The potential value of oral microbial signatures for prediction of oral squamous cell carcinoma based on machine learning algorithms.

OBJECTIVE: This study aimed to explore the potential predictive value of oral microbial signatures for oral squamous cell carcinoma (OSCC) risk based on machine learning algorithms. METHODS: The oral microbiome signatures were assessed in the unstimulated saliva samples of 80 OSCC patients and 179 healthy individuals using 16S rRNA gene sequencing. Four different machine learning classifiers were used to develop prediction models. RESULTS: Compared with control participants, OSCC patients had a higher microbial dysbiosis index (MDI, p < 0.001). Among four machine learning classifiers, random forest (RF) provided the best predictive performance, followed by the support vector machines, artificial neural networks and naive Bayes. After controlling the potential confounders using propensity score matching, the optimal RF model was further developed incorporating a minimal set of 20 bacteria genera, exhibiting better predictive performance than the MDI (AUC: 0.992 vs. 0.775, p < 0.001). CONCLUSIONS: The novel MDI and RF model developed in this study based on oral microbiome signatures may serve as noninvasive tools for predicting OSCC risk.

Effect Analysis of the Venting Direction on Explosion Pressure in LPG Pipelines.

In order to study the effect of the venting direction on explosion pressure in liquefied petroleum gas pipelines, explosion accident scenarios are experimentally tested and numerically simulated in a pipeline model with different explosion venting directions. In addition, the effect characteristic is analyzed through the pressure field varying with time and peak pressure varying with the distance. Results show that the pressure in the vertical branch decreases sharply, while the pressure in the horizontal branch does not show an obvious decrease with explosion venting of the vertical branch. However, the pressure decreases obviously in both branches with explosion venting of the horizontal branch, and the biggest reduction of peak pressure of monitoring points is 73.55% compared with that without venting. In addition, large areas of negative pressure appear in both branches with explosion venting of the vertical branch; however, a large area of negative pressure area appears in the horizontal branch with explosion venting of the horizontal branch. What is more, the arrival time of peak pressure in the main pipe of the explosion pipeline is significantly reduced with explosion venting, which is caused by the different generation ways of peak pressure. The effect analysis result of the venting direction on explosion pressure could aid the optimal layout design of LPG pipelines with the location of venting and important facilities as well as with the selection of negative-pressure-resistant material and higher-accuracy sensors.

Research Progress on hCNT3 Structure/Function and Nucleoside Anticancer Drugs.

Membrane protein human concentrative nucleoside transporter 3 (hCNT3) can not only transport extracellular nucleosides into the cell but also transport various nucleoside-derived anticancer drugs to the focus of infection for therapeutic effects. Typical nucleoside anticancer drugs, including fludarabine, cladabine, decitabine, and clofarabine, are recognized by hCNT3 and then delivered to the lesion site for their therapeutic effects. hCNT3 is highly conserved during the evolution from lower to higher vertebrates, which contains scaffold and transport domains in structure and delivers substrates by coupling with Na+ and H+ ions in function. In the process of substrate delivery, the transport domain rises from the lower side of transmembrane 9 (TM9) in the inward conformation to the upper side of the outward conformation, accompanied by the collaborative motion of TM7b/ TM4b and hairpin 1b (HP1b)/ HP2b. With the report of a series of three-dimensional structures of homologous CNTs, the structural characteristics and biological functions of hCNT3 have attracted increasing attention from pharmacists and biologists. Our research group has also recently designed an anticancer lead compound with high hCNT3 transport potential based on the structure of 5-fluorouracil. In this work, the sequence evolution, conservation, molecular structure, cationic chelation, substrate recognition, elevator motion pattern and nucleoside derivative drugs of hCNT3 were reviewed, and the differences in hCNT3 transport mode and nucleoside anticancer drug modification were summarized, aiming to provide theoretical guidance for the subsequent molecular design of novel anticancer drugs targeting hCNT3.

Enhanced oxidative stress is associated with tissue neutrophilia and poor steroid response in chronic rhinosinusitis with nasal polyps.

