Clonal evolution dissection reveals that a high MSI2 level promotes chemoresistance in T-cell acute lymphoblastic leukemia.

ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer with resistant clonal propagation in recurrence. We performed high-throughput droplet-based 5' single-cell RNA with paired T-cell receptor (TCR) sequencing of paired diagnosis-relapse (Dx_Rel) T-ALL samples to dissect the clonal diversities. Two leukemic evolutionary patterns, "clonal shift" and "clonal drift" were unveiled. Targeted single-cell DNA sequencing of paired Dx_Rel T-ALL samples further corroborated the existence of the 2 contrasting clonal evolution patterns, revealing that dynamic transcriptional variation might cause the mutationally static clones to evolve chemotherapy resistance. Analysis of commonly enriched drifted gene signatures showed expression of the RNA-binding protein MSI2 was significantly upregulated in the persistent TCR clonotypes at relapse. Integrated in vitro and in vivo functional studies suggested that MSI2 contributed to the proliferation of T-ALL and promoted chemotherapy resistance through the posttranscriptional regulation of MYC, pinpointing MSI2 as an informative biomarker and novel therapeutic target in T-ALL.

Decitabine-containing conditioning improved outcomes for children with higher-risk myelodysplastic syndrome undergoing allogeneic hematopoietic stem cell transplantation.

Myelodysplastic syndrome (MDS) is a rare clonal hematopoietic disorder in children. The risk stratification system and treatment strategy for adults are unfit for children. The role of hypomethylating agents (HMAs) in higher-risk childhood MDS has not been identified. This study aimed to investigate the outcomes of hematopoietic stem cell transplantation (HSCT) in children with higher-risk MDS at one single center. A retrospective study was conducted in children with higher-risk MDS undergoing HSCT between September 2019 and March 2023 at Blood Diseases Hospital CAMS. The clinical characteristics and transplantation information were reviewed and analyzed. A total of 27 patients were analyzed, including 11 with MDS with excess blasts (MDS-EB), 14 with MDS-EB in transformation (MDS-EBt) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 2 with therapy-related MDS/AML (t-MDS/AML). Eight patients harbored monosomy 7. Before transplantation, induction therapy was administered to 25 patients, and 19 of them achieved bone marrow blasts <5% before HSCT. The stem cell source was unmanipulated-related bone marrow or peripheral blood stem cells for nineteen patients and unrelated cord blood for eight. All patients received decitabine-containing and Bu/Cy-based myeloablative conditioning; 26 patients achieved initial engraftment. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GvHD) at 100 days were 65.4% and 42.3%, respectively. The incidence of cGvHD was 38.5%. The median follow-up was 26 (range 4-49) months after transplantation. By the end of follow-up, two patients died of complications and two died of disease progression. The probability of 3-year overall survival (OS) was 84.8% (95%CI, 71.1 to 98.5%). In summary, decitabine-containing myeloablative conditioning resulted in excellent outcomes for children with higher-risk MDS undergoing allogeneic HSCT.

A cotton mitochondrial alternative electron transporter, GhD2HGDH, induces early flowering by modulating GA and photoperiodic pathways.

D-2-hydroxyglutarate dehydrogenase (D2HGDH) is a mitochondrial enzyme containing flavin adenine dinucleotide FAD, existing as a dimer, and it facilitates the specific oxidation of D-2HG to 2-oxoglutarate (2-OG), which is a key intermediate in the tricarboxylic acid (TCA) cycle. A Genome-wide expression analysis (GWEA) has indicated an association between GhD2HGDH and flowering time. To further explore the role of GhD2HGDH, we performed a comprehensive investigation encompassing phenotyping, physiology, metabolomics, and transcriptomics in Arabidopsis thaliana plants overexpressing GhD2HGDH. Transcriptomic and qRT-PCR data exhibited heightened expression of GhD2HGDH in upland cotton flowers. Additionally, early-maturing cotton exhibited higher expression of GhD2HGDH across all tissues than delayed-maturing cotton. Subcellular localization confirmed its presence in the mitochondria. Overexpression of GhD2HGDH in Arabidopsis resulted in early flowering. Using virus-induced gene silencing (VIGS), we investigated the impact of GhD2HGDH on flowering in both early- and delayed-maturing cotton plants. Manipulation of GhD2HGDH expression levels led to changes in photosynthetic pigment and gas exchange attributes. GhD2HGDH responded to gibberellin (GA3) hormone treatment, influencing the expression of GA biosynthesis genes and repressing DELLA genes. Protein interaction studies, including yeast two-hybrid, luciferase complementation (LUC), and GST pull-down assays, confirmed the interaction between GhD2HGDH and GhSOX (Sulfite oxidase). The metabolomics analysis demonstrated GhD2HGDH's modulation of the TCA cycle through alterations in various metabolite levels. Transcriptome data revealed that GhD2HGDH overexpression triggers early flowering by modulating the GA3 and photoperiodic pathways of the flowering core factor genes. Taken together, GhD2HGDH positively regulates the network of genes associated with early flowering pathways.

