Model Properties and Clinical Application in the Finite Element Analysis of Knee Joint: A Review.

The knee is the most complex joint in the human body, including bony structures like the femur, tibia, fibula, and patella, and soft tissues like menisci, ligaments, muscles, and tendons. Complex anatomical structures of the knee joint make it difficult to conduct precise biomechanical research and explore the mechanism of movement and injury. The finite element model (FEM), as an important engineering analysis technique, has been widely used in many fields of bioengineering research. The FEM has advantages in the biomechanical analysis of objects with complex structures. Researchers can use this technology to construct a human knee joint model and perform biomechanical analysis on it. At the same time, finite element analysis can effectively evaluate variables such as stress, strain, displacement, and rotation, helping to predict injury mechanisms and optimize surgical techniques, which make up for the shortcomings of traditional biomechanics experimental research. However, few papers introduce what material properties should be selected for each anatomic structure of knee FEM to meet different research purposes. Based on previous finite element studies of the knee joint, this paper summarizes various modeling strategies and applications, serving as a reference for constructing knee joint models and research design.

Single-cell RNA sequencing reveals the impact of mechanical loading on knee tibial cartilage in osteoarthritis.

Articular cartilage degeneration is one of the major pathogenic alterations observed in knee osteoarthritis (KOA). Mechanical stress has been verified to contribute to KOA development. To gain insight into the pathogenic mechanism of KOA development, we investigated chondrocyte subsets under different mechanical loading conditions via single-cell RNA sequencing (scRNA-seq). Articular cartilage tissues from both high mechanical loading (named the OATL group) and low mechanical loading (named the OATN group) surfaces were obtained from the proximal tibia of KOA patients, and scRNA-seq was conducted. Chondrocyte subtypes, including a new subset, HTC-C (hypertrophic chondrocytes-C), and their functions, development and interactions among cell subsets were identified. Immunohistochemical staining was also conducted to verify the existence and location of each chondrocyte subset. Furthermore, differentially expressed genes (DEGs) and their functions between regions with high and low mechanical loading were identified. Based on Gene Ontology terms for the DEGs in each cell type, the characteristic of cartilage degeneration in the OATL region was clarified. Mitochondrial dysfunction may be involved in the KOA process in the OATN region.

Single-cell RNA sequencing reveals differences between force application and bearing in ankle cartilage.

Chondrocytes are the major functional elements of articular cartilage. Force has been demonstrated to influence the structure and function of articular cartilage and chondrocytes. Therefore, it is necessary to evaluate chondrocytes under different force conditions to gain deep insight into chondrocyte function. Six cartilage tissues from the distal tibia (referred to as the AT group) and five cartilage tissues from the trochlear surface of the talus (referred to as the ATa group) were obtained from 6 donors who had experienced fatal accidents. Single-cell RNA sequencing was used on these samples. A total of 149,816 cells were analyzed. Nine chondrocyte subsets were ultimately identified. Pseudotime analyses, enrichment analyses, cell-cell interaction studies, and single-cell regulatory network inference and clustering were performed for each cell type, and the differences between the AT and ATa groups were analyzed. Immunohistochemical staining was used to verify the existence of each chondrocyte subset and its distribution. The results suggested that reactive oxygen species related processes were active in the force-applied region, while tissue repair processes were common in the force-bearing region. Although the number of prehypertrophic chondrocytes was small, these chondrocytes seemed to play an important role in the ankle.

Sarcopenia and myosteatosis diagnostic tool for gastrointestinal cancer: creatinine to cystatin C ratio as evaluation marker.

