Metabolic landscape of human alveolar type II epithelial cells undergoing epithelial-mesenchymal transition induced directly by silica exposure.

Epithelial-mesenchymal transition (EMT) plays an irreplaceable role in the development of silicosis. However, molecular mechanisms of EMT induced by silica exposure still remain to be addressed. Herein, metabolic profiles of human alveolar type II epithelial cells (A549 cells) exposed directly to silica were characterized using non-targeted metabolomic approaches. A total of 84 differential metabolites (DMs) were identified in silica-treated A549 cells undergoing EMT, which were mainly enriched in metabolisms of amino acids (e.g., glutamate, alanine, aspartate), purine metabolism, glycolysis, etc. The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica. Remarkably, glutamine catabolism was significantly promoted in the silica-treated A549 cells, and the levels of related metabolites (e.g., succinate) and enzymes (e.g., α-ketoglutarate (α-KG) dehydrogenase) were substantially up-regulated, with a preference to α-KG pathway. Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail (zinc finger transcription factor). Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.

Liver transplantation following two conversions in a patient with huge hepatocellular carcinoma and portal vein invasion: A case report.

BACKGROUND: Surgical resection and liver transplantation (LT) are the most effective curative options for hepatocellular carcinoma (HCC). However, few patients with huge HCC (> 10 cm in diameter), especially those with portal vein tumor thrombus (PVTT), can receive these treatments. Selective internal radiation therapy (SIRT) can be used as a conversion therapy for them because it has the dual benefit of shrinking tumors and increasing residual hepatic volume. However, in patients with huge HCC, high lung absorbed dose often prevents them from receiving SIRT. CASE SUMMARY: A 35-year-old man was admitted because of emaciation and pain in the hepatic region for about 1 month. The computed tomography scan showed a 20.2 cm × 19.8 cm tumor located in the right lobe-left medial lobes with right portal vein and right hepatic vein invasion. After the pathological type of HCC was confirmed by biopsy, two conversions were presented. The first one was drug-eluting bead transarterial chemoembolization plus hepatic arterial infusion chemotherapy and lenvatinib and sintilimab, converted to SIRT, and the second one was sequential SIRT with continued systemic treatment. The tumor size significantly decreased from 20.2 cm × 19.8 cm to 16.2 cm × 13.8 cm, then sequentially to 7.8 cm × 6.8 cm. In the meantime, the ratio of spared volume to total liver volume increased gradually from 34.4% to 55.7%, then to 62.9%. Furthermore, there was visualization of the portal vein, indicating regression of the tumor thrombus. Finally, owing to the new tumor in the left lateral lobe, the patient underwent LT instead of resection without major complications. CONCLUSION: Patients with inoperable huge HCC with PVTT could be converted to SIRT first and accept surgery sequentially.

Lignin Nanofiber Flexible Carbon Aerogels for self-standing supercapacitors.

Renewable feedstocks are sought for clean technology applications, including energy storage applications. In this study, LignoForce™ lignin, a biobased aromatic polymer commercially isolated from wood, was fractioned into two parts using acetone, and the resulting lignin fractions had distinct thermo-rheological behavior. These two fractionated lignins were combined in various ratios and transformed into nanofibers by electrospinning. Subsequently, electrospun fiber materials were disrupted by agitating the mats in water, and the materials were transformed into ultralight 3D aerogels through lyophilization and post-process controlled heating. Using only this combination of two fractions, the morphology of lignin nanofibers was tailored by heat treatment, resulting in lignin aerogels with high flexibility and significant shape recovery properties. Various microscale structures of lignin fibers impacted the resulting physical properties of the elastic aerogel materials, such as resilience, compressive strength, and electrical conductivity for the corresponding carbonized samples. By exploiting lignin's sensitivity to heat and tailoring the thermal properties of the lignin through fractionation, the work provided an interesting path to form robust lignin-derived functional materials without any toxic chemical additives and significant ability to serve as free-standing electrodes with specific capacitance values better than some graphene-based supercapacitors.

Sacubitril/valsartan attenuated myocardial inflammation, fibrosis, apoptosis and promoted autophagy in doxorubicin-induced cardiotoxicity mice via regulating the AMPKα-mTORC1 signaling pathway.

