All-In-One OsciDrop Digital PCR System for Automated and Highly Multiplexed Molecular Diagnostics.

Digital PCR (dPCR) holds immense potential for precisely detecting nucleic acid markers essential for personalized medicine. However, its broader application is hindered by high consumable costs, complex procedures, and restricted multiplexing capabilities. To address these challenges, an all-in-one dPCR system is introduced that eliminates the need for microfabricated chips, offering fully automated operations and enhanced multiplexing capabilities. Using this innovative oscillation-induced droplet generation technique, OsciDrop, this system supports a comprehensive dPCR workflow, including precise liquid handling, pipette-based droplet printing, in situ thermocycling, multicolor fluorescence imaging, and machine learning-driven analysis. The system's reliability is demonstrated by quantifying reference materials and evaluating HER2 copy number variation in breast cancer. Its multiplexing capability is showcased with a quadruplex dPCR assay that detects key EGFR mutations, including 19Del, L858R, and T790M in lung cancer. Moreover, the digital stepwise melting analysis (dSMA) technique is introduced, enabling high-multiplex profiling of seven major EGFR variants spanning 35 subtypes. This innovative dPCR system presents a cost-effective and versatile alternative, overcoming existing limitations and paving the way for transformative advances in precision diagnostics.

Multimodal image fusion-assisted endoscopic evacuation of spontaneous intracerebral hemorrhage.

PURPOSE: Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods. METHODS: This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Non-normally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher's exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. RESULTS: A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time (p < 0.001), less blood loss (p < 0.001), better hematoma evacuation (p = 0.003), and a shorter stay in the intensive care unit (p = 0.002) than patients who underwent TC. Based on clinical characteristics and analysis of perioperative complications, there is no significant difference between the 2 surgical methods. Modified Rankin scale scores at 180 days were better in the MINS than in the TC group (p = 0.014). CONCLUSIONS: Compared with TC for the treatment of ICH, MINS is safer and more efficient in cleaning ICH, which improved the prognosis of the patients. In the future, a larger sample size clinical trial will be needed to evaluate its efficacy.

Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model.

Long-term mechanical ventilation after tracheotomy is a common treatment in intensive care unit patients. This study investigated the differences among the effects of different wetting states on the airway, lung, and serum inflammatory factors. New Zealand rabbits (n = 36) were selected to construct tracheotomy models and then divided into four groups: Model, Mask, YTH, and Sham groups. Lung tissue dry/wet ratio was used to evaluate the humidification effect; cytokines, including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-10, were used to evaluate the inflammatory response; hematoxylin and eosin staining was used to evaluate the histopathology. Post hoc analysis based on the Dunnett t-test was applied. A self-developed integrated wetting device could increase the utilization of wetting solution, enhance the effect of wetting to protect tissue integrity, and suppress airway inflammation, reducing the expression of pro-inflammatory factors while promoting the expression of anti-inflammatory factor IL-10 to inhibit the inflammatory response, compared to other methods. The integrated humidification device provided a new method for clinical nursing practice, improving clinical efficiency and reducing nursing workload. Further clinical trials are required to test its effectiveness and safety in the clinic.

Comparison of microwave and hot-air roasting on microstructure of sesame seed, aroma-active, hazardous components, and sensory perception of sesame oil.

The unclear effects of microwaves, as a greener alternative to hot air, on sensory perception, aroma, and hazardous components of sesame oil were investigated. Microwaves (900 W, 6-10 min) created more seed porosity and cell destruction and facilitated more γ-tocopherol release in sesame oil (349.30-408.50 mg/kg) than 200 °C, 20 min hot air (304.90 mg/kg). Microwaves (6-10 min) generated more aromatic heterocyclics (42.40-125.12 mg/kg) and aldehydes (5.15-2.08 mg/kg) in sesame oil than hot air (25.59 mg/kg and 1.34 mg/kg). Microwaves (6 min) produced sesame oil with a stronger roasted sesame flavour, and weaker bitter and burnt flavour than hot air. Microwaves reduced harman (≤775.19 ng/g), norharman (≤1,069.99 ng/g), and benzo(a)pyrene (≤1.59 µg/kg) in sesame oil than hot air (1,319.85 ng/g, 1,168.40 ng/g, and 1.83 µg/kg). Appropriate microwave is a promising alternative to hot air in producing sesame oil with a better sensory profile, more bioactive, and less carcinogenic components.

The use of histotripsy as intratumoral immunotherapy beyond tissue ablation-the rationale for exploring the immune effects of histotripsy.