Objective: To analyze the oxidative stress status and its association with tissue neutrophilia and oral steroid response in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Methods: The levels of total oxidant status (TOS) were detected in the sinonasal tissues by using specific assay kits. Tissue neutrophil was examined by immunohistochemical staining, and oxidant status index (OSI) was evaluated in polyps tissues, and the messenger RNA (mRNA) levels of superoxide dismutase 2 (SOD2), aldehyde dehydrogenase 1 (ALDH1A1), and microsomal glutathione S-transferase 1 (MGST1) were examined using quantitative real-time polymerase chain reaction in the sinonasal tissues. The receiver operating characteristics (ROCs) curve of ALDH1A1, MGST1, and SOD2 mRNA levels were evaluated to determine the steroid response of CRSwNP patients. Results: The levels of TOS and OSI were significantly higher in CRSwNP and CRSsNP than in normal controls, and OSI in polyps tissues was positively associated with tissue neutrophilia and poor steroid response. The ALDH1A1, MGST1, and SOD2 mRNA levels showed comparable accuracy as predictors of poor steroid response indicated by the area under the curve. Conclusion: These findings provided evidence that the increased level of oxidative stress contributes to enhanced tissue neutrophilia and poor steroid response in CRSwNP patients.

Potential of periosteal cells in bone and cartilage regeneration: a systematic review.

Introduction: The unavailability of adequate human primary cells presents multiple challenges in terms of bone and cartilage regeneration and disease modeling experiments in vitro. Periosteal cells (PCs), which represent promising skeletal stem cell sources, could be a promising strategy in tissue engineering. The present study aimed to summarize the characteristics of PCs to investigate the efficacy of these cells in bone and cartilage regeneration in different models, paying special attention to the comparison of bone marrow stromal cells (BMSCs). Methods: A comprehensive literature search was conducted in Embase, PubMed/MEDLINE, Web of Science, and Scopus for articles published in English until April 2023. Only original researches in which PCs were employed for bone or cartilage regeneration experiments were included. Results: A total of 9140 references were retrieved. After screening the results, 36 publications were considered to be eligible for inclusion in the present literature review. Overall, PCs demonstrated beneficial bone and cartilage regenerative efficacy compared to the bare scaffold since almost all included studies reported positive results. The 9 studies assessing the differences in bone formation capacity between PCs and BMSCs indicated that PCs exhibited stronger in vivo osteogenic differentiation capabilities compared to BMSCs, while the other study demonstrated stronger chondrogenic potential of BMSCs. Discussion: PCs demonstrated beneficial to bone regenerative efficacy compared to the bare scaffold with a low risk of most studies included. However, the cartilage formation capacity of BMSCs still needs to be investigated due to the limited research available and the certain risk of bias. PCs exhibited higher osteogenic capabilities compared to BMSCs in combination with various scaffolds in vivo with good evidence. Further researches are needed to elucidate the comparative benefits of cartilage regeneration. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023411522, CRD42023411522.

Accuracy of intraoral scanning versus conventional impressions for partial edentulous patients with maxillary defects.

This study aimed to evaluate the accuracy of digital dental impressions obtained by intraoral scanning (IOS) for partial edentulous patients with maxillary defects by comparing them with conventional impression techniques. Ten subjects underwent an experimental procedure where three ceramic blocks were affixed to the healthy palate mucosa. Digital dental impressions were captured using IOS and subsequently imported into software. Conventional impressions obtained by silicone rubber were also taken and scanned. Linear distance and best-fit algorithm measurements were performed using conventional impression techniques as the reference. Twenty impressions were analyzed, which included 30 pairs of linear distances and 10 best-fit algorithm measurements. Regarding linear distance, paired two-sample t-test demonstrated no significant differences between IOS and model scanning in groups A and C, whereas significant differences were found in group B (P < 0.05). Additionally, ANOVA revealed significant differences among the groups (P < 0.05). No significant differences were found for the best-fit algorithm measurement of the dentition. IOS can provide accurate impressions for partial edentulous patients with maxillary defects and its accuracy was found to be comparable with conventional impression techniques. A functional impression may be needed to ensure accurate reproduction of soft and hard tissues in defect or flap areas.