This study aimed to investigate the potential cardioprotective effects of sacubitril/valsartan (Sac/Val) in mice with doxorubicin (DOX)-induced cardiomyopathy, a common manifestation of cancer therapy-related cardiac dysfunction (CTRCD) associated with DOX. A total of thirty-two mice were equally classified into 4 groups: control group, DOX (total 24 mg/kg), Sac/Val (80 mg/kg), and Sac/Val + DOX (Sac/Val was given from seven days before doxorubicin administration). Neonatal rat ventricular myocytes was exposed to 5 µM of DOX for 6 h in vitro to mimic the in vivo conditions. A variety of techniques were used to investigate cardiac inflammation, fibrosis, apoptosis, and autophagy, including western blot, real-time quantitative PCR (RT-qPCR), immunohistochemistry, and fluorescence. Mice with DOX-induced cardiotoxicity displayed impaired systolic and diastolic function, characterized by elevated levels of cardiac inflammation, fibrosis, cardiomyocyte hypertrophy, apoptosis, and autophagy inhibition in the heart. Treatment with Sac/Val partially reversed these effects. In comparison to the control group, the protein expression of NLRP3, caspase-1, collagen I, Bax, cleaved caspase-3, and P62 were significantly increased, while the protein expression of Bcl-2 and LC3-II were significantly decreased in the myocardial tissues of the Dox-induced cardiomyopathy group. The administration of Sac/Val demonstrated the potential to partially reverse alterations in protein expression within the myocardium of mice with DOX-induced cardiotoxicity by modulating the AMPKα-mTORC1 signaling pathway and suppressing oxidative stress. Additionally, Sac/Val treatment may mitigate Dox-induced apoptosis and inhibition of autophagy in primary cardiomyocytes. Sac/Val seems to be cardioprotective against DOX-induced cardiotoxicity in the pre-treatment mice model. These findings could be attributed to the anti-inflammatory, antioxidant, anti-apoptotic, and de-autophagy effects of Sac/Val through regulation of the AMPKα-mTORC1 signaling pathway.

Cathepsin B modulates microglial migration and phagocytosis of amyloid ß in Alzheimer's disease through PI3K-Akt signaling.

The approval of anti-amyloid ß (Aß) monoclonal antibodies (lecanemab) for the treatment of patients with early preclinical stage of Alzheimer's disease (AD) by the Food and Drug Administration, suggests the reliability and importance of brain Aß clearance for AD therapy. Microglia are the main phagocytes that clear Aß in the brain, but the underlying regulatory mechanism is unclear. Here, we investigate the critical role of cathepsin B (CatB) in modulating microglial Aß clearance from mouse brain. Wild-type or CatB-/- mice were injected with Aß into the hippocampus from 1 to 3 weeks. Mice were evaluated for cognitive change, Aß metabolism, neuroinflammation. Microglia and neuron cultures were prepared to verify the in vivo results. The statistical analyses were performed by student's t test, one-way ANOVA with a post hoc Tukey's test using the GraphPad Prism software package. CatB deficiency significantly reduces Aß clearance efficiency and aggravates mouse cognitive decline. Exogenous Aß markedly increases CatB expression in activated microglia. Transcriptome analysis and in vitro cell culture experiments demonstrate that CatB is associated with gene clusters involved in migration, phagocytosis, and inflammation. In addition, transcriptome analysis and immunoblotting suggest that CatB modulates microglial Aß clearance via PI3K-AKT activation. Our study unveils a previously unknown role of CatB in promoting microglial functionality during Aß clearance.

Postmarketing adverse events of tamoxifen in male and female patients with breast cancer.

