Mechanistic Insights into the Role of Polydopamine Interlayer toward Improved Separation Performance of Polyamide Nanofiltration Membranes.

Interlayered thin-film nanocomposite membranes (TFNi) are an emerging type of membranes with great potential to overcome the permeability-selectivity upper bound of conventional thin-film composite (TFC) nanofiltration and reverse osmosis membranes. However, the exact roles of the interlayer and the corresponding mechanisms leading to enhanced separation performance of TFNi membranes remain poorly understood. This study reports a polydopamine (PDA)-intercalated TFNi nanofiltration membrane (PA-PSF2, PDA coating time of 2 h) that possessed nearly an order of magnitude higher water permeance (14.8 ± 0.4 Lm-2 h-1 bar-1) than the control TFC membrane (PA-PFS0, 2.4 ± 0.5 Lm-2 h-1 bar-1). The TFNi membrane further showed enhanced rejection toward a wide range of inorganic salts and small organic molecules (including antibiotics and endocrine disruptors). Detailed mechanistic investigation reveals that the membrane separation performance was enhanced due to both the direct "gutter" effect of the PDA interlayer and its indirect effects resulting from enhanced polyamide formation on the PDA-coated substrate, with the "gutter" effect playing a more dominant role. This study provides a mechanistic and comprehensive framework for the future development of TFNi membranes.

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.

Tannic Acid/Fe3+ Nanoscaffold for Interfacial Polymerization: Toward Enhanced Nanofiltration Performance.

Conventional thin-film composite (TFC) membranes suffer from the trade-off relationship between permeability and selectivity, known as the "upper bound". In this work, we report a high performance thin-film composite membrane prepared on a tannic acid (TA)-Fe nanoscaffold (TFCn) to overcome such upper bound. Specifically, a TA-Fe nanoscaffold was first coated onto a polysulfone substrate, followed by performing an interfacial polymerization reaction between trimesoyl chloride (TMC) and piperazine (PIP). The TA-Fe nanoscaffold enhanced the uptake of amine monomers and provided a platform for their controlled release. The smaller surface pore size of the TA-Fe coated substrate further eliminated the intrusion of polyamide into the substrate pores. The resulting membrane TFCn showed a water permeability of 19.6 ± 0.5 L m2- h-1 bar-1, which was an order of magnitude higher than that of control TFC membrane (2.2 ± 0.3 L m-2 h-1 bar-1). The formation of a more order polyamide rejection layer also significantly enhanced salt rejection (e.g., NaCl, MgCl2, Na2SO4, and MgSO4) and divalent to monovalent ion selectivity (e.g., NaCl/MgSO4). Compared to conventional TFC nanofiltration membranes, the novel TFCn membrane successfully overcame the longstanding permeability and selectivity trade-off. The current work paves a new avenue for fabricating high performance TFC membranes.

Insulin Resistance Predicts Virological Response to Interferon-α in Chronic Hepatitis B Patients.

GOALS: To elucidate impact of insulin resistance (IR) on the response to interferon-α (IFN-α) therapy in chronic hepatitis B (CHB) patients. BACKGROUND: Metabolic factors influencing the virological response of CHB patients on IFN-α treatment are still unexplored. STUDY: Eighty CHB patients were treated with IFN-α for 48 weeks. The IR was evaluated by homeostasis model assessment of IR (HOMA-IR) before treatment. Viral load and biochemical parameters were measured at 12, 24, and 48 weeks after starting treatment, and then 24 weeks after the end of treatment. IFN-γ and tumor necrosis factor-α were tested at baseline and 12 weeks of treatment. RESULTS: Pretreatment HOMA-IR proved to be the only independent predictor of primary nonresponse, as well as the pretreatment HOMA-IR, viral load and primary nonresponse were independently associated with virological response at 24, 48 weeks of treatment and at the follow-up endpoint. The significant higher virological relapse rate in patients with IR was observed in patients with virological response at 48 weeks of treatment. The mean HOMA-IR was significantly lower in virological responders than in virological nonresponders. The secretion of IFN-γ and tumor necrosis factor-α was not induced in patients with IR at 12 weeks after IFN-α treatment. CONCLUSIONS: Our data suggest that IR is strongly associated with virological response, thus reflecting the important role played by metabolic factors in the viral kinetics during IFN-α treatment. These findings suggested clinical application of pretreatment HOMA-IR could enable treatment outcome to be predicted and treatment regimens to be determined.