Two Short-Wave UV Antimony(III) Sulfates Exhibiting Large Birefringence.

In the present work, we have successfully obtained two new UV antimony-based sulfates, NH4Sb(SO4)2 and Ca2Sb2O(SO4)4, by a conventional hydrothermal method. Interestingly, both compounds share similar structural building blocks, such as SbO4 seesaws and SO4 tetrahedra, yet they endow discrepant birefringence values measured at 546 nm with values of 0.150 and 0.114, respectively, owing to the different distortions of the SbO4 groups with SCALP electrons. Moreover, both compounds display large band gaps (4.32 and 4.43 eV, respectively), so they can be used as short-wavelength UV birefringent materials. Moreover, NH4Sb(SO4)2 is a noncentrosymmetric compound, showing a frequency doubling effect of 0.2 × KDP. Detailed structural analyses and calculations confirm the source of superior optical performance and the reasons for the different birefringence of the two compounds. This work provides ideas for the following discovery of antimony-based optical materials with excellent properties.

Refined Sea Salt Markers for Coastal Cities Facilitating Quantification of Aerosol Aging and PM2.5 Apportionment.

Sea salt (ss) aerosols in PM2.5 are often quantified through source apportionment by applying sodium (Na+) and chloride (Cl-) as the markers, but both markers can be substantially emitted from anthropogenic sources. In this study, we differentiate ss from nonss (nss) portions of Na+ and Cl- to better apportion PM2.5 in a coastal tropical urban environment. Size-resolved ionic profiles accounting for Cl- depletion of aged ss were applied to 162-day measurements during 2012 and 2018-2019. Results show that the nss (likely anthropogenic) portions, on average, account for 50-80% of total Na+ and Cl- in submicron aerosols (PM1). This corresponds to up to 2.5 µg/m3 of ss in submicron aerosols that can be ∼10 times overestimated if one attributes all Na+ and Cl- in PM1 to ss. Employing the newly speciated ss- and nss-portions of Na+ and Cl- to source apportionment of urban PM2.5 via positive matrix factorization uncovers a new source of transported anthropogenic emissions during the southwest monsoon, contributing to 12-15% of PM2.5. This increases anthropogenic PM2.5 by ≥19% and reduces ss-related PM2.5 by >30%. In addition to demonstrating Cl- depletion (aging) in submicron aerosols and quantifying ssNa+, nssNa+, ssCl-, as well as nssCl- therein, the refined PM2.5 apportionment resolves new insights on PM2.5 of anthropogenic origins in urban environments, useful to facilitate policy making.

PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.

BACKGROUND: Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer. METHODS: The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between tumour biomarkers and the postoperative pathological complete response (pCR) were explored. RESULTS: Forty-five patients completed neoadjuvant chemotherapy and final surgery, of which 26 (58%) achieved a pCR. Among all driver gene mutations, PIK3CA mutation was screened out for having a significant relationship with the treatment response. The pCR rate of patients with wild-type PIK3CA was significantly higher than patients with mutated PIK3CA (80.8% vs. 26.3%; P = 0.00057), and remained significant after a multiple comparison adjustment (Padjusted = 0.024). We further evaluated the predictive value with logistic regression model of clinical features, genetic biomarkers or both, an AUC of 0.912 (95% CI: 0.827-0.997) was achieved in the integrated model. CONCLUSIONS: Our data suggest that HER2-positive breast cancers with activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy.

