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We explore the interaction between estrogen and PCSK9 and their collective impact on lipid metabolism, especially concerning the regulation of low-density lipoprotein receptor levels. Utilizing both animal and cellular models, including ovariectomized mice and HepG2 cell lines, we demonstrate that estrogen deficiency leads to a disruption in lipid metabolism, characterized by elevated levels of total cholesterol and LDL-C. The study commences with mice undergoing ovariectomy, followed by a diet regimen comprising either high-fat diet or normal feed for a four-week duration. Key assessments include analyzing lipid metabolism, measuring PCSK9 levels in the bloodstream, and evaluating hepatic low-density lipoprotein receptor expression. We will also conduct correlation analyses to understand the relationship between PCSK9 and various lipid profiles. Further, a subset of ovariectomized mice on high-fat diet will undergo treatment with either estrogen or PCSK9 inhibitor for two weeks, with a subsequent re-evaluation of the earlier mentioned parameters. Our findings reveal that estrogen inhibits PCSK9-mediated degradation of low-density lipoprotein receptor, a process crucial for maintaining lipid homeostasis. Through a series of experiments, including immunohistochemistry and western blot analysis, we establish that PCSK9 is involved in lipid metabolism disorders caused by estrogen deficiency and that estrogen regulates PCSK9 and low-density lipoprotein receptor at post-transcriptional level. The study provides a mechanism for the involvement of PCSK9 in elucidating the disorders of lipid metabolism caused by estrogen deficiency due to perimenopause and ovarian decline., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

In recent years, with the rapid advancement of Internet technology and the impact of the COVID-19 pandemic, mobile phones have been used more frequently, the development trend of mobile phone addiction among Chinese college students is a concern to society. This cross-temporal meta-analysis provides compelling evidence of the rising trend of mobile phone addiction in Chinese college students based on data from 42 independent studies (Sample Size = 49,544) over the past decade (2013-2022), and discuss the three important rising periods. Furthermore, extended research has revealed correlated factors of mobile phone addiction among Chinese college students, including gender, anxiety, depression, loneliness, stress, well-being, social support, and resilience. Additionally, the study identified the National internet penetration rate and the National GDP index as significant predictors of mobile phone addiction in Chinese college students. These findings not only reveal the changing trends of mobile phone addiction among Chinese college students, but also enrich the understanding of mobile phone addiction among this population and provide a reference for improving mobile phone addiction among in the future., Competing Interests: 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., (© 2024 The Authors.)

Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including the hypoxia-inducible factor pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5'-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decreased PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5'-phosphate (PLP), and inhibited lysosomal acidification, which in macrophages led to iron dysregulation, TET2 protein loss and delayed resolution of the inflammatory response. Among PLP-dependent metabolism, supersulfide synthesis was suppressed in prolonged hypoxia, resulting in the lysosomal inhibition and consequent proinflammatory phenotypes of macrophages. The PNPO-PLP axis creates a distinct layer of oxygen sensing that gradually shuts down PLP-dependent metabolism in response to prolonged oxygen deprivation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Species richness generally decreases with increasing latitude, a biodiversity gradient that has long been considered as one of the few laws in ecology. This latitudinal diversity gradient has been observed in many major groups of organisms. In plants, the latitudinal diversity gradient has been observed in vascular plants, angiosperms, ferns, and liverworts. However, a conspicuous latitudinal diversity gradient in mosses at a global or continental scale has not been observed until now. Here, we analyze a comprehensive data set including moss species in each band of 20° in latitude worldwide. Our results show that moss species richness decreases strongly with increasing latitude, regardless of whether the globe is considered as a whole or different longitudinal segments (e.g., Old World versus New World) are considered separately. This result holds when variation in area size among latitudinal bands is taken into account. Pearson's correlation coefficient between latitude and species richness is -0.99 for both the Northern and Southern Hemispheres. Because bryophytes are an extant lineage of early land plants and because mosses not only include most of extant species of bryophytes but also are important constituents of most terrestrial ecosystems, understanding geographic patterns of mosses is particularly important. The finding of our study fills a critical knowledge gap., Competing Interests: The authors have no competing interest to declare., (© 2024 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

O-linked-β-D-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation), which is dynamically regulated by O -GlcNAc transferase (OGT) and O -GlcNAcase (OGA), is a post-translational modification involved in multiple cellular processes. O-GlcNAcylation of proteins can regulate their biological functions via crosstalk with other post-translational modifications, such as phosphorylation, ubiquitination, acetylation, and methylation. Liver diseases are a major cause of death worldwide; yet, key pathological features of the disease, such as inflammation, fibrosis, steatosis, and tumorigenesis, are not fully understood. The dysregulation of O-GlcNAcylation has been shown to be involved in some severe hepatic cellular stress, viral hepatitis, liver fibrosis, nonalcoholic fatty acid liver disease (NAFLD), malignant progression, and drug resistance of hepatocellular carcinoma (HCC) through multiple molecular signaling pathways. Here, we summarize the emerging link between O-GlcNAcylation and hepatic pathological processes and provide information about the development of therapeutic strategies for liver diseases.

In recent years, micro/nanoplastics have garnered widespread attention due to their ecological risks. In this study, we investigated the effects of polystyrene nanoparticles (PS-NPs) of different sizes on the growth and biofilm formation of Pseudomonas aeruginosa PAO1. The results demonstrated that exposure to certain concentrations of PS-NPs significantly promoted bacterial biofilm formation. Meanwhile, we comprehensively revealed its mechanism whereby PS-NPs induced oxidative stress and altered bacterial membrane permeability by contacting or penetrating bacterial membranes. To counteract the stimulation by PS-NPs and reduce their toxicity, bacteria enhanced biofilm formation by upregulating the expression of biofilm-related genes, increasing EPS and virulence factors secretion, and enhancing bacterial motility through the participation of the quorum sensing (QS) system. Additionally, we also found that exposure to PS-NPs enhanced bacterial antibiotic resistance, posing a challenge to antimicrobial therapy. Our study reveals the toxic effects of nanoplastics and the defense mechanisms of bacteria, which has important implications for the risk assessment and management of environmental nanoplastics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Obesity, insulin resistance, and hyperandrogenemia are commonly seen in women with polycystic ovary syndrome (PCOS), and these three conditions form a vicious cycle leading to reproductive and metabolic abnormalities. Metformin improves the symptoms of PCOS by increasing insulin sensitivity but is not therapeutically optimal. Recent studies have reported that sodium-glucose co-transporter protein receptor inhibitors improve insulin resistance and reduce the weight of patients with PCOS. We performed a meta-analysis to assess the influence of sodium-glucose co-transporter protein-2 (SGLT2) inhibitors on anthropometric, glycolipid metabolism and reproductive outcomes after therapy of overweight/obese women with PCOS., Methods: We searched the relevant literature published up to April 2023. Information on the effect of SGLT2 inhibitors on overweight/obese patients with PCOS was extracted independently by two reviewers. Review Manager 5.3 was used for meta-analysis., Results: Five randomized controlled trials that met our criteria were retrieved. Our meta-analysis demonstrated that in overweight/obese patients with PCOS, SGLT2 inhibitors treatment was significantly superior to metformin treatment in terms of reducing body weight (P = 0.02, I 2  = 36%), decreasing dehydroepiandrosterone sulfate concentrations [SMD = -0.42, 95% CI (-0.76, -0.07), I 2  = 22%, P = 0.02], and reducing the incidence of nausea [RR = 0.35, 95% CI (0.21, 0.60), I 2  = 71%, P = 0.0001]., Conclusions: SGLT2 inhibitors are a possible alternative therapy for treating overweight/obese women with PCOS who do not respond favorably to metformin treatment. However, further large randomized controlled trials and cost-effectiveness analyses are warranted to guide the implementation of SGLT2 inhibitors treatment in this population., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Vision-language navigation is a task that requires an agent to follow instructions to navigate in environments. It becomes increasingly crucial in the field of embodied AI, with potential applications in autonomous navigation, search and rescue, and human-robot interaction. In this paper, we propose to address a more practical yet challenging counterpart setting - vision-language navigation in continuous environments (VLN-CE). To develop a robust VLN-CE agent, we propose a new navigation framework, ETPNav, which focuses on two critical skills: 1) the capability to abstract environments and generate long-range navigation plans, and 2) the ability of obstacle-avoiding control in continuous environments. ETPNav performs online topological mapping of environments by self-organizing predicted waypoints along a traversed path, without prior environmental experience. It privileges the agent to break down the navigation procedure into high-level planning and low-level control. Concurrently, ETPNav utilizes a transformer-based cross-modal planner to generate navigation plans based on topological maps and instructions. The plan is then performed through an obstacle-avoiding controller that leverages a trial-and-error heuristic to prevent navigation from getting stuck in obstacles. Experimental results demonstrate the effectiveness of the proposed method. ETPNav yields more than 10% and 20% improvements over prior state-of-the-art on R2R-CE and RxR-CE datasets, respectively. Our code is available at https://github.com/MarSaKi/ETPNav.

