A novel single-base deletion of the RUNX Family Transcription Factor 2 gene associated with cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is a rare, autosomal dominant hereditary disorder characterized by skeletal malformations and dental abnormalities. The purpose of this study was to explore the functional role of a novel mutation in the pathogenesis of CCD. Genomic DNA was extracted from peripheral blood mononuclear cells collected from family members of a Chinese patient with CCD. An analysis of their RUNX Family Transcription Factor 2 (RUNX2) gene sequences was performed by PCR amplification and Sanger sequencing. The function of the mutant RUNX2 was studied by bioinformatics, real-time PCR, western blotting, and subcellular localization analysis. Sanger sequencing identified a novel single-base deletion (NM_001024630.4:c.132delG;NP_001019801.3: Val45Trpfs* 99) in the RUNX2 gene present in the Chinese patient with CCD. In vitro, functional studies showed altered protein localization and increased expression of mutant RUNX2 mRNA and mutant Runt-related transcription factor 2 (RUNX2). Luciferase reporter assay demonstrated that the novel RUNX2 mutations significantly increased the transactivation activity of RUNX2 on the osteocalcin gene promoter. In conclusion, we identified a patient with sporadic CCD carrying a novel deletion/frameshift mutation of the RUNX2 gene and performed screening and functional analyses to determine the cause of the CCD phenotype. This study provides new insights into the pathogenesis of CCD.3.

In Situ Construction of a Liquid Film Interface with Fast Ion Transport for Solid Sodium-Ion Batteries.

Solid sodium-ion batteries (SSIBs) are considered as one of the promising energy storage systems because of their high safety and high energy density. However, the sodium metal anode presents poor wettability with a solid electrolyte, resulting in high interface impedance and dendrite growth, which severely limits their application in practice. Herein, a novel liquid film (Na-BP) interface is constructed between sodium and solid electrolyte (Na3Hf2Si2PO12) with an excellent kinetic mass transfer ability and good fluidity, which could guarantee a close contact and fast charge transfer at interface. The symmetric cells with the designed interface show a high-rate and long-cycle performance and could cycle stably more than 1000 and 700 h at 0.2 and 0.5 mA cm-2, respectively. The critical current density of the cells can reach 3.6 mA cm-2 at room temperature, which is the highest value in similar works.

Blockade of IL-6 inhibits tumor immune evasion and improves anti-PD-1 immunotherapy.

Long-standing inflammatory bowel disease predisposes to the development of colorectal cancer (CRC). Interleukin (IL) -6, a pivotal link between chronic inflammation and tumor progression, has recently been recognized as a potential therapeutic target. The effect of IL-6 on proliferation and metastasis of CRC by activating the STAT3 pathway has been widely demonstrated in recent years, but few on mediating tumor immune evasion. In this study, we found that IL-6 was remarkably overexpressed in CRC and its elevation was associated with a poor prognosis. We studied CRC tumorigenesis in vivo by inoculating MC38 tumors and induced-CRC model via AOM/DSS (azoxymethane/dextransulfate sodium) in IL-6 deficient (IL-6-/-) and wild-type (WT) mice and found that IL-6-/- mice were less susceptible to develop tumors, compared to WT mice. We detected CD8+ T cells via immunofluorescence and found they exhibit high expression in tumor of IL-6-/- mice. High level of IL-6 was found in colitis model, with down-regulation of MHC-I molecules. In in vitro experiments, we found that IL-6 may act as a negative regulator in IFNγ-STAT1-MHC-I signaling. In addition, vivo trials also confirmed that MHC-I mRNA level was negatively related to the existence of IL-6. Furthermore, the blockade of IL-6 also activated CD8+T-cell accumulation and led to the high PD-L1 expression in CRC, which can sensitize animals to anti-PD-1 therapy. Our study provides a research basis for the significant role of IL-6 in tumor evasion and highlights a novel target to improve the efficacy of immunotherapy.

CYP2J2/EET reduces vulnerability to atrial fibrillation in chronic pressure overload mice.

