Inhibition of autophagy induced by tetrandrine promotes the accumulation of reactive oxygen species and sensitizes efficacy of tetrandrine in pancreatic cancer.

Pancreatic cancer, characterized by its poor prognosis, exhibits a marked resistance to conventional chemotherapy and immunotherapy, underscoring the urgent need for more effective treatment modalities. In light of this, the present study is designed to assess the potential antineoplastic efficacy of a combined regimen involving tetrandrine, a plant-derived alkaloid, and autophagy inhibitors in the context of pancreatic cancer. Electron microscopy and immunoblots showed that tetrandrine promoted the formation of autophagosomes and the upregulation of LC3II and the downregulation of p62 expression, indicating that tetrandrine induced autophagy in pancreatic cancer cells. Western blot revealed that tetrandrine inhibited the phosphorylation of AKT and mTOR, as well as the expression of Bcl-2, while upregulating Beclin-1 expression. Moreover, tetrandrine promoted the transcription and protein expression of ATG7. Following the combination of autophagy inhibitors and tetrandrine, the apoptotic rate and cell death significantly increased in pancreatic cancer cells. Consistent results were obtained when ATG7 was silenced. Additionally, tetrandrine induced the generation of ROS, which was involved in the activation of autophagy and apoptosis. Further investigation revealed that upon autophagy inhibition, ROS accumulated in pancreatic cancer cells, resulting in decreased mitochondrial membrane potential and further induction of apoptosis. The results of treating subcutaneous xenograft tumors with a combination of tetrandrine and chloroquine validated that autophagy inhibition enhances the toxicity of tetrandrine against pancreatic cancer in vivo. Altogether, our study demonstrates that tetrandrine induces cytoprotective autophagy in pancreatic cancer cells. Inhibiting tetrandrine-induced autophagy promotes the accumulation of ROS and enhances its toxicity against pancreatic cancer.

A Straightforward Solvent-Pair-Enabled Multicomponent Coassembly Approach toward Noble-Metal-Nanoparticle-Decorated Mesoporous Tungsten Oxide for Trace Ammonia Sensing.

The straightforward synthesis of noble-metal-nanoparticle-decorated ordered mesoporous transition metal oxides remains a great challenge due to the difficulty of balancing the interactions between precursors and templates. Herein, a solvent-pair-enabled multicomponent coassembly (SPEMC) strategy is developed for straightforward synthesis of noble-metal-nanoparticle-decorated nitrogen-doped ordered mesoporous tungsten oxide (abbreviated as NM/N-mWO3, NM = Pt, Rh, Pd). The amphiphilic poly(ethylene oxide)-block-polystyrene (PEO-b-PS) copolymers coassemble with ammonium metatungstate (AMT) clusters and different kinds of hydrophilic noble metal precursors without phase separation. SPEMC synthesis requires no direct interaction between PEO-b-PS and AMT, thus the assembly equilibriums between noble metal precursors and PEO-b-PS can be readily controlled. The obtained NM/N-mWO3 nanocomposites possess ordered mesopores, abundant oxygen vacancies, and metal-metal oxide interfaces. As a result, the Pt/N-mWO3 sensors exhibit superior ammonia sensing performances with high sensitivity, an ultralow limit of detection (51.2 ppb), good selectivity, and long-term stability. Spectroscopic analysis reveals that ammonia is oxidized stepwise to NO, NO2 -, and NO3 - during the sensing process. Moreover, a portable wireless module based on Pt/N-mWO3 sensor can recognize ppm-level concentration of ammonia, which lays a solid foundation for its application in various fields.

A bibliometric analysis of endoplasmic reticulum stress and atherosclerosis.

The mechanisms underlying the occurrence and development of atherosclerosis (AS) are diverse, among which endoplasmic reticulum stress (ERS) is an important mechanism that should not be overlooked. However, up to now, there has been no bibliometric study on the relationship between ERS and AS. To understand the research progress in ERS and AS, this paper conducted a statistical analysis of publications in this field using bibliometrics. A total of 1,035 records were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, and the R package "bibliometric" were used to analyze the spatiotemporal distribution, countries, authors, institutions, journals, references, and keywords of the literature, and to present the basic information of this field through visualized maps, as well as determine the collaboration relationships among researchers in this field. This field has gradually developed and stabilized over the past 20 years. The current research hotspots in this field mainly include the relationship between ERS and AS-related cells, the mechanisms by which ERS promotes AS, related diseases, and associated cytokines, etc. Vascular calcification, endothelial dysfunction, NLRP3 inflammasome, and heart failure represent the frontier research in this field and are becoming new research hotspots. It is hoped that this study will provide new insights for research and clinical work in the field of ERS and AS.

