HSPA12A acts as a scaffolding protein to inhibit cardiac fibroblast activation and cardiac fibrosis.

INTRODUCTION: Cardiac fibrosis is the main driver for adverse remodeling and progressive functional decline in nearly all types of heart disease including myocardial infarction (MI). The activation of cardiac fibroblasts (CF) into myofibroblasts is responsible for cardiac fibrosis. Unfortunately, no ideal approach for controlling CF activation currently exists. OBJECTIVES: This study investigated the role of Heat shock protein A12A (HSPA12A), an atypical member of the HSP70 family, in CF activation and MI-induced cardiac fibrosis. METHODS: Primary CF and Hspa12a knockout mice were used in the experiments. CF activation was indicated by the upregulation of myofibroblast characters including alpha-Smooth muscle actin (αSMA), Collagen, and Fibronectin. Cardiac fibrosis was illustrated by Masson's trichrome and picrosirius staining. Cardiac function was examined using echocardiography. Glycolytic activity was indicated by levels of extracellular lactate and the related protein expression. Protein stability was examined following cycloheximide and MG132 treatment. Protein-protein interaction was examined by immunoprecipitation-immunoblotting analysis. RESULTS: HSPA12A displayed a high expression level in quiescent CF but showed a decreased expression in activated CF, while ablation of HSPA12A in mice promoted CF activation and cardiac fibrosis following MI. HSPA12A overexpression inhibited the activation of primary CF through inhibiting glycolysis, while HSPA12A knockdown showed the opposite effects. Moreover, HSPA12A upregulated the protein expression of transcription factor p53, by which mediated the HSPA12A-induced inhibition of glycolysis and CF activation. Mechanistically, this action of HSPA12A was achieved by acting as a scaffolding protein to bind p53 and ubiquitin specific protease 10 (USP10), thereby promoting the USP10-mediated p53 protein stability and the p53-medicated glycolysis inhibition. CONCLUSION: The present study provided clear evidence that HSPA12A is a novel endogenous inhibitor of CF activation and cardiac fibrosis. Targeting HSPA12A in CF could represent a promising strategy for the management of cardiac fibrosis in patients.

2D BA2PbI4 Regulating PbI2 Crystallization to Induce Perovskite Growth for Efficient Solar Cells.

Using seeds to control the crystallization of perovskite film is an effective strategy for achieving high-efficiency perovskite solar cells (PSCs). Owing to their excellent environmental stability brought by their long alkyl chain, n-butylammonium (BA) cations are widely used for fabricating efficient and stable PSCs. However, BA-based 2D perovskite is seldom been investigated as a seed. Here, BA2PbI4 is employed to regulate the crystallization of PbI2, acting as nucleation centers. As a result, porous PbI2 film with high crystallinity is obtained, which allows the realization of perovskite film with preferential crystal orientations of (001) and large grain size of over 2 µm. The corresponding PSC achieves a high power conversion efficiency (PCE) of 24.30% and exhibits satisfactory stability, retaining 91.70% of the initial PCE after 300 h of thermal aging at 85°C.

Interfacial Electron Potential Well Facilitates the Design of Cobalt Phosphide Heterojunctions for Hydrogen Evolution.

The interfacial electron modulation of electrocatalysts is an effective way to realize efficient hydrogen production, which is of great importance for future renewable energy systems. However, systematic theory-guided design of catalysts in heterojunction coupling is lacking. In this work, a multi-level theoretical calculation is performed to screen optimal candidates to form a heterojunction with CoP (101) surface for electrocatalytic hydrogen production. To overcome the weak adsorption of H+ on CoP (101), rational design of electrons potential well at the heterojunction interface can effectively enhance the hydrogen adsorption. All p-type cobalt-based phosphides are considered potential candidates at the beginning. After screening for conductivity, stability, interface matching screening, and ΔGH* evaluation, the CoP/Co2 P-H system is identified to be able to display optimal hydrogen production performance. To verify the theoretical design, CoP, CoP/Co2 P-H, and CoP/Co2 P-O are synthesized and the electrochemical analysis is carried out. The hydrogen evolution reaction (HER) performance is consistent with the prediction. This work utilizes the electron potential well effect and multi-level screening calculations to design highly efficient heterojunction catalysts, which can provide useful theoretical guidance for the rational design of heterojunction-type catalysts.