[Quality assessment and classification of persicae semen based on HPLC-UV fingerprint].

Persicae Semen (PS), a traditional Chinese medicine, has been widely used for the syndrome of blood stasis in China since the Eastern Han Dynasty. In the present study, we developed an HPLC-UV fingerprint analysis method for the quality control of PS. The HPLC fingerprint was performed on Shimadzu Inertsil C18 column (4.6 mm x 250 mm, 5 microm) at 35 degrees C. The mobile phases were composed of acetonitrile and water using a gradient elution. The flow rate was 1.0 mL x min(-1), and the detection wavelength was set at 210 nm. The fingerprint method was validated according to the Guidelines for Traditional Chinese Medicine Injection Fingerprint, and applied to determine 41 batches representative herbs collected from Xinjiang of China. The chromatographic peaks were characterized by UPLC-Q-TOF-MS, and nine of them were identified by comparison with the literature and/or reference standards. In order to classify and assess the samples, hierarchical clustering analysis and partial least square discriminant analysis were performed based on the common chromatographic peaks, and the samples were geographically classified into two classes, with six chemical compounds as classification markers which were significantly different between the two classes (P < 0.05).

Hepatitis B virus infection in clustering of infection in families with unfavorable prognoses in northwest China.

Hepatitis B virus (HBV) infection and its associated liver diseases have characteristics of familial clustering in China. However, the reasons for this are not understood fully. To address this issue, the prevalence HBV infection and the characteristics of unfavorable prognoses in clustering of infection in families in northwest China were investigated. Families with clustering of infection and unfavorable prognoses were enrolled, and general information and serum samples were collected. The clinical features and sequelae of HBV infection were compared among the blood relatives (including the first-, second-, and third-degree blood relatives) and spouses using the chi-square test or Fisher's exact test. A total of 102 clusterings of infection families with unfavorable prognoses were interviewed. In the first-, second-, and third-degree blood relatives and spouses, the prevalences of cirrhosis of the liver were 29.2%, 11.9%, and 8.7%, respectively, while those of hepatocellular carcinoma (HCC) were 21.8%, 1.4%, and 4.3%, respectively (P<0.05). The mean ages of the onset of cirrhosis of the liver in the first-, second-, and third-degree blood relatives and spouses were 57 ± 9.91, 47 ± 9.96, 38 ± 10.35, and 57 ± 8.49 years, respectively, while the mean ages of the onset of HCC were 60 ± 7.92, 49 ± 8.57, 41 ± 3.54, and 50 ± 0 years, respectively, (P<0.05). The first-, second-, and third-degree blood relatives from clustering of infection in families with unfavorable prognoses had prevalences of cirrhosis or HCC in descending order of relationship. The findings suggest that genetic factors may be associated with a familial tendency for cirrhosis of the liver and HCC.

Reduced number of IFN-γ producing cells in peripheral blood is a biomarker for patients with renal cell carcinoma.

Renal cell cancer (RCC) is the most lethal of all the common urologic cancers and constitutes 2.2% of all malignancy diagnoses. The incidence of RCC has been steadily increasing in recent decades. The classic risk factors of RCC include smoking, hypertension, obesity, genetics, and genetic mutations. Recent studies also revealed that RCC was an immunogenic tumor and affected by host immune status. Among the pan-cance, RCC presented with the highest degree of immune infiltration, indicating RCC patients might benefit from immunotherapy. A new immune classification of RCC has been developed by Su et al. based on tumor-infiltrating lymphocytes to guide clinical practice. However, these studies mainly focus on biomarkers derived from tumor microenvironment (TME), the biomarkers based on peripheral blood samples to RCC have rarely been described. We collected peripheral blood samples from RCC patients and their matched healthy controls and detected the number of IL-2 and IFN-γ producing cells by implementing an enzyme-linked immunospot (ELISPOT) assay. This is the first study to report blood-based immune biomarkers for RCC using an ELISPOT assay. Our results suggested the frequency of IFN-γ producing cells but not IL-2 producing cells was associated with RCC risk. These findings warrant further validation in larger prospective studies.

