Irisin in thyroid diseases.

Irisin, a hormone-like adipo-myokine, has garnered considerable attention in recent years for its potential impact in metabolic diseases. Its physiological effects are similar to those of thyroid hormones, prompting numerous investigations into potential correlations and interactions between irisin and thyroid function through various in vitro and animal experiments. However, existing studies suggest that the relationship between irisin and thyroid diseases is highly complex and multifaceted. In this paper, we have summarized the research results on serum irisin and thyroid function, providing an overview of advancements and constraints in current research on irisin and thyroid hormones. The aim is to offer insights and directions for future clinical trials in this field.

Pan-cancer characterization of cellular senescence reveals its inter-tumor heterogeneity associated with the tumor microenvironment and prognosis.

Cellular senescence (CS) is characterized by the irreversible cell cycle arrest and plays a key role in aging and diseases, such as cancer. Recent years have witnessed the burgeoning exploration of the intricate relationship between CS and cancer, with CS recognized as either a suppressing or promoting factor and officially acknowledged as one of the 14 cancer hallmarks. However, a comprehensive characterization remains absent from elucidating the divergences of this relationship across different cancer types and its involvement in the multi-facets of tumor development. Here we systematically assessed the cellular senescence of over 10,000 tumor samples from 33 cancer types, starting by defining a set of cancer-associated CS signatures and deriving a quantitative metric representing the CS status, called CS score. We then investigated the CS heterogeneity and its intricate relationship with the prognosis, immune infiltration, and therapeutic responses across different cancers. As a result, cellular senescence demonstrated two distinct prognostic groups: the protective group with eleven cancers, such as LIHC, and the risky group with four cancers, including STAD. Subsequent in-depth investigations between these two groups unveiled the potential molecular and cellular mechanisms underlying the distinct effects of cellular senescence, involving the divergent activation of specific pathways and variances in immune cell infiltrations. These results were further supported by the disparate associations of CS status with the responses to immuno- and chemo-therapies observed between the two groups. Overall, our study offers a deeper understanding of inter-tumor heterogeneity of cellular senescence associated with the tumor microenvironment and cancer prognosis.

Comparative outcomes of surgical and conservative management in carotid artery dissection.

OBJECTIVES: Carotid artery dissection (CAD) is a significant cause of strokes in young individuals, leading to severe complications and socioeconomic burdens. Despite antithrombotic therapy being the primary management strategy, optimal treatment for patients with recurrent or worsening symptoms remains undefined. This study aims to describe the characteristics and evaluate the outcomes of conservative versus surgical management in CAD patients. METHODS: A total of 23 patients presenting with CAD from November 2014 to December 2021 were reviewed retrospectively. Patient demographics, vascular risk factors, symptoms, imaging results, treatment details, and follow-up information were collected and analyzed. Propensity score matching (PSM) was utilized to enhance comparability. RESULTS: The mean age of the patients was 46.4 ± 9.4 years, with a median follow-up of 12 (range 3-90) months. Of the 23 patients reviewed, seven underwent endovascular treatment or open surgery due to unresponsiveness to conservative therapy, while 16 received conservative management. All patients showed regression of symptoms. Surgical patients showed a significant improvement with a 100% patency rate during the follow-up. PS matching adjusted for baseline differences, yielding comparable groups for analysis. No significant difference between treatment approaches was observed in stroke recurrence rates, although surgical intervention showed promising outcomes in symptom resolution and stroke prevention. CONCLUSION: Both conservative and surgical management of CAD can lead to favorable outcomes. While conservative therapy remains the initial approach and proves effective, surgery appears beneficial and safe in certain cases unresponsive to conservative treatment. Further investigation through larger prospective and randomized trials is necessary to establish its safety and efficacy.

Federated learning-based prediction of depression among adolescents across multiple districts in China.