Improved breast ultrasound tumor classification using dual-input CNN with GAP-guided attention loss.

Ultrasonography is a widely used medical imaging technique for detecting breast cancer. While manual diagnostic methods are subject to variability and time-consuming, computer-aided diagnostic (CAD) methods have proven to be more efficient. However, current CAD approaches neglect the impact of noise and artifacts on the accuracy of image analysis. To enhance the precision of breast ultrasound image analysis for identifying tissues, organs and lesions, we propose a novel approach for improved tumor classification through a dual-input model and global average pooling (GAP)-guided attention loss function. Our approach leverages a convolutional neural network with transformer architecture and modifies the single-input model for dual-input. This technique employs a fusion module and GAP operation-guided attention loss function simultaneously to supervise the extraction of effective features from the target region and mitigate the effect of information loss or redundancy on misclassification. Our proposed method has three key features: (i) ResNet and MobileViT are combined to enhance local and global information extraction. In addition, a dual-input channel is designed to include both attention images and original breast ultrasound images, mitigating the impact of noise and artifacts in ultrasound images. (ii) A fusion module and GAP operation-guided attention loss function are proposed to improve the fusion of dual-channel feature information, as well as supervise and constrain the weight of the attention mechanism on the fused focus region. (iii) Using the collected uterine fibroid ultrasound dataset to train ResNet18 and load the pre-trained weights, our experiments on the BUSI and BUSC public datasets demonstrate that the proposed method outperforms some state-of-the-art methods. The code will be publicly released at https://github.com/425877/Improved-Breast-Ultrasound-Tumor-Classification.

Safety and efficacy of remifentanil-propofol combination on "muscle relaxant-free" general anesthesia for therapeutic endoscopic retrograde cholangiopancreatography: a randomized controlled trial.

OBJECTIVE: To prospectively evaluate the safety and efficacy of a "muscle relaxant-free" general anesthesia using a combination of remifentanil and propofol, compared to propofol-based monitored anesthesia care and conventional general anesthesia during therapeutic endoscopic retrograde cholangiopancreatography (ERCP). METHODS: From September to December 2019, 360 patients scheduled for elective ERCP at the Endoscopy Center of the First Affiliated Hospital of Nanjing Medical University were randomly assigned to three different groups: Group MAC (propofol-based monitored anesthesia care, n=120), Group GA1 (general anesthesia with neuromuscular blocking agents, n=120), or Group GA2 (remifentanil-propofol combination-based muscle relaxant-free general anesthesia, n=120). RESULTS: The results showed that there was a significant difference in intraprocedural cardiopulmonary adverse events among the three groups (Group MAC, 37.5%; Group GA1, 19.2%; Group GA2, 17.5%; P < 0.001). Total time (from patient entry into the Endoscopy Center to departure) and room time (from patient entry into the endoscopy suit to departure) were shorter in Group GA2 and Group MAC compared to Group GA1 (P < 0.001). Additionally, endoscopist satisfaction levels were significantly higher in Group GA1 and Group GA2 compared to Group MAC (P < 0.001). CONCLUSION: The study found that administering propofol-remifentanil combination for "muscle relaxant-free" general anesthesia during therapeutic ERCP was safe and effective. This approach offered greater safety and endoscopist satisfaction than propofol-based monitored anesthesia care, as well as shorter total time and room time than conventional general anesthesia.

HSPA12A controls cerebral lactate homeostasis to maintain hippocampal neurogenesis and mood stabilization.

