p53 exerts anticancer effects by regulating enhancer formation and activity

The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat cancer.Recent studies have shown extensive p53 binding to enhancer elements.However,whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood.In the current study,we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout(KO)human bronchial epithelial cells(BEAS-2B).A total of 943 active regular enhancers and 370 super-enhancers(SEs)disappeared upon the deletion of p53,indicating that p53 modulates the activity of hundreds of enhancer elements.We found that one p53-dependent SE,located on chromosome 9 and designated as KLF4-SE,regulated the expression of the Krüppel-like factor 4(KLF4)gene.Furthermore,the deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression,but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model.Subsequently,in TP53 KO cells,the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency.Consistently,KLF4 expression also decreased in lung cancer tissues and cell lines.It appeared that overexpression of KLF4 significantly suppressed the proliferation and migration of lung cancer cells.Collectively,our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function.Therefore,our findings offer some novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.

Coexistent alcohol-related cirrhosis and chronic pancreatitis have a comparable phenotype to either disease alone:A comparative retrospective analysis

BACKGROUND Alcohol use disorder is a prevalent disease in the United States.It is a well-demonstrated cause of recurrent and long-standing liver and pancreatic injury which can lead to alcohol-related liver cirrhosis(ALC)and chronic pancreatitis(ACP).ALC and ACP are associated with significant healthcare utilization,cost burden,and mortality.The prevalence of coexistent disease(CD)ranges widely in the literature and the intersection between ALC and ACP is inconsistently charac-terized.As such,the clinical profile of coexistent ALC and ACP remains poorly understood.We hypothesized that patients with CD have a worse phenotype when compared to single organ disease.AIM To compare the clinical profile and outcomes of patients with CD from those with ALC or ACP Only.METHODS In this retrospective comparative analysis,we reviewed international classi-fication of disease 9/10 codes and electronic health records of adult patients with verified ALC Only(n=135),ACP Only(n=87),and CD(n=133)who received care at UPMC Presbyterian-Shadyside Hospital.ALC was defined by histology,imaging or clinical evidence of cirrhosis or hepatic decompensation.ACP was defined by imaging findings of pancreatic calcifications,moderate-severe pancreatic duct dilatation,irregularity or atrophy.We compared demographics,pertinent clinical variables,healthcare utilization,and mortality for patients with CD with those who had single organ disease.RESULTS Compared to CD or ACP Only,patients with ALC Only were more likely to be older,Caucasian,have higher body mass index,and Hepatitis B or C infection.CD patients(vs ALC Only)were less likely to have imaging evidence of cirrhosis and portal hypertension despite possessing similar MELD-Na and Child C scores at the most recent contact.CD patients(vs ACP Only)were less likely to have acute or recurrent acute pancreatitis,diabetes mellitus,insulin use,oral pancreatic enzyme therapy,and need for endoscopic therapy or pancreatic surgery.The number of hospitalizations in patients with CD were similar to ACP Only but significantly higher than ALC Only.The overall mortality in patients with CD was similar to ALC Only but trended to be higher than ACP Only(P=0.10).CONCLUSION CD does not have a worse phenotype compared with single organ disease.The dominant phenotype in CD is similar to ALC Only which should be the focus in longitudinal follow-up.

Demonstration of the Source of Motor Program Signal: Study on the Correlation between Muscle Strength and sEMG Signal in Normal Children and Adults

