Luminescence properties of Sr2Ga2GeO7:Bi3+ phosphors and temperature sensing characteristics of co-doped Sm3.

As one of the fundamental physical quantities, temperature is extremely important in various fields. In order to study the temperature sensing characteristics of dual-emitting center phosphors, Bi3+-doped and Bi3+/Sm3+-doped Sr2Ga2GeO7 phosphors were synthesized by high-temperature solid-phase method. Under 312 nm excitation, the Sr2Ga2GeO7:Bi3+ phosphor exhibits a blue broadband emission corresponding to the 3P1 → 1S0 transition of Bi3+ ions. By testing the temperature change spectrum of phosphors, it was found that Bi3+ exhibited strong thermal sensitivity. However, due to the fact that single ion doped phosphors are easily affected by other factors when applied to the field of temperature sensing, based on the thermal sensitivity of Bi3+, Sm3+ with low temperature sensitivity was selected as the co-doped ion, and it was found that the two ions had different thermal quenching characteristics when the temperature change spectrum was tested. Using the temperature detection method based on the fluorescence intensity ratio (FIR) of the dual emission centers, it was found that the best absolute sensitivity Sa was 3.125% K-1 and the maximum relative sensitivity Sr was 1.275% K-1 in the range of 303-423 K. These results show that Sr2Ga2GeO7:Bi3+/Sm3+ phosphors have broad application prospects in the field of optical temperature sensing.

Achieving broadband near-infrared emission with superior anti-thermal quenching by optimizing the excited-state population of Cr3+ in Gd3ScGa4O12 garnet phosphors.

Cr3+-activated garnet phosphors with broadband near-infrared (NIR) emission have attracted considerable interest due to their high quantum efficiency (QE) and thermal stability for widespread advanced applications. Nevertheless, how to achieve energy-saving broadband NIR phosphors that possess anti-thermal quenching (anti-TQ) without compromising the high QE has yet to be fully addressed. Herein, we report on site reconstruction within the garnet lattice by strategically positioning Sc and Ga atoms into octahedral B sites with a mole ratio of 1 : 1 to produce Gd3ScGa4O12. A reduction in crystal field strength (CFS) is thus induced, leading to a redshift of Cr3+ broadband NIR emission. The inherent rigidity of the structure and the weak electron-phonon coupling (EPC) effect lay the groundwork for a thermally robust broadband NIR phosphor. The combination of bandgap engineering, finely optimizing the 4T2 excited state population, and precise control over the doping concentration contributes a high-performance broadband NIR emission (IQE = 82.75%) with unprecedented anti-TQ such that the NIR emission of Cr3+ even increases to 198% of its room-temperature intensity at 543 K. A prototype broadband NIR pc-LED is encapsulated to deliver an NIR output power of 125.20 mW@900 mA and a wall-plug efficiency (WPE) of 6.88%@30 mA, enabling night vision, noninvasive imaging, and non-destructive detection applications.

Integrated network pharmacology and molecular docking to investigate the potential mechanism of Tufuling on Alzheimer's disease.

Objective: This study aimed to investigate the mechanism of Tu Fu Ling in treating Alzheimer's disease (AD) using network pharmacology and molecular docking. Methods: The TCMSP and Swiss target prediction databases were utilized to confirm the active components of Tu Fu Ling and their corresponding targets, with target gene names converted using the UniProt database. Genes related to AD were collected from DisGeNET, GeneCards, and the Open Target Platform databases. Common target genes between the disease and the drug were obtained using Venny 2.1 tools and visualized using Cytoscape software. Protein-protein interaction (PPI) data were further analyzed to determine correlations between common target genes, and GO and KEGG pathway enrichment analyses were performed for intersecting genes. Finally, PYmol, AutoDock Tool, Discovery Studio 2020, and PyRx software were used for preliminary computer virtual verification and visualization of active drug ingredients and target proteins. Results: Nine active ingredients meeting the screening criteria yielded a total of 168 genes after removing duplicates. A total of 3833 target genes were collected, with 129 overlapping target genes identified. GO enrichment analysis identified 643 biological processes, 82 cellular components, and 147 molecular functions. KEGG pathway enrichment analysis also revealed a pathway closely related to AD (hsa05010: Alzheimer's disease). In molecular docking analysis, the binding affinity between the 9 active ingredients and 10 core targets ranged from -3.5 to -12.3 kcal/mol, indicating strong binding. Conclusion: This study preliminarily verified the combination of Tu Fu Ling's screened active ingredient and the calculated core target, suggesting a potential mechanism of action to improve the symptoms of AD patients through multi-target and multi-pathway approaches. This provides a valuable reference for further exploration of the pharmacological mechanism of AD and the formulation of drug therapy.

