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Abstract Iron is an essential biomineral in the human body. Here, we describe a subset of iron-loaded cancer-associated fibroblasts, termed as FerroCAFs, that utilize iron to induce immunosuppression in prostate cancer and predict an unfavorable clinical outcome. FerroCAFs secrete myeloid cell-associated proteins, including CCL2, CSF1 and CXCL1, to recruit immunosuppressive myeloid cells. We report the presence of FerroCAFs in prostate cancer from both mice and human, as well as in human lung and ovarian cancers, and identify a conserved cell surface marker, the poliovirus receptor. Mechanistically, the accumulated iron in FerroCAFs is caused by Hmox1-mediated iron release from heme degradation. The intracellular iron activates the Kdm6b, an iron-dependent epigenetic enzyme, to induce an accessible chromatin state and transcription of myeloid cell-associated protein genes. Targeting the FerroCAFs by inhibiting the Hmox1/iron/Kdm6b signaling axis incurs anti-tumor immunity and tumor suppression. Collectively, we report an iron-loaded FerroCAF cluster that drives immunosuppression through an iron-dependent epigenetic reprogramming mechanism and reveal promising therapeutic targets to boost anti-tumor immunity.

Abstract Unintended pregnancy for female patients with chronic myeloid leukemia (CML) raises the discussion of treatment choices due to the teratogenicity of tyrosine kinase inhibitor (TKI). We report 51 accidental pregnant CML chronic phase (CP) patients with TKI withdrawal immediately after pregnancy from December 2010 to February 2024 to observe the effect of short exposure to TKI on the fetus and the infant outcomes. 59 pregnancies resulted in 100% normal childbirth without birth abnormalities. The median TKI exposure duration was 4 (4–20) weeks in 58 pregnancies, and one pregnancy avoided TKI exposure due to treatment discontinuation of the patient with treatment-free remission (TFR). All newborns had normal birth weight except one premature infant with low birth weight less than the 10th percentile. Up to now, all the children are in good health. 13 (25.5%) and 30 (58.8%) patients had achieved major molecular response (MMR) and deep molecular response (DMR) at pregnancy, respectively. After TKI discontinuation, loss of MMR and complete hematologic response occurred in 6 (46.2%) and 2 (25.0%) patients at delivery, respectively. 38 patients resumed TKI treatment after delivery, and 13 patients without DMR loss sustained TFR after delivery. The median time to regain MMR and DMR were 3 (2–6) months and 6 (1–28) months, respectively. These results demonstrate that TKI discontinuation during pregnancy is feasible for CML-CP patients, and short TKI exposure of pregnant patients has little influence on children’s growth and development.

As a new pollutant treatment technology, microbial fuel cell (MFC) has a broad prospect. In this article, the devices assembled using walnut shells are named biochar-microbial fuel cell (B-MFC), and the devices assembled using graphene are named graphene-microbial fuel cell (G-MFC). Under the condition of an external resistance of 1,000 Ω, the B-MFC with biochar as the electrode plate can generate a voltage of up to 75.26 mV. The maximum power density is 76.61 mW/m2, and the total internal resistance is 3,117.09 Ω. The removal efficiency of B-MFC for ammonia nitrogen (NH3-N), chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) was higher than that of G-MFC. The results of microbial analysis showed that there was more operational taxonomic unit (OTU) on the walnut shell biochar electrode plate. The final analysis of the two electrode materials using BET specific surface area testing method (BET) and scanning electron microscope (SEM) showed that the pore size of walnut shell biochar was smaller, the specific surface area was larger, and the pore distribution was smoother. The results show that using walnut shells to make electrode plates is an optional waste recycling method and an electrode plate with excellent development prospects. HIGHLIGHTS Preparation of electrode plates for microbial fuel cells using waste walnut shells.; The sewage treatment performance of the walnut shell biochar electrode plate has been improved.; Walnut shell biochar electrode plate is more suitable for microbial attachment and growth.;

Abstract Seipin is one key mediator of lipid metabolism that is highly expressed in adipose tissues as well as in the brain. Lack of Seipin gene, Bscl2, leads to not only severe lipid metabolic disorders but also cognitive impairments and motor disabilities. Myelin, composed mainly of lipids, facilitates nerve transmission and is important for motor coordination and learning. Whether Seipin deficiency-leaded defects in learning and motor coordination is underlined by lipid dysregulation and its consequent myelin abnormalities remains to be elucidated. In the present study, we verified the expression of Seipin in oligodendrocytes (OLs) and their precursors, oligodendrocyte precursor cells (OPCs), and demonstrated that Seipin deficiency compromised OPC differentiation, which led to decreased OL numbers, myelin protein, myelinated fiber proportion and thickness of myelin. Deficiency of Seipin resulted in impaired spatial cognition and motor coordination in mice. Mechanistically, Seipin deficiency suppressed sphingolipid metabolism-related genes in OPCs and caused morphological abnormalities in lipid droplets (LDs), which markedly impeded OPC differentiation. Importantly, rosiglitazone, one agonist of PPAR-gamma, substantially restored phenotypes resulting from Seipin deficiency, such as aberrant LDs, reduced sphingolipids, obstructed OPC differentiation, and neurobehavioral defects. Collectively, the present study elucidated how Seipin deficiency-induced lipid dysregulation leads to neurobehavioral deficits via impairing myelination, which may pave the way for developing novel intervention strategy for treating metabolism-involved neurological disorders.

Abstract Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m6A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m6A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m6A modification is increased during ferroptotic cell death and correlates with the decreased m6A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m6A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression.

ABSTRACT: Klebsiella pneumoniae is a serious pathogenic bacterium that poses a significant threat to young poultry and the cause of significant chick mortality and economic loss. We investigated the therapeutic efficacy of enrofloxacin in treating K. pneumoniae infections in chicks and employed an in vivo pharmacokinetic/pharmacodynamic (PK/PD) model. In vivo efficacy was evaluated using 6 multiple-dose groups (oral administration once a day for 3 d) and 2 single-dose groups (oral administration once only). The PK and PD parameters of plasma and lung were analyzed using PK/PD fitting analysis. K. pneumoniae administered intratracheally (108 CFU/mL in 0.4 mL saline) was used to establish a model for pulmonary infection. The plasma protein binding of enrofloxacin was 20.18%. Enrofloxacin displayed T1/2β values of 4.78 ± 0.69 h and 4.78 ± 1.02 h in plasma and lung of infected chicks, respectively. When the dosage in the multiple-dose group was > 10 mg/kg, bactericidal activity was found and complete eradication was not achieved when the dosage was ≤ 40 mg/kg. When TMSW was set at 20%, the calculated dosage and bacterial reduction (E) based on plasma free drug data were 4.03 mg/kg and -1.982 Log10 CFU/mL, respectively. In the calculation of PK/PD parameters for reducing 3 Log10 CFU/mL and using Cmax/MIC, AUC72h/MIC and TMSW of free drug in plasma values at 9.479, 379.691, and 44.395%, respectively, the value of AUC72h/MIC based on the concentration of drug in lung was 530.800. According to the fitting correlation R2, the PK/PD fitting results of free drug in plasma were better. The corresponding enrofloxacin dosage for AUC72h/MIC of the plasma free drug concentration was 14.16 mg/kg. The administration regimen corresponding to these dosages was once daily for 3 d. This dosage regimen (14.16 mg/kg) was relatively high compared to the clinically recommended dosage in China (7.5 mg/kg) when treating infections caused by K. pneumoniae with MIC ≥ 0.125 μg/mL, so careful consideration is needed.

