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Abstract Redox imbalance is reported to play a pivotal role in tumorigenesis, cancer development, and drug resistance. Severe oxidative damage is a general consequence of cancer cell responses to treatment and may cause cancer cell death or severe adverse effects. To maintain their longevity, cancer cells can rescue redox balance and enter a state of resistance to anticancer drugs. Therefore, targeting redox signalling pathways has emerged as an attractive and prospective strategy for enhancing the efficacy of anticancer drugs and decreasing their adverse effects. Over the past few decades, natural products (NPs) have become an invaluable source for developing new anticancer drugs due to their high efficacy and low toxicity. Increasing evidence has demonstrated that many NPs exhibit remarkable antitumour effects, whether used alone or as adjuvants, and are emerging as effective approaches to enhance sensitivity and decrease the adverse effects of conventional cancer therapies by regulating redox balance. Among them are several novel anticancer drugs based on NPs that have entered clinical trials. In this review, we summarize the synergistic anticancer effects and related redox mechanisms of the combination of NPs with conventional anticancer drugs. We believe that NPs targeting redox regulation will represent promising novel candidates and provide prospects for cancer treatment in the future. Graphical Abstract

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) play critical roles in tumorigenesis, cancer progression, and drug resistance. Persistent activation of the ER stress system enhances the survival capacities of malignant tumor cells, including increased proliferation, invasion, and resistance to treatment. Dysregulation of ER function and the resultant stress is a common cellular response to cancer therapies and may lead to cancer cell death. Currently, growing evidence suggests that Traditional Chinese medicine (TCM), either as a monotherapy or in combination with other treatments, offers significant advantages in preventing cancer, inhibiting tumor growth, reducing surgical complications, improving drug sensitivity, and mitigating drug-induced damage. Some of these natural products have even entered clinical trials as primary or complementary anticancer agents. In this review, we summarize the anticancer effects of TCM monomers/natural products on the gastrointestinal (GI) tumors and explore their mechanisms through ER stress modulation. We believe that ongoing laboratory research and the clinical development of TCM-based cancer therapies hold considerable potential for advancing future cancer treatments.

Abstract Atmospheric methane is both a potent greenhouse gas and photochemically active, with approximately equal anthropogenic and natural sources. The addition of chlorine to the atmosphere has been proposed to mitigate global warming through methane reduction by increasing its chemical loss. However, the potential environmental impacts of such climate mitigation remain unexplored. Here, sensitivity studies are conducted to evaluate the possible effects of increasing reactive chlorine emissions on the methane budget, atmospheric composition and radiative forcing. Because of non-linear chemistry, in order to achieve a reduction in methane burden (instead of an increase), the chlorine atom burden needs to be a minimum of three times the estimated present-day burden. If the methane removal target is set to 20%, 45%, or 70% less global methane by 2050 compared to the levels in the Representative Concentration Pathway 8.5 scenario (RCP8.5), our modeling results suggest that additional chlorine fluxes of 630, 1250, and 1880 Tg Cl/year, respectively, are needed. The results show that increasing chlorine emissions also induces significant changes in other important climate forcers. Remarkably, the tropospheric ozone decrease is large enough that the magnitude of radiative forcing decrease is similar to that of methane. Adding 630, 1250, and 1880 Tg Cl/year to the RCP8.5 scenario, chosen to have the most consistent current-day trends of methane, will decrease the surface temperature by 0.2, 0.4, and 0.6 °C by 2050, respectively. The quantity and method in which the chlorine is added, its interactions with climate pathways, and the potential environmental impacts on air quality and ocean acidity, must be carefully considered before any action is taken.

In response to the intensification of urbanization, characterized by increasingly dense land use, the proliferation of high-rise residences has emerged as a predominant housing solution, particularly evident in developed cities like those in China. With a primary aim of enhancing the residential living environment within high-rise structures, this study advocates for a comprehensive whole life cycle perspective. By employing digital technology and conducting experiments centered on a representative case study, this paper focuses on optimizing the functional layout of public activity spaces within high-rise residential projects. Specifically, this article aims to address challenges such as the inadequate configuration and articulation of various public spaces, along with the underutilization of peripheral activity areas. Central to the optimization efforts is the utilization of the Kruskal algorithm, which enables the analysis of flow lines and functions, ultimately leading to the derivation of optimal solutions. Through a detailed analysis of our case study, this paper provides actionable insights into enhancing the feasibility and effectiveness of public spaces within high-rise residential projects. Recognizing the pivotal role of public space layout in shaping residents’ living experiences, the importance of addressing this issue early in the design phase was emphasized. By integrating scientifically driven digital technology solutions, smart, inclusive, and convenient communities that cater to the diverse needs of their inhabitants are aspired to be created.

