"All in one" lipid-polymer nanodelivery system for gene therapy of ischemic diseases.

Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H2O2-induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn't induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.

Radiogenomics based survival prediction of small-sample glioblastoma patients by multi-task DFFSP model.

In this paper, the multi-task dense-feature-fusion survival prediction (DFFSP) model is proposed to predict the three-year survival for glioblastoma (GBM) patients based on radiogenomics data. The contrast-enhanced T1-weighted (T1w) image, T2-weighted (T2w) image and copy number variation (CNV) is used as the input of the three branches of the DFFSP model. This model uses two image extraction modules consisting of residual blocks and one dense feature fusion module to make multi-scale fusion of T1w and T2w image features as backbone. Also, a gene feature extraction module is used to adaptively weight CNV fragments. Besides, a transfer learning module is introduced to solve the small sample problem and an image reconstruction module is adopted to make the model anatomy-aware under a multi-task framework. 256 sample pairs (T1w and corresponding T2w MRI slices) and 187 CNVs of 74 patients were used. The experimental results show that the proposed model can predict the three-year survival of GBM patients with the accuracy of 89.1 %, which is improved by 3.2 and 4.7 % compared with the model without genes and the model using last fusion strategy, respectively. This model could also classify the patients into high-risk and low-risk groups, which will effectively assist doctors in diagnosing GBM patients.

Cu(II)-baicalein enhance paracrine effect and regenerative function of stem cells in patients with diabetes.

The development of engineered or modified autologous stem cells is an effective strategy to improve the efficacy of stem cell therapy. In this study, the stemness and functionality of adipose stem cells derived from type 1 diabetic donors (T1DM-ASC) were enhanced by treatment with Cu(II)-baicalein microflowers (Cu-MON). After treatment with Cu-MON, T1DM-ASC showed enhanced expression of the genes involved in the cytokine-cytokine receptor interaction pathway and increased cytokine secretion. Among the top 13 differentially expressed genes between T1DM-ASC and Cu-MON-treated T1DM-ASC (CMTA), some genes were also expressed in HUVEC, Myoblast, Myofibroblast, and Vascular Smooth Muscle cells, inferring the common role of these cell types. In vivo experiments showed that CMTA had the same therapeutic effect as adipose-derived stem cells from non-diabetic donors (ND-ASC) at a 15% cell dose, greatly reducing the treatment cost. Taken together, these findings suggest that Cu-MON promoted angiogenesis by promoting the stemness and functionality of T1DM-ASC and influencing multiple overall repair processes, including paracrine effects.

The experience of fertility concerns in patients with testicular cancer: a qualitative study.

BACKGROUND: Testicular cancer usually occurs in young adult men between the ages of 20 and 40 years, which largely coincides with the age of men's reproductive intentions. However, a serious side effect of testicular cancer therapy could reduce the fertility of patients. PURPOSE: To explore the experience of fertility concerns in patients with testicular cancer. METHODS: A phenomenological research was conducted on 12 patients with testicular cancer. Data collection was from May 2023 to August 2023, and Colaizzi analysis method was used to analyze the data. RESULTS: Four themes were found: (1) multiple worries and negative emotions, (2) fertility decision-making faces many challenges, (3) self-coping strategies for facing fertility concerns, (4) unmet supportive care needs. CONCLUSION: Medical staff should pay attention to the fertility needs of patients with testicular cancer and provide relevant interventions and support to reduce their fertility concerns.

Epinephelus coioides Sec3 promotes Singapore grouper iridovirus infection by negatively regulates immune response.

Exocyst, a protein complex, plays a crucial role in various cellular functions, including cell polarization, migration, invasion, cytokinesis, and autophagy. Sec3, known as Exoc1, is a key subunit of the Exocyst complex and can be involved in cell survival and apoptosis. In this study, two subtypes of Sec3 were isolated from Epinephelus coioides, an important marine fish in China. The role of E. coioides Sec3 was explored during Singapore grouper iridovirus (SGIV) infection, an important pathogen of marine fish which could induce 90 % mortality. E. coioides Sec3 sequences showed a high similarity with that from other species, indicating the presence of a conserved Sec3 superfamily domain. E. coioides Sec3 mRNA could be detected in all examined tissues, albeit at varying expression levels. SGIV infection could upregulate E. coioides Sec3 mRNA. Upregulated Sec3 significantly promoted SGIV-induced CPE, and the expressions of viral key genes. E. coioides Sec3 could inhibit the activation of NF-κB and AP-1, as well as SGIV-induced cell apoptosis. The results illustrated that E. coioides Sec3 promotes SGIV infection by regulating the innate immune response.