Abstract The aim of this study was to examine the parenting characteristics of young patients with bipolar disorder (BD) and explore the sex differences. The parental rearing pattern of young patients with BD was measured and compared with the healthy control of young adults. The EMBU scale was used to assess parental rearing patterns. Patients with BD reported significantly higher scores in the punishment and severity index, as well as of the rejection and denial index, but lower scores in the warmth & affectionate index in the paternal rearing pattern, compared with healthy controls. In addition, patients scored higher on the punishment and severity index and rejection and patterns index in maternal rearing patterns. More importantly, we found significant sex differences in maternal rearing patterns (pBonferroni

Abstract Background Lipodystrophy-associated metabolic disorders caused by Seipin deficiency lead to not only severe lipodystrophy but also neurological disorders. However, the underlying mechanism of Seipin deficiency-induced neuropathy is not well elucidated, and the possible restorative strategy needs to be explored. Methods In the present study, we used Seipin knockout (KO) mice, combined with transcriptome analysis, mass spectrometry imaging, neurobehavior test, and cellular and molecular assay to investigate the systemic lipid metabolic abnormalities in lipodystrophic mice model and their effects on adult neurogenesis in the subventricular zone (SVZ) and olfactory function. After subcutaneous adipose tissue (AT) transplantation, metabolic and neurological function was measured in Seipin KO mice to clarify whether restoring lipid metabolic homeostasis would improve neurobehavior. Results It was found that Seipin KO mice presented the ectopic accumulation of lipids in the lateral ventricle, accompanied by decreased neurogenesis in adult SVZ, diminished new neuron formation in the olfactory bulb, and impaired olfactory-related memory. Transcriptome analysis showed that the differentially expressed genes (DEGs) in SVZ of adult Seipin KO mice were significantly enriched in lipid metabolism. Mass spectrometry imaging showed that the levels of glycerophospholipid and diglyceride (DG) were significantly increased. Furthermore, we found that AT transplantation rescued the abnormality of peripheral metabolism in Seipin KO mice and ameliorated the ectopic lipid accumulation, concomitant with restoration of the SVZ neurogenesis and olfactory function. Mechanistically, PKCα expression was up-regulated in SVZ tissues of Seipin KO mice, which may be a potential mediator between lipid dysregulation and neurological disorder. DG analogue (Dic8) can up-regulate PKCα and inhibit the proliferation and differentiation of neural stem cells (NSCs) in vitro, while PKCα inhibitor can block this effect. Conclusion This study demonstrates that Seipin deficiency can lead to systemic lipid disorder with concomitant SVZ neurogenesis and impaired olfactory memory. However, AT restores lipid homeostasis and neurogenesis. PKCα is a key mediator mediating Seipin KO-induced abnormal lipid metabolism and impaired neurogenesis in the SVZ, and inhibition of PKCα can restore the impaired neurogenesis. This work reveals the underlying mechanism of Seipin deficiency-induced neurological dysfunction and provides new ideas for the treatment of neurological dysfunction caused by metabolic disorders.

Background: The application of ferric citrate therapy has yielded unexpected benefits in recent years for Chronic kidney disease patients suffering from hyperphosphatemia and iron deficiency -anaemia. Despite this, earlier research on the impact of ferric citrate on NDD-CKD has been contentious.Objective: The goal of the meta-analysis is to evaluate the evidence regarding the advantages and dangers of ferric citrate for the treatment of hyperphosphatemia and iron deficiency anaemia in NDD-CKD patients.Methods: Between the start of the study and June 2022, we searched PubMed, Embase, Cochrane, EBSCO, Scopus, Web of Science, Wan Fang Data, CNKI, and VIP databases for randomised controlled trials of iron citrate for hyperphosphatemia and anaemia in patients with NDD-CKD. For binary categorical data, risk ratios (OR) were employed, and for continuous variables, weighted mean differences The effect sizes for both count and measurement data were expressed using 95% confidence intervalsResults: The meta-analysis includes eight trials with a total of 1281 NDD-CKD patients. The phosphorus-lowering effect of ferric citrate was greater compared to the control group (WMD, −0.55, 95% CI, −0.81 to −0.28; I2 = 86%, p < 0.001). Calcium (WMD, 0.092; 95% CI, −0.051 to 0.234; p > 0.05; I2 = 61.9%), PTH (WMD, −0.10; 95% CI, −0.44 to 0.23; I2 = 75%, p > 0.05) and iFGF23 (WMD, −7.62; 95% CI, −21.18 to 5.94; I2 = 20%, p > 0.05) levels were not statistically different after ferric citrate treatment compared to control treatment. Furthermore, ferric citrate increased iron reserves and haemoglobin. The ferric citrate group had considerably greater levels than the controls. Ferric citrate, on the other hand, may raise the risk of constipation, diarrhoea, and nausea.Conclusion: This meta-analysis found that ferric citrate had a beneficial effect in the treatment of NDD-CKD, particularly in reducing blood phosphorus levels when compared to a control intervention. It also shown that ferric citrate has a favourable effect on iron intake and anaemia management. In terms of safety, ferric citrate may increase the likelihood of gastrointestinal side effects.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Abstract Metabolic status is essential in maintaining normal functions of hematopoietic stem cells (HSCs). However, how the dynamic of the mitochondrion, as a central organelle in metabolism, is molecularly regulated to orchestrate metabolism and HSC stemness remains to be elucidated. Here, we focus on the role of Zeb1, a well-characterized epithelial-to-mesenchymal transition (EMT) inducer which has been demonstrated to confer stem-cell-like characteristics in multiple cancer types in stemness regulation of HSCs. Using a Zeb1-tdTomato reporter mouse model, we find that Zeb1+Lin−Sca-1+c-Kit+ cells (Zeb1+-LSKs) represent a subset of functional long-term HSCs. Zeb1+LSKs exhibit a reduced reactive oxygen species (ROS) level, low mitochondrial mass, low mitochondrial membrane potential (MMP), and particularly small, round fragmented mitochondria. Of note, ectopic expression of Zeb1 leads to a fragmented mitochondrial morphology with a low mitochondrial metabolic status in EML cells. In addition, Zeb1-knockout (Zeb1-KO) LSKs from fetal liver display an exhausted stem-cell activity. Zeb1 deficiency results in elongated and tubulated mitochondria with increased mitochondrial mass, elevated MMP, and higher ROS production. Mechanistically, Zeb1 acts as a transcriptional suppressor on the key mitochondrial-fusion protein Mitofusin-2 (encoded by Mfn2). We highlight an important role of Zeb1 in the regulation of mitochondrial morphology in HSC and the metabolic control of HSC stemness by repressing Mfn2-mediated mitochondrial fusion.

