Molecular Stratification and Treatment Monitoring of Lung Cancer Using a Small Extracellular Vesicle-Activated Nanocavity Architecture.

Development of molecular diagnostics for lung cancer stratification and monitoring is crucial for the rational planning and timely adjustment of treatments to improve clinical outcomes. In this regard, we propose a nanocavity architecture to sensitively profile the protein signature on small extracellular vesicles (sEVs) to enable accurate, noninvasive staging and treatment monitoring of lung cancer. The nanocavity architecture is formed by molecular recognition through the binding of sEVs with the nanobox-based core-shell surface-enhanced Raman scattering (SERS) barcodes and mirrorlike, asymmetric gold microelectrodes. By imposing an alternating current on the gold microelectrodes, a nanofluidic shear force was stimulated that supported the binding of sEVs and the efficient assembly of the nanoboxes. The binding of sEVs further induced a nanocavity between the nanobox and the gold microelectrode that significantly amplified the electromagnetic field to enable the simultaneous enhancement of Raman signals from four SERS barcodes and generate patient-specific molecular sEV signatures. Importantly, evaluated on a cohort of clinical samples (n = 76) on the nanocavity architecture, the acquired patient-specific sEV molecular signatures achieved accurate identification, stratification, and treatment monitoring of lung cancer patients, highlighting its potential for transition to clinical utility.

Single-cell transcriptomic landscape and the microenvironment of normal adjacent tissues in hypopharyngeal carcinoma.

BACKGROUND: The cellular origin of hypopharyngeal diseases is crucial for further diagnosis and treatment, and the microenvironment in tissues may also be associated with specific cell types at the same time. Normal adjacent tissues (NATs) of hypopharyngeal carcinoma differ from non-tumor-bearing tissues, and can influenced by the tumor. However, the heterogeneity in kinds of disease samples remains little known, and the transcriptomic profile about biological information associated with disease occurrence and clinical outcome contained in it has yet to be fully evaluated. For these reasons, we should quickly investigate the taxonomic and transcriptomic information of NATs in human hypopharynx. RESULTS: Single-cell suspensions of normal adjacent tissues (NATs) of hypopharyngeal carcinoma were obtained and single-cell RNA sequencing (scRNA-seq) was performed. We present scRNA-seq data from 39,315 high-quality cells in the hypopharyngeal from five human donors, nine clusters of normal adjacent human hypopharyngeal cells were presented, including epithelial cells, endothelial cells (ECs), mononuclear phagocyte system cells (MPs), fibroblasts, T cells, plasma cells, B cells, mural cells and mast cells. Nonimmune components in the microenvironment, including epithelial cells, endothelial cells, fibroblasts and the subpopulations of them were performed. CONCLUSIONS: Our data provide a solid basis for the study of single-cell landscape in human normal adjacent hypopharyngeal tissues biology and related diseases.

Exogenous hydrogen sulfide prevents necroptosis by inhibiting p38MAPK pathway activation in JEG-3 trophoblast cells: A role in preeclampsia.

Setting 7 subsection in abstract Objectives: Necroptosis, a form of programmed cell death, can occur in the placenta of patients with preeclampsia (PE). Hydrogen sulfide (H2S) can inhibit necroptosis of human umbilical vein endothelial cells under the high-glucose-induced injury. Whether H2S can protect trophoblasts against necroptosis underlying PE has not been elucidated. This study was aimed to explore the protective role of H2S in trophoblast cells against necroptosis underlying PE. DESIGN: This is an in vitro experimental study. PARTICIPANTS: A total of 10 pregnant women with severe preeclampsia (PE) and 10 matched control normotensive pregnant women were included. The placenta tissues were extracted from participators. The human JEG-3 trophoblasts were commercially available. METHODS: The expression and localization of necrotic proteins were assayed in human placenta samples and the effect of necrotic cell death on the proliferation and apoptosis of human JEG-3 trophoblasts was evaluated. The component expressions of inflammatory cytokine and p38MAPK signaling pathway were measured in samples pretreated with or without NaHS (H2S donor) and SB203580 (p38 inhibitor). RESULTS: RIPA1, RIPA3, and p-p38 levels were significantly higher in PE placental tissue, whereas cystathionine-ß-synthase expression was decreased. In JEG-3 trophoblasts, necroptosis increased apoptotic cell numbers, suppressed cell proliferation, increased inflammatory cytokine expression, and increased p38MAPK activation, which can be prevented by NaHS. LIMITATIONS: In the present study, we did not provide sufficient evidence that necroptosis was a part of the pathogenesis of preeclampsia. CONCLUSIONS: we proposed the putative role of necroptosis in early-onset PE, reflected by the blockage of caspase-8/3 and increased expression of RIPA1, and RIPA3 in PE placenta tissues. Furthermore, we demonstrated that exogenous H2S protected cytotrophoblasts against CER-induced necroptosis via the p38MAPK pathway.

