Multiomics Analysis Revealed Colorectal Cancer Pathogenesis.

Gut microbiota-derived microbial compounds may link to the pathogenesis of colorectal cancer (CRC). However, the role of the host-microbiome in the incidence and progression of CRC remains elusive. We performed 16S rRNA sequencing, metabolomics, and proteomic studies on samples from 85 CRC patients who underwent colonoscopy examination and found two distinct changed patterns of microbiome in CRC patients. The relative abundances of Catabacter and Mogibacterium continuously increased from intramucosal carcinoma to advanced stages, whereas Clostridium, Anaerostipes, Vibrio, Flavonifractor, Holdemanella, and Hungatella were significantly altered only in intermediate lesions. Fecal metabolomics analysis exhibited consistent increases in bile acids, indoles, and urobilin as well as a decrease in heme. Serum metabolomics uncovered the highest levels of bilin, glycerides, and nucleosides together with the lowest levels of bile acids and amino acids in the stage of intermediate lesions. Three fecal and one serum dipeptides were elevated in the intermediate lesions. Proteomics analysis of colorectal tissues showed that oxidation and autophagy through the PI3K/Akt-mTOR signaling pathway contribute to the development of CRC. Diagnostic analysis showed multiomics features have good predictive capability, with AUC greater than 0.85. Our overall findings revealed new candidate biomarkers for CRC, with potentially significant diagnostic and prognostic capabilities.

Comparing surgical site wound infection after laparoscopic and open radical cystectomies in patients with bladder cancer.

This study comprehensively compared the effects of laparoscopic and open radical cystectomies on postoperative wound infections and complications in patients with bladder cancer. We conducted a systematic search for relevant studies in PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases, from database inception to October 2023. Two researchers independently screened the literature, extracted data, and assessed the quality based on the inclusion and exclusion criteria. Data analysis was performed using Stata 17.0 software. Overall, 16 studies involving 1427 patients with bladder cancer were included. The analysis revealed that, compared with open radical cystectomy, laparoscopic radical cystectomy significantly reduced the incidence of wound infections (odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.23-0.64, p < 0.001) and complications (OR = 0.35, 95%CI: 0.26-0.47, p < 0.001) and significantly shortened the hospital stay duration (standardised mean difference [SMD] = -1.85, 95%CI: -2.34 to -1.36, p < 0.001). Thus, this study determined that laparoscopic radical cystectomy for the treatment of bladder cancer effectively reduced the occurrence of wound infections and complications, and significantly shortened the patient's hospital stay, demonstrating notable therapeutic effectiveness worthy of clinical application.

Advances in encapsulation systems of Antarctic krill oil: From extraction to encapsulation, and future direction.

Antarctic krill oil (AKO) is highly sought after by consumers and the food industry due to its richness in a variety of nutrients and physiological activities. However, current extraction methods are not sufficient to better extract AKO and its nutrients, and AKO is susceptible to lipid oxidation during processing and storage, leading to nutrient loss and the formation of off-flavors and toxic compounds. The development of various extraction methods and encapsulation systems for AKO to improve oil yield, nutritional value, antioxidant capacity, and bioavailability has become a research hotspot. This review summarizes the research progress of AKO from extraction to encapsulation system construction. The AKO extraction mechanism, technical parameters, oil yield and composition of solvent extraction, aqueous enzymatic extraction, supercritical/subcritical extraction, and three-liquid-phase salting-out extraction system are described in detail. The principles, choice of emulsifier/wall materials, preparation methods, advantages and disadvantages of four common encapsulation systems for AKO, namely micro/nanoemulsions, microcapsules, liposomes and nanostructured lipid carriers, are summarized. These four encapsulation systems are characterized by high encapsulation efficiency, low production cost, high bioavailability and high antioxidant capacity. Depending on the unique advantages and conditions of different encapsulation methods, as well as consumer demand for health and nutrition, different products can be developed. However, existing AKO encapsulation systems lack relevant studies on digestive absorption and targeted release, and the single product category of commercially available products limits consumer choice. In conjunction with clinical studies of AKO encapsulation systems, the development of encapsulation systems for special populations should be a future research direction.

Hemodynamics of ventricular-arterial coupling under enhanced external counterpulsation: An optimized dual-source lumped parameter model.

