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BackgroundTumor initiation and metastasis influence tumor immune exclusion and immunosuppression. Long non-coding RNA (lncRNA) LINC01614 is associated with the prognosis and metastasis of several cancers. However, the relationship between LINC01614 and cancer immune infiltration and the biofunction of LINC01614 in head and neck squamous cell carcinoma (HNSC) remain unclear.MethodsThe Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets were used to analyze the expression difference and diagnostic value of LINC01614 in normal and tumor tissues. The correlation of pan-cancer prognosis and tumor stage of LINC01614 was analyzed based on the TCGA database. The pan-cancer association of LINC01614 expression with the tumor microenvironment (TME) including immune infiltration, expression of immune-related genes, and genomic instability parameters, was analyzed using the Spearman correlation method. The correlation between LINC01614 and tumor stemness evaluation indicators, RNA methylation-related genes, and drug resistance was also analyzed. The functional analysis of LINC01614 was performed using the clusterProfiler R package. The protein–protein interaction (PPI) network and ceRNA network of LINC01614 co-expressed genes and miRNA were constructed and visualized by STRING and Cytoscape, respectively. Finally, the cell location and influence of LINC01614 on cell proliferation and metastasis of HNSC cell lines were evaluated using FISH, CCK-8, wound-healing assay, and transwell assay.ResultsLINC01614 was found to be overexpressed in 23 cancers and showed a highly sensitive prediction value in nine cancers (AUC >0.85). LINC01614 dysregulation was associated with tumor stage in 12 cancers and significantly influenced the survival outcomes of 26 cancer types, with only Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC), uterine corpus endometrial carcinoma (UCEC), and bladder urothelial carcinoma (BLCA) showing a benign influence. LINC01614 was also associated with immune cell infiltration, tumor heterogeneity, cancer stemness, RNA methylation modification, and drug resistance. The potential biological function of LINC01614 was verified in HNSC, and it was found to play important roles in proliferation, immune infiltration, immunotherapy response, and metastasis of HNSC.ConclusionLINC01614 may serve as a cancer diagnosis and prognosis biomarker and an immunotherapy target for specific cancers.

Background: Mitochondrial redox imbalance underlies the pathophysiology of type2 diabetes mellitus (T2DM), and is closely related to tissue damage and dysfunction. Studies have shown the beneficial effects of dietary strategies that elevate β-hydroxybutyrate (BHB) levels in alleviating T2DM. Nevertheless, the role of BHB has not been clearly elucidated. Methods: We performed a spectral study to visualize the preventive effects of BHB on blood and multiorgan mitochondrial redox imbalance in T2DM mice via using label-free resonance Raman spectroscopy (RRS), and further explored the impact of BHB therapy on the pathology of T2DM mice by histological and biochemical analyses. Findings: Our data revealed that RRS-based mitochondrial redox states assay enabled clear and reliable identification of the improvement of mitochondrial redox imbalance by BHB, evidenced by the reduction of Raman peak intensity at 750 cm−1, 1128 cm−1 and 1585 cm−1 in blood, tissue as well as purified mitochondria of db/db mice and the increase of tissue mitochondrial succinic dehydrogenase (SDH) staining after BHB treatment. Exogenous supplementation of BHB was also found to attenuate T2DM pathology related to mitochondrial redox states, involving organ injury, blood glucose control, insulin resistance and systemic inflammation. Interpretation: Our findings provide strong evidence for BHB as a potential therapeutic strategy targeting mitochondria for T2DM.

Abstract The occurrence of osteoarthritis (OA) is highly correlated with the reduction of joint lubrication performance, in which persistent excessive inflammation and irreversible destruction of cartilage dominate the mechanism. The inadequate response to monotherapy methods, suboptimal efficacy caused by undesirable bioavailability, short retention, and lack of stimulus-responsiveness, are few unresolved issues. Herein, we report a pH-responsive metal-organic framework (MOF), namely, MIL-101-NH2, for the co-delivery of anti-inflammatory drug curcumin (CCM) and small interfering RNA (siRNA) for hypoxia inducible factor (HIF-2α). CCM and siRNA were loaded via encapsulation and surface coordination ability of MIL-101-NH2. Our vitro tests showed that MIL-101-NH2 protected siRNA from nuclease degradation by lysosomal escape. The pH-responsive MIL-101-NH2 gradually collapsed in an acidic OA microenvironment to release the CCM payloads to down-regulate the level of pro-inflammatory cytokines, and to release the siRNA payloads to cleave the target HIF-2α mRNA for gene-silencing therapy, ultimately exhibiting the synergetic therapeutic efficacy by silencing HIF-2α genes accompanied by inhibiting the inflammation response and cartilage degeneration of OA. The hybrid material reported herein exhibited promising potential performance for OA therapy as supported by both in vitro and in vivo studies and may offer an efficacious therapeutic strategy for OA utilizing MOFs as host materials.

