skincare, integrated skincare significance during the perioperative phase of NI‐EBD procedures, active ingredients and functions of effective skincare products, standardized perioperative skincare procedure for NI‐EBD procedures and precautions. For the standardized perioperative skincare procedure, four recommendations were listed according to different stages during NI‐EBD procedures. Conclusion: These recommendations create the 'Expert Consensus on Perioperative Integrated Skincare for Noninvasive Energy‐Based Device Aesthetic Procedures in Clinical Practice in China'. [ABSTRACT FROM AUTHOR]

Molting and metamorphosis are important physiological processes in insects that are tightly controlled by ecdysone receptor (EcR) through the 20‐hydroxyecdysone (20E) signaling pathway. EcR is a steroid nuclear receptor (SR). Several FK506‐binding proteins (FKBPs) have been identified from the mammal SR complex, and are thought to be involved in the subcellular trafficking of SR. However, their roles in insects are poorly understood. To explore whether FKBPs are involved in insect molting or metamorphosis, we injected an FKBP inhibitor (FK506) into a lepidopteran insect, Spodoptera litura, and found that molting was inhibited in 61.11% of the larvae, and that the time for larvae to pupate was significantly extended. A total of 10 FKBP genes were identified from the genome of S. litura and were clustered into 2 distinct groups, according to their subcellular localization, with FKBP13 and FKBP14 belonging to the endoplasmic reticulum (ER) group and with the other members belonging to the cytoplasmic (Cy) group. All the CyFKBPs were significantly upregulated in the prepupal or pupal stages, with the opposite being observed for the ER group members. FK506 completely blocked the transfer of EcR to the nucleus under 20E induction, and significantly downregulated the transcriptional expression of many 20E signaling genes. A similar phenomenon was observed after RNA interference of 2 CyFKBPs (FKBP45 and FKBP12b), but not for FKBP13. Taken together, our data indicate that the cytoplasmic FKBPs, especially FKBP45 and FKBP12b, mediate the nuclear localization of EcR, thereby regulating the 20E signaling and ultimately affecting molting and metamorphosis in insects. [ABSTRACT FROM AUTHOR]

Objectives: No consensus regarding the optimal position and location for the measurement of the inter‐rectus distance (IRD) via ultrasound (US) has been reached. By investigating the intra‐ and interimage reliability of IRD measurements taken in different positions and at different locations within and between testers, this study provides a theoretical basis for the current situation. Methods: The IRD was measured via US in 46 women at 42–60 days after delivery at the superior margin of the umbilicus and 3 cm above, 5 cm above and 3 cm below the umbilicus while the women were in the supine, crunch and standing positions. In the interimage test, every participant was tested 2 times by Physician X and 1 time by Physician Y; in the intraimage test, the images collected by Physician X during the first test were saved in the machines, and two measurements were performed by Physician X and one measurement was performed by Physician Y. Paired t tests and intraclass correlation coefficients (ICCs) were calculated. Results: Only the first IRD measurements by tester X and tester Y at 3 cm below the umbilicus in the crunch position were significantly different (9.56 ± 6.00 versus 11.00 ± 5.55) (P <.05). All the ICCs were greater than.75, and the intratester ICCs were greater than or equal to the corresponding intertester ICCs. The ICCs at 3 cm below the umbilicus were the smallest in the supine and crunch positions and the largest in the standing position due to the increased frequency of IRD values of 0. The ICCs for the crunch position were greatest according to the intraimage test but smallest according to the interimage test. The interimage ICCs between the two testers in the supine position at the superior margin, 3 cm above, 5 cm above, and 3 cm below the umbilicus were.972,.974,.975, and.956, respectively. Conclusions: Ultrasound imaging (USI) is a reliable method for measuring the IRD in women in the early postpartum period. The dynamic measurement of the IRD at or above the umbilicus in the supine position by different testers in real time showed the highest reliability. [ABSTRACT FROM AUTHOR]

Axially chiral N‐substituted quinazolinones are important bioactive molecules, which are presented in many synthetic drugs. However, most strategies toward their atroposelective synthesis are mainly limited to the axially chiral arylquinazolinone frameworks. The development of modular synthetic methods to access diverse quinazolinone‐based atropisomers remains scarce and challenging. Herein, we report the regio‐ and atroposelective synthesis of axially chiral N‐vinylquinazolinones via the strategy of asymmetric allylic substitution‐isomerization. The catalysis system utilized both asymmetric transition‐metal catalysis and organocatalysis to efficiently afford trisubstituted and tetrasubstituted N‐vinylquinazolinone atropisomers, respectively. With the meticulous design of β‐substituted allylic substrates, both Z‐ and E‐tetrasubstituted axially chiral N‐vinylquinazolinones were obtained in good yields and high enantioselectivities. [ABSTRACT FROM AUTHOR]

In this study, a global variable‐resolution modeling framework of atmospheric dust and its radiative feedback is established and evaluated. In this model, atmospheric dust is simulated simultaneously with meteorological fields, and dust‐radiation interactions are included. Five configurations of global mesh with refinement at different resolutions and over different regions are used to explore the impacts of regional refinement on modeling dust lifecycle at regional and global scales. The model reasonably produces the overall magnitudes and spatial variabilities of global dust metrics such as surface mass concentration, deposition, aerosol optical depth, and radiative forcing compared to observations and previous modeling results. Two global variable‐resolution simulations with mesh refinement over major deserts of North Africa (V16 km‐NA) and East Asia (V16 km‐EA) simulate less dust emissions and smaller dry deposition rates inside the refined regions due to the weakened near‐surface wind speed caused by better resolved topographic complexity at higher resolution. The dust mass loadings over North Africa are close to each other between V16 km‐NA and the quasi‐uniform resolution (∼120 km) (U120 km), while over East Asia, V16 km‐EA simulates higher dust mass loading. Over the non‐refined areas with the same resolution, the difference between global variable‐resolution and uniform‐resolution experiments also exists, which is partly related to their difference in dynamic time‐step and the coefficient for horizontal diffusion. Refinement at convection‐permitting resolution around the Tibetan Plateau (TP) simulates less dust due to its more efficient wet scavenging from resolved convective precipitation around the TP against coarse resolution. Plain Language Summary: Mineral dust plays an important role in Earth's climate system. Numerical simulation of dust and its impacts on a regional scale still has large uncertainties, partly due to the relatively coarse horizontal resolution. Limited‐area simulation at relatively high resolution can generally better characterize dust and its impacts on a regional scale; however, lateral boundary conditions may introduce some numerical issues and constrain regional feedback, such as dust‐cloud and dust‐radiation interactions, to large‐scale circulation. In this study, a novel modeling framework of atmospheric dust and its climatic feedbacks with the capability of global variable‐resolution simulation is established and evaluated. The model produces reasonable global spatial distributions of dust compared to observations and previous studies. The difference between the simulations at global quasi‐uniform resolution and global variable resolution with regional refinement over East Asia and North Africa is significant, particularly with refinement at convection‐permitting resolution. This model may be used in the future to provide new insights into the impacts of dust on regional and global climate systems. Key Points: A modeling framework of atmospheric dust with the capability of global variable‐resolution simulation is introduced and evaluatedExperiments with regional refinement produce less dust emissions and mass loading and smaller dry deposition due to weaker surface windRefinement at convection‐permitting resolution simulates stronger wet scavenging and less dust mass compared to coarse resolution [ABSTRACT FROM AUTHOR]

