Sexually concordant selection on floral traits despite greater opportunity for selection through male fitness.

Pollinators are important drivers of floral trait evolution, yet plant populations are not always perfectly adapted to their pollinators. Such apparent maladaptation may result from conflicting selection through male and female sexual functions in hermaphrodites. We studied sex-specific mating patterns and phenotypic selection on floral traits in Aconitum gymnandrum. After genotyping 1786 offspring, we partitioned individual fitness into sex-specific selfed and outcrossed components and estimated phenotypic selection acting through each. Relative fitness increased with increasing mate number, and more so for male function. This led to greater opportunity for selection through outcrossed male fitness, though patterns of phenotypic selection on floral traits tended to be similar, and with better support for selection through female rather than male fitness components. We detected directional selection through one or more fitness component for larger flower number, larger flowers, and more negative nectar gradients within inflorescences. Our results are consistent with Bateman's principles for sex-specific mating patterns and illustrate that, despite the expected difference in opportunity for selection, patterns of variation in selection across traits can be rather similar for the male and female sexual functions. These results shed new light on the effect of sexual selection on the evolution of floral traits.

Deep learning enables the discovery of a novel cuproptosis-inducing molecule for the inhibition of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers in the world. The therapeutic outlook for HCC patients has significantly improved with the advent and development of systematic and targeted therapies such as sorafenib and lenvatinib; however, the rise of drug resistance and the high mortality rate necessitate the continuous discovery of effective targeting agents. To discover novel anti-HCC compounds, we first constructed a deep learning-based chemical representation model to screen more than 6 million compounds in the ZINC15 drug-like library. We successfully identified LGOd1 as a novel anticancer agent with a characteristic levoglucosenone (LGO) scaffold. The mechanistic studies revealed that LGOd1 treatment leads to HCC cell death by interfering with cellular copper homeostasis, which is similar to a recently reported copper-dependent cell death named cuproptosis. While the prototypical cuproptosis is brought on by copper ionophore-induced copper overload, mechanistic studies indicated that LGOd1 does not act as a copper ionophore, but most likely by interacting with the copper chaperone protein CCS, thus LGOd1 represents a potentially new class of compounds with unique cuproptosis-inducing property. In summary, our findings highlight the critical role of bioavailable copper in the regulation of cell death and represent a novel route of cuproptosis induction.

Effect of lung metastasis on the treatment and prognosis of patients with gestational trophoblastic neoplasia: A systematic review and meta-analysis.

INTRODUCTION: Gestational trophoblastic neoplasia (GTN) is a highly invasive tumor, mainly spreading to the lungs. However, lung metastasis in GTN is usually not considered as an adverse prognostic factor. Therefore, the aim of this study was to summarize the results of previous studies and evaluate the effects of lung metastasis on the treatment and prognosis of GTN. MATERIAL AND METHODS: The study was prospectively registered in PROSPERO (CRD42023372371). Electronic databases including PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and China Biomedical Literature Database were used for a systematical search of relevant studies published up to November 21, 2022. The observational studies reporting the clinical outcomes of GTN patients with and without lung metastasis were selected. The incidences of resistance, relapse, and mortality of GTN patients were extracted and successively grouped based on the presence of lung metastasis. The pooled relative risks (RRs) and 95% confidence interval (95% CI) of the eligible studies were calculated. The qualities of included studies were assessed with the Newcastle-Ottawa Scale and the certainty of evidence was graded based on the GRADE. The meta-analysis was performed using Stata 12.0 and GradePro software. RESULTS: Five publications with 3629 GTN patients were included. The meta-analysis revealed that the GTN with lung metastasis was strongly correlated with first-line chemoresistance (pooled RR = 1.40, 95% CI: 1.22 to 1.61, p < 0.001), recurrence (pooled RR = 3.03, 95% CI: 1.21 to 7.62, p = 0.018), and disease-specific death (pooled RR = 22.11, 95% CI: 3.37 to 145.08, p = 0.001). Ethnicity was also an important factor and Caucasian GTN patients with lung metastasis showed a higher risk of recurrence as revealed by the subgroup analysis (pooled RR = 5.10, 95% CI: 2.38 to 10.94, p < 0.001). CONCLUSIONS: GTN patients with lung metastasis exhibited a higher risk of chemoresistance, relapse, and disease-specific death. Patients with lung metastasis among the Caucasian population had a higher risk of recurrence than Asian populations. Therefore, the presence of lung metastases might be considered as a high-risk factor for prognosis of GTN and deserves more attention in the choice of first-line chemotherapy regimens and follow-up.