Depression in adolescents is a serious mental health condition that can affect their emotional and social well-being. Detailed understanding of depression patterns and status of depressive symptoms in adolescents could help identify early intervention targets. Despite the growing use of artificial intelligence for diagnosis and prediction of mental health conditions, the traditional centralized machine learning methods require aggregating adolescents' data; this raises concerns about confidentiality and privacy, which hampers the clinical application of machine learning algorithms. In this study, we use federated learning to solve those problems. We included 583,405 middle and high school adolescents from 20 districts in Chengdu China, and collected from three aspects: individuals, families, and schools, containing 11 psychological phenomena to evaluate the status of depressive symptoms. We compared federated and local training frameworks; the results showed the area under the receiver operating characteristic curve for depression increased by up to 20 % (from 0.7544 with local training to 0.9064 with federated training). Moreover, based on the best-performing model, the XGBoost model, we explore the data heterogeneity in federated learning and found that stress, student burnout, and social connection were the three most important predictors of depression symptoms. We then assessed the impact of each subdimension of depression symptoms, results show that sleep was the most impact one which may provide clues to predict depression symptoms in early stage and improve control and prevention efforts.

Application of the "Klotski Technique" in Cervical Ossification of the Posterior Longitudinal Ligament With En Bloc Type Dura Ossification.

OBJECTIVE: The anterior controllable antedisplacement and fusion (ACAF) technique is a new procedure for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) that requires management of the disc adjacent to the ossification. This study describes a novel technique to reduce the number of fixed segments, namely, the "Klotski technique." The efficacy of ACAF using the Klotski technique was compared with that of anterior cervical corpectomy and fusion (ACCF) in the treatment of OPLL with en bloc type dural ossification (DO). METHODS: The clinical data of 25 patients with severe OPLL and en bloc type DO who were treated by the ACAF Klotski technique or ACCF at our hospital from January 2020 to January 2022 were retrospectively analyzed. In the Klotski technique, the number of segments fused within the OPLL is limited. The antedisplacement space was designed according to the shape of the vertebrae-OPLL-DO complex (VODC). Then, the entire VODC was antedisplaced as in Klotski. Neurological function and image examination were assessed preoperatively and postoperatively. Complications associated with surgery were recorded. RESULTS: Patients were followed up for 24-36 months. There were 11 patients who were treated with ACAF and 14 patients who were treated with ACCF. At 2 weeks after surgery, the incidence of neurological deterioration was 21.4% (3 of 14) in the ACCF group and 9.1% (1 of 11) in the ACAF group. The incidence of intraoperative cerebrospinal fluid leakage (CFL) was 35.7% (5 of 14) in the ACCF group and 9.1% (1 of 11) in the ACAF group. The postoperative follow-up JOA scores of the patients in both groups were significantly better than their preoperative JOA scores (p<0.05). CONCLUSION: The Klotski technique for ACAF is a good option for the treatment of patients with en bloc type OPLL-DO, as it limits the number of fused segments, has a low incidence of CFL and neurologic deficits and is associated with good neurological recovery.

An easily fabricated nanoporous Au membrane in drug detection with reusable functionality and high SERS performance.

A method for detecting methamphetamine (MET), ketamine (KET), and morphine (MOP) molecules is presented using a reusable substrate based on SERS. The SERS substrate was prepared by etching the Au/Ag alloy film to synthesize a nanoporous Au membrane (AuNPM). By optimizing the preparation conditions and using rhodamine 6G (R6G) as an analyte, the AuNPM exhibited good SERS performance with a limit of detection (LOD) of 10-9 mol L-1. A competitive immunoassay category has been applied to the detection of MET, KET, and MOP. The MET, KET, and MOP antigens were functionalized on the surface of the AuNPM to specifically bind to the related drug antibodies. The Au nanoparticles (AuNPs) modified with 4-mercaptobenzoic acid (4-MBA) and antibodies against MET, KET, and MOP were used as nanotags. The 4-MBA served as the reporting molecule and drug antibodies were used to bind to free drug molecules in the target solution. The mixture of nanotags and target solution was dropped onto the antigen-modified AuNPM (antigen/AuNPM), and the free nanotags bind to the antigen/AuNPM. By comparing the SERS intensity of 4-MBA with the presence or absence of drug molecules, the drugs were qualitatively and quantitatively identified. Through this category, the LODs for detecting MET, KET, and MOP were 0.1, 1, and 1 ng mL-1, respectively. This study proposes an effective method for constructing SERS-based detection of drug molecules with good potential for practical applications.