Mood instability, a subjective emotional state defined as rapid mood oscillations of up and down, is a symptom that occurs in several psychiatric disorders, particularly major depressive disorder and bipolar disorder. Heat shock protein A12A (HSPA12A) shows decreased expression in the brains of schizophrenia patients. However, the causal effects of HSPA12A in any psychiatric disorders are completely unknown. To investigate whether HSPA12A affects mood stability, Hspa12a-knockout mice (Hspa12a-/-) and wild-type (WT) littermates were subjected to tests of open field, forced swimming, elevated plus maze, and sucrose preference. Cerebral lactate levels were measured in cerebrospinal fluid (CSF). Adult hippocampal neurogenesis (AHN) was assessed by BrdU labeling. We found that acute mood stress increased hippocampal HSPA12A expression and CSF lactate levels in mice. However, Hspa12a-/- mice exhibited behaviors of mood instability (anhedonia, lower locomotor activity, antidepression, and anxiety), which were accompanied by impaired AHN, decreased CSF lactate levels, and downregulated hippocampal glycolytic enzyme expression. By contrast, HSPA12A overexpression increased lactate production and glycolytic enzyme expression of primary hippocampal neurons. Intriguingly, lactate administration alleviated the mood instability and AHN impairment in Hspa12a-/- mice. Further analyses revealed that HSPA12A was necessary for sustaining cerebral lactate homeostasis, which could be mediated by inhibiting GSK3ß in hippocampal neurons, to maintain AHN and mood stabilization. Taken together, HSPA12A is defined as a novel regulator of mood stability and exerts therapeutic potential for mood disorder. Our findings establish a framework for determining mood disorder and AHN relevance of cerebral lactate homeostasis. HSPA12A is a novel mood stabilizer through inhibiting GSK3ß in hippocampal neurons, thereby sustaining glycolysis-generated lactate to maintain cerebral lactate homeostasis, which ultimately leading to maintenance of hippocampal neurogenesis and mood stabilization.

Enhancing Mechanical Properties of 3D Printing Metallic Lattice Structure Inspired by Bambusa Emeiensis.

Metallic additive manufacturing process parameters, such as inclination angle and minimum radius, impose constraints on the printable lattice cell configurations in complex components. As a result, their mechanical properties are usually lower than their design values. Meanwhile, due to unavoidable process constraints (e.g., additional support structure), engineering structures filled with various lattice cells usually fail to be printed or cannot achieve the designed mechanical performances. Optimizing the cell configuration and printing process are effective ways to solve these problems, but this is becoming more and more difficult and costly with the increasing demand for properties. Therefore, it is very important to redesign the existing printable lattice structures to improve their mechanical properties. In this paper, inspired by the macro- and meso-structures of bamboo, a bionic lattice structure was partitioned, and the cell rod had a radius gradient, similar to the macro-scale bamboo joint and meso-scale bamboo tube, respectively. Experimental and simulated results showed that this design can significantly enhance the mechanical properties without adding mass and changing the printable cell configuration. Finally, the compression and shear properties of the Bambusa-lattice structure were analyzed. Compared with the original scheme, the bamboo lattice structure design can improve the strength by 1.51 times (ß=1.5). This proposed strategy offers an effective pathway to manipulate the mechanical properties of lattice structures simultaneously, which is useful for practical applications.

Predictive value of NoSAS questionnaire combined with the modified Mallampati grade for hypoxemia during routine sedation for gastrointestinal endoscopy.

BACKGROUND: The incidence of hypoxemia during painless gastrointestinal endoscopy remains a matter of concem. To date, there is no recognized simple method to predict hypoxemia in digestive endoscopic anesthesia. The NoSAS (neck circumference, obesity, snoring, age, sex) questionnaire, an objective and simple assessment scale used to assess obstructive sleep apnea (OSA), combined with the modified Mallampati grade (MMP), may have certain screening value. This combination may allow anesthesiologists to anticipate, manage, and consequently decrease the occurrence of hypoxemia. METHODS: This study was a prospective observational trial. The primary endpoint was the incidence of hypoxaemia defined as pulse oxygen saturation (SpO2) < 95% for 10 s. A total of 2207 patients admitted to our hospital for painless gastrointestinal endoscopy were studied. All patients were measured for age, height, weight, body mass index, neck circumference, snoring, MMP, and other parameters. Patients were divided into hypoxemic and non-hypoxemic groups based on the SpO2. The ROC curve was plotted to evaluate the screening value of the NoSAS questionnaire separately and combined with MMP for hypoxemia. The total NoSAS score was evaluated at cut-off points of 8 and 9. RESULTS: With a NoSAS score ≥ 8 as the critical value for analysis, the sensitivity for hypoxemia was 58.3%, the specificity was 88.4%, and the area under the ROC was 0.734 (P < 0.001, 95% CI: 0.708-0.759). With a NoSAS score ≥ 9 as a critical value, the sensitivity for hypoxemia was 36.50%, the specificity rose to 96.16%, and the area under the ROC was 0.663 (P < 0.001, 95% CI: 0.639-0.688). With the NoSAS Score combined with MMP for analysis, the sensitivity was 78.4%, the specificity was 84%, and the area under the ROC was 0.859 (P < 0.001, 95%CI:0.834-0.883). CONCLUSIONS: As a new screening tool, the NoSAS questionnaire is simple, convenient, and useful for screening hypoxemia. This questionnaire, when paired withMMP, is likely to be helpful for the screening of hypoxemia.

