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Nanoscale surface morphology modifications for next-generation supercritical CO2 heat exchangers: review and perspective
No full textCarbon nanotube (CNT) pin fin arrays, CNT, or nanoparticle coating have emerged in recent decades as novel techniques for enhancing heat transfer and reducing drag. In this paper, the suitability of these techniques is reviewed specifically for heat transfer enhancement and drag reduction in the gas side of supercritical carbon dioxide (SCO2) counterflow tube-in-tube or plate type heat exchangers for applications in CO2 refrigeration systems. The methodology and the applicability of various approaches for predicting the heat transfer rates and the frictional pressure drop associated with flow over a nanocoated surface have been reviewed. Findings from both experimental and numerical studies highlight critical limitations, including a lack of fundamental knowledge about flow over superhydrophobic surfaces and the absence of experimental data for crucial parameters such as temperature jump at the wall, velocity and temperature shifts, and the Reynolds analogy factor for nanotube or nanoparticle coatings in turbulent flow regimes. These limitations significantly hamper the predictive capabilities of both single-scale and multi-scale models for frictional pressure drops and heat transfer coefficients. To enhance the accuracy of these models, it is essential to consider surface parameters such as arithmetic mean roughness (Ra), root-mean-square roughness (Rq), effective slope (Es), skewness (Sk), and kurtosis (ku)
Harnessing the immunotherapeutic potentials of gamma delta T cells against hematological malignancies
No full textGamma delta (γδ) T cells, which constitute about 5%–10% of peripheral blood lymphocytes, play key roles in tumor immunosurveillance and are often enriched within epithelial tissues. They are unique in their Major Histocompatibility Complex-independent antigen recognition via the γδ T-cell receptor (TCR) as well as via innate receptors, making them ideal1 candidates for allogeneic “off-the-shelf” cell therapy products. In humans, two main structural subsets of γδ T cells—Vδ1 and Vδ2—have been defined, which differ in TCRδ chains, effector function, and tissue localizations. Vδ2 T cells constitute the majority of γδ T cells in peripheral blood and can be expanded with aminobisphosphonates such as zoledronic acid. In recent years, the potent antitumor functions of Vδ1 T cells have also been recognized, and new expansion protocols are being developed. Given the ample preclinical evidence of γδ T-cell efficacy against hematological malignancies, several γδ T-cell-based cell therapy products are currently in clinical development, and there has been an exponential increase in the number of adoptive γδ T-cell therapy clinical trials. This comprehensive review provides an overview of the rationale for γδ T-cell therapy, ongoing clinical trials, as well as the challenges and future role of γδ T-cell-based immune therapies in hematology
Enhanced YOLOv8 with DWR-DRB and SPD-Conv for mechanical wear fault diagnosis in aero-engines
No full textAero-engines, as complex systems integrating numerous rotating components and accessory equipment, operate under harsh and demanding conditions. Prolonged use often leads to frequent mechanical wear and surface defects on accessory parts, which significantly compromise the engine’s normal and stable performance. Therefore, accurately and rigorously identifying failure modes is of critical importance. In this study, failure modes are categorized into notches, scuffs, and scratches based on original bearing structure images. The YOLOv8 architecture is adopted as the base framework, and a Dilated Reparameterization Block (DRB) is introduced to enhance the Dilation-Wise Residual (DWR) module. This structure uses a large convolutional kernel to capture fragmented and sparse features in wear images, ensuring a wide receptive field. The concept of structural reparameterization is incorporated into DWR to improve its ability to capture detailed target information. Additionally, the standard convolutional layer in the head of the improved DWR-DRB structure is replaced by Spatial-Depth Convolution (SPD-Conv) to reduce the loss of wear morphology and enhance the accuracy of fault feature extraction. Finally, a fusion structure combining Focaler and MPDIoU is integrated into the loss function to leverage their strengths in handling imbalanced classification and bounding box geometric regression. The proposed method achieves effective recognition and diagnosis of mechanical wear fault patterns. The experimental results demonstrate that, compared to the baseline YOLOv8, the proposed method improves the mAP50 for fault diagnosis and recognition from 85.4% to 91%
SCORCH2: a generalised heterogeneous consensus model for high-enrichment interaction-based virtual screening