The different impacts of pain-related negative emotion and trait negative emotion on brain function in patients with inflammatory bowel disease.

Inflammatory bowel diseases (IBD) are a group of chronic, non-specific intestinal diseases that could comorbid with varieties of negative emotional constructs, including pain-related negative emotions and trait negative emotions; however, the link between brain functions and different dimensions of negative emotions remains largely unknown. Ninety-eight patients with IBD and forty-six healthy subjects were scanned using a 3.0-T functional magnetic resonance imaging scanner. The amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were used to assess resting-state brain activity. Partial least squares (PLS) correlation was employed to assess the relationship among abnormal brain activities, pain-related and trait negative emotions. Compared to controls, patients with IBD exhibited higher values of ALFF in the right anterior cingulate cortex (ACC), lower values of ALFF in the left postcentral gyrus, and higher values of DC in the bilateral ACC. Multivariate PLS correlation analysis revealed the brain scores of the ACC were correlated with pain-related negative emotions, the brain salience in the left postcentral gyrus was associated with the higher-order trait depression. These findings can enhance our comprehension of how pain-related negative emotion and trait negative emotion affect the brains of patients with IBD in distinct ways.

Large animal model species in pluripotent stem cell therapy research and development for retinal diseases: a systematic review.

Aim: Retinal cell therapy modalities, in the category of advanced therapy medicinal products (ATMPs), are being developed to target several retinal diseases. Testing in large animal models (LAMs) is a crucial step in translating retinal ATMPs into clinical practice. However, challenges including budgetary and infrastructure constraints can hinder LAM research design and execution. Here, to facilitate the comparison of the various LAMs in pluripotent retinal cell therapy research, we aimed to systematically evaluate the species distribution, reported scientific utility, and methodology of a range of LAMs. Methods: A systematic search using the words retina, stem cell, transplantation, large animal, pig, rabbit, dog, and nonhuman primate was conducted in the PubMed, Embase, Science Direct and GoogleScholar databases in February 2023. Results: We included 22 studies involving pluripotent stem cells (induced pluripotent stem cells or human embryonic stem cells) in LAMs, including non-human primates (NHP), pigs, dogs, and rabbits. Nearly half of the studies utilized wild-type animal models. In other studies, retinal degeneration features were simulated via laser, chemical, or genetic insult. Transplants were delivered subretinally, either as cell suspensions or pre-formed monolayers (with or without biodegradable scaffolding). The transplanted cells dose per eye varied widely (40,000 - 4,000,000 per dose). Cells were delivered via vitrectomy surgery in 15 studies and by an "ab externo" approach in one study. Structural outcomes were assessed using confocal scanning laser ophthalmoscopy imaging. Functional outcomes included multifocal electroretinogram and, in one case, a measure of visual acuity. Generally, cell suspension transplants exhibited low intraretinal incorporation, while monolayer transplants incorporated more efficiently. Immune responses posed challenges for allogeneic transplants, suggesting that autologous iPSC-derived transplants may be required to decrease the likelihood of rejection. Conclusion: The use of appropriate LAMs helps to advance the development of retinal ATMPs. The anatomical similarity of LAM and human eyes allows the implementation of clinically-relevant surgical techniques. While the FDA Modernization Act 2.0 has provided a framework to consider alternative methods including tissue-on-a-chip and human cell culture models for pharmacologic studies, LAM testing remains useful for cell and tissue replacement studies to inform the development of clinical trial protocols.

Epidemiological characterization of hand, foot, and mouth disease among hospitalized children from 2014 to 2023 in a hospital in Henan Province: Longitudinal surveillance study.