BACKGROUND AND OBJECTIVE: Enhanced external counterpulsation (EECP) is a mechanically assisted circulation technique widely used in the rehabilitation and management of ischemic cardiovascular diseases. It contributes to cardiovascular functions by regulating the afterload of ventricle to improve hemodynamic effects, including increased diastolic blood pressure at aortic root, increased cardiac output and enhanced blood perfusion to multiple organs including coronary circulation. However, the effects of EECP on the coupling of the ventricle and the arterial system, termed ventricular-arterial coupling (VAC), remain elusive. We aimed to investigate the acute effect of EECP on the dynamic interaction between the left ventricle and its afterload of the arterial system from the perspective of ventricular output work. METHODS: A neural network assisted optimization algorithm was proposed to identify the ordinary differential equation (ODE) relation between aortic root blood pressure and flow rate. Based on the optimized order of ODE, a lumped parameter model (LPM) under EECP was developed taking into consideration of the simultaneous action of cardiac and EECP pressure sources. The ventricular output work, in terms of aortic pressure and flow rate cooperated with the LPM, was used to characterize the VAC of ventricle and its afterload. The VAC subjected to the principle of minimal ventricular output work was validated by solving the Euler-Poisson equation of cost function, ultimately determining the waveforms of aortic pressure and flow rate. RESULTS: A third-order ODE can precisely describe the hemodynamic relationship between aortic pressure and flow rate. An optimized dual-source LPM with three energy-storage elements has been constructed, showing the potential in probing VAC under EECP. The LPM simulation results demonstrated that the VAC in terms of aortic pressure and flow rate yielded to the minimal ventricular output work under different EECP pressures. CONCLUSIONS: The ventricular-arterial coupling under EECP is subjected to the minimal ventricular output work, which can serve as a criterion for determining aortic pressure and flow rate. This study provides insight for the understanding of VAC and has the potential in characterizing the performance of the ventricular and arterial system under EECP.

Effect of coffee, tea and alcohol intake on circulating inflammatory cytokines: a two sample-Mendelian randomization study.

BACKGROUND: Despite the abundance of research examining the effects of coffee, tea, and alcohol on inflammatory diseases, there is a notable absence of conclusive evidence regarding their direct causal influence on circulating inflammatory cytokines. Previous studies have primarily concentrated on established cytokines, neglecting the potential impact of beverage consumption on lesser-studied but equally important cytokines. METHODS: Information regarding the consumption of coffee, tea, and alcohol was collected from the UK Biobank, with sample sizes of 428,860, 447,485, and 462,346 individuals, respectively. Data on 41 inflammatory cytokines were obtained from summary statistics of 8293 healthy participants from Finnish cohorts. RESULTS: The consumption of coffee was found to be potentially associated with decreased levels of Macrophage colony-stimulating factor (ß = -0.57, 95% CI -1.06 ~ -0.08; p = 0.022) and Stem cell growth factor beta (ß = -0.64, 95% CI -1.16 ~ -0.12; p = 0.016), as well as an increase in TNF-related apoptosis-inducing ligand (ß = 0.43, 95% CI 0.06 ~ 0.8; p = 0.023) levels. Conversely, tea intake was potentially correlated with a reduction in Interleukin-8 (ß = -0.45, 95% CI -0.9 ~ 0; p = 0.045) levels. Moreover, our results indicated an association between alcohol consumption and decreased levels of Regulated on Activation, Normal T Cell Expressed and Secreted (ß = -0.24, 95% CI -0.48 ~ 0; p = 0.047), as well as an increase in Stem cell factor (ß = 0.17, 95% CI 0.02 ~ 0.31; p = 0.023) and Stromal cell-derived factor-1 alpha (ß = 0.20, 95% CI 0.04 ~ 0.36; p = 0.013). CONCLUSION: Revealing the interactions between beverage consumption and various inflammatory cytokines may lead to the discovery of novel therapeutic targets, thereby facilitating dietary interventions to complement clinical disease treatments.

MS based foodomics: An edge tool integrated metabolomics and proteomics for food science.

Foodomics has become a popular methodology in food science studies. Mass spectrometry (MS) based metabolomics and proteomics analysis played indispensable roles in foodomics research. So far, several methodologies have been developed to detect the metabolites and proteins in diets and consumers, including sample preparation, MS data acquisition, annotation and interpretation. Moreover, multiomics analysis integrated metabolomics and proteomics have received considerable attentions in the field of food safety and nutrition, because of more comprehensive and deeply. In this context, we intended to review the emerging strategies and their applications in MS-based foodomics, as well as future challenges and trends. The principle and application of multiomics were also discussed, such as the optimization of data acquisition, development of analysis algorithm and exploration of systems biology.

