Photocatalytic selective oxidation of toluene under encapsulated air conditions.

Benzaldehydes are indispensable building blocks in chemistry. However, the selective oxidation of toluene to benzaldehyde remains an ongoing challenge due to the low oxidation potential of benzaldehyde compared to toluene. We report herein a mild protocol that combines hydrogen atom transfer (HAT) with encapsulated air conditions and suitable catalyst loading for selective oxidation of toluene with high selectivity as well as good functional-group tolerance and a broad substrate scope for the synthesis of various high-value aromatic aldehydes. Moreover, the compatibility of this reaction with toluene derivatives of bioactive molecules further demonstrated the practicality of this approach. Mechanism studies have demonstrated that the collaboration between the oxygen quantity and the HAT catalytic system has a major impact on the high selectivity of the reaction. This study not only showcases the effectiveness of HAT strategies toward selective oxidation of toluene to benzaldehyde, but also provides an approach to controlling the selectivity of HAT reactions.

Enhanced synthesis of chloramphenicol intermediate L-threo-p-nitrophenylserine using engineered L-threonine transaldolase and by-product elimination.

L-threo-p-nitrophenylserine (component 2) is an important intermediate during synthesis of chloramphenicol. However, its biosynthesis is limited by enzyme activity and stereoselectivity. In this study, we achieved a breakthrough in the high-efficiency production of 2 by employing engineered Chitiniphilus shinanonensis L-threonine transaldolase (ChLTTA) in conjunction with a by-product elimination system within a one-pot reaction. Notably, a novel visual stepwise high-throughput screening method was developed for the directed evolution of ChLTTA, leveraging its characteristic color. The engineered mutant F70D/F59A (Mu6 variant) emerged as a star performer, exhibiting a remarkable 2.6-fold increase in catalytic efficiency over the wild-type ChLTTA, coupled with an outstanding 91.5 % diastereoisomer excess (de). Molecular dynamics (MD) simulations unraveled the mechanism responsible for the enhanced catalytic performance observed in the Mu6 variant. Meanwhile, the Mu6 variant was coupled with Saccharomyces cerevisiae ethanol dehydrogenase (ScADH) and Candida boidinii formate dehydrogenase (CbFDH) to create a high-efficiency cascade system (E.coli/pRSF-Mu6-ScADH-CbFDH). Under optimized conditions, this cascade system demonstrated unparalleled performance, yielding 201.5 mM of 2 with an impressive conversion of 95.9 % and a de value of 94.5 %. This achievement represents the highest reported yield to date. This study offers a novel insight into the sustainable and efficient production of chloramphenicol intermediate.

Suramin inhibits phenotypic transformation of vascular smooth muscle cells and neointima hyperplasia by suppressing transforming growth factor beta receptor 1 /Smad2/3 pathway activation.

Vascular smooth muscle cells (VSMCs) contribute to neointimal hyperplasia (NIH) after vascular injury, a common feature of vascular remodelling disorders. Suramin is known to exert antitumour effects by inhibiting the proliferation of various tumour cells; however, its effects and mechanism on VSMCs remain unclear. This study investigated the effects of suramin on human aortic smooth muscle cells (HASMCs), rat aortic smooth muscle cells (RASMCs) and NIH to examine its suitability for the prevention of vascular remodelling disorders. In vitro, suramin administration reduced platelet-derived growth factor type BB (PDGF-BB)-stimulated proliferation, migration, and dedifferentiation of VSMCs through a transforming growth factor beta receptor 1 (TGFBR1)/Smad2/3-dependent pathway. Suramin dramatically inhibited NIH ligation in the left common carotid artery (LCCA) vivo. Therefore, our results indicate that suramin protects against the development of pathological vascular remodelling by attenuating VSMCs proliferation, migration, and phenotypic transformation and may be used as a potential medicine for the treatment of NIH.

Aroma Compound Changes in the Jiangxiangxing Baijiu Solid-State Distillation Process: Description, Kinetic Characters and Cut Point Selection.

Solid-state distillation is a distinctive process for extracting the baijiu aroma compounds that determine the flavor character of baijiu. In this study, the changes in various chemical properties of the aroma compounds in three classical Jiangxiangxing baijiu fermented grain distillation processes were analyzed. The changes in the aroma compounds in the instantaneous distillates were quantified and correlation analyzes were conducted. The results showed that the effect of the aroma compounds was greater than the differences between the fermented grains. Eleven representative aroma compounds were selected to develop the kinetic models describing two opposing changes. For the regulation of the Jiangxiangxing baijiu aroma compounds, their recovery rates were calculated using a kinetic model. A comprehensive comparison of the recovery rates of the characteristic aroma and other aroma compounds at different cut-off values revealed that the optimum recovery rate of the characteristic aroma of Jiangxiangxing baijiu 2,3,5,6-tetramethylpyrazine was 14.53% at cut-off values of 3.9 and 19.8 min. In this study, representative changes in the aroma compounds and the selection of cut-off values to regulate the baijiu distillation aroma were proposed.

Association between Troponin Elevation and Decreased Myocardial Blood Flow Reserve in Patients without Obstructive Coronary Artery Disease.

