[Preliminary efficacy and safety analysis of carrelizumab combined with apatinib in patients with middle-advanced liver cancer progressed after drug-eluting beads-transcatheter arterial chemoembolization].

Objective: To explore the preliminary clinical efficacy and safety of calerizumab combined with apatinib in the treatment of patients with middle-advanced liver cancer whose disease has progressed after drug-eluting beads-transcatheter arterial chemoembolization (D-TACE). Methods: A retrospective analysis of 23 patients with advanced liver cancer after D-TACE who were treated with carrelizumab combined with apatinib from April 2019 to July 2020 at Lianyungang First People's Hospital was carried out. There were 15 males and 8 females with a mean age of (62±9) years. The clinical efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECRST), and treatment-related adverse events were analyzed after treatment. Results: All the patients received D-TACE therapy with an average of (2.6±1.0) times, TACE-refractory tumor was observed in 7 patients, and distant metastasis was seen in 6 patients. The objective response rates after combined treatment of 1 month and 3 months were 47.8% and 60.9%, respectively. Disease control rate (DCR) was 73.9% and 78.3%, respectively; median progression-free survival (mPFS) was 126 days. Among 18 patients with alpha fatoprotein (AFP)>200 µg/L, the values before and after treatment of 2 months was (497±117) µg/L and (80±19) µg/L, respectively (P<0.05). Among 9 patients of vascular endothelial growth factor (VEGF)>142.2 ng/L, the values before and after treatment of 2 months was (154±51) ng/L and (57±19) ng/L, respectively (P<0.05). The incidence of treatment-related adverse events was 87.0% (20/23). All adverse reactions did not exceed grade 3 and could be controlled by symptomatic supportive treatment or reducing the dose of apatinib,and the serum aspartate aminotransferase (AST) level after treatment of 3 months[(77±33) U/L] was higher than that before treatment [(45±26) U/L] (P<0.05). Conclusion: For patients with advanced liver cancer after D-TACE, the treatment of carrelizumab combined with apatinib is effective and the adverse reactions are controllable.

[Transcriptome sequencing-based classification and quantification of IKZF1 transcript isoforms in B-cell acute lymphoblastic leukemia].

Objective: To classify and quantify IKZF1 mutant transcripts in B-cell acute lymphoblastic leukemia (B-ALL) by RNA sequencing (RNA-seq) and bioinformatics analysis. Methods: A cohort of 263 B-ALL cases was enrolled at Hebei Yanda Ludaopei Hospital from September 2018 to September 2020. An integrated bioinformatics pipeline was developed to adapt the classification and quantification of IKZF1 transcripts from RNA-seq and was applied to sequencing data of these cases. The IKZF1 mutant transcripts classified by RNA-seq analysis were compared with the qualitative reverse transcription PCR (RT-PCR). Results: IKZF1 mutant transcripts were identified in 53 B-ALL patients by RT-PCR and Sanger sequencing, among which IK6 and IK10 transcripts accounted for 67.9% (36/53) and 28.3% (15/53) respectively. Additionally, 2 patients were double positive for IK6 and IK10. RNA-seq analysis identified 51 patients with IKZF1 mutant transcripts. Compared with the RT-PCR result, the detection sensitivity and specificity of RNA-seq analysis reached 94.3% (50/53) and 99.5% (209/210), respectively. Among the 50 patients with IKZF1 mutant transcripts both in RNA-seq and RT-PCR analysis, the ratio of mutant transcripts to total IKZF1 transcripts in 6 patients was 0.14 (0.11, 0.35), which was significantly lower than that of the other 44 patients [0.88 (0.35, 0.97), Z=-3.945,P<0.001]. IKZF1 mutations mostly occurred in Ph+and Ph-like B-ALL, characterized by abnormal JAK-STAT pathway, and B-ALL with PAX5 translocation. Conclusions: Through the optimized bioinformatics analysis process, RNA-seq data can be used to classify and quantitatively analyze IKZF1 transcripts in B-ALL. Furthermore, the relative expression of mutant IKZF1 transcripts was found to cluster into two groups, and IKZF1 mutation was found often accompanied with PAX5 translocations.

