Effect of plasma exosome lncRNA on isoproterenol hydrochloride-induced cardiotoxicity in rats.

Isoprenaline hydrochloride (IH) is a ß-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague-Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through spliceosomes, participate in sphingolipid metabolic pathways, and play a certain role in the circulatory system. Finally, we obtained 3 upregulated lncRNAs through reverse transcription-quantitative PCR (RT-qPCR) verification and selected target lncRNA-mRNA pairs according to the regulatory relationship of lncRNA/mRNA, some of which were associated with myocardial injury. This study provides valuable insights into the role of lncRNAs as novel biomarkers of chemical-induced cardiotoxicity.

Exosomes derived from human umbilical cord mesenchymal stem cells decrease neuroinflammation and facilitate the restoration of nerve function in rats suffering from intracerebral hemorrhage.

Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-ex) have become a hopeful substitute for whole-cell therapy due to their minimal immunogenicity and tumorigenicity. The present study aimed to investigate the hypothesis that hUCMSC-ex can alleviate excessive inflammation resulting from intracerebral hemorrhage (ICH) and facilitate the rehabilitation of the nervous system in rats. In vivo, hemorrhagic stroke was induced by injecting collagenase IV into the striatum of rats using stereotactic techniques. hUCMSC-ex were injected via the tail vein at 6 h after ICH model establishment at a dosage of 200 µg. In vitro, astrocytes were pretreated with hUCMSC-ex and then stimulated with hemin (20 µmol/mL) to establish an ICH cell model. The expression of TLR4/NF-κB signaling pathway proteins and inflammatory factors, including TNF-α, IL-1ß, and IL-10, was assessed both in vivo and in vitro to investigate the impact of hUCMSC-ex on inflammation. The neurological function of the ICH rats was evaluated using the corner turn test, forelimb placement test, Longa score, and Bederson score on the 1st, 3rd, and 5th day. Additionally, RT-PCR was employed to examine the mRNA expression of TLR4 following hUCMSC-ex treatment. The findings demonstrated that hUCMSC-ex downregulated the protein expression of TLR4, NF-κB/P65, and p-P65, reduced the levels of pro-inflammatory cytokines TNF-α and IL-1ß, and increased the expression of the anti-inflammatory cytokine IL-10. Ultimately, the administration of hUCMSC-ex improved the behavioral performance of the ICH rats. However, the results of PT-PCR indicated that hUCMSC-ex did not affect the expression of TLR4 mRNA induced by ICH, suggesting that hUCMSCs-ex may inhibit TLR4 translation rather than transcription, thereby suppressing the TLR4/NF-κB signaling pathway. We can conclude that hUCMSC-ex mitigates hyperinflammation following ICH by inhibiting the TLR4/NF-κB signaling pathway. This study provides preclinical evidence for the potential future application of hUCMSC-ex in the treatment of cerebral injury.

Regiodivergent and Stereoselective Synthesis of Highly Substituted 1,3-Dienes via Arylative Acyloxy Migration of Propargyl Esters.

We report the first catalyst-controlled regiodivergent method that enables the synthesis of structurally diverse 1,2,3,4-tetrasubstituted conjugated dienes with excellent regio- and stereochemical outcomes from the same set of readily available propargyl esters and diaryliodonium salts. In this diene chemistry, the in situ generated, highly electrophilic aryl-CuIII complex serves not only as a π-Lewis acid catalyst for alkyne activation/acyloxy migration but also as an aryl electrophile equivalent. The competitive arylative 1,2- and 1,3-acyloxy migration patterns are exquisitely dictated by Cu and Au/Cu relay catalyses, respectively, providing a modular and attractive approach to traditionally inaccessible tetrasubstituted 1,3-dienes in a regiodivergent manner. Finally, the synthetic utility of this method is demonstrated by further synthetic derivatization of 1,3-dienes into an array of useful compounds.

Transcriptome Analysis and VIGS Identification of Key Genes Regulating Citric Acid Metabolism in Citrus.

