Regulation of N6-methyladenosine modification in erythropoiesis and thalassemia.

In eukaryotic RNA, N6-methyladenosine (m6A) is a prevalent form of methylation modification. The m6A modification process is reversible and dynamic, written by m6A methyltransferase complex, erased by m6A demethylase, and recognized by m6A binding proteins. Through mediating RNA stability, decay, alternative splicing, and translation processes, m6A modification regulates gene expression at the post-transcriptional level. Erythropoiesis is the process of hematopoietic stem cells undergoing proliferation, a series of differentiation and maturation to form red blood cells (RBCs). Thalassemia is a common monogenic disease characterized by excessive production of ineffective RBCs in the peripheral circulation, resulting in hemolytic anemia. Increasing evidence suggests that m6A modification plays a crucial role in erythropoiesis. In this review, we comprehensively summarize the function of m6A modification in erythropoiesis and further generalize the mechanism of m6A modification regulating ineffective erythropoiesis and fetal hemoglobin expression. The purpose is to improve the understanding of the pathogenesis of erythroid dysplasia and offer new perspectives for the diagnosis and treatment of thalassemia.

The interactions between ineffective erythropoiesis and ferroptosis in ß-thalassemia.

In Guangxi, Hainan, and Fujian Province in southern China, ß-thalassemia is a frequent monogenic hereditary disorder that is primarily defined by hemolytic anemia brought on by inefficient erythropoiesis. It has been found that ineffective erythropoiesis in ß-thalassemia is closely associated with a high accumulation of Reactive oxygen species, a product of oxidative stress, in erythroid cells. During recent years, ferroptosis is an iron-dependent lipid peroxidation that involves abnormalities in lipid and iron metabolism as well as reactive oxygen species homeostasis. It is a recently identified kind of programmed cell death. ß-thalassemia patients experience increased iron release from reticuloendothelial cells and intestinal absorption of iron, ultimately resulting in iron overload. Additionally, the secretion of Hepcidin is inhibited in these patients. What counts is both ineffective erythropoiesis and ferroptosis in ß-thalassemia are intricately linked to the iron metabolism and Reactive oxygen species homeostasis. Consequently, to shed further light on the pathophysiology of ß-thalassemia and propose fresh ideas for its therapy, this paper reviews ferroptosis, ineffective erythropoiesis, and the way they interact.

Recent Advances in Smart Windows Based on Photo-Responsive Liquid Crystals Featuring Phase Transition.

A smart window is an optical dimming device with intelligent functions that can control its relevant performances through external stimuli, achieving functions such as privacy protection and temperature regulation. Light is an ideal stimulus for regulating smart windows, which is noninvasive and allows self-adaptable manipulation of materials. This review highlights recent significant achievements in smart windows constructed by photo-responsive liquid crystals (LCs) systems that can undergo the transition between different phases. The smart windows based on photo-responsive LCs are used in a plethora of areas, including privacy protection, absorption glass, building decoration, energy saving, and climate modulation applications. The review concludes with a brief perspective on some significant challenges and opportunities for the future development of photo-responsive smart windows, which is crucial for expanding the applications of smart windows and improving their performances.

Association of triglyceride-glucose index trajectory and frailty in urban older residents: evidence from the 10-year follow-up in a cohort study.

