Post-collection purity correction for internal standard correction-high performance liquid chromatography-quantitative nuclear magnetic resonance.

Quantitative nuclear magnetic resonance (qNMR) has a potential risk of inaccurate quantification of complex organic compounds with low purity due to incomplete separation of the impurity signals and the target component signals. The high performance liquid chromatography-qNMR (HPLC-qNMR) method removes impurities from the sample by HPLC and accurately determines the purity of the sample by qNMR, avoiding the laborious, time-consuming, and costly step of qualitative and quantitative determination of impurities in conventional mass balance methods. An improved method, named post-collection purity correction for internal standard correction-HPLC-qNMR (ISC-HPLC-qNMR), was developed and demonstrated on a complex compound oxytetracycline with low purity. In this method, a correction factor was introduced to compensate for the inability to achieve 100% purity through the HPLC purification procedure. The purity value with standard deviation of the oxytetracycline study material using this method was 82.00% ± 0.82%, while that obtained from the conventional qNMR with deconvolution was 81.70% ± 0.35%. The consistency of these results demonstrated that the improved method extends the applicability to the samples where HPLC is not capable of purifying complex compounds with low purity to near 100%, especially containing highly similar structural-related impurities. Furthermore, this method allows purification and quantification without the need to identify impurities in the sample, resulting in significant savings of time and cost. Additionally, it effectively compensates for the limitations of qNMR deconvolution in handling peak overlap in the sample.

Integrating UHPLC-Q-TOF-MS/MS, Network Pharmacology, Bioinformatics and Experimental Validation to Uncover the Anti-cancer Mechanisms of TiaoPi AnChang Decoction in Colorectal Cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The TiaoPi AnChang Decoction (TPACD), a Traditional Chinese Medicine (TCM) prescription based on Xiangsha Liujunzi Decoction, has demonstrated clinical efficacy as an adjuvant therapy for colorectal cancer (CRC) patients. However, its specific ingredients and potential mechanisms of action remain unclear. AIM OF THE STUDY: To identify the primary active ingredients of TPACD, their molecular targets, and potential mechanisms underlying the efficacy of TPACD in CRC treatment. MATERIALS AND METHODS: This study investigated the clinically validated TCM formula TPACD. In vitro and in vivo experiments were used to demonstrate TPACD's regulatory effects on various malignant phenotypes of tumors, providing basic research support for its anti-cancer activity. To understand its pharmacodynamic basis, we utilized ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry (UHPLC-Q-TOF-MS/MS) to analyze TPACD constituents present in the bloodstream. Network pharmacology and bioinformatics analyses were used to identify potential active components and their molecular targets for TPACD's therapeutic effects in CRC. Subsequent experiments further elucidated its pharmacological mechanism. RESULTS: TPACD inhibits various malignant cellular processes, such as cell proliferation, apoptosis, migration, and invasion, and has shown potential anti-CRC activities both in vitro and in vivo. Following the identification of 109 constituents absorbed into the blood from TPACD, network pharmacology analysis predicted 42 potential anti-CRC targets. Clinical analyses highlighted three genes as prognostic key genes of TPACD's therapeutic action: C-X-C motif chemokine ligand 8 (CXCL8), fatty acid binding protein 4 (FABP4), and matrix metallopeptidase 3 (MMP3). Drug sensitivity analyses, molecular docking simulations and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) identified MMP3 as the most promising target for TPACD's anti-CRC action. Enzyme activity assays confirmed that TPACD inhibits MMP3 enzyme activity. Surface plasmon resonance (SPR) characterized the binding affinity between MMP3 and effective active components of TPACD, including luteolin, quercetin, kaempferol, and liensinine. CONCLUSIONS: TPACD exhibits anti-CRC activity in vitro and in vivo, with MMP3 identified as a critical target. The active compounds, including luteolin, quercetin, kaempferol, and liensinine, absorbed into the bloodstream, contribute to TPACD's efficacy by targeting MMP3.

