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Heterotopic ossification (HO), often arising in response to traumatic challenges, results from the aberrant osteochondral differentiation of mesenchymal stem cells (MSCs). Nevertheless, the impact of trauma‐induced inflammatory exposure on MSC fate determination remains ambiguous. In this study, the cellular diversity within inflammatory lesions is elucidated, comprising MSCs and several innate and adaptive immune cells. It is observed that quiescent MSCs transition into cycling MSCs, subsequently giving rise to chondrogenic (cMSC) and/or osteogenic (oMSC) lineages within the inflammatory microenvironment following muscle or tendon injuries, as revealed through single‐cell RNA sequencing (scRNA‐seq), spatial transcriptome and lineage tracing analysis. Moreover, these investigations demonstrate that neutrophils and natural killer (NK) cells enhance transition of quiescent MSCs into cycling MSCs, which is also controlled by M1 macrophages, a subpopulation of macrophages can also stimulate cMSC and oMSC production from cycling MSCs. Additionally, M2 macrophages, CD4+ and CD8+ T lymphocytes are found to promote chondrogenesis. Further analysis demonstrates that immune cells promotes the activation of signaling transducers and activators of transcription (STAT) pathway and phosphoinositide 3 (PI3K)/protein kinase B (AKT) pathway in MSC proliferation and osteochondral progenitors' production, respectively. These findings highlight the dynamics of MSC fate within the inflammatory lesion and unveil the molecular landscape of osteoimmunological interactions, which holds promise for advancing HO treatment. [ABSTRACT FROM AUTHOR]

A large‐scale outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) occurred in Shanghai, China, in early December 2022. To study the incidence and characteristics of otitis media with effusion (OME) complicating SARS‐CoV‐2, we collected 267 middle ear effusion (MEE) samples and 172 nasopharyngeal (NP) swabs from patients. The SARS‐CoV‐2 virus was detected by RT‐PCR targeting. The SARS‐CoV‐2 virus, angiotensin‐converting enzyme 2 (ACE2), and transmembrane serine protease 2 (TMPRSS2) expression in human samples was examined via immunofluorescence. During the COVID‐19 epidemic in 2022, the incidence of OME (3%) significantly increased compared to the same period from 2020 to 2022. Ear symptoms in patients with SARS‐CoV‐2 complicated by OME generally appeared late, even after a negative NP swab, an average of 9.33 ± 6.272 days after COVID‐19 infection. The SARS‐CoV‐2 virus was detected in MEE, which had a higher viral load than NP swabs. The insertion rate of tympanostomy tubes was not significantly higher than in OME patients in 2019–2022. Virus migration led to high viral loads in MEE despite negative NP swabs, indicating that OME lagged behind respiratory infections but had a favorable prognosis. Furthermore, middle ear tissue from adult humans coexpressed the ACE2 receptor for the SARS‐CoV‐2 virus and the TMPRSS2 cofactors required for virus entry. [ABSTRACT FROM AUTHOR]

Peptides and peptide aptamers have emerged as promising molecules for a wide range of biomedical applications due to their unique properties and versatile functionalities. The screening strategies for identifying peptides and peptide aptamers with desired properties are discussed, including high‐throughput screening, display screening technology, and in silico design approaches. The synthesis methods for the efficient production of peptides and peptide aptamers, such as solid‐phase peptide synthesis and biosynthesis technology, are described, along with their advantages and limitations. Moreover, various modification techniques are explored to enhance the stability, specificity, and pharmacokinetic properties of peptides and peptide aptamers. This includes chemical modifications, enzymatic modifications, biomodifications, genetic engineering modifications, and physical modifications. Furthermore, the review highlights the diverse biomedical applications of peptides and peptide aptamers, including targeted drug delivery, diagnostics, and therapeutic. This review provides valuable insights into the advancements in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers. A comprehensive understanding of these aspects will aid researchers in the development of novel peptide‐based therapeutics and diagnostic tools for various biomedical challenges. [ABSTRACT FROM AUTHOR]

Nanobodies (Nbs) are the variable domain of heavy‐chain antibodies derived from the blood of camelids or sharks. Nanobodies are the smallest antibody fragment with intact antigen‐binding ability. Compared to conventional antibodies, nanobodies have unique properties such as small size, excellent stability and solubility, low immunogenicity, ability to recognize hidden epitopes, high tissue penetration, and industrialized production. More excitingly, the camelid‐specific amino acid sequences in the framework are mutated to their human heavy‐chain variable domain equivalent, which is humanized, to a wide range of applications. These superior characteristics make nanobody an ideal alternative to conventional antibody, showing excellent prospects for various applications in structural biology, molecular imaging, disease diagnosis and therapy, agricultural products, and environmental chemicals detection. With the continuous updating of theories and the rapid development of technology, the screening and expression methods of nanobodies are increasingly mature. Consequently, several technologies to identify and express nanobodies have been established, and various use cases have been described. In this review, we summarize recent advances in the discovery and production of novel nanobodies, and their use in detection and diagnosis platforms. [ABSTRACT FROM AUTHOR]

