4D label-free proteomics analysis of oxygen-induced retinopathy with or without anti-VEGF treatment.

Oxygen-induced retinopathy (OIR) animal model is widely used for retinopathy of prematurity (ROP) researches. The purpose of this study was to identify proteins and related pathways of OIR with or without anti-vascular endothelial growth factor (VEGF) treatment, for use as biomarkers in diagnosing and treating ROP. Nine samples were subjected to proteomic analysis. Retina specimens were collected from 3 OIR mice, 3 OIR mice with anti-VEGF treatment and 3 normal mice (control group). Liquid chromatography-tandem mass spectrometry analysis was performed using the 4D label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, InterPro (IPR) and protein interactions were analyzed. In total, 4585 unique proteins were identified as differentially expressed proteins (DEPs). Enrichment analysis of the GO and KEGG indicated functional clusters related to peptide biosynthetic and metabolic process, cellular macromolecule biosynthetic process and nucleic acid binding in OIR group. For anti-VEGF treatment group, DEPs were clustered in DNA replication, PI3K/Akt signaling pathway and Jak/STAT signaling pathway. Proteomic profiling is useful for the exploration of molecular mechanisms of OIR and mechanisms of anti-VEGF treatment. These findings may be useful for identification of novel biomarkers for ROP pathogenesis and treatment.

Semi-supervised correction model for turbulence-distorted images.

Significant progress has been made in addressing turbulence distortion in recent years, but persistent challenges remain. Firstly, existing methods heavily rely on fully supervised optimization strategies and synthetic datasets, posing difficulties in effectively utilizing unlabeled real data for training. Secondly, most approaches construct networks in a straightforward manner, overlooking the representation model of phase distortion and point spread function (PSF) in spatial and channel dimensions. This oversight restricts the potential for distortion correction. To address these challenges, this paper proposes a semi-supervised atmospheric turbulence correction method based on the mean-teacher framework. Our approach imposes constraints on the unlabeled data of student networks using pseudo-labels generated by teacher networks, thereby enhancing the generalization ability by leveraging information from unlabeled data. Furthermore, we introduce to use no-reference image quality assessment criterion to select the most reliable pseudo-label for each unlabeled sample by predicting physical parameters that indicating the level of degradation. Additionally, we propose to combine sliding window-based self-attention with channel attention to facilitate local-global context interaction. This design is inspired by the representation of phase distortion and PSF, which can be characterized by coefficients and basis functions corresponding to the channel-wise representation of convolutional neural network features. Moreover, the base functions exhibit spatial correlation, akin to Zenike and Airy disks. Experimental results show that the proposed method surpasses state-of-the-art models.

EEG-based assessment of temporal fine structure and envelope effect in mandarin syllable and tone perception.

In recent years, speech perception research has benefited from low-frequency rhythm entrainment tracking of the speech envelope. However, speech perception is still controversial regarding the role of speech envelope and temporal fine structure, especially in Mandarin. This study aimed to discuss the dependence of Mandarin syllables and tones perception on the speech envelope and the temporal fine structure. We recorded the electroencephalogram (EEG) of the subjects under three acoustic conditions using the sound chimerism analysis, including (i) the original speech, (ii) the speech envelope and the sinusoidal modulation, and (iii) the fine structure of time and the modulation of the non-speech (white noise) sound envelope. We found that syllable perception mainly depended on the speech envelope, while tone perception depended on the temporal fine structure. The delta bands were prominent, and the parietal and prefrontal lobes were the main activated brain areas, regardless of whether syllable or tone perception was involved. Finally, we decoded the spatiotemporal features of Mandarin perception from the microstate sequence. The spatiotemporal feature sequence of the EEG caused by speech material was found to be specific, suggesting a new perspective for the subsequent auditory brain-computer interface. These results provided a new scheme for the coding strategy of new hearing aids for native Mandarin speakers.

Investigating the Molecular Rearrangement of Polar Liquid Mixtures Using Terahertz Frequency Domain Reflection Spectroscopy.