Identification of a Seed Vigor-Related QTL Cluster Associated with Weed Competitive Ability in Direct-Seeded Rice (Oryza Sativa L.).

Direct seeding of rice (Oryza sativa L.) is a low-labor and sustainable cultivation method that is used worldwide. Seed vigor and early vigor are important traits associated with seedling stand density (SSD) and weed competitive ability (WCA), which are key factors in direct-seeded rice (DSR) cultivation systems. Here, we developed a set of chromosome segment substitution lines with Xiushui134 as receptor parent and Yangdao6 as donor parent and used these lines as a mapping population to identify quantitative trait loci (QTLs) for seed vigor, which we evaluated based on germinability-related indicators (germination percentage (GP), germination energy (GE), and germination index (GI)) and seedling vigor-related indicators (root number (RN), root length (RL), and shoot length (SL) at 14 days after imbibition) under controlled conditions in an incubator. Ten QTLs were detected across four chromosomes, of which a cluster of QTLs (qGP11, qGE11, qGI11, and qRL11) co-localized on Chr. 11 with high LOD values (12.03, 8.13, 7.14, and 8.75, respectively). Fine mapping narrowed down the QTL cluster to a 0.7-Mb interval between RM26797 and RM6680. Further analysis showed that the QTL cluster has a significant effect (p < 0.01) on early vigor under hydroponic culture (root length, total dry weight) and direct seeding conditions (tiller number, aboveground dry weight). Thus, our combined analysis revealed that the QTL cluster influenced both seed vigor and early vigor. Identifying favorable alleles at this QTL cluster could facilitate the improvement of SSD and WCA, thereby addressing both major factors in DSR cultivation systems.

Characterization and potential of periosteum-derived cells: an overview.

As a thin fibrous layer covering the bone surface, the periosteum plays a significant role in bone physiology during growth, development and remodeling. Over the past several decades, the periosteum has received considerable scientific attention as a source of mesenchymal stem cells (MSCs). Periosteum-derived cells (PDCs) have emerged as a promising strategy for tissue engineering due to their chondrogenic, osteogenic and adipogenic differentiation capacities. Starting from the history of PDCs, the present review provides an overview of their characterization and the procedures used for their isolation. This study also summarizes the chondrogenic, osteogenic, and adipogenic abilities of PDCs, serving as a reference about their potential therapeutic applications in various clinical scenarios, with particular emphasis on the comparison with other common sources of MSCs. As techniques continue to develop, a comprehensive analysis of the characterization and regulation of PDCs can be conducted, further demonstrating their role in tissue engineering. PDCs present promising potentials in terms of their osteogenic, chondrogenic, and adipogenic capacities. Further studies should focus on exploring their utility under multiple clinical scenarios to confirm their comparative benefit over other commonly used sources of MSCs.

A Comprehensive Analysis of Clinical Crowns in Young of Han Nationality with Normal Occlusion Using Intraoral Scanning.