[Trend analysis of the burden of ischemic heart disease in China, 1990 to 2015].

Objective: The objective of this study is to analyze the trend of burden of ischemic heart disease (IHD) in China between 1990 and 2015. Methods: Data were collected from the results of 2015 Global Burden of Disease Study. We arranged and analyzed the mortality and disability-adjusted life year (DALY) for IHD by sexes, ages and provinces (excluding Taiwan, China) in China between 1990 and 2015. The age-standardized rates were determined using the average world population age structure in the period of 2010-2035 as a reference, and the changes of the related indicators were calculated. Results: In 2015, IHD caused 1 461 thousand deaths, and its age-standardized death rate was 114.8 per 100 000. Number of DALYs from IHD were 25 765 thousand in 2015, with the age-standardized DALY rate at 1 760.2 per 100 000. From 1990 to 2015, the age-standardized death rate for IHD in China increased by 13.3% but age-standardized DALY rate decreased by 3.9%. Number of IHD DALYs among male (16 664 thousand) was higher than it among female (9 101 thousand) in China in 2015, and 83.5% of total DALYs from IHD occurred among people aged over 50 years old. Province with highest age-standardized death rate was Heilongjiang, with rate at 187.4 per 100 000 in 2015. Qinghai (54.0%) increased most and Macao (-52.3%) decreased most from 1990 to 2015. Province with highest age-standardized DALY rate was Xinjiang, with rate at 3 040.8 per 100 000 in 2015. Qinghai (33.2%) increased most while Macao (-59.0%) decreased most between 1990 and 2015. Conclusion: Burden of IHD in China increased remarkably from 1990 to 2015, especially among males and people aged over 50 years old. The differences among provinces were obvious.

Reactivity of patients with maintenance hemodialysis to erythropoietin in the treatment of renal anemia.

To explore the reactivity of patients with renal anemia (MHD) to erythropoietin (EPO) in maintenance hemodialysis (HD), 31 patients were enrolled in this study. According to the level of serum ferritin (SF), they were divided into two groups; one group received treatment using recombinant human erythropoietin (rHuEPO) and the other group was given iron sucrose. Taking terminal EPO dosage, terminal erythropoietin resistance index (ERI) and rate of change of ERI (ΔERII) as target indexes, the influence of SF level on dosage of EPO was evaluated after usage conditions of relevant substances in a 3-month period. The results revealed that differences of dialysis age, albumin (ALB), blood calcium, initial and terminal SF, variable quantity of hemoglobin (Hb), terminal EPO and ERI between two groups had statistical significance. Furthermore, SF level and terminal EPO (r = -0.37, P < 0. 05) as well as SF level and terminal ERI (r = - 0.39, P <0.05) were negatively correlated. Difference of terminal ERI between the two groups had statistical significance. It can therefore be summarized that supplementing an iron agent intravenously to maintain SF level between 500 ng/ml and 1200 ng/ml may improve reactivity of patients with MHD to EPO. In addition, rHuEPO therapy in treating anemia of patients with MHD has the same effect with intravenous drug delivery, less side effects and is easy to administer.

Effects of sodium ferrous chlorophyll treatment on anemia of hemodialysis patients and relevant biochemical parameters.

