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Cryptococcosis is frequently found in immunosuppressed patients. It is also a significant opportunistic infection in non-immunocompromised individuals. In this study, we present a rare case of membranous nephropathy (MN) with pulmonary cryptococcosis. A 33-year-old man with MN was referred to our hospital because of dyspnea and weakness for 1 week. Before the above symptoms occurred, the dose of Cyclosporin A was increased again for relapse of MN. Multiple massive or patchy high-density shadows were present on computed tomography of the lung. Initially the patient underwent empirical anti-bacterial therapy, which turned out to be ineffective. As the results of serum cryptococcal latex agglutination tests were positive, the administration of anti-fungal drugs was prescribed. The results of fungal culture and pathologic examination of the lung tissue revealed the findings consistent with Cryptococcus neoformans. The patient was successfully treated with voriconazole followed by fluconazole with satisfactory result. Therefore, in patients with chronic kidney disease, lung lesions with poor bactericidal effects of cephalosporins need further examination to make sure whether there is pulmonary cryptococcosis. Early diagnosis and treatment might contribute to good results. It is a problem worthy of consideration that whether immunosuppressive agents need to be discontinued or not during antifungal therapy.

In order to explore the interaction between meloxicam and trypsin, the interaction mechanism between meloxicam and trypsin was studied by fluorescence spectrum, UV-vis absorption spectrum, ...

The mechanism of interaction between cefonicid sodium and pepsin was investigated by various spectroscopic methods and molecular docking. Cefoncid sodium quenched the intrinsic fluorescence...

Under the experimental condition of pH=7.40, papain (PAPA) was used as the detection object, and the binding behavior of cefoperazone sodium (CFZ) and PAPA at three temperatures was studied by mult...

Background Breast cancer is the most common cancer in women worldwide, high-resolution dynamic contrast-enhanced MRI (DCE-MRI) can better evaluate the tissue microenvironment and texture characteristics. The purpose of this study was to investigate the value of the texture-based analysis for breast DCE-MRI in the diagnosis of breast lesions and background enhancement. Methods This study prospectively enrolled 128 patients with clinically suspected breast lesions in our hospital from April 2015 to June 2017. Among them, 62 patients underwent preoperative high temporal resolution DCE-MRI (1 + 26 phases) scan with 39 malignant and 23 benign lesions. The control group retrospectively and randomly contained 78 patients who underwent preoperative low temporal resolution DCE-MRI (1 + 5 phases) scans with 46 malignant and 32 benign lesions. Quantitative parameters were obtained using a two-compartment Extended Tofts and volume of interest model for the lesion center, surrounding peripheral area and background enhancement, including pharmacokinetic parameters (Ktrans, Kep, Ve and Vp) and texture features based on the Ktrans map. The Student’s t-test was used to compare the differences of means. LASSO was used for dimension reduction and logistic regression analysis was used for model construction. A receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance. Results Pharmacokinetic parameters were significantly different between high temporal resolution and low temporal resolution DCE-MRI (P trans of the lesion area on high temporal resolution DCE-MRI was significantly correlated to the pathological grading (r = 0.400, P = 0.012). In the differentiation between benign and malignant lesions, the ROC analysis demonstrated that the diagnostic value of high temporal resolution DCE-MRI offered slightly significant advantages in the realms of the lesion, peripheral areas and background enhancement. Conclusions The use of texture analysis based on high temporal resolution DCE-MRI may potentially improve breast cancer diagnostic performance. Specifically, combining the lesion, peripheral, BE area, and Ktrans-mean parameters can contribute to the diagnosis of breast lesions, background enhancement and the pathological grading of malignant tumors.

The interaction of pioglitazone hydrochloride bound to tryptophan residues and tyrosine residues in bovine transferrin was investigated using synchronous fluorescence spectroscopy at various temper...

The interaction mechanism between nifedipine (NDP) and pepsin (PEP) at 298, 310, and 318 K was studied by various spectroscopic techniques and molecular docking. The experimental results showed that NDP mainly quenched the fluorescence of PEP by dynamic quenching of non-radiative energy transfer, but no significant changes in the secondary structure of PEP. The protein binding rate (W) of NDP measured at 310 K was 71.79–89.15%, and a binding rate model of NDP and PEP was established, W = − 0.1273R2 − 0.0519R + 0.8973. Hill’s coefficients were approximately 1, which showed that the interaction of NDP and PEP will not affect the binding of subsequent drug to the protein. The molecular docking technique was used to simulate the interaction between NDP and PEP, the results demonstrated that the binding site of NDP is located in the active center of pepsin, which was consistent with the conclusion of the spectroscopic method, and it was also proved that the interaction of PEP–NDP system was driven by hydrophobic and hydrogen bonding.

