Analysis of PROS1 mutations and clinical characteristics in three Chinese families with hereditary protein S deficiency.

We report three heterozygous PROS1 mutations that caused type I protein S deficiency in three unrelated Chinese families. We measured protein S activity and antigen levels for all participants, screened them for mutations in the PROS1 gene. And we employed the calibrated automated thrombin generation (CAT) method to investigate thrombin generation. Numerous bioinformatics tools were utilized to analyze the conservation, pathogenicity of mutation, and spatial structure of the protein S. Phenotyping analysis indicated that all three probands exhibited simultaneous reduced levels of PS:A, TPS:Ag, and FPS:Ag. Genetic testing revealed that proband A harbored a heterozygous c.458_458delA (p.Lys153Serfs*6) mutation in exon 5, proband B carried a heterozygous c.1687C>T (p.Gln563stop) mutation in exon 14, and proband C exhibited a heterozygous c.200A>C (p.Glu67Ala) mutation in exon 2. Bioinformatic analysis predicted that the p.Lys153Serfs*6 frameshift mutation and the p.Gln563stop nonsense mutation in the protein S were classified as "disease-causing." The identification of the novel mutation p.Lys153Serfs*6 in PROS1 enriches the Human Genome Database. Our research suggests that these three mutations (p.Lys153Serfs*6, p.Gln563stop, and p.Glu67Ala) are possibly responsible for the decreased level of protein S in the three families. Furthermore, the evidence also supports the notion that individuals who are asymptomatic but have a family history of PSD can benefit from genetic analysis of the PROS1 gene.

Effects of Graphene Oxide on Endophytic Bacteria Population Characteristics in Plants from Soils Contaminated by Polycyclic Aromatic Hydrocarbons.

Environmental pollution stands as one of the significant global challenges we face today. Polycyclic aromatic hydrocarbons (PAHs), a class of stubborn organic pollutants, have long been a focal point of bioremediation research. This study aims to explore the impact and mechanisms of graphene oxide (GO) on the phytoremediation effectiveness of PAHs. The results underscore the significant efficacy of GO in accelerating the degradation of PAHs. Additionally, the introduction of GO altered the diversity and community structure of endophytic bacteria within the roots, particularly those genera with potential for PAH degradation. Through LEfSe analysis and correlation studies, we identified specific symbiotic bacteria, such as Mycobacterium, Microbacterium, Flavobacterium, Sphingomonas, Devosia, Bacillus, and Streptomyces, which coexist and interact under the influence of GO, synergistically degrading PAHs. These bacteria may serve as key biological markers in the PAH degradation process. These findings provide new theoretical and practical foundations for the application of nanomaterials in plant-based remediation of polluted soils and showcase the immense potential of plant-microbe interactions in environmental restoration.

Nitrogen removal performance of aerobic denitrifying bacteria enhanced by an iron-anode pulsed electric field.

Pulsed electric field (PEF) technology has attracted considerable attention because it can efficiently treat pollutants that are difficult to degrade. In this study, a PEF system using iron as the electrode was constructed to investigate the effect of PEF-Fe on the growth and metabolism of aerobic denitrifying bacteria and the effectiveness of wastewater nitrogen removal. The chemical oxygen demand, NO3--N and nitrate removal rates were 98.93%, 97.60% and 24.40 mg·L-1·h-1, respectively, under optimal conditions. As confirmed in this study, PEF-Fe could improve the key enzyme activities of W207-14. Scanning electron microscopy revealed that the surface of PEF-Fe-treated W207-14 was intact and smooth without any irreversible deformation. Flow cytometry combined with fluorescence staining analysis also confirmed reversible electroporation on the cell membrane surface of PEF-Fe-treated W207-14. Differentially expressed gene enrichment analysis showed that PEF-Fe activated the transmembrane transport function of ATP-binding cassette transporte (ABC) transport proteins and enhanced the cell membrane permeability of aerobic denitrifying bacteria. The significant differential expression of iron-sulphur cluster proteins facilitated the regulation of electron transport and maintenance of the dynamic balance of iron ions within the PEF-Fe system.

