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1.
Mol Cell Proteomics ; 22(10): 100637, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37648026

RESUMO

cAMP response element-binding protein (CREB) regulated transcriptional coactivator 2 (CRTC2) is a critical transcription factor that maintains glucose homeostasis by activating CREB. Energy homeostasis is maintained through multiple pathways; therefore, CRTC2 may interact with other transcription factors, particularly under metabolic stress. CRTC2 liver-specific KO mice were created, and the global proteome, phosphoproteome, and acetylome from liver tissue under high-fat diet conditions were analyzed using liquid chromatography-tandem mass spectrometry and bioinformatics analysis. Differentially regulated proteins (DRPs) were enriched in metabolic pathways, which were subsequently corroborated through animal experiments. The consensus DRPs from these datasets were used as seed proteins to generate a protein-protein interaction network using STRING, and GeneMANIA identified fatty acid synthase as a mutually relevant protein. In an additional local-protein-protein interaction analysis of CRTC2 and fatty acid synthase with DRPs, sterol regulatory element binding transcription factor 1 (SREBF1) was the common mediator. CRTC2-CREB and SREBF1 are transcription factors, and DNA-binding motif analysis showed that multiple CRTC2-CREB-regulated genes possess SREBF1-binding motifs. This indicates the possible induction by the CRTC2-SREBF1 complex, which is validated through luciferase assay. Therefore, the CRTC2-SREBF1 complex potentially modulates the transcription of multiple proteins that fine-tune cellular metabolism under metabolic stress.

2.
BMC Genomics ; 25(1): 597, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877411

RESUMO

Chrozophora sabulosa Kar. & Kir. is a biennial herbaceous plant that belongs to the Euphorbiaceae family and has medicinal properties. This research aimed to identify the genetic characteristics and phylogenetic position of the Chrozophora genus within the Euphorbiaceae family. The evolutionary position of the Chrozophora genus was previously unknown due to insufficient research. Therefore, to determine the evolutionary link between C. sabulosa and other related species, we conducted a study using the NGS Illumina platform to sequence the C. sabulosa chloroplast (cp.) genome. The study results showed that the genome was 156,488 bp in length. It had a quadripartite structure consisting of two inverted repeats (IRb and IRa) of 24,649-bp, separated by an 87,696-bp LSC region and a 19,494-bp SSC region. The CP genome contained 113 unique genes, including four rRNA genes, 30 tRNA genes, and 79 CDS genes. In the second copy of the inverted repeat, there were 18 duplicated genes. The C. sabulosa lacks the petD, petB, rpl2, and rps16 intron. The analysis of simple sequence repeats (SSRs) revealed 93 SSR loci of 22 types and 78 oligonucleotide repeats of four kinds. The phylogenetic investigation showed that the Chrozophora genus evolved paraphyletically from other members of the Euphorbiaceae family. To support the phylogenetic findings, we selected species from the Euphorbiaceae and Phyllanthaceae families to compare with C. sabulosa for Ks and Ka substitution rates, InDels investigation, IR contraction and expansion, and SNPs analysis. The results of these comparative studies align with the phylogenetic findings. We identified six highly polymorphic regions shared by both families, which could be used as molecular identifiers for the Chrozophora genus (rpl33-rps18, rps18-rpl20, rps15-ycf1, ndhG-ndhI, psaI-ycf4, petA-psbJ). The cp. genome sequence of C. sabulosa reveals the evolution of plastid sequences in Chrozophora species. This is the first time the cp. genome of a Chrozophora genus has been sequenced, serving as a foundation for future sequencing of other species within the Chrozophoreae tribe and facilitating in-depth taxonomic research. The results of this research will also aid in identifying new Chrozophora species.


