Synergistic dual cell therapy for atherosclerosis regression: ROS-responsive Bio-liposomes co-loaded with Geniposide and Emodin.

The development of nanomaterials for delivering natural compounds has emerged as a promising approach for atherosclerosis therapy. However, premature drug release remains a challenge. Here, we present a ROS-responsive biomimetic nanocomplex co-loaded with Geniposide (GP) and Emodin (EM) in nanoliposome particles (LP NPs) for targeted atherosclerosis therapy. The nanocomplex, hybridized with the macrophage membrane (Møm), effectively evades immune system clearance and targets atherosclerotic plaques. A modified thioketal (TK) system responds to ROS-rich plaque regions, triggering controlled drug release. In vitro, the nanocomplex inhibits endothelial cell apoptosis and macrophage lipid accumulation, restores endothelial cell function, and promotes cholesterol effluxion. In vivo, it targets ROS-rich atherosclerotic plaques, reducing plaque area ROS levels and restoring endothelial cell function, consequently promoting cholesterol outflow. Our study demonstrates that ROS-responsive biomimetic nanocomplexes co-delivering GP and EM exert a synergistic effect against endothelial cell apoptosis and lipid deposition in macrophages, offering a promising dual-cell therapy modality for atherosclerosis regression.

Gelation of crocodile myofibrillar protein - κ-carrageenan mixtures in two low-NaCl solution.

Crocodile meat is a novel reptile meat source, but its processing method is rare. This study investigated the effect of κ-carrageenan addition and partial substitution of NaCl on the gel properties of crocodile myofibrillar protein (CMP). Result showed that CMP formed gel when temperature above 60 ℃. The water-holding capacity, gel strength, denaturation degree, sulfhydryl content covalent bond and hydrophobic bond of gel in KCl solution were significantly higher than those in CaCl2 solution (P < 0.05). K+ induced CMP to form a tight network structure with uniform small pores though covalent and hydrophobic bonds, but the gel properties were reduced by κ-carrageenan. In CaCl2 solution, κ-carrageenan improved the gel structure by filling the protein network through hydrogen bonding. Therefore, it can be concluded that KCl is better than CaCl2 in the manufacturing of low-sodium crocodile foods. Moreover, κ-carrageenan was only beneficial to gel quality in CaCl2 solution.

A rat model established by simulating genetic-environmental interactions recapitulates human Alzheimer's disease pathology.

BACKGROUND: In humans, Alzheimer's disease (AD) is typically sporadic in nature, and its pathology is usually influenced by extensive factors. The study established a rat model based on the genetic-environmental interaction. METHODS: A rat model was established by transduction of an adeno-associated virus combined with acrolein treatment. Rats were assigned to the normal control (NC), acrolein group, AAV (-) group, AAV-APP group, and AAV-APP/acrolein group. The success of model construction was verified in multiple ways, including by assessing cognitive function, examining microstructural changes in the brain in vivo, and performing immunohistochemistry. The contribution of genetic (APP mutation) and environmental (acrolein) factors to AD-like phenotypes in the model was explored by factorial analysis. RESULTS: 1) The AAV-APP/acrolein group showed a decline in cognitive function, as indicated by a reduced gray matter volume in key cognition-related brain areas, lower FA values in the hippocampus and internal olfactory cortex, and Aß deposition in the cortex and hippocampus. 2) The AAV-APP group also showed a decline in cognitive function, although the group exhibited atypical brain atrophy in the gray matter and insignificant Aß deposition. 3) The acrolein group did not show any significant changes in Aß levels, gray matter volume, or cognitive function. 4) The genetic factor (APP mutation) explained 39.74% of the AD-like phenotypes in the model factors, and the environmental factor (acrolein exposure) explained 33.3%. CONCLUSIONS: The genetic-environmental interaction rat model exhibited a phenotype that resembled the features of human AD and will be useful for research on AD.

Chemical Comparison and Identification of Xanthine Oxidase Inhibitors of Dioscoreae Hypoglaucae Rhizoma and Dioscoreae Spongiosae Rhizoma by Chemometric Analysis and Spectrum-Effect Relationship.

