Efficient Chemical Synthesis of Multi-Monoubiquitylated and Diubiquitylated Histones by the α-Halogen Ketone-Mediated Strategy.

The chemical synthesis of homogeneously ubiquitylated histones is a powerful approach to decipher histone ubiquitylation-dependent epigenetic regulation. Among the various methods, α-halogen ketone-mediated conjugation chemistry has recently been an attractive strategy to generate single-monoubiquitylated histones for biochemical and structural studies. Herein, we report the use of this strategy to prepare not only dual- and even triple-monoubiquitylated histones but also diubiquitin-modified histones. We were surprised to find that the synthetic efficiencies of multi-monoubiquitylated histones were comparable to those of single-monoubiquitylated ones, suggesting that this strategy is highly tolerant to the number of ubiquitin monomers installed onto histones. The facile generation of a series of single-, dual-, and triple-monoubiquitylated H3 proteins enabled us to evaluate the influence of ubiquitylation patterns on the binding of DNA methyltransferase 1 (DNMT1) to nucleosomes. Our study highlights the potential of site-specific conjugation chemistry to generate chemically defined histones for epigenetic studies.

Terminal halogen-containing rod-like liquid crystals: Synthesis, self-assembly, photophysical and mechanochromism properties.

Five series of cyanostilbene-based rod-like liquid crystals containing one different terminal atom (H, F, Cl, Br and I) at one end and one terminal aliphatic chain with different numbers of carbon atoms at the other end were reported by Suzuki coupling and Knoevenagel reactions. The influence of terminal halogen atoms and terminal chain length on the self-assembly, AIE behavior, temperature-dependent emission and mechanochromism behavior was explored by POM, DSC, XRD, SEM, absorption spectra and emission spectra. All the compounds are enantiotropic liquid crystals. The lowest non-halogen substituted homologue exhibited solo N phase, but the higher non-halogen substituted homologues exhibited mesogenic transition from SmA phase to N phase upon rising temperature. All the lowest halogen substituted homologues exhibited mesogenic transition from SmA phase to N phase upon rising temperature and all the higher homologues only exhibited SmA. The distinct mesogenic phase transition could be attributed to the intermolecular interaction produced by terminal halogen and the rigidity of the terminal aliphatic chain. All the non-halogen substituted compounds and halogen substituted compounds with smaller terminal halogen atom (F, Cl and Br atom) exhibited AIE behaviors, whereas the iodinated compounds exhibited extremely weak emission in solution and aggregated states due to the heavy atoms effect. These compounds also exhibited distinct solid-state emission with blue or cyan fluorescence, which could be quenched by increasing temperature. The reversible mechanochromism behavior was also achieved in all the compounds. The mechanical force induced quench in emission in non-halogen substituted compounds and halogen substituted compounds with smaller terminal halogen atom (F, Cl and Br atom), whereas enhancement in iodinated compounds. The reversible mechanochromism behavior endowed these compounds with potential applications in rewritable paper and anti-counterfeiting. The interesting properties in these liquid crystals would be attributed to the balance of the halogen-halogen interactions, heavy atom effect, steric-hindrance effect and chain length. These investigations would be helpful to understand the relationship between chemical structures and properties.

Non-linear responses via agglomeration and aggregation of gold nanoparticles for surface-enhanced Raman spectroscopy (SERS) coupled with chemometric analysis for chlorpyrifos detection.

This study investigates the behaviour of gold nanoparticles (AuNPs) when exposed to chlorpyrifos, an agricultural pesticide, and its application in detecting the pesticide via surface-enhanced Raman spectroscopy (SERS). Under synergistic addition of NaCl, AuNPs undergo agglomeration at lower chlorpyrifos concentrations but aggregation at higher concentrations, resulting in a distinctive nonlinear SERS response. A linear relationship is obtained between 0.001 and 1 ppm with detection limit (LOD) of 0.009 ppm, while an inverse response is observed at higher concentrations (1-1000 ppm) with a LOD of 1 ppm. Combining the colorimetric response of AuNP solutions, their absorbance spectra, and principal component analysis can improve detection reliability. The assay, coupled with a simple recovery method using acetonitrile swabbing, achieves high reproducibility in detecting chlorpyrifos in cucumber, even at concentrations as low as 0.11 ppm. This approach can be tailored for various chlorpyrifos concentrations not only in cucumbers but also in different food matrices.

