The role of biophysical cues and their modulated exosomes in dental diseases: from mechanism to therapy.

Dental diseases such as caries and periodontitis have been common public health problems. Dental disease treatment can be achieved through stem cell-based dental regeneration. Biophysical cues determine the fate of stem cells and govern the success of dental regeneration. Some studies have manifested exosomes derived from stem cells could not only inherit biophysical signals in microenvironment but also evade some issues in the treatment with stem cells. Nowadays, biophysical cue-regulated exosomes become another promising therapy in dental regenerative medicine. However, methods to improve the efficacy of exosome therapy and the underlying mechanisms are still unresolved. In this review, the association between biophysical cues and dental diseases was summarized. We retrospected the role of exosomes regulated by biophysical cues in curing dental diseases and promoting dental regeneration. Our research also delved into the mechanisms by which biophysical cues control the biogenesis, release, and uptake of exosomes, as well as potential methods to enhance the effectiveness of exosomes. The aim of this review was to underscore the important place biophysical cue-regulated exosomes occupy in the realm of dentistry, and to explore novel targets for dental diseases.

The Optimal First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer Based on Liver Metastasis Status: A Network Meta-Analysis and Systematic Review.

PURPOSE: To compare the efficacy of first-line regimens based on programmed cell death (or ligand) [PD-(L)1] blockade in extensive-stage small-cell lung cancer (ES-SCLC) patients with or without liver metastases (LM), and to identify optimal treatment strategies. METHODS: Network meta-analysis of randomized controlled trials (RCTs) comparing chemo-immunotherapy (CIT) and chemotherapy (CT) in ES-SCLC patients stratified by LM. Overall survival (OS) and progression-free survival (PFS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Seven RCTs involving 3658 ES-SCLC patients (1243 with LM, 2415 without LM) were analyzed. For patients with LM, the combination therapies of anti-PD-1 + CT (HR, 0.67; 95% CI, 0.54%-0.82%; p < 0.001) and anti-PD-L1 + CT + anti-angiogenesis (HR, 0.84; 95% CI, 0.71%-0.99%; p = 0.042) demonstrated superior efficacy in prolonging OS compared to CT alone. The anti-PD-1 + CT regimen had the highest cumulative probability of 91.6% for extending OS in patients with LM. For patients without LM, all CIT regimens resulted in improved OS compared to CT alone, with the regimen of anti-angiogenesis + anti-PD-L1 + CT ranking first and having the highest cumulative probability of 95.5% for prolonging OS. CONCLUSIONS: CIT is effective for ES-SCLC patients regardless of LM status. For patients with LM, PD-1 blockade combined with CT is the best option. For patients without LM, the most beneficial regimen is the combination of anti-angiogenesis, PD-L1 blockade, and CT.

Comparison of human pluripotent stem cell differentiation protocols to generate neuroblastoma tumors.

Neuroblastoma is the most common pediatric extracranial solid tumor and is derived from trunk neural crest cells (tNCC) and its progenitor sympathoadrenal (SA) cells. While human pluripotent stem cell (PSC) models of neuroblastoma have been described, the PSC were differentiated using protocols that made neural crest cells, but not specifically the trunk subtype. Here, we compared four recent protocols to differentiate pluripotent stem cells (PSC) toward SA cells and examined their efficiency at generating SA cells along with earlier cell states (neuromesodermal progenitors [NMP], tNCC), as well as generating MYCN-driven tumors. Interestingly, the protocols that created cells with the highest level of NMP markers did not produce cells with the highest tNCC or SA cell markers. We identified a protocol that consistently produced cells with the highest level of SA markers using two PSC lines of different genders. This protocol also generated tumors with the highest level of PHOX2B, a marker of neuroblastoma. Transcriptionally, however, each protocol generates tumors that resemble neuroblastoma. Two of the protocols repeatedly produced adrenergic neuroblastoma whereas the other two protocols were ambiguous. Thus, we identified a protocol that reliably generates adrenergic neuroblastoma.

Landscape of C-MET overexpression in non-small cell lung cancer: a large-scale study of clinicomolecular features and prognosis based on Chinese data.

