Reactive Oxygen Species-Responsive Delivery of a Notch Inhibitor to Alleviate Nonalcoholic Steatohepatitis by Inhibiting Hepatic de Novo Lipogenesis and Inflammation.

With the increased prevalence of nonalcoholic steatohepatitis (NASH) in the world, effective pharmacotherapy in clinical practice is still lacking. Previous studies have shown that dibenzazepine (DBZ), a Notch inhibitor, could alleviate NASH development in a mouse model. However, low bioavailability, poor water solubility, and extrahepatic side effects restrict its clinical application. To overcome these barriers, we developed a reactive oxygen species (ROS)-sensitive nanoparticle based on the conjugation of bilirubin to poly(ethylene glycol) (PEG) chains, taking into account the overaccumulation of hepatic ROS in the pathologic state of nonalcoholic steatohepatitis (NASH). The PEGylated bilirubin can self-assemble into nanoparticles in an aqueous solution and encapsulate insoluble DBZ into its hydrophobic cavity. DBZ nanoparticles (DBZ Nps) had good stability, rapidly released DBZ in response to H2O2, and effectively scavenged intracellular ROS of hepatocytes. After systemic administration, DBZ Nps could accumulate in the liver of the NASH mice, extend persistence in circulation, and improve the bioavailability of DBZ. Furthermore, DBZ Nps significantly improved glucose intolerance, relieved hepatic lipid accumulation and inflammation, and ameliorated NASH-induced liver fibrosis. Additionally, DBZ Nps had no significant extrahepatic side effects. Taken together, our results highlight the potential of the ROS-sensitive DBZ nanoparticle as a promising therapeutic strategy for NASH.

Nonlinear association between proteinuria levels and the risk of cardiovascular disease events and all-cause mortality among chronic kidney disease patients.

BACKGROUND: The association between proteinuria levels and cardiovascular disease (CVD) development and all-cause mortality in chronic kidney disease (CKD) patients remains controversial. METHODS: In this investigation, we conducted a retrospective analysis involving 1138 patients who were registered in the CKD-Research of Outcomes in Treatment and Epidemiology (ROUTE) study. The primary outcome of this study was the composite of cardiovascular events or all-cause death. Cox proportional hazards regression, smooth curve fitting, piecewise linear regression, and subgroup analyses were used. RESULTS: The mean age of the included individuals was 67.3 ± 13.6 years old. Adjusted hazard ratios (HRs) for UPCR in middle and high groups, compared to the low group, were 1.93 (95% CI: 1.28-2.91) and 4.12 (95% CI: 2.87-5.92), respectively, after multivariable adjustment. Further adjustments maintained significant associations; HRs for middle and high groups were 1.71 (95% CI: 1.12-2.61) and 3.07 (95% CI: 2.08-4.54). A nonlinear UPCR-primary outcome relationship was observed, with an inflection point at 3.93 g/gCr. CONCLUSION: Among non-dialyzed patients with stage G2-G5 CKD, a nonlinear association between UPCR and the primary outcome was observed. A higher UPCR (when UPCR < 3.93 g/gCr) was an independent predictor of the primary outcome. Importantly, our study predates SGLT2 inhibitor use, showcasing outcomes achievable without these medications. Future research considerations will involve factors like SGLT-2 inhibitor utilization.

Electron Density Changes and Ultrafast Carrier Dynamics of the Antiferromagnetic Semiconductor MnPS3 through Magnetic Phase Transition.

Studying ultrafast dynamics provides us with a way to modify materials from the timescale of particle interaction, and the related research on antiferromagnetic semiconductors is still inadequate. Based on the electron density reconstruction, we achieve the visualization of magnetic interactions of bulk antiferromagnetic MnPS3 in the ground state, reveal the role of two atomic site occupations of S atoms in different magnetic phase transitions, and provide the theoretical and experimental support for modifying magnetic properties by selectively replacing the S atom. The ultrafast carrier dynamics can provide information from the excited state to the ground state. Based on time-resolved transmittance measurements, ultrafast carrier dynamics of MnPS3 are reported. The phonon-assisted gap transition driven by the electronic structure is characterized. The coupling relationship among electrons, spin, and phonons is established. Furthermore, the spin orientations within different phases are confirmed.

