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Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvβ3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE’s influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvβ3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvβ3. Activation of the integrin αvβ3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

In this paper, the catalytic pyrolysis of Jimsar oil shale was studied using CoCl2·6H2O as a catalyst. The thermogravimetric analysis (TGA) was carried out on oil shale samples with the catalyst added. The kinetic analysis of the pyrolysis reaction of each sample was performed using the main curve method and several model-free methods. The results showed that CoCl2·6H2O could not only reduce the average activation energy of oil shale pyrolysis from 216 kJ/mol to 163 kJ/mol, but also decrease the pyrolysis temperature by about 100 °C.

Summary: Short open reading frame-encoded peptides (SEPs) are generally 2–100 amino acids in length and participate in various biological processes of the organism. The brain is the central hub of life activities, where different regions perform distinct functions. To characterize SEPs in brain regions, we analyzed SEPs in five mouse brain areas, including hippocampus, frontal cortex, temporal cortex, occipital cortex, and parietal cortex, with mass spectrometry-based proteomics. We obtained 1,095 proteins with less than 100 amino acids and identified 373 SEPs. Approximately 83% of these SEPs are reported for the first time. Half of them are encoded by ncRNA, and nearly one-third can find orthology across species. Specific SEPs were identified in each brain region. For example, IP_1018875 was identified in the frontal cortex, possibly related to autophagy and neuronal signaling. These results enrich the proteome of the mouse brain and help facilitate subsequent studies on the function of SEPs.

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) has been associated with vascular tone and blood pressure (BP), however, its role in the genesis of hypertension remains elusive. In the present study, we investigated the regulating effect of CFTR on angiotensin II (Ang II) -induced hypertension and defined the molecular role of CFTR in vasoconstriction. Results: We found that CFTR mRNA and protein expression were markedly down-regulated in the arteries from Ang II induced hypertensive animals. During the development of hypertension, BP of Cftr-⁣/- mice was significantly higher than that of Cftr+⁣/+ mice. Arteries from Cftr-⁣/- mice or pre-incubated with CFTR specific inhibitor CFTR(inh)-172 exhibited a greater contractile response to Ang II. In vascular smooth muscle cells (VSMCs), the phosphorylation of myosin light chain (MLC), which is the core of VSMCs contraction, was negatively modulated by CFTR. Furthermore, intracellular Ca2+ concentration ([Ca2+]i) rise in response to Ang II was negatively modulated by CFTR, while no alteration was observed in resting VSMCs. Ras homolog family member A/Rho-associated protein kinase (RhoA/Rock) mediated phosphorylation of myosin phosphatase target subunit 1 (MYPT1), a regulator of MLC phosphorylation, was negatively modulated by CFTR in both resting and Ang II-stimulated VSMCs. Conclusions: This study demonstrates that CFTR is a negative regulator of vasoconstriction and hypertension, and the underlying mechanism contains two possible pathways: (1) in resting VSMCs, CFTR altered MLC phosphorylation through RhoA/Rock pathway; (2) in Ang II stimulated VSMCs, the regulating effect was mediated by both Ca2+ influx and RhoA/Rock mediated pathway.

Hydrogen sulfide (H2S) plays prominent multifunctional roles in the mediation of various physiological processes and stress responses to plants. In this study, hydroponic experiments were carried out to explore the effects of NaHS pretreatment on the growth of wheat (Triticum aestivum L.) under 50 μM cadmium (Cd). Compared with Cd treatment alone, 50 μM NaHS pretreatment increased the plant height, soluble sugar content of shoots and roots, and dry weight of shoots and roots under Cd stress, while the Cd concentration of shoots and roots was significantly reduced by 18.1% and 25.9%, respectively. Meanwhile, NaHS pretreatment protected the photosynthetic apparatus by increasing the net photosynthetic rate and PSII electron transportation rate of wheat leaves under Cd stress. NaHS pretreatment significantly increased the soluble sugar content to maintain the osmotic pressure balance of the leaf cells. The gene expression results associated with photosynthetic carbon assimilation and sucrose synthesis in wheat leaves suggested that the NaHS pretreatment significantly up-regulated the expression of TaRBCL, TaRBCS, and TaPRK, while it down-regulated the expression of TaFBA, TaSuSy, TaSAInv, and TaA/NInv. In summary, NaHS pretreatment improved the resistance of wheat seedlings under Cd stress by increasing the rate of photosynthesis and regulating the expression of genes related to sugar metabolism.