Background: The measurement and analysis of clinical crowns play a crucial role in stomatology, anthropology, and studies of genetic and environmental variables in oral and maxillofacial development. Purpose: The objective of the present study was to measure the parameters of clinical crowns of permanent dentition in youth of Han nationality using intraoral scanning and identify potential influencing factors. Materials and Methods: A total of 100 subjects (50 males and 50 females) of Han nationality aged 18-24 with normal occlusion were selected. An intraoral scanner was used to obtain the digital dental impressions, and Materialise Magics 21 software was used to measure the mesiodistal diameter (MDD), buccolingual diameter (BLD), height, mesiodistal angle (MDA), and vestibulo-oral angle (VOA) of clinical crowns. The central height was calculated based on the height of clinical crowns. SPSS 27.0 software was used for statistical analysis. The two-independent-samplet-test was used to assess discrepancies in clinical crowns between males and females. The paired t-test was used to determine differences between antimetric pairs of clinical crowns within the same arch. The repeatability of intraoral scanning was tested using the paired t-test between two measurements at one-month intervals. The overall estimated effect was considered significant where P < 0.05. Results: The MDD, BLD, height, MDA, and VOA of clinical crowns in the youth of Han nationality were measured, and the central height was calculated. No significant difference was found in terms of MDA and VOA between genders and antimetric pairs within the same arch. Regarding the distance parameters, the MDD, BLD, and height of clinical crowns in males were significantly larger than those in females (MDD: U1, U3, U7, L2, L3, L6, and L7: P < 0.01; BLD: U1: P=0.02; U3-U7 and L1-L7: P < 0.01; height: U2: P=0.03; and U1, U3-U7, and L3-L7: P < 0.01). No significant difference was found in clinical crowns between antimetric pairs within the same arch. Intraoral scanning demonstrated good repeatability in the measurement of clinical crowns. Conclusions: Apart from MDA and VOA, the parameters of clinical crowns in males were significantly larger than in females. Antimetric pairs of clinical crowns within the same arch demonstrated similar tooth dimensions. In future clinical practice and scientific research in the oral and maxillofacial region, a comprehensive design of sexual and ethnic characteristics should be considered.

1,3-Pentadiene-Assistant Living Anionic Terpolymerization: Composition Impact on Kinetics and Microstructure Sequence Primary Analysis.

The combination of a living anionic technology and a unique alternating strategy provided an exciting opportunity to prepare novel and well-defined poly(1,3-pentadiene-co-syrene-co-1,1-diphenylethylene) resins consisting of three alternating sequences of modules (A/B/C zwitterions). "A" being Styrene (St)/1,3-pentadiene (PD), "B" being diphenylethylene (DPE)/PD, "A" being DPE/St, respectively, A wide composition range of new polyolefin resins, i.e., poly (A-co-B), poly (A-co-C), and poly (B-co-C), with controlled molecular weight and very narrow molecular weight and composition distributions have been prepared by a one-pot living characteristic method. In the section of kinetic analysis, the terpolymer yields and kinetic parameters were strongly dependent on the feed/comonomer ratio as well as the content of the alternating structure. The competition copolymerization behaviors of A/B, B/C, and A/C were studied in detail in this work. By contrast, the microstructure and the thermal property of the resulting terpolymer were investigated via Nuclear magnetic resonance (NMR) and Differential scanning calorimetry (DSC) analysis. The results of 1H NMR tracking the change of [Aromatic ring]/[C=C] value indicated the distinctive copolymer-ization behavior of the selective "alternating-modules". The glass transition temperature (Tg) was very sensitive to the terpolymer composition. By contrast to poly(A-ran-B) with only one obvious Tg, there were two Tgs in the A/C and B/C copolymerization cases. Moreover, the desirable high Tg ~ 140 °C resin was limited to the terpolymers with up to 50 mol % DPE. Finally, the "ABC-X" mechanism was proposed to interpret the unique terpolymerization behavior, which belongs to the classical "bond-forming initiation" theory.

Increased IL-1α expression in chronic rhinosinusitis with nasal polyps.

PURPOSE: To examine whether and how interleukin (IL)-1α is involved in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Nasal polyp (NP) and control tissues were collected from CRSwNP patients and control subjects. The expression of IL-1α and other proinflammatory cytokines (IL-1ß, IL-8 and IL-13, etc.), as well as neutrophil and eosinophil accumulation, were examined in sinonasal tissues using immunohistochemical (IHC), immunofluorescent (IF) staining, qPCR, and Luminex, respectively. Moreover, the regulation of IL-1α expression and its effects on other proinflammatory cytokines were evaluated in cultured nasal epithelial cells (NECs). RESULTS: The mRNA and protein levels of IL-1α were significantly higher in NP tissues compared to that in control tissues. IL-1α in polyp tissues was mainly located in epithelial cells and neutrophils. Polyps IL-1α level was significantly associated with IL-8, IL-1ß, IL-6, IL-4 and IL-13 production, as well as tissue neutrophil infiltration. Moreover, poly (I:C), lipopolysaccharides, Flagellin, R848 and cytokines (IL-4, IL-5, and IL-13) significantly increased the expression of IL-1α in cultured NECs in vitro, and recombinant IL-1α significantly promoted production of IL-8 and CXCL1 in cultured NECs. CONCLUSIONS: These findings provided the evidence that IL-1α were significantly increased in NP tissues, which may contribute to tissue neutrophilia in CRSwNP patients in China.