A special data processing method for the terahertz frequency domain reflection spectroscopy system has been proposed to analyze the characteristics of a polar mixed liquid. This novel and practical measurement system is characterized by a simpler optical structure and a tunable output frequency range of 0.1-1 THz. By Hilbert transform, stationary wavelet transform, and time domain zero setting method, the reflection coefficient that has been eliminated by the noise and the Fabry-Pérot effect can be obtained by the self-reference calibration method. Then, the dielectric function of the ethanol/n-hexane and propanol/n-hexane mixtures with different mixture ratios can be extracted by this method. In addition, a significant deviation can be observed between the imaginary part of the measured dielectric function and the ideal calculated value. These results indicate that during the mixing process of polar and nonpolar liquids, the hydroxyl functional groups of alcohols significantly change the molecular arrangement pattern of the mixture. The arrangement pattern will result in the formation of the new permanent dipole moment. This study lays a solid foundation for future research on the microscopic mechanism of intermolecular interaction using terahertz frequency domain reflection spectroscopy.

Real-time diagnosis and Gleason grading of prostate core needle biopsies using nonlinear microscopy.

Rapid histologic assessment of fresh prostate biopsies may reduce patient anxiety, aid in biopsy sampling, and enable specimen triaging for molecular/genomic analyses and research that could benefit from fresh tissue analysis. Nonlinear microscopy (NLM) is a fluorescence microscopy technique that can produce high-resolution images of freshly excised tissue resembling formalin-fixed paraffin-embedded (FFPE) H&E. NLM enables evaluation of tissue up to ~100 µm below the surface, analogous to serial sectioning, but without requiring microtome sectioning. One hundred and seventy biopsies were collected from 63 patients who underwent in-bore MRI or MRI/ultrasound fusion biopsy procedures. Biopsies were stained in acridine orange and sulforhodamine 101, a nuclear and cytoplasmic/stromal fluorescent dye, for 45 s. Genitourinary pathologists evaluated the biopsies using NLM by translating the biopsies in real time to areas of interest and NLM images were recorded. After NLM evaluation, the biopsies were processed for standard FFPE H&E and similarities and differences between NLM and FFPE H&E were investigated. Accuracies of NLM diagnoses and Gleason scores were calculated using FFPE histology as the gold standard. Pathologists achieved a 92.4% sensitivity (85.0-96.9%, 95% confidence intervals) and 100.0% specificity (94.3-100.0%) for detecting carcinoma compared to FFPE histology. The agreement between the Grade Group determined by NLM versus FFPE histology had an unweighted Cohen's Kappa of 0.588. The average NLM evaluation time was 2.10 min per biopsy (3.08 min for the first 20 patients, decreasing to 1.54 min in subsequent patients). Further studies with larger patient populations, larger number of pathologists, and multiple institutions are warranted. NLM is a promising method for future rapid evaluation of prostate needle core biopsies.

INTERNAL LIMITING MEMBRANE PEELING DISTORTS THE RETINAL LAYERS AND INDUCES SCOTOMA FORMATION IN THE PERIFOVEAL TEMPORAL MACULA.

PURPOSE: To determine whether internal limiting membrane peeling damages retinal function in patients with an idiopathic macular hole. METHODS: Retrospective case series. Forty-five eyes of 45 idiopathic macular hole patients who underwent vitrectomy with internal limiting membrane peeling with a minimum follow-up of 6 months. Each patient received a complete ophthalmological examination. The eyes were examined by microperimetry MP-3 in the central 20° visual field and optical coherence tomography angiography in the central 6 × 6 mm area. RESULTS: Six months after the surgery, macular hole closed in each patient. Retinal sensitivity decreased significantly in the perifoveal temporal ETDRS sector (from 24.97 ± 2.67-19.98 ± 5.68 dB, P = 0.001) but not in the other sectors. Six patients (13%) developed 24 scotomas, 62.5% presented in the perifoveal temporal sector. Anatomically, bumps in the outer nuclear layer were discovered concurrent with inner retinal dimples on B-scan images, predominantly (76.8%) in the perifoveal temporal sector, which have not been previously reported. The incidence of outer nuclear layer bumps was significantly higher in patients with scotomas than in those without (83% vs. 18%, P = 0.014). CONCLUSION: Internal limiting membrane peeling induced functional changes specifically in the perifoveal temporal macula. Distortion in the retinal layers is proposed to underly scotomas pathogenesis.

