Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion.

Bromodomain-containing protein 4 (BRD4), the major component of bromodomain and extra-terminal domain (BET) protein family, has important functions in early embryonic development and cancer development. However, the posttranslational modification of BRD4 is not well understood. Multiple approaches were used to explore the mechanism of PRMT1-mediated BRD4 methylation and to determine the biological functions of BRD4 and PRMT1 in ovarian cancer. Here we report that BRD4 is asymmetrically methylated at R179/181/183 by PRMT1, which is antagonized by the Jumonji-family demethylase, JMJD6. PRMT1 is overexpressed in ovarian cancer tissue and is a potential marker for poor prognosis in ovarian cancer patients. Silencing of PRMT1 inhibited ovarian cancer proliferation, migration, and invasion in vivo and in vitro. PRMT1-mediated BRD4 methylation was found to promote BRD4 phosphorylation. Compared to BRD4 wild-type (WT) cells, BRD4 R179/181/183K mutant-expressing cells showed reduced ovarian cancer metastasis. BRD4 arginine methylation is also associated with TGF-ß signaling. Our results indicate that arginine methylation of BRD4 by PRMT1 is involved in ovarian cancer tumorigenesis. Targeting PRMT1-mediated arginine methylation may provide a novel diagnostic target and an effective therapeutic strategy for ovarian cancer treatment.

Biomimetic redox-responsive smart coatings with resistance-release functions for reverse osmosis membranes.

Membrane fouling induces catastrophic loss of separation performance and seriously restricts the applications of reverse osmosis (RO) membranes. Inspired by the mussel structure, polydopamine (PDA) and cystamine molecules (CA) with excellent anti-fouling properties were used to prepare accessible, biocompatible, and redox-responsive coatings for RO membranes. The PDA/CA-coated RO membranes exhibit a superior water flux of 65 L m-2 h-1 with a favourable NaCl rejection exceeding 99%. The water permeability through the PDA/CA-coated membrane is much higher than that of most membranes with similar rejection rates. Due to the formed protective hydration layers by PDA/CA coatings, anti-fouling properties against proteins, polysaccharides and surfactants were evaluated separately, and ultralow fouling properties were demonstrated. Moreover, the disulfide linkages in CA molecules can cleave in a reducing environment, yielding the degradation of PDA/CA coatings, thereby removing the foulants deposited on the coatings. The degradation endows the coated membranes with satisfying longtime anti-fouling properties, where the flux recovery reaches up to 90%. The construction of redox-responsive smart coatings not only provided a promising route to alleviate membrane fouling but can also be upscaled for use in numerous practical applications like sensors, medical devices, and drug delivery.

Design and synthesis of fascaplysin derivatives as inhibitors of FtsZ with potent antibacterial activity and mechanistic study.

The increase in antibiotic resistance has made it particularly urgent to develop new antibiotics with novel antibacterial mechanisms. Inhibition of bacterial cell division by disrupting filamentous temperature-sensitive mutant Z (FtsZ) function is an effective and promising approach. A series of novel fascaplysin derivatives with tunable hydrophobicity were designed and synthesized here. The in vitro bioactivity assessment revealed that these compounds could inhibit the tested Gram-positive bacteria including methicillin-resistant S. aureus (MRSA) (MIC = 0.049-25 µg/mL), B. subtilis (MIC = 0.024-12.5 µg/mL) and S. pneumoniae (MIC = 0.049-50 µg/mL). Among them, compounds B3 (MIC = 0.098 µg/mL), B6 (MIC = 0.098 µg/mL), B8 (MIC = 0.049 µg/mL) and B16 (MIC = 0.098 µg/mL) showed the best bactericidal activities against MRSA and no significant tendency to trigger bacterial resistance as well as rapid bactericidal properties. The cell surface integrity of bacteria was significantly disrupted by hydrophobic tails of fascaplysin derivatives. Further studies revealed that these highly active amphiphilic compounds showed low hemolytic activity and cytotoxicity to mammalian cells. Preliminary mechanistic exploration suggests that B3, B6, B8 and B16 are potent FtsZ inhibitors to promote FtsZ polymerization and inhibit GTPase activity of FtsZ, leading to the death of bacterial cells by inhibiting bacterial division. Molecular docking simulations and structure-activity relationship (SAR) study reveal that appropriate increase in the hydrophobicity of fascaplysin derivatives and the addition of additional hydrogen bonds facilitated their binding to FtsZ proteins. These amphiphilic fascaplysin derivatives could serve as a novel class of FtsZ inhibitors, which not only gives new prospects for the application of compounds containing this skeleton but also provides new ideas for the discovery of new antibiotics.

