Immediate and delayed effects of environmental temperature on schizophrenia admissions in Liuzhou, China, 2013-2020: a time series analysis.

This study aimed to investigate the associations between environmental temperature and schizophrenia admissions in Liuzhou, China. A Poisson generalized linear model combined with a distributed lag nonlinear model was used to analyze the effects of daily mean temperature on schizophrenia admissions from 2013 to 2020 in Liuzhou. Additionally, subgroup analyses were conducted to investigate possible modifications stratified by gender, marital status, and age. In this study, 10,420 schizophrenia admissions were included. The relative risks of schizophrenia admissions increased as the temperature rose, and the lag effects of high temperature on schizophrenia admissions were observed when the daily mean temperature reached 21.65°C. The largest single effect was observed at lag0, while the largest cumulative effect was observed at lag6. The single effects of high temperatures on schizophrenia admissions were statistically significant in both males and females, but the cumulative effects were statistically significant only in males, with the greatest effect at lag0-7. The single effect of high temperatures on admissions for unmarried schizophrenics was greatest at lag5, while the maximum cumulative effect for unmarried schizophrenia was observed at lag0-7. The single effects of high temperatures on schizophrenia admissions were observed in those aged 0-20, 21-40, and 41-60. The cumulative effects for schizophrenics aged 21-40 were observed from lag0-3 to lag0-7, with the maximum effect at lag0-7. In conclusion, the risk of schizophrenia admissions increased as the environmental temperature increased. The schizophrenics who were unmarried appeared to be more vulnerable to the single and cumulative effects of high temperature.

Identification of potential core genes in pseudoexfoliation using bioinformatics analysis and retrospective analysis of 84 patients with this disease.

BACKGROUND: Pseudoexfoliation (XFS) is a common cause of glaucoma in nowadays. Because of XFS causing irreversible blindness secondary to glaucoma (XFG), this study aims to identify the current prevalence of XFS among Xinjiang Province of China, and identify the hub genes involved in XFS. METHODS: A retrospective chart review was conducted from 2007 to 2019 for patients aged 50 and older. All patients with XFS or XFG diagnosed by slit lamp exam were identified through chart review. RESULTS: Of the 84 patient charts available for review, 50% of the patients identified as male, with a mean age of 67 years. The top ten genes evaluated by connectivity degree in the PPI network were identified. The results showed that Tyrobp was the most outstanding gene, followed by Ptprc, Fcgr3, Itgb2, Emr1, Cd68, Syk, Fcerlg, Hck, and Lyz2. All of these hub genes were downregulated in XFS. CONCLUSION: Our findings show a considerably biomarkers of XFS for diagnosis and treatment.

Endocarditis due to Aggregatibacter Segnis: a rare case report.

BACKGROUND: As a member of the HACEK group, Aggregatibacter segnis (A. segnis) is a fastidious Gram-negative coccobacillus that resides in the human oropharyngeal flora. Infective endocarditis caused by A. segnis is rarely reported. CASE PRESENTATION: A 31-year-old male was admitted to our hospital for a 3-month history of intermittent high fever, chills, and chest distress. On presentation, he was febrile and tachycardic but otherwise with stable vital signs. Physical examination revealed systolic murmurs in the aortic and mitral valve areas. Pitting edema was evident in the lower extremities. Transthoracic echocardiography demonstrated multiple vegetations in the mitral and aortic valves. Severe regurgitation of the aortic valve and left heart dysfunction were also detected. With the suspicion of infective endocarditis and heart failure, we immediately performed microbiological tests and arranged the cardiac replacement surgery. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and metagenomic next-generation sequencing (mNGS) identified A. segnis from the bloodstream. While the surgical specimen culture was negative, the mNGS was positive for A. segnis. The patient was treated with ceftriaxone for four weeks and discharged. He remained clinically well, with laboratory results restored. CONCLUSION: This is the first report of A. segnis infective endocarditis that combined MALDI-TOF and metagenomic next-generation sequencing in the diagnosis. The hypothesis-independent molecular techniques can outperform conventional tools to prevent diagnostic delay.

