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Chemical upcycling of waste polyethylene terephthalate (PET) to value-added products can reduce the emission of CO 2 , microplastics and toxic chemicals. In this work, mesoporous H-type Zeolite Socony Mobil-5 (HZSM-5) supported Ru catalyst (Ru/m-HZSM-5) was synthesized and tested in the hydrogenation of PET degraded chemicals (bis(2-hydroxyethyl) terephthalate, dimethyl terephthalate, diethyl terephthalate, and terephthalic acid). Characterizations disclosed that Ru/m-HZSM-5 catalyst possesses mesopores (a dominant channel of 5.32 nm), enlarged specific surface area (404 m 2 ·g -1 ), and Ru NPs dispersed highly (40.6 %) compared to that of Ru/HZSM-5. And also, it was found that Ru/m-HZSM-5 was capable for the hydrogenation of benzene rings in these PET degraded chemicals with large sizes (1.09-1.82 nm). In particular, the conversion of BHET and the selectivity of BHCD over Ru/m-HZSM-5 reached 95.5 % and 95.6 % at 120 °C within 2 h. And Ru/m-HZSM-5 could be recycled at least five times without obvious loss of activity and selectivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study describes the synthesis and characterization of a novel near-infrared (NIR) fluorescent probe RBNE based on a hybrid rhodamine dye, which shows excellent optical capability for detecting and imaging ONOO - in necrotizing enterocolitis (NEC) mouse model. The probe RBNE undergoes hydrazine redox-process, and subsequently the spirocyclic structure's opening, resulting in a turn-on fluorescence emission with the presence of ONOO - , which exhibits several excellent features, including a significant Stokes shift of 108 nm, near-infrared emission at 668 nm, a lower detection limit of 56 nM, low cytotoxicity, and excellent imaging ability for ONOO - both in vitro and in vivo. The presented study introduces a novel optical tool that has the potential to significantly advance our understanding of peroxynitrite (ONOO - ) behaviors in necrotizing enterocolitis (NEC)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Dissatisfaction after total knee arthroplasty (TKA) ranges from 15 to 30%. While patient selection may be partially responsible, morphological and reconstructive challenges may be determinants. Preoperative computed tomography (CT) scans for TKA planning allow us to evaluate the hip-knee-ankle axis and establish a baseline phenotypic distribution across anatomic parameters. The purpose of this cross-sectional analysis was to establish the distributions of 27 parameters in a pre-TKA cohort and perform threshold analysis to identify anatomic outliers., Methods: There were 1,352 pre-TKA CTs that were processed. A 2-step deep learning pipeline of classification and segmentation models identified landmark images and then generated contour representations. We used an open-source computer vision library to compute measurements for 27 anatomic metrics along the hip-knee axis. Normative distribution plots were established, and thresholds for the 15th percentile at both extremes were calculated. Metrics falling outside the central 70th percentile were considered outlier indices. A threshold analysis of outlier indices against the proportion of the cohort was performed., Results: Significant variation exists in pre-TKA anatomy across 27 normally distributed metrics. Threshold analysis revealed a sigmoid function with a critical point at 9 outlier indices, representing 31.2% of subjects as anatomic outliers. Metrics with the greatest variation related to deformity (tibiofemoral angle, medial proximal tibial angle, lateral distal femoral angle), bony size (tibial width, anteroposterior femoral size, femoral head size, medial femoral condyle size), intraoperative landmarks (posterior tibial slope, transepicondylar and posterior condylar axes), and neglected rotational considerations (acetabular and femoral version, femoral torsion)., Conclusions: In the largest non-industry database of pre-TKA CTs using a fully automated 3-stage deep learning and computer vision-based pipeline, marked anatomic variation exists. In the pursuit of understanding the dissatisfaction rate after TKA, acknowledging that 31% of patients represent anatomic outliers may help us better achieve anatomically personalized TKA, with or without adjunctive technology., (Copyright © 2024 Elsevier Inc. All rights reserved.)

One-for-all phototheranostics based on a single molecule is recognized as a convenient approach for cancer treatment, whose efficacy relies on precise lesion localization through multimodal imaging, coupled with the efficient exertion of phototherapy. To unleash the full potential of phototheranostics, advancement in both phototheranostic agents and light delivery methods is essential. Herein, an integrated strategy combining a versatile molecule featuring aggregation-induced emission, namely tBuTTBD, with a modified optical fiber to realize comprehensive tumor diagnosis and "inside-out" irradiation in the orthotopic breast tumor, is proposed for the first time. Attributed to the intense donor-acceptor interaction, highly distorted conformation, abundant molecular rotors, and loose intermolecular packing upon aggregation, tBuTTBD can synchronously undergo second near-infrared (NIR-II) fluorescence emission, photothermal and photodynamic generation under laser irradiation, contributing to a trimodal NIR-II fluorescence-photoacoustic (PA)-photothermal imaging-guided phototherapy. The tumor treatment is further carried out following the insertion of a modified optical fiber, which is fabricated by splicing a flat-end fiber with an air-core fiber. This configuration aims to enable effective in situ phototherapy by maximizing energy utilization for therapeutic benefits. This work not only enriches the palette of NIR-II phototheranostic agents but also provides valuable insight for exploring an integrated phototheranostic protocol for practical cancer treatment., (© 2024 Wiley‐VCH GmbH.)

The high disease burden of influenza virus poses a significant threat to human health. Optimized diagnostic technologies that combine speed, sensitivity, and specificity with minimal equipment requirements are urgently needed to detect the many circulating species, subtypes, and variants of influenza at the point of need. Here, we introduce such a method using Streamlined Highlighting of Infections to Navigate Epidemics (SHINE), a clustered regularly interspaced short palindromic repeats (CRISPR)-based RNA detection platform. Four SHINE assays were designed and validated for the detection and differentiation of clinically relevant influenza species (A and B) and subtypes (H1N1 and H3N2). When tested on clinical samples, these optimized assays achieved 100% concordance with quantitative RT-PCR. Duplex Cas12a/Cas13a SHINE assays were also developed to detect two targets simultaneously. This study demonstrates the utility of this duplex assay in discriminating two alleles of an oseltamivir resistance (H275Y) mutation as well as in simultaneously detecting influenza A and human RNAse P in patient samples. These assays have the potential to expand influenza detection outside of clinical laboratories for enhanced influenza diagnosis and surveillance., Competing Interests: Disclosure Statement J.A.-S., P.C.S., and C.M. are inventors on a pending patent application held by the Broad Institute (international patent application number PCT/US2021/049145), which covers the SHINE technology. P.C.S. is a cofounder of, shareholder in, and consultant to Sherlock Biosciences, Inc., and Delve Bio, as well as a board member of and shareholder in Danaher Corp. C.M. is a cofounder of Carver Biosciences, a startup company developing Cas13-based antivirals, and holds equity in Carver Biosciences., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