Citrus (Citrus reticulata) is one of the world's most widely planted and highest-yielding fruit trees. Citrus fruits are rich in a variety of nutrients. The content of citric acid plays a decisive role in the flavor quality of the fruit. There is a high organic acid content in early-maturing and extra-precocious citrus varieties. Reducing the amount of organic acid after fruit ripening is significant to the citrus industry. In this study, we selected a low-acid variety, "DF4", and a high-acid variety, "WZ", as research materials. Through WGCNA analysis, two differentially expressed genes, citrate synthase (CS) and ATP citrate-pro-S-lyase (ACL), were screened out, which related to the changing citric acid. The two differentially expressed genes were preliminarily verified by constructing a virus-induced gene-silencing (VIGS) vector. The VIGS results showed that the citric acid content was negatively correlated with CS expression and positively correlated with ACL expression, while CS and ACL oppositely control citric acid and inversely regulate each other. These results provide a theoretical basis for promoting the breeding of early-maturing and low-acid citrus varieties.

Effective protection: the embryonic development and clinical outcomes of emergency vitrification of 1246 oocytes and Day 0-Day 5 embryos in a natural disaster.

STUDY QUESTION: Can emergency vitrification protect embryos and oocytes during natural disasters or other events that prevent normal practice to achieve satisfactory embryonic development and clinical outcomes at a later time? SUMMARY ANSWER: Emergency vitrification of oocytes and Day 0-Day 5 (D0-D5) embryos during disasters is a safe and effective protective measure. WHAT IS KNOWN ALREADY: When some destructive events such as floods, earthquakes, tsunamis, and other accidents occur, emergency vitrification in embryo laboratories to protect human embryos, oocytes, and sperm is one of the important measures of an IVF emergency plan. However, there are few detailed reports on emergency vitrification in a state of disaster, especially about oocytes and D0 zygotes. Therefore, the effectiveness and safety of emergency vitrification of oocytes and D0-D5 embryos in disaster states are still unclear. STUDY DESIGN, SIZE, DURATION: A retrospective study was made in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2018 to November 2022. The record rainstorms in Zhengzhou, China, caused severe flooding, traffic disruptions, and power outages. From 17:30, 20 July 2021 to 17:30, 21 July 2021, 1246 oocytes and D0-D5 embryos of 155 patients were vitrified whilst the laboratory had only an emergency power supply. PARTICIPANTS/MATERIALS, SETTING, METHODS: As of 21 December 2021, 1149 emergency vitrified oocytes and D0-D5 embryos of 124 patients underwent frozen-thawed embryo transfer (FET). They were divided into the following four groups according to the days of embryo culture in vitro: oocyte group, Day 0-Day 1 (D0-D1) group, Day 2-Day 3 (D2-D3) group, and Day 4-Day 5 (D4-D5) group. Control groups for each were selected from fresh cycle patients who underwent IVF/ICSI from January 2018 to October 2021. Control and emergency vitrification patients were matched on criteria that included age, fertilization method, days of embryonic development, and number and grade of transferred embryos. A total of 493 control patients were randomly selected from the eligible patients and matched with the emergency vitrification groups in a ratio of 4:1. The results of assisted reproduction and follow-up of pregnancy were analyzed. The embryonic development, clinical outcomes, and birth outcomes in each group were statistically analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: A significant difference was observed in fertilization rate (81% versus 72%, P = 0.022) between the oocyte group and the control group. Significant differences were also observed in the monozygotic twin pregnancy rate (10% versus 0%, P = 0.038) and ectopic pregnancy rate (5% versus 0%, P = 0.039) between the D0-D1 group and the control group. No significant differences (P > 0.05) were observed between vitrified oocytes/D0-D1 embryos/D2-D3 embryos and the control group on the number of high-quality embryos (3.17 ± 3.00 versus 3.84 ± 3.01, P = 0.346; 5.04 ± 3.66 versus 4.56 ± 2.87, P = 0.346; 4.85 ± 5.36 versus 5.04 ± 4.64, P = 0.839), the number of usable blastocysts (1.22 ± 1.78 versus 1.21 ± 2.03, P = 0.981; 2.16 ± 2.26 versus 1.55 ± 2.08, P = 0.090; 2.82 ± 3.23 versus 2.58 ± 3.32, P = 0.706), clinical pregnancy rate (56% versus 57%, P = 0.915; 55% versus 55%, P = 1.000; 40% versus 50%, P = 0.488), miscarriage rate (30% versus 15%, P = 0.496; 5% versus 11%, P = 0.678; 17% versus 20%, P = 1.000), and live birth rate (39% versus 49%, P = 0.460; 53% versus 50%, P = 0.772; 33% versus 40%, P = 0.635). No significant differences (P > 0.05) were observed between the D4-D5 group and the control group on clinical pregnancy rate (40% versus 55%, P = 0.645), miscarriage rate (0% versus 18%, P = 1.000), and live birth rate (40% versus 45%, P = 1.000). LIMITATIONS, REASONS FOR CAUTION: The retrospective study design is a limitation. The timing and extent of natural disasters are unpredictable, so the sample size of vitrified oocytes, zygotes, and embryos is beyond experimental control. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first study analyzing embryonic development, clinical outcomes, and birth outcomes of large samples of oocytes, D0 zygotes, and D1-D5 embryos after emergency vitrification under the disaster conditions. The results show that emergency vitrification is a safe and effective protective measure applicable to oocytes and D0-D5 embryos. The embryology laboratories need to be equipped with an emergency uninterrupted power supply capable of delivering for 6-8 h at full load. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (grant 81871206). The authors declare that they have no conflicts of interest. All authors have completed the ICMJE Disclosure form. TRIAL REGISTRATION NUMBER: N/A.

