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To measure creatine distribution in idiopathic inflammatory myopathy (IIM) patients' myocardial segments and investigate whether cardiovascular magnetic resonance (CMR) chemical exchange saturation transfer (CEST) creatine mapping can detect subclinical myocardial changes, CEST's ability was further compared with other conventional CMR mapping sequences.Forty IIM patients (53.5 ± 10.5 years, 26 males) and eight healthy controls (35.4 ± 6 years, 5 males) underwent CMR scans on a 3.0-T MR scanner. Patients with IIM were further classified into two subgroups according to cardiac troponin T (cTn-T) values: the elevated cTn-T subgroup (n = 14) and the normal cTn-T subgroup (n = 26). Cine imaging, T2 SPAIR, LGE imaging, T1 mapping, T2 mapping, and Cr (creatine) CEST were performed.Cr mapping showed significantly reduced creatine in IIM patients among global myocardium (IIM: 0.109 ± 0.063, controls: 0.121 ± 0.021, p0.05), and decreased creatine signals were detected in all 16 cardiac segments (p0.05). Patients also had significantly prolonged native T1 and decreased enhanced T1 values in each cardiac segment (p0.05). There was no significant difference of LVEF and T2 values between IIM patients and controls. Between the two subgroups, elevated cTn-T was linked with creatine and extracellular volume fraction (ECV) values, providing a global average creatine signal of 0.107 vs 0.112 (p0.05) and 24.7 vs 32.4 (p0.05).Creatine CEST mapping can detect early-stage heart involvement with negative LGE findings in IIM. Compared with T1 mapping, CEST provides increased sensitivity to ECV measurement, making it significantly better than T1, and a promising CMR sequence for screening subclinical myocardial damage.• IIM patients with potential or ongoing heart involvement, elevated ECV, and reduced Cr CEST values could provide valuable information. • ECV and Cr CEST values were closely related to elevated cTn-T.

(±)-Hypecurvone A (1) and B (2), two new undescribed phenyl polyketides, along with seven known analogues (3–9) were isolated from the whole plant of Hypericum curvisepalum. Chiral separation of 1 and 2 yielded two pairs of enantiomers 1a/1b and 2a/2b, respectively. The structures of these compounds were elucidated by extensive spectroscopic analyses and ECD spectra simulations. All isolates exhibited moderate cytotoxicity against human hepatocellular carcinoma SMMC-7721 cells, and compound 3 also showed weak cytotoxicity toward MGC-803 cells. The cytotoxicity of these compounds was found to be related to enhanced mitochondria-mediated apoptosis and inhibition of the G2/M phase of the cell cycle.

Inorganic-organic hybrid aluminoborates represent a subclass of porous materials, which rely on effective construction method and structure-directing agents. Herein, we prepared a series of hybrid aluminoborates through covalent decoration of unsaturated Cd

This study was designed to evaluate the bioequivalence of the newly developed delayed-release oral suspension (test) 40 mg esomeprazole magnesium compared to its marketed counterpart (40 mg; reference) in healthy adult Chinese subjects. We conducted randomized, open-label, two-period, single-dose, two-way crossover trials over a 7-day washout period, comprising a fasting trial and a fed trial. The subjects were administered the test or reference products in a 1:1 ratio at random throughout each period. Then, in the next session, they received the alternate products. Liquid chromatography-tandem mass spectrometry and WinNonlin software were used to assess the bioequivalence of esomeprazole peak plasma concentration (C

The hierarchical porous metal-organic framework (HP-MOF) has emerged as a hot topic in porous materials in consideration of their advantages in storage capacity and catalysis performance. Herein, we report the construction and property investigation of a series of HP-MOFs. A series of isoreticular microporous MOFs featuring the

Eusocial insects can employ various behavioural and physiological disease defences to avoid, resist and tolerate pathogen infections in their closely related and packed colonies, termed social immunity. Recent studies have shown that several molecules serve insect social immunity, including chemical odours, insect venoms, immune-related proteins, etc. However, whether and how microRNAs (miRNAs), whose precursors are processed by Dicer-1, drive social immunity in insect colonies is still unknown. Here, we used a ‘host–pathogen’ system (host: Reticulitermes chinensis; pathogen: Metarhizium anisopliae) to explore the impact of miRNAs on social immunity in termite colonies. We found that RNAi-mediated silencing of Dicer-1 led to decreased miRNA concentration, significantly inhibited carbohydrate and energy metabolism and affected other life processes, such as the immune response and oxidation–reduction reactions, in whole body of the termite. In behavioural defence, silencing Dicer-1 significantly diminished defensive social behaviours such as locomotion, grooming, cannibalism and burial in termite groups when encountering fungal contamination. In physiological defence, Dicer-1 silencing and miR-71-5 stimulation resulted in significantly decreased antifungal activities of termites. Furthermore, both Dicer-1-silenced and miR-71-5 stimulant-treated termite groups exhibited a high level of mortality during fungal contamination. Our findings demonstrated the important role of miRNAs in shaping social immunity in termite colonies, providing insights necessary to understand the potential mechanisms underlying behavioural and physiological disease defences in insects and hence laying the groundwork for miRNA-based pest control.