To investigate the relationship between muscle strength and sEMG of biceps brachii during elbow flexion by measuring the maximum muscle strength and sEMG value of normal children and adults, and to analyze their sources, so as to lay a theoretical foundation for the method of motor program reconstruction to restore the function after brain injury, 30 healthy children aged 9 - 10 years and 30 adults aged 20 - 30 years were randomly selected. The muscle strength and sEMG of biceps brachii during elbow flexion were detected and recorded, and the data were statistically analyzed. The muscle strength of children was significantly lower than that of adults (P < 0.001), and the sEMG value of biceps brachii was significantly lower than that of adults (P < 0.001), but the sEMG value per kilogram force of children was significantly higher than that of adults (P < 0.01). The results show that there was a very significant difference in pull (efficiency) between adults and children when there was no significant difference in SEMG signal intensity. This is because although children’s central nervous system has matured, the muscle tissue has not been well trained, resulting in insufficient muscle strength. The muscle strength of adults is significantly higher than that of children, because they have been exercising for a long time after the development of the central nervous system. It is proved that sEMG signal is not produced by muscle contraction itself, but comes from the motor program signal of central nervous system which drives muscle contraction, and it is produced before muscle contraction.

A New Record of Kaloula(Amphibia: Anura: Microhylidae) in Shanghai, China

We discovered a medium-sized species of narrow-mouthed frog of the genus Kaloula in June and September 2014 during municipal surveys of amphibians in Shanghai. Three narrow-mouthed frogs were collected in city drains of the Binjiang Forest Park, Shanghai. Based on subsequent examination and morphological characters, these specimens were identified as Kaloula borealis（Barbour, 1908）. The species was mainly distributed in Northern China and Korea. It is a new amphibian record for Shanghai. We found the visible differences in male secondary sexual characteristics between our specimens and Beijing specimens. K. borealis was first described inhabiting urban greenlands which could benefit amphibian conservation in urban and urbanizing areas.

Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells

Abnormal expression of long interspersed element-1(LINE-1)has been implicated in drug resistance,while our previous study showed that chemotherapy drug paclitaxel(PTX)increased LINE-1 level with unknown mechanism.Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules(SGs).This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer(TNBC)cells.We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress,thereby adapting TNBC cells to chemotherapy drugs.Moreover,LINE-1 inhibitor efavirenz(EFV)could inhibit drug-induced SG to destabilize LINE-1.Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs.The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs.

The Impacts of Urbanization on the Distribution and Body Condition of the Rice-paddy Frog(Fejervarya multistriata) and Gold-striped Pond Frog(Pelophylax plancyi) in Shanghai,China

Previous studies have suggested that urbanization presents a major threat to anuran populations. However, very few studies have looked at the relationship between urbanization and anuran body condition. We investigated whether the distribution and body condition of the rice-paddy frog（Fejervarya multistriata） and gold-striped pond frog（Pelophylax plancyi） are influenced by increasing urbanization in Shanghai, China. Four study sites with six indicators of the major land-cover types were scored to indicate their position on an urbanization gradient. We found that both the density and body condition of F. multistriata declined significantly along this gradient. Although we observed a significant difference in body condition of P. plancyi among study sites with different degrees of urbanization, we did not find any corresponding significant differences in population density. Our results indicate that both the densities and body condition of these two anuran species show a negative relationship with increasing urbanization, but that the density of P. plancyi was only slightly affected in Shanghai.

Effect of doped Ni-Bi-B alloy on hydrogen generation performance of Al-InCl3

In this work,Ni-Bi-B alloy has been synthesized via chemical synthesis method.A new kind of Al-InCl3-(Ni-Bi-B)composite has been prepared by high energy mechanical ball grinding A1 powder with additives.Results show that the doped Ni-Bi-B alloy can significantly improve the hydrogen generation performance of Al-InCl3 and the catalytic activity is enhanced with the increasing content of Bi in Ni-Bi-B alloy.Under optimal conditions,the hydrogen generation yield and conversion yield of Al-InCl3-(Ni-Bi-B)reached1196.8 mL g^-1 and 100.0%at room temperature,respectively.Mechanism study shows five kinds of active sites,such as the fresh surface/defect of Al particle,Al-AlCl3,Al-In,Al-Bi/B and Al-Ni/B produced during the ball milling process.Their synergistic effect enhances the hydrogen generation performance of AlInCl3-(Ni-Bi-B)remarkably.In general,the proposed Al-InCl3-(Ni-Bi-B)composite is possible to serve as hydrogen generation material for fuel cells.

