Hampshire Sheep as a Large-Animal Model for Cochlear Implantation.

BACKGROUND: Sheep have been proposed as a large-animal model for studying cochlear implantation. However, prior sheep studies report that the facial nerve (FN) obscures the round window membrane (RWM), requiring FN sacrifice or a retrofacial opening to access the middle-ear cavity posterior to the FN for cochlear implantation. We investigated surgical access to the RWM in Hampshire sheep compared to Suffolk-Dorset sheep and the feasibility of Hampshire sheep for cochlear implantation via a facial recess approach. METHODS: Sixteen temporal bones from cadaveric sheep heads (ten Hampshire and six Suffolk-Dorset) were dissected to gain surgical access to the RWM via an extended facial recess approach. RWM visibility was graded using St. Thomas' Hospital (STH) classification. Cochlear implant (CI) electrode array insertion was performed in two Hampshire specimens. Micro-CT scans were obtained for each temporal bone, with confirmation of appropriate electrode array placement and segmentation of the inner ear structures. RESULTS: Visibility of the RWM on average was 83% in Hampshire specimens and 59% in Suffolk-Dorset specimens (p = 0.0262). Hampshire RWM visibility was Type I (100% visibility) for three specimens and Type IIa (> 50% visibility) for seven specimens. Suffolk-Dorset RWM visibility was Type IIa for four specimens and Type IIb (< 50% visibility) for two specimens. FN appeared to course more anterolaterally in Suffolk-Dorset specimens. Micro-CT confirmed appropriate CI electrode array placement in the scala tympani without apparent basilar membrane rupture. CONCLUSIONS: Hampshire sheep appear to be a suitable large-animal model for CI electrode insertion via an extended facial recess approach without sacrificing the FN. In this small sample, Hampshire specimens had improved RWM visibility compared to Suffolk-Dorset. Thus, Hampshire sheep may be superior to other breeds for ease of cochlear implantation, with FN and facial recess anatomy more similar to humans.

Cannabis use and the prevalence of current asthma among adolescents and adults in the United States.

OBJECTIVES: Cannabis use has increased among adolescents and adults in the United States (US) in recent years. Few data are available on the prevalence of asthma by frequency of cannabis use. This study aimed to estimate the prevalence of asthma by frequency of past 30-day cannabis use among US individuals. METHODS: Data were drawn from the 2020 National Survey on Drug Use and Health (NSDUH), a nationally representative, annual cross-sectional survey of US individuals aged 12 and older in the United States (N = 32,893). Logistic regression models were used to examine the relationship between frequency of any cannabis and/or blunt (i.e., cannabis smoked in a hollowed-out cigar) use in the past 30 days and current asthma, adjusting for demographics and current cigarette smoking. RESULTS: Current asthma was more common among US individuals who reported cannabis use in the past 30-days, relative to those who did not (9.8% vs. 7.4%, p < 0.0001). The odds of asthma was significantly greater among individuals reporting cannabis use 20-30 days/month (Adjusted Odds Ratio [AOR] = 1.67, 95% CI:1.21, 2.31), blunt use 6-15 and 20-30 days/month (AOR = 1.9, 95% CI:1.1, 3.2; AOR = 2.2, 95% CI:1.4, 3.6), respectively, than among those without. A positive linear relationship was observed between frequency of a) cannabis use (p < 0.0001) and b) blunt use (p < 0.0001) and current asthma prevalence. CONCLUSIONS: Findings suggest a dose-response relationship between frequency of current cannabis use and the prevalence of current asthma in the US individuals.

Development and Validation of a Propionate Metabolism-Related Gene Signature for Prognostic Prediction of Hepatocellular Carcinoma.

