Phase II study of SOXIRI (S-1/oxaliplatin/irinotecan) chemotherapy in patients with unresectable pancreatic ductal adenocarcinoma.

BACKGROUND: To provide data on the safety and efficacy of a combination chemotherapy regimen consisting of S-1, oxaliplatin, and irinotecan (SOXIRI) as a first-line therapy in unresectable pancreatic ductal adenocarcinoma (UPDA) patients. METHODS: Patients with UPDA and no prior treatment chemotherapy in the UPDA setting were enrolled. The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression-free survival (PFS) and adverse events. Patients received 80 mg/m2 S-1 twice a day for 2 weeks in an alternate-day administration cycle, 85 mg/m2 oxaliplatin on Day 1, and 150 mg/m2 irinotecan on Day 1 of a 2-week cycle. RESULTS: In these 62 enrolled patients, the ORR was 27.4 %, median OS was 12.1 months, and median PFS was 6.5 months. Major grade 3 or 4 toxicity included neutropenia (22.3 %), leucopenia (16.1 %), nausea (9.7 %), vomiting (9.7 %), thrombocytopenia (6.5 %), anorexia (8.5 %), anemia (4.8 %), and diarrhea (1.6 %). No treatment-related deaths occurred. In addition, the analysis of 32 patients suffering pain revealed that the rate of pain relief was 34.4 %. CONCLUSION: SOXIRI might be a standard regimen with an acceptable toxicity profile and favorable efficacy for use as chemotherapy in patients with UPDA.

Outdoor light at night, air pollution and risk of incident type 2 diabetes.

BACKGROUND: Air pollution and outdoor light at night (LAN) have been reported to be related to type 2 diabetes (T2D). However, their interaction with risk of T2D remains uncertain. Therefore, our study aimed to explore the relationship between outdoor LAN, air pollution and incident T2D. METHODS: Our study included a cohort of 24,147 subjects recruited from 2015 to 2018 in Ningbo, China. Land use regression models were used to evaluate particulate matter with a diameter ≤2.5 µm (PM2.5), ≤10 µm (PM10) and nitrogen dioxide (NO2). Satellite images data with a spatial resolution of 500m was used to estimate outdoor LAN levels. T2D new cases were identified by medical records based on health information system. Cox proportional hazards models were used to estimate Hazard ratios (HRs) and 95% confidence intervals (CIs). Moreover, we investigated the multiplicative and additive interactions between air pollution and outdoor LAN. RESULTS: During 108,908 person-years of follow-up period, 1016 T2D incident cases were identified. The HRs (95% CIs) were 1.22 (1.15, 1.30) for outdoor LAN, 1.20 (1.00, 1.45) for PM2.5, 1.23 (1.11, 1.35) for PM10 and 1.19 (1.04, 1.37) for NO2 in every interquartile range increase, respectively. Furthermore, significant interactions were observed between outdoor LAN and NO2. CONCLUSIONS: Our findings indicated that air pollution and outdoor LAN were positively associated with T2D. Moreover, we observed an interaction between outdoor LAN and NO2 suggesting that stronger associations for outdoor LAN and T2D in areas with higher levels of NO2, and for NO2 and T2D in areas with higher levels of outdoor LAN.

Association of fine particulate matter and residential green space with rheumatoid arthritis.