In-Doped ZnO Electron Transport Layer for High-Efficiency Ultrathin Flexible Organic Solar Cells.

Sol-gel processed zinc oxide (ZnO) is one of the most widely used electron transport layers (ETLs) in inverted organic solar cells (OSCs). The high annealing temperature (≈200 °C) required for sintering to ensure a high electron mobility however results in severe damage to flexible substrates. Thus, flexible organic solar cells based on sol-gel processed ZnO exhibit significantly lower efficiency than rigid devices. In this paper, an indium-doping approach is developed to improve the optoelectronic properties of ZnO layers and reduce the required annealing temperature. Inverted OSCs based on In-doped ZnO (IZO) exhibit a higher efficiency than those based on ZnO for a range of different active layer systems. For the PM6:L8-BO system, the efficiency increases from 17.0% for the pristine ZnO-based device to 17.8% for the IZO-based device. The IZO-based device with an active layer of PM6:L8-BO:BTP-eC9 exhibits an even higher efficiency of up to 18.1%. In addition, a 1.2-micrometer-thick inverted ultrathin flexible organic solar cell is fabricated based on the IZO ETL that achieves an efficiency of 17.0% with a power-per-weight ratio of 40.4 W g-1, which is one of the highest efficiency for ultrathin (less than 10 micrometers) flexible organic solar cells.

Coloration in Equine: Overview of Candidate Genes Associated with Coat Color Phenotypes.

Variation in coat color among equids has attracted significant interest in genetics and breeding research. The range of colors is primarily determined by the type, concentration, and distribution of melanin pigments, with the balance between eumelanin and pheomelanin influenced by numerous genetic factors. Advances in genomic and sequencing technologies have enabled the identification of several candidate genes that influence coat color, thereby clarifying the genetic basis of these diverse phenotypes. In this review, we concisely categorize coat coloration in horses and donkeys, focusing on the biosynthesis and types of melanin involved in pigmentation. Moreover, we highlight the regulatory roles of some key candidate genes, such as MC1R, TYR, MITF, ASIP, and KIT, in coat color variation. Moreover, the review explores how coat color relates to selective breeding and specific equine diseases, offering valuable insights for developing breeding strategies that enhance both the esthetic and health aspects of equine species.

Regulatory Role of Meox1 in Muscle Growth of Sebastes schlegelii.

Meox1 is a critical transcription factor that plays a pivotal role in embryogenesis and muscle development. It has been established as a marker gene for growth-specific muscle stem cells in zebrafish. In this study, we identified the SsMeox1 gene in a large teleost fish, Sebastes schlegelii. Through in situ hybridization and histological analysis, we discovered that SsMeox1 can be employed as a specific marker of growth-specific muscle stem cells, which originate from the somite stage and are primarily situated in the external cell layer (ECL) and myosepta, with a minor population distributed among muscle fibers. The knockdown of SsMeox1 resulted in a significant increase in Ccnb1 expression, subsequently promoting cell cycle progression and potentially accelerating the depletion of the stem cell pool, which ultimately led to significant growth retardation. These findings suggest that SsMeox1 arrests the cell cycle of growth-specific muscle stem cells in the G2 phase by suppressing Ccnb1 expression, which is essential for maintaining the stability of the growth-specific muscle stem cell pool. Our study provides significant insights into the molecular mechanisms underlying the indeterminate growth of large teleosts.

Extracting the winter wheat using the decision tree based on time series dual-polarization SAR feature and NDVI.

