Silencing BMAL1 promotes M1/M2 polarization through the LDHA/lactate axis to promote GBM sensitivity to bevacizumab.

OBJECTIVE: Glioblastoma (GBM) has poor clinical prognosis due to limited treatment options. In addition, the current treatment regimens for GBM may only slightly prolong patient survival. The aim of this study was to assess the role of BMAL1 in the immune microenvironment and drug resistance of GBM. METHODS: GBM cell lines with stable BMAL1 knockdown or LDHA overexpression were constructed, and functionally characterized by the CCK8, EdU incorporation, and transwell assays. In vivo GBM model was established in C57BL/6J mice. Flow cytometry, ELISA, immunofluorescence, and RT-qPCR were performed to detect macrophage polarization. Lactate production, pathological changes, and the expression of glycolytic proteins were analyzed by HE staining, immunohistochemistry, biochemical assays, and Western blotting. RESULTS: BMAL1 silencing inhibited the malignant characteristics, lactate production, and expression of glycolytic proteins in GBM cells, and these changes were abrogated by overexpression of LDHA or exogenous lactate supplementation. Furthermore, BMAL1 knockdown induced M1 polarization of macrophages, and inhibited M2 polarization and angiogenesis in GBM cells in conditioned media. Overexpression of LDHA or presence of exogenous lactate inhibited BMAL1-induced M1 polarization and angiogenesis. Finally, BMAL1 silencing and bevacizumab synergistically inhibited glycolysis, angiogenesis and M2 polarization, and promoted M1 polarization in vivo, thereby suppressing GBM growth. CONCLUSION: BMAL1 silencing can sensitize GBM cells to bevacizumab by promoting M1/M2 polarization through the LDHA/lactate axis.

Hollow Zeolite Nanoreactor with Double Shells for Methanol Aromatization: Explicit Recognition on Catalytic Function of Inverse Elemental Zone and Shell-Cavity.

Core@shell catalyst composited of dual aluminosilicate zeolite can effectively regulate the distribution of acid sites to control hydrocarbon conversion process for the stable formation of target product. However, the diffusion restriction reduces the accessibility of inner active sites and affects synergy between core and shell. Herein, hollow ZSM-5 zeolite nanoreactor with inverse aluminum distribution and double shells are prepared and employed for methanol aromatization. It is demonstrated that the intershell cavity alleviated the steric hindrance from zeolites channel and provided more paths and pore entrance for guest molecule. Correspondingly, olefin intermediates generated from methanol over the external shell are easier to adsorb at internal acid sites for further reactions. Importantly, the diffusion of generated aromatic macromolecules to the external surface is also promoted, which slows down the formation of internal coke, and ensures the use of internal acid sites for aromatization. The aromatics selectivity of the nanoreactor remained at 8% after 154 h, while that of solid core@shell catalyst decreased to 2% after 75 h. This finding promises broader insight to improve internal active site utilization of core@shell catalyst at the diffusion level and can be great aid in the flexible design of multifunctional nanoreactors to enhance the relay efficiency.

Speciation analysis and toxicity evaluation of arsenolipids-an overview focusing on sea food.

Arsenic, which can be divided into inorganic and organic arsenic, is a toxic metalloid that has been identified as a human carcinogen. A common source of arsenic exposure in seafood is arsenolipid, which is a complex structure of lipid-soluble organic arsenic compounds. At present, the known arsenolipid species mainly include arsenic-containing fatty acids (AsFAs), arsenic-containing hydrocarbons (AsHCs), arsenic glycophospholipids (AsPLs), and cationic trimethyl fatty alcohols (TMAsFOHs). Furthermore, the toxicity between different species is unique. However, the mechanism underlying arsenolipid toxicity and anabolism remain unclear, as arsenolipids exhibit a complex structure, are present at low quantities, and are difficult to extract and detect. Therefore, the objective of this overview is to summarize the latest research progress on methods to evaluate the toxicity and analyze the main speciation of arsenolipids in seafood. In addition, novel insights are provided to further elucidate the speciation, toxicity, and anabolism of arsenolipids and assess the risks on human health.

Total Glucosides of Paeony Ameliorate Myocardial Injury in Chronic Heart Failure Rats by Suppressing PARP-1.

