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1.
Polymers (Basel) ; 16(8)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38674941

ABSTRACT

Stereolithography has emerged as a recent method in fabricating complex structures with high accuracy. Components using resin have poorer properties. The current study investigates the improvement in the properties of nano-graphite composites fabricated by the SLA technique. The properties are compared for plain resin and 0.2%, 0.5%, 1%, 3%, and 5% (w/v) of nano-graphite mixed with the UV-curable resin. Various analyses were conducted, including viscosity, UV spectroscopy, moisture content, water absorption, gel content, tensile, bending, hardness testing, and microscopic characterization. The results from the experiments showed a difference in the results of each percentage of the specimen tested, such as the specimen property, which shows that the greater the percentage of nano-graphite added (5%), the opaquer the specimen will appear and less light will be reflected. Viscosity testing shows that the greater the percentage of nano-graphite added to the resin, the greater the viscosity. UV spectroscopy testing produced information about the electronic structure and the structure of molecules, such as their composition, purity, and concentration. Observations from the moisture content analysis found that the moisture content in specimens with higher percentages of nano-graphite affected physical and mechanical properties, leading to easier warping, cracking, decreased strength, etc. Tensile and bending testing shows that the greater the percentage of nano-graphite added, the greater the effect on physical and mechanical properties, including fracture. However, certain tests did not consistently yield significant variations among specimens when different percentages of nano-graphite were added, as particularly evident in chemical resistance testing. This study offers valuable insights into the application of nano-graphite composites fabricated via the SLA method.

2.
Cells ; 13(7)2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38607081

ABSTRACT

Increased activation of ovarian primordial follicles in Erß knockout (ErßKO) rats becomes evident as early as postnatal day 8.5. To identify the ERß-regulated genes that may control ovarian primordial follicle activation, we analyzed the transcriptome profiles of ErßKO rat ovaries collected on postnatal days 4.5, 6.5, and 8.5. Compared to wildtype ovaries, ErßKO ovaries displayed dramatic downregulation of Indian hedgehog (Ihh) expression. IHH-regulated genes, including Hhip, Gli1, and Ptch1, were also downregulated in ErßKO ovaries. This was associated with a downregulation of steroidogenic enzymes Cyp11a1, Cyp19a1, and Hsd17b1. The expression of Ihh remained very low in ErßKO ovaries despite the high levels of Gdf9 and Bmp15, which are known upregulators of Ihh expression in the granulosa cells of activated ovarian follicles. Strikingly, the downregulation of the Ihh gene in ErßKO ovaries began to disappear on postnatal day 16.5 and recovered on postnatal day 21.5. In rat ovaries, the first wave of primordial follicles is rapidly activated after their formation, whereas the second wave of primordial follicles remains dormant in the ovarian cortex and slowly starts activating after postnatal day 12.5. We localized the expression of Ihh mRNA in postnatal day 8.5 wildtype rat ovaries but not in the age-matched ErßKO ovaries. In postnatal day 21.5 ErßKO rat ovaries, we detected Ihh mRNA mainly in the activated follicles in the ovaries' peripheral regions. Our findings indicate that the expression of Ihh in the granulosa cells of the activated first wave of ovarian follicles depends on ERß.


Subject(s)
Estrogen Receptor beta , Hedgehog Proteins , Animals , Female , Rats , Estrogen Receptor beta/genetics , Estrogen Receptor beta/metabolism , Hedgehog Proteins/genetics , Hedgehog Proteins/metabolism , Ovarian Follicle/metabolism , Ovary/metabolism , RNA, Messenger/metabolism
3.
J Clin Gastroenterol ; 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38567896