Detection of hypokalemia disorder and its relation with hypercalcemia in blood serum using LIBS technique for patients of colorectal cancer grade I and grade II.

Cancer continues to be the most dangerous disease around the world; it causes electrolyte imbalance as well as metabolic changes. There is a complicated relationship between electrolyte disorder and cancer. Cancer patients commonly pass with abnormalities in serum electrolyte levels such as hypokalemia, hyperkalemia, hyponatremia, and hypercalcemia. So, these electrolyte imbalances indicate the existence of paraneoplastic processes and help come to a more informed prognosis. Hypokalemia is defined as a serum potassium concentration below 3.5 mmol/L and it is the second common electrolyte imbalance seen in patients with malignant diseases. In this paper, the contribution of serum potassium concentration to tumor progression was studied by applying a promising and non-invasive technique called laser-induced breakdown spectroscopy (LIBS). It was found that there is a correlation between hypokalemia and the colorectal cancer problem. Also, significant serum potassium concentration differences were detected among two different stages of the same cancer and also between two groups of the same stage of a cancer held in common but one of them suffers from hypercalcemia. In addition, the optimum conditions of LIBS setup were arranged such that it will be suitable to work with serum samples on glass substrate.

Study on Spectral Selective Manipulation Characteristics of Surface Multilevel Micro-Nano Structures by FDTD Simulation.

The optical filter based on the micro-nano structure on the material surface is an important optical device, which is widely used in many fields. The filter is fabricated on the substrate with different shapes and sizes of micro-nano array structure, and the wavelength selectivity is realized by adjusting the processing parameters. In this paper, the finite-difference time-domain (FDTD) method is used to simulate the spectral properties of periodic array structures on the Au surface, and the spectral response characteristics of different surface structural parameters to the incident light are obtained. The simulation results show that the periodic pore array has a directional modulation function on the reflectivity and transmittance of the material surface. In the same circular aperture array structure, the wavelength selection ability is proportional to the interval distance of the array period, but the transmission peak linewidth decreases with the increase of the interval distance. The structural spectrum of the cylindrical array is closely related to the structural period. The period of the array structure increases in proportion, the center wavelengths of the reflection and transmission peak of the spectrum are red-shifted. When the height of the array structure increases proportionally, the positions of the center wavelengths of the reflection and transmission peak remain almost unchanged. When the period of the array structure increases, the center wavelength of the reflection and transmission peaks appear red-shifted, and the line width is also narrowed. For the periodic ring array structure, as the inner diameter increases, the reflection peak is significantly red-shifted, and the smaller the ring width, the faster the red-shift of the reflection peak with the wavelength. By controlling the ratio of inner diameter-to-outer diameter, the spectral characteristics of the structured surface can be effectively controlled. These simulation results provide a basis for the preparation of optical filters in the future and a new idea for the study of micro-nano characteristic structures on the surface of materials.

Discovery of isoliquiritigenin analogues that reverse acute hepatitis by inhibiting macrophage polarization.

Screening a natural product library of 850 compounds yield isoliquiritigenin as an effective anti-inflammatory agent by inhibiting the production of pro-inflammatory NO induced by Pam3CSK4, while its activity accompanied by toxicity. Further studies obtained the optimized isoliquiritigenin derivative SMU-B14, which can inhibit Pam3CSK4 triggered toll-like receptor 2 (TLR2) signaling with low toxicity and high potency. Preliminary mechanism studies indicated that SMU-B14 worked through TLR2/MyD88, phosphorylation of IKKα/ß, leading to the reduce degradation of NF-κB related IKBα and p65 complex, then inhibited the production of inflammatory cytokines, such as TNF-α, IL-6, IL-1ß both in human and murine cell lines. Subsequent polarization experiments showed SMU-B14 significant reversed the polarization of M1 phenotype primary macrophage activated by Pam3CSK4in vitro, and reduced the infiltration of neutrophil and polarization of M1-type macrophage, decreased serum alanine transaminase (ALT), as a result protected liver from being injured in vivo. In summary, we obtained an optimized lead compound SMU-B14 and found it functionally blocked TLR2/MyD88/NF-κB signaling pathway to down-regulate the production of inflammatory cytokines resulted significant liver protection property.