Abstract Great attention is paid to the role of androgen receptor (AR) as a central transcriptional factor in driving the growth of prostate cancer (PCa) epithelial cells. However, the understanding of the role of androgen in PCa‐infiltrated immune cells and the impact of androgen deprivation therapy (ADT), the first‐line treatment for advanced PCa, on the PCa immune microenvironment remains limited. On the other hand, immune checkpoint blockade has revolutionized the treatment of certain cancer types, but fails to achieve any benefit in advanced PCa, due to an immune suppressive environment. In this study, it is reported that AR signaling pathway is evidently activated in tumor‐associated macrophages (TAMs) of PCa both in mice and humans. AR acts as a transcriptional repressor for IL1B in TAMs. ADT releases the restraint of AR on IL1B and therefore leads to an excessive expression and secretion of IL‐1β in TAMs. IL‐1β induces myeloid‐derived suppressor cells (MDSCs) accumulation that inhibits the activation of cytotoxic T cells, leading to the immune suppressive microenvironment. Critically, anti‐IL‐1β antibody coupled with ADT and the immune checkpoint inhibitor anti‐PD‐1 antibody exerts a stronger anticancer effect on PCa following castration. Together, IL‐1β is an important androgen‐responsive immunotherapeutic target for advanced PCa.

BackgroundWhether autologous hematopoietic stem cell transplantation (ASCT) improves the survival of patients with peripheral T-cell lymphoma (PTCL) remains controversial. Some studies have demonstrated that the efficacy of ASCT is superior in patients with complete remission (CR), whereas patients with partial remission (PR) remain vulnerable to relapse after ASCT, resulting in decreased survival rates. Maintenance therapy after chemotherapy may reduce the relapse rate of PTCL and improve survival; however, the role of maintenance therapy after ASCT in PTCL remains unclear. In this study, we aimed to analyze the efficacy of ASCT and post-transplant maintenance therapy in PTCL.MethodsWe retrospectively analyzed the clinical data of 69 patients with PTCL who underwent ASCT at our center between November 2001 and November 2021. According to the patients’ intention, thirty patients received post-transplant maintenance treatment, whereas 39 did not. The overall survival (OS) and progression-free survival (PFS) between the groups were compared using the log-rank test.ResultsAt a median follow-up of 36 months, the entire cohort’s 3-year OS and PFS were 67.8% and 53.0%, respectively. The 3-year OS and PFS of patients with CR1, CR2, and PR were 85.3% and 65.4%, 80.0% and 60.0%, and 38.4% and 32.0%, respectively (OS: P=0.001; PFS: P=0.003). The relapse rates between the groups with or without maintenance therapy were 26.7% vs. 52.2%, the 3-year OS was 86.0% vs. 54.2% (P=0.004), and the 3-year PFS was 73.3% vs. 37.5% (P=0.004). Further analysis revealed that the efficacy of maintenance therapy was not significant in patients with CR1 and CR2, whereas patients with PR benefited from maintenance therapy. The relapse rate of patients with PR who received or did not receive maintenance therapy was 33.3% vs. 78.7%, 3-year OS was 66.7% vs. 21.9% (P=0.007), and 3-year PFS was 66.7% vs. 12.5% (P=0.004).ConclusionsPatients with CR in PTCL benefit from ASCT, and post-transplant maintenance therapy reduces the relapse rate and significantly improves OS and PFS in patients with PR.

Using MODIS NDVI and meteorological data during 2000 -2019， this paper systematically analyzes the vegetation cover change and its response to climate in Three-River-Source National Park from the aspects of temporal scale， correlation， linear trend， etc.The results show that： （1） the vegetation coverage area of the Three-River-Source National Park accounted for 85.38%， with the mean coverage of 42.70%， and the spatial distribution of vegetation coverage is increasing from northwest south to southeast.The vegetation coverage of the Yangtze River Source area is low， while the Yellow River Source area is medium， and the Lancang River Source area by high vegetation coverage.（2）From 2000 to 2019， the vegetation covered area of Three-River-Source National Park have increased significantly， with the rate of 227.55 km2·a-1（P

Summary: Cell plasticity and neuroendocrine differentiation in prostate and lung adenocarcinomas are one of the major reasons for therapeutic resistance to targeted therapy. Whether and how metabolic changes contribute to this adenocarcinoma-to-neuroendocrine cell fate transition remains largely unclear. Here we show that neuroendocrine prostate or lung cancer cells possess mostly fragmented mitochondria with low membrane potential and rely on glycolysis for energy metabolism. We further show an important role of the cell fate determinant Numb in mitochondrial quality control via binding to Parkin and facilitating Parkin-mediated mitophagy. Deficiency in the Numb/Parkin pathway in prostate or lung adenocarcinomas causes a metabolic reprogramming featured with a significant increase in production of lactate acid, which subsequently leads to an upregulation of histone lactylation and transcription of neuroendocrine-associated genes. Collectively, the Numb/Parkin-directed mitochondrial fitness is a key metabolic switch and a promising therapeutic target on cancer cell plasticity through the regulation of histone lactylation.

Background: In clinical studies, some patients who achieve deep molecular response (DMR) can successfully discontinue tyrosine kinase inhibitor (TKI). TKI dose reduction is also an important aspect of alleviating adverse effects and improving quality of life. This study aimed to explore the outcome after drug withdrawal in Chinese CML patients.Methods: We conducted a retrospective analysis of the outcome of 190 patients who stopped TKI. 27 patients experienced dose reduction before TKI discontinuation. The median duration of TKI treatment and MR4 before discontinuation was 82 months and 61 months.Results: With median follow-up after stopping TKI treatment of 17 months, the estimated TFR (Treatment Free Remission) were 76.9% (95%CI, 70.2%–82.4%), 68.8% (95%CI, 61.3%–75.2%), and 65.5% (95%CI, 57.4%–72.5%) at 6, 12 and 24 months. For full-dose and low-dose TKI groups, the TFR at 24 months was 66.7% and 55.8% (p = 0.320, log-rank). Most patients (56/57) quickly achieved MMR after restarting TKI treatment. Multivariable analysis showed that patients with TKI resistance had a higher risk of molecular relapse than patients without TKI resistance (p < 0.001).Conclusion: TFR rates were not impaired in patients experiencing dose reduction before TKI discontinuation compared to patients with full-dose TKI. Our data on Chinese population may provide a basis for the safety and feasibility of TKI discontinuation, including discontinuation after dose reduction, in clinical practice.