[Analysis of hereditary coagulation factor â ª deficiency in a Chinese pedigree with compound heterozygous mutations].

OBJECTIVE: To explore the molecular mechanisms of a Chinese pedigree with hereditary factor Ⅺ (FⅪ) deficiency. METHODS: All of the 15 exons, flanking sequences of the FⅪ gene and the corresponding mutation sites of family members were analyzed by the Sanger sequencing, followed by the extraction of the peripheral blood genomic DNA. And all the results were verified by the reverse sequencing. The conservation of the mutated sites was analyzed by the ClustalX-2.1-win. Three online bioinformatics software tools, including Mutation Taster, PolyPhen2 and the PROVEAN, were used to assess the possible impact of the mutations. Swiss-pdbviewer software was used to analyze the effects of mutant amino acids on protein structure. RESULTS: Genetic analysis revealed that the proband had compound heterozygous mutations including a nonsense mutation of c.1107C>A (Tyr369stop) in exon 10 and missense mutation of c.1562A>G (Tyr521Cys) in exon 13. The same c.1107C>A (Tyr369stop) was present in her father, the same c.1562A>G (Tyr521Cys) was present in both her mother and daughter. Conservation analysis indicated that Tyr521 was a highly conserved site during evolution. The prediction of pathogenicity showed that both c.1107C>A and c.1562A>G were pathogenic mutations. Protein structure prediction showed that in the wild type FⅪ protein structure, Tyr521 formed a hydrogen bond with the Lys572 and Ile388, respectively. When Tyr521 was replaced by Cys521, the original benzene ring structure disappeared, and side chains of Lys572 added a hydrogen bond with the Cys521, which may change protein catalytic domain structure. When Tyr369 was mutated to a stop codon, resulting in the truncated protein. CONCLUSION: The compound heterozygous mutations including the c.1107C>A heterozygous missense variant in exon 10 and the c.1562A>G heterozygous nonsense mutation in exon 13 may be responsible for the hereditary factor Ⅺ deficiency in this Chinese pedigree.

Identification of dyslipidemia as a risk factor for sudden sensorineural hearing loss: A multicenter case-control study.

BACKGROUND: Recently, several studies have reported an association between lipid profiles and sudden sensorineural hearing loss (SSNHL), yet there is considerable variability between the individual studies in defining the precise association between serum lipids levels and SSNHL. This study sought to identify a possible relationship between dyslipidemia and the prevalence and prognosis of SSNHL. METHODS: A case-control study was carried out at two independent medical centers, including 2,288 SSNHL patients and 2,288 healthy controls. Clinical characteristics and serum lipid parameters were assessed, including total cholesterol (CHOL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (Trig), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), and lipoprotein a (Lpa). Multivariate logistic regression analysis was performed to assess the relationship between lipid profiles and SSNHL in the 4,576 subjects. RESULTS: Significant differences were identified in several conventional serum lipid markers including CHOL, Trig, HDL, LDL, ApoAI, ApoB, and Lpa, between SSNHL patients and healthy controls. Serum ApoAI levels were significantly lower in patients with bilateral SSNHL compared to unilateral SSNHL. Binary logistic regression analysis revealed that higher levels of ApoB, LDL, Trig, and lower levels of ApoAI and HDL were all associated with an increased risk of SSNHL. After clinical characterization, multivariate analysis showed that only low levels of ApoB predicted likelihood of a recovery of more than 30 dB among patients with SSNHL. CONCLUSIONS: Serum lipids are associated with the incidence and prognosis of SSNHL. Identification of dyslipidemia may improve early evaluation and management of SSNHL risks.

[Phenotypic and genotypic analysis of a pedigree affected with hereditary protein C deficiency due to heterozygous deletional mutation of PROC gene].