Mechanical high-intensity focused ultrasound (M-HIFU), which includes histotripsy, is a non-ionizing, non-thermal ablation technology that can be delivered by noninvasive methods. Because acoustic cavitation is the primary mechanism of tissue disruption, histotripsy is distinct from the conventional HIFU techniques resulting in hyperthermia and thermal injury. Phase I human trials have shown the initial safety and efficacy of histotripsy in treating patients with malignant liver tumors. In addition to tissue ablation, a promising benefit of M-HIFU has been stimulating a local and systemic antitumor immune response in preclinical models and potentially in the Phase I trial. Preclinical studies combining systemic immune therapies appear promising, but clinical studies of combinations have been complicated by systemic toxicities. Consequently, combining M-HIFU with systemic immunotherapy has been demonstrated in preclinical models and may be testing in future clinical studies. An additional alternative is to combine intratumoral M-HIFU and immunotherapy using microcatheter-placed devices to deliver both M-HIFU and immunotherapy intratumorally. The promise of M-HIFU as a component of anti-cancer therapy is promising, but as forms of HIFU are tested in preclinical and clinical studies, investigators should report not only the parameters of the energy delivered but also details of the preclinical models to enable analysis of the immune responses. Ultimately, as clinical trials continue, clinical responses and immune analysis of patients undergoing M-HIFU including forms of histotripsy will provide opportunities to optimize clinical responses and to optimize application and scheduling of M-HIFU in the context of the multi-modality care of the cancer patient.

Anaerobic digestion of hydrothermally pretreated dewatered sewage sludge: effects of process conditions on methane production and the fate of phosphorus.

The hydrothermal pretreatment (HTP) characteristics and the fate of phosphorus (P) and anaerobic digestion (AD) performance of dewatered sewage sludge (DSS) were investigated at different hydrothermal conditions. The maximum methane yield reached 241 mL CH4/g COD when the hydrothermal conditions were 200 °C-2 h-10% (A4), and the yield was 78.28% higher than that without pretreatment (A0) and 29.62% higher than that of the initial hydrothermal conditions (A1, 140 °C-1 h-5%). Proteins, polysaccharides, and volatile fatty acids (VFAs) were the main hydrothermal products of DSS. 3D-EEM analysis revealed that tyrosine, tryptophan proteins, and fulvic acids decreased after HTP, but the content of humic acid-like substances increased, and this phenomenon was more noticeable after AD. Solid-organic P was converted into liquid-P during the hydrothermal process, and nonapatite inorganic P was converted into organic P during AD. All samples achieved positive energy balance, and the energy balance of A4 was 10.50 kJ/g VS. Microbial analysis showed that the composition of the anaerobic microbial degradation community changed as the sludge organic composition was altered. Results showed that the HTP improved the anaerobic digestion of DSS.

Baicalin Reduces Immune Cell Infiltration by Inhibiting Inflammation and Protecting Tight Junctions in Ischemic Stroke Injury.

Ischemic stroke is a serious health hazard that lacks effective treatment strategies. This study aims to investigate baicalin's effect on tight junctions and immune cell infiltration after ischemic stroke injury. Rat brain microvascular endothelial cells (BMECs) were treated with OGD/R to establish an in vitro model. Caspase-3, Bax, Bcl-2, zonula occludens-1 (ZO-1), occludin, claudin-5, tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-6, inducible nitric oxide synthase (iNOS), Toll-like receptor (TLR) 2, TLR4, and nuclear factor-kappa B (NF-[Formula: see text]B) expressions were detected using qRT-PCR and western blotting. ZO-1, TNF-[Formula: see text], iNOS, IL6, CD31, and ZO-1 expressions were examined using immunofluorescence. A tube formation assay was performed to measure angiogenesis. An ischemia-reperfusion model in rats was established by middle cerebral artery occlusion. The infarct volume was observed using 2,3,5-triphenyltetrazolium chloride staining. TNF-[Formula: see text], iNOS, and IL6 levels in the serum were tested using ELISA. Flow cytometry was performed to examine immune cell inflammatory infiltration. Baicalin had no significant effect on the proliferation of normal BMECs. Baicalin inhibited apoptosis, protected against tight junction injury, and alleviated the inflammatory response in OGD/R-induced BMECs and IR rats, with the highest dose (25[Formula: see text][Formula: see text]g/mL) exerting a superior effect. Baicalin decreased the neurological function score, infarct volume, and brain water content, relieved brain morphological changes, and inhibited immune cell infiltration in vivo. In conclusion, baicalin could reduce BMECs apoptosis, protect tight junctions, and resist immune cell infiltration, thereby alleviating ischemic stroke. Our findings potentially provide a novel treatment strategy for ischemic stroke.

