P300/CBP Regulates HIF-1-Dependent Sympathetic Activation and Hypertension by Intermittent Hypoxia.

Obstructive sleep apnea (OSA), a widespread breathing disorder, leads to intermittent hypoxia (IH). Patients with OSA and IH-treated rodents exhibit heightened sympathetic nerve activity and hypertension. Previous studies reported transcriptional activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) by HIF-1 (hypoxia-inducible factor-1) contribute to autonomic dysfunction in IH-treated rodents. Lysine acetylation, regulated by KATs (lysine acetyltransferases) and KDACs (lysine deacetylases), activates gene transcription and plays an important role in several physiological and pathological processes. This study tested the hypothesis that acetylation of HIF-1α by p300/CBP (CREB-binding protein) (KAT) activates Nox transcription, leading to sympathetic activation and hypertension. Experiments were performed on pheochromocytoma-12 cells and rats treated with IH. IH increased KAT activity, p300/CBP protein, HIF-1α lysine acetylation, HIF-1 transcription, and HIF-1 binding to the Nox4 gene promoter in pheochromocytoma-12 cells, and these responses were blocked by CTK7A, a selective p300/CBP inhibitor. Plasma norepinephrine (index of sympathetic activation) and blood pressures were elevated in IH-treated rats. These responses were associated with elevated p300/CBP protein, HIF-1α stabilization, transcriptional activation of Nox2 and Nox4 genes, and reactive oxygen species, and all these responses were absent in CTK7A-treated IH rats. These findings suggest lysine acetylation of HIF-1α by p300/CBP is an important contributor to sympathetic excitation and hypertension by IH.

Ratiometric Detection of Ochratoxin A Using a Regenerable COF-Au-MB-Apt Signal Probe on a Thermal-Regulated Sensor Module.

Ochratoxin A (OTA) frequently contaminates grains and consequently threatens human health. Herein, we develop a regenerable signal probe and apply it to a Au-based screen-printed electrode module (SPE) for OTA determination. The signal probe, containing a structural covalent organic framework, gold nanoparticles (AuNPs), indicative methylene blue (MB), and a highly selective aptamer, is synthesized with hydrothermal and self-assembly methods. The SPE is permanently functionalized with Prussian blue (PB), AuNPs, and semicomplementary ssDNA. The signal probe, absorbed onto this SPE via hybridization, is competitively expelled by OTA, providing a ratiometric readout of ΔIMB/IPB. Probe regeneration, to erase expired COF-Au-MB-Apt after each analysis, is established with the synergy of OTA-conducted Apt-ssDNA dissociation and on-chip thermal regulation. This advantage powerfully guarantees reduplicative analyses by avoiding irreversible Apt-OTA combination and accumulation on the sensing interface. Regenerations are performed in repetitive cycles (N = 7) with 98.5% reproduction efficiency, and IMB and IPB fluctuations are calculated as 1.45 and 1.12%. This method shows log-linear OTA response in a wide range from 0.2 pg/mL to 0.6 µg/mL, and the limit of detection is 0.12 pg/mL. During natural OTA determinations, recommended readouts match well with HPLC with less than 4.82% relative error.

Flexible-fabricated sensor module with programmable magnetic actuators coupled to L-cysteine functionalized Ag@Fe3O4 complexes for Cu2+ detection in fish tissues.

Heavy metal contamination for seafood, particularly fish, is arising great concerns, and consequentially it is necessary to develop a simple and direct detection method. In this work, Ag@Fe3O4 is successfully prepared by simple solvothermal method, and we present a flexible-fabricated sensor module with assembled programmable magnetic actuators. The resulting sensor integrates a three-electrode system with two programmable magnetic actuators at the bottom of the device, which regulates the amount of current by adjusting the brake to control the adsorption force and vibration. The L-Cysteine functionalized Ag@Fe3O4 is coated on the surface of the electrode, then the Cu2+ is dropped into the reaction tank. Its performance is studied by cyclic voltammetry and electrochemical impedance spectroscopy, and the key experimental conditions such as deposition potential, deposition time, and electrolyte pH are gradually optimized. Under optimal conditions, Cu2+ can be detected over a wide linear range (0.01 ~ 4 µM) and at a low LOD (0.34 nM). The results show that the proposed method has a good application prospect in the detection of Cu2+. This method is successfully applied to Cu2+ analysis in fish samples with an acceptable recovery of 93 ~ 102%.

