Chimeric antigen receptor T (CAR-T) cell therapy achieved extraordinary achievements results in antitumor treatments, especially against hematological malignancies, where it leads to remarkable, ...long-term antineoplastic effects with higher target specificity. Nevertheless, some limitations persist in autologous CAR-T cell therapy, such as high costs, long manufacturing periods, and restricted cell sources. The development of a universal CAR-T (UCAR-T) cell therapy is an attractive breakthrough point that may overcome most of these drawbacks. Here, we review the progress and challenges in CAR-T cell therapy, especially focusing on comprehensive comparison in UCAR-T cell therapy to original CAR-T cell therapy. Furthermore, we summarize the developments and concerns about the safety and efficiency of UCAR-T cell therapy. Finally, we address other immune cells, which might be promising candidates as a complement for UCAR-T cells. Through a detailed overview, we describe the current landscape and explore the prospect of UCAR-T cell therapy.
We collected street dust from Huainan, a typical coal-mining city in China, to investigate the contamination features and health risks of heavy metals. Concentrations of Co, Cr, Cu, Pb, As, and Sb ...were generally low to moderate, while pollution levels of Cd and Hg were moderate to high. Concentrations of Cd and Hg were associated with considerable health risks at 64.3% and 58.6% of sites, respectively. In particular, about a fifth of samples had associated high risks as a result of Hg contamination levels. Relative to other urban areas, the street dust from the mining area had no more severe metal pollution, which might be partly attributed to the deposition of coal dust onto street dusts. A source assessment indicated that metals in dust form Huainan were mainly derived from vehicular-related activities, industrial emissions, weathering of coal dust and natural soils, and coal combustion. Although the health risk levels from exposure to individual metals in dusts were low, the non-carcinogenic risks from multiple metals to local children exceeded the acceptable level (1.0), suggesting that the overall risk from exposure to multiple metals in dust is concerning.
•Metal concentrations in street dusts from a coal-mining city were investigated.•Pollution levels of Cd and Hg were moderate to high.•Metal pollution in dust from the mining area was no more severe than urban areas.•The overall risk from multiple metals in dusts to local children is unacceptable.
Air pollution poses a significant health risk to the human population, especially for vulnerable groups such as the elderly, potentially discouraging their engagement in physical activity. However, ...there is a lack of sufficient objective and longitudinal data in current research on how air pollution affects physical activity among older adults. With these gaps, we aimed to explore the relationship between air pollution and objective measurement-based physical activity among older adults by engaging in a longitudinal study design.
A total of 184 older adults were recruited from three cities with varying levels of air quality. Mean daily minutes of physical activity were measured with 7 consecutive days of accelerometer monitoring (ActiGraph GT3X-BT). Corresponding air pollution data including daily PM
(µg/m
), PM
(µg/m
) and air quality index (AQI) were sourced from the China National Environmental Monitoring Centre at monitor locations close to older adults' addresses. Associations between air quality and physical activity were estimated using a fixed effect model, adjusting for average daytime temperature, rain, age and weight.
AQI and PM
were observed to exhibit significant, inverse, and linear associations with mean daily walk steps, minutes of light physical activity (LPA), moderate physical activity (MPA) and moderate-to-vigorous physical activity (MVPA) in the single variable models. A one-level increase in AQI corresponded to a decline in 550.04 steps (95% CI = -858.97, -241.10; p < 0.001), 10.43 min (95% CI = -17.07, -3.79; p < 0.001), 4.03 min (95% CI = -7.48, -0.59; p < 0.001) and 4.16 min (95% CI = -7.77, -0.56; p < 0.001) in daily walking steps, LPA, MPA, and MVPA, respectively. A one-level increase in PM
correlated with a decline in daily walk steps, LPA, MPA and MVPA by 361.85 steps (95% CI = -516.53, -207.16; p < 0.001), 8.97 min (95% CI = -12.28, -5.66; p < 0.001), 3.73 min (95% CI = -5.46, -2.01; p < 0.001,) and 3.79 min (95% CI = -5.59, -1.98; p < 0.001), respectively. However, PM
displayed a significant negative association exclusively with LPA, with one-level increase in PM
resulting in a 3.7-minute reduction in LPA (95% CI = -6.81, -0.59, p < 0.05).