Background: Studies have demonstrated that propionate metabolism-related genes (PMRGs) are associated with cancer progression. PMRGs are not known to be involved in Hepatocellular carcinoma (HCC). Methods: In this study, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were accessed for HCC-related transcriptome data and clinical information. First, DE-PMRGs were derived by intersecting PMRGs and DEGs between HCC tissues and normal controls. The clusterProfiler R package was then used to enrich DE-PMRGs. In addition, biomarkers of HCC were identified, and a prognostic model was developed. Using functional analysis and tumor microenvironment analysis, new insights were obtained into HCC. The expression of biomarkers was validated using quantitative real-time polymerase chain reaction (qRT-PCR). Results: 132 DE-PMRGs were obtained by intersecting 3690 DEGs and 291 PMRGs. Steroid and organic acid metabolism were associated with these genes. For the construction of the risk model for HCC samples, five biomarkers were identified, including Acyl-CoA dehydrogenase short chain (ACADS), CYP19A1, formiminotransferase cyclodeaminase (FTCD), glucose-6-phosphate dehydrogenase (G6PD), and glutamic-oxaloacetic transaminase (GOT2). ACADS, FTCD, and GOT2 were positive factors, whereas CYP19A1 and G6PD were negative. HCC patients with AUC greater than 0.6 were predicted to survive 1/2/3/4/5 years, indicating decent efficiency of the model. The probability of 1/3/5-survival for HCC was also predicted by the nomogram using the risk score, pathologic T stage, and cancer status. Moreover, functional enrichment analysis revealed the high-risk genes were associated with invasion and epithelial-mesenchymal transition. Significantly, immune cell infiltration and immune checkpoint expression were linked to HCC development. Conclusion: This study identified five biomarkers of propionate metabolism that can predict HCC prognosis. This finding may provide a deeper understanding of PMRG function in HCC.

Effect of Strain Rate and Temperature on the Tensile Properties of Long Glass Fiber-Reinforced Polypropylene Composites.

Strain rate and temperature are influential factors that significantly impact the mechanical properties of long glass fiber-reinforced polypropylene composites. This study aims to investigate the tensile properties of these composites, analyzing the effects of temperature, strain rate, and their interplay on variables such as tensile stress, tensile strength, fracture stress, and fracture morphology through a series of comprehensive tensile experiments. The experimental results demonstrate a notable increase in both tensile strength and tensile fracture stress when the temperature is set at 25 °C, accompanied by strain rates of 10-4, 10-3, 10-2, and 10-1 s-1. Conversely, a significant decrease is observed in the aforementioned properties when the strain rate is fixed at 10-4, while varying temperatures of -25 °C, 0 °C, 25 °C, 50 °C, and 75 °C are applied. At lower temperatures, cracks manifest on the fracture surface, while matrix softening occurs at higher temperatures. Additionally, in the context of strain rate-temperature coupling, the decreasing trend of both tensile strength and tensile fracture stress decelerates as the temperature ranges from -25 °C to 75 °C at a strain rate of 10-1, compared to 10-4 s-1. These findings highlight the significant influence of both strain rate and temperature on high fiber content long glass fiber-reinforced polypropylene composites.

Pyrolyzed Ultrasharp Glassy Carbon Microneedles.

Polymeric microneedles fabricated via two-photon polymerization (2PP) lithography enable safe medical access to the inner ear. Herein, the material class for 2PP-lithography-based microneedles is expanded by pyrolyzing 2PP-fabricated polymeric microneedles, resulting in glassy carbon microneedles. During pyrolysis the microneedles shrink up to 81% while maintaining their complex shape when the exposed surface-area-to-volume ratio (SVR) is 0.025 < SVR < 0.04, for the temperature history protocol used herein. The derived glassy carbon is confirmed with energy-dispersive X-ray spectroscopy and Raman spectroscopy. The pyrolyzed glassy carbon has Young's modulus 9.0 GPa. As a brittle material, the strength is stochastic. Using the two-parameter Weibull distribution, the glassy carbon has Weibull modulus of 3.1 and characteristic strength of 710 MPa. The viscoelastic response has characteristic time scale of about 10000 s. In vitro experiments demonstrate that the glassy carbon microneedles introduce controlled perforations across the guinea pig round window membrane (RWM) from the middle ear space into the inner ear, without damaging the microneedle. The resultant controlled perforation of RWM is known to enhance diffusion of therapeutics across the RWM in a predictable fashion. Hence, the glassy carbon microneedles can be deployed for mediating inner ear delivery.

Role of formaldehyde in promoting aromatic selectivity during methanol conversion over gallium-modified zeolites.