Observations are reported of HClO3 and HClO4 in the atmosphere and their widespread occurrence over the pan-Arctic during spring, providing further insights into atmospheric chlorine cycling in the polar environment.

Tumor vaccines have been considered a promising therapeutic approach for treating cancer in recent years. With the development of sequencing technologies, tumor vaccines based on neoantigens or genomes specifically expressed in tumor cells, mainly in the form of peptides, nucleic acids, and dendritic cells, are beginning to receive widespread attention. Therefore, in this review, we have introduced different forms of neoantigen vaccines and discussed the development of these vaccines in treating cancer. Furthermore, neoantigen vaccines are influenced by factors such as antigen stability, weak immunogenicity, and biosafety in addition to sequencing technology. Hence, the biological nanomaterials, polymeric nanomaterials, inorganic nanomaterials, etc., used as vaccine carriers are principally summarized here, which may contribute to the design of neoantigen vaccines for improved stability and better efficacy.

Keeping global surface temperatures below international climate targets will require substantial measures to control atmospheric CO _2 and CH _4 concentrations. Recent studies have focused on interventions to decrease CH _4 through enhanced atmospheric oxidation. Here for the first time using a set of models, we evaluate the effect of adding iron aerosols to the atmosphere to enhance molecular chlorine production, and thus enhance the atmospheric oxidation of methane and reduce its concentration. Using different iron emission sensitivity scenarios, we examine the potential role and impact of enhanced iron emissions on direct interactions with solar radiation, and on the chemical and radiative response of methane. Our results show that the impact of iron emissions on CH _4 depends sensitively on the location of the iron emissions. In all emission regions there is a threshold in the amount of iron that must be added to remove methane. Below this threshold CH _4 increases. Even once that threshold is reached, the iron-aerosol driven chlorine-enhanced impacts on climate are complex. The radiative forcing of both methane and ozone are decreased in the most efficient regions but the direct effect due to the addition of absorbing iron aerosols tends to warm the planet. Adding any anthropogenic aerosol may also cool the planet due to aerosol cloud interactions, although these are very uncertain, and here we focus on the unique properties of adding iron aerosols. If the added emissions have a similar distribution as current shipping emissions, our study shows that the amount of iron aerosols that must be added before methane decreases is 2.5 times the current shipping emissions of iron aerosols, or 6 Tg Fe yr ^−1 in the most ideal case examined here. Our study suggests that the photoactive fraction of iron aerosols is a key variable controlling the impact of iron additions and poorly understood. More studies of the sensitivity of when, where and how iron aerosols are added should be conducted. Before seriously considering this method, additional impacts on the atmospheric chemistry, climate, environmental impacts and air pollution should be carefully assessed in future studies since they are likely to be important.

The reaction of CH _4 with chlorine (Cl) radicals in the atmosphere is associated with an extraordinarily strong isotopic fractionation, where ^12 CH _4 reacts about 70 ‰ faster with Cl than ^13 CH _4 . Therefore, although the Cl-based sink of CH _4 constitutes only a small contribution to its total removal rate, the uncertainty in this small sink has been identified as one of the two largest uncertainties of isotope-based CH _4 source apportionment at the global scale. The uncertainty arises from the fact that Cl levels in the atmosphere are so low that they cannot be detected directly. One very sensitive indirect method to identify and quantify the CH _4 + Cl reaction in the atmosphere is the detection of the extremely ^13 C-depleted reaction product carbon monoxide (CO) from this reaction. This article reviews the concept of this approach, its successful application in the atmosphere, its challenges and opportunities for identifying and quantifying Cl-based removal of CH _4 at the regional and global scale and its potential to detect and evaluate possible attempts to enhance CH _4 removal from the atmosphere.

Methane is a powerful greenhouse gas and previous studies focus on its sources with less attention on the loss. Here the authors show that reactive halogen species, not considered in climate projections, significantly reduces the methane loss, increasing its lifetime, burden, and radiative forcing.