Total glucosides of paeony (TGP) have a potential protective effect on chronic heart failure (CHF) rats, but the mechanism remains unclear. PARP inhibition prevents the decrease in myocardial contractility. Therefore, we aim to investigate the effects and mechanisms of TGP on CHF and the role of PARP-1 in CHF. Left anterior descending ligation rats and adriamycin-treated H9C9 cells were used as CHF models, and captopril as a positive control for in vivo experiments. We found that TGP alleviated myocardial remodeling and improved cardiac morphology and function. TGP also reduced myocardial apoptosis and autophagy, decreased inflammatory factor release, and inhibited the PARP-1 and NF-κB proteins. Through cell transfection, we found that PAPR-1 knockdown inhibited NF-κB nuclear translocation. Additionally, TGP inhibited apoptosis, autophagy, and inflammation in CHF cells, while PARP-1 overexpression partially antagonized them. In conclusion, TGP has the potential to improve CHF and PARP-1 may be a potential target.

Exercise improves cardiac function and attenuates myocardial inflammation and apoptosis by regulating APJ/STAT3 in mice with stroke.

Stroke can induce cardiac dysfunction without a primary cardiac disease. Exercise can promote the overall rehabilitation of stroke patients and be beneficial for all kinds of heart diseases. However, the mechanisms underlying the protective effects of exercise in stroke-induced cardiac dysfunction are poorly understood. Hence, we aimed to distinguish the different effects of acute and long-term exercise and further study the mechanism of protection against cardiomyopathy caused by stroke. Mice underwent a single acute session or long-term exercise for 30 days, followed by middle cerebral artery occlusion surgery. The expression of apoptosis-related proteins and proinflammatory factors in the heart was evaluated. Then, overexpression of apelin peptide jejunum (APJ) transfected adeno-associated virus type 9 (AAV9) and inhibition of signal transducer and activator of transcription 3 (STAT3) by Stattic were used in stroke mice or hypoxic cardiomyocytes. ML221 were used to inhibit APJ activity in exercise mouse. Thereafter, changes in apoptotic and proinflammatory factors were evaluated. The results demonstrated that chronic exercise prevented myocardial inflammation, apoptosis and cardiac dysfunction after stroke. However, acute exercise did not have similar effects. Exercise maintained the levels of APJ expression and decreased phosphorylated-STAT3 (p-STAT3) activation to protect cardiomyocytes. Moreover, APJ overexpression promoted cardiomyocyte survival and reduced p-STAT3 levels. STAT3 inhibition also reduced apoptosis and proinflammatory factors in mice hearts. Conversely, the protective effect of exercise was eliminated by APJ inhibition. This study showed that exercise can maintain APJ expression and inhibit p-STAT3, thus, conferring protection against myocardial inflammation and apoptosis induced by stroke.

Induction of Hibernation and Changes in Physiological and Metabolic Indices in Pelodiscus sinensis.

Pelodiscus sinensis (P. sinensis) is a commonly cultivated turtle species with a habit of hibernation. To study the changes in histone expression and methylation of P. sinensis during hibernation induction, a model was established by artificial induction. Physiological and metabolic indices were measured, and the expression and localization of histone (H1, H2A, H2B, H3, and H4) and methylation-related genes (ASH2L, KMT2A, KMT2E, KDM1A, KDM1B, and KDM5A) were measured by quantitative PCR, immunohistochemistry, and Western blot analysis. The results indicated that the metabolism, antioxidation index, and relative expression of histone methyltransferase were significantly decreased (p < 0.05), whereas the activity and expression of histone demethyltransferase were significantly increased (p < 0.05). Although our results showed significant changes in physiological and gene expression after hibernation induction, we could not confirm that P. sinensis entered deep hibernation. Therefore, for the state after cooling-induced hibernation, cold torpor might be a more accurate description. The results indicate that the P. sinensis can enter cold torpor through artificial induction, and the expression of histones may promote gene transcription. Unlike histones expressed under normal conditions, histone methylation may activate gene transcription during hibernation induction. Western blot analysis revealed that the ASH2L and KDM5A proteins were differentially expressed in the testis at different months (p < 0.05), which may perform a role in regulating gene transcription. The immunohistochemical localization of ASH2L and KDM5A in spermatogonia and spermatozoa suggests that ASH2L and KDM5A may perform a role in mitosis and meiosis. In conclusion, this study is the first to report changes in histone-related genes in reptiles, which provides insight for further studies on the physiological metabolism and histone methylation regulation of P. sinensis during the hibernation induction and hibernation period.