Thyroid dysfunction incidence and risk factors in Chinese chronic hepatitis B patients treated with pegylated interferon alpha: A long-term follow-up study.

The long-term impact, incidence and risk factors of thyroid dysfunction in chronic hepatitis B (CHB) patients receiving pegylated interferon (IFN) alpha (PegIFN-alpha) therapy remain unclear. We aim to investigate the long-term safety of thyroid dysfunction in CHB patients receiving PegIFN-alpha. A retrospective observational study of 425 CHB patients with normal baseline thyroid function was carried out. Patients were followed up over 10 years to assess thyroid function after receiving IFN. At the end of the IFN therapy, 67 patients (15.8%) had developed thyroid dysfunction, 31 patients (46.3%) had hyperthyroidism and 64.4% presented with subclinical thyroid dysfunction. In follow-up of thyroid dysfunction patients, 37 patients (74.0%) spontaneously regained normal thyroid function. Pretreatment thyroid-stimulating hormone (TSH) level, thyroid peroxidase antibody (TPOAb) positivity and free thyroxine (FT4) were independent risk factors associated with thyroid dysfunction incidence. High TSH level (OR = 9.866, 95%CI, 3.245-29.998) was associated with a greater likelihood of hypothyroidism. High FT4 levels (OR = 0.464, 95%CI, 0.248-0.868) indicate a low likelihood of thyroid dysfunction. Thyroid dysfunction is a common but acceptable side effect of IFN therapy for CHB. Most thyroid dysfunction is reversible. Pretreatment TSH level and TPOAb positivity are risk factors for thyroid dysfunction development during IFN therapy. A high TSH level predicts an increased incidence of hypothyroidism. Moreover, FT4 may be a protective factor for thyroid dysfunction.

Demography and adaptation promoting evolutionary transitions in a mammalian genus that diversified during the Pleistocene.

Species that evolved in temperate regions during the Pleistocene experienced periods of extreme climatic transitions. Consequent population fragmentation and dynamics had the potential to generate small, isolated populations where the influence of genetic drift would be expected to be strong. We use comparative genomics to assess the evolutionary influence of historical demographics and natural selection through a series of transitions associated with the formation of the genus Capreolus, speciation within this genus during the Quaternary and during divergence among European roe deer (C. capreolus) populations. Our analyses were facilitated by the generation of a new high-coverage reference genome for the Siberian roe deer (C. pygargus). We find progressive reductions in effective population size (Ne ), despite very large census sizes in modern C. capreolus populations and show that low Ne has impacted the C. capreolus genome, reducing diversity and increasing linkage disequilibrium. Even so, we find evidence for natural selection shared among C. capreolus populations, including a historically documented founder population that has been through a severe bottleneck. During each phylogenetic transition there is evidence for selection (from dN/dS and nucleotide diversity tests), including at loci associated with diapause (delayed embryonic development), a phenotype restricted to this genus among the even-toed ungulates. Together these data allow us to assess expectations for the origin and diversification of a mammalian genus during a period of extreme environmental change.

An antiviral drug-resistant mutant of hepatitis B virus with high replication capacity in association with a large in-frame deletion in the preS1 region of viral surface gene.

We amplified a full-length hepatitis B virus (HBV) genome from the serum of a chronic hepatitis B patient who experienced virological breakthrough with high HBV DNA titer following adefovir (ADV) therapy. The PCR product was cloned and sequencing of the six clones revealed an isolate of C2 subgenotype. Mutation(s) in the polymerase gene responsible for ADV resistance included rtA181T (all clones) and rtN236T (four clones). The rtA181T mutation caused the W172* nonsense mutation in the overlapping S gene. In addition, all the clones harbored another nonsense mutation in the S gene (C69*) and a 207nt in-frame deletion in the preS1 region. These clones were converted to a 1.1mer construct for transient transfection of Huh7 cells. All the clones were deficient in hepatitis B surface antigen production. Three clones had similar levels of DNA replication. Comparison with a wild-type clone of the same genotype revealed a higher intracellular level of replicative DNA for clone c4, which was reduced by putting back the deleted 207nt, but not by co-transfection with an expression construct for the three surface proteins to rescue virion production. The HBcAg expression of the c4 and c4+207nt clones was mainly in the nucleus. Co-transfection with the L/M/S proteins expression construct did not alter the distribution of core. Clone c4 showed a significantly decreased susceptibility to ADV, a mild reduction in susceptibility to lamivudine and tenofovir, but remained sensitive to entecavir. In conclusion, this is an unusual ADV-resistant HBV isolate harboring two nonsense mutations in the S gene and a large in-frame deletion in the preS1 region, but still retains a high replication phenotype, which can provide a platform for recombinant vector construction.