To evaluate the interrelationship between macular sensitivity and retinal perfusion density (PD) in eyes with myopic macular degeneration (MMD).One hundred and thirty-eight highly myopic eyes from 82 adult participants were recruited. Macular sensitivity was evaluated using the Microperimeter MP-3. Retinal PD was measured using the PLEX Elite 9000 swept source optical coherence tomography angiography. Macular sensitivity values between different categories of MMD and its relationship with optical coherence tomography angiography measurements were evaluated using multivariable linear mixed models, adjusting for age and axial length.Macular sensitivity reduced with increasing severity of MMD (β ≤ -0.95, P0.001), whereas the best-corrected visual acuity was not associated with MMD severity (P0.04). Persons who were older (β = -0.08, P0.001), with longer axial length (β = -0.32, P = 0.005), presence of macular diffuse choroidal atrophy (β = -2.16, P0.001) or worse MMD (β = -5.70, P0.001), and presence of macular posterior staphyloma (β ≤ -2.98, P0.001) or Fuchs spot (β = -1.58, P = 0.04) were associated with reduced macular sensitivity. Macular sensitivity was significantly associated with deep retinal PD in MMD (β = 0.15, P = 0.004) but not with superficial retinal PD (P = 0.62).There was a strong correlation between reduced macular sensitivity and increasing MMD severity, even in mild MMD independent of the best-corrected visual acuity. Furthermore, macular sensitivity was correlated with deep retinal PD, suggesting a vasculature-function relationship in MMD.

Clinical evidence shows that postmenpausal women are almost twice as likely to develop Alzheimer's disease (AD) as men of the same age, and estrogen is closely related to the occurrence of AD. Estrogen receptor (ER) α is mainly expressed in the mammary gland and other reproductive organs like uterus while ERβ is largely distributed in the hippocampus and cardiovascular system, suggesting that ERβ selective agonist is a valuable drug against neurodegenerative diseases with low tendency in inducing cancers of breast and other reproductive organs. In this study we identified a natural product patchouli alcohol (PTA) as a selective ERβ agonist which improved the cognitive defects in female APP/PS1 mice, and explore the underlying mechanisms. Six-month-old female APP/PS1 mice were administered PTA (20, 40 mg · kg

In this paper, in order to explore the development of a titanium-based superalloy with a working temperature of 700°C to 750°C and good ductility at room temperature, using Ti+Al+Ti2AlNb ternary powder as the raw material, the temperature is 1200°C to 1300°C, 30MPa, 1.5h Directly mixed and sintered under hot pressing conditions, a new type of titanium-based superalloy (TiAl+Ti2AlNb) samples were prepared. The fracture morphology of hot-pressed sintered samples and tensile samples used scanning electron microscope (Scanning electron microscope, referred to as SEM) and Electron backscattered diffraction (EBSD) for observation. Discuss the room temperature tensile fracture behavior of a new type of high temperature titanium alloy Ti-Al-Nb, and lay a technical foundation for the development of a new type of high temperature titanium-based alloy with low brittleness at room temperature.

In this study, we calculate the urban land green use efficiency (ULGUE) in the Yangtze River Economic Belt from 2005 to 2019 by using the epsilon-based measure (EBM) model. Further, the spatial-temporal distribution, regional differences and evolution trends of ULGUE in the Yangtze River Economic Belt are investigated in depth by using the Dagum Gini coefficient, Kernel Density estimation and Markov Chain method. The following results are obtained. 1) From the perspective of spatial-temporal evolution, the ULGUE in the Yangtze River Economic Belt show a fluctuating upward trend from 2005 to 2019, and it is manifested as diffusion from downstream to middle and upper reaches. 2) From the perspective of regional differences, there is a relatively obvious imbalance of ULGUE within the Yangtze River Economic Belt, but the differences narrow over time. 3) Considering the distribution dynamic evolution, the box diagram and distribution curve of ULGUE in the Yangtze River Economic Belt have a tendency to move to high values, but there is a more obvious phenomenon of spatial polarization. 4) For the part of time and space transfer, the ULGUE within the Yangtze River Economic Belt show the characteristic of “club convergence”, and the Spatial Markov Chain results show an obvious “spatial spillover” effect.

In this article, well-posedness for two types of bilevel vector equilibrium problems with variable domination structures are introduced and studied. With the help of cosmically upper continuity or Hausdorff upper semi-continuity for variable domination structures, sufficient and necessary conditions are given for such problems to be Levitin-Polyak (LP) well-posed and LP well-posedness in the generalized sense. As variable domination structure is a valid generalization of fixed one, the main results obtained in this article extend and develop some recent works in the literature.

