Hsa_circ_0001361 facilitates cell progression and glycolytic metabolism in neuroblastoma via interacting with mir-490-5p to induce TRIM2 upregulation.

Circular RNAs (circRNAs) can regulate the progression of neuroblastoma (NB) via miRNA/mRNA axis. This study aimed to investigate the functional mechanism of hsa_circ_0001361 in NB. Hsa_circ_0001361, miR-490-5p and tripartite motif 2 (TRIM2) were detected through reverse transcription-quantitative polymerase chain reaction. The proliferation ability was examined using cell counting kit-8 assay, colony formation assay and ethynyl-2'-deoxyuridine assay. Cell migration and invasion were assessed via transwell assay and wound healing assay. The protein levels were measured by western blot. Glycolysis was analyzed via commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed for target analysis. Hsa_circ_0001361 research in vivo was performed using xenograft tumor assay. Hsa_circ_0001361 was overexpressed in NB tissues and cells. Hsa_circ_0001361 downregulation suppressed cell proliferation, metastasis and glycolysis. Hsa_circ_0001361 served as a miR-490-5p sponge. The functions of hsa_circ_0001361 in NB cells were associated with miR-490-5p sponging effect. Hsa_circ_0001361 resulted in TRIM2 expression change via targeting miR-490-5p. MiR-490-5p acted as a tumor inhibitor in NB by downregulating TRIM2. Hsa_circ_0001361 knockdown reduced tumor growth in vivo through mediating miR-490-5p/TRIM2 axis. Our results suggested that hsa_circ_0001361 upregulated TRIM2 by absorbing miR-490-5p, thereby promoting cell malignant behaviors and glycolytic metabolism in NB.

Framework to Guide Health Professions Faculty Towards Increased Scholarship: Recommendations from the ASAHP Research, Discovery & Innovation Committee.

The Research, Discovery, and Innovation Publications (RDI-P) Task Force met from October 2020 to March 2022 to discuss ways in which the Association of Schools Advancing Health Professions (ASAHP) can help to guide institutional leaders to assign faculty effort and resources to enable success with the scholarship mission. The purpose of this White Paper is to propose a guiding framework for institutional leaders to determine their faculty's individual or team scholarly goals, assign appropriate percent efforts (funded/unfunded), and guide an overall faculty mix that balances required teaching loads with scholarly activities. The Task Force identified seven modifiable factors that can influence workload allocation for scholarship: 1. Limited range of the spectrum for effort distribution; 2. Matching expectations with reality; 3. Clinical training undervalued as adequate prep for translational or implementation research; 4. Limited support for mentorship availability; 5. Richer collaborations needed; 6. Finding resources and matching them to individual faculty needs; and 7. Further time for training needed. We then provide a set of recommendations to address the seven issues described. Finally, we describe four foci of scholarly activity (evidence-based educator; evidence-based clinical application; evidence-based collaborator; and evidence-based principal leader) with which a leader can develop strategies to align faculty interests and growth opportunities towards advancing scholarship.

Selective Synthesis and Structural Transformation of a 4-Ravel Containing Four Crossings and Featuring Cp*Rh/Ir Fragments.

Intricately interwoven topologies have been continually synthesized and are ultimately equally versatile and significant at the nanoscale level; however, reports concerning ravel structures, which are highly entwined new topological species, are extremely rare and fraught with tremendous synthesis challenges. To solve the synthesis problem, a tetrapodontic pyridine ligand L1 with two types of olefinic bond units and two Cp*M-based building blocks (E1, M=Rh; E2, M=Ir) featuring large conjugated planes was prepared to perform the self-assembly. Two unprecedented [5+10] icosanuclear molecular 4-ravels containing four crossings were obtained by parallel-displaced π···π interactions in a single-step strategy. Remarkably, reversible structural transformations between 4-ravel and the corresponding metallocage could be realized by concentration changes and solvent- and guest-induced effects. X-ray crystallographic data and NMR spectroscopy provide full confirmation of these phenomena.

The Diagnostic and Prognostic Value of miR-155 in Cancers: An Updated Meta-analysis.