Resveratrol prevents interleukin-1 β-induced dysfunction of pancreatic β-cells

Objective：Interleukin-1β（IL-1β）plays an important role in the development of type 1 and type 2 diabetes mellitus.Resveratrol,a polyphenol,is known to have a wide range of pharmacological properties in vitro.In this research,we examined the effects of resveratrol on IL-1β-inducedβ-cell dysfunction.Methods：We first evaluated the effect of resveratrol on nitric oxide（NO）formation in RINm5F cells stimulated with IL-1βusing the Griess method.Next,we performed transient transfection and reporter assays to measure the transcriptional activity of peroxisome proliferator-activated receptor-γ（PPAR-γ）.We also used Western blotting analysis to assess the effect of resveratrol on inducible nitric oxide synthase（iNOS）expression and nuclear factor-κB（NF-κB）translocation to the nuclei in cells treated with IL-1β.In addition,we assessed the transcriptional activity of NF-κB using an electrophoretic mobility shift assay（EMSA）.Finally,we evaluated the effect of resveratrol on IL-1β-induced inhibition of glucose-stimulated insulin secretion in freshly isolated rat pancreatic islets.Results：Resveratrol significantly suppressed IL-1β-induced NO production,a finding that correlated well with reduced levels of iNOS mRNA and protein.The molecular mechanism by which resveratrol inhibited iNOS gene expression appeared to involve increased PPAR-γactivity,which resulted in the inhibition of NF-κB activation.Further analysis showed that resveratrol could prevent IL-1β-induced inhibition of glucose-stimulated insulin secretion in rat islets.Conclusion：In this study,we demonstrated that resveratrol could protect against pancreaticβ-cell dysfunction caused by IL-1β.

Follicular hyperandrogenism and insulin resistance in polycystic ovary syndrome patients with normal circulating testosterone levels

Polycystic ovary syndrome（PCOS） is a common reproductive disease with high heterogeneity. The role of excess androgen in PCOS etiology remains disputed, since around 20%-50% of PCOS women do not display hyperandrogenemia. The microenvironment of the ovary critically influences follicular development. In the present study, we assessed the role of androgen in PCOS by investigating whether excessive follicular fluid androgen was present in PCOS patients with normal serum androgen levels and influenced by follicular fluid insulin resistance（IR）.Follicular fluid samples of 105 women with PCOS and 105 controls were collected. Levels of steroid hormones,glucose and insulin in the follicular fluid were examined and compared with data from serum biochemistry tests. We found that 64.9%（63/97） of PCOS patients with normal serum androgen levels displayed abnormally high follicular fluid androgen level. The follicular fluid androgen level was positively correlated with follicular fluid IR within a certain range and follicular fluid estrogen-to-testosterone（E2/T） ratio was significantly reduced in these patients.These results indicated that there existed a subgroup of PCOS patients who displayed excessive follicular fluid androgen and IR despite their normal circulating testosterone（T） levels. Our study highlights the importance of ovary hyperandrogenism and IR in the etiology of PCOS.

Hybrid water electrolysis:Replacing oxygen evolution reaction for energy-efficient hydrogen production and beyond

Renewable energy-driven hydrogen generation from water electrolysis has been widely recognized as a promising approach to utilize sustainable energy resources,reduce our dependence on legacy fossil fuels and alleviate net carbon dioxide emissions.However,conventional water electrolyzers suffer from the high overpotentials,mainly due to the sluggish kinetics of anodic oxygen evolution reaction(OER).This reaction also generates reactive oxygen species that could degrade the proton exchange membrane and oxygen that may mix with the cathodic hydrogen to form explosive gaseous mixtures.To address these issues,an innovative hybrid water electrolysis strategy which involves a certain alternative oxidation reaction to replace OER has been developed,and has led to a burgeoning area that sparks much research interest in finding available alternative reactions and their corresponding electrocatalysts.Herein,we summarize the alternative reactions into three groups:(1)the reagentsacrificing type that can generate H2 with an ultra-low potential while the substrates are oxidized to valueless products;(2)the pollutant-degrading type at which environmental pollutants are used as substrates;(3)the valueadded type that produces valuable products at the anode.Catalyst and electrolyzer designs for hybrid electrolysis are also briefly discussed,with an emphasis on the catalyst reconstruction phenomenon.Finally,the present challenges and perspectives are put forward.