Tamoxifen (TAM), a selective estrogen receptor (ER) modulator, has received approval for use in patients with breast cancer (BC) exhibiting positive ER expression. Given the widespread clinical use of TAM, a comprehensive real-world study of its adverse events (AEs) is warranted. The database for analysis, sourced from the Food and Drug Administration Adverse Event Reporting System (FAERS), covers the period from the first quarter of 2014 to the third quarter of 2023. A disproportionality analysis was conducted to quantify the correlation between TAM and AEs. Subgroup analyses were performed to identify differences between BC AEs in males and females receiving TAM, aiming to assess the risk factors of male BC AEs. Total 4890 reports indicated BC, with 91 and 4190 specifically linked to AEs in male and female patients with BC, respectively. Male-specific AE was libido decreased (reporting odds ratio [ROR]: 43.33), and female-specific AE was uterine disease, including sarcoma uterus (ROR: 519.51), endometrial cancer (ROR: 131.26), uterine polyp (ROR: 40.83), endometriosis (ROR: 11.39), among others. A notably higher risk of AEs in male patients with BC was observed in individuals aged >65 years (χ2 = 20.83, p < .001). Male patients with BC had a relatively higher risk of hospitalization (χ2 = 4.83, p = .03) and a lower risk of deaths (χ2 = 5.32, p = .02). Theses finding may assist healthcare professionals in recognizing the TAM-associated AEs and understanding gender differences, potentially improving safety in clinical applications.

Pain Interference in Juvenile Idiopathic Arthritis.

OBJECTIVE: Despite treatment advances, pain remains a serious problem for many children with juvenile idiopathic arthritis (JIA). To better understand pain in children with JIA and identify potentially modifiable factors, this study evaluated Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Pain Interference (PI) and its relationships with other pain measures and demographic, clinical, psychosocial, and functional variables. METHODS: This cross-sectional, observational, multicenter study used descriptive statistics and a mix of bivariate and multivariable analyses to describe PI and characterize relationships with other measures and variables. RESULTS: Among 355 children with JIA, 27% reported moderate or severe PI and 13.3% reported daily pain. PI correlated with other pain measures. Increasing age, decreasing disease duration, and increasing number of active joints, as well as presence of active disease, steroid treatment, and biologic treatment, were associated with greater PI. All PROMIS psychosocial and functional measures were associated with PI in the expected direction except for PROMIS Pediatric Physical Activity, which showed no association. In multivariable analyses, only PROMIS Fatigue, PROMIS Mobility, and the exploratory interaction of PROMIS Anxiety and disease-modifying antirheumatic drug treatment were significant. CONCLUSION: Moderate and severe PI was prevalent in this sample of children with JIA. PI increased with age and indicators of disease activity, but was more strongly associated with increasing fatigue and decreasing mobility. Findings support the use of PI as a short, easily administered multidimensional pain measure as part of routine clinical care. Fatigue, mobility, and disease activity should be assessed further when PI is high.

Gut microbiota: Implications in pathogenesis and therapy to cardiovascular disease (Review).

The gut microbiota refers to the diverse bacterial community residing in the gastrointestinal tract. Recent data indicate a strong correlation between alterations in the gut microbiota composition and the onset of various diseases, notably cardiovascular disorders. Evidence suggests the gut-cardiovascular axis signaling molecules released by the gut microbiota play a pivotal role in regulation. This review systematically delineates the association between dysbiosis of the gut microbiota and prevalent cardiovascular diseases, including atherosclerosis, hypertension, myocardial infarction and heart failure. Furthermore, it provides an overview of the putative pathogenic mechanisms by which dysbiosis in the gut microbiota contributes to the progression of cardiovascular ailments. The potential modulation of gut microbiota as a preventive strategy against cardiovascular diseases through dietary interventions, antibiotic therapies and probiotic supplementation is also explored and discussed within the present study.

Unpredicted protective function of Fc-mediated inhibitory antibodies for HIV and SARS-CoV-2 vaccines.

Developing effective vaccines is necessary in combating new virus pandemics. For HIV and SARS-CoV-2, the induction of neutralizing antibodies (NAb) is important for vaccine protection; however, the exact mechanisms underlying protection require further study. Recent data emphasize that even Abs that do not exhibit neutralizing activity may contribute to immune defense. Abs exhibiting this function may counter virus mutations, which are acquired to escape from NAbs, and therefore, broaden the protective Ab response induced by vaccination. However, the steps leading to Ab Fc-mediated inhibition are complex. How can these functions be measured in vitro? What inhibitory assay is the most physiologically relevant at mimicking effective in vivo protection? This review provides a comprehensive update on the current knowledge gaps on the Ab Fc-mediated functions involved in HIV and SARS-CoV-2 protection. Understanding the inhibitory effects of these Abs is vital for designing the next generation of protective HIV and SARS-CoV-2 vaccines.

