Explore the vast range of titles available.

Some developed economies have run emission trading scheme (ETS) to mitigate carbon emissions. However, we know little about the effectiveness and heterogeneity of ETS in a context of developing economy. This paper evaluates the effectiveness and heterogeneity of China’s pilot ETS, the first ETS run in a developing economy. Difference-in-difference (DID) and difference-in-difference-in-difference (DDD) methods are employed to analyze provincial industrial-level data. The heterogeneity of ETS effects is also explored from regional and industrial perspectives. The empirical results show that the pilot ETS can effectively reduce pilot industries’ carbon emissions. The reduction effect of the pilot ETS has a substantial heterogeneity for different pilot provinces and industries. Carbon emissions are reduced by the pilot ETS through technological innovation and the adjustment of industrial structure. The empirical results suggest that policymakers may consider establishing a national ETS and differentiating carbon quota allowance in covered regions and industries in the current pilot ETS.

The directional transformation of carbon dioxide (CO 2 ) with renewable hydrogen into specific carbon-heavy products (C 6+ ) of high value presents a sustainable route for net-zero chemical manufacture. However, it is still challenging to simultaneously achieve high activity and selectivity due to the unbalanced CO 2 hydrogenation and C–C coupling rates on complementary active sites in a bifunctional catalyst, thus causing unexpected secondary reaction. Here we report LaFeO 3 perovskite-mediated directional tandem conversion of CO 2 towards heavy aromatics with high CO 2 conversion (> 60%), exceptional aromatics selectivity among hydrocarbons (> 85%), and no obvious deactivation for 1000 hours. This is enabled by disentangling the CO 2 hydrogenation domain from the C-C coupling domain in the tandem system for Iron-based catalyst. Unlike other active Fe oxides showing wide hydrocarbon product distribution due to carbide formation, LaFeO 3 by design is endowed with superior resistance to carburization, therefore inhibiting uncontrolled C–C coupling on oxide and isolating aromatics formation in the zeolite. In-situ spectroscopic evidence and theoretical calculations reveal an oxygenate-rich surface chemistry of LaFeO 3 , that easily escape from the oxide surface for further precise C–C coupling inside zeolites, thus steering CO 2 -HCOOH/H 2 CO-Aromatics reaction pathway to enable a high yield of aromatics. The transformation of CO2 with renewable hydrogen into high-value products presents a sustainable route for net-zero chemical manufacture. Here the authors introduce a LaFeO3 perovskite-mediated tandem conversion of CO2, achieving remarkable performance by separating the CO2 hydrogenation and C-C coupling domains in the catalyst system.

CD8 + T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8 + T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue to induce CD8 + T cell exhaustion within tumor microenvironments. We find that a continuously high level of IL-2 leads to the persistent activation of STAT5 in CD8 + T cells, which in turn induces strong expression of tryptophan hydroxylase 1, thus catalyzing the conversion to tryptophan to 5-hydroxytryptophan (5-HTP). 5-HTP subsequently activates AhR nuclear translocation, causing a coordinated upregulation of inhibitory receptors and downregulation of cytokine and effector-molecule production, thereby rendering T cells dysfunctional in the tumor microenvironment. This molecular pathway is not only present in mouse tumor models but is also observed in people with cancer, identifying IL-2 as a novel inducer of T cell exhaustion. IL-2 is a classic T cell growth factor. Huang and colleagues demonstrate, however, that chronic IL-2 stimulation leads to a new exhaustion pathway that impairs antitumor immune responses.

The emergence of genetic data coupled to longitudinal electronic medical records (EMRs) offers the possibility of phenome-wide association studies (PheWAS). In PheWAS, the whole phenome can be divided into numerous phenotypic categories according to the genetic architecture across phenotypes. Currently, statistical analyses for PheWAS are mainly univariate analyses, which test the association between one genetic variant and one phenotype at a time. In this article, we derived a novel and powerful multivariate method for PheWAS. The proposed method involves three steps. In the first step, we apply the bottom-up hierarchical clustering method to partition a large number of phenotypes into disjoint clusters within each phenotypic category. In the second step, the clustering linear combination method is used to combine test statistics within each category based on the phenotypic clusters and obtain p-values from each phenotypic category. In the third step, we propose a new false discovery rate (FDR) control approach. We perform extensive simulation studies to compare the performance of our method with that of other existing methods. The results show that our proposed method controls FDR very well and outperforms other methods we compared with. We also apply the proposed approach to a set of EMR-based phenotypes across more than 300,000 samples from the UK Biobank. We find that the proposed approach not only can well-control FDR at a nominal level but also successfully identify 1,244 significant SNPs that are reported to be associated with some phenotypes in the GWAS catalog. Our open-access tools and instructions on how to implement HCLC-FC are available at https://github.com/XiaoyuLiang/HCLCFC .

