PTPN9 dephosphorylates FGFR2 pY656/657 through interaction with ACAP1 and ameliorates pemigatinib effect in cholangiocarcinoma.

ABSTRACT AND AIM: Cholangiocarcinoma (CCA) is a highly aggressive and lethal cancer that originates from the biliary epithelium. Systemic treatment options for CCA are currently limited, and the first targeted drug of CCA, pemigatinib, emerged in 2020 for CCA treatment by inhibiting FGFR2 phosphorylation. However, the regulatory mechanism of FGFR2 phosphorylation is not fully elucidated. APPROACH AND RESULTS: Here we screened the FGFR2-interacting proteins and showed that protein tyrosine phosphatase (PTP) N9 interacts with FGFR2 and negatively regulates FGFR2 pY656/657 . Using phosphatase activity assays and modeling the FGFR2-PTPN9 complex structure, we identified FGFR2 pY656/657 as a substrate of PTPN9, and found that sec. 14p domain of PTPN9 interacts with FGFR2 through ACAP1 mediation. Coexpression of PTPN9 and ACAP1 indicates a favorable prognosis for CCA. In addition, we identified key amino acids and motifs involved in the sec. 14p-APCP1-FGFR2 interaction, including the "YRETRRKE" motif of sec. 14p, Y471 of PTPN9, as well as the PH and Arf-GAP domain of ACAP1. Moreover, we discovered that the FGFR2 I654V substitution can decrease PTPN9-FGFR2 interaction and thereby reduce the effectiveness of pemigatinib treatment. Using a series of in vitro and in vivo experiments including patient-derived xenografts (PDX), we showed that PTPN9 synergistically enhances pemigatinib effectiveness and suppresses CCA proliferation, migration, and invasion by inhibiting FGFR2 pY656/657 . CONCLUSIONS: Our study identifies PTPN9 as a negative regulator of FGFR2 phosphorylation and a synergistic factor for pemigatinib treatment. The molecular mechanism, oncogenic function, and clinical significance of the PTPN9-ACAP1-FGFR2 complex are revealed, providing more evidence for CCA precision treatment.

Panda-UV Unlocks Deeper Protein Characterization with Internal Fragments in Ultraviolet Photodissociation Mass Spectrometry.

Ultraviolet photodissociation (UVPD) mass spectrometry unlocks insights into the protein structure and sequence through fragmentation patterns. While N- and C-terminal fragments are traditionally relied upon, this work highlights the critical role of internal fragments in achieving near-complete sequencing of protein. Previous limitations of internal fragment utilization, owing to their abundance and potential for random matching, are addressed here with the development of Panda-UV, a novel software tool combining spectral calibration, and Pearson correlation coefficient scoring for confident fragment assignment. Panda-UV showcases its power through comprehensive benchmarks on three model proteins. The inclusion of internal fragments boosts identified fragment numbers by 26% and enhances average protein sequence coverage to a remarkable 93% for intact proteins, unlocking the hidden region of the largest protein carbonic anhydrase II in model proteins. Notably, an average of 65% of internal fragments can be identified in multiple replicates, demonstrating the high confidence of the fragments Panda-UV provided. Finally, the sequence coverages of mAb subunits can be increased up to 86% and the complementary determining regions (CDRs) are nearly completely sequenced in a single experiment. The source codes of Panda-UV are available at https://github.com/PHOENIXcenter/Panda-UV.

BRF2 is mediated by microRNA-409-3p and promotes invasion and metastasis of HCC through the Wnt/ß-catenin pathway.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Its invasiveness and ability to metastasize contributes to an extremely high patient mortality. However, the molecular mechanisms that underlie the characteristics of HCC progression are not well understood. BRF2 has been shown to be an oncogene in a number of tumors; however, its role in HCC has not yet been thoroughly examined. In this study, we identified and validated BRF2 as an oncogene in HCC, providing a new insight into HCC pathogenesis and therapeutic possibilities. We showed that BRF2 expression was significantly upregulated in HCC cell lines and tissues, while BRF2 depletion suppressed HCC metastasis and invasion. We then examined the upstream regulation of BRF2 and identified miR-409-3p as being predicted to bind to the 3' UTR of BRF2. We used a luciferase activity assay and functional verification to show that BRF2 is downregulated by miR-409-3p. Finally, we used bioinformatic analysis to show that BRF2 may be related to early HCC development through the Wnt/ß-catenin signaling pathway.

