Database-aided ultrahigh-performance liquid chromatography Q-Exactive-Orbitrap tandem mass spectrometry putatively identifies 16 unexpected compounds and three anticounterfeiting pharmacopoeia quality markers for Perillae Fructus.

RATIONALE: Perillae Fructus (PF) is a common traditional Chinese medicine (TCM) for the treatment of asthma. It has not been effectively characterized by rosmarinic acid (RosA), which is currently designed as the sole quality indicator in the Chinese Pharmacopoeia. METHODS: This study introduced a database-aided ultrahigh-performance liquid chromatography equipped with quadrupole-Exactive-Orbitrap mass spectrometry (UHPLC/Q-Exactive-Orbitrap MS/MS) technology to putatively identify the compounds in PF, followed by literature research, quantum chemical calculation, and molecular docking to screen potential quality markers (Q-markers) of PF. RESULTS: A total of 27 compounds were putatively identified, 16 of which had not been previously found from PF. In particular, matrine, scopolamine, and RosA showed relatively high levels of content, stability, and drug-likeness. They exhibited interactions with the asthma-related target and demonstrated the TCM properties of PF. CONCLUSIONS: The database-aided UHPLC/Q-Exactive-Orbitrap MS/MS can identify at least 27 compounds in PF. Of these, 16 compounds are unexpected, and three compounds (matrine, scopolamine, and RosA) should be considered anticounterfeiting pharmacopoeia Q-markers of PF.

The Post-Effects of the Authenticity of Rural Intangible Cultural Heritage and Tourists' Engagement.

Amidst the burgeoning interest in rural Intangible Cultural Heritage (ICH) tourism, this study, anchored in the Stimulus-Organism-Response (S-O-R) theoretical framework, chose Meizhou Island in Fujian Province as a case study to examine the impacts of tourists' perceptions of authenticity and their engagement levels on the destination image and loyalty towards rural ICH tourism. Utilizing Structural Equation Modeling (SEM) to analyze survey data, findings revealed that higher perceptions of a destination's preservation of original characteristics and traditional values correlate with a more favorable overall perception of the destination, albeit with smaller impact on emotional connections. Conversely, depth of tourist engagement was shown to enhance both understanding and emotional bonds with the destination. Further, familiarity with the destination was found to foster affection, thereby increasing the likelihood of repeat visits or recommendations. The more tourists know about a place, perceiving it as authentic, the more likely they are to remain loyal; similarly, deeper engagement enhances understanding and affection, increasing the probability of revisiting or recommending the place. These outcomes not only offer new insights into tourist behavior but also provide theoretical and practical guidance for the protection and development of rural ICH tourism, destination marketing, and management strategies, thus promoting the sustainable development of rural ICH tourism.

Alkylated EDTA potentiates antibacterial photodynamic activity of protoporphyrin.

Antibiotic resistance has garnered significant attention due to the scarcity of new antibiotics in development. Protoporphyrin IX (PpIX)-mediated photodynamic therapy shows promise as a novel antibacterial strategy, serving as an alternative to antibiotics. However, the poor solubility of PpIX and its tendency to aggregate greatly hinder its photodynamic efficacy. In this study, we demonstrate that alkylated EDTA derivatives (aEDTA), particularly C14-EDTA, can enhance the solubility of PpIX by facilitating its dispersion in aqueous solutions. The combination of C14-EDTA and PpIX exhibits potent antibacterial activity against Staphylococcus aureus (S. aureus) when exposed to LED light irradiation. Furthermore, this combination effectively eradicates S. aureus biofilms, which are known to be strongly resistant to antibiotics, and demonstrates high therapeutic efficacy in an animal model of infected ulcers. Mechanistic studies reveal that C14-EDTA can disrupt PpIX crystallization, increase bacterial membrane permeability and sequester divalent cations, thereby improving the accumulation of PpIX in bacteria. This, in turn, enhances reactive oxygen species (ROS) production and the antibacterial photodynamic activity. Overall, this effective strategy holds great promise in combating antibiotic-resistant strains.