This study investigated the potential ability of the fluorescent probe Ly-CHO to detect formaldehyde (FA) in living cells and tumor-bearing mice. Ly-CHO exhibited great selectivity, excellent sensitivity, and rapid response to FA, making it a valuable tool for tracking FA concentration changes. The probe was also found to target lysosomes specifically. Furthermore, Ly-CHO showed an obvious fluorescence increase in endogenous CHO detection after adding tetrahydrogen folic acid (THFA). This study validated Ly-CHO's possibility for FA imaging in vivo, with potential applications in understanding formaldehyde-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Variability in the bony morphology of pathologic hips/knees is a challenge in automating preoperative computed tomography (CT) scan measurements. With the increasing prevalence of CT for advanced preoperative planning, processing this data represents a critical bottleneck in presurgical planning, research, and development. The purpose of this study was to demonstrate a reproducible and scalable methodology for analyzing CT-based anatomy to process hip and knee anatomy for perioperative planning and execution., Methods: One hundred patients with preoperative CT scans undergoing total knee arthroplasty for osteoarthritis were processed. A two-step deep learning pipeline of classification and segmentation models was developed that identifies landmark images and then generates contour representations. We utilized an open-source computer vision library to compute measurements. Classification models were assessed by accuracy, precision, and recall. Segmentation models were evaluated using dice and mean Intersection over Union (IOU) metrics. Contour measurements were compared against manual measurements to validate posterior condylar axis angle, sulcus angle, trochlear groove-tibial tuberosity distance, acetabular anteversion, and femoral version., Results: Classifiers identified landmark images with accuracy of 0.91 and 0.88 for hip and knee models, respectively. Segmentation models demonstrated mean IOU scores above 0.95 with the highest dice coefficient of 0.957 [0.954-0.961] (UNet3+) and the highest mean IOU of 0.965 [0.961-0.969] (Attention U-Net). There were no statistically significant differences for the measurements taken automatically vs manually ( P > 0.05). Average time for the pipeline to preprocess (48.65 +/- 4.41 sec), classify/retrieve landmark images (8.36 +/- 3.40 sec), segment images (<1 sec), and obtain measurements was 2.58 (+/- 1.92) minutes., Conclusions: A fully automated three-stage deep learning and computer vision-based pipeline of classification and segmentation models accurately localized, segmented, and measured landmark hip and knee images for patients undergoing total knee arthroplasty. Incorporation of clinical parameters, like patient-reported outcome measures and instability risk, will be important considerations alongside anatomic parameters., (© 2024 The Authors.)

In this study, we present a novel near-infrared (NIR) fluorescent probe Nile-ONO designed for the selective and sensitive detection of ONOO - . The probe Nile-ONO employed Nile red as the fluorophore, with diphenylphosphinate serving as the reaction site. In the presence of ONOO - , the probe Nile-ONO exhibits remarkable fluorescence enhancement at 659 nm, with a response time of less than 20 min and a low detection limit of 0.32 µM. Importantly, MTT assays demonstrate low cytotoxicity in living cells. Furthermore, Nile-ONO has excellent imaging capabilities for endogenous ONOO - . Overall, this work introduces a valuable new method for the rapid detection of ONOO - in biological systems., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Identification of protein profiling on plasma exosomes by SERS can be a promising strategy for early cancer diagnosis. However, it is still challenging to detect multiple exosomal proteins simultaneously by SERS since the Raman signals of exosomes detected by conventional colloidal nanocrystals or two-dimensional SERS substrates are incomplete and complex. Herein, we develop a novel three-dimensional (3D) surround-enhancing SERS platform, named 3D se-SERS, for the multiplex detection of exosomal proteins. In this 3D se-SERS, proteins and exosomes are covered with "hotspots" generated by the gold nanoparticles, which surround the analytes densely and three-dimensionally, providing sensitive and comprehensive SERS signals. Combining this 3D se-SERS with a deep learning model, we successfully quantitatively profiled seven proteins including CD63, CD81, CD9, CD151, CD171, TSPAN8, and PD-L1 on the surface of plasma exosomes from patients, which can predict the occurrence and advancement of lung cancer. This 3D se-SERS integrating deep learning technique benefits from high sensitivity and significant multiplexing ability for comprehensive analysis of proteins and exosomes, demonstrating the potential of deep learning-driven 3D se-SERS technology for plasma exosome-based early cancer diagnosis.

Femtosecond laser electronic excitation tagging (FLEET) velocimetry is an important diagnostic technique for seedless velocimetry measurements particularly in supersonic and hypersonic flows. Typical FLEET measurements feature a single laser line and camera system to achieve one-component velocimetry along a line, although some multiple-spot and multiple-component configurations have been demonstrated. In this work, tomographic imaging is used to track the three-dimensional location of many FLEET spots. A quadscope is used to combine four unique views onto a single high-speed image intensifier and camera. Tomographic reconstructions of the FLEET emission are analyzed for three-component velocimetry from multiple FLEET spots. Glass wedges are used to create many (nine) closely spaced FLEET spots with less than 10% transmission losses. These developments lead to a significant improvement in the dimensionality and spatial coverage of a FLEET instrument with some increases in experimental complexity and data processing. Multiple-point three-component FLEET velocimetry is demonstrated in an underexpanded jet.

Objective: To screen the risk factors affecting the recurrence risk of patients with ampullary carcinoma (AC)after radical resection, and then to construct a model for risk prediction based on Lasso-Cox regression and visualize it., Methods: Clinical data were collected from 162 patients that received pancreaticoduodenectomy treatment in Hebei Provincial Cancer Hospital from January 2011 to January 2022. Lasso regression was used in the training group to screen the risk factors for recurrence. The Lasso-Cox regression and Random Survival Forest (RSF) models were compared using Delong test to determine the optimum model based on the risk factors. Finally, the selected model was validated using clinical data from the validation group., Results: The patients were split into two groups, with a 7:3 ratio for training and validation. The variables screened by Lasso regression, such as CA19-9/GGT, AJCC 8th edition TNM staging, Lymph node invasion, Differentiation, Tumor size, CA19-9, Gender, GPR, PLR, Drinking history, and Complications, were used in modeling with the Lasso-Cox regression model (C-index = 0.845) and RSF model (C-index = 0.719) in the training group. According to the Delong test we chose the Lasso-Cox regression model (P = 0.019) and validated its performance with time-dependent receiver operating characteristics curves(tdROC), calibration curves, and decision curve analysis (DCA). The areas under the tdROC curves for 1, 3, and 5 years were 0.855, 0.888, and 0.924 in the training group and 0.841, 0.871, and 0.901 in the validation group, respectively. The calibration curves performed well, as well as the DCA showed higher net returns and a broader range of threshold probabilities using the predictive model. A nomogram visualization is used to display the results of the selected model., Conclusion: The study established a nomogram based on the Lasso-Cox regression model for predicting recurrence in AC patients. Compared to a nomogram built via other methods, this one is more robust and accurate., (© 2024. The Author(s).)

Many pathological processes include nitric oxide (NO), a signaling transduction molecule. Tumors, cardiovascular, cerebrovascular, neurodegenerative, and other illnesses are linked to abnormal NO levels. Thus, evaluating NO levels in vitro and in vivo is crucial for studying chemical biology process of associated disorders. This work devised and manufactured a coumarin-based fluorescent probe ZPS-NO to detect nitric oxide (NO). The reaction between ZPS-NO and NO produced a highly selective and sensitive optical response that caused a powerful fluorescence "turn-on" effect with a ultra-low NO detection limit of 14.5 nM. Furthermore, the probe was applied to sense and image NO in living cells and inflammatory model of zebrafish, as well as to detect NO in periodontitis patients' saliva samples. We anticipate that probe ZPS-NO will serve as a practical and effective tool for assessing the interactions and evaluation of periodontitis development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The noise associated with ceramic-on-ceramic (CoC) total hip arthroplasty (THA) has been a concerning issue, while its underlying causes remain unclear., Methods: We conducted a retrospective analysis of 119 patients (174 primary CoC THAs) who had a mean follow-up of 28 months (range, 12 to 106). A questionnaire was designed to collect information on nature, frequency, onset, duration, and impact of the noise. Postoperative x-rays were evaluated. Clinical evaluations, including Harris and Oxford hip scores, were documented at follow-up time points (6 weeks, 3 months, 6 months, and 1 year)., Results: Of the 174 hips, 31.6% reported noise, including 26 popping (14.9%), 24 clicking (12.1%), and 5 grinding (2.9%). No patients reported squeaking. Noisy hips had lower age (P = .009) and body mass index (P = .019). Among patients with developmental dysplasia of the hip, 17 of 55 hips reported noise associated with smaller cup anteversion angle (P = .004), greater body height (P = .022), and larger acetabular cup size (P = .049). Noise typically began at a mean of 193 days (range, 1 to 2,598) after surgery and disappeared spontaneously in 50.9% of hips before final follow-up, with an average disappearance time of 211 days (range, 60 to 730). Noise did not affect daily life in 74.5% of patients, while 26.9% of patients who had popping reported painful sensations. One patient experienced joint dislocation, and another experienced a ceramic liner fracture during follow-up. No statistical difference was observed in outcome scores between noise and silent groups at 4 follow-up time points., Conclusions: Incidence of noise after primary CoC THA is relatively high. Smaller cup anteversion and larger acetabular cup size were associated with noise production in patients who had developmental dysplasia of the hip., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mercury sensing and imaging in the bio-system is essential for comprehending its toxicity and therapies. Based on the merocyanine scaffold, we designed and synthesized two novel near-infrared (NIR) fluorescent probes for detecting Hg 2+ . The release of chloro-substituted merocyanine structure on the probe CyHg-Cl enables fluorescence enhancement rapidly by introducing Hg 2+ . In addition, the probe CyHg-Cl exhibits NIR emission and a low detection limit of 0.59 µM. Finally, the probe CyHg-Cl was used to detect Hg 2+ in live cells and real water samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Developing advanced sensing technologies for phosgene is critical for public safety and national security. Here, we report a novel fluorescent probe NP (abbreviation for naphthalimide-based probe) for the selective detection of phosgene. The sensor was synthesized through a substitution reaction between 1,8-naphthalimide with 1,4,7-triazacyclononane. The high reactivity of probe NP towards phosgene led to a marked fluorescence emission turn-on, demonstrating the high selectivity of this sensor. Furthermore, a practical on-site detection method for phosgene was developed by loading probe NP on test strips. These test strips can detect gaseous phosgene below 1 ppm. The successful development of this sensor opens up new possibilities for detecting methods for phosgene., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023. Published by Elsevier B.V.)

