Continuous Ultrathin Zwitterionic Covalent Organic Framework Membrane Via Surface-Initiated Polymerization Toward Superior Water Retention.

Efficient construction of proton transport channels in proton exchange membranes maintaining conductivity under varied humidity is critical for the development of fuel cells. Covalent organic frameworks (COFs) hold great potential in providing precise and fast ion transport channels. However, the preparation of continuous free-standing COF membranes retaining their inherent structural advantages to realize excellent proton conduction performance is a major challenge. Herein, a zwitterionic COF material bearing positive ammonium ions and negative sulphonic acid ions is developed. Free-standing COF membrane with adjustable thickness is constructed via surface-initiated polymerization of COF monomers. The porosity, continuity, and stability of the membranes are demonstrated via the transmission electron microscopy (TEM), atomic force microscopy (AFM), and scanning electron microscopy (SEM) characterization. The rigidity of the COF structure avoids swelling in aqueous solution, which improves the chemical stability of the proton exchange membranes and improves the performance stability. In the higher humidity range (50-90%), the prepared zwitterionic COF membrane exhibits superior capability in retaining the conductivity compared to COF membrane merely bearing sulphonic acid group. The established strategy shows the potential for the application of zwitterionic COF in the proton exchange membrane fuel cells.

AFM-Based Poroelastic@Membrane Analysis of Cells and its Opportunities for Translational Medicine.

Cell mechanics is an emerging field of research for translational medicine. Here, the cell is modeled as poroelastic cytoplasm wrapped by tensile membrane (poroelastic@membrane model) and is characterized by the atomic force microscopy (AFM). The parameters of cytoskeleton network modulus EC , cytoplasmic apparent viscosity ηC , and cytoplasmic diffusion coefficient DC are used to describe the mechanical behavior of cytoplasm, and membrane tension γ is used to evaluate the cell membrane. Poroelastic@membrane analysis of breast cells and urothelial cells show that non-cancer cells and cancer cells have different distribution regions and distribution trends in the four-dimensional space composed of EC , ηC . From non-cancer to cancer cells, there is often a trend of γ, EC , ηC decreases and DC increases. Patients with urothelial carcinoma at different malignant stages can be distinguished at high sensitivity and specificity by analyzing the urothelial cells from tissue or urine. However, sampling directly from tumor tissues is an invasive method, may lead to undesirable consequences. Thus, AFM-based poroelastic@membrane analysis of urothelial cells from urine may provide a non-invasive and no-bio-label method to detecting urothelial carcinoma.

Diabetes, Obesity, and Pathological Upstaging in Renal Cell Carcinoma: Results From a Large Multi-institutional Consortium.

PURPOSE: We sought to determine whether clinical risk factors and morphometric features on preoperative imaging can be utilized to identify those patients with cT1 tumors who are at higher risk of upstaging (pT3a). MATERIALS AND METHODS: We performed a retrospective international case-control study of consecutive patients treated surgically with radical or partial nephrectomy for nonmetastatic renal cell carcinoma (cT1 N0) conducted between January 2010 and December 2018. Multivariable logistic regression models were used to study associations of preoperative risk factors on pT3a pathological upstaging among all patients, as well as subsets with those with preoperative tumors ≤4 cm, renal nephrometry scores, tumors ≤4 cm with nephrometry scores, and clear cell histology. We also examined association with pT3a subsets (renal vein, sinus fat, perinephric fat). RESULTS: Among the 4,092 partial nephrectomy and 2,056 radical nephrectomy patients, pathological upstaging occurred in 4.9% and 23.3%, respectively. Among each group independent factors associated with pT3a upstaging were increasing preoperative tumor size, increasing age, and the presence of diabetes. Specifically, among partial nephrectomy subjects diabetes (OR=1.65; 95% CI 1.17, 2.29), male sex (OR=1.62; 95% CI 1.14, 2.33), and increasing BMI (OR=1.03; 95% CI 1.00, 1.05 per 1 unit BMI) were statistically associated with upstaging. Subset analyses identified hilar tumors as more likely to be upstaged (partial nephrectomy OR=1.91; 95% CI 1.12, 3.16; radical nephrectomy OR=2.16; 95% CI 1.44, 3.25). CONCLUSIONS: Diabetes and higher BMI were associated with pathological upstaging, as were preoperative tumor size, increased age, and male sex. Similarly, hilar tumors were frequently upstaged.