Network Pharmacology and Experimental Verification of Si Shen Decoction Regulating FABP4/PPARγ/NFκB Pathway in the Treatment of Collagen-induced Arthritis.

AIM: This study aimed to investigate the mechanism of SSD in rats with Collagen- Induced Arthritis (CIA). BACKGROUND: Rheumatoid arthritis (RA) is a complex immune disease characterized by bilateral symmetrical multi-joint pain and swelling. Si Shen Decoction (SSD) has shown good results in treating RA in clinical applications, but its mechanism of action remains unclear. OBJECTIVE: To investigate the mechanism of SSD in rats with Collagen-Induced Arthritis (CIA). METHODS: Bioinformatics and network pharmacology analyses were used to predict the possible treatment targets and signaling pathways. Elisa, Western blotting, and quantitative real-time polymerase chain reaction were used to verify the mechanism of SSD in the treatment of RA. RESULTS: FABP4, MMP9, and PTGS2 were the most common predicted therapeutic targets. SSD treatment significantly reduced synovitis, ankle swelling and bone erosion in CIA rats. The SSD group also significantly reduced the serum secretion of CRP, TNFα, and IL1ß, decreased mRNA levels of FABP4, IKKα, and p65 in the synovial membrane, but increased PPARγ. Western blot showed that SSD treatment could significantly reduce the expression of FABP4, IKKα, and phosphorylated p65 (p-p65) proteins in the synovium. SSD was found to inhibit the FABP4/PPARγ/NFκB signaling pathway and reduce the inflammatory response in CIA rats. The therapeutic effect of SSD was significant with the increase of dose. CONCLUSION: SSD can relieve joint symptoms in CIA rats and alleviate inflammation by inhibiting the FABP4/PPARγ/NFκB signaling pathway. The effect of high-dose SSD was more prominent.

High Accuracy of Clinical Verification of Electrohydrodynamic-Driven Nanobox-on-Mirror Platform for Molecular Identification of Respiratory Viruses.

The molecular detection of multiple respiratory viruses provides evidence for the rational use of drugs and effective health management. Herein, we developed and tested the clinical performance of an electrohydrodynamic-driven nanobox-on-mirror platform (E-NoM) for the parallel, accurate, and sensitive detection of four respiratory viral antigens. The E-NoM platform uses gold-silver alloy nanoboxes as the core material with the deposition of a silver layer as a shell on the core surfaces to amplify and enable a reproducible Raman signal readout that facilitates accurate detection. Additionally, the E-NoM platform employs gold microelectrode arrays as the mirror with electrohydrodynamics to manipulate the fluid flow and enhance molecular interactions for an improved biosensing response. The presence of viral antigens binds the nanobox-based core-shell nanostructure on the gold microelectrode and creates the nanocavity with extremely strong "hot spots" to benefit sensitive analysis. Significantly, in a large clinical cohort with 227 patients, the designed E-NoM platform demonstrates the capability of screening respiratory infection with achieved clinical specificity, sensitivity, and accuracy of 100.0, 96.48, and 96.91%, respectively. It is anticipated that the E-NoM platform can find a position in clinical usage for respiratory disease diagnosis.

A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTSNE). These NTSNE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTSNE→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

Impaired neuronal macroautophagy in the prelimbic cortex contributes to comorbid anxiety-like behaviors in rats with chronic neuropathic pain.

