Effectiveness of instant versus text messaging intervention on antiretroviral therapy adherence among men who have sex with men living with HIV.

Objective: This study aimed to compare the effectiveness of instant versus text messaging intervention (TMI) on antiretroviral therapy (ART) adherence among men who have sex with men (MSM) living with HIV. Methods: This study was conducted in an infectious disease hospital of Jinan, China from October 2020 to June 2021, using non-randomized concurrent controlled design to compare the effectiveness of instant messaging intervention (IMI) versus TMI. The intervention strategies (health messaging, medication reminder, and peer education) and contents were consistent between the two groups, and the difference was service delivery method and type of information. The primary outcome was the proportion of achieving optimal ART adherence, defined as never missing any doses and delayed any doses more than 1 hour. Results: A total of 217 participants (including 72 in TMI group and 145 in IMI group) were included in the study. The proportion of achieving optimal adherence was higher in IMI group than TMI group at the first follow-up (90.2% versus 77.6%, p = 0.021) and second follow-up (86.5% versus 76.6%, p = 0.083). The effect of IMI versus TMI on improving ART adherence was found not to be statistically significant (risk ratio (RR) = 1.93, 95% confidence interval (CI): 0.95-3.94) in complete-case analysis. However, when excluding participants who did not adhere to the interventions, a significant improvement was observed (RR = 2.77, 95%CI: 1.21-6.38). More participants in IMI group expressed highly rated satisfaction to the intervention services than those in TMI group (67.3% versus 50.0%). Conclusions: The IMI demonstrated superior efficacy over TMI in improving ART adherence and satisfaction with intervention services. It is suggested that future digital health interventions targeting ART adherence should prioritize instant messaging with multimedia information in areas with Internet access. Trial registration: The study was registered at the Chinese Clinical Trial Register (ChiCTR), with number [ChiCTR2000041282].

Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment.

ABSTRACT: Poststroke cognitive impairment is a major secondary effect of ischemic stroke in many patients; however, few options are available for the early diagnosis and treatment of this condition. The aims of this study were to (1) determine the specific relationship between hypoxic and α-synuclein during the occur of poststroke cognitive impairment and (2) assess whether the serum phosphorylated α-synuclein level can be used as a biomarker for poststroke cognitive impairment. We found that the phosphorylated α-synuclein level was significantly increased and showed pathological aggregation around the cerebral infarct area in a mouse model of ischemic stroke. In addition, neuronal α-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia, suggesting that hypoxia is the underlying cause of α-synuclein-mediated pathology in the brains of mice with ischemic stroke. Serum phosphorylated α-synuclein levels in patients with ischemic stroke were significantly lower than those in healthy subjects, and were positively correlated with cognition levels in patients with ischemic stroke. Furthermore, a decrease in serum high-density lipoprotein levels in stroke patients was significantly correlated with a decrease in phosphorylated α-synuclein levels. Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury, some of them exhibited decreased cognitive function and reduced phosphorylated α-synuclein levels. Taken together, our results suggest that serum phosphorylated α-synuclein is a potential biomarker for poststroke cognitive impairment.

Representation and computation in visual working memory.

The ability to sustain internal representations of the sensory environment beyond immediate perception is a fundamental requirement of cognitive processing. In recent years, debates regarding the capacity and fidelity of the working memory (WM) system have advanced our understanding of the nature of these representations. In particular, there is growing recognition that WM representations are not merely imperfect copies of a perceived object or event. New experimental tools have revealed that observers possess richer information about the uncertainty in their memories and take advantage of environmental regularities to use limited memory resources optimally. Meanwhile, computational models of visuospatial WM formulated at different levels of implementation have converged on common principles relating capacity to variability and uncertainty. Here we review recent research on human WM from a computational perspective, including the neural mechanisms that support it.

Prehabilitation of surgical patients: a bibliometric analysis from 2005 to 2023.