The fish louse Argulus japonicus , a branchiuran crustacean of the Argulidae family, is attracting increasing attention because of its parasitic tendencies and significant health threats to global fish farming. The mitogenomes can yield a foundation for studying epidemiology, genetic diversity, and molecular ecology and therefore may be used to assist in the surveillance and control of A. japonicus . In this study, we sequenced and assembled the complete mitogenome of A. japonicus to shed light on its genetic and evolutionary blueprint. Our investigation indicated that the 15,045-bp circular genome of A. japonicus encodes 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), and 2 ribosomal RNAs (rRNAs) with significant AT and GC skews. Comparative genomics provided an evolutionary scenario for the genetic diversity of 13 PCGs: all were under purifying selection, with cox1 and nad6 having the lowest and highest evolutionary rates, respectively. Genome-wide phylogenetic trees established a close relationship between species of the families Argulidae (Arguloida) and Armilliferidae (Porocephalida) within Crustacea, and further, A. japonicus and Argulus americanus were determined to be more closely related to each other than to others within the family Argulidae. Single PCG-based phylogenies supported nad1 and nad6 as the best genetic markers for evolutionary and phylogenetic studies for branchiuran crustaceans due to their similar phylogenetic topologies with those of genome-based phylogenetic analyses. To sum up, these comprehensive mitogenomic data of A. japonicus and related species refine valuable marker resources and should contribute to molecular diagnostic methods, epidemiological investigations, and ecological studies of the fish ectoparasites in Crustacea., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Hu, Wang, Zhu, Wei, Fan, Huang, Wang, Wang and Xie.)

In higher education, Personal growth initiative (PGI) has been the focus of attention, personal growth initiative is a fundamental mechanism for individual advancement, equipping college students with the resilience to navigate obstacles and bolstering self-enhancement. The present study comprehensively synthesizes existing research on the factors correlated with personal growth initiative among collegiate populations, aims to identify all correlated factors of college students' personal growth initiative, and the level of correlation. A systematic search was conducted through Scopus, Web of Science, PubMed, JSTOR, PsycINFO, ScienceDirect, and Wiley Online Library, as well as manually search in Google Schalor, spanning to collate research on college students' personal growth initiative. Quantitative synthesis was performed using STATA 17, while sensitivity was tested using a change effect model approach and publication bias was assessed employing Egger's test. After applying the Bonferroni correction, this study found that 18 factors were significantly positively correlated with college students' personal growth initiative, including 4 high-level correlated factors, 10 medium-level correlated factors, and 4 low-level correlated factors, as well as 4 factors were significantly negatively correlated, including 1 medium-level correlated factor and 3 low-level correlated factors. These findings offer valuable insights into personal growth initiative among college students, and the reference for educators and institutional leaders aiming to foster personal growth initiative for college student self-development., Competing Interests: 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., (© 2024 The Authors.)

Rice stem is the sole conduit for cadmium translocation from underground to aboveground. The presence of cadmium can trigger responses of rice stem multi-phenotype, affecting metabolism, reducing yield, and altering composition, which is related to crop growth, food safety, and new energy utilization. Exploring the adversity response of plant phenotypes can provide a reliable assessment of growth status. However, the phytotoxicity and mechanism of cadmium stress on rice stem remain unclear. Here, we systematically revealed the response mechanisms of cadmium accumulation, adversity physiology, and morphological characteristic in rice stem under cadmium stress for the first time with concentration gradients of CK, 5, 25, 50, and 100 μM, and duration gradients of Day 5, Day 10, Day 15, and Day 20. The results indicated that cadmium stress led to a significant increase in cadmium accumulation, accompanied by the adversity response in stem phenotypes. Specifically, cadmium can cause fluctuations in soluble protein and disturbance of malondialdehyde (MDA), which reflects lipid peroxidation induced by cadmium accumulation. Lipid peroxidation inhibited rice growth by causing (1) a reduction in stem length, diameter, and weight, (2) suppression of air cavity, vascular bundle, parenchyma, and epidermal hair, and (3) disruption of cell structure. Furthermore, rapid detection of cadmium was realized based on the combination of laser-induced breakdown spectroscopy (LIBS) and machine learning, which took less than 3 min. The established qualitative model realized the precise discrimination of cadmium stress degrees with a prediction accuracy exceeding 92 %, and the quantitative model achieved the outstanding prediction effect of cadmium, with R p of 0.9944. This work systematically revealed the phytotoxicity of cadmium on rice stem multi-phenotype from a novel perspective of lipid peroxidation and realized the rapid detection of cadmium in rice stem, which provided the technical tool and theoretical foundation for accurate prevention and efficient control of heavy metal risks in crops., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Cyanobacteria are typically of a size that can be observed under a microscope. Here, we present cyanobacteria of a size that can be observed with the naked eye. Arthrospira platensis NCB002 strain showed differentiated morphological characteristics compared to previously reported Arthrospira spp., Methods: Arthrospira platensis NCB002 was obtained by the UV irradiation of Arthrospira sp. NCB001, which was isolated from freshwater and owned by NCell Co., Ltd. A. platensis NIES-39 was obtained from the National Institute for Environmental Studies (Tsukuba, Japan). We used various analytical techniques to determine its overall characteristics., Results and Discussion: The draft genome of strain NCB002 consists of five contigs comprising 6,864,973 bp with a G+C content of 44.3 mol%. The strain NCB002 had an average length of 11.69 ± 1.35 mm and a maximum of 15.15 mm, which is 23.4-50.5 times longer than the length (0.3-0.5 mm) of previously known Arthrospira spp., allowing it to be harvested using a thin sieve. Transcriptome analysis revealed that these morphological differences resulted from changes in cell wall formation mechanisms and increased cell division. Our results show that NCB002 has outstanding industrial value and provides a comprehensive understanding of it., Competing Interests: Authors CL, HN, and ZK were employed by the company NCell 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 © 2024 Lee, Han, Na, Kim, Ahn, Oh and Kim.)

Inflammatory bowel disease (IBD), a chronic inflammatory condition of the human intestine, comprises Crohn's Disease (CD) and Ulcerative Colitis (UC). IBD causes severe gastrointestinal symptoms and increases the risk of developing colorectal carcinoma. Although the etiology of IBD remains ambiguous, complex interactions between genetic predisposition, microbiota, epithelial barrier, and immune factors have been implicated. The disruption of intestinal homeostasis is a cardinal characteristic of IBD. Patients with IBD exhibit intestinal microbiota dysbiosis, impaired epithelial tight junctions, and immune dysregulation; however, the relationship between them is not completely understood. As the largest body surface is exposed to the external environment, the gastrointestinal tract epithelium is continuously subjected to environmental and endogenous stressors that can disrupt cellular homeostasis and survival. Heat shock proteins (HSPs) are endogenous factors that play crucial roles in various physiological processes, such as maintaining intestinal homeostasis and influencing IBD progression. Specifically, HSPs share an intricate association with microbes, intestinal epithelium, and the immune system. In this review, we aim to elucidate the impact of HSPs on IBD development by examining their involvement in the interactions between the intestinal microbiota, epithelial barrier, and immune system. The recent clinical and animal models and cellular research delineating the relationship between HSPs and IBD are summarized. Additionally, new perspectives on IBD treatment approaches have been proposed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The clinical treatment efficacy for implant-associated infections (IAIs), particularly those caused by Methicillin-resistant Staphylococcus aureus (MRSA), remains unsatisfactory, primarily due to the formation of biofilm barriers and the resulting immunosuppressive microenvironment, leading to the chronicity and recurrence of IAIs. To address this challenge, we propose a light-induced immune enhancement strategy, synthesizing BSA@MnO 2 @Ce6@Van (BMCV). The BMCV exhibits precise targeting and adhesion to the S. aureus biofilm-infected region, coupled with its capacity to catalyze oxygen generation from H 2 O 2 in the hypoxic and acidic biofilm microenvironment (BME), promoting oxygen-dependent photodynamic therapy efficacy while ensuring continuous release of manganese ions. Notably, targeted BMCV can penetrate biofilms, producing ROS that degrade extracellular DNA, disrupting the biofilm structure and impairing its barrier function, making it vulnerable to infiltration and elimination by the immune system. Furthermore, light-induced reactive oxygen species (ROS) around the biofilm can lyse S. aureus , triggering bacterium-like immunogenic cell death (ICD), releasing abundant immune costimulatory factors, facilitating the recognition and maturation of antigen-presenting cells (APCs), and activating adaptive immunity. Additionally, manganese ions in the BME act as immunoadjuvants, further amplifying macrophage-mediated innate and adaptive immune responses and reversing the immunologically cold BME to an immunologically hot BME. We prove that our synthesized BMCV elicits a robust adaptive immune response in vivo, effectively clearing primary IAIs and inducing long-term immune memory to prevent recurrence. Our study introduces a potent light-induced immunomodulatory nanoplatform capable of reversing the biofilm-induced immunosuppressive microenvironment and disrupting biofilm-mediated protective barriers, offering a promising immunotherapeutic strategy for addressing challenging S. aureus IAIs.