CPNE8 Promotes Gastric Cancer Metastasis by Modulating Focal Adhesion Pathway and Tumor Microenvironment.

Little is known about the oncogenic role or biological function of copine Ⅷ (CPNE8) in gastric cancer (GC). Based on TCGA database, we screened for CPNE8 and analyzed the expression of CPNE8 in GC. The correlations between CPNE8 and clinical features were analyzed using TCGA and GEO databases. The prognostic value of CPNE8 was assessed using Cox analysis and Kaplan-Meier curves. The results showed that increased expression of CPNE8 was positively correlated with metastasis and can be considered an independent prognostic risk factor for poor survival. We found that CPNE8 can promote cell proliferation, migration, and invasiveness in GC using in vitro and in vivo experiments. Our study demonstrated that CPNE8 promotes tumor progression via regulation of focal adhesion, and these effects can be rescued by focal adhesion kinase (FAK) inhibitor GSK2256098 or knockdown of FAK. In addition, CPNE8 was correlated significantly with the infiltration of cancer-associated fibroblasts and immune cells, as demonstrated by various algorithms, and high CPNE8 expression predicted poor efficacy of immune checkpoint therapy. Our findings suggest that CPNE8 modulates focal adhesion and tumor microenvironment to promote GC progression and invasiveness and could serve as a novel prognostic biomarker in GC.

GFPT1 promotes the proliferation of cervical cancer via regulating the ubiquitination and degradation of PTEN.

Cervical cancer demonstrates the fourth incidence and death rate in females worldwide. Glutamine--fructose-6-phosphate transaminase 1 (GFPT1), the first rate-limited enzyme of the hexosamine biosynthesis pathway, has been reported to promote the progression of cancers. However, the prognostic value and roles of GFPT1 in cervical cancer are largely unknown. Transcription expression data for cervical cancer were downloaded from public databases. GFPT1 overexpressed and knockdown cell lines were constructed. Colony formation assays, Edu assays and 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were used to measure the proliferation capabilities of cervical cancer cells. Western blot, Immunofluorescence and co-immunoprecipitation assays were performed to verify the interaction between GFPT1and Phosphatase and tensin homolog (PTEN). Animal assays were applied to verify the results in vivo. GFPT1 expression was higher in cervical cancer cell lines. The proliferation capabilities of cervical cancer cells were suppressed in GFPT1 knockdown cells and GFPT1 inhibitor L-DON treated cells. And overexpression of GFPT1 promoted cell proliferation. PTEN was up-regulated in GFPT1 knockdown cells and downregulated in GFPT1 overexpression cells. Immunofluorescence and co-immunoprecipitation results showed that GFPT1 was co-localized and interacted with PTEN. GFPT1 promoted the ubiquitination and degradation of PTEN. Silence of PTEN offsets the growth inhibition of cervical cancer caused by GFPT1 knockdown. Animal assays showed that GFPT1 promoted the proliferation of cervical cancer in vivo. Our study revealed that GFPT1 could promote the progression of cervical cancer by regulating PTEN expression. Our study highlights the GFPT1-PTEN regulation as a potential therapy target for cervical cancer. .

Exploring the cellular landscape of circular RNAs using full-length single-cell RNA sequencing.

Previous studies have demonstrated the highly specific expression of circular RNAs (circRNAs) in different tissues and organisms, but the cellular architecture of circRNA has never been fully characterized. Here, we present a collection of 171 full-length single-cell RNA-seq datasets to explore the cellular landscape of circRNAs in human and mouse tissues. Through large-scale integrative analysis, we identify a total of 139,643 human and 214,747 mouse circRNAs in these scRNA-seq libraries. We validate the detected circRNAs with the integration of 11 bulk RNA-seq based resources, where 216,602 high-confidence circRNAs are uniquely detected in the single-cell cohort. We reveal the cell-type-specific expression pattern of circRNAs in brain samples, developing embryos, and breast tumors. We identify the uniquely expressed circRNAs in different cell types and validate their performance in tumor-infiltrating immune cell composition deconvolution. This study expands our knowledge of circRNA expression to the single-cell level and provides a useful resource for exploring circRNAs at this unprecedented resolution.

