Hepatic IRE1α-XBP1 signaling promotes GDF15-mediated anorexia and body weight loss in chemotherapy.

Platinum-based chemotherapy drugs can lead to the development of anorexia, a detrimental effect on the overall health of cancer patients. However, managing chemotherapy-induced anorexia and subsequent weight loss remains challenging due to limited effective therapeutic strategies. Growth differentiation factor 15 (GDF15) has recently gained significant attention in the context of chemotherapy-induced anorexia. Here, we report that hepatic GDF15 plays a crucial role in regulating body weight in response to chemo drugs cisplatin and doxorubicin. Cisplatin and doxorubicin treatments induce hepatic Gdf15 expression and elevate circulating GDF15 levels, leading to hunger suppression and subsequent weight loss. Mechanistically, selective activation by chemotherapy of hepatic IRE1α-XBP1 pathway of the unfolded protein response (UPR) upregulates Gdf15 expression. Genetic and pharmacological inactivation of IRE1α is sufficient to ameliorate chemotherapy-induced anorexia and body weight loss. These results identify hepatic IRE1α as a molecular driver of GDF15-mediated anorexia and suggest that blocking IRE1α RNase activity offers a therapeutic strategy to alleviate the adverse anorexia effects in chemotherapy.

Oxytocin, but not vasopressin, decreases willingness to harm others by promoting moral emotions of guilt and shame.

Prosocial and moral behaviors have overlapping neural systems and can both be affected in a number of psychiatric disorders, although whether they involve similar neurochemical systems is unclear. In the current registered randomized placebo-controlled trial on 180 adult male and female subjects, we investigated the effects of intranasal administration of oxytocin and vasopressin, which play key roles in influencing social behavior, on moral emotion ratings for situations involving harming others and on judgments of moral dilemmas where others are harmed for a greater good. Oxytocin, but not vasopressin, enhanced feelings of guilt and shame for intentional but not accidental harm and reduced endorsement of intentionally harming others to achieve a greater good. Neither peptide influenced arousal ratings for the scenarios. Effects of oxytocin on guilt and shame were strongest in individuals scoring lower on the personal distress subscale of trait empathy. Overall, findings demonstrate for the first time that oxytocin, but not vasopressin, promotes enhanced feelings of guilt and shame and unwillingness to harm others irrespective of the consequences. This may reflect associations between oxytocin and empathy and vasopressin with aggression and suggests that oxytocin may have greater therapeutic potential for disorders with atypical social and moral behavior.

In Situ Reduction of Silver Nanoparticles/Urushiol-Based Polybenzoxazine Composite Coatings with Enhanced Antimicrobial and Antifouling Performances.

Marine anti-fouling coatings represent an efficient approach to prevent and control the marine biofouling. However, a significant amount of antifouling agent is added to improve the static antifouling performance of the coatings, which leads to an issue whereby static antifouling performance conflicts with eco-friendly traits. Herein, this work reports an in situ reduction synthesis of silver nanoparticles (AgNPs) within polymers to produce composite coatings, aiming to solve the aforementioned issue. Firstly, urushiol-based benzoxazine monomers were synthesized by the Mannich reaction, using an eco-friendly natural product urushiol and n-octylamine and paraformaldehyde as the reactants. Additionally, AgNPs were obtained through the employment of free radicals formed by phenolic hydroxyl groups in the urushiol-based benzoxazine monomers, achieved by the in situ reduction of silver nitrate in benzoxazine. Then, the urushiol-based benzoxazine/AgNPs composite coatings were prepared by the thermosetting method. AgNPs exhibit broad-spectrum and highly efficient antimicrobial properties, with a low risk to human health and a minimal environmental impact. The composite coating containing a small amount of AgNPs (≤1 wt%) exhibits effective inhibition against various types of bacteria and marine microalgae in static immersion, thereby displaying outstanding antifouling properties. This organic polymer and inorganic nanoparticle composite marine antifouling coating, with its simple preparation method and eco-friendliness, presents an effective solution to the conflict between static antifouling effectiveness and environmental sustainability in marine antifouling coatings.

