GDF9His209GlnfsTer6/S428T and GDF9Q321X/S428T bi-allelic variants caused female subfertility with defective follicle enlargement.

BACKGROUND: Antral follicles consist of an oocyte cumulus complex surrounding by somatic cells, including mural granulosa cells as the inner layer and theca cells as the outsider layer. The communications between oocytes and granulosa cells have been extensively explored in in vitro studies, however, the role of oocyte-derived factor GDF9 on in vivo antral follicle development remains elusive due to lack of an appropriate animal model. Clinically, the phenotype of GDF9 variants needs to be determined. METHODS: Whole-exome sequencing (WES) was performed on two unrelated infertile women characterized by an early rise of estradiol level and defect in follicle enlargement. Besides, WES data on 1,039 women undergoing ART treatment were collected. A Gdf9Q308X/S415T mouse model was generated based on the variant found in one of the patients. RESULTS: Two probands with bi-allelic GDF9 variants (GDF9His209GlnfsTer6/S428T, GDF9Q321X/S428T) and eight GDF9S428T heterozygotes with normal ovarian response were identified. In vitro experiments confirmed that these variants caused reduction of GDF9 secretion, and/or alleviation in BMP15 binding. Gdf9Q308X/S415T mouse model was constructed, which recapitulated the phenotypes in probands with abnormal estrogen secretion and defected follicle enlargement. Further experiments in mouse model showed an earlier expression of STAR in small antral follicles and decreased proliferative capacity in large antral follicles. In addition, RNA sequencing of granulosa cells revealed the transcriptomic profiles related to defective follicle enlargement in the Gdf9Q308X/S415T group. One of the downregulated genes, P4HA2 (a collagen related gene), was found to be stimulated by GDF9 protein, which partly explained the phenotype of defective follicle enlargement. CONCLUSIONS: GDF9 bi-allelic variants contributed to the defect in antral follicle development. Oocyte itself participated in the regulation of follicle development through GDF9 paracrine effect, highlighting the essential role of oocyte-derived factors on ovarian response.

Effective degradation of polystyrene microplastics by Ti/La/Co-Sb-SnO2 anodes: Enhanced electrocatalytic stability and electrode lifespan.

Microplastics have been identified as an emerging pollutant that poses a risk to the aquatic environment, and it is a challenge to find a suitable removal process. Electrocatalytic oxidation (ECO) technology has shown promising performance in removing various persistent organic pollutants. In this study, we prepared a new anode for removing polystyrene microplastics (PS MPs) by ECO. Ti/La-Sb-SnO2 electrodes doped with the rare earth element La as the active layer were synthesized to enhance the electrocatalytic activity. The lifespan of the electrode was improved by doping Mn, Co, or Ru as an intermediate layer modification between the titanium (Ti) substrate and the La-Sb-SnO2 active layer, respectively. The experimental results indicated that the addition of three types of intermediate layers led to different degrees of decrease in the catalytic activity of the electrode and the degradation performance of PS MPs. The addition of the Co intermediate layer had a negligible effect on the catalytic activity and performance of the Ti/La-Sb-SnO2 anode for PS degradation. In addition, the electrode lifespan with Co intermediate layer was significantly prolonged, which was 4.54, 2.38, and 1.19 times higher than the electrode without intermediate layer and the electrode with Ru and Mn intermediate layer, respectively. Therefore, Co was determined to be the optimal choice as the intermediate layer, and the production technique for the Ti/La/Co-Sb-SnO2 anodes was carefully adjusted. The degradation efficiency of PS MPs was optimized at a heat treatment temperature of 400 °C and a Sn: Co material ratio of 5:1, with a removal rate of 28.0 %. The ECO treatment also resulted in more pronounced changes in the structure and functional groups of the MPs. Various alkyl cleavage and oxidation products were detected after the treatment, suggesting that the oxidant (hydroxyl radicals) strongly interacted with the MPs, leading to their degradation. Overall, this work provided a new insight into removing MPs in water through the use of modified electrodes.