Growing evidence has well established the protective effects of CYP2J2/EET on the cardiovascular system. The aim of the present study was to determine whether CYP2J2/EET has a preventive effect on atrial fibrillation (AF) and to investigate the underlying mechanisms. Wild-type mice were injected with or without AAV9-CYP2J2 before abdominal aortic constriction (AAC) operation. After 8 weeks, compared with wild-type mice, AAC mice display higher AF inducibility and longer AF durations, which were remarkably attenuated with AAV9-CYP2J2. Also, AAV9-CYP2J2 reduced atrial fibrosis area and the deposit of collagen-I/III in AAC mice, accompanied by the blockade of TGF-ß/Smad-2/3 signalling pathways, as well as the recovery in Smad-7 expression. In vitro, isolated atrial fibroblasts were administrated with TGF-ß1, EET, EEZE, GW9662, SiRNA Smad-7 and pre-MiR-21, and EET was demonstrated to restrain the differentiation of atrial fibroblasts largely dependent on Smad-7, due to the inhibition of EET on MiR-21. In addition, increased inflammatory cytokines, as well as activated NF-κB pathways induced by AAC surgery, were also significantly blunted by AAV9-CYP2J2 treatment. These effects of CYP2J2/EET were partially blocked by GW9662, the antagonist of PPAR-γ. In conclusion, this study revealed that CYP2J2/EET ameliorates atrial fibrosis through modulating atrial fibroblasts activation by disinhibition of MiR-21 on Smad-7, and attenuates atrial inflammatory response by repressing NF-κB pathways, reducing the vulnerability to AF, and CYP2J2/EET exerts its role at least partially through PPAR-γ activation. Our findings might provide a novel upstream therapeutic strategy for AF.

Design of spherical aberration free liquid-filled cylindrical zoom lenses over a wide focal length range based on ZEMAX.

A systematic design idea for liquid-filled cylindrical zoom lenses with ideal imaging quality over a wide focal length range is introduced in detail. The PWC method is used to calculate the initial structure parameters of the zoom lenses, and the optical design software ZEMAX is used to eliminate the spherical aberration at different focal lengths. Lenses named SLCL-Doublet are finally designed, which are formed by a symmetric liquid-core cylindrical lens (SLCL) filled with variable refractive index (RI) liquid and a doublet cylindrical lens capable of significantly weakening the spherical aberration. The focal length of the SLCL-Doublet continuously decreases from 101.406 mm to 54.162 mm as the liquid RI changes from 1.3300 to 1.5000. Calculated over 75% of the full aperture, the root mean square (RMS) spot radius of the SLCL-Doublet is always less than 7 µm over the whole focal length range, and the peak-to-valley wavefront error remains below the λ/4 limit when the focal length ranges from 62.373 mm to 65.814 mm, within which the lenses approach the diffraction limit, demonstrating improvement in the optical performance over that of previously designed liquid-core cylindrical lenses. The sources of potential fabrication and installation errors in the practical implementation of the SLCL-Doublet are also analyzed in detail. The SLCL-Doublet is demonstrated to be characterized by high imaging quality and easy installation, which enriches the types of core optical element for measuring the liquid RI and liquid diffusion coefficient and provides guarantee for improving the measurement accuracy.

A New Spiropyran-Based Sensor for Colorimetric and Fluorescent Detection of Divalent Cu2+ and Hg2+ Ions and Trivalent Ce3+, Cr3+ and Al3+ Ions.

A new spiropyran derivative acts as colorimetric and fluorescent sensor for metal ions. Addition of Cu2+, Al3+, Cr3+ and Ce3+ to the sensor solution brings about marked increase in the absorption intensities while addition of other metal ions (Na+, K+, Li+, Sr2+, Hg2+, Zn2+, Co2+, Ni2+ and Ag+) fails to cause substantial change in the UV-Vis spectra. The sensor can be used for detection of Hg2+, Cu2+, Ce3+, Cr3+ and Al3+ ions by the naked eye and by fluorescence enhancement. The detection limit of Cu2+ and Hg2+ ions by the sensor is estimated to be 10 and 14 µM, respectively. Job's plot analysis on the sensor-Cu2+ complexation reveals the formation of a 2:1 stoichiometric complex between the sensor and Cu2+ ion.

The association between liver cirrhosis and fracture risk: A systematic review and meta-analysis.