Background: TERT gene amplification (TGA) is a mechanism of telomerase reverse transcriptase (TERT) upregulation frequently utilized by acral melanomas (AMs). Currently, the utility of TERT immunohistochemistry (IHC) to predict TGA status in AMs is poorly documented. Methods: AMs (26 primary and 3 metastatic) and non‐acral cutaneous melanomas (6 primary) were subjected to immunohistochemical analysis using anti‐TERT antibody to demonstrate protein expression and fluorescence in situ hybridization (FISH) to assess genomic copy number alteration. The relationship between TERT immunoreactivity and TGA confirmed by FISH was assessed using logistic regression. Results: TERT expression was seen in 50% (13/26) of primary and 100% (3/3) of metastatic AMs and 50% (3/6) of primary non‐acral cutaneous melanomas. TGA was found in 15% (4/26) and 67% (2/3) of primary and metastatic AMs and 17% (1/6) of non‐acral cutaneous melanomas. The intensity of TERT immunoreactivity correlated with TGA (p = 0.04) and a higher TERT copy number‐to‐control ratio in AMs, with a correlation coefficient of 0.41 (p = 0.03). The sensitivity and specificity of TERT immunoreactivity for predicting TGA in AMs were 100% and 57%, with corresponding positive and negative predictive values of 38% and 100%, respectively. Conclusions: The clinical utility of TERT IHC to predict TGA status in AMs appears to be limited given its low specificity and positive predictive value. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX)‐induced cardiotoxicity (DoIC) is a major side effect for cancer patients. Recently, ferroptosis, triggered by iron overload, is demonstrated to play a role in DoIC. How iron homeostasis is dysregulated in DoIC remains to be elucidated. Here, the authors demonstrate that DOX challenge exhibits reduced contractile function and induction of ferroptosis‐related phenotype in cardiomyocytes, evidenced by iron overload, lipid peroxide accumulation, and mitochondrial dysfunction. Compared to Ferric ammonium citrate (FAC) induced secondary iron overload, DOX‐challenged cardiomyocytes show a dysfunction of iron homeostasis, with decreased cytoplasmic and mitochondrial iron–sulfur (FeS) cluster‐mediated aconitase activity and abnormal expression of iron homeostasis–related proteins. Mechanistically, mass spectrometry analysis identified DOX‐treatment induces p53‐dependent degradation of Parkinsonism associated deglycase (Park7) which results in iron homeostasis dysregulation. Park7 counteracts iron overload by regulating iron regulatory protein family transcription while blocking mitochondrial iron uptake. Knockout of p53 or overexpression of Park7 in cardiomyocytes remarkably restores the activity of FeS cluster and iron homeostasis, inhibits ferroptosis, and rescues cardiac function in DOX treated animals. These results demonstrate that the iron homeostasis plays a key role in DoIC ferroptosis. Targeting of the newly identified p53–Park7 signaling axis may provide a new approach to prevent DoIC. [ABSTRACT FROM AUTHOR]

5‐hydroxymethylfurfural (HMF), one of the most significant biomass‐derived renewable resources, has been widely utilized to create furan‐based value‐added chemicals such as 2,5‐diformylfuran (DFF), 5‐hydroxymethyl‐2‐furancarboxylic acid (HMFCA), 5‐formyl‐2‐furancarboxylic acid (FFCA), and 2,5‐furan dicarboxylic acid (FDCA). Indeed, DFF, HMFCA and FFCA are key intermediate products during the oxidation of HMF to FDCA. Herein, this review aims to demonstrate the recent advances in metal‐catalyzed oxidation of HMF into FDCA via two different reaction routes (HMF‐DFF‐FFCA‐FDCA and HMF‐HMFCA‐FFCA‐FDCA). All the four furan‐based compounds are comprehensively discussed by the selective oxidation of HMF. Additionally, various metal catalysts, reaction conditions, and reaction mechanisms used to obtain the four different products are systematically reviewed. It is anticipated that this review will provide related researchers with new perspectives and speed up the development of this field. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a serious epidemic around the globe, and cardiovascular diseases account for the majority of deaths in patients with DM. Diabetic cardiomyopathy (DCM) is defined as a cardiac dysfunction derived from DM without the presence of coronary artery diseases and hypertension. Patients with either type 1 or type 2 DM are at high risk of developing DCM and even heart failure. Metabolic disorders of obesity and insulin resistance in type 2 diabetic environments result in dyslipidaemia and subsequent lipid‐induced toxicity (lipotoxicity) in organs including the heart. Although various mechanisms have been proposed underlying DCM, it remains incompletely understood how lipotoxicity alters cardiac function and how DM induces clinical heart syndrome. With recent progress, we here summarize the latest discoveries on lipid‐induced cardiac toxicity in diabetic hearts and discuss the underlying therapies and controversies in clinical DCM. [ABSTRACT FROM AUTHOR]