Importance of comprehensive genetic testing for patients with suspected vascular Ehlers-Danlos syndrome: a family case report and literature review.

Vascular Ehlers-Danlos syndrome (vEDS), the most severe type of Ehlers-Danlos syndrome, is caused by an autosomal-dominant defect in the COL3A1 gene. In this report, we describe the clinical history, specific phenotype, and genetic diagnosis of a man who died of vEDS. The precise diagnosis of this case using whole-exome sequencing provided solid evidence for the cause of death, demonstrating the practical value of genetic counseling and analysis. Early diagnosis for the proband's son, who was also affected by vEDS, revealed initial complications of vEDS in early childhood, which have rarely been reported. We also reviewed the literature on COL3A1 missense mutations and related phenotypes. We identified an association between digestion tract events and non-glycine missense variants, which disproves a previous hypothesis regarding the genotype-phenotype correlation of vEDS. Our results demonstrate the necessity of offering comprehensive genetic testing for every patient suspected of having vEDS.

Protection and Damage Repair Mechanisms Contributed To the Survival of Chroococcidiopsis sp. Exposed To a Mars-Like Near Space Environment.

Chroococcidiopsis spp. can withstand extremely harsh environments, including a Mars-like environment. However, studies are lacking on the molecular mechanisms of Chroococcidiopsis sp. surviving in Mars-like environments. In the HH-21-5 mission, the desert cyanobacterium Chroococcidiopsis sp. was exposed to a Mars-like environment (near space; 35 km altitude) for 4 h, and a single-factor environment of near space was simulated on the ground. We investigated the survival and endurance mechanisms of Chroococcidiopsis sp. ASB-02 after exposing it to near space by studying its physiological and transcriptional properties. After the exposure, Chroococcidiopsis sp. ASB-02 exhibited high cell viability, although photosystem II activity decreased and the levels of reactive oxygen species increased. The single-factor simulation experiments revealed that for the survival of Chroococcidiopsis sp. ASB-02 in near space, UV radiation was the most important limiting factor, and it was followed by temperature. The near space environment triggered multiple metabolic pathway responses in Chroococcidiopsis sp. ASB-02. The upregulation of extracellular polysaccharides as well as carotenoid and scytonemin biosynthesis genes in response to UV radiation attenuated the extent of radiation reaching the cells. At the same time, genes related to protein synthesis were upregulated in response to the low temperature, overcoming the decrease in metabolic activity that was caused by the low temperature. In near space and after rehydration, the genes involved in various DNA and photosystem II repair pathways were upregulated. This reflected the damage to the DNA and photosystem II protein subunits in cells during the flight and suggested that repair mechanisms play an important role in the recovery of Chroococcidiopsis sp. ASB-02. IMPORTANCE This study reported that the protective and repair mechanisms of Chroococcidiopsis sp. ASB-02 contributed to its endurance ability in a Mars-like near space environment. In Chroococcidiopsis sp. ASB-02, a Mars-like near space environment activated the expression of genes involved in extracellular polysaccharides (EPS), carotenoid, scytonemin, and protein syntheses, which provided additional protection. Additionally, the cell damage repair process enhanced the recovery rate of Chroococcidiopsis sp. ASB-02 after the flight. This study will help to enhance the understanding of the tolerance mechanism of Chroococcidiopsis sp. and to provide important guidance as to the survival requirements for microbial life in a Mars-like environment.

