Advancements in artificial intelligence for pelvic floor ultrasound analysis.

Pelvic floor ultrasound provides a clear depiction of pelvic floor structures and their spatial anatomical relationships, enabling enhanced observation of pelvic organ function and position. The integration of artificial intelligence (AI) into medical imaging has revolutionized the automatic analysis of imaging data, offering efficient and accurate preprocessing and analysis. This technological advance addresses challenges associated with traditional pelvic floor ultrasound, such as reliance on operator's experience, time-intensive manual measurements, and significant potential for human error. Current AI applications in pelvic floor ultrasound encompass automatic measurement of the angle of progress (AOP), automatic segmentation of the levator hiatus (LH), and automatic identification of the levator ani muscle (LAM). AI excels in mimicking human analysis, distilling patterns from reorganized data. This paper, grounded in a comprehensive literature review, outlines the principal aspects of pelvic floor ultrasound and its augmentation through AI, highlighting the application value and progress of AI in this field.

Chasing weakly-bound biological water in aqueous environment near the peptide backbone by ultrafast 2D infrared spectroscopy.

There has been a long-standing debate as to how many hydrogen bonds a peptide backbone amide can form in aqueous solution. Hydrogen-bonding structural dynamics of N-ethylpropionamide (a ß-peptide model) in water was examined using infrared (IR) spectroscopy. Two amide-I sub bands arise mainly from amide C=O group that forms strong H-bonds with solvent water molecules (SHB state), and minorly from that involving one weak H-bond with water (WHB state). This picture is supported by molecular dynamics simulations and ab-initio calculations. Further, thermodynamics and kinetics of the SHB and WHB species were examined mainly by chemical-exchange two-dimensional IR spectroscopy, yielding an activation energy for the SHB-to-WHB exchange of 13.25 ± 0.52 kJ mol‒1, which occurs in half picosecond at room temperature. Our results provided experimental evidence of an unstable water molecule near peptide backbone, allowing us to gain more insights into the dynamics of the protein backbone hydration.

Photochemical Mn-Mediated Generation of Azide Radicals for Improvement of Alkene Hydroxyazidation.

State-of-the-art strategies for alkene-hydroxyazidation, which yield a mixture of ß-azido alcohol and ß-azido peroxide, must rely on phosphine reagents to improve the chemoselectivity. To overcome the above problems, we present a photochemical hydroxyazidation of alkenes via Mn-mediated ligand-to-metal charge transfer (LMCT) in O2, which activates N3- to •N3 and incorporates O2 to be used as an oxygen source in the hydroxyazidation products. Broad alkene range and step-economy chemistry for the hydroxyazidation transformation were also demonstrated.

Investigating the Impact of Electrostatic Interactions on Calmodulin Binding and Ca2+-Dependent Activation of the Calcium-Gated Potassium SK4 Channel.

Ca2+ binding to the ubiquitous Ca2+ sensing protein calmodulin (CaM) activates the intermediate conductance Ca2+-activated SK4 channel. Potential hydrophilic pockets for CaM binding have been identified at the intracellular HA and HB helices in the C-terminal of SK4 from the three published cryo-EM structures of SK4. Single charge reversal substitutions at either site, significantly weakened the pull-down of SK4 by CaM wild-type (CaM), and decreased the TRAM-34 sensitive outward K+ current densities in native HEK293T cells when compared with SK4 WT measured under the same conditions. Only the doubly substituted SK4 R352D/R355D (HB helix) obliterated the CaM-mediated pull-down and thwarted outward K+ currents. However, overexpression of CaM E84K/E87K, which had been predicted to face the arginine doublet, restored the CaM-mediated pull-down of SK4 R352D/R355D and normalized its whole-cell current density. Virtual analysis of the putative salt bridges supports a unique role for the positively charged arginine doublet at the HB helix into anchoring the interaction with the negatively charged CaM glutamate 84 and 87 CaM. Our findings underscore the unique contribution of electrostatic interactions in carrying CaM binding onto SK4 and support the role of the C-terminal HB helix to the Ca2+-dependent gating process.