BACKGROUND: Good preoperative conditions help patients to counteract surgical injury. Prehabilitation is a multimodal preoperative management strategy, including physical, nutritional, psychological, and other interventions, which can improve the functional reserve of patients and enhance postoperative recovery. The purpose of this study is to show the evolution trend and future directions of research related to the prehabilitation of surgical patients. METHODS: The global literature regarding prehabilitation was identified from The Web of Science Core Collection database. Bibliometric methods of the Bibliometrix package of R (version 4.2.1) and VOSviewer were used to analyze publication trends, cooperative networks, study themes, and co-citation relationships in the field. RESULTS: A total of 638 publications were included and the number of publications increased rapidly since 2016, with an average annual growth rate of 41.0%. "Annals of Surgery", "British Journal of Surgery" and "British Journal of Anesthesia" were the most cited journals. Experts from the USA, Canada, the UK, and the Netherlands contributed the most in this field, and an initial cooperative network among different countries and clinical teams was formed. Malnutrition, older patients, frailty, and high-risk patients were the hotspots of recent studies. However, among the top 10 cited articles, the clinical effects of prehabilitation were conflicting. CONCLUSION: This bibliometric review summarized the most influential publications as well as the publication trends and clarified the progress and future directions of prehabilitation, which could serve as a guide for developing evidence-based practices.

Intrinsically stretchable organic photovoltaics by redistributing strain to PEDOT:PSS with enhanced stretchability and interfacial adhesion.

Intrinsically stretchable organic photovoltaics have emerged as a prominent candidate for the next-generation wearable power generators regarding their structural design flexibility, omnidirectional stretchability, and in-plane deformability. However, formulating strategies to fabricate intrinsically stretchable organic photovoltaics that exhibit mechanical robustness under both repetitive strain cycles and high tensile strains remains challenging. Herein, we demonstrate high-performance intrinsically stretchable organic photovoltaics with an initial power conversion efficiency of 14.2%, exceptional stretchability (80% of the initial power conversion efficiency maintained at 52% tensile strain), and cyclic mechanical durability (95% of the initial power conversion efficiency retained after 100 strain cycles at 10%). The stretchability is primarily realised by delocalising and redistributing the strain in the active layer to a highly stretchable PEDOT:PSS electrode developed with a straightforward incorporation of ION E, which simultaneously enhances the stretchability of PEDOT:PSS itself and meanwhile reinforces the interfacial adhesion with the polyurethane substrate. Both enhancements are pivotal factors ensuring the excellent mechanical durability of the PEDOT:PSS electrode, which further effectively delays the crack initiation and propagation in the top active layer, and enables the limited performance degradation under high tensile strains and repetitive strain cycles.

PRDX1 exerts a photoprotection effect by inhibiting oxidative stress and regulating MAPK signaling on retinal pigment epithelium.

BACKGROUND: The purpose of this study was to investigate the photoprotection effect of peroxiredoxin 1 (PRDX1) protein in ultraviolet B (UVB) irradiation-induced damage of retinal pigment epithelium (RPE) and its possible molecular mechanism. METHODS: ARPE-19 cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the PRDX1 expression. The corresponding kits were employed to measure the levels or activities of lactate dehydrogenase (LDH), 8-hydroxy-2-deoxyguanosine (8-OHdG), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD). Western blotting was applied to examine PRDX1 expression and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. RESULTS: After exposure to 20 mJ/cm2 intensity of UVB irradiation for 24 h, ARPE-19 cells viability was decreased, the leakage degree of LDH and 8-OHdG were increased, and cell apoptosis was elevated. The expression of PRDX1 was significantly down-regulated in UVB-induced ARPE-19 cells. The low expression of PRDX1 was involved in high irradiation intensity. Overexpression of PRDX1 increased cell activity, decreased cell apoptosis, and LDH as well as 8-OHdG leakage in UVB-induced ARPE-19 cells. In addition to alleviating UVB-induced cell damage, PRDX1 overexpression also inhibited UVB-induced oxidative stress (down-regulation of ROS and MDA levels, up-regulation of GSH-Px and SOD activities) and the activation of MAPK signaling pathway in ARPE-19 cells. CONCLUSION: PRDX1 exerts a photoprotection effect on RPE by attenuating UVB-induced cell damage and inhibiting oxidative stress, which can be attributed to the inhibition of MAPK signaling pathway activation.