M378 exhibits anti-inflammatory activities through NLRP3 signaling pathway.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used drugs due to their values in attenuating pain, fever and inflammation. Unfortunately, conspicuous adverse effects, such as gastrointestinal (GI) damage and/or cardiovascular events have impeded their application in clinic. M378 is a novel hydrogen sulfide-releasing NSAIDs with uncompromised potency and negligible toxicity compared to the existing NSAIDs. However, its anti-inflammatory activity and mechanism are still an enigma. Here we investigated the effect of M378 on the NLRP3 inflammasome signaling pathway and addressed the underlying molecular mechanism. Our data in vitro showed that M378 dose-dependently inhibited the cleavage of Caspase-1 and the secretion of active IL-1ß and blocked NLRP3-dependent pyroptosis in LPS-primed J774A.1 macrophages. Furthermore, M378 remarkably inhibited upstream ASC oligomerization and ROS production regarding the process of NLRP3 inflammasome assembly. Our data in vivo demonstrated that M378 protected mice from acute liver injury, reducing the levels of ALT/AST and IL-1ß and improving hepatic pathological damages. Immunoblot analysis revealed that M378 inhibited the expressions of Caspase-1 and IL-1ß in liver tissues of ALI mice. We also showed that M378 alleviated IL-1ß secretion and peritoneal neutrophils infiltration in MSU-elicited acute peritonitis mice. In conclusion, M378 exerted its anti-inflammatory effect both in vitro and in vivo and its mechanisms are at least connected to its inhibitory performance on the generation of ASC oligomers and ROS production. These findings give an insight. into the molecular mechanism of hydrogen sulfide-releasing NSAIDs and support a potent therapeutic role of M378 in the treatment of NLRP3-driven inflammatory diseases.

Friend or foe: RIG- I like receptors and diseases.

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), which are pivotal sensors of RNA virus invasions, mediate the transcriptional induction of genes encoding type I interferons (IFNs) and proinflammatory cytokines, successfully establishing host antiviral immune response. A few excellent reviews have elaborated on the structural biology of RLRs and the antiviral mechanisms of RLR activation. In this review, we give a basic understanding of RLR biology and summarize recent findings of how RLR signaling cascade is strictly controlled by host regulatory mechanisms, which include RLR-interacting proteins, post-translational modifications and microRNAs (miRNAs). Furthermore, we pay particular attention to the relationship between RLRs and diseases, especially how RLRs participate in SARS-CoV-2, malaria or bacterial infections, how single-nucleotide polymorphisms (SNPs) or mutations in RLRs and antibodies against RLRs lead to autoinflammatory diseases and autoimmune diseases, and how RLRs are involved in anti-tumor immunity. These findings will provide insights and guidance for antiviral and immunomodulatory therapies targeting RLRs.

Cell damage repair mechanism in a desert green algae Chlorella sp. against UV-B radiation.

The protective ozone layer is continually depleting owing to an increase in the levels of solar UV-B radiation, which has harmful effects on organisms. Algae in desert soil can resist UV-B radiation, but most research on the radiation resistance of desert algae has focused on cyanobacteria. In this study, we found that desert green algae, Chlorella sp., could maintain high photosynthetic activity under UV-B stress. To examine the tolerance mechanism of the desert green algae photosystem, we observed the physiological and transcriptome-level responses of Chlorella sp. to high doses of UV-B radiation. The results showed that the reactive oxygen species (ROS) content first increased and then decreased, while the malondialdehyde (MDA) content revealed no notable lipid peroxidation during the UV-B exposure period. These results suggested that Chlorella sp. may have strong system characteristics for scavenging ROS. The antioxidant enzyme system showed efficient alternate coordination, which exhibited a protective effect against enhanced UV-B radiation. DNA damage and the chlorophyll and soluble protein contents had no significant changes in the early irradiation stage; UV-B radiation did not induce extracellular polysaccharides (EPS) synthesis. Transcriptomic data revealed that a strong photosynthetic system, efficient DNA repair, and changes in the expression of genes encoding ribosomal protein (which aid in protein synthesis and improve resistance) are responsible for the high UV-B tolerance characteristics of Chlorella sp. In contrast, EPS synthesis was not the main pathway for UV-B resistance. Our results revealed the potential cell damage repair mechanisms within Chlorella sp. that were associated with high intensity UV-B stress, thereby providing insights into the underlying regulatory adaptations of desert green algae.

BMAL1 may be involved in angiogenesis and peritumoral cerebral edema of human glioma by regulating VEGF and ANG2.

