Sequence-Prescribed ß-Sheet for Enhanced Electron Tunneling: Boosting Interface Recognition and Electrochemical Measurement.

Peptide self-assemblies could leverage their specificity, stability, biocompatibility, and electrochemical activity to create functionalized interfaces for molecular sensing and detection. However, the dynamics within these interfaces are complex, with competing forces, including those maintaining peptide structures, recognizing analytes, and facilitating signal transmission. Such competition could lead to nonspecific interference, compromising the detection sensitivity and accuracy. In this study, a series of peptides with precise structures and controllable electron transfer capabilities were designed. Through examining their stacking patterns, the interplay between the peptides' hierarchical structures, their ability to recognize targets, and their conductivity were clarified. Among these, the EP5 peptide assembly was identified for its ability to form controllable electronic tunnels facilitated by π-stacking induced ß-sheets. EP5 could enhance the long-range conductivity, minimize nonspecific interference, and exhibit targeted recognition capabilities. Based on EP5, an electrochemical sensing interface toward the disease marker PD-L1 (programmed cell death ligand 1) was developed, suitable for both whole blood assay and in vivo companion diagnosis. It opens a new avenue for crafting electrochemical detection interfaces with specificity, sensitivity, and compatibility.

Visualization of the Ferroptosis in Atherosclerotic Plaques with Nanoprobe Engineered by Macrophage Cell Membranes.

Atherosclerosis (AS) is the root cause of cardiovascular diseases. Ferroptosis is characterized by highly iron-dependent lipid peroxidation and has been reported to play an important role in the pathogenesis of AS. Visualization of the ferroptosis process in atherosclerotic plaques is of great importance for diagnosing and treating AS. In this work, the rationally designed fluorescent probe FAS1 exhibited excellent advantages including large Stokes shift, sensitivity to environmental viscosity, good photostability, and improved water solubility. It also could co-locate with commercial lipid droplets (LDs) probes (BODIPY 493/503) well in RAW264.7 cells treated by the ferroptosis inducer. After self-assembly into nanoparticles and then encapsulation with macrophage membranes, the engineered FAS1@MM NPs could successfully target the atherosclerotic plaques in Western diet-induced apolipoprotein E knockout (ApoE-/-) mice and reveal the association of ferroptosis with AS through fluorescence imaging in vivo. This study may provide additional insights into the roles of ferroptosis in the diagnosis and treatment of AS.

The novel small molecule E0924G dually regulates bone formation and bone resorption through activating the PPARδ signaling pathway to prevent bone loss in ovariectomized rats and senile mice.

Osteoporosis is particularly prevalent among postmenopausal women and the elderly. In the present study, we investigated the effect of the novel small molecule E0924G (N-(4-methoxy-pyridine-2-yl)-5-methylfuran-2-formamide) on osteoporosis. E0924G significantly increased the protein expression levels of osteoprotegerin (OPG) and runt-related transcription factor 2 (RUNX2), and thus significantly promoted osteogenesis in MC3T3-E1 cells. E0924G also significantly decreased osteoclast differentiation and inhibited bone resorption and F-actin ring formation in receptor activator of NF-κB ligand (RANKL)-induced osteoclasts from RAW264.7 macrophages. Importantly, oral administration of E0924G in both ovariectomized (OVX) rats and SAMP6 senile mice significantly increased bone mineral density and decreased bone loss compared to OVX controls or SAMR1 mice. Further mechanistic studies showed that E0924G could bind to and then activate peroxisome proliferator-activated receptor delta (PPARδ), and the pro-osteoblast effect and the inhibition of osteoclast differentiation induced by E0924G were significantly abolished when PPARδ was knocked down or inhibited. In conclusion, these data strongly suggest that E0924G has the potential to prevent OVX-induced and age-related osteoporosis by dual regulation of bone formation and bone resorption through activation of the PPARδ signaling pathway.