Patterns of neural activity in response to threatening faces are predictive of autistic traits: modulatory effects of oxytocin receptor genotype.

Autistic individuals generally demonstrate impaired emotion recognition but it is unclear whether effects are emotion-specific or influenced by oxytocin receptor (OXTR) genotype. Here we implemented a dimensional approach using an implicit emotion recognition task together with functional MRI in a large cohort of neurotypical adult participants (N = 255, male = 131, aged 17-29 years) to establish associations between autistic traits and neural and behavioral responses to specific face emotions, together with modulatory effects of OXTR genotype. A searchlight-based multivariate pattern analysis (MVPA) revealed an extensive network of frontal, basal ganglia, cingulate and limbic regions exhibiting significant predictability for autistic traits from patterns of responses to angry relative to neutral expression faces. Functional connectivity analyses revealed a genotype interaction (OXTR SNPs rs2254298, rs2268491) for coupling between the orbitofrontal cortex and mid-cingulate during angry expression processing, with a negative association between coupling and autistic traits in the risk-allele group and a positive one in the non-risk allele group. Overall, results indicate extensive emotion-specific associations primarily between patterns of neural responses to angry faces and autistic traits in regions processing motivation, reward and salience but not in early visual processing. Functional connections between these identified regions were not only associated with autistic traits but also influenced by OXTR genotype. Thus, altered patterns of neural responses to threatening faces may be a potential biomarker for autistic symptoms although modulatory influences of OXTR genotype need to be taken into account.

Designed Synthesis of Fe/Zr Bimetallic Organic Framework to Enhance the Selective Conversion of H2S to Sulfur.

The development of stable and effective catalysts to convert toxic H2S into high value-added sulfur is essential for production safety and environmental protection. However, the inherent defects of traditional iron- and zirconium-based catalysts, such as poor activity, high oxygen consumption, and low sulfur selectivity, limit their further developments and applications. Herein, the Fe-Zr bimetallic organic framework FeUIO-66(x) with different cubic morphologies was synthesized via a facile solvothermal method. The results indicate that the introduction of Fe not only increases the specific surface area and weak L-sites of the catalyst without changing its crystal structure, which provides enough reaction space and more active sites for the adsorption and activation of H2S, but also reduces the activation energy of the reaction, significantly promoting the selective oxidation of H2S. As a result, the as-obtained FeUIO-66(1) catalyst exhibits the highest desulfurization activity and superior durability and water resistance stability, and its H2S conversion and sulfur selectivity within 50 h are 100 and 88%, respectively. More importantly, the structure of the catalyst after the desulfurization reaction is consistent with that of the fresh counterpart. The study offers new insights into the development of effective and stable bimetallic catalysts to eliminate H2S and recycle sulfur.

Prediction of clinical progression in nervous system diseases: plasma glial fibrillary acidic protein (GFAP).

Glial fibrillary acidic protein (GFAP), an intracellular type III intermediate filament protein, provides structural support and maintains the mechanical integrity of astrocytes. It is predominantly found in the astrocytes which are the most abundant subtypes of glial cells in the brain and spinal cord. As a marker protein of astrocytes, GFAP may exert a variety of physiological effects in neurological diseases. For example, previous published literatures showed that autoimmune GFAP astrocytopathy is an inflammatory disease of the central nervous system (CNS). Moreover, the studies of GFAP in brain tumors mainly focus on the predictive value of tumor volume. Furthermore, using biomarkers in the early setting will lead to a simplified and standardized way to estimate the poor outcome in traumatic brain injury (TBI) and ischemic stroke. Recently, observational studies revealed that cerebrospinal fluid (CSF) GFAP, as a valuable potential diagnostic biomarker for neurosyphilis, had a sensitivity of 76.60% and specificity of 85.56%. The reason plasma GFAP could serve as a promising biomarker for diagnosis and prediction of Alzheimer's disease (AD) is that it effectively distinguished AD dementia from multiple neurodegenerative diseases and predicted the individual risk of AD progression. In addition, GFAP can be helpful in differentiating relapsing-remitting multiple sclerosis (RRMS) versus progressive MS (PMS). This review article aims to provide an overview of GFAP in the prediction of clinical progression in neuroinflammation, brain tumors, TBI, ischemic stroke, genetic disorders, neurodegeneration and other diseases in the CNS and to explore the potential therapeutic methods.