Key enzyme in charge of ketone reabsorption of renal tubular SMCT1 may be a new target in diabetic kidney disease.

OBJECTIVE: A ketogenic diet or mildly increased ketone body levels are beneficial for diabetic kidney disease (DKD) patients. Our previous study has found that sodium-coupled monocarboxylate transporter 1 (SMCT1), a key enzyme in charge of ketone reabsorption, possesses beneficial effects on the function of renal tubular epithelial cells (TECs) in energy crisis. Our present study is to investigate whether SMCT1 is important in maintaining the physiological function of renal tubular and plays a role in DKD. METHODS: We tested the expression of SMCT1 in kidney tissues from DKD patients receiving kidney biopsy as well as diabetes mice. We compared the difference of ß-hydroxybutyrate (ß-HB) levels in serum, urine and kidney tissues between diabetic mice and control. Using recombinant adeno-associated viral vector containing SMCT1 (encoded by Slc5a8 gene), we tested the effect of SMCT1 upregulation on microalbuminuria as well as its effects on mitochondrial energy metabolism in diabetic mice. Then we investigated the role of SMCT1 and its ß-HB reabsorption function in maintaining the physiological function of renal tubular using renal tubule-specific Slc5a8 gene knockout mice. Transcriptomes and proteomics analysis were used to explore the underlying mechanism. RESULTS: SMCT1 downregulation was found in DKD patients as well as in diabetic mice. Moreover, diabetic mice had a decreased renal ß-HB level compared with control, and SMCT1 upregulation could improve microalbuminuria and mitochondrial energy metabolism. In renal tubule-specific Slc5a8 gene knockout mice, microalbuminuria occurred early at 24 weeks of age, accompanied by ATP shortage and metabolic reprogramming in the kidney; however, supplementation with ß-HB precursor substance 1,3-butanediol in food alleviated kidney damage as well as energy metabolic reprogramming. CONCLUSIONS: Decreased SMCT1 expression and its ketone reabsorption function play an important role in the occurrence of DKD. SMCT1 may be a new promising target in treating DKD.

Lean adipose tissue macrophage derived exosome confers immunoregulation to improve wound healing in diabetes.

Chronic non-healing wounds, a prevalent complication of diabetes, are associated with increased mortality in diabetic patients. Excessive accumulation of M1 macrophages in diabetic wounds promotes inflammation and results in dysregulated tissue repair. Adipose tissue macrophages (ATMs) derived from healthy lean donors have the ability to improve glucose tolerance and insulin sensitivity, as well as modulate inflammation. MicroRNAs (miRs), which can be packaged into exosomes (Exos) and secreted from cells, serve as essential regulators of macrophage polarization. Here, we revealed that ATMs isolated from lean mice secrete miRs-containing Exos, which modulate macrophage polarization and promote rapid diabetic wound healing when administered to diabetes-prone db/db mice. The miRs sequence of tissue samples from wounds treated with Exos secreted by lean ATMs (ExosLean) revealed that miR-222-3p was up-regulated. Further analyses showed that inhibiting miR-222-3p using a miR inhibitor impaired the macrophage-reprogramming effect of ExosLean. In the excisional skin wound mouse model, locally inhibiting miR-222-3p disrupted healing dynamics and failed to modulate macrophage polarization. Mechanistic studies revealed a connection between miR-222-3p, Bcl2l11/Bim, an inflammatory response effector, macrophage polarization, and diabetic wound healing. In summary, ExosLean act as positive regulators of macrophage polarization by regulating miR levels in wounds and accelerating wound healing, and thus have important implications for wound management in diabetes.