Integrated lipid metabolomics and proteomics analysis reveal the pathogenesis of polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder that can lead to female infertility. Lipid metabolomics and proteomics are the new disciplines in systems biology aimed to discover metabolic pathway changes in diseases and diagnosis of biomarkers. This study aims to reveal the features of PCOS to explore its pathogenesis at the protein and metabolic level. METHODS: We collected follicular fluid samples and granulosa cells of women with PCOS and normal women who underwent in vitro fertilization(IVF) and embryo transfer were recruited. The samples were for the lipidomic study and the proteomic study based on the latest metabolomics and proteomics research platform. RESULTS: Lipid metabolomic analysis revealed abnormal metabolism of glycerides, glycerophospholipids, and sphingomyelin in the FF of PCOS. Differential lipids were strongly linked with the rate of high-quality embryos. In total, 144 differentially expressed proteins were screened in ovarian granulosa cells in women with PCOS compared to controls. Go functional enrichment analysis showed that differential proteins were associated with blood coagulation and lead to follicular development disorders. CONCLUSION: The results showed that the differential lipid metabolites and proteins in PCOS were closely related to follicle quality,which can be potential biomarkers for oocyte maturation and ART outcomes.

Developing and validating the nurse-patient relationship scale (NPRS) in China.

BACKGROUND: Poor nurse-patient relationship poses an obstacle to care delivery, jeopardizing patient experience and patient care outcomes. Measuring nurse-patient relationship is challenging given its multi-dimensional nature and a lack of well-established scales. PURPOSE: This study aimed to develop a multi-dimensional scale measuring nurse-patient relationship in China. METHODS: A preliminary scale was constructed based on the existing literature and Delphi consultations with 12 nursing experts. The face validity of the scale was tested through a survey of 45 clinical nurses. This was followed by a validation study on 620 clinical nurses. Cronbach's α, content validity and known-group validity of the scale were assessed. The study sample was further divided into two for Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA), respectively, to assess the construct validity of the scale. RESULTS: The Nurse-Patient Relationship Scale (NPRS) containing 23 items was developed and validated, measuring five dimensions: nursing behavior, nurse understanding and respect for patient, patient misunderstanding and mistrust in nurse, communication with patient, and interaction with patient. The Cronbach's α of the NPRS ranged from 0.725 to 0.932, indicating high internal consistency. The CFA showed excellent fitness of data into the five-factor structure: χ2/df = 2.431, GFI = 0.933, TLI = 0.923, CFI = 0.939, IFI = 0.923, RMSEA = 0.070. Good content and construct validity are demonstrated through expert consensus and psychometric tests. CONCLUSION: The NPRS is a valid tool measuring nurse-patient relationship in China.

Epigenomic mechanism regulating the quality and ripeness of apple fruit with differing harvest maturity.

Harvest maturity significantly affects the quality of apple fruit in post-harvest storage process. Although the regulatory mechanisms underlying fruit ripening have been studied, the associated epigenetic modifications remain unclear. Thus, we compared the DNA methylation changes and the transcriptional responses of mature fruit (MF) and immature fruit (NF). There were significant correlations between DNA methylation and gene expression. Moreover, the sugar contents (sucrose, glucose, and fructose) were higher in MF than in NF, whereas the opposite pattern was detected for the starch content. The expression-level differences were due to DNA methylations and ultimately resulted in diverse fruit textures and ripeness. Furthermore, the higher ethylene, auxin, and abscisic acid levels in MF than in NF, which influenced the fruit texture and ripening, were associated with multiple differentially expressed genes in hormone synthesis, signaling, and response pathways (ACS, ACO, ZEP, NCED, and ABA2) that were regulated by DNA methylations. Multiple transcription factor genes involved in regulating fruit ripening and quality via changes in DNA methylation were identified, including MIKCC-type MADS-box genes and fruit ripening-related genes (NAP, SPL, WRKY, and NAC genes). These findings reflect the diversity in the epigenetic regulation of gene expression and may be relevant for elucidating the epigenetic regulatory mechanism underlying the ripening and quality of apple fruit with differing harvest maturity.