This study explores the effects of sodium ferrous chlorophyll treatment on the anemia of maintenance hemodialysis (MHD) patients, as well as the relevant biochemical parameters. We selected 72 patients who had received regular MHD treatment two or three times a week for more than 3 months in the Hospital of Traditional Chinese Medicine of Zhengzhou City of Henan Province from March 2014 to March 2016. They were equally divided into a treatment group and a control group. Haemoglobin (HB) and hematocrit (HCT) of the treatment group increased significantly after treatment (p < 0.01), but less in the control group (p < 0.05); Also serum ferritin (SF) and transferrin saturation (TAST) of the treatment group increased significantly after treatment (p < 0.01); SF of the control group also increased significantly (p < 0.01) and TAST of the control group increased (p < 0.05) but less than in the treatment group. No obvious changes of serum creatinine (SCR), blood urea nitrogen (BUN), C-reactive protein (CRP) and superoxide dismutase (SOD) were found in either groups after treatment (p>0.05). Albumin (ALB) dosage of the treatment group increased after treatment (p < 0.05) while hemopoietin (EPO) decreased significantly (p < 0.01). ALB and EPO of the control group had no obvious changes after treatment (p>0.05). ALB level of the treatment group increased more significantly than in the control group (p < 0.05), while EPO dosage decreased more significantly than in the control group (p <0.05). Therefore, the combination of conventional western medicine and sodium ferrous chlorophyll can effectively improve anemia conditions of MHD patients and their quality of life.

Development and validation of single nucleotide polymorphism markers in Odontobutis potamophila from transcriptomic sequencing.

Transcriptome sequencing technology has been applied in the development and discovery of single nucleotide polymorphism (SNP) markers in fish. In this study, a panel of 120 expressed sequence tag (EST)-derived SNPs was selected by several selection filters from the resultant EST library of Odontobutis potamophila using Illumina Sequencing. In total, 37 SNPs from 120 putative SNPs were considered as the true SNPs using Sanger sequencing. For each SNP locus of 30 individuals of one wild population of O. potamophila that was successfully calculated, the number of alleles per locus was 2 with an observed heterozygosity of 0.0000-0.9000 and an expected heterozygosity of 0.1000-0.5263. A total of 33 loci conformed to Hardy-Weinberg equilibrium (HWE), and 4 loci deviated from HWE after Bonferroni correction. These 33 SNP markers will benefit the studies of population genetic structure, population evolution analysis, and construction of a high-density linkage map of O. potamophila.

Molecular cloning and characterization of a proliferating cell nuclear antigen gene by chemically induced male sterility in wheat (Triticum aestivum L.).

Although a number of studies have shown that chemical hybridizing agents (CHAs) affect anther growth and regulate cell-cycle progression, little is known about the molecular and cellular mechanisms involved. Proliferating cell nuclear antigen (PCNA) is an essential factor in DNA replication, and in many other processes in eukaryotic cells. In this study, the open reading frame of TaPCNA, the PCNA in wheat (Triticum aestivum L.), was cloned by reverse transcription polymerase chain reaction (RT-PCR). Sequence analysis revealed that this gene was 792-bp long and encoded a protein with 234 amino acids. Alignment of the TaPCNA-predicted sequence revealed a high degree of identity with PCNAs from other plant species. A subcellular localization assay indicated that TaPCNA was localized in the nucleus. The TaPCNA was cloned into the prokaryotic expression plasmid pET32a, and the recombinant plasmid was transformed into BL21 (DE3). TaPCNA expression was induced by 0.5 mM isopropyl-beta-D-thiogalactopyranoside and verified using sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blot assays, which indicated that the fusion protein was successfully expressed. The gene involved in the G1-to-S transition, Histone H4, was downregulated by 1376- CIMS, which is a chemically induced male sterility line. However, a semi-quantitative RT-PCR revealed that TaPCNA expression was upregulated in 1376-CIMS. Our results suggest that CHAs (SQ-1) induce DNA damage in wheat anthers. DNA damage results in either the delay or arrest of cell-cycle progression, which affects anther development. This study will help to elucidate the mechanisms of SQ-1-induced male sterility.

Molecular cloning, characterization, and expression of vacuolar-type-H⁺-ATPase B1 (VHAB1) gene in the gill of Anguilla marmorata.