A review of biomolecules conjugated lanthanide up-conversion nanoparticles-based fluorescence probes in food safety and quality monitoring applications.

Upconversion nanoparticles (UCNPs) are known to possess unique characteristics, which allow them to overcome a number of issues that plague traditional fluorescence probes. UCNPs have been employed in a variety of applications, but it is arguably in the realm of optical sensors where they have shown the most promise. Biomolecule conjugated UCNPs-based fluorescence probes have been developed to detect and quantify a wide range of analytes, from metal ions to biomolecules, with great specificity and sensitivity. In this review, we have given much emphasis on the recent trends and progress in the preparation strategies of bioconjugated UCNPs and their potential application as fluorescence sensors in the trace level detection of food industry-based toxicants and adulterants. The paper discusses the preparation and functionalisation strategies of commonly used biomolecules over the surface of UCNPs. The use of different sensing strategies namely heterogenous and homogenous assays, underlying fluorescence mechanisms in the detection process of food adulterants are summarized in detail. This review might set a precedent for future multidisciplinary research including the development of novel biomolecules conjugated UCNPs for potential applications in food science and technology.

Characterization and Reactivity Studies of Mononuclear Tetrahedral Copper(II)-Halide Complexes.

Structures, physicochemical properties, and reactivity of the whole series of copper(II)-halide complexes (1X; X = F, Cl, Br, and I) were examined using a TMG3tach tridentate supporting ligand consisting of cis,cis-1,3,5-triaminocyclohexane (tach) and N,N,N',N'-tetramethylguanidine (TMG). The tach ligand framework with the bulky and strongly electron-donating TMG substituents enforces the copper(II) complexes to take a tetrahedral geometry, as inferred from the electron paramagnetic resonance (EPR) spectra, exhibiting relatively large gz and small Az values. The electronic absorption spectra of 1X agreed with the simulation spectra obtained by time-dependent density functional theory (TD-DFT) calculations on a slightly distorted tetrahedral geometry. 1I and 1Br gradually decomposed to generate the corresponding copper(I) complex and halide radical X•, and in the case of 1Br, intramolecular hydroxylation of a methyl group of the TMG substituent took place under aerobic conditions, which may be caused by the reaction of the generated copper(I) complex and dioxygen (O2), generating a reactive oxygen species. 1X except 1I showed hydrogen atom abstraction (HAA) reactivity toward 1,4-cyclohexadiene (CHD), where 1F exhibited the highest reactivity with a second-order rate constant as 1.4 × 10-3 M-1 s-1 at 25 °C. Such an HAA reactivity can be attributed to the higher basicity of F- and/or large bond dissociation free energy of conjugate acid H-F as well as the unstable copper(II) electronic state in the tetrahedral geometry.

Topical medications for the treatment of recurrent aphthous stomatitis: A network meta-analysis.

BACKGROUND: The present network meta-analysis aims to answer the question "what is the best topical intervention for the treatment of recurrent aphthous stomatitis that can provide an acceptable pain relief and promote wound healing?" METHODS: From inception to October 2022, PubMed, Embase, Scopus, Cochrane Library, and China National Knowledge Infrastructure were searched to identify all potentially eligible randomized controlled trials. The primary outcomes were pain scores and/or healing time, while the secondary outcomes were the associated side effects. The Bayesian network meta-analysis accompanied by a random effect model and 95% credible intervals were calculated. RESULTS: Forty-three randomized controlled trials with a total of 3067 participants, comparing 20 different topical medications, were included. Concerning pain reduction, the network meta-analysis failed to show any statistically significant differences when different topical treatments were compared together or even with a placebo at different time intervals. Except for doxycycline, which showed a statistically significant difference in terms of accelerating healing time, other topical interventions showed no statistically significant differences when compared with placebo or with each other. CONCLUSION: Within the limitations of the current network meta-analysis, it seems that: A low to moderate quality of evidence showed no superiority of any topical treatment over others concerning pain reduction, although rank probability tests revealed sucralfate, doxycycline, hyaluronic acid, and chamomile as the most efficacious treatment options at different evaluation times. Hence, further well-designed clinical trials with larger sample sizes are warranted. Topical doxycycline was shown to be the most efficacious intervention in promoting healing of recurrent aphthous stomatitis.

