Highly Light-Harvesting MOF-on-MOF Heterostructure: Cascading Functionality to Flexible Photogating of Organic Photoelectrochemical Transistor and Bienzyme Cascade Detection.

Recently, organic photoelectrochemical transistor (OPECT) bioanalysis has become a prominent technique for the high-performance detection of biomolecules. However, as a sensitive index of the OPECT, the dynamic regulation transconductance (gm) is still severely deficient. Herein, this work reports a new photosensitive metal-organic framework (MOF-on-MOF) heterostructure for the effective modulation of maximum gm and natural bienzyme interfacing toward choline detection. Specifically, the bidentate ligand MOF (b-MOF) was assembled onto the UiO-66 MOF (u-MOF) by a modular assembly method, which could facilitate the charge separation and generate enhanced photocurrents and offer a biophilic environment for the immobilization of choline oxidase (ChOx) and horseradish peroxidase (HRP) through hydrogen-bonded bridges. The transconductance of the OPECT could be flexibly altered by increased light intensity to maximal value at zero gate bias, and sensitive choline detection was achieved with a detection limit of 0.2 µM. This work reveals the potential of MOF-on-MOF heterostructures for futuristic optobioelectronics.

Sirtuin 6 protects against podocyte injury by blocking the renin-angiotensin system by inhibiting the Wnt1/ß-catenin pathway.

Sirtuins (Sirts) are a family of nicotinamide adenine dinucleotide-dependent protein deacetylases that share diverse cellular functions. Increasing evidence shows that Sirts play a critical role in podocyte injury, which is a major determinant of proteinuria-associated renal disease. Membranous nephropathy (MN) is a typical glomerular disease in which podocyte damage mediates proteinuria development. In this study we investigated the molecular mechanisms underlying the regulatory roles of Sirt in podocyte injury in MN patients, rats with cationic bovine serum albumin (CBSA)-induced MN and zymosan activation serum (ZAS)-stimulated podocytes. Compared with healthy controls, MN patients showed significant reduction in intrarenal Sirt1 and Sirt6 protein expression. In CBSA-induced MN rats, significant reduction in intrarenal Sirt1, Sirt3 and Sirt6 protein expression was observed. However, only significant decrease in Sirt6 protein expression was found in ZAS-stimulated podocytes. MN patients showed significantly upregulated protein expression of Wnt1 and ß-catenin and renin-angiotensin system (RAS) components in glomeruli. CBSA-induced MN rats exhibited significantly upregulated protein expression of intrarenal Wnt1 and ß-catenin and their downstream gene products as well as RAS components. Similar results were observed in ZAS-stimulated podocytes. In ZAS-stimulated podocytes, treatment with a specific Sirt6 activator UBCS039 preserved the protein expression of podocin, nephrin and podocalyxin, accompanied by significant inhibition of the protein expression of ß-catenin and its downstream gene products, including Snail1 and Twist; treatment with a ß-catenin inhibitor ICG-001 significantly preserved the expression of podocyte-specific proteins and inhibited the upregulation of downstream ß-catenin gene products accompanied by significant suppression of the protein expression of RAS components. Thus, we demonstrate that Sirt6 ameliorates podocyte injury by blocking RAS signalling via the Wnt1/ß-catenin pathway. Sirt6 is a specific therapeutic target for the treatment of podocyte damage-associated renal disease.

Expression changes of c-Fos and D1R/p-ERK1/2 signal pathways in nucleus accumbens of rats after ketamine abuse.

Ketamine is a commonly used dissociative anesthetic in clinical applications. However, the abuse potential has posted limits to its use and the mechanism remains to be studied. We aimed to investigate the changes of dopamine D1 receptors (D1R), phosphorylation of extracellular-regulated protein kinase 1/2 (p-ERK1/2), and c-Fos expression in the nucleus accumbens (NAc) of ketamine abuse rats. Ketamine induced severe anxiety in rats, as shown by an open field test. Nissl staining demonstrated clearly different morphologies between neurons of ketamine abuse rats and normal rats. The molecular expression changes were examined using immunohistochemistry assay and western blotting. D1R, p-ERK1/2, and c-Fos were significantly highly-expressed in NAc during ketamine exposure and were decreased by D1R antagonist SCH23390 and MAPK kinases inhibitor U0126. Taken together, the results suggest that ketamine abuse may induce the overexpression of c-Fos in NAc by up-regulating the expression of D1R and p-ERK1/2.

Intrarenal 1-methoxypyrene, an aryl hydrocarbon receptor agonist, mediates progressive tubulointerstitial fibrosis in mice.

