Defining multistep cell fate decision pathways during pancreatic development at single-cell resolution.

The generation of terminally differentiated cell lineages during organogenesis requires multiple, coordinated cell fate choice steps. However, this process has not been clearly delineated, especially in complex solid organs such as the pancreas. Here, we performed single-cell RNA-sequencing in pancreatic cells sorted from multiple genetically modified reporter mouse strains at embryonic stages E9.5-E17.5. We deciphered the developmental trajectories and regulatory strategies of the exocrine and endocrine pancreatic lineages as well as intermediate progenitor populations along the developmental pathways. Notably, we discovered previously undefined programs representing the earliest events in islet α- and ß-cell lineage allocation as well as the developmental pathway of the "first wave" of α-cell generation. Furthermore, we demonstrated that repressing ERK pathway activity is essential for inducing both α- and ß-lineage differentiation. This study provides key insights into the regulatory mechanisms underlying cell fate choice and stepwise cell fate commitment and can be used as a resource to guide the induction of functional islet lineage cells from stem cells in vitro.

Understanding generation and regeneration of pancreatic ß cells from a single-cell perspective.

Understanding the mechanisms that underlie the generation and regeneration of ß cells is crucial for developing treatments for diabetes. However, traditional research methods, which are based on populations of cells, have limitations for defining the precise processes of ß-cell differentiation and trans-differentiation, and the associated regulatory mechanisms. The recent development of single-cell technologies has enabled re-examination of these processes at a single-cell resolution to uncover intermediate cell states, cellular heterogeneity and molecular trajectories of cell fate specification. Here, we review recent advances in understanding ß-cell generation and regeneration, in vivo and in vitro, from single-cell technologies, which could provide insights for optimization of diabetes therapy strategies.

Effects of hypoxia on the gill morphological structure, apoptosis and hypoxia-related gene expression in blunt snout bream (Megalobrama amblycephala).

The blunt snout bream (Megalobrama amblycephala) is a typical hypoxia-sensitive fish, and hypoxia stress leads to reduced vitality and yield during aquaculture. To explore the specific adaptation mechanism under hypoxia, the blunt snout bream was treated with hypoxia (DO = 2.0 ± 0.1 mg/L) for 24 h, followed by 3 h of recovery. Our results depicted that the gill filament structure of blunt snout bream changed after hypoxia. During hypoxia for 24 h, the gill filament structure was altered, including a more than 80% expansion of the lamellar respiratory surface area and a proportionate apoptosis decrease in interlamellar cell mass (ILCM) volume. Thus, the water-blood diffusion distance was shortened to less than 46%. During hypoxia for 24 h, the activity of ROS in gill tissue increased significantly (p < 0.05), while the mitochondrial membrane potential decreased significantly (p < 0.05). During hypoxia, mRNA expression level of anti-apoptotic gene Bcl-2 in the gills of blunt snout bream decreased significantly (p < 0.05), while the expression of pro-apoptotic gene Bax mRNA increased significantly (p < 0.05). Thus, the ratio of Bax/Bcl-2 mRNA increased in the gills of blunt snout bream to promote the activity of Caspase-3. Together, our results indicated hypoxia-induced apoptosis in the gills of blunt snout bream through the mitochondrial pathway. In addition, a decreased expression of Phd1 and an increased expression of Hif-1α in gills under hypoxia stress indicates that blunt snout bream may cope with hypoxia-induced apoptosis by enhancing the HIF pathway. These results provide new insights into fish's adaptation strategies and mechanisms of hypoxia.

Dynamics of chromatin marks and the role of JMJD3 during pancreatic endocrine cell fate commitment.

Pancreatic endocrine lineages are derived from pancreatic progenitors that undergo a cell fate transition requiring a switch from low to high Ngn3 expression. However, the underlying chromatin regulatory mechanisms are unclear. Here, we performed epigenomic analysis of gene regulatory loci featuring histone marks in cells with low or high level of Ngn3 expression. In combination with transcriptomic analysis, we discovered that in Ngn3-high cells, the removal of H3K27me3 was associated with the activation of key transcription factors and the establishment of primed and active enhancers. Deletion of Jmjd3, a histone demethylase for H3K27me3, at the pancreatic progenitor stage impaired the efficiency of endocrine cell fate transition and thereafter islet formation. Curiously, single-cell RNA-seq revealed that the transcriptome and developmental pathway of Ngn3-high cells were not affected by the deletion of Jmjd3 Our study indicates sequential chromatin events and identifies a crucial role for Jmjd3 in regulating the efficiency of the transition from Ngn3-low to Ngn3-high cells.