Dynamic stability of a blue multi-resonance thermally activated delayed fluorescence molecule without damaging the luminescence properties.

The instability of blue emitters is one of the shortcomings of organic light-emitting diodes (OLEDs) in industrial applications. This instability is intrinsically associated with the basic transitions and reactions in the excited states. In this work, using the framework of Fermi's golden rule and DFT/TDDFT, the mechanisms of the transitions and reactions of a typical boron based multi-resonance thermally activated delayed fluorescence emitter involving the excited states were investigated. A dynamic stability mechanism describing recycling between the dissociation of the molecular structure in the T1 state and restoration in the S0 state dominated by steric effects was discovered. Applying knowledge of this mechanism, a small modification was made to the molecular structure, and the stability was increased without degrading other luminescence properties such as the luminescence color, FWHM, reverse intersystem crossing, fluorescence quantum yield, and internal quantum yield.

Crystalline matrix-activated spin-forbidden transitions of engineered organic crystals.

Spin-forbidden excitation is an efficient way to obtain triplet excitons directly from the ground state of organic semiconductors. According to perturbation theory under the framework of Fermi's golden rule, this process requires spin-orbit coupling (SOC) and the transition dipole moment (TDM) to be combined through an intermediate state that mixes the initial and final states. While previous research has focused mostly on enhancing SOC, little attention has been paid to engineering the coupling between SOC and the TDM in organic materials. In this study, a series of engineered crystals were designed by doping guest molecules into host organic crystals. The confinement of the guest molecule within a crystalline matrix of the host provides a strong intermolecular interaction to couple both SOC and the TDM. This in turn activates the spin-forbidden excitation directly from the ground state to a "dark" triplet state. Based on a comparison of different engineered crystals, strong intermolecular interaction is identified to induce a distortion of the ligands and further enhancing the spin-forbidden excitation. This work outlines a strategy for designing spin-forbidden excitation.

Correction: Crystalline matrix-activated spin-forbidden transitions of engineered organic crystals.

Correction for 'Crystalline matrix-activated spin-forbidden transitions of engineered organic crystals' by Heming Zhang et al., Phys. Chem. Chem. Phys., 2023, 25, 11102-11110, DOI: https://doi.org/10.1039/d3cp00187c.

Comparative analysis of surgical and oncologic outcomes of robotic, laparoscopic and open radical nephrectomy with venous thrombectomy: a propensity-matched cohort study.

OBJECTIVE: To provide insight into the surgical and oncological outcomes of robotic, laparoscopic and open radical nephrectomy with venous thrombectomy (RALRN-VT, LRN-VT, ORN-VT) in patients with renal tumor and venous thrombus. MATERIALS AND METHODS: A propensity-matched retrospective cohort study containing 324 patients with renal tumor and venous thrombus from January 2014 to August 2021 was analyzed. We compared surgical outcomes and we used the Kalan-Meier method to assess the overall survival (OS), tumor-specific survival (TSS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). The Pearson chi-square test and Fisher exact test, Wilcoxon rank sum test, Cox proportional hazards regression model and log-rank test were used. RESULTS: After matching, baseline characteristics were comparable in the RALRN-VT, LRN-VT and ORN-VT group. The RALRN-VT group had the least operative time (median 134 min vs 289 min vs 330 min, P < 0.001), the least blood loss (median 250 ml vs 500 ml vs 1000 ml, P < 0.001) and the fewest packed red blood cells transfusion (median 400 ml vs 800 ml vs 1200 ml, P < 0.001). The ORN-VT group had the highest complication rate (18.2 vs 22.7 vs 43.2%, P = 0.005), the highest Clavien grade (P = 0.001) and the longest postoperative hospital stay (median 7d vs 8d vs 10d, P < 0.001). No significant difference in OS, TSS and MFS between the minimally invasive procedures (MIP, including RALRN-VT and LRN-VT) group and ORN-VT group was found. The hazard ratio of LRFS for the MIP group was 0.20 (95% CI 0.06-0.70, P = 0.01) compared with ORN-VT group. CONCLUSIONS: RALRN-VT can result in the best surgical outcomes compared with LRN-VT and ORN-VT. The MIP group had a better LRFS compared with ORN-VT group.