Aim: The aim of this review was to determine the effectiveness of the e-learning programs for improving the knowledge and professional practices of nursing personnel in managing pressure injuries patients., Design: Systematic review and meta-analysis., Methods: Systematic search was done in EMBASE, SCOPUS, Cochrane library, MEDLINE, Google Scholar, ScienceDirect and Clinicaltrials.gov databases until August 2022. Meta-analysis was carried out using random-effects model, and the results were reported as pooled standardized mean differences (SMD), or odds ratios (OR) with 95% confidence intervals (CIs)., Results: Eight studies were included in the analysis. Most of the studies had higher risk of bias. The pooled SMD for knowledge score and for the classification skill were 1.40 (95%CI: 0.45-2.35; I 2  = 93.1%) and 1.75 (95%CI: 0.94-3.24; I 2  = 78.3%) respectively. The pooled OR for the classification skills was 1.75 (95%CI: 0.94-3.24; I 2  = 78.3%)., Patient or Public Contribution: No patient or public contribution., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Visualization of photothermal therapy mediated by photothermal transduction agents (PTAs) is important to promote individual treatment of patients with low side effects. Photoacoustic detection has emerged as a promising noninvasive method for the visualization of PTAs distribution but still has limitations in temperature measurement, including poor measurement accuracy and low tissue penetration depth. In this study, we developed biocompatible semiconducting polymer dots (SPD) for in situ coupling of photothermal and photoacoustic detection in the near-infrared II window. SPD has dual photostability under pulsed laser and continuous-wave laser irradiation with a photothermal conversion efficiency of 42.77%. Meanwhile, a strong correlation between the photoacoustic signal and the actual temperature of SPD can be observed. The standard deviation of SPD-mediated photoacoustic thermometry can reach 0.13 °C when the penetration depth of gelatin phantom is 9.49 mm. Preliminary experimental results in vivo show that SPD-mediated photoacoustic signal has a high signal-to-noise ratio, as well as good performance in temperature response and tumor enrichment. Such a study not only offers a new nanomaterial for the visualization of photothermal therapy but will also promote the theranostic platform for clinical applications., (© 2023. The Author(s).)

This study aimed to predict the outcome of patient specific quality assurance (PSQA) in IMRT for breast cancer using complexity metrics, such as MU factor, MAD, CAS, MCS. Several breast cancer plans were considered, including LBCS, RBCS, LBCM, RBCM, left breast, right breast and the whole breast for both Edge and TrueBeam LINACS. Dose verification was completed by Portal Dosimetry (PD). The receiver operating characteristic (ROC) curve was employed to determine whether the treatment plans pass or failed. The area under the curve (AUC) was used to assess the classification performance. The correlation of PSQA and complexity metrics was examined using Spearman's rank correlation coefficient (R s ). For LINACS, the most suitable complexity metric was found to be the MU factor (Edge R s  = - 0.608, p < 0.01; TrueBeam R s  = - 0.739, p < 0.01). Regarding the specific breast cancer categories, the optimal complexity metrics were as follows: MAD (AUC = 0.917) for LBCS, MCS (AUC = 0.681) for RBCS, MU factor (AUC = 0.854) for LBCM and MAD (AUC = 0.731) for RBCM. On the Edge LINAC, the preferable method for breast cancers was MCS (left breast, AUC = 0.938; right breast, AUC = 0.813), while on the TrueBeam LINAC, it became MU factor (left breast, AUC = 0.950) and MCS (right breast, AUC = 0.806), respectively. Overall, there was no universally suitable complexity metric for all types of breast cancers. The choice of complexity metric depended on different cancer types, locations and treatment LINACs. Therefore, when utilizing complexity metrics to predict PSQA outcomes in IMRT for breast cancer, it was essential to select the appropriate metric based on the specific circumstances and characteristics of the treatment., (© 2023. The Author(s).)

Crash prediction models (CPMs) are mostly developed using statistical or data-driven methods that rely on observed crashes. However, the historical crash records can be unreliable due to availability and data quality issues. Near-crashes based CPMs offer a proactive approach to predict crash frequencies prior to the occurrence of crashes. Surrogate safety measures can be used to identify near-crashes from road user trajectories. Roadside LiDAR offers an innovative approach to collect vehicle trajectory data at a microscopic resolution with high accuracy providing detailed information of all road user movements. This study presents a methodology to identify near-crashes from Roadside LiDAR based vehicle trajectory data using the surrogate indicators: TTC (Time to Collision), PET (Post Encroachment Time), ACT (Anticipated Collision Time) and MaxD (Maximum Deceleration). Additionally, time-based, and evasive-action-based surrogate measures are combined as different pairs to obtain crash probabilities using extreme value theory (EVT). The study results show that the bivariate EVT model displays a better fit to conflict extremes, predicting crash frequencies better than the univariate model. Likewise, while the bivariate model with ACT and MaxD pair performed the best in terms of accuracy, the TTC and MaxD pair was able to reflect the relative threat levels at the study intersections. Overall, the methodology lays ground for using roadside lidar based trajectory data for proactive safety analysis of signalized intersections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Luminogens with aggregation-induced emission characteristics (AIEgens) are considered good options for two-photon (2P) probes, owing to their flexibility of design, heavy-metal-free composition, and resistance to photobleaching. However, the design principles for large 2P absorption cross-section (δ) generally require high coplanarity, strong donor-acceptor (D-A) interactions, and long conjugation, which can severely weaken the brightness of AIEgens at the aggregated state and undermine their potential in 2P fluorescence imaging (2PFI). Exploration of a feasible approach to overcome the "Buckets Effect" of AIEgen-based 2P probes is thus a fascinating yet challenging task. Herein, an AIEgen, namely (Z)-2-(4-aminophenyl)-3-(5-(4-(bis(4-methoxyphenyl)amino)phenyl)thiophen-2-yl)acrylonitrile (MTAA) is designed to have a big δ according to the calculation result and a low fluorescence quantum yield (QY) of 2.2% in dimethyl sulfoxide (DMSO). Impressively, upon integrating into bovine serum albumin (BSA), the protein-sized MTAA@BSA dots exhibit a 25-fold higher fluorescence QY compared to MTAA molecules, contributing to an imaging depth of 818 µm in the brain vasculature. The retention and clearance of MTAA@BSA dots in the liver and kidney are also studied using 2PFI. Overall, this work provides a facile approach to overcome the "Buckets Effect" of AIEgen to generate highly efficient, reliable, and biocompatible 2P probes., (© 2023 Wiley-VCH GmbH.)