To screen and evaluate excellent blackberry cultivars and strains, 17 indexes of plant growth and fruit horticultural and nutritional characteristics were measured, 20 simple sequence repeat (SSR) markers were analyzed, the fingerprints of 23 blackberry cultivars and strains were constructed, and the processing characteristics of 10 excellent cultivars and strains were evaluated. The results showed that ‘Chester’ and ‘Shuofeng’ had the highest plant yield (6.5 kg per plant), of which the ‘Chester’ fruit also had the highest hardness (2.78 kg/cm2). ‘Kiowa’ had the highest single fruit weight (10.43 g). ‘10-5n-2’ had the highest total anthocyanin content (225.4 mg/100 g FW) and total polyphenol content (3.24 mg/g FW), but a low plant yield. These results suggest that ‘Shuofeng’ and ‘Chester’ are the top two blackberry cultivars planted in Nanjing, with the best growth and comprehensive quality. Moreover, a total of 119 alleles were detected with an average number of 6 alleles per locus. The polymorphism information content (PIC) was 0.374~0.844, with an average of 0.739, indicating a high genetic diversity among the 23 blackberry cultivars and strains. This study provides insight into the plant growth, fruit characteristics and genetic diversity of the 23 blackberry cultivars and strains, and is thus conducive to the protection and utilization of blackberry cultivars and strains.

Abstract Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) is a progressive autosomal dominant neurodegenerative disease caused by abnormal CAG repeats in the exon 10 of ATXN3. The accumulation of the mutant ataxin-3 proteins carrying expanded polyglutamine (polyQ) leads to selective degeneration of neurons. Since the pathogenesis of SCA3 has not been fully elucidated, and no effective therapies have been identified, it is crucial to investigate the pathogenesis and seek new therapeutic strategies of SCA3. Induced pluripotent stem cells (iPSCs) can be used as the ideal cell model for the molecular pathogenesis of polyQ diseases. Abnormal CAG expansions mediated by CRISPR/Cas9 genome engineering technologies have shown promising potential for the treatment of polyQ diseases, including SCA3. In this study, SCA3-iPSCs can be corrected by the replacement of the abnormal CAG expansions (74 CAG) with normal repeats (17 CAG) using CRISPR/Cas9-mediated homologous recombination (HR) strategy. Besides, corrected SCA3-iPSCs retained pluripotent and normal karyotype, which can be differentiated into a neural stem cell (NSCs) and neuronal cells, and maintained electrophysiological characteristics. The expression of differentiation markers and electrophysiological characteristics were similar among the neuronal differentiation from normal control iPSCs (Ctrl-iPSCs), SCA3-iPSCs, and isogenic control SCA3-iPSCs. Furthermore, this study proved that the phenotypic abnormalities in SCA3 neurons, including aggregated IC2-polyQ protein, decreased mitochondrial membrane potential (MMP) and glutathione expressions, increased reactive oxygen species (ROS), intracellular Ca2+ concentrations, and lipid peroxidase malondialdehyde (MDA) levels, all were rescued in the corrected SCA3-NCs. For the first time, this study demonstrated the feasibility of CRISPR/Cas9-mediated HR strategy to precisely repair SCA3-iPSCs, and reverse the corresponding abnormal disease phenotypes. In addition, the importance of genetic control using CRISPR/Cas9-mediated iPSCs for disease modeling. Our work may contribute to providing a potential ideal model for molecular mechanism research and autologous stem cell therapy of SCA3 or other polyQ diseases, and offer a good gene therapy strategy for future treatment.

We investigate the Moiré superlattice structures generated by the interplay between vortex lattice and optical lattice in two-component Bose–Einstein condensates. Square vortex lattices are generated in both components of the rapidly rotating condensates, and an optical lattice with the same geometry as the vortex lattice is acted on the condensates for a short interval. The optical lattice provides a sudden phase imprint, leading to the appearance of a transient phonon lattice. Such lattice, combined with vortex lattice and twisted an angle from each other, results in the generation of transient Moiré superlattice. The possible superlattice patterns under different twist angles are studied, and the corresponding vertex spacing is determined. We also study the relative shift of the Moir é superlattices in two components of the condensates and give the corresponding shift vector. Our results enrich the quantum phases in cold atomic systems, and contribute to the understanding of Moiré physics in these systems.

Abstract This study aimed to observe the safety and clinical efficacy of early application of ruxolitinib to prevent acute graft-versus-host disease (aGVHD) after alternative donor transplantation in acute leukemia. There were 57 patients undergoing allo-HSCT at the Affiliated Cancer Hospital of Zhengzhou University from July 2017 to October 2019. They were divided into control(16 patients) and ruxolitinib (41 patients) groups. For aGVHD prophylaxis, the control group received post-transplantation cyclophosphamide, antithymocyte globulin-Fresenius, cyclosporine A, and mycophenolate mofetil, while in the ruxolitinib group, ruxolitinib 5 mg/d in adults or 0.07–0.1 mg/(kg d) in children was administered from the day of neutrophil engraftment to 100 days post-transplantation based on control group. We found 55 patients had successful reconstitution of hematopoiesis; No significant difference was found in cGVHD, hemorrhagic cystitis, pulmonary infection, intestinal infection, Epstein-Barr virus infection, cytomegalovirus infection, relapse, death, and nonrelapse mortality. The incidences of aGVHD (50 vs. 22%, P = 0.046) and grade II–IV aGVHD (42.9 vs. 12.2%, P = 0.013) were significantly higher in the control group than in the ruxolitinib group. No significant differences were observed in overall survival (P = 0.514), disease-free survival (P = 0.691), and cumulative platelet transfusion within 100 days post-transplantation between two groups. This suggests early application of ruxolitinib can reduce the incidence and severity of aGVHD and patients are well tolerated.

