A ß-Galactosidase-Activated Fluorogenic Reporter for the Detection of Gastric Cancer In Vivo and in Urine.

Although gastric cancer (GC) is one of the most frequent malignant tumors in the digestive tract with high morbidity and mortality, it remains a diagnostic dilemma due to its reliance on invasive biopsy or insensitive assays. Herein, we report a fluorescent gastric cancer reporter (FGCR) with activatable near-infrared fluorescence (NIRF) signals and high renal-clearance efficiency for the detection of orthotopic GC in a murine model via real-time imaging and remote urinalysis. In the presence of gastric-tumor-associated ß-galactosidase (ß-Gal), FGCR can be fluorescently activated for in vivo NIRF imaging. Relying on its high renal-clearance efficiency (∼95% ID), it can be rapidly excreted through kidneys to urine for the ultrasensitive detection of tumors with a diameter down to ∼2.1 mm and for assessing the prognosis of oxaliplatin-based chemotherapy. This study not only provides a new approach for noninvasive auxiliary diagnosis and prognosis of GC but also provides guidelines for the development of fluorescence probes for cancer diagnosis.

Antibacterial activity and mechanism of cell-free supernatants of Lacticaseibacillus paracasei against Propionibacterium acnes.

Propionibacterium acnes (P. acnes) is an anaerobic and gram-positive bacterium involved in the pathogenesis and inflammation of acne vulgaris. This study particularly focuses on the antimicrobial effect of Lacticaseibacillus paracasei LPH01 against P. acnes, a bacterium that causes acne vulgaris. Fifty-seven Lactobacillus strains were tested for their ability to inhibit P. acnes growth employing the Oxford Cup and double dilution methods. The cell-free supernatant (CFS) of L. paracasei LPH01 demonstrated a strong inhibitory effect, with an inhibition zone diameter of 24.65 ± 0.27 mm and a minimum inhibitory concentration of 12.5 mg/mL. Among the CFS, the fraction over 10 kDa (CFS-10) revealed the best antibacterial effect. Confocal laser scanning microscopes and flow cytometry showed that CFS-10 could reduce cell metabolic activity and cell viability and destroy the integrity and permeability of the cell membrane. A scanning electron microscope revealed that bacterial cells exhibited obvious morphological and ultrastructural changes, which further confirmed the damage of CFS-10 to the cell membrane and cell wall. Findings demonstrated that CFS-10 inhibited the conversion of triglycerides, decreased the production of free fatty acids, and down-regulated the extracellular expression of the lipase gene. This study provides a theoretical basis for the metabolite of L. paracasei LPH01 as a potential antibiotic alternative in cosmeceutical skincare products.

Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Transfer learning-based attenuation correction for static and dynamic cardiac PET using a generative adversarial network.

PURPOSE: The goal of this work is to demonstrate the feasibility of directly generating attenuation-corrected PET images from non-attenuation-corrected (NAC) PET images for both rest and stress-state static or dynamic [13N]ammonia MP PET based on a generative adversarial network. METHODS: We recruited 60 subjects for rest-only scans and 14 subjects for rest-stress scans, all of whom underwent [13N]ammonia cardiac PET/CT examinations to acquire static and dynamic frames with both 3D NAC and CT-based AC (CTAC) PET images. We developed a 3D pix2pix deep learning AC (DLAC) framework via a U-net + ResNet-based generator and a convolutional neural network-based discriminator. Paired static or dynamic NAC and CTAC PET images from 60 rest-only subjects were used as network inputs and labels for static (S-DLAC) and dynamic (D-DLAC) training, respectively. The pre-trained S-DLAC network was then fine-tuned by paired dynamic NAC and CTAC PET frames of 60 rest-only subjects to derive an improved D-DLAC-FT for dynamic PET images. The 14 rest-stress subjects were used as an internal testing dataset and separately tested on different network models without training. The proposed methods were evaluated using visual quality and quantitative metrics. RESULTS: The proposed S-DLAC, D-DLAC, and D-DLAC-FT methods were consistent with clinical CTAC in terms of various images and quantitative metrics. The S-DLAC (slope = 0.9423, R2 = 0.947) showed a higher correlation with the reference static CTAC as compared to static NAC (slope = 0.0992, R2 = 0.654). D-DLAC-FT yielded lower myocardial blood flow (MBF) errors in the whole left ventricular myocardium than D-DLAC, but with no significant difference, both for the 60 rest-state subjects (6.63 ± 5.05% vs. 7.00 ± 6.84%, p = 0.7593) and the 14 stress-state subjects (1.97 ± 2.28% vs. 3.21 ± 3.89%, p = 0.8595). CONCLUSION: The proposed S-DLAC, D-DLAC, and D-DLAC-FT methods achieve comparable performance with clinical CTAC. Transfer learning shows promising potential for dynamic MP PET.