Winter wheat is one of the most important crops in the world. It is great significance to obtain the planting area of winter wheat timely and accurately for formulating agricultural policies. Due to the limited resolution of single SAR data and the susceptibility of single optical data to weather conditions, it is difficult to accurately obtain the planting area of winter wheat using only SAR or optical data. To solve the problem of low accuracy of winter wheat extraction only using optical or SAR images, a decision tree classification method combining time series SAR backscattering feature and NDVI (Normalized Difference Vegetation Index) was constructed in this paper. By synergy using of SAR and optical data can compensate for their respective shortcomings. First, winter wheat was distinguished from other vegetation by NDVI at the maturity stage, and then it was extracted by SAR backscattering feature. This approach facilitates the semi-automated extraction of winter wheat. Taking Yucheng City of Shandong Province as study area, 9 Sentinel-1 images and one Sentinel-2 image were taken as the data sources, and the spatial distribution of winter wheat in 2022 was obtained. The results indicate that the overall accuracy (OA) and kappa coefficient (Kappa) of the proposed method are 96.10% and 0.94, respectively. Compared with the supervised classification of multi-temporal composite pseudocolor image and single Sentinel-2 image using Support Vector Machine (SVM) classifier, the OA are improved by 10.69% and 5.66%, respectively. Compared with using only SAR feature for decision tree classification, the producer accuracy (PA) and user accuracy (UA) for extracting the winter wheat are improved by 3.08% and 8.25%, respectively. The method proposed in this paper is rapid and accurate, and provide a new technical method for extracting winter wheat.

Lithium Therapy's Potential to Lower Dementia Risk and the Prevalence of Alzheimer's Disease: A Meta-Analysis.

INTRODUCTION: Dementia is a neurodegenerative disease with insidious onset and progressive progression, of which the most common type is Alzheimer's disease (AD). Lithium, a trace element in the body, has neuroprotective properties. However, whether lithium can treat dementia or AD remains a highly controversial topic. Therefore, we conducted a meta-analysis. METHODS: A systematic literature review was conducted on PubMed, Embase, and Web of Science. Comparison of the effects of lithium on AD or dementia in terms of use, duration, and dosage, and meta-analysis to test whether lithium therapy is beneficial in ameliorating the onset of dementia or AD. Sensitivity analyses were performed using a stepwise exclusion method. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. We determined the relative risk (RR) between patient groups using a random-effects model. RESULTS: A total of seven studies were included. The forest plot results showed that taking lithium therapy reduced the risk of AD (RR 0.59, 95% confidence interval [CI]: 0.44-0.78) and is also protective in reducing the risk of dementia (RR 0.66, 95% CI: 0.56-0.77). The duration of lithium therapy was able to affect dementia incidence (RR 0.70, 95% CI: 0.55-0.88); however, it is unclear how this effect might manifest in AD. It is also uncertain how many prescriptions for lithium treatment lower the chance of dementia development. CONCLUSION: The duration of treatment and the usage of lithium therapy seem to lower the risk of AD and postpone the onset of dementia.

Integrated network toxicology, molecular docking, and in vivo experiments to elucidate molecular mechanism of aflatoxin B1 hepatotoxicity.

Due to the rise in temperature and sea level caused by climate change, the detection rate of aflatoxin B1 (AFB1) in food crops has increased dramatically, and the frequency and severity of aflatoxicosis in humans and animals are also increasing. AFB1 has strong hepatotoxicity, causing severe liver damage and even cancer. However, the mechanism of AFB1 hepatotoxicity remains unclear. By integrating network toxicology, molecular docking and in vivo experiments, this research was designed to explore the potential hepatotoxicity mechanisms of AFB1. Thirty-three intersection targets for AFB1-induced liver damage were identified using online databases. PI3K/AKT1, MAPK, FOXO1 signaling pathways, and apoptosis were significantly enriched. In addition, the proteins of ALB, AKT1, PIK3CG, MAPK8, HSP90AA1, PPARA, MAPK1, EGFR, FOXO1, and IGF1 exhibited good affinity with AFB1. In vivo experiments, significant pathological changes occurred in the liver of mice. AFB1 induction increased the expression levels of EGFR, ERK, and FOXO1, and decreased the expression levsls of PI3K and AKT1. Moreover, AFB1 treatment caused an increase in Caspase3 expression, and a decrease in Bcl2/Bax ratio. By combining network toxicology with in vivo experiments, this study confirms for the first time that AFB1 promotes the FOXO1 signaling pathway by inactivating PI3K/AKT1 and activating EGFR/ERK signaling pathways, hence aggravating hepatocyte apoptosis. This research provides new strategies for studying the toxicity of environmental pollutants and new possible targets for the development of hepatoprotective drugs.

