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Rationale: Very-low-density lipoprotein receptor (VLDLR) involves in ocular neovascularization, a major cause of severe vision loss. However, the underlying molecular mechanisms were not completely clarified. Here, we aimed to investigate roles of circular RNAs (circRNAs) in VLDLR-associated ocular neovascularization., Methods: Vldlr knockout (Vldlr-/-, ko), Robo4 knockout (Robo4-/-, ko) and wild-type (WT) mice were used. Mouse model of oxygen induced retinopathy (OIR) and high-throughput sequence were performed to profile the differential expression of circRNA and transcripts. RNase R treatment, Sanger PCR sequencing and quantitative polymerase chain reaction (qPCR) were used to validate candidate circRNAs and their expression patterns. Choroidal sprouting assay ex vivo and laser induction choroid neovascularization were used to determine the expression and functions of QKI/CircSlc17a5 on choroidal neovascularization., Results: In macrophage and ocular tissues derived from Vldlr (Vldlr-/-,Vldlr ko) or Robo4 (Robo4-/-,Robo4 ko) deficiency as well as wild-type (WT) mice, Quaking (Qki) expression was significantly down-regulated in Vldlr deficiency compared to WT and Robo4 deficiency groups. Ectopic VLDLR expression or Reelin stimulation increased expression of QKI in bEnd.3 cells. Circular RNA sequencing uncovered that VLDLR regulated the biogenesis of certain circular RNAs, including the circSlc17a5. The number of Circular RNAs increased in mice treated with OIR. QKI mediated the biogenesis of circSlc17a5, which was an important regulator of choroidal angiogenesis., Conclusion: CircSlc17a5 regulated by VLDLR/QKI plays important roles in the choroidal angiogenesis., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Sepsis is a systemic inflammatory response caused by an infection, which can easily lead to acute lung injury. Quiescin Q6 sulfhydryl oxidase 1 (QSOX1) is a sulfhydryl oxidase involved in oxidative stress and the inflammatory response. However, there are few reports on the role of QSOX1 in sepsis-induced acute lung injury (SALI). In this study, mice model of SALI was constructed by intraperitoneal injection with lipopolysaccharide (LPS). The increased inflammatory response and lactate dehydrogenase activity in bronchoalveolar lavage fluid (BALF) indicated successful modeling. Increased QSOX1 expression was both observed in lung tissues and lung macrophages of sepsis mice accompanied by increased polarization of M1-type macrophages. To explore the role of QSOX1 in the SALI, lentivirus containing QSOX1-specific overexpression or knockdown vectors were used to change QSOX1 expression in LPS-treated RAW264.7 cells. QSOX1 suppressed LPS-induced M1 polarization and further inhibited inflammatory response in RAW264.7 cells. Interestingly, the phosphorylation of epidermal growth factor receptor (EGFR), the promoter of M1 polarization in macrophages, was found to be downregulated upon QSOX1 overexpression in RAW264.7 cells. Mechanically, the binding of QSOX1 to EGFR protein promoted EGFR ubiquitination and degradation, thereby down-regulating EGFR phosphorylation. Moreover, inhibiting EGFR expression or its phosphorylation restored the impact of QSOX1 silencing on M1 polarization and inflammation in the LPS-treated RAW264.7 cells. In summary, QSOX1 may exert anti-inflammatory effects in SALI by inhibiting EGFR phosphorylation-mediated M1 macrophage polarization. This presented a potential target for the treatment and prevention of SALI., Competing Interests: Declaration of Competing Interest none, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In-field or in-margin recurrence after partial gland cryosurgical ablation (PGCA) of prostate cancer (PCa) remains a limitation of the paradigm. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real time, label-free, high-resolution microscopic images of unprocessed, un-sectioned tissue which can be interpreted by humans or artificial intelligence (AI). We evaluated surgical team and AI interpretation of SRH for real-time pathologic feedback in the planning and treatment of PCa with PGCA., Methods: About 12 participants underwent prostate mapping biopsies during PGCA of their PCa between January and June 2022. Prostate biopsies were immediately scanned in a SRH microscope at 20 microns depth using 2 Raman shifts to create SRH images which were interpreted by the surgical team intraoperatively to guide PGCA, and retrospectively assessed by AI. The cores were then processed, hematoxylin and eosin stained as per normal pathologic protocols and used for ground truth pathologic assessment., Results: Surgical team interpretation of SRH intraoperatively revealed 98.1% accuracy, 100% sensitivity, 97.3% specificity for identification of PCa, while AI showed a 97.9% accuracy, 100% sensitivity and 97.5% specificity for identification of clinically significant PCa. 3 participants' PGCA treatments were modified after SRH visualized PCa adjacent to an expected MRI predicted tumor margin or at an untreated cryosurgical margin., Conclusion: SRH allows for accurate rapid identification of PCa in PB by a surgical team interpretation or AI. PCa tumor mapping and margin assessment during PGCA appears to be feasible and accurate. Further studies evaluating impact on clinical outcomes are warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Soil parent material is the second most influential factor in pedogenesis, influencing soil properties and microbial communities. Different assembly processes shape diverse functional microbial communities. The question remains unresolved regarding how these ecological assembly processes affect microbial communities and soil functionality within soils on different parent materials. We collected soil samples developed from typical parent materials, including basalt, granite, metamorphic rock, and marine sediments across soil profiles at depths of 0-20, 20-40, 40-80, and 80-100 cm, within rubber plantations on Hainan Island, China. We determined bacterial community characteristics, community assembly processes, and soil enzyme-related functions using 16S rRNA high-throughput sequencing and enzyme activity analyses. We found homogeneous selection, dispersal limitation, and drift processes were the dominant drivers of bacterial community assembly across soils on different parent materials. In soils on basalt, lower pH and higher moisture triggered a homogeneous selection-dominated assembly process, leading to a less diverse community but otherwise higher carbon and nitrogen cycling enzyme activities. As deterministic process decreased, bacterial community diversity increased with stochastic process. In soils on marine sediments, lower water, carbon, and nutrient content limited the dispersal of bacterial communities, resulting in higher community diversity and an increased capacity to utilize relative recalcitrant substrates by releasing more oxidases. The r-strategy Bacteroidetes and genera Sphingomonas, Bacillus, Vibrionimonas, Ochrobactrum positively correlated with enzyme-related function, whereas k-strategy Acidobacteria, Verrucomicrobia and genera Acidothermus, Burkholderia-Caballeronia-Paraburkholderia, HSB OF53-F07 showed negative correlations. Our study suggests that parent material could influence bacterial community assembly processes, diversity, and soil enzyme-related functions via soil properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The approximately 70% 12-month relapse in children experiencing the initial episode of steroid-sensitive nephrotic syndrome (SSNS) is a significant concern, with over 50% developing frequent relapses or steroid-dependent nephrotic syndrome (FRNS/SDNS). There is a lack of strategies to reduce relapse after the onset. Whether early administration of rituximab, which effectively