Fabrication of a novel polyurethane foam-alginate-zeolite hydrogel and subsequent KSND bacteria encapsulation: evidence of accelerated biofilm colonization and enhanced nitrogen removal efficiency.

Biofilms are used widely to remove nitrogen from wastewater; however, most biofilm carriers (i.e. polyurethane foam, PUF) are hydrophobic organic materials with millimetre-scale apertures, ineffective attachment, and unstable colonization of microorganisms. To address these limitations, hydrophilic sodium alginate (SA) mixed with zeolite powder (Zeo) was cross-linked in PUF to form a micro-scale hydrogel (PAS) with a well-organized and reticular cellular structure. Scanning electron microscopy revealed that immobilized cells were entrapped in the interior of hydrogel filaments and rapidly formed a stable biofilm on the surface. The biofilm generated was 10.3-fold greater than the film developed on PUF. Kinetics and isotherm studies revealed that the as-developed carrier, because of the presence of Zeo, effectively improved the adsorption of NH4+-N by 53%. The PAS carrier achieved total nitrogen removal in excess of 86% for low carbon-to-nitrogen ratio wastewater treated for 30 d, indicating that this novel modification-encapsulation technology has potential for wastewater treatment.

Inhibitors against Two PDZ Domains of MDA-9 Suppressed Migration of Breast Cancer Cells.

Melanoma differentiation-associated gene 9 (MDA-9) is a small adaptor protein with tandem PDZ domains that promotes tumor progression and metastasis in various human cancers. However, it is difficult to develop drug-like small molecules with high affinity due to the narrow groove of the PDZ domains of MDA-9. Herein, we identified four novel hits targeting the PDZ1 and PDZ2 domains of MDA-9, namely PI1A, PI1B, PI2A, and PI2B, using a protein-observed nuclear magnetic resonance (NMR) fragment screening method. We also solved the crystal structure of the MDA-9 PDZ1 domain in complex with PI1B and characterized the binding poses of PDZ1-PI1A and PDZ2-PI2A, guided by transferred paramagnetic relaxation enhancement. The protein-ligand interaction modes were then cross-validated by the mutagenesis of the MDA-9 PDZ domains. Competitive fluorescence polarization experiments demonstrated that PI1A and PI2A blocked the binding of natural substrates to the PDZ1 and PDZ2 domains, respectively. Furthermore, these inhibitors exhibited low cellular toxicity, but suppressed the migration of MDA-MB-231 breast carcinoma cells, which recapitulated the phenotype of MDA-9 knockdown. Our work has paved the way for the development of potent inhibitors using structure-guided fragment ligation in the future.

Chronological and Carbohydrate-Dependent Transformation of Fatty Acids in the Larvae of Black Soldier Fly Following Food Waste Treatment.

Although black soldier fly larvae (BSFL) can convert food waste into insectile fatty acids (FAs), the chronological and diet-dependent transformation of larval FAs has yet to be determined. This study focused on the dynamics of larval FA profiles following food waste treatment and characterized factors that may drive FA composition and bioaccumulation. Larval FA matters peaked on Day 11 as 7.7 ± 0.7% of food waste dry matter, maintained stably from Day 11-19, and decreased slightly from Day 19-21. The BSFL primarily utilized waste carbohydrates for FA bioconversion (Day 0-11) and shifted to waste FAs (Day 7-17) when the carbohydrates were close to depletion. The optimal time window for larvae harvest was Days 17-19, which fulfilled both targets of waste oil removal and larval FA transformation. Larval FAs were dominated by C12:0, followed by C18:2, C18:1, and C16:0. The waste-reducing carbohydrate primarily accounted for larval FA bioaccumulation (r = -0.947, p < 0.001). The increase in diet carbohydrate ratio resulted in the elevation of larval C12:0 yield, which indicated that larval C12:0-FA was primarily biosynthesized from carbohydrates and further transformed from ≥C16 FAs. This study elucidates the bioaccumulation process of larval FAs for food waste treatment and highlights the importance of waste carbohydrates for both the composition and transformation of larval FAs.

