Exploring the use of deep learning models for accurate tracking of 3D zebrafish trajectories.

Zebrafish are ideal model organisms for various fields of biological research, including genetics, neural transmission patterns, disease and drug testing, and heart disease studies, because of their unique ability to regenerate cardiac muscle. Tracking zebrafish trajectories is essential for understanding their behavior, physiological states, and disease associations. While 2D tracking methods are limited, 3D tracking provides more accurate descriptions of their movements, leading to a comprehensive understanding of their behavior. In this study, we used deep learning models to track the 3D movements of zebrafish. Videos were captured by two custom-made cameras, and 21,360 images were labeled for the dataset. The YOLOv7 model was trained using hyperparameter tuning, with the top- and side-view camera models trained using the v7x.pt and v7.pt weights, respectively, over 300 iterations with 10,680 data points each. The models achieved impressive results, with an accuracy of 98.7% and a recall of 98.1% based on the test set. The collected data were also used to generate dynamic 3D trajectories. Based on a test set with 3,632 3D coordinates, the final model detected 173.11% more coordinates than the initial model. Compared to the ground truth, the maximum and minimum errors decreased by 97.39% and 86.36%, respectively, and the average error decreased by 90.5%.This study presents a feasible 3D tracking method for zebrafish trajectories. The results can be used for further analysis of movement-related behavioral data, contributing to experimental research utilizing zebrafish.

Efficacy and safety of telitacicept, a BLyS/APRIL dual inhibitor, in the treatment of IgA nephropathy: a retrospective case-control study.

Background: Telitacicept, a B lymphocyte stimulator/A proliferation-inducing ligand dual-target fusion protein, has recently been used in autoimmune diseases. We assessed the efficacy and safety of telitacicept in immunoglobulin A nephropathy (IgAN) patients. Methods: This study included 42 IgAN patients who received telitacicept treatment, forming the 'whole telitacicept group'. Among them, 20 patients who had not previously received corticosteroid (CS) therapy or immunosuppressive (IS) agents were categorized as the 'newly treated telitacicept subgroup'. Additionally, 28 patients who were selected to match historical controls received conventional IS therapy (CS therapy with/without IS agents) and were classified as the 'conventional IS group'. Telitacicept was partially used in combination with conventional IS therapy, including initial CS in different doses. Various indicators were compared at 4-week intervals up to 24 weeks among the three groups. Results: After 24 weeks of treatment, the 24-hour proteinuria decreased from 1.70 g [interquartile range (IQR) 1.05-2.58] to 0.21 g (IQR 0.39-0.13) (P = .043) in the newly treated telitacicept subgroup, from 1.78 g (IQR 0.97-2.82) to 0.44 g (IQR 1.48-0.16) (P = .001) in the conventional IS group and from 1.07 g (IQR 0.66-1.99) to 0.26 g (IQR 0.59-0.17) (P = .028) in the whole telitacicept group. The estimated glomerular filtration rate (eGFR) increased from 76.58 ± 30.26 ml/min/1.73 m2 to 80.30 ± 26.76 ml/min/1.73 m2 (P = .016) in the newly treated telitacicept subgroup, from 72.73 ± 33.41 ml/min/1.73 m2 to 84.08 ± 26.81 ml/min/1.73 m2 (P = .011) in the conventional IS group and from 70.10 ± 32.88 ml/min/1.73 m2 to 71.21 ± 31.49 ml/min/1.73 m2 (P = .065) in the whole telitacicept group. During follow-up periods, the efficacy rates of the three groups did not show statistically significant differences and no serious adverse events were observed. Conclusions: Telitacicept may be a safe and effective treatment for IgAN, offering reductions in proteinuria and increases in eGFR similar to conventional IS therapy. After a 24-week follow-up, the incidence of adverse events was lower for telitacicept than for conventional IS therapy.

Brain Iron in signature regions relating to cognitive aging in older adults: the Taizhou Imaging Study.

