The HEAT repeat protein HPO-27 is a lysosome fission factor.

Lysosomes are degradation and signalling centres crucial for homeostasis, development and ageing1. To meet diverse cellular demands, lysosomes remodel their morphology and function through constant fusion and fission2,3. Little is known about the molecular basis of fission. Here we identify HPO-27, a conserved HEAT repeat protein, as a lysosome scission factor in Caenorhabditis elegans. Loss of HPO-27 impairs lysosome fission and leads to an excessive tubular network that ultimately collapses. HPO-27 and its human homologue MROH1 are recruited to lysosomes by RAB-7 and enriched at scission sites. Super-resolution imaging, negative-staining electron microscopy and in vitro reconstitution assays reveal that HPO-27 and MROH1 self-assemble to mediate the constriction and scission of lysosomal tubules in worms and mammalian cells, respectively, and assemble to sever supported membrane tubes in vitro. Loss of HPO-27 affects lysosomal morphology, integrity and degradation activity, which impairs animal development and longevity. Thus, HPO-27 and MROH1 act as self-assembling scission factors to maintain lysosomal homeostasis and function.

Atranorin inhibits NLRP3 inflammasome activation by targeting ASC and protects NLRP3 inflammasome-driven diseases.

Aberrant NLRP3 activation has been implicated in the pathogenesis of numerous inflammation-associated diseases. However, no small molecular inhibitor that directly targets NLRP3 inflammasome has been approved so far. In this study, we show that Atranorin (C19H18O8), the secondary metabolites of lichen family, effectively prevents NLRP3 inflammasome activation in macrophages and dendritic cells. Mechanistically, Atranorin inhibits NLRP3 activation induced cytokine secretion and cell pyroptosis through binding to ASC protein directly and therefore restraining ASC oligomerization. The pharmacological effect of Atranorin is evaluated in NLRP3 inflammasome-driven disease models. Atranorin lowers serum IL-1ß and IL-18 levels in LPS induced mice acute inflammation model. Also, Atranorin protects against MSU crystal induced mice gouty arthritis model and lowers ankle IL-1ß level. Moreover, Atranorin ameliorates intestinal inflammation and epithelial barrier dysfunction in DSS induced mice ulcerative colitis and inhibits NLRP3 inflammasome activation in colon. Altogether, our study identifies Atranorin as a novel NLRP3 inhibitor that targets ASC protein and highlights the potential therapeutic effects of Atranorin in NLRP3 inflammasome-driven diseases including acute inflammation, gouty arthritis and ulcerative colitis.

Visualizing Large Facet-Dependent Electronic Tuning in Monolayer WSe2 on Au Surfaces.

Two-dimensional transition metal dichalcogenides (TMDs) have shown great importance in the development of novel ultrathin optoelectronic devices owing to their exceptional electronic and photonic properties. Effectively tuning their electronic band structures is not only desired in electronics applications but also can facilitate more novel properties. In this work, we demonstrate that large electronic tuning on a WSe2 monolayer can be realized by different facets of a Au-foil substrate, forming in-plane p-n junctions with remarkable built-in electric fields. This facet-dependent tuning effect is directly visualized by using scanning tunneling microscopy and differential conductance (dI/dV) spectroscopy. First-principles calculations reveal that the atomic arrangement of the Au facet effectively changes the interfacial coupling and charge transfer, leading to different magnitudes of charge doping in WSe2. Our study would be beneficial for future customized fabrication of TMD-junction devices via facet-specific construction on the substrate.

STING inhibitor ameliorates LPS-induced ALI by preventing vascular endothelial cells-mediated immune cells chemotaxis and adhesion.

