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Background PFI-3 is a small-molecule inhibitor that targets the bromodomains (BRDs) of Brahma-related gene 1 (BRG1). This monomeric compound, which has high selectivity and potent cellular effects, has recently been developed. Although PFI-3 has been reported as a potential therapeutic agent targeting thrombomodulin, its role in the regulation of vascular function remains unknown. Therefore, we aimed to investigate the impact of PFI-3 on arterial vessel tone. Methods A microvascular tension measurement device (DMT) was utilized to identify alterations in vascular tension within the mesenteric artery. To detect variations in cytosolic [Ca2+]i, a Fluo-3/AM fluorescent probe and fluorescence microscope were employed. Additionally, whole-cell patch clamp techniques were utilized to evaluate the activity of L-type voltage-dependent calcium channels (VDCCs) in cultured arterial smooth muscle cells (A10 cells). Results PFI-3 exerted a dose-dependent relaxation effect on rat mesenteric arteries with both intact and denuded endothelium after phenylephrine (PE)- and high-K+-induced constriction. PFI-3-induced vasorelaxation was not affected by the presence of L-NAME/ODQ or K+ channel blockers (Gli/TEA). PFI-3 abolished Ca2+-induced contraction on endothelium-denuded mesenteric arteries preincubated by PE in Ca2+-free solution. Incubation with TG had no impact on PFI-3-induced vasorelaxation pre-contracted by PE. PFI-3 reduced Ca2+-induced contraction on endothelium-denuded mesenteric arteries pre-incubated by KCl (60 mM) in Ca2+-free solution. PFI-3 declined extracellular calcium influx in A10 cells detected by Fluo-3/AM fluorescent probe and fluorescence microscope. Furthermore, we observed that PFI-3 decreased the current densities of L-type VDCC by whole-cell patch clamp techniques. Conclusions PFI-3 blunted PE and high K+-induced vasoconstriction independent of endothelium on rat mesenteric artery. The vasodilatory effect of PFI-3 may be attributed to its inhibition of VDCCs and receptor-operated calcium channels (ROCCs) on vascular smooth muscle cells (VSMCs).

In the article, olivine-structured pure LiNiPO4 and yttrium-doped LiNiPO4 powder were prepared by sol-gel method using citric acid as chelating agent. The effect of 1.0 mol% Y doping on the structure and electrochemical properties of LiNiPO4 materials using powder X-ray diffraction pattern, scanning electron microscope, cyclic voltammetry, and electrochemical impedance spectroscopy was investigated. It was found that 1.0 mol% Y doping could induce an increase in lattice parameters and a decrease in particle sizes, which could enlarge lithium-ion diffusion channel, increase carriers concentration, and shorten diffusion lengths, thus decreasing polarization and improving lithium-ion diffusion and conductivity. All those could result in enhanced redox peak current density, decreased charge-transfer resistance, and potential separation between oxidation peak and reduction peak. Y doping could also decrease the highest occupied molecular orbital (HOMO) of NiO6 octahedron caused by Jahn-Teller effect, which caused the raises of redox potential.

Background Superficial CD34-positive fibroblastoma (SCPFT) is a newly discovered mesenchymal tumor characterized by high polymorphism, low mitotic rate, and diffuse CD34-positive reactions. Aim To further determine the clinicopathological features of SCPFT. Methods We retrospectively analyzed the clinicopathological data, immunohistochemistry results, and differential diagnoses of four patients with SCPFT and performed a literature review. Relevant fusion genes were also detected. Results The tumors were all located in the lower extremities and presented as slow-growing painless masses located in the dermis and subcutaneous tissue. Microscopically, the tumors were composed of spindle-shaped to epithelioid cells with scattered abnormal and pleomorphic nuclei on a fibrous or fibromyxoid background. Necrosis was not found in the tumor tissues, and mitotic figures were rare. Immunohistochemically, the tumor cells were strongly positive for vimentin and CD34, and CKpan showed focal positivity in two tumors. All four patients were followed (13-57 mo, mean 35 mo), and one patient experienced local recurrence. Conclusion SCPFT is a newly discovered borderline mesenchymal tumor that can locally recur or even metastasize. Familiarity with its clinicopathological features will help avoid confusion with skin mesenchymal tumors with similar features.