The CRISPR/Cas13a system has promising applications in clinical small noncoding RNA (sncRNA) detection because it is free from the interference of genomic DNA. However, detecting ultrashort sncRNAs (less than 20 nucleotides) has been challenging because the Cas13a nuclease requires longer crRNA-target RNA hybrids to be activated. Here, we report the development of a foldback-crRNA-enhanced CRISPR/Cas13a (FCECas13a) system that overcomes the limitations of the current CRISPR/Cas13a system in detecting ultrashort sncRNAs. The FCECas13a system employs a 3'-terminal foldback crRNA that hybridizes with the target ultrashort sncRNA, forming a double strand that "tricks" the Cas13a nuclease into activating the HEPN structural domain and generating trans -cleavage activity. The FCECas13a system can accurately detect miRNA720 (a sncRNA currently known as tRNA-derived small RNA), which is only 17 nucleotides long and has a concentration as low as 15 fM within 20 min. This FCECas13a system opens new avenues for ultrashort sncRNA detection with significant implications for basic biological research, disease prognosis, and molecular diagnosis.

Mitochondria, as an energy-producing powerhouse in live cells, is considered to be directly linked to cellular health. However, dysfunctional mitochondria and abnormal mitochondria pH would possibly activate mitophagy, cell apoptosis and intercellular acidification process. In this work, we synthesized a novel near infrared fluorescent probe (FNIR-pH) for measurement of mitochondrial pH based on the hemicyanine skeleton as a fluorophore. The FNIR-pH probe functioned as a mitochondrial pH substrate and exhibited quick and sensitive turn-on fluorescence responses to mitochondrial pH in basic solution due to the deprotonation of hydroxy group in the structure. From pH 3.0 to 10.0, the FNIR-pH exhibited almost 100-fold increase in fluorescence intensity at 766 nm wavelength. The FNIR-pH also displayed superior selectivity to various metal ions, excellent photostability, and low cytotoxicity, which facilitated further biological application. Owing to the proper pKa value of 7.2, the FNIR-pH paved the way for real-time monitoring of mitochondria pH changes in live cells and sensitive sensing of mitophagy. Moreover, the FNIR-pH probe was also implemented for fluorescent imaging of tumor-bearing mice to validate its potential application for in vivo imaging of bioanalytes and biomarkers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Iron plays an important role in neuronal injury and edema formation after intracranial hemorrhage. However, the role of serum iron in aneurysmal subarachnoid hemorrhage (aSAH) is yet to be well-established. This study aims to identify whether serum iron could predict postoperative global cerebral edema (GCE) and poor outcome in aSAH., Methods: 847 patients' aSAH clinical data were retrospectively collected at the First Affiliated Hospital of Fujian Medical University. Data on demographics, clinical characteristics, and laboratory values were collected and analyzed through univariate and multivariate analyses. Propensity score matching (PSM) analysis was performed to balance the baseline differences between the groups., Results: The incidence of high-grade global cerebral edema (H-GCE) following aSAH was 12.99% (110/847). Serum iron levels [odds ratio (OR) = 1.143; 95% confidence interval (CI), (1.097-1.191); p < 0.001] were associated with the occurrence of H-GCE following aSAH in the univariate analysis. This association remained statistically significant even after adjusting for other variables in the multivariate model, with serum iron having an OR of 1.091 (95% CI, 1.043-1.141; p < 0.001) for GCE. After 1:1 PSM, serum iron levels ≤ 10.7 µmol/L remained a significant independent predictor of GCE ( p = 0.002). The receiver operating characteristic (ROC) curve analysis determined that a serum iron cut-off value of ≤ 10.7 µmol/L was optimal for predicting H-GCE [Areas under the ROC curves (AUC) = 0.701, 95% CI, (0.669-0.732), p < 0.001; sensitivity, 67.27%; specificity, 63.77%] in patients with aSAH. Additionally, a trend was observed in which higher Hunt-Hess grades (HH grade) were associated with lower serum iron levels, and higher modified Fisher grades (mFisher grade) were associated with lower serum iron levels. In addition, the serum iron level was also associated with a 3-month functional neurological outcome ( p < 0.001)., Conclusions: The results of this study indicate that a decreased serum iron level serves as a clinically significant biomarker for the prediction of postoperative GCE and a poor outcome at 3-months in patients with aSAH.

DNA aptamers are single-stranded DNA oligonucleotide sequences that bind to specific targets with high affinity. Currently, DNA aptamers can be produced only by in vitro synthesis. It is difficult for DNA aptamers to have a sustained impact on intracellular protein activity, which limits their clinical application. In this study, we developed a DNA aptamer expression system to generate DNA aptamers with functional activity in mammalian cells by mimicking retroviruses. Using this system, DNA aptamers targeting intracellular Ras (Ra1) and membrane-bound CD71 (XQ2) were successfully generated in cells. In particular, the expressed Ra1 not only specifically bound to the intracellular Ras protein but also inhibited the phosphorylation of downstream ERK1/2 and AKT. Furthermore, by inserting the DNA aptamer expression system for Ra1 into a lentivirus vector, the system can be delivered into cells and stably produce Ra1 over time, resulting in the inhibition of lung cancer cell proliferation. Therefore, our study provides a novel strategy for the intracellular generation of DNA aptamers with functional activity and opens a new avenue for the clinical application of intracellular DNA aptamers in disease treatment.

Objective: Effects of Qishen Dihuang (QSDH) granules on intestinal flora of an experimental autoimmune myasthenia gravis (EAMG) model rat were investigated (CNBI:PRJNA910532)., Methods: Thirty-six female Lewis rats were assigned to Control, EAMG, QSDH-low-dose, QSDH-medium-dose, QSDH-high-dose, and Prednisone groups using the random number table method (6 rats/group). A rat EAMG model was established by injecting Rα97-116 peptide antigen. Each day for 30 days, gavages were administered to rats in the Chinese medicine group (QSDH granules in different concentrations), Prednisone group (prednisone), and Control and Model groups (0.5% CMC). After 30-day gavages, rat fecal samples were collected and the microbial community composition and diversity differences between intestinal microbiota of EAMG and QSDH granule-treated groups were analyzed using 16S amplicon sequencing to explore the effect underlying QSDH granules alleviation of EAMG., Results: The clinical symptoms of rats in each treatment group improved significantly after the intervention treatment with QSDH granules. Comparison of the relative abundance of microorganisms in the gut flora of different groups with that of the EAMG group rats revealed: significantly lower phylum-level Bacteroidetes abundance and significantly greater Actinobacteria abundance in the QSDH-high-dose group and a significantly greater Firmicutes/Bacteroidetes ratio in the QSDH-medium-dose group; significantly increased family-level QSDH-high-dose group abundances of Lachnospiraceae and Trichospiraceae (Firmicutes), significantly increased QSDH-medium-dose group Lactobacillaceae abundance, and significantly increased QSDH-low-dose group Bacteroidaceae abundance; genus-level, QSDH-high-dose group Prevotella and Coprococcus abundances were significantly increased and Turicibacter and Lactobacillus abundances were significantly decreased, while QSDH-medium-dose group Akkermansia and Lactobacillus abundances were significantly increased. Greater overall community richness, diversity, and genetic diversity were observed in QSDH granules-treated groups, but differences were insignificant (P > .05). The most significant inter-group genus-level community marker differences involved Prevotella, Ruminococcus, Coprococcus, and Turicibacter., Conclusion: QSDH granules may regulate EAMG rat intestinal flora by decreasing relative abundances of Turicibacter and Clostridium and increasing relative abundances of Bifidobacterium, Lachnospiraceae, and Prevotella.