OBJECTIVE: This study aimed to develop a simplified diagnostic tool for assessing sarcopenia and myosteatosis in gastrointestinal cancer patients, focusing on the creatinine to cystatin C ratio (CCR) as an evaluation marker. METHODS: 955 patients were split into training (n = 671) and validation (n = 284) cohorts. Using logistic regression, risk factors for sarcopenia and myosteatosis were identified. The predictive capacity of the developed model was examined. The association between CCR and muscle imaging parameters, along with its impact on clinical outcomes, was analyzed. RESULTS: No significant differences were observed in baseline traits between cohorts. CCR emerged as a significant risk factor for both sarcopenia and myosteatosis. Nomograms for diagnosing these conditions demonstrated strong predictive ability, with AUC values indicating high accuracy (sarcopenia AUC: 0.865-0.872; myosteatosis AUC: 0.848-0.849). The clinical utility of the nomograms was confirmed through decision curve analysis. CCR showed significant association with muscle imaging parameters and was a reliable indicator for assessing the risk of sarcopenia, myosteatosis, and cachexia. Moreover, CCR was able to differentiate between patient survival and disease progression rates. CONCLUSION: A diagnostic tool for sarcopenia and myosteatosis in gastrointestinal cancer patients was developed, with CCR being a pivotal biomarker for disease diagnosis and prognosis prediction.

Single-cell RNA sequencing reveals distinct chondrocyte states in femoral cartilage under weight-bearing load in Rheumatoid arthritis.

Introduction: Rheumatoid arthritis (RA) is a common autoimmune joint disease, the pathogenesis of which is still unclear. Cartilage damage is one of the main manifestations of the disease. Chondrocytes are the main functional component of articular cartilage, which is relevant to disease progression. Mechanical loading affects the structure and function of articular cartilage and chondrocytes, but the effect of weight bearing on chondrocytes in rheumatoid arthritis is still unclear. Methods: In this paper, single-cell RNA sequencing (scRNA-seq) was performed on collected cartilage from the weight-bearing region (Fb group) and non-weight-bearing region (Fnb group) of the femur, and the differences between the Fb and Fnb groups were analyzed by cell type annotation, pseudotime analysis, enrichment analysis, cell interactions, single-cell regulatory network inference and clustering (SCENIC) for each cell type. Results: A total of 87,542 cells were analyzed and divided into 9 clusters. Six chondrocyte subpopulations were finally identified by cellular annotation, and two new chondrocyte subtypes were annotated as immune-associated chondrocytes. The presence of each chondrocyte subpopulation and its distribution were verified using immunohistochemical staining (IHC). In this study, the atlas of femoral cartilage in knee rheumatoid arthritis and 2 new immune-related chondrocytes were validated using scRNA-seq and IHC, and chondrocytes in the weight-bearing and non-weight-bearing regions of the femur were compared. There might be a process of macrophage polarization transition in MCs in response to mechanical loading, as in macrophages. Conclusion: Two new immune-associated chondrocytes were identified. MCs have contrasting functions in different regions, which might provide insight into the role of immune and mechanical loading on chondrocytes in the development of knee rheumatoid osteoarthritis.

Mitophagy-mediated inflammation and oxidative stress contribute to muscle wasting in cancer cachexia.

Cancer cachexia is commonly seen in patients with malignant tumors, which usually leads to poor life quality and negatively affects long-term prognosis and survival. Mitochondria dysfunction and enhanced autophagy are well-established to play an important role in skeletal muscle wasting. However, whether mitophagy is engaged in the pathogenesis of cancer cachexia requires further investigation. This study comprised a clinical study and animal experimentation. Clinical data such as CT images and laboratory results were obtained and analyzed. Then mice model of cancer cachexia and mitophagy inhibition were established. Data including skeletal muscle mass and function, mitochondria structure and function, inflammatory factors as well as ROS concentration. Mitophagy was enhanced in cancer cachexia patients with increased inflammatory factors. Greater disruption of skeletal muscle fiber and mitochondria structure were seen in cancer cachexia, with a higher level of inflammatory factors and ROS expression in skeletal muscle. Meanwhile, ATP production was undermined, indicating a close relationship with mitophagy, inflammation, and oxidative stress in the skeletal muscle of cancer cachexia mice models. In conclusion, mitophagy is activated in cancer cachexia and may play a role in skeletal muscle atrophy, and inflammation and oxidative stress might participate in mitophagy-related skeletal muscle injury.

