Mediator subunit MED8 interacts with heat shock transcription factor HSF3 to promote fucoxanthin synthesis in the diatom Phaeodactylum tricornutum.

Fucoxanthin, a natural carotenoid that has substantial pharmaceutical value due to its anticancer, antioxidant, antiobesity, and antidiabetic properties, is biosynthesized from glyceraldehyde-3-phosphate (G3P) via a series of enzymatic reactions. However, our understanding of the transcriptional mechanisms involved in fucoxanthin biosynthesis remains limited. Using reverse genetics, the med8 mutant was identified based on its phenotype of reduced fucoxanthin content, and the biological functions of MED8 in fucoxanthin synthesis were characterized using approaches such as gene expression, protein subcellular localization, protein-protein interaction and chromatin immunoprecipitation assay. Gene-editing mutants of MED8 exhibited decreased fucoxanthin content as well as reduced expression levels of six key genes involved in fucoxanthin synthesis, namely DXS, PSY1, ZDS-like, CRTISO5, ZEP1, and ZEP3, when compared to the wild-type (WT) strain. Furthermore, we showed that MED8 interacts with HSF3, and genetic analysis revealed their shared involvement in the genetic pathway governing fucoxanthin synthesis. Additionally, HSF3 was required for MED8 association with the promoters of the six fucoxanthin synthesis genes. In conclusion, MED8 and HSF3 are involved in fucoxanthin synthesis by modulating the expression of the fucoxanthin synthesis genes. Our results increase the understanding of the molecular regulation mechanisms underlying fucoxanthin synthesis in the diatom P. tricornutum.

Human serous cavity macrophages and dendritic cells possess counterparts in the mouse with a distinct distribution between species.

In mouse peritoneal and other serous cavities, the transcription factor GATA6 drives the identity of the major cavity resident population of macrophages, with a smaller subset of cavity-resident macrophages dependent on the transcription factor IRF4. Here we showed that GATA6+ macrophages in the human peritoneum were rare, regardless of age. Instead, more human peritoneal macrophages aligned with mouse CD206+ LYVE1+ cavity macrophages that represent a differentiation stage just preceding expression of GATA6. A low abundance of CD206+ macrophages was retained in C57BL/6J mice fed a high-fat diet and in wild-captured mice, suggesting that differences between serous cavity-resident macrophages in humans and mice were not environmental. IRF4-dependent mouse serous cavity macrophages aligned closely with human CD1c+CD14+CD64+ peritoneal cells, which, in turn, resembled human peritoneal CD1c+CD14-CD64- cDC2. Thus, major populations of serous cavity-resident mononuclear phagocytes in humans and mice shared common features, but the proportions of different macrophage differentiation stages greatly differ between the two species, and dendritic cell (DC2)-like cells were especially prominent in humans.

Modified bar bending method of thoracoscopic nuss procedure on pectus excavatum: a retrospective single-center study.

BACKGROUND: Pectus excavatum (PE) is the most common disease of chest wall deformity, with an incidence of 1 in 300-400 births. Nuss procedure has proved to be the best surgical treatment method and has been widely used after clinical use for 30 years. We aimed to review the clinical data of pectus excavatum (PE) of thoracoscopic Nuss procedure adopted the Modified bar bending method of the six-point seven-section type, and compare it with the traditional curved bar bending method to explore the clinical application effect. METHODS: Forty-six cases of clinical data were summarized of children with PE who adopted the treatment of the Modified bar bending method of the six-point seven-section type from January 2019 to December 2021, and 51 cases were compared of PE children who adopted the treatment of traditional curved bar bending method from January 2016 to December 2018, including the data of age, gender, preoperative symptoms, symmetry, Haller index, operation time, bar bending time, intraoperative bleeding, postoperative complications, bar migration, postoperative effect evaluation, etc. RESULTS: The Procedure duration (P = 0.008), bar bending time (P < 0.001), and duration of postoperative pain (P < 0.001) were reduced significantly, and the incidence of bar migration after surgery was reduced as well by the modified bar bending method. There was no difference compared with traditional Nuss produce, like the incidence of evaluation of postoperative effects (Excellent, P = 0.93; Good, P = 0.80; Medium, P = 1.00; Poor, P = 1.00), bar migration (P = 1.00), postoperative complications (P = 1.00), Clavien- Dindo classification of surgical complications (I = 0.165; II = 1.00; IIIa = 1.00; IIIb = 1.00; VI = 1.00; V = 1.00), operative safety, and operative validity. CONCLUSION: Modified bar bending method of the six-point seven-section type, which is a kind of surgical method worth applying and popularizing, and the advantages of minimally procedure duration, bar bending time, and duration of postoperative pain, compared with the traditional bar bending method.

