Healing Houses systematic review: design, sustainability, opportunities and barriers facing Soteria and peer respite development.

BACKGROUND: Soteria houses and peer respites, collectively called Healing Houses, are alternatives to psychiatric hospitalisation. AIMS: The aim of this research is to review Healing Houses in relation to design characteristics (architectural and service), sustainability and development opportunities and barriers. METHODS: This systematic review followed a PROSPERO protocol (CRD42022378089). Articles were identified from journal database searches, hand searching websites, Google Scholar searches, expert consultation and backwards and forward citation searches. RESULTS: Eight hundred and forty-nine documents were screened in three languages (English, German and Hebrew) and 45 documents were included from seven countries. The review highlights 11 architectural design characteristics (atmosphere, size, soft room, history, location, outdoor space, cleanliness, interior design, facilities, staff only areas and accessibility), six service design characteristics (guiding principles, living and working together, consensual treatment, staff, supporting personal meaning making and power), five opportunities (outcomes, human rights, economics, hospitalization and underserved) and four types of barriers (clinical, economic and regulatory, societal and ideological). The primary sustainability issue was long-term funding. CONCLUSION: Future research should focus on operationalizing a "home-like" atmosphere and the impact of design features such as green spaces on wellbeing of staff and service users. Future research could also produce design guidelines for Healing Houses.

Individualized medication of venetoclax based on therapeutic drug monitoring in Chinese acute myeloid leukemia patients using an HPLC method.

OBJECTIVE: The aim of this study was to establish a simple and sensitive high-performance liquid chromatography method for therapeutic drug monitoring of venetoclax (VEN) and optimize regimens. METHODS: The analysis required the extraction of a 50 µl plasma sample and the precipitation of proteins using acetonitrile extraction. The chromatographic method employed a mobile phase of acetonitrile: 0.5% KH2PO4 (pH 3.5) (60/40, v/v) on a Diamond C18 (4.6 mm × 250 mm, 5 µm) column at a flow rate of 1.0 ml/min. The quantitative method was validated based on standards described in 'Bioanalytical Method Validation: Guidance for Industry' published by the US Food and Drug Administration (FDA). RESULTS: The calibration curve was linear (R2 = 0.9998) over the range of 75-4800 ng/ml, with limits of quantification of 25 ng/ml. The coefficients of intraday and interday validation, specificity, recovery, and stability all met the criteria of FDA guidance. The method was successfully applied to analyze VEN concentrations in 30 cases of acute myeloid leukemia patients. The peak concentration (Cmax) was 1881.19 ±â€…756.61 ng/ml, while the trough concentration (Cmin) was 1212.69 ±â€…767.92 ng/ml in acute myeloid leukemia patients. CONCLUSION: Our study establishes a simple, precise, and sensitive high-performance liquid chromatography method for monitoring VEN and confirms its applicability for therapeutic drug monitoring of VEN in hematological cancers.

Formation of lipid-derived volatile products through lipoxygenase (LOX)- and hydroperoxide lyase (HPL)- mediated pathway in oat, barley and soy bean.

The aim of this study was to explore the formation of volatile lipid oxidation products by the lipoxygenase (LOX)-hydroperoxide lyase (HPL)-mediated pathway in oat, barley and soy bean. LOX activity was found only in barley and soy bean samples, but the lipase and HPL activity was detected in all samples. HPL showed particularly high activity with 13-hydroperoxides, while the activity was quite low when using 9-hydroperoxides, especially in the oat and barley. The optimum pH for HPL in different samples was similar, i.e., pH 6-7. In this condition, the volatile compounds formed dramatically with aldehydes and furans as the dominant products. Furthermore, a remarkable enzymatic degradation of lipids occurred during the preparation of food models with highly refined rapeseed oil (RO) and rapeseed oil fatty acid (ROFA) emulsions, where the ROFAs were more prone to oxidation than RO. This study shows the significance of lipid-degrading enzymes in plant-food flavour formation.

DNAzyme-RCA-based colorimetric and lateral flow dipstick assays for the point-of-care testing of exosomal m5C-miRNA-21.

