Current Status of Poultry Recombinant Virus Vector Vaccine Development.

Inactivated and live attenuated vaccines are the mainstays of preventing viral poultry diseases. However, the development of recombinant DNA technology in recent years has enabled the generation of recombinant virus vector vaccines, which have the advantages of preventing multiple diseases simultaneously and simplifying the vaccination schedule. More importantly, some can induce a protective immune response in the presence of maternal antibodies and offer long-term immune protection. These advantages compensate for the shortcomings of traditional vaccines. This review describes the construction and characterization of primarily poultry vaccine vectors, including fowl poxvirus (FPV), fowl adenovirus (FAdV), Newcastle disease virus (NDV), Marek's disease virus (MDV), and herpesvirus of turkey (HVT). In addition, the pathogens targeted and the immunoprotective effect of different poultry recombinant virus vector vaccines are also presented. Finally, this review discusses the challenges in developing vector vaccines and proposes strategies for improving immune efficacy.

Development and characterization of a novel specific monoclonal antibody against mink enteritis virus and its antigen epitope analysis.

This study prepared a novel monoclonal antibody (MAb) against mink enteritis parvovirus (MEV) and identified its antigen epitope. The antibody subclass is identified as IgG1, the titers of the MAb is up to 1:1 × 106 and keeps stably after low-temperature storage for 9 months or 11 passages of the MAb cells. The MAb can specifically recognize MEV in the cells in IFA, but not Aleutian disease virus (ADV) or canine distemper virus (CDV). Its antigen epitope was identified as a polypeptide containing 5 key amino acids (378YAFGR382) and the homology in 20 MEV strains, 4 canine parvovirus strains, and 4 feline panleukopenia virus strains was 100%. This study supplies a biological material for developing new methods to detect MEV.

Clinical study of 57 cases of endovascular treatment for total subclavian artery occlusion.

OBJECTIVE: To investigate the safety and efficacy of endovascular treatment for totally occlusive lesions of the subclavian artery (SCA). METHODS: A retrospective study was performed on 57 patients treated with angioplasty and stenting, including 42 males and 15 females, with an average age of 61.8 years (range: 49 to 81 years). Efficacy, safety, and complications were evaluated. RESULTS: Procedural success was achieved for 47/57 patients and symptoms were relieved. Rat-tail occlusion is the most common type, and all cases were successfully recanalized. Plain type occlusion is less common with a recanalization rate of 55.6%. Hilly and plain occlusions are the main types of stent implantation failure. Through univariate analysis and trend matching analysis, the type of SCA occlusion and surgical approach had statistical significance on the success rate of surgery. The mean follow-up time was 34.6 ± 16.2 months. The cumulative stent patency rates at 1, 3, and 5 years were 95.5%, 86.4%, and 77.3% in the calcified plaque group and 92.0%, 76.0%, and 68.0% in the non-calcified plaque group, respectively. The 3-year and 5-year patency rates in the calcified plaque group were higher than those in the non-calcified plaque group (p < .05). CONCLUSION: Different occlusion types and surgical approaches can affect the surgical success rate. The combined femoral and brachial approach can improve the rate of recanalization of SCA occlusions. The patency rates at 3 and 5 years in the calcified plaque group were higher than those in the non-calcified plaque group.

Circ_0003945: an emerging biomarker and therapeutic target for human diseases.

Due to the rapid development of RNA sequencing techniques, a circular non-coding RNA (ncRNA) known as circular RNAs (circRNAs) has gradually come into focus. As a distinguished member of the circRNA family, circ_0003945 has garnered attention for its aberrant expression and biochemical functions in human diseases. Subsequent studies have revealed that circ_0003945 could regulate tumor cells proliferation, migration, invasion, apoptosis, autophagy, angiogenesis, drug resistance, and radio resistance through the molecular mechanism of competitive endogenous RNA (ceRNA) during tumorigenesis. The expression of circ_0003945 is frequently associated with some clinical parameters and implies a poorer prognosis in the majority of cancers. In non-malignant conditions, circ_0003945 also holds considerable importance in diseases pathogenesis. This review aims to recapitulate molecular mechanism of circ_0003945 and elucidates its potential as a diagnostic and therapeutic target in neoplasms and other diseases.