PRAME Promotes Cervical Cancer Proliferation and Migration via Wnt/ß-Catenin Pathway Regulation.

A significant burden is placed on the lives of females due to cervical cancer, which is currently the leading cause of cancer death among women. Preferentially expressed antigen in melanoma (PRAME) belongs to the CTA gene family and was found to be abnormally expressed among different types of cancers. Our previous research also indicated that PRAME was highly expressed in cervical cancer compared with normal tissues. However, the roles and detailed mechanisms of PRAME have not been explored in cervical cancer. In the present study, the expression of PRAME in cervical tissues and cells was detected by immunohistochemistry (IHC), qRT-PCR, and Western blotting. Additionally, CCK-8, BrdU, scratch, transwell, and flow cytometry assays were conducted to explore the function of PRAME in regulating the malignant biological behaviors of cervical cancer cells. Nude mice were used to confirm the role of PRAME in tumor growth in vivo. Furthermore, the Wnt inhibitor MSAB was used to verify the role of PRAME in regulating the Wnt/ß-catenin pathway both in vitro and in vivo. The results of IHC, qRT-PCR, and Western blotting showed that PRAME was highly expressed in cervical cancer tissues and cells. PRAME knockdown attenuated cell growth, migration, and invasion; induced G0/G1 arrest; and increased cell apoptosis in C33A and SiHa cells through Wnt/ß-catenin signaling regulation. However, the upregulation of PRAME exhibited the opposite effects accordingly, which could be partly reversed via MSAB treatment. The growth rate of xenograft tumors was enhanced when PRAME was overexpressed via Wnt/ß-catenin signaling activation. Taken together, PRAME is associated with cervical cancer occurrence and progression mediated by Wnt/ß-catenin signaling, suggesting that PRAME might be a factor in manipulating cervical carcinogenesis and a potential therapeutic target.

DHODH Inhibition Exerts Synergistic Therapeutic Effect with Cisplatin to Induce Ferroptosis in Cervical Cancer through Regulating mTOR Pathway.

Ferroptosis exhibits a potent antitumor effect and dihydroorotate dehydrogenase (DHODH) has recently been identified as a novel ferroptosis defender. However, the role of DHODH inhibition in cervical cancer cells is unclear, particularly in synergy with cisplatin via ferroptosis. Herein, shRNA and brequinar were used to knock down DHODH and directly inhibit DHODH, respectively. Immunohistochemistry and Western blotting assays were performed to measure the expression of proteins. CCK-8 and colony formation assays were employed to assess the cell viability and proliferation. Ferroptosis was monitored through flow cytometry, the malondialdehyde assay kit and JC-1 staining analyses. The nude mouse xenograft model was generated to examine the effect of combination of DHODH inhibition and cisplatin on tumor growth in vivo. The expression of DHODH was increased in cervical cancer tissues. DHODH inhibition inhibited the proliferation and promoted the ferroptosis in cervical cancer cells. A combination of DHODH inhibition and cisplatin synergistically induced both in vitro and in vivo ferroptosis and downregulated the ferroptosis defender mTOR pathway. Therefore, the combination of DHODH inhibition and cisplatin exhibits synergistic effects on ferroptosis induction via inhibiting the mTOR pathway could provide a promising way for cervical cancer therapy.

A hydrophobic Cu/Cu2O sheet catalyst for selective electroreduction of CO to ethanol.