BACKGROUND: Recent magnetic resonance imaging (MRI) studies have established that brain iron accumulation might accelerate cognitive decline in Alzheimer's disease (AD) patients. Both normal aging and AD are associated with cerebral atrophy in specific regions. However, no studies have investigated aging- and AD-selective iron deposition-related cognitive changes during normal aging. Here, we applied quantitative susceptibility mapping (QSM) to detect iron levels in cortical signature regions and assessed the relationships among iron, atrophy, and cognitive changes in older adults. METHODS: In this Taizhou Imaging Study, 770 older adults (mean age 62.0 ± 4.93 years, 57.5% women) underwent brain MRI to measure brain iron and atrophy, of whom 219 underwent neuropsychological tests nearly every 12 months for up to a mean follow-up of 2.68 years. Global cognition was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Domain-specific cognitive scores were obtained from MoCA subscore components. Regional analyses were performed for cortical regions and 2 signature regions where atrophy affected by aging and AD only: Aging (AG) -specific and AD signature meta-ROIs. The QSM and cortical morphometry means of the above ROIs were also computed. RESULTS: Significant associations were found between QSM levels and cognitive scores. In particular, after adjusting for cortical thickness of regions of interest (ROIs), participants in the upper tertile of the cortical and AG-specific signature QSM exhibited worse ZMMSE than did those in the lower tertile [ ß = -0.104, p = 0.026; ß = -0.118, p = 0.021, respectively]. Longitudinal analysis suggested that QSM values in all ROIs might predict decline in ZMoCA and key domains such as attention and visuospatial function (all p < 0.05). Furthermore, iron levels were negatively correlated with classic MRI markers of cortical atrophy (cortical thickness, gray matter volume, and local gyrification index) in total, AG-specific signature and AD signature regions (all p < 0.05). CONCLUSION: AG- and AD-selective iron deposition was associated with atrophy and cognitive decline in elderly people, highlighting its potential as a neuroimaging marker for cognitive aging.

Quantum Equation-of-Motion Method with Single, Double, and Triple Excitations.

The quantum equation-of-motion (qEOM) method with single and double excitations (qEOM-SD) has been proposed to study electronically excited states, but it fails to handle states dominated by double excitations. In this work, we reformulate the qEOM method within the effective Hamiltonian framework that satisfies the killer condition, and then present an efficient implementation incorporating single, double, and triple excitations. To reduce computational complexity, we employ point-group symmetry and perturbation theory to screen triple excitations, effectively reducing the scaling from No6Nv6 to No5Nv5, where No and Nv are the numbers of occupied and virtual spin orbitals, respectively. Furthermore, we account for the effect of neglected triple excitations by introducing a perturbative correction to the excitation energy. We apply this method to challenging cases where the qEOM-SD method exhibits significant errors, such as the 2 1Δ state of CH+ and the 2 1Σ state of HF. Our new method achieves energy errors below 0.18 eV while incorporating less than 8.2% of triple excitations. Additionally, we extend the operator screening technique to the quantum subspace expansion method for the efficient inclusion of selected triple excitations.

The joint effect of cumulative metabolic parameters on the risk of type 2 diabetes: a population-based cohort study.

BACKGROUND AND AIMS: This study aimed to examine the cumulative effects of body mass index (BMI), body roundness index (BRI), pulse pressure (PP), triglycerides (TG), high-density lipoprotein cholesterol (HDL) and fasting plasma glucose (FPG) on Type 2 diabetes (T2D) morbidity. METHODS: A total of 78,456 participants aged older than 45 years were extracted from basic public health services in China. During the 2-year follow-up, 6,942 individuals had developed T2D. The binary logistic regression models and multinomial logistic regression models were conducted to investigate the effects of cumulative metabolic parameters on incident T2D, prediabetes regression and progression. RESULTS: We found statistically deleterious impacts of exposure to high cumulative BMI, BRI, PP, TG and low cumulative HDL on T2D morbidity and prediabetes progression. Compared to the group with low cumulative of all five parameters, the adjusted ORs for new-onset T2D for participants presenting with 1-2, 3, and 4-5 elevated metabolic parameters were 1.41(1.31,1.52), 1.93(1.74,2.13) and 2.21(1.94,2.51), respectively. There was additive interaction between FPG level and cumulative metabolic parameters with T2D. Compared with participants with the lowest quartile of FPG and low cumulative of all 5 parameters, those with the highest quartile of FPG and high cumulative of 4-5 parameters had a 14.63 [95% CI (12.27, 17.42)] higher risk of incident T2D. CONCLUSIONS: Participants with more numbers of high-cumulative metabolic parameters were associated with a higher risk of incident T2D and prediabetes progression. A high level of normal FPG could enhance these risks.

