METTL14 regulates CD8+T-cell activation and immune responses to anti-PD-1 therapy in lung cancer.

BACKGROUND: N6-methyladenosine (m6A) modification plays an important role in lung cancer. However, methyltransferase-like 14 (METTL14), which serves as the main component of the m6A complex, has been less reported to be involved in the immune microenvironment of lung cancer. This study aimed to analyze the relationship between METTL14 and the immune checkpoint inhibitor programmed death receptor 1 (PD-1) in lung cancer. METHODS: CCK-8, colony formation, transwell, wound healing, and flow cytometry assays were performed to explore the role of METTL14 in lung cancer progression in vitro. Furthermore, syngeneic model mice were treated with sh-METTL14 andan anti-PD-1 antibody to observe the effect of METTL14 on immunotherapy. Flow cytometry and immunohistochemical (IHC) staining were used to detect CD8 expression. RIP and MeRIP were performed to assess the relationship between METTL14 and HSD17B6. LLC cells and activated mouse PBMCs were cocultured in vitro to mimic immune cell infiltration in the tumor microenvironment. ELISA was used to detect IFN-γ and TNF-α levels. RESULTS: The online database GEPIA showed that high METTL14 expression indicated a poor prognosis in patients with lung cancer. In vitro assays suggested that METTL14 knockdown suppressed lung cancer progression. In vivo assays revealed that METTL14 knockdown inhibited tumor growth and enhanced the response to PD-1 immunotherapy. Furthermore, METTL14 knockdown enhanced CD8+T-cell activation and infiltration. More importantly, METTL14 knockdown increased the stability of HSD17B6 mRNA by reducing its m6A methylation. In addition, HSD17B6 overexpression promoted the activation of CD8+ T cells. CONCLUSION: The disruption of METTL14 contributed to CD8+T-cell activation and the immunotherapy response to PD-1 via m6A modification of HSD17B6, thereby suppressing lung cancer progression.

First-Principles Investigation of Near-Surface Divacancies in Silicon Carbide.

The realization of quantum sensors using spin defects in semiconductors requires a thorough understanding of the physical properties of the defects in the proximity of surfaces. We report a study of the divacancy (VSiVC) in 3C-SiC, a promising material for quantum applications, as a function of surface reconstruction and termination with -H, -OH, -F and oxygen groups. We show that a VSiVC close to hydrogen-terminated (2 × 1) surfaces is a robust spin-defect with a triplet ground state and no surface states in the band gap and with small variations of many of its physical properties relative to the bulk, including the zero-phonon line and zero-field splitting. However, the Debye-Waller factor decreases in the vicinity of the surface and our calculations indicate it may be improved by strain-engineering. Overall our results show that the VSiVC close to SiC surfaces is a promising spin defect for quantum applications, similar to its bulk counterpart.

Hyperthermia promotes exosome secretion by regulating Rab7b while increasing drug sensitivity in adriamycin-resistant breast cancer.

PURPOSE: To investigate the mechanism through which hyperthermia promotes exosome secretion and drug sensitivity in adriamycin-resistant breast cancer. MATERIALS AND METHODS: We first evaluated the effect of hyperthermia on adriamycin-resistant breast cancer viability and used transmission electron microscopy, nanoparticle tracking analysis, and a bicinchoninic acid kit to validate the effect of hyperthermia on exosome secretion. The effective targeting molecules and pathways changed by hyperthermia were explored by RNA microarray and verified in vitro. The adriamycin-resistant MCF-7/ADR cells co-incubated with the exosomes produced by MCF-7/ADR cells after hyperthermia were assessed. The uptake of exosomes by MCF-7/ADR cells after hyperthermia treatment was evaluated by confocal microscopy. Finally, the mechanism through which hyperthermia promotes exosome secretion by hyperthermia was determined. RESULTS: Hyperthermia significantly suppressed the growth of adriamycin-resistant breast cancer cells and increased drug sensitivity by upregulating FOS and CREB5, genes related to longer overall survival in breast cancer patients. Moreover, hyperthermia promoted exosome secretion through Rab7b, a small GTPase that controls endosome transport. The upregulated FOS and CREB5 antioncogenes can be transferred to MCF-7/ADR cells by hyperthermia-treated MCF-7/ADR cell-secreted exosomes. CONCLUSIONS: Our results demonstrated a novel function of hyperthermia in promoting exosome secretion in adriamycin-resistant breast cancer cells and revealed the effects of hyperthermia on tumor cell biology. These hyperthermia-triggered exosomes can carry antitumor genes to the residual tumor and tumor microenvironment, which may be more beneficial to the effects of hyperthermia. These results represent an exploration of the relationship between therapeutic strategies and exosome biology.