Clinical analysis of 314 patients with high-grade squamous intraepithelial lesion who underwent total hysterectomy directly: a multi-center, retrospective cohort study.

OBJECTIVE: To identify the risk factors of cervical high-grade squamous intraepithelial lesion(HSIL) complicated with occult cervical cancer and standardize the management of initial treatment for HSIL. METHOD: The clinical data of patients who underwent total hysterectomy directly due to HSIL in the obstetrics and gynecology department of two tertiary hospitals and three secondary hospitals from 2018 to 2023 were collected. Their general characteristics, pathological parameters and survival status were analyzed. Logistic regression model was used to analyze the correlation between clinical parameters and postoperative pathological upgrading. RESULT: 1. Among the 314 patients with HSIL who underwent total hysterectomy directly, 73.2% were from primary hospitals. 2. 25 patients (7.9%) were pathologically upgraded to cervical cancer, all of which were early invasive cancer. 3. Up to now, there was no recurrence or death in the 25 patients with early-stage invasive cancer, and the median follow-up period was 21 months(range 2-59 months). 4. Glandular involvement(OR 3.968; 95%CI 1.244-12.662) and lesion range ≥ 3 quadrants (OR 6.527; 95% CI 1.78-23.931), HPV 16/18 infection (OR 5.382; 95%CI 1.947-14.872), TCT ≥ ASC-H (OR 4.719; 95%CI 1.892-11.766) were independent risk factors that affected the upgrading of postoperative pathology. 5. The area under the curve (AUC) calculated by the Logistic regression model was 0.840, indicating that the predictive value was good. CONCLUSION: There is a risk of occult cervical cancer in patients with HSIL. Glandular involvement, Lesion range ≥ 3 quadrants, HPV 16/18 infection and TCT ≥ ASC-H are independent risk factors for HSIL combined with occult cervical cancer. The prognosis of biopsy-proved HSIL patients who underwent extrafascial hysterectomy and unexpected early invasive cancer was later identified on specimen may be good.

Targeting selective autophagy and beyond: From underlying mechanisms to potential therapies.

BACKGROUND: Autophagy is an evolutionarily conserved turnover process for intracellular substances in eukaryotes, relying on lysosomal (in animals) or vacuolar (in yeast and plants) mechanisms. In the past two decades, emerging evidence suggests that, under specific conditions, autophagy can target particular macromolecules or organelles for degradation, a process termed selective autophagy. Recently, accumulating studies have demonstrated that the abnormality of selective autophagy is closely associated with the occurrence and progression of many human diseases, including neurodegenerative diseases, cancers, metabolic diseases, and cardiovascular diseases. AIM OF REVIEW: This review aims at systematically and comprehensively introducing selective autophagy and its role in various diseases, while unravelling the molecular mechanisms of selective autophagy. By providing a theoretical basis for the development of related small-molecule drugs as well as treating related human diseases, this review seeks to contribute to the understanding of selective autophagy and its therapeutic potential. KEY SCIENTIFIC CONCEPTS OF REVIEW: In this review, we systematically introduce and dissect the major categories of selective autophagy that have been discovered. We also focus on recent advances in understanding the molecular mechanisms underlying both classical and non-classical selective autophagy. Moreover, the current situation of small-molecule drugs targeting different types of selective autophagy is further summarized, providing valuable insights into the discovery of more candidate small-molecule drugs targeting selective autophagy in the future. On the other hand, we also reveal clinically relevant implementations that are potentially related to selective autophagy, such as predictive approaches and treatments tailored to individual patients.

The association between humidex and tuberculosis: a two-stage modelling nationwide study in China.

