A facile and scalable method to synthesize PEGylated PDMAEMA for gene delivery.

In recent years, cationic polymer vectors have been viewed as a promising method for delivering nucleic acids. With the advancement of synthetic polymer chemistry, we can control chemical structures and properties to enhance the efficacy of gene delivery. Herein, a facile, cost-effective, and scalable method was developed to synthesize PEGylated PDMAEMA polymers (PEO-PDMAEMA-PEO), where PEGylation could enable prolonged polyplexes circulation time in the blood stream. Two polymers of different molecular weights were synthesized, and polymer/eGFP polyplexes were prepared and characterized. The correlation between polymers' molecular weight and physicochemical properties (size and zeta potential) of polyplexes was investigated. Lipofectamine 2000, a commercial non-viral transfection reagent, was used as a standard control. PEO-PDMAEMA-PEO with higher molecular weight exhibited slightly better transfection efficiency than Lipofectamine 2000, and the cytotoxicity study proved that it could function as a safe gene vector. We believe that PEO-PDMAEMA-PEO could serve as a model to investigate more potential in the gene delivery area.

Magnetic leakage behavior assessment in pipeline stress-concentrated areas using improved force-magnetic coupling model.

Magnetic flux leakage (MFL) technology is remarkable for its capability to detect pipeline geometric deformation and general corrosion defects. However, it cannot characterize the MFL behavior in stress-concentrated areas, thereby greatly challenging the subsequent pipeline maintenance. This study suggests that the MFL characteristics of pipeline in stress-concentrated areas are caused by the combined effect of the face magnetic charge on the deformed end-face and the body magnetic charge of the dislocation stack. In addition, an improved force-magnetic coupling model of the pipeline in stress-concentrated areas is established based on the magnetic dipole model and Jiles-Atherton (J-A) theory. In the verification experiment, the Q235 steel plate is magnetized along the extension direction (axis of the pipeline) through the solenoid coil to obtain the distribution law of the MFL signal in the stress-concentrated area under different excitation intensities. The results show that with the increase in excitation intensity, the deformation of the MFL field signal caused by the end-face of the stress-concentrated area gradually increases to a stable state. Moreover, the internal stress of the MFL field signal generated by the pipe dislocation rapidly increases to a peak value and then decays exponentially to a certain base value. The overall change trend is in good agreement with the calculation results of the established force-magnetic coupling model. Meanwhile, the differentiation research between deformation and internal stress MFL field signals under different magnetic field intensities can provide a reliable theoretical basis for the subsequent accurate identification and quantification of pipeline stress-concentrated areas.

Record-High T_{c} and Dome-Shaped Superconductivity in a Medium-Entropy Alloy TaNbHfZr under Pressure up to 160 GPa.

Superconductivity has been one of the focal points in medium and high-entropy alloys (MEAs-HEAs) since the discovery of the body-centered cubic (bcc) HEA superconductor in 2014. Until now, the superconducting transition temperature (T_{c}) of most MEA and HEA superconductors has not exceeded 10 K. Here, we report a TaNbHfZr bulk MEA superconductor crystallized in the BCC structure with a T_{c} of 15.3 K which set a new record. During compression, T_{c} follows a dome-shaped curve. It reaches a broad maximum of roughly 15 K at around 70 GPa before decreasing to 9.3 K at 157.2 GPa. First-principles calculations attribute the dome-shaped curve to two competing effects, that is, the enhancement of the logarithmically averaged characteristic phonon frequency ω_{log} and the simultaneous suppression of the electron-phonon coupling constant λ. Thus, TaNbHfZr MEA may have a promising future for studying the underlying quantum physics, as well as developing new applications under extreme conditions.

Clinical Value of the Diagonal Earlobe Crease in Patients with Chest Pain for Diagnosing Coronary Heart Disease.