Advanced silicon photonic technologies enable integrated optical sensing and communication (IOSAC) in real time for the emerging application requirements of simultaneous sensing and communication for next-generation networks. Here, we propose and demonstrate the IOSAC system on the silicon nitride (SiN) photonics platform. The IOSAC devices based on microring resonators are capable of monitoring the variation of analytes, transmitting the information to the terminal along with the modulated optical signal in real-time, and replacing bulk optics in high-precision and high-speed applications. By directly integrating SiN ring resonators with optical communication networks, simultaneous sensing and optical communication are demonstrated by an optical signal transmission experimental system using especially filtering amplified spontaneous emission spectra. The refractive index (RI) sensing ring with a sensitivity of 172 nm/RIU, a figure of merit (FOM) of 1220, and a detection limit (DL) of 8.2*10-6 RIU is demonstrated. Simultaneously, the 1.25 Gbps optical on-off-keying (OOK) signal is transmitted at the concentration of different NaCl solutions, which indicates the bit-error-ratio (BER) decreases with the increase in concentration. The novel IOSAC technology shows the potential to realize high-performance simultaneous biosensing and communication in real time and further accelerate the development of IoT and 6G networks., Comment: 11pages, 5 figutres

(±)-Hypecurvone A (

Industrial Wireless Networks (IWNs) play a critical role in industry 4.0 applications. However, industrial control processes require deterministic data delivery with an extremely high reliability, which is challenging in harsh IWN environments. Existing scheduling schemes rely mainly on accurate global synchronization to ensure deterministic transmission, which incurs additional hardware cost and a large communication overhead. To eliminate the synchronization requirements, we propose an asynchronous scheduling model that supports arbitrary time offset between any node pairs. As finding a solution with a given reliability guarantee in this model is a NP-hard problem, we design a probabilistic algorithm based on the Monte Carlo tree search (MCTS) method to generate and verify feasible schedules. The simulation results show that E-MCTS is significantly better in transmission reliability if compared to the classic Monte Carlo tree search algorithm.

Production of reactive oxygen species (ROS) via the activity of respiratory burst oxidase homologs (RBOHs) plays a vital role in multiple layers of the plant immune system, including pathogen-associated molecular pattern-triggered immunity (PTI), damage-associated molecular pattern-triggered immunity (DTI), effector-triggered immunity (ETI), and systemic acquired resistance (SAR). It is generally established that RBOHD is activated by different receptor-like cytoplasmic kinases (RLCKs) in response to various immune elicitors. In this study, we showed that RPM1-INDUCED PROTEIN KINASE (RIPK), an RLCK VII subfamily member, contributes to ROS production in multiple layers of plant immune system. The ripk mutants showed reduced ROS production in response to treatment with all examined immune elicitors that trigger PTI, DTI, ETI, and SAR. We found that RIPK can directly phosphorylate the N-terminal region of RBOHD in vitro, and the levels of phosphorylated S343/S347 residues of RBOHD are sigfniciantly lower in ripk mutants compared with the wild type upon treatment with all tested immune elicitors. We further demonstrated that phosphorylation of RIPK is required for its function in regulating RBOHD-mediated ROS production. Similar to rbohd, ripk mutants showed reduced stomatal closure and impaired SAR, and were susceptible to the necrotrophic bacterium Pectobacterium carotovorum. Collectively, our results indicate that RIPK regulates broad-spectrum RBOHD-mediated ROS signaling during PTI, DTI, ETI, and SAR, leading to subsequent RBOHD-dependent immune responses.

OBJECTIVE: To investigate the level of 25 hydroxyvitamin D [25(OH)D] in late preterm infants and the effect of vitamin D(3) supplementation on the neurobehavioral development of infants and young children. METHODS: In this prospective study, 161 late preterm infants who were admitted from June 2017 to June 2020 were enrolled. According to the level of 25(OH)D in umbilical cord blood, they were divided into three groups: sufficiency group (n=52), insufficiency group (n=53), and deficiency group (n=56). Each group was further divided into subgroup A (vitamin D(3) 800 IU/d) and subgroup B (individualized vitamin D(3) supplementation) using a random number table. The levels of 25(OH)D were measured at 3 months after birth and at the corrected ages of 10 months and 18 months. The neurobehavioral development levels were determined by the Gesell Developmental Scale at the corrected ages of 10 months and 18 months. RESULTS: Within 24 hours and 3 months after birth, the insufficiency group and the deficiency group had a significantly lower level of 25(OH)D than the sufficiency group (P