The Screening and Identification of a Dextranase-Secreting Marine Actinmycete Saccharomonospora sp. K1 and Study of Its Enzymatic Characteristics.

In this study, an actinomycete was isolated from sea mud. The strain K1 was identified as Saccharomonospora sp. by 16S rDNA. The optimal enzyme production temperature, initial pH, time, and concentration of the inducer of this actinomycete strain K1 were 37 °C, pH 8.5, 72 h, and 2% dextran T20 of medium, respectively. Dextranase from strain K1 exhibited maximum activity at 8.5 pH and 50 °C. The molecular weight of the enzyme was <10 kDa. The metal ions Sr2+ and K+ enhanced its activity, whereas Fe3+ and Co2+ had an opposite effect. In addition, high-performance liquid chromatography showed that dextran was mainly hydrolyzed to isomaltoheptose and isomaltopentaose. Also, it could effectively remove biofilms of Streptococcus mutans. Furthermore, it could be used to prepare porous sweet potato starch. This is the first time a dextranase-producing actinomycete strain was screened from marine samples.

Dextranase Production Using Marine Microbacterium sp. XD05 and Its Application.

Dextranase, also known as glucanase, is a hydrolase enzyme that cleaves α-1,6 glycosidic bonds. In this study, a dextranase-producing strain was isolated from water samples of the Qingdao Sea and identified as Microbacterium sp. This strain was further evaluated for growth conditions, enzyme-producing conditions, enzymatic properties, and hydrolysates. Yeast extract and sodium chloride were found to be the most suitable carbon and nitrogen sources for strain growth, while sucrose and ammonium sodium were found to be suitable carbon and nitrogen sources for fermentation. The optimal pH was 7.5, with a culture temperature of 40 °C and a culture time of 48 h. Dextranase produced by strain XD05 showed good thermal stability at 40 °C by retaining more than 70% relative enzyme activity. The pH stability of the enzyme was better under a weak alkaline condition (pH 6.0-8.0). The addition of NH4+ increased dextranase activity, while Co2+ and Mn2+ had slight inhibitory effects on dextranase activity. In addition, high-performance liquid chromatography showed that dextran is mainly hydrolyzed to maltoheptanose, maltohexanose, maltopentose, and maltootriose. Moreover, it can form corn porous starch. Dextranase can be used in various fields, such as food, medicine, chemical industry, cosmetics, and agriculture.

Examining Financial Risk Contagion and Shock Response via Complex Network Analysis of Correlation and Causality in the Sports Industry / Examinar el contagio del riesgo financiero y la respuesta al shock a través de un análisis de red complejo de correlación y causalidad en la industria del deporte

In today's landscape of financial liberalization and economic integration, the sports industry is not immune to the complex interplay between financial and economic activities. This dynamic environment witnesses the frequent exchange of information within the sports financial market, resulting in a high degree of interaction. Such interaction has not only optimized the allocation of global financial resources in sports but has also amplified the repercussions and dissemination of financial crises within the sports sector. From the global sports financial system to individual sports entities, intricate relationships emerge in economic and financial activities among countries, forming a complex sports financial ecosystem. Understanding and characterizing the patterns of risk propagation and shock responses in the sports financial market is vital. It equips sports market participants and regulators with crucial market insights, aids in policy formulation, and enables proactive measures to prevent and address financial market crises within the sports industry. Considering the multifaceted interactions among various stakeholders in the sports financial market, this study adopts a complex network methodology to examine the dynamics of financial risk contagion and shock response, with a primary focus on the sports industry. This approach offers a valuable perspective, shedding light on the specific intricacies within the sports finance domain.(AU)

Combined Application Effects of Arbuscular Mycorrhizal Fungi and Biochar on the Rhizosphere Fungal Community of Allium fistulosum L.

