Biomimetic biomineralization nanoplatform-mediated differentiation therapy and phototherapy for cancer stem cell inhibition and antitumor immunity activation

Growing evidence suggests that the presence of cancer stem cells(CSCs)is a major challenge in current tumor treatments,especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis.Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy.In this work,we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid(ATRA)via biomineralization.This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters,which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration.With the help of CSC differentiation induced by ATRA,IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner.Furthermore,ATRA can boost immunogenic cell death induced by phototherapy,thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells.Taken together,this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation,improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.

Future Changes in Extreme High Temperature over China at 1.5℃-5℃ Global Warming Based on CMIP6 Simulations

Extreme high temperature(EHT)events are among the most impact-related consequences related to climate change,especially for China,a nation with a large population that is vulnerable to the climate warming.Based on the latest Coupled Model Intercomparison Project Phase 6(CMIP6),this study assesses future EHT changes across China at five specific global warming thresholds(1.5℃-5℃).The results indicate that global mean temperature will increase by 1.5℃/2℃ before 2030/2050 relative to pre-industrial levels(1861-1900)under three future scenarios(SSP1-2.6,SSP2-4.5,and SSP5-8.5),and warming will occur faster under SSP5-8.5 compared to SSP1-2.6 and SSP2-4.5.Under SSP5-8.5,global warming will eventually exceed 5℃ by 2100,while under SSP1-2.6,it will stabilize around 2℃ after 2050.In China,most of the areas where warming exceeds global average levels will be located in Tibet and northern China(Northwest China,North China and Northeast China),covering 50%-70%of the country.Furthermore,about 0.19-0.44 billion people(accounting for 16%-41%of the national population)will experience warming above the global average.Compared to present-day(1995-2014),the warmest day(TXx)will increase most notably in northern China,while the number of warm days(TX90p)and warm spell duration indicator(WSDI)will increase most profoundly in southern China.For example,relative to the present-day,TXx will increase by 1℃-5℃ in northern China,and TX90p(WSDI)will increase by 25-150(10-80)days in southern China at 1.5℃-5℃ global warming.Compared to 2℃-5℃,limiting global warming to 1.5℃ will help avoid about 36%-87%of the EHT increases in China.