Intelligent identification of picking periods of Lu'an Guapian tea by an indicator displacement colorimetric sensor array combined with machine learning.

Lu'an Gua Pian (LAGP) tea is one of the most famous green teas in China. The quality of green tea is related to its picking periods, especially the green tea before Qingming Festival (usually April 6th) is highly praised as precious in the market. In this work, a simple and cheap indicator displacement colorimetric sensor array combined with smartphone was developed to rapidly identify LAGP picked during different picking periods. First, the chemical component contents of LAGP picked before and after Qingming Festival were analyzed. Second, a well-designed colorimetric sensor array was proposed based on the tea component contents differences. Finally, machine learning was used to process the array data taken by a smartphone. By comparison, the accuracy of the best model for the prediction set was 97%. Meanwhile, the multi-channel advantages of the sensing array were demonstrated by an ablation experiment. In addition, the method achieved an AGREE analysis score of 0.88, indicating that it was environmental-friendly.

Outdoor light at night is a modifiable environmental factor for metabolic syndrome: The 33 Communities Chinese Health Study (33CCHS).

Metabolic syndrome (MetS) is a significant public health problem and presents an escalating clinical challenge globally. To combat this problem effectively, urgent measures including identify some modifiable environmental factors are necessary. Outdoor artificial light at night (LAN) exposure garnered much attention due to its impact on circadian rhythms and metabolic process. However, epidemiological evidence on the association between outdoor LAN exposure and MetS remains limited. To determine the relationship between outdoor LAN exposure and MetS, 15,477 adults participated the 33 Communities Chinese Health Study (33CCHS) in 2009 were evaluated. Annual levels of outdoor LAN exposure at participants' residential addresses were assessed using satellite data from the Defense Meteorological Satellite Program (DMSP) Operational Linescan System (OLS). Generalized linear mixed effect models were utilized to assess the association of LAN exposure with MetS and its components, including elevated waist circumference (WC), triglycerides (TG), blood pressure (BP), fasting blood glucose (FBG), and reduced high-density lipoprotein cholesterol (HDL-C). Effect modification by various social demographic and behavior factors was also examined. Overall, 4701 (30.37 %) participants were defined as MetS. The LAN exposure ranged from 6.03 to 175.00 nW/cm2/sr. The adjusted odds ratio (OR) of MetS each quartile increment of LAN exposure were 1.43 (95 % CI: 1.21-1.69), 1.44 (95 % CI: 1.19-1.74) and 1.52 (95 % CI: 1.11-2.08), respectively from Q2-Q4. Similar adverse associations were also found for the components of MetS, especially for elevated BP, TG and FBG. Interaction analyses indicated that the above associations were stronger in participants without habitual exercise compared with those with habitual exercise (e.g. OR were 1.52 [95 % CI: 1.28-1.82] vs. 1.27 [95 % CI, 1.04-1.55], P-interaction = 0.042 for MetS). These findings suggest that long-term exposure to LAN can have a significant deleterious effect on MetS, potentially making LAN an important modifiable environmental factor to target in future preventive strategies.

Proliferation capability of natural killer cells upon cytokines stimulation correlated negatively with serum lactate dehydrogenase level in coronary artery disease patients.

Background: Natural killer (NK) cells are proposed to participate in coronary artery disease (CAD) development. However, little is known about how CAD patients' NK cells respond to different stimulatory factors in terms of proliferation capability. Methods and results: Twenty-nine CAD patients' peripheral blood NK cells were isolated and individually treated with IL-2, IL-12, IL-15, IL-18, IL-21, cortisone acetate, hydrocortisone, or ascorbic acid for 36 hours, followed by cell cycle analysis using flow cytometry. The ratio of S and G2/M phase cell number to total cell number was defined as a proliferation index (PrI) and used for proliferative capability indication. The results showed that these eight factors resulted in different life cycle changes in the 29 NK cell samples. Remarkably, 28 out of 29 NK cell samples showed an obvious increase in PrI upon ascorbic acid treatment. The serum lactate dehydrogenase (LDH) level of the 29 CAD patients was measured. The results showed a negative correlation between serum LDH level and the CAD patients' NK cell PrI upon stimulation of interleukins, but not the non-interleukin stimulators. Consistently, a retrospective analysis of 46 CAD patients and 32 healthy donors showed that the circulating NK cell number negatively correlated with the serum LDH level in CAD patients. Unexpectedly, addition of LDH to NK cells significantly enhanced the production of IFN-γ, IL-10 and TNF-α, suggesting a strong regulatory role on NK cell's function. Conclusion: Ascorbic acid could promote the proliferation of the CAD patients' NK cells; LDH serum level may function as an indicator for NK cell proliferation capability and an immune-regulatory factor.