Bioinspired integrated triboelectric electronic tongue.

An electronic tongue (E-tongue) comprises a series of sensors that simulate human perception of taste and embedded artificial intelligence (AI) for data analysis and recognition. Traditional E-tongues based on electrochemical methods suffer from a bulky size and require larger sample volumes and extra power sources, limiting their applications in in vivo medical diagnosis and analytical chemistry. Inspired by the mechanics of the human tongue, triboelectric components have been incorporated into E-tongue platforms to overcome these limitations. In this study, an integrated multichannel triboelectric bioinspired E-tongue (TBIET) device was developed on a single glass slide chip to improve the device's taste classification accuracy by utilizing numerous sensory signals. The detection capability of the TBIET was further validated using various test samples, including representative human body, environmental, and beverage samples. The TBIET achieved a remarkably high classification accuracy. For instance, chemical solutions showed 100% identification accuracy, environmental samples reached 98.3% accuracy, and four typical teas demonstrated 97.0% accuracy. Additionally, the classification accuracy of NaCl solutions with five different concentrations reached 96.9%. The innovative TBIET exhibits a remarkable capacity to detect and analyze droplets with ultrahigh sensitivity to their electrical properties. Moreover, it offers a high degree of reliability in accurately detecting and analyzing various liquid samples within a short timeframe. The development of a self-powered portable triboelectric E-tongue prototype is a notable advancement in the field and is one that can greatly enhance the feasibility of rapid on-site detection of liquid samples in various settings.

Unlocking Cr3+-Cr3+ Coupling in Spinel: Ultrabroadband Near-Infrared Emission beyond 900 nm with High Efficiency and Thermal Stability.

Broadband near-infrared (NIR) phosphor-converted light-emitting diodes (pc-LEDs) hold promising potential as next-generation compact, portable, and intelligent NIR light sources. Nonetheless, the lack of high-performance broadband NIR phosphors with an emission peak beyond 900 nm has severely hindered the development and widespread application of NIR pc-LEDs. This study presents a strategy for precise control of energy-state coupling in spinel solid solutions composed of MgxZn1-xGa2O4 to tune the NIR emissions of Cr3+ activators. By combining crystal field engineering and heavy doping, the Cr3+-Cr3+ ion pair emission from the 4T2 state is unlocked, giving rise to unusual broadband NIR emission spanning 650 and 1400 nm with an emission maximum of 913 nm and a full width at half-maximum (fwhm) of 213 nm. Under an optimal Mg/Zn ratio of 4:1, the sample achieves record-breaking performance, including high internal and external quantum efficiency (IQE = 83.9% and EQE = 35.7%) and excellent thermal stability (I423 K/I298 K = 75.8%). Encapsulating the as-obtained phosphors into prototype pc-LEDs yields an overwhelming NIR output power of 124.2 mW at a driving current of 840 mA and a photoelectric conversion efficiency (PCE) of 10.5% at 30 mA, rendering high performance in NIR imaging applications.

Immune checkpoint blockade resistance in lung cancer: emerging mechanisms and therapeutic opportunities.