Dioscoreae hypoglaucae Rhizoma (DH) and Dioscoreae spongiosae Rhizoma (DS) are two similar Chinese herbal medicines derived from the Dioscorea family. DH and DS have been used as medicines in China and other Asian countries for a long time, but study on their phytochemicals and bioactive composition is limited. This present study aimed to compare the chemical compositions of DH and DS, and explore the anti-xanthine oxidase components based on chemometric analysis and spectrum-effect relationship. Firstly, an HPLC method was used to establish the chemical fingerprints of DH and DS samples, and nine common peaks were selected. Then, hierarchical clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were employed to compare and discriminate DH and DS samples based on the fingerprints data, and four steroidal saponins compounds (protodioscin, protogracillin, dioscin, gracillin) could be chemical markers responsible for the differences between DH and DS. Meanwhile, the anti-xanthine oxidase activities of these two herbal medicines were evaluated by xanthine oxidase inhibitory assay in vitro. Pearson correlation analysis and partial least squares regression analysis were subsequently used to investigate the spectrum-effect relationship between chemical fingerprints and xanthine oxidase inhibitory activities. The results showed that four steroidal saponins, including protodioscin, protogracillin, methyl protodioscin and pseudoprogracillin could be potential anti-xanthine oxidase compounds in DH and DS. Furthermore, the xanthine oxidase inhibitory activities of the four selected inhibitors were validated by anti-xanthine oxidase inhibitory assessment and molecular docking experiments. The present work provided evidence for understanding of the chemical differences and the discovery of the anti-xanthine oxidase constituent of DH and DS, which could be useful for quality evaluation and bioactive components screening of these two herbal medicines.

Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy.

PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE-/- mice.

Clinical efficacy of laparoscopic closed hernia ring combined with a patch repair for Gilbert type III indirect inguinal hernia.

Purpose: The incidence of seroma and postoperative pain after Gilbert type III inguinal hernia repair is high. To reduce postoperative complications, this study investigated the clinical efficacy of laparoscopic closed hernia ring combined with a patch repair for Gilbert type III indirect inguinal hernia. Methods: Through a prospective randomized controlled study, a total of 193 patients with Gilbert type III indirect inguinal hernia admitted to Nanchong Central Hospital affiliated with Chuanbei Medical College from May 2020 to December 2021 were selected and randomly divided into the inner ring closed group (85 patients) and the inner ring non-closed group (95 patients). The patients in both groups underwent laparoscopic tension-free repair of their inguinal hernias. General information such as operative time, postoperative hospital stay, and hospital cost were compared between the two groups, and the patients were followed up at 1, 7, 14, 21, and 28 days and then 3, 6, and 12 months after surgery to compare complications such as incidence of seroma, volume of the seroma fluid, incidence of pain, and visual analogue scale (VAS) pain score. Results: There was no conversion to open procedures in any of the patients. The operation time of the closed group was significantly longer than that of the non-closed group (64.2 ± 12.2 vs. 55.3 ± 9.5 min, P < 0.01). The proportion of patients with postoperative pain in the two groups was 39 (46%) vs. 59 (62%), P = 0.029 on 7 days; 17 (20%) vs. 33 (35%), P = 0.028 on 14 days; and 6 (7%) vs. 22 (23%), P = 0.003 on 21 days in the postoperative closed group and was significantly lower than that in the non-closed group, while we found that the non-closed group had a higher VAS pain score than that of the closed group (2.36 ± 0.61 vs. 1.95 ± 0.71, P = 0.003 on 7 days and 2.12 ± 0.49 vs. 1.65 ± 0.49, P = 0.002 on 14 days) after surgery according to the statistical results of the VAS pain score. The incidence of postoperative seroma and the amount of seroma fluid decreased gradually in both groups, but when comparing the two groups, the proportion of cases of seroma in the closed group on 7 days [45 (53%) vs. 79 (83%), P < 0.01]; 14 days [23 (27%) vs. 43 (45%), P = 0.011]; and 21 days [10 (12%) vs. 29 (31%), P = 0.002] after the operation were significantly less than that in the non-closed group. For the comparison of the amount of seroma fluid between the groups, the seroma fluid volume in the non-closed group was greater than that in the closed group (34.48 ± 20.40 vs. 43.87 ± 16.40 ml, P = 0.006, 7 days) and (21.79 ± 8.42 vs. 30.74 ± 10.39 ml, P = 0.002, 14 days) after surgery. There were no differences in the length of stay, total hospital costs, or postoperative complications (urinary retention, intestinal obstruction, nausea, vomiting, bleeding, and infection) between the two groups, and the differences were not statistically significant (P > 0.05). The postoperative follow-up period was 3-20 months, and no chronic pain or recurrence occurred during the postoperative follow-up period in either group. Conclusions: Closure of the hernia ring is safe and effective for laparoscopic hernia repair for Gilbert type III inguinal hernia, and it significantly reduces the incidence of postoperative seroma and further reduces the postoperative pain without increasing the risk of postoperative infection and recurrence.