Thickness-dependent ultrafast charge-carrier dynamics and coherent acoustic phonon oscillations in mechanically exfoliated PdSe2 flakes.

Recently, palladium diselenide (PdSe2) has emerged as a promising material with potential applications in electronic and optoelectronic devices due to its intriguing electronic and optical properties. The performance of the device is strongly dependent on the charge-carrier dynamics and the related hot phonon behavior. Here, we investigate the photoexcited-carrier dynamics and coherent acoustic phonon (CAP) oscillations in mechanically exfoliated PdSe2 flakes with a thickness ranging from 10.6 nm to 54 nm using time-resolved non-degenerate pump-probe transient reflection (TR) spectroscopy. The results imply that the CAP frequency is thickness-dependent. Polarization-resolved transient reflection (PRTR) measurements reveal the isotropic charge-carrier relaxation dynamics and the CAP frequency in the 10.6 nm region. In addition, the deformation potential (DP) mechanism dominates the generation of the CAP. Moreover, a sound velocity of 6.78 × 103 m s-1 is extracted from the variation of the oscillation period with the flake thickness and the delay time of the acoustic echo. These results provide insight into the ultrafast optical coherent acoustic phonon and optoelectronic properties of PdSe2 and may open new possibilities for PdSe2 applications in THz-frequency mechanical resonators.

Vertical distributions of wintertime atmospheric nitrogenous compounds and the corresponding OH radicals production in Leshan, southwest China.

Ground-based multi-axis differential optical absorption spectroscopy (MAX-DOAS) observations were operated from 02 to 21 December 2018 in Leshan, southwest China, to measure HONO, NO2 and aerosol extinction vertical distributions, and these were the first MAX-DOAS measurement results in Sichuan Basin. During the measurement period, characteristic ranges for surface concentration were found to be 0.26-4.58 km-1 and averaged at 0.93 km-1 for aerosol extinction, 0.49 to 35.2 ppb and averaged at 4.57 ppb for NO2 and 0.03 to 7.38 ppb and averaged at 1.05 ppb for HONO. Moreover, vertical profiles of aerosol, NO2 and HONO were retrieved from MAX-DOAS measurements using the Heidelberg Profile (HEIPRO) algorithm. By analysing the vertical gradients of pollutants and meteorological information, we found that aerosol and HONO are strongly localised, while NO2 is mainly transmitted from the north direction (city center direction). Nitrogen oxides such as HONO and NO2 are important for the production of hydroxyl radical (OH) and oxidative capacity in the troposphere. In this study, the averaged value of OH production rate from HONO is about 0.63 ppb/hr and maximum value of ratio between OH production from HONO and from (HONO+O3) is > 93% before12:00 in Leshan. In addition, combustion emission contributes to 26% for the source of HONO in Leshan, and we found that more NO2 being converted to HONO under the conditions with high aerosol extinction coefficient and high relative humidity is also a dominant factor for the secondary produce of HONO.

Significant changes in caecal microbial composition and metabolites of weaned piglets after protein restriction and succedent realimentation.

