The genetic spectrum of NF1 variants in 10 unrelated Chinese families with neurofibromatosis type 1.

OBJECTIVES: To investigate the clinical and genetic features in a cohort of Chinese families with neurofibromatosis type 1 (NF1). METHODS: The clinical information of 21 patients with NF1 in 10 families was retrospectively analyzed. To broaden the genetic spectrum of NF1, multiplex ligation-dependent probe amplification analysis was performed first, followed by the whole-exome sequencing, in order to identify pathogenic or potentially pathogenic variants of NF1 gene in 10 unrelated Chinese families. RESULTS: Nine different NF1 variants were identified in all 10 families. Of these, 7 were known pathogenic variants and included the exon 1 deletion, exons 1-58 deletion, c.5401C>T (p.Q1801*), c.2291-2A>C, c.484C>T (p.Q162*), c.4922G>A (p.W1641*) and c.1019_1020del (p.S340Cfs*25). The 2 novel variants were c.5197T>C (p.S1733P) and c.783_797delinsC (p.K261Nfs*25). The p.S1733P variant was classified as a variant of uncertain significance, while p.K261Nfs*25 was classified as pathogenic. Hence, the positive detection rate of NF1 variants was 100% (10/10). While the truncating variants were responsible for 60.0% (6/10) of the cases, the splicing variant was responsible for 10% (1/10) of the cases. CONCLUSION: We identified 2 novel heterozygous variants (c.5197T>C and c.783_797delinsC) in the NF1 gene, which broadens the genetic spectrum of the NF1 gene.

Low-dose pegylated recombinant human granulocyte-colony stimulating factor as hematopoietic support for adjuvant chemotherapy in Chinese patients with breast cancer: An open-label, randomized, non-inferiority trial.

AIMS: The recommended dosage of pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) for Western chemotherapy patients is 6 mg per cycle. However, for Eastern Asians, the optimal dose remains unknown. METHODS: This open-label, randomized, non-inferiority trial (NCT05283616) enrolled Chinese female breast cancer patients receiving adjuvant chemotherapy. Participants were randomized to receive either 3 or 6 mg of PEG-rhG-CSF per cycle, stratified by body weight (BW; ≤60 kg vs. >60 kg). The primary endpoint was timely absolute neutrophil count (ANC) recovery before the second cycle of chemotherapy. RESULTS: A total of 122 patients were randomized and 116 were included for efficacy analyses. The timely ANC recovery rate in the 3 mg arm was 89.8%, compared to 93.0% in the 6 mg arm (one-sided 95% confidence interval [CI] lower limit for difference: -11.7%), meeting the prespecified non-inferiority margin of 15%. The rate was 93.3% with PEG-rhG-CSF 3 mg and 96.6% with 6 mg in patients with BW ≤ 60 kg, and 86.2% and 89.3%, respectively, in those with BW > 60 kg. Although the incidence of severe neutropenia was similar across arms, the occurrence of excessively high ANC and white blood cell counts was higher in the 6 mg arm. No grade ≥3 adverse events related to PEG-rhG-CSF occurred. CONCLUSION: Three milligrams of PEG-rhG-CSF per cycle provided non-inferior neutrophil protection and attenuated neutrophil overshoot compared to 6 mg doses. This low-dose regimen could be a new supportive care option for Chinese breast cancer patients receiving anthracycline-based adjuvant chemotherapy.

Elevated lead mobility in sediments of a eutrophic drinking water reservoir during spring and summer seasons: Insights from isotopic signatures.