Two novel phosphorus/potassium-degradation bacteria: Bacillus aerophilus SD-1/Bacillus altitudinis SD-3 and their application in two-stage composting of corncob residue.

For effective utilization of corncob residue to realize green circular production, using composting to obtain a high-quality and low-cost biomass fertilizer has become a very important transformation avenue. In this paper, two novel phosphorus/potassium-degradation bacterial strains were isolated from tobacco straw and identified as Bacillus aerophilus SD-1/Bacillus altitudinis SD-3 (abbreviated as SD-1/SD-3). These identified two novel bacteria SD-1/SD-3 show that the soluble phosphorus content of SD-1/SD-3 reached 360.89 mg L-1/403.56 mg L-1 in the shake flask test, and the mass concentration of soluble potassium is 136.56 mg L-1/139.89 mg L-1. In addition, the Laccase (Lac), Lignin peroxidase (LiP), and Manganese peroxidase (MnP) activities of SD-1 and SD-3 are 54.45 U L-1/394.84 U L-1/222.79 U L-1 and 46.27 U L-1/395.26 U L-1/203.98 U L-1 respectively, with the carboxy-methyl cellulase (CMCase) of 72.07 U mL-1 and 52.69 U mL-1. Meanwhile, the effects of three different combinations of cultures, i.e., no inoculation (K1), inoculation of SD-1/SD-3 on day 21 (K2) and on day 0 (G) are investigated to understand the influence on the degradation degree of corncob residue compost. The results of K2 compost treatment showed that the effective P/K content increased nearly 3.1/2.4 times, the degradation of cellulose/lignin was 49.1/68.0%, and the germination rate was 110.23%, which were higher than other experiment groups K1/G. In conclusion, knowledge of this paper will be very useful for the industrial sector for the treatment of complex corncob residue.

The global, regional, and national burden of nasopharyngeal carcinoma and its attributable risk factors in 204 countries and territories, 1990-2019.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is uncommon in most areas of the world but poses a significant public health burden in endemic regions. OBJECTIVES: We provide an overview of the most recent global epidemiology of nasopharyngeal cancer (NPC). METHODS: We estimated the burden of NPC in 204 countries and territories by age, sex, and Socio-Demographic Index (SDI) from 1990 to 2019. RESULTS: At the GBD regional level, the most severe age-standardized incidence in 2019 occurred in East Asia. From 1990 to 2019, the East Asia and High-income Asia Pacific had the greatest increase in percentage in age-standardized incidence. Central Asia and the Caribbean had the greatest increase in percentage in age-standardized disability-adjusted life-years (DALY) and death rates. At the national level, Cabo Verde, Romania, and the Cyprus reported the largest percentage increases in the age-standardized incidence. Cabo Verde, Romania, and Jamaica reported the largest increases in the age-standardized DALY and death rates. CONCLUSIONS: The global age-standardized incidence of NPC increased globally between 1990 and 2019, especially in the East Asia.

Expression profile and prognostic value of CXCR family members in head and neck squamous cell carcinoma.