Electrocatalytic reduction of carbon monoxide into fuels or chemicals with two or more carbons is very attractive due to their high energy density and economic value. Herein we demonstrate the synthesis of a hydrophobic Cu/Cu2O sheet catalyst with hydrophobic n-butylamine layer and its application in CO electroreduction. The CO reduction on this catalyst produces two or more carbon products with a Faradaic efficiency of 93.5% and partial current density of 151 mA cm-2 at the potential of -0.70 V versus a reversible hydrogen electrode. A Faradaic efficiency of 68.8% and partial current density of 111 mA cm-2 for ethanol were reached, which is very high in comparison to all previous reports of CO2/CO electroreduction with a total current density higher than 10 mA cm-2. The as-prepared catalyst also showed impressive stability that the activity and selectivity for two or more carbon products could remain even after 100 operating hours. This work opens a way for efficient electrocatalytic conversion of CO2/CO to liquid fuels.

NSCKL: Normalized Spectral Clustering With Kernel-Based Learning for Semisupervised Hyperspectral Image Classification.

Spatial-spectral classification (SSC) has become a trend for hyperspectral image (HSI) classification. However, most SSC methods mainly consider local information, so that some correlations may not be effectively discovered when they appear in regions that are not contiguous. Although many SSC methods can acquire spatial-contextual characteristics via spatial filtering, they lack the ability to consider correlations in non-Euclidean spaces. To address the aforementioned issues, we develop a new semisupervised HSI classification approach based on normalized spectral clustering with kernel-based learning (NSCKL), which can aggregate local-to-global correlations to achieve a distinguishable embedding to improve HSI classification performance. In this work, we propose a normalized spectral clustering (NSC) scheme that can learn new features under a manifold assumption. Specifically, we first design a kernel-based iterative filter (KIF) to establish vertices of the undirected graph, aiming to assign initial connections to the nodes associated with pixels. The NSC first gathers local correlations in the Euclidean space and then captures global correlations in the manifold. Even though homogeneous pixels are distributed in noncontiguous regions, our NSC can still aggregate correlations to generate new (clustered) features. Finally, the clustered features and a kernel-based extreme learning machine (KELM) are employed to achieve the semisupervised classification. The effectiveness of our NSCKL is evaluated by using several HSIs. When compared with other state-of-the-art (SOTA) classification approaches, our newly proposed NSCKL demonstrates very competitive performance. The codes will be available at https://github.com/yuanchaosu/TCYB-nsckl.

Predictive Classification System for Low Back Pain Based on Unsupervised Clustering.

STUDY DESIGN: Retrospective study. OBJECTIVE: Lumbar magnetic resonance imaging (MRI) findings are believed to be associated with low back pain (LBP). This study sought to develop a new predictive classification system for low back pain. METHOD: Normal subjects with repeated lumbar MRI scans were retrospectively enrolled. A new classification system, based on the radiological features on MRI, was developed using an unsupervised clustering method. RESULTS: One hundred and fifty-nine subjects were included. Three distinguishable clusters were identified with unsupervised clustering that were significantly correlated with LBP (P = .017). The incidence of LBP was highest in cluster 3 (57.14%), nearly twice the incidence in cluster 1 (30.11%). There were obvious differences in the sagittal parameters among the 3 clusters. Cluster 3 had the smallest intervertebral height. Based on follow-up findings, 27% of subjects changed clusters. More subjects changed from cluster 1 to clusters 2 or 3 (14.5%) than changed from cluster 2 or cluster 3 to cluster 1 (5%). Participation in sport was more frequent in subjects who changed from cluster 3 to cluster 1. CONCLUSION: Using an unsupervised clustering method, we developed a new classification system comprising 3 clusters, which were significantly correlated with LBP. The prediction of LBP is independent of age and better than that based on individual sagittal parameters derived from MRI. A change in cluster during follow-up may partially predict lumbar degeneration. This study provides a new system for the prediction of LBP that should be useful for its diagnosis and treatment.

δ-Catenin Requirement in Keratinocyte Proliferation and DNA Repair Identifies a Therapeutic Target for Photoaging.

