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Background: Intraoperative molecular imaging (IMI) uses a fluorescent probe to identify occult cancers. VGT-309 is a quenched activity-based probe that is activated in the presence of cathepsins, enzymes overexpressed in cancer cells, and detected by near-infrared (NIR) light. This study aims to evaluate the sensitivity and the positive predictive value (PPV) of robotic-assisted thoracic surgery (RATS) with intraoperative molecular imaging (RIMI) using VGT-309 to localize tumors using NIR light to detect areas with increased cathepsin activity. Our secondary outcome was to compare RIMI to video-assisted thoracic surgery (VATS) with intraoperative molecular imaging (VIMI)., Methods: In a phase 2 clinical trial at the University of Pennsylvania, patients (n=10) with suspicious pulmonary lesions underwent RATS. First, white light was used followed by RIMI to identify tissues with increased cathepsin activity. Then, VIMI was performed to compare the sensitivity and PPV in identifying the cathepsin activity. The resected specimens were then evaluated for fluorescence and underwent histopathological analysis for cathepsin expression. Image analysis was performed using ImageJ software. Statistical analysis was conducted using IBM SPSS Statistics software. A P value of 0.05 or less was considered significant., Results: RATS with white light identified 6 out of the 10 pulmonary nodules, whereas adding RIMI identified an additional 4 more pulmonary nodules. RIMI and VIMI were able to detect the same 8/10 (80%) nodules. The addition of VIMI did not identify any lesions that RIMI may have missed. The mean fluorescence intensity of tumors visualized by RIMI was 115.81 A.U. [standard deviation (SD) =58.57] compared to 95.6 A.U. (SD =14.81) by VIMI (P=0.41). The mean tumor-to-background ratios (TBR) of tumors visualized by RIMI was 9.20 (SD =9.12) compared to 2.29 A.U. (SD =1.11) using VIMI (P=0.1). The sensitivity of RIMI and VIMI was 88.9% which was superior to that of RATS (55.6%). The PPV of RATS was 83.3% compared to 100% in RIMI and VIMI., Conclusions: RIMI is a valuable option for visualization of occult disease using VGT-309-guided IMI through identifying areas of increased cathepsin activity. In this small series, RIMI and VIMI showed clinical equivalence in sensitivity and PPV of detecting cathepsin activity., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-370/coif). J.T.S. Jr and E.S.B. report that they receive salary and stock options as full-time employees of the company. The company also provided study drug (VGT-309) and funding for the clinical trial at the University of Pennsylvania where the data in the manuscript were generated. Vergent Bioscience is the awardee of SBIR grant R44CA277890, which supports the clinical trial at the University of Pennsylvania where the data in the manuscript were generated. As employees of the company, Vergent pays expenses for J.T.S. Jr and E.S.B. to travel to and attend scientific meetings. They are inventor on a pending patent application owned by Vergent. As employees of the company, they have stock options in the company. They are executives of the company and receives a salary as a full-time employee. The other authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

Phytoestrogens (PEs) may harm liver function. However, studies in pregnant women are limited. Our study was conducted in pregnant women to assess the effect of serum PEs on liver function markers. We conducted a cross-sectional study focusing in the first trimester of pregnancy. A total of 352 pregnant women were enrolled in the study. We used generalized linear model (GLM) to explore the associations between each PE and each marker of liver function. We used Quantile g-computation (Qgcomp) and Bayesian kernel machine regression (BKMR) models to explore the associations between mixed exposure to all PEs and liver function markers. The GLM results showed that equol (EQU), daidzein (DAD), genistein (GEN), enterolactone (ENT), and enterodiol (END) were negatively correlated with albumin (ALB). DAD and GEN were associated with elevated alanine aminotransferase (ALT). DAD, GEN, naringin (NAR), and glycitein (GLY) were related to elevated aspartate aminotransferase (AST). Mixed exposure model results showed that the mixture of PEs was associated with reduced ALB. Our results support the existence of associations between PEs and maternal liver function in the first trimester. Emphasizing the detrimental associations between serum PEs and liver function in pregnant women is essential to ensure maternal liver health during pregnancy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cervical squamous cell carcinoma (CSCC) exhibits a limited response to immune-checkpoint blockade. Here we conducted a multiomic analysis encompassing single-cell RNA sequencing, spatial transcriptomics and spatial proteomics, combined with genetic and pharmacological perturbations to systematically develop a high-resolution and spatially resolved map of intratumoral expression heterogeneity in CSCC. Three tumor states (epithelial-cytokeratin, epithelial-immune (Epi-Imm) and epithelial senescence), recapitulating different stages of squamous differentiation, showed distinct tumor immune microenvironments. Bidirectional interactions between epithelial-cytokeratin malignant cells and immunosuppressive cancer-associated fibroblasts form an immune exclusionary microenvironment through transforming growth factor β pathway signaling mediated by FABP5. In Epi-Imm tumors, malignant cells interact with natural killer and T cells through interferon signaling. Preliminary analysis of samples from a cervical cancer clinical trial ( NCT04516616 ) demonstrated neoadjuvant chemotherapy induces a state transition to Epi-Imm, which correlates with pathological complete remission following treatment with immune-checkpoint blockade. These findings deepen the understanding of cellular state diversity in CSCC., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Non-line-of-sight (NLOS) imaging techniques have the ability to reconstruct objects beyond line-of-sight view, which would be useful in a variety of applications. In transient NLOS techniques, a fundamental problem is that the time resolution of imaging depends on the single-photon timing resolution (SPTR) of a detector. In this paper, a temporal super-resolution method named temporal encoding non-line-of-sight (TE-NLOS) is proposed. Specifically, by exploiting the spatial-temporal correlation among transient images, high-resolution transient images can be reconstructed through modulator encoding. We have demonstrated that the proposed method is capable of reconstructing transient images with a time resolution of 20 picoseconds from a detector with a limited SPTR of approximately nanoseconds. In systems with low time jitter, this method exhibits superior accuracy in reconstructing objects compared to direct detection, and it also demonstrates robustness against miscoding. Utilizing high-frequency modulation, our framework can reconstruct accurate objects with coarse-SPTR detectors, which provides an enlightening reference for solving the problem of hardware defects.

To solve the durability of flexible base asphalt pavement, especially its anti-rutting problem, a design method on durable asphalt pavement of flexible base on anti-rutting performance was put forward in the paper, based on many experiments and calculations. Firstly, a method that asphalt could be selected according to penetration and the anti-rutting factor of its base asphalt was found, which solved the problem of the asphalt selection of the flexible base asphalt mixture design. Meanwhile, a method of skeleton-density structure gradation design was proposed based on the fractal void ratio of coarse aggregate, fractal volume of fine aggregate in coarse aggregate, penetration, fractal dimension of gradation particle size, and rutting tests, which effectively solved in advance the rutting and fatigue performance of flexible base asphalt mixtures. Then, on the basis of the fatigue damage, a calculation method of fatigue life was suggested, which solved the problem that the fatigue damage of asphalt mixtures rarely considered the combined effects of creep damage and fatigue damage. In addition, a calculation method of rutting was formulated based on vehicle dynamic load and ANSYS 16.0 software. Lastly, the feasibility of the design method on durable asphalt pavement of flexible base on anti-rutting performance was verified combining with the real engineering of a supporting project and several numerical calculations and tests.

Increased vegetation peak growth and phenological shifts toward spring have been observed in response to climate warming in the temperate regions. Such changes have the potential to modify warming by perturbing land‒atmosphere energy exchanges; however, the signs and magnitudes of biophysical feedback on surface temperature in different biomes are largely unknown. Here, we synthesized information from vegetation growth proxies, land surface temperature (LST), and surface energy balance factors (surface evapotranspiration (ET), albedo, and broadband emissivity (BBE)) to investigate the variations in timing (PPT) and productivity (PP max ) of seasonal peak photosynthesis and their time-lagged biophysical feedbacks to the post-season LST in Inner Mongolia (IM) during 2001-2020. We found that increased PP max , rather than advanced PPT, exhibited a significant impact on LST, with divergent signs and magnitudes across diurnal periods and among different biomes. In the grassland biome, increased PP max cooled both LST during daytime (LST day ) and nighttime (LST night ) throughout the post-season period, with a more pronounced response during daytime and diminishing gradually from July to September. This cooling effect on LST was primarily attributed to enhanced ET, as evidenced by the greater effect of ET cooling than that of albedo warming and BBE cooling based on a structural equation model (SEM). In the forest biome, increased PP max led to a symmetrical warming effect on LST day and LST night , and none of the surface energy balance factors were identified as significant intermediate explanatory factors for the observed warming effect. Moreover, the responses of average LST (LST mean ) and diurnal temperature range of LST (LST DTR ) to variations in PP max were consistent with those of LST day at two biomes. The observations above elucidate the divergent feedback mechanisms of vegetation peak growth on LST among different biomes and diurnal cycles, which could facilitate the improvement of the realistic parameterization of surface processes in global climate models., 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.)