BACKGROUND: CXC chemokine receptor gene family consists of seven well-established members which are broadly involved in biological functions of various cancers. Currently, limited studies have shed light on the expression profile of CXCR family members (CXCRs), as well as their prognostic value, in head and neck squamous cells carcinoma (HNSCC). METHODS: The data for this study were retrieved from the Cancer Genome Atlas database and other publicly available databases, including gene expression, methylation profiles, clinical information, immunological features, and prognoses. The expression pattern and prognostic values of CXCRs were identified, and the potential mechanism underlying CXCRs function in HNSCC was investigated by gene set enrichment analysis (GSEA). RESULTS: CXCRs were differentially expressed in HNSCC. As shown by Kaplan-Meier analysis, high CXCR3-6 expression was significantly associated with better prognostic outcomes of HNSCC patients, including overall survival and progression-free survival. According to the results of univariate and multivariate Cox proportional risk regression analysis, it was demonstrated that upregulation of CXCR3-6 was an independent factor for better prognosis, while the two other clinical features, age and stage, were factors for worse prognosis. A significant positive correlation between CXCR3-6 and tumor-infiltrated immune cells was revealed by results from Tumor Immune Estimation Resource and CIBERSORT analysis database. The main involvement of CXCRs in immune and inflammatory responses was further confirmed by GSEA. CONCLUSIONS: Overall, this study provided a rationale for targeting CXCRs as a promising therapeutic strategy of HNSCC.

The Comparison of PCR Kits for the Detection of Erythrocytic Parasites on Filter Paper.

Dried blood spot (DBS) based PCR was considered an inexpensive and feasible method for detecting pathogens in the blood. The DBS carrier filter paper and PCR kits are crucial for accurate diagnosis. We evaluated 4 types of filter papers and 20 PCR kits for DBS samples. The PCR detecting Plasmodium results showed that the minimum detection limit of the 4 filter papers was 1 × 102 parasites/µL, and the positive rates of 20 PCR kits ranged from 0% to 100%. PCR results were satisfactory for detecting Plasmodium falciparum (P. falciparum) and Plasmodium. vivax (P. vivax) in archived DBS samples and Babesia gibsoni (B. gibsoni) in fresh pet DBS samples. Our results provided a useful reference for the detection of blood pathogens with DBS samples and direct PCR, especially for screening the cost-efficacy combination of filter paper and PCR kit in resource-limited areas.

Combined Exposure to 33 Trace Elements and Associations With the Risk of Oral Cancer: A Large-Scale Case-Control Study.

Background: Trace elements exist widely in the natural environment and mostly enter the human body through drinking water or various types of food, which has raised increasing health concerns. Exposure to a single or a few trace elements has been previously reported to be associated with oral cancer risk, but studies on other elements and combined effects are limited. This study aimed to comprehensively evaluate the independent and joint effects of 33 trace elements on oral cancer risk. Methods: The concentrations of 33 trace elements from the serum samples of 463 cases and 1,343 controls were measured using inductively coupled plasma mass spectrometry (ICP-MS). Propensity score matching was used to minimize the impact of potential confounders. Conditional logistic regression was utilized to evaluate the association of each element individually with oral cancer risk. Quantile g-computation and Bayesian kernel machine regression (BKMR) models were used to assess the joint effect of the overall element mixture and interactions. Results: In single-element models, essential elements (Cu, Se, Zn, Sr, and Cr) and non-essential elements (As, Li, Th, Ce, Ti, and Sc) showed significant association with oral cancer risk. In multiple-element models, a quartile increase in overall non-essential elements was observed for a significant inverse association with oral cancer risk (ß = -3.36, 95% CI: -4.22 to -2.51). The BKMR analysis revealed a potential beneficial joint effect of essential metals on the risk of oral cancer. Among these, higher levels of serum Zn and V exhibited an adverse effect, while serum Sr, Se, and Cu displayed favorable effects when all other essential elements were fixed at 25th or 50th percentiles. Of note, Se performed complex interactions among essential metals. As for non-essential elements, there were greater effect estimates for serum Th, Li, and Y when all other elements were held at the 75th percentile. Conclusion: This study provides supportive evidence that the overall mixture effect of essential and non-essential elements might be associated with oral cancer risk, especially for serum Zn, V, Cu, Sr, Se, Th, Li, and Y. Extensive prospective studies and other experiments are warranted to confirm our findings.