Immune checkpoint blockade (ICB) therapy works by inhibiting suppressive checkpoints that become upregulated after T cell activation, like PD-1/PD-L1 and CTLA-4. While the initial FDA approvals of ICB have revolutionized cancer therapies and fueled a burgeoning immuno-oncology field, more recent clinical development of new agents has been slow. Here, focusing on lung cancer, we review the latest research uncovering tumor cell intrinsic and extrinsic ICB resistance mechanisms as major hurdles to treatment efficacy and clinical progress. These include genomic and non-genomic tumor cell alterations, along with host and microenvironmental factors like the microbiome, metabolite accumulation, and hypoxia. Together, these factors can cooperate to promote immunosuppression and ICB resistance. Opportunities to prevent resistance are constantly evolving in this rapidly expanding field, with the goal of moving toward personalized immunotherapeutic regimens.

Luminescence of Sm3+ in double perovskite-type Ba2SrWO6 for insect trapping.

The predominant method for pest control has been the use of pesticides, which have been shown to have detrimental effects on soil, freshwater, and crop quality. Therefore, the development of novel and sustainable crop protection strategies has become increasingly imperative. In this study, a novel orange-red emitting Ba2SrWO6: Sm3+ phosphor was synthesized using the high-temperature solid-state reaction. Under ultraviolet excitation, the phosphors showed obvious emission peaks at 575, 614, and 662 nm. The Ba2SrWO6: Sm3+ was used to fabricate a fluorescence film with polydimethylsiloxane (PDMS), and attracted twice as many insects as the blank control group under 365 nm ultraviolet light. This material holds great potential as a fluorescent agent for insect trapping in the pest control fields of tea, cotton, eggplant, rice, potato, grape, and other agricultural industries. Our findings provide an eco-friendly approach to pest management for the increment of food production.

Smart windows based on ultraviolet-B persistent luminescence phosphors for bacterial inhibition and food preservation.

Herein, ultraviolet B (UVB) persistent luminescence phosphors containing SrAl12O19: Ce3+, Sc3+ nanoparticles were reported. Thermoluminescence (TL) spectrum analysis reveals that the shallow trap induced by Sc3+ co-doping plays an important role in photoluminescence persistent luminescence (PersL) development, while the deep trap dominates the generation of optical stimulated luminescence (OSL). Owing the appearance of deep trap, the OSL is observed under light (700 nm - 900 nm) excitation. UVB luminescence exerts good bactericidal effects on pathogenic bacteria involved in the process of food spoilage. Thus, the smart window with SrAl12O19: Ce3+, Sc3+/PDMS produces UVB PersL to efficiently inactivate Escherichia coli and Staphylococcus aureus. In addition, the presence of the smart window delays the critical point of pork decay, and greatly reduces the time of pork spoilage. It maximizes the convenience of eradicating bacteria and preserving food, thus offering a fresh perspective on the use of UV light for food sterilization and preservation.

A review of gluten detoxification in wheat for food applications: approaches, mechanisms, and implications.

With the improved knowledge of gluten-related disorders, especially celiac disease (CD), the market of gluten-free food is growing. However, the current gluten-free diet still presents challenges in terms of nutrition, acceptability, and cost due to the absence of gluten. It is important to note that gluten-related allergies or sensitivities have different underlying causes. And individuals with mild non-celiac gluten disorder symptoms may not necessarily require the same gluten-free treatments. Scientists are actively seeking alternative solutions for these consumers. This review delves into the various strategies employed by researchers for detoxifying gluten or modifying its main protein, gliadin, including genetic treatment, transamidation and deamidation, hydrolysis, and microbial treatments. The mechanisms, constraints of these techniques, their current utilization in food items, as well as their implications for gluten-related disorders, are discussed in detail. Although there is still a gap in the application of these methods as alternative solutions in the real market, the summary provided by our review could be beneficial for peers in enriching their basic ideas and developing more applicable solutions for wheat gluten detoxification.

