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A novel type of phosphorus doped Ti3C2Tx MXene nanosheets (P-Ti3C2Tx) is synthesized via a facile and controllable strategy of annealing MXene nanosheets with the presence of sodium hypophosphite. A combination of theoretical density functional theory calculation and experimental X-ray photoelectron spectroscopy discloses that the doped P atoms are prone to fill into Ti vacancies first due to their lowest formation free energy (ΔGP* = −0.028 eV·A−2) and next to bond with surface terminals on MXene layers (ΔGP* = 0.013 eV·A−2), forming P-C and P-O species, respectively. More importantly, the as-obtained P-Ti3C2Tx is, for the first time, investigated as the electrode material for supercapacitors, demonstrating a significantly boosted electrochemical performance by P doping. As a result, P-Ti3C2Tx electrode delivers a high specific capacitance of 320 F·g−1 at a current density of 0.5 A·g−1 (much higher than 131 F·g−1 for undoped MXene), an ultrahigh rate retention of 83.8% capacitance at 30 A·g−1, and a high cycling stability over continuous 5000 cycles.

Excited state intramolecular proton transfer (ESIPT) has drawn much attention for its important applications in a variety of areas. Here, the steady-state and time-resolved absorption spectroscopic experiments as well as DFT/TD-DFT calculations are employed to study the photophysical properties and photochemical reaction mechanisms of 2-(2'-hydroxyphenyl) benzoxazole (HBO) and selected derivatives (compounds 1-3). Because of their larger π-conjugation framework, compounds 1-3 display red-shifted absorbance but blue-shifted fluorescence compared with HBO. A fast ESIPT process is observed directly for HBO while compound 3 has an enol/keto equilibrium type of ESIPT that exhibits dual emission. Interestingly, only the emission of the enol form is observed for compounds 1 and 2 which suggests that the ESIPT process is strongly inhibited. These results indicate the decoration with electron-withdrawing groups such as thiadiazol and pyrazine on the hydroxyphenyl ring (compounds 1 and 2) apparently suppresses the proton-transfer processes in their excited states. Whereas the ESIPT process is rarely increased for compound 3 that modified with the phenanthrol ring, because the effective conjugation is reduced for compound 3 compared with HBO. The work here provides fundamental insights that may be useful for designing novel ESIPT molecules in the future.

Newly designed push-pull ligands (L1 and L2) with bithiophene (bth) as a donor and phenazine (phz) or quinoxalino[2,3-b]quinoxaline (qxq) as acceptors were synthesized and also incorporated with a bipyridyl Ru(II) complex to give Ru1 and Ru2, respectively. The ultrafast photophysical dynamics of the ligand and their respective Ru(II) complexes were well-characterized using time-resolved spectroscopies and quantum chemical calculations. Photoinduced charger transfer (CT) and intersystem crossing (ISC) processes were directly observed for L1 and L2. In addition, the interplay of three different triplet excited states was directly observed in the related Ru(II) complexes. The lowest-lying triplet excited states of the ligands and their respective Ru(II) complexes were both attributed to the CT transitions from donor (bth) to acceptor (phz or qxq) and result in 3ICT (intramolecular charge transfer) and 3ILCT (intraligand charge transfer) excited states, respectively. The lifetimes of the lowest-lying triplet excited states of L1, L2, Ru1, and Ru2 were measured to be 21.3, 50.4, 2.75, and 4.16 μs, respectively.

Femtosecond laser flash photolysis of 3-(1a,9b-dihydro-1H-cyclopropa[l]phenanthren-1-ylidene)tetrahydrofuran produces singlet 3-oxacyclopentylidenecarbene which reacts with acetonitrile solvent to form an ylide. This is the first direct detection of ylide formation by an alkylidenecarbene. This new type of ylide was observed to have a broad absorption band in the visible region with λmax ∼450 nm and a lifetime of ∼13.5 ps. As with other "conventional" carbenes (the divalent carbon atom is separately bound to two substituents), this ylide formation method could be also useful for detecting alkylidenecarbenes, especially those that do not absorb at wavelengths suitable for direct observation. Furthermore, the mechanisms by which 3-oxacyclopentylidenecarbene forms the ylide and the overall favorability of ylide formation, vis-a-vis ring expansion of the carbene to strained 3-oxacyclohexyne, were supported by results from density functional theory calculations.

Background Stem cell-based regenerative therapy is a novel approach to severe damaged skin. Perinatal tissues such as placenta are considered as promising alternatives. The present study aimed to investigate the effect of insulin-like growth factor-1 (IGF-1)-expressing placenta-derived mesenchymal stem cells (hPMSCs) on healing of burn wounds. Materials and methods hPMSCs were isolated from human placenta, and IGF-1 was transducted into hPMSCs via lentivirus. Flow cytometry and MTT assay were performed to assess cell apoptosis and viability, respectively. Immunostaining of CK19 and ki67 was for evaluating epithelial differentiation ability and cell proliferation. For in vivo studies, we established a mouse model of scalding and performed local administration of IGF-1-expressing hPMSCs via subcutaneous injection. Wound histology was analyzed with H&E staining. The expression of fibrogenic cytokines was detected by western blot. The production of pro-inflammatory factors was measured by ELISA. Results Overexpression of IGF-1 promoted cell proliferation and epithelial differentiation of hPMSCs in vitro and in vivo. Mice with burn injury displayed increased wound contraction and healing rates following treatment with IGF-1-expressing hPMSCs. There was less inflammatory infiltration and reduced collagen disposition in the presence of IGF-1 at the wound site. Administration of IGF-1-expressing hPMSCs suppressed inflammation by decreasing the levels of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6. Besides, IGF-1 increased VEGF expression, and decreased TGF-β1, collagen I and collagen III expressions in vivo. Conclusions IGF-1-expressing PMSCs promotes cell proliferation and epithelial differentiation, inhibits inflammation and collagen deposition, and thus contributes to wound healing.