Potential of Dental Pulp Stem Cell Exosomes: Unveiling miRNA-Driven Regenerative Mechanisms.

Human dental pulp stem cells (hDPSCs) have emerged as a promising resource in regenerative medicine due to their unique ability to secrete exosomes containing a diverse array of bioactive molecules, particularly microRNAs (miRNAs). These exosomes appear to be essential for stimulating regenerative mechanisms, especially those associated with stem cell pluripotency and tissue repair. However, several challenges such as cargo specificity and delivery efficiency need to be addressed to maximise the therapeutic potential of hDPSC-derived exosomes and miRNA-based therapies. This narrative review explores hDPSCs' potential in regenerative medicine by examining their role in tissue engineering, secretome composition, exosome function, exosomal miRNA in diverse models, and miRNA profiling. Therefore, it is imperative to sustain ongoing research on miRNA to advance clinical applications in the field of regenerative medicine and dentistry. A comprehensive understanding of the specific miRNA composition within hDPSC-derived exosomes is essential to elucidate their mechanistic roles in diverse disease states and to inform the development of innovative therapeutic strategies. These findings hold significant potential for the development of innovative regenerative therapies and emphasises the importance of establishing a strong connection between translational research discoveries and clinical applications. hDPSC-derived exosomes and miRNA-based therapies play a crucial role in immune modulation, regenerative dentistry, and tissue repair.

The transformative potential of mRNA vaccines for glioblastoma and human cancer: technological advances and translation to clinical trials.

Originally devised for cancer control, mRNA vaccines have risen to the forefront of medicine as effective instruments for control of infectious disease, notably their pivotal role in combating the COVID-19 pandemic. This review focuses on fundamental aspects of the development of mRNA vaccines, e.g., tumor antigens, vector design, and precise delivery methodologies, - highlighting key technological advances. The recent, promising success of personalized mRNA vaccines against pancreatic cancer and melanoma illustrates the potential value for other intractable, immunologically resistant, solid tumors, such as glioblastoma, as well as the potential for synergies with a combinatorial, immunotherapeutic approach. The impact and progress in human cancer, including pancreatic cancer, head and neck cancer, bladder cancer are reviewed, as are lessons learned from first-in-human CAR-T cell, DNA and dendritic cell vaccines targeting glioblastoma. Going forward, a roadmap is provided for the transformative potential of mRNA vaccines to advance cancer immunotherapy, with a particular focus on the opportunities and challenges of glioblastoma. The current landscape of glioblastoma immunotherapy and gene therapy is reviewed with an eye to combinatorial approaches harnessing RNA science. Preliminary preclinical and clinical data supports the concept that mRNA vaccines could be a viable, novel approach to prolong survival in patients with glioblastoma.

Evaluating anchorage and torque control in adolescent patients with Class II Division 1 malocclusion among 3 appliances.

INTRODUCTION: The objective of this study was to compare the differences in anchorage and torque control among the Tweed edgewise, Roth, and physiological anchorage Spee-wire systems (PASS) appliances (Zhejiang Xinya Technology Co, Ltd, Hangzhou, China). METHODS: A sample of 90 adolescent patients with Angle Class II Division 1 malocclusion (30 Tweed edgewise appliances, 30 Roth appliances, and 30 PASS appliances) with maximum anchorage requirements in the maxilla were collected for this study. The pretreatment baseline levels of the 3 groups were compared initially, and then the differences between the 3 appliances in anchorage and torque control were analyzed after superimposing the pretreatment and posttreatment lateral cephalograms and maxillary 3-dimensional (3D) digital models, respectively. RESULTS: There was no statistical difference in the pretreatment baseline levels of 3 groups, including gender, age, sagittal skeletal types (ANB), vertical skeletal types (SN-GoGn), anchorage requirements, and occlusal plane inclination (SN-OP). After superimposing the pretreatment and posttreatment lateral cephalograms and 3D digital models, respectively, no statistical differences were observed between the measurement results obtained from lateral cephalograms and 3D digital models. Among the measurement variables assessed in this study, statistical differences were observed in the mesial displacement of maxillary first molars, the incisor retraction, and the torque variation of maxillary central incisors among the 3 groups. Specifically, the Tweed group exhibited lower mesial displacement of maxillary first molars compared with the PASS and Roth groups. Furthermore, the Tweed group exhibited the greatest amount of incisor retraction and torque variation of maxillary central incisors, followed by the Roth group and then the PASS group. The remaining measurement variables for the 3 groups showed no statistical differences, including vertical variation of maxillary first molars and central incisors, torque variation of maxillary first molars and canines, mesiodistal inclination variation of maxillary first molars and canines, width variation between maxillary first molars, and width variation between maxillary canines. CONCLUSIONS: Compared with contemporary preadjusted straight wire appliances, the Tweed edgewise appliance has superiority in molar anchorage control. In contrast, compared with the Roth appliances, the PASS appliances without any auxiliary anchorage devices could make full use of physiological anchorage to achieve adequate control of molar anchorage. Clinical orthodontists may need to pay extra attention to physiological anchorage. The difference in torque control varies depending on the respective characteristics of bracket designs.

