BRCA1 secondary splice-site mutations drive exon-skipping and PARP inhibitor resistance.

PARP inhibitor (PARPi) therapy has transformed outcomes for patients with homologous recombination DNA repair (HRR) deficient ovarian cancers, for example those with BRCA1 or BRCA2 gene defects. Unfortunately, PARPi resistance is common. Multiple resistance mechanisms have been described, including secondary mutations that restore the HR gene reading frame. BRCA1 splice isoforms △11 and △11q can contribute to PARPi resistance by splicing out the mutation-containing exon, producing truncated, partially functional proteins. However, the clinical impacts and underlying drivers of BRCA1 exon skipping are not fully understood.We analyzed nine ovarian and breast cancer patient derived xenografts (PDX) with BRCA1 exon 11 frameshift mutations for exon skipping and therapy response, including a matched PDX pair derived from a patient pre- and post-chemotherapy/PARPi. BRCA1 exon 11 skipping was elevated in PARPi resistant PDX tumors. Two independent PDX models acquired secondary BRCA1 splice site mutations (SSMs) that drive exon skipping, confirmed using qRT-PCR, RNA sequencing, immunoblotting and minigene modelling. CRISPR/Cas9-mediated disruption of splicing functionally validated exon skipping as a mechanism of PARPi resistance. SSMs were also enriched in post-PARPi ovarian cancer patient cohorts from the ARIEL2 and ARIEL4 clinical trials.Few PARPi resistance mechanisms have been confirmed in the clinical setting. While secondary/reversion mutations typically restore a gene's reading frame, we have identified secondary mutations in patient cohorts that hijack splice sites to enhance mutation-containing exon skipping, resulting in the overexpression of BRCA1 hypomorphs, which in turn promote PARPi resistance. Thus, BRCA1 SSMs can and should be clinically monitored, along with frame-restoring secondary mutations.

Enzyme-free method for preparation of sturgeon extracts with antioxidant, hepatoprotective and immune-enhancing functions.

Sturgeon has a long lifespan and slow evolutionary rate due to their powerful endogenous antioxidant system. This work aimed to assess the in vitro and in vivo antioxidant activity of sturgeon extracts from both muscle and roe. The extraction process without enzyme hydrolysis is not only simple, but also can produce extracts with better free radicals scavenging abilities than enzymatic hydrolysates in both cellular and in vivo experiments. Moreover, in mouse models with liver injury and immunosuppression treatment, the sturgeon extracts demonstrated strong hepatoprotective and immune-enhancing functions, comparable to vitamin C and ginseng extract supplements, which were attributed to abundant antioxidant peptides of the extracts. The 15 isolated peptides exhibited diverse free radical scavenging ability. Therefore, the sturgeon extracts showed high potential to be applied in food and biomedical industries.

High-level tumour methylation of BRCA1 and RAD51C is required for homologous recombination deficiency in solid cancers.

In ovarian and breast cancer, promoter methylation of BRCA1 or RAD51C is a promising biomarker for PARP inhibitor response, as high levels lead to homologous recombination deficiency (HRD). Yet the extent and role of such methylation in other cancers is not clear. This study comprehensively investigated promoter methylation of eight homologous recombination repair genes across 23 solid cancer types. Here, we showed that BRCA1 methylated cancers were associated with reduced gene expression, loss of heterozygosity (LOH), TP53 mutations and genomic features of HRD. We identified BRCA1 methylation in 3% of the copy-number high subtype of endometrial cancer, and as a rare event in six other cancer types, including lung squamous cell, pancreatic, bladder and stomach cancer. RAD51C promoter methylation was widespread across multiple cancer types, but HRD features were only observed for cases which contained high-level tumour methylation and LOH of RAD51C. While RAD51C methylation was frequent in stomach adenocarcinoma (6%) and low-grade glioma (2.5%), it was mostly detected at a low tumour level, suggestive of heterozygous methylation, and was associated with CpG island methylator phenotype. Our findings indicate that high-level tumour methylation of BRCA1 and RAD51C should be explored as a PARP inhibitor biomarker across multiple cancers.

Spectral analysis enhanced net (SAE-Net) to classify breast lesions with BI-RADS category 4 or higher.