Aging increases the risks of various diseases and the vulnerability to death. Cellular senescence is a hallmark of aging that contributes greatly to aging and aging-related diseases. This study demonstrates that extracellular vesicles from human urine-derived stem cells (USC-EVs) efficiently inhibit cellular senescence in vitro and in vivo . The intravenous injection of USC-EVs improves cognitive function, increases physical fitness and bone quality, and alleviates aging-related structural changes in different organs of senescence-accelerated mice and natural aging mice. The anti-aging effects of USC-EVs are not obviously affected by the USC donors' ages, genders, or health status. Proteomic analysis reveals that USC-EVs are enriched with plasminogen activator urokinase (PLAU) and tissue inhibitor of metalloproteinases 1 (TIMP1). These two proteins contribute importantly to the anti-senescent effects of USC-EVs associated with the inhibition of matrix metalloproteinases, cyclin-dependent kinase inhibitor 2A (P16 INK4a ), and cyclin-dependent kinase inhibitor 1A (P21 cip1 ). These findings suggest a great potential of autologous USC-EVs as a promising anti-aging agent by transferring PLAU and TIMP1 proteins., (© 2024 The Authors.)

Background: Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis., Methods: Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participants were utilized to evaluate genetically predicted liver fat and volume. Data from the ENIGMA Consortium, comprising 51,665 patients, were used to evaluate the associations between genetic susceptibility, NAFLD risk, liver fat, liver volume, and alterations in cortical thickness (TH) and surface area (SA). Inverse-variance weighted (IVW) estimation, Cochran Q, and MR-Egger were employed to assess heterogeneity and pleiotropy., Results: Overall, NAFLD did not significantly affect cortical SA or TH. However, potential associations were noted under global weighting, relating heightened NAFLD risk to reduced parahippocampal SA and decreased cortical TH in the caudal middle frontal, cuneus, lingual, and parstriangularis regions. Liver fat and volume also influenced the cortical structure of certain regions, although no Bonferroni-adjusted p-values reached significance. Two-step MR analysis revealed that liver fat, AST, and LDL levels mediated the impact of NAFLD on cortical structure. Multivariable MR analysis suggested that the impact of NAFLD on the cortical TH of lingual and parstriangularis was independent of BMI, obesity, hyperlipidemia, and diabetes., Conclusion: This study provides evidence that NAFLD causally influences the cortical structure of the brain, suggesting the existence of a liver-brain axis in the development of NAFLD., (© 2024. The Author(s).)

Purpose: The purpose of this study was to assess the effectiveness of [ 99m Tc]Tc-HYNIC-ALUG SPECT/CT in the initial staging of patients with newly diagnosed PCa., Methods: A retrospective analysis was conducted on 227 consecutive patients who underwent [ 99m Tc]Tc-HYNIC-ALUG SPECT/CT imaging for the primary staging of newly diagnosed PCa. The presence and location of PSMA-positive lesions were determined, and the maximum standardized uptake values (SUVmax) of the primary prostate tumor were also measured. The metastatic findings and SUVmax were stratified according to International Society of Urological Pathology (ISUP) grade, prostate-specific antigen (PSA) levels, and D'Amico classification. Furthermore, the [ 99m Tc]Tc-HYNIC-ALUG SPECT/CT findings were compared to the histopathological findings in patients who had undergone radical prostatectomy with pelvic lymph node dissection (PLND)., Results: Of the 227 patients, 92.1% (209/227) had positive [ 99m Tc]Tc-HYNIC-ALUG SPECT/CT findings. Advanced disease was detected in 38.8% (88/227) of the patients and was positively correlated with increasing ISUP grade and PSA levels. Lymph node metastases (both pelvic and extrapelvic), bone metastases, and visceral metastases were detected in 30.0% (68/227), 25.6% (58/227), and 3.1% (7/227) of the patients, respectively. For the 129 patients who underwent radical prostatectomy with PLND, the sensitivity of [ 99m Tc]Tc-HYNIC-ALUG SPECT/CT in the evaluation of PCa was 90.7% (117/129). The sensitivity, specificity, accuracy, and positive and negative predictive values for detecting pelvic lymph node metastases on [ 99m Tc]Tc-HYNIC-ALUG SPECT/CT were 23.5% (12/51), 93.6% (73/78), 65.9% (85/129), 70.6% (12/17), and 65.2% (73/112), respectively. Among the 209 patients with PSMA-avid primary prostate disease, the SUVmax of the primary prostate tumor was significantly associated with ISUP grade (p<0.0001), PSA levels (p<0.0001), D'Amico classification (p<0.0001), and advanced disease (p<0.0001). Receiver operating characteristic (ROC) analysis revealed that a PSA level >19.8 ng/ml and SUVmax of the primary prostate tumor >7.4 had a sensitivity of 71.6% and 71.6% and specificity of 76.9% and 82.6%, respectively, for detecting metastatic disease., Conclusions: [ 99m Tc]Tc-HYNIC-ALUG SPECT/CT emerges as a valuable imaging tool for the initial staging of newly diagnosed PCa. The presence of advanced disease and the SUVmax of the primary prostate tumor were positively correlated with ISUP grade and PSA levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Ding, Duan, Shi, Tang, Zhang, Zhao, Wu and Gao.)

Background: Scattering photons can seriously contaminate cone-beam CT (CBCT) image quality with severe artifacts and substantial degradation of CT value accuracy, which is a major concern limiting the widespread application of CBCT in the medical field. The scatter kernel deconvolution (SKD) method commonly used in clinic requires a Monte Carlo (MC) simulation to determine numerous quality-related kernel parameters, and it cannot realize intelligent scatter kernel parameter optimization, causing limited accuracy of scatter estimation., Purpose: Aiming at improving the scatter estimation accuracy of the SKD algorithm, an intelligent scatter correction framework integrating the SKD with deep reinforcement learning (DRL) scheme is proposed., Methods: Our method firstly builds a scatter kernel model to iteratively convolve with raw projections, and then the deep Q-network of the DRL scheme is introduced to intelligently interact with the scatter kernel to achieve a projection adaptive parameter optimization. The potential of the proposed framework is demonstrated on CBCT head and pelvis simulation data and experimental CBCT measurement data. Furthermore, we have implemented the U-net based scatter estimation approach for comparison., Results: The simulation study demonstrates that the mean absolute percentage error (MAPE) of the proposed method is less than 9.72% and the peak signal-to-noise ratio (PSNR) is higher than 23.90 dB, while for the conventional SKD algorithm, the minimum MAPE is 17.92% and the maximum PSNR is 19.32 dB. In the measurement study, we adopt a hardware-based beam stop array algorithm to obtain the scatter-free projections as a comparison baseline, and our method can achieve superior performance with MAPE < 17.79% and PSNR > 16.34 dB., Conclusions: In this paper, we propose an intelligent scatter correction framework that integrates the physical scatter kernel model with DRL algorithm, which has the potential to improve the accuracy of the clinical scatter correction method to obtain better CBCT imaging quality., (© 2023 American Association of Physicists in Medicine.)

Osteoarthritis (OA) is a prevalent, chronic degenerative disease that affects people worldwide. It is characterized by the destruction of cartilage and inflammatory reactions. High levels of reactive oxygen species (ROS) cause oxidative stress, which damages lipids, proteins, and DNA, leading to cell damage and death. Furthermore, ROS also induces the production of inflammatory cytokines and cell chemotaxis, further worsening the inflammatory response and damaging cartilage resulted in limited movement. Herein, this work reports a dual-functional injectable hydrogel, which can help inhibit inflammation by scavenging ROS and provide lubrication to reduce wear and tear on the joints. To create the hydrogel, 3-aminophenylboronic acid modified hyaluronic acid is synthesized, then which is crosslinked with hydroxyl-containing polyvinyl alcohol (PVA) to construct a dual dynamic covalent crosslinked hydrogel oHA-PBA-PVA gel, Gel (HPP). The hydrogel mentioned here possesses a unique bond structure that allows it to be injected, self-heal, and provide lubrication. This innovative approach offers a new possibility for treating osteoarthritis by combining anti-inflammatory and lubrication effects., (© 2023 Wiley-VCH GmbH.)