Boosting broadband short-wave infrared emission to achieve near-unity quantum efficiency via bridging Cr3+-Ni2+ in spinel solid-solutions towards light-emitting diode applications.

Recently, short-wave infrared (SWIR) phosphor-converted light-emitting diodes (pc-LEDs) have garnered increased attention due to their widespread applications in night vision, biological imaging, and non-destructive testing. Nevertheless, the currently used SWIR phosphors suffer from poor thermal stability and low quantum efficiency. In this study, a finely tuned spinel-based solid solution, Mg0.5Zn0.5Ga2O4, is prepared to host Ni2+ to induce SWIR emission. Cr3+ is codoped as a sensitizer to bridge Cr3+ and Ni2+ ions, significantly enhancing blue light absorption and facilitating energy transfer (ET) to Ni2+ ions. The champion SWIR phosphor exhibits a broadband emission centered at 1304 nm with a full width at half maximum (FWHM) of 250 nm, achieving a near-unity internal quantum efficiency (IQE = 97.7%) and a good thermal stability (70.7%@423 K). The fabricated SWIR pc-LED device delivers a high SWIR output power of 39.9 mW at 360 mA, enabling its application in non-destructive imaging and testing.

Assessment of Heart Rate Monitoring During Exercise With Smart Wristbands and a Heart Rhythm Patch: Validation and Comparison Study.

BACKGROUND: The integration of wearable devices into fitness routines, particularly in military settings, necessitates a rigorous assessment of their accuracy. This study evaluates the precision of heart rate measurements by locally manufactured wristbands, increasingly used in military academies, to inform future device selection for military training activities. OBJECTIVE: This research aims to assess the reliability of heart rate monitoring in chest straps versus wearable wristbands. METHODS: Data on heart rate and acceleration were collected using the Q-Band Q-69 smart wristband (Mobile Action Technology Inc) and compared against the Zephyr Bioharness standard measuring device. The Lin concordance correlation coefficient, Pearson product moment correlation coefficient, and intraclass correlation coefficient were used for reliability analysis. RESULTS: Participants from a Northern Taiwanese medical school were enrolled (January 1-June 31, 2021). The Q-Band Q-69 demonstrated that the mean absolute percentage error (MAPE) of women was observed to be 13.35 (SD 13.47). Comparatively, men exhibited a lower MAPE of 8.54 (SD 10.49). The walking state MAPE was 7.79 for women and 10.65 for men. The wristband's accuracy generally remained below 10% MAPE in other activities. Pearson product moment correlation coefficient analysis indicated gender-based performance differences, with overall coefficients of 0.625 for women and 0.808 for men, varying across walking, running, and cooldown phases. CONCLUSIONS: This study highlights significant gender and activity-dependent variations in the accuracy of the MobileAction Q-Band Q-69 smart wristband. Reduced accuracy was notably observed during running. Occasional extreme errors point to the necessity of caution in relying on such devices for exercise monitoring. The findings emphasize the limitations and potential inaccuracies of wearable technology, especially in high-intensity physical activities.

Detoxification of Wheat Gluten by Enzymatic Transamidation under Reducing Condition and Its Application in Typical Food Model.

SCOPE: Gluten, the primary network builder of wheat dough, is responsible for celiac disease or wheat allergy. Transamidation of gluten under reduction conditions has been shown to reduce the potential toxicity of celiac disease, but its application in food preparation has not been extensively studied. This work investigates the use of transamidation in food preparation to address this gap in knowledge. METHODS AND RESULTS: This study investigates the effects of transamidation on the toxicity of commercial wheat flour and the apparent structure, digestive level, and rheological characteristics of resultant dough and steamed bread, as a typical food model. The results show that transamidation starts at the kneading stage, as evaluated by using R5 enzyme-linked immunoassay and rat basophils. The potential toxicity of celiac disease is reduced by about 83% when 1% microbial transglutaminase (mTG), 2% l-lysine, and 1% reduced glutathione (GSH) are added, while retaining the original physical and rheological properties of wheat flour. The additional of reduced GSH also improves the in vitro protein digestibility. CONCLUSIONS: Although it cannot be a celiac disease treatment directly, this study suggests that transamidation can serve as an alternative method for reducing the gluten toxicity of wheat flour-based food products.