Early ultrasound screening for breast cancer reduces mortality significantly. The main evaluation criterion for breast ultrasound screening is the Breast Imaging-Reporting and Data System (BI-RADS), which categorizes breast lesions into categories 0-6 based on ultrasound grayscale images. Due to the limitations of ultrasound grayscale imaging, lesions with categories 4 and 5 necessitate additional biopsy for the confirmation of benign or malignant status. In this paper, the SAE-Net was proposed to combine the tissue microstructure information with the morphological information, thus improving the identification of high-grade breast lesions. The SAE-Net consists of a grayscale image branch and a spectral pattern branch. The grayscale image branch used the classical deep learning backbone model to learn the image morphological features from grayscale images, while the spectral pattern branch is designed to learn the microstructure features from ultrasound radio frequency (RF) signals. Our experimental results show that the best SAE-Net model has an area under the receiver operating characteristic curve (AUROC) of 12% higher and a Youden index of 19% higher than the single backbone model. These results demonstrate the effectiveness of our method, which potentially optimizes biopsy exemption and diagnostic efficiency.

Further screening of SNP loci of eggshell translucency related genes and evaluation of genetic effects.

Eggshell translucency is a widespread issue in the field of egg quality. Previous research has established that the heritability of eggshell translucency is relatively low or moderate. Scientists have also successfully identified SNP loci related to eggshell translucency on different chromosomes by using gene chips and single-variant GWAS. However, the specific impact of single or multiple genes on the trait of eggshell translucency remains unknown. In an effort to investigate this, we examined 170 SNPs associated with eggshell translucency obtained by our research group. We selected 966 half-sibling laying hens from 2 generations in 3 pure lines: Dwarf Layer-White, Rhode Island Red-White Strain, and Rhode Island Red. Eggs were collected from each hen over a period of 5 consecutive days, and eggshell translucency was measured using a grading method in which the hens were divided into 2 groups: an opaque group and a translucent group. We collected blood samples from the laying hens and extracted DNA. Time of flight mass spectrometry (TOF-MS) was used for genotyping to identify SNP loci that influence the trait of eggshell translucency. The results of our analysis revealed that using TOF-MS in 3 chicken strains, we were able to eliminate loci with low gene polymorphism, genetic effect contribution less than 1%, and deviation from Hardy-Weinberg equilibrium. Ultimately, 5 SNPs (Affx-50362599, rs15050262, rs312943734, rs316121113, and rs317389181) were identified on chromosomes 1, 5, and 19. Additionally, nine candidate genes (DCN, BTG1, ZFP92, POU2F1, NUCB2, FTL, GGNBP2, ACACA, and TADA2A) were found to be associated with these SNPs. No linkage disequilibrium relationship was observed between the 2 pairs of SNP loci on chromosomes 1 and 19. Based on previous studies on the formation mechanism of eggshell translucency, we hypothesize that NUCB2, FTL, and ACACA genes may be affecting the eggshell structure through different mechanisms, such as increase the water permeability or make thin of eggshell membrane, which promote moisture or part of other egg contents and ultimately lead to the formation of eggshell translucency. These findings validate and identify five SNP loci that regulate the translucency trait, and provide molecular markers for breeding non-translucent populations. Furthermore, this study serves as a reference for further investigation of the genetic regulatory mechanisms underlying eggshell translucency.

Osteoblast-specific down-regulation of NLRP3 inflammasome by aptamer-functionalized liposome nanoparticles improves bone quality in postmenopausal osteoporosis rats.