Acceleration of singlet-triplet intersystem crossings (ISC) is instrumental in bolstering triplet exciton harvesting of multi-resonance thermally activated delayed fluorescent (MR-TADF) emitters. This work describes a simple gold(I) coordination strategy to enhance the spin-orbit coupling of green and blue BN(O)-based MR-TADF emitters, which results in a notable increase in rate constants of the spectroscopically observed ISC process to 3×10

Phenotypic screening still plays an important role in discovering new drugs, especially for diseases with complex pathogenesis, such as diabetes. As excessive gluconeogenesis is considered an important factor in the occurrence of hyperglycemia in T2DM, we previously screened our compounds library for active molecules which inhibit gluconeogenesis, resulting in the discovery of SL010110 with a unique mechanism, different from metformin and a thienopyridine derivative (DMT). The SARs study of SL010110 led to the discovery of 10v. Compared with SL010110, 10v showed improved anti-gluconeogenesis potency and pyruvate tolerance. A further pharmacokinetic study demonstrated that 10v displayed a relatively short half-life, moderate volume of distribution, and moderate to high oral bioavailability. In vivo chronic experiments showed an improved capability of 10v in ameliorating hyperglycemia as the 5 mg/kg 10v treatment greatly reduced non-fasting and fasting blood glucose levels, making it a promising candidate for the treatment of T2DM. The progression from in vitro screening to in vivo testing of the derivatized compounds provided a useful phenotypic screening drug discovery strategy based on the inhibition of gluconeogenesis.

High maximum external quantum efficiency (EQE

Background The sensitivity to endocrine therapy assay (SET2,3) predicts treatment outcomes in Stage II-III breast cancer. SET2,3 measures transcription related to estrogen and progesterone receptors (SETER/PR index) and the molecular subtype (RNA4: ESR1, PGR, ERBB2, AURKA) from formalin-fixed paraffin-embedded (FFPE) tissue sections. Methods We designed a nested study across 3 pathology laboratories, each testing 60 breast cancers twice in controlled batches. Laboratories macrodissected and directly homogenized the unstained FFPE tumor sections, then performed the QuantiGene Plex bead-based hybridization assay. SET2,3 was calculated centrally using predefined statistical R-scripts and applying pre-defined cutpoints. Concordance correlation coefficient (CCC) was calculated from continuous measurements and Kappa statistic from categorical results. A mixed-effects model estimated contributions to bias (fixed effects) and variance (random effects) from the replicated design. Results Intralaboratory (CCC 0.96–0.99) and interlaboratory (CCC 0.98–0.99) SET2,3 results were concordant, with rates of agreement for high/low categorization within (Kappa 0.83–0.93) and between laboratories (Kappa 0.87–0.88). The relative contributions to overall variance of SET2,3 measurements were 96.90% from biological differences between cancers, 0.67% from interlaboratory variability, and 2.44% from residual causes including intralaboratory replicates. Similar results were obtained with SETER/PR, the baseline prognostic index calculated using pathological or clinical tumor and nodal staging information, and the 4 individual genes (ESR1, PGR, ERBB2, and AURKA). Conclusion Intra- and interpathology laboratory measurements of SET2,3 and its components were highly reproducible when tested from FFPE tumor sections.

Solid-state molecular motions (SSMM) play a critical role in adjusting behaviors and properties of materials. However, research on SSMM, especially for multicomponent systems, suffers from various problems and is rarely explored. Herein, through collaboration with cocrystal engineering, visualization and manipulation of SSMM in two-component systems, namely, FSBO ((E)-2-(4-fluorostyryl)benzo[d]oxazole)/TCB (1,2,4,5-tetracyanobenzene) and PVBO ((E)-2-(2-(pyridin-4-yl)vinyl)benzo[d]oxazole)/TCB, were realized. The obtained yellow-emissive F/T (FSBO/TCB) cocrystal displayed turn-on fluorescence, and the green-emissive P/T (PVBO/TCB) cocrystal presented redder emission, both of which exhibited an aggregation-induced emission property. At varied pressure and temperature, the grinding mixtures of FSBO/TCB and PVBO/TCB displayed different molecular motions that were readily observed through the fluorescence signal. Notably, even without grinding, FSBO and TCB molecules could move over for 4 mm in a 1D tube. The unique emission changes induced by SSMM were applied in information storage and dynamic anticounterfeiting. This work not only visualized and manipulated SSMM but offered more insights for multicomponent study in aggregate science.

HNO is a highly reactive molecule that shows promise in treating heart failure. Molecules that rapidly release HNO with precise spatial and temporal control are needed to investigate the biology of this signaling molecule. (Hydroxynaphthalen-2-yl)methyl-photocaged N-hydroxysulfonamides are a new class of photoactive HNO generators. Recently, it was shown that a (6-hydroxynaphthalen-2-yl)methyl (6,2-HNM)-photocaged derivative of N-hydroxysulfonamide incorporating the trifluoromethanesulfonamidoxy group (1) quantitatively generates HNO. Mechanistic studies have now been carried out on this system and reveal that the ground state protonation state plays a key role in whether concerted heterolytic C-O/N-S bond cleavage to release HNO occurs versus undesired O-N bond cleavage. N-Deprotonation of 1 can be achieved by adding an aqueous buffer or a carboxylate salt to an aprotic solvent. Evidence is presented for C-O/N-S bond heterolysis occurring directly from the singlet excited state of the N-deprotonated parent molecule on the picosecond time scale, using femtosecond time-resolved transient absorption spectroscopy, to give a carbocation and 1NO-. This is consistent with the observation of significant fluorescence quenching when HNO is generated. The carbocation intermediate reacts rapidly with nucleophiles including water, MeOH, or even (H)NO in the absence of a molecule that reacts rapidly with (H)NO to give an oxime.