[Comprehensive evaluation of Pinellia ternata germplasm resources based on phenotypic trait classification].

The evaluation of germplasm resources is the prerequisite for the development, utilization, and conservation of Chinese medicinal resources. The selection of excellent germplasm is the key to the breeding and orderly production of Pinellia ternata. In this study, 21 germplasm materials of P. ternata from major production areas in China were collected and analyzed for population diversity after phenotypic preliminary screening. The results have revealed that the P. ternata population has abundant phenotypic variation, and the phenotypic changes could be divided into five phenotypes in terms of organ trait variation. Further analysis of variation in 20 quantitative traits of the population revealed that the coefficient of variation for adenosine content(339.05%) was the largest, while the coefficient of variation for the underground plant height(16.35%) was the smallest. Correlation analysis showed that there was a strong correlation among various traits, with 52 pairs of traits showing highly significant correlation(P<0.01) and 19 pairs of traits showing a significant correlation(P<0.05). The 21 germplasms in the test could be classified into three major clusters by cluster analysis, with Cluster Ⅱ having the highest number and content of nucleosides, making it suitable for the selection and breeding of P. ternata varieties with high content of nucleosides. The yield in Cluster Ⅲ was higher than that in other groups, making it suitable for the selection and breeding of P. ternata varieties with a high yield. All trait indicators could be simplified into five principal component factors through principal component analysis, and the cumulative contribution rate was up to 86.04%. Further, comprehensive analysis using membership function and stepwise regression analysis identified nine traits, such as plant height, main leaf length, and underground plant height as characteristic indicators for the comprehensive evaluation of germplasm resources of P. ternata. BX007, BX008, and BX005 were identified as germplasms with both high yield and high uridine content, with BX007 having the highest uridine content of 479.51 µg·g~(-1). It belonged to the germplasm of P. ternata with double bulbils and could be cultivated as a potential good variety. Based on the phenotypic classification of P. ternata, systematic resource evaluation was carried out in this study, which could lay a foundation for the excavation of genetic resources and the breeding of new varieties of P. ternata.

Young fibroblast-derived exosomal microRNA-125b transfers beneficial effects on aged cutaneous wound healing.

Aged skin wounds heal poorly, resulting in medical, economic, and social burdens posed by nonhealing wounds. Age-related defects in repair are associated with reduced myofibroblasts and dysfunctional extracellular matrix (ECM) deposition. Bidirectional cell-cell communication involving exosome-borne cargo such as micro RNAs (miRs) has emerged as a critical mechanism for wound healing and aged tissue regeneration. Here we report that at the wound edge, aged fibroblasts display reduced migration and differentiation into myofibroblasts, with impaired ECM deposition, when compared with young tissue. Proper activation of fibroblasts to myofibroblasts may alleviate age-related defects in wound healing. Herein, an exosome-guided cell technique was performed to induce effective wound healing. Supplementing wounds with exosomes isolated from young mouse wound-edge fibroblasts (exosomesYoung) significantly improved the abundance of myofibroblasts and wound healing in aged mice and caused fibroblasts to migrate and transition to myofibroblasts in vitro. To determine the underlying mechanism, we found that exosomal transfer of miR-125b to fibroblasts inhibited sirtuin 7 (Sirt7), thus accelerating myofibroblast differentiation and wound healing in aged mice. Notably, after epidermal inhibition of miR-125b or overexpression of Sirt7 in fibroblasts, migration and myofibroblast transition were perturbed. Our findings thus reveal that miR-125b is transferred through exosomes from young fibroblasts to old fibroblasts contributes to promoting fibroblast migration and transition to counteract aging, suggesting a potential avenue for anti-aging interventions in wound healing.

