Quantitative response of the spatial distribution of diesel oil to freezing and thawing temperatures in groundwater.

The mobilization and redistribution of organic contaminants in groundwater is the basis and key to explore its dynamic evolution and appropriate remediation. The naturally occurring diametrical temperature gradient during freezing and thawing cycle leads to distinct behaviors of organic contaminants in groundwater. In this study, the pore-scale distribution of diesel oil in the porous media was quantitatively divided into capillary fluid state (CFS) and free fluid state (FFS) based on multiphase flow dynamics, employing low-field nuclear magnetic resonance (LF-NMR) technology. The pore-scale distribution of diesel oil depends not only on the freezing and thawing cycle but also on the temperature gradient according to LF-NMR results. The content of diesel oil in the CFS generally increases with a positive temperature gradient (e.g. freezing) compared to a negative temperature gradient (e.g. thawing), while the content of diesel oil in the FFS generally decreases. This dependence of the temperature gradient on pore-scale distribution of the diesel oil is positively correlated with the particle size of the porous medium. Furthermore, the pore-scale distribution of the diesel oil during the freezing and thawing cycle is influenced by the kinematic viscosity of the diesel oil. There is an exponential relationship between the diesel oil content and the kinematic viscosity, independent of the freezing or thawing process. During the freezing process, the diesel oil migrates from FFS to CFS, while this migration is reversed during the thawing process. The reverse migration of the diesel oil between the freezing and thawing processes leads to a spatial redistribution of the diesel oil, which is controlled by both the fluid energy and the capillary force. The present work provide meaningful guidance for the remediation of groundwater contamination in cold regions.

OH2 oncolytic virus: A novel approach to glioblastoma intervention through direct targeting of tumor cells and augmentation of anti-tumor immune responses.

Glioblastoma (GBM), the deadliest central nervous system cancer, presents a poor prognosis and scant therapeutic options. Our research spotlights OH2, an oncolytic viral therapy derived from herpes simplex virus 2 (HSV-2), which demonstrates substantial antitumor activity and favorable tolerance in GBM. The extraordinary efficacy of OH2 emanates from its unique mechanisms: it selectively targets tumor cells replication, powerfully induces cytotoxic DNA damage stress, and kindles anti-tumor immune responses. Through single-cell RNA sequencing analysis, we discovered that OH2 not only curtails the proliferation of cancer cells and tumor-associated macrophages (TAM)-M2 but also bolsters the infiltration of macrophages, CD4+ and CD8+ T cells. Further investigation into molecular characteristics affecting OH2 sensitivity revealed potential influencers such as TTN, HMCN2 or IRS4 mutations, CDKN2A/B deletion and IDO1 amplification. This study marks the first demonstration of an HSV-2 derived OV's effectiveness against GBM. Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.

N-Desmethylmajusculamide B, a lipopeptide isolated from the Okinawan cyanobacterium Okeania hirsuta.

A new lipopeptide, N-desmethylmajusculamide B (1), was isolated from the Okinawan cyanobacterium Okeania hirsuta along with 2 known compounds majusculamide A (2) and majusculamide B (3). The planar structure of (1) was elucidated by a detailed analysis of mass spectrometry and nuclear magnetic resonance spectra. The absolute configurations of the amino acid residues were determined using Marfey's analysis. The configuration of C-16 in the α-methyl-ß-keto-decanoyl moiety was determined unambiguously to be S by conducting a semisynthesis of N-desmethylmajusculamide B from 3. The cytotoxicity against mouse L1210 leukemia cells was evaluated for majusculamides (1-3).

Methyl donor diet attenuates intimal hyperplasia after vascular injury in rats.

Environmental factors, particularly dietary habits, play an important role in cardiovascular disease susceptibility and progression through epigenetic modification. Previous studies have shown that hyperplastic vascular intima after endarterectomy is characterized by genome-wide hypomethylation. The purpose of this study was to investigate whether methyl donor diet affects intimal hyperplasia and the possible mechanisms involved. Intimal hyperplasia was induced in SD rats by carotid artery balloon injury. From 8 d before surgery to 28 d after surgery, the animals were fed a normal diet (ND) or a methyl donor diet (MD) supplemented with folic acid, vitamin B12, choline, betaine, and zinc. Carotid artery intimal hyperplasia was observed by histology, the effect of MD on carotid protein expression was analyzed by proteomics, functional clustering, signaling pathway, and upstream-downstream relationship of differentially expressed proteins were analyzed by bioinformatics. Results showed that MD attenuated balloon injury-induced intimal hyperplasia in rat carotid arteries. Proteomic analysis showed that there were many differentially expressed proteins in the common carotid arteries of rats fed with two different diets. The differentially expressed proteins are mainly related to the composition and function of the extracellular matrix (EMC), and changes in the EMC can lead to vascular remodeling by affecting fibrosis and stiffness of the blood vessel wall. Changes in the levels of vasculotropic proteins such as S100A9, ILF3, Serpinh1, Fbln5, LOX, HSPG2, and Fmod may be the reason why MD attenuates intimal hyperplasia. Supplementation with methyl donor nutrients may be a beneficial measure to prevent pathological vascular remodeling after injury.

