Differences in the prevalence of allergy and asthma among US children and adolescents during and before the COVID-19 pandemic.

BACKGROUND: The increasing prevalence of allergies and asthma has led to a growing global socioeconomic burden. Since the outbreak of the COVID-19 pandemic, the health and lifestyles of children and adolescents have changed dramatically. It's unclear how this shift impacted allergy and asthma, with limited studies addressing this question. We aim to explore the difference of the prevalence of allergies and asthma among US children and adolescents during and before the COVID-19 pandemic using a nationally representative sample of US children and adolescents. METHODS: This cross-sectional study included 31,503 participants in the National Health Interview Survey (NHIS) between 2018 and 2021. Allergies and asthma were defined on an affirmative response in the questionnaire by a parent or guardian. Chi-square tests were used to compare baseline characteristics with allergies and asthma for categorical variables. Differences in prevalence during and before the COVID-19 pandemic were estimated with weighted logistic regression, adjusting for demographic factors. Interaction analyses explored variations across strata. RESULTS: In US children and adolescents aged 0 to 17, prevalence of any allergy was 26.1% (95% CI, 24.8%- 27.4%) in 2018 and 27.1% (95% CI, 25.9%- 28.2%) in 2021. Thereinto, in 2018, prevalence of respiratory allergies, food allergies and skin allergies were 14.0% (95% CI, 13.1%- 15.0%), 6.5% (95% CI, 5.8%- 7.1%) and 12.6% (95% CI, 11.6%- 13.5%), respectively, and in 2021, 18.8% (95% CI, 17.8%- 19.9%), 5.8% (95% CI, 5.2%- 6.4%) and 10.7% (95% CI, 9.9%- 11.5%), respectively. And prevalence of asthma was 11.1% (95% CI, 10.5%- 11.7%) in 2018-2019 and 9.8% (95% CI, 9.2%- 10.4%) in 2020-2021. Prevalence of respiratory allergies, skin allergies and asthma during and before the COVID-19 pandemic in children and adolescents had statistically significant differences. The differences persisted after adjusting for demographic and socioeconomic variables. CONCLUSION: Prevalence of respiratory allergies increased and the prevalence of both skin allergies and asthma decreased among US children and adolescents during the COVID-19 pandemic compared with the pre-COVID-19 pandemic. Further research is required to explore the association between allergic diseases and the pandemic, with a particular emphasis on the impact of lifestyle changes resulting from measures to prevent COVID-19 infection.

TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models.

Therapeutics for eradicating hepatitis B virus (HBV) infection are still limited and current nucleos(t)ide analogs (NAs) and interferon are effective in controlling viral replication and improving liver health, but they cannot completely eradicate the hepatitis B virus and only a very small number of patients are cured of it. The TCR-like antibodies recognizing viral peptides presented on human leukocyte antigens (HLA) provide possible tools for targeting and eliminating HBV-infected hepatocytes. Here, we generated three TCR-like antibodies targeting three different HLA-A2.1-presented peptides derived from HBV core and surface proteins. Bispecific antibodies (BsAbs) were developed by fuzing variable fragments of these TCR-like mAbs with an anti-CD3ϵ antibody. Our data demonstrate that the BsAbs could act as T cell engagers, effectively redirecting and activating T cells to target HBV-infected hepatocytes in vitro and in vivo. In HBV-persistent mice expressing human HLA-A2.1, two infusions of BsAbs induced marked and sustained suppression in serum HBsAg levels and also reduced the numbers of HBV-positive hepatocytes. These findings highlighted the therapeutic potential of TCR-like BsAbs as a new strategy to cure hepatitis B.

Mitochondria-targeted sonodynamic modulation of neuroinflammation to protect against myocardial ischemia‒reperfusion injury.

