Metabolomic profiling of serum and tongue coating of pregnant women with intrahepatic cholestasis in pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of cesarean section and adverse fetal outcomes. Currently, ICP diagnosis depends largely on serum levels of bile acids and lacks sensitivity and specificity for accurate diagnosis. Tongue diagnosis is an important diagnostic tool in traditional Chinese medicine (TCM) and is used in our clinic as complementary treatment and personalized medicine for ICP. However, the molecular basis of the manifestation of greasy white tongue coatings in ICP remains unknown. In this study, we performed untargeted metabolomic profiling of the serum, tongue coating, and saliva of 66 pregnant women, including 22 with ICP. The metabolomic profiles of the serum and tongue coatings showed marked differences between the two clinical groups. Forty-six differentially abundant metabolites were identified, and their relative concentrations correlated with total bile acid levels. These differential metabolites included bile acids, lipids, microbiota- and diet-related metabolites, and exposomes. Conventional biochemical markers, including serum aminotransferases and bilirubin, were not significantly increased in the ICP group, whereas the total cholesterol and triglyceride levels were significantly increased as early as the first trimester. Our data provide insights into the pathophysiology of ICP and implicate the gut-liver axis and environmental exposure. Tongue coating has the potential to be a non-invasive diagnostic approach. Further studies are required to validate the clinical utility of these findings.

Electrospun of functionalized mesoporous UiO-66 as the selective coating of solid phase microextraction Arrow for the determination of nine alkylphenols.

A solid-phase microextraction (SPME) Arrow and high-performance liquid chromatography-UV detector (HPLC-UV, detection at 225 nm) based method was developed for the selective determination of nine alkylphenols (APs) in milk. The functionalized mesoporous UiO-66 (4-meso-UiO-66) was utilized as the new coating material, which was synthesized by post-modification of pore-expanded UiO-66-NH2 by an esterification reaction with 4-pentylbenzoic acid. It was fully characterized by X-ray photoelectron spectroscopy (XPS), fourier transformation infrared spectrometry, nitrogen sorption-desorption test, scanning electron microscopy, transmission electron microscopy, and X-ray diffractometer. The characterization results showed the ester groups and benzene rings were introduced into the 4-meso-UiO-66, and the mesoporous structure was predominant in the 4-meso-UiO-66. The extraction mechanism of 4-meso-UiO-66 to APs is the synergistic effect of Zr-O electrostatic interaction and the size exclusion effect resulting from XPS, selectivity test, and nitrogen sorption-desorption test. The electrospinning technique was utilized to fabricate the 4-meso-UiO-66 coated SPME Arrow and polyacrylonitrile (PAN) was used as the adhesive. The mass rate of 4-meso-UiO-66 to PAN and the electrospinning time were evaluated. The extraction and desorption parameters were also studied. The linear range of this method was 0.2-1000 µg L-1 with a coefficient of determination greater than 0.9989 under the optimal conditions. The detection limits were 0.05-1 µg L-1, the inter-day and intra-day precision (RSD) were 2.8-11.5%, and the recovery was 83.6%-112%. The reusability study showed that the extraction performance of this new SPME Arrow could be maintained after 80 adsorption-desorption cycles. This method showed excellent applicability for the selective determination of APs in milk.

Use of consecutive transcutaneous oxygen measurement when assessing the need for revascularization and association with the outcomes of ischemic diabetic ulcers.

This study compared the ankle-brachial index (ABI) with transcutaneous oxygen pressure (TcPO2 ) in assessing peripheral vascular disease (PVD) prevalence in 100 diabetic foot ulcer (DFU) patients. Patients were categorized into vascular or nonvascular reconstruction groups and underwent both ABI and TcPO2 measurements four times over 6 months. Predictive validity for PVD diagnosis was analysed using the area under the receiver-operating characteristic curve (AUC). The study found TcPO2 to be a superior predictor of PVD than ABI. Among the DFU patients, 51 with abnormal TcPO2 values underwent vascular reconstruction. Only TcPO2 values showed significant pretreatment differences between the groups and increased post-reconstruction. These values declined over a 6-month follow-up, whereas ABI values rose. For those with end-stage renal disease (ESRD), TcPO2 values saw a sharp decrease within 3 months. Pre-reconstruction TcPO2 was notably lower in amputation patients versus limb salvage surgery patients. In conclusion, TcPO2 is more effective than ABI for evaluating ischemic limb perfusion and revascularization necessity. It should be prioritized as the primary follow-up tool, especially for ESRD patients.

