pH-Triggered Transformable Peptide Nanocarriers Extend Drug Retention for Breast Cancer Combination Therapy.

Increasing the penetration and accumulation of antitumor drugs at the tumor site are crucial in chemotherapy. Smaller drug-loaded nanoparticles (NPs) typically exhibit increased tumor penetration and more effective permeation through the nuclear membrane, whereas larger drug-loaded NPs show extended retention at the tumor site. In addition, cancer stem cells (CSCs) have unlimited proliferative potential and are crucial for the onset, progression, and metastasis of cancer. Therefore, a drug-loaded amphiphilic peptide, DDP- and ATRA-loaded Pep1 (DA/Pep1), is designed that self-assembles into spherical NPs upon the encapsulation of cis-diamminedichloroplatinum (DDP) and all-trans retinoic acid (ATRA). In an acidic environment, DA/Pep1 transforms into aggregates containing sheet-like structures, which significantly increases drug accumulation at the tumor site, thereby increasing antitumor effects and inhibiting metastasis. Moreover, although DDP treatment can increase the number of CSCs present, ATRA can induce the differentiation of CSCs in breast cancer to increase the therapeutic effect of DDP. In conclusion, this peptide nanodelivery system that transforms in response to the acidic tumor microenvironment is an extremely promising nanoplatform that suggests a new idea for the combined treatment of tumors.

The enhancement of energy supply in syngas-fermenting microorganisms.

After the second industrial revolution, social productivity developed rapidly, and the use of fossil fuels such as coal, oil, and natural gas increased greatly in industrial production. The burning of these fossil fuels releases large amounts of greenhouse gases such as CO2, which has caused greenhouse effects and global warming. This has endangered the planet's ecological balance and brought many species, including animals and plants, to the brink of extinction. Thus, it is crucial to address this problem urgently. One potential solution is the use of syngas fermentation with microbial cell factories. This process can produce chemicals beneficial to humans, such as ethanol as a fuel while consuming large quantities of harmful gases, CO and CO2. However, syngas-fermenting microorganisms often face a metabolic energy deficit, resulting in slow cell growth, metabolic disorders, and low product yields. This problem limits the large-scale industrial application of engineered microorganisms. Therefore, it is imperative to address the energy barriers of these microorganisms. This paper provides an overview of the current research progress in addressing energy barriers in bacteria, including the efficient capture of external energy and the regulation of internal energy metabolic flow. Capturing external energy involves summarizing studies on overexpressing natural photosystems and constructing semiartificial photosynthesis systems using photocatalysts. The regulation of internal energy metabolic flows involves two parts: regulating enzymes and metabolic pathways. Finally, the article discusses current challenges and future perspectives, with a focus on achieving both sustainability and profitability in an economical and energy-efficient manner. These advancements can provide a necessary force for the large-scale industrial application of syngas fermentation microbial cell factories.

Tetrahedral framework nucleic acids-based delivery of MicroRNA-22 inhibits pathological neovascularization and vaso-obliteration by regulating the Wnt pathway.

The objective of this study was to investigate the effects and molecular mechanisms of tetrahedral framework nucleic acids-microRNA22 (tFNAs-miR22) on inhibiting pathological retinal neovascularization (RNV) and restoring physiological retinal vessels. A novel DNA nanocomplex (tFNAs-miR22) was synthesised by modifying microRNA-22 (miR22) through attachment onto tetrahedral frame nucleic acids (tFNAs), which possess diverse biological functions. Cell proliferation, wound healing, and tube formation were employed for in vitro assays to investigate the angiogenic function of cells. Oxygen-induced retinopathy (OIR) model was utilised to examine the effects of reducing pathological neovascularization (RNV) and inhibiting vascular occlusion in vivo. In vitro, tFNAs-miR22 demonstrated the ability to penetrate endothelial cells and effectively suppress cell proliferation, tube formation, and migration in a hypoxic environment. In vivo, tFNAs-miR22 exhibited promising results in reducing RNV and promoting the restoration of normal retinal blood vessels in OIR model through modulation of the Wnt pathway. This study provided a theoretical basis for the further understanding of RNV, and highlighted the innovative and potential of tFNAs-miR22 as a therapeutic option for ischemic retinal diseases.

Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer.

Rationale: Multiple copies in T-cell malignancy 1 (MCT-1) is a prognostic biomarker for aggressive breast cancers. Overexpressed MCT-1 stimulates the IL-6/IL-6R/gp130/STAT3 axis, which promotes epithelial-to-mesenchymal transition and cancer stemness. Because cancer stemness largely contributes to the tumor metastasis and recurrence, we aimed to identify whether the blockade of MCT-1 and IL-6R can render these effects and to understand the underlying mechanisms that govern the process. Methods: We assessed primary tumor invasion, postsurgical local recurrence and distant metastasis in orthotopic syngeneic mice given the indicated immunotherapy and MCT-1 silencing (shMCT-1). Results: We found that shMCT-1 suppresses the transcriptomes of the inflammatory response and metastatic signaling in TNBC cells and inhibits tumor recurrence, metastasis and mortality in xenograft mice. IL-6R immunotherapy and shMCT-1 combined further decreased intratumoral M2 macrophages and T regulatory cells (Tregs) and avoided postsurgical TNBC expansion. shMCT-1 also enhances IL-6R-based immunotherapy effectively in preventing postsurgical TNBC metastasis, recurrence and mortality. Anti-IL-6R improved helper T, cytotoxic T and natural killer (NK) cells in the lymphatic system and decreased Tregs in the recurrent and metastatic tumors. Combined IL-6R and PD-L1 immunotherapies abridged TNBC cell stemness and M2 macrophage activity to a greater extent than monotherapy. Sequential immunotherapy of PD-L1 and IL-6R demonstrated the best survival outcome and lowest postoperative recurrence and metastasis compared with synchronized therapy, particularly in the shMCT-1 context. Multiple positive feedforward loops of the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 axis were identified in TNBC cells, which boosted metastatic niches and immunosuppressive microenvironments. Clinically, MCT-1high/PD-L1high/CXCL7high and CXCL7high/IL-6high/IL-6Rhigh expression patterns predict worse prognosis and poorer survival of breast cancer patients. Conclusion: Systemic targeting the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 interconnections enhances immune surveillance that inhibits the aggressiveness of TNBC.

Unveiling the Regulatory Role of miRNAs in Internode Elongation: Integrated Analysis of MicroRNA and mRNA Expression Profiles across Diverse Dwarfing Treatments in Maize (Zea mays L.).

MicroRNAs are crucial regulators of gene expression in maize. However, the mechanisms through which miRNAs control internode elongation remain poorly understood. This study engineered varying levels of internode elongation inhibition, revealing that dwarfing treatments diminished gibberellin levels, curtailed cell longitudinal growth, and slowed the rate of internode elongation. Comprehensive transcriptome and miRNA profiling of the internode elongation zone showed gene expression changes that paralleled the extent of the internode length reduction. We identified 543 genes and 29 miRNAs with significant correlations to internode length, predominantly within families, including miR164 and miR396. By incorporating target gene expression levels, we pinpointed nine miRNA-mRNA pairs that are significantly associated with the regulation of the internode elongation. The inhibitory effects of these miRNAs on their target genes were confirmed through dual-luciferase reporter assays. Overexpression of miR164h in maize resulted in increased internode and cell length, suggesting a novel genetic avenue for manipulating plant stature. These miRNAs may also serve as precise spatiotemporal regulators for in vitro plant development.

Measuring entanglement entropy and its topological signature for phononic systems.

Entanglement entropy is a fundamental concept with rising importance in various fields ranging from quantum information science, black holes to materials science. In complex materials and systems, entanglement entropy provides insight into the collective degrees of freedom that underlie the systems' complex behaviours. As well-known predictions, the entanglement entropy exhibits area laws for systems with gapped excitations, whereas it follows the Gioev-Klich-Widom scaling law in gapless fermion systems. However, many of these fundamental predictions have not yet been confirmed in experiments due to the difficulties in measuring entanglement entropy in physical systems. Here, we report the experimental verification of the above predictions by probing the nonlocal correlations in phononic systems. We obtain the entanglement entropy and entanglement spectrum for phononic systems with the fermion filling analog. With these measurements, we verify the Gioev-Klich-Widom scaling law. We further observe the salient signatures of topological phases in entanglement entropy and entanglement spectrum.