Compressing high-energy laser pulses to a single-cycle and realizing the "λ 3 laser concept", where λ is the wavelength of the laser, will break the current limitation of super-scale projects and contribute to the future 100-petawatt and even Exawatt lasers. Here, we have realized ultra-broadband gold gratings, core optics in the chirped pulse amplification, in the 750-1150 nm spectral range with a > 90% -1 order diffraction efficiency for near single-cycle pulse stretching and compression. The grating is also compatible with azimuthal angles from -15° to 15°, making it possible to design a three-dimensional compressor. In developing and manufacturing processes, a crucial grating profile with large base width and sharp ridge is carefully optimized and controlled to dramatically broaden the high diffraction efficiency bandwidth from the current 100-200 nm to over 400 nm. This work has removed a key obstacle to achieving the near single-cycle 100-PW lasers in the future., (© 2023. The Author(s).)

Klebsiella pneumoniae is a widespread pathogen of several human diseases. The emergence of multidrug-resistant K. pneumoniae makes the treatment of these diseases a significant challenge. The application of bacteriophages is a potential approach for dealing with the emergence of multidrug-resistant pathogenic bacteria. This study isolates a novel bacteriophage vB&#95;KleM&#95;KB2 that infects the multidrug-resistant clinical isolates of K. pneumoniae. The bacteriophage exhibits a short latent period of 10 min, and can effectively lyse the bacterium within 60 min. Notably, the bacteriophage can completely inhibit the growth of the host bacterium at the initial concentration of 10 7  CFU/mL with a low multiplicity of infection of 0.001, which proves its high lytic activity. Furthermore, the bacteriophage shows high environmental tolerances, which can facilitate the practical application of the bacteriophage. Analysis of the bacteriophage genome shows that the bacteriophage possesses a novel genome sequence and can represent a new bacteriophage genus. Considering the high lytic activity, short latent period, high stability, and novel genetic background, bacteriophage vB&#95;KleM&#95;KB2 enriches the bacteriophage library and provides a new alternative for controlling the diseases caused by multidrug-resistant pathogenic K. pneumoniae., (© 2023. The Author(s).)

Wheat yield has been constrained by stripe rust disease globally. A wheat landrace (Qishanmai, QSM) consistently showed lower stripe rust severities in multiple year studies than susceptible check varieties including Suwon11 (SW) at the adult plant stage. To detect QTL for reducing the severity in QSM, 1218 recombinant inbred lines (RILs) were developed from SW × QSM. QTL detection was conducted firstly using 112 RILs selected for similarity in pheno-morphological characters. The 112 RILs were assessed for stripe rust severity at the 2nd leaf, 6th leaf and flag leaf stages under field and greenhouse conditions, and genotyping was done primarily with a single nucleotide polymorphism (SNP) array. On the basis of these phenotypic and genotypic data, a major QTL ( QYr.cau-1DL ) was detected on chromosome 1D at the 6th leaf and flag leaf stages. Further mapping was conducted by genotyping 1218 RILs using new simple sequence repeat (SSR) markers, which were developed by referring to the sequences of the wheat line Chinese Spring (IWGSC RefSeq v1.0). QYr.cau-1DL was mapped within a 0.5 cM (5.2 Mb) interval delimited by the SSR markers 1D-320.58 and 1D-325.79. These markers were applied to select for QYr.cau-1DL by screening F 2 or BC 4 F 2 plants of the wheat crosses RL6058 × QSM, Lantian10 × QSM and Yannong21 × QSM. F 2:3 or BC 4 F 2:3 families derived from the selected plants were assessed for stripe rust resistance in the fields of two locations and in a greenhouse. Wheat plants carrying the resistant marker haplotype in homozygous state for QYr.cau-1DL showed lower stripe rust severities (by 44% to 48%) than plants lacking this QTL. The trial of RL6058 (a carrier of Yr18 ) × QSM also indicated that QYr.cau-1DL had larger effect than Yr18 on reducing severity; they acted synergistically, yielding an elevated level of stripe rust resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Wang, Feng, Du, Zhang, Zhang, Che, Ren, Wang and Quan.)

The CRISPR/Cas system is known as one of the directions of the next generation of mainstream molecular diagnostic technology. However, most current CRISPR/Cas molecular diagnostics still rely on the pre-amplification of nucleic acid due to the limited sensitivity of CRISPR/Cas alone, which has no significant advantage over commercial Taqman-PCR and TwistAmp® Exo kits. Herein, we report an aM-level sensitive cascade CRISPR-Dx system (ASCas) that eliminates nucleic acid pre-amplification, thus avoiding aerosol contamination and greatly reducing the testing environment and personnel skill requirements for molecular diagnostics. Most importantly, the Cas13a nucleases with high sensitivity and trans-cleavage efficiency can rapidly cleaved RNA bubbles on the hybridized cascade probe at low concentration target RNA detection, which results in the destruction of the cascade probe and releases a large amount of trigger DNA for further signal amplification of secondary Cas12a reactions. Therefore, the ASCas system achieves amplification-free, ultra-sensitivity (1 aM), and ultra-fast (20 min) RNA detection. In addition, the ASCas system replaces the complicated screening process of primers and probes with the programmed Cas13a-crRNA design so that a suitable detection system can be constructed more quickly and straightforwardly for the mutation-prone SARS-CoV-2 virus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Conventional chemotherapy for multiple myeloma (MM) faces the challenges of a low complete remission rate and transformation to recurrence/refractory. The current MM first-line clinical drug Bortezomib (BTZ) faces the problem of enhanced tolerance and nonnegligible side effects. B cell maturation antigen (BCMA), for its important engagement in tumor signaling pathways and novel therapy technologies such as Chimeric antigen receptor T-Cell immunotherapy (CAR-T) and Antibody Drug Conjugate (ADC), has been identified as an ideal target and attracted attention in anti-MM therapy. Emerging nanotechnology provided feasible methods for drug delivery and new therapeutic strategies such as photothermal therapy (PTT). Herein, we developed a BCMA-Targeting biomimetic photothermal nanomissile BTZ@BPQDs@EM @anti-BCMA (BBE@anti-BCMA) by integration of BTZ, black phosphorus quantum dots (BPQDs), Erythrocyte membrane (EM) and BCMA antibody (anti-BCMA). We hypothesized that this engineered nanomissile could attack tumor cells in triple ways and achieve effective treatment of MM. Consequently, the intrinsic biomimetic nature of EM and the active targeting property of anti-BCMA enhanced the accumulation of therapeutic agents in the tumor site. Besides, owing to the decrease in BCMA abundance, the potential apoptosis-inducing ability was revealed. With the support of BPQDs' photothermal effect, Cleaved-Caspase-3 and Bax signal increased significantly, and the expression of Bcl-2 was inhibited. Furthermore, the synergistic photothermal/chemo therapy can effectively inhibit tumor growth and reverse the disorder of NF-κB in vivo. Importantly, this biomimetic nanodrug delivery system and antibody induced synergistic therapeutic strategy efficiently killed MM cells with ignorable systemic toxicity, which is a promising method for the future anticancer treatment of hematological malignancies in clinics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

To investigate the influence of the weak layer dip angle on the creep rupture of the composite rock mass, this paper conducts a graded loading creep experiment on the composite rock mass with different dip angles using the acoustic emission method to examine the fracture evolution process. With increasing load grade, the cumulative total ring count of the rock mass shows a "U"-shaped trend, and the acoustic emission spatial positioning results show that acoustic emission events in the rock mass fracture process are primarily concentrated in the vicinity of the weak layer, while events in other areas are few and dispersed. For rock masses with weak layer dip angles of 0° and 15°, cracks occur in both soft and hard rocks, where shear cracks are dominant in soft rocks, tensile cracks are dominant in hard rocks, and finally, the rock mass mainly exhibits tensile splitting failure. For rock masses with weak layer dip angles of 30° and 45°, most of the cracks exist in the interior of the soft rock, which is dominated by shear cracks. With increasing graded loads, the shear cracks continue to develop along the direction of the weak layer, the upper rock mass keeps slipping and dislocating, and the final failure mode is mainly shear-slip failure. The damage evolution varies with the inclination angle of the weak layer, which can be divided into three stages: initial damage accumulation, damage acceleration, and damage destruction. This demonstrates the ability to predict, prevent, and control the occurrence of creep disasters in rock masses with weak layers., (© 2023. The Author(s).)