OBJECTIVE: To analyze the phenotype and genetic variants of a pedigree affected with hereditary protein C (PC) deficiency. METHODS: The protein C activity (PC:A) of the proband and her family members (a four-generation pedigree including 11 individuals) were tested by chromogenic substrate method, and the protein C antigen (PC:Ag) was detected with an enzyme-linked immunosorbent assay(ELISA). The 9 exons and flanking sequences of the protein C (PROC) gene were amplified by PCR and directly sequenced. Suspected mutation was validated by clone sequencing and in other members of the family. MutationTaster and ClustalX-2.1-win was used to analyze the pathogenicity and conservation of the mutation site,respectively. Three-dimentional protein model and amino acids interaction were analyzed with Swiss-PdbViewer software. RESULTS: The PC: A and PC: Ag of the proband were decreased to 46% (reference range: 70%-130%) and 50% (referencerange:70%-140%), respectively. Her grandmother,aunt, cousin and younger brother also showed declined PC:A and PC:Ag by approximately 50%. Genetic analysis revealed that the above individuals have all carried a deletional mutation c.1212-1212delG (p.Met364TrpfsX15) in exon 9 of the PROC gene which can cause replacement of Methionine at position 364 by Tryptophan and alteration of 15 downstream amino acids, and produce a premature stop codon at position 378. The score of MutationTaster was 1.000, indicating that the variant is pathogenic. Conservative analysis showed that the 15 altered amino acids are located in a conserved region across nine homologous species. Protein model analysis showed that the mutation has disrupted a catalytic domain of protein C thereby affected its function. CONCLUSION: The heterozygous c.1212-1212delG deletional mutation in exon 9 of the PROC gene, which was unreported previously,probably accounts for the decrease of PC:A and PC:Ag in this pedigree.

Determination of Alzheimer biomarker DNA by using an electrode modified with in-situ precipitated molybdophosphate catalyzed by alkaline phosphatase-encapsulated DNA hydrogel and target recycling amplification.

An electrochemical biosensor is described for highly sensitive determination of tDNA, an Alzheimer's disease (AD)-related biomarker. Electroactive molybdophosphate anions were precipitated in-situ on a glassy carbon electrode (GCE) via catalytic hydrolysis by alkaline phosphatase (ALP). This is followed by recycling amplification of tDNA. Four DNA strands (referred to as S1, S2, S3 and S4) were designed to assemble X-shape DNA (X-DNA) building blocks. These were further extended into four directions under the action of DNA polymerase. The resultant two X-DNA motifs were polymerize. Simultaneously, ALP is encapsulated into a hydrogels network to obtain a porous material of type ALP@DNAhg. The GCE was modified with reduced graphene oxide functionalized with gold nanoparticles (Au@rGO). If ALP@DNAhg are captured via strand displacement, tDNA recycling assembly for signal amplification is initiated. This results in the immobilization of large amounts of ALP. On introduction of pyrophosphate and molybdate (MoO42-), ALP will catalyze the hydrolysis of pyrophosphate to produce phosphate. It will react with molybdate to form redox active phosphomolybdate anions (PMo12O403-). Its amperometrical signal depends on the concentration of tDNA in the 1.0 × 10-2 to 1.0 × 104 pM concentration range, and the detection limit is 3.4 × 10-3 pM. Graphical abstract Schematic presentation of (a) preparation of alkaline phosphatase-encapsulated DNA hydrogel (ALP@DNAhg). (b) fabrication of the biosensor for target DNA (tDNA) based on ALP@DNAhg to catalyze in situ precipitation of electroactive molybdophosphate anion (PMo12O403-) and tDNA recycling amplification, achieving tDNA-dependent electrochemical signal readout (X-DNA: X-shape DNA building block. TdT: terminal deoxynucleotidyl transferase. dATP: deoxyadenosine triphosphate. dTTP: deoxythymidine triphosphate. X-DNA-pAn and X-DNA-pTn: X-DNA motifs with poly-A and poly-T tails. ALP: alkaline phosphatase. ALP@DNAhg: ALP-encapsulated DNA hydrogels. Au@rGO: gold nanoparticles-functionalized reduced graphene oxide. GCE: glass carbon electrode. HP1, 2: hairpin DNA 1, 2. MCH: 6-mercaptohexanol. tDNA: target DNA. CV: cyclic voltammetry).

[Identification of compound heterozygous mutations of F11 gene in a pedigree affected with heriditary coagulation factor XI deficiency].