BACKGROUND: MicroRNA-155 has been discussed as a biomarker in cancer diagnosis and prognosis. Although relevant studies have been published, the role of microRNA-155 remains uncertain because of insufficient data. METHODS: We conducted a literature search in PubMed, Embase, and Web of Science databases to obtain relevant articles and extract data to evaluate the role of microRNA-155 in cancer diagnosis and prognosis. RESULTS: The pooled results showed that microRNA-155 presented a remarkable diagnostic value in cancers (area under the curve = 0.90, 95% confidence interval (CI 0.87-0.92; sensitivity = 0.83, 95% CI 0.79-0.87; specificity = 0.83, 95% CI 0.80-0.86), which was maintained in the subgroups stratified by ethnicity (Asian and Caucasian), cancer types (breast cancer, lung cancer, hepatocellular carcinoma, leukemia, and pancreatic ductal adenocarcinoma), sample types (plasma, serum, tissue), and sample size (n >100 and n <100). In prognosis, a combined hazard ratio (HR) showed that microRNA-155 was significantly associated with poor overall survival (HR = 1.38, 95% CI 1.25-1.54) and recurrence-free survival (HR = 2.13, 95% CI 1.65-2.76), and was boundary significant with poor progression-free survival (HR = 1.20, 95% CI 1.00-1.44), but not significant with disease-free survival (HR = 1.14, 95% CI 0.70-1.85). Subgroup analyses in overall survival showed that microRNA-155 was associated with poor overall survival in the subgroups stratified by ethnicity and sample size. However, the significant association was maintained in cancer types subgroups of leukemia, lung cancer, and oral squamous cell carcinoma, but not in colorectal cancer, hepatocellular carcinoma, and breast cancer, and was maintained in sample types subgroups of bone marrow and tissue, but not in plasma and serum. CONCLUSIONS: Results from this meta-analysis demonstrated that microRNA-155 was a valuable biomarker in cancer diagnosis and prognosis.

In vivo base editing rescues photoreceptors in a mouse model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of retinal diseases that cause the progressive death of retinal photoreceptor cells and eventually blindness. Mutations in the ß-domain of the phosphodiesterase 6 (Pde6b) gene are the most identified causes of autosomal recessive RP. Clinically, there is no effective treatment so far that can stop the progression of RP and restore the vision. Here, we report a base editing approach in which adeno-associated virus (AAV)-mediated adenine base editor (ABE) delivering to postmitotic photoreceptors was conducted to correct the Pde6b mutation in a retinal degeneration 10 (rd10) mouse model of RP. Subretinal delivery of AAV8-ABE corrected Pde6b mutation with averaging up to 20.79% efficiency at the DNA level and 54.97% efficiency at the cDNA level without bystanders, restored PDE6B expression, preserved photoreceptors, and rescued visual function. RNA-seq revealed the preservation of genes associated with phototransduction and photoreceptor survival. Our data have demonstrated that base editing is a potential gene therapy that could provide durable protection against RP.

Machine learning analysis of breast ultrasound to classify triple negative and HER2+ breast cancer subtypes.

OBJECTIVES: Early diagnosis of triple-negative (TN) and human epidermal growth factor receptor 2 positive (HER2+) breast cancer is important due to its increased risk of micrometastatic spread necessitating early treatment and for guiding targeted therapies. This study aimed to evaluate the diagnostic performance of machine learning (ML) classification of newly diagnosed breast masses into TN versus non-TN (NTN) and HER2+ versus HER2 negative (HER2-) breast cancer, using radiomic features extracted from grayscale ultrasound (US) b-mode images. MATERIALS AND METHODS: A retrospective chart review identified 88 female patients who underwent diagnostic breast US imaging, had confirmation of invasive malignancy on pathology and receptor status determined on immunohistochemistry available. The patients were classified as TN, NTN, HER2+ or HER2- for ground-truth labelling. For image analysis, breast masses were manually segmented by a breast radiologist. Radiomic features were extracted per image and used for predictive modelling. Supervised ML classifiers included: logistic regression, k-nearest neighbour, and Naïve Bayes. Classification performance measures were calculated on an independent (unseen) test set. The area under the receiver operating characteristic curve (AUC), sensitivity (%), and specificity (%) were reported for each classifier. RESULTS: The logistic regression classifier demonstrated the highest AUC: 0.824 (sensitivity: 81.8%, specificity: 74.2%) for the TN sub-group and 0.778 (sensitivity: 71.4%, specificity: 71.6%) for the HER2 sub-group. CONCLUSION: ML classifiers demonstrate high diagnostic accuracy in classifying TN versus NTN and HER2+ versus HER2- breast cancers using US images. Identification of more aggressive breast cancer subtypes early in the diagnostic process could help achieve better prognoses by prioritizing clinical referral and prompting adequate early treatment.

