Assessing the predictability of surrogate safety measures as crash precursors based on vehicle trajectory data prior to crashes.

This study aims to investigate the predictability of surrogate safety measures (SSMs) for real-time crash risk prediction. We conducted a year-long drone video collection on a busy freeway in Nanjing, China, and collected 20 rear-end crashes. The predictability of SSMs was defined as the probability of crash occurrence when using SSMs as precursors to crashes. Ridge regression models were established to explore contributing factors to the predictability of SSMs. Four commonly used SSMs were tested in this study. It was found that modified time-to-collision (MTTC) outperformed other SSMs when the early warning capability was set at a minimum of 1 s. We further investigated the cost and benefit of SSMs in safety interventions by evaluating the number of necessary predictions for successful crash prediction and the proportion of crashes that can be predicted accurately. The result demonstrated these SSMs were most efficient in proactive safety management systems with an early warning capability of 1 s. In this case, 308, 131, 281, and 327,661 predictions needed to be made before a crash could be successfully predicted by TTC, MTTC, DRAC, and PICUD, respectively, achieving 75 %, 85 %, 35 %, and 100 % successful crash identifications. The ridge regression results indicated that the predefined threshold had the greatest impact on the predictability of all tested SSMs.

Lightweight Knowledge Distillation-Based Transfer Learning Framework for Rolling Bearing Fault Diagnosis.

Compared to fault diagnosis across operating conditions, the differences in data distribution between devices are more pronounced and better aligned with practical application needs. However, current research on transfer learning inadequately addresses fault diagnosis issues across devices. To better balance the relationship between computational resources and diagnostic accuracy, a knowledge distillation-based lightweight transfer learning framework for rolling bearing diagnosis is proposed in this study. Specifically, a deep teacher-student model based on variable-scale residual networks is constructed to learn domain-invariant features relevant to fault classification within both the source and target domain data. Subsequently, a knowledge distillation framework incorporating a temperature factor is established to transfer fault features learned by the large teacher model in the source domain to the smaller student model, thereby reducing computational and parameter overhead. Finally, a multi-kernel domain adaptation method is employed to capture the feature probability distribution distance of fault characteristics between the source and target domains in Reproducing Kernel Hilbert Space (RKHS), and domain-invariant features are learned by minimizing the distribution distance between them. The effectiveness and applicability of the proposed method in situations of incomplete data across device types were validated through two engineering cases, spanning device models and transitioning from laboratory equipment to real-world operational devices.

Therapeutic potential of ADSC-EV-derived lncRNA DLEU2: A novel molecular pathway in alleviating sepsis-induced lung injury via the miR-106a-5p/LXN axis.

This study investigates the molecular mechanisms by which extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSCs) promote M2 polarization of macrophages and thus reduce lung injury caused by sepsis. High-throughput sequencing was used to identify differentially expressed genes related to long non-coding RNA (lncRNA) in ADSC-derived EVs (ADSC-EVs) in sepsis lung tissue. Weighted gene co-expression network analysis (WGCNA) was employed to predict the downstream target genes of the lncRNA DLEU2. The RNAInter database predicted miRNAs that interact with DLEU2 and LXN. Functional and pathway enrichment analyses were performed using GO and KEGG analysis. A mouse model of sepsis was established, and treatment with a placebo or ADSC-EVs was administered, followed by RT-qPCR analysis. ADSC-EVs were isolated and identified. In vitro cell experiments were conducted using the mouse lung epithelial cell line MLE-12, mouse macrophage cell line RAW264.7, and mouse lung epithelial cell line (LEPC). ADSC-EVs were co-cultured with RAW264.7 and MLE-12/LEPC cells to study the regulatory mechanism of the lncRNA DLEU2. Cell viability, proliferation, and apoptosis of lung injury cells were assessed using CCK-8, EdU, and flow cytometry. ELISA was used to measure the levels of inflammatory cytokines in the sepsis mouse model, flow cytometry was performed to determine the number of M1 and M2 macrophages, lung tissue pathology was evaluated by H&E staining, and immunohistochemistry was conducted to examine the expression of proliferation- and apoptosis-related proteins. High-throughput sequencing and bioinformatics analysis revealed enrichment of the lncRNA DLEU2 in ADSC-EVs in sepsis lung tissue. Animal and in vitro cell experiments showed increased expression of the lncRNA DLEU2 in sepsis lung tissue after treatment with ADSC-EVs. Furthermore, ADSC-EVs were found to transfer the lncRNA DLEU2 to macrophages, promoting M2 polarization, reducing inflammation response in lung injury cells, and enhancing their viability, proliferation, and apoptosis inhibition. Further functional experiments indicated that lncRNA DLEU2 promotes M2 polarization of macrophages by regulating miR-106a-5p/LXN, thereby enhancing the viability and proliferation of lung injury cells and inhibiting apoptosis. Overexpression of miR-106a-5p could reverse the biological effects of ADSC-EVs-DLEU2 on MLE-12 and LEPC in vitro cell models. Lastly, in vivo animal experiments confirmed that ADSC-EVs-DLEU2 promotes high expression of LXN by inhibiting the expression of miR-106a-5p, further facilitating M2 macrophage polarization and reducing lung edema, thus alleviating sepsis-induced lung injury. lncRNA DLEU2 in ADSC-EVs may promote M2 polarization of macrophages and enhance the viability and proliferation of lung injury cells while inhibiting inflammation and apoptosis reactions, thus ameliorating sepsis-induced lung injury in a mechanism involving the regulation of the miR-106a-5p/LXN axis.

