Differential Upregulation of Th1/Th17-Associated Proteins and PD-L1 in Granulomatous Mycosis Fungoides.

Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid population and is considered to have a worse prognosis compared with regular MF. The upregulation of the T helper (Th) axis, especially Th17, plays an important role in the pathogenesis of several inflammatory/infectious granulomatous cutaneous diseases, but its role in GMF is still not elucidated to date. In this study, we evaluated the immunohistochemical expression of Th1 (Tbet), Th2 (GATA-3), Th17 (RORγT), T regulatory (Foxp3), and immune checkpoint (IC) (PD-1 and PD-L1) markers in a cohort of patients with GMF and MF with large cell transformation (MFLCT). Skin biopsies from 49 patients (28 GMF and 21 MFLCT) were studied. Patients with GMF were associated with early clinical stage (p = 0.036) and lower levels of lactate dehydrogenase (p = 0.042). An increased percentage of cells positive for Tbet (p = 0.017), RORγT (p = 0.001), and PD-L1 (p = 0.011) was also observed among the GMF specimens, while a stronger PD-1 intensity was detected in cases of MFLCT. In this cohort, LCT, RORγT < 10%, Foxp3 < 10%, age, and advanced stage were associated with worse overall survival (OS) in univariate analysis. GMF demonstrated Th1 (cellular response) and Th17 (autoimmunity) phenotype, seen in early MF and granulomatous processes, respectively, which may be related to the histopathological appearance and biological behavior of GMF. Further studies involving larger series of cases and more sensitive techniques are warranted.

Parkinson's Disease Dementia Patients: Expression of Glia Maturation Factor in the Brain.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease characterized by the presence of dopaminergic neuronal loss and motor disorders. PD dementia (PDD) is a cognitive disorder that affects many PD patients. We have previously demonstrated the proinflammatory role of the glia maturation factor (GMF) in neuroinflammation and neurodegeneration in AD, PD, traumatic brain injury (TBI), and experimental autoimmune encephalomyelitis (EAE) in human brains and animal models. The purpose of this study was to investigate the expression of the GMF in the human PDD brain. We analyzed the expression pattern of the GMF protein in conjunction with amyloid plaques (APs) and neurofibrillary tangles (NFTs) in the substantia nigra (SN) and striatum of PDD brains using immunostaining. We detected a large number of GMF-positive glial fibrillary acidic protein (GFAP) reactive astrocytes, especially abundant in areas with degenerating dopaminergic neurons within the SN and striatum in PDD. Additionally, we observed excess levels of GMF in glial cells in the vicinity of APs, and NFTs in the SN and striatum of PDD and non-PDD patients. We found that the majority of GMF-positive immunoreactive glial cells were co-localized with GFAP-reactive astrocytes. Our findings suggest that the GMF may be involved in the pathogenesis of PDD.

Detection of azadirachtin from neem kernels using a paper-based sandwich sensor.

In this work, a microfluidic paper-based analytical device (µPAD) was developed to detect the biopesticide azadirachtin (Aza) through a colorimetric assay. High precision estimation of Aza is classically carried out using high performance liquid chromatography (HPLC), which requires highly skilled personnel. Acidified vanillin is a commonly used colorimetric indicator in thin layer chromatography for detection of various phytochemicals. However, the assay involves concentrated acid, which limits the choice of paper substrates for paper-based sensors and raises safety concerns. In this work, we show how the assay can be extended from the liquid phase to a paper substrate. Glass microfiber (GMF) filter paper was found to be suitable paper as it was acid resistant; besides, its hydrophilicity enabled smooth flow of reagents. A microfluidic paper-based sensor (µPAD) was developed by sandwiching 5 mm sized GMF dots between two parafilm sheets. We demonstrate the use of colorimetric assay on the µPAD for on-site detection of Aza in neem kernels. The magenta color developed upon the reaction of acidified vanillin with Aza was captured using a smart-phone and analysed using RGB levels in the image. Calibration was established using neem kernel extract of known concentration. Linearity was seen in the concentration range of 5 to 25 mg L-1 Aza. A limit of detection of 2.3 mg L-1 was obtained using this method. The colorimetric assay showed a relative recovery of >85% when compared with the values obtained from HPLC. The stability of the reagents on the GMF sensor was investigated to understand the storage conditions and shelf life of the reagents and sensor. The present work demonstrates the development of a portable sensor for on-site detection of phytochemicals that can be an integral part of the agricultural supply chain.