Migration Dynamics of Fall Armyworm Spodoptera frugiperda (Smith) in the Yangtze River Delta.

The Yangtze River Delta, located in East China, is an important passage on the eastern pathway of the northward migration of fall armyworm Spodoptera frugiperda (Smith) in China, connecting China's year-round breeding area and the Huang-Huai-Hai summer maize area. Clarifying the migration dynamics of S. frugiperda in the Yangtze River Delta is of great significance for the scientific control and prevention of S. frugiperda in the Yangtze River Delta, even in the Huang-Huai-Hai region and Northeast China. This study is based on the pest investigation data of S. frugiperda in the Yangtze River Delta from 2019 to 2021, combining it with the migration trajectory simulation approach and the synoptic weather analysis. The result showed that S. frugiperda migrated to the Yangtze River Delta in March or April at the earliest, and mainly migrated to the south of the Yangtze River in May, which can be migrated from Guangdong, Guangxi, Fujian, Jiangxi, Hunan and other places. In May and June, S. frugiperda migrated further into the Jiang-Huai region, and its source areas were mainly distributed in Jiangxi, Hunan, Zhejiang, Jiangsu, Anhui and Hubei provinces. In July, it mainly migrated to the north of Huai River, and the source areas of the insects were mainly distributed in Jiangsu, Anhui, Hunan, Hubei and Henan. From the south of the Yangtze River to the north of the Huai River, the source areas of S. frugiperda were constantly moving north. After breeding locally, S. frugiperda can not only migrate to other regions of the Yangtze River Delta, but also to its surrounding provinces of Jiangxi, Hunan, Hubei, Henan, Shandong and Hebei, and even cross the Shandong Peninsula into Northeast China such as Liaoning and Jilin provinces. Trajectory simulation showed that the emigrants of S. frugiperda from the Yangtze River Delta moved northward, westward and eastward as wind direction was quite diverse in June-August. This paper analyzes the migration dynamics of S. frugiperda in the Yangtze River Delta, which has important guiding significance for the monitoring, early warning and the development of scientific prevention and control strategies for whole country.

Dual-AAV split prime editor corrects the mutation and phenotype in mice with inherited retinal degeneration.

The prime editor (PE) can edit genomes with almost any intended changes, including all 12 possible types of base substitutions, small insertions and deletions, and their combinations, without the requirement for double strand breaks or exogenous donor templates. PE demonstrates the possibility of correcting a variety of disease-causing mutations and might expand the therapeutic application of gene editing. In this study, PE was optimized based on a dual-adeno-associated virus (AAV) split-intein system in vitro by screening different split sites and split inteins. We found that splitting PE before amino acid 1105(Ser) of SpCas9 with Rma intein resulted in the highest on-target editing. The orientations of pegRNA and nicking sgRNA in the AAV vector were further optimized. To test the in vivo performance of the optimized dual-AAV split-PE3, it was delivered by subretinal injection in rd12 mice with inherited retinal disease Leber congenital amaurosis. The prime editors corrected the pathogenic mutation with up to 16% efficiency in a precise way, with no detectable off-target edits, restored RPE65 expression, rescued retinal and visual function, and preserved photoceptors. Our findings establish a framework for the preclinical development of PE and motivate further testing of PE for the treatment of inherited retinal diseases caused by various mutations.

A molecular atlas reveals the tri-sectional spinning mechanism of spider dragline silk.

