Microbial community succession and responses to internal environmental drivers throughout the operation of constructed wetlands.

Constructed wetlands (CWs) have been widely used to ensure effective domestic wastewater treatment. Microorganisms-derived CWs have received extensive attention as they play a crucial role. However, research on the succession patterns of microbial communities and the influencing mechanisms of internal environmental factors throughout entire CW operations remains limited. In this context, three parallel-operated CWs were established in this study to assess the microbial communities and their influencing environmental factors at different substrate depths throughout the operation process using 16S rRNA gene high-throughput sequencing and metagenomic sequencing. The results showed gradual reproduction and accumulation of the microbial communities throughout the CW operation. Although gradual increases in the richness and diversity of the microbial communities were found, there were decreases in the functional expression of the dominant microbial species. The excessive accumulation of microorganisms will decrease the oxidation-reduction potential (ORP) within CWs and attenuate their influence on effluent.. Dissolved oxygen (DO) was the major factor influencing the microbial community succession over the CW operation. The main identified functional bacterial genera responsible for the ammonium oxidation, nitrification, and denitrification processes in the CWs were Nitrosospira, Nitrobacter, Nitrospira, Rhodanobacter, and Nakamurella. The narG gene was identified as a key functional gene linking various components of nitrogen cycling, while pH, electrical conductivity (EC), and ORP were the major environmental factors affecting the metabolism characteristics of nitrogen functional microorganisms. This study provides a theoretical basis for the effective regulation of related microbial communities to achieve long-term, efficient, and stable CW operations.

Dissection of transcriptome dysregulation and immune characterization in women with germline BRCA1 mutation at single-cell resolution.

BACKGROUND: High-grade serous carcinoma (HGSC) is the most frequent and lethal type of ovarian cancer. It has been proposed that tubal secretory cells are the origin of ovarian HGSC in women with familial BRCA1/2 mutations. However, the molecular changes underlying malignant transformation remain unknown. METHOD: We performed single-cell RNA and T cell receptor sequencing of tubal fimbriated ends from 3 BRCA1 germline mutation carriers (BRCA1 carriers) and 3 normal controls with no high-risk history (non-BRCA1 carriers). RESULTS: Exploring the transcriptomes of 19,008 cells, predominantly from BRCA1+ samples, we identified 5 major cell populations in the fallopian tubal mucosae. The secretory cells of BRCA1+ samples had differentially expressed genes involved in tumor growth and regulation, chemokine signaling, and antigen presentation compared to the wild-type BRCA1 controls. There are several novel findings in this study. First, a subset of the fallopian tubal secretory cells from one BRCA1 carrier exhibited an epithelial-to-mesenchymal transition (EMT) phenotype, which was also present in the mucosal fibroblasts. Second, we identified a previously unreported phenotypic split of the EMT secretory cells with distinct evolutionary endpoints. Third, we observed increased clonal expansion among the CD8+ T cell population from BRCA1+ carriers. Among those clonally expanded CD8+ T cells, PD-1 was significantly increased in tubal mucosae of BRCA1+ patients compared with that of normal controls, indicating that T cell exhaustion may occur before the development of any premalignant or malignant lesions. CONCLUSION: These results indicate that EMT and immune evasion in normal-looking tubal mucosae may represent early events leading to the development of HGSC in women with BRCA1 germline mutation. Our findings provide a probable molecular mechanism explaining why some, but not all, women with BRCA1 germline mutation present with early development and rapid dissemination of HGSC.

Construction of TiO2(B)/Anatase Heterophase Junctions via a Water-Induced Phase Transformation Strategy for Enhanced Photocatalytic Hydrogen Production.