Background: Real-world data on C-MET protein overexpression in non-small cell lung cancer (NSCLC) patients, particularly among the Asian Chinese population, are limited. Objectives: This study aimed to evaluate the clinicomolecular characteristics and prognosis of C-MET overexpression in Chinese NSCLC patients, focusing on those with positive C-MET overexpression (immunohistochemistry (IHC) 3+). Design: A retrospective and observational study. Methods: Data were collected from NSCLC patients diagnosed at the First Affiliated Hospital of Guangzhou Medical University between November 2006 and April 2021. We identified C-MET overexpression using IHC and C-MET overexpression positivity was defined as IHC 3+ with ⩾50% tumor cells. Additionally, patient genotypes were collected for subgroup analysis. Results: Data from 9785 NSCLC patients were collected. C-MET (-) accounted for 5% (503/9785), C-MET (+) for 27% (2654/9785), C-MET (++) for 36% (3464/9785), and C-MET (+++) for 32% (3164/9785). Genetic testing was available for 4326 patients. Wild-type was observed in 37% (1591 cases), with epidermal growth factor receptor (EGFR) abnormalities being the most common at 49% (2127 cases). Positive C-MET overexpression correlated significantly with women (p < 0.001), early-stage (p = 0.003), adenocarcinoma (p < 0.001), and driver mutations (p < 0.001). Patients with anaplastic lymphoma kinase (ALK) alterations had a higher occurrence of C-MET overexpression positivity (57.1%). Positive C-MET overexpression was significantly associated with EGFR (p < 0.001), ALK (p < 0.001), and KRAS alterations (p = 0.024). Compared to C-MET overexpression (IHC 0), C-MET overexpression (IHC 2+) (hazard ratio (HR) = 0.455, p < 0.001) and C-MET overexpression (IHC 3+) (HR = 0.569, p < 0.001) were correlated with better overall survival in overall NSCLC patients, especially for C-MET overexpression (IHC 2+). Conclusion: Our study elucidates the clinicomolecular characteristics and prognosis of C-MET overexpression in NSCLC patients, particularly those with positive C-MET overexpression (IHC 3+). This provides insight into the prevalence of C-MET overexpression in Chinese NSCLC patients and offers a basis for considering C-MET overexpression as a prognostic and predictive marker in NSCLC.

Clinical Features of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Induced by Immune Checkpoint Inhibitor versus Non-Immune Checkpoint Inhibitor Drugs in China: A Cross-Sectional Study and Literature Review.

Purpose: Immune checkpoint inhibitors (ICIs) can cause life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Large-scale original research on ICI-induced SJS/TEN is limited. This study aimed to explore the unique clinical characteristics and potential pathophysiological mechanisms of SJS/TEN induced by ICIs. Methods: This cross-sectional study compared the clinical features of SJS/TEN induced by ICIs and non-ICIs, and reviewed the case characteristics of ICI-induced SJS/TEN. Clinical features were analyzed using independent t-tests, Mann-Whitney U-tests, and multivariable regression models. Results: This study enrolled 41 cases of ICI-induced SJS/TEN and 107 non-ICI-induced cases from January 22, 2015, to May 28, 2024. ICI-induced SJS/TEN patients exhibited a trend towards a longer latency period (ß: 17, 95% CI: -1.49 to 35.48), a smaller affected body surface area (BSA) (ß: -40.68, 95% CI: -71.59 to -9.77), and milder oral and ocular mucositis than non-ICI-induced cases. A literature review identified PD-1 inhibitors as the primary ICIs involved and systemic corticosteroids as the most frequent intervention. No statistically significant difference in mortality rate was observed between patients treated with systemic corticosteroids alone and those receiving combination therapies (P= 0.85). The mortality rate for ICI-induced SJS/TEN was 24.5%. Conclusion: This study offered the largest comparative analysis to date, highlighting the unique clinical features of ICI-induced SJS/TEN, including a smaller affected BSA, a prolonged latency period trend, and milder oral and ocular mucositis. We described the epidemiology, clinical presentation, and therapeutic strategies for ICI-induced SJS/TEN. These findings not only contribute to a deeper understanding of the complex immune-inflammatory pathways in severe immune-related cutaneous adverse events (ircAEs) but also may inform the development of more targeted and effective treatments.

A nanoprodrug derived from branched poly (ethylene glycol) recognizes prostate-specific membrane antigen to precisely suppress prostate cancer progression.