Dynamic changes of gut bacterial communities present in larvae of Anoplophora glabripennies collected at different developmental stages.

The Asian long-horned beetle, Anoplophora glabripennies (Motschulsky), is a destructive wood-boring pest that is capable of killing healthy trees. Gut bacteria in the larvae of the wood-boring pest is essential for the fitness of hosts. However, little is known about the structure of the intestinal microbiome of A. glabripennies during larval development. Here, we used Illumina MiSeq high-throughput sequencing technology to analyze the larval intestinal bacterial communities of A. glabripennies at the stages of newly hatched larvae, 1st instar larvae and 4th instar larvae. Significant differences were found in larval gut microbial community structure at different larvae developmental stages. Different dominant genus was detected during larval development. Acinetobacter were dominant in the newly hatched larvae, Enterobacter and Raoultella in the 1st instar larvae, and Enterococcus and Gibbsiella in the 4th instar larvae. The microbial richness in the newly hatched larvae was higher than those in the 1st and 4th instar larvae. Many important functions of the intestinal microbiome were predicted, for example, fermentation and chemoheterotrophy functions that may play an important role in insect growth and development was detected in the bacteria at all tested stages. However, some specific functions are found to be associated with different development stages. Our study provides a theoretical basis for investigating the function of the intestinal symbiosis bacteria of A. glabripennies.

Powering mesoporous silica nanoparticles into bioactive nanoplatforms for antibacterial therapies: strategies and challenges.

Bacterial infection has been a major threat to worldwide human health, in particular with the ever-increasing level of antimicrobial resistance. Given the complex microenvironment of bacterial infections, conventional use of antibiotics typically renders a low efficacy in infection control, thus calling for novel strategies for effective antibacterial therapies. As an excellent candidate for antibiotics delivery, mesoporous silica nanoparticles (MSNs) demonstrate unique physicochemical advantages in antibacterial therapies. Beyond the delivery capability, extensive efforts have been devoted in engineering MSNs to be bioactive to further synergize the therapeutic effect in infection control. In this review, we critically reviewed the essential properties of MSNs that benefit their antibacterial application, followed by a themed summary of strategies in manipulating MSNs into bioactive nanoplatforms for enhanced antibacterial therapies. The chemically functionalized platform, photo-synergized platform, physical antibacterial platform and targeting-directed platform are introduced in details, where the clinical translation challenges of these MSNs-based antibacterial nanoplatforms are briefly discussed afterwards. This review provides critical information of the emerging trend in turning bioinert MSNs into bioactive antibacterial agents, paving the way to inspire and translate novel MSNs-based nanotherapies in combating bacterial infection diseases.

Childhood environment and adulthood food addiction: Testing the multiple mediations of life history strategies and attitudes toward self.

Food addiction is associated with both physical and mental health conditions, such as obesity and depression, and is considered a public health problem. Based on life history (LH) theory, this study aimed to test the association between unpredictable childhood environment and food addiction in adulthood and to examine LH strategies and attitudes toward self as psychological mediators of this association. A random sample of 1010 adults, aged from 18 to 88 years (44.8% male; Mage = 38.52, SDage = 14.53), voluntarily participated in an anonymous telephone survey conducted in Macao, China. The results of a path analysis showed the significant and positive direct effect of childhood unpredictability on food addiction and its negative association with slow LH strategy, which in turn was negatively correlated with food addiction. In addition, slow LH strategy and self-judgment, rather than self-kindness, acted as serial mediators in the association between childhood unpredictability and food addiction. These findings support the applicability of LH theory to understanding food addiction, as well as pointing to the potential risk effect of self-judgment for food addiction in adulthood. Self-judgment reduction may be a potential supplementary approach for future food addiction intervention.

Sponge-liked Silica Nanoporous Particles for Sustaining Release and Long-Term Antibacterial Activity of Natural Essential Oil.

