Characterization of Metabolic Patterns in Mouse Oocytes during Meiotic Maturation.

Well-balanced and timed metabolism is essential for making a high-quality egg. However, the metabolic framework that supports oocyte development remains poorly understood. Here, we obtained the temporal metabolome profiles of mouse oocytes during in vivo maturation by isolating large number of cells at key stages. In parallel, quantitative proteomic analyses were conducted to bolster the metabolomic data, synergistically depicting the global metabolic patterns in oocytes. In particular, we discovered the metabolic features during meiotic maturation, such as the fall in polyunsaturated fatty acids (PUFAs) level and the active serine-glycine-one-carbon (SGOC) pathway. Using functional approaches, we further identified the key targets mediating the action of PUFA arachidonic acid (ARA) on meiotic maturation and demonstrated the control of epigenetic marks in maturing oocytes by SGOC network. Our data serve as a broad resource on the dynamics occurring in metabolome and proteome during oocyte maturation.

Benchmarking of computational methods for predicting circRNA-disease associations.

Accumulating evidences demonstrate that circular RNA (circRNA) plays an important role in human diseases. Identification of circRNA-disease associations can help for the diagnosis of human diseases, while the traditional method based on biological experiments is time-consuming. In order to address the limitation, a series of computational methods have been proposed in recent years. However, few works have summarized these methods or compared the performance of them. In this paper, we divided the existing methods into three categories: information propagation, traditional machine learning and deep learning. Then, the baseline methods in each category are introduced in detail. Further, 5 different datasets are collected, and 14 representative methods of each category are selected and compared in the 5-fold, 10-fold cross-validation and the de novo experiment. In order to further evaluate the effectiveness of these methods, six common cancers are selected to compare the number of correctly identified circRNA-disease associations in the top-10, top-20, top-50, top-100 and top-200. In addition, according to the results, the observation about the robustness and the character of these methods are concluded. Finally, the future directions and challenges are discussed.

Antibiotic resistance and virulence genes in Helicobacter pylori strains isolated from children in Shanghai, China (2019-2022).

BACKGROUND: The increasing prevalence of antibiotic-resistant Helicobacter pylori strains poses a significant threat to children's health. This study investigated antibiotic resistance rates in Helicobacter pylori strains isolated from children in Shanghai and analyzed the presence of virulence genes in these strains. METHODS: We obtained 201 Helicobacter pylori strains from pediatric patients with upper gastrointestinal symptoms who underwent gastrointestinal endoscopy between 2019 and 2022. Subsequently, we performed antibiotic susceptibility tests and virulence gene PCR assays on these strains. RESULTS: Helicobacter pylori resistance rates of 45.8%, 15.4%, 1.0%, and 2.5% were detected for metronidazole, clarithromycin, amoxicillin, and levofloxacin, respectively. Among all isolates, 64.7% exhibited resistance to at least one antibiotic. Resistance to metronidazole and clarithromycin increased from 2019 to 2022. The predominant vacA gene subtype was vacA s1a/m2. The prevalence of vacA m2 and dupA exhibited an upward trend, while oipA presented a decreasing trend from 2019 to 2022. The prevalence of dupA was significantly higher in gastritis than peptic ulcer disease, and in non-treatment compared to treatment groups. CONCLUSIONS: Helicobacter pylori antibiotic resistance remains high in children and has risen in recent years. Therefore, the increasing use of metronidazole and clarithromycin requires increased monitoring in children. No association was observed between antibiotic resistance and virulence gene phenotypes.

The clinical outcome of emergency superficial temporal artery-to-middle cerebral artery bypass in acute ischemic stroke with large vessel occlusion.