Hand, foot, and mouth disease (HFMD) is an acute infectious illness primarily caused by enteroviruses. The present study aimed to describe the epidemiological characteristics of hospitalized HFMD patients in a hospital in Henan Province (Zhengzhou, China), and to predict the future epidemiological parameters. In this study, we conducted a retrospective analysis of general demographic and clinical data on hospitalized children who were diagnosed with HFMD from 2014 to 2023. We used wavelet analysis to determine the periodicity of the disease. We also conducted an analysis of the impact of the COVID-19 epidemic on the detection ratio of severe illness. Additionally, we employed a Seasonal Difference Autoregressive Moving Average (SARIMA) model to forecast characteristics of future newly hospitalized HFMD children. A total of 19 487 HFMD cases were included in the dataset. Among these cases, 1515 (7.8%) were classified as severe. The peak incidence of HFMD typically fell between May and July, exhibiting pronounced seasonality. The emergence of COVID-19 pandemic changed the ratio of severe illness. In addition, the best-fitted seasonal ARIMA model was identified as (2,0,2)(1,0,1)12. The incidence of severe cases decreased significantly following the introduction of the vaccine to the market (χ2 = 109.9, p < 0.05). The number of hospitalized HFMD cases in Henan Province exhibited a seasonal and declining trend from 2014 to 2023. Non-pharmacological interventions implemented during the COVID-19 pandemic have led to a reduction in the incidence of severe illness.

Impact of the Peripheral Ligand Layer on the Excited-State Deactivation Mechanism of Au38S2(S-Adm)20 and Au30(S-Adm)18 (S-Adm = Adamantanethiolate) Clusters.

Gold nanoclusters are ideal fluorescent labels for biological imaging, disease diagnosis, and treatment. Understanding the origin of the photoluminescence phenomenon in ligand-protected gold nanoclusters is crucial for both basic science and practical applications. In this study, density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were performed to study the mechanism of excited state deactivation of Au38S2(S-Adm)20 and Au30(S-Adm)18 (S-Adm = adamantanethiolate) clusters, which have similar sizes and compositions. The computational results indicate that the differences in structural symmetry and peripheral ligand layer lead to quite different excited state deactivation mechanisms and excited state lifetimes in Au38S2(S-Adm)20 and Au30(S-Adm)18. Specifically, the µ3-S atoms and bridging thiolate (SR) in the ligand layer of Au38S2(S-Adm)20 significantly suppress the structural relaxation of ligand motifs, resulting in a prolonged excited state lifetime and higher quantum yield. For the Au30(S-Adm)18, due to the symmetry forbidden and large structural relaxation of the ligand shell, a rapid nonradiative transition process resulted. This study provides new insights into how the photoluminescence of ligand-protected gold nanoclusters is influenced by their structure and symmetry.

Prognostic nomogram for patients with advanced unresectable hepatocellular carcinoma treated with TAE combined with HAIC.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and often arises in the context of chronic liver disease, such as hepatitis B or C infection, and cirrhosis. Advanced unresectable HCC (uHCC) presents significant treatment challenges due to its advanced stage and inoperability. One efficient treatment method for advanced uHCC is the use of hepatic arterial infusion chemotherapy (HAIC) combined with transcatheter arterial embolization (TAE). Patients and Methods: In this study, we conducted a retrospective collection of clinical data, including basic information, radiological data, and blood test parameters, for patients with advanced uHCC who underwent TAE + HAIC treatment from August 2020 to February 2023. A total of 743 cases involving 262 patients were included. Ultimately, the covariates included in the analysis were the Child-Pugh score, extrahepatic metastasis, tumor number, tumor size, and treatment method. Results: In the study, we performed univariable and multivariable analysis on 23 clinical factors that were screened by LASSO regression, indicating that the five variables aforementionedly were identified as independent factors influencing patient prognosis. Then we developed a nomogram of the sensitive model and calculated concordance indices of prognostic survival models. Conclusion: Based on the uHCC patient cohort, we have developed a prognostic model for OS in patients who received TAE + HAIC treatment. This model can accurately predict OS and has the potential to assist in personalized clinical decision-making.

Zirconium-based nanoclusters as molecular robots for water decontamination.