Lead (Pb) pollution in sediments remains a major concern for ecosystem quality due to the robust interaction at the sediment/water interface, particularly in shallow lakes. However, understanding the mechanism behind seasonal fluctuations in Pb mobility in these sediments is lacking. Here, the seasonal variability of Pb concentration and isotopic ratio were investigated in the uppermost sediments of a shallow eutrophic drinking lake located in southeast China. Results reveal a sharp increase in labile Pb concentration during autumn-winter period, reaching ∼ 3-fold higher levels than during the spring-summer seasons. Despite these fluctuations, there was a notable overlap in the Pb isotopic signatures within the labile fraction across four seasons, suggesting that anthropogenic sources are not responsible for the elevated labile Pb concentration in autumn-winter seasons. Instead, the abnormally elevated labile Pb concentration during autumn-winter was probably related to reduction dissolution of Fe/Mn oxides, while declined labile Pb concentration during spring-summer may be attributed to adsorption/precipitation of Fe/Mn oxides. These large seasonal changes imply the importance of considering seasonal effects when conducting sediment sampling. We further propose a solution that using Pb isotopic signatures within the labile fraction instead of the bulk sediment can better reflect the information of anthropogenic Pb sources.

Chlorophyll a acts as a natural photosensitizer to drive nitrate reduction in nonphotosynthetic microorganisms.

With the death and decomposition of widely distributed photosynthetic organisms, free natural pigments are often detected in surface water, sediment and soil. Whether free pigments can act as photosensitizers to drive biophotoelectrochemical metabolism in nonphotosynthetic microorganisms has not been reported. In this work, we provide direct evidence for the photoelectrophic relationship between extracellular chlorophyll a (Chl a) and nonphotosynthetic microorganisms. The results show that 10 µg of Chl a can produce significant photoelectrons (∼0.34 A/cm2) upon irradiation to drive nitrate reduction in Shewanella oneidensis. Chl a undergoes structural changes during the photoelectric process, thus the ability of Chl a to generate a photocurrent decreases gradually with increasing illumination time. These changes are greater in the presence of microorganisms than in the absence of microorganisms. Photoelectron transport from Chl a to S. oneidensis occurs through a direct pathway involving the cytochromes MtrA, MtrB, MtrC and CymA but not through an indirect pathway involving riboflavin. These findings reveal a novel photoelectrotrophic linkage between natural photosynthetic pigments and nonphototrophic microorganisms, which has important implications for the biogeochemical cycle of nitrogen in various natural environments where Chl a is distributed.

Real-time quantitative detection of hydrocolloid adulteration in meat based on Swin Transformer and smartphone.

Hydrocolloids are widely used in meat products as common food additives. However, research has indicated that excessive consumption of these hydrocolloids may have potential health implications. Currently, consumers mainly rely on sensory evaluation to identify hydrocolloid adulteration in meat products. Although many studies on quantitative detection of hydrocolloids have been conducted by biochemical methods in laboratory environments, there is currently a lack of effective tools for consumers and regulators to obtain real-time and reliable information on hydrocolloid adulteration. To address this challenge, a smartphone-based computer vision method was developed to quantitatively detect carrageenan adulteration in beef in this work. Specifically, Swin Transformer models, along with pre-training and fine-tuning techniques, were used to successfully automate the classification of beef into nine different levels of carrageenan adulteration, ranging from 0% to 20%. Among the tested models, Swin-Tiny (Swin-T) achieved the highest trade-off performance, with a Top-1 accuracy of 0.997, a detection speed of 3.2 ms, and a model size of 103.45 Mb. Compared to computer vision, the electrochemical impedance spectroscopy achieved a lower accuracy of 0.792 and required a constant temperature environment and a waiting time of around 30 min for data stabilization. In addition, Swin-T model was also capable of distinguishing between different types of hydrocolloids with a Top-1 accuracy of 0.975. This study provides consumers and regulators with a valuable tool to obtain real-time quantitative information about meat adulteration anytime, anywhere. PRACTICAL APPLICATION: This research provides a practical solution for regulators and consumers to non-destructively and quantitatively detect the content and type of hydrocolloids in beef in real-time using smartphones. This innovation has the potential to significantly reduce the costs associated with meat quality testing, such as the use of chemical reagents and expensive instruments.

Juvenile hormone signal transducer hairy inhibits Krüppel homolog1 expression.