Study on the performance and mechanism of cobaltous ion removal from water by a high-efficiency strontium-doped hydroxyapatite adsorbent.

In this study, a high-efficiency strontium-doped hydroxyapatite (Sr-HAP) adsorbent was synthesized by a sol-gel method for removing cobaltous ions (Co(II)) from water. The effects of adsorbent dose, initial solution pH, initial Co(II) concentration and temperature on the removal performance of Co(II) were investigated. Experimental results indicated that the optimum Sr-HAP dose was 0.30 g/50 mL solution, the Sr-HAP adsorbent could effectively remove Co(II) in a wide pH range of 3-8. Increasing temperature was conducive to the adsorption, and the maximum Co(II) adsorption capacity by Sr-HAP reached 48.467 mg/g at 45 °C. The adsorption of Co(II) followed the pseudo-second-order kinetic model, indicating that the Co(II) adsorption by Sr-HAP was attributed mainly to chemisorption. The isothermal adsorption results showed that at lower Co(II) equilibrium concentration, the Langmuir model fitted the data better than the Freundlich model but opposite at higher Co(II) equilibrium concentration. Therefore, the adsorption of Co(II) was a process from monolayer adsorption to multilayer adsorption with the increase of the Co(II) equilibrium concentration. The diffusion analysis of Co(II) to Sr-HAP indicated that the internal diffusion and surface adsorption were the rate-controlled steps of Co(II) adsorption. Thermodynamic study demonstrated that the Co(II) adsorption process was spontaneous and endothermic. The mechanism study revealed that in addition to chemisorption, Sr-HAP also removed Co(II) ions from water via ion exchange and surface complexation.

Anisamide-conjugated hairpin antisense oligonucleotides prodrug co-delivering doxorubicin exhibited enhanced anticancer efficacy.

Antisense oligonucleotides (ASONs)-based therapeutics offers tremendous promise for the treatment of diverse diseases. However, there is still a need to develop ASONs with enhanced stability against enzymes, improved drug delivery, and enhanced biological potency. In this study, we propose a novel anisamide (AA)-conjugated hairpin oligonucleotide prodrug loading with chemotherapeutic agent (doxorubicin, DOX) (AA-loop-ASON/DOX) for oncotherapy. Results indicated that the introduction of a hairpin conformation and AA ligand in prodrug significantly improved the stability against enzymatic hydrolysis, as well as the cellar uptake of ASONs and DOX. The incorporation of disulfide bonds could trigger mechanical opening, resulting in the release of ASON and DOX in response to the intracellular glutathione (GSH) in tumors. Moreover, the composite of DOX-loading ASONs prodrug exhibited a robust and selective inhibition of tumor cell proliferation. This paper introduces a novel design concept for nucleic acid-based therapeutics, aiming to enhance the delivery of drug and improve biological effectiveness.

Integrating target-responsive microfluidic-based biosensing chip with smartphone for simultaneous quantification of multiple fluoroquinolones.

The presence of fluoroquinolone (FQs) antibiotic residues in the food and environment has become a significant concern for human health and ecosystems. In this study, the background-free properties of upconversion nanoparticles (UCNPs), the high specificity of the target aptamer (Apt), and the high quenching properties of graphene oxide (GO) were integrated into a microfluidic-based fluorescence biosensing chip (MFBC). Interestingly, the microfluidic channels of the MFBC were prepared by laser-printing technology without the need for complex preparation processes and additional specialized equipment. The target-responsive fluorescence biosensing probes loaded on the MFBC were prepared by self-assembly of the UCNPs-Apt complex with GO based on π-π stacking interactions, which can be used for the detection of the two FQs on a large scale without the need for multi-step manipulations and reactions, resulting in excellent multiplexed, automated and simultaneous sensing capabilities with detection limits as low as 1.84 ng/mL (enrofloxacin) and 2.22 ng/mL (ciprofloxacin). In addition, the MFBC was integrated with a smartphone into a portable device to enable the analysis of a wide range of FQs in the field. This research provides a simple-to-prepare biosensing chip with great potential for field applications and large-scale screening of FQs residues in the food and environment.