Resetting tumor-associated macrophages (TAMs) is a promising strategy to ameliorate the immunosuppressive tumor microenvironment and improve innate and adaptive antitumor immunity. Here we show that chloroquine (CQ), a proven anti-malarial drug, can function as an antitumor immune modulator that switches TAMs from M2 to tumor-killing M1 phenotype. Mechanistically, CQ increases macrophage lysosomal pH, causing Ca 2+ release via the lysosomal Ca 2+ channel mucolipin-1 (Mcoln1), which induces the activation of p38 and NF-κB, thus polarizing TAMs to M1 phenotype. In parallel, the released Ca 2+ activates transcription factor EB (TFEB), which reprograms the metabolism of TAMs from oxidative phosphorylation to glycolysis. As a result, CQ-reset macrophages ameliorate tumor immune microenvironment by decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and Treg cells, thus enhancing antitumor T-cell immunity. These data illuminate a previously unrecognized antitumor mechanism of CQ, suggesting a potential new macrophage-based tumor immunotherapeutic modality. Tumour-associated macrophages (TAMs) display an M2 phenotype that promote tumour immune escape. Here the authors show that Chloroquine (CQ), a lysosome inhibitor used against malaria, inhibits tumour growth by switching TAMs into an M1 tumor-killing phenotype by repolarizing macrophages metabolism.

Glycogen has long been considered to have a function in energy metabolism. However, our recent study indicated that glycogen metabolism, directed by cytosolic phosphoenolpyruvate carboxykinase Pck1, controls the formation and maintenance of CD8+ memory T (Tmem) cells by regulating redox homeostasis1. This unusual metabolic program raises the question of how Pck1 is upregulated in CD8+ Tmem cells. Here, we show that mitochondrial acetyl coenzyme A is diverted to the ketogenesis pathway, which indirectly regulates Pck1 expression. Mechanistically, ketogenesis-derived β-hydroxybutyrate is present in CD8+ Tmem cells; β-hydroxybutyrate epigenetically modifies Lys 9 of histone H3 (H3K9) of Foxo1 and Ppargc1a (which encodes PGC-1α) with β-hydroxybutyrylation, upregulating the expression of these genes. As a result, FoxO1 and PGC-1α cooperatively upregulate Pck1 expression, therefore directing the carbon flow along the gluconeogenic pathway to glycogen and the pentose phosphate pathway. These results reveal that ketogenesis acts as an unusual metabolic pathway in CD8+ Tmem cells, linking epigenetic modification required for memory development.Zhang et al. show that ketogenesis-derived β-hydroxybutyrate (BHB) epigenetically modifies H3K9 of Foxo1 and Ppargc1a to regulate Pck1, which in turn controls metabolic flux and CD8+ memory T-cell development.

Background Adolescents are increasingly recognized as important stakeholders in responding to the challenges of climate change, with their psychological responses shaping both mental health outcomes and behavioral choices. However, the intricate relationship between climate change awareness and climate change anxiety among adolescents, as significant manifestations of psychological reactions to climate change, has not yet been thoroughly investigated. Grounded in the Stress and Coping Theory, this study aimed to empirically investigate the bidirectional relationship between climate change awareness and climate change anxiety among Chinese adolescents. Methods Data were collected through a three-wave longitudinal survey (2022–2024) from 426 Chinese adolescents. We employed repeated measures ANOVA to examine developmental patterns and gender differences in climate change awareness and climate change anxiety, and constructed cross-lagged panel models, along with the calculation of feedback effects, to investigate their reciprocal relationships across time points. Results Results revealed significant increases in both climate change awareness and climate change anxiety over time, with females consistently exhibiting higher levels. Cross-lagged analyses demonstrated that climate change awareness significantly predicted an increase in climate change anxiety, and climate change anxiety, in turn, significantly enhanced climate change awareness. Furthermore, the feedback effect between climate change awareness and climate change anxiety was significant at both T1-T2 and T2-T3 intervals. Conclusion This study demonstrates a bidirectional relationship between climate change awareness and anxiety among adolescents, providing a theoretical framework and empirical evidence for understanding adolescents’ complex psychological responses to climate change. It also presents valuable suggestions for implementing targeted mental health interventions, and climate change education.

