Tenecteplase thrombolysis for stroke up to 24 hours after onset with perfusion imaging selection: the umbrella phase IIa CHABLIS-T randomised clinical trial.

BACKGROUND: The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/medium vessel occlusion beyond 4.5-hour time window. METHODS: The CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase was an investigator-initiated, umbrella phase IIa, open-label, blinded-endpoint, Simon's two-stage randomised clinical trial in 13 centres across mainland China. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5-24 hours from time of last seen well were randomised to receive 0.25 mg/kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5-10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24-48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis. RESULTS: A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon's two-stage design. DISCUSSION: Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5-24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04086147, https://clinicaltrials.gov/ct2/show/NCT04086147).

Metagenomic Next-Generation Sequencing Contributes to the Diagnosis of Pneumonia Caused by Chlamydia abortus in a Male Patient: Case Report and Literature Review.

Background: Chlamydia abortus is generally considered as the main cause of ruminants abortion, but it rarely causes human infection resulting in abortion or pneumonia. Case Presentation: We report a case of male patient with pneumonia caused by Chlamydia abortus. Results of next generation sequencing (NGS) in the bronchoalveolar lavage fluid (BALF) indicated Chlamydia abortus infection. The patient was treated with intravenous infusion of doxycycline. The clinical symptoms of this patient were ameliorated significantly, and all these improvement were indicated by laboratory parameters significantly. Shown as chest computed tomography (CT), most of the inflammation had been absorbed after doxycycline treatment. Conclusion: Chlamydia abortus mainly infects ruminants and occasionally humans. NGS has its own advantages of rapidity, sensitivity and specificity in detecting Chlamydia abortus. Doxycycline exhibits a great therapeutic effect on pneumonia caused by Chlamydia abortus.

The metabolic score for insulin resistance as a predictor of clinical outcome in stroke patients treated by intravenous thrombolysis.

BACKGROUND AND PURPOSE: Insulin resistance is associated with clinical outcomes among patients with ischemic stroke. We aimed to investigate the association between metabolic score for insulin resistance (METS-IR) and clinical outcomes in stroke patients treated by intravenous thrombolysis (IVT). METHODS: We recruited participants treated with IVT from a prospective registry including 3 stroke centers. Poor outcome was defined as a modified Rankin scale score ≥ 3 points at 90 days after the index stroke. We performed logistic regression models to investigate the association between METS-IR and the risk of poor outcome. We used the receiver operative characteristic to assess the discriminative ability and the restricted cubic spline to explore the relationship between METS-IR and the poor outcome. RESULTS: This study enrolled a total of 1074 patients (median age, 68; 63.8% male). Three hundred sixty (33.5%) patients had poor outcome after IVT. METS-IR was associated with the risk of the poor outcome with the increase of confounding factors in models (odds ratio [OR], 1.078; 95% confidence interval [CI], 1.058-1.099; P < 0.001). The area under the curve for METS-IR for predicting the poor outcome was 0.790 (95% CI, 0.761-0.819). The restricted cubic spline revealed an increasing and non-linear association between METS-IR and the poor outcome (P for non-linearity < 0.001). CONCLUSION: Our study found that METS-IR was associated with an increased risk of poor outcome after IVT. Further studies are warranted to investigate the efficacy of anti-diabetic agents regarding IR on clinical outcomes after IVT.

Converting Nafion into Li+ -Conductive Nanoporous Materials.

Sulfonated polymers have long been used as proton-conducting materials in fuel cells, and their ionic transport features are highly attractive for electrolytes in lithium-ion/metal batteries (LIBs/LMBs). However, most studies are still based on a preconceived notion of using them directly as polymeric ionic carriers, which precludes exploring them as nanoporous media to construct efficient lithium ions (Li+ ) transport network. Here, effective Li+ -conducting channels realized by swelling nanofibrous Nafion is demonstrated, which is a classical sulfonated polymer in fuel cells. The sulfonic acid groups, interact with LIBs liquid electrolytes to form porous ionic matrix of Nafion and assist partial desolvation of Li+ -solvates to further enhance Li+ transport. Li-symmetric cells and Li-metal full cells (Li4 Ti5 O12 or high-voltage LiNi0.6 Co0.2 Mn0.2 O2 as a cathode) with such membrane show excellent cycling performance and stabilized Li-metal anode. The finding provides a strategy to convert the vast sulfonated polymer family into efficient Li+ electrolyte, promoting the development of high-energy-density LMBs.