Coupling Plant Polyphenol Coordination Assembly with Co(OH)2 to Enhance Electrocatalytic Performance towards Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) is kinetically sluggish due to the limitation of the four-electron transfer pathway, so it is imperative to explore advanced catalysts with a superior structure and catalytic output under facile synthetic conditions. In the present work, an easily accessible strategy was proposed to implement the plant-polyphenol-involved coordination assembly on Co(OH)2 nanosheets. A TA-Fe (TA = tannic acid) coordination assembly growing on Co(OH)2 resulted in the heterostructure of Co(OH)2@TA-Fe as an electrocatalyst for OER. It could significantly decrease the overpotential to 297 mV at a current density of 10 mA cm-2. The heterostructure Co(OH)2@TA-Fe also possessed favorable reaction kinetics with a low Tafel slope of 64.8 mV dec-1 and facilitated a charge-transfer ability. The enhanced electrocatalytic performance was further unraveled to be related to the confined growth of the coordination assembly on Co(OH)2 to expose more active sites, the modulated surface properties and their synergistic effect. This study demonstrated a simple and feasible strategy to utilize inexpensive biomass-derived substances as novel modifiers to enhance the performance of energy-conversion electrocatalysis.

LncRNA H19 via miR-29a-3p is involved in lung inflammation and pulmonary fibrosis induced by neodymium oxide.

The occupational and environmental health safety of rare earths has attracted considerable attention. In China, the rare earth neodymium oxide (Nd2O3) is extensively refined and utilized. However, the mechanisms of Nd2O3-induced lung injury are elusive. In the present study, we found that exposure of mice to Nd2O3 caused an inflammatory reaction and fibrosis in lung tissues, which was in relation to the Nd2O3-induced higher levels of the lncRNA H19 (H19), tumor necrosis factor receptor 1 (TNFRSF1A), p-p65, and p-IKKß and lower levels of miR-29a-3p. Further, in mouse monocyte macrophage leukemia cells (RAW264.7), Nd2O3 induced an inflammatory reaction, increases of H19 and TNFRSF1A levels, decreases of miR-29a-3p levels, and activation of the nuclear factor (NF)-κB signaling pathway. Further, we established that miR-29a-3p regulates TNFRSF1A expression. Up-regulation of miR-29a-3p and down-regulation of H19 blocked the Nd2O3-induced secretion of TNF-α, MIP-1α, and IL-6; the increases of TNFRSF1A levels; and activation of the NF-κB signaling pathway in RAW264.7 cells. Further, in Nd2O3-treated RAW26.4 cells, H19 inhibited the expression of miR-29a-3p, which targets TNFRSF1A, and activated the NF-κB signaling pathway to enhance the expression of TNF-α, MIP-1α, and IL-6. Moreover, for mice, up-regulation of miR-29a-3p reversed lung tissue inflammation, pulmonary fibrosis, and activation of the NF-κB signaling pathway induced by Nd2O3. In sum, the present investigation shows that H19 via miR-29a-3p is involved in lung inflammation and pulmonary fibrosis induced by Nd2O3, which is a mechanism for the Nd2O3-induced lung inflammatory response and pulmonary fibrosis. This information is useful for development of a biomarker of Nd2O3-induced lung injury.

Transcriptome Profiling of A549 Xenografts of Nonsmall-cell Lung Cancer Treated with Qing-Re-Huo-Xue Formula.

Lung cancer is one of the most common malignant tumors, and non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. Chinese herbal formula Qing-Re-Huo-Xue (QRHXF) has shown antitumor effects in the NSCLC xenograft mouse model of Lewis cells. However, the molecular mechanisms underlying the antitumor effects of QRHXF remain unknown. In this study, an A549 xenograft mouse model was established, and the mice were then treated with QRHXF or vehicle through oral gavage. Tumor growth was monitored. Tumors were subsequently harvested, and RNA sequencing was performed. Compared with the control group, mice treated with QRHXF showed smaller tumor size and slower tumor growth. RNA sequencing results indicated 36 differentially expressed genes between QRHXF treated and control groups. 16 upregulated and 20 downregulated genes were identified. Enrichment analysis showed four differential expression genes (DEGs) related to tumor growth pathways RASAL2, SerpinB5, UTG1A4, and PDE3A. In conclusion, this study revealed that QRHXF could inhibit tumor growth in an A549 xenograft mouse model, and the target genes of QRHXF may include PDE3A, RASAL2, SERPIB5, and UTG1A4.