Characteristics of bloodstream infection and initial antibiotic use in critically ill burn patients and their impact on patient prognosis.

To investigate the bacterial epidemiology of blood cultures taken during the treatment of critically ill burn patients, the use of antibiotics at admission and before the observation of positive blood cultures, and their effect on prognosis. A retrospective study method was used. From January 1, 2010, to December 31, 2019, burn patients who met the inclusion criteria and were treated at the Burn Department, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, were enrolled in the study. Data were collected from the patients' electronic medical records. General patient information, including length of hospital stay, length of intensive care unit (ICU) stay, in-hospital mortality, the bacteria epidemiological characteristics of blood cultures, and the use of antibiotics within 24 h after admission and before a positive blood culture was observed, was collected. Independent sample t tests and χ2 tests were used to compare the effects of a positive blood culture and the use of appropriate antibiotics within 24 h after admission and before the observation of a positive blood culture on prognosis. (1) The three most frequently detected bacteria in the blood cultures were Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, and the amount of K. pneumoniae detected increased gradually. (2) Compared with the group of patients who were negative for bloodstream infection , the positive bloodstream infection group had a larger total body burn surface area (TBSA) (t = - 5.097, P = 0.000) and third-degree burn area (t = - 5.133, P = 0.000), a significantly longer length of hospital stay (t = 3.003, P = 0.003) and the length of ICU stay (t = 4.258, P = 0.000), and a significantly higher rate of in-hospital mortality (χ2 = 8.485, P = 0.004). When K. pneumoniae was detected, the length of hospital stay (t = 2.148, P = 0.035) and the length of ICU stay (t = 2.880, P = 0.005) were significantly prolonged. (3) The two antibiotics that were most frequently used in patients with acute burns within 24 h after admission were lincomycin (90 cases, 29.32%) and carbapenems (79 cases, 25.73%). Comparing the clinical characteristics of the lincomycin group and the carbapenem group, the TBSA (t = - 3.34, P = 0.001) and the third-degree burn area (t = - 6.08, P = 0.000) of the patients in the carbapenem group were larger, and the length of hospital stay (t = - 2.136, P = 0.035) and length of ICU stay (t = - 5.18, P = 0.000) were longer, but the difference in in-hospital mortality was not statistically significant (χ2 = 1.983, P = 0.159). (4) Comparing the group with appropriate initial antibiotic use within 24 h of admission to the inappropriate use group, the TBSA (t = - 0.605, P = 0.547), the third-degree burn area (t = 0.348, P = 0.729), the length of hospital stay (t = - 0.767, P = 0.445), the length of ICU stay (t = - 0.220, P = 0.827) and in-hospital mortality (χ2 = 1.271, P = 0.260) were not significantly different. (5) Comparing the group with appropriate antibiotic use before a positive blood culture was observed to the group with inappropriate antibiotic use, the TBSA (t = - 0.418, P = 0.677), the third-degree burn area (t = 0.266, P = 0.791), the length of hospital stay, the length of ICU stay (t = 0.995, P = 0.322) and in-hospital mortality (χ2 = 1.274, P = 0.259) were not significantly different. We found that patients with a positive blood culture had a larger burn area and a worse prognosis; that the greater the amount of K. pneumoniae in the bloodstream of burn patients was, the longer the hospital and ICU stays were; that whether appropriate antibiotics were administered to acute critical burn patients 24 h after admission had no effect on the prognosis; and that whether appropriate antibiotics were administered before a positive blood culture was observed had no effect on prognosis.