Analysis of pathogenic factors of Candida albicans and the effect of vaginal immunization on recurrent vulvovaginal candidiasis in mice.

BACKGROUND: The role of fungal pathogenic factors and the immune response of the vaginal epithelium in vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are still unclear. Our study wants to clarify whether there are differences in pathogenic factors between VVC and RVVC strains, confirm the roles of pathogenic factors in the pathogenesis of RVVC, and analyze the influence of pathogenic factors on vaginal host immunity. METHODS: VVC- and RVVC-causing Candida albicans strains were genotyped with 25S rDNA. Drug susceptibility assays using a modified alamarBlue broth microdilution method were carried out. Milk culture medium and egg yolk culture medium were used to measure the secreted aspartate protease (Sap) and phospholipase (Plb) activity of the samples. We used C. albicans with different Sap activity levels to induce RVVC in mice and measured interleukin 4 (IL4), interleukin 8 (IL8), and interleukin 17 (IL17) in vaginal lavage fluid at different stages of RVVC infection. RESULTS: There were no significant differences between VVC and RVVC fungi except that the Sap activity was lower for RVVC-causing C. albicans than for VVC-causing C. albicans. C. albicans with both strong Sap and weak Sap induced RVVC in mice. C. albicans with strong Sap had a reduced RVVC infection rate. In addition, C. albicans with strong Sap stimulated the vaginal epithelium to secrete more IL4, IL8, and IL17. CONCLUSION: Compared with that of VVC-causing C. albicans, the Sap activity of RVVC-causing C. albicans was lower. C. albicans with strong Sap was less capable of causing repeated vaginal infections than that with weak Sap and stimulated the vaginal epithelium to produce more cytokines.

Measuring Beijing's international air connectivity and suggestions for improvement post COVID-19.

This study empirically measures Beijing's international air connectivity through descriptive statistics and various connectivity indexes. In particular, we comprehensively benchmark Beijing's international air connectivity with other major international exchange centers and gateway airports around the world. It is found that, although Beijing has direct flights to a comparable number of foreign destinations, the city still significantly lags behind other major counterparts in international air connectivity. This is due to Beijing's inferior connection quality in terms of flight frequency, number of seats, flying distance, and its poor international transfer capability. Moreover, a gravity-type model is applied to investigate the determinants of Beijing's route-level direct flight traffic. An index of potential market size is calculated for a sample including candidate overseas airports without direct flights with Beijing. It is found that Beijing has already opened direct flights to most of the candidate airports that have high market potentials. The air transport market potentials to major B&R (Belt-and-Road) cities are very low. However, given China's growing trade and economic ties with the B&R countries, Beijing could consider more favorable policies in support of direct flight operations to B&R countries. It is more important for Beijing to upgrade air connectivity quality by liberalizing restrictions on flight frequency and airfare. The newly opened Beijing Daxing Airport adds valuable capacity for Beijing to better explore international connectivity. Although COVID-19 pandemic forces Beijing to shut down international flight operations until now, the city needs to formulate clearer long-term strategies to improve international its air connectivity.

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway.

Many factors are involved in the process of nerve regeneration. Understanding the mechanisms regarding how these factors promote an efficient remyelination is crucial to deciphering the molecular and cellular processes required to promote nerve repair. Schwann cells (SCs) play a central role in the process of peripheral nerve repair/regeneration. Using a model of facial nerve crush injury and repair, we identified Annexin A1 (ANXA1) as the extracellular trigger of SC proliferation and migration. ANXA1 activated formyl peptide receptor 2 (FPR2) receptors and the downstream adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling cascade, leading to SC proliferation and migration in vitro. SCs lacking FPR2 or AMPK displayed a defect in proliferation and migration. After facial nerve injury (FNI), ANXA1 promoted the proliferation of SCs and nerve regeneration in vivo. Collectively, these data identified the ANXA1/FPR2/AMPK axis as an important pathway in SC proliferation and migration. ANXA1-induced remyelination and SC proliferation promotes FNI regeneration.