Avian navigation: the geomagnetic field provides compass cues but not a bicoordinate "map" plus a brief discussion of the alternative infrasound direction-finding hypothesis.

The geomagnetic field (GMF) is a worldwide source of compass cues used by animals and humans alike. The inclination of GMF flux lines also provides information on geomagnetic latitude. A long-disputed question, however, is whether horizontal gradients in GMF intensity, in combination with changes in inclination, provide bicoordinate "map" information. Multiple sources contribute to the total GMF, the largest of which is the core field. The ubiquitous crustal field is much less intense, but in both land and marine settings is strong enough at low altitudes (< 700 m; sea level) to mask the core field's weak N-S intensity gradient (~ 3-5 nT/km) over 10 s to 100 s of km. Non-orthogonal geomagnetic gradients, the lack of consistent E-W gradients, and the local masking of core-field intensity gradients by the crustal field, therefore, are grounds for rejection of the bicoordinate geomagnetic "map" hypothesis. In addition, the alternative infrasound direction-finding hypothesis is briefly reviewed. The GMF's diurnal variation has long been suggested as a possible Zeitgeber (timekeeper) for circadian rhythms and could explain the GMF's non-compass role in the avian navigational system. Requirements for detection of this weaker diurnal signal (~ 20-50 nT) might explain the magnetic alignment of resting and grazing animals.

Direct observation of cortactin protecting Arp2/3-actin filament branch junctions from GMF-mediated destabilization.

How cells tightly control the formation and turnover of branched actin filament arrays to drive cell motility, endocytosis, and other cellular processes is still not well understood. Here, we investigated the mechanistic relationship between two binding partners of the Arp2/3 complex, glia maturation factor (GMF) and cortactin. Individually, GMF and cortactin have opposite effects on the stability of actin filament branches, but it is unknown how they work in concert with each other to govern branch turnover. Using TIRF microscopy, we observe that GMF's branch destabilizing activities are potently blocked by cortactin (IC50 = 1.3 nM) and that this inhibition requires direct interactions of cortactin with Arp2/3 complex. The simplest model that would explain these results is competition for binding Arp2/3 complex. However, we find that cortactin and GMF do not compete for free Arp2/3 complex in solution. Further, we use single molecule analysis to show that cortactin's on-rate (3 ×107 s-1 M-1) and off-rate (0.03 s-1) at branch junctions are minimally affected by excess GMF. Together, these results show that cortactin binds with high affinity to branch junctions, where it blocks the destabilizing effects of GMF, possibly by a mechanism that is allosteric in nature. In addition, the affinities we measure for cortactin at actin filament branch junctions (Kd = 0.9 nM) and filament sides (Kd = 206 nM) are approximately 20-fold stronger than previously reported. These observations contribute to an emerging view of molecular complexity in how Arp2/3 complex is regulated through the integration of multiple inputs.

G9a Inhibition Promotes Neuroprotection through GMFB Regulation in Alzheimer's Disease.

Epigenetic alterations are a fundamental pathological hallmark of Alzheimer's disease (AD). Herein, we show the upregulation of G9a and H3K9me2 in the brains of AD patients. Interestingly, treatment with a G9a inhibitor (G9ai) in SAMP8 mice reversed the high levels of H3K9me2 and rescued cognitive decline. A transcriptional profile analysis after G9ai treatment revealed increased gene expression of glia maturation factor ß (GMFB) in SAMP8 mice. Besides, a H3K9me2 ChIP-seq analysis after G9a inhibition treatment showed the enrichment of gene promoters associated with neural functions. We observed the induction of neuronal plasticity and a reduction of neuroinflammation after G9ai treatment, and more strikingly, these neuroprotective effects were reverted by the pharmacological inhibition of GMFB in mice and cell cultures; this was also validated by the RNAi approach generating the knockdown of GMFB/Y507A.10 in Caenorhabditis elegans. Importantly, we present evidence that GMFB activity is controlled by G9a-mediated lysine methylation as well as we identified that G9a directly bound GMFB and catalyzed the methylation at lysine (K) 20 and K25 in vitro. Furthermore, we found that the neurodegenerative role of G9a as a GMFB suppressor would mainly rely on methylation of the K25 position of GMFB, and thus G9a pharmacological inhibition removes this methylation promoting neuroprotective effects. Then, our findings confirm an undescribed mechanism by which G9a inhibition acts at two levels, increasing GMFB and regulating its function to promote neuroprotective effects in age-related cognitive decline.