Prostate-specific membrane antigen (PSMA) is overexpressed in 80-90 % of prostate cancers (PCa) and is widely used as a diagnostic and therapeutic biomarker. Docetaxel (DTX), an FDA-approved anti-microtubule drug, is commonly employed to manage metastatic castration-resistant PCa; however, DTX therapy is often associated with severe side effects. One promising strategy to mitigate these side effects is the development of nanomedicine by loading small molecules into biocompatible vectors. Poly (ethylene glycol) (PEG) has been extensively used in clinical settings for this purpose, with PEGylated drugs demonstrating significant success. Compared to linear PEG, branched PEG (multi-arm PEG) provides enhanced stability for nanomedicines. In this study, we developed a novel nanoprodrug 4armPEG-Docetaxel DCL (4armPEG-DD) by conjugating a 4-arm PEG with DTX via a reduction-sensitive disulfide bond and further modifying it with 2-[3-[5-amino-1-carboxypentyl]-ureido]-pentanedioic acid (DCL), a PSMA-targeting ligand. Both in vitro and in vivo results demonstrated that the designed nanoprodrug specifically recognized PSMA-positive PCa cells and effectively released DTX in response to the intracellular reducing environment, leading to potent cytotoxic effects on PSMA-positive prostate tumors. Importantly, 4armPEG-DD exhibited improved in vivo safety compared to small-molecule DTX. Thus, we propose that 4armPEG-DD represents a promising candidate for the clinical treatment of PSMA-positive PCa.

Quality problems in clinical practice guidelines and guideline appraisal studies: Should we tolerate or eradicate?

BACKGROUND: Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument have been widely used by scholars around the world to assess the methodological quality of clinical practice guidelines (CPGs). We sought to identify items or domains that are commonly scored low in the assessment, and to systematically review the issues that emerged when evaluators used the AGREE II tool for guideline quality assessment. METHODS: A systematic search was conducted to identify articles published in medically relevant databases from 2022 to 2023 regarding the use of the AGREE II tool for the assessment of CPGs. We extracted six quality domains and overall quality assessment data of CPGs included in the literature, and processed the data using descriptive statistical analysis, difference analysis, regression analysis, and correlation analysis. A seven-point Likert scale was used to assess the reporting quality of the included articles. RESULTS: 151 relevant publications were identified, including 2081 guidelines published between 1990 and 2022. The results of the regression analysis showed a statistically significant impact of all domains on overall guideline quality (p < 0.001; R2 = 0.777). Domain 1, 2, 3, 4, and 6 scores differed significantly over time (p < 0.001) and were increasing. The score was good for Domain 4 (median 78.00 [IQR: 62.75-89.00]; mean 74.34 [SD 18.85]) and Domain 1 (median 78.00 [IQR: 61.00-90.00]; mean 73.57 [SD 21.12]). Scores were generic for Domain 6 (median 58.33 [IQR: 25.00-83.33]; mean 53.98 [SD 34.13]), Domain 2 (median 53.00 [IQR: 33.30-72.10]; mean 53.30 [SD 24.52]) and Domain 3 (median 51.00 [IQR: 26.02-73.00]; mean 50.44 [SD 27.19]). The score was poor for Domain 5 (median 36.20 [IQR: 20.20-58.32]; mean 40.21 [SD 24.90]). In addition, the quality evaluation results of the included articles showed that 33.1% were evaluated as low and 11.9% as very low. CONCLUSIONS: AGREE II tools have facilitated the development of methodological quality for CPGs. Although the quality of CPGs has improved over time, some general low-quality problems still exist, and solving these problems will be an effective way for developers to upgrade the quality of guidelines. In addition, addressing critical issues in the evaluation of guidelines to present high-quality study reports would be another way to guide guideline development.

Inertial coupling of the hummingbird body in the flight mechanics of an escape manoeuvre.

When a hovering hummingbird performs a rapid escape manoeuvre in response to a perceived threat from the front side, its body may go through simultaneous pitch, yaw and roll rotations. In this study, we examined the inertial coupling of the three-axis body rotations and its effect on the flight mechanics of the manoeuvre using analyses of high-speed videos as well as high-fidelity computational modelling of the aerodynamics and inertial forces. We found that while a bird's pitch-up was occurring, inertial coupling between yaw and roll helped slow down and terminate the pitch, thus serving as a passive control mechanism for the manoeuvre. Furthermore, an inertial coupling between pitch-up and roll can help accelerate yaw before the roll-yaw coupling. Different from the aerodynamic mechanisms that aircraft and animal flyers typically rely on for flight control, we hypothesize that inertial coupling is a built-in mechanism in the flight mechanics of hummingbirds that helps them achieve superb aerial agility.