Arbuscular mycorrhizal fungi (AMF) are widespread soil endophytic fungi, forming mutualistic relationships with the vast majority of land plants. Biochar (BC) has been reported to improve soil fertility and promote plant growth. However, limited studies are available concerning the combined effects of AMF and BC on soil community structure and plant growth. In this work, a pot experiment was designed to investigate the effects of AMF and BC on the rhizosphere microbial community of Allium fistulosum L. Using Illumina high-throughput sequencing, we showed that inoculation of AMF and BC had a significant impact on soil microbial community composition, diversity, and versatility. Increases were observed in both plant growth (the plant height by 8.6%, shoot fresh weight by 12.1%) and root morphological traits (average diameter by 20.5%). The phylogenetic tree also showed differences in the fungal community composition in A. fistulosum. In addition, Linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed that 16 biomarkers were detected in the control (CK) and AMF treatment, while only 3 were detected in the AMF + BC treatment. Molecular ecological network analysis showed that the AMF + BC treatment group had a more complex network of fungal communities, as evidenced by higher average connectivity. The functional composition spectrum showed significant differences in the functional distribution of soil microbial communities among different fungal genera. The structural equation model (SEM) confirmed that AMF could improve the microbial multifunctionality by regulating the rhizosphere fungal diversity and soil properties. Our findings provide new information on the effects of AMF and biochar on plants and soil microbial communities.

Anti-inflammatory therapeutic biomarkers identified of human bone marrow mesenchymal stem cell therapy on aging mice by serum proteomics and peptidomics study.

Aging is accompanied by deterioration in physical condition, and creates high risks of diseases. Stem cell therapy exhibited promising potential in delaying aging. However, the unelucidated therapeutic mechanism limits future clinical application. Herein, to systematically understand the response to stem cell transfusion at the molecular level, we performed quantitative serum proteomic and peptidomics analyses in the 24-month-old aging mice model with or without mesenchymal stem cell (MSC) treatment. As a result, a total of 560 proteins and 2131 endogenous peptides were identified, among which, 6 proteins and 9 endogenous peptides derived from 6 precursor proteins were finally identified as therapeutic biomarkers after MSC transfusion on aging mice both by untargeted label-free quantification and targeted parallel reaction monitoring (PRM) quantification. Amazingly, the biological function of these differential proteins was mainly related to inflammation, which is not only the important hallmark of aging, but also the main cause of inducing aging. The reduction of these inflammatory protein content after MSC treatment further suggests the anti-inflammatory effect of MSC therapy reported elsewhere. Therefore, our study provides new evidence for the anti-inflammatory effect of MSC therapy for anti-aging and offers abundant data to support deeper investigations of the therapeutic mechanism of MSC in delaying aging.

LTF Induces Radioresistance by Promoting Autophagy and Forms an AMPK/SP2/NEAT1/miR-214-5p Feedback Loop in Lung Squamous Cell Carcinoma.

Radiotherapy is the most predominant treatment strategy for lung squamous cell carcinoma (LUSC) patients, but radioresistance is the major obstacle to therapy effectiveness. The mechanisms and regulators of LUSC radioresistance remain unclear. Here, lactotransferrin (LTF) is found to be significantly upregulated in radioresistant LUSC cell lines (H226R and H1703R) and clinical samples and promotes radioresistance of LUSC both in vitro and in vivo. Comprehensive enrichment analyses suggested that LTF potentially modulates autophagy in LUSC. Interestingly, the level of autophagy was raised in the radioresistant cells, and suppression of autophagy sensitized LUSC to irradiation. Functional experiments showed that LTF deficiency inhibits cellular autophagy through the AMPK pathway, ultimately leading to radiosensitization. Mechanistically, LTF can directly interact with AMPK to facilitate its phosphorylation and activate autophagy signaling. Moreover, NEAT1 functions as a ceRNA that targets miR-214-5p resulting in an increased LTF expression. Intriguingly, SP2, a transcription factor regulated by AMPK, induced NEAT1 expression by directly binding to its promoter region and thus forming a LTF/AMPK/SP2/NEAT1/miR-214-5p feedback loop. Our work reveals for the first time that LTF induces radioresistance by promoting autophagy and enhancing its self-expression via forming a positive feedback loop, suggesting that LTF is an appealing radiosensitization target for treating LUSC.