C-C chemokine receptor type 1 mediates osteopontin-promoted metastasis in hepatocellular carcinoma.

In the hepatocellular carcinoma (HCC) microenvironment, chemokine receptors play a critical role in tumorigenesis and metastasis. Our previous studies have found that osteopontin (OPN) is a promoter for HCC metastasis. However, the role of chemokine receptors in OPN-induced HCC metastasis remains unclear. In this study, we demonstrate that OPN is dramatically elevated in HCC tissues with metastasis and that high expression of OPN correlates with poorer overall survival and higher recurrence rate. OPN upregulates chemokine receptor expression, migration, invasion and pulmonary metastasis in HCC. We find that C-C chemokine receptor type 1 (CCR1) and C-X-C chemokine receptor type 6 (CXCR6) are the most upregulated chemokine receptors induced by OPN. CCR1 knockdown results in reduction of migration, invasion and pulmonary metastasis induced by OPN in vitro and in vivo, whereas CXCR6 knockdown does not reverse OPN-promoted migration and invasion. Moreover, OPN upregulates the expression of CCR1 through activating phosphoinositide 3-kinase (PI3K)/AKT and hypoxia-inducible factor 1α (HIF-1α) in HCC cells. Furthermore, blockade of OPN-CCR1 axis with CCR1 antagonist significantly restrains the promoting effects of OPN on HCC progression and metastasis. In human HCC tissues, OPN expression shows significantly positive correlation with CCR1 expression, and the patients with high levels of both OPN and CCR1 have the most dismal prognosis. Collectively, our results indicate that the OPN-CCR1 axis in HCC is important for accelerating tumor metastasis and that CCR1 is a potential therapeutic target for controlling metastasis in HCC patients with high OPN.

Glucagon is the key factor in the development of diabetes.

Glucagon plays important roles in normal glucose homeostasis and in metabolic abnormalities, particularly diabetes. Glucagon excess, rather than insulin deficiency, is essential for the development of diabetes for several reasons. Glucagon increases hepatic glucose and ketone production, the catabolic features of insulin deficiency. Hyperglucagonaemia is present in every form of diabetes. Beta cell destruction in glucagon receptor null mice does not cause diabetes unless mice are administered adenovirus encoding the glucagon receptor. In rodent studies the glucagon suppressors leptin and glucagon receptor antibody suppressed all catabolic manifestations of diabetes during insulin deficiency. Insulin prevents hyperglycaemia; however, insulin monotherapy cannot cure diabetes such that non-diabetic glucose homeostasis is achieved. Glucose-responsive beta cells normally regulate alpha cells, and diminished insulin action on alpha cells will favour hypersecretion of glucagon by the alpha cells, thus altering the insulin:glucagon ratio. Treating diabetes by suppression of glucagon, with leptin or antibody against the glucagon receptor, normalised glucose level (without glycaemic volatility) and HbA1c. Glucagon suppression also improved insulin sensitivity and glucose tolerance. If these results can be translated to humans, suppression of glucagon action will represent a step forward in the treatment of diabetes. This review summarises a presentation given at the 'Novel data on glucagon' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Mona Abraham and Tony Lam, DOI: 10.1007/s00125-016-3950-3 , and by Russell Miller and Morris Birnbaum, DOI: 10.1007/s00125-016-3955-y ) and an overview by the Session Chair, Isabel Valverde (DOI: 10.1007/s00125-016-3946-z ).

Effect of tiotropium on neural respiratory drive during exercise in severe COPD.