Methylation of microRNAs (miRNAs) is a post-transcriptional modification that affects miRNA activity by altering the specificity of miRNAs to target mRNAs. Abnormal methylation of miRNAs in cancer suggests their potential as a tumor marker. However, the traditional methylated miRNA detection mainly includes mass spectrometry, sequencing and others; complex procedures and reliance on large instruments greatly limit their application in point-of-care testing (POCT). Based on this, we developed DNAzyme-RCA-based gold nanoparticle (AuNP) colorimetric and lateral flow dipstick (LFD) assays to achieve convenient detection of exosomal 5-methylcytosine miRNA-21 (m5C-miRNA-21) for the first time. The two assays achieved specific recognition and linear amplification of m5C-miRNA-21 through the DNAzyme triggered RCA reaction and color output with low background interference through AuNP aggregation induced by base complementary pairing. The lowest concentration of m5C-miRNA-21 visible to the naked eye of the two assays can reach 1 pM and 0.1 pM, respectively. Detection of exosomal m5C-miRNA-21 in clinical blood samples showed that the expression level of m5C-miRNA-21 in colorectal cancer patients was significantly higher than that in healthy individuals. This approach not only demonstrates a new strategy for the detection of colorectal cancer but also provides a reference for the development of novel diagnostic tools for other miRNA methylation-related diseases.

Converting kitchen waste into value-added fertilizer using thermophilic semi-continuous composting-biofiltration two-stage process with minimized NH3 emission.

Thermophilic semi-continuous composting (TSC) is effective for kitchen waste (KW) treatment, but large amounts of NH3-rich odorous gas are generated. This study proposes a TSC-biofiltration (BF) two-stage process. Compost from the front-end TSC was used as the packing material in the BF to remove NH3 from the exhaust gas. The BF process was effective in removing up to 83.7 % of NH3, and the NH3 content was reduced to < 8 ppm. Seven days of BF improved the quality of the product from TSC by enhancing the germination index to 134.6 %, 36.5 % higher than that in the aerated-only group. Microbial community analysis revealed rapid proliferation and eventual dominance in the BF of members related to compost maturation and the nitrogen cycle from Actinobacteria, Proteobacteria, Chloroflexi, and Bacteroidetes. The results suggest that the TSC-BF two-stage process is effective in reducing NH3 emissions from TSC and improving compost quality.

Lycorine relieves the CCl4-induced liver fibrosis mainly via the JAK2/STAT3 and PI3K/AKT signaling pathways.

Liver fibrosis, a progressive process of fibrous scarring, results from the accumulation of extracellular matrix proteins (ECM). If left untreated, it often progresses to diseases such as cirrhosis and hepatocellular carcinoma. Lycorine, a natural alkaloid derived from medicinal plants, has shown diverse bioactivities by targeting JAK2/STAT3 signaling, but its pharmacological effects and potential molecular mechanisms in liver fibrosis remains largely unexplored. The purpose of this study is to elucidate the pharmacological activity and molecular mechanism of lycorine in anti-hepatic fibrosis. Findings indicate that lycorine significantly inhibited hepatic stellate cells (HSCs) activation by reducing the expression of α-SMA and collagen-1. In vivo, lycorine treatment alleviated carbon tetrachloride (CCl4) -induced mice liver fibrosis, improving liver function, decreasing ECM deposition, and inhibiting fibrosis-related markers' expression. Mechanistically, it was found that lycorine exerts protective activity through the JAK2/STAT3 and PI3K/AKT signaling pathways, as evidenced by transcriptome sequencing technology and small molecule inhibitors. These results underscore lycorine's potential as a therapeutic drug for liver fibrosis.

Triptolide decreases podocytes permeability by regulating TET2-mediated hydroxymethylation of ZO-1.