Early identification of delayed wound healing in complex diabetic foot ulcers treated with a dermal regeneration template: a novel clinical target and its risk factors.

BACKGROUND: The dermal regeneration template (DRT), a tissue-engineered skin substitute composing a permanent dermal matrix and an upper temporary silicone layer that serves as the epidermis, has demonstrated efficacy in treating uncomplicated diabetic foot ulcers (DFUs). Our institution has obtained good outcomes with DRT in patients with more complicated DFUs. Because of its chronicity, the authors are working to identify a clinical target that anticipates delayed healing early in the treatment in addition to determining the risk factors linked to this endpoint to increase prevention. MATERIALS AND METHODS: This retrospective single-center study analyzed patients with DFUs who underwent wound reconstruction using DRT between 2016 and 2021. The patients were categorized into poor or good graft-take groups based on their DRT status on the 21st day after the application. Their relationship with complete healing (CH) rate at day 180 was analyzed. Variables were collected for risk factors for poor graft take at day 21. Independent risk factors were identified after multivariable analysis. The causes of poor graft take were also reported. RESULTS: This study examined 80 patients (38 and 42 patients in the poor and good graft-take groups, respectively). On day 180, the CH rate was 86.3% overall, but the poor graft-take group had a significantly lower CH rate (76.3 vs. 95.2%, P =0.021) than the good graft-take group. Our analysis identified four independent risk factors: transcutaneous oxygen pressure less than 30 mmHg (odds ratio, 154.14), off-loading device usage (0.03), diabetic neuropathy (6.51), and toe wound (0.20). The most frequent cause of poor graft take was infection (44.7%), followed by vascular compromise (21.1%) and hematoma (15.8%). CONCLUSION: Our study introduces the novel concept of poor graft take at day 21 associated with delayed wound healing. Four independent risk factors were identified, which allows physicians to arrange interventions to mitigate their effects or select patients more precisely. DRT represents a viable alternative to address DFUs, even in complicated wounds. A subsequent split-thickness skin graft is not always necessary to achieve CH.

Layered metal sulfides with MaSbc- framework (M = Sb, In, Sn) as ion exchangers for the removal of Cs(â ) and Sr(â ¡) from radioactive effluents: a review.

Nuclear power has emerged as a pivotal contributor to the global electricity supply owing to its high efficiency and low-carbon characteristics. However, the rapid expansion of the nuclear industry has resulted in the production of a significant amount of hazardous effluents that contain various radionuclides, such as 137Cs and 90Sr. Effectively removing 137Cs and 90Sr from radioactive effluents prior to discharge is a critical challenge. Layered metal sulfides exhibit significant potential as ion exchangers for the efficient uptake of Cs+ and Sr2+ from aqueous solutions owing to their open and exchangeable frameworks and the distinctive properties of their soft S2- ligands. This review provides a detailed account of layered metal sulfides with MaSb c- frameworks (M = Sb, In, Sn), including their synthesis methods, structural characteristics, and Cs+ and Sr2+ removal efficiencies. Furthermore, we highlight the advantages of layered metal sulfides, such as their relatively high ion exchange capacities, broad active pH ranges, and structural stability against acid and radiation, through a comparative evaluation with other conventional ion exchangers. Finally, we discuss the challenges regarding the practical application of layered metal sulfides in radionuclide scavenging.

Synthesis and Evaluation of Alginate-Based Nanogels as Sustained Drug Carriers for Caffeine.

The objective of this study is to design a polymeric network of nanogels for sustained release of caffeine. Therefore, alginate-based nanogels were fabricated by a free-radical polymerization technique for the sustained delivery of caffeine. Polymer alginate was crosslinked with monomer 2-acrylamido-2-methylpropanesulfonic acid by crosslinker N',N'-methylene bisacrylamide. The prepared nanogels were subjected to sol-gel fraction, polymer volume fraction, swelling, drug loading, and drug release studies. A high gel fraction was seen with the increasing feed ratio of polymer, monomer, and crosslinker. Greater swelling and drug release were observed at pH 4.6 and 7.4 as compared to pH 1.2 due to the deprotonation and protonation of functional groups of alginate and 2-acrylamido-2-methylpropanesulfonic acid. An increase was observed in swelling, loading, and release of the drug with the incorporation of a high feed ratio of polymer and monomer, while a reduction was seen with the increase in crosslinker feed ratio. Similarly, an HET-CAM test was used to evaluate the safety of the prepared nanogels, which showed that the prepared nanogels have no toxic effect on the chorioallantoic membrane of fertilized chicken eggs. Similarly, different characterizations techniques such as FTIR, DSC, SEM, and particle size analysis were carried out to determine the development, thermal stability, surface morphology, and particle size of the synthesized nanogels, respectively. Thus, we can conclude that the prepared nanogels can be used as a suitable agent for the sustained release of caffeine.