Mulberry (Morus alba L.) leaf water extract attenuates type 2 diabetes mellitus by regulating gut microbiota dysbiosis, lipopolysaccharide elevation and endocannabinoid system disorder.

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry (Morus alba L.) leaf is a well-known herbal medicine and has been used to treat diabetes in China for thousands of years. Our previous studies have proven mulberry leaf water extract (MLWE) could improve type 2 diabetes mellitus (T2D). However, it is still unclear whether MLWE could mitigate T2D by regulating gut microbiota dysbiosis and thereof improve intestinal permeability and metabolic dysfunction through modulation of lipopolysaccharide (LPS) and endocannabinoid system (eCBs). AIM OF STUDY: This study aims to explore the potential mechanism of MLWE on the regulation of metabolic function disorder of T2D mice from the aspects of gut microbiota, LPS and eCBs. MATERIALS AND METHODS: Gut microbiota was analyzed by high-throughput 16S rRNA gene sequencing. LPS, N-arachidonoylethanolamine (AEA) and 2-ararchidonylglycerol (2-AG) contents in blood were determined by kits or liquid phase chromatography coupled with triple quadrupole tandem mass spectrometry, respectively. The receptors, enzymes or tight junction protein related to eCBs or gut barrier were detected by RT-PCR or Western blot, respectively. RESULTS: MLWE reduced the serum levels of AEA, 2-AG and LPS, decreased the expressions of N-acylphophatidylethanolamine phospholipase D, diacylglycerol lipase-α and cyclooxygenase 2, and increased the expressions of fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA), alpha/beta hydrolases domain 6/12 in the liver and ileum and occludin, monoacylglycerol lipase and cannabinoid receptor 1 in the ileum of T2D mice. Furthermore, MLWE could change the abundances of the genera including Acetatifactor, Anaerovorax, Bilophila, Colidextribacter, Dubosiella, Gastranaerophilales, Lachnospiraceae_NK4A136_group, Oscillibacter and Rikenella related to LPS, AEA and/or 2-AG. Moreover, obvious improvement of MLWE treatment on serum AEA level, ileum occludin expression, and liver FAAH and NAAA expression could be observed in germ-free-mimic T2D mice. CONCLUSION: MLWE could ameliorate intestinal permeability, inflammation, and glucose and lipid metabolism imbalance of T2D by regulating gut microbiota, LPS and eCBs.

Study on the quality evaluation of the leaves of Croton tiglium from different regions based on quality markers.

METHODOLOGY: The chemical constituents of LCT were identified and quantified using high-performance liquid chromatography with a diode array detector. A characteristic fingerprint was then established and combined with multivariate statistical analysis of 16 common peaks and eight diterpenoids to identify the quality markers. INTRODUCTION: The leaves of Croton tiglium (LCT) have long been used in folk and ethnic medicine in China. Owing to the various regions, the chemical composition and content of LCT may differ, and hence, the quality of medicinal materials may be different. However, quality standards have not yet been established, although some studies have been conducted on their composition. OBJECTIVES: To quantitatively compare the chemical constituents of LCT from different areas and establish a quality evaluation of LCT based on quality markers. RESULTS: Eight quality markers selected based on 16 common peaks and three quality markers selected based on eight diterpenoids can distinguish LCT from three regions. The diterpenoids, including 12-O-acetylphorbol-13-(2-methylbutyrate) (3), 12-O-tiglyl-4-deoxy-4α-phorbol-13-acetate (6), and 12-O-(2-methyl)butyrylphorbol-13-tiglate (8), can be used as potential quality markers for the quality evaluation of LCT. CONCLUSION: Diterpenoids are highly efficient markers for quality evaluation. This study provides robust identification data and lays the foundation for formulating quality standards for LCT.