reduces relapses in FRNS/SDNS, may be a solution has not been evaluated., Methods: A prospective, multicenter, open-label, single-arm trial was conducted in China, with a 12-month follow-up. Children aged 1 to 18 years with the first episode of nephrotic syndrome (NS) were screened for eligibility. Proteinuria was evaluated daily using dipsticks. A dose of 375 mg/m 2 of rituximab was intravenously infused within 1 week after achieving corticosteroid-induced remission. The main outcome was 12-month relapse-free survival., Results: Out of the initially 66 children screened, 44 were enrolled and received rituximab, with all but 1 participant completing the 12-month follow-up. The median age at diagnosis was 4.3 years (interquartile range [IQR]: 3.4-5.9), and 33 (77%) of the participants were male. In the rituximab group, the 12-month relapse-free survival was significantly higher compared to historical controls (32 of 43 [74.4%] vs. 10 of 33 [30.3%]; P  < 0.001; hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.80-7.81). The post hoc analysis revealed a higher 24-month relapse-free survival and a lower incidence of FRNS/SDNS at the 12-month follow-up. Treatment with rituximab was well-tolerated., Conclusion: Our findings support that early administration of rituximab may be associated with a higher 12-month relapse-free survival and a reduced incidence of FRNS/SDNS in children experiencing the initial episode of SSNS., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

The magnetic CuFe 2 O 4 /MnO 2 heterojunctions were prepared by hydrothermal method, and the effect of different reaction temperature on the physicochemical properties and catalytic activity was investigated. The CuFe 2 O 4 /MnO 2 heterojunctions prepared at 100 °C can effectively activate peroxymonosulfate (PMS) at multiple application scenarios for degradation and mineralization of tetracycline, o-nitrophenol and ceftriaxone sodium under indoor light, visible light and dark condition. Additionally, the CuFe 2 O 4 /MnO 2 -PMS system showed high catalytic activity and anti-interference ability for degradation of pharmaceutical pollutants in natural water bodies and industrial wastewater. The TC removal efficiency in Qianhu Lake water, Ganjiang River water and tap water was about 88%, 92% and 89%, respectively. The CuFe 2 O 4 /MnO 2 -PMS system is also effective for actual pharmaceutical wastewater treatment with 77.9% of COD removal efficiency. Interestingly, the reactive species of CuFe 2 O 4 /MnO 2 -PMS system under visible light are different from those in dark condition, and the different catalytic mechanisms at multiple application scenarios were proposed. This work provides new insights into mechanism exploration of heterojunction catalyst for PMS activation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Citri Sarcodactylis Fructus (CSF) is widely used as food raw material and traditional Chinese medicine. Fingerprints of different fractions of CSF were established for spectrum-effect relationship analysis, and the main compounds were identified by UHPLC Quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS). The antitussive effect was evaluated using a classical mouse model of cough induced by ammonia water. One-way ANOVA was used to determine differences in efficacy. The potential active compounds were screened by spectrum-effect relationship with grey relational degree analysis (GRA), Pearson bivariate correlation analysis (Pearson's), and partial least squares analysis (PLS) analyses. Differential metabolites associated with cough in serum were screened and identified using orthogonal partial least squares-discriminant analysis, HMDB database, and UHPLC-Q/Orbitrap HRMS. Metabolic pathway analysis was performed using MetaboAnalyst 5.0. Results indicate that 70 % ethanol elution fraction (70 % EF) is the major active fraction, and 8 components were identified to possess antitussive effects. Metabolomic analysis showed that 19 metabolites are potential biomarkers related to cough, and 70 % EF can remarkable restore 13 of them to normal levels (P < 0.05). These biomarkers are mainly involved in glycerophospholipid metabolism and sphingolipid metabolism. This study aims to reveal the main pharmacodynamic active sites and potential active ingredients of CSF's antitussive effect. In addition, metabolomics was used to preliminarily elucidate the in-vivo regulatory mechanism of the antitussive effect of the 70 % EF of CSF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this study, artificial humic acid (AHA) was produced from rice straw at room temperature. The response surface methodology was used to investigate the response of artificial humic acid to time, liquid-solid ratio, and KOH concentration. The optimal reaction conditions were determined: reaction time of 2 h, liquid-solid ratio of 6, and KOH concentration of 1.5 mol/L. The artificial humic acid content under these conditions was 32.29 g/L, which satisfied the Chinese agricultural industry standard for water-soluble humic acid fertilizers (humic acid content ≥30 g/L). Compared with chemical fertilizers, artificial humic acid fertilizer promoted chard growth and increased soil organic matter and humic acid. The stability of artificial humic acid was better, with a retention rate of 60.47 % in the soil. Water-soluble humic acid fertilizer also promoted chard growth by increasing the relative abundance of growth-promoting bacteria such as Glutamicibacter and Pseudomonas and, as well as growth-promoting fungi such as Mortierella. The application of water-soluble humic acid fertilizers has implications for both soil improvement and the reduction of agricultural carbon emissions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polychlorinated biphenyls (PCBs) are ubiquitous persistent organic pollutants that cause harmful effects on environmental safety and human health. There is an urgent need to develop an intelligent method for PCBs sensing. In this work, we proposed a logic gate biosensing platform for simultaneous detection of multiple PCBs. 2,3',5,5'-tetrachlorobiphenyl (PCB72) and 3,3',4,4'-tetrachlorobiphenyl (PCB77) were used as the two inputs to construct biocomputing logic gates. We used 0 and 1 to encode the inputs and outputs. The aptamer was used to recognize the inputs and release the trigger DNA. A catalytic hairpin assembly (CHA) module is designed to convert and amplify each trigger DNA into multiple programmable DNA duplexes, which initiate the trans-cleavage activity of CRISPR/Cas12a for the signal output. The activated Cas12 cleaves the BHQ-Cy5 modified single-stranded DNA (ssDNA) to yield the fluorescence reporting signals. In the YES logic gate, PCB72 was used as the only input to carry out the logic operation. In the OR, AND, and INHIBIT logic gates, PCB72 and PCB77 were used as the two inputs. The output signals can be visualized by the naked eye under UV light transilluminators or quantified by a microplate reader. Our constructed biosensing platform possesses the merits of multiple combinations of inputs, intuitive digital output, and high flexibility and scalability, which holds great promise for the intelligent detection of different PCBs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Renal tumor biopsy requires adequate tissue sampling to aid in the investigation of small renal masses. In some centers the contemporary nondiagnostic renal mass biopsy rate may be as high as 22% and may be as high as 42% in challenging cases. Stimulated Raman Histology (SRH) is a novel microscopic technique which has created the possibility for rapid, label-free, high-resolution images of unprocessed tissue which may be viewed on standard radiology viewing platforms. The application of SRH to renal biopsy may provide the benefits of routine pathologic evaluation during the procedure, thereby