Inhibition of YAP Sensitizes the Selumetinib Treatment for Neurofibromatosis Type 1 Related Plexiform Neurofibroma.

Background: Targeted therapy of Neurofibromatosis type 1 (NF1) related plexiform neurofibroma (pNF) aiming at MEK molecule has not demonstrated a convincing result for complete disease inhibition, probably due to other signal pathways crosstalk. Our previous study revealed an increased nuclear translocation of YAP molecule in NF1 related pNF. Herein, we decided to further investigate the therapeutic relations of YAP interference during the MEK treatment against NF1 related pNF. Methods: By means of selumetinib (MEK-inhibitor), RNA-sequencing was firstly performed to identify the changes of signal pathways in pNF Schwann cells, which was probably related to YAP regulation. Nuclear-cytoplasmic fractionation and western blotting were performed to show the intracellular YAP changes under selumetinib treatment. Thirdly, a series of in vitro assays were performed including flow cytometry, CCK-8, and colony/sphere formation under dual treatment of selumetinib and verteporfin (YAP-inhibitor). In addition, Chou-Talalay method was adopted to evaluate the synergistic inhibiting effects of such drug combination. Xenograft study was also used to detect the combining effects in vivo. Results: RNA-sequencing revealed that selumetinib treatment might be associated with the undesirable activation of Hippo pathway in NF1 related pNF tumor cells, which might reduce its pharmaceutic effects. Next, nuclear-cytoplasmic fractionation and further studies demonstrated that selumetinib could promote the nuclear translocation and transcriptional activation of YAP in vitro, which might cause the aforementioned resistance to selumetinib treatment. Additionally, when combined treatments were performed based on verteporfin and selumetinib, synergistic effects were observed on cytotoxicity of NF1 related pNF tumor cells in vitro and in vivo xenograft models. Conclusion: YAP inhibition can effectively sensitize NF1 related pNF tumor cells to selumetinib. Dual targeting of YAP and MEK might be a promising therapeutic strategy for treating NF1 related pNF.

BMI1 promotes cholangiocarcinoma progression and correlates with antitumor immunity in an exosome-dependent manner.

BACKGROUND: Cholangiocarcinoma (CCA) is a class of malignant tumors originating from bile duct epithelial cells. Due to difficult early diagnosis and limited treatment, the prognosis of CCA is extremely poor. BMI1 is dysregulated in many human malignancies. However, the prognostic significance and oncogenic role of BMI1 in cholangiocarcinoma (CCA) are not well elucidated. METHODS: In the present study, we investigated its clinical importance and the potential mechanisms in the progression of CCA. We detected BMI1 expression in a large CCA cohort. We demonstrated that BMI1 was substantially upregulated in CCA tissues and was identified as an independent prognostic biomarker of CCA. Moreover, overexpression of BMI1 promoted CCA proliferation, migration, and invasion. And BMI1 knockdown could inhibit proliferation and metastases of CCA in vitro and in vitro/vivo validation. Interestingly, we found that CCA-derived exosomes contain BMI1 proteins, which can transfer BMI1 between CCA cells. The unique BMI1-containing exosomes promote CCA proliferation and metastasis through autocrine/paracrine mechanisms. In addition, we demonstrated that BMI1 inhibits CD8+T cell-recruiting chemokines by promoting repressive H2A ubiquitination in CCA cells. CONCLUSIONS: BMI1 is an unfavorable prognostic biomarker of CCA. Our data depict a novel function of BMI1 in CCA tumorigenesis and metastasis mediated by exosomes. Besides, BMI1 inhibition may augment immune checkpoint blockade to inhibit tumor progression by activating cell-intrinsic immunity of CCA.

Excessive fluoride impairs autophagy flux in ameloblasts which is prevented by the autophagy activator rapamycin.