OBJECTIVE: To identify potential mutations of F11 gene in a pedigree affected with hereditary coagulation factor XI (FXI) deficiency and explore its molecular pathogenesis. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), coagulation factor VIII activity (FVIIIC), coagulation factor IX activity (FIXC), coagulation factor XI activity (FXIC), coagulation factor XII activity (FXIIC) and lupus anticoagulation (LA) of the proband and eight family members were determined. FXI antigen (FXIAg) was determined by enzyme-linked immunosorbent assay (ELISA). For the proband, potential mutations in the exons, flanking introns and 5'-, 3'-untranslated regions of the F11 gene were screened by direct DNA sequencing. The results were confirmed by reverse sequencing. Suspected mutations were detected in other family members. ClustalX-2.1-win and four online bioinformatic tools (PolyPhen-2, PROVEAN, SIFT, and Mutation Taster) were used to study the conservation and possible impact of the mutations. The structure of the mutational sites was processed with Swiss-PdbViewer. RESULTS: The propositus had prolonged APTT (69.6 s), whose FXIC and FXIAg were reduced to 6.0% and 10.7%, respectively. Her mother, elder sister, one younger sister, little brother, daughter and son showed slightly prolonged APTT and moderate FXIC and FXIAg levels. Gene sequencing revealed that the propositus carried a heterozygous nonsense mutation c.738G>A (p.Trp228stop) in exon 7 and a heterozygous mutation c.1556G>C (p.Trp501Ser) in exon 13. Her mother, elder sister and daughter were heterozygous for the p.Trp228stop mutation, while one younger sister and little brother and son were heterozygous for p.Trp501Ser. Her husband and the youngest sister were of the wild type. Phylogenetic analysis suggested that Trp501 was highly conserved among all homologous species. The p.Trp501Ser was predicted to be "probably damaging","deleterious", "affect protein function" and "disease causing" corresponding to PolyPhen-2, PROVEAN, SIFT and Mutation Taster. Model analysis demonstrated that the non-polar Trp501 has two benzene rings, forming a hydrogen bond with Gln512 in the wild type. Once substituted by Ser501, the side chain may form another hydrogen bond with the benzene of His396. This may affect the normal space conformation and stability of FXI protein. CONCLUSION: The compound heterozygous mutations of the F11 gene probably accounted for the low FXI concentration in this pedigree.

Influence Factors on Contrast Agent Venous Intravasation During Transvaginal 4-Dimensional Hysterosalpingo-Contrast Sonography.

OBJECTIVES: To explore the risk factors on contrast agent venous intravasation during transvaginal 4-dimensional hysterosalpingo-contrast sonography (TVS 4D-HyCoSy). METHODS: The TVS 4D-HyCoSy imaging data were collected from 276 female infertile patients. The correlation between endometrial thickness, days after menstruation, intrauterine intervention history, fallopian tubal patency degree, and contrast agent venous intravasation, respectively, was analyzed. RESULTS: In our study, the incidence of contrast agent venous intravasation was 13.04%. Endometrial thickness and days after menstruation were significantly associated with venous intravasation (P < .05). However, there was no significance for intrauterine intervention history and fallopian tube patency degree. CONCLUSIONS: Contrast agent intravasation during TVS 4D-HyCoSy is not infrequent. Performing TVS 4D-HyCoSy according to endometrial thickness and menstrual period could reduce intravasation incidence to some extent.

A cascade amplification strategy of catalytic hairpin assembly and hybridization chain reaction for the sensitive fluorescent assay of the model protein carcinoembryonic antigen.