Rationale: NLRP3 inflammasome is critical in the development and progression of many metabolic diseases driven by chronic inflammation, but its effect on the pathology of postmenopausal osteoporosis (PMOP) remains poorly understood. Methods: We here firstly examined the levels of NLRP3 inflammasome in PMOP patients by ELISA. Then we investigated the possible mechanisms underlying the effect of NLRP3 inflammasome on PMOP by RNA sequencing of osteoblasts treated with NLRP3 siRNA and qPCR. Lastly, we accessed the effect of decreased NLRP3 levels on ovariectomized (OVX) rats. To specifically deliver NLRP3 siRNA to osteoblasts, we constructed NLRP3 siRNA wrapping osteoblast-specific aptamer (CH6)-functionalized lipid nanoparticles (termed as CH6-LNPs-siNLRP3). Results: We found that the levels of NLRP3 inflammasome were significantly increased in patients with PMOP, and were negatively correlated with estradiol levels. NLRP3 knock-down influenced signal pathways including immune system process, interferon signal pathway. Notably, of the top ten up-regulated genes in NLRP3-reduced osteoblasts, nine genes (except Mx2) were enriched in immune system process, and five genes were related to interferon signal pathway. The in vitro results showed that CH6-LNPs-siNLRP3 was relatively uniform with a dimeter of 96.64 ± 16.83 nm and zeta potential of 38.37 ± 1.86 mV. CH6-LNPs-siNLRP3 did not show obvious cytotoxicity and selectively delivered siRNA to bone tissue. Moreover, CH6-LNPs-siNLRP3 stimulated osteoblast differentiation by activating ALP and enhancing osteoblast matrix mineralization. When administrated to OVX rats, CH6-LNPs-siNLRP3 promoted bone formation and bone mass, improved bone microarchitecture and mechanical properties by decreasing the levels of NLRP3, IL-1ß and IL-18 and increasing the levels of OCN and Runx2. Conclusion: NLRP3 inflammasome may be a new biomarker for PMOP diagnosis and plays a key role in the pathology of PMOP. CH6-LNPs-siNLRP3 has potential application for the treatment of PMOP.

Long-term grassland diversity-productivity relationship regulated by management regimes in northern China.

Grasslands are the most extensively distributed terrestrial ecosystems on Earth, providing a range of ecosystem services that are vital for sustaining human life and critical for sustainable development at the global scale. However, the relationship between the two most important attributes of grassland, plant diversity, and productivity, remains controversial even after many years of research. Here, we develop an analysis of covariance (ANCOVA) model based on decadal-scale experimental data from a degraded meadow steppe in northeastern Inner Mongolia, China to quantify the response of aboveground biomass (AGB) to plant species diversity under varying management regimes. We report that AGB responds negatively to the plant diversity in fallow grasslands and positively in grazing grasslands, transiting from negative to positive in mowing grasslands as mowing became more frequent. We show that the changing diversity-productivity relationships are driven by changes in species composition of the plant community, given the significant productivity gap between rare and non-rare species. This highlights the role of management in regulating the diversity-productivity relationships in grasslands. These results not only provide provocative insights into the relationships between plant diversity and productivity but also support more sustainable use and management of grassland resources.

Ultrasound wavelet spectra enable direct tissue recognition and full-color visualization.

Traditional brightness-mode ultrasound imaging is primarily constrained by the low specificity among tissues and the inconsistency among sonographers. The major cause is the imaging method that represents the amplitude of echoes as brightness and ignores other detailed information, leaving sonographers to interpret based on organ contours that depend highly on specific imaging planes. Other ultrasound imaging modalities, color Doppler imaging or shear wave elastography, overlay motion or stiffness information to brightness-mode images. However, tissue-specific scattering properties and spectral patterns remain unknown in ultrasound imaging. Here we demonstrate that the distribution (size and average distance) of scattering particles leads to characteristic wavelet spectral patterns, which enables tissue recognition and high-contrast ultrasound imaging. Ultrasonic wavelet spectra from similar particle distributions tend to cluster in the eigenspace according to principal component analysis, whereas those with different distributions tend to be distinguishable from one another. For each distribution, a few wavelet spectra are unique and act as a fingerprint to recognize the corresponding tissue. Illumination of specific tissues and organs with designated colors according to the recognition results yields high-contrast ultrasound imaging. The fully-colorized tissue-specific ultrasound imaging potentially simplifies the interpretation and promotes consistency among sonographers, or even enables the applicability for non-professionals.

Heterostructured MnSe/FeSe nanorods encapsulated by carbon with enhanced Na+ diffusion as anode materials for sodium-ion batteries.