Background: The inner ear organ is a delicate tissue consisting of hair cells (HCs) and supporting cells (SCs).The mammalian inner ear HCs are terminally differentiated cells that cannot spontaneously regenerate in adults. Epithelial non‐hair cells (ENHCs) in the utricle include HC progenitors and SCs, and the progenitors share similar characteristics with SCs in the neonatal inner ear. Methods: We applied single‐cell sequencing to whole mouse utricles from the neonatal period to adulthood, including samples from postnatal day (P)2, P7 and P30 mice. Furthermore, using transgenic mice and immunostaining, we traced the source of new HC generation. Results: We identified several sensory epithelial cell clusters and further found that new HCs arose mainly through differentiation from Sox9+ progenitor cells and that only a few cells were produced by mitotic proliferation in both neonatal and adult mouse utricles. In addition, we identified the proliferative cells using the marker UbcH10 and demonstrated that in adulthood the mitotically generated HCs were primarily found in the extrastriola. Moreover, we observed that not only Type II, but also Type I HCs could be regenerated by either mitotic cell proliferation or progenitor cell differentiation. Conclusions: Overall, our findings expand our understanding of ENHC cell fate and the characteristics of the vestibular organs in mammals over the course of development. [ABSTRACT FROM AUTHOR]

Automated, effective and efficient sleep‐stage monitoring and structure analysis is an essential enabling procedure for healthcare automation. Sleep diagnosis by polysomnography is a golden standard but expensive procedure involving huge effort from patients. There remain challenges for smart devices to precisely identify sleep stage and minimize intrusive effect on sleep progression. Herein, a novel noncontact sleep structure prediction system (NSSPS) using a single radar sensor is presented to analyze sleep structure without any tethered unit. The NSSPS is realized through training a convolutional recurrent neural network and neural conditional random fields using reflected radio frequency (RF) waves acquired by radar antennas. By capturing implicit temporal information in RF signals and transitions of sleep progression, high accuracy of sleep‐stage prediction is achieved and characteristics of sleep structure are extracted. The performance of the NSSPS is validated by transfer learning between radar signals with different frequency bands and crossvalidation among different subjects. Moreover, the NSSPS is demonstrated to estimate overnight parameters that are critical for sleep diagnosis. Benefiting from its low cost, convenient setup, and accurate prediction capability of sleep‐stage identification, the NSSPS can be widely deployed in "smart" homes and exploited to conduct daily sleep structure analysis. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To evaluate the diagnostic performance of short state homeobox 2 (SHOX2) promoter methylation as biomarker for lung cancer identification through aggregating the open published data.We did an electronic search in Pubmed, EMBASE, Ovid, Web of Science, Google Scholar, and the China National Knowledge Infrastructure (CNKI) to identify the publications related to SHOX2 promoter methylation and lung cancer. The diagnostic performance of sensitivity (SEN), specificity (SPE), odds ratio (DOR), and summary receiver operating characteristic (SROC) cure were aggregated by fixed or random effect model. Fagan's nomogram was used to investigate the post‐test diagnostic probability. Deek's funnel plot and line regression test was applied to evaluate the publication bias.In total, 18 clinical studies about SHOX2 promoter methylation and lung cancer were included in the meta‐analysis. The combined diagnostic SEN, SPE, DOR were 0.63 (95% CI = 0.54–0.70), 0.91 (95% CI = 0.87–0.94), and 16.84 (95% CI = 11.18–25.36) in random effect model respectively. The pooled area under the curve (AUC) of SROC was 0.88 (95% CI = 0.84–0.90). The post‐test probability of lung cancer was 88% and 29% when SHOX2 methylated and unmethylated in humoral components given a pre‐test probability of 50%. Deek's funnel plot and regression test indicated no publication bias (p = 0.62).SHOX2 promoter methylation in humoral components may be a potential biomarker for lung cancer diagnosis with relative high diagnostic specificity. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to quantitatively analysis the diagnostic performance of adenomatous polyposis coli (APC) gene promoter methylation in serum or sputum/bronchoalveolar lavage fluid (BLAF) as a biomarker for lung cancer identification through pooling of open published data. Methods: The relevant electronic MEDLINE, EMBASE, Ovid, web of science and CNKI databases were systematically searched to identify the studies related to APC gene promoter methylation for lung cancer diagnosis. Data of true positive (tp), false positive (fp), false negative (fn) and true negative (tn) were extracted from the publications included in the study. The pooled diagnostic sensitivity, specificity and area under summary receiver operating characteristic (SROC) curve (AUC‐SROC) of APC gene promoter methylation were calculated. Publication bias was evaluated by Begg's funnel plot and Egger's line regression test. Results: Fourteen studies associated with APC gene promoter methylation and lung cancer were identified in the databases and finally included in the meta‐analysis. The data was pooled using a random effect model due to significant statistical heterogeneity across the 14 studies (p < 0.05). Using the APC gene promoter methylation as a reference for lung cancer identification, the pooled diagnostic sensitivity and specificity were 0.43 (95% CI: 0.40–0.45), and 0.92 (95% CI: 0.90–0.95), respectively with combined diagnostic positive likelihood ratio (+LR) and negative likelihood ratio (−LR) of 7.15 (95% CI: 3.62–14.12) and 0.63 (95% CI: 0.57–0.71). The pooled diagnostic odds ratio (DOR) and AUC‐SROC of APC gene promoter methylation for lung cancer diagnosis were 9.84 (95% CI: 5.77–16.79) and 0.7, respectively. The Begg's funnel plot and Egger's line regression test both indicated statistical publication bias (t = 5.40, p < 0.05). Conclusions: APC gene promoter methylation in serum or sputum/BLAF is a potential biomarker for lung cancer diagnosis with high specificity. However, due to its low sensitivity, it may not be suitable for lung cancer screening in the general population. [ABSTRACT FROM AUTHOR]