Mental health conditions in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

OBJECTIVES: The reported prevalence of mental health conditions (MHCs) in people with systemic lupus erythematosus (SLE) ranges widely. Whether MHCs are associated with increased risk of SLE or the outcomes of the disease is unclear. This paper aimed to conduct an umbrella and updated meta-analysis of MHCs in people with SLE and to identify whether MHCs are associated with the risk of SLE or patient outcomes. METHODS: We comprehensively searched PubMed, Web of Science, and Embase databases to identify relevant studies published before June 2023. Random-effect models were used to calculate the pooled prevalence and risk ratios for each MHC. RESULTS: 203 studies with 1485094 individuals were included. The most MHCs observed in patients with SLE were sleep disturbance (59.7% [95% CI, 52.4%-66.8%]) among adults and cognitive dysfunction (63.4% [95% CI, 46.9%-77.9%]) among children. We found that depressive disorders (RR = 2.30, 95% CI = 1.94-2.75) and posttraumatic stress disorder (RR = 1.93, 95% CI = 1.61-2.31) in the general population were significantly associated with an increased likelihood of developing SLE. Furthermore, concurrent MHCs were linked to unfavorable outcomes in patients with SLE, such as decreased quality of life, increased risk of unemployment, and other somatic comorbidities. CONCLUSION: Our study demonstrated a high prevalence of MHCs among patients with SLE. Individuals with pre-existing mental disorders exhibited an elevated susceptibility to developing SLE, and patients presenting with MHCs were at increased risk of experiencing suboptimal health and functional outcomes. Therefore, evaluating and preventing MHCs should be considered as an integral component of the comprehensive treatment strategy for SLE.

Elucidating the Role of Transcriptomic Networks and DNA Methylation in Collagen Deposition of Dezhou Donkey Skin.

DNA methylation represents a predominant epigenetic modification with broad implications in various biological functions. Its role is particularly significant in the process of collagen deposition, a fundamental aspect of dermal development in donkeys. Despite its critical involvement, the mechanistic insights into how DNA methylation influences collagen deposition in donkey skin remain limited. In this study, we employed whole genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) to investigate the epigenetic landscape and gene expression profiles in the dorsal skin tissues of Dezhou donkeys across three developmental stages: embryonic (YD), juvenile (2-year-old, MD), and mature (8-year-old, OD). Our analysis identified numerous differentially methylated genes that play pivotal roles in skin collagen deposition and overall skin maturation, including but not limited to COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, GLUL, SFRP2, FOSL1, SERPINE1, MMP1, MMP2, MMP9, and MMP13. Notably, we observed an inverse relationship between gene expression and DNA methylation proximal to transcription start sites (TSSs), whereas a direct correlation was detected in regions close to transcription termination sites (TTSs). Detailed bisulfite sequencing analyses of the COL1A1 promoter region revealed a low methylation status during the embryonic stage, correlating with elevated transcriptional activity and gene expression levels. Collectively, our findings elucidate key genetic markers associated with collagen deposition in the skin of Dezhou donkeys, underscoring the significant regulatory role of DNA methylation. This research work contributes to the foundational knowledge necessary for the genetic improvement and selective breeding of Dezhou donkeys, aiming to enhance skin quality attributes.

H2S donor S-propargyl-cysteine for skin wound healing improvement via smart transdermal delivery.