Recent studies have shown that endogenous metabolites act via aryl hydrocarbon receptor (AhR) signalling pathway in tubulointerstitial fibrosis (TIF) pathogenesis. However, the mechanisms underlying endogenous metabolite-mediated AhR activation are poorly characterised. In this study, we conducted untargeted metabolomics analysis to identify the significantly altered intrarenal metabolites in a mouse model of unilateral ureteral obstruction (UUO). We found that the levels of the metabolite 1-methoxypyrene (MP) and the mRNA expression of AhR and its target genes CYP1A1, CYP1A2, CYP1B1 and COX-2 were progressively increased in the obstructed kidney at Weeks 1, 2 and 3. Furthermore, these changes were positively correlated with progressive TIF in UUO mice. In NRK-52E, RAW 264.7 and NRK-49F cells, MP dose-dependently upregulated the mRNA expression of AhR and its four target genes and the protein expression of nuclear AhR, accompanied by the upregulated protein expression of collagen I, α-SMA and fibronectin, as well as downregulated E-cadherin expression. Consistently, oral administration of MP in mice progressively enhanced AhR activity and upregulated profibrotic protein expression in the kidneys; these effects were partially inhibited by AhR knockdown in MP-treated mice and cell lines. In addition, we screened and identified erythro-guaiacylglycerol-ß-ferulic acid ether (GFA), which was isolated from Semen plantaginis, as a new AhR antagonist. GFA significantly attenuated TIF in MP-treated NRK-52E cells and mice by partially antagonising AhR activity. Our results suggest that MP activates AhR signalling, thus mediating TIF through epithelial-mesenchymal transition and macrophage-myofibroblast transition. MP is a crucial metabolite that contributes to TIF via AhR signalling pathway.

Gut microbiota-derived tryptophan metabolism mediates renal fibrosis by aryl hydrocarbon receptor signaling activation.

The gut microbiota has a crucial effect on regulating the intestinal mucosal immunity and maintaining intestinal homeostasis both in health and in disease state. Many effects are mediated by gut microbiota-derived metabolites and tryptophan, an essential aromatic amino acid, is considered important among many metabolites in the crosstalk between gut microbiota and the host. Kynurenine, serotonin, and indole derivatives are derived from the three major tryptophan metabolism pathways modulated by gut microbiota directly or indirectly. Aryl hydrocarbon receptor (AHR) is a cytoplasmic ligand-activated transcription factor involved in multiple cellular processes. Tryptophan metabolites as ligands can activate AHR signaling in various diseases such as inflammation, oxidative stress injury, cancer, aging-related diseases, cardiovascular diseases (CVD), and chronic kidney diseases (CKD). Accumulated uremic toxins in the body fluids of CKD patients activate AHR and affect disease progression. In this review, we will elucidate the relationship between gut microbiota-derived uremic toxins by tryptophan metabolism and AHR activation in CKD and its complications. This review will provide therapeutic avenues for targeting CKD and concurrently present challenges and opportunities for designing new therapeutic strategies against renal fibrosis.

The value of nurse-led anthropometric and oropharyngeal measurements combined with STOP-Bang questionnaire in screening for obstructive sleep apnea in patients with acute coronary syndrome: a prospective cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) is a modifiable risk factor for acute coronary syndrome (ACS), with high prevalence but low diagnostic rates. Therefore, it is particularly important to develop strategies for better screening for OSA in newly admitted ACS patients. METHODS: From March 2017 to October 2019, consecutive eligible patients with ACS underwent cardiorespiratory polygraphy during hospitalization. OSA was defined as an apnea-hypopnea index (AHI) ≥ 15 events/h. All anthropometric and oropharyngeal parameters are measured by specialist nurses. RESULTS: Finally, 761 ACS patients were recruited in the present study. Prevalence of moderate/severe OSA was 53.2% based on diagnostic criteria of AHI ≥ 15. Correlation analysis illustrated that AHI was positively correlated with anthropometric characteristics. In the multivariate model, only micrognathia (OR 2.02, 95% CI 1.02-4.00, P = 0.044), waist circumference (OR 1.08, 95% CI 1.04-1.11, P < 0.001), and STOP-BANG Questionnaire (SBQ) score (OR 1.45, 95% CI 1.27-1.66, P < 0.001) were independently associated with the prevalence of OSA. Receiver operating characteristic curve (ROC) analysis showed that the area under curve (AUC) of multivariable joint diagnosis (waist circumference, micrognathia combined with SBQ) was significantly better than the AUC of Epworth Sleepiness Scale (ESS) and SBQ (p < 0.0001 and p = 0.0002, respectively), and the results showed that AUC was 0.728. Under the optimal truncation value, the sensitivity was 73%, and the specificity was 61%, which was higher than the single index. Finally, we also constructed a nomogram model based on multiple logistic regression, to easily determine the probability of OSA in ACS patients. CONCLUSIONS: The new screening tool has greater power than single questionnaire or measurements in screening of OSA among ACS patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03362385, registered December 5, 2017.