Long-term outcomes after cytoreductive nephrectomy and thrombectomy of patients with metastatic renal cell carcinoma with venous tumor thrombus: a retrospective study from a large Chinese center.

BACKGROUND: Targeted therapy combined with immunotherapy is the current first-line treatment for metastatic renal cell carcinoma (mRCC), but patients with tumor thrombus (TT) may suffer from lower limb edema or even sudden cardiac death, so the purpose of this study is to investigate the efficacy and safety of surgical treatment in patients with mRCC and TT and explore worse factors to affect the prognosis in this series of patients. PATIENTS AND METHODS: A total of 85 mRCC patients with TT who received cytoreductive nephrectomy and thrombectomy at our medical center from 2014 to 2023 are included. All patients received postoperative systemic therapy. Overall survival (OS) is defined as the time from surgery to death due to any reason or the last follow-up. Kaplan-Meier analysis was performed to evaluate OS and differences among groups were tested by log-rank. Multivariable Cox proportional hazards analysis was performed to ascertain independent relationships between clinicopathological factors and OS. RESULTS: The median age of patients was 58 years old. Eleven patients (12.9%) had no symptoms, 39 patients (45.9%) had local symptoms, 15 patients (17.6%) had systemic symptoms, and 20 patients (23.5%) had both. Mayo grade of TT was 0, 1, 2, 3, and 4 for 12, 27, 31, 7, and 8 patients respectively. Fifty-five patients had lung metastasis, 23 had bone metastasis, 16 had liver metastasis, 13 had adrenal metastasis, and 9 had lymph node metastasis. Of all patients, 17 patients had multiple metastases. The median operation time is 289 min and the median intraoperative hemorrhage is 800 ml. Twenty-eight patients experienced postoperative complications, 8 of which were serious complications of modified Clavien grade III or higher. The median OS of all patients was 33 months and median follow up time was 26 months. In multivariate analysis, systemic symptom (p = 0.00753), pathological type (p = 0.0166), sarcomatous degeneration (p = 0.0334), and perirenal fat infiltration (p = 0.0202) are independent predictors of OS. CONCLUSION: Cytoreductive nephrectomy and thrombectomy is relatively safe and effective for patients with mRCC accompanied by TT. In this series of patients, the worse prognosis is associated with systemic symptoms, non-clear cell carcinoma, sarcomatous degeneration and perirenal fat infiltration.

Genetic-algorithm-aided ultra-broadband perfect absorbers using plasmonic metamaterials.

Complete absorption of electromagnetic waves is paramount in today's applications, ranging from photovoltaics to cross-talk prevention into sensitive devices. In this context, we use a genetic algorithm (GA) strategy to optimize absorption properties of periodic arrays of truncated square-based pyramids made of alternating stacks of metal/dielectric layers. We target ultra-broadband quasi-perfect absorption of normally incident electromagnetic radiations in the visible and near-infrared ranges (wavelength comprised between 420 and 1600 nm). We compare the results one can obtain by considering one, two or three stacks of either Ni, Ti, Al, Cr, Ag, Cu, Au or W for the metal, and poly(methyl methacrylate) (PMMA) for the dielectric. More than 1017 configurations of geometrical parameters are explored and reduced to a few optimal ones. This extensive study shows that Ni/PMMA, Ti/PMMA, Cr/PMMA and W/PMMA provide high-quality solutions with an integrated absorptance higher than 99% over the considered wavelength range, when considering realistic implementation of these ultra-broadband perfect electromagnetic absorbers. Robustness of optimal solutions with respect to geometrical parameters is investigated and local absorption maps are provided. Moreover, we confirm that these optimal solutions maintain quasi-perfect broadband absorption properties over a broad angular range when changing the inclination of the incident radiation. The study also reveals that noble metals (Au, Ag, Cu) do not provide the highest performance for the present application.