Constructing Innovative Covalent and Noncovalent Compound Libraries: Insights from 3D Protein-Ligand Interactions.

Noncovalent interactions between small-molecule drugs and protein targets assume a pivotal role in drug design. Moreover, the design of covalent inhibitors, forming covalent bonds with amino acid residues, requires rational reactivity for their covalent warheads, presenting a key challenge as well. Understanding the intricacies of these interactions provides a more comprehensive understanding of molecular binding mechanisms, thereby guiding the rational design of potent inhibitors. In this study, we adopted the fragment-based drug design approach, introducing a novel methodology to extract noncovalent and covalent fragments according to distinct three-dimensional (3D) interaction modes from noncovalent and covalent compound libraries. Additionally, we systematically replaced existing ligands with rational fragment substitutions, based on the spatial orientation of fragments in 3D space. Furthermore, we adopted a molecular generation approach to create innovative covalent inhibitors. This process resulted in the recombination of a noncovalent compound library and several covalent compound libraries, constructed by two commonly encountered covalent amino acids: cysteine and serine. We utilized noncovalent ligands in KLIFS and covalent ligands in CovBinderInPDB as examples to recombine noncovalent and covalent libraries. These recombined compound libraries cover a substantial portion of the chemical space present in the original compound libraries and exhibit superior performance in terms of molecular scaffold diversity compared to the original compound libraries and other 11 commercial libraries. We also recombined BTK-focused libraries, and 23 compounds within our libraries have been validated by former researchers to possess potential biological activity. The establishment of these compound libraries provides valuable resources for virtual screening of covalent and noncovalent drugs targeting similar molecular targets.

Metabolic reprogramming in skin wound healing.

Metabolic reprogramming refers to the ability of a cell to alter its metabolism in response to different stimuli and forms of pressure. It helps cells resist external stress and provides them with new functions. Skin wound healing involves the metabolic reprogramming of nutrients, such as glucose, lipids, and amino acids, which play vital roles in the proliferation, differentiation, and migration of multiple cell types. During the glucose metabolic process in wounds, glucose transporters and key enzymes cause elevated metabolite levels. Glucose-mediated oxidative stress drives the proinflammatory response and promotes wound healing. Reprogramming lipid metabolism increases the number of fibroblasts and decreases the number of macrophages. It enhances local neovascularization and improves fibrin stability to promote extracellular matrix remodelling, accelerates wound healing, and reduces scar formation. Reprogramming amino acid metabolism affects wound re-epithelialization, collagen deposition, and angiogenesis. However, comprehensive reviews on the role of metabolic reprogramming in skin wound healing are lacking. Therefore, we have systematically reviewed the metabolic reprogramming of glucose, lipids, and amino acids during skin wound healing. Notably, we identified their targets with potential therapeutic value and elucidated their mechanisms of action.