BACKGROUND: Under a changing climate, the joint effects of temperature and relative humidity on tuberculosis (TB) are poorly understood. To address this research gap, we conducted a time-series study to explore the joint effects of temperature and relative humidity on TB incidence in China, considering potential modifiers. METHODS: Weekly data on TB cases and meteorological factors in 22 cities across mainland China between 2011 and 2020 were collected. The proxy indicator for the combined exposure levels of temperature and relative humidity, Humidex, was calculated. First, a quasi-Poisson regression with the distributed lag non-linear model (DLNM) was constructed to examine the city-specific associations between humidex and TB incidence. Second, a multivariate meta-regression model was used to pool the city-specific effect estimates, and to explore the potential effect modifiers. RESULTS: A total of 849,676 TB cases occurred in the 22 cities between 2011 and 2020. Overall, a conspicuous J-shaped relationship between humidex and TB incidence was discerned. Specifically, a decrease in humidex was positively correlated with an increased risk of TB incidence, with a maximum relative risk (RR) of 1.40 (95% CI: 1.11-1.76). The elevated RR of TB incidence associated with low humidex (5th humidex) appeared on week 3 and could persist until week 13, with a peak at approximately week 5 (RR: 1.03, 95% CI: 1.01-1.05). The effects of low humidex on TB incidence vary by Natural Growth Rate (NGR) levels. CONCLUSION: A J-shaped exposure-response association existed between humidex and TB incidence in China. Humidex may act as a better predictor to forecast TB incidence compared to temperature and relative humidity alone, especially in regions with higher NGRs.

Tumour necrosis factor α regulates the miR-27a-3p-Sfrp1 axis in a mouse model of osteoporosis.

Osteoporosis is a metabolic bone disease that involves gradual loss of bone density and mass, thus resulting in increased fragility and risk of fracture. Inflammatory cytokines, such as tumour necrosis factor α (TNF-α), inhibit osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and several microRNAs are implicated in osteoporosis development. This study aimed to explore the correlation between TNF-α treatment and miR-27a-3p expression in BMSC osteogenesis and further understand their roles in osteoporosis. An osteoporosis animal model was established using ovariectomized (OVX) mice. Compared with Sham mice, the OVX mice had a significantly elevated level of serum TNF-α and decreased level of bone miR-27a-3p, and in vitro TNF-α treatment inhibited miR-27a-3p expression in BMSCs. In addition, miR-27a-3p promoted osteogenic differentiation of mouse BMSCs in vitro, as evidenced by alkaline phosphatase staining and Alizarin Red-S staining, as well as enhanced expression of the osteogenic markers Runx2 and Osterix. Subsequent bioinformatics analysis combined with experimental validation identified secreted frizzled-related protein 1 (Sfrp1) as a downstream target of miR-27a-3p. Sfrp1 overexpression significantly inhibited the osteogenic differentiation of BMSCs in vitro and additional TNF-α treatment augmented this inhibition. Moreover, Sfrp1 overexpression abrogated the promotive effect of miR-27a-3p on the osteogenic differentiation of BMSCs. Furthermore, the miR-27a-3p-Sfrp1 axis was found to exert its regulatory function in BMSC osteogenic differentiation via regulating Wnt3a-ß-catenin signalling. In summary, this study revealed that TNF-α regulated a novel miR-27a-3p-Sfrp1 axis in osteogenic differentiation of BMSCs. The data provide new insights into the development of novel therapeutic strategies for osteoporosis.

Mitochondrial Sirtuins in Cancer: A Revisited Review from Molecular Mechanisms to Therapeutic Strategies.

The sirtuin (SIRT) family is well-known as a group of deacetylase enzymes that rely on nicotinamide adenine dinucleotide (NAD+). Among them, mitochondrial SIRTs (SIRT3, SIRT4, and SIRT5) are deacetylases located in mitochondria that regulate the acetylation levels of several key proteins to maintain mitochondrial function and redox homeostasis. Mitochondrial SIRTs are reported to have the Janus role in tumorigenesis, either tumor suppressive or oncogenic functions. Although the multi-faceted roles of mitochondrial SIRTs with tumor-type specificity in tumorigenesis, their critical functions have aroused a rising interest in discovering some small-molecule compounds, including inhibitors and activators for cancer therapy. Herein, we describe the molecular structures of mitochondrial SIRTs, focusing on elucidating their regulatory mechanisms in carcinogenesis, and further discuss the recent advances in developing their targeted small-molecule compounds for cancer therapy. Together, these findings provide a comprehensive understanding of the crucial roles of mitochondrial SIRTs in cancer and potential new therapeutic strategies.