Deep-Red and Near-Infrared Iridium Complexes with Fine-Tuned Emission Colors by Adjusting Trifluoromethyl Substitution on Cyclometalated Ligands Combined with Matched Ancillary Ligands for Highly Efficient Phosphorescent Organic Light-Emitting Diodes.

Six novel Ir(C^N)2(L^X)-type heteroleptic iridium complexes with deep-red and near-infrared region (NIR)-emitting coverage were constructed through the cross matching of various cyclometalating (C^N) and ancillary (LX) ligands. Here, three novel C^N ligands were designed by introducing the electron-withdrawing group CF3 on the ortho (o-), meta (m-), and para (p-) positions of the phenyl ring in the 1-phenylisoquinoline (piq) group, which were combined with two electron-rich LX ligands (dipba and dipg), respectively, leading to subsequent iridium complexes with gradually changing emission colors from deep red (≈660 nm) to NIR (≈700 nm). Moreover, a series of phosphorescent organic light-emitting diodes (PhOLEDs) were fabricated by employing these phosphors as dopant emitters with two doping concentrations, 5% and 10%, respectively. They exhibited efficient electroluminescence (EL) with significantly high EQE values: >15.0% for deep red light0 (λmax = 664 nm) and >4.0% for NIR cases (λmax = 704 nm) at a high luminance level of 100 cd m-2. This work not only provides a promising approach for finely tuning the emission color of red phosphors via the easily accessible molecular design strategy, but also enables the establishment of an effective method for enriching phosphorescent-emitting molecules for practical applications, especially in the deep-red and near-infrared region (NIR).

Single Molecules in Strong Optical Fields: A Variable-Temperature Molecular Junction Spectroscopy Setup.

In order to advance the development of molecular electronic devices, it is mandatory to improve the understanding of electron transport and functionalities in single molecules, integrated in a well-defined environment. However, limited information can be obtained by solely analyzing I-V characteristics, whence multiparameter studies are required to obtain more information on such systems including chemical bonds, geometry, and intramolecular strain. Therefore, we developed an analytical method incorporating an optical near-field technique, which allows us to investigate single-molecule junctions at variable temperatures in strong optical fields. An apertureless near-field emitter acts as a counter electrode and a plasmonic waveguide to focus surface plasmon polaritons into the molecular junctions, where a strongly enhanced evanescent field is confined to only a few nanometers around the apex of the tip. The proof of concept, even at low temperatures, is demonstrated by simultaneously investigating electronic and optical features of the molecule p-terphenyl-4,4″-dithiol in dependence of its charge state. This multichannel method can be employed to analyze a variety of nearly unexplored properties in single-molecule junctions such as photoconductance and photocurrent generation and allows a characterization of the molecular junctions by spectroscopic means as well.

Inhibitory Effect of CCK-8 on Methamphetamine-Induced Apoptosis.