Interface-Engineered 2D Heterojunction with Photoelectric Dual Gain: Mxene@MOF-Enhanced SPR Spectroscopy for Direct Sensing of Exosomes.

MXene is widely used in the construction of optoelectronic interfaces due to its excellent properties. However, the hydrophilicity and metastable surface of MXene lead to its oxidation behavior, resulting in the degradation of its various properties, which seriously limits its practical application. In this work, a 2D metal-organic framework (2D MOF) with matching 2D morphology, excellent stability performance, and outstanding optoelectronic performance is grown in situ on the MXene surface through heterojunction engineering to suppress the direct contact between reactive molecules and the inner layer material without affecting the original advantages of MXene. The photoelectric dual gain MXene@MOF heterojunction is confirmed. As a photoelectric material, its properties are highly suitable for the demand of interface sensitization layer materials of surface plasmon resonance (SPR). Therefore, using SPR as a platform for the application of this interface material, the performance of MXene@MOF and its potential mechanism to enhance SPR are analyzed in depth using experiments combined with simulation calculations (FDTD/DFT). Finally, the MXene@MOF/peptides-SPR sensor is constructed for rapid and sensitive detection of the cancer marker exosomes to explore its potential in practical applications. This work offers a forward-looking strategy for the design of interface materials with excellent photoelectric performance.

"Fast First and Then Slowly" Steroid-Tapering Regimen in Managing Corticoid-Sensitive Patients With Severe Immunotherapy Complications After Anti-PD-(L)1 Therapy for Cancer.

Background: We aimed to assess the efficacy of the "fast first and then slowly" steroid-tapering regimen used in managing corticoid-sensitive patients with severe irAE after anti-PD-(L)1 therapy. Corticosteroids are the primary therapy for severe immune-related adverse events (irAEs). Less is known about the standard steroid-tapering regimen for corticoid-sensitive patients. Methods: This study was a single-center, retrospective medical record review of patients with severe irAE after anti-PD-(L)1 treatment for cancer from October 13, 2021 to October 20, 2022. The efficacy was assessed by Common Terminology Criteria for Adverse Events (CTCAE) grading system. Results: Among the 187 patients with severe irAEs associated with immune checkpoint inhibitors (ICIs), 136 (72.7%) cases were corticoid-sensitive, and 96 (51.3%) cases were scheduled "fast first and then slowly" steroid-tapering regimen. And of these, 87 (90.6%) cases got irAEs solution. Conclusions: The "fast first and then slowly" steroid-tapering regimen stayed shorter in the hospital. More studies are needed to confirm this efficacy and find more details about the steroid-tapering regimen.

circSSPO boosts growth of esophageal squamous cell carcinoma through upregulation of micrRNA-6820-5p-mediated KLK8 and PKD1 expression.

Investigation on a competitive endogenous RNA (ceRNA) network attracted lots of attention due its function in cancer regulation. Here, we probed into the possible molecular mechanism of circSSPO/microRNA-6820-5p (miR-6820-5p)/kallikrein-related peptidase 8 (KLK8)/PKD1 network in the esophageal squamous cell carcinoma (ESCC). Following whole-transcriptome sequencing and differential analysis in collected ESCC tissue samples, circRNA-miRNA-mRNA regulatory network affecting ESCC was investigated. After interaction measurement among circSSPO/miR-6820-5p/KLK8/PKD1, their regulatory roles in ESCC cell functions in vitro and xenograft tumor growth and lung metastasis in vivo were analyzed. The bioinformatics prediction and sequencing results screened that circSSPO, miR-6820-5p, KLK8, and PKD1 were associated with ESCC development. In ESCC, miR-6820-5p was expressed at very low levels, while circSSPO, KLK8, and PKD1 were highly expressed. In vitro cell experiments further proved that circSSPO competitively inhibited miR-6820-5p to induce ESCC cell malignant properties. Moreover, knockdown of KLK8 or PKD1 inhibited ESCC cell malignant properties. circSSPO also promoted the tumorigenic and metastasis of ESCC through the upregulation of KLK8 and PKD1 expression in vivo. We found that circSSPO was an oncogenic circRNA that was significantly abundant in ESCC tissues and circSSPO exhibited an oncogenic activity in ESCC by elevating expression of KLK8 and PKD1 through suppressing miR-6820-5p expression.

miR-214 could promote myocardial fibrosis and cardiac mesenchymal transition in VMC mice through regulation of the p53 or PTEN-PI3K-Akt signali pathway, promoting CF proliferation and inhibiting its ng pathway.