Positive effects of parent-child group emotional regulation and resilience training on nonsuicidal self-injury behavior in adolescents: a quasi-experimental study.

Background: Nonsuicidal self-injury (NSSI) among adolescents is a growing global concern. However, effective interventions for treating NSSI are limited. Method: A 36-week quasi-experimental study design of parent-child group resilience training (intervention group) for adolescents aged 12-17 years was used and compared with treatment-as-usual (control group). The primary endpoint was the frequency of NSSI assessed with the Ottawa Self-Injury Inventory (OSI), and the secondary endpoints were the levels of depression, hope, resilience, and family adaptability and cohesion as assessed by the 24-item Hamilton depression rating scale (HAMD-24), Herth Hope Scale (HHS), Connor-Davidson Resilience Scale (CD-RISC), and Family Adaptability and Cohesion Evaluation Scale, second edition (FACES-II-CV), respectively. Result: A total of 118 participants completed the trial. Both groups showed a significant reduction in NSSI frequency after 12, 24, and 36 weeks of intervention (p< 0.05), although the intervention group did not differ significantly from the control group. After 12, 24, and 36 weeks of intervention, the CD-RISC, HHS, HAMD-24, and FACES-II-CV scores in the intervention and control groups improved over baseline (p< 0.05). Furthermore, the intervention group had higher scores on the CD-RISC, HHS, and FACES-II-CV and lower scores on the HAMD-24 than the control group after 12, 24, and 36 weeks of intervention (p  < 0.05). Conclusion: Parent-child group emotional regulation and resilience training showed promise as treatment options for NSSI among adolescents, leading to increased hope, resilience, and improved family dynamics among NSSI teens. Moreover, NSSI frequency significantly decreased in the intervention group compared to baseline.

Immune features revealed by single-cell RNA and single-cell TCR/BCR sequencing in patients with rheumatoid arthritis receiving COVID-19 booster vaccination.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, have profoundly affected human health. Booster COVID-19 vaccines have demonstrated significant efficacy in reducing infection and severe cases. However, the effects of booster COVID-19 vaccines on key immune cell subsets and their responses in rheumatoid arthritis (RA) are not well understood. By using single-cell RNA sequencing (scRNA-seq) combined with scTCR/BCR-seq analysis, a total of 8 major and 27 minor cell clusters were identified from paired peripheral blood mononuclear cells (PBMCs) which were collected 1 week before and 4 weeks after booster vaccination in stable RA patients. Booster vaccination only had limited impact on the composition and proportions of PBMCs cell clusters. CD8+ cytotoxic T cells (CD8+T_CTL) showed a trend toward an increase after vaccination, while naive B cells and conventional dendritic cells (cDCs) showed a trend toward a decrease. Transcriptomic changes were observed after booster vaccination, primarily involving T/B cell receptor signaling pathways, phagosome, antigen processing and presenting, and viral myocarditis pathways. Interferon (IFN) and pro-inflammatory response gene sets were slightly upregulated across most major cell subpopulations in COVID-19 booster-vaccinated RA individuals. Plasma neutralizing antibody titers significantly increased after booster COVID-19 vaccination (p = 0.037). Single-cell TCR/BCR analysis revealed increased B cell clone expansion and repertoire diversity postvaccination, with no consistent alterations in T cells. Several clonotypes of BCRs and TCRs were identified to be significantly over-represented after vaccination, such as IGHV3-15 and TRBV28. Our study provided a comprehensive single-cell atlas of the peripheral immune response and TCR/BCR immune repertoire profiles to inactivated SARS-CoV-2 booster vaccination in RA patients, which helps us to understand vaccine-induced immune responses better.