Research on Thermal Decomposition Kinetics and Thermal Safety for a New Epoxiconazole Crystal.

To clarify the thermal safety inherent in a new epoxiconazole crystal, differential scanning calorimetry (DSC) and adiabatic accelerating rate calorimetry (ARC) were used for testing and research. The Friedman method and model method were used to analyze thermal decomposition kinetics based on the DSC data, and the N-order and autocatalytic decomposition reaction kinetic models were established. The double scan method was utilized to verify the autocatalytic effect during the decomposition process. The Friedman method, N-order, and autocatalytic model methods were used to study the substance's thermal decomposition characteristics. ARC data are utilized to verify the aforementioned prediction results and the kinetic parameters that were obtained based on ARC data from N-order and autocatalytic model methods that concur with the simulation results. This paper applies the N-order and autocatalytic model to the kinetic model to further predict thermal safety parameter time to maximum rate under adiabatic conditions.

A novel SARS-CoV-2 related coronavirus with complex recombination isolated from bats in Yunnan province, China.

At the end of 2019, A new type of beta-CoV, SARS-CoV-2 emerged and triggered the COVID-19 pandemic, which spread overwhelmingly around the world in less than a year. However, the origin and direct ancestral viruses of SARS-CoV-2 remain unknown. RaTG13, a novel coronavirus found in bats in China's Yunnan Province, is the closest relative virus of the SARS-CoV-2 identified so far. In this study, a new SARS-CoV-2 related virus, provisionally named PrC31, was discovered in Yunnan province by retrospectively analyse bat next generation sequencing (NGS) data of intestinal samples collected in 2018. PrC31 shared 90.7% and 92.0% nucleotide identities to the genomes of SARS-CoV-2 and the bat SARSr-CoV ZC45, respectively. Sequence alignment of PrC31 showed that several genomic regions, especially orf1a and orf8 had the highest homology with those corresponding genomic regions of SARS-CoV-2 than any other related viruses. Phylogenetic analysis indicated that PrC31 shared a common ancestor with SARS-CoV-2 in evolutionary history. The differences between the PrC31 and SARS-CoV-2 genomes were mainly manifested in the spike genes. The amino acid homology between the receptor binding domains of PrC31 and SARS-CoV-2 was only 64.2%. Importantly, recombination analysis revealed that PrC31 underwent multiple complex recombination events (including three recombination breakpoints) involving the SARS-CoV and SARS-CoV-2 sub-lineages, indicating that PrC31 evolved from yet-to-be-identified intermediate recombination strains. Combined with previous studies, it is revealed that the beta-CoVs may possess a more complex recombination mechanism than we thought.

Thin-Film Composite Membrane Prepared by Interfacial Polymerization on the Integrated ZIF-L Nanosheets Interface for Pervaporation Dehydration.

Thin-film composite (TFC) membranes are attracting wide attention because their ultrathin selective layer usually corresponds to the higher membrane flux for pervaporation. However, the direct preparation of the TFC membranes on ceramic substrates confronted with the great difficulties because the larger pores on ceramic substrate surfaces are detrimental to the formation of an intact polyamide (PA) selective layer produced by interfacial polymerization (IP) reaction. Here, the integrated ZIF-L nanosheets were proposed to be used as an assistance interlayer for the first time to eliminate the existence of the pores of the ceramic support, and provides a better basis for the formation of an intact PA selective layer by IP reaction between TMC and ethylenediamine (EDA). The experimental data obtained in pervaporation (PV) show that the increased flux from 1.1 to 2.9 kg/m2h corresponds to the decreased separation factor from 396 to 110 when the feed concentration of ethanol decreases from 95 wt % to 80 wt % at 50 °C. In addition, the membrane flux increases from 0.8 to 2.5 kg/m2h with a change of the separation factor from 683 to 111 when the operational temperature varies from 30 to 60 °C. These results demonstrate the great potential of the fabricated TFC membranes in practical application for PV dehydration of organic solutions.