To improve the sustained release and long-term antibacterial activity of Chimonanthus nitens Oliv. essential oil (CEO), novel sponge-liked nanoporous silica particles (SNP) were synthesized via the soft template method, which was employed as a biocompatible carrier to prepare spong-liked nanoporous silica particles loading with CEO (CEO-SNP) through physical adsorption. The structure and properties of the samples were characterized via N2 adsorption/desorption measurements, thermogravimetry (TGA), Fourier transform infrared, SEM and TEM. The result showed that the SNP exhibited an excellent loading capability of CEO up to 76.3%. The thermal stability and release behavior of the CEO were significantly improved via the physical adsorption of the SNP materials. The release profile of CEO was in accordance with the first-order kinetic model, which meant that the release mechanism was drug Fick's diffusion. The antibacterial evaluation results demonstrated that the CEO-SNP exhibited strong antibacterial activity against S. aureus, E. coli and P. aeruginosa. The antibacterial results have shown that the CEO-SNP could destroy the cell structure of bacteria, and result in the generation of oxidative stress and the release of nucleic acid. After storage of 30 d at 25 °C, the CEO-SNP still had the stronger antibacterial activity towards S. aureus, E. coli and P. aeruginosa in comparison with CEO. Therefore, the sponge-like silica nanoporous particles seemed to be a promising carrier for long-term stability and antibacterial delivery of CEO.

Similar gut bacteria composition in Apriona germari on two preferred host plants.

Apriona germari is one of the most serious wood-boring pests that cause damage to economic and landscaping trees and has adapted to a wide range of plants as diet. Gut bacteria play an important role in biology and ecology of herbivores, especially in growth and adaptation. To investigate how plant hosts shape A. germari gut microbiota, A. germari larvae were collected from Populus tomentosa and Malus pumilal, and gut microbiomes were sequenced based on 16S rDNA high-throughput sequencing technology. A total of 853,424 high-quality reads were obtained and clustered into 196 operational taxonomic units under a 97% similarity cutoff, which were annotated into 8 phyla, 10 classes, 21 orders, 34 families, 59 genera, and 39 species. Gibbsiella was the most dominant genus of intestinal bacteria, followed by Enterobacter and Acinetobacter. No significant difference was observed in larvae gut bacterial richness and diversity of A. germari collected from two hosts, though alpha diversity showed that the richness of gut bacteria in A. germari larvae collected on P. tomentosa was slightly higher than that in A. germari on M. pumilal, and beta diversity showed little difference between two host plants. The functional abundance analysis of the detected bacteria revealed fermentation, chemoheterotrophy, symbionts, and nitrate relative functions that highly possibly support wood-boring beetles to feed on woody tissues. Our study provided a theoretical basis for investigating the function of intestinal symbiosis bacteria of A. germari.

Comparative physiological and transcriptomic analysis of sesame cultivars with different tolerance responses to heat stress.

High temperature is the main factor affecting plant growth and can cause plant growth inhibition and yield reduction. Here, seedlings of two contrasting sesame varieties, i.e., Zheng Taizhi 3 (heat-tolerant) and SP19 (heat-sensitive), were treated at 43 °C for 10 days. The results showed that the relative electrical conductivity, hydrogen peroxide levels, and superoxide anion radical levels of both varieties increased significantly under high temperature stress. Additionally, dry matter accumulation and chlorophyll content decreased significantly, and the activities of peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) increased. However, under HT stress, the content of reactive oxygen species in Zheng Taizhi 3 was lower than that in SP19, and the activities of SOD, CAT, and POD as well as the chlorophyll content in Zheng Taizhi 3 were higher than those in SP19. Comparative transcriptome analysis identified 6736 differentially expressed genes (DEGs); 5526 DEGs (2878 up and 2648 down) were identified in Zheng Taizhi 3, and 5186 DEGs (2695 up and 2491 down) were identified in SP19, with 3976 overlapping DEGs. These DEGs included stress tolerance-related heat-shock proteins, as well as genes related to carbohydrate and energy metabolism, signal transduction, endoplasmic reticulum protein processing, amino acid metabolism, and secondary metabolism. Overall, our results showed that the heat tolerance of Zheng Taizhi 3 was attributed to a stronger antioxidant defense system, enabling the variety to avoid oxidative damage compared with the heat-sensitive SP19. Moreover, some specifically expressed and high-abundance genes in Zheng Taizhi 3 were involved in regulatory mechanisms related to heat tolerance, including plant hormone signal transduction and heat shock protein regulation, thereby enhancing heat tolerance. The study contributes to a deeper understanding of the underlying complex molecular mechanisms involved in the responses of sesame seedlings to heat stress and provides a potential strategy for heat-resistant new varieties. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01195-3.

