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Previous studies have demonstrated a significant correlation between global average temperature change trends and greenhouse gases, and employed various prediction models. However, the potential of the combination of the LSTM and ARIMA models for temperature forecasting has not been fully explored, especially in terms of enhancing prediction accuracy. Based on the hypothesis that COVID-19 has affected the global average temperature, this study utilizes global average temperature data from 1880 to 2022. We combine the LSTM model, which excels at capturing long-term dependencies, with the ARIMA model, known for its effectiveness in handling linear time series data, to predict the global mean temperature. This combination compensated for the limitations of individual models, providing a more accurate and comprehensive temperature forecast. Our findings reveal that the early trend of global temperature rise is significant, yet the implementation delay leads to severe issues. Moreover, COVID-19 has indirectly reduced greenhouse gas emissions, slowing global warming. Additionally, we find that the correlation between longitude and mean temperature is weak, while the correlation between latitude and temperature is strongly negative. This study offers valuable insights and provides a reliable prediction method for ecological environment governance and the formulation of economic construction policies.

This study aims to explore the impact of the of food safety laws popularization on panic buying behavior towards ecological food, as well as the underlying mechanisms and boundary conditions. This study reveals that the food safety laws popularization unexpectedly intensifies, rather than alleviates, panic buying behavior towards ecological food. The core mechanism is that the information credibility and processing fluency associated with these laws enhance consumer trust in food safety and accelerate information internalization, indirectly promoting panic buying. Furthermore, purchase risk aversion moderates this effect: consumers with high aversion to risk perform stronger panic buying after food safety laws popularization, while those with low aversion respond more rationally. This study uncovers potential negative consequences of food safety laws popularization, analyzes its underlying mechanisms and boundary conditions, and offers crucial insights for policymakers who seek to guide consumer behavior and foster market health.

This study aims to provide an in-depth analysis of the influence and mechanisms of recycling and transformation information on product packaging towards tourists' purchasing intentions. Through four experiments, we found that product packaging featuring recycling and transformation information significantly enhanced tourists' purchase intentions, and this effect was partially mediated by tourists' Information seeking behavior. Notably, in the context of organic food packaging, tourists with a high level of environmental concern exhibited a more positive response to recycling and transformation information. Additionally, the study revealed that a positive environmental attitude strengthened the positive impact of recycling and transformation information on purchasing intentions. These findings not only enrich theoretical knowledge in the field of green consumption but also offer valuable practical guidance for businesses and governments in promoting environmentally friendly consumption practices.

Based on the previous studies on the impact of traditional culture on tourists’ purchasing intentions, this study aims to further explore the mechanism and boundary conditions regarding the traditional cultural load in tourist souvenir packaging. Through seven simulated experiments (N = 3203), the impact of different degrees of traditional cultural load on tourists’ purchasing intentions has been examined, with value perception, cultural identity, and purchase purpose, advancing the research in the field of traditional culture and tourism marketing. The findings provide insights for managers in the industry of tourism and souvenir marketing for their package design.

With the extensive application of artificial intelligence technology in the tourism industry, robot-assisted tourism has become a vital strategy for enhancing tourist experiences and promoting sustainable tourism practices. This study aims to explore the impact of language feedback from tourism robots on tourists’ ecotourism behavior and analyze potential mediating and moderating mechanisms. Through three experimental studies, we found that robot guides with language feedback capabilities significantly improve tourists’ ecotourism behavior. Specifically, environmental responsibility acts as a moderator between the robot’s language feedback and tourists’ ecotourism behavior, indicating that the robot’s language feedback is more effective when tourists have a higher sense of environmental responsibility. Furthermore, the robot’s language feedback enhances tourists’ environmental awareness and responsibility by increasing cognitive trust and feedback propensity. The findings have practical implications for tourism destinations and operators in designing and implementing intelligent tourism services to promote tourists’ ecological engagement.