Benzophenanthridine Alkaloid Chelerythrine Elicits Necroptosis of Gastric Cancer Cells via Selective Conjugation at the Redox Hyperreactive C-Terminal Sec498 Residue of Cytosolic Selenoprotein Thioredoxin Reductase.

Targeting thioredoxin reductase (TXNRD) with low-weight molecules is emerging as a high-efficacy anti-cancer strategy in chemotherapy. Sanguinarine has been reported to inhibit the activity of TXNRD1, indicating that benzophenanthridine alkaloid is a fascinating chemical entity in the field of TXNRD1 inhibitors. In this study, the inhibition of three benzophenanthridine alkaloids, including chelerythrine, sanguinarine, and nitidine, on recombinant TXNRD1 was investigated, and their anti-cancer mechanisms were revealed using three gastric cancer cell lines. Chelerythrine and sanguinarine are more potent inhibitors of TXNRD1 than nitidine, and the inhibitory effects take place in a dose- and time-dependent manner. Site-directed mutagenesis of TXNRD1 and in vitro inhibition analysis proved that chelerythrine or sanguinarine is primarily bound to the Sec498 residue of the enzyme, but the neighboring Cys497 and remaining N-terminal redox-active cysteines could also be modified after the conjugation of Sec498. With high similarity to sanguinarine, chelerythrine exhibited cytotoxic effects on multiple gastric cancer cell lines and suppressed the proliferation of tumor spheroids derived from NCI-N87 cells. Chelerythrine elevated cellular levels of reactive oxygen species (ROS) and induced endoplasmic reticulum (ER) stress. Moreover, the ROS induced by chelerythrine could be completely suppressed by the addition of N-acetyl-L-cysteine (NAC), and the same is true for sanguinarine. Notably, Nec-1, an RIPK1 inhibitor, rescued the chelerythrine-induced rapid cell death, indicating that chelerythrine triggers necroptosis in gastric cancer cells. Taken together, this study demonstrates that chelerythrine is a novel inhibitor of TXNRD1 by targeting Sec498 and possessing high anti-tumor properties on multiple gastric cancer cell lines by eliciting necroptosis.

Sanziguben polysaccharides improve diabetic nephropathy in mice by regulating gut microbiota to inhibit the TLR4/NF-κB/NLRP3 signalling pathway.

CONTEXT: Sanziguben (SZGB) is an empirical prescription used in traditional Chinese medicine to treat diabetic nephropathy (DN). As an abundant and primarily effective component of SZGB, Sanziguben polysaccharides (SZP) can be digested by flora to generate biological activity. OBJECTIVE: Our study aimed to clarify the potential mechanism of SZP in improving chronic DN. MATERIALS AND METHODS: Male db/db mice were randomized into DN, SZP (500 mg/kg) and metformin (MET, 300 mg/kg) groups. Wild-type littermates served as the normal control (NC) group. The drug was orally administered for 8 weeks. Enzyme-linked immunosorbent assay was used to detect the inflammatory factors. Proteins related to inflammation were evaluated using western blotting and immunohistochemical examination. Gut microbiota was analysed using 16S rRNA sequencing. RESULTS: SZP significantly reduced 24 h urine albumin (p < 0.05) of DN mice. Compared to DN group, SZP significantly decreased the homeostasis model assessment of insulin resistance index, serum creatinine and blood urea nitrogen levels (20.27 ± 3.50 vs. 33.64 ± 4.85, 19.22 ± 3.77 vs. 32.52 ± 3.05 µmol/L, 13.23 ± 1.42 vs. 16.27 ± 0.77 mmol/L, respectively), and mitigated renal damage. SZP also regulated gut microbiota and decreased the abundance of Gram-negative bacteria (Proteobacteria, Klebsiella and Escherichia-Shigella). Subsequently, SZP reduced lipopolysaccharides levels (1.06- to 1.93-fold) of DN mice. Furthermore, SZP inhibited the expression levels of TLR4, phospho-NF-κB p65, NLRP3 proteins and interleukin (IL)-18 and IL-1ß. CONCLUSIONS: These results demonstrated that SZP improved intestinal flora disorder and inhibited the TLR4/NF-κB/NLRP3 pathway to alleviate DN.