A novel small-molecule PCSK9 inhibitor E28362 ameliorates hyperlipidemia and atherosclerosis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor precursor homologous domain A (EGF-A) of low-density lipoprotein receptor (LDLR) in the liver and triggers the degradation of LDLR via the lysosomal pathway, consequently leading to an elevation in plasma LDL-C levels. Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. Thus, PCSK9 is an innovative pharmacological target for treating hypercholesterolemia and atherosclerosis. In this study, we discovered that E28362 was a novel small-molecule PCSK9 inhibitor by conducting a virtual screening of a library containing 40,000 compounds. E28362 (5, 10, 20 µM) dose-dependently increased the protein levels of LDLR in both total protein and the membrane fraction in both HepG2 and AML12 cells, and enhanced the uptake of DiI-LDL in AML12 cells. MTT assay showed that E28362 up to 80 µM had no obvious toxicity in HepG2, AML12, and HEK293a cells. The effects of E28362 on hyperlipidemia and atherosclerosis were evaluated in three different animal models. In high-fat diet-fed golden hamsters, administration of E28362 (6.7, 20, 60 mg·kg-1·d-1, i.g.) for 4 weeks significantly reduced plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and PCSK9 levels, and reduced liver TC and TG contents. In Western diet-fed ApoE-/- mice (20, 60 mg·kg-1·d-1, i.g.) and human PCSK9 D374Y overexpression mice (60 mg·kg-1·d-1, i.g.), administration of E28362 for 12 weeks significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions in en face aortas and aortic roots. Moreover, E28362 significantly increased the protein expression level of LDLR in the liver. We revealed that E28362 selectively bound to PCSK9 in HepG2 and AML12 cells, blocked the interaction between LDLR and PCSK9, and induced the degradation of PCSK9 through the ubiquitin-proteasome pathway, which finally resulted in increased LDLR protein levels. In conclusion, E28362 can block the interaction between PCSK9 and LDLR, induce the degradation of PCSK9, increase LDLR protein levels, and alleviate hyperlipidemia and atherosclerosis in three distinct animal models, suggesting that E28362 is a promising lead compound for the treatment of hyperlipidemia and atherosclerosis.

Deep learning for in vivo near-infrared imaging.

Detecting fluorescence in the second near-infrared window (NIR-II) up to ∼1,700 nm has emerged as a novel in vivo imaging modality with high spatial and temporal resolution through millimeter tissue depths. Imaging in the NIR-IIb window (1,500-1,700 nm) is the most effective one-photon approach to suppressing light scattering and maximizing imaging penetration depth, but relies on nanoparticle probes such as PbS/CdS containing toxic elements. On the other hand, imaging the NIR-I (700-1,000 nm) or NIR-IIa window (1,000-1,300 nm) can be done using biocompatible small-molecule fluorescent probes including US Food and Drug Administration-approved dyes such as indocyanine green (ICG), but has a caveat of suboptimal imaging quality due to light scattering. It is highly desired to achieve the performance of NIR-IIb imaging using molecular probes approved for human use. Here, we trained artificial neural networks to transform a fluorescence image in the shorter-wavelength NIR window of 900-1,300 nm (NIR-I/IIa) to an image resembling an NIR-IIb image. With deep-learning translation, in vivo lymph node imaging with ICG achieved an unprecedented signal-to-background ratio of >100. Using preclinical fluorophores such as IRDye-800, translation of ∼900-nm NIR molecular imaging of PD-L1 or EGFR greatly enhanced tumor-to-normal tissue ratio up to ∼20 from ∼5 and improved tumor margin localization. Further, deep learning greatly improved in vivo noninvasive NIR-II light-sheet microscopy (LSM) in resolution and signal/background. NIR imaging equipped with deep learning could facilitate basic biomedical research and empower clinical diagnostics and imaging-guided surgery in the clinic.

SIRT1 Activator E1231 Alleviates Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Silencing information regulator 1 (SIRT1) was demonstrated to modulate cholesterol and lipid metabolism in NAFLD. Here, a novel SIRT1 activator, E1231, was studied for its potential improvement effects on NAFLD. C57BL/6J mice were fed a high-fat and high-cholesterol diet (HFHC) for 40 weeks to create a NAFLD mouse model, and E1231 was administered by oral gavage (50 mg/kg body weight, once/day) for 4 weeks. Liver-related plasma biochemistry parameter tests, Oil Red O staining, and hematoxylin-eosin staining results showed that E1231 treatment ameliorated plasma dyslipidemia, plasma marker levels of liver damage (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), liver total cholesterol (TC) and triglycerides (TG) contents, and obviously decreased hepatic steatosis score and NAFLD Activity Score (NAS) in the NAFLD mouse model. Western blot results showed that E1231 treatment significantly regulated lipid-metabolism-related protein expression. In particular, E1231 treatment increased SIRT1, PGC-1α, and p-AMPKα protein expression but decreased ACC and SCD-1 protein expression. Additionally, in vitro studies demonstrated that E1231 inhibited lipid accumulation and improved mitochondrial function in free-fatty-acid-challenged hepatocytes, and required SIRT1 activation. In conclusion, this study illustrated that the SIRT1 activator E1231 alleviated HFHC-induced NAFLD development and improved liver injury by regulating the SIRT1-AMPKα pathway, and might be a promising candidate compound for NAFLD treatment.