BACKGROUND: Studies have shown that tiotropium once daily reduces lung hyperinflation and dyspnea during exercise and improves exercise tolerance in patients with COPD. Mechanisms underlying the effects of the muscarinic receptor antagonist tiotropium on COPD have not been fully understood. OBJECTIVE: In this study, we investigated whether improvement in neural respiratory drive is responsible for reducing dyspnea during exercise and improving exercise tolerance in COPD. METHODS: Twenty subjects with severe COPD were randomized into two groups: no treatment (Control, n = 10, 63.6 ± 4.6 years, FEV1 29.6 ± 13.3%pred) or inhaled tiotropium 18 µg once daily for 1 month (n = 10, 66.5 ± 5.4 years, FEV1 33.0 ± 11.1%pred). All subjects were allowed to continue their daily medications other than anti-cholinergics during the study. Constant cycle exercise with 75% of maximal workload and spirometry were performed before and 1 month after treatment. Diaphragmatic EMG (EMGdi) and respiratory pressures were recorded with multifunctional esophageal catheter. Efficiency of neural respiratory drive, defined as the ratio of minute ventilation (VE) and diaphragmatic EMG (VE/EMGdi%max), was calculated. Modified British Medical Research Council Dyspnea Scale (mMRC) was used for the evaluation of dyspnea before and after treatment. RESULTS: There was no significant difference in spirometry before and after treatment in both groups. Diaphragmatic EMG decreased significantly at rest (28.1 ± 10.9% vs. 22.6 ± 10.7%, P < 0.05) and mean efficiency of neural respiratory drive at the later stage of exercise increased (39.8 ± 2.9 vs. 45.2 ± 3.9, P < 0.01) after 1-month treatment with tiotropium. There were no remarkable changes in resting EMGdi and mean efficiency of neural respiratory drive post-treatment in control group. The score of mMRC decreased significantly (2.5 ± 0.5 vs. 1.9 ± 0.7, P < 0.05) after 1-month treatment with tiotropium, but without significantly difference in control group. CONCLUSION: Tiotropium significantly reduces neural respiratory drive at rest and improves the efficiency of neural respiratory drive during exercise, which might account for the improvement in exercise tolerance in COPD.

Response--dose ratio is a surrogate of cumulative provocative dosage for bronchial provocation tests in asthma.

BACKGROUND: Response-dose ratio (RDR) and cumulative provocative dosage (PD) are useful indices reflecting airway responsiveness in asthma. OBJECTIVES: To compare the diagnostic value of RDR and PD, by conducting leukotriene D4 (LTD4-BPT) and methacholine bronchial provocation test (MCh-BPT), in different asthma control levels. METHODS: Healthy subjects and asthmatic patients underwent LTD4-BPT and MCh-BPT, at 2-14-day interval. This entailed assessment of the distribution characteristics, correlation, and diagnostic value of PD inducing 20% fall in forced expiratory volume in one second (PD20FEV1) and the RDR, defined as FEV1 fall (%) at the final step divided by the corresponding provocative dosage. RESULTS: Twenty uncontrolled, 22 partly controlled, 20 controlled asthmatics, and 21 healthy subjects were enrolled. Log10RDR was positively correlated with log10PD20FEV1 in both BPTs (all P < 0.05). Poorer asthma control was associated with significantly lower PD20FEV1 and higher RDR (both P < 0.05). The differences in PD20FEV1 and RDR between partly controlled and controlled asthma were unremarkable (both P > 0.05). Compared with log10PD20FEV1, the log10RDR yielded similar diagnostic values in both BPTs. A lower percentile of RDR (≤ 25th percentile) was associated with higher baseline FEV1 (P < 0.05) and an increased proportion of well-controlled asthmatic patients. The combination of RDR and PD20FEV1 led to an increased diagnostic value compared with either parameter alone. CONCLUSIONS: RDR is a surrogate of PD20FEV1 for BPTs in asthma. This finding was not modified by different asthma control levels or the types of bronchoprovocants.

The selfie sign in the diagnosis of functional tremor.

Functional tremor (FT) is the most common phenotype of functional movement disorders (FMD). Its diagnosis can often be challenging. While positive signs such as tremor variability, distractibility, and entrainment support a diagnosis of FT, these diagnostic clues may not always be present and can be challenging to assess. In this case series, we identify another examination technique which could be of value when assessing FT. In our Movement Disorders clinic, charts were retrospectively reviewed for relevant clinical information. Video examinations were conducted. Obtained videos were either synchronous, via the use of screen recording software during telehealth visits or asynchronous, from self-recorded home videos. In both settings, patients were instructed to self-record their tremor using their phone cameras. Three patients with FT or comorbid FT were identified as demonstrating a unique examination sign. Videos showed an improvement or suppression of the tremor when the phone was held by the affected hand. When compared to a patient with tremor-dominant Parkinson's disease serving as a control, this "selfie sign" was not observed. These observations are preliminary and larger studies are needed to confirm the usefulness of the selfie sign in diagnosing FT. Patient-recorded videos of their tremor can be a convenient and practical way of evaluating suspected FT, especially when paroxysmal or variable symptoms limit the usefulness of classic signs often assessed in the clinic.

Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling. AIM: To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved. METHODS: Human vaginal wall collagen content was assessed by Masson's trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed via RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined via functional experiments in vitro. RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules. RESULTS: In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 µg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production in vitro. High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression. CONCLUSION: HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro. Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.

Introducing Virtual Shared Medical Appointments as a Novel Treatment Platform for Functional Movement Disorders.

The landscape of medical care has rapidly evolved with technological advancements, particularly through the widespread adoption of virtual appointments catalyzed by the COVID-19 pandemic. This shift has transcended geographical barriers, enhancing access for underserved populations and those with disabilities to specialized healthcare providers. A notable development stemming from this trend is the emergence of virtual shared medical appointments (VSMAs), which integrate group-based education with telemedicine technology. While VSMAs have demonstrated efficacy in conditions such as obesity, diabetes, and neurological disorders, their effectiveness in managing Functional Movement Disorders (FMD) is currently under investigation. FMDs pose unique challenges in diagnosis and acceptance, with high rates of misdiagnosis and treatment delays. VSMAs offer a promising solution by providing educational modules and fostering peer support among patients with similar diagnoses. At the Cleveland Clinic Center for Neurological Restoration, VSMAs have been embraced to enhance care standards for FMD patients. The program facilitates educational sessions and follow-up meetings to improve treatment adherence and psychological well-being. Early outcomes indicate increased patient acceptance and engagement, with significant program growth observed. Ongoing research aims to evaluate stakeholder perspectives and refine session content to further reduce stigma and the healthcare burden associated with FMDs.

[Single-breath and rebreathing methods for measurement of pulmonary diffusing function: a comparative study].

OBJECTIVE: To compare the difference of pulmonary diffusing capacity measured by single-breath (SB) and re-breathing (RB) in normal subjects, patients with interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). METHODS: We enrolled a cohort of subjects from the Guangzhou Institute of Respiratory Disease between September 2011 and February 2012: control group 29 (male 9, female 20, 42-74 y), ILD group 32 (male 15, female 17, 41-72 y), COPD group 32 (male 28, female 4, 40-75 y). All subjects underwent pulmonary diffusing capacity test using SB or RB method according to random figures order list. Diffusing capacity of carbon monoxide per predicted measured by SB method (SB-DLCO%pred) of the normal group was used as the standard to adjust the diffusing capacity of carbon monoxide per predicted measured by RB method (RB-DLCO%pred) and diffusing capacity of carbon monoxide per liter of VA per predicted measured by RB (RB-DLCO/VA%pred) in the 3 groups, respectively. Comparisons between 2 groups were performed by using the independent-sample t test, among more than 2 groups by using the One-Way ANOVA test, while the ROC curve was used to calculate the area under curve (AUC) and its 95%CI. RESULTS: In the control group, 15 subjects' RB-DLCO%pred was lower than 80%, and the mean value (78.8 ± 2.1)% was also lower than 80%. Using SB-DLCO%pred of the normal group as a standard to adjust the RB-DLCO%pred, the corrected value was 1.097, and then this value was used to adjust RB-DLCO/VA%pred in the 3 groups, respectively. Before correction DLCO%pred [the control group: (91.2 ± 1.9)% vs (78.8 ± 2.1)%; the ILD group: (45.8 ± 2.6)% vs (60.0 ± 1.9)%;the COPD group: (66.3 ± 2.9)% vs (56.6 ± 1.6)%]and DLCO/VA%pred [the control group: (99.8 ± 2.3)% vs (84.6 ± 4.5)%; the ILD group: (75.9 ± 3.0)% vs (88.5 ± 5.4)%; the COPD group: (80.2 ± 3.7)% vs (50.6 ± 2.5)% ] between the SB and RB were statistically different among the 3 groups. After correction, only the DLCO%pred [(45.8 ± 2.6)% vs (65.8 ± 2.1)%], DLCO/VA%pred [ (75.9 ± 3.0)% vs (102.2 ± 6.2)%] of the ILD group and the DLCO/VA%pred [(80.2 ± 3.7) vs (58.3 ± 2.8)%] of the COPD group had significant difference between the 2 methods (t = -6.00-4.68, all P < 0.01) . The test time of re-breathing in the COPD group (106 ± 5) s was significant longer than that of the ILD group (73 ± 4) s and the control group (79 ± 5) s (F = 11.99, P < 0.01), and the correlation between DLCO/VA%pred and the test time(r = -0.661, P < 0.01) was higher than the relationship between DLCO%pred and the test time (r = -0.391, P < 0.01). Furthermore, in the ILD group, the area of RB-DLCO%pred under ROC was 0.893, 95%CI being 0.817-0.970. In the COPD group, the area of RB-DLCO/VA%pred under ROC was 0.895, 95%CI being 0.811-0.979. CONCLUSIONS: There were differences between re-breathing and single-breath in measuring diffusing capacity. The present predicted value of the re-breathing method needed further study to confirm its applicability. Re-breathing method was more consistent with the respiratory physiology, and might be a better method to detect diseased states.