Development and application of the Cancer Cachexia Staging Index for the diagnosis and staging of cancer cachexia.

OBJECTIVE: The current tools for evaluating cancer cachexia are either too simple to reflect the far-reaching effects of cachexia or too complicated to be used in daily practice. This study aimed to develop a cancer cachexia staging index (CCSI) that is both practical and comprehensive. METHODS: Patients with gastrointestinal cancers were prospectively included in the study. Clinical data including weight change, body composition, systematic inflammation, nutrition, and function status were entered into regression models to determine the best variable combination as well as their respective cutoff values and score distribution in the CCSI. The CCSI's ability to predict outcomes and evaluate the consequences of cachexia for patients were then assessed. RESULTS: Clinical information and test results from 10 568 patients were used to develop a CCSI composed of subjective and objective measures. Subjective measures included body mass index-adjusted weight loss grade, rate of weight loss, inflammation (neutrophil-to-lymphocyte ratio and C-reactive protein level), and prealbumin level. Objective measures included appetite status and physical status. Patients were diagnosed and stratified by the total CCSI score into 3 subgroups: no cachexia, mild or moderate cachexia, and severe cachexia. The CCSI grades showed good survival discrimination and were independently predictive of survival in multivariate analysis. Compared with the traditional Fearon criteria for diagnosing cancer cachexia, the CCSI was more accurate in predicting postoperative complications (net reclassification index [NRI], 2.8%; 95% CI, 0.0104-0.0456%), death (NRI, 10.68%; 95% CI, 0.0429-0.1708%), recurrence (NRI, 3.71%; 95% CI, 0.0082-0.0685%), and overall survival (NRI, 8.5%; 95% CI, 0.0219-0.1533%). The CCSI also had better discriminative ability than Fearon criteria in discriminating nutritional status, body composition, and systematic inflammation in patients with or without cachexia. A more detailed evaluation of a randomly selected subgroup (n = 1566) showed that CCSI grades had good discrimination of appetite and food intake status, physical function and muscle strength, symptom burden, and quality of life. CONCLUSIONS: The CCSI is a comprehensive and practical evaluation tool for cancer cachexia. It can predict postoperative outcomes and survival. The CCSI stages showed good discrimination when evaluating patients with cancer in terms of nutritional status, physical function, systematic inflammation, body composition, symptom burden, and quality of life.

Efficacy of acupuncture for the treatment of Parkinson's disease-related constipation (PDC): A randomized controlled trial.

Objective: To evaluate the efficacy of acupuncture in treating Parkinson's disease-related constipation (PDC). Materials and methods: This was a randomized, controlled trial in which patients, outcome assessors, and statisticians were all blinded. Seventy-eight eligible patients were randomly assigned to either the manual acupuncture (MA) or sham acupuncture (SA) groups and received 12 sessions of treatment over a 4-week period. Following treatment, patients were monitored until the eighth week. The primary outcome was the change in weekly complete spontaneous bowel movements (CSBMs) from baseline after treatment and follow-up. The Constipation Symptom and Efficacy Assessment Scale (CSEAS), the Patient-Assessment of Constipation Quality of Life questionnaire (PAC-QOL), and the Unified Parkinson's Disease Rating Scale (UPDRS) were used as secondary outcomes. Results: In the intention-to-treat analysis, 78 patients with PDC were included, with 71 completing the 4-week intervention and 4-week follow-up. When compared to the SA group, weekly CSBMs were significantly increased after treatment with the MA group (P < 0.001). Weekly CSBMs in the MA group were 3.36 [standard deviation (SD) 1.44] at baseline and increased to 4.62 (SD, 1.84) after treatment (week 4). The SA group's weekly CSBMs were 3.10 (SD, 1.45) at baseline and 3.03 (SD, 1.25) after treatment, with no significant change from baseline. The effect on weekly CSBMs improvement in the MA group lasted through the follow-up period (P < 0.001). Conclusion: Acupuncture was found to be effective and safe in treating PDC in this study, and the treatment effect lasted up to 4 weeks. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR2200059979.