A cascade nucleic acid amplification strategy is presented for fluorometric aptamer based determination of the model protein carcinoembryonic antigen (CEA). Amplification is accomplished by combining catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR). In this assay, a specially designed single-stranded DNA containing the aptamer sequence (AS) specific for CEA is hybridized with an inhibitor strand (IS) to form a double-stranded DNA (IS@AS). In the presence of CEA, it will recognize and bind to the AS strand which causes the release of IS. By introducing two DNA hairpins (H1 and H2; these containing complementary sequences) CHA will be activated via the hybridization reactions of H1 and H2. This is accompanying by the formation of a double-stranded DNA (H1-H2) and the release of CEA@AS. The liberated CEA@AS further drives successive recycling of the CHA, thereby generating further copies of H1-H2. The resultant H1-H2 hybrids act as primers and trigger HCR with the help of other two DNA hairpins (H3 and H4) containing G-rich toehold at the 5'-terminus and 3'-terminus of H3 and H4, respectively. The fluorescent probe N-methyl mesoporphyrin IX (NMM) is finally intercalated into the G-rich domains of the long DNA nanostructures due to formation of G-quadruplex structures. This generates a fluorescent signal (best measured at excitation/emission wavelengths of 399/610 nm) that increases with the concentration of target (CEA). This aptamer-based fluorescence assay is highly sensitive and has a linear range that covers the 1 pg·mL-1 to 2 ng·mL-1 CEA concentration range, with a 0.3 pg·mL-1 detection limit. Graphical abstract By integrating catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) for effective signal enhancement, a novel cascade amplification strategy is presented to develop a sensitive and selective fluorescent method for the assay of the model protein carcinoembryonic antigen (CEA).

A sub-picomolar assay for protein by using cubic Cu2O nanocages loaded with Au nanoparticles as robust redox probes and efficient non-enzymatic electrocatalysts.

In this work, a simple and sensitive electrochemical aptasensor for protein (thrombin - TB used as the model) was developed by using cubic Cu2O nanocages (Cu2O-NCs) loaded with Au nanoparticles (AuNPs@Cu2O-NCs) as non-enzymatic electrocatalysts and robust redox probes. Through the specific sandwich-type reaction between TB and TB aptamers (TBA), the formed AuNPs@Cu2O-NCs bound with NH2-TBA were captured onto the electrode surface modified with SH-TBA. Based on the inherent redox activity of AuNPs@Cu2O-NCs with cubic nanostructures, a detectable electrochemical signal was generated which was dependent on the analyte concentration. Meanwhile, AuNPs@Cu2O-NCs showed an efficient electrocatalytic capability in the reduction of H2O2, resulting in a significant enhancement of the response signal. Thus, the simplification of the proposed strategy and the improvement of analytical performances were easily achieved with a sub-picomolar sensitivity (the limit of detection was 0.066 pmol L-1). The applicability of the simple and sensitive aptasensor was successfully demonstrated by assaying TB in human serum samples. This non-enzymatic detection platform would be potential and promising in clinical diagnostics and protein analysis techniques.

Real-time quantum feedback prepares and stabilizes photon number states.

Feedback loops are central to most classical control procedures. A controller compares the signal measured by a sensor (system output) with the target value or set-point. It then adjusts an actuator (system input) to stabilize the signal around the target value. Generalizing this scheme to stabilize a micro-system's quantum state relies on quantum feedback, which must overcome a fundamental difficulty: the sensor measurements cause a random back-action on the system. An optimal compromise uses weak measurements, providing partial information with minimal perturbation. The controller should include the effect of this perturbation in the computation of the actuator's operation, which brings the incrementally perturbed state closer to the target. Although some aspects of this scenario have been experimentally demonstrated for the control of quantum or classical micro-system variables, continuous feedback loop operations that permanently stabilize quantum systems around a target state have not yet been realized. Here we have implemented such a real-time stabilizing quantum feedback scheme following a method inspired by ref. 13. It prepares on demand photon number states (Fock states) of a microwave field in a superconducting cavity, and subsequently reverses the effects of decoherence-induced field quantum jumps. The sensor is a beam of atoms crossing the cavity, which repeatedly performs weak quantum non-demolition measurements of the photon number. The controller is implemented in a real-time computer commanding the actuator, which injects adjusted small classical fields into the cavity between measurements. The microwave field is a quantum oscillator usable as a quantum memory or as a quantum bus swapping information between atoms. Our experiment demonstrates that active control can generate non-classical states of this oscillator and combat their decoherence, and is a significant step towards the implementation of complex quantum information operations.