We combined viral genome sequencing with contact tracing to investigate introduction and evolution of severe acute respiratory syndrome coronavirus 2 lineages in Santa Clara County, California, from 27 January to 21 March 2020. From 558 persons with coronavirus disease 2019, 101 genomes from 143 available clinical samples comprised 17 lineages, including SCC1 (n = 41), WA1 (n = 9; including the first 2 reported deaths in the United States, with postmortem diagnosis), D614G (n = 4), ancestral Wuhan Hu-1 (n = 21), and 13 others (n = 26). Public health intervention may have curtailed the persistence of lineages that appeared transiently during February and March. By August, only D614G lineages introduced after 21 March were circulating in Santa Clara County.

Polymeric monoliths are of great interest in a variety of applications. A new gelation approach to produce a mechanically stable polystyrene (PS) gel directly from its microemulsion is reported. To produce a PS gel, the as-prepared microemulsion is first demulsified by adding selected water-miscible organic solvents. The small PS latex particles liberated from the surfactant are assembled into a piece of bulk material at an appropriate temperature with a high degree of entanglement of the polymer chains. It is found that the d2T/η value is an important parameter to evaluate the gelation ability of the organic solvents and helps determine the gelation conditions. Finally, PS monoliths are obtained by capillary drying and their pore structures can be effectively tuned by changing the gelation time and the amount of solvent exchanged with water. This allows the controlled preparation of bulk PS artefacts with densities in the range of 0.06 to 1.14 g cm−3. This simple method of PS monolith production avoids the use of shaping tools or chemical templates, needs less energy, and is a promising alternative approach to design either integrated porous or compact polymer materials.

In this work, the synthesized Co3O4/NiCo2O4/CC is a layered structure, which was prepared by a feasible method of hydrothermal reaction, thermal annealing of ZIF-67 template and other thermal treatment. This novel structure is based on carbon cloth, and Co3O4 hollow nanocubes as semiconductor material grow in situ on nanowire arrays. Under the condition of different temperatures and different concentrations of ethanol, the response of the gas sensor based on Co3O4/NiCo2O4 was studied. The result shows high sensitivity, good linear relationship and excellent response-recovery properties. And its high sensitivity is demonstrated with a maximum response up to 35 at 180 °C and 200 ppm. The sensor performs well in gas sensitivity thanks to the structure of the material. Large specific surface area, high porosity and fast electronic transport channel between Co3O4 and CC are all important reasons. Accordingly, this method of preparing the novel hierarchical structure can improve the gas sensitive performance. This work would provide a reference for further research on the application of Co3O4 MOF-derived structure in gas sensitive.

Coronary computed tomography angiography (CCTA) is affected by calcification artifacts, which reduces its diagnostic efficacy. CT-derived fractional flow reserve (CTFFR) based on CCTA has been proven to be accurate in the diagnosis of non-calcified patients, but its clinical use in patients with calcified coronary artery disease remains to be investigated. The purpose of this study was to determine the effect of coronary artery calcification on CTFFR.CCTA, coronary angiography, and FFR were performed on 128 patients in three clinical medical centers. Local investigators performed an assessment of stenosis for CCTA and the core laboratory performed the CTFFR calculations. CTFFR ≤0.8 and diameter stenosis ≥50% for CCTA was identified as lesion-specific ischemia. The diagnostic performance of CTFFR in identifying the diagnostic sensitivity, specificity, and accuracy was analyzed using an invasive FFR ≤0.8 as the gold standard. We compared the diagnostic performances between CTFFR and CCTA according to the level of calcification. We divided patients into four groups based on the coronary artery calcification score [coronary artery calcification score (CACS) =0,0 to100, ≥100 to400, and ≥400].The Youden index indicated an optimal threshold of 0.80 for CTFFR to identify functionally ischemic lesions. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under receiver operating characteristic curve (AUC) for CTFFR on a per-patient basis were 90% (80-96%), 98% (92-99%), 94% (89-97%), 98% (91-99%), 92% (83-97%), and 96.9% (94.2-99.6%), respectively. Compared to CCTA, CTFFR had a higher specificity, accuracy, PPV, NPV, and AUC in both the low to intermediate calcification group and the high calcification group. The diagnostic efficacy of CTFFR was higher than that of CCTA without the influence of calcification.This Chinese multi-center study showed that CTFFR based on novel computational fluid dynamics (CFD) modeling demonstrated very high diagnostic efficacy compared to the invasive measurement of FFR in all lesions suspected coronary artery disease (CAD). Of particular note are the high specificity, sensitivity, and accuracy of CTFFR, even in patients with calcification, which were significantly better than previous CCTA assessments.