Thermoelectric technology can be utilized to directly convert waste heat into electricity, aiming at energy harvesting in an environmentally friendly manner. As a promising p-type thermoelectric material, CuInTe 2 possesses a high inherent lattice thermal conductivity, which limits the practical implementation in the field of thermoelectricity. Herein, through the combination of vacuum melting and annealing along with hot-pressure sintering techniques, we demonstrated that CuIn 0.95 Ag 0.05 Te 2 thermoelectric materials with trace Ag doping can exhibit a notably high Seebeck coefficient of 614 μV/K, arising from the high density-of-states effective mass and reduced carrier concentration. Owing to the diminished lattice thermal conductivity derived from Umklapp scattering induced by point defects and dislocation, stemming from the trace Ag doping at In sites rather than Cu sites, CuIn 0.95 Ag 0.05 Te 2 exhibited a maximum figure of merit ( ZT ) of 1.38 at 823 K, an 18% enhancement over pristine CuInTe 2 , leading to a maximum average ZT of 0.67 across temperatures ranging from 303 to 823 K. In essence, our work underscores the efficacy of doping engineering and point defects in tailoring the thermoelectric performance of CuInTe 2 -based materials. This study not only contributes to advancing the fundamental understanding of thermoelectric enhancement but also lays out a practical pathway toward the realization of high-performance CuInTe 2 -based thermoelectric materials.

Effectively imaging through dynamic scattering media is of great importance and challenge. Some imaging methods based on physical or learning models have been designed for object reconstruction. However, with an increase in exposure time or more drastic changes in the scattering medium, the speckle pattern superimposed during camera integration time undergoes more significant changes, resulting in a modification of the collected speckle structure and increased blurring, which brings significant challenges to the reconstruction. Here, the clearer structural information of blurred speckles is unearthed with a presented speckle de-blurring algorithm, and a high-throughput imaging method through rapidly changing scattering media is proposed for reconstruction under long exposure. For the problem of varying blur degrees in different regions of the speckle, a block-based method is proposed to divide the speckle into distinct sub-speckles, which can realize the reconstruction of hidden objects. The imaging of hidden objects with different complexity through dynamic scattering media is demonstrated, and the reconstruction results are improved significantly for speckles with different blur degrees, which verifies the effectiveness of the method. This method is a high-throughput approach that enables non-invasive imaging solely through the collection of a single speckle. It directly operates on blurred speckles, making it suitable for traditional speckle-correlation methods and deep learning (DL) methods. This provides a new way of thinking about solving practical scattering imaging challenges.

Polydimethyl glutarimide (PMGI) layers with sub-micron thicknesses have been modified in a 2.5 kV Ar plasma immersion ion implantation (PIII) process to introduce free radical covalent binding sites. The surface roughness of the PMGI increased after the PIII treatment but no through-layer defects were observed. When applied to the treated PMGI, horseradish peroxidase (HRP) enzyme remained bound to the surface after extended immersion in sodium dodecyl sulfate solution (SDS). Hence, covalent binding between the activated surface and enzyme was confirmed. This covalent binding was achieved up to 24-h after the PIII process. The treated PMGI was then incorporated as a gate dielectric layer within a lateral three-terminal electrolyte-gated device. The device output characteristics resembled those of post-synaptic outputs; as successive (pre-synaptic) voltage pulses were applied to the gate, paired pulse depression and spike rate dependent plasticity were observed in the source-drain (post-synaptic) current. These characteristics were altered by the presence of HRP immobilised on the plasma-modified PMGI gate dielectric layer thus providing readout detection. These results and preliminary device characteristics show the potential for the plasma functionalized PMGI as a sensitive and reproducible biosensing technology., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jim Partridge, Dougal McCulloch, David McKenzie reports financial support was provided by Australian Research Council. David McKenzie, Enyi Guo reports financial support was provided by Motor Neurone Disease Australia., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The objective was to assess the performance of a context-enriched large language model (LLM) compared with international neurosurgical experts on questions related to the management of vestibular schwannoma. Furthermore, another objective was to develop a chat-based platform incorporating in-text citations, references, and memory to enable accurate, relevant, and reliable information in real time., Methods: The analysis involved 1) creating a data set through web scraping, 2) developing a chat-based platform called neuroGPT-X, 3) enlisting 8 expert neurosurgeons across international centers to independently create questions (n = 1) and to answer (n = 4) and evaluate responses (n = 3) while blinded, and 4) analyzing the evaluation results on the management of vestibular schwannoma. In the blinded phase, all answers were assessed for accuracy, coherence, relevance, thoroughness, speed, and overall rating. All experts were unblinded and provided their thoughts on the utility and limitations of the tool. In the unblinded phase, all neurosurgeons provided answers to a Likert scale survey and long-answer questions regarding the clinical utility, likelihood of use, and limitations of the tool. The tool was then evaluated on the basis of a set of 103 consensus statements on vestibular schwannoma care from the 8th Quadrennial International Conference on Vestibular Schwannoma., Results: Responses from the naive and context-enriched Generative Pretrained Transformer (GPT) models were consistently rated not significantly different in terms of accuracy, coherence, relevance, thoroughness, and overall performance, and they were often rated significantly higher than expert responses. Both the naive and content-enriched GPT models provided faster responses to the standardized question set than expert neurosurgeon respondents (p < 0.01). The context-enriched GPT model agreed with 98 of the 103 (95%) consensus statements. Of interest, all expert surgeons expressed concerns about the reliability of GPT in accurately addressing the nuances and controversies surrounding the management of vestibular schwannoma. Furthermore, the authors developed neuroGPT-X, a chat-based platform designed to provide point-of-care clinical support and mitigate the limitations of human memory. neuroGPT-X incorporates features such as in-text citations and references to enable accurate, relevant, and reliable information in real time., Conclusions: The present study, with its subspecialist-level performance in generating written responses to complex neurosurgical problems for which evidence-based consensus for management is lacking, suggests that context-enriched LLMs show promise as a point-of-care medical resource. The authors anticipate that this work will be a springboard for expansion into more medical specialties, incorporating evidence-based clinical information and developing expert-level dialogue surrounding LLMs in healthcare.