Incubation determines favorable microbial communities in Chinese alligator nests.

Nest materials are a major heat source due to rotting promoted by microbial activity. Additionally, they are a potential microbial source given their direct contact with eggshells. Microbial dynamics during incubation have been studied in wild birds; however, similar studies in reptiles remain elusive. Here, the study characterized microbial communities in the nest materials of Chinese alligator (Alligator sinensis) using high-throughput sequencing of bacterial 16S rRNA genes and fungal internal transcribed spacer (ITS) region sequences. The results showed that significant changes in the diversity and structure of microbial communities according to different incubation periods. The diversity and richness of bacterial species increased significantly over time, but the relative abundance of the most dominant bacteria in pre-incubation period, including some pathogenic bacteria, declined after incubation. In contrast, fungal species diversity and richness decreased significantly with time. Additionally, nest material composition significantly influenced microbial community structure rather than species diversity and richness. Notably, the fungal community structure showed a stronger response than bacteria to nest material composition, which varied due to differences in plant litter composition. Our results demonstrate the significant response of microbial community diversity and structure to differences in incubation periods and nest material composition in reptiles. It is further emphasized that the importance of incubation period in the conservation of the Chinese alligator and could inform similar studies in other reptiles and birds.

Sexual Dimorphism of the Gut Microbiota in the Chinese Alligator and Its Convergence in the Wild Environment.

The gut microbiota forms a complex microecosystem in vertebrates and is affected by various factors. As a key intrinsic factor, sex has a persistent impact on the formation and development of gut microbiota. Few studies have analyzed sexual dimorphism of gut microbiota, particularly in wild animals. We used 16S rRNA gene sequencing to analyze the gut microbiota of juvenile and adult Chinese alligators, and untargeted metabolomics to study serum metabolomes of adult alligators. We observed significant sexual differences in the community diversity in juvenile, but not adult, alligators. In terms of taxonomic composition, the phylum Fusobacteriota and genus Cetobacterium were highly abundant in adult alligators, similar to those present in carnivorous fishes, whereas the gut microbiota composition in juvenile alligators resembled that in terrestrial reptiles, indicating that adults are affected by their wild aquatic environment and lack sex dimorphism in gut microbiota. The correlation analysis revealed that the gut microbiota of adults was also affected by cyanobacteria in the external environment, and this effect was sex-biased and mediated by sex hormones. Overall, this study reveals sexual differences in the gut microbiota of crocodilians and their convergence in the external environment, while also providing insights into host-microbiota interactions in wildlife.

Adsorption and solidification of cadmium by calcium sulfate dihydrate (gypsum) in an aqueous environment: a dispersion-corrected DFT and ab initio molecular dynamics study.

Phosphogypsum is a by-product of phosphoric acid production by a wet-process and can be used to prepare adsorption materials to treat Cd(II) in sewage. Its main component is calcium sulfate dihydrate (gypsum). In the present study, incorporation and adsorption of cadmium on gypsum in an aqueous environment have been investigated using dispersion-corrected density functional theory, and the effect of different vacancy defects on the adsorption and doping of Cd on gypsum was also studied. The results show that Cd impurity defects can form more easily in gypsum crystals with Ca vacancy defects. The increase in both calcium vacancy defects and sulfate vacancy defects is beneficial to the incorporation of Cd in calcium sulfate dihydrate. In addition, the calcium vacancy defects on the gypsum surface can promote the adsorption of Cd(II), while sulfate vacancy defects on the gypsum surface inhibit the adsorption of Cd(II). Therefore, increasing the Ca vacancy defects of gypsum will help in improving the adsorption and curing properties of phosphogypsum for cadmium.

Effect of Ga1-xInxAs1-yPy Al-free asymmetric barrier on GaAs-based 808-nm laser diode.