Abstract Background Neural stem cell (NSC) therapy remains one of the most potential approaches for the treatment of neurological disorders. The discovery of human induced pluripotent stem cells (hiPSCs) and the establishment of hiPSC-derived human neural stem cells (hiNSCs) have revolutionized the technique of cell therapy. Meanwhile, it is often required that NSCs are stored and transported to a long distance for research or treatment purposes. Although high survival rates could be maintained, conventional methods for cell transportation (dry ice or liquid nitrogen) are inconvenient and expensive. Therefore, the establishment of a safe, affordable, and low-cost strategy to store and transport easily accessible hiPSCs and hiNSCs, with characteristics that match fetal hNSCs, is incredibly urgent. Methods We reprogrammed human urinary cells to iPSCs using a non-integrating, virus-free technique and differentiated the iPSCs toward iNSCs/neurospheres and neurons, under Good Manufacturing Practice (GMP)-compatible conditions. The pluripotency of iPSCs and iNSCs was characterized by a series of classical methods (surface markers, karyotype analysis, and in vitro as well as in vivo differentiation capabilities, etc.). Results Here, our results showed that we successfully generated hiNSCs/neurospheres from more available, non-invasive, and more acceptable urinary cells by a virus-free technique. Next, we demonstrated that the iNSCs differentiated into mature cerebral cortical neurons and neural networks. Interestingly, hiNSCs survived longer as neurospheres at ambient temperature (AT) than those cultured in a monolayer. Within 7 days approximately, the neural viability remained at > 80%, while hiNSCs cultured in a monolayer died almost immediately. Neurospheres exposed to AT that were placed under standard culture conditions (37 °C, 5% CO2) recovered their typical morphology, and retained their proliferation and differentiation abilities. Conclusions In this study, we provided a simple method for the storage of NSCs as neurospheres at AT as an alternative method to more costly and inconvenient traditional methods of cryopreservation. This will enable hiNSCs to be transported over long distances at AT and facilitate the therapeutic application of NSCs as neurospheres without any further treatment.

Abstract Posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis is an effective strategie for patients receiving matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and haploidentical HSCT (haplo-HSCT). We evaluated the effectiveness and safety of reduced-dose cyclophosphamide, 20 mg/kg for 13 patients in MSD-HSCT cohort and 25 mg/kg for 22 patients in haplo-HSCT cohort, on days + 3, + 4 combined with cotransplantation of peripheral blood stem cells (PBSCs) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for severe aplastic anemia (SAA). In MSD-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the MSD-control cohort (P

Network pharmacology, as a novel way using bioinformatics to explore drug targets and interactions in cancer, broadens our understanding of drug action, thereby facilitating drug discovery. Here, we utilized network pharmacology to explore the role and mechanism by which cinobufotalin functions in colon adenocarcinoma (COAD). We found that cinobufotalin represses the growth and proliferation of colon cancer cells, and integrated public databases for targets reported to be associated with COAD, together with those predicted to be targets of cinobufotalin. Targets overlapped between COAD-associated proteins and cinobufotalin target proteins were used to filter candidate targets of cinobufotalin in COAD. The following proteins were thought to occupy a key position in COAD-cinobufotalin target networks: SRC, PIK3R1, MAPK1, PIK3CA, HSP90AA1, CTNNB1, GRB2, RHO1, PTPN11, and EGFR. The networks regulated by cinobufotalin were involved mainly in extracellular signal stimulation and transduction, including MAPK signaling pathway, PI3K-AKT signaling pathway, and JAK-STAT signaling pathway. Besides, transcriptome sequencing results also indicated that cinobufotalin inhibits the response of colon cancer cells to extracellular stimulation and promotes cell apoptosis. Molecular docking results showed that cinobufotalin matches in the pocket of the top candidate cinobufotalin target proteins (SRC, PIK3R1, MAPK1 and PIK3CA). These findings demonstrate cinobufotalin can be developed as potential anti-cancer therapeutics.

Heterogeneous populations of basal cells in the prostate epithelium contain stem cells. Here the authors show that Zeb1 marks a pool of prostate epithelial stem cells that self-renew, generate prostate glandular structures with all 3 epithelial cell types and are required for prostate basal cell development.

Blackberries have high nutritional value and strong biological activities, such as antiproliferative activity. Anthocyanins are important functional components in blackberries. We collected 25 kinds (lines) of blackberries from our nursery to investigate antiproliferative agents in natural foods. Among them, the Shuofeng variety had the highest anthocyanin content, with 2.54 mg/g of fresh fruit, which increased to 357.75 mg/g of dried powder through ultrasound-assisted solvent extraction and macroporous resin adsorption. Additional experiments showed that Shuofeng’s anthocyanin content had high anti-HepG2 activity in vitro and in vivo, as well as activity against Hela (68.62 μg/mL), HepG2 (55.85 μg/mL), MCF-7 (181.21 μg/mL), and A549 cells (82.01 μg/mL), as determined by MTT assay. It also had no apparent toxic effects. The combination of DDP and DOX significantly enhanced the antiproliferative activity of the four cell lines. The IC50 value of Shuofeng’s anthocyanin content combined with DOX in HepG2 cells was the lowest at only 0.08 μg/mL, indicating that the combination of drugs had additive and synergistic effects. Shuofeng’s anthocyanin content might intercalate into DNA and alter or destroy DNA, causing apoptosis and inhibiting cell proliferation. Our results show that blackberry anthocyanins can inhibit the proliferation of cancer cells and their possible mechanisms. However, we must study the deeper mechanism and explore its targeting effects in the future.

Central nervous system (CNS) complications can occur in 9%–15% of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical manifestations of the CNS complications are non-specific, with most of them being disturbances of consciousness, convulsions, headaches, fever, and epilepsy, making it difficult to infer the cause of the complications based on clinical manifestations. We retrospectively analyzed the sensitivity and feasibility of metagenomic next generation sequencing (mNGS) in the diagnosis of CNS infections after allo-HSCT. Lumbar punctures were performed on 20 patients with CNS symptoms after receiving alternative donor HSCT(AD-HSCT) at the Affiliated Cancer Hospital of Zhengzhou University from February 2019 to December 2020, and their cerebrospinal fluid (CSF) was collected. The mNGS technique was used to detect pathogens in the CSF. Routine CSF testing, biochemical analyses, G experiments, GM experiments, ink staining, acid-fast staining, and bacterial cultures were carried out, and quantitative PCR (qPCR) tests were used to detect cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKPyV), and human alphaherpesvirus (HHV). A total of 29 tests were performed with 21 of them being positive. Of the five negative patients, three were diagnosed with a posterior reversible encephalopathy syndrome, one as having transplantation-associated thrombotic microangiopathy, and one with transient seizure caused by hypertension. Fifteen patients tested positive, of which four had single infections and eleven had mixed infections. Five cases of fungal infections, six cases of bacterial infections, and 13 cases of viral infections were detected. Among the 13 cases of viral infections, ten cases were CMV(HHV-5); three were BKPyV; two were Torque teno virus (TTV); Two were HHV-1,two were EBV(HHV4), and one each of HpyV5 and HHV-6B. Thirteen patients tested positive for virus while the qPCR detection method of 6 identical specimens were below the minimum detection limit(

The repertoire of adaptive immune receptor is generated by V(D)J recombination, somatic rearrangements of V, D and J gene segments, in the respective loci. Here the authors show that the deficiency of Setd2, a histone methyl transfer, impairs V(D)J recombination and induces severe developmental blocks in both T and B lineages.