The process of natural silk production in the spider major ampullate (Ma) gland endows dragline silk with extraordinary mechanical properties and the potential for biomimetic applications. However, the precise genetic roles of the Ma gland during this process remain unknown. Here, we performed a systematic molecular atlas of dragline silk production through a high-quality genome assembly for the golden orb-weaving spider Trichonephila clavata and a multiomics approach to defining the Ma gland tri-sectional architecture: Tail, Sac, and Duct. We uncovered a hierarchical biosynthesis of spidroins, organic acids, lipids, and chitin in the sectionalized Ma gland dedicated to fine silk constitution. The ordered secretion of spidroins was achieved by the synergetic regulation of epigenetic and ceRNA signatures for genomic group-distributed spidroin genes. Single-cellular and spatial RNA profiling identified ten cell types with partitioned functional division determining the tri-sectional organization of the Ma gland. Convergence analysis and genetic manipulation further validated that this tri-sectional architecture of the silk gland was analogous across Arthropoda and inextricably linked with silk formation. Collectively, our study provides multidimensional data that significantly expand the knowledge of spider dragline silk generation and ultimately benefit innovation in spider-inspired fibers.

Metabolic Syndrome-Related Knowledge, Attitudes, and Behavior among Indigenous Communities in Taiwan: A Cross-Sectional Study.

BACKGROUND: Metabolic syndrome is characterized by cardiovascular and chronic disease risk factors that cause health problems. Inequalities in medical resources and information present a challenge in this context. Indigenous communities may be unaware of their risk for metabolic syndrome. AIMS: This study explored factors associated with metabolic syndrome-related knowledge, attitudes, and behaviors among Taiwanese indigenous communities. METHODS: For this descriptive cross-sectional survey, we collected anthropometric data and used a self-administered questionnaire between 1 July 2016, to 31 July 2017, from a convenience sample of an indigenous tribe in eastern Taiwan. The response rate was 92%. RESULTS: The prevalence of metabolic syndrome was as high as 71%, and the average correct knowledge rate was 39.1%. The participants' self-management attitudes were mainly negative, and the self-management behaviors were low in this population. Stepwise regression analysis showed that knowledge, attitude, age, perception of physical condition, and body mass index, which accounted for 65% of the total variance, were the most predictive variables for self-management behaviors. CONCLUSIONS: This is the first study to report the relationship between metabolic syndrome knowledge, attitudes, and behaviors in an indigenous population. There is an urgent need to develop safety-based MetS health education programs that can provide access to the right information and enhance self-management approaches to lessen the growing burden of MetS in indigenous communities.

In vivo adenine base editing corrects newborn murine model of Hurler syndrome.

Mucopolysaccharidosis type I (MPS I) is a severe disease caused by loss-of-function mutation variants in the α-L-iduronidase (Idua) gene. In vivo genome editing represents a promising strategy to correct Idua mutations, and has the potential to permanently restore IDUA function over the lifespan of patients. Here, we used adenine base editing to directly convert A > G (TAG>TGG) in a newborn murine model harboring the Idua-W392X mutation, which recapitulates the human condition and is analogous to the highly prevalent human W402X mutation. We engineered a split-intein dual-adeno-associated virus 9 (AAV9) adenine base editor to circumvent the package size limit of AAV vectors. Intravenous injection of the AAV9-base editor system into MPS IH newborn mice led to sustained enzyme expression sufficient for correction of metabolic disease (GAGs substrate accumulation) and prevention of neurobehavioral deficits. We observed a reversion of the W392X mutation in 22.46 ± 6.74% of hepatocytes, 11.18 ± 5.25% of heart and 0.34 ± 0.12% of brain, along with decreased GAGs storage in peripheral organs (liver, spleen, lung and kidney). Collectively, these data showed the promise of a base editing approach to precisely correct a common genetic cause of MPS I in vivo and could be broadly applicable to the treatment of a wide array of monogenic diseases.

Hydroxysafflor Yellow A Exerts Neuroprotective Effect by Reducing Aß Toxicity Through Inhibiting Endoplasmic Reticulum Stress in Oxygen-Glucose Deprivation/Reperfusion Cell Model.