HBXIP induces PARP1 via WTAP-mediated m6A modification and CEBPA-activated transcription in cisplatin resistance to hepatoma.

Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA-binding protein that is involved in various biological functions, including DNA damage repair and transcription regulation. It plays a crucial role in cisplatin resistance. Nevertheless, the exact regulatory pathways governing PARP1 have not yet been fully elucidated. In this study, we present evidence suggesting that the hepatitis B X-interacting protein (HBXIP) may exert regulatory control over PARP1. HBXIP functions as a transcriptional coactivator and is positively associated with PARP1 expression in tissues obtained from hepatoma patients in clinical settings, and its high expression promotes cisplatin resistance in hepatoma. We discovered that the oncogene HBXIP increases the level of PARP1 m6A modification by upregulating the RNA methyltransferase WTAP, leading to the accumulation of the PARP1 protein. In this process, on the one hand, HBXIP jointly activates the transcription factor ETV5, promoting the activation of the WTAP promoter and further facilitating the promotion of the m6A modification of PARP1 by WTAP methyltransferase, enhancing the RNA stability of PARP1. On the other hand, HBXIP can also jointly activate the transcription factor CEBPA, enhance the activity of the PARP1 promoter, and promote the upregulation of PARP1 expression, ultimately leading to enhanced DNA damage repair capability and promoting cisplatin resistance in hepatoma. Notably, aspirin inhibits HBXIP, thereby reducing the expression of PARP1. Overall, our research revealed a novel mechanism for increasing PARP1 abundance, and aspirin therapy could overcome cisplatin resistance in hepatoma.

Construction and Modification of Nitrogen-Rich Polycyclic Frameworks: A Promising Fused Tricyclic Host-Guest Energetic Material with Heat Resistance, High Energy, and Low Sensitivity.

The construction and modification of novel energetic frameworks to achieve an ideal balance between high energy density and good stability are a continuous pursuit for researchers. In this work, a fused [5,6,5]-tricyclic framework was utilized as the energetic host to encapsulate the oxidant molecules for the first time. A series of new pyridazine-based [5,6] and [5,6,5] fused polycyclic nitrogen-rich skeletons and their derivatives were designed and synthesized. Two strategies, amino oxidation and host-guest inclusion, were used to modify the skeleton in only one step. All compounds exhibit good comprehensive properties (Td (onset) > 200 °C, ρ > 1.85 g cm-3, Dv > 8400 m s-1, IS > 20 J, FS > 360 N). Benefiting from the pyridazine-based fused tricyclic structure with more hydrogen bonding units and larger conjugated systems, the first example of [5,6,5]-tricyclic host-guest energetic material triamino-9H-pyrazolo[3,4-d][1,2,4]triazolo[4,3-b]pyridazine-diperchloric acid (10), shows high decomposition temperature (Td (onset) = 336 °C), high density and heats of formation (ρ = 1.94 g cm-3, ΔHf = 733.4 kJ mol-1), high detonation performance (Dv = 8820 m s-1, P = 36.2 GPa), high specific impulse (Isp = 269 s), and low sensitivity (IS = 30 J, FS > 360 N). The comprehensive performance of 10 is superior to that of high-energy explosive RDX and heat-resistant explosives such as HNS and LLM-105. 10 has the potential to become a comprehensive advanced energetic material that simultaneously satisfies the requirements of high-energy and low-sensitivity explosives, heat-resistant explosives, and solid propellants. This work may give new insights into the construction and modification of a nitrogen-rich polycyclic framework and broaden the applications of fused polycyclic framework for the development of host-guest energetic materials.

Tannic acid modified keratin/sodium alginate/carboxymethyl chitosan biocomposite hydrogels with good mechanical properties and swelling behavior.