BACKGROUND: Frailty is an age-related geriatric syndrome that leads to a series of clinically negative events. A better understanding of the factors associated with frailty assists in preventing its progression. The triglyceride-glucose (TyG) index, a simple alternative index of insulin resistance, has not yet been proven to be associated with frailty. The present study aimed to investigate the association between the TyG index and its trajectory with frailty from a cross-sectional, retrospective and prospective level based on an ongoing cohort. METHODS: This longitudinal study included 1,866 older residents from the "Fujian prospective aging cohort" (ChiCTR 2,000,032,949). The TyG index was calculated as ln [fasting triglyceride (mg/dL) ╳ fasting plasma glucose (mg/dL)/2] and group-based trajectory model (GBTM) was applied to identify the trajectory of TyG index. The association between different trajectory groups of TyG index with frailty risk were estimated using multinomial logistic regression analysis. RESULTS: In the cross-sectional analysis, the highest quartile of the TyG index was associated with an increased risk of frailty (TyG index Q4 vs. Q1, OR = 1.50, 95% CI 1.00-2.25, P = 0.048). Restricted cubic splines demonstrated an increasing trend for TyG index and frailty risk. During a follow-up of ten years, three distinct trajectories of the TyG index were identified: low-stable (n = 697, 38.3%), moderate-stable (n = 910, 50.0%) and high-stable (n = 214, 11.7%). Compared with those in the stable-low group of TyG index trajectory, the ORs (95% CI) of prefrailty and frailty risk were 1.79 (95% CI 1.11-2.88) and 2.17 (95% CI 1.01-3.88) for the high-stable group, respectively (P = 0.017 and P = 0.038). In the subgroup analysis, the association of the high-stable trajectory of TyG and frailty status were only observed in subjects with BMI ≥ 24 kg/m2. Prospectively, the highest quartile of the TyG index was associated with a 2.09-fold significantly increased risk of one-year ADL/IADL decline (P = 0.045). CONCLUSIONS: The present study suggests a potential role for a high and sustainable level of TyG index in the risk of frailty. The trajectories of the TyG index can help to identify older individuals at a higher risk of frailty who deserve primitive preventive and therapeutic approaches.

Pericyte Dysfunction Contributes to Vascular Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats.

Vascular cognitive impairment (VCI) encompasses cognitive disorders associated with cerebrovascular disease, often manifesting as white matter lesions (WMLs), irrespective of precise triggers. The integrity of white matter is essential for neural communication and cognitive function maintenance. Persistent cerebral hypoperfusion-induced WMLs are now acknowledged as a key driver of VCI and dementia, though their exact formation mechanism remains unclear. Recent studies link pericyte dysfunction to diverse brain disorders like Alzheimer disease. However, the exact pathological connection between pericyte dysfunction and cognitive impairment in VCI remains unexplored. In this study, we aimed to examine whether pericyte dysfunction could impact WMLs and cognitive impairment in a rat VCI model. Using a rat model of chronic cerebral hypoperfusion-induced VCI through two-vessel occlusion (2VO), we verified that 2VO induced both WMLs and cognitive impairment. Notably, the number of pericytes in the brain was significantly altered after 2VO. Furthermore, we observed significantly increased capillary constrictions at pericyte bodies in the brains of 2VO-induced rats compared to sham-operated rats, accompanied by reduced cerebral blood flow (CBF). To tackle this issue, we administered CGS21680, a specific adenosine A2A subtype receptor agonist, intranasally twice a day for 7 days. We found that rats treated with CGS21680 exhibited a significant increase in CBF at 7 and 14 days after 2VO, compared to the vehicle group. Moreover, capillary lumens beneath pericytes also increased after the CGS21680 treatment. Importantly, the treatment led to substantial improvements in WMLs and cognitive impairment compared to the vehicle group. Our findings suggest a critical role of pericyte dysfunction in WMLs and cognitive impairment within the rat VCI model. This insight contributes to our understanding of pathogenesis and offers prospects for targeted intervention in VCI.

A Photo- and Thermo-Driven Azoarene-Based Circularly Polarized Luminescence Molecular Switch in a Liquid Crystal Host.