N-Linked Glycosylation Is Not Essential for Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro.

Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles. However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles. Here, we investigated whether NTCP could explain the different behaviors of the two cell types. Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence. HepaRG cells stably transfected with an epitope-tagged NTCP expression construct displayed higher sHBV but not cHBV susceptibility than cells transfected with the null mutant. Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation. Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells. In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection. The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor. However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV. We found differentiated HepaRG cells expressed nonglycosylated NTCP despite a wild-type coding sequence. NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV. Overexpressing NTCP in HepRG cells did not increase infection by cell culture-derived HBV or distort the ratio between the two viral antigens. These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.

Validation and comparison of seventeen noninvasive models for evaluating liver fibrosis in Chinese hepatitis B patients.

BACKGROUND & AIMS: To avoid liver biopsy, many noninvasive models comprised of serum markers for liver fibrosis assessment have been developed. Given that most of them were developed in hepatitis C cohorts and few of them have been validated in Chinese hepatitis B patients, we aim to conduct this validation and compare their diagnostic accuracies in such a population. METHODS: A total of 937 HBV-infected patients who underwent liver biopsy were included in this single-centre retrospective study. The diagnostic accuracies of the 17 noninvasive models were assessed by areas under the receiver-operating characteristic curves (AUROCs), using histologically evaluated fibrotic stages of the biopsy specimens as standards. To compare efficiencies of the models, a grading system based on AUROC levels was developed. RESULTS: For discriminating significant fibrosis in all patients, the best three noninvasive models were King's score (AUROC = 0.756), Virahep-C model (AUROC = 0.756) and GPR (AUROC = 0.744); and for diagnosing cirrhosis, Lok index (AUROC = 0.832), FI (AUROC = 0.820) and FIB-4 (AUROC = 0.818) got the first three places. AUROCs in HBeAg-positive group were generally higher than those in HBeAg-negative group. In addition, based on the grading system, Virahep-C and GPR outstood others in evaluating liver fibrosis in all patients. CONCLUSIONS: In Chinese HBV-infected patients, Virahep-C models and GPR had high accuracies in diagnosing liver fibrosis and cirrhosis, while the most discussed models like APRI and FIB-4 did not outstand. Assessment should take into account the HBeAg sero-status, since these noninvasive models were more appropriate for HBeAg-positive patients than HBeAg-negative ones.

Role of quantitative hepatitis B core antibody levels in predicting significant liver inflammation in chronic hepatitis B patients with normal or near-normal alanine aminotransferase levels.

AIM: Chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels are not free from significant hepatic lesions. Recently, there has been an improved understanding of the clinical significance of quantitative hepatitis B core antibody levels (qAnti-HBc) during CHB management. In this cross-sectional study, we evaluated the utility of qAnti-HBc in identifying significant liver inflammation in CHB patients. METHODS: A total of 469 patients (training set, n = 363; validation set, n = 106) who underwent liver biopsy (LB) were included. The qAnti-HBc levels were quantified and the relationship between histology and serum markers was systematically analyzed. RESULTS: In the training set, qAnti-HBc levels were found to have significant diagnostic value for moderate to severe liver inflammation (≥G2) in all patients (area under the receiver operating characteristic curve [AUROC] = 0.768; 95% confidence interval [CI], 0.721-0.810; P < 0.001) and in patients with normal or near-normal ALT levels (AUROC = 0.767; 95% CI, 0.697-0.828; P < 0.001). Our novel index (AC index) for the identification of ≥G2 inflammation, which combined the qAnti-HBc and ALT levels, significantly improved diagnostic performance (AUROC = 0.813; 95% CI, 0.768-0.852) compared to the use of ALT alone (AUROC = 0.779; 95% CI, 0.732-0.821) in all patients. In the validation set, the AC index showed an improved AUROC of 0.890 (95% CI, 0.814-0.942) and 0.867 (95% CI, 0.749-0.943) in all patients and patients with normal ALT levels, respectively. CONCLUSIONS: The qAnti-HBc level predicts significant liver inflammation well, even in patients with normal or near-normal ALT levels. Compared with the conventional ALT level, the AC index is a more reliable non-invasive biomarker for significant liver inflammation in CHB patients.