Identification and characterization of camptothecin tailoring enzymes in Nothapodytes tomentosa.

Camptothecin is a complex monoterpenoid indole alkaloid with remarkable antitumor activity. Given that two C-10 modified camptothecin derivatives, topotecan and irinotecan, have been approved as potent anticancer agents, there is a critical need for methods to access other aromatic ring-functionalized congeners (e.g., C-9, C-10, etc.). However, contemporary methods for chemical oxidation are generally harsh and low-yielding when applied to the camptothecin scaffold, thereby limiting the development of modified derivatives. Reported herein, we have identified four tailoring enzymes responsible for C-9 modifications of camptothecin from Nothapodytes tomentosa, via metabolomic and transcriptomic analysis. These consist of a cytochrome P450 (NtCPT9H) which catalyzes the regioselective oxidation of camptothecin to 9-hydroxycamptothecin, as well as two methyltransferases (NtOMT1/2, converting 9-hydroxycamptothecin to 9-methoxycamptothecin), and a uridine diphosphate-glycosyltransferase (NtUGT5, decorating 9-hydroxycamptothecin to 9-ß-D-glucosyloxycamptothecin). Importantly, the critical residues that contribute to the specific catalytic activity of NtCPT9H have been elucidated through molecular docking and mutagenesis experiments. This work provides a genetic basis for producing camptothecin derivatives through metabolic engineering. This will hasten the discovery of novel C-9 modified camptothecin derivatives, with profound implications for pharmaceutical manufacture.

Prevention of Hypercholesterolemia with "Liposomes in Microspheres" Composite Carriers: A Promising Approach for Intestinal-Targeted Oral Delivery of Astaxanthin.

Cardiovascular diseases are caused by hypercholesterolemia. Astaxanthin (AST) has been reported to exhibit antioxidant and anti-inflammatory properties. However, its bioavailability is poor because of low solubility and instability. In order to improve the bioavailability of AST, we developed an intestinal-responsive composite carrier termed as "liposomes in micropheres" incorporating N-succinyl-chitosan (NSC)-poly(ethylene glycol) (PEG) liposomes that functionalized by neonatal Fc receptors (FcRn) into hydrogels of sodium alginate (SA) and carboxymethyl chitosan (CMCS). In the AST NSC/HSA-PEG liposomes@SA/CMCS microspheres, the AST's encapsulation efficiency (EE) was 96.26% (w/w) and its loading capacity (LC) was 6.47% (w/w). AST NSC/HSA-PEG liposomes had stability in the gastric conditions and achieved long-term release of AST in intestinal conditions. Then, AST NSC/HSA-PEG liposomes@SA/CMCS bind to intestinal epithelial cell targets by the neonatal Fc receptor. In vitro permeation studies show that there was a 4-fold increase of AST NSC/HSA-PEG liposomes@SA/CMCS in AST permeation across the intestinal epithelium. Subsequent in vivo experiments demonstrated that the composite carrier exhibited a remarkable mucoadhesive capacity, allowing for extended intestinal retention of up to 12 h, and it displayed deep penetration through the mucus layer, efficiently entering the intestinal villi epithelial cells, and enhancing the absorption of AST and its bioavailability in vivo. And oral administration of AST NSC/HSA-PEG liposomes@SA/CMCS could effectively prevent hypercholesterolemia caused by a high-fat, high-cholesterol diet (HFHCD). These advancements highlight the potential of NSC/HSA-PEG liposomes@SA/CMCS composite carriers for targeted and oral uptake of hydrophobic bioactives.

