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Watermelon (Citrullus lanatus) is the third largest fruit crop in the world in term of production. However, it is susceptible to several viruses. Watermelon vine decline (WVD), caused by whitefly-transmitted squash vein yellowing virus (SqVYV), is a disease that has caused over $60 million in losses in the US and continues to occur regularly in southeastern states. Understanding the molecular mechanisms underlying resistance to SqVYV is important for effective disease management. A time-course transcriptomic analysis was conducted on resistant (392291-VDR) and susceptible (Crimson Sweet) watermelon genotypes inoculated with SqVYV. Significantly higher levels of SqVYV were observed over time in the susceptible compared to the resistant genotype. The plasmodesmata callose binding protein (PDCB) gene, which is responsible for increased callose deposition in the plasmodesmata, was more highly expressed in the resistant genotype than in the susceptible genotype before and after inoculation, suggesting the inhibition of cell-to-cell movement of SqVYV. The potential role of the RNA interference (RNAi) pathway was observed in the resistant genotype based on differential expression of eukaryotic initiation factor (eIF), translin, DICER, ribosome inactivating proteins, RNA-dependent RNA polymerase (RDR), and Argonaute (AGO) genes after inoculation. The significant differential expression of hormone-related genes, including those involved in the ethylene, jasmonic acid, auxin, cytokinin, gibberellin, and salicylic acid signaling pathways, was observed, emphasizing their regulatory roles in the defense response. Genes regulating pectin metabolism, cellulose synthesis, cell growth and development, xenobiotic metabolism, and lignin biosynthesis were overexpressed in the susceptible genotype, suggesting that alterations in cell wall integrity and growth processes result in disease symptom development. These findings will be helpful for further functional studies and the development of SqVYV-resistant watermelon cultivars.
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Although the role of G-quadruplex (G4) DNA structures has been suggested in chromosomal looping this was not tested directly. Here, to test causal function, an array of G4s, or control sequence that does not form G4s, were inserted within chromatin in cells. In vivo G4 formation of the inserted G4 sequence array, and not the control sequence, was confirmed using G4-selective antibody. Compared to the control insert, we observed a remarkable increase in the number of 3D chromatin looping interactions from the inserted G4 array. This was evident within the immediate topologically associated domain (TAD) and throughout the genome. Locally, recruitment of enhancer histone marks and the transcriptional coactivator p300/Acetylated-p300 increased in the G4-array, but not in the control insertion. Resulting promoter-enhancer interactions and gene activation were clear up to 5 Mb away from the insertion site. Together, these show the causal role of G4s in enhancer function and long-range chromatin interactions. Mechanisms of 3D topology are primarily based on DNA-bound architectural proteins that induce/stabilize long-range interactions. Involvement of the underlying intrinsic DNA sequence/structure in 3D looping shown here therefore throws new light on how long-range chromosomal interactions might be induced or maintained.
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Cromatina , Quadruplex G , Regiões Promotoras Genéticas , Cromatina/metabolismo , Cromatina/química , Cromatina/genética , Humanos , Histonas/metabolismo , Histonas/química , Histonas/genética , Elementos Facilitadores GenéticosRESUMO
The adoption of sustainable agricultural practices is increasingly imperative in addressing global food security and environmental concerns, with microbial based bio-inoculums emerging as a promising approach for nurturing soil health and fostering sustainable crop production.This review article explores the potential of microbial based bio-inoculumsor biofertilizers as a transformative approach toenhance plant disease resistance and growth. It explores the commercial prospects of biofertilizers, highlighting their role in addressing environmental concerns associated with conventional fertilizers while meeting the growing demand for eco-friendly agricultural practices. Additionally, this review discusses the future prospects of biofertilizers, emphasizing the ongoing advancements in biotechnology and formulation techniques that are expected to enhance their efficacy and applicability. Furthermore, this article provides insights into strategies for the successful acceptance of biofertilizers among farmers, including the importance of quality control, assurance, and education initiatives to raise awareness about their benefits and overcome barriers to adoption. By synthesizing the current research findings and industrial developments, this review offers valuable guidance for stakeholders seeking to exploit the potential of biofertilizers or beneficial microbes to promote soil health, ensure sustainable crop production, and addressing the challenges of modern agriculture.