Epidemiological landscape of esophageal cancer in Asia: Results from GLOBOCAN 2020.

BACKGROUND: Esophageal cancer (EC) is a global health problem. Asia represents a huge burden of EC globally, and incidence and mortality vary considerably across different Asian regions. METHODS: Data on incidence, mortality, and preference were extracted from GLOBOCAN 2020. Age-standardized incidence and mortality rates were calculated overall by sex, age, country, region, and continent. The predicted burden of incidence and mortality in 2040 was calculated based on global demographic projections. RESULTS: It was estimated there were 481 552 new cases of and 434 363 deaths from EC in Asia in 2020, accounting for 79.7% and 79.8% of world EC cases and deaths, respectively. EC incidence and mortality in Asia ranked the highest among all continents. Eastern Asia represents the highest age-standardized world incidence rate (ASWIR) of 12.3 per 100 000 for all Asian regions. Western Asia represents the lowest ASWIR of 1.7 per 100 000, accounting for 0.7% of the globe. There exist obvious differences in epidemiological features in Asian countries, including incidence, mortality, prevalence, and mortality incidence ratio. There is forecast to be up to 781 000 new cases of EC in Asia by 2040, with increasing rates of 63% for incidence and 72% for mortality from 2020. CONCLUSIONS: Asia has an increasing number of EC cases and deaths. Strategies for targeting in high-incidence areas, the elderly, and survival should be prioritized to reduce the global EC burden, especially in low- and middle-income countries in Asia.

Preparation of Co/Cu-based bi-MOFs and the degradation of sulfamethoxazole by activated peracetic acid.

Compared with the common synthesis methods of metal-organic frameworks (MOFs), Co/Cu-based bi-MOFs composite catalyst CoXCu(10-X)-MOFs (X = 2, 4, 6, and 8) was prepared by a facile synthesis method at room temperature. The bi-MOFs composite catalyst was characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The removal ability of sulfamethoxazole (SMX) by different Co:Cu rate bi-MOFs composite catalysts, single Co-based MOFs (zeolitic imidazolate framework-67, ZIF-67), and Cu-based MOFs (Hong Kong University of Science and Technology-1, HKUST-1) were investigated and the effects of peracetic acid (PAA) concentration, catalyst dosage, the common interfering substances (Cl-, HCO3-, SO42-, HA) in water, and SMX removal were investigated. Through the analysis of different free radical scavengers and the changes of surface elements before and after the reaction, the oxidation mechanism was further explored, and the stability of Co4Cu6-MOFs was explored through repeated recycling. The experimental results demonstrate that Co4Cu6-MOFs have a high catalytic activity for PAA. Co4Cu6-MOFs/PAA show the best removal effect of SMX under neutral conditions and the presence of Cl- and HCO3- can promote the removal of SMX.

iPSCs-derived mesenchymal stromal cells mitigate anxiety and neuroinflammation in aging female mice.

Perimenopause is a natural transition to menopause, when hormone disturbance can result in both short-term mental disorders, such as anxiety, and long-term neuroinflammation due to blood-brain barrier (BBB) impairment, which may lead to more serious neurological disorders later on, such as dementia. Effective treatments may prevent both short-term and long-term neurological sequela, which formed the aim of this study. In aged female C57BL/6 mice (16-18 months of age), mesenchymal stromal cells (MSCs) differentiated from human-induced pluripotent stem cells (iPSCs), were administered via tail vein injection. Mice showed increased blood estrogen levels, alleviated anxiety and neuroinflammation, and improved BBB integrity. Interestingly, transplanted MSCs were located close to ovarian sympathetic nerves and decreased ovarian norepinephrine levels, which in turn increased ovarian estrogen secretion. Moreover, the administration of anastrozole, an inhibitor of estrogen synthesis, diminished the therapeutic effects of MSCs in vivo, suggesting the effect to be estrogen-dependent. In vitro study confirmed the impact of MSCs on sympathetic nerves via mitochondria exchange. In conclusion, iPSC-derived MSCs may provide a novel option to manage perimenopause-related hormonal dysregulation and neurological disorders during the female aging process.

Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing.

Male reproductive system ageing is closely associated with deficiency in testosterone production due to loss of functional Leydig cells, which are differentiated from stem Leydig cells (SLCs). However, the relationship between SLC differentiation and ageing remains unknown. In addition, active lipid metabolism during SLC differentiation in the reproductive system requires transportation and processing of substrates among multiple organelles, e.g., mitochondria and endoplasmic reticulum (ER), highlighting the importance of interorganelle contact. Here, we show that SLC differentiation potential declines with disordered intracellular homeostasis during SLC senescence. Mechanistically, loss of the intermediate filament Nestin results in lower differentiation capacity by separating mitochondria-ER contacts (MERCs) during SLC senescence. Furthermore, pharmacological intervention by melatonin restores Nestin-dependent MERCs, reverses SLC differentiation capacity and alleviates male reproductive system ageing. These findings not only explain SLC senescence from a cytoskeleton-dependent MERCs regulation mechanism, but also suggest a promising therapy targeting SLC differentiation for age-related reproductive system diseases.

Nestin promotes pulmonary fibrosis via facilitating recycling of TGF-ß receptor I.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that is characterised by aberrant proliferation of activated myofibroblasts and pathological remodelling of the extracellular matrix. Previous studies have revealed that the intermediate filament protein nestin plays key roles in tissue regeneration and wound healing in different organs. Whether nestin plays a critical role in the pathogenesis of IPF needs to be clarified. METHODS: Nestin expression in lung tissues from bleomycin-treated mice and IPF patients was determined. Transfection with nestin short hairpin RNA vectors in vitro that regulated transcription growth factor (TGF)-ß/Smad signalling was conducted. Biotinylation assays to observe plasma membrane TßRI, TßRI endocytosis and TßRI recycling after nestin knockdown were performed. Adeno-associated virus serotype (AAV)6-mediated nestin knockdown was assessed in vivo. RESULTS: We found that nestin expression was increased in a murine pulmonary fibrosis model and IPF patients, and that the upregulated protein primarily localised in lung α-smooth muscle actin-positive myofibroblasts. Mechanistically, we determined that nestin knockdown inhibited TGF-ß signalling by suppressing recycling of TßRI to the cell surface and that Rab11 was required for the ability of nestin to promote TßRI recycling. In vivo, we found that intratracheal administration of AAV6-mediated nestin knockdown significantly alleviated pulmonary fibrosis in multiple experimental mice models. CONCLUSION: Our findings reveal a pro-fibrotic function of nestin partially through facilitating Rab11-dependent recycling of TßRI and shed new light on pulmonary fibrosis treatment.

A Comparative Analysis of the Gene Expression Profiles of Small Cell Esophageal Carcinoma, Small Cell Lung Cancer, and Esophageal Adeno/Squamous Carcinoma.