BACKGROUND We proposed that a test for sensitivity to the adjuvant endocrine therapy component of treatment for patients with stage II-III breast cancer (SET2,3) should measure transcription related to estrogen and progesterone receptors (SETER/PR index) adjusted for a baseline prognostic index (BPI) combining clinical tumor and nodal stage with molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA). PATIENTS AND METHODS Patients with clinically high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer received neoadjuvant taxane-anthracycline chemotherapy, surgery with measurement of residual cancer burden (RCB), and then adjuvant endocrine therapy. SET2,3 was measured from pre-treatment tumor biopsies, evaluated first in an MD Anderson Cancer Center (MDACC) cohort (n = 307, 11 years' follow-up, U133A microarrays), cut point was determined, and then independent, blinded evaluation was carried out in the I-SPY2 trial (n = 268, high-risk MammaPrint result, 3.8 years' follow-up, Agilent-44K microarrays, NCI Clinical Trials ID: NCT01042379). Primary outcome measure was distant relapse-free survival. Multivariate Cox regression models tested prognostic independence of SET2,3 relative to RCB and other molecular prognostic signatures, and whether other prognostic signatures could substitute for SETER/PR or RNA4 components of SET2,3. RESULTS SET2,3 added independent prognostic information to RCB in the MDACC cohort: SET2,3 [hazard ratio (HR) 0.23, P = 0.004] and RCB (HR 1.77, P < 0.001); and the I-SPY2 trial: SET2,3 (HR 0.27, P = 0.031) and RCB (HR 1.68, P = 0.008). SET2,3 provided similar prognostic information irrespective of whether RCB-II or RCB-III after chemotherapy, and in both luminal subtypes. Conversely, RCB was most strongly prognostic in cancers with low SET2,3 status (MDACC P < 0.001, I-SPY2 P < 0.001). Other molecular signatures were not independently prognostic; they could effectively substitute for RNA4 subtype within the BPI component of SET2,3, but they could not effectively substitute for SETER/PR index. CONCLUSIONS SET2,3 added independent prognostic information to chemotherapy response (RCB) and baseline prognostic score or subtype. Approximately 40% of patients with clinically high-risk HR+/HER2- disease had high SET2,3 and could be considered for clinical trials of neoadjuvant endocrine-based treatment.

Background Our objective was to assess whether modifications to a customized targeted RNA sequencing (RNAseq) assay to include unique molecular identifiers (UMIs) that collapse read counts to their source mRNA counts would improve quantification of transcripts from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples. The assay (SET4) includes signatures that measure hormone receptor and PI3-kinase related transcriptional activity (SETER/PR and PI3Kges), and measures expression of selected activating point mutations and key breast cancer genes. Methods Modifications included steps to introduce eight nucleotides-long UMIs during reverse transcription (RT) in bulk solution, followed by polymerase chain reaction (PCR) of labeled cDNA in droplets, with optimization of the polymerase enzyme and reaction conditions. We used Lin’s concordance correlation coefficient (CCC) to measure concordance, including precision (Rho) and accuracy (Bias), and nonparametric tests (Wilcoxon, Levene’s) to compare the modified (NEW) SET4 assay to the original (OLD) SET4 assay and to whole transcriptome RNAseq using RNA from matched fresh frozen (FF) and FFPE samples from 12 primary breast cancers. Results The modified (NEW) SET4 assay measured single transcripts (pER/PR (p=0.002) more reproducibly in technical replicates from FFPE samples. The modified SET4 assay was more precise for measuring single transcripts (Rho 0.966 vs 0.888, pER/PR (Rho 0.985 vs 0.968) or PI3Kges (Rho 0.985 vs 0.946) in FFPE, compared to FF samples. It was also more precise than wtRNAseq of FFPE for measuring transcripts (Rho 0.986 vs 0.934, pER/PR (Rho 0.993 vs 0.915, p=0.004), but not PI3Kges (Rho 0.988 vs 0.945, p=0.051). Accuracy (Bias) was comparable between protocols. Two samples carried a PIK3CA mutation, and measurements of transcribed mutant allele fraction was similar in FF and FFPE samples and appeared more precise with the modified SET4 assay. Amplification efficiency (reads per UMI) was consistent in FF and FFPE samples, and close to the theoretically expected value, when the library size exceeded 400,000 aligned reads. Conclusions Modifications to the targeted RNAseq protocol for SET4 assay significantly increased the precision of UMI-based and reads-based measurements of individual transcripts, multi-gene signatures, and mutant transcript fraction, particularly with FFPE samples.

Defects have been observed in graphene and are expected to play a key role in its optical, electronic, and magnetic properties. However, because most of the studies focused on the structural characterization, the implications of topological defects on the physicochemical properties of graphene remain poorly understood. Here, we demonstrate a bottom-up synthesis of three novel nanographenes (1-3) with well-defined defects in which seven-five-seven (7-5-7)-membered rings were introduced to their sp2 carbon frameworks. From the X-ray crystallographic analysis, compound 1 adopts a nearly planar structure. Compound 2, with an additional five-membered ring compared to 1, possesses a slightly saddle-shaped geometry. Compound 3, which can be regarded as the "head-to-head" fusion of 1 with two bonds, features two saddles connected together. The resultant defective nanographenes 1-3 were well-investigated by UV-vis absorption, cyclic voltammetry, and time-resolved absorption spectra and further corroborated by density functional theory (DFT) calculations. Detailed experimental and theoretical investigations elucidate that these three nanographenes 1-3 exhibit an anti-aromatic character in their ground states and display a high stability under ambient conditions, which contrast with the reported unstable biradicaloid nanographenes that contain heptagons. Our work reported herein offers insights into the understanding of structure-related properties and enables the control of the electronic structures of expanded nanographenes with atomically precise defects.