Prognosis and Characterization of Immune Microenvironment in Head and Neck Squamous Cell Carcinoma through a Pyroptosis-Related Signature.

Pyroptosis, as a novel identified programmed cell death, is closely correlated with tumor immunity and shows potential roles in cancer treatment. Discerning a pyroptosis-related gene signature and its correlations with tumor immune microenvironment is critical in head and neck squamous cell carcinoma (HNSCC). Transcriptome data and corresponding clinical data were downloaded from TCGA and GEO databases. Tumor mutation burden (TMB) data were obtained from TCGA database. Firstly, univariate and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct a six pyroptosis-related gene signature. Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and principal component analysis (PCA) results verified that the risk model has good performance in predicting the survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the pyroptosis-related gene signature was immune related. Finally, the immune landscape and immunotherapy sensitivity prediction capabilities of the risk model were further explored. There were close correlations between the overall survival (OS) and various immune cells and immune functions. Single-sample gene set enrichment analysis (ssGSEA) showed that high risk group had decreased expression of various immune cells and lower activities of immune functions. Meanwhile, tumor mutation burden (TMB) data combining risk score could well predict the OS of HNSCC patients. However, tumor immune dysfunction and exclusion (TIDE) analysis revealed that there was no significant difference in the sensitivity to immunotherapies between high and low risk groups. Finally, a nomogram based on risk score and clinicopathological parameters was constructed. And, the risk model demonstrated better sensitivity and specificity than TIDE scores and T-cell-inflamed signature (TIS). In conclusion, although the risk model could not well predict the immune escape and response to immunotherapies, the signature established by pyroptosis-related genes, with better sensitivity and specificity than TIDE scores and TIS signature, could be used for predicting prognosis and immune status of HNSCC patients.

Effect of cobalt phosphide (CoP) vacancies on its hydrogen evolution activity via water splitting: a theoretical study.

Defect engineering plays an important role in improving the performance of catalysts. To clarify the roles of Co and P vacancies in CoP for water splitting, a theoretical study based on density functional theory was carried out in this paper. The geometric and electronic structures, activity and stability of the CoP (101)B surface, CoP (101)B with the Co vacancy (Covac) and the P vacancy (Pvac) are investigated. The results indicate that the CoP (101)B surface with Pvac and Covac can enhance the electron transfer to the surface. The Pvac will upward shift the Co d-band center near the vacancy site, which promotes the adsorption of H on the Co atom. As a result, the bridge Co-Co sites near the vacancy become the active sites for the hydrogen evolution reaction (HER) (ΔGH* = 0.01 eV). The loss of the Co atom also results in an upward shift of its d-band center, which will enhance the H adsorption on the adjacent Co sites. The unevenly distributed electrons due to the presence of vacancies on the surface cause spontaneous dissociation of H2O molecules. Furthermore, the thermodynamic analysis and surface energy find that the CoP (101)B and (101)B facets with Covac and Pvac present good stability. The current work has shed light onto the mechanism of water splitting on the surface of phosphide with vacancies. Our study suggests that engineering vacancies on CoP is a feasible route to improve its catalytic activity.

Heat shock protein A12A activates migration of hepatocellular carcinoma cells in a monocarboxylate transporter 4-dependent manner.

Metastasis is responsible for most of the hepatocellular carcinoma (HCC)-associated death. However, its underlying mechanism has yet to be fully elucidated. Glycolysis-derived lactate has been shown to be a powerful regulator of cancer metastasis. Heat shock protein A12A (HSPA12A) encodes a novel member of HSP70 family. We have recently demonstrated that heat shock protein A12A (HSPA12A) inhibited renal cancer cell migration by suppressing lactate output and glycolytic activity, which were mediated by unstabilizing CD147 and promoting its degradation. By striking contrast, here we demonstrated that HSPA12A promoted migration of human HCC cells. Extracellular acidification, lactate export, and glycolytic activity in HCC cells were also promoted following HSPA12A overexpression. Further analysis revealed that HSPA12A interacted with MCT4 and increased its membrane localization, thereby promoting export of lactate generated from glycolysis; this led, ultimately, to HCC cell migration. Our results revealed the opposite effect of HSPA12A on migration of renal cancer cells and that of HCC cells. Of note, in contrast to the inhibitory effect on CD147 expression in renal cancer cells, we found that HSPA12A increased CD147 expression in HCC cells, indicating that the expression of CD147 might exist heterogeneity in different cancer cell types. Taken together, we identified HSPA12A as an activator of HCC migration, a role opposite to that of renal cancer cells. Inhibiting HSPA12A might be a potential therapeutic intervention for HCC metastasis.

circVAMP3 Drives CAPRIN1 Phase Separation and Inhibits Hepatocellular Carcinoma by Suppressing c-Myc Translation.