The natural abundance of sodium has fostered the development of sodium-ion batteries for large-scale energy storage. However, the low capacity of the anodes hinders their future application. Herein, carbon-encapsulated MnSe-FeSe nanorods (MnSe-FeSe@C) have been fabricated by the in-situ transformation from polydopamine-coated MnO(OH)-Fe2O3. The heterostructure constructed by MnSe and FeSe nanocrystals induces the formation of built-in electric fields, accelerating electron transfer and ion diffusion, thereby improving reaction kinetics. In addition, carbon enclosure can buffer the volumetric stress and enhance the electrical conductivity. These aspects cooperatively endow the anode with superior cycling stability and distinguished rate performance. Specifically, the discharge capacity of MnSe-FeSe@C reaches 414.3 mA h g-1 at 0.1 A g-1 and 388.8 mA h g-1 even at a high current density of 5.0 A g-1. In addition, it still retains a high reversible capacity of 449.2 mA h g-1 after 700 long cycles at 1.0 A g-1. Further, the ab initio calculation has been employed to authenticate the existence of the built-in electric field by Bader charge, indicating that 0.24 electrons in MnSe were transferred to FeSe. The in-situ XRD has been used to evaluate the phase transition during the charging/discharging process, revealing the sodium ion storage mechanism. The construction of heterostructure material paves a new way to design performance-enhanced anode materials for sodium-ion batteries.

Causal relationship between sleep disorders and the risk of Alzheimer's disease: A Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Epidemiological studies have shown that sleep disorders are risk factors for Alzheimer's disease (AD), but the causal relationship between sleep disorders and AD risk is unknown. We aim to assess the potential genetic causal association between sleep characteristics and AD, which may contribute to early identification and prediction of risk factors for AD. METHODS: Seven sleep-related traits and the outcome phenotype AD were selected from published genome-wide association studies (GWASs). These sleep-related characteristics and instrumental variables (IVs) for AD were extracted. Two-sample and multivariate Mendelian randomization (MR) analyses were performed to assess the causal relationships between sleep characteristics and AD. The inverse variance weighted (IVW), weighted median (WME), weighted mode (WM), MR-Egger regression (MR-Egger) and simple mode (SM) models were used to evaluate causality. The existence of pleiotropy was detected and corrected by MR-Egger regression, MR pleiotropy residuals and outliers. RESULTS: A two-sample MR study revealed a positive causal association between sleep duration and the onset of AD (OR = 1.002, 95 % CI: 1.000-1.004), and the risk of AD increased with increasing sleep duration. The MR-Egger regression method and MR-PRESSO were used to identify and correct pleiotropy, indicating that there was no horizontal pleiotropy. Heterogeneity was evaluated by Cochran's Q, which indicated no heterogeneity. In a multivariate MR study with seven sleep characteristics corrected for each other, we found that sleep duration remained causally associated with AD (OR = 1.004, 95 % CI: 1.000-1.007). Moreover, we found that after mutual correction, daytime napping had a causal relationship with the onset of AD, and daytime napping may reduce the risk of AD (OR = 0.995, 95 % CI: 0.991-1.000). CONCLUSION: This study is helpful for the early identification and prediction of risk factors for AD, long sleep durations are a risk factor for AD, and daytime napping can reduce the risk of AD.

SCARB2 associates with tumor-infiltrating neutrophils and predicts poor prognosis in breast cancer.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in various aspects of breast cancer development and metastasis. Nevertheless, the expression, prognostic significance, and correlation with clinical features of SCARB2 in breast cancer, as well as the infiltrative characteristics of TME, remain largely unknown. METHODS: We analyzed the differential presentation of SCARB2 mRNA in breast cancer tissues and nontumorous breast tissues and prognosis by The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Additionally, the Tumor Immunity Estimation Resource (TIMER) was taken to evaluate the correlation between SCARB2 mRNA presence and tumor-infiltrating immune cells and immune checkpoints in the TME in breast cancer. We performed multiple immunohistochemical staining to verify the SCARB2 protein expression in breast cancer tissues and its relationship to immune cells and checkpoints and clinicopathological features. RESULTS: We identified elevated SCARB2 expression in breast cancer tissues, and high SCARB2 protein presentation was associated with advanced clinical stage and unfavorable prognosis. In addition, enhanced SCARB2 protein presence was closely correlated with up-regulation CD66b+ neutrophils infiltration in tumor tissues (r = 0.210, P < 0.05) and CD68 + CD163+ M2 macrophages in the interstitium (r = 0.233, P < 0.05), as well as the immune checkpoints, including PD-1 (r = 0.314, P < 0.01) protein expression. CONCLUSION: SCARB2 holds promise for predicting the clinical outcome of breast cancer patients and could serve as a potential therapeutic target.

Deprivation of methionine inhibits osteosarcoma growth and metastasis via C1orf112-mediated regulation of mitochondrial functions.