Background: Ginsenoside compound K (CK), the main active metabolite in Panax ginseng , has shown good safety and bioavailability in clinical trials and exerts neuroprotective effects in cerebral ischemic stroke. However, its potential role in the prevention of cerebral ischemia/reperfusion (I/R) injury remains unclear. Our study aimed to investigate the molecular mechanism of ginsenoside CK against cerebral I/R injury., Methods: We used a combination of in vitro and in vivo models, including oxygen and glucose deprivation/reperfusion induced PC12 cell model and middle cerebral artery occlusion/reperfusion induced rat model, to mimic I/R injury. Intracellular oxygen consumption and extracellular acidification rate were analyzed by Seahorse multifunctional energy metabolism system; ATP production was detected by luciferase method. The number and size of mitochondria were analyzed by transmission electron microscopy and MitoTracker probe combined with confocal laser microscopy. The potential mechanisms of ginsenoside CK on mitochondrial dynamics and bioenergy were evaluated by RNA interference, pharmacological antagonism combined with co-immunoprecipitation analysis and phenotypic analysis., Results: Ginsenoside CK pretreatment could attenuate mitochondrial translocation of DRP1, mitophagy, mitochondrial apoptosis, and neuronal bioenergy imbalance against cerebral I/R injury in both in vitro and in vivo models. Our data also confirmed that ginsenoside CK administration could reduce the binding affinity of Mul1 and Mfn2 to inhibit the ubiquitination and degradation of Mfn2, thereby elevating the protein level of Mfn2 in cerebral I/R injury., Conclusion: These data provide evidence that ginsenoside CK may be a promising therapeutic agent against cerebral I/R injury via Mul1/Mfn2-mediated mitochondrial dynamics and bioenergy., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Isolation of circulating fetal nucleated red blood cells (cfNRBCs) from maternal peripheral blood provides a superior strategy for noninvasive prenatal genetic diagnosis. Recent technical advances in single-cell isolation and genetic analyses have promoted the clinical application of circulating fetal cell-based noninvasive prenatal diagnosis. However, the lack of highly specific ligands for rare circulating fetal cell enrichment from massive maternal cells significantly impedes the clinical transformation progress. In this work, aptamers specific to NRBCs were developed through clinical sample-based cell-SELEX. Herein, the complex clinical system provides natural selection stringency through binding competition between target and background cells, and it empowers aptamers with high specificity. An aptamer-based strategy was also established to isolate cfNRBCs from maternal peripheral blood. Results show the remarkable selectivity and affinity of developed aptamers, enabling efficient enrichment of cfNRBCs from abundant maternal cells. Moreover, screening for fetal sex and trisomy syndrome achieved high accuracy through chromosome analysis of enriched cfNRBCs. To the best of our knowledge, this is the first report to develop aptamer ligands for cfNRBC enrichment, providing an efficient strategy to screen cfNRBC-specific ligands and demonstrating broad application potential for cfNRBC-based noninvasive prenatal diagnosis.

Due to the excellent biocompatible physicochemical performance, luminogens with aggregation-induced emission (AIEgens) characteristics have played a significant role in biomedical fluorescence imaging recently. However, screening AIEgens for special applications takes a lot of time and efforts by using conventional chemical synthesis route. Fortunately, artificial intelligence techniques that could predict the properties of AIEgen molecules would be helpful and valuable for novel AIEgens design and synthesis. In this work, we applied machine learning (ML) techniques to screen AIEgens with expected excitation and emission wavelength for biomedical deep fluorescence imaging. First, a database of various AIEgens collected from the literature was established. Then, by extracting key features using molecular descriptors and training various state-of-the-art ML models, a multi-modal molecular descriptors strategy has been proposed to extract the structure-property relationships of AIEgens and predict molecular absorption and emission wavelength peaks. Compared to the first principles calculations, the proposed strategy provided greater accuracy at a lower computational cost. Finally, three newly predicted AIEgens with desired absorption and emission wavelength peaks were synthesized successfully and applied for cellular fluorescence imaging and deep penetration imaging. All the results were consistent successfully with our expectations, which demonstrated the above ML has a great potential for screening AIEgens with suitable wavelengths, which could boost the design and development of novel organic fluorescent materials., (© 2023. The Author(s).)

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. However, challenges in early diagnosis, high risk of liver metastasis, and lack of effective targeted therapy lead to poor prognosis and high mortality of UM. Therefore, generating an effective molecular tool for UM diagnosis and targeted treatment is of great significance. In this study, a UM-specific DNA aptamer, PZ-1, was successfully developed, which could specifically distinguish molecular differences between UM cells and noncancerous cells with nanomolar-range affinity and presented excellent recognition ability for UM in vivo and clinical UM tissues. Subsequently, the binding target of PZ-1 on UM cells was identified as JUP (junction plakoglobin) protein, which held great potential as a biomarker and therapeutic target for UM. Meanwhile, the strong stability and internalization capacity of PZ-1 were also determined, and a UM-specific aptamer-guided "nanoship" was engineered to load and selectively release doxorubicin (Dox) to targeted UM cells, with lower toxicity to nontumor cells. Taken together, the UM-specific aptamer PZ-1 could serve as a molecular tool to discover the potential biomarker for UM and to achieve the targeted therapy of UM.

A fluorescent probe was developed for the detection of phosgene based on 1,8-naphthalimide, of which o-diaminobenzene was used as the recognition moiety. The probe does not fluoresce due to nonradiative decay. The probe reacts rapidly with phosgene via an intramolecular cyclization reaction, which induces large fluorescence due to increased rigidity in the resulting molecule and a low detection limit (0.23 nM). This probe has excellent selectivity for phosgene against competing interference analytes and, in the form of probe-loaded test paper, is an extremely sensitive method for phosgene sensing in the gas phase below 1 ppm concentrations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Key Message: A novel QTL (QSt.nftec-2BL) was mapped to a 0.7 cM interval on chromosome 2B. Plants carrying QSt.nftec-2BL produced higher grain yields by up to 21.4% than otherwise in salinized fields. Wheat yield has been limited by soil salinity in many wheat-growing areas globally. The wheat landrace Hongmangmai (HMM) possesses salt tolerance as it produced higher grain yields than other tested wheat varieties including Early Premium (EP) under salt stresses. To detect QTL underlying this tolerance, wheat cross EP × HMM was chosen to serve as mapping population that was homozygous at Ppd (photoperiod response gene), Rht (reduced plant height gene) and Vrn (vernalization gene); thus, interference with QTL detection by these loci could be minimized. QTL mapping was conducted firstly using 102 recombinant inbred lines (RILs) that were selected from the EP × HMM population (827 RILs) for similarity in grain yield under non-saline condition. Under salt stresses, however, the 102 RILs varied significantly in grain yield. These RILs were genotyped using a 90 K SNP (single nucleotide polymorphism) array; consequently, a QTL (QSt.nftec-2BL) was detected on chromosome 2B. Then, using 827 RILs and new simple sequence repeat (SSR) markers developed according to the reference sequence IWGSC RefSeq v1.0, location of QSt.nftec-2BL was refined to a 0.7 cM (6.9 Mb) interval flanked by SSR markers 2B-557.23 and 2B-564.09. Selection for QSt.nftec-2BL was performed based on the flanking markers using two bi-parental wheat populations. Trials for validating effectiveness of the selection were conducted in salinized fields in two geographical areas and two crop seasons, demonstrating that wheat plants with the salt-tolerant allele in homozygous status at QSt.nftec-2BL produced higher grain yields by up to 21.4% than otherwise., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The herbal pairing of Huangqi and Dangshen (HD) is traditional Chinese herbal medicine and has been widely used in China, especially to treat myasthenia gravis (MG). However, the mechanism of HD on MG is unclear. Aim of the Study . This study aims to investigate HD's possible role in MG treatment. Materials and Methods . The TCMSP database was used to identify the active chemicals and their targets. The GeneCards, DisGeNET, and OMIM databases were used to search for MG-related targets. The STRING database was employed in order to identify the common PPI network targets. We next utilised Cytoscape 3.8.2 for target identification and the DAVID database for gene ontology (GO) function analysis as well as Encyclopaedia of Genomes (KEGG) pathway enrichment analysis on the selected targets. The AutoDock Vina software was used to test the affinity of essential components with the hub gene before concluding that the primary targets were corrected through molecular docking. Results . 41 active compounds were screened from HD, and the number of putative-identified target genes screened from HD was 112. There were 21 target genes that overlapped with the targets of MG, which were postulated to be potential treatment targets. Through further analysis, the results showed that the active compounds from HD (such as 7-methoxy-2-methylisoflavone, quercetin, luteolin, Kaempferol, and isorhamnetin) may achieve the purpose of treating MG by acting on some core targets and related pathways (such as EGFR, FOS, ESR2, MYC, ESR1, CASP3, and IL-6). Molecular docking findings demonstrated that these active molecules have a near-perfect ability to attach to the primary targets. Conclusion . Through network pharmacology, the findings in this study provide light on the coordinated action of several HD formula components, targets, and pathways. It provided a theoretical basis for further study of HD pharmacological action., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Miao Liu et al.)