The association between a novel inflammatory biomarker, systemic inflammatory response index and the risk of diabetic cardiovascular complications.

BACKGROUND AND AIM: Systemic inflammatory response index (SIRI) is a novel inflammatory biomarker. The relationship between SIRI and the risk of diabetic cardiovascular complications is still unclear. The purpose of our study was to address the correlation between SIRI and the risk of cardiovascular diseases (CVD) in diabetes mellitus (DM) patients. METHODS AND RESULTS: A total of 8759 individuals were selected from the National Health and Nutrition Examination Survey (NHANES) (2015-2020) in our study. Comparing with control (n = 6446) and pre-DM (n = 350) individuals, the DM patients (n = 1963) show the higher SIRI level (all P < 0.001) and prevalence of CVD (all P < 0.001). Furthermore, in a fully adjusted model, we observed the increase of tertiles of SIRI was a risk factor for CVD in DM patients (the middle tertile: 1.80, 95% CI: 1.13-3.13; the highest tertile: 1.91, 95% CI: 1.03-3.22; all P < 0.05), while the relationship between hypersensitive CRP (hs-CRP) and the risk of diabetic cardiovascular complications was not observed (all P > 0.05). Furthermore, the SIRI tertiles-CVD association was significant strongly in patients with high body mass index (BMI; >24 kg/m2) than in those with a low BMI (≤24 kg/m2, P for interaction = 0.045). Using restricted cubic splines, we observed a dose-response relation between lg SIRI and the risk of CVD in DM patients. CONCLUSIONS: The elevated SIRI was independently associated with the increased risk of CVD in the DM population with a high BMI (>24 kg/m2), and its clinical value is greater than hs-CRP.

Microbial and metabolic features in renal transplant recipients with post-transplantation diabetes mellitus.

OBJECTIVE: Post-transplantation diabetes mellitus (PTDM) is a common complication in renal transplant recipients (RTRs). Gut microbiome plays important roles in a variety of chronic metabolic diseases, but its association with the occurrence and development of PTDM is still unknown. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of PTDM. METHODS: A total of 100 RTRs fecal samples were collected in our study. Among them, 55 samples were submitted to Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of RTRs were comprehensively characterized. RESULTS: The species Dialister invisus was significantly associated with fasting plasma glucose (FPG). The functions of tryptophan and phenylalanine biosynthesis were enhanced in RTRs with PTDM, while the functions of fructose and butyric acid metabolism were reduced. Fecal metabolome analysis indicated that RTRs with PTDM had unique metabolite distribution characteristics, and two differentially expressed specific metabolites were significantly correlated with FPG. The correlation analysis of gut microbiome and metabolites showed that gut microbiome had an obvious effect on the metabolic characteristics of RTRs with PTDM. Moreover, the relative abundance of microbial function is associated with the expression of several specific gut microbiome and metabolites. CONCLUSIONS: Our study identified the characteristics of gut microbiome and fecal metabolites in RTRs with PTDM, and we also found two important metabolites and a bacterium were significantly associated with PTDM, which might be used as novel targets in the research field of PTDM.

The gut microbiome and metabolome in kidney transplant recipients with normal and moderately decreased kidney function.

BACKGROUND: The kidney transplant recipients (KTRs) were diagnosed with Chronic Kidney Disease after transplantation (CKD-T). CKD-T can be affected by the microbial composition and metabolites. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of CKD-T. METHODS: We collected 100 fecal samples of KTRs and divided them into two groups according to the stage progression of CKD-T. Among them, 55 samples were analyzed by Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of KTRs were comprehensively characterized. RESULTS: As well as significant differences in gut microbiome diversity between the CKD G1-2T group and CKD G3T group. Eight flora including Akkermansia were found to be enriched in CKD G3T group. As compared with CKD G1-2T group, the relative abundance of some amino acid metabolism, glycerophospholipid metabolism, amino acid biosynthesis, carbohydrate metabolism and purine metabolism in CKD G3T group were differential expressed significantly. In addition, fecal metabolome analysis indicated that CKD G3T group had a unique metabolite distribution characteristic. Two differentially expressed metabolites, N-acetylornithine and 5-deoxy-5'-(Methylthio) Adenosine, were highly correlated with serum creatinine, eGFR and cystatin C. The enrichment of gut microbial function in CKD-T is correlated with the expression of gut metabolites. CONCLUSION: Gut microbiome and metabolites in the progression of CKD-T display some unique distribution and expression characteristics. The composition of the gut microbiome and their metabolites appears to be different between patients with CKD G3T and those with CKD G1-2T.