reducing nondiagnostic results. We conducted a pilot feasibility study, to assess if renal cell carcinoma (RCC) subtypes may be imaged and to see if high-quality hematoxylin and eosin (H&E) could subsequently be generated., Methods/materials: An 18-gauge core needle biopsy was taken from a series of 25 ex vivo radical or partial nephrectomy specimens. Histologic images of the fresh, unstained biopsy samples were obtained using a SRH microscope using 2 Raman shifts: 2,845 cm -1  and 2,930 cm -1 . The cores were then processed as per routine pathologic protocols. The SRH images and hematoxylin and eosin (H&E) slides were then viewed by a genitourinary pathologist., Results: The SRH microscope took 8 to 11 minutes to produce high-quality images of the renal biopsies. Total of 25 renal tumors including 1 oncocytoma, 3 chromophobe RCC, 16 clear cells RCC, 4 papillary RCC, and 1 medullary RCC were included. All renal tumor subtypes were captured, and the SRH images were easily differentiated from adjacent normal renal parenchyma. High quality H&E slides were produced from each of the renal biopsies after SRH was completed. Immunostains were performed on selected cases and the staining was not affected by the SRH image process., Conclusion: SRH produces high quality images of all renal cell subtypes that can be rapidly produced and easily interpreted to determine renal mass biopsy adequacy, and on occasion, may allow renal tumor subtype identification. Renal biopsies remained available to produce high quality H&E slides and immunostains for confirmation of diagnosis. Procedural application has promise to decrease the known rate of renal mass nondiagnostic biopsies, and application of convolutional neural network methodology may further improve diagnostic capability and increase utilization of renal mass biopsy among urologists., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We successfully constructed several molecular logic gates using heavy metal ions as inputs based on catalytic hairpin assembly (CHA) and CRISPR-Cas12a. The corresponding DNAzymes were used to recognize heavy metal ions (Hg 2+ , Cd 2+ , Pb 2+ , and Mn 2+ ). The specific cleavage between heavy metal ions and DNAzymes leads to the release of the trigger DNA, which can be used to activate CHA through logic computation. The CHA-generated DNA duplexes contain the protospacer adjacent motifs (PAM) sequence, which can be distinguished by CRISPR-Cas12a. The hybridization interactions between the duplexes and gRNA will activate the trans-cleavage capability of Cas12a, which can cleave the single-stranded DNA (ssDNA) reporter. The separation of the fluorescence group and quench group in ssDNA will generate a high fluorescence signal for readout. Using Hg 2+ and Cd 2+ as the two inputs, several basic logic gates were constructed, including OR, AND, and INHIBT. Using Hg 2+ , Cd 2+ , Pb 2+ , and Mn 2+ as the four inputs, cascaded logic gates were further fabricated. With the advantages of scalability, versatility, and logic computing capability, our proposed molecular logic gates can provide an intelligent sensing system for heavy metal ions monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Two anaerobic reactors with and without Ca 2+ were operated at 35 °C to investigate the effects of different H 2 /CO 2 ratios on products and microbial communities. Through the investigation of various parameters, it was shown that the change of pH triggered by the variations of H 2 /CO 2 is the decisive factor affecting the product selection in anaerobic fermentation system. During the biosynthesis of ATP for cell growth and reproduction, protons (H + ) were pumped from extracellular to intracellular by proton pump, which caused an increase of intrinsic pH of fermentative system. When the pH below 9.5, the methanogenic pathway was more prevalent. While the pH above 10.0 was conducive to the homoacetogenesis. Microbial community analysis showed that with the changes of H 2 /CO 2 ratio, a turnover had occurred. When the ratio of H 2 /CO 2 was 4, the main methanogen was Methanobacterium with the dominant interspecies electron transfer bacteria (IETB) of Thermovirga and DMER64. The turnover of microbial community occurred when the H 2 /CO 2 ratio was 4.5 and 4.25. The dominant acetogenic microorganisms were norank&#95;o&#95;Clostridia&#95;UCG-014 (homoacetogen) and Natronincola (obligately alkaliphilic acetogen). When the H 2 /CO 2 ratio returned to 4, the dominant methanogens were hydrotropic Methanobacterium and Methanobrevibacter with four interspecies electron transfer bacteria including DMER64, Thermovirga, Dechlorobacter and Achromobacter., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A fluorescent biosensor was developed for Cd 2+ detection based on a Cd 2+ -fueled wheel DNAzyme walker. Cd 2+ can activate the wheel to roll along the DNA walking tracks through DNAzyme cleavage and toehold-mediated strand displacement. The substrate strand was modified with BHQ and Cy5. Through continuous cleavage reactions toward the substrate strands, a high fluorescence signal can be obtained. The biosensor is ultrasensitive, and the detection limit is 0.2 pM (S/N = 3). The fluorescent assay is robust and has been applied to the determination of Cd 2+ in real water samples with good accuracy and reliability. Using Cd 2+ , Pb 2+ , and Hg 2+ as the three inputs, we also construct a concatenated AND logic gate. The input combination of (111) can produce an output of 1. Other input combinations produce an output of 0. Our proposed detection platform and logic system hold great promise for the ultrasensitive and intelligent sensing of different heavy metal ions in water samples., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We successfully constructed several cascaded molecular logic gates (2INHIBIT-2AND, 2AND-2OR, and 2OR-2INHIBIT) using three different antibiotics as the inputs. In the presence of kanamycin (KAN), chloramphenicol (CHL), or oxytetracycline (OXY), the aptamer-antibiotic recognition will release the trigger DNA to active the hairpin DNA hybridization. Exonuclease III (Exo III)-mediated catalysis reaction was introduced in the logic system to generate Mg 2+ -dependent DNAzyme, which was used to cleave the fluorescence signal reporter probe. For input, the presence and absence of the antibiotic was defined as 1 and 0, respectively. For output, the fluorescence intensity higher or lower than the threshold value was defined as 1 and 0, respectively. In the 2INHIBIT-2AND logic circuit, the 101 input combination generates an output of 1 and other input combinations generate an output of 0. In the 2AND-2OR logic circuit, the input combinations of 001, 011, 110, 101, and 111 generate an output of 1 and other input combinations generate an output of 0. In the 2OR-2INHIBIT logic circuit, the input combinations of 010, 100, and 110 generate an output of 1 and other input combinations generate an output of 0. Our constructed logic system exhibits high selectivity and can work even in complex water samples. With the advantages of multiple biocomputation capabilities, high flexibility, and easy scalability, this logic gate system provides a new analytical method for the intelligent detection of different antibiotics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Primary Coenzyme Q10 deficiency is a rare mitochondriopathy with a wide spectrum of organ involvement, including steroid-resistant nephrotic syndrome mainly associated with disease-causing variants in the genes COQ2, COQ6 or COQ8B. We performed a systematic literature review, PodoNet, mitoNET, and CCGKDD registries queries and an online survey, collecting comprehensive clinical and genetic data of 251 patients spanning 173 published (47 updated) and 78 new cases. Kidney disease was first diagnosed at median age 1.0, 1.2 and 9.8 years in