OBJECTIVE: Liver cirrhosis (LC) was associated with an increased risk of osteoporosis; however, the association between LC and fracture risk was inconclusive. Therefore, this systematic review and meta-analysis aims to explore the association between LC and fracture risk. DESIGN: To identify related literature, a systematic search of PubMed, EMBASE, Web of science and the Cochrane Library from 1965 to July 2017 without language limitation was performed. The random-effects model described by DerSimonian and Laird was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Eventually, 5 cohort and 3 case-control studies were identified, which included 321 035 subjects and 31 272 fracture cases. The pooled OR of the association between LC and any fracture risk, hip fracture, spine/trunk fracture and limb fracture was 1.94 (95% CI, 1.59-2.37), 2.11 (95% CI, 1.34-3.32), 2.00 (95% CI, 1.50-2.67) and 1.82 (95% CI, 1.65-2.01), respectively. CONCLUSION: In conclusion, this study indicates that cirrhotic patients have an increased risk of fracture. Preventive measures should be instituted as early as possible.

Double liquid-core cylindrical lens utilized to measure liquid diffusion coefficient.

We design and fabricate an aplanatic double liquid-core cylindrical lens (DLCL), which is used to measure the binary liquid diffusion coefficient (D). The front lens of the DLCL is used as both a diffusion cell and a key imaging element; the refractive index (RI) of liquid filled in its core can be measured in the way of spatial resolution. The rear lens of the DLCL is used as an aplanatic component, and either the RI position of spherical aberration (SA) or the SA in a range of RI caused by the front lens can be regulated by selecting the liquid, of which RI is pre-prepared and filled in the rear liquid core. Equipped with the aplanatic DLCL, two methods have been applied to measure the D value of 0.33mol/L KCL aqueous solution at temperature 298.15K. The first method derives D value precisely from the drift rate of diffusion image and the measured D is 1.8508 × 10-5 cm2/s. Meanwhile, the second method obtains the D value rapidly by analyzing an instantaneous diffusion image and the measured D is 1.8619 × 10-5 cm2/s. The measured values are in good agreement with the literature value, demonstrating that the designed DLCL works well in measuring liquid diffusion coefficients.

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides.

An efficient palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides has been developed. The reaction proceeds under mild reaction conditions with high efficiency and excellent functional group tolerance, even towards formyl and hydroxy groups. Preliminary mechanistic studies reveal that a secondary trifluoromethylated alkyl radical is involved in the reaction.

New method to measure liquid diffusivity by analyzing an instantaneous diffusion image.

A novel optical method was applied to measure the binary liquid diffusion coefficient (D) quickly. Equipped with an asymmetric liquid-core cylindrical lens (ALCL), the spatially resolving ability of the ALCL in measuring refractive index of liquid was utilized to obtain the gradient distribution of the liquid concentration along diffusive direction. Based on Fick's second law, the D value was then calculated by analyzing diffusion images. It was worth mentioning that only one instantaneous diffusive image was required to measure D value by the method, reducing the measurement time greatly from several hours in traditional methods to a few seconds. The diffusion coefficients of ethylene glycol diffusing in pure water, at temperatures from 288.15 to 308.15 K, were measured by analyzing instantaneous diffusion images, the results were consistent well with the values measured by using holographic interferometry and Taylor dispersion methods. The method is characterized by faster measurement, direct observation of diffusive process, and easy operation, which provides a new method in measuring diffusion coefficient of liquids rapidly.

Demonstration of polarization mode selection and coupling efficiency of optofluidic ring resonator lasers.

We demonstrate the polarization mode selection and the dependence of coupling efficiency on polarization state of pump light for an optofluidic ring resonator (OFRR) laser. An optical fiber is chosen to serve as the ring resonator and surrounded by rhodamine 6G dye solution of lower refractive index as the fluidic gain medium. When the ring resonator is pumped by a linearly s-polarized laser, the emitted whispering gallery mode (WGM) lasing is of parallel polarization (TM mode), while p-polarized laser excitation generates a vertically polarized lasing emission (TE mode), both TM and TE mode lasing emission coexist simultaneously if the ring resonator is pumped by the s- and p-mixed polarized light. Further investigation reveals that the lasing intensity of the TM mode is approximately twice that of the TE mode for the same pump energy density, meaning an obvious difference of coupling efficiency on the polarization state of pump light; the experimental results of coupling efficiency are well explained by an induced dipole model.