Growth, Nutrient Retention, Waste Output, and Antioxidant Capacity of Juvenile Triangular Bream (Megalobrama terminalis) in Response to Dietary Selenium Yeast Concentration.

An 8-week feeding trial was conducted to investigate the effects of different dietary selenium yeast levels on growth, nutrient retention, waste output, and antioxidant capacity of juvenile triangular bream (Megalobrama terminalis). Five isonitrogenous (320 g/kg crude protein) and isolipidic (65 g/kg crude lipid) diets were formulated, with supplementation of graded levels of selenium yeast at 0 (diet Se0), 1 (diet Se1), 3 (diet Se3), 9 (diet Se9), and 12 g/kg (diet Se12). No significant differences were found in initial body weight, condition factor, visceral somatic index, hepatosomatic index, and whole body contents of crude protein, ash, and phosphorus among fish fed different test diet. The highest final body weight and weight gain rate were found in fish fed diet Se3. The specific growth rate (SGR) is closely related to dietary selenium (Se) concentrations with a relationship described as SGR = -0.0043 Se2 + 0.1062 Se + 2.661. Higher feed conversion ratio was found, while lower retention efficiencies of nitrogen and phosphorus were found in fish fed diets Se1, Se3, and Se9 than in fish fed diet Se12. Contents of selenium in whole body, vertebra, and dorsal muscle increased with dietary supplementation of selenium yeast increased from 1 mg/kg to 9 mg/kg. Lower nitrogen and phosphorous waste was found in fish fed diets Se0, Se1, Se3, and Se9 than in fish fed diet Se12. Fish fed diet Se3 exhibited the highest activities of superoxide dismutase, glutathione peroxidase, and lysozyme while the lowest malonaldehyde content in both the liver and kidney. Our results showed that the optimal dietary selenium requirement for triangular bream should be 12.34 mg/kg based on the nonlinear regression on SGR, and fish fed diet Se3 in which selenium concentration (8.24 mg/kg) was close to the optimal requirement displayed the best growth performance, feed nutrient utilization, and antioxidant capacity.

Optical vortex switch based on multiplexed volume gratings with high diffraction efficiency.

Systems of controllable orbital angular momentum (OAM) require more compact, higher conversion efficiency and more tolerable wavelength or polarization. We introduce an optical vortex switch based on a multiplexed volume grating (MVG). The MVG recorded in a piece of photo-thermo-refractive (PTR) glass exhibits high diffraction efficiency (DE, also known as conversion efficiency in transporting), sensitive angular selectivity, and polarization-insensitivity. The effects of the incident divergence angle and polarization on the DE and the far-field diffraction profiles are demonstrated and investigated. It turns out that the divergence angle of the probe beam can greatly affect the DE. The fluctuation of the DE caused by polarization variation is less than 1.59%. This switch can be potentially applied in vortex tweezers, optical communication, and high power systems.

The determination of antibacterial mode for cationic lipopeptides brevibacillins against Salmonella typhimurium by quantum chemistry calculation.

Brevibacillins are broad-spectrum cationic antimicrobial lipopeptides produced by Brevibacillus laterosporus fmb70 CGMCC 18426. The antibacterial mode of brevibacillins against Salmonella typhimurium CICC 21493 was investigated by quantum chemistry calculation in this study. The addition of LPS, Mg2+, and Ca2+ partially reduced the antimicrobial activity of brevibacillin and brevibacillin V against S. typhimurium, which indicated that the two cationic lipopeptides could bind to LPS and displaced the divalent cations on the LPS network. Release of LPS from S. typhimurium by brevibacillin and brevibacillin V resulted in destroying the dense LPS network and increasing the permeability of the outer membrane. Quantum chemistry calculation analysis revealed that Lys7 is the most critical amino acid residue to destroy the outer membrane. The total average N-H charge difference of the three protonated amino groups (Orn3-NH3, Lys7-NH3, and Lys10-NH3) determined the ability of brevibacillin V to bind LPS stronger than brevibacillin. Calcein complete leakage from liposomes and release of DiSC3-5 from the cytoplasmic membrane (CM) indicated that brevibacillin and brevibacillin V may destroy the CM. Brevibacillin and brevibacillin V exhibited their antimicrobial activities through membrane damages, where the OM permeability with high concentration of 64-256 µg/mL and membrane damage of CM with a low concentration of 4 µg/mL. Our finding might be helpful to understand the broad-spectrum antimicrobial mechanism of cationic lipopeptide and to design the novel antimicrobial peptide. KEY POINTS: • Brevibacillin V had stronger affinity for LPS than brevibacillin. • The N-H charge difference was the key of the difference in the affinity to LPS. • Brevibacillins inhibited Salmonella by displacing the divalent cations on the LPS.