Ischemia stroke is thought to be one of the vascular risks associated with neurodegenerative diseases, such as Alzheimer's disease (AD). Hydroxysafflor yellow A (HSYA) has been reported to protect against stroke and AD, while the underlying mechanism remains unclear. In this study, SH-SY5Y cell model treated with oxygen-glucose deprivation/reperfusion (OGD/R) was used to explore the potential mechanism of HSYA. Results from cell counting kit-8 (CCK-8) showed that 10 µM HSYA restored the cell viability after OGD 2 hours/R 24 hours. HSYA reduced the levels of malondialdehyde and reactive oxygen species, while improved the levels of superoxide dismutase and glutathione peroxidase. Furthermore, apoptosis was inhibited, and the expression of brain-derived neurotrophic factor was improved after HSYA treatment. In addition, the expression levels of amyloid-ß peptides (Aß) and BACE1 were decreased by HSYA, as well as the expression levels of binding immunoglobulin heavy chain protein, PKR-like endoplasmic reticulum (ER) kinase pathway, and activating transcription factor 6 pathway, whereas the expression level of protein disulfide isomerase was increased. Based on these results, HSYA might reduce Aß toxicity after OGD/R by interfering with apoptosis, oxidation, and neurotrophic factors, as well as relieving ER stress.

Reactivation of Epstein-Barr Virus from Latency Involves Increased RNA Polymerase Activity at CTCF Binding Sites on the Viral Genome.

The ability of Epstein-Barr virus (EBV) to switch between latent and lytic infection is key to its long-term persistence, yet the molecular mechanisms behind this switch remain unclear. To investigate transcriptional events during the latent-to-lytic switch, we utilized Precision nuclear Run On followed by deep Sequencing (PRO-Seq) to map cellular RNA polymerase (Pol) activity to single-nucleotide resolution on the host and EBV genome in three different models of EBV latency and reactivation. In latently infected Mutu-I Burkitt lymphoma (BL) cells, Pol activity was enriched at the Qp promoter, the EBER region, and the BHLF1/LF3 transcripts. Upon reactivation with phorbol ester and sodium butyrate, early-phase Pol activity occurred bidirectionally at CTCF sites within the LMP-2A, EBER-1, and RPMS1 loci. PRO-Seq analysis of Akata cells reactivated from latency with anti-IgG and a lymphoblastoid cell line (LCL) reactivated with small molecule C60 showed a similar pattern of early bidirectional transcription initiating around CTCF binding sites, although the specific CTCF sites and viral genes were different for each latency model. The functional importance of CTCF binding, transcription, and reactivation was confirmed using an EBV mutant lacking the LMP-2A CTCF binding site. This virus was unable to reactivate and had disrupted Pol activity at multiple CTCF binding sites relative to the wild-type (WT) virus. Overall, these data suggest that CTCF regulates the viral early transcripts during reactivation from latency. These activities likely help maintain the accessibility of the viral genome to initiate productive replication. IMPORTANCE The ability of EBV to switch between latent and lytic infection is key to its long-term persistence in memory B cells, and its ability to persist in proliferating cells is strongly linked to oncogenesis. During latency, most viral genes are epigenetically silenced, and the virus must overcome this repression to reactivate lytic replication. Reactivation occurs once the immediate early (IE) EBV lytic genes are expressed. However, the molecular mechanisms behind the switch from the latent transcriptional program to begin transcription of the IE genes remain unknown. In this study, we mapped RNA Pol positioning and activity during latency and reactivation. Unexpectedly, Pol activity accumulated at distinct regions characteristic of transcription initiation on the EBV genome previously shown to be associated with CTCF. We propose that CTCF binding at these regions retains Pol to maintain a stable latent chromosome conformation and a rapid response to various reactivation signals.

Alphaherpesvirus upregulates NDRG1 expression to facilitate the nuclear import of viral UL31 and UL34 proteins.

Proteins UL31 and UL34 encoded by alphaherpesvirus are critical for viral primary envelopment and nuclear egress. We report here that pseudorabies virus (PRV), a useful model for research on herpesvirus pathogenesis, uses N-myc downstream regulated 1 (NDRG1) to assist the nuclear import of UL31 and UL34. PRV promoted NDRG1 expression through DNA damage-induced P53 activation, which was beneficial to viral proliferation. PRV induced the nuclear translocation of NDRG1, and its deficiency resulted in the cytosolic retention of UL31 and UL34. Therefore, NDRG1 assisted the nuclear import of UL31 and UL34. Furthermore, in the absence of the nuclear localization signal (NLS), UL31 could still translocate to the nucleus, and NDRG1 lacked an NLS, thus suggesting the existence of other mediators for the nuclear import of UL31 and UL34. We demonstrated that heat shock cognate protein 70 (HSC70) was the key factor in this process. UL31 and UL34 interacted with the N-terminal domain of NDRG1 and the C-terminal domain of NDRG1 bound to HSC70. Replenishment of HSC70ΔNLS in HSC70-knockdown cells, or interference in importin α expression, abolished the nuclear translocation of UL31, UL34, and NDRG1. These results indicated that NDRG1 employs HSC70 to facilitate viral proliferation in the nuclear import of PRV UL31 and UL34. This article is protected by copyright. All rights reserved.

