Incidence and influencing factors of kinesiophobia in patients with chronic heart failure: a scoping review.

Introduction: Kinesiophobia denotes an excessive and irrational apprehension towards physical activity or exercise among patients, stemming from a perception of susceptibility to painful injury or re-injury. Cardiac rehabilitation stands pivotal in the secondary prevention spectrum for individuals with cardiovascular ailments, with exercise constituting a cornerstone of this regimen. However, the emergence of kinesiophobia poses a formidable challenge, diminishing patient adherence to cardiac rehabilitation protocols, particularly among those grappling with chronic heart failure. To bolster exercise-based rehabilitation initiatives in this cohort, a thorough comprehension of the multifaceted factors precipitating kinesiophobia is imperative. This review endeavors to delineate prevailing evidence and prevalence concerning kinesiophobia triggers in chronic heart failure patients, while pinpointing research lacunae for future exploration. Methods: Employing a scoping review methodology, our investigation culled data from diverse scholarly databases, including Embase, PubMed, Scopus, CINAHL, Web of Science, Medline, Sinomed, CNKI, Wangfan, and VIP. Results: After thorough evaluation, 9 studies that met the inclusion criteria were ultimately incorporated. Discussion: Our findings underscore a notable prevalence of kinesiophobia in chronic heart failure patients, predominantly influenced by socio-demographic factors, psychological and cognitive factors, disease and treatment factors, as well as lifestyle and behavior. Armed with these insights, future interventions can be tailored to mitigate kinesiophobia levels, fostering enhanced engagement in exercise-centric cardiac rehabilitation endeavors among patients grappling with chronic heart failure.

Discovery of a Novel Benzimidazole Derivative Targeting Histone Deacetylase to Induce Ferroptosis and Trigger Immunogenic Cell Death.

Ferroptosis is a unique type of cell death, characterized by its reliance on iron dependency and lipid peroxidation (LPO). Consequently, small-molecule ferroptosis modulators have garnered substantial interest as a promising avenue for cancer therapy. Herein, we explored the ferroptosis sensitivity of epigenetic modulators and found that the antiproliferative effects of class I histone deacetylase (HDAC) inhibitors are significantly reliant on ferroptosis. Subsequently, we developed a novel series of HDAC inhibitors, identifying HL-5s with robust inhibitory activity against class I HDACs, particularly HDAC1. Notably, HL-5s induces ferroptosis by augmenting LPO production. Mechanistically, HL-5s increased the YB-1 acetylation and inhibited the Nrf2/HO-1 signaling pathway. Furthermore, HL-5s not only significantly suppresses tumor growth in the PC-9 xenograft model but also remodels the tumor microenvironment in the LLC allograft model. Our study has unveiled that class I HDAC inhibitors can exert antitumor effects by triggering ferroptosis, and HL-5s may serve as a promising candidate for future cancer treatment.

Danggui-Shaoyao-San (DSS) ameliorating cognitive impairment in ischemia-reperfusion vascular dementia mice through miR-124 regulating PI3K/Akt signaling pathway.

Vascular dementia (VD) is a disease characterized by cognitive impairment and memory loss due to brain cell damage caused by cerebral vascular ischemia. Danggui-Shaoyao-San (DSS) has been used clinically to treat diseases for centuries. The VD model was established by bilateral common carotid artery (BCCA) repeated ischemia-reperfusion (I/R) and caudal bleeding. Target prediction of DSS and miR-124 in PI3K/Akt signaling pathway by network pharmacology. The effect of DSS on cognitive dysfunction were evaluated through methods such as behavioral experiments, cerebral blood flow monitoring, HE and Nissl staining, western blot, and q-PCR. Prediction result showed that both DSS and miR-124 could target Akt1. DSS treatment significantly reduced hippocampal cell damage, improved learning and memory ability. Mechanically, DSS treatment up-regulated the expression levels of PI3K and Akt protein, and its gene. Bcl-2/Bax index is up-regulated and cell apoptosis reduced. LC3II/LC3I index decreased and autophagy of brain cells increased. Moreover, DSS down-regulated the expression level of miR-124. And inhibition of miR-124 up-regulate the expression of PI3K, Akt. These results suggested that DSS can reduce the content of miR-124 in the hippocampus of VD mice, thus regulating the PI3K/Akt signaling pathway and improving the learning and memory ability of VD mice.