Different from the conventional piezochromic materials with a mono-redshift of single emission, our well-designed molecule demonstrates a sensitive turn-on and color-tunable piezochromic luminescence in response to the hydrostatic pressure. The molecule PXZ-W-SOF possesses dual-emission and pressure-induced bidirectional shifting characteristics. On the basis of in-depth experimental studies, on one hand, it is confirmed that the origin of the dual-emission behavior is the intramolecular charge transfer, namely thermally activated delayed fluorescence (TADF), and the intermolecular excimer; on the other hand, the emission of the excimer exhibits three-step variations with increasing pressure, which is mainly attributed to the molecular structure and its crystal packing state. The remarkable color change of PXZ-W-SOF from sky-blue to green to deep-blue during the whole process of boosting and releasing pressure is a result of intramolecular and intermolecular energy-transfer interactions. The PXZ-W-SOF molecular model is an extremely rare example of highly sensitive fluorescence tuning driven by TADF and excimer conversion under mechanical stimulation, thus providing a novel mechanism for the field of piezochromism. The unique molecular design also offers a new idea for rare deep-blue and ultraviolet TADF materials., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Immunosuppressive drugs are routinely used to treat myasthenia gravis (MG). However, current recommendations provide limited evidence to support treatment options, leading to considerable variation in practice among healthcare specialists. Hence, we present a protocol for a systematic review and network meta-analysis (NMA) to update the evidence by comparing the efficacy and acceptability of oral immunosuppressive drugs for the treatment of MG., Methods: We will conduct a systematic review and NMA of all randomized controlled trials evaluating the following oral immunosuppressive drugs for the treatment of MG. Published studies will be searched using the following databases from inception to November 23, 2021: CENTRAL, the CINAHL, MEDLINE, Embase, PsycINFO, Web of Science, and 3 Chinese databases (Chinese Biomedical Literatures Database, CNKI, and Wan Fang database). Assessment of study eligibility and data extraction will be conducted independently by 2 reviewers. The main outcome will be a quantitative MG scoring system. We will conduct Bayesian NMA to synthesize all evidence for each outcome and obtain a comprehensive ranking of all treatments. The quality of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations framework., Results: The objective of this study was to assess the relative clinical efficacy and acceptability of first-line immunosuppressants for the treatment of MG, using a systematic review and NMA approach., Conclusion: In the absence of head-to-head trials comparing therapies, evidence from this NMA of available clinical trials will inform clinicians, patients, and families the risk-benefit profiles of different treatment options., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Gene therapy has shown great potential in the treatment of many diseases by downregulating the expression of certain genes. The development of gene vectors as a vehicle for gene therapy has greatly facilitated the widespread clinical application of nucleic acid materials (DNA, mRNA, siRNA, and miRNA). Currently, both viral and non-viral vectors are used as delivery systems of nucleic acid materials for gene therapy. However, viral vector-based gene therapy has several limitations, including immunogenicity and carcinogenesis caused by the exogenous viral vectors. To address these issues, non-viral nanocarrier-based gene therapy has been explored for superior performance with enhanced gene stability, high treatment efficiency, improved tumor-targeting, and better biocompatibility. In this review, we discuss various non-viral vector-mediated gene therapy approaches using multifunctional biodegradable or non-biodegradable nanocarriers, including polymer-based nanoparticles, lipid-based nanoparticles, carbon nanotubes, gold nanoparticles (AuNPs), quantum dots (QDs), silica nanoparticles, metal-based nanoparticles and two-dimensional nanocarriers. Various strategies to construct non-viral nanocarriers based on their delivery efficiency of targeted genes will be introduced. Subsequently, we discuss the cellular uptake pathways of non-viral nanocarriers. In addition, multifunctional gene therapy based on non-viral nanocarriers is summarized, in which the gene therapy can be combined with other treatments, such as photothermal therapy (PTT), photodynamic therapy (PDT), immunotherapy and chemotherapy. We also provide a comprehensive discussion of the biological toxicity and safety of non-viral vector-based gene therapy. Finally, the present limitations and challenges of non-viral nanocarriers for gene therapy in future clinical research are discussed, to promote wider clinical applications of non-viral vector-based gene therapy.

The low sensitivity and poor selectivity of fluorescence sensors for real gaseous sarin detection greatly hinder their real-world applications. In this work, we report the development of a novel fluorophore with an active N-H vibration in the benzimidazole group for the sensitive detection of gaseous sarin. We demonstrate that the interactions between the nucleophilic fluorine atom in sarin and the electrophilic hydrogen atom in the benzimidazole group of the fluorophore can restrict the N-H vibration to yield sensitive fluorescence-enhancing responses. On the basis of this mechanism, the experimental and theoretical limits of detection for gaseous sarin can reach as low as 50 and 4.8 ppb, respectively. We further coassemble this fluorophore with another two D-A fluorophores containing different acceptor groups and use the resulting coassemblies as sensor array members to obtain access to differential combined responses to gaseous sarin compared with various interferents, including diethylchlorophosphate and acids. This two-member sensor array proves to be capable of detecting trace sarin in complex environments, demonstrating its potential applications in the real world.