individuals with disease-causing variants in COQ2, COQ6 and COQ8B, respectively. Isolated kidney involvement at diagnosis occurred in 34% of COQ2, 10.8% of COQ6 and 70.7% of COQ8B variant individuals. Classic infantile multiorgan involvement comprised 22% of the COQ2 variant cohort while 47% of them developed neurological symptoms at median age 2.7 years. The association of steroid-resistant nephrotic syndrome and sensorineural hearing loss was confirmed as the distinctive phenotype of COQ6 variants, with hearing impairment manifesting at average age three years. None of the patients with COQ8B variants, but 50% of patients with COQ2 and COQ6 variants progressed to kidney failure by age five. At adult age, kidney survival was equally poor (20-25%) across all disorders. A number of sequence variants, including putative local founder mutations, had divergent clinical presentations, in terms of onset age, kidney and non-kidney manifestations and kidney survival. Milder kidney phenotype was present in those with biallelic truncating variants within the COQ8B variant cohort. Thus, significant intra- and inter-familial phenotype variability was observed, suggesting both genetic and non-genetic modifiers of disease severity., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Primary Coenzyme Q10 (CoQ 10 ) deficiency is an ultra-rare disorder caused by defects in genes involved in CoQ 10 biosynthesis leading to multidrug-resistant nephrotic syndrome as the hallmark kidney manifestation. Promising early results have been reported anecdotally with oral CoQ 10 supplementation. However, the long-term efficacy and optimal prescription remain to be established. In a global effort, we collected and analyzed information from 116 patients who received CoQ 10 supplements for primary CoQ 10 deficiency due to biallelic pathogenic variants in either the COQ2, COQ6 or COQ8B genes. Median duration of follow up on treatment was two years. The effect of treatment on proteinuria was assessed, and kidney survival was analyzed in 41 patients younger than 18 years with chronic kidney disease stage 1-4 at the start of treatment compared with that of an untreated cohort matched by genotype, age, kidney function, and proteinuria. CoQ 10 supplementation was associated with a substantial and significant sustained reduction of proteinuria by 88% at 12 months. Complete remission of proteinuria was more frequently observed in COQ6 disease. CoQ 10 supplementation led to significantly better preservation of kidney function (5-year kidney failure-free survival 62% vs. 19%) with an improvement in general condition and neurological manifestations. Side effects of treatment were uncommon and mild. Thus, our findings indicate that all patients diagnosed with primary CoQ 10 deficiency should receive early and life-long CoQ 10 supplementation to decelerate the progression of kidney disease and prevent further damage to other organs., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

In this study, microbes were added to food waste compost in order to investigate the bioaugmentation mechanism of Humic acid (HA) formation. Thermogravimetric analysis, structural equation model, Fourier transform infrared spectroscopy and statistical analysis were utilized to explain the bioaugmentation mechanism. The results showed that bioaugmentation increased humification rate and degree. Bioaugmentation not only promoted the formation of aromatic structures and CC bonds but also brought different change orders of functional groups in HA. The HA obtained in bioaugmentation group (BA, 7.51 g/kg) was significantly higher compared to the control group (CK, 2.37 g/kg). Similarly, the HA/FA of BA (1.90) was also higher than that of CK (0.62), and peaked at 2.34 on day 40. The polyphenol humification pathway played a major role regardless of the addition of inoculant. However, the exogenous microbes promoted protein and carbohydrate degradation in the initial stage, and the abundance of precursors (amino acids and reducing sugars) enhanced both Maillard and polyphenol humification pathways. When polyphenol was insufficient in later stage, bioaugmentation mainly embodied in the strengthening of Maillard humification pathway. This finding benefited the practice of directional humification process of food waste composting., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The objective of this study was to investigate the effect of polysaccharides from Ostrea rivularis (ORP) relieving reproductive damage by regulating autophagy. The results showed that ORP intervention could alleviate the pathological changes of the testis and alleviate oxidative stress which were caused by cyclophosphamide (CTX) in vivo, including improve sperm symptoms and rise testosterone level. Reduced level of autophagy after ORP intervention was observed by transmission electron microscopy (TEM), which implied that ORP might regulate cell autophagy. In vitro experiments showed that ORP could alleviate the damage of TM4 cells induced by H 2 O 2 , reduce the level of intracellular ROS and the content of MDA. Autophagy-related protein expressions of p62, LC3, Beclin-1 before and after 3-MA inhibitor intervention were also proved that ORP could regulate autophagy. Overall, these results confirmed that ORP could reduce reproductive damage related to autophagy., (Copyright © 2022. Published by Elsevier B.V.)

Background: Sepsis is the leading cause of mortality in children. Several scoring systems are used to predict outcome and mortality for pediatric patients with sepsis, but how they compare to each other in terms of sensitivity and specificity is unclear., Methods: The systematic literature review was performed following PRISMA guidelines. Publically accessible search engines and study databases such as PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), and Google Scholar were scanned for articles published from January 1990 to March 2021 using relevant key words. All relevant studies were analyzed separately by two reviewers. A random-effects model was used to calculate the pooled sensitivity and pooled specificity with a 95% confidence interval (CI). Heterogeneity was evaluated using I 2 , which estimates the percentage of variation between study results due to heterogeneity rather than sampling error., Results: Eleven studies met inclusion criteria and evaluated the SOFA scoring system. The pooled sensitivity, specificity, and SROC for prediction of mortality were 83% (95% CI: 76%-88%), 72% (95% CI: 60%-81%), and 85% (95% CI: 82%-88%), respectively. Six studies examined the SIRS system. Pooled sensitivity, specificity, and SROC were 80% (95% CI: 64%-90%), 36% (95% CI: 23%-51%), and 59% (95% CI: 55%-63%), respectively., Conclusion: This meta-analysis shows that SOFA was superior to SIRS for predicting mortality in PICU patients with sepsis. Additional prospective multi-centric studies are needed to better evaluate and validate this finding., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Urban particulate matter forecast is an important part of air pollution early warning and control management, especially the forecast of fine particulate matter (PM 2.5 ). However, the existing PM 2.5 concentration prediction methods cannot effectively capture the complex nonlinearity of PM 2.5 concentration, and most of them cannot accurately simulate the temporal and spatial dependence of PM 2.5 concentration at the same time. In this paper, we propose an attention-based parallel network (APNet), which can extract short-term and long-term temporal features simultaneously based on the attention-based CNN-LSTM multilayer structure to predict PM 2.5 concentration in the next 72 h. Firstly, the Maximum Information Coefficient (MIC) is designed for spatiotemporal correlation analysis, fully considering the linearity, non-linearity and non-functionality