Geometric deep learning has been revolutionizing the molecular modeling field. Despite the state-of-the-art neural network models are approaching ab initio accuracy for molecular property prediction, their applications, such as drug discovery and molecular dynamics (MD) simulation, have been hindered by insufficient utilization of geometric information and high computational costs. Here we propose an equivariant geometry-enhanced graph neural network called ViSNet, which elegantly extracts geometric features and efficiently models molecular structures with low computational costs. Our proposed ViSNet outperforms state-of-the-art approaches on multiple MD benchmarks, including MD17, revised MD17 and MD22, and achieves excellent chemical property prediction on QM9 and Molecule3D datasets. Furthermore, through a series of simulations and case studies, ViSNet can efficiently explore the conformational space and provide reasonable interpretability to map geometric representations to molecular structures., (© 2024. The Author(s).)

Purpose: Intensity-modulated radiotherapy (IMRT) is currently the most important treatment method for nasopharyngeal carcinoma (NPC). This study aimed to enhance prediction accuracy by incorporating dose information into a deep convolutional neural network (CNN) using a multichannel input method. Methods: A target conformal plan (TCP) was created based on the maximum planning target volume (PTV). Input data included TCP dose distribution, images, target structures, and organ-at-risk (OAR) information. The role of target conformal plan dose (TCPD) was assessed by comparing the TCPD-CNN (with dose information) and NonTCPD-CNN models (without dose information) using statistical analyses with the ranked Wilcoxon test ( P  < .05 considered significant). Results: The TCPD-CNN model showed no statistical differences in predicted target indices, except for PTV60, where differences in the D98% indicator were < 0.5%. For OARs, there were no significant differences in predicted results, except for some small-volume or closely located OARs. On comparing TCPD-CNN and NonTCPD-CNN models, TCPD-CNN's dose-volume histograms closely resembled clinical plans with higher similarity index. Mean dose differences for target structures (predicted TCPD-CNN and NonTCPD-CNN results) were within 3% of the maximum prescription dose for both models. TCPD-CNN and NonTCPD-CNN outcomes were 67.9% and 54.2%, respectively. 3D gamma pass rates of the target structures and the entire body were higher in TCPD-CNN than in the NonTCPD-CNN models ( P  < .05). Additional evaluation on previously unseen volumetric modulated arc therapy plans revealed that average 3D gamma pass rates of the target structures were larger than 90%. Conclusions: This study presents a novel framework for dose distribution prediction using deep learning and multichannel input, specifically incorporating TCPD information, enhancing prediction accuracy for IMRT in NPC treatment., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: It was previously found that 3'-Daidzein Sulfonate Sodium (DSS) exhibits protective effects on cerebral ischemia/reperfusion injury (CI/RI)., Aim: This study aimed to explore the underlying molecular mechanisms involved in the neuroprotective effects of DSS against ischemic stroke., Methods: In this study, rats with transient middle cerebral artery occlusion (tMCAO) were used as an in vivo model, whereas PC12 cells treated with glutamate alone and rat primary cortical neurons treated with the combination of glutamate and glycine were used as in vitro models. Cell viability and lactate dehydrogenase (LDH) release were used to evaluate cell injury. Cell apoptosis was determined by flow cytometry. Quantitative polymerase chain reaction (qPCR), Western blotting, and immunofluorescent staining methods were used to determine the mRNA expressions and protein levels and location., Results: It was found that DSS significantly suppressed the impaired viability of PC12 cells induced by glutamate. DSS also increased cell viability while reducing the LDH release and apoptosis in primary cortical neurons injured by glutamate and glycine. In addition, DSS decreased GluN2B subunit expression while enhancing the expressions of GluN2A subunit and PSD95 in tMCAO rats' brains., Conclusion: This study demonstrated that DSS protects against excitotoxic damage in neurons induced by CI/RI through regulating the expression of NMDA receptors and PSD95. Our findings provide experimental evidence for the potential clinical administration of DSS in ischemic stroke., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5 + BMSCs and Tek + BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5 + TEK + ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5 + BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition., (© 2023. The Author(s).)

We investigated the geographical and environmental distance-decay relationships for both of the two bacteria in the Haihe River, Tianjin, China. HNA bacteria exhibited a stronger geographical variation-dependent pattern while LNA bacteria exhibited a stronger environmental variation-dependent pattern. Variance partition analysis (VPA), Mantel test, and partial mantel test validated the discrepant impacts of geographical distance and environmental factors on their two communities. The heterogeneous selection dominated community assembly of LNA bacteria demonstrates their greater sensitivity to environmental conditions. As the deterministic environmental factor, anthropogenic original dissolved organic matter (DOM) functions exclusively on LNA bacteria, and it is the critical factor leading to the discrepant biogeographical patterns of LNA and HNA bacteria. LNA bacteria interact with HNA bacteria and mediate the DOM driving total bacteria assembly. The LNA keystone taxa, Pseudomonas, Rheinheimera, Candidatus Aquiluna, and hgcl clade are capable to compete with HNA bacteria for anthropogenic original DOM, and are potential indicators of anthropogenic pollution. Our research reveals the non-negligible effect of the LNA bacteria in regulating the ecological response of total bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Nanoparticles (NPs) hold a great promise in combating rheumatoid arthritis, but are often compromised by their toxicities because the currently used NPs are usually synthesized by chemical methods. Our group has previously fabricated Ångstrom-scale silver particles (AgÅPs) and demonstrated the anti-tumor and anti-sepsis efficacy of fructose-coated AgÅPs (F-AgÅPs). This study aimed to uncover the efficacy and mechanisms of F-AgÅPs for arthritis therapy., Methods: We evaluated the efficacy of F-AgÅPs in collagen-induced arthritis (CIA) mice. We also compared the capacities of F-AgÅPs, the commercial AgNPs, and the clinical drug methotrexate (MTX) in protecting against K/BxN serum-transfer arthritis (STA) mice. Moreover, we evaluated the effects of F-AgÅPs and AgNPs on inflammation, osteoclast formation, synoviocytes migration, and matrix metalloproteinases (MMPs) production in vitro and in vivo. Meanwhile, the toxicities of F-AgÅPs and AgNPs in vitro and in vivo were also tested., Results: F-AgÅPs significantly prevented bone erosion, synovitis, and cartilage damage, attenuated rheumatic pain, and improved the impaired motor function in mouse models of CIA or STA, the anti-rheumatic effects of which were comparable or stronger than AgNPs and MTX. Further studies revealed that F-AgÅPs exhibited similar or greater inhibitory abilities than AgNPs to suppress inflammation, osteoclast formation, synoviocytes migration, and MMPs production. No obvious toxicities were observed in vitro and in vivo after F-AgÅPs treatment., Conclusions: F-AgÅPs can effectively alleviate arthritis without notable toxicities and their anti-arthritic effects are associated with the inhibition of inflammation, osteoclastogenesis, synoviocytes migration, and MMPs production. Our study suggests the prospect of F-AgÅPs as an efficient and low-toxicity agent for arthritis therapy., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The expansion effects of several new microimplant-assisted rapid palatal expanders (MARPEs) manufactured by 3-dimensional printing technology were evaluated by finite element analysis (FEA). The aim was to identify a novel MARPE suitable for treating maxillary transverse deficiency., Methods: The finite element model was established using MIMICS software (version 19.0; Materialise, Leuven, Belgium). First, the appropriate microimplant insertion characteristics were identified via FEA, and several MARPEs with the above insertion patterns were manufactured by 3-dimensional printing technology. Then, the stress distribution and displacement prediction of the 4 MARPEs and hyrax expander (model E) were evaluated via FEA: bone-borne (model A), bone-tooth-borne (model B), bone-mucous-borne (model C), bone-tooth-mucous-borne (model D)., Results: Monocortical microimplants perpendicular to the cortical bone on the coronal plane resulted in better expansion effects. Compared with a conventional hyrax expander, the orthopedic expansion of each of the 4 MARPEs was far larger, the parallelism was greater, and the posterior teeth tipping rate was lower. Among them, the expansion effects of models C and D were the best; the von Mises peak values on the surfaces of the microimplants were smaller than those of models A and B., Conclusions: This study may demonstrate that the 4 MARPEs obtained more advantageous orthopedic expansion effects than a hyrax expander. Models C and D obtained better biomechanical effects and had better primary stability. Overall, model D is the recommended expander for treating maxillary transverse deficiency because its structure acts like an implant guide and is beneficial for the accurate insertion of the microimplant., (Copyright © 2023 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Background: Osteomyelitis causes marked disability and is one of the most challenging diseases for orthopaedists to treat because of the considerable rate of infection recurrence. In this study, we proposed and assessed the debridement-reconstruction-docking (DRD) system for the treatment of lower-extremity osteomyelitis. This procedure comprises 3 surgical stages and 2 preoperative assessments; namely, pre-debridement assessment, debridement, pre-reconstruction assessment, reconstruction, and docking-site management. We evaluated the use of the DRD system compared with the Ilizarov technique, which is defined as a 1-stage debridement, osteotomy, and bone transport., Methods: This retrospective cohort included 289 patients who underwent either DRD or the Ilizarov technique for the treatment of lower-extremity osteomyelitis at a single institution between January 2013 and February 2021 and who met the eligibility criteria. The primary outcome was the rate of infection recurrence. Secondary outcomes included the external fixator index (EFI), refracture rate, and the Paley classification for osseous and functional results. An inverse-probability-weighted regression adjustment model was utilized to estimate the effect of the DRD system and Ilizarov technique on the treatment of lower-extremity osteomyelitis., Results: A total of 131 and 158 patients underwent DRD or the Ilizarov technique, respectively. The inverse-probability-weighted regression adjustment model suggested that DRD was associated with a significant reduction in infection recurrence (risk ratio [RR], 0.26; 95% confidence interval [CI], 0.13 to 0.50; p < 0.001) and EFI (-6.9 days/cm, 95% CI; -8.3 to -5.5; p < 0.001). Patients in the DRD group had better Paley functional results than those in the Ilizarov group (ridit score, 0.55 versus 0.45; p < 0.001). There was no significant difference between the 2 groups in the rate of refracture (RR, 0.87; 95% CI, 0.42 to 1.79; p = 0.71) and Paley osseous results (ridit score, 0.51 versus 0.49; p = 0.39)., Conclusions: In this balanced retrospective cohort of patients with lower-extremity osteomyelitis, the use of the DRD system was associated with a reduced rate of infection recurrence, a lower EFI, and better Paley functional results compared with the use of the Ilizarov technique., Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H647 )., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