Nanomedicines (NMs) have emerged as an efficient approach for developing novel treatment strategies against a variety of diseases. Over the past few decades, NM formulations have received great attention, and a large number of studies have been performed in this field. Despite this, only about 60 nano-formulations have received industrial acceptance and are currently available for clinical use. Their in vivo pharmaceutical behavior is considered one of the main challenges and hurdles for the effective clinical translation of NMs, because it is difficult to monitor the pharmaceutic fate of NMs in the biological environment using conventional pharmaceutical evaluations. In this context, non-invasive imaging modalities offer attractive solutions, providing the direct monitoring and quantification of the pharmacokinetic and pharmacodynamic behavior of labeled NMs in a real-time manner. Imaging evaluations have great potential for revealing the relationship between the physicochemical properties of NMs and their pharmaceutical profiles in living subjects. In this review, we introduced imaging techniques that can be used for in vivo NM evaluations. We also provided an overview of various studies on the influence of key parameters on the in vivo pharmaceutical behavior of NMs that had been visualized in a non-invasive and real-time manner. Graphical Abstract

Kallmann syndrome (KS) is a congenital disorder characterized by idiopathic hypogonadotropic hypogonadism and olfactory dysfunction. KS is linked to variants in >34 genes, which are scattered across the human genome and show disparate biological functions. Although the genetic basis of KS is well studied, the mechanisms by which disruptions of these diverse genes cause the same outcome of KS are not fully understood. Here we show that disruptions of KS-linked genes affect the same biological processes, indicating convergent molecular mechanisms underlying KS. We carried out machine learning-based predictions and found that KS-linked mutations in heparan sulfate 6-O-sulfotransferase 1 (HS6ST1) are likely loss-of-function mutations. We next disrupted Hs6st1 and another KS-linked gene, fibroblast growth factor receptor 1 (Fgfr1), in mouse neuronal cells and measured transcriptome changes using RNA sequencing. We found that disruptions of Hs6st1 and Fgfr1 altered genes in the same biological processes, including the upregulation of genes in extracellular pathways and the downregulation of genes in chromatin pathways. Moreover, we performed genomics and bioinformatics analyses and found that Hs6st1 and Fgfr1 regulate gene transcription likely via the transcription factor Sox9/Sox10 and the chromatin regulator Chd7, which are also associated with KS. Together, our results demonstrate how different KS-linked genes work coordinately in a convergent signaling pathway to regulate the same biological processes, thus providing new insights into KS.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) facilitates CD4This study recruited 73 AS patients underwent adalimumab treatment. Peripheral blood mononuclear cell (PBMC) was obtained at Week (W) 0, W4, W8, and W12 after treatment initiation; then, MALT1 was measured using RT-qPCR. Furthermore, PBMC and serum at W0 were proposed to flow cytometry and ELISA for Th1 cells, Th17 cells, IFN-γ, and IL-17A levels measurement. Besides, 20 osteoarthritis patients and 20 healthy controls (HCs) were enrolled to detect MALT1.Mucosa-associated lymphoid tissue lymphoma translocation protein 1 expression was higher in AS patients compared with HCs (p 0.001) and osteoarthritis patients (p 0.001). Besides, MALT1 expression was positively linked with CRP (p = 0.002), BASDAI (p = 0.026), PGADA (p = 0.040), ASDASMucosa-associated lymphoid tissue lymphoma translocation protein 1 positively correlates with Th17 cells, inflammatory, and activity degree; meanwhile, its decrement along with treatment reflects the response to TNF inhibitor in AS patients.