between the data of each monitoring station. The potential inherent features of the input data are effectively extracted through the convolutional neural network (CNN). Then, an optimized long short-term memroy (LSTM) network captures the short-term mutations of the time series. An attention mechanism is further designed for the proposed model, which automatically assigns different weights to different feature states at different time stages to distinguish their importance, and can achieve precise temporal and spatial interpretability. In order to further explore the long-term time features, we propose a Bi-LSTM parallel module to extract the periodic characteristics of PM 2.5 concentration from both previous and posterior directions. Experimental results based on a real-world dataset indicates that the proposed model outperforms other existing state-of-the-art methods. Moreover, evaluations of recall (0.790), precision (0.848) (threshold: 151 μg/m 3 ) for 72 h prediction also verify the feasibility of our proposed model. The methodology can be used for predicting other multivariate time series data in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Petal-like ZnS-SnS 2 heterojunctions with Z-scheme band alignment were prepared by one-pot solvothermal strategy. The optimal (1:1) ZnS-SnS 2 can degrade 93.46 % of tetracycline and remove 73.9 % COD of pharmaceutical wastewater under visible-light irradiation due to the efficient production of H, O 2 - , h + and OH. The toxicity evaluation by ECOSAR prediction and the growth of E. coli indicates efficient toxicity reduction of tetracycline by photocatalysis and the non-toxicity of ZnS-SnS 2 . The attacked sites on tetracycline by reactive species were analyzed according to Fukui index, and two degradation pathways of tetracycline were inferred via the identification of intermediate products. Tetracycline degradation efficiency and the energy consumption in different water bodies were compared, and it was found that the electrical energy per order (EE/O) was the lowest in Ganjiang River. The valence band offset (ΔE VBO ) and conduction band offset (ΔE CBO ) of ZnS-SnS 2 were 1.02 eV and 0.22 eV, respectively. The probable photocatalytic mechanism of ZnS/SnS 2 heterojunctions with Z-scheme band alignment based on ΔE VBO and ΔE CBO was first presented., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The present study aimed to investigate the expression and co-localization of stomatin-like protein-1 (STOML1) and stomatin-like protein-2 (STOML2) in oral squamous cell carcinoma (OSCC) tissues in situ and evaluate their pathologic roles in OSCC., Study Design: STOML1 and STOML2 in human OSCC tissues (n = 109) and normal oral/paracancerous tissues (n = 19) were detected by using multiple immunohistochemistry (IHC) staining. Positive staining scores and clinicopathologic features during the OSCC process were analyzed., Results: STOML1 and STOML2 were significantly overexpressed in OSCC tissues compared with normal oral tissue/paracancerous tissues (P < .0001 and P < .0001, respectively). Furthermore, both STOML1 and STOML2 were positively associated with pathologic tumor (T) stages. Positive signals of both STOML1 and STOML2 were mainly localized to the cell membrane and the cytoplasm, whereas those of STOML1 were also expressed in the cell nucleus., Conclusions: Our results indicated that overexpression of STOML1 and STOML2 was significantly associated with T1 and T2 stages of OSCC. STOML1 and STOML2 were mainly co-localized at the cell membrane and the cytoplasm. These findings suggested that either STOML1 or STOML2 may play critical roles in OSCC development and may serve as potential diagnostic biomarkers and therapeutic targets., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The ecological toxicity of photocatalysts and toxicity reduction of Cr(VI) have attracted much attention. The development of environmentally-friendly photocatalysts with adsorption and internal hole-scavenging capacity for toxicity reduction of aqueous Cr(VI) via facile preparation method is desirable. In this study, visible-light-active BiOCl x Br 1-x , BiOCl x I 1-x and BiOBr x I 1-x solid solutions were prepared by simple solvothermal strategy. The BiOCl 0.3 Br 0.7 , BiOCl 0.7 I 0.3 and BiOBr 0.7 I 0.3 solid solutions exhibited excellent adsorption capacity and photoreduction ability. The removal efficiency of Cr(VI) by BiOCl 0.3 Br 0.7 was 97.7% within 60 min. BiOCl 0.7 I 0.3 and BiOBr 0.7 I 0.3 can remove Cr(VI) almost completely within less than 30 min, which were much higher than those by BiOCl (81.6%) and BiOBr (67.4%) due to joint effect of adsorption and photoreduction. More importantly, the toxicity evaluation confirmed nontoxicity of BiOCl x Br 1-x , BiOCl x I 1-x and BiOBr x I 1-x , and rapid toxicity elimination process of Cr(VI)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Postmortem tenderization is induced by the cooperation of various related enzymes. In this study, CaCl2 and MDL-28170 (Cbz-Val-Phe-H, a calpain inhibitor) were used to regulate the postmortem tenderization process of duck breast muscle. Then the relationship between muscle tenderness change and different enzymes was investigated. At day 0, day 1, and day 4 of the postmortem ageing, the shear force, myofibril fragmentation index (MFI), enzymatic activities of calpains, cathepsin-B, caspase-3, Na+/K+-ATPase, and Ca2+-ATPase were respectively determined. The results showed that duck muscle tenderness could be significantly raised by CaCl2 and reduced by MDL-28170, respectively (P < 0.05). The CaCl2 treatment did not promote the calpains activity as predicted (P > 0.05), but significantly up-regulated the activity of cathepsin-B (P < 0.05). The MDL-28170 significantly inhibited the activity of the calpain system at day 1 (P < 0.05) and raised the activities of the selected 3 apoptosis-related enzymes, including caspase-3, Na+/K+-ATPase, and Ca2+-ATPase, at both day 1 and day 4 (P < 0.05). These data indicated that in duck, the calpain system could be well activated after death, and cathepsin-B might also play an important role in postmortem muscle tenderization. The caspase-3, Na+/K+-ATPase, and Ca2+-ATPase probably have no significant effects on duck muscle tenderness. It might provide useful information for duck production and further research on postmortem muscle tenderization., (© 2019 Poultry Science Association Inc.)

Sulfated polysaccharide (SP) extracted from sea algae has been used to chelate with ferric to yield polysaccharide iron complex (SPIC). The main active components and groups, monosaccharide composition, molecular weight and anti-oxidative capability were studied comparatively. Results showed that both have good stability and no free ferric ions in SPIC, and no significant difference in total polysaccharide content while sulfate and protein contents lowering and iron content increasing. Fourier-transform infrared (FTIR) spectra indicated further that iron was chelated in polysaccharide chain. Gas chromatograph (GC) showed that the major monosaccharides were fucose, mucose and glucose with molecular ratio of 10:3.8:3.5 in SPIC and 10:8.4:7.5 in SP. MW of SP and SPIC varied no more at 231,3 kD and 237.2 kD respectively using high-performance liquid chromatography (HPLC). Both had hydroxyl radicals scavenging effects in vitro while SPIC showed stronger effects. Comparing oxygen consumption with control PMA-differentiated cells, both took longer time to achieve higher platform and SPIC showed stronger effects than SP. Fluorescence extensity of intracellular ROS showed that SP could reduce the ROS generation while SPIC enhances the effect. The results revealed that the main active components and antioxidant activity exhibit differentiation after SP chelating with ferric., (Copyright © 2018. Published by Elsevier B.V.)