Background: Physical activity has been utilized as an effective strategy to prevent gestational diabetes mellitus (GDM). However, most pregnant women with high risk for GDM did not achieve the recommended physical activity level. Furthermore, relevant physical activity protocols have varied without theory-guided and evidence-based tailored to pregnant women with high risk for GDM. This study aimed to develop and pilot test a theory-guided and evidence-based physical activity intervention protocol for pregnant women with high risk for GDM., Methods: The study design was guided by the Medical Research Council Framework for Developing and Evaluating Complex Intervention (the MRC framework). The preliminary protocol for physical activity intervention was developed based on self-efficacy theory, research evidence identified from systematic reviews and clinic trials, stakeholder engagement, context, and economic considerations. The preliminary intervention protocol was validated through a content validity study by an expert panel of 10 experts. A single-blinded randomized controlled trial (RCT) was designed to test the feasibility and acceptability of the intervention., Results: The validity of the preliminary intervention protocol was excellent as consensus was achieved. The final 13 sessions of self-efficacy enhancing physical activity intervention protocol were developed, including knowledge education, exercise clinic visits and video, and group discussions with face-to-face and online blended sessions. In the feasibility study, 34 pregnant women with high risk for GDM were randomized for the intervention (n = 17) or the control group (n = 17). The recruitment and retention rates were 82.9% and 58.9%, respectively. Women in the intervention group had a lower incidence of GDM (26.7% vs. 36.5%) than the control group (P >0.05). All participants were satisfied with the intervention and agreed that the intervention was helpful., Conclusions: The developed self-efficacy-enhancing physical activity intervention is a feasible and acceptable intervention for enhancing physical activity among pregnant women with high risk for GDM and is ready to be tested in a more extensive RCT study., Trial Registration: The study was registered on 4 February 2022 (ChiCTR2200056355) by the Chinese Clini Trial Registry (CHiCTR)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To investigate the notion that a surgeon's force profile can be the signature of their identity and performance., Summary Background Data: Surgeon performance in the operating room is an understudied topic. The advent of deep learning methods paired with a sensorized surgical device presents an opportunity to incorporate quantitative insight into surgical performance and processes. Using a device called the SmartForceps System and through automated analytics, we have previously reported surgeon force profile, surgical skill, and task classification. However, an investigation of whether an individual surgeon can be identified by surgical technique has yet to be studied., Methods: In this study, we investigate multiple neural network architectures to identify the surgeon associated with their time-series tool-tissue forces using bipolar forceps data. The surgeon associated with each 10-second window of force data was labeled, and the data were randomly split into 80% for model training and validation (10% validation) and 20% for testing. Data imbalance was mitigated through subsampling from more populated classes with a random size adjustment based on 0.1% of sample counts in the respective class. An exploratory analysis of force segments was performed to investigate underlying patterns differentiating individual surgical techniques., Results: In a dataset of 2819 ten-second time segments from 89 neurosurgical cases, the best-performing model achieved a micro-average area under the curve of 0.97, a testing F1-score of 0.82, a sensitivity of 82%, and a precision of 82%. This model was a time-series ResNet model to extract features from the time-series data followed by a linearized output into the XGBoost algorithm. Furthermore, we found that convolutional neural networks outperformed long short-term memory networks in performance and speed. Using a weighted average approach, an ensemble model was able to identify an expert surgeon with 83.8% accuracy using a validation dataset., Conclusions: Our results demonstrate that each surgeon has a unique force profile amenable to identification using deep learning methods. We anticipate our models will enable a quantitative framework to provide bespoke feedback to surgeons and to track their skill progression longitudinally. Furthermore, the ability to recognize individual surgeons introduces the mechanism of correlating outcome to surgeon performance., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Pleurectomy and decortication (PD) in malignant pleural mesothelioma has a high morbidity mostly associated with aspiration pneumonia (PNA), deep vein thrombosis (DVT), and foreign catheter sepsis. We instituted four strategies to reduce these complications and report our experience., Methods: This was a retrospective review of patients who underwent PD at the University of Pennsylvania between 2015 and 2022. Our patients underwent standard of care PD in addition to tracheostomy and gastrostomy/jejunostomy tube with therapeutic anticoagulation (AC) leading up to surgery. Measured outcomes were postoperative PNA, DVT, and sepsis. The predicted risk of those same outcomes had patients not undergone the interventions was calculated based on the American College of Surgeons (ACS) surgical risk calculator (SRC). A McNemar's test was used to determine whether the risk of having PNA, DVT and sepsis differed between the two subgroups., Results: Fifty-five patients were included in the study. The mean age was 70 years (SD 6.2) with a mean of 21 (SD 19) pack-years of smoking. PNA, DVT, and catheter-related sepsis occurred in 12, four, and seven patients, respectively. Upon using the ACS SRC prediction model of the nonintervention group, PNA, DVT and catheter related sepsis was predicted to occur in 24 (paired data OR 5, 95% CI: 1.4-17.2; McNemar's test p = 0.008), 14 (paired data OR 3.5, 95% CI: 1.15-10.6; McNemar's test p = 0.03), and 17 (paired OR 3, 95% CI: 1.09-8.3; McNemar's test p = 0.04) patients, respectively., Discussion: Patients undergoing tracheostomy creation, therapeutic AC at the time of diagnosis, and gastrostomy tube placement had a reduced risk of aspiration PNA, DVT, and catheter sepsis., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: To explore the biological function and the underlying mechanisms of GOT2 in hepatocellular carcinoma (HCC). Materials & methods: The expression level and prognostic value of GOT2 were examined using International Cancer Genome Consortium and International Cancer Proteogenome Consortium databases. The cell counting kit-8 method, clone formation, Transwell ® assays and western blotting were used to evaluate the effects of GOT2 on the biological function and autophagy of HCC cells. Results: The expression of GOT2 was downregulated in HCC tissues and correlated with poor prognosis of HCC patients. Knockdown of GOT2 promoted proliferation, migration and invasion of HCC cells and promoted cells' proliferation by inducing autophagy. Conclusion: GOT2 plays a tumor-inhibitory role in HCC and may be a potential therapeutic target for HCC.

The drug resistance of single-target therapy has gradually become an intractable clinical problem. Combination therapy may be an effective treatment to overcome or postpone drug resistance in cancer. Herein, we discussed the synergistic effect of transforming acidic coiled-coil containing protein 3 (TACC3) suppression and cyclin-dependent kinase 1 (CDK1) in hepatocellular carcinoma (HCC). The Cancer Genome Atlas database and bioinformatics methods were implemented to analyze the expression of CDK1 and TACC3, and predict the biological function of TACC3-related genes in HCC. In addition, in vitro experiments, including cell counting kit 8, transwell and flow cytometry were utilized to evaluate cell proliferation, migration, invasion, cell cycle arrest and apoptosis of HCC cells. Our results demonstrated that TACC3 is an unfavorable and independent prognostic factor to predict poor overall survival (OS) in HCC patients. Genetic inhibition of TACC3 exhibited a remarkable antineoplastic activity of HCC cell lines. Bioinformatic prediction proposed that CDK1 may be the main regulator of TACC3-related genes in HCC. In vitro experimental measurements suggested that a combination of si-TACC3 and CDK1 inhibitor synergistically inhibited cell proliferation and migration, and induced G2 cell cycle arrest and apoptosis of HepG2 or MHCC97H cells. In conclusion, our results revealed a prospective dual-target, TACC3 and CDK1, therapeutic strategy to improve the treatment of HCC., (© 2023 Wiley Periodicals LLC.)

Oncolytic adenoviruses (OAds) present a promising path for cancer treatment due to their selectivity in infecting and lysing tumor cells and their ability to stimulate the immune response. In this study, we use an ordinary differential equation (ODE) model of tumor growth inhibited by oncolytic virus activity to parameterize previous research on the effect of genetically re-engineered OAds in A549 lung cancer tumors in murine models. We find that the data are best fit by a model that accounts for an immune response, and that the immune response provides a mechanism for elimination of the tumor. We also find that parameter estimates for the most effective OAds share characteristics, most notably a high infection rate and low viral clearance rate, that might be potential reasons for these viruses' efficacy in delaying tumor growth. Further studies observing E1A and P19 recombined viruses in different tumor environments may further illuminate the extent of the effects of these genetic modifications.

Bacillus proteases commonly exhibit remarkably reduced activity under cold conditions. Herein, we employed a tailored combination of a loop engineering strategy and iterative saturation mutagenesis method to engineer two loops for substrate binding at the entrance of the substrate tunnel of a protease (bcPRO) from Bacillus clausii to improve its activity under cold conditions. The variant MT6 (G95P/A96D/S99W/S101T/P127S/S126T) exhibited an 18.3-fold greater catalytic efficiency than the wild-type (WT) variant at 10 °C. Molecular dynamics simulations and dynamic tunnel analysis indicated that the introduced mutations extended the substrate-binding pocket volume and facilitated extra interactions with the substrate, promoting catalysis through binding in a more favorable conformation. This study provides insights and strategies relevant to improving the activities of proteases and supplies a novel protease with enhanced activity under cold conditions for the food industry to maintain the initial flavor and color of food and reduce energy consumption.

Deep learning based image enhancement models have largely improved the readability of fundus images in order to decrease the uncertainty of clinical observations and the risk of misdiagnosis. However, due to the difficulty of acquiring paired real fundus images at different qualities, most existing methods have to adopt synthetic image pairs as training data. The domain shift between the synthetic and the real images inevitably hinders the generalization of such models on clinical data. In this work, we propose an end-to-end optimized teacher-student framework to simultaneously conduct image enhancement and domain adaptation. The student network uses synthetic pairs for supervised enhancement, and regularizes the enhancement model to reduce domain-shift by enforcing teacher-student prediction consistency on the real fundus images without relying on enhanced ground-truth. Moreover, we also propose a novel multi-stage multi-attention guided enhancement network (MAGE-Net) as the backbones of our teacher and student network. Our MAGE-Net utilizes multi-stage enhancement module and retinal structure preservation module to progressively integrate the multi-scale features and simultaneously preserve the retinal structures for better fundus image quality enhancement. Comprehensive experiments on both real and synthetic datasets demonstrate that our framework outperforms the baseline approaches. Moreover, our method also benefits the downstream clinical tasks.