Combinatory effect of ALA-PDT and itraconazole in the treatment of cutaneous protothecosis.

BACKGROUND: As a rare subcutaneous infection, protothecosis is easily misdiagnosed. Similar to other subcutaneous infection, there is no unified standard for treatment, for cases not suitable for surgery, clinicians often use antifungal drugs based on their experience, and the course of treatment varies from several months to several years. Based on the fact that there are few relevant materials and researches on photodynamic therapy (PDT), we conducted a study based on a clinical case that used oral itraconazole combined with 5-aminolevylinic acid photodynamic therapy (ALA-PDT) to treat a patient with cutaneous protothecosis caused by Prototheca wicherhamii. METHODS: Different concentrations of ALA and different light doses were used to investigate the effects of ALA-PDT on the growth inhibition of P. wickerhamii in vitro with Colony-counting Methods. And we used transmission electron microscopy (TEM) to visualize the structural changes and the effects of ALA-PDT treating on cellular structures of the P. wickerhamii. Futher, we performed the susceptibility test of P. wickerhamii to itraconazole before and after ALA-PDT in vitro. RESULTS: We have successfully treated a patient with cutaneous protothecosis caused by P. wickerhamii by using combination therapy in a total of 9-week course of treatment. In vitro, ALA-PDT can inhibit the growth of P. wickerhamii when the ALA concentration was 5 mg/mL (P < 0.01), and this effect became stronger as the concentration of ALA or light dose is increased. Using TEM, we confirmed that ALA-PDT can disrupt the cell wall structure and partition structure of P. wickerhamii, which may contribute to its inhibitory effect. Further studies showed that the MIC of itraconazole for P. wickerhamii was decreased after ALA-PDT. CONCLUSIONS: ALA-PDT combined with oral itraconazole can be used to treat cutaneous protothecosis. Accordingly, ALA-PDT can destroy the cell wall and partition structure of P. wickerhamii leading to an inhibitory effect on it in vitro, and the effect is enhanced with the increase of ALA concentration and light dose. Also, the sensitivity of P. wickerhamii to itraconazole is observed increased after ALA-PDT. So our study provides a theoretical basis for the promising treatment against cutaneus protothecosis.

Absence of synergistic effects between microplastics and copper ions on the spread of antibiotic resistance genes within aquatic bacteria at the community level.

Microplastics and copper ions (Cu2+) are favorable in accelerating the propagation of antibiotic resistance genes (ARGs) in the plastisphere, however, their combined effects on the ARG spread within the bacterial community of the natural environment were less understood. The influence of microplastic types and Cu2+ concentrations on the horizontal gene transfer (HGT) of ARGs mediated by RP4 plasmid within natural bacterial communities in aquatic environments was investigated. Both biodegradable polybutylene succinate (PBS) and non-biodegradable polyvinyl chloride (PVC) microplastics significantly enhanced the transfer of ARGs, with PBS showing a significant higher effect compared to PVC. Cu2+ also increased transconjugation rates at environmentally relevant concentrations (5 µg L-1), but higher levels (50 µg L-1) lead to decreased rates due to severe bacterial cell membrane damage. The transconjugation rates in the presence of both microplastics and Cu2+ were lower than the sum of their individual effects, indicating no synergistic effects between them on transconjugation. Proteobacteria dominated the composition of transconjugates for all the treatment. Transmission electron microscope images and reactive oxygen species production in bacterial cells indicated that the increased contact frequency due to extracellular polymeric substances, combined with enhanced membrane permeability induced by microplastics and Cu2+, accounted for the increasing transconjugation rates. The study provides valuable insight into the potential effects of microplastics and heavy metals on the spread of ARGs from donors to bacterial communities in natural environments.