The extent to which drugs combine with trypsin is influenced by the interaction of tartrazine and trypsin, which may cause overdose or underdose of drugs. Therefore, the interaction of tartrazine and trypsin is investigated by methods of spectrometry in this paper. The binding rate of tartrazine to trypsin is 80.95–95.71% at 310 K, and Hill’s coefficients are almost 1. The effect of tartrazine on trypsin structure was studied by synchronous and circular dichroism. The results showed that the binding of tartrazine and trypsin induced the conformational change of trypsin, and quenched the endogenous fluorescence in trypsin. The results of molecular docking revealed that tartrazine is located in the catalytic active site of trypsin, and is consistent with that of experimental calculation.

This study aims to investigate the interaction between glipizide and bovine hemoglobin using fluorescence quenching, circular dichroism spectroscopy in various temperatures (293, 303, and 3...

Mercury (Hg) is a ubiquitous environmental toxicant with important public health implications. Hg causes neurotoxicity through astrocytes, Ca2+, neurotransmitters, mitochondrial damage, elevations of reactive oxygen species and post-translational modifications. However, the similarities and differences between the neurotoxic mechanisms caused by different chemical forms of Hg remain unclear. Zebrafish embryos were exposed to methylmercury (MeHgCl) or mercury chloride (HgCl2) (0, 4, 40, 400 nM) up for 96 h. HgCl2 exposure could significantly decrease survival rate, body length and eye size, delay the hatching period, induce tail bending and reduce the locomotor activity, and these effects were aggravated in the MeHgCl group. The compounds could increase the number of apoptotic cells in the brain and downregulate the expression of Shha, Ngn1 and Nrd, which contribute to early nervous development. The underlying mechanisms were investigated by metabolomics data. Galactose metabolism, tyrosine metabolism and starch and sucrose metabolism pathways were disturbed after HgCl2 or MeHgCl exposure. In addition, the levels of three neurotransmitters including tyrosine, dopamine and tryptophan were reduced after HgCl2 or MeHgCl exposure. Oxidative stress is related to metabolite changes, such as changes in the putrescine, niacinamide and uric acid contents in the HgCl2 group, and squalene in the MeHgCl group. These data indicated that downregulation of these genes and abnormal metabolic profile and pathways contribute to the neurotoxicity of HgCl2 and MeHgCl.

Background Mutations of PKD1 and PKD2 accounted for the most cases of autosomal dominant polycystic kidney disease (ADPKD). The presence of the large transcript, numerous exons and complex reiterated regions within the gene has significantly complicated the analysis of PKD1 with routine PCR-based approaches. Methods We developed a strategy to analyze both the PKD1/PKD2 genes simultaneously using targeted next-generation sequencing (NGS). All coding exons plus the flanking sequences of PKD1 and PKD2 genes from probands were captured, individually barcoded and followed by HiSeq2000 sequencing. The candidate variants were validated by using classic Sanger sequencing. PKD1-specific primers were designed to amplify the replicated areas of PKD1 gene. Results Five novel variations and one known mutation in PKD1 gene were detected in five familial and one sporadic Chinese ADPKD patients. Through pedigree and bioinformatic analysis, five of them were identified as pathogenic mutations (p.G1319R, p.Y3781*, p.W4122*, p.Val700Glyfs*14, and p.Leu3656Trpfs*28) and one was as polymorphism (p.T2420I). Conclusions Our result showed that targeted capture and NGS technology were effective for the gene testing of ADPKD disorder. Mutation study of PKD1 and PKD2 genes in Chinese patients may contribute to better understanding of the genetic diversity between different ethnic groups and enrich the mutation database in Asian population.