The ameliorative effects of topical gemifloxacin alone or in combination with clobetasol propionate on imiquimod-induced model of psoriasis in mice.

Psoriasis is a lifelong immune-driven skin condition characterized by excessive epidermal overgrowth and inflammatory cell infiltration. Gemifloxacin is a fourth-generation fluoroquinolone with improved immunomodulatory and anti-inflammatory properties that are believed to possess an attractive role in psoriasis via suppressing the production of cytokines, chemokines, and eosinophil and neutrophil chemotaxis. The aim of this research is to investigate the ameliorative effects of prolonged topical gemifloxacin (GMF) alone and combined with clobetasol propionate (CLO) on an imiquimod (IMQ)-induced mouse model of psoriasis. Forty-eight Swiss albino mice were divided into six groups of eight. All groups except the negative controls got 62.5 mg of IMQ 5% topically for 8 days. Mice in the control group (controls) got Vaseline instead. Following the induction in the IMQ 5% group, mice in treatment groups CLO 0.05, GMF 1%, GMF 3%, and CLO + GMF obtained clobetasol propionate 0.05%, GMF 1% and 3%, and a combination of both, respectively, for an additional 8 days, rendering the experiment 16 days long. Our results revealed that gemifloxacin alleviated erythematous, thickened, and scaly psoriatic lesions and inhibited the tissue level of inflammatory cytokines, including interleukin (IL)-8, IL-17A, IL-23, tumor necrosis factor-α (TNF-α), and transforming growth factor-ß1 (TGF-ß1). The anti-inflammatory effect also occurred by hindering nuclear factor-kappa B (NF-κB) signaling and reversing histopathological problems. Gemifloxacin acts effectively in mitigating psoriasis-associated lesions and restricting NF-κB-mediated inflammation, recommending gemifloxacin as a promising adjuvant candidate for additional studies on the long-term treatment of autoimmune and autoinflammatory dermatoses like psoriasis.

Mycosis Fungoides and Granulomatous Slack Skin: A Single Entity With Distinct Clinical Phenotypes.

ABSTRACT: Granulomatous cutaneous T-cell lymphoma includes mycosis fungoides with significant granulomatous inflammation (GMF) and granulomatous slack skin (GSS), listed in the WHO classification as a subtype of mycosis fungoides (MFs). 1 These overlapping entities have shared clinical and histopathologic features which can present a diagnostic challenge. The dominance of the granulomatous infiltrate and the often sparse lymphocytic infiltrate frequently with minimal cytological atypia are features that distract from the correct diagnosis, even when raised by the clinician. We describe the clinical and histopathologic characteristics of 3 cases of granulomatous cutaneous T-cell lymphoma, illustrate the close clinical and pathologic relationship between GMF and GSS and emphasize the diagnostic difficulties that the granulomatous infiltrate can present. Furthermore, we demonstrate, for the first time, considerable elastolysis in a significant proportion of classical (Alibert-Bazin) MF lesions and therefore postulate that the differences observed between GMF and GSS are one of degree and secondary to their anatomic location rather than reflecting meaningful separate entities.

Effect of physical training on motor function of ambulant children with diplegia after selective dorsal rhizotomy: A randomized controlled study.