ABSTRACT

BACKGROUND: Studies evaluating endoscopic full-thickness resection (EFTR) and endoscopic submucosal dissection (ESD) for complex colorectal lesions have shown variable results. We conducted a meta-analysis of the available data. METHODS: Online databases were searched for studies comparing EFTR versus ESD for complex colorectal lesions. The outcomes of interest were resection rates, procedure time (min), and complications. Pooled odds ratios (OR) and standardized mean difference (SMD) along with 95% CI were calculated. RESULTS: A total of 4 studies with 530 patients (n=215 EFTR, n=315 ESD) were included. The mean follow-up duration was 5 months. The mean age of the patients was 68 years and 64% were men. The EFTR and ESD groups had similar rates of en bloc resection (OR: 1.73, 95% CI: 0.60-4.97, P=0.31) and R0 resection (OR: 1.52, 95% CI: 0.55-4.14, P=0.42). The EFTR group had significantly reduced procedure time (SMD -1.87, 95% CI: -3.13 to -0.61, P=0.004), total complications (OR: 0.24, 95% CI: 0.13-0.44, P<0.00001), perforation (OR: 0.12, 95% CI: 0.03-0.39, P=0.0005) and postresection electrocoagulation syndrome (OR: 0.06, 95% CI: 0.01-0.48, P=0.008). Delayed bleeding was similar in the 2 groups (OR: 0.80, 95% CI: 0.30-2.12, P=0.66). Residual/recurrent lesions were significantly higher in the EFTR group (OR: 4.67, 95% CI: 1.39-15.66, P=0.01). DISCUSSION: This meta-analysis of small studies with high heterogeneity showed that EFTR and ESD have comparable resection rates for complex colorectal lesions. EFTR is faster and has fewer complications, but it increases residual or recurrent lesions.

4.
World J Gastrointest Endosc ; 16(1): 37-43, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38313458

ABSTRACT

BACKGROUND: Gastrointestinal (GI) bleeding accounts for over half a million admissions annually and is the most common GI diagnosis requiring hospitalization in the United States. Bipolar electrocoagulation devices are used for the management of gastrointestinal bleeding. There is no data on device-related adverse events for gold probe (GP) and injection gold probe (IGP). AIM: To analyze this using the Food and Drug Administration (FDA's) Manufacturer and User Facility Device Experience (MAUDE) database from 2013 to 2023. METHODS: We examined post-marketing surveillance data on GP and IGP from the FDA MAUDE database to report devicerelated and patient-related adverse events between 2013-2023. The MAUDE database is a publicly available resource providing over 4 million records relating to medical device safety. Statistical analyses were performed using IBM SPSS Statistics V.27.0 (IBM Corp., Armonk, NY, United States). RESULTS: Our search elicited 140 reports for GP and 202 reports for IGP, respectively, during the study period from January 2013 to August 2023. Malfunctions reportedly occurred in 130 cases for GP, and actual patient injury or event occurred in 10 patients. A total of 149 patients (74%) reported with Injection GP events suffered no significant consequences due to the device failure, but 53 patients (26%) were affected by an event. CONCLUSION: GP and IGP are critical in managing gastrointestinal bleeding. This study of the FDA MAUDE database revealed the type, number, and trends of reported device-related adverse events. The endoscopist and support staff must be aware of these device-related events and be equipped to manage them if they occur.

5.
Nat Commun ; 15(1): 1428, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38365898

ABSTRACT

Lead-free, silicon compatible materials showing large electromechanical responses comparable to, or better than conventional relaxor ferroelectrics, are desirable for various nanoelectromechanical devices and applications. Defect-engineered electrostriction has recently been gaining popularity to obtain enhanced electromechanical responses at sub 100 Hz frequencies. Here, we report record values of electrostrictive strain coefficients (M31) at frequencies as large as 5 kHz (1.04×10-14 m2/V2 at 1 kHz, and 3.87×10-15 m2/V2 at 5 kHz) using A-site and oxygen-deficient barium titanate thin-films, epitaxially integrated onto Si. The effect is robust and retained upon cycling upto 6 million times. Our perovskite films are non-ferroelectric, exhibit a different symmetry compared to stoichiometric BaTiO3 and are characterized by twin boundaries and nano polar-like regions. We show that the dielectric relaxation arising from the defect-induced features correlates well with the observed giant electrostriction-like response. These films show large coefficient of thermal expansion (2.36 × 10-5/K), which along with the giant M31 implies a considerable increase in the lattice anharmonicity induced by the defects. Our work provides a crucial step forward towards formulating guidelines to engineer large electromechanical responses even at higher frequencies in lead-free thin films.