Construction of a DNA Nanoassembly Based on Spatially Ordered Recognition Elements for Inhibiting ß-Amyloid Aggregation.

A ß-amyloid (Aß) aggregation process is a spontaneous process where the original random coil or helical structure changes into a regularly arranged ß-sheet structure. The development of inhibitors with the features of low cost, high efficiency, and biosafety by targeting Aß self-aggregation is significant for Alzheimer's disease treatment. However, the issues of low inhibition efficiency under low concentrations of inhibitors and biological toxicity are currently to be addressed. To resolve the above problems, a DNA nanoassembly (HCR-Apt) based on spatially ordered recognition elements was constructed by targeted disruption of Aß ordered arrangement. It was discovered that HCR-Apt could inhibit effectively the fibrillation of Aß40 monomers and oligomers at substoichiometric ratios. This may be due to orderly arrangement of aptamers in rigid nanoskeletons for enhancing the recognition interaction between aptamers and Aß40. The strong interaction between HCR-Apt and Aß40 limited the flexible conformational conversion of Aß40 molecules, thereby inhibiting their self-assembly. Computational simulations and experimental analysis revealed the interactions of Apt42 with Aß40, which explained different inhibition effects on the fibrillation of Aß40 monomers and oligomers. Furthermore, the analysis of tyrosine intrinsic fluorescence spectra and surface plasmon resonance imaging showed that the interaction of HCR-Apt and Aß40 was stronger than that of Apt42 and Aß40. These findings contributed to establishing a promising method of boosting the recognition interaction by orderly arrangement of recognition elements. Taken together, this work is expected to provide a simple and efficient strategy for inhibiting Aß aggregation, expanding aptamer's application potential in neurodegenerative diseases.

Effectiveness of preserved vagal nerve in totally laparoscopy radical distal gastrectomy: a matched-paired cohort analysis.

BACKGROUND: The aim of this retrospective matched-paired cohort study was to clarify the effectiveness of preserving the vagus nerve in totally laparoscopic radical distal gastrectomy (TLDG). METHODS: One hundred eighty-three patients with gastric cancer who underwent TLDG between February 2020 and March 2022 were included and followed up. Sixty-one patients with preservation of the vagal nerve (VPG) in the same period were matched (1:2) to conventional sacrificed (CG) cases for demographics, tumor characteristics, and tumor node metastasis stage. The evaluated variables included intraoperative and postoperative indices, symptoms, nutritional status, and gallstone formation at 1 year after gastrectomy between the two groups. RESULTS: Although the operation time was significantly increased in the VPG compared with the CG (198.0 ± 35.2 vs. 176.2 ± 35.2 min, P < 0.001), the mean time of gas passage in the VPG was significantly lower than that in the CG (68.1 ± 21.7 h vs. 75.4 ± 22.6 h, P = 0.038). The overall postoperative complication rate was similar between the two groups (P = 0.794). There was no statistically significant difference between the two groups hospital stay, total number of harvested lymph nodes, and mean number of examined lymph nodes at each station. During follow-up, the morbidity of gallstones or cholecystitis (8.2% vs. 20.5%, P = 0.036), chronic diarrhea (3.3% vs. 14.8%, P = 0.022), and constipation (4.9% vs. 16.4%, P = 0.032) were significantly lower in the VPG than in the CG in this study. Moreover, injury to the vagus nerve was found to be an independent risk factor for gallstone formation or cholecystitis and chronic diarrhea in univariate analysis and multivariate analysis. CONCLUSION: The vagus nerve plays an imperative role in gastrointestinal motility, and hepatic and celiac branch preservation mainly exerts efficacy and safety in patients who undergo TLDG.

To cut or not to cut? A prospective randomized controlled trial on short-term outcomes of the uncut Roux-en-Y reconstruction for gastric cancer.