Chromatin transitions are mediated in part by acetylation/deacetylation post-translational modifications of histones. Histone deacetylases, e.g. sirtuins (Sir-proteins), repress transcription via promotion of heterochromatin formation. Here, we characterize the Sir2 class III histone deacetylase (BbSir2) in the environmentally and economically important fungal insect pathogen, Beauveria bassiana. BbSir2 is shown to contribute to the deacetylation of lysine residues on H3 and H4 histones. Targeted gene knockout of BbSir2 resulted in impaired asexual development, reduced abilities to utilize various carbon/nitrogen sources, reduced tolerance to oxidative, heat, and UV stress, and attenuated virulence. ΔBbSir2 cells showed disrupted cell cycle development and abnormal hyphal septation patterns. Proteomic protein acetylation analyses of wild type and ΔBbSir2 cells, revealed the differential abundance of 462 proteins, and altered (hyper- or hypo-) acetylation of 436 lysine residues on 350 proteins. Bioinformatic analyses revealed enrichment in pathways involved in carbon/nitrogen metabolism, cell cycle control and cell rescue, defense, and mitochondrial functioning. Critical targets involved in virulence included LysM effector proteins and a benzoquinone oxidoreductase implicated in detoxification of cuticular compounds. These data indicate broad effects of BbSir2 on fungal development and stress response, with identification of discrete targets that can account for the observed (decreased) virulence phenotype. This article is protected by copyright. All rights reserved.

The insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) pertain to a highly conservative RNA-binding family that works as a post-transcriptional fine-tuner for target transcripts. Emerging evidence suggests that IGF2BPs regulate RNA processing and metabolism, including stability, translation, and localization, and are involved in various cellular functions and pathophysiologies. In this review, we summarize the roles and molecular mechanisms of IGF2BPs in cancer development and progression. We mainly discuss the functional relevance of IGF2BPs in embryo development, neurogenesis, metabolism, RNA processing, and tumorigenesis. Understanding IGF2BPs role in tumor progression will provide new insight into cancer pathophysiology.

The detection of intracellular nucleic acids is a fundamental mechanism of host defense against infections. The dysregulated nucleic acid sensing, however, is a major cause for a number of autoimmune diseases. In this study, we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for both intracellular DNA- and RNA-induced immune responses. We found that in both human and mouse cells, the deletion of G3BP1 led to the dampened cGAS activation by DNA and the insufficient binding of RNA by RIG-I. We further found that resveratrol (RSVL), a natural compound found in grape skin, suppressed both intracellular DNA- and RNA-induced type I IFN production through inhibiting G3BP1. Importantly, using experimental mouse models for Aicardi–Goutières syndrome, an autoimmune disorder found in humans, we demonstrated that RSVL effectively alleviated intracellular nucleic acid–stimulated autoimmune responses. Thus, our study demonstrated a broader role of G3BP1 in sensing different kinds of intracellular nucleic acids and presented RSVL as a potential treatment for autoimmune conditions caused by dysregulated nucleic acid sensing.

N6-methyladenosine (m6A) RNA methylation is profoundly involved in epigenetic regulation, especially for carcinogenesis and tumor progression. Mounting evidence suggests that methyltransferase METTL3 regulates malignant behaviors of gastric cancer (GC). However, the clinical significance and biological implication of SPHK2 and its related m6A modification in GC remain unclear. In this study, quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry were utilized to detect the expression profiles and prognostic significance of SPHK2 in GC. Here, we showed that increased SPHK2 was signified a poor prognosis of GC patients. Phosphorylation and ubiquitination assays were used to investigate the possible mechanisms of SPHK2-mediated KLF2 expression. SPHK2 can promote the phosphorylation of KLF2, which triggers the ubiquitination and degradation of KLF2 protein in GC. Methylated RNA immunoprecipitation (MeRIP) was performed to uncover the m6A modification of SPHK2 mRNA. METTL3 promotes translation of SPHK2 mRNA via an m6A-YTHDF1-dependent manner. Functionally, SPHK2 facilitates GC cell proliferation, migration and invasion by inhibiting KLF2 expression. SPHK2/KLF2 regulates the cell proliferation, migration, and invasion induced by METTL3 in GC. Overall, our findings reveal that METTL3-mediated m6A modification of SPHK2 contributes to GC progression, which extends the understanding of the importance m6A methylation in GC and represents a potential target for GC therapy.

Objective: To analyze the clinical features and genetic characteristics of two patients with hereditary hemorrhagic telangiectasia (HHT) and to review the relevant literature.Methods: The clinical data of two HHT patients admitted to the author’s hospital between April 2019 and February 2022 were retrospectively analyzed. Meanwhile, the genetic analysis was performed with their consent.Results: The first patient was a 62-year-old woman who had been complaining of shortness of breath and fever for 20 days. Her previous medical history included brain abscess drainage and video-assisted thoracoscopic surgery for a pulmonary hemangioma. A right heart catheterization revealed no pulmonary arterial hypertension, and an abdominal enhanced magnetic resonance imaging revealed multiple arteriovenous malformations in the liver. Her ACVRL1 heterozygous variants were discovered through whole-exon gene testing. The second case involved a 47-year-old woman who had been experiencing chest tightness for the past 2 years. Several years ago, she underwent brain abscess drainage and embolization of a pulmonary arteriovenous fistula. Ultrasound revealed generalized hepatic vascular dilation, and enhanced computed tomography revealed numerous pulmonary venous fistulas scattered in both lungs as well as multiple arteriovenous malformations in the liver. Her whole-exon gene testing revealed that she, like her son, had heterozygous ENG variants.Conclusion: HHT patients may experience infection, bleeding, dyspnea, and other symptoms. Imaging is important in disease diagnosis and management because early detection and treatment can prevent major complications and disability or even death.