In the pursuit of designing van der Waals magnetic tunneling junctions (vdW-MTJs) with two-dimensional (2D) intrinsic magnets, as well as to quantitatively reveal the microscopic nature governing the vertical tunneling pathways beyond the phenomenological descriptions on CrI 3 -based vdW-MTJs, we investigate the structural configuration, electronic structure and spin-polarized quantum transport of graphene|2 monolayer(2ML)-CrI 3 |graphene heterostructure with Ag(111) layers as the electrode, using density functional theory (DFT) and its combination of non-equilibrium Green's function (DFT-NEGF) methods. The in-plane lattice of CrI 3 layers is found to be stretched when placed on the graphene (Gr) layer, and the layer-stacking does not show any site selectivity. The charge transfer between CrI 3 and Gr layers make the CrI 3 layer lightly electron-doped, and the Gr layer hole-doped. Excitingly, the inter-layer hybridization between graphene and CrI 3 layers render the CrI 3 layer metallic in the majority spin channel, giving rise to an insulator-to-half-metal transition. Due to the metallic/insulator characteristics of the spin-majority/minority channel of the 2ML-CrI 3 barrier in vdW-MTJs, Gr|2ML-CrI 3 |Gr heterostructures exhibit an almost perfect spin filtering effect (SFE) near the zero bias in parallel magnetization, a giant tunneling magnetoresistance (TMR) ratio up to 2 × 10 4 %, and remarkable negative differential resistance (NDR). Our results not only give an explanation for the observed giant TMR in CrI 3 -based MTJs but also show the direct implications of 2D magnets in vdW-heterostructures., Competing Interests: All authors declare that they have no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Myasthenia gravis (MG) is a rare and refractory autoimmune disease, and Qi Shen Di Huang (QSDH) drug formulary is an in-hospital herbal decoction with proven clinical efficacy in treating MG. Currently, most of the research on the QSDH drug formulary has concentrated on its clinical efficacy, and there is a lack of systematic study on the material basis. The active compounds and their mechanism of action have not been entirely determined. Therefore, this study sought to identify the active compounds in the QSDH drug formulary and analyze the key targets and potential mechanisms. We used ultra-performance liquid chromatography Q Exactive-mass spectrometry (UHPLC-QE-MS) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database to identify and screen 85 active ingredients corresponding to 59 potential targets (17 herbs) associated with myasthenia gravis, and further identified AKT1 as the primary core target and the PI3K/AKT signaling pathway as the most substantial enriched pathway. Molecular docking and UPLC-MS analysis identified quercetin, luteolin, wogonin, kaempferol, laccasein, and epigallocatechin gallate are the core compounds of the QSDH drug formulary. In vivo rat studies showed that the QSDH drug formulary reduced Lennon's clinical score and decreased acetylcholine receptor antibody levels in peripheral blood rats with experimental autoimmune myasthenia gravis. In addition, the QSDH drug formulary downregulated P-PI3K/PI3K and P-Akt/Akt protein expression. Collectively, these findings describe the role and potential mechanism of the QSDH drug formulary in the treatment of MG, which exerts potential value by acting on AKT targets and regulating the PI3K/AKT signaling pathway and providing a theoretical reference for QSDH drug formulary application in the clinical treatment of MG., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Yibin Zhang et al.)

PROteolysis TArgeting Chimeras (PROTACs) induce targeted protein degradation by hijacking the intracellular ubiquitin proteasome system, thus emerging as a new strategy for drug development. However, most PROTACs generated lack cell-type selectivity and are poorly soluble in water. To address this drawback, we developed a novel PROTAC ZL216 using aptamer AS1411 as a targeting ligand of nucleolin to conjugate with a small molecule ligand of E3 ligase VHL, which shows high aqueous solubility and serum stability. Based on the differential expression of nucleolin on the cell surface, ZL216 could bind to and internalize into breast cancer cells, but not normal breast cells. Furthermore, we revealed that ZL216 promoted the formation of a nucleolin-ZL216-VHL ternary complex in breast cancer cells and potently induced nucleolin degradation in vitro and in vivo . As a result, ZL216 inhibited the proliferation and migration of breast cancer cells. These studies demonstrate that in addition to peptides and small molecule compounds, nuclei acid aptamers can also be used to generate PROTACs, which broadens the toolbox constructing PROTACs and provides a promising strategy for development of tumor-selective PROTACs., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Purpose: We aimed to assess factors influencing the occurrence of delayed hyponatremia after transsphenoidal surgery in patients with Rathke's cleft cysts (RCCs)., Methods: We retrospectively collected the clinical data of patients who underwent transsphenoidal surgery for RCCs from January 2014 to January 2022. Univariate and multivariate analyses were used to determine the factors influencing the occurrence of postoperative delayed hyponatremia., Results: Of the 78 microscopic transsphenoidal surgery recipients with RCCs, 15 experienced postoperative delayed hyponatremia. There were 35 men and 43 women, and mean age was 43.75 ± 14.95 years. The clinical manifestations of RCCs were headache (62 cases, 79.5%), visual dysfunction (35 cases, 44.9%), endocrine dysfunction symptoms (12 cases, 15.4%). After transsphenoidal surgery, 93.5% (58/62) had improvements in headache, and 97.1% (34/35) had improved or resolved compressive visual symptoms. Delayed hyponatremia occurred on average on day 6.46 and lasted on average for 4.40 days. Logistic regression analysis showed that the independent influencing factor of delayed hyponatremia after transsphenoidal surgery in patients with RCCs was postoperative diaphragma sellae height., Conclusion: Postoperative diaphragma sellae height was identified as an independent influencing factor for delayed hyponatremia after transsphenoidal surgery in patients with RCCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Pei, Zhang, Feng and Wang.)

Long non-coding RNAs (lncRNAs) have been reported to be vital participants in tumor progression. Recently, lncRNA PSMB8-AS1 has been uncovered to facilitate pancreatic cancer progression by regulating miR-382-3p/STAT1/PD-L1 network. Nonetheless, the role of PSMB8-AS1 and its underlying mechanism have not been well-explored in colorectal cancer (CRC). The expression of RNAs or proteins was detected via qRT-PCR or western blot assays. Functional assays were involved in evaluating the effects of PSMB8-AS1/miR-1299/ADAMTS5 on the malignant behaviors of CRC cells. The molecular mechanism of PSMB8-AS1 was explored via mechanism analyses in CRC cells. Based on experimental results, PSMB8-AS1 expression was notably higher in CRC cell lines than in normal cells. The downregulation of PSMB8-AS1 repressed cell viability, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of CRC while promoting cell apoptosis. It was also revealed that PSMB8-AS1 could sponge miR-1299 to upregulate ADAMTS5 in CRC cells. In rescue assays, we further discovered that miR-1299 inhibition or ADAMTS5 overexpression abrogated the suppressive influence of PSMB8-AS1 deficiency on CRC cell growth. In addition, PSMB8-AS1 was validated to induce M2 polarization. In conclusion, PSMB8-AS1 sponges miR-1299 to increase PSMB8-AS1 expression, thus promoting CRC cell growth.

The oncogenic role of circular RNA ENTPD7 (circENTPD7) in cancer biology has been reported in glioblastoma, while its role in non-small cell lung cancer (NSCLC) is unknown. This study was performed to investigate the involvement of circENTPD7 in NSCLC. NSCLC tissues and paired non-tumor tissues were collected from 64 NSCLC patients and the expression of circENTPD7 and PTEN were determined by RT-qPCR. Expression levels of PTEN protein in these tissue samples were measured by ELISA. The 64 NSCLC patients were subjected to a follow-up study to explore the role of circENTPD7 in predicting the survival of NSCLC. Overexpression of circENTPD7 was achieved in NSCLC cells, and the effects of overexpression of circENTPD7 on the expression of PTEN were measured by RT-qPCR and Western blot at mRNA and protein level, respectively. Cell proliferation was assessed by CCK-8 assay. CircENTPD7 was upregulated in NSCLC and high expression levels of circENTPD7 predicts the poor survival rate of NSCLC cells. In NSCLC tissues, circENTPD7 was inversely correlated with PTEN protein but not mRNA. In NSCLC tissues, overexpression of circENTPD7 resulted in downregulation of PTEN, but did not alter the expression of PTEN mRNA. Cell proliferation analysis showed that overexpression of circENTPD7 promoted the proliferation of NSCLC cells and reduced the inhibitory effects of overexpression of PTEN on cell proliferation. CircENTPD7 may suppress the accumulation of PTEN to promote cell proliferation in NSCLC.

A near-infrared fluorescent probe was prepared for selective detection of reduced nicotinamide adenine dinucleotide (NADH) in live cells. The probe turns off the fluorescence with a closed spironolactone switch. However, reduction of the probe by NADH turns on fluorescence at 740 nm. Theoretical calculations suggest a more planar arrangement between the rhodamine and quinoline moieties with increased π-delocalization resulting from reduction., (Copyright © 2022 Elsevier Inc. All rights reserved.)