Isolation of a Novel Bat Rhabdovirus with Evidence of Human Exposure in China.

Bats are well-recognized reservoirs of zoonotic viruses. Several spillover events from bats to humans have been reported, causing severe epidemic or endemic diseases including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), SARS-CoV, Middle East respiratory syndrome-CoV (MERS-CoV), henipaviruses, and filoviruses. In this study, a novel rhabdovirus species, provisionally named Rhinolophus rhabdovirus DPuer (DPRV), was identified from the horseshoe bat (Rhinolophus affinis) in Yunnan province, China, using next-generation sequencing. DPRV shedding in the spleen, liver, lung, and intestinal contents of wild bats with high viral loads was detected by real-time quantitative PCR, indicating that DPRV has tropism for multiple host tissues. Furthermore, DPRV can replicate in vitro in multiple mammalian cell lines, including BHK-21, A549, and MA104 cells, with the highest efficiency in hamster kidney cell line BHK-21, suggesting infectivity of DPRV in these cell line-derived hosts. Ultrastructure analysis revealed a characteristic bullet-shaped morphology and tightly clustered distribution of DPRV particles in the intracellular space. DPRV replicated efficiently in suckling mouse brains and caused death of suckling mice; death rates increased with passaging of DPRV in suckling mice. Moreover, 421 serum samples were collected from individuals who lived near the bat collection site and had fever symptoms within 1 year. DPRV-specific antibodies were detected in 20 (4.75%) human serum samples by indirect immunofluorescence assay. Furthermore, 10 (2.38%) serum samples were DPRV positive according to plaque reduction neutralization assay, which revealed potential transmission of DPRV from bats to humans and highlighted the potential public health risk. Potential vector association with DPRV was not found with negative viral RNA in bloodsucking arthropods. IMPORTANCE We identified a novel rhabdovirus from the horseshoe bat (Rhinolophus thomasi) in China with probable infectivity in humans. DPRV was isolated in vitro from several mammalian cell lines, indicating wide host tropism, excluding bats, of DPRV. DPRV replicated in the brains of suckling mice, and the death rate of suckling mice increased with passaging of DPRV in vivo. Serological tests indicated the possible infectivity of DPRV in humans and the potential transmission to humans. The present findings provide preliminary evidence for the potential risk of DPRV to public health. Additional studies with active surveillance are needed to address interspecies transmission and determine the pathogenicity of DPRV in humans.

Enhanced UV Emission from ZnO on Silver Nanoparticle Arrays by the Surface Plasmon Resonance Effect.

Periodical silver nanoparticle (NP) arrays were fabricated by magnetron sputtering method with anodic aluminum oxide templates to enhance the UV light emission from ZnO by the surface plasmon resonance effect. Theoretical simulations indicated that the surface plasmon resonance wavelength depended on the diameter and space of Ag NP arrays. By introducing Ag NP arrays with the diameter of 40 nm and space of 100 nm, the photoluminescence intensity of the near band-edge emission from ZnO was twofold enhanced. Time-resolved photoluminescence measurement and energy band analysis indicated that the UV light emission enhancement was attributed to the coupling between the surface plasmons in Ag NP arrays and the excitons in ZnO with the improved spontaneous emission rate and enhanced local electromagnetic fields.

Simulation of crosstalk between small GTPase RhoA and EGFR-ERK signaling pathway via MEKK1.