Role of olfactory receptor78 in carotid body-dependent sympathetic activation and hypertension in murine models of chronic intermittent hypoxia.

Chronic intermittent hypoxia (CIH) is a hallmark manifestation of obstructive sleep apnea (OSA), a widespread breathing disorder. CIH-treated rodents exhibit activation of the sympathetic nervous system and hypertension. Heightened carotid body (CB) activity has been implicated in CIH-induced hypertension. CB expresses high abundance of olfactory receptor (Olfr) 78, a G-protein coupled receptor. Olfr 78 null mice exhibit impaired CB sensory nerve response to acute hypoxia. Present study examined whether Olfr78 participates in CB-dependent activation of the sympathetic nervous system and hypertension in CIH-treated mice and in hemeoxygenase (HO)-2 null mice experiencing CIH as a consequence of naturally occurring OSA. CIH-treated wild-type (WT) mice showed hypertension, biomarkers of sympathetic nerve activation, and enhanced CB sensory nerve response to hypoxia and sensory long-term facilitation (sLTF), and these responses were absent in CIH-treated Olfr78 null mice. HO-2 null mice showed higher apnea index (AI) (58 ± 1.2 apneas/h) than WT mice (AI = 8 ± 0.8 apneas/h) and exhibited elevated blood pressure (BP), elevated plasma norepinephrine (NE) levels, and heightened CB sensory nerve response to hypoxia and sLTF. The magnitude of hypertension correlated with AI in HO-2 null mice. In contrast, HO-2/Olfr78 double null mice showed absence of elevated BP and plasma NE levels and augmented CB response to hypoxia and sLTF. These results demonstrate that Olfr78 participates in sympathetic nerve activation and hypertension and heightened CB activity in two murine models of CIH.NEW & NOTEWORTHY Carotid body (CB) sensory nerve activation is essential for sympathetic nerve excitation and hypertension in rodents treated with chronic intermittent hypoxia (CIH) simulating blood O2 profiles during obstructive sleep apnea (OSA). Here, we report that CIH-treated mice and hemeoxygenase (HO)-2-deficient mice, which show OSA phenotype, exhibit sympathetic excitation, hypertension, and CB activation. These effects are absent in Olfr78 null and Olfr78/HO-2 double null mice.

Gaseous transmitter regulation of hypoxia-evoked catecholamine secretion from murine adrenal chromaffin cells.

Emerging evidence suggests that gaseous molecules, carbon monoxide (CO), and hydrogen sulfide (H2S) generated by heme oxygenase (HO)-2 and cystathionine γ-lyase (CSE), respectively, function as transmitters in the nervous system. Present study examined the roles of CO and H2S in hypoxia-induced catecholamine (CA) release from adrenal medullary chromaffin cells (AMCs). Studies were performed on AMCs from adult (≥6 wk of age) wild-type (WT), HO-2 null, CSE null, and HO-2/CSE double null mice of either gender. CA secretion was determined by carbon fiber amperometry and [Ca2+]i by microflurometry using Fura-2. HO-2- and CSE immunoreactivities were seen in WT AMC, which were absent in HO-2 and CSE null mice. Hypoxia (medium Po2 30-38 mmHg) evoked CA release and elevated [Ca2+]i. The magnitude of hypoxic response was greater in HO-2 null mice and in HO inhibitor-treated WT AMC compared with controls. H2S levels were elevated in HO-2 null AMC. Either pharmacological inhibition or genetic deletion of CSE prevented the augmented hypoxic responses of HO-2 null AMC and H2S donor rescued AMC responses to hypoxia in HO-2/CSE double null mice. CORM3, a CO donor, prevented the augmented hypoxic responses in WT and HO-2 null AMC. CO donor reduced H2S levels in WT AMC. The effects of CO donor were blocked by either ODQ or 8pCT, inhibitors of soluble guanylyl cyclase (SGC) or protein kinase G, respectively. These results suggest that HO-2-derived CO inhibits hypoxia-evoked CA secretion from adult murine AMC involving soluble guanylyl cyclase (SGC)-protein kinase G (PKG)-dependent regulation of CSE-derived H2S.NEW & NOTEWORTHY Catecholamine secretion from adrenal chromaffin cells is an important physiological mechanism for maintaining homeostasis during hypoxia. Here, we delineate carbon monoxide (CO)-sensitive hydrogen sulfide (H2S) signaling as an important mediator of hypoxia-induced catecholamine secretion from murine adrenal chromaffin cells. Heme oxygenase-2 derived CO is a physiological inhibitor of catcholamince secretion by hypoxia and the effects of CO involve inhibition of cystathionine γ-lyase-derived H2S production through soluble guanylyl cyclase-protein kinase G signaling cascade.