Biomimetic Photonic Elastomer Exhibiting Stress/Moisture Reconfigurable Wrinkle-Lattice for Reversible Deformation Information Storage.

Photonic elastomers, capable of converting imperceptible deformations into visible colors, show significant potential in smart materials. However, instantaneous deformation is arduous to record accurately due to the disappearance of optical information after deformation recovery. Herein, inspired by the folding structures of iridocytes in cephalopods, a stress- and moisture-triggered wrinkling and erasure effect is proposed to be introduced in the construction of a photonic elastomer. Implemented in a dual-network polymer framework with modulatable locking, it allows for reversible deformation storage. The photonic elastomer comprises a surface one-dimensional photonic crystal (1DPC) and a poly(dimethylsiloxane) (PDMS) substrate. The deformed 1DPC lattice transforms into a wrinkled state due to a substrate deformation mismatch, preserving strain-induced structural color information through interchain hydrogen bonding and crystalline shape-locking in dual-network polymers. Reading the color provides multidimensional information about the instantaneous deformation degree and distribution. Moreover, the moisture-induced shape-memory feature of the 1DPC can be triggered with a minute amount of water, like fingertip perspiration or humidity change (35% to 80%), to restore the original color. This stress/moisture-responsive photonic elastomer, with its dynamically reconfigurable wrinkle-lattice, holds great promise for applications in mechanical sensing, inkless writing, and anticounterfeiting, significantly enhancing the versatility of photonic materials.

Efficient optimization of an accelerator neutron source for neutron capture therapy using genetic algorithms.

BACKGROUND: In recent years, genetic algorithms have been applied in the field of nuclear technology design, producing superior optimization results compared to traditional methods. They can be employed in the design and optimization of beam shaping assemblies (BSA) BSA to obtain the desired neutron beams. But it should be noted that the direct combination of Monte Carlo methods with genetic algorithms requires a significant amount of computational resources and time. PURPOSE: Design and optimize BSA more efficiently to achieve neutron beams that meet specified recommendations. METHODS: We propose an approach of NSGA II with crucial variables which are identified by multivariate statistical techniques. This approach significantly reduces the problem sizes, thus reducing the time required for optimization. We illustrate this methodology using the example of BSA design for AB-BNCT. RESULTS: The computational efficiency has tripled with crucial variables. By using NSGA II, we obtained optimized models conforming to both the new and old version IAEA BNCT guidelines through a single optimization process and subjected them to phantom analysis. The results demonstrate that models obtained through this method can meet the IAEA recommendations with deep advantage depth (AD) and high absorbed ratio (AR). CONCLUSION: The genetic algorithm with crucial variables displays tremendous potential in addressing BSA optimization challenges.

Genome-wide identification and expression pattern analysis of the GRF transcription factor family in Astragalus mongholicus.

BACKGROUND: Astragalus membranaceus is a plant of the Astragalus genus, which is used as a traditional Chinese herbal medicine with extremely high medicinal and edible value. Astragalus mongholicus, as one of the representative medicinal materials with the same origin of medicine and food, has a rising market demand for its raw materials, but the quality is different in different production areas. Growth-regulating factors (GRF) are transcription factors unique to plants that play important roles in plant growth and development. Up to now, there is no report about GRF in A. mongholicus. METHODS AND RESULTS: This study conducted a genome-wide analysis of the AmGRF gene family, identifying a total of nine AmGRF genes that were classified into subfamily V based on phylogenetic relationships. In the promoter region of the AmGRF gene, we successfully predicted cis-elements that respond to abiotic stress, growth, development, and hormone production in plants. Based on transcriptomic data and real-time quantitative polymerase chain reaction (qPCR) validation, the results showed that AmGRFs were expressed in the roots, stems, and leaves, with overall higher expression in leaves, higher expression of AmGRF1 and AmGRF8 in roots, and high expression levels of AmGRF1 and AmGRF9 in stems. CONCLUSIONS: The results of this study provide a theoretical basis for the further exploration of the functions of AmGRFs in plant growth and development.