Gallium-modified HZSM-5 zeolites are known to increase aromatic selectivity in methanol conversion. However, there are still disputes about the exact active sites and the aromatic formation mechanisms over Ga-modified zeolites. In this work, in situ synchrotron radiation photoionization mass spectrometry (SR-PIMS) experiments were carried out to study the behaviors of intermediates and products during methanol conversion over Ga-modified HZSM-5. The increased formaldehyde (HCHO) yield over Ga-modified HZSM-5 was found to play a key role in the increase in aromatic yields. More HCHO was deemed to be generated from the direct dehydrogenation of methanol, and Ga2O3 in Ga-modified HZSM-5 was found to be the active phase. The larger increase in aromatic production over Ga-modified HZSM-5 after reduction‒oxidation treatment was found to be the result of redispersed Ga2O3 with smaller size generating a larger amount of HCHO. This study provides some new insights into the internal driving force for promoting the production of aromatics over Ga-modified HZSM-5.

Simultaneous surface functionalization and drug loading: A novel method for fabrication of cellulose nanocrystals-based pH responsive drug delivery system.

Herein, a novel strategy for surface functionalization and drug loading of cellulose nanocrystals (CNCs) through formation of hydrazone bonds between functionalized CNCs and aldehyde group containing polyethylene glycol (CHO-PEG)/anticancer drug doxorubicin (DOX) was reported for the first time. DOX could be loaded on PEGylated CNCs with high capacity and released from drug complexes (P-CNCs-D) with pH dependent behavior. The biological evaluation results demonstrated that drug carriers (CNCs-EBO-NH) showed negative cytotoxicity while DOX could be transported into cells and exhibits desirable anticancer effects. As compared with other method, the method developed in this work is rather simple and effective and can be achieved for simultaneous for surface functionalization and drug loading in a one-pot route. This work will open a new avenue for fabrication of various multifunctional composites based on other carbohydrate polymers or materials and to explore their applications in biomedical fields.

Response of rice (Oryza sativa L.) roots to nanoplastic treatment at seedling stage.

Potential adverse effects of nanoplastics (NPs) on marine organisms have received increased attention in recent years. In contrast, few data are available on terrestrial plants, especially on the mechanisms for transport of NPs in plants and phytotoxicity (at both phenotypic and molecular levels) of plants induced by NPs. To address this knowledge gap, we conducted a microcosm study in which hydroponically-cultured rice (Oryza sativa L.) seedlings were exposed to polystyrene (PS)-NPs at 0, 10, 50, and 100 mg L-1 for 16 d and examined for morphological and physiological phenotypes and transcriptomics. Laser confocal scanning micrographs confirmed PS-NPs were uptaken by rice roots, greatly benefitted from the transport activity of aquaporin in rice roots. The significant enhancement (p < 0.05) of antioxidant enzyme activities reflected the oxidative stress response of rice roots upon exposure to PS-NPs. Treatment by PS-NPs decreased root length and increased lateral root numbers. Carbon metabolism was activated (e.g., increased carbon and soluble sugar contents) whereas jasmonic acid and lignin biosynthesis were inhibited. The present study demonstrated the likelihood for transport of PS-NPs in rice roots and induced phytotoxicity by PS-NPs, which should inspire further investigations into the potential human health risks from rice consumption.

PL-S2, a homogeneous polysaccharide from Radix Puerariae lobatae, attenuates hyperlipidemia via farnesoid X receptor (FXR) pathway-modulated bile acid metabolism.

Polysaccharides are important active constituents of Radix Puerariae lobatae (RPL). In this study, a novel homogeneous polysaccharide from RPL was successfully obtained by HP-20 macroporous resin and purified by Sepharose G-100 column chromatography. Nuclear magnetic resonance (NMR) analysis showed that the main glycosidic bonds were composed of α-1,3-linked and α-1,4-linked glucose. The molecular weight of PL-S2 was 18.73 kDa. The hypolipidemic effect of PL-S2 on hyperlipidemic rats was evaluated in histopathology and metabolomics analyses. PL-S2 significantly reduced plasma lipid levels and inhibited bile acid metabolism. We also demonstrated that treatment with PL-S2 activated FXR, CYP7A1, BESP, and MRP2 in rat liver. Our findings first indicate that PL-S2 decreases plasma lipid levels in hyperlipidemic rats by activating the FXR signaling pathway and promoting bile acid excretion. Therefore, PL-S2 derived from RPL is implicated as a functional food factor with lipid-regulating activity, and highlighted as a potential food supplement for the treatment of hyperlipidemia.