INTRODUCTION: This study aimed to investigate the role of miR-214 in the bidirectional regulation of p53 and PTEN and its influence on myocardial fibrosis and cardiac mesenchymal transformation in mice with viral myocarditis (VMC). METHODS: The study established a VMC model in BALB/c mice by injecting them with the CVB3 virus intraperitoneally. Techniques such as ELISA, H&E staining, Masson staining, immunohistochemical staining, RT-qPCR, western blot, and dual-luciferase reporter gene assay were used to detect the expression levels of relevant factors in tissues and cells. Isolation and culture of cardiac fibroblasts (CFs) were also conducted. RESULTS: The study found that miR-214 bidirectional regulation of p53 and PTEN promotes myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. The expression levels of collagen-related peptides, inflammatory-related factors, miR-214, mesenchymal transformation-related factors, and fibrosis-related factors were significantly increased, while the expression levels of p53, PTEN, and epithelial/endothelial cell phenotype marker factors were significantly decreased. Downregulation of miR-214 or upregulation of p53 and PTEN expression inhibited inflammatory cell and fibroblast infiltration in VMC mouse myocardial tissue. It reduced the proliferation ability while increasing the apoptosis of cardiac fibroblasts. CONCLUSION: miR-214 plays a significant role in the bidirectional inhibition of p53 and PTEN, which leads to myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. Downregulation of miR-214 or upregulation of p53 and PTEN expression may provide potential therapeutic targets for treating VMC-induced cardiac fibrosis and mesenchymal transformation.

Monocyte-derived exosomal XIST exacerbates acute lung injury by regulating the miR-448-5p/HMGB2 axis.

Monocyte-derived exosomes (Exos) have been implicated in inflammation-related autoimmune/inflammatory diseases via transferring bioactive cargoes to recipient cells. The purpose of this study was to investigate the possible effect of monocyte-derived Exos on the initiation and the development of acute lung injury (ALI) by delivering long non-coding RNA XIST. Key factors and regulatory mechanisms in ALI were predicted by bioinformatics methods. BALB/c mice were treated with lipopolysaccharide (LPS) to establish an ALI in vivo model and then injected with Exos isolated from monocytes transduced with sh-XIST to evaluate the effect of monocyte-derived exosomal XIST on ALI. HBE1 cells were co-cultured with Exos isolated from monocytes transduced with sh-XIST for further exploration of its effect. Luciferase reporter, RIP and RNA pull-down assays were performed to verify the interaction between miR-448-5p and XIST, miR-448-5p and HMGB2. miR-448-5p was significantly poorly expressed while XIST and HMGB2 were highly expressed in the LPS-induced mouse model of ALI. Monocyte-derived Exos transferred XIST into HBE1 cells where XIST competitively inhibited miR-448-5p and reduced the binding of miR-448-5p to HMGB2, thus upregulating the expression of HMGB2. Furthermore, in vivo data revealed that XIST delivered by monocyte-derived Exos downregulated miR-448-5p expression and up-regulated HMGB2 expression, ultimately contributing to ALI in mice. Overall, our results indicate that XIST delivered by monocyte-derived Exos aggravates ALI via regulating the miR-448-5p/HMGB2 signaling axis.