Obesity and cancer: Mouse models used in studies.

There is increasing evidence that obesity is associated with the occurrence and development of malignant tumors. When studying the relationship between obesity and malignant tumors, it is very important to choose an appropriate animal model. However, BALB/c nude mice and other animals commonly used to study tumor xenograft (human-derived tumor cell lines) transplantation models are difficult to induce obesity, while C57BL/6 mice and other model animals commonly used for obesity research are not suitable for tumor xenograft transplantation. Therefore, it is difficult to replicate both obesity and malignancy in animal models at the same time. This review summarizes several experimental animal models and protocols that can simultaneously induce obesity and tumor xenografts.

Dietary B vitamins and glioma: A case-control study based on Chinese population.

Background: Dietary antioxidants have long been thought to be likely to prevent the development of gliomas. Previous studies have reported vitamin A, C, and E protective effects against gliomas. B vitamins, one of the main vitamins in the diet, are closely related to human health, but the association with gliomas has rarely been reported. Objective: This study aimed to evaluate the relationship between five B vitamins and glioma. Methods: In this Chinese population-based case-control study, 506 glioma cases and 506 matched (age and sex) controls were included. The dietary intake of study participants was assessed using a valid 111-item food frequency questionnaire. The intake of five B vitamins was calculated based on participants' dietary information from the food frequency questionnaire. The logistic regression model was used to examine the association between B vitamins and glioma, and the restriction cubic spline evaluated the dose-response relationship between the two. Results: After adjusting for confounding factors, thiamine (OR = 0.09, 95%CI: 0.05-0.20), riboflavin (OR = 0.12, 95%CI: 0.06-0.25), nicotinic acid (OR = 0.24, 95%CI: 0.12-0.47), folate (OR = 0.07, 95%CI: 0.03-0.15) and biotin (OR = 0.14, 95%CI: 0.07-0.30) in the highest tertile were associated with a significantly decreased risk of glioma compared with the lowest tertile. The results of thiamine and biotin in glioma with different pathological types and grades were different. The restricted cubic spline function showed significant dose-response relationships between the intake of five B vitamins and the risk of glioma. When B vitamins exceeded a specific intake, the risk of glioma did not change. Conclusion: Our study suggests that higher dietary intake of thiamine, riboflavin, nicotinic acid, and folate are associated with a decreased risk of glioma, but the results of biotin are not consistent among different populations. In the future, prospective studies should be conducted better to validate the effects of B vitamins on gliomas.

Osseous Metaplasia and Ectopic Bone Formation in a Patient With Hashimoto's Thyroiditis.

Thyroid nodules are frequently accompanied by degenerative changes, such as hemorrhage, cholesterol crystallization, fibrous tissue deposition, or filling with fat. Although calcification is also a common phenomenon, osteogenesis, characterized by mature bone formation, is very rare. Here, we describe a case of Hashimoto's thyroiditis with osseous metaplasia and ectopic bone formation case and discuss its possible causes.

Ectopic Thymic Carcinoma Located on The Dorsal Side of The Thyroid Gland.

Migration of the embryonic thymus is thought to be the basis for the formation of ectopic thymic tumors. Thymic ectopy may be a result of the abnormal migration of the third or fourth branchial cleft to the anterior mediastinum during weeks 5-6 of embryonic development. However, ectopic thymic carcinoma has highly nonspecific histologic features and occurs in variable and unpredictable locations making it difficult to diagnose. However, the clinical diagnosis and treatment should not overlook the possibility of ectopic thymic tumors. Here, we report a case of ectopic thymic carcinoma diagnosed as thyroid cancer before surgery occurring in a location consistent with current assumptions. Furthermore, we briefly review the literature on ectopic thymic carcinoma and discuss current diagnostic and treatment approaches.

Leptin receptor antagonist attenuates experimental autoimmune thyroiditis in mice by regulating Treg/Th17 cell differentiation.