Cadmium (Cd)-contaminated soil has been receiving increasing attention worldwide due to the great harm it causes via food-chain enrichment through crops such as wheat. However, there is little research regarding the effects of mannose (MAN) on plants in response to Cd stress. Hence, hydroponic and potted soil experiments were conducted to investigate the mitigation effects of MAN on wheat under Cd stress and the possible mechanism. Compared with Cd treatment alone, foliar spraying of 160 μM MAN significantly reduced the Cd accumulation in shoots and increased the Cd retention in roots. The content of hemicellulose was increased by MAN treatment, and the proportion of Cd retained by hemicellulose in the cell wall of roots was increased. Furthermore, 160 μM MAN significantly reduced the water-extracted and ethanol-extracted Cd in roots, which are easily transported to shoots. In potted soil experiments using Cd-contaminated soil, MAN reduced the Cd content in wheat grain by 26.3%, compared with the control. These findings indicate that foliar spraying of 160 μM MAN resulted in less Cd being transported from roots to shoots by increasing the Cd retention in the cell wall and changing the Cd chemical forms in roots, which promoted wheat growth and reduced the Cd concentration in wheat grain.

Small open reading frame encoded peptides (SEPs), also called microproteins, play a vital role in biological processes. Plenty of their open reading frames are located within the non-coding RNA (ncRNA) range. Recent research has demonstrated that ncRNA-encoded polypeptides have essential functions and exist ubiquitously in various tissues. To better understand the role of microproteins, especially ncRNA-encoded proteins, expressed in different tissues, we profiled the proteomic characterization of five mouse tissues by mass spectrometry, including bottom-up, top-down, and de novo sequencing strategies. Bottom-up and top-down with database-dependent searches identified 811 microproteins in the OpenProt database. De novo sequencing identified 290 microproteins, including 12 ncRNA-encoded microproteins that were not found in current databases. In this study, we discovered 1,074 microproteins in total, including 270 ncRNA-encoded microproteins. From the annotation of these microproteins, we found that the brain contains the largest number of neuropeptides, while the spleen contains the most immunoassociated microproteins. This suggests that microproteins in different tissues have tissue-specific functions. These unannotated ncRNA-coded microproteins have predicted domains, such as the macrophage migration inhibitory factor domain and the Prefoldin domain. These results expand the mouse proteome and provide insight into the molecular biology of mouse tissues.

Isaridin E, a cyclodepsipeptide isolated from the marine-derived fungus Amphichorda felina (syn. Beauveria felina) SYSU-MS7908, has been demonstrated to possess anti-inflammatory and insecticidal activities. Here, we first found that isaridin E concentration-dependently inhibited ADP-induced platelet aggregation, activation, and secretion in vitro, but did not affect collagen- or thrombin-induced platelet aggregation. Furthermore, isaridin E dose-dependently reduced thrombosis formation in an FeCl3-induced mouse carotid model without increasing the bleeding time. Mechanistically, isaridin E significantly decreased the ADP-mediated phosphorylation of PI3K and Akt. In conclusion, these results suggest that isaridin E exerts potent antithrombotic effects in vivo without increasing the risk of bleeding, which may be due to its important role in inhibiting ADP-induced platelet activation, secretion and aggregation via the PI3K/Akt pathways.

