Dissolved organic matter characteristics linked to bacterial community succession and nitrogen removal performance in woodchip bioreactors.

Woodchip bioreactors are an eco-friendly technology for removing nitrogen (N) pollution. However, there needs to be more clarity regarding the dissolved organic matter (DOM) characteristics and bacterial community succession mechanisms and their association with the N removal performance of bioreactors. The laboratory woodchip bioreactors were continuously operated for 360 days under three influent N level treatments, and the results showed that the average removal rate of TN was 45.80 g N/(m3·day) when the influent N level was 100 mg N/L, which was better than 10 mg N/L and 50 mg N/L. Dynamic succession of bacterial communities in response to influent N levels and DOM characteristics was an important driver of TN removal rates. Medium to high N levels enriched a copiotroph bacterial module (Module 1) detected by network analysis, including Phenylobacterium, Xanthobacteraceae, Burkholderiaceae, Pseudomonas, and Magnetospirillaceae, carrying N-cycle related genes for denitrification and ammonia assimilation by the rapid consumption of DOM. Such a process can increase carbon limitation to stimulate local organic carbon decomposition to enrich oligotrophs with fewer N-cycle potentials (Module 2). Together, this study reveals that the compositional change of DOM and bacterial community succession are closely related to N removal performance, providing an ecological basis for developing techniques for N-rich effluent treatment.

Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202502000-00032/figure1/v/2024-05-28T214302Z/r/image-tiff Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury. Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction. However, the mechanisms involved remain unclear. In this study, we found that after spinal cord injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 and MG3), while resting astrocytes were polarized into reactive and scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury. In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia, and even inhibited the cross-regulation between them. We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway. This, in turn, inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways. In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord, thereby promoting tissue repair and motor function recovery. Overall, Gas6 may play a role in the treatment of spinal cord injury. It can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

TNC upregulation promotes glioma tumourigenesis through TDG-mediated active DNA demethylation.

Gliomas represent the most predominant primary malignant tumor in central nervous system. Thymine DNA glycosylase (TDG) is a central component in active DNA demethylation. However, the specific mechanisms of TDG-mediated active DNA demethylation in gliomas remain unclear. This research indicates TDG expression is overexpressed in gliomas and correlated with poor prognosis. TDG knockdown suppressed the malignant phenotype of gliomas both in vitro and vivo. Notably, RNA-seq analysis revealed a strong association between TDG and tenascin-C (TNC). ChIP-qPCR and MeDIP-qPCR assays were undertaken to confirm that TDG participates in TNC active DNA demethylation process, revealing decreased DNA methylation levels and elevated TNC expression as a result. Silencing TNC expression also suppressed the tumor malignant phenotype in both in vitro and in vivo experiments. Additionally, simultaneous silencing of TNC reduced or even reversed the glioma promotion caused by TDG overexpression. Based on our findings, we conclude that TDG exerts an indispensable role in TNC active DNA demethylation in gliomas. The DNA demethylation process leads to alternations in TNC methylation levels and promotes its expression, thereby contributing to the development of gliomas. These results suggest a novel epigenetic therapeutic strategy targeting active DNA demethylation in gliomas.

Integrating MRI-based radiomics and clinicopathological features for preoperative prognostication of early-stage cervical adenocarcinoma patients: in comparison to deep learning approach.