A large proportion of patients with chronic pain experience co-morbid anxiety. The medial prefrontal cortex (mPFC) is proposed to underlie this comorbidity, but the molecular and neuronal mechanisms are not fully understood. Here, we reported that impaired neuronal macroautophagy in the prelimbic cortical (PrL) subregion of the mPFC paralleled the occurrence of anxiety-like behaviors in rats with chronic spared nerve injury (SNI). Intriguingly, such macroautophagy impairment was mainly observed in a FOS/c-Fos+ neuronal subpopulation in the PrL. Chemogenetic inactivation of this comorbid anxiety-related neuronal ensemble relieved pain-induced anxiety-like behaviors. Rescuing macroautophagy impairment in this neuronal ensemble relieved chronic pain-associated anxiety and mechanical allodynia and restored synaptic homeostasis at the molecular level. By contrast, artificial disruption of macroautophagy induced early-onset co-morbid anxiety in neuropathic rats, but not general anxiety in normal rats. Taken together, our work identifies causal linkage between PrL neuronal macroautophagy dysfunction and comorbid anxiety in neuropathic pain and provides novel insights into the role of PrL by differentiating its contribution in pain-induced comorbid anxiety from its modulation over general anxiety-like behaviors.Abbreviation: AAV: adeno-associated viruses; ACC: anterior cingulate cortex; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; CAMK2/CaMKII: calcium/calmodulin-dependent protein kinase II; CNO: clozapine-N-oxide; CQ: chloroquine; DIA: data independent acquisition; DIO: double floxed inverse orf; DLG4/PSD-95: discs large MAGUK scaffold protein 4; Dox: doxycycline; GABA: γ-aminobutyric acid; GFP: green fluorescent protein; GO: gene ontology; Gi: inhibitory guanine nucleotide-binding proteins; HsCHRM4/M4D: human cholinergic receptor muscarinic 4; HsSYN: human synapsin; KEGG: Kyoto encyclopedia of genes and genomes; LAMP1: lysosomal-associated membrane protein 1; LC3-II: PE conjugated microtubule-associated protein 1 light chain3; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; mPFC: medial prefrontal cortex; P2A: 2A self-cleaving peptide; PPI: protein-protein interaction networks; PrL: prelimbic cortex; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; rtTA: reverse tetracycline-transactivator; SDS-PAGE: sodium dodecylsulfate-polyacrylamide gel electrophoresis; SHANK3: SH3 and multiple ankyrin repeat domains 3; SLC1A1/EAAC1: solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, systemXag), member 1; SNAP23: synaptosomal-associated protein 23; SNI:spared nerve injury; SQSTM1/p62: sequestosome 1; SYT3: synaptotagmin 3; TRE: tetracycline-responsive element; TRE3G: third-generation tetracycline-responsive element.

Stability of gut microbiome after COVID-19 vaccination in healthy and immuno-compromised individuals.

Bidirectional interactions between the immune system and the gut microbiota are key contributors to various physiological functions. Immune-associated diseases such as cancer and autoimmunity, and efficacy of immunomodulatory therapies, have been linked to microbiome variation. Although COVID-19 infection has been shown to cause microbial dysbiosis, it remains understudied whether the inflammatory response associated with vaccination also impacts the microbiota. Here, we investigate the temporal impact of COVID-19 vaccination on the gut microbiome in healthy and immuno-compromised individuals; the latter included patients with primary immunodeficiency and cancer patients on immunomodulating therapies. We find that the gut microbiome remained remarkably stable post-vaccination irrespective of diverse immune status, vaccine response, and microbial composition spanned by the cohort. The stability is evident at all evaluated levels including diversity, phylum, species, and functional capacity. Our results indicate the resilience of the gut microbiome to host immune changes triggered by COVID-19 vaccination and suggest minimal, if any, impact on microbiome-mediated processes. These findings encourage vaccine acceptance, particularly when contrasted with the significant microbiome shifts observed during COVID-19 infection.

Influence of operator's experience on complications of root canal treatment using contemporary techniques: a retrospective study.