[Introduction] With the rapid expansion of the city, underground municipal engineering construction has been widely used. Underground municipal engineering has special requirements such as complex construction technology, wide space volume and installation limitation of process equipment. [Method] According to the above characteristics, combining with the relevant specification requirements and engineering examples, this paper expounded the current underground municipal engineering design of power supply and distribution system and automatic control design. [Result] The design ideas in load grade determination, energy saving optimization design, intelligent control, energy consumption management and other aspects are put forward, and some ideas and suggestions in energy saving, new energy are also put forward. [Conclusion] The main points of electrical design of underground municipal engineering are discussed and summarized, which can provide some reference for similar design.

Genetic lineage tracing is indispensable to unraveling the origin, fate, and plasticity of cells. However, the intrinsic leakiness in the CreER-loxP system raises concerns on data interpretation. Here, we reported the generation of a novel dual inducible CreER-loxP system with superior labeling characteristics. This two-component system consists of membrane localized CreER (mCreER: CD8α-FRB-CS-CreER) and TEV protease (mTEVp: CD8α-FKBP-TEVp), which are fusion proteins incorporated with the chemically induced dimerization machinery. Rapamycin and tamoxifen induce sequential dimerization of FKBP and FRB, cleavage of CreER from the membrane, and translocation into the nucleus. The labeling leakiness in Ad293 cells reduced dramatically from more than 70% to less than 5%. This tight labeling feature depends largely on the association of mCreER with HSP90, which conceals the TEV protease cutting site between FRB and CreER and thus preventing uninduced cleavage of the membrane-tethering CreER. Membrane-bound CreER also diminished significantly cytotoxicity. Our studies showed mCreER under the control of the rat insulin promoter increased labeling specificity in MIN6 islet beta-cells. Viability and insulin secretion of MIN6 cells remained intact. Our results demonstrate that this novel system can provide more stringent temporal and spatial control of gene expression and will be useful in cell fate probing.

Timely detection of fabric defects is crucial for improving fabric quality and reducing production losses for companies. Traditional methods for detecting fabric defects face several challenges, including low detection efficiency, poor accuracy, and limited types of detectable defects. To address these issues, this paper chose the YOLOv8n model for continuous iteration enhancement in order to improve its detection performance. First, multiscale feature fusion was realized by the Bi-directional Feature Pyramid Network (BiFPN). Second, the Shuffle Attention Mechanism (SA) is introduced to optimize feature classification. Finally, the Global Attention Mechanism (GAM) was used to improve global detection accuracy. Empirical findings demonstrated the improved model's efficacy, attaining a test set mean average precision (mAP) value of 96.6%, which is an improvement of 3.6% compared to the original YOLOv8n. This validates that YOLO-BGS excels in detecting textile defects. It effectively locates these defects, minimizes resource waste, and fosters sustainable production practices. [ABSTRACT FROM AUTHOR]

The porosity of the cold sprayed deposits reflects the deformation degree of the sprayed particles and the bonding degree between them, which has an important influence on the deposit properties such as hardness, elastic modulus, friction and wear performance, corrosion resistance, fatigue property and so on. Hence, the porosity of deposits is very important for evaluating the comprehensive properties of deposits and optimizing the cold spraying process parameters, and it is one of the important indicators to evaluate the quality of deposits. Although previous review articles have summarized the influence of cold spraying process on the cold sprayed deposits performance, there were few review articles involving pores in cold sprayed deposits and their control methods. Referring to dozens of articles, this article aimed to review the formation of pores in cold sprayed deposits, the measurement methods, the influence factors and summarize the influence of porosity on the properties of deposits and the measures to reduce the porosity of deposits.

Graphene has excellent mechanical, electronic, thermal, magnetic and chemical and shielding performance, which presents great potential in the field of anti - corrosion. At present, there are two main ways in anti - corrosive application for grapheme: one is to act on the substrate directly, the other is as nano filler to modify the polymer coating. The comprehensive anti - corrosive performance of composite anti - corrosive coating produced by graphene and anti - corrosive polymer materials was greatly improved. In this paper, in the research field of composite anti - corrosive coating, the functional application of graphene in solvent and water - based epoxy resin anti - corrosive coating, polyurethane anti - corrosive coating and acrylic anti - corrosive coating was introduced. The status of research on graphene composite anti - corrosive coating at home and abroad in recent years were also summarized. Finally, the development prospect of graphene composite anti - corrosive coating was prospected.