Hairy and Krüppel homolog 1 (Kr-h1) are transcriptional repressors that act synergistically to mediate the gene-repressive action of juvenile hormone (JH). However, whether a regulatory relationship exists between Hairy and Kr-h1 remains unclear. In this study, an inhibitory effect of Hairy on Kr-h1 expression was found. Genetic studies in Drosophila have shown that the simultaneous overexpression of Hairy and Kr-h1 can rescue the defective phenotypes caused by the overexpression of a single factor. Reduced expression of Kr-h1 was observed in Hairy-overexpressing flies and cells, whereas the expression levels of Hairy were unaffected in cells with ectopic expression of Kr-h1. The inhibitory effect of Hairy on Kr-h1 expression was found to occur at the transcriptional level, as Hairy bound directly to the B-box within the Kr-h1 promoter via the bHLH motif and recruited the corepressors C-terminal binding protein (CtBP) and Groucho (Gro) through the PLSLV and WRPW motifs, respectively. Our findings revealed a regulatory relationship between two JH response factors, which advances our understanding of the molecular mechanism of JH signaling.

Improved U-net network asphalt pavement crack detection method.

Road crack detection is one of the important parts of road safety detection. Aiming at the problems such as weak segmentation effect of basic U-Net on pavement crack, insufficient precision of crack contour segmentation, difficult to identify narrow crack and low segmentation accuracy, this paper proposes an improved U-net network pavement crack segmentation method. VGG16 and Up_Conv (Upsampling Convolution) modules are introduced as backbone network and feature enhancement network respectively, and the more abstract features in the image are extracted by using the Block depth separable convolution blocks, and the multi-scale features are captured and enhanced by higher level semantic information to improve the recognition accuracy of narrow cracks in the road surface. The improved network embedded the Ca(Channel Attention) attention mechanism in U-net's jump connection to enhance the crack portion to suppress background noise. At the same time, DG_Conv(Depthwise GSConv Convolution) module and UnetUp(Unet Upsampling) module are added in the decoding part to extract richer features through more convolutional layers in the network, so that the model pays more attention to the detailed part of the crack, so the segmentation accuracy can be improved. In order to verify the model's ability to detect cracks in complex backgrounds, experiments were carried out on CFD and Deepcrack datasets. The experimental results show that compared with the traditional U-net network F1-score and mIoU have increased by 13.6% and 9.9% respectively. Superior to advanced models such as U-net, Segnet and Linknet in accuracy and generalization ability, the improved model provides a new method for asphalt pavement crack detection. The model is more conducive to practical application and ground deployment, and can be applied in road maintenance projects.

Sex-specific association of serum dehydroepiandrosterone and its sulfate levels with osteoporosis in type 2 diabetes.

INTRODUCTION: This study is to investigate the relation between serum dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) levels and the risk of osteoporosis in patients with T2DM. MATERIALS AND METHODS: This cross-sectional study involved 938 hospitalized patients with T2DM. Linear regression models were used to explore the relationship between DHEA and DHEAS and the BMD at different skeletal sites. Multinominal logistic regression models and the restricted cubic spline (RCS) were used to evaluate the associations of DHEA and DHEAS with the risks of osteopenia and/or osteoporosis. RESULTS: In postmenopausal women with T2DM, after adjustment for confounders including testosterone and estradiol, DHEA showed a significant positive correlation with lumbar spine BMD (P = 0.013). Moreover, DHEAS exhibited significant positive correlations with BMD at three skeletal sites: including femoral neck, total hip, and lumbar spine (all P < 0.05). Low DHEA and DHEAS levels were associated with increased risk of osteopenia and/or osteoporosis (all P < 0.05) and the risk of osteoporosis gradually decreased with increasing DHEAS levels (P overall = 0.018, P-nonlinear = 0.559). However, DHEA and DHEAS levels in men over the age of 50 with T2DM were not associated with any of above outcomes. CONCLUSION: In patients with T2DM, independent of testosterone and estradiol, higher DHEA and DHEAS levels are associated with higher BMD and lower risk of osteopenia/osteoporosis in postmenopausal women but not men over the age of 50.

The association between blood pressure variability and renal damage in patients with primary aldosteronism.