Previous studies have identified the regulatory roles of circular RNAs (circRNAs) in human cancers. However, the molecular mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unknown. This study screens the expression profile of circRNAs in HCC and identifies circVAMP3 as a significantly downregulated circRNA in HCC tissues. HCC patients with low circVAMP3 expression present poor prognosis. circVAMP3 negatively regulates the proliferation and metastasis of HCC cells in vitro and in vivo by driving phase separation of CAPRIN1 and promoting stress granule formation in cells, which can downregulate the protein level of Myc proto-oncogene protein by inhibiting c-Myc translation. Furthermore, circVAMP3 is widely expressed in many human tissues and is downregulated in related cancers. Therefore, circVAMP3 is a potential prognostic indicator for HCC and may serve as a therapeutic target for HCC treatment.

Recent Progress in Active Mechanical Metamaterials and Construction Principles.

Active mechanical metamaterials (AMMs) (or smart mechanical metamaterials) that combine the configurations of mechanical metamaterials and the active control of stimuli-responsive materials have been widely investigated in recent decades. The elaborate artificial microstructures of mechanical metamaterials and the stimulus response characteristics of smart materials both contribute to AMMs, making them achieve excellent properties beyond the conventional metamaterials. The micro and macro structures of the AMMs are designed based on structural construction principles such as, phase transition, strain mismatch, and mechanical instability. Considering the controllability and efficiency of the stimuli-responsive materials, physical fields such as, the temperature, chemicals, light, electric current, magnetic field, and pressure have been adopted as the external stimuli in practice. In this paper, the frontier works and the latest progress in AMMs from the aspects of the mechanics and materials are reviewed. The functions and engineering applications of the AMMs are also discussed. Finally, existing issues and future perspectives in this field are briefly described. This review is expected to provide the basis and inspiration for the follow-up research on AMMs.

Downregulation of HSPA12A underlies myotoxicity of local anesthetic agent bupivacaine through inhibiting PGC1α-mediated mitochondrial integrity.

Local anesthetics (LAs) are widely used for intraoperative anesthesia and postoperative analgesia. However, LAs (e.g. Bupivacaine) can evoke myotoxicity that closely associated to mitochondrial damage. PGC1a is a mast co-factor for mitochondrial quality control. We have recently demonstrated that PGC1a can be activated by HSPA12A in hepatocytes, suggesting a possibility that HSPA12A protects from LAs myotoxicity through activating PGC1α-mediated mitochondrial integrity. Here, we reported that HSPA12A was downregulated during Bupivacaine-induced myotoxicity in skeletal muscles of mice in vivo and C2c12 myoblast cultures in vitro. Intriguingly, overexpression of HSPA12A attenuated the Bupivacaine-induced C2c12 cell death. We also noticed that the Bupivacaine-induced decrease of glucose consumption and ATP production was improved by HSPA12A overexpression. Moreover, overexpression of HSPA12A in C2c12 cells attenuated the Bupivacaine-induced decrease of mitochondrial contents and increase of mitochondrial fragmentation. The Bupivacaine-induced reduction of PGC1α expression and nuclear localization was markedly attenuated by HSPA12A overexpression. Importantly, pretreatment with a selective PGC1α inhibitor (SR-18292) abolished the protection of HSPA12A from Bupivacaine-induced death and mitochondrial loss in C2c12 cells. Altogether, the findings indicate that downregulation of HSPA12A underlies myotoxicity of Local anesthetic agent Bupivacaine through inhibiting PGC1α-mediated Mitochondrial Integrity. Thus, HSPA12A might represent a viable strategy for preventing myotoxicity of LAs.