Hydrogen sulfide for wound healing has drawn a lot of attention recently. In this research, the S-propargyl-cysteine (SPRC), an endogenous H2S donor, was loaded on carbomer hydrogel, and a copper sheet rat burn model was developed. Pathological changes in rat skin tissue were examined using hematoxylin-eosin (HE) and Masson staining. The immunohistochemistry (IHC) staining was performed to detect the expression of Collagen I (Col I) and Collagen III (Col III). The mRNA levels of interleukin (IL)-6, Col Iα2, Col IIIα1, tissue inhibitors of metalloproteinase (TIMP)-1, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-ß1 were examined by quantitative real-time chain polymerase reaction. The findings demonstrated that the collagen layer was thicker in the SPRC group during the proliferative phase, SPRC hydrogel promoted VEGF expression. In the late stage of wound healing, the expression of IL-6, TIMP-1, MMP-9, and TGF-ß1 was inhibited, and the Col I content was closer to that of normal tissue. These results surface that SPRC hydrogel can promote wound healing and play a positive role in reducing scar formation. Our results imply that SPRC can facilitate wound healing and play a positive role in reducing scar formation.

Decomposition of dynamic transcriptomic responses during effector-triggered immunity reveals conserved responses in two distinct plant cell populations.

Rapid plant immune responses in the appropriate cells are needed for effective defense against pathogens. Although transcriptome analysis is often used to describe overall immune responses, collection of transcriptome data with sufficient resolution in both space and time is challenging. We reanalyzed public Arabidopsis time-course transcriptome data obtained after low-dose inoculation with a Pseudomonas syringae strain expressing the effector AvrRpt2, which induces effector-triggered immunity in Arabidopsis. Double-peak time-course patterns are prevalent among thousands of upregulated genes. We implemented a multi-compartment modeling approach to decompose the double-peak pattern into two single-peak patterns for each gene. The decomposed peaks reveal an "echoing" pattern: the peak times of the first and second peaks correlate well across most upregulated genes. We demonstrated that the two peaks likely represent responses of two distinct cell populations that respond either cell autonomously or indirectly to AvrRpt2. Thus, the peak decomposition has extracted spatial information from the time-course data. The echoing pattern also indicates a conserved transcriptome response with different initiation times between the two cell populations despite different elicitor types. A gene set highly overlapping with the conserved gene set is also upregulated with similar kinetics during pattern-triggered immunity. Activation of a WRKY network via different entry-point WRKYs can explain the similar but not identical transcriptome responses elicited by different elicitor types. We discuss potential benefits of the properties of the WRKY activation network as an immune signaling network in light of pressure from rapidly evolving pathogens.

Advancements in Genetic Marker Exploration for Livestock Vertebral Traits with a Focus on China.

In livestock breeding, the number of vertebrae has gained significant attention due to its impact on carcass quality and quantity. Variations in vertebral traits have been observed across different animal species and breeds, with a strong correlation to growth and meat production. Furthermore, vertebral traits are classified as quantitative characteristics. Molecular marker techniques, such as marker-assisted selection (MAS), have emerged as efficient tools to identify genetic markers associated with vertebral traits. In the current review, we highlight some key potential genes and their polymorphisms that play pivotal roles in controlling vertebral traits (development, length, and number) in various livestock species, including pigs, donkeys, and sheep. Specific genetic variants within these genes have been linked to vertebral development, number, and length, offering valuable insights into the genetic mechanisms governing vertebral traits. This knowledge has significant implications for selective breeding strategies to enhance structural characteristics and meat quantity and quality in livestock, ultimately improving the efficiency and quality of the animal husbandry industry.

Carboxyl-Modified Quantum Dots for NIR-IIb Bone Marrow Imaging.

Real-time, noninvasive, and nonradiative bone imaging can directly visualize bone health but requires bone-targeted probes with high specificity. Herein, we propose that carboxyl-rich fluorescent nanoprobes are easily absorbed by macrophages in bone marrow during circulation, enabling optical bone marrow imaging in vivo. We used PbS/CdS core-shell quantum dots with NIR-IIb (1500-1700 nm) emission as substrates to prepare the carboxyl-rich nanoprobe. In vivo NIR-IIb fluorescence imaging with the nanoprobes showed high resolution and penetration depth in bone tissues and allowed for imaging-guided fracture diagnosis. Bone tissue slices showed substantial accumulation of carboxyl nanoprobes in the bone marrow and strong colocalization with macrophages. Similar results with CdSe quantum dots and an organic nanofluorophore suggest that carboxyl surface modification is effective to achieve bone marrow targeting, providing a novel strategy for developing bone/bone marrow imaging probes.