A Method to Replace NaCl as a Flotation Solution for Extracting MPs in Soil: A Case Study of the Jiaxing Agricultural Soil from China.

Microplastics (MPs) have become an important global issue in recent years. However, MPs in the soil have received far less attention than water. Effective and nondestructive extraction of MPs is important for studying MPs in agricultural soils. This study uses different floatation solutions as experiments and uses MgCl2 as the floatation solution of the density extraction method. Five types of standard MPs (PE, PP, PS, PVC, and PET) are used as the objects of this experiment. The recovery of the two particle sizes was between 90.82% and 109.69%. The extracted standard MPs were then subjected to IR and Raman spectroscopic analysis, and the results showed that Raman spectroscopy was more suitable for the identification of the extracted MPs. Finally, this method collected and verified a vast number of soil samples and further analyzed the abundance and characteristics of the collected MPs.

A practical multicellular sample preparation pipeline broadens the application of in situ cryo-electron tomography.

The structural studies of macromolecules in their physiological context, particularly in tissue, is constrained by the bottleneck of sample preparation. In this study, we present a practical pipeline for preparing multicellular samples for cryo-electron tomography. The pipeline comprises sample isolation, vitrification, and lift-out-based lamella preparation using commercially available instruments. We demonstrate the efficacy of our pipeline by visualizing pancreatic ß cells from mouse islets at the molecular level. This pipeline enables the determination of the properties of insulin crystals in situ for the first time, using unperturbed samples.

Higher ecological risks and lower bioremediation potentials identified for emerging OPEs than legacy PCBs in the Beibu Gulf, China.

The production and use of organophosphate esters (OPEs) as substitutes for traditional halogenated flame retardants is increasing, resulting in greater global concern related to their ecological risks to marine environments. In this study, polychlorinated biphenyls (PCBs) and OPEs, representing traditional halogenated and emerging flame retardants, respectively, were studied in multiple environmental matrices in the Beibu Gulf, a typical semi-closed bay in the South China Sea. We investigated the differences in PCB and OPE distributions, sources, risks, and bioremediation potentials. Overall, the concentrations of emerging OPEs were much higher than those of PCBs in both seawater and sediment samples. Sediment samples from the inner bay and bay mouth areas (L sites) accumulated more PCBs, with penta- and hexa-CBs as major homologs. Chlorinated OPEs were prevalent in both seawater and sediment samples from the L sites, whereas tri-phenyl phosphate (TPHP) and tri-n-butyl phosphate (TNBP) were predominant at the outer bay (B sites) sediment samples. Source identification via principal component analysis, land use regression statistics, and δ13C analysis indicate that PCBs were mainly sourced from the atmospheric deposition of sugarcane and waste incineration, whereas sewage inputs, aquaculture, and shipping activity were identified as sources of OPE pollution in the Beibu Gulf. A half-year sediment anaerobic culturing experiment was performed for PCBs and OPEs, and the results only exhibited satisfactory dechlorination for PCBs. However, compared with the low ecological risks of PCBs to marine organisms, OPEs (particularly trichloroethyl phosphate (TCEP) and TPHP) exhibited low to medium threats to algae and crustaceans at most sites. Given their increasing usage, high ecological risks, and low bioremediation potential in enrichment cultures, pollution by emerging OPEs warrants close attention.

Nanoplastics exposure disrupts circadian rhythm associated with dysfunction of the endolysosomal pathway and autophagy in Caenorhabditis elegans.

Nanoplastics (NPs), an emerging pollutant, have raised great safety concerns due to their widespread applications and continuous release into the environment, which lead to potential human and environmental risks. Recently, polystyrene NPs (100 nm; 100 mg/L) exposure has been reported to disrupt circadian rhythms under five days temperature entrainment and be associated with stress resistance decline in Caenorhabditis elegans. This study explored the possible relationship between circadian rhythm disruption and endocytosis and autophagy under polystyrene NPs exposure in C. elegans. We show that the disrupted circadian rhythm induced by NPs exposure reduced stress resistance via endocytosis and autophagy impairment. Furthermore, we found that most NPs taken up by intestinal cells were localized to early endosomes, late endosomes, and lysosomes and delivered to autophagosomes. In addition, the disruption of circadian rhythm inhibited NPs localization to these organelles. These findings indicate that NPs exposure disrupts circadian rhythm and alters its subcellular trafficking, leading to enhanced toxicity in C. elegans. Our results shed light on the prominent role of NPs exposure in circadian rhythm disruption associated with endocytosis and autophagy impairments, which may be conserved in higher animals such as humans.