Pharmacokinetic and Lipidomic Assessment of the In Vivo Effects of Parishin A-Isorhynchophylline in Rat Migraine Models.

Migraine is a chronic brain disease that leads to periodic neurological attacks. Parishin A and isorhynchophylline (PI) is the active monomer component extracted from the traditional antimigraine Chinese medicinal combination of Gastrodia and Uncaria, respectively. In this study, using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) technology, we performed pharmacokinetic and lipidomic study on migraine model rats after administration of PI. For the detection of the compounds in plasma, AB Sciex Triple Quad™ 4500 was applied for quantitative analysis, and the COSMOSIL C18 column (2.1 × 100 mm, 2.6 µm) was used for separation. Isorhynchophylline (ISO: m/z 384.8-241.2) and its main metabolite rhynchophylline (RHY: m/z 384.8-160.2) were simultaneously detected under positive ion modes. Besides, parishin A (PA: m/z 995.1-726.9) and its main metabolite gastrodin (GAS: m/z 331.1-123.0) were simultaneously detected with negative ion modes. For the analysis of endogenous lipid components, Dionex Ultimate 3000 (UHPLC) Thermo Orbitrap Elite was applied for the detection, and the Waters UPLCRBEH C18 column (1.7 µm 100 ∗ 2.1 mm) was used for separation. Chloroform/methanol (2 : 1, v : v) was used for extraction. The results demonstrated that PI exists significant difference in metabolism between single- and coadministration and can regulate lipid levels associated with migraine.

Formation and Fate of Formaldehyde in Methanol-to-Hydrocarbon Reaction: In Situ Synchrotron Radiation Photoionization Mass Spectrometry Study.

HCHO has been confirmed as an active intermediate in the methanol-to-hydrocarbon (MTH) reaction, and is critical for interpreting the mechanisms of coke formation. Here, HCHO was detected and quantified during the MTH process over HSAPO-34 and HZSM-5 by in situ synchrotron radiation photoionization mass spectrometry. Compared with conventional methods, excellent time-resolved profiles were obtained to study the formation and fate of HCHO, and other products during the induction, steady-state reaction, and deactivation periods. Similar formation trends of HCHO and methane, and their close correlation in yields suggest that they are derived from disproportionation of methanol at acidic sites. In the presence of Y2 O3 , the amount of HCHO changes, affecting the hydrogen-transfer processes of olefins into aromatics and aromatics into cokes. The yield of HCHO affects the aromatic-based cycle and the formation of ethylene, indicating that ethylene is mainly formed from the aromatic-based cycle.

"Two in one": Simultaneous functionalization and DOX loading for fabrication of nanodiamond-based pH responsive drug delivery system.

Nanodiamond (ND) has been widely studied as a new type of carbon nanomaterials that is expected to be used as a promising candidate in various fields especially in the field of biomedicine. However, its poor water dispersibility and insufficient controlled release limit its practical applications. In this paper, ND-based composites with pH-responsive hydrazone bonds were successfully prepared by a simple chemical reaction between ester groups and hydrazine hydrate, in which ester groups were conjugated on the surface of ND via thiol-ene click reaction. On the other hand, CHO-PEG and doxorubicin hydrochloride (DOX) were linked on the carriers through formation of hydrazone bonds, resulting in improving water dispersibility and high drug loading capacity. The structure, thermal stability, surface morphology and particle size of ND carriers were characterized by different equipment. Results demonstrated that we have successfully prepared these functionalized ND. The release rate of DOX in acidic environment was significantly greater than that in normal physiological environment. More importantly, cell viability and optical imaging results showed that ND-based composites possess good biocompatibility, therapeutic effect, and could successfully transport DOX to HepG2 cells. Considering the above results, we believe that our new ND carriers will become promising candidates for intracellular controlled drug delivery and cancer treatment.

One-Dimensional Synergistic Core-Shell Nanozymes with Superior Peroxidase-like Activity for Ultrasensitive Colorimetric Detection of Blood Cholesterol.