Abstract Objective To explore the impacts of surgical mask in normal subjects on cardiopulmonary function and muscle performance under different motor load and gender differences. Design Randomized crossover trial. Setting The Fifth Affiliated Hospital of Guangzhou Medical University, June 16th to December 30th, 2020. Participants Thirty-one college students (age: male 21.27 ± 1.22 years; female 21.31 ± 0.79 years) were recruited and randomly allocated in two groups. Interventions Group 1 first received CPET in the mask-on condition followed by 48 h of washout, and then received CPET in the mask-off condition. Group 2 first received CPET in the mask-off condition followed by 48 h of washout, then received CPET in the mask-on condition. The sEMG data were simultaneously collected. Main outcome measures The primary outcome was maximum oxygen uptake (VO2 max) from CPET, which was performed on a cycle ergometer—this is the most important parameter associated with an individual’s physical conditioning. The secondary parameters included parameters reflecting exercise tolerance and heart function (oxygen uptake, anaerobic valve, maximum oxygen pulse, heart rate reserve), parameters reflecting ventilation function (respiration reserve, ventilation volume, tidal volume, breathing frequency), parameters reflecting gas exchange (end-tidal oxygen and carbon dioxide partial pressure, oxygen equivalent, carbon dioxide equivalent, and the relationship between dead space and tidal volume) and parameters reflecting skeletal muscle function [oxygen uptake, anaerobic valve, work efficiency, and EMG parameters including root mean square (RMS)]. Results Comparing the mask-on and mask-off condition, wearing surgical mask had some negative effects on VO2/kg (peak) and ventilation (peak) in both male and female health subjects [VO2/kg (peak): 28.65 ± 3.53 vs 33.22 ± 4.31 (P = 0.001) and 22.54 ± 3.87 vs 26.61 ± 4.03 (P

This study unravels an important daytime Cl2 source in the extra-polar atmosphere and shows that photolysis of particle nitrate at high acidity produced unprecedented levels of Cl2, boosting the oxidative power and air pollutants like O3.

As a key component of electric drive assembly of electric vehicles，the reducer is one of the main noise sources of electric vehicles.The noise level of the reducer is directly related to electric vehicle noise，vibration， harshness （for short NVH） performance and passenger comfort.Taking a certain type of reducer as the research object，the mechanism of vibration and noise generation of the reducer is analyzed. On this basis，four simulation indicators for evaluating the NVH of the reducer are introduced: transmission error of the reducer，contact spots，dynamic stiffness of the bearing seat and modal.Based on these four indicators，simulation research and test benchmarking are carried out respectively.The results show the simulation and test results are in good agreement.Based on the above research results，the transmission error and contact spots of the two-stage gear of the reducer need to be optimized. Through strengthening of spoke structures and modification of gear teeth，the results show that the simulation transmission error and contact spots of the secondary gear can be improved and the noise of the optimized scheme test can also be reduced.

Background & Aims: Non-invasive stratification of the liver decompensation risk remains unmet in people with compensated cirrhosis. This study aimed to develop a non-invasive tool (NIT) to predict hepatic decompensation. Methods: This retrospective study recruited 689 people with compensated cirrhosis (median age, 54 years; 441 men) from 5 centres from January 2016 to June 2020. Baseline abdominal computed tomography (CT), clinical features, and liver stiffness were collected, and then the first decompensation was registered during the follow-up. The spleen-based model was designed for predicting decompensation based on a deep learning segmentation network to generate the spleen volume and least absolute shrinkage and selection operator (LASSO)-Cox. The spleen-based model was trained on the training cohort of 282 individuals (Institutions I–III) and was validated in 2 external validation cohorts (97 and 310 individuals from Institutions IV and V, respectively) and compared with the conventional serum-based models and the Baveno VII criteria. Results: The decompensation rate at 3 years was 23%, with a 37.6-month median (IQR 21.1–52.1 months) follow-up. The proposed model showed good performance in predicting decompensation (C-index ≥0.84) and outperformed the serum-based models (C-index comparison test p

BackgroundMild cognitive impairment (MCI) is considered a transitional stage between cognitive normality and dementia among the elderly, and its associated risk of developing Alzheimer’s disease (AD) is 10–15 times higher than that of the general population. MCI is an important threshold for the prevention and control of AD, and intervention in the MCI stage may be the most effective strategy to delay the occurrence of AD.Materials and methodsIn this study, 68 subjects who met the inclusion criteria were divided into an MCI group (38 subjects) and normal elderly (NE) group (30 subjects). Both groups underwent clinical function assessments (cognitive function, walking function, and activities of daily living) and dual-task three-dimensional gait analysis (walking motor task and walking calculation task). Spatial-temporal parameters were obtained and reduced by principal component analysis, and the key biomechanical indexes were selected. The dual-task cost (DTC) was calculated for intra-group (task factor) and inter-group (group factor) comparisons.ResultsThe results of the principal component analysis showed that the cadence parameter had the highest weight in all three walking tasks. In addition, there were significant differences in the cadence both walking motor task (WMT) vs. walking task (WT) and walking calculation task (WCT) vs. WT in the MCI group. The cadence in the NE group only showed a significant difference between WMT and WT. The only differences between the MCI group and NE group was DTC cadence in WCT, and no differences were found for cadence in any of the three walking tasks.ConclusionThe results show that dual tasks based on cognitive-motor gait analysis of DTCcadence in MCI have potential value for application in early identification and provide theoretical support to improve the clinical diagnosis of MCI.