Acute lung injury (ALI) is a common and devastating clinical disorder featured by excessive inflammatory responses. Stimulator of interferon genes (STING) is an indispensable molecule for regulating inflammation and immune response in multiple diseases, but the role of STING in the ALI pathogenesis is not well elucidated. In this study, we explored the molecular mechanisms of STING in regulating lipopolysaccharide (LPS)-induced lung injury. Mice were pretreated with a STING inhibitor C-176 (15, 30 mg/kg, i.p.) before LPS inhalation to induce ALI. We showed that LPS inhalation significantly increased STING expression in the lung tissues, whereas C-176 pretreatment dose-dependently suppressed the expression of STING, decreased the production of inflammatory cytokines including TNF-α, IL-6, IL-12, and IL-1ß, and restrained the expression of chemokines and adhesion molecule vascular cell adhesion protein-1 (VCAM-1) in the lung tissues. Consistently, in vitro experiments conducted in TNF-α-stimulated HMEC-1cells (common and classic vascular endothelial cells) revealed that human STING inhibitor H-151 or STING siRNA downregulated the expression levels of adhesion molecule and chemokines in HMEC-1cells, accompanied by decreased adhesive ability and chemotaxis of immunocytes upon TNF-α stimulation. We further revealed that STING inhibitor H-151 or STING knockdown significantly decreased the phosphorylation of transcription factor STAT1, which subsequently influenced its binding to chemokine CCL2 and adhesive molecule VCAM-1 gene promoter. Collectively, STING inhibitor can alleviate LPS-induced ALI in mice by preventing vascular endothelial cells-mediated immune cell chemotaxis and adhesion, suggesting that STING may be a promising therapeutic target for the treatment of ALI.

Heme protects intestinal mucosal barrier in DSS-induced colitis through regulating macrophage polarization in both HO-1-dependent and HO-1-independent way.

Hemoglobin-derived heme was reported to play protective roles in hemorrhagic diseases by modulating the macrophages toward recovery. Mucosal bleeding is one of the pathological features of inflammatory bowel diseases (IBD). However, whether heme provides anti-inflammatory profiles in macrophages, thus contributing to the intestinal mucosal barrier protection, is unclear. In the current study, we investigated the beneficial effects of heme on DSS-induced colitis mice and explored the underlying mechanisms. In vivo, systemic heme supplementation by hemin injection relieved intestinal inflammation and remedied intestinal mucosal barrier damage by correcting abnormal intestinal macrophage polarization. In vitro, we confirmed the reciprocally regulating effects of hemin on M1/M2 macrophage polarization in BMDM. Intriguingly, with knockdown of HO-1, the inhibiting effects of hemin on M1 polarization were maintained, while the promoting effects on M2 polarization were reversed. Further research proved that hemin repressed the inflammatory profiles in macrophages through inhibiting the translocation of NF-κB p65 by disrupting IRF5-NF-κB p65 complex formation in Spi-C-dependent way. In conclusion, these results showed that the modification of colon tissue microenvironment with heme supplementation plays a protective role in DSS-induced colitis mice through regulating the macrophage polarization in both HO-1-dependent and HO-1-independent way, indicating a new choice to therapeutically modulate the macrophage function and prevent IBD.

Triptolide analog LLDT-8 ameliorates psoriasis-like dermatitis in BALB/c mice via suppressing the IL-36α signaling pathway.

Triptolide has shown a good immunosuppressive effect on autoimmune diseases. However, the toxicity limited its widely clinical practice. In this study, we investigated the effects and underlying mechanisms of (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, on a murine psoriasis-like dermatitis model and related cell lines. Here, we showed that LLDT-8 significantly attenuated symptoms of psoriasis-like dermatitis induced by imiquimod (IMQ, a TLR7 agonist) by reducing the psoriasis area and severity index (PASI) score and inflammatory parameters. The action of LLDT-8 was involved in down-regulated interleukin (IL)-36α expression and blocked IL-36α pathway by LC-MS-based label-free quantitative (LFQ) proteomic approach and further experiments. Meanwhile, we observed that LLDT-8 significantly inhibited the expression of IL-36α in R837-treated bone marrow-derived dendritic cells (BMDCs). In conclusion, LLDT-8 notably alleviated IMQ-induced psoriasis-like skin inflammation via suppressing the IL-36α signaling pathway, suggesting LLDT-8 might be a potential drug for the treatment of psoriasis.