Comparative study of the clinical value of digital subtraction angiography via femoral and radial arterial paths.

OBJECTIVE: To evaluate the clinical efficacy of digital subtraction angiography (DSA) performed via femoral artery and radial artery approaches. METHODS: This retrospective study included 480 patients requiring cerebral vascular angiography at the First People's Hospital of Changde City from March 2020 to February 2022. Patients were divided into the femoral artery group (transfemoral approach, n=400) and the radial artery group (transradial approach, n=80) according to the surgical route. We compared perioperative metrics, success rates of selective angiography and puncture, and complication rates (including pseudoaneurysm, urinary retention, hematoma, vasospasm) between the groups. Multivariate logistic regression was used to analyze factors influencing the failure of angiography by each approach. RESULTS: The radial artery group exhibited shorter durations for puncture, hemostasis, exposure, operation, and postoperative recovery (all P<0.001). The success rate of selective angiography was higher in the radial artery group (93.75%) compared to the femoral artery group (85.25%) (χ2=4.168, P=0.041). No significant difference was found in puncture success rates between the groups (χ2=0.235, P=0.628). The overall complication rate was significantly lower in the radial artery group (2.50%) compared to the femoral artery group (9.25%) (χ2=4.069, P=0.044). Gender and low-density lipoprotein cholesterol levels were significant predictors of angiography failure in both approaches (both P<0.05). CONCLUSION: The transradial approach for DSA is safe and feasible, offering advantages in terms of operational time and complication rates, making it the preferred method in clinical settings.

Multilayered hydrogel scaffold construct with native tissue matched elastic modulus: A regenerative microenvironment for urethral scar-free healing.

The unsuitable deformation stimulus, harsh urine environment, and lack of a regenerative microenvironment (RME) prevent scaffold-based urethral repair and ultimately lead to irreversible urethral scarring. The researchers clarify the optimal elastic modulus of the urethral scaffolds for urethral repair and design a multilayered PVA hydrogel scaffold for urethral scar-free healing. The inner layer of the scaffold has self-healing properties, which ensures that the wound effectively resists harsh urine erosion, even when subjected to sutures. In addition, the scaffold's outer layer has an extracellular matrix-like structure that synergizes with adipose-derived stem cells to create a favorable RME. In vivo experiments confirm successful urethral scar-free healing using the PVA multilayered hydrogel scaffold. Further mechanistic study shows that the PVA multilayer hydrogel effectively resists the urine-induced inflammatory response and accelerates the transition of urethral wound healing to the proliferative phase by regulating macrophage polarization, thus providing favorable conditions for urethral scar-free healing. This study provides mechanical criteria for the fabrication of urethral tissue-engineered scaffolds, as well as important insights into their design.

Botanical characterization, phytochemistry, biosynthesis, pharmacology clinical application, and breeding techniques of the Chinese herbal medicine Fritillaria unibracteata.

Fritillaria unibracteata (FRU) belongs to the genus Fritillaria of the Liliaceae family. It is one of the original plants of the Chinese medicinal material "Chuanbeimu" and also a biological resource featured in the Tibetan Plateau of China. The dried bulbs of FRU are used in traditional Chinese medicine. The chemical constituents of FRU that have been isolated and identified include alkaloids, sterols, organic acids and their esters, nucleosides and volatile oils. FRU has antitussive, expectorant, anti-asthmatic, anti-inflammatory, antibacterial, acute lung injury-reducing, antifibrosis, antitumor, and other pharmacological effects. This valuable plant has an extremely high market demand, and over the years, due to over-exploitation, FRU has now been listed as a key species that is endangered and scarcely cultivated in China as a traditional Chinese medicinal herb. However, research on FRU is rare, and its effective components, resource control, and mechanisms of action need further study. This review systematically discusses the herbal characteristics, resource distribution, chemical composition, biosynthesis, pharmacological effects, clinical application, and breeding techniques of FRU, hoping to provide a reference for further research and the use of FRU.

TetR family regulator AbrT controls lincomycin production and morphological development in Streptomyces lincolnensis.