Deubiquitinating enzyme PSMD7 promotes bladder cancer development: Involvement of RAB1A stabilization.

BACKGROUND: Proteasome 26S subunit, non-ATPase 7 (PSMD7) is a deubiquitinating enzyme that is involved in the stability of ubiquitinated proteins and participates in the development of multiple types of cancer. The roles of PSMD7 and its potential mechanisms in bladder cancer (BC) remain elusive. METHODS: In this study, we identified that PSMD7 was overexpressed in BC tissues based on gene expression omnibus (GEO) database and TNMplot web. To investigate the functional role of PSMD7, two BC cell lines, T24 and 5637, were selected. The cells were transfected with vectors containing short hairpin RNAs against PSMD7 or plasmids containing full-length PSMD7 to knockdown or overexpress PSMD7. RESULTS: Our results revealed that silencing PSMD7 inhibited cell proliferation, cycle progression, migration, invasion, and promoted cell apoptosis, whereas PSMD7 overexpression led to the opposite effects in the BC cells. Mechanically, PSMD7 influenced the protein expression but not the mRNA expression of the Ras-related protein Rab-1 A (RAB1A). PSMD7 combined with RAB1A and negatively regulated its ubiquitination, indicating that PSMD7 enhanced the stability of RAB1A through post-transcriptional modification. Moreover, the rescue experiment demonstrated that RAB1A was an important downstream effector molecule of PSMD7. Besides, the negative regulation of silencing PSMD7 on tumor growth was confirmed in mice. CONCLUSIONS: Our study substantiated a novel mechanism by which PSMD7 stabilized RAB1A to accelerate the progression of BC.

Dielectric Filler-Induced Hybrid Interphase Enabling Robust Solid-State Li Metal Batteries at High Areal Capacity.

The fillers in composite solid-state electrolyte are mainly responsible for the enhancement of the conduction of Li ions but barely regulate the formation of solid electrolyte interphase (SEI). Herein, a unique filler of dielectric NaNbO3 for the poly(vinylidene fluoride) (PVDF)-based polymer electrolyte, which is subjected to the exchange of Li+ and Na+ during cycling, is reported and the substituted Na+ is engaged in the construction of a fluorinated Li/Na hybrid SEI with high Young's modulus, facilitating the fast transport of Li+ at the interface at a high areal capacity and suppressing the Li dendrite growth. The dielectric NaNbO3 also induces the generation of high-dielectric ß phase of PVDF to promote the dissociation of Li salt. The Li/Li symmetrical cell exhibits a long-term dendrite-free cycling over 600 h at a high areal capacity of 3 mA h cm-2. The LiNi0.8Mn0.1Co0.1O2/Li solid-state cells with NaNbO3 stably cycle 2200 times at 2 C and that paired with high-loading cathode (10 mg cm-2) can stably cycle for 150 times and exhibit excellent performances at -20 °C. This work provides a novel design principle of fillers undertaking interfacial engineering in composite solid-state electrolytes for developing the safe and stable solid-state lithium metal battery.

Wild-type IDH1 maintains NSCLC stemness and chemoresistance through activation of the serine biosynthetic pathway.

