Association of CYP7B1 expression with the prognosis of endometrial cancer: a retrospective study.

BACKGROUND: Endometrial cancer (EC) tissues express CYP7B1, but its association with prognosis needs to be investigated. METHODS: Immunohistochemistry and image analysis software were used to assess CYP7B1 protein expression in paraffin-embedded endometrial tumor sections. Associations between CYP7B1 and clinical factors were tested with the Wilcoxon rank-sum test. Kaplan-Meier curves were employed to describe survival, and differences were assessed using the log-rank test. Cox regression analysis was used to assess the association between CYP7B1 expression and the prognosis of patients with EC. RESULTS: A total of 307 patients were enrolled with an average age of 52.6 ± 8.0 years at diagnosis. During the period of follow-up, 46 patients (15.0%) died, and 29 (9.4%) suffered recurrence. The expression of CYP7B1 protein is significantly higher in the cytoplasm than in the nucleus (P < 0.001). Patients aged < 55 years (P = 0.040), ER-positive patients (P = 0.028) and PR-positive patients (P < 0.001) report higher levels of CYP7B1 protein. Both univariate (HR = 0.41, 95% CI: 0.18-0.90, P = 0.025) and multivariate (HR = 0.35, 95%CI:0.16-0.79, P = 0.011) Cox regression analyses demonstrate that high CYP7B1 protein expression predicts longer overall survival (OS). When considering only ER-positive patients (n = 265), CYP7B1 protein expression is more strongly associated with OS (HR = 0.20,95%CI:0.08-0.52, P = 0.001). The 3-year OS and 5-year OS in the low-CYP7B1 subgroup are 81.6% and 76.8%, respectively; while in the high-CYP7B1 subgroup are 93.0% and 92.0%, respectively (P = 0.021). CONCLUSIONS: High CYP7B1 protein expression predicted longer OS, suggesting that it may serve as an important molecular marker for EC prognosis.

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).

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.

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.

Copper ions-photo dual-crosslinked alginate hydrogel for angiogenesis and osteogenesis.

Early healing of bone defects is still a clinical challenge. Many bone-filling materials have been studied, among which photocrosslinked alginate has received significant attention due to its good biocompatibility and morphological plasticity. Although it has been confirmed that photocrosslinked alginate can be used as an extracellular matrix for 3D cell culture, it lacks osteogenesis-related biological functions. This study constructed a copper ions-photo dual-crosslinked alginate hydrogel scaffold by controlling the copper ion concentration. The scaffolds were shaped by photocrosslinking and then endowed with biological functions by copper ions crosslinking. According to in vitro research, the dual-crosslinked hydrogel increased the compressive strength and favored copper dose-dependent osteoblast differentiation and cell surface adherence of rat bone marrow mesenchymal stem cells and the expression of type I collagen (Col1), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), vascular endothelial growth factor (VEGF). In addition, hydrogel scaffolds were implanted into rat skull defects, and more angiogenesis and osteogenesis could be observed in in vivo studies. The above results show that the copper-photo-crosslinked hydrogel scaffold has excellent osseointegration properties and can potentially promote angiogenesis and early healing of bone defects, providing a reference solution for bone tissue engineering materials.

Identifying genetically-supported drug repurposing targets for non-small cell lung cancer through mendelian randomization of the druggable genome.

Background: Lung cancer is responsible for most cancer-related deaths, and non-small cell lung cancer (NSCLC) accounts for the majority of cases. Targeted therapy has made promising advancements in systemic treatment for NSCLC over the last two decades, but inadequate drug targets with clinically proven survival benefits limit its universal application in clinical practice compared to chemotherapy and immunotherapy. There is an urgent need to explore new drug targets to expand the beneficiary group. This study aims to identify druggable genes and to predict the efficacy and prognostic value of the corresponding targeted drugs in NSCLC. Methods: Two-sample mendelian randomization (MR) of druggable genes was performed to predict the efficacy of their corresponding targeted therapy for NSCLC. Subsequent sensitivity analyses were performed to assess potential confounders. Accessible RNA sequencing data were incorporated for subsequent verifications, and Kaplan-Meier survival curves of different gene expressions were used to explore the prognostic value of candidate druggable genes. Results: MR screening encompassing 4,863 expression quantitative trait loci (eQTL) and 1,072 protein quantitative trait loci (pQTL, with 453 proteins overlapping) were performed. Seven candidate druggable genes were identified, including CD33, ENG, ICOSLG and IL18R1 for lung adenocarcinoma, and VSIR, FSTL1 and TIMP2 for lung squamous cell carcinoma. The results were validated by further transcriptomic investigations. Conclusions: Drugs targeting genetically supported genomes are considerably more likely to yield promising efficacy and succeed in clinical trials. We provide compelling genetic evidence to prioritize drug development for NSCLC.