Ecological connectivity, as a research method related to spatial ecology and conservation biology, has attracted increasing attention from researchers at home and abroad in recent years. Habitat connectivity, as a key link in ecological connectivity, is of great significance to promote coastal ecological restoration and protection. However, there has been less systematic research about habitat connectivity due to lack of corresponding theories and practices. Therefore, this paper discusses habitat connectivity from three aspects: (1) the concept of habitat connectivity is introduced and clarified; (2) the application of connectivity in artificial habitat and adjacent waters and its relationship with biodiversity conservation are reviewed and illustrated with examples; and (3) the future development trends of this research direction are summarized and prospected in order to provide a scientific basis and useful reference for the related work of coastal restoration projects in China. Generally, this paper argues that an increase in human behaviour irreversibly destroys the connectivity between marine habitats and threatens the spatial and temporal scales of biodiversity and ecosystem services. Therefore, the theoretical research results and practical experience of ecological connectivity should be fully applied to marine ecosystems, and the restoration of degraded ecosystems should be encouraged and supported in ways that promote natural recovery. [ABSTRACT FROM AUTHOR]

Pigmented dermatofibrosarcoma protuberans, also known as Bednar tumors, usually present as a bluish-black discoloration similar to a bruise, which develops into a slow-growing, painless plaque or tumor.[4] In our case, the patient had the features of both pigmented and atrophic DFSP in the same lesion by immunopathogenesis, so the diagnosis of atrophic pigmented dermatofibrosarcoma protuberans was established. Generally, due to the atypical clinical manifestations of atrophic pigmented DFSP, which is frequently neglected by the patients and easily misdiagnosed as benign lesions as in our case. Dermatofibrosarcoma protuberans (DFSP) is an infiltrative cutaneous sarcoma characterized histologically by spindle cells arranged in a storiform pattern, which has a high local recurrence rate but the low metastatic rate and mortality.[1] Several uncommon subtypes of DFSP have been described,[2] such as atrophic pigmented dermatofibrosarcoma protuberans, which are extremely rare and much more difficult to identify clinically. [Extracted from the article]

Tendon–bone interface is prevalent in the human body. It is divided into four zones: tendon (soft tissue), unmineralized fibrocartilage, mineralized fibrocartilage, and bone (hard tissue). Tendon–bone interface is characterized by a cell phenotype gradient that appears in the different zones. The cell phenotype gradients at the tendon–bone interface are orchestrated by specific intracellular molecular mechanisms, extracellular factors, immune signals, and neurovascular factors. These features have inspired scientists to design systems that mimic natural cell phenotype gradients. These biomimetic systems include the construction of cell sheets, regulation of cellular microenvironments, and the design of gradient functional scaffolds. Exploration of methods to mimic cell phenotype gradients is instructional for future clinical applications in reconstituting the tendon–bone interface. The present review elucidates the gradient composition of the tendon–bone interface. The associated regulatory mechanisms and applications are discussed, with the anticipation of creating a mise en scène for future research in interface tissue engineering. [ABSTRACT FROM AUTHOR]

Axially chiral molecules bearing multiple stereogenic axes are of great importance in the field of organic chemistry. However, the efficient construction of atropisomers featuring two different types of stereogenic axes has rarely been explored. Herein, we report the novel atroposelective synthesis of configurationally stable axially chiral B,N‐heterocycles. By using stepwise asymmetric allylic substitution‐isomerization (AASI) strategy, diaxially chiral B,N‐heterocycles bearing B−C and C−N axes that are related to the moieties of axially chiral enamines and arylborons were also obtained. In this case, all four stereoisomers of diaxially chiral B,N‐heterocycles were stereodivergently afforded in high enantioselectivities. Density functional theory (DFT) studies demonstrated that the NH⋅⋅⋅π interactions played a unique role in the promotion of stereospecific isomerization, thereby leading to the highly efficient central‐to‐axial chirality transfer. [ABSTRACT FROM AUTHOR]

Bladder cancer (BLCA) acts as one of the most common malignant tumors in the urinary system without ideal therapy. We performed the present study to explore the role and mechanism of Circ_0002099 in BLCA progression. RNase R treatment assay and actinomycin D treatment assay were used to confirm the circular structure of Circ_0002099. Nuclear‐cytoplasmic fractionation assay and fluorescence in situ hybridization (FISH) were used to indicate the subcellular localization of Circ_0002099. The CCK‐8 assay, colony formation assay, wound‐healing assay, Transwell assay, and animal experiment were used to reveal the facilitative effect of Circ_0002099 on BLCA both in vitro and in vivo. Furthermore, bioinformatic analysis, western blot analysis, FISH, and dual‐luciferase reporter assay were conducted to demonstrate the role of Circ_0002099 in BLCA progression. The results indicated that Circ_0002099 was significantly upregulated in BLCA and could enhance the progression of BLCA in vivo and in vitro. Furthermore, dual‐luciferase reporter assay and FISH assay revealed that Circ_0002099 could regulate miR‐217‐5p/miR‐103a‐3p/Kirsten RAS (KRAS) axis in BLCA. In addition, rescue experiments confirmed that miR‐217‐5p/miR‐103a‐3p could rescue the facilitative effect of Circ_0002099 on BLCA progression. Moreover, FUS (FUSed in sarcoma) was identified to regulate the Circ_0002099‐miR‐217‐5p/miR‐103a‐3p/KRAS axis in BLCA progression. The present study suggested that FUS‐medicated Circ_0002099 could promote the epithelial–mesenchymal transition process in BLCA progression via miR‐217‐5p/miR‐103a‐3p/KRAS axis‐WNT/β‐catenin axis. It could be a promising prognostic biomarker and therapeutic target for BLCA. [ABSTRACT FROM AUTHOR]

Most research on knowledge sharing has examined the construct as an individual difference variable and neglected that it may vary within an individual over a short period of time. Moreover, although researchers have recognized the critical role of leaders in knowledge management practice, scant attention is given to the day‐to‐day dynamics of the relationship between leader behaviours and employee knowledge sharing. Taking a dynamic perspective on knowledge sharing and based on affective events theory, we argue that daily managerial coaching positively affects employees' daily knowledge sharing via the mediating role of daily gratitude. In addition, employees' perceived overqualification would moderate the relation between daily managerial coaching and daily gratitude such that daily managerial coaching would elicit a stronger daily gratitude for employees with lower perceived overqualification. A 10‐working day quantitative diary survey of 122 R&D employees from a large state‐owned enterprise supported our whole theoretical model. The implications of our findings for both theory and practice were discussed. [ABSTRACT FROM AUTHOR]