A systematic review of TMS and neurophysiological biometrics in patients with schizophrenia.

BACKGROUND: Transcranial magnetic stimulation can be combined with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) to evaluate the excitatory and inhibitory functions of the cerebral cortex in a standardized manner. It has been postulated that schizophrenia is a disorder of functional neural connectivity underpinned by a relative imbalance of excitation and inhibition. The aim of this review was to provide a comprehensive overview of TMS-EMG and TMS-EEG research in schizophrenia, focused on excitation or inhibition, connectivity, motor cortical plasticity and the effect of antipsychotic medications, symptom severity and illness duration on TMS-EMG and TMS-EEG indices. METHODS: We searched PsycINFO, Embase and Medline, from database inception to April 2020, for studies that included TMS outcomes in patients with schizophrenia. We used the following combination of search terms: transcranial magnetic stimulation OR tms AND interneurons OR glutamic acid OR gamma aminobutyric acid OR neural inhibition OR pyramidal neurons OR excita* OR inhibit* OR GABA* OR glutam* OR E-I balance OR excitation-inhibition balance AND schizoaffective disorder* OR Schizophrenia OR schizophreni*. RESULTS: TMS-EMG and TMS-EEG measurements revealed deficits in excitation or inhibition, functional connectivity and motor cortical plasticity in patients with schizophrenia. Increased duration of the cortical silent period (a TMS-EMG marker of γ-aminobutyric acid B receptor activity) with clozapine was a relatively consistent finding. LIMITATIONS: Most of the studies used patients with chronic schizophrenia and medicated patients, employed cross-sectional group comparisons and had small sample sizes. CONCLUSION: TMS-EMG and TMS-EEG offer an opportunity to develop a novel and improved understanding of the physiologic processes that underlie schizophrenia and to assess the therapeutic effect of antipsychotic medications. In the future, these techniques may also help predict disease progression and further our understanding of the excitatory/inhibitory balance and its implications for mechanisms that underlie treatment-resistant schizophrenia.

Cardiac ß-adrenergic receptor activation mediates distinct and cell type-dependent changes in the expression and distribution of connexin 43.

Activation of the sympatho-ß-adrenergic receptors (ß-ARs) system is a hallmark of heart failure, leading to fibrosis and arrhythmias. Connexin 43 (Cx43) is the most abundant gap junctional protein in the myocardium. Current knowledge is limited regarding Cx43 remodelling in diverse cell types in the diseased myocardium and the underlying mechanism. We studied cell type-dependent changes in Cx43 remodelling due to ß-AR overactivation and molecular mechanisms involved. Mouse models of isoproterenol stimulation or transgenic cardiomyocyte overexpression of ß2 -AR were used, which exhibited cardiac fibrosis and up-regulated total Cx43 abundance. In both models, whereas Cx43 expression in cardiomyocytes was reduced and more laterally distributed, fibroblasts exhibited elevated Cx43 expression and enhanced gap junction communication. Mechanistically, activation of ß2 -AR in fibroblasts in vitro elevated Cx43 expression, which was abolished by the ß2 -antagonist ICI-118551 or protein kinase A inhibitor H-89, but simulated by the adenylyl cyclase activator forskolin. Our in vitro and in vivo data showed that ß-AR activation-induced production of IL-18 sequentially stimulated Cx43 expression in fibroblasts in a paracrine fashion. In summary, our findings demonstrate a pivotal role of ß-AR in mediating distinct and cell type-dependent changes in the expression and distribution of Cx43, leading to pathological gap junction remodelling in the myocardium.

Overexpression of Foxc1 regenerates crushed rat facial nerves by promoting Schwann cells migration via the Wnt/ß-catenin signaling pathway.