Synergistic Effect of Polyurethane on Pore-Sealing and Lubrication of Microarc Oxidation Coating.

Microarc oxidation (MAO) is a widely used surface treatment technology. However, its processing inevitably leads to the presence of micropores, microcracks, and other defects in the MAO coating. These defects lead to suboptimal tribological performance and diminished corrosion resistance of the MAO coating. Thus, this study proposed a new pore-sealing method with environmental protection and high efficiency. Polyurethane reactive (PUR) composite coating was prepared on the surface of MAO coating. The sealing effect of the PUR sample was analyzed using scanning electron microscopy (SEM). The molecular structure and elemental changes of the coating were analyzed using X-ray photoelectron spectroscopy (XPS). The tribological properties were analyzed using a tribological testing machine, and the corrosion resistance was tested using an electrochemical workstation. The test results show that the lubricity and corrosion resistance of PUR sample are improved significantly compared with MAO coating. When the mass fraction of PUR is 3 wt %, the PUR sample shows the best lubrication performance, and the coefficient of friction decreases by 70.8%. Compared with the traditional sealing technology, this experimental method is simple and low-cost and has a wide application prospect, which promotes the development of MAO technology.

An automated commissioning method based on virtual source models: Customizing Monte Carlo dose verification models for individual accelerators.

BACKGROUND: In pursuit of precise dose calculation and verification, the importance of beam modelling cannot be overstated, as it ensures an accurate distribution of particles incident upon the human body. The virtual source model, as one of the beam modelling methods, offers the advantage of not requiring detailed accelerator information. Although various virtual source models exist, manual adjustment to these models demands a substantial investment of time and computational resources. There has long been a desire to develop an efficient and automated approach for model commissioning. PURPOSE: To develop an automatic commissioning method for the virtual source model to customize the accelerator model for independent Monte Carlo dose verification. METHODS: Initially, the accelerator model is established using the virtual source model and self-developed Jaw and MLC models. Then, a fully automated iteration process is employed to adjust the parameters of the virtual source model. Three types of objective functions are designed to represent differences from water tank measurements. Each objective function is paired with a specific parameter for adjustment, and their effectiveness is demonstrated through physical evidence. In each iteration, parameters with the highest objective function percentage are chosen for adjustment, and step length is determined based on current objective function values. Iteration is terminated when changes in any direction from the optimal solution no longer produce an improvement. Dose verification model for nine accelerators has been accomplished using this method. Additionally, under the same initial conditions, verification models for Versa HD accelerator (FF and FFF modes) are established using this method, Nelder-Mead Simplex optimization method, and the Bayesian optimization method to compare the efficiency and quality of these three iterative approaches. RESULTS: Iterations for all nine accelerators are completed within 30 iterations. The relative dose differences in dose fall-off region compared to water tank measurements are all less than 2%, and the average gamma passing rates (3%/2 mm) for ArcCHECK measurements in QA plans are all higher than 97%. For Versa HD accelerator in FFF and FF modes, the proposed method achieves an average relative dose difference below 1% within 11 and 13 iterations, respectively. In contrast, the Simplex optimization reached 1% within 78 iterations in FFF mode. Furthermore, the Simplex optimization in FF mode and Bayesian optimization in both modes failed to achieve a 1% difference within 100 iterations. CONCLUSIONS: The proposed iterative method achieves fast and automated commissioning of dose verification models, contributing to accurate and reliable clinical dose verification.

The Growth Performance and Nutrient Composition of Black Soldier Fly (Hermetia illucens) Larvae Fed Slaughtered Bovine Blood.