Effect of high glucose supplementation on pulmonary fibrosis involving reactive oxygen species and TGF-ß.

This study explored the profibrotic impact of high glucose in the lung and potential mechanisms using latent TGF-ß1-induced human epithelial cell pulmonary fibrosis and bleomycin (BLM)-induced pulmonary fibrosis models. Results demonstrated that high glucose administration induced epithelial-mesenchymal transition (EMT) in human epithelial cells in a dose-dependent manner via activating latent TGF-ß1, followed by increased expression of mesenchymal-related proteins and decreased expression of epithelial marker protein E-cadherin. Further mechanism analysis showed that administration of high glucose dose-dependently promoted total and mitochondrial reactive oxygen species (ROS) accumulation in human epithelial cells, which promoted latent TGF-ß1 activation. However, N-acetyl-L-cysteine, a ROS eliminator, inhibited such effects. An in vivo feed study found that mice given a high-glucose diet had more seriously pathological characteristics of pulmonary fibrosis in BLM-treated mice, including increasing infiltrated inflammatory cells, collagen I deposition, and the expression of mesenchymal-related proteins while decreasing the expression of the epithelial marker E-cadherin. In addition, high glucose intake further increased TGF-ß1 concentration and upregulated p-Smad2/3 and snail in lung tissues from BLM-treated mice when compared to BLM-treated mice. Finally, supplementation with high glucose further increased the production of lipid peroxidation metabolite malondialdehyde and decreased superoxide dismutase activity in BLM-treated mice. Collectively, these findings illustrate that high glucose supplementation activates a form of latent TGF-ß1 by promoting ROS accumulation and ultimately exacerbates the development of pulmonary fibrosis.

Pentagalloylglucose disrupts the PALB2-BRCA2 interaction and potentiates tumor sensitivity to PARP inhibitor and radiotherapy.

DNA damage repair plays a vital role in maintaining the genomic integrity of cells and has been exploited therapeutically in the treatment of cancer. We have previously demonstrated that the upregulation of CXorf67 in posterior fossa type A ependymoma sensitizes tumor cells to PARP inhibitors by suppressing the PALB2-BRCA2 protein-protein interaction (PPI). Here, we performed structure-based virtual screening of ∼2 million small molecular entities followed by NanoBiT-based screening, and determined that pentagalloylglucose (PGG) disrupts the PALB2-BRCA2 PPI. Structure-based molecular docking and in vitro binding affinity assays revealed that PGG occupies a well-defined binding groove in the tips of the fourth and fifth blades of the PALB2 WD40 domain. PGG reduces BRCA2 recruitment to DNA damage sites and inhibits the formation of RAD51 foci, suppressing homologous recombination repair. PGG also inhibits proliferation and survival in several cancer cell lines, including breast cancer and medulloblastoma cells, and suppresses the in vivo growth of tumor xenografts. Thus, PGG is a specific inhibitor of the PALB2-BRCA2 PPI, which has potential value in cancer treatment to sensitize tumors to PARP inhibitors and radiotherapy.

Fructose Induces Pulmonary Fibrotic Phenotype Through Promoting Epithelial-Mesenchymal Transition Mediated by ROS-Activated Latent TGF-ß1.

Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-ß1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-ß1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-ß type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-ß1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-ß1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-ß1 into activated TGF-ß1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.

Resident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma.

The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8+ T cells were defined by the tissue of occupancy. Parabiosis revealed that tumor-specific Trm and Tcirm compartments persisted throughout visceral organs, but Trm cells dominated lymph nodes (LNs). Single-cell RNA-sequencing profiles of Trm cells in LN and skin were distinct, and T cell clonotypes that occupied both tissues were overwhelmingly maintained as Trm in LNs. Whereas Tcirm cells prevented melanoma growth in the lungs, Trm afforded long-lived protection against melanoma seeding in LNs. Expanded Trm populations were also present in melanoma-involved LNs from patients, and their transcriptional signature predicted better survival. Thus, tumor-specific Trm cells persist in LNs, restricting metastatic cancer.

Resident and circulating memory T cells persist for years in melanoma patients with durable responses to immunotherapy.