An iron-rich subset of macrophages promotes tumor growth through a Bach1-Ednrb axis.

We define a subset of macrophages in the tumor microenvironment characterized by high intracellular iron and enrichment of heme and iron metabolism genes. These iron-rich tumor-associated macrophages (iTAMs) supported angiogenesis and immunosuppression in the tumor microenvironment and were conserved between mice and humans. iTAMs comprise two additional subsets based on gene expression profile and location-perivascular (pviTAM) and stromal (stiTAM). We identified the endothelin receptor type B (Ednrb) as a specific marker of iTAMs and found myeloid-specific deletion of Ednrb to reduce tumor growth and vascular density. Further studies identified the transcription factor Bach1 as a repressor of the iTAM transcriptional program, including Ednrb expression. Heme is a known inhibitor of Bach1, and, correspondingly, heme exposure induced Ednrb and iTAM signature genes in macrophages. Thus, iTAMs are a distinct macrophage subset regulated by the transcription factor Bach1 and characterized by Ednrb-mediated immunosuppressive and angiogenic functions.

Irregularity of visual motion perception and negative symptoms in schizophrenia.

Schizophrenia (SZ) is a severe psychiatric disorder characterized by perceptual, emotional, and behavioral abnormalities, with cognitive impairment being a prominent feature of the disorder. Recent studies demonstrate irregularity in SZ with increased variability on the neural level. Is there also irregularity on the psychophysics level like in visual perception? Here, we introduce a methodology to analyze the irregularity in a trial-by-trial way to compare the SZ and healthy control (HC) subjects. In addition, we use an unsupervised clustering algorithm K-means + + to identify SZ subgroups in the sample, followed by validation of the subgroups based on intraindividual visual perception variability and clinical symptomatology. The K-means + + method divided SZ patients into two subgroups by measuring durations across trials in the motion discrimination task, i.e., high, and low irregularity of SZ patients (HSZ, LSZ). We found that HSZ and LSZ subgroups are associated with more negative and positive symptoms respectively. Applying a mediation model in the HSZ subgroup, the enhanced irregularity mediates the relationship between visual perception and negative symptoms. Together, we demonstrate increased irregularity in visual perception of a HSZ subgroup, including its association with negative symptoms. This may serve as a promising marker for identifying and distinguishing SZ subgroups.

Next-Generation swimming pool drowning prevention strategy integrating AI and IoT technologies.

Drowning, as a leading cause of unintentional injury-related deaths worldwide, is a major public health concern. Swimming pool drowning is the main cause of most drowning incidents, and even with preventive measures such as surveillance cameras and lifeguards, tens of thousands of lives are lost to drowning every year. To address this issue, technology is being utilized to prevent drowning accidents and provide timely alerts for rescue. This paper explores the use of drowning prevention technology in embedded systems within enclosed environments, artificial intelligence (AI), and the Internet of Things (IoT) to decrease the likelihood of drowning incidents. Embedded systems play a critical role in such technology, enabling real-time monitoring, identification of dangerous situations, and prompt alerting. Due to their ease of installation and technical implementation, embedded devices are especially effective as drowning prevention devices. The image recognition capabilities of drowning prevention systems are enhanced through computer vision. Swimming pool drowning situations can be identified with the help of cameras and deep learning technologies, thereby increasing rescue efficiency. Finally, the IoT endows drowning prevention systems with comprehensive intelligence by connecting various devices and communication tools. Real-time alert transmission and analysis have become possible, enabling the early prediction of dangerous situations and the implementation of preventive measures, significantly reducing drowning incidents. In summary, the integration of these three types of drowning prevention technologies represents significant progress. The flexibility, accuracy, and intelligence of drowning prevention systems are enhanced through the incorporation of these technologies, providing robust support for safeguarding human lives and thus potentially saving tens of thousands of lives each year.