Panax notoginseng Preparations for Unstable Angina Pectoris: A Systematic Review and Meta-Analysis.

This paper assessed the evidence of Panax notoginseng preparations in patients suffering from UAP using meta-analysis and systematic review methods. Methods were according to the Cochrane Handbook and analysed using Revman 5.3. A search of PubMed, Cochrane Library, Embase, MEDLINE, Chinese national knowledge infrastructure (CNKI), Vip information database, Wanfang data and Chinese Biomedical Literature Database (SinoMed) was conducted to identify randomized controlled trials (RCTs) of P. notoginseng preparations on UAP regardless of blinding, sex and language. The outcomes include all-cause mortality, cardiac mortality, cardiovascular events, UAP symptoms, improvement of electrocardiogram and adverse events. Eighteen RCTs including 1828 patients were identified. The level of reporting is generally poor. Among 18 studies, 16 studies were prescribed P. notoginseng injections, and two studies were oral P. notoginseng preparations. Reduction of cardiovascular events (RR:0.35;95% CI:0.13 to 0.94), alleviation of angina pectoris symptoms (RR:1.23;95% CI 1.18 to 1.29), improvement of ECG (RR:1.22;95% CI 1.15 to 1.28) and reduced frequency of angina pectoris (MD:-1.48; 95% CI -2.49 to -0.48) were observed. Cardiac mortality and duration of angina pectoris were not statistically significant. Panax notoginseng is beneficial to UAP patients; the results of these reviews may have important implications to clinical work. Copyright © 2017 John Wiley & Sons, Ltd.

Subwavelength topological structures resulting from surface two-plasmon resonance by femtosecond laser exposure solid surface.

We present that surface two-plasmon resonance (STPR) in electron plasma sheet produced by a femtosecond laser irradiating a solid surface is the self-formation mechanism of periodic subwavelength ripple structures. Peaks of overdense electrons, formed by resonant two-plasmon wave mode, pull bound ions out of the metal surface. Thus, the wave pattern of STPR is "carved" on the surface by Coulomb ablation (removal) due to periodic distributed strong electrostatic field produced by charge separation. To confirm the STPR model, we have performed analogical carving experiments by two femtosecond laser beams with perpendicular polarizations and time delay. The results explicitly show that two wave patterns of STPR generated by each beam are independently created in the pulse exposure area of a target surface, which is like the traditional "layer-carving" technique by comparison with the structured topological features. The time-scale of ablation dynamics and the electron temperature in ultrafast interaction are also verified by a time-resolved spectroscopy experiment and numerical simulation, respectively. The present model can self-consistently explain the formation of subwavelength ripple structures even with spatial periods shorter than half of the laser wavelength, shedding light on the understanding of ultrafast laser-solid interaction.

Improved moth-flame algorithm based on cat chaotic and dynamic cosine factor.

The moth-flame algorithm shows some shortcomings in solving the complex problem of optimization, such as insufficient population diversity and unbalanced search ability. In this paper, an IMFO (Improved Moth-Flame Optimization) algorithm is proposed to be applied in solving the optimization problem of function. First, cat chaotic mapping is used to generate the initial position of moth to improve the population diversity. Second, cosine inertia weight is introduced to balance the global and local search abilities of the algorithm. Third, the memory information in the particle swarm algorithm is introduced into the iterative process of the algorithm to speed up the convergence of the population. Finally, Gaussian mutation strategy is used in the current optimal solution to avoid the algorithm from falling into the local optimum. Simulation experiments are conducted on 11 benchmark test functions, compared with other improved MFO (Moth-Flame Optimization) algorithms and classical optimization algorithms. The results show that the IMFO has higher accuracy and stability in solving the above-mentioned test functions. The proposed algorithm is experimented and verified by optimizing the KELM (Kernel Extreme Learning Machine) in an engineering example and exhibits a better optimization performance.

Defining the threshold: triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio's non-linear impact on tubular atrophy in primary membranous nephropathy.