Pregnant women's perspectives should be included in the dialogue surrounding the expanding offers of non-invasive prenatal testing (NIPT), especially now that technological possibilities are rapidly increasing. This study evaluated women's experiences with the offer of genome-wide (GW) first-tier NIPT in a national screening program. A nationwide pre-and post-test questionnaire was completed by 473 pregnant women choosing between targeted NIPT (trisomies 21, 18 and 13 only) and GW-NIPT (also other findings) within the Dutch TRIDENT-2 study. Measures included satisfaction, reasons for or against choosing GW-NIPT, anxiety, and opinion on the future scope of NIPT. Most respondents (90.4%) were glad to have been offered the choice between GW-NIPT and targeted NIPT; 76.5% chose GW-NIPT. Main reasons to choose GW-NIPT were 'wanting as much information as possible regarding the child's health' (38.6%) and 'to be prepared for everything' (23.8%). Main reasons to choose targeted NIPT were 'avoiding uncertain results/outcomes' (33.7%) and 'not wanting to unnecessarily worry' (32.6%). Nearly all respondents received a low-risk NIPT result (98.7%). No differences were found in anxiety between women choosing GW-NIPT and targeted NIPT. Most respondents were favorable toward future prenatal screening for a range of conditions, including life-threatening disorders, mental disabilities, disorders treatable in pregnancy and severe physical disabilities, regardless of their choice for GW-NIPT or targeted NIPT. In conclusion, women who chose first-tier NIPT were satisfied with the choice between GW-NIPT and targeted NIPT, and most women were favorable toward a broader future screening offer. Our results contribute to the debate concerning the expansion of NIPT.

Background: Superoxide dismutase (SOD) and inflammatory markers are reported to have association with cardiovascular disease. However, no previous study has assessed the value of SOD and inflammatory markers as predictive indicator of heart failure in patients with diabetes and acute coronary syndrome (ACS) in the same study. Objective: The objective of this study is to compare the predictive implications of SOD activity, C-reactive protein (CRP) and fibrinogen for reduced left ventricular ejection fraction (LVEF) in patients with diabetes and ACS. Method: The study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital affiliated to Shandong First Medical University from January 2016 to January 2021. Result: Despite taking the lowest quartile as reference (OR 0.368, 95% CI 0.493–0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482–0.880, P = 0.005), the SOD activity was exhibited to be the strongest predictive indicator of reduced LVEF, independent of confounding factors. The SOD activity showed the most powerful predictor value for reduced LVEF with the highest area under the receiver operating characteristic curve of 0.658. Conclusions: SOD activity is a stronger predictor of reduced LVEF than CRP and fibrinogen in patients with diabetes and ACS.

A short-term composting process to prepare substrate is an effective way to cultivate oyster mushrooms (Pleurotus spp.), which can increase the yield of mushrooms and lower the rate of contamination in non-industrialized cultivation. Moreover, it is different from the traditional composting processes for fertilizers and lacks systematic study, such as microbial succession and compost quality. In this study, a series of different tests of composting duration (0, 2, 4 and 5 d) were performed. A composting duration of 4-5 d over 58 °C was suitable for mushroom cultivation based on the biological efficiency (BE) range of 69.76-73.41 % and the contamination rate of 0 %. The content of total carbon (TC) continuously decreased during composting, while the content of total nitrogen (TN) reacted in an opposite matter. The final TN and C/N ratios were 1.89 % and 28/1, respectively, which fell well within the optimal range of nutritional requirements for oyster mushroom cultivation. The composting bacteria were more diverse than the fungal species. Caldibacillus, Thermobispora, Thermopolyspora, Thermobacillus and Ureibacillus were the predominant bacterial genera during the thermophilic stage. Co-occurrence patterns of microbial communities and physicochemical properties were performed using a network analysis, which indicated that bacteria can play more efficient roles than fungi in the degradation of organic matter. The structural equation model showed that composting duration significantly affected bacterial diversity, lignocellulose degradation rates, and BE. The correlations between bioinformatics parameters with composting characters and agronomic traits were determined by the Mantel test and showed that the induction of bacterial diversity over time rapidly activated carbon metabolism during short-term composting. This study provides a new idea of agro-waste composting for mushroom cultivation.

Stille cross-coupling reactions catalysed by an ideal catalyst combining the high activity of homogeneous catalysts and the reusability of heterogeneous catalysts are of great interest for C–C bond formation, which is a widely used reaction in fine chemistry. Despite great effort to increase the utilization ratio of surface metal atoms, the activity of heterogeneous catalysts under mild conditions remains unsatisfactory. Herein, we design a proof-of-concept strategy to trigger the room-temperature activity of heterogeneous Au catalysts by decreasing the electron density at the interface of a rationally designed Schottky heterojunction of Au metals and boron-doped carbons. The electron-deficient Au nanoparticles formed as a result of the rectifying contact with boron-doped carbons facilitate the autocleavage of C–Br bonds for highly efficient C–C coupling reactions of alkylbromides and allylstannanes with a TOF value of 5199 h−1 at room temperature, surpassing that of the state-of-the-art homogeneous catalyst.