Gabapentin Alleviates Brain Injury in Intracerebral Hemorrhage Through Suppressing Neuroinflammation and Apoptosis.

Neuroinflammation plays an important role in brain tissue injury during intracerebral hemorrhage. Gabapentin can reduce inflammation and oxidative stress through inhibiting nuclear factor κB (NFκB) signals. Here, we showed that gabapentin reduced brain tissue injury in ICH through suppressing NFκB-mediated neuroinflammation. ICH was induced by injecting collagenase IV into the right striatum of Sprague-Dawley rats. PC12 and BV2 cells injury induced by Hemin were used to simulate ICH in vitro. Inflammation and apoptosis were assessed in rat brain tissue and in vitro cells. The neurobehavioral scores were significantly decreased in ICH rats compared with sham rats. Phosphorylated IκB-α and cleaved caspase3, and apoptosis rate were significantly higher in tissue surrounding the hematoma than in brain tissues from rats subjected to sham surgery. Furthermore, serum IL-6 levels in ICH rats were higher than in sham rats. Gabapentin treatment significantly improved the behavioral scores, decreased levels of phosphorylated IκB-α and cleaved caspase3, apoptosis rate, and serum IL-6 level in ICH rats. Hemin-treated BV2 cells displayed higher levels of phosphorylated IκB-α, cleaved caspase3, and IL-6 in the supernatant compared with vehicle-treated cells. Hemin treatment induced a significantly lower level of peroxisome proliferator-activated receptor γ (PPARγ) in BV2 cells. BV2-PC12 co-culture cells treated by hemin displayed higher levels of cleaved caspase3 in PC12 cells. Furthermore, gabapentin treatment could reduce these effects induced by hemin and the protective effects of gabapentin were significantly attenuated by PPARγ inhibitor. Therefore, gabapentin may reduce inflammation and apoptosis induced by the ICH through PPARγ-NFκB pathway.

Sesamol Augments Paclitaxel-Induced Apoptosis in Human Cervical Cancer Cell Lines.