BACKGROUND: Fine particulate matter (PM2.5) is a recognized risk factor for respiratory and cardiovascular diseases, but the association between PM2.5 and rheumatoid arthritis (RA) is still controversial. Additionally, evidence on the relationship of green space with RA is scarce. This study aimed to investigate the separate and combined associations of PM2.5 and green space with risk of RA. METHODS: Our study involved 30,684 participants from the Yinzhou cohort in Ningbo, China. PM2.5 concentrations were determined using a land-use regression model. Residential green space was assessed using the Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) from satellite images. We employed the Cox proportional hazard model to evaluate the relationships of PM2.5 and green space with RA. RESULTS: During the 176,894 person-years of follow-up period, 354 cases of RA were identified. Hazard ratio (HR) and the corresponding 95% confidence interval (95% CI) for every interquartile range (IQR) increase in PM2.5 were 1.23 (95% CI: 1.02, 1.49). Compared with lower exposure to residential green space, individuals living in areas with more green space had a decreased risk of RA (HR was 0.80 (95% CI: 0.70, 0.92), 0.80 (95% CI: 0.70, 0.92), and 0.79 (95% CI: 0.70, 0.89) for 250m, 500m, and 1000m NDVI buffers, respectively). Similar results were observed for the association between EVI and RA. Furthermore, a significant multiplicative interaction was observed between PM2.5 and green space (NDVI 250m and EVI 250m). No mediating effect of PM2.5 on the relationship between green space and RA was observed. CONCLUSION: Our findings indicated that living in areas with higher green space was linked to a reduced risk of RA, whereas living in areas with higher PM2.5 was associated with an increased risk of RA. The beneficial effect of high green space may be offset by exposure to PM2.5.

Enhancement of recombinant human interleukin-22 production by fusing with human serum albumin and supplementing N-acetylcysteine in Pichia Pastoris.

Interleukin-22 (IL-22) plays an important role in the treatment of organ failure, which can induce anti-apoptotic and proliferative signaling pathways; Nevertheless, the practical utilization of IL-22 is hindered by the restricted efficacy of its production. Pichia pastoris presents a viable platform for both industrial and pharmaceutical applications. In this study, we successfully generated a fusion protein consisting of truncated human serum albumin and human IL-22 (HSA-hIL-22) using P. pastoris, and examined the impact of antioxidants on HSA-hIL-22 production. We have achieved the production of HSA-hIL-22 in the culture medium at a yield of approximately 2.25 mg/ml. Moreover, 0-40 mM ascorbic acid supplementation did not significantly affect HSA-hIL-22 production or the growth rate of the recombinant strain. However, 80 mM ascorbic acid treatment had a detrimental effect on the expression of HSA-hIL-22. In addition, 5-10 mM N-acetyl-l-cysteine (NAC) resulted in an increase of HSA-hIL-22 production, accompanied by a reduction in the growth rate of the recombinant strain. Conversely, 20-80 mM NAC supplementation inhibited the growth of the recombinant strains and reduced intact HSA-hIL-22 production. However, neither NAC nor ascorbic acid exhibited any effect on superoxide dismutase (SOD) and malondialdehyde (MDA) levels, except that NAC increased GSH content. Furthermore, our findings indicate that recombinant HSA-hIL-22, which demonstrated the ability to stimulate the proliferation of HepG2 cells, possesses bioactivity. In addition, NAC did not affect HSA-hIL-22 bioactivity. In conclusion, our study demonstrates that NAC supplementation can enhance the secretion of functional HSA-hIL-22 proteins produced in P. pastoris without compromising their activity.

Application of attenuation coefficient in the assessment of hepatic involvement in children and adolescents with Wilson's disease.