Relatively little is known about the role of diversity in counterproductive work behaviour (CWB). Drawing on social categorisation theory, we develop and investigate a model of professional diversity on interpersonal CWB through the mediating role of suspicion and examine the role of perceived status differences as an important moderator of this indirect effect. Data from a sample of 63 United States healthcare teams (study 1) and 190 working professionals (study 2) suggest that professional diversity is positively predictive of suspicion within teams and highlights the explanatory role of meta‐stereotype negativity. Further, we find that suspicion may mediate the relationship between diversity and CWB, and that perceived status differences between professions moderate the impact of suspicion, and the indirect effect of diversity, on CWB. These results highlight the importance for human resource management leaders to understand the potentially dysfunctional impact of team diversity and the levers available to lessen these negative consequences. [ABSTRACT FROM AUTHOR]

To improve the castability of Ti‐bearing steel, the knowledge of inclusions formed in liquid steel, affected by the slag composition, must be obtained. In this study, the effect of TiO2 in ladle slag on inclusions in this steel at 1873 K is investigated. Experimental results indicate that Ca–Mg–Al–Ti–O complex inclusions, complex TiN inclusions containing MgO–Al2O3–TiOx cores, Ti–C–S inclusions, and TiC inclusions appear in the steel samples. The cores in TiN inclusions are mainly in the liquid and liquid + spinel fields before slag addition. When the steel reacts with slag containing 0% TiO2 for 1 h, the inclusions in the steel are mostly in the MgO + liquid + spinel and MgO + liquid field and have the highest MgO content. When the steel reacts with slag containing 5%≈20% TiO2 for 1 h, most inclusions are liquid slag + spinel and liquid slag phases. The average liquid fraction in most inclusions is higher than 60%. The ratio of the (mass percentages Ti3+) to (Ti3++mass Ti4+) in most liquid phases is approximately 50%≈70% for these oxide cores. Increasing TiO2 content in slag increases log(aAl2O3/aMgO3), which in turn decreases Mg content in the steel. This decreases MgO content in MgO–Al2O3–TiOx type inclusions. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the efficacy and safety of coronary intervention via distal transradial access (dTRA) in patients with low body mass index (BMI). A total of 67 patients with low BMI who underwent coronary intervention, comprising 29 patients via dTRA and 38 patients via conventional transradial access (cTRA), were retrospectively included. There was no significant difference in the puncture success rate between the two groups (dTRA 96.6%, cTRA 97.4%, P=0.846). Compared with the cTRA group, the success rate of one-needle puncture in the dTRA group was lower (51.7% vs. 81.6%, P=0.020). The compression haemostasis time in the dTRA group was shorter than that in the cTRA group (P  <  0.001). However, the incidence of radial artery occlusion was lower in the dTRA group than in the cTRA group (4.0% vs. 33.3%, P=0.007). In conclusion, coronary intervention via dTRA was safe and effective in patients with low BMI. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to explore the role of galectin‐3 in human epidermal growth factor receptor 2 (HER2)‐positive breast cancer cells and the potential mechanism. Methods: Kaplan–Meier (KM)‐plot and The Cancer Genome Atlas (TCGA) databases were used to study the role of galectin‐3 in the prognosis of HER2‐positive breast cancer. The effects of galectin‐3 on cell proliferation, migration, invasion, and colony formation ability in HER2‐positive breast cancer cells were examined. The relationship between galectin‐3 and important components in the HER2 pathways, including HER2, epidermal growth factor receptor (EGFR), protein kinase B (AKT), and phosphatase and tensin homolog (PTEN), was further studied. Lentivirus and CRISPR/Cas9 were used to construct stable cell lines. Cell counting kit‐8 (CCK‐8) and apoptosis assays were used to study the relationship between galectin‐3 and trastuzumab. The effect of galectin‐3 on cell stemness was studied by mammosphere formation assay. The effects of galectin‐3 on stemness biomarkers and the Notch1 pathway were examined. Tumorigenic models were used to evaluate the effects of galectin‐3 on tumorigenesis and the therapeutic effect of trastuzumab in vivo. Results: HER2‐positive breast cancer patients with a high expression level of LGALS3 (the gene encoding galectin‐3) messenger RNA (mRNA) showed a poor prognosis. Galectin‐3 promoted cancer malignancy through phosphoinositide 3‐kinase (PI3K)/AKT signaling pathway activation and upregulated stemness by activating the Notch1 signaling pathway in HER2‐positive breast cancer cells. These two factors contributed to the enhancement of trastuzumab resistance in cells. Knockout of LGALS3 had a synergistic therapeutic effect with trastuzumab both in vitro and in vivo. Conclusions: Galectin‐3 may represent a prognostic predictor and therapeutic target for HER2‐positive breast cancer. [ABSTRACT FROM AUTHOR]

In this study, we use a tripartite evolutionary game model to analyze the financial support for science-tech enterprises' innovation with government participation. Based on the game model, the study uses replication dynamics to analyze the stability of evolutionary trajectory in the eight scenarios of enterprises, the government, and the financial institutes. Then, we discuss the effect of the reputation multiplier, the efficiency of firms' innovation output, and the positive socio-economic externalities multiplier by simulation as the important innovative points in this study. The study draws the following conclusions: (1) enterprises will choose high R&D intensity instead of low R&D intensity if the output of former exceeds that of the latter, (2) enterprises' R&D output is closely related to the strategy choices of the government and financial institutes, and (3) enterprises can attract government subsidy by boosting economic and social externalities. The government subsidies to enterprises with high R&D intensity will improve the innovation output by the innovation investment and reputation multiplier. So, the government can implement subsidy policy to boost high-intensive R&D activity. Financial institutes' strategy choice between equity investment and debt investment is influenced by investment yield difference and can influence enterprises' R&D intensity choices. [ABSTRACT FROM AUTHOR]

