The resulting larvae are killed during growth and development The phenomenon of volatile-mediated attraction and specialized metabolite toxicity suggests that some streptomycetes pose an evolutionary risk to insects in natureAlthough the efficacy of cancer radiotherapy RT can be enhanced by targeted immunotherapy, the immunosuppressive factors induced by radiation on tumor cells remain to be identified Here, we report that CD47-mediated anti-phagocytosis is concurrently upregulated with HER2 in radioresistant breast cancer BC cells and RT-treated mouse syngeneic BC Co-expression of both receptors is more frequently detected in recurrent BC patients with poor prognosis CD47 is upregulated preferentially in HER2-expressing cells, and blocking CD47 or HER2 reduces both receptors with diminished clonogenicity and augmented phagocytosis CRISPR-mediated CD47 and HER2 dual knockouts not only inhibit clonogenicity but also enhance macrophage-mediated attack Dual antibody of both receptors synergizes with RT in control of syngeneic mouse breast tumor These results provide the evidence that aggressive behavior of radioresistant BC is caused by CD47-mediated anti-phagocytosis conjugated with HER2-prompted proliferation Dual blockade of CD47 and HER2 is suggested to eliminate resistant cancer cells in BC radiotherapyEarlier studies indicate that either the canonical or non-canonical pathways of inflammasome activation have a limited role on malaria pathogenesis Here, we report that caspase-8 is a central mediator of systemic inflammation, septic shock in the Plasmodium chabaudi-infected mice and the P berghei-induced experimental cerebral malaria ECM Importantly, our results indicate that the combined deficiencies of caspases-8/1/11 or caspase-8/gasdermin-D GSDM-D renders mice impaired to produce both TNFα and IL-1β and highly resistant to lethality in these models, disclosing a complementary, but independent role of caspase-8 and caspases-1/11/GSDM-D in the pathogenesis of malaria Further, we find that monocytes from malaria patients express active caspases-1, -4 and -8 suggesting that these inflammatory caspases may also play a role in the pathogenesis of human diseaseDeveloping a high-performance donor polymer is critical for achieving efficient non-fullerene organic solar cells OSCs Currently, most high-efficiency OSCs are based on a donor polymer named PM6, unfortunately, whose performance is highly sensitive to its molecular weight and thus has significant batch-to-batch variations Here we report a donor polymer named PM1 based on a random ternary polymerization strategy that enables highly efficient non-fullerene OSCs with efficiencies reaching 176 Importantly, the PM1 polymer exhibits excellent batch-to-batch reproducibility By including 20 of a weak electron-withdrawing thiophene-thiazolothiazole TTz into the PM6 polymer backbone, the resulting polymer PM1 can maintain the positive effects such as downshifted energy level and reduced miscibility while minimize the negative ones including reduced temperature-dependent aggregation property With higher performance and greater synthesis reproducibility, the PM1 polymer has the promise to become the work-horse material for the non-fullerene OSC communityDrug tolerance is the basis for acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors EGFR-TKIs including osimertinib, through mechanisms that still remain unclear Here, we show that while AXL-low expressing EGFR mutated lung cancer EGFRmut-LC cells are more sensitive to osimertinib than AXL-high expressing EGFRmut-LC cells, a small population emerge osimertinib tolerance The tolerance is mediated by the increased expression and phosphorylation of insulin-like growth factor-1 receptor IGF-1R, caused by the induction of its transcription factor FOXA1 IGF-1R maintains association with EGFR and adaptor proteins, including Gab1 and IRS1, in the presence of osimertinib and restores the survival signal In AXL-low-expressing EGFRmut-LC cell-derived xenograft and patient-derived xenograft models, transient IGF-1R inhibition combined with continuous osimertinib treatment could eradicate tumors and prevent regrowth even after the cessation of osimertinib These results indicate that optimal inhibition of tolerant signals combined with osimertinib may dramatically improve the outcome of EGFRmut-LCCASK-related disorders are genetically defined neurodevelopmental syndromes There is limited information about the effects of CASK mutations in human neurons Therefore, we sought to delineate CASK-mutation consequences and neuronal effects using induced pluripotent stem cell-derived neurons from two mutation carriers One male case with autism spectrum disorder carried a novel splice-site mutation and a female case with intellectual disability carried an intragenic tandem duplication We show reduction of CASK protein in maturing neurons from the mutation carriers, which leads to significant downregulation of genes involved in presynaptic development and of CASK protein interactors Furthermore, CASK-deficient neurons showed decreased inhibitory presynapse size as indicated by VGAT staining, which may alter the excitatory-inhibitory E/I balance in developing neural circuitries Using in vivo magnetic resonance spectroscopy quantification of GABA in the male mutation carrier, we further highlight the possibility to validate in vitro cellular data in the brain Our data show that future pharmacological and clinical studies on targeting presynapses and E/I imbalance could lead to specific treatments for CASK-related disordersAmino acid propensities at a site change in the course of protein evolution This may happen for two reasons Changes may be triggered by substitutions at epistatically interacting sites elsewhere in the genome Alternatively, they may arise due to environmental changes that are external to the