Excessive fluoride intake can cause dental fluorosis during teeth development and growth. However, the mechanisms underlying fluoride-induced enamel damage are still not fully elucidated. Previously, we observed fluoride-induced autophagy in ameloblasts, but the effects of fluoride on autophagy flux in ameloblasts remain unclear. Hence, this study aimed to clarify the effects of fluoride and rapamycin, an autophagy activator, on autophagy flux in ameloblasts. This in vitro study used the murine ameloblast-derived cell line LS8. Cells were treated with different concentrations of sodium fluoride (NaF) to evaluate NaF-induced cytotoxicity. Using transmission electron microscopy, we observed an increase in the number of autophagosomes with increasing fluoride concentrations. Western blot analyses showed increases in microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1 (p62) expression after NaF treatment and an increase in LC3II expression after bafilomycin A1 administration. Together with changes in RFP-GFP-LC3 lentivirus expression, this demonstrated that fluoride impaired autophagy flux. Furthermore, we evaluated whether rapamycin can alleviate fluoride-induced cytotoxicity by restoring autophagy flux. Compared to the NaF-treated group, LS8 cells cotreated with NaF and rapamycin grew considerably better and had significantly decreased p62 expression. Taken together, these data suggest that fluoride-induced impaired autophagosome degradation may damage ameloblasts. This provides experimental in vitro evidence and an explanation for the observed NaF-induced toxicity of ameloblasts. Rapamycin probably alleviates this impairment by decreasing the expression of p62, thereby preventing autophagy defects.

Enantioselective Dearomative [3 + 2] Umpolung Annulation of N-Heteroarenes with Alkynes.

Enantioselective [3 + 2] annulation of N-heteroarenes with alkynes has been developed via a cobalt-catalyzed dearomative umpolung strategy in the presence of chiral ligand and reducing reagent. A variety of electron-deficient N-heteroarenes, including quinolines, isoquinolines, quinoxaline, and pyridines, and internal or terminal alkynes are employed in this reaction, showing a broad substrate scope and good functionality tolerance. Annulation of electron-rich indoles with alkynes is also developed. This protocol provides a straightforward access to a variety of N-spiroheterocyclic molecules in excellent enantioselectivities (76 examples, up to 99% ee).

Impact of bowel preparation on elective colectomies for diverticulitis: analysis of the NSQIP database.

BACKGROUND: Recent data based on large databases show that bowel preparation (BP) is associated with improved outcomes in patients undergoing elective colorectal surgery. However, it remains unclear whether BP in elective colectomies would lead to similar results in patients with diverticulitis. The purpose of this study was to investigate whether bowel preparation affected the surgical site infections (SSI) and anastomotic leakage (AL) in patients with diverticulitis undergoing elective colectomies. STUDY DESIGN: We identified 16,380 diverticulitis patients who underwent elective colectomies from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) colectomy targeted database (2012-2017). Multivariate logistic regression models were employed to investigate the impact of different bowel preparation strategies on postoperative complications, including SSI and AL. RESULTS: In the identified population, a total of 2524 patients (15.4%) received no preparation (NP), 4715 (28.8%) mechanical bowel preparation (MBP) alone, 739 (4.5%) antibiotic bowel preparation (ABP) alone, and 8402 (51.3%) MBP + ABP. Compared to NP, patients who received any type of bowel preparations showed a significantly decreased risk of SSI and AL after adjustment for potential confounders (SSI: MBP [OR = 0.82, 95%CI: 0.70-0.96], ABP [0.69, 95%CI: 0.52-0.92]; AL: MBP [OR = 0.66, 95%CI: 0.51-0.86], ABP [0.56, 95%CI: 0.34-0.93]), where the combination type of MBP + ABP had the strongest effect (SSI:OR = 0.58, 95%CI:0.50-0.67; AL:OR = 0.46, 95%CI:0.36-0.59). The significantly decreased risk of 30-day mortality was observed in the bowel preparation of MBP + ABP only (OR = 0.32, 95%CI: 0.13-0.79). After the further stratification by surgery procedures, patients who received MBP + ABP showed consistently lower risk for both SSI and AL when undergoing open and laparoscopic surgeries (Open: SSI [OR = 0.51, 95%CI: 0.37-0.69], AL [OR = 0.47, 95%CI: 0.25-0.91]; Laparoscopic: SSI [OR = 0.58, 95%CI: 0.47-0.72, AL [OR = 0.49, 95%CI: 0.35-0.68]). CONCLUSIONS: MBP + ABP for diverticulitis patients undergoing elective open or laparoscopic colectomies was associated with decreased risk of SSI, AL, and 30-day mortality. Benefits of MBP + ABP for diverticulitis patients underwent robotic surgeries warrant further investigation.