The present study aimed to investigate the effects of protein restriction and subsequent realimentation on caecal barrier function, caecal microbial composition and metabolites in weaned piglets. Thirty-six 28-day-old weaned piglets were randomly assigned to a control group and a treatment group. The piglets were fed diets containing 18.83% (normal) or 13.05% (low) of crude protein from the 1st to 14th day, after which all piglets were fed diets containing 18.83% of crude protein from the 15th to 28th day. The results showed that protein restriction increased caecal bacterial diversity and richness as well as the abundance of Ruminococcus 2, Faecalibacterium and Lachnospiraceae_uncultured, but reduced the abundance and the gene copies of Lactobacillus in the treatment group compared with the control group on day 14. Protein restriction also decreased the concentrations of isovaleric acid and total branched-chain fatty acids. During the succedent protein realimentation stage, the abundance of Ruminococcaceae UCG-014 and the concentrations of lactic acid, acetic acid, butyric acid and total short-chain fatty acids were increased in the treatment group on day 28. Furthermore, the ammonia concentration was reduced, while the gene mRNA levels of caecal barrier function were increased in the treatment group both on days 14 and 28. In conclusion, dietary protein restriction and realimentation could change caecal microbial composition and metabolites, and eventually influence caecal barrier function. The present study may provide a new insight into protein restriction and realimentation in weaned piglets.

Effects of early commercial milk supplement on the mucosal morphology, bacterial community and bacterial metabolites in jejunum of the pre- and post-weaning piglets.

OBJECTIVE: Sow milk (SM) may not be able to meet the piglet's nutritional needs in late lactation. Hence, this study was conducted to investigate the effects of early commercial milk (CM) supplement on the mucosal morphology, bacterial community and bacterial metabolites in jejunum of piglets. METHODS: Ten litters of newborn piglets ([Yorkshire×Landrace]×Duroc) were randomly divided into 2 groups of 5 litters. The piglets in the control group were suckled by the sow (SM), while the piglets in the treatment group (CM supplement) were supplemented with a CM supplement along with suckling from d 4 to d 28 of age. RESULTS: No significant differences were observed about jejunal mucosal morphology on d 28 and d 35 between two groups. On d 28, the activity of lactase in the jejunum was significantly decreased in the CM group, while the activity of sucrase and the ratio of maltase to lactase were significantly increased (p<0.05). On d 35, the activity of maltase in the jejunum was significantly increased in the CM group (p<0.05), and maltase to lactase ratio tended to increase in the CM group (p = 0.065). In addition, piglets in the CM group had a higher abundance of Clostridium XI, Tuicibater, and Moraxella in the jejunum on d 28, while the abundance of Lactobacillus was significantly increased on d 35 (p<0.05). CONCLUSION: The early CM supplement improved the maturation of the jejunum to some extent by enhancing the maltase and sucrase activities. Moreover, the early CM supplement could help maintain the homeostasis of internal environment in jejunum by increasing the microbial-derived metabolites.

The Changes of Colonic Bacterial Composition and Bacterial Metabolism Induced by an Early Food Introduction in a Neonatal Porcine Model.

The impact of an early food introduction on the microbiota composition and microbial metabolism in colon was investigated using a new-born piglet model. At day 4 after birth, 10 litters of piglets were randomly allocated to a sow-rearing group (SR group) and a milk-replacer supplementing group (MRS group) (n = 5). A commercial milk replacer was given to the suckling piglets in the MRS group from the 4th day to the 28th day. Pyrosequencing of the V3-V4 region of the 16S rRNA genes showed that the milk replacer supplementation significantly decreased the relative abundance of Lactobacillus, Clostridium XI, Blautia, Clostridium sensustricto and Escherichia (p = 0.08) in the colon of the piglets, but significantly increased the relative abundance of Paraprevotella on the 28th day. In addition, the abundance of Rumminococcus, Clostridium XlVa, Succiniclasticum, Clostridium IV tended to increase in the MRS group. The concentrations of acetate, propionate, butyrate, valerate and branch-chain fatty acids (BCFAs) in the colonic digesta increased with the milk replacer supplementary in the MRS group. In addition, the milk replacer supplementary increased the expression level of Toll-like receptor 4 (TLR4), but decreased the expression level of interleukin-6 (IL-6) in the colonic mucosa of the piglets. In conclusion, an early food introduction can influence the gut bacterial composition and metabolism, and may further affect the intestinal health by modifying the gene transcription related to the colonic function. These findings may provide some guidelines for the early nutrition supplementation for infants during the lactation period.

The long noncoding RNA urothelial carcinoma-associated 1 overexpression as a poor prognostic biomarker in clear cell renal cell carcinoma.