Unanswered questions on the airborne transmission of COVID-19.

Policies and measures to control pandemics are often failing. While biological factors controlling transmission are usually well explored, little is known about the environmental drivers of transmission and infection. For instance, respiratory droplets and aerosol particles are crucial vectors for the airborne transmission of the severe acute respiratory syndrome coronavirus 2, the causation agent of the coronavirus 2019 pandemic (COVID-19). Once expectorated, respiratory droplets interact with atmospheric particulates that influence the viability and transmission of the novel coronavirus, yet there is little knowledge on this process or its consequences on virus transmission and infection. Here we review the effects of atmospheric particulate properties, vortex zones, and air pollution on virus survivability and transmission. We found that particle size, chemical constituents, electrostatic charges, and the moisture content of airborne particles can have notable effects on virus transmission, with higher survival generally associated with larger particles, yet some viruses are better preserved on small particles. Some chemical constituents and surface-adsorbed chemical species may damage peptide bonds in viral proteins and impair virus stability. Electrostatic charges and water content of atmospheric particulates may affect the adherence of virion particles and possibly their viability. In addition, vortex zones and human thermal plumes are major environmental factors altering the aerodynamics of buoyant particles in air, which can strongly influence the transport of airborne particles and the transmission of associated viruses. Insights into these factors may provide explanations for the widely observed positive correlations between COVID-19 infection and mortality with air pollution, of which particulate matter is a common constituent that may have a central role in the airborne transmission of the novel coronavirus. Supplementary Information: The online version contains supplementary material available at 10.1007/s10311-022-01557-z.

Exploiting the Type I-B CRISPR Genome Editing System in Thermoanaerobacterium aotearoense SCUT27 and Engineering the Strain for Enhanced Ethanol Production.

Thermoanaerobacterium aotearoense strain SCUT27 is a potential industrial biofuel-producing strain because of its broad substrate spectrum, especially the ability to co-use glucose and xylose. The bottleneck hindering the development of strain SCUT27 is the lack of selective markers for polygene manipulation in this thermophilic bacterium. In this study, the endogenous type I-B clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system was developed for multiplex genome editing of strain SCUT27. The protospacer-adjacent motif was identified by in silico analysis and verified with orotidine-5'-phosphate decarboxylase (pyrF) or lactate dehydrogenase (ldh) as the editing target. The type I-B CRISPR/Cas system was functional in strain SCUT27 with 58.3% to 100% editing efficiency. A multiplex genome editing method based on thymidine kinase (tdk) as a negative selection marker was developed, and strain SCUT27/Δtdk/Δldh/ΔargR, in which ldh and the arginine repressor (argR) were knocked out successively, was successfully obtained. Strain SCUT27/Δtdk/Δldh/ΔargR exhibited prominent advantages over wild-type SCUT27 in ethanol production, with significantly improved ability to metabolize xylose. IMPORTANCE Thermophilic microbes have attracted great attention as potential candidates for production of biofuels and chemicals from lignocellulose because of their thermal tolerance and wide substrate spectra. The ability to edit multiple genes using the native type I-B CRISPR/Cas system would speed up engineering of Thermoanaerobacterium aotearoense strain SCUT27 for higher ethanol production from lignocellulosic hydrolysates. Here, we produced a mutant strain, T. aotearoense SCUT27/Δtdk/Δldh/ΔargR, using the native CRISPR/Cas system. The engineered strain showed satisfactory performance with improved ethanol productivity from various lignocellulosic hydrolysates. Our data lay the foundations for development of this thermophilic microbe into an excellent ethanol producer using lignocellulosic hydrolysates. The methods described here may also provide a reference to develop multigene editing methods for other microorganisms.

Association between short-term exposure to ambient air pollution and biomarkers of coagulation: A systematic review and meta-analysis.