Bidirectional modulation of HIF-2 activity through chemical ligands.

Hypoxia-inducible factor-2 (HIF-2) is a heterodimeric transcription factor formed through dimerization between an oxygen-sensitive HIF-2α subunit and its obligate partner subunit ARNT. Enhanced HIF-2 activity drives some cancers, whereas reduced activity causes anemia in chronic kidney disease. Therefore, modulation of HIF-2 activity via direct-binding ligands could provide many new therapeutic benefits. Here, we explored HIF-2α chemical ligands using combined crystallographic, biophysical, and cell-based functional studies. We found chemically unrelated antagonists to employ the same mechanism of action. Their binding displaced residue M252 from inside the HIF-2α PAS-B pocket toward the ARNT subunit to weaken heterodimerization. We also identified first-in-class HIF-2α agonists and found that they significantly displaced pocket residue Y281. Its dramatic side chain movement increases heterodimerization stability and transcriptional activity. Our findings show that despite binding to the same HIF-2α PAS-B pocket, ligands can manifest as inhibitors versus activators by mobilizing different pocket residues to allosterically alter HIF-2α-ARNT heterodimerization.

Triphenyl-sesquineolignan analogues derived from Illicium simonsii Maxim exhibit potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) by disrupting bacterial membranes.

Infections caused by clinical methicillin-resistant Staphylococcus aureus (MRSA) are a serious public problem. Triphenyl-sesquineolignans from Illicium genus possess antibacterial activity, but few researches have reported their antibacterial spectrums, structure-activity relationships (SARs) and antibacterial mechanism. In this study, three triphenyl-sesquineolignans, dunnianol (1), macranthol (2) and isodunnianol (3) were isolated from the stems and leaves of I. simonsii Maxim, and seven dunnianol derivatives were prepared through esterification, etherification and halogenation reactions. Among all triphenyl-sesquineolignan analogues, compound 6 showed the best antibacterial activity against four Gram-positive bacteria (MICs = 1-2 µg/mL) and ten clinical MRSA strains (MICs = 2-8 µg/mL), and also exhibited characteristics of killing MRSA more rapidly than tigecycline. Meanwhile, compound 6 did not only show a low probability of drug resistance development, but also exhibited relatively low hemolysis, and good stability in 50% plasma. Further mechanism studies revealed that 6 could kill bacterial strains by disrupting bacterial membranes. These results suggested that 6 may be developed into a new antibacterial candidate for combating MRSA infections.

Mental distress during the COVID-19 pandemic: Its association with public perceptions toward government's pandemic responses and lifestyle changes.

In order to propose better mental health interventions under the pandemic threat, the present study aimed to investigate whether depression and anxiety are associated to Chinese adults' perceptions of government's pandemic responses and the personal lifestyle changes imposed by those responses during the COVID-19 pandemic. We used a telephone survey with random sampling and obtained a probability community sample of 616 adults (39.1% men; M age = 41.7, SD age = 16.3) in Macao, China in April 2020. The prevalence of 8.8% probable depression and 12.0% probable anxiety was observed in this sample. Positive perceptions toward government's pandemic responses were found to be negatively associated with probable depression and probable anxiety (ORu = .36 and .41, p < .05). Three lifestyle-changing stressors (i.e., increased family conflict, friendship deterioration, and weight gain), were commonly reported (29.9, 27.5, and 43.0% respectively), and displayed positive associations with probable depression (ORu = 1.67 to 1.87, p < .05) and probable anxiety (ORu = 1.54 to 2.10, p < .05). Our findings suggest protective effects of perceived trust and satisfaction regarding government's pandemic responses against mental distress and the potential mental health threats from three pandemic-specific lifestyle-changing stressors. These findings can inform clinicians and policymakers to better prepare for the mental health impacts of the current and future pandemics.

Identification and partial purification of thuricin 4AJ1 produced by Bacillus thuringiensis.