WDR5 facilitates EMT and metastasis of CCA by increasing HIF-1α accumulation in Myc-dependent and independent pathways.

Cholangiocarcinoma (CCA) is a highly aggressive malignancy with extremely poor prognoses. The oncogenic role and prognostic value of c-Myc in CCA is not well elucidated. WD repeat domain 5 (WDR5) is a critical regulatory factor directly interacting with c-Myc to regulate c-Myc recruitment at chromosomal locations, but the interaction of WDR5 and c-Myc in CCA was uncovered. In our study, we detected WDR5 and c-Myc expression in all CCA types, including intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) CCA, and evaluated their prognostic significance. Consequently, we demonstrated that WDR5 was significantly correlated with poor prognosis of CCA and that WDR5 and c-Myc co-expression was a more sensitive prognostic factor. With in vitro and in vivo experiments and bioinformatics, we showed that WDR5 interacted with the Myc box IIIb (MBIIIb) motif of c-Myc and facilitated Myc-induced HIF1A transcription, thereby promoting the epithelial-mesenchymal transition (EMT), invasion, and metastasis of CCA. Moreover, WDR5 enhanced hypoxia-inducible factor 1 subunit α (HIF-1α) accumulation by binding with histone deacetylase 2 (HDAC2) and increasing histone 3 lysine 4 acetylation (H3K4ac) deacetylation of the prolyl hydroxylase domain protein 2 (PHD2) promoter, resulting in the attenuation of chromatin opening and PHD2 expression, and eventually leading to HIF-1α stabilization and accumulation. In conclusion, WDR5 facilitated EMT and metastasis of CCA by increasing HIF-1α accumulation in a Myc-dependent pathway to promote HIF-1α transcription and a Myc-independent pathway to stabilize HIF-1α.

Passivation of black phosphorus nanoflakes embedded in a silica glass matrix affords ambient saturable absorption stability enhancement.

Black phosphorus (BP) is a graphene analogue with ultrafast broadband nonlinear optical properties that make it a promising nanomaterial for saturable absorption. However, BP nanoflakes chemically degrade in ambient conditions. We developed air- and photo-stable BP nanoflakes via incorporation in inorganic-organic hybrid matrices. This realized passivation and materialization through a sol-gel method that produced high-quality, transparent bulk materials. Saturable absorption parameters of the passivated BP were maintained after five months in ambient storage and after 8000 300 µJ nanosecond laser shots. The nonlinear absorption coefficient was still 62% after 12 months in open air, which was higher than that for non-passivated BP after three days. The stability was attributed to dense silica-gel glasses that enveloped the BP, essentially eliminating oxygen and water penetration. The simplicity of this approach may stimulate potential applications for environmentally sensitive high-performance solid-state devices.

Augmented Corticotomy on the Lingual Side in Mandibular Anterior Region Assisting Orthodontics in Protrusive Malocclusion: A Case Report.

Adequate alveolar bone volume is a prerequisite condition for successful orthodontic tooth movement and posttreatment stability. Mandibular anterior teeth are more likely to exhibit dehiscence and fenestration in adult patients, which make orthodontic treatment in adults challenging, especially when the amount of retraction of the anterior teeth is large. Herein, we report the treatment of augmented corticotomy only on the lingual side in the mandibular anterior region to increase the volume of soft and hard tissue assisting orthodontics in a Class I bialveolar protrusive malocclusion and propose management strategies of mandibular incisor retractions. A 22-year-old female with a chief complaint of protrusive mouth presented to the Department of Orthodontics for orthodontic treatment, diagnosed with Class I bialveolar protrusive. The orthodontic treatment plan involved the extraction of four premolars and extensive retraction of the anterior teeth using microimplant anchorage. In consideration of the fenestration and dehiscence in the mandibular anterior alveolar bone and the pattern of tooth movement, augmented corticotomy was performed on the lingual side combined with bone grafting. Clinical and radiographic evaluation after treatment revealed significant improvements in the facial profile and in periodontal phenotype. Augmented corticotomy assisting orthodontic treatment could be a promising treatment strategy for adult patients with alveolar protrusion to maintain periodontal health.