Sympathetic hyperactivation and inflammatory responses are the main causes of myocardial ischemia‒reperfusion (I/R) injury and myocardial I/R-related ventricular arrhythmias (VAs). Previous studies have demonstrated that light-emitting diodes (LEDs) could modulate post-I/R neuroinflammation, thus providing protection against myocardial I/R injury. Nevertheless, further applications of LEDs are constrained due to the low penetration depth (<1 cm) and potential phototoxicity. Low-intensity focused ultrasound (LIFU), an emerging noninvasive neuromodulation strategy with deeper penetration depth (∼10 cm), has been confirmed to modulate sympathetic nerve activity and inflammatory responses. Sonodynamic therapy (SDT), which combines LIFU with sonosensitizers, confers additional advantages, including superior therapeutic efficacy, precise localization of neuronal modulation and negligible side effects. Herein, LIFU and SDT were introduced to modulate post-myocardial I/R neuroinflammation to protect against myocardial I/R injury. The results indicated that LIFU and SDT inhibited sympathetic neural activity, suppressed the activation of astrocytes and microglia, and promoted microglial polarization towards the M2 phenotype, thereby attenuating myocardial I/R injury and preventing I/R-related malignant VAs. These insights suggest that LIFU and SDT inspire a noninvasive and efficient neuroinflammatory modulation strategy with great clinical translation potential thus benefiting more patients with myocardial I/R in the future. STATEMENT OF SIGNIFICANCE: Myocardial ischemia-reperfusion (I/R) may cause I/R injury and I/R-induced ventricular arrhythmias. Sympathetic hyperactivation and inflammatory response play an adverse effect in myocardial I/R injury. Previous studies have shown that light emitting diode (LED) can regulate I/R-induced neuroinflammation, thus playing a myocardial protective role. However, due to the low penetration depth and potential phototoxicity of LED, it is difficult to achieve clinical translation. Herein, we introduced sonodynamic modulation of neuroinflammation to protect against myocardial I/R injury, based on mitochondria-targeted nanosonosensitizers (CCNU980 NPs). We demonstrated that sonodynamic modulation could promote microglial autophagy, thereby preventing myocardial I/R injury and I/R-induced ventricular arrhythmias. This is the first example of sonodynamic modulation of myocardial I/R-induced neuroinflammation, providing a novel strategy for clinical translation.

Morphological manifestation of tuberculous pleurisy in children under medical thoracoscope and diagnostic value.

OBJECTIVE: Our study analyzed the main manifestations of tuberculous pleurisy (TBP) in children under medical thoracoscopy (MT). This article aimed to explore the clinical application value of MT in the diagnosis and treatment of TBP in children. METHODS: In our study, we selected 23 TBP patients diagnosed in our hospital. We analyzed the clinical data and thoracoscopic morphology of these patients. At the same time, we also observed the pathological manifestations, acid-fast staining, and treatment effects of the patient's diseased tissue under MT. RESULTS: The MT clinical findings of TBP patients include pleural hyperemia and edema, miliary nodules, scattered or more white nodules, simple pleural adhesion, wrapped pleural effusion, massive cellulose exudation, yellow-white caseous necrosis, pleural hyperplasia and hyperplasia, and mixed pleural necrosis. The positive rate of pleural biopsy was 73.91% and that of acid-fast staining was 34.78%. The main pathologic types of these patients were tuberculous granulomatous lesions (16 cases), caseous necrosis (5 cases), and fibrinous exudative, multinucleated giant cell and other inflammatory cell infiltration lesions (13 cases). The average time of diagnosis of the 23 patients was 8.32 days (5.0-16.0 days), and they were transferred to specialized hospitals for treatment after diagnosis. The mean time of chest drainage was 3.0-5.0 days after treatment. The average time for their body temperature to return to normal was 3.31 days (2.0-5.0 days). CONCLUSION: Thoracoscopic lesions of TBP in children are varied. The use of MT is not only helpful for the early diagnosis and treatment of TBP. It also protects and improves lung function. Therefore, the use of MT has high clinical value.

Oral Saccharomyces cerevisiae-Guided Enzyme Prodrug Therapy Combined with Immunotherapy for the Treatment of Orthotopic Colorectal Cancer.