Presence of CoV-2 antibody in vitreous humor after Cov-2 infection.

Purpose: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a life-threatening disease with largely unknown intraocular pathogenesis. Herein, we determined the presence of SARS-CoV-2-specific ribonucleic acid (RNA) and virus-associated antibodies in the vitreous humor of people who have recently recovered from SARS-CoV-2 infection. Design: This cross-sectional study included 33 patients (33 eyes) who have recently recovered from SARS-CoV-2 infection. Vitreous humor and blood serum samples were tested for the SARS-CoV-2 RNA and virus-associated antibodies. Results: Among 33 participants, blood serum and vitreous humor were all tested negative for SARS-CoV-2 RNA. SARS-CoV-2-specific IgM was detected in 87.88 % (29/33) patients in blood serum and 6.10 % (2/33) in vitreous humor; SARS-CoV-2-specific IgG was detected in 96.97 % (32/33) patient in blood serum and 81.82 % (27/33) in vitreous humor. Statistical significance was found for IgM expression between blood serum and vitreous humor (P < 0.01), while IgG was not (P = 0.11). The days after recovery were statistically longer both in IgM-positive blood serum samples group and IgG-positive vitreous humor samples group compared with negative samples of each group (P < 0.01). Additionally, no statistical difference could be detected in antibody expression in vitreous humor between different groups divided on the condition of the risk of blood-retina-barrier (BRB) failure (P = 0.49 for IgM; P = 0.37 for IgG). Conclusion: After recovering from COVID-19, no SARS-CoV-2 RNA was detected in vitreous humor, but anti-CoV-2 IgM was detected in 6.1 % and IgG in approximately 80 % of vitreous humor samples of participants. We also found that the positivety rate of SARS-CoV-2-specific antibodies in the blood serum and vitreous humor were both correlated with the days after recovery since the infection.

The Comparison of Lifestyles, Mental Risks, and Physical Indices among Individuals with Ultra-High Risk of Psychosis, Patients with Schizophrenia, and the General Public.

(1) Background: Early interventions may effectively reduce the risk of mental disorders in individuals with ultra-high risk. Specifying the health needs of individuals with ultra-high risk is crucial before the implementation of successful early intervention. This study aimed to explore the differences in lifestyles, mental risks, and physical indices among individuals with ultra-high risk, patients with schizophrenia, and healthy subjects. (2) Methods: A cross-section design applying seven questionnaires with physical examinations for 144 participants aged 13-45 years old was conducted in this study. The questionnaires included one about personal data, four on mental risks, and two for lifestyles. (3) Results: The individuals with ultra-high risk scored similarly in many dimensions as the patients with schizophrenia, but they displayed lower positive symptoms, lower negative symptoms, lower prodromal symptoms, higher interpersonal deficits, lower nutrition intake, and higher levels of exercise than the patients with schizophrenia. Female individuals with ultra-high risk had lower self-esteem, higher positive symptoms, lower nutrition intake, and higher exercise levels than male ones. (4) Conclusions: The study pinpointed specific health needs with interpersonal deficits, nutrition intake, and physical activity for the individuals with ultra-high risk. Future interventions targeted on improving social function, dietary pattern, and exercise will be beneficial.

Robustness of response-adaptive randomization.