Functional characterization of hepatitis B virus core promoter mutants revealed transcriptional interference among co-terminal viral mRNAs.

Hepatitis B virus (HBV) has a 3.2 kb circular DNA genome. It employs four promoters in conjunction with a single polyadenylation signal to generate 3.5, 2.4, 2.1 and 0.7 kb co-terminal RNAs. The 3.5 kb RNA is subdivided into the precore RNA for e-antigen expression and pregenomic RNA for genome replication. When introduced to a genotype A clone, several core promoter mutations markedly enhanced HBV genome replication, but suppressed e-antigen expression through up-regulation of pregenomic RNA at the expense of precore RNA. In this study, we found such mutations also diminished envelope proteins and hepatitis B surface antigen, products of the 2.1 and 2.4 kb subgenomic RNAs. Indeed, Northern blot analysis revealed overall increase in 3.5 kb RNA, but reduction in all subgenomic RNAs. To validate transcriptional interference, we subcloned 1.1×, 0.7× and 0.6× HBV genome, respectively, to a vector with or without a cytomegalovirus (CMV) promoter at the 5' end, so as to produce the pregenomic RNA, 2.4 kb RNA, and 2.1 kb RNA in large excess or not at all. Parallel transfection of the three pairs of constructs into a human hepatoma cell line confirmed the ability of pregenomic RNA to suppress all subgenomic transcripts and established the ability of the 2.4 and 2.1 kb RNAs to suppress the 0.7 kb RNA. Consistent with our findings, pregenomic RNA of the related duck HBV has been reported to interfere with transcription of the subgenomic RNAs. Transcriptional interference might explain why HBV produces so little 0.7 kb RNA and HBx protein despite a strong X promoter.

Partial virological response to entecavir treatment in nucleos(t)ide-naïve patients with HBeAg-positive chronic hepatitis B is not caused by reduced sensitivity.

Some patients with chronic hepatitis B (CHB) receiving entecavir (ETV) exhibit partial virological response (PVR) to ETV and the mechanism is not clear. In this study, we aim to investigate the in vitro susceptibility of residual clinical strains isolated from the sera of nucleos(t)ide-naïve hepatitis B virus e antigen (HBeAg)-positive patients with CHB and PVR to ETV, and to evaluate the clinical and virological responses to prolonged ETV monotherapy in these patients. We followed 69 nucleos(t)ide-naïve HBeAg-positive CHB patients receiving ETV treatment, with 13 partial responders to ETV. And we found that no genotypic resistance mutants were detected among the 13 PVR patients. Phenotypic analysis revealed that the residual HBV strains had normal replication capacity, and were as susceptible to ETV as wild-type HBV. All PVR patients continued to receive ETV monotherapy, and serum HBV DNA of the majority became undetectable after prolonged treatment. However, none of these patients achieved HBeAg loss. In contrast, 25.6% and 23.2% of the patients with virological response achieved HBeAg loss (P < 0.001) and HBeAg seroconversion (P < 0.001) at week 144, respectively. Thus, we conclude suboptimal response to ETV might not be due to reduced HBV susceptibility to ETV, and prolonging ETV monotherapy in patients with PVR is recommended.

Hepatitis B virus genotype C isolates with wild-type core promoter sequence replicate less efficiently than genotype B isolates but possess higher virion secretion capacity.