Preoperative neutrophil-to-lymphocyte ratio predicts symptomatic anastomotic leakage in elderly colon cancer patients: Multicenter propensity score-matched analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a composite inflammatory biomarker, is associated with the prognosis in patients with colorectal tumors. However, whether the NLR can be used as a predictor of symptomatic postoperative anastomotic leakage (AL) in elderly patients with colon cancer is unclear. AIM: To assess the role of the NLR in predicting the occurrence of symptomatic AL after surgery in elderly patients with colon cancer. METHODS: Data from elderly colon cancer patients who underwent elective radical colectomy with anastomosis at three centers between 2018 and 2022 were retrospectively analyzed. Receiver operating characteristic curve analysis was performed to determine the best predictive cutoff value for the NLR. Twenty-two covariates were matched using a 1:1 propensity score matching method, and univariate and multivariate logistic regression analyses were used to determine risk factors for the development of postoperative AL. RESULTS: Of the 577 patients included, 36 (6.2%) had symptomatic AL. The optimal cutoff value of the NLR for predicting AL was 2.66. After propensity score matching, the incidence of AL was significantly greater in the ≥ 2.66 NLR subgroup than in the < 2.66 NLR subgroup (11.5% vs 2.5%; P = 0.012). Univariate logistic regression analysis revealed statistically significant correlations between blood transfusion intraoperatively and within 2 d postoperatively, preoperative albumin concentration, preoperative prognostic nutritional index, and preoperative NLR and AL occurrence (P < 0.05); multivariate logistic regression analysis revealed that an NLR ≥ 2.66 [odds ratio (OR) = 5.51; 95% confidence interval (CI): 1.50-20.26; P = 0.010] and blood transfusion intraoperatively and within 2 d postoperatively (OR = 2.52; 95%CI: 0.88-7.25; P = 0.049) were risk factors for the occurrence of symptomatic AL. CONCLUSION: A preoperative NLR ≥ 2.66 and blood transfusion intraoperatively and within 2 d postoperatively are associated with a higher incidence of postoperative symptomatic AL in elderly patients with colon cancer. The preoperative NLR has predictive value for postoperative symptomatic AL after elective surgery in elderly patients with colon cancer.

Effect of beta-cypermethrin on the reproductive capacity of female mice in advanced age.

The aim of the present study was to investigate whether exposure to pesticides beta-cypermethrin (ß-CYP) harms the reproductive capacity of advanced-age female mice. The results evidenced that peri-implantation ß-CYP exposure significantly reduced the number of fetuses per advanced-age female in the first litter, and the number and weight of implantation sites. The levels of decidualization markers were significantly reduced in ß-CYP-administered advanced-age mice. Lower expression of Pcna, Cdk6, Foxo1, Ki67, and p62 protein and mRNA was found in the decidua of ß-CYP-treated advanced-age mice. The levels of Bax, cleaved caspase-3, Lc3a/b, Atg, mTOR, and p-mTOR protein, and the ratio of p-mTOR/mTOR protein expression were clearly downregulated by peri-implantation ß-CYP exposure. These results indicated that peri-implantation ß-CYP exposure may elevate the decline in reproductive capacity of early pregnant mice in advanced age.

Melatonin restores DNFB-induced dysbiosis of skin microbiota in a mouse model of atopic dermatitis.

BACKGROUND: The epidermic microbiota plays crucial roles in the pathogenesis of atopic dermatitis (AD), a common inflammatory skin disease. Melatonin (MLT) has been shown to ameliorate skin damage in AD patients, yet the underlying mechanism is unclear. METHODS: Using 2,4-dinitrofluorobenzene (DNFB) to induce an AD model, MLT intervention was applied for 14 days to observe its pharmaceutical effect. Skin lesions were observed using HE staining, toluidine blue staining and electron microscopy. Dermal proinflammatory factor (IL-4 and IL-13) and intestinal barrier indices (ZO1 and Occludin) were assessed by immunohistochemistry and RT-qPCR, respectively. The dysbiotic microbiota was analyzed using 16S rRNA sequencing. RESULTS: MLT significantly improved skin lesion size; inflammatory status (mast cells, IgE, IL-4, and IL-13); and the imbalance of the epidermal microbiota in AD mice. Notably, Staphylococcus aureus is the key bacterium associated with dysbiosis of the epidermal microbiota and may be involved in the fine modulation of mast cells, IL-4, IL-13 and IgE. Correlation analysis between AD and the gut revealed that intestinal dysbiosis occurred earlier than that of the pathological structure in the gut. CONCLUSION: Melatonin reverses DNFB-induced skin damage and epidermal dysbiosis, especially in S. aureus.

Chromosome level genome assembly of endangered medicinal plant Anisodus tanguticus.