BACKGROUND: Roux-en-Y (R-Y) anastomoses have been widely used in distal gastrectomy, while the incidence of Roux stasis syndrome remains common. Uncut R-Y anastomosis maintains the neuromuscular continuity, thus avoiding the ectopic pacemaker of the Roux limb and reducing the occurrence of Roux stasis. However, retrospective studies of Uncut R-Y anastomosis remain scarce and randomized controlled trials have not been reported. METHODS: We conducted a randomized controlled trial to compare the surgical safety, nutritional status, and postoperative quality of life (QOL) between uncut and classic Roux-en-Y (R-Y) reconstruction patients. Patients with Stage I gastric cancer were randomly enrolled and underwent laparoscopic distal gastrectomy followed by uncut or classic R-Y reconstruction. Body mass index and blood test were used to evaluate the nutritional status. QOL was evaluated using European Organization for Research and Treatment of Cancer QOL Questionnaire (STO22) and laboratory examinations at postoperative month (POM) 3, 6, 9, and 12. Computed tomography scanning was used to evaluate the skeletal muscle index (SMI) at POM 6 and 12. Endoscopy was performed at POM 12. RESULTS: Operation time, blood loss, time to recovery, complication morbidities, and overall survival were similar between the two groups. Compared with the classic R-Y group, the uncut R-Y group displayed a significantly decreased QOL at POM 9, possibly due to loop recanalization, determined to be occupied 34.2% of the uncut R-Y group. Post-exclusion of recanalization, the QOL was still higher in the classic R-Y group than in the uncut R-Y group, despite their hemoglobin and total protein levels being better than those in the classic R-Y group. Preoperative pre-albumin level and impaired fasting glycemia significantly correlated with the postoperative recanalization. CONCLUSION: We found no significant benefit of uncut over classic R-Y reconstruction which challenges the superiority of the uncut R-Y reconstruction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02644148.

H3K27 acetylation activated-CD109 evokes 5-fluorouracil resistance in gastric cancer via the JNK/MAPK signaling pathway.

Drug resistance is a considerable obstacle to gastric cancer (GC) treatment. The current work aimed to elucidate the functional mechanism of CD109 in 5-fluorouracil (5-FU) resistance in GC. In this study, we demonstrated that CD109 was extremely heightened in 5-FU-resistant GC cells. CD109 deficiency lessened the IC50 value, impaired cell viability and metastatic capability, and induced cell apoptosis after 5-FU treatment in cells. In addition, we found that PAX5 bound p300 increased the enrichment of H3K27ac at the promoter region of the CD109 gene, which resulted in the upregulation of CD109 in GC. Moreover, we also revealed that CD109 triggered 5-FU resistance via activating the JNK/MAPK signaling. Blockage of JNK/MAPK signaling using JNK inhibitor, SP600125, abolished CD109 upregulation-induced changes of IC50 values, cell viability, metastasis and apoptosis in NCI-N87/5-FU and SNU-1/5-FU cells. Importantly, CD109 silencing enhanced the therapeutic efficacy of 5-FU, leading to reduced tumor growth in vivo. In conclusion, our results unveiled that H3K27 acetylation activated-CD109 enhanced 5-FU resistance of GC cells via modulating the JNK/MAPK signaling pathway, which might provide an attractive therapeutic target for GC.

Manipulating Host-Guest Charge Transfer of a Water-Soluble Double-Cavity Cyclophane for NIR-II Photothermal Therapy.

Water-soluble small organic photothermal agents (PTAs) over NIR-II biowindow (1000-1350 nm) are highly desirable, but the rarity greatly limits their applications. Based on a water-soluble double-cavity cyclophane GBox-44+ , we report a class of host-guest charge transfer (CT) complexes as structurally uniform PTAs for NIR-II photothermal therapy. As a result of its high electron-deficiency, GBox-44+ can bind different electron-rich planar guests with a 1 : 2 host/guest stoichiometry to readily tune the CT absorption band that extends to the NIR-II region. When using a diaminofluorene guest substituted with an oligoethylene glycol chain, the host-guest system realized both good biocompatibility and enhanced photothermal conversion at 1064 nm, and was then exploited as a high-efficiency NIR-II PTA for cancer cell and bacterial ablation. This work broadens the potential applications of host-guest cyclophane systems and provides a new access to bio-friendly NIR-II photoabsorbers with well-defined structures.

Screened α-Helix Peptide Inhibitor toward SARS-CoV-2 by Blocking a Prion-like Domain in the Receptor Binding Domain.

A new peptide inhibitor was designed and optimized from an α-helix-rich peptide library specifically toward the critical prion-like domain (PLD) of SARS-CoV-2. It compactly blocked the S1 protein and potently neutralized the pseudovirus which shows promising potential for prophylactic and treatment of COVID-19.