Triclosan impairs spermatocyte cell proliferation and induces autophagy by regulating MicroRNA-20a-5P by pargeting PTEN.

BACKGROUND: Triclosan (TCS), as an endocrine disrupter, has been found to affect male fertility. However, the potential molecular mechanism is still unknown. We aimed to investigate whether the toxic effects of TCS on spermatocyte cells was mediated by the regulation of microRNA-20a-5P on PTEN. METHODS: GC-2 and TM4 cells were treated with TCS (0.5-80µM) for 24 or 48hours. Effect of TCS on proliferation of GC-2 and TM4 cells was detected using a cell counting kit-8 (CCK8) assay. Expression of miR-17 family and autophagy genes were detected. The interaction between miR-20a-5P and PTEN was determined by a dual-luciferase reporter assay. RESULTS: TCS decreased cell proliferation of GC-2 and TM4 cells. Expression of autophagy-related genes and miR-17 family was altered by TCS. PTEN expression was significantly increased, whereas the expression of miR-20a-5P was significantly decreased in GC-2 and TM4 cells. As predicted in relevant databases, there is a binding site of miR-20a-5P in PTEN. The expression of PTEN was significantly down-regulated by the miR-20a-5P mimic. CONCLUSION: As a downstream target of miR-20a-5P, PTEN functioned in the autophagy process of which TCS inhibited the proliferation of spermatocyte cells. Our results provided new ideas for revealing the molecular mechanism and protective strategy on male infertility.

Fasting alleviates bleomycin-induced lung inflammation and fibrosis via decreased Tregs and monocytes.

PURPOSE: Idiopathic pulmonary fibrosis (IPF), a chronic and progressively worsening condition characterized by interstitial lung inflammation and fibrosis of unknown etiology, has a grim prognosis. The treatment options for IPF are limited and new therapeutic strategies are urgently needed. Dietary restriction can improve various inflammatory diseases, but its therapeutic effect on bleomycin (BLM)-induced pulmonary fibrosis mouse model remains unclear. This study aims to investigate whether intermittent fasting (IF) can alleviate BLM-induced pulmonary inflammation and fibrosis. METHODS: Pulmonary fibrosis mouse models were induced by BLM. The IF group underwent 24-h fasting cycles for one week prior and three weeks following BLM administration. Meanwhile, the ad libitum feeding group had unrestricted access to food throughout the experiment. The evaluation focused on lung pathology via histological staining, qPCR analysis of collagen markers, and immune cell profiling through flow cytometry. RESULTS: IF group significantly reduced inflammation and fibrosis in lung tissues of BLM-induced mice compared to ad libitum feeding group. qPCR results showed IF remarkably decreased the mRNA expression of Col 1a and Col 3a in the lungs of BLM-induced mouse models. IF also reduced the numbers of regulatory T cells (Tregs), T helper 17 (Th17) cells, monocytes, and monocyte-derived alveolar macrophages (MoAMs) in the lung tissues. CONCLUSIONS: IF may improve BLM-induced pulmonary fibrosis by decreasing numbers of immune cells including Treg cells, Th17 â€‹cells, monocytes, and MoAMs in the lungs. This study offers experimental validation for dietary intervention as a viable treatment modality in IPF management.

Structural characterization of extracellular polysaccharides from Phellinus igniarius SH-1 and their therapeutic effects on DSS induced colitis in mice.