Podocyte injury or dysfunction can lead to proteinuria and glomerulosclerosis. Zonula occludens 1 (ZO-1) is a tight junction protein which connects slit diaphragm (SD) proteins to the actin cytoskeleton. Previous studies have shown that the expression of ZO-1 is decreased in chronic kidney disease (CKD). Thus, elucidation of the regulation mechanism of ZO-1 has considerable clinical importance. Triptolide (TP) has been reported to exert a strong antiproteinuric effect by inhibiting podocyte epithelial mesenchymal transition (EMT) and inflammatory response. However, the underlying mechanisms are still unclear. We found that TP upregulates ZO-1 expression and increases the fluorescence intensity of ZO-1 in a puromycin aminonucleoside (PAN)-induced podocyte injury model. Permeablity assay showed TP decreases podocyte permeability in PAN-treated podocyte. TP also upregulates the DNA demethylase TET2. Our results showed that treatment with the DNA methyltransferase inhibitors 5-azacytidine (5-AzaC) and RG108 significantly increased ZO-1 expression in PAN-treated podocytes. Methylated DNA immunoprecipitation (MeDIP) and hydroxymethylated DNA immunoprecipitation (hMeDIP) results showed that TP regulates the methylation status of the ZO-1 promoter. Knockdown of TET2 decreased ZO-1 expression and increased methylation of its promoter, resulting in the increase of podocyte permeability. Altogether, these results indicate that TP upregulates the expression of ZO-1 and decreases podocyte permeability through TET2-mediated 5 mC demethylation. These findings suggest that TP may alleviate podocyte permeability through TET2-mediated hydroxymethylation of ZO-1.

Anaerobic digestion integrated with microbial electrolysis cell to enhance biogas production and upgrading in situ.

Anaerobic digestion (AD) is an effective and applicable technology for treating organic wastes to recover bioenergy, but it is limited by various drawbacks, such as long start-up time for establishing a stable process, the toxicity of accumulated volatile fatty acids and ammonia nitrogen to methanogens resulting in extremely low biogas productivities, and a large amount of impurities in biogas for upgrading thereafter with high cost. Microbial electrolysis cell (MEC) is a device developed for electrosynthesis from organic wastes by electroactive microorganisms, but MEC alone is not practical for production at large scales. When AD is integrated with MEC, not only can biogas production be enhanced substantially, but also upgrading of the biogas product performed in situ. In this critical review, the state-of-the-art progress in developing AD-MEC systems is commented, and fundamentals underlying methanogenesis and bioelectrochemical reactions, technological innovations with electrode materials and configurations, designs and applications of AD-MEC systems, and strategies for their enhancement, such as driving the MEC device by electricity that is generated by burning the biogas to improve their energy efficiencies, are specifically addressed. Moreover, perspectives and challenges for the scale up of AD-MEC systems are highlighted for in-depth studies in the future to further improve their performance.

Response mechanisms of different Saccharomyces cerevisiae strains to succinic acid.

BACKGROUND: The production of succinic acid (SA) from biomass has attracted worldwide interest. Saccharomyces cerevisiae is preferred for SA production due to its strong tolerance to low pH conditions, ease of genetic manipulation, and extensive application in industrial processes. However, when compared with bacterial producers, the SA titers and productivities achieved by engineered S. cerevisiae strains were relatively low. To develop efficient SA-producing strains, it's necessary to clearly understand how S. cerevisiae cells respond to SA. RESULTS: In this study, we cultivated five S. cerevisiae strains with different genetic backgrounds under different concentrations of SA. Among them, KF7 and NBRC1958 demonstrated high tolerance to SA, whereas NBRC2018 displayed the least tolerance. Therefore, these three strains were chosen to study how S. cerevisiae responds to SA. Under a concentration of 20 g/L SA, only a few differentially expressed genes were observed in three strains. At the higher concentration of 60 g/L SA, the response mechanisms of the three strains diverged notably. For KF7, genes involved in the glyoxylate cycle were significantly downregulated, whereas genes involved in gluconeogenesis, the pentose phosphate pathway, protein folding, and meiosis were significantly upregulated. For NBRC1958, genes related to the biosynthesis of vitamin B6, thiamin, and purine were significantly downregulated, whereas genes related to protein folding, toxin efflux, and cell wall remodeling were significantly upregulated. For NBRC2018, there was a significant upregulation of genes connected to the pentose phosphate pathway, gluconeogenesis, fatty acid utilization, and protein folding, except for the small heat shock protein gene HSP26. Overexpression of HSP26 and HSP42 notably enhanced the cell growth of NBRC1958 both in the presence and absence of SA. CONCLUSIONS: The inherent activities of small heat shock proteins, the levels of acetyl-CoA and the strains' potential capacity to consume SA all seem to affect the responses and tolerances of S. cerevisiae strains to SA. These factors should be taken into consideration when choosing host strains for SA production. This study provides a theoretical basis and identifies potential host strains for the development of robust and efficient SA-producing strains.