Antioxidant mechanism of a continuous microenvironment regulation system for prolonging the shelf-life of red grapes.

Red grapes (Vitis vinifera L.) have a high sugar content, thin skins, and relatively short shelf-life after harvesting. We developed polylactic acid/polybutylene succinate film, prepared by extrusion of polylactic acid and polybutylene succinate, that significantly prolonged the shelf-life of red grapes from 8 to 12 days by delaying the loss of weight, loss of hardness, and reduction in soluble solid content after harvesting. Further mechanistic study showed that this modified atmosphere film delayed the senescence of harvested red grape, the phenomenon that was highly related to the lower active oxygen species production and higher antioxidant enzyme activity compared to the non-packaged grape. The proposed continuous and dynamic microenvironment regulation system is a promising method to study the mechanisms of respiratory metabolism in fruit and extends food shelf-life while reducing food waste. PRACTICAL APPLICATION: In this study, we designed a means to microenvironmental regulatory packaging that directly creates a continuous, dynamic, and monitorable microenvironment. To ensure that the fruit inside the package underwent coordinated aerobic and anaerobic respiration, we melt-extruded polylactic acid (PLA) and polybutylene succinate (PBS) to form a homogeneous biodegradable film. We demonstrated that the best preservation results were achieved with a film comprising an 80/20 PLA-to-PBS ratio. This film can prolong the shelf-life of fruits by regulating respiratory metabolism.

NR1H4-mediated circRHOBTB3 modulates the proliferation, metastasis, and Warburg effects of cervical cancer through interacting with IGF2BP3.

Globally, cervical cancer (CC) ranks as the fourth most common cancer and the most lethal malignancy among females of reproductive age. The incidence of CC is increasing in low-income countries, with unsatisfactory outcomes and long-term survival for CC patients. Circular RNAs (CircRNAs) are promising therapeutics that target multiple cancers. In this study, we investigated the tumorigenic role of circRHOBTB3 in CC, showing that circRHOBTB3 is highly expressed in CC cells and circRHOBTB3 knockdown also repressed CC proliferation, migration, invasion, and the Warburg effects. CircRHOBTB3 interacted with the RNA-binding protein, IGF2BP3, to stabilize its expression in CC cells and is putatively transcriptionally regulated by NR1H4. In conclusion, this novel NR1H4/circRHOBTB3/IGF2BP3 axis may provide new insights into CC pathogenesis.

Complexin-1 regulated assembly of single neuronal SNARE complex revealed by single-molecule optical tweezers.

The dynamic assembly of the Synaptic-soluble N-ethylmaleimide-sensitive factor Attachment REceptor (SNARE) complex is crucial to understand membrane fusion. Traditional ensemble study meets the challenge to dissect the dynamic assembly of the protein complex. Here, we apply minute force on a tethered protein complex through dual-trap optical tweezers and study the folding dynamics of SNARE complex under mechanical force regulated by complexin-1 (CpxI). We reconstruct the clamp and facilitate functions of CpxI in vitro and identify different interplay mechanism of CpxI fragment binding on the SNARE complex. Specially, while the N-terminal domain (NTD) plays a dominant role of the facilitate function, CTD is mainly related to clamping. And the mixture of 1-83aa and CTD of CpxI can efficiently reconstitute the inhibitory signal identical to that the full-length CpxI functions. Our observation identifies the important chaperone role of the CpxI molecule in the dynamic assembly of SNARE complex under mechanical tension, and elucidates the specific function of each fragment of CpxI molecules in the chaperone process.

Effect of platelet-rich plasma vs standard management for the treatment of diabetic foot ulcer wounds: A meta-analysis.