The disposal of slaughterhouse blood poses significant environmental challenges due to its biological instability and high nutrient content. We used a gradient of 10% blood increments (0-100%) to feed BSFL, and the correlation between the proportion of bovine blood and the BSFL weight gain, mortality rate, fatty acid content, and amino acid content was researched. Results indicate a positive correlation between the bovine blood content and BSFL mortality, with survival rates above 95% for blood proportions below 60%. Larval weight exhibited a negative correlation as the bovine blood content increased. Nutritional analysis revealed that the crude protein content in BSFL increased proportionally with bovine blood (14.75-25.45 g/100 g), while the crude fat content decreased correspondingly (10.70-4.66 g/100 g). The sugar content remained relatively constant across groups. Fatty acid analysis showed increased levels of C16:0, C14:0, and C16:1 and decreased levels of C18:1, C18:2, and C18:3 with higher bovine blood contents. The amino acid content generally increased with higher blood proportions. This study highlights the bioconversion potential of BSFL for bovine blood and underscores the impact of protein, lipid, and sugar concentrations in feed on BSFL growth. These findings provide valuable insights for utilizing slaughterhouse waste in BSFL rearing, contributing to the development of more sustainable waste management and animal feed production methods.

Comparative Efficacy and Safety of Ustekinumab and Secukinumab in the Treatment of Generalized Pustular Psoriasis: A 48-Week Retrospective Cohort Study with Genetic Background Analysis.

Purpose: Recent studies have shown that novel biologics may provide significant clinical benefits for patients with generalized pustular psoriasis (GPP). Ustekinumab and secukinumab have been approved in Japan for GPP treatment in adult patients. However, the differences in efficacy and safety of these two drugs in GPP are not known. Aim: Based on the genetic background, we aimed to compare the efficacy and safety of secukinumab and ustekinumab in patients with GPP. Methods: Patients with moderate to severe GPP who were treated with ustekinumab/secukinumab at our department from July 2019 to May 2022 were included in this study and followed up for 48 weeks. The difference in efficacy between ustekinumab and secukinumab was evaluated by assessing changes in body temperature, laboratory indices, recovery of skin lesions, and changes in quality of life. Additionally, we collected patients' saliva for genotyping and explored the effect of CARD14 genetic mutations on clinical efficacy. Results: A total of 65 patients (32 adults and 33 children) with moderate to severe GPP were included in this study. 31 patients received ustekinumab therapy, and 34 patients were treated with secukinumab. Secukinumab demonstrated superiority to ustekinumab, as evidenced by a higher GPPASI 90 response at week 2. Additionally, the efficacy of ustekinumab and secukinumab was found to be independent of the presence of the CARD14 mutation. Conclusion: Secukinumab is superior to ustekinumab in rapidly clearing the skin and improving health-related quality of life. Moreover, the responses to ustekinumab/secukinumab in patients were not influenced by CARD14 gene mutations.

Fund allocation modeling of compensation subjects for various protection levels of the ecological flow in rivers under runoff variations.

Ecological compensation for protecting of river ecological flow (e-flow) is crucial to maintaining the health of river ecosystems; however, determining the fund sharing for ecological compensation can be challenging. To fill this scientific gap, we herein developed a specific framework to determine the fund-sharing of ecological compensation subjects. Such a framework mainly consists of three parts:1) Identifying the subjects who benefit from the consumption and eco-products provided by e-flow protection, and determining the sharing coefficient of the compensation subjects based on the ratio of their economic benefit to the total economic benefit; 2) Evaluating the ecological compensation resulting from the e-flow protection with the help of the production function method; 3) Combining the ecological compensation and compensation sharing coefficient to determine the fund sharing of compensation subjects. We have successfully applied this approach to the Baoji Section of the Weihe River and the Baojixia Yuanshang Irrigation District (BYID). The obtained results revealed that the compensation subjects were Baoji and Xianyang City, and their corresponding fund-sharing coefficients in 2010 in order were 0.71 and 0.29. It was predicted that ecological compensation for e-flow protection would be 209 million yuan in 2010 year, and the corresponding values of capital sharing are 148 million and 61 million yuan. Over the last 23 years (in the time interval of 2000-2022), the share of compensation funds has gradually decreased, indicating an increasing trend with the improvement of the security level. Join us in our mission to protect river ecosystems and maintain a healthy balance by using this approach for ecological compensation.

Palmatine reverse aristolochic acid-induced heart failure through activating EGFR pathway via upregulating IKBKB.