Natural medicinal compounds have gained increasing attention as adjuvants during cancer chemotherapy. The present study demonstrated the chemosensitizing effect of sesamol, a natural phenolic compound, in HeLa cell lines In Vitro. Sesamol-pretreated (10 µM) HeLa cells were exposed to 7.5 nM paclitaxel. The chemosensitization was estimated by MTT-based metabolic assay. Further, oxidative DNA damage, alterations in mitochondrial membrane potential (MMP), and apoptotic morphological changes were analyzed. Sesamol treatment before paclitaxel treatment significantly decreased the IC50 value of paclitaxel (7.5 nM) in a concentration-dependent manner. Further, Sesamol treatment before paclitaxel increased the intracellular ROS levels and enhanced apoptosis through MMP alterations. Moreover, there was an increased % of tail DNA in sesamol + paclitaxel-treated cervical cancer cells compared to paclitaxel alone treatment. The frequency of apoptotic cells were also increased during sesamol + paclitaxel treatment cells compared to paclitaxel alone treatment. Thus, Sesamol treatment before paclitaxel exposure enhanced the apoptotic cell death in the HeLa cell lines. The results of the present study were in support of the usage of natural medicinal compounds for clinical chemotherapy after systematic animal experimentations.

Palladium-Catalyzed Regiodivergent Synthesis of 1,3-Dienyl and Allyl Esters from Propargyl Esters.

Catalyst-controlled regiodivergent catalysis is a vital chemical tool that allows efficient access to large collections of structurally diverse molecules from a common precursor but remains a challenge. We report a catalyst-controlled, tunable, and predictable regiodivergency in transforming the internal aliphatic propargyl esters into diverse libraries of highly substituted 1,3-dienyl and allyl products by Pd-catalysis. Depending on the ligand employed, the palladium catalyst can involve two typical approaches: electrophilic palladium catalysis and a sequential oxidative addition-reductive elimination pathway. This regiodivergent protocol endows facile access to four regioisomers with high regio- and stereoselectivity from the common propargyl esters. In terms of synthetic utility, a notable feature of this protocol is amenable to structural diversification of bioactive relevant molecules, enabling rapid assembly of many useful structural analogs of pharmaceutical candidates.

The Unusual Photochromic and Hydrochromic Switching Behavior of Cellulose-Embedded 1,8-Naphthalimide-Viologen Derivatives in the Solid-State.

Stimuli-responsive chromic materials such as photochromics, hydrochromics, thermochromics, and electrochromics have a long history of capturing the attention of scientists due to their potential industrial applications and novelty in popular culture. However, hybrid chromic materials that combine two or more stimuli-triggered color changing properties are not so well known. Herein, we report a design strategy that has led to a series of emissive 1,8-naphthalimide-viologen dyads which exhibit unusual dual photochromic and hydrochromic switching behavior in the solid-state when embedded in a cellulose matrix. This behavior manifests as reversible solid state fluorescence hydrochromism upon changes in atmospheric relative humidity (RH), and reversible solid state photochromism upon generation of a cellulose-stabilized viologen radical cation. In this design strategy, the bipyridinium unit serves as both a water-sensitive receptor for the hydrochromic fluorophore-receptor system, and a photochromic group, capable of eliciting its own visible colorimetric response, generating a fluorescence quenching radical cation with prolonged exposure to ultraviolet (UV) light. These dyes can be inkjet-printed onto cellulose paper or drop-cast as cellulose powder-based films and can be unidirectionally cycled between three different states which can be characteristically visualized under UV light or visible light. The material's photochromism, hydrochromism, and underlying mechanism of action was investigated using computational analysis, dynamic vapor sorption/desorption isotherms, electron paramagnetic resonance spectroscopy, and variable humidity UV-Vis adsorption and fluorescence spectroscopies.

Halogen-modified carbazole derivatives for lipid droplet-specific bioimaging and two-photon photodynamic therapy.