MOTIVATION: Small GTPase RhoA regulates cell-cycle progression via several mechanisms. Apart from its actions via ROCK, RhoA has recently been found to activate a scaffold protein MEKK1 known to promote ERK activation. We examined whether RhoA can substantially affect ERK activity via this MEKK1-mediated crosstalk between RhoA and EGFR-ERK pathway. By extending the published EGFR-ERK simulation models represented by ordinary differential equations, we developed a simulation model that includes this crosstalk, which was validated with a number of experimental findings and published simulation results. RESULTS: Our simulation suggested that, via this crosstalk, RhoA elevation substantially prolonged duration of ERK activation at both normal and reduced Ras levels. Our model suggests ERK may be activated in the absence of Ras. When Ras is overexpressed, RhoA elevation significantly prolongs duration of ERK activation but reduces the amount of active ERK partly due to competitive binding between ERK and RhoA to MEKK1. Our results indicated possible roles of RhoA in affecting ERK activities via MEKK1-mediated crosstalk, which seems to be supported by indications from several experimental studies that may also implicate the collective regulation of cell fate and progression of cancer and other diseases.

In-silico approaches to multi-target drug discovery : computer aided multi-target drug design, multi-target virtual screening.

Multi-target drugs against selective multiple targets improve therapeutic efficacy, safety and resistance profiles by collective regulations of a primary therapeutic target together with compensatory elements and resistance activities. Efforts have been made to employ in-silico methods for facilitating the search and design of selective multi-target agents. These methods have shown promising potential in facilitating drug discovery directed at selective multiple targets.

Consensus model for identification of novel PI3K inhibitors in large chemical library.

Phosphoinositide 3-kinases (PI3Ks) inhibitors have treatment potential for cancer, diabetes, cardiovascular disease, chronic inflammation and asthma. A consensus model consisting of three base classifiers (AODE, kNN, and SVM) trained with 1,283 positive compounds (PI3K inhibitors), 16 negative compounds (PI3K non-inhibitors) and 64,078 generated putative negatives was developed for predicting compounds with PI3K inhibitory activity of IC(50) < or = 10 microM. The consensus model has an estimated false positive rate of 0.75%. Nine novel potential inhibitors were identified using the consensus model and several of these contain structural features that are consistent with those found to be important for PI3K inhibitory activities. An advantage of the current model is that it does not require knowledge of 3D structural information of the various PI3K isoforms, which is not readily available for all isoforms.

Seven-senescence-associated gene signature predicts overall survival for Asian patients with hepatocellular carcinoma.

BACKGROUND: Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma (HCC). The expression of a cluster of genes is altered in response to environmental factors during senescence. However, it is questionable whether these genes could serve as biomarkers for HCC patients. AIM: To develop a signature of senescence-associated genes (SAGs) that predicts patients' overall survival (OS) to improve prognosis prediction of HCC. METHODS: SAGs were identified using two senescent cell models. Univariate COX regression analysis was performed to screen the candidate genes significantly associated with OS of HCC in a discovery cohort (GSE14520) for the least absolute shrinkage and selection operator modelling. Prognostic value of this seven-gene signature was evaluated using two independent cohorts retrieved from the GEO (GSE14520) and the Cancer Genome Atlas datasets, respectively. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive accuracy of the seven-SAG signature and serum α-fetoprotein (AFP). RESULTS: A total of 42 SAGs were screened and seven of them, including KIF18B, CEP55, CIT, MCM7, CDC45, EZH2, and MCM5, were used to construct a prognostic formula. All seven genes were significantly downregulated in senescent cells and upregulated in HCC tissues. Survival analysis indicated that our seven-SAG signature was strongly associated with OS, especially in Asian populations, both in discovery and validation cohorts. Moreover, time-dependent ROC curve analysis suggested the seven-gene signature had a better predictive accuracy than serum AFP in predicting HCC patients' 1-, 3-, and 5-year OS. CONCLUSION: We developed a seven-SAG signature, which could predict OS of Asian HCC patients. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.

Double-Crosslinked GO Interlayer Framework as a Pervaporation Hybrid Membrane with High Performance.