We are interested in the existence of positive and sign-changing solutions for a fractional Kirchhoff equation. Under some mild conditions on the potentials $ V $ and $ h $, using variational methods, we prove the existence of positive ground state solutions and least energy sign-changing solutions.

Heterogeneous catalysts have been developed for C-C coupling reactions, but stand low activity and always proceed under harsh conditions. Photocatalytic Stille cross-coupling reaction as a green catalytic method for C-C bond formation is of great interest for a wide range of scientists but still lacks stable and highly efficient catalysts. Herein, we have designed an Au nanoparticle-graphitic carbon nitride heterojunction as an outstanding photo-catalyst for artificial photosynthesis in Stille cross-coupling reaction. The interface effect between metal and semiconductor makes electron rectify and prevents the recombination of electron-hole pairs. Moreover, the efficiency of Au nanoparticle catalysts could be adjusted by gold contents. Thus the turnover frequency(TOF) value reached the highest level of 788 h−1 over the optimal heterojunction catalyst. Most importantly, the C-C bond formation reaction has been proved to be carried out well under visible light irradiation, indicating the low-cost organic synthesis process. Further analysis confirmed the stability and general application of our heterogeneous Au nano-heterojunction catalyst.

Current studies focused on the effects of all-trans-retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were extracted aseptically from the quadriceps femoris of the knee joint of rats, and then incubated in medium containing 10% neonate bovine serum for 24 h adaptive culture. We first measured variations of correlation factors in synovium at 24, 48, 72, 96 and 120 h in control medium or in medium containing 20 ng/mL tumor necrosis factor alpha (TNF-α) (TNF-α-experiment). Then, we investigated the synovium exposed to three ATRA concentrations after 48 h incubation (ATRA-experiment). The effects of ATRA on synovitis were evaluated by observing the expression of inflammatory cytokines, angiogenic factors and the production of proteases in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and apoptosis and autophagy. In TNF-α-experiment, the secretion of nitric oxide (NO), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) increased significantly after TNF-α stimulation without pathological damage to the synovium. Hence, we successfully obtained the synovial explants model, which had longer inflammatory response time. In the ATRA-experiment, ATRA suppressed the secretion of IL-6 and NO, downregulated the NF-κB P65 and Bcl-2, increased levels of autophagy marker protein LC3, but different doses of ATRA showed inconsistent regulatory effects on VEGF and MMP-9. In short, ATRA inhibited TNF-α induced synovitis by the regulation of inflammatory cytokines and inhibiting NF-κB signal transduction and potentially promoting autophagy, apoptosis and angiogenesis, displaying its role in alleviating synovial inflammation in patients with RA.

A new aromatic diamine, 10,10-bis[4-(4-aminophenoxy)phenyl]-9(10 H)-anthrone (BAPA) has been synthesized from anthrone via three-step procedure. Direct phosphorylation polycondensation of BAPA with various aromatic dicarboxylic acids produced a series of cardo poly(ether amide)s with inherent viscosities of 0.97–1.29 dL g−1. All the polymers were readily soluble in polar solvents such as N-methyl-2-pyrrolidone, N, N-dimethylacetamide (DMAc), and pyridine at room temperature, and afforded transparent, strong, and flexible films upon casting from DMAc solvent. The resulting poly(ether amide)s had glass transition temperatures of 254–316°C, 10% weight loss temperatures of 495–524°C, and char yields of 55–70% at 800°C in nitrogen. These polymers were amorphous and their films exhibited tensile strengths of 81.6–104.7 MPa, tensile moduli of 1.8–2.4 GPa, and elongations at break of 8–15%.

Primary fallopian tube cancer (PFTC) shares the same diagnostic and management guidelines with epithelial ovarian cancer (EOC). The LION trail raised concerns regarding the role of systematic pelvic and para-aortic lymphadenectomy during debulking surgery. We aimed to evaluate the significance of lymphadenectomy in PFTC survival.This retrospective study analyzed the clinical features and survival of patients with PFTC who underwent primary surgery in our center between January 2013 and October 2020.Sixty-one patients diagnosed with PFTC were included in the study. Twenty-five (41.0%, 25/61) were diagnosed with FIGO (International Federation of Gynecology and Obstetrics) stages I/II and 36 (59.0%, 36/61) were diagnosed with stage III/IV. Twenty-nine (47.5%, 29/61) underwent pelvic lymphadenectomy with or without para-aortic lymphadenectomy, among which 12 (41.4%, 12/29) had lymph node metastasis confirmed by postoperative pathology. The mean progression-free survival was 60.4 months in the lymphadenectomy group and 37.8 months in the no-lymphadenectomy group (PFTC is often diagnosed earlier and has a better prognosis than EOC. Most patients with PFTC would benefit from lymphadenectomy. However, the extent to which this association translates to a more diverse population needs to be further identified.