The role of superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass in acute ischemic stroke (AIS) is contentious, with no evidence in patients with AIS and large vessel occlusion (AIS-LVO). We conducted a cohort study to assess emergency STA-MCA outcomes in AIS-LVO and a meta-analysis to evaluate STA-MCA outcomes in early AIS treatment. From January 2018 to March 2021, we consecutively recruited newly diagnosed AIS-LVO patients, dividing them into STA-MCA and non-STA-MCA groups. To evaluate the neurological status and outcomes, we employed the National Institutes of Health Stroke Scale (NIHSS) during the acute phase and the modified Rankin Scale (mRS) during the follow-up period. Additionally, we conducted a meta-analysis encompassing all available clinical studies to assess the impact of STA-MCA on patients with AIS. In the cohort study (56 patients), we observed more significant neurological improvement in the STA-MCA group at two weeks (p = 0.030). However, there was no difference in the clinical outcomes between the two groups. Multivariable logistic regression identified the NIHSS at two weeks (OR: 0.840; 95% CI: 0.754-0.936, p = 0.002) as the most critical predictor of a good outcome. Our meta-analysis of seven studies indicated a 67% rate for achieving a good outcome (mRS < 3) at follow-up points (95% CI: 57%-77%, I2 = 44.1%). In summary, while the meta-analysis suggested the potential role of STA-MCA bypass in mild to moderate AIS, our single-center cohort study indicated that STA-MCA bypass does not seem to improve the prognosis of patients who suffer from AIS-LVO.

A dissipative particle dynamics simulation of controlled loading and responsive release of theranostic agents from reversible crosslinked triblock copolymer vesicles.

To control the transport stability and release efficiency of loaded theranostic drugs in triblock copolymer carriers, the reversible crosslinking ability is of great significance. A molecular level exploration of such a function is needed to extend existing stabilizing and responsive dissociation mechanisms of carriers. Here, dissipative particle dynamics simulations were used to first demonstrate the formation of triblock copolymer vesicular carriers. Chemical crosslinking was used to strengthen the structural stability of the vesicle shell to avoid drug leakage. Reversible decrosslinking along with dissociation of the vesicle and release of loaded drugs were then explored. The structural, energetic and dynamical properties of the system were discussed at the molecular level. The regulation mechanism of drug release patterns was revealed by systematically exploring the effect of intra and intermolecular repulsive interactions. The results indicate that the chemical crosslinking of copolymers enhanced the compactness of the vesicle shell with a strengthened microstructure, increased binding energy, and limited chain migration, thus achieving more stable delivery of drugs. In terms of drug release, we clarified how the pairwise interactions of beads in the solution system affect the responsive dissociation of the vesicle and associated release patterns (speed and amount) of drugs. More efficient delivery and smart release of theranostic drugs are achieved using such reversible crosslinked triblock copolymer vesicles.

Association of ultra-processed foods consumption with risk of cardio-cerebrovascular disease: A systematic review and meta-analysis of cohort studies.

AIMS: The epidemiological evidence regarding the impact of ultra-processed foods (UPFs) on the risk of cardio-cerebrovascular diseases (CCVDs) is controversial. The aim of this systematic review and meta-analysis is to examine the association between UPF consumption and the risk of CCVDs within cohort studies. DATA SYNTHESIS: A systematic literature search was conducted across multiple databases, including PubMed/Medline, Embase, Web of Science, Scopus, and the Cochrane Library databases, covering the inception of these databases up until January 1st, 2023. A total of 39 cohort studies involving 63,573,312 human participants were deemed eligible according to the inclusion criteria. Utilizing random-effects models, risk ratios (RRs) were estimated to determine the pooled results. Our findings indicate a significant association between a higher consumption of UPF and an increased likelihood of CCVDs (RR: 1.08, 95% CI: 1.01-1.16, I2 = 89%; p < 0.01) compared to individuals who either abstain from or consume lesser amounts of UPF. Nonlinear dose-response meta-analyses showed that a consistent high intake of UPFs was associated with an elevated risk of developing CCVDs (p non-linearity <0.001). Notably, the risk of CCVDs escalated by approximately 7% with an UPF intake of up to 1 serving per day. Subgroup analysis further revealed a significant augmentation in the risk of total CVD and hypertension with increased UPF consumption. CONCLUSIONS: A higher intake of UPF significantly increases the risk of developing CCVDs. Prospective studies controlling for confounding factors are needed to validate the relationship between UPF intake and the development of CCVDs.

Prevalence, in-hospital mortality, and factors related to neurogenic pulmonary edema after spontaneous subarachnoid hemorrhage: a systematic review and meta-analysis.