Colorectal cancer (CRC) is a major global health concern, and the development of effective treatment strategies is crucial. Enzyme prodrug therapy (EPT) shows promise in combating tumors but faces challenges in achieving sustained expression of therapeutic enzymes and optimal biological distribution. To address these issues, a fungi-triggered in situ chemotherapeutics generator (named as SC@CS@5-FC) was constructed via oral delivery of a prodrug (5-fluorocytosine, 5-FC) for the treatment of orthotopic colorectal tumor. When SC@CS@5-FC targets the tumor through tropism by Saccharomyces cerevisiae (SC), the chemotherapeutic generator could be degraded under abundant hyaluronidase (HAase) in the tumor microenvironment by an enzyme-responsive gate to release prodrug (5-FC). And nontoxic 5-FC was catalyzed to toxic chemotherapy drug 5-fluorouracil (5-FU) by cytosine deaminase (CD) of SC. Meanwhile, SC and zinc-coordinated chitosan nanoparticles could be used as immune adjuvants to activate antigen-presenting cells and further enhance the therapeutic effect. Our results demonstrated that SC@CS@5-FC could effectively inhibit tumor growth and prolong mouse survival in an orthotopic colorectal cancer model. This work utilizes living SC as a dynamotor and positioning system for the chemotherapeutic generator SC@CS@5-FC, providing a strategy for oral enzyme prodrug therapy for the treatment of orthotopic colorectal.

Manipulation of Exchange Bias in Two-Dimensional van der Waals Ferromagnet Near Room Temperature.

As a host for exchange bias (EB), van der Waals (vdW) magnetic materials have exhibited intriguing and distinct functionalities from conventional magnetic materials. The EB in most vdW systems is far below room temperature, which poses a challenge for practical applications. Here, by using Kerr microscopy, we demonstrate a record-high blocking temperature that approaches room temperature and a huge positive EB field that nears 2 kOe at 100 K in naturally oxidized two-dimensional (2D) vdW ferromagnetic Fe3GaTe2 nanoflakes. Moreover, we realized a reversible manipulation of both the presence/absence and positive/negative signs of EB via a training magnetic field without multiple field cooling processes. Thus, our study clearly reveals the robust, sizable, and sign-tunable EB in vdW magnetic materials up to near room temperature, thereby establishing Fe3GaTe2 as an emerging room-temperature-operating vdW material and paving the way for designing practical 2D spintronic devices.

Triplet-aware graph neural networks for factorized multi-modal knowledge graph entity alignment.

Multi-Modal Entity Alignment (MMEA), aiming to discover matching entity pairs on two multi-modal knowledge graphs (MMKGs), is an essential task in knowledge graph fusion. Through mining feature information of MMKGs, entities are aligned to tackle the issue that an MMKG is incapable of effective integration. The recent attempt at neighbors and attribute fusion mainly focuses on aggregating multi-modal attributes, neglecting the structure effect with multi-modal attributes for entity alignment. This paper proposes an innovative approach, namely TriFac, to exploit embedding refinement for factorizing the original multi-modal knowledge graphs through a two-stage MMKG factorization. Notably, we propose triplet-aware graph neural networks to aggregate multi-relational features. We propose multi-modal fusion for aggregating multiple features and design three novel metrics to measure knowledge graph factorization performance on the unified factorized latent space. Empirical results indicate the effectiveness of TriFac, surpassing previous state-of-the-art models on two MMEA datasets and a power system dataset.

Light-induced manipulation of ultra-low surface tension droplets on stable quasi-liquid surfaces.

HYPOTHESIS: Perfluorocarbon is commonly used as a coolant, chemical reaction carrier solvent, medical anti-hypoxic agents and blood substitutes. The realization of non-contact complex manipulation of perfluorocarbon liquids is urgently needed in human life and industrial production. However, most liquid-repellent interfaces are ineffective for the transport of ultra-low surface tension perfluorocarbon liquids, and struggle to maintain good durability due to unstable air or oil cushions in the surface. Therefore, preparing surfaces for stable non-contact complex manipulation of ultra-low surface tension droplets remains a challenge. EXPERIMENTS: In this paper, a novel solution, a photothermal responsive droplet manipulation surface based on polydimethylsiloxane brushes, has been reported. On this surface, droplets with different surface tensions (as low as 10 mN/m) can be efficiently manipulated through induced near-infrared light. Notably, this surface maintains its effectiveness after exposure to extreme anthropogenic conditions. FINDINGS: The interface effect between perfluorocarbon droplets and polydimethylsiloxane brushes by near-infrared light-induced was investigated in detail. In addition, ultra-low surface tension droplets demonstrate the ability to transport solid particles. The conductive droplets exhibit sophisticated manipulation realizing the controlled switching of smart circuits. This research opens up new possibilities for advancing the capabilities and adaptability of ultralow surface tension droplets in a range of applications.