Erythrokeratodermia variabilis et progressiva (EKVP) is a rare genodermatosis of clinical and genetic heterogeneity, characterized by the manifestations of localized or disseminated persistent hyperkeratotic plagues and stationary to migratory transient erythematous patches. The majority of EKVP cases display an autosomal dominant mode of inheritance with incomplete penetrance, although recessive transmission has also been described. Mutations associated with EKVP have been primarily detected in connexin (Cx) genes. We herein reported a Chinese sporadic case of late‐onset EKVP with a novel heterozygous missense mutation c.109G>A (p.V37M) in GJB4 (Cx30.3) gene, which resulted in a significant reduction of GJB4 expression in the epidermis of the patient. In accordance, while wild‐type GJB4 localized at the cell membrane of HeLa cells forming intercellular junctions and intracellular puncta, V37M mutant variant was diffusely expressed within HeLa cells at a considerably lower level. Our findings reveal an essential role of GJB4 in the pathogenesis of EKVP and provides insights into the therapeutic potential of the disease. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM), hypertension and atrial fibrillation (AF) are risk factors for heart failure with preserved ejection fraction (HFpEF). Aim: To examine the effects of the simultaneous control of all three conditions on new‐onset HFpEF in this population. Methods: This prospective cohort study enrolled 552 patients with T2DM, hypertension and AF, but without clinical signs or symptoms of heart failure. The participants were followed up for 5 years to examine the effects of glycaemic control (haemoglobin A1c: <7.0%, 7.0%–8.0% and >8.0%), blood pressure (BP) control (systolic BP: <120, 120–140 and >140 mmHg) or rhythm versus rate control for AF on new‐onset HFpEF. Results: With a follow up of 5 years, the new‐onset HFpEF occurred in 62 of 552 enrolled participants. Among the different control level for diabetes, hypertension and AF, the intensive blood glucose (BG) control, poor BP control and rate control of AF had the highest risk of new‐onset HFpEF, and the conservative BG control, intensive BP control and rhythm control of AF had the lowest risk of new‐onset HFpEF. Multivariable Cox regression analysis showed that both poor BP control (hazard ratio (HR): 1.421, 95% confidence interval (CI): 1.013–1.992, P = 0.042) and rate control of AF (HR: 1.362, 95% CI: 1.006–1.821, P = 0.033) were independently associated with the development of new‐onset HFpEF. Conclusion: This study demonstrated that, besides intensive BP control, conservative BG control and rhythm control of AF were crucial factors to delay the progression of HFpEF among patients with T2DM, hypertension and AF. [ABSTRACT FROM AUTHOR]

The degree of matching between supply and demand for financial support policies is a key factor for policy effectiveness. In this paper, we use policy text computing method that integrates topic mining, text classification, and training set predictions to study the supply and demand matching of China's financial support policies for private enterprises. We find that supply and demand match for policies on diversified financing channels. However, there is mismatch in financial service facilitation policies and local subsidy policies. Our research implies that China's development of a multiple-layer financial market has promoted the diversification of financing channels, which has improved the financing conditions for private enterprises. However, financial service network is still not convenient to facilitate private enterprises. [ABSTRACT FROM AUTHOR]

Aims: Heart failure with preserved ejection fraction (HFpEF) develops in response to hypertensive left ventricular (LV) hypertrophy and is associated with increased cardiovascular events. Although the progression to systolic heart failure is a known consequence of LV hypertrophy and HFpEF, few data are available on the LV geometry change and frequency of deterioration to systolic dysfunction in this population. Methods and results: We evaluated the baseline and follow‐up characteristics in 680 patients with LV hypertrophy and HFpEF in this prospective cohort study. The primary endpoint was 5 year all‐cause mortality. The changes of LV geometry and heart failure transition were analysed. Systolic dysfunction [left ventricular ejection fraction (LVEF) < 50%] occurred in 182 patients (26.8%) during a 5 year follow‐up. Patients with LVEF deterioration were associated with a lower survival rate. Beta‐blocker prescription was a protective factor for preserved LVEF. And concentric LV geometry shifted to eccentric hypertrophy was uncommon (10.6%) during a 5 year follow‐up. Conclusions: A quarter of patients with hypertensive LV hypertrophy and HFpEF progresses to systolic dysfunction during a 5 year follow‐up, which was accompanied by poor clinical outcomes. And beta‐blocker therapy might play a protective role for preserved LVEF in this population. [ABSTRACT FROM AUTHOR]

A high‐performance liquid chromatographic method with a modified QuEChERS extraction for the determination of polycyclic aromatic hydrocarbons (PAHs) in blood serum was developed to investigate the internal exposure level and the carcinogentic toxicity contribution rate of PAHs for pregnant women in Nantong, China. Venous blood (n = 48) was collected in the local hospital and the internal exposure level of 16 PAHs and the contribution rate of carcinogenicity to pregnant women were analyzed. Among all of the detected PAHs, the detection rate of pyrene (77.08%) was the highest, followed by naphthalene (64.58%) and benzo[a]anthracene (BaA, 45.83%). The carcinogenicity contribution rate of BaA (37.37%) was the highest, followed by fluorene (32.96%) and acenaphthylene (22.01%). The results showed that many kinds of carcinogenic PAHs can be detected in the serum of pregnant women in Nantong city, among which BaA should be paid most attention because of its high internal exposure level and carcinogenic risk. Meanwhile, the origins of general PAHs in serum samples were analyzed using the characteristic ratio analysis method. The PAH pollution level of air samples (n = 42) during the collection time of blood samples was also analyzed to compare the possible correlations between the two different results. [ABSTRACT FROM AUTHOR]