Osteosarcoma is a malignant bone tumor that primarily inflicts the youth. It often metastasizes to the lungs after chemotherapy failure, which eventually shortens patients' lives. Thus, there is a dire clinical need to develop a novel therapy to tackle osteosarcoma metastasis. Methionine dependence is a special metabolic characteristic of most malignant tumor cells that may offer a target pathway for such therapy. Herein, we demonstrated that methionine deficiency restricted the growth and metastasis of cultured human osteosarcoma cells. A genetically engineered Salmonella, SGN1, capable of overexpressing an L-methioninase and hydrolyzing methionine led to significant reduction of methionine and S-adenosyl-methionine (SAM) specifically in tumor tissues, drastically restricted the growth and metastasis in subcutaneous xenograft, orthotopic, and tail vein-injected metastatic models, and prolonged the survival of the model animals. SGN1 also sharply suppressed the growth of patient-derived organoid and xenograft. Methionine restriction in the osteosarcoma cells initiated severe mitochondrial dysfunction, as evident in the dysregulated gene expression of respiratory chains, increased mitochondrial ROS generation, reduced ATP production, decreased basal and maximum respiration, and damaged mitochondrial membrane potential. Transcriptomic and molecular analysis revealed the reduction of C1orf112 expression as a primary mechanism underlies methionine deprivation-initiated suppression on the growth and metastasis as well as mitochondrial functions. Collectively, our findings unraveled a molecular linkage between methionine restriction, mitochondrial function, and osteosarcoma growth and metastasis. A pharmacological agent, such as SGN1, that can achieve tumor specific deprivation of methionine may represent a promising modality against the metastasis of osteosarcoma and potentially other types of sarcomas as well.

Short-chain fatty acids: bridges between diet, gut microbiota, and health.

In recent years, gut microbiota has become a hot topic in the fields of medicine and life sciences. Short-chain fatty acids (SCFAs), the main metabolites of gut microbiota produced by microbial fermentation of dietary fiber, play a vital role in healthy and ill hosts. SCFAs regulate the process of metabolism, immune, and inflammation and have therapeutic effects on gastrointestinal and neurological disorders, as well as antitumor properties. This review summarized the production, distribution, and molecular mechanism of SCFAs, as well as their mechanisms of action in healthy and ill hosts. In addition, we also emphasized the negative effects of SCFAs, aiming to provide the public with a more comprehensive understanding of SCFAs.

Clinical application of serum tumor abnormal protein in prostate cancer patients.

PURPOSE: To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer. METHODS: This study enrolled a total of 265 patients who underwent prostate biopsy procedures from December 2017. TAP levels were assayed in their blood samples using a validated TAP testing kit. Comprehensive pathological assessments, including Gleason scores, TNM staging, and AJCC prognosis stages, were conducted on prostate cancer patients. Further analysis was carried out to examine the correlation between TAP expression levels and various clinical characteristics. RESULTS: A significantly elevated TAP concentration was discerned in prostate cancer patients relative to those with benign prostate hyperplasia. Moreover, a significantly elevated TAP expression was detected in prostate cancer patients with high Gleason score (≥ 8) and advanced stages (III and IV), as compared to those with Gleason scores of 6 and 7 and lower stages (I and II). When diagnosing prostate cancer in gray area of PSA, TAP demonstrated superior diagnostic capabilities over PSA alone, with higher diagnostic sensitivity, specificity and accuracy than fPSA/tPSA ratio. Additionally, post-surgical or hormonal treatment, there was a marked reduction in TAP expression level among prostate cancer patients. CONCLUSION: The assessment of TAP presents itself as a promising tool for early diagnosis and holds potential for sensitivity in monitoring treatment reponse in prostate cancer patients.

Machine learning model for predicting stroke recurrence in adult stroke patients with moyamoya disease and factors of stroke recurrence.