Selective extraction of genomic DNA from leopard cat (Prionailurus bengalensis), hairy-crowned deer (Elaphodus cephalophus) and muntjac (Muntiacus reevesi) using hydrophobic magnetic deep eutectic solvents.

Wild animals, as a vital component of our natural world, serve a crucial role in preserving ecological equilibrium and biodiversity. By delving into the genetic constitution of wild animal populations, the evolutionary history, genetic diversity, and adaptation mechanisms could be explored, thereby informing conservation strategies and safeguarding the future of these species. In order to study the genetic information of wild animals, it is necessary to extract high purity and high concentration of wild animal genomic DNA. In this work, a hydrophobic magnetic deep eutectic solvent (HMDES) based vortexed extraction was developed for the extraction of genomic DNA from leopard cat (Prionailurus bengalensis), hairy-crowned deer (Elaphodus cephalophus) and muntjac (Muntiacus reevesi) muscle tissue, respectively. Extraction conditions like the pH value, extraction time, temperature and the amount of HMDES used were optimized by single-factor experiments. Under the optimized condition, genomic DNA could be selectively extracted from the three animal tissues. The limits of detection (LOD) and limits of quantification (LOQ) of the proposed method were 2.86 ng/µL and 8.66 ng/µL, respectively. Meanwhile, the relative standard deviation (RSD) of the method precision and repeatability were 1.64 % and 5.57 % at 20 ng/µL, showing the method has good precision and repeatability. After extraction, the DNA extracted into the HMDES droplets can be quickly recovered and the HMDES can be recycled and reused. The method proposed is a fast, environmental-friendly and high efficient extraction strategy for purification and enrichment of genomic DNA from leopard cat, hairy-crowned deer and muntjac tissues.

GDF11 evokes lung injury, inflammation, and fibrosis in mice through the ALK5-Smad2/3 signaling pathway.

Growth differentiation factor 11 (GDF11) belongs to the transforming growth factor-ß (TGF-ß) superfamily and participates in various pathophysiological processes. Initially, GDF11 was suggested to act as a rejuvenator by improving age-related phenotypes of the heart, brain, and skeletal muscle in aged mice. However, recent studies demonstrate that GDF11 also serves as an adverse risk factor for human frailty and diseases. However, the role of GDF11 in pulmonary fibrosis (PF) remains unclear. In this study, we explored the role and signaling mechanisms of GDF11 in PF. We discovered that GDF11 expression was markedly upregulated in fibrotic lung tissues of both humans and mice. Intratracheal administration of commercial recombinant GDF11 caused lung injury, inflammation, and fibrogenesis in mice. Furthermore, adenovirus-mediated secretory expression of mature GDF11 was exacerbated, whereas full-length GDF11 or the GDF11 propeptide (GDF111-298) alleviated bleomycin-induced PF in mice. In vitro experiments demonstrated that GDF11 suppressed the growth of alveolar and bronchial epithelial cells (A549 and BEAS-2B) and pulmonary microvascular endothelial cells (HPMVEC), promoted fibroblast activation, and induced epithelial/endothelial-mesenchymal transition (EMT/EndoMT). These effects corresponded to the phosphorylation of Smad2/3, and blocking ALK5-Smad2/3 signaling abolished the in vivo and in vitro effects of GDF11. In conclusion, our findings provide evidence that GDF11 acts as a potent injurious, pro-inflammatory, and pro-fibrotic factor in the lungs via the ALK5-Smad2/3 pathway.

Quality evaluation of Qiangli Tianma Duzhong (QLTMDZ) employing UHPLC-MS: A multivariate statistical analysis across multiple dosage forms and manufacturers.