Through this study, we aimed to evaluate the effects of different types of placenta previa (PP) on maternal and neonatal outcomes. This study was conducted in The Third Affiliated Hospital of Guangzhou Medical University and Tongji Hospital between January 2009 and 2019. PP was traditionally classified into four types, namely low-lying placenta, marginal, partial, and complete PP. Previous studies have classified PP into two types, namely low-lying placenta and PP. Based on our clinical experience, we proposed the classification of PP into three types, for the first time, which included low-lying placenta, “marpartial” (marginal and partial) PP, and complete PP. Multivariate logistic regression analysis was performed to determine the effects of different types of PP on maternal and neonatal outcomes. In total, 4490 singleton pregnancies were complicated with PP. In the four-classification method, compared with women with low-lying placenta, women with complete PP had a risk of placenta accrete spectrum disorders, postpartum hemorrhage (PPH), hemorrhagic shock, severe PPH, blood transfusion, hysterectomy, puerperal infection, preterm labor, NICU admission, and low birth weight. There was no difference in maternal and neonatal outcomes between marginal and partial PP, except for increased chances of preterm labor and low birth weight in partial PP. In the two-classification method, PP was the risk factor for most of the adverse maternal and neonatal outcomes, compared with low-lying placenta. Complete PP and low-lying placenta were associated with the highest and lowest risks of adverse pregnancy outcomes, respectively, whereas clinically similar outcomes were observed between marginal and partial PP. The three-classification of PP may be practical from the clinical perspective.

Ovarian cancer (OC) is the most frequent cause of death among patients with gynecologic malignancies. In recent years, the development of cisplatin (DDP) resistance has become an important reason for the poor prognosis of OC patients. Therefore, it is vital to explore the mechanism of DDP resistance in OC. In this study, microRNA-1246 (miR-1246) expression in OC and DDP-resistant OC cells was determined by RT-qPCR, and chemosensitivity to DDP was assessed by the CCK-8 assay. A dual-luciferase reporter assay was performed to confirm the interaction between miR-1246 and zinc finger 23 (ZNF23), while changes in ZNF23 expression were monitored by RT-qPCR, immunofluorescence, and western blot assays. Moreover, cell proliferation, cycle phase, and apoptosis were determined by EdU staining, flow cytometry, TUNEL staining, and Hoechst staining. Our data showed that miR-1246 was highly expressed in DDP-resistant OVCAR-3 and TOV-112D cells. Functionally, overexpression of miR-1246 markedly enhanced DDP resistance and cell proliferation, and suppressed cell cycle arrest and apoptosis of OC cells. Inhibition of miR-1246 expression significantly attenuated DDP resistance and cell proliferation, and increased cell cycle arrest and apoptosis in DDP-resistant OC cells. Furthermore, ZNF23 was identified as a target gene of miR-1246, and ZNF23 protein expression was notably downregulated in DDP-resistant OC cells. Moreover, overexpression of miR-1246 significantly downregulated the ZNF23 levels in OVCAR-3 and TOV-112D cells, and inhibition of miR-1246 upregulated the ZNF23 levels in the DDP-resistant OVCAR-3 and TOV-112D cells. In conclusion, miR-1246 might be a novel regulator of DDP-resistant OC that functions by regulating ZNF23 expression in DDP-resistant cells, as well as cell proliferation, cell cycle progression, and apoptosis.

Excessive scar formation post burn injury can cause great pain to the patients. MiR-133a-3p has been demonstrated to be anti-fibrotic in some fibrosis-related diseases. However, its possible role in scar formation has not been elucidated yet. In present study, the effect of miR-133a-3p on scar formation was investigated in a scalded model of mice. Moreover, the function of miR-133a-3p on proliferation and migration of scar-derived fibroblasts (SFs) was studied in vitro. It was found that miR-133a-3p was dramatically downregulated in scar tissue of scalded mice. Upregulation of miR-133a-3p by miR-133a-3p agomir obviously inhibited the scar formation in scalded mice. Histological staining showed that upregulation of miR-133a-3p attenuated the excessive deposition of collagen in scar tissue of scalded mice. In vitro study showed that upregulation of miR-133a-3p effectively suppressed the proliferation and migration of SFs. Besides, upregulation of miR-133a-3p attenuated the protein levels of α-smooth muscle actin (α-SMA) and collagen I, indicating that miR-133a-3p could suppress the activation of SFs. The expression of connective tissue growth factor (CTGF), a critical mediator in cell proliferation, migration and extracellular matrix (ECM) synthesis, was also downregulated by the upregulation of miR-133a-3p. Luciferase reporter assay validated that CTGF was directly targeted by miR-133a-3p. In addition, overexpression of CTGF abolished the effect of miR-133a-3p on inhibiting the proliferation, migration and activation of SFs, indicating that miR-133a-3p functioned by targeting CTGF. Therefore, miR-133a-3p might be a promising target for treating pathological scars.