Lipid droplets (LDs) are dynamic multifunctional organelles that participate in the regulation of many metabolic processes, visualization of which is necessary for biological research. In this work, a series of two-photon responsive fluorescent probes (C-H, C-Br, and C-I) based on carbazole units were designed and synthesized. Thereinto, an iodine-modified carbazole derivative C-I exhibited an exciting lipid droplet targeting ability due to its excellent lipophilicity. Meanwhile, benefiting from its larger Stokes shift and two-photon absorption cross-section, C-I was employed for two-photon confocal laser scanning microscopy (CLSM) and stimulated emission depletion (STED) microscopy imaging to observe LDs more accurately. In addition, given the heavy atom effect, C-I can effectively generate reactive oxygen species (ROS) leading to cancer cell apoptosis under near-infrared light irradiation. Notably, we explained the process of cell apoptosis through in vitro simulation experiments. This study provides a promising platform for visualization of lipid droplets.

Factors impacting cumulative dissipated energy levels and postoperative visual acuity outcome in cataract surgery.

PURPOSE: To determine factors impacting cumulative dissipated energy (CDE) and postoperative best-corrected visual acuity (BCVA) in phacoemulsification. DESIGN: Review of 1102 cases at University of California, San Francisco (UCSF) and at Zhongshan Ophthalmic Center (ZOC), China. SUBJECTS: Patients who underwent cataract surgery at UCSF 03/2014-03/2019 and at ZOC 10/2018-05/2019. METHODS: Patient demographics, medical history, routine ocular examination, and surgical information, including disassembly method, complications, and surgeon training level were recorded. Univariable and multivariable regression models were used to determine factors associated with CDE and good postoperative BCVA (20/40 or better) at 1 month. OUTCOME MEASURES: CDE, postoperative BCVA. RESULTS: In multivariable analysis, patient age at time of surgery, diabetes, degree of nuclear sclerosis (NS), white-to-white corneal diameter, disassembly method, preoperative BCVA, surgeon training level, and surgical center were significantly associated with CDE. Log10CDE increased by 0.20-0.31 for patient age ≥ 70 years, by 0.07 if the patient had diabetes, by 0.12-0.41 for NS grade ≥ 2, by 0.48 per 10 mm increase in white-to-white corneal diameter, by 0.34-0.47 for disassembly method other than non-stop chop, by 0.16 per unit increase in preoperative logMAR BCVA, and by > 0.09 when phacoemulsification was performed by residents early in their training. Log10CDE was 0.33 higher at UCSF than ZOC. In multivariable analysis, worse baseline visual acuity and age above 90 years at time of surgery decreased the odds of good BCVA (OR = 0.26 per unit increase in preoperative logMAR BCVA; OR = 0.12 for age > 90); comorbid retinal issues decreased the odds of good postoperative BCVA (OR = 0.13-0.39); greater anterior chamber depth (ACD) or shorter axial length (AL), increased the odds of good postoperative outcome (OR = 2.64 per 1 mm increase ACD, OR = 0.84 per 1 mm increase AL). CONCLUSIONS: Cataract grade determined by slit lamp exam and, for the first time, older patient age, were noted to be important predictors of high CDE. CDE was not a risk factor for postoperative BCVA measured at postoperative 1 month. When surgery was performed by trainees under supervision, lower training level was associated with higher CDE, but not with worse postoperative BCVA.

Ambient air pollutant exposure and in vitro fertilization treatment outcomes in Zhengzhou, China.