Assuntos
Evolução Molecular , Genoma de Cloroplastos , Filogenia
3.
Biochem Cell Biol ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306631

RESUMO

Currently used lung disease screening tools are expensive in terms of money and time. Therefore, chest radiograph images (CRIs) are employed for prompt and accurate COVID-19 identification. Recently, many researchers have applied Deep learning (DL) based models to detect COVID-19 automatically. However, their model could have been more computationally expensive and less robust, i.e., its performance degrades when evaluated on other datasets. This study proposes a trustworthy, robust, and lightweight network (ChestCovidNet) that can detect COVID-19 by examining various CRIs datasets. The ChestCovidNet model has only 11 learned layers, eight convolutional (Conv) layers, and three fully connected (FC) layers. The framework employs both the Conv and group Conv layers, Leaky Relu activation function, shufflenet unit, Conv kernels of 3×3 and 1×1 to extract features at different scales, and two normalization procedures that are cross-channel normalization and batch normalization. We used 9013 CRIs for training whereas 3863 CRIs for testing the proposed ChestCovidNet approach. Furthermore, we compared the classification results of the proposed framework with hybrid methods in which we employed DL frameworks for feature extraction and support vector machines (SVM) for classification. The study's findings demonstrated that the embedded low-power ChestCovidNet model worked well and achieved a classification accuracy of 98.12% and recall, F1-score, and precision of 95.75%.

4.
J Virol ; 97(6): e0038223, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37289075

RESUMO

Palmitoylation of viral proteins is crucial for host-virus interactions. In this study, we examined the palmitoylation of Japanese encephalitis virus (JEV) nonstructural protein 2A (NS2A) and observed that NS2A was palmitoylated at the C221 residue of NS2A. Blocking NS2A palmitoylation by introducing a cysteine-to-serine mutation at C221 (NS2A/C221S) impaired JEV replication in vitro and attenuated the virulence of JEV in mice. NS2A/C221S mutation had no effect on NS2A oligomerization and membrane-associated activities, but reduced protein stability and accelerated its degradation through the ubiquitin-proteasome pathway. These observations suggest that NS2A palmitoylation at C221 played a role in its protein stability, thereby contributing to JEV replication efficiency and virulence. Interestingly, the C221 residue undergoing palmitoylation was located at the C-terminal tail (amino acids 195 to 227) and is removed from the full-length NS2A following an internal cleavage processed by viral and/or host proteases during JEV infection. IMPORTANCE An internal cleavage site is present at the C terminus of JEV NS2A. Following occurrence of the internal cleavage, the C-terminal tail (amino acids 195 to 227) is removed from the full-length NS2A. Therefore, it was interesting to discover whether the C-terminal tail contributed to JEV infection. During analysis of viral palmitoylated protein, we observed that NS2A was palmitoylated at the C221 residue located at the C-terminal tail. Blocking NS2A palmitoylation by introducing a cysteine-to-serine mutation at C221 (NS2A/C221S) impaired JEV replication in vitro and attenuated JEV virulence in mice, suggesting that NS2A palmitoylation at C221 contributed to JEV replication and virulence. Based on these findings, we could infer that the C-terminal tail might play a role in the maintenance of JEV replication efficiency and virulence despite its removal from the full-length NS2A at a certain stage of JEV infection.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Proteínas não Estruturais Virais , Replicação Viral , Animais , Camundongos , Linhagem Celular , Cisteína/metabolismo , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Lipoilação , Serina/metabolismo , Proteínas não Estruturais Virais/metabolismo , Virulência
5.
Strahlenther Onkol ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918259