Neurogenic pulmonary edema (NPE) is a life-threatening and severe complication in patients with spontaneous subarachnoid hemorrhage (SAH). The prevalence of NPE varies significantly across studies due to differences in case definitions, study populations, and methodologies. Therefore, a precise estimation of the prevalence and risk factors related to NPE in patients with spontaneous SAH is important for clinical decision-makers, policy providers, and researchers. We conducted a systematic search of the PubMed/Medline, Embase, Web of Science, Scopus, and Cochrane Library databases from their inception to January 2023. Thirteen studies were included in the meta-analysis, with a total of 3,429 SAH patients. The pooled global prevalence of NPE was estimated to be 13%. Out of the eight studies (n = 1095, 56%) that reported the number of in-hospital mortalities of NPE among patients with SAH, the pooled proportion of in-hospital deaths was 47%. Risk factors associated with NPE after spontaneous SAH included female gender, WFNS class, APACHE II score ≥ 20, IL-6 > 40 pg/mL, Hunt and Hess grade ≥ 3, elevated troponin I, elevated white blood cell count, and electrocardiographic abnormalities. Multiple studies showed a strong positive correlation between the WFNS class and NPE. In conclusion, NPE has a moderate prevalence but a high in-hospital mortality rate in patients with SAH. We identified multiple risk factors that can help identify high-risk groups of NPE in individuals with SAH. Early prediction of the onset of NPE is crucial for timely prevention and early intervention.

Classification and Gene Structure of Aquaporins.

Aquaporins (AQPs) are a family of membrane water channels that basically function as regulators of intracellular and intercellular water flow. To date, 13 AQPs, distributed widely in specific cell types in various organs and tissues, have been characterized in humans. A pair of NPA boxes forming a pore is highly conserved among all aquaporins and is also key residues for the classification of AQP superfamily into four groups according to primary sequences. AQPs may also be classified based on their transport properties. So far, chromosome localization and gene structure of 13 human AQPs have been identified, which is definitely helpful for studying phenotypes and potential targets in naturally occurring and synthetic mutations in human or cells.

Protein Structure and Modification of Aquaporins.

Aquaporins (AQPs) allow water molecules and other small, neutral solutes to quickly pass through membrane. The protein structures of AQPs solved by crystallographic methods or cryo-electron microscopy technology show that AQP monomer consists of six membrane-spanning alpha-helices that form the central water-transporting pore. AQP monomers assemble to form tetramers, forming the functional units in the membrane, to transport water or other small molecules. The biological functions of AQPs are regulated by posttranslational modifications, e.g., phosphorylation, ubiquitination, glycosylation, subcellular distribution, degradation and protein interactions. Modifications of AQP combined with structural properties contribute to a better functional mechanism of AQPs. Insight into the molecular mechanisms responsible for AQP modifications as well as gating and transport properties proved to be fundamental to the development of new therapeutic targets or reliable diagnostic and prognostic biomarkers.

Expression Regulation and Trafficking of Aquaporins.

Aquaporins (AQPs) mediate the bidirectional water flow driven by an osmotic gradient. Either gating or trafficking allows for rapid and specific AQP regulation in a tissue-dependent manner. The regulatory mechanisms of AQP2 are discussed mainly in this chapter, as the mechanisms controlling the regulation and trafficking of AQP2 have been very well studied. The targeting of AQP2 to the apical plasma membrane of collecting duct principal cells is mainly regulated by the action of arginine vasopressin (AVP) on the type 2 AVP receptor (V2R), which cause increased intracellular cAMP or elevated intracellular calcium levels. Activation of these intracellular signaling pathways results in vesicles bearing AQP2 transport, docking and fusion with the apical membrane, which increase density of AQP2 on the membrane. The removal of AQP2 from the membrane requires dynamic cytoskeletal remodeling. AQP2 is degraded through the ubiquitin proteasome pathway and lysosomal proteolysis pathway. Finally, we review updated findings in transcriptional and epigenetic regulation of AQP2.

Optimal treatment options for uterine submucosal fibroids: Percutaneous microwave ablation versus transcervical resection of myoma.