Multidisciplinary Strategies With Real-Time Fluorescence Images and Negative Pressure Wound Therapy to Manage Organ/Space Surgical Site Infection in Transplanted Kidneys.

BACKGROUND: Surgical site infection (SSI) after kidney transplantation can severely compromise graft function and prolong hospital stay. Organ/space SSI (osSSI) is a severe type of SSI associated with a significantly higher mortality rate. AIMS AND OBJECTIVES: This study aims to provide new strategies of managing (osSSI) after kidney transplant and other high-risk wound infections. METHOD: This is a single-center, retrospective study that analyzed the treatment outcomes of 4 patients who developed osSSI after kidney transplant at Shuang-Ho Hospital. The management strategy included real-time fluorescence imaging with MolecuLight, negative-pressure wound therapy (NPWT) with Si-Mesh, and incisional NPWT (iNPWT). RESULT: The average length of hospital stay was 18 days (range, 12-23 days). During hospitalization, all patients obtained high-quality debridement under real-time fluorescence image confirmation. The average duration of NPWT was 11.8 days (range, 7-17 days) and iNPWT was 7 days. All transplanted kidneys were preserved with normal function after 6 months of follow-up. CONCLUSIONS: Our strategies with real-time fluorescence imaging provide a novel and effective method that can be used in adjunct with the standard of care for managing osSSI after kidney transplantation. More studies are warranted to validate the efficacy of our approach.

Multifunctional Nano-Realgar Hydrogel for Enhanced Glioblastoma Synergistic Chemotherapy and Radiotherapy: A New Paradigm of an Old Drug.

Purpose: Realgar, as a kind of traditional mineral Chinese medicine, can inhibit multiple solid tumor growth and serve as an adjuvant drug in cancer therapy. However, the extremely low solubility and poor body absorptive capacity limit its application in clinical medicine. To overcome this therapeutic hurdle, realgar can here be fabricated into a nano-realgar hydrogel with enhanced chemotherapy and radiotherapy (RT) ability. Our objective is to evaluate the superior biocompatibility and anti-tumor activity of nano-realgar hydrogel. Methods: We have successfully synthesized nano-realgar quantum dots (QDs) coupling with 6-AN molecules (NRA QDs) and further encapsulated with a pH-sensitive dextran hydrogel carrier with hyaluronic acid coating (DEX-HA gel) to promote bioavailability, eventually forming a multifunctional nano-realgar hydrogel (NRA@DH Gel). To better investigate the tumor therapy efficiency of the NRA@DH Gel, we have established the mice in situ bearing GL261 brain glioblastoma as animal models assigned to receive intratumor injection of NRA@DH Gel. Results: The designed NRA@DH Gel as an antitumor drug can not only exert the prominent chemotherapy effect but also as a "sustainable reactive oxygen species (ROS) generator" can inhibit in the pentose phosphate pathway (PPP) metabolism and reduce the production of nicotinamide adenine dinucleotide phosphate (NADPH), thereby inhibiting the conversion of glutathione disulfide (GSSG) to glutathione (GSH), reducing GSH concentrations in tumor cells, triggering the accumulation of ROS, and finally enhancing the effectiveness of RT. Conclusion: Through the synergistic effect of chemotherapy and RT, NRA@DH Gel effectively inhibited the proliferation and migration of tumor cells, suppressed tumor growth, improved motor coordination, and prolonged survival in tumor-bearing mice. Our work aims to improve the NRA@DH Gel-mediated synergistic chemotherapy and RT will endow a "promising future" for the old drug in clinically comprehensive applications.

Multiomic characterization and drug testing establish circulating tumor cells as an ex vivo tool for personalized medicine.