BACKGROUND: To investigate whether the attenuation coefficient (ATT) can be used as a noninvasive index to assess liver involvement in children and adolescents with Wilson's disease (WD). METHODS: Children and adolescents diagnosed with WD were retrospectively collected from the First Affiliated Hospital of the Anhui University of Traditional Chinese Medicine between May 2022 and August 2022. The findings on ATT, Shear Wave Measurement (SWM), AST to platelet ratio index (APRI), and fibrosis 4 (FIB-4) score were obtained. The liver involvement of WD was classified into 3 groups based on serum levels of collagen type IV (CIV), hyaluronic acid (HA), laminin (LN) and precollagen type III N-terminal peptide (PIIINP): (1) Group1 (n = 25), no abnormalities in CIV, HA, LN and PIIINP; (2) Group2 (n = 19), elevation of 1 or 2 indexes in CIV, HA, LN, and PIIINP; Group3 (n = 18), elevation of 3 or 4 indicators in CIV, HA, LN, and PIIINP. The levels of ATT, SWM, APRI and FIB-4 were compared between the 3 groups; and correlation of ATT with SWM and triglyceride (TG) was performed using Spearman's correlation analysis. The Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of ATT alone and its combination with SWM, APRI, and FIB-4 in children and adolescents with WD. RESULTS: A total of 62 children and adolescents with WD were retrospectively retrieved. ATT levels were significantly different in intergroup comparisons (P < 0.001). The ROC curve showed that the area under the curve (AUC) for the diagnosis of hepatic steatosis using ATT was 0.714, 0.712 and 0.867 in Group 1 versus Group 2, Group 2 versus Group 3, and Group 1 versus Group 3, respectively; the sensitivity for the diagnosis of hepatic steatosis in Group 1 versus Group 2 was 89.47% with the cutoff value of ATT of 0.73 dB/cm/MHz. No significant correlation found between ATT and TG (ρ = 0.154, P = 0.231). Compared to ATT alone, the combination of ATT with APRI and FIB-4 or the combination of ATT with SWM, APRI, and FIB-4 showed a better diagnostic efficacy in Group 1 versus Group 2 (both P = 0.038). CONCLUSION: ATT could be used as a non-invasive index for the evaluation of liver steatosis in children and adolescents with WD, with a good clinical applicative value. Furthermore, ATT in combination with APRI, FIB-4, and SWM might have better diagnostic efficacy than ATT alone.

An automated detection of epileptic seizures EEG using CNN classifier based on feature fusion with high accuracy.

BACKGROUND: Epilepsy is a neurological disorder that is usually detected by electroencephalogram (EEG) signals. Since manual examination of epilepsy seizures is a laborious and time-consuming process, lots of automatic epilepsy detection algorithms have been proposed. However, most of the available classification algorithms for epilepsy EEG signals adopted a single feature extraction, in turn to result in low classification accuracy. Although a small account of studies have carried out feature fusion, the computational efficiency is reduced due to too many features, because there are also some poor features that interfere with the classification results. METHODS: In order to solve the above problems, an automatic recognition method of epilepsy EEG signals based on feature fusion and selection is proposed in this paper. Firstly, the Approximate Entropy (ApEn), Fuzzy Entropy (FuzzyEn), Sample Entropy (SampEn), and Standard Deviation (STD) mixed features of the subband obtained by the Discrete Wavelet Transform (DWT) decomposition of EEG signals are extracted. Secondly, the random forest algorithm is used for feature selection. Finally, the Convolutional Neural Network (CNN) is used to classify epilepsy EEG signals. RESULTS: The empirical evaluation of the presented algorithm is performed on the benchmark Bonn EEG datasets and New Delhi datasets. In the interictal and ictal classification tasks of Bonn datasets, the proposed model achieves an accuracy of 99.9%, a sensitivity of 100%, a precision of 99.81%, and a specificity of 99.8%. For the interictal-ictal case of New Delhi datasets, the proposed model achieves a classification accuracy of 100%, a sensitivity of 100%, a specificity of 100%, and a precision of 100%. CONCLUSION: The proposed model can effectively realize the high-precision automatic detection and classification of epilepsy EEG signals. This model can provide high-precision automatic detection capability for clinical epilepsy EEG detection. We hope to provide positive implications for the prediction of seizure EEG.

Effect of N-acetyl-l-cysteine on Cell Phenotype and Autophagy in Pichia pastoris Expressing Human Serum Albumin and Porcine Follicle-Stimulating Hormone Fusion Protein.