We explored the molecular mechanism of the regulation of vacuolar-type-H+-ATPase B1 (VHAB1) in elvers in the response to salinity. The full-length cDNA of VHAB1 in Anguilla marmorata (designated as AmVHAB1), which was 1741 base pairs (bp) in length, was found to encompass a 1512-bp open reading frame encoding a polypeptide with 503 amino acids (55.9 kDa), an 83-bp 5'-untranslated region, and a 146-bp 3'-untranslated region. The mRNA and protein expression levels of AmVHAB1 in the gill were evaluated at different time points (0, 1, 3, 6, 12, 24, 48, 72, and 96 h, and 15 days) during the exposure to various salinity levels (0, 10, and 25‰). The results indicated that the expression levels of AmVHAB1 mRNA in the gill significantly increased and reached the highest level at 1 h exposure in the brackish water (BW, 10‰) group and at 6 h exposure in the seawater (SW, 25‰) group. The salinity level affected the relative expression level of AmVHAB1 mRNA in the gill, which was increased by approximately 44-fold in the SW group when compared with that in fresh water. Immunoblotting analysis showed that VHA expression was significantly higher in the BW and SW groups, with the highest expression level was detected at 96 h exposure. We found that the AmVHAB1 gene in elvers from A. marmorata plays an important role in the adaptation to seawater.

Relationship between male sterility and ß-1,3-glucanase activity and callose deposition-related gene expression in wheat (Triticum aestivum L.).

In previous studies, we first isolated one different protein ß-1,3-glucanase using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry from normal wheat (Triticum aestivum L.) and chemical hybridization agent-induced male sterility (CIMS) wheat. In this experiment, ß-1,3-glucanase activity and the expression of a callose deposition-related gene, UDP-glucose phosphorylase (UGPase), were determinate in normal, CIMS, and genetic male sterility (GS) wheat. ß-1,3-glucanase activity was significantly different between the fertile and sterile lines during callose synthesis and degradation, but there was no difference between CIMS and GS wheat. The UGPase gene of callose deposition was highly expressed in the meiophase and sharply decreased in the tetrad stage. However, the expression of the UGPase gene was significantly different between the fertile and sterile lines. These data indicated that ß-1,3-glucanase activity and the expression of the UGPase gene play important roles in the male sterility of wheat. Consequently, pollen mother cells (PMCs) might degenerate at the early meiosis stage, and differences in UGPase gene expression and ß-1,3-glucanase activity might eventually result in complete pollen collapse. In addition, the critical period of anther abortion might be the meiosis stage to the tetrad stage rather than what we previously thought, the mononuclear period.

Value of C-arm computed tomography in radiofrequency ablation of small lung lesions.

This study aimed to explore the value of C-arm computed tomography (CT) applications in radiofrequency ablation (RFA) of small lung lesions. The puncture success rate, cumulative survival rate, tumor response rate, complications, and radiation dose during C-arm CT-guided RFA of 36 small lung lesions in 34 patients were analyzed. In 35 RFA procedures for 36 small lung lesions, the puncture success rate was 100%. There were 7 cases of complications, including 4 cases of pneumothorax (puncture suction or closed chest drainage was not required) and 3 cases of hemoptysis. The cumulative survival rate in the 34 patients after RFA was 100% at 6 months, 69.0% at 1 year, and 60.0% at 2 years. In assessments of 36 foci imaged during the follow-up period, the total response rates at 1 month, 3 months, and 6 months were 77.8% (28/36), 69.7% (23/33), and 61.3% (19/31), respectively. The mean cumulative dose and average effective dose during surgery were 120.1 ± 61.4 mGy and 3.5 ± 1.7 mSv, respectively. The application of C-arm CT to RFA of small lung lesions could provide abundant information to the surgeon and increase the lesion puncture success rate and is considered to be a promising image-guided technology.

Genetic polymorphisms in metabolic enzymes and susceptibility to anti-tuberculosis drug-induced hepatic injury.