Autotaxin suppresses cytotoxic T cells via LPAR5 to promote anti-PD-1 resistance in non-small cell lung cancer.

Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and effector tumor-infiltrating CD8+ T cells. Pharmacological inhibition of ATX, or the downstream receptor LPAR5, in combination with anti-PD-1 was sufficient to restore the antitumor immune response and efficaciously control lung tumor growth in multiple KP tumor models. Additionally, ATX was significantly correlated with inflammatory gene signatures, including a CD8+ cytolytic score in multiple lung adenocarcinoma patient data sets, suggesting that an activated tumor-immune microenvironment upregulates ATX and thus provides an opportunity for cotargeting to prevent acquired resistance to anti-PD-1 treatment. These data reveal the ATX/LPA axis as an immunosuppressive pathway that diminishes the immune checkpoint blockade response in lung cancer.

Sex differences in risk factors for metabolic syndrome in middle-aged and senior hospital employees: a population-based cohort study.

BACKGROUND: Several cross-sectional studies have reported risk factors for metabolic syndrome (MetS). However, these studies did not focus on sex differences in middle-aged and senior populations or employ a longitudinal design. These study design differences are important, as there are sex differences in lifestyle habits associated with MetS, and middle-aged and senior individuals have increased MetS susceptibility. Therefore, the purpose of this study was to examine whether sex differences influenced MetS risk over a ten-year follow-up period among middle-aged and senior hospital employees. METHODS: This population-based and prospective cohort study enrolled 565 participants who did not have MetS in 2012 for a ten-year repeated-measurement analysis. Data were retrieved from the hospital's Health Management Information System. Analyses included Student's t tests, χ2 tests and Cox regression. P < 0.05 indicated statistical significance. RESULTS: Male middle-aged and senior hospital employees had an elevated MetS risk (hazard ratio (HR) = 1.936, p < 0.001). Men with more than four family history risk factors had an increased risk of MetS (HR = 1.969, p = 0.010). Women who worked shift duty (HR = 1.326, p = 0.020), had more than two chronic diseases (HR = 1.513, p = 0.012), had three family history risk factors (HR = 1.623, p = 0.010), or chewed betel nuts (HR = 9.710, p = 0.002) had an increased risk of MetS. CONCLUSIONS: The longitudinal design of our study improves the understanding of sex differences in MetS risk factors in middle-aged and senior adults. A significantly elevated risk of MetS over the ten-year follow-up period was associated with male sex, shift work, the number of chronic diseases, the number of family history risk factors, and betel nut chewing. Women who chewed betel nuts had an especially increased risk of MetS. Our study indicates that population-specific studies are important for the identification of subgroups susceptible to MetS and for the implementation of hospital-based strategies.

Near-Infrared Long Afterglow in Fe3+-Activated Mg2SnO4 for Self-Sustainable Night Vision.

The advent of near-infrared (NIR) afterglow in Cr3+-doped materials has stimulated considerable interest in technological applications owing to the sustainable emission of light with good penetrability. However, the development of Cr3+-free NIR afterglow phosphors with high efficiency, low cost, and precise spectral tunability is still an open question. Herein, we report a novel Fe3+-activated NIR long afterglow phosphor composed of Mg2SnO4 (MSO), in which Fe3+ ions occupy the tetrahedral [Mg-O4] and octahedral [Sn/Mg-O6] sites, giving rise to a broadband NIR emission spanning 720-789 nm. On account of energy-level alignment, the electrons released from the traps show a preferential return to the excited energy level of Fe3+ in tetrahedral sites through tunneling, leading to a single-peak NIR afterglow centered at 789 nm with a full-width at half-maximum (fwhm) of 140 nm. The high-efficiency NIR afterglow, showing a record persistent time lasting over 31 h among Fe3+-based phosphors, is demonstrated as a self-sustainable light source for night vision applications. This work not only provides a novel Fe3+-doped high-efficiency NIR afterglow phosphor for technological applications but also establishes practical guidance for rational tuning of afterglow emissions.