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Chiral molecules, a cornerstone of chemical sciences with applications ranging from pharmaceuticals to molecular electronics, come in mirror-image pairs called enantiomers. However, their synthesis often requires complex control of their molecular geometry. We propose a strategy called "electromagnetic enantiomers" for inducing chirality in molecules located within engineered nanocavities using light, eliminating the need for intricate molecular design. This approach works by exploiting the strong coupling between a nonchiral molecule and a chiral mode within a nanocavity. We provide evidence for this strong coupling through angular emission patterns verified by numerical simulations and with complementary evidence provided by luminescence lifetime measurements. In simpler terms, our hypothesis suggests that chiral properties can be conveyed on to a molecule with a suitable chromophore by placing it within a specially designed chiral nanocavity that is significantly larger (hundreds of nanometers) than the molecule itself. To demonstrate this concept, we showcase an application in display technology, achieving efficient emission of circularly polarized light from a nonchiral molecule. The electromagnetic enantiomer concept offers a simpler approach to chiral control, potentially opening doors for asymmetric synthesis.
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BACKGROUND: Apart from direct portal pressure reduction, non-selective beta-blockers (NSBB) modulate inflammatory response, which could be beneficial in patients with acute decompensation (AD). We therefore aimed to evaluate the effect of NSBB on 28-day mortality and markers of systemic inflammation in a propensity score-matched (PSM) cohort of AD patients requiring intensive care unit (ICU) admission. METHODS: Patients were recruited from registry of AD patients requiring ICU admission. Out of total 445 patients, 108 patients on NSBB before admission (NSBB use group) were PSM for age, gender, pre-admission Child-Turcotte-Pugh score and history of previous decompensation to 108 patients not on NSBB (non-NSBB use group) which served as the control group. ICU parameters, markers of systemic inflammation and 28-day mortality were compared by standard statistical tests. RESULTS: After PSM, no difference was observed in aetiology of cirrhosis, or precipitating event for AD between the groups. Pre-admission creatinine, bilirubin, international normalised ratio and haemoglobin were similar between the groups, whereas pre-admission white cell count (WCC) and neutrophil to lymphocyte ratio (NLR) was lower in NSBB-group. On admission to ICU, NSBB group had lower heart rate (p = 0.006), platelets (p = 0.012), WCC (p = 0.006), NLR (p = 0.039) and C-reactive protein (p = 0.007). Significantly more community acquired bacterial infections (p = 0.006), renal failure (p = 0.033) and higher grades of acute-on-chronic liver failure (ACLF; p = 0.012) were observed in non-NSBB group. Significantly lower 28-day (p = 0.001) and 90-day (p = 0.002) mortality was seen in NSBB group. Univariate and multivariable analysis for 28-day mortality showed that while ACLF at presentation and community acquired bacterial infection were independent negative predictors, prior NSBB use was positive predictors of survival. CONCLUSIONS: Prior use of NSBB is associated with improved 28- and 90-day mortality in critically ill cirrhosis patients with AD which is mediated probably by blunting of the inflammatory response.
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Breast cancer (BC) has emerged as the most common malignancy among females. The genomic profile of BC is diverse in nature and complex due to heterogeneity among various geographically different ethnic groups. The primary objective of this study was to carry out a comprehensive mutational analysis of Indian BC cases by performing whole exome sequencing. The cohort included patients with a median age of 48 years. TTN, TP53, MUC16, SYNE1, and OBSCN were the frequently altered genes found in our cohort. The PIK3CA and KLC3 genes are driver genes implicated in various cellular functions and cargo transportation through microtubules, respectively. Except for CCDC168 and PIK3CA, several gene pairings were found to be significantly linked with co-occurrence. Irrespective of their hormonal receptor status, RTK/RAS was observed with frequently altered signaling pathways. Further analysis of the mutational signature revealed that SBS13, SBS6, and SBS29 were mainly observed in our cohort. This study supplements the discovery of diagnostic biomarkers and provides new therapeutic options for the improved management of BC.