Longitudinal Association between Stressful Life Events and Suicidal Ideation in Adults with Major Depression Disorder: The Mediating Effects of Insomnia Symptoms.

Stressful life events (SLEs) and suicidal ideation (SI) are prevalent in persons with major depression disorder (MDD). Less is known about the underlying role of insomnia symptoms in the association between SLEs and SI. This three-wave prospective cohort study sought to investigate the longitudinal association among SLEs, insomnia symptoms, and SI in persons with MDD. The study population included 511 persons with MDD (mean [SD] age, 28.7 [6.7] years; 67.1% were females). Generalized estimated equations (GEEs) were utilized to explore prospective association among exposure of SLEs, insomnia symptoms, and SI. Additionally, a structural equation model (SEM) was employed to estimate the longitudinal mediating effect of insomnia symptoms in the relationship between SLEs and SI. Our study demonstrated that cumulative SLEs were determined to be longitudinally associated with SI in persons with MDD. We further observed that the association between SLEs and SI was significantly mediated by insomnia symptoms. Clinicians assessing persons with MDD, especially those with the history of SLE, could carefully evaluate and promptly treat insomnia symptoms as part of personalized assessment of their depressive illness, thereby achieving early prevention and intervention for suicidal behaviors in persons with MDD.

Compressibility of lime-treated dredged slurry with high water content.

Lime is widely used for soft ground treatment, rendering the compressibility of lime-treated soil a crucial factor in deformation analysis in engineering applications. This study investigated the compressibility of three remoulded lime-treated slurries with high water content in Southeast China. Sixty groups of oedometer tests were conducted on lime-treated soils with an initial water content of 1 to 3 times the liquid limit and lime contents between 1 and 3%. The oedometer test results were discussed to examine the remoulded yield stress σ y ' of lime-treated slurry. Considering the relationships between σ y ' , the void ratio, lime content, and initial water content were preliminarily discussed and quantitatively established. Research on the normalised compression curve of lime-treated soil revealed that for soil samples containing a lime content of 0-%, the normalised compression curve at σ p ' > σ y ' can be represented by a unique line. Furthermore, the log(1 + e) - log σ v ' compression curve of lime-treated slurry at pre-yield state is analysed, and a prediction method for the modified compression index is proposed.

Ultrasensitive enantiomeric barbiturate analysis in body fluids through capillary electrophoresis with large volume sample stacking and ultrasound assisted dispersive liquid liquid microextraction.

A rapid, straightforward, and sensitive approach to quantifying enantiomeric barbiturates in serum was developed by integrating ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) with large-volume sample stacking (LVSS) in capillary electrophoresis (CE). UA-DLLME was employed for sample preparation, and on-column preconcentration by using LVSS with polarity switching was implemented to enhance sensitivity. We thoroughly investigated and optimized various parameters influencing extraction and stacking to achieve optimal detection performance with the highest enrichment efficiencies. Under optimal extraction conditions (injection of a mixed solution containing 40 µL of CHCl3 and 200 µL of tetrahydrofuran into 1 mL of a sample solution at pH 10.0), LVSS was performed using 600 mM Tris-boric acid (pH 9.5) containing 35 mM hydroxypropyl-ß-cyclodextrin and sodium taurodeoxycholate hydrate. A voltage of 20 kV was applied and a preinjection water plug was loaded at a height of 25 cm for 10 s. Subsequently, the sample solution was injected at a height of 25 cm for 480 s, after which a voltage of -20 kV was applied and the sample stacking was initiated. The stacking process was completed when 95 % of the separation current was attained. Under optimized conditions, the contraction folds of the four barbiturate analytes (R, S-Secobarbital, R, S-pentobarbital) were improved by approximately 6400-fold, achieving detection limits of 0.1 ng/mL. The limits of quantification for all analyte enantiomers were 0.5-50 ng/mL, demonstrating good linearity (r > 0.997). Migration times exhibited a relative standard deviation of less than 1.7 %, whereas peak areas for the four analytes exhibited a deviation of 8.7 %. Finally, the established method was effectively applied to the analysis of human serum samples.