This research examines the association between blood pressure variability (BPV) and renal damage in a cohort of 129 primary aldosteronism (PA) patients, employing ambulatory blood pressure monitoring (ABPM) for comparative analysis with individuals diagnosed with essential hypertension (EH). The study reveals that PA patients exhibited significantly elevated levels of cystatin C and urine microalbumin/creatinine ratio (UACR). Additionally, a higher prevalence of non-dipping blood pressure patterns in PA patients suggests an increased risk of circadian blood pressure regulation disturbances. Notably, while most BPV indices were comparable between the two groups, the standard deviation of 24-h weighted diastolic blood pressure was markedly lower in the PA cohort, distinguishing it as a unique variable. Through multiple linear regression analysis, the duration of hypertension, angiotensin II concentrations, and daytime systolic blood pressure standard deviation emerged as significant determinants of estimated glomerular filtration rate (eGFR) in PA patients. Furthermore, UACR was significantly influenced by variables including the 24-h weighted standard deviation (wSD) of systolic BP, glycosylated hemoglobin levels, nocturnal systolic BP peaks, aldosterone-renin ratio (ARR), and total cholesterol, with the most pronounced association observed with the 24-h wSD of systolic BP (ß = 0.383).The study also found significant correlations between the 24-h wSD of systolic BP, ARR, HbA1c, serum potassium levels, and 24-h urinary microalbumin, underscoring the critical role of the 24-h wSD of systolic BP (ß = 0.267). These findings underscore the imperative of an integrated management strategy for PA, addressing the intricate interconnections among metabolic abnormalities, blood pressure variability, and renal health outcomes.

Longitudinal change of serum exosomal miR-186-5p estimates major adverse cardiac events in acute myocardial infarction patients receiving percutaneous coronary intervention.

Objective: Our recently published study discovers that exosomal microRNA (miR)-186-5p promotes vascular smooth muscle cell viability and invasion to facilitate atherosclerosis. This research aimed to explore the prognostic implication of serum exosomal miR-186-5p in acute myocardial infarction (AMI) patients receiving percutaneous coronary intervention (PCI). Methods: One hundred and fifty AMI patients receiving PCI and 50 healthy controls (HCs) were screened. Serum exosomal miR-186-5p was detected by reverse transcriptase-quantitative polymerase chain reaction assay in AMI patients at admission and after PCI, as well as in HCs after enrollment. Major adverse cardiac events (MACE) were recorded during follow-up in AMI patients receiving PCI. Results: Serum exosomal miR-186-5p was raised in AMI patients vs. HCs (P < 0.001). Besides, serum exosomal miR-186-5p was positively linked to body mass index (P = 0.048), serum creatinine (P = 0.021), total cholesterol (P = 0.029), and C-reactive protein (P = 0.018); while it was reversely linked with estimated glomerular filtration rate (P = 0.023) in AMI patients. Interestingly, serum exosomal miR-186-5p was correlated with the diagnosis of ST-segment elevation myocardial infarction (P = 0.034). Notably, serum exosomal miR-186-5p was decreased after PCI vs. at admission (P < 0.001). The 6-, 12-, 18-, and 24-month accumulating MACE rates were 4.5%, 8.9%, 14.8%, and 14.8% in AMI patients. Furthermore, serum exosomal miR-186-5p ≥3.39 (maximum value in HCs) after PCI (P = 0.021) and its decrement percentage

Pure total flavonoids from Citrus ameliorate NSAIDs-induced intestinal mucosal injury via regulation of exosomal LncRNA H19 and protective autophagy.

