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Tumour immunotherapy holds great promise as a treatment for cancer, which ranks as the second highest cause of mortality worldwide. This therapeutic approach can be broadly categorized into two main types: active immunotherapy and passive or adoptive immunotherapy. Active immunotherapy, such as cancer vaccines, stimulates the patients’ immune system to target tumour cells. On the other hand, adoptive immunotherapy involves supplying in vitro activated immune cells, such as T cells, natural killer cells and macrophages, to the patient to combat the tumour. Induced pluripotent stem cells are extensively utilized in both active and adoptive tumour immunotherapy due to their pluripotency and ease of gene editing. They can be differentiated into various types of immune cells for direct cancer treatment and can also function as tumour vaccines to elicit an immune response against the tumour. Importantly, iPSCs can be leveraged to develop off-the-shelf allogenic immunotherapy products.
Conclusion
This article provides a comprehensive review of the application of iPSCs in tumor immunotherapy, along with a discussion of the opportunities and challenges in this evolving field.
A dual-band dual-polarized wearable antenna that applies to two different operating modes of wireless body area networks is proposed in this letter. The antenna radiates simultaneously in the ISM band at 2.45 and 5.8 GHz. It consists of a rigid button-like radiator and a flexible fabric radiator. At 2.45 GHz, an omnidirectional circularly polarized pattern is radiated by the flexible radiator, which is suitable for the on-body communication. At the same time, a linearly polarized broadside pattern for off-body communication is generated by button radiator at 5.8 GHz. The antenna has been validated in free space and human body environments. The impedance bandwidth at 2.45 and 5.8 GHz are 5% and 35%, and the gain is measured to be 0.15 and 5.95 dBi, respectively. Furthermore, the specific absorption rates are simulated. At 2.45 and 5.8 GHz, the results averaged over 1 g of body tissue are 0.128 and 0.055 W/kg. The maximum value at both bands is below the IEEE C95.3 standard of 1.6 W/kg.
The heating effect of electromagnetic waves in ion cyclotron range of frequencies (ICRFs) in magnetic confinement fusion device is different in different plasma conditions. In order to evaluate the ICRF heating effect in different plasma conditions, we conducted a series of experiments and corresponding TRANSP simulations on the EAST tokamak. Both simulation and experimental results show that the effect of ICRF heating is poor at low core electron density. The decrease in electron density changes the left-handed electric field near the resonant layer, resulting in a significant decrease in the power absorbed by the hydrogen fundamental resonance. However, quite a few experiments must be performed in plasma conditions with low electron density. It is necessary to study how to make ICRF heating best in low electron density plasma. Through a series of simulation scans of the parallel refractive index (n//) of the ICRF antenna, it is concluded that the change of the ICRF antenna n// will lead to the change of the left-handed electric field, which will change the fundamental absorption of ICRF power by the hydrogen minority ions. Fully considering the coupling of ion cyclotron wave at the tokamak boundary and the absorption in the plasma core, optimizing the ICRF antenna structure and selecting appropriate parameters such as parallel refractive index, minority ion concentration, resonance layer position, plasma current and core electron temperature can ensure better heating effect in the ICRF heating experiments in the future EAST upgrade. These results have important implications for the enhancement of the auxiliary heating effect of EAST and other tokamaks.
The Chinese pangolin Manis pentadactyla is categorized as Critically Endangered on the IUCN Red List, but the development of effective conservation strategies is hindered by a lack of data on its distribution range and population dynamics. In addition, standardized survey and analysis methods are required to facilitate the sharing of results and maximize conservation effectiveness. To fill these knowledge and methodological gaps, we investigated the occurrence of pangolin burrows in the subtropical forest ecosystem of Fujian, China. We surveyed a total of 70 transects across five land-cover types within the Fujian Junzifeng National Nature Reserve and detected 87 burrows. The majority of burrows (87%) were located in mixed conifer and broadleaf forests. We used six environmental variables in a generalized linear model to examine the relationship between the occurrence of burrows and environmental factors. The average model results from the best model set showed that the distribution of burrows was significantly influenced by forest type. For effective pangolin conservation, we recommend that local conservation authorities prioritize the protection of mixed conifer and broadleaf forests. Our findings support the local conservation of the Chinese pangolin and the standardization of surveys and conservation efforts across the species’ range.