Purpose: To investigate the clinical application value of diagonal earlobe crease (DELC) in patients with chest pain for the diagnosis of coronary heart disease (CHD) and to construct a risk model by multivariate logistic regression. Patients and Methods: Our trial enrolled prospectively and consecutively 706 chest pain patients with suspected CHD between January 2021 to June 2023 from Chengde Central Hospital. According to coronary angiography results, they were categorized into the CHD (n=457) and non-CHD groups (n=249). Results: The trial demonstrated a significant positive relationship between DELC and CHD. Independent risk factors were sex, age, hypertension, diabetes mellitus, LP (a), Cys C, and DELC, whilst HDL-C was a protective factor, for CHD. Patients with-DELC were older than those in the without-DELC arm (P<0.001) and had a higher proportion of males than females (61.6% vs 50.0%, P=0.026). After multifactorial correction, independent risk factors for CHD included DELC (OR=1.660, 95% CI:1.153 to 2.388, P=0.006), age (OR=1.024, 95% CI:1.002 to 1.045, P=0.030), gender (OR=1.702, 95% CI:1.141 to 2.539, P=0.009), hypertension (OR=1.744, 95% CI:1.226 to 2.482, P=0.002), diabetes mellitus (OR=2.113, 95% CI:1.404 to 3.179, P<0.001), LP(a) (OR=1.010, 95% CI:1.003 to 1.017, P=0.005), Cys C (OR=3.549, 95% CI:1.605 to 7.846, P=0.002). The Hosmer and Lemeshow (H-L) test (P=0.818) suggests a high goodness of fit, and the area under the ROC curve was calculated to be 0.721 (95% CI:0.682 to 0.760, P<0.001), which demonstrates that the model has a superior diagnostic value for CHD. Conclusion: DELC is an independent risk factor for CHD after adjusting for sex, age, hypertension, diabetes mellitus, smoking index, LP (a), Cys C, and HDL-C. Our model can be used clinically for assessing the risk of CHD.

Strain engineering improves the photovoltaic performance of carbon-based hole-transport-material free CsPbIBr2 perovskite solar cells.

Alkylamines with different chain lengths including n-butylamine, n-hexylamine, and n-octylamine, are applied to regulate the CsPbIBr2 perovskite film quality by strain engineering. The status of residual strains is controllably modulated, resulting in improved efficiency and stability of carbon-based hole-transport-material free CsPbIBr2 perovskite solar cells.

Healing the Buried Interface by a Plant-Derived Green Passivator for Carbon-Based CsPbIBr2 Perovskite Solar Cells.

Perovskite solar cells (PSCs) have attracted extensive attention in photovoltaic applications owing to their superior efficiency, and the buried interface plays a significant role in determining the efficiency and stability of PSCs. Herein, a plant-derived small molecule, ergothioneine (ET), is adopted to heal the defective buried interface of CsPbIBr2-based PSC to improve power conversion efficiency (PCE). Because of the strong interaction between Lewis base groups (-C═O and -C═S) in ET and uncoordinated Pb2+ in the perovskite film from the theoretical simulations and experimental results, the defect density of the CsPbIBr2 perovskite film is significantly reduced, and therefore, the nonradiative recombination in the corresponding device is simultaneously suppressed. Consequently, the target device achieves a high PCE of 11.13% with an open-circuit voltage (VOC) of 1.325 V for hole-free, carbon-based CsPbIBr2 PSCs and 14.56% with a VOC of 1.308 V for CsPbI2Br PSCs. Furthermore, because of the increased ion migration energy, the detrimental phase segregation in this mixed-halide perovskite is weakened, delivering excellent long-term stability for the unencapsulated device in ambient conditions over 70 days with a 96% retention rate of initial efficiency.

A Semisynthesis Platform for the Efficient Production and Exploration of Didemnin-Based Drugs.

Plitidepsin (or dehydrodidemnin B), an approved anticancer drug, belongs to the didemnin family of cyclic depsipeptides, which are found in limited quantities in marine tunicate extracts. Herein, we introduce a new approach that integrates microbial and chemical synthesis to generate plitidepsin and its analogues. We screened a Tistrella strain library to identify a potent didemnin B producer, and then introduced a second copy of the didemnin biosynthetic gene cluster into its genome, resulting in a didemnin B titer of approximately 75 mg/L. Next, we developed two straightforward chemical strategies to convert didemnin B into plitidepsin, one of which involved a one-step synthetic route giving over 90 % overall yield. Furthermore, we synthesized 13 new didemnin derivatives and three didemnin probes, enabling research into structure-activity relationships and interactions between didemnin and proteins. Our study highlights the synergistic potential of biosynthesis and chemical synthesis in overcoming the challenge of producing complex natural products sustainably and at scale.

Nitric Oxide-Releasing Porous Coating with Antibacterial Activity and Blood Compatibility.