Purpose/objectives: Primary small cell esophageal carcinoma (SCEC) is a rare malignancy without an established treatment strategy. This study investigated the gene expression profile of SCEC and compared it with the expression profiles of small cell lung cancer (SCLC) and esophageal adeno/squamous carcinoma (EAC/ESCC). Materials/methods: All patients with SCEC, SCLC, and EAC/ESCC in the Surveillance, Epidemiology, and End Results (SEER) database 1973-2014 were included. Overall survival (OS) and prognostic analysis were conducted. De novo expression array analysis was performed on three pairs of frozen primary SCEC tissues and the corresponding normal samples from the institutional tissue bank using the Affymetrix HG U133 plus 2.0 Array. These data were complemented with public domain expression data sets from the Gene Expression Omnibus (GEO) repository using the same working platforms, which included primary SCLC, EAC/ESCC, and normal lung/esophagus specimens (series GSE30219 and GSE26886). After individual normalization, the primary tumors were submitted to statistical analysis (GeneSpring GX 13.0) to identify the differentially expressed genes (DEGs) relative to their paired normal tissues. Enrichments of genes categorized by function and gene interactions were analyzed by DAVID 6.8 and STRING 11.0, respectively. Results: The clinical outcomes of the patients with SCEC were significantly more worse than those with EAC/ESCC and SCLC in the SEER database. SCEC had more DEGs in common with SCLC than EAC/ESCC [829 vs. 450; false discovery rate (FDR) < 0.01; and fold change ≥2], leading to a stronger correlation between SCEC and SCLC (Pearson's correlation coefficient was 0.60 for SCEC vs. SCLC, 0.51 or 0.45 for SCEC vs. ESCC or EAC, and the coefficient was 0.73 for ESCC vs. EAC). Similar findings were obtained by principal component analysis (PCA) using all DEGs retrieved from these four groups. Functional annotation showed that a higher proportion of pathways and biological processes were common between SCEC and SCLC and were associated with the cell cycle (mitosis), DNA replication, telomere maintenance, DNA repair, and P53 and RB pathways (Benjamini p < 0.05). Compared with EAC/ESCC, SCEC shared more co-upregulated DEGs coding for the aforementioned common pathways with SCLC (584 vs. 155). In addition, SCEC and SCLC were found to have possessed overlapping gene-interactive networks, with centromere protein F (CENPF), never in mitosis gene A-related kinase 2 ( NEK2), kinesin family member 11 (KIF11), thymopoietin (TMPO), and forkhead box protein M1 (FOXM1) as common skeletons centered by gene regulatory network (NUF2). Conclusions: This study is the first attempt to examine the genomic signatures of SCEC at the transcriptomic level and compare the expression profiles between SCEC, SCLC, and EAC/ESCC. Our preliminary data indicate that SCEC and SCLC display notably similar patterns of gene expression for mitosis and DNA repair. Further validation studies are warranted.

Choice of Treatment for Patients With Non-small-cell Lung Cancer >5 cm Between Surgery Alone and Surgery Plus Adjuvant Radiotherapy.

Background: According to the lung cancer staging project, T2b (>5-7 cm) and T3 (>7 cm) non-small cell lung cancers (NSCLC) should be reclassified into T3 and T4 groups. The objective of this study was to evaluate the effect of surgery alone or surgery plus adjuvant radiation (SART) on survival of node-negative patients with NSCLC >5 cm. Methods: We identified 4557 N0 patients with NSCLC >5 cm in the Surveillance, Epidemiology, and End Results database from 2004 to 2014. Overall survival (OS) and cancer-specific survival (CSS) were compared among patients who underwent surgery alone and SART. The proportional hazards model was applied to evaluate multiple prognostic factors. Results: 1,042 and 525 patients who underwent surgery alone and SART, respectively were enrolled after propensity-score matching. OS and CSS favored surgery alone rather than SART. Multivariate analysis showed that the number of lymph nodes examined more than six was associated with better OS and CSS for NSCLC >5 cm, especially in patients treated with surgery alone. Lobectomy should be recommended as the primary option for NSCLC >5 to 7 cm, whereas its superiority was not significant over sublobectomy for NSCLC >7 cm. Conclusion: Surgery alone should be recommended as the first choice for patients with NSCLC >5 cm. The number of examined lymph nodes should be more than six in patients with NSCLC >5 cm, especially for those who undergo surgery alone. For patients with NSCLC >7 cm who could not tolerate lobectomy, sublobectomy might be an alternative surgical procedure.

Inhibition of TGFß improves hematopoietic stem cell niche and ameliorates cancer-related anemia.