Leptin has been found to be involved in the development and progression of many autoimmune diseases. As an organ-specific autoimmune disease, the pathogenesis of Hashimoto's thyroiditis has not been fully elucidated. It has been reported that serum leptin level is increased in Hashimoto's thyroiditis, but other studies have not shown any difference. We replicated a mouse model of experimental autoimmune thyroiditis (EAT) with a high-iodine diet and found that injection of the leptin receptor antagonist Allo-aca reduced thyroid follicle destruction and inflammatory cell infiltration in EAT mice, and thyroxine and thyroid autoimmune antibody levels. Further investigation revealed that Allo-aca promotes the differentiation of Treg cells and inhibits the differentiation of Th17 cells. We believe that Allo-aca can alter the differentiation of Treg/Th17 cells by inhibiting the leptin signaling pathway, thereby alleviating thyroid injury in EAT mice. Interfering with the leptin signaling pathway may be a novel new approach to treat treating and ameliorating Hashimoto's thyroiditis.

Decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells, TAMs and CAFsin tumor progression.

BACKGROUND: Single-cell transcription data provided unprecedented molecular information, enabling us to directly encode the ecosystem of colorectal cancer (CRC). Characterization of the diversity of epithelial cells and how they cooperate with tumor microenvironment cells (TME) to endow CRC with aggressive characteristics at single-cell resolution is critical for the understanding of tumor progression mechanism. METHODS: In this study, we comprehensively analyzed the single-cell transcription data, bulk-RNA sequencing data and pathological tissue data. In detail, cellular heterogeneity of TME and epithelial cells were analyzed by unsupervised classification and consensus nonnegative matrix factorization analysis, respectively. Functional status of epithelial clusters was annotated by CancerSEA and its crosstalk with TME cells was investigated using CellPhoneDB and correlation analysis. Findings from single-cell transcription data were further validated in bulk-RNA sequencing data and pathological tissue data. RESULTS: A distinct cellular composition was observed between tumor and normal tissues, and tumors exhibited immunosuppressive phenotypes. Regarding epithelial cells, we identified one highly invasiveQuery cluster, C4, that correlated closely with tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). Further analysis emphasized the TAMs subclass TAM1 and CAFs subclass S5 are closely related with C4. CONCLUSIONS: In summary, our study elaborates on the cellular heterogeneity of CRC, revealing that TAMs and CAFs were critical for crosstalk network epithelial cells and TME cells. This in-depth understanding of cancer cell-TME network provided theoretical basis for the development of new drugs targeting this sophisticated network in CRC.

Case report: The treatment for olfactory neuroblastoma combined with leptomeningeal carcinomatosis via an ommaya reservoir.

Olfactory neuroblastoma is a rare neoplasm that usually presents in the upper nasal cavity. Although its prognosis is highly unfavorable, effective treatment options are still lacking. Moreover, there is no standard treatment for patients with olfactory neuroblastoma that progressed to leptomeningeal carcinomatosis. Here we report an uncommon case of a 59-year-old woman who was diagnosed with olfactory neuroblastoma and leptomeningeal carcinomatosis. For a direct delivery of the drugs to the tumor, and to avoid the impact of lumbar puncture on the patient's quality of life, the intravenous chemotherapy plus intrathecal administration of MTX via an Ommaya reservoir was chosen. The results were striking, with the disappearance of tumor cells in the cerebrospinal fluid and the relief of the patient's symptoms with PR. Our result indicates that chemotherapy via an Ommaya reservoir offers a new potential therapy for patients with meningeal metastases.

Systematic Profiling of mRNA Splicing Reveals the Prognostic Predictor and Potential Therapeutic Target for Glioblastoma Multiforme.

Despite many changes in alternative splicing events (ASEs) are frequently involved in various cancers, prognosis-related ASEs and drug treatment targets in glioblastoma multiforme (GBM) have not been well explored. ASEs participate in many biological behaviors in the initiation and progression of tumors, the aberrant ASE has been considered another hallmark of cancer, and the systematic study of alternative splicing may provide potential biomarkers for malignancies. In this study, we carried out a systematic analysis to characterize the ASE signatures in GBM cohort. Through comparing GBM tissues and nontumor tissues, a total of 48,191 differently expressed ASEs from 10,727 genes were obtained, and these aberrant ASEs play an important role in the oncogenic process. Then, we identified 514 ASEs independently associated with patient survival in GBM by univariate and multivariate Cox regression, including exon skip in CD3D, alternate acceptor site in POLD2, and exon skip in DCN. Those prognostic models built on ASEs of each splice type can accurately predict the outcome of GBM patients, and values for the area under curve were 0.97 in the predictive model based on alternate acceptor site. In addition, the splicing-regulatory network revealed an interesting correlation between survival-associated splicing factors and prognostic ASE corresponding genes. Moreover, these three hub splicing factors in splicing regulation network are the potential targets of some drugs. In conclusion, a systematic analysis of ASE signatures in GBM could serve as an indicator for identifying novel prognostic biomarkers and guiding clinical treatment.