Tailored Zwitterionic Hemicyanine Reporters for Early Diagnosis and Prognostic Assessment of Acute Renal Failure.

Drug-induced renal failure (DIRF) poses a serious medical complication with high mortality risk. However, early diagnosis or prognosis of DIRF remain challenging, as current methods rely on detecting late-stage biomarkers. Herein we present a library of zwitterionic unimolecular hemicyanines (ZCs) available for constructing activatable reporters to detect DIRF since its initial stage. Zwitterionic properties of these probes are achieved through interspersedly integrating alkyl sulfonates and quaternary ammonium cations onto hemicyanine skeleton, which result in record low plasma protein binding (<5 %) and remarkable renal clearance efficiencies (≈96 %). An activatable reporter ZCRR is further developed by masking the optimal candidate ZC6 with a tetrapeptide specifically cleavable by caspase-8, an initiating indicator of apoptosis. In living mice with cisplatin-induced DIRF, systematically administered ZCRR efficiently accumulates in kidneys and responds to elevated caspase-8 for near-infrared fluorescence signals 'turn-on', enabling sensitive detection of intrarenal apoptosis 60 h earlier than clinical methods, and precise evaluation of apoptosis remediation effects by different medications on DIRF mice. As it's urinary excretable, ZCRR also allows for remote detection of DIRF and predicting renoprotective efficacy through in vitro optical urinalysis. This study thus presents unimolecular renal clearable scaffolds that are applicable to developing versatile activatable reporters for renal diseases management.

Size-Transformable Superoxide-Triggered Nanoreporters for Crosstalk-Free Dual Fluorescence/Chemiluminescence Imaging and Urinalysis in Living Mice.

Chemiluminescence imaging has been recognized as a valuable tool for ultrasensitive detection of physio-pathological events through elimination of background autofluorescence. However, most chemiluminescent nanoprobes suffer from shallow imaging depths and slow clearance from living bodies, which impede their use in clinical settings. We herein report size-transformable nanoreporters (ADN1 and ADN2) that could be activated at disease site by superoxide anion (O2 ⋅- ) to trigger nanostructure disassembly into renal excretable fluorescent fragments as well as chemiluminescence turn-on for crosstalk-free duplex chemo-fluorescence imaging and in vitro urinalysis. In peritonitis mouse model, we demonstrate that the representative nanoreporter ADN1 spontaneously accumulates at the disrupted peritoneum and is cleaved by upregulated O2 ⋅- to initiate depolymerization and result in red chemiluminescence at 620 nm, enabling sensitive detection of peritonitis at least 19 h earlier than gold standard histological assays. Additionally, the incorporation of a near-infrared (NIR) dye into ADN1 results in ADN2 exhibiting intense and red-shifted chemiluminescence at ≈800 nm, which permits early detection of deeply seated diseases such as drug-induced hepatotoxicity. This study thus showcases a modular design strategy that is not only applicable to developing versatile chemiluminescent nanoprobes with switchable pharmacokinetics for early disease diagnosis, but also promising for future clinical translations.

Electrophysiological characterization of photoreceptor-like cells in human inducible pluripotent stem cell-derived retinal organoids during in vitro maturation.

Retinal organoids (ROs) derived from human inducible pluripotent stem cells (hiPSCs) exhibit considerable therapeutic potential. However, current quality control of ROs during in vitro differentiation is largely limited to the detection of molecular markers, often by immunostaining, polymerase chain reaction (PCR) assays and sequencing, often without proper functional assessments. As such, in the current study, we systemically characterized the physiological maturation of photoreceptor-like cells in hiPSC-derived ROs. By performing patch-clamp recordings from photoreceptor-like cells in ROs at distinct differentiation stages (ie, Differentiation Day [D]90, D150, and D200), we determined the electrophysiological properties of the plasma membrane and several characteristic ion channels closely associated with the physiological functions of the photoreceptors. Ionic hallmarks, such as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and cyclic nucleotide-gated (CNG) channels, matured progressively during differentiation. After D200 in culture, these characteristic currents closely resembled those in macaque or human native photoreceptors. Furthermore, we demonstrated that the hyperpolarization-activated inward current/depolarization-activated outward current ratio (I-120 /I+40 ), termed as the inward-outward current (IOC) ratio hereon, accurately represented the maturity of photoreceptors and could serve as a sensitive indicator of pathological state. Thus, this study provides a comprehensive dataset describing the electrophysiological maturation of photoreceptor-like cells in hiPSC-derived ROs for precise and sensitive quality control during RO differentiation.