The development of chiral optical active materials with switchable circularly polarized luminescence (CPL) signals remains a challenge. Here an azoarene-based circularly polarized luminescence molecular switch, (S, R, S)-switch 1 and (R, R, R)-switch 2, are designed and prepared with an (R)-binaphthyl azo group as a chiral photosensitive moiety and two (S)- or (R)-binaphthyl fluorescent molecules with opposite or the same handedness as chiral fluorescent moieties. Both switches exhibit reversible trans/cis isomerization when irradiated by 365 nm UV light and 520 nm green light in solvent and liquid crystal (LC) media. In contrast with the control (R, R, R)-switch 2, when switch 1 is doped into nematic LCs, polarization inversion and switching-off of the CPL signals are achieved in the resultant helical superstructure upon irradiation with 365 nm UV and 520 nm green light, respectively. Meanwhile, the fluorescence intensity of the system is basically unchanged during this switching process. In particular, these variations of the CPL signals could be recovered after heating, realizing the true sense of CPL reversible switching. Taking advantage of the unique CPL switching, the proof-of-concept for "a dual-optical information encryption system" based on the above CPL active material is demonstrated.

Polymer-Stabilized Liquid Crystal Films Containing Dithienyldicyanoethene-Based Chiral Photoswitch: Multi-Modulation for Environment-Adaptative Smart Windows.

A polymer-stabilized liquid crystal (PSLC)-based environment-adaptative smart window with multi-modulations is demonstrated. This PSLC system contains a right-handed dithienyldicyanoethene-based chiral photoswitch and a chiral dopant, S811, with opposite handedness, of which the reversible cis-trans photoisomerization of the switch can drive self-shading of the smart window under UV light stimulus because of the transition from nematic phase to cholesteric one. With the assistance of solar heat, the opacity of the smart window can be deepened because the heat promotes the isomerization conversion rate of the switch. This switch has no thermal relaxation at room temperature, therefore, the smart window exhibits dual stabilization: transparent state (cis-isomer) and opaque state (trans-isomer). Moreover, the incident intensity of sunlight can be regulated by an electric field, which allows the smart window to adapt to some specific situations. Such an energy-saving device can be used in buildings and vehicles to control indoor temperature and adapt to the required ambiance.

Photo-triggered full-color circularly polarized luminescence based on photonic capsules for multilevel information encryption.

Materials with phototunable full-color circularly polarized luminescence (CPL) have a large storage density, high-security level, and enormous prospects in the field of information encryption and decryption. In this work, device-friendly solid films with color tunability are prepared by constructing Förster resonance energy transfer (FRET) platforms with chiral donors and achiral molecular switches in liquid crystal photonic capsules (LCPCs). These LCPCs exhibit photoswitchable CPL from initial blue emission to RGB trichromatic signals under UV irradiation due to the synergistic effect of energy and chirality transfer and show strong time dependence because of the different FRET efficiencies at each time node. Based on these phototunable CPL and time response characteristics, the concept of multilevel data encryption by using LCPC films is demonstrated.

Dietary diversity and overweight are associated with high intrinsic capacity among Chinese urban older adults (2020-2021).

BACKGROUND AND OBJECTIVES: The associations of intrinsic capacity (IC) with dietary diversity and body mass index (BMI) remain unclear in older adults. This study aimed to examine the associations of dietary diversity and BMI on high IC. METHODS: The cross-sectional study used data from the Fujian Prospective Aging Cohort, which included 1972 individuals aged 60-98 from 2020 to 2021. The dietary diversity score (DDS) was constructed with eight food varieties, and consuming ≥five varieties of food daily was considered a high DDS. BMI was grouped into underweight, normal weight, overweight, and obesity according to the Chinese guidelines. High IC was defined as ≥three unimpaired domains of cognition, locomotion, sensory, vitality, and psychology. RESULTS: Multivariate logistic regression analysis was used to assess the separate association of high DDS and BMI groups with high IC. Compared with low DDS, high DDS had a positive association with high IC (OR = 1.42, 95 % CI = 1.16-1.74). Compared with normal weight, underweight was inversely related to high IC (OR = 0.18, 95 % CI = 0.09-0.36), overweight was positively related to high IC (OR = 1.65, 95 % CI = 1.33-2.06), while no significant association was observed between obesity and high IC. The restricted cubic spline model exhibited an inverted U-shaped nonlinear curve of BMI and high IC and identified an optimal BMI of 25.7 kg/m2 for high IC. CONCLUSIONS: High DDS is a protective factor of high IC in older adults. Overweight had the most protective association with high IC among the four BMI subgroups. Individuals with overweight and higher dietary diversity had higher IC.