Pichia pastoris is widely used for the production of recombinant proteins, but the low secretion efficiency hinders its wide application in biopharmaceuticals. Our previous study had shown that N-acetyl-l-cysteine (NAC) promotes human serum albumin and porcine follicle-stimulating hormone fusion protein (HSA-pFSHß) secretion by increasing intracellular GSH levels, but the downstream impact mechanism is not clear. In this study, we investigated the roles of autophagy as well as cell phenotype in NAC promoting HSA-pFSHß secretion. Our results showed that NAC slowed down the cell growth rate, and its effects were unaffected by Congo Red and Calcofluor White. Moreover, NAC affected cell wall composition by increasing chitin content and decreasing ß-1,3-glucan content. In addition, the expressions of vesicular pathway and autophagy-related genes were significantly decreased after NAC treatment. Further studies revealed that autophagy, especially the cytoplasm-to-vacuole targeting (Cvt) pathway, mitophagy and pexophagy, was significantly increased with time, and NAC has a promoting effect on autophagy, especially at 48 h and 72 h of NAC treatment. However, the disruption of mitophagy receptor Atg32, but not pexophagy receptor Atg30, inhibited HSA-pFSHß production, and neither of them inhibited the NAC-promoted effect of HSA-pFSHß. In conclusion, vesicular transport, autophagy and cell wall are all involved in the NAC-promoted HSA-pFSHß secretion and that disruption of the autophagy receptor alone does not inhibit the effect of NAC.

Crystallizing Self-Standing Covalent Organic Framework Membranes for Ultrafast Proton Transport in Flow Batteries.

Covalent organic frameworks (COFs) display great potential to be assembled into proton conductive membranes for their uniform and controllable pore structure, yet constructing self-standing COF membrane with high crystallinity to fully exploit their ordered crystalline channels for efficient ionic conduction remains a great challenge. Here, a macromolecular-mediated crystallization strategy is designed to manipulate the crystallization of self-standing COF membrane, where the -SO3 H groups in introduced sulfonated macromolecule chains function as the sites to interact with the precursors of COF and thus offer long-range ordered template for membrane crystallization. The optimized self-standing COF membrane composed of highly-ordered nanopores exhibits high proton conductivity (75 mS cm-1 at 100 % relative humidity and 20 °C) and excellent flow battery performance, outperforming Nafion 212 and reported membranes. Meanwhile, the long-term run of membrane is achieved with the help of the anchoring effect of flexible macromolecule chains. Our work provides inspiration to design self-standing COF membranes with ordered channels for permselective application.

Acupoint Catgut Embedding as Adjunctive Therapy for Patients With Gallstones.

AIMS OF THIS STUDY: A randomized clinical trial was undertaken to investigate the efficacy of acupoint catgut embedding (ACE) as adjunctive therapy to tauroursodeoxycholic acid (TUDCA) therapy on gallbladder emptying and clinical symptoms in patients with gallstone disease. MATERIALS AND METHODS: Between August 2018 and January 2019, 70 patients with gallstones in our hospital were enrolled in this prospective clinical trial. All the patients were randomly divided into the ACE group (ACE+TUDCA treatment for 8 wk) and the Sham group (Sham ACE+TUDCA treatment for 8 wk). In the ACE group, all the patients were nightly given ACE every 2 weeks, and in 2 groups, every patient took TUDCA 500 mg at bedtime. The parameters about gallbladder emptying were detected by ultrasound before and after the treatment, and the clinical symptom scores were recorded at the same time points. RESULTS: A total of 63 patients with gallstone disease were included in our study, with 33 patients in the ACE group and 30 patients in the Sham group. In the ACE group, the empty volume (EV) and gallbladder ejection fraction (GBEF) were improved after treatment (P<0.05). Almost every symptom score (except symptom 7, P=0.15) and total score were decreased (P<0.05). In the Sham group, the symptom 1, 2, 4, 5 scores, and total score were significantly decreased (P<0.05). Moreover, the residual volume in the ACE group was significantly lower than in the Sham group (P=0.008). The EV and GBEF in the ACE group were higher than that in the Sham group (P<0.05). The score of symptom 6 in the ACE group was lower than that in the Sham group (P=0.008). CONCLUSION: ACE therapy could more effectively improve the gallbladder emptying with a shorter treatment course. Therefore, ACE+TUDCA therapy might be a time-saving treatment for gallstones.