The Changes of Blood and CSF Ion Levels in Depressed Patients: a Systematic Review and Meta-analysis.

Micronutrient deficiencies and excesses are closely related to developing and treating depression. Traditional and effective antidepressants include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and lithium. There is no consensus on the fluctuation of zinc (Zn2+), magnesium (Mg2+), calcium (Ca2+), copper (Cu2+), iron (Fe2+), and manganese (Mn2+) ion levels in depressed individuals before and after therapy. In order to determine whether there were changes in blood and cerebrospinal fluid (CSF) levels of these ions in depressed patients compared with healthy controls and depressed patients treated with TCAs, SSRIs, or lithium, we applied a systematic review and meta-analysis. Using the Stata 17.0 software, we performed a systematic review and meta-analysis of the changes in ion levels in human samples from healthy controls, depressive patients, and patients treated with TCAs, SSRIs, and lithium, respectively. By searching the PubMed, EMBASE, Google Scholar, Web of Science, China National Knowledge Infrastructure (CNKI), and WAN FANG databases, 75 published analyzable papers were chosen. In the blood, the levels of Zn2+ and Mg2+ in depressed patients had decreased while the Ca2+ and Cu2+ levels had increased compared to healthy controls, Fe2+ and Mn2+ levels have not significantly changed. After treatment with SSRIs, the levels of Zn2+ and Ca2+ in depressed patients increased while Cu2+ levels decreased. Mg2+ and Ca2+ levels were increased in depressed patients after Lithium treatment. The findings of the meta-analysis revealed that micronutrient levels were closely associated with the onset of depression and prompted more research into the underlying mechanisms as well as the pathophysiological and therapeutic implications.

Mechanism of scutellarin inhibition of astrocyte activation to type A1 after ischemic stroke.

OBJECTIVE: The aim of this study was to investigate the effects of scutellarin on the activation of astrocytes into the A1 type following cerebral ischemia and to explore the underlying mechanism. METHODS: In vivo, a mouse middle cerebral artery wire embolism model was established to observe the regulation of astrocyte activation to A1 type by scutellarin, and the effects on neurological function and brain infarct volume. In vitro, primary astrocytes were cultured to establish an oxygen-glucose deprivation model, and the mRNA and protein expression of C3, a specific marker of A1-type astrocytes pretreated with scutellarin, were examined. The neurons were cultured in vitro to detect the toxic effects of ischemia-hypoxia-activated A1 astrocyte secretion products on neurons, and to observe whether scutellarin could reduce the neurotoxicity of A1 astrocytes. To validate the signaling pathway-related proteins regulated by scutellarin on C3 expression in astrocytes. RESULTS: The results showed that scutellarin treatment reduced the volume of cerebral infarcts and attenuated neurological deficits in mice caused by middle cerebral artery embolism. Immunofluorescence and Western blot showed that treatment with scutellarin down-regulated middle cerebral artery embolism and OGD/R up-regulated A1-type astrocyte marker C3. The secretory products of ischemia-hypoxia-activated A1-type astrocytes were toxic to neurons and induced an increase in neuronal apoptosis, and astrocytes treated with scutellarin reduced the toxic effects on neurons. Further study revealed that scutellarin inhibited the activation of NF-κB signaling pathway and thus inhibited the activation of astrocytes to A1 type.

Urbanization and weather dynamics co-dominated the spatial-temporal variation in pCO2 and CO2 fluxes in small montanic rivers draining diverse landscapes.