OBJECTIVES: To investigate the inhibitory effect of cholecystokinin octapeptide (CCK-8) binding to cholecystokinin 2 receptor (CCK2R) on methamphetamine (METH)-induced neuronal apoptosis, and to explore the signal transduction mechanism of ß-arrestin 2 in CCK-8 inhibiting METH-induced neuronal apoptosis. METHODS: SH-SY5Y cell line was cultured, and HEK293-CCK1R and HEK293-CCK2R cell line were constructed by lentivirus transfection. Small interfering RNA (siRNA) was used to knockdown the expression of ß-arrestin 2. Annexin Ⅴ-FITC/PI staining and flow cytometry were used to detect the apoptotic rate of cells, and Western blotting was used to detect the expression of apoptosis-related proteins. RESULTS: The apoptosis of SH-SY5Y cells was induced by 1 mmol/L and 2 mmol/L METH treatment, the number of nuclear fragmentation and pyknotic cells was significantly increased, and the expression of apoptosis-related proteins Bax and cleaved caspase-3 were increased. CCK-8 pre-treatment at the dose of 0.1 mmol/L and 1 mmol/L significantly reversed METH-induced apoptosis in SH-SY5Y cells, and inhibited cell nuclear fragmentation, pyknosis and the changes of apoptosis-related proteins induced by METH. In lentivirus transfected HEK293-CCK1R and HEK293-CCK2R cells, the results revealed that CCK-8 had no significant effect on METH-induced changes of apoptosis-related proteins in HEK293-CCK1R cells, but it could inhibit the expression level of apoptosis-related proteins in HEK293-CCK2R cells induced by METH. The inhibitory effect of CCK-8 on METH-induced apoptosis was blocked by the knockdown of ß-arrestin 2 expression in SH-SY5Y cells. CONCLUSIONS: CCK-8 can bind to CCK2R and exert an inhibitory effect on METH-induced apoptosis by activating the ß-arrestin 2 signal.

Electron-Phonon Coupling in Current-Driven Single-Molecule Junctions.

Vibrational excitations provoked by coupling effects during charge transport through single molecules are intrinsic energy dissipation phenomena, in close analogy to electron-phonon coupling in solids. One fundamental challenge in molecular electronics is the quantitative determination of charge-vibrational (electron-phonon) coupling for single-molecule junctions. The ability to record electron-phonon coupling phenomena at the single-molecule level is a key prerequisite to fully rationalize and optimize charge-transport efficiencies for specific molecular configurations and currents. Here we exemplarily determine the pertaining coupling characteristics for a current-carrying chemically well-defined molecule by synchronous vibrational and current-voltage spectroscopy. These metal-molecule-metal junction insights are complemented by time-resolved infrared spectroscopy to assess the intramolecular vibrational relaxation dynamics. By measuring and analyzing the steady-state vibrational distribution during transient charge transport in a bis-phenylethynyl-anthracene derivative using anti-Stokes Raman scattering, we find ∼0.5 vibrational excitations per elementary charge passing through the metal-molecule-metal junction, by means of a rate model ansatz and quantum-chemical calculations.

The key points in the pre-analytical procedures of blood and urine samples in metabolomics studies.

BACKGROUND: Metabolomics provides measurement of numerous metabolites in human samples, which can be a useful tool in clinical research. Blood and urine are regarded as preferred subjects of study because of their minimally invasive collection and simple preprocessing methods. Adhering to standard operating procedures is an essential factor in ensuring excellent sample quality and reliable results. AIM OF REVIEW: In this review, we summarize the studies about the impacts of various preprocessing factors on metabolomics studies involving clinical blood and urine samples in order to provide guidance for sample collection and preprocessing. KEY SCIENTIFIC CONCEPTS OF REVIEW: Clinical information is important for sample grouping and data analysis which deserves attention before sample collection. Plasma and serum as well as urine samples are appropriate for metabolomics analysis. Collection tubes, hemolysis, delay at room temperature, and freeze-thaw cycles may affect metabolic profiles of blood samples. Collection time, time between sampling and examination, contamination, normalization strategies, and storage conditions may alter analysis results of urine samples. Taking these collection and preprocessing factors into account, this review provides suggestions of standard sample preprocessing.

Impact of Body Mass Index and Pretreatment Hemoglobin Level on Prognosis Following Radical Cystectomy for Bladder Cancer in Males and Females.