6.
Gastrointest Endosc ; 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38382885

ABSTRACT

BACKGROUND AND AIMS: With the global obesity pandemic, clinical scenarios requiring urgent ERCP in patients with gastric bypass surgery are on the rise, and single-session EUS-directed transgastric ERCP (SS-EDGE) can effectively address these technical challenges. The aim of this study was to evaluate and describe the safe and effective use of a through-the-scope endoscopic suturing system for anchoring the lumen-apposing metal stents (LAMSs) during SS-EDGE. METHODS: Six patients with Roux-en-Y gastric bypass (RYGB) underwent SS-EDGE at our center. A through-the-scope endoscopic suturing system was used for anchoring the LAMSs during SS-EDGE. RESULTS: Clinical and technical success was achieved in all 6 patients without any adverse events related to the procedure. No stent migration, pneumoperitoneum, or GI perforation was noted. At the 4-week follow-up, no stent migration was noted, and the through-the-scope suturing system remained anchored. LAMSs along with tacks were removed, and gastric fistulae were successfully closed endoscopically in all patients to prevent weight gain. CONCLUSIONS: Use of through-the-scope endoscopic suturing can be a safe, reliable, and potentially cost-effective novel technique for LAMS fixation to successfully perform SS-EDGE in RYGB patients.

7.
J Reprod Immunol ; 161: 104169, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38016190

ABSTRACT

Testicular macrophages (TM) are critical for the function of the testis by regulating homeostasis and inflammatory responses. However, the mechanisms by which TM fulfil these roles remain elusive. In this study, we explored the impact of two key testicular microenvironmental factors, namely 25-hydroxycholesterol (25HC), an oxysterol related to sex hormones and macrophage colony-stimulating factor (M-CSF), a factor crucial for macrophage survival and differentiation, on the regulation of the TM phenotype. Specifically, we examined their role in controlling the expression of the transcription factor interferon regulatory factor 7 (Irf7), a factor critical for maintaining the alternative macrophage phenotype. To achieve this, we used an in vitro bone marrow-derived macrophage (BMDM) model as a surrogate for TM to investigate the roles of 25HC and M-CSF in regulating the expression of Irf7 during the polarization of murine TM. M-CSF was identified as the main regulator of Irf7 expression, while 25HC production is a consequence of Irf7 activation in BMDM. In turn, 25HC plays a role in a negative feedback loop on the expression levels of Irf7 in BMDM. Using flow cytometry in Irf7-/- mouse testis the CD64loMHChi TM subpopulation was found to be decreased. Together with lower IL-10 protein levels in Irf7-/- TM this indicates a shift towards an M1-like macrophage profile. In summary, our data indicates that M-CSF could act as an inducer of high Irf7 expression levels in the mouse testis. However, the exact role of the high 25HC concentration in the testis in maintaining the local immune milieu still needs further study.


Subject(s)
Macrophage Colony-Stimulating Factor , Testis , Male , Mice , Animals , Macrophage Colony-Stimulating Factor/metabolism , Interferon Regulatory Factor-7 , Macrophages , Transcription Factors
8.
J Biomol Struct Dyn ; : 1-15, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-37997952

ABSTRACT

Type 2 diabetes mellitus is a bipolar metabolic disorder characterized by abnormalities in insulin production from ß-cells and insulin resistance. Thiazolidinediones are potent anti-diabetic agents that act through the modulation of the peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor. However, their full agonistic activity leads to severe side effects by stabilizing Helix12 through strong hydrogen bonding with the TYR473 residue. Partial and selective PPARγ modulators (GW0072, GQ16, VSP-51, MRL-20, MBX-213, INT131) have demonstrated superior results compared to full agonists without causing adverse effects, as reported in existing data. To address this uncertainty and advance therapeutic options, we identified and designed a novel class of compounds (A1-A23) based on a hybrid structure combining phenolic and Thiazolidine-4-one's moieties. Our rational drug design strategy incorporated structural-activity relationship principle, and validated the docking studies through calculated the root mean square deviation. Additionally, we conducted molecular docking, binding energy, molecular dynamics simulations, and post-molecular dynamics calculations to evaluate the dynamics behavior between the ligands and protein. The selected ligands demonstrated highly favorable docking scores and binding energies, comparable to the co-crystal (rosiglitazone) such as A12 (-13.9 kcal/mol and -86.2 kcal/mol), A1 (-11.1 kcal/mol and -79.5 kcal/mol), A13 (-11.3 kcal/mol and -91.4 kcal/mol), and the co-crystal itself (-9.8 kcal/mol and -76 kcal/mol), respectively. Finally, the MD revealed that, the selected ligands were equally contributed for stabilization of Helix12 and ß-sheets. It was concluded, the designed ligands (A12, A1, and A13) exhibited weaker hydrogen-bond interactions with specific residue TYR473 which partially modulated the PPARγ protein.Communicated by Ramaswamy H. Sarma.