Phellinus igniarius is a valuable medicinal and edible mushroom, and its polysaccharides exhibit excellent anti-inflammatory activity. During liquid fermentation to produce P. igniarius mycelia, the fermentation liquid is often discarded, but it contains extracellular polysaccharides. To better utilize these resources, P. igniarius SH-1 was fermented in a 100 L fermenter, and PIPS-2 was isolated and purified from the fermentation broth. The structural characteristics and anti-inflammatory activity of PIPS-2 were determined. PIPS-2 had a molecular weight of 22.855 kDa and was composed of galactose and mannose in a molar ratio of 0.38:0.62. Structural analysis revealed that the main chain of PIPS-2 involved →2)-α-D-Manp-(1 â†’ 3)-ß-D-Galf-(1→, and the side chains involved α-D-Manp-(1 â†’ 6)-α-D-Manp-(1→, α-D-Manp-(1 â†’ 3)-α-D-Manp-(1→, and α-D-Manp-(1. PIPS-2 alleviated the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice, improved the imbalance of inflammatory factors and antioxidant enzymes, and increased short-chain fatty acid contents. Combining the intestinal flora and metabolite results, PIPS-2 was found to regulate the abundance of Firmicutes, Lachnospiraceae_NK4A136_group, Proteobacteria, Bacteroides, and many serum metabolites including hexadecenal, copalic acid, 8-hydroxyeicosatetraenoic acid, artepillin C, and uric acid, thereby ameliorating metabolite related disorders in mice with colitis. In summary, PIPS-2 may improve colitis in mice by regulating the gut microbiota and metabolites.

Screening primary carnitine deficiency in 10 million Chinese newborns: a systematic review and meta-analysis.

BACKGROUND: Primary carnitine deficiency (PCD) is a rare autosomal recessive fatty acid oxidation disorder caused by variants in SLC22A5, with its prevalence and SLC22A5 gene mutation spectrum varying across races and regions. This study aimed to systematically analyze the incidence of PCD in China and delineate regional differences in the prevalence of PCD and SLC22A5 gene variants. METHODS: PubMed, Embase, Web of Science, and Chinese databases were searched up to November 2023. Following quality assessment and data extraction, a meta-analysis was performed on screening results for PCD among Chinese newborns. RESULTS: After reviewing 1,889 articles, 22 studies involving 9,958,380 newborns and 476 PCD cases were included. Of the 476 patients with PCD, 469 underwent genetic diagnosis, revealing 890 variants of 934 alleles of SLC22A5, among which 107 different variants were detected. The meta-analysis showed that the prevalence of PCD in China was 0.05‰ [95%CI, (0.04‰, 0.06‰)] or 1/20 000 [95%CI, (1/16 667, 1/25 000)]. Subgroup analyses revealed a higher incidence in southern China [0.07‰, 95%CI, (0.05‰, 0.08‰)] than in northern China [0.02‰, 95%CI, (0.02‰, 0.03‰)] (P < 0.001). Furthermore, the result of the meta-analysis showed that the frequency of the variant with c.1400C > G, c.51C > G, c.760C > T, c.338G > A, and c.428C > T were 45% [95%CI, (34%, 59%)], 26% [95%CI, (22%, 31%)], 14% [95%CI, (10%, 20%)], 6% [95%CI, (4%, 8%)], and 5% [95%CI, (4%, 8%)], respectively. Among the subgroup analyses, the variant frequency of c.1400C > G in southern China [39%, 95%CI, (29%, 53%)] was significantly lower than that in northern China [79‰, 95%CI, (47‰, 135‰)] (P < 0.05). CONCLUSIONS: This study systematically analyzed PCD prevalence and identified common SLC22A5 gene variants in the Chinese population. The findings provide valuable epidemiological insights and guidance for future PCD screening effects in newborns.

A novel LGALS1-depended and immune-associated fatty acid metabolism risk model in acute myeloid leukemia stem cells.

Leukemia stem cells (LSCs) are recognized as the root cause of leukemia initiation, relapse, and drug resistance. Lipid species are highly abundant and essential component of human cells, which often changed in tumor microenvironment. LSCs remodel lipid metabolism to sustain the stemness. However, there is no useful lipid related biomarker has been approved for clinical practice in AML prediction and treatment. Here, we constructed and verified fatty acid metabolism-related risk score (LFMRS) model based on TCGA database via a series of bioinformatics analysis, univariate COX regression analysis, and multivariate COX regression analysis, and found that the LFMRS model could be an independent risk factor and predict the survival time of AML patients combined with age. Moreover, we revealed that Galectin-1 (LGALS1, the key gene of LFMRS) was highly expressed in LSCs and associated with poor prognosis of AML patients, and LGALS1 repression inhibited AML cell and LSC proliferation, enhanced cell apoptosis, and decreased lipid accumulation in vitro. LGALS1 repression curbed AML progression, lipid accumulation, and CD8+ T and NK cell counts in vivo. Our study sheds light on the roles of LFMRS (especially LGALS1) model in AML, and provides information that may help clinicians improve patient prognosis and develop personalized treatment regimens for AML.