OBJECTIVE: To assess the impact of pretreatment hemoglobin (Hb) and body mass index (BMI) on overall survival (OS) following radical cystectomy (RC) for bladder cancer (BCa) in males versus females. MATERIALS AND METHODS: We retrospectively reviewed 152 patients treated with RC for BCa between 2012 and 2016. Hb was categorized as low Hb or high Hb. BMI was classified as underweight, overweight, or obese. Univariate and multivariate Cox regression models were used to evaluate the association of Hb and BMI with OS both in the entire cohort and in gender subgroups. RESULTS: In these 152 BCa cases, 79 cases (52.0%) were categorized as low Hb, and 67 cases (44.1%) were overweight or obese. Both Hb (p = 0.001) and BMI (p = 0.046) were independent prognostic factors for the entire cohort. In females, only Hb (p = 0.012) and BMI (p = 0.027) were significant prognostic factors. In males, Hb (p = 0.024) was an independent prognostic factor, but BMI (p = 0.142) lost significance in multivariate analysis. CONCLUSION: Our results found that both higher pretreatment Hb and higher BMI were associated with favorable prognosis for OS in BCa treated with RC. The differing impact of Hb and BMI on prognosis in progression of BCa in males versus females suggests there is involvement of sex hormone pathways.

Nontargeted metabolomic analysis of skeletal muscle in a dehydroepiandrosterone-induced mouse model of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy and an important metabolic disorder in women of reproductive age. Insulin resistance (IR) is one of its most important clinical features in patients with PCOS. Androgen excess-induced mitochondrial dysfunction contributes to skeletal muscle IR in dehydroepiandrosterone (DHEA)-induced PCOS mice. The effect of androgen excess on the skeletal muscle, however, is incompletely characterized. A nontargeted metabolomics approach was thus applied to analyze the metabolites in skeletal muscle of DHEA-induced PCOS mice. Data from metabolomic analysis revealed the significant changes in 32 metabolites and the marked impact of five metabolic pathways. ATP production was also found to be significantly reduced in skeletal muscle of DHEA mice. Combined with the quantification of type I and II myofibers and lipid measurement in the skeletal muscle of the mice, the results from the present study supported the role of mitochondrial impairment rather than lipid accumulation in the pathogenesis of skeletal muscle IR in DHEA-induced PCOS mice. In summary, we show here for the first time the profile of the metabolites in the skeletal muscle of DHEA-induced PCOS mice which exhibit IR. The work would help better understand the pathology of skeletal muscle IR in PCOS.

Effects of fat-to-sugar ratio in excess dietary energy on lipid abnormalities: a 7-month prospective feeding study in adult cynomolgus monkeys.

BACKGROUND: Excess energy intake contributes to metabolic disorders. However, the relationship between excess sugar and fat in their contributions to metabolic abnormalities remains to be further elucidated. Here we conducted a prospective feeding experiment to evaluate effects of dietary fat-to-sugar ratio on diet-induced metabolic abnormalities in adult cynomolgus monkeys. METHODS: Four groups of adult cynomolgus monkeys were fed regular chow plus emulsion with combinations of high sugar (HS) or low sugar (HS) and low fat (LF) or high fat (HF) for 7 months. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and blood glucose were measured for all the four groups of animals during the experiment. RESULTS: Plasma levels of TC and LDL-C gradually increased in all 4 diets groups, with the highest increase found in the LSHF group compared to the other three groups (P = 0.0018 and P = 0.0005 respectively). HF induced increased fasting glucose (P = 0.0077) and HS induced higher TG (P = 0.0227) respectively. Intriguingly, HSHF led to dramatically smaller magnitude of increase in LDL-C and TC levels compared to LSHF, while such difference was absent between the LSLF and LSHF groups. Our findings thus indicate interactive effects of HS and HF on TC and LDL-C. In addition, HF exhibited stronger effects on lipid abnormalities than HS. CONCLUSIONS: In the current study, our prospective feeding experiment in adult cynomolgus monkeys revealed effects of different fat-to-sugar ratios on diet-induced metabolic abnormalities. Furthermore, our findings suggest that not only excess dietary energy but also the balance of dietary fat-to-sugar ratio matters in diet-induced lipid abnormalities.

Identification and Characterization of a Luteinizing Hormone Receptor (LHR) Homolog from the Chinese Mitten Crab Eriocheir sinensis.