Background Coffin-Siris syndrome (CSS) is a rare autosomal dominant disorder characterized by intellectual disability, developmental delay, and characteristic facial features. Few patients with cutaneous phenotype in this rare syndrome have been reported. Case presentation Herein, we describe a 12-year-old Chinese girl diagnosed with CSS, who was referred to our hospital because of intellectual disability and short stature. Prominent characteristics of the cutaneous system were observed: (1) A congenital giant nevus from the left frontal and temporal regions to the entire left scalp; and (2) multiple melanocytic nevi on the face and trunk. Whole exome sequencing revealed a novel heterozygous variant in the ARID1B gene. Recombinant human growth hormone (rhGH) was given for short stature, and resulted in significantly improved height. No enlargement or malignant transformation of nevi occurred within 4 years of follow-up. Conclusion The symptoms in cutaneous system is noteworthy,which may be a neglected phenotype in CSS.The therapeutic response of growth hormone is effective in this patient and no tumor related signs were found.

2D lamellar materials can offer high surface area and abundant reactive sites, thus showing an appealing prospect in photocatalytic hydrogen evolution. However, it is still difficult to build cost-efficient photocatalytic hydrogen evolution systems based on 2D materials. Herein, an in situ growth method is employed to build 2D/2D heterojunctions, with which 2D Ni-based metal-organic layers (Ni-MOLs) are closely grown on 2D porous CdS (P-CdS) nanosheets, affording traditional P-CdS/Ni-MOL heterojunction materials. Impressively, the optimized P-CdS/Ni-MOL catalyst exhibits superior photocatalytic hydrogen evolution performance, with an H

Zeolite supported amorphous metal oxide nanolayers with high specific surface area, abundant adsorption sites, and excellent reusability hold a bright prospect in the efficient removal of contaminants, yet it is proven to be still challenging to precisely regulate and control their synthesis. Herein, we reported a facile synthetic strategy for rational design and achieving the uniform and firm

Methane Hydrates is an ice-like crystalline substance formed by methane and water under high pressure and low temperature environment. Each 1 unit methane hydrates contains about 170 units (converted in standard conditions) of methane gas. The low temperature and high pressure environment in deep water leads to the existence of hydrate layer in the shallow formation, which poses a significant challenge to cementing. The conventional cement slurry systems have limitations when applied in such well condition, since the heat of hydration during cement setting is high and there is a high risk of gas liberation from methane hydrates, easily causing severe well security issues. The low temperature environment, unconsolidated formation and narrow safety window also increased the complexity of the cementing jobs by a high performance requirement of the cement slurry. A low hydration heat cement slurry and an indoor cementing simulation evaluation method were developed in order to ensure effective isolation of the hydrate layer. This paper will describe in detail about the cement slurry development, performance and evaluation process in the lab with a novel method in the industry. This technology was proven as a solution for deep water hydrate layer well cementing, which is a great reference for cementing industry.

A field trial was conducted to identify the key factors affecting intraspecific variation in the cadmium (Cd) content in the grain of winter wheat. Three wheat cultivars with low Cd accumulation and two wheat cultivars with high Cd accumulation were planted. The Cd accumulation and transport and ionomic traits were examined in different organs of the tested wheat cultivars. Additionally, correlation analysis and principal component analysis were used to identify the key plant organs, translocation pathways, and elements that determine the intraspecific variation in the Cd content in wheat grain. The results showed that the bioaccumulation factors of Cd in glume, rachis, internode 1, and node 1, as well as the transport factors of Cd from rachis to grain, from rachis to glume, from internode 1 to rachis, and from node 1 to internode 1, were significantly correlated with Cd bioaccumulation factors in grain. The above-mentioned bioaccumulation factors and transport factors of Cd made a great contribution to the principal components that could discriminate between the wheat cultivars with low and high Cd accumulation and were significantly different among cultivars. Therefore, glume, rachis, internode 1, and node 1 were the key organs affecting the genotype differences in Cd content in wheat grain, and Cd translocation from rachis to grain, from rachis to glume, from internode 1 to rachis, and from node 1 to internode 1 were the key pathways controlling the variety differences in Cd accumulation in wheat grain. The analysis of wheat ionome showed that the bioaccumulation factors of Mg and Mn in the key organs and the transport factors of Mo, Cr, and Pb in the key transport pathways were significantly correlated with the bioaccumulation factor of Cd in wheat grain and contributed greatly to the differentiation between the wheat cultivars with low and high Cd accumulation in the principal component analyses. Thus, in the above-mentioned key organs and transport pathways, Mg, Mn, Mo, Cr, and Pb were the key elements affecting the genotype differences in Cd content in wheat grain.