Preoperative Molecular Subtype Classification Prediction of Ovarian Cancer Based on Multi-Parametric Magnetic Resonance Imaging Multi-Sequence Feature Fusion Network.

In the study of the deep learning classification of medical images, deep learning models are applied to analyze images, aiming to achieve the goals of assisting diagnosis and preoperative assessment. Currently, most research classifies and predicts normal and cancer cells by inputting single-parameter images into trained models. However, for ovarian cancer (OC), identifying its different subtypes is crucial for predicting disease prognosis. In particular, the need to distinguish high-grade serous carcinoma from clear cell carcinoma preoperatively through non-invasive means has not been fully addressed. This study proposes a deep learning (DL) method based on the fusion of multi-parametric magnetic resonance imaging (mpMRI) data, aimed at improving the accuracy of preoperative ovarian cancer subtype classification. By constructing a new deep learning network architecture that integrates various sequence features, this architecture achieves the high-precision prediction of the typing of high-grade serous carcinoma and clear cell carcinoma, achieving an AUC of 91.62% and an AP of 95.13% in the classification of ovarian cancer subtypes.

Mixture-of-experts and semantic-guided network for brain tumor segmentation with missing MRI modalities.

Accurate brain tumor segmentation with multi-modal MRI images is crucial, but missing modalities in clinical practice often reduce accuracy. The aim of this study is to propose a mixture-of-experts and semantic-guided network to tackle the issue of missing modalities in brain tumor segmentation. We introduce a transformer-based encoder with novel mixture-of-experts blocks. In each block, four modality experts aim for modality-specific feature learning. Learnable modality embeddings are employed to alleviate the negative effect of missing modalities. We also introduce a decoder guided by semantic information, designed to pay higher attention to various tumor regions. Finally, we conduct extensive comparison experiments with other models as well as ablation experiments to validate the performance of the proposed model on the BraTS2018 dataset. The proposed model can accurately segment brain tumor sub-regions even with missing modalities. It achieves an average Dice score of 0.81 for the whole tumor, 0.66 for the tumor core, and 0.52 for the enhanced tumor across the 15 modality combinations, achieving top or near-top results in most cases, while also exhibiting a lower computational cost. Our mixture-of-experts and sematic-guided network achieves accurate and reliable brain tumor segmentation results with missing modalities, indicating its significant potential for clinical applications. Our source code is already available at https://github.com/MaggieLSY/MESG-Net .

Tenascin C activates the toll­like receptor 4/NF­κB signaling pathway to promote the development of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a globally prevalent gynecological disorder among women of childbearing age. The present study aimed to investigate the role of tenascin C (TNC) in PCOS and its potential mechanisms. Fasting blood glucose and serum insulin, the homeostasis model assessment of insulin resistance and the serum hormone levels were determined in PCOS rats. In addition, H&E staining was used for assessing pathology. In addition, the effects of TNC on oxidative stress and inflammation response in PCOS rat and cell models was assessed. Furthermore, the roles of TNC on KGN cell proliferation and apoptosis were determined employing EdU assay and flow cytometry. TLR4/NF­κB pathway­related proteins were measured using western blotting, immunofluorescence and immunohistochemistry. It was found that the mRNA and protein expression was upregulated in PCOS rats and in KGN cells induced by dihydrotestosterone (DHT). Knockdown of TNC relieved the pathological characteristics and the endocrine abnormalities of PCOS rats. Knockdown of TNC inhibited ovarian cell apoptosis, oxidative stress and inflammation in PCOS rats. Knockdown of TNC reversed the DHT­induced reduction in cell proliferation and increase in apoptosis in KGN cells. Furthermore, knockdown of TNC alleviated oxidative stress and inflammatory responses induced by DHT in KGN cells. Additionally, knockdown of TNC inhibited the toll­like receptor 4 (TLR4)/NF­κB signaling pathway in PCOS rats and DHT­treated KGN cells. In conclusion, knockdown of TNC could ameliorate PCOS in both rats and a cell model by inhibiting cell apoptosis, oxidative stress and inflammation via the suppression of the TLR4/NF­κB signaling pathway.

Targeted therapy of kidney disease with nanoparticle drug delivery materials.