New energy vehicles' technology innovation coordination strategy based on alliance negotiation under dual credit policy.

The development of new energy vehicles (NEVs) is one of the effective ways to alleviate carbon emissions, environmental pollution, and energy scarcity in the transportation sector. The Chinese government has innovatively proposed the "dual credit policy," but it is still a hot topic whether it can promote the NEVs' technological innovation. In this study, we construct game models and obtain the technological innovation strategies for NEVs under the dual credit policy, considering that the NEV supply chain contains one manufacturer and N suppliers. Further, we construct bargaining game models and study how to encourage manufacturers and suppliers to enhance technological innovation, realize supply chain coordination, and give the alliance strategy to maximize suppliers' profit. We found that the dual credit policy can effectively stimulate technological innovation, and the higher the credit price or technological innovation credit factor, the higher the technical level of NEVs. The findings could guide the government to adjust and revise the policy. Second, we found that the bargaining games could coordinate the NEV supply chain so that decentralized enterprises can achieve optimal technological innovation under centralized decision-making. Third, we found that suppliers can improve their profits by choosing a suitable alliance strategy under the manufacturer's different negotiating power.

The allocative efficiency of construction land quota in rural China: a perspective of bidders' behavior and regret psychology.

The construction land quota pricing mechanism with cost plus pricing method is not sufficient to reflect its intrinsic value. This diminishes the willingness of farmers to voluntarily reclaim abandoned residential and other rural construction land, leading to suboptimal efficiency in rural land utilization and an excessive squandering of rural land resources. Thus, a sequential auction model with two stages for complementary goods was constructed, which considered the synergic characteristics between the land and quota. Further, regret psychology of bidder was considered in the case of winning or losing. A rational pricing mechanism has been developed to allocate construction land quotas, aiming to enhance farmers' motivation to the vacant homesteads of reclamation and revitalizing the stock of rural construction land. The results revealed that the regret psychology in the case of winning would decrease the transaction price of the quota, i.e., the greater the perceived regret in the case of winning, the more significant the reduction in the bidding price offered. Moreover, the regret psychology in the event of losing/failure would increase the transaction price of quota. Furthermore, publishing only the winner's price after the auction leads to the highest price of the quota offered by the bidder. In contrast, publishing only the loser's bidding price leads to the lowest transaction price of the quota offered by the bidder. In addition, the fee for delayed construction would increase the bidding price of the construction land quota. Therefore, local governments should consider announcing only the winner of price after the quota auction has ended. In addition, imposing a fee for delayed construction would enhance the transaction price of land quota, increase farmers' revenue from land reclamation, and incentivize farmers to reclaim unused rural land.

Hindrance or facilitator? The economic consequences of national demonstration eco-industrial parks in China.

Many countries attach great importance to the green, low-carbon, and circular development of industrial parks. China is one of them and has entered an exploration journey of national demonstration eco-industrial parks (NDEIPs). However, the impact of the transformation of industrial parks into NDEIPs on local economic development still remains a mystery. To address this issue, we develop an empirical study using a combination of the multi-period difference-in-differences method and the propensity score matching method based on the panel data for 266 cities in China from 2001 to 2021. The results show that industrial parks becoming NDEIPs promotes cities' economic development. This conclusion still holds after a series of robustness tests, such as the reverse causality test and the placebo test. Moreover, the park heterogeneity tests show that the economic consequences vary according to differences in levels, industry types, life cycle phases, and the degree of foreign firm agglomeration. The city heterogeneity tests show that the economic consequences differ based on administrative levels, innovation capabilities, technology industrialization, and environmental friendliness. The spatial heterogeneity tests show that the economic consequences differ according to geographical location and whether situated in the Yangtze River Economic Belt. The policy upgrading heterogeneity tests show that the economic consequences differ during the process of policy upgrading and transformation. In addition, the mechanism tests reveal that green innovation, human capital level, and firm attractiveness mediate the relationship between industrial parks becoming NDEIPs and cities' economic development. This study provides a new perspective for understanding the economic effects of the transformation of industrial parks into NDEIPs, and provides a reference for the government on how to maximize these economic effects.

Study of reactive dyes and their hydrolyzed forms in a real trichromatic dyeing process by capillary electrophoresis with UV detection.