Development and validation of a cancer cachexia risk score for digestive tract cancer patients before abdominal surgery.

BACKGROUND: Cancer cachexia is prevalent in digestive tract cancer patients and has significant impacts on prognosis; it is vital to identify individuals who are at risk of cancer cachexia to allow for appropriate evaluation and treatment. This study evaluated whether digestive tract cancer patients with a risk of cancer cachexia and who had a risk of adverse survival could be identified before abdominal surgery. METHODS: This large-scale cohort study involved patients who underwent abdominal surgery between January 2015 and December 2020 to treat digestive tract cancer. Participants were allocated to the development cohort, the validation cohort, or the application cohort. Univariate and multivariate analyses of the development cohort were performed to detect distinct risk variables for cancer cachexia to create a cancer cachexia risk score. The performance of the risk score across all the three cohorts was assessed through calculating the area under the receiver operating characteristic curve (AUC), as well as calibration and decision curves. We tested how well the score predicted survival outcomes in the application cohort. RESULTS: A total of 16 264 patients (median 64 years of age; 65.9% male) were included, with 8743 in the development cohort, 5828 in the validation cohort, and 1693 in the application cohort. Seven variables were identified as independent predictive factors and were included in the cancer cachexia risk score: cancer site, cancer stage, time from symptom onset to hospitalization, appetite loss, body mass index, skeletal muscle index, and neutrophil-lymphocyte ratio. The risk score predicting cancer cachexia owns a good discrimination, with the mean AUC of 0.760 (P < 0.001) in the development cohort, 0.743 (P < 0.001) in the validation cohort, and 0.751 (P < 0.001) in the application cohort, respectively, and had an excellent calibration (all P > 0.05). The decision curve analysis revealed net benefits of the risk score across a range of risk thresholds in the three cohorts. In the application cohort, compared with the high-risk group, the low-risk group experienced significantly longer overall survival [hazard ratio (HR) 2.887, P < 0.001] as well as relapse-free survival (HR 1.482, P = 0.01). CONCLUSIONS: The cancer cachexia risk score constructed and validated demonstrated good performance in identifying those digestive tract cancer patients before abdominal surgery at a higher risk of cancer cachexia and unfavourable survival. This risk score can help clinicians to enhance their capabilities to screen for cancer cachexia, assess patient prognosis, and strengthen early decision-making on targeted approaches to attune cancer cachexia for digestive tract cancer patients before abdominal surgery.

Identification of Key Diagnostic Markers and Immune Infiltration in Osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a worldwide chronic disease of the articulating joints. An increasing body of data demonstrates the immune system's involvement in osteoarthritis. The molecular mechanisms of OA are still unclear. This study aimed to search for OA immunerelated hub genes and determine appropriate diagnostic markers to help the detection and treatment of the disease. METHODS: Gene expression data were downloaded from the GEO database. Firstly, we analyzed and identified the differentially expressed genes (DEGs) using R packages. Meanwhile, ssGSEA was used to determine the activation degree of immune-related genes (IRGs), and WGCNA analysis was applied to search for co-expressed gene modules associated with immune cells. Then, critical networks and hub genes were found in the PPI network. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway enrichment analyzed the biological functions of genes. The ability of the hub genes to differentiate OA from controls was assessed by the area under the ROC curve. A miRNA and transcription factor (TF) regulatory network was constructed according to their relationship with hub genes. Finally, the validation of hub genes was carried out by qPCR. RESULTS: In total, 353 DEGs were identified in OA patients compared with controls, including 222 upregulated and 131 downregulated genes. WGCNA successfully identified 34 main functional modules involved in the pathogenesis of OA. The most crucial functional module involved in OA included 89 genes. 19 immune-related genes were obtained by overlapping DEGs with the darkgrey module. The String database was constructed using the protein-protein interaction (PPI) network of 19 target genes, and 7 hub genes were identified by MCODE. ROC curve showed that 7 hub genes were potential biomarkers of OA. The expression levels of hub genes were validated by qPCR, and the results were consistent with those from bioinformatic analyses. CONCLUSION: Immune-related hub genes, including TYROBP, ITGAM, ITGB2, C1QC, MARCO, C1QB, and TLR8, may play critical roles in OA development. ITGAM had the highest correction on immune cells.