Facial paralysis can result in severe implications for patients. A good prognosis depends on the degree of nerve regeneration. Schwann cells (SCs) play an important role in facial nerve development and regeneration through migration. Forkhead box C1 (Foxc1), a member of the forkhead transcription factor family, is implicated in cell migration. However, the role of Foxc1 in the progression after facial nerve crush remains unknown. Our aim was to evaluate the effect of Foxc1 overexpression on SC migration and recovery of facial nerves after crush injury. The rat facial nerve crush injury model was established through the use of unilateral surgery. The results showed that the expression of Foxc1 was increased in the surgery group compared to that of the control group. SCs were isolated from the sciatic nerves and cultured. Foxc1, delivered by an adeno-associated virus in vivo, or adenovirus in vitro, both induced overexpression of Foxc1, and increased the expression of CXCL12 and ß-catenin. After the transfection of Foxc1, the migration of SC was increased both in vitro and in vivo, was reduced by the inhibition of CXCL12 or ß-catenin. The facial nerve function and the nerve axon remyelination of the rats transfected with Foxc1 were significantly improved after nerve crush injury. Overall, the results demonstrated that overexpression of Foxc1 promoted SC migration by regulating CXCL12 via the Wnt/ß-catenin pathway, thus contributing to improved facial nerve function after crush injury.

Phenological variation of flower longevity and duration of sex phases in a protandrous alpine plant: potential causes and fitness significance.

BACKGROUND: Flower longevity plays an important role in pollen dispersal and reproductive success in plants. In dichogamous plants, the duration of anthesis as well as the time allocated to male and female functions can vary in response to intrinsic factors (e.g., flowering time and resource allocation) and pollination context along a growth season. However, the fitness consequences of phenological dynamics have rarely been examined. This study aims to unravel the potential causes driving variation in flower longevity, duration of sex phases, and phenotypic sex during a flowering season of strongly protandrous Aconitum gymnandrum, and particularly reproductive consequences of the phenological pattern. RESULTS: Population floral sex ratio shifted from completely male at the beginning to completely female at the end of the season, as is common in other protandrous plants. Phenological dynamics of the floral sex ratio and the duration of sex phases caused a shift from femaleness to maleness in the mean phenotypic sex over the whole season. Floral longevity was negatively correlated with flower size and positively affected by temperature. Early flowers within inflorescences rather than early-flowering individuals emphasized the duration of female over male phase. Owing to the dominance of male-phase flowers, early flowering for individual flowers and plants, or female-biased sex resulted in higher pollen deposition per flower and seed set. At the flower level, flower longevity positively affected female reproductive success, while the effect of flower size was negative. By contrast, plant-level female reproductive success was negatively affected by flower longevity but positively correlated to flower size. CONCLUSIONS: The major result of this study lies in elucidating the relationship between variation in phenological sex expression and floral longevity and their fitness consequences of protandrous A. gymnandrum. The contrasting results on female fitness for individual flowers and plants contribute to our current understanding of the adaptive significance of floral longevity.

Development of genomic microsatellite markers for Aconitum gymnandrum (Ranunculaceae) by next generation sequencing (NGS).

Mating plays key roles in the demographic and genetic dynamics of populations. Estimates of mating portfolios and system based on progeny array (PA) method required highly polymorphic genetic markers, of which microsatellite is a good choice. In this study, we reported 19 polymorphic microsatellite loci for Aconitum gymnandrum. The number of alleles per locus ranged from 2 to 12. Observed and expected heterozygosity ranged from 0.000 to 1.000 and from 0.219 to 0.842, respectively. Seven loci showed significant deviation from Hardy-Weinberg equilibrium. These markers will provide a useful tool for pollination ecology and population genetic studies of A. gymnandrum in Qinghai-Tibet plateau.