Background: Field notes, a form for resident-preceptor clinical encounter feedback, are widely adopted across Canadian medical residency training programs for documenting residents' performance. This process generates a sizeable cumulative collection of feedback text, which is difficult for medical education faculty to navigate. As sentiment analysis is a subfield of text mining that can efficiently synthesize the polarity of a text collection, sentiment analysis may serve as an innovative solution., Objective: This study aimed to examine the feasibility and utility of sentiment analysis using 3 popular sentiment lexicons on medical resident field notes., Methods: We used a retrospective cohort design, curating text data from University of Toronto medical resident field notes gathered over 2 years (from July 2019 to June 2021). Lexicon-based sentiment analysis was applied using 3 standardized dictionaries, modified by removing ambiguous words as determined by a medical subject matter expert. Our modified lexicons assigned words from the text data a sentiment score, and we aggregated the word-level scores to a document-level polarity score. Agreement between dictionaries was assessed, and the document-level polarity was correlated with the overall preceptor rating of the clinical encounter under assessment., Results: Across the 3 original dictionaries, approximately a third of labeled words in our field note corpus were deemed ambiguous and were removed to create modified dictionaries. Across the 3 modified dictionaries, the mean sentiment for the "Strengths" section of the field notes was mildly positive, while it was slightly less positive in the "Areas of Improvement" section. We observed reasonable agreement between dictionaries for sentiment scores in both field note sections. Overall, the proportion of positively labeled documents increased with the overall preceptor rating, and the proportion of negatively labeled documents decreased with the overall preceptor rating., Conclusions: Applying sentiment analysis to systematically analyze field notes is feasible. However, the applicability of existing lexicons is limited in the medical setting, even after the removal of ambiguous words. Limited applicability warrants the need to generate new dictionaries specific to the medical education context. Additionally, aspect-based sentiment analysis may be applied to navigate the more nuanced structure of texts when identifying sentiments. Ultimately, this will allow for more robust inferences to discover opportunities for improving resident teaching curriculums., (©Kevin Jia Qi Lu, Christopher Meaney, Elaine Guo, Fok-Han Leung. Originally published in JMIR Medical Education (https://mededu.jmir.org), 27.07.2023.)

Neutral π-radicals have potential for use as light emitters in optoelectronic devices due to the absence of energetically low-lying non-emissive states. Here, we report a defect-free synthetic methodology via mesityl substitution at the para-positions of tris(2,4,6-trichlorophenyl)methyl radical. These materials reveal a number of novel optoelectronic properties. Firstly, mesityl substituted radicals show strongly enhanced photoluminescence arising from symmetry breaking in the excited state. Secondly, photoexcitation of thin films of 8 wt% radical in 4,4'-bis(carbazol-9-yl)-1,1'-biphenyl host matrix produces long lived (in the order of microseconds) intermolecular charge transfer states, following hole transfer to the host, that can show unexpectedly efficient red-shifted emission. Thirdly, covalent attachment of carbazole into the mesitylated radical gives very high photoluminescence yield of 93% in 4,4'-bis(carbazol-9-yl)-1,1'-biphenyl films and light-emitting diodes with maximum external quantum efficiency of 28% at a wavelength of 689 nm. Fourthly, a main-chain copolymer of the mesitylated radical and 9,9-dioctyl-9H-fluorene shows red-shifted emission beyond 800 nm., (© 2023. The Author(s).)

Bone marrow mesenchymal stem cell (BMSC) transplantation is an effective treatment for ischemic heart disease, but its effectiveness is limited in aging populations due to decreased viability and injury resistance of autologous BMSCs. The purpose of this study was to compare the differences between platelet-rich plasma (PRP) derived from young and aged donors, and to investigate whether it is possible to enhance the viability of elderly human BMSCs (hBMSCs) using PRP, and to apply the rejuvenated hBMSCs for the treatment of ischemia. The key growth factors in PRP, including IGF-1, EGF, and PDGF-BB, were found to have significant differences between young and old individuals. Our results showed that PRP could enhance the proliferation, cloning, and rejuvenation of aged hBMSCs, with a superior effect observed when using PRP derived from younger donors. In the SD rat infarct model, the application of hBMSCs optimized with PRP resulted in a smaller infarct area compared to the control group (NC-Old). Specifically, the infarct area in the group treated with hBMSCs cultured with PRP from young donors (YPRP-Old) was smaller than that in the group treated with PRP from older donors (OPRP-Old). The survival rate of hBMSCs after transplantation, the number of neovascularization in the infarct area of SD rats and the recovery of cardiac function were all higher in the YPRP-Old group than the OPRP-Old group, and both groups were better than the group treated with aged hBMSCs alone. In conclusion, PRP may provide a new stem cell transplantation therapy option for ischemic diseases., Competing Interests: Declaration of competing interest All authors claim that there are no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Polychaetes are important benthic macrofauna that lives in sediments, usually in intertidal flats with high organic content and high sulfide. It has been suggested that polychaete bioturbation could perform environmental remediation. During the process, the microbial community plays important roles. Here, we used high-throughput sequencing technology to study the bioturbation effects on the bacterial community in the polychaete (Perinereis aibuhitensis) burrows at different tidal positions in intertidal flat. The results showed that the bacterial communities were dramatically influenced by the polychaete bioturbation. The ACE, Chao, and Shannon indices of the polychaete burrows increased in summer. Dominant phyla in the polychaete burrows were Proteobacteria, Campilobacterota, Desulfobacterota, Chloroflexi, and Bacteroidota, and the dominant bacterial families were Sulfurvaceae, Flavobacteriaceae, Rhodobacteraceae, Woeseiaceae, Desulfobulbaceae, and Sulfurimonadaceae. Results of linear discriminant analysis effect size (LEfSe) showed that groups that include organic matter degraders, such as Bacteroidota, Flavobacteriaceae, Rhodobacteraceae, Woeseiaceae, and groups that include sulfur oxidizers, such as Campilobacterota, Sulfurovaceae, Rhodobacteraceae, Desulfobulbaceae, and Sulfurimonadaceae, were significantly increased due to the polychaete bioturbation. The polychaete bioturbation reduced the complexity of the bacterial co-occurrence network while increased its modularity and homogeneity. The polychaete bioturbation also changed the functional groups, which significantly enhanced in functional groups of aerobic nitrite oxidation, nitration, dark thiosulfate oxidation, dark sulfur oxidation, and dark sulfite oxidation, while nitrogen respiration and nitrate respiration decreased. These results provide insight into the impact of bacterial communities under the intertidal polychaete bioturbation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pathological cardiac hypertrophy occurs in response to numerous increased afterload stimuli and precedes irreversible heart failure (HF). Therefore, therapies that ameliorate pathological cardiac hypertrophy are urgently required. Sirtuin 3 (Sirt3) is a main member of histone deacetylase class III and is a crucial anti-oxidative stress agent. Therapeutically enhancing the Sirt3 transfection efficiency in the heart would broaden the potential clinical application of Sirt3. Ultrasound-targeted microbubble destruction (UTMD) is a prospective, noninvasive, repeatable, and targeted gene delivery technique. In the present study, we explored the potential and safety of UTMD as a delivery tool for Sirt3 in hypertrophic heart tissues using adult male Bama miniature pigs. Pigs were subjected to ear vein delivery of human Sirt3 together with UTMD of cationic microbubbles (CMBs). Fluorescence imaging, western blotting, and quantitative real-time PCR revealed that the targeted destruction of ultrasonic CMBs in cardiac tissues greatly boosted Sirt3 delivery. Overexpression of Sirt3 ameliorated oxidative stress and partially improved the diastolic function and prevented the apoptosis and profibrotic response. Lastly, our data revealed that Sirt3 may regulate the potential transcription of catalase and MnSOD through Foxo3a. Combining the advantages of ultrasound CMBs with preclinical hypertrophy large animal models for gene delivery, we established a classical hypertrophy model as well as a strategy for the targeted delivery of genes to hypertrophic heart tissues. Since oxidative stress, fibrosis and apoptosis are indispensable in the evolution of cardiac hypertrophy and heart failure, our findings suggest that Sirt3 is a promising therapeutic option for these diseases. STATEMENT OF SIGNIFICANCE: Pathological cardiac hypertrophy is a central prepathology of heart failure and is seen to eventually precede it. Feasible targets that may prevent or reverse disease progression are scarce and urgently needed. In this study, we developed surface-filled lipid octafluoropropane gas core cationic microbubbles that could target the release of human Sirt3 reactivating the endogenous Sirt3 in hypertrophic hearts and protect against oxidative stress in a pig model of cardiac hypertrophy induced by aortic banding. Sirt3-CMBs may enhance cardiac diastolic function and ameliorate fibrosis and apoptosis. Our work provides a classical cationic lipid-based, UTMD-mediated Sirt3 delivery system for the treatment of Sirt3 in patients with established cardiac hypertrophy, as well as a promising therapeutic target to combat pathological cardiac hypertrophy., Competing Interests: Declaration of Competing Interest All authors declare no known competing financial interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Tetracyclic oxindole alkaloids (TOAs), main active ingredients of Uncaria rhynchophylla (UR), has inspired the interest of pharmacologists and chemists because of its great potential in the treatment of the diseases of the nervous system and cardiovascular system and its special spirooxindole scaffold, but the biosynthetic pathway of this compounds is still unknown. In this work, the metabolomics and transcriptomics of hook, leaf and stem of UR were analyzed, and 31 alkaloids and 47,423 unigenes were identified, as well as the relative contents of these alkaloids were evaluated. Based on the above results and literatures, a proposal biosynthetic pathway for TOAs was devised. Furthermore, three unigenes were suggested mediating the biosynthesis of TOAs through the integrated analysis of metabolomics and transcriptomics, and three enzymes, tryptophan decarboxylase, strictosidine synthase and strictosidine-β-d-glucosidase, were identified as important catalytic enzymes for the synthesis of tryptamine, strictosidine (7) and 4,21-dehydrogeissochizine, respectively, which are considered as the important precursors of TOAs., 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 Inc.)