Improving bee feed recipes to safeguard honeybee colonies during times of food scarcity.

In beekeeping, when natural nectar or pollen sources become limited, it is crucial to provide supplemental bee feed to maintain the viability of the bee colony. This study was conducted during the autumn food shortage season, during which bees were fed with different proportions of modified bee feed. We identified an optimal bee diet by evaluating honeybee longevity, food consumption, body weight, and gut microbe distribution, with natural pollen serving as a control diet. The results indicated that bees preferred a mixture of 65% defatted soy flour, 20% corn protein powder, 13% wheat germ flour, 2% yeast powder, and a 50% sucrose solution. This bee food recipe significantly increased the longevity, feed consumption, and body weight of bees. The group fed the natural pollen diet exhibited a greater abundance of essential intestinal bacteria. The bee diets used in this study contained higher protein levels and lower concentrations of unsaturated fatty acids and vitamins than did the diets stored within the colonies. Therefore, we propose that incorporating both bee feed and natural pollen in beekeeping practices will achieve more balanced nutritional intake.

Interaction between the Neuroprotective and Hyperglycemia Mitigation Effects of Walnut-Derived Peptide LVRL via the Wnt3a/ß-Catenin/GSK-3ß Pathway in a Type 2 Diabetes Mellitus Model.

The term type 3 diabetes mellitus (T3DM) has been considered for Alzheimer's disease (AD) due to the common molecular and cellular characteristics found between type 2 diabetes mellitus (T2DM) and cognitive deficits. However, the specific mechanism of T3DM remains elusive, especially the neuroprotective effects of dietary components in hyperglycemic individuals. In this study, a peptide, Leu-Val-Arg-Leu (LVRL), found in walnuts significantly improved memory decline in streptozotocin (STZ)- and high-fat-diet (HFD)-stimulated T2DM mouse models (p < 0.05). The LVRL peptide also mitigated hyperglycemia, enhanced synaptic plasticity, and ameliorated mitochondrial dysfunction, as demonstrated by Morris water maze tests, immunoblotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, and cellular staining. A Wnt3a inhibitor, DKK1, was subsequently used to verify the possible role of the Wnt3a/ß-Catenin/GSK-3ß pathway in glucose-induced insulin resistance in PC12 cells. In vitro LVRL treatment dramatically modulated the protein expression of p-Tau (Ser404), Synapsin-1, and PSD95, elevated the insulin level, increased glucose consumption, and relieved the mitochondrial membrane potential, and MitoSOX (p < 0.05). These data suggested that peptides like LVRL could modulate the relationship between brain insulin and altered cognition status via the Wnt3a/ß-Catenin/GSK-3ß pathway.

Integrative analysis of bulk and single-cell RNA sequencing reveals the gene expression profile and the critical signaling pathways of type II CPAM.

BACKGROUD: Type II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets. METHODS: RNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations. RESULTS: A total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition. CONCLUSIONS: In summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.

A DNA walker based on hairpin-shaped DNA aligner and fueled by nicking endonuclease for sensitive and rapid miRNA analysis.