Background: Hyperlipidemia is common in primary membranous nephropathy (PMN) patients, and tubular atrophy (TA) is an unfavorable prognostic factor. However, the correlation between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and TA is controversial. Therefore, our study aimed to investigate the association between the TG/HDL-C ratio and TA in PMN patients. Methods: We conducted a cross-sectional study and collected data from 363 PMN patients at Shenzhen Second People's Hospital from January 2008 to April 2023. The primary objective was to evaluate the independent correlation between the TG/HDL-C ratio and TA using binary logistic regression model. We used a generalized additive model along with smooth curve fitting and multiple sensitivity analyses to explore the relationship between these variables. Additionally, subgroup analyses were conducted to delve deeper into the results. Results: Of the 363 PMN patients, 75 had TA (20.66%). The study population had a mean age of 46.598 ± 14.462 years, with 217 (59.78%) being male. After adjusting for sex, age, BMI, hypertension, history of diabetes, smoking, alcohol consumption, UPRO, eGFR, HB, FPG, and ALB, we found that the TG/HDL-C ratio was an independent risk factor for TA in PMN patients (OR=1.29, 95% CI: 1.04, 1.61, P=0.0213). A non-linear correlation was observed between the TG/HDL-C ratio and TA, with an inflection point at 4.25. The odds ratios (OR) on the left and right sides of this inflection point were 1.56 (95% CI: 1.17, 2.07) and 0.25 (95% CI: 0.04, 1.54), respectively. Sensitivity analysis confirmed these results. Subgroup analysis showed a consistent association between the TG/HDL-C ratio and TA, implying that factors such as gender, BMI, age, UPRO, ALB, hypertension and severe nephrotic syndrome had negligible effects on the link between the TG/HDL-C ratio and TA. Conclusion: Our study demonstrates a non-linear positive correlation between the TG/HDL-C ratio and the risk of TA in PMN patients, independent of other factors. Specifically, the association is more pronounced when the ratio falls below 4.25. Based on our findings, it would be advisable to decrease the TG/HDL-C ratio below the inflection point in PMN patients as part of treatment strategies.

Silver dendrite metasurface SERS substrates prepared by photoreduction method for perfluorooctanoic acid detection.

Perfluorooctanoic acid (PFOA), a novel organic pollutant, has been shown to be toxic, persistent, bioaccumulative, long-range transportable, and globally prevalent. This article is based on surface enhanced Raman scattering (SERS) spectroscopy analysis technology. The monolayer of SiO2 was prepared by chemical reduction etching self-assembly method and silver dendrites were grown on it, thus forming the SERS substrate with silver dendrite Metasurface structure with Raman detection enhancement factor up to 2.32 × 105. The prepared silver dendrite Metasurface SERS substrate was applied to the qualitative and quantitative detection of PFOA, with a quantitative detection limit of 15.89 ppb. The results of this paper provide a new, simple, and quick method for the detection of PFOA in the environment.

Anisotropic carrier dynamics and laser-fabricated luminescent patterns on oriented single-crystal perovskite wafers.

Perovskite materials and their applications in optoelectronics have attracted intensive attentions in recent years. However, in-depth understanding about their anisotropic behavior in ultrafast carrier dynamics is still lacking. Here we explore the ultrafast dynamical evolution of photo-excited carriers and photoluminescence based on differently-oriented MAPbBr3 wafers. The distinct in-plane polarization of carrier relaxation dynamics of the (100), (110) and (111) wafers and their out-of-plane anisotropy in a picosecond time scale were found by femtosecond time- and polarization-resolved transient transmission measurements, indicating the relaxation process dominated by optical/acoustic phonon interaction is related to photoinduced transient structure rearrangements. Femtosecond laser two-photon fabricated patterns exhibit three orders of magnitude enhancement of emission due to the formation of tentacle-like microstructures. Such a ultrafast dynamic study carried on differently-oriented crystal wafers is believed to provide a deep insight about the photophysical process of perovskites and to be helpful for developing polarization-sensitive and ultrafast-response optoelectronic devices.

A modified rate equation for the propagation of a femtosecond laser pulse in field-ionizing medium.