Introduction: Non-steroid anti-inflammatory drugs (NSAIDs) are a class of prescription drugs with antipyretic, analgesic, anti-inflammatory, and antiplatelet effects. However, long-term use of NSAIDs will disrupt the intestinal mucosal barrier, causing erosion, ulcers, bleeding, and even perforation. Pure total flavonoids from Citrus (PTFC) is extracted from the dried peel of Citrus, showing a protective effect on intestinal mucosal barrier with unclear mechanisms. Methods: In the present study, we used diclofenac (7.5 mg kg-1, i.g.) to induce a rat model of NSAIDs-related intestinal lesions. PTFC (50, 75, 100 mg·kg-1 d-1, i.g.) was administered 9 days before the initial diclofenac administration, followed by co-administration on the last 5 days. Exosomes were identified by western blotting and transmission electron microscopy (TEM), and then co-cultured with IEC-6 cells. The expression of long non-coding RNA (lncRNA) H19, autophagy-related 5 (Atg5), ZO-1, Occludin, and Claudin-1 were detected by quantitative real-time PCR (qRT-PCR). The expression of light chain 3 (LC3)-I, LC3-II, ZO-1, Occludin and Claudin-1 proteins was tested by western blotting. The localization of both exosomes and autophagosomes was examined by immunofluorescent technique. Results: The treatment of PTFC attenuated intestinal mucosal mechanical barrier function disturbance in diclofenac-induced NSAIDs rats. IEC-6 cells co-cultured with NSAIDs rats-derived exosomes possessed the lowest levels of protective autophagy, and severe intestinal barrier injuries. Cells co-cultured with the exosomes extracted from rats administrated PTFC exhibited an improvement of autophagy and intestinal mucosal mechanical barrier function. The prevention effect was proportional to the concentration of PTFC administered. Conclusion: PTFC ameliorated NSAIDs-induced intestinal mucosal injury by down-regulating exosomal lncRNA H19 and promoting autophagy.

Research on Tire Surface Damage Detection Method Based on Image Processing.

The performance of the tire has a very important impact on the safe driving of the car, and in the actual use of the tire, due to complex road conditions or use conditions, it will inevitably cause immeasurable wear, scratches and other damage. In order to effectively detect the damage existing in the key parts of the tire, a tire surface damage detection method based on image processing was proposed. In this method, the image of tire side is captured by camera first. Then, the collected images are preprocessed by optimizing the multi-scale bilateral filtering algorithm to enhance the detailed information of the damaged area, and the optimization effect is obvious. Thirdly, the image segmentation based on clustering algorithm is carried out. Finally, the Harris corner detection method is used to capture the "salt and pepper" corner of the target region, and the segmsegmed binary image is screened and matched based on histogram correlation, and the target region is finally obtained. The experimental results show that the similarity detection is accurate, and the damage area can meet the requirements of accurate identification.

Berberine mitigates diclofenac-induced intestinal mucosal mechanical barrier dysfunction through the restoration of autophagy by inhibiting exosome-mediated lncRNA H19.

Small intestine damage caused by diclofenac is called diclofenac enteropathy. Berberine (BBR), a class of isoquinoline alkaloids derived from Berberis vulgaris and Phellodendron amurense, is widely used in intestinal diseases. The present study evaluated the protective effect of BBR on the intestinal mucosal mechanical barrier in diclofenac enteropathy and its possible action mechanism. The in vitro animal experiment revealed that BBR downregulated the expression of long non-coding RNA H19 (lncRNA H19) in the small intestine and exosomes. In the co-culture experiment involving exosomes and intestinal epithelial cell-6 (IEC-6) cells, the results of qRT-PCR, western blotting, and immunofluorescence assays demonstrated that the elevated expression of lncRNA H19 in the small intestine, conveyed via exosomes derived from the diclofenac group, suppressed the expression levels of autophagy-associated protein 5 (Atg 5) and light chain 3 (LC 3), as well as and the tight junction (TJ) proteins zonula occludens-1 (ZO-1), claudin-1, and occluding, relative to the control group. BBR treatment attenuated exosomal lncRNA H19 levels, upregulated the expression of Atg5 and LC3 expression, enhanced TJ protein expression, and increased the light chain 3 (LC3)-II/LC3-I ratio. These findings significantly elucidated that BBR promoted the restoration of autophagy in IECs by inhibiting exosomal lncRNA H19, thereby mitigating the impairment of the intestinal mucosal mechanical barrier function in diclofenac enteropathy. The process involving exosomal lncRNA H19 regulating autophagy, thereby affecting the intestinal mucosal mechanical barrier, offers a novel perspective for the application of BBR in the treatment of diclofenac enteropathy.

A machine learning-based model analysis for serum markers of liver fibrosis in chronic hepatitis B patients.