Multimodal registration network with multi-scale feature-crossing.

PURPOSE: A critical piece of information for prostate intervention and cancer treatment is provided by the complementary medical imaging modalities of ultrasound (US) and magnetic resonance imaging (MRI). Therefore, MRI-US image fusion is often required during prostate examination to provide contrast-enhanced TRUS, in which image registration is a key step in multimodal image fusion. METHODS: We propose a novel multi-scale feature-crossing network for the prostate MRI-US image registration task. We designed a feature-crossing module to enhance information flow in the hidden layer by integrating intermediate features between adjacent scales. Additionally, an attention block utilizing three-dimensional convolution interacts information between channels, improving the correlation between different modal features. We used 100 cases randomly selected from The Cancer Imaging Archive (TCIA) for our experiments. A fivefold cross-validation method was applied, dividing the dataset into five subsets. Four subsets were used for training, and one for testing, repeating this process five times to ensure each subset served as the test set once. RESULTS: We test and evaluate our technique using fivefold cross-validation. The cross-validation trials result in a median target registration error of 2.20 mm on landmark centroids and a median Dice of 0.87 on prostate glands, both of which were better than the baseline model. In addition, the standard deviation of the dice similarity coefficient is 0.06, which suggests that the model is stable. CONCLUSION: We propose a novel multi-scale feature-crossing network for the prostate MRI-US image registration task. A random selection of 100 cases from The Cancer Imaging Archive (TCIA) was used to test and evaluate our approach using fivefold cross-validation. The experimental results showed that our method improves the registration accuracy. After registration, MRI and TURS images were more similar in structure and morphology, and the location and morphology of cancer were more accurately reflected in the images.

A causal relationship between sarcopenia and cognitive impairment: A Mendelian randomization study.

OBJECTIVE: Sarcopenia and cognitive impairment often coexist in the elderly. In this study, we investigated the causal relationship between sarcopenia-related muscle characteristics and cognitive performance. METHODS: We used linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR) analyses to estimate genetic correlations and causal relationships between genetically predicted sarcopenia-related muscle traits and cognitive function, as well as cognitive function-based discovery samples and replicated samples. Estimated effect sizes were derived from a fixed-effects meta-analysis. RESULTS: Our univariate genome-wide association study (GWAS) meta-analysis indicated a causal relationship between appendicular lean mass (ALM) (ß = 0.049; 95% confidence interval (CI): 0.032-0.066, P < 0.001) and walking pace (ß = 0.349; 95% CI: 0.210-0.487, P < 0.001) with cognitive function, where a causal relationship existed between ALM in both male and female (ßALM-Male(M) = 0.060; 95% CI: 0.031-0.089, PALM-M < 0.001; ßALM-Female(F) = 0.045; 95% CI: 0.020-0.069, PALM-F < 0.001) with cognitive function. Low grip strength was not causally associated with cognitive function (ß = -0.045; 95% CI: -0.092 - -0.002, P = 0.062). A reverse causality GWAS meta-analysis showed a causal relationship between cognitive function and ALM (ß = 0.033; 95% CI: 0.018-0.048, P < 0.001) and walking pace (ß = 0.039; 95% CI: 0.033-0.051, P < 0.001), where ALM in both male and female showed a causality (ßALM-M = 0.041; 95% CI: 0.019-0.063, PALM-M < 0.001; ßALM-F = 0.034; 95% CI: 0.010-0.058, PALM-F = 0.005). Cognitive function was not causally related to low grip strength (ß = -0.024; 95% CI: -0.073-0.025, P = 0.344). Multivariable MR1 (MVMR1) analyses showed a significant causal relationship for ALM (ß = 0.077; 95% CI: 0.044-0.109, P = 0.000) and walking pace (ß = 0.579; 95% CI: 0.383-0.775, P = 0.000) and cognitive function. Multivariable MR2 (MVMR2) multivariate analysis showed that ALM causality remained (ß = 0.069; 95% CI: 0.033-0.106, P = 0.000), and walking pace (ß = 0.589; 95% CI: 0.372-0.806, P = 0.000). CONCLUSIONS: Bidirectional two-sample MR demonstrated that sarcopenia-related muscle characteristics and cognitive performance were positive causal genetic risk factors for each other, while a multivariable MR study demonstrated that low ALM and a slow walking pace were causally involved in reduced cognitive performance. This study suggests a causal relationship between sarcopenia and cognitive impairment in older adults and provide new ideas for prevention and treatment.