Occurrence of Leaf Spot Caused by Diaporthe phaseolorum on Bletilla striata in China.

Bletilla striata (Thunb.) Rchb. f. (Orchidaceae) is a traditional Chinese medicinal plant widely distributed in eastern and southern Asia. In April of 2020, a leaf spot disease on B. striata was observed in plant nurseries in Guilin, Guangxi Province, China. Disease incidence was estimated at approximately 20% (n = 150 plants) across the survey area (~ 0.3 ha). The initial symptoms were small, reddish to brown spots, circular or irregular in shape. Subsequently, they developed into large dark brown, irregular lesions. As the lesions coalesced, leaves withered and defoliated. To isolate the causal agent, eighteen small pieces (~ 5 mm2) were collected from the margin of the necrotic lesions on Chinese ground orchid, surface disinfected (2 min in 1% NaOCl, and rinsed three times in sterile water), and placed on potato dextrose agar (PDA) at 26°C for 3 days. Hyphal tips were transferred to PDA to obtain pure cultures. Twelve isolates were obtained, of which eight isolates had similar morphological characteristics. After 7 days growth on PDA, colonies were grayish-white, fluffy, with white aerial mycelium. After 3 weeks, colonies formed white aerial mycelial mats, and pycnidia developed. The α-conidia were abundant, hyaline, aseptate, ellipsoidal to fusiform, measuring 4.6 to 6.7 µm × 2.1 to 3.0 µm (n = 55), whereas the ß-conidia were hyaline, long, slender, straight or curved, measuring 10.3 to 17.2 µm × 0.9 to 1.8 µm (n = 59). Morphological features were similar to Diaporthe sp. (Santos et al. 2011, Udayanga et al. 2015). For further molecular identification, DNA was extracted from the mycelia of the representative isolate BJ26.3 following the CTAB (cetyltrimethylammonium bromide) method (Guo et al. 2000). The internal transcribed spacer (ITS) region, partial translational elongation factor subunit 1-α (EF-1α), calmodulin (CAL) , histone H3 (HIS3), ß-tubulin (TUB) genes were amplified and sequenced using the primer pairs ITS1/ITS4, EF1-728F/EF1-986R, CAL-228F/CAL-737R, CYLH3F/H3-1b, and Bt2a/Bt2b, respectively (White et al. 1990, Guarnaccia et al. 2018). The obtained sequences were deposited in NCBI GenBank under the following accession numbers: OK560457, OK539595, OK539592, OK506726, OK539598. BLAST analysis of the deposited sequences showed 99 to 100% identity with accession numbers KC343177 (563/566 bp), KC343903 (521/523 bp), KC343419 (423/427 bp), KC343661 (340/340 bp), KC344145 (658/662 bp) of D. phaseolorum CBS 127465 (Guarnaccia et al. 2018). In addition, a phylogenetic analysis using concatenated sequences confirmed BJ26.3 as D. phaseolorum. Furthermore, pathogenicity tests were carried out on 1.5-year-old B. striata plants. Healthy leaves on three plants (1 leaf per plant) were inoculated with 5 × 5 mm mycelial discs of strain BJ-26.3 from 3-day-old PDA cultures. Another three plants treated with sterile water served as the control. All plants were covered with transparent plastic bags and maintained in a greenhouse at 26°C with a 12 h photoperiod. Nine days post-inoculation, the inoculated leaves showed leaf spot symptoms, while the control plants remained healthy. The experiments repeated three times showed similar results. Finally, D. phaseolorum was consistently re-isolated from the infected leaves and confirmed by morphology and sequencing, fulfilling Koch's postulates. To our knowledge, this is the first report of D. phaseolorum causing leaf spot of B. striata worldwide. This study might provide important information for growers to manage this disease.

Identification of Neofusicoccum parvum as the causative agent of leaf spot disease on Bletilla striata in China.