OBJECTIVE: To study the association between ambient air pollutant exposure during the follicular phase and in vitro fertilization (IVF) outcomes. DESIGN: A single-center retrospective analysis. SETTING: Henan Province, China. PATIENTS: Patients (n = 6659) living in Zhengzhou, Henan Province in central China who underwent their first IVF cycle at the First Affiliated Hospital of Zhengzhou University between 2013 and 2019 were included for analysis. INTERVENTION: None. MAIN OUTCOME MEASURE: The relationships between PM2.5, PM10, and AQI (Air Quality Index) with IVF outcomes during the follicular phase (period I, 85 days before oocyte retrieval; period II, gonadotrophin start to oocyte retrieval). RESULTS: Compared with the bottom tertile, exposure to the top PM2.5 and PM10 tertiles during period I was associated with decreased clinical pregnancy (PM2.5: adjusted odds ratio [OR], 0.838%, and 95% confidence interval [CI], 0.723 and 0.971; PM10: adjusted OR, 0.818%, and 95% CI, 0.705 and 0.950), and decreased live birth rate (PM2.5: adjusted odds ratio [OR], 0.852%, and 95% confidence interval [CI], 0.736 and 0.987; PM10: adjusted OR, 0.850%, and 95% CI, 0.733 and 0.986), and exposure to the top PM2.5 tertile during period II adversely affected clinical pregnancy and the live birth rate (adjusted OR, 0.824%, and 95% CI, 0.711 and 0.955; adjusted OR, 0.817%, and 95% CI, 0.706 and 0.945). Compared with the bottom PM10 tertile, exposure to the middle PM10 tertile in period II showed decreased clinical pregnancies and live births (adjusted OR, 0.844; 95% CI, 0.729 and 0.978, adjusted OR, 0.846; 95% CI, 0.731 and 0.979). The PM10 level during period II of the follicular phase tend to adversely affect live birth rate, but the tendency did not reach significance (P = 0.051). CONCLUSION: Exposure to PM2.5 and PM10 before oocyte retrieval has an adverse effect on IVF outcomes. CAPSULE: Exposure to PM2.5 and PM10 before oocyte retrieval has an adverse effect on IVF outcomes.

Classical and non-classical melatonin receptor agonist-directed micellization of bipyridinium-based supramolecular amphiphiles in water.

The addition of molecular recognition units into structures of amphiphiles is a means by which soft matter capable of undergoing template-directed micellization can be obtained. These supramolecular amphiphiles can bind with molecular templates using non-covalent bonding interactions, forming host-guest complexes that hold the amphiphiles together as they undergo micellization. In most cases, such templates are synthesized and designed for a specific molecular recognition motif. It is not clear, however, to what extent these types of amphiphile systems are responsive to members of a biologically derived class of molecular targets, for example, melatonin receptor agonists and their numerous isosteres. Herein, we describe the template-directed micellization and arrangement at the air-water interface of a bipyridinium-based gemini surfactant, driven by the influence of donor-acceptor CT interactions with a series of bioactive classical and non-classical melatonin isosteres. Under the conditions of templation by either 5-methoxytryptophol, N-acetylserotonin, N-acetyltryptamine, or the pharmaceutical agent agomelatine, favorable Gibbs free energies of micellization were observed with decreases in CMC by up to 70%, and concomitant increases of 28% in surface pressure, and decreases of 20% in contact angle versus untemplated solutions. Solid state thermochromic transition temperatures for inkjet-printed patterns of the templated amphiphile solutions were inversely correlated with trends observed for their respective CMCs, and exhibited no correlation to their binding constants. These findings contend for the generalizable use of melatonin receptor agonists as targets and/or templates for chemical systems, which rely on π-stacking donor-acceptor CT interactions in water to facilitate the actions of binding, sequestration, or template-directed self-assembly.

Hydrogen gas reduces chronic intermittent hypoxia-induced hypertension by inhibiting sympathetic nerve activity and increasing vasodilator responses via the antioxidation.