Long noncoding RNA urothelial carcinoma-associated 1 has previously played important roles in cancer. However, its role is still unknown in clear cell renal cell carcinoma. We utilized the most recent molecular and clinical data of clear cell renal cell carcinoma from The Cancer Genome Atlas project, and the relationship between urothelial carcinoma-associated 1 expression and the clinicopathological features was analyzed. Our results indicated that urothelial carcinoma-associated 1 overexpression was associated with male ( p = 0.003), wild-type PBRM1 ( p = 0.021), and BAP1 mutation ( p = 0.022) in clear cell renal cell carcinoma, although lower expression was found in tumors compared with normal controls, validated in tumor tissues from The Cancer Genome Atlas and 21 clear cell renal cell carcinoma patients at our hospital. Moreover, urothelial carcinoma-associated 1 overexpression indicated poor prognosis independently (Hazard Ratio [HR]: 1.92, p = 0.000) in clear cell renal cell carcinoma; it might be a potential detrimental gene considered as a predictive biomarker involved in clear cell renal cell carcinoma.

Surface Energy-Assisted Patterning of Vapor Deposited All-Inorganic Perovskite Arrays for Wearable Optoelectronics.

Solution-based methods for fabricating all-inorganic perovskite film arrays often suffer from limited control over nucleation and crystallization, resulting in poor homogeneity and coverage. To improve film quality, advanced vapor deposition techniques are employed for continuous film. Here, the vapor deposition strategy to the all-inorganic perovskite films array, enabling area-selective deposition of perovskite through substrate modulation is expanded. It can yield a high-quality perovskite film array with different pixel shapes, various perovskite compositions, and a high resolution of 423 dpi. The resulting photodetector arrays exhibit remarkable optoelectronic performance with an on/off ratio of 13 887 and responsivity of 47.5 A W-1. The device also displays long-term stability in a damp condition for up to 12 h. Moreover, a pulse monitoring sensor based on the perovskite films array demonstrates stable monitoring for pulse signals after being worn for 12 h and with a low illumination of 0.055 mW cm-2, highlighting the potential application in wearable optoelectronic devices.

Quantification and evaluation of atmospheric emissions from crop residue burning constrained by satellite observations in China during 2016-2020.

In rural regions of China, crop residue burning (CRB) is the major biomass burning activity, which can result in massive emissions of atmospheric particulate, greenhouse gas, and trace gas pollutants. Based on Himawari-8 satellite fire radiative power and agricultural statistics data, we implemented a daily inventory of agricultural fire emissions in 2016-2020 with a 2-km spatial resolution, including atmospheric pollutants such as CO2, CH4, CO, N2O, NOX, NH3, SO2, PM10, PM2.5, Hg, OC, EC, and NMVOCs. Our inventory constrained by geostationary satellite monitoring is more consistent with the actual CRB emissions in China, as many flaring events occur surreptitiously in the early morning and late evening to avoid regulation, which may be overlooked by polar-orbiting satellites. The spatiotemporal characterizations of various CRB emissions are found to be consistent with multiple satellite trace gas retrievals. We also assessed the effectiveness of field burning bans in China. Combined with other relevant datasets, it was found that although China has been advocating for a long time not to burn straw in the open field, CRB emissions was not successfully controlled nationwide until 2016. We estimated that the cumulative reduction of CO2 CRB emissions alone amounts to 809 ± 651 (2σ) teragram (Tg) during the 13th Five-Year Plan period (2016-2020), with an average value equivalent to 1.2 times the total annual territorial CO2 emissions by fossil fuels from Germany in 2021 (675 Tg, ranked 1st in EU27 and 7th in the world). Our inventory also suggests that continuous, long-term controls are necessary. Otherwise, CRB emissions may only be delayed on a seasonal scale, rather than reduced.

Vast ecosystem disturbance in a warming climate may jeopardize our climate goal of reducing CO2: a case study for megafires in the Australian 'black summer'.