The development of facile and green solution-phase routes toward the fabrication of TiO2-based heterophase junctions with a delicate control of phase and structure is a challenging task. Herein, we report a simple and convenient method to controllably fabricate TiO2(B)/anatase heterophase junctions, which was successfully realized by utilizing the ideal great solvent of water to treat the presynthesized TiO2(B) nanosheet precursor at a low temperature of 80 °C. On the basis of phase structure transformation and morphology evolution data, the formation of these TiO2(B)/anatase heterophase junctions was reasonably explained by a novel water-induced TiO2(B) → anatase phase transformation mechanism. Benefiting from the desirable structural and photoelectronic advantages of more exposed active sites, enhanced light absorbance, and promoted separation of photogenerated electron-hole pairs, the thus-transformed TiO2(B)/anatase heterophase junctions exhibit fascinating photocatalytic performance in water splitting. Specifically, with the help of Pt as a cocatalyst and methanol as a sacrificial agent, the H2 production rate of optimized TiO2(B)/anatase heterophase junction reaches 6.92 mmol·g-1·h-1, which is almost 7.1 and 2.1 times higher than those of the pristine TiO2(B) nanosheets and the final anatase nanocrystals. More interestingly, the TiO2(B)/anatase heterophase junction also delivers prominent activity toward pure water splitting to simultaneously produce H2 and H2O2, with evolution rates of up to 1.10 and 0.55 mmol·g-1·h-1, respectively. Our work may advance the facile green solvent-mediated synthesis of metal oxide-based heterophase junctions for applications in energy- and environmental-related areas.

Association of Early and Late Contrast-Associated Acute Kidney Injury and Long-Term Mortality in Patients Undergoing Coronary Angiography.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a common complication in patients undergoing coronary angiography (CAG). However, few studies demonstrate the association between the prognosis and developed CA-AKI in the different periods after the operation. METHODS: We retrospectively enrolled 3206 patients with preoperative serum creatinine (Scr) and at least twice SCr measurement after CAG. CA-AKI was defined as an increase ≥50% or ≥0.3 mg/dL from baseline in the 72 hours after the procedure. Early CA-AKI was defined as having the first increase in SCr within the early phase (<24 hours), and late CA-AKI was defined as an increase in SCr that occurred for the first time in the late phase (24-72 hours). The first endpoint of this study was long-term all-cause mortality. Kaplan-Meier analysis was used to count the cumulative mortality, and the log-rank test was used to assess differences between curves. Univariate and multivariate cox regression analyses were performed to assess whether patients who developed different type CA-AKI were at increased risk of long-term mortality. RESULTS: The number of deaths in the 3 groups was 407 for normal (12.7%), 106 for early CA-AKI (32.7%) and 57 for late CA-AKI (17.7%), during a median follow-up period of 3.95 years. After adjusting for important clinical variables, early CA-AKI (HR = 1.33, 95% CI: 1.02-1.74, P=0.038) was significantly associated with mortality, while late CA-AKI (HR = 0.92, 95% CI: 0.65-1.31, P=0.633) was not. The same results were found in patients with coronary artery disease, chronic kidney disease, diabetes mellitus, and percutaneous coronary intervention. CONCLUSIONS: Early increases in Scr, i.e., early CA-AKI, have better predictive value for long-term mortality. Therefore, in clinical practice, physicians should pay more attention to patients with early renal injury related to long-term prognosis and give active treatment.

The value of various peritumoral radiomic features in differentiating the invasiveness of adenocarcinoma manifesting as ground-glass nodules.

OBJECTIVES: To evaluate the ability of CT radiomic features extracted from peritumoral parenchyma of 2 mm and 5 mm distinguishing invasive adenocarcinoma (IAC) from adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA). METHODS: For this retrospective study, 121 lung adenocarcinomas appearing as ground-glass nodules on thin-section CT were evaluated. Quantitative radiomic features were extracted from the peritumoral parenchymal region of 2 mm and 5 mm on CT imaging, and the radiomic models of External2 and External5 were constructed. The ROC curves were used to evaluate the performance of different models. Differences between the AUCs were evaluated using DeLong's method. RESULTS: The radiomic scores of IAC were statistically higher than those of MIA/AIS in both the External2 and External5 models. The AUCs of the External2 and External5 models were 0.882, 0.778 in the training cohort and 0.888, 0.804 in the validation cohort, respectively. The AUC of the External2 model was not statistically different from the External5 model both in the training cohort (p = 0.116) and validation cohort (p = 0.423). CONCLUSIONS: The radiomic features extracted from the peritumoral region of 2 mm and 5 mm at thin-section CT showed good predictive values to differentiate the IAC from AIS/MIA. The radiomic features from the peritumoral region of 5 mm provide no additional benefit in distinguishing IAC from MIA/AIS than that of the 2 mm region. KEY POINTS: • The radiomic models from various peritumoral lung parenchyma were developed and validated to predict invasiveness of adenocarcinoma. • The peritumoral parenchyma of lung adenocarcinoma may contain useful information. • Radiomics from peritumoral lung parenchyma of 5 mm provides no added efficiency of the prediction for invasiveness of lung adenocarcinoma.