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Neoplasias da Mama , Sequenciamento do Exoma , Mutação , Humanos , Feminino , Neoplasias da Mama/genética , Pessoa de Meia-Idade , Adulto , Índia/epidemiologia , Biomarcadores Tumorais/genética , Idoso , Análise Mutacional de DNARESUMO
Background: Sculpting is a common occupation in India. However, there have been no studies from India on sculpting-related silicosis. Aims: The aims of this study were to evaluate- 1. awareness of disease related to sculpting. 2. Clinical, radiological, and physiological parameters in "sculpting workers" suffering from silicosis. Settings and Design: This was a retrospective evaluation of data collected during compensation visits for silicosis in workers of the sculpting industries. Methods and Material: The data were collected between January 2021 to April 2023. A total of 114 patients were evaluated. All patients underwent clinical evaluation including awareness about the disease, chest radiography, high-resolution computed tomography (HRCT) scan of the chest, and spirometry. Results: The majority of patients (109) (95%) did not use any personal protective equipment while at work and did not have any awareness regarding preventive measures. On chest radiography, small opacities (rounded or irregular) and large opacities were seen in 84 (73.7%) and 26 (22.8%) patients, respectively. The size of large opacities was significantly proportionate with duration of job (P = 0.019). HRCT chest was more sensitive compared to chest radiographs. 94 (82.4%) patients were having abnormal spirometric findings. Conclusions: The benefits of prevention of silica dust exposure and patient education considerably outweigh the benefits of early detection and treatment of silicosis, as there was an increase in the size of lesions with increasing duration of exposure. There should be a national health program on silicosis to protect worker's health.
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Diffuse Large B-cell lymphoma (DLBCL) includes the Activated B-cell-like (ABC) and Germinal Center B-cell-like (GCB) subtypes, which differ in cell-of-origin, genetics and clinical response. By screening the subtype-specific activity of 211 drugs approved or in active clinical development for other diseases, we identified inhibitors of nicotinamide phosphoribosyl transferase (NAMPTi) as active in a subset of GCB-DLBCLs in vitro and in vivo. We validated three chemically distinct NAMPTi for their on-target activity based on biochemical and genetic rescue approaches, and found the ratio between NAMPT:PARP1 RNA levels was predictive of NAMPTi sensitivity across DLBCL subtypes. Notably, the NAMPT:PARP1 transcript ratio predicts higher anti-tumor activity in BCL2-translocated GCB-DLBCL. Accordingly, pharmacological and genetic inhibition of BCL2 was potently synergistic with NAMPT blockade. These data support the inhibition of NAMPT as a therapeutically relevant strategy for BCL2-translocated DLBCLs.
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The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.
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Present study has been conducted to characterize the Mg alloy namely AZ31-based composite joined by Friction stir processing (FSP) technique. This study deals with the effect of single and double passes in FSP of AZ31 Mg alloy. The single pass run in FSP is followed at tool rotation speed (N) of 1000 to 1400 rpm. Also, the double pass run in FSP was followed at these speeds without using reinforcements. The feedstock particles namely SiC, Al2O3, Cr, and Si powders were used in fabrication process. The hardness, impact strength, and tensile strength characteristics were assessed in the stir region zone, and the results indicated significant improvement in these properties. The highest values of mechanical strength were seen in the FSPed area with N = 1000 rpm at a constant transverse speed (r) of 40 mm/min. Also, the tensile strength of the two passes FSPed plates is much higher than that of the single section without any reinforcement, as revealed in previous study also. The Scanning electron microscopy (SEM) analysis is done at two different magnifications for the Silicon carbide, Alumina, Chromium, and Silicon powder reinforced composites fabricated at speed of 1000 rpm. The microstructure shows that reinforced particles were uniform dispersed into FSPed region and agglomerated with Mg matrix. Si powder produces finer microstructure as compare to SiC, Al2O3, Cr. FSP decreases the grain size of processed material. Optical Microscopy results revealed that the reinforcement particle produced a homogenous microstructure and, a refined grain and equally dispersed in matrix material without split to the particle.