With the development of nanomedicine, nanomaterials have been widely used, offering specific drug delivery to target sites, minimal side effects, and significant therapeutic effects. The kidneys have filtration and reabsorption functions, with various potential target cell types and a complex structural environment, making the strategies for kidney function protection and recovery after injury complex. This also lays the foundation for the application of nanomedicine in kidney diseases. Currently, evidence in preclinical and clinical settings supports the feasibility of targeted therapy for kidney diseases using drug delivery based on nanomaterials. The prerequisite for nanomedicine in treating kidney diseases is the use of carriers with good biocompatibility, including nanoparticles, hydrogels, liposomes, micelles, dendrimer polymers, adenoviruses, lysozymes, and elastin-like polypeptides. These carriers have precise renal uptake, longer half-life, and targeted organ distribution, protecting and improving the efficacy of the drugs they carry. Additionally, attention should also be paid to the toxicity and solubility of the carriers. While the carriers mentioned above have been used in preclinical studies for targeted therapy of kidney diseases both in vivo and in vitro, extensive clinical trials are still needed to ensure the short-term and long-term effects of nano drugs in the human body. This review will discuss the advantages and limitations of nanoscale drug carrier materials in treating kidney diseases, provide a more comprehensive catalog of nanocarrier materials, and offer prospects for their drug-loading efficacy and clinical applications.

White matter biomarker for predicting de novo Parkinson's disease using tract-based spatial statistics: a machine learning-based model.

Background: Parkinson's disease (PD) is an irreversible, chronic degenerative disease of the central nervous system, potentially associated with cerebral white matter (WM) lesions. Investigating the microstructural alterations within the WM in the early stages of PD can help to identify the disease early and enable intervention to reduce the associated serious threats to health. Methods: This study selected 227 cases from the Parkinson's Progression Markers Initiative (PPMI) database, including 152 de novo PD patients and 75 normal controls (NC). Whole-brain voxel analysis of the WM was performed using the tract-based spatial statistics (TBSS) method. The WM regions with statistically significant differences (P<0.05) between the PD and NC groups were identified and used as masks. The mask was applied to each case's fractional anisotropy (FA) image to extract voxel values as feature vectors. Geometric dimensionality reduction was then applied to eliminate redundant values in the feature vectors. Subsequently, the cases were randomly divided into a training group (158 cases, including 103 PD patients and 55 NC) and a test group (69 cases, including 49 PD patients and 20 NC). The least absolute shrinkage and selection operator (LASSO) regression algorithm was employed to extract the minimal set of relevant features, then the random forest (RF) algorithm was utilized for classification using 5-fold cross validation. The resulting model was further integrated with clinical factors to create a comprehensive prediction model. Results: In comparison to the NC group, the FA values in PD patients exhibited a statistically significant decrease (P<0.05), indicating the presence of widespread WM lesions across multiple brain regions. Moreover, the PD prediction model, constructed based on these WM lesion regions, yielded prediction accuracy (ACC) and area under the receiver operating characteristic (ROC) curve (AUC) values of 0.778 and 0.865 in the validation set, and 0.783 and 0.831 in the test set, respectively. Furthermore, the performance of the integrated model showed some improvement, with ACC and AUC values in the test set reaching 0.804 and 0.844, respectively. Conclusions: The quantitative calculation of WM lesion area on FA images using the TBSS method can serve as a neuroimaging biomarker for diagnosing and predicting early PD at the individual level. When integrated with clinical variables, the predictive performance improves.

MFN2 suppresses the accumulation of lipid droplets and the progression of clear cell renal cell carcinoma.

Dissolving the lipid droplets in tissue section with alcohol during a hematoxylin and eosin (H&E) stain causes the tumor cells to appear like clear soap bubbles under a microscope, which is a key pathological feature of clear cell renal cell carcinoma (ccRCC). Mitochondrial dynamics have been reported to be closely associated with lipid metabolism and tumor development. However, the relationship between mitochondrial dynamics and lipid metabolism reprogramming in ccRCC remains to be further explored. We conducted bioinformatics analysis to identify key genes regulating mitochondrial dynamics differentially expressed between tumor and normal tissues and immunohistochemistry and Western blot to confirm. After the target was identified, we created stable ccRCC cell lines to test the impact of the target gene on mitochondrial morphology, tumorigenesis in culture cells and xenograft models, and profiles of lipid metabolism. It was found that mitofusin 2 (MFN2) was downregulated in ccRCC tissues and associated with poor prognosis in patients with ccRCC. MFN2 suppressed mitochondrial fragmentation, proliferation, migration, and invasion of ccRCC cells and growth of xenograft tumors. Furthermore, MFN2 impacted lipid metabolism and reduced the accumulation of lipid droplets in ccRCC cells. MFN2 suppressed disease progression and improved prognosis for patients with ccRCC possibly by interrupting cellular lipid metabolism and reducing accumulation of lipid droplets.