To assess transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a detention facility experiencing a coronavirus disease outbreak and evaluate testing strategies, we conducted a prospective cohort investigation in a facility in Louisiana, USA. We conducted SARS-CoV-2 testing for detained persons in 6 quarantined dormitories at various time points. Of 143 persons, 53 were positive at the initial test, and an additional 58 persons were positive at later time points (cumulative incidence 78%). In 1 dormitory, all 45 detained persons initially were negative; 18 days later, 40 (89%) were positive. Among persons who were SARS-CoV-2 positive, 47% (52/111) were asymptomatic at the time of specimen collection; 14 had replication-competent virus isolated. Serial SARS-CoV-2 testing might help interrupt transmission through medical isolation and quarantine. Testing in correctional and detention facilities will be most effective when initiated early in an outbreak, inclusive of all exposed persons, and paired with infection prevention and control.

Great progress has been made in the development of cathode materials for Al-metal batteries. However, the in-depth study of Al anodes, especially the battery instability caused by Al dendrite growth, has not received much attention. In this work, we have identified the in-situ formation of Al dendrite growth, which is proved to bottleneck the practical use of Al-metal batteries. The dendrite formation severely affects battery performance, such as voltage and efficiency fluctuations, unstable cycling, etc. To further demonstrate the detailed growing process of dendrites, we make a comprehensive investigation into the interfacial chemistry of Al anode. We have found that the naturally formed Al2O3 surface film is dissolved in the ionic liquid electrolyte during Al plating, accompanied by the formation of solid-electrolyte interphase containing Al-Cl and Al-O like species on the anode surface before dendrite growth. To suppress this dendrite growth, we propose the use of porous Al, which provides a homogeneous ion flux and decreases the local current density. As a result, the porous anode maintains stable cycling over a wide range of current densities and areal capacities. The Al-graphite battery shows stable cycling up to 18000 times without capacity decay. This work suggests the significance of suppressing dendrite growth for the real applications and commercialization of Al-metal batteries and will draw attention to the battery design from the anode side.

g-C3N4/TiO2 heterojunction functional foams were constructed as gas purification filters for treating NO indoor gas with a high removal rate (>65%) and high stability under visible-light (λ ≥ 400 nm) illumination. The skeletons of the 3D foams consisted of g-C3N4 and TiO2 quantum dots (QDs). Such 3D porous foamy filters provided a large surface area and continuous pores for trapping and oxidizing NO molecules owing to their excellent adsorption and activation capability. The embedded g-C3N4/TiO2 QD heterojunctions in the foam skeletons effectively promoted the separation of photo-generated carriers, allowing the generation of more active species (holes and ˙OH) for oxidizing NO molecules. An oxidation pathway (NO → NO+ → NO2− or NO3−) was proposed based on in situ FTIR spectroscopy, which suggested the important role of NO+ for removing NO gas. This work provides an efficient and stable air-purification filter for indoor air treatment.

In order to maintain the thermal stability of SOT devices with nanoscale size, it is desirable to achieve current induced magnetic switching in magnetic materials with high perpendicular anisotropy. In the present paper, current induced field-free switching of FePt/[TiN/NiFe]5 is achieved by interlayer exchange coupling, in which in-plane magnetized NiFe serves as a coupling layer through a TiN space layer. The large Ku (1.03 × 107 erg cc−1) and low critical current density values (0.17 × 107 A cm−2) show great advantages in thermal stability and energy consumption. Interestingly, it is found that the rotation directions of the current-induced magnetic switching loops under different applied magnetic fields are dependent on the sputtering temperature of [TiN/NiFe]5 multilayers: once sign change for FePt/[TiN/NiFe]5 RT and three sign changes for FePt/[TiN/NiFe]5 HT. Simultaneously, when the magnetization direction of NiFe changes from the Hx direction to −Hx direction, the switching polarities at Hx = 0 always remain unchanged, which is different from other groups’ reports. These phenomena may be attributed to the combined effect of TiN layer thickness induced ferromagnetic or antiferromagnetic coupling and the inherent Hin. Furthermore, gradual tuning of resistance states through the trains of current pulses has also been realized, showing potential applications in artificial synaptic networks. These results will put forward the applications of L10-FePt in current controlled MRAM and neuromorphic computing.