Study on the Flow Characteristics of Heavy Oil-Water Two-Phase Flow in the Horizontal Pipeline.

Aiming at the problem of transportation for heavy oil during the middle-later development stages of the Lvda oilfield, based on the self-developed design of a visual circulating flow experimental apparatus for heavy oil-water two-phase flow-the flow regime characteristics and corresponding drag properties of the two-phase flow of Lvda viscous oil, which is simulated by 500# industrial white oil and water in a horizontal pipeline are investigated experimentally. According to the Kelvin-Helmholtz instability theory, the flow pattern transition criteria from stratified flow to annular flow (AF) are proposed. The effects of 0.11-0.90 m/s oil superficial velocities, 0.06-1.49 m/s water superficial velocities, and 0.09-0.93 input water cuts on the drag reduction effect of different flow regimes are analyzed. The experimental results indicated that with the increase of mixing velocity and water volume fraction, stratified flow, AF, oil plug flow, and dispersed oil lump flow are successively observed in the horizontal heavy oil-water two-phase flow, in which AF is the main flow pattern. As the Froude number increases to 4.0, the input water volume fraction does not change any more and remains at about 10% of the total flow rate in the process of converting from stratified flow to AF. The four delivery approaches can archive the reduction of transportation resistance for heavy oil at different degrees, in which the transportation of heavy oil surrounded by a water ring has the best effect of drag reduction. At the optimal working conditions of 0.61 m/s oil superficial velocity, 0.07 m/s water superficial velocity, and 0.10 input water cut, the pressure drop of water annulus conveying for heavy oil is only 1/62.54 of that of separate transport for pure heavy oil under the same oil flow rate.

Portable electrochemical sensing platform based on amidated GO-MOF and PEDOT:PSS for high-efficient detection of ponceau 4R.

A promising electrochemical sensing platform for the detection of ponceau 4R in food has been fabricated based on the carboxylated graphene oxide (GO-COOH), metal-organic framework (MOF) UIO-66-NH2, and poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). To this end GO-COOH was covalently coupled with UIO-66-NH2 through amide reaction, endowing the material (GO-CONH-UIO-66) unique hierarchical pores and high chemical stability and as a result improving the conductivity of MOF and the dispersion of GO. After the addition of PEDOT:PSS into GO-CONH-UIO-66, the continuity and conductivity of the composite (PEDOT:PSS/GO-CONH-UIO-66) have been further enhanced, due to the high conductivity, favorable film-forming, and hydrophilic properties of PEDOT:PSS. Systematic electrochemical experiments confirm that the PEDOT:PSS/GO-CONH-UIO-66/GCE shows satisfactory electrochemical sensing properties towards the detection of ponceau 4R, with a wide linear detection range of 0.01-30 µM, a low limit of detection of 3.33 nM, and a high sensitivity of 0.606 µA µM-1 cm-2. The PEDOT:PSS/GO-CONH-UIO-66 sensing platform was successfully used to detect ponceau 4R in beverage, and the detection results were compared with  high-performance liquid chromatography. As a result, the PEDOT:PSS/GO-CONH-UIO-66 composite shows a promising application prospect for rapid detection of ponceau 4R in food and will play significant role in food safety detection and supervision.

Distinct metabolomic and lipidomic profiles in serum samples of patients with primary sclerosing cholangitis.

Intoduction: Identification of specific metabolome and lipidome profile of patients with primary sclerosing cholangitis (PSC) is crucial for diagnosis, targeted personalized therapy, and more accurate risk stratification. Methods: Nuclear magnetic resonance (NMR) spectroscopy revealed an altered metabolome and lipidome of 33 patients with PSC [24 patients with inflammatory bowel disease (IBD) and 9 patients without IBD] compared with 40 age-, sex-, and body mass index (BMI)-matched healthy controls (HC) as well as 64 patients with IBD and other extraintestinal manifestations (EIM) but without PSC. Results: In particular, higher concentrations of pyruvic acid and several lipoprotein subfractions were measured in PSC in comparison to HC. Of clinical relevance, a specific amino acid and lipid profile was determined in PSC compared with IBD and other EIM. Discussion: These results have the potential to improve diagnosis by differentiating PSC patients from HC and those with IBD and EIM.