OBJECTIVES: The roles of magnetic resonance imaging (MRI) -based radiomics approach and deep learning approach in cervical adenocarcinoma (AC) have not been explored. Herein, we aim to develop prognosis-predictive models based on MRI-radiomics and clinical features for AC patients. METHODS: Clinical and pathological information from one hundred and ninety-seven patients with cervical AC was collected and analyzed. For each patient, 107 radiomics features were extracted from T2-weighted MRI images. Feature selection was performed using Spearman correlation and random forest (RF) algorithms, and predictive models were built using support vector machine (SVM) technique. Deep learning models were also trained with T2-weighted MRI images and clinicopathological features through Convolutional Neural Network (CNN). Kaplan-Meier curve was analyzed using significant features. In addition, information from another group of 56 AC patients was used for the independent validation. RESULTS: A total of 107 radiomics features and 6 clinicopathological features (age, FIGO stage, differentiation, invasion depth, lymphovascular space invasion (LVSI), and lymph node metastasis (LNM) were included in the analysis. When predicting the 3-year, 4-year, and 5-year DFS, the model trained solely on radiomics features achieved AUC values of 0.659 (95%CI: 0.620-0.716), 0.791 (95%CI: 0.603-0.922), and 0.853 (95%CI: 0.745-0.912), respectively. However, the combined model, incorporating both radiomics and clinicopathological features, outperformed the radiomics model with AUC values of 0.934 (95%CI: 0.885-0.981), 0.937 (95%CI: 0.867-0.995), and 0.916 (95%CI: 0.857-0.970), respectively. For deep learning models, the MRI-based models achieved an AUC of 0.857, 0.777 and 0.828 for 3-year DFS, 4-year DFS and 5-year DFS prediction, respectively. And the combined deep learning models got a improved performance, the AUCs were 0.903. 0.862 and 0.969. In the independent test set, the combined model achieved an AUC of 0.873, 0.858 and 0.914 for 3-year DFS, 4-year DFS and 5-year DFS prediction, respectively. CONCLUSIONS: We demonstrated the prognostic value of integrating MRI-based radiomics and clinicopathological features in cervical adenocarcinoma. Both radiomics and deep learning models showed improved predictive performance when combined with clinical data, emphasizing the importance of a multimodal approach in patient management.

Br-to-Cl Transformation Guided the Formation of Polyhalogenated Dibenzo-p-dioxins/Dibenzofurans.

Polyhalogenated dibenzo-p-dioxins/dibenzofurans (PXDD/Fs) are commonly released into the environment as byproducts of combustion processes, accompanied by flue gases. Chlorinated (Cl) and brominated (Br) precursors play crucial roles in forming PXDD/Fs. However, the specific contributions of Cl-precursors and Br-precursors to PXDD/Fs formation have not been fully elucidated. Herein, we demonstrate that the formation of Br-precursors can increase the fraction of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) congeners substituted at specific positions, such as 1,2,3,4,6,7,8-HpCDD, OCDD, 2,3,4,7,8-PeCDF, and 2,3,4,6,7,8-HxCDF. This is attributed to the electrophilic chlorination reaction of the Br-precursors, which includes the Br-to-Cl transformation pathway, following the principle of regioselectivity. The observed formation of polybrominated/chlorinated dibenzo-p-dioxins/benzofurans (PBCDD/Fs) from 1,2-dibromobenzene (1,2-DiBBz) as a Br precursor provides direct evidence supporting the proposed Br-to-Cl transformation. Quantum chemical calculations are employed to discuss the principle of regioselectivity in the Br-to-Cl transformation, clarifying the priority of the position for electrophilic chlorination. Additionally, the concentration of PCDD/Fs formed from 1,2-DiBBz is 1.6 µg/kg, comparable to that of polybrominated dibenzo-p-dioxins/dibenzofurans (PBDD/Fs) (2.4 µg/kg), highlighting the potential of brominated organic pollutants as precursors for PCDD/Fs formation. This study provides three potential pathways for PCDD/Fs formation from Br-precursors, establishing a theoretical foundation for elucidating the formation mechanism of PXDD/Fs in the coexistence of Cl and Br.

Clinical characteristics and surgical outcomes of vertebral lesions associated with tumor-induced osteomalacia: report of 16 patients and review of the literature.

Vertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate. PURPOSE: Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods. METHODS: This was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center. RESULTS: Vertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (ß-CTX) levels than the normal range. The sensitivity of 68 Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis. CONCLUSION: 68 Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.

Pioneering noninvasive colorectal cancer detection with an AI-enhanced breath volatilomics platform.