Loss of body weight and skeletal muscle negatively affect postoperative outcomes after major abdominal surgery in geriatric patients with cancer.

OBJECTIVES: Malnutrition characterized by the involuntary loss of body weight and skeletal muscle can be the result of both aging and malignancy. As a result, geriatric patients could face an increased nutritional risk. This study aimed to investigate the nutritional and functional status of geriatric patients and their association with postoperative complications. METHODS: Patients who underwent abdominal surgery for digestive cancer in our center between January 2020 and August 2021 were included in the study. Computed tomography scans were collected to evaluate muscle mass and density. Changes in body weight, muscle strength, physical performances, nutritional risk, and status were evaluated upon admission. Postoperative outcomes collected included postoperative length of stay, complications, and 30-d readmission. RESULTS: A total of 1513 patients were included for the analysis. Of these, 72.8% were at risk for malnutrition (70.3% in the non-geriatric group and 75.4% in the geriatric group; P = 0.031), and 28.9% had malnutrition according to the Subjective Global Assessment (26.0% in the non-geriatric group and 31.8% in the geriatric group; P = 0.016). Compared with younger patients, geriatric patients have decreased muscle mass (skeletal muscle index, 44.8 versus 47.4; P < 0.001) and skeletal muscle density. Significant weight loss and loss of skeletal muscle occurred concurrently in 18.8% of the patients and were more frequent in the geriatric group (22.3% versus 14.7%; P < 0.001). In multivariate analysis, an age of 65 y or older (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.07-1.86; P = 0.014), a serum albumin level ≤4.11 g/dL (OR, 1.35; 95% CI, 1.03-1.77; P = 0.03), skeletal muscle loss (OR, 1.69; 95% CI, 1.28-2.24; P < 0.001), declined functional status (OR, 1.5; 95% CI, 1.14-1.98; P = 0.004), systematic inflammation (OR, 1.71; 95% CI, 1.09-2.8; P = 0.026), and significant weight loss (OR, 1.4; 95% CI, 1.06-2.85; P = 0.017) were independent predictors of overall postoperative complications. Although there was a trend of interactions between advanced age, skeletal muscle loss, and significant weight loss, multivariate analysis showed none of the interactions were significantly predictive of overall postoperative complications. CONCLUSIONS: Geriatric patients are at greater risk for malnutrition. Their declined nutritional and functional status together with advanced age could increase the risk for postoperative complications. Nutrition evaluation should be part of the preoperative workup, and timely interventions should be initiated if needed, especially in geriatric patients.

Highly efficient self-floating jellyfish-like solar steam generators based on the partially carbonized Enteromorpha aerogel.

Solar steam generation (SSG) is a very promising desalination technology. However, new photothermal materials are still to be explored to further reduce the cost, and the device structure is still to be innovated to improve the structural integrality and evaporation performance. In this work, an all-in-one highly-efficient and self-floating jellyfish-like SSG (SFJ-SSG) is developed based on partially carbonized Enteromorpha (EA) aerogel (PCEAA). The carbonized top surface exhibits high solar absorption ability and excellent photothermal effect, while the uncarbonized EA retains the hydrophilicity and high-water transport capability due to the nature of tubular algal plant. Moreover, the heat produced by photothermal effect of the carbonized EA is confined at the top surface due to the thermal insulation of the uncarbonized layer, which is very beneficial for interfacial water evaporation. After optimizing the carbonization time and the height of the SFJ-SSG, a high evaporation rate of 1.87 kg m-2h-1 is obtained under 1.0 sun irradiation, which outcompetes most SSG based on carbonized biomass. The development of SFJ-SSG based on EA not only minimizes the cost of SSG, but also solves the EA pollution, ensuring the broad prospect in practical applications.