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OBJECTIVES: To construct a prognosis risk model based on long noncoding RNAs (lncRNAs) related to cuproptosis and to evaluate its application in assessing prognosis risk of bladder cancer patients. METHODS: RNA sequence data and clinical data of bladder cancer patients were downloaded from the Cancer Genome Atlas database. The correlation between lncRNAs related to cuproptosis and bladder cancer prognosis was analyzed with Pearson correlation analysis, univariate Cox regression, Lasso regression, and multivariate Cox regression. Then a cuproptosis-related lncRNA prognostic risk scoring equation was constructed. Patients were divided into high-risk and low-risk groups based on the median risk score, and the immune cell abundance between the two groups were compared. The accuracy of the risk scoring equation was evaluated using Kaplan-Meier survival curves, and the application of the risk scoring equation in predicting 1, 3 and 5-year survival rates was evaluated using receiver operating characteristic (ROC) curves. Univariate and multivariate Cox regression were used to screen for prognostic factors related to bladder cancer patients, and a prognostic risk assessment nomogram was constructed, the accuracy of which was evaluated with calibration curves. RESULTS: A prognostic risk scoring equation for bladder cancer patients was constructed based on nine cuproptosis-related lncRNAs. Immune infiltration analysis showed that the abundances of M0 macrophages, M1 macrophages, M2 macrophages, resting mast cells and neutrophils in the high-risk group were significantly higher than those in the low-risk group, while the abundances of CD8+ T cells, helper T cells, regulatory T cells and plasma cells in the low-risk group were significantly higher than those in the high-risk group (all P<0.05). Kaplan-Meier survival curve analysis showed that the total survival and progression-free survival of the low-risk group were longer than those of the high-risk group (both P<0.01). Univariate and multivariate Cox analysis showed that the risk score, age and tumor stage were independent factors for patient prognosis. The ROC curve analysis showed that the area under the curve (AUC) of the risk score in predicting 1, 3 and 5-year survival was 0.716, 0.697 and 0.717, respectively. When combined with age and tumor stage, the AUC for predicting 1-year prognosis increased to 0.725. The prognostic risk assessment nomogram for bladder cancer patients constructed based on patient age, tumor stage, and risk score had a prediction value that was consistent with the actual value. CONCLUSIONS: A bladder cancer patient prognosis risk assessment model based on cuproptosis-related lncRNA has been successfully constructed in this study. The model can predict the prognosis of bladder cancer patients and their immune infiltration status, which may also provide a reference for tumor immunotherapy.

Transcriptome sequencing and network pharmacology-based approach to reveal the effect and mechanism of Ji Chuan Jian against Parkinson's disease.

BACKGROUND: Ji Chuan Jian (JCJ), a classic Traditional Chinese Medicine (TCM) formula, has been widely applied in treating Parkinson's disease (PD) in China, However, the interaction of bioactive compounds from JCJ with the targets involved in PD remains elusive. METHODS: Based on the transcriptome sequencing and network pharmacology approaches, the chemical compounds of JCJ and gene targets for treating PD were identified. Then, the Protein-protein interaction (PPI) and "Compound-Disease-Target" (C-D-T) network were constructed by using of Cytoscape. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to these target proteins. Finally, AutoDock Vina was used for applying molecular docking. RESULTS: In the present study, a total number of 2669 differentially expressed genes (DEGs) were identified between PD and healthy controls using whole transcriptome RNA sequencing. Then, 260 targets of 38 bioactive compounds in JCJ were identified. Of these targets, 47 were considered PD-related targets. Based on the PPI degree, the top 10 targets were identified. In C-D-T network analysis, the most important anti-PD bioactive compounds in JCJ were determined. Molecular docking revealed that potential PD-related targets, matrix metalloproteinases-9 (MMP9) were more stably bound with naringenin, quercetin, baicalein, kaempferol and wogonin. CONCLUSION: Our study preliminarily investigated the bioactive compounds, key targets, and potential molecular mechanism of JCJ against PD. It also provided a promising approach for identifying the bioactive compounds in TCM as well as a scientific basis for further elucidating the mechanism of TCM formulae in treating diseases.

MIAT shuttled by tumor-secreted exosomes promotes paclitaxel resistance in esophageal cancer cells by activating the TAF1/SREBF1 axis.