Anisodus tanguticus is a medicinal herb that belongs to the Anisodus genus of the Solanaceae family. This endangered herb is mainly distributed in Qinghai-Tibet Plateau. In this study, we combined the Illumina short-read, Nanopore long-read and high-throughput chromosome conformation capture (Hi-C) sequencing technologies to de novo assemble the A. tanguticus genome. A high-quality chromosomal-level genome assembly was obtained with a genome size of 1.26 Gb and a contig N50 of 25.07 Mb. Of the draft genome sequences, 97.47% were anchored to 24 pseudochromosomes with a scaffold N50 of 51.28 Mb. In addition, 842.14 Mb of transposable elements occupying 66.70% of the genome assembly were identified and 44,252 protein-coding genes were predicted. The genome assembly of A. tanguticus will provide genetic repertoire to understand the adaptation strategy of Anisodus species in the plateau, which will further promote the conservation of endangered A. tanguticus resources.

IP3R2-mediated Ca2+ release promotes LPS-induced cardiomyocyte pyroptosis via the activation of NLRP3/Caspase-1/GSDMD pathway.

Pyroptosis plays a crucial role in sepsis, and the abnormal handling of myocyte calcium (Ca2+) has been associated with cardiomyocyte pyroptosis. Specifically, the inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is a Ca2+ release channel in the endoplasmic reticulum (ER). However, the specific role of IP3R2 in sepsis-induced cardiomyopathy (SIC) has not yet been determined. Thus, this study aimed to investigate the underlying mechanism by which IP3R2 channel-mediated Ca2+ signaling contributes to lipopolysaccharide (LPS)-induced cardiac pyroptosis. The SIC model was established in rats by intraperitoneal injection of LPS (10 mg/kg). Cardiac dysfunction was assessed using echocardiography, and the protein expression of relevant signaling pathways was analyzed using ELISA, RT-qPCR, and western blot. Small interfering RNAs (siRNA) and an inhibitor were used to explore the role of IP3R2 in neonatal rat cardiomyocytes (NRCMs) stimulated by LPS in vitro. LPS-induced NLRP3 overexpression and GSDMD-mediated pyroptosis in the rats' heart. Treatment with the NLRP3 inhibitor MCC950 alleviated LPS-induced cardiomyocyte pyroptosis. Furthermore, LPS increased ATP-induced intracellular Ca2+ release and IP3R2 expression in NRCMs. Inhibiting IP3R activity with xestospongin C (XeC) or knocking down IP3R2 reversed LPS-induced intracellular Ca2+ release. Additionally, inhibiting IP3R2 reversed LPS-induced pyroptosis by suppressing the NLRP3/Caspase-1/GSDMD pathway. We also found that ER stress and IP3R2-mediated Ca2+ release mutually regulated each other, contributing to cardiomyocyte pyroptosis. IP3R2 promotes NLRP3-mediated pyroptosis by regulating ER Ca2+ release, and the mutual regulation of IP3R2 and ER stress further promotes LPS-induced pyroptosis in cardiomyocytes.

Correlation between white blood cell count and intestinal resection in patients with acute mesenteric vein thrombosis.

OBJECTIVE: Acute mesenteric vein thrombosis (AMVT) is an acute abdominal disease with onset, rapid progression, and extensive intestinal necrosis that requires immediate surgical resection. The purpose of this study was to determine the risk factors for nosocomial intestinal resection in patients with AMVT. METHODS: We retrospectively analysed 64 patients with AMVT diagnosed by CTA at the Affiliated Hospital of Kunming University of Science and Technology from January 2013 to December 2021. We compared patients who underwent intestinal resection (42 patients) with those who did not undergo intestinal resection (22 patients). The area under the ROC curve was evaluated, and a forest map was drawn. RESULTS: Among the 64 patients, 6 (9.38%) had a fever, 60 (93.75%) had abdominal pain, 9 (14.06%) had a history of diabetes, 8 (12.5%) had a history of deep vein thrombosis (DVT), and 25 (39.06%) had ascites suggested by B ultrasound or CT after admission. The mean age of all patients was 49.86 ± 16.25 years. The mean age of the patients in the enterectomy group was 47.71 ± 16.20 years. The mean age of the patients in the conservative treatment group (without enterectomy) was 53.95 ± 15.90 years. In the univariate analysis, there were statistically significant differences in leukocyte count (P = 0.003), neutrophil count (P = 0.001), AST (P = 0.048), total bilirubin (P = 0.047), fibrinogen (P = 0.022) and DD2 (P = 0.024) between the two groups. The multivariate logistic regression analysis showed that admission white blood cell count (OR = 1.153, 95% CI: 1.039-1.280, P = 0.007) was an independent risk factor for intestinal resection in patients with AMVT. The ROC curve showed that the white blood cell count (AUC = 0.759 95% CI: 0.620-0.897; P = 0.001; optimal threshold: 7.815; sensitivity: 0.881; specificity: 0.636) had good predictive value for emergency enterectomy for AMVT. CONCLUSIONS: Among patients with AMVT, patients with a higher white blood cell count at admission were more likely to have intestinal necrosis and require emergency enterectomy. This study is helpful for clinicians to accurately determine whether emergency intestinal resection is needed in patients with AMVT after admission, prevent further intestinal necrosis, and improve the prognosis of patients.