Qualitative and quantitative prediction of food allergen epitopes based on machine learning combined with in vitro experimental validation.

An allergen epitope is a part of molecules that can specifically bind to immunoglobulin E (IgE), causing an allergic reactions. To predict protein epitopes and their binding ability to IgE, quantitative structure-activity relationship (QSAR) models were established using four algorithms combined with the selected chemical descriptors. The model predicted the binding capabilities of the epitopes to IgE with the R2 and root mean squared error (RMSE) as 0.7494 and 0.2375, respectively. The model's performance was validated using an enzyme-linked immunosorbent assay (ELISA). The results showed that the established QSAR model could efficiently and accurately predict the allergic reaction of food protein epitopes. The prediction results of the model and the experimental results were consistent, with a Pearson correlation coefficient of 0.8956. The results from both the QSAR model and in vitro experiments indicated that amino acid sequence 116-130 was a novel IgE-binding epitope of ß-LG.

The default and directed pathways of hepatoblast differentiation involve distinct epigenomic mechanisms.

The effectiveness of multiomics analyses in defining cell differentiation pathways during development is ambiguous. During liver development, hepatoblasts follow a default or directed pathway to differentiate into hepatocytes or cholangiocytes, respectively, and this provides a practical model to address this issue. Our study discovered that promoter-associated histone modifications and chromatin accessibility dynamics, rather than enhancer-associated histone modifications, effectively delineated the "default vs. directed" process of hepatoblast differentiation. Histone H3K27me3 on bivalent promoters is associated with this asymmetric differentiation strategy in mice and humans. We demonstrated that Ezh2 and Jmjd3 exert opposing regulatory roles in hepatoblast-cholangiocyte differentiation. Additionally, active enhancers, regulated by P300, correlate with the development of both hepatocytes and cholangiocytes. This research proposes a model highlighting the division of labor between promoters and enhancers, with promoter-associated chromatin modifications governing the "default vs. directed" differentiation mode of hepatoblasts, whereas enhancer-associated modifications primarily dictate the progressive development processes of hepatobiliary lineages.

Preparation of fat substitute based on maize starch hydrolysates and application in reduced-fat acidified milk gel.

Reduced-fat food has become a popular choice among contemporary consumers. This study aims to develop a starch-based fat substitute and incorporate it into reduced-fat milk gel acidified with glucono-δ-lactone (GDL) to achieve similar rheological properties as a full-fat gel. The gel properties of the fat substitute were assessed. The study examined the rheological properties, syneresis, textural properties and microstructure of acidified milk gels while also monitoring acidification process. Starch hydrolysates with low dextrose equivalent (DE) (<5.1 %) can serve as an effective fat substitute due to their excellent gelling properties The rheological and textural properties of the reduced-fat acidified milk gel with DE at 3.1 % of starch hydrolysate and 30 % fat substitution are similar to those of the full-fat milk gel. The syneresis and confocal laser scanning microscopy (CLSM) results indicated that the microstructure of the reduced-fat acidified milk gel was similar to the full-fat version. Moreover, the sensory properties of the reduced-fat acidified milk gel were acceptable when the DE was 3.1 %, and 30 % fat was replaced. In our study, we utilized hydrolyzed starch to produce reduced-fat acidified milk gels, which could potentially be used in the development of reduced-fat yogurt formulations.