Rice samples were collected at 560 sites in 15 provinces across China in areas without known point mercury (Hg) sources. Total mercury (THg) and methylmercury (MeHg) concentrations were analyzed in these rice samples for risk assessment. Relatively low THg and MeHg concentrations were found in the majority of the white rice samples with an overall mean of 4.74 (1.06–22.7) μg kg−1 and 0.682 (0.03–8.71) μg kg−1, respectively. The means (range of) THg concentration of rice in each geographical region were 5.23 (1.07–19.5) μg kg−1, 5.14 (1.06–17.2) μg kg−1, 4.45 (1.41–17.2) μg kg−1, 4.20 (1.48–19.4) μg kg−1, 3.49 (1.49–10.7) μg kg−1, and 4.53 (1.30–19.4) μg kg−1 in east, centre, south, southwest, northwest and northeast, China, respectively, and the corresponding values for MeHg concentrations were 0.898 (0.127–8.35) μg kg−1, 0.603 (0.207–2.48) μg kg−1, 0.516 (0.032–1.50) μg kg−1, 0.615 (0.050–5.03) μg kg−1, 0.704 (0.148–2.41) μg kg−1 and 0.565 (0.035–8.71) μg kg−1, respectively. Hg contents in rice across China were found to be at background levels. Both the probable daily intakes (PDIs) of inorganic Hg (IHg) and MeHg from rice consumption showed low risks for general population in the investigated regions. Keywords: Rice, Mercury, Methylmercury, Probable daily intake, Health risk

Lignin nanoparticles (LNP) with various morphologies could be prepared with solvent–antisolvent methods. However, the employed toxic chemicals limited its large-scale application. In this study, an extremely green method using only ethanol and water as solvent and antisolvent was reported. Besides, with the syringaldehyde (SA) addition and its anchoring action on the lignin particles, a forming process of the tailed structure was observed and resulted. Moreover, the improved electronegativity originating from the phenolic hydroxyl groups enhanced the size distribution uniformity, and the new absorption peaks at 1190 cm−1 demonstrated the involvement of SA in the LNP formation. Lastly, the tailed lignin nanoparticles (T-LNP) composited with, respectively, polyvinyl alcohol, chitosan, cellulose nanofibers, cationic etherified starch, and sodium alginate were successfully prepared. The outstanding UV-shielding and free radical scavenging properties in the above composites showed their great potential in wide applications in packaging materials.

Spinal cord injury (SCI) causes patients paralysis and hard to recover. The therapeutic effects of current clinical drugs are accompanied by side effects. In recent years, stem cell therapy has attracted the attention of researchers. Human umbilical cord mesenchymal stem cells (hucMSCs) have been widely used in various diseases due to their excellent paracrine function. TNF-stimulated gene 6 (TSG-6), a secretion factor of stem cells, may play an important role in hucMSCs in the treatment of SCI. So we conducted an experiment to explore its effect. We first observed that the expression of TSG-6 increased in SCI rats after injected with hucMSCs. Then, we used siRNA to knowdown the expression of TSG-6. We treated SCI rats with TSG-6-knockdown hucMSCs. Without TSG-6 expression, hucMSCs treatment made the tissue recovery worse and the number of Nissl bodies less. Meanwhile, neutrophils infiltrated more in the damaged parts. Our research also proved that TSG-6 may help demyelination recovering and alleviate astrocytes gathering in the injury sites. Our study revealed that hucMSCs secreted TSG-6 may decrease the degeneration of myelin sheath, reduce inflammation, decrease neuron loss and promote tissue repair. These results provided a new therapeutic factor for the treatment of SCI.

Urine epithelial cells were harvested from a 32-year old female patient with spinocerebellar ataxia type 3 (SCA3) and reprogrammed into induced pluripotent stem cells (iPSCs) by non-integration system. The SCA3 derived iPSCs line, CSUXHi005-A, maintained 76 CAG expansions in the ATXN3 gene, was characterized by the expression of pluripotency markers and normal karyotype. The newly generated iPSCs retain the ability to differentiate into three germ layers by teratoma test, which provide an ideal tool for disease modeling, drug screening, and cellular therapy.

Background: Simple febrile seizures (SFS) and epilepsy are common seizures in childhood. However, the mechanism underlying SFS is uncertain, and the presence of obvious variances in white matter (WM) integrity and glymphatic function between SFS and epilepsy remain unclear. Therefore, this study aimed to investigate the differences in WM integrity and glymphatic function between SFS and epilepsy.Material and Methods: We retrospectively included 26 children with SFS, 33 children with epilepsy, and 28 controls aged 6–60 months who underwent magnetic resonance imaging (MRI). Tract-based spatial statistics (TBSS) were used to compare the diffusion tensor imaging (DTI) metrics of WM among the above-mentioned groups. T2-weighted imaging (T2WI) was used to segment the visible Virchow-Robin space (VRS) through a custom-designed automated method. VRS counts and volume were quantified and compared among the SFS, epilepsy, and control groups. Correlations of the VRS metrics and seizure duration and VRS metrics and the time interval between seizure onset and MRI scan were also investigated.Results: In comparison with controls, children with SFS showed no significant changes in fractional anisotropy (FA), axial diffusivity (AD), or radial diffusivity (RD) in the WM (P > 0.05). Decreased FA, unchanged AD, and increased RD were observed in the epilepsy group in comparison with the SFS and control groups (P < 0.05). Meanwhile, VRS counts were higher in the SFS and epilepsy groups than in the control group (VRS_SFS, 442.42 ± 74.58, VRS_epilepsy, 629.94 ± 106.55, VRS_control, 354.14 ± 106.58; P < 0.001), and similar results were found for VRS volume (VRS_SFS, 6,228.18 ± 570.74 mm3, VRS_epilepsy, 9,684.84 ± 7,292.66mm3, VRS_control, 4,007.22 ± 118.86 mm3; P < 0.001). However, VRS metrics were lower in the SFS group than in the epilepsy group (P < 0.001). In both SFS and epilepsy, VRS metrics positively correlated with seizure duration and negatively correlated with the course after seizure onset.Conclusion: SFS may not be associated with WM microstructural disruption; however, epilepsy is related to WM alterations. Seizures are associated with glymphatic dysfunction in either SFS or epilepsy.

A humidity sensor is a crucial device in daily life; therefore, in the present study, a novel humidity sensor was designed to increase its specific surface area to improve its humid sensing capacity and conductivity. Titanium dioxide nanoparticles (TiNP) consisting of zero-dimensional nanospheres and one-dimensional nanotubes were prepared by anodic oxidation. Rod-shaped cellulose nanocrystals (CNCs) with average length and diameter of 60 nm and 800 nm, respectively, were obtained by enzymatic hydrolysis and high pressure homogenization. TiNP/CNC composite films exhibited superior hydrophilicity and large specific surface areas based on Fourier transform infrared spectroscopy and nitrogen adsorption–desorption results. The humidity sensing characteristics of sensors based on TiNP/CNC flexible composite films with varying contents of TiNP were investigated under a relative humidity range of 11–97%. The 6% TiNP/CNC-based humidity sensor exhibited high humidity response, rapid response/recovery speed, and high stability. Furthermore, the humidity sensing mechanism of TiNP/CNC composite films was analyzed based on the density functional theory. TiNP/CNC-based humidity sensors could be applied in flexible and wearable electronics.