[Dynamic changes of reproductive hormone levels and related factors in old and middleaged men in health examination].

OBJECTIVE: To investigate the dynamic changes of serum reproductive hormone levels in old and middleaged males in health examination and their correlation with age and lipid profile. METHODS: This study included 4 333 men in health examination from January 2011 to December 2014. The men were aged from 40 to 85 years old and divided into seven fiveyearspan age groups. We determined the levels of serum testosterone (T), luteinizing hormone (LH), folliclestimulating hormone (FSH), estradiol (E2), progesterone (P), prolactin (PRL), total cholesterol (TC), triglyceride (TG), lowdensity lipoprotein cholesterol (LDLC), highdensity lipoprotein cholesterol (HDLC), and the testosterone secretion index (TSI = T/LH). We analyzed the obtained data using SPSS Pram, KruskalWallis H test, MannWhitney U test, exponential regression, and Spearman correlation analysis. RESULTS: Statistically significant differences were found in LH, FSH, E2 and TSI among the seven age groups (P< 0.05). The levels of serum LH, FSH and E2 were significantly higher (P< 0.05) while TSI remarkably lower (P< 0.05) in the ≥70 yr group than in the other six groups. The serum T and E2 levels and TSI were markedly lower in the 40－44, 45－49 and 50－54 yr groups in 2014 than in the other three years (P< 0.05), and so were the levels of serum T and TSI in the 55－59 yr group (P< 0.05). The levels of serum LH, FSH and E2 were correlated positively while those of P, PRL and TSI negatively with age. The serum T level was correlated positively with HDLC but negatively with TC, TG and LDLC. The levels of serum LH, FSH and E2 showed a yearly average increase of 1.9%, 2.7% and 0.5%, respectively, while TSI an annual mean decline of 2.0% in the 40－85 yr group. CONCLUSIONS: LH, FSH and E2 were increased while TSI decreased with age in the >40 years old males. T and TSI were reduced in the 40－59 years old men from 2011 to 2014, and so was E2 in the 40－54 yr group. Lowlevel testosterone is closely related to dyslipidemia.

Reduced Connexin26 in the Mature Cochlea Increases Susceptibility to Noise-Induced Hearing Lossin Mice.

Connexin26 (Cx26, encoded by GJB2) mutations are the most common cause of non-syndromic deafness. GJB2 is thought to be involved in noise-induced hearing loss (NIHL). However, the role of Cx26 in NIHL is still obscure. To explore the association between Cx26 and NIHL, we established a Cx26 knockdown (KD) mouse model by conditional knockdown of Cx26 at postnatal day 18 (P18), and then we observed the auditory threshold and morphologic changes in these mice with or without noise exposure. The Cx26 KD mice did not exhibit substantial hearing loss and hair cell degeneration, while the Cx26 KD mice with acoustic trauma experienced higher hearing loss than simple noise exposure siblings and nearly had no recovery. Additionally, extensive outer hair cell loss and more severe destruction of the basal organ of Corti were observed in Cx26 KD mice after noise exposure. These data indicate that reduced Cx26 expression in the mature mouse cochlea may increase susceptibility to noise-induced hearing loss and facilitate the cell degeneration in the organ of Corti.

A Multilayer Perceptron Based Smart Pathological Brain Detection System by Fractional Fourier Entropy.

This work aims at developing a novel pathological brain detection system (PBDS) to assist neuroradiologists to interpret magnetic resonance (MR) brain images. We simplify this problem as recognizing pathological brains from healthy brains. First, 12 fractional Fourier entropy (FRFE) features were extracted from each brain image. Next, we submit those features to a multi-layer perceptron (MLP) classifier. Two improvements were proposed for MLP. One improvement is the pruning technique that determines the optimal hidden neuron number. We compared three pruning techniques: dynamic pruning (DP), Bayesian detection boundaries (BDB), and Kappa coefficient (KC). The other improvement is to use the adaptive real-coded biogeography-based optimization (ARCBBO) to train the biases and weights of MLP. The experiments showed that the proposed FRFE + KC-MLP + ARCBBO achieved an average accuracy of 99.53 % based on 10 repetitions of K-fold cross validation, which was better than 11 recent PBDS methods.