Multi-organ segmentation: a progressive exploration of learning paradigms under scarce annotation.

Precise delineation of multiple organs or abnormal regions in the human body from medical images plays an essential role in computer-aided diagnosis, surgical simulation, image-guided interventions, and especially in radiotherapy treatment planning. Thus, it is of great significance to explore automatic segmentation approaches, among which deep learning-based approaches have evolved rapidly and witnessed remarkable progress in multi-organ segmentation. However, obtaining an appropriately sized and fine-grained annotated dataset of multiple organs is extremely hard and expensive. Such scarce annotation limits the development of high-performance multi-organ segmentation models but promotes many annotation-efficient learning paradigms. Among these, studies on transfer learning leveraging external datasets, semi-supervised learning including unannotated datasets and partially-supervised learning integrating partially-labeled datasets have led the dominant way to break such dilemmas in multi-organ segmentation. We first review the fully supervised method, then present a comprehensive and systematic elaboration of the 3 abovementioned learning paradigms in the context of multi-organ segmentation from both technical and methodological perspectives, and finally summarize their challenges and future trends.

Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization.

Alveolar bone regeneration has been strongly linked to macrophage polarization. M1 macrophages aggravate alveolar bone loss, whereas M2 macrophages reverse this process. Berberine (BBR), a natural alkaloid isolated and refined from Chinese medicinal plants, has shown therapeutic effects in treating metabolic disorders. In this study, we first discovered that culture supernatant (CS) collected from BBR-treated human bone marrow mesenchymal stem cells (HBMSCs) ameliorated periodontal alveolar bone loss. CS from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in vitro. To clarify the underlying mechanism, the bioactive materials were applied to different animal models. We discovered macrophage colony-stimulating factor (M-CSF), which regulates macrophage polarization and promotes bone formation, a key macromolecule in the CS. Injection of pure M-CSF attenuated experimental periodontal alveolar bone loss in rats. Colony-stimulating factor 1 receptor (CSF1R) inhibitor or anti-human M-CSF (M-CSF neutralizing antibody, Nab) abolished the therapeutic effects of the CS of BBR-treated HBMSCs. Moreover, AKT phosphorylation in macrophages was activated by the CS, and the AKT activator reversed the negative effect of the CSF1R inhibitor or Nab. These results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT axis. Further studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction sockets. Overall, our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.

miR-873-5p Suppression Reinvigorates Aging Mesenchymal Stem Cells and Improves Cardiac Repair after Myocardial Infarction.

Aging poses obstacles to the functionality of human mesenchymal stem cells (MSCs), resulting in a notable decline in their valuable contribution to myocardial infarction (MI). MicroRNAs (miRNAs) play a pivotal role in governing MSC aging; nonetheless, the specific mechanisms remain puzzling. This research delved into the value of miR-873-5p in the management of MSC aging and investigated whether the restraint of miR-873-5p could regenerate aged MSCs (AMSCs), thereby enhancing their healing success for MI. In this study, MSCs were isolated from both young donors (referred to as YMSCs) and aged donors (referred to as AMSCs). The senescence status of these MSCs was evaluated through the application of age-related ß-galactosidase (SA-ß-gal) staining. Following this assessment, the MSCs, including those treated with anti-miR-873-5p-AMSCs, were then transplanted into the hearts of Sprague-Dawley rats experiencing acute myocardial infarction. Increasing miR-873-5p levels in YMSCs resulted in elevated cellular aging, whereas reducing miR-873-5p expression decreased aging in AMSCs. Mechanistically, miR-873-5p inhibited autophagy in MSCs through the AMPK signaling pathway, leading to cellular aging by suppressing the Cab39 expression. Partial alleviation of these effects was achieved by the administration of the autophagy inhibitor 3-methyladenine. Grafting of anti-miR-873-5p-AMSCs, by enhancing angiogenesis and bolstering cell survival, led to an improvement in cardiac function in the rat model, unlike the transplantation of AMSCs. miR-873-5p which serves as a pivotal element in mediating MSC aging through its regulation of the Cab39/AMPK signaling pathway. It represents an innovative target for revitalizing AMSCs and enhancing their heart-protective abilities.