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OBJECTIVE: The purpose of this study was to determine the effect of osteoporosis medications on opportunistic CT-based Hounsfield units (HU). METHODS: Spine and nonspine surgery patients were retrospectively identified who had been treated with romosozumab for 3 to 12 months, teriparatide for 3 to 12 months, teriparatide for > 12 months, denosumab for > 12 months, or alendronate for > 12 months. HU were measured in the L1-4 vertebral bodies. One-way ANOVA was used to compare the mean change in HU among the five treatment regimens. RESULTS: In total, 318 patients (70% women) were included, with a mean age of 69 years and mean BMI of 27 kg/m2. There was a significant difference in mean HU improvement (p < 0.001) following treatment with romosozumab for 3 to 12 months (n = 32), teriparatide for 3 to 12 months (n = 30), teriparatide for > 12 months (n = 44), denosumab for > 12 months (n = 123), and alendronate for > 12 months (n = 100). Treatment with romosozumab for a mean of 10.5 months significantly increased the mean HU by 26%, from a baseline of 85 to 107 (p = 0.012). Patients treated with teriparatide for > 12 months (mean 23 months) experienced a mean HU improvement of 25%, from 106 to 132 (p = 0.039). Compared with the mean baseline HU, there was no significant difference after treatment with teriparatide for 3 to 12 months (110 to 119, p = 0.48), denosumab for > 12 months (105 to 107, p = 0.68), or alendronate for > 12 months (111 to 113, p = 0.80). CONCLUSIONS: Patients treated with romosozumab for a mean of 10.5 months and teriparatide for a mean of 23 months experienced improved spinal bone mineral density as estimated by CT-based opportunistic HU. Given the shorter duration of effective treatment, romosozumab may be the preferred medication for optimization of osteoporotic patients in preparation for elective spine fusion surgery.
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Heat stress has been shown to have a detrimental impact on testicular activity and spermatogenesis. Ellagic acid is a plant-derived organic compound that has a variety of biological functions. Thus, it is believed that ellagic acid may improve heat-stressed testicular dysfunction. There has been no research on the impact of ellagic acid on heat-stressed testicular dysfunction. The mice were divided into 4 groups. The first group was the normal control group (CN), and the second received heat stress (HS) by submerging the lower body for 15â¯min in a water bath with a thermostatically controlled temperature kept at 43°C (HS), and the third and fourth groups were subjected to heat-stress similar to group two and given two different dosages of ellagic acid (5â¯mg/kg (EH5) and 50â¯mg/kg (EH50) for 14 days. Ellagic acid at a dose of 50â¯mg/kg improved the level of circulating testosterone (increased 3ßHSD) and decreases the oxidative stress. The testicular and epididymal architecture along with sperm parameters also showed improvement. Ellagic acid treatment significantly increases the germ cell proliferation (GCNA, BrdU staining) and Bcl2 expression and decreases active caspase 3 expression. Heat stress downregulated the expression of AR, ER-α and ER-ß, and treatment with ellagic acid increased the expression of ER-α and ER-ß markers in the 50â¯mg/kg treatment group. Thus, our finding suggests that ellagic acid ameliorates heat-induced testicular impairment through modulating testosterone synthesis, germ cell proliferation, and oxidative stress. These effects could be manifested by regulating androgen and estrogen receptors. However, the two doses showed differential effects of some parameters, which require further investigation.