Design, synthesis and evaluation of C-5 substituted pyrrolopyridine derivatives as potent Janus Kinase 1 inhibitors with excellent selectivity.

The development of highly selective Janus Kinase 1 (JAK1) inhibitors is crucial for improving efficacy and minimizing adverse effects in the clinical treatment of autoimmune diseases. In a prior study, we designed a series of C-5 4-pyrazol substituted pyrrolopyridine derivatives that demonstrated significant potency against JAK1, with a 10 âˆ¼ 20-fold selectivity over Janus Kinase 2 (JAK2). Building on this foundation, we adopted orthogonal strategy by modifying the C-5 position with 3-pyrazol/4-pyrazol/3-pyrrol groups and tail with substituted benzyl groups on the pyrrolopyridine head to enhance both potency and selectivity. In this endeavor, we have identified several compounds that exhibit excellent potency and selectivity for JAK1. Notably, compounds 12b and 12e, which combined 4-pyrazol group at C-5 site and meta-substituted benzyl tails, displayed IC50 value with 2.4/2.2 nM and high 352-/253-fold selectivity for JAK1 over JAK2 in enzyme assays. Additionally, both compounds showed good JAK1-selective in Ba/F3-TEL-JAK1/2 cell-based assays. These findings mark a substantial improvement, as these compounds are 10-fold more potent and over 10-fold more selective than the best compound identified in our previous study. The noteworthy potency and selectivity properties of compounds 12b and 12e suggest their potential utility in furthering the development of drugs for autoimmune diseases.

3D reconstruction of the uterus and automatic segmentation of the uterine cavity on 3D magnetic resonance imaging: A preliminary study.

Purpose: To determine the differences in 3D shape features between septate uterus (SU) and normal uterus and to train a network to automatically delineate uterine cavity on 3D magnetic resonance imaging (MRI). Methods: A total of 43 patients (22 cases of partial septate uterus and 21 cases of complete septate uterus) were included in the experimental group. Nine volunteers were recruited as a control group. The uterine cavity (UC), myometrium (UM), and cervical canal of the uterus were segmented manually using ITK-SNAP software. The three-dimensional shape features of the UC and UM were extracted by using PyRadiomics. The recurrent saliency transformation network (RSTN) method was used to segment the UC. Results: The values of four 3D shape features were significantly lower in the control group than in the partial septate group and the complete septate group, while the values of two features were significantly higher (p < 0.05). The UCs of the three groups were significantly different in terms of flatness and sphericity. The values of six features were significantly lower in the UMs of the control group than in those of the partial septate group and the complete septate group (p < 0.05). After the deep learning networks were trained, the Dice similarity coefficient (DSC) scores of the four folds for different thresholds were all over 80 %. The average volume ratio between predictions and manual segmentation was 101.2 %. Conclusions: Based on 3D reconstruction, 3D shape features can be used to comprehensively evaluate septate uterus and provide a reference for subsequent research. The UC can be automatically segmented on 3D MRI using the RSTN method.

ZmNRT1.1B (ZmNPF6.6) determines nitrogen use efficiency via regulation of nitrate transport and signalling in maize.

Nitrate (NO3 - ) is crucial for optimal plant growth and development and often limits crop productivity under low availability. In comparison with model plant Arabidopsis, the molecular mechanisms underlying NO3 - acquisition and utilization remain largely unclear in maize. In particular, only a few genes have been exploited to improve nitrogen use efficiency (NUE). Here, we demonstrated that NO3 - -inducible ZmNRT1.1B (ZmNPF6.6) positively regulated NO3 - -dependent growth and NUE in maize. We showed that the tandem duplicated proteoform ZmNRT1.1C is irrelevant to maize seedling growth under NO3 - supply; however, the loss of function of ZmNRT1.1B significantly weakened plant growth under adequate NO3 - supply under both hydroponic and field conditions. The 15 N-labelled NO3 - absorption assay indicated that ZmNRT1.1B mediated the high-affinity NO3 - -transport and root-to-shoot NO3 - translocation. Transcriptome analysis further showed, upon NO3 - supply, ZmNRT1.1B promotes cytoplasmic-to-nuclear shuttling of ZmNLP3.1 (ZmNLP8), which co-regulates the expression of genes involved in NO3 - response, cytokinin biosynthesis and carbon metabolism. Remarkably, overexpression of ZmNRT1.1B in modern maize hybrids improved grain yield under N-limiting fields. Taken together, our study revealed a crucial role of ZmNRT1.1B in high-affinity NO3 - transport and signalling and offers valuable genetic resource for breeding N use efficient high-yield cultivars.