RESUMO

INTRODUCTION: Risk factors for developing osteoradionecrosis (ORN) are well known, but less is known about factors influencing the interval between radiotherapy and the onset of ORN. Also, it is unknown whether there is any specific period post-radiotherapy with a reduced probability of ORN when irradiated teeth require extraction. PURPOSE: The primary aim of this study was to identify factors influencing the interval in developing ORN in the following subgroups of patients: (1) patients who spontaneously developed ORN, (2) surgical-intervention-related ORN with a particular focus on patients after mandibulectomy. The secondary aim was to attempt to identify a possible time for safer dental intervention after primary treatment. MATERIALS AND METHODS: The authors retrospectively analysed 1608 head and neck cancer (HNC) patients treated in a single centre. Time intervals were measured from the end of radiotherapy to the development of ORN and further analysed in the subgroups listed above. RESULTS: In all, 141 patients (8.8%) developed intra-oral ORN. Median time from radiotherapy to ORN development in the whole cohort was 9 months. Median interval for spontaneous ORN was 8 months, 6.5 months for intervention-related ORN, and 15 months for patients post-mandibulectomy. In patients who required dental extraction preradiotherapy, median interval of ORN onset was 5 months. CONCLUSION: In our study, a slightly higher proportion of patients with intervention developed ORN earlier in comparison with spontaneous ORN. The period from 12-18 months after radiotherapy was identified as having the highest probability of developing ORN in patients after mandibulectomy. A time for safer dental intervention after primary treatment was not identified.

6.
BMC Vet Res ; 20(1): 39, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297263

RESUMO

BACKGROUND: Brucellosis is a zoonotic disease caused by a bacterial pathogen belonging to the genus Brucella. It is one of the most frequent bacterial zoonoses globally but unfortunately, it is still considered as a neglected disease in the developing world. Keeping in view, this study was conducted to determine the prevalence and risk determinants of brucellosis in large ruminants of peri-urban and rural areas of district Multan-Pakistan. For this purpose, blood samples (n = 490) were collected from the cattle (n = 245) and buffalo (n = 245) population of the study area and subjected to preliminary screening of brucellosis using local and imported RBPT reagents. All the samples were further analyzed using commercially available multi-specie indirect ELISA kit followed by their confirmation by PCR using genus and species-specific primers. Data obtained from lab analysis and questionnaires were subjected to statistical analysis for Pearson Chi-square, Odds Ratio and Confidence intervals (95%). RESULTS: The results showed that the maximum seropositivity was recorded with local RBPT reagent (VRI, Pakistan; 12.45%; 95%CI = 9.72-15.65%) followed by RBPT-IDEXX (12.24%; 95%CI = 9.52-15.45%) and RBPT-ID.vet (11.84%; 95%CI = 9.18-14.95%) however statistical difference was non-significant (P = 0.956). The ELISA results showed an overall seroprevalence rate of 11.22% (95%CI = 8.59-14.33%) with comparatively higher rate in cattle (12.65%; 95%CI = 8.82-17.44%) as compared to buffaloes (9.80%; 95%CI = 6.49-14.15%). The PCR analysis confirmed the presence of genus Brucella in all seropositive samples whereas frequency of B. abortus and B. melitensis in seropositive samples was 80% and 20%, respectively. The co-existence of both species was also observed in 5.45% samples. The statistical analysis showed a significant association of bovine brucellosis with herd size, breed, reproductive disorders, mode of insemination, educational status and farmers' awareness about brucellosis (P < 0.05). Conversely, locality, age, weight, gender, pregnancy status, parity and puberty status had no associations with brucellosis (P > 0.05). CONCLUSION: In conclusion, brucellosis is prevalent in large ruminants of district Multan, Pakistan. It is suggested to devise and implement stringent policies for the effective control and prevention of brucellosis in the region. Further, the current situation also warrants the need to strengthen interdisciplinary coordination among veterinarians and physicians in one health perspective to ensure and strengthen the human and animal health care systems in the region.


Assuntos
Bison , Brucella , Brucelose Bovina , Brucelose , Doenças dos Bovinos , Humanos , Feminino , Bovinos , Animais , Gravidez , Paquistão/epidemiologia , Estudos Soroepidemiológicos , Brucelose/veterinária , Zoonoses , Búfalos , Fatores de Risco , Brucelose Bovina/epidemiologia , Doenças dos Bovinos/epidemiologia
7.
Skin Res Technol ; 30(8): e13878, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39081158