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Inflammation promotes solid tumor progression, but how regulatory mechanisms of inflammation may impact leukemia is less well studied. Using annexin A5 (ANXA 5), a calcium-binding protein known for apoptosis, which we discovered to be differentially expressed in the bone marrow microenvironment (BMM) of mice with acute myeloid (AML) versus chronic myeloid leukemia, as a model system, we unravel here a circuit in which AML-derived tumor necrosis factor (TNF)α dose-dependently reduces ANXA5 in the BMM. This creates an inflammatory BMM via elevated levels of prostaglandin E2 (PGE2). Via binding to its EP4 receptor, PGE2 increases ï¢-catenin and hypoxia-inducible factor (HIF) 1 α signaling in AML cells, thereby accelerating PGE2-sensitive AML. Human trephine biopsies may show lower ANXA5 expression and higher PGE2 expression in AML compared to other hematological malignancies. Further, syngeneic and xenogeneic transplantation models suggest a survival benefit after treatment with the inhibitor of prostaglandin-endoperoxide synthase 2 (cyclooxygenase 2 (COX2)), celecoxib, plus cytarabine in those AML types highly sensitive to PGE2 compared to cytarabine alone. Taken together, TNFα/ANXA5/NF-kB/COX2/PGE2-mediated inflammation influences AML course in a highly differential and circular manner, and AML patients with 'inflammatory AML' may benefit from antiphlogistic agents as adjunct therapy.
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Breast cancer (BC) is the most commonly diagnosed cancer among women. Chemo-, immune- and photothermal therapies are employed to manage BC. However, the tumor microenvironment (TME) prevents free drugs and nanocarriers (NCs) from entering the tumor premises. Formulation scientists rely on enhanced permeation and retention (EPR) to extravasate NCs in the TME. However, recent research has demonstrated the inconsistent nature of EPR among different patients and tumor types. In addition, angiogenesis, high intra-tumor fluid pressure, desmoplasia, and high cell and extracellular matrix density resist the accumulation of NCs in the TME. In this review, we discuss TME normalization as an approach to improve the penetration of drugs and NCSs in the tumor premises. Strategies such as normalization of tumor vessels, reversal of hypoxia, alleviation of high intra-tumor pressure, and infiltration of lymphocytes for the reversal of therapy failure have been discussed in this manuscript. Strategies to promote the infiltration of anticancer immune cells in the TME after vascular normalization have been discussed. Studies strategizing time points to administer TME-normalizing agents are highlighted. Mechanistic pathways controlling the angiogenesis and normalization processes are discussed along with the studies. This review will provide greater tumor-targeting insights to the formulation scientists.
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Design and development of efficient drug delivery technologies that impart site-specificity is the need of the hour for the effective treatment of lung cancer. The emergence of materials science and nanotechnology partially helped drug delivery scientists to achieve this objective. Various stimuli-responsive materials that undergo degradation at the pathological tumor microenvironment (TME) have been developed and explored for drug delivery applications using nanotechnological approaches. Nanoparticles (NPs), owing to their small size and high surface area to volume ratio, demonstrated enhanced cellular internalization, permeation, and retention at the tumor site. Such passive accumulation of stimuli-responsive materials helped to achieve spatiotemporally controlled and targeted drug delivery within the tumors. In this review, we discussed various stimuli-physical (interstitial pressure, temperature, and stiffness), chemical (pH, hypoxia, oxidative stress, and redox state), and biological (receptor expression, efflux transporters, immune cells, and their receptors or ligands)-that are characteristic to the TME. We mentioned an array of biomaterials-based nanoparticulate delivery systems that respond to these stimuli and control drug release at the TME. Further, we discussed nanoparticle-based combinatorial drug delivery strategies. Finally, we presented our perspectives on challenges related to scale-up, clinical translation, and regulatory approvals.