OBJECTIVES: To compare the efficacy and safety of percutaneous microwave ablation (PMWA) and transcervical resection of myoma (TCRM) for submucosal fibroids. METHODS: From January 2019 to January 2021, we conducted a randomized controlled study involving patients with symptomatic uterine submucosal fibroids. Questionnaires were also used to measure the uterine fibroid symptom (UFS) scores and quality of life (QoL) scores before and after treatment at 3, 6, and 12 months. Outcomes, adverse events, hemoglobin recovery, and submucosal fibroid volume of both groups were also compared. Operation time, amount of bleeding, hospital stay time, and occurrence of complications were compared in groups with fibroids of different lengths. RESULTS: Follow-up after surgery showed that UFS scores at 3, 6, and 12 months were significantly lower in each group, while QoL scores increased significantly. For fibroids less than 3 cm, surgical time was 34.2 ± 9.9 min, incidence of perioperative complications was 4.2%, and both decreased significantly, compared to the surgical time of the PMWA group (40.0 ± 8.1 min) and incidence of perioperative complications (24%; p < .05 for both). For uterine submucosal fibroids >5 cm, the operation time in the PMWA group was 92.7 ± 16.0 min, intraoperative bleeding volume was 22.7 ± 6.4 mL, and hospital stay was 2.7 ± 1.1 days, which were significantly less than the procedural time (107 ± 11.9 min), intraoperative bleeding loss (45.9 ± 12.8 mL), and length of hospital stay (5.0 ± 1.1 days) in the TCRM group. The differences were statistically significant (p < .05). CONCLUSIONS: PMWA and TCRM were both effective treatments for uterine submucosal fibroids. For fibroids shorter than 3 cm in length, especially pedicled submucosal fibroids, TCRM has absolute advantages; however, for uterine submucosal fibroids >5 cm, PMWA avoids perioperative complications, such as uterine perforation, water poisoning syndrome, and the need for repeat surgery, and is considered the preferred mode of treatment. Therefore, personalized treatment should be used for different patients with uterine submucosal fibroids.

[Progress in stimuli-responsive molecularly imprinted polymers for enrichment analysis of trace components in traditional Chinese medicine].

Molecularly imprinted polymers demonstrate outstanding performance in the research on trace ingredients because of their high selectivity. Stimuli-responsive molecularly imprinted polymers(STR-MIPs) with the introduction of different responsive groups on the basis of traditionally imprinted materials can undergo reversible transformations when exposed to external stimuli such as temperature, magnetism, pH or light. Such responsiveness, combined with the specific recognition, endows STR-MIPs with excellent perfor-mance in trace component studies. Traditional Chinese medicine(TCM) contains complex components with trace content, and thus STR-MIPs have broad application prospects in the enrichment analysis of trace components in TCM. This paper elaborates on the application of STR-MIPs in the enrichment analysis of trace components in TCM from the perspectives of different stimuli, summarized relevant research achievements in the recent five years to broaden the application fields of molecular imprinting, and proposed a few opi-nions about their future development.

Elevated lncRNA-UCA1 upregulates EZH2 to promote inflammatory response in sepsis-induced pneumonia via inhibiting HOXA1.

Sepsis is characterized by a dysregulated inflammatory response. We aimed to explore the role of the long noncoding RNA urothelial carcinoma associated 1 (lncRNA UCA1)/enhancer of zeste homolog 2 (EZH2)/homeobox A1 (HOXA1) axis in sepsis-induced pneumonia. The sepsis rat models and RLE-6TN cellular sepsis-induced pneumonia models were established using ligation and puncture (CLP) and lipopolysaccharide (LPS). The expression of UCA1, EZH2, and HOXA1 in rat lung tissues and RLE-6TN cells was detected. Then, the CLP rats were respectively treated with lentivirus to upregulate or downregulate the expression of UCA1 and EZH2 to measure their roles in the pathology, apoptosis, inflammation and phosphorylated NF-κB p65(p-p65) levels in CLP rat lung tissues. UCA1 and EZH2 expression was upregulated or downregulated in LPS-induced RLE-6TN cells to explore their effects on cell viability, apoptosis, inflammation and p-p65 levels. The interactions among UCA1, EZH2, and HOXA1 were identified. UCA1 and EZH2 were upregulated whereas HOXA1 was downregulated in CLP rat lung tissues and LPS-induced RLE-6TN cells. Elevated UCA1 or increased EZH2 aggravated pathology and promoted apoptosis, inflammation and phosphorylated NF-κB p-65 levels in CLP rat lung tissues, and inhibited viability while facilitated apoptosis, inflammation and phosphorylated NF-κB p-65 levels in LPS-induced RLE-6TN cells. Silenced EZH2 reversed the effects of UCA1 elevation on sepsis-induced pneumonia. UCA1 suppressed HOXA1 expression through physically interacting with EZH2. UCA1 overexpression upregulates EZH2 to repress HOXA1 expression, thus aggravating the progression of sepsis-induced pneumonia, which could be alleviated by EZH2 inhibition.