Sodium houttuyfonate attenuates neurological defects after traumatic brain injury in mice via inhibiting NLRP3 inflammasomes.

Sodium houttuyfonate (SH) is a chemical compound synthesized by houttuynin and sodium bisulfite. As it has antinflammatory effects, SH has been widely used to treat autoimmune diseases, including post events following traumatic brain injury (TBI). Meanwhile, NOD-like receptor with pyrin domain containing-3 (NLRP3) inflammasomes in microglia may play a central role in TBI. But to date, the intracellular mechanisms involved in the anti-inflammatory effects of SH in TBI remain unknown, especially whether regulating NLRP3. To gain an insight into this possibility, we conducted cell culture and biochemical studies on the effect of SH on NLRP3 inflammasome in microglia. The results showed that SH inhibited TLR4 and NLRP3 inflammasome activation in the microglia cell. In parallel, phosphorylation of ERK and NF-κB p65, which play a key role in NLRP3 inflammasome formation, was decreased. Intraperitoneal injection of SH into TBI mice significantly reduced the modified neurological severity score (mNSS), as well as the degree of microglia apoptosis post-controlled cortical impact (CCI). Immunohistochemistry, Western blot analysis, and reverse-transcription polymerase chain reaction (RT-PCR) revealed that SH markedly reduced NLRP3 inflammasome activation, TLR4 activity, phosphorylation of ERK and NF-κB. Moreover, SH significantly inhibited microglia activation post-CCI, but effectively promoted the astrocyte activation and angiopoiesis. Taken together, our research provides evidence that SH attenuated neurological deficits post TBI through inhibiting NLRP3 inflammasome activation, via influencing the TLR4/NF-κB signaling pathway. These findings explain the intracellular mechanism of the anti-inflammatory activity caused by SH treatment following TBI.

Hypertension as a Risk Factor for Contrast-Associated Acute Kidney Injury: A Meta-Analysis Including 2,830,338 Patients.

OBJECTIVE: Previous studies have shown that the relationship between hypertension (HT) and contrast-associated acute kidney injury (CA-AKI) is not clear. We apply a systematic review and meta-analysis to assess the association between HT and CA-AKI. METHODS: We searched for articles on the study of risk factors for CA-AKI in the Embase, Medline, and Cochrane Database of Systematic Reviews (by March 25, 2021). Two authors independently performed quality assessment and extracted data such as the studies' clinical setting, the definition of CA-AKI, and the number of patients. The CA-AKI was defined as a serum creatinine (SCr) increase ≥25% or ≥0.5 mg/dL from baseline within 72 h. We used fixed or random models to pool adjusted OR (aOR) by STATA. RESULTS: A total of 45 studies (2,830,338 patients) were identified, and the average incidence of CA-AKI was 6.48%. There was an increased risk of CA-AKI associated with HT (aOR: 1.378, 95% CI: 1.211-1.567, I2 = 67.9%). In CA-AKI with a SCr increase ≥50% or ≥0.3 mg/dL from baseline within 72 h, an increased risk of CA-AKI was associated with HT (aOR: 1.414, 95% CI: 1.152-1.736, I2 = 0%). In CA-AKI with a Scr increase ≥50% or ≥0.3 mg/dL from baseline within 7 days, HT increases the risk of CA-AKI (aOR: 1.317, 95% CI: 1.049-1.654, I2 = 51.5%). CONCLUSION: Our meta-analysis confirmed that HT is an independent risk factor for CA-AKI and can be used to identify risk stratification. Physicians should pay more attention toward prevention and treatment of patients with HT in clinical practice.