A GaInAsP/GaAs/GaAsP Al-free laser with asymmetric potential barriers is designed theoretically to prevent carrier leakage. The band alignment demonstrates that a high height of the potential barrier decreases the leakage current. The internal quantum efficiency increases by increasing the injection efficiency, which is attributed to the decreasing electron potential barrier heights. Moreover, the threshold current and operating voltage decrease by adopting a novel barrier so that the output power and power conversion efficiency (PCE) increase. When the injection current is 5 kA/cm2, the PCE is 77.82% and the output power is 13.21 W. The physical mechanism of potential barrier heights affecting carrier transport is investigated, which will provide a theoretical basis for optimizing laser diodes.

A boronic acid-modified C60 derivatization reagent for the rapid detection of 3-monochloropropane-1,2-diol using matrix-assisted laser desorption/ionization-mass spectrometry.

RATIONALE: 3-Monochloropropane-1,2-diol (3-MCPD) is a well-known contaminant formed in food thermal processing, which could be found in a variety of foodstuffs. Due to its potential carcinogenicity, it was essential to quickly develop a rapid and high-throughput analytical method to monitor 3-MCPD in foodstuffs, which is described in this study. METHODS: 3-MCPD was extracted from foodstuffs and then was derivatized with a boronic acid-modified C60 (B-C60 ) through the boronic acid-diol reaction. Microwave heating was used to accelerate the derivatization reaction. Mass spectrometry (MS) analysis was conducted using matrix-assisted laser desorption/ionization-MS (MALDI-MS). The application of the method was validated using various smoked food samples. RESULTS: The chemical derivatization of 3-MCPD with B-C60 enabled the addition of a C60 -tag to 3-MCPD. High-throughput analysis of the sample within 0.5 h was realized. A good linear range from 0.02 to 1.5 µg mL-1 for 3-MCPD was obtained, with a detection limit of 0.005 µg mL-1 . The recoveries in spiked foodstuffs ranged from 85.4% to 115.1% with relative standard deviations of 2.0%-14.2%. This method was successfully applied to detect 3-MCPD in smoked foodstuffs. CONCLUSIONS: A quantitative method was developed for the detection of 3-MCPD in foodstuffs using B-C60 derivatization combined with MALDI-MS strategy. This proposed method may serve as a potential platform for the rapid and high-throughput analysis of 3-MCPD in foodstuffs for the purpose of food safety control.

C60-based chemical labeling strategy for the determination of polyamines in biological samples using matrix-assisted laser desorption/ionization mass spectrometry.

Bioactive polyamines play important roles in many biological processes such as gene expression, cell growth, protein synthesis, and signal transduction. Accurate determination of polyamines is helpful for studying their biological functions. Herein, a C60-based chemical labeling strategy was proposed for the determination of polyamines (putrescine, cadaverine, spermidine, and spermine) in biological samples using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). An N-hydroxysuccinimide ester functionalized C60 (NHS-C60) was used as a labeling reagent and the m/z of the labeled polyamines reached up to more than 900 Da, which avoided matrix interferences in the low m/z region. In addition, as NHS-C60 derivatives, mono- and bis-substituted polyamines were produced simultaneously, which benefited the qualitative analysis of polyamines. The analytical method was validated using NHS-C60 labeled polyamines in cells and mice feces samples. Good linearities were obtained with correlation coefficients ranging from 0.9786 to 0.9982. The limits of quantification were in the range of 0.68-1.48 pmol. Good reproducibility and reliability of our proposed method were confirmed by intra- and inter-day precisions ranged from 2.8 to 16.6%, and the recoveries ranged between 81.8 and 119.9%. Finally, the proposed method was applied to determine polyamines in cells and mice feces. Three polyamines were detected in the cells, and the contents of cadaverine and spermidine in the feces of high-fat diet mice were found to be significantly lower than those in the normal diet mice. The results show that the proposed NHS-C60 labeling coupled with MALDI MS strategy is suitable for the determination of polyamines in biological samples.

Preparation of zirconium arsenate-modified monolithic column for selective enrichment of phosphopeptides.