Mussel-inspired PDA-based MIP-SERS sensor for the detection of trace MG in environmental water.

The abuse of antibiotics such as malachite green (MG) has caused its residues in foods and environmental water, and therefore, it is important to establish a rapid and reliable method for sensitive detection of antibiotics. In this work, a novel molecularly imprinted polymer surface-enhanced Raman spectroscopy (SERS) sensor integrating high sensitivity, selectivity, and reusability is fabricated for the detection of trace MG in environmental water. SiO2@Au, by adjusting the gap between nanoparticles, provides SERS activity, and then the template MG is molecularly imprinted and wrapped by oxidative self-polymerization properties of dopamine (SA-100@MIP). The prepared SA-100@MIP achieved sensitive and selective detection of MG in pond water (0.1 nM) and presented a good linear correlation in the range of 10-6-10-10 M. Moreover, the substrate still has excellent SERS performance after 12 times of repeated use. These properties indicate that this sensor may provide broad prospects for the practical application of SERS in food and environmental monitoring.

Diagnostic challenges in primary cardiac lymphoma, the opportunity of 18F-FDG PET/CT integrated with contrast-enhanced CT.

BACKGROUND: The purpose of this study was to retrospectively evaluate the value of 18F-FDG PET/CT integrated with contrast-enhanced CT (CECT) in the differential diagnosis of primary cardiac lymphomas (PCLs) and primary cardiac angiosarcomas (PCAs). METHODS: Clinical and imaging data of patients with PCLs and PCAs were collected. All patients underwent preoperative 18F-FDG PET/CT and thoracic CECT. The enhancement pattern and tumor morphology were analyzed using CECT images. The intensity- and volume-based PET parameters of cardiac lesions were analyzed. The performance characteristics of all parameters were assessed. RESULTS: Nine patients with PCL and eight patients with PCA were analyzed. There were significant differences in SUVmax (t = 3.790, P = .002), SUVmean (t = 4.273, P = .001), metabolic tumor volume (U = 13.00, P = .027), tumor-to-liver ratio (U = 10.00, P = .011), and total lesion glycolysis (U = 4.0, P = .001) between PCLs and PC18As. There were significant differences in the enhancement pattern of tumors (P = .002) and tumor morphology (P = .015). The combination of F-FDG PET/CT and CECT improved the diagnostic accuracy, and the combination cutoff (SUVmean > 5.17) could reach 100%, but the difference was not statistically significant (P > .05). CONCLUSION: The intensity- and volume-based PET parameters of PCL were significantly higher than those of PCA. The enhancement pattern and tumor morphology were also different. According to these characteristics, the two most common types of primary cardiac malignancies can be differentiated.

Systemic pharmacological verification of Baixianfeng decoction regulating TNF-PI3K-Akt-NF-κB pathway in treating rheumatoid arthritis.

Traditional Chinese medicine has a long history of treating complex diseases, especially for the conditioning of systemic diseases. It has been reported that Baixianfeng (BXF) decoction used to treat rheumatoid arthritis (RA) may be due to its systemic regulatory effect, but the specific mechanism still remains to be elucidated. The research philosophy and methods of systemic pharmacology were used to explore the mechanism of BXF decoction in treating RA in this study. TCMSP database was used to search the ingredients of BXF decoction and screen the ADME parameters. The parameter index was set as OB ≥ 30%, DL ≥ 0.18, HL ≥ 4 h. The targets of the screened compounds were searched and predicted by TCMSP and Target-Prediction platforms. The disease targets of RA were obtained through the DisGeNET, OMIM, and PharmGkb databases. A series of network construction and analysis relied on Cytoscape 3.2.1 software, and the DAVID database was used for pathway enrichment. The adjuvant arthritis rat model was used for the verification of animal experiments to verify the predicted pathway results in terms of pathological phenotype, inflammatory factors, and pathway protein expression. The results showed that the related targets of 81 active ingredients in the drug crossed 56 targets of RA, and these common targets were enriched in 83 significant pathways, among which the TNF signaling pathway had research significance. Animal experiments have proved that BXF decoction was effective in treating adjuvant arthritis rats. The drug relieved the pathological phenotype of rats in dose-dependent. It reduced the serum content of TNF-α and IL-1ß, and reduced the gene expression of TNF-α and IL-6 in spleen tissue. In the cartilage tissue protein of rats, it inhibited the degradation of collagen Ⅱ protein. Further, BXF decoction reduced the activation of p-PI3K, p-Akt, and p-P65 protein, and decreased the overexpression of apoptotic proteins such as cleaved-caspase8 and cleaved-caspase3 in cartilage tissue. Meanwhile, it inhibited the protein expression of MMP9, TNF-α, IL-6, and IL-1ß. In conclusion, this study successfully practiced the combination of systemic pharmacology and experimental verification, and clarified that BXF decoction inhibited the progression of adjuvant arthritis rats through the TNF-PI3K-Akt-NF-κB signal axis. It provides new evidence for the study of the mechanism of BXF decoction in treating RA.