Strain and Electric Field Engineering of G-ZnO/SnXY (X, Y = S, Se) S-Scheme Heterostructures for Photocatalyst and Electronic Device Applications: A Hybrid DFT Calculation.

Using hybrid density functional theory calculations, we systematically study the biaxial strain and electric field modulated electronic properties of g-ZnO/SnS2, g-ZnO/SnSe2, and g-ZnO/SnSSe S-scheme van der Waals heterostructures (vdWHs). g-ZnO/SnS2 and g-ZnO/SnSSe are found to be promising photocatalysts for water splitting with high solar-to-hydrogen efficiencies, even under acidic, alkaline, and high-stress conditions. The strain effect on the bandgaps of g-ZnO/SnXY is explained in detail according to the correlation between geometry structure and orbital hybridization of SnXY, which could help understand the strain-induced band structure evolutions in other SnXY (X, Y = S, Se)-based vdWHs. It is surprising that under an external electric field, g-ZnO/SnS2, g-ZnO/SnSe2, and g-ZnO/SnSSe can offer the occupied nearly free-electron (NFE) states. In many materials, NFE states are usually unoccupied and is not conducive to the charge transport. The NFE state in g-ZnO/SnSe2 is the most sensitive to the electric field and might be promising electron transport channel in nanoelectronic devices. g-ZnO/SnSe2 might also have application potential in gas sensors and high-temperature superconductors.

Ldl-stimulated microglial activation exacerbates ischemic white matter damage.

The role of microglia in triggering the blood-brain barrier (BBB) impairment and white matter damage after chronic cerebral hypoperfusion is unclear. Here we demonstrated that the vessel-adjacent microglia were specifically activated by the leakage of plasma low-density lipoprotein (LDL), which led to BBB breakdown and ischemic demyelination. Interestingly, we found that LDL stimulation enhanced microglial phagocytosis, causing excessive engulfment of myelin debris and resulting in an overwhelming lipid burden in microglia. Surprisingly, these lipid-laden microglia exhibited a suppressed profile of inflammatory response and compromised pro-regenerative properties. Microglia-specific knockdown of LDLR or systematic medication lowering circulating LDL-C showed protective effects against ischemic demyelination. Overall, our findings demonstrated that LDL-stimulated vessel-adjacent microglia possess a disease-specific molecular signature, characterized by suppressed regenerative properties, which is associated with the propagation of demyelination during ischemic white matter damage.

High synthetic cost-amino acids reduce member interactions of acetate-degrading methanogenic microbial community.

Introduction: The cooperation among members of microbial communities based on the exchange of public goods such as 20 protein amino acids (AAs) has attracted widespread attention. However, little is known about how AAs availability affects interactions among members of complex microbial communities and the structure and function of a community. Methods: To investigate this question, trace amounts of AAs combinations with different synthetic costs (low-cost, medium-cost, high-cost, and all 20 AAs) were supplemented separately to acetate-degrading thermophilic methanogenic reactors, and the differences in microbial community structure and co-occurring networks of main members were compared to a control reactor without AA supplementation. Results: The structure of the microbial community and the interaction of community members were influenced by AAs supplementation and the AAs with different synthetic costs had different impacts. The number of nodes, links, positive links, and the average degree of nodes in the co-occurrence network of the microbial communities with AAs supplementation was significantly lower than that of the control without AAs supplementation, especially for all 20 AAs supplementation followed by the medium- and high-cost AAs supplementation. The average proportion of positive interactions of microbial members in the systems supplemented with low-cost, medium-cost, high-cost, all AAs, and the control group were 0.42, 0.38, 0.15, 0.4, and 0.45, respectively. In addition, the ecological functions of community members possibly changed with the supplementation of different cost AAs. Discussion: These findings highlight the effects of AAs availability on the interactions among members of complex microbial communities, as well as on community function.

Rare-Earth Metal Complexes Supported by A Tridentate Amidinate Ligand: Synthesis, Characterization, and Catalytic Comparison in Isoprene Polymerization.