Peptide-Derived Biosensors and Their Applications in Tumor Immunology-Related Detection.

Small-molecular targeting peptides possess features of biocompatibility, affinity, and specificity, which is widely applied in molecular recognition and detection. Moreover, peptides can be developed into highly ordered supramolecular assemblies with boosting binding affinities, diverse functions, and enhanced stabilities suitable for biosensors construction. In this Review, we summarize recent progress of peptide-based biosensors for precise detection, especially on tumor-related analysis, as well as further provide a brief overview of the progress in tumor immune-related detection. Also, we are looking forward to the prospective future of peptide-based biosensors.

Controlled Recognition and Corona Formation by Cascade Micellar Nanoprobes: for Boosting Glioma Theranostics.

Both tumor-cell-targeting and BBB (blood-brain barrier)-penetrating ability are the key characteristics for glioma theranostics. We established one type of nanomicellar probe functionalized with a newly developed peptide WES. The micellar system could enact a series of cascaded functions in living bodies. It could specifically recruit the ApoE corona in blood circulation rather than perform nonspecific protein absorption. Following, it could penetrate into the BBB in an active manner. Finally, and most importantly, it could recognize and target the tumor marker as well as deliver drugs effectively toward glioma. The cascaded micellar system has shown satisfactory therapeutic ability for glioma in both a subcutaneous and orthotopic model, which provides a prospective strategy for brain cancer treatment.

Scintillation index for the optical wave in the vertical oceanic link with anisotropic tilt angle.

The influence of the ocean depth and anisotropic tilt angle on vertical underwater wireless optical communication (UWOC) systems is considered in this study. We propose a power spectrum model of oceanic turbulence with an anisotropic tilt angle for the first time. Thereafter, the expression of the scintillation index is derived for a spherical wave propagating over anisotropic oceanic turbulence in the vertical link. In addition, considering the temperature and salinity, relevant data of the Atlantic and Pacific oceans at different depths are selected to study further the effect of ocean depth on the scintillation index. The results indicate that the scintillation index strongly depends on the ocean depth and anisotropic tilt angle. Moreover, the scintillation index is also related to other parameters, such as temperature and salinity, kinematic viscosity, the anisotropic factor, optical wavelength, and propagation distance. The presented results can be beneficial in designing optical wireless communication systems in the ocean environment.

Optical curvature sensor with high resolution based on in-line fiber Mach-Zehnder interferometer and microwave photonic filter.

Curvature measurement plays an important role in structural health monitoring, robot-pose measuring, etc. High-resolution curvature measurement is highly demanded. In this paper, an optical curvature sensor with high resolution based on in-fiber Mach-Zehnder interferometer (MZI) and microwave photonic filter (MPF) is proposed and experimentally demonstrated. The in-fiber MZI is constructed with a ring-core fiber (RCF) which is fusion spliced between two coreless fibers (CLFs). The structure of CLF-RCF-CLF is then sandwiched between two segments of single-mode fiber (SMF), making the whole interferometer structure of SMF-CLF-RCF-CLF-SMF. The operating principle is that different curvatures will cause the variations of the interference spectrum of MZI due to elastic-optic effect, and then the variations are converted into the frequency-shift of the MPF. The factors affecting the visibility of the interference spectrum are researched. A preliminary exploration of the multiplexing demodulation for the in-fiber-MZIs is also investigated and discussed, which is for the first time to the best of our knowledge, holding great potential to pave the way for constructing the sensing network composed of interferometric sensors. The curvature measurement sensitivity is -147.634 MHz/m-1, and the resolution is 6.774 × 10-6 m-1 which is the highest value up to now.

Quantitative demodulation of distributed low-frequency vibration based on phase-shifted dual-pulse phase-sensitive OTDR with direct detection.

Phase-sensitive optical time-domain reflectometry (Φ-OTDR) has been proposed for distributed vibration sensing purpose over recent years. Emerging applications, including seismic and hydroacoustic wave detection, demand accurate low-frequency vibration reconstruction capability. We propose to use the direct-detection Φ-OTDR configuration to achieve quantitative demodulation of external low-frequency vibrations by phase-shifted dual-pulse probes. Simultaneous pulsing and phase shifting modulation is realized with a single acousto-optic modulator to generate such probes, relaxing the need for an additional optical phase modulator. In the experiments, vibrations with frequency as low as 0.5 Hz are successfully reconstructed with 10 m spatial resolution and 35 dB signal-to-noise ratio. Excellent linearity and repeatability are demonstrated between the optical phase demodulation results and the applied vibration amplitudes. The proposed method is capable of quantitative demodulation of low-frequency vibrations with a cost-effective system configuration and high computation efficiency, showing potential for commercial applications of distributed seismic or hydroacoustic wave acquisition.