We performed a meta-analysis to evaluate the effect of platelet-rich plasma vs standard management for the treatment of diabetic foot ulcer wounds. A systematic literature search up to March 2022 was performed and 1435 subjects with diabetic foot ulcer wounds at the baseline of the studies; 723 of them were treated with platelet-rich plasma, and 712 used control. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated to assess the effect of platelet-rich plasma vs standard management for the treatment of diabetic foot ulcer wounds using the dichotomous method with a random or fixed-effect model. The use of autologous platelet-rich plasma resulted in significantly higher complete-healed diabetic foot ulcer wounds compared with control (OR, 1.95; 95% CI, 1.49-2.56, P < 0.001). The use of allogeneic platelet-rich plasma resulted in significantly higher complete-healed diabetic foot ulcer wounds compared with control (OR, 6.19; 95% CI, 2.32-16.56, P < 0.001). The use of autologous and allogeneic platelet-rich plasma resulted in significantly higher complete-healed diabetic foot ulcer wounds compared with control. Though, the analysis of outcomes should be with caution because of the low number of studies in certain comparisons, for example, allogeneic platelet-rich plasma compared with control.

Dynamic Kinetic Resolution of ß-Substituted α-Diketones via Asymmetric Transfer Hydrogenation.

Developing innovative dynamic kinetic resolution (DKR) modes and achieving the highly regio- and enantioselective semihydrogenation of unsymmetrical α-diketones are two formidable challenges in the field of contemporary asymmetric (transfer) hydrogenation. In this work, we report the highly regio- and stereoselective asymmetric semi-transfer hydrogenation of unsymmetrical α-diketones through a unique DKR mode, which features the reduction of the carbonyl group distal from the labile stereocenter, while the proximal carbonyl remains untouched. Moreover, the protocol affords a variety of enantioenriched acyclic ketones with α-hydroxy-α'-C(sp2)-functional groups, which represent a new product class that has not been furnished in known arts. The utilities of the products have been demonstrated in a series of further transformations including the rapid synthesis of drug molecules. Density functional theory calculations and plenty of control experiments have also been conducted to gain more mechanistic insights into the highly selective semihydrogenation.

Chemical component analysis of the traditional Chinese medicine Guipi Tang and its effects on major depressive disorder at molecular level.

Ethnopharmacological relevance: Guipi Tang (GPT) is a widely used traditional Chinese medicine that is used to treat major depressive disorder. However, the molecular mechanisms of its effects remain unclear. Aim of the study: This study aimed to investigate the antidepressant-like effects of GPT and explore its underlying molecular mechanisms. Materials and methods: Male Sprague-Dawley rats were subjected to a chronic unpredictable mild stress (CUMS) procedure and treated with various doses of GPT, with fluoxetine treatment as a positive control. Behavioural tests (including sucrose preference test, novelty-suppressed feeding test, open-field test and forced swim test), terminal deoxynucleotidyl transferase dUTP nick end labeling and enzyme-linked immunosorbent assay were conducted. The levels of Bax, Bcl-2, cleaved caspase-3, PI3K, p-PI3K, AKT, p-AKT, BDNF, TrkB and CREB or p-CREB were assessed at the protein level using western blotting or immunofluorescence. Results: GPT consists of mainly known drugs, such as liquiritin and ginsenosides. It reversed depressive behaviours and decreased cell apoptosis in the hippocampi of CUMS rats. It significantly upregulated the protein level of Bax, p-Akt, p-PI3K, BDNF, TrkB and p-CREB and downregulated the level of cleaved caspase-3 and Bcl-2. Conclusions: GPT had anti-depressive activity as indicated by the amelioration of depression-like behaviour and the inhibition of hippocampal neuronal apoptosis in CUMS rats. This inhibition was mediated partly by modulating the PI3K/Akt and/or BDNF/TrkB/CREB pathway, in which, glycosides, the main components of GPT, might be involved.

Oxa-Nazarov Cyclization-Michael Addition Sequence for the Rapid Construction of Dihydrofuranones.

The Nazarov cyclization has been established as a powerful tool in constructing cyclopentenone skeletons. In sharp contrast, oxa-Nazarov cyclization that affords dihydrofuranones, a new type of product, has been less explored. In this work, we report the I2-catalyzed oxa-Nazarov cyclization-Michael addition cascade between vinyl α-diketones and enones. The protocol allows access to a range of functionalized dihydrofuranones with good to high yields, and diverse further transformations on the products have been achieved. Furthermore, the mechanistic studies reveal that the 1,2-hydride shift occurs simultaneously during the dihydrofuranone formation.

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

Inhibition of TGFß1/Smad pathway by NF-κB induces inflammation leading to poor wound healing in high glucose.