Water contamination owing to anionic pollutants is a persisting and ubiquitous global threat. The current remediation technologies are mostly low in efficiency, expensive in materials and often associated with complicated processes. Herein, we report a characteristic zirconium-based nanocluster that can work as molecular robots for the efficient remediation of anions-contaminated water with great effectiveness and molecular-level accuracy. It exhibits a stimuli-responsive behavior to facilitate the water treatment process: dissolve in acidic aqueous solutions for molecular-level decontamination and quickly aggregate for post-remediation collection. It can precisely capture the representative anionic pollutants, whilst featuring satisfactory capacities (ca. 175 mg-arsenic/g, 60 mg-chromium/g, 45 mg-fluoride/g, 70 mg-phosphorus/g, respectively), super-fast kinetics (finishing uptake within seconds, which is two to four orders of magnitude faster than typical sorbents), as well as multi-cycle applications without appreciable loss of activity. The coexisting common ions show no effect on the target uptake. The responsible active site investigation shows that four active sites are responsible for the monovalent pollutant removal, and the active sites work in pairs to capture divalent chromate species. Cost analysis shows its economical applicability in practical applications. This work would lead to the development of effective water decontamination with higher effectiveness, more convenience, lower cost and more practical application value.

The Role of FNDC4 in Inflammation and Metabolism for Various Diseases.

Fibronectin (FN) can bind to certain integrin receptors on the cell surface through short peptide sequences, thereby transmitting extracellular stimuli to intracellular effector molecules. FNDC4 plays a similar role due to the constitution of a type III FN domain, which is a binding site for DNA, heparin, or cell surface. It mainly functions as a signal transmitter after being cleaved and secreted as the extracellular N-terminal fibronectin type III domain (sFNDC4). Emerging studies have shown that FNDC4 plays crucial roles in numerous diseases and holds significant implications for guiding clinical treatment. This review aims to summarize the different roles and the latest advances of FNDC4 in the development of various diseases, in order to provide new ideas for clinical treatment.

Direct evidence for selective microbial enrichment with plastic degradation potential in the plastisphere.

Plastisphere, characterized by microbial colonization on plastic debris, has attracted concern with its adverse environmental effects. The microbial features have been increasingly investigated; however, there lacks direct evidence for microplastics serving as carbon sources and enriching plastic-degrading microorganisms. Here, we obtained microbial communities from soil microplastics, analyzed the dissimilarity compared with soil, and characterized the plastic-degrading potential of isolates from plastisphere. Results showed the plastisphere communities significantly differed from soil communities and exhibited a higher relative abundance of Nocardia and Rhodococcus. To verify the selective enrichment of plastic-degrading microorganisms in the plastisphere, culture-based strategies were employed to evaluate the polyethylene (PE) degradation potential of two isolates Nocardia asteroides No.11 and Rhodococcus hoagii No.17. They could grow solely on PE and led to significant weight loss. FTIR and SEM analysis revealed the formation of new functional groups and the destruction of structural integrity on PE surfaces. Genes related to PE biodegradation were identified by genome-wide sequencing thus recognizing relevant enzymes and elucidating potential pathways. Overall, this report combined culture-free and culture-based approaches to confirm the plastic degradation potential of selectively enriched microorganisms in soil plastisphere, providing a positive perspective toward promoting microplastic biodegradation in farmland soil by enhancing natural microbial processes.

The epigenetic-modified downregulation of LOXL1 protein mediates EMT in bladder epithelial cells exposed to benzo[a]pyrene and its metabolite BPDE.

Benzo[a]pyrene (B[a]P) is a well-known polycyclic aromatic hydrocarbon (PAH) pollutant with high carcinogenicity, widespread environmental presence, and significant threat to public health. Epidemiological studies have linked exposure to B[a]P and its metabolite 7,8-dihydroxy-9,10-epoxybenzo[a]pyrene (BPDE) to the development and progression of various cancers, including bladder cancer. However, its underlying mechanism remains unclear. Our study revealed that B[a]P and BPDE induced epithelial-mesenchymal transition (EMT), a critical early event in cell malignant transformation, involving a decrease in E-Cadherin and upregulation of N-Cadherin protein levels, leading to increased cell motility and migration in bladder epithelial cells. Further studies have indicated that LOXL1 DNA undergoes methylation and modification influenced by methyltransferase 3a (DNMT3a) and DNMT3b, resulting in decreased LOXL1 protein levels. The decreased LOXL1 promotes the zinc finger transcription factor SLUG, which then inhibits E-Cadherin protein levels and initiates the EMT process. Moreover, DNMT3a/3b expression appears to be influenced by intracellular oxidative stress levels. These findings suggest that exposure to B[a]P/BPDE promotes the EMT process through the pivotal factor LOXL1, thereby contributing to bladder carcinogenesis. Our study provides a theoretical basis for considering LOXL1 as a potential biomarker for early diagnosis and a novel target for the precise diagnosis and treatment of bladder cancer.