The identification and prediction of frailty based on Bayesian network analysis in a community-dwelling older population.

BACKGROUND: We have witnessed frailty, which characterized by a decline in physiological reserves, become a major public health issue in older adults. Understanding the influential factors associated with frailty may help prevent or if possible reverse frailty. The present study aimed to investigate factors associated with frailty status and frailty transition in a community-dwelling older population. METHODS: A prospective cohort study on community-dwelling subjects aged ≥ 60 years was conducted, which was registered beforehand (ChiCTR 2,000,032,949). Participants who had completed two visits during 2020-2021 were included. Frailty status was evaluated using the Fried frailty phenotype. The least absolute shrinkage and selection operator (LASSO) regression was applied for variable selection. Bayesian network analysis with the max-min hill-climbing (MMHC) algorithm was used to identify factors related to frailty status and frailty transition. RESULTS: Of 1,981 subjects at baseline, 1,040 (52.5%) and 165 (8.33%) were classified as prefrailty and frailty. After one year, improved, stable, and worsening frailty status was observed in 460 (35.6%), 526 (40.7%), and 306 (23.7%) subjects, respectively. Based on the variables screened by LASSO regression, the Bayesian network structure suggested that age, nutritional status, instrumental activities of daily living (IADL), balance capacity, and social support were directly related to frailty status. The probability of developing frailty is 14.4% in an individual aged ≥ 71 years, which increases to 20.2% and 53.2% if the individual has balance impairment alone, or combined with IADL disability and malnutrition. At a longitudinal level, ADL/IADL decline was a direct predictor of worsening in frailty state, which further increased the risk of hospitalization. Low high-density lipoprotein cholesterol (HDL-C) and diastolic blood pressure (DBP) levels were related to malnutrition, and further had impacts on ADL/IADL decline, and ultimately led to the worsening of the frailty state. Knowing the status of any one or more of these factors can be used to infer the risk of frailty based on conditional probabilities. CONCLUSION: Older age, malnutrition, IADL disability, and balance impairment are important factors for identifying frailty. Malnutrition and ADL/IADL decline further predict worsening of the frailty state.

Handgrip strength weakness and asymmetry together are associated with cardiovascular outcomes in older outpatients: A prospective cohort study.

AIM: The evaluations of handgrip strength (HGS) weakness and asymmetry have implications for the comprehensive geriatric assessment. The aim of this study was to investigate the association of HGS weakness and asymmetry on cardiovascular outcomes in older outpatients. METHODS: This was a prospective observational cohort study of 364 Geriatrics outpatients aged ≥60 years, in which all participants carried out HGS tests at baseline. Patients with HGS <28 kg for men and <18 kg for women were diagnosed as HGS weakness, and HGS ratio <0.90 or >1.10 were diagnosed as HGS asymmetry. Primary outcomes defined as the major adverse cardiovascular event and composite end-points were assessed during a 21-month median follow-up. RESULTS: Among 364 participants, 155 (42.6%) showed HGS weakness, and 160 (44.0%) showed HGS asymmetry. HGS weakness was associated with major adverse cardiovascular events (HR 2.76, 95% CI 1.22-6.27) and composite end-points (HR 2.84, 95% CI 1.40-5.77). However, no significant correlation between HGS asymmetry and cardiovascular outcomes was observed. Compared with the normal and symmetric HGS group, older adults with HGS weakness and asymmetry together had a higher risk of major adverse cardiovascular events (HR 5.23, 95% CI 1.56-17.54) and composite end-points (HR 4.00, 95% CI 1.56-10.28). CONCLUSIONS: HGS weakness and asymmetry together might increase the risk of cardiovascular outcomes in older outpatients. HGS asymmetry offers complementary information to HGS weakness when making a comprehensive assessment of HGS. Geriatr Gerontol Int 2022; 22: 759-765.