Analysis of Cadmium Contamination in Lettuce (Lactuca sativa L.) Using Visible-Near Infrared Reflectance Spectroscopy.

In order to rapidly and accurately monitor cadmium contamination in lettuce and understand the growth conditions of lettuce under cadmium pollution, lettuce is used as the test material. Under different concentrations of cadmium stress and at different growth stages, relative chlorophyll content of lettuce leaves, the cadmium content in the leaves, and the visible-near infrared reflectance spectra are detected and analyzed. An inversion model of the cadmium content and relative chlorophyll content in the lettuce leaves is established. The results indicate that cadmium concentrations of 1 mg/kg and 5 mg/kg promote relative chlorophyll content, while concentrations of 10 mg/kg and 20 mg/kg inhibit relative chlorophyll content. The cadmium content in the leaves increases with increasing cadmium concentrations. Cadmium stress caused a "blue shift" in the red edge position only during the mature period, while the red valley position underwent a "blue shift" during the seedling and growth periods and a "red shift" during the mature period. The green peak position exhibited a "blue shift". After model validation, it was found that the model constructed using the ratio of red edge area to yellow edge area and the normalized values of red edge area and yellow edge area effectively estimated the cadmium content in lettuce leaves. The model established using the normalized vegetation index of the red edge and the ratio of the peak green value to red shoulder amplitude can effectively estimate the relative chlorophyll content in lettuce leaves. This study demonstrates that the visible-near infrared spectroscopy technique holds great potential for monitoring cadmium contamination and estimating chlorophyll content in lettuce.

Application of a diagnosis flow draft based on appearance impression for detection of vulvar disease.

OBJECTIVES: The aims of this retrospective study were to evaluate the clinical applicability of the latest International Society for the Study of Vulvovaginal Disease (ISSVD) and International Federation for Cervical Pathology and Colposcopy (IFCPC) terminology for vulvar diseases, and to explore a new evaluation flow to optimize decision-making on diagnosis. METHODS: 1,068 patients with 5,340 qualified vulvar images were evaluated by observers using 2011 ISSVD and 2011 IFCPC terminology systems. The sensitivity, specificity, positive predictive value, negative predictive value, Youden Index and Overall Diagnostic Value (ODV) were calculated for each finding in the two systems. Then the disease diagnosis order and a diagnosis flow draft (DFD) were obtained. RESULTS: A total of 15 kinds of vulvar diseases were diagnosed. The proportion of patients accompanied with cervical or vaginal intraepithelial neoplasia was highest (83.3 %) in vulvar Paget's disease group (p<0.001). Total area of lesions was larger in vulvar Paget's disease, lichen simplex chronicus and lichen sclerosus group (p<0.001). Among the top five findings of ODV, some findings inferred several (≥6) kinds of diseases, while some findings only exist in a certain disease. When the DFD was used, the agreement between the initial impression and histopathology diagnosis was 68.8 %, higher than those when ISSVD an IFCPC terminology systems used (p=0.028), and it didn't change with the experience of the observer (p=0.178). CONCLUSIONS: Based on the findings in ISSVD and IFCPC terminology systems, we explored a DFD for observers with different experience on the detection of vulvar disease.

Assessment of key parameters of normal uterus in women of reproductive age.

