Assembly of Functional Co(II) Metal-Organic Frameworks through a Mixed Ligand Strategy: Structure and Photocatalytic Degradation Properties.

Four Co(II)-based metal-organic frameworks (MOFs) were constructed by a mixed ligand strategy under solvothermal conditions. The controllable modification of the bridging groups in the secondary building units was realized by changing the anions in MOFs 1-3. The MOF 4 with 3D framework structure was obtained by regulating the solvent ratio following the synthesis process of MOF 3. Furthermore, the MOFs 1-4 exhibited efficient photocatalytic activity for the degradation of malachite green (MG) dye without any photosensitizer or cocatalyst under a low-energy light source, the decolorization ratio of MG all reached more than 96.0% within 60 min, and maximal degradation was obtained to be 99.4% (MOF 4). The recycling experiments showed that the degradation rate of MG was still higher than 91% after 10 cycles. In the MOF 4 as representation, the photocatalytic process was explored systematically. The possible mechanism of catalytic degradation was discussed, which proved the existence of efficient oxidation active factors (•O2-, •OH, and h+). The possible intermediates and degradation pathways were investigated based on high-performance liquid chromatography tandem mass spectrometry. Additionally, MOFs 1-4 also exhibited excellent photocatalytic activity for the degradation of methylene blue, methyl violet, rhodamine B, and basic red 9.

Two 2D Metal-Organic Frameworks Based on Purine Carboxylic Acid Ligands for Photocatalytic Oxidation of Sulfides and CO2 Chemical Fixation.

Two two-dimensional (2D) layered metal-organic frameworks (MOFs), namely, {[Yb(L)(H2O)2NO3]·2H2O}n (Yb-MOF) and [Er(L)(H2O)3Cl]n (Er-MOF) (H2L = 5-((6H-purin-6-yl)amino)isophthalic acid), were constructed by a solvothermal method and characterized. The catalytic performance study showed that the Yb-MOF could efficiently catalyze the oxidation of sulfides to sulfoxides under 15 W light-emitting diode (LED) blue light irradiation. Electron paramagnetic resonance spectroscopy and free-radical trapping experiments demonstrated that the photocatalytic reaction process involved •O2-, and the corresponding mechanism was proposed. Moreover, Er-MOF exhibited good catalytic efficiency and excellent substrate tolerance in the cycloaddition reaction of CO2, and the reaction conditions were mild. After 5 cycles, the catalytic activities of two MOFs did not significantly decrease, and the framework structures remained unchanged. Therefore, the Yb-MOF and Er-MOF were considered efficient and stable heterogeneous catalysts.

Synergistic Enzyme-Mimetic Catalysis-Based Non-Thermal Sonocavitation and Sonodynamic Therapy for Efficient Hypoxia Relief and Cancer Ablation.

Non-invasive cancer treatment strategies that enable local non-thermal ablation, hypoxia relief, and reactive oxygen species (ROS) production to achieve transiently destroying tumor tissue and long-term killing tumor cells would greatly facilitate their clinical applications. However, continuously generating oxygen cavitation nuclei, reducing the transient cavitation sound intensity threshold, relieving hypoxia, and improving its controllability in the ablation area still remains a significant challenge. Here, in this work, an Mn-coordinated polyphthalocyanine sonocavitation agent (Mn-SCA) with large d-π-conjugated network and atomic Mn-N sites is identified for the non-thermal sonocavitation and sonodynamic therapy in the liver cancer ablation. In the tumor microenvironment, the catalytical generation of oxygen assists cavitation formation and generates microjets to ablate liver cancer tissue and relieve hypoxia, this work reports for the first time to utilize the enzymatic properties of Mn-SCA to lower the cavitation threshold in situ. Moreover, under pHIFU irradiation, high reactive oxygen species (ROS) production can be achieved. The two merits in liver cancer ablation are demonstrated by cell destruction and high tumor inhibition efficiency. This work will help deepen the understanding of cavitation ablation and the sonodynamic mechanisms related to the nanostructures and guide the design of sonocavitation agents with high ROS production for solid tumor ablation.

Structure optimization of heterogeneous compound eye camera for improving the detection performance.