Directing Group Enables Electrochemical Selectively Meta-Bromination of Pyridines under Mild Conditions.

Without the use of catalysts and oxidants, a facile and sustainable electrochemical bromination protocol was developed. By introducing the directing groups, the regioselectivity of pyridine derivatives could be controlled at the meta-position utilizing the inexpensive and safe bromine salts at room temperature. A variety of brominated pyridine derivatives were obtained in 28-95% yields, and the reaction could be readily performed at a gram scale. By combining the installation and removing the directing group, the concept of meta-bromination of pyridines could be verified.

Semi-Synthesis, Cytotoxic Evaluation, and Structure-Activity Relationships of Brefeldin A Derivatives with Antileukemia Activity.

Brefeldin A (1), a potent cytotoxic natural macrolactone, was produced by the marine fungus Penicillium sp. (HS-N-29) from the medicinal mangrove Acanthus ilicifolius. Series of its ester derivatives 2-16 were designed and semi-synthesized, and their structures were characterized by spectroscopic methods. Their cytotoxic activities were evaluated against human chronic myelogenous leukemia K562 cell line in vitro, and the preliminary structure-activity relationships revealed that the hydroxy group played an important role. Moreover, the monoester derivatives exhibited stronger cytotoxic activity than the diester derivatives. Among them, brefeldin A 7-O-2-chloro-4,5-difluorobenzoate (7) exhibited the strongest inhibitory effect on the proliferation of K562 cells with an IC50 value of 0.84 µM. Further evaluations indicated that 7 induced cell cycle arrest, stimulated cell apoptosis, inhibited phosphorylation of BCR-ABL, and thereby inactivated its downstream AKT signaling pathway. The expression of downstream signaling molecules in the AKT pathway, including mTOR and p70S6K, was also attenuated after 7-treatment in a dose-dependent manner. Furthermore, molecular modeling of 7 docked into 1 binding site of an ARF1-GDP-GEF complex represented well-tolerance. Taken together, 7 had the potential to be served as an effective antileukemia agent or lead compound for further exploration.

Polycomb-like 2 regulates PRC2 components to affect proliferation in glioma cells.

INTRODUCTION: The Polycomb group (PcG) is an important family of transcriptional regulators that controls growth and tumorigenesis. The PcG mainly consists of two complexes, PRC1 and Polycomb Repressive Complex 2 (PRC2). Polycomb-like 2 (PCL2) is known to interact with the PRC2 protein. The role of PCL2 in the development and progression of glioma is unclear. METHODS: We use The Cancer Genome Atlas (TCGA) database to detect the expression of PCL2 in various tumors. 117 cases of clinical glioma (WHOI-IV) were collected, and PCL2 expression and localization were detected by immunohistochemical staining. Glioma cells U87/U251 were infected with overexpressed and interfered PCL2. CCK8 assay, colony formation assay, EdU method, cell cycle and apoptosis were used to detect cell proliferation and apoptosis. Western blot was used to detect the expression of PRC2-related core proteins. After DZNeP intervention, PRC2 protein expression was again measured to discuss the mechanism of PCL2 action. RESULTS: TCGA database results and immunohistochemical staining results suggest that PCL2 is highly expressed in gliomas. We found that the PCL2 gene promoted tumor cell proliferation, enhanced the colony formation ability, and increased S phase in the cell cycle. The overexpression of PCL2 upregulated the expression levels of EZH2 and EED (two core members of PRC2), decreased the expression of SUZ12, increased the level of H3K27 trimethylation (H3K27me3), H3K4 dimethylation (H3K4me2), and decreased H3K9 dimethylation (H3K9me2). The result after interfering with PCL2 was the opposite. CONCLUSIONS: As an important accessory protein of PRC2, PCL2 can not only change the expression of PRC2 components, but also affect the expression level of Histone methylation. Therefore, PCL2 may be an important hub for regulating the synergy among PRC2 members. This study revealed PCL2 as a new target for tumor research and open up a new avenue for future research in glioma.