While T-cell responses to cancer immunotherapy have been avidly studied, long-lived memory has been poorly characterized. In a cohort of metastatic melanoma survivors with exceptional responses to immunotherapy, we probed memory CD8+ T-cell responses across tissues, and across several years. Single-cell RNA sequencing revealed three subsets of resident memory T (TRM) cells shared between tumors and distant vitiligo-affected skin. Paired T-cell receptor sequencing further identified clonotypes in tumors that co-existed as TRM in skin and as effector memory T (TEM) cells in blood. Clonotypes that dispersed throughout tumor, skin, and blood preferentially expressed a IFNG / TNF-high signature, which had a strong prognostic value for melanoma patients. Remarkably, clonotypes from tumors were found in patient skin and blood up to nine years later, with skin maintaining the most focused tumor-associated clonal repertoire. These studies reveal that cancer survivors can maintain durable memory as functional, broadly-distributed TRM and TEM compartments.

Large intraperitoneal lipoleiomyoma in a pre-menopausal woman: a case report.

BACKGROUND: Lipoleiomyoma is a rare, benign variant of the commonplace uterine leiomyoma. Unlike leiomyoma, these tumors are composed of smooth muscle cells admixed with mature adipose tissue. While rare, they are most frequently identified in the uterus, but even more infrequently have been described in extrauterine locations. CASE PRESENTATION: We describe a case report of a 45-year-old woman with a history of in vitro fertilization pregnancy presenting 6 years later with abdominal distention and weight loss found to have a 30-cm intra-abdominal lipoleiomyoma. While cross-sectional imaging can narrow the differential diagnosis, histopathological analysis with stains positive for smooth muscle actin, desmin, and estrogen receptor, but negative for HMB-45 confirms the diagnosis of lipoleiomyoma. The large encapsulated tumor was resected en bloc. The patients post-operative course was uneventful and her symptoms resolved. CONCLUSIONS: Lipoleiomyoma should be considered on the differential diagnosis in a woman with a large intra-abdominal mass. While considered benign, resection should be considered if the mass is symptomatic, and the diagnosis is unclear or there is a concern for malignancy.

Memory CD8+ T cell responses to cancer.

Long-lived memory CD8+ T cells play important roles in tumor immunity. Studies over the past two decades have identified four subsets of memory CD8+ T cells - central, effector, stem-like, and tissue resident memory - that either circulate through blood, lymphoid and peripheral organs, or reside in tissues where cancers develop. In this article, we will review studies from both pre-clinical mouse models and human patients to summarize the phenotype, distribution and unique features of each memory subset, and highlight specific roles of each subset in anti-tumor immunity. Moreover, we will discuss how stem-cell like and resident memory CD8+ T cell subsets relate to exhausted tumor-infiltrating lymphocytes (TIL) populations. These studies reveal how memory CD8+ T cell subsets together orchestrate durable immunity to cancer.

Elevated CXorf67 Expression in PFA Ependymomas Suppresses DNA Repair and Sensitizes to PARP Inhibitors.

Ependymoma is the third most common pediatric tumor with posterior fossa group A (PFA) being its most aggressive subtype. Ependymomas are generally refractory to chemotherapies and thus lack any effective treatment. Here, we report that elevated expression of CXorf67 (chromosome X open reading frame 67), which frequently occurs in PFA ependymomas, suppresses homologous recombination (HR)-mediated DNA repair. Mechanistically, CXorf67 interacts with PALB2 and inhibits PALB2-BRCA2 interaction, thereby inhibiting HR repair. Concordantly, tumor cells with high CXorf67 expression levels show increased sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with radiotherapy. Thus, our findings have revealed a role of CXorf67 in HR repair and suggest that combination of PARP inhibitors with radiotherapy could be an effective treatment option for PFA ependymomas.

Effects of row direction and row spacing on maize leaf senescence.

To analyze three row orientations (south-north, east-west, southwestern 20°) and two row spacings ('65 + 65', '160 + 40'), we investigated the effect of row orientation and planting pattern on photosynthetic performance, physiological and biochemical indicators related to the aging of leaves. Results revealed that during maturity stage, in north-south and east-west, the initial fluorescence (Fo) at '65 + 65' were higher than those under'160 + 40'; the maximum quantum yield of PS2 photochemistry(ΦP0), basal quantum yield of non-photochemical processes in PS2(ΦN0)of the lower leaves and photosynthetic rate of the upper and ear leaves under'160 + 40'were higher than those under'65 + 65'. The polyphenoloxidase (POD) activities of leaves at different positions under '160 + 40' were higher than that under'65 + 65', while the malondialdehyde (MDA) content was lower. The photosynthesis rate, superoxide dismutase (SOD) and catalase (CAT) activity of leaves at different positions under southwestern 20° '160 + 40' were higher than others. Whilst MDA content '160 + 40' were lower. Therefore, in De Hui City, Jilin Province, southwestern 20° '160 + 40' delayed leaf senescence at the late stage of growth of maize, as well as the effect of increasing maize yield was most obvious.