To achieve fast location, precise tracking and accurate identification over a large field of view (FOV), we have proposed a heterogeneous compound eye camera (HeCECam), which consists of a heterogeneous compound eye array, an optical relay system and a CMOS detector. However, the current HeCECam can hardly acquire high-precision 3D information of the targets to realize these applications. To solve this challenge, we propose a scheme on optimizing the structure of the HeCECam to improving the detection performance, including the optimization of the distribution uniformity of the sub-eyes with the proposed "Three-direction center-of-gravity subdivision (TGS)" and the enhancement of the compatibility between heterogeneous compound eyes and the optical relay system with the proposed compensation method for tilt. The TGS significantly reduces the distribution unevenness of sub-eyes down to 117% from the previous 152%, and provides symmetry to the heterogeneous compound eye array. The tilt compensation effectively addresses previous imaging defects, such as distortion of sub-images, increased stray light, and support structures being imaged, and it improves the imaging clarity of the system, especially in external FOV. Based on two proposed methods, we re-design and fabricate the heterogeneous compound eye array to obtain a high-performance prototype. To verify the imaging capacities of the optimized HeCECam, a series of comparison experiments are performed, including blank scene imaging, FOV tests, resolution verification and real-world scene imaging. The results show that the previous imaging defects have been well eliminated, and the optimized prototype has stronger resolving power and wider FOV. This allow the HeCECam to perform better in subsequent practical applications, such as wide-area surveillance, forewarning, and navigation.

Masking effects on iso-valeric acid recognition by sub-threshold odor mixture.

Masking unpleasant odors with pleasant-smelling odorants has a long history and is utilized in various industries, including perfumery and consumer products. However, the effectiveness of odor masking is idiosyncratic and temporary. In this study, we employed Sniff olfactometry (SO) to investigate the psychophysics of masking using brief 70 ms stimulations with mixtures of the mal-odorant iso-valeric acid (IVA) and different masking agents. IVA is a component of human sweat that can overpower its smell and is often associated with unpleasant descriptors such as "gym locker," "smelly feet," "dirty clothes," and so on. Traditionally, high concentrations of pleasant-smelling odorants are used to mitigate the unpleasantness of IVA in situations involving clothing or environments contaminated with IVA. To examine the masking effects of sub-threshold levels of various masking agents (neohivernal, geraniol, florhydral, decanal, iso-longifolanone, methyl iso-eugenol, and s-limonene) on IVA, we conducted experiments using SO to measure the probability of recognizing IVA after 70 ms stimulations with headspaces containing mixtures of super-threshold concentrations of IVA and sub-threshold concentrations of IVA suppressors. The study involved nine subjects, and on average, a single masking agent was found to decrease IVA recognition probability by 14-72%. Moreover, a sub-threshold odor mixture consisting of 6 masking agents demonstrated a substantial decrease in IVA recognition, with a reduction of 96%.

Degradation of Diclofenac by Loaded Solid Superbase-Activated Persulfate.

Alkali-activated persulfate (PS) is widely used in situ in chemical oxidation processes; however, studies on the innovation of the alkali activation process are very limited. Two supported solid superbases, namely KNO3/γ-Al2O3 (KAl) and KNO3/SBA-15/MgO (KSM), respectively, were prepared and used to activate persulfate to degrade DCF in this work. The results showed that the superbases elevated the solution pH once added and thus could catalyze persulfate to degrade diclofenac efficiently above pH 10.5. The catalytic efficiency of KAl was close to that of sodium hydroxide, and that of KSM was the highest. The mechanism might be that, in addition to raising the solution pH, some potassium existed as K2O2, which had a strong oxidizing effect and was conducive to DCF removal. Hydroxyl, sulfate and superoxide radicals were all found in the reaction system, among which hydroxyl might play the most important role. The material composition ratio, common anion and humic acid all had some influences on the catalytic efficiency. A total of five intermediates were found in the KSM/PS oxidation system, and six oxidation pathways, which were hydroxylation, dehydrogen, dechlorination, dehydration, decarboxylation, and C-N bond breakage, might be involved in the reaction process. Several highly toxic oxidation products that should be paid attention to were also proposed.