Severe retinal hemorrhages at various levels with a serous retinal detachment in a pediatric patient with aplastic anemia-A case report.

Background: Aplastic anemia can cause ophthalmic abnormalities in patients. Vision loss in a child with aplastic anemia due to massive retinal hemorrhages at various levels is rare. Case presentation: A pediatric patient with aplastic anemia presented with retinal hemorrhages at multiple levels along with a serous retinal detachment in both eyes and subsequent retinal changes after pars plana vitrectomy. Conclusion: Anemia and thrombocytopenia in aplastic anemia could cause severe retinal hemorrhages and result in retinal atrophy and retinal edema. Vitrectomy can be performed to remove vitreous hemorrhage, but risk factors for retinal atrophy and edema need further investigation.

Mitigation of lamp oven and cavity oven temperature-induced frequency variation in rubidium atomic clock.

The long-term frequency stability of the rubidium atomic clock is primarily affected by temperature variations in the lamp oven and the cavity oven, which cause changes in light intensity, which are then converted into frequency variations. Therefore, we propose using light intensity variations to actively improve the cavity oven and lamp oven temperature sensitivity of the rubidium atomic clock. This is accomplished through research into the theory of the rubidium atomic frequency standard, specifically the effect of light intensity, lamp oven temperature, and cavity oven temperature on the frequency deviation. In previous work, we discovered the relationship between the light intensity and frequency deviation by combining this with our engineering expertise. Furthermore, some related experiments show that the method is feasible with the lamp oven and cavity oven temperature sensitivity of the rubidium atomic clock greatly improved, providing an effective way to improve the rubidium atomic clock's long-term frequency stability.

Efficacy of Fufang E'jiao Jiang in the Treatment of Patients with Qi and Blood Deficiency Syndrome: A Real-World Prospective Multicenter Study with a Patient Registry.

Objective: This nationwide, multicenter prospective observational study with a patient registry was designed to evaluate the efficacy of Fufang E'jiao Jiang (FEJ) in Chinese patients with Qi and blood deficiency syndrome (QBDS). Methods: QBDS patients were consecutively recruited from 81 investigational sites in China from July, 2019, to December, 2020. Patients who met the eligibility criteria were enrolled in a prospective registry database. Baseline characteristics and changes in scores on the traditional Chinese medicine (TCM) symptom evaluation scale for Qi and blood deficiency, the clinical global impression (CGI) scale, the fatigue scale-14 (FS-14), and the Pittsburgh sleep quality index (PSQI) were analyzed to determine the clinical efficacy of FEJ. Results: A total of 3,203 patients were recruited. The average remission rate (i.e., the sum of the cure rate and improvement rate) of the 20 symptoms of QBDS was 92.49% after 4 weeks of FEJ treatment, which was higher than at baseline; the rate increased to 94.69% at 8 weeks. The CGI scale revealed that the number of total remissions at 4 and 8 weeks was 3,120 (97.41%) and 415 (100%), respectively. The total FS-14 scores decreased by 1.67 ± 4.11 (p < 0.001) at 4 weeks and 1.72 ± 3.09 (p < 0.001) at 8 weeks of treatment. The PSQI scores were 6.6 ± 4.7 and 6.52 ± 3.07 at 4 and 8 weeks, respectively, which were significantly lower than the baseline scores (p < 0.001; p = 0.0033). Both the subhealth fatigue (SF) and iron deficiency anemia (IDA) groups showed significantly improved clinical symptoms of QBDS (p < 0.01). Between-group comparisons revealed significantly greater improvements in FS-14 and PSQI scores in the SF group than in the IDA group (p < 0.05). A multivariate logistic regression analysis showed that disease course, FS-14 score at baseline, and four-week FEJ doses were independent risk factors for the degree of symptom relief in QBDS patients (p < 0.05). Conclusion: In real-world settings, FEJ has a promising effect in treating QBDS and can significantly improve the severity of its symptoms.