Background BCR-ABL1 T315I mutations confer resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). Olverembatinib is a new potent BCR-ABL1 TKI with preclinical activity against T315I-mutated CML. In phase 1/2 studies, we explored the safety and efficacy of olverembatinib in Chinese adults with TKI-resistant CML in the chronic phase (CML-CP) and accelerated phase (CML-AP). Methods In the phase 1 study, olverembatinib was orally administered once every other day in 28-day cycles at 11 dose cohorts ranging from 1 to 60 mg, and we evaluated the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, efficacy, and pharmacokinetics of olverembatinib. In the phase 2 studies, olverembatinib was administered at the RP2D of 40 mg orally on alternate days for 28-day cycles. The primary outcome measure is major cytogenetic response (MCyR) and major hematologic response by the end of Cycle 12 in CML-CP and CML-AP, respectively. Fine and Gray's hazard models were used to identify covariates associated with responses. Results A total of 165 patients (> 80.0% of whom had received ≥ 2 TKIs) were enrolled in this study. Among 127 patients with CML-CP, the 3-year cumulative incidences of achieving MCyR, complete cytogenetic response (CCyR), major molecular response (MMR), MR 4.0 , and MR 4.5 were 79.0, 69.0, 56.0, 44.0 and 39.0%, respectively. The highest response rates were observed in patients with a single T315I mutation. Among 38 patients with CML-AP, the 3-year cumulative incidences of achieving MCyR, CCyR, MMR, MR 4.0 , and MR 4.5 were 47.4%, 47.4%, 44.7%, 39.3%, and 32.1%, respectively. In multivariate analyses, baseline BCR-ABL1 mutation status was significantly associated with cytogenetic and molecular responses. Common treatment-related adverse events included skin hyperpigmentation, hypertriglyceridemia, proteinuria, and severe thrombocytopenia. Conclusions Olverembatinib was well tolerated, with significant antileukemic activity in adults with TKI-resistant CML-CP and CML-AP, especially those with the T315I mutation. Trial registration : The phase 1 trial is registered at CTR20220566, and the two single-arm, open-label phase 2 studies are registered at ClinicalTrials.gov: NCT03883087 (CML-CP) and NCT03883100 (CML-AP).

Previous researches have shown that animal metaphors play an important role in promoting specific behavioral dispositions of individuals. However, we are not well aware of the role of animal metaphors in tourists’ waste classification intentions. Therefore, this study aimed to investigate the impact of animal metaphors advertising for waste classification in scenic spots (versus non-animal metaphors advertising) on tourists’ waste classification intentions. Four experiments (N = 1051) were conducted in this study to examine the impacts of animal metaphors advertising in scenic spots, on tourists’ waste classification intentions, which enriches the literature on the animal metaphors and tourists’ pro-environmental behaviors. The results show that the animal metaphors advertising about waste classification in scenic spots can effectively increase tourists’ waste classification intentions. We explored the mediating role of tourists’ perceptions of cute animal images in animal metaphors advertising, and the moderating role of visual imagery for animal metaphors advertising, on the relationship between animal metaphors advertising and tourists’ waste classification intentions. The results show that there is a significant interaction effect between visual imagery and animal metaphors advertising. In conclusion, this study reveals the different impacts of animal metaphors, cute images and visual imagery on individual tourists, which provides new insights for scenic spot managers to choose waste classification strategies and the looks of bins.

BackgroundProgrammed death-1 (PD-1) immune checkpoint blockade has achieved clinical successes in cancer therapy. However, the response rate of anti-PD-1 agents remains low. Additionally, a subpopulation of patients developed hyperprogressive disease upon PD-1 blockade therapy. Combination therapy with targeted agents may improve immunotherapy. Recent studies show that p53 activation in the myeloid linage suppresses alternative (M2) macrophage polarization, and attenuates tumor development and invasion, leading to the hypothesis that p53 activation may augment antitumor immunity elicited by anti-PD-1 therapy.MethodUsing APG-115 that is a MDM2 antagonist in clinical development as a pharmacological p53 activator, we investigated the role of p53 in immune modulation and combination therapy with PD-1 blockade.ResultsIn vitro treatment of bone marrow-derived macrophages with APG-115 resulted in activation of p53 and p21, and a decrease in immunosuppressive M2 macrophage population through downregulation of c-Myc and c-Maf. Increased proinflammatory M1 macrophage polarization was observed in the spleen from mice treated with APG-115. Additionally, APG-115 has co-stimulatory activity in T cells and increases PD-L1 expression in tumor cells. In vivo, APG-115 plus anti-PD-1 combination therapy resulted in enhanced antitumor activity in Trp53 wt , Trp53 mut , and Trp53-deficient (Trp53 −/− ) syngeneic tumor models. Importantly, such enhanced activity was abolished in a syngeneic tumor model established in Trp53 knockout mice. Despite differential changes in tumor-infiltrating leukocytes (TILs), including the increases in infiltrated cytotoxic CD8+ T cells in Trp53 wt tumors and M1 macrophages in Trp53 mut tumors, a decrease in the proportion of M2 macrophages consistently occurred in both Trp53 wt and Trp53 mut tumors upon combination treatment.ConclusionOur results demonstrate that p53 activation mediated by APG-115 promotes antitumor immunity in the tumor microenvironment (TME) regardless of the Trp53 status of tumors per se. Instead, such an effect depends on p53 activation in Trp53 wild-type immune cells in the TME. Based on the data, a phase 1b clinical trial has been launched for the evaluation of APG-115 in combination with pembrolizumab in solid tumor patients including those with TP53 mut tumors.