Rivers have been widely reported as important CO2 emitters to the atmosphere. Rapid urbanization has a profound impact on the carbon biogeochemical cycle of rivers, leading to enhanced riverine CO2 evasions. However, it is still unclear whether the spatial-temporal patterns of CO2 emissions in the rivers draining diverse landscapes dominated by urbanization were stable, especially in mountainous areas. This study carried out a two-year investigation of water environmental hydrochemistry in three small mountainous rivers draining urban, suburban and rural landscapes in southwestern China, and CO2 partial pressure (pCO2) and fluxes (fCO2) in surface water were measured using headspace equilibrium method and classical thin boundary layer model. The average pCO2 and fCO2 in the highly urbanized river were of 4783.6 µatm and 700.0 mmol m-2 d-1, conspicuously higher than those in the rural river (1525.9 µatm and 123.2 mmol m-2 d-1), and the suburban river presented a moderate level (3114.2 µatm and 261.2 mmol m-2 d-1). It provided even clearer evidence that watershed urbanization could remarkably enhance riverine CO2 emissions. More importantly, the three rivers presented different longitudinal variations in pCO2, implying diversified spatial patterns of riverine CO2 emissions as a result of urbanization. The urban land can explain 49.6-69.1% of the total spatial variation in pCO2 at the reach scale, indicating that urban land distribution indirectly dominated the longitudinal pattern of riverine pCO2 and fCO2. pCO2 and fCO2 in the three rivers showed similar temporal variability with higher warm-rainy seasons and lower dry seasons, which are significantly controlled by weather dynamics, including monthly temperature and precipitation, but seem to be impervious to watershed urbanization. High temperature-stimulated microorganisms metabolism and riched-CO2 runoff input lead much higher pCO2 in warm-rainy seasons. However, it showed more sensitivity of pCO2 to monthly weather dynamics in urbanized rivers than that in rural rivers, and warm-rainy seasons showed hot moments of CO2 evasion for urban rivers. TOC, DOC, TN, pH and DO were the main controls on pCO2 in the urban and suburban rivers, while only pH and DO were connected with pCO2 in the rural rivers. This indicated differential controls and regulatory processes of pCO2 in the rivers draining diverse landscapes. Furthermore, it suggested that pCO2 calculated by the pH-total alkalinity method would obviously overestimate pCO2 in urban polluted rivers due to the inevitable influence of non-carbonate alkalinity, and thus, a relatively conservative headspace method should be recommended. We highlighted that urbanization and weather dynamics co-dominated the multiformity and uncertainty in spatial-temporal patterns of riverine CO2 evasions, which should be considered when modeling CO2 dynamics in urbanized rivers.

CX3CR1 mediates motor dysfunction in mice through 5-HTR2a.

CX3CR1 knockout could induce motor dysfunction in several neurological disease models mainly through regulating microglia's function. While CX3CR1 was expressed on neurons in a few reports, whether neuronal CX3CR1 could affect the function of neurons and mediate motor dysfunction under physiological conditions is unknown. To elucidate the roles of neuronal CX3CR1 on motor dysfunction, CX3CR1 knockout mice were created. Rotarod test and Open field test found that the CX3CR1-/- mice's motor capacity was reduced. Immunofluorescence staining detected the expression of CX3CR1 in neurons both in vivo and in vitro. Immunohistochemistry and West blot found that knockout of CX3CR1 did not affect the neurons' number in both spinal cord and brain of mice. While inhibiting the function of CX3CR1 by AZD8797 could decrease the expression of 5-Hydroxytryptamine receptor(5-HTR2a), which involved in the regulation of motor function. Further investigation revealed that CX3CR1 regulated the expression of HTR2a through the NF-κB pathway. For the first time, we reported that neuronal CXCR1 mediates motor dysfunction. Our results suggest that modulating CXCR1 activity offers a novel therapeutic strategy for motor dysfunction.

Water-stable hydrophilic metal organic framework composite for the recognition of N-glycopeptides during diabetes progression by mass spectrometry.

A hydrophilic Al-MOFs composite was prepared using cheap and available reagents in water via a suitable large-scale production, an economical and environment-friendly method for capturing N-glycopeptides. The prepared Al-MOFs composite with high hydrolytically stable and hydrophilic 1D channels exhibits an ultralow detection limit (0.5 fmol/µL), and excellent reusability (at least 10 cycles) in the capture of N-glycopeptides from standard bio-samples. Interestingly, the Al-MOFs composite also shows remarkable performance in practical applications, where 300 N-glycopeptides ascribed to 124 glycoproteins were identified in 1 µL human serum and were successfully applied in profiling the differences of N-glycopeptides during diabetes progression. Moreover, 12 specific glycoproteins used as biomarkers to accurately distinguish the progression of diabetes are identified. The present work provides a potential commercial method for large-scale glycoproteomics research in complex clinical samples while offering new guidance for the precise diagnosis of diabetes progression.