Gravity-driven electrospun membranes for effective removal of perfluoro-organics from synthetic groundwater.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are emerging contaminants in water and soil. Electrospun membranes with open structure could treat PFAS in a gravity-driven mode with ultralow pressure needs. The electrospun ultrathin fibers (67 ± 27 nm) was prepared for the enhanced specific surface area; where polyvinylidene fluoride (PVDF) backbones and the grafted quaternary ammonium moieties (QA; PVDF-g-QA membranes) provided both hydrophobicity and anion-exchange ability (electrostatic interaction). High affinity towards the perfluorooctanoic acid (PFOA)/perfluorooctanesulfonic acid (PFOS) molecules (denoted as PFOX collectively) was observed, and >95% PFOX was removed from synthetic groundwater with a flux of 32.3 Lm-2h-1 at ΔPo = 313 Pa. With a higher octanol/water partitioning coefficient (Log Kow = 6.3) and close dispersion interaction parameter to the membrane backbones (16.6% difference in δd), the effective PFOS removal remained under alkaline and high conductivity conditions due to the intensive hydrophobic interaction compared to that of PFOA. Long-term studies exhibited >90% PFOX removal in an 8 h test with a capacity of 258 L/m2. Under mild regeneration conditions, PFOA and PFOS were concentrated by 35-fold and 39-fold, respectively. Overall, the gravity-driven electrospun PVDF-g-QA membranes, with adsorptive effectiveness and ease of regeneration, showed great potential in PFAS remediation.

Electrostatic-Induced Crystal-Rearrangement of Porous Organic Cage Membrane for CO2 Capture.

Porous Organic Cages (POCs) with tunable tailoring chemistry properties and polymer-like processing conditions are of great potential for molecular selective membranes, but it remains challenging in the assembly of high crystalline POCs with regular nanochannels for effective molecular sieving. Here we report an electrostatic-induced crystal-rearrangement strategy for the design of a POC membrane with heterostructure. Due to electrostatic attraction, ionic liquid molecules induced cage molecules to rearrange into a sub-10 nm uniform and defect-free crystal layer, which displayed competitive CO2 separation performance. The optimized hetero-structured membrane exhibited an attractive CO2 /N2 separation selectivity of over 130, which was superior to the state-of-the-art membranes, accompanied with excellent long-term and thermal shock stability. This strategy provides a new inspiration for the preparation of crystal-rearranged membranes with regular channels for gas molecule sieving.

High-Efficiency CO2 /N2 Separation Enabled by Rotation of Electrostatically Anchored Flexible Ligands in Metal-Organic Framework.

Metal organic frameworks (MOF) are of great potential for molecular separation, but the ligand rotation flexibility makes them remain challenging in the construction of fixed nanochannels for precise sieving. Here we report an electrostatic-anchoring strategy to fix the rotation of 2-methylimidazole (2-MIM) ligand in ZIF-8. Electrostatic inducer trifluoroacetate anchored at and blocked the six-membered windows of ZIF-8, and meanwhile induced the positive 2-MIM rotated from initial 49° to 68°, thus opening neighbored four-membered windows with a constant size of 3.4 Å. The obtained ZIF-8 significantly enhanced the CO2 /N2 adsorption selectivity from 14.02 to 332.86. Further membrane-based separation exhibited an outstanding CO2 /N2 selectivity of up to 137 with a desired permeability of 286 Barrer, which exceeded the 2019 upper bound. This strategy provides a new inspiration for fixing the ligand rotation in soft MOF for desired precise molecular sieving.

Bile Acid Profiles Are Distinct among Patients with Different Etiologies of Chronic Liver Disease.