To systematically investigate the dependence of the initiating group and metal size on polymerization performance, a family of rare-earth metal bis(alkyl)/bis(benzyl)/bis(amide) complexes supported by a monoanionic tridentate amidinate ligand [(2,6-iPr2C6H3)NC(Ph)N(C6H4-2-OMe]- (HL) were synthesized and well-characterized. Treatment of rare-earth metal tris(alkyl)/tris(benzyl)/tris(amide) complexes Y(CH2C6H4NMe2-o)3 or Y(CH2SiMe3)3(THF)2 or Ln[N(SiHMe2)2]3(THF)x (Ln = Sc, x = 1; Ln = Y, La, Sm, Lu, x = 2) with 1 equiv of HL gave the corresponding mono(amidinate) rare-earth metal bis(alkyl)/bis(benzyl)/bis(amide) complexes [(2,6-iPr2C6H4)NC(Ph)N(C6H4-2-OMe)]Y(CH2C6H4NMe2-o)2 (1), [(2,6-iPr2C6H4)NC(Ph)N(C6H4-2-OMe)]Y(CH2SiMe3)2(THF) (2), and [(2,6-iPr2C6H4)NC(Ph)N(C6H4-2-OMe)]Ln[N(SiHMe2)2]2(THF)n (Ln = Y, n = 1 (3); Ln = La, n = 1 (4); Ln = Sc, n = 0 (5); Ln = Lu, n = 0 (6); Ln = Sm, n = 0 (7)) in good isolated yields. These complexes were characterized by elemental analysis, NMR spectroscopy, and single-crystal X-ray diffraction. In the presence of excess AlMe3 and on treatment with 1 equiv of [Ph3C][B(C6F5)4], these complexes could serve as precatalysts for cationic polymerization of isoprene, in which the dependence of the polymerization activity and regioselectivity on the initiating group and metal size was observed.

A microfluidic-based gut-on-a-chip model containing the gut microbiota of patients with depression reveals physiological characteristics similar to depression.

The diverse commensal microbiome of the human intestine has been considered to play a central role in depression. However, no host-microbiota co-culture system has been developed for depression, which hinders the controlled study of the interaction between depression and gut microbiota. We designed and manufactured a microfluidic-based gut-on-a-chip model containing the gut microbiota of patients with depression (depression-on-gut-chip, DoGC), which enables the extended co-culture of viable aerobic human intestinal epithelial cells and anaerobic gut microbiota, and allows the direct study of interactions between human gut microbiota and depression. We introduced representative gut microbiota from individuals with depression into our constructed DoGC model, successfully recapitulating the gut microbiota structure of depressed patients. This further led to the manifestation of physiological characteristics resembling depression, such as reduced gut barrier function, chronic low-grade inflammatory responses and decreased neurotransmitter 5-HT levels. Metabolome analysis of substances in the DoGC revealed a significant increase in lipopolysaccharides and tyrosine, while hyodeoxycholic acid, L-proline and L-threonine were significantly reduced, indicating the occurrence of depression. The proposed DoGC can serve as an effective platform for studying the gut microbiota of patients with depression, providing important cues for their roles in the pathology of this condition and acting as a powerful tool for personalized medicine.

A stable colorimetric biosensor for highly selective detection of malathion residue in food based on aptamer-regulated laccase-mimic activity.

Malathion causes a serious threat to human health due to its widespread use in the environment. Herein, a novel and stable smartphone-integrated colorimetric biosensor for malathion detection is firstly established based on aptamer-enhanced laccase-mimicking activity. The results indicate that the M17-F aptamer can increase the affinity of Ag2O nanoparticles to the substrate 2,4-dichlorophenol and enhance their laccase-mimicking activity. Thus, abundant semiquinone radicals are produced in the catalytic system, which are combined with chromogenic agent to generate dark red products. The corresponding RGB values for the colour change of the solution can be easily obtained using smartphones, which is used for the rapid detection of malathion. The established biosensor for malathion has a limit of detection as low as 5.85 nmol·L-1, and displays good selectivity for other competitive pesticides. Moreover, further studies have verified the applicability of the biosensor in actual samples, indicating that it may have the potential for application in malathion detection in food.