Preface to the special issue on electrocatalysis and electrosynthesis

Electrochemistry is an important branch of modern chemistry that studies the relationship between electrical energy and chemistry changes.Two actively pursued directions within this discipline are electrocatalysis and electrosynthesis,which are closely connected with different focuses and targets.The former is involved in many energy conversion technologies including fuel cells,water electrolyzers and metal-air batteries,while the latter enables the selective production of organic chemicals in a controlled fashion under mild conditions.

Nitrogen-doped carbon dots-modified Prussian blue with sandwichlike structure as a high-performance electrochromic material

Prussian blue(PB),as a promising inorganic electrochromic material(ECM),has been widely used in smart windows,displays,sensors,etc.However,there are still many challenges for PB to achieve high electrochromic performance.Herein,we synthesized nitrogen-doped carbon dots-modified PB film(defined as PB@N-CDs)with a sandwich-like structure by a simple stepwise electrodeposition method.The carbon dots show an obvious advantage in ultrafast electron transfer ability,which can reduce charge loss during the transfer process,improve the electrochemical activity on both sides of PB,and thus facilitate a rapid electrochromic response.Furthermore,the surface of nitrogen-doped carbon dots contains multiple organic functional groups,which widen the movement path of K+ions under electrostatic adsorption.Impressively,the PB@N-CDs film exhibits a short bleaching/coloring time(0.5/0.9 s)and a superior optical modulation range(78.6%).Particularly,the coloring efficiency has been significantly improved to 137.71 cm^(2)/C(at 700 nm).All of these results open up new avenues for developing highperformance PB-based ECMs and promoting their applications in corresponding electrochromic devices(ECDs)and smart windows.

Rapid,artifact-reduced,image reconstruction for super-resolution structured illumination microscopy

Super-resolution structured ilumination microscopy(SR-SIM)is finding increasing application in biomedical research due to its superior ability to visualize subcellular dynamics in living cells.However,during image reconstruction artifacts can be introduced and when coupled with time-consuming postprocessing procedures,limits this technique from becoming a routine imaging tool for biologists.To address these issues,an accelerated,artifact-reduced reconstruction algorithm termed joint space frequency reconstruction-based artifact reduction algorithm(JSFR-AR-SIM)was developed by integrating a high-speed reconstruc tion framework with a high-fidelity optimization approach designed to suppress the sidelobe artifact.Consequently,JSFR-AR-SIM produces high-quality,super-resolution images with minimal artifacts,and the reconstruction speed is increased.We anticipate this algorithm to facilitate SR-SIM becoming a routine tool in biomedical laboratories.

Homologous gradient heterostructure-based artificial synapses for neuromorphic computation

Gradient heterostructure is one of fundamental interfaces and provides an effective platform to achieve gradually changed properties in mechanics,optics,and electronics.Among different types of heterostructures,the gradient one may provide multiple resistive states and immobilized conductive fila-ments,offering great prospect for fabricating memristors with both high neuromorphic computation capability and repeatability.Here,we invent a memristor based on a homologous gradient heterostructure(HGHS),compris-ing a conductive transition metal dichalcogenide and an insulating homolo-gous metal oxide.Memristor made of Ta–TaS_(x)O_(y)–TaS 2 HGHS exhibits continuous potentiation/depression behavior and repeatable forward/backward scanning in the read-voltage range,which are dominated by multi-ple resistive states and immobilized conductive filaments in HGHS,respec-tively.Moreover,the continuous potentiation/depression behavior makes the memristor serve as a synapse,featuring broad-frequency response(10^(-1)–10^(5) Hz,covering 106 frequency range)and multiple-mode learning(enhanced,depressed,and random-level modes)based on its natural and moti-vated forgetting behaviors.Such HGHS-based memristor also shows good unifor-mity for 5?7 device arrays.Our work paves a way to achieve high-performance integrated memristors for future artificial neuromorphic computation.