BACKGROUND: Cancer cachexia is a wasting syndrome that is quite common in terminal-stage cancer patients. Cancer-related anemia is one of the main features of cancer cachexia and mostly results in a poor prognosis. The disadvantages of the current therapies are obvious, but few new treatments have been developed because the pathological mechanism remains unclear. METHODS: C57BL/6 mice were subcutaneously injected with Lewis lung carcinoma cells to generate a cancer-related anemia model. The treated group received daily intraperitoneal injections of SB505124. Blood parameters were determined with a routine blood counting analyzer. Erythroid cells and hematopoietic stem/progenitor cells were analyzed by flow cytometry. The microarchitecture changes of the femurs were determined by micro-computed tomography scans. Smad2/3 phosphorylation was analyzed by immunofluorescence and Western blotting. The changes in the hematopoietic stem cell niche were revealed by qPCR analysis of both fibrosis-related genes and hematopoietic genes, fibroblastic colony-forming unit assays, and lineage differentiation of mesenchymal stromal cells. RESULTS: The mouse model exhibited hematopoietic suppression, marked by a decrease of erythrocytes in the peripheral blood, as well as an increase of immature erythroblasts and reduced differentiation of multipotent progenitors in the bone marrow. The ratio of bone volume/total volume, trabecular number, and cortical wall thickness all appeared to decrease, and the increased osteoclast number has led to the release of latent TGFß and TGFß signaling over-activation. Excessive TGFß deteriorated the hematopoietic stem cell niche, inducing fibrosis of the bone marrow as well as the transition of mesenchymal stromal cells. Treatment with SB505124, a small-molecule inhibitor of TGFß signaling, significantly attenuated the symptoms of cancer-related anemia in this model, as evidenced by the increase of erythrocytes in the peripheral blood and the normalized proportion of erythroblast cell clusters. Meanwhile, hindered hematopoiesis and deteriorated hematopoietic stem cell niche were also shown to be restored with SB505124 treatment. CONCLUSION: This study investigated the role of TGFß released by bone remodeling in the progression of cancer-related anemia and revealed a potential therapeutic approach for relieving defects in hematopoiesis.

Effects of TiO2 doping on the performance of thermochemical energy storage based on Mn2O3/Mn3O4 redox materials.

A thermochemical energy storage (TCES) system can adjust problems of unstable energy supply for solar concentrating power plants. Mn2O3/Mn3O4 system is a promising TCES system, but it has the problem of a difficult reoxidation process. In this paper, TiO2 was doped into the manganese oxide TCES system to solve this problem and the factors which influence the performance of this method were analyzed. The different performances between commercial Mn2O3 (Mn) and Mn2O3 synthesized by the Pechini method (PCMn), and different scales of doping agents (25Ti, 100Ti) were compared. Because of the formation of the Mn2TiO4, adding TiO2 into the manganese oxide TCES system could improve its reoxidation process obviously. During single complete redox process, PCMn had better performance than Mn whether doped with TiO2 or not, but Mn had a higher optimum oxidation temperature and a narrow temperature range of the redox reactions after adding TiO2. Adding 25Ti could bring higher energy storage density than adding 100Ti, and the optimal doping ratio was 0.05. As the doping ratio of 25Ti was increased, the activation energy (E a) was increased and then decreased. The E a of the samples doped with 25Ti was higher than that doped with 100Ti. Moreover, the E a of the 25Mn0.05 was decreased firstly and then was increased in the later stage of the reaction. The doped Mn samples exhibited better performance and lower attenuation than the doped PCMn samples after 30 cycles. During cyclic tests, the Mn2TiO4 was initially formed at the boundary between Mn2O3 and TiO2, and it was generated continuously with the extension of operating time. Therefore, the operating temperature, morphology of the Mn2O3, the doping agents, the doping ratio, and the phase change with the operating time should be all considered when doping TiO2 into the Mn2O3/Mn3O4 TCES system to improve its performance. Moreover, the results obtained from Mn-Ti systems would make a lot sense when other similar systems are considered, such as Mn-Fe, Mn-Si, Mn-Cr, etc.

Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells.