Graphene oxide (GO), as a two-dimensional structure material, has attracted widespread attention in the field of molecule sieving. However, GO-based membranes usually exhibit undesirable separation performance because the microstructure of GO is difficult to adjust. Herein, a novel double-crosslinking strategy for tuning the interlayer spacing of GO is reported. The hybrid membrane fabricated by the double-crosslinking strategy was used for pervaporation (PV) dehydration of isopropanol. To achieve high-performance of the PV hybrid membranes, the effects of operating cycles, chitosan concentration, and GO concentration were systematically investigated. The PV hybrid membranes were characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, water contact angle measurement, and scanning electron microscopy. The results demonstrate that the interlayer of GO can be adjusted successfully by the double-crosslinking strategy. The fabricated hybrid membrane containing 0.1 wt % GO exhibited excellent performance with a flux of 4391 g/m2h and a separation factor of 1491, which indicated that the double-crosslinking strategy may extend the applications of GO in the field of membrane separation.

Simulation of the regulation of EGFR endocytosis and EGFR-ERK signaling by endophilin-mediated RhoA-EGFR crosstalk.

Deregulations of EGFR endocytosis in EGFR-ERK signaling are known to cause cancers and developmental disorders. Mutations that impaired c-Cbl-EGFR association delay EGFR endocytosis and produce higher mitogenic signals in lung cancer. ROCK, an effector of small GTPase RhoA was shown to negatively regulate EGFR endocytosis via endophilin A1. A mathematical model was developed to study how RhoA and ROCK regulate EGFR endocytosis. Our study suggested that over-expressing RhoA as well as ROCK prolonged ERK activation partly by reducing EGFR endocytosis. Overall, our study hypothesized an alternative role of RhoA in tumorigenesis in addition to its regulation of cytoskeleton and cell motility.

Support vector machines approach for predicting druggable proteins: recent progress in its exploration and investigation of its usefulness.

Identification and validation of viable targets is an important first step in drug discovery and new methods, and integrated approaches are continuously explored to improve the discovery rate and exploration of new drug targets. An in silico machine learning method, support vector machines, has been explored as a new method for predicting druggable proteins from amino acid sequence independent of sequence similarity, thereby facilitating the prediction of druggable proteins that exhibit no or low homology to known targets.

[Study of binocular function in early stage after implantation of multifocal intraocular lens].

OBJECTIVE: To evaluate binocular function in the early stage after implantation of multifocal intraocular lens. METHODS: Three weeks postoperatively, simultaneous perception, fusion, near and far-distance stereoacuity, visual acuity and visual symptoms were observed in 31 cases (46 eyes) with multifocal intraocular lens implantation (MIOL) [MIOL group, in which 16 cases with unilateral implantation (Ms) and 15 cases with bilateral implantation (Md)] and 32 cases (47 eyes) with single-focal intraocular lens implantation (SIOL) [SIOL group, in which 17 cases with unilateral implantation (Ss) and 15 cases with bilateral implantation (Sd)]. RESULTS: All patients obtained simultaneous perception and fusion sense, there was no significantly statistical difference between these two group (P > 0.05). Foveal far-distance stereoacuity was established in 38.7% cases among MIOL group (12/31) and 40.6% in SIOL group (13/32), with no statistically significant difference between these two groups (P > 0.05). Foveal near-distance stereoacuity was established in 41.9% MIOL cases (13/31) and in 15.6% SIOL group (5/32), the difference was statistically significant (P < 0.05). Foveal near and far-distance stereoacuity of either Ms and Md or Ss and Sd revealed no significantly statistical difference (P > 0.05). Two patients (6.5%) with MIOL in only one eye complained glare at night, others were satisfied. The stereopsis visual performance such as the quality of vision during eating, up-and-down stairs was improved in MIOL group [80.6% (25/31)] and in SIOL group [56.2% (18/32)], the difference was statistically significant (P < 0.05). CONCLUSIONS: There is a complete recovery of binocular vision in the early post-operative stage of MIOL implantation as compared with the normal value of aged people. Foveal near and far-distance stereoacuity after bilateral and unilateral implantation of either MIOL or SIOL revealed no statistically significant difference. Foveal near-distance stereopsis acuity of MIOL group was improved more quickly than that of SIOL group. MIOL has distinct advantage in providing whole-distance visual acuity and stereoacuity.