Dapagliflozin suppressed gastric cancer growth via regulating OTUD5 mediated YAP1 deubiquitination.

Gastric cancer (GC) is a common malignant disease that has a fifth highest incidence and fourth highest mortality worldwide. The Warburg effect is a common phenomenon observed in tumors, which suggests that tumor cells would enhance glucose uptake by overexpressing multiple glucose transporters. Sodium glucose transporter 2 (SGLT2) is one of glucose transporters which highly expressed in several cancers, but its role in gastric cancer is still unclear. Our research found that there was a high expression level of SGLT2 in gastric cancer tissues. We found that Dapagliflozin (a SGLT2 inhibitor) could suppress gastric cancer cell proliferation and migration in vitro and tumor growth in vivo. In present study, we revealed how dapagliflozin would suppress gastric cancer progression in a novel mechanism. We proved that dapagliflozin decreased the expression level of OTU deubiquitinase 5 (OTUD5), which further increased the ubiquitination and degradation of YAP1. Overexpression of OTUD5 in gastric cancer cells partly reversed the anti-tumor effect of dapagliflozin. Our findings revealed a novel mechanism by which dapagliflozin has an antitumor effect on gastric cancer and proposed a beneficial strategy for the application of dapagliflozin in gastric cancer patients.

Constructing machine learning models based on non-contrast CT radiomics to predict hemorrhagic transformation after stoke: a two-center study.

Purpose: Machine learning (ML) models were constructed according to non-contrast computed tomography (NCCT) images as well as clinical and laboratory information to assess risk stratification for the occurrence of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients. Methods: A retrospective cohort was constructed with 180 AIS patients who were diagnosed at two centers between January 2019 and October 2023 and were followed for HT outcomes. Patients were analyzed for clinical risk factors for developing HT, infarct texture features were extracted from NCCT images, and the radiomics score (Rad-score) was calculated. Then, five ML models were established and evaluated, and the optimal ML algorithm was used to construct the clinical, radiomics, and clinical-radiomics models. Receiver operating characteristic (ROC) curves were used to compare the performance of the three models in predicting HT. Results: Based on the outcomes of the AIS patients, 104 developed HT, and the remaining 76 had no HT. The HT group consisted of 27 hemorrhagic infarction (HI) and 77 parenchymal-hemorrhage (PH). Patients with HT had a greater neutrophil-to-lymphocyte ratio (NLR), baseline National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and Rad-score and lower Alberta stroke program early CT score (ASPECTS) (all p < 0.01) than patients without HT. The best ML algorithm for building the model was logistic regression. In the training and validation cohorts, the AUC values for the clinical, radiomics, and clinical-radiomics models for predicting HT were 0.829 and 0.876, 0.813 and 0.898, and 0.876 and 0.957, respectively. In subgroup analyses with different treatment modalities, different infarct sizes, and different stroke time windows, the assessment accuracy of the clinical-radiomics model was not statistically meaningful (all p > 0.05), with an overall accuracy of 79.5%. Moreover, this model performed reliably in predicting the PH and HI subcategories, with accuracies of 82.9 and 92.9%, respectively. Conclusion: ML models based on clinical and NCCT radiomics characteristics can be used for early risk evaluation of HT development in AIS patients and show great potential for clinical precision in treatment and prognostic assessment.

Validation of full-length radiograph based musculoskeletal modeling method to estimate medial and lateral knee contact forces.