Effect of electroacupuncture for Pisa syndrome in Parkinson's disease: A case report.

BACKGROUND: Pisa syndrome (PS) refers to marked lateral flexion of the trunk with a Cobb angle greater than 10°, which is typically mobile and can be resolved by lying down. PS is one of the most common postural deformities secondary to Parkinson's disease (PD) and can aggravate scoliosis in the advanced stages of PD. CASE SUMMARY: Here, we present the case of a 53-year-old woman who presented with lateral curvature for 6 mo. Full spine X-ray films in the correct position showed that the thoracolumbar spine was bent to the right without any rotation of the vertebrae. The patient was diagnosed with Pisa syndrome. After receiving a month's treatment with electroacupuncture, the Cobb angle decreased from 18.14° to 13.41°. CONCLUSION: This case demonstrates that electroacupuncture can effectively improve Pisa syndrome secondary to PD with few side effects and a low risk of recurrence. Additionally, early accurate diagnosis and timely intervention are meaningful for the prognosis of PS.

Single-cell RNA sequence presents atlas analysis for chondrocytes in the talus and reveals the potential mechanism in coping with mechanical stress.

Chondrocytes are indispensable for the function of cartilage because they provide the extracellular matrix. Therefore, gaining insight into the chondrocytes may be helpful in understanding cartilage function and pinpointing potential therapeutical targets for diseases. The talus is a part of the ankle joint, which serves as the major large joint that bears body weight. Compared with the distal tibial and fibula, the talus bears much more mechanical loading, which is a risk factor for osteoarthritis (OA). However, in most individuals, OA seems to be absent in the ankle, and the cartilage of the talus seems to function normally. This study applied single-cell RNA sequencing to demonstrate atlas for chondrocyte subsets in healthy talus cartilage obtained from five volunteers, and chondrocyte subsets were annotated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for each cell type, cell-cell interactions, and single-cell regulatory network inference and clustering for each cell type were conducted, and hub genes for each cell type were identified. Immunohistochemical staining was used to confirm the presence and distribution of each cell type. Two new chondrocyte subsets were annotated as MirCs and SpCs. The identified and speculated novel microenvironment may pose different directions in chondrocyte composition, development, and metabolism in the talus.

Strain-boosted hyperoxic graphene oxide efficiently loading and improving performances of microcystinase.

Harmful Microcystis blooms (HMBs) and microcystins (MCs) that are produced by Microcystis seriously threaten water ecosystems and human health. This study demonstrates an eco-friendly strategy for simultaneous removal of MCs and HMBs by adopting unique hyperoxic graphene oxides (HGOs) as carrier and pure microcystinase A (PMlrA) as connecting bridge to form stable HGOs@MlrA composite. After oxidation, HGOs yield inherent structural strain effects for boosting the immobilization of MlrA by material characterization and density functional theory calculations. HGO5 exhibits higher loading capacities for crude MlrA (1,559 mg·g-1) and pure MlrA (1,659 mg·g-1). Moreover, the performances of HGO5@MlrA composite, including the capability of removing MCs and HMBs, the ecological and human safety compared to MlrA or HGO5 treatment alone, have been studied. These results indicate that HGO5 can be used as a promising candidate material to effectively improve the application potential of MlrA in the simultaneous removal of MCs and HMBs.