RESUMO

BACKGROUND: Skin diseases are severe diseases. Identification of these severe diseases depends upon the abstraction of atypical skin regions. The segmentation of these skin diseases is essential to rheumatologists in risk impost and for valuable and vital decision-making. Skin lesion segmentation from images is a crucial step toward achieving this goal-timely exposure of malignancy in psoriasis expressively intensifies the persistence ratio. Defies occur when people presume skin diseases they have without accurately and precisely incepted. However, analyzing malignancy at runtime is a big challenge due to the truncated distinction of the visual similarity between malignance and non-malignance lesions. However, images' different shapes, contrast, and vibrations make skin lesion segmentation challenging. Recently, various researchers have explored the applicability of deep learning models to skin lesion segmentation. MATERIALS AND METHODS: This paper introduces a skin lesions segmentation model that integrates two intelligent methodologies: Bayesian inference and edge intelligence. In the segmentation model, we deal with edge intelligence to utilize the texture features for the segmentation of skin lesions. In contrast, Bayesian inference enhances skin lesion segmentation's accuracy and efficiency. RESULTS: We analyze our work along several dimensions, including input data (datasets, preprocessing, and synthetic data generation), model design (architecture, modules), and evaluation aspects (data annotation requirements and segmentation performance). We discuss these dimensions from seminal works and a systematic viewpoint and examine how these dimensions have influenced current trends. CONCLUSION: We summarize our work with previously used techniques in a comprehensive table to facilitate comparisons. Our experimental results show that Bayesian-Edge networks can boost the diagnostic performance of skin lesions by up to 87.80% without incurring additional parameters of heavy computation.


Assuntos
Teorema de Bayes , Dermatopatias , Humanos , Dermatopatias/diagnóstico por imagem , Dermatopatias/patologia , Internet das Coisas , Aprendizado Profundo , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Pele/diagnóstico por imagem , Pele/patologia , Dermoscopia/métodos , Algoritmos
8.
Regul Toxicol Pharmacol ; 146: 105536, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056705

RESUMO

This study aimed to isolate and characterize moringa leaf protein (MLP) via HPLC and evaluate its consumption's effects through rat model. Four groups of Albino Wistar rats (n = 25 each) along with a control group (n = 25) were acclimatized. The isolated MLP was added to the basal diet (casein; control) in various percentages (25, 50, 75, 100%) for a 21-day experimental period. On three intervals (1st, 11th, 21st days), blood samples were collected and subjected for hematological and biochemical examination (Renal Function Test (RFT), Liver Function Test (LFT)). MLP contained a variety of essential and non-essential amino acids in substantial amounts. The Protein Efficiency Ratio (PER) of 50% MLP-treated group was the highest (1.72) among MLP treatments. Increases in feed intake and weight were observed in treated rats compared to the control. The hematological profile of the rats revealed increases in Hemoglobin (Hb) (7.9-14.0%), White Blood Cell (WBC) (35.9-51.5%), Red Blood Cell (RBC) (17.1-22.2%), Hematocrit (HCT) (13.1-22.9%), and platelets levels (36.5-40.6%) from day 1. Protein isolates decreased liver parameters but resulted in non-significant changes in liver and kidney functions in rats. Further investigation is needed to determine the safe daily intake of MLP.


Assuntos
Moringa oleifera , Proteínas de Plantas , Ratos , Animais , Moringa oleifera/química , Proteínas de Carne/análise , Extratos Vegetais/farmacologia , Ratos Wistar , Carne , Folhas de Planta/química
9.
J Oncol Pharm Pract ; : 10781552241245332, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38576329