Setaria italica (foxtail millet), a founder crop of East Asian agriculture, is a model plant for C4 photosynthesis and developing approaches to adaptive breeding across multiple climates. Here we established the Setaria pan-genome by assembling 110 representative genomes from a worldwide collection. The pan-genome is composed of 73,528 gene families, of which 23.8%, 42.9%, 29.4% and 3.9% are core, soft core, dispensable and private genes, respectively; 202,884 nonredundant structural variants were also detected. The characterization of pan-genomic variants suggests their importance during foxtail millet domestication and improvement, as exemplified by the identification of the yield gene SiGW3, where a 366-bp presence/absence promoter variant accompanies gene expression variation. We developed a graph-based genome and performed large-scale genetic studies for 68 traits across 13 environments, identifying potential genes for millet improvement at different geographic sites. These can be used in marker-assisted breeding, genomic selection and genome editing to accelerate crop improvement under different climatic conditions., (© 2023. The Author(s).)

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma. The prognosis for patients with ccRCC has improved over recent years with the use of combination therapies with an anti-programmed death-1 (PD-1) backbone. This has enhanced the quality of life and life expectancy of patients with this disease. Unfortunately, not all patients benefit; eventually, most patients will develop resistance to therapy and progress. Recent molecular, biochemical, and immunological research has extensively researched anti-angiogenic and immune-based treatment resistance mechanisms. This analysis offers an overview of the principles underpinning the resistance pathways related to immune checkpoint inhibitors (ICIs). Additionally, novel approaches to overcome resistance that may be considered for the trial context are discussed., Competing Interests: All authors declared that there are no conflicts of interest., (© The Author(s) 2023.)

Efficient and robust non-platinum-group metal electrocatalysts for O 2 reduction are a prerequisite for practical high-performance fuel cells and metal-air batteries. Herein, we reported an integrated principle of gradient electrospinning and controllable pyrolysis to fabricate various Co-doped Ni 3 V 2 O 8 nanofibers with high oxygen reduction reaction (ORR) activity. The representative Co 1.3 Ni 1.7 V 2 O 8 nanofibers showed outstanding ORR performance in an alkaline solution with a half-wave potential ( E 1/2 ) of 0.874 V vs RHE, along with high long-term stability. Furthermore, the introduction of Co could effectively restrain the growth of nanoparticles and change the electronic structure of Ni 3 V 2 O 8 . Control experiments and theoretical calculations demonstrated that upon Co-doping, the hybridization between the 3d orbital for both Co and Ni guaranteed the stable adsorption interaction with O 2 over Ni and Co metal centers. Meanwhile, the weakened binding ability of Ni 3 V 2 O 8 to OH* reduced the ORR free energy. Overall, the synergistic effect of Co and Ni metal cations essentially reflected the origin of ORR activity on the Co-doped Ni 3 V 2 O 8 nanofibers. This work offers new insights and practical guidance for designing highly active ORR catalysts for electrochemical clean energy conversion and storage.

Optical imaging through scattering media is a practical challenge with crucial applications in many fields. Many computational imaging methods have been designed for object reconstruction through opaque scattering layers, and remarkable recovery results have been demonstrated in the physical models or learning models. However, most of the imaging approaches are dependent on relatively ideal states with a sufficient number of speckle grains and adequate data volume. Here, the in-depth information with limited speckle grains has been unearthed with speckle reassignment and a bootstrapped imaging method is proposed for reconstruction in complex scattering states. Benefiting from the bootstrap priors-informed data augmentation strategy with a limited training dataset, the validity of the physics-aware learning method has been demonstrated and the high-fidelity reconstruction results through unknown diffusers are obtained. This bootstrapped imaging method with limited speckle grains broadens the way to highly scalable imaging in complex scattering scenes and gives a heuristic reference to practical imaging problems.

Objective: The main purpose of this study is to perform a comprehensive investigation of the prognostic value and molecular mechanism of syntaxin binding protein 5 antisense RNA 1 (STXBP5-AS1) through the whole genome RNA sequencing data of the The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) cohort. Methods: There were 438 COAD patients were fit into current study for survival analysis. Gene expression profiling interactive analysis 2.0, Database for Annotation, Visualization and Integrated Discovery v6.8, gene set enrichment analysis (GSEA) and connectivity map (CMap) are used to investigate the molecular mechanisms and targeted drugs of STXBP5-AS1 in COAD. Results: By comparing the expression level of tumor and non-tumor tissues, we found that STXBP5-AS1 was notablely down-regulated in COAD tumor tissues. Survival analysis suggested that low STXBP5-AS1 expression was significantly related to poor overall survival (OS) of COAD (log-rank P=0.035, adjusted P=0.005, HR=0.545, 95%CI=0.356-0.836). The enrichment analysis of STXBP5-AS1 co-expressed genes, GSEA and differentially expressed genes suggests that STXBP5-AS1 may play a part in COAD by regulating the following biological processes or pathways: cell junction, DNA replication, apoptosis, cell cycle, metastasis, tumor protein 53, Wnt, mTORC1, MCM, notch receptor 4, transforming growth factor beta receptor, and cGMP-PKG signaling pathway. CMap analysis was screened out four small molecule drugs (anisomycin, cephaeline, NU-1025 and quipazine) that may be used as STXBP5-AS1 targeted therapy drugs in COAD. The co-expression analysis of STXBP5-AS1 and immune cell gene signature indicated that STXBP5-AS1 was significantly related to immune cell gene set in normal intestinal tissues, but not in COAD tumor tissues. Conclusion: Our results revealed that STXBP5-AS1 is notablely down-regulated in COAD tumor tissues, and may act as a novel prognostic biomarker for COAD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Strengthening Mg alloys with rare earth elements has been a research focus for several decades. To minimize the usage of rare earth elements while enhancing mechanical properties, we adopted the strategy of alloying with multiple rare earth elements, namely Gd, Y, Nd, and Sm. Additionally, to promote the precipitation of basal precipitate, Ag and Zn doping was also induced. Thus, we designed a new cast Mg-2Gd-2Y-2Nd-2Sm-1Ag-1Zn-0.5Zr (wt.%) alloy. The microstructure of the alloy and its relevance to mechanical properties in various heat treatment conditions were investigated. After undergoing a heat treatment process, the alloy demonstrated exceptional mechanical properties, with a yield strength of 228 MPa and an ultimate tensile strength of 330 MPa achieved through peak-aging for 72 h at 200 °C. The excellent tensile properties are due to the synergistic effect of basal γ″ precipitate and prismatic β' precipitate. In its as-cast state, its primary mode of fracture is inter-granular, whereas in the solid-solution and peak-aging conditions, the predominant mode of fracture is a mixture of trans-granular and inter-granular fractures.

Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer of the cells lining the pleural cavity with a low overall incidence. The National Cancer Database (NCDB) released in August 2022 updated data that reflect the newest trends in MPM., Methods: The NCDB was queried for patients diagnosed with MPM between 2004 and 2020. Variables collected included demographics, tumor characteristics, and treatment. Student's t-test and independent-samples proportions test were used for means analysis. Survival was assessed by the Kaplan-Meier method using SPSS version 28., Results: A total of 41,074 patients were diagnosed with mesothelioma, with a steady incidence (0.25%) between 2004 and 2017. The mean age of diagnosis was 70 (SD 13). 73.2% of the patients were males, 69% had no comorbidities, and 93.3% were white. More patients were diagnosed at Stage 1 after 2008 (p < 0.001). Since 2010, there has been a significant increase in patients offered treatment with 73.9% receiving some therapy (p < 0.01): 50.5% received chemotherapy, 27.6% surgery, 8.6% radiation, and 5.4% immunotherapy. The median overall survival was 10.3 months from diagnosis [95% CI: 10.2-10.5]. Risk factors associated with 30-day mortality from surgical intervention included age (OR = 1.02, p < 0.001), male gender (OR = 1.3, p = 0.03), poorly differentiated grade (OR = 2.1, p < 0.001), Stage 4 (OR = 1.4, p = 0014), and epithelioid histology (OR = 0.51, p = 0.03)., Conclusion: The current management of MPM is based on stage and histologic subtype. Due to the small numbers of patients at most academic centers, the NCDB provides a robust dataset to draw upon broad data points in treatment discussions with patients., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The process performance of partial denitrification of a novel anaerobic fermentation integrated fixed-film activated sludge (IFAS-AFPD) of Enteromorpha was studied. The response surface method was used to determine the optimal reaction conditions, and the operation experiment was carried out under the optimal conditions. The results showed that the nitrogen removal effect was the best when the salinity was 12.2 g•L -1 , the Carbon-Nitrogen ratio (C/N) was 4, the pH was 8.5, and the Nitrite Accumulation Rate, Nitrate Removal Rate, Chemical Oxygen Demand Utilization Rate could reach 77%, 89% and 51%. Experimental results have shown that the NAR of the Enteromorpha ferment liquid system could be maintained at about 74%, which was noteworthy higher than that of the sodium acetate (CH 3 COONa) system at 42%; Microbial community analysis showed that Enteromorpha ferment liquid was more beneficial to the growth of Bacteroidetes than CH 3 COONa., 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.)

The electrocatalytic nitrogen reduction reaction (NRR) to synthesize NH 3 under ambient conditions is a promising alternative route to the conventional Haber-Bosch process, but it is still a great challenge to develop electrocatalysts' high Faraday efficiency and ammonia yield. Herein, a facile and efficient exfoliation strategy to synthesize ultrathin 2D boron and nitrogen co-doped porous carbon nanosheets (B/NC NS) via a metal-organic framework (MOF)-derived van der Waals superstructure, is reported. The results of experiments and theoretical calculations show that the doping of boron and nitrogen can modulate the electronic structure of the adjacent carbon atoms; which thus, promotes the competitive adsorption of nitrogen and reduces the energy required for ammonia synthesis. The B/NC NS exhibits excellent catalytic performance and stability in electrocatalytic NRR, with a yield rate of 153.4 µg·h -1 ·mg -1 cat and a Faraday efficiency of 33.1%, which is better than most of the reported NRR electrocatalysts. The ammonia yield of B/NC NS can maintain 92.7% of the initial NRR activity after 48 h stability test. The authors' controllable exfoliation strategy using MOF-derived van der Waals superstructure can provide a new insight for the synthesis of other 2D materials., (© 2023 Wiley-VCH GmbH.)

Strengthening the CoCrFeNi high entropy alloy with a face-center cubic structure has become a research prospect in the last decade. Alloying with double elements, Nb and Mo, is an effective method. In this paper, to further enhance the strength of the Nb and Mo contained high entropy alloy, CoCrFeNiNb 0.2 Mo 0.2 was annealing treated at different temperatures for 24 h. As a result, a new kind of Cr 2 Nb type nano-scale precipitate with a hexagonal close-packed structure was formed, which is semi-coherent with the matrix. Moreover, by adjusting the annealing temperature, the precipitate was tailored with a considerable quantity and fine size. The best overall mechanical properties were achieved in the alloy annealed at 700 °C. The yield strength, ultimate tensile strength, and elongation are 727 MPa, 1.05 GPa, and 8.38%, respectively. The fracture mode of the annealed alloy is a mixture of cleavage and necking-featured ductile fracture. The approach employed in this study offers a theoretical foundation for enhancing the mechanical properties of face-centered cubic high entropy alloys via annealing treatment.

Objective: Risk perception, a critical psychological construct, influences health behavior modification and maintenance of individuals with cardiovascular disease (CVD) risk. Little is known about CVD risk perception among Chinese adults. This research examined the profiles of CVD risk perception of community adults in South China, and explored the characteristics and factors that influence their perception of CVD risk., Method: This cross-sectional study was conducted in Hangzhou, Zhejiang Province, in South China from March to July 2022 and included 692 participants. Risk perception was assessed using the Chinese version of the Attitude and Beliefs about Cardiovascular Disease Risk Questionnaire. Latent profile analysis (LPA) was performed to extract latent classes of CVD risk perception. These classes of CVD risk perception were compared with 10-year CVD risk categories to define correctness of estimation. Chi-square tests and multinomial regression analyses were used to identify differences between these categories., Results: Three CVD risk perception classes were identified by LPA: low risk perception (14.2% of participants), moderate risk perception (46.8%), high risk perception (39.0%). Individuals who were aged with 40-60 year ( OR = 6.94, 95% CI = 1.86-25.84), diabetes ( OR = 6.26, 95% CI = 1.34-29.17), married ( OR = 4.52, 95% CI = 2.30-8.90), better subjective health status ( OR = 3.23, 95% CI = 1.15-9.10) and perceived benefits and intention to change physical activity ( OR = 1.16, 95% CI = 1.05-1.27) were more likely to be in the high-risk perception class. Compared to absolute 10-year CVD risk based on China-PAR, a third of participants (30.1%) correctly estimated their CVD risk, 63.3% overestimated it and 6.6% underestimated it. CVD risk underestimation was associated with hypertension ( OR = 3.91, 95% CI = 1.79-8.54), drinking ( OR = 3.05, 95% CI = 1.22-7.64), better subjective health status ( OR = 2.67, 95% CI = 1.18-6.03)., Conclusions: Most adults in South China possess a moderate level of CVD risk perception. Advanced age, higher monthly income, diabetes and better health status were significantly related to higher perceived CVD risk. Individuals with hypertension, drinking and better subjective health status were associated with CVD risk underestimation. Healthcare professionals should pay attention to the indicators for different classes and identify underestimation group as early as possible., Competing Interests: YY was employed by China Mobile (Hangzhou) Information Technology Co., Ltd. The remaining 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 Guo, Yuan, Fu, Cui, Yu, Guo, Ding, Zhang and Jin.)

Cancer-associated fibroblasts (CAFs) are heterogeneous stromal cells present in the tumor microenvironment (TME), which play a critical role in gastric cancer (GC) progression. Here, we examined a subset of CAFs with high podoplanin (PDPN) expression, which is correlated with tumor metastasis and poor survival in GC patients. Animal models of gastric cancer liver metastasis monitored by micro-PET/CT confirmed that periostin (POSTN) derived from PDPN(+) CAFs regulated CAFs' pro-migratory ability. Mechanistically, PDPN(+) CAFs secreted POSTN to modulate cancer stem cells (CSCs) through FAK/AKT phosphorylation. Furthermore, POSTN could also activate FAK/YAP signaling in GC cells to produce increased amounts of IL-6, which in turn induced phosphorylation of PI3K/AKT in PDPN(+) CAFs. Prolonged PI3K/AKT pathway activation in PDPN(+) CAFs maintains the production of POSTN and the effect on CSC enrichment and GC cell migration. In conclusion, our study demonstrated a positive feedback loop between PDPN(+) CAFs and CSCs during GC progression and suggested a selective target for GC treatment., (© 2023 Wiley Periodicals LLC.)

Magnetoelectric coupling, as a fundamental physical nature and with the potential to add functionality to devices while also reducing energy consumption, has been challenging to be probed in freestanding membranes or two-dimensional materials due to their instability and fragility. In this paper, we report a magnetoelectric coupling probed by optical second harmonic generation with external magnetic field, and show the manipulation of the ferroelectric and antiferromagnetic orders by the magnetic and thermal fields in BiFeO 3 films epitaxially grown on the substrates and in the freestanding ones. Here we define an optical magnetoelectric-coupling constant, denoting the ability of controlling light-induced nonlinear polarization by the magnetic field, and found the magnetoelectric-coupling was suppressed by strain releasing but remain robust against thermal fluctuation for freestanding BiFeO 3 ., (© 2023. The Author(s).)