This study investigates the association between work-family conflict and organizational citizenship behavior and examines the mediated role of subjective happiness between and the moderated part of family support. A moderated mediation model is established based on the Conservation of Resources theory. We collected data from 386 employees of nine companies in China. This study shows that the work-family conflict of female professional employees is negatively correlated with organizational citizenship behavior, and that the relationship is mediated by subjective well-being. Furthermore, female professional employees’ family support moderates the effects of work-family conflict on subjective happiness and organizational citizenship behavior, with the relationship weaker when family support is higher. This study enriches the literature on work-family conflict by using family support as a mediating mechanism for work-family conflict. It enhanced our understanding of the influencing mechanisms of organizational citizenship behavior by constructing a more detailed model.

The activation energy of particle aggregation in suspensions is a very important kinetic parameter in a wide range of science and engineering applications. At present, however, there is no theory that can theoretically predict the activation energy. Because the activation energy is often less than 10 kT (where k is the Boltzmann constant and T is the temperature), it is difficult to experimentally measure. In this study, a theory for calculating the activation energy is established. Experimental measurements of the activation energy of montmorillonite aggregation were performed with different electrolyte and particle concentrations using the dynamic light scattering (DLS) technique. The validity of the theory was verified by the experiments. This study confirmed that both the method for activation energy measurements by DLS and the theory for its calculation can be applied to suspensions of polydisperse nonspherical particles. The average kinetic energy at the moment of particle collision in the aggregation process was found to be 0.2 kT, which is less than the instantaneous kinetic energy of a Brownian particle (0.5 kT) because of the viscous resistance of the water medium. This study also shows that adsorbed Na+ is strongly polarized in the electric field near the particle surface, and the polarization increases the effective charge of Na+ from +1 to +1.18.

While the dominant role of halogens in Arctic ozone loss during spring has been widely studied in the last decades, the impact of sea-ice halogens on surface ozone abundance over the northern hemisphere (NH) mid-latitudes remains unquantified. Here, we use a state-of-the-art global chemistry-climate model including polar halogens (Cl, Br, and I), which reproduces Arctic ozone seasonality, to show that Arctic sea-ice halogens reduce surface ozone in the NH mid-latitudes (47°N to 60°N) by ~11% during spring. This background ozone reduction follows the southward export of ozone-poor and halogen-rich air masses from the Arctic through polar front intrusions toward lower latitudes, reducing the springtime tropospheric ozone column within the NH mid-latitudes by ~4%. Our results also show that the present-day influence of Arctic halogens on surface ozone destruction is comparatively smaller than in preindustrial times driven by changes in the chemical interplay between anthropogenic pollution and natural halogens. We conclude that the impact of Arctic sea-ice halogens on NH mid-latitude ozone abundance should be incorporated into global models to improve the representation of ozone seasonality. [ABSTRACT FROM AUTHOR]

Mercury (Hg) is a contaminant of global concern, and an accurate understanding of its atmospheric fate is needed to assess its risks to humans and ecosystem health. Atmospheric oxidation of Hg is key to the deposition of this toxic metal to the Earth's surface. Short-lived halogens (SLHs) can provide halogen radicals to directly oxidize Hg and perturb the budget of other Hg oxidants (e.g., OH and O3). In addition to known ocean emissions of halogens, recent observational evidence has revealed abundant anthropogenic emissions of SLHs over continental areas. However, the impacts of anthropogenic SLHs emissions on the atmospheric fate of Hg and human exposure to Hg contamination remain unknown. Here, we show that the inclusion of anthropogenic SLHs substantially increased local Hg oxidation and, consequently, deposition in/near Hg continental source regions by up to 20%, thereby decreasing Hg export from source regions to clean environments. Our modeling results indicated that the inclusion of anthropogenic SLHs can lead to higher Hg exposure in/near Hg source regions than estimated in previous assessments, e.g., with increases of 8.7% and 7.5% in China and India, respectively, consequently leading to higher Hg-related human health risks. These results highlight the urgent need for policymakers to reduce local Hg and SLHs emissions. We conclude that the substantial impacts of anthropogenic SLHs emissions should be included in model assessments of the Hg budget and associated health risks at local and global scales. [ABSTRACT FROM AUTHOR]