RESUMO

INTRODUCTION: Acute pancreatitis (AP) following drug-induced hypertriglyceridemia is a rare clinical phenomenon. Immune checkpoint inhibitors have revolutionized treatment for a variety of solid organ and hematological malignancies. Pembrolizumab is a programmed cell death receptor-1 (PD-1) inhibitor that has shown promising responses in many advanced cancers. However, a constellation of immune-related adverse events has also been described. There are reports of pembrolizumab-induced hypertriglyceridemia, but AP as a result of this side effect remains an exceedingly rare clinical sequela. CASE REPORT: We delineate a case of a patient with stage IVB non-small-cell lung cancer who developed progressive abdominal pain and nausea following administration of pembrolizumab for four months. Laboratory studies revealed increased serum lipase and triglyceride levels at 12,562 IU/L and 16,901 mg/dL, respectively. The diagnosis of AP was made based on the revised Atlanta classification criteria. After ruling out alternative causes, pembrolizumab-induced hypertriglyceridemia was considered the likely etiology of AP. MANAGEMENT AND OUTCOME: The patient was transferred to the medical intensive care unit for close monitoring. Treatment was initiated with intravenous fluids, pain medications, and an insulin infusion. However, her hypertriglyceridemia levels remained persistently elevated, necessitating therapeutic apheresis. She recovered well with no complications after triglyceride apheresis. DISCUSSION: AP following pembrolizumab-associated hypertriglyceridemia remains a rare clinicopathologic entity. Given the widespread clinical use of immune checkpoint inhibitors, knowledge of such rare adverse events is crucial. Evaluation of serum triglyceride levels before and after initiating pembrolizumab therapy may be mandated, especially in patients with metabolic comorbidities.

10.
Can J Infect Dis Med Microbiol ; 2024: 8898827, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384430

RESUMO

Brucellosis is a widespread zoonotic disease of veterinary and public health importance with considerably higher prevalence in developing/underdeveloped countries. This study reports the prevalence and risk determinants of brucellosis in small ruminants of peri-urban and rural areas of district Multan, Southern Punjab, Pakistan. For this purpose, sera samples (n = 392) of small ruminants were collected and subjected to preliminary screening using commercially available RBPT reagents followed by serodetection of brucellosis using multispecies i-ELISA kit (ID.vet, France). All the ELISA positive samples were confirmed by PCR using genus-specific primers, and frequencies of Brucella species in positive samples were enumerated using species-specific primers. Results indicated seropositivity rates of 9.69, 9.95, and 10.20% in study population using RBPT reagents of IDEXX-USA, ID.Vet-France, and VRI-Pakistan, respectively, with a statistically nonsignificant difference (p > 0.05). Results of ELISA showed an overall seroprevalence rate of 7.14% in target population with a slightly higher rate in sheep (7.65%) as compared to goat (6.63%) population (p = 0.695; OR = 1.16, 95% CI = 0.53, 2.57). Results revealed that out of total positive samples, B. abortus was detected in 60.71% of seropositive samples and B. melitensis was detected in 14.28% of positive samples. It was revealed that risk factors including body condition scores, hygienic conditions of the housing facility, farming system, reproductive disorders, educational status of farmers, and awareness of farmers about brucellosis had significant association with brucellosis in small ruminants of study area (p < 0.05). Conversely, farm/herd size, locality, gender, age, weight, and parity showed a nonsignificant association (p > 0.05) with brucellosis. In conclusion, brucellosis is prevalent in small ruminants of Multan, Pakistan. It is recommended to devise and implement effective control strategies with a major focus on raising awareness about brucellosis in farmers for the containment of infection in the region.

11.
Cancer Invest ; 41(8): 739-749, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37782113

RESUMO

RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered tumors. We searched PubMed, Embase, Cochrane, WOS, and Clinicaltrials.gov. Objective-response, complete-response, and partial-response were 60-89%, 0-11%, and 55-89%, respectively, with the use of RET-specific drugs. ≥Grade 3 adverse events were seen in 28-53% of the patients, with hypertension, change in ALT, QT prolongation, neutropenia, and pneumonitis among the common side effects. Hence, selpercatinib and pralsetinib were effective and well tolerated by most of the patients with RET-altered tumors.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hipertensão , Neoplasias Pulmonares , Neoplasias , Neutropenia , Humanos , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-ret/genética
12.
Nat Chem Biol ; 17(4): 438-447, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33707782