We present JBrowse 2, a general-purpose genome annotation browser offering enhanced visualization of complex structural variation and evolutionary relationships. It retains core features of JBrowse while adding new views for synteny, dotplots, breakpoints, gene fusions, and whole-genome overviews. It allows users to share sessions, open multiple genomes, and navigate between views. It can be embedded in a web page, used as a standalone application, or run from Jupyter notebooks or R sessions. These improvements are enabled by a ground-up redesign using modern web technology. We describe application functionality, use cases, performance benchmarks, and implementation notes for web administrators and developers., (© 2023. The Author(s).)

Background: Cerebrospinal fluid (CSF) pathogen culture suffers from the drawbacks of prolonged cycle time and a low positivity rate in diagnosing intracranial infections in children. This study aims to investigate the diagnostic potential of targeted next-generation sequencing (tNGS) in pediatric neurosurgery for central nervous system (CNS) infections., Methods: A retrospective study was conducted on children under 14 with suspected intracranial infections following craniocerebral trauma or surgery between November 2018 and August 2020. Routine, biochemical, smear, and pathogen culture tests were performed on CSF during treatment. The main parameters of CSF analysis encompassed white blood cells (WBC, ×10 6 /L) count, percentage of multinucleated cells (%), protein levels (g/L), glucose concentration (GLU, mmol/L), chloride levels (mmol/L), and pressure (mmH2O). The outcomes of tNGS were assessed through the Receiver Operating Characteristic (ROC) curve and pertinent diagnostic parameters., Results: Among the 35 included pediatric patients, 22 were clinically diagnosed with CNS infection in neurosurgery, tNGS was confirmed in 18 cases. The sensitivity and specificity of tNGS were 81.8% and 76.9%, respectively, while the traditional method of CSF cultures and smears exhibited a sensitivity of 13.6% and a specificity of 100%. ROC curve analysis indicated an area under the curve (AUC) of 0.794 for tNGS and 0.568 for the CSF cultures and smears. CSF analysis indicated that the two groups exhibited statistically significant differences in terms of WBC count [330.0 (110.00-2639.75) vs 14.00 (4.50-26.50), P<0.001] and percentage of multinuclear cells (%) [87.50 (39.75-90.00) vs 0 (0-10.00), P<0.001]. However, the remaining parameters did not statistically significant differences between the groups (all P>0.05)., Conclusion: tNGS demonstrates a high degree of diagnostic accuracy when detecting infections within the CNS of pediatric neurosurgery patients. tNGS can effectively establish for diagnosing CNS infections by detecting pathogenic microorganisms and their corresponding virulence and/or resistance genes within the test samples., Competing Interests: The authors declare that they have no conflicts of interest., (© 2023 Li et al.)

Background: Mismatch repair deficiency (dMMR) is a well-recognized biomarker for response to immune checkpoint blockade (ICB). Strategies to convert MMR-proficient (pMMR) to dMMR phenotype with the goal of sensitizing tumors to ICB are highly sought. The combination of bromodomain containing 4 (BRD4) inhibition and ICB provides a promising antitumor effect. However, the mechanisms underlying remain unknown. Here, we identify that BRD4 inhibition induces a persistent dMMR phenotype in cancers., Methods: We confirmed the correlation between BRD4 and mismatch repair (MMR) by the bioinformatic analysis on The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium data, and the statistical analysis on immunohistochemistry (IHC) scores of ovarian cancer specimens. The MMR genes (MLH1,MSH2,MSH6,PMS2) were measured by quantitative reverse transcription PCR, western blot, and IHC. The MMR status was confirmed by whole exome sequencing, RNA sequencing, MMR assay and hypoxanthine-guanine phosphoribosyl transferase gene mutation assay. The BRD4i AZD5153 resistant models were induced both in vitro and in vivo. The transcriptional effects of BRD4 on MMR genes were investigated by chromatin immunoprecipitation among cell lines and data from the Cistrome Data Browser. The therapeutic response to ICB was testified in vivo. The tumor immune microenvironment markers, such as CD4, CD8, TIM-3, FOXP3, were measured by flow cytometry., Results: We identified the positive correlation between BRD4 and MMR genes in transcriptional and translational aspects. Also, the inhibition of BRD4 transcriptionally reduced MMR genes expression, resulting in dMMR status and elevated mutation loads. Furthermore, prolonged exposure to AZD5153 promoted a persistent dMMR signature both in vitro and in vivo, enhancing tumor immunogenicity, and increased sensitivity to α-programmed death ligand-1 therapy despite the acquired drug resistance., Conclusions: We demonstrated that BRD4 inhibition suppressed expression of genes critical to MMR, dampened MMR, and increased dMMR mutation signatures both in vitro and in vivo, sensitizing pMMR tumors to ICB. Importantly, even in BRD4 inhibitors (BRD4i)-resistant tumor models, the effects of BRD4i on MMR function were maintained rendering tumors sensitive to ICB. Together, these data identified a strategy to induce dMMR in pMMR tumors and further, indicated that BRD4i sensitive and resistant tumors could benefit from immunotherapy., Competing Interests: Competing interests: GBM is one of the SAB (Scientific Advisory Board) members or consults with AstraZeneca, Chrysallis Biotechnology, GSK, ImmunoMET, Ionis, Lilly, PDX Pharmaceuticals, Signalchem Lifesciences, Symphogen, Tarveda, Turbine, Zentalis Pharmaceuticals. GBM has stock options with Catena Pharmaceuticals, ImmunoMet, SignalChem, Tarveda., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We previously developed a polysaccharide--RBD-conjugated nanoparticle vaccine which induced protective efficacy against SARS-CoV-2 in a mouse model. Here, we newly developed a vaccine, SCTV01A, by chemically conjugating recombinant SARS-CoV-2 RBD-Fc and PPS14 ( Streptococcus pneumoniae serotype type 14 capsular polysaccharide). The immunogenicity and toxicity of SCTV01A were evaluated in animal models. The PPS14 conjugation enhanced the immunogenicity of RBD-Fc in C57BL/6 mice whether formulated with SCT-VA02B or Alum adjuvant. SCTV01A also induced high opsonophagocytic activity (OPA) against S. pneumoniae serotype 14. In addition, SCTV01A stimulated potent neutralizing titers in rhesus macaques and effectively reduced lung inflammation after SARS-CoV-2 infection with neither antibody-dependent enhancement (ADE) nor vaccine-enhanced diseases (VED) phenomenon. Importantly, the long-term toxicity study of SCTV01A in rhesus macaques did not cause any abnormal toxicity and was tolerated at the highest tested dose (120 μg). The existing immunogenicity and toxicological evaluation results have demonstrated the safety and efficacy of SCTV01A, which will be a promising and feasible vaccine to protect against SARS-CoV-2 infection.

The thermal conductivity of superlattices is strongly reduced as compared to that of the parent materials due to phonon-scattering and thermal boundary resistances at the superlattice period interfaces. Herein, homogenous superlattices consisting of homogenous structural Ce δ Ca 1- δ TiO 3 and CaTi 1- δ Ce δ O 3 alternate layers were obtained through a variable-valence Ce doping, providing multi-quantum well interfaces between the alternate layers due to Ce-substitution at Ca and Ti sites, respectively. This material comprising these homogenous superlattices displayed a significantly reduced lattice thermal conductivity of 1.82 W m -1 K -1 and a record high zT value of 0.405 at 1031 K in CaTiO 3 -based thermoelectric materials. This strategy of synthesizing homogeneous superlattices provides a cost advantage over heterogeneous superlattices prepared by the molecular beam epitaxy method and paves a route for preparing bulk superlattices with unique thermoelectric properties rooting in the quantum domain limiting effect.