Epidemiological and clinical characteristics of imported cases of COVID-19: a multicenter study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to expand. Herein, we report the epidemiological and clinical features of 478 patients with confirmed COVID-19 from a multicenter study conducted in four cities in China excluding Wuhan. METHODS: A total of 478 patients transferred by emergency medical services to designated hospitals in four major cities in China (Beijing, Chongqing, Jinan, and Nanning) were enrolled. We compared the characteristics of imported and indigenous cases and calculated the frequencies of fatal, severe, mild, and asymptomatic disease. The results were used to generate a pyramid of COVID-19 severity. RESULTS: The mean age of patients with COVID-19 was 46.9 years and 49.8% were male. The most common symptoms at onset were fever (69.7%), cough (47.5%), fatigue (24.5%), dyspnea (8.4%), and headache (7.9%). Most cases (313, 65.5%) were indigenous, while 165 (34.5%) were imported. Imported cases dominated during the early stages of the pandemic, but decreased from 1 February 2020 as indigenous cases rose sharply. Compared with indigenous cases, imported cases differed significantly in terms of sex (P = 0.002), severity of disease (P = 0.006), occurrence of fever (P < 0.001), family clustering (P < 0.001), history of contact (P < 0.001), and primary outcome (P < 0.001). CONCLUSIONS: Within the population studied, imported cases had distinct characteristics from those of indigenous cases, with lower fatality rates and higher discharge rates. New infections shifted from imported cases to local infection gradually, and overall infections have declined to a low level. We suggest that preventing import of cases and controlling spread within local areas can help prevent SARS-CoV-2 infection spread.

MiR-375 Impairs the Invasive Capabilities of Hepatoma Cells by Targeting HIF1α Under Hypoxia.

BACKGROUND AND AIMS: Hypoxia represents one of the most pervasive microenvironmental stresses in HCC due to the overwhelming growth and inadequate blood supply. HIF1α as an important transcription factor participates in the regulation of various biological behaviors of HCC cells under hypoxia. Our previous study indicated that miR-375 is a hypoxia-associated miRNA. However, the interaction between miR-375 and HIF1α remains unclear. METHODS: Bioinformatic analysis was performed for miRNA screening. qRT-PCR, western blotting, and immunohistochemical staining were used to detect the expression of related molecules. Bioinformatic analysis and dual luciferase assay were used to predict and further confirm the target association. Transwell chamber assay and flow cytometry were, respectively, used to detect migration, invasion and apoptosis of hepatoma cells. RESULTS: MiR-375 presented an obviously differential expression in human HCCs versus background livers (BLs) and HCCs versus normal liver tissues (NLTs). In rat models, miR-375 was gradually declined during hepatocarcinogenesis. HIF1α was remarkably upregulated at protein level rather than at mRNA level in human HCCs versus BLs, HCCs versus NLTs, BLs versus NLTs, and in rat fibrotic livers versus NLTs. HIF1α was determined to be a target of miR-375. MiR-375 inhibitor induced the migration and invasive capabilities and attenuated apoptosis of hepatoma cells under hypoxia. Depriving HIF1α by siRNA could partially reverse the function of miR-375 inhibitor under hypoxia. CONCLUSIONS: MiR-375 impairs the invasive capabilities of HCC cells by targeting HIF1α under hypoxia.

Increased nuclear translation of YAP might act as a potential therapeutic target for NF1-related plexiform neurofibroma.

Plexiform neurofibroma (pNF) in the head and neck is a characteristic feature in patients with neurofibromatosis type 1 (NF1) and is associated with significant disfigurement and psychological distress. Yes-associated protein (YAP), the key molecule involved in the Hippo pathway, is a vital transductor that regulates the proliferation and remyelinating of Schwann cells. The functional status of YAP and its feasibility as a potential target are still unknown in pNF. A total of 17 pNF tumor tissue specimens from the head and neck were collected at the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Histologically, diagnosis of the Schwann cell region in pNF was achieved with hematoxylin-eosin staining, positive reactions for S100, SOX10, ERK and p-ERK, and low identification of Ki67 and SMA. Compared with normal nerve tissue, obviously increased nuclear YAP was detected in the Schwann cell region of pNF, with a mean nuclear staining rate of 67.11%. Based on the shNF1 Schwann cell model (the RSC96 cell line), with upregulated expression of RAS, ERK and p-ERK, p-YAP (Ser127) and p-YAP (Ser397) were significantly decreased and total YAP and nuclear YAP were increased. According to a confocal assay, the interference of shNF1 substantially promoted YAP nuclear translocation. Compared with control Schwann cells, the YAP inhibitor CA3 might have a more sensitive effect (IC50: NC=0.96±0.04, shNF1=0.71±0.02, P<0.05) on the shNF1 Schwann cell model than the classic MEK1/2 inhibitor selumetinib (IC50: NC=14.36±0.95, shNF1=24.83±0.98, P>0.05). For in vivo inhibition, the CA3 group and the selumetinib group displayed a similar inhibition effect with no significant difference. Increased nuclear translation and the functional state of YAP implies that the YAP-Hippo pathway might play an important role in the formation and remyelination of pNF. Compared with selumetinib, the YAP inhibitor can exhibit a similar but more sensitive effect on NF1-/- Schwann cells. These observations imply that YAP as a novel or adjuvant therapy target in the treatment of pNF.