Soil pollution by heavy metals (HMs) is a major environmental problem around the world. The addition of biowaste-based stabilizers for HM remediation has recently gained attention due to its relatively low cost and eco-risk, abundance, ease of operation, and quick remediation results. Among these stabilizers, shell (crustacean shell, bivalve shell, and eggshell), starfish, and bone-based stabilizers are particularly attractive because of their high Ca and P contents, allowing for highly efficient HM immobilization and simultaneous supplement of nutrients to the soil. However, a comprehensive review focusing on these stabilizers is currently missing. Therefore, this review attempts to summarize the HM immobilization efficiency of these stabilizers and the mechanisms associated with HM stabilization, and perform an operation cost estimation and cost comparison. Cost comparisons among different stabilizers are widely ignored in reviews due to the lack of reliable cost estimation tools or methods. However, for practical application in soil remediation, cost is one of the most important factors to consider. Thus, a simple but reasonable cost estimation method is developed and discussed in this review. Bivalve shell-based stabilizers demonstrated the most promising results for the immobilization of soil HMs in terms of higher performance and lower cost. Current research limitations, challenges, and recommendations regarding possible future research directions are also provided. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to understand the relationship between the multiple chronic conditions (MCC), mental health and cognitive function of older adults in the community, and to propose a hypothesis that depressive symptom mediate the number of chronic diseases and cognitive impairment in older adults. Method: Participants aged 65 years and older from 35 communities in 14 cities in Guangxi, China were recruited. The residents' depressive symptom (PHQ-9) and cognitive status (AD-8) were evaluated, Chi-square test was used to explore the effects of different socio-demographic characteristics on depressive symptom and cognitive impairment. Pearson correlation analysis and the process model 4 were used to explore the relationship between the number of chronic diseases, depressive symptom and cognitive impairment. Result: A total of 11,582 older adults were included in our analysis. The rate of MCC reaching 26.53%. Hypertension combined with diabetes accounts for the highest proportion of two chronic diseases (13.2%). Among the combination of three chronic diseases, the highest incidence of coexisting hypertension combined with cervical/lumbar spondylosis, and rheumatoid arthritis (7.1%). In this study, depression symptoms accounted for 12.9% of older adults aged 65 and above, and cognitive impairment accounted for 27.4%. Female, older age, reside in urban areas, lower educational levels, no spouse, live alone, and MCC were risk factors for depressive symptom and cognitive impairment in older adults (P<0.05). Depressive symptom had a mediating effect in the number of chronic diseases and cognitive impairment, and the mediating effect (1.109) accounted for 44.13% of the total effect (0.247). Conclusion: The mental health of the older adult needs to be taken seriously, and improving depressive symptom can reduce the occurrence of cognitive impairment in older patients with MCC to a certain extent. [ABSTRACT FROM AUTHOR]

Background: Adipose stem cell‐derived exosomes (ADSC‐EXO) and botulinum toxin type A (BTX‐A) individually showed a therapeutic effect on skin wound repair. Aims: This study investigated their synergistic effect on promoting skin wound healing in vitro and in vivo and the underlying molecular events. Methods: ADSCs were isolated from Sprague–Dawley (SD) rats to obtain ADSC‐EXO by ultrafiltration and ultracentrifugation and were confirmed using nanoparticle tracking analysis and transmission electron microscopy. Human skin fibroblasts (HSF) were cultured and treated with or without ADSC‐EXO, BTX‐A, or their combination. Changes in cell phenotypes and protein expression were analyzed using different in vitro assays, and a rat skin wound model was used to assess their in vivo effects. Results: The isolated ADSC‐EXO from primarily cultured ADSCs had a circular vesicle shape with a 30–180 nm diameter. Treatment of HSF with ADSC‐EXO and/or BTX‐A significantly accelerated HSF migration in vitro and skin wound healing in a rat model. Moreover, ADSC‐EXO plus BTX‐A treatment dramatically induced VEGFA expression but reduced COL III and COL I levels in vivo. ADSC‐EXO and/or BTX‐A treatment significantly upregulated TGF‐β3 expression on Day 16 after surgery but downregulated TGF‐β1 expression, suggesting that ADSC‐EXO plus BTX‐A promoted skin wound healing and reduced inflammatory cell infiltration. Conclusions: The ADSC‐EXO plus BTX‐A treatment demonstrated a synergistic effect on skin wound healing through upregulation of VEGF expression and the TGF‐β3/TGF‐β1 and COL III/COL I ratio. [ABSTRACT FROM AUTHOR]