Ambient air pollution is one of the major global risk factors for cardiovascular health, and coagulation changes have been proposed to mediate this risk. Plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), soluble P-selectin (sP-selectin) and tissue plasminogen activator (t-PA) are major coagulation biomarkers. However, there has been no systematic meta-analysis to summarize associations of ambient air pollution with these coagulation biomarkers. To assess the overall associations between ambient particulate matter (PM2.5, PM10), ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO) and major coagulation biomarkers including PAI-1, vWF, sP-selectin and t-PA based on the existing epidemiological research. We performed a systematic literature search of publications reporting the associations of ambient air pollutants (PM2.5, PM10, O3, NO2, and CO) with coagulation biomarkers (PAI-1, vWF, sP-selectin and t-PA) in PubMed, Web of Science, EMBASE, and Scopus databases as of April 5, 2022. Then, we performed a random-effect meta-analysis, which included 27 articles, and then identified the potential sources of heterogeneity. The pooled percent changes of coagulation biomarkers per 10 µg/m3 increase in short-term exposure to ambient PM2.5 were 2.43% (95% CI: 0.59%, 4.29%) in PAI-1, 1.08% (95% CI: 0.21%, 1.96%) in vWF and 1.14% (95% CI: 0.59%, 1.68%) in sP-selectin, respectively. We also found significant associations of short-term exposure to ambient O3 with PAI-1 (1.62%, 95% CI: 0.01%, 3.25%), sP-selectin (9.59%, 95% CI:2.78%, 16.86%) and t-PA (0.45%, 95% CI: 0.02%, 0.88%), respectively. Short-term exposures to ambient PM10, NO2 and CO were not significantly associated with changes in coagulation biomarkers. In conclusion, short-term exposures to PM2.5 and O3 are associated with significant increases in coagulation biomarkers, suggesting an activated coagulation state upon air pollution exposure.

ASDB: A comprehensive omics database for Anopheles sinensis.

Anopheles sinensis is a key disease vector for human malaria and parasitic diseases such as malayan filariasis, and it is considered to be one of the most important malaria vectors in China and Southeast Asia. As high-throughput sequencing and assembly technology are widely used in An. sinensis, a lot of omics data have been generated, and abundant genome, mRNA transcriptome, miRNA transcriptome and resequencing results have been accumulated. In addition, lots of valuable morphological images and publications have been produced with the in-depth studies on An. sinensis. However, the increased quantity, variety, and structure complexity of the omics data create inconveniences for researchers to use and manage this information. We have built an An. sinensis omics database (ASDB, http://asdb.jungleran.com/) - a comprehensive and integrated database to promote scientific research on An. sinensis. Docker was used to deploy a development environment and Drupal to build ASDB. ASDB provides a Blast tool to do sequence alignment of genome sequence, gene sequence and protein sequence of An. sinensis. It also offers JBrowse (a next-generation genome visualization and analysis web platform) to facilitate researchers visualize the gene structure, non-coding RNA (include miRNA, snRNA, tRNA and so on) structure and genomic variation sites as desired. ASDB has integrated various latest omics data of An. Sinensis, including de novo genome and its annotation data, genome variation data (such as SNP and InDel), transcriptome and its expression value, miRNA expression value and miRNA-mRNA interaction, metagenomes. The database has also included the morphological images of different developmental stages and tissues, and important literatures associated with An. sinensis. ASDB provides a user-friendly search and displays pages. The integration of these resources will contribute to the study of basic biology and functional genome of An. sinensis.

The therapeutic efficacy and safety improvements of crizotinib prodrug micelles on breast cancer treatment.