Ferroptosis is a recently recognized form of non‐apoptotic cell death caused by an iron‐dependent accumulation of lipid hydroperoxides, which plays important roles in a wide spectrum of pathological conditions. The present study was aimed to investigate the impact of ferroptosis on cisplatin‐induced sensory hair cell damage. Cell viability was determined by Cell Counting Kit‐8 and lactase dehydrogenase assays. The reactive oxygen species (ROS) levels were evaluated by 2,7‐Dichlorodi‐hydrofluorescein diacetate (DCFH‐DA) and MitoSox‐Red staining. Mitochondrial membrane potential (MMP) was measured by tetramethylrhodamine methyl ester (TMRM) staining. Lipid peroxidation, intracellular and mitochondrial iron were detected by Liperfluo, C11‐BODIPY581/591, FerroOrange and Mito‐FerroGreen, respectively. We found that cisplatin treatment not only markedly augmented ROS accumulation, decreased the MMP, but increased lipid peroxidation and iron accumulation in House Ear Institute‐Organ of Corti 1 (HEI‐OC1) cells. Of note, treatment with the specific ferroptosis inhibitor ferrostatin‐1 could effectively abrogate the cisplatin‐induced toxicity and subsequent cell death. Specifically, the improvement of mitochondrial functions is important mechanisms for protective action of ferroptosis inhibitor against cisplatin‐induced damages in HEI‐OC1 cells. Moreover, inhibition of ferroptosis significantly protected murine cochlear hair cells against cisplatin damage. In addition, treatment murine cochlear hair cells with ferroptosis inducer, RSL3, significantly exacerbated cisplatin‐induced damage, which could be alleviated by ROS inhibitor N‐acetyl‐L‐cysteine. Collectively, our study indicated that ferroptosis inhibition could alleviate the cisplatin‐induced ototoxicity via inactivation of lipid peroxide radical and improvement of mitochondrial function in hair cells. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the correlation between calcium‐binding protein S100A8 and S100A9 expression in non‐small cell lung cancer (NSCLC) and patients’ clinical features. Methods: Fifty‐two NSCLC patients who underwent surgery at Zhejiang Hospital from February 2014 to January 2016 were included in this study. Calcium‐binding protein S100A8 and S100A9 expression patterns in cancer and para‐cancer tissues were examined by immunohistochemistry assay. The correlation between calcium‐binding protein S100A8 and S100A9 expression patterns and NSCLC patients’ clinical characteristics, including age, gender, tumor node metastasis stage, and pathology type, were evaluated. Results: S100A8 and S100A9 were generally expressed on the cytoplasm and nucleus of NSCLC cells, mainly located in the cytoplasm, stained with brown particles, and distributed evenly. The positive expression rates of S100A8 and S100A9 in cancer tissues were 71.2% and 76.9%, respectively, which were significantly higher than in para‐cancer tissues at 11.5% and 19.2%, respectively, with statistical significance (P < 0.05). S100A8 and S100A9 positive expression was associated with tumor differentiation degree (P < 0.05) but were not correlated with age, gender, smoking history, tumor diameter, pathology type, tumor node metastasis stage, or pleural effusion (Pall > 0.05). Conclusion: S100A8 and S100A9 positive expression in cancer tissues was significantly higher than in para‐cancer tissues and was correlated with tumor differentiation, which may be a potential marker for poor prognosis. [ABSTRACT FROM AUTHOR]