Salvianolic Acid A Protects H9C2 Cardiomyocytes from Doxorubicin-Induced Damage by Inhibiting NFKB1 Expression Thereby Downregulating Long-Noncoding RNA (lncRNA) Plasmacytoma Variant Translocation 1 (PVT1).

BACKGROUND A cardioprotective effect of salvianolic acid A (SalA) has been described, but it is unknown whether SalA can protect cardiomyocytes against doxorubicin (Dox)-induced cardiotoxicity. This study aimed to investigate whether SalA could inhibit Dox-induced apoptosis in H9C2 cells and to uncover the potential mechanism. MATERIAL AND METHODS H9C2 cardiomyocytes exposed to Dox were treated with SalA or not, and then cell viability, apoptosis, and the expression of nuclear factor-kappaB (NF-kappaB) signaling were detected by Cell Counting Kit-8, TUNEL staining, and western blot assays, respectively. Nuclear factor kappa B subunit 1 (NFKB1) was overexpressed in H9C2 cells, and then alterations in cell viability and apoptosis in H9C2 cells co-treated with Dox and SalA were investigated. RESULTS SalA (2, 10, and 50 µM) had no effect on H9C2 cell viability, while Dox reduced cell viability in a concentration-dependent manner. In addition, SalA rescued Dox-decreased cell viability. Dox also triggered apoptosis as evidenced by an increased ratio of TUNEL-positive cells, enhanced expression of pro-apoptotic proteins, and reduced expression of anti-apoptotic protein BCL-2, which were all partially blocked by SalA co-treatment. The proteins involved in NF-kappaB signaling including IkappaBalpha, IKKalpha, IKKß, and p65 were activated by Dox but inactivated by SalA co-treatment. Moreover, Dox increased NFKB1 mRNA and nuclear expression, which was blocked by SalA. NFKB1 could bind to plasmacytoma variant translocation 1 (PVT1) and upregulate PVT1 expression. Mechanistically, the overexpression of NFKB1 blocked the inhibitory effect of SalA on Dox-induced cell viability impairment and apoptosis. CONCLUSIONS We demonstrated that SalA may exert a protective effect against Dox-induced H9C2 injury and apoptosis via inhibition of NFKB1 expression, thereby downregulating lncRNA PVT1.

Gene networks and toxicity/detoxification pathways in juvenile largemouth bass (Micropterus salmoides) liver induced by acute lead stress.

Lead (Pb) is a nonessential heavy metal that can be bioconcentrated to highly toxic levels in the environment. To understand the genes and toxicity/detoxification pathways of juvenile largemouth bass, liver transcriptomes were investigated in this fish after acute 96 h Pb exposure (Pb nitrate 0, 17.8, or 100 mg/L). Acute Pb exposure induced an immune response and apoptosis pathway activation in the liver. A number of transcripts related to complement and coagulation cascades were significantly increased. Up- and downregulated genes were significantly enriched in numerous pathways, including the natural killer cell-mediated cytotoxicity pathway, the Jak-STAT and P53 signaling pathways, cancer and apoptosis. These genes included Bid，Bcl-2, JNK, and PI3K (17.8 mg/L) and PI3K, AKT, PPARδ, RAS, MMPs, c-Jun p53, and PD-L1 (100 mg/L). Comprehensive analysis of liver transcriptomic data revealed numerous pathways associated with the immune system and carcinogenesis, especially pathways related to apoptosis and systemic lupus erythematosus.

Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies.