Recombinant hirudin suppresses angiogenesis of diffuse large B-cell lymphoma through regulation of the PAR-1-VEGF.

Hirudin is one of the specific inhibitors of thrombin, which has been confirmed to have strong bioactivities, including inhibiting tumors. However, the function and mechanism of hirudin and protease-activated receptor 1 (PAR-1) in diffuse large B-cell lymphoma (DLBCL) have not been clear. Detecting the expression PAR-1 in DLBCL tissues and cells by RT-qPCR and IHC. Transfected sh-NC, sh-PAR-1, or pcDNA3.1-PAR-1 in DLBCL cells or processed DLBCL cells through added thrombin, Vorapaxar, Recombinant hirudin (RH), or Na2S2O4 and co-culture with EA.hy926. And built DLBCL mice observed tumor growth. Detecting the expression of related genes by RT-qPCR, Western blot, IHC, and immunofluorescence, measured the cellular hypoxia with Hypoxyprobe-1 Kit, and estimated the cell inflammatory factors, proliferation, migration, invasion, and apoptosis by ELISA, CCK-8, flow cytometry, wound-healing and Transwell. Co-immunoprecipitation and pull-down measurement were used to verify the relationship. PAR-1 was highly expressed in DLBCL tissues and cells, especially in SUDHL2. Na2S2O4 induced SUDHL2 hypoxia, and PAR-1 did not influence thrombin-activated hypoxia. PAR-1 could promote SUDHL2 proliferation, migration, and invasion, and it was unrelated to cellular hypoxia. PAR-1 promoted proliferation, migration, and angiogenesis of EA.hy926 or SUDHL2 through up-regulation vascular endothelial growth factor (VEGF). RH inhibited tumor growth, cell proliferation, and migration, promoted apoptosis of DLBCL, and inhibited angiogenesis by down-regulating PAR-1-VEGF. RH inhibits proliferation, migration, and angiogenesis of DLBCL cells by down-regulating PAR-1-VEGF.

Static magnetic field-induced IL-6 secretion in periodontal ligament stem cells accelerates orthodontic tooth movement.

Static magnetic field (SMF) promoting bone tissue remodeling is a potential non-invasive therapy technique to accelerate orthodontic tooth movement (OTM). The periodontal ligament stem cells (PDLSCs), which are mechanosensitive cells, are essential for force-induced bone remodeling and OTM. However, whether and how the PDLSCs influence the process of inflammatory bone remodeling under mechanical force stimuli in the presence of SMFs remains unclear. In this study, we found that local SMF stimulation significantly enhanced the OTM distance and induced osteoclastogenesis on the compression side of a rat model of OTM. Further experiments with macrophages cultured with supernatants from force-loaded PDLSCs exposed to an SMF showed enhanced osteoclast formation. RNA-seq analysis showed that interleukin-6 (IL-6) was elevated in force-loaded PDLSCs exposed to SMFs. IL-6 expression was also elevated on the pressure side of a rat OTM model with an SMF. The OTM distance induced by an SMF was significantly decreased after injection of the IL-6 inhibitor tocilizumab. These results imply that SMF promotes osteoclastogenesis by inducing force-loaded PDLSCs to secrete the inflammatory cytokine IL-6, which accelerates OTM. This will help to reveal the mechanism of SMF accelerates tooth movement and should be evaluated for application in periodontitis patients.

Transcriptome and co-expression network revealed molecular mechanism underlying selenium response of foxtail millet (Setaria italica).