Validation of GLIM malnutrition criteria in cancer patients undergoing major abdominal surgery: A large-scale prospective study.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) is a new framework to evaluate nutritional status. It has been validated mostly by retrospective studies, which often failed to follow the framework as recommended due to their retrospective nature. This study aims to validate GLIM with a large prospective study and investigate its role in predicting short-term surgical outcomes. METHODS: Patients who underwent abdominal surgery for digestive cancer in our center were prospectively included between January 2020 and December 2020. Data collected included demographic information, clinical and pathological information, lab results, and computed tomography scans. Muscle strength, physical performances, quality of life and cancer symptom burden were evaluated upon admission. Multiple tools for nutritional risk screening were used. Nutritional status was evaluated with Subjective Global Assessment (SGA) and GLIM. Postoperative outcomes collected included return of gastrointestinal function, postoperative length of stay, complications, 30-day readmission and 30-day mortality. RESULTS: A total of 1115 patients were evaluated with GLIM criteria. Inter-rater reliability was good [k = 0.76, 95% confidence interval (CI): 0.72-0.80]. The accuracy of GLIM diagnosis compared to the semi-gold standard SGA varied with the screening method used. GLIM with MNA-SF screening [area under the curve (AUC): 0.78] and GLIM without screening (AUC: 0.77) were the two most accurate protocols, and there was no significant difference between the two from a clinical perspective. GLIM can predict preoperative nutritional status, functional status, symptom burden and quality of life. It can also predict complications after surgery [odds ratio (OR) = 2.31, 95% CI: 1.67-3.21], especially infection related complications (OR = 2.19, 95% CI: 1.38-3.49) and wound healing related complications (OR = 2.54, 95% CI: 1.38-4.71). CONCLUSIONS: GLIM malnutrition criteria showed good inner-rater reliability and moderate agreement with SGA. GLIM can be used to predict preoperative nutritional status, functional status, cancer related symptoms, and quality of life. It can also predict postoperative outcomes especially complications that are related to infection and wound healing. In surgical candidates, the screening process could potentially be skipped so that GLIM assessment can be faster, more accessible, and more sensitive.

Single Cell Mass Spectrometry With a Robotic Micromanipulation System for Cell Metabolite Analysis.

OBJECTIVE: The increasing demand for unraveling cellular heterogeneity has boosted single cell metabolomics studies. However, current analytical methods are usually labor-intensive and hampered by lack of accuracy and efficiency. METHODS: we developed a first-ever automated single cell mass spectrometry system (named SCMS) that facilitated the metabolic profiling of single cells. In particular, extremely small droplets of sub nano-liter were generated to extract the single cells, and the underlying mechanism was verified theoretically and experimentally. This was crucial to minimize the dilution of the trace cellular contents and enhance the analytical sensitivity. Based on the precise 3D positioning of the pipette tip, we established a visual servoing robotic micromanipulation platform on which single cells were sequentially extracted, aspirated, and ionized, followed by the mass spectrometry analyses. RESULTS: With the SCMS system, inter-operator variability was eliminated and working efficiency was improved. The performance of the SCMS system was validated by the experiments on bladder cancer cells. MS and MS2 analyses of single cells enable us to identify several cellular metabolites and the underlying inter-cell heterogeneity. CONCLUSION: In contrast to traditional methods, the SCMS system functions without human intervention and realizes a robust single cell metabolic analysis. SIGNIFICANCE: the SCMS system upgrades the way how single cell metabolites were analyzed, and has the potential to be a powerful tool for single cell metabolomics studies.

Electro-acupuncture on Vascular Parkinsonism with multiple sleep disorders: A Case Report.