Luteinizing hormone (LH), a pituitary gonadotropin, coupled with LH receptor (LHR) is essential for the regulation of the gonadal maturation in vertebrates. Although LH homolog has been detected by immunocytochemical analysis, and its possible role in ovarian maturation was revealed in decapod crustacean, so far there is no molecular evidence for the existence of LHR. In this study, we cloned a novel LHR homolog (named EsLHR) from the Chinese mitten crab Eriocheir sinensis. The complete sequence of the EsLHR cDNA was 2775bp, encoding a protein of 924 amino acids, sharing 71% amino acids identity with the ant Zootermopsis nevadensis LHR. EsLHR expression was found to be high in the ovary, while low in testis, gill, brain, and heart, and no expression in the thoracic ganglion, eye stalk, muscle, and hepatopancreas. Quantitative PCR revealed that the expression level of EsLHR mRNA was significantly higher in the ovaries in previtellogenic (Pvt), late vitellogenic (Lvt), and germinal vesicle breakdown (GVBD) stages than that in the vitellogenic (Mvt) and early vitellogenic (Evt) stages (P < 0.05), and, the highest and the lowest expression were in Lvt, and Evt, respectively. The strong signal was mainly localized in the ooplasm of Pvt oocyte as detected by in situ hybridization. The crab GnRH homolog can significantly induce the expression of EsLHR mRNA at 36 hours post injection in vivo (P < 0.01), suggesting that EsLHR may be involved in regulating ovarian development through GnRH signaling pathway in the mitten crab.

Voltage-Driven Conformational Switching with Distinct Raman Signature in a Single-Molecule Junction.

Precisely controlling well-defined, stable single-molecule junctions represents a pillar of single-molecule electronics. Early attempts to establish computing with molecular switching arrays were partly challenged by limitations in the direct chemical characterization of metal-molecule-metal junctions. While cryogenic scanning probe studies have advanced the mechanistic understanding of current- and voltage-induced conformational switching, metal-molecule-metal conformations are still largely inferred from indirect evidence. Hence, the development of robust, chemically sensitive techniques is instrumental for advancement in the field. Here we probe the conformation of a two-state molecular switch with vibrational spectroscopy, while simultaneously operating it by means of the applied voltage. Our study emphasizes measurements of single-molecule Raman spectra in a room-temperature stable single-molecule switch presenting a signal modulation of nearly 2 orders of magnitude.

Administration of ubiquitin-activating enzyme UBA1 inhibitor PYR-41 attenuates angiotensin II-induced cardiac remodeling in mice.

Pathological cardiac hypertrophy is the main risk factor for heart diseases. The ubiquitin-proteasome system (UPS) is the major intracellular protein degradation system involved in the development of cardiac hypertrophic remodeling. Ubiquitin-activating enzyme E1, a key component of the UPS, catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation via proteasome. However, the functional role of E1 (UBA1) in regulation of hypertrophic remodeling in angiotensin II (Ang II)-infused mice remains unknown. In this study, male wild-type mice were treated with UBA1 inhibitor PYR-41 at two doses of 5 and 10 mg and infused with Ang II (1000 ng/kg/min) for 14 days. Systolic blood pressure was detected by using tail-cuff system. Cardiac function was assessed by echocardiography. Hypertrophic remodeling was analyzed examined by histological examinations. The expressions of genes and proteins were detected by quantitative real-time PCR and immunoblotting analysis. After 14 days, Ang II infusion significantly increased UBA1 expression at both mRNA and protein levels in the hearts. Furthermore, Ang II-infused mice showed a significant increase in systolic blood pressure compensatory cardiac function, hypertrophy, interstitial fibrosis, inflammation and oxidative stress compared with saline-treated controls, whereas these effects were dose-dependently attenuated in PYR-41-treated mice. These beneficial actions were associated mainly with inhibition of PTEN degradation and multiple downstream mediators (AKT, ERK1/2, STAT3, TGF-ß/Smad2/3 and NF-kB(p65)). In conclusion, these results indicate that inhibition of UBA1 suppresses Ang II-induced hypertrophic remodeling, and suggest that administration of low dose PYR-41 may be a new potential therapeutic approach for treating hypertensive heart diseases.