Protein phosphorylation is a crucial posttranslational modification for the regulation of many different biological functions. Selective enrichment of phosphopeptides from the complex biological samples is an essential step for the mass spectrometry analysis of protein phosphorylation. In this study, an arsenate functionalized monolithic column was first prepared by a single-step copolymerization of p-methacryloylaminophenylarsonic acid and ethylene dimethacrylate. Then the metal ions Zr4+ were attached onto the prepared monolithic column via metal-chelate complex formation by Zr4+ and arsenate groups. The obtained monolithic column was employed as a new sorbent for the phosphopeptide enrichment via immobilized metal affinity chromatography. Phosphopeptides analysis was realized by polymer monolith microextraction using this monolithic column coupled to both matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry. The proposed method exhibited a high selectivity for phosphopeptide enrichment in complex matrices, and was applied to the analysis of phosphopeptides in human serum and tryptic digests of rat brain proteins. Four phosphopeptides could be selectively captured from human serum and 2608 endogenous phosphopeptides were identified from the tryptic digests of rat brain proteins, indicating a satisfactory performance of this method for the enrichment of phosphopeptides from complex biological samples.

Expression patterns and a prognostic model of m6A-associated regulators in prostate adenocarcinoma.

Aim: To study the expression patterns and prognostic value of the m6A-associated regulators in prostate adenocarcinoma (PRAD). Materials & methods: The mRNA expression and clinical data were downloaded from 'The Cancer Genome Atlas database'. The m6A-associated variants were downloaded from m6AVar database, and combined with 14 common m6A regulators for subsequent analysis. One-way analysis of variance, univariate Cox regression analysis and least absolute shrinkage and selection operator algorithm were successively applied to obtain the ultimate regulators and prognostic model. Finally, consensus clustering, protein-protein interaction (PPI) and enrichment analysis were performed. Result: Nine regulators were obtained. PRAD patients could be classified into two risk groups and subclasses with significant survival differences by the prognostic model and consensus clustering, respectively. Conclusion: All these nine regulators were related to prognosis in PRAD, and could be used as clinical biomarkers.

[Brief discussion about role and measures of scientific fertilization in ecological cultivation of Chinese medicinal materials].

The ecological planting of Chinese medicinal materials is a cultivation technology that takes into account both ecological and economic benefits, and takes scientific planting technology as a guide to achieve the goal of high quality, high yield and efficiency of Chinese medicinal materials and the sustainable and healthy development of Chinese medicinal materials planting. Among them, scientific fertilization is an important measure to realize the ecological planting of Chinese medicinal materials. In recent years, the social economy has developed rapidly. In the production of Chinese herbal medicines, a large amount of chemical fertilizers and pesticides have been gradually used to increase short-term economic benefits. The unreasonable use of chemical fertilizers and pesticides has neglected the output, quality, safety, environmental pollution and environmental protection of medicinal materials. The impact of continuous development. Therefore, from the perspective of research on cultivation of Chinese medicinal materials, this article briefly describes the role and measures of scientific fertilization in ecological planting of Chinese medicinal materials. The roles of scientific fertilization in solving soil pollution and soil quality deterioration of Chinese herbal medicine cultivation, sustainable deve-lopment of Chinese herbal medicine production, unstable production quality of Chinese herbal medicine products, and quality safety are summarized separately. It is proposed measures based on the characteristics of soil fertilization, the growth and development characteristics of Chinese medicinal materials as the core, and the industrial planting model as the carrier to promote scientific fertilization in the cultivation of Chinese medicinal materials. Finally, the development direction of scientific fertilization and ecological plan-ting of traditional Chinese medicine is prospected, in order to provide support and reference for the development of ecological planting of traditional Chinese medicine.

On-Site and Quantitative Detection of Trace Methamphetamine in Urine/Serum Samples with a Surface-Enhanced Raman Scattering-Active Microcavity and Rapid Pretreatment Device.