The internal circadian rhythm is controlled by the central pacemaker in the hypothalamic suprachiasmatic nucleus (SCN). SCN drives coherent and synchronized circadian oscillations via intercellular coupling, which are resistant to environmental perturbations. Here we report that primary cilium is a critical device for intercellular coupling among SCN neurons and acts as a gatekeeper to maintain the internal clock in mice. A subset of SCN neurons, namely neuromedin S-producing (NMS) neurons, exhibit cilia dynamics with a pronounced circadian rhythmicity. Genetic ablation of ciliogenesis in NMS neurons enables a rapid phase shift of the internal clock under experimental jet lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lose their coherence following external perturbations. Rhythmic cilia dynamics drive oscillations of Sonic Hedgehog (Shh) signaling and oscillated expressions of multiple circadian genes in SCN neurons. Genetic and chemical inactivation of Shh signaling in NMS neurons phenocopies the effect of cilia ablation. Our findings establish ciliary signaling as a novel interneuronal coupling mechanism in the SCN and may lead to novel therapy of circadian disruption-linked diseases.One-Sentence SummaryRhythmic cilium is a critical device for intercellular coupling among SCN neurons and acts as gatekeeper for the internal clock.

Sorafenib is currently used to treat hepatocellular carcinoma (HCC). However, the development of chemoresistance to sorafenib is a major limitation for sorafenib-based therapy in patients with HCC. In the present study, the effect of the combination therapy of sorafenib and wh-4 on the proliferation of liver cancer cells was investigated. The results showed that sorafenib with wh-4 additively suppressed the proliferation of liver cancer cells. The colony formation of liver cancer cells decreased significantly in response to the combination treatment of sorafenib with wh-4, and it also induced the apoptosis of liver cancer cells. Western blot analysis demonstrated decreased expression of Bcl2, and increased expression of Bax in liver cancer cells treated with a combination of sorafenib and wh-4. Moreover, the migration of liver cancer cells was inhibited. The combination treatment of sorafenib with wh-4 reduced the expression levels of

N6-methyladenosine (m6A) is the most abundant chemical modification on mRNA and plays significant roles in many bioprocesses. However, the functions of m6A on cervical cancer (CC) tumorigenesis remain unclear. Here we found methyltransferase-like 3 (METTL3), a core member of the m6A methyltransferase family, was greatly upregulated as an independent prognostic factor in CC. Mechanistically, the transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. Functionally, we verified that METTL3 promoted proliferation and metastasis of CC cells by regulating of TXNDC5 expression through in vitro and in vivo experiments. In addition, our study verified the effect of METTL3/TXNDC5 axis on ER stress. Taken together, METTL3 facilitates the malignant progression of CC, suggesting that METTL3 might be a potential prognostic biomarker and therapeutic target for CC.

In this study, three new compounds, roxburic acid A (1) and two flavone glycosides isorhamnetin-3-O-α-L-rhamnosyl-(1→6)-β-D-glucopyranose-(1→3)-β-D-glucopyranoside (2), and kaempferol-7-O-β-D-glucopyranosyl-(1→3)-β-D-glucopyranoside (3) were isolated from an ethanol extract of the fresh Anoectochilus roxburghii (Wall.) Lindl., together with 10 known compounds (4-13). The structures of these compounds were comprehensively characterized by HR-ESI-MS, 1H NMR, 13C NMR, and 2 D-NMR. The DPPH free radical scavenging activity of the isolated compounds was evaluated, and the results showed that kaempferol-7-O-β-D-glucopyranosyl- (1→3) -β-D-glucopyranoside (3) and rutin (11) has the potential antioxidant activity with IC50 values of 139 μg/mL and 22.5 μg/mL respectively.

Candida auris is an opportunistic pathogen with multiple drug resistance. Therefore, researchers conducted a meta-analysis to review PCR's ability to diagnose Candida auris to promote the development of accurate Candida auris diagnosis.Researchers systematically retrieved relevant articles from PubMed, Cochrane Library, Embase, and Web of Science. Then, researchers extracted the key data required for the study from the selected articles. Meta-DiSc 1.4 was used for the statistical analysis. RevMan 5.3 was employed to assess the quality of the included literature. A funnel plot can appraise whether the included articles have publication bias.Five articles were included in the study. The results suggest that the pooled sensitivity and pooled specificity were 0.94 (95% CI: 0.92 - 0.95) and 0.99 (95% CI: 0.99 - 0.99), respectively. The positive and negative likelyhood ratios were 100.94 (95% CI: 47.51 - 214.47) and 0.07 (95% CI: 0.05 - 0.10), respectively. The diagnostic odds ratio was 1,814.70 (95% CI: 717.30 - 4,591.04), and the area under the SROC curve was 0.9935. Deek's funnel plot indicated that there was no publication bias.The results of the analysis indicate that PCR can become a valuable technique for the clinical diagnosis of Candida auris due to its excellent performance.