9.
Mol Cell Proteomics ; 22(12): 100678, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37952696

ABSTRACT

Microglia are resident immune cells of the brain that play important roles in mediating inflammatory responses in several neurological diseases via direct and indirect mechanisms. One indirect mechanism may involve extracellular vesicle (EV) release, so that the molecular cargo transported by microglia-derived EVs can have functional effects by facilitating intercellular communication. The molecular composition of microglia-derived EVs, and how microglial activation states impact EV composition and EV-mediated effects in neuroinflammation, remain poorly understood. We hypothesize that microglia-derived EVs have unique molecular profiles that are determined by microglial activation state. Using size-exclusion chromatography to purify EVs from BV2 microglia, combined with proteomic (label-free quantitative mass spectrometry or LFQ-MS) and transcriptomic (mRNA and noncoding RNA seq) methods, we obtained comprehensive molecular profiles of microglia-derived EVs. LFQ-MS identified several classic EV proteins (tetraspanins, ESCRT machinery, and heat shock proteins), in addition to over 200 proteins not previously reported in the literature. Unique mRNA and microRNA signatures of microglia-derived EVs were also identified. After treating BV2 microglia with lipopolysaccharide (LPS), interleukin-10, or transforming growth factor beta, to mimic pro-inflammatory, anti-inflammatory, or homeostatic states, respectively, LFQ-MS and RNA seq revealed novel state-specific proteomic and transcriptomic signatures of microglia-derived EVs. Particularly, LPS treatment had the most profound impact on proteomic and transcriptomic compositions of microglia-derived EVs. Furthermore, we found that EVs derived from LPS-activated microglia were able to induce pro-inflammatory transcriptomic changes in resting responder microglia, confirming the ability of microglia-derived EVs to relay functionally relevant inflammatory signals. These comprehensive microglia-EV molecular datasets represent important resources for the neuroscience and omics communities and provide novel insights into the role of microglia-derived EVs in neuroinflammation.


Subject(s)
Extracellular Vesicles , Microglia , Humans , Microglia/metabolism , Proteomics/methods , Neuroinflammatory Diseases , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Gene Expression Profiling , Extracellular Vesicles/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism
10.
J Mater Sci Mater Med ; 34(12): 62, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37982917

ABSTRACT

3D printing technology is an emerging method that gained extensive attention from researchers worldwide, especially in the health and medical fields. Biopolymers are an emerging class of materials offering excellent properties and flexibility for additive manufacturing. Biopolymers are widely used in biomedical applications in biosensing, immunotherapy, drug delivery, tissue engineering and regeneration, implants, and medical devices. Various biodegradable and non-biodegradable polymeric materials are considered as bio-ink for 3d printing. Here, we offer an extensive literature review on the current applications of synthetic biopolymers in the field of 3D printing. A trend in the publication of biopolymers in the last 10 years are focused on the review by analyzing more than 100 publications. Their application and classification based on biodegradability are discussed. The various studies, along with their practical applications, are elaborated in the subsequent sections for polyethylene, polypropylene, polycaprolactone, polylactide, etc. for biomedical applications. The disadvantages of various biopolymers are discussed, and future perspectives like combating biocompatibility problems using 3D printed biomaterials to build compatible prosthetics are also discussed and the potential application of using resin with the combination of biopolymers to build customized implants, personalized drug delivery systems and organ on a chip technologies are expected to open a new set of chances for the development of healthcare and regenerative medicine in the future.