Prevalence of Parkinson's disease among adults aged 45 years and older in China: a cross-sectional study based on the China health and retirement longitudinal study.

BACKGROUND: In recent decades, China has experienced a rapid increase in the number of elderly individuals and life expectancy, as well as industrialization, which is associated with an increased prevalence of Parkinson's disease (PD). However, inconsistent results have recently been reported. Therefore, this study aimed to investigate the prevalence and distribution characteristics of PD among individuals aged 45 years and older. METHODS: Using data from the China Health and Retirement Longitudinal Study (CHARLS), we attempted to estimate the prevalence of PD and its distribution characteristics among 19,034 individuals aged 45 years and older residing in 446 communities/villages within 27 provinces/autonomous regions/municipalities in mainland China. Cases were established based on a doctor's previous diagnosis. Crude and age-adjusted prevalence rates were calculated and stratified by age, sex, area of residence, education level, marital status, and geographic region. Logistic regression models were used to identify risk factors associated with PD. RESULTS: We identified 178 patients with PD among 19,034 residents aged 45 years and older. The crude prevalence was 0.94%, and the age-adjusted prevalence was 0.82% for individuals aged 45 years and older. The prevalence of PD increased with age (P < 0.001). No significant differences were found in terms of sex, area of residence, or education level. Stratified by geographic region, the prevalence of PD was greater in North and Northwest China and lower in southern China (p < 0.001). Multiple regression analyses showed that age was a significant risk factor for PD. CONCLUSION: The prevalence of PD increased with age in the Chinese population.

Manipulating 2D Materials through Strain Engineering.

This review explores the growing interest in 2D layered materials, such as graphene, h-BN, transition metal dichalcogenides (TMDs), and black phosphorus (BP), with a specific focus on recent advances in strain engineering. Both experimental and theoretical results are delved into, highlighting the potential of strain to modulate physical properties, thereby enhancing device performance. Various strain engineering methods are summarized, and the impact of strain on the electrical, optical, magnetic, thermal, and valleytronic properties of 2D materials is thoroughly examined. Finally, the review concludes by addressing potential applications and challenges in utilizing strain engineering for functional devices, offering valuable insights for further research and applications in optoelectronics, thermionics, and spintronics.

Maillard Reaction Inspired Microexplosion toward Fast Synthesis of Two-Dimensional Mesoporous Tin Oxides for Efficient Chemiresistive Gas Sensing.

Two-dimensional (2D) mesoporous transition metal oxides are highly desired in various applications, but their fast and low-cost synthesis remains a great challenge. Herein, a Maillard reaction inspired microexplosion approach is applied to rapidly synthesize ultrathin 2D mesoporous tin oxide (mSnO2). During the microexplosion between granular ammonia nitrate with melanoidin at high temperature, the organic species can be carbonized and expanded rapidly due to the instantaneous release of gases, thus producing ultrathin carbonaceous templates with rich functional groups to effectively anchor SnO2 nanoparticles on the surface. The subsequent removal of carbonaceous templates via calcination in air results in the formation of 2D mSnO2 due to the confinement effect of the templates. Pd nanoparticles are controllably deposited on the surface of 2D mSnO2 via in situ reduction, forming ultrathin 2D Pd/mSnO2 nanocomposites with thicknesses of 6-8 nm. Owing to the unique 2D mesoporous structure with rich oxygen defects and highly exposed metal-metal oxide interfaces, 2D Pd/mSnO2 exhibits excellent sensing performance toward acetone with high sensitivity, a short response time, and good selectivity under low working temperature (100 °C). This fast and convenient microexplosion synthesis strategy opens up the possibility of constructing 2D porous functional materials for various applications including high-performance gas sensors.

Construction of dual-chiral covalent organic frameworks for enantioselective separation.