Two sets of 48‐h hindcast experiments for Mei‐yu season using non‐hydrostatic global variable‐resolution model (MPAS‐Atmosphere) with regional refinement at 4 km resolution (V4km) and uniform 60 km resolution (U60km) are first‐time conducted to attempt at simulating the Mei‐yu rainfall in 2015 over East China. The analysis focuses on the seasonal average of diurnal variation of precipitation amount (PA), intensity (PI), and frequency (PF). Both simulations reasonably reproduce the spatial distribution of PA. V4km is more skillful in simulating the spatial distributions and magnitudes of PF and PI. The diurnal cycle of Mei‐yu rainfall shows a major early morning peak and a minor afternoon peak, contributed by precipitation during two sub‐periods with distinct synoptic circulations. With strong Mei‐yu in the first sub‐period, the diurnal variation of PA is controlled by nocturnal southwesterly jet. V4km overestimates the morning peak mainly due to its bias in simulating boundary layer inertial oscillation. Although differences in PA between the simulations are small, U60km overestimates PF and underestimates PI. With weak Mei‐yu in the second sub‐period, the diurnal variation of PA is controlled by both synoptic circulation and local convection. At both resolutions, deviations in the large‐scale circulation modulated by a few typhoons lead to positive biases in the morning peak of PA. After removing the typhoon impacts, V4km captures the observed diurnal cycle of PA well, while U60km significantly underestimates PA and PI particularly in the afternoon. Future studies focusing on advancing modeling of southwesterly jet and typhoons may further improve convection permitting simulation of Mei‐yu rainfall. Key Points: Global modeling at V4km is more skillful in reproducing Mei‐yu rainfall characteristics compared to modeling at U60kmWith strong Mei‐yu, differences in rainfall diurnal variation controlled by nocturnal southwesterly jet are small between U60km and V4kmWith weak Mei‐yu, V4km produces better rainfall diurnal variation controlled by multi‐scale processes compared to U60km [ABSTRACT FROM AUTHOR]

The inherently linear polypropylene suffers unsatisfying foaming behavior due to its low melt strength. To overcome this drawback, polypropylene‐/polypropylene‐grafted glycidyl methacrylate/thermoplastic polyester elastomer (PP/PP‐g‐GMA/TPEE) blending foam is prepared by the chemical foaming method in this study. The foaming mechanism of blending was studied from the aspects of the rheological behavior and the crystallization property. The results show that TPEE disperses in the PP matrix with fine particles and forms ideal interfaces, which provide a large number of nucleation sites for the foaming process of blending, inducing heterogeneous nucleation. Both of the 15 wt% and 20 wt% TPEE‐modified PP composites show higher shear viscosity and obvious strain hardening behavior. It has been proved that the cross‐linking network structure formed by TPEE and PP‐g‐GMA reaction improves the melt strength. The cell size decreases from 37.6 to 24.8 μm, and the cell density increases from 2.9 × 106 cells/cm3 to 2.5 × 107 cells/cm3. Compared with PP composites, the foaming window of the PP/PP‐g‐GMA/TPEE composites was widened. [ABSTRACT FROM AUTHOR]

Background. The pathophysiology of keloids is complex, and the treatment for keloids is still an unmet medical need. Our study is aimed at identifying the hub genes among the differentially expressed genes (DEGs) between normal skin tissue and keloids and key pathways in the development of keloids. Materials and Methods. We downloaded the GSE92566 and GSE90051 microarray data, which contain normal skin tissue and keloid gene expression data. GSE92566 was treated as a discovery dataset for summarizing the significantly DEGs, and GSE90051 served as a validation dataset. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, Reactome enrichment analysis, gene set enrichment analysis, and gene set variation analysis were performed for the key functions and pathways enriched in DEGs. Moreover, we also validated the hub genes identified from the protein-protein interaction network and predicted miRNA-hub gene interactions. Results. 117 downregulated DEGs and 204 upregulated DEGs in GSE92566 were identified. Extracellular and collagen-related pathways were prominent in upregulated DEGs, while the keratinization-related pathway was associated with downregulated DEGs. The hub genes included COL5A1, COL5A2, and SERPINH1, which were also validated in GSE90051. Conclusion. This study identified several hub genes and provided insights for the underlying pathways and miRNA-hub gene interactions for keloid development through bioinformatic analysis of two microarray datasets. Additionally, our results would support the development of future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Metamorphosis is one of the most important physiological processes in insects. It is regulated by a serial of ecdysone cascade genes. Recently, lots of microRNAs (miRNAs) were investigated in insects; however, their function in metamorphosis is largely unknown. In the present study, the dynamics of a small RNA population was investigated by RNA sequencing from the midgut of a lepidopteran pest Spodoptera litura during larval–pupal metamorphosis. A total of 101 miRNAs were identified, and 75 miRNAs were differentially expressed during the metamorphic process. The relationship between these differentially expressed miRNAs and 12 ecdysone cascade genes was analyzed by four classical software programs, and a multiple‐to‐multiple regulatory network was found to exist between these miRNAs and their targets. Among them, miR‐14‐3p and its two targets (EcR and E75) were chosen for further validation. MiR‐14‐3p had higher expression level in the 6th instar larvae as compared with either the prepupae or pupae, which was opposite to that of both EcR and E75, two ecdysone cascade genes. Luciferase reporter assay confirmed that both EcR and E75 were regulated by miR‐14‐3p. Interestingly, the 3′ untranslated regions are nearly identical to each other among different transcript variants of the ecdysone cascade genes, including EcR, USP, E75, E74, E78, E93, Hr3, Hr4, Hr39, Krh1 and Ftzf1. Thus, different transcript variants of one ecdysone cascade gene could be regulated by the same miRNA. The above data suggest that the ecdysone signaling pathway is under the tight control of miRNA. These findings expand our understanding of the mechanism of insect metamorphosis and may also provide a novel possibility for the control of pest insects in the future. [ABSTRACT FROM AUTHOR]

By analyzing nonlinear and nonstationary vibration signals from the spindle device of the mine hoist, it is a challenge to overcome the difficulty of fault feature extraction and accurately identify the fault of rotor-bearing system. In response to this problem, this paper proposes a new approach based on variational mode decomposition (VMD), SVM, and statistical characteristics such as variance contribution rate (VCR), energy entropy (EE), and permutation entropy (PE). Comparisons have gone to evaluate the performance of rolling bearing defect by using EMD (Empirical Mode Decomposition), MEEMD (Modified Ensemble EMD), BP (Back Propagation) network, single or multiple statistical characteristics, and different motor loads. The experiment was carried out on the mechanical failure simulator of the main shaft device of the hoist, which verified the reliability and effectiveness of the method. The results show that the diagnosis method is suitable for feature extraction of bearing fault signals, with the highest diagnosis accuracy. It can provide a good practical reference for the fault diagnosis of mechanical equipment of the hoist spindle device and has certain practical value. [ABSTRACT FROM AUTHOR]