BACKGROUND: Children with spastic diplegia experience tonicity, lack of selective motor control, subnormal postural stability and delayed motor development. Selective dorsal rhizotomy followed by physical therapy is a permanent procedure aimed to alleviate hypertonicity. OBJECTIVE: To explore the efficacy of selective dorsal rhizotomy (SDR) followed by a physical training on gross motor function (GMF), functional balance, walking capacity, selective motor control (SMC) and energy cost of walking (ECW) of ambulant children with spastic diplegia. METHODS: Forty-two children with spastic diplegia aged 5 to 8 years were randomly assigned into the control or SDR-group. Both groups received a designed physical training of progressive functional strength training and standard orthotic management (SOM) 3 times a week for 6 months. GMF, functional balance, ECW, functional capacity and SMC were assessed by gross motor function measure (GMfM-88), pediatric balance scale (PBS), energy expenditure index (EEI), six-minute walking test (6MWT) and selective control assessment of lower extremity (SCALE), respectively. Assessment was carried out before the treatment (baseline), after 6 months (post I) and 1-year follow-up (post II). RESULTS: From baseline to post I and post II assessments, changes of GMF, functional balance, ECW, functional capacity and SMC within the control and SDR groups showed significant improvements (P < 0.001). Moreover, group comparison showed significant differences in favor of the SDR group. CONCLUSION: Integrated physical training followed SDR demonstrated qualitative changes and enhancement in motor function, achieved by spasticity reduction.

Whole Goat Milk-Based Formula versus Whey-Based Cow Milk Formula: What Formula Do Infants Enjoy More?-A Feasibility, Double-Blind, Randomized Controlled Trial.

(1) Background: While goat milk formula (GMF) is an alternative to cow milk formula (CMF), infants' preferences for one over the other have not been formally assessed. Specifically, our aim in this study was to determine whether infants experience fewer feeding behavior problems with whole milk-based GMF than with conventional whey-based CMF. (2) Methods: This was a multicenter, double-blind, randomized controlled trial with two-arm parallel assignment conducted in six pediatricians' offices in or near Paris, France, between June 2018 and 31 December 2021. Overall, 64 healthy infants (≤4 months old), predominantly formula-fed, were randomly assigned to either the whole milk-based GMF (n = 33) or whey-based CMF (n = 31) arm. Parents completed the Baby Eating Behavior Questionnaire (BEBQ) and the modified QUALIN questionnaire to evaluate infant feeding behavior and quality of life (psychomotor and socioemotional development), respectively, at inclusion (1 to 5 days before milk delivery) and the final visit (day 28 ± 3 after milk delivery). Informed consent was obtained for all recruited patients, and an ethical committee approved the study. (3) Results: Changes in BEBQ Enjoyment of Food and Slowness in Eating subscale scores from inclusion to final visit did not differ between arms. However, there were significant improvements in subscale scores for Food Responsiveness (GMF: 0.15 ± 1; CMF: -0.48 ± 0.81; p = 0.010) and General Appetite (GMF: 0.26 ± 1.2; CMF: -0.48 ± 0.88; p = 0.012), and modified QUALIN (GMF: 4.6 ± 9.4; CMF: -0.40 ± 7.6; p = 0.03) scores in favor of the GMF group. (4) Conclusions: In this double-blind, randomized controlled trial, GMF-fed infants exhibited a greater general appetite than CMF-fed infants, possibly due to differences in the composition of these formulas (i.e., protein and lipid profiles). In addition, GMF-fed infants enjoyed a better quality of life. There was no difference in food enjoyment between groups. These findings suggest that whole-milk-based GMF could be an attractive alternative to whey-based CMF. Clinical trial registration: NCT03488758 (clinicaltrials.gov).

Correlations between geomagnetic field and global occurrence of cardiovascular diseases: evidence from 204 territories in different latitude.