Iodine-assisted ultrafast growth of high-quality monolayer MoS_(2) with sulfur-terminated edges

Two-dimensional(2D)semiconductors have attracted great attention to extend Moore’s law,which motivates the quest for fast growth of high-quality materials.However,taking MoS_(2) as an example,current methods yield 2D MoS_(2) with a low growth rate and poor quality with vacancy concentrations three to five orders of magnitude higher than silicon and other commercial semiconductors.Here,we develop a strategy of using an intermediate product of iodine as a transport agent to carry metal precursors efficiently for ultrafast growth of high-quality MoS_(2).The grown MoS_(2) has the lowest density of sulfur vacancies(~1.41×10^(12) cm^(−2))reported so far and excellent electrical properties with high on/off current ratios of 108 and carrier mobility of 175 cm^(2) V^(−1) s^(−1).Theoretical calculations show that by incorporating iodine,the nucleation barrier of MoS_(2) growth with sulfur-terminated edges reduces dramatically.The sufficient supply of precursor and low nucleation energy together boost the ultrafast growth of sub-millimeter MoS_(2) domains within seconds.This work provides an effective method for the ultrafast growth of 2D semiconductors with high quality,which will promote their applications.

Engineering trienzyme cascade-triggered fluorescent immunosensor platform by sequentially integrating alkaline phosphatase, tyrosinase and horseradish peroxidase

Mulit-enzyme cascades are a major type of chemical transformations and play a crucial role in biological signal transduction and metabolism. Herein, a trienzyme cascade-triggered fluorescent immunosensor platform was constructed by sequentially integrating alkaline phosphatase(ALP), tyrosinase(TYR)and horseradish peroxidase(HRP). The proposed platform was based on HRP-induced a rapid in situ fluorogenic reaction between dopamine(DA) and 1,5-dihydroxynaphthalene(DHA) to produce a strong yellow azamonardine fluorescent compound(AFC). The obtained AFC was clearly characterized by highresolution mass spectrum,1H NMR,^(13)C NMR and theoretical calculations. The integration of the twoenzyme system(TYR and HRP) or three-enzyme system(ALP, TYR and HRP) led to a maximum of 400.0-fold and 250.0-fold fluorescence enhancements, respectively. Using cardiac troponin I(c Tn I) as the model antigen, a trienzyme cascade-triggered fluorescent immunosensor platform was developed for quantitative detecting c Tn I in a wide linear range from 2 ng/m L to 150 ng/m L with a detection limit of 0.67ng/m L. In addition, the proposed platform was successfully applied in detection of c Tn I in serum of clinical patients. Overall, the developed fluorescent immunosensor performs powerful implications for researching enzyme cascade systems in the field of biomedicine.

Rogue wave solutions of (3+1)-dimensional Kadomtsev-Petviashvili equation by a direct limit method

On the bases of N-soliton solutions of Hirota’s bilinear method,high-order rogue wave solutions can be derived by a direct limit method.In this paper,a(3+1)-dimensional Kadomtsev-Petviashvili equation is taken to illustrate the process of obtaining rogue waves,that is,based on the long-wave limit method,rogue wave solutions are generated by reconstructing the phase parameters of N-solitons.Besides the fundamental pattern of rogue waves,the triangle or pentagon patterns are also obtained.Moreover,the different patterns of these solutions are determined by newly introduced parameters.In the end,the general form of N-order rogue wave solutions are proposed.