RESUMO

Many biochemical reactions require controlled recruitment of proteins to membranes. This is largely regulated by posttranslational modifications. A frequent one is S-acylation, which consists of the addition of acyl chains and can be reversed by poorly understood acyl protein thioesterases (APTs). Using a panel of computational and experimental approaches, we dissect the mode of action of the major cellular thioesterase APT2 (LYPLA2). We show that soluble APT2 is vulnerable to proteasomal degradation, from which membrane binding protects it. Interaction with membranes requires three consecutive steps: electrostatic attraction, insertion of a hydrophobic loop and S-acylation by the palmitoyltransferases ZDHHC3 or ZDHHC7. Once bound, APT2 is predicted to deform the lipid bilayer to extract the acyl chain bound to its substrate and capture it in a hydrophobic pocket to allow hydrolysis. This molecular understanding of APT2 paves the way to understand the dynamics of APT2-mediated deacylation of substrates throughout the endomembrane system.


Assuntos
Membrana Celular/metabolismo , Tioléster Hidrolases/metabolismo , Tioléster Hidrolases/fisiologia , Acilação/fisiologia , Células HeLa , Humanos , Lipoilação/fisiologia , Processamento de Proteína Pós-Traducional , Transporte Proteico/fisiologia , Proteínas/metabolismo , Especificidade por Substrato , Tioléster Hidrolases/genética
13.
Cell Commun Signal ; 21(1): 149, 2023 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-37337213

RESUMO

BACKGROUND: The Hippo pathway plays a critical role in controlled cell proliferation. The tumor suppressor Merlin and large tumor suppressor kinase 1 (LATS1) mediate activation of Hippo pathway, consequently inhibiting the primary effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Phosphatidylinositol 4,5-bisphosphate (PIP2), a lipid present in the plasma membrane (PM), binds to and activates Merlin. Phosphatidylinositol 4-phosphate 5-kinase α (PIP5Kα) is an enzyme responsible for PIP2 production. However, the functional role of PIP5Kα in regulation of Merlin and LATS1 under Hippo signaling conditions remains unclear. METHODS: PIP5Kα, Merlin, or LATS1 knockout or knockdown cells and transfected cells with them were used. LATS1, YAP, and TAZ activities were measured using biochemical methods and PIP2 levels were evaluated using cell imaging. Low/high cell density and serum starvation/stimulation conditions were tested. Colocalization of PIP5Kα and PIP2 with Merlin and LATS1, and their protein interactions were examined using transfection, confocal imaging, immunoprecipitation, western blotting, and/or pull-down experiments. Colony formation and adipocyte differentiation assays were performed. RESULTS: We found that PIP5Kα induced LATS1 activation and YAP/TAZ inhibition in a kinase activity-dependent manner. Consistent with these findings, PIP5Kα suppressed cell proliferation and enhanced adipocyte differentiation of mesenchymal stem cells. Moreover, PIP5Kα protein stability and PIP2 levels were elevated at high cell density compared with those at low cell density, and both PIP2 and YAP phosphorylation levels initially declined, then recovered upon serum stimulation. Under these conditions, YAP/TAZ activity was aberrantly regulated by PIP5Kα deficiency. Mechanistically, either Merlin deficiency or LATS1 deficiency abrogated PIP5Kα-mediated YAP/TAZ inactivation. Additionally, the catalytic domain of PIP5Kα directly interacted with the band 4.1/ezrin/radixin/moesin domain of Merlin, and this interaction reinforced interaction of Merlin with LATS1. In accordance with these findings, PIP5Kα and PIP2 colocalized with Merlin and LATS1 in the PM. In PIP5Kα-deficient cells, Merlin colocalization with PIP2 was reduced, and LATS1 solubility increased. CONCLUSIONS: Collectively, our results support that PIP5Kα serves as an activator of the Hippo pathway through interaction and colocalization with Merlin, which promotes PIP2-dependent Merlin activation and induces local recruitment of LATS1 to the PIP2-rich PM and its activation, thereby negatively regulating YAP/TAZ activity. Video Abstract.