TFRC, associated with hypoxia and immune, is a prognostic factor and potential therapeutic target for bladder cancer.

BACKGROUND: Bladder cancer is a common malignancy of the urinary system, and the survival rate and recurrence rate of patients with muscular aggressive (MIBC) bladder cancer are not ideal. Hypoxia is a pathological process in which cells acquire special characteristics to adapt to anoxic environment, which can directly affect the proliferation, invasion and immune response of bladder cancer cells. Understanding the exact effects of hypoxia and immune-related genes in BLCA is helpful for early assessment of the prognosis of BLCA. However, the prognostic model of BLCA based on hypoxia and immune-related genes has not been reported. PURPOSE: Hypoxia and immune cell have important role in the prognosis of bladder cancer (BLCA). The aim of this study was to investigate whether hypoxia and immune related genes could be a novel tools to predict the overall survival and immunotherapy of BLCA patients. METHODS: First, we downloaded transcriptomic data and clinical information of BLCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A combined hypoxia and immune signature was then constructed on the basis of the training cohort via least absolute shrinkage and selection operator (LASSO) analysis and validated in test cohort. Afterwards, Kaplan-Meier curves, univariate and multivariate Cox and subgroup analysis were employed to assess the accuracy of our signature. Immune cell infiltration, checkpoint and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to investigate the immune environment and immunotherapy of BLCA patients. Furthermore, we confirmed the role of TFRC in bladder cancer cell lines T24 and UMUC-3 through cell experiments. RESULTS: A combined hypoxia and immune signature containing 8 genes were successfully established. High-risk group in both training and test cohorts had significantly poorer OS than low-risk group. Univariate and multivariate Cox analysis indicated our signature could be regarded as an independent prognostic factor. Different checkpoint was differently expressed between two groups, including CTLA4, HAVCR2, LAG3, PD-L1 and PDCD1. TIDE analysis indicated high-risk patients had poor response to immunotherapy and easier to have immune escape. The drug sensitivity analysis showed that high-risk group patients were more potentially sensitive to many drugs. Meanwhile, TFRC could inhibit the proliferation and invasion ability of T24 and UMUC-3 cells. CONCLUSION: A combined hypoxia and immune-related gene could be a novel predictive model for OS and immunotherapy estimation of BLCA patients and TFRC could be used as a potential therapeutic target in the future.

Comparison of preparation methods of rat kidney single-cell suspensions.

Preparation of kidney tissue single-cell suspensions is the basis of single-cell sequencing, flow cytometry and primary cell culture, but it is difficult to prepare high quality whole kidney single-cell suspensions because of the complex structure of the kidney. We explored a technique called stepwise enzymatic digestion (StE) method for preparing a single-cell suspension of rat whole kidney tissue which contained three main steps. The first step is to cut the kidney into a homogenate. The second step is the digestion of renal tubules using Multi Tissue Dissociation Kit 2 and the last step is the digestion of glomeruli using type IV collagenase. We also compared it with two previous techniques, mechanical grinding method and simple enzymatic digestion method. The StE method had the advantages of high intrinsic glomerular cells and immune cells harvest rate, high singlets rate and high cell viability compared with the other two techniques. In conclusion, the StE method is feasible, highly efficient, and worthy of further research and development.

Hybrid Ginseng-derived Extracellular Vesicles-Like Particles with Autologous Tumor Cell Membrane for Personalized Vaccination to Inhibit Tumor Recurrence and Metastasis.