Background: The sensitivity and specificity of current breath biomarkers are often inadequate for effective cancer screening, particularly in colorectal cancer (CRC). While a few exhaled biomarkers in CRC exhibit high specificity, they lack the requisite sensitivity for early-stage detection, thereby limiting improvements in patient survival rates. Methods: In this study, we developed an advanced Mass Spectrometry-based volatilomics platform, complemented by an enhanced breath sampler. The platform integrates artificial intelligence (AI)-assisted algorithms to detect multiple volatile organic compounds (VOCs) biomarkers in human breath. Subsequently, we applied this platform to analyze 364 clinical CRC and normal exhaled samples. Results: The diagnostic signatures, including 2-methyl, octane, and butyric acid, generated by the platform effectively discriminated CRC patients from normal controls with high sensitivity (89.7%), specificity (86.8%), and accuracy (AUC = 0.91). Furthermore, the metastatic signature correctly identified over 50% of metastatic patients who tested negative for carcinoembryonic antigen (CEA). Fecal validation indicated that elevated breath biomarkers correlated with an inflammatory response guided by Bacteroides fragilis in CRC. Conclusion: This study introduces a sophisticated AI-aided Mass Spectrometry-based platform capable of identifying novel and feasible breath biomarkers for early-stage CRC detection. The promising results position the platform as an efficient noninvasive screening test for clinical applications, offering potential advancements in early detection and improved survival rates for CRC patients.

DiffMAR: A Generalized Diffusion Model for Metal Artifact Reduction in CT images.

X-ray imaging frequently introduces varying degrees of metal artifacts to computed tomography (CT) images when metal implants are present. For the metal artifact reduction (MAR) task, existing end-to-end methods often exhibit limited generalization capabilities. While methods based on multiple iterations often suffer from accumulative error, resulting in lower-quality restoration outcomes. In this work, we innovatively present a generalized diffusion model for Metal Artifact Reduction (DiffMAR). The proposed method utilizes a linear degradation process to simulate the physical phenomenon of metal artifact formation in CT images and directly learn an iterative restoration process from paired CT images in the reverse process. During the reverse process of DiffMAR, a Time-Latent Adjustment (TLA) module is designed to adjust time embedding at the latent level, thereby minimizing the accumulative error during iterative restoration. We also designed a structure information extraction (SIE) module to utilize linear interpolation data in the image domain, guiding the generation of anatomical structures during the iterative restoring. This leads to more accurate and robust shadow-free image generation. Comprehensive analysis, including both synthesized data and clinical evidence, confirms that our proposed method surpasses the current state-of-the-art (SOTA) MAR methods in terms of both image generation quality and generalization.

A generalist vision-language foundation model for diverse biomedical tasks.

Traditional biomedical artificial intelligence (AI) models, designed for specific tasks or modalities, often exhibit limited flexibility in real-world deployment and struggle to utilize holistic information. Generalist AI holds the potential to address these limitations due to its versatility in interpreting different data types and generating tailored outputs for diverse needs. However, existing biomedical generalist AI solutions are typically heavyweight and closed source to researchers, practitioners and patients. Here, we describe BiomedGPT, the first open-source and lightweight vision-language foundation model, designed as a generalist capable of performing various biomedical tasks. BiomedGPT achieved state-of-the-art results in 16 out of 25 experiments while maintaining a computing-friendly model scale. We also conducted human evaluations to assess the capabilities of BiomedGPT in radiology visual question answering, report generation and summarization. BiomedGPT exhibits robust prediction ability with a low error rate of 3.8% in question answering, satisfactory performance with an error rate of 8.3% in writing complex radiology reports, and competitive summarization ability with a nearly equivalent preference score to human experts. Our method demonstrates that effective training with diverse data can lead to more practical biomedical AI for improving diagnosis and workflow efficiency.