Structure-Activity Relationships and Potent Cytotoxic Activities of Terphenyllin Derivatives from a Small Compound Library.

A small library of 120 compounds was established with seventy new alkylated derivatives of the natural product terphenyllin, together with 45 previous reported derivatives and four natural p-terphenyl analogs. The 70 new derivatives were semi-synthesized and evaluated for cytotoxic activities against four cancer cell lines. Interestingly, 2',4''-diethoxyterphenyllin, 2',4,4''-triisopropoxyterphenyllin, and 2',4''-bis(cyclopentyloxy)terphenyllin showed potent activities with IC50 values in a range from 0.13 to 5.51 µM, which were similar to those of the positive control, adriamycin. The preliminary structure-activity relationships indicated that the introduction of alkyl substituents including ethyl, allyl, propargyl, isopropyl, bromopropyl, isopentenyl, cyclopropylmethyl, and cyclopentylmethyl are important for improving the cytotoxicity.

Tunable Electrochemical C-N versus N-N Bond Formation of Nitrogen-Centered Radicals Enabled by Dehydrogenative Dearomatization: Biological Applications.

Herein, an environmentally friendly electrochemical approach is reported that takes advantage of the captodative effect and delocalization effect to generate nitrogen-centered radicals (NCRs). By changing the reaction parameters of the electrode material and feedstock solubility, dearomatization enabled a selective dehydrogenative C-N versus N-N bond formation reaction. Hence, pyrido[1,2-a]benzimidazole and tetraarylhydrazine frameworks were prepared through a sustainable transition-metal- and exogenous oxidant-free strategy with broad generality. Bioactivity assays demonstrated that pyrido[1,2-a]benzimidazoles displayed antimicrobial activity and cytotoxicity against human cancer cells. Compound 21 exhibited good photochemical properties with a large Stokes shift (approximately 130 nm) and was successfully applied to subcellular imaging. A preliminary mechanism investigation and density functional theory (DFT) calculations revealed the possible reaction pathway.

Artemisinin analogue SM934 ameliorates DSS-induced mouse ulcerative colitis via suppressing neutrophils and macrophages.

Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease (IBD) characterized by complicated and relapsing inflammation in the gastrointestinal tract. SM934 is a water-soluble artemisinin analogue that shows anti-inflammatory and immuno-regulatory effects. In this study, we investigated the effects of SM934 on UC both in vivo and in vitro. A mouse model of colitis was established in mice by oral administration of 5% dextran sulfate sodium (DSS). SM934 (3, 10 mg/kg per day, ig) was administered to the mice for 10 days. After the mice were sacrificed, colons, spleens and mesenteric lymph nodes (MLNs) were collected for analyses. We showed that SM934 administration restored DSS-induced body weight loss, colon shortening, injury and inflammation scores. Furthermore, SM934 administration significantly decreased the disease activity index (DAI), histopathological scores, and myeloperoxidase (MPO) activities in colonic tissues. Moreover, SM934 administration dose-dependently decreased the mRNA and protein levels of DSS-induced pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α), and the percentage of macrophages and neutrophils in colon tissues. The effects of SM934 on LPS-stimulated RAW 264.7 cells and THP-1-derived macrophages were examined in vitro. Treatment with SM934 (0.8, 8, 80 µmol/L) dose-dependently decreased the production of pro-inflammatory mediators in LPS-stimulated RAW264.7 cells and THP-1-derived macrophages via inhibiting activation of the NF-κB signaling. Our results reveal the protective effects of SM934 on DSS-induced colitis can be attributed to its suppressing effects on neutrophils and macrophages and its inhibitory role in the NF-κB signaling, suggests that SM934 might be a potential effective drug for ulcerative colitis.