Diterpenoids with Schistosomula-Killing and Anti-Fibrosis Activities In Vitro from the Leaves of Croton tiglium.

The leaves of C. tiglium have been comprehensively researched for their structurally novel bioactive natural compounds, especially those with anti-schistosomiasis liver fibrosis activity, because ethyl acetate extract, which can be extracted from the leaves of C. tiglium, has good anti-schistosomiasis liver fibrosis effects. One new tigliane-type diterpene, 20-acetyl-13-O-(2-metyl)butyryl-phorbol (1), and nine known (2-10) analogues were isolated from the leaves of C. tiglium. Their structures were elucidated on the basis of spectroscopic analysis and ECD analysis. All diterpenoids had a stronger insecticidal effect on schistosomula, and compounds 2, 4, and 10 had good anti-liver-fibrosis effects. Furthermore, compared with the model group, compound 2 significantly downregulated the protein and mRNA expression of COL-I, COL-III, α-SMA, and TGF-ß1 on TGF-ß1-induced liver fibrosis in LX-2 cells. Meanwhile, compound 2 also regulated the expression of TGF-ß/Smad-pathway-related proteins. The results suggest that diterpenoids from C. tiglium may serve as potential schistosomula-killing and anti-liver-fibrosis agents in the future.

High-Performance Photodetectors Based on Semiconducting Graphene Nanoribbons.

The inherent zero-band gap nature of graphene and its fast photocarrier recombination rate result in poor optical gain and responsivity when graphene is used as the light absorption medium in photodetectors. Here, semiconducting graphene nanoribbons with a direct bandgap of 1.8 eV are synthesized and employed to construct a vertical heterojunction photodetector. At a bias voltage of -5 V, the photodetector exhibits a responsivity of 1052 A/W, outperforming previous graphene-based heterojunction photodetectors by several orders of magnitude. The achieved detectivity of 3.13 × 1013 Jones and response time of 310 µs are also among the best values for graphene-based heterojunction photodetectors reported until date. Furthermore, even under zero bias, the photodetector demonstrates a high responsivity and detectivity of 1.04 A/W and 2.45 × 1012 Jones, respectively. The work shows a great potential of graphene nanoribbon-based photodetection technology.

Sustainable Coating Based on Zwitterionic Functionalized Polyurushiol with Antifouling and Antibacterial Properties.

Zwitterionic polymer coatings facilitate the formation of hydration layers via electrostatic interactions on their surfaces and have demonstrated efficacy in preventing biofouling. They have emerged as a promising class of marine antifouling materials. However, designing multifunctional, environmentally friendly, and natural products-derived zwitterionic polymer coatings that simultaneously resist biofouling, inhibit protein adhesion, exhibit strong antibacterial properties, and reduce algal adhesion is a significant challenge. This study employed two diisocyanates as crosslinkers and natural urushiol and ethanolamine as raw materials. The coupling reaction of diisocyanates with hydroxyl groups was employed to synthesize urushiol-based precursors. Subsequently, sulfobetaine moieties were introduced into the urushiol-based precursors, developing two environmentally friendly and high-performance zwitterionic-functionalized polyurushiol antifouling coatings, denoted as HUDM-SB and IPUDM-SB. The sulfobetaine-functionalized polyurushiol coating exhibited significantly enhanced hydrophilicity, with the static water contact angle reduced to less than 60°, and demonstrated excellent resistance to protein adhesion. IPUDM-SB exhibited antibacterial efficacy up to 99.9% against common Gram-negative bacteria (E. coli and V. alginolyticus) and Gram-positive bacteria (S. aureus and Bacillus. sp.). HUDM-SB achieved antibacterial efficacy exceeding 95.0% against four bacterial species. Furthermore, the sulfobetaine moieties on the surfaces of the IPUDM-SB and HUDM-SB coatings effectively inhibited the growth and reproduction of algal cells by preventing microalgae adhesion. This zwitterionic-functionalized polyurushiol coating does not contain antifouling agents, making it a green, environmentally friendly, and high-performance biomaterial-based solution for marine antifouling.