CircUGP2 Suppresses Intrahepatic Cholangiocarcinoma Progression via p53 Signaling Through Interacting With PURB to Regulate ADGRB1 Transcription and Sponging miR-3191-5p.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and its prognosis remains poor. Although growing numbers of studies have verified the involvement of circular RNAs (circRNAs) in various cancer types, their specific functions in ICC remain elusive. Herein, a circRNA, circUGP2 is identified by circRNA sequencing, which is downregulated in ICC tissues and correlated with patients' prognosis. Moreover, circUGP2 overexpression suppresses tumor progression in vitro and in vivo. Mechanistically, circUGP2 functions as a transcriptional co-activator of PURB over the expression of ADGRB1. It can also upregulate ADGRB1 expression by sponging miR-3191-5p. As a result, ADGRB1 prevents MDM2-mediated p53 polyubiquitination and thereby activates p53 signaling to inhibit ICC progression. Based on these findings, circUGP2 plasmid is encapsulated into a lipid nanoparticle (LNP) system, which has successfully targeted tumor site and shows superior anti-tumor effects. In summary, the present study has identified the role of circUGP2 as a tumor suppressor in ICC through regulating ADGRB1/p53 axis, and the application of LNP provides a promising translational strategy for ICC treatment.

The control mechanism of P-wave attenuation in unconsolidated porous media.

Unconsolidated porous media are distinct from consolidated porous rocks in the negligible bulk and shear moduli. This paper is motivated by resolving the control mechanism of P-wave attenuation in the media (represented by Toyoura sands and glass beads) saturated with water. The first model is Biot theory in which longitudinal friction (arising from velocity difference between the two phases) is quantified using dynamic permeability as a function of frequency. The first model simulates phase velocity (Vp) and the ultrasonically measured quality factor (Qp) well. A second model is the transverse squirt model in which squirt is induced by pressure differential between contact of grains (COG) and the main pore space. The second model outputs unrealistic Vp and Qp. The results reveal that P-wave attenuation in unconsolidated porous media (saturated with water) is governed by longitudinal friction rather than intrapore squirt. Remarkably, low-frequency dynamic permeability is much smaller than Darcy permeability, indicating that ultrasonic P-wave is surprisingly capable of indirectly detecting the very narrow gap at COG.

EphA3 CAR T cells are effective against glioblastoma in preclinical models.

BACKGROUND: Adoptive T-cell therapy targeting antigens expressed in glioblastoma has emerged as a potential therapeutic strategy to prevent or delay recurrence and prolong overall survival in this aggressive disease setting. Ephrin receptor A3 (EphA3), which is highly expressed in glioblastoma; in particular, on the tumor vasculature and brain cancer stem cells, is an ideal target for immune-based therapies. METHODS: We have designed an EphA3-targeted chimeric antigen receptor (CAR) using the single chain variable fragment of a novel monoclonal antibody, and assessed its therapeutic potential against EphA3-expressing patient-derived glioblastoma neurospheres, organoids and xenografted glioblastoma tumors in immunodeficient mice. RESULTS: In vitro expanded EphA3 CAR T cells from healthy individuals efficiently recognize and kill EphA3-positive glioblastoma cells in vitro. Furthermore, these effector cells demonstrated curative efficacy in an orthotopic xenograft model of glioblastoma. EphA3 CAR T cells were equally effective in targeting patient-derived neurospheres and infiltrate, disaggregate, and induce apoptosis in glioblastoma-derived organoids. CONCLUSIONS: This study provides compelling evidence supporting the therapeutic potential of EphA3 CAR T-cell therapy against glioblastoma by targeting EphA3 associated with brain cancer stem cells and the tumor vasculature. The ability to target patient-derived glioblastoma underscores the translational significance of this EphA3 CAR T-cell therapy in the pursuit of effective and targeted glioblastoma treatment strategies.

Identification and prediction of frailty among community-dwelling older Japanese adults based on Bayesian network analysis: a cross-sectional and longitudinal study.