BACKGROUND: The TetR family of transcriptional regulators (TFRs), serving as crucial regulators of diverse cellular processes, undergo conformational changes induced by small-molecule ligands, which either inhibit or activate them to modulate target gene expression. Some ligands of TFRs in actinomycetes and their regulatory effects have been identified and studied; however, regulatory mechanisms of the TetR family in the lincomycin-producing Streptomyces lincolnensis remain poorly understood. RESULTS: In this study, we found that AbrT (SLCG_1979), a TetR family regulator, plays a pivotal role in regulating lincomycin production and morphological development in S. lincolnensis. Deletion of abrT gene resulted in increased lincomycin A (Lin-A) production, but delayed mycelium formation and sporulation on solid media. AbrT directly or indirectly repressed the expression of lincomycin biosynthetic (lin) cluster genes and activated that of the morphological developmental genes amfC, whiB, and ftsZ. We demonstrated that AbrT bound to two motifs (5'-CGCGTACTCGTA-3' and 5'-CGTACGATAGCT-3') present in the bidirectional promoter between abrT and SLCG_1980 genes. This consequently repressed abrT itself and its adjacent gene SLCG_1980 that encodes an arabinose efflux permease. D-arabinose, not naturally occurring as L-arabinose, was identified as the effector molecule of AbrT, reducing its binding affinity to abrT-SLCG_1980 intergenic region. Furthermore, based on functional analysis of the AbrT homologue in Saccharopolyspora erythraea, we inferred that the TetR family regulator AbrT may play an important role in regulating secondary metabolism in actinomycetes. CONCLUSIONS: AbrT functions as a regulator for governing lincomycin production and morphological development of S. lincolnensis. Our findings demonstrated that D-arabinose acts as a ligand of AbrT to mediate the regulation of lincomycin biosynthesis in S. lincolnensis. Our findings provide novel insights into ligand-mediated regulation in antibiotic biosynthesis.

Single-cell sequencing combined with spatial transcriptomics reveals that the IRF7 gene in M1 macrophages inhibits the occurrence of pancreatic cancer by regulating lipid metabolism-related mechanisms.

AIM: The main focus of this study is to explore the molecular mechanism of IRF7 regulation on RPS18 transcription in M1-type macrophages in pancreatic adenocarcinoma (PAAD) tissue, as well as the transfer of RPS18 by IRF7 via exosomes to PAAD cells and the regulation of ILF3 expression. METHODS: By utilising single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data from the Gene Expression Omnibus database, we identified distinct cell types with significant expression differences in PAAD tissue. Among these cell types, we identified those closely associated with lipid metabolism. The differentially expressed genes within these cell types were analysed, and target genes relevant to prognosis were identified. Flow cytometry was employed to assess the expression levels of target genes in M1 and M2 macrophages. Cell lines with target gene knockout were constructed using CRISPR/Cas9 editing technology, and cell lines with target gene knockdown and overexpression were established using lentiviral vectors. Additionally, a co-culture model of exosomes derived from M1 macrophages with PAAD cells was developed. The impact of M1 macrophage-derived exosomes on the lipid metabolism of PAAD cells in the model was evaluated through metabolomics analysis. The effects of M1 macrophage-derived exosomes on the viability, proliferation, division, migration and apoptosis of PAAD cells were assessed using MTT assay, flow cytometry, EdU assay, wound healing assay, Transwell assay and TUNEL staining. Furthermore, a mouse PAAD orthotopic implantation model was established, and bioluminescence imaging was utilised to assess the influence of M1 macrophage-derived exosomes on the intratumoural formation capacity of PAAD cells, as well as measuring tumour weight and volume. The expression of proliferation-associated proteins in tumour tissues was examined using immunohistochemistry. RESULTS: Through combined analysis of scRNA-seq and ST technologies, we discovered a close association between M1 macrophages in PAAD samples and lipid metabolism signals, as well as a negative correlation between M1 macrophages and cancer cells. The construction of a prognostic risk score model identified RPS18 and IRF7 as two prognostically relevant genes in M1 macrophages, exhibiting negative and positive correlations, respectively. Mechanistically, it was found that IRF7 in M1 macrophages can inhibit the transcription of RPS18, reducing the transfer of RPS18 to PAAD cells via exosomes, consequently affecting the expression of ILF3 in PAAD cells. IRF7/RPS18 in M1 macrophages can also suppress lipid metabolism, cell viability, proliferation, migration, invasion and intratumoural formation capacity of PAAD cells, while promoting cell apoptosis. CONCLUSION: Overexpression of IRF7 in M1 macrophages may inhibit RPS18 transcription, reduce the transfer of RPS18 from M1 macrophage-derived exosomes to PAAD cells, thereby suppressing ILF3 expression in PAAD cells, inhibiting the lipid metabolism pathway, and curtailing the viability, proliferation, migration, invasion of PAAD cells, as well as enhancing cell apoptosis, ultimately inhibiting tumour formation in PAAD cells in vivo. Targeting IRF7/RPS18 in M1 macrophages could represent a promising immunotherapeutic approach for PAAD in the future.