The chemical and biological characteristics of fatty acid esters of hydroxyl fatty acids.

With the continuous advancements in detection methods and the exploration of unknown substances, an increasing number of bioactive compounds are being discovered. Fatty acid esters of hydroxyl fatty acids (FAHFAs), a class of endogenous lipids found in 2014, exhibit various physiological activities, such as improving glucose tolerance and insulin sensitivity, stimulating insulin secretion, and demonstrating broad anti-inflammatory effects. Moreover, some FAHFAs are closely linked to intestinal health and can serve as potential biomarkers for gut health. Various FAHFAs have been observed in food, including palmitic acid esters of hydroxy stearic acids (PAHSA), oleic acid esters of hydroxy stearic acids (OAHSA), linoleic acid esters of hydroxy linoleic acid (LAHLA). As a type of lipid regularly consumed in the daily diet, it is highly important to ascertain the types and quantities of FAHFAs present in the diet. This article, based on existing research, provides a review of the analysis methods for FAHFAs, particularly focusing on the separation of chiral isomers. It also summarizes the sources and contents of dietary FAHFAs, emphasizing their bioavailability and impact on the gut. Understanding the beneficial effects of these lipids in the diet can serve as a valuable reference for the development of specific functional foods.

Multiomics analysis revealed the mechanism of the anti-diabetic effect of Salecan.

Salecan, a natural ß-glucan compromising nine residues connected by ß-(1 â†’ 3)/α-(1 â†’ 3) glycosidic bonds, is one of the newly approved food ingredients. Salecan has multiple health-improving effects, yet its mechanism against Type 2 diabetes mellitus (T2DM) remains poorly understood. In this study, the hypoglycemic effect and underlying mechanism of Salecan intervention on STZ-induced diabetic model mice were investigated. After 8 weeks of gavage, Salecan attenuated insulin resistance and repaired pancreatic ß cells in a dose-dependent manner. In addition, Salecan supplement remodel the structure of the gut microbiota and altered the level of intestinal metabolites. Serum metabolites, especially unsaturated fatty acids, were also affected significantly. In addition, tight junction proteins in the colon and autophagy-related proteins in the pancreas were upregulated. Multiomics analysis indicated that Lactobacillus johnsonii, Muribaculaceae, and Lachnoclostridium were highly associated with fatty acid esters of hydroxy fatty acids (FAHFA) levels in the colon, accordingly enhancing arachidonic acid and linoleic acid in serum, and promoting GLP-1 release in the intestine and insulin secretion in the pancreas, thus relieving insulin resistance and exhibiting hypoglycemic effects. These findings provide a novel understanding of the anti-diabetic effect of Salecan in mice from a molecular perspective, paving the way for the wide use of Salecan.

Two Unprecedented Germanoniobate Frameworks Based on High-Nuclearity Peanut-Shaped {Ge12Nb38} Clusters.

By variation of the amount of GeO2, two organic-inorganic hybrid germanoniobate frameworks with 6-connected pcu and 10-connected bct topologies were constructed from peanut-shaped {α-Ge12Nb38} and {ß-Ge12Nb38} clusters, respectively. The {α-Ge12Nb38} and {ß-Ge12Nb38} clusters contain the most Ge centers of germanoniobates reported so far. The compounds exhibit proton conduction properties with a conductivity of 3.04 × 10-4 S·cm-3 for 1 and 1.62 × 10-4 S·cm-3 for 2 at 85 °C and 98% RH. The water vapor adsorption capacities for 1 and 2 are 5.86 and 4.40 mmol·g-1, respectively.