Detecting the concentration of reactive dyes and their hydrolyzed products is essential for controlling the dyeing process and is an important guide for upgrading and improving textile dyeing technology. In this study, capillary electrophoresis (CE) with UV detection was for the first time applied in a real trichromatic dyeing process to provide qualitative and quantitative determination of reactive dyes and their hydrolyzed forms. Here, three original reactive dyes (SES-Cl-red-195, SES-Cl-yellow-145, and SES-Cl-blue-194), their vinyl sulfone forms (VS-Cl-red-195, VS-Cl-yellow-145, and VS-Cl-blue-194), and complete hydrolyzed forms (HES-OH-red-195, HES-OH-yellow-145, and HES-OH-blue-194) could be baseline separated in our developed BGE comprised of 10.0 mol/L Na2B4O7, 15% (V/V) ACN at pH 8.50 that adjusted by 0.50 mol/L H3BO3. The LODs (S/N = 3) of nine analytes ranged from 0.3 to 1.3 mg/L, and high sensitivities were achieved with UV detection. The RSDs of peak area and migration time were in the ranges of 1.4-3.8% and 0.39-1.29%, which indicated the CE methods were reliable for studying different dye forms in complex dye baths, and for evaluating dyeing process quality. Thus, the percentage of dye-uptake in single and trichromatic combination dyes was calculated based on the concentration of the original and their vinyl sulfone and hydrolyzed forms, and the result was consistent with the traditional UV-Vis method.

Procedural arrhythmia termination and long-term single-procedure clinical outcome in patients with non-paroxysmal atrial fibrillation.

BACKGROUND: The influence of procedural arrhythmia termination on long-term single-procedure clinical outcome in patients with non-paroxysmal atrial fibrillation (AF) remains controversial. METHODS: An individualized stepwise ablation strategy was used in 200 consecutive patients with non-paroxysmal AF who underwent first-time radiofrequency catheter ablation, with pulmonary vein isolation and sinus rhythm (SR) restoration as the primary endpoints. RESULTS: SR was restored by ablation in 94 patients, including 32 with AF directly and 62 with intermediate atrial tachycardia (AT). Cardioversion was performed to restore SR in 106 patients, including 31 with intermediate AT, and 75 with sustained AF. During a mean follow-up of 50.0 ± 9.3 months, single-procedure success was achieved in 99 (49.5%) patients. There was a significant difference in long-term success between patients with SR restoration by ablation and by cardioversion (63.8% vs 36.8%; P < 0.001), but not between patients with AF termination by ablation and by cardioversion (53.6% vs 42.7%; P = 0.146). SR restoration by ablation (odds ratio = 3.032; 95% confidence interval = 1.703-5.398; P < 0.001) was the only predictor of single-procedure success by logistic regression analyses. In patients with intermediate AT (n = 93), AT termination by ablation was associated with a higher success rate than AT termination by cardioversion (62.9% vs 22.6%; P < 0.001). CONCLUSIONS: SR restoration and AT termination by ablation were both associated with an improved long-term single-procedure clinical outcome in patients with non-paroxysmal AF.

Artificial porous heterogeneous interface for all-solid-state sodium ion battery.

Solid sodium-ion batteries are regarded as promising candidates for next-generation energy storage systems with high energy density and good safety. However, the large interface resistance and dendrite growth between sodium and solid electrolytes, especially at high current densities, severely limits their development. Herein, an artificial porous heterogeneous interface is constructed between sodium and the NASICON electrolyte Na3Hf2Si2PO12 (NHSP). This indicated that the porous heterogeneous interface with high-efficiency ion-electron transfer properties could effectively reduce the interface resistance, inhibit dendrites, and realize good rate performance. The symmetric cell with porous heterogeneous interface could cycle stably for more than 2000 h at 0.2 mA cm-2 at room temperature, and the critical current density reached 2.7 mA cm-2. Our study provides a promising direction for creating a stable interface that meets both the long-cycle and high-rate requirements for all-solid-state sodium-ion batteries.

Right ventricular outflow pacing induces less regional wall motion abnormalities in the left ventricle compared with apical pacing.