Homologous mapping yielded a comprehensive predicted protein-protein interaction network for peanut (Arachis hypogaea L.).

BACKGROUND: Protein-protein interactions are the primary means through which proteins carry out their functions. These interactions thus have crucial roles in life activities. The wide availability of fully sequenced animal and plant genomes has facilitated establishment of relatively complete global protein interaction networks for some model species. The genomes of cultivated and wild peanut (Arachis hypogaea L.) have also been sequenced, but the functions of most of the encoded proteins remain unclear. RESULTS: We here used homologous mapping of validated protein interaction data from model species to generate complete peanut protein interaction networks for A. hypogaea cv. 'Tifrunner' (282,619 pairs), A. hypogaea cv. 'Shitouqi' (256,441 pairs), A. monticola (440,470 pairs), A. duranensis (136,363 pairs), and A. ipaensis (172,813 pairs). A detailed analysis was conducted for a putative disease-resistance subnetwork in the Tifrunner network to identify candidate genes and validate functional interactions. The network suggested that DX2UEH and its interacting partners may participate in peanut resistance to bacterial wilt; this was preliminarily validated with overexpression experiments in peanut. CONCLUSION: Our results provide valuable new information for future analyses of gene and protein functions and regulatory networks in peanut.

Immunomodulatory Therapy for Ischemic Heart Disease.

Ischemic heart disease is a leading cause of death worldwide, manifested clinically as myocardial infarction (and ischemic cardiomyopathy. Presently, there exists a notable scarcity of efficient interventions to restore cardiac function after myocardial infarction. Cumulative evidence suggests that impaired tissue immunity within the ischemic microenvironment aggravates cardiac dysfunction, contributing to progressive heart failure. Recent research breakthroughs propose immunotherapy as a potential approach by leveraging immune and stroma cells to recalibrate the immune microenvironment, holding significant promise for the treatment of ischemic heart disease. In this Primer, we highlight three emerging strategies for immunomodulatory therapy in managing ischemic cardiomyopathy: targeting vascular endothelial cells to rewire tissue immunity, reprogramming myeloid cells to bolster their reparative function, and utilizing adoptive T cell therapy to ameliorate fibrosis. We anticipate that immunomodulatory therapy will offer exciting opportunities for ischemic heart disease treatment.

Prevalence and risk factors of sexual dysfunction in female participants with rheumatoid arthritis: a systematic review and meta-analysis.