Association between acculturation and metabolic syndrome in Hispanic adults mediated by fruits intake.

OBJECTIVES: Hispanic adults in the USA tend to have a disproportionate prevalence of metabolic syndrome (MetS) as compared to other races. DESIGN: We examined whether the association between acculturation and MetS and its components are mediated by the intake of fruit in Hispanics. SETTING: Data from the National Health and Nutrition Examination Surveys 2009-2016 were used in this study. PARTICIPANTS: A total of 2078 Hispanics aged ≥ 20 years were included in this analysis. RESULTS: The mediating role of total fruit intake was assessed using multivariable-adjusted logistic structural equation models with the bootstrapping method by estimating indirect (IE) and direct (DE) effects from acculturation to MetS. High acculturation was associated with increased odds of MetS (adjusted OR = 1·20, 95 % CI 1·04, 1·39), central obesity (OR = 1·24, 95 % CI 1·07, 1·44) and high blood pressure (OR = 1·16, 95 % CI 1·02, 1·32) among Hispanic adults. Total fruits intake partially mediated the associations of acculturation with MetS (ORIE = 1·02, 95 % CI 1·00, 1·03) and central obesity (ORIE = 1·02, 95 % CI 1·00, 1·03), whereas fully mediated the association between acculturation and high blood pressure (ORIE = 1·03, 95 % CI 1·01, 1·06). Moreover, intake of total fruits fully mediated the acculturation-MetS association among Mexican Americans (ORIE = 1·02, 95 % CI 1·00, 1·05). CONCLUSIONS: Our findings suggested that increasing fruit consumption may reduce the impact of high acculturation on MetS development in Hispanic adults. Further studies are needed to confirm these findings.

Feasibility study of vertical flow constructed wetland for tertiary treatment of nanosilver wastewater and temporal-spatial distribution of pollutants and microbial community.

Silver nanoparticles (AgNPs) have the potential to cause negative effects on nutrient removal in constructed wetlands (CWs), further leading to the deterioration of the water. The current work aimed to investigate the feasibility of vertical flow CW (VFCW) for tertiary treatment of AgNPs wastewater, temporal-spatial distribution of pollutants, and microbial community after 450-day exposure. Results reveal that the effluent of VFCW could still meet the discharge limits except the slightly excessive concentration of phosphorus (>0.5 mg/L) from day 390, with the average removal efficiencies of 83%, 61%, 42%, 70%, and 66% for the chemical oxygen demand, total nitrogen, ammonia nitrogen, total phosphorus, and soluble orthophosphate during 450 days, respectively. Results show that AgNPs removal was relatively stable over time, up to 96%. The temporal-spatial analysis reveals that all contaminants were mainly retained in the soil layer. The Ag concentrations in the upper soil layer and plant roots were higher than that in the lower soil layer and plant stems and leaves, respectively. Microbial sequencing analysis reveals the significant differences in the microbial community at different depths on day 450, with the dominant phyla of Proteobacteria, Acidobacteria, Chloroflexi and Bacteroidetes, and dominant genera of Halomonas and Pseudomonas. These results provide much needed knowledge for the implementation of ecological technologies for AgNPs and nutrient removal simultaneously.

Precise Identification and Analysis of Micro/Nano-Sized Pore Structure in Shale with Fe3O4/Au Hybrid Nanocomposite.