Exosomal LncRNA-NEAT1 derived from MIF-treated mesenchymal stem cells protected against doxorubicin-induced cardiac senescence through sponging miR-221-3p.

BACKGROUND: The chemotherapy drug doxorubicin (Dox) is widely used for treating a variety of cancers. However, its high cardiotoxicity hampered its clinical use. Exosomes derived from stem cells showed a therapeutic effect against Dox-induced cardiomyopathy (DIC). Previous studies reported that exosomes derived from mesenchymal stem cells (MSCs) pretreated with macrophage migration inhibitory factor (MIF) (exosomeMIF) showed a cardioprotective effect through modulating long noncoding RNAs/microRNAs (lncRNAs/miRs). This study aimed to investigate the role of exosomeMIF in the treatment of DIC. RESULTS: Exosomes were isolated from control MSCs (exosome) and MIF-pretreated MSCs (exosomeMIF). Regulatory lncRNAs activated by MIF pretreatment were explored using genomics approaches. Fluorescence-labeled exosomes were tracked in vitro by fluorescence imaging. In vivo and in vitro, miR-221-3p mimic transfection enforced miR-221-3p overexpression, and senescence-associated ß-galactosidase assay was applied to test cellular senescence. Exosomal delivering LncRNA-NEAT1 induced therapeutic effect in vivo was confirmed by echocardiography. It demonstrated that exosomesMIF recovered the cardiac function and exerted the anti-senescent effect through LncRNA-NEAT1 transfer against Dox. TargetScan and luciferase assay showed that miR-221-3p targeted the Sirt2 3'-untranslated region. Silencing LncRNA-NEAT1 in MSCs, miR-221-3p overexpression or Sirt2 silencing in cardiomyocytes decreased the exosomeMIF-induced anti-senescent effect against Dox. CONCLUSIONS: The results indicated exosomeMIF serving as a promising anti-senescent effector against Dox-induced cardiotoxicity through LncRNA-NEAT1 transfer, thus inhibiting miR-221-3p and leading to Sirt2 activation. The study proposed that exosomeMIF might have the potential to serve as a cardioprotective therapeutic agent during cancer chemotherapy.

Downregulated NOX4 underlies a novel inhibitory role of microRNA-137 in prostate cancer.

Prostate cancer is the second highest caused by cancer-related death among males. microRNAs (miRs) have been reported to participate in carcinogenesis, yet their roles in prostate cancer are rarely studied or investigated. Therefore, the present study attempted to explore the effect of miR-137 in prostate cancer via regulating NADPH oxidase 4 (NOX4). Initially, microarray analysis was performed to obtain prostate cancer-related differentially expressed genes and miRs that regulated NOX4, followed by detecting the expression of miR-137 and NOX4 and its target relationship. Moreover, PC-3 cells were transfected with small interfering RNA (siNOX4) and miR-137 mimic for exploring the effect of miR-137 on glycolysis, cell proliferation, and apoptosis in prostate cancer by evaluating lactate production, glucose uptake, adenosine triphosphate (ATP) production, viability rate, and expression of cleaved caspases 3, 8, and 9, cytochrome c, cleaved poly ADP ribose polymerase (PARP), Bax, and Bcl-2. miR-137 was vital to prostate cancer progression via regulating NOX4. Besides, miR-137 expressed poorly while NOX4 expressed highly in prostate cancer. NOX4 was the target gene of miR-137. Additionally, overexpression of miR-137 and silencing of NOX4 were observed to decrease NOX4 and Bcl-2 protein expression, but increase cleaved caspases 3, 8, and 9, cytochrome c, cleaved-PARP, and Bax protein expression. Furthermore, miR-137 overexpression and NOX4 silencing contributed to decreased lactate production, glucose uptake, ATP production, and cell proliferation, but increased apoptosis rate. Collectively, the present study showed that miR-137 repressed glycolysis in prostate cancer through knockdown of NOX4, which might be a potential theoretical target for prostate cancer treatment.