BACKGROUND: The prevalence and risk factors of female sexual dysfunction (FSD) in female participants with rheumatoid arthritis (RA) were reported with inconsistent results. However, no systematic review and meta-analysis of pooled data provide reliable estimates of FSD prevalence in female participants with RA. AIM: To investigate the global prevalence and risk factors of FSD in female participants with RA and to analyze the association between FSD risk and RA. METHODS: The study search of this systematic review and meta-analysis was conducted through PubMed, Cochrane Library, Web of Science, and Embase from the inception date to December 10, 2023. Random effects meta-analysis was performed to derive the pooled prevalence. Q and I2 tests were used to analyze heterogeneity among the studies. Subgroup analyses and meta-regression were used to detect the sources of heterogeneity. OUTCOMES: The pooled prevalence of FSD in female participants with RA was calculated, and odds ratios (ORs) and 95% CIs were used to assess the strength of the association between FSD-related risk factors and RA. RESULTS: A total of 13 studies were included in our analysis, involving 2327 participants. The pooled prevalence of FSD in female participants with RA was 49.1% (95% CI, 38.2%-60%). The participants with RA had a higher risk of FSD than healthy controls (OR, 3.10; 95% CI, 1.74-5.53). The significant risk factors of FSD in female participants with RA were depression status (OR, 1.42; 95% CI, 0.88-2.29) and menopause (OR, 5.46; 95% CI, 2.04-14.63). CLINICAL IMPLICATIONS: Female participants with RA had a significantly increased prevalence of FSD, indicating that sexual function in female participants with RA should be concerned by clinicians. STRENGTHS AND LIMITATIONS: The strength of this study is that it is the first meta-analysis to assess the global prevalence and risk factors of FSD in female participants with RA. A limitation is that the results, after the articles were pooled, showed significant heterogeneity and publication bias. CONCLUSIONS: The present systematic review and meta-analysis revealed that the overall prevalence of FSD in female participants with RA was 49.1%, indicating a significant association between FSD risk and RA among females. Moreover, menopause and depression status were significantly associated with FSD in female participants with RA.

Association between plasma Netrin-1 levels and motor and nonmotor symptoms in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by dopaminergic neuron degeneration and diverse motor and nonmotor symptoms. Early diagnosis and intervention are crucial but challenging due to reliance on clinical presentation. Recent research suggests potential biomarkers for early detection, including plasma netrin-1 (NTN-1), a protein implicated in neuronal survival. METHODS: This cross-sectional study recruited 105 PD patients and 65 healthy controls, assessing plasma NTN-1 levels and correlating them with clinical characteristics. Statistical analyses explored associations between NTN-1 levels and PD symptoms, considering demographic factors. RESULTS: PD patients exhibited significantly lower plasma NTN-1 levels compared to controls. NTN-1 demonstrated moderate potential as a PD biomarker. Positive correlations were found between NTN-1 levels and motor, depression, and cognitive symptoms. Multiple regression analysis revealed disease duration and NTN-1 levels as key factors influencing symptom severity. Gender also impacted symptom scores. CONCLUSION: Reduced plasma NTN-1 levels correlate with PD severity, suggesting its potential as a biomarker. However, further research is needed to elucidate the roles of NTN-1 in PD pathophysiology and validate its diagnostic and therapeutic implications. Understanding the involvement of NTN-1 may lead to personalized management strategies for PD.

Modified C-type natriuretic peptide normalizes tumor vasculature, reinvigorates antitumor immunity, and improves solid tumor therapies.

Deficit of oxygen and nutrients in the tumor microenvironment (TME) triggers abnormal angiogenesis that produces dysfunctional and leaky blood vessels, which fail to adequately perfuse tumor tissues. Resulting hypoxia, exacerbation of metabolic disturbances, and generation of an immunosuppressive TME undermine the efficacy of anticancer therapies. Use of carefully scheduled angiogenesis inhibitors has been suggested to overcome these problems and normalize the TME. Here, we propose an alternative agonist-based normalization approach using a derivative of the C-type natriuretic peptide (dCNP). Multiple gene expression signatures in tumor tissues were affected in mice treated with dCNP. In several mouse orthotopic and subcutaneous solid tumor models including colon and pancreatic adenocarcinomas, this well-tolerated agent stimulated formation of highly functional tumor blood vessels to reduce hypoxia. Administration of dCNP also inhibited stromagenesis and remodeling of the extracellular matrix and decreased tumor interstitial fluid pressure. In addition, treatment with dCNP reinvigorated the antitumor immune responses. Administration of dCNP decelerated growth of primary mouse tumors and suppressed their metastases. Moreover, inclusion of dCNP into the chemo-, radio-, or immune-therapeutic regimens increased their efficacy against solid tumors in immunocompetent mice. These results demonstrate the proof of principle for using vasculature normalizing agonists to improve therapies against solid tumors and characterize dCNP as the first in class among such agents.

A sensitive fluorescence assay of serum dipeptidyl peptidase IV activity to predict the suitability of its inhibitors in patients with type 2 diabetes mellitus.