Dual-wavelength excitation combined Raman spectroscopy for detection of highly fluorescent samples.

As fluorescence is the major limitation in Raman scattering, near-infrared excitation wavelength (>780nm) is preferred for fluorescence suppression in Raman spectroscopy. To reduce the risk of fluorescence interference, we developed a dual-wavelength excitation combined Raman spectroscopy (DWECRS) system at 785 and 830 nm. By a common optical path, each laser beam was focused on the same region of the sample by a single objective lens, and the dual-wavelength excitation Raman spectra were detected by a single CCD detector; in addition, 785 and 830 nm excitation Raman spectra can be directly constructed as combined Raman spectrum in the DWECRS system. The results of pure peanut oil and glycerol indicate that the combined Raman spectrum cannot only reduce fluorescence interference but also keep a high signal-to-noise ratio in the high-wavenumber region. The results of dye-ethanol solutions with different concentrations show that the handheld DWECRS system can be used as a smart method to dodge strong fluorescence. Furthermore, we developed a peak intensity ratio method with the DWECRS system to distinguish different types of edible oils. The peak intensity ratio distribution chart of edible oils showed each oil normalized center was relatively independent and nonoverlapped, which can be used as the basis of edible oil classification analysis. In the future, the DWECRS system has potential to be used as a tool for more complex applications.

Dual-wavelength wide area illumination Raman difference spectroscopy for remote detection of chemicals.

Remote Raman instruments have become powerful analytical tools in some special environments. However, ambient daylight is the main limitation in the data acquisition process. To suppress daylight background interference and obtain a high signal-to-background ratio (SBR), we develop a dual-wavelength wide area illumination Raman difference spectroscopy (WAIRDS) system for daytime remote detection. In the WAIRDS system, a wide area illumination scheme and shifted-excitation Raman difference spectroscopy method are used to improve the reliability of collected Raman spectra. Measurements of polystyrene indicate that the WAIRDS system can be operated to obtain background-free Raman spectra under different levels of daylight background interference. The remote results show that the improvement in SBR is about three- to fivefold, and the system can work at distances of up to 9.2 m on a sunny afternoon. Moreover, to be close to the actual detection, the system is used for mineral and explosive raw material detection during daytime measurement. Measurements show that the WAIRDS system will be a useful tool for many remote applications in the future.

Surface-enhanced shifted excitation Raman difference spectroscopy for trace detection of fentanyl in beverages.

In recognition of the misuse risks of fentanyl, there is an urgent need to develop a useful and rapid analytical method to detect and monitor the opioid drug. The surface-enhanced shifted excitation Raman difference spectroscopy (SE-SERDS) method has been demonstrated to suppress background interference and enhance Raman signals. In this study, the SE-SERDS method was used for trace detection of fentanyl in beverages. To prepare the simulated illegal drug-beverages, fentanyls were dissolved into distilled water or Mizone as a series of test samples. Based on our previous work, the surface-enhanced Raman spectroscopy detection was performed on the beverages containing fentanyl by the prepared AgNPs and the SE-SERDS spectra of test samples were collected by the dual-wavelength rapid excitation Raman difference spectroscopy system. In addition, the quantitative relationship between fentanyl concentrations and the Raman peaks was constructed by the Langmuir equation. The experimental results show that the limits of quantitation for fentanyl in distilled water and Mizone were 10 ng/mL and 200 ng/mL, respectively; the correlation coefficients for the nonlinear regression were as high as 0.9802 and 0.9794, respectively; and the relative standard deviation was less than 15%. Hence, the SE-SERDS method will be a promising method for the trace analyses of food safety and forensics.

Effects of different amino acids and their configurations on methane yield and biotransformation of intermediate metabolites during anaerobic digestion.