This study mainly analyzed the relationship between nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor-ß (TGFß1)/Smad under high glucose environment and its influence on wound healing. Fibroblast NIH-3T3 was used to analyze the effect of high concentration glucose (20 nmol/mL) on cell viability, migration ability, inflammation level and NF-κB pathway. Pyrrolidinedithiocarbamate (PDTC) was used to inhibit NF-κB for rescue experiments. Diabetic mice were used to construct wound healing models. Recombinant TGF-ß1 was used to promote wound healing in diabetic mice. FSL-1 was applied to activate NF-κB to verify the mechanism. High glucose inhibited cell viability and migration ability, promoted the expression of TNF-α, IL-6 and IL-1ß, induced the activation of NF-κB pathway in fibroblasts. Inhibition of NF-κB not only blocked the decrease in cell viability and migration ability induced by high glucose, but also relieved the release of inflammatory factors. TGF-ß1 activated the TGF-ß1/Smad pathway and promoted wound healing in diabetic mice. Activating the NF-κB pathway not only inhibited the activation of the TGF-ß1/Smad pathway, but also alleviated the promoting effect of TGF-ß1 on wound healing. In a high glucose environment, the activation of NF-κB may inhibit the function of fibroblasts by inhibiting the TGF-ß1/Smad pathway, resulting in poor wound healing.

Comparison of the Effects of Open Surgery and Minimally Invasive Surgery on the Achilles Tendon Rupture Healing Based on Angiogenesis.

Objective: To compare the effect of three different surgical methods on rabbit Achilles tendon rupture. Methods: The Achilles tendon transection model was constructed by cutting off the inner half of the Achilles tendon. Rabbits were divided into 4 groups: model group, open surgery (OS) group, minimally invasive surgery (MS) group, and conservative treatment (CT) group. Biomechanical evaluation, H&E, and Picrosirius Red staining were applied to evaluate the histological changes and healing. RT-qPCR, Western blot, ELISA, and IHC staining were used to detect the expression of COLIII, IL-1ß, TNF-α, IL-6, CD31, VEGF, bFGF, and TGF-ß1. Results: Different surgery treatments significantly alleviated the histological changes in rabbits. The tension and elasticity of the Achilles tendon were significantly increased after surgery. In addition, surgery treatments notably alleviated the inflammatory responses in vivo via downregulation of IL-1ß, TNF-α, and IL-6 and promoted the tube formation in tissues through upregulating VEGF, bFGF, TGF-ß1, and CD31. Furthermore, MS exhibited best therapeutic efficiency on Achilles tendon rupture healing, compared with OS or CT. Conclusions: Our research revealed the superiority of MS in Achilles tendon rupture treatment at the molecular level compared with OS or CT.

MiR-192-5p Alleviated Fibrosis and Inflammatory Responses of Tendon Cells by Targeting NFAT5.

Objective: To explore the effect of microRNA (miR)-192-5p on the inflammatory and fibrotic responses of tendon cells. Methods: Tendon cells were treated with transforming growth factor-ß1 (TGF-ß1). The expression of miR-192-5p and nuclear factor of activated T cells 5 (NFAT5) in tendon cells were detected by RT-qPCR. The expressions of inflammatory and fibrosis-related factors were detected by RT-qPCR and Western blot. MiR-192-5p binds to NFAT5 targeting by TargetScan and dual-luciferase reporter gene assay. The expression of the NFAT5 gene was detected by RT-qPCR and Western blot. Detection of apoptosis in tendon cells by flow cytometry. Results: MiR-192-5p was downregulated in tendon cells, and the expression level gradually decreased with the prolong of TGF-ß1 treatment. The expression of NFAT5 increased with the treatment time of TGF-ß1. The expression of miR-192-5p decreased collagen III (COLIII), α smooth muscle actin (α-SMA), matrix metalloproteinase- (MMP-) 1, and MMP-8 expression, thereby inhibiting TGF-ß1-induced fibrosis in tendon cells. The expression of miR-192-5p decreased the expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß, thereby alleviating TGF-ß1-induced inflammatory response and reduce apoptosis in tendon cells. NFAT5 is a direct target of miR-192-5p in tendon cells. The upregulation of NFAT5 reversed the effect of miR-192-5p on the fibrotic activity and inflammatory response of TGF-ß1-stimulated tendon cells. Conclusions: MiR-192-5p alleviates fibrosis and inflammatory responses of tendon cells by targeting NFAT5.