Current non-invasive strategies for brain drug delivery: overcoming blood-brain barrier transport.

BACKGROUND: The blood-brain barrier (BBB) is a complex and dynamic structure that serves as a gatekeeper, restricting the migrations of most compounds and molecules from blood into the central nervous system (CNS). The BBB plays a crucial role in maintaining CNS physiological function and brain homeostasis. It can protect the CNS from the entrance of toxic and infectious agents, however, it also restricts the drug permeation into brain to play a therapeutic role. The BBB has been the biggest limiting hurdle to medications entering the brain excluding from the brain about 100% of large-molecule and more than 98% of all small-molecule neurotherapeutics. As a result, it is of inability for drug molecule to reach requisite concentrations within the brain. OBJECTIVE: With the aim of enhancing drug permeability and efficacy, a variety of strategies have been developed: invasive approaches, such as intraarterial delivery, intrathecal delivery, or administrating directly the drug intraventricularly and intracerebrally; non-invasive approaches that take advantage of innate BBB functions, using prodrugs, focused ultrasound, intranasal administration or nanotechnology. CONCLUSIONS: Here we mainly review recent developments and challenges related to non-invasive BBB-crossing techniques, whose benefits include higher efficacy, easier application, less treatment burden, better patient acceptability, and adherence. Additionally, we also analyze the potential of non-invasive methods in the treatment of CNS disorders and render them as a most suitable platform for the management of neurological diseases.

In vitro validation: GLY alleviates UV-induced corneal epithelial damage through the HMGB1-TLR/MyD88-NF-κB signaling pathway.

UV-induced corneal damage is a common ocular surface injury that usually leads to corneal lesions causing persistent inflammation. High mobility group box 1 (HMGB1) is identified as an inflammatory alarm in various tissue injuries. Here, this study first evaluates the repair effect of the HMGB1-selective inhibitor GLY in UV-induced corneal damage; Secondly, the inhibitory effect of GLY on UV-induced corneal damage induced inflammation and the potential therapeutic mechanism of GLY were studied. GLY effectively attenuates the expression of UV-induced inflammatory factors and HMGB1, TLR/MyD88, NF-κB signaling pathway genes at the mRNA and protein levels. In addition, RT-PCR and Western Blot experiments after knocking down HMGB1 and TLR2/9 genes showed that GLY alleviated corneal inflammation by inhibiting the HMGB1-TLR/MyD88 signaling pathway. The results of this study show that targeting HMGB1-NF-κB by GLY can alleviate the inflammatory response induced by UV induction.

Tannic Acid-Induced Gelation of Aqueous Suspensions of Cellulose Nanocrystals.

Nanocellulose hydrogels are a crucial category of soft biomaterials with versatile applications in tissue engineering, artificial extracellular matrices, and drug-delivery systems. In the present work, a simple and novel method, involving the self-assembly of cellulose nanocrystals (CNCs) induced by tannic acid (TA), was developed to construct a stable hydrogel (SH-CNC/TA) with oriented porous network structures. The gelation process is driven by the H-bonding interaction between the hydroxyl groups of CNCs and the catechol groups of TA, as substantiated by the atoms in molecules topology analysis and FTIR spectra. Interestingly, the assembled hydrogels exhibited a tunable hierarchical porous structure and mechanical moduli by varying the mass ratio of CNCs to TA. Furthermore, these hydrogels also demonstrate rapid self-healing ability due to the dynamic nature of the H-bond. Additionally, the structural stability of the SH-CNC/TA hydrogel could be further enhanced and adjusted by introducing coordination bonding between metal cations and TA. This H-bonding driven self-assembly method may promote the development of smart cellulose hydrogels with unique microstructures and properties for biomedical and other applications.