Bletilla striata (Thunb.) Rchb. f. (Orchidaceae) is an essential traditional Chinese medicinal plant used to treat hemorrhage, swelling, inflammation, ulcers, and pulmonary diseases (Xu et al. 2019). In April of 2020, an unknown leaf spot disease was observed on B. striata in a plantation (~ 0.2 ha) in Nanning, Guangxi province, China. Disease incidence was estimated at approximately 25% (n = 150 plants). The initial symptoms were small brown circular spots, which then expanded into reddish to brown, circular to irregular lesions 5-10 mm in diameter. As the disease developed, the whole leaf became densely covered with lesions. Finally, the lesions coalesced, killing the leaf and resulting in defoliation. To isolate the causal agent, six symptomatic leaves were collected from individual plants. Small pieces (~ 5 mm2) were cut from the margin of the necrotic lesions (n = 18), disinfected in 1% NaOCl for 2 min before rinsing three times in sterile water, and placed on potato dextrose agar (PDA) at 26°C for 3 days. Hyphal tips from the resulting cultures were transferred to PDA to obtain pure cultures. Fifteen isolates were obtained, of which twelve isolates exhibited similar morphology. Colonies on PDA were initially white, then turned dark gray after 7 days. Pycnidia were produced on the surface of PDA after 50 days. Conidia were hyaline, aseptate, ellipsoidal to fusiform, externally smooth, thin-walled, and measuring 11.5 to 15.2 × 4.9 to 6.1 µm (mean ± SD: 13.4 ± 1.0 × 5.4 ± 0.3 µm, n = 60). Morphological features were similar to N. parvum (Phillips et al. 2013). For further molecular identification, the internal transcribed spacer (ITS) region, partial translational elongation factor subunit 1-α (EF-1α), ß-tubulin (TUB2) genes were amplified and sequenced using the primer pairs ITS1/ITS4 (White et al. 1990), EF1-728F (Carbone and Kohn 1999)/EF-2 (O'Donnell et al. 1998), and Bt2a/Bt2b (Glass and Donaldson 1995), respectively. Sequences of the two isolates BJ-111.1 and BJ-111.4 were deposited in NCBI GenBank under the following accession numbers: OM348509-10, OM397537-40. The obtained ITS, EF1-α, and TUB2 sequences showed 99% (514/516, and 513/516 bp), 99% (275/276, and 274/275 bp), and 99% (429/431, and 429/430 bp) homology with several GenBank sequences of the ex-type strain N. parvum CMW 9081 (AY236943, AY236888, and AY236917, respectively) (Zhang et al. 2017). In addition, a phylogenetic analysis confirmed the isolates as N. parvum. Therefore, the isolates were identified as N. parvum based on morphological and molecular evidence. Furthermore, pathogenicity tests were carried out on 1.5-year-old B. striata plants. Healthy leaves on six plants (1 leaf per plant) were inoculated with a 10-µl droplet of conidial suspensions (106 conidia/mL). Three plants treated with sterile water served as the control. All plants were covered with transparent plastic bags and incubated in a greenhouse at 26°C with a 12 h photoperiod. Six days post-inoculation, the inoculated leaves showed leaf spot symptoms, while the control plants remained healthy. The experiments repeated three times showed similar results. Finally, N. parvum was consistently re-isolated from the infected leaves and confirmed by morphology and sequencing, fulfilling Koch's postulates. No fungus was isolated from the controls. To our knowledge, this is the first report of N. parvum causing leaf spot of B. striata worldwide. This result will help develop disease management strategies against this pathogen.

Exogenous Melatonin Enhances Photosynthetic Capacity and Related Gene Expression in A Dose-Dependent Manner in the Tea Plant (Camellia sinensis (L.) Kuntze).

The enhancement of photosynthesis of tea leaves can increase tea yield. In order to explore the regulation mechanism of exogenous melatonin (MT) on the photosynthetic characteristics of tea plants, tea variety 'Zhongcha 108' was used as the experimental material in this study. The effects of different concentrations (0, 0.2, 0.3, 0.4 mM) of melatonin on the chlorophyll (Chl) content, stomatal opening, photosynthetic and fluorescence parameters, antioxidant enzyme activity, and related gene expression of tea plants were detected and analyzed. The results showed that under 0.2-mM MT treatment, chlorophyll (Chl) content, photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) improved, accompanied by a decrease in stomata density and increase in stomata area. Zero point two millimolar MT increased Chl fluorescence level and superoxide dismutase (SOD) activity, and reduced hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents, indicating that MT alleviated PSII inhibition and improved photochemical efficiency. At the same time, 0.2 mM MT induced the expression of genes involved in photosynthesis and chlorophyll metabolism to varying degrees. The study demonstrated that MT can effectively enhance the photosynthetic capacity of tea plants in a dose-dependent manner. These results may promote a comprehensive understanding of the potential regulatory mechanism of exogenous MT on photosynthesis in tea plants.