No full textThe discovery of effective therapeutics remains a complex, costly, and time-consuming endeavor, characterized by high failure rates and significant resource investments. A central bottleneck in early-stage drug discovery is identifying suitable hit compounds with moderate affinity for known biological targets. Although advancements occur, current in silico virtual screening methods are subject to limitations, including model overfitting, data bias, and constrained interpretability in their predictive processes. In this study, we present SCORCH2, a machine learning-based framework designed to simultaneously enhance the performance and interpretability of virtual screening by leveraging interaction features. Comparing with its predecessor SCORCH, SCORCH2 exhibits superior predictive accuracy and generalizability across a wide range of biological targets. Importantly, SCORCH2 demonstrates robust hit identification capabilities on previously unseen targets, indicating strong transferability. Furthermore, SCORCH2 obviates the need for meticulous docking pose selection, streamlining the screening process. These advances highlight the potential of SCORCH2 as a valuable tool in accelerating drug discovery campaigns
Health risk realization versus warning: Impact on lifestyle behaviours
No full textUsing individual-level panel data from Understanding Society I estimate the response to a health risk realization on a healthy lifestyle index. To overcome the endogeneity of a diagnosis, I match on initial health risks. I find individuals improve their overall lifestyle healthiness when faced with a large negative health event such as a heart attack or diabetes diagnosis, interpreted as a precise signal about their health status, whereas they do not respond to a noisier signal through solely receiving information about certain health risk factors, such as a diagnosis of high blood pressure or angina (chest pain). The drivers of the overall effect are a decrease in the number of cigarettes smoked and an increase in not drinking alcohol; there is no significant effect found for either diet or exercise. I find some heterogeneity by sex, but only when looking at individual lifestyle behaviours. Overall, the findings suggest that the realization of a health risk leads individuals to improve their lifestyle behaviours, while only a noisier signal about their health risks leads to no such change
Navitoclax acts synergistically with irradiation to induce apoptosis in preclinical models of H3K27M-altered diffuse midline glioma
No full textDiffuse midline gliomas (DMGs) with histone H3K27M mutations represent a devastating paediatric brain cancer characterised by abysmal prognosis and limited treatment options. The only approved treatment is radiotherapy (RT), but most of the tumours relapse with fatal consequences. The effects of RT remain unknown because patients are not biopsied during treatment. Here, we sought to investigate whether irradiation leads to senescence induction in DMG and explore the efficacy of senolytics. We show that ionising radiation induces senescence in various H3K27M-altered DMG cell lines. Senescence induction is demonstrated by immunocytochemistry, RNA-sequencing and analysis of SASP factors by ELISA. Through testing several senolytic compounds, we identify that Bcl2 family inhibitors (e.g., Navitoclax) act as potent senolytics, driving senescent DMG cells into apoptosis,
primarily via Bcl-xL inhibition. Reinforcing these findings, proteolysis-targeting chimeras (PROTACs) targeting Bcl-xL and galacto-conjugated Navitoclax (Nav-Gal) also exhibit strong senolytic activity against senescent DMG cancer cells. Finally, we show that a combination of irradiation with Navitoclax enhances cancer cell apoptosis in an orthotopic xenograft DMG model. Together, the data demonstrate that ionising irradiation leads to senescence induction in H3K27M-altered human DMG cell lines, making them particularly sensitive to apoptosis
through Bcl-xL inhibition
[Fe(phen)₃]²+ and [Fe(phen)₃]²+-loaded nanostructured lipid system: in silico, in vitro, and in vivo efficacy against Mycobacterium tuberculosis
No full textTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the leading causes of mortality from infectious diseases worldwide. So, this study investigates the antimicrobial potential of [Fe(phen)3]2+ (FEP) and FEP-loaded nanostructured lipid systems (NLS@FEP) as an innovative therapeutic approach for TB. The FEP showed promising antimycobacterial activity in simulated physiological environments, with minimum inhibitory concentrations (MIC90) from 3.92 to 0.98 μg mL–1. FEP combination with rifampicin or pretomanid significantly reduced the MIC90, with fractional inhibitory concentration index (FICI) of 0.27 and 0.103, respectively. Field emission scanning electron microscopy (FE-SEM) analysis revealed significant structural alterations in the Mtb cell wall, suggesting that FEP interferes with its synthesis. In silico analyses and whole-genome sequencing (WGS) supported these findings, identifying mutations in key genes, such as ponA1, which encodes a penicillin-binding protein involved in peptidoglycan synthesis. In silico modeling predicted high FEP affinity for PonA1, in line with FE-SEM observations; however, these predictions are hypothesis-generating and require functional validation. FEP-loaded nanostructured lipid system (NLS@FEP) was designed to optimize FEP activity, which improved its stability and bioavailability. In a murine model infected with Mtb H37Rv, free FEP and NLS@FEP achieved complete elimination of pulmonary infection
Previous tuberculosis modifies spirometry outcomes among small-scale gemstone miners in Tanzania: a cross-sectional, clinic-based study
No full textIntroduction
Small-scale miners are known to experience high silica exposures, associated with high rates of silicosis and Tuberculosis (TB). TB has been shown to worsen underlying impairment of lung function in miners. We describe the spirometry outcomes, according to previous TB status, among a large cohort of small-scale miners attending a screening centre.