BACKGROUND: Endodontic treatment has benefited from the development of new techniques and equipment. Few clinical studies have been published on the complications associated with root canal preparations performed by doctors with different working experiences using contemporary techniques. This study aimed to analyze the complications of endodontic treatment performed by residents and endodontic specialists in a teaching stomatology hospital using contemporary techniques. METHODS: Cases of root canal treatment (RCT) and non-surgical root canal retreatment (ReRCT) performed by residents with 1-3 years of experience and endodontic specialists with 5-7 years of experience were collected from the electronic medical system of the Department of Endodontics, Beijing Stomatology Hospital, from September 1, 2020 to August 31, 2021. The cases were examined in terms of patient age, sex, type of tooth, diagnosis, treatment modality (RCT or ReRCT), number of appointments, whether an operating microscope was used, presence of ledges, canal transportation, perforations, missed canals, separated instruments, flare-ups and clinical incidence of second mesiobuccal (MB2) root canal in the maxillary molars. RESULTS: In total, 859 teeth from 820 patients were included in the analysis. The overall incidence of complications in the resident group was significantly higher than that in the specialist group. More ledges and flare-ups were observed in the resident group (p < 0.05). The clinical incidence of MB2 was significantly higher in the specialist group (p < 0.05). There were no significant differences in root canal transportation, perforation, or instrument separation between the two groups (p < 0.05). Multivariate analysis showed that the incidence of root canal preparation complications was related to operator experience, tooth type and treatment modality. CONCLUSIONS: Technical advancements could reduce the effect of working experience on RCT complications between residents and endodontic specialists in a teaching stomatology hospital.

The weakened physiological functions of human serum albumin in presence of polystyrene nanoplastics.

Due to the widespread presence of nanoplastics (NPs) in daily essentials and drinking water, the potential adverse effects of NPs on human health have become a global concern. Human serum albumin (HSA), the most abundant and multi-functional protein in plasma, has been chosen to understand the biological effects of NPs after entering the blood. The esterase activity and the transport of bisphenol A in the presence of polystyrene nanoplastics (PSNPs) under physiological conditions (pH 4.0 and 7.4) have been investigated to evaluate the possible biological effects. The interactions between PSNPs and HSA have also been systematically studied by multispectral methods and dynamic light scattering techniques. The esterase activity of HSA presented a decreased trend with increasing PSNPs; conversely, higher permeabilities are accompanied by higher amounts of PSNPs. Compared with the unchanged hydrodynamic diameter and weaker interactions at pH 7.4, stronger binding between HSA and PSNPs at pH 4.0 led to a significant increase in the particle size of the PSNPs-HSA complex. The quenching mechanism belonged to the static quenching type. The electrostatic force is proposed to be the dominant factor for PSNPs binding to HSA. The work provides some information about the toxicity of NPs when exposed to humans.

ER body-resident myrosinases and tryptophan specialized metabolism modulate root microbiota assembly.

Endoplasmic reticulum (ER) bodies are ER-derived structures that contain a large amount of PYK10 myrosinase, which hydrolyzes tryptophan (Trp)-derived indole glucosinolates (IGs). Given the well-described role of IGs in root-microbe interactions, we hypothesized that ER bodies in roots are important for interaction with soil-borne microbes at the root-soil interface. We used mutants impaired in ER bodies (nai1), ER body-resident myrosinases (pyk10bglu21), IG biosynthesis (myb34/51/122), and Trp specialized metabolism (cyp79b2b3) to profile their root microbiota community in natural soil, evaluate the impact of axenically collected root exudates on soil or synthetic microbial communities, and test their response to fungal endophytes in a mono-association setup. Tested mutants exhibited altered bacterial and fungal communities in rhizoplane and endosphere, respectively. Natural soils and bacterial synthetic communities treated with mutant root exudates exhibited distinctive microbial profiles from those treated with wild-type (WT) exudates. Most tested endophytes severely restricted the growth of cyp79b2b3, a part of which also impaired the growth of pyk10bglu21. Our results suggest that root ER bodies and their resident myrosinases modulate the profile of root-secreted metabolites and thereby influence root-microbiota interactions.

Interpretable Machine Learning Model to Predict Bone Cement Leakage in Percutaneous Vertebral Augmentation for Osteoporotic Vertebral Compression Fracture Based on SHapley Additive exPlanations.