A recombination rate of electron-ion in the strong-field atomic process is phenomenologically introduced into the ionization rate equation, and therefrom an ionization and recombination rates equation (IRRE) is obtained. By using the extended IRRE, the propagation equation of an intense femtosecond laser pulse in the gaseous medium is re-derived. Some new physical behaviors and characteristics caused by the introduced recombination rate are discussed in detail.

Does the perception of smart governance enhance commercial investments? Evidence from Beijing, Shanghai, Guangzhou, and Hangzhou.

This study explores how the perception of specific aspects of smart governance affects the business environment as to attract investment. To this end, we used a survey design and collected data from Beijing, Shanghai, Guangzhou, and Hangzhou. A total of 500 responses from different industries and companies were obtained and then empirically analyzed using ridge regression and intermediary effect models. We found that the perception of smart governance enhances investment due to strong governance and abundant business opportunities. Natural sustainability attracts investment directly because, when cities become smart, they tend to improve their sustainability and attract talent and capital inflows. This external participation has a direct impact on enterprise investment because it creates more business opportunities. An improved social credit system represents the comprehensive progress of the business environment and positively mediates smart governance and investment. This is the first study to combine the key elements of smart governance, the development stage of smart governance, and various dimensions of the business environment to analyze the influence of smart governance perceptions on commercial investments.

α-tocopherol pretreatment alleviates cerebral ischemia-reperfusion injury in rats.

α-tocopherol showed antioxidant, anti-inflammatory and anti-apoptotic abilities in rat brain tissue, thus alleviating cerebral ischemia-reperfusion injury-induced nerve damage.

Does a smart business environment promote corporate investment? a case study of Hangzhou.

As a result of business environment reforms in China's Hangzou, the cost of business has reduced, the confidence of Hangzhou enterprises has survived the COVID-19 outbreak, and foreign investment continues to increase. Nevertheless, Hangzhou's business environment has shortcomings, such as insufficient technology, talent, and intelligent infrastructure. Two unresolved questions persist: (i) Has the smart business environment stimulated corporate investment by reducing system costs and boosting corporate confidence? (ii) How do the commercial climate's shortcomings impact the relationship between the intelligent business environment and business costs/confidence? We examined the impact of a local smart business environment on the corporate investment scale in Hangzhou using factor analysis, cluster analysis, linear regression, and path analyses of data from 297 firm managers. Smart governance improved public administration, financing, and rule of law. The business environment promoted investment by increasing business confidence and decreasing institutional costs. Weak intelligent property protection and legal fairness hindered the positive influence of smart governance on business confidence and system costs. This is the first study combining business environment, smart city, and smart governance concepts to analyze the influence of local smart business environments on business confidence, institutional costs, and investment. Our conclusion on the limitation effect of intelligent business environment on enterprise investment attempts to inspire further research on the intersection of business environments and smart cities. The law of intelligent business environment attracting investment obtained in the context of China, the largest developing country with diversified economic development, is of great significance for other developing countries. Countries can attract investment and promote economic development through intelligent governance. Developing countries should construct smart service platforms, coordinate supervision of public credit, reduce financing constraint, construct a government under the rule of law, improve the quality of land management, and protect intellectual property rights.

Association of the serum albumin level with prognosis in chronic kidney disease patients.

PURPOSE: Chronic kidney disease (CKD) is an important contributor to the overall morbidity and mortality due to noncommunicable diseases. We investigated the relationship between serum albumin and the clinical prognosis in patients with stage G2-G5 CKD who were not undergoing dialysis. METHODS: This was a post hoc analysis of 1138 patients enrolled from 2010 to 2011 in the Chronic Kidney Disease Research of Outcomes in Treatment and Epidemiology (CKD-ROUTE) study. The primary endpoints were CKD progression, cardiovascular disease (CVD) development, and all-cause mortality. Cox proportional hazards models were used. RESULTS: During a median follow-up time of 35 months, the number of patients who experienced CKD progression, CVD development, and all-cause mortality was 278 (24.7%), 116 (10.3%), and 78 (6.9%), respectively. In multivariable-adjusted Cox proportional hazards models, the adjusted hazard ratios (HRs) for CKD progression, CVD development, and all-cause mortality in patients with the highest quartile of serum albumin concentrations compared to those with the lowest quartile of serum albumin concentrations were 0.13 (P < 0.0001), 0.29 (P = 0.0002), and 0.27 (P = 0.0009), respectively, in the model adjusted for demographic factors, hypertension, diabetes, and a history of CVD. After further adjustment for the estimated glomerular filtration rate (eGFR), urinary protein/creatinine ratio (UPCR), and systolic blood pressure (SBP), the results remained significant (HR for CKD progression 0.37, P < 0.0001; HR for CVD development 0.41, P = 0.0120; HR for all-cause mortality 0.37, P = 0.0158). CONCLUSION: Serum albumin levels were inversely associated with the risks of CKD progression, CVD development, and all-cause mortality among patients with stage G2-G5 CKD who were not undergoing dialysis.