Assuntos
Via de Sinalização Hippo , Proteínas Serina-Treonina Quinases , Proteínas Serina-Treonina Quinases/metabolismo , Neurofibromina 2/metabolismo , Transdução de Sinais , Proteínas de Ciclo Celular/metabolismo , Fosfatos/metabolismo , Membrana Celular/metabolismo , Lipídeos , Fosfoproteínas/metabolismo , Proliferação de Células
14.
Org Biomol Chem ; 21(48): 9530-9533, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38009012

RESUMO

A Pd-catalyzed selective tandem cyclization of the Ugi adduct via Buchwald-Hartwig/C-H bond functionalization reactions has been reported. This sequence offers an interesting approach for synthesizing a wide range of pyrido[1,2-a]pyrazine-3,6-dione scaffolds under mild reaction conditions in moderate to excellent yields. The scope and limitations of the protocol are discussed.

15.
Nanotechnology ; 34(29)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37075709

RESUMO

The performance of the Graphene/Si (Gr/Si) Schottky interface and its potential in future electronics strongly rely on the quality of interconnecting contacts with external circuitry. In this work, we investigate the dominating and limiting factors of Gr/Si interfaces designed for high light absorption, paying particular attention to the nature of the contact failure under high electrostatic discharge (ESD) conditions. Our findings indicate that severe current crowding at contact edges of the graphene is the dominating factor for the device breakdown. Material degradation and electrical breakdown are systematically analyzed by atomic force, Raman, scanning electron, and energy-dispersive x-ray spectroscopies. This work enlists the robustness and limitations of Gr/Si junction in photodiode architecture under high ESD conditions that can be used as general guidelines for 2D-3D electronic and optoelectronic devices.

16.
Lung ; 201(2): 171-179, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37009923

RESUMO

Respiratory tract infection (RTI) remains a significant cause of morbidity and mortality across the globe. The optimal management of RTI relies upon timely pathogen identification via evaluation of respiratory samples, a process which utilises traditional culture-based methods to identify offending microorganisms. This process can be slow and often prolongs the use of broad-spectrum antimicrobial therapy, whilst also delaying the introduction of targeted therapy as a result. Nanopore sequencing (NPS) of respiratory samples has recently emerged as a potential diagnostic tool in RTI. NPS can identify pathogens and antimicrobial resistance profiles with greater speed and efficiency than traditional sputum culture-based methods. Increased speed to pathogen identification can improve antimicrobial stewardship by reducing the use of broad-spectrum antibiotic therapy, as well as improving overall clinical outcomes. This new technology is becoming more affordable and accessible, with some NPS platforms requiring minimal sample preparation and laboratory infrastructure. However, questions regarding clinical utility and how best to implement NPS technology within RTI diagnostic pathways remain unanswered. In this review, we introduce NPS as a technology and as a diagnostic tool in RTI in various settings, before discussing the advantages and limitations of NPS, and finally what the future might hold for NPS platforms in RTI diagnostics.


Assuntos
Sequenciamento por Nanoporos , Nanoporos , Infecções Respiratórias , Humanos , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , Antibacterianos/uso terapêutico , Metagenômica/métodos
17.
Skin Res Technol ; 29(11): e13519, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38009027

RESUMO

Automatic classification of Lyme disease rashes on the skin helps clinicians and dermatologists' probe and investigate Lyme skin rashes effectively. This paper proposes a new in-depth features fusion system to classify Lyme disease rashes. The proposed method consists of two main steps. First, three different deep learning models, Densenet201, InceptionV3, and Exception, were trained independently to extract the deep features from the erythema migrans (EM) images. Second, a deep feature fusion mechanism (meta classifier) is developed to integrate the deep features before the final classification output layer. The meta classifier is a basic deep convolutional neural network trained on original images and features extracted from base level three deep learning models. In the feature fusion mechanism, the last three layers of base models are dropped out and connected to the meta classifier. The proposed deep feature fusion method significantly improved the classification process, where the classification accuracy was 98.97%, which is particularly impressive than the other state-of-the-art models.