Natural polymer-based hydrogels have demonstrated great potential as wound-healing dressings. They help to maintain a moist wound environment as well as promote faster healing. In this work, a multifunctional hydrogel was prepared using keratin, sodium alginate, and carboxymethyl chitosan with tannic acid modification. Micro-morphology of hydrogels has been performed by scanning electron microscopy. Fourier Transform Infrared Spectroscopy reveals the presence of hydrogen bonding. The mechanical properties of the hydrogels were examined using a universal testing machine. Furthermore, we investigated several properties of the modified hydrogel. These properties include swelling rate, water retention, anti-freezing properties, antimicrobial and antioxidant properties, hemocompatibility evaluation and cell viability test in vitro. The modified hydrogel has a three-dimensional microporous structure, the swelling rate was 1541.7%, the elastic modulus was 589.74 kPa, the toughness was 211.74 kJ/m3, and the elongation at break was 75.39%, which was similar to the human skin modulus. The modified hydrogel also showed inhibition of S. aureus and E. coli, as well as a DPPH scavenging rate of 95%. In addition, the modified hydrogels have good biological characteristics. Based on these findings, the K/SA/CCS hydrogel holds promise for applications in biomedical engineering.

Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth.

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.

Me3SiBr-promoted cascade electrophilic thiocyanation/cyclization of ortho-alkynylanilines to synthesize indole derivatives.

A Lewis acid-promoted electrophilic thiocyanation/cyclization of ortho-alkynylanilines for the synthesis of indole derivatives has been developed. The reaction utilizes Me3SiBr as the Lewis acid and N-thiocyanatosuccinimide as the thiocyanation reagent. A series of 2-aryl-3-thiocyanato indoles were prepared in moderate to high yields under mild conditions without metals and oxidants. It provides an efficient protocol for the construction of the indole skeleton and C-SCN and C-N bonds in one step as well.

Floating MIL-88A(Fe)@expanded perlites catalyst for continuous photo-Fenton degradation toward tetracyclines under artificial light and real solar light.

In this work, MIL-88A(Fe) was immobilized onto the expanded perlites to fabricate the floating MIL-88A(Fe)@expanded perlites (M@EP) catalyst via high throughput batch synthesis method under room temperature. The as-prepared M@EP could efficiently activate H2O2 to achieve 100% tetracycline antibiotics (TCs) removal under both artificial low power UV light (UVL) and real sunlight (SL) irradiation. The toxicological evaluation, growth experiment of mung beans and antimicrobial estimation revealed the decreasing aquatic toxicity of the TCs intermediates compared to those of the pristine TCs. A self-designed continuous bed reactor was employed to investigate the long-term operation of the M@EP. The findings demonstrated that the antibiotics mixture can be continuously degraded up to 7 days under UVL and 5 daytimes under SL irradiation, respectively. More importantly, ca. 76.9% and 81.6% of total organic carbon (TOC) removal efficiencies were accomplished in continuous bed reactor under UVL and SL irradiation, respectively. This work advances the immobilized MOFs on floating supports for their practical application in large-scale wastewater purification through advanced oxidation processes. ENVIRONMENTAL IMPLICATION: This work presented the high throughput production and photo-Fenton degradation application of floating MIL-88A(Fe)@expanded perlites (M@EP). Three tetracycline antibiotics (TCs) were selected as model pollutants to test the degradation ability of M@EP in batch experiment and continuous operation under artificial light and solar light. The complete TCs degradation could be accomplished in self-designed device up to 7 d under UV light and 5 d under real solar light. This work tapped a new door to push MOFs-based functional materials in the real water purification.

[Transcriptional regulation mechanism of differential accumulation of flavonoids in different varieties of Lonicera macranthoides based on metabonomics and transcriptomics].

This study aims to explore the molecular regulatory mechanism of the differential accumulation of flavonoids between 'Xianglei' and the wild type of Lonicera macranthoides. The flowers, stems, and leaves of the two varieties of L. macranthoides were collected. Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS) and high-throughput sequencing(RNA-seq) were employed to screen out the differential flavonoids, key differentially expressed genes(DEGs) and transcription factors(TFs). Fourteen DEGs were randomly selected for verification by qRT-PCR. The results showed that a total of 17 differential flavonoids were obtained, including naringin chalcone, apigenin, and quercetin. The transcriptomic analysis predicted 19 DEGs associated with flavonoids, including 2 genes encoding chitin synthase(CHS) and 3 genes encoding chalcone isomerase(CHI). The regulatory network analysis and weighted gene co-expression network analysis(WGCNA) screen out the key enzyme genes CHS1, FLS1, and HCT regulating the accumulation of flavonoids. MYB12 and LBD4 may be involved in the biosynthesis of flavonoids by regulating the expression of key enzyme genes CHS1, FLS1, and HCT. The qRT-PCR and RNA-seq results were similar regarding the expression patterns of the 14 randomly selected DEGs. This study preliminarily analyzed the transcriptional regulatory mechanism for the differential accumulation of flavonoids in the two varieties of L. macranthoides and laid a foundation for further elucidating the regulatory effects of key enzyme genes and TFs on the accumulation of flavonoids.