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BACKGROUND: In this observational study, clinical characteristics, etiologies, and outcomes of patients admitted to the hospital with community-acquired acute kidney injury (CAAKI) have been compared in contrast to those who hospital-acquired Acute Kidney Injury (HAAKI). METHODS: This was a prospective study of adults aged 18 years or above diagnosed with acute kidney injury (AKI) over a period of 17 months at a tertiary care hospital. RESULTS: 230 patients had AKI with the mean age of the study population being 45.33 ± 12.68 years. 178 (77.4%) patients were enrolled from medical unit, 25 (10.7%) from surgical unit, and 27 (11.7%) from obstetrical unit. The observed incidence of AKI was 15/1000 admissions. About 58.2% had CAAKI and 96 (43.7%) had HAAKI. Out of 230 patients, 170 (73.9%) patients were male and 60 (26.1%) were female. Sepsis was the most common (52.1%) etiology of AKI among the medical cases. Urosepsis, scrub typhus, and pneumonia were the most common causes of AKI. Sixty percent of AKI was Kidney Disease Improving Global Outcomes Stage 1 or 2 and 40% was in Stage 3. Oliguria was seen in 56.5%, hyperkalemia in 34.7%, fluid overload in 6.1%, and metabolic acidosis in 22.6%. The majority of patients had multiple organ involvement (52.1%) at the time of enrollment. About 116 (50.4%) had lung injury requiring mechanical ventilation and 95 (41.3%) were on inotropes. Mortality occurred in 19.5%. Anemia, the use of vasopressor drugs, and the need for intensive care support were independent predictive factors for mortality. CONCLUSION: AKI was common in hospitalized patients and leads to significant inhospital mortality. AKI is largely a CAAKI, and the lesser extent is due to HAAKI. Many causes are potentially preventable. Early fluid resuscitation, effective antibiotics, appropriate antidotes, and timely referral of established AKI patients to centers with dialysis facilities can improve AKI outcomes.
Résumé Contexte:Dans cette étude observationnelle, les caractéristiques cliniques, les étiologies et les résultats des patients admis à l'hôpital pour des affections aiguës d'origine communautaire. les lésions rénales (CAAKI) ont été comparées à celles qui ont contracté une lésion rénale aiguë à l'hôpital (HAAKI).Méthodes:Il s'agissait d'une étude prospective portant sur des adultes âgés de 18 ans ou plus ayant reçu un diagnostic d'insuffisance rénale aiguë (IRA) sur une période de 17 mois dans un hôpital de soins tertiaires.Résultats:230 patients avaient une IRA, l'âge moyen de la population étudiée étant de 45,33 ± 12,68 ans. 178 (77,4 %) patientes ont été recrutées dans l'unité médicale, 25 (10,7 %) dans l'unité chirurgicale et 27 (11,7 %) dans l'unité obstétricale. L'incidence observée de l'IRA était de 15/1 000 admissions. Environ 58,2 % avaient CAAKI et 96 (43,7 %) avaient HAAKI. Sur 230 patients, 170 (73,9 %) étaient des hommes et 60 (26,1 %) étaient des femmes. Le sepsis était l'étiologie d'IRA la plus courante (52,1 %) parmi les cas médicaux. L'urosepsie, le typhus des broussailles et la pneumonie étaient les causes les plus fréquentes d'AKI. Soixante pour cent des AKI étaient des maladies rénales améliorant les résultats globaux de stade 1 ou 2 et 40 % étaient au stade 3. Une oligurie a été observée dans 56,5 %, une hyperkaliémie dans 34,7 %, une surcharge hydrique dans 6,1 % et une acidose métabolique dans 22,6 %. La majorité des patients présentaient une atteinte de plusieurs organes (52,1 %) au moment de l'inscription. Environ 116 (50,4 %) souffraient de lésions pulmonaires nécessitant une ventilation mécanique et 95 (41,3 %) prenaient des inotropes. La mortalité est survenue dans 19,5%. L'anémie, l'utilisation de médicaments vasopresseurs et la nécessité d'un soutien en soins intensifs étaient des facteurs prédictifs indépendants de mortalité.Conclusion:L'IRA était fréquente chez les patients hospitalisés et entraîne une mortalité hospitalière significative. AKI est en grande partie un CAAKI, et dans une moindre mesure est dû au HAAKI. De nombreuses causes sont potentiellement évitables. Une réanimation liquidienne précoce, des antibiotiques efficaces, des antidotes appropriés et une orientation rapide des patients atteints d'IRA établis vers des centres dotés d'installations de dialyse peuvent améliorer les résultats de l'IRA.