Aristolochic acid (AA) is renowned for engendering nephrotoxicity and teratogenicity. Previous literature has reported that AA treatment resulted in heart failure (HF) via inflammatory pathways. Yet, its implications in HF remain comparatively uncharted territory, particularly with respect to underlying mechanisms. In our study, the zebrafish model was employed to delineate the cardiotoxicity of AA exposure and the restorative capacity of a phytogenic alkaloid palmatine (PAL). PAL restored morphology and blood supply in AA-damaged hearts by o-dianisidine staining, fluorescence imaging, and Hematoxylin and Eosin staining. Furthermore, PAL attenuated the detrimental effects of AA on ATPase activity, implying myocardial energy metabolism recovery. PAL decreased the co-localization of neutrophils with cardiomyocytes, implying an attenuation of the inflammatory response induced by AA. A combination of network pharmacological analysis and qPCR validation shed light on the therapeutic mechanism of PAL against AA-induced heart failure via upregulation of the epidermal growth factor receptor (EGFR) signaling pathway. Subsequent evaluations using a transcriptological testing, inhibitor model, and molecular docking assay corroborated PAL as an IKBKB enzyme activator. The study underscores the possible exploitation of the EGFR pathway as a potential therapeutic target for PAL against AA-induced HF, thus furthering the continued investigation of the toxicology and advancement of protective pharmaceuticals for AA.

Research on Person Re-Identification through Local and Global Attention Mechanisms and Combination Poolings.

This research proposes constructing a network used for person re-identification called MGNACP (Multiple Granularity Network with Attention Mechanisms and Combination Poolings). Based on the MGN (Multiple Granularity Network) that combines global and local features and the characteristics of the MGN branch, the MGNA (Multiple Granularity Network with Attentions) is designed by adding a channel attention mechanism to each global and local branch of the MGN. The MGNA, with attention mechanisms, learns the most identifiable information about global and local features to improve the person re-identification accuracy. Based on the constructed MGNA, a single pooling used in each branch is replaced by combination pooling to form MGNACP. The combination pooling parameters are the proportions of max pooling and average pooling in combination pooling. Through experiments, suitable combination pooling parameters are found, the advantages of max pooling and average pooling are preserved and enhanced, and the disadvantages of both types of pooling are overcome, so that poolings can achieve optimal results in MGNACP and improve the person re-identification accuracy. In experiments on the Market-1501 dataset, MGNACP achieved competitive experimental results; the values of mAP and top-1 are 88.82% and 95.46%. The experimental results demonstrate that MGNACP is a competitive person re-identification network, and that the attention mechanisms and combination poolings can significantly improve the person re-identification accuracy.

Tailoring of Circularly Polarized Beams Employing Bound States in the Continuum in a Designed Photonic Crystal Metasurface Nanostructure.

We propose a photonic crystal (PC) nanostructure that combines bound states In the continuum (BIC) with a high-quality factor up to 107 for emitting circularly polarized beams. We break the in-plane inversion symmetry of the unit cell by tilting the triangular hole of the hexagonal lattice, resulting in the conversion of a symmetrically protected BIC to a quasi-BIC. High-quality circularly polarized light is obtained efficiently by adjusting the tilt angles of the hole and the thickness of the PC layer. By changing the hole's geometry in the unit cell, the Q-factor of circularly polarized light is further improved. The quality factor can be adjusted from 6.0 × 103 to 1.7 × 107 by deliberately changing the shape of the holes. Notably, the proposed nanostructure exhibits a large bandgap, which significantly facilitates the generation of stable single-mode resonance. The proposed structure is anticipated to have practical applications in the field of laser technology, particularly in the advancement of low-threshold PC surface emitting lasers (PCSELs).

Predictive value of changes in basal myocardial 18F-fluorodeoxyglucose uptake for cardiotoxicity in locally advanced esophageal cancer patients receiving definitive radiotherapy.