Intraoperative evaluation of specimens during radical prostatectomy using frozen sections can be time and labor intensive. Nonlinear microscopy (NLM) is a fluorescence microscopy technique that can rapidly generate images that closely resemble H&E histology in freshly excised tissue, without requiring freezing or microtome sectioning. Specimens are stained with nuclear and cytoplasmic/stromal fluorophores, and NLM evaluation can begin within 3 min of grossing. Fluorescence signals can be displayed using an H&E color scale, facilitating pathologist interpretation. This study evaluates the accuracy of prostate cancer detection in a blinded reading of NLM images compared with the gold standard of formalin-fixed, paraffin-embedded H&E histology. A total of 122 freshly excised prostate specimens were obtained from 40 patients undergoing radical prostatectomy. The prostates were grossed, dissected into specimens of ~10 × 10 mm with 1-4 mm thickness, stained for 2 min for nuclear and cytoplasmic/stromal contrast, and then rinsed with saline for 30 s. NLM images were acquired and multiple images were stitched together to generate large field of view, centimeter-scale digital images suitable for reading. Specimens were then processed for standard paraffin H&E. The study protocol consisted of training, pretesting, and blinded reading phases. After a washout period, pathologists read corresponding paraffin H&E slides. Three pathologists achieved a 95% or greater sensitivity with 100% specificity for detecting cancer on NLM compared with paraffin H&E. Pooled sensitivity and specificity was 97.3% (93.7-99.1%; 95% confidence interval) and 100.0% (97.0-100.0%), respectively. Interobserver agreement for NLM reading had a Fleiss κ = 0.95. The high cancer detection accuracy and rapid specimen preparation suggest that NLM may be useful for intraoperative evaluation in radical prostatectomy.

A highly potent maytansinoid analogue and its use as a cytotoxic therapeutic agent in gold nanoparticles for the treatment of hepatocellular carcinoma.

Gold nanoparticles are promising drug delivery agents with the potential to deliver chemotherapeutic agents to tumour sites. The highly cytotoxic maytansinoid tubulin inhibitor DM1 has been attached to gold nanoparticles and shows tumour growth inhibition in mouse models of hepatocellular carcinoma. Attempting to improve the stability of the gold-cytotoxin bond led to the design and synthesis of novel maytansinoids with improved potency in cell viability assays and improved in vivo tolerability compared to the DM1 analogues. These novel maytansines may also have applications in other methods of drug delivery, for example as the cytotoxic component of antibody drug conjugates.

Exploring the Potential of Hydrophilic Matrix Combined with Insoluble Film Coating: Preparation and Evaluation of Ambroxol Hydrochloride Extended Release Tablets.

To explore the potential utility of combination of hydrophilic matrix with membrane-controlled technology, the present study prepared tablets of a water-soluble model drug (ambroxol hydrochloride), through process of direct compression and spray coating. Single-factor experiments were accomplished to optimize the formulation. In vivo pharmacokinetics was then performed to evaluate the necessity and feasibility of further development of this simple process and low-cost approach. Various release rates could be easily obtained by adjusting the viscosity and amount of hypromellose, pore-former ratios in coating dispersions and coating weight gains. Dissolution profiles of coated tablets displayed initial delay, followed by near zero-order kinetics. The pharmacokinetic study of different formulations showed that lag time became longer as the permeability of coating membrane decreased, which was consistent with the in vitro drug release trend. Besides, in vitro/in vivo correlation study indicated that coated tablets exhibited a good correlation between in vitro release and in vivo absorption. The results, therefore, demonstrated that barrier-membrane-coated matrix formulations were extremely promising for further application in industrialization and commercialization.

Analysis of risk factors for progressive fibrovascular proliferation in proliferative diabetic retinopathy.

PURPOSE: To investigate the risk factors associated with progressive fibrovascular proliferation (FVP) in proliferative diabetic retinopathy (PDR). METHODS: We retrospectively reviewed the clinical data of patients who underwent pars plana vitrectomy for PDR between August 2017 and October 2019 at our department of ophthalmology. The FVP was divided into five grades based on the coverage area of proliferative membrane. Then we compared the patients with different severities of FVP to analyze the risk factors for higher grade of FVP in PDR. RESULTS: Univariate analysis showed that positive urinary protein (p = 0.007), higher levels of serum blood urea nitrogen (BUN) (p < 0.001) and serum creatinine (p < 0.001), more severe stage of estimated glomerular filtration rate (p < 0.001), age < 45 years (p = 0.005), longer duration of diabetic retinopathy (p = 0.007), history of hypertension (p = 0.034) and smoking (p = 0.008) were related to FVP grade ≥ 3. Multivariate analysis showed that the level of BUN, age < 45 years and smoking were independent risk factors for FVP grade ≥ 3 in PDR patients. CONCLUSION: This study demonstrated that BUN (odds ratio [OR] = 1.318, 95% confidence interval [CI] = 1.150-1.511, p < 0.001), age ≤ 45 years (OR = 3.774, 95% CI = 1.762-8.082, p = 0.001) and smoking (OR = 2.111, 95% CI = 1.040-4.288, p = 0.039) were independent risk factors for progressive FVP in PDR among northeastern Chinese patients.