Scalable and routine integration of chemically exfoliated, graphene-based materials such as graphene oxide (GO) and reduced graphene oxide (rGO) into standard microelectronic fabrication is a tremendous technological challenge, blocking their advancement toward real applications. A unique approach for wafer-scale fabrication of rGO devices by a synergistic combination of chemically exfoliated GO with photolithography processing is realized. Using graphite powder as source material, a GO solution is produced in a newly optimized, low-temperature exfoliation and desalination protocol, resulting in high-quality GO and confirmed by various characterization techniques. As substrates, 4 in. Si/SiO2 or glass wafers were first silanized in a well-controlled, gas-phase procedure. Large-area GO thin films are then realized by standard spin-coating resulting in highly homogeneous, covalently bound layers of controllable thicknesses of 3-7 nm depending on the amount of spin-coatings. The robust thin films undergo routine photolithography for device fabrication, including reduction via thermal annealing into conductive rGO. The top-down fabricated rGO devices display high uniformity with electrical resistances varying within only one order of magnitude over wafer-scale and device yields as high as ≈93% on a wafer. The novel front-end-of-line GO integration protocol offers robust electrical performances for future implementation toward various sensor applications. [ABSTRACT FROM AUTHOR]

2D layered materials have gained tremendous research interests for gas sensing applications because of their ultrahigh theoretical specific surface areas and unique electronic properties, which are prone to be influenced by external factors. Here, using first principle calculations, the adsorption of several common gas molecules on graphene-like ZnO (g-ZnO) is systematically studied by taking the gas concentration, homolayer number, and heterolayers into considerations. The calculation results show that the adsorption energies of all the selected gas molecules are susceptible to the concentration and the homolayer number, and they incline to gradually increase with the decreasing of the gas concentration or they dramatically increase with the raising in g-ZnO layer number combined with elevated charge transfers. Besides, choosing graphene (MoS2) as a heterolayer material to stack with g-ZnO can enhance (weaken) the interaction with NH3 (NO2) while weakening (enhance) that of NO2 (NH3), thus facilitating the selectivity to some extent. Further, Hirshfeld charge analysis and visualization of the charge density differences between the layers reveal the different charge transfers and adsorption mechanisms before and after gas adsorption. The results indicate that g-ZnO and its homolayer and hetero-bilayer structures can be promising candidates as gas sensing materials and catalysis. [ABSTRACT FROM AUTHOR]

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BACKGROUND Animal models of neural tube defects (NTDs) have indicated roles for the Fzd3 gene and the planar cell polarity signaling pathway in convergent extension. We investigated the involvement of FZD3 in genetic and epigenetic mechanisms associated with human NTDs, especially spina bifida. We explored the effects of variants spanning the FZD3 gene in NTDs and examined the role of aberrant methylation of the FZD3 promoter on gene expression in brain tissue in spina bifida. METHODS Six FZD3 single nucleotide polymorphisms were genotyped using a MassARRAY system in tissue from 165 NTD fetuses and 152 controls. DNA methylation aberrations in the FZD3 promoter region were detected using a MassARRAY EpiTYPER (17 CpG units from −500 to −2400 bp from the transcription start site) in brain tissue from 77 spina bifida and 74 control fetuses. RESULTS None of the six single nucleotide polymorphisms evaluated were significantly associated with spina bifida, but the mean methylation level was significantly higher in spina bifida samples (13.70%) compared with control samples (10.91%) ( p = 0.001). In terms of specific sites, DNA methylation levels were significantly higher in the spina bifida samples at 14 of the 17 CpG units, which mostly included in R2 region. FZD3 mRNA expression was negatively correlated with methylation of the FZD3 promoter region, especially the R2 region (R = 0.970; p = 0.001) in HeLa cells. CONCLUSION The results of this study suggest that DNA methylation plays an important role in FZD3 gene expression regulation and may be associated with an increased risk of spina bifida. Birth Defects Research (Part A) 103:37-44, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Porous polycaprolactone/chitosan blend scaffolds with various compositional proportions were prepared using a particulate-leaching method. The pore parameters of resultant scaffolds were found to be mainly modulated by porogen. The compressive mechanical properties and hydrophilicity of scaffolds were examined by measuring their compressive modulus and stress strength as well as swelling index. Selected chondrocytes isolated from articular cartilage of knee joints of rabbits were seeded on these scaffolds, and further in vitro cultured for various periods. The growth and activity of seeded cells were estimated by counting numbers of cells proliferated on scaffolds and measuring the amounts of proteoglycans and type II collagen synthesized by the seeded cells. It was found that some scaffolds composed of proper component ratios and having appropriate pore parameters exhibited promising characteristics for the adhesion and proliferation of seeded cells while maintaining the phenotype and activity of the cells. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]