Subject(s)
Artificial Limbs , Printing, Three-Dimensional , Biopolymers , Polyethylene , Polymers , Polypropylenes/chemistry
11.
J Trace Elem Med Biol ; 80: 127308, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37801785

ABSTRACT

Spatial and temporal variations have been found in the levels of arsenic (As) throughout the groundwater of the Ghaghara basin. Fifteen out of twenty-five districts in this basin are reported to be affected by As, where the levels of As in groundwater and soil exceed the permissible limits set by the WHO (10 µgl-1) and FAO (20 mgkg-1) respectively. These districts include a total of four municipalities in Nepal and eighty-six blocks in India, all of which have varying degrees of As contamination. Approximately 17 million people are at risk of As poisoning, with more than two orders of magnitude higher potential lifetime incremental cancer risk, constituting over 153 thousand potential additional cases of cancer due to As-contaminated drinking water. Out of the 90 As-contaminated blocks in the Ghaghara basin, 4 blocks have about 7-fold higher potential risk of developing cancer, 49 blocks have 8-37-fold higher risk, and 37 blocks have up to 375-fold higher risk compared to the upper limit of the USEPA acceptable range, which is 1 × 10-6-1 × 10-4. High accumulation of As has been reported in the nails, hair, and urine of local inhabitants, with higher levels observed in females than males. The toxicity of As is manifested in terms of a higher occurrence of various diseases. Reproductive endpoints, such as increased incidences of preterm birth, spontaneous abortion, stillbirth, low-birth weight, and neonatal death, have also been reported in the basin. The level of As in tube wells has been found to be negatively correlated with the depth (r = -0.906), and tube wells with high levels of As (>150 µgl-1) are generally located within close proximity (<10 km) to abandoned or present meander channels in the floodplain areas of the Ghaghara river. In addition to As contamination, the water quality index (WQI) in the Ghaghara basin is poor according to the BIS standards for drinking water. Groundwater in six out of fifteen districts is unsuitable for drinking purposes, with a WQI exceeding 100. The levels of As in agricultural soil in many villages of Ballia, Bahraich, and Lakhimpur Kheri districts have exceeded the FAO limit. Water from deep tube wells has been found to be relatively safe in terms of As content, and thus can be recommended for drinking purposes. However, the use of surface water needs to be encouraged for irrigation purposes in order to preserve soil health and reduce As contamination in the food chain, thereby minimizing the risk of cancer.


Subject(s)
Arsenic , Drinking Water , Groundwater , Neoplasms , Premature Birth , Water Pollutants, Chemical , Infant, Newborn , Male , Pregnancy , Female , Humans , Arsenic/analysis , Water Pollutants, Chemical/analysis , Neoplasms/epidemiology , Soil , India/epidemiology , Environmental Monitoring
12.
Phys Chem Chem Phys ; 25(37): 25639-25653, 2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37721171

ABSTRACT

In the present study, synchrotron-based X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS) and X-ray excited optical luminescence (XEOL) have been used to investigate the induced defect states in metal oxide nanomaterials. Specifically, two synthesis approaches have been followed to develop unique nano-sized peanut-shaped (N-ZnO) nanostructures and micron-sized hexagonal rods (M-ZnO). XANES analysis at the Zn K-edge revealed the presence of defect states with a divalent oxidation state of zinc (Zn2+) in a tetrahedral structure. Furthermore, XAS measurements performed at the Zn L3,2-edge and O K-edge confirm higher oxygen-related defects in M-ZnO, while N-ZnO appeared to have a higher concentration of surface defects due to size confinement. Moreover, the in-line XEOL and time dependent-XEOL measurements exposed the radiative excitonic recombination phenomena occurring in the band-tailing region as a function of absorption length, X-ray energy excitation, and time. Based on the chronology developed in the defect state improvement, a possible energy band diagram is proposed to accurately locate the defect states in the two systems. Furthermore, the increased absorption intensity at the Zn L3,2-edge and the O K-edge under the UV lamp suggests delayed recombination of electrons and holes, highlighting their potential use as photo catalysts. The photocatalytic activity degrading the rhodamine B dye established M-ZnO as a superior catalyst with a rapid degradation rate and significant mineralization. Overall, this work provides valuable insights into ZnO defect states and provides a foundation for efficient advanced materials for environmental or other optoelectronic applications.