Introduction: Selenium-enriched foxtail millet (Setaria italica) represents a functional cereal with significant health benefits for humans. This study endeavors to examine the impact of foliar application of sodium selenite (Na2SeO4) on foxtail millet, specifically focusing on selenium (Se) accumulation and transportation within various plant tissues. Methods: To unravel the molecular mechanisms governing selenium accumulation and transportation in foxtail millet, we conducted a comprehensive analysis of selenium content and transcriptome responses in foxtail millet spikelets across different days (3, 5, 7, and 12) under Na2SeO4 treatment (200 µmol/L). Results: Foxtail millet subjected to selenium fertilizer exhibited significantly elevated selenium levels in each tissue compared to the untreated control. Selenate was observed to be transported and accumulated sequentially in the leaf, stem, and spikes. Transcriptome analysis unveiled a substantial upregulation in the transcription levels of genes associated with selenium metabolism and transport, including sulfate, phosphate, and nitrate transporters, ABC transporters, antioxidants, phytohormone signaling, and transcription factors. These genes demonstrated intricate interactions, both synergistic and antagonistic, forming a complex network that regulated selenate transport mechanisms. Gene co-expression network analysis highlighted three transcription factors in the tan module and three transporters in the turquoise module that significantly correlated with selenium accumulation and transportation. Expression of sulfate transporters (SiSULTR1.2b and SiSULTR3.1a), phosphate transporter (PHT1.3), nitrate transporter 1 (NRT1.1B), glutathione S-transferase genes (GSTs), and ABC transporter (ABCC13) increased with SeO4 2- accumulation. Transcription factors MYB, WRKY, and bHLH were also identified as players in selenium accumulation. Conclusion: This study provides preliminary insights into the mechanisms of selenium accumulation and transportation in foxtail millet. The findings hold theoretical significance for the cultivation of selenium-enriched foxtail millet.

Ectopic expression of HaPEPC1 from the desert shrub Haloxylon ammodendron confers drought stress tolerance in Arabidopsis thaliana.

Phosphoenolpyruvate carboxylase (PEPC) plays a crucial role in the initial carbon fixation process in C4 plants. However, its nonphotosynthetic functions in Haloxylon ammodendron, a C4 perennial xerohalophytic shrub, are still poorly understood. Previous studies have reported the involvement of PEPC in plant responses to abiotic stresses such as drought and salt stress. However, the underlying mechanism of PEPC tolerance to drought stress has not been determined. In this study, we cloned the C4-type PEPC gene HaPEPC1 from H. ammodendron and investigated its biological function by generating transgenic Arabidopsis plants with ectopic expression of HaPEPC1. Our results showed that, compared with WT (wild-type) plants, ectopic expression of HaPEPC1 plants exhibited significantly greater germination rates and chlorophyll contents. Furthermore, under drought stress, the transgenic plants presented increased root length, fresh weight, photosynthetic capacity, and antioxidant enzyme activities, particularly ascorbate peroxidase and peroxidase. Additionally, the transgenic plants exhibited reduced levels of malondialdehyde, H2O2 (hydrogen peroxide), and O2- (superoxide radical). Transcriptome analysis indicated that ectopic expression of HaPEPC1 primarily regulated the expression of genes associated with the stress defence response, glutathione metabolism, and abscisic acid (ABA) synthesis and signalling pathways in response to drought stress. Taken together, these findings suggest that the ectopic expression of HaPEPC1 enhances the reduction of H2O2 and O2- in transgenic plants, thereby improving reactive oxygen species (ROS) scavenging capacity and enhancing drought tolerance. Therefore, the HaPEPC1 gene holds promise as a candidate gene for crop selection aimed at enhancing drought tolerance.

Association between gene polymorphisms and initial warfarin therapy in patients after heart valve surgery.