Characterization of the ADP-ß-D-manno-heptose biosynthetic enzymes from two pathogenic Vibrio strains.

ADP-activated ß-D-manno-heptoses (ADP-ß-D-manno-heptoses) are precursors for the biosynthesis of the inner core of lipopolysaccharide in Gram-negative bacteria. Recently, ADP-D-glycero-ß-D-manno-heptose (ADP-D,D-manno-heptose) and its C-6'' epimer, ADP-L-glycero-ß-D-manno-heptose (ADP-L,D-manno-heptose), were identified as potent pathogen-associated molecular patterns (PAMPs) that can trigger robust innate immune responses. Although the production of ADP-D,D-manno-heptose has been studied in several different pathogenic Gram-negative bacteria, current knowledge of ADP-ß-D-manno-heptose biosynthesis in Vibrio strains remains limited. Here, we characterized the biosynthetic enzymes of ADP-D,D-manno-heptose and the epimerase that converts it to ADP-L,D-manno-heptose from Vibrio cholerae (the causative agent of pandemic cholera) and Vibrio parahaemolyticus (non-cholera pathogen causing vibriosis with clinical manifestations of gastroenteritis and wound infections) in comparison with their isozymes from Escherichia coli. Moreover, we discovered that ß-D-mannose 1-phosphate, but not α-D-mannose 1-phosphate, could be activated to its ADP form by the nucleotidyltransferase domains of bifunctional kinase/nucleotidyltransferases HldEVC (from V. cholerae) and HldEVP (from V. parahaemolyticus). Kinetic analyses of the nucleotidyltransferase domains of HldEVC and HldEVP together with the E. coli-derived HldEEC were thus carried out using ß-D-mannose 1-phosphate as a mimic sugar substrate. Overall, our works suggest that V. cholerae and V. parahaemolyticus are capable of synthesizing ADP-ß-D-manno-heptoses and lay a foundation for further physiological function explorations on manno-heptose metabolism in Vibrio strains. KEY POINTS: • Vibrio strains adopt the same biosynthetic pathway as E. coli in synthesizing ADP-ß-D-manno-heptoses. • HldEs from two Vibrio strains and E. coli could activate ß-D-mannose 1-phosphate to ADP-ß-D-mannose. • Comparable nucleotidyltransfer efficiencies were observed in the kinetic studies of HldEs.

In Situ Imaging of GGT and HOBr-Triggered Atherosclerotic Plaque Rupture via Activating the RunX2/Col IV Signaling Pathway.

Calcification and abnormal collagen deposition within blood vessels constitute causative factors for atherosclerotic plaque rupture, and their occurrence is intimately linked with γ-glutamyltranspeptidase (GGT) and hypobromous acid (HOBr). However, the underlying regulatory mechanisms of GGT and HOBr in plaque rupture remain unclear. Hence, we developed a dual-responsive near-infrared (NIR) fluorescent probe (BOC-H) that effectively avoids spectral crosstalk for the in situ visualization of the fluctuations in GGT and HOBr levels during atherosclerotic plaque rupture. We found that both GGT and HOBr contents increase significantly in the calcification models of cells and animals. The overexpressed GGT participated in intracellular oxygen-promoting behavior, which obviously upregulated the expression of RunX2 and Col IV by facilitating H2O2 and HOBr secretion. This process triggered calcification and abnormal collagen deposition within the plaque, which raised the risk of plaque rupture. PM2.5-induced arteriosclerotic calcification models further verified the results that GGT and HOBr accelerate plaque rupture via activation of the RunX2/Col IV signaling pathway. Moreover, the assessment of GGT and HOBr in serum samples from patients with acute myocardial infarction further confirmed the co-regulation of GGT and HOBr in the plaque rupture. Together, our studies highlight the involvement of GGT and HOBr in driving plaque rupture and offer new targets for the prevention and treatment of acute cardiovascular disease.

Impact of Corn Starch Molecular Structures on Texture, Water Dynamics, Microstructure, and Protein Structure in Silver Carp (Hypophthalmichthys molitrix) Surimi Gel.