Background. Primary percutaneous coronary intervention (PCI) is the best available reperfusion strategy in patients with acute ST-segment elevation myocardial infarction (STEMI). However, PCI is associated with a serious problem known as no-reflow phenomenon, resulting in poor clinical and functional outcomes. This study aimed to compare the influences of different balloon deflation velocity on coronary flow and cardiovascular events during primary PCI in STEM as well as transient hemodynamic changes in in vitro experiments. Method and Results. 211 STEMI patients were randomly assigned to either a rapid or a slow balloon deflation group during stent deployment. The primary end point was coronary flow at the end of PCI procedure, and secondary end points included myocardial infarct size. Transient hemodynamic changes were evaluated through an in vitro experimental apparatus and a computer model. In clinical practice, the level of corrected TIMI frame count (cTFC) in slow balloon deflation after primary PCI was significantly lower than that of rapid balloon deflation, which was associated with smaller infarct size. Numerical simulations revealed that the rapid deflation led to a sharp acceleration of flow in the balloon-vessel gap and a concomitant abnormal rise in wall shear stress (WSS). Conclusion. This randomized study demonstrated that the slow balloon deflation during stent implantation improved coronary flow and reduced infarct size in reperfused STEMI. The change of flow in the balloon-vessel gap and WSS resulted from different balloon deflation velocity might be partly accounted for this results. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is an extremely aggressive neoplasm, which is usually diagnosed in the advanced stage of the disease. Extensive studies have shown a link between chronic inflammation and various types of cancer, including OSCC. Salicylate is a biotransformation product of aspirin, with similar anti‐inflammatory ability to aspirin but lacks aspirin's inhibitory effect on the isolated cyclooxygenase activity. Our study indicates that salicylate sensitizes OSCC to anti‐cancer drugs, but the mechanisms of its action are unclear. Here, OSCC cells were used to evaluate the cytotoxicity of salicylate alone or in combination with cisplatin (CDDP). RPPA proteomic array and Western blotting were employed to determine the signaling pathways affected by salicylate. Salicylate decreased cell survival rate and induced cell apoptosis in OSCC cells but not human normal oral mucosal epithelial cells (hTERT‐OME). The use of sodium salicylate (SS) dramatically sensitized OSCC cells to CDDP. RPPA array showed that SS reduced many oncogenes such as PI3K/mTOR signaling and cancer stem cell (CSC)‐related genes versus control. Western and transcriptional analyses substantiated that salicylate down‐regulated these CSC‐associated genes and the mTOR pathway dose dependently. Salicylate preferentially repressed the ability of sorted ALDH1+ cells to form tumor spheres. Finally, salicylate suppressed tumor growth in vivo, and the combination of salicylate and CDDP further synergistically reduced the growth of tumors. Salicylate hinders OSCC cell growth and sensitizes OSCC cells to CDDP through targeting CSCs and the mTOR signaling pathway. We propose that salicylate is beneficial for OSCC patients, and salicylate may be combined with chemotherapies to effectively treat OSCC patients. [ABSTRACT FROM AUTHOR]

Long‐term use of corticosteroids or local use of tazarotene (TAZ) alone for the treatment of psoriasis cause safety issues and low compliance rates. Combining these two may optimize their efficacy and minimize safety concerns. This study aimed to evaluate the clinical efficacy and safety of a fixed combination of TAZ 0.05% and betamethasone dipropionate 0.05% (BM) for psoriasis vulgaris. A multicenter, randomized, single‐blinded, controlled phase 3 clinical trial was conducted. A total of 600 Chinese subjects with psoriasis vulgaris were randomized (3:1:1) to TAZ/BM cream, TAZ gel or BM cream groups for 6 weeks with an 8‐week follow up. The primary efficacy assessment end‐point was 75% improvement in Psoriasis Area and Severity Index (PASI‐75) at 6 weeks. Secondary outcome assessments included PASI‐90, percentage of PASI decrease and so forth. Safety and treatment‐related adverse events were monitored throughout the study. Our results demonstrated that the TAZ/BM group exhibited statistically significant superiority in PASI‐75 over TAZ (6.74% vs 1.67%) within 2 weeks. After 6 weeks of treatment, PASI‐75 was 44.94% in the TAZ/BM group while 19.17% and 35.00% in the TAZ and BM group, respectively. At the 8‐week follow up, the relapse rate of the TAZ/BM group was significantly lower than the BM group (10.62% vs 29.63%, P = 0.0269) though comparable with the TAZ group (10.00%). The most frequently reported treatment‐related adverse event was mild to moderate level of skin irritation events. TAZ/BM combination has significant advantages over TAZ, including satisfying efficacy, rapid onset and reduced local stimulation. Meanwhile, compared with BM, it has the advantages of longer relief time and reduced clinical relapse rate. The TAZ/BM combination drug provides psoriatic patients an alternative drug with high efficacy and low relapse rate and safety concerns. [ABSTRACT FROM AUTHOR]

Background: Gallbladder cancer (GBC) is the most common cancer type of the biliary tract, and an association has been found between chronic calculous cholecystitis (CCC) and an increased incidence of GBC mortality. An understanding of the relationship between CCC and its carcinogenesis may enable us to prevent and cure GBC. In this study, we attempted to explore changes in the microbiome profile that take place during the transition from chronic cholecystitis mucosa to malignant lesions. Results: Seven paired human GBC and CCC samples were provided by patients who had undergone laparoscopic cholecystectomy or radical cholecystectomy. Mucosal DNA extraction and metagenomic sequencing were performed to evaluate changes in the microbiota between the two groups. We found that GBC patients and CCC patients shared similar stable and permanent dominant species and showed apparent differences in their biliary microbial composition and gene function. Peptostreptococcus stomatis and Enterococcus faecium may potentially play a role in GBC progression. In addition, the metagenomic species profiles, co‐abundance and co‐exclusion correlations, and CAZyme prevalence showed significant differences between the CCC and GBC groups. Conclusion: Our data suggested that changes in the microbiota between CCC and GBC may help deepen our understanding of the complex spectrum of different microbiotas involved in the development of GBC. Although the cohort size was small, this study has presented the first evidence of the existence of an altered biliary microbiota in GBC, which is clearly different from that in CCC patients. [ABSTRACT FROM AUTHOR]