BACKGROUND: Warfarin is widely used for the prevention and treatment of thrombotic events. This study aimed to examine the influence of gene polymorphisms on the early stage of warfarin therapy in patients following heart valve surgery. METHODS: Nine single nucleotide polymorphisms were genotyped using microarray chips, categorizing patients into three groups: normal responders (Group I), sensitive responders (Group II), and highly sensitive responders (Group III). The primary clinical outcomes examined were time in therapeutic range (TTR) and international normalized ratio (INR) variability. To investigate potential influencing factors, a generalized linear regression model was employed. RESULTS: Among 734 patients, the prevalence of CYP2C9*3-1075A > C, CYP2C19*3-636G > A, and CYP2C19*17-806C > T variants were 11.2%, 9.9%, and 1.9% of patients, respectively. VKORC1-1639G > A or the linked -1173C > T variant was observed in 99.0% of the patients. Generalized linear model analysis revealed an impact of sensitivity grouping on INR variability. Compared to Group I, Group II showed higher TTR values (p = 0.023), while INR variability was poorer in Group II (p < 0.001) and Group III (p < 0.001). Individual gene analysis identified significant associations between CYP2C9*3-1075A > C (p < 0.001), VKORC1-1639G > A or the linked -1173 C > T (p = 0.009) and GGCX-3261G > A (p = 0.019) with INR variability. CONCLUSION: The genotypes of CYP2C9, VKORC1, and GGCX were found to have a significant impact on INR variability during the initial phase of warfarin therapy. However, no significant association was observed between TTR and gene polymorphisms. These findings suggest that focusing on INR variability is crucial in clinical practice, and preoperative detection of gene polymorphisms should be considered to assist in the initiation of warfarin therapy.

Application of digital technology in the repair of functional and aesthetic defects in patients with acid erosion and severe attrition: a case report.

Noncarious lesions, a multifactorial condition encompassing tooth attrition, abrasion, and erosion, have a surge in prevalence and required increased attention in clinical practice. These nonbacterial-associated tooth defects can compromise aesthetics, phonetics, and masticatory functions. When providing full-arch fixed occlusal rehabilitation for such cases, the treatment strategy should extend beyond by restoring dentition morphology and aesthetics. This report details a complex case of erosive dental wear addressed through a fully digital, full-arch fixed occlusal rehabilitation. A 4D virtual patient was created using multiple digital data sources, including intraoral scanning, 3D facial scanning, digital facebow registration, and mandibular movement tracing. With a comprehensive understanding of the masticatory system, various types of microinvasive prostheses were customized for each tooth, including labial veneers, buccal-occlusal veneers, occlusal veneers, overlays, inlays, and full crowns, were customized for each tooth. The reported digital workflow offered a predictable diagnostic and treatment strategy, which was facilitated by virtual visualization and comprehensive quality control throughout the process.

Genome-wide identification and expression profiling of the ABI5 gene family in foxtail millet (Setaria italica).

BACKGROUND: ABA Insensitive 5 (ABI5) is a basic leucine zipper transcription factor that crucially influences plant growth, development, and stress response. However, there is minimal research on the ABI5 family in foxtail millet. RESULTS: In this study, 16 ABI5 genes were identified in foxtail millet, and their sequence composition, gene structures, cis-acting elements, chromosome positions, and gene replication events were analyzed. To more thoroughly evaluate the developmental mechanisms of the SiABI5 family during evolution, we selected three dicotyledons (S. lycopersicum, A. thaliana, F. tataricum) and three (Z. mays, O. sativa, S. bicolor) specific representative monocotyledons associated with foxtail millet for comparative homology mapping. The results showed that foxtail millet ABI5 genes had the best homology with maize. A promoter sequence analysis showed that the SiABI5s contain numerous cis-acting elements related to hormone and stress responses, indicating that the regulation of SiABI5 expression was complex. The expression responses of 16 genes in different tissues, seed germination, and ear development were analyzed. A total of six representative genes were targeted from five subfamilies to characterize their gene expression responses to four different abiotic stresses. Overexpression of SiABI5.12 confers tolerance to osmotic stress in transgenic Arabidopsis thaliana, which demonstrated the function of SiABI5 responded to abiotic stress. CONCLUSIONS: In summary, our research results comprehensively characterized the SiABI5 family and can provide a valuable reference for demonstrating the role of SiABI5s in regulating abiotic stress responses in foxtail millet.

Natural language processing to identify lupus nephritis phenotype in electronic health records.