BRAF is frequently mutated in various cancer types and contributes to tumorigenesis and metastasis. As an important switch in RAS signaling pathway, BRAF typically enables the activation of MEK and ERK, and its mutation significantly promotes metastasis. However, whether BRAF could stimulate metastasis via a distinct manner is still unknown. Herein, we found that a portion of the BRAF protein localized at the plasma membrane and that the BRAF V600E mutation led to abundant formation of filopodia, which is a hallmark of invasive cancer cells. Mechanistically, BRAF physically interacts with the pseudopod formation-related protein Vasodilator-stimulated phosphoprotein (VASP), and BRAF specifically catalyzes VASP phosphorylation at Ser157. VASP depletion or disruption of Ser157 phosphorylation preferentially reduced the motility, invasion and metastasis of tumor cells harboring oncogenic BRAF or KRAS. Moreover, in clinical cancer tissues, BRAF V600E was positively correlated with the extent of invasion, and tissues with BRAF V600E expression exhibited elevated levels of VASP Ser157 phosphorylation. Our study therefor reveals a noncanonical mechanism by which oncogenic BRAF or KRAS promotes metastasis, suggests that VASP Ser157 phosphorylation might serve as a valuable therapeutic target in BRAF or KRAS mutant cancers., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Joint stiffness results from the coupling of the nervous system and joint mechanics, and thus stiffness is a comprehensive representation of joint stability. It has been reported that moxibustion can alleviate general weakness and fatigue symptoms and subsequently may influence joint stiffness. This study investigated whether moxibustion could enhance knee joint stiffness in recreational athletes pre- and post-fatigue., Methods: Eighteen participants were randomized into intervention (5 males: 20.6 ± 1.5 yr; 4 females: 20.8 ± 1.5 yr) and control groups (5 males: 19.4 ± 0.9 yr; 4 females: 20.5 ± 0.6 yr). The intervention group received indirect moxibustion applied to acupoints ST36 (bilateral) and CV4 for 30 min every other day for 4 consecutive weeks. The control group maintained regular exercise without moxibustion. Peak torque (PT) of right knee extensor, relaxed and contracted muscle stiffness (MS) of vastus lateralis, and knee extensor musculoarticular stiffness (MAS) was assessed with an isokinetic dynamometer (IsoMed 2000), myometer, and free oscillation technique, respectively. Measurements were taken at three time points: pre-intervention, post-intervention/pre-fatigue, and post-fatigue., Results: MAS (P = 0.006) and PT (P = 0.007) in the intervention group increased more from pre-to post-intervention compared with the control group. Post-fatigue MAS (P = 0.016) and PT (P = 0.031) increased more in the intervention group than in the control group., Conclusion: Moxibustion enhanced PT and knee MAS, suggesting that this intervention could be used in injury prevention and benefit fatigue resistance in young recreational athletes., Competing Interests: The authors declare that they have no competing interests., (© 2023 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

Background: The objective of this study was to investigate the correlation between the 7-joint ultrasound score (US7) and disease activity in patients with rheumatoid arthritis (RA)., Methods: Forty-four patients with active RA were assessed, and the correlation between US7 and disease activity indicators such as the disease activity score (DAS28), rheumatoid factor (RF), the erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was analyzed. In addition, the proportions of US7 points accounted for by different joint regions and joint surfaces were analyzed., Results: RF, CRP, and ESR were significantly increased in the RA group compared with the control group ( P < 0.05). In the RA group, DAS28 ( r = 0.0.561, P < 0.01), RF ( r = 0.635, P < 0.01), ESR ( r = 0.585, P < 0.01), and CRP ( r = 0.492, P < 0.01) were positively correlated with US7. In terms of contributions to US7, the most susceptible joint surface is the dorsal surface, and the most susceptible joint area is the dorsal wrist., Conclusion: US7 is positively correlated with disease activity indicators of RA, which can objectively reflect disease activity in RA patients and provide a reference for clinical diagnosis and efficacy evaluation., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Medical Ultrasound.)

The petrochemical industry is an integral contributor to the global economy and plays a critical role in improving the lives of people worldwide. However, its development has also led to frequent accidents, and the evolution and global impact of these risks have not been adequately assessed. This study is aimed at quantitatively analyzing the current state of petrochemical risk and its impact on industrial development in 58 coastal countries (regions) worldwide by identifying petrochemical risk impact indicators and constructing threshold regression models. We showed that the global petrochemical risk has been unevenly decreasing in recent years. In some countries (regions), the petrochemical risk remains unchanged or is increasing; in particular, coastal provinces of China need to address this issue. Moreover, when industrialization and economic development levels are < 53.6 and 34,918.4 USD/person, respectively, petrochemical accidents negatively affect industrial development; however, above these thresholds, they do not impact industrial development. Coastal areas of China and some developing countries are far below these thresholds. Therefore, the risk from petrochemicals remains a critical factor affecting industrial development in countries with low industrialization levels., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The excessive inflammatory response of macrophages plays a vital role in the pathogenesis of various diseases. The dynamic metabolic alterations in macrophages, including amino acid metabolism, are known to orchestrate their inflammatory phenotype. To explore a new metabolic pathway that regulates the inflammatory response, we examined metabolome changes in mouse peritoneal macrophages (PMs) in response to lipopolysaccharide (LPS) and found a coordinated increase of cysteine and its related metabolites, suggesting an enhanced demand for cysteine during the inflammatory response. Because Slc7a11, which encodes a cystine transporter xCT, was remarkably upregulated upon the pro-inflammatory challenge and found to serve as a major channel of cysteine supply, we examined the inflammatory behavior of Slc7a11 knockout PMs (xCT-KO PMs) to clarify an impact of the increased cysteine demand on inflammation. The xCT-KO PMs exhibited a prolonged upregulation of pro-inflammatory genes, which was recapitulated by cystine depletion in the culture media of wild-type PMs, suggesting that cysteine facilitates the resolution of inflammation. Detailed analysis of the sulfur metabolome revealed that supersulfides, such as cysteine persulfide, were increased in PMs in response to LPS, which was abolished in xCT-KO PMs. Supplementation of N-acetylcysteine tetrasulfide (NAC-S2), a supersulfide donor, attenuated the pro-inflammatory gene expression in xCT-KO PMs. Thus, activated macrophages increase cystine uptake via xCT and produce supersulfides, creating a negative feedback loop to limit excessive inflammation. Our study highlights the finely tuned regulation of macrophage inflammatory response by sulfur metabolism., Competing Interests: Declaration of competing interest The authors declare no competing financial or nonfinancial interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Machine learning force fields (MLFFs) have gained popularity in recent years as they provide a cost-effective alternative to ab initio molecular dynamics (MD) simulations. Despite a small error on the test set, MLFFs inherently suffer from generalization and robustness issues during MD simulations. To alleviate these issues, we propose global force metrics and fine-grained metrics from element and conformation aspects to systematically measure MLFFs for every atom and every conformation of molecules. We selected three state-of-the-art MLFFs (ET, NequIP, and ViSNet) and comprehensively evaluated on aspirin, Ac-Ala3-NHMe, and Chignolin MD datasets with the number of atoms ranging from 21 to 166. Driven by the trained MLFFs on these molecules, we performed MD simulations from different initial conformations, analyzed the relationship between the force metrics and the stability of simulation trajectories, and investigated the reason for collapsed simulations. Finally, the performance of MLFFs and the stability of MD simulations can be further improved guided by the proposed force metrics for model training, specifically training MLFF models with these force metrics as loss functions, fine-tuning by reweighting samples in the original dataset, and continued training by recruiting additional unexplored data., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