PURPOSE: To investigate the predictive value of changes in segmental myocardial 18F- fluorodeoxyglucose (FDG) uptake for major adverse cardiac events (MACEs) in patients with locally advanced esophageal cancer undergoing definitive radiation therapy (RT). MATERIALS AND METHODS: Between August 2012 and January 2019, 482 patients with stage II-III esophageal cancer from two institutions were enrolled and divided into the training (n = 285) and external validation (n = 197) cohorts. All patients underwent 18F-FDG PET within 1 week before treatment and within 3 months of treatment. Myocardial delineation was performed using the Carimas software based on the AHA 17-segment model and was automatically divided into basal, middle, and apical regions. The main endpoint was the occurrence of MACEs, including unstable angina, myocardial infarction, coronary revascularization, hospitalization for heart failure or urgent visits, and cardiac death. Analyses included competing risk and Cox regression. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and Brier score. RESULTS: Thirty-four patients (11.9%) developed MACEs at a median follow-up of 78 months. The basal region (median: 19.44 Gy) of the myocardium received the highest radiation dose, followed by the middle (median: 13.02 Gy) and apical regions (median: 9.32 Gy). Multivariate analysis showed that the change ratio in pre- and post-treatment basal myocardial SUVmean (basal ∆SUVRmean) remained significant after adjusting for age, pre-existing cardiac disease, and dosimetric parameters. The AUCs and Brier scores demonstrated favorable predictive accuracies of models integrating variables with significant differences in the multivariate analysis when predicting MACEs in the training and validation cohorts. CONCLUSION: Basal ∆SUVRmean was an independent predictor of MACEs in patients with locally advanced esophageal cancer receiving definitive RT. Changes in basal myocardial FDG uptake are promising biomarkers for predicting radiation-induced cardiotoxicity.

Deteriorating wintertime habitat conditions for waterfowls in Caizi Lake, China: Drivers and adaptive measures.

China has made enormous strides to achieve high-quality development and biodiversity conservation, and the establishment of nature-protected areas is one of the essential initiatives. Caizi Lake involves a natural reserve and two national wetland parks, accommodating winter migratory waterfowl over the middle and lower Yangtze River basin in China. However, the water transfer from the Yangtze River to the Huai River (YR-HR water transfer) has modified the winter hydrological conditions of Caizi Lake, negatively affecting wintertime waterfowl habitats. Hence, conserving wintertime waterfowl habitats necessitates knowledge of the dynamical mechanisms behind the impacts of YR-HR water transfer on wintertime waterfowl habitats and adaptive measures. Here we developed a machine learning model, the normalized difference vegetation index, and on-spot observatory datasets such as the spatial distribution of waterfowl species and underwater topography of Caizi Lake. We found that the rising winter water level of Caizi Lake encroaches on winter waterfowl habitat with extremely high suitability. Meanwhile, rising water levels reduced waterfowl food sources. Thus, rising water levels due to YR-HR water transfer deteriorated waterfowl living conditions over Caizi Lake. Therefore, we proposed adaptive measures to alleviate these negative effects, such as water level regulation, artificial feeding of waterfowls, restoration and reconstruction of contiguous mudflats, grass flats. This study highlights human interferences with waterfowl habitats, necessitating biodiversity conservation at regional scales.

Ultrasound-triggered piezoelectric polyetheretherketone with boosted osteogenesis via regulating Akt/GSK3ß/ß-catenin pathway.

Maxillofacial bone defects can severely impact quality of life by impairing physiological functions such as chewing, breathing, swallowing, and pronunciation. Polyether ether ketone (PEEK) is commonly used for the repair of maxillofacial defects due to its mechanical adaptability, while its osteogenic properties still need refinement. Herein, we have utilized the piezoelectric effect exhibited by barium titanate (BTO) under low-intensity pulsed ultrasound (LIPUS) to develop an ultrasound responsive PEEK (PDA@BTO-SPEEK, PBSP) through the mediating effect of polydopamine (PDA), for repairing maxillofacial bone defects. After modification by PDA@BTO, PBSP possesses better hydrophilicity, which is conducive to cell growth and adhesion. Simultaneously, by virtue of the piezoelectric characteristics of BTO, PBSP obtains a piezoelectric coefficient that matches the bone cortex. Notably, when PBSP is stimulated by LIPUS, it can generate stable electricity and effectively accelerate the osteogenic differentiation of osteoblasts through the regulation of the Piezo1-induced calcium (Ca2+) influx and Akt/GSK3ß/ß-catenin pathway. In addition, PBSP presents satisfactory therapeutic effects in rat skull defect models, and its osteogenic efficiency can be further improved under LIPUS stimulation with high tissue penetration. Collectively, PBSP + LIPUS exhibits great potential as a promising alternative strategy for the repair of maxillofacial bone defects.