The effect of quorum sensing on performance of salt-tolerance aerobic granular sludge: linking extracellular polymeric substances and microbial community.

Aerobic granular sludge (AGS) technology is generally negatively affected by the salinity in high saline organic wastewater. The effect of salinity on organic pollutants removal of AGS was studied in three parallel sequencing batch reactors. The results indicated that the performance of reactors operating at relative low salinity (1%) remained stable. However, at medium salinity (2%) and higher salinity (4%) conditions, the organic pollutants removal efficiencies deteriorated from 93.7 ± 3.0 to 71.6 ± 6.8 and 53.6 ± 5.4%, respectively. The addition of a mixture of acyl-homoserine lactone (AHL) mediated quorum sensing (QS) signaling molecules (0.1 µmol/L of mixed C6-HSL, C8-HSL and 3OC8-HSL) only restored the performance of the 2% salinity reactor back to 86.3 ± 6.2% due to the changing of hydrophobic extracellular polymeric substance ratio from 64 ± 3 to 71 ± 4%. Addition of the AHL had no effect on the pollution removal efficiency at the 4% salinity conditions. Microbial community analysis showed that Dyella (32.3%) species were the dominant member of the community and its occurrence was positively correlated with organic pollutants removal efficiency at relative high salinity (2% and 4%), while Mangrovibacter showed the opposite trend. Higher abundances of hdtS and acylase genes, the synthesis and degradation genes of AHL, were found after adding AHLs to reactors at 2% salinity, which indicated that AHL mediated QS was the primary QS system in salt-tolerant AGS.

Enhanced adsorption of Zn2+ by salinity-aided aerobic granular sludge: Performance and binding mechanism.

Aerobic granular sludge (AGS), which is formed by closely associating microorganisms through the production of extracellular polymeric substances (EPS), has proved to be an excellent and promising biosorbent. The reutilization of excess AGS as a kind of biosorbent would be an environmental-friendly means for heavy metal removal and reutilization of excess AGS. In this study, short-term exposure experiments were conducted to determine whether salinity (NaCl concentration ranged from 0 to 50 g/L) caused positive effects on Zn2+ adsorption performance by AGS. The results showed that the AGS formed in response to a 30 g/L saline treatment exhibited the best adsorption performance. Compared with the control (salinity of 0 g/L), the adsorptive capacity at equilibrium increased by 19.90% and reached 29.76 mg/g. The calculated maximum adsorption capacity in 30 g/L saline treatment group was 73.94 mg/g which was higher than described in previous studies using biochar, clarified sludge and aerobic granules. Analysis of EPS components suggested the enhanced adsorption of AGS might be ascribed to increasing polysaccharides content in the EPS after saline treatments. Additionally, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) results indicated hydroxyl groups of EPS played an important role in Zn2+ binding. These findings provide further insight into the application of AGS for heavy metal adsorption.

Third-harmonic generation and scattering in combustion flames using a femtosecond laser filament.

Coherent radiation in the ultraviolent (UV) range has high potential applicability to the diagnosis of the formation processes of soot in combustion because of the high scattering efficiency in the UV wavelength region, even though the UV light is lost largely by the absorption within the combustion flames. We show that the third harmonic (TH) of a Ti:sapphire 800 nm femtosecond laser is generated in a laser-induced filament in a combustion flame and that the conversion efficiency of the TH varies sensitively by the ellipticity of the driver laser pulse but does not vary so much by the choice of alkanol species introduced as fuel for the combustion flames. We also find that the TH recorded from the side direction of the filament is the Rayleigh scattering of the TH by soot nanoparticles within the flame and that the intensity of the TH varies depending on the fuel species as well as on the position of the laser filament within the flame. Our results show that a remote and in situ measurement of distributions of soot nanoparticles in a combustion flame can be achieved by Rayleigh scattering spectroscopy of the TH generated by a femtosecond-laser-induced filament in the combustion flame.