Vascular Parkinsonism (VP) is a kind of rare secondary Parkinsonism caused by vascular lesions. Patients with VP experience not only movement disorders but also sleep disorders. But treatment options are limited and often associated with undesirable adverse effects. Electro-acupuncture (EA) is a safe, rapid work, easy operation, and convenient complementary replacement therapy. We report a case of a 51-year-old man who presented with VP and multiple sleep disorders. Based on clinical evaluation and nocturnal hospital-based polysomnography (PSG), the patient had severe PLMD (PSG showed severe periodic leg movements), excessive daytime sleepiness (EDS, the score of the ESS is 16), and probable rapid eye movement sleep disorder (RBD). Parkinson's disease sleep scale (PDSS) score, Pittsburgh sleep quality index (PSQI), and periodic leg movements index were 93, 11, and 135.2, respectively. After 8 weeks of EA treatment, the patient reported that the symptoms of subjective and objective sleep disturbance were significantly alleviated without any discomfort. This case report may provide a new alternative and complementary therapy for VP patients with sleep disturbance but more definitive and robust evidence is needed to support its efficacy.

Moderate Mechanical Stimulation Protects Rats against Osteoarthritis through the Regulation of TRAIL via the NF-κB/NLRP3 Pathway.

The aim of this study was to examine exercise-related genes in articular cartilage identified through bioinformatics analysis to dissect the potential signaling pathway involved in mechanical stimulation in osteoarthritis (OA). To this end, we evaluated the GSE74898 dataset from the Gene Expression Omnibus database for exercise-related differentially expressed miRNAs (DE-miRNAs) using the R software package and predicted potential target genes for these miRNAs using miRTarBase. Functional annotation and pathway enrichment analysis were performed for these potential DE-miRNA targets. The effects of mechanical stimulation on the tumor necrosis factor-related apoptosis-induced ligand (TRAIL)/nuclear factor-kappa B (NF-κB)/nucleotide-binding and oligomerization domain-like receptor containing protein 3 (NLRP3) signaling pathway were evaluated in articular cartilage and chondrocytes. A total of 394 DE-miRNAs were identified (103 upregulated miRNAs; 291 downregulated miRNAs) in the cartilage of rats following treadmill exercise compared to the cartilage of unexercised control rats. Thus, mechanical stimulation could modulate the TRAIL/NF-κB/NLRP3 signaling pathway on OA. Histological and protein analysis demonstrated that moderate-intensity treadmill exercise could ameliorate OA through the downregulation of TRAIL. Furthermore, moderate cyclic tensile strain (CTS) could rescue chondrocytes from the effects of TRAIL via the inhibition of the nuclear translocation of NF-κB p65 and formation of NLRP3. Our findings indicate that moderate mechanical stimulation could ameliorate the degeneration of cartilage and chondrocyte damage through the inhibition of the TRAIL/NF-κB/NLRP3 pathway.

Simultaneous Microcystin Degradation and Microcystis aeruginosa Inhibition with the Single Enzyme Microcystinase A.

Harmful Microcystis blooms (HMBs) seriously threaten the ecology of environments and human health. Microcystins (MCs) produced by Microcystis are powerful mediators of HMB induction and maintenance. In this study, microcystinase A (MlrA), an enzyme with MC-degrading ability, was successfully obtained at over 90% purity for the first time through overexpression in Escherichia coli K12 TB1. The obtained MlrA exhibited high stability at high temperature and under alkaline conditions, while also exhibiting a long half-life. MlrA selectively inhibited MC-producing Microcystis cultures, but had no effect on MC-nonproducing Synechocystis cultures. The inhibition mechanism of MlrA against Microcystis was investigated by evaluating the morphological and physiological characteristics of cultures. MlrA effectively degraded extracellular MCs and decreased the synthesis of intracellular MCs by causing downregulation of genes involved in the microcystin biosynthesis pathway. Concomitantly, MlrA inhibited Microcystis photosynthesis by causing the downregulated expression of important photosynthesis pathway genes and interrupting electron transport chain activities and pigment synthesis. Thus, MlrA achieved the inhibition of Microcystis growth by reducing its photosynthetic capacity and intracellular MC contents, while also degrading extracellular MCs. On the basis of these results, we propose a new paradigm to achieve the simultaneous removal of MCs and HMBs using the single enzyme characterized here.