Chemoresistance remains a major obstacle to the treatment of esophageal cancer (EC). Exosome-mediated transfer of long noncoding RNAs (lncRNAs) has recently been unveiled to correlate with the regulation of drug resistance in EC. This study aimed to investigate the physiological mechanisms by which exosome-encapsulated lncRNA myocardial infarction-associated transcript (MIAT) derived from tumor cells might mediate the paclitaxel (PTX) resistance of EC cells. First, MIAT was experimentally determined to be upregulated in PTX nonresponders and PTX-resistant EC cells. Silencing of MIAT in PTX-resistant EC cells decreased cell viability and enhanced apoptosis, corresponding to a reduced half-maximal inhibitory concentration (IC50 ) value. Next, exosomes were isolated from EC109 and EC109/T cells, and EC109 cells were cocultured with EC109/T-cell-derived exosomes. Accordingly, MIAT was revealed to be transmitted through exosomes from EC109/T cells to EC109 cells. Tumor-derived exosomes carrying MIAT increased the IC50 value of PTX and suppressed apoptosis in EC109 cells to promote PTX resistance. Furthermore, MIAT promoted the enrichment of TATA-box binding protein-associated Factor 1 (TAF1) in the promoter region of sterol regulatory element binding transcription factor 1 (SREBF1), as shown by a chromatin immunoprecipitation assay. This might be the mechanism by which MIAT could promote PTX resistance. Finally, in vivo experiments further confirmed that the knockdown of MIAT attenuated the resistance of EC cells to PTX. Collectively, these results indicate that tumor-derived exosome-loaded MIAT activates the TAF1/SREBF1 axis to induce PTX resistance in EC cells, providing a potential therapeutic target for overcoming PTX resistance in EC.

Color doppler ultrasound analysis of pathological myopia induced changes in retrobulbar blood flow and its relationship with characteristic changes in myopia.

Objective: To analyze changes in retrobulbar blood flow in patients with pathological myopia using color doppler ultrasound (CDU), and to explore the relationship of these changes with the characteristic changes resulting from myopia. Methods: One hundred and twenty patients who met the selection criteria in the ophthalmology department of He Eye Specialist Hospital from May 2020 to May 2022 were included in this study. Patients with normal vision (n=40) were considered Group-A, patients with low and moderate myopia (n=40) were considered Group-B, and patients with pathological myopia (n=40) were considered Group-C. All three groups underwent ultrasonography. The peak systolic blood flow velocity (PSV), end-diastolic blood flow velocity (EDV), and resistance index (RI) of the ophthalmic artery, central retinal artery, and posterior ciliary artery were recorded and compared, and the characteristics of these parameters and myopia severity were analyzed. Results: Pathological myopia resulted in significantly lower PSV and EDV of the ophthalmic artery, central retinal artery and posterior ciliary artery and higher RI values than patients with normal vision and low/moderate myopia (P<0.05). Pearson correlation analysis showed that retrobulbar blood flow changes were significantly correlated with age, eye axis, best corrected visual acuity, and retinal choroidal atrophy. Conclusion: CDU can objectively evaluate the retrobulbar blood flow changes in pathological myopia, and such blood flow changes are significantly correlated with the characteristic changes of myopia.

2D MOF-enhanced SPR sensing platform: Facile and ultrasensitive detection of Sulfamethazine via supramolecular probe.

Sulfamethazine (SMZ) is widely present in the environment and can cause severe allergic reactions and cancer in humans. Accurate and facile monitoring of SMZ is crucial for maintaining environmental safety, ecological balance, and human health. In this work, a real-time and label-free surface plasmon resonance (SPR) sensor was devised using a two-dimensional metal-organic framework with superior photoelectric performance as an SPR sensitizer. The supramolecular probe was incorporated at the sensing interface, allowing for the specific capture of SMZ from other analogous antibiotics through host-guest recognition. The intrinsic mechanism of the specific interaction of the supramolecular probe-SMZ was elucidated through the SPR selectivity test in combination with analysis by density functional theory, including p-π conjugation, size effect, electrostatic interaction, π-π stacking, and hydrophobic interaction. This method facilitates a facile and ultrasensitive detection of SMZ with a limit of detection of 75.54 pM. The accurate detection of SMZ in six environmental samples demonstrates the potential practical application of the sensor. Leveraging the specific recognition of supramolecular probes, this direct and simple approach offers a novel pathway for the development of novel SPR biosensors with outstanding sensitivity.