Infection by hepatitis B virus (HBV) genotype C is associated with a prolonged viremic phase, delayed hepatitis B e antigen (HBeAg) seroconversion, and an increased incidence of liver cirrhosis and hepatocellular carcinoma compared with genotype B infection. Genotype C is also associated with the more frequent emergence of core promoter mutations, which increase genome replication and are independently associated with poor clinical outcomes. We amplified full-length HBV genomes from serum samples from Chinese and U. S. patients with chronic HBV infection and transfected circularized genome pools or dimeric constructs of individual clones into Huh7 cells. The two genotypes could be differentiated by Western blot analysis due to the reactivities of M and L proteins toward a monoclonal pre-S2 antibody and slightly different S-protein mobilities. Great variability in replication capacity was observed for both genotypes. The A1762T/G1764A core promoter mutations were prevalent in genotype C isolates and correlated with increased replication capacity, while the A1752G/T mutation frequently found in genotype B isolates correlated with a low replication capacity. Importantly, most genotype C isolates with wild-type core promoter sequence replicated less efficiently than the corresponding genotype B isolates due to less efficient transcription of the 3.5-kb RNA. However, genotype C isolates often displayed more efficient virion secretion. We propose that the low intracellular levels of viral DNA and core protein of wild-type genotype C delay immune clearance and trigger the subsequent emergence of A1762T/G1764A core promoter mutations to upregulate replication; efficient virion secretion compensates for the low replication capacity to ensure the establishment of persistent infection by genotype C.

Conjugation of sulfonated aluminum phthalocyanine to doxorubicin can improve the efficacy of photodynamic cancer therapy.

Sulfonated aluminum phthalocyanine (AlPcS), a widely used photosensitizer for photodynamic therapy of cancer, was conjugated to doxorubicin (Dox), a chemotherapy drug, through electrostatic binding. The fluorescence resonance energy transfer from Dox to AlPcS showed the formation of AlPcS-Dox conjugates, as the fluorescence intensity of conjugated Dox was decreased and that of the AlPcS moiety was enhanced. This AlPcS-Dox conjugation was further confirmed by electrophoresis. The AlPcS-Dox conjugates enhanced the cellular uptake of AlPcS three times more than unconjugated AlPcS in both human hepatocellular carcinoma cell line 7701 and rat basophilic leukemia cell line. Moreover, the photodynamic killing effect of the conjugates was markedly increased as compared with that of AlPcS alone or the cytotoxicity of Dox alone, showing an enhanced effect of the AlPcS-Dox conjugates. These results indicate that the conjugation of a photosensitizer with a chemotherapy drug may improve photodynamic cancer therapy.

Enhancing intracellular NADPH bioavailability through improving pentose phosphate pathway flux and its application in biocatalysis asymmetric reduction reaction.

The intracellular NAD(P)H insufficiency is the key factor which limits the reduced product (such as chiral alcohols) synthesis by whole cell biocatalysis or microbial cell factory. In this paper, we reported a novel solution to increase NADPH supply through strengthening the pentose phosphate pathway (PPP) flux with overexpression of extra zwf (gene for glucose 6-phosphatedehydrogenase) and glk (gene for glucokinase) by recombinant Escherichia coli BL21(DE3)/pETDuet-1-glk-zwf and pET28a-bccr containing a carbonyl reductase gene bccr. The amount of intracellular NADPH was significantly increased from 150.3 µmol/L to 681.8 µmol/L after strengthening the PPP flux, which was 4.5-fold to that of the control. It was applied to improve the asymmetric reduction of 4-chloroacetoacetate to ethyl S-4-chloro-3-hydroxybutylate catalyzed by the BcCR, which increased the reaction yield 2.8-fold to the control. This strategy provides a new way to increase NADPH supply in E. coli cell factories.

Improved method for rapid and efficient determination of genome replication and protein expression of clinical hepatitis B virus isolates.