Association of MTOR and PDGFRA gene polymorphisms with different degrees of myopia severity.

This study aims to investigate the associations of SNPs in the mammalian target of rapamycin (MTOR) and the platelet derived growth factor receptor alpha (PDGFRA) genes with different degrees of myopia severity in Han and Zhuang populations. The SNPs of MTOR (rs1057079, rs1064261, and rs2536) and PDGFRA (rs1800812, rs35597368, rs4358459, rs6554162, and rs7677751) were analyzed among 1347 patients with myopia (849 patients with high myopia and 498 patients with mild to moderate myopia) and 453 controls without myopia in Guangxi, China (collected 2016-2018). Genetic model association analysis was performed on each SNP in different myopia subgroups. The associations of rs1057079 and rs1064261 with mild to moderate myopia were observed under the dominant models (rs1057079: OR = 1.324, 95%CI: 1.005-1.744, P = 0.046; rs1064261: OR = 1.597, 95%CI: 1.099-2.319, P = 0.014). However, the association of SNP rs1057079 could not withstand multiple correction. The number of adverse genotypes in each sample was counted. Results showed that in the high myopia group, the levels of risk of myopia in patients carrying three to four and five to eight adverse genotypes were 1.734 and 2.062 times the level of risk in patients carrying two or lower genotypes, respectively. After the stratified analyses of Han and Zhuang populations, the Zhuang populations consistently had high frequencies of myopia. This study provides evidence suggesting that the MTOR and PDGFRA genes are associated with different degrees of myopia severity and have gene-gene interactions. In addition, this study discovered a new SNP of MTOR (rs1064261) that is associated with myopia. Thus, further longitudinal studies are warranted.

GSK-3ß inhibitor TDZD-8 prevents reduction of aquaporin-1 expression via activating autophagy under renal ischemia reperfusion injury.

Renal ischemia/reperfusion (I/R) injury is a main cause of acute kidney injury (AKI). Aquaporin (AQP)-1 water channel in the kidney is critical for the maintenance of water homeostasis and the urinary concentrating ability. Increasing evidence supports an important role of autophagy in the pathogenesis of AKI induced by renal I/R. The purpose of the present study is to investigate whether activation of autophagy prevents downregulation of AQP1 protein induced by renal I/R and potential molecular mechanisms. Renal I/R induced consistently reduced protein expression of AQP1, 2, and 3, as well as sodium cotransporters Na+ -K+ -2Cl- cotransporter and α-Na,K-ATPase, which was associated with increased urine output and decreased creatinine clearance in rats. Renal I/R also suppressed autophagy and increased inflammatory responses in the kidney. 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), the glycogen synthase kinase-3ß inhibitor, ameliorated renal injury under I/R, activated autophagy and markedly increased expression of AQPs and sodium transporters in the kidney, which was associated with improved urine output and creatinine clearance in rats. Hypoxia/reoxygenation (H/R) induced suppression of autophagy and downregulation of AQP1 in murine inner medullary collecting duct 3 (IMCD3) cells, which was fully prevented by TDZD-8 treatment. Inhibition of autophagy by 3-methyladenine or Atg5 gene knockdown attenuated recovery of AQP1 protein expression induced by TDZD-8 in IMCD3 cells with H/R. Interleukin-1 beta (IL-1ß) decreased the abundance of AQP1 protein in IMCD3 cells. H/R induced increases in protein expression of nod-like receptor pyrin domain-containing 3 and IL-1ß, which was reversed by TDZD-8. In conclusion, TDZD-8 treatment prevented downregulation of AQP1 expression under renal I/R injury, likely via activating autophagy and decreasing IL-1ß production.