Associations of C-X-C motif chemokine ligands 1/2/8/13/14 with clinicopathological features and survival profile in patients with colorectal cancer.

The present study aimed to assess the correlation of C-X-C motif chemokine ligand (CXCL)1, CXCL2, CXCL8, CXCL13 and CXCL14 with clinicopathological features and survival profile in patients with colorectal cancer (CRC). Patients with primary CRC (n=232) were retrospectively reviewed, with their tumor tissue specimens acquired from the Department of Pathology (The First Hospital of Jilin University, Changchun, China), their demographic data and preoperative tumor features collected from the hospital database, and their survival data obtained from the follow-up documents. Tumor CXCL expression was detected by immunohistochemistry (IHC). Based on the total IHC score, the expression of CXCL1, CXCL2, CXCL8, CXCL13 and CXCL14 was categorized as low expression (IHC score ≤3) and high expression (IHC score >3). CXCL1 (51.3% high and 48.7% low), CXCL2 (59.9% high and 40.1% low), CXCL8 (44.4% high and 55.6% low), CXCL13 (40.9% high and 59.1% low) and CXCL14 (31.0% high and 69.0% low) were expressed in CRC tumor tissues, and their expression levels were correlated with each other, except between CXCL8 and CXCL14, and between CXCL13 and CXCL14. CXCL1 was associated with a larger tumor size, and an advanced T stage, N stage and Tumor-Node-Metastasis (TNM) stage. CXCL2 was associated with an advanced N stage and TNM stage, and CXCL8 was associated with a greater T stage and TNM stage. CXCL13 was associated with a greater T stage, N stage and TNM stage, while CXCL14 was not associated with any clinical characteristics. As for survival, CXCL1, CXCL2, CXCL8 and CXCL13, but not CXCL14, were associated with poor overall survival (OS) rate, and further multivariate Cox's regression model analysis revealed that CXCL1 independently predicted unfavorable OS in patients with CRC. Overall, CXCL1, CXCL2, CXCL8 and CXCL13 have good potential as an indicator for tumor features and survival in patients with CRC.

LINC01061 triggers inflammation and inflammasome activation in autoimmune thyroiditis via microRNA-612/BRD4 axis.

Considering the significance of LINC01061 in papillary thyroid cancer, here, we commenced to study the role of LINC01061 in autoimmune thyroid disease (AITD) and the potential mechanism. Thyroid tissues were attained from patients with AITD, and Nthy-ori 3-1 cells were induced with lipopolysaccharide (LPS), followed by measurement of LINC01061, microRNA (miR)-612, and BRD4 expression as well as their binding relation. The ectopic expression and silencing experimentations were carried out in LPS-induced Nthy-ori 3-1 cells to detect cell viability and apoptosis as well as inflammation and inflammasome. BRD4 and LINC01061 upregulation and miR-612 downregulation were observed in thyroid tissues of AITD patients and LPS-induced Nthy-ori 3-1 cells. Mechanistic analysis manifested that LINC01061 bound to miR-612 that negatively targeted BRD4. LINC01061 upregulated BRD4 to enhance cell viability, trigger inflammation and inflammasome activation but reduce apoptosis of LPS-induced Nthy-ori 3-1 cells by sponging miR-612. In conclusion, LINC01061 induced the occurrence of AITD by upregulation of miR-612-mediated BRD4 expression.

Parametric Design of Hip Implant With Gradient Porous Structure.

Patients who has been implanted with hip implant usually undergo revision surgery. The reason is that high stiff implants would cause non-physiological distribution loadings, which is also known as stress shielding, and finally lead to bone loss and aseptic loosening. Titanium implants are widely used in human bone tissues; however, the subsequent elastic modulus mismatch problem has become increasingly serious, and can lead to stress-shielding effects. This study aimed to develop a parametric design methodology of porous titanium alloy hip implant with gradient elastic modulus, and mitigate the stress-shielding effect. Four independent adjustable dimensions of the porous structure were parametrically designed, and the Kriging algorithm was used to establish the mapping relationship between the four adjustable dimensions and the porosity, surface-to-volume ratio, and elastic modulus. Moreover, the equivalent stress on the surface of the femur was optimized by response surface methodology, and the optimal gradient elastic modulus of the implant was obtained. Finally, through the Kriging approximation model and optimization results of the finite element method, the dimensions of each segment of the porous structure that could effectively mitigate the stress-shielding effect were determined. Experimental results demonstrated that the parameterized design method of the porous implant with gradient elastic modulus proposed in this study increased the strain value on the femoral surface by 17.1% on average. Consequently, the stress-shielding effect of the femoral tissue induced by the titanium alloy implant was effectively mitigated.