We examined the relationships between N-transacetylase 2 (NAT2), cytochrome P450 (CYP) 2E1 enzyme, glutathione S-transferase M1, T1 (GSTM1/GSTT1) gene polymorphisms, and anti-tuberculosis drug-induced hepatic injury (ADIH). A one-to-one matched case-control study was carried out using clinical data. NAT2, CYP2E1, GSTM1, and GSTT1 polymorphisms were identified in 173 pairs of research subjects. Statistical analysis was performed to determine risk factors of ADIH. The results showed that low body mass index and alcohol consumption were risk factors of ADIH, with odds ratios of 6.852 and 3.203, respectively. The frequencies of NAT2 slow acetylator, CYP2E1 -1259G>C, -1019C>T wild-type, and the GSTM1 null genotype were higher in the case group than in the control group, with odds ratios of 2.260, 2.696, 4.714, and 2.440, respectively. GSTT1 was not found to be related to ADIH. Interactive analysis showed that NAT2 slow acetylator and the GSTM1 null genotype were mutually synergistic, while an antagonistic relationship was observed between the CYP2E1 wild-type genotype and the other 3 genetic types. The risks of hepatic injury were higher after anti-tuberculosis therapy in patients carrying the NAT2 slow acetylator, CYP2E1 -1259G>C, -1019C>T wild-type, and GSTM1 null genotype.

The progress and controversies regarding steroid use in acute spinal cord injury.

Acute spinal cord injury (SCI) is a devastating disease that causes immense physical and mental harm to the patient and the family, and society and requires a multidisciplinary approach to treatment. The study of acute SCI has a long history but is still emerging. As the mechanism and pathophysiology of acute SCI are continuously being studied and explored, the treatment of SCI has developed significantly. Steroids are thought to provide neuroprotection in patients with acute SCI by improving perfusion, reducing edema, modulating inflammatory cells, and inhibiting lipid peroxidation, leading to their widespread application in clinical medicine. The use of steroids for SCI is controversial because of limited clinical evidence. With the accumulation of evidence on the effectiveness of steroid treatment in improving neurological function and the evidence of severe side effects, a gradual change in the treatment of SCI with steroids has become inevitable. Most scholars have focused on the routine use of steroids because of the indefinite improvement in neurological function and the occurrence of severe adverse events. Therefore, this review aims to provide an overview of the mechanism, progress, and related controversies to comprehensively understand the value and future direction of steroid application in acute SCI.

Ultrasonography for confirmation of emergency department endotracheal tube placement: a meta-analysis.

OBJECTIVE: This meta-analysis aimed to summarize the evidence on the use of ultrasonography for confirming endotracheal tube placement in emergency departments. MATERIALS AND METHODS: We conducted electronic searches on PubMed, Embase, Web of Science, and Cochrane databases. All databases were searched from their inception until February 2023. We selected studies published in English that used ultrasonography to confirm endotracheal tube placement. Case reports, case series, retrospective studies, cadaveric studies, pediatric studies, animal studies, and conference abstracts were excluded. Two reviewers independently extracted and verified data. Forest plots, hierarchical summary receiver operating characteristic (HSROC) curves, and bivariate random-effects models were used to summarize the test performance characteristics. The Stata statistical software package and Meta-DiSc version 1.4 software were used for statistical analysis. RESULTS: A total of 1,772 intubations were analyzed. For the detection of endotracheal tube placement, the estimated pooled sensitivity and specificity were 0.98 (95% CI: 0.97-0.99) and 0.92 (95% CI 0.85-0.95), respectively. The pooled positive and negative likelihood ratios were 11.70 (95% CI: 6.49-21.07) and 0.02 (95% CI: 0.01-0.03), respectively. The diagnostic odds ratio of ultrasonography was 221.13, and the area under the HSROC curve revealed an appropriate accuracy of 0.99. CONCLUSIONS: Current evidence supports the use of ultrasonography as a worthwhile alternative for endotracheal tube identification for intubations performed in emergency departments. This method can be used in conjunction with capnography as a preliminary test before final confirmation with capnography.