STUDY DESIGN: Retrospective study. OBJECTIVES: Our objective is to create comprehensible machine learning (ML) models that can forecast bone cement leakage in percutaneous vertebral augmentation (PVA) for individuals with osteoporotic vertebral compression fracture (OVCF) while also identifying the associated risk factors. METHODS: We incorporated data from patients (n = 425) which underwent PVA. To predict cement leakage, we devised six models based on a variety of parameters. Evaluate and juxtapose the predictive performances relied on measures of discrimination, calibration, and clinical utility. SHapley Additive exPlanations (SHAP) methodology was used to interpret model and evaluate the risk factors associated with cement leakage. RESULTS: The occurrence rate of cement leakage was established at 50.4%. A binary logistic regression analysis identified cortical disruption (OR 6.880, 95% CI 4.209-11.246), the basivertebral foramen sign (OR 2.142, 95% CI 1.303-3.521), the fracture type (OR 1.683, 95% CI 1.083-2.617), and the volume of bone cement (OR 1.198, 95% CI 1.070-1.341) as independent predictors of cement leakage. The XGBoost model outperformed all others in predicting cement leakage in the testing set, with AUC of .8819, accuracy of .8025, recall score of .7872, F1 score of .8315, and a precision score of .881. Several important factors related to cement leakage were drawn based on the analysis of SHAP values and their clinical significance. CONCLUSION: The ML based predictive model demonstrated significant accuracy in forecasting bone cement leakage for patients with OVCF undergoing PVA. When combined with SHAP, ML facilitated a personalized prediction and offered a visual interpretation of feature importance.

Comprehensive molecular expression profiling of SARS-CoV-associated factors in the endometrium across the menstrual cycle and elevated susceptibility in women with recurrent pregnancy loss.

Objective: To evaluate the dynamic expression profiling alterations of SARS-CoV-2-associated molecules within the fertile human endometrium throughout the menstrual cycle. Furthermore, to explore the inherent vulnerability of the endometrium to SARS-CoV-2 infection among women experiencing recurrent pregnancy failure, including both recurrent implantation failures (RIF) and recurrent pregnancy losses (RPL). Method: The present study employed multiple datasets to investigate the expression patterns of SARS-CoV-2-associated genes. Firstly, a single-cell RNA-sequencing dataset comprising endometrial samples from 19 healthy women across the menstrual cycle was utilized. Additionally, two microarray datasets encompassing 24 women with RIF, and 24 women with RPL during the peri-implantation phase were included. To complement these analyses, immunohistochemical (IHC) staining was performed on endometrial samples collected from 30 women with RIF, 30 women with RPL, and 20 fertile controls recruited specifically during the implantation period. Results: The investigation revealed a moderate expression percentage of CTSL (22%), TMPRSS4 (15%), FURIN (16%) and MX1 (9%) in endometrium. Conversely, the expression percentages of ACE2 (1%) and TMPRSS2 (4%) were relatively low. Notably, the expression of BSG exhibited an increment towards the window of implantation, reaching its peak during the middle secretary phase. Furthermore, a significant reduction (p < 0.05) in TMPRSS2 expression was observed in the RIF group compared to the control group. While the expression of BSG was significantly increased (p < 0.05) in the RPL group, findings that were corroborated by the IHC staining results. Conclusion: The findings of this study indicate a noteworthy upregulation of BSG expression in the endometrium of women with RPL. These results suggest an augmented susceptibility of endometrium to SARS-CoV-2 infection, potentially contributing to unfavorable pregnancy outcomes.

Progress on lysosomal PPT1-mediated regulation of cellular homeostasis and pathogenesis.

Palmitoyl protein thioesterase 1(PPT1) is a lysosomal enzyme that catalyzes the protein depalmitoylation. It is considered to play a crucial role in regulating lysosomes, mitochondria and lipid metabolism. PPT1 has been reported to play an important role in the occurrence and progression of diseases, such as neurological diseases and cancers. However, the regulatory mechanisms remain unknown. In this review, we summarize the progress of PPT1 function and mechanisms in neurological disorders and cancers, which will provide as reference and guidance for exploring the regulatory mechanisms of PPT1 and developing new drugs for treating related diseases in the future.

Clonal cooperation through soluble metabolite exchange facilitates metastatic outgrowth by modulating Allee effect.

Cancers feature substantial intratumoral heterogeneity of genetic and phenotypically distinct lineages. Although interactions between coexisting lineages are emerging as a potential contributor to tumor evolution, the extent and nature of these interactions remain largely unknown. We postulated that tumors develop ecological interactions that sustain diversity and facilitate metastasis. Using a combination of fluorescent barcoding, mathematical modeling, metabolic analysis, and in vivo models, we show that the Allee effect, i.e., growth dependency on population size, is a feature of tumor lineages and that cooperative ecological interactions between lineages alleviate the Allee barriers to growth in a model of triple-negative breast cancer. Soluble metabolite exchange formed the basis for these cooperative interactions and catalyzed the establishment of a polyclonal community that displayed enhanced metastatic dissemination and outgrowth in xenograft models. Our results highlight interclonal metabolite exchange as a key modulator of tumor ecology and a contributing factor to overcoming Allee effect-associated growth barriers to metastasis.