Organophotocatalytic Remote Thiocyanation Reaction via Ring-Opening Functionalization of Cycloalkanols.

The remote C(sp3)-SCN bond formation via ring-opening functionalization of cycloalkanols with N-thiocyanatosaccharin as the precursor of SCN radicals and pyrylium salt as the organic photocatalyst under visible light has been developed. Thus, various terminal keto thiocyanates were prepared without transition metals and oxidants in moderate to good yields. The simplicity, wide substrate scope and mild conditions feature its synthetic application capability.

Analysis of quality evaluation and optimal harvest period of Aurantii Fructus from different sources using UHPLC-Q-TOF-MS/MS.

INTRODUCTION: The active constituents in Aurantii Fructus sourced from different regions within Hunan Province exhibit variations, with certain samples demonstrating substandard quality. OBJECTIVES: The aim of this study is to conduct a comparative analysis of the chemical composition and quality of Aurantii Fructus from various sources, establish a robust methodology for quality evaluation, and determine the optimal harvesting period. MATERIALS AND METHODS: The components of Aurantii Fructus were qualitatively analyzed using a non-targeted metabolomics approach. Multivariate statistical analyses were conducted to identify potential markers, enabling qualitative and quantitative evaluation of the quality and optimal harvest period of Aurantii Fructus. RESULTS: Overall, 155 compounds were identified in Aurantii Fructus, with Huangpi exhibiting the highest number of components. Eleven potential markers were selected to assess the quality of Aurantii Fructus. The average content of Huangpi was the highest, indicating a high level of similarity. The samples' overall scores were ordered as follows: Huangpi > Xiangcheng > Choucheng > Daidai. Anren and Changde's Huangpi exhibited high contents, being rich in chemical components, resulting in favorable scores. Similarly, Changde's Xiangcheng displayed significant medicinal value. As the harvest time was delayed, there was an increase in fruit size, accompanied by thinner peels and a continuous decrease in the contents of potential markers. The best harvest period of Aurantii Fructus was within 1 week before and after the Lesser Heat. CONCLUSION: The present study establishes a precise and efficient method for evaluating the quality of Aurantii Fructus, thereby providing more comprehensive insights into its composition. This research lays the foundation for subsequent development and utilization of Aurantii Fructus.

Influence and mechanism of solids on the air pressure fluctuations on the building drainage system.

The conventional building drainage system was constructed based on the theory of two-phase flow involving water and air. However, the drainage system contained a more intricate three-phase flow, encompassing water, air, and solids, which was relatively overlooked in research. This study addressed the impact of solids on pressure fluctuations, air flow rates, and hydraulic jump fullness within the drainage system, considering three factors: the mass factor, cross-section factor, and viscosity. The investigation was conducted within a single-stack system using both experimental methods and CFD simulations. The findings revealed a positive correlation between both positive and negative pressures and above three factors. The mass factor and the cross-section factor had a more significant impact on the negative pressure of the system. The maximum growth rates of negative pressure extremes under different mass and cross-section factors reached 7.72 and 16.52%, respectively. In contrast, the viscosity of fecal sludge had a slightly higher effect on the positive pressure fluctuation of the drainage system, with the maximum growth rate of positive pressure extremes at 3.41%.

Etiological characteristics of acute respiratory infections during the SARS-CoV-2 epidemic in Guizhou Province, China.

OBJECTIVE: Acute respiratory infections are a major global public health concern. However, there are few epidemiological studies investigating pathogens associated with respiratory tract infections in Guizhou Province, China. METHODS: We collected 17,850 blood samples from Guizhou Provincial People's Hospital between November 2018 and May 2023 to investigate the epidemiological characteristics of respiratory pathogens and their spread during the SARS-CoV-2 epidemic in Guizhou Province. RESULTS: We identified influenza virus and Mycoplasma pneumoniae as the predominant pathogens involved in acute respiratory infections in the study area. Immunoglobulin M positivity for respiratory syncytial virus, influenza virus, and M. pneumoniae showed a strong correlation with the clinical diagnosis of pneumonia. Seasonal epidemic patterns were observed for influenza A and B viruses. Following the SARS-CoV-2 outbreak, there was a significant decrease in the positive rates for most respiratory pathogens, particularly influenza A and B, Legionella pneumophila, and respiratory syncytial virus. CONCLUSION: This retrospective study contributes to the epidemiological evidence regarding respiratory pathogens in Guizhou Province, thereby enhancing the surveillance network for respiratory pathogens in China and providing valuable guidance for local hospitals.