A significant increase of bile acid (BA) levels has been recognized as a general metabolic phenotype of diverse liver diseases. Monitoring of BA profiles has been proposed for etiology differentiation on liver injury. Here, we quantitatively profiled serum BAs of healthy controls and 719 patients with chronic liver disease of five etiologies, hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic steatohepatitis (NASH), alcohol-induced liver disease (ALD), and primary biliary cirrhosis (PBC), and investigated the generality and specificity of different etiologies. The raw data have been deposited into MetaboLights (ID: MTBLS2459). We found that patients with HBV, HCV, and NASH appeared to be more similar, and ALD and PBC patients clustered together. BA profiles, consisting of a total concentration of the 21 quantified BAs [total BAs (TBAs)], 21 BA proportions, and 24 BA relevant variables, were highly different among the etiologies. Specifically, the total BAs was higher in ALD and PBC patients compared with the other three groups. The proportion of conjugated deoxycholates was the highest in HBV-infected patients. The ratio of 12α-hydroxylated (12α-OH) to non-12α-OH BAs was the highest in NASH patients. The proportion of taurine-conjugated BAs was the highest in ALD patients. For PBC patients, the proportion of ursodeoxycholate species was the highest, and the ratio of primary to secondary BAs was the lowest. Comparatively, the difference of BA profiles among cirrhosis patients was consistent but weaker than that of all patients. The correlations between BA profiles and clinical indices were also quite different in different pathological groups, both in all patients and in patients with cirrhosis. Overall, our findings suggested that BA compositions are distinct among patients with different etiologies of chronic liver disease, and some BA-relevant variables are of clinical potentials for liver injury type differentiation, although further validations on more etiologies and populations are needed.

Epidemiology and Ecology of Severe Fever With Thrombocytopenia Syndrome in China, 2010‒2018.

BACKGROUND: The growing epidemics of severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne disease in East Asia, and its high case fatality rate have raised serious public health concerns. METHODS: Surveillance data on laboratory-confirmed SFTS cases in China were collected. The spatiotemporal dynamics and epidemiological features were explored. The socioeconomic and environmental drivers were identified for SFTS diffusion using survival analysis and for SFTS persistence using a two-stage generalized boosted regression tree model. RESULTS: During 2010‒2018, a total of 7721 laboratory-confirmed SFTS cases were reported in China, with an overall case fatality rate (CFR) of 10.5%. The average annual incidence increased >20 times and endemic areas expanded from 27 to 1574 townships, whereas the CFR declined from 19% to 10% during this period. Four geographical clusters-the Changbai Mountain area, the Jiaodong Peninsula, the Taishan Mountain area, and the Huaiyangshan Mountain area-were identified. Diffusion and persistence of the disease were both driven by elevation, high coverages of woods, crops, and shrubs, and the vicinity of habitats of migratory birds but had different meteorological drivers. Residents ≥60 years old in rural areas with crop fields and tea farms were at increased risk to SFTS. CONCLUSIONS: Surveillance of SFTS and intervention programs need to be targeted at areas ecologically suitability for vector ticks and in the vicinity of migratory birds to curb the growing epidemic.

A Metabolite Array Technology for Precision Medicine.

The application of metabolomics in translational research suffers from several technological bottlenecks, such as data reproducibility issues and the lack of standardization of sample profiling procedures. Here, we report an automated high-throughput metabolite array technology that can rapidly and quantitatively determine 324 metabolites including fatty acids, amino acids, organic acids, carbohydrates, and bile acids. Metabolite identification and quantification is achieved using the Targeted Metabolome Batch Quantification (TMBQ) software, the first cross-vendor data processing pipeline. A test of this metabolite array was performed by analyzing serum samples from patients with chronic liver disease (N = 1234). With high detection efficiency and sensitivity in serum, urine, feces, cell lysates, and liver tissue samples and suitable for different mass spectrometry systems, this metabolite array technology holds great potential for biomarker discovery and high throughput clinical testing. Additionally, data generated from such standardized procedures can be used to generate a clinical metabolomics database suitable for precision medicine in next-generation healthcare.