The mechanism of DEHP degradation by the combined action of biochar and Arthrobacter sp. JQ-1: Mechanisms insight from bacteria viability, degradation efficiency and changes in extracellular environment.

Di(2-ethylhexyl) phthalate (DEHP) has been widely detected in soil, water, and sediment as a priority control pollutant. Immobilized microorganism technology is gradually mature and applied in production. Biochar prepared from agricultural wastes is an excellent immobilized carrier because of its porous structure and abundant functional groups. Environmental acidification was caused by degrading bacteria Arthrobacter sp. JQ-1 (JQ-1) respiration and acidic metabolites during DEHP degradation, which affected the passage life of microorganisms and the removal efficiency of DEHP. The mechanism of DEHP degradation by the combined action of JQ-1 and corn straw biochar (BC) at 600 °C was investigated, and bacterial viability, microenvironmental changes, and kinetic tests were performed in this research. Compared with biodegradation group alone, the degradation rate of DEHP in 1% biochar unloaded and loaded with JQ-1 increased by 18.3% and 30.9%, and its half-life decreased to 23.90 h and 11.95h, a reduction of 31.37 h. The percentage of detected living JQ-1 increased as biochar content increased when loading capacity was less than 1%. In which, (JQ-1-BC2) group was 4.1% higher than (JQ-1-BC1) group. Biochar has the ability to neutralize acidifying environmental pH due to its alkaline functional groups, including lactone group, -OH, -COO-. 1% biochar loaded with JQ-1 increased the pH of the microenvironment by 0.57 and alkaline phosphatase (AKP) activity by 0.0063 U·mL-1, which promoted the reduction of PA. Study suggested that biochar loaded with JQ-1 could simultaneously adsorb and degrade DEHP during the process of DEHP removal. Biochar could be used as a biological stimulant to increase abundance and metabolism, enhance the utilization of DEHP by JQ-1. Biochar (1% (w/v)) loaded with JQ-1 as DEHP removal material showed good performance. Biochar not only as an immobilized carrier, but also as a biostimulant, providing an effective strategy for the collaborative remediation of PAEs contaminated.

Analysis of myosin genes in HNSCC and identify MYL1 as a specific poor prognostic biomarker, promotes tumor metastasis and correlates with tumor immune infiltration in HNSCC.

Head neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors which ranks the sixth incidence in the world. Although treatments for HNSCC have improved significantly in recent years, its recurrence rate and mortality rate remain high. Myosin genes have been studied in a variety of tumors, however its role in HNSCC has not been elucidated. GSE58911 and GSE30784 gene expression profile analysis were performed to detect significantly dys-regulated myosin genes in HNSCC. The Cancer Genome Atlas (TCGA) HNSCC database was used to verify the dys-regulated myosin genes and study the relationship between these genes and prognosis in HNSCC. The results showed that MYL1, MYL2, MYL3, MYH2, and MYH7 were down-regulated, while MYH10 was up-regulated in patients with HNSCC. Interestingly, MYL1, MYL2, MYH1, MYH2, and MYH7 were shown to be unfavorable prognostic markers in HNSCC. It is also worth noting that MYL1 was a specific unfavorable prognostic biomarker in HNSCC. MYL1, MYL2, MYL3, MYH2, MYH7, and MYH10 promoted CD4 + T cells activation in HNSCC. MYL1 was proved to be down-regulated in HNSCC tissues compared to normal tissues at protein levels. MYL1 overexpression had no effect on proliferation, but significantly promoted migration of Fadu cells. MYL1 increased EGF and EGFR protein expression levels. Moreover, there is a positive correlation between MYL1 expression and Tcm CD8 cells, Tcm CD4 + cells, NK cells, Mast cells, NKT cells, Tfh cells and Treg cells in HNSCC. Overall, MYL1 facilitates tumor metastasis and correlates with tumor immune infiltration in HNSCC and these effects may be associated with the EGF/EGFR pathway.

Research progress of implantation materials and its biological evaluation.