BACKGROUND: Frailty is a multifactorial syndrome; through this study, we aimed to investigate the physiological, psychological, and social factors associated with frailty and frailty worsening in community-dwelling older adults. METHODS: We conducted a cross-sectional and longitudinal study using data from the "Community Empowerment and Well-Being and Healthy Long-term Care: Evidence from a Cohort Study (CEC)," which focuses on community dwellers aged 65 and above in Japan. The sample of the cross-sectional study was drawn from a CEC study conducted in 2014 with a total of 673 participants. After excluding those who were frail during the baseline assessment (2014) and at the 3-year follow-up (2017), the study included 373 participants. Frailty assessment was extracted from the Kihon Checklist, while social relationships were assessed using the Social Interaction Index (ISI). Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression and their predictive abilities were tested. Factors associated with frailty status and worsening were identified through the Maximum-min Hillclimb algorithm applied to Bayesian networks (BNs). RESULTS: At baseline, 14.1% (95 out of 673) participants were frail, and 24.1% (90 out of 373) participants experienced frailty worsening at the 3-years follow up. LASSO regression identified key variables for frailty. For frailty identification (cross-sectional), the LASSO model's AUC was 0.943 (95%CI 0.913-0.974), indicating good discrimination, with Hosmer-Lemeshow (H-L) test p = 0.395. For frailty worsening (longitudinal), the LASSO model's AUC was 0.722 (95%CI 0.656-0.788), indicating moderate discrimination, with H-L test p = 0.26. The BNs found that age, multimorbidity, function status, and social relationships were parent nodes directly related to frailty. It revealed an 85% probability of frailty in individuals aged 75 or older with physical dysfunction, polypharmacy, and low ISI scores; however, if their social relationships and polypharmacy status improve, the probability reduces to 50.0%. In the longitudinal-level frailty worsening model, a 75% probability of frailty worsening in individuals aged 75 or older with declined physical function and ISI scores was noted; however, if physical function and ISI improve, the probability decreases to 25.0%. CONCLUSION: Frailty and its progression are prevalent among community-dwelling older adults and are influenced by various factors, including age, physical function, and social relationships. BNs facilitate the identification of interrelationships among these variables, quantify the influence of key factors. However, further research is required to validate the proposed model.

Fluoride induces hepatointestinal damage and vitamin B2 mitigation by regulating IL-17A and Bifidobacterium in ileum.

INTRODUCTION: Fluorosis is a global public health disease affecting more than 50 countries and 500 million people. Excessive fluoride damages the liver and intestines, yet the mechanisms and therapeutic approaches remain unclear. OBJECTIVES: To explore the mechanisms by which fluoride-induced intestinal-hepatic damage and vitamin B2 alleviation. METHODS: Fluoride and/or vitamin B2-treated IL-17A knockout and wild-type mouse models were established, the morphological and functional changes of liver and gut, total bile acid biosynthesis, metabolism, transport, and regulation of FXR-FGF15 signaling pathways were evaluated, the ileal microbiome was further analyzed by 16S rDNA sequence. Finally, Bifidobacterium supplementation mouse model was designed and re-examined the above indicators. RESULTS: The results demonstrated that fluoride induced hepatointestinal injury and enterohepatic circulation disorder by altering the synthesis, transporters, and FXR-FGF15 pathway regulation of total bile acid. Importantly, the ileum was found to be the most sensitive and fluoride changed ileal microbiome particularly by reducing abundance of Bifidobacterium. While vitamin B2 supplementation attenuated fluoride-induced enterohepatic circulation dysfunction through IL-17A and ileal microbiome, Bifidobacterium supplementation also reversed fluoride-induced hepatointestinal injury. CONCLUSION: Fluoride induces morphological and functional impairment of liver and gut tissues, as well as enterohepatic circulation disorder by altering total bile acid (TBA) synthesis, transporters, and FXR-FGF15 signaling regulation. Vitamin B2 attenuated fluoride-induced enterohepatic circulation disorder through IL-17A knockout and ileal microbiome regulation. The ileum was found to be the most sensitive to fluoride, leading to changes in ileal microbiome, particularly the reduction of Bifidobacterium. Furthermore, Bifidobacterium supplementation reversed fluoride-induced hepatointestinal injury. This study not only elucidates a novel mechanism by which fluoride causes hepatointestinal toxicity, but also provides a new physiological function of vitamin B2, which will be useful in the therapy of fluorosis and other hepatoenterological diseases.

Identification of characteristic flavor quality of ceramic-pot sealed meat after reheating based on HS-GC-IMS, bionic sensory combined chemometrics.