Correlation of renal oxygenation with renal function in chronic kidney disease: a preliminary prospective study.

INTRODUCTION: Chronic hypoxia is prevalent in chronic kidney disease (CKD), and Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) provides noninvasive evaluation of renal oxygenation. This study aimed to explore the correlation of renal oxygenation evaluated by BOLD-MRI with renal function. METHODS: 97 non-dialysis patients with CKD stages 1-5 and healthy volunteers (HVs) were recruited in the study. Based on their estimated glomerular filtration rate (eGFR), the patients were divided into two groups: CKD stages 1-3 (CKD 1-3) and CKD stages 4-5 (CKD 4-5) . We measured cortical and medullary T2* (COT2* and MET2*) values in all participants by BOLD-MRI. Physiological indices were also recorded and compared among three groups. Correlation of T2* values with clinical characteristics were determined. RESULTS: The COT2* values were significantly higher than MET2* values in all participants. The COT2* and MET2* values of three groups were ranked as HV> CKD 1-3> CKD 4-5 (p< 0.0001). There were positive correlations between the COT2* values, MET2* values and eGFR, hemoglobin (r> 0.4, p< 0.01). The 24-h urinary protein (24-h Upr) shown weak correlation with the COT2* value (rs= -0.2301, p= 0.0265), and no correlation with the MET2* value (p> 0.05). Urinary microprotein, including urinary alpha1-microglobulin (α1-MG), urinary beta2-microglobulin (ß2-MG), and urinary retinol binding protein (RBP), was showed strong correlation with COT2* and MET2* values. According to analysis of receiver-operating characteristic (ROC) curve, we obtained the optimal cut-point between HV and CKD 1-3 were "< 61.17 ms" (sensitivity: 91.23%, specificity: 100%) for COT2* values and "< 35.00 ms" (sensitivity: 77.19%, specificity: 100%) for MET2* values, whereas COT2* values ("< 47.34 ms"; sensitivity: 90.00%, specificity: 92.98%) and MET2* values ("< 25.09 ms"; sensitivity: 97.50%, specificity: 80.70%) between CKD 1-3 and CKD 4-5. CONCLUSION: The decline of renal oxygenation reflected on T2* values, especially in cortex, may be an effective diagnostic-marker for early detection of CKD.

Efficient Fractionation and Catalytic Valorization of Raw Biomass in ϵ-Caprolactone and Water.

Efficient fractionation and utilization of the whole biomass is particularly attractive but remains a great challenge, owing to the recalcitrance of biomass. In this study, a simple and efficient approach is developed to obtain high-purity cellulose with a delignification degree of 97.5 % in ϵ-caprolactone and water. FTIR spectroscopy reveals that ϵ-caprolactone and water act in synergy to remove lignin from raw biomass and afford cellulose with clear macrofibrils. A linear positive correlation between the contents of hemicellulose and lignin is observed for the separated cellulose pulp. This mixed solvent exhibits good performance for the removal of lignin from various agricultural and forestry wastes. Moreover, nearly complete transformation of the whole biomass constituents is achieved with Ni-Al catalyst.

Evaluation and validation of the prognostic value of platelet indices in patients with leukemia.

Platelets (PLTs) are believed to play a role in the process by which tumors can accelerate their growth rate, as well as offer the physical and mechanical support necessary to evade the immunological system and metastasis. There is, however, no literature available if PLTs have a role in leukemia. It is significant for PLTs to play a part in hematological malignancies from a therapeutic standpoint and to have the capacity to serve as a prognostic marker in the evolution of leukemia. This is because PLTs play a crucial role in the development of cancer and tumors. In this study, it will be shown that PLT count can be used to predict long-term prognosis after chemotherapy especially in the case of acute myeloid leukemia patients. Furthermore, low PLT-to-lymphocyte ratio and mean PLT volume, as well as high PLT distribution width, are associated with poor prognosis and may represent a novel independent prognostic factor.