(5R)-5-hydroxytriptolide ameliorates lupus nephritis in MRL/lpr mice by preventing infiltration of immune cells.

(5R)-5-hydroxytriptolide (LLDT-8), a triptolide derivative with low toxicity, was previously reported to have strong immunosuppressive effects both in vitro and in vivo, but it remains unknown whether LLDT-8 has a therapy effect on systemic lupus erythematosus. In this study, we aimed to investigate the therapeutic effects of LLDT-8 on lupus nephritis in MRL/lpr mice, a model of systemic lupus erythematosus. Compared with the vehicle group, different clinical parameters were improved upon LLDT-8 treatment as follows: prolonged life span of mice, decreased proteinuria, downregulated blood urea nitrogen and serum creatinine, reduced glomerular IgG deposits, and ameliorated histopathology. A decreased expression of the inflammatory cytokines IFN-γ, IL-17, IL-6, and TNF-α was also observed in the kidney of LLDT-8 treated MRL/lpr mice. Moreover, infiltration of T cells in the kidney was mitigated after LLDT-8 treatment, corresponding with decreased expression of related chemokines IP-10, Mig, and RANTES in the kidney. The proportion of macrophage and neutrophil cells and related chemokines expression was also reduced in kidneys of LLDT-8-treated mice. In the human proximal tubule epithelial cell line and mouse mesangial cell line, consistent with our in vivo experimental results, LLDT-8 suppressed the expression of related chemokines and IL-6. In summary, LLDT-8 has a therapeutic benefit for lupus nephritis via suppressing chemokine expression and inhibiting immune cell infiltration in kidneys of MRL/lpr mice.

Wind profiling for a coherent wind Doppler lidar by an auto-adaptive background subtraction approach.

Auto-adaptive background subtraction (AABS) is proposed as a denoising method for data processing of the coherent Doppler lidar (CDL). The method is proposed specifically for a low-signal-to-noise-ratio regime, in which the drifting power spectral density of CDL data occurs. Unlike the periodogram maximum (PM) and adaptive iteratively reweighted penalized least squares (airPLS), the proposed method presents reliable peaks and is thus advantageous in identifying peak locations. According to the analysis results of simulated and actually measured data, the proposed method outperforms the airPLS method and the PM algorithm in the furthest detectable range. The proposed method improves the detection range approximately up to 16.7% and 40% when compared to the airPLS method and the PM method, respectively. It also has smaller mean wind velocity and standard error values than the airPLS and PM methods. The AABS approach improves the quality of Doppler shift estimates and can be applied to obtain the whole wind profiling by the CDL.

Analysis of weighted subspace fitting and subspace-based eigenvector techniques for frequency estimation for the coherent Doppler lidar.

Since the periodogram maximum (PM) algorithm fails to provide consistent estimates, more robust techniques are developed, especially in a low signal-to-noise ratio (SNR) regime. The methods are formulated in a subspace fitting-based framework, such as the eigenvector (EV) method and the proposed weighted subspace fitting (WSF) method by introducing an optimal weighting matrix, which exploits the low-rank properties of the covariance matrix of the coherent Doppler lidar echo data. Simulation results reveal that the number of the reliable estimates by the WSF method is more than the other two methods, and the standard deviation is the smallest. Furthermore, the predicted best-fit Gaussian model for the probability density function of the estimates has a narrower spectral width than that of PM and EV methods. Experimental results also validate the simulation results, which show that the WSF approach outperforms the PM and EV algorithms in the furthest detectable range. The proposed method improves the detection range approximately up to 14.2% and 26.6% when compared to the EV method and the PM method, respectively. In conclusion, the proposed method can reduce the statistical uncertainties and enhance the accuracy in wind estimation specifically for a low SNR regime.

PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation.