Intrinsic Capacity Declines with Elevated Homocysteine in Community-Dwelling Chinese Older Adults.

Purpose: Intrinsic capacity (IC) reflects the overall health status of older adults and has great public health significance. But few studies described the related biomarkers for IC. The aim of this study was to investigate the association between homocysteine (Hcy) and IC in older adults. Participants and Methods: This cross-sectional study included 1927 community-dwelling Chinese older adults aged 60-98 years from May 2020 to December 2020. Data were collected through interviews, physical examinations, and laboratory tests. IC involved five domains of cognition, locomotion, sensory, vitality, and psychology evaluated by the Mini-cog scale, 4-m walk test, self-reported visual and hearing conditions, MNA-SF scale, and GDS-4 scale, respectively. The score of each domain dichotomized as 0 (normal) and 1 (impaired) was added together to an IC total score. Low IC was defined as a score of 3-5, and high IC as 0-2. Hcy was measured by a two-reagent enzymatic assay. A restricted cubic spline regression model was used to explore the non-linear relationship between Hcy and low IC. Results: Hcy was higher in the low IC group than in the high IC group. Restricted cubic spline analysis revealed a J-shaped nonlinear association between Hcy and low IC. The risk of IC decline was slowly decreased until 8.53 µmol/L of Hcy (OR=0.753, 95% CI=0.520-1.091, P=0.132), and increased with elevations of per 5 µmol/L Hcy afterwards (OR=1.176, 95% CI=1.059-1.327, P=0.005). Among the five domains of IC, Hcy had ORs of 1.116 (1.009-1.247) for cognition impairment, 1.167 (1.055-1.305) for vitality, and 1.160 (1.034-1.303) for psychology per 5 µmol/L increase in Hcy above the change point. Additional sensitivity analysis also demonstrated the nonlinear association between Hcy and low IC. Conclusion: Hcy had a J-shaped association with low IC. Higher Hcy (Hcy ≥8.53µmol/L) might provide clinical implications for early identifying the risk of low IC.

Examining the independent and interactive association of physical activity and sedentary behaviour with frailty in Chinese community-dwelling older adults.

BACKGROUND: While physical inactivity or prolonged sitting has been linked to an increased risk of frailty, the interaction between sitting time (ST), physical activity (PA) and frailty is not well understood. The aim of this study was to examine the dose-response relationship between PA, ST and frailty and further to evaluate the interaction effect of PA and ST on frailty in the context of regular COVID-19 epidemic prevention and control in China. METHODS: A cross-sectional analysis was performed on 1458 participants (age ≥ 60) enrolled from a prospective cohort study of frailty in elderly people of Fujian Province. PA and ST levels were assessed using the International Physical Activity Questionnaire. A 40-item frailty index (FI) quantified frailty. Multivariable logistic regression and linear regression models were applied to examine the dose-response relationship between PA or ST and frailty level. Interaction plots were used to visualise the interaction effects of PA and ST on frailty. RESULTS: Compared with light PA, the odds ratios (ORs) for frailty were significantly lower for moderate PA (OR, 0.609 [95% CI, 0.419, 0.885], P < .001) and vigorous PA (OR, 0.399 [95% CI, 0.236,0.673], P < .001). Comparing subjects with ST <  4 h/day, those with ST ≥ 8 h/day were significantly more likely to be diagnosed with frailty (OR, 3.140 [95% CI, 1.932, 5.106], P < .001), 6-8 h/day (OR, 1.289 [95% CI, 0.835, 1.989], P >0.05), and 4-6 h/day (OR, 1.400 [95% CI, 0.972, 2.018], P >0.05). Each one unit increase in metabolic equivalents (h/day) of PA was related to an average 0.928 (0.887, 0.971) decrease in prevalence of frailty, while each one unit increase in sitting time (h/day) was related to average 1.114 (1.046,1.185) increase in prevalence of frailty. Negative interactive effects of PA and ST on frailty were observed (P < 0.001). CONCLUSION: There are nonlinear and linear dose-response relationships between PA, SB and frailty respectively. In addition, excess ST may counteract the beneficial effects of PA on frailty. Interventions that focus on reducing excess ST may be effective strategies to reduce the risk of frailty and should be taken seriously by public health authorities, especially in the context of regular epidemic prevention and control in China.