Chronic hepatitis B (CHB) virus infection is one of the leading causes of cirrhosis and liver cancer. Although the major drugs against CHB including nucleos(t)ide analogs and PEG-interferon can effectively control human hepatitis B virus (HBV) infection, complete cure of HBV infection is quite rare. Targeting host factors involved in the viral life cycle contributes to developing innovative therapeutic strategies to improve HBV clearance. In this study, we found that the mRNA and protein levels of SIRT2, a class III histone deacetylase, were significantly upregulated in CHB patients, and that SIRT2 protein level was positively correlated with HBV viral load, HBsAg/HBeAg levels, HBcrAg, and ALT/AST levels. Functional analysis confirmed that ectopic SIRT2 overexpression markedly increased total HBV RNAs, 3.5-kb RNA and HBV core DNA in HBV-infected HepG2-Na+/taurocholate cotransporting polypeptide cells and primary human hepatocytes. In contrast, SIRT2 silencing inhibited HBV transcription and replication. In addition, we found a positive correlation between SIRT2 expression and HBV RNAs synthesis as well as HBV covalently closed circular DNA transcriptional activity. A mechanistic study suggested that SIRT2 enhances the activities of HBV enhancer I/HBx promoter (EnI/Xp) and enhancer II/HBc promoter (EnII/Cp) by targeting the transcription factor p53. The levels of HBV EnI/Xp and EnII/Cp-bound p53 were modulated by SIRT2. Both the mutation of p53 binding sites in EnI/Xp and EnII/Cp as well as overexpression of p53 abolished the effect of SIRT2 on HBV transcription and replication. In conclusion, our study reveals that, in terms of host factors, a SIRT2-targeted program might be a more effective therapeutic strategy for HBV infection.

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110–CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110–CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.

Beam-steering devices, which are at the heart of optical wireless broadcasting communication links, play an important role in data allocation and exchange. An ideal beam-steering device features large steering angles, arbitrary channel numbers, reconfigurability, and ultra-compactness. However, these criteria have been achieved only partially with conventional beam-steering devices based on waveguides, micro-electrical mechanical systems, spatial light modulators, and gratings, which would substantially limit the application of optical wireless broadcasting communication techniques. In this study, we designed and experimentally demonstrated an ultra-compact full-duplex meta-broadcasting communication system, which exhibits beam steering angles up to ±40°, 14 broadcasting channels with capacity for downstream and upstream links up to 100 and 10 Gbps for each user channel, three operating modes for flexible signal switching, and meta-device dimensions as small as 2 mm × 2 mm. In particular, the beam-steering meta-devices are mass-manufactured by a complementary metal-oxide-semiconductor processing platform, which shows their potential for large-scale commercial applications. The demonstrated meta-broadcasting communication system merges optical wireless broadcasting communications and metasurfaces, which reduces the complexity of beam-steering devices while significantly increasing their performance, opening up a new avenue for high-quality optical wireless broadcasting communications. This article is protected by copyright. All rights reserved.

Cyclic GMP‐AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase‐activating protein‐(SH3 domain)–binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid‐phase condensation state. Using high‐resolution microscopy, we show that in resting cells, cGAS exhibits particle‐like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre‐condensed cGAS undergoes liquid–liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA‐induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA – but not RNA – treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.

Objective To evaluate the effects of antiretroviral therapy(ART)for the prevention of mother-to-child transmission(PMTCT)of acquired immune deficiency syndrome(AIDS)on the growth and development of 18-month-old children born by human immunodeficiency virus(HIV)-positive pregnant women in Lingshan County,Guangxi Zhuang Autonomous Region,and provide scientific evidence for improving the ART medication plan for PMTCT.Methods Lingshan County,ranking the first in the HIV-epidemic counties of Guangxi,was selected as the research site.According to the design of retrospective case-control study,we assigned all the subjects into the case group and the control group:(1)The case group included the HIV-positive pregnant women who had received ART for PMTCT and their HIV-negative infants in Lingshan County from 2010 to 2017.The historical cards and PMTCT data of them were collected from the national PMTCT database.(2)The control group included the healthy pregnant women and their healthy babies born in the Lingshan Maternity and Infant Hospital in 2017,and the children's growth and development data were collected.The stunted growth in children was defined as at least one of the three main indicators of body height,body weight,and head circumference below the normal range.Results The number of HIV-positive mothers and their infants in the case group was 391 and 368,respectively,and 87.21%(341/391)and 95.38%(351/368)of mothers and infants respectively received ART medication.The HIV positive rate,mortality rate,and mother-to-child transmission rate of 18-month-old children were 1.36%(5/368),4.35%(16/368),and 2.01%(5/249),respectively.The incidence of stunted growth of 18-month-old children in the case group and the control group was 42.12%(155/368)and 23.06%(101/438),respectively,with significant difference(