Anaerobic digestion (AD) comprises a series of biochemical reactions, with methane as one of the target products. Amino acids (AAs) are important molecular and primary intermediate products when protein is the main component of organic waste/wastewater. The L (levorotatory, left-handed)-configuration is natural for AAs, while D (dextrorotatory, right-handed) -AAs also widely exist in the natural environment and can be generated by racemization. However, the effects and underlying mechanisms of natural AAs and their enantiomers on the methane yield and the underlying mechanisms remain unclear. In this study, the effects of certain widespread L-AAs and their enantiomers on two-stage AD and the mechanisms therein were investigated. The AAs enantiomers showed variable or even opposite effects on different processes. The methane yield from a model monosaccharide (glucose) decreased by 57% with D-leucine addition. The butyrate generation and the methane yield from propionate were sensitive to the AA configuration and were inhibited by D-leucine by 80% and 61.8%, respectively, with D-leucine addition, while the volatile fatty acids concentration was slightly increased with the addition of L-leucine. The related mechanisms were further investigated in terms of key enzymes and microbial communities. The addition of D-Leucine decreased acetic acid production from homoacetogens by 30.2% due to the inhibition of key enzymes involved in hydrogen generation and consumption. The transform of butyryl CoA to butyryl phosphate was the rate-limiting step, with the related enzyme (phosphotransbutylase) was inhibited by D-leucine. Furthermore, the bacteria related to butyric acid generation and organic matter degradation were inhibited by D-leucine, while the methanogenic archaea remained stable irrespective of leucine addition. The effect of D-AAs on microorganisms is related to the type of sludge. In this study, the methanogenetic seed sludge was granular and did not dissociate after treatment; however, the D-AAs could trigger biofilm disassembly and reduce the stability of the sludge floc. The study provides a novel method for regulating AD by adding specific AAs with L or D configuration.

Dietary vitamin D interacts with high phosphate-induced cardiac remodeling in rats with normal renal function.

BACKGROUND: Vitamin D (VD) and phosphate (Pi) load are considered as contributors to cardiovascular disease in chronic kidney disease and the general population, but interactive effects of VD and Pi intake on the heart are not clearly illustrated. METHODS: We fed normal male rats with three levels of dietary VD (100, 1100 or 5000 IU/kg chow) and Pi (0.2, 0.6 or 1.6%) (3X3 design) for 8 weeks and examined renal and cardiac function and histology. RESULTS: High dietary Pi decreased plasma and renal Klotho and plasma 25-hydroxyvitamin D, and increased plasma Pi, fibroblast growth factor 23 and parathyroid hormone without affecting renal function, while low Pi increased plasma and renal Klotho. Both low and high VD diets enhanced high Pi-reduced Klotho expression. Low dietary VD reduced-plasma Klotho was rescued by a low Pi diet. High dietary Pi reduced-cardiac ejection fraction was not modified by a low or high VD diet, but the dietary VD effects on cardiac pathologic changes were more complex. High dietary Pi-induced cardiac hypertrophy was attenuated by a low VD and exacerbated by a high VD diet. In contrast, high dietary Pi -induced cardiac fibrosis was magnified by a low VD and attenuated by a high VD diet. CONCLUSIONS: High Pi diet induces hypertrophy and fibrosis in left ventricles, a low VD diet accelerates high Pi-induced fibrosis, and a high VD diet exacerbated high Pi -induced hypertrophy. Therefore, cardiac phosphotoxicity is exacerbated by either high or low dietary VD in rats with normal kidney function.

A comparison between two different definitions of contrast-associated acute kidney injury for long-term mortality in patients with diabetes undergoing coronary angiography: a prospective cohort study.