Air pollution demonstrates an inverse association with physical activity levels among older adults, potentially discouraging their engagement in physical activity. Different air quality indicators may exert varying impacts on physical activity. Future studies are warranted to enhance policy interventions aimed at reducing air pollution and promoting physical activity.
The effects of grilling on health risks posed by polycyclic aromatic hydrocarbons (PAHs) in food remain poorly understood. The changes of concentrations, distributions, and risks of PAHs in ...vegetables and animal-based foods before and after grilling were investigated in this study. The sum of 16 (∑16) PAH concentrations in grilled vegetables and grilled animal-based foods were 60.4–1936 and 69.1–4668 ng/g, respectively. Grilling markedly increased the ∑16 PAH concentrations in most foods analyzed. Grilling clearly increased the low-molecular-weight PAH contributions to the ∑16 PAH concentrations in vegetables but increased the heavier PAH contributions to the ∑16 PAH concentrations in some animal-based foods. With the grilling, the total benzoapyrene-equivalent concentrations of the 16 PAHs in Chinese chives and enoki mushrooms and most animal-based foods were improved significantly. Source assessments indicated that environmental sources contributed PAHs to the raw foods and high-temperature pyrolysis during grilling contributed large proportions of the PAHs in the grilled foods. The carcinogenic risks to humans from the exposure of PAHs in vegetables and animal-based foods were estimated. Grilling increased the total risks of PAHs in vegetables and animal-based foods by factors of 3.12 and 5.49, respectively. Total risks of PAHs in the 11 foods were 3.43 times higher when the foods were grilled than when raw. The results suggested that the negative effects of grilling on human health should be of great concern.
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•Effects of grilling on the risks posed by PAHs in food were investigated.•Pyrolysis during grilling contributes large amounts of PAHs to cooked food.•Grilling increased the risk posed by PAHs in vegetables by a factor of 3.12.•Grilling increased the risk from PAHs in animal-based foods by a factor of 5.49.
Mitochondrial proton leak is the principal mechanism that incompletely couples substrate oxygen to ATP generation. This chapter briefly addresses the recent progress made in understanding the role of ...proton leak in the pathogenesis of cardiovascular diseases. Majority of the proton conductance is mediated by uncoupling proteins (UCPs) located in the mitochondrial inner membrane. It is evident that the proton leak and reactive oxygen species (ROS) generated from electron transport chain (ETC) in mitochondria are linked to each other. Increased ROS production has been shown to induce proton conductance, and in return, increased proton conductance suppresses ROS production, suggesting the existence of a positive feedback loop that protects the biological systems from detrimental effects of augmented oxidative stress. There is mounting evidence attributing to proton leak and uncoupling proteins a crucial role in the pathogenesis of cardiovascular disease. We can surmise the role of "uncoupling" in cardiovascular disorders as follows; First, the magnitude of the proton leak and the mechanism involved in mediating the proton leak determine whether there is a protective effect against ischemia-reperfusion (IR) injury. Second, uncoupling by UCP2 preserves vascular function in diet-induced obese mice as well as in diabetes. Third, etiology determines whether the proton conductance is altered or not during hypertension. And fourth, proton leak regulates ATP synthesis-uncoupled mitochondrial ROS generation, which determines pathological activation of endothelial cells for recruitment of inflammatory cells. Continue effort in improving our understanding in the role of proton leak in the pathogenesis of cardiovascular and metabolic diseases would lead to identification of novel therapeutic targets for treatment.
Taking advantage of the immune system to exert an antitumor effect is currently a novel approach in cancer therapy. Adoptive transfer of T cells engineered to express chimeric antigen receptors ...(CARs) targeting a desired antigen has shown extraordinary antitumor activity, especially in refractory and relapsed B-cell malignancies. The most representative in this respect, as well as the most successful example, is CD19 CAR T-cell therapy in B-cell acute lymphoblastic leukemia (B-ALL). However, with the widespread use of CAR T-cell therapy, problems of resistance and relapse are starting to be considered. This review provides a comprehensive picture of the mechanisms of resistance to CAR T-cell therapy from three aspects, namely, CAR T-cell factors, tumor factors, and tumor microenvironment factors, offering insights for improving CAR T-cell therapy.