The recombinant pseudorabies virus expressing porcine deltacoronavirus spike protein is safe and effective for mice.

BACKGROUND: Porcine deltacoronavirus (PDCoV) is a new pathogenic porcine intestinal coronavirus, which has appeared in many countries since 2012. PDCoV disease caused acute diarrhea, vomiting, dehydration and death in piglets, resulted in significant economic loss to the pig industry. However, there is no commercially available vaccine for PDCoV. In this study, we constructed recombinant pseudorabies virus (rPRVXJ-delgE/gI/TK-S) expressing PDCoV spike (S) protein and evaluated its safety and immunogenicity in mice. RESULTS: The recombinant strain rPRVXJ-delgE/gI/TK-S obtained by CRISPR/Cas gE gene editing technology and homologous recombination technology has genetic stability in baby hamster syrian kidney-21 (BHK-21) cells and is safe to mice. After immunizing mice with rPRVXJ-delgE/gI/TK-S, the expression levels of IFN-γ and IL-4 in peripheral blood of mice were up-regulated, the proliferation of spleen-specific T lymphocytes and the percentage of CD4+ and CD8+ lymphocytes in mice spleen was increased. rPRVXJ-delgE/gI/TK-S showed good immunogenicity for mice. On the seventh day after booster immunity, PRV gB and PDCoV S specific antibodies were detected in mice, and the antibody level continued to increase, and the neutralizing antibody level reached the maximum at 28 days post- immunization (dpi). The recombinant strain can protect mice with 100% from the challenge of virulent strain (PRV XJ) and accelerate the detoxification of PDCoV in mice. CONCLUSION: The recombinant rPRVXJ-delgE/gI/TK-S strain is safe and effective with strong immunogenicity and is expected to be a candidate vaccine against PDCoV and PRV.

[Fucoidan-Modified Phase-Transitional Contrast Agent for Ultrasound Imaging and Targeting of Hepatoma Cells].

Objective: To prepare a fucoidan-modified phase-transitional contrast agent (FPCA) and to evaluate its in vitro capabilities for ultrasound imaging and targeting of hepatoma cells. Methods: Nano-liposomes encapsulated with perfluoropentane were prepared using thin-film hydration and ultrasonic emulsification methods. Then, FPCA nanoparticles were prepared through chemical grafting of fucoidan and the characterization of their physical and chemical properties was performed. After applying external stimuli of heating with hot water bath and microwave irradiation, the phase-transition status of FPCA was observed with microscope. The imaging abilities of phase-transited FPCA on two-dimensional ultrasound and contrast-enhanced ultrasound were observed with ultrasonic diagnostic instrument. The ability of FPCA to target at hepatoma cells was evaluated and verified with fluorescence confocal observation and flow cytometry analysis. Results: The FPCA prepared in the study had an average diameter of (222.1±32.5) nm, displaying spherical appearance, good dispersion, good stability, and good biocompatibility. The phase-transition of FPCA was induced by both heating with hot water bath and microwave irradiation. For phase transition, the optimal temperature was found to be 50 ℃ and the preferred microwave power was 1.5 W/cm 2. Moreover, after phase transition, FPCA showed significant imaging enhancement on both two-dimensional ultrasonography and contrast-enhanced ultrasonography. Through fluorescein isothiocyanate (FITC) labeling, FPCA could specifically bind with hepatoma cells at a high binding rate of (96.19±1.62)%, while it rarely bound with normal liver cells, showing a binding rate of less than 10%. Conclusion: A new type of phase-transitional ultrasound contrast agent with good stability and biocompatibility was successfully prepared. It not only could enhance ultrasound imaging through phase transition, but also had specific active hepatoma cell-targeting properties.

The extracellular sulfatase SULF2 promotes liver tumorigenesis by stimulating assembly of a promoter-looping GLI1-STAT3 transcriptional complex.