BACKGROUND: DNA walker-based strategies have gained significant attention in nucleic acid analysis. However, they face challenges related to balancing design complexity, sequence dependence, and amplification efficiency. Furthermore, most existing DNA walkers rely on walking and lock probes, requiring optimization of various parameters like DNA probe sequence, walking-to-lock probe ratio, lock probe length, etc. to achieve optimal performance. This optimization process is time-consuming and adds complexity to experiments. To enhance the performance and reliability of DNA walker nanomachines, there is a need for a simpler, highly sensitive, and selective alternative strategy. RESULTS: A sensitive and rapid miRNA analysis strategy named hairpin-shaped DNA aligner and nicking endonuclease-fueled DNA walker (HDA-NE DNA walker) was developed. The HDA-NE DNA walker was constructed by modifying hairpin-shaped DNA aligner (HDA) probe and substrate report (SR) probe on the surface of AuNPs. Under normal conditions, HDA and SR remained stable. However, in the presence of miR-373, HDA underwent a conformational transition to an activated structure to continuously cleave the SR probe on the AuNPs with the assistance of Nt.AlwI nicking endonuclease, resulting in sensitive miRNA detection with a detection limit as low as 0.23 pM. Additionally, the proposed HDA-NE DNA walker exhibited high selectivity in distinguishing miRNAs with single base differences and can effectively analyze miR-373 levels in both normal and breast cancer patient serums. SIGNIFICANCE: The proposed HDA-NE DNA walker system was activated by a conformational change of HDA probe only in the presence of the target miRNA, eliminating the need for a lock probe and without sequence dependence for SR probe. This strategy demonstrated a rapid reaction rate of only 30 min, minimal background noise, and a high signal-to-noise ratio (S/B) compared to capture/lock-based DNA walker. The method is expected to become a powerful tool and play an important role in disease diagnosis and precision therapy.

Protective effect of zinc gluconate on intestinal mucosal barrier injury in antibiotics and LPS-induced mice.

Objective: The aim of the study is to investigate the function and mechanism of Zinc Gluconate (ZG) on intestinal mucosal barrier damage in antibiotics and Lipopolysaccharide (LPS)-induced mice. Methods: We established a composite mouse model by inducing intestinal mucosal barrier damage using antibiotics and LPS. The animals were divided into five groups: Control (normal and model) and experimental (low, medium, and high-dose ZG treatments). We evaluated the intestinal mucosal barrier using various methods, including monitoring body weight and fecal changes, assessing pathological damage and ultrastructure of the mouse ileum, analyzing expression levels of tight junction (TJ)-related proteins and genes, confirming the TLR4/NF-κB signaling pathway, and examining the structure of the intestinal flora. Results: In mice, the dual induction of antibiotics and LPS led to weight loss, fecal abnormalities, disruption of ileocecal mucosal structure, increased intestinal barrier permeability, and disorganization of the microbiota structure. ZG restored body weight, alleviated diarrheal symptoms and pathological damage, and maintained the structural integrity of intestinal epithelial cells (IECs). Additionally, ZG reduced intestinal mucosal permeability by upregulating TJ-associated proteins (ZO-1, Occludin, Claudin-1, and JAM-A) and downregulating MLCK, thereby repairing intestinal mucosal barrier damage induced by dual induction of antibiotics and LPS. Moreover, ZG suppressed the TLR4/NF-κB signaling pathway, demonstrating anti-inflammatory properties and preserving barrier integrity. Furthermore, ZG restored gut microbiota diversity and richness, evidenced by increased Shannon and Observed features indices, and decreased Simpson's index. ZG also modulated the relative abundance of beneficial human gut bacteria (Bacteroidetes, Firmicutes, Verrucomicrobia, Parabacteroides, Lactobacillus, and Akkermansia) and harmful bacteria (Proteobacteria and Enterobacter), repairing the damage induced by dual administration of antibiotics and LPS. Conclusion: ZG attenuates the dual induction of antibiotics and LPS-induced intestinal barrier damage and also protects the intestinal barrier function in mice.

High-throughput single biomarker identification using droplet nanopore.