Currently, the precise and detailed anatomical data of the normal uterus, especially the myometrium thickness in various parts of the uterus, are lacking. This study aims to provide normal references for uterine size in healthy reproductive-aged Chinese women to facilitate the application of hysteroscopic surgery. A total of 298 women of reproductive age with normal uterine were included. Parity was significantly correlated with uterine measurements (P < 0.05), and age impacted several measurements (P < 0.05). At each uterine site examined, the myometrium was thinner in nulliparous women than in parous or primiparous women (P < 0.001). Similarly, the extrauterine measurements for parous or primiparous women were larger than those for nulliparous women. Weight affected some external measurements but not myometrial thicknesses, while height did not affect uterine measurements (P > 0.05). There was a positive correlation between body mass index (BMI) and extrauterine measurements as well as myometrial thickness (P < 0.05). The mathematical model of the uterine size for women of reproductive age was constructed stratified by parity. The study is the first to provide a detailed statistical description of the accurate anatomical parameters of the uterus in Chinese reproductive-aged women and has great significance for improving the safety and effectiveness of hysteroscopic surgery for patients.

Meta-pharmacokinetic analysis of posaconazole following dosing of oral suspension, delayed-release tablet, and intravenous infusion in patients vs. healthy volunteers: Impact of clinical characteristics and race.

OBJECTIVES: To investigate the potential impact of clinical characteristics and the Chinese race on posaconazole pharmacokinetics in patients using an integrated population pharmacokinetic model for posaconazole oral suspension (SUS), delayed-release tablet (DR-tablet), and intravenous (IV) infusion that was developed in healthy volunteers (HV). METHODS: 1046 concentrations from 105 prospectively studied Caucasian patients receiving either of the three posaconazole formulations were pooled with 3898 concentrations from 182 HV. Clinical characteristics were tested for significance. The impact of Chinese race was assessed using 292 opportunistic samples from 80 Chinese patients receiving SUS. RESULTS: Bioavailability of SUS (Fsus) in patients decreased from 38.2% to 24.6% when the dose was increased from 100 mg to 600 mg. Bioavailability of DR-tablet (Ftab) was 59% regardless of dose. Mucositis, diarrhoea, administration through a nasogastric tube, and concomitant use of proton pump inhibitors or metoclopramide reduced Fsus by 61%, 36%, 44%, 48%, and 29%, respectively, putting patients with these characteristics at increased risk of inadequate exposure. Clearance decreased from 7.0 to 5.1 L/h once albumin levels were <30 g/L. Patients showed an 84.4% larger peripheral volume of distribution (Vp) and 67.5% lower intercompartmental clearance (Q) compared with HV. No racial difference could be identified. CONCLUSIONS: Pharmacokinetics of posaconazole in patients differ considerably to those in HV, with altered Fsus that is also impacted by clinical covariates, an Ftab similar to fasted conditions in HV, and altered parameters for clearance, Vp, and Q. There was no evidence to indicate that Chinese patients require a different dose to Caucasian patients.

Overcoming the Miscibility Gap of GaN/InN in MBE Growth of Cubic InxGa1-xN.

The lack of internal polarization fields in cubic group-III nitrides makes them promising arsenic-free contenders for next-generation high-performance electronic and optoelectronic applications. In particular, cubic InxGa1-xN semiconductor alloys promise band gap tuning across and beyond the visible spectrum, from the near-ultraviolet to the near-infrared. However, realization across the complete composition range has been deemed impossible due to a miscibility gap corresponding to the amber spectral range. In this study, we use plasma-assisted molecular beam epitaxy (PAMBE) to fabricate cubic InxGa1-xN films on c-GaN/AlN/3C-SiC/Si template substrates that overcome this challenge by careful adjustment of the growth conditions, conclusively closing the miscibility gap. X-ray diffraction reveals the composition, phase purity, and strain properties of the InxGa1-xN films. Scanning transmission electron microscopy reveals a CuPt-type ordering on the atomistic scale in highly alloyed films with x(In) ≈ 0.5. Layers with much lower and much higher indium content exhibit statistical distributions of the cations Ga and In. Notably, this CuPt-type ordering results in a spectrally narrower emission compared to that of statistically disordered zincblende materials. The emission energies of the films range from 3.24 to 0.69 eV and feature a quadratic bowing parameter of b = 2.4 eV. In contrast, the LO-like phonon modes that are observed by Raman spectroscopy exhibit a one-mode behavior and shift linearly from c-GaN to c-InN.

Exosome-Mediated Activation of the Prostasin-Matriptase Serine Protease Cascade in B Lymphoma Cells.