This study investigated the impacts of microwave reheating (MR), boil reheating (BR), and steam reheating (SR) on the flavor profile of Ceramic-Pot Sealed Meat (CPSM). Electronic nose and tongue revealed that the microwaving was superior in preserving the original olfactory and gustatory profiles of CPSM compared to the other methods. Headspace- Gas chromatography- ion mobility spectrometry (HS-GC-IMS) detected 48 compounds, encompassing 15 alcohols, 11 aldehydes, 9 ketones, 7 esters, 2 alkenes, and 2 others, 1 acid. Spectral and clustering analysis revealed a significant rise in the content of Warmed-over flavor compounds after boil reheating, culminating in pronounced flavor distortion and a decline in sensory scores. Relative odor activity value (ROAV) and chemometrics identified nine substances as the principal flavor compounds responsible to flavor distortion. In conclusion, all reheating methods induce changes in the original flavor characteristics profiles of CPSM. However, microwave reheating offers superior preservation of the flavor characteristics of CPSM.

Temporomandibular Joint Disorders and Pain Confounders: An Awareness Study.

OBJECTIVES: Temporomandibular disorders (TMD) are the most common nonodontogenic cause of orofacial pain, leading to morbidity and impairment. TMD presents a diagnostic challenge due to many aetiologies that exhibit comparable symptoms and refer pain to the temporomandibular joint (TMJ) region. Patients may be referred to dental specialists without accounting for all pain sources. This study aims to identify radiographic confounders (RCs) that can be mistaken for TMD in patients undergoing TMJ assessment using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: A review of 369 CBCT oral maxillofacial radiology reports of the TMJ acquired between July 2020 and June 2023 was completed. Pertinent RCs were classified as endodontic lesions, impacted dentition, sinus pathologies, root fractures, soft tissue calcifications, and others. The chi-squared test assessed the significance of the relationship between RCs and patient variables. RESULTS: A total of 283 RCs were identified in 202 of the 369 cases (54.7%). The most frequent findings included sinus abnormalities (32.5%), endodontic lesions (15.2%), impacted dentition (12.7%), and elongated/calcified stylohyoid process (9.2%). Significant associations were found between sinus pathologies with TMD signs (P = .009) and gender (P = .001). CONCLUSION: Our results indicate that RCs that mimic TMD-related symptoms are prevalent in patients referred for TMJ CBCT imaging. CLINICAL RELEVANCE: Clinicians should be aware of these RCs when diagnosing complaints related to the TMJ. We recommend clinicians first obtain dental clearance and investigate all other potential sources of a patient's complaint before initiating referrals to avoid unnecessary costs and delays in patient care.

SMYD5 is a ribosomal methyltransferase that catalyzes RPL40 lysine methylation to enhance translation output and promote hepatocellular carcinoma.

While lysine methylation is well-known for regulating gene expression transcriptionally, its implications in translation have been largely uncharted. Trimethylation at lysine 22 (K22me3) on RPL40, a core ribosomal protein located in the GTPase activation center, was first reported 27 years ago. Yet, its methyltransferase and role in translation remain unexplored. Here, we report that SMYD5 has robust in vitro activity toward RPL40 K22 and primarily catalyzes RPL40 K22me3 in cells. The loss of SMYD5 and RPL40 K22me3 leads to reduced translation output and disturbed elongation as evidenced by increased ribosome collisions. SMYD5 and RPL40 K22me3 are upregulated in hepatocellular carcinoma (HCC) and negatively correlated with patient prognosis. Depleting SMYD5 renders HCC cells hypersensitive to mTOR inhibition in both 2D and 3D cultures. Additionally, the loss of SMYD5 markedly inhibits HCC development and growth in both genetically engineered mouse and patient-derived xenograft (PDX) models, with the inhibitory effect in the PDX model further enhanced by concurrent mTOR suppression. Our findings reveal a novel role of the SMYD5 and RPL40 K22me3 axis in translation elongation and highlight the therapeutic potential of targeting SMYD5 in HCC, particularly with concurrent mTOR inhibition. This work also conceptually broadens the understanding of lysine methylation, extending its significance from transcriptional regulation to translational control.

A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2.