Cerebrospinal fluid oligoclonal bands in Chinese patients with multiple sclerosis: the prevalence and its association with clinical features.

Background: Cerebrospinal fluid oligoclonal band (CSF-OCB) is an established biomarker in diagnosing multiple sclerosis (MS), however, there are no nationwide data on CSF-OCB prevalence and its diagnostic performance in Chinese MS patients, especially in the virtue of common standard operation procedure (SOP). Methods: With a consensus SOP and the same isoelectric focusing system, we conducted a nationwide multi-center study on OCB status in consecutively, and recruited 483 MS patients and 880 non-MS patients, including neuro-inflammatory diseases (NID, n = 595) and non-inflammatory neurological diseases (NIND, n=285). Using a standardized case report form (CRF) to collect the clinical, radiological, immunological, and CSF data, we explored the association of CSF-OCB positivity with patient characters and the diagnostic performance of CSF-OCB in Chinese MS patients. Prospective source data collection, and retrospective data acquisition and statistical data analysis were used. Findings: 369 (76.4%) MS patients were OCB-positive, while 109 NID patients (18.3%) and 6 NIND patients (2.1%) were OCB-positive, respectively. Time from symptom onset to diagnosis was significantly shorter in OCB-positive than that in OCB-negative MS patients (13.2 vs 23.7 months, P=0.020). The prevalence of CSF-OCB in Chinese MS patients was significantly higher in high-latitude regions (41°-50°N)(P=0.016), and at high altitudes (>1000m)(P=0.025). The diagnostic performance of CSF-OCB differentiating MS from non-MS patients yielded a sensitivity of 76%, a specificity of 87%. Interpretation: The nationwide prevalence of CSF-OCB was 76.4% in Chinese MS patients, and demonstrated a good diagnostic performance in differentiating MS from other CNS diseases. The CSF-OCB prevalence showed a correlation with high latitude and altitude in Chinese MS patients.

Forsythia suspensa (Thunb.) Vahl extract ameliorates ulcerative colitis via inhibiting NLRP3 inflammasome activation through the TLR4/MyD88/NF-κB pathway.

BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory disease, is caused by abnormal immune system reactions resulting in inflammation and ulcers in the large intestine. Phillygenin (PHI) is a natural compound found in Forsythia suspensa (Thunb.) Vahl, which is known for its antipyretic, anti-inflammatory, antiobesity, and other biological activities. However, the therapeutic role and molecular mechanisms of PHI on UC are still insufficiently researched. METHODS: In this study, dextran sulfate sodium (DSS) and 2.5% 2,4,6-trinitro-Benzenesulfonic acid (TNBS)-induced acute UC were used to investigate the therapeutic effects of PHI. We evaluated the effects of PHI on disease activity index (DAI), body weight, mortality, intestinal mucosal barrier, cytokine secretion, and macrophage infiltration into colon tissue using various techniques such as flow cytometry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), RT-qPCR, and Western blot analysis. RESULTS: Our findings revealed that PHI has therapeutic properties in UC treatment. PHI was able to maintain body weight, reduce DAI and mortality, restore the intestinal mucosal barrier, and inhibit cytokine secretion. Flow cytometry assay and immunofluorescence indicated that PHI reduces macrophage infiltration into colon tissue. Mechanistically, PHI may exert anti-inflammatory effects by downregulating the TLR4/MyD88/NF-κB pathway and inhibiting the activation of NLRP3 inflammasome. CONCLUSION: In conclusion, PHI possesses significant anti-inflammatory properties and is expected to be a potential drug for UC treatment. Our study delves into the underlying mechanisms of PHI therapy and highlights the potential for further research in developing PHI-based treatments for UC.

Physiological and transcriptomic analysis of the mangrove species Kandelia obovata in response to flooding stress.