OBJECT: The aim of this study was at building an effective machine learning model to contribute to the prediction of stroke recurrence in adult stroke patients subjected to moyamoya disease (MMD), while at analyzing the factors for stroke recurrence. METHODS: The data of this retrospective study originated from the database of JiangXi Province Medical Big Data Engineering & Technology Research Center. Moreover, the information of MMD patients admitted to the second affiliated hospital of Nanchang university from January 1st, 2007 to December 31st, 2019 was acquired. A total of 661 patients from January 1st, 2007 to February 28th, 2017 were covered in the training set, while the external validation set comprised 284 patients that fell into a scope from March 1st, 2017 to December 31st, 2019. First, the information regarding all the subjects was compared between the training set and the external validation set. The key influencing variables were screened out using the Lasso Regression Algorithm. Furthermore, the models for predicting stroke recurrence in 1, 2, and 3 years after the initial stroke were built based on five different machine learning algorithms, and all models were externally validated and then compared. Lastly, the CatBoost model with the optimal performance was explained using the SHapley Additive exPlanations (SHAP) interpretation model. RESULT: In general, 945 patients suffering from MMD were recruited, and the recurrence rate of acute stroke in 1, 2, and 3 years after the initial stroke reached 11.43%(108/945), 18.94%(179/945), and 23.17%(219/945), respectively. The CatBoost models exhibited the optimal prediction performance among all models; the area under the curve (AUC) of these models for predicting stroke recurrence in 1, 2, and 3 years was determined as 0.794 (0.787, 0.801), 0.813 (0.807, 0.818), and 0.789 (0.783, 0.795), respectively. As indicated by the results of the SHAP interpretation model, the high Suzuki stage, young adults (aged 18-44), no surgical treatment, and the presence of an aneurysm were likely to show significant correlations with the recurrence of stroke in adult stroke patients subjected to MMD. CONCLUSION: In adult stroke patients suffering from MMD, the CatBoost model was confirmed to be effective in stroke recurrence prediction, yielding accurate and reliable prediction outcomes. High Suzuki stage, young adults (aged 18-44 years), no surgical treatment, and the presence of an aneurysm are likely to be significantly correlated with the recurrence of stroke in adult stroke patients subjected to MMD.

Analysis of Risk Factors for Pulmonary Infections During Radiotherapy in Lung Cancer Patients.

Objective: To investigate the risk factors for lung infection in lung cancer patients undergoing radiotherapy. Methods: We selected 142 patients with lung cancer who underwent radiotherapy at our hospital from January 2020 to June 2021. The patients were divided into groups according to whether they had pulmonary infection during radiotherapy in our hospital, which was infected group (n=44) and the uninfected group (n=98), respectively. To observe the incidence of lung infection in lung cancer patients during radiotherapy. The distribution of pathogenic bacteria in patients with pulmonary infection was observed. Clinical data of the two groups were collected and compared. The risk factors of lung cancer patients complicated with lung infection were analyzed by binary Logistic regression. Results: All patients with lung cancer complicated with lung infection underwent relevant examination, and the results showed that they were all complicated infections, and the composition ratio of Klebsiella pneumoniae was the highest (31.82%), followed by Staphylococcus, Pseudomonas, and fungi, which accounted for 27.27%, 22.73%, and 18.18%, respectively. Binary Logistic regression analysis showed that age ≥60 years old, smoking history ≥30 years, radiotherapy duration of combined drug regimen > 2 weeks, pathogenic bacteria combined infection, albumin content < 30 g/L were risk factors for lung cancer patients during radiotherapy. Conclusion: Age ≥60 years old, smoking history ≥30 years old, radiotherapy duration of combined drug regimen > 2 weeks, pathogenic bacteria combined infection, albumin content < 30 g/L are the risk factors for lung cancer patients during radiotherapy. Clinical prevention and intervention should be based on the aforementioned independent risk factors to decrease the incidence of lung infections, thereby enhancing patient prognosis.

Red Fluorescent Molecule with Aggregation-Induced Emission Based on Dehydroabietic Acid Diarylamine for Bioimaging.

In this paper, molecules with AIE red light properties were designed by coupling dehydroabietic acid diarylamine and 2,3-diphenylfumaronitrile, which were designated 2DTPA-CN and 2TPA-CN. The emission wavelengths were 683 nm and 701 nm, respectively. The 2DTPA-CN and 2TPA-CN showed typical AIE characteristics with large Stokes shifts of 7.4 × 104 cm-1 and 6.7 × 104 cm-1, respectively. The obvious solvatochromism and electron cloud distributions of HOMO/LUMO in the ground and excited states both reveal the intramolecular charge transfer (ICT) effect. The 2DTPA-CN, boasting exceptional biocompatibility, was successfully prepared into nanoparticles (NPs), which were applied to tumor cell imaging, showing good bioimaging effects both in vitro imaging in live cells and in vivo imaging in live mice. The results demonstrated that it possesses significant potential as an effective bioimaging reagent for the detection of tumor cells. Furthermore, the incorporation of 2,3-diphenylfumaronitrile moieties to dehydroabietic acid diarylamine emerged as a proficient approach to broaden the emission wavelengths of rosin-based fluorescent materials.