BACKGROUND: The definitions of contrast-associated acute kidney injury (CA-AKI) are diverse and have different predictive effects for prognosis, which are adverse for clinical practice. Few articles have discussed the relationship between these definitions and long-term prognosis in patients with diabetes. METHODS: A total of 1154 diabetic patients who were undergoing coronary angiography (CAG) were included in this study. Two definitions of CA-AKI were used: CA-AKIA was defined as an increase ≥ 0.3 mg/dl or > 50% in serum creatinine (SCr) from baseline within 72 h after CAG, and CA-AKIB was defined as an increase ≥ 0.5 mg/dl or > 25% in SCr from baseline within 72 h after CAG. We used Cox regression to evaluate the association of these two CA-AKI definitions with long-term mortality and calculate the population attributable risks (PARs) of different definitions for long-term prognosis. RESULTS: During the median follow-up period of 7.4 (6.2-8.2) years, the overall long-term mortality was 18.84%, and the long-term mortality in patients with CA-AKI according to both CA-AKIA and CA-AKIB criteria were 36.73% and 28.86%, respectively. We found that CA-AKIA (HR: 2.349, 95% CI 1.570-3.517, p = 0.001) and CA-AKIB (HR: 1.608, 95% CI 1.106-2.339, p = 0.013) were associated with long-term mortality. The PARs were the highest for CA-AKIA (31.14%), followed by CA-AKIB (14.93%). CONCLUSIONS: CA-AKI is a common complication in diabetic patients receiving CAG. The two CA-AKI definitions are significantly associated with a poor long-term prognosis, and CA-AKIA, with the highest PAR, needs more clinical attention.

Baseline correction method based on improved asymmetrically reweighted penalized least squares for the Raman spectrum.

We present a baseline correction method based on improved asymmetrically reweighted penalized least squares (IarPLS) for the Raman spectrum. This method utilizes a new S-type function to reduce the risk of baseline overestimation and speed up the reweighting process. Simulated spectra with different levels of noise and measured spectra with strong fluorescence background from different samples are used to validate the performance of the proposed algorithm. Considering the drawbacks of the weighting rules for the asymmetrically reweighted penalized least squares (arPLS) method, we adapt an inverse square root unit (ISRU) function, which performs well in baseline correction. Compared with previous penalized least squares methods, such as asymmetric least squares, adaptive iteratively reweighted penalized least squares, and arPLS, experiments with the simulated Raman spectra have confirmed that the proposed method yields better outcomes. Experiments with the measured Raman spectra show that the IarPLS method can improve real Raman spectra within 20 ms. The results show that the proposed method can be successfully applied to the practical Raman spectrum as a strong basis for quantitative analysis.

Characteristics and requirements of hypertensive patients willing to use digital health tools in the Chinese community: a multicentre cross-sectional survey.

BACKGROUND: Digital health tools (WeChat or mobile health apps) provide opportunities for new methods of hypertension management for hypertensive patients. However, the willingness of these patients to use social media and mobile health apps for hypertension management remains unclear. This study explored the characteristics and requirements of patients willing to use digital health (WDH) tools to manage hypertension. METHODS: From February to March 2018, we administered questionnaires to 1089 patients with hypertension at eight Chinese primary medical units. We assessed independent risk factors of WDH and requirement among WDH patients. RESULTS: Overall, 43% (465/1089) of participants were WDH patients, who were younger (58 ± 12 vs 61 ± 13 years) and had a greater proportion of employed individuals (31% vs 14%) and higher education levels (65% vs 52%) than the non-WDH patients (all P < 0.0001). After adjusting for other risk factors, higher education (OR: 0.52; 95% CI: 0.34-0.79), good medicine adherence (OR: 1.5; 95% CI: 1.0-2.3) and blood pressure self-monitoring (OR: 1.6; 95% CI: 1.2-2.3) remained significantly associated with WDH (all P < 0.05). WDH patients responded that digital health tools should try to provide a platform for blood pressure monitoring (42%), medication reminders (41%), hypertension knowledge (39%) and doctor-patient communication (32%). CONCLUSION: Our survey suggested that among hypertensive patients, willingness to use digital health tools was significantly associated with education, medicine adherence and blood pressure self-monitoring. Digital health tool developers and researchers should pay particular attention to recruiting older, less educated and unemployed patients with less willingness and who are less technologically savvy and research the requirements of WDH patients (blood pressure monitoring, medication reminders, and knowledge education) in the future.

Experience in Neurosurgery During the Prevalence of COVID-19.