Molecular hydrogen is reported to be used medically to ameliorate various systemic pathological conditions. This study aimed to investigate the effect of hydrogen (H2 ) gas on hypertension induced by intermittent hypoxia in rats. The adult rats were exposed to chronic intermittent hypoxia (CIH) 8 hours/day for 5 weeks and/or H 2 gas 2 hours/day. We found that the systolic and diastolic blood pressure (BP) increased significantly in rats exposed to intermittent hypoxia, both of which were markedly attenuated after H treatment. Furthermore, intermittent hypoxia exposure elevated renal sympathetic nerve activity, consistent with plasma norepinephrine. Additionally, H 2 gas significantly improved CIH-induced abnormal vascular relaxation. Nevertheless, inhalation of H 2 gas alone did not cause such changes. Moreover, H 2 gas-treated rats exposed to CIH showed a significant reduction in 8-hydroxy-2 deoxyguanosine content and increases in superoxide dismutase activity, indicating improved oxidative stress. Taken together, these results indicate that H 2 gas has significant effects on the reduction of BP without any side effects. Mechanistically, inhibition of sympathetic activity and reduction of systemic vascular resistance may participate in this process via the antioxidant activity of H 2 .

Development of SSR markers via de novo transcriptome assembly in Akebia trifoliata (Thunb.) Koidz.

Owing to its high nutritive, economic, and medicinal values, Akebia trifoliata has received increased attention, making worthy of being used as a new fruit crop for further domestication and commercialization in China. However, molecular research of A. trifoliata has lagged as investigations of its genomic resources and molecular markers are rare. In this study, a cDNA library of A. trifoliata leaves was sequenced using the Illumina NovaSeq. 6000 sequencing system. In total, 101 417 transcripts, 63 757 unigenes, and 9494 simple sequence repeats were assembled and identified from the transcriptome datasets. The majority of the SSRs were di- and trinucleotide repeats. Length and number of SSR motifs ranged from 15 to 66, and 5 to 48 bp, respectively. Of which, the A/T mononucleotide motif and AG/TC and CT/GA dinucleotide motifs were the most abundant. Furthermore, 100 SSR primers were randomly selected to validate amplification and polymorphism, and 88 A. trifoliata accessions were definitively distinguished by 49 primers. With the Qinling mountains and Huaihe River line as the boundaries, the northern and southern accessions were clustered into different groups, but no clear geographical patterns (city or origin) were observed in the southern accessions. These newly identified molecular markers may provide a foundation for the genetic identification and diversity analysis and marker-assisted selection breeding in species of Akebia.

Hydrogen Gas Alleviates Chronic Intermittent Hypoxia-Induced Renal Injury through Reducing Iron Overload.

Iron-induced oxidative stress has been found to be a central player in the pathogenesis of kidney injury. Recent studies have indicated H2 can be used as a novel antioxidant to protect cells. The present study was designed to investigate the protective effects of H2 against chronic intermittent hypoxia (CIH)-induced renal injury and its correlation mechanism involved in iron metabolism. We found that CIH-induced renal iron overloaded along with increased apoptosis and oxidative stress. Iron accumulates mainly occurred in the proximal tubule epithelial cells of rats as showed by Perl's stain. Moreover, we found that CIH could promote renal transferrin receptor and divalent metal transporter-1 expression, inhibit ceruloplasmin expression. Renal injury, apoptosis and oxidative stress induced by CIH were strikingly attenuated in H2 treated rats. In conclusion, hydrogen may attenuate CIH-induced renal injury at least partially via inhibiting renal iron overload.

Assembly and Chiral Memory Effects of Dynamic Macroscopic Supramolecular Helices.

Macroscopic enantiomerically pure helical supramolecular fibers are bottom-up assembled in aqueous media from a chiral π-electron donor template and an achiral π-electron acceptor. The helices can be assembled to the sub-millimeter scale with controlled handedness. These dynamic supramolecular architectures allow for a quantitative exchange of the chiral donor template with achiral analogues. During this process, a chiral memory effect was observed, affording enantiomerically pure helices composed entirely of achiral components.

Melatonin-directed micellization: a case for tryptophan metabolites and their classical bioisosteres as templates for the self-assembly of bipyridinium-based supramolecular amphiphiles in water.