Effect of different food matrices on the bioaccessibility of vitamin D3 in beverage systems: Comparison between juice and liquid milk.

Vitamin D plays a crucial role in bone, immunology, and neurophysiological functions but has inadequate bioavailability in the human body. In this paper, six different liquid beverages were used for vitamin D3 fortification, investigating the effect of different food matrices on the bioaccessibility of vitamin D. Not from concentrate (NFC) apple juice (9.34%) and NFC orange juice (8.12%) presented about 20% higher bioaccessibility of vitamin D3 than soybean and skim milk, and achieved a similar value of whole milk (8.04%). Meanwhile, the bioaccessibility of NFC apple and orange juice was markedly about 120% higher than that of apple clear juice. From the correlation analysis, the bioaccessibility of VD3 indicated significant correlations with small intestine retention (0.82) and viscosity (0.66). But small intestinal particle size showed a negative effect on bioaccessibility (-0.78). Therefore, food components, delivery matrices, and physicochemical properties of digesta were key factors to achieve higher bioaccessibility for guiding formulation design.

Forensic age estimation in adults based on multidetector computed tomography analysis of bone density in the medial meta-epiphyseal region of clavicle.

The aim of this study was to investigate the potential of using multidetector computed tomography (MDCT) to measure the bone mineral density (BMD) in the medial meta-epiphyseal region of clavicle (MERC) for adult age estimation. A total of 1064 chest MDCT scans from individuals aged 21 to 102 years were utilized to determine the MERC BMD. The Mimics software was used for the BMD measurements, and the average BMD of both MERC was also calculated. Regression analysis was conducted with chronological age as a dependent variable and MERC BMD as an independent variable to establish a mathematical model for age estimation. The mean absolute error (MAE) was calculated to evaluate the accuracy of the regression model using an independent validation sample. Among all the models, the cubic regression model showed the highest correlation between MERC BMD and chronological age and also provided the most accurate age prediction for both males and females (MAE = 9.41 for males, MAE = 10.38 for females). Our study suggests that BMD measured by MERC can be utilized for age estimation in adults when more reliable indicators are not available.

p-Hydroxy benzaldehyde, a phenolic compound from Nostoc commune, ameliorates DSS-induced colitis against oxidative stress via the Nrf2/HO-1/NQO-1/NF-κB/AP-1 pathway.