Liver fibrosis is an urgent clinical problem without effective therapies. Here we conducted a high-content screening on a natural Euphorbiaceae diterpenoid library to identify a potent anti-liver fibrosis lead, 12-deoxyphorbol 13-palmitate (DP). Leveraging a photo-affinity labeling approach, apolipoprotein L2 (APOL2), an endoplasmic reticulum (ER)-rich protein, was identified as the direct target of DP. Mechanistically, APOL2 is induced in activated hepatic stellate cells upon transforming growth factor-ß1 (TGF-ß1) stimulation, which then binds to sarcoplasmic/ER calcium ATPase 2 (SERCA2) to trigger ER stress and elevate its downstream protein kinase R-like ER kinase (PERK)-hairy and enhancer of split 1 (HES1) axis, ultimately promoting liver fibrosis. As a result, targeting APOL2 by DP or ablation of APOL2 significantly impairs APOL2-SERCA2-PERK-HES1 signaling and mitigates fibrosis progression. Our findings not only define APOL2 as a novel therapeutic target for liver fibrosis but also highlight DP as a promising lead for treatment of this symptom.

Customized Modification of Welan Gum Properties Through Controllable Grafting of Acrylamide.

Welan gum (WG) has a wide range of applications, but it is not yet suitable for applications such as oil recovery profile control that have complex requirements for viscosity, gelation properties, and so forth. Grafting modification is an important strategy for improving the property of WG, but there are few reports on controllable modification of WG to customize it for specific application. Acrylamide (AM) dosage was identified as the key factor affecting the grafting ratio of AM onto WG by a uniform experimental design. The grafting ratio can be directly adjusted between 99% and 378% based on the positive correlation with dosage of AM, and viscosity can be adjusted between 206 and 327 mPa s based on the negative correlation with grafting ratio. The 50% weight loss temperature of W11 with a grafting ratio of 110% raised from 314 to 336°C after grafting. The viscosity of the hydrogel formed with WG11 reached 15,654 mPa s, nearly nine times higher than that of unmodified WG. In addition, the gelation time can be controlled within 5 days, so that it can be injected to the optimal area in oilfield profile, avoiding pipeline blockage. This study enables adjusting viscosity of WG grafted with AM by controlling the grafting rate, and enhances gelation performance and thermal stability of WG, which will expand the application of WG in oil recovery and other fields.

Sex differences in circulating metabolites across glycemic status and risk of coronary heart disease.

Background: Women with type 2 diabetes (T2D) have a 50% excess risk of coronary heart disease (CHD) than men with T2D. We compared circulating metabolites and their associations with CHD in men and women across glycemic status. Methods: We used metabolomic data (lipoproteins, fatty acids, amino acids, glycolysis, ketones, inflammation, and fluid balance) for 87,326 CHD-free UK Biobank participants. We used linear regressions to examine the association of sex and metabolites (log) in newly diagnosed T2D (diagnosis<2 yrs from baseline), prediabetes (A1c 5.7-6.5%), and euglycemia, accounting for age, race, Deprivation Index, income, smoking, alcohol drinking, obesity, physical activity, medications for hypertension, hyperlipidemia, and diabetes. We used Cox models to evaluate the association of metabolites and CHD risk by sex, adjusting the same covariates and menopausal status (women). All analyses were FDR-adjusted. Findings: We included 1250 individuals with new T2D, 12,706 with prediabetes, and 83,315 with euglycemia. In adjusted linear regressions, women showed a progressive increase in atherogenic lipid and lipoprotein markers and inflammatory marker, glycoprotein acetyls, compared to men as their glycemic status advanced. However, women had lower levels of albumin during this transition. Menopausal status did not alter these sex differences. In a 10-year follow-up, an SD higher total TG, TG in VLDL, LDL, and HDL, saturated fatty acids (SFA) were positively associated with a higher risk of CHD in women with T2D but not in men (p-interactions 0.03-0.15). Interpretation: With advancing glycemic status, women exhibited higher levels of atherogenic lipids and lipoproteins, as well as inflammatory markers, but lower circulating albumin. Women with T2D appear to be at a higher risk of CHD associated with TG, VLDL-TG, LDL-TG, and HDL-TG, and SFA than men with T2D.