Engineering the hydroxyl content on aluminum oxyhydroxide nanorod for elucidating the antigen adsorption behavior.

The interaction between the aluminum salt-based adjuvants and the antigen in the vaccine formulation is one of the determining factors affecting the immuno-potentiation effect of vaccines. However, it is not clear how the intrinsic properties of the adjuvants could affect this interaction, which limits to benefit the improvement of existing adjuvants and further formulation of new vaccines. Here, we engineered aluminum oxyhydroxide (AlOOH) nanorods and used a variety of antigens including hepatitis B surface antigen (HBsAg), SARS-CoV-2 spike protein receptor-binding domain (RBD), bovine serum albumin (BSA) and ovalbumin (OVA) to identify the key physicochemical properties of adjuvant that determine the antigen adsorption at the nano-bio interface between selected antigen and AlOOH nanorod adjuvant. By using various physicochemical and biophysical characterization methods, it was demonstrated that the surface hydroxyl contents of AlOOH nanorods affected the adsorptive strength of the antigen and their specific surface area determined the adsorptive capacity of the antigen. In addition, surface hydroxyl contents had an impact on the stability of the adsorbed antigen. By engineering the key intrinsic characteristics of aluminum-based adjuvants, the antigen adsorption behavior with the aluminum adjuvant could be regulated. This will facilitate the design of vaccine formulations to optimize the adsorption and stability of the antigen in vaccine.

Boosting the oxygen evolution electrocatalysis of high-entropy hydroxides by high-valence nickel species regulation.

The addition of an extra metal source induces the transformation from crystalline α-Ni(OH)2 to an amorphous NiCoFeCrMo-based high-entropy hydroxide (HEH) and maximizes the high-valence Ni3+ content in HEH. For OER electrocatalysis, the quinary HEH possesses an overpotential of 292 mV at 10 mA cm-2, a Tafel slope of 54.31 mV dec-1 and the boosted intrinsic activity, surpassing other subsystems.

Risk factors for oxaliplatin-induced hypersensitivity reaction in patients with colorectal cancer.

OBJECTIVE: Hypersensitivity reactions with oxaliplatin (OXA) have attracted much attention. This study aimed to analyze the risk factors for OXA-induced hypersensitivity reaction in Chinese colorectal cancer patients through a single-center retrospective investigation. METHODS: The information from 459 colorectal cancer patients treated with OXA in a hospital was collected retrospectively to explore the risk factors for OXA-induced hypersensitivity reaction. RESULTS: Among the 459 patients, 47 (10.24% incidence) cases developed hypersensitivity reactions, with a 3.70% incidence of grade III/IV reaction. The main symptoms included itching, flushing, dyspnea, and rash, which mainly involved skin and adnexa, respiratory system, and nervous system. Dexamethasone pretreatment presented no significant effects on the hypersensitivity reaction (P = 0.282). Multivariate analysis indicated that the previous allergic history (odds ratio (OR) 2.553, 95% confidence interval (CI) 1.139-5.721, P = 0.023) and OXA-free interval (OR 3.605, 95% CI 1.909-6.809, P = 0.000) were independent risk factors for OXA-induced hypersensitivity reaction. CONCLUSIONS: The incidence of OXA-induced hypersensitivity reaction in colorectal cancer patients was similar to those reported in other countries. Clinical medical staff should pay close attention to high-risk factors, such as allergic history and patients having OXA-free intervals in order to avoid or alleviate hypersensitivity reactions.

[Retracted] Downregulation of microRNA­629­5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low­density lipoprotein receptor­related protein 6.

Following the publication of the above paper, it was drawn to the Editors' attention by a concerned reader that certain of the flow cytometric data featured in Fig. 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 44: 1139­1150, 2019; DOI: 10.3892/ijmm.2019.4245].

Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma.