From 2010, porcine epidemic diarrhea virus (PEDV) variants caused sequential outbreaks of disease in Asia and the United States. In this retrospective study, 49 complete spike (S) gene sequences were obtained from PEDV strains collected in China from 2014 to 2016. We observed that variant PEDV strains with novel insertions, deletions, and multiple S gene recombination types were present in China. In addition, mixed infections involving different variant strains were observed in some areas. Based on phylogenetic and recombination analyses, we determined that the newly emerged PEDV variants potentially originated via recombination between the earliest Chinese G1 genogroup strain, JS‐2004‐2 and earlier Korean pandemic strains. These findings provide important information for understanding ongoing PEDV outbreaks and suggest that novel variants make it more difficult to prevent PEDV infection. [ABSTRACT FROM AUTHOR]

Background. This study aimed at presenting a novel method of developing a porcine model of portal vein thrombosis (PVT) in cirrhosis by intravenous administration of thrombin and insertion of a fibered coil. We further investigated changes of biochemical parameters, coagulation, and proinflammatory cytokine expression in the cirrhosis-PVT group. Methods. Twelve male pigs were randomized into the control group (n = 3) and cirrhosis group (n = 9). In cirrhotic pigs, three were randomly selected to establish PVT by ultrasound-guided percutaneous puncture of the main portal vein (MPV) followed by intravenous thrombin administration and fibered coil insertion. Thrombosis in the MPV was detected by abdominal enhanced computer tomography (CT). The changes of hepatic function, coagulation system, and inflammation cytokines were compared among normal, cirrhosis, and cirrhosis with PVT groups. Results. As manifested by the presence of a filling defect in MPV on portal venous-phase CT angiography, fibrin thrombi were formed in the MPV in cirrhotic pigs within one week and persisted for four weeks. Five weeks after surgery, abnormal liver functions occurred in association with PVT formation in cirrhosis. Both coagulation and thromboelastography parameters showed that cirrhosis-PVT pigs exhibited a procoagulant state through hyperfunction of platelets and clotting factors. Interleukin 6 (IL-6) as a potential inflammatory marker stimulated PVT-mediated inflammation activation in cirrhosis. Conclusions. Our study provides in vivo evidence that intravenous injection of a coil and thrombin into MPV under interventional guided devices enables a feasible method in thrombus creation. Further exploration and validation of large-sample cases are required to characterize utilities of this model. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) accounts for 80% of all thyroid cancers and seriously impacts the quality of people's lives. Long noncoding RNAs (lncRNAs) play an important role in PTC. In previous studies, thousands of lncRNAs were screened to study their potential relationships with PTC. The aim of this study was to investigate the effect of RPL34‐AS1 in PTC and to explore its potential mechanisms. Bioinformatic analyses were performed to characterize the possible function and biological features of RPL34‐AS1. Apoptosis, proliferation, and invasion were detected to assess the effect of RPL34‐AS1. Cell proliferation was measured using a Cell Counting Kit‐8 assay. Western blot analysis was used to assess the apoptosis proteins Bax and Bcl‐2. Cell invasion was measured using a Transwell assay. Quantitative real‐time polymerase chain reaction (qRT‐PCR) analysis was performed to examine RPL34‐AS1, miR‐3663‐3P, and RGS4 expression. Dual‐luciferase assay was performed to assess the binding of miR‐3663‐3P by RPL34‐AS1. RIP experiment was used to verify the combination between miR‐3663‐3p and RGS4. We found that overexpression of RPL34‐AS1 could inhibit proliferation and invasion while promoting apoptosis in PTC cell lines. Moreover, RPL34‐AS1 could also competitively bind miR‐3663‐3p and exert its function by regulating the miR‐3663‐3p/RGS4 in PTC cell lines. We found a previously uncharacterized lncRNA, RPL34‐AS1, and studied its function and mechanism in PTC. Our research will provide new insights into PTC and new clues for its clinical treatment. [ABSTRACT FROM AUTHOR]

Aims: Patients with heart failure (HF) are typically designated as having reduced, mid‐range, or preserved ejection fraction (EF) (HFrEF, HFmrEF, or HFpEF, respectively) because of the importance of left ventricular EF (LVEF) on therapeutic decisions and prognosis. However, such designations are not necessarily static, as there are many transitions among the three HF phenotypes during follow‐up. This prospective longitudinal cohort study sought to examine the HF transitions over time and their clinical characteristics, prognosis, and response to medical therapy. Methods and results: We identified 1920 patients from a prospective cohort with a primary diagnosis of HF between 1 January 2007 and 31 December 2012. The enrolled HF patients were re‐classified into three groups on the basis of baseline and 1 year follow‐up echocardiography: HF with improved EF (HFiEF), HF with deteriorated EF (HFdEF), and HF with unchanged EF (HFuEF). The primary outcome was 5 year all‐cause mortality. According to 1 year follow‐up echocardiography, 490 (25.5%) were diagnosed as HFiEF, 179 (9.3%) as HFdEF, and 1251 (65.2%) as HFuEF. Ischaemic heart disease was an independent predictor of HFdEF, and beta‐blocker prescription was an independent predictor of HFiEF. During the 5 year follow‐up, patients with HFdEF had higher mortality, whereas patients with HFiEF had lower mortality. After adjustment, HFiEF, compared with HFuEF, was associated with a 62.1% decreased risk for mortality. Finally, the use of beta‐blockers was associated with improved prognosis of patients with HFiEF and HFuEF. Conclusions: In this cohort of patients with HF, LVEF is a dynamic factor related to coexisting conditions and drug therapy. HFiEF and HFdEF are distinct HF phenotypes with different clinical outcomes than other phenotypes. [ABSTRACT FROM AUTHOR]