A warming climate is one of the most important driving forces of intensified wildfires globally. The unprecedented wildfires broke out in the Australian 'Black Summer' (November 2019-February 2020), which released massive heat, gases, and particles into the atmosphere. The total carbon dioxide (CO2) emissions from wildfires were estimated at ∼963 million tons by using a top-down approach based on direct satellite measurements of CO2 and fire radiative power. The fire emissions have led to an approximately 50-80 folds increase in total CO2 emission in Australia compared with the similar seasons of 2014-2019. The excess CO2 from wildfires has offset almost half of the global anthropogenic CO2 emission reductions due to the Corona Virus Disease 2019 in 2020. When the wildfires were intense in December 2019, they caused a 1.48 watts per square meter additional positive radiative forcing above the monthly average in Australia and the vicinity. Our findings demonstrate that vast ecosystem disturbance in a warming climate can strongly influence the global carbon cycle and hamper our climate goal of reducing CO2.

A Universal Fabrication Strategy for High-Resolution Perovskite-Based Photodetector Arrays.

Metal halide perovskite photodetector arrays have demonstrated great potential applications in the field of integrated systems, optical communications, and health monitoring. However, the fabrication of large-scale and high-resolution device is still challenging due to their incompatibility with the polar solvents. Here, a universal fabrication strategy that utilizes ultrathin encapsulation-assisted photolithography and etching to create high-resolution photodetectors array with vertical crossbar structure is reported. This approach yields a 48 × 48 photodetector array with a resolution of 317 ppi. The device shows good imaging capability with a high on/off ratio of 3.3 × 105 and long-term working stability over 12 h. Furthermore, this strategy can be applied to five different material systems, and is fully compatible with the existing photolithography and etching techniques, which are expected to have potential applications in the other high-density and solvent-sensitive devices array, including perovskite- or organic semiconductor-based memristor, light emitting diode displays, and transistors.

Atomic-level chemical reaction promoting external quantum efficiency of organic photomultiplication photodetector exceeding 108% for weak-light detection.

Low-cost, solution-processed photomultiplication organic photodetectors (PM-OPDs) with external quantum efficiency (EQE) above unity have attracted enormous attention. However, their weak-light detection is unpleasant because the anode Ohmic contact causes exacerbation in dark current. Here, we introduce atomic-level chemical reaction in PM-OPDs which can simultaneously suppress dark current and increase EQE via depositing a 0.8 nm thick Al2O3 by the atomic layer deposition. Suppression in dark current mainly originates from the built-in anode Schottky junction as a result of work function decrease of hole-transporting layer of which the chemical groups can react chemically with the bottom surface of Al2O3 layer at the atomic-level. Such strategy of suppressing dark current is not adverse to charge injection under illumination; instead, responsivity enhancement is realized because charge injection can shift from cathode to anode, of which the neighborhood possesses increased photogenerated carriers. Consequently, weak-light detection limit of the forwardly-biased PM-OPD with Al2O3 treatment reaches a remarkable level of 2.5 nW cm-2, while that of the reversely-biased control is 25 times inferior. Meanwhile, the PM-OPD yields a record high EQE and responsivity of 4.31 × 108% and 1.85 × 106 A W-1, respectively, outperforming all other polymer-based PM-OPDs.

Effects of Protein Restriction and Succedent Realimentation on Jejunal Function and Bacterial Composition of Different Colonic Niches in Weaned Piglets.

Recent studies have proved that protein succedent realimentation could rescue the loss of growth performance in weaning piglets caused by a prior protein restriction. However, how the protein restriction and succedent realimentation influence the jejunal function and bacterial composition of different colonic niches microbiota in weaning piglets needs a further investigation. After protein succedent realimentation, we found that the treatment group (TRE) piglets had a higher IGF-1 content and IGF-1R gene expression level in jejunal mucosa than the control group (CON) piglets. The ZO-1 gene expression level was up-regulated in the jejunal mucosa of TRE piglets during protein restriction and succedent realimentation, while the jejunal permeability of TRE piglets was only decreased after protein succedent realimentation. In addition, we found that protein restriction and succedent realimentation increased the gene expression of Pept-1 and the fecal apparent digestibility of crude protein in TRE piglets, but decreased the fecal nitrogen content. After 16S rRNA MiSeq sequencing of bacteria in different colonic niches (mucosa and digesta), TRE piglets had a higher relative abundance of beneficial bacteria and a lower relative abundance of potential pathogens than CON piglets in different colonic niches after protein restriction and succedent realimentation. Our data showed that protein restriction and succedent realimentation decreased the concentrations of branch chain fatty acids and ammonia-N in the colon of TRE piglets. In addition, protein succedent realimentation increased the concentration of total short chain fatty acids in the colon of TRE piglets. All these findings demonstrated that the strategy of protein restriction and succedent realimentation is an effective way to improve intestinal health of weaning piglets, and provided new insights into the nutrition management of piglets during the weaning period.