Identification of interacting proteins of Arabidopsis cyclophilin38 (AtCYP38) via multiple screening approaches reveals its possible broad functions in chloroplasts.

AtCYP38, a thylakoid lumen localized immunophilin, is found to be essential for photosystem II assembly and maintenance, but how AtCYP38 functions in chloroplast remains unknown. Based on previous functional studies and its crystal structure, we hypothesize that AtCYP38 should function via binding its targets or cofactors in the thylakoid lumen. To identify potential interacting proteins of AtCYP38, we first adopted ATTED-II and STRING web-tools, and found 12 proteins functionally related to AtCYP38. We then screened a yeast two-hybrid library including an Arabidopsis genome wide cDNA with different domain of AtCYP38, and five thylakoid lumen-localized targets were identified. In order to specifically search interacting proteins of AtCYP38 in the thylakoid lumen, we generated a yeast two-hybrid mini library including the thylakoid lumenal proteins and lumenal fractions of thylakoid membrane proteins, and we obtained six thylakoid membrane proteins and nine thylakoid lumenal proteins as interacting proteins of AtCYP38. The interactions between AtCYP38 and several potential targets were further confirmed via pull-down and co-immunoprecipitation assays. Together, a couple of new potential candidate interacting proteins of AtCYP38 were identified, and the results will lay a foundation for unveiling the regulatory mechanisms in photosynthesis by AtCYP38.

Response of seated human subject to ship structure motion caused by the combined effect of shock wave and bubble pulsation.

Underwater explosion (UNDEX) can cause severe damage to hull structure, equipment and human. In this paper, the effect of UNDEX load, including shock wave and bubble pulsation, on seated human response was investigated. The incident pressure of non-contact UNDEX was calculated. A lumped parameter interaction model of the ship structure (single-deck and multi-deck) and seated human was created based on the Taylor's theory and its veracity was verified. The results indicated that the pelvis, which is in direct contact with the structure, is the most vulnerable part of seated human when suffered impact. The shock wave and bubble pulsation had equal destructive potential to upper torso, viscera and head. The low pass filtering feature of multi-deck configuration may magnify the human response caused by the upper deck motion. The energy carried by the low and high frequency component was the dominant factors to human injury and the broadband protection to human shock isolation design is essential.

The Effectiveness and Safety of Intravenous Dexmedetomidine of Different Concentrations Combined with Butorphanol for Post-Caesarean Section Analgesia: A Randomized Controlled Trial.

PURPOSE: The present study aimed to determine the effectiveness of intravenous dexmedetomidine of different concentrations and to evaluate its maternal and neonatal safety when combined with butorphanol in parturients undergoing cesarean section. PATIENTS AND METHODS: A total of 114 parturients between 24 and 43 years of age, with singleton pregnancy who underwent elective cesarean section under epidural anesthesia, were randomly allocated to four groups: group C received 0.9% sodium chloride after delivery, followed by butorphanol (3 µg·kg-1·h-1); patients in groups D1, D2, and D3 received 0.5 µg·kg-1·h-1 dexmedetomidine after delivery, followed by butorphanol (3 µg·kg-1·h-1) combined with dexmedetomidine 0.03, 0.05, and 0.08 µg·kg-1·h-1, respectively. The primary outcome was the visual analogue scale (VAS) score at 6 h after delivery when patients were at rest. Secondary outcome measures included VAS after delivery when patients were on movement and uterine cramping, Ramsay sedation scale (RSS), relative infant dose (RID) of dexmedetomidine, satisfaction with analgesia after surgery and symptoms of CNS depression in neonates. RESULTS: There were no significant differences in patient characteristics among the groups (P > 0.05). The VAS at all timepoints after delivery in groups D2 and D3 were significantly lower than in groups C and D1 (P < 0.001). RSS scores were clearly higher in group D3 than in the other three groups at 6 h and 12 h (P < 0.0001). RID in groups D1, D2, and D3 was 0.171%, 0.197%, and 0.370%, respectively. Compared with group D1, RID was higher in group D3 (P = 0.0079). Degree of satisfaction with analgesia was higher in groups D2 and D3 (P < 0.005). CONCLUSION: Continuous intravenous infusion of 0.05 µg·kg-1·h-1 dexmedetomidine combined with 3 µg·kg-1·h-1 butorphanol could be safely applied in healthy parturients with satisfactory analgesia after cesarean section without changes in sedation.