Methods
We collected cross-sectional spirometry and clinical data from consecutive miners and ex-miners, with negative Xpert TB results, attending a screening clinic in Northern Tanzania, between February 2018 and December 2020. Spirometry values assessed using the ATS/ERS 2019 quality criteria and compared to GLI 2022 global (GLIgl) reference values. We used multiple linear regression to model excess Forced Expiratory Volume in 1 second (FEV1) and Forced Vital Capacity (FVC) loss using
16 an a priori interaction between duration of work and previous TB.
Results
Of 542 participants, 80 (15%) reported previous TB. At least moderate (z-score ≤−2.5) FEV1 reductions were present in 51% of participants with previous TB and 18% of those without previous TB. For FVC, respective values were 34% and 10%. A miner with TB and 10 years of work was modelled to have lost 1405 (95% CI 1134, 1676) mls of FEV1 and 1342 (95% CI 1042, 1641) mls of FVC compared to GLIgl reference values. For miners without previous TB, the corresponding excess FEV1 and FVC losses were 693 (95% CI 581, 804) mls and 624 (95% CI 504, 743) mls, respectively.
Discussion
Unmeasured silicosis may partially explain some of the observed effect of previous TB. However, this does not change our observation of a clinically significant burden
of abnormal spirometry in a clinic-based population of small-scale miners. Reducing silica-exposures and preventing TB are key to improving lung health in miners
Safeguarding maternal health against extreme heat in India: a policy analysis of state‐level heat action plans
No full textObjective
This study identifies and characterizes policy measures across Indian states to protect pregnant and lactating women from extreme heat exposure through a thematic analysis of state-level heat and climate adaptation plans.
Methods
Using content analysis, we systematically reviewed publicly available Heat Action Plans (HAPs) (N = 19) and, when unavailable, the State Action Plan on Climate Change (N = 16) from all Indian states and union territories. Strategies referencing pregnant and lactating women, either directly or indirectly (i.e., as part of a group identified as vulnerable), were extracted, categorized and coded.
Results
Twelve of 35 state plans (33%) contained no recommendations for pregnant or lactating women. The remaining 23 plans listed 214 strategies, comprising 102 unique strategies (no repetitions). However, only 40 directly addressed this group. Karnataka (16), Telangana (11), and Delhi (10) had the highest number of unique strategies. Strategies were categorized using the four-category climate adaptation framework of Chersich et al. and fell into behavior change actions (n = 100), structural/policy, and climate-financing support measures (n = 51), health system interventions (n = 38), and built environment/cooling solutions (n = 25).
Conclusion
Strategies specifically addressing pregnant and lactating women during extreme heat remain limited across Indian states, with most focusing on behavioral interventions rather than structural solutions. Critical gaps exist in 12 states with no targeted measures. Very few strategies focus on pregnant and lactating women in the HAPs. Strengthening evidence-based, targeted adaptation policies and implementing comprehensive structural interventions are critical to protecting them from the increasing heat exposure risks