Protein tyrosine phosphatase SHP2 regulates TGF-ß1 production in airway epithelia and asthmatic airway remodeling in mice.

BACKGROUND: Transforming growth factor (TGF)-ß1 produced in airway epithelia has been suggested as a contributor to the airway remodeling observed in asthma patients. The protein tyrosine phosphatase SHP2 is a demonstrable modulator of TGF-ß1 production and thus a potential regulator of airway remodeling. OBJECTIVES: To define the signal event by which SHP2 regulates asthmatic responses in airway epithelial cells by using a mouse model of experimental OVA-induced airway remodeling. METHODS: The airways of Shp2(flox/flox) mice were infected with recombinant adenovirus vectors expressing a Cre recombinase-green fluorescence protein (GFP) fusion protein as part of allergen provocation studies using mice sensitized with ovalbumin (OVA) and repeatedly challenged with OVA. Several endpoint pathologies were assessed, including airway hyper-responsiveness (AHR), lung inflammatory score, peribronchial collagen deposition, and α-smooth muscle actin (SMA) hyperplasia. In vitro studies using airway epithelial cells (BEAS-2B) were used to investigate the role of SHP2 in the regulation of pulmonary remodeling events, including the expression of collagen, α-SMA, and TGF-ß1. RESULTS: Chronic OVA challenges in wild-type mice resulted in airway remodeling and lung dysfunction (e.g., increased inflammatory scores, collagen deposition (fibrosis), smooth muscle hyperplasia, and a significant increase in AHR). These endpoint pathology metrics were each significantly attenuated by conditional shp2 gene knockdown in airway epithelia. In vitro studies using BEAS-2B cells also demonstrated that the level of TGF-ß1 production by these cells correlated with the extent of shp2 gene expression. CONCLUSIONS: SHP2 activities in airway epithelial cells appear to modulate TGF-ß1 production and, in turn, regulate allergic airway remodeling following allergen provocation. CLINICAL IMPLICATIONS: Our findings identify SHP2 as a previously underappreciated contributor to the airway remodeling and lung dysfunction associated with allergen challenge. As such, SHP2 represents a potentially novel therapeutic target for the treatment of asthmatics. CAPSULE SUMMARY: Airway epithelial protein tyrosine phosphatase SHP2 appears to modulate TGF-ß1 activities as part of one or more cellular pathways leading to regulating the airway remodeling and lung dysfunction occurring in mouse models of allergic respiratory inflammation.

Acquired factor XIII inhibitor: clinical features, treatment, fibrin structure and epitope determination.

Acquired factor XIII (FXIII) deficiency, arising from an autoantibody against factor XIII, is a rare bleeding disorder. This autoimmune disorder most commonly occurs in the elderly. Patients who develop such acquired FXIII inhibitors may present with catastrophic bleeding events and are hard to be diagnosed with the normal general coagulation tests. Though the disease is relatively rare, it is known to cause significant mortality. In this article we briefly describe a patient who presented with extensive bleeding and a normal activated partial thromboplastin time and prothrombin time (PT), but had an acquired inhibitor to FXIII; her primary disease was systemic lupus erythematosus (SLE). Also, we will focus on the clinical features, treatment modalities, fibrin structure and epitope identification for acquired factor XIII inhibitor with a review of the literature.

The effect of Nrf2 activators tBHQ and 4-octyl itaconate on the nucleus pulposus cell degeneration.