Deciphering the cellular mechanisms underlying fibrosis-associated diseases and therapeutic avenues.

Fibrosis is the excessive deposition of extracellular matrix components, which results in disruption of tissue architecture and loss of organ function. Fibrosis leads to high morbidity and mortality worldwide, mainly due to the lack of effective therapeutic strategies against fibrosis. It is generally accepted that fibrosis occurs during an aberrant wound healing process and shares a common pathogenesis across different organs such as the heart, liver, kidney, and lung. A better understanding of the fibrosis-related cellular and molecular mechanisms will be helpful for development of targeted drug therapies. Extensive studies revealed that numerous mediators contributed to fibrogenesis, suggesting that targeting these mediators may be an effective therapeutic strategy for antifibrosis. In this review, we describe a number of mediators involved in tissue fibrosis, including aryl hydrocarbon receptor, Yes-associated protein, cannabinoid receptors, angiopoietin-like protein 2, high mobility group box 1, angiotensin-converting enzyme 2, sphingosine 1-phosphate receptor-1, SH2 domain-containing phosphatase-2, and long non-coding RNAs, with the goal that drugs targeting these important mediators might exhibit a beneficial effect on antifibrosis. In addition, these mediators show profibrotic effects on multiple tissues, suggesting that targeting these mediators will exert antifibrotic effects on different organs. Furthermore, we present a variety of compounds that exhibit therapeutic effects against fibrosis. This review suggests therapeutic avenues for targeting organ fibrosis and concurrently identifies challenges and opportunities for designing new therapeutic strategies against fibrosis.

First Report of Anthracnose on Bletilla striata Caused by Colletotrichum fructicola in China.

Bletilla striata (Thunb.) Rchb. f. (Orchidaceae) is a traditional Chinese medicinal plant. In April 2018 and 2019, a leaf spot disease was observed on ∼20% of B. striata plants in two fields (∼1.4 h) in Guilin, Guangxi Province, China (Fig.1 A). Small, circular, brown spots were initially observed on the leaf surfaces, which progressively expanded into large, sunken, dark brown, necrotic areas. As the disease progressed, lesions merged into large, irregular spots, ultimately resulting in abscission. To determine the causal agent, small pieces (5 mm x 5 mm) were collected from the infected leaf tissues (n = 18), surface sterilized in 1% NaOCl for 2 min, and rinsed three times with sterile water. Then, the tissues were placed on potato dextrose agar (PDA) with chloramphenicol (0.1 g/L) and incubated under 12 h photoperiod at 26°C for 3 days. Seventeen isolates were obtained, of which twelve isolates with similar morphological characteristics were obtained from the germinated spores on PDA. Seven-day-old colonies on PDA appeared cottony, pale white to pale gray from above, and grayish-green from below. Conidia of strain BJ-101.3 were hyaline, aseptate, straight, and cylindrical, with rounded ends (Fig.1 E-G), measuring 11.3 to 15.9 µm × 4.0 to 6.4 µm (n = 50). Appressoria were brown to dark brown, with different shapes and a smooth edge (Fig.1 H-I), measuring 6.3 to 10.0 µm × 4.1 to 8.0 µm (n = 50). Morphological features were similar to C. gloeosporioides species complex (Weir et al. 2012, Fuentes-Aragón et al. 2018). For molecular identification, DNA was extracted from two isolates BJ-101.3 and BJ-101.13, following the CTAB method (Guo et al. 2000). The internal transcribed spacer (ITS) region, partial actin (ACT), calmodulin (CAL), chitin synthase (CHS-1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), manganese superoxide dismutase (SOD2), beta-tubulin (TUB2), glutamine synthetase (GS), and Apn2-Mat1-2 intergenic spacer and partial mating-type (ApMat) genes were amplified by PCR and sequenced (Weir et al. 2012, Silva et al. 2012, Vieira et al. 2017). The obtained sequences were deposited in GenBank (MW386818, MW386819, MW403508 to MW403519, and MW888410 to MW888413). BLASTN analysis of the obtained sequences showed 99% identity with those of C. fructicola (JX010165，JX010033, FJ917508, FJ907426, JX009866, JX010095, JX010327, JX010405, JQ807838) (Weir et al. 2012, Liu et al. 2015). A phylogenetic tree based on the concatenated sequences confirmed the isolates as C. fructicola (Fig.2). Furthermore, pathogenicity tests were conducted on six 1.5-year-old B. striata plants. Healthy leaves on the plants were inoculated with the conidial suspensions (106 conidia/mL; 10 µL) of the strains BJ-101.3 and BJ101.13. The conidial suspension of each isolate was inoculated onto at least three leaves. Another three plants inoculated with sterile water served as the control. All plants were covered with transparent plastic bags and incubated in a greenhouse at 26°C for 14 days with a 12 h photoperiod. Nine days post-inoculation, the inoculated leaves showed leaf spot symptoms, while the control plants remained symptomless (Fig.1 B-C). The experiments repeated three times showed similar results. Finally, C. fructicola was consistently reisolated from the infected leaves and confirmed by morphology and sequencing, fulfilling Koch's postulates. The outcome of this study will help in developing effective management measures against anthracnose of B. striata.