Background Tyrosine kinase inhibitors (TKIs) are mainstays of cancer treatment. However, their clinical benefits are often constrained by acquired resistance. To overcome such outcomes, we have rationally engineered APG-2449 as a novel multikinase inhibitor that is highly potent against oncogenic alterations of anaplastic lymphoma kinase ( ALK ), ROS proto-oncogene 1 receptor tyrosine kinase ( ROS1 ), and focal adhesion kinase ( FAK ). Here we present the preclinical evaluation of APG-2449, which exhibits antiproliferative activity in cells carrying ALK fusion or secondary mutations. Methods KINOMEscan® and LANCE TR-FRET were used to characterize targets and selectivity of APG-2449. Water-soluble tetrazolium salt (WST-8) viability assay and xenograft tumorigenicity were employed to evaluate therapeutic efficacy of monotherapy or drug combination in preclinical models of solid tumors. Western blot, pharmacokinetic, and flow cytometry analyses, as well as RNA sequencing were used to explore pharmacokinetic–pharmacodynamic correlations and the mechanism of actions driving drug combination synergy. Results In mice bearing wild-type or ALK/ROS1 -mutant non-small-cell lung cancer (NSCLC), APG-2449 demonstrates potent antitumor activity, with correlations between pharmacokinetics and pharmacodynamics in vivo. Through FAK inhibition, APG-2449 sensitizes ovarian xenograft tumors to paclitaxel by reducing CD44 + and aldehyde dehydrogenase 1-positive (ALDH1 + ) cancer stem cell populations, including ovarian tumors insensitive to carboplatin. In epidermal growth factor receptor ( EGFR) -mutated NSCLC xenograft models, APG-2449 enhances EGFR TKI-induced tumor growth inhibition, while the ternary combination of APG-2449 with EGFR (osimertinib) and mitogen-activated extracellular signal-regulated kinase (MEK; trametinib) inhibitors overcomes osimertinib resistance. Mechanistically, phosphorylation of ALK, ROS1, and FAK, as well as their downstream components, is effectively inhibited by APG-2449. Conclusions Taken together, our studies demonstrate that APG-2449 exerts potent and durable antitumor activity in human NSCLC and ovarian tumor models when administered alone or in combination with other therapies. A phase 1 clinical trial has been initiated to evaluate the safety and preliminary efficacy of APG-2449 in patients with advanced solid tumors, including ALK + NSCLC refractory to earlier-generation ALK inhibitors. Trial registration Clinicaltrial.gov registration: NCT03917043 (date of first registration, 16/04/2019) and Chinese clinical trial registration: CTR20190468 (date of first registration, 09/04/2019).

We have designed MI-219 as a potent, highly selective and orally active small-molecule inhibitor of the MDM2-p53 interaction. MI-219 binds to human MDM2 with a Ki value of 5 nM and is 10,000-fold selective for MDM2 over MDMX. It disrupts the MDM2-p53 interaction and activates the p53 pathway in cells with wild-type p53, which leads to induction of cell cycle arrest in all cells and selective apoptosis in tumor cells. MI-219 stimulates rapid but transient p53 activation in established tumor xenograft tissues, resulting in inhibition of cell proliferation, induction of apoptosis, and complete tumor growth inhibition. MI-219 activates p53 in normal tissues with minimal p53 accumulation and is not toxic to animals. MI-219 warrants clinical investigation as a new agent for cancer treatment.