Ovarian cancer (OC) ranks first among gynecologic malignancies in terms of mortality. The benefits of poly (ADP-ribose) polymerase (PARP) inhibitors appear to be limited to OC with BRCA mutations. Concurrent administration of WEE1 inhibitors (eg, adavosertib (Ada)) and PARP inhibitors (eg, olaparib (Ola)) effectively suppress ovarian tumor growth regardless of BRCA mutation status, but is poorly tolerated. Henceforth, we aimed to seek a strategy to reduce the toxic effects of this combination by taking advantage of the mesoporous polydopamine (MPDA) nanoparticles with good biocompatibility and high drug loading capacity. In this work, we designed a tumor-targeting peptide TMTP1 modified MPDA-based nano-drug delivery system (TPNPs) for targeted co-delivery of Ada and Ola to treat OC. Ada and Ola could be effectively loaded into MPDA nanoplatform and showed tumor microenvironment triggered release behavior. The nanoparticles induced more apoptosis in OC cells, and significantly enhanced the synergy of combination therapy with Ada plus Ola in murine OC models. Moreover, the precise drug delivery of TPNPs towards tumor cells significantly diminished the toxic side effects caused by concurrent administration of Ada and Ola. Co-delivery of WEE1 inhibitors and PARP inhibitors via TPNPs represents a promising approach for the treatment of OC. STATEMENT OF SIGNIFICANCE: Combination therapy of WEE1 inhibitors (eg, Ada) with PARP inhibitors (eg, Ola) effectively suppress ovarian tumor growth regardless of BRCA mutation status. However, poor tolerability limits its clinical application. To address this issue, we construct a tumor-targeting nano-drug delivery system (TPNP) for co-delivery of Ada and Ola. The nanoparticles specifically target ovarian cancer and effectively enhance the antitumor effect while minimizing undesired toxic side effects. As the first nanomedicine co-loaded with a WEE1 inhibitor and a PARP inhibitor, TPNP-Ada-Ola may provide a promising and generally applicable therapeutic strategy for ovarian cancer patients., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Postmenopausal osteoporosis (PMOP) is a common bone disease characterized by decreased bone density and increased bone fragility due to decreased estrogen levels. Qiangguyin (QGY) is transformed from the famous traditional Chinese medicine BuShen Invigorating Blood Decoction. In this study, we used QGY to treat PMOP. We observed that QGY significantly reduced fat accumulation in the chondro-osseous junction. However, its specific mechanism of action remains unclear. To determine the specific molecular mechanism of QGY, we explored the pharmacological mechanism by which QGY reduces fat accumulation in the chondro-osseous junction through network pharmacological analysis. The active components and targets related to PMOP and QGY were screened from different databases, forming a composition-target-disease network. Next, a comprehensive analysis platform including protein-protein interaction (PPI) network, Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were established. The results revealed that QGY inhibits adipogenic differentiation by activating the mitogen-activated protein kinase (MAPK) signaling pathway, thus reducing the accumulation of fat in the chondro-osseous junction. For further verification. In vitro and in vivo experiments were carried out. Our data showed that QGY significantly reversed the high expression of fatty acid binding protein 4 (FABP4) and peroxisome proliferator-activated receptor γ (PPARγ). Further, QGY prevents fat accumulation by inhibiting the expression of p38. In summary, the results of this study suggested that QGY-induced phenotypic changes are related to the activation of the p38 MAPK signaling pathway., Competing Interests: Conflict of interest statement 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Quantifying the severity of head shape deformity and establishing a threshold for operative intervention remains challenging in patients with metopic craniosynostosis (MCS). This study combines three-dimensional skull shape analysis with an unsupervised machine-learning algorithm to generate a quantitative shape severity score (cranial morphology deviation) and provide an operative threshold score., Methods: Head computed tomography scans from subjects with MCS and normal controls (5 to 15 months of age) were used for objective three-dimensional shape analysis using ShapeWorks software and in a survey for craniofacial surgeons to rate head-shape deformity and report whether they would offer surgical correction based on head shape alone. An unsupervised machine-learning algorithm was developed to quantify the degree of shape abnormality of MCS skulls compared to controls., Results: One hundred twenty-four computed tomography scans were used to develop the model; 50 (24% MCS, 76% controls) were rated by 36 craniofacial surgeons, with an average of 20.8 ratings per skull. The interrater reliability was high (intraclass correlation coefficient, 0.988). The algorithm performed accurately and correlates closely with the surgeons assigned severity ratings (Spearman correlation coefficient, r = 0.817). The median cranial morphology deviation for affected skulls was 155.0 (interquartile range, 136.4 to 194.6; maximum, 231.3). Skulls with ratings of 150.2 or higher were very likely to be offered surgery by the experts in this study., Conclusions: This study describes a novel metric to quantify the head shape deformity associated with MCS and contextualizes the results using clinical assessments of head shapes by craniofacial experts. This metric may be useful in supporting clinical decision making around operative intervention and in describing outcomes and comparing patient population across centers., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Two-dimensional ferromagnetic Weyl half-metals that are robust against spin-orbital coupling were theoretically proposed recently, in which the nodal points and the nodal loops are protected by specific symmetries. As the symmetry of a ferromagnetic material is highly dependent on the magnetization orientation, here we predict a family of two-dimensional ferromagnetic Weyl half-metals, Mn 2 X 3 (X = S, Se, Te) monolayers, to investigate the band topology under different magnetization orientations in the presence of spin-orbital coupling. The Curie temperatures (∼1000 K) were estimated to be much higher than room temperature due to the strong double exchange interaction and the suppression of spin fluctuation for the two-sublayer structure. Taking a Mn 2 Te 3 monolayer as an example, we demonstrated the evolution of the nodal points and the nodal loops in the presence of spin-orbital coupling via manipulating magnetization orientation. Our work provides a family of high temperature two-dimensional ferromagnetic Weyl half-metals for investigating the nontrivial band topology.

Cervical cancer (CC) that is caused by high-risk human papillomavirus (HPV) remains a significant public health problem worldwide. HPV integration sites can be silent or actively transcribed, leading to the production of viral-host fusion transcripts. Herein, we demonstrate that only productive HPV integration sites were nonrandomly distributed across both viral and host genomes, suggesting that productive integration sites are under selection and likely to contribute to CC pathophysiology. Furthermore, using large-scale, multi-omics (clinical, genomic, transcriptional, proteomic, phosphoproteomic, and single-cell) data, we demonstrate that tumors with productive HPV integration are associated with higher E6/E7 proteins and enhanced tumor aggressiveness and immunoevasion. Importantly, productive HPV integration increases from carcinoma in situ to advanced disease. This study improves our understanding of the functional consequences of HPV fusion transcripts on the biology and pathophysiology of HPV-driven CCs, suggesting that productive HPV integration should be evaluated as an indicator of high risk for progression to aggressive cancers., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Motivation: JBrowse Jupyter is a package that aims to close the gap between Python programming and genomic visualization. Web-based genome browsers are routinely used for publishing and inspecting genome annotations. Historically they have been deployed at the end of bioinformatics pipelines, typically decoupled from the analysis itself. However, emerging technologies such as Jupyter notebooks enable a more rapid iterative cycle of development, analysis and visualization., Results: We have developed a package that provides a Python interface to JBrowse 2's suite of embeddable components, including the primary Linear Genome View. The package enables users to quickly set up, launch and customize JBrowse views from Jupyter notebooks. In addition, users can share their data via Google's Colab notebooks, providing reproducible interactive views., Availability and Implementation: JBrowse Jupyter is released under the Apache License and is available for download on PyPI. Source code and demos are available on GitHub at https://github.com/GMOD/jbrowse-jupyter., (© The Author(s) 2023. Published by Oxford University Press.)

Introduction: The anti-angiogenic agent vascular endothelial growth factor 165b (VEGF165b) mutant (mVEGF165b), which was developed by our laboratory, has superior antitumor activity to that of native VEGF165b; however, its mechanism of action and druggability need further exploration., Methods: Using the commercial anti-angiogenic drug bevacizumab as a positive control, the mechanism and developability of mVEGF165b were evaluated and explored. The Cell Counting Kit-8 assay was performed to evaluate the effects of mVEGF165b and bevacizumab alone on the proliferation of human umbilical vein endothelial cells (HUVECs). Meanwhile, the inhibitory effects of mVEGF165b and bevacizumab combined with paclitaxel in a mouse model of breast cancer were assessed. Immunohistochemistry was used to detect their effects on tumor vascular maturation, and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to detect the apoptosis of tumor cells., Results: In vitro cell experiments confirmed that mVEGF165b inhibited the proliferation of HUVECs with an efficacy equivalent to that of bevacizumab. mVEGF165b and bevacizumab combined with paclitaxel significantly delayed the growth of breast cancer in mice. Immunohistochemistry and the TUNEL assay showed that mVEGF165b and bevacizumab combined with paclitaxel-induced higher vascular maturity and more apoptosis than paclitaxel alone., Conclusion: mVEGF165b showed similar efficacy and mechanism of action as bevacizumab, indicating its potential to be developed into a safe and effective anti-angiogenic drug., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)