In order to summarize the experience of neurosurgery in The Third People's Hospital of Hubei Province after the outbreak of COVID-19 in 2019, 28 patients were admitted from January 5, 2020 to February 17, 2020. A series of department formulates and constant improvements were made, including elective operation cancellation, altered conventional outpatient service into online outpatient service, strict control of inter department consultation prevention and entering the department, improvements in operation and treatment processes, and strict ward management. As a result, 1 patient with hypertensive cerebral hemorrhage and deep vein thrombosis of the right lower extremity died suddenly due to pulmonary embolism during anticoagulation treatment. Two patients with deep coma gave up treatment and died. No patient was confirmed to be infected with COVID-19 in hospital. One doctor had a low fever and cough in January, and CT showed a small nodule in the lower left lung. After 2 weeks isolation and oral anti-infective drugs, the chest nodule disappeared. One nurse was isolated as a close contact with infected parents. One nurse was confirmed to be infected with COVID-19 in a mild symptom. She was discharged after being cured in the infected department. In conclusion, measures like sufficient theoretical training and protection upgrading for medical staff, continuous improvement on the understanding of COVID-19 characteristics and transmission routes, formulation of strict department management system, monitoring of patients and their families, could effectively deal with the epidemic situation in the neurosurgery department.

miR-324-5p protects against oxidative stress-induced endothelial progenitor cell injury by targeting Mtfr1.

Endothelial progenitor cells (EPCs) belong to bone marrow-derived myeloid progenitor cells that have strong proliferative ability. Dysregulation of miRNAs after acute myocardial infarction (AMI) can result in EPCs injury, thus we hypothesize that correction of miRNA expression may contribute to the tolerance of EPCs against oxidative stress. The peripheral blood of healthy volunteers and patients with ST-segment elevation myocardial infarction (STEMI) was clinically collected. EPCs derived from peripheral blood were transfected by miR-324-5p mimic and simultaneously handled with hydrogen peroxide (H2 O2 ) to inducing EPCs injury. At 24 hrs after the H2 O2 treatment, cell viability, the uptake capacity on DiI-Ac-LDL, and carrying ability on FITC-UEA-l and multiplication capacity were analyzed. The mechanism process was carefully researched by valued the characteristics of the mitochondrion morphology, membrane potential, ATP levels, and the expressing of apoptosis pathways. Small RNA sequencing indicated that the expression level of miR-324-5p in peripheral blood EPCs of patients with STEMI was significantly lower compared with the healthy volunteers. The Mtfr1 has been confirmed as a targeted gene of miR-324-5p through miRTarBase software and western blot. The miR-324-5p mimic units could be contributed for the improvement of viability, the uptake capacity on DiI-Ac-LDL and carrying ability on FITC-UEA-l and multiplication capacity on oxidative stress-injured EPCs. miR-324-5p could suppress mitochondrial fragmentation, promote membrane potential, and ATP levels, as well as protect against oxidative stress-induced EPCs apoptosis. Our results suggested that miR-324-5p protects against oxidative stress-induced EPCs injury by regulating Mtfr1.

Alpha-Klotho Enrichment in Induced Pluripotent Stem Cell Secretome Contributes to Antioxidative Protection in Acute Lung Injury.

Induced pluripotent stem cells (iPSCs) have been reported to alleviate organ injury, although the mechanisms of action remain unclear and administration of intact cells faces many limitations. We hypothesized that cell-free conditioned media (CM) containing the secretome of iPSCs possess antioxidative constituents that can alleviate pulmonary oxidant stress damage. We derived iPSCs from human dermal fibroblasts and harvested the CM. Addition of iPSC CM to cultured human alveolar type-1 epithelial cells mitigated hyperoxia-induced depletion of endogenous total antioxidant capacity while tracheal instillation of iPSC CM into adult rat lungs enhanced hyperoxia-induced increase in TAC. In both the in vitro and in vivo models, iPSC CM ameliorated oxidative damage to DNA, lipid, and protein, and activated the nuclear factor (erythroid 2)-related factor 2 (Nrf2) network of endogenous antioxidant proteins. Compared with control fibroblast-conditioned or cell-free media, iPSC CM is highly enriched with αKlotho at a concentration up to more than 10-fold of that in normal serum. αKlotho is an essential antioxidative cell maintenance and protective factor and an activator of the Nrf2 network. Immunodepletion of αKlotho reduced iPSC CM-mediated cytoprotection by ∼50%. Thus, the abundant αKlotho content significantly contributes to iPSC-mediated antioxidation and cytoprotection. Results uncover a major mechanism of iPSC action, suggest a fundamental role of αKlotho in iPSC maintenance, and support the translational potential of airway delivery of cell-free iPSC secretome for protection against lung injury. The targeted cell-free secretome-based approach may also be applicable to the amelioration of injury in other organs. Stem Cells 2018;36:616-625.