Harsh Environmental-Tolerant and High-Performance Triboelectric Nanogenerator Based on Nanofiber/Microsphere Hybrid Membranes.

Triboelectric nanogenerator (TENG) can convert tiny mechanical energy into precious electrical energy. Constant improvements to the output performance of TENG is not only the driving force for its sustainable development, but also the key to expand its practical applicability in modern smart devices. However, most previous studies were conducted at room temperature, ignoring the influence of temperature on the output performance of TENG. Additionally, due to thermionic emission effect, the electrons transferred to a dielectric surface can be released into a vacuum after contact electrification. Therefore, TENG cannot maintain an effective electrical output under high-temperature conditions. Here, a series of high-temperature operatable flexible TENGs (HO-TENGs) based on nanofiber/microsphere hybrid membranes (FSHMs) was fabricated by electrospinning and electrospraying. The Voc of HO-TENG is 212 V, which is 2.33 times higher than that of control TENG. After 10,000 cycle stability tests, the HO-TENG shows excellent durability. Especially, this HO-TENG can maintain 77% electrical output at 70 °C compared to room temperature, showing excellent high-temperature operability. This study can not only provide a reference for the construction of advanced high-performance TENG, but also provide a certain experimental basis for efficient collection of mechanical energy in high-temperature environment and promote the application of TENG devices in harsh environments.

Effect of the Nintendo Ring Fit Adventure Exergame on Running Completion Time and Psychological Factors Among University Students Engaging in Distance Learning During the COVID-19 Pandemic: Randomized Controlled Trial.

BACKGROUND: The COVID-19 outbreak has not only changed the lifestyles of people globally but has also resulted in other challenges, such as the requirement of self-isolation and distance learning. Moreover, people are unable to venture out to exercise, leading to reduced movement, and therefore, the demand for exercise at home has increased. OBJECTIVE: We intended to investigate the relationships between a Nintendo Ring Fit Adventure (RFA) intervention and improvements in running time, cardiac force index (CFI), sleep quality (Chinese version of the Pittsburgh Sleep Quality Index score), and mood disorders (5-item Brief Symptom Rating Scale score). METHODS: This was a randomized prospective study and included 80 students who were required to complete a 1600-meter outdoor run before and after the intervention, the completion times of which were recorded in seconds. They were also required to fill out a lifestyle questionnaire. During the study, 40 participants (16 males and 24 females, with an average age of 23.75 years) were assigned to the RFA group and were required to exercise for 30 minutes 3 times per week (in the adventure mode) over 4 weeks. The exercise intensity was set according to the instructions given by the virtual coach during the first game. The remaining 40 participants (30 males and 10 females, with an average age of 22.65 years) were assigned to the control group and maintained their regular habits during the study period. RESULTS: The study was completed by 80 participants aged 20 to 36 years (mean 23.20, SD 2.96 years). The results showed that the running time in the RFA group was significantly reduced. After 4 weeks of physical training, it took females in the RFA group 19.79 seconds (P=.03) and males 22.56 seconds (P=.03) less than the baseline to complete the 1600-meter run. In contrast, there were no significant differences in the performance of the control group in the run before and after the fourth week of intervention. In terms of mood disorders, the average score of the RFA group increased from 1.81 to 3.31 for males (difference=1.50, P=.04) and from 3.17 to 4.54 for females (difference=1.38, P=.06). In addition, no significant differences between the RFA and control groups were observed for the CFI peak acceleration (CFIPA)_walk, CFIPA_run, or sleep quality. CONCLUSIONS: RFA could either maintain or improve an individual's physical fitness, thereby providing a good solution for people involved in distance learning or those who have not exercised for an extended period. TRIAL REGISTRATION: ClinicalTrials.gov NCT05227040; https://clinicaltrials.gov/ct2/show/NCT05227040.