Personalized cancer vaccines based on resected tumors from patients is promising to address tumor heterogeneity to inhibit tumor recurrence or metastasis. However, it remains challenge to elicit immune activation due to the weak immunogenicity of autologous tumor antigens. Here, a hybrid membrane cancer vaccine is successfully constructed by membrane fusion to enhance adaptive immune response and amplify personalized immunotherapy, which formed a codelivery system for autologous tumor antigens and immune adjuvants. Briefly, the functional hybrid vesicles (HM-NPs) are formed by hybridizing ginseng-derived extracellular vesicles-like particles (G-EVLPs) with the membrane originated from the resected autologous tumors. The introduction of G-EVLPs can enhance the phagocytosis of autologous tumor antigens by dendritic cells (DCs) and facilitate DCs maturation through TLR4, ultimately activating tumor-specific cytotoxic T lymphocytes (CTLs). HM-NPs can indeed strengthen specific immune responses to suppress tumors recurrence and metastasis including subcutaneous tumors and orthotopic tumors. Furthermore, a long-term immune protection can be obtained after vaccinating with HM-NPs, and prolonging the survival of animals. Overall, this personalized hybrid autologous tumor vaccine based on G-EVLPs provides the possibility of mitigating tumor recurrence and metastasis after surgery while maintaining good biocompatibility.

Germline Mutations of Holliday Junction Resolvase Genes in Multiple Primary Malignancies Involving Lung Cancer Lead to PARP Inhibitor Sensitization.

PURPOSE: The incidence of multiple primary malignancies (MPM) involving lung cancer has increased in recent decades. There is an urgent need to clarify the genetic profile of such patients and explore more efficacious therapy for them. EXPERIMENTAL DESIGN: Peripheral blood samples from MPM involving patients with lung cancer were assessed by whole-exome sequencing (WES), and the identified variants were referenced for pathogenicity using the public available database. Pathway enrichment analysis of mutated genes was performed to identify the most relevant pathway. Next, the effects of mutations in relevant pathway on function and response to targeted drugs were verified by in vitro and in vivo experiments. RESULTS: Germline exomes of 71 patients diagnosed with MPM involving lung cancer were sequenced. Pathway enrichment analysis shows that the homologous recombination repair (HRR) pathway has the strongest correlation. Moreover, HRR genes, especially key Holliday junction resolvases (HJR) genes (GEN1, BLM, SXL4, and RMI1), were most frequently mutated, unlike the status in the samples from patients with lung cancer only. Next, we identified a total of seven mutations in HJR genes led to homologous recombination DNA repair deficiency and rendered lung cancer cells sensitive to PARP inhibitor treatment, both in vitro and in vivo. CONCLUSIONS: This is the first study to map the profile of germline mutations in patients with MPM involving lung cancer. This study may shed light on early prevention and novel targeted therapies for MPM involving patients with lung cancer with HJR mutations.

Remote programming in stage I sacral neuromodulation: a multicentre prospective feasibility study.

OBJECTIVE: Sacral neuromodulation (SNM) has emerged as an effective therapy for refractory lower urinary tract dysfunction (LUTD). Remote programming holds promise in addressing the time and economic burdens associated with outpatient programming, especially for patients in the observation period following Stage I implant surgery (where the lead is implanted first without the pulse generator). The study aimed to explore the effectiveness and patient satisfaction of remote programming for Stage I SNM patients, and analyze the benefits patients gain from remote programming. METHODS: This prospective study was conducted at multiple high-level clinical SNM centres in China. Patients requiring SNM implantation were enroled and divided into two groups based on patient preference: remote programming (RP) group and outpatient control (OC) group. Patient attitudes toward RP were assessed through questionnaires, and the degree of symptom improvement was compared between the two groups to explore the usability of RP. RESULTS: A total of 63 participants from 6 centres were included in the study, with 32 belonging to the RP group. The remote programming system presents a high level of usability (98%) and willingness (satisfaction rate: 96.83%) in result of questionnaire. RP showed a significant advantage in improving patients' score of ICSI/ICPI (medianΔICSI/ICPI RP vs. OC= -13.50 vs -2, P =0.015). And slightly ameliorate urinary symptoms such as pain (medianΔVAS RP vs. OC= -1 vs 0, P = 0.164) and urgency (medianΔOBASS -2.5 vs. -1, P = 0.,229), but the difference was not statistically significant. RP did not significantly impact the quality of life of patients ( P =0.113), so do the rate of phase-two conversion ( P = 0.926) or programming parameters. CONCLUSION: To the best of our knowledge, the presented study is the first multicenter research focusing on the remote programming of Stage I SNM patients. Through the clinical implementation and patient feedback, we demonstrate that remote programming is not inferior to in-person programming in terms of success rate, effectiveness, safety, and patient satisfaction.