Assuntos
Doença de Lyme , Redes Neurais de Computação , Humanos , Pele , Doença de Lyme/diagnóstico
18.
Sensors (Basel) ; 23(11)2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37299734

RESUMO

This study describes an applied and enhanced real-time vehicle-counting system that is an integral part of intelligent transportation systems. The primary objective of this study was to develop an accurate and reliable real-time system for vehicle counting to mitigate traffic congestion in a designated area. The proposed system can identify and track objects inside the region of interest and count detected vehicles. To enhance the accuracy of the system, we used the You Only Look Once version 5 (YOLOv5) model for vehicle identification owing to its high performance and short computing time. Vehicle tracking and the number of vehicles acquired used the DeepSort algorithm with the Kalman filter and Mahalanobis distance as the main components of the algorithm and the proposed simulated loop technique, respectively. Empirical results were obtained using video images taken from a closed-circuit television (CCTV) camera on Tashkent roads and show that the counting system can produce 98.1% accuracy in 0.2408 s.


Assuntos
Algoritmos , Sistemas Computacionais , Inteligência
19.
J Pak Med Assoc ; 73(4): 869-871, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37052002

RESUMO

Serum Magnesium plays a significant role in different diabetic complications. This comparative cross sectional study was conducted to evaluate serum magnesium levels in patients with Type 2 Diabetes Mellitus (T2DM) with and without nephropathy. A total of 182 diabetic patients (91 with nephropathy and 91 without nephropathy) were included. Odds ratio were calculated and Mann Whitney U test was used to compare quantitative variables; p<0.05 was considered significant. The results showed that 64/91 (70.3%) patients with nephropathy had hypomagnesaemia as compared to 21/91 (23.07%) patients without nephropathy. The risk of hypomagnesaemia was higher in patients with nephropathy than without nephropathy (Odds ratio 2.7 vs 0.34). Median magnesium levels (1.73 mg/dl) were lower in patients with nephropathy as compared to patients without nephropathy (2.09 mg/dl), p<0.01. It is concluded that magnesium levels were significantly lower in patients with diabetic nephropathy as compared to without nephropathy.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Magnésio , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Transversais , Laboratórios Clínicos , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/complicações
20.
Trop Anim Health Prod ; 55(5): 348, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37796385

RESUMO

The study aimed to analyze the impact of calcium butyrate supplementation in calf starter on growth performance indices associated with early rumen development to decrease the volume of milk or milk replacer feeding and enhance early starter intake in Holstein calves. For this purpose, twelve Holstein calves were randomly assigned into three treatments (n = 4/treatment); a control without coated calcium butyrate, T1, and T2 treatments supplemented with coated calcium butyrate 3 g and 6 g per day/head, respectively. Body weight was measured at days 7, 14, 21, 28, 35, 42, 49, and 56 of the trial, and the average daily weight gain and feed conversion ratio were determined. Blood samples were collected at 14, 28, 42, and 56 days of trial for serological parameters. Gut morphometry was performed at the end of trial at slaughtering by collecting duodenal samples. Furthermore, the meat was also evaluated for its quality parameters including pH and tenderness after slaughtering. The results indicated that the feed intake, average daily weight gain, feed conversion ratio, and gut morphometric parameters involving villus height and crypts depth of calves were improved in coated calcium butyrate-supplemented groups. Furthermore, the supplementation of calf starter with coated calcium butyrate significantly enhanced serum concentrations of glucose and total protein. Besides, Beta hydroxy butyrate (BHBA) levels of blood were also found to be elevated in both treatment groups. However, it was revealed that coated calcium butyrate supplementation had no significant effect on meat quality parameters. In conclusion, the supplementation of calf starter with coated calcium butyrate could improve calf performance.


Assuntos
Butiratos , Cálcio , Animais , Bovinos , Desmame , Cálcio da Dieta , Aumento de Peso
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