The expression of the extracellular sulfatase SULF2 has been associated with increased hepatocellular carcinoma (HCC) growth and poor patient survival. However, the molecular mechanisms underlying SULF2-associated tumor growth remain unclear. To address this gap, here we developed a transgenic mouse overexpressing Sulf2 in hepatocytes under the control of the transthyretin promoter. In this model, Sulf2 overexpression potentiated diethylnitrosamine-induced HCC. Further analysis indicated that the transcription factor GLI family zinc finger 1 (GLI1) mediates Sulf2 expression during HCC development. A cross of the Sulf2-overexpressing with Gli1-knockout mice revealed that Gli1 inactivation impairs SULF2-induced HCC. Transcriptomic analysis revealed that Sulf2 overexpression is associated with signal transducer and activator of transcription 3 (STAT3)-specific gene signatures. Interestingly, the Gli1 knockout abrogated SULF2-mediated induction of several STAT3 target genes, including suppressor of cytokine signaling 2/3 (Socs2/3); Pim-1 proto-oncogene, Ser/Thr kinase (Pim1); and Fms-related tyrosine kinase 4 (Flt4). Human orthologs were similarly regulated by SULF2, dependent on intact GLI1 and STAT3 functions in HCC cells. SULF2 overexpression promoted a GLI1-STAT3 interaction and increased GLI1 and STAT3 enrichment at the promoters of their target genes. Interestingly, the SULF2 overexpression resulted in GLI1 enrichment at select STAT3 consensus sites, and vice versa. siRNA-mediated STAT3 or GLI1 knockdown reduced promoter binding of GLI1 and STAT3, respectively. Finally, chromatin-capture PCR confirmed long-range co-regulation of SOCS2 and FLT3 through changes in promoter conformation. These findings define a mechanism whereby SULF2 drives HCC by stimulating formation of a GLI1-STAT3 transcriptional complex.

Mechanical ventilation parameters in critically ill COVID-19 patients: a scoping review.

BACKGROUND: The mortality of critically ill patients with COVID-19 is high, particularly among those receiving mechanical ventilation (MV). Despite the high number of patients treated worldwide, data on respiratory mechanics are currently scarce and the optimal setting of MV remains to be defined. This scoping review aims to provide an overview of available data about respiratory mechanics, gas exchange and MV settings in patients admitted to intensive care units (ICUs) for COVID-19-associated acute respiratory failure, and to identify knowledge gaps. MAIN TEXT: PubMed, EMBASE, and MEDLINE databases were searched from inception to October 30, 2020 for studies providing at least one ventilatory parameter collected within 24 h from the ICU admission. The quality of the studies was independently assessed using the Newcastle-Ottawa Quality Assessment Form for Cohort Studies. A total of 26 studies were included for a total of 14,075 patients. At ICU admission, positive end expiratory pressure (PEEP) values ranged from 9 to 16.5 cm of water (cmH2O), suggesting that high levels of PEEP were commonly used for setting MV for these patients. Patients with COVID-19 are severely hypoxemic at ICU admission and show a median ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ranging from 102 to 198 mmHg. Static respiratory system compliance (Crs) values at ICU admission were highly heterogenous, ranging between 24 and 49 ml/cmH2O. Prone positioning and neuromuscular blocking agents were widely used, ranging from 17 to 81 and 22 to 88%, respectively; both rates were higher than previously reported in patients with "classical" acute respiratory distress syndrome (ARDS). CONCLUSIONS: Available data show that, in mechanically ventilated patients with COVID-19, respiratory mechanics and MV settings within 24 h from ICU admission are heterogeneous but similar to those reported for "classical" ARDS. However, to date, complete data regarding mechanical properties of respiratory system, optimal setting of MV and the role of rescue treatments for refractory hypoxemia are still lacking in the medical literature.

[Study on anti-hyperlipidemia effect of Linderae Radix via regulating reverse cholesterol transport].

This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.

Efficacy, metabolism and pharmacokinetics of Ro 15-5458, a forgotten schistosomicidal 9-acridanone hydrazone.