Skin photoaging is a complicated pathological process and is mainly due to UV irradiation, especially UVB irradiation. Damage induction by UVB is a complex process, involving intricate molecular mechanisms. The formation of bulky photoproducts in the DNA globally affects transcription and splicing and results in the dysfunction of keratinocytes. In this study, we show that δ-catenin is predominantly distributed in keratinocytes of the skin epidermis and functionally accelerates cell proliferation and DNA repair. Ex vivo protein profiling reveals that δ-catenin upregulates the phosphorylation of RSK2Ser-227 by enhancing the interaction between PDK1 and RSK2 and thereby induces the nuclear accumulation of YB1 to promote proliferation and DNA repair. Moreover, δ-catenin overexpression induces in vivo keratinocyte proliferation and DNA repair in UVB-irradiated mouse skin. Notably, acidic fibroblast GF/FGFR1 is identified as one of the key upstream signalings of δ-catenin by inducing δ-catenin stabilization. The involvement of δ-catenin in keratinocyte proliferation and DNA repair may suggest δ-catenin as a target for the treatment of UVB damage.

Association of Vitamin D Anabolism-Related Gene Polymorphisms and Susceptibility to Uterine Leiomyomas.

Background: Uterine leiomyomas (ULs) is the most common gynecological benign tumor in women. Our previous study showed that the phenomenon of vitamin D deficiency existed in patients with ULs. However, the association of vitamin D anabolism-related gene polymorphisms and susceptibility to ULs was unclear. Methods: Vitamin D anabolism-related gene polymorphisms in 110 patients with ULs and 110 healthy controls were detected by sequencing and the differences of the 92 SNPs were analyzed in the two groups via chi-square test. To verify the association between the significantly different SNPs and the risk of ULs, the SNPs were genotyped in another 340 patients and 340 healthy controls. Additionally, an unconditional logistic regression model was conducted to calculate the odds ratio (OR) of ULs occurrence and the 95% confidence interval (CI), adjusting for age and BMI. Findings: In sequencing samples, there were differences in DHCR7 rs1044482 C > T (p = 0.008) and NADSYN1 rs2276360 G > C (p = 0.025) between patients with ULs and healthy controls. DHCR7 rs1044482 was related to the susceptibility to ULs in validation samples (heterogeneous: adjusted OR = 1.967, p = 0.002; homogenous: adjusted OR = 2.494, p = 0.002; additive: adjusted OR = 1.485, p < 0.041; and dominant: adjusted OR = 2.084, p < 0.001). Stratified analysis further showed that the DHCR7 rs1044482 polymorphisms were associated with ULs risks in women over 40 and with 18.5-25.0 BMI. In contrast to the wild-type CG haplotype vectors, individuals with TC haplotypes had a higher risk of developing ULs. Interpretation: The vitamin D anabolism-related gene DHCR7 rs1044482 C > T polymorphism was a risk factor of ULs, especially in patients over 40 with 18.5-25.0 BMI, while the relationship between NADSYN1 rs2276360 and ULs risk was not clear.

Ribosomal S6 Protein Kinase 2 Aggravates the Process of Systemic Scleroderma.

Systemic sclerosis is a complex process of pathogenesis, and the contributions of inherited genes, infections, and chemicals remain largely unknown. In this study, we showed that p90 ribosomal S6 protein kinase 2 (RSK2) was selectively upregulated in fibrotic skin and fibroblasts treated with the profibrotic cytokine TGF-ß. Moreover, knockout of Rsk2 specifically in skin fibroblasts or pharmacological inhibition of RSK2 attenuated skin fibrosis in a mouse model. Mechanistically, RSK2 directly interacted with glycogen synthase kinase 3ß in vivo and in vitro and thereby induced phosphorylation of glycogen synthase kinase 3ß at Ser9 to inhibit ubiquitination and degradation of GLI1, which promoted fibroblast differentiation and skin fibrosis. Consequently, RSK2 plays an important role in the dermal skin of systemic sclerosis. These findings provided a potential therapeutic target for systemic sclerosis.

Eco-friendly chitosan@silver/plant fiber membranes for masks with thermal comfortability and self-sterilization.