BACKGROUND: Systemic lupus erythematosus (SLE) is a rare autoimmune disorder characterized by an unpredictable course of flares and remission with diverse manifestations. Lupus nephritis, one of the major disease manifestations of SLE for organ damage and mortality, is a key component of lupus classification criteria. Accurately identifying lupus nephritis in electronic health records (EHRs) would therefore benefit large cohort observational studies and clinical trials where characterization of the patient population is critical for recruitment, study design, and analysis. Lupus nephritis can be recognized through procedure codes and structured data, such as laboratory tests. However, other critical information documenting lupus nephritis, such as histologic reports from kidney biopsies and prior medical history narratives, require sophisticated text processing to mine information from pathology reports and clinical notes. In this study, we developed algorithms to identify lupus nephritis with and without natural language processing (NLP) using EHR data from the Northwestern Medicine Enterprise Data Warehouse (NMEDW). METHODS: We developed five algorithms: a rule-based algorithm using only structured data (baseline algorithm) and four algorithms using different NLP models. The first NLP model applied simple regular expression for keywords search combined with structured data. The other three NLP models were based on regularized logistic regression and used different sets of features including positive mention of concept unique identifiers (CUIs), number of appearances of CUIs, and a mixture of three components (i.e. a curated list of CUIs, regular expression concepts, structured data) respectively. The baseline algorithm and the best performing NLP algorithm were externally validated on a dataset from Vanderbilt University Medical Center (VUMC). RESULTS: Our best performing NLP model incorporated features from both structured data, regular expression concepts, and mapped concept unique identifiers (CUIs) and showed improved F measure in both the NMEDW (0.41 vs 0.79) and VUMC (0.52 vs 0.93) datasets compared to the baseline lupus nephritis algorithm. CONCLUSION: Our NLP MetaMap mixed model improved the F-measure greatly compared to the structured data only algorithm in both internal and external validation datasets. The NLP algorithms can serve as powerful tools to accurately identify lupus nephritis phenotype in EHR for clinical research and better targeted therapies.

Facile fabrication of a novel, photodetachable salecan-based hydrogel dressing with self-healing, injectable, and antibacterial properties based on metal coordination.

Achieving the controllable detachment of polysaccharide-based wound dressings is challenging. In this study, a novel, photodetachable salecan-based hydrogel dressing with injectable, self-healing, antibacterial, and wound healing properties was developed using a green and facile approach. A salecan hydrogel with a uniform porous structure and water content of 90.4 % was prepared by simply mixing salecan and an Fe3+-citric acid complexing solution in an acidic D-(+)-glucono-1,5-lactone environment. Metal coordinate interactions were formed between the released Fe3+ ions and carboxyl groups on the salecan polysaccharide, inducing homogeneous gelation. Benefiting from this dynamic and reversible crosslinking, the salecan hydrogel exhibited self-healing and injectable behavior, facilitating the formation of the desired shapes in situ. The exposure of Fe3+-citric acid to UV light (365 nm) resulted in the reduction of Fe3+ to Fe2+ through photochemical reactions, enabling phototriggered detachment. Moreover, the hydrogel exhibited excellent biocompatibility and satisfactory antibacterial efficacy against Escherichia coli and Staphylococcus aureus of 72.5 % and 85.3 %, respectively. The adhesive strength of the salecan hydrogel to porcine skin was 1.06 ± 0.12 kPa. In vivo wound healing experiments further highlighted the advantages of the prepared hydrogel in alleviating the degree of wound inflammation and promoting tissue regeneration within 12 days.

Heme oxygenase-1 is an equid alphaherpesvirus 8 replication restriction host protein and suppresses viral replication via the PKCß/ERK1/ERK2 and NO/cGMP/PKG pathway.