AIMS: Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcomas in patients with other tumor phenotypes, but possible causal relationships between radiotherapy and induction of SGS sarcomatous components remain unexplored. Herein, we investigated the clonal origin of SGS in a patient with primary GBM progressing into SGS post-radiochemotherapy. METHODS: Somatic mutation profile in GBM and SGS was examined using whole-genome sequencing and deep-whole-exome sequencing. Mutation signatures were characterized to investigate relationships between radiochemotherapy and SGS pathogenesis. RESULTS: A mutation cluster containing two founding mutations in tumor-suppressor genes NF1 (variant allele frequency [VAF]: 50.0% in GBM and 51.1% in SGS) and TP53 (VAF: 26.7% in GBM and 50.8% in SGS) was shared in GBM and SGS. SGS exhibited an overpresented C>A (G>T) transversion (oxidative DNA damage signature) but no signature 11 mutations (alkylating-agents - exposure signature). Since radiation induces DNA lesions by generating reactive oxygen species, the mutations observed in this case of SGS were likely the result of radiotherapy rather than chemotherapy. CONCLUSIONS: Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS.

Comprehensive Analysis of Differentially Expressed lncRNAs miRNAs and mRNA and Their ceRNA Network of Patients With Rare-Earth Pneumoconiosis.

Rare-earth pneumoconiosis (REP) is the main occupational disease of rare earth exposed workers and there is no specific treatment. In this study, we performed high-throughput sequencing on the plasma of nine REP to describe and analyze the expression profiles of long non-coding RNA (lncRNA), micro RNA (miRNA) and mRNA and investigate their regulatory networks. Our results identified a total of 125 lncRNAs, 5 miRNAs, and 82 mRNAs were differentially expressed in the plasma of patients with REP. Furthermore, Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the differentially expressed non-coding RNAs (ncRNA). We found the differential expression of ncRNA are mainly related to the response of cells to stimulation, Hedgehog signaling pathway and so on. We also constructed lncRNA-miRNA-mRNA networks to further explore their underlying mechanism and possible relationships in REP. We found that in the competitive endogenous RNA (ceRNA) networks, lncRNA acts as a sponge of miRNA to regulate the target gene. The expression results were verified by qRT-PCR and the protein interaction networks of differentially expressed genes were constructed via the STRING database. OncoLnc online platform was used to do the lung cancer survival analysis among the top five mRNA analyzed by Protein-protein interaction (PPI) network analysis. We found miR-16-2-3p may used as biomarker for REP, because it is closely related to the occurrence and prognosis of REP through inflammatory reaction and in lung squamous cell carcinoma, its expression levels were positively correlated with the overall survival rate of patients.

Impact of beta-2 microglobulin expression on the survival of glioma patients via modulating the tumor immune microenvironment.

AIMS: High immune cell infiltration in gliomas establishes an immunosuppressive tumor microenvironment, which in turn promotes resistance to immunotherapy. Hence, it is important to identify novel targets associated with high immune cell infiltration in gliomas. Our previous study showed that serum levels of beta-2 microglobulin (B2M) in lower-grade glioma patients were lower than those in glioblastoma patients. In the present study, we focused on exploring the roles of B2M in glioma immune infiltration. METHODS: A large cohort of patients with gliomas from the TCGA, CGGA, and Gravendeel databases was included to explore differential expression patterns and potential roles of B2M in gliomas. A total of 103 glioma tissue samples were collected to determine the distributions of B2M protein levels by immunofluorescent assays. Kaplan-Meier survival analysis and meta-analysis were used for survival analysis. GO(Gene-ontology) enrichment analysis, co-expression analysis, KEGG(Kyoto Encyclopedia of Genes and Genomes) pathway analysis, and immune infiltration analysis were performed to explore roles and related mechanisms of B2M in glioma. RESULTS: We found that both B2M mRNA and protein levels were abnormally upregulated in glioma samples compared with those from normal brain tissue. B2M expression was correlated with tumor grade and was downregulated in IDH1 mutant samples. Furthermore, B2M was a moderately sensitive indicator for predicting the mesenchymal molecular subtype of gliomas. Interestingly, glioma patients with lower B2M expression had remarkably longer survival times than those with higher B2M expression. Moreover, meta-analysis showed that B2M was an independent predictive marker in glioma patients. The results of GO enrichment analysis revealed that B2M contributed to immune cell infiltration in glioma patients. In addition, results of KEGG pathway analysis and co-expression analysis suggested that B2M may mediate glioma immune infiltration via chemokines. CONCLUSIONS: We conclude that B2M levels are critical for the survival times of glioma patients, at least in part due to mediating high immune infiltration.