Autophagosome formation is promoted by the PI3 kinase complex and negatively regulated by myotubularin phosphatases, indicating that regulation of local phosphatidylinositol 3-phosphate (PtdIns3P) levels is important for this early phase of autophagy. Here, we show that the Caenorhabditis elegans myotubularin phosphatase MTM-3 catalyzes PtdIns3P turnover late in autophagy. MTM-3 acts downstream of the ATG-2/EPG-6 complex and upstream of EPG-5 to promote autophagosome maturation into autolysosomes. MTM-3 is recruited to autophagosomes by PtdIns3P, and loss of MTM-3 causes increased autophagic association of ATG-18 in a PtdIns3P-dependent manner. Our data reveal critical roles of PtdIns3P turnover in autophagosome maturation and/or autolysosome formation.

Toll-like receptors: potential targets for lupus treatment.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the loss of tolerance to self-nuclear antigens. Accumulating evidence shows that Toll-like receptors (TLRs), previously proven to be critical for host defense, are implicated in the pathogenesis of autoimmune diseases by recognition of self-molecules. Genome-wide association studies, experimental mouse models and clinical sample studies have provided evidence for the involvement of TLRs, including TLR2/4, TLR5, TLR3 and TLR7/8/9, in SLE pathogenesis. A number of downstream proteins in the TLR signaling cascade (such as MyD88, IRAKs and IFN-α) are identified as potential therapeutic targets for SLE treatment. Numerous antagonists targeting TLR signaling, including oligonucleotides, small molecular inhibitors and antibodies, are currently under preclinical studies or clinical trials for SLE treatment. Moreover, the emerging new manipulation of TLR signaling by microRNA (miRNA) regulation shows promise for the future treatment of SLE.

Therapeutic effects of DZ2002, a reversible SAHH inhibitor, on lupus-prone NZB×NZW F1 mice via interference with TLR-mediated APC response.

AIM: To examine the therapeutic effects and underlying mechanisms of DZ2002, a reversible S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, on lupus-prone female NZB×NZW F1 (NZB/W F1) mice. METHODS: Female NZB/W F1 mice were treated orally with DZ2002 (0.5 mg·kg(-1)·d(-1)) for 11 weeks, and the proteinuria level and body weight were monitored. After the mice ware euthanized, serum biochemical parameters and renal damage were determined. Splenocytes of NZB/W F1 mice were isolated for ex vivo study. Toll-like receptor (TLR)-stimulated human peripheral blood mononuclear cells (PBMCs) or murine bone marrow-derived dendritic cells (BMDCs) were used for in vitro study. RESULTS: Treatment of the mice with DZ2002 significantly attenuated the progression of glomerulonephritis and improved the overall health. The improvement was accompanied by decreased levels of nephritogenic anti-dsDNA IgG2a and IgG3 antibodies, serum IL-17, IL-23p19 and TGF-ß. In ex vivo studies, treatment of the mice with DZ2002 suppressed the development of pathogenic Th17 cells, significantly decreased IL-17, TGF-ß, IL-6, and IL-23p19 production and impeded activation of the STAT3 protein and JNK/NF-κB signaling in splenocytes. DZ2002 (500 µmol/L) significantly suppressed TLR agonists-stimulated up-regulation in IL-6, IL-12p40, TNF-α, and IgG and IgM secretion as well as in HLA-DR and CD40 expression of dendritic cells among human PBMCs in vitro. DZ2002 (100 µmol/L) also significantly suppressed TLR agonists-stimulated up-regulation in IL-6 and IL-23p19 production in murine BMDCs, and prevented Th17 differentiation and suppressed IL-17 secretion by the T cells in a BMDC-T cell co-culture system. CONCLUSION: DZ2002 effectively ameliorates lupus syndrome in NZB/W F1 mice by regulating TLR signaling-mediated antigen presenting cell (APC) responses.

Effects of the "AI-TA" Mobile App With Intelligent Design on Psychological and Related Symptoms of Young Survivors of Breast Cancer: Randomized Controlled Trial.