Information of Growth Traits Is Helpful for Genetic Evaluation of Litter Size in Pigs.

Litter size is an important trait in pig production. But selection accuracy for this trait is relatively low, compared with production traits. This study, for the first time, investigated the improvement of genetic evaluation of reproduction traits such as litter size in pigs using data of production traits as an additional information source. The data of number of piglets born alive per litter (NBA), age at 100 kg of body weight (Age100), and lean meet percentage (LMP) in a Yorkshire population were analyzed, using either a single-trait model or the multitrait model that allows us to account for environmental correlation between reproduction and production traits in the situation that one individual has only one record for a production trait while multiple records for a reproduction trait. Accuracy of genetic evaluation using single-trait and multitrait models were assessed by model-based accuracy (Rm) and validation accuracy (Rv). Two validation scenarios were considered. One scenario (Valid_r1) was that the individuals did not have a record of NBA, but Age100 and LMP. The other (Valid_r2) was that the individuals did not have a record for all the three traits. The estimate of heritability was 0.279 for Age100, 0.371 for LMP, and 0.076 for NBA. Genetic correlation was 0.308 between Age100 and LMP, 0.369 between Age100 and NBA, and 0.022 between LMP and NBA. Compared with the single-trait model, the multitrait model including Age100 increased prediction accuracy for NBA by 3.6 percentage points in Rm and 5.9 percentage points in Rv for the scenario of Valid_r1. The increase was 1.8 percentage points in Rm and 3.8 percentage points in Rv for the scenario of Valid_r2. Age100 also gained in the multitrait model but was smaller than NBA. However, LMP did not benefit from a multitrait model and did not have a positive contribution to genetic evaluation for NBA. In addition, the multitrait model, in general, slightly reduced level bias but not dispersion bias of genetic evaluation. According to these results, it is recommended to predict breeding values using a multitrait model including growth and reproduction traits.

Application of Indoor Positioning Systems in Nursing Homes: Enhancing Resident Safety and Staff Efficiency.

Providing a safe and secure living environment for residents that is supported by a dedicated healthcare team is one of the core values of nursing homes. Nursing homes must protect residents from the risk of going missing, track quarantined residents and visitors to control the spread of infection, and maintain proactive nursing rounds. However, recruiting and retaining qualified caregivers and medical staff has long been a challenge. Therefore, using advanced technology to ensure the safety and security of residents is highly desirable. In this work, we first demonstrate the applicability of indoor tracking applications in a nursing home, such as resident and asset tracking, nursing assistant management, visitor tracking, infection control, and vital-sign monitoring. To monitor the locations of residents and staff, Bluetooth tags were used, providing real-time data for location tracking. We then conduct a series of quantitative analyses to illustrate how indoor tracking data can support the management of nursing homes, including characterizing residents' activities in daily living and assessing the performance and workload of nursing assistants. Finally, we use qualitative research to evaluate the acceptability of an indoor positioning system in the nursing home. The results show that the implemented indoor positioning applications can improve the quality of healthcare and working efficiency, thereby providing a safer and more secure living environment for residents.

Sodium alginate hydrogels co-encapsulated with cell free fat extract-loaded core-shell nanofibers and menstrual blood stem cells derived exosomes for acceleration of articular cartilage regeneration.

This study presents a novel scaffold system comprising sodium alginate hydrogels (SAh) co-encapsulated with cell-free fat extract (CEFFE)-loaded core-shell nanofibers (NFs) and menstrual blood stem cell-derived exosomes (EXOs). The scaffold integrates the regenerative potential of EXOs and CFFFE, offering a multifaceted strategy for promoting articular cartilage repair. Coaxially electrospun core-shell NFs exhibited successful encapsulation of CEFFE and seamless integration into the SAh matrix. Structural modifications induced by the incorporation of CEFFE-NFs enhanced hydrogel porosity, mechanical strength, and degradation kinetics, facilitating cell adhesion, proliferation, and tissue ingrowth. The release kinetics of growth factors from the composite scaffold demonstrated sustained and controlled release profiles, essential for optimal tissue regeneration. In vitro studies revealed high cell viability, enhanced chondrocyte proliferation, and migration in the presence of EXOs/CEFFE-NFs@SAh composite scaffolds. Additionally, in vivo experiments demonstrated significant cartilage regeneration, with the composite scaffold outperforming controls in promoting hyaline cartilage formation and defect bridging. Overall, this study underscores the potential of EXOs and CEFFE-NFs integrated into SAh matrices for enhancing chondrocyte viability, proliferation, migration, and ultimately, articular cartilage regeneration. Future research directions may focus on elucidating underlying mechanisms and conducting long-term in vivo studies to validate clinical applicability and scalability.