Biomarkers are present in various metabolism processes, demanding precise and meticulous analysis at the single-molecule level for accurate clinical diagnosis. Given the need for high sensitivity, biological nanopore have been applied for single biomarker sensing. However, the detection of low-volume biomarkers poses challenges due to their low concentrations in dilute buffer solutions, as well as difficulty in parallel detection. Here, a droplet nanopore technique is developed for low-volume and high-throughput single biomarker detection at the sub-microliter scale, which shows a 2000-fold volume reduction compared to conventional setups. To prove the concept, this nanopore sensing platform not only enables multichannel recording but also significantly lowers the detection limit for various types of biomarkers such as angiotensin II, to 42 pg. This advancement enables direct biomarker detection at the picogram level. Such a leap forward in detection capability positions this nanopore sensing platform as a promising candidate for point-of-care testing of biomarker at single-molecule level, while substantially minimizing the need for sample dilution.

Assessing health risks from bioaccessible PM2.5-bound toxic metals in Nanchang metro: Implications for metro workers and emissions control.

High concentrations of PM2.5 with enriched levels of metallic constituents could significantly affect the health and comfort of metro employees. To avoid overestimating the exposure risks, we investigated the bioaccessibility of toxic metals (TMs) bound in PM2.5 from the Nanchang metro using Gamble's solution method, and qualitatively analyzed the impact of valence state and various sources on the bioaccessibility of TMs bound to PM2.5. The results showed that the bioaccessibility of the studied TMs ranged from 2.1% to 88.1%, with As, Ba, Co and Pb being the most bioaccessible and V, Fe and Cr being the less bioaccessible. The bioaccessibility of TMs in our subway PM2.5 samples varied based on their valence and species, showing higher valence states associated with increased bioaccessibility. Vehicle traffic, secondary aerosols and wheel/rail sources were found to be significantly and positively associated with the bioaccessibility of several TMs, implying a severe potential risk from these three sources. Although both non-carcinogenic and carcinogenic risks associated with total TMs were found to be high, only As and Cr(VI) posed a considerable carcinogenic risk to metro workers based on the bioaccessible fractions and were therefore priority pollutants. In addition, potential carcinogenic risk was found to be more severe in platform than that in ticket counter. The results indicate that considerable efforts are required to control and manage PM2.5 and the associated TMs in the Nanchang subway, particularly from traffic, wheel/rail and secondary sources, to protect the health of metro staff and the public.

Novel therapeutic regimens against Helicobacter pylori: an updated systematic review.

Helicobacter pylori (H. pylori) is a strict microaerophilic bacterial species that exists in the stomach, and H. pylori infection is one of the most common chronic bacterial infections affecting humans. Eradicating H. pylori is the preferred method for the long-term prevention of complications such as chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. However, first-line treatment with triple therapy and quadruple therapy has been unable to cope with increasing antibacterial resistance. To provide an updated review of H. pylori infections and antibacterial resistance, as well as related treatment options, we searched PubMed for articles published until March 2024. The key search terms were "H. pylori", "H. pylori infection", "H. pylori diseases", "H. pylori eradication", and "H. pylori antibacterial resistance." Despite the use of antimicrobial agents, the annual decline in the eradication rate of H. pylori continues. Emerging eradication therapies, such as the development of the new strong acid blocker vonoprazan, probiotic adjuvant therapy, and H. pylori vaccine therapy, are exciting. However, the effectiveness of these treatments needs to be further evaluated. It is worth mentioning that the idea of altering the oxygen environment in gastric juice for H. pylori to not be able to survive is a hot topic that should be considered in new eradication plans. Various strategies for eradicating H. pylori, including antibacterials, vaccines, probiotics, and biomaterials, are continuously evolving. A novel approach involving the alteration of the oxygen concentration within the growth environment of H. pylori has emerged as a promising eradication strategy.

Minimizing Contact Resistance and Flicker Noise in Micro Graphene Hall Sensors Using Persistent Carbene Modified Gold Electrodes.