Hybrid nano-textured nanogenerator and self-powered sensor for on-skin triggered biomechanical motions.

Researchers have made a lot of effort for the lightweight and high flexibility of wearable electronic devices, which also requires the associated energy harvesting equipment to have ultra-thin thickness and high stretchability. Therefore, a piezoelectric-triboelectric hybrid self-powered sensor (PTHS) has been proposed which can be used as the second layer of the human body. This elastic PTHS can even work on a person's fingers without disturbing the body's movements. The open circuit voltage and short circuit current of devices with a projected area of 30 mm × 25 mm can reach 1.2 V and 30 nA, respectively. Two piezoelectrically-triboelectrically sensors with machine learning optimized identification strategies were experimentally proven as the potential applications of the PTHS. The PTHS's ultra-thin thickness, high stretchability and superior geometry control features are promising in electronic skin, artificial muscle and soft robotics. The novelty of this work is that a smart mask integrated with PTHS can generate a signal of the hybrid sensor for the biomechanical motion classifier. After suitable training, an overall accuracy of 87.9% using long short-term memory can be achieved.

Safety and satisfaction of myopic small-incision lenticule extraction combined with monovision.

BACKGROUND: To investigate the safety and optical quality of small-incision lenticule extraction (SMILE) combined with monovision, and patient satisfaction with the procedure. METHODS: The present study assessed a non-random case series involving 60 eyes of 30 patients (mean age 45.53 ± 3.20 years [range 41 to 52 years]) treated bilaterally using the VisuMax 500 system (Carl Zeiss Meditec, Jena, Germany) between January and July 2016. The target refraction was plano for the distance eye, and between - 0.5 and - 1.75 diopters (D) for the near eye. Visual acuity, refraction errors, ocular aberrations, and satisfaction questionnaire scores were calculated 1 year after surgery. RESULTS: All surgeries were uneventful, with a mean safety index of 1.03 and 1.04 in dominant and nondominant eyes, respectively. Binocular uncorrected distance visual acuity of all patients was ≥20/32, while binocular uncorrected near visual acuity was ≥20/40 1 year postoperatively. Higher-order aberration (0.45 ± 0.14, 0.51 ± 0.15 µm), spherical (0.18 ± 0.15, 0.21 ± 0.14 µm) and coma aberration (0.31 ± 0.16, 0.27 ± 0.17 µm) were identical between dominant and nondominant eyes after surgery. The overall satisfaction rate was 86.7% (26/30), with large contributions from age (OR = 1.76 95% CI: 1.03-2.53; P = 0.036). Binocular uncorrected distance visual acuity was related to preoperative spherical diopter (r = - 0.500; P = 0.005). CONCLUSIONS: Monovision appears to be a safe and effective option for myopia patients with presbyopia who are considering the SMILE procedure. Patients with younger age were more satisfied with the procedure.

Urinary biomarker and treatment mechanism of Rhizoma Alismatis on hyperlipidemia.

Rhizoma Alismatis (RA), a diuretic in Asia and Europe, was found to possess anti-hyperlipidemic activity. Since the biomarkers and mechanisms of RA in the treatment of hyperlipidemia are inadequate, ultra-performance liquid chromatography coupled with quadrupole time-of-flight synapt high-definition mass spectrometry and multivariate data analysis were employed to investigate the urinary metabolomics of RA on hyperlipidemic rats induced by high-fat diet. The metabolic profile of RA-treated hyperlipidemic group located between control and diet-induced hyperlipidemic groups. Nineteen metabolites with significant fluctuations were identified as potential biomarkers related to the hyperlipidemia and anti-hyperlipidemia of RA using partial least-squares-discriminate analysis, heatmap analysis and correlation coefficient analysis. The fluctuations of these biomarkers represented disturbances in amino acid metabolism, purine metabolism, pyrimidine metabolism and energy metabolism. After RA treatment, these perturbed metabolites were restored to normal or nearly normal levels. RA can alleviate high-fat diet-induced dysfunctions in these metabolic pathways.

miR-320b suppresses cell proliferation by targeting c-Myc in human colorectal cancer cells.

BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs that potentially play a critical role in tumorigenesis. Mounting evidence indicates that one specific miRNA: miR-320b is down regulated in numerous human cancers, including colorectal cancer (CRC); making the hypothesis that miR-320b may play a key role in tumorigenesis plausible. However, its role in carcinogenesis remains poorly defined. The goal of this study is to better clarify the role of miR-320b in tumor growth of CRC. METHODS: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was conducted to detect the expression of miR-320b in CRC tissues and 5 CRC cell lines. The effect of miR-320b on cell proliferation was analyzed in vitro and in vivo. Furthermore, a luciferase reporter assay was performed to measure the target effects of miR-320b. Lastly, the messenger RNA (mRNA) and protein levels of the gene c-MYC were measured in CRC cell lines and tissues by qRT-PCR, and confirmed via Western blot and Immunohistochemical (IHC) staining. RESULTS: The results presented here showed that miR-320b expression was down regulated in both CRC tissues and cells. Overexpression of miR-320b in CRC cells was statistically correlated with a decrease of cell growth in vitro and in vivo, while c-MYC was identified as a target gene of miR-320b in CRC. Furthermore, it was found that up-regulation of c-Myc can attenuate the effects induced by miR-320b. CONCLUSIONS: Our identification of c-MYC as a target gene of miR-320b provides new insights into the pathophysiology of CRC proliferation, and identifies miR-320b as a novel therapeutic target for the treatment of CRC.

[Molecular classification of colorectal carcinoma based on integration of gene expression profile and copy number variation].

OBJECTIVE: To classify colorectal carcinoma (CRC) by TNM staging integrated with the gene expression profile and copy number variation (CNV). METHODS: Profile data of gene expression and CNV of CRC were downloaded from public database and processed with batch bias adjustment, quartile normalization, missing value estimation and feature filtration. The processed profiles of mRNA and CNV were introduced into the codes of Bayesian consensus clustering (BCC) method and were used to calculate the subclasses of CRC. With the follow-up information of disease free survival of CRC patients, the prognostic values of the subclasses was investigated and the software of function enrichment analysis was employed to discover the major pathway signaling to each interesting subclass. All statistic analyses were performed under R-3.0.1 environment or by using SPSS 16.0 software. RESULTS: Profile data of gene expression and corresponding CNV from 335 CRC patients with TNM stage Ⅱ-Ⅲ and followed-up information were obtained. After feature filtering, the profiles contained 1578 probes of mRNA and 345 location of CNV. Four CRC subclasses were identified by the integrative analysis with BCC, and the concordances of BCC subclasses and each of gene-based subclasses (Cramer's V=0.49), CNV-based subclasses (Cramer's V=0.51) and Marisa's subclasses (Cramer's V=0.32) were statistically significant (Ps<0.001). Among BCC subclasses, BCC-I had a favorable prognosis, while BCC-Ⅳ had more unfavorable prognosis. The differences of prognosis were significant among BCC-I, BCC-(Ⅱ+Ⅲ) and BCC-Ⅳ with an overall log-rank P<0.001. The top enriched function was DNA damage and repair signaling when BCC-I compared to BCC-Ⅳ, and the new subgroups classified by the genes associated with enriched signaling had the better prognostic value than BCC subclasses but both of them were significantly correlated (Cramer's V=0.39, P<0.001). CONCLUSION: BCC method is effective to integrate multi-type genomic data for molecular classification of colorectal carcinoma, and the BCC-Ⅳ subclass has poor prognosis, which may be associated with the decreased repairing function of DNA damage.

Bile acid metabolism in health and ageing-related diseases.