Nowadays, breast cancer has become a major killer threatening women's health. MET is a receptor tyrosine kinase that upon binding of its ligand, hepatocyte growth factor, activates downstream pathways with diverse cellular functions which are important in the occurrence and development of breast cancer. Crizotinib (Cro) is a multi-target tyrosine kinase inhibitor targeting ALK gene recombination, MET gene amplification and ROS gene. Although Cro has the ideal treatment for breast cancer, Cro has stronger hepatotoxicity and lacks targeting capacity to the tumor cell, which limited Cro to effectively therapy breast cancer. In this study, we develop a novel prodrug micelle through polymerization reaction polymerizing Cro onto the chain to form POEG-b-PCro prodrug micelles, in which the drug loading capacity of Cro was significantly increased to improve the cumulant of the tumor. Pharmacokinetic and biodistribution studies illustrated that POEG-b-PCro prodrug micelles had a significant effect by improving Cro content in the tumor. Meanwhile, the antitumor mechanism of POEG-b-PCro prodrug micelles proved that POEG-b-PCro prodrug micelles had a stronger effect by reducing negative regulatory proteins. POEG-b-PCro prodrug micelles had splendid safety through safety study in vivo to account for POEG-b-PCro prodrug micelles. Therefore, POEG-b-PCro prodrug micelles are a promising drug delivery strategy for reducing toxicity and enhancing the efficacy of Cro.

Significance of paroxysmal nocturnal hemoglobinuria clone in immunosuppressive therapy for children with severe aplastic anemia. / é˜µå‘æ€§ç¡çœ æ€§è¡€çº¢è›‹ç™½å°¿å ‹éš†åœ¨å„¿ç«¥é‡åž‹å†ç”Ÿéšœç¢æ€§è´«è¡€å ç–«æŠ‘åˆ¶æ²»ç–—ä¸­çš„æ„ä¹‰.

OBJECTIVES: To study the association between paroxysmal nocturnal hemoglobinuria (PNH) clone and immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA). METHODS: A retrospective analysis was performed on the medical data of 151 children with SAA who were admitted and received IST from January 2012 to May 2020. According to the status of PNH clone, these children were divided into a negative PNH clone group (n=135) and a positive PNH clone group (n=16). Propensity score matching was used to balance the confounding factors, and the impact of PNH clone on the therapeutic effect of IST was analyzed. RESULTS: The children with positive PNH clone accounted for 10.6% (16/151), and the median granulocyte clone size was 1.8%. The children with positive PNH clone had an older age and a higher reticulocyte count at diagnosis (P<0.05). After propensity score matching, there were no significant differences in baseline features between the negative PNH clone and positive PNH clone groups (P>0.05). The positive PNH clone group had a significantly lower overall response rate than the negative PNH clone group at 6, 12, and 24 months after IST (P<0.05). The evolution of PNH clone was heterogeneous after IST, and the children with PNH clone showed an increase in the 3-year cumulative incidence rate of aplastic anemia-PNH syndrome (P<0.05). CONCLUSIONS: SAA children with positive PNH clone at diagnosis tend to have poor response to IST and are more likely to develop aplastic anemia-PNH syndrome.

Multishock to Quasi-Isentropic Compression of Dense Gaseous Deuterium-Helium Mixtures up to 120 GPa: Probing the Sound Velocities Relevant to Planetary Interiors.

Shock reverberation compression experiments on dense gaseous deuterium-helium mixtures are carried out to provide thermodynamic parameters relevant to the conditions in planetary interiors. The multishock pressures are determined up to 120 GPa and reshock temperatures to 7400 K. Furthermore, the unique compression path from shock-adiabatic to quasi-isentropic compressions enables a direct estimation of the high-pressure sound velocities in the unexplored range of 50-120 GPa. The equation of state and sound velocity provide particular dual perspectives to validate the theoretical models. Our experimental data are found to agree with several equation of state models widely used in astrophysics within the probed pressure range. The current data improve the experimental constraints on sound velocities in the Jovian insulating-to-metallic transition layer.

Mass Measurements of Neutron-Deficient Yb Isotopes and Nuclear Structure at the Extreme Proton-Rich Side of the N=82 Shell.

High-accuracy mass measurements of neutron-deficient Yb isotopes have been performed at TRIUMF using TITAN's multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS). For the first time, an MR-TOF-MS was used on line simultaneously as an isobar separator and as a mass spectrometer, extending the measurements to two isotopes further away from stability than otherwise possible. The ground state masses of ^{150,153}Yb and the excitation energy of ^{151}Yb^{m} were measured for the first time. As a result, the persistence of the N=82 shell with almost unmodified shell gap energies is established up to the proton drip line. Furthermore, the puzzling systematics of the h_{11/2}-excited isomeric states of the N=81 isotones are unraveled using state-of-the-art mean field calculations.