OBJECTIVE: The present study aimed to investigate the impact of two Nrf2 agonists, tBHQ and 4-Octyl Itaconate, on nucleus pulposus (NP) degeneration and explore the underlying mechanism. PATIENTS AND METHODS: We isolated the NP cells from the disc tissue of disc herniation patients. NP cells were pretreated with an adequate dose of tBHQ, Itaconate, or the mixture of them, and then subjected to the Lipopolysaccharides (LPS) stimulation to induce degeneration. Besides, the Nrf2 gene silenced NP cells were also used as a comparison. Moreover, the LPS-treated NP cells were also cultured in the mix of tBHQ and Itaconate to determine whether the agonists affected reverse degeneration. RESULTS: LPS treatment suppressed Nrf2 expression and induced the NP cell degeneration with a decrease of cell viability and collagen II expression, an increase of reactive oxygen species (ROS) production, inflammatory cytokine accumulation (IL-1ß, TNF-α), and apoptosis (Caspase3, Caspase8). However, tBHQ or Itaconate pretreated NP cells contained a higher level of Nrf2 protein and alleviated the negative effect caused by LPS, which was abolished with the silencing of Nrf2. Additionally, tBHQ showed a better ability to suppress ROS than Itaconate. Meanwhile, Itaconate inhibited a higher amount of IL-1ß and TNF-α than tBHQ. Interestingly, when NP cells were pretreated with both tBHQ and Itaconate, the result indicated an excellent anti-ROS and anti-inflammatory peculiarity. Furthermore, when NP cells suffered from LPS first and then treated with the agonist, the anti-ROS and anti-inflammatory effects remained. However, the cell viability, collagen II, and apoptotic degree were not improved. CONCLUSIONS: Both tBHQ and Itaconate effectively prevent NP cells from degeneration through anti-ROS and anti-inflammation, and the combined use of them may have better effects. But in comparison, their impact on reversing NP cell degeneration has yet to be proven.

The persistent impacts of polyester microfibers on soil bio-physical properties following thermal treatment.

Soilborne microplastics can persist for decades and their consequences are of growing concern. Therefore, it is important to explore the feasible approaches for eliminating microplastic effects on soil properties. Through an incubation experiment, we evaluate the effects of thermal treatment on physical properties, enzymatic activities and microbial communities in polyester-microfibers contaminated soils. The effects of polyester-microfiber levels (0%, 0.1%, 0.3% and 1.0% of soil dry weight) on soil properties were detected under not heated (PMF), heated (mPMF) and added with natural-organic-matters (OM) following heated (mPMF+OM) conditions. Our results showed that 1.0% mPMF soil had lower bulk density and higher mean weight diameter than 0% mPMF soil, akin to PMF soils. Meanwhile, great volumes of < 30 µm pores in 0.3% and 1.0% mPMF soils were observed than that in 0% mPMF soil. Additionally, the dose-effects of melted polyester-microfiber on soil enzymatic activities and bacterial communities were still observed following thermal treatment, even under the OM added condition. Furthermore, our results demonstrated that polyester microfibers influenced soil microbial communities and functioning via altering specific soil physical properties, regardless of thermal treatment or not. Results of this study should be useful to guide further develop viable methods for remediating soils contaminated with microplastics.

Polyester microfiber and natural organic matter impact microbial communities, carbon-degraded enzymes, and carbon accumulation in a clayey soil.

Microplastics can alter microbial communities and enzymatic activities in soils. However, the influences of microplastics on soil carbon cycling which driven by microbial communities remain largely unknown. In this study, we investigated the effects of polyester microfiber (PMF) and natural organic matter（OM）on soil microbial communities, carbon-degraded enzymes, and carbon accumulation through an incubation experiment. Our results showed that the addition of PMF increased the activities of soil cellulase and laccase but did not impact soil bacterial and fungal communities too much. However, the addition of OM largely altered soil microbial communities and the activities of carbon-degraded enzymes, then mitigated the PMF effects on the activities of soil cellulase and laccase. On the other hand, greater alpha diversity of bacterial community attached on PMF was observed than those in the surrounding soils. The interaction of PMF and OM increased the richness of bacterial community in soils and on PMF. More importantly, we observed that the accumulation of natural organic carbon in soils reduced with increasing PMF. Thus, our results provide valuable insights into the effects of microplastics on soil organic carbon dynamics and microbial communities, and further work is required to clarify the biochemical processes at the surface of microplastics.