The surgical masks have been essential consumables for public in the COVID-19 pandemic. However, long-time wearing masks will make wearers feel uncomfortable and massive discarded non-biodegradable masks lead to a heavy burden on our environment. In this paper, we adopt degradable chitosan@silver (CS@Ag) core-shell fibers and plant fibers to prepare an eco-friendly mask with excellent thermal comfort, self-sterilization, and antiviral effects. The thermal network of CS@Ag core-shell fibers highly improves the in-plane thermal conductivity of masks, which is 4.45 times higher than that of commercial masks. Because of the electrical conductivity of Ag, the fabricated mask can be electrically heated to warm the wearer in a cold environment and disinfect COVID-19 facilely at room temperature. Meanwhile, the in-situ reduced silver nanoparticles (AgNPs) endow the mask with superior antibacterial properties. Therefore, this mask shows a great potential to address the urgent need for a thermally comfortable, antibacterial, antiviral, and eco-friendly mask. Supplementary Information: The online version contains supplementary material available at 10.1007/s10570-022-04582-x.

[The Factors Affecting Relapse in Pediatric B-cell Acute Lymphoblastic Leukemia Patients without Prognostic Fusion Genes Following Up for 10 years].

OBJECTIVE: To analyze the efficacy of children with B-cell acute lymphoblastic leukemia (B-ALL) without prognostic fusion genes treated by CCLG-ALL 2008, and investigate the related factors affecting the recurrence of the patients. METHODS: B-ALL patients without prognostic fusion genes treated by the protocol of CCLG-ALL 2008 in our hospital from March 2008 to December 2012 were retrospectively analyzed. Follow-up time was ended in August 31, 2019. The median follow-up time was 92 months (range 0-136 months). Kaplan-Meier was used to detect the RFS, and COX multivariate regression analysis was employed to identify the independent factors affecting the recurrence of the patients. RESULTS: There were 140 males and 99 females enrolled in this study. The ratio of male to female was 1.41∶1. The median age was 4.4 years old and the median number of WBC at initial stage was 4.98×109/L. There were 77 cases relapsed during the observation while 162 without relapsed, 16 cases lost to follow-up and 72 cases died. The recurrence and mortality rate was 32.22% and 30.1%, respectively, in which 45 cases died of recurrence (62.5% of the total deaths). Univariate analysis showed that the age≥6 years old, WBC >100×109/L, the bone marrow blasts on day 15≥25%, the bone marrow minimal residual disease (MRD) at week 12 >10-4, and the higher risk were the main factors affecting the recurrence of the patients (P<0.05). Multivariate COX regression analysis showed that age≥6 years old, WBC >100×109/L, bone marrow MRD >10-4 at the 12th week were the independent risk factors affecting recurrence of the patients. CONCLUSION: Age, initial WBC, and bone marrow MRD at the 12th week were correlated with recurrence in children with B-ALL without prognostic fusion genes, which can be used as prognostic indices of recurrence risk in clinical.

Phosphorylation of α-CateninS641 Suppresses the NF-κB Pathway in Fibroblasts to Activate Skin Wound Repair.

Skin wound healing is a complex process involving intricate molecular mechanisms that remain unknown. Restoration of homeostasis after wounding requires the remodeling function of fibroblasts. In this study, we show that phosphorylation of α-cateninS641 was upregulated in fibroblasts during wounding, which accelerated their proliferation and migration to restore the skin barrier. At the wound edge, phosphorylated α-cateninS641 stabilized IκBα and thereby impaired the expression of NF-κB target genes to promote proliferation and migration of fibroblasts. Mechanically, phosphorylated α-cateninS641 blocked K48-linked polyubiquitination and proteasomal degradation of IκBα. Moreover, we also showed that EGF/EGFR/CK2α functioned as key upstream signaling of α-catenin by phosphorylating α-catenin at S641. Wound repair was significantly disrupted in the skin of mice in which α-catenin phosphorylation and CK2α kinase activity were perturbed in fibroblasts. These findings provide insights into the molecular control of fibroblast proliferation and migration in response to wounding and identify potential targets for the treatment of defective wound repair.

Temperature-adjustable F-carbon nanofiber/carbon fiber nanocomposite fibrous masks with excellent comfortability and anti-pathogen functionality.