Developing novel chiral stationary phases (CSPs) with versatility is of great importance in enantiomer separation. This study fabricated a dual-chiral covalent organic framework (PA-CA COF) via successive post-synthetic modifications. The chiral trans-1,2-cyclohexanediamine (CA) and (D)-penicillamine (PA) groups were periodically aligned within nanochannels of the COF, allowing selective recognition of enantiomers through intermolecular interactions. It can be a versatile high-performance liquid chromatography (HPLC) CSP for separating a wide range of enantiomers, including chiral pharmaceutical intermediates and chiral drugs. With separation performance comparable to commercial chiral columns and even greater versatility, the PA-CA COF@SiO2 column held promise for practical applications. Chiral separation results combined with molecular simulation indicated that the mixed mode of PA and CA resulted in the broad separation capability of PA-CA COF. The introduction of the dual-chiral COFs concept opens up a new avenue for chiral recognition and separation, holding great potential for practical enantiomer separation.

Physiology and transcriptomic analysis revealed the mechanism of silicon promoting cadmium accumulation in Sedum alfredii Hance.

Silicon (Si) effectively promote the yield of many crops, mainly due to its ability to enhance plants resistance to stress. However, how Si helps hyperaccumulators to extract Cadmium (Cd) from soil has remained unclear. In this study, Sedum alfredii Hance (S. alfredii) was used as material to study how exogenous Si affected biomass, Cd accumulation, antioxidation, cell ultrastructure, subcellular distribution and changes in gene expression after Cd exposure. The study has shown that as Si concentration increases (1, 2 mM), the shoot biomass of plants increased by 33.1%-63.6%, the Cd accumulation increased by 31.9%-96.6%, and the chlorophyll, carotenoid content, photosynthetic gas exchange parameters significantly increased. Si reduced Pro and MDA, promoted the concentrations of SOD, CAT and POD to reduce antioxidant stress damage. In addition, Si promoted GSH and PC to chelate Cd in vacuoles, repaired damaged cell ultrastructure, improved the fixation of Cd and cell wall (especially in pectin), and reduced the toxic effects of Cd. Transcriptome analysis found that genes encoding Cd detoxification, Cd absorption and transport were up-regulated by Si supplying, including photosynthetic pathways (PSB, LHCB, PSA), antioxidant defense systems (CAT, APX, CSD, RBOH), cell wall biosynthesis such as pectinesterase (PME), chelation (GST, MT, NAS, GR), Cd absorption (Nramp3, Nramp5, ZNT) and Cd transport (HMA, PCR). Our result revealed the tentative mechanism of Si promotes Cd accumulation and enhances Cd tolerance in S. alfredii, and thereby provides a solid theoretical support for the practical use of Si fertilizer in phytoextraction.

Novel biaryloxazolidinone derivatives with broad-spectrum antibacterial activity, favorable drug-like profiles and in vivo efficacy against linezolid-resistant Staphylococcusaureus.

The emergence of multidrug-resistant bacteria along with a declining pipeline of clinically useful antibiotics has led to the urgent need for the development of more effective antibacterial agents to treat drug-resistant bacteria. We previously discovered compound OB-158 with potent antibacterial activity but exhibited poor oral bioavailability. Herein, a systematic structural optimization of OB-158 to improve pharmacokinetic profiles yielded 26 novel biaryloxazolidinone analogues, and their activities against Gram-positive S. aureus, multidrug resistant S. aureus and Enterococcus faecalis were evaluated. Remarkably, compound 8b was identified with potent antibacterial activity against S. aureus (MIC = 0.06 µg/mL), MSSA (MIC = 0.125 µg/mL), MRSA (MIC = 0.06 µg/mL), LRSA (MIC = 0.125 µg/mL) and LREFa (MIC = 0.5 µg/mL). Compound 8b was demonstrated as a promising candidate through druglikeness evaluation including metabolism in microsomes and plasma, Caco-2 cell permeability, plasma protein binding, cytotoxicity, and inhibition of CYP450 and human monoamine oxidase. Notably, compound 8b displayed excellent PK profile with appropriate T1/2 of 1.49 h, high peak plasma concentration (Cmax = 2320 ng/mL), high plasma exposure (AUC0-t = 8310 h ng/mL), and superior oral bioavailability (F = 68.1 %) in Sprague-Dawley rats. Ultimately, in vivo efficacy of compound 8b in a mouse model of LRSA systemic infection was also demonstrated. Taken together, compound 8b represents a promising drug candidate for the treatment of linezolid-resistant Gram-positive bacterial strains infection.