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Injúria Renal Aguda , Centros de Atenção Terciária , Humanos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Feminino , Masculino , Índia/epidemiologia , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Centros de Atenção Terciária/estatística & dados numéricos , Incidência , Mortalidade Hospitalar , Sepse/epidemiologia , Sepse/complicações , Hospitalização/estatística & dados numéricos , Fatores de Risco , IdosoRESUMO
Accurate segmentation of the liver and tumors from CT volumes is crucial for hepatocellular carcinoma diagnosis and pre-operative resection planning. Despite advances in deep learning-based methods for abdominal CT images, fully-automated segmentation remains challenging due to class imbalance and structural variations, often requiring cascaded approaches that incur significant computational costs. In this paper, we present the Dual-Encoder Double Concatenation Network (DEDC-Net) for simultaneous segmentation of the liver and its tumors. DEDC-Net leverages both residual and skip connections to enhance feature reuse and optimize performance in liver and tumor segmentation tasks. Extensive qualitative and quantitative experiments on the LiTS dataset demonstrate that DEDC-Net outperforms existing state-of-the-art liver segmentation methods. An ablation study was conducted to evaluate different encoder backbones - specifically VGG19 and ResNet - and the impact of incorporating an attention mechanism. Our results indicate that DEDC-Net, without any additional attention gates, achieves a superior mean Dice Score (DS) of 0.898 for liver segmentation. Moreover, integrating residual connections into one encoder yielded the highest DS for tumor segmentation tasks. The robustness of our proposed network was further validated on two additional, unseen CT datasets: IDCARDb-01 and COMET. Our model demonstrated superior lesion segmentation capabilities, particularly on IRCADb-01, achieving a DS of 0.629. The code implementation is publicly available at this website.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Fígado , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Fígado/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico por imagem , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodosRESUMO
The increasing use of nanoparticles is driving the growth of research on their effects on living organisms. However, studies on the effects of nanoparticles on cellular respiration are still limited. The remodeling of cellular-respiration-related indices in plants induced by zinc oxide nanoparticles (nnZnO) and its bulk form (blZnO) was investigated for the first time. For this purpose, barley (Hordeum vulgare L.) seedlings were grown hydroponically for one week with the addition of test compounds at concentrations of 0, 0.3, 2, and 10â¯mgâ¯mL-1. The results showed that a low concentration (0.3â¯mgâ¯mL-1) of blZnO did not cause significant changes in the respiration efficiency, ATP content, and total reactive oxygen species (ROS) content in leaf tissues. Moreover, a dose of 0.3â¯mgâ¯mL-1 nnZnO increased respiration efficiency in both leaves (17â¯%) and roots (38â¯%). Under the influence of blZnO and nnZnO at medium (2â¯mgâ¯mL-1) and high (10â¯mgâ¯mL-1) concentrations, a dose-dependent decrease in respiration efficiency from 28â¯% to 87â¯% was observed. Moreover, the negative effect was greater under the influence of nnZnO. The gene transcription of the subunits of the mitochondria electron transport chain (ETC) changed mainly only under the influence of nnZnO in high concentration. Expression of the ATPase subunit gene, atp1, increased slightly (by 36â¯%) in leaf tissue under the influence of medium and high concentrations of test compounds, whereas in the root tissues, the atp1 mRNA level decreased significantly (1.6-2.9 times) in all treatments. A dramatic decrease (1.5-2.4 times) in ATP content was also detected in the roots. Against the background of overexpression of the AOX1d1 gene, an isoform of alternative oxidase (AOX), the total ROS content in leaves decreased (with the exception of 10â¯mgâ¯mL-1 nnZnO). However, in the roots, where the pressure of the stress factor is higher, there was a significant increase in ROS levels, with a maximum six-fold increase under 10â¯mgâ¯mL-1 nnZnO. A significant decrease in transcript levels of the pentose phosphate pathway and glycolytic enzymes was also shown in the root tissues compared to leaves. Thus, the disruption of oxidative phosphorylation leads to a decrease in ATP synthesis and an increase in ROS production; concomitantly reducing the efficiency of cellular respiration.