BACKGROUND: Treatment of schistosomiasis, a neglected disease, relies on just one partially effective drug, praziquantel. We revisited the 9-acridanone hydrazone, Ro 15-5458, a largely forgotten antischistosomal lead compound. METHODS: Ro 15-5458 was evaluated in juvenile and adult Schistosoma mansoni-infected mice. We studied dose-response, hepatic shift and stage specificity. The metabolic stability of Ro 15-5458 was measured in the presence of human and mouse liver microsomes, and human hepatocytes; the latter also served to identify metabolites. Pharmacokinetic parameters were measured in naive mice. The efficacy of Ro 15-5458 was also assessed in S. haematobium-infected hamsters and S. japonicum-infected mice. RESULTS: Ro 15-5458 had single-dose ED50 values of 15 and 5.3 mg/kg in mice harbouring juvenile and adult S. mansoni infections, respectively. An ED50 value of 17 mg/kg was measured in S. haematobium-infected hamsters; however, the compound was inactive at up to 100 mg/kg in S. japonicum-infected mice. The drug-induced hepatic shift occurred between 48 and 66 h post treatment. A single oral dose of 50 mg/kg of Ro 15-5458 had high activity against all tested S. mansoni stages (1-, 7-, 14-, 21- and 49-day-old). In vitro, human hepatocytes produced N-desethyl and glucuronide metabolites; otherwise Ro 15-5458 was metabolically stable in the presence of microsomes or whole hepatocytes. The maximum plasma concentration was approximately 8.13 µg/mL 3 h after a 50 mg/kg oral dose and the half-life was approximately 4.9 h. CONCLUSIONS: Ro 15-5458 has high activity against S. mansoni and S. haematobium, yet lacks activity against S. japonicum, which is striking. This will require further investigation, as a broad-spectrum antischistosomal drug is desirable.

Isolation and phylogenomic analysis of two Senecavirus A isolates in Sichuan Province, 2018.

In our study, we isolated and characterised two new Senecavirus A (SVA) isolates in Sichuan Province, China. Phylogenetic analysis of both the SVA full-length genomes and the VP1 genes revealed that the two new SVA isolates are more closely related to previous Chinese strains and US strains. The most variable isolate, SVV-SC-01, showed a significant difference from previous SVA strains, and it was identified as a recombinant using several algorithms. Study findings indicate that the SVA virus in China is constantly evolving and new SVA variants may have emerged. Hence, we must take effective measures to prevent further spread of SVA. This report provides evidence that SVA infection of pigs has occurred in Sichuan Province, and the results will contribute to our understanding of the genetic characteristics and recombinant events of SVA in China.

Porcine interferon lambda 3 (IFN-λ3) shows potent anti-PRRSV activity in primary porcine alveolar macrophages (PAMs).

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a serious viral disease of swine. At present, there are vaccines for the control of PRRSV infection, but the effect is not satisfactory. The recombination of attenuated vaccines causes significant difficulties with the prevention and control of PRRSV. Type III interferons (IFNs), also called IFN-λs, were newly identified and showed potent antiviral activity within the mucosal surface and immune organs. RESULTS: Therefore, primary porcine alveolar macrophages (PAMs) were used for this investigation. To this end, we found that the replication of PRRSV in PAMs was significantly reduced after pre-treatment with IFN-λ3, and such inhibition was dose- and time-dependent. The plaque formation of PRRSV abrogated entirely, and virus yields were reduced by four orders of magnitude when the primary PAMs were treated with IFN-λ3 at 1000 ng/ml. In addition, IFN-λ3 in our study was able to induce the expression of interferon-stimulated genes 15 (ISG15), 2'-5'-oligoadenylate synthase 1 (OAS1), IFN-inducible transmembrane 3 (IFITM3), and myxoma resistance protein 1(Mx1) in primary PAMs. CONCLUSIONS: IFN-λ3 had antiviral activity against PRRSV and can stimulate the expression of pivotal interferon-stimulated genes (ISGs), i.e., ISG15, Mx1, OAS1, and IFITM3. So, IFN-λ3 may serve as a useful antiviral agent.

Reliability of Transient Elastography-Based Liver Stiffness for Diagnosing Portal Hypertension in Patients with Alcoholic Liver Disease: A Diagnostic Meta-Analysis with Specific Cut-Off Values.