[Research progress of traditional Chinese medicine intervention for ulcerative colitis based on Notch1 signaling pathway].

Ulcerative colitis(UC) is one of the common gastrointestinal diseases worldwide. In recent years, the incidence of UC has been continuously increasing, seriously threatening the health of people globally. It thus has become an urgent problem that needs to be addressed. There is research evidence that intestinal mucosal barrier dysfunction, including changes in intestinal stem cell secretion lineage, mucosal layer damage, disruption of cell junctions, overactive immune function, and imbalanced gut microbiota, is an important pathogenic factor and molecular basis of UC. The Notch signaling pathway is a highly conserved signaling pathway in eukaryotes during evolution, which transmits signals through cell connections between adjacent cells, affecting a series of processes such as cell proliferation, differentiation, development, migration, and apoptosis. Therefore, the Notch signaling pathway can regulate intestinal stem cells, CD4~+T cells, innate lymphoid cells(ILCs), macrophages(MØ), and intestinal microbiota and thus affect the chemical, physical, immune, and biological mucosal barriers of the intestinal mucosa. Its function is extensive and unique, different from those signaling pathways that mainly focus on anti-inflammatory and antioxidant stress. It can explain the therapeutic effects of traditional Chinese medicine from different perspectives. This article reviewed the role of the Notch1 signaling pathway in the pathogenesis of UC and the relevant literature on the targeted prevention and treatment of UC with traditional Chinese medicine, so as to provide new targets and theoretical support for further research on the effective prevention and treatment of UC.

Developing hydrogels for gene therapy and tissue engineering.

Hydrogels are a class of highly absorbent and easily modified polymer materials suitable for use as slow-release carriers for drugs. Gene therapy is highly specific and can overcome the limitations of traditional tissue engineering techniques and has significant advantages in tissue repair. However, therapeutic genes are often affected by cellular barriers and enzyme sensitivity, and carrier loading of therapeutic genes is essential. Therapeutic gene hydrogels can well overcome these difficulties. Moreover, gene-therapeutic hydrogels have made considerable progress. This review summarizes the recent research on carrier gene hydrogels for the treatment of tissue damage through a summary of the most current research frontiers. We initially introduce the classification of hydrogels and their cross-linking methods, followed by a detailed overview of the types and modifications of therapeutic genes, a detailed discussion on the loading of therapeutic genes in hydrogels and their characterization features, a summary of the design of hydrogels for therapeutic gene release, and an overview of their applications in tissue engineering. Finally, we provide comments and look forward to the shortcomings and future directions of hydrogels for gene therapy. We hope that this article will provide researchers in related fields with more comprehensive and systematic strategies for tissue engineering repair and further promote the development of the field of hydrogels for gene therapy.

A Versatile Synthesis Platform Based on Polymer Cubosomes for a Library of Highly Ordered Nanoporous Metal Oxides Particles.

Polymer cubosomes (PCs) have well-defined inverse bicontinuous cubic mesophases formed by amphiphilic block copolymer bilayers. The open hydrophilic channels, large periods, and robust physical properties of PCs are advantageous to many host-guest interactions and yet not fully exploited, especially in the fields of functional nanomaterials. Here, the self-assembly of poly(ethylene oxide)-block-polystyrene block copolymers is systematically investigated and a series of robust PCs is developed via a cosolvent method. Ordered nanoporous metal oxide particles are obtained by selectively filling the hydrophilic channels of PCs via an impregnation strategy, followed by a two-step thermal treatment. Based on this versatile PC platform, the general synthesis of a library of ordered porous particles with different pore structures 3 ¯ $\bar{3}$ 3 ¯ $\bar{3}$ , tunable large pore size (18-78 nm), high specific surface areas (up to 123.3 m2 g-1 for WO3) and diverse framework compositions, such as transition and non-transition metal oxides, rare earth chloride oxides, perovskite, pyrochlore, and high-entropy metal oxides is demonstrated. As typical materials obtained via this method, ordered porous WO3 particles have the advantages of open continuous structure and semiconducting properties, thus showing superior gas sensing performances toward hydrogen sulfide.