The m6A regulators in prostate cancer: molecular basis and clinical perspective.

Prostate cancer (PCa) is the second leading cause of cancer-related death among men in western countries. Evidence has indicated the significant role of the androgen receptor (AR) as the main driving factor in controlling the development of PCa, making androgen receptor inhibition (ARI) therapy a pivotal management approach. In addition, AR independent signaling pathways also contribute to PCa progression. One such signaling pathway that has garnered our attention is N6-Methyladenosine (m6A) signaling, which refers to a chemical modification on RNA with crucial roles in RNA metabolism and disease progression, including PCa. It is important to comprehensively summarize the role of each individual m6A regulator in PCa development and understand its interaction with AR signaling. This review aims to provide a thorough summary of the involvement of m6A regulators in PCa development, shedding light on their upstream and downstream signaling pathways. This summary sets the stage for a comprehensive review that would benefit the scientific community and clinical practice by enhancing our understanding of the biology of m6A regulators in the context of PCa.

Phloroglucinol-Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome with Subsequent Fulminant Type 1 Diabetes (FT1D): A Rare Case and Literature Review.

This study reported a woman with drug reaction with eosinophilia and systemic symptom (DRESS) syndrome induced by phloroglucinol who developed fulminant type 1 diabetes as sequelae. The literature review emphasized the necessity of at least seven months of follow-up for better management of DRESS syndrome.

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.

Mechanical network motifs as targets for mechanomedicine.

The identification and analysis of network motifs has been widely used in the functional analysis of signaling components, disease discovery and other fields. The positive feedback loop (PFL) is a simple but important network motif. The formation of a PFL is regulated by mechanical cues such as substrate stiffness, fiber stretching and cell compression in the cell microenvironment. Here, we propose a new term, 'mechanical PFL', and analyze the mechanisms of mechanical PFLs at molecular, subcellular and cellular scales. More and more therapies are being targeted against mechanosignaling pathways at the experimental and preclinical stages, and exploring mechanical PFLs as potential mechanomedicine targets could be a new direction for disease treatment.

Exploration of Curvature and Stiffness Dual-Regulated Breast Cancer Cell Motility by a Motor-Clutch Model and Cell Traction Force Characterization.

The migration of breast cancer cells is the main cause of death and significantly regulated by physical factors of the extracellular matrix (ECM). To be specific, the curvature and stiffness of the ECM were discovered to effectively guide cell migration in velocity and direction. However, it is not clear what the extent of effect is when these dual-physical factors regulate cell migration. Moreover, the mechanobiology mechanism of breast cancer cell migration in the molecular level and analysis of cell traction force (CTF) are also important, but there is a lack of systematic investigation. Therefore, we employed a microfluidic platform to construct hydrogel microspheres with an independently adjustable curvature and stiffness as a three-dimensional substrate for breast cancer cell migration. We found that the cell migration velocity was negatively correlated to curvature and positively correlated to stiffness. In addition, curvature was investigated to influence the focal adhesion expression as well as the assignment of F-actin at the molecular level. Further, with the help of a motor-clutch mathematical model and hydrogel microsphere stress sensors, it was concluded that cells perceived physical factors (curvature and stiffness) to cause changes in CTF, which ultimately regulated cell motility. In summary, we employed a theoretical model (motor-clutch) and experimental strategy (stress sensors) to understand the mechanism of curvature and stiffness regulating breast cancer cell motility. These results provide evidence of force driven cancer cell migration by ECM physical factors and explain the mechanism from the perspective of mechanobiology.

Multi-omics analysis unravels chemical roadmap and genetic basis for peach fruit aroma improvement.