Background: Pancreatic adenocarcinoma (PAAD) is one of the most aggressive and fatal gastrointestinal malignancies with high morbidity and mortality worldwide. Accumulating evidence has revealed the clinical significance of the interaction between the hypoxic microenvironment and cancer stemness in pancreatic cancer progression and therapies. This study aims to identify a hypoxia-stemness index-related gene signature for risk stratification and prognosis prediction in PAAD.Methods: The mRNA expression-based stemness index (mRNAsi) data of PAAD samples from The Cancer Genome Atlas (TCGA) database were calculated based on the one-class logistic regression (OCLR) machine learning algorithm. Univariate Cox regression and LASSO regression analyses were then performed to establish a hypoxia-mRNAsi-related gene signature, and its prognostic performance was verified in both the TCGA-PAAD and GSE62452 corhorts by Kaplan-Meier and receiver operating characteristic (ROC) analyses. Additionally, we further validated the expression levels of signature genes using the TCGA, GTEx and HPA databases as well as qPCR experiments. Moreover, we constructed a prognostic nomogram incorporating the eight-gene signature and traditional clinical factors and analyzed the correlations of the risk score with immune infiltrates and immune checkpoint genes.Results: The mRNAsi values of PAAD samples were significantly higher than those of normal samples (p < 0.001), and PAAD patients with high mRNAsi values exhibited worse overall survival (OS). A novel prognostic risk model was successfully constructed based on the eight-gene signature comprising JMJD6, NDST1, ENO3, LDHA, TES, ANKZF1, CITED, and SIAH2, which could accurately predict the 1-, 3-, and 5-year OS of PAAD patients in both the training and external validation datasets. Additionally, the eight-gene signature could distinguish PAAD samples from normal samples and stratify PAAD patients into low- and high-risk groups with distinct OS. The risk score was closely correlated with immune cell infiltration patterns and immune checkpoint molecules. Moreover, calibration analysis showed the excellent predictive ability of the nomogram incorporating the eight-gene signature and traditional clinical factors.Conclusion: We developed a hypoxia-stemness-related prognostic signature that reliably predicts the OS of PAAD. Our findings may aid in the risk stratification and individual treatment of PAAD patients.

Abstract Background Potocki–Shaffer syndrome (PSS) is a rare contiguous gene deletion syndrome marked by haploinsufficiency of genes in chromosomal region 11p11.2p12. Approximately 50 cases of PSS have been reported; however, a syndrome with a PSS-like clinical phenotype caused by 11p11.12p12 duplication has not yet been reported. Methods 11p11.12p12 duplication syndrome was identified and evaluated using a multidisciplinary protocol. Diagnostic studies included intelligence testing, thorough physical examination, electroencephalography (EEG), magnetic resonance imaging (MRI) of the brain, ultrasonography, biochemical tests and karyotype analysis. Next-generation sequencing analysis clarified the location of the chromosomal variations, which was confirmed by chromosome microarray analysis (CMA). Whole-exome sequencing (WES) was performed to exclude single nucleotide variations (SNVs). A wider literature search was performed to evaluate the correlation between the genes contained in the chromosomal region and clinical phenotypes. Results The proband was a 36-year-old mother with intellectual disability (ID) and craniofacial anomalies (CFA). She and her older son, who had a similar clinical phenotype, both carried the same 11p11.12p12 duplication with a copy number increase of approximately 10.5 Mb (chr11:40231033_50762504, GRCh37/hg19) in chromosome bands 11p11.12p12. In addition, she gave birth to a child with a normal phenotype who did not carry the 11p11.12p12 duplication. By literature research and DECIPHER, we identified some shared and some distinct features between this duplication syndrome and PSS. One or more of ALX4, SLC35C1, PHF21A and MAPK8IP1 may be responsible for 11p11.12p12 duplication syndrome. Conclusions We present the first report of 11p11.12p12 duplication syndrome. It is an interesting case worth reporting. The identification of clinical phenotypes will facilitate genetic counselling. A molecular cytogenetic approach was helpful in identifying the genetic aetiology of the patients and potential candidate genes with triplosensitive effects involved in 11p11.12p12 duplication.

Primary coenzyme Q10 deficiency-6 (COQ10D6), as a rare autosomal recessive disease caused by COQ6 mutations, is characterized by progressive infantile-onset nephrotic syndrome resulting in end-stage renal failure and sensorineural hearing loss. Here, we report two Chinese siblings with COQ10D6 who primarily presented with severe metabolic acidosis, proteinuria, hypoalbuminemia, growth retardation, and muscle hypotonia and died in early infancy. Using whole-exome sequencing and Sanger sequencing, we identified two rare recessive nonsense mutations in the COQ6 gene segregating with disease in affected family members: c.249C > G (p.Tyr83Ter) and c.1381C > T (p.Gln461Ter), resulting in two truncated protein products. Both mutations are located in a highly conserved area and are predicted to be pathogenic. Indeed, the death of our patients in early infancy indicates the pathogenicity of the p.Tyr83Ter and p.Gln461Ter variants and highlights the significance of the two variants for COQ6 enzyme function, which is necessary for the biosynthesis of coenzyme Q10. In conclusion, we discovered a novel compound heterozygous pathogenic variant of the COQ6 gene as a cause of severe COQ10D6 in the two siblings. Based on the clinical history and genetic characteristics of the patients, our cases expand the genotypic spectrum of COQ10D6 and highlight the heterogeneity and severity of clinical features associated with COQ6 mutations. For patients with clinical manifestations suggestive of COQ10D6, early testing for COQ6 mutations is beneficial for disease diagnosis and therapeutic interventions as well as disease prevention in future generations.