Different hepatitis B virus (HBV) genotypes and variants are associated with different clinical outcomes and/or response to antiviral therapy, yet the comparison of the in vitro replication capacity of a large number of clinical isolates remains technically challenging and time-consuming. Although the full-length HBV genome can be amplified from high-titer blood samples by PCR using High Fidelity(plus) DNA polymerase and primers targeting the conserved precore region, the HBV clones thus generated are replication deficient due to the inability to generate the terminally redundant pregenomic RNA essential for genome replication. The transfection experiment is further complicated by PCR errors and the presence of viral quasispecies. A previous study found that the precise removal of non-HBV sequence by SapI digestion led to HBV replication in transfected cells, possibly due to low-level genome circularization by a cellular enzyme. We released HBV genome from the cloning vector using BspQI, an inexpensive isoschizomer of SapI, and increased the efficiency of genome replication by an extra step of in vitro DNA ligation. The uncut plasmid DNA can be used for transfection if the sole purpose is to study envelope protein expression. We found significant PCR errors associated with the High Fidelity(plus) DNA polymerase, which could be greatly diminished using Phusion DNA polymerase or masked by the use of a clone pool. The reduced PCR error and modified enzymatic steps prior to transfection should facilitate a more widespread functional characterization of clinical HBV isolates, while the clone pool approach is useful for samples with significant sequence heterogeneity.

Impairment of hepatitis B virus virion secretion by single-amino-acid substitutions in the small envelope protein and rescue by a novel glycosylation site.

Mutations in the S region of the hepatitis B virus (HBV) envelope gene are associated with immune escape, occult infection, and resistance to therapy. We previously identified naturally occurring mutations in the S gene that alter HBV virion secretion. Here we used transcomplementation assay to confirm that the I110M, G119E, and R169P mutations in the S domain of viral envelope proteins impair virion secretion and that an M133T mutation rescues virion secretion of the I110M and G119E mutants. The G119E mutation impaired detection of secreted hepatitis B surface antigen (HBsAg), suggesting immune escape. The R169P mutant protein is defective in HBsAg secretion as well and has a dominant negative effect when it is coexpressed with wild-type envelope proteins. Although the S domain is present in all three envelope proteins, the I110M, G119E, and R169P mutations impair virion secretion through the small envelope protein. Conversely, coexpression of just the small envelope protein of the M133T mutant could rescue virion secretion. The M133T mutation could also overcome the secretion defect caused by the G145R immune-escape mutation or mutation at N146, the site of N-linked glycosylation. In fact, the M133T mutation creates a novel N-linked glycosylation site ((131)NST(133)). Destroying this site by N131Q/T mutation or preventing glycosylation by tunicamycin treatment of transfected cells abrogated the effect of the M133T mutation. Our findings demonstrate that N-linked glycosylation of HBV envelope proteins is critical for virion secretion and that the secretion defect caused by mutations in the S protein can be rescued by an extra glycosylation site.

Corrigendum to "miR-486 Promotes the Invasion and Cell Cycle Progression of Ovarian Cancer Cells by Targeting CADM1".

[This corrects the article DOI: 10.1155/2021/7407086.].

Novel Three-Dimensional Graphene-Like Networks Loaded with Fe3O4 Nanoparticles for Efficient Microwave Absorption.

A novel three-dimensional graphene-like networks material (3D-GLN) exhibiting the hierarchical porous structure was fabricated with a large-scale preparation method by employing an ion exchange resin as a carbon precursor. 3D-GLN was first studied as the effective microwave absorbing material. As indicated from the results of the electromagnetic parameter tests, and the minimum reflection loss (RL) of the 3D-GLN reached -34.75 dB at the frequency of 11.7 GHz. To enhance the absorption performance of the nonmagnetic 3D-GLN, the magnetic Fe3O4 nanoparticles were loaded on the surface of the 3D-GLN by using the hydrothermal method to develop the 3D-GLN/Fe3O4 hybrid. The hybrid exhibited the prominent absorbing properties. Under the matching thickness of 3.0 mm, the minimum RL value of hybrid reached -46.8 dB at 11.8 GHz. In addition, under the thickness range of 2.0-5.5 mm, the effective absorption bandwidth (RL < 10 dB) was 13.0 GHz, which covered part of the C-band and the entire X-band, as well as the entire Ku-band. The significant microwave absorption could be attributed to the special 3D network structure exhibited by the hybrid and the synergistic effect exerted by the graphene and the Fe3O4 nanoparticles. As revealed from the results, the 3D-GLN/Fe3O4 hybrid could be a novel microwave absorber with promising applications.