Bile acids (BAs) have surpassed their traditional roles as lipid solubilizers and regulators of BA homeostasis to emerge as important signalling molecules. Recent research has revealed a connection between microbial dysbiosis and metabolism disruption of BAs, which in turn impacts ageing-related diseases. The human BAs pool is primarily composed of primary BAs and their conjugates, with a smaller proportion consisting of secondary BAs. These different BAs exert complex effects on health and ageing-related diseases through several key nuclear receptors, such as farnesoid X receptor and Takeda G protein-coupled receptor 5. However, the underlying molecular mechanisms of these effects are still debated. Therefore, the modulation of signalling pathways by regulating synthesis and composition of BAs represents an interesting and novel direction for potential therapies of ageing-related diseases. This review provides an overview of synthesis and transportion of BAs in the healthy body, emphasizing its dependence on microbial community metabolic capacity. Additionally, the review also explores how ageing and ageing-related diseases affect metabolism and composition of BAs. Understanding BA metabolism network and the impact of their nuclear receptors, such as farnesoid X receptor and G protein-coupled receptor 5 agonists, paves the way for developing therapeutic agents for targeting BA metabolism in various ageing-related diseases, such as metabolic disorder, hepatic injury, cardiovascular disease, renal damage and neurodegenerative disease.

Lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells is inhibited by microRNA-494-3p via targeting lipoprotein-associated phospholipase A2.

BACKGROUND: Gram-negative bacterial lipopolysaccharide (LPS) is a major component of inflammation and plays a key role in the pathogenesis of sepsis. According to our previous study, the expression of lipoprotein-associated phospholipase A2 (Lp-PLA2) is significantly upregulated in septic patients and is positively correlated with the severity of this disease. Herein, we investigated the potential roles of Lp-PLA2-targeting microRNAs (miRNAs) in LPS-induced inflammation in murine mononuclear macrophages (RAW264.7 cells). METHODS: In LPS-stimulated RAW264.7 cells, Lp-PLA2 was confirmed to be expressed during the inflammatory response. The function of microRNA-494-3p (miR-494-3p) in the LPS-induced inflammatory response of RAW264.7 cells was determined by the transfection of a miR-494-3p mimic or inhibitor in vitro. RESULTS: Compared to the control, LPS induced a significant increase in the Lp-PLA2 level, which was accompanied by the release of inflammatory mediators. The bioinformatics and qRT‒PCR results indicated that the miR-494-3p level was associated with Lp-PLA2 expression in the LPS-induced inflammatory response of RAW264.7 cells. Dual-luciferase reporter assay results confirmed that the 3'-UTR of Lp-PLA2 was a functional target of microRNA-494-3p. During the LPS-induced inflammatory response of RAW264.7 cells, targeting Lp-PLA2 and transfecting miR-494-3p mimics significantly upregulated the expression of miR-494-3p, leading to a reduction in the release of inflammatory factors and conferring a protective effect on LPS-stimulated RAW264.7 cells. CONCLUSION: By targeting Lp-PLA2, miR-494-3p suppresses Lp-PLA2 secretion, thereby alleviating LPS-induced inflammation, which indicates that miR-494-3p may be a potential target for sepsis treatment.

Lactobacillus species ameliorate membranous nephropathy through inhibiting the aryl hydrocarbon receptor pathway via tryptophan-produced indole metabolites.

BACKGROUND AND PURPOSE: Membranous nephropathy (MN) is an immune-mediated glomerular disease in adults. Antibody- and antigen-bonding mechanisms have been largely clarified, but the subepithelium immune complex deposition-mediated downstream molecular mechanisms are currently unresolved. Increasing evidence has suggested that gut microbiota contribute to MN pathogenesis. EXPERIMENTAL APPROACH: In this study, we identified alterations in faecal gut microbiota and serum metabolites that mediate an aryl hydrocarbon receptor (AhR) mechanism in cationic bovine serum albumin (CBSA)-induced MN rats and in patients with idiopathic MN (IMN). KEY RESULTS: Impaired renal function correlated with the relative abundance of reduced faecal probiotics, Lactobacillus and Bifidobacterium, and altered serum levels of tryptophan-produced indole derivatives (TPIDs) in MN rats. Further results showed that reduced relative abundance of five probiotics, namely Lactobacillus johnsonii, Lactobacillus murinus, Lactobacillus vaginalis, Lactobacillus reuteri and Bifidobacterium animalis, positively correlated with decreased levels of indole-3-pyruvic acid, indole-3-aldehyde and tryptamine and negatively correlated with increased levels of indole-3-lactic acid and indole-3-acetic acid in serum of MN rats. Altered five probiotics and five TPIDs also were observed in patients with IMN. Further studies showed that MN rats exhibited a significant increase in intrarenal mRNA expression of AhR and its target genes CYP1A1, CYP1A2 and CYP1B1, which were accompanied by protein expression of down-regulated cytoplasmic AhR, but up-regulated nuclear AhR, in MN rats and IMN patients. CONCLUSION AND IMPLICATIONS: Activation of the intrarenal AhR signalling pathway may involve five TPIDs. These data suggest that gut microbiota could influence MN through TPIDs that engage host receptors.