Prostasin and matriptase are extracellular membrane serine proteases with opposing effects in solid epithelial tumors. Matriptase is an oncoprotein that promotes tumor initiation and progression, and prostasin is a tumor suppressor that reduces tumor invasion and metastasis. Previous studies have shown that a subgroup of Burkitt lymphoma have high levels of ectopic matriptase expression but no prostasin. Reducing the matriptase level via small interfering RNAs in B lymphoma cells impeded tumor xenograft growth in mice. Here, we report a novel approach to matriptase regulation in B cancer cells by prostasin via exosomes to initiate a prostasin-matriptase protease activation cascade. The activation and shedding of matriptase were monitored by measuring its quantity and trypsin-like serine protease activity in conditioned media. Sustained activation of the protease cascade in the cells was achieved by the stable expression of prostasin. The B cancer cells with prostasin expression presented phenotypes consistent with its tumor suppressor role, such as reduced growth and increased apoptosis. Prostasin exosomes could be developed as an agent to initiate the prostasin-matriptase cascade for treating B lymphoma with further studies in animal models.

Anthocyanin and proanthocyanidin from Aronia melanocarpa (Michx.) Ell.: Purification, fractionation, and enzyme inhibition.

Aronia melanocarpa (Michx.) Ell. is a rich source of anthocyanins and proanthocyanidins with confirmed health benefits. Individual cyanidin glucosides (cyanidin 3-galactoside, cyanidin 3-arabinoside, cyanidin 3-xyloside, and cyanidin 3-glucoside) of anthocyanins (calculated by individual cyanin glycoside fractions was 419.9 mg/100 g FW) were isolated by Sephadex LH-20 column and different parts of proanthocyanidins with a different mean degree of polymerization (mDP) were fractionated by the solubility differences in different solvents. The composition of different mDP of proanthocyanidins was as follows: monomers (1.51%), oligomer (mDP of 4.2 ± 0.9, 20.57%), CPP-50 (mDP of 78.9 ± 4.1, 22.17%), CPP-60 (mDP of 66.1 ± 1.2, 27.94%), CPP-70 (mDP of 36.8 ± 3.9, 36.8%), CPP-75 (mDP of 25.2 ± 1.3, 6.14%), CPP-L (mDP of 10.2 ± 2.6, 6.95%), and there were recycling loss of 0.34%. Cyanidin 3-glucoside showed the strongest inhibition effects on α-amylase and lipase and cyanidin 3-arabinoside showed the strongest inhibition effect on α-glucosidase, while cyanidin 3-xyloside has no inhibition effect on the α-amylase, and cyanidin 3-galactoside, cyanidin 3-arabinoside, and cyanidin 3-xyloside have no inhibition effects on lipase. The inhibition effect of proanthocyanidins with different mDP to the enzymes all showed high negative correlations between the mDP and IC50 (half-maximal inhibitory concentration). This study suggests that A. melanocarpa (Michx.) Ell. can have beneficial effects due to inhibition of the digestion enzyme.

Genetic and lipidomic analyses reveal the key role of lipid metabolism for cold tolerance in maize.

Lipid remodeling is crucial for cold tolerance in plants. However, the precise alternations of lipidomics during cold responses remain elusive, especially in maize (Zea mays L.). In addition, the key genes responsible for cold tolerance in maize lipid metabolism have not been identified. Here, we integrate lipidomic, transcriptomic, and genetic analysis to determine the profile of lipid remodeling caused by cold stress. We find that the homeostasis of cellular lipid metabolism is essential for maintaining cold tolerance of maize. Also, we detect 213 lipid species belonging to 14 major classes, covering phospholipids, glycerides, glycolipids, and free fatty acids. Various lipid metabolites undergo specific and selective alterations in response to cold stress, especially mono-/di-unsaturated lysophosphatidic acid, lysophosphatidylcholine, phosphatidylcholine, and phosphatidylinositol, as well as polyunsaturated phosphatidic acid, monogalactosyldiacylglycerol, diacylglycerol, and triacylglycerol. In addition, we identify a subset of key enzymes, including ketoacyl-acyl-carrier protein synthase II (KAS II), acyl-carrier protein 2 (ACP2), male sterility33 (Ms33), and stearoyl-acyl-carrier protein desaturase 2 (SAD2) involved in glycerolipid biosynthetic pathways are positive regulators of maize cold tolerance. These results reveal a comprehensive lipidomic profile during the cold response of maize and provide genetic resources for enhancing cold tolerance in crops.