The purpose of the current study was to develop spatially and velocity-selective (SVS) magnetization preparation pulses for noncontrast-enhanced peripheral MR angiography (MRA) to provide comparisons with velocity-selective (VS) MRA with comparison to velocity-selective (VS). VS preparation pulses were designed by concatenating multiple excitation steps, each of which was a combination of a hard RF pulse, VS unipolar gradient pulses, and refocusing RF pulses. SVS preparation pulses were designed by replacing the hard RF pulse with a sinc-shaped RF pulse combined with a symmetric tripolar gradient pulse (which does not perturb the velocity encoding by the VS unipolar gradient pulses). Numerical simulations were performed to verify the intended hybrid excitation selectivity of SVS pulses taking account of tissue relaxation, magnetic field errors, and eddy currents. In vivo experiments were performed in healthy subjects to verify the hybrid excitation selectivity, as well as to demonstrate the visualization of the entire peripheral arteries using six-station protocols. As demonstrated by numerical simulations, SVS preparation yielded a notch-shaped longitudinal magnetization (M z )-velocity response within the spatial stopband (the same as VS preparation) and preserved the M z of spins outside the stopband, regardless of its velocity. We confirmed these observations also through in vivo tests with good agreement in normalized arterial and muscle signal intensities. In six-station peripheral MRA experiments, the proposed SVS-MRA yielded significantly higher arterial signal-to-noise ratio (SNR) (51.6 ± 14.3 vs. 38.9 ± 10.9; p < 0.001) and contrast-to-noise ratio (CNR) (41.2 ± 13.0 vs. 31.3 ± 10.5; p < 0.001) compared with VS-MRA. The proposed SVS-MRA improves arterial SNR and CNR compared with VS-MRA by mitigating undesired presaturation of arterial blood upstream the imaging field of view., (© 2023 John Wiley & Sons Ltd.)

A solid skin layer inevitably forms on the foam surface for supercritical carbon dioxide (sc-CO 2 ) foaming technology, leading to deterioration of some inherent properties of polymeric foams. In this work, skinless polyphenylene sulfide (PPS) foam was fabricated with a surface-constrained sc-CO 2 foaming method by innovatively constructing aligned epoxy resin/ferromagnetic graphene oxide composites (EP/GO@Fe 3 O 4 ) as a CO 2 barrier layer under a magnetic field. Introduction of GO@Fe 3 O 4 and its ordered alignment led to an obvious decrease in the CO 2 permeability coefficient of the barrier layer, a significant increase of the CO 2 concentration in the PPS matrix, and a decrease of desorption diffusivity in the depressurization stage, suggesting that the composite layers effectively inhibited the escape of CO 2 dissolved in the matrix. Meanwhile, the strong interfacial interaction between the composite layer and the PPS matrix remarkably enhanced the heterogeneous nucleation of cells at the interface, resulting in elimination of the solid skin layer and formation of an obvious cellular structure on the foam surface. Moreover, by the alignment of GO@Fe 3 O 4 in EP, the CO 2 permeability coefficient of the barrier layer became much lower, and the cell density on the foam surface further increased with decreasing cell size, which was even higher than that of the cross section of foam, attributed to stronger heterogeneous nucleation at the interface than the homogeneous nucleation in the core region of the sample. As a result, the thermal conductivity of the skinless PPS foam reached as low as 0.0365 W/m·k, decreasing by 49.5% compared with that of regular PPS foam, showing a remarkable improvement in the thermal insulation properties of PPS foam. This work provided a novel and effective method for fabricating skinless PPS foam with enhanced thermal insulation properties.

Patients with hepatic fibrosis (HF) have a high risk of developing liver cirrhosis and hepatocellular carcinoma, and there is an urgent need for preventive strategies to block this process. Previous studies have found that disordered inflammation and oxidative damage play important roles in HF progression, suggesting two attractive therapeutic targets. Herein, a new kind of bioinspired microcapsules with a core-shell structure is generated using microfluidics. Polydopamine nanoparticles (PDANPs), a synthetic analogue of natural melanin, are embedded in the polymer shell to provide antioxidative properties for these microcapsules. The aqueous core is used to encapsulate ketone body β-hydroxybutyrate (BHB), an energy metabolite recently known to have regulating effects of cellular signals involved in chronic inflammation. In a HF mouse model, the BHB-encapsulated PDANPs-embedded microcapsules (BHB-PDA-MCs) can not only decrease the severity of inflammatory response, but also the level of oxidative stress. As a result, this combinational strategy is demonstrated to prevent the activation of hepatic stellate cells, the accumulation of extracellular matrix, and the damage of hepatic lobules. These findings indicate that BHB-PDA-MCs can be a promising drug delivery system and have a synergistic effect on HF management., Competing Interests: 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., (© 2023 The Authors.)

Traditional wound dressings have poor mechanical properties and a single function, which cannot achieve rapid healing of diabetic wounds in a unique physiological microenvironment. In order to develop multifunctional hydrogel dressings with appropriate biological activity to accelerate wound healing and obtain better clinical therapeutic effects, herein we report a hybrid system based on drug loaded mesoporous silica and injectable polymer hydrogels mixed with hypoglycemic drug metformin (Met) as a dressing for diabetic wounds. Firstly, a copolymer with the phenylboronic acid group in the side group, poly(acrylamide- co -dimethylaminopropylacrylamide- co -methacrylamidophenylboronic acid) (abbreviated as PB), was prepared. PB was mixed with polyvinyl alcohol (PVA) to obtain an injectable hydrogel (named PP) with pH/glucose dual responsiveness, which was formed through the combination of the phenylborate group of PB and o -diol of PVA. In another reaction, polydopamine-modified mesoporous silica nanoparticles (MSN@PDA) were prepared and used to adsorb antibiotic tetracycline hydrochloride (TH) to obtain drug-loaded MSN@PDA-TH nanoparticles. Subsequently, the hybrid hydrogel dressing (abbreviated as PP/MSN@PDA-TH/Met) was obtained by mixing PB, PVA, Met and MSN@PDA-TH. The self-healing, rheological and adhesive properties of the hybrid hydrogel were characterized. The results show that the hydrogel dressing has good physical properties. Met and TH were released in vitro in different pH media and glucose environments. The results show that the hydrogel dressing has dual responsiveness towards pH and glucose, and can continuously release metformin and tetracycline, which is conducive to accelerating wound healing. The antimicrobial activity, ROS clearance ability and biocompatibility of the hydrogel dressing were evaluated. The results indicate that the hydrogel dressing was multifunctional. Finally, a full-thickness wound repair model of diabetic mice induced by streptozotocin (STZ) was established. The hybrid hydrogel dressing was applied to the wound surface of mice. The wound healing testing on diabetic mice confirmed that the wound covered with the hybrid hydrogel dressing was completely healed with the formation of the new skin and hair within 9 days to 12 days. Histological analysis indicates that, compared to the PBS control, the hydrogel dressing did not cause significant inflammation in the wound, and a large number of blood vessels, glands and hair follicles appeared. This study provides a good strategy for multi-drug synergistic treatment of diabetic foot ulcers.