Severe mycological epilepsy of infancy is a catastrophic disease with preferential dysfunction of interneurons, frequent episode rate, cognitive and sudden death. The disease is mainly caused by heterozygous loss-of-function mutation of SCN1A gene encoding α subunit of the sodium channel Nav1.1. To generate mutations in normal iPSC, Transcription activator-like effector nucleases was used to introduce the epilepsy-causing mutation A5768G into the endogenous locus of SCN1A gene. The gene editing induced pluripotent stem cell line and normal iPSC were obtained from the same donor to eliminate significantly the genetic background noise.

Dravet syndrome is an epileptic encephalopathy largely due to haploinsufficiency of the voltage-gated sodium channel Nav1.1 that is expressed primarily in GABAergic neurons. In order to distinguish the different subtypes, we used gene editing to introduce tdTomato gene into the genome of iPSCs to label the GABAergic neurons in the differentiated neuronal networks. The gene-edited cell line demonstrates normal karyotype, expresses the main pluripotency markers, and shows the presence of differentiation into the three embryonic germ layers in teratomas.

Background: As global healthcare system is overwhelmed by novel coronavirus disease (COVID-19), early identification of risks of adverse outcomes becomes the key to optimize management and improve survival. This study aimed to provide a CT-based pattern categorization to predict outcome of COVID-19 pneumonia.Methods: One hundred and sixty-five patients with COVID-19 (91 men, 4–89 years) underwent chest CT were retrospectively enrolled. CT findings were categorized as Pattern 0 (negative), Pattern 1 (bronchopneumonia pattern), Pattern 2 (organizing pneumonia pattern), Pattern 3 (progressive organizing pneumonia pattern), and Pattern 4 (diffuse alveolar damage pattern). Clinical findings were compared across different categories. Time-dependent progression of CT patterns and correlations with clinical outcomes, i.e.„ discharge or adverse outcome (admission to ICU, requiring mechanical ventilation, or death), with pulmonary sequelae (complete absorption or residuals) on CT after discharge were analyzed.Results: Of 94 patients with outcome, 81 (86.2%) were discharged, 3 (3.2%) were admitted to ICU, 4 (4.3%) required mechanical ventilation, 6 (6.4%) died. 31 (38.3%) had complete absorption at median day 37 after symptom onset. Significant differences between pattern-categories were found in age, disease severity, comorbidity and laboratory results (all P < 0.05). Remarkable evolution was observed in Pattern 0–2 and Pattern 3–4 within 3 and 2 weeks after symptom-onset, respectively; most of patterns remained thereafter. After controlling for age, CT pattern significantly correlated with adverse outcomes [Pattern 4 vs. Pattern 0–3 [reference]; hazard-ratio [95% CI], 18.90 [1.91–186.60], P = 0.012]. CT pattern [Pattern 3–4 vs. Pattern 0–2 [reference]; 0.26 [0.08–0.88], P = 0.030] and C-reactive protein [>10 vs. ≤ 10 mg/L [reference]; 0.31 [0.13–0.72], P = 0.006] were risk factors associated with pulmonary residuals.Conclusion: CT pattern categorization allied with clinical characteristics within 2 weeks after symptom onset would facilitate early prognostic stratification in COVID-19 pneumonia.

Dravet syndrome is a neurological disorder characterized by treatment-resistant polymorphic seizures, primarily caused by loss-of-function in the SCN1A gene. To develop an in vitro model of this disease, in a previously study we generated an induced pluripotent stem cell line from a 10-year-old boy carrying the NM_001165963.1:c.5768A to G (Q1923R) mutation in SCN1A. Using TALEN-mediated genome editing, we have now generated an isogenic control line in which the disease-causing mutation found in the epilepsy patient iPSCs was corrected, in order to eliminate the interference of different genetic backgrounds in future analyses.

Epilepsy is a neurological disorder, characterized by recurrent (two or more) epileptic seizures resulting from excessive and abnormal cortical neural activity.Fibroblasts were collected from a 10-year-old male with antecedent febrile seizures (PEFS+) and carrying a heterozygous A > G mutation of Nav1.1 α subunit gene. The induced USTCi001-A retained the mutation, expressed pluripotent markers, showed normal karyotype, and displayed in vitro differentiation potential toward cells of the three embryonic germ layers.

Spinocerebellar ataxia type 1 (SCA1) is a hereditary neurodegenerative disease caused by CAG repeated expansion in ATXN1 gene. We generated induced pluripotent stem cells (iPSCs) from the urine exfoliated epithelial cells of SCA1 patient by using the integration-free methods. The patient derived iPSCs retained the mutation (the 65 CAG expansion tracts in ATXN1 gene), displayed normal karyotypes, expressed pluripotency markers and had the potential to differentiate towards three germ layers in vivo. This type of stem cell model will be valuable for elucidating the pathological mechanism and screening potential drugs of SCA1.

BackgroundAs a pandemic, a most-common pattern resembled organizing pneumonia (OP) has been identified by CT findings in novel coronavirus disease (COVID-19). We aimed to delineate the evolution of CT findings and outcome in OP of COVID-19.Materials and methods106 COVID-19 patients with OP based on CT findings were retrospectively included and categorized into non-severe (mild/common) and severe (severe/critical) groups. CT features including lobar distribution, presence of ground glass opacities (GGO), consolidation, linear opacities and total severity CT score were evaluated at three time intervals from symptom-onset to CT scan (day 0-7, day 8-14, day > 14). Discharge or adverse outcome (admission to ICU or death), and pulmonary sequelae (complete absorption or lesion residuals) on CT after discharge were analyzed based on the CT features at different time interval.Results79 (74.5%) patients were non-severe and 103 (97.2%) were discharged at median day 25 (range, day 8-50) after symptom-onset. Of 67 patients with revisit CT at 2-4 weeks after discharge, 20 (29.9%) had complete absorption of lesions at median day 38 (range, day 30-53) after symptom-onset. Significant differences between complete absorption and residuals groups were found in percentages of consolidation (1.5% vs. 13.8%, P = 0.010), number of involved lobe > 3 (40.0% vs. 72.5%, P = 0.030), CT score > 4 (20.0% vs. 65.0%, P = 0.010) at day 8-14.ConclusionMost OP cases had good prognosis. Approximately one-third of cases had complete absorption of lesions during 1-2 months after symptom-onset while those with increased frequency of consolidation, number of involved lobe > 3, and CT score > 4 at week 2 after symptom-onset may indicate lesion residuals on CT.