Dot array deposition through electrohydrodynamic (EHD) printing is widely used for high resolution and material utilization advantages. However, the conventional printing method is subject to a printing frequency limit known as the capillary frequency of the meniscus oscillation, where the jet directly contacts the substrate. This makes the printing frequency of EHD printing maintain at a low level and that is difficult to improve. In this work, a method for high-frequency EHD printing through continuous pinch-off is proposed. The characteristic frequency is broken through. A model is established to reveal the printing mechanism by combining the Poisson–Nernst–Planck equation and the phase field method. The unreal charge leakage is prevented by constructing a transition function for the fluid’s properties. The stability of the Taylor cone’s deformation and the droplets’ generation is studied. The measurement criterion for printing frequency is determined. The suitable printing height that can prevent the jet from directly contacting the substrate is obtained by investigating its influence on the printing states and frequency. The phase diagram considering the liquid’s conductivity and viscosity is presented to distinguish whether the printing is based on the end-pinching or Rayleigh–Plateau instability. The influence of the conductivity, viscosity, flow rate and printing voltage on the printing frequencies is studied quantitatively. Finally, scaling laws for printing frequency are proposed by theoretical analyses and summarizing the numerical data. This work could be beneficial for further enhancing the printing frequency of EHD printing.
Human milk oligosaccharides offer unique benefits for infant growth and development. Buffalo milk, characterized by a mild flavor and high nutritional value, has attracted considerable interest. To characterize the oligosaccharide profile and composition of buffalo milk, we conducted qualitative and quantitative analysis of milk oligosaccharides at the early- and late-lactation stages of crossbred (Nili-Ravi × Murrah × local) buffaloes from Guangxi, China. The results revealed a total of 97 oligosaccharides including 17 novel oligosaccharides, with concentrations of 416.6 ± 25.86 and 368.3 ± 10.29 mg/L in milk from early- and late-lactation stages, respectively. The most abundant oligosaccharides were 3’-sialyllactose (3’-SL), difucosyllactose (DFL), 6’-sialyllactose (6’-SL), and a newly discovered compound, 2142. The oligosaccharides in crossbred (Nili-Ravi × Murrah × local) buffaloes demonstrated greater diversity than those found in the milk of other dairy animals, highlighting its potential as a high-quality nutritional resource for adults and infants.
Megacities around the world are increasingly confronted with conservation and restoration bottlenecks due to the competing demands of urban expansion and environmental conservation. This study investigates conservation prioritization strategies for balancing biodiversity protection, ecosystem service (ES) supply and landscape connectivity in rapidly urbanizing Beijing. By employing spatially explicit modelling and prioritization scenario techniques, we identify spatially heterogeneous priority zones. We demonstrate that high-value areas for ES supply, particularly carbon storage and water regulation, concentrate primarily in Beijing’s north-western mountainous regions, covering c. 62% of the city’s area. Conversely, critical habitats for threatened species and key connectivity corridors are dispersed, with 22.89% of critical habitats located within urban built-up areas. Gap analysis reveals limited alignment between Beijing’s current ecological security patterns, with only 9.6% coverage of the identified top 10% conservation priority zones, especially within the metropolitan core. The study underscores significant trade-offs among different ecological objectives and multi-criteria conservation strategies. We propose an optimized conservation framework based on zonation analysis to guide targeted landscape planning decisions. This approach provides actionable insights for urban policymakers to achieve comprehensive sustainability, emphasizing the importance of protecting critical ecological areas in both urban and rural landscapes amid ongoing urban expansion.
This research employs an enhanced Polar Operation Limit Assessment Risk Indexing System (POLARIS) and multi-scale empirical analysis methods to quantitatively evaluate the risks in icy region navigation. It emphasises the significant influence of spatial effects and external environmental factors on maritime accidents. Findings reveal that geographical location, environmental and ice conditions are crucial contributors to accidents. The models indicate that an increase in ports, traffic volume and sea ice density directly correlates with higher accident rates. Additionally, a novel risk estimation model is introduced, offering a more accurate and conservative assessment than current standards. This research enriches the understanding of maritime accidents in icy regions, and provides a robust framework for different navigation stages and conditions. The proposed strategies and model can effectively assist shipping companies in route planning and risk management to enhance maritime safety in icy regions.
Haemonchus contortus is a parasitic nematode that causes significant economic losses in ruminant livestock worldwide. In this study, we assessed the global genetic diversity and population structure of H. contortus using mitochondrial COX1 and ribosomal ITS2 sequences retrieved from the NCBI GenBank database. In total, 324 haplotypes of the COX1 and 72 haplotypes of the ITS2 were identified. The haplotype diversity values were all higher than 0.5, and the nucleotide diversity values were higher than 0.005. The Tajima’s D value for COX1 (−1.65634) was higher than that for ITS2 (−2.60400). Fu’s Fs, Fu and Li’s D (FLD), and Fu and Li’s F (FLF) values also showed high negative values, indicating a high probability of future population growth. In addition, the high fixation index (FST) value suggests significant genetic differentiation among populations. The haplotype networks of H. contortus populations based on COX1 sequences revealed clear geographic clustering, whereas ITS2 sequences showed more haplotype admixture across regions. The results of phylogenetic analyses were consistent with the haplotype networks. These findings highlighted that H. contortus populations exhibit significant genetic variation and are undergoing rapid population expansion, with clear genetic differences across geographic regions. This study established critical baseline data for future molecular epidemiology studies, which could guide region-specific parasite surveillance and targeted control strategies, thus helping to mitigate the risk of cross-border parasite transmission and drug resistance.