Tumor-initiating cells (TICs) reprogram their metabolic features to meet their bioenergetic, biosynthetic, and redox demands. Our previous study established a role for wild-type isocitrate dehydrogenase 1 (IDH1WT) as a potential diagnostic and prognostic biomarker for non-small cell lung cancer (NSCLC), but how IDH1WT modulates NSCLC progression remains elusive. Here, we report that IDH1WT activates serine biosynthesis by enhancing the expression of phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1), the first and second enzymes of de novo serine synthetic pathway. Augmented serine synthesis leads to GSH/ROS imbalance and supports pyrimidine biosynthesis, maintaining tumor initiation capacity and enhancing gemcitabine chemoresistance. Mechanistically, we identify that IDH1WT interacts with and stabilizes PHGDH and fragile X-related protein-1 (FXR1) by impeding their association with the E3 ubiquitin ligase parkin by coimmunoprecipitation assay and proximity ligation assay. Subsequently, stabilized FXR1 supports PSAT1 mRNA stability and translation, as determined by actinomycin D chase experiment and in vitro translation assay. Disrupting IDH1WT-PHGDH and IDH1WT-FXR1 interactions synergistically reduces NSCLC stemness and sensitizes NSCLC cells to gemcitabine and serine/glycine-depleted diet therapy in lung cancer xenograft models. Collectively, our findings offer insights into the role of IDH1WT in serine metabolism, highlighting IDH1WT as a potential therapeutic target for eradicating TICs and overcoming gemcitabine chemoresistance in NSCLC.

The effect of light therapy on sleep disorders and psychobehavioral symptoms in patients with Alzheimer's disease: A meta-analysis.

BACKGROUND: Although Alzheimer's disease (AD) mainly affects cognitive function, it is often accompanied by sleep disorders and psychobehavioral symptoms. These symptoms, including depression, agitation, and psychotic symptoms, are prominent hospitalization causes among patients with AD. Currently, relatively more research exists on light therapy for sleep disorders, while those on psychobehavioral symptoms are gradually increasing. However, no consensus exists on these results because of the vulnerability of light therapy to multiple factors, including light intensity and duration. Thus, further research investigating this aspect is warranted. OBJECTIVE: To evaluate the efficacy of light therapy in improving sleep disorders and psychobehavioural symptoms in patients with AD. METHODS: In this meta-analysis, relevant literature was searched in Embase, the Clinical Trials Registry, Web of Science, PubMed, and the Cochrane Library up to December 2022. Furthermore, a fixed-effects model was used for data analysis. RESULTS: Fifteen randomized controlled trials involving 598 patients with AD were included. In the case of sleep disorders, our meta-analysis revealed that light therapy significantly improved sleep efficiency (MD = -2.42, 95% CI = -3.37 to -1.48, p < 0.00001), increased interdaily stability (MD = -0.04, 95% CI = -0.05 to -0.03, p < 0.00001), and reduced intradaily variability (MD = -0.07, 95% CI = -0.10 to -0.05, p < 0.00001). With respect to psychotic behavior, light therapy was found to alleviate depression (MD = -2.55, 95% CI = -2.98 to -2.12, p < 0.00001) as well as reduce agitation (MD = -3.97, 95% CI = -5.09 to -2.84, p < 0.00001) and caregiver burden (MD = -3.57, 95% CI = -5.28 to -1.87, p < 0.00001). CONCLUSION: Light therapy leads to significant improvement in sleep and psychobehavioral symptoms and is associated with relatively fewer side effects in patients with AD, indicating its potential as a promising treatment option for AD.

ID1 expressing macrophages support cancer cell stemness and limit CD8+ T cell infiltration in colorectal cancer.

Elimination of cancer stem cells (CSCs) and reinvigoration of antitumor immunity remain unmet challenges for cancer therapy. Tumor-associated macrophages (TAMs) constitute the prominant population of immune cells in tumor tissues, contributing to the formation of CSC niches and a suppressive immune microenvironment. Here, we report that high expression of inhibitor of differentiation 1 (ID1) in TAMs correlates with poor outcome in patients with colorectal cancer (CRC). ID1 expressing macrophages maintain cancer stemness and impede CD8+ T cell infiltration. Mechanistically, ID1 interacts with STAT1 to induce its cytoplasmic distribution and inhibits STAT1-mediated SerpinB2 and CCL4 transcription, two secretory factors responsible for cancer stemness inhibition and CD8+ T cell recruitment. Reducing ID1 expression ameliorates CRC progression and enhances tumor sensitivity to immunotherapy and chemotherapy. Collectively, our study highlights the pivotal role of ID1 in controlling the protumor phenotype of TAMs and paves the way for therapeutic targeting of ID1 in CRC.