Designing polymersomes with inhomogeneous membranes by co-assembly of block copolymers for controlled morphological reversibility.

Polymersomes with inhomogeneous membranes in composition and structure have generated widespread interest for the preparation of functionalized nanocarriers. We propose a simple but versatile strategy to manipulate inhomogeneous subdomains on polymersome membranes by the co-assembly of block copolymer blends with varied molecular architectures and chemistries. Both binary and ternary copolymer blends are considered to construct polymersomes, and the subdomains of the membranes are formed by controlling the difference in the flexibility and rigidity of different blocks. This difference contributes to the formation of disk-like domains (by rigid blocks) and soft domains (by flexible blocks) on the membrane. An interesting effect of this structure is that in response to external stimuli, the soft membrane domain becomes worm-like or porous to "open" the polymersome for matter exchange, while the rigid domain stays undecomposed and acts like an anchor binding all flexible copolymers. Once the external stimuli disappear, all flexible copolymers can be pulled back to restore the original polymersome morphology (i.e., "close" the polymersome). The specific morphological reversibility of hybrid polymersomes holds great potential for practical applications where changeable membrane permeability or shape under environmental stimuli is highly needed.

CircRNA/miRNA/mRNA axis participates in the progression of partial bladder outlet obstruction.

BACKGROUND: More and more evidence showed that circRNA/miRNA/mRNA axis played a vital role in the pathogenesis of some diseases. However, the role of circRNA/miRNA/mRNA axis in partial bladder outlet obstruction (pBOO) remains unknown. Our study aimed to explore the complex regulatory mechanism of circRNA/miRNA/mRNA axis in pBOO. METHODS: The pBOO rat model was established, and the bladder tissues were collected for mRNA sequencing. The differentially expressed mRNAs were analyzed by high-throughput sequencing, and the GO and KEGG analysis of the differentially expressed mRNAs were performed. Competing endogenous RNAs (ceRNAs) analysis identified the potential regulation function of circRNA/miRNA/mRNA axis in pBOO. qRT-PCR detected the expression of circRNA/miRNA/mRNA. miRanda software was performed to predict the relationship between circRNA and miRNA, miRNA and mRNA. RESULTS: Compared with the sham group, a total of 571 mRNAs were differentially expressed in the pBOO group, of which 286 were up-regulated and 285 were down-regulated. GO analysis showed that the mRNAs were mainly involved in cellular process, single-organism process, and cell, etc. KEGG analysis showed that the enriched signaling pathways were metabolic pathways, cell adhesion molecules (CAMs), and HTLV-I infection, etc. Based on the previous transcriptome data and differentially expressed circRNAs, we drew the ceRNA network regulation diagram. qRT-PCR results confirmed that chr3:113195876|113197193/rno-miR-30c-1-3p/Gata4, chr1:126188351|126195625/rno-miR-153-5p/Diaph3, and chr9:81258380|81275269/rno-miR-135b-5p/Pigr axis may have ceRNA function. miRanda confirmed there have the binding sites of circRNA/miRNA/mRNA axis. CONCLUSIONS: CircRNA/miRNA/mRNA axis was involved in the progression of pBOO. Our research on the circRNA/miRNA/mRNA axis revealed new pathogenesis and treatment strategies for pBOO.

Statins attenuate cholesterol-induced ROS via inhibiting NOX2/NOX4 and mitochondrial pathway in collecting ducts of the kidney.