Unbalanced inflammatory reactions and oxidative stress are inseparably interconnected, and both may play crucial roles in the pathophysiological mechanisms of preeclampsia (PE). In the published previous studies, we have genotyped for SNPs that related to inflammation (rs2227485, rs153109, rs17855750, rs2027432, rs2275913, rs763780, rs4819554, and rs13015714) and oxidative stress (rs1695, rs4680, rs1800566, rs4807542, rs713041, rs7579, rs230813, rs1004467, rs3824755, and rs9932581) to investigate whether these polymorphisms were associated with susceptibility to PE in a Chinese Han population. In this present study, we collected these data of experimental and clinical from above studies for haplotype analysis of inflammation-related SNPs in 631 PE patients and 720 normal pregnancy and oxidative stress-related SNPs in 342 PE patients and 457 normal pregnancies for susceptibility to PE. The data of genotype distribution and allele frequency comparisons after correction for multiple comparisons (P/8 or P/10) showed 2 among the 8 candidate inflammation-related SNPs have significant differences (rs2027432 genotype χ2=407.377,p0.9), and the GT and GC haplotypes of rs4807542 and rs713041 in GPX4 showed significant differences between the PE and control groups (χ2=5.143,p=0.0233,p

Tyrosine is an essential ketogenic and glycogenic amino acid for the human body, which means that tyrosine is not only involved in protein metabolism, but also participates in the metabolism of lipids and carbohydrates. The liver is an important place for metabolism of lipids, carbohydrates, and proteins. The metabolic process of biological macro-molecules is a basis for maintaining the physiological activities of organisms, but the cross-linking mechanism of these processes is still unclear. Here, we found that the tyrosine-metabolizing enzymes, which were specifically and highly expressed in the liver, were significantly down-regulated in hepatocellular carcinoma (HCC), and had a correlation with a poor prognosis of HCC patients. Further analysis found that the reduction of tyrosine metabolism would activate the cell cycle and promote cell proliferation. In addition, we also found that the solute carrier family 27 member 5 (SLC27A5) regulates the expression of tyrosine-metabolizing enzymes through nuclear factor erythroid 2-related factor 2 (NRF2). Therefore, the SLC27A5 and tyrosine-metabolizing enzymes that we have identified coordinate lipid and tyrosine metabolism, regulate the cell cycle, and are potential targets for cancer treatment.

In recent years, the prefabricated house industry has rapid development,.Because of fewer suppliers, higher demand transport scheme and complex quality test, the risks of construction engineering logistics links are relatively high. Studying how to effectively evaluate the risks of construction engineering logistics links is significant. According to the characteristics of the prefabricated house construction engineering, we analyse the construction engineering logistics risks and use the combined weights method to determine the weight of indexes which contains both subjective and objective factors, to improve the scientific value and the validity of the assessment. Based on credibility measure method, a new logistics risk evaluation model in prefabricated housing is established to estimate the risk during making prefabricated house construction engineering. The presented model can avoid the subjectivity of selecting the membership function and solve the problem of how to comprehensively assess the construction engineering logistics risk in a certain extent.

Autism spectrum disorder (ASD) is a neurological disorder with complex etiologies. In this study, urine cells were collected from a 16-year-old male with ASD and reprogrammed with the human SKOM transcription factors. The patient has a heterozygous C > T mutation of FCGR1B gene that was confirmed by sequencing analysis. The pluripotency was verified by gene expression and capacity of differentiation towards the three germ layers. This kind of iPSC will be valuable for further understanding the pathogenesis of ASD and help to develop drugs for treating ASD.

In mercury (Hg) contaminated areas of Asia, human exposure to toxic methyl-Hg (MeHg) through a rice-based diet of locally produced crop may pose a health threat. Alternative cropping system to rice in such areas would be most desirable. In this study, corn, the leading cereal source in the world with large biomass, was demonstrated to accumulate an insignificant amount of MeHg from the soil in its edible portion compared to that in rice, suggesting corn being a very competitive alternative crop. By examining Hg stable isotope composition, Hg in the aerial parts of corn was found to be mostly from the atmosphere. Maize cropping worldwide is estimated to be a discemible sink of atmospheric Hg with approximately 44 Mg Hg accumulated in each growing season on a yearly basis, most of which is from foliar uptake of atmospheric Hg and this amount is comparable to litterfall Hg observed in North America and Europe. It is thus recommended to use corn as a replacement of rice in highly Hg-contaminated areas for remediation of Hg pollution in the food supply.

Bilateral cerebral palsy (BCP) is a common movement disorder in children, which often results in lifelong motor disability. One main symptom of BCP is the limitation of hand function in everyday activities. However, the neuroanatomical basis of this prominent hand impairment is yet to discover. Recent advances mainly focus on the lesions of BCP, but the views on the atypical development of cortical parcellations are extremely lacking. Here, in our study, neuroimaging with network analysis was employed to evaluate the changes of structural covariance networks (SCNs) in BCP children. We aimed to elucidate the alteration of SCNs based on cortical thickness (CT), and to reveal the relationship of CT and hand function in the participants with BCP. SCNs were constructed using covariance between regional CT, which was acquired from T1-weighted images of 19 children with BCP and 19 demographically matched healthy controls (HCs). Compared with HCs, BCP children showed increased CT in several regions involving the bilateral areas (lateral occipital, lingual, and fusiform) and right areas (cuneus, pericalcarine, inferior temporal, middle temporal, superior temporal, and insula). Decreased CT was found in the left superior temporal and right superior parietal cortices. Global network analyses revealed significantly decreased normalized clustering and small-worldness in the BCP network. The area under the curve (AUC) of global network measures varied slightly between the BCP and HC networks. The resistance of the both SCNs to the target and random attack showed no significant difference. Also, the BCP foci (right superior temporal and subtemporal cortex) showed a significantly negative correlation between the CT and manual ability. In this work, we identified the CT-based SCNs changes in children with BCP. The abnormal topological organization of SCNs was revealed, indicating abnormal CT, incongruous development of structural wiring, destructive nodal profiles of betweenness, and moved hub distribution in BCP children. This may provide a neuroanatomical hallmark of BCP in the developing brain. Therefore, our results may not only reflect neurodevelopmental aberrations but also compensatory mechanisms.

The induced pluripotent stem cell (iPSC) line XHCSUi001-A generated from urine cells of a female spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) patient by using the integration-free methods. The induced XHCSUi001-A retained the disease-causing ATXN3 mutation, expressed pluripotency markers, exhibited a normal karyotype and retained the ability to differentiate into the three germ layers in-vitro and in-vivo. This newly induced iPSC line could be a potential tool for researching the disease-specific mechanisms and drug screening of SCA3/MJD.