BACKGROUND: The correlation between stable geomagnetic fields and unstable geomagnetic activities with mortality, incidence, and prevalence of cardiovascular diseases (CVDs) remains ambiguous. METHOD: To investigate the correlations between geomagnetic field (GMF) intensity and geomagnetic disturbance (GMD) and CVDs events in global, long-period scale, global and 204 countries and territories were included on the base of 2019 Global Burden of Disease study (GBD 2019). Data of GMF intensity, GMD frequency, CVDs events, weather and health economic indicators from 1996 to 2019 of included locations were collected. Linear regression and panel data modelling were conducted to identify the correlations between GMF intensity and CVDs events, multi-factor panel data analysis was also generated to adjust the effect of confounding factors. RESULTS: For the average data during 1996-2019, linear regression model revealed consistent positive correlations between total GMF (tGMF) intensity and mortality of total CVDs [coef = 0.009, (0.006,0.011 95%CI)], whereas negative correlations were found between horizonal GMF (hGMF) intensity and total CVD mortality [coef = -0.010 (-0.013, -0.007 95%CI)]. When considering the time trend, panel data analysis still demonstrated positive correlation between tGMF and total CVDs mortality [coef = 0.009, (0.008,0.009 95%CI)]. Concurrently, the hGMF negatively correlated with total CVDs mortality [coef = -0.008, (-0.009, -0.007 95%CI)]. When the panel models were adjusted for confounding factors, no reverse of correlation tendency was found between tGMF, hGMF and CVDs events. In high-income territories, positive correlation was found between geomagnetic storm (GMS) frequency and mortality of total CVDs [coef = 14.007,(2.785, 25.229 95%CI)], however, this positive trend faded away gradually with the latitude decreasing from polar to equator. CONCLUSIONS: Stable and long-term horizontal component of GMF may be beneficial to cardiac health. Unstable and short-term GMF called GMD could be a hazard to cardiac health. Our results suggest the importance of regular GMF in maintaining cardio-health state and the adverse impacts of GMD on cardiac health.

Gluteus maximus transfer for wound closure and treatment of abductor deficiency: a single-plastic surgeon series.

INTRODUCTION: Due to the increasing number of total hip arthroplasties (THA), the number and complexity of revision procedures are also on the rise. For complex cases such as periprosthetic joint infections with soft tissue compromise or for abductor muscle deficiencies, one of the treatment options is a gluteus maximus flap (GMF) that covers dead space and can help restore the failed abductor mechanism. The purpose of this study is to investigate the outcomes of a single-plastic surgeon's series of GMF procedures. MATERIALS AND METHODS: This retrospective review reports on 57 patients (mean follow-up 39.2 months) undergoing GMF transfers for abductor insufficiency on native hip (N = 16), for abductor insufficiency in aseptic revision THA (rTHA) (N = 16), for soft tissue defects in aseptic rTHA (N = 8) and for soft tissue defects in septic rTHA (N = 17) by a single plastic surgeon over a 10-year period. Revision-free survival and complication rates were assessed and risk factors were analyzed with Cox-regression analysis. RESULTS: The reoperation-free survival rate of GMF for abductor insufficiency in native hips was 100%. GMF procedures for soft tissue defects in septic rTHA had the lowest cumulative revision-free survival (34.3%) and highest reinfection rates (53.9%). More than three prior surgeries (HR = 2.9, p = 0.020), presence of infection (HR = 3.2, p = 0.010) and resistant organisms (HR = 3.1, p = 0.022) significantly increased the risk of revision. CONCLUSIONS: GMF is a viable option for addressing abductor insufficiency in native hip joints. However, high revision and complication rates are reported for GMF in septic rTHA. This study highlights the need to clarify the circumstances for which the flap reconstruction will be indicated.

Granulomatous mural folliculitis in 16 domestic goats: Infection with malignant catarrhal fever viruses and colocalization with ovine herpesvirus-2 using in situ hybridization.

Granulomatous mural folliculitis (GMF) is an uncommon reaction pattern occasionally observed in nonadapted ruminant hosts infected with malignant catarrhal fever viruses. This report characterizes GMF and concurrent cutaneous lesions in 16 goats with crusting dermatitis using histochemistry including hematoxylin and eosin, periodic acid-Schiff, and Grocott's methenamine silver, and immunohistochemistry for CD3, CD20, ionized calcium binding adaptor molecule 1, and cytokeratin AE1/3. Infiltrates in all 16 GMF cases consisted of macrophages and fewer T lymphocytes, and variably included eosinophils, multinucleated histiocytic giant cells, and/or neutrophils. Formalin-fixed paraffin-embedded skin and fresh skin samples from caprine GMF cases were tested using pan-herpesvirus nested conventional polymerase chain reaction (PCR) and partial sequencing, ovine herpesvirus-2 (OvHV-2) real-time PCR, and OvHV-2 colorimetric in situ hybridization (ISH). Five of 16 goats with GMF (31%) were PCR positive for malignant catarrhal fever viruses, including caprine herpesvirus 3 in 1 goat and OvHV-2 in 4 goats. Three goats also had positive intranuclear OvHV-2 hybridization signal in follicular keratinocytes, among other cell types, localized to areas of GMF. Herpesviruses were not detected in the formalin-fixed paraffin-embedded skin of 9 goats without GMF. This case series describes relatively frequent detections of malignant catarrhal fever viruses in the skin of goats with GMF, including the first report of caprine herpesvirus 3, and localizes OvHV-2 infected follicular keratinocytes within areas of GMF.