Scalable micro graphene Hall sensors (µGHSs) hold tremendous potential for highly sensitive and label-free biomagnetic sensing in physiological solutions. To enhance the performance of these devices, it is crucial to optimize frequency-dependent flicker noise to reduce the limit of detection (LOD), but it remains a great challenge due to the large contact resistance at the graphene-metal contact. Here we present a surface modification strategy employing persistent carbene on gold electrodes to reduce the contact resistivity by a factor of 25, greatly diminishing µGHS flicker noise by a factor of 1000 to 3.13 × 10-14 V2/Hz while simultaneously lowering the magnetic LOD SB1/2 to 1440 nT/Hz1/2 at 1 kHz under a 100 µA bias current. To the best of our knowledge, this represents the lowest SB1/2 reported for scalable µGHSs fabricated through wafer-scale photolithography. The reduction in contact noise is attributed to the π-π stacking interaction between the graphene and the benzene rings of persistent carbene, as well as the decrease in the work function of gold as confirmed by Kelvin Probe Force Microscopy. By incorporating a microcoil into the µGHS, we have demonstrated the real-time detection of superparamagnetic nanoparticles (SNPs), achieving a remarkable LOD of ∼528 µg/L. This advancement holds great potential for the label-free detection of magnetic biomarkers, e.g., ferritin, for the early diagnosis of diseases associated with iron overload, such as hereditary hemochromatosis (HHC).

Essential oils as promising treatments for treating Candida albicans infections: research progress, mechanisms, and clinical applications.

Candida albicans: (C. albicans) is a prevalent opportunistic pathogen that can cause severe mucosal and systemic fungal infections, leading to high morbidity and mortality rates. Traditional chemical drug treatments for C. albicans infection have limitations, including the potential for the development of drug resistance. Essential oils, which are secondary metabolites extracted from plants, have gained significant attention due to their antibacterial activity and intestinal regulatory effects. It makes them an ideal focus for eco-friendly antifungal research. This review was aimed to comprehensively evaluate the research progress, mechanisms, and clinical application prospects of essential oils in treating C. albicans infections through their antibacterial and intestinal regulatory effects. We delve into how essential oils exert antibacterial effects against C. albicans infections through these effects and provide a comprehensive analysis of related experimental studies and clinical trials. Additionally, we offer insights into the future application prospects of essential oils in antifungal therapy, aiming to provide new ideas and methods for the development of safer and more effective antifungal drugs. Through a systematic literature review and data analysis, we hope to provide insights supporting the application of essential oils in antifungal therapy while also contributing to the research and development of natural medicines. In the face of increasingly severe fungal infections, essential oils might emerge as a potent method in our arsenal, aiding in the effective protection of human and animal health.

A Novel EWOD Platform for Freely Transporting Droplets in Double and Single-Plate Structures.

This study developed a novel dielectric wetting microfluidic operation platform combining parallel-plate and coplanar-plate regions with a curved surface structure as the connection structure. With the new electrowetting on dielectric (EWOD) platform, "droplet pull-out" has been successfully achieved and viewed as an essential new operation for microfluidics with the dielectric wetting technique. The EWOD system is divided into a PDMS substrate top plate and an indium tin oxide (ITO) glass substrate as a bottom layer on this chip. In the parallel-plate region, the droplets can be generated and transported through the square parallel electrodes; in the single-plate area, the droplets can be pulled out from the parallel structure, transported and mixed through the common grounded coplanar electrodes. In dielectric wetting performance testing, coplanar electrodes can apply a maximum driving force of 31.22 µN to DI water and 13.38 µN to propylene carbonate (PC). This driving force is sufficient to detach the sample from the top cover and pull the sub-droplet from the parallel plate structure for DI water, PC and polyethylene glycol diacrylate (PEGDA) buffer. The novel EWOD system also possesses the advantage of precise volume control for liquid samples; the volume error of the generated droplet can be controlled within 0.1% to 2%.

Protective effects of curcumin on corneal endothelial cell PANoptosis and monocyte adhesion induced by tumor necrosis factor-alpha and interferon-gamma in rats.