Analysis and characterization of micro/nano-sized pore structure are critical issues in shale geology and engineering. Scanning electron microscopy (SEM) imaging is one of the most widespread methods for the analysis of the micro/nano-sized pores in shale, but precise identification of the ultrafine pore structure in shale is still a big challenge because shale is so complex that some components may have overlap with pores based on the simple discrimination of gray scale under SEM microscopy. Here, Fe3O4/Au nanocomposite with magnetic properties is synthesized, characterized, and introduced as a novel pore-marker to improve SEM identification and quantitation of micro/nano-sized pores in shale. Due to the superparamagnetic property, the nanomarker is conveniently controlled by an external magnetic field to fill into pores and offers a sharp contrast imaging between matrix of shale (various gray) and pores (bright), which makes the identification of micro/nano-sized pores in shale much more straightforward and reliable. Furthermore, because gold, as a noble metal, is particularly rare in shale, energy-dispersive X-ray spectroscopy mapping of Au is delicately used to precisely calculate area porosity in shale. Combining with the aforementioned merits of the nanomarker, a precise and practical technique is proposed to promote characterization of micro/nano-sized pores in shale.

Reversible Band Gap Narrowing of Sn-Based Hybrid Perovskite Single Crystal with Excellent Phase Stability.

An intriguing reversible band gap narrowing behavior of the lead-free hybrid perovskite single crystal DMASnI3 (DMA=CH3 NH2 CH3 + ) from yellow to black is observed without phase transformation. We discuss the transformation mechanism in detail. More interestingly, the transformed samples in black can rapidly self-heal into yellow ones when exposed to deionized water (DI water). Contrary to other hybrid perovskites, DMASnI3 crystals exhibit excellent water phase stability. For example, DMASnI3 was immersed in DI water for 16 h and no decomposition was observed. Inspired by its excellent water phase stability, we demonstrate a potential eco-friendly application of DMASnI3 in photo-catalysis for H2 evolution in DI water. We present the first H2 evolution rate of 0.64 µmol h-1 with good recycling properties for pure DMASnI3 crystals. After the narrowing process, the optical band gap of DMASnI3 can be lowered from 2.48 eV to 1.32 eV. Systematical characterizations are applied to investigate their structures and optoelectronic properties. The reversible band gap narrowing behavior and outstanding electrical properties, such as higher carrier mobility and long carrier lifetime show that DMASnI3 has a great potential for optoelectronic applications.

Hepatitis due to Reactivation of Hepatitis B Virus in Endemic Areas Among Patients With Hepatitis C Treated With Direct-acting Antiviral Agents.

Hepatitis due to reactivation of hepatitis B virus (HBV) has been reported in patients treated with direct-acting antiviral (DAA) agents for chronic hepatitis C virus infection. We performed an observational study to determine the incidence of and factors associated with hepatitis in 327 patients receiving pan-oral DAA agents for HCV infections in areas endemic for HBV in China. Ten patients were positive for hepatitis B surface antigen (HBsAg), and 124 patients had occult HBV infection. HBV reactivation was determined by measuring HBV DNA and HBsAg status in serial serum samples collected every 2 weeks during DAA treatment and then every 4 weeks after treatment until week 12. In the total study population, 10 patients (3.1%) had hepatitis; 3 cases were associated with HBV reactivation (1 case not in the icteric phase, 1 case in the icteric phase, and 1 case with liver failure) and 7 from other causes. Testing positive for HBsAg before DAA treatment was a strong risk factor for developing hepatitis during treatment (hazard ratio, 15.0; P < .001).

Imaging the Pore Structure of Geological Materials with Bifunctional Nanoparticles.

Analysis of complex pore structure of geomaterials is a fundamental issue in geoscience. Here bifunctional nanoparticles with magnetic and fluorescent properties are introduced as novel markers for optical imaging of pore structure in geomaterials. Using the paramagnetic property, powder of the nanoparticle is driven into pores under an external magnetic field, avoiding a tedious sample preparation and eliminating artificial damage of sample preparation in conventional methods. Meanwhile, the fluorescent nanoparticle marker offers a sharp contrast imaging between the rock matrix (black) and pores (bright) under microscopy. Furthermore, fluorescent nanoparticles with different sizes and colors are designed to demonstrate the potential of the method for describing pore throat sizes. Combining the merits of the paramagnetic and fluorescent properties of nanoparticles, a convenient and practical sample preparation is proposed to promote optical imaging analysis of the pore structure in geomaterials.