BACKGROUND: Ulcerative colitis (UC), a chronic idiopathic inflammatory bowel disease (IBD), presents with limited current drug treatment options. Consequently, the search for safe and effective drug for UC prevention and treatment is imperative. Our prior studies have demonstrated that the phenolic compound p-Hydroxybenzaldehyde (HD) from Nostoc commune, effectively mitigates intestinal inflammation. However, the mechanisms underlying HD's anti-inflammatory effects remain unclear. PURPOSE: This study delved into the pharmacodynamics of HD and its underlying anti-inflammation mechanisms. METHODS: For in vivo experiments, dextran sodium sulfate (DSS)-induced colitis mouse model was established. In vitro inflammation model was established using lipopolysaccharide (LPS)-induced RAW264.7 and bone marrow-derived macrophages (BMDMs). The protective effect of HD against colitis was determined by monitoring clinical symptoms and histological morphology in mice. The levels of inflammatory factors and oxidative stress markers were subsequently analyzed with enzyme-linked immunosorbent assay (ELISA) and biochemical kits. Furthermore, western blotting (WB), immunofluorescence (IF), luciferase reporter gene, drug affinity reaction target stability (DARTS) assay, molecular docking, and molecular dynamics (MD) simulation were used to determine the potential target and molecular mechanism of HD. RESULTS: Our findings indicate that HD significantly alleviated the clinical symptoms and histological morphology of colitis in mice, and curtailed the production of pro-inflammatory cytokines, including TNF-α, IL-6, IFN-γ, COX-2, and iNOS. Furthermore, HD stimulated the production of SOD, CAT, and GSH-px, enhanced total antioxidant capacity (T-AOC), and reduced MDA levels. Mechanically, HD augmented the expression of Nrf2, HO-1, and NQO-1, while concurrently downregulating the phosphorylation of p65, IκBα, c-Jun, and c-Fos. ML385 and siNrf2 largely attenuated the protective effect of HD in enteritis mice and RAW 264.7 cells, as well as the promotion of HO-1 expression levels. ZnPP-mediated HO-1 knockdown reversed HD-induced inhibition of colonic inflammation. Luciferase reporter assay and IF assay confirmed the transcriptional activation of Nrf2 by HD. DARTS analysis, molecular docking, and MD results showed high binding strength, interaction efficiency and remarkable stability between Nrf2 and HD. CONCLUSION: These outcomes extend our previous research results that HD can combat oxidative stress through the Nrf2/HO-1/NQO-1/NF-κB/AP-1 pathways, effectively alleviating colitis, and propose new targets for HD to protect against intestinal barrier damage.

Effects of Glycosylation Combined with Phosphate Treatment on the Allergenicity and Structure of Tropomyosin in Litopenaeus vannamei.

Tropomyosin (TM) is the main allergen in shrimp (Litopenaeus vannamei). In this study, the effects of allergenicity and structure of TM by glycosylation (GOS-TM), phosphate treatment (SP-TM), and glycosylation combined with phosphate treatment (GOS-SP-TM) were investigated. Compared to GOS-TM and SP-TM, the IgG/IgE binding capacity of GOS-SP-TM was significantly decreased with 63.9 ± 2.0 and 49.7 ± 2.7%, respectively. Meanwhile, the α-helix content reduced, surface hydrophobicity increased, and 10 specific amino acids (K30, K38, S39, K48, K66, K74, K128, K161, S210, and K251) were modified by glycosylation on six IgE linear epitopes of GOS-SP-TM. In the BALB/c mice allergy model, GOS-SP-TM could significantly reduce the levels of specific IgE, IgG1, and CD4+IL-4+, while the levels of IgG2a, CD4+CD25+Foxp3+, and CD4+IFN-γ+ were increased, which equilibrated Th1 and Th2 cells, thus alleviating allergic symptoms. These results indicated that glycosylation combined with phosphate treatment can provide a new insight into developing hypoallergenic shrimp food.

Effect of transglutaminase-catalyzed glycosylation on the allergenicity of tropomyosin in the Perna viridis food matrix.

Food allergy is one of the hot issues in the field of food safety, and there have been a lot of concerns on how to reduce the allergenicity of food allergens. Food processing can change the allergenicity of allergens in the food matrix. In this study, ten IgE linear epitopes of the major allergen tropomyosin (TM) in Perna viridis were identified by bioinformatics prediction and serological experiments. The transglutaminase-catalyzed glycosylation modification sites glutamine, lysine and arginine were highly represented in the IgE linear epitopes of TM. The Perna viridis food matrix was treated with transglutaminase-catalyzed glycosylation. This reaction changed the secondary structure of protein in the food matrix, increased the content of ß-sheets and decreased the content of ß-turns. The intensity of intrinsic fluorescence and surface hydrophobicity were reduced. The IgE-binding activity of TM in the food matrix was reduced by modifying seven amino acid residues on six IgE linear epitopes. Transglutaminase-catalyzed glycosylation products decreased allergic symptoms in allergic mice, reduced the proportion of CD4+IL-4+ Th2 cells, and increased the proportion of CD4+IFN-γ+ Th1 cells and Treg cells. Mouse serum levels of IgE and IgG1 antibodies in the food matrix and TM were reduced. Therefore, this study provided a theoretical basis for the development of hypoallergenic Perna viridis products.

Artemisitene shows superiority over artemisinin in preventing Schistosoma japonica-induced liver disease.

BACKGROUND: Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, ß-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART. METHODS: We assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment. RESULTS: ATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms' surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART. CONCLUSION: ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART.