Identifying misconceptions and knowledge gaps in functional neurological disorders among emergency care providers.

BACKGROUND: Functional Neurologic Disorders (FND) are a common but heterogeneous group of disabling conditions. The Emergency Department (ED) is an important venue for care and referral as it is often the first point of contact when patients with FND are faced with a crisis or exacerbation of symptoms. METHODS: ED providers (n = 273) practicing in the Cleveland Clinic Foundation Northeast Ohio network were invited to participate through secure web application electronic surveys. Data were collected on practice profiles, knowledge, attitudes, management of FND, and awareness of available resources for FND. RESULTS: Sixty providers completed the survey (22% response rate; n = 50 ED physicians, 10 advanced care providers) with 95.0% (n = 57) reporting a lack of understanding about FND. The terms Psychogenic Nonepileptic Seizures and stress induced/stress related disease were used by 60.0% (n = 36) and 58.3% (n = 35) respectively. Ninety percent (n = 53) rated their experience with managing FND patients as at least more difficult. Eighty- five percent (n = 51) agreed with "rule out others" and 60% (n = 36) agreed with "caused by psych stress". Eighty six percent (n = 50) believe that there is a difference between FND from malingering. Only one respondent was familiar with any FND resources and 79% (n = 47) reported the need for FND specific educational materials. CONCLUSION: This survey revealed major gaps in knowledge, inaccurate perceptions, and management that differs from the current standard of care among ED providers caring for patients with FND. Educational opportunities are needed to guide diagnosis and evidence-based treatment to optimize management of patients with FND.

Study on potential antigenicity and functional properties of whey protein treated by high hydrostatic pressure based on structural analysis.

High hydrostatic pressure (HHP) is extensively utilized in the field of food processing due to its remarkable ability to preserve the freshness of food. The potential antigenicity of ß-lactoglobulin (ß-LG) in whey protein isolate (WPI, 3%) treated by HHP was detected by enzyme linked immunosorbent assay (ELISA) using monoclonal antibodies. Furthermore, the impact of pressure-induced structural alterations on the emulsification properties and antioxidant activity of WPI was investigated. The findings revealed that pressures exceeding 300 MPa resulted in molecular aggregation, the formation of inter-molecular disulfide bonds, and an increase in surface hydrophobicity (H0). The percentage of ß-sheet decreased along with the pressure. The results showed the increment of α-helix and ß-turn with pressure. ELISA demonstrated a significant reduction in the antigenicity of ß-LG following HHP treatment (100-600 MPa), with a slight recovery observed at 300 MPa. These spatial structural modifications led to the unfolding of the ß-LG molecule, thereby enhancing its digestibility. Moreover, HHP treatment substantially improved the antioxidant properties, with the exposure to hydrophobic amino acids contributing to increased antioxidant properties and emulsion stability.

A hydrostable CuII coordination network prepared hydrothermally as a "turn-on" fluorescent sensor for S2- and a selective adsorbent for methylene blue.