Early assessment and accurate staging of liver fibrosis may be of great help for clinical diagnosis and treatment in patients with chronic hepatitis B (CHB). We aimed to identify serum markers and construct a machine learning (ML) model to reliably predict the stage of fibrosis in CHB patients. The clinical data of 618 CHB patients between February 2017 and September 2021 from Zhejiang Provincial People's Hospital were retrospectively analyzed, and these data as a training cohort to build the model. Six ML models were constructed based on logistic regression, support vector machine, Bayes, K-nearest neighbor, decision tree (DT) and random forest by using the maximum relevance minimum redundancy (mRMR) and gradient boosting decision tree (GBDT) dimensionality reduction selected features on the training cohort. Then, the resampling method was used to select the optimal ML model. In addition, a total of 571 patients from another hospital were used as an external validation cohort to verify the performance of the model. The DT model constructed based on five serological biomarkers included HBV-DNA, platelet, thrombin time, international normalized ratio and albumin, with the area under curve (AUC) values of the DT model for assessment of liver fibrosis stages (F0-1, F2, F3 and F4) in the training cohort were 0.898, 0.891, 0.907 and 0.944, respectively. The AUC values of the DT model for assessment of liver fibrosis stages (F0-1, F2, F3 and F4) in the external validation cohort were 0.906, 0.876, 0.931 and 0.933, respectively. The simulated risk classification based on the cutoff value showed that the classification performance of the DT model in distinguishing hepatic fibrosis stages can be accurately matched with pathological diagnosis results. ML model of five serum markers allows for accurate diagnosis of hepatic fibrosis stages, and beneficial for the clinical monitoring and treatment of CHB patients.

Single-cell sequencing reveals the impact of endothelial cell PIEZO1 expression on thoracic aortic aneurysm.

INTRODUCTION: Thoracic aortic aneurysm (TAA) is a severe vascular disease that threatens human life, characterized by focal dilatation of the entire aortic wall, with a diameter 1.5 times larger than normal. PIEZO1, a mechanosensitive cationic channel, monitors mechanical stimulations in the environment, transduces mechanical signals into electrical signals, and converts them into biological signals to activate intracellular signaling pathways. However, the role of PIEZO1 in TAA is still unclear. METHODS: We analyzed a single-cell database to investigate the expression level of PIEZO1 in TAA. We constructed a conditional knockout mouse model of Piezo1 and used the PIEZO1 agonist Yoda1 to intervene in the TAA model mice established by co-administration of BAPN and ANG-II. Finally, we explored the effect of Yoda1 on TAA in vitro. RESULTS AND DISCUSSION: We observed decreased PIEZO1 expression in TAA at both RNA and protein levels. Single-cell sequencing identified a specific reduction in Piezo1 expression in endothelial cells. Administration of PIEZO1 agonist Yoda1 prevented the formation of TAA. In PIEZO1 endothelial cell conditional knockout mice, Yoda1 inhibited TAA formation by interfering with PIEZO1. In vivo and in vitro experiments demonstrated that the effect of Yoda1 on endothelial cells involved macrophage infiltration, extracellular matrix degradation, and neovascularization. This study highlights the role of PIEZO1 in TAA and its potential as a therapeutic target, providing opportunities for clinical translation.