This study systematically investigates the impact of corn starch molecular structures on the quality attributes of surimi gel products. Employing molecular analyses to characterize corn starch, three amylopectin fractions (A, B1, and B2), categorized by the degree of polymerization ranges (6 < X ≤ 12, 12 < X ≤ 24, and 24 < X ≤ 36, respectively) were specifically focused on. The surimi gel quality was comprehensively assessed through texture profile analysis, nuclear magnetic resonance, scanning electron microscopy, stained section analysis, and Fourier transform infrared spectroscopy. Results indicated the substantial volume expansion of corn amylopectin upon water absorption, effectively occupying the surimi gel matrix and fostering the development of a more densely packed protein network. Starch gels with higher proportions of A, B1, and B2 exhibited improved hardness, chewiness, and bound water content in the resultant surimi gels. The weight-average molecular weight and peak molecular weight of corn starch showed a strong positive correlation with surimi gel hardness and chewiness. Notably, the secondary structure of proteins within the surimi gel was found to be independent of corn starch's molecular structure. This study provides valuable insights for optimizing formulations in surimi gel products, emphasizing the significance of elevated A, B1, and B2 content in corn starch as an optimal choice for crafting dense, chewy, water-retaining surimi gels.

Chemically Conjugated Branched Staples for Super-DNA Origami.

DNA origami, comprising a long folded DNA scaffold and hundreds of linear DNA staple strands, has been developed to construct various sophisticated structures, smart devices, and drug delivery systems. However, the size and diversity of DNA origami are usually constrained by the length of DNA scaffolds themselves. Herein, we report a new paradigm of scaling up DNA origami assembly by introducing a novel branched staple concept. Owing to their covalent characteristics, the chemically conjugated branched DNA staples we describe here can be directly added to a typical DNA origami assembly system to obtain super-DNA origami with a predefined number of origami tiles in one pot. Compared with the traditional two-step coassembly system (yields <10%), a much greater yield (>80%) was achieved using this one-pot strategy. The diverse superhybrid DNA origami with the combination of different origami tiles can be also efficiently obtained by the hybrid branched staples. Furthermore, the branched staples can be successfully employed as the effective molecular glues to stabilize micrometer-scale, super-DNA origami arrays (e.g., 10 × 10 array of square origami) in high yields, paving the way to bridge the nanoscale precision of DNA origami with the micrometer-scale device engineering. This rationally developed assembly strategy for super-DNA origami based on chemically conjugated branched staples presents a new avenue for the development of multifunctional DNA origami-based materials.

Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections.

Introduction: Elderly patients are more prone to develop acute kidney injury during infections and polymyxin B (PMB)-associated nephrotoxicity than young patients. The differential response to PMB between the elderly and young critically ill patients is unknown. We aimed to assess PMB exposure in elderly patients compared with young critically ill patients, and to determine the covariates of PMB pharmacokinetics in critically ill patients. Methods: Seventeen elderly patients (age ≥ 65 years) and six young critically ill patients (age < 65 years) were enrolled. Six to eight blood samples were collected during the 12 h intervals after at least six doses of intravenous PMB in each patient. PMB plasma concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was PMB exposure as assessed by the area under the concentration-time curve over 24 h at steady state (AUCss, 0-24 h). Results and Discussion: The elderly group had lower total body weight (TBW) and higher Charlson comorbidity scores than young group. Neither AUCss, 0-24 h nor normalized AUCss, 0-24 h (adjusting AUC for the daily dose in mg/kg of TBW) was significantly different between the elderly group and young group. The half-life time was longer in the elderly patients than in young patients (11.21 vs 6.56 h respectively, p = 0.003). Age and TBW were the covariates of half-life time (r = 0.415, p = 0.049 and r = -0.489, p = 0.018, respectively). TBW was the covariate of clearance (r = 0.527, p = 0.010) and AUCss, 0-24 h (r = -0.414, p = 0.049). Patients with AUCss, 0-24 h ≥ 100 mg·h/L had higher baseline serum creatinine levels and lower TBW than patients with AUCss, 0-24 h < 50 mg·h/L or patients with AUCss, 0-24 h 50-100 mg·h/L. The PMB exposures were comparable in elderly and young critically ill patients. High baseline serum creatinine levels and low TBW was associated with PMB overdose. Trial registration: ChiCTR2300073896 retrospectively registered on 25 July 2023.