Cellulose ether treatment inhibits amyloid beta aggregation, neuroinflammation and cognitive deficits in transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is an incurable, progressive and devastating neurodegenerative disease. Pathogenesis of AD is associated with the aggregation and accumulation of amyloid beta (Aß), a major neurotoxic mediator that triggers neuroinflammation and memory impairment. Recently, we found that cellulose ether compounds (CEs) have beneficial effects against prion diseases by inhibiting protein misfolding and replication of prions, which share their replication mechanism with Aß. CEs are FDA-approved safe additives in foods and pharmaceuticals. Herein, for the first time we determined the therapeutic effects of the representative CE (TC-5RW) in AD using in vitro and in vivo models. Our in vitro studies showed that TC-5RW inhibits Aß aggregation, as well as neurotoxicity and immunoreactivity in Aß-exposed human and murine neuroblastoma cells. In in vivo studies, for the first time we observed that single and weekly TC-5RW administration, respectively, improved memory functions of transgenic 5XFAD mouse model of AD. We further demonstrate that TC-5RW treatment of 5XFAD mice significantly inhibited Aß oligomer and plaque burden and its associated neuroinflammation via regulating astrogliosis, microgliosis and proinflammatory mediator glial maturation factor beta (GMFß). Additionally, we determined that TC-5RW reduced lipopolysaccharide-induced activated gliosis and GMFß in vitro. In conclusion, our results demonstrate that CEs have therapeutic effects against Aß pathologies and cognitive impairments, and direct, potent anti-inflammatory activity to rescue neuroinflammation. Therefore, these FDA-approved compounds are effective candidates for developing therapeutics for AD and related neurodegenerative diseases associated with protein misfolding.

The Effect of Goat-Milk-Based Infant Formulas on Growth and Safety Parameters: A Systematic Review and Meta-Analysis.

Goat-milk-based infant formulas (GMFs) are now available in several countries, having been approved by authorities. We systematically evaluated the effects of GMF compared with cow-milk-based formula (CMF) on infant growth and safety parameters. The MEDLINE, EMBASE, and Cochrane Library databases were searched (December 2022) for randomized controlled trials (RCTs). The risk of bias was assessed using the Revised Cochrane Risk-of-Bias tool (ROB-2). Heterogeneity was quantified by I2. Four RCTs involving a total of 670 infants were identified. All trials revealed some concern in ROB-2. Furthermore, all of the included studies were funded by the industry. Compared with infants fed CMF, those fed GMF showed similar growth in sex- and age-adjusted z-scores for weight (mean difference, MD, 0.21 [95% confidence interval, CI, -0.16 to 0.58], I2 = 56%), length (MD 0.02, [95% CI -0.29 to 0.33], I2 = 24%), and head circumference (MD 0.12, 95% [CI -0.19 to 0.43], I2 = 2%). Stool frequency was similar among the groups. Due to differences in the reporting of stool consistency, no firm conclusion can be drawn. Adverse effects (serious or any) were similar in both groups. These findings provide reassurance that GMFs compared with CMFs are safe and well tolerated.

CaTiO3/g-C3N4 heterojunction-based composite photocatalyst: Part I: Experimental design, kinetics, and scavenging agents' effects in photocatalytic degradation of gemifloxacin.