Therapeutic Efficacy of a Staged Hybrid Technique vs. Coronary Artery Bypass Surgery Grafting in The Treatment of Multi-Vessel Coronary Artery Disease.

OBJECTIVE: Hybrid coronary revascularization (HCR) integrates the advantages of coronary artery bypass surgery grafting (CABG) and percutaneous coronary intervention (PCI) and provides another effective treatment for multi-vessel coronary artery disease (CAD). This study aimed to investigate the short- and intermediate-term efficacies of a staged hybrid technique vs. CABG in treating older patients with multi-vessel CAD. METHODS: Patients, who received elective revascularization for multi-vessel CAD between May 2016 and May 2018, were recruited. They were divided into the CABG group (N = 38) and HCR group (N = 38). The major adverse cardiovascular and cerebrovascular events (MACCE), including myocardial infarction and stroke, were recorded. The results of death and second revascularization also were recorded. RESULTS: In this study, 90.1% of patients received follow up for a median time of 24 months. At 60 days after surgery, the cumulative mortality in the CABG group was significantly higher than in the HCR group, but the incidence of second revascularization in the CABG group was markedly lower than in the HCR group. The incidence of MACCE was comparable between the two groups. CONCLUSION: In older patients with multi-vessel CAD, the mortality after CABG is higher than after HCR, but the incidence of second revascularization after CABG is lower than after HCR.

C/N-Dependent Element Bioconversion Efficiency and Antimicrobial Protein Expression in Food Waste Treatment by Black Soldier Fly Larvae.

The black soldier fly (BSF), Hermetia illucens, has emerged as a promising species for waste bioconversion and source of antimicrobial proteins (AMPs). However, there is a scarcity of research on the element transformation efficiency and molecular characterization of AMPs derived from waste management. Here, food waste treatment was performed using BSF larvae (BSFL) in a C/N ratio of 21:1−10:1, with a focus on the C/N-dependent element bioconversion, AMP antimicrobial activity, and transcriptome profiling. The C-larvae transformation rates were found to be similar among C/Ns (27.0−35.5%, p = 0.109), while the N-larvae rates were different (p = 0.001), with C/N 21:1−16:1 (63.5−75.0%) being higher than C/N 14:1−10:1 (35.0−45.7%). The C/N ratio did not alter the antimicrobial spectrum of AMPs, but did affect the activities, with C/N 21:1 being significantly lower than C/N 18:1−10:1. The lysozyme genes were found to be significantly more highly expressed than the cecropin, defensin, and attacin genes in the AMP gene family. Out of 51 lysozyme genes, C/N 18:1 and C/N 16:1 up-regulated (p < 0.05) 14 and 12 genes compared with C/N 21:1, respectively, corresponding to the higher activity of AMPs. Overall, the element bioconversion efficiency and AMP expression can be enhanced through C/N ratio manipulation, and the C/N-dependent transcriptome regulation is the driving force of the AMP difference.

Carboxymethyl Chitosan and Gelatin Hydrogel Scaffolds Incorporated with Conductive PEDOT Nanoparticles for Improved Neural Stem Cell Proliferation and Neuronal Differentiation.