NLRP3 inflammasome sequential changes in Staphylococcus aureus-induced mouse model of acute rhinosinusitis.

The NLR pyrin domain containing 3 (NLRP3) inflammasome plays a crucial role in lung disease and may have a similar role in upper respiratory tract inflammation. We therefore constructed a C57BL/6 mouse model of acute rhinosinusitis induced by Staphylococcus aureus and investigated the role of the NLRP3 inflammasome in this model. Mice were classified as non-inoculated group (group A) and inoculated groups (groups B, C, D and E, sacrificed 1, 3, 7 and 14 days after inoculation, respectively). Hematoxylin-eosin staining showed that each group had inflammatory cell infiltration, except group A. The damage of the nasal mucosa was aggravated gradually over time. Western blot and immunofluorescence showed that the structural proteins of the NLRP3 inflammasome (NLRP3, ASC (apoptosis-associated speck-like protein containing CARD), procaspase-1) in groups B, C, D and E were increased gradually. But they were reduced in group B compared with group A, except for NLRP3. Western blot showed that the cleavage fragment of procaspase-1, p20 in groups B, C, D and E was increased gradually. Real-time PCR showed that the corresponding mRNAs of the structural proteins were changed the same as their proteins. IL-1ß mRNA and mature IL-1ß protein were increased gradually in groups A, B, C, D and E. These results indicate that NLRP3 inflammasome activation was associated with the acute rhinosinusitis, and that there was a positive correlation between the expression level of the NLRP3 inflammasome and the severity of acute rhinosinusitis.

[Study on mechanism of thyroid cytotoxicity of ammonium perchlorate].

OBJECTIVE: To investigate the mechanism of thyroid cytotoxicity mechanism of ammonium perchlorate (AP). METHODS: Thyroid cells were cultured in vitro to a certain stage and then exposed to AP (0, 5, 10, 20, 40, and 60 mmol/L) in culture solution; the cultured cells and supernatant were collected. Cell viability was measured by MTT assay; cell apoptosis was determined by flow cytometry; the concentration of thyroglobulin was measured by enzyme-linked immunosorbent assay; the lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, and so on were measured by colorimetry. RESULTS: The cells exposed to 60 mmol/L AP for 12, 24, 48, and 72 h had cell viabilities of 74.93%, 42.26%, 2.66%, and 0.99%, respectively, and the cells exposed to 40 mmol/L AP for 24, 48, and 72 h had cell viabilities of 73.15%, 30.91%, and 3.03%, respectively, all significantly lower than that of the control group (100%)(P < 0.05 or P < 0.01). The overall apoptosis rate of all AP-exposed cells was significantly higher than that of the control group; the cells exposed to 20, 40, and 60 mmol/L AP had early apoptosis rates of 15.70%, 15.84%, and 16.96%, respectively, significantly higher than that of the control group (9.54%)(P < 0.05 or P < 0.01); the cells exposed to 60 mmol/L AP had a late apoptosis rate of 16.54%, significantly higher than that of the control group (6.11%)(P < 0.05 or P < 0.01). The cells exposed to 40 mmol/L AP had a significantly higher LDH activity than the control group (0.70 U/ml vs 0.55 U/ml, P < 0.01). The cells exposed to 5 mmol/L AP had a significantly higher MDA level than the control group (1.08 mmol/L vs 2.36 mmol/L, P < 0.05). CONCLUSION: AP can markedly change the cell morphology and decrease the cell viability of thyroid cells, which may be because AP inhibits cell proliferation, induces cell apoptosis, and destroys cell membranes. However, AP does not result in significant oxidative damage to thyroid cells.

Comparison of protective effects of hesperetin and pectolinarigenin on high-fat diet-induced hyperlipidemia and hepatic steatosis in Golden Syrian hamsters.