Impacts of TROPOMI-Derived NO X Emissions on NO2 and O3 Simulations in the NCP during COVID-19.

NO2 and O3 simulations have great uncertainties during the COVID-19 epidemic, but their biases and spatial distributions can be improved with NO2 assimilations. This study adopted two top-down NO X inversions and estimated their impacts on NO2 and O3 simulation for three periods: the normal operation period (P1), the epidemic lockdown period following the Spring Festival (P2), and back to work period (P3) in the North China Plain (NCP). Two TROPOspheric Monitoring Instrument (TROPOMI) NO2 retrievals came from the Royal Netherlands Meteorological Institute (KNMI) and the University of Science and Technology of China (USTC), respectively. Compared to the prior NO X emissions, the two TROPOMI posteriors greatly reduced the biases between simulations with in situ measurements (NO2 MREs: prior 85%, KNMI -27%, USTC -15%; O3 MREs: Prior -39%, KNMI 18%, USTC 11%). The NO X budgets from the USTC posterior were 17-31% higher than those from the KNMI one. Consequently, surface NO2 levels constrained by USTC-TROPOMI were 9-20% higher than those by the KNMI one, and O3 is 6-12% lower. Moreover, USTC posterior simulations showed more significant changes in adjacent periods (surface NO2: P2 vs P1, -46%, P3 vs P2, +25%; surface O3: P2 vs P1, +75%, P3 vs P2, +18%) than the KNMI one. For the transport flux in Beijing (BJ), the O3 flux differed by 5-6% between the two posteriori simulations, but the difference of NO2 flux between P2 and P3 was significant, where the USTC posterior NO2 flux was 1.5-2 times higher than the KNMI one. Overall, our results highlight the discrepancies in NO2 and O3 simulations constrained by two TROPOMI products and demonstrate that the USTC posterior has lower bias in the NCP during COVD-19.

Vertical profiles of the transport fluxes of aerosol and its precursors between Beijing and its southwest cities.

The influence of regional transport on aerosol pollution has been explored in previous studies based on numerical simulation or surface observation. Nevertheless, owing to inhomogeneous vertical distribution of air pollutants, vertical observations should be conducted for a comprehensive understanding of regional transport. Here we obtained the vertical profiles of aerosol and its precursors using ground-based multi-axis differential optical absorption spectroscopy (MAX-DOAS) at the Nancheng site in suburban Beijing on the southwest transport pathway of the Beijing-Tianjin-Hebei (BTH) region, China, and then estimated the vertical profiles of transport fluxes in the southwest-northeast direction. The maximum net transport fluxes per unit cross-sectional area, calculated as pollutant concentration multiply by wind speed, of aerosol extinction coefficient (AEC), NO2, SO2 and HCHO were 0.98 km-1 m s-1, 24, 14 and 8.0 µg m-2 s-1 from southwest to northeast, which occurred in the 200-300 m, 100-200 m, 500-600 m and 500-600 m layers, respectively, due to much higher pollutant concentrations during southwest transport than during northeast transport in these layers. The average net column transport fluxes were 1200 km-1 m2 s-1, 38, 26 and 15 mg m-1 s-1 from southwest to northeast for AEC, NO2, SO2 and HCHO, respectively, in which the fluxes in the surface layer (0-100 m) accounted for only 2.3%-4.2%. Evaluation only based on surface observation would underestimate the influence of the transport from southwest cities to Beijing. Northeast or weak southwest transports dominated in clean conditions with PM2.5 <75 µg m-3 and intense southwest transport dominated in polluted conditions with PM2.5 >75 µg m-3. Southwest transport through the middle boundary layer was a trigger factor for aerosol pollution events in urban Beijing, because it not only directly bringing air pollutants, but also induced an inverse structure of aerosols, which resulted in stronger atmospheric stability and aggravated air pollution in urban Beijing.