Turn-On Mode Circularly Polarized Luminescence in Self-Organized Cholesteric Superstructure for Active Photonic Applications.

Developing circularly polarized luminescence (CPL)-active materials with a large luminescence dissymmetry factor (glum) or stimulus responses has evoked a lot of interest in the past few years; however, the light-controllable "on/off" CPL still remains a challenge. Here, a novel diarylethene-based chiral fluorescent photoswitch featuring "turn-on" CPL characteristic is developed, designated as (S,S)-switch 6, which can undergo reversible photocyclization/cycloreversion upon irradiation with UV and visible light. (S,S)-Switch 6 shows completely reversible "off-on-off"-responsive CPL behavior in solution. By doping (S,S)-switch 6 into nematic liquid crystals (LCs), the consequent luminescent cholesteric LCs (CLCs) exhibit a larger glum value enhanced 2 orders of magnitude when irradiated with UV light, which can be attributed to the highly ordered helical arrangement of CLCs. The potentials of this turn-on type CPL material for anticounterfeiting and information encryption are illustrated. Furthermore, the visualization of circularly polarized (CP) fluorescent patterns can be successfully achieved by constructing the double-layer CPL system consisting of a CP luminescent layer and a polymer cholesteric reflective layer. The proposed concept establishes a light-controlled off-on-off CPL platform that is of tremendous potential for applications in multi-informational data storage and encryption devices.

Modifiable predictive factors and all-cause mortality in the non-hospitalized elderly population: An umbrella review of meta-analyses.

OBJECTIVE: This umbrella review aimed to summarize the association between modifiable predictive factors and all-cause mortality in the non-hospitalized elderly population, and estimated the credibility and strength of the current evidence. METHODS: PubMed, Embase, Web of science, and EBSCOhost were searched up to February 28, 2022. Random-effect summary effect sizes and 95% confidence intervals (CIs), heterogeneity, small-study effect, excess significance bias, as well as 95% prediction intervals (PIs) were calculated. Methodological quality was assessed with the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool. The credibility of the included meta-analyses was graded from convincing to weak using established criteria. This umbrella review was registered with PROSPERO, CRD 42021282183. RESULTS: In total, 32 predictive factors involving 49 associations extracted from 35 meta-analyses were analyzed. Forty-three of the 49 (87.8%) associations presented nominal significant effects by the random-effect model (P < 0.05), of which 34 had harmful associations and nine had beneficial associations with all-cause mortality. Frailty (FRAIL scale), low short physical performance battery (SPPB) score, and fewer daily steps carried a more than three-fold risk for all-cause mortality. Convincing evidence showed that weight fluctuation, prefrailty and frailty status, sarcopenia, low SPPB score, fewer daily steps, and fatigue increased the risk of all-cause mortality, while daily moderate-to-vigorous physical activity (MVPA) duration and total physical activity participation reduced the risk of death. There were twenty, nine, five, and six associations that yielded highly suggestive, suggestive, weak, and non-significant grades of evidence. Thirty-four (69.4%) of the associations exhibited significant heterogeneity. Twenty-two associations presented 95% PIs excluding the null value, two indicated small-study effects, and three had evidence for excess significance bias, respectively. The methodological quality of most meta-analyses was rated as low (37.1%) or critically low (42.9%). CONCLUSIONS: A summary of the currently available meta-analyses suggests that a broad range of modifiable predictive factors are significantly associated with all-cause mortality risk in the non-hospitalized elderly population. The most credible evidence indicates that physical function represented by frailty and sarcopenia, as well as physical activity, are significant predictors for all-cause mortality. This umbrella review may provide prognostic information to direct appropriate diagnostic evaluation and treatment goals in the future. More solid evidence is still needed coming from moderate-to-high quality meta-analyses.