BACKGROUND: Despite the high cure rate of T cell acute lymphoblastic leukemia (T-ALL), drug resistance to chemotherapy remains a significant clinical problem. Bone marrow mesenchymal stem cells (MSCs) protect leukemic cells from chemotherapy, but the underlying mechanisms are poorly understood. In this study, we aimed to uncover the mechanism of MSC-induced chemoresistance in T-ALL cells, thus providing a promising clinical therapy target. METHODS: Cell viability was determined using the viability assay kit CCK-8. The mitochondrial ROS levels were detected using the fluorescent probe MitoSOX™ Red, and fluorescence intensity was measured by flow cytometry. In vitro, MSCs and Jurkat cells were cocultured. MSCs were labeled with green fluorescent protein (GFP), and Jurkat cells were labeled with the mitochondria-specific dye MitoTracker Red. Bidirectional mitochondrial transfer was detected by flow cytometry and confocal microscopy. The mechanism of mitochondria transfer was analyzed by inhibitor assays. Transcripts related to Jurkat cell/MSC adhesion in the coculture system were assessed by qRT-PCR. After treatment with a neutralizing antibody against a key adhesion molecule, mitochondria transfer from Jurkat cells to MSCs was again detected by flow cytometry and confocal microscopy. Finally, we verified our findings using human primary T-ALL cells cocultured with MSCs. RESULTS: Chemotherapeutic drugs caused intracellular oxidative stress in Jurkat cells. Jurkat cells transfer mitochondria to MSCs but receive few mitochondria from MSCs, resulting in chemoresistance. This process of mitochondria transfer is mediated by tunneling nanotubes, which are protrusions that extend from the cell membrane . Moreover, we found that most Jurkat cells adhered to MSCs in the coculture system, which was mediated by the adhesion molecule ICAM-1. Treatment with a neutralizing antibody against ICAM-1 led to a decreased number of adhering Jurkat cells, decreased mitochondria transfer, and increased chemotherapy-induced cell death. CONCLUSIONS: We show evidence that mitochondria transfer from Jurkat cells to MSCs, which is mediated by cell adhesion, may be a potential therapeutic target for T-ALL treatment.

Composition and abundance of microbiota in the pharynx in patients with laryngeal carcinoma and vocal cord polyps.

The pharynx is an important site of microbiota colonization, but the bacterial populations at this site have been relatively unexplored by culture-independent approaches. The aim of this study was to characterize the microbiota structure of the pharynx. Pyrosequencing of 16S rRNA gene libraries was used to characterize the pharyngeal microbiota using swab samples from 68 subjects with laryngeal cancer and 28 subjects with vocal cord polyps. Overall, the major phylum was Firmicutes, with Streptococcus as the predominant genus in the pharyngeal communities. Nine core operational taxonomic units detected from Streptococcus, Fusobacterium, Prevotella, Granulicatella, and Veillonella accounted for 21.3% of the total sequences detected. However, there was no difference in bacterial communities in the pharynx from patients with laryngeal cancer and vocal cord polyps. The relative abundance of Firmicutes was inversely correlated with Fusobacteria, Proteobacteria, Actinobacteria, and Bacteroidetes. The correlation was evident at the genus level, and the relative abundance of Streptococcus was inversely associated with Fusobacterium, Leptotrichia, Neisseria, Actinomyces, and Prevotella. This study presented a profile for the overall structure of the microbiota in pharyngeal swab samples. Inverse correlations were found between Streptococcus and other bacterial communities, suggesting that potential antagonism may exist among pharyngeal microbiota.

A flexible surface wetness sensor using a RFID technique.

This paper presents a flexible wetness sensor whose detection signal, converted to a binary code, is transmitted through radio-frequency (RF) waves from a radio-frequency identification integrated circuit (RFID IC) to a remote reader. The flexible sensor, with a fixed operating frequency of 13.56 MHz, contains a RFID IC and a sensor circuit that is fabricated on a flexible printed circuit board (FPCB) using a Micro-Electro-Mechanical-System (MEMS) process. The sensor circuit contains a comb-shaped sensing area surrounded by an octagonal antenna with a width of 2.7 cm. The binary code transmitted from the RFIC to the reader changes if the surface conditions of the detector surface changes from dry to wet. This variation in the binary code can be observed on a digital oscilloscope connected to the reader.