BACKGROUND: Statins therapy has been primarily recommended for the prevention of cardiovascular risk in patients with chronic kidney diseases. Statins has also been proved some benefits in lipid-induced kidney diseases. The current study aims to investigate the protection and underlying mechanisms of statins on renal tubular injuries induced by cholesterol overloaded. METHODS: We used tubular suspensions of inner medullary collecting duct (IMCD) cells from rat kidneys and mouse collecting duct cell line mpkCCD cells to investigate the effect of statins on reactive oxygen species (ROS) production induced by cholesterol. Protein and mRNA expression of NADPH oxidase 2 (NOX2) /NOX4 was examined by Western blot and RT-PCR in vitro studies and in rats with 5/6 nephrectomy and high-fat diet. Mitochondrial morphology and membrane potential was observed by Mito-tracker and JC-1. RESULTS: Statins treatment was associated with decreased NOX2 and NOX4 protein expression and mRNA levels in 5/6Nx rats with high-fat diet. Statins treatment markedly reduced the ROS production in IMCD suspensions and mpkCCD cells. Also, statins reduced NOX2 and NOX4 protein expression and mRNA levels in cholesterol overload mpkCCD cells and improved mitochondrial morphology and function. CONCLUSION: Statins prevented ROS production induced by cholesterol in the kidney, likely through inhibiting NOXs protein expression and improving mitochondrial function. Statins may be a therapeutic option in treating obesity-associated kidney diseases.

A Novel Airborne Molecular Contaminants Sensor Based on Sagnac Microfiber Structure.

The impact of airborne molecular contaminants (AMCs) on the lifetime of fused silica UV optics in high power lasers (HPLs) is a critical issue. In this work, we demonstrated the on-line monitoring method of AMCs concentration based on the Sagnac microfiber structure. In the experiment, a Sagnac microfiber loop with mesoporous silica coating was fabricated by the microheater brushing technique and dip coating. The physical absorption of AMCs in the mesoporous coating results in modification of the surrounding refractive index (RI). By monitoring the spectral shift in the wavelength domain, the proposed structure can operate as an AMCs concentration sensor. The sensitivity of the AMCs sensor can achieve 0.11 nm (mg/m3). By evaluating the gas discharge characteristic of four different low volatilization greases in a coarse vacuum environment, we demonstrated the feasibility of the proposed sensors. The use of these sensors was shown to be very promising for meeting the requirements of detecting trace amounts of contaminants.

Activation of TGR5 restores AQP2 expression via the HIF pathway in renal ischemia-reperfusion injury.

Renal ischemia-reperfusion (I/R) injury is associated with markedly reduced protein expression of aquaporins (AQPs). Membrane G protein-coupled bile acid receptor-1 (TGR5) has shown protective roles in some kidney diseases. The purpose of the current study was to investigate whether activation of TGR5 prevented the decreased protein expression of AQPs in rodents with renal I/R injury and potential mechanisms. TGR5 agonist lithocholic acid (LCA) treatment reduced polyuria after renal I/R injury in rats. LCA prevented the decreased abundance of AQP2 protein and upregulated hypoxia-inducible factor (HIF)-1α protein expression, which were associated with decreased protein abundance of NF-κB p65 and IL-1ß. After renal I/R, mice with tgr5 gene deficiency exhibited further decreases in AQP2 and HIF-1α protein abundance and increases of IL-1ß and NF-κB p65 protein expression compared with wild-type mice. In primary cultured inner medullary collecting duct cells with hypoxia/reoxygenation, LCA induced markedly increased protein expression of AQP2 and HIF-1α, which were partially prevented by the PKA inhibitor H89. FG4592, a prolyl-4-hydroxylase domain-containing protein inhibitor, increased HIF-1α and AQP2 protein abundance in association with decreased NF-κB p65 protein expression in inner medullary collecting duct cells with hypoxia/reoxygenation. In conclusion, TGR5 stimulation by LCA prevented downregulation of renal AQPs in kidney with I/R injury, likely through activating HIF-1α signaling and suppressing inflammatory responses.NEW & NOTEWORTHY Stimulation of the membrane G protein-coupled bile acid receptor TGR5 by lithocholic acid (LCA) reduced polyuria in rats with renal ischemia-reperfusion (I/R) injury. LCA increased abundance of aquaporin-2 (AQP2) protein and upregulated hypoxia-inducible factor (HIF)-1α protein expression in association with decreased NF-κB p65 and IL-1ß. After I/R, mice with tgr5 gene deficiency exhibited more severe decreases in AQP2 and HIF-1α protein abundance and inflammatory responses. TGR5 activation exhibits a protective role in acute renal injury induced by I/R.