Circulating Pro-Inflammatory Exosomes Worsen Stroke Outcomes in Aging.

[Figure: see text].

Near-infrared light-induced photoisomerization and photodissociation of a chiral fluorescent photoswitch in cholesteric liquid crystals assisted by upconversion nanoparticles.

Upconversion-luminescence-induced reflective color switching and fluorescence tuning of a cholesteric liquid crystal (CLC) cells were investigated. The CLC system was constructed by co-doping a chiral fluorescence photoswitch, switch 5, and upconversion nanoparticles (UCNPs) into nematic LC media. Under irradiation with 980 nm NIR light, the UCNPs emit both 450 nm blue light and 365 nm UV light to induce the simultaneous Z-to-E and E-to-Z photoisomerization of switch 5. This continuous rotation-inversion movement further leads to an irreversible photoisomerization and photodissociation of dicyanodistyrylthiophene moieties in switch 5. As a result, the reflective color of the CLC cell changed from blue to red and the fluorescence intensity decreased as well when exposed to 980 nm NIR light. Finally, optically written reflective-photoluminescent dual mode CLC cells were further demonstrated.

CTLA4 blockade promotes vessel normalization in breast tumors via the accumulation of eosinophils.

Immune checkpoint blockade (ICB) has shown long-term survival benefits, but only in a small fraction of cancer patients. Recent studies suggest that improved vessel perfusion by ICB positively correlates with its therapeutic outcomes. However, the underlying mechanism of such a process remains unclear. Here, we show that anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) treatment-induced tumor vessel normalization was accompanied by an increased infiltration of eosinophils into breast tumors. Eosinophil accumulation was positively correlated with the responsiveness of a breast tumor to anti-CTLA4 therapy. Depletion of eosinophils subsequently negated vessel normalization, reduced antitumor immunity and attenuated tumor growth inhibition by anti-CTLA4 therapy. Moreover, intratumoral accumulation of eosinophils relied on T lymphocytes and interferon γ production. Together, these results suggest that eosinophils partially mediate the antitumor effects of CTLA4 blockade through vascular remodeling. Our findings uncover an unidentified role of eosinophils in anti-CTLA4 therapy, providing a potential new target to improve ICB therapy and to predict its efficacy.

Reversible chirality inversion of circularly polarized luminescence in a photo-invertible helical cholesteric superstructure.

A photo-invertible helical cholesteric superstructure was constructed by doping a novel chiral fluorescence photoswitch and a static dopant with opposite handedness into a nematic host. The handedness of circularly polarized luminescence can be reversibly inverted accompanied by a positive-negative change of luminescence dissymmetry factor values upon alternate light irradiations.

1,2-Dithienyldicyanoethene-Based, Visible-Light-Driven, Chiral Fluorescent Molecular Switch: Rewritable Multimodal Photonic Devices.

Reported here is the first example of a 1,2-dithienyldicyanoethene-based visible-light-driven chiral fluorescent molecular switch that exhibits reversible trans to cis photoisomerization. The trans form in solution almost completely transforms into the cis form, accompanied by a 10-fold decrease in its fluorescence intensity within 60 seconds when exposed to green light (520 nm). The reverse isomerization proceeds upon irradiation with blue light (405 nm). When doped into commercially available achiral liquid crystal hosts, this molecular switch efficiently induces luminescent helical superstructures, that is, a cholesteric phase. The intensity of the circularly polarized fluorescence as well as the selective reflection wavelength of the induced cholesteric phases can be reversibly tuned using visible light of two different wavelengths. Optically rewritable photonic devices using cholesteric films containing this molecular switch are described.