Biomimetic nanodecoys deliver cholesterol-modified heteroduplex oligonucleotide to target dopaminergic neurons for the treatment of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) aggregates called Lewy bodies leading to the gradual loss of dopaminergic (DA) neurons in the substantia nigra. Although α-syn expression can be attenuated by antisense oligonucleotides (ASOs) and heteroduplex oligonucleotide (HDO) by intracerebroventricular (ICV) injection, the challenge to peripheral targeted delivery of oligonucleotide safely and effectively into DA neurons remains unresolved. Here, we designed a new DNA/DNA double-stranded (complementary DNA, coDNA) molecule with cholesterol conjugation (Chol-HDO (coDNA)) based on an α-syn-ASO sequence and evaluated its silence efficiency. Further, Chol-HDO@LMNPs, Chol-HDO-loaded, cerebrovascular endothelial cell membrane with DSPE-PEG2000-levodopa modification (L-DOPA-CECm)-coated nanoparticles (NPs), were developed for the targeted treatment of PD by tail intravenous injection. CECm facilitated the blood-brain barrier (BBB) penetration of NPs, together with cholesterol escaped from reticuloendothelial system uptake, as well as L-DOPA was decarboxylated into dopamine which promoted the NPs toward the PD site for DA neuron regeneration. The behavioral tests demonstrated that the nanodecoys improved the efficacy of HDO on PD mice. These findings provide insights into the development of biomimetic nanodecoys loading HDO for precise therapy of PD. STATEMENT OF SIGNIFICANCE: The accumulation of α-synuclein (α-syn) aggregates is a hallmark of PD. Our previous study designed a specific antisense oligonucleotide (ASO) targeting human SNCA, but the traumatic intracerebroventricular (ICV) is not conducive to clinical application. Here, we further optimize the ASO by creating a DNA/DNA double-stranded molecule with cholesterol-conjugated, named Chol-HDO (coDNA), and develop a DA-targeted biomimetic nanodecoy Chol-HDO@LMNPs by engineering cerebrovascular endothelial cells membranes (CECm) with DSPE-PEG2000 and L-DOPA. The in vivo results demonstrated that tail vein injection of Chol-HDO@LMNPs could target DA neurons in the brain and ameliorate motor deficits in a PD mouse model. This investigation provides a promising peripheral delivery platform of L-DOPA-CECm nanodecoy loaded with a new Chol-HDO (coDNA) targeting DA neurons in PD therapy.

Development and application of mass spectrometric molecular networking for analyzing the ingredients of areca nut.

Areca nut (Areca catechu L.) is commonly consumed as a chewing food in the Asian region. However, the investigations into the components of areca nut are limited. In this study, we have developed an approach that combines mass spectrometry with feature-based molecular network to explore the chemical characteristics of the areca nut. In comparison to the conventional method, this technique demonstrates a superior capability in annotating unknown compounds present in areca nut. We annotated a total of 52 compounds, including one potential previously unreported alkaloid, one carbohydrate, and one phenol and confirmed the presence of 7 of them by comparing with commercial standards. The validated method was used to evaluate chemical features of areca nut at different growth stages, annotating 25 compounds as potential biomarkers for distinguishing areca nut growth stages. Therefore, this approach offers a rapid and accurate method for the component analysis of areca nut.

SpecLipIDA: a pseudotargeted lipidomics approach for polyunsaturated fatty acids in milk.

Polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), play an important role in the nutritional value of milk lipids. However, a comprehensive analysis of PUFAs and their esters in milk is still scarce. In this study, we developed a novel pseudotargeted lipidomics approach, named SpecLipIDA, for determining PUFA lipids in milk. Triglycerides (TGs) and phospholipids (PLs) were separated using NH2 cartridges, and mass spectrometry data in the information-dependent acquisition (IDA) mode were preprocessed by MS-DIAL, leading to improved identification in subsequent targeted analysis. The target matching algorithm, based on specific lipid cleavage patterns, demonstrated enhanced identification of PUFA lipids compared to the lipid annotations provided by MS-DIAL and GNPS. The approach was applied to identify PUFA lipids in various milk samples, resulting in the detection of a total of 115 PUFA lipids. The results revealed distinct differences in PUFA lipids among different samples, with 44 PUFA lipids significantly contributing to these differences. Our study indicated that SpecLipIDA is an efficient method for rapidly and specifically screening PUFA lipids.