DACH1 Attenuates Airway Inflammation in Chronic Obstructive Pulmonary Disease by Activating NRF2 Signaling.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways characterized by impaired lung function induced by cigarette smoke (CS). Reduced DACH1 (dachshund homolog 1) expression has a detrimental role in numerous disorders, but its role in COPD remains understudied. This study aimed to elucidate the role and underlying mechanism of DACH1 in airway inflammation in COPD by measuring DACH1 expression in lung tissues of patients with COPD. Airway epithelium-specific DACH1-knockdown mice and adenoassociated virus-transfected DACH1-overexpressing mice were used to investigate the role of DACH1 and the potential for therapeutic targeting in experimental COPD caused by CS. Furthermore, we discovered a potential mechanism of DACH1 in inflammation induced by CS extract stimulation in vitro. Compared with nonsmokers and smokers without COPD, patients with COPD had reduced DACH1 expression, especially in the airway epithelium. Airway epithelium-specific DACH1 knockdown aggravated airway inflammation and lung function decline caused by CS in mice, whereas DACH1 overexpression protected mice from airway inflammation and lung function decline. DACH1 knockdown and overexpression promoted and inhibited IL-6 and IL-8 secretion, respectively, in 16HBE human bronchial epidermal cells after CS extract stimulation. NRF2 (nuclear factor erythroid 2-related factor 2) was discovered to be a novel downstream target of DACH1, which binds directly to its promoter. By activating NRF2 signaling, DACH1 induction reduced inflammation. DACH1 levels are lower in smokers and nonsmoking patients with COPD than in nonsmokers. DACH1 has protective effects against inflammation induced by CS by activating the NRF2 signaling pathway. Targeting DACH1 is a potentially viable therapeutic approach for COPD treatment.

A Broadband Photodetector Based on Non-Layered MnS/WSe2 Type-I Heterojunctions with Ultrahigh Photoresponsivity and Fast Photoresponse.

The separation of photogenerated electron-hole pairs is crucial for the construction of high-performance and wide-band responsive photodetectors. The type-I heterojunction as a photodetector is seldomly studied due to its limited separation of the carriers and narrow optical response. In this work, we demonstrated that the high performance of type-I heterojunction as a broadband photodetector can be obtained by rational design of the band alignment and proper modulation from external electric field. The heterojunction device is fabricated by vertical stacking of non-layered MnS and WSe2 flakes. Its type-I band structure is confirmed by the first-principles calculations. The MnS/WSe2 heterojunction presents a wide optical detecting range spanning from 365 nm to 1550 nm. It exhibits the characteristics of bidirectional transportation, a current on/off ratio over 103, and an excellent photoresponsivity of 108 A W-1 in the visible range. Furthermore, the response time of the device is 19 ms (rise time) and 10 ms (fall time), which is much faster than that of its constituents MnS and WSe2. The facilitation of carrier accumulation caused by the interfacial band bending is thought to be critical to the photoresponse performance of the heterojunction. In addition, the device can operate in self-powered mode, indicating a photovoltaic effect.

Ncf1 knockout in SMCs exacerbates angiotensin II-induced aortic aneurysm and dissection by activating the STING pathway.

AIMS: Aortic aneurysm and dissection (AAD) is caused by the progressive loss of aortic smooth muscle cells (SMCs) and is associated with a high mortality rate. Identifying the mechanisms underlying SMC apoptosis is crucial for preventing AAD. Neutrophil cytoplasmic factor 1 (Ncf1) is essential in reactive oxygen species (ROS) production and SMC apoptosis; Ncf1 absence leads to autoimmune diseases and chronic inflammation. Here, the role of Ncf1 in angiotensin II (Ang II)-induced AAD was investigated. METHODS AND RESULTS: Ncf1 expression increased in injured SMCs. Bioinformatics analysis identified Ncf1 as a mediator of AAD-associated SMC damage. Ncf1 expression is positively correlated with DNA replication and repair in SMCs of AAD aortas. AAD incidence increased in Ang II-challenged Sm22CreNcf1fl mice. Transcriptomics showed that Ncf1 knockout activated the stimulator of interferon genes (STING) and cell death pathways. The effects of Ncf1 on SMC death and the STING pathway in vitro were examined. Ncf1 regulated the hydrogen peroxide-mediated activation of the STING pathway and inhibited SMC apoptosis. Mechanistically, Ncf1 knockout promoted the ubiquitination of nuclear factor erythroid 2-related factor 2 (NRF2), thereby inhibiting the negative regulatory effect of NRF2 on the stability of STING mRNA and ultimately promoting STING expression. Additionally, the pharmacological inhibition of STING activation prevented AAD progression. CONCLUSIONS: Ncf1 deficiency in SMCs exacerbated Ang II-induced AAD by promoting NRF2 ubiquitination and degradation and activating the STING pathway. These data suggest that Ncf1 may be a potential therapeutic target for AAD treatment.