Octahedral CdS/SnIn 4 S 8 nano-heterojunctions were fabricated by a facile and simple one-step in situ hydrothermal method, and the molar ratio of CdS to SnIn 4 S 8 was optimized. The optimal (0.5:1)CdS/SnIn 4 S 8 heterojunctions exhibit the highest visible-light photocatalytic activity with 97.1% degradation efficiency of 2-nitrophenol in 120min, which is much higher than those of individual CdS and SnIn 4 S 8 . The enhanced photocatalytic performance could be attributed to the effective separation and transfer of photogenerated charges originating from the well-matched band gap structures. Of special significance is that (0.5:1)CdS/SnIn 4 S 8 can effectively mineralize 2-nitrophenol and real pharmaceutical wastewater. Moreover, CdS/SnIn 4 S 8 nano-heterojunctions show excellent reusability in five cycles due to the stable surface composition and chemical valence state., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Metal sulfides are promising photocatalysts for efficient removal of organic pollutants in wastewater. However, the practical application of these catalysts is limited due to the fast recombination of charge carriers and poor catalyst stability. In this study, ternary reduced graphene oxide/SnS 2 /ZnFe 2 O 4 (rGO/SnS 2 /ZnFe 2 O 4 ) composites were synthesized by a hydrothermal process, and rGO content was optimized. The surface morphology, crystal structure, optical and electrochemical properties of rGO/SnS 2 /ZnFe 2 O 4 composites were characterized. The adsorption capacity and visible-light photocatalytic activity of rGO/SnS 2 /ZnFe 2 O 4 were influenced by rGO content with results revealing an optimal rGO content of 7wt.%. The 7% rGO/SnS 2 /ZnFe 2 O 4 composite demonstrated the highest visible-light photocatalytic activity with almost 100% 2-nitrophenol removal, which could be attributed to the efficient charge separation, and the formation of O 2 - , h + and a few OH radicals. The possible photocatalytic mechanism of rGO/SnS 2 /ZnFe 2 O 4 composites was also provided based on the role of rGO and the energy bands of SnS 2 and ZnFe 2 O 4 . Moreover, rGO/SnS 2 /ZnFe 2 O 4 composites exhibit excellent reusability without an obvious decline in the photocatalytic activity after four degradation-regeneration cycles. The results indicate that ternary rGO/SnS 2 /ZnFe 2 O 4 composites have good prospect in practical removal of organic pollutants in wastewater due to high efficiency and excellent stability., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Cold-inducible RNA-binding protein (CIRP) is a pro-inflammatory cytokine. We determined whether serum or synovial fluid concentrations are associated with severity in osteoarthritis (OA)., Methods: CIRP concentrations in serum and synovial fluid from 156 knee OA patients and serum from 156 controls were determined. The Kellgren and Lawrence (KL) grade, Lequesne index and Western Ontario McMaster University Osteoarthritis Index (WOMAC) pain score were used to assess radiographic, clinical severity and pain severity respectively. Their scores were dichotomized based on their median values., Results: OA patients had similar serum CIRP concentrations compared to controls. In OA patients, CIRP concentrations in synovial fluid were dramatically higher compared to, but not correlated with paired serum samples. CIRP concentrations in synovial fluid were significantly correlated with synovial fluid or serum C-reactive protein, tumor necrosis factor- alpha and interleukin-6 concentrations, KL grade, Lequesne index and WOMAC pain score. Synovial fluid CIRP concentrations were independently related to the KL grade>2, Lequesne index >13 and WOMAC pain score>12. Under receiver operating characteristic curves, Synovial fluid CIRP concentrations significantly predicted them., Conclusions: Increased synovial fluid CIRP concentrations were closely associated with the severity, substantializing CIRP as a potential marker for synovial inflammation of OA., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Melanocyte stem cells (McSCs) are the origin of melanocytes that are periodically refreshed in skin and hair follicle. Previously, we reported that Wnt3a could promote melanogenesis, but the mechanism of McSCs activation remains unclear., Objective: We aimed to illustrate the roles of Wnt/ß-catenin signaling pathway during McSC activation., Methods: Adenovirus-mediated overexpression of Wnt3a and Wnt10b were used. In vitro experiments were performed on the immortalized melanocyte progenitor cell line iMC23, wheres in vivo experiments were performed in Dct-LacZ mice. Immunofluorescence and western blot were used to determine the protein expression., Results: Wnt3a promotes the differentiation and melanogenesis of iMC23, by activating Wnt/β-catenin signaling pathway. Wnt3a induces hair follicle regeneration and McSC activation. Detailed analysis indicats that Wnt3a activated Wnt/β-catenin signaling pathway, thus promoting the differentiation of McSCs during this process. Wnt10b, another canonical Wnt signaling ligand, induces hair follicle regeneration and McSC activation as well., Conclusion: Wnt/β-catenin signaling pathway activates McSCs both in vitro and in vivo., (Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Introduction: There is increasing interest in using imaging in the detection and localization of prostate cancer (PCa). Both multiparametric magnetic resonance imaging (mpMRI) and HistoScanning (HS) have been independently evaluated in the detection and localization of PCa. We undertook a prospective, blinded comparison of mpMRI and HS for cancer localization among men undergoing radical prostatectomy., Methods: Following approval by the institutional review board, men scheduled to undergo radical prostatectomy, who had previously undergone mpMRI at our institution, were offered inclusion in the study. Those consenting underwent preoperative HS following induction of anesthesia; mpMRI, HS, and surgical step-section pathology were independently read by a single radiologist, urologist, and pathologist, respectively, in a blinded fashion. Disease maps created by each independent reader were compared and evaluated for concordance by a 5 persons committee consisting of 2 urologists, 2 pathologists, and 1 radiologist. Logistic regression for correlated data was used to assess and compare mpMRI and HS in terms of diagnostic accuracy for cancer detection. Generalized estimating equations based on binary logistic regression were used to model concordance between reader opinion and the reference standard assessment of the same lesion site or region as a function of imaging modality., Results: Data from 31/35 men enrolled in the trial were deemed to be evaluable. On evaluation of cancer localization, HS identified cancer in 36/78 (46.2%) regions of interest, as compared with 41/78 (52.6%) on mpMRI (P = 0.3968). The overall accuracy, positive predictive value, negative predictive value, and specificity for detection of disease within a region of interest were significantly better with mpMRI as compared with HS. HS detected 36/84 (42.9%) cancer foci as compared with 42/84 (50%) detected by mpMRI (P = 0.3678). Among tumors with Gleason score>6, mpMRI detected 19/22 (86.4%) whereas HS detected only 11/22 (50%, P = 0.0078). Similarly, among tumors>10mm in maximal diameter, mpMRI detected 28/34 (82.4%) whereas HS detected only 19/34 (55.9%, P = 0.0352)., Conclusion: In our institution, the diagnostic accuracy of HS was inferior to that of mpMRI in PCa for PCa detection and localization. Although our study warrants validation from larger cohorts, it would suggest that the HS protocol requires further refinement before clinical implementation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We assessed changes in prostate lesions on serial magnetic resonance imaging (MRI) examinations in predicting biopsy results. Fifty-five men undergoing two prostate MRI examinations ≥6 months apart, followed by targeted biopsy, were included. Two radiologists assessed dominant lesions for an increase in size or suspicion score. Progression on MRI had lower sensitivity (23.5%-35.3%) and higher specificity (76.2%-90.5%) than prostate-specific antigen (PSA) velocity (sensitivity 70.6%, specificity 52.4%) for predicting positive biopsy. Highest accuracy was achieved by PSA velocity (63.6%) for positive biopsy, and by MRI (65.5%-72.7%) for Gleason >6 tumor. Findings support lesion progression on MRI serving as a basis for performing subsequent targeted biopsy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Estimating glomerular filtration rate (eGFR) has become popular in clinical medicine as an alternative to measured GFR (mGFR), but there are few studies comparing them in clinical practice. We determined mGFR by iohexol clearance in 81 consecutive children in routine practice and calculated eGFR from 14 standard equations using serum creatinine, cystatin C, and urea nitrogen that were collected at the time of the mGFR procedure. Nonparametric Wilcoxon test, Spearman correlation, Bland-Altman analysis, bias (median difference), and accuracy (P15, P30) were used to compare mGFR with eGFR. For the entire study group, the mGFR was 77.9 ± 38.8 mL/min/1.73 m(2). Eight of the 14 estimating equations demonstrated values without a significant difference from the mGFR value and demonstrated a lower bias in Bland-Altman analysis. Three of these 8 equations based on a combination of creatinine and cystatin C (Schwartz et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009;20:629-37; Schwartz et al. Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 2012;82:445-53; Chehade et al. New combined serum creatinine and cystatin C quadratic formula for GFR assessment in children. Clin J Am Soc Nephrol 2014;9:54-63) had the highest accuracy with approximately 60% of P15 and 80% of P30. In 10 patients with a single kidney, 7 with kidney transplant, and 11 additional children with short stature, values of the 3 equations had low bias and no significant difference when compared with mGFR. In conclusion, the 3 equations that used cystatin C, creatinine, and growth parameters performed in a superior manner over univariate equations based on either creatinine or cystatin C and also had good applicability in specific pediatric patients with single kidneys, those with a kidney transplant, and short stature. Thus, we suggest that eGFR calculations in pediatric clinical practice use only a multivariate equation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to describe the clinicopathologic characteristics and oncologic outcomes of patients who underwent nephrectomy for cystic renal masses., Patients and Methods: Using an institutional review board-approved database, we retrospectively reviewed the clinical, pathologic, radiologic, and oncologic outcome data of patients who received nephrectomy for a complex cystic renal mass., Results: Sixty-one patients were identified who received nephrectomy for a complex cystic lesion. Average age was 64 years. Thirty-nine (64%) patients were male. At the time of resection, 1 (1.6%), 3 (4.8%), 53 (86.8%), and 4 (6.5%) had a Bosniak category II, IIF, III, and IV cystic lesion, respectively. Nineteen (31.1%) patients were initially managed expectantly but underwent surgery because of progression of complexity on follow-up. Mean pathologic tumor size was 3.3 cm (range, 0.7-12 cm). Forty-eight (78.6%) of the lesions were found to be malignant. Thirty-seven (77.1%), 5 (10.4%), 4 (8.3%), and 2 (4.1%) were stage T1a, T1b, T2a, and T3a, respectively. Clear cell was the most common histologic subtype (44%), followed by papillary (21.3%), and unclassified RCC (4.9%). With a mean and median follow-up of 48.4 and 43.0 months, respectively, no patients developed a local or metastatic recurrence. All patients were alive at last follow-up., Conclusion: In our series with moderate follow-up, cystic RCCs do not appear to recur or progress regardless of size, histologic subtype, or grade. These findings suggest the malignant potential of cRCCs is significantly less than solid RCCs. Further investigation is required to determine if cRCCs should be classified and managed independently from solid RCCs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: Surfactant protein A (SP-A) plays critical roles in the innate immune system and surfactant homeostasis of the lung. Mutations in SP-A2 of the carbohydrate recognition domain (CRD) impair its glycosylation and are associated with pulmonary fibrosis in humans. We aim to examine how mutations in SP-A that impair its glycosylation affect its biological properties and lead to disease., Main Methods: We generated rat SP-A constructs with two types of mutations that impair its glycosylation: N-glycosylation site mutations (N21T, N207S and N21T/N207S) and disease-associated CRD mutations (G231V, F198S). We transfected these constructs into Chinese hamster ovary (CHO)-K1 cells and assessed biochemical differences in cellular and secreted wild-type and mutant SP-As by western blot, immunofluorescence, and sensitivity to enzymatic digestion., Key Findings: Mutations of the CRD completely impaired SP-A secretion, whereas mutations of N-glycosylation sites had little effect. Both types of mutations formed nonidet p-40 (NP-40) insoluble aggregates, but the aggregates only from CRD mutations could be partially rescued by a chemical chaperone, 4-phenylbutyrate acid (4-PBA). The majority of CRD mutant SP-A was retained in the endoplasmic reticulum. Moreover, both types of mutations reduced SP-A stability, with CRD mutant SP-A being more sensitive to chymotrypsin digestion. Both types of soluble mutant SP-A could be degraded by the proteasome pathway, while insoluble aggregates could be additionally degraded by the lysosomal pathway., Significance: Our data provide evidence that the differential glycosylation of SP-A may play distinct roles in SP-A secretion, aggregation and degradation which may contribute to familial pulmonary fibrosis caused by SP-A2 mutations., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Inorganic-framework molecularly imprinted TiO2/SiO2 nanocomposite (MIP-TiO2/SiO2) was successfully prepared by sol-hydrothermal method using 4-nitrophenol as template. The morphology, structure, optical property, zeta-potential and photocurrent of MIP-TiO2/SiO2 were characterized. The adsorption performance and photocatalytic selectivity were also studied. MIP-TiO2/SiO2 shows higher adsorption capacity and selectivity than the non-imprinted TiO2/SiO2 (NIP-TiO2/SiO2). Kinetics results show that the adsorption equilibrium of 4-nitrophenol on MIP-TiO2/SiO2 is established within 20 min, and the adsorption process obeys the pseudo-second-order model. Moreover, MIP-TiO2/SiO2 can completely degrade 4-nitrophenol within 30 min, while NIP-TiO2/SiO2 takes 110 min. It was found that the MIP-TiO2/SiO2 photocatalyst shows molecular recognition ability, leading to selective adsorption and molecular recognitive photocatalytic degradation of 4-nitrophenol. Furthermore, because of its inorganic framework, MIP-TiO2/SiO2 shows excellent reusability., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Heart failure (HF) is approaching an epidemic proportion and has become one of the leading causes of death. It imposes a great burden on the healthcare system and society. Remodeling of cardiomyocyte membranes has a profound role in the pathogenesis of HF. However, whether dynamin (DNM), a membrane-remodeling GTPase, is associated with HF remains unclear., Methods and Results: Here, we identified that DNM2 is necessary for the maintenance of cardiac function. Endogenous DNM2 protein levels were gradually decreased in parallel with the progression of HF in different experimental animal models. Decreased DNM2 level was also observed in the end-stage failing human heart. DNM2-deficient zebrafish exhibited signs of notable cardiac apoptosis and eventually developed severe HF. Mechanistic study showed that DNM2 downregulation caused cardiomyocyte sarcoplasmic reticulum Ca(2+) overload and subsequent mitochondria-dependent apoptosis. These events were preceded by enhanced membrane translocation of the L-type Ca(2+) channel due to DNM2 deficiency-mediated membrane trafficking dysfunction. Furthermore, prevention of cardiomyocyte Ca(2+)-mishandling largely ameliorated the DNM2 deficiency-associated cardiomyocyte apoptosis and HF., Conclusions: DNM2 mediates HF by modulating Ca(2+)-dependent apoptotic death of cardiomyocyte. The finding may shed light on the new strategy of HF treatment., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Hair follicles periodically undergo regeneration. The balance between activators and inhibitors may determine the time required for telogen hair follicles to reenter anagen. We previously reported that Wnt10b (wingless-type mouse mammary tumor virus integration site family member 10b) could promote the growth of hair follicles in vitro. To unveil the roles of Wnt10b in hair follicle regeneration, we established an in vivo mouse model using intradermal injection. On the basis of this model, we found that Wnt10b could induce the biological switch of hair follicles from telogen to anagen when overexpressed in the skin. The induced hair follicles expressed structure markers and could cycle normally into catagen. Conversely, anagen onset was abrogated by the knockdown of Wnt10b with small interfering RNA (siRNA). The Wnt10b aberrant expression data suggest that it is one of the activators of hair follicle regeneration. The β-catenin protein is translocated to the nucleus in Wnt10b-induced hair follicles. The biological effects of Wnt10b were abrogated when β-catenin expression was downregulated with siRNA. These data revealed that Wnt10b might induce hair follicle regeneration in vivo via the enhanced activation of the canonical Wnt signaling pathway. To our knowledge, our data provide previously unreported insights into the regulation of hair follicle cycling and provide potential therapeutic targets for hair follicle-related diseases.