Selection of fruits with enhanced health benefits and superior flavor is an important aspect of peach breeding. Understanding the genetic interplay between appearance and flavor chemicals remains a major challenge. We identify the most important volatiles contributing to consumer preferences for peach, thus establishing priorities for improving flavor quality. We quantify volatiles of a peach population consisting of 184 accessions and demonstrate major reductions in the important flavor volatiles linalool and Z-3-hexenyl acetate in red-fleshed accessions. We identify 474 functional gene regulatory networks (GRNs), among which GRN05 plays a crucial role in controlling both red flesh and volatile content through the NAM/ATAF1/2/CUC (NAC) transcription factor PpBL. Overexpressing PpBL results in reduced expression of PpNAC1, a positive regulator for Z-3-hexenyl acetate and linalool synthesis. Additionally, we identify haplotypes for three tandem PpAATs that are significantly correlated with reduced gene expression and ester content. We develop genetic resources for improvement of fruit quality.

RIP3 regulates doxorubicin-induced intestinal mucositis via FUT2-mediated α-1,2-fucosylation.

OBJECTIVE: Intestinal mucositis is one of the common side effects of anti-cancer chemotherapy. However, the molecular mechanisms involved in mucositis development remain incompletely understood. In this study, we investigated the function of receptor-interacting protein kinase 3 (RIP3/RIPK3) in regulating doxorubicin-induced intestinal mucositis and its potential mechanisms. METHODS: Intestinal mucositis animal models were induced in mice for in vivo studies. Rat intestinal cell line IEC-6 was used for in vitro studies. RNA­seq was used to explore the transcriptomic changes in doxorubicin-induced intestinal mucositis. Intact glycopeptide characterization using mass spectrometry was applied to identify α-1,2-fucosylated proteins associated with mucositis. RESULTS: Doxorubicin treatment increased RIP3 expression in the intestine and caused severe intestinal mucositis in the mice, depletion of RIP3 abolished doxorubicin-induced intestinal mucositis. RIP3-mediated doxorubicin-induced mucositis did not depend on mixed lineage kinase domain-like (MLKL) but on α-1,2-fucosyltransferase 2 (FUT2)-catalyzed α-1,2-fucosylation on inflammation-related proteins. Deficiency of MLKL did not affect intestinal mucositis, whereas inhibition of α-1,2-fucosylation by 2-deoxy-D-galactose (2dGal) profoundly attenuated doxorubicin-induced inflammation and mucositis. CONCLUSIONS: RIP3-FUT2 pathway is a central node in doxorubicin-induced intestinal mucositis. Targeting intestinal RIP3 and/or FUT2-mediated α-1,2-fucosylation may provide potential targets for preventing chemotherapy-induced intestinal mucositis.

Sirtuin 5-Mediated Desuccinylation of ALDH2 Alleviates Mitochondrial Oxidative Stress Following Acetaminophen-Induced Acute Liver Injury.

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury. Sirtuins 5 (SIRT5) has been implicated in the development of various liver diseases. However, its involvement in APAP-induced acute liver injury (AILI) remains unclear. The present study aimed to explore the role of SIRT5 in AILI. SIRT5 expression is dramatically downregulated by APAP administration in mouse livers and AML12 hepatocytes. SIRT5 deficiency not only exacerbates liver injury and the inflammatory response, but also worsens mitochondrial oxidative stress. Conversely, the opposite pathological and biochemical changes are observed in mice with SIRT5 overexpression. Mechanistically, quantitative succinylome analysis and site mutation experiments revealed that SIRT5 desuccinylated aldehyde dehydrogenase 2 (ALDH2) at lysine 385 and maintained the enzymatic activity of ALDH2, resulting in the suppression of inflammation and mitochondrial oxidative stress. Furthermore, succinylation of ALDH2 at lysine 385 abolished its protective effect against AILI, and the protective effect of SIRT5 against AILI is dependent on the desuccinylation of ALDH2 at K385. Finally, virtual screening of natural compounds revealed that Puerarin promoted SIRT5 desuccinylase activity and further attenuated AILI. Collectively, the present study showed that the SIRT5-ALDH2 axis plays a critical role in AILI progression and might be a strategy for therapeutic intervention.

Navigating the biophysical landscape: how physical cues steer the journey of bone metastatic tumor cells.