DPP-IV inhibitors, which are close to the natural hypoglycemic pathway of human physiology and have few side effects, have been extensively employed in the management of type 2 diabetes mellitus (T2DM). However, there are currently no specific blood indicators that can indicate or predict a patient's suitability for DPP-IV inhibitors. In this study, based on the self-developed high-specificity fluorescent substrate glycyl-prolyl-N-butyl-4-amino-1, 8-naphthimide (GP-BAN), a detection method of human serum DPP-IV activity was established and optimized. The method demonstrates a favorable lower limit of detection (LOD) at 0.32 ng/mL and a satisfactory lower limit of quantification (LOQ) of 1.12 ng/mL, and can be used for the detection of DPP-IV activity in trace serum (2 µL). In addition, Vitalliptin and Sitagliptin showed similar IC50 values when human recombinant DPP-IV and human serum were used as enzyme sources, and the intra-day and inter-day precision obtained by the microplate analyzer were less than 15 %. These results indicate that the microplate reader based detection technique has good accuracy, repeatability and reproducibility. A total of 700 volunteers were recruited, and 646 serum samples were tested for DPP-IV activity. The results showed that serum DPP-IV activity was higher in patients with T2DM than in controls (P < 0.01). However, the statistical data of family history of diabetes, gender and age of diabetic patients showed no statistical significance, and there was no contrast difference. The DPP-IV activity of serum in T2DM patients ranged from 2.4 µmol/min/L to 78.6 µmol/min/L, with a huge difference of up to 32-fold. These results suggest that it is necessary to test DPP-IV activity in patients with T2DM when taking DPP-IV inhibitors to determine the applicability of DPP-IV inhibitors in T2DM patients. These results suggest that it is necessary to detect the activity of DPP-IV in blood before taking DPP-IV inhibitors in patients with T2DM to judge the applicability of DPP-IV inhibitors in patients with T2DM.

A comparison of wild boar and domestic pig microbiota does not reveal a loss of microbial species but an increase in alpha diversity and opportunistic genera in domestic pigs.

The microbiome of wild animals is believed to be co-evolved with host species, which may play an important role in host physiology. It has been hypothesized that the rigorous hygienic practices in combination with antibiotics and diets with simplified formulas used in the modern swine industry may negatively affect the establishment and development of the gut microbiome. In this study, we evaluated the fecal microbiome of 90 domestic pigs sampled from nine farms in Canada and 39 wild pigs sampled from three different locations on two continents (North America and Europe) using 16S rRNA gene amplicon sequencing. Surprisingly, the gut microbiome in domestic pigs exhibited higher alpha-diversity indices than wild pigs (P < 0.0001). The wild pig microbiome showed a lower Firmicutes-to-Bacteroidetes ratio and a higher presence of bacterial phyla Elusimicrobiota, Verrucomicrobiota, Cyanobacteria, and Fibrobacterota when compared to their domestic counterparts. At the genus level, the wild pig microbiome had enriched genera that were known for fiber degradation and short-chain fatty acid production. Interestingly, the phylum Fusobacteriota was only observed in domestic pigs. We identified 31 ASVs that were commonly found in the pig gut microbiome, regardless of host sources, which could be recognized as members of the core gut microbiome. Interestingly, we found five ASVs missing in domestic pigs that were prevalent in wild ones, whereas domestic pigs harbored 59 ASVs that were completely absent in wild pigs. The present study sheds light on the impact of domestication on the pig gut microbiome, including the gain of new genera, which might provide the basis to identify novel targets to manipulate the pig gut microbiome for improved health. IMPORTANCE: The microbiome of pigs plays a crucial role in shaping host physiology and health. This study sought to identify if domestication and current rearing practices have resulted in a loss of co-evolved bacterial species by comparing the microbiome of wild boar and conventionally raised pigs. It provides a comparison of domestic and wild pigs with the largest sample sizes and is the first to examine wild boars from multiple sites and continents. We were able to identify core microbiome members that were shared between wild and domestic populations, and on the contrary to expectation, few microbes were identified to be lost from wild boar. Nevertheless, the microbiome of wild boars had a lower abundance of important pathogenic genera and was distinct from domestic pigs. The differences in the microbial composition may identify an opportunity to shift the microbial community of domestic pigs towards that of wild boar with the intent to reduce pathogen load.