A critical, challenging environmental issue is explored pollution of water supplies by discharging industrial/pharmaceutical/hospital/urban wastewaters into the aquatic environment. These needs introducing/developing novel photocatalysts/adsorbents/procedures for removing or mineralizing various pollutants in wastewater before discharging them into marine environments. Further, optimizing conditions to achieve the highest removal efficiency is an important issue. In this study, CaTiO3/g-C3N4 (CTCN) heterostructure was synthesized and characterized by some identification techniques. The simultaneous interaction effects of the experimental variables on the boosted photocatalytic activity of CTCN in the degradation of gemifloxcacin (GMF) were studied in RSM design. The optimal values for four parameters were: catalyst dosage: 0.63 g L-1, pH: 6.7, CGMF: 1 mg L-1, and irradiation time: 27.5 min, with approximately 78.2% of degradation efficiency. The quenching effects of the scavenging agents were studied to show the reactive species' relative importance in GMF photodegradation. The results illustrate that the reactive •OH plays a significant role, and the electron plays a minor role in the degradation process. The direct Z-scheme mechanism better described the photodegradation mechanism due to the great oxidative and reductive abilities of prepared composite photocatalysts. This mechanism is an approach to efficiently separating photogenerated charge carriers and improving the CaTiO3/g-C3N4 composite photocatalyst activity. The COD has been performed to study the details of the mineralization of GMF. The pseudo-first-order rat (from the Hinshelwood model) constants of 0.046 min-1 (t1/2 = 15.1 min) and 0.048 min-1 (t1/2 = 14.4 min) were respectively obtained from the GMF photodegradation data and COD results. The prepared photocatalyst retained its activity after five reusing runs.

The impact of cigarette smoking on cognitive processing speed and brain atrophy in multiple sclerosis.

BACKGROUND: Smoking is associated with an increased risk of multiple sclerosis (MS) and disability worsening. The relationship between smoking, cognitive processing speed, and brain atrophy remains uncertain. OBJECTIVE: To quantify the impact of smoking on processing speed and brain volume in MS and to explore the longitudinal relationship between smoking and changes in processing speed. METHODS: A retrospective study of MS patients who completed the processing speed test (PST) between September 2015 and March 2020. Demographics, disease characteristics, smoking history, and quantitative magnetic resonance imaging (MRI) were collected. Cross-sectional associations between smoking, PST performance, whole-brain fraction (WBF), gray matter fraction (GMF), and thalamic fraction (TF) were assessed using multivariable linear regression. The longitudinal relationship between smoking and PST performance was assessed by linear mixed modeling. RESULTS: The analysis included 5536 subjects of whom 1314 had quantitative MRI within 90 days of PST assessment. Current smokers had lower PST scores than never smokers at baseline, and this difference persisted over time. Smoking was associated with reduced GMF but not with WBF or TF. CONCLUSION: Smoking has an adverse relationship with cognition and GMF. Although causality is not demonstrated, these observations support the importance of smoking cessation counseling in MS management.

Effect of acuity level and patient characteristics on bowel preparation quality: a retrospective cohort study of inpatient colonoscopies.

BACKGROUND AND AIMS: Colonoscopy is the primary method to detect mucosal abnormalities in the colon, rectum, and terminal ileum. Inadequate bowel preparation is a common problem and can impede successful visualization during colonoscopy. Although studies identified hospitalization as a predictor of inadequate bowel preparation, acuity of care vary greatly within this patient population. The current study aims to examine the effect of patient characteristics and care level predictors on inadequate bowel preparation quality within the inpatient setting. METHODS: This retrospective study was conducted in a single urban level 1 trauma medical center and included adult patients undergoing diagnostic colonoscopy while admitted in the hospital from January 1, 2015 to June 30, 2020. We examined the level of inpatient care between the General Medical Floor (GMF), Intensive Care Units (ICU) and Telemetry Unit (TU) and assessed this association with bowel preparation quality, adjusting for known and unknown predictors. RESULTS: Of 538 patients undergoing colonoscopy, 47.4% were admitted into TU, 43.7% into GMF and 8.9% into ICU. For the entire sample, 72.7% of patients achieved good or excellent preparation and quality of bowel preparation differed by care level (P = 0.01). Patients from the critical care units were less likely to achieve adequate bowel preparation when compared to GMF (Odds Ratio [OR] 0.36; 95% Confidence Interval [CI] 0.17,0.77), after adjusting for patient characteristics, medications, physical status, and preparation regimen. No significant difference in Bowel Preparation Quality (BPQ) was identified between patients from GMF and TU (OR 0.96; 95%CI 0.61, 1.52). Furthermore, adequate BPQ was associated with withdrawal time and cecal intubation, but not higher adenoma detection rates. CONCLUSIONS: Results suggest the ICU setting is an independent predictor for inadequate bowel preparation and patients with prior opioid and laxative use may be more likely to have inadequate bowel preparation in the hospital. Future interventions should prioritize preprocedural clinician meetings for critical care unit patients, including a more detailed readiness assessment and thorough medication history.