genome Here, we design a framework for distinguishing between these alternatives Using analytical modelling and simulations, we show that they cause opposite dynamics of the fitness of the allele currently occupying the site it tends to increase with the time since its origin due to epistasis "entrenchment", but to decrease due to random environmental fluctuations "senescence" By analysing the genomes of vertebrates and insects, we show that the amino acids originating at negatively selected sites experience strong entrenchment By contrast, the amino acids originating at positively selected sites experience senescence We propose that senescence of the current allele is a cause of adaptive evolutionThe current opioid epidemic necessitates a better understanding of human addiction neurobiology to develop efficacious treatment approaches Here, we perform genome-wide assessment of chromatin accessibility of the human striatum in heroin users and matched controls Our study reveals distinct neuronal and non-neuronal epigenetic signatures, and identifies a locus in the proximity of the gene encoding tyrosine kinase FYN as the most affected region in neurons FYN expression, kinase activity and the phosphorylation of its target Tau are increased by heroin use in the post-mortem human striatum, as well as in rats trained to self-administer heroin and primary striatal neurons treated with chronic morphine in vitro Pharmacological or genetic manipulation of FYN activity significantly attenuates heroin self-administration and responding for drug-paired cues in rodents Our findings suggest that striatal FYN is an important driver of heroin-related neurodegenerative-like pathology and drug-taking behavior, making FYN a promising therapeutic target for heroin use disorderExploring photocatalysts to promote CO2 photoreduction into solar fuels is of great significance We develop TiO2/perovskite CsPbBr3 S-scheme heterojunctions synthesized by a facile electrostatic-driven self-assembling approach  https//wwwselleckchemcom/products/cpi-613html  Density functional theory calculation combined with experimental studies proves the electron transfer from CsPbBr3 quantum dots QDs to TiO2, resulting in the construction of internal electric field IEF directing from CsPbBr3 to TiO2 upon hybridization The IEF drives the photoexcited electrons in TiO2 to CsPbBr3 upon light irradiation as revealed by in-situ X-ray photoelectron spectroscopy analysis, suggesting the formation of an S-scheme heterojunction in the TiO2/CsPbBr3 nanohybrids which greatly promotes the separation of electron-hole pairs to foster efficient CO2 photoreduction The hybrid nanofibers unveil a higher CO2-reduction rate 902 μmol g-1 h-1 comparing with pristine TiO2 nanofibers 468 μmol g-1 h-1 Isotope 13CO2 tracer results confirm that the reduction products originate from CO2 sourceNecrotizing enterocolitis NEC is a devastating intestinal disease primarily affecting preterm neonates and causing high morbidity, high mortality, and huge costs for the family and society The treatment and the outcome of the disease have not changed in recent decades Emerging evidence has shown that stimulating the Wnt/β-catenin pathway and enhancing intestinal regeneration are beneficial in experimental NEC, and that they could potentially be used as a novel treatment Amniotic fluid stem cells AFSC and AFSC-derived extracellular vesicles EV can be used to improve intestinal injury in experimental NEC However, the mechanisms by which they affect the Wnt/β-catenin pathway and intestinal regeneration are unknown In our current study, we demonstrated that AFSC and EV attenuate NEC intestinal injury by activating the Wnt signaling pathway AFSC and EV stimulate intestinal recovery from NEC by increasing cellular proliferation, reducing inflammation and ultimately regenerating a normal intestinal epithelium EV administration has a rescuing effect on intestinal injury when given during NEC induction; however, it failed to prevent injury when given prior to NEC induction AFSC-derived EV administration is thus a potential emergent novel treatment strategy for NECAlthough ferroptosis has been recognized as a novel antitumoral treatment, high expression of nuclear factor erythroid 2-related factor 2 NRF2 has been reported to be an antioxidant transcript factor that protects malignant cells from ferroptosis Previous findings indicated that metallothionein 1D pseudogene MT1DP, a long noncoding RNA lncRNA, functioned to aggravate oxidative stress by repressing antioxidation Here we aimed at assessing whether MT1DP could regulate erastin-induced ferroptosis on non-small cell lung cancer NSCLC and elucidating the mechanism We found that ectopic expression of MT1DP sensitized A549 and H1299 cells to erastin-induced ferroptosis through downregulation of NRF2; in addition, ectopic MT1DP upregulated malondialdehyde MDA and reactive oxygen species ROS levels, increased intracellular ferrous iron concentration, and reduced glutathione GSH levels in cancer cells exposed to erastin, whereas downregulation of MT1DP showed the opposite effect RNA pulldown assay and dual-luciferase reporter assay confirmed that MT1DP modulated the expression of NRF2 via stabilizing miR-365a-3p As low solubility of erastin limits its efficient application, we further prepared folate FA-modified liposome FA-LP nanoparticles for targeted co-delivery of erastin and MT1DP to enhance the bioavailability and the efficiency of the drug/gene combination Erastin/MT1DPFA-LPs E/MFA-LPs sensitized erastin-induced ferroptosis with decreased cellular GSH levels and elevated lipid ROS In vivo analysis showed that E/MFA-LPs had a favorable therapeutic effect on lung cancer xenografts In short, our findings identify a novel strategy to elevate erastin-induced ferroptosis in NSCLCs acting through the MT1DP/miR-365a-3p/NRF2 axis