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Respiração Celular , Hordeum , Folhas de Planta , Raízes de Plantas , Espécies Reativas de Oxigênio , Óxido de Zinco , Óxido de Zinco/toxicidade , Hordeum/efeitos dos fármacos , Hordeum/genética , Folhas de Planta/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Raízes de Plantas/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Plântula/efeitos dos fármacos , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Nanopartículas/toxicidade , Nanopartículas Metálicas/toxicidade , Oxirredutases/genética , Oxirredutases/metabolismoRESUMO
Diabetic neuropathy (DN) is a neurodegenerative disorder that is primarily characterized by distal sensory loss, reduced mobility, and foot ulcers that may potentially lead to amputation. The multifaceted etiology of DN is linked to a range of inflammatory, vascular, metabolic, and other neurodegenerative factors. Chronic inflammation, endothelial dysfunction, and oxidative stress are the three basic biological changes that contribute to the development of DN. Although our understanding of the intricacies of DN has advanced significantly over the past decade, the distinctive mechanisms underlying the condition are still poorly understood, which may be the reason behind the lack of an effective treatment and cure for DN. The present study delivers a comprehensive understanding and highlights the potential role of the several pathways and molecular mechanisms underlying the etiopathogenesis of DN. Moreover, Schwann cells and satellite glial cells, as integral factors in the pathogenesis of DN, have been enlightened. This work will motivate allied research disciplines to gain a better understanding and analysis of the current state of the biomolecular mechanisms behind the pathogenesis of DN, which will be essential to effectively address every facet of DN, from prevention to treatment.
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Though there has been advancement in the management of lung cancer, it is not well utilized due to its limited availability and high cost. This is a prospective observational study done at a tertiary care center from January 2014 to December 2022, involving patients with primary lung cancer. After tumor-node-metastasis staging and molecular testing, the patients received chemotherapy, radiotherapy, surgery, targeted therapy, and immunotherapy in various combinations as per the prevailing National Comprehensive Cancer Network Guidelines. 92 patients were enrolled in the study, with the mean age being 58.94±10.33 and 72 (78.26%) being males. 69 (75%) patients were either current or former smokers. 78 (84.78%) patients had an Eastern Cooperative Oncology Group (ECOG) score of 0-2 while the remaining had an ECOG of 3-4. 80 (86.95%) patients had non-small cell lung cancer (NSCLC) [44 (47.83%) adenocarcinoma, 25 (27.17%) squamous cell carcinoma, and 11 (11.95%) NSCLC: not otherwise specified], while 12 (13.04%) patients had small cell lung cancer. One (1.08%) patient each presented in stage I and stage II, 31 (33.69%) patients presented in stage III, and 59 (64.13%) patients presented in stage IV. 44 patients with adenocarcinoma were subjected to mutational analysis, and an epidermal growth factor receptor mutation was found in 13 (29.5%) patients. None of the patients had ALK mutation, ROS-1 rearrangement, or BRAF mutation. PD-L1 expression was evaluated in 9 patients with NSCLC, and it was found in 6 (66.66%) patients. The overall mean survival was 12.7 months. The mean survival for patients with stages I, II, III, and IV was 70, 96, 8.1, and 12.7 months, respectively. Survival in stage IV was better than in stage III, as the eligible patients received targeted therapy and immunotherapy. Targeted therapy and immunotherapy have improved survival. Molecular analysis should be done whenever indicated, and eligible patients must be administered targeted therapy and immunotherapy.