Ternary recognition fluorescent probe for lysosome acidification counter-ion studies via Cl-, K+, and pH.

Lysosomal acidity relies on H+ inflow, which requires counter-ion flows (Cl- and K+) to balance charge. A lysosome targeting ternary recognition fluorescent probe for Cl-, K+, and pH was developed for lysosome acidification counter-ion research. The probe was used to study counter-ion changes when the Cl- channel was blocked and under oxidative pressure.

Viral shedding pattern of severe fever with thrombocytopenia syndrome virus in severely ill patients: A prospective, Multicenter cohort study.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is spreading rapidly in Asia. The pathway of SFTS virus shedding from patient and specific use of personal protective equipments (PPEs) against viral transmission have rarely been reported. The study was to determine SFTS virus (SFTSV) shedding pattern from the respiratory, digestive and urinary tract to outside in patients. Methods: Patients were divided into mild and severe groups in three sentinel hospitals for SFTS in Anhui province from April 2020 to October 2022. SFTSV level from blood, throat swabs, fecal/anal swabs, urine and bedside environment swabs of SFTS patients were detected by qRT-PCR. Specific PPEs were applied in healthcare workers contacting with the patients who had oropharyngeal virus shedding and hemorrhagic signs. Results: A total of 189 SFTSV-confirmed patients were included in the study, 54 patients died (case fatality rate, 28.57 %). Positive SFTSV in throat swabs (T-SFTSV), fecal/anal swabs (F-SFTSV) and urine (U-SFTSV) were detected in 121 (64.02 %), 91 (48.15 %) and 65 (34.4 %) severely ill patients, respectively. The levels of T-SFTSV, F-SFTSV and U-SFTSV were positively correlated with the load of SFTSV in blood. We firstly revealed that SFTSV positive rate of throat swabs were correlated with occurrence of pneumonia and case fatality rate of patients (P < 0.0001). Specific precaution measures were applied by healthcare workers in participating cardiopulmonary resuscitation and orotracheal intubation for severely ill patients with positive T-SFTSV, no event of SFTSV human-to-human transmission occurred after application of effective PPEs. Conclusions: Our research demonstrated SFTSV could shed out from blood, oropharynx, feces and urine in severely ill patients. The excretion of SFTSV from these parts was positively correlated with viral load in the blood. Effective prevention measures against SFTSV human-to-human transmission are needed.

Value of fractional-order calculus (FROC) model diffusion-weighted imaging combined with simultaneous multi-slice (SMS) acceleration technology for evaluating benign and malignant breast lesions.

BACKGROUND: This study explores the diagnostic value of combining fractional-order calculus (FROC) diffusion-weighted model with simultaneous multi-slice (SMS) acceleration technology in distinguishing benign and malignant breast lesions. METHODS: 178 lesions (73 benign, 105 malignant) underwent magnetic resonance imaging with diffusion-weighted imaging using multiple b-values (14 b-values, highest 3000 s/mm2). Independent samples t-test or Mann-Whitney U test compared image quality scores, FROC model parameters (D,, ), and ADC values between two groups. Multivariate logistic regression analysis identified independent variables and constructed nomograms. Model discrimination ability was assessed with receiver operating characteristic (ROC) curve and calibration chart. Spearman correlation analysis and Bland-Altman plot evaluated parameter correlation and consistency. RESULTS: Malignant lesions exhibited lower D, and ADC values than benign lesions (P < 0.05), with higher values (P < 0.05). In SSEPI-DWI and SMS-SSEPI-DWI sequences, the AUC and diagnostic accuracy of D value are maximal, with D value demonstrating the highest diagnostic sensitivity, while value exhibits the highest specificity. The D and combined model had the highest AUC and accuracy. D and ADC values showed high correlation between sequences, and moderate. Bland-Altman plot demonstrated unbiased parameter values. CONCLUSION: SMS-SSEPI-DWI FROC model provides good image quality and lesion characteristic values within an acceptable time. It shows consistent diagnostic performance compared to SSEPI-DWI, particularly in D and values, and significantly reduces scanning time.

miR-340-3p-modified bone marrow mesenchymal stem cell-derived exosomes inhibit ferroptosis through METTL3-mediated m6A modification of HMOX1 to promote recovery of injured rat uterus.