Research progress of the chemokine/chemokine receptor axes in the oncobiology of multiple myeloma (MM).

BACKGROUND: The incidence of multiple myeloma (MM), a type of blood cancer affecting monoclonal plasma cells, is rising. Although new drugs and therapies have improved patient outcomes, MM remains incurable. Recent studies have highlighted the crucial role of the chemokine network in MM's pathological mechanism. Gaining a better understanding of this network and creating an overview of chemokines in MM could aid in identifying potential biomarkers and developing new therapeutic strategies and targets. PURPOSE: To summarize the complicated role of chemokines in MM, discuss their potential as biomarkers, and introduce several treatments based on chemokines. METHODS: Pubmed, Web of Science, ICTRP, and Clinical Trials were searched for articles and research related to chemokines. Publications published within the last 5 years are selected. RESULTS: Malignant cells can utilize chemokines, including CCL2, CCL3, CCL5, CXCL7, CXCL8, CXCL12, and CXCL13 to evade apoptosis triggered by immune cells or medication, escape from bone marrow and escalate bone lesions. Other chemokines, including CXCL4, CCL19, and CXCL10, may aid in recruiting immune cells, increasing their cytotoxicity against cancer cells, and inducing apoptosis of malignant cells. CONCLUSION: Utilizing anti-tumor chemokines or blocking pro-tumor chemokines may provide new therapeutic strategies for managing MM. Inspired by developed CXCR4 antagonists, including plerixafor, ulocuplumab, and motixafortide, more small molecular antagonists or antibodies for pro-tumor chemokine ligands and their receptors can be developed and used in clinical practice. Along with inhibiting pro-tumor chemokines, studies suggest combining chemokines with chimeric antigen receptor (CAR)-T therapy is promising and efficient.

Efficient pollutant degradation by peroxymonosulfate activated by a Co/Mn metal-organic framework.

In this work, a three-dimensional bimetallic metal-organic framework (BMOF), BUC-101 (Co/Mn-H6chhc, H6chhc = cis-1,2,3,4,5,6-cyclohexane-hexacarboxylic acid, BUC = Beijing University of Civil Engineering and Architecture) was synthesized by a one-pot solvothermal method and characterized in detail by single crystal X-ray diffraction (SCXRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) element mapping analysis. BUC-101 showed excellent catalytic peroxymonosulfate (PMS) activation performance to degrade rhodamine B (RhB) without energy input. In addition, BUC-101 can maintain good stability and recyclability during the PMS activation processes, in which 99.9% RhB degradation efficiencies could be accomplished in 5 operational runs. The possible PMS activation and RhB degradation mechanisms of the BUC-101/PMS system were proposed and affirmed.

Energy-Efficient Electrosynthesis of High Value-Added Active Chlorine Coupled with H2 Generation from Direct Seawater Electrolysis through Decoupling Electrolytes.

Direct saline (seawater) electrolysis is a well-recognized system to generate active chlorine species for the chloride-mediated electrosynthesis, environmental remediation and sterilization over the past few decades. However, the large energy consumption originated from the high cell voltage of traditional direct saline electrolysis system, greatly restricts its practical application. Here, we report an acid-saline hybrid electrolysis system for energy-saving co-electrosynthesis of active chlorine and H2. We demonstrate that this system just requires a low cell voltage of 1.59 V to attain 10 mA cm-2 with a large energy consumption decrease of 27.7 % compared to direct saline electrolysis system (2.20 V). We further demonstrate that such acid-saline hybrid electrolysis system could be extended to realize energy-saving and sustainable seawater electrolysis. The acidified seawater in this system can absolutely avoid the formation of Ca/Mg-based sediments that always form in the seawater electrolysis system. We also prove that this system in the half-flow mode can realize real-time preparation of active chlorine used for sterilization and pea sprout production.