Flooding stress on mangroves is growing continually with rising sea level. In this study, the physiology and transcriptome of the mangrove species Kandelia obovata under flooding stress were analyzed. With increasing inundation time, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), soluble sugar (SS), soluble protein (SP), and proline (Pro) content declined, while peroxidase (POD) and ascorbate peroxidase (APX) activity rose significantly. According to the KEGG pathway enrichment analysis, upregulated differentially expressed genes (DEGs) were enriched in the plant hormone signaling pathway. Furthermore, MYB44 and MYB108 genes from the MYB transcription factor family and RAP2.12, DREB2B, and ERF4 genes from the AP2/ERF family were up-regulated under flooding conditions. A strong correlation was established between the expression levels of 12 DEGs under flooding stress and RNA sequencing data and was verified by qRT-PCR. These results provide new insights into the molecular mechanism of K. obovata in response to flooding stress.

A dihydro-benzo[4,5]imidazo[1,2-c]quinazoline-based probe with aggregation-induced ratiometric emission for the ratiometric fluorescent detection of peroxynitrite in living cells and zebrafish.

As a significant kind of reactive oxygen species (ROS), peroxynitrite (ONOO-) plays an indispensable role in many physiological and pathological processes. This study aimed to synthesize a novel dihydro-benzo[4,5]imidazo[1,2-c]quinazoline-based probe 1 for detecting ONOO-. In 99.5% H2O solution, probe 1 displayed a distinct aggregation-induced ratiometric emission (AIRE), and would selectively respond toward ONOO-via a ratiometric fluorescent signal, along with a short response time (<30 s) and ultra-sensitivity (LOD = 17.6 nM). Moreover, the probe was applied for monitoring the concentration fluctuations of ONOO- in HeLa cells and zebrafish.

NAD+ exhaustion by CD38 upregulation contributes to blood pressure elevation and vascular damage in hypertension.

Hypertension is characterized by endothelial dysfunction and arterial stiffness, which contribute to the pathogenesis of atherosclerotic cardiovascular diseases. Nicotinamide adenine dinucleotide (NAD+) is an indispensable cofactor in all living cells that is involved in fundamental biological processes. However, in hypertensive patients, alterations in NAD+ levels and their relation with blood pressure (BP) elevation and vascular damage have not yet been studied. Here we reported that hypertensive patients exhibited lower NAD+ levels, as detected by high-performance liquid chromatography-mass spectrometry (HPLC-MS), in both peripheral blood mononuclear cells (PBMCs) and aortas, which was parallel to vascular dysfunction. NAD+ boosting therapy with nicotinamide mononucleotide (NMN) supplement reduced BP and ameliorated vascular dysfunction in hypertensive patients (NCT04903210) and AngII-induced hypertensive mice. Upregulation of CD38 in endothelial cells led to endothelial NAD+ exhaustion by reducing NMN bioavailability. Pro-inflammatory macrophages infiltration and increase in IL-1ß generation derived from pro-inflammatory macrophages resulted in higher CD38 expression by activating JAK1-STAT1 signaling pathway. CD38 KO, CD38 inhibitors treatment, or adeno-associated virus (AAV)-mediated endothelial CD38 knockdown lowered BP and improved vascular dysfunction in AngII-induced hypertensive mice. The present study demonstrated for the first time that endothelial CD38 activation and subsequently accelerated NAD+ degradation due to enhanced macrophage-derived IL-1ß production was responsible for BP elevation and vascular damage in hypertension. NAD+ boosting therapy can be used as a novel therapeutic strategy for the management of hypertensive patients.

The early effects of sleeve gastrectomy on postprandial chylomicron triglycerides during the progression of type 2 diabetes.