Wearing surgical masks remains the most effective protective measure against COVID-19 before mass vaccination, but insufficient comfortability and low antibacterial/antiviral activities accelerate the replacement frequency of surgical masks, resulting in large amounts of medical waste. To solve this problem, we report new nanofiber membrane masks with outstanding comfortability and anti-pathogen functionality prepared using fluorinated carbon nanofibers/carbon fiber (F-CNFs/CF). This was used to replace commercial polypropylene (PP) nonwovens as the core layer of face masks. The through-plane and in-plane thermal conductivity of commercial PP nonwovens were only 0.12 and 0.20 W/m K, but the F-CNFs/CF nanofiber membranes reached 0.62 and 5.23 W/m K, which represent enhancements of 380% and 2523%, respectively. The surface temperature of the PP surgical masks was 23.9 ℃ when the wearing time was 15 min, while the F-CNFs/CF nanocomposite fibrous masks reached 27.3 ℃, displaying stronger heat dissipation. Moreover, the F-CNFs/CF nanofiber membranes displayed excellent electrical conductivity and produced a high-temperature layer that killed viruses and bacteria in the masks. The surface temperature of the F-CNFs/CF nanocomposite fibrous masks reached 69.2 ℃ after being connected to a portable power source for 60 s. Their antibacterial rates were 97.9% and 98.6% against E. coli and S. aureus, respectively, after being connected to a portable power source for 30 min.

Significant value of XRCC2 and XRCC9 expression in the prognosis of human ovarian carcinoma.

Background: The x-ray repair cross-complementing (XRCC) family is essential in DNA repair processes. The predictive roles of XRCCs remain unclear in ovarian carcinomas. Therefore, detecting the relationship between XRCCs expression and ovarian carcinomas prognosis is increasingly pivotal. Methods: Using the "Kaplan-Meier (KM) plotter" database, progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the prognosis of XRCCs mRNA expression in ovarian carcinoma patients with clinical outcomes. Then, mRNA level and protein levels of XRCCs were assessed in normal ovarian cells and ovarian carcinoma cell lines by real-time qPCR, Western blotting and immunofluorescence analysis. Additionally, expression of the XRCCs protein in tissues from ovarian carcinomas and normal ovary was identified by immunohistochemical staining. Results: Higher mRNA levels of XRCC2 and XRCC9 predicted longer PFS and OS in all women with ovarian malignance, while elevated XRCC4 mRNA levels were linked to poor PFS and OS in all ovarian cancer patients. Elevated mRNA of XRCC2 was also correlated with better PFS in patients with serous ovarian carcinomas, and better PFS and OS in grade III and stage III+IV ovarian carcinomas patients. What's more, highly expressed levels of XRCC9 mRNA were also linked to favorable PFS and OS in patients with serous, grade III and stage III+IV ovarian carcinomas. Nevertheless, elevated mRNA expression of XRCC4 was linked to worse PFS and OS for patients with serous, grade III as well as all stages of ovarian malignance. Additionally, when compared to ovarian carcinoma cell lines, elevated mRNA and protein levels of XRCC2 and XRCC9 were detected in normal ovarian cells. Consistently, higher staining of XRCC2 and XRCC9 was also detected in normal ovarian cells than that in ovarian cancer cells. Then, higher staining levels of XRCC2 and XRCC9 were discovered in healthy control tissues than that in ovarian carcinoma tissues. Meanwhile, XRCC4 was identified to be overexpressed in tissues of ovarian malignance as compared to normal control tissues. However, XRCC4 mRNA and protein levels were lower in ovarian cancer cells than that in normal cell line. Conclusion: Elevated XRCC2 and XRCC9 expression levels were observed in normal ovarian cells and tissues than that in ovarian malignance cells and tissues, and exhibited better prognostic value especially in patients with serous, poor differentiated and late stage, suggesting that XRCC2 and XRCC9 may be potent prognostic markers in ovarian cancer patients and can guide personalized surveillance for ovarian malignance.

[The Factors Related to Treatment Failure in Children with Acute Lymphoblastic Leukemia].