Traditional Chinese medicine (TCM) and its preparations have become increasingly popular in recent years. Nonetheless, due to the high complexity of the compounds in Traditional Chinese Patent Medicine (TCPM), the quality differences between different dosage forms and products from various manufacturers pose numerous challenges and difficulties in quality evaluation. The Qiangli Tianma Duzhong (QLTMDZ) prescription, comprising twelve TCM, is widely used in China. Despite its prevalence, current research on QLTMDZ is limited and lacks in-depth and systematic analysis of the chemical composition of the prescription. In this study, a comprehensive strategy was proposed for characterizing the chemical profile of QLTMDZ based on UHPLC-Q-TOF-MS. A total of 122 compounds were identified in QLTMDZ under both positive and negative ion modes. Subsequently, multivariate statistical methods such as principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were conducted in the MS-DIAL software to further elucidate quality differences among 55 batches of QLTMDZ samples from seven manufacturers. Lastly, multiple reaction monitoring (MRM) mode was utilized in conjunction with UHPLC-QQQ-MS, for the precise quantification of the identified 24 compounds within the QLTMDZ preparation and providing supplementary information in quality evaluation. The established analytical method in this study is sensitive and efficient, enabling qualitative and quantitative analysis of the chemical constituents within QLTMDZ. The application of multivariate statistical analyses effectively discriminates samples based on different dosage forms and manufacturers, thereby providing new research directions and scientific support for further studies on the quality control of the prescription.

Metal Ion Modulated Electron Transfer in Metalloviologen Compounds: Photochromism and Differentiable Amine Detection.

Different types of electron transfers (ETs) underlie the versatile use of various solid viologen-derived compounds, which is still insufficiently understood and difficult to control. Here, we demonstrate an effective strategy for modulating the key ET process in crystalline metalloviologen compounds (MVCs). By adjusting the coordinated transition metal ions bearing different electronic structures (e.g., d5, d7, d10), three MVCs (i.e., Mn-1, Co-2, and Cd-3) with highly consistent coordination environments have been synthesized successfully. Surprisingly, whether the photochromism (energy-induced ET mechanism) or the specific analyte recognition (molecule-induced ET mechanism), compound Cd-3 exhibits obvious photochromic behavior and differential dimethylamine detection. Combined detailed structural analysis with theoretical calculations, such unique ion-dependent properties, were correlated to the fine modulation of the electron density of the bipyridinium cores by metal ions. Additionally, thanks to the delicate recognition of dimethylamine vapor, a convenient test strip Cd-3-PAN was prepared as a sensitive biogenic amine sensor for evaluating the real-time freshness of seafood.

Mechanical stress-induced autophagy is cytoskeleton dependent.

The cytoskeleton is essential for mechanical signal transduction and autophagy. However, few studies have directly demonstrated the contribution of the cytoskeleton to mechanical stress-induced autophagy. We explored the role of the cytoskeleton in response to compressive force-induced autophagy in human cell lines. Inhibition and activation of cytoskeletal polymerization using small chemical molecules revealed that cytoskeletal microfilaments are required for changes in the number of autophagosomes, whereas microtubules play an auxiliary role in mechanical stress-induced autophagy. The intrinsic mechanical properties and special intracellular distribution of microfilaments may account for a large proportion of compression-induced autophagy. Our experimental data support that microfilaments are core components of mechanotransduction signals.

Promoted Stability and Reaction Kinetics in Ni-Rich Cathodes via Mechanical Fusing Multifunctional LiZr2(PO4)3 Nanocrystals for High Mass Loading All-Solid-State Lithium Batteries.

Sulfide all-solid-state lithium battery (ASSLB) with nickel-rich layered oxide as the cathode is promising for next-generation energy storage system. However, the Li+ transport dynamic and stability in ASSLB are hindered by the structural mismatches and the instabilities especially at the oxide cathode/sulfide solid electrolyte (SE) interface. In this work, we have demonstrated a simple and highly effective solid-state mechanofusion method (1500 rpm for 10 min) to combine lithium conductive NASICON-type LiZr2(PO4)3 nanocrystals (∼20 nm) uniformly and compactly onto the surface of the single crystallized LiNi0.8Co0.1Mn0.1O2, which can also attractively achieve Zr4+ doping in NCM811 and oxygen vacancies in the LZPO coating without solvent and annealing. Benefiting from the alleviated interface mismatches, sufficient Li+ ion flux through the LZPO coating, promoted structural stabilities for both NCM811 and sulfide SE, strong electronic coupling effect between the LZPO and NCM811, and enlarged (003) d-spacing with enriched Li+ migration channels in NCM811, the obtained LZPO-NCM811 exhibits superior stability (185 mAh/g at 0.1C for 200 cycles) and rate performance (105 mAh/g at 1C for 1300 cycles) with high mass loading of 27 mgNCM/cm2 in sulfide ASSLB. Even with a pronounced 54 mgNCM/cm2, LZPO-NCM811 manifests a high areal capacity of 9.85 mAh/cm2. The convenient and highly effective interface engineering strategy paves the way to large-scale production of various coated cathode materials with synergistic effects for high performance ASSLBs.