Five-second coherence of a single spin with single-shot readout in silicon carbide.

An outstanding hurdle for defect spin qubits in silicon carbide (SiC) is single-shot readout, a deterministic measurement of the quantum state. Here, we demonstrate single-shot readout of single defects in SiC via spin-to-charge conversion, whereby the defect's spin state is mapped onto a long-lived charge state. With this technique, we achieve over 80% readout fidelity without pre- or postselection, resulting in a high signal-to-noise ratio that enables us to measure long spin coherence times. Combined with pulsed dynamical decoupling sequences in an isotopically purified host material, we report single-spin T2 > 5 seconds, over two orders of magnitude greater than previously reported in this system. The mapping of these coherent spin states onto single charges unlocks both single-shot readout for scalable quantum nodes and opportunities for electrical readout via integration with semiconductor devices.

Inhomogeneous Trap-State-Mediated Ultrafast Photocarrier Dynamics in CsPbBr3 Microplates.

Quantitatively elucidating photocarrier dynamics mediated by trap states in perovskites is crucial for establishing a structure-performance relation and understanding the interfacial photocarrier transport mechanism. Here, trap-state-mediated photocarrier dynamics in defect-rich CsPbBr3 microplates are noninvasively investigated by ultrafast laser spectroscopy. Time-resolved photoluminescense (TRPL) measurements as a function of sample thickness indicate that trap densities of surface and bulk regions are inhomogeneous, leading to fast and slow decay components of TRPL, respectively. Fast and slow PL lifetimes present the same decreasing trend as the thickness is decreased from 5 to 0.1 µm, suggesting that both surface and bulk trap densities dramatically increase in sub-micrometer thick microplates. Furthermore, dynamical competition of ultrafast photocarrier energy relaxations between surface and bulk regions is studied in a 1.6 µm-thick sample by temporally correlating pump fluence-dependent TRPL with transient absorption signals. Strikingly, long-lived hot carriers (20 ps) are observed and complete filling of mid-gap trap states in the surface region can markedly enhance PL emission in the bulk region. By control measurements, we attribute these anomalous phenomena to the polaron-assisted ultrafast energy transfer process across the surface-bulk interface. Our results provide new insights into dynamical photocarrier energy relaxations and interfacial energy transport for inorganic perovskites.

Exosomal miR-222 from adriamycin-resistant MCF-7 breast cancer cells promote macrophages M2 polarization via PTEN/Akt to induce tumor progression.

Exosome-mediated intercellular communication is considered to be an effective mode for malignant cells to transform biological behaviors in stromal cells. However, the mechanisms by which exosomes modulate macrophages within tumor microenvironment remain largely unclear. In this study, we found that both adriamycin-resistant breast cancer (BCa) cells and the corresponding exosomes (A/exo) were capable of inducing macrophages M2 polarization, which promoted the mobility, proliferation, migration and invasion of BCa cells. Since exosomes deliver microRNAs to affect cellular functions in recipient cells, we confirmed that miR-222 was significantly enriched in A/exo and could be successfully transferred to macrophages. Increased miR-222 level was also detected in exosomes derived from plasma and tissues of chemoresistant patients. Moreover, exosomal miR-222 from A/exo polarized M2 macrophages by targeting PTEN and activating Akt signaling pathway, which promoted BCa cells progression in a feed back loop. Co-culture of adriamycin-resistant BCa cells with macrophages in which miR-222 was upregulated or treated with A/exo facilitated tumor growth in vivo. Collectively, our data demonstrated that chemoresistant BCa cells could remodel macrophages within tumor microenvironment by secreting exosomal miR-222, which directly targeted PTEN and caused Akt cascade activation and macrophages M2 polarization. Our findings may provide a foundation for a promising strategy of BCa treatment by targeting exosomes or exosomal miR-222.