Ultra-low sampling resolution technique for heterodyne phase-OTDR based distributed acoustic sensing.

Phase-sensitive optical time-domain reflectometry (Φ-OTDR) based on heterodyne detection is widely used for its simple structure and high signal-to-noise ratio (SNR). However, the large amount of raw data of Φ-OTDR places a heavy burden on the storage device and also limits the transferability of the data. In this Letter, we propose an ultra-low sampling resolution technique to solve the data storage problem in heterodyne Φ-OTDR. Experimental results show that the optical phase variations induced by external vibrations can be successfully demodulated from the 1-bit-resolution raw data, and a vibration SNR of 58.03 dB is achieved. In addition, this work also reveals that a data acquisition device with extremely low sampling resolution is sufficient for heterodyne Φ-OTDR, signifying that the cost of the system can be further decreased.

Efficacy and safety of miconazole muco-adhesive tablet versus itraconazole in oropharyngeal candidiasis: A randomized, multi-centered, double-blind, phase 3 trial.

Oropharyngeal candidiasis (OPC) is an opportunistic infection treated with anti-fungal agents. Herein, we evaluate the efficacy and safety of miconazole buccal tablets (MBT) and itraconazole capsules in the localized treatment of patients with OPC. In this multi-centered, double-blinded, phase III trial (CTR20130414), both males and non-pregnant females (≥18 years) with OPC were randomized (1:1) to MBT plus placebo (experimental group) or itraconazole capsules plus placebo (control group). The primary endpoint was clinical cure at the end-of-treatment period [visit 4 (V4)] while secondary endpoints were clinical remission rates, partial remission rates, mycological cure, clinical relapse, and adverse events (AEs). All endpoints were statistically analyzed in both the full analysis set (FAS) and per-protocol (PP) set. A total of 431 (experimental: 216; control: 215) subjects were included. At V4, in the FAS set, the clinical cure was achieved in 68% and 59% patients in experimental and control groups, respectively with a treatment difference of 9% [95% confidence interval (CI): -1,19; P < .001] demonstrating non-inferiority of MBT over itraconazole. At V4, mycological cure rates were 68.2% and 42.0% in the experimental group and control groups (P < .001), respectively in FAS. The relapse rates were 5.4% and 6.6%, respectively, in the experimental and control groups. A total of 210 patients experienced AEs during treatment with 47.7% in the experimental group and 49.8% in the control group with no deaths. This study demonstrated that once-daily treatment with MBT was non-inferior to itraconazole with higher mycological cure rates and was tolerable with mild AE in patients with OPC.

Miconazole is an antifungal drug against certain types of fungus or yeast infections. In this study, we showed that treatment with once-daily miconazole buccal tablets was as effective as systemic itraconazole capsules in Chinese patients infected by oropharyngeal candidiasis with minimum side effects.

Real-Time Multi-Class Disturbance Detection for Φ-OTDR Based on YOLO Algorithm.

This paper proposes a real-time multi-class disturbance detection algorithm based on YOLO for distributed fiber vibration sensing. The algorithm achieves real-time detection of event location and classification on external intrusions sensed by distributed optical fiber sensing system (DOFS) based on phase-sensitive optical time-domain reflectometry (Φ-OTDR). We conducted data collection under perimeter security scenarios and acquired five types of events with a total of 5787 samples. The data is used as a spatial-temporal sensing image in the training of our proposed YOLO-based model (You Only Look Once-based method). Our scheme uses the Darknet53 network to simplify the traditional two-step object detection into a one-step process, using one network structure for both event localization and classification, thus improving the detection speed to achieve real-time operation. Compared with the traditional Fast-RCNN (Fast Region-CNN) and Faster-RCNN (Faster Region-CNN) algorithms, our scheme can achieve 22.83 frames per second (FPS) while maintaining high accuracy (96.14%), which is 44.90 times faster than Fast-RCNN and 3.79 times faster than Faster-RCNN. It achieves real-time operation for locating and classifying intrusion events with continuously recorded sensing data. Experimental results have demonstrated that this scheme provides a solution to real-time, multi-class external intrusion events detection and classification for the Φ-OTDR-based DOFS in practical applications.