From onset to blindness: a comprehensive analysis of RPGR-associated X-linked retinopathy in a large cohort in China.

BACKGROUND: Variants in the RPGR are the leading cause of X-linked retinopathies (XLRPs). Further in-depth investigation is needed to understand the natural history. METHODS: Review of all case records, molecular genetic testing results, best-corrected visual acuity (BCVA), retinal imaging data (including fundus autofluorescence imaging and optical coherence tomography (OCT)), static visual field (VF) assessments and full-field electroretinogram. RESULTS: Genetic testing was conducted on 104 male patients from 89 family pedigrees, identifying 22 novel variants and 1 de novo variant. The initial symptoms appeared in 78.2% of patients at a median age of 5 years. BCVA declined at a mean rate of 0.02 (IQR, 0-0.04) logarithm of the minimum angle of resolution per year, with a gradual, non-linear decrease over the first 40 years. Autofluorescence imaging revealed macular atrophy at a median age of 36.1 (IQR, 29.9-43.2) years. Patients experienced blindness at a median age of 42.5 (IQR, 32.9-45.2) years according to WHO visual impairment categories. OCT analysis showed a mean ellipsoid zone narrowing rate of 23.3 (IQR, -1.04-22.29) µm/month, with an accelerated reduction in the first 40 years (p<0.01). The median age at which ERG no longer detected a waveform was 26.5 (IQR, 20.5-32.8) years. Comparison by variant location indicated faster progression in patients with exon 1-14 variants during the initial two decades, while those with ORF15 variants showed accelerated progression from the third decade. CONCLUSIONS: We provide a foundation for determining the treatment window and an objective basis for evaluating the therapeutic efficacy of gene therapy for XLRP.

Spatial distribution pattern of mustelids in the eastern edge of the Qinghai-Tibet Plateau.

Evolutionary theory predicts that the species of an evolutionarily successful taxon would not overlap in spatial distribution. To test the prediction, we document our research on the spatial associations of mustelids, an evolutionarily successful group of order Carnivore, using infrared camera trap data on species distribution collected from the national nature reserves (NNRs) of Liancheng, Wolong, Tangjiahe and Heizhugou in China in 2017-2021. Data showed seven mustelid species occurring in the study area, including Arctonyx collaris, Meles leucurus, Martes foina, Martes flavigula, Mustela altaica, Mustela nivalis and Mustela sibirica. Following Ricklef's definition of biological community, we identified five networks of species associations. The mustelids occurred in the networks. Species from the same genus, such as M. foina and M. flavigula, stayed in different networks to avoid competition owing to similar feeding habits or habitat preferences. Species with different feeding habits or habitat preferences either occurred in different networks, such as M. altaica and M. flavigula, or coexisted in the same networks but avoided direct spatial associations, such as M. foina and A. collaris. Asymmetrical associations were found between different genera, such as M. foina and M. altaica, or between different subfamilies, such as M. flavigula and A. collaris. These associations may be attributed to interspecific killing or seed dispersal. However, these associations accounted for only a small proportion and would not impact the species diversity of Mustelidae. It is thus concluded that the prediction is supported by our research findings and that spatial avoidance may be the biogeographic strategy of maintaining the species diversity of the family. We also found that the well protection of the mustelids may benefit the overall biodiversity conservation in Heizhugou, an NNR that has experienced severe deforestation.