Decrease of human corneal endothelial cell (CEC) density leads to corneal edema, progressive corneal opacity, and reduced visual acuity. A reduction in CEC density may be related to elevated levels of inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interferon (INF)-γ. PANoptosis, characterized by the activation of apoptosis, necroptosis, and pyroptosis, could be a factor in the loss of CECs driven by TNF-α and INF-γ. Cytokines also stimulate monocytes adhesion to endothelium. It has been shown in previous research that curcumin plays protective roles against numerous corneal inflammatory diseases. However, it is not determined whether curcumin acts as an anti-PANoptotic agent or if it mitigates monocyte adhesion to CECs. Therefore, this research aimed to explor the potential therapeutic effects of curcumin and its underlying mechanisms in the loss of CECs. CEC injury models were established, and curcumin was injected subconjunctivally. Clinical evaluation of the corneas was conducted using a scoring system and anterior segment photography. Corneal observation was performed with hematoxylin and eosin staining and immunostaining of zona occludens-1(ZO-1). Apoptotic cells within the corneal endothelium were observed using TUNEL staining. The detection of primary proteins expression was accomplished through Western blot analysis. Interleukin (IL)-1ß and macrophage chemotactic protein 1 (MCP-1) levels were determined via ELISA, while the expression of cleaved caspase-3, gasdermin-D (GSDMD), phosphor-mixed lineage kinase domain-like protein (p-MLKL) and intercellular cell adhesion molecule-1 were confirmed by immunofluorescence. Myeloperoxidase (MPO) activity was measured in aqueous humors. Curcumin treatment attenuated the loss of CECs and corneal edema caused by TNF-α and IFN-γ. Besides, it decreased the count of TUNEL-positive cells, and inhibited the upregulation of cleaved caspase-3, cleaved caspase-6, cleaved caspase-7, and cleaved poly (ADP-ribose) polymerase. Moreover, both the expression and phosphorylation of MLKL and receptor-interacting protein 3 were decreased in curcumin-treated rats. Furthermore, curcumin also lowered the expression of cleaved caspase-1, diminished the levels of IL1ß and MCP-1, and inhibited the activity of MPO. Besides, the expression of intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, as well as the number of CD11b-positive cells adhered to the CECs decreased for the administration of curcumin.

Unlocking Mixed-Metal Oxides Active Centers via Acidity Regulation for K&SO2 Poisoning Resistance: Self-Detoxification Mechanism of Zeolite-Confined deNOx Catalysts.

Selective catalytic reduction of nitrogen oxides (NOx) with ammonia (NH3-SCR) is an efficient NOx reduction strategy, while the denitrification (deNOx) catalysts suffer from serious deactivation due to the coexistence of multiple poisoning substances, such as alkali metal (e.g., K), SO2, etc., in industrial flue gases. It is essential to understand the interaction among various poisons and their effects on the deNOx process. Herein, the ZSM-5 zeolite-confined MnSmOx mixed (MnSmOx@ZSM-5) catalyst exhibited better deNOx performance after the poisoning of K, SO2, and/or K&SO2 than the MnSmOx and MnSmOx/ZSM-5 catalysts, the deNOx activity of which at high temperature (H-T) increased significantly (>90% NOx conversion in the range of 220-480 °C). It has been demonstrated that K would occupy both redox and acidic sites, which severely reduced the reactivity of MnSmOx/ZSM-5 catalysts. The most important, K element is preferentially deposited at -OH on the surface of ZSM-5 carrier due to the electrostatic attraction (-O-K). As for the K&SO2 poisoning catalyst, SO2 preferred to be combined with the surface-deposited K (-O-K-SO2ads) according to XPS and density functional theory (DFT) results, the poisoned active sites by K would be released. The K migration behavior was induced by SO2 over K-poisoned MnSmOx@ZSM-5 catalysts, and the balance of surface redox and acidic site was regulated, like a synergistic promoter, which led to K-poisoning buffering and activity recovery. This work contributes to the understanding of the self-detoxification interaction between alkali metals (e.g., K) and SO2 on deNOx catalysts and provides a novel strategy for the adaptive use of one poisoning substance to counter another for practical NOx reduction.