Preparation of spatially uniform monolayer FeSexTe1−x(0

Spatially uniform high-temperature superconducting films are highly desirable for exploring novel properties and popularizing applications.To improve the uniformity,we fabricate monolayer FeSexTe1−x(0<x≤1)films on SrTiO3(001)by topotactic reaction of monolayer FeTe films with selenium.Using in situ low-temperature scanning tunneling microscopy/spectroscopy,we demonstrate atomic-level uniformity of element distribution and well-defined superconducting gaps of~15 meV in FeSexTe1−x films.In particular,the monolayer FeSe films exhibit fewer line defects and higher superfluid density as evidenced by sharper coherence peaks than those prepared by the co-evaporation method.Our results provide a promising way to optimize sample quality and lay a foundation for studying new physics and drawing reliable conclusions.

High-speed image reconstruction for optically sectioned,super-resolution structured illumination microscopy

Super-resolution structured illumination microscopy(SR-SIM)is an outstanding method for visualizing the subcellular dynamics in living cells.To date,by using elaborately designed systems and algorithms,SR-SIM can achieve rapid,optically sectioned,SR observation with hundreds to thousands of time points.However,real-time observation is still out of reach for most SIM setups as conventional algorithms for image reconstruction involve a heavy computing burden.To address this limitation,an accelerated reconstruction algorithm was developed by implementing a simplified workflow for SR-SIM,termed joint space and frequency reconstruction.This algorithm results in an 80-fold improvement in reconstruction speed relative to the widely used Wiener-SIM.Critically,the increased processing speed does not come at the expense of spatial resolution or sectioning capability,as demonstrated by live imaging of microtubule dynamics and mitochondrial tubulation.

The characteristics of the structure, strain and kinematic vorticity of the Wulian detachment fault zone, Shandong Peninsula, China

As one of the vital tectonic units of the Wulian Metamorphic Core Complex(MCC), the Wulian detachment fault zone(WDFZ), which developed in the Jiaodong peninsula, separates the lower plate of the ultrahigh pressure(UHP) metamorphic rocks in the Sulu orogenic belt from the upper plate of the early Cretaceous Zhucheng basin and the basin basement. The fault zone generally strikes NNE with a dip in the west along the southern portion of the MCC and strikes NE with a dip in the WNWalong the northern portion. The fault zone displays a wavy-tile-shaped extension on the plane, principally composed of the fault breccias and mylonite and transits downward to the mylonitic gneiss. As a whole, the detachment fault zone shows a top-towest or a WNW extension. By calculating the harmonic mean, we obtain a Flynn index K of 0.98–2.0, and the mean value is approximately 1.35 in the fault zone. According to the polar Mohr construction, the extensional crenulation cleavage, the RS/θ,and the quartz C-axial fabric methods, we acquire mean kinematic vorticity values of 0.64–0.97, 0.76–0.93, 0.6–0.92, and 0.63–0.98 with mean values of 0.83, 0.80, 0.78 and 0.86, respectively, for mylonite and promylonite. The strain measurement results and the kinematic vorticity values indicate that the WDFZ is a normal ductile shear zone developed in the extensional setting.The kinematic track shows that the kinematic vorticity value decreases gradually from the NW to the SE as a whole. A simple shear dominates in the middle and upper parts of the shear zone, which is reflected by a higher vorticity value(>0.75, up to 0.98),a low thinning rate and a lower K value. In contrast, toward the footwall, the pure shear is increased significantly, showing a lower vorticity value(<0.70, low to 0.64), a relatively high thinning rate and a higher K value. Combined with the geotectonic background, the development and evolution of the WDFZ should respond to lithospheric thinning and the destruction of the North China Craton(NCC). As a result, the WDFZ can be defined as a thinning normal shear zone developed in the extension tectonic setting and the combined result of the simple shear caused by the crust extension and pure shear led by the rapid uplift of the footwall and magmatic upwelling.