Tissue engineering scaffolds provide biological and physiochemical cures to guide tissue recovery, and electrical signals through the electroactive materials possess tremendous potential to modulate the cell fate. In this study, a novel electroactive hydrogel scaffold was fabricated by assembling poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles on a carboxymethyl chitosan/gelatin (CMCS/Gel) composite hydrogel surface via in situ chemical polymerization. The chemical structure, morphology, conductivity, porosity, swelling rate, in vitro biodegradation, and mechanical properties of the prepared hydrogel samples were characterized. The adhesion, proliferation, and differentiation of neural stem cells (NSCs) on conductive hydrogels were investigated. The CMCS/Gel-PEDOT hydrogels exhibited high porosity, excellent water absorption, improved thermal stability, and adequate biodegradability. Importantly, the mechanical properties of the prepared hydrogels were similar to those of brain tissue, with electrical conductivity up to (1.52 ± 0.15) × 10-3 S/cm. Compared to the CMCS/Gel hydrogel, the incorporation of PEDOT nanoparticles significantly improved the adhesion of NSCs, and supported long-term cell growth and proliferation in a three-dimensional (3D) microenvironment. In addition, under the differentiation condition, the conductive hydrogel also significantly enhanced neuronal differentiation with the up-regulation of ß-tubulin III expression. These results suggest that CMCS/Gel-PEDOT hydrogels may be an attractive conductive substrate for further studies on neural tissue repair and regeneration.

An Organic Solvent-Free Method for the Extraction of Ellagic Acid Compounds from Raspberry Wine Pomace with Assistance of Sodium Bicarbonate.

Industrial processing of raspberry juice and wine generates considerable byproducts of raspberry pomace. Ellagic acids/ellagitannins, being characterized by their antioxidant and antiproliferation properties, constitute the majority of polyphenolics in the pomace and are valuable for recovery. In the present study, we developed a novel procedure with sodium bicarbonate assisted extraction (SBAE) to recover ellagic acid from raspberry wine pomace. Key parameters in the procedure, i.e., sodium bicarbonate concentration, temperature, time and solid/liquid (S/L) ratio, were investigated by single factor analysis and optimized subsequently by Response Surface Methodology (RSM). Optimal parameters for the SBAE method here were found to be 1.2% (w/v) NaHCO3, 1:93 (w/v) S/L ratio, 22 min and 100 °C. Under these conditions, the ellagic acid yield was 6.30 ± 0.92 mg/g pomace with an antioxidant activity of 79.0 ± 0.96 µmol Trolox eq/g pomace (DPPH assay), which are 2.37 and 1.32 times the values obtained by extraction with methanol-acetone-water solvent, respectively. The considerable improvement in ellagic acid extraction efficiency could be highly attributed to the reactions of lipid saponification and ellagitannin hydrolysis resulted from sodium bicarbonates. The present study has established an organic solvent-free method for the extraction of ellagic acid from raspberry wine pomace, which is feasible and practical in nutraceutical applications.

Evaluation of the diagnostic value of joint PET myocardial perfusion and metabolic imaging for vascular stenosis in patients with obstructive coronary artery disease.

BACKGROUND: To investigate the diagnostic value of joint PET myocardial perfusion and metabolic imaging for vascular stenosis in patients with suspected obstructive coronary artery disease (CAD). METHODS: Eighty-eight patients (53 and 35 applied for training and validation, respectively) with suspected obstructive CAD were referred to 13N-NH3 PET/CT myocardial perfusion imaging (MPI) and 18F-FDG PET/CT myocardial metabolic imaging (MMI) with available coronary angiography for analysis. One semi-quantitative indicator summed rest score (SRS) and five quantitative indicators, namely, perfusion defect extent (EXT), total perfusion deficit (TPD), myocardial blood flow (MBF), scar degree (SCR), and metabolism-perfusion mismatch (MIS), were extracted from the PET rest MPI and MMI scans. Different combinations of indicators and seven machine learning methods were used to construct diagnostic models. Diagnostic performance was evaluated using the sum of four metrics (noted as sumScore), namely, area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: In univariate analysis, MIS outperformed other individual indicators in terms of sumScore (2.816-3.042 vs 2.138-2.908). In multivariate analysis, support vector machine (SVM) consisting of three indicators (MBF, SCR, and MIS) achieved the best performance (AUC 0.856, accuracy 0.810, sensitivity 0.838, specificity 0.757, and sumScore 3.261). This model consistently achieved significantly higher AUC compared with the SRS method for four specific subgroups (0.897, 0.839, 0.875, and 0.949 vs 0.775, 0.606, 0.713, and 0.744; P = 0.041, 0.005, 0.034 0.003, respectively). CONCLUSIONS: The joint evaluation of PET rest MPI and MMI could improve the diagnostic performance for obstructive CAD. The multivariate model (MBF, SCR, and MIS) combined with SVM outperformed other methods.