Abdominal aortic aneurysm (AAA) is affected by multiple factors, including vessel wall cells, extracellular matrix, genetic disorders, etc.; however, the pathophysiology of AAA remains unclear. We recently found that thymidine phosphorylase (TYMP) is a signaling protein, and an increase of TYMP inhibits the proliferation of VSMCs, the major cell population that affects AAA progression. TYMP enhances platelet activity, thrombosis, and inflammation. These data suggest that TYMP may play a role in AAA formation. By using human AAA samples, we found that TYMP expression was significantly increased in AAA vessel walls than in healthy aortas. We thus further examined the role of TYMP in AAA formation using a mouse model. WT C57BL/6J and Tymp -/- mice were fed a western diet (TD.88137), started at 4 weeks (wks) old for 8 wks, and then received implantation of Ang II mini pump, which delivers Ang II to mice at a dose of 1 μg/kg/min for 4 wks. By echography, we found that Ang II perfusion dramatically increased inner aorta diameter at the diastolic phase in WT, but not Tymp -/- mice. Mice were sacrificed 4 wks after Ang II perfusion. AAA was confirmed in 3 of the 12 WT mice, but no AAA was found in all 11 Tymp -/- mice used. The AAA was mainly formed at the suprarenal artery level. Histological examination confirmed the presence of freshly formed or fibrotic hematoma. By using TYMP overexpressing rat VSMC cell line, C2, and its control cells, PC, we found that TYMP increased MMP2 production, secretion, and activation, which was diminished by tipiracil, a selective TYMP inhibitor. Ang II did not affect extracellular MMP2 activity in both PC and C2. TYMP facilitated TNF-α induced MMP2 activation. TYMP induced constitutive AKT phosphorylation, which was further enhanced by TNF-α. TYMP increased expression of active TGFβ1. Consequently, TYMP significantly enhanced thrombospondin-1 type 1 repeat domain (TSR) stimulated TGFβ1 signaling activation and expression of CTGF, which is correlated with severe fibrotic disorders and AAA. In summary, our study, for the first time, demonstrated that TYMP, a pyrimidine salvage pathway enzyme, plays an important role in regulating vascular biology, especially, VSMC function. TYMP-mediated microenvironment changes enhance the development of AAA.

Fat deposition is a complex economic trait regulated by polygenic genetic basis and environmental factors. Therefore, integrating multi-omics data to uncover its internal regulatory mechanism has attracted extensive attention. Here, we performed genomics and transcriptomics analysis to detect candidates affecting subcutaneous fat (SCF) deposition in beef cattle. The association of 770K SNPs with the backfat thickness captured nine significant SNPs within or near 11 genes. Additionally, 13 overlapping genes regarding fat deposition were determined via the analysis of differentially expressed genes and weighted gene co-expression network analysis (WGCNA). We then calculated the correlations of these genes with BFT and constructed their interaction network. Finally, seven biomarkers including ACACA, SCD, FASN, ACOX1, ELOVL5, HACD2, and HSD17B12 were screened. Notably, ACACA, identified by the integration of genomics and transcriptomics, was more likely to exert profound effects on SCF deposition. These findings provided novel insights into the regulation mechanism underlying bovine fat accumulation.

In this paper, we investigate the singularity near the degenerate points of the steady axisymmetric flow with general vorticity of an inviscid incompressible fluid acted on by gravity and with a free surface. We called the points on the free boundary at which the gradient of the stream function vanishes as the degenerate points. The main results in this paper give the different classifications of the singularity near the degenerate points on the free surface. More precisely, we obtained that at the stagnation points, the possible profiles must be a Stokes corner, or a horizontal cusp, or a horizontal flatness. At the degenerate points on the symmetric axis except the origin, the wave profile must be a cusp. At the origin, the possible wave profiles must be a Garabedian pointed bubble, or a horizontal cusp, or a horizontal flatness., 44 pages,6 figures

A critical step in advancing the practical application of copper-based organic light-emitting diodes (OLEDs) is to bridge the large gap between device efficiency and operational stability at practical luminance. Described is a panel of air- and thermally stable two-coordinate Cu

Regulating intermediates through elaborate catalyst design to control the reaction direction is crucial for promoting the selectivity of electrocatalytic CO

The creation of efficient artificial systems that mimic natural photosynthesis represents a key current challenge. Here, we describe a high-performance recyclable photocatalytic core–shell nanofibre system that integrates a cobalt catalyst and a photosensitizer in close proximity for hydrogen production from water using visible light. The composition, microstructure and dimensions—and thereby the catalytic activity—of the nanofibres were controlled through living crystallization-driven self-assembly. In this seeded growth strategy, block copolymers with crystallizable core-forming blocks and functional coronal segments were coassembled into low-dispersity, one-dimensional architectures. Under optimized conditions, the nanofibres promote the photocatalytic production of hydrogen from water with an overall quantum yield for solar energy conversion to hydrogen gas of ~4.0% (with a turnover number of >7,000 over 5 h, a frequency of >1,400 h−1 and a H2 production rate of >0.327 μmol h−1 with 1.34 μg of catalytic polymer (that is, >244,300 μmol h−1 g−1 of catalytic polymer)). Artificial systems capable of photocatalytic hydrogen production are not typically based on precisely controlled scaffolds. Now, statistical seeded crystallization of block copolymers—bearing either a pendant cobalt catalyst or a photosensitizer—from solution has been shown to yield recyclable, colloidally stable nanofibres that can be tailored to promote photocatalytic hydrogen production from water.

The regulatory role of toll-like receptor 4 (TLR4) in the inactivate staphylococcus epidermidis (ISE)-induced cornea inflammation is not well investigated. Here, TLR4 silence could decrease inflammatory cytokines in corneal epithelial cells treated with ISE. The mouse corneal epithelial cells were exposed to ISE for 24 h, either alone or with the NF-κB inhibitor, TLR4 lentivirus to bilaterally (knock-down or and overexpression). The expression of TLR4 in mouse corneal epithelial cells was investigated using western blot and qRT-PCR assay. The inflammatory cytokine levels were evaluated by qRT-PCR and ELISA, respectively. The relative impact factors of TLR4-mediated NF-κB signaling detected using western blot assay. Results show the expression levels of TLR4 and some inflammatory cytokines were significantly increased in corneal epithelial cells treated with ISE. TLR4 Silence markedly decreased ISE-induced production of IL12, TNF-α, CCL5, and CCL9 in corneal epithelial cells. Furthermore, the nuclear translocation of NF-κB p65 and myeloid differentiation protein 88 (MyD88) in the cells treated with ISE were further reduced by silencing TLR4. Inhibition of TLR4-mediated NF-κB signaling by using BAY11-7082 also alleviated ISE-induced inflammation. In the rescue experiment, transfected the stable TLR4 silenced corneal epithelial cells with TLR4 overexpression lentivirus, we found that TLR4 overexpression can restore the down-regulation of TLR4 and inflammatory cytokines (IL12, TNF-α, CCL9) caused by TLR4 knocked down. Therefore, ISE-induced cornea inflammation was due to the activation of the TLR4/MyD88/NF-κB signaling pathway, and dramatically stimulated IL12, TNF-α, CCL9 secretion. TLR4 silence presented mitigates damage in corneal epithelial cells treated with ISE.