Thuricin 4AJ1, produced by Bacillus thuringiensis strain 4AJ1, showed inhibition activity against Bacillus cereus 0938 and ATCC 10987. It began to appear in the stationary phase and reached its maximum activity level of 209.958 U at 18 h against B. cereus 0938 and 285.689 U at 24 h against B. cereus ATCC 10987. Tricine-SDS-PAGE results showed that the partly purified thuricin 4AJ1 was about 6.5 kDa. The molecular weights of the known B. thuringiensis bacteriocins and the ones obtained by the two mainstream websites for predicting bacteriocins were inconsistent with the size of the thuricin 4AJ1, indicating that the bacteriocin obtained in this study may have a novel structure. Based on the biochemical properties, the thuricin 4AJ1 activities increased after treatment with proteinase K and lipase II, and were not affected by a-amylase, catalase, α-chymotrypsin VII and α-chymotrypsin II. It was heat tolerant, being active up to 90º C. In the pH 3-10 range, it maintained most of its activity. Finally, the sensitivity of the strain 4AJ1 to commonly used antibiotics was tested. In view of its stability and antibacterial activity, thuricin 4AJ1 may be applied as a food biopreservative.

In situ growth in early lung adenocarcinoma may represent precursor growth or invasive clone outgrowth-a clinically relevant distinction.

The switch from in situ to invasive tumor growth represents a crucial stage in the evolution of lung adenocarcinoma. However, the biological understanding of this shift is limited, and 'Noguchi Type C' tumors, being early lung adenocarcinomas with mixed in situ and invasive growth, represent those that are highly valuable in advancing our understanding of this process. All Noguchi Type C adenocarcinomas (n = 110) from the LATTICE-A cohort were reviewed and two patterns of in situ tumor growth were identified: those deemed likely to represent a true shift from precursor in situ to invasive disease ('Noguchi C1') and those in which the lepidic component appeared to represent outgrowth of the invasive tumor along existing airspaces ('Noguchi C2'). Overall Ki67 fraction was greater in C2 tumors and only C1 tumors showed significant increasing Ki67 from in situ to invasive disease. P53 positivity was acquired from in situ to invasive disease in C1 tumors but both components were positive in C2 tumors. Likewise, vimentin expression was increased from in situ to invasive tumor in C1 tumors only. Targeted next generation sequencing of 18 C1 tumors identified four mutations private to the invasive regions, including two in TP53, while 6 C2 tumors showed no private mutations. In the full LATTICe-A cohort, Ki67 fraction classified as either less than or greater than 10% within the in situ component of lung adenocarcinoma was identified as a strong predictor of patient outcome. This supports the proposition that tumors of all stages that have 'high grade' in situ components represent those with aggressive lepidic growth of the invasive clone. Overall these data support that the combined growth of Noguchi C tumors can represent two differing biological states and that 'Noguchi C1' tumors represent the genuine biological shift from in situ to invasive disease.

Low Expression of Pseudogene POU5F1B Affects Diagnosis and Prognosis in Acute Myeloid Leukemia (AML).

BACKGROUND The transcription factor Oct-4 is necessary for maintaining pluripotency and self-renewal of embryonic stem cells, and POU5F1B is a processed pseudogene of Oct-4 with coding capacity. The purpose of this study is to evaluate the expression and clinical implication of POU5F1B in AML. MATERIAL AND METHODS The expression of the POU5F1B transcript was evaluated in 175 newly diagnosed AML patients and 39 healthy controls by use of real-time quantitative PCR (RQ-PCR). RESULTS POU5F1B was underexpressed in AML compared with controls (P<0.001). The receiver operating characteristic (ROC) curve revealed that the POU5F1B transcript level was able to differentiate AML patients from healthy individuals (AUC=0.682). In non-APL AML patients, the POU5F1Blow group had significantly higher WBC than the POU5F1Bhigh group (20.2×109 vs. 4.6×109 L⁻¹, P=0.021). Among whole-cohort AML, non-APL AML, and intermediate-risk AML, POU5F1Bhigh patients had obviously higher complete remission (CR) rates than POU5F1Blow patients (P=0.012, P=0.012 and P=0.027). In addition, Kaplan-Meier analysis demonstrated better overall survival (OS, P=0.019, P=0.007 and P=0.046, respectively) in POU5F1Bhigh patients compared with POU5F1Blow patients. Furthermore, in multivariate survival analysis, POU5F1B was independently associated with OS in non-APL AML patients and intermediate-risk AML as a favorable prognostic factor. CONCLUSIONS POU5F1B was frequently underexpressed in AML, and might contribute to the diagnosis and prognosis of AML.