The rhythm gene BMAL1 (Brain and Muscle ARNT-Like 1) may play an important role in glioma tolerance for anti-angiogenesis therapy. In humans with glioma of different pathological grades, BMAL1 expression was significantly different, and the expression of ANG2 (Angiopoietin 2) and VEGF (Vascular endothelial growth factor) was positively correlated with the expression of BMAL1. Additionally, BMAL1 expression is positively correlated with the microvascular density and peritumoral edema of glioma. According to in vitro experiments, silencing the expression of BMAL1 in primary glioma cells results in a decrease in the expression of VEGF. In contrast, overexpression of BMAL1 promotes the expression of ANG2 and VEGF via HIF-1a pathway. Therefore, BMAL1 likely participates in the angiogenesis of glioma by modulating ANG2 and VEGF expression, alters the therapeutic effect of anti-angiogenic treatments, and promotes peritumoral brain edema of glioma.

Natural Language Processing Algorithms for Normalizing Expressions of Synonymous Symptoms in Traditional Chinese Medicine.

BACKGROUND: The modernization of traditional Chinese medicine (TCM) demands systematic data mining using medical records. However, this process is hindered by the fact that many TCM symptoms have the same meaning but different literal expressions (i.e., TCM synonymous symptoms). This problem can be solved by using natural language processing algorithms to construct a high-quality TCM symptom normalization model for normalizing TCM synonymous symptoms to unified literal expressions. METHODS: Four types of TCM symptom normalization models, based on natural language processing, were constructed to find a high-quality one: (1) a text sequence generation model based on a bidirectional long short-term memory (Bi-LSTM) neural network with an encoder-decoder structure; (2) a text classification model based on a Bi-LSTM neural network and sigmoid function; (3) a text sequence generation model based on bidirectional encoder representation from transformers (BERT) with sequence-to-sequence training method of unified language model (BERT-UniLM); (4) a text classification model based on BERT and sigmoid function (BERT-Classification). The performance of the models was compared using four metrics: accuracy, recall, precision, and F1-score. RESULTS: The BERT-Classification model outperformed the models based on Bi-LSTM and BERT-UniLM with respect to the four metrics. CONCLUSIONS: The BERT-Classification model has superior performance in normalizing expressions of TCM synonymous symptoms.

Exposure of cyanobacterium Nostoc sp. to the Mars-like stratosphere environment.

During the HH-19-2 flight mission of the Chinese Scientific Experimental System, dried Nostoc sp. cells were exposed to the stratosphere environment (32,508 m altitude) for 3 h and 22 min. The atmospheric pressure, temperature, relative humidity, and ionizing and non-ionizing radiation levels at that altitude are similar to those on the surface of Mars. Although analyses revealed decreased photosynthetic activity, a decline in autofluorescence, and damage to the cellular morphology in the flight-exposed sample, the death rate was low (28%). Physiological changes were not obvious after the exposure to the Mars-like vacuum conditions. The ground-exposed samples showed a similar trend to the flight-exposed samples, but the damage was relatively slight. RNA-sequencing data revealed a number of affected metabolic pathways: photosynthetic system and CO2 fixation function, activation of antioxidant systems, heat shock protein, DNA repair, and protein synthesis. Results suggest that Nostoc sp. has the potential to survive in a Mars-like environment and that it may be a suitable pioneer species to colonize Mars in the future in closed life-support systems (base) or in localities with relatively suitable conditions for life, such as localities with water available.

BATF2 balances the T cell-mediated immune response of CADM with an anti-MDA5 autoantibody.