Defective decidual function contributes to the pathogenesis of preeclampsia. However, the precise mechanism of defective decidua during preeclampsia has not been characterized. During decidualization, endometrial stromal cells undergo phenotypic changes that are consistent with mesenchymal-epithelial transition (MET). cGMP-dependent kinase protein I (PKGI)/VASP signaling is important in cell motility proliferation, differentiation and cell adhesion. To investigate this aim, we analyzed PKGI levels, phosphorylated VASP protein levels, and eNOS and sGC protein expression levels during pregnancy complicated by preeclampsia, which indicated that PKGI/VASP signaling function is decreased by the condition. Moreover, we evaluated the differential expression of genes that regulate MET in the decidua resulting from preeclampsia and healthy pregnancies. We discovered that vimentin mRNA levels are decreased in the decidua of preeclampsia, which indicates that excessive MET occurs in the decidua of preeclampsia pregnancies. A fundamental developmental MET program occurred in response to signaling pathways. These results suggest the important role of decreased PKGI/VASP signaling during excessive MET in the pathogenesis of preeclampsia.

In this review, noncovalent functionalization of single-wall carbon nanotubes (SWCNTs) is briefly reviewed. The functional materials summarized here include metalloporphyrin derivatives, biomolecules and conjugated polymers. Notably, time-resolved spectroscopic techniques such as time-resolved fluorescence and transient absorption were employed to directly investigate the electron transfer and recombination processes between the functionalities and the SWCNTs. In addition, Raman spectroscopy is also useful to identify the interaction and the electron transfer direction between both the functionalities and the SWCNTs. An improved understanding of the mechanisms of these SWCNT-based nanohybrids in terms of their structural and photophysical properties can provide more insights into the design of new electronic materials.

In recent years, the sharing of cybersecurity threat intelligence (hereinafter referred to as threat intelligence) has received increasing attention from national network security management organizations and network security enterprises. Academia and industry have conducted research on threat intelligence analysis and sharing. This paper first introduces the value and significance of threat intelligence. Then it introduces the commonly used threat intelligence analysis model. Then it organizes and classifies the threat intelligence sharing norms and threat intelligence vendors. Then it starts from the main problems faced by threat intelligence sharing. A solution to build regional network security capabilities is presented; finally, the future research direction of threat intelligence sharing is explored.

Spectral band selection is an important operation in the field of hyperspectral remote sensing. However, most of the techniques cannot satisfy the needs of efficiency and accuracy at the same time. In this paper, we present a novel spectral band selection method, fruit fly optimization algorithm (FOA). As yet, FOA has not been used to solve the problem of band selection in hyperspectral image. Through the study of the algorithm, we know that the advantages of FOA are its simple structure and fewer parameters to be adjusted, but the algorithm itself also has some drawbacks. Thus, we first analyze the shortcomings of the traditional FOA, and the corresponding proofs are given by mathematical method. Then, we separate the whole optimization process into two sub-processes, each of which plays a different role. According to the change of the current iteration information and historical optimum value, a fluctuation model is designed in sub-pro1, and its validity is analyzed and validated theoretically and experimentally. In sub-pro2, a control factor is defined to guide the change rate of the step size. These two sub-processes have their own emphasis, and they cooperate with each other, taking into account the global and local optimization capabilities of the algorithm. The test results on 26 benchmark functions also prove that the proposed algorithm is superior to various state-of-art comparison algorithms. Finally, we introduce the proposed algorithm into the band selection of hyperspectral remote sensing, the gratifying results indicate that the proposed algorithm has great potential in hyperspectral remote sensing field.

In the previous significant works by Alt et al. (1982) [2] and Alt et al. (1985) [6] , the existence of the two-dimensional asymmetric incompressible jet flow and compressible subsonic jet flow were established. However, the uniqueness of the asymmetric jet flow has remained an unsolved open problem. In this paper, we will establish the uniqueness of asymmetric jet flow not only for incompressible case but also for compressible subsonic case. Furthermore, as a byproduct, some properties of the jet flow are obtained, such as the location estimate and asymptotic deflection angle estimate of the jet in far field. Finally, a comparison theorem will be introduced to compressible subsonic jet flow.

Understanding the factors affecting the intersystem-crossing (ISC) rate constant (kISC) of transition-metal complexes is crucial to material design with tailored photophysical properties. Most of t...

In this paper, we are concerned with a jet and a cavity issuing from a semi-infinite long nozzle around a given obstacle in the axially symmetric case, which is called the axially symmetric incompressible Rethy flow. The existence and uniqueness of the axially symmetric Rethy flow are obtained via a variational approach when the nozzle and the obstacle are y-graphs and a mass flux at the inlet of the nozzle is given. This is the first result on the existence of axially symmetric flow with two free boundaries, which can be either jet or cavity. In order to show the existence, we develop a new method to show the vanishing and non-vanishing of the free boundaries by employing carefully the variational structures and the decay rate of the asymptotic behaviours of the solutions at the downstream.