A comparative study was conducted to determine whether hesperetin and pectolinarigenin could lower total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) in a high-fat diet (HFD)-induced high lipid model in Golden Syrian hamsters. 48 Golden Syrian hamsters (8 weeks old) were fed with a HFD for 15 days. HFD induced significant increases in plasma TC, TG, LDL, and HDL. Then, these high lipid hamsters were divided into four groups and were administered with 0.5% sodium carboxymethyl cellulose (CMC-Na), hesperetin (100 mg/kg/day), pectolinarigenin (100 mg/kg/day) or atorvastatin (1.0 mg/kg/day), for 7 weeks. It was found that pectolinarigenin treatment resulted in significant reductions in body weight, adiposity index, serum levels of TC, TG and hepatic TC, TG and free fatty acid compared to those in control hamsters with hyperlipidemia (P<0.05). However, hesperetin treatment only caused reductions in plasma TC and hepatic TG levels. Besides, the hamsters treated with pectolinarigenin showed a relatively normal hepatic architecture compared to the hepatic steatosis shown in the control group. Moreover, the expressions of fatty-acid synthase (Fasn) and solute carrier family 27 member 1 (Slc27a1) involved in lipid biosynthesis, were suppressed in the pectolinarigenin-treated groups, and the expression of carnitine palmitoyltransferase 1A (Cpt1a) involved in fatty acid oxidation was increased in the pectolinarigenin-treated group. Taken together, these results suggest pectolinarigenin exerts stronger protective effects against hyperlipidemia and hepatic steatosis than hesperetin, which may involve the inhibition of lipid uptake and biosynthesis.

Recent Research on Municipal Sludge as Soil Fertilizer in China: a Review.

Due to the annual increase in wastewater treatment in most Chinese cities, a major environmental issue has arisen: safe treatment, disposal, and recycling of municipal sludge. Municipal sludge has a high content of carbon and essential nutrients for plant growth; hence, it has gained interest among researchers as a soil fertilizer. This study discusses the potential usage of municipal sludge as soil fertilizer (indicators include nitrogen (N), phosphorus (P), and trace elements) along with its shortcomings and drawbacks (potentially toxic elements (PTEs), organic matter (OM), pathogens, etc.) as well as reviews the latest reports on the role of municipal sludge in land use. The use of municipal sludge as a soil fertilizer is a sustainable management practice and a single application of sludge does not harm the environment. However, repeated use of sludge may result in the accumulation of harmful chemicals and pathogens that can enter the food chain and endanger human health. Therefore, long-term field studies are needed to develop ways to eliminate these adverse effects and make municipal sludge available for agricultural use.

Model-Free Adaptive Control of Hydrometallurgy Cascade Gold Leaching Process with Input Constraints.

Hydrometallurgy technology can directly deal with low grade and complex materials, improve the comprehensive utilization rate of resources, and effectively adapt to the demand of low carbon and cleaner production. A series of cascade continuous stirred tank reactors are usually applied in the gold leaching industrial process. The equations of leaching process mechanism model are mainly composed of gold conservation, cyanide ion conservation, and kinetic reaction rate equations. The derivation of the theoretical model involves many unknown parameters and some ideal assumptions, which leads to difficulty and imprecision in establishing the accurate mechanism model of the leaching process. Imprecise mechanism models limit the application of model-based control algorithms in the leaching process. Due to the constraints and limitations of the input variables in the cascade leaching process, a novel model-free adaptive control algorithm based on compact form dynamic linearization with integration (ICFDL-MFAC) control factor is first constructed. The constraints between input variables is realized by setting the initial value of the input to the pseudo-gradient and the weight of the integral coefficient. The proposed pure data-driven ICFDL-MFAC algorithm has anti-integral saturation ability and can achieve faster control rate and higher control precision. This control strategy can effectively improve the utilization efficiency of sodium cyanide and reduce environmental pollution. The consistent stability of the proposed control algorithm is also analyzed and proved. Compared with the existing model-free control algorithms, the merit and practicability of the control algorithm are verified by the practical leaching industrial process test. The proposed model-free control strategy has advantages of strong adaptive ability, robustness, and practicability. The MFAC algorithm can also be easily applied to control the multi-input multi-output of other industrial processes.