Stability of drugs of abuse in synthetic oral fluid investigated using a simple "dilute and inject" method of analysis.

Human oral fluid is well established as a matrix for drug screening, particularly in the workplace. The need to synthesise synthetic oral fluid (SOF) has been recognised in order to overcome human oral fluid's composition variability. We have used SOF spiked with six common drugs of abuse or their primary metabolites: morphine, amfetamine, benzoylecgonine, cocaine, diazepam, and (-)-Δ9 -tetrahydrocannabinol (THC) in order to assess the suitability of this matrix for quality assurance purposes. For confirmation of a drug screening test, controls and spiked standards are normally required. All our analytes were detected by LC-MS/MS using a quick and easy "dilute and inject" sample preparation approach as opposed to relatively slower solid-phase extraction. The limit of detection (LOD) was 10 ng/ml for diazepam and THC and 5 ng/ml for morphine, amfetamine, benzoylecgonine and cocaine. Validation results showed good accuracy as well as inter- and intra-assay precision (CV [%] < 5). Our work highlighted the importance of adding Tween® 20 to the SOF and calibrants to reduce losses when handling THC. Furthermore, drug stability was tested at various temperatures (5°C, 20°C and 40°C), for a number of days or after freeze-thaw cycles. Recommendations regarding storage are provided, the spiked SOF being stable at 5°C for up to 1 week without significant drug concentration loss.

Mechanism of the Curative Effect of Wen-Shen-Jian-Pi Prescription in the Treatment of Amyotrophic Lateral Sclerosis.

Objective: To study the mechanism of the effect of Wen-Shen-Jian-Pi (WSJP) prescription on an ALS model comprising mice knocked out for an encoding RNA editing, mice (AR2). Methods: Twenty-four transgenic AR2 mice were randomly divided into a vehicle group, a low dose WSJP group (15 mg), a medium-dose WSJP group (30 mg), and a high-dose WSJP group (45 mg) (all n = 6 per group). In the treatment groups, the WSJP prescription was given once a day while the vehicle group was fed the same volume of water. The weekly changes in body weight, rotarod test, and grip strength were used to detect the changes in the AR2 and changes of the number of normal mitochondria, abnormal mitochondria, and autophagosomes in injured spinal cord cells were used to evaluate the pathogenetic effects of WSJP treatment. Results: The WSJP-treated AR2 mice gained weight more quickly from 8 weeks, and showed active behavior and displayed significantly better constant rotarod scores and grip strengths during the experiment compared with those of the vehicle AR2 mice. The number of normal mitochondria in the WSJP-treated AR2 mice had significantly more normal mitochondria than the vehicle group, while the numbers of abnormal mitochondria and autophagosomes were greatly decreased compared with those in the vehicle group. Conclusion: The WSJP prescription could delay the decline in motor function of ALS model mice by reducing the degeneration of neurons. The potential of WSJP to treat ALS should be assessed in a clinical trial.

Malnutrition and Risk of Mortality in Ischemic Stroke Patients Treated With Intravenous Thrombolysis.

Background and Purpose: Malnutrition is highly prevalent in ischemic stroke patients. We aimed to investigate whether malnutrition indexes may be useful in predicting mortality at 90 days in ischemic stroke patients treated with intravenous thrombolysis. Methods: We retrospectively analyzed consecutive patients who underwent thrombolytic therapy at three comprehensive stroke centers. Malnutrition was assessed using the controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI). Results: Of 979 patients (mean age, 66.8 years; males, 63.6%) included in this study, 91 (9.3%; 95% confidence interval [CI]: 8.4-10.2%) died at 3-month follow up. According to the CONUT, GNRI, and PNI scores, 9.9, 33.7, and 7.0% of patients were moderately or severely malnourished, respectively; 64.0% were at least mildly malnourished by at least 1 malnutrition index. In the multivariate regression model after adjusting for potential confounders, malnutrition (severe risk versus normal nutritional status) was significantly associated with an increased risk of mortality for CONUT scores (adjusted odds ratio [OR] 16.16, 95%CI, 7.86-67.11; P < 0.001), GNRI scores (adjusted OR 9.82, 4.10-23.51; P < 0.001) and PNI scores (adjusted OR 12.74, 5.56-29.19; P < 0.001). Similar results were found when the malnutrition scores were analyzed as continuous variables. Adding the three malnutrition indexes to models containing conventional risk factors significantly improved risk reclassification for 3-month mortality. Conclusion: Our study showed that malnutrition may be associated with a higher risk of mortality at 3 months in ischemic stroke after intravenous thrombolysis.