Equid alphaherpesvirus 8 (EqHV-8) is one of the most economically important viruses that is known to cause severe respiratory disease, abortion, and neurological syndromes in equines. However, no effective vaccines or therapeutic agents are available to control EqHV-8 infection. Heme oxygenase-1 (HO-1) is an antioxidant defense enzyme that displays significant cytoprotective effects against different viral infections. However, the literature on the function of HO-1 during EqHV-8 infection is little. We explored the effects of HO-1 on EqHV-8 infection and revealed its potential mechanisms. Our results demonstrated that HO-1 induced by cobalt-protoporphyrin (CoPP) or HO-1 overexpression inhibited EqHV-8 replication in susceptible cells. In contrast, HO-1 inhibitor (zinc protoporphyria) or siRNA targeting HO-1 reversed the anti-EqHV-8 activity. Furthermore, biliverdin, a metabolic product of HO-1, mediated the anti-EqHV-8 effect of HO-1 via both the protein kinase C (PKC)ß/extracellular signal-regulated kinase (ERK)1/ERK2 and nitric oxide (NO)-dependent cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathways. In addition, CoPP protected the mice by reducing the EqHV-8 infection in the lungs. Altogether, these results indicated that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.IMPORTANCEEqHV-8 infections have threatened continuously donkey and horse industry worldwide, which induces huge economic losses every year. However, no effective vaccination strategies or drug against EqHV-8 infection until now. Our present study found that one host protien HO-1 restrict EqHV-8 replication in vitro and in vivo. Furthermore, we demonstrate that HO-1 and its metabolite biliverdin suppress EqHV-8 relication via the PKCß/ERK1/ERK2 and NO/cGMP/PKG pathways. Hence, we believe that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.

Isolated myelin oligodendrocyte glycoprotein antibody-associated optic neuritis in adults: The importance of age of onset and prognosis-related radiological features.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) exhibits phenotypic diversity and it varies by age. However, less is known about whether the manifestations of isolated MOG antibody-associated optic neuritis (iMOG-ON) vary across different age groups. We aimed to investigate the clinical and prognostic features of iMOG-ON in young and middle-aged adult patients. METHODS: Patients with iMOG-ON were enrolled in the Department of Neurology, Beijing Tongren Hospital, Capital Medical University between January 2018 and October 2021. Medical records were reviewed to obtain clinical data and orbital MRI images of adult patients with iMOG-ON. Multivariate linear regression analysis was performed to investigate the associations between final best-corrected visual acuity (BCVA) in logMAR and clinical characteristics. RESULTS: Based on the age of onset, 70 patients were divided into 2 groups: 38 young (< 46 years; female/male = 0.76:1) and 32 middle-aged (≥ 46 years; female/male = 5.56:1) adults. There were statistical differences in both the female-to-male ratio and frequencies of contrast enhancement of the optic nerve sheaths and surrounding orbital tissues between both groups (p = 0.001, p = 0.004, respectively). The average follow-up periods were 28.04 ± 11.22 months. The median final BCVA was 0 (0 - 0.50) logMAR and 0.5 (0.3 - 1.0) logMAR in the young and middle-aged patients, respectively (p = 0.000). The multivariate linear regression analysis indicated significant positive relationships between final BCVA and age of onset (p = 0.038, 95 % CI: 0.020 - 0.728), sex (p = 0.030, 95 % CI: -0.793 - -0.042), BCVA at nadir (p = 0.000, 95 % CI: 0.164 - 0.386), and numbers of segments of optic nerve lesions (p = 0.009, 95 % CI: 0.068 - 0.450) with a coefficient of determination (R2) of 0.359 after adjusting for prior attacks of ON, time intervals between sudden-onset vision loss and administration of intravenous methylprednisolone, and corticosteroid dosages. The worst final BCVA was observed in afflicted eyes with lesions extending across three segments of the optic nerve. CONCLUSION: Compared to young adults with iMOG-ON, the middle-aged patients tended to have a female predominance, higher frequencies of perineural enhancement, and worse visual outcomes. In addition to age of onset, visual recovery may also be influenced by patient's sex, BCVA at nadir, and lengths of longitudinally expansive lesions of the optic nerve to a certain extent.