OBJECTIVE: To analyze the efficacy of CCLG-ALL-2008 protocol and the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL). METHODS: The clinical data of 400 children newly-diagnosed ALL in Children's Hospital of Soochow University from March 1, 2008 to December 31, 2012 was retrospectively analyzed. All the children accepted CCLG-ALL-2008 protocol, and were followed-up until October 2019. The dates of relapse, death and causes of death were recorded. Treatment failure was defined as relapse, non-relapse death, and secondary tumor. RESULTS: Following-up for 10 years, there were 152 cases relapse or non-relapse death, the treatment failure rate was 38%, including 122 relapse (80.3%), 30 non-relapse deaths (19.7%) which included 7 cases (4 cases died of infection and 3 cases died of bleeding) died of treatment (23.3% of non-relapse deaths), 8 cases died of minimal residual disease (MRD) continuous positive (26.7% of non-relapse deaths) and 15 cases died of financial burden (50% of non-relapse deaths). According to the relapse stage, 37 cases (30%) in very early stage, 38 cases (31%) in early stage, and 47 cases (39%) in late stage, while according to the relapse site, 107 cases relapsed in bone marrow, 3 cases in testis, 3 cases in central nervous system (CNS), 5 cases in bone marrow plus testis and 4 cases in bone marrow plus CNS. Bone marrow relapse was the main cause of death in 89 cases, followed by nervous system. Initially diagnosed WBC count (≥50×109/L), T-cell immunophenotype, and MRD-positive at week 12 were the independent risk prognostic factors for relapse in children with ALL, while age (≥10 years), initially diagnosed WBC count (≥50×109/L), M3 bone marrow on day 15, and MRD-positive at week 12 were the independent risk factors due to treatment failure. No secondary tumors were found during the follow-up for 10 years. CONCLUSION: Relapse is the main cause of treatment failure in children with ALL. The initially diagnosed WBC count, immunophenotype and MRD at week 12 were the independent prognostic factors for relapse of the patients. Financial burden accounts for a large proportion of non-relapse death.

Highly thermally conductive and eco-friendly OH-h-BN/chitosan nanocomposites by constructing a honeycomb thermal network.

More than 110,000,000 tons of mismanaged plastics were to be produced in 2020. Polymers are favored in the preparation of thermally conductive materials due to their excellent comprehensive properties. However, most polymers fabricated for thermally conductive materials are difficult to degrade in the natural environment. To alleviate the increasingly severe environmental problems, we reported a novel eco-friendly material with high thermal conductivity, which was composited of chitosan microspheres (CSM) and hydroxyl-functionalized hexagonal boron nitride (OH-h-BN) nanoplatelets. Utilizing their significant difference in scales, the OH-h-BN nanoplatelets were arranged between each CSM. Their overall structure was similar to the honeycomb: CSM were honeycomb cores, and OH-h-BN nanoplatelets were honeycomb network. The routine-structure OH-h-BN/CS nanocomposites were only 0.94 ± 0.02 W·m-1·K-1 at 50 wt% in thermal conductivity. However, the OH-h-BN/CSM nanocomposites with honeycomb structure can reach 5.66 ± 0.32 W·m-1·K-1 in the same loading, for enhancement of 502% and 1914% than OH-h-BN/CS nanocomposites and pure CS, respectively.

Towards bio-upcycling of polyethylene terephthalate.

Over 359 million tons of plastics were produced worldwide in 2018, with significant growth expected in the near future, resulting in the global challenge of end-of-life management. The recent identification of enzymes that degrade plastics previously considered non-biodegradable opens up opportunities to steer the plastic recycling industry into the realm of biotechnology. Here, the sequential conversion of post-consumer polyethylene terephthalate (PET) into two types of bioplastics is presented: a medium chain-length polyhydroxyalkanoate (PHA) and a novel bio-based poly(amide urethane) (bio-PU). PET films are hydrolyzed by a thermostable polyester hydrolase yielding highly pure terephthalate and ethylene glycol. The obtained hydrolysate is used directly as a feedstock for a terephthalate-degrading Pseudomonas umsongensis GO16, also evolved to efficiently metabolize ethylene glycol, to produce PHA. The strain is further modified to secrete hydroxyalkanoyloxy-alkanoates (HAAs), which are used as monomers for the chemo-catalytic synthesis of bio-PU. In short, a novel value-chain for PET upcycling is shown that circumvents the costly purification of PET monomers, adding technological flexibility to the global challenge of end-of-life management of plastics.