Matching the treatment to an individual patient's tumor state can increase therapeutic efficacy and reduce tumor recurrence. Circulating tumor cells (CTCs) derived from solid tumors are promising subjects for theragnostic analysis. To analyze how CTCs represent tumor states, we established cell lines from CTCs, primary and metastatic tumors from a mouse model and provided phenotypic and multiomic analyses of these cells. CTCs and metastatic cells, but not primary tumor cells, shared stochastic mutations and similar hypomethylation levels at transcription start sites. CTCs and metastatic tumor cells shared a hybrid epithelial/mesenchymal transcriptome state with reduced adhesive and enhanced mobilization characteristics. We tested anti-cancer drugs on tumor cells from a metastatic breast cancer patient. CTC responses mirrored the impact of drugs on metastatic rather than primary tumors. Our multiomic and clinical anti-cancer drug response results reveal that CTCs resemble metastatic tumors and establish CTCs as an ex vivo tool for personalized medicine.

SQEIR: An epidemic virus spread analysis and prediction model.

In 2019, a new strain of coronavirus pneumonia spread quickly worldwide. Viral propagation may be simulated using the Susceptible Infectious Removed (SIR) model. However, the SIR model fails to consider that separation of patients in the COVID-19 incubation stage entails difficulty and that these patients have high transmission potential. The model also ignores the positive effect of quarantine measures on the spread of the epidemic. To address the two flaws in the SIR model, this study proposes a new infectious disease model referred to as the Susceptible Quarantined Exposed Infective Removed (SQEIR) model. The proposed model uses the weighted least squares for the optimal estimation of important parameters in the infectious disease model. Based on these parameters, new differential equations were developed to describe the spread of the epidemic. The experimental results show that this model exhibits an accuracy 6.7% higher than that of traditional infectious disease models.

C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8.

Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. The aECM is highly dynamic and constantly undergoes remodeling during animal development. How aECM dynamics is temporally regulated during development, and whether and how its mis-regulation may impact epidermal cell morphology or function remains to be fully elucidated. Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. The apical epidermal morphological defect is suppressed by reduction of bus-8 or mlt-8. BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. MLT-8::GFP fusion protein is localized to lysosomes and secreted to aECM. BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition.

Effect of propiconazole on plastic film microplastic degradation: Focusing on the change in microplastic morphology and heavy metal distribution.

With the rapid increase in the use of plastic films, microplastic (MP) pollution in agricultural soils has become a global environmental problem. Propiconazole is widely used in agriculture and horticulture; however, its role in plastic film degradation remains elusive. Butylene adipate-co-terephthalate (PBAT) and polyethylene (PE) films were used to analyze the effects of propiconazole on plastic film and MP degradation. We identified the surface morphologies of PBAT and PE at different propiconazole concentrations and soil pH values, as well as the adsorption and release characteristics of heavy metals during the degradation process via scanning electron microscopy, Fourier transform infrared spectroscopy and inductively coupled plasma mass spectrometry. Propiconazole accelerated the degradation of MPs, adsorption of heavy metals (Ni and Zn), and release of Sn at low concentrations (≤40 mg/kg); however, these effects were evidently absent at a high concentration (120 mg/kg). Furthermore, MPs were more prone to degradation in acidic or alkaline soils than in neutral soil when they coexisted with propiconazole. Hence, we suggest that PBAT and PE plastic films may not be suitable for application in acidic and alkaline soils with propiconazole, because of shorter rupture time and more heavy metal adsorption. PBAT degraded faster, absorbed and released more heavy metals than PE. Under all tested conditions, the heavy metal contents in MPs gradually approached those in soil, which proves that MPs are carriers of heavy metal pollutants. These results may help in assessing the impact of MPs on soil environments and provide a theoretical basis for the standardized propiconazole and plastic film usage.

FLT4/VEGFR3 activates AMPK to coordinate glycometabolic reprogramming with autophagy and inflammasome activation for bacterial elimination.