Many tumors prefer to metastasize to bone, but the underlying mechanisms remain elusive. The human skeletal system has unique physical properties, that are distinct from other organs, which play a key role in directing the behavior of tumor cells within bone. Understanding the physical journey of tumor cells within bone is crucial. In this review we discuss bone metastasis in the context of how physical cues in the bone vasculature and bone marrow niche regulate the fate of tumor cells. Our objective is to inspire innovative diagnostic and therapeutic approaches for bone metastasis from a mechanobiological perspective.

Dietary Triple-Strain Bacillus-Based Probiotic Supplementation Improves Performance, Immune Function, Intestinal Morphology, and Microbial Community in Weaned Pigs.

Probiotics provide health benefits and are used as feed supplements as an alternative prophylactic strategy to antibiotics. However, the effects of Bacillus-based probiotics containing more than two strains when supplemented to pigs are rarely elucidated. SOLVENS (SLV) is a triple-strain Bacillus-based probiotic. In this study, we investigate the effects of SLV on performance, immunity, intestinal morphology, and microbial community in piglets. A total of 480 weaned pigs [initial body weight (BW) of 8.13 ± 0.08 kg and 28 days of age] were assigned to three treatments in a randomized complete block design: P0: basal diet (CON); P200: CON + 200 mg SLV per kg feed (6.5 × 108 CFU/kg feed); and P400: CON + 400 mg SLV per kg feed (1.3 × 109 CFU/kg feed). Each treatment had 20 replicated pens with eight pigs (four male/four female) per pen. During the 31 d feeding period (Phase 1 = wean to d 14, Phase 2 = d 15 to 31 after weaning), all pigs were housed in a temperature-controlled nursery room (23 to 25 °C). Feed and water were available ad libitum. The results showed that the pigs in the P400 group increased (p < 0.05) average daily gain (ADG) in phase 2 and tended (p = 0.10) to increase ADG overall. The pigs in the P200 and P400 groups tended (p = 0.10) to show improved feed conversion ratios overall in comparison with control pigs. The pigs in the P200 and P400 groups increased (p < 0.05) serum immunoglobulin A, immunoglobulin G, and haptoglobin on d 14, and serum C-reactive protein on d 31. The pigs in the P200 group showed an increased (p < 0.01) villus height at the jejunum, decreased (p < 0.05) crypt depth at the ileum compared with other treatments, and tended (p = 0.09) to have an increased villus-crypt ratio at the jejunum compared with control pigs. The pigs in the P200 and P400 groups showed increased (p < 0.05) goblet cells in the small intestine. Moreover, the pigs in the P400 group showed down-regulated (p < 0.05) interleukin-4 and tumor necrosis factor-α gene expressions, whereas the pigs in the P400 group showed up-regulated occludin gene expression in the ileum. These findings suggest that SLV alleviates immunological reactions, improves intestinal microbiota balance, and reduces weaning stress in piglets. Therefore, SOLVENS has the potential to improve health and performance for piglets.

Research on Positioning and Navigation System of Greenhouse Mobile Robot Based on Multi-Sensor Fusion.

The labor shortage and rising costs in the greenhouse industry have driven the development of automation, with the core of autonomous operations being positioning and navigation technology. However, precise positioning in complex greenhouse environments and narrow aisles poses challenges to localization technologies. This study proposes a multi-sensor fusion positioning and navigation robot based on ultra-wideband (UWB), an inertial measurement unit (IMU), odometry (ODOM), and a laser rangefinder (RF). The system introduces a confidence optimization algorithm based on weakening non-line-of-sight (NLOS) for UWB positioning, obtaining calibrated UWB positioning results, which are then used as a baseline to correct the positioning errors generated by the IMU and ODOM. The extended Kalman filter (EKF) algorithm is employed to fuse multi-sensor data. To validate the feasibility of the system, experiments were conducted in a Chinese solar greenhouse. The results show that the proposed NLOS confidence optimization algorithm significantly improves UWB positioning accuracy by 60.05%. At a speed of 0.1 m/s, the root mean square error (RMSE) for lateral deviation is 0.038 m and for course deviation is 4.030°. This study provides a new approach for greenhouse positioning and navigation technology, achieving precise positioning and navigation in complex commercial greenhouse environments and narrow aisles, thereby laying a foundation for the intelligent development of greenhouses.