NGS4THAL, a One-Stop Molecular Diagnosis and Carrier Screening Tool for Thalassemia and Other Hemoglobinopathies by Next-Generation Sequencing.

Thalassemia is one of the most common genetic diseases and a major health threat worldwide. Accurate, efficient, and scalable analysis of next-generation sequencing (NGS) data is much needed for its molecular diagnosis and carrier screening. We developed NGS4THAL, a bioinformatics analysis pipeline analyzing NGS data to detect pathogenic variants for thalassemia and other hemoglobinopathies. NGS4THAL realigns ambiguously mapped NGS reads derived from the homologous Hb gene clusters for accurate detection of point mutations and small insertions/deletions. It uses a combination of complementary structural variant (SV) detection tools and an in-house database of control data containing specific SVs to achieve accurate detection of the complex SV types. Detected variants are matched with those in HbVar (A Database of Human Hemoglobin Variants and Thalassemia Mutations), allowing recognition of known pathogenic variants, including disease modifiers. Tested on simulation data, NGS4THAL achieved high sensitivity and specificity. For targeted NGS sequencing data from samples with laboratory-confirmed pathogenic Hb variants, it achieved 100% detection accuracy. Application of NGS4THAL on whole genome sequencing data from unrelated studies revealed thalassemia mutation carrier rates for Hong Kong Chinese and Northern Vietnamese that were consistent with previous reports. NGS4THAL is a highly accurate and efficient molecular diagnosis tool for thalassemia and other hemoglobinopathies based on tailored analysis of NGS data and may be scaled for population carrier screening.

CD3D: a prognostic biomarker associated with immune infiltration and immunotherapeutic response in head and neck squamous cell carcinoma.

Recent studies have demonstrated that CD3D activates T-cell-related signal transduction and is associated with the antitumor immune response in several cancers. This study explored the role of CD3D in head and neck squamous cell carcinoma (HNSCC). A total of 499 HNSCC tissues and 44 normal controls were acquired from The Cancer Genome Atlas as the training cohort. GSE65858 included 270 HNSCC patients and was obtained from the Gene Expression Omnibus database as the test cohort. Overall, 172 HNSCC patients were collected as the validation cohort. CD3D expression in the validation cohort was measured by quantitative real-time polymerase chain reaction. The Kaplan-Meier plot revealed that high CD3D expression was associated with longer overall survival in HNSCC patients. Univariate and multivariate analyses showed that CD3D expression was an independent prognostic factor for HNSCC patients, which was confirmed in the test cohort and validation cohort. Furthermore, GO, KEGG, and GSEA analyses revealed the association of CD3D with immune-related pathways. Subsequently, ESTIMATE analysis showed the association between CD3D and the tumor microenvironment, while ssGSEA showed a remarkable positive link between CD3D and immune-related functions. Multiple algorithms demonstrated that high CD3D expression was associated with more immune effector cell infiltration. Finally, the tumor immune dysfunction and exclusion (TIDE) score and immunophenoscore (IPS) showed that patients with high CD3D could benefit from immunotherapy. In summary, CD3D was an independent favorable prognostic biomarker and correlated with immune cell infiltration and immune-related function, as well as an efficient indicator of immunotherapy response for HNSCC patients.

Plasmodium infection suppresses colon cancer growth by inhibiting proliferation and promoting apoptosis associated with disrupting mitochondrial biogenesis and mitophagy in mice.