Macrophages rapidly undergo glycolytic reprogramming in response to macroautophagy/autophagy, inflammasome activation and pyroptosis for the clearance of bacteria. Identification the key molecules involved in these three events will provide critical potential therapeutic applications. Upon S. typhimurium infection, FLT4/VEGFR3 and its ligand VEGFC were inducibly expressed in macrophages, and FLT4 signaling inhibited CASP1 (caspase 1)-dependent inflammasome activation and pyroptosis but enhanced MAP1LC3/LC3 activation for elimination of the bacteria. Consistently, FLT4 mutants lacking the extracellular ligand-binding domain increased production of the proinflammatory metabolites such as succinate and lactate, and reduced antimicrobial metabolites including citrate and NAD(P)H in macrophages and liver upon infection. Mechanistically, FLT4 recruited AMP-activated protein kinase (AMPK) and phosphorylated Y247 and Y441/442 in the PRKAA/alpha subunit for AMPK activation. The AMPK agonist AICAR could rescue glycolytic reprogramming and inflammasome activation in macrophages expressing the mutant FLT4, which has potential translational application in patients carrying Flt4 mutations to prevent recurrent infections. Collectively, we have elucidated that the FLT4-AMPK module in macrophages coordinates glycolytic reprogramming, autophagy, inflammasome activation and pyroptosis to eliminate invading bacteria.Abbreviations: 3-MA: 3-methyladenine; AICAR: 5-aminoimidazole-4-carboxamide1-ß-D-ribofuranoside; AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATP: adenosine triphosphate; BMDM: bone marrow-derived macrophage; CASP1: caspase 1; CFUs: colony-forming units; FLT4/VEGFR3: FMS-like tyrosine kinase 4; GFP: green fluorescent protein; LDH: lactate dehydrogenase; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; PEM: peritoneal exudate macrophage; PRKAA1/AMPKα1: protein kinase, AMP-activated, alpha 1 catalytic subunit; PYCARD/ASC: PYD and CARD domain containing; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TLR4: toll-like receptor 4; ULK1: unc-51 like autophagy activating kinase 1; VEGFC: vascular endothelial growth factor C; WT: wild type.

Early developmental nanoplastics exposure disturbs circadian rhythms associated with stress resistance decline and modulated by DAF-16 and PRDX-2 in C. elegans.

Plastics pollution is an emerging environmental problem and nanoplastics (NPs) toxicity has received great concern. This study investigated whether early developmental exposure to polystyrene NPs influence the circadian rhythms and the possible underlying mechanisms in C. elegans. We show that early developmental NPs exposure disturbs circadian rhythms in C. elegans and ASH neurons and G protein-coupled receptor kinase (GRK-2) are involved in the level of chemotaxis response. A higher bioconcentration factor in entrained worms was observed, suggesting that circadian interference results in increased NPs bioaccumulation in C. elegans. In addition, we show that reactive oxygen species produced by NPs exposure and peroxiredoxin-2 (PRDX-2) are related to the disturbed circadian rhythms. We further show that the NPs-induced circadian rhythms disruption is associated with stress resistance decline and modulated by transcription DAF-16/FOXO signaling. Because circadian rhythms are found in most living organisms and the fact that DAF-16 and PRDX-2 are evolutionarily conserved, our findings suggest a possible negative impact of NPs on circadian rhythms and stress resistance in higher organisms including humans.

Development of a water refractive index-matched microneedle integrated into a light sheet microscopy system for continuous embryonic cell imaging.

In this study, microneedle-integrated light sheet microscopy (LSM) was developed for trapping and continuously imaging embryos of Caenorhabditis elegans with subcellular resolution. To reduce aberrations when the light sheet was propagated into the device, a microneedle was fabricated using a transparent, water refractive index-matched polymer. It was proven that when the light sheet emerged from the water-immersed objective and penetrated through the microneedle with a circular surface, even with a non-perpendicular incident angle, fewer aberrations were found. An embryo was injected into and trapped at the tip of the microneedle, which was positioned at the interrogation window of the LSM apparatus with the image plane perpendicular to the light sheet, and this setup was used to sequentially acquire embryo images. By applying the light sheet, higher-resolution, higher-contrast images were obtained. The system also showed low photobleaching and low phototoxicity to embryos of C. elegans. Furthermore, three-dimensional embryo images with a whole field of view of the microneedle could be achieved by stitching together images and reconstructing sequential two-dimensional embryo images.

Ultrasensitive Detection of Alzheimer's Amyloids on a Plasmonic-Gold Platform.

More than 55 million people live with dementia worldwide in 2021, and there are nearly 10 million new cases every year. Alzheimer's disease (AD) is the most common cause of dementia. Despite urgent need, early detection of AD and long-term monitoring of AD progression have been challenging. This is due to the limited availability of brain imaging facilities and the highly invasive procedure with the cerebrospinal fluid assay to assess the level of AD biomarkers, such as beta-amyloid (Aß). Reliable measurements of AD biomarkers in blood samples are still difficult because of their very low abundance. Here, we develop a rapid, specific, and ultrasensitive immunoassay using plasmonic-gold nanoisland (pGOLD) chips with near-infrared fluorescence-enhanced detection for Aß1-40 and Aß1-42. We show step-by-step processes and results during the platform establishment, including antibody specificity and sensitivity tests, antibody pair examination, condition optimization, and procedure refinement. Finally, we demonstrate the platform performance with detection sensitivity at the subpicogram per milliliter level. This platform, therefore, has a great application potential for early detection of AD using blood samples.