Association between CZT­SPECT myocardial blood flow and coronary stenosis: A cross­sectional study.

The association between the quantitative and semi-quantitative parameters of myocardial blood flow obtained using cadmium-zinc-telluride single photon emission computed tomography (CZT-SPECT) and coronary stenosis remains unclear. Therefore, the objective of the present study was to evaluate the diagnostic value of two parameters obtained using CZT-SPECT in patients with suspected or known coronary artery disease. A total of 24 consecutive patients who underwent CZT-SPECT and coronary angiography within 3 months of each other were included in the study. To evaluate the predictive ability of the regional difference score (DS), coronary flow reserve (CFR), and the combination thereof for positive coronary stenosis at the vascular level, receiver operating characteristic (ROC) curves were plotted and the area under the curves (AUCs) were calculated. Comparisons of the reclassification ability for coronary stenosis between different parameters were assessed by calculating the net reclassification index (NRI) and the integrated discrimination improvement (IDI). The 24 participants (median age: 65 years; range: 46-79 years; 79.2% male) included in this study had a total of 72 major coronary arteries. When stenosis ≥50% was defined as the criteria for positive coronary stenosis, the AUCs and the 95% confidence interval (CI) for regional DS, CFR, and the combination of the two indices were 0.653 (CI, 0.541-0.766), 0.731 (CI, 0.610-0.852) and 0.757 (CI, 0.645-0.869), respectively. Compared with single DS, the combination of DS and CFR increased the predictive ability for positive stenosis, with an NRI of 0.197-1.060 (P<0.01) and an IDI of 0.0150-0.1391 (P<0.05). When stenosis ≥75% was considered as the criteria, the AUCs were 0.760 (CI, 0.614-0.906), 0.703 (CI, 0.550-0.855), and 0.811 (CI, 0.676-0.947), respectively. Compared with DS, CFR had an IDI of -0.3392 to -02860 (P<0.05) and the combination of DS and CFR also enhanced the predictive ability, with an NRI of 0.0313-1.0758 (P<0.01). In conclusion, both regional DS and CFR had diagnostic values for coronary stenosis, but the diagnostic abilities differed in distinguishing between different degrees of stenosis, and the efficiency was improved with a combination of DS and CFR.

Occurrence and multi-pathway health risk assessment of trihalomethanes in drinking water of Wuxi, China.

Chlorination is widely used to disinfect drinking water to keep humans safe from microorganisms. During chlorination, chlorine and its compounds react with contaminants to form disinfection by-products (DBPs). Toxicological and epidemiological studies have demonstrated that trihalomethanes (THMs) are the most widely investigated DBPs in drinking water, and their exposure has been associated with some adverse health effects. However, studies about risk characteristics in this field are limited. We estimated the health risks of THMs exposure in drinking water through multi-pathways, and systematically analyzed the factors influencing health risks of THMs in Wuxi, China. A total of 488 drinking water samples were collected and analyzed for THMs from four water treatment utilities from 2008 to 2016 in Wuxi. And water exposure parameters were obtained from 602 participants by structured questionnaires. The median concentration of THMs ranged from 6.71 µg/L to 9.18 µg/L. The cumulative cancer risk of THMs exposure through multi-pathways was 1.26 × 10-4, and CHBr2Cl made the largest contribution to the total cancer risk (48.25%). The non-cancer risk of THMs exposure was 2.02 × 10-1. Health risks of the exposure to THMs in drinking water in summer were significantly higher than that in winter (P = 0.0003 for cancer risk, and P = 5.95 × 10-7 for non-cancer risk). In our study, the average individual disability-adjusted life years (DALYs) lost was 1.27 × 10-4 per person-year (ppy). This study attempted to use DALYs for risk assessment of THMs, which will provide useful information for risk comparison and prioritization of hazards in drinking water. This suggested that potential higher risk might exist, and possible measures could be considered to decrease the health risks.