Nitric oxide (NO)-releasing coating is promising to enhance the biocompatibility of medical devices. In this study, polyurethane (PU) and S-nitrosated keratin (KSNO) were dissolved with dimethyl sulfoxide (DMSO) and tetrahydrofuran (THF) to prepare a coating solution. This solution is facile to form a porous coating on various substrates based on solvent-evaporation-induced phase separation (SEIPS). The coating could continuously release NO up to 200 h in the presence of ascorbic acid (Asc). In addition, the coating could accelerate endothelialization by promoting the viability of human umbilical vein endothelial cells (HUVECs) while inhibiting the proliferation of human umbilical artery smooth muscle cells (HUASMCs). Furthermore, the coating had good antibacterial activity and blood compatibility. Taken together, this universal coating provides wider potential applications in the field of cardiovascular implants.

Efficacy and Safety of a Pharmaco-Invasive Strategy Using Half-Dose Recombinant Human Prourokinase in Patients with ST-Segment Elevation Myocardial Infarction During Hospitalization.

This study investigated the efficacy and safety of pharmaco-invasive strategy with half-dose recombinant human prourokinase (PHDP) during hospitalization for patients with ST-segment elevation myocardial infarction (STEMI) to provide references for the treatment of STEMI. Patients with STEMI who fulfilled the inclusion and exclusion criteria and attended Chengde Central Hospital, Hebei Province, China, between September 3, 2019, and December 28, 2021, were included in this study. The experimental group received PHDP and the control group underwent primary percutaneous coronary intervention (PPCI). This study enrolled 150 patients with STEMI, 75 in the experimental group and 75 in the control group. Coronary angiography revealed successful thrombolysis in 64 (85.33%) patients. Compared with the control group, the experimental group had shorter first medical contact-reperfusion time (P < 0.001), less slow flow/no-reflow (P < 0.001), and a lower utilization rate of Tirofiban (P < 0.001). Validity endpoints: no statistically significant differences between the two groups. Safety endpoints: no statistically significant differences between bleeding and major adverse cardiovascular and cerebrovascular events (MACCEs), but the experimental group was more prone to arrhythmias (P = 0.040), particularly premature ventricular beats (PVB) (P = 0.008). In conclusion, the efficacy and safety of PHDP in the treatment of patients with STEMI were positive. Complete epicardial and myocardial reperfusion rates, risk for bleeding during hospitalization, and incidence of MACCEs were similar to those of the PPCI strategy. Although the PHDP group has a higher incidence of PVB, it does not increase the incidence of malignant arrhythmia. This study aimed to provide a new therapeutic strategy for the treatment of STEMI in hospitals without adequate PPCI resources condition.

Machine Learning Modeling for Spatial-Temporal Prediction of Geohazard.

Geohazards, such as landslides, rock avalanches, debris flow, ground fissures, and ground subsidence, pose significant threats to people's lives and property [...].

Neuroprotective Effects of Leptin on the APP/PS1 Alzheimer's Disease Mouse Model: Role of Microglial and Neuroinflammation.

Background: Microglia are closely linked to Alzheimer's disease (AD) many years ago; however, the pathological mechanisms of AD remain unclear. The purpose of this study was to determine whether leptin affected microglia in the hippocampus of young and aged male APP/PS1 mice. Objective: In a transgenic model of AD, we investigated the association between intraperitoneal injection of leptin and microglia. Methods: We intraperitoneal injection of leptin (1mg/kg) every day for one week and analyzed inflammatory markers in microglia in the hippocampus of adult (6 months) and aged (12 months) APP/PS1 mice. Results: In all leptin treatment group, the brain Aß levels were decrease. We found increased levels of IL-1ß, IL-6 and microglial activation in the hippocampus of adult mice. Using aged mice as an experimental model for chronic neuroinflammation and leptin resistance, the number of Iba-1+ microglia and the levels of IL-1ß/IL-6 in the hippocampus were greatly increased as compared to the adult. But between the leptin treatment and un-treatment, there were no difference. Conclusion: Leptin signaling would regulate the activation of microglia and the release of inflammatory factors, but it is not the only underlying mechanism in the neuroprotective effects of AD pathogenesis.

Charge transfer doping of graphene oxide with nickel oxide nanoparticles for stable and efficient carbon-based, all-inorganic CsPbBr3 perovskite solar cells.