Elongated axial length and myopia-related fundus changes associated with the Arg130Cys mutation in the LIM2 gene in four Chinese families with congenital cataracts.

BACKGROUND: Congenital cataract (CC) is a congenital abnormality characterized by lens opacity present at birth and is associated with highly heterogeneous clinical manifestations. Lens-specific integral membrane protein (LIM2) gene expression is localized to tight junctional domains of different lens fiber membranes. To date, only four mutations in LIM2 have been reported to be associated with congenital or presenile cataracts. Due to the rarity of variants detected in the gene, there is limited progress in understanding the correlation between the genotype and phenotype of patients with mutations in LIM2. METHODS: A total of four Chinese families with CCs were recruited for this study, including three families inheriting in an autosomal dominant (AD) pattern and one sporadic case. Genomic DNA was extracted from the leukocytes of peripheral blood collected from all available patients. Whole-exome sequencing (WES) was performed on all probands and at least one of their parents. Bioinformatics analysis was performed to evaluate the pathogenicity of the candidate variants. Exon 4 of LIM2 was amplified by polymerase chain reaction and directly sequenced. All patients underwent full ocular examinations. This was an observational study to explore the genotype-phenotype relationships in the four families with a common candidate variant. RESULTS: Various ocular phenotypes were detected in these families, mainly including CCs, elongated axial length, and myopia-related fundus changes. The LIM2 gene mutation, p.Arg130Cys, was detected in all patients. This was further confirmed by Sanger sequencing. The proportion of probands with this mutation in our CCs database was 3.1% (4/130), which indicated that this mutation appears to be a frequent cause of cataracts in the Han Chinese population. This variation has been reported by other investigators before and was correlated with isolated cataracts. CONCLUSIONS: This is the first study that reports various ocular phenotypes associated with the p.Arg130Cys mutation in the LIM2 gene, which indicated the phenotypic heterogeneity of this gene. LIM2 might not only function as an integral membrane protein in lens fiber cells but also be associated with the axial development of the eyeball. Functional studies of the LIM2 gene are important and should receive more attention.

miR-486 Promotes the Invasion and Cell Cycle Progression of Ovarian Cancer Cells by Targeting CADM1.

OBJECTIVE: To explore the role and possible underlying mechanism of miR-486 in ovarian cancer (OC) cells. METHODS: The expression of miR-486 and CADM1 was detected by qRT-PCR in OC tissues and adjacent nontumor tissues and OC cell lines. The dual-luciferase reporter gene system was used to determine the targeting relationship between miR-486 and CADM1. CCK-8, colony formation assay, Transwell, and flow cytometry were performed to detect cell proliferation, cell invasion, cell cycle progression, and the apoptotic cell death, respectively. Western blot was carried out to detect the expression of CADM1 protein and the proteins associated with cell cycle progression. RESULTS: miR-486 was significantly upregulated in OC tissues and cells, while CADM1 expression was significantly downregulated. Dual-luciferase reporter assays further confirmed that CADM1 was a target gene of miR-486. Interference with miR-486 could inhibit the proliferation and invasion and promoted the apoptosis of SKOV3 cells. Knocking down both miR-486 and CADM1 significantly increased the SKOV3 cell proliferation, invasion, and the number of cells transitioning from the G0/G1 phase into the S phase of cell cycle and reduced the cellular apoptosis. Western blot analysis revealed that the expression of cell cycle progression-related proteins (CyclinD1, CyclinE, and CDK6) was significantly reduced, and the p21 expression was increased when interfering with both miR-486 and CADM1 expression. CONCLUSION: Our results suggested that miR-486 could act as a tumor promoter by targeting CADM1 and be a potential therapeutic target for the treatment of OC.