Identification of Prognostic Biomarkers for Multiple Solid Tumors Using a Human Villi Development Model.

The processes of embryonic development that rely on epithelial-mesenchymal transition (EMT) for the implantation of trophoblast cells are co-opted by tumors, reflecting their inherent uncontrolled characteristics and leading to invasion and metastasis. Although tumorigenesis and embryogenesis have similar EMT characteristics, trophoblasts have been shown to exhibit "physiological metastasis" or be "pseudo-malignant," resulting in different outcomes. The gene co-expression network is the basis of embryonic development and tumorigenesis. We hypothesize that if the gene co-expression network in tumors is "off-track" from that in villi, it is more likely to develop into malignant tumors and have a worse prognosis, and we proposed the "off-track theory" for the first time. In this study, we examined gene co-expression networks in villi and multiple solid tumors. Through network functional enrichment analyses, we found that most tumors and villi exhibited a significantly enriched EMT, but the genes that performed this function were not identical. Then, we identified the "off-track genes" in the EMT-related gene interaction network using the "off-track theory," and through survival analysis, we discovered that the risk score of "off-track genes" was associated with poor survival of cancer patients. Our study indicated that villi development is a reliable and strictly regulated model that can illuminate the trajectory of human cancer development and that the gene co-expression networks in tumor development are "off-track" from those in villi. These "off-track genes" may have a substantial impact on tumor development and could reveal novel prognostic biomarkers.

Distribution of microplastics in surface water of the lower Yellow River near estuary.

The composition and distribution of microplastics in surface water of the Yellow River lower reach near estuary were investigated in this work. The major shape types of microplastics can be classified to fibers, fragments and particles, and 93.12% of microplastics in the surface water were fibers. The microplastics <200 µm were most abundant at all sample sites, which accounted for 87.94% of microplastics. The composition of microplastics was identified as polyethylene, polypropylene, and polystyrene according to infrared spectrometer analysis. The amounts of primary microplastics accounted for approximately three-fourths according to scanning electron microscope and microscope photo observing. The microplastics at different weathering processes could be also observed. The average abundances of microplastics in the dry and wet seasons were 930 and 497 item/L, respectively. The abundances of microplastics in the dry season all higher than that in the wet season. The microplastic concentrations in the surface water decreased linearly with the distances from the estuary of Yellow River with rather high positive correlation coefficients at wet season (r = 0.8104, p < .01) and at dry season (r = 0.8333, p < .01). The distribution of microplastics in the river section and the density of microplastics may be the primary factors to influence the microplastic concentrations in the surface water. The researches about distribution of microplastics in the river section might provide useful information that could be used for calculating either mass fluxes or inventories of microplastics.

Characterization of Distinct T Cell Receptor Repertoires in Tumor and Distant Non-tumor Tissues from Lung Cancer Patients.

T cells and T cell receptors (TCRs) play pivotal roles in adaptive immune responses against tumors. The development of next-generation sequencing technologies has enabled the analysis of the TCRß repertoire usage. Given the scarce investigations on the TCR repertoire in lung cancer tissues, in this study, we analyzed TCRß repertoires in lung cancer tissues and the matched distant non-tumor lung tissues (normal lung tissues) from 15 lung cancer patients. Based on our results, the general distribution of T cell clones was similar between cancer tissues and normal lung tissues; however, the proportion of highly expanded clones was significantly higher in normal lung tissues than in cancer tissues (0.021% ±â€¯0.002% vs. 0.016% ±â€¯0.001%, P = 0.0054, Wilcoxon signed rank test). In addition, a significantly higher TCR diversity was observed in cancer tissues than in normal lung tissues (431.37 ±â€¯305.96 vs. 166.20 ±â€¯101.58, P = 0.0075, Mann-Whitney U test). Moreover, younger patients had a significantly higher TCR diversity than older patients (640.7 ±â€¯295.3 vs. 291.8 ±â€¯233.6, P = 0.036, Mann-Whitney U test), and the higher TCR diversity in tumors was significantly associated with worse cancer outcomes. Thus, we provided a comprehensive comparison of the TCR repertoires between cancer tissues and matched normal lung tissues and demonstrated the presence of distinct T cell immune microenvironments in lung cancer patients.