INTRODUCTION: To study the prognostic factors of patients with chest pain and without obstructive coronary artery disease is of great significance for the management of such patients. We assessed whether a high-sensitivity troponin I (hs-TnI) is associated with prognosis in patients with chest pain and without obstructive coronary artery disease. METHODS: From 2011 to 2017, 489 consecutively hospitalized patients with chest pain and without significant coronary artery stenosis (<50%) were tested for hs-TnI and underwent stress myocardial contrast echocardiography (MCE). Myocardial blood flow reserve (MBFR) was measured by stress MCE. Patients were followed (median, 41 months) for composite endpoints, including cardiovascular death and non-fatal myocardial infarction. Cox proportional hazards models were performed to determine associations between hs-TnI and the composite endpoints. RESULTS: Among 489 patients with chest pain and without significant coronary artery stenosis, 257 patients (52.6%) had elevated hs-TnI. Compared to patients with normal hs-TnI, patients with elevated hs-TnI were older (p = 0.013) and had a higher prevalence of atrial fibrillation (p = 0.003), higher left ventricular mass index (p = 0.002) and E/e' septal (p < 0.001), and a lower MBFR (p < 0.001). After adjustment, there was still a significant association between hs-TnI and MBFR (odds ratio = 1.145; 95% confidence interval [CI], 1.079-1.214; p < 0.001). Compared with patients with normal hs-TnI, patients with elevated hs-TnI had a greater cumulative event rate (log-rank p = 0.002). Males (hazard ratio [HR], 4.770; 95% CI, 1.175-19.363; p = 0.029) and reduced MBFR (HR, 2.496; 95% CI, 1.446-4.311; p = 0.001) were risk factors associated with composite endpoints in patients with elevated hs-TnI. CONCLUSIONS: In patients with chest pain and without obstructive coronary artery disease, elevated hs-TnI is associated with decreased myocardial perfusion by contrast echocardiography as well as a higher incidence of cardiovascular events.

Nitrogen-doped Carbon Dots as Efficient Photocatalysts for High Selectivity of Dehalogenative Oxyalkylation of Styrene.

Carbon dots (CDs) are a type of carbon-based luminescent material with a zero-dimensional structure and a size of less than 10 nm, which are composed of sp2/sp3 hybrid carbon nuclei and surface functional groups. Because CDs has strong photoluminescence and good light absorption in the ultraviolet and near visible regions, it is an excellent candidate for photocatalytic applications. However, the use of nonmetallic doped CDs as photosensitizers for direct photocatalytic organic reactions has been limited to several scattered reports. Herein, we present nitrogen-doped carbon dots (N-CDs) that has a capability for not only produce reactive oxygen species (ROS), including superoxide anion radical (O2⋅-) and singlet oxygen (1O2), but also provide an unprecedented high activity of dehalogenative oxyalkylation of styrene with a yield of 93 %. This work develops a novel opportunity to utilize cost-effective and easily accessible CDs for the advancement of photocatalysis.

Rational Design of l-Threonine Transaldolase-Mediated System for Enhanced Florfenicol Intermediate Production.

l-threo-p-methylsulfonylphenylserine (compound 1b) is the main intermediate of florfenicol, and its efficient synthesis has been the subject of current research. Herein, Burkholderia diffusa l-threonine transaldolase (BuLTTA) was rationally designed based on the sequence-structure-function relationship. A mutant M4 (Asn35Ser/Thr352Asn) could produce 35.5 mM 1b with 88.8% conversion and 93.8% diastereoselectivity, 314 and 129% of the values observed for wild-type BuLTTA. Molecular dynamics simulations indicated that the shortened distance between key active site residues and the transition state (PLP-1b) and the improved hydrogen bond force enhanced the catalytic performance of the M4 variant. Then, the mutant M4 was combined with K. kurtzmanii alcohol dehydrogenase (KkADH) to eliminate the BuLTTA-inhibiting byproduct acetaldehyde, and a cosubstrate was added to regenerate the ADH cofactor NADH. Under optimized conditions, the yield of 1b reached 115.2 mM with a conversion of 96% and a diastereoselectivity of 95.5%. This work provides a new strategy for the efficient and sustainable production of 1b.

Biomimetic, knittable aerogel fiber for thermal insulation textile.

Aerogels have been considered as an ideal material for thermal insulation. Unfortunately, their application in textiles is greatly limited by their fragility and poor processability. We overcame these issues by encapsulating the aerogel fiber with a stretchable layer, mimicking the core-shell structure of polar bear hair. Despite its high internal porosity over 90%, our fiber is stretchable up to 1000% strain, which is greatly improved compared with that of traditional aerogel fibers (~2% strain). In addition to its washability and dyeability, our fiber is mechanically robust, retaining its stable thermal insulation property after 10,000 stretching cycles (100% strain). A sweater knitted with our fiber was only one-fifth as thick as down, with similar performance. Our strategy for this fiber provides rich possibilities for developing multifunctional aerogel fibers and textiles.

Establishment and validation of a nomogram model for riskprediction of hepatic encephalopathy: a retrospective analysis.

To establish a high-quality, easy-to-use, and effective risk prediction model for hepatic encephalopathy, to help healthcare professionals with identifying people who are at high risk of getting hepatic encephalopathy, and to guide them to take early interventions to reduce the occurrence of hepatic encephalopathy. Patients (n = 1178) with decompensated cirrhosis who attended the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were selected for the establishment and validation of a nomogram model for risk prediction of hepatic