Ultrahigh pressure filtration dewatering of municipal sludge based on microwave pretreatment.

Municipal sludge is difficult to treat and dispose of because of its high moisture content (MC) and volume. In this study, a novel dewatering method that utilizes ultrahigh pressure filtration (UHPF) and thin-cake-press (TCP) coupled with microwave pretreatment was proposed to reduce the MC of sludge cake. The influence of microwave contact time (MCT), microwave intensity (MI), initial MC of sludge, dewatering time, applied pressure and sludge weight (Ws) on the MC of a sludge cake was investigated by the single-factor experiment. Moreover, a water discharge path model was developed to understand the dewatering mechanism and explain the relationship between thickness and MC of the cake. The key factors affecting the MC of the cake were explored by the orthogonal experiment. The experimental results showed that microwave irradiation could effectively improve the dewatering performance and reduce the MC of the sludge cake. The MC of the cake reached its lowest value of 28% at MCT of 120 s and MI of 400 W, which is much lower than the value obtained by the traditional dewatering method. Among the parameters mentioned above, Ws has the most significant influence on MC because a large amount of sludge leads to a thicker cake, which seriously hampers the flow of filtrate and inevitably increases the MC of the cake.

99m Tc-labeled oligomeric nanoparticles as potential agents for folate receptor-positive tumor targeting.

One type of biocompatible nanoparticles functionalized with folate and 99m Tc was successfully synthesized. Maleimide-folic acid (Mal-FA) was selected to covalently conjugate with -SH of the nanoparticles (NPs) to prepare NPs-FA for targeting. 99m Tc was selected to conjugate with -NH2 and -SH groups of cysteine residues on the surface of NPs to prepare NPs-FA-99m Tc for radioactive counting. The ability to target folate receptors of NPs-FA-99m Tc was assessed in uptake studies with folate-receptor-positive human HepG2 cells. The results showed that the as-prepared NPs can selectively uptake by folate receptor-overexpressing HepG2 tumor cells in vitro. The oligomeric hybrid NPs radiolabeled with 99m Tc may develop to be SPECT/CT imaging biomaterials with high selectivity.

Characteristics of whole-body dynamic 18F-FDG PET/CT Patlak multi-parametric imaging in lung cancer and the influence of different delineation methods on quantitative parameters.

Background: Dynamic course of flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) Patlak muti-parametric imaging spatial distribution in the targeted tissues may reveal highly useful clinical information about the tissue's metabolic properties. The characteristics of the Patlak multi-parametric imaging in lung cancer and the influence of different delineation methods on quantitative parameters may provide reference for the clinical application of this new technology. Methods: A total of 27 patients with pathologically diagnosed lung cancer underwent whole-body dynamic 18F-FDG PET/CT examination before treatment. Parametric images of metabolic rate of FDG (MRFDG) and Patlak intercept (or distribution volume; DV) were generated using Patlak reconstruction. The values of primary lung cancer lesions, target-to-background ratio (TBR), and contrast-to-noise ratio (CNR) were investigated using contour delineation and boundary delineation. Statistical analysis was performed to analyze the relationship between multi-parametric images and clinicopathological features, and to compare the effects of contour delineation and boundary delineation on quantitative parameters. Results: MRFDG images showed higher TBR and CNR than did standardized uptake value (SUV) images. There were significant differences in MRFDG-max, MRFDG-mean, and MRFDG-peak among groups with different tumor diameters and pathology types (P<0.05). Moreover, the metabolic parameters of MRFDG were higher in patients with tumor diameters ≥3 cm and squamous carcinoma. The differences of the maximum and peak values of MRFDG and DV were not statistically significant in the different outlining method subgroups (all P>0.05). However, the difference of the mean values of MRFDG and DV were statistically significant in the different outline method groupings (all P<0.05). Conclusions: Dynamic 18F-FDG PET/CT Patlak multi-parametric imaging can obtain quantitative values for lung cancer with high TBR and CNR. Moreover, the multi-parameters are various from different pathology types to tumor size. Different delineation methods have a greater influence on the mean value of quantitative parameters.