Human health risk assessment of groundwater arsenic contamination in Jinghui irrigation district, China.

The groundwater is an important route of human exposure to kinds of contaminants. This study was carried out to investigate the occurrence and spatial distribution of groundwater arsenic in the Jinghui irrigation district in Shaanxi Province, China. The water contamination was assessed for drinking purposes by comparing it to national guidelines, and the impacts of arsenic on human health were quantified using the health risk assessment model recommended by the USEPA. The results show that the concentration of groundwater arsenic ranges from 0.0012 to 0.0190 mg/L (average 0.0054 mg/L), and 2.58% of groundwater exceed the national guidelines of 0.01 mg/L for drinking. The carcinogenic risk of arsenic affecting adults has reached 3.50 × 10-4, significantly exceeding the national guideline (1.00 × 10-4.) The health risks resulting from oral exposure are higher than those of dermal exposure. The carcinogenic risk for adults is higher than that for children, while the non-carcinogenic risk for children is higher than that for adults. The area ratio of the carcinogenic risk is 42.82%, and the area of the non-carcinogenic risk is 69.19%. Groundwater arsenic mainly originates from the discharge of industrial wastewater and the slowly release of natural sediments. The results of this study can help to set up suitable management strategies to guarantee water supply and health safety for local residents.

Large-Scale Cultivation of Spirulina for Biological CO2 Mitigation in Open Raceway Ponds Using Purified CO2 From a Coal Chemical Flue Gas.

In order to select excellent strains with high CO2 fixation capability on a large scale, nine Spirulina species were cultivated in columnar photobioreactors with the addition of 10% CO2. The two species selected (208 and 220) were optimized for pH value, total dissolved inorganic carbon (DIC), and phosphorus content with intermittent CO2 addition in 4 m2 indoor raceway ponds. On the basis of biomass accumulation and CO2 fixation rate in the present study, the optimum pH, DIC, and phosphate concentration were 9.5, 0.1 mol L-1, and 200 mg L-1 for both strains, respectively. Lastly, the two strains selected were semi-continuously cultivated successfully for CO2 mitigation in 605 m2 raceway ponds aerated with food-grade CO2 purified from a coal chemical flue gas on a large scale. The daily average biomass dry weight of the two stains reached up to 18.7 and 13.2 g m-2 d-1, respectively, suggesting the two Spirulina strains can be utilized for mass production.

Promoter methylations of RASSF1A and p16 is associated with clinicopathological features in lung cancers.

UNLABELLED: Objection: The aim of this study is to investigate the association between promoter methylation of RASSF1A and p16 and the clinicopathological features in lung cancers. MATERIALS AND METHODS: PubMed, EBSCO, Ovid, Wiley, Web of Science, Wanfang, and VIP databases were searched using combinations of keywords related to RASSF1A, p16, methylation, and lung cancers. After screening for relevant studies, following a strict inclusion and exclusion criteria; the selected studies were incorporated into the present meta.analysis conducted using Comprehensive Meta Analysis 2.0. (CMA 2.0). RESULTS: We initially retrieved 402 studies, out which 13 studies met the inclusion and exclusion criteria for this meta.analysis, and contained a total of 1,259. patients with lung cancers. The results of this meta.analysis showed that the differences in promoter methylation ratio between the lung cancer patients in tumor, node, metastasis. (TNM) I.II and III.IV were not statistically significant. Based on histological types, patients with adenocarcinoma. (AC) and squamous cell carcinoma. (SCC) showed no significant differences in the promoter methylation ratios of RASSF1A, while the promoter methylation ratio of p16 was significantly higher in SCC patients compared to AC patients. Based on smoking status, the promoter methylation ratios of both RASSF1A and p16 was significantly higher in lung cancer patients with smoking history compared to nonsmokers. CONCLUSION: The present meta.analysis provides convincing evidence that the promoter methylation ratio of RASSF1A and p16 is associated with clinicopathological features in lung cancers, and could be used as effective biomarkers in early diagnosis in lung cancers.

miR-206 inhibits non small cell lung cancer cell proliferation and invasion by targeting SOX9.

BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been suggested to play an essential role in tumorigenesis. miR-206 functions as a tumor suppressor in several cancers. However, its role in non small cell lung cancer (NSCLC) remains unclear. METHODS: Expression levels of miR-206 in NSCLC tissues and cell lines were determined by quantitative real-time PCR (qRT-PCR). Then, we investigated the role of miR-206 on NSCLC cell proliferation, migration and invasion. Furthermore, luciferase reporter assay was performed to confirm the target gene of miR-206 and the results were validated in NSCLC cells. RESULTS: In the present study, our results showed that miR-206 was decreased in NSCLC tissues compared with adjacent non-tumor tissues. Forced overexpression of miR-206 significantly inhibited cell proliferation, migration and invasion of NSCLC cells. SOX9 was found to be a target of miR-206. Furthermore, down-regulation of SOX9 by shRNA performed similar effects with overexpression of miR-206. CONCLUSIONS: Our study suggested that miR-206 acts as tumor suppressor in NSCLC partially via targeting SOX9.

StIL-17 gene polymorphisms in the development of pulmonary tuberculosis.

UNLABELLED: We conduct a case-control study to explore the possible association between IL-17 gene polymorphisms and development of TB. METHODS: The study population comprised 428 TB subjects and 428 control subjects between January 2013 and June 2014. Genotyping analyses of IL-17A rs2275913 and rs3748067 and IL-17F rs763780 and rs9382084 were analyzed using polymerase chain reaction-restriction fragment length of polymorphism (PCR-RFLP). RESULTS: The TB cases were more likely to have a habit of smoking when comparing with controls. By conditional logistic regression analysis, individuals carrying CC genotype of rs763780 were more likely to have a significantly increased risk of TB when compared with TT genotype. The OR (95% CI) for CC genotype of rs763780 was 2.98 (1.58-5.92). CONCLUSION: In conclusion, we suggest that rs763780 play a critical role in the etiology of TB. These findings could be helpful in identifying individuals at increased risk for developing TB.

Down-regulation of microRNA-124 is correlated with tumor metastasis and poor prognosis in patients with lung cancer.

INTRODUCTION: MicroRNA-124 (miR-124) has been proven dysregulated in several human malignancies and correlated with tumor progression. However, its expression and clinical significance in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to investigate the clinical significance of miR-124 expression in NSCLC. METHODS: Expression levels of miR-124 in 92 pairs of NSCLC and adjacent non-tumor tissues were detected by quantitative real-time PCR (qRT-PCR). In order to determine its prognostic value, overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. RESULTS: miR-124 expression level was significantly lower in NSCLC tissues compared with adjacent non-tumor tissues (P < 0.05). The 5-year OS of low miR-124 expression group was significantly shorter than that of high miR-124 expression group (P < 0.05). Moreover, the 5-year DFS of low miR-124 expression group was also significantly shorter than that of high miR-124 expression group (P < 0.05). In a multivariate Cox model, we found that miR-124 expression was an independent prognostic factor for both 5-year OS and 5-year DFS in NSCLC (P < 0.05). CONCLUSIONS: Our results offer the convincing evidence that miR-124 may play key roles in the progression of lung cancer and that the down-regulated expression of miR-124 may be independently associated with shorter OS and DFS of patients, suggesting that miR-124 might be a potential marker for further risk stratification in the treatment of lung cancer.

Associations of LIG4 and HSPB1 genetic polymorphisms with risk of radiation-induced lung injury in lung cancer patients treated with radiotherapy.

OBJECTIVE: This study aims to explore the correlations of genetic polymorphisms in LIG4 and HSPB1 genes with the radiation-induced lung injury (RILI), especially radiation pneumonitis (RP), in lung cancer patients. METHODS: A total of 160 lung cancer patients, who were diagnosed with inoperable lung cancer and received radiotherapy, were included in the present study from September 2009 to December 2011. TaqMan Real-Time PCR (RT-PCR) was used to verify the SNPs of LIG4 and HSPB1 genes. Chi-square criterion was used to compare the differences in demographic characteristics, exposure to risk factors, and SNPs genotypes. Crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated by logistic regression analysis. All statistical analyses were conducted in SPSS 18.0. RESULTS: A total of 32 (20.0%) lung cancer patients had RP after receiving radiotherapy. Of the 32 cases, 4 cases were of grade 2, 24 cases were of grade 3, and 4 cases were of grade 4. However, our results indicated that the general condition and treatment of all patients had no significant difference with RP risk (P > 0.05). Meanwhile, our results revealed that there was no significant association between the frequencies of LIG4 rs1805388 and HSPB1 rs2868371 genotype distribution and the risk of RP (P > 0.05). CONCLUSION: In conclusion, we demonstrated that the genetic polymorphisms in LIG4 rs1805388 and HSPB1 rs2868371 were not obviously correlated with the risk of RP and RILI of lung cancer.