Evaluating Atherosclerosis of the Abdominal Aorta in Rabbits Using 2-D Strain Imaging.

After establishment of an animal model of atherosclerosis, speckle tracking imaging was performed to analyze the correlation between ultrasound characteristics and pathological manifestations. Rabbits were divided into the normal control (NC) and atherosclerosis (AS) groups. Rabbits in the AS group were subjected to ultrasound-guided balloon injury of the abdominal aorta and fed a high-fat diet for 16 wk. Rabbits in the NC group were fed a normal diet for the same period. After 16 wk, all animals underwent serological tests, ultrasound and speckle tracking circumferential strain analysis. In the AS group, 28 hypo-echoic plaques had formed. The circumferential strain of six segments at the short axis of plaques in the AS group was lower than that in the NC group (p < 0.001), and global circumferential strain (GCS) in the AS group was significantly reduced compared with the NC group (p < 0.001). In the AS group, the area ratio of type I to type III collagen fibers was smaller than that in the NC group. The GCS of atherosclerotic plaques was positively correlated with the area ratio of type I to type III collagen fibers in plaques (r = 0.7181, p < 0.001). In conclusion, there is a significant positive correlation between the decreased circumferential strain and the decreased area ratio of type I to type III collagen fibers in hypo-echoic plaques.

Development and validation of mathematical nomogram for predicting the risk of poor sleep quality among medical students.

Background: Despite the increasing prevalence of poor sleep quality among medical students, only few studies have identified the factors associated with it sing methods from epidemiological surveys. Predicting poor sleep quality is critical for ensuring medical Students' good physical and mental health. The aim of this study was to develop a comprehensive visual predictive nomogram for predicting the risk of poor sleep quality in medical students. Methods: We investigated medical Students' association with poor sleep quality at JiTang College of North China University of Science and Technology through a cross-sectional study. A total of 5,140 medical students were randomized into a training cohort (75%) and a validation cohort (25%). Univariate and multivariate logistic regression models were used to explore the factors associated with poor sleep quality. A nomogram was constructed to predict the individual risk of poor sleep quality among the medical students studied. Results: 31.9% of medical students in the study reported poor sleep quality. We performed multivariate logistic analysis and obtained the final model, which confirmed the risk and protective factors of poor sleep quality (p < 0.05). Protective factors included the absence of physical discomfort (OR = 0.638, 95% CI: 0.546-0.745). Risk factors included current drinking (OR = 0.638, 95% CI: 0.546∼0.745), heavy study stress (OR = 2.753, 95% CI: 1.456∼5.631), very heavy study stress (OR = 3.182, 95% CI: 1.606∼6.760), depressive symptoms (OR = 4.305, 95% CI: 3.581∼5.180), and anxiety symptoms (OR = 1.808, 95% CI: 1.497∼2.183). The area under the ROC curve for the training set is 0.776 and the area under the ROC curve for the validation set is 0.770, which indicates that our model has good stability and prediction accuracy. Decision curve analysis and calibration curves demonstrate the clinical usefulness of the predictive nomograms. Conclusion: Our nomogram helps predict the risk of poor sleep quality among medical students. The nomogram used includes the five factors of drinking, study stress, recent physical discomfort, depressive symptoms, and anxiety symptoms. The model has good performance and can be used for further research on and the management of the sleep quality of medical students.