BACKGROUND: It remains unclear whether early sleeve gastrectomy (SG) improves postprandial very-low-density lipoprotein (VLDL) as well as chylomicron triglycerides (TGs) in a weight-independent manner in patients with or without type 2 diabetes (DM). Herein we investigated the early effects of SG on postprandial VLDL and chylomicron kinetics. METHODS: A liquid meal test was performed before and after 1 week of SG. The plasma was collected for postprandial triglyceride-rich lipoprotein kinetics analyses, including VLDLs and chylomicrons, isolated by high-speed ultracentrifugation. Lipidomics and metabolomics were used to profile lipid and metabolite compositions of plasma and postprandial chylomicrons. De novo fatty acid synthesis in intestinal epithelial cells treated with chylomicron metabolites was examined using RT-PCR, immunoblotting, and free fatty acid measurement. RESULTS: We found that patients with DM had markedly higher VLDL TGs than patients without DM, and such an increase was still retained after SG. In contrast, SG significantly decreased postprandial chylomicron TGs, but surprisingly, the degree of the reduction in patients with DM was less prominent than in patients without DM, confirmed by untargeted lipidomics analysis. Moreover, 5 unique metabolites potentially linked to de novo fatty acid synthesis from the pathway analysis were discovered by further metabolomic analysis of postprandial chylomicrons from patients with DM who underwent SG and verified by In vitro intestinal epithelial cell culture experiments. CONCLUSIONS: SG in 1 week did not impact postprandial VLDL but decreased chylomicron TGs. Patients with DM keep higher postprandial chylomicron TG concentrations than patients without it after SG, potentially through some unique metabolites that increase intestinal fatty acid synthesis. These results implicate the timing for SG to reach lower intestinal fatty acid synthesis and postprandial chylomicron TG production is prior to the diagnosis of DM to potentially reduce cardiovascular risks.

Design, characterization and biological evaluation of a new chimeric 4A2-5-antisense prodrug combined with chemotherapy.

Issues surrounding rapid degradation and limited therapeutic efficacy still exist in the development of native antisense oligonucleotides (ASONs). In this paper, a novel strategy of chimeric 4A2-5-ASON prodrug combined with chemotherapy for oncotherapy was proposed. The self-assembled hairpin-end prodrug structure provided a DOX loading site, while enhancing stability against nuclease degradation. The disulfide led responsive drug release, and excellent therapeutic effects were achieved by the combined action of RNase H and RNase L recruitment, along with chemotherapy drug Doxorubicin (DOX), both in vitro and in vivo. This work provides evidence for the development of designing nucleic acid drugs with combined mechanisms.

Circulating Neuropeptide Y May Be a Biomarker for Diagnosing Atrial Fibrillation.

INTRODUCTION: Sympathetic nervous system disorder promotes atrial fibrillation (AF), and neuropeptide Y (NPY) is an important neurotransmitter. This study aimed to explore the predictive value of plasma NPY in patients with AF. METHODS: Five hundred seventy-six patients were divided into AF (including paroxysmal and long-standing persistent AF; 360) and sinus rhythm (SR) groups (216). NPY level was detected using enzyme-linked immunosorbent assay, and NPY mRNA expression level was detected using quantitative polymerase chain reaction. Logistic regression was used to analyse the risk factors for AF; the correlations between blood NPY level and age, body mass index (BMI), left ventricular ejection fraction, left atrial diameter (LAD), and European Heart rate Association (EHRA) score in patients with AF were determined. The receiver operating characteristic (ROC) curve was utilised to predict AF. RESULTS: Plasma NPY levels were found to be higher in patients with AF than in patients with SR and in patients with long-standing persistent AF than in patients with paroxysmal AF; blood NPY mRNA levels were higher in the paroxysmal and long-standing persistent AF groups compared to the SR group (p < 0.05). Increased age {odds ratio (OR) = 1.201 (95% confidence interval [CI]: 1.01, 1.427)} and high NPY [OR = 1.239 (95% CI: 1.022, 1.501)] were factors found to affect AF detrimentally. NPY was associated with BMI (r = 0.5856, p < 0.05), LAD (r = 0.4023, p < 0.05), and EHRA score (r = 0.898, p < 0.05). The ROC curve for the predictive value of plasma NPY levels for AF showed an area under the curve (AUC) value of 0.919 (p < 0.05), while that for long-standing persistent AF showed an AUC of 0.784 (p < 0.05). CONCLUSION: Circulating NPY may be a promising molecular biomarker of AF.