With the development of modern material science, life science and medical science, implantation materials are widely employed in clinical fields. In recent years, these materials have also evolved from inert supports or functional substitutes to bioactive materials able to trigger or promote the regenerative potential of tissues. Reasonable biological evaluation of implantation materials is the premise to make sure their safe application in clinical practice. With the continual development of implantation materials and the emergence of new implantation materials, new challenges to biological evaluation have been presented. In this paper, the research progress of implantation materials, the progress of biological evaluation methods, and also the characteristics of biocompatibility evaluation for novel implantation materials, like animal-derived implantation materials, nerve contact implantation materials, nanomaterials and tissue-engineered medical products were reviewed in order to provide references for the rational biological evaluation of implantable materials.

Binding divergence of polystyrene nanoparticles with serum albumin caused by surface functionalization.

Using a combination of spectroscopy, we devised an integrated structural strategy to comprehensively profile the molecular details of the impact of differently functionalized (plain, aminated, and carboxylated) polystyrene nanoparticles (PSNPs) on human serum albumin (HSA). The binding isotherms obtained from fluorescence and UV-vis absorption measurements demonstrate that surface functionalization can distinguish the interaction of PSNPs with HSA. Three-dimensional fluorescence and circular dichroism analysis of the effect of interaction with PSNPs on the native conformation and secondary structures of the protein reveals a diminution in the skeleton structure of HSA induced by the PSNPs. In accordance with this, it is discovered that the esterase activity of protein-PSNPs aggregates is diminished compared to that of the native protein. The carboxylated PSNPs exhibited the strongest protein binding and perturbation effects compared to other particles. Plain PSNPs exhibited significant hydrophobic interaction properties, as evidenced by spectral blue shifts and a diminished Stokes shift in the three-dimensional fluorescence assay. Our results exclusively highlight that the hydrophobic and surface charge characteristics of PSNPs govern the extent of interaction with the protein, which is beneficial to understanding microplastic toxicology.

Single-cell RNA sequencing reveals tumor immune microenvironment in human hypopharygeal squamous cell carcinoma and lymphatic metastasis.

Background: Human hypopharygeal squamous cell carcinoma (HSCC) is a common head and neck cancer with a poor prognosis in advanced stages. The occurrence and development of tumor is the result of mutual influence and co-evolution between tumor cells and tumor microenvironment (TME). Tumor immune microenvironment (TIME) refers to the immune microenvironment surrounding tumor cells. Studying TIME in HSCC could provide new targets and therapeutic strategies for HSCC. Methods: We performed single-cell RNA sequencing (scRNA-seq) and analysis of hypopharyngeal carcinoma, paracancerous, and lymphoid tissues from five HSCC patients. Subdivide of B cells, T cells, macrophages cells, and monocytes and their distribution in three kinds of tissues as well as marker genes were analyzed. Different genes of IGHG1 plasma cells and SPP1+ macrophages between HSCC tissues, adjacent normal tissues and lymphatic tissues were analyzed. Additionally, we studied proliferating lymphocytes, T cells exhaustion, and T cell receptor (TCR) repertoire in three kinds of tissues. Results: Transcriptome profiles of 132,869 single cells were obtained and grouped into seven cell clusters, including epithelial cells, lymphocytes, mononuclear phagocytics system (MPs), fibroblasts, endothelial cells (ECs), plasmacytoid dendritic cells (pDCs), and mast cells. Tumor metastasis occurred in three lymphoid tissues. Four distinct populations were identified from lymphocytes, including B cells, plasma cells, T cells and proliferating lymphocytes. We found IGHA1 and IGHG1 specific plasma cells significantly overexpressed in HSCC tissues compared with normal hypopharygeal tissues and lymphatic tissues. Five distinct populations from MPs were identified, including macrophages, monocytes, mature dendritic cells (DCs), Type 1 conventional dendritic cells (cDC1) and Type 2 conventional dendritic cells (cDC2). SPP1+ macrophages were significantly overexpressed in HSCC tissues and lymphatic tissues compared with normal hypopharygeal tissues, which are thought to be M2-type macrophages. Exhaustion of CD8+ Teff cells occurred in HSCC tissues. At last, we verified that IgA and IgG1 protein expression levels were significantly up-regulated in HSCC tissues compared to adjacent normal tissues. Conclusion: Overall, this study revealed TIME in HSCC and lymphatic metastasis, and provided potential therapeutic targets for HSCC.