Immune microenvironments differ in immune characteristics and outcome of glioblastoma multiforme.

Understanding the interactions between tumors and the host immune system holds great promise to uncover biomarkers for targeted therapies, predict the prognosis of patients and guide clinical treatment. However, the immune signatures of glioblastoma multiforme (GBM) remain largely unstudied in terms of systematic analyses. We aimed to classify GBM samples according to immune-related genes and complement the existing immunotherapy system knowledge. In this study, we designed a strategy to identify 3 immune subtypes representing 3 different immune microenvironments (M1-M3) and associated with prognosis. The 3 subtypes were significantly different in terms of specific immune characteristics (immune cell subpopulations, immune responses, immune cells, and checkpoint gene interactions). In additional, copy number variations and methylation changes were identified that correlated with genes related to a worse prognosis subtype in the microenvironment. More importantly, in M3 (worst prognosis subtype) and M2 (best prognosis subtype), the interaction between immune cells and checkpoint genes was different, which had an important effect on the prognosis. Finally, we used risk scores of immune cells and checkpoint genes to evaluate the prognosis of GBM patients and validated the results with 3 independent datasets. Disordered interactions between immune cells and checkpoint genes result in a change in the immune microenvironment and affects the prognosis of patients. We propose that a better understanding of the immune microenvironment of advanced cancers may provide new insights into immunotherapy.

Identification of Distinct Immune Subtypes in Colorectal Cancer Based on the Stromal Compartment.

The tumor environment is of vital importance for the incidence and development of colorectal cancer. Increasing evidence in recent years has elaborated the vital role of the tumor environment in cancer subtype classification and patient prognosis, but a comprehensive understanding of the colorectal tumor environment that is purely dependent on the stromal compartment is lacking. To decipher the tumor environment in colorectal cancer and explore the role of its immune context in cancer classification, we performed a gene expression microarray on the stromal compartment of colorectal cancer and adjacent normal tissues. Through the integrated analysis of our data with public gene expression microarray data of stromal and epithelial colorectal cancer tissues processed through laser capture microdissection, we identified four highly connected gene modules representing the biological features of four tissue compartments by applying a weighted gene coexpression network analysis algorithm and classified colorectal cancers into three immune subtypes by adopting a nearest template prediction algorithm. A systematic analysis of the four identified modules mainly reflected the close interplay between the biological changes of intrinsic and extrinsic characteristics at the initiation of colorectal cancer. Colorectal cancers were stratified into three immune subtypes based on gene templates identified from representative gene modules of the stromal compartment: active immune, active stroma, and mixed type. These immune subtypes differed by the immune cell infiltration pattern, expression of immune checkpoint inhibitors, mutation landscape, extent of mutation burden, extent of copy number burden, prognosis and chemotherapeutic sensitivity. Further analysis indicated that activation of the NF-kB signaling pathway was the major mechanism causing the no immune infiltration milieu in the active stroma subtype and that inhibitors of the NF-kB signaling pathway could be candidate drugs for treating patients with an active stroma. Overall, these results suggest that characterizing colorectal cancer by the tumor environment is of vital importance in predicting patients' clinical outcomes and helping guide precision and personalized treatment.

Adsorption-associated orientational changes of immunoglobulin G and regulated phagocytosis of Staphylococcus epidermidis.

Understanding the adsorption of immunoglobulin G (IgG) on biomaterials surfaces is crucial for design and modification of the surfaces to alleviate inflammatory responses after implantation. Here, we report direct visualization and two-dimensional (2D) image interpretation of the IgG molecule adsorbed on simplified surfaces by single particle electron microscopy and atomic force microscopy. Influence of the orientational changes in adsorbed IgG on phagocytosis of macrophages against Staphylococcus epidermidis is further examined. Untreated amorphous carbon film and -COOH and -NH2 grafted carbon films are employed as the model surfaces for the adsorption testing. Results show that IgG displays flat orientation lying on the untreated surface, while forms vertical orientations standing on the functionalized surfaces. These specific spatial alignments are associated with altered unfolding extent and structure rearrangement of IgG domains, which are influenced synergistically by surface charge and wettability of the substrata. The changes in interdomain distance of IgG molecules subsequently regulate immune behaviors of macrophages and phagocytosis of S. epidermidis. The results would give insight into appropriate design of biomaterial surfaces in nanoscales for desired inflammatory responses. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2838-2849, 2018.