BACKGROUND: Young women often face substantial psychological challenges in the initial years following cancer diagnosis, leading to a comparatively lower quality of life than older survivors. While mobile apps have emerged as potential interventions, their effectiveness remains inconclusive due to the diversity in intervention types and variation in follow-up periods. Furthermore, there is a particular dearth of evidence regarding the efficacy of these apps' intelligent features in addressing psychological distress with these apps. OBJECTIVE: This study aims to evaluate the effectiveness of a mobile app with intelligent design called "AI-TA" on cancer-related psychological health and ongoing symptoms with a randomized controlled design. METHODS: Women aged 18 to 45 years diagnosed with breast cancer were randomly assigned to the intervention or control group. The intervention was AI-TA, which included 2-way web-based follow-up every 2 weeks. Both intention-to-treat (ITT) and per-protocol (PP) analyses employed repeated measurement analysis of variance. The participants' background features, primary outcomes (psychological distress and frequency, self-efficacy, and social support), and secondary outcomes (quality of life) were measured using multiple instruments at 3 time points (baseline, 1-month intervention, and 3-month intervention). RESULTS: A total of 124 participants were randomly allocated to the control group (n=62, 50%) or intervention group (n=62, 50%). In total, 92.7% (115/124) of the participants completed the intervention. Significant improvements in psychological symptoms (Memorial Symptom Assessment Scale-Short Form) were observed in the ITT group from baseline to 1-month intervention relative to the control group (ITT vs control: 1.17 vs 1.23; P<.001), which persisted at 3-month follow-up (ITT vs control: 0.68 vs 0.91; P<.001). Both the ITT and PP groups exhibited greater improvements in self-efficacy (Cancer Behavior Inventory-Brief Version) than the control group at 1-month (ITT vs PP vs control: 82.83 vs 77.12 vs 65.35; P<.001) and 3-month intervention (ITT vs PP vs control: 92.83 vs 89.30 vs 85.65; P<.001). However, the change in social support (Social Support Rating Scale) did not increase significantly until 3-month intervention (ITT vs control: 50.09 vs 45.10; P=.002) (PP vs control: 49.78 vs 45.10; P<.001). All groups also experienced beneficial effects on quality of life (Functional Assessment of Cancer Therapy-Breast), which persisted at 3-month follow-up (P<.001). CONCLUSIONS: The intelligent mobile app AI-TA incorporating intelligent design shows promise for reducing psychological and cancer-related symptoms among young survivors of breast cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200058823; https://www.chictr.org.cn/showproj.html?proj=151195.

Imaging Valley Excitons in a 2D Semiconductor with Scanning Tunneling Microscope-Induced Luminescence.

Valley excitons dominate the optoelectronic response of transition-metal dichalcogenides and are drastically affected by structural and environmental inhomogeneities localized in these materials. Critical to understanding and controlling these nanoscale excitonic changes is the ability to correlate the imaging of excitonic states with crystalline structures on the atomic scale. Here, we apply scanning tunneling microscope-induced luminescence microscopy to image valley excitons in a semiconducting transition-metal dichalcogenide monolayer decoupled by a 10 nanometer-thick hexagonal-boron-nitride flake incorporated in a lateral homojunction on an Au electrode surface. This design enables the observation of chiral excitonic emission arising from neutral and charged valley excitons of the monolayer semiconductor at ambipolar voltages with a quantum efficiency up to ∼10-5 photon/electron. The measured light helicity demonstrates considerable circular polarization dependent on the sample voltage, reaching as much as 40%. The real-space luminescence imaging maps─at subnanometer resolution─of the valley excitons reveal striking spatial variations associated with localized inhomogeneities, including surface impurities and possibly nanoscale dielectric and/or potential disorders in the monolayer. Our study introduces a promising format for 2D materials to explore and tailor their optoelectronic processes at the atomic scale.