Although the importance of Wnt3a in melanocyte development has been well recognized, the effect of Wnt3a in normal HF melanocytes has not been clearly elucidated yet. Thus, we sought to examine the presence and location of Wnt3a in HF during hair cycle. By using melanocyte-targeted Dct-LacZ transgenic mice, we found that Wnt3a signaling is activated in mouse HF melanocytes during anagen of hair cycle. To further explore the potential functions of Wnt3a in mouse melanocytes, we infected melan-a cells with AdWnt3a to serve as the production source of Wnt3a protein. We demonstrated that Wnt3a promoted melanogenesis through upregulation of MITF and its downstream genes, tyrosinase and TRP1, in melanocytes. In vivo, AdWnt3a rescued the effects of AdsimMITF on HF melanocytes and promoted melanin synthesis. Our results suggest that Wnt3a plays an important role in mouse HF melanocytes homeostasis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We report a soft tissue sarcoma from the thigh with morphologic features resembling Ewing sarcoma, clear cell sarcoma, and myoepithelial tumor of soft tissue. In addition, the genetic and immunohistochemical findings do not correspond to any established pattern, so the tumor does not clearly fit into any one classification. The karyotype analysis revealed a rare chromosomal rearrangement, t(6;22)(p22;q12), that previously has been reported in bone and epithelial tumors. Molecular studies confirmed the presence of an EWSR1-POU5F1 fusion creating a chimeric gene with the N-terminal transcriptional activation domain of EWSR1 and the C-terminal POU DNA binding domain of POU5F1. This report is novel in that to our knowledge, it is the first complete molecular characterization of an EWSR1-POU5F1 fusion in a soft tissue sarcoma. Evaluation of existing data on the known EWSR1-POU5F1 tumors suggests that the fusion gene functions in a wide variety of cell types and may modify the differentiation state of cells, resulting in susceptibility to tumorigenesis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Urothelial umbrella cells are characterized by apical, rigid membrane plaques, which contain four major uroplakin proteins (UP Ia, Ib, II and III) forming UPIa/UPII and UPIb/UPIII pairs. These integral membrane proteins are thought to play an important role in maintaining the physical integrity and the permeability barrier function of the urothelium. We asked whether the four uroplakins always coexpress in the entire human lower urinary tract. We stained immunohistochemically (ABC-peroxidase method) paraffin sections of normal human ureter (n = 18) and urinary bladder (n = 10) using rabbit antibodies against UPIa, UPIb, UPII and UPIII; a recently raised mouse monoclonal antibody (MAb), AU1, and two new MAbs, AU2 and AU3, all against UPIII; and mouse MAbs against umbrella cell-associated cytokeratins CK18 and CK20. Immunoblotting showed that AU1, AU2 and AU3 antibodies all recognized the N-terminal extracellular domain of bovine UPIII. By immunohistochemistry, we found that in 15/18 cases of human ureter, but in only 2/10 cases of bladder, groups of normal-looking, CK18-positive umbrella cells lacked both UPIII and UPIb immunostaining. The UPIb/UPIII-negative cells showed either normal or reduced amounts of UPIa and UPII staining. These data were confirmed by double immunofluorescence microscopy. The distribution of the UPIb/UPIII-negative umbrella cells was not correlated with localized urothelial proliferation (Ki-67 staining) or with the distribution pattern of CK20. Similar heterogeneities were observed in bovine but not in mouse ureter. We provide the first evidence that urothelial umbrella cells are heterogeneous as some normal-looking umbrella cells can possess only one, instead of two, uroplakin pairs. This heterogeneity seems more prominent in the urothelium of human ureter than that of bladder. This finding may indicate that ureter urothelium is intrinsically different from bladder urothelium. Alternatively, a single lineage of urothelium may exhibit different phenotypes resulting from extrinsic modulations due to distinct mesenchymal influence and different degrees of pressure and stretch in bladder versus ureter. Additional studies are needed to distinguish these two possibilities and to elucidate the physiological and pathological significance of the observed urothelial and uroplakin heterogeneity.

Background: Primary vesicoureteral reflux (VUR) is a hereditary disorder characterized by the retrograde flow of urine into the ureters and kidneys. It affects about 1% of the young children and is thus one of the most common hereditary diseases. Its associated nephropathy is an important cause of end-stage renal failure in children and adults. Recent studies indicate that genetic ablation of mouse uroplakin (UP) III gene, which encodes a 47 kD urothelial-specific integral membrane protein forming urothelial plaques, causes VUR and hydronephrosis., Methods: To begin to determine whether mutations in UP genes might play a role in human VUR, we genotyped all four UP genes in 76 patients with radiologically proven primary VUR by polymerase chain reaction (PCR) amplification and sequencing of all their exons plus 50 to 150 bp of flanking intronic sequences., Results: Eighteen single nucleotide polymorphisms (SNPs) were identified, seven of which were missense, with no truncation or frame shift mutations. Since healthy relatives of the VUR probands are not reliable negative controls for VUR, we used a population of 90 race-matched, healthy individuals, unrelated to the VUR patients, as controls to perform an association study. Most of the SNPs were not found to be significantly associated with VUR. However, SNP1 of UP Ia gene affecting a C to T conversion and an Ala7Val change, and SNP7 of UP III affecting a C to G conversion and a Pro154Ala change, were marginally associated with VUR (both P= 0.08). Studies of additional cases yielded a second set of data that, in combination with the first set, confirmed a weak association of UP III SNP7 in VUR (P= 0.036 adjusted for both subsets of cases vs. controls)., Conclusion: Such a weak association and the lack of families with simple dominant Mendelian inheritance suggest that missense changes of uroplakin genes cannot play a dominant role in causing VUR in humans, although they may be weak risk factors contributing to a complex polygenic disease. The fact that no truncation or frame shift mutations have been found in any of the VUR patients, coupled with our recent finding that some breeding pairs of UP III knockout mice yield litters that show not only VUR, but also severe hydronephrosis and neonatal death, raises the possibility that major uroplakin mutations could be embryonically or postnatally lethal in humans.

Human tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated Kunitz-type serine proteinase inhibitor that is secreted by all cells of the vasculature, and presumably plays a role in the regulation of plasmin-mediated matrix remodeling. In this report, we describe the cloning and expression of a full-length cDNA for bovine TFPI-2 that exhibits 72% sequence identity with that of human TFPI-2. Following a 22 residue signal peptide, the mature protein contains 212 amino acids with 18 cysteines, three putative N-glycosylation sites, and one putative O-glycosylation site. The deduced sequence of mature bovine TFPI-2 revealed a short acidic amino-terminal region, three tandem Kunitz-type domains, and a carboxy-terminal tail highly enriched in basic amino acids. Recombinant bovine TFPI-2 was expressed in HEK 293 cells and resolved into two isoforms, designated as alpha-TFPI-2 (M(r) 33 kDa) and beta-TFPI-2 (M(r) 31 kDa), which presumably represent differentially glycosylated forms of the inhibitor. Similar to human TFPI-2, both bovine TFPI-2 isoforms exhibited strong inhibitory activity towards trypsin and plasmin, and weak inhibitory activity towards the factor VIIa-tissue factor complex.