BACKGROUND: Colon cancer is a common gastrointestinal tumor with a poor prognosis, and thus new therapeutic strategies are urgently needed. The antitumor effect of Plasmodium infection has been reported in some murine models, but it is not clear whether it has an anti-colon cancer effect. In this study, we investigated the anti-colon cancer effect of Plasmodium infection and its related mechanisms using a mouse model of colon cancer. METHODS: An experimental model was established by intraperitoneal injection of Plasmodium yoelii 17XNL-infected erythrocytes into mice with colon cancer. The size of tumors was observed dynamically in mice, and the expression of Ki67 detected by immunohistochemistry was used to analyze tumor cell proliferation. Apoptosis was assessed by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and the expression of apoptosis-related proteins including Bax, Bcl-2, caspase-9, and cleaved caspase-3 was detected by western blot and immunohistochemistry, respectively. Transmission electron microscopy (TEM) was used to observe the ultrastructural change in colon cancer cells, and the expression of mitochondrial biogenesis correlative central protein, PGC-1α, and mitophagy relevant crucial proteins, PINK1/Parkin, were detected by western blot. RESULTS: We found that Plasmodium infection reduced the weight and size of tumors and decreased the expression of Ki67 in colon cancer-bearing mice. Furthermore, Plasmodium infection promoted mitochondria-mediated apoptosis in colon cancer cells, as evidenced by the increased proportion of TUNEL-positive cells, the upregulated expression of Bax, caspase-9, and cleaved caspase-3 proteins, and the downregulated expression of Bcl-2 protein. In colon cancer cells, we found destroyed cell nuclei, swollen mitochondria, missing cristae, and a decreased number of autolysosomes. In addition, Plasmodium infection disturbed mitochondrial biogenesis and mitophagy through the reduced expression of PGC-1α, PINK1, and Parkin proteins in colon cancer cells. CONCLUSIONS: Plasmodium infection can play an anti-colon cancer role in mice by inhibiting proliferation and promoting mitochondria-mediated apoptosis in colon cancer cells, which may relate to mitochondrial biogenesis and mitophagy.

The Expression Profile, Clinical Application and Potential Tumor Suppressing Mechanism of hsa_circ_0001675 in Head and Neck Carcinoma.

Purpose: This study sought to identify circular RNAs (circRNA) that participate in the regulation of head and neck cancer (HNC), analyze their clinical application, and predict their molecular mechanism during HNC. Materials and Methods: High-throughput sequencing was used to analyze circRNA expression in 18 matched HNC and adjacent normal tissues. Target circRNAs with significantly differential expression were obtained. In 103 HNC and adjacent normal tissues, real-time fluorescent quantitative PCR (qRT-PCR) was used to verify the differential expression of target circRNAs. This data was combined with clinicopathological information to analyze the diagnostic value of target circRNA. Bioinformatics was used to find target circRNAs that acted as competitive endogenous RNA (ceRNA) and construct a circRNA-miRNA-mRNA regulatory network. mRNA expression was verified by immunohistochemistry (IHC). Results: A total of 714 differentially expressed circRNAs were detected in HNC, and the low expression of hsa_circ_0001675 was particularly significant (fold change [FC] = -4.85, P = 6.305E-05). hsa_circ_0001675 had significantly lower expression in HNC than in normal tissue (P < 0.01). Low hsa_circ_0001675 expression was positively associated with tumor invasion and clinical staging (P < 0.05), and its area under the ROC curve (AUC) was 0.7776. Low hsa_circ_0001675 expression also correlated with the overall survival (OS) rate and the progression-free survival (PFS) rate of HNC patients (P < 0.001). Bioinformatics was used to construct a ceRNA network of hsa_circ_0001675 with six differentially expressed miRNAs (hsa-miR-330-5p, hsa-miR-498, hsa-miR-532-3p, hsa-miR-577, hsa-miR-1248, and hsa-miR-1305) and 411 differentially expressed mRNAs and found that the neuroactive ligand-receptor interaction, and the cAMP and calcium signaling pathways were particularly enriched. Further bioinformatics and IHC analysis showed that miR577/TESC is the likely downstream signaling pathway for hsa_circ_0001675. Conclusion: This study showed that hsa_circ_0001675 is downregulated in HNC and could be an effective biomarker for HNC diagnosis. In addition, hsa_circ_0001675 may have a potential ceRNA mechanism and suppress HNC disease progression through the hsa_circ_0001675-miRNA-mRNA axis.