Highly-expressed circ_0129657 inhibits proliferation as well as promotes apoptosis and inflammation in HBMECs after oxygen-glucose deprivation via miR-194-5p/GMFB axis.

Stroke is an acute cerebrovascular disease that is now the most important cause of death due to brain problems in our country. CircRNAs are RNA circles that have been extensively involved in the disease. We aimed to investigate the mechanism of circ_0129657 in the pathogenesis of stroke. In this study, quantitative real-time polymerase chain reaction (RT-qPCR) and western blot assays were used to assess the expression of circ_0129657, miR-194-5p, and glia maturation factor beta (GMFB). Cell viability was measured by Cell Counting Kit-8 (CCK-8) assay. 5-Ethynyl-2'-Deoxyuridine (EdU) assay was used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis. Dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays were used to assess the relationship between miR-194-5p and circ_0129657 or GMFB. Mouse middle cerebral artery occlusion (MCAO) model was applied to mimic the cerebral ischemia/reperfusion injury. Our data showed that the levels of circ_0129657 and GMFB were significantly increased and the expression of miR-194-5p was significantly decreased in oxygen-glucose deprivation (OGD)-induced human brain microvascular endothelial cells (HBMECs). Silencing circ_0129657 expression in OGD-induced HBMECs could promote cell viability and cell proliferation. Moreover, circ_0129657 depletion also could inhibit apoptosis and inflammatory factor secretion. Circ_0129657 functioned as a sponge for miR-194-5p and could regulate GMFB expression via miR-194-5p competition. Furthermore, miR-194-5p downregulation or GMFB restoration could partially reverse the effects of circ_0129657 silencing on cell biological properties in OGD-induced HBMECs. Meanwhile, circ_0129657 knockdown decreased cerebral infarction volume and neurological impairment in MCAO mouse models. In conclusion, our findings suggest that circ_0129657 can inhibit cell proliferation and promote apoptosis and inflammatory factor secretion in HBMECs after oxygen-glucose deprivation via miR-194-5p/GMFB axis, providing evidence that circ_0129657 has the potential as a useful biological molecular marker in the diagnosis of stroke.

Glia maturation factor beta deficiency protects against diabetic osteoporosis by suppressing osteoclast hyperactivity.

Excessive osteoclast activation, which depends on dramatic changes in actin dynamics, causes osteoporosis (OP). The molecular mechanism of osteoclast activation in OP related to type 1 diabetes (T1D) remains unclear. Glia maturation factor beta (GMFB) is considered a growth and differentiation factor for both glia and neurons. Here, we demonstrated that Gmfb deficiency effectively ameliorated the phenotype of T1D-OP in rats by inhibiting osteoclast hyperactivity. In vitro assays showed that GMFB participated in osteoclast activation rather than proliferation. Gmfb deficiency did not affect osteoclast sealing zone (SZ) formation but effectively decreased the SZ area by decreasing actin depolymerization. When GMFB was overexpressed in Gmfb-deficient osteoclasts, the size of the SZ area was enlarged in a dose-dependent manner. Moreover, decreased actin depolymerization led to a decrease in nuclear G-actin, which activated MKL1/SRF-dependent gene transcription. We found that pro-osteoclastogenic factors (Mmp9 and Mmp14) were downregulated, while anti-osteoclastogenic factors (Cftr and Fhl2) were upregulated in Gmfb KO osteoclasts. A GMFB inhibitor, DS-30, targeting the binding site of GMFB and Arp2/3, was obtained. Biocore analysis revealed a high affinity between DS-30 and GMFB in a dose-dependent manner. As expected, DS-30 strongly suppressed osteoclast hyperactivity in vivo and in vitro. In conclusion, our work identified a new therapeutic strategy for T1D-OP treatment. The discovery of GMFB inhibitors will contribute to translational research on T1D-OP.