The effective monitoring of water pollution and further purification are pressing yet challenging issues for guaranteeing the health of human beings and the stabilization of ecological systems. For this purpose, the development of efficient sensing and adsorption materials as a result of supramolecular interactions, including coordination and H-bonding etc., have been attracting increasing attention. With the aid of a coordination-driven self-assembly strategy, a new nonporous 2D CuII coordination network, [Cu2L(H2O)2]n (donated as CuCP), based on H4L, where H4L = 4-(4-(3,5-di-carboxy-pyridin-4-yl)phenyl)pyridine-2,6-dicarboxylic acid, was afforded hydrothermally. Structural analysis indicated that CuCP featured a wrinkled network similar to the ancient Chinese folding screens and constructed by the fully deprotonated ligand L4- with the coordination mode of bis(µ2-η1:η1:η2) and penta-coordinated Cu2+, which could be further upgraded to a supramolecular 3D framework as a result of the synergism of multiple C-H⋯O hydrogen bonds. The hydrostability of CuCP could be maintained within a wide pH range from 2 to 12 as verified by PXRD determination, endowing it with potential environmental applications. Thanks to the combination of the soft Lewis acidity of Cu2+ and its large conjugated structure, CuCP could be used as a turn-on fluorescence sensor for S2- and exhibited a different fluorescence response when Na2S, (NH4)2S or H2S were incorporated, even in actual water samples. The sensing mechanisms were disclosed in detail by the combination of experiments and density functional theory (DFT) calculations. Furthermore, CuCP was shown to be a selective and recoverable adsorbent with a maximum adsorption capacity of 379 mg g-1 in 60 minutes for methylene blue (MB). The adsorption mechanism could be a combination of π⋯π stacking, n⋯π interaction, aggregation effects and Soft and Hard Acid-Base theory (HSAB). The results presented herein open up new perspectives for CuII species in environmental applications.

Dopamine agonist withdrawal syndrome associated factors: A retrospective chart review.

Dopamine agonist withdrawal syndrome (DAWS) has been introduced to describe the constellation of symptoms resulting from reduction or suspension of dopamine agonist medications. In patients with Parkinson's disease (PD) the impact of DAWS can be significant in terms of distress and disability. Unfortunately, no standard treatment exists other than reintroduce the dopamine agonist even in the presence of adverse effects. Therefore, identification of vulnerable patients would be beneficial. Previous studies have linked DAWS with impulse control disorder behavior (ICD), higher dopamine agonist doses, and milder motor impairment in PD patients. We conducted a retrospective chart review of PD patients treated with dopamine agonist. A total of 313 charts from January 2011 to December 2013 were reviewed, showing 126 patients who were discontinued from dopamine agonist. Twenty-one patients (16.8 %) fulfilled the diagnostic criteria for DAWS. Factors associated with the occurrence of DAWS were: (1) dose of dopamine agonist ≥150 mg expressed in levodopa equivalents daily dose (LEDD) (p = 0.018), (2) impulse control disorder as an adverse effect to dopamine agonist (p = 0.002), and (3) prior deep brain stimulation (DBS) (p = 0.049). The probability of developing DAWS in the presence of all 3 identified factors was 92 %; presence of 2 factors raised the probability up to 70 %; the presence of one factor increased the probability up to 30 %. In the absence of these 3 factors the probability of developing DAWS was 3 %. Prospective studies are warranted to confirm these findings.

A novel computed tomography angiography technique: guided preoperative localization and design of anterolateral thigh perforator flap.

BACKGROUND: Anterolateral thigh perforator (ALTP) flap is considered a versatile flap for soft tissue reconstruction. Computed tomography angiography (CTA) is used for mapping perforator in abdominal-based reconstruction; however, it is less commonly used in ALTP due to its poor imaging efficacy. In this study, we introduced a novel CTA technique for preoperative localization and design of ALTP flap and evaluated its value in directing surgical reconstruction. RESULTS: Thirty-five patients with soft tissue defects were consecutively enrolled. Modified CTA procedures, such as sharp convolution kernel, ADMIRE iterative reconstruction, 80 kV tube voltage, high flow contrast agent and cinematic rendering image reconstruction, were used to map ALTPs. A total of 287 perforators (including 884 sub-branches) were determined, with a mean of 5 perforators per thigh (range 2-11). The ALTPs were mainly concentrated in the "hot zone" (42%, 121/287) or the distal zone (41%, 118/287). Most perforators originated from the descending branch of the lateral circumflex femoral artery (76%, 219/287). Three perforator types, namely musculocutaneous (62%, 177/287), septocutaneous (33%, 96/287), and mixed pattern (5%, 14/287), were identified. The median pedicle length measured by two methods was 4.1 cm (range 0.7-20.3 cm) and 17.0 cm (range 4.7-33.9 cm), respectively, and the median diameter of the skin flap nourished by one perforator was 3.4 cm (IQR 2.1-5.7 cm). Twenty-eight ALTP flaps were obtained with the guidance of CTA, and 26 flaps survived after follow-up. CONCLUSIONS: The proposed CTA mapping technique is a useful tool for preoperative localization and design of ALTP flap.