Ultrafast Water Transport in Two-Dimensional Channels Enabled by Spherical Polyelectrolyte Brushes with Controllable Flexibility.

Fast water transport channels are crucial for water-related membrane separation processes. However, overcoming the trade-off between flux and selectivity is still a major challenge. To address this, we constructed spherical polyelectrolyte brush (SPB) structures with a highly hydrophilic polyelectrolyte brush layer, and introduced them into GO laminates, which increased both the flux and the separation factor. At 70 °C, the flux reached 5.23 kg m-2 h-1 , and the separation factor of butanol/water increased to ≈8000, which places it among the most selective separation membranes reported to date. Interestingly, further studies demonstrated that the enhancement of water transport was not only dependent on the hydrophilicity of the polyelectrolyte chains, but also influenced by their flexibility in the solvent. Quartz crystal microbalance with dissipation and molecular dynamics simulations revealed the structure-performance correlations between water molecule migration and the flexibility of the ordered polymer chains in the 2D confined space.

Serum metabolite profiles are associated with the presence of advanced liver fibrosis in Chinese patients with chronic hepatitis B viral infection.

BACKGROUND: Accurate and noninvasive diagnosis and staging of liver fibrosis are essential for effective clinical management of chronic liver disease (CLD). We aimed to identify serum metabolite markers that reliably predict the stage of fibrosis in CLD patients. METHODS: We quantitatively profiled serum metabolites of participants in 2 independent cohorts. Based on the metabolomics data from cohort 1 (504 HBV associated liver fibrosis patients and 502 normal controls, NC), we selected a panel of 4 predictive metabolite markers. Consequently, we constructed 3 machine learning models with the 4 metabolite markers using random forest (RF), to differentiate CLD patients from normal controls (NC), to differentiate cirrhosis patients from fibrosis patients, and to differentiate advanced fibrosis from early fibrosis, respectively. RESULTS: The panel of 4 metabolite markers consisted of taurocholate, tyrosine, valine, and linoelaidic acid. The RF models of the metabolite panel demonstrated the strongest stratification ability in cohort 1 to diagnose CLD patients from NC (area under the receiver operating characteristic curve (AUROC) = 0.997 and the precision-recall curve (AUPR) = 0.994), to differentiate fibrosis from cirrhosis (0.941, 0.870), and to stage liver fibrosis (0.918, 0.892). The diagnostic accuracy of the models was further validated in an independent cohort 2 consisting of 300 CLD patients with chronic HBV infection and 90 NC. The AUCs of the models were consistently higher than APRI, FIB-4, and AST/ALT ratio, with both greater sensitivity and specificity. CONCLUSIONS: Our study showed that this 4-metabolite panel has potential usefulness in clinical assessments of CLD progression in patients with chronic hepatitis B virus infection.

Fe3O4/PVDF catalytic membrane treatment organic wastewater with simultaneously improved permeability, catalytic property and anti-fouling.

Fe3O4/Polyvinylidene fluoride (PVDF) three-channel hollow fiber catalytic membrane was successfully fabricated via non-solvent induced phase inversion and used for organic wastewater degradation in this work. The effects of Fe3O4 nanoparticles addition on the surface and cross-section morphologies, hydrophilicity and thermal properties of the catalytic membrane were characterized by the field emission scanning electron microscopy (SEM), water contact angle and thermogravimetric analysis (TGA), respectively. The obtained catalytic membrane exhibited good hydrophilicity, a high pure water flux of 175.8 L m-2 h-1 and a high removal of methylene blue (up to 97.6%) with Fenton catalytic reaction. Meanwhile, the catalytic membrane shows excellent anti-fouling property due to the presence of Fenton reaction. Our results show that Fe3O4/PVDF three-channel hollow fiber catalytic membrane was a promising alternative for the degradation of organic contaminants.