Room-Temperature Single-Molecule Infrared Imaging and Spectroscopy through Bond-Selective Fluorescence.

Infrared (IR) spectroscopy stands as a workhorse for exploring bond vibrations, offering a wealth of chemical insights across diverse frontiers. With increasing focus on the regime of single molecules, obtaining IR-sensitive information from individual molecules at room temperature would provide essential information about unknown molecular properties. Here, we leverage bond-selective fluorescence microscopy, facilitated by narrowband picosecond mid-IR and near-IR double-resonance excitation, for high-throughput mid-IR structural probing of single molecules. We robustly capture single-molecule images and analyze the combined polarization dependence, vibrational peaks, linewidths, and lifetimes of probe molecules with representative scaffolds. From bulk to single molecules, we find that vibrational lifetimes remain consistent, while linewidths are narrowed by approximately twofold and anisotropy becomes more pronounced. Additionally, unexpected peak shifts from single molecules were observed, attributed to the generation of new modes due to previously unexplored dimerization, supported by quantum chemistry calculations. These findings underscore the importance of infrared analysis on individual single molecules in ambient environments, offering molecular information crucial for functional imaging and the investigation of the fundamental properties and utilities of luminescent molecules.

Clinical characteristics and outcome analysis of pulmonary nocardiosis in southern China: a two-center retrospective study.

BACKGROUND: Pulmonary nocardiosis (PN) is a rare and opportunistic infection. This study aimed to analyze clinical, radiological, and microbiological features, treatment and outcome of PN in southern china. METHODS: Clinical, laboratory, imaging, treatment and outcome data of PN patients at two tertiary hospitals from January 1, 2018, to January 1, 2024 were collected. Factors associated with clinical outcomes were determined by multivariate logistic regression analysis. RESULTS: 67 PN patients including 53 with clinical improvement and 14 with treatment failure were enrolled. Bronchiectasis was the most common respiratory disease in patients with PN (31.3%). The major symptoms of PN were cough (89.6%) and sputum (79.1%). Lung nodules, bronchiectasis, consolidation, pleural involvement, mass, cavity, and lymph node enlargement were the frequent computed tomography findings of PN. Among the Nocardia species detected, N. farcinica was the most common pathogen. Neutrophil-to-lymphocyte ratio (OR = 1.052, p = 0.010), concurrent bacterial infection (OR = 7.706, p = 0.016), and the use of carbapenems (OR = 9.345, p = 0.023) were independently associated with poor prognosis in patients with PN. CONCLUSIONS: This study provides important insights into the clinical features of PN in southern china. neutrophil-to-lymphocyte ratio, concurrent bacterial infection, and the use of carbapenems were independently associated with poor prognosis in patients with PN.

Quantifying attention in children with intellectual and developmental disabilities through multicenter electrooculogram signal analysis.

In a multicenter case-control investigation, we assessed the efficacy of the Electrooculogram Signal Analysis (EOG-SA) method, which integrates attention-related visual evocation, electrooculography, and nonlinear analysis, for distinguishing between intellectual and developmental disabilities (IDD) and typical development (TD) in children. Analyzing 127 participants (63 IDD, 64 TD), we applied nonlinear dynamics for feature extraction. Results indicated EOG-SA's capability to distinguish IDD, with higher template thresholds and Correlation Dimension values correlating with clinical severity. The template threshold proved a robust indicator, with higher values denoting severe IDD. Discriminative metrics showed areas under the curve of 0.91 (template threshold) and 0.85/0.91 (D2), with sensitivities and specificities of 77.6%/95.9% and 93.5%/71.0%, respectively. EOG-SA emerges as a promising tool, offering interpretable neural biomarkers for early and nuanced diagnosis of IDD.