Down-regulation of mitochondrial ATPase by hypermethylation mechanism in chronic myeloid leukemia is associated with multidrug resistance.

BACKGROUND: To identify novel proteins involved in multidrug resistance in chronic myeloid leukemia (CML). MATERIALS AND METHODS: Comparative proteomics was used to screen multidrug resistance-related proteins from K562 and K562/A02; the differently expressed proteins were further confirmed by western blot and real-time PCR. short hairpin RNA (shRNA) assay was applied to determine the relationship between candidate protein and adriamycin resistance. Bisulfite sequencing was carried out to assess methylation status of candidate multidrug resistance-related gene promoter. K562/A02 was treated with 5-azacytidine or trichostatin A (TSA); multidrug resistance phenotype and corresponding protein or gene changes were detected. RESULTS: Seventeen proteins with altered abundances of more than twofold were detected, among which mitochondrial ATPase in K562/A02 was significantly down-regulated. Suppressing mitochondrial ATPase by shRNA could enhance adriamycin resistance and antiapoptosis activity of K562. The promoter hypermethylation in mitochondrial ATPase was found to be attributed to the adriamycin-resistant phenotype of both K562/A02 (methylated frequency 18.18%) and CML primary cells in accelerated phase (methylated frequency 7.95%) or blast crisis (methylated frequency 26.59%). Inhibition of hypermethylation increased adriamycin sensitivity of K562/A02. A synergistic effect on reversing adriamycin-resistant phenotype was obtained when 5-azacytidine was combined with TSA. CONCLUSION: Down-regulation of mitochondrial ATPase can lead to adriamycin resistance in CML and the mechanism is associated with DNA methylation regulation.

Variations in aggregate-associated organic carbon and polyester microfibers resulting from polyester microfibers addition in a clayey soil.

Organic carbon is an essential element for sustainable soil management. While the effects of microplastics on soil physical and biological properties are presenting, it remains unclear whether the organic carbon dynamics of soil are altered by increased microplastic accumulation. The objectives of this study were to evaluate the influences of different polyester microfiber (PMF 0, 0.1% and 0.3% of soil dry weight) and organic material (OM 0, 1%, 2% and 3% of soil dry weight) addition levels on soil organic carbon and to determine the PMF distribution in aggregates from a pot experiment. After 75 days of incubation under 6 wet-dry cycles, the concentrations of soil total organic carbon did not differ significantly between the PMF (9.7 ± 6.6 g kg-1) and control (9.7 ± 6.9 g kg-1) treatments. However, PMF addition significantly reduced the organic carbon concentration in the large (>2 mm) macro-aggregates compared to the control treatment (10.6 ± 4.8 g kg-1 vs. 11.7 ± 4.4 g kg-1), but the results were opposite in the small (2-0.25 mm)macro-aggregates (10.2 ± 4.9 g kg-1 vs. 8.4 ± 3.8 g kg-1). In this study, less than 30% of added PMFs were incorporated into soil aggregates. In addition, the abundance and average length of aggregate-associated PMF in the large (2210 ± 180 particles per g aggregate and 2.08 ± 0.17 mm) and small (1820 ± 150 particles per g aggregate and 1.68 ± 0.11 mm) macro-aggregates were significantly greater than those in the micro-aggregates (1010 ± 70 particles per g aggregate and 0.72 ± 0.05 mm). Our results demonstrate that the distribution of organic carbon in soil macro-aggregates is affected by PMFs addition. Thus, we propose that the behavior of microplastics inside soil aggregates should be further explored to clarify their effects on the physical protection of soil organic carbon.