This study aimed to examine the relationship between FGF19 and depressive symptoms, measured by BDI scores and investigate the moderating role of smoking.
Methods:
This study involved 156 Chinese adult males (78 smokers and 78 non-smokers) from September 2014 to January 2016. The severity of depressive symptoms was evaluated using the BDI scores. Spearman rank correlation analyses were used to investigate the relationship between CSF FGF19 levels and BDI scores. Additionally, moderation and simple slope analyses were applied to assess the moderating effect of smoking on the relationship between the two.
Results:
FGF19 levels were significantly associated with BDI scores across all participants (r = 0.26, p < 0.001). Smokers had higher CSF FGF19 levels and BDI scores compared to non-smokers (445.9 ± 272.7 pg/ml vs 229.6 ± 162.7 pg/ml, p < 0.001; 2.7 ± 3.0 vs 1.3 ± 2.4, p < 0.001). CSF FGF19 levels were positively associated with BDI scores in non-smokers (r = 0.27, p = 0.015), but no similar association was found among smokers (r = -0.11, p = 0.32). Linear regression revealed a positive correlation between FGF19 and BDI scores (β = 0.173, t = 2.161, 95% CI: 0.015- 0.331, p < 0.05), which was negatively impacted by smoking (β = -0.873, t = -4.644, 95% CI: -1.244 to -0.501, p < 0.001).
Conclusion:
These results highlight the potential role of FGF19 in individuals at risk for presence of or further development of depressive symptoms and underscore the importance of considering smoking status when examining this association.
Overnutrition during before and pregnancy can cause maternal obesity and raise the risk of maternal metabolic diseases during pregnancy, and in offspring. Lentinus edodes may prevent or reduce obesity. This study aimed to to assess Lentinus edodes fermented products effects on insulin sensitivity, glucose and lipid metabolism in maternal and offspring, and explore its action mechanism. A model of overnutrition during pregnancy and lactation was developed using a 60 % kcal high-fat diet in C57BL6/J female mice. Fermented Lentinus edodes (FLE) was added to the diet at concentrations of 1 %, 3 %, and 5 %. The results demonstrated that FLE to the gestation diet significantly reduced serum insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) in pregnant mice. FLE can regulate maternal lipid metabolism and reduce fat deposition. Meanwhile, the hepatic phosphoinositide-3-kinase-protein kinase (PI3K/AKT) signaling pathway was significantly activated in the maternal mice. There is a significant negative correlation between maternal FLE supplementation doses and offspring body fat percentage and visceral fat content. Furthermore, FLE supplementation significantly increased offspring weaning litter weight, significantly reduced fasting glucose level, serum insulin level, HOMA-IR and serum glucose level, significantly activated liver PI3K/AKT signaling pathway in offspring, and upregulated the expression of liver lipolytic genes adipose triglyceride lipase, hormone-sensitive lipase and carnitine palmitoyltransferase 1 mRNA. Overall, FLE supplementation can regulate maternal lipid metabolism and reduce fat deposition during pregnancy and lactation, and it may improve insulin sensitivity in pregnant mothers and offspring at weaning through activation of the PI3K/AKT signaling pathway.
The extracellular matrices, such as the haemolymph, in insects are at the centre of most physiological processes and are protected from oxidative stress by the extracellular antioxidant enzymes. In this study, we identified two secreted superoxide dismutase genes (PxSOD3 and PxSOD5) and investigated the oxidative stress induced by chlorpyrifos (CPF) in the aquatic insect Protohermes xanthodes (Megaloptera: Corydalidae). PxSOD3 and PxSOD5 contain the signal peptides at the N-terminus. Structure analysis revealed that PxSOD3 and PxSOD5 contain the conserved CuZn-SOD domain, which is mainly composed of β-sheets and has conserved copper and zinc binding sites. Both PxSOD3 and PxSOD5 are predicted to be soluble proteins located in the extracellular space. After exposure to different concentrations of sublethal CPF, MDA content in P. xanthodes larvae were increased in a dose-dependent manner; SOD and CAT activities were also higher in CPF-treated groups than that in the no CPF control, indicating that sublethal CPF induces oxidative stress in P. xanthodes larvae. Furthermore, PxSOD3 and PxSOD5 expression levels and haemolymph SOD activity in the larvae were downregulated by sublethal CPF at different concentrations. Our results suggest that the PxSOD3 and PxSOD5 are putative extracellular antioxidant enzymes that may play a role in maintaining the oxidative balance in the extracellular space. Sublethal CPF may induce oxidative stress in the extracellular space of P. xanthodes by reducing the gene expression and catalytic activity of extracellular SODs.