Here, it reports a high-throughput detection method for reliably quantitative analysis of illegal drugs in complex biological samples by means of a surface-enhanced Raman scattering (SERS) active microcavity and rapid pretreatment device. Based on the well-made hemispherical microcavities that regularly distributed on a glass array, the quality-controllable microcavity device is fabricated by the compact self-assembly of core-shell nanopeanuts (CSNPs) onto the inside surface. Both the CSNPs with a quantifiable internal standard signal of crystal violet acetate anchored inside their gap and the well-made microcavity referred to the physical amplification of the microscale groove surface will do well in trace analysis, which will allow us to realize the accurately quantitative SERS analysis of targeted analytes spread on the bottom area of the microcavity array. As an example, 0.8 nM malachite green and 160 ppb methamphetamine (MATM) have been successively detected in a wide range as standard, while even 0.01 ppm MATM mixed in the urine/serum samples has been efficiently tested by the microcavity device equipped with a rapid pretreatment device (manual monolithic column syringe needle). All of the above suggest that the SERS-active microcavity equipped with a rapid pretreatment device has potential in the on-site quick test of trace amounts of illegal drugs in bodily fluid samples or other field analysis of food sanitation, environmental safety, and public health.

The association of serum vitamin K2 levels with Parkinson's disease: from basic case-control study to big data mining analysis.

Although it is known that inflammation is involved in Parkinson's disease (PD) pathogenesis and vitamin K2 (VK2) has anti-inflammatory effects, to date few studies have been reported on the relationship between VK2 and PD development. Herein we presented a case-control study involving 93 PD patients and 95 healthy controls. Overall, the serum VK2 level of PD patients (3.49 ± 1.68 ng/ml) was significantly lower than that of healthy controls (5.77 ± 2.71 ng/ml). When the PD patients were stratified by disease progression, we observed that the serum VK2 level of late stage patients was further decreased to 3.15 ± 1.18 ng/ml while the serum VK2 level of early stage patients was 3.92 ± 2.09 ng/ml. Furthermore, the curve analysis showed that the serum VK2 level decreased gradually with the increment of PD Hoehn-Yahr (H-Y) stage. We also confirmed the dysregulated inflammatory responses and coagulation cascades in PD patients by public dataset, which are associated to the decreased VK2 level. In summary, we found the serum VK2 level in PD patients is lower than that in healthy controls. The decrease of VK2 level may be related to the occurrence and progression of PD by loosening the regulation of inflammatory responses and coagulation cascades signal.

Downregulation of ST3GAL5 is associated with muscle invasion, high grade and a poor prognosis in patients with bladder cancer.

In patients with bladder cancer (BC), the association between ST3 ß-galactoside α-2,3-sialyltransferase 5 (ST3GAL5) expression and clinical outcomes, particularly regarding muscle-invasive disease, high tumor grade and prognosis, remain unknown. In the present study, the expression of ST3GAL5 and its association with clinical outcomes in patients with BC was analyzed using various public bioinformatics databases. The difference in ST3GAL5 expression between BC and healthy bladder tissues was also evaluated using data from the Oncomine database, The Cancer Genome Atlas and Gene Expression Omnibus database. The differences in ST3GAL5 expression between muscle invasive BC (MIBC) and non-muscle invasive BC (NMIBC), and high- and low-grade BC were also analyzed. Furthermore, genes that were positively co-expressed with ST3GAL5 in patients with BC were identified from the intersection between the Oncomine, Gene Expression Profiling Interactive Analysis 2 and UALCAN databases. Enrichment analysis by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome pathway enrichment analyses and a gene-concept network was performed using R package. Gene set enrichment analysis was also performed to assess the signaling pathways influenced by the high and low expression of ST3GAL5 in BC. The results indicated that ST3GAL5 expression was significantly lower in BC tissues compared with normal bladder tissues (P<0.05). Furthermore, ST3GAL5 expression in MIBC and high-grade BC was significantly lower compared with NMIBC and low-grade BC (P<0.05), respectively. The results from Kaplan-Meier survival analysis result demonstrated that ST3GAL5 downregulation was associated with poor survival in patients with BC (P<0.05). Taken together, these findings suggested that ST3GAL5 may be considered as an anti-oncogene in BC, could represent a potential predictive and prognostic biomarker for BC and may be a molecular target for tumor therapy.