Numerical and experimental investigations on the jet and shock wave dynamics during the cavitation bubble collapsing near spherical particles based on OpenFOAM.

The interaction between cavitation bubbles and particles is essential for the operational performance many kinds of fluid machineries. In the present paper, jet dynamics and shock waves induced by the cavitation bubble collapsing near two spherical particles are numerically investigated based on OpenFOAM. The numerical scheme is validated by the experimental data obtained based on our high-speed camera cavitation system. Our results reveal that bubble split induced by annular jet is the primary feature during bubble collapsing with four typical cases defined. For the jet formation, the localized high pressure produced at the bubble split point is the main reason and the split point also serves as the source of the shock waves shown by the numerical schlieren. Furthermore, the nondimensional bubble-particle distance is the most paramount parameter influencing the jet phenomenon (e.g. jet velocity).

A central serotonin regulating gene polymorphism (TPH2) determines vulnerability to acute tryptophan depletion-induced anxiety and ventromedial prefrontal threat reactivity in healthy young men.

Serotonin (5-HT) has long been implicated in adaptive emotion regulation as well as the development and treatment of emotional dysregulations in mental disorders. Accumulating evidence suggests a genetic vulnerability may render some individuals at a greater risk for the detrimental effects of transient variations in 5-HT signaling. The present study aimed to investigate whether individual variations in the Tryptophan hydroxylase 2 (TPH2) genetics influence susceptibility for behavioral and neural threat reactivity dysregulations during transiently decreased 5-HT signaling. To this end, interactive effects between TPH2 (rs4570625) genotype and acute tryptophan depletion (ATD) on threat reactivity were examined in a within-subject placebo-controlled pharmacological fMRI trial (n = 51). A priori genotype stratification of extreme groups (GG vs. TT) allowed balanced sampling. While no main effects of ATD on neural reactivity to threat-related stimuli and mood state were observed in the entire sample, accounting for TPH2 genotype revealed an ATD-induced increase in subjective anxious arousal in the GG but not the TT carriers. The effects were mirrored on the neural level, such that ATD specifically reduced ventromedial prefrontal cortex reactivity towards threat-related stimuli in the GG carriers. Furthermore, the ATD-induced increase in subjective anxiety positively associated with the extent of ATD-induced changes in ventromedial prefrontal cortex activity in response to threat-related stimuli in GG carriers. Together the present findings suggest for the first time that individual variations in TPH2 genetics render individuals susceptible to the anxiogenic and neural effects of a transient decrease in 5-HT signaling.

Ultrastrong and Tough Urushiol-Based Ionic Conductive Double Network Hydrogels as Flexible Strain Sensors.

Ionic conductive hydrogels have attracted increasing research interest in flexible electronics. However, the limited resilience and poor fatigue resistance of current ionic hydrogels significantly restrict their practical application. Herein, an urushiol-based ionic conductive double network hydrogel (PU/PVA-Li) was developed by one-pot thermal initiation polymerization assisted with freeze-thaw cycling and subsequent LiCl soaking. Such a PU/PVA-Li hydrogel comprises a primary network of covalently crosslinked polyurushiol (PU) and a secondary network formed by physically crosslinked poly(vinyl alcohol) (PVA) through crystalline regions. The obtained PU/PVA-Li hydrogel demonstrates exceptional mechanical properties, including ultrahigh strength (up to 3.4 MPa), remarkable toughness (up to 1868.6 kJ/m3), and outstanding fatigue resistance, which can be attributed to the synergistic effect of the interpenetrating network structure and dynamic physical interactions between PU and PVA chains. Moreover, the incorporation of LiCl into the hydrogels induces polymer chain contraction via ionic coordination, further enhancing their mechanical strength and resilience, which also impart exceptional ionic conductivity (2.62 mS/m) to the hydrogels. Based on these excellent characteristics of PU/PVA-Li hydrogel, a high-performance flexible strain sensor is developed, which exhibits high sensitivity, excellent stability, and reliability. This PU/PVA-Li hydrogel sensor can be effectively utilized as a wearable electronic device for monitoring various human joint movements. This PU/PVA-Li hydrogel sensor could also demonstrate its great potential in information encryption and decryption through Morse code. This work provides a facile strategy for designing versatile, ultrastrong, and tough ionic conductive hydrogels using sustainable natural extracts and biocompatible polymers. The developed hydrogels hold great potential as promising candidate materials for future flexible intelligent electronics.