Bifunctional Tumor-Targeted Bioprobe for Phothotheranosis.

Background: Near-infrared (NIR) phototheranostics provide promising noninvasive imaging and treatment for head and neck squamous cell carcinoma (HNSCC), capitalizing on its adjacency to skin or mucosal surfaces. Activated by laser irradiation, targeted NIR fluorophores can selectively eradicate cancer cells, harnessing the power of synergistic photodynamic therapy and photothermal therapy. However, there is a paucity of NIR bioprobes showing tumor-specific targeting and effective phototheranosis without hurting surrounding healthy tissues. Methods: We engineered a tumor-specific bifunctional NIR bioprobe designed to precisely target HNSCC and induce phototheranosis using bioconjugation of a cyclic arginine-glycine-aspartic acid (cRGD) motif and zwitterionic polymethine NIR fluorophore. The cytotoxic effects of cRGD-ZW800-PEG were measured by assessing heat and reactive oxygen species (ROS) generation upon an 808-nm laser irradiation. We then determined the in vivo efficacy of cRGD-ZW800-PEG in the FaDu xenograft mouse model of HNSCC, as well as its biodistribution and clearance, using a customized portable NIR imaging system. Results: Real-time NIR imaging revealed that intravenously administered cRGD-ZW800-PEG targeted tumors rapidly within 4 h postintravenous injection in tumor-bearing mice. Upon laser irradiation, cRGD-ZW800-PEG produced ROS and heat simultaneously and exhibited synergistic photothermal and photodynamic effects on the tumoral tissue without affecting the neighboring healthy tissues. Importantly, all unbound bioprobes were cleared through renal excretion. Conclusions: By harnessing phototheranosis in combination with tailored tumor selectivity, our targeted bioprobe ushers in a promising paradigm in cancer treatment. It promises safer and more efficacious therapeutic avenues against cancer, marking a substantial advancement in the field.

Genome-Wide Identification and Characterization of the TIFY Gene Family and Their Expression Patterns in Response to MeJA and Aluminum Stress in Centipedegrass (Eremochloa ophiuroides).

The TIFY family is a group of novel plant-specific transcription factors involved in plant development, signal transduction, and responses to stress and hormones. TIFY genes have been found and functionally characterized in a number of plant species. However, there is no information about this family in warm-season grass plants. The current study identified 24 TIFY genes in Eremochloa ophiuroides, a well-known perennial warm-season grass species with a high tolerance to aluminum toxicity and good adaptability to the barren acidic soils. All of the 24 EoTIFYs were unevenly located on six out of nine chromosomes and could be classified into two subfamilies (ZIM/ZML and JAZ), consisting of 3 and 21 genes, respectively, with the JAZ subfamily being further divided into five subgroups (JAZ I to JAZ V). The amino acids of 24 EoTIFYs showed apparent differences between the two subfamilies based on the analysis of gene structures and conserved motifs. MCScanX analysis revealed the tandem duplication and segmental duplication of several EoTIFY genes occurred during E. ophiuroides genome evolution. Syntenic analyses of TIFY genes between E. ophiuroides and other five plant species (including A. thaliana, O. sativa, B. distachyon, S. biocolor, and S. italica) provided valuable clues for understanding the potential evolution of the EoTIFY family. qRT-PCR analysis revealed that EoTIFY genes exhibited different spatial expression patterns in different tissues. In addition, the expressions of EoTIFY genes were highly induced by MeJA and all of the EoTIFY family members except for EoJAZ2 displayed upregulated expression by MeJA. Ten EoTIFY genes (EoZML1, EoZML1, EoJAZ1, EoJAZ3, EoJAZ5, EoJAZ6, EoJAZ8, EoJAZ9, EoJAZ10, and EoJAZ21) were observed to be highly expressed under both exogenous MeJA treatment and aluminum stress, respectively. These results suggest that EoTIFY genes play a role in the JA-regulated pathway of plant growth and aluminum resistance as well. The results of this study laid a foundation for further understanding the function of TIFY genes in E. ophiuroides, and provided useful information for future aluminum tolerance related breeding and gene function research in warm-season grass plants.