In this paper, a simple and green strategy was proposed to fabricate one-dimensional core-shell Fe3O4@C/Ni nanocomposites. The rationally designed hybrid nanostructures notably exhibited an extremely excellent peroxidase-mimicking property, arising from the synergetic effects of Fe3O4, carbon, and Ni nanoparticles, along with the hollow and hierarchically porous nanostructures. Based upon the outstanding peroxidase-like activity and cholesterol oxidase cascade reaction, a label-free, ultrasensitive, and highly selective colorimetric assay for cholesterol determination has been developed. Under the optimized conditions, the colorimetric biosensor demonstrated a linear response to cholesterol ranging from 5 to 200 µM, with a relatively low detection limit of 0.17 µM. More importantly, cholesterol determination as low as 5 µM could be directly distinguished with the naked eye. In addition, we successfully determined the total cholesterol content in human serum samples with satisfactory accuracy and good precision. The Fe3O4@C/Ni nanocatalyst-based colorimetric biosensor provides great potential in point-of-care testing in disease diagnosis.

Online photoionization mass spectrometric evaluation of catalytic co-pyrolysis of cellulose and polyethylene over HZSM-5.

The hydrogen-deficient and oxygen-rich nature of lignocellulosic biomass prohibits effective conversions of biomass to fuels and chemicals via catalytic pyrolysis due to significant coking of the catalysts. Co-feeding of biomass feedstock with hydrogen-rich and oxygen-deficient thermoplastics could improve the process. Herein, thermal and catalytic co-pyrolysis of cellulose and polyethylene (PE) was studied via thermogravimetry combined with an online photoionization time-of-flight mass spectrometry (PI-TOF-MS). No notable synergetic effect was found in the thermal co-pyrolysis process while a considerable synergetic effect was observed during the catalytic co-pyrolysis. In the case of catalytic pyrolysis, co-feeding of cellulose with PE significantly improved the aromatic formation. Detailed reaction intermediates and products were detected by PI-TOF-MS and the process of aromatization could be ascribed to aromatization of small oxygenates and olefins, as well as Diels-Alder reaction and dehydration by HZSM-5. Moreover, this study provides a reliable tool for screening and optimizing of catalytic co-pyrolysis.

Compliant and stretchable thermoelectric coils for energy harvesting in miniature flexible devices.

With accelerating trends in miniaturization of semiconductor devices, techniques for energy harvesting become increasingly important, especially in wearable technologies and sensors for the internet of things. Although thermoelectric systems have many attractive attributes in this context, maintaining large temperature differences across the device terminals and achieving low-thermal impedance interfaces to the surrounding environment become increasingly difficult to achieve as the characteristic dimensions decrease. Here, we propose and demonstrate an architectural solution to this problem, where thin-film active materials integrate into compliant, open three-dimensional (3D) forms. This approach not only enables efficient thermal impedance matching but also multiplies the heat flow through the harvester, thereby increasing the efficiencies for power conversion. Interconnected arrays of 3D thermoelectric coils built using microscale ribbons of monocrystalline silicon as the active material demonstrate these concepts. Quantitative measurements and simulations establish the basic operating principles and the key design features. The results suggest a scalable strategy for deploying hard thermoelectric thin-film materials in harvesters that can integrate effectively with soft materials systems, including those of the human body.

Morphable 3D mesostructures and microelectronic devices by multistable buckling mechanics.

Three-dimensional (3D) structures capable of reversible transformations in their geometrical layouts have important applications across a broad range of areas. Most morphable 3D systems rely on concepts inspired by origami/kirigami or techniques of 3D printing with responsive materials. The development of schemes that can simultaneously apply across a wide range of size scales and with classes of advanced materials found in state-of-the-art microsystem technologies remains challenging. Here, we introduce a set of concepts for morphable 3D mesostructures in diverse materials and fully formed planar devices spanning length scales from micrometres to millimetres. The approaches rely on elastomer platforms deformed in different time sequences to elastically alter the 3D geometries of supported mesostructures via nonlinear mechanical buckling. Over 20 examples have been experimentally and theoretically investigated, including mesostructures that can be reshaped between different geometries as well as those that can morph into three or more distinct states. An adaptive radiofrequency circuit and a concealable electromagnetic device provide examples of functionally reconfigurable microelectronic devices.