All-inorganic CsPbBr3 perovskite solar cells have received growing attention in the photovoltaic field due to their high stability, low cost, and simple preparation processes. However, the high-density defects in perovskite films and the large energy differences at interfaces have been the main challenges for achieving high power conversion efficiency and good stability. In this work, nickel oxide (NiOx) decorated graphene oxide (GO) is used as a hole collector at the perovskite/carbon interface for a carbon-based CsPbBr3 perovskite solar cell. The crystallinity of the CsPbBr3 perovskite layer and the hole extraction ability are markedly enhanced because of the p-type charge transfer doping of GO from oxygenic groups to NiOx. Finally, the all-inorganic CsPbBr3 perovskite solar cell achieves a power conversion efficiency of 8.59%. More importantly, the best solar cell free of encapsulation retains 94.2% of its initial efficiency in an air environment over 21 days.

Engineering Amorphous-Crystallized Interface of ZrNx Barriers for Stable Inverted Perovskite Solar Cells.

It is challenging to achieve long-term stability of perovskite solar cells due to the corrosion and diffusion of metal electrodes. Integration of compact barriers into devices has been recognized as an effective strategy to protect the perovskite absorber and electrode. However, the difficulty is to construct a thin layer of a few nanometers that can delay ion migration and impede chemical reactions simultaneously, in which the delicate microstructure design of a stable material plays an important role. Herein, ZrNx barrier films with high amorphization are introduced in p-i-n perovskite solar cells. To quantify the amorphous-crystalline (a-c) density, pattern recognition techniques are employed. It is found the decreasing a-c interface in an amorphous film leads to dense atom arrangement and uniform distribution of chemical potential, which retards the interdiffusion at the interface between ions and metal atoms and protect the electrodes from corrosion. The resultant solar cells exhibit improved operational stability, which retains 88% of initial efficiency after continuous maximum power point tracking under 1-Sun illumination at room temperature (25 °C) for 1500 h.

A trifunctional polyethylene oxide buffer layer for stable and efficient all-inorganic CsPbBr3 perovskite solar cells.

Carbon-based all-inorganic perovskite solar cells have attracted growing interest owing to their simple fabrication process, low cost, and high stability in air. On account of the large interfacial energy barriers and polycrystalline features of perovskite films, the carrier interface recombination and inherent defects in the perovskite layer are still great challenges in further increasing the power conversion efficiency and stability of carbon-based PSCs. We present here a trifunctional polyethylene oxide buffer layer at the perovskite/carbon interface to promote the PCE and stability of carbon-based all-inorganic CsPbBr3 PSCs: (i) the PEO layer increases the crystallinity of inorganic CsPbBr3 grains for low defect state density; (ii) the oxygenic groups in PEO chains passivate the defects on the perovskite surface; and (iii) the long hydrophobic alkyl chains improve the stability in moisture. The best encapsulated PSC achieves a PCE of 8.84% and maintains 84.8% of its initial efficiency in air with 80% RH over 30 days.

A photovoltaic-hydrovoltaic-coupled carbon-based, all-inorganic CsPbBr3 perovskite solar cell.

A photovoltaic-hydrovoltaic-coupled carbon-based, all-inorganic Cs0.91Rb0.09PbBr3 perovskite solar cell achieved a peak power conversion efficiency of 9.40% under one sun illumination and a maximum voltage of 0.39 V and current of 1.40 µA in a flowing vapor atmosphere.

Inhibited Crack Development by Compressive Strain in Perovskite Solar Cells with Improved Mechanical Stability.

Metal halide perovskites are promising as next-generation photovoltaic materials, but stability issues are still a huge obstacle to their commercialization. Here, the formation and evolution of cracks in perovskite films during thermal cycling, which affect their mechanical stability, are investigated. Compressive strain is employed to suppress cracks and delamination by in situ formed polymers with low elastic modulus during crystal growth. The resultant devices pass the thermal-cycling qualification (IEC61215:2016), retaining 95% of the initial power conversion efficiency (PCE) and compressive strain after 230 cycles. Meanwhile, the p-i-n devices deliver PCEs of 23.91% (0.0805 cm2 ) and 23.27% (1 cm2 ). The findings shed light on strain engineering with respect to their evolution, which enables mechanically stable perovskite solar cells.