Hydrogen-rich organic molecules such as alcohols are widely used as hydrogen donors in transfer hydrogenation. Nevertheless, water as a more abundant and ecofriendly hydrogen source has hardly been used due to the high difficulty in splitting water molecules. Herein, we designed a photocatalytic water-donating transfer hydrogenation (PWDTH) technique, in which hydrogen was extracted from water under light illumination and then in situ added to different unsaturated bonds (C-C, C-O, N-O) for chemical synthesis. Platinum-loaded carbon nitride (Pt/CN) was used as the model catalyst for this cascade reaction, which is beyond its normal applications for water splitting. This approach was highly accessible to efficiency optimization, either by modifying CN for extended light absorption and enhanced charge transfer or by alloying Pt with another metal for better catalytic activities. Remarkably, a quantum efficiency of up to 21.8% was achieved for nitrobenzene hydrogenation under 380 nm irradiation, which is 3 times higher than that obtained in the single water-splitting reaction, indicating that the PWDTH can be more rewarding than hydrogen evolution for solar energy harvesting. Deep insights into the underlying mechanism were provided by detailed measurements and interpretations of femtosecond transient absorption spectra, action spectra (quantum efficiency as a function of excitation wavelength), and reaction kinetic profiles under varied conditions including the variation of light intensities, temperatures, and water isotopes. The mild reaction conditions, simple processing, and broad substituent group tolerance endow this approach with a high potential toward a general solar-to-chemical conversion technique.

Background We translated a multigene expression index to predict sensitivity to endocrine therapy for Stage II–III breast cancer (SET2,3) to hybridization-based expression assays of formalin-fixed paraffin-embedded (FFPE) tissue sections. Here we report the technical validity with FFPE samples, including preanalytical and analytical performance. Methods We calibrated SET2,3 from microarrays (Affymetrix U133A) of frozen samples to hybridization-based assays of FFPE tissue, using bead-based QuantiGene Plex (QGP) and slide-based NanoString (NS). The following preanalytical and analytical conditions were tested in controlled studies: replicates within and between frozen and fixed samples, age of paraffin blocks, homogenization of fixed sections versus extracted RNA, core biopsy versus surgically resected tumor, technical replicates, precision over 20 weeks, limiting dilution, linear range, and analytical sensitivity. Lin’s concordance correlation coefficient (CCC) was used to measure concordance between measurements. Results SET2,3 index was calibrated to use with QGP (CCC 0.94) and NS (CCC 0.93) technical platforms, and was validated in two cohorts of older fixed samples using QGP (CCC 0.72, 0.85) and NS (CCC 0.78, 0.78). QGP assay was concordant using direct homogenization of fixed sections versus purified RNA (CCC 0.97) and between core and surgical sample types (CCC 0.90), with 100% accuracy in technical replicates, 1–9% coefficient of variation over 20 weekly tests, linear range 3.0–11.5 (log2 counts), and analytical sensitivity ≥2.0 (log2 counts). Conclusions Measurement of the novel SET2,3 assay was technically valid from fixed tumor sections of biopsy or resection samples using simple, inexpensive, hybridization methods, without the need for RNA purification.

Arylnitrenium ions have gained attention for their high reactivity toward guanosine, which in some cases has been linked to carcinogenesis. Although many studies have examined covalent addition reactions between arylnitrenium ions and guanosine, there is still some uncertainty regarding the attack position of nitrenium ions on guanosine and its derivatives. In this paper, we employ nanosecond transient absorption and nanosecond time-resolved resonance Raman spectroscopy to investigate the reaction between the N,N-di(4-bromophenyl) nitrenium ion (2) and guanosine. Our time-resolved spectroscopic results and photochemical product analysis results show that the reaction of guanosine with 2 generates an N7 intermediate that subsequently undergoes rearrangement and deprotonation to produce a C8 adduct. Comparing these results to our previous study between the 2-fluorenylnitrenium ion and guanosine indicates that the structure and properties of arylnitrenium ions are able to influence the reaction pathways and intermediate structures.

A well-posedness analysis of steady state of inviscid compressible subsonic impinging flows with non-zero vorticity is developed. A nonlinear nonhomogeneous second-order partial differential equation for the solution of the flow stream function is derived in terms of the inlet flow specifying the horizontal velocity. We first construct a subsonic solution to the impinging flow problem with special horizontal velocity and specific effluent fluxes in the outlets. Moreover, we showed that such a subsonic impinging flow with the same asymptotic behavior in the upstream and downstreams is unique. Furthermore, the existence, uniqueness and regularity of the interface separating the two fluids with different outlets are obtained. This result extends the recent result on the compressible subsonic irrotational impinging flows in [5] . Finally, as a byproduct, we obtain the existence of subsonic-sonic impinging flows.