Background: The energy spectrum is the property of the X-ray tube that describes the energy fluence per unit interval of photon energy. The existing indirect methods for estimating the spectrum ignore the influence caused by the voltage fluctuation of the X-ray tube., Methods: In this work, we propose a method for estimating the X-ray energy spectrum more accurately by including the voltage fluctuation of the X-ray tube. It expresses the spectrum as the weighted summation of a set of model spectra within a certain voltage fluctuation range. The difference between the raw projection and the estimated projection is considered as the objective function for obtaining the corresponding weight of each model spectrum. The equilibrium optimizer (EO) algorithm is used to find the weight combination that minimizes the objective function. Finally, the estimated spectrum is obtained. We refer to the proposed method as the poly-voltage method. The method is mainly aimed at the cone-beam computed tomography (CBCT) system., Results: The model spectra mixture evaluation and projection evaluation showed that the reference spectrum can be combined by multiple model spectra. They also showed that it is appropriate to choose about 10% of the preset voltage as the voltage range of the model spectra, which can match the reference spectrum and projection quite well. The phantom evaluation showed that the beam-hardening artifact can be corrected using the estimated spectrum via the poly-voltage method, and the poly-voltage method provides not only the accurate reprojection but also an accurate spectrum. The normalized root mean square error (NRMSE) index between the spectrum generated via the poly-voltage method and the reference spectrum could be kept within 3% according to above evaluations. There existed a 1.77% percentage error between the estimated scatter of polymethyl methacrylate (PMMA) phantom using the two spectra generated via the poly-voltage method and the single-voltage method, and it could be considered for scatter simulation., Conclusions: Our proposed poly-voltage method could estimate the spectrum more accurately for both ideal and more realistic voltage spectra, and it is robust to the different modes of voltage pulse., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1055/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Magnetic materials in tissue, such as iron, calcium, or collagen, can be studied using quantitative susceptibility mapping (QSM). To date, QSM has been overwhelmingly applied in the brain, but is increasingly utilized outside the brain. QSM relies on the effect of tissue magnetic susceptibility sources on the MR signal phase obtained with gradient echo sequence. However, in the body, the chemical shift of fat present within the region of interest contributes to the MR signal phase as well. Therefore, correcting for the chemical shift effect by means of water-fat separation is essential for body QSM. By employing techniques to compensate for cardiac and respiratory motion artifacts, body QSM has been applied to study liver iron and fibrosis, heart chamber blood and placenta oxygenation, myocardial hemorrhage, atherosclerotic plaque, cartilage, bone, prostate, breast calcification, and kidney stone., (© 2023 International Society for Magnetic Resonance in Medicine.)

The root is an important organ affecting cadmium accumulation in grains, but there is no comprehensive research involving rice root phenotype under cadmium stress yet. To assess the effect of cadmium on root phenotypes, this paper investigated the response mechanism of phenotypic information including cadmium accumulation, adversity physiology, morphological parameters, and microstructure characteristics, and explored rapid detection methods of cadmium accumulation and adversity physiology. We found that cadmium had the effect of "low-promotion and high-inhibition" on root phenotypes. In addition, the rapid detection of cadmium (Cd), soluble protein (SP), and malondialdehyde (MDA) were achieved based on spectroscopic technology and chemometrics, where the optimal prediction model was least squares support vector machine (LS-SVM) based on the full spectrum (R p =0.9958) for Cd, competitive adaptive reweighted sampling-extreme learning machine (CARS-ELM) (R p =0.9161) for SP and CARS-ELM (R p =0.9021) for MDA, all with R p higher than 0.9. Surprisingly, it took only about 3 min, which was more than 90% reduction in detection time compared with laboratory analysis, demonstrating the excellent ability of spectroscopy for root phenotype detection. These results reveal response mechanism to heavy metal and provide rapid detection method for phenotypic information, which can substantially contribute to crop heavy metal control and food safety supervision., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The limited self-repair capacity of articular cartilage has motivated the development of stem cell therapy based on artificial scaffolds that mimic the extracellular matrix (ECM) of cartilage tissue. In view of the specificity of articular cartilage, desirable tissue adhesiveness and stable mechanical properties under cyclic mechanical loads are critical for cartilage scaffolds. Herein, we developed an injectable and degradable organic-inorganic hybrid hydrogel as a cartilage scaffold based on polyhedral oligomeric silsesquioxane (POSS)-cored polyphosphate and polysaccharide. Specifically, acrylated 8-arm star-shaped POSS-poly(ethyl ethylene phosphate) (POSS-8PEEP-AC) was synthesized and cross-linked with thiolated hyaluronic acid (HA-SH) to form a degradable POSS-PEEP/HA hydrogel. Incorporation of POSS in the hydrogel increased the mechanical properties. The POSS-PEEP/HA hydrogel showed enzymatic biodegradability and favorable biocompatibility, supporting the growth and differentiation of human mesenchymal stem cells (hMSCs). The chondrogenic differentiation of encapsulated hMSCs was promoted by loading transforming growth factor-β 3 (TGF-β 3 ) in the hydrogel. In addition, the injectable POSS-PEEP/HA hydrogel was capable of adhering to rat cartilage tissue and resisting cyclic compression. Furthermore, in vivo results revealed that the transplanted hMSCs encapsulated in the POSS-PEEP/HA hydrogel scaffold significantly improved cartilage regeneration in rats, while the conjugation of TGF-β 3 achieved a better therapeutic effect. The present work demonstrated the potential of the injectable, biodegradable, and mechanically enhanced POSS-PEEP/HA hybrid hydrogel as a scaffold biomaterial for cartilage regeneration.

This review article provides an overview of developments for arterial spin labeling (ASL) perfusion imaging in the body (i.e., outside of the brain). It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. In this review, we focus on specific challenges and developments tailored for ASL in a variety of body locations. After presenting common challenges, organ-specific reviews of challenges and developments are presented, including kidneys, lungs, heart (myocardium), placenta, eye (retina), liver, pancreas, and muscle, which are regions that have seen the most developments outside of the brain. Summaries and recommendations of acquisition parameters (when appropriate) are provided for each organ. We then explore the possibilities for wider adoption of body ASL based on large standardization efforts, as well as the potential opportunities based on recent advances in high/low-field systems and machine-learning. This review seeks to provide an overview of the current state-of-the-art of ASL for applications in the body, highlighting ongoing challenges and solutions that aim to enable more widespread use of the technique in clinical practice., (© 2023 International Society for Magnetic Resonance in Medicine.)

Tumor-associated macrophages (TAMs)-based immunotherapy is a promising strategy. Since TAMs are mainly composed of M2-type macrophages, they have a promoting effect on tumor growth, invasion, and metastasis. M2-type macrophages contain a specific receptor CD163 on their surface, providing a prerequisite for active targeting to TAMs. In this study, we prepared CD163 monoclonal antibody modified doxorubicin-polymer prodrug nanoparticles (abbreviated as mAb-CD163-PDNPs) with pH responsiveness and targeted delivery. First, DOX was bonded with the aldehyde group of a copolymer by Schiff base reaction to form an amphiphilic polymer prodrug, which could self-assemble into nanoparticles in the aqueous solution. Then, mAb-CD163-PDNPs were generated through a "Click" reaction between the azide group on the surface of the prodrug nanoparticles and dibenzocyclocytyl-coupled CD163 monoclonal antibody (mAb-CD163-DBCO). The structure and assembly morphology of the prodrug and nanoparticles were characterized by 1 H NMR, MALDI-TOF MS, FT-IR UV-vis spectroscopy, and dynamic light scattering (DLS). In vitro drug release behavior, cytotoxicity, and cell uptake were also investigated. The results show that the prodrug nanoparticles have regular morphology and stable structure, especially mAb-CD163-PDNPs, which can actively target TAMs at tumor sites, respond to the acidic environment in tumor cells, and release drugs. While depleting TAMs, mAb-CD163-PDNPs can actively enrich drugs at the tumor site and have a strong inhibitory effect on TAMs and tumor cells. The result of the in vivo test also shows a good therapeutic effect, with a tumor inhibition rate of 81%. This strategy of delivering anticancer drugs in TAMs provides a new way to develop targeted drugs for immunotherapy of malignant tumors.

Purpose: To develop a new approach to 3D gradient echo-based anatomical imaging of the neonatal brain with a substantially shorter scan time than standard 3D fast spin echo (FSE) methods, while maintaining a high SNR., Methods: T 2 -prepration was employed immediately prior to image acquisition of 3D balanced steady-state free precession (bSSFP) with a single trajectory of center-out k-space view ordering, which requires no magnetization recovery time between imaging segments during the scan. This approach was compared with 3D FSE, 2D single-shot FSE, and product 3D bSSFP imaging in numerical simulations, plus phantom and in vivo experiments., Results: T 2 -prepared 3D bSSFP generated image contrast of gray matter, white matter, and CSF very similar to that of reference T 2 -weighted imaging methods, without major image artifacts. Scan time of T 2 -prepared 3D bSSFP was remarkably shorter compared to 3D FSE, whereas SNR was comparable to that of 3D FSE and higher than that of 2D single-shot FSE. Specific absorption rate of T 2 -prepared 3D bSSFP remained within the safety limit. Determining an optimal imaging flip angle of T 2 -prepared 3D bSSFP was critical to minimizing blurring of images., Conclusion: T 2 -prepared 3D bSSFP offers an alternative method for anatomical imaging of the neonatal brain with dramatically reduced scan time compared to standard 3D FSE and higher SNR than 2D single-shot FSE., (© 2022 International Society for Magnetic Resonance in Medicine.)