Background Analyses of a bipartite Genotype and Phenotype Network (GPN), linking the genetic variants and phenotypes based on statistical associations, provide an integrative approach to elucidate the complexities of genetic relationships across diseases and identify pleiotropic loci. In this study, we assess contributions to constructing a well-defined GPN with a clear representation of genetic associations by comparing the network properties with a random network, including connectivity, centrality, and community structure. Then, we extend our discussion to include two applications of bipartite GPN in disease heritability enrichment analysis and phenome-wide association studies (PheWAS). Results We construct network topology annotations of genetic variants that quantify the possibility of pleiotropy and apply stratified linkage disequilibrium (LD) score regression to 12 highly genetically correlated phenotypes to identify enriched annotations. The constructed network topology annotations are informative for disease heritability after conditioning on a broad set of functional annotations from the baseline-LD model. In application of PheWAS, the community detection method can be used to obtain a priori grouping of phenotypes detected from GPN based on the shared genetic architecture, then jointly test the association between multiple phenotypes in each network module and one genetic variant to discover the cross-phenotype associations and pleiotropy. Significance thresholds for PheWAS are adjusted for multiple testing by applying the false discovery rate (FDR) control approach. Extensive simulation studies and analyses of 633 electronic health record (EHR)-derived phenotypes in the UK Biobank GWAS summary dataset reveal that most multiple phenotype association tests based on GPN can well-control FDR and identify more significant genetic variants compared with the tests based on UK Biobank categories. Conclusions The construction and integration of the bipartite GPNs enhance our understanding of disease heritability, genetic architecture between phenotypes, and pleiotropy.

The induction of type-I interferons (IFN-Is) is important for the efficacy of chemotherapy. By investigating the role of amino acids in regulation of IFN-I production under chemo-drug treatment in bladder cancer (BC) cells, we find an inherent AhR-dependent negative feedback to restrain STING signaling and IFN-I production. Mechanistically, in a ligand dependent manner, AhR bridges STING and CUL4B/RBX1 E3 ligase complex, facilitating STING degradation through ubiquitin-proteasome pathway. Inhibition of AhR increases STING levels and reduces tumor growth under cisplatin or STING agonist treatment. Endogenous AhR ligands are mainly consisted of tryptophan (Trp) metabolites; dietary Trp restriction, blocking the key Trp metabolism rate-limiting enzyme IDO1 or inhibition of cellular Trp importation also show similar effect as AhR inhibition. Clinically, BC patients with higher intratumoral expression of AhR or stronger intratumoral Trp metabolism (higher IDO1 or Kyn levels) that lead to higher AhR activation show worse response rate to neoadjuvant chemotherapy (NAC). An effective response to chemotherapy is often associated with the promotion of type-I interferons and anti-tumor immune responses. Here the authors show that tryptophan metabolites induced by chemo-drugs interfere with STING activation and IFN-I production in bladder cancer, reducing the efficacy of chemotherapy.

Stem-end rot (SER) caused by Lasiodiplodia theobromae is an important disease of mango in China. Demethylation inhibitor (DMI) fungicides are widely used for disease control in mango orchards. The baseline sensitivity to difenoconazole of 138 L. theobromae isolates collected from mango in the field in 2019 was established by the mycelial growth rate method. The cross-resistance to six site-specific fungicides with different modes of action were investigated using 20 isolates randomly selected. The possible mechanism for L. theobromae resistance to difenoconazole was preliminarily determined through gene sequence alignment and quantitative real-time PCR analysis. The results showed that the EC 50 values of 138 L. theobromae isolates to difenoconazole ranged from 0.01 to 13.72 µg/mL. The frequency of difenoconazole sensitivity formed a normal distribution curve when the outliers were excluded. Difenoconazole showed positive cross-resistance only with the DMI tebuconazole but not with non-DMI fungicides carbendazim, pyraclostrobin, fludioxonil, bromothalonil, or iprodione. Some multifungicide-resistant isolates of L. theobromae were found. Two amino acid substitutions (E209k and G207A) were found in the CYP51 protein, but they were unlikely to be related to the resistance phenotype. There was no alteration in the promoter region of the CYP51 gene. However, difenoconazole significantly increased the expression of the CYP51 gene in the resistant isolates compared to the susceptible isolates. These results are vital to develop effective mango disease management strategies to avoid the development of further resistance.