Background: The SET2,3 index combines an accurate measure of transcription related to both estrogen and progesterone receptors (SETER/PR index) with a baseline prognostic index (BPI) derived from c-T Stage, c-N status and molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA). SET2,3 index was translated from a microarray-based signature to a customized hybridization assay that yields highly reproducible results from routine pathology tissue blocks. Methods: The SET2,3 index was calculated from microarray data prepared from baseline biopsies of HR+/HER2- cancers prior to neoadjuvant taxane-anthracycline chemotherapy followed by adjuvant endocrine therapy in: 1) a test set of 307 samples from the MDACC cohort with 8 years median follow-up (Affymetrix U133A microarrays, Symmans et al JAMA 2011), and 2) an independent blinded validation set of 268 high-risk Mammaprint (MP) samples from the I-SPY2 clinical trial with 3.8 years median follow-up (Agilent 44K microarrays, Agendia). The cut-point for high versus low SET2,3 was defined in the MDACC cohort and then tested in the I-SPY2 cohort. Association between the SET2,3 index and distant relapse-free survival (DRFS) was evaluated in each cohort using multivariate Cox regression models. One model adjusted for residual cancer burden (RCB) after neoadjuvant chemotherapy and its interaction with the SET2,3 index, also including treatment arm (experimental vs. control) in the I-SPY 2 trial. Another model adjusted for other prognostic gene expression signatures (GES) for recurrence score (RS), MP, or endopredict (EP) in the MDACC cohort, and actual MP in the I-SPY2 trial. A third model tested the ability of prognostic GES to substitute for RNA4 subtype (part of BPI) or SETER/PR index as components of the SET2,3 index. Results: Predicted sensitivity to endocrine therapy (SET2,3) and response to neoadjuvant chemotherapy (RCB) were independently prognostic, with nonsignificant (NS) interaction term, in multivariate analyses of the MDACC study: SET2,3 HR 0.26 (p=0.016); RCB HR 2.04 (p Conclusions: SET2,3 index of endocrine transcriptional activity in a pre-treatment core biopsy added independent significant prognostic information to any baseline prognostic score and response to neoadjuvant chemotherapy. Approximately 40% of clinical or genomic (MP) high-risk HR+/HER2- cancers had high SET2,3 index, and their response to neoadjuvant chemotherapy (RCB class) was not prognostic. This suggests that SET2,3 index might be used to select appropriate candidates for endocrine-based neoadjuvant treatments in clinical trials. Citation Format: Lili Du, Christina Yau, Lamorna Brown-Swigart, Rebekah Gould, Gillian L Hirst, I-SPY2 Consortium, Marieke van der Noordaa, Isabelle Bedrosian, Rachel M Layman, Vicente Valero, Laura van't Veer, Laura Esserman, W. Fraser Symmans. Prognostic contribution of predicted sensitivity to endocrine therapy (SET) prior to neoadjuvant chemotherapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-11-04.

Structurally robust tetradentate gold(III)-emitters have potent material applications but are rare and unprecedented for those displaying thermally activated delayed fluorescence (TADF). Herein, a novel synthetic route leading to the preparation of highly emissive, charge-neutral tetradentate [C^C^N^C] gold(III) complexes with 5-5-6-membered chelate rings has been developed through microwave-assisted C-H bond activation. These complexes show high thermal stability and with emission origin (3 IL, 3 ILCT, and TADF) tuned by varying the substituents of the C^C^N^C ligand. With phenoxazine/diphenylamine substituent, we prepared the first tetradentate gold(III) complexes that are TADF emitters with emission quantum yields of up to 94 % and emission lifetimes of down to 0.62 μs in deoxygenated toluene. These tetradentate AuIII TADF emitters showed good performance in vacuum-deposited OLEDs with maximum EQEs of up to 25 % and LT95 of up to 5280 h at 100 cd m-2 .

The realization of photocatalysis for practical synthetic application hinges on the development of inexpensive photocatalysts which can be prepared on a large scale. Herein an air-stable, visible-light-absorbing photoluminescent tungsten(vi) complex which can be conveniently prepared at the gram-scale is described. This complex could catalyse photochemical organic transformation reactions including borylation of aryl halides, such as aryl chloride, reductive coupling of benzyl bromides for C-C bond formation, reductive coupling of phenacyl bromides, and decarboxylative coupling of redox-active esters of alkyl carboxylic acid with high product yields and broad functional group tolerance.

This research aims to characterize the differences in clinical features and prognostic factors between younger and older breast cancer (BC) patients in China.All patients who were recently diagnosed with BC between January 1, 2015 and December 31, 2016 at Shanxi Province Cancer Hospital were recruited. We collected the epidemiological and clinical data as well as the follow-up information.Out of the 1968 BC patients who met the criteria for analysis, 227 (11.53%) were under 40 years of age with a median age of 34 years at diagnosis. All patients were classified into the age 40, age 40-59, and age ≥ 60 groups. There were significant differences in the histology, tumor size, T stage, grade, and human epidermal growth factor receptor-2 (HER-2) levels among the three groups (all P 0.05). The 5-year overall survival (OS) rates were 86.34%, 89.58%, and 84.84% for the age 40, age 40-59, and age ≥ 60 groups, respectively. The TNM stage was the only predictor of clinical outcome in all BC patients. The prognostic value of intrinsic subtypes for OS was different among the three groups.Our study helped identify an age-related prognostic indicator of adverse events in BC patients and showed that young women with BC exhibited more aggressive clinical and pathological features. Our findings may facilitate clinical management and therapeutic interventions in young BC patients, especially in young women with a history of exposure to risk factors and age 40 years.

The impacts of the current COVID-19 pandemic on maternal and foetal health are enormous and of serious concern. However, the influence of SARS-CoV-2 infection at early-to-mid gestation on maternal and foetal health remains unclear.Here, we report the follow-up study of a pregnant woman of her whole infective course of SARS-CoV-2, from asymptomatic infection at gestational week 20 to mild and then severe illness state, and finally cured at Week 24. Following caesarean section due to incomplete uterine rupture at Week 28, histological examinations on the placenta and foetal tissues as well as single-cell RNA sequencing (scRNA-seq) for the placenta were performed.Compared with the gestational age-matched control placentas, the placenta from this COVID-19 case exhibited more syncytial knots and lowered expression of syncytiotrophoblast-related genes. The scRNA-seq analysis demonstrated impaired trophoblast differentiation, activation of antiviral and inflammatory CD8 T cells, as well as the tight association of increased inflammatory responses in the placenta with complement over-activation in macrophages. In addition, levels of several inflammatory factors increased in the placenta and foetal blood.These findings illustrate a systematic cellular and molecular signature of placental insufficiency and immune activation at the maternal-foetal interface that may be attributed to SARS-CoV-2 infection at the midgestation stage, which highly suggests the extensive care for maternal and foetal outcomes in pregnant women suffering from COVID-19.