BACKGROUND: Transient elastography-based liver stiffness value (TE-LSV) has been studied for the diagnosis of portal hypertension. Liver stiffness is influenced by the disease etiology. We aimed to perform a meta-analysis to determine the performance of TE-LSV for diagnosing portal hypertension in patients with alcoholic liver disease (ALD). METHODS: We searched PubMed, Web of Science, Ovid and Cochrane library. A bivariate model was used to compute sensitivity and specificity. A random effects model was used to pool diagnostic odds ratios. RESULTS: 9 studies with 679 patients were included. The pooled sensitivity and specificity based on a cut-off value around 21.8 kPa for clinically significant portal hypertension (CSPH) were 0.89 (95 % confidence interval (CI), 0.83-0.93) and 0.71(95 % CI, 0.64-0.78), respectively. For severe portal hypertension (SPH), the pooled sensitivity and specificity for a cut-off value around 29.1 kPa were 0.88 (95 % CI, 0.83-0.92) and 0.74 (95 % CI, 0.67-0.81), respectively. CONCLUSION: TE-LSV showed good performance for diagnosing portal hypertension in patients with ALD. The optimal cut-off value for CSPH and SPH was around 21.8 kPa and 29.1 kPa, respectively, and these two cut-off values showed good sensitivity and modest specificity. The etiology should be clear before using TE-LSV for portal hypertension.

Metal-Organic-Framework-Derived 2D Carbon Nanosheets for Localized Multiple Bacterial Eradication and Augmented Anti-infective Therapy.

Recently emerging graphene-based 2D nanoplatforms with multiple therapeutic modalities provide enormous opportunities to combat pathogenic bacterial infections. However, because these materials suffer from complicated synthesis, massive dosage requirements, and abundant nonlocalized heat, much more simplified, tunable, and localized eradication approaches are urgently required. Herein, we report on the fabrication of the metal-organic-framework (MOF)-derived 2D carbon nanosheets (2D-CNs) with phase-to-size transformation and localized bacterial eradication capabilities for augmented anti-infective therapy. The MOF-derived, ZnO-doped carbon on graphene (ZnO@G) is first synthesized and then anchored with phase transformable thermally responsive brushes (TRB) by in situ polymerization to yield the TRB-ZnO@G. The TRB-ZnO@G exhibits flexible 2D nanostructures, high photothermal activities, sustained Zn2+ ions release, and ON-OFF switchable phase-to-size transformation abilities. Notably, the near-infrared-triggered formation of TRB-ZnO@G-bacteria aggregations enables localized massive Zn2+ ions penetration, physical cutting, and hyperthermia killing, which synergistically enhance the disruption of bacterial membranes and intracellular substances. The obtained novel 2D-CNs not only present robust and localized multiple bacterial eradication capabilities with nearly 100% bactericidal efficiency at low concentrations but also possess rapid and safe skin wound disinfection via a short-time photothermal treatment without damaging normal skin tissues or causing accumulative toxicities, thus presenting great potential for broad-spectrum eradication of pathogenic bacteria.

Exploring the tissue tropism of pseudorabies virus based on miRNA level analysis.

BACKGROUND: Pseudorabies virus (PRV, or suid herpesvirus, SuHV-1), a member of the herpesvirus family, has an extremely broad host range and threatens the pig industry in China. PRV can evade host innate immunity and infect the kidney, lung, brain and other tissues. At the same time, many studies have reported that microRNA (miRNA) can affect the replication of viruses by regulating gene expression levels. RESULTS: Here, to identify changes in miRNA expression and post-transcriptional regulation associated with PRV infection in the lung, spleen, and olfactory bulb, we sequenced small RNAs in tissues of rats infected or uninfected with PRV strain XJ (PRV-XJ). Sixty-one, 199 and 29 differentially-expressed miRNAs were identified in the lung, spleen, and olfactory bulb, respectively, of infected compared with uninfected rats. Among the miRNAs differentially-expressed in PRV-infected rats, 36, 171, and 15 miRNAs showed tissue-selective expression in the olfactory bulb, lung and spleen, respectively. All differentially-expressed miRNAs were analyzed for their GO functional annotations and KEGG pathway associations . CONCLUSIONS: In PRV-XJ-infected rats, miRNAs were differentially expressed in the lung, spleen and olfactory bulb. These miRNAs were involved in regulating various pathways of the nervous, respiratory and immune systems, and may affect the tissue tropism of the virus and play pivotal roles in viral infection and proliferation.