Clothing may be a potential contributor to body metal burden in children. However, available information on heavy metals in children’s clothing is extremely limited and the associated health risks ...remain poorly understood. This study investigated the concentrations of Pb, Cd, Co, Zn, Cr, As, Cu and Ni in new preschool children’s clothing manufactured in four Asian regions. The children’s clothing had higher levels of Ni and Cr but lower levels of Pb and Cd in comparison to the concentrations reported in other textile products. The concentrations of Cd were higher in the black clothing than those in the white and color samples. The non-cotton samples contained higher Co concentrations. The Pb concentrations in the samples manufactured in China were significantly higher than those in the other three regions. We estimated the dermal exposure doses for these metals and calculated the associated risks. The results indicated that the health risks from exposure to these metals in the children’s clothing were acceptable. However, more research is required to investigate heavy metals and the associated risks in child clothing due to the increasing complexity of their materials and manufacturing processes.
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•Eight metals in children’s clothing from four Asian regions were measured.•The investigated metals were prevalent in the preschool children’s clothing.•Metal concentrations differed by material type, color, and manufacturing region.•The health risks from exposure to metals via clothing were acceptable.
•Soil metal pollution with different e-waste recycling activities was determined.•In general, the soils were contaminated heavily with Cd, Cu, Pb and Sb.•Levels of Pb, Cr, Sb, Cd and Hg in the ...abandoned site were relatively lower.•Metal levels in the sites of acid leaching, dismantling, and burning, were high.
Heavy metal pollution of the environment caused by e-waste recycling is of increasing concern, but little information is available on metal emissions during e-waste processing activities. Here, the concentrations of nine metals in soil at four contaminated sites in Qingyuan (an e-waste recycling area in China) and the risks posed were investigated. Soil at the sites was polluted with metals, particularly Cd, Cu, Pb, and Sb, the concentrations of which were 2.83–2306, 2.17–1880, 0.96–1971, and 9.28–5607 times higher, respectively, than local background concentrations. The Cd, Cr, Hg, Pb, and Sb concentrations were significantly lower in soil at an abandoned site than at acid-leaching, dismantling, and burning sites. The risks posed by metals in soil to human and environmental health were much higher at the acid-leaching and burning sites than the dismantling and abandoned sites. Source assessments indicated the differences in metal concentrations at the different sites were caused by different e-waste recycling activities at the sites. The results indicated crude e-waste processing is an important source of heavy metals to soil and should be of great concern. Pollution control measures and risk management strategies specific to soil contaminated through e-waste processing activities should be developed.
Dazomet is a dry powder formulation that releases toxic gas containing methyl isothiocyanate, which controls soil-borne pests and weeds, improving crop yields when applied to moist soils. To explore ...the efficacy of dazomet fumigation in the cultivation of the perennial herb Codonopsis pilosula, four typical cultivars (G1, G2, W1 and TCK) in Gansu Province were selected for seedling cultivation after soil fumigation (F) by dazomet, and non-fumigated soil was used as a control (CK). The experiments took 2 years to complete. The functional diversity of the soil enzymes and microorganisms, seedling emergence and physiological characteristics, and the quality and yield of Codonopsis seedlings and Radix were assessed. The results showed that the seed emergence rate, seedling re-green rate and several antioxidant enzymatic activities improved in the treatments involving soil fumigation with dazomet, and membrane lipid peroxidation in the seedlings decreased. On average, compared with those of the respective controls, the root viability and yield of the seedlings of the tested cultivars also increased by 34.87% and 42.4%, respectively, and the incidence of root rot in the seedlings was reduced by 83.9%, compared with their respective controls. After harvest, the yield increased by 23.9%, the incidence of root rot decreased by 61.3%, increase in yield and a 61.3% reduction in incidence, and the medicinal materials were determined to be safe and residue-free. The effects of fumigation were cultivar-specific and were especially prominent in G2. Therefore, soil fumigation with dazomet could improve the quality and productivity of Codonopsis pilosula seedlings. Taken together, these findings suggest that when herbs are bred by seedling transplantation, especially cultivars of good quality but poor resistance or species with rare germplasm resources, soil fumigation provides a way to improve cultivation effectiveness and, more importantly, ensures the probability of successfully breeding the species.
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