Comparing histologic evaluation of prostate tissue using nonlinear microscopy and paraffin H&E: a pilot study.

Rapid histological assessment of large areas of prostate tissue is required for many intraoperative consultation scenarios such as margin evaluation. Nonlinear microscopy (NLM) enables imaging of large (whole mount) specimens without freezing or cryotoming. This study demonstrates rapid histological imaging of unsectioned prostate cancer surgical specimens using nonlinear microscopy and compares features of prostate pathology to standard paraffin embedded H&E histology. Fresh or formalin fixed specimens were stained in 2.5 min with fluorescent nuclear and stromal dyes. Nonlinear microscopy images of unsectioned tissues were generated by nonlinear (two-photon) excitation of the fluorophores, where fluorescence is only emitted from tissue at the microscope focus, avoiding the need for physical sectioning. The images were displayed in real time using a color scale similar to H&E, then tissues were processed for standard paraffin embedded H&E histology. Seventy nonlinear microscopy and corresponding paraffin H&E images of fresh and fixed prostate specimens (15 cancer, 55 benign) from 24 patients were read by genitourinary pathologists to assess if nonlinear microscopy could achieve an equivalent evaluation to paraffin embedded H&E histology. Differences between nonlinear microscopy images and paraffin H&E slides, including cytoplasmic color and stromal density, were observed, however nonlinear microscopy images could be interpreted with minimal training. Nonlinear microscopy enabled visualization of benign, atrophic and hyperplastic glands and stroma, ejaculatory ducts, vasculature and inflammatory changes. Nonlinear microscopy enabled identification of typical and variants of adenocarcinoma, as well as Gleason patterns. Perineural invasion and extraprostatic extension could also be assessed. Nonlinear microscopy images closely resemble paraffin H&E slides and enable rapid assessment of normal prostate architecture, benign conditions, and carcinoma in freshly excised and fixed specimens. Nonlinear microscopy can image large regions of tissue, equivalent to multiple frozen section tissue blocks, within minutes because cryotoming/microtoming are not required, making it a promising technique for intraoperative consultation.

Prediction accuracy of intraocular lens power calculation methods after laser refractive surgery.

BACKGROUND: This study aimed to evaluate the prediction accuracy of postoperative refractions using partial coherence interferometry (IOL-Master) and applanation ultrasound (AL-3000) assisted with corneal topography (TMS-4) in eyes that had undergone myopic laser-assisted in situ keratomileusis (LASIK). METHODS: Haigis-L formula, Koch-Maloney method using Haigis formula, Shammas clinically derived K-value (simulated keratometric value) correction (Shammas c.d.) using Haigis formula, and Shammas post-LASIK (Shammas-PL) formula were used in eyes with myopic LASIK. Constants were derived from the optimized constants in 133 virgin eyes. Refractive outcomes were determined by streak retinoscopy and subjective manifest refraction. Methods and formulas were evaluated by mean error (ME), standard deviation (SD), range of error, mean absolute error (MAE), median absolute error, 95% confidence interval of MAE, and percentage of eyes within ±0.5 diopter (D), ±1.0 D, and ±1.5 D of prediction. RESULTS: SDs of the Haigis-L, Koch-Maloney method using the Haigis formula, Shammas c.d. using the Haigis formula, and the Shammas-PL formula using IOL-Master were 0.721, 0.695, 0.695, and 0.698; and those using AL-3000 assisted with TMS-4 were 0.782, 0.741, 0.743, and 0.778, respectively. CONCLUSIONS: No-history methods that corrected corneal power with measurements using IOL-Master were promising in myopic post-LASIK eyes, but still a gap in prediction accuracy exists between virgin eyes and post-LASIK eyes.