The bulk solution properties of amphiphilic formulations are derivative of their self-assembly into higher ordered supramolecular assemblies known as micelles and of their ordering at the air-water interface. Exerting control over the surface-active properties of amphiphiles and their propensity to aggregate in pure water is most often fine-tuned by covalent modification of their molecular structure. Nevertheless structural constraints which limit the performance of amphiphiles do emerge when trying to develop more sophisticated systems which undergo for example, shape-defined controlled assembly and/or respond to external stimuli. In this regard, the template-modulated assembly of the so-called "supramolecular amphiphiles" continues to make progress ordering molecules that otherwise have very little to no driving force to aggregate in a prescribed manner in aqueous solutions. Herein we describe the template-modulated micellization and ordering at the air-water interface of bipyridinium-based supramolecular amphiphiles triggered by host-guest interactions with high specificity for the neurotransmitter melatonin over its biosynthetic synthon l-tryptophan and the thermodynamic parameters governing the template-modulated micellization process. When bound to the bipyridinium units of micellized surfactant molecules, melatonin effectively serves as "molecular glue" capable of lowering the CMC by 52% as compared to untemplated solutions. Analysis of this system suggests that a hallmark of donor-acceptor template-modulated micellization in water is a strong positively correlated temperature dependence of the CMC and the absence of a U-shaped CMC-temperature curve. Our findings make a case for the incorporation of l-tryptophan-based metabolites and their classical synthetic pharmaceutical bioisosteres as potential targets/components of donor-acceptor CT-based supramolecular amphiphile systems/materials operating in water.

Autophagy inhibits high glucose induced cardiac microvascular endothelial cells apoptosis by mTOR signal pathway.

Cardiac microvascular endothelial cells (CMECs) dysfunction is an important pathophysiological event in the cardiovascular complications induced by diabetes. However, the underlying mechanism is not fully clarified. Autophagy is involved in programmed cell death. Here we investigated the potential role of autophagy on the CMECs injury induced by high glucose. CMECs were cultured in normal or high glucose medium for 6, 12 and 24 h respectively. The autophagy of CMECs was measured by green fluorescence protein (GFP)-LC3 plasmid transfection. Moreover, the apoptosis of CMEC was determined by flow cytometry. Furthermore, 3-Methyladenine (3MA), ATG7 siRNA and rapamycin were administrated to regulate the autophagy state. Moreover, Western blotting assay was performed to measure the expressions of Akt, mTOR, LC3 and p62. High glucose stress decreased the autophagy, whereas increased the apoptosis in CMECs time dependently. Meanwhile, high glucose stress activated the Akt/mTOR signal pathway. Furthermore, autophagy inhibitor, 3-MA and ATG7 siRNA impaired the autophagy and increased the apoptosis in CMECs induced by high glucose stress. Conversely, rapamycin up-regulated the autophagy and decreased the apoptosis in CMECs under high glucose condition. Our data provide evidence that high glucose directly inhibits autophagy, as a beneficial adaptive response to protect CMECs against apoptosis. Furthermore, the autophagy was mediated, at least in part, by mTOR signaling.

Development of a core collection for ramie by heuristic search based on SSR markers.

There are more than 2000 ramie germplasms in the National Ramie Germplasm Nursery affiliated with the Institute of Bast Fiber Crops, Chinese Academy of Agricultural Science, China. As it is difficult to perform effective conservation, management, evaluation, and utilization of redundant genetic resources, it is necessary to construct a core collection by using molecular markers. In this study, a core collection of ramie consisting of 22 germplasms was constructed from 108 accessions by heuristic search based on 21 Simple Sequence Repeat (SSR) marker combinations. The results showed that there is a poor relationship between the core collection and the geographic distribution. The number of amplification bands for the core collection was the same as that for the entire collection. Shannon's index for three of the SSR primers (14%) and Nei's index for nine of the SSR primers (19%) were lower in the core collection than in the entire collection. The true core collection had wider genetic diversity compared with the random core collection. Collectively, the core collection constructed in this study is reliable and represents the genetic diversity of all the 108 accessions.