Oxygen-Deficient Dumbbell-Shaped Anatase TiO2-x Mesocrystals with Nearly 100 % Exposed {101} Facets: Synthesis, Growth Mechanism, and Photocatalytic Performance.

The development of hierarchical TiO2 superstructures with new morphologies and intriguing photoelectric properties for utilizing solar energy is known to be an effective approach to alleviate the serious problems of environmental pollution. Herein, unique oxygen-deficient dumbbell-shaped anatase TiO2-x mesocrystals (DTMCs) enclosed by nearly 100 % {101} facets were readily synthesized by mesoscale transformation in TiCl3 /acetic acid (HAc) mixed solution, followed by calcination under vacuum. These mesocrystals exhibited much higher photoreactivity toward removing the model pollutants methyl orange and CrVI than truncated tetragonal bipyramidal anatase nanocrystals (TNCs), anatase mesocrystals built from truncated tetragonal bipyramidal anatase nanocrystals (TTMCs), and anatase mesocrystals constructed by anatase nanocrystals with nearly 100 % exposed {101} facets (TMCs), revealing that both the oxidation and reduction abilities of anatase TiO2 were simultaneously enhanced upon fabricating an oxygen-deficient mesocrystalline architecture with about 100 % exposed {101} facets. Further characterization illustrated that such an enhancement of photoreactivity was mainly due to the strengthened light absorption, boosted charge carrier separation, and nearly 100 % exposed {101} facets of the oxygen-deficient dumbbell-shaped anatase mesocrystals. This work will be useful for guiding the synthesis of oxygen-deficient ordered superstructures of metal oxides with desired morphologies and exposed facets for promising applications in environmental remediation.

A simple risk score model for predicting contrast-induced nephropathy after coronary angiography in patients with diabetes.

BACKGROUND: Contrast-induced nephropathy (CIN) is a common complication in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) and associated with poor outcome. Some previous studies have already set up models to predict CIN, but there is no model for patients with diabetes mellitus (DM) especially. Therefore, we aim to develop and validate a simple risk score for predicting the risk of CIN in patients with DM undergoing CAG/PCI. METHODS: A total of 1157 consecutive patients with DM undergoing CAG/PCI were randomly assigned to a development cohort (n = 771) and a validation cohort (n = 386). The primary endpoint was CIN, which was defined as an absolute increase in serum creatinine (SCr) by 0.5 mg/dL from the baseline within 48-72 h after contrast exposure. The independent predictors for CIN were identified by multivariate logistic regression, and the discrimination and calibration of the risk score were assessed by ROC curve and Hosmer-Lemeshow test, respectively. RESULTS: The overall incidence of CIN was 45 (3.9%). The new simple risk score (Chen score), which included four independent variables (age > 75 years, acute myocardial infarction, SCr > 1.5 mg/dL, the use of intra-aortic balloon pump), exhibited a similar discrimination and predictive ability on CIN (AUC 0.813, 0.843, 0.796, P > 0.05, respectively), mortality (AUC 0.735, 0.771, 0.826, respectively) and MACEs when being compared with the classical Mehran or ACEF risk score. CONCLUSION: Our data suggest that the new simple risk score might be a good tool for predicting CIN in patients with DM undergoing CAG/PCI.