Parental psychopathology is a known risk factor for child autistic-like traits. However, symptom-level associations and underlying mechanisms are poorly understood.
Methods
We utilized network analyses and cross-lagged panel models to investigate the specific parental psychopathology related to child autistic-like traits among 8,571 adolescents (mean age, 9.5 years at baseline), using baseline and 2-year follow-up data from the Adolescent Brain Cognitive Development study. Parental psychopathology was measured by the Adult Self Report, and child autistic-like traits were measured by three methods: the Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5 autism spectrum disorder (ASD) subscale, the Child Behavior Checklist ASD subscale, and the Social Responsiveness Scale. We also examined the mediating roles of family conflict and children’s functional brain connectivity at baseline.
Results
Parental attention-deficit/hyperactivity problems were central symptoms and had a direct and the strongest link with child autistic-like traits in network models using baseline data. In longitudinal analyses, parental attention-deficit/hyperactivity problems at baseline were the only significant symptoms associated with child autistic-like traits at 2-year follow-up (β = 0.014, 95% confidence interval [0.010, 0.018], FDR q = 0.005), even accounting for children’s comorbid behavioral problems. The observed association was significantly mediated by family conflict (proportion mediated = 11.5%, p for indirect effect <0.001) and functional connectivity between the default mode and dorsal attention networks (proportion mediated = 0.7%, p for indirect effect = 0.047).
Conclusions
Parental attention-deficit/hyperactivity problems were associated with elevated autistic-like traits in offspring during adolescence.
Rare earth elements (REEs) preserved in speleothems have garnered increasing attention as ideal proxies for the paleoenvironmental reconstruction. However, due to their typically low contents in stalagmites, the availability of stalagmite-based REE records remains limited. Here we present high-resolution REEs alongside oxygen isotope (δ18O) records in stalagmite SX15a from Sanxing Cave, southwestern China (110.1–103.3 ka). This study demonstrates that REE records could provide useful information for the provenance and formation process of the stalagmite, due to consistent distribution pattern across different periods indicating stable provenance. More interestingly, the total REE (ΣREE) record could serve as an effective indicator to reflect local hydrological processes associated with monsoonal precipitation. During Marine Isotopic Stage (MIS) 5d, a relatively low ΣREE content is consistent with the positive SX15a δ18O and negative NGRIP δ18O, reflecting a dry-cold environment; while during MIS 5c, a generally high ΣREE content suggests a humid-warm circumstance. Furthermore, the ΣREE record captured four prominent sub-millennial fluctuations within the Greenland interstadial 24 event, implying a combined influence by the regional climate and local soil redox conditions. Our findings indicate that the stalagmite-based REE records would be a useful proxy for better understanding of past climate and environment changes.
While the literature has largely focused on legal challenges to public healthcare rationing decisions, claims against private insurance companies in voluntary health insurance (VHI) schemes have received less attention. This paper aims to fill this gap by analysing a representative sample of 1,547 court of appeal decisions related to treatment funding claims filed against private insurance companies in Brazil from 2018 to 2021. Courts decided 83.6% of cases in favour of patients, ordering VHI companies to fully fund the claimed treatment. Patients´ rate of success is even higher (96%) in the cases in which insurance companies denied coverage on the grounds that the claimed treatment was not listed in the benefits package mandated by regulation. Court decisions present additional challenges to setting priorities through health technology assessment and explicit packages in the VHI sector. This has broader implications for health care equality and access in Brazil.
Clinical high risk for psychosis (CHR) is often managed with antipsychotic medications, but their effects on neurocognitive performance and clinical outcomes remain insufficiently explored. This study investigates the association between aripiprazole and olanzapine use and cognitive and clinical outcomes in CHR individuals, compared to those receiving no antipsychotic treatment.
Methods
A retrospective analysis was conducted on 127 participants from the Shanghai At Risk for Psychosis (SHARP) cohort, categorized into three groups: aripiprazole, olanzapine, and no antipsychotic treatment. Neurocognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB), while clinical symptoms were assessed through the Structured Interview for Prodromal Syndromes (SIPS) at baseline, 8 weeks, and one year.
Results
The non-medicated group demonstrated greater improvements in cognitive performance, clinical symptoms, and functional outcomes compared to the medicated groups. Among the antipsychotic groups, aripiprazole was associated with better visual learning outcomes than olanzapine. Improvements in neurocognition correlated significantly with clinical symptom relief and overall functional gains at follow-up assessments.
Conclusions
These findings suggest potential associations between antipsychotic use and cognitive outcomes in CHR populations while recognizing that observed differences may reflect baseline illness severity rather than medication effects alone. Aripiprazole may offer specific advantages over olanzapine, underscoring the importance of individualized risk-benefit evaluations in treatment planning. Randomized controlled trials are needed to establish causality.