PCR-Free Colorimetric DNA Hybridization Detection Using a 3D DNA Nanostructured Reporter Probe.

A "sandwich-like" biosensor was developed on the basis of the magnetic bead platform for sensitive detection of breast cancer 1 (BRCA1) DNA. In the present study, a tetrahedron-structured reporter probe (TSRP) was designed, in which 3 vertices of the tetrahedron were labeled with digoxin (Dig), and the other one was labeled with a detection probe. TSRP here provided accurate enzyme loading and well-organized spatial arrangement for optimized signal amplification. The detection limit of this biosensor was as low as 10 fM, which is at least 4 orders of magnitude lower than that of the single DNA probe (100 pM), and the signal gain was 2 times higher than the analysis using three one-dimensional (1D) reporter probes. We could distinguish DNA sequences with only 1 base mismatch, and the performance of our TSRP biosensor was proven to be equally good in both PCR products and real fetal calf serum (FCS) sample as in buffer. We believe this work provided a novel avenue for the development of signal amplification strategies.

[Evaluation of Medical Instruments Cleaning Effect of Fluorescence Detection Technique].

OBJECTIVE: To compare the cleaning effect of automatic cleaning machine and manual cleaning on coupling type surgical instruments. METHODS: A total of 32 cleaned medical instruments were randomly sampled from medical institutions in Putuo District medical institutions disinfection supply center. Hygiena System SUREII ATP was used to monitor the ATP value, and the cleaning effect was evaluated. RESULTS: The surface ATP values of the medical instrument of manual cleaning were higher than that of the automatic cleaning machine. CONCLUSION: Coupling type surgical instruments has better cleaning effect of automatic cleaning machine before disinfection, the application is recommended.

The effect of recombinant sTGFß1RII and sIL13Rα2 receptor proteins on schistosomiasis japonica, hepatic fibrosis and signal transduction in a mouse model of schistosome disease.

This study was designed to investigate the effect of recombinant sTGFß1RII and sIL13Rα2 receptor proteins on schistosomiasis japonica, hepatic fibrosis and the expression of SMAD3 and STAT6. The proteins sTGFß1RII and sIL13Rα2 were expressed in Escherichiacoli, purified using affinity chromatography and characterized by Western blotting. Female BALB/C mice (48) were randomly divided into eight groups and infected with Schistosoma japonicum. Five weeks after infection, test groups were injected with the recombinant proteins at different doses. Eight weeks after infection, lung and hepatic tissue samples were obtained and stained with hematoxylin and eosin (HE) and Masson's trichrome. Immunohistochemical staining was used to detect the expression of SMAD3 and STAT6. The recombinant proteins sTGFß1RII and sIL13Rα2 were successfully expressed, purified, and characterized. The granuloma area, hepatic hydroxyproline (HYP) level and hepatic fibrosis of the protein therapeutic groups were significantly smaller than those of the positive control group (P<0.01). Treatment with sTGFß1RII was more effective when the protein was administered for 4weeks rather than 2 (P<0.01). Hepatic fibrosis in the groups using a low dose of protein sTGFß1 was lower that of the combination group (P<0.05). The expression level of STAT6 was significantly lower in groups treated with sIL13Rα2 than in groups not treated with the protein (P<0.01). The recombinant proteins TGFß1RII and sIL13Rα2 were able to decrease granuloma area and hepatic fibrosis in schistosomiasis japonica, and also reduced the expression of the signal transduction proteins SMAD3 and STAT6. The proteins were more effective when used in combination than when applied singly.

[The role of transforming growth factor beta1 R II and interleukin 13 Ralpha2 in schistosomiasis-induced hepatic fibrosis].

Schistosomiasis hepatic fibrosis results from excessive deposition of extracellular matrix components which are produced from the activated hepatic stellate cells in liver. Cytokine network disorder is the essential cause of the development of schistosomiasis liver fibrosis. Transforming growth factor beta1 (TGF-beta1) and interleukin 13 (IL-13) promote fibrosis through hepatic stellate cell membrane-specific receptor. This paper reviews the effects of TGF-beta1 type II (TGF-beta1 R II) receptor and IL-13 receptor alpha2 (IL-13 Ralpha2) on hepatic fibrosis.