OBJECTIVES: Clinically amyopathic dermatomyositis (CADM) is a subtype of dermatomyositis (DM) characterized by low-grade or absent muscle inflammation but frequent and rapidly progressive interstitial lung disease (RP-ILD) and skin ulcers with anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibodies. Basic leucine zipper transcription factor ATF-like 2 (BATF2) is thought to function as an inhibitor of tumours and inflammation. Here, we aimed to investigate the roles of BATF2 in Th cell differentiation of CADM with an anti-MDA5 autoantibody (anti-MDA5+ CADM). METHODS: Naive CD4+ T cells from human peripheral blood mononuclear cells (PBMCs) of healthy controls (HCs) were isolated and then cultured with IL-12, TGF-ß or TGF-ß plus IL-6 following anti-CD3 and anti-CD28 stimulations. The expression of BATF2 was measured by real-time PCR. The percentages of Th1, Th17 and Treg CD4+ T cells were detected by flow cytometry. BATF2 knockdown of CD4+ T cells was performed using small interfering RNAs (siRNAs). RESULTS: The expression of BATF2 in PBMCs was higher in anti-MDA5+ CADM patients than in healthy controls. The BATF2 mRNA expression was increased under Th1 and Treg polarization but decreased under Th17 polarization. Th17 cell activation-associated genes were possibly increased while Th1 and Treg cell differentiation-associated genes were inhibited by posttranscriptional gene silencing of BATF2 in CD4+ T cells. CONCLUSIONS: BATF2 promoted Th1 and Treg cell differentiation but suppressed Th17 cell activation in anti-MDA5+ CADM.

The TGF-ß/miR-31/CEACAM1-S axis inhibits CD4+ CD25+ Treg differentiation in systemic lupus erythematosus.

Defects causing concomitant loss of CD25 expression in regulatory T cells (Tregs) have been identified in systemic lupus erythematosus (SLE). However, the cause of this deficiency is not fully understood. Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), an immune co-receptor, contributes to general T-cell function and activation. Our previous study revealed that CEACAM1 expression was upregulated in peripheral blood mononuclear cells (PBMCs) from patients with SLE. However, its role remains unclear. Herein, we confirmed CEACAM1, especially CEACAM1-S, was upregulated in PBMCs from patients with SLE. CEACAM1-S over-expression inhibits CD4+ CD25+ Treg differentiation, whereas knockdown of CEACAM1 had the opposite effect in vitro. CEACAM1-S is the target of miR-31. MiR-31 mimic inhibits CEACAM1 expression and enhances CD4+ CD25+ Treg differentiation, which was reversed by CEACAM1-S over-expression. Moreover, the circulating TGF-ß level was upregulated in SLE patients and TGF-ß reduced miR-31 expression via enhancing NF-κB activity. Importantly, CEACAM1 and TGF-ß mRNA levels were downregulated, while the miR-31 level and the abundance of CD4+ CD25+ Tregs were increased in inactive patients compared with that in patients with active SLE. In addition, CEACAM1-S expression was positively correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, while CD4+ CD25+ Treg abundance and miR-31 level were negatively correlated with the SLEDAI score. In conclusion, reduced activity of miR-31 by TGF-ß, via the inhibition of NF-ᴋB, acted to inhibit the differentiation of CD4+ CD25+ Tregs by directly targeting CEACAM1-S and to promote autoimmunity.

Liver X receptor agonist GW3965 protects against sepsis by promoting myeloid derived suppressor cells apoptosis in mice.

AIMS: Immunosuppressive myeloid-derived suppressor cells (MDSCs) continuously expand and lead to poor outcome during sepsis. The activation of liver X receptor (LXR) can mitigate sepsis-induced liver and myocardial damage. This study aims to determine whether LXR plays a protective role in sepsis by regulating MDSCs. MAIN METHODS: Cecal ligation and puncture(CLP)was used to induce sepsis in mice. The mice were then treated with LXR agonist GW3965 (3 mg/kg) or vehicle 1 h, 6 h, 12 h, 24 h, 48 h, 72 h postoperatively. The effect of LXR on the survival rate and multi-organ injury induced by sepsis was evaluated by survival analysis, histological staining, biochemical analysis and ELISAs. The percentages of MDSCs and T cells were detected using flow cytometry. The mRNA expressions of LXR and ATP-binding cassette transporter A1 (ABCA1) were measured using real-time quantitative PCR (RT-qPCR). ABCA1 protein level was determined using immunofluorescence staining. KEY FINDINGS: LXR agonist GW3965 treatment improved the survival of septic mice, accompanied by reduced multi-organ injury and a decreased level of inflammatory cytokines. Furthermore, GW3965 treatment decreased MDSCs abundance in spleen by boosting the apoptosis of spleen MDSCs, therefore ameliorating their immunosuppressive activity. Meanwhile, bacteria clearance in tissues was enhanced after the GW3965 administration in septic mice. Mechanistically, GW3965 activated LXRß and its downstream target ABCA1 to initiate the apoptosis of spleen MDSCs. SIGNIFICANCE: These findings provide new insights into the relationship between LXR and MDSCs in sepsis, thus revealing a potentially effective approach to target the immunosuppression of sepsis.