Ni2+-Doped Garnet Solid-Solution Phosphor-Converted Broadband Shortwave Infrared Light-Emitting Diodes toward Spectroscopy Application.

Broadband shortwave infrared (SWIR) light-emitting diodes (LEDs), capable of advancing the next-generation solid-state smart invisible lighting technology, have sparked tremendous interest and will launch ground-breaking spectroscopy and instrumental applications. Nevertheless, the device performance is still suppressed by the low quantum efficiency and limited emission bandwidth of the critical phosphor layer. Herein, we report a high-performance Ni2+-doped garnet solid-solution broadband SWIR emitter centered at ∼1450 nm with a large full-width at half-maximum of ∼300 nm, thereby fabricating, for the first time, a directly excited Ni2+-doped garnet solid-solution phosphor-converted broadband SWIR LED device. A synergetic enhancement strategy, adding a fluxing agent and a charge compensator simultaneously, is proposed to deliver a more than 20-fold increase of the SWIR emission intensity and nearly 2-fold improvement of the thermal quenching behavior. The site occupation and mechanism behind the synergetic enhancement strategy are elucidated by a combination of experimental study and theoretical calculation. A prototype of the SWIR LED with a radiation flux of 1.25 mW is fabricated and utilized as an invisible SWIR light source to demonstrate the SWIR spectroscopy applications. This work not only opens a window to explore novel broadband SWIR phosphors but also provides a synergetic strategy to remarkably improve the performance of artificial SWIR LED light sources.

Targeted Covalent Inhibition of Small CTD Phosphatase 1 to Promote the Degradation of the REST Transcription Factor in Human Cells.

The repressor element-1 silencing transcription factor (REST) represses neuronal gene expression, whose dysregulation is implicated in brain tumors and neurological diseases. A high level of REST protein drives the tumor growth in some glioblastoma cells. While transcription factors like REST are challenging targets for small-molecule inhibitors, the inactivation of a regulatory protein, small CTD phosphatase 1 (SCP1), promotes REST degradation and reduces transcriptional activity. This study rationally designed a series of α,ß-unsaturated sulfones to serve as potent and selective covalent inhibitors against SCP1. The compounds inactivate SCP1 via covalent modification of Cys181 located at the active site entrance. Cellular studies showed that the inhibitors inactivate SCP1 in a time- and dose-dependent manner with an EC50 ∼1.5 µM, reducing REST protein levels and activating specific REST-suppressed genes. These compounds represent a promising line of small-molecule inhibitors as a novel lead for glioblastoma whose growth is driven by REST transcription activity.

Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation.

The mechanistic understanding of nascent RNAs in transcriptional control remains limited. Here, by a high sensitivity method methylation-inscribed nascent transcripts sequencing (MINT-seq), we characterized the landscapes of N6-methyladenosine (m6A) on nascent RNAs. We uncover heavy but selective m6A deposition on nascent RNAs produced by transcription regulatory elements, including promoter upstream antisense RNAs and enhancer RNAs (eRNAs), which positively correlates with their length, inclusion of m6A motif, and RNA abundances. m6A-eRNAs mark highly active enhancers, where they recruit nuclear m6A reader YTHDC1 to phase separate into liquid-like condensates, in a manner dependent on its C terminus intrinsically disordered region and arginine residues. The m6A-eRNA/YTHDC1 condensate co-mixes with and facilitates the formation of BRD4 coactivator condensate. Consequently, YTHDC1 depletion diminished BRD4 condensate and its recruitment to enhancers, resulting in inhibited enhancer and gene activation. We propose that chemical modifications of eRNAs together with reader proteins play broad roles in enhancer activation and gene transcriptional control.