Background: While osteoimmunology interactions between the immune and skeletal systems are known to play an important role in osteoblast development, differentiation and bone metabolism related disease like osteoporosis, such interactions in either bone microenvironment or peripheral circulation in vivo at the single-cell resolution have not yet been characterized., Methods: We explored the osteoimmunology communications between immune cells and osteoblastic lineage cells (OBCs) by performing CellphoneDB and CellChat analyses with single-cell RNA sequencing (scRNA-seq) data from human femoral head. We also explored the osteoimmunology effects of immune cells in peripheral circulation on skeletal phenotypes. We used a scRNA-seq dataset of peripheral blood monocytes (PBMs) to perform deconvolution analysis. Then weighted gene co-expression network analysis (WGCNA) was used to identify monocyte subtype-specific subnetworks. We next used cell-specific network (CSN) and the least absolute shrinkage and selection operator (LASSO) to analyze the correlation of a gene subnetwork identified by WGCNA with bone mineral density (BMD)., Results: We constructed immune cell and OBC communication networks and further identified L-R genes, such as JAG1 and NOTCH1/2, with ossification related functions. We also found a Mono4 related subnetwork that may relate to BMD variation in both older males and postmenopausal female subjects., Conclusions: This is the first study to identify numerous ligand-receptor pairs that likely mediate signals between immune cells and osteoblastic lineage cells. This establishes a foundation to reveal advanced and in-depth osteoimmunology interactions to better understand the relationship between local bone microenvironment and immune cells in peripheral blood and the impact on bone phenotypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Greenbaum, Qiu, Gong, Wang, Lin, Liu, He, Meng, Zhang, Shen, Vemulapalli, Sanchez, Schiller, Xiao and Deng.)

Background: This study aimed to delineate the cell heterogeneity in the bone-implant interface and investigate the fibroblast responses to implant-associated S. aureus infection., Methods: Single-cell RNA sequencing of human periprosthetic tissues from patients with periprosthetic joint infection (PJI, n = 3) and patients with aseptic loosening (AL, n = 2) was performed. Cell type identities and gene expression profiles were analyzed to depict the single-cell landscape in the periprosthetic environment. In addition, 11 publicly available human scRNA-seq datasets were downloaded from GSE datasets and integrated with the in-house sequencing data to identify disease-specific fibroblast subtypes. Furthermore, fibroblast pseudotime trajectory analysis and Single-cell regulatory network inference and clustering (SCENIC) analysis were combined to identify transcription regulators responsible for fibroblast differentiation. Immunofluorescence was performed on the sequenced samples to validate the protein expression of the differentially expressed transcription regulators., Results: Eight major cell types were identified in the human bone-implant interface by analyzing 36,466 cells. Meta-analysis of fibroblasts scRNA-seq data found fibroblasts in the bone-implant interface express a high level of CTHRC1. We also found fibroblasts could differentiate into pro-inflammatory and matrix-producing phenotypes, each primarily presented in the PJI and AL groups, respectively. Furthermore, NPAS2 and TFEC which are activated in PJI samples were suggested to induce pro-inflammatory polarization in fibroblasts, whereas HMX1, SOX5, SOX9, ZIC1, ETS2, and FOXO1 are matrix-producing regulators. Meanwhile, we conducted a CMap analysis and identified forskolin as a potential regulator for fibroblast differentiation toward matrix-producing phenotypes., Conclusions: In this study, we discovered the existence of CTHRC1 + fibroblast in the bone-implant interface. Moreover, we revealed a bipolar mode of fibroblast differentiation and put forward the hypothesis that infection could modulate fibroblast toward a pro-inflammatory phenotype through NPAS2 and TFEC., (© 2023. The Author(s).)

To address large gaps in our understanding of the molecular regulation of articular and growth plate cartilage development in humans, we used our directed differentiation approach to generate these distinct cartilage tissues from human embryonic stem cells. The resulting transcriptomic profiles of hESC-derived articular and growth plate chondrocytes were similar to fetal epiphyseal and growth plate chondrocytes, with respect to genes both known and previously unknown to cartilage biology. With the goal to characterize the regulatory landscapes accompanying these respective transcriptomes, we mapped chromatin accessibility in hESC-derived chondrocyte lineages, and mouse embryonic chondrocytes, using ATAC-sequencing. Integration of the expression dataset with the differentially accessible genomic regions revealed lineage-specific gene regulatory networks. We validated functional interactions of two transcription factors (TFs) (RUNX2 in growth plate chondrocytes and RELA in articular chondrocytes) with their predicted genomic targets. The maps we provide thus represent a framework for probing regulatory interactions governing chondrocyte differentiation. This work constitutes a substantial step towards comprehensive and comparative molecular characterizations of distinct chondrogenic lineages and sheds new light on human cartilage development and biology., Competing Interests: DR, SP, DV, RR, PM, ZL, TC, AC No competing interests declared, (© 2023, Richard, Pregizer et al.)

Background: In recent years, cone-beam computed tomography (CBCT) has played an important role in medical imaging. However, the applications of CBCT are limited due to the severe scatter contamination. Conventional Monte Carlo (MC) simulation can provide accurate scatter estimation for scatter correction, but the expensive computational cost has always been the bottleneck of MC method in clinical application., Purpose: In this work, an MC simulation method combined with a variance reduction technique called correlated sampling is proposed for fast iterative scatter correction., Methods: Correlated sampling exploits correlation between similar simulation systems to reduce the variance of interest quantities. Specifically, conventional MC simulation is first performed on the scatter-contaminated CBCT to generate the initial scatter signal. In the subsequent correction iterations, scatter estimation is then updated by applying correlated MC sampling to the latest corrected CBCT images by reusing the random number sequences of the task-related photons in conventional MC. Afterward, the corrected projections obtained by subtracting the scatter estimation from raw projections are utilized for FDK reconstruction. These steps are repeated until an adequate scatter correction is obtained. The performance of the proposed framework is evaluated by the accuracy of the scatter estimation, the quality of corrected CBCT images and efficiency., Results: Overall, the difference in mean absolute percentage error between scatter estimation with and without correlated sampling is 0.25% for full-fan case and 0.34% for half-fan case, respectively. In simulation studies, scatter artifacts are substantially eliminated, where the mean absolute error value is reduced from 15 to 2 HU in full-fan case and from 53 to 13 HU in half-fan case. Scatter-to-primary ratio is reduced to 0.02 for full-fan and 0.04 for half-fan, respectively. In phantom study, the contrast-to-noise ratio (CNR) is increased by a factor of 1.63, and the contrast is increased by a factor of 1.77. As for clinical studies, the CNR is improved by 11% and 14% for half-fan and full-fan, respectively. The contrast after correction is increased by 19% for half-fan and 44% for full-fan. Furthermore, root mean square error is also effectively reduced, especially from 78 to 4 HU for full-fan. Experimental results demonstrate that the figure of merit is improved between 23 and 43 folds when using correlated sampling. The proposed method takes less than 25 s for the whole iterative scatter correction process., Conclusions: The proposed correlated sampling-based MC simulation method can achieve fast and accurate scatter correction for CBCT, making it suitable for real-time clinical use., (© 2022 American Association of Physicists in Medicine.)

Excessive oil uptake and formation of carcinogens, such as acrylamide (AA), heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs), during deep-frying are a potential threat for food quality and safety. Cellulose- and chitosan-based edible coatings have been widely applied to deep-fried foods for reduction of oil uptake because of their barrier property to limit oil ingress, and their apparent inhibition of AA formation. Cellulose- and chitosan-based edible coatings have low negative impacts on sensory attributes of fried foods and are low cost, nontoxic, and nonallergenic. They also show great potential for reducing HCAs and PAHs in fried foods. The incorporation of nanoparticles improves mechanical and barrier properties of cellulose and chitosan coatings, which may also contribute to reducing carcinogens derived from deep-frying. Considering the potential for positive health outcomes, cellulose- and chitosan-based edible coatings could be a valuable method for the food industry to improve the quality and safety of deep-fried foods., (© 2023 The Authors. Comprehensive Reviews in Food Science and Food Safety published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)