Browse Articles

Decoding the diagnostic biomarkers of mitochondrial dysfunction related gene variants in pediatric T cell acute lymphoblastic leukemia

A novel assay incorporating CRISPR with RPA in a single pot for visual and accurate detection of Aphelenchoides besseyi in soybean

Hinokiflavone is a novel CK2 inhibitor promoting apoptosis and synergizing with chemotherapeutic agents in cisplatin resistant bladder cancer cells

Synthesis, characterization, anti-proliferative, and apoptotic activity of a novel quinazoline-containing 1,2,3-triazole toward three human cancer cells

Abstract A novel quinazoline-containing 1,2,3-triazole (4-TCPA) was synthesized to target VEGFR2 signaling for cancer treatment. Although current VEGFR2 inhibitors exhibit strong anticancer activity, their clinical use is limited due to severe side effects. Structural analysis of effective VEGFR2 inhibitors guided the design of 4-TCPA, ensuring the retention of Erlotinib’s essential pharmacophoric features for optimal receptor binding. The compound was tested for its anticancer efficacy against A549 (lung cancer), MCF7 (breast cancer), K562 (leukemia), and human normal fibroblast HFF2 cells. 4-TCPA demonstrated inhibitory activity in nearly all assays, with IC50 concentrations of 35.70 μM for A549, 19.50 μM for MCF7, 5.95 μM for K562, and 135.2 μM for HFF2. Further in vitro biological evaluations examined its mechanistic impact on EGFR, mTOR, Akt, MAPK, and PIK3CA. Apoptotic activity was assessed through Annexin V/PI double staining and caspase-3/7 activation, confirming its ability to induce both early and late apoptosis. Additionally, real-time quantitative PCR (qRT-PCR) was conducted to evaluate the expression levels of Akt, mTOR, MAPK, PIK3CA, EGFR, and VEGFR2. Results showed that 4-TCPA down-regulates these targets in a time-dependent manner, triggering apoptosis across all tested cancer cell lines. The study suggests that 4-TCPA may serve as a promising anticancer agent due to its targeted VEGFR2 inhibition and apoptotic induction, warranting further investigation. These findings support the potential of 4-TCPA as an effective treatment strategy for various cancers.

Deep learning model for grading carcinoma with Gini-based feature selection and linear production-inspired feature fusion

Cerebellar reaching ataxia is exacerbated by timing demands and assistive interaction torques

Optimizing rainfed cropping patterns for economic and environmental sustainability in East Lorestan Iran using GIS and LCA

Characterization of hotspot formation in AlGaN/GaN HEMTs by probing Raman scattering through an optically transparent gate

AlGaN/GaN high electron mobility transistors (HEMTs) are in high demand for wireless communication and power conversion applications due to their high-power and high-frequency capabilities. However, the extremely high operational heat flux often leads to the formation of hotspots that negatively impact the device performance and reliability. In this work, an AlGaN/GaN HEMT with a transparent indium tin oxide (ITO) gate was fabricated to enable in situ characterization of the channel peak temperature that occurs underneath the gate electrode. Raman thermometry was performed to measure the temperature of the GaN layer under various bias conditions while power dissipation was kept constant. An electro-thermal device model was created to validate experimental results, to explain the physical origins of the bias-dependent self-heating behavior, and to calculate the peak temperature of the two-dimensional electron gas channel. Experimental results show that the temperature measured next to the drain side edge of the gate (which is a normal practice when characterizing a standard metal-gated device) resulted in a 32% lower value than the temperature underneath the drain end of the gate acquired from the ITO-gated device. This underestimation of temperature could result in overestimation of the component lifetime during accelerated operational life tests.

EIAV encodes an accessory protein that antagonizes the host restriction factor equine tetherin

Equine infectious anemia virus (EIAV) is an important model for the study of pathogenesis in lentiviruses. Studies of viral genome organization and replication mechanisms are fundamental to the understanding of virus pathogenicity. In this study, we identified an unique transcript from EIAV in vivo and in vitro by Sanger sequencing and Northern blotting. The transcript contains a complete open reading frame and has length 369 nt. We named the protein encoded by this transcript S4 and demonstrated its expression in EIAV-infected cells. An S4-deficient EIAV infectious clone displayed obviously impaired virion release and attenuated virus replication in vitro, demonstrating that S4 plays a role in the release step of EIAV. The host restriction factor tetherin has broad-spectrum antiviral activity and prevents the release of a wide range of enveloped viruses, including lentiviruses. Here, we demonstrated that S4 enhances the release of the EIAV-like particle by counteracting the equine tetherin (eqTHN). S4 interacts with the eqTHN and sequesters it within intracellular membrane compartments, attenuating eqTHN expression on the cell surface and thereby disrupting its antiviral activity. Further investigation revealed that S4 retains eqTHN in the endoplasmic reticulum and trans-Golgi network through impacting its anterograde transport to the cell surface and may interfere with the posttranslational modification of this membrane protein. Collectively, our findings uncover an accessory protein, S4, of EIAV and reveal its ability to promote virion release by antagonizing the antiviral activity of the host restriction factor tetherin.