This study aims to investigate the interaction between cefonicid sodium (CFS) and papain (PAPA) using fluorescence spectroscopy, synchronous fluorescence spectroscopy and molecular docking methods. The results indicated that the fluorescence intensity of PAPA was decreased considerably upon the addition of CFS through a static quenching mechanism. Synchronous fluorescence spectroscopy studies showed that the combination of CFS and PAPA could change the conformation of PAPA. At the temperature of 293 K, there was a good linear relationship between the fluorescence intensity of the system and the concentration of CFS in the range of 6.0×10-6 to 1.0×10-4 mol/L and the detection limit of the method was 3.05×10-6 mol/L (n=10). From the results of the thermodynamic constant and molecular model analysis, it could be inferred that the CFS and PAPA molecules mainly combine by electrostatic attraction and hydrogen bonding. The binding model was established based on the experimental data, and the binding rate data of CFS and PAPA was obtained. The results showed that taking PAPA while taking CFS was safe.

The reaction mechanism of cefepime (CEF) with papain (PAPA) was investigated by both fluorescence quenching and synchronous fluorescence spectroscopy in different temperature (293, 308 and 318 K). The results demonstrated that the interaction between CEF and PAPA was taking place via static quenching. Thermodynamic parameters revealed that electrostatic interaction played major roles in the interaction. The order of magnitudes of binding constant is 104, and the number of binding site in the system was closed to 1. The binding rates of CEF to PAPA (λex = 280 nm) were 81.46%~95.95% (293K), 80.50%~95.49% (308K) and 79.77%~95.12% (318K). There was a linear relationship between ΔF and the concentrations of CEF in the range of 6.0×10-6~7.0×10-5 mol/L. And the correlation coefficient of the linear curve was 0.9973.

In this paper, the fluorescence spectra of Enrofloxacin (ENR) in different pH conditions was studied in order to determine its structural changes due to protonation with pH changes. The ENR two-step dissociation constant is calculated and the fluorescence quantum yield under acidic conditions is measured. In the strong acidic conditions, ENR exists of H3L 2+ form of which maximum emission wavelength is at 450 nm. At the condition of pH 2.45 to 4.23, ENR exists of H 2 L + form with strong and steady fluorescence. The maximum emission wavelength is still 450 nm. At the condition of pH more than 4.23, the maximum emission wavelengths are gradually blue shifted to 445 nm and the fluorescence intensity decrease with the increase of pH which shows that H 2 L + loses one proton with the increase of pH and exists in the form of bipolar ion HL. When the pH is more than 12.28, the fluorescence intensity are weakened to nearly disappear with the increase of pH value, indicating that HL gradually loses the proton with the conversion to the anion of L - which is weaker fluorescence. In the buffer solution of pH 3.00, with quinine sulfate as reference, the fluorescence quantum yield of ENR at excitation wavelength of 274 nm is 0.125.

The reaction mechanism of rhodamine B (RHB) with bovine serum albumin (BSA) was investigated using fluorescence spectroscopy and synchronous fluorescence spectroscopy at different temperatures (298 K, 310 K and 318 K). The results showed that electrostatic force played a major role on the conjugation reaction between BSA and RHB, and the type of quenching was static quenching. Primary binding site for RHB was sub-hydrophobic domain IIA, and the number of binding sites was 1. The order of magnitude of binding constants ( K a ) was 10 4 . The value of Hill’s coefficients ( n H ) was approximately equal to 1, which suggested no cooperativity in BSA-RHB system. The donor-to-acceptor distance r < 7 nm indicated that the static fluorescence quenching of BSA by RHB was also a non-radiation energy transfer process. The results of two methods were consistent that showed the synchronous fluorescence spectroscopy could be used to study the reaction mechanism between drug and protein, and was a useful supplement to the conventional fluorescence quenching method.

To identify the genetic etiology in a Chinese patient with neurofibromatosis type 1 (NF-1).All coding exons and the flanking sequences of neurofibromin 1 (NF1) gene from the patient were captured, individually barcoded and subjected to HiSeq2000 high-throughput sequencing. Suspected mutation was validated in the nuclear family members with Sanger sequencing.A novel indel mutation, c.789_790delAGinsT, was identified in the exon 8 of the NF1 gene in the patient but not in her asymptomatic parents. The mutation was predicted to have caused shifting of the reading frame and a premature downstream stop codon (p.K263Nfs*18). Two known polymorphisms, c.888+108 CT (rs2953000) and c.888+118 GT (rs2952999), was detected in the flanking of the indel mutation in the patient and her father. Sequencing chromatogram for the family indicates that above changes are located on the same chromosome.The c.789_790delAGinsT, as a de novo mutation occurring on the paternally derived chromosome, is most likely to be causative for the disease. Compared with Sanger sequencing, targeted next-generation sequencing is more efficient and can dramatically reduce the cost for the genetic testing of NF-1.