Novel TRRAP mutation causes autosomal dominant non-syndromic hearing loss.

Hereditary non-syndromic hearing loss is the most common inherited sensory defect in humans. More than 40 genes have been identified as causative genes for autosomal dominant non-syndromic hearing loss (ADNSHL), but there are many other candidate genes that remain to be discovered. We aimed to identify the causative gene mutation for post-lingual progressive ADNSHL in a Chinese family. Whole-exome sequencing, bioinformatic analysis, and Sanger sequencing were used to verify the co-segregation of a novel pathogenic variant (NM_ 001244580, c.511C>T, p.Arg171Cys) in the TRansformation/tRanscription domain-Associated Protein gene associated with hearing loss in a three-generation Chinese family with ADNSHL). Additionally, three more novel variants of transformation/transcription domain associated protein (TRRAP) were detected in 66 sporadic cases of hearing loss. Morpholino oligonucleotides knockdown and clustered regularly interspaced short palindromic repeats/Cas9 knockout zebrafish were constructed to validate the genetic findings. Knockdown or knockout of TRRAP resulted in significant defects in the inner ear of zebrafish, indicating that TRRAP plays an important role in inner ear development. In conclusion, TRRAP (NM_ 001244580, c.511C>T, p.Arg171Cys) co-segregated with hearing loss in a Chinese family with ADNSHL, and TRRAP deficiency caused hearing disability in zebrafish, suggesting TRRAP is a gene associated with ADNSHL.

Specific prognostic factors in hepatitis B virus-related and non-hepatitis B virus-related intrahepatic cholangiocarcinoma after macroscopic curative resection.

BACKGROUND: The hepatitis B virus (HBV)-related intrahepatic cholangiocarcinoma (iCCA) was recognized as a unique subtype of iCCA, within particular features in demography, clinicopathology, and genealogy. However, how they predict prognosis, in particular, for HBV- and non-HBV-related iCCA is still unclear. METHODS: Demographic, clinicopathologic, and genetic features were retrospectively collected and reviewed to determine the specific prognostic factors, precisely predicting the overall survival (OS) in HBV-related (n = 119) and non-HBV-related ( n = 149) iCCA patients, respectively. RESULTS: In HBV-related iCCA, TP53 mutation, vascular invasion, extrahepatic metastasis, and serum levels of alpha-fetoprotein (AFP) were independent prognostic factors for OS. In non-HBV-related iCCA, RAS/ RAF mutation and lymphatic metastasis independently predicted the OS of patients. Tumor differentiation and serum levels of CA19-9 were significantly associated with OS in both HBV- and non-HBV-related iCCA patients. In a subset analysis, TP53 and RAS/RAF mutations were consistently related to poorer outcome in HBV- and non-HBV-related iCCA, respectively. CONCLUSIONS: The HBV- and non-HBV-related iCCA have different prognostic factors for the OS.

Epigenetic regulation of megakaryocytic and erythroid differentiation by PHF2 histone demethylase.

Plant homeodomain finger 2 (PHF2) is a JmjC family histone demethylase that demethylates H3K9me2, a repressive gene marker. PHF2 was found to play a role in the differentiation of several tissue types such as osteoblast and adipocyte differentiation. We report here that PHF2 plays a role in the epigenetic regulation of megakaryocytic (MK) and erythroid differentiation. We investigated PHF2 expression during MK and erythroid differentiation in K562 and human CD34+ progenitor (hCD34+ ) cells. Our data demonstrate that PHF2 expression is down-regulated during megakaryopoiesis and erythropoiesis. PHF2 has a negative role in MK and erythroid differentiation of K562 cells; knockdown of PHF2 promotes MK and erythroid differentiation of hCD34+ cells. Similarly, we found that p53 expression is also down-regulated during MK and erythroid differentiation, which parallels PHF2 expression. PHF2 binds to the p53 promoter and regulates the expression of p53 by demethylating H3K9me2 in the promoter region of p53. Taken together, our data show that PHF2 is a negative epigenetic regulator of MK and erythroid differentiation, and that one of the pathways through which PHF2 affects MK and erythroid differentiation is via regulation of p53 expression.