Schottky barrier reduction on optoelectronic responses in heavy ion irradiated WSe2 memtransistors.

Two-dimensional transition metal dichalcogenide-based memtransistors provide simulation, sensing, and storage capabilities for applications in a remotely operated aerospace environment. Swift heavy ion (SHI) irradiation technology is a common method to simulate the influences of radiation ions on electronic devices in space environments. Here, SHI irradiation technology under different conditions was utilized to produce complex defects in WSe2-based memtransistors. Low-resistance state to low-resistance state (LRS-LRS) switching behaviors under light illumination were achieved and photocurrent responses with different spike trains were observed in SHI-irradiated memtransistors, which facilitated the design of devices with enriched analog functions. Reduction of the Schottky barrier height due to the introduced defects at the metal/WSe2 interface was confirmed to be the major factor responsible for the observed behaviors. 1T phase and concentric circle-type vacancies were also created in the SHI-irradiated 2H-WSe2 channel besides the amorphous structure; these complex defects could seriously affect the transport properties of the devices. We believe that this work serves as a foundation for aerospace radiation applications of all-in-one devices. It also opens a new application field of heavy ion irradiation technology for the development of multiterminal memtransistor-based optoelectronic artificial synapses for neuromorphic computing.

Bushen Huoxue recipe ameliorates ovarian function via promoting BMSCs proliferation and homing to ovaries in POI mice.

BACKGROUND: Premature ovarian insufficiency (POI) is a tricky puzzle in the field of female reproductive medicine. Bushen Huoxue recipe (BHR), a traditional Chinese medicine compound based on the combination of kidney-tonifying and blood-activating functions, has shown excellent efficacy in improving female irregular menstruation, POI, and infertility. However, the potential mechanism of BHR in POI treatment has not yet been elucidated. Bone marrow mesenchymal stem cells (BMSCs), a type of pluripotent stem cells, have received increasing attention for their significant role in improving ovarian function and restoring fertility in women with POI. PURPOSE: This study aimed to evaluate the therapeutic effect of BHR in POI mice and explore its potential mechanism. METHODS: A POI mouse model was established with a single intraperitoneal injection of 120 mg/kg cyclophosphamide (CTX). Distilled water, BHR, or dehydroepiandrosterone was administered via gavage for 28 consecutive days. The effect of BHR on ovarian function in POI mice was evaluated by assessing the estrous cycle, ovarian morphology, follicular development, hormone levels, and angiogenesis. The proportion of BMSCs in bone marrow, peripheral blood, and ovary was analyzed via flow cytometry, and the level of molecules mediating migration and homing in ovary was measured. Cell viability assays, scratch healing assays and transwell migration assays were performed to explore the effect of BHR on BMSCs proliferation and migration in vitro, and its potential mechanism was explored. RESULTS: BHR significantly ameliorated estrous cycle disorders, hormone disorders, ovarian morphology, ovarian microvascular formation, and ovarian reserve in POI mice. Meanwhile, the number of BMSCs number in the bone marrow, peripheral blood, and ovary was apparently increased. Of note, BHR increased the level of hepatocyte growth factor (HGF)/cellular mesenchymal epithelial transition factor (cMET) and stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor 4 (CXCR4) in the ovaries of POI mice. Moreover, BHR treatment promoted BMSCs proliferation and migration in vitro, with a significant increase in the level of proliferating cell nuclear antigen, cMET, and CXCR4. CONCLUSIONS: BHR effectively restored ovarian reserve, ovarian function, and ovarian angiogenesis in CTX-induced POI mice. In addition, BHR promoted BMSCs proliferation, migration, and homing to the ovary, which was mediated by the SDF-1/CXCR4 and HGF/cMET signaling axis. Finally, the amelioration of ovarian reserve and ovarian function in CTX-induced POI mice by BHR may be related to its promotion of endogenous BMSCs proliferation and homing.