Comparative study of collagen distribution in the dermis of the embryonic carapace of soft- and hard-shelled cryptodiran turtles.

Turtles are characterized by their typical carapace, which is primarily composed of corneous beta proteins in the horny part and collagen in the dermal part. The formation of the extracellular matrix in the dermis of the carapace in a hard-shelled and a soft-shelled turtle has been compared. The study examines carapace development, with an emphasis on collagen accumulation, in the soft-shelled turtle Pelodiscus sinensis and hard-shelled turtle Trachemys scripta elegans, using comparative morphological and embryological analyses. The histological results showed that collagen deposition in the turtle carapace increased as the embryos developed. However, significant differences were observed between the two turtle species at the developmental stages examined. The microstructure of the dermis of the carapace of P. sinensis showed light and dark banding of collagen bundles, with a higher overall collagen content, whereas the carapacial matrix of T. scripta was characterized by loosely packed and thinner collagenous fiber bundles with a lower percentage of type I collagen. Overall, the formation and distribution of collagen fibrils at specific developmental stages are different between the soft-and hard-shelled turtles. These results indicate that the pliable epidermis of the soft-shelled turtle is supported by a strong dermis that is regularly distributed with collagen and that it allows improved maneuvering, whereas a strong but inflexible epidermis as observed in case of hard-shelled turtles limits movement.

HSF1 Alleviates Microthrombosis and Multiple Organ Dysfunction in Mice with Sepsis by Upregulating the Transcription of Tissue-Type Plasminogen Activator.

Sepsis is a life-threatening complication of infection closely associated with coagulation abnormalities. Heat shock factor 1 (HSF1) is an important transcription factor involved in many biological processes, but its regulatory role in blood coagulation remained unclear. We generated a sepsis model in HSF1-knockout mice to evaluate the role of HSF1 in microthrombosis and multiple organ dysfunction. Compared with septic wild-type mice, septic HSF1-knockout mice exhibited a greater degree of lung, liver, and kidney tissue damage, increased fibrin/: fibrinogen deposition in the lungs and kidneys, and increased coagulation activity. RNA-seq analysis revealed that tissue-type plasminogen activator (t-PA) was upregulated in the lung tissues of septic mice, and the level of t-PA was significantly lower in HSF1-knockout mice than in wild-type mice in sepsis. The effects of HSF1 on t-PA expression were further validated in HSF1-knockout mice with sepsis and in vitro in mouse brain microvascular endothelial cells using HSF1 RNA interference or overexpression under lipopolysaccharide stimulation. Bioinformatics analysis, combined with electromobility shift and luciferase reporter assays, indicated that HSF1 directly upregulated t-PA at the transcriptional level. Our results reveal, for the first time, that HSF1 suppresses coagulation activity and microthrombosis by directly upregulating t-PA, thereby exerting protective effects against multiple organ dysfunction in sepsis.

Space-Time Block Coded Cooperative MIMO Systems.

The main objective of a Cooperative Multiple-Input Multiple-Output (CMIMO) system is to improve network throughput and network coverage and save energy. By grouping wireless devices as virtual multi-antenna nodes, it can thus simulate the functions of multi-antenna systems. A Space-Time Block Code (STBC) was proposed to utilize the spatial diversity of MIMO systems to improve the diversity gain and coding gain. In this paper, we proposed a cooperative strategy based on STBC and CMIMO, which is referred to as Space-Time Block Coded Cooperative Multiple-Input Multiple-Output (STBC-CMIMO) to inherit the advantages from both STBC and CMIMO. The theoretical performance analysis for the proposed STBC-CMIMO is presented. The performance advantages of the STBC-CMIMO are also shown by simulations. In the simulations, it is demonstrated that STBC-CMIMO can obtain significant performance compared with the existing CMIMO system.