AIMS: This study aimed to explore if the right ventricular outflow tract (RVOT) pacing is superior to right ventricular apical (RVA) pacing on the overall left ventricular (LV) function and regional wall motion. METHODS AND RESULTS: Sixty patients with atrio-ventricular (AV) block and normal ejection fraction undergoing dual-chamber pacemaker implantation were randomized to permanent ventricular stimulation either in the RVOT or the RVA. Left ventricular volume, ejection fraction, and LV regional wall motion were assessed by echocardiography. Right ventricular apical pacing had prolonged QRS duration, compared with RVOT pacing (154.1 ± 26.5 vs. 120.9 ± 22.3, P< 0.05). There were also significant differences in LV pre-ejection interval and interventricular mechanical delay (IVMD) at 12-month follow-up between the two groups, but none in the LV volume, left ventricular ejection fraction, and index of systolic synchrony (Ts-SD). During RVA pacing, the average peak systolic velocity (Sm) of 12 LV segments [3.5, 95% confidence interval (CI) 3.2-3.8 cm/s] had a trend of being lower compared with RVOT pacing (3.9, 95% CI 3.5-4.1 cm/s) (P= 0.09). Further analysis showed that the Sm at the inferior wall and posterior-septum wall was significantly decreased during RVA pacing compared with RVOT pacing. There were no significant differences for other LV segments. CONCLUSION: The RVOT pacing in AV block patients over 1 year may be superior to RVA pacing in terms of regional LV performance, LV global electromechanical delay, and IVMD, although intraventricular dyssynchrony and LV volumes do not differ. Larger trials with clinical endpoints are warranted to conclusively define the advantages of RVOT or RV septal pacing.

Blocking the pulmonary vein to left atrium conduction in addition to the entrance block enhances clinical efficacy in atrial fibrillation ablation.

BACKGROUND: The unidirectional pulmonary vein (PV) to left atrium (LA) conduction after achieving PV entrance block has not been evaluated. METHODS: Circumferential PV isolation was performed in 573 consecutive patients with atrial fibrillation (AF). The unidirectional PV to LA conduction and its influence on clinical outcomes were evaluated. RESULTS: A total of 341 ipsilateral PVs (29.7%) with spontaneous activities (SAs) were documented in 231 patients (40.3%). The unidirectional PV to LA conduction was confirmed in 11 ipsilateral PVs (3.2%) of 11 patients (4.8%). Patients were classified to three groups: Group A (had unidirectional PV to LA conduction during SAs), Group B (with SAs but without PV to LA conduction), and Group C (without SAs). During a 30-minute observation, the reconnection incidence was higher in Group A (45.4%) than in Group B (13.9%, P = 0.042) and Group C (11.5%, P = 0.018). The reconnection time was shorter in Group A (10.8 ± 9.8 minutes) than that in Group B (20.7 ± 8.0 minutes, P = 0.037) and Group C (21.2 ± 8.2 minutes, P = 0.022). All 11 PVs were successfully isolated and bidirectional block was achieved. CONCLUSION: Unidirectional entrance block with SAs in PVs may not be a good indication of complete PV isolation. Bidirectional block of the PV-LA junction can reduce the acute PV reconnection and may reduce the chronic AF recurrence in patients undergoing circumferential PV isolation.

Development of a Personalized Recommendation System for E-Commerce Products for Distributed Storage Systems.

Because the distributed storage system is based on network technology, it can store data in multiple independent low-cost physical storage devices, and it is also suitable for large-capacity storage, so it has become more and more popular. Today, common applications of distributed storage systems include cloud storage services, data center storage services, and P2P storage services. Typical ones are GFS, HDFS, OceanStore, and Dynamo. Due to regional and economic differences, the development level of global e-commerce (b2c) is very inconsistent. b2c contains the following key tags: buying and selling, which is the core of the website platform. E-commerce provides business users with transparent information and high-quality cheap products. Logistics is the basic guarantee for customers to execute transactions, and it is also a strict indicator of the website platform. There will be many visits during the operation of the e-commerce system, and the number of users in the early stage will increase exponentially. A safe and efficient e-commerce system can provide users with one-stop transaction support and convenient transaction processes. The personalized recommendation system has formulated some rules for certain fields, based on these rules, and defined certain types of knowledge for certain items to meet the needs of certain users and use the defined reasoning rules to generate recommendation results.