A High-Performance In-Memory Photodetector Realized by Charge Storage in a van der Waals MISFET.

The emerging data-intensive applications in optoelectronics are driving innovation toward the fused integration of sensing, memory, and computing to break through the restrictions of the von Neumann architecture. However, the present photodetectors with only optoelectronic conversion functions cannot satisfy the growing demands of the multifunctions required in single devices. Here, a novel route for the integration of non-volatile memory into a photodetector is proposed, with a WSe2 /h-BN van der Waals heterostructure on a Si/SiO2 substrate to realize in-memory photodetection. This photodetector exhibits an ultrahigh readout photocurrent of 3.4 µA and photoresponsivity of 337.8 A W-1 in the solar-blind wavelength region, together with an extended retention time of more than 10 years. Furthermore, the charge-storage-based non-volatile mechanism of h-BN/SiO2 is successfully proven through a novel analysis of in situ optoelectronic electron energy-loss spectroscopy. These results represent a leap forward to future applications and insightful mechanisms of in-memory photodetection.

Enhancer RNA SLIT2 Inhibits Bone Metastasis of Breast Cancer Through Regulating P38 MAPK/c-Fos Signaling Pathway.

BACKGROUND: Breast cancer (BRCA) is the most common cancer in women, while the bones are one of the most common sites of metastasis. Although new diagnostic methods or radiation or chemotherapies and targeted therapies have made huge advances, the occurrence of bone metastasis is also linked with poorer survival. Enhancer RNAs (eRNAs) have been demonstrated to participate in the progression of tumorigenesis and metastasis. However, the role of eRNAs in BRCA bone metastasis remains largely unclear. METHOD: Gene expression profiling of 1,211 primary BRCA and 17 bone metastases samples were retrieved from The Cancer Genome Atlas (TCGA) database, and the significant prognostic eRNAs were identified by Cox regression and least absolute shrinkage and selection operator (LASSO) regression. The acceptable accuracy and discrimination of the nomogram were indicated by the receiver operating characteristic (ROC) and the calibration curves. Then target genes of eRNA, immune cell percentage by CIBERSORT analysis, immune genes by single-sample gene set enrichment analysis (ssGSEA), hallmark of cancer signaling pathway by gene set variation analysis (GSVA), and reverse phase protein array (RPPA) protein chip were used to build a co-expression regulation network and identified the key eRNAs in bone metastasis of BRCA. Finally, Cell Counting Kit-8 (CCK8) assay, cell cycle assay, and transwell assay were used to study changes in cell proliferation, migration, and invasiveness. Immunoprecipitation assay and Western blotting were used to test the interaction and the regulation signaling pathways. RESULTS: The 27 hub eRNAs were selected, and a survival-related linear risk assessment model with a relatively high accuracy (area under curve (AUC): 0.726) was constructed. In addition, seven immune-related eRNAs (SLIT2, CLEC3B, LBPL1, FRY, RASGEF1B, DST, and ITIH5) as prognostic signatures for bone metastasis of BRCA were further confirmed by LASSO and multivariate Cox regression and CIBERSORT analysis. Finally, in vitro assay demonstrated that overexpression of SLIT2 reduced proliferation and metastasis in BRCA cells. Using high-throughput co-expression regulation network, we identified that SLIT2 may regulating P38 MAPK/c-Fos signaling pathway to promote the effects of metastasis. CONCLUSION: Based on the co-expression network for bone metastasis of BRCA, we screened key eRNAs to explore a prognostic model in predicting the bone metastasis by bioinformatics analysis. Besides, we identified the potential regulatory signaling pathway of SLIT2 in BRCA bone metastasis, which provides a promising therapeutic strategy for metastasis of BRCA.