Capping-layer-mediated lattice mismatch and redox reaction in SrTiO3-based bilayers.

It is well known that the traditional two-dimensional electron system (2DES) hosted by the SrTiO3substrate can exhibit diverse electronic states by modifying the capping layer in heterostructures. However, such capping layer engineering is less studied in the SrTiO3-layer-carried 2DES (or bilayer 2DES), which is different from the traditional one on transport properties but more applicable to the thin-film devices. Here, several SrTiO3bilayers are fabricated by growing various crystalline and amorphous oxide capping layers on the epitaxial SrTiO3layers. For the crystalline bilayer 2DES, the monotonical reduction on the interfacial conductance, as well as carrier mobility, is recorded on increasing the lattice mismatch between the capping layers and epitaxial SrTiO3layer. The mobility edge raised by the interfacial disorders is highlighted in the crystalline bilayer 2DES. On the other hand, when increasing the concentration of Al with high oxygen affinity in the capping layer, the amorphous bilayer 2DES becomes more conductive accompanied by the enhanced carrier mobility but almost constant carrier density. This observation cannot be explained by the simple redox-reaction model, and the interfacial charge screening and band bending need to be considered. Moreover, when the capping oxide layers have the same chemical composition but with different forms, the crystalline 2DES with a large lattice mismatch is more insulating than its amorphous counterpart, and vice versa. Our results shed some light on understanding the different dominant role in forming the bilayer 2DES using crystalline and amorphous oxide capping layer, which may be applicable in designing other functional oxide interfaces.

The effect of electroacupuncture at ST25 on Parkinson's disease constipation through regulation of autophagy in the enteric nervous system.

The effectiveness and safety of electroacupuncture (EA) for constipation have been confirmed by numerous clinical studies and experiments, and there are also studies on the efficacy of EA for Parkinson's disease (PD) motor symptoms. However, there are few researches on EA for PD constipation. Autophagy is thought to be involved in the mechanistic process of EA in the central nervous system (CNS) intervention in Parkinson's pathology. However, whether it has the same effect on the enteric nervous system (ENS) has not been elucidated. Therefore, we investigated whether EA at Tianshu (ST25) acupoint promotes the clearance of α-Syn and damaged mitochondria aggregated in the ENS in a model of rotenone-induced PD constipation. This study evaluated constipation symptoms by stool characteristics, excretion volume, and water content, and the expression levels of colonic ATG5, LC3II, and Parkin were detected by Western Blot (WB) and Real-Time Quantitative PCR (RT-qPCR). The relationship between the location of α-Syn and Parkin in the colonic ENS was observed by immunofluorescence (IF). The results showed that EA intervention significantly relieved the symptoms of rotenone-induced constipation in PD rats, reversed the rotenone-induced down-regulation of colonic ATG5, LC3II, and Parkin expression, and the positional relationship between colonic α-Syn and Parkin proved to be highly correlated. It is suggested that EA might be helpful in treating PD constipation by modulating Parkin-induced mitochondrial autophagy.

Protective effect of cistanoside A on dopaminergic neurons in Parkinson's disease via mitophagy.

One of the main pathological features of Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra compacta (SNc). Cistanoside A (CA) has a strong neuroprotective effect in PD, but the exact mechanism is unclear. In the present study, the MPTP-stimulated mouse model of PD and MPP+ -treated PD model in the MES23.5 neuronal cell model of PD were used to investigate the neuroprotective effects of CA on PD and its potential mechanism. The in vivo experiment results indicated that CA improved the motor function in mice and increased the number of tyrosine hydroxylase positive cells in SNc. In vitro experiments showed that CA reduced the MPP+ -induced decrease in neurons and mitochondrial membrane potential and promoted the activation of autophagosomes. Furthermore, we found that CA promoted the recruitment of PINK1 and Parkin aggregation to impair mitochondrial membranes and inhibited mitochondrial damage via LC3- and p62-mediated autophagy. In conclusion, CA protects against MPTP-induced neurotoxicity in vivo and MPP+ -induced neurotoxicity in vitro, possibly by promoting the PINK1/Parkin/p62 pathway to accelerate the degradation of damaged mitochondria thereby reducing oxidative stress.