Effect of blood glucose level on acute stress response of grass carp Ctenopharyngodon idella.

Stress has a considerable impact on welfare and productivity of fish, and blood glucose level of fish may be a factor modulating stress response. This study evaluated the effect of blood glucose level and handling on acute stress response of grass carp Ctenopharyngodon idella. Fish were intraperitoneally injected with glucose at 0, 0.2, 0.5, and 1.0 mg g-1 body mass (BM) and then were exposed to handling for 5 min. Glucose injection resulted in increase of plasma glucose level and liver glycogen content and decrease of plasma lactate level. Handling resulted in increase of plasma levels of cortisol, glucose, and lactate and plasma lactic dehydrogenase (LDH) activity and decrease of liver glycogen content. At 1 h post-stress, the plasma cortisol level was lower in the stressed fish injected with glucose at 0.5 mg g-1 BM than the stressed fish injected with glucose at 0, 0.2, and 1.0 mg g-1 BM. No significant differences were found in the activities of phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate kinase (PK) in the liver between the stressed and unstressed fish, regardless of the dose of glucose injection. At 1 h post-stress, the liver glucose-6-phosphatase (G6Pase) activity was higher in the fish without glucose injection than in the fish injected with glucose. This study reveals that blood glucose level can affect stress response of grass carp by modulating cortisol release and glucose homeostasis through glycogen metabolism and gluconeogenesis in the liver.

Rapidly dissolvable microneedle patches for transdermal delivery of exenatide.

PURPOSE: To assess the feasibility of transdermal delivery of exenatide (EXT) using low-molecular-weight sodium hyaluronate (HA) dissolving microneedles (MNs) patches for type 2 diabetes mellitus therapy. METHODS: Micromold casting method was used to fabricate EXT-loaded dissolving MNs. The characteristics of prepared MNs including mechanical strength, in vitro/in vivo insertion capacity, dissolution profile and storage stability were then investigated. Finally, the in vivo pharmacokinetics and hypoglycemic effects were compared with traditional subcutaneous (SC) injection. RESULTS: EXT-loaded dissolving MNs made of HA possessed sufficient mechanical strength and the strength could be weakened as the water content increases. The EXT preserved its pharmacological activity during fabrication and one-month storage. With the aid of spring-operated applicator, dissolving MNs could be readily penetrated into the skin in vitro/in vivo, and then rapidly dissolved to release encapsulated drug within 2 min. Additionally, transepidermal water loss (TEWL) determinations showed that skin's barrier properties disrupted by MNs recovered within 10-12 h. Transdermal pharmacokinetics and antidiabetic effects studies demonstrated that fabricated EXT MNs induced comparable efficacy to SC injection. CONCLUSIONS: Our rapidly dissolving MNs patch appears to an excellent, painless alternative to conventional SC injection of EXT, and this minimally invasive device might also be suitable for other biotherapeutics.

Benchtop fine needle aspirations: An untapped source of cytologic educational material.

Fine needle aspirations (FNAs) are a valuable tool for the diagnosis of a wide variety of lesions. However, obtaining proficiency in performing FNAs and finding simulated scenarios where one can practice specimen adequacy and slide smearing can all be challenging. Benchtop FNAs of fresh surgical specimens offer a novel training opportunity that addresses these needs. In this study, we describe the feasibility and practicality of benchtop FNAs of fresh surgical specimens as a training tool. We performed benchtop FNAs on multiple specimen types, although most were partial and radical nephrectomies. We documented this approach to cytology training and have provided examples of slides that were generated, along with the surgical pathology correlate. Our results suggest that benchtop FNAs of fresh surgical specimens can be a valuable training tool in the arsenal of today's cytopathologist. This technique offers several advantages over traditional training methods, including the ability to generate high-quality cytology slides, provide cyto-histo correlation, and practice almost immediate gross-microscopic correlation. However, there are also some disadvantages to this approach, including the need for immediate access to fresh surgical specimens and the potential for artifacts to be introduced. Overall, we believe that benchtop FNAs of fresh surgical specimens offer a promising new training tool that can maximize training opportunities, especially in institutions where the FNA volume is low.