Engineered exosomes transporting the lncRNA, SVIL-AS1, inhibit the progression of lung cancer via targeting miR-21-5p.

In this study, we constructed engineered exosomes carrying the long non-coding RNA (lncRNA) SVIL-AS1 (SVIL-AS1 Exos), and explored its role and mechanism in lung cancer. After the construction of SVIL-AS1 Exos, their physicochemical characteristics were identified. Then, their function and effect in three different cell lines, A549, HeLa, and HepG2, were detected using western blot, the quantitative reverse transcriptase polymerase chain reaction, flow cytometry, 5-ethynyl-2'-deoxyuridine, and Cell Counting Kit-8 experiments. Finally, a mouse xenograft model was constructed to analyze tumor growth and explore the in vivo utility of SVIL-AS1 Exos using hematoxylin and eosin staining, immunohistochemistry, and the TdT-mediated dUTP nick end labeling assay. The results demonstrated that SVIL-AS1 Exos preferentially targeted A549 lung cancer cells over HeLa and HepG2 cells. SVIL-AS1 Exos promoted apoptosis and inhibited A549 cell proliferation by elevating expression of the lncRNA, SVIL-AS1. In vivo, SVIL-AS1 Exos effectively inhibited the growth of lung cancer A549 cells. Furthermore, SVIL-AS1 Exos suppressed the expression of miR-21-5p and upregulated the expression of caspase-9, indicating that SVIL-AS1 may regulate the development of lung cancer through the miR-21-5p/caspase-9 pathway. In conclusion, the engineered SVIL-AS1 Exos targeted lung cancer cells to inhibit the expression of miR-21-5p, upregulate the expression of caspase-9, and inhibit the development of lung cancer.

CD38 deficiency prevents diabetic nephropathy by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Diabetic nephropathy (DN) is one of the most common complications of diabetes. Our previous study showed that CD38 knockout (CD38KO) mice had protective effects on many diseases. However, the roles and mechanisms of CD38 in DN remain unknown. Here, DN mice were generated by HFD feeding plus streptozotocin (STZ) injection in male CD38KO and CD38flox mice. Mesangial cells (SV40 MES 13 cells) were used to mimic the injury of DN with palmitic acid (PA) treatment in vitro. Our results showed that CD38 expression was significantly increased in kidney of diabetic CD38flox mice and SV40 MES 13 cells treated with PA. CD38KO mice were significantly resistant to diabetes-induced renal injury. Moreover, CD38 deficiency markedly decreased HFD/STZ-induced lipid accumulation, fibrosis and oxidative stress in kidney tissue. In contrast, overexpression of CD38 aggravated PA-induced lipid accumulation and oxidative stress. CD38 deficiency increased expression of SIRT3, while overexpression of CD38 decreased its expression. More importantly, 3-TYP, an inhibitor of SIRT3, significantly enhanced PA-induced lipid accumulation and oxidative stress in CD38 overexpressing cell lines. In conclusion, our results demonstrated that CD38 deficiency prevented DN by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Impact of uniaxial cyclic stretching on matrix-associated endothelial cell responses.

Uniaxial cyclic stretching plays a pivotal role in the fields of tissue engineering and regenerative medicine, influencing cell behaviors and functionality based on physical properties, including matrix morphology and mechanical stimuli. This study delves into the response of endothelial cells to uniaxial cyclic strain within the geometric constraints of micro-nano fibers. Various structural scaffold forms of poly(l-lactide-co-caprolactone) (PLCL), such as flat membranes, randomly oriented fiber membranes, and aligned fiber membranes, were fabricated through solvent casting and electrospinning methods. Our investigation focuses on the morphological variation of endothelial cells under diverse geometric constraints and the mechanical-dependent release of nitric oxide (NO) on oriented fibrous membranes. Our results indicate that while uniaxial cyclic stretching promotes endothelial cell spreading, the anisotropy of the matrix morphology remains the primary driving factor for cell alignment. Additionally, uniaxial cyclic stretching significantly enhances NO release, with a notably stronger effect correlated to the increasing strain amplitude. Importantly, this study reveals that uniaxial cyclic stretching enhances the mRNA expression of key proteins, including talin, vinculin, rac, and nitric oxide synthase (eNOS).