Doubly adaptive biased coin design (DBCD), a response-adaptive randomization scheme, aims to skew subject assignment probabilities based on accrued responses for ethical considerations. Recent years have seen substantial advances in understanding DBCD's theoretical properties, assuming correct model specification for the responses. However, concerns have been raised about the impact of model misspecification on its design and analysis. In this paper, we assess the robustness to both design model misspecification and analysis model misspecification under DBCD. On one hand, we confirm that the consistency and asymptotic normality of the allocation proportions can be preserved, even when the responses follow a distribution other than the one imposed by the design model during the implementation of DBCD. On the other hand, we extensively investigate three commonly used linear regression models for estimating and inferring the treatment effect, namely difference-in-means, analysis of covariance (ANCOVA) I, and ANCOVA II. By allowing these regression models to be arbitrarily misspecified, thereby not reflecting the true data generating process, we derive the consistency and asymptotic normality of the treatment effect estimators evaluated from the three models. The asymptotic properties show that the ANCOVA II model, which takes covariate-by-treatment interaction terms into account, yields the most efficient estimator. These results can provide theoretical support for using DBCD in scenarios involving model misspecification, thereby promoting the widespread application of this randomization procedure.

Integrated multi-omics profiling reveals a clinically relevant molecular feature and potential therapeutic target on phyllodes tumors of breast.

Phyllodes tumors (PTs) has an increased risk of local relapse and distant metastases. Molecular features correlating to histologic grade and aggressive behavior of PTs are poorly characterized. Here, whole exome sequencing (WES) was performed to explore genetic mutations in 61 samples of fibroepithelial breast tumors, including 16 fibroadenomas (FAs), 18 benign PTs, 19 borderline PTs, and 8 malignant PTs. Our work clearly shows that FA, benign PT, borderline PT, and malignant PT are independent entities at the genomic level. They may exist as hidden sub-clones carrying specific genetic alterations. Malignant PT-specific mutations present a multi-gene co-mutational pattern suggesting a synergistic effect of co-mutated genes in processes associated with malignant behavior. Moreover, we made a combined genomic and transcriptomic analysis, which presented a mutated gene-based interaction with expression profiles. We found that EGFR mutations (c.710C > T, c.758A > G, c.1295A > G, and c.2156G > C) serve as a hub of interaction network in borderline PTs, which suggests EGFR tyrosine kinase inhibitors (EGFRi) might be effective for borderline PTs. We found TP53 mutations (c.730G > T, c.844C > T, and c.1019delA) serves as a hub event of molecular changes of malignant PTs. Thus, our study based on the omics platforms of genome and transcriptome provides a better understanding of relapse process and the potential targeted therapy in PTs, which is pivotal in improving molecular-guided patient selection and designing clinically relevant combination strategies.

A Difluoro-Methoxylated Ending-Group Asymmetric Small Molecule Acceptor Lead Efficient Binary Organic Photovoltaic Blend.

Developing a new end group for synthesizing asymmetric small molecule acceptors (SMAs) is crucial for achieving high-performance organic photovoltaics (OPVs). Herein, an asymmetric small molecule acceptor, BTP-BO-4FO, featuring a new difluoro-methoxylated end-group is reported. Compared to its symmetric counterpart L8-BO, BTP-BO-4FO exhibits an upshifted energy level, larger dipole moment, and more sequential crystallinity. By adopting two representative and widely available solvent additives (1-chloronaphthalene (CN) and 1,8-diiodooctane (DIO)), the device based on PM6:BTP-BO-4FO (CN) photovoltaic blend demonstrates a power conversion efficiency (PCE) of 18.62% with an excellent open-circuit voltage (VOC) of 0.933 V, which surpasses the optimal result of L8-BO. The PCE of 18.62% realizes the best efficiencies for binary OPVs based on SMAs with asymmetric end groups. A series of investigations reveal that optimized PM6:BTP-BO-4FO film demonstrates similar molecular packing motif and fibrillar phase distribution as PM6:L8-BO (DIO) does, resulting in comparable recombination dynamics, thus, similar fill factor. Besides, it is found PM6:BTP-BO-4FO possesses more efficient charge generation, which yields better VOC-JSC balance. This study provides a new ending group that enables a cutting-edge efficiency in asymmetric SMA-based OPVs, enriching the material library and shed light on further design ideas.