Context-invariant socioemotional encoding by prefrontal ensembles

Abstract The prefrontal cortex plays a key role in social interactions, anxiety-related avoidance, and flexible context-dependent behaviors, raising the question: How do prefrontal neurons represent socioemotional information across different environments? Are contextual and socioemotional representations segregated or intermixed, and does this cause socioemotional encoding to remap or generalize across environments? To address this, we imaged neuronal activity in the ventromedial prefrontal cortex of mice engaged in social interactions or anxiety-related avoidance within different environments. Neuronal ensembles representing context and social interaction overlapped more than expected by chance while nevertheless remaining largely orthogonal. Anxiety-related representations similarly generalized across environments while remaining largely orthogonal to contextual information. This shows how the ventromedial prefrontal cortex multiplexes parallel information streams using overlapping ensembles rather than transmitting information through largely distinct populations, thereby achieving context-invariant encoding alongside the context-specific reorganization of population-level activity.

Mapping previously undetected trees reveals overlooked changes in pan-tropical tree cover

A pendulum-based nanogenerator for high-entropy wave energy harvesting

Disease burden of bladder cancer in China and the different SDI regions over the world from 1990 to 2021

Cross-correlation-based signal pruning method (CCSPM) for effective signal distortion reduction in massive MIMO communications

Long term proliferation and physiological response of embryogenic callus in Slash pine (Pinus Elliottii Engelm)

Abstract Slash pine (Pinus elliottii Engelm.) is an economically significant tree species valued for its timber and resin production. Establishing a somatic embryogenesis system is essential for the effective utilization of slash pine. This study aims to develop an optimized cultivation system for the long-term proliferation of embryogenic callus (EC) in slash pine. The study used the EC induced from immature zygotic embryos as materials to investigated the effects of plant growth regulators (PGRs), subculture cycles, and subculture durations on the EC proliferation coefficient and the number of somatic embryos (SE). Additionally, we monitored the changes in the proliferation coefficient, the number of SE, and physiological and biochemical indicators of EC during long-term proliferation. The EC proliferation coefficient reached its highest value (7.65) when the DCR medium was supplemented with 1.0 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) and 1.0 mg/L 6-benzylaminopurine (6-BA). Refreshing the culture medium every 14 days, EC maintaining proliferation coefficient (4.05) and embryogenic potential for approximately three year (980 d), but the number of somatic embryos was low and significantly declined after 140 days.The additional supplementation of 1.0 mg/L 2- (1-naphthyl) acetic acid (NAA) to the original proliferation medium further enhanced SE induction, achieving a maximum of 143.25 SE per gram of EC. Under the optimal proliferation culture conditions, EC was subcultured for 392 days, with no significant differences observed in the proliferation coefficient and the number of SE. The results of correlation and path analyses between physiological indicators and proliferation coefficient indicate that the proliferation coefficient of EC is mainly related to the content of storage substances (starch and soluble sugars) and the activities of redox-related enzymes (POD and CAT). The optimized long-term proliferation culture system for EC in slash pine provides an efficient approach to enhance the production of EC and SE.

Efficient curve fitting with penalized B-splines for oceanographic and ecological applications

Incidence of palliative treatment among breast cancer patients undergoing neoadjuvant therapy: an analysis of the Brazilian public health system

Abstract Breast cancer is the leading cause of cancer-related deaths among women globally, including Brazil. This study assesses neoadjuvant treatment patterns, the impact of new therapies, and factors determining palliative care for patients who failed initial treatments. A historical cohort study using secondary data from DATASUS (2008–2017) focused on women aged 18–90 with stages II and III breast cancer who received neoadjuvant treatment. Data on chemotherapy, hormonal therapy, and anti-HER2 treatment were analyzed. The Palliative Treatment Rate (PTR) was calculated by cross-referencing neoadjuvant treatment records with subsequent palliative care records, indicating cases where the initial curative intent was not achieved. The study included 71,181 patients, with a mean age of 51.5 years. Most were diagnosed at Stage III (85%). Anti-HER2 therapy was introduced in 2013, with 10.5% receiving it. The 5-year PTR decreased from 44% (2008–2012) to 36% (2013–2017). The combination of chemotherapy, endocrine therapy, and anti-HER2 therapy had the lowest PTR. Logistic regression identified younger age, higher histological grade, Stage III disease, and compromised lymph nodes as factors increasing the likelihood of needing palliative care, while HER2 positivity and hormonal therapy reduced it. Regional disparities were observed, with patients from the Southeast more likely to receive palliative care. Early diagnosis and access to anti-HER2 therapy significantly reduce palliative care needs. Socio-economic and regional disparities in treatment highlight the need for equitable access to diagnostic tools and therapies to improve survival outcomes in Brazil’s public healthcare system.

Flexible carbon-fiber/g-C3N4 nanosheet array as recyclable photocatalysts and photoelectrocatalysts

Identification of clusters related to programmed cell death and potential prognostic biomarkers for immunotherapy response in endometrial cancer

Dopaminergic and serotonergic genetic variants predict actions and expectations of cooperation and punishment

Abstract Genetic variants in dopaminergic and serotonergic pathways have been linked to individual differences in social behavior. In this study, we investigated the relationship between eight allelic variants within these pathways and both behavior and beliefs in 99 participants playing an online Public Goods Game (PGG) with and without punishment. Our results show that individuals with the 5-HTTLPR L/L genotype contributed less and had lower expectations of others’ contributions in the absence of punishment; the 5-HTR1B-rs13212041 T/T genotype was associated with lower expectations of antisocial and spiteful punishment; the COMT-rs4680 A/A (Met/Met) genotype was linked to lower expectations of contributions in the presence of punishment. These findings suggest that specific alleles modulate both cooperative behavior and social expectations, suggesting a genetic contribution to individual variability in responses to social dilemmas.