BACKGROUND: Anatomical parameters of the pelvis, femur, and tibia derived from the full-length radiograph can be used to create a more accurate musculoskeletal model compared to marker-based linear scaling method. However, whether this model leads to more accurate estimations of medial knee contact force (MCF) and lateral knee contact force (LCF) than marker-based linear scaling method is still unknown. RESEARCH QUESTION: This main purpose of this study was to determine whether musculoskeletal model generated from full-length radiograph improves the estimations of MCF and LCF. METHODS: An open-source dataset including marker trajectories, ground reaction forces, in vivo knee contact forces, and full-length radiograph was used to evaluate the accuracy of full-length radiograph musculoskeletal modeling method. Subject-specific musculoskeletal models were created using anatomical parameters derived from the full-length radiograph or marker-based linear scaling methods. MCF and LCF were estimated using musculoskeletal simulations of normal walking trails. The accuracy of modeling methods was determined by comparing the estimated and in vivo measured MCF and LCF. RESULTS: Compared to the marker-based linear scaling approach, the full-length radiograph musculoskeletal modeling method exhibited decreases of 38.3 % and 41.3 % in root mean square error for MCF and LCF respectively, as well as reductions of 50.0 % and 49.3 % in mean peak errors for MCF and LCF respectively. SIGNIFICANCE: The full-length radiograph musculoskeletal modeling method provides a more accurate way to estimate MCF and LCF compared to the traditional maker-based linear scaling approach, which may contribute to understand the initiation, progression, and treatment of OA.

Clinical Efficacy and Safety of transarterial chemoembolization Combined with Targeted Therapy for primary hepatocellular carcinoma.

Objective: To explore the clinical efficacy and safety of transarterial chemoembolization (TACE) combined with targeted therapy for primary hepatocellular carcinoma (PHC). Methods: This was a retrospective study. Retrospective selection of 150 PHC patients admitted to the Renmin Hospital, Hubei University of Medicine January 2019 and June 2021 were included. The patients were divided into the control group and the experimental group according to their treatment regimens. The control group received TACE treatment, while the experimental group received TACE combined with targeted therapy. We analyze the relevant data of two groups of patients and evaluate the clinical efficacy and safety of TACE combined with targeted therapy. Results: The tumor remission rate and control rate in the control group were 41.89% and 75.68%, respectively, while those in the experimental group were 77.63% and 90.79%, with statistically significant differences (p<0.05). The 1-year and 3-year recurrence rates in the control group were 52.71% and 98.65%, respectively, while those in the experimental group were 39.47% and 61.84%, with statistically significant differences (p<0.05). After treatment, the AFP, VEGF, ALT, and AST in the experimental group were significantly reduced compared to the control group (p<0.05). During the treatment period, the incidence and severity of nausea, vomiting, and fever in the experimental group were significantly lower than those in the control group (p<0.05). Conclusion: The clinical efficacy of TACE combined with targeted therapy for PHC is superior to that of TACE alone, with improved disease control rate, improved long-term survival rate, and good safety.

Rubisco packaging and stoichiometric composition of a native ß-carboxysome.

Carboxysomes are anabolic bacterial microcompartments that play an essential role in carbon fixation in cyanobacteria. This self-assembling proteinaceous organelle encapsulates the key CO2-fixing enzymes, Rubisco and carbonic anhydrase, using a polyhedral shell constructed by hundreds of shell protein paralogs. Deciphering the precise arrangement and structural organization of Rubisco enzymes within carboxysomes is crucial for understanding the formation process and overall functionality of carboxysomes. Here, we employed cryo-electron tomography and subtomogram averaging to delineate the three-dimensional packaging of Rubiscos within ß-carboxysomes in the freshwater cyanobacterium Synechococcus elongatus PCC7942 that were grown under low light. Our results revealed that Rubiscos are arranged in multiple concentric layers parallel to the shell within the ß-carboxysome lumen. We also identified the binding of Rubisco with the scaffolding protein CcmM in ß-carboxysomes, which is instrumental for Rubisco encapsulation and ß-carboxysome assembly. Using QconCAT-based quantitative mass spectrometry, we further determined the absolute stoichiometric composition of the entire ß-carboxysome. This study and recent findings on the ß-carboxysome structure provide insights into the assembly principles and structural variation of ß-carboxysomes, which will aid in the rational design and repurposing of carboxysome nanostructures for diverse bioengineering applications.