BACKGROUND: Ferroptosis is associated with the pathological progression of hemorrhagic injury and ischemia-reperfusion injury. According to our previous study, exosomes formed through bone marrow mesenchymal stem cells modified with miR-340-3p (MB-exos) can restore damaged endometrium. However, the involvement of ferroptosis in endometrial injury and the effect of MB-exos on ferroptosis remain elusive. METHODS: The endometrial injury rat model was developed. Exosomes were obtained from the supernatants of bone marrow mesenchymal stromal cells (BMSCs) and miR-340/BMSCs through differential centrifugation. We conducted RNA-seq analysis on endometrial tissues obtained from the PBS and MB-exos groups. Ferroptosis was induced in endometrial stromal cells (ESCs) by treating them with erastin or RSL3, followed by treatment with B-exos or MB-exos. We assessed the endometrial total m6A modification level after injury and subsequent treatment with B-exos or MB-exos by methylation quantification assay. We performed meRIP-qPCR to analyze m6A modification-regulated endogenous mRNAs. RESULTS: We reveal that MB-exos facilitate the injured endometrium to recover by suppressing ferroptosis in endometrial stromal cells. The injured endometrium showed significantly upregulated N6-methyladenosine (m6A) modification levels; these levels were attenuated by MB-exos through downregulation of the methylase METTL3. Intriguingly, METTL3 downregulation appears to repress ferroptosis by stabilizing HMOX1 mRNA, thereby potentially elucidating the mechanism through which MB-exos inhibit ferroptosis in ESCs. We identified YTHDF2 as a critical m6A reader protein that contributes to HMOX1 mRNA degradation. YTHDF2 facilitates HMOX1 mRNA degradation by identifying the m6A binding site in the 3'-untranslated regions of HMOX1. In a rat model, treatment with MB-exos ameliorated endometrial injury-induced fibrosis by inhibiting ferroptosis in ESCs. Moreover, METTL3 short hairpin RNA-mediated inhibition of m6A modification enhanced the inhibitory effect of MB-exos on ferroptosis in endometrial injury. CONCLUSIONS: Thus, these observations provide new insights regarding the molecular mechanisms responsible for endometrial recovery promotion by MB-exos and highlight m6A modification-dependent ferroptosis inhibition as a prospective therapeutic target to attenuate endometrial injury.

Smart Bandage Based on a ZIF-8 Triboelectric Nanogenerator for In Situ Real-Time Monitoring of Drug Concentration.

For chronic wounds, frequent replacement of bandages not only increases the likelihood of secondary damage and the risk of cross infection but also wastes medication. Therefore, in situ real-time monitoring of the concentrations of residual drugs in bandages is crucial. Here, we propose a novel strategy that combines a triboelectric nanogenerator (TENG) with medical bandages to develop a smart bandage based on zeolite imidazolate framework TENG. During the process of wound healing, the electrical output of TENG changes with the continuous release of drugs. Based on the correlation between the electrical signal of TENG and drug concentration, the concentration of residual drugs in the bandage can be monitored in real-time in situ, guiding medical staff to replace the bandage at the most appropriate time. The smart bandage based on TENG provides a new strategy for in situ real-time monitoring of drug concentration and also provides an ideal and feasible solution for the field of biomedical drug sensing.

Accuracy of US CDC COVID-19 forecasting models.

Accurate predictive modeling of pandemics is essential for optimally distributing biomedical resources and setting policy. Dozens of case prediction models have been proposed but their accuracy over time and by model type remains unclear. In this study, we systematically analyze all US CDC COVID-19 forecasting models, by first categorizing them and then calculating their mean absolute percent error, both wave-wise and on the complete timeline. We compare their estimates to government-reported case numbers, one another, as well as two baseline models wherein case counts remain static or follow a simple linear trend. The comparison reveals that around two-thirds of models fail to outperform a simple static case baseline and one-third fail to outperform a simple linear trend forecast. A wave-by-wave comparison of models revealed that no overall modeling approach was superior to others, including ensemble models and errors in modeling have increased over time during the pandemic. This study raises concerns about hosting these models on official public platforms of health organizations including the US CDC which risks giving them an official imprimatur and when utilized to formulate policy. By offering a universal evaluation method for pandemic forecasting models, we expect this study to serve as the starting point for the development of more accurate models.