Nine new species of black lichenicolous fungi from the genus Cladophialophora (Chaetothyriales) from two different climatic zones of China.

Lichenicolous fungi are parasites of lichens. Many of these fungi are referred to as "black fungi". A diversity of these black fungi include species that are pathogenic to humans and plants. A majority of black fungi reside in the phylum Ascomycota within the sub-classes Chaetothyriomycetidae and Dothideomycetidae. To explore the diversity of lichenicolous "black fungi" associated with lichens in China, we conducted several field surveys in the Inner Mongolia Autonomous Region and Yunnan Province between 2019 and 2020. We recovered 1,587 fungal isolates from the lichens collected during these surveys. During the preliminary identification of these isolates using the complete internal transcribed spacer (ITS), partial large subunit of nuclear ribosomal RNA gene (LSU), and small subunit of nuclear ribosomal RNA gene (SSU), we identified 15 fungal isolates from the genus Cladophialophora. However, these isolates had low sequence similarities with all known species from the genus. Therefore, we amplified additional gene regions, such as, translation elongation factor (TEF) and partial ß-tubulin gene (TUB), and constructed a multi-gene phylogeny using maximum likelihood, maximum parsimony, and Bayesian inference. In our datasets, we included type sequences where available for all Cladophialophora species. Phylogenetic analyses revealed that none of the 15 isolates belonged to any of the previously described species in the genus. Therefore, using both morphological and molecular data, we classified these 15 isolates as nine new species within the genus Cladophialophora: C. flavoparmeliae, C. guttulate, C. heterodermiae, C. holosericea, C. lichenis, C. moniliformis, C. mongoliae, C. olivacea, and C. yunnanensis. The outcome from this study shows that lichens are an important refugia for black lichenicolous fungi, such as those from Chaetothyriales.

Dapagliflozin attenuates myocardial hypertrophy via activating the SIRT1/HIF-1α signaling pathway.

As a sodium-glucose transporter 2 inhibitor (SGLT2i), the cardioprotective benefits of Dapagliflozin (DAPA) are now widely appreciated. However, the underlying mechanism of DAPA on angiotensin II (Ang II)-induced myocardial hypertrophy has never been evaluated. In this study, we not only investigated the effects of DAPA on Ang II-induced myocardial hypertrophy, but explored its underlying mechanisms. Mice were injected with Ang II (500 ng /kg/min) or saline solution as control, followed by intragastric administration DAPA (1.5 mg/kg/day) or saline for four weeks. DAPA treatment alleviated the condition of decrease in left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) caused by Ang II. In addition, DAPA treatment significantly alleviated Ang II-induced elevation of the ratio of heart weight to tibia length, as well as cardiac injury and hypertrophy. In mice stimulated with Ang II, the degree of myocardial fibrosis and upregulation of the markers of cardiac hypertrophy (atrial natriuretic peptide, ANP and B-type natriuretic peptide, BNP) were attenuated by DAPA. What's more, DAPA partially reversed the Ang II-induced upregulation of HIF-1α and the decrease in levels of SIRT1. Taken together, activating the SIRT1/HIF-1α signaling pathway was found to confer a protective effect against experimental myocardial hypertrophy in mice induced by Ang II, demonstrating its potential as an effective therapeutic target for pathological cardiac hypertrophy.