Predictors of phthalate metabolites in urine and follicular fluid and correlations between urine and follicular fluid phthalate metabolite concentrations among women undergoing in vitro fertilization.

BACKGROUND: Phthalate metabolites in follicular fluid (FF) may negatively affect normal folliculogenesis; however, the predictors of phthalate metabolite concentrations in urine and FF and relationships between urine and FF phthalate metabolite concentrations among women undergoing in vitro fertilization (IVF) are poorly understood. OBJECTIVE: To investigate predictors of phthalate metabolites in urine and FF and correlations between urine and FF phthalate metabolite concentrations among women undergoing IVF. METHOD: We recruited 305 women seeking infertility treatment at a reproductive center in Wuhan, China, from October to November 2016. Information regarding demographic characteristics, personal care product use and plastic material contact was obtained through direct interviews. Concentrations of 8 phthalate metabolites in urine and FF samples were measured using high-performance liquid chromatography and tandem mass spectrometry. Associations regarding metabolite concentrations in urine and FF samples were analysed by Spearman's correlation and linear regression. Generalized linear regression was used to examine potential predictors of phthalate metabolite concentrations in urine and FF. RESULTS: Weak to moderate associations between urine and FF samples were found for monoethyl phthalate (MEP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) (correlation coefficient: MEP, 0.350; MEOHP, 0.377); no associations were observed for other metabolites. The predictive powers of urinary metabolite concentrations in determining FF metabolite concentrations were uniformly low, with R2 ≤ 0.113. Body mass index (BMI) and educational level were inversely associated with the urinary concentrations of certain metabolites. Higher household income, intake of bottled drinks within 48 h, and use of shower gel and soap were frequently associated with higher urinary metabolite concentrations. BMI, higher household income and use of disposable plastic cups within 48 h were associated with higher metabolite concentrations in FF. CONCLUSION: Phthalate metabolite concentrations in urine and FF vary according to sociodemographic characteristics and lifestyle factors. Phthalate metabolite concentrations in urine may not be appropriate for estimating ovary phthalate exposure.

Analysis of Arabidopsis Accessions Hypersensitive to a Loss of Chloroplast Translation.

Natural accessions of Arabidopsis (Arabidopsis thaliana) differ in their ability to tolerate a loss of chloroplast translation. These differences can be attributed in part to variation in a duplicated nuclear gene (ACC2) that targets homomeric acetyl-coenzyme A carboxylase (ACCase) to plastids. This functional redundancy allows limited fatty acid biosynthesis to occur in the absence of heteromeric ACCase, which is encoded in part by the plastid genome. In the presence of functional ACC2, tolerant alleles of several nuclear genes, not yet identified, enhance the growth of seedlings and embryos disrupted in chloroplast translation. ACC2 knockout mutants, by contrast, are hypersensitive. Here we describe an expanded search for hypersensitive accessions of Arabidopsis, evaluate whether all of these accessions are defective in ACC2, and characterize genotype-to-phenotype relationships for homomeric ACCase variants identified among 855 accessions with sequenced genomes. Null alleles with ACC2 nonsense mutations, frameshift mutations, small deletions, genomic rearrangements, and defects in RNA splicing are included among the most sensitive accessions examined. By contrast, most missense mutations affecting highly conserved residues failed to eliminate ACC2 function. Several accessions were identified where sensitivity could not be attributed to a defect in either ACC2 or Tic20-IV, the chloroplast membrane channel required for ACC2 uptake. Overall, these results underscore the central role of ACC2 in mediating Arabidopsis response to a loss of chloroplast translation, highlight future applications of this system to analyzing chloroplast protein import, and provide valuable insights into the mutational landscape of an important metabolic enzyme that is highly conserved throughout eukaryotes.