13.
Eur J Gastroenterol Hepatol ; 35(10): 1192-1196, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37577797

ABSTRACT

BACKGROUND: Alcohol-associated liver disease is increasing among females with an earlier onset and more severe disease at lower levels of exposure. However, there is paucity of literature regarding sex differences related to alcoholic hepatitis. METHODS: Hospitalized patients with alcoholic hepatitis were selected from the US Nationwide readmissions database 2019. In this cohort, we evaluated sex differences in baseline comorbidities, alcoholic hepatitis related complications and mortality. A subset of patients with alcoholic hepatitis who were hospitalized between January and June 2019 were identified to study sex differences in 6 month readmission rate, mortality during readmission, and composite of mortality during index hospitalization or readmission. RESULTS: Among 112 790 patients with alcoholic hepatitis, 33.3% were female. Female patients were younger [48 (38-57) vs. 49 (39-58) years; both P  < 0.001] but had higher rates of important medical and mental-health related comorbidities. Compared with males, females had higher rates of hepatic encephalopathy (11.5% vs. 10.1; P  < 0.001), ascites (27.9% vs. 22.5%; P  < 0.001), portal hypertension (18.5% vs. 16.4%; P  < 0.001), cirrhosis (37.3% vs. 31.9%; P  < 0.001), weight loss (19.0% vs. 14.5%; P  < 0.001), hepatorenal syndrome (4.4% vs. 3.8%; P  < 0.001), spontaneous bacterial peritonitis (1.9% vs. 1.7%; P  = 0.026), sepsis (11.1% vs. 9.5%; P  < 0.001), and blood transfusion (12.9% vs. 8.7%; P  < 0.001). Females had a similar in-hospital mortality rate (4.3%) compared to males (4.1%; P  = 0.202; adjusted odds ratio (OR) 1.02, 95% CI (cardiac index) 0.89-1.15; P  = 0.994). In the subset of patients ( N  = 58 688), females had a higher 6-month readmission rate (48.9% vs. 44.9%; adjusted OR 1.12 (1.06-1.18); P  < 0.001), mortality during readmission (4.4% vs. 3.2%; OR 1.23 (1.08-1.40); P  < 0.01), and composite of mortality during index hospitalization or readmission (8.7% vs. 7.2%; OR 1.15 (1.04-1.27); P  < 0.01). CONCLUSION: Compared to their male counterparts, females with alcoholic hepatitis were generally younger but had higher rates of comorbidities, alcoholic hepatitis related complications, rehospitalizations and associated mortality. The greater risks of alcohol-associated liver dysfunction in females indicate the need for more aggressive management.


Subject(s)
Hepatitis, Alcoholic , Humans , Male , Female , Hepatitis, Alcoholic/diagnosis , Hepatitis, Alcoholic/epidemiology , Hepatitis, Alcoholic/therapy , Sex Characteristics , Retrospective Studies , Hospitalization , Liver Cirrhosis
14.
bioRxiv ; 2023 Jul 29.
Article in English | MEDLINE | ID: mdl-37546899

ABSTRACT

Microglia are resident immune cells of the brain that play important roles in mediating inflammatory responses in several neurological diseases via direct and indirect mechanisms. One indirect mechanism may involve extracellular vesicle (EV) release, so that the molecular cargo transported by microglia-derived EVs can have functional effects by facilitating intercellular communication. The molecular composition of microglia-derived EVs, and how microglial activation states impacts EV composition and EV-mediated effects in neuroinflammation, remain poorly understood. We hypothesize that microglia-derived EVs have unique molecular profiles that are determined by microglial activation state. Using size-exclusion chromatography to purify EVs from BV2 microglia, combined with proteomic (label-free quantitative mass spectrometry or LFQ-MS) and transcriptomic (mRNA and non-coding RNA seq) methods, we obtained comprehensive molecular profiles of microglia-derived EVs. LFQ-MS identified several classic EV proteins (tetraspanins, ESCRT machinery, and heat shock proteins), in addition to over 200 proteins not previously reported in the literature. Unique mRNA and microRNA signatures of microglia-derived EVs were also identified. After treating BV2 microglia with lipopolysaccharide (LPS), interleukin-10, or transforming growth factor beta, to mimic pro-inflammatory, anti-inflammatory, or homeostatic states, respectively, LFQ-MS and RNA seq revealed novel state-specific proteomic and transcriptomic signatures of microglia-derived EVs. Particularly, LPS treatment had the most profound impact on proteomic and transcriptomic compositions of microglia-derived EVs. Furthermore, we found that EVs derived from LPS-activated microglia were able to induce pro-inflammatory transcriptomic changes in resting responder microglia, confirming the ability of microglia-derived EVs to relay functionally-relevant inflammatory signals. These comprehensive microglia-EV molecular datasets represent important resources for the neuroscience and glial communities, and provide novel insights into the role of microglia-derived EVs in neuroinflammation.

15.
Polymers (Basel) ; 15(5)2023 Feb 24.
Article in English | MEDLINE | ID: mdl-36904378

ABSTRACT

The current study investigates the effect of a hybrid L-profile aluminium/glass-fiber-reinforced polymer stacking sequence under axial and lateral compression loads. Four stacking sequences are studied: aluminium (A)-glass-fiber (GF)-AGF, GFA, GFAGF, and AGFA. In the axial compression test, the aluminium/GFRP hybrid tends to crush in a more progressive and stable failure than the net aluminium and net GFRP specimens, with a relatively more stable load-carrying capacity throughout the experimental tests. The AGF stacking sequence was second, with an energy absorption of 145.31 kJ, following AGFA at 157.19 kJ. The load-carrying capacity of AGFA was the highest, with an average peak crushing force of 24.59 kN. The second-highest peak crushing force, 14.94 kN, was achieved by GFAGF. The highest amount of energy absorption, 157.19 J, was achieved by the AGFA specimen. The lateral compression test showed a significant increase in load-carrying and energy absorption capacity in the aluminium/GFRP hybrid specimens compared to the net GFRP specimens. AGF had the highest energy absorption with 10.41 J, followed by AGFA with 9.49 J. AGF also had the highest peak crushing force with 2.98 kN, followed by AGFA with 2.16 kN. The most crashworthy stacking sequence among the four variations tested in this experimental research was the AGF stacking sequence because of its great load-carrying capacity, energy absorption, and specific energy absorption in axial and lateral loading. The study provides greater insight into the failure of hybrid composite laminates under lateral and axial compression.

16.
Cells ; 12(3)2023 01 18.
Article in English | MEDLINE | ID: mdl-36766700

ABSTRACT

Three distinct hedgehog (HH) molecules, (sonic, desert, and indian), two HH receptors (PTCH1 and PTCH2), a membrane bound activator (SMO), and downstream three transcription factors (GLI1, GLI2, and GLI3) are the major components of the HH signaling. These signaling molecules were initially identified in Drosophila melanogaster. Later, it has been found that the HH system is highly conserved across species and essential for organogenesis. HH signaling pathways play key roles in the development of the brain, face, skeleton, musculature, lungs, and gastrointestinal tract. While the sonic HH (SHH) pathway plays a major role in the development of the central nervous system, the desert HH (DHH) regulates the development of the gonads, and the indian HH (IHH) acts on the development of bones and joints. There are also overlapping roles among the HH molecules. In addition to the developmental role of HH signaling in embryonic life, the pathways possess vital physiological roles in testes and ovaries during adult life. Disruption of DHH and/or IHH signaling results in ineffective gonadal steroidogenesis and gametogenesis. While DHH regulates the male gonadal functions, ovarian functions are regulated by both DHH and IHH. This review article focuses on the roles of HH signaling in gonadal development and reproductive functions with an emphasis on ovarian functions. We have acknowledged the original research work that initially reported the findings and discussed the subsequent studies that have further analyzed the role of HH signaling in testes and ovaries.


Subject(s)
Drosophila melanogaster , Hedgehog Proteins , Female , Animals , Male , Hedgehog Proteins/metabolism , Drosophila melanogaster/metabolism , Signal Transduction/physiology , Ovary/metabolism , Transcription Factors/metabolism
17.
Crit Rev Biotechnol ; 43(4): 575-593, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35435095

ABSTRACT

Bounteous modern and innovative biotechnological tools have resulted in progressive development in the barley breeding program. Doubled haploids developed (homozygous lines) in a single generation is significant. Since the first discovery of haploid plants in 1920 and, in particular, after discovering in vitro androgenesis in 1964 by Guha and Maheshwari, the doubled haploidy techniques have been progressively developed and constantly improved. It has shortened the cultivar development time and has been extensively used in: genetic studies, gene mapping, marker/trait association, and QTL studies. In barley, the haploid occurrence developed gradually from being a sporadic and random process (spontaneous) to haploid development by in vivo method of modified pollination or by in vitro culture of immature male or female gametophytes. Although significant improvement in DH induction protocols has been made, challenges still exist for improvement in areas such as: low efficiency, albinism, genotypic specificity etc. Here, the paper focuses on: haploidization via different in vitro, in vivo techniques, the recent advances technologies like centromere-mediated haploidization, hap induction gene, and Doubled haploid CRISPR. The au-courant work of different researchers in barley using these technologies is reviewed. Studies on different factors affecting haploid induction and work on genome doubling of barley haploids to produce DH lines via spontaneous and induced technologies has also been highlighted.


Subject(s)
Hordeum , Haploidy , Hordeum/genetics , Plants , Phenotype , Plant Breeding
18.
Harm Reduct J ; 19(1): 5, 2022 01 16.
Article in English | MEDLINE | ID: mdl-35034649

ABSTRACT

BACKGROUND: The opioid epidemic is a rapidly growing public health concern in the USA, as the number of overdose deaths continues to increase each year. One strategy for combating the rising number of overdoses is through opioid overdose prevention programs (OOPPs). OBJECTIVE: To evaluate the effectiveness of an innovative OOPP, with changes in knowledge and attitudes serving as the primary outcome measures. METHODS: The OOPP was developed by a group of medical students under guidance from faculty advisors. Training sessions focused on understanding stigmatizing factors of opioid use disorder (OUD), as well as protocols for opioid overdose reversal through naloxone administration. Pre- and post-surveys were partially adapted from the opioid overdose attitudes and knowledge scales and administered to all participants. Paired t-tests were conducted to assess differences between pre- and post-surveys. RESULTS: A total of 440 individuals participated in the training; 381 completed all or the majority of the survey. Participants came from a diverse set of backgrounds, ages, and experiences. All three knowledge questions showed significant improvements. For attitude questions, significant improvements were found in all three questions evaluating confidence, two of three questions assessing attitudes towards overdose reversal, and four of five questions evaluating stigma and attitudes towards individuals with OUD. CONCLUSIONS: Our innovative OOPP was effective not only in increasing knowledge but also in improving attitudes towards overdose reversal and reducing stigma towards individuals with OUD. Given the strong improvements in attitudes towards those with OUD, efforts should be made to incorporate the unique focus on biopsychosocial and sociohistorical components into future OOPPs.


Subject(s)
Drug Overdose , Opiate Overdose , Opioid-Related Disorders , Analgesics, Opioid/therapeutic use , Drug Overdose/drug therapy , Drug Overdose/prevention & control , Health Knowledge, Attitudes, Practice , Humans , Naloxone/therapeutic use , Narcotic Antagonists/therapeutic use , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/prevention & control
19.
Npj Ment Health Res ; 1(1): 3, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-38609492

ABSTRACT

Suicide is a growing public health concern in the United States. A detailed understanding and prediction of suicide patterns can significantly boost targeted suicide control and prevention efforts. In this article we look at the suicide trends and geographical distribution of suicides and then develop a machine learning based US county-level suicide prediction model, using publicly available data for the 10-year period from 2010-2019. Analysis of the trends and geographical distribution of suicides revealed that nearly 25% of the total counties experienced at least a 10% increase in suicides from 2010 to 2019, with about 12% of total counties exhibiting an increase of at least 50%. An eXtreme Gradient Boosting (XGBoost) based machine learning model was used with 17 unique features for each of the 3140 counties in the US to predict suicides with an R2 value of 0.98. Using the SHapley Additive exPlanations (SHAP) values, the importance of all the 17 features used in the prediction model training set were identified. County level features, namely Total Population, % African American Population, % White Population, Median Age and % Female Population were found to be the top 5 important features that significantly affected prediction results. The top five important features based on SHAP values were then used to create a Suicide Vulnerability Index (SVI) for US Counties. This newly developed SVI has the potential to detect US counties vulnerable to high suicide rates and can aid targeted suicide control and prevention efforts, thereby making it a valuable tool in an informed decision-making process.

20.
Proc (Bayl Univ Med Cent) ; 34(6): 696-697, 2021.
Article in English | MEDLINE | ID: mdl-34732991

ABSTRACT

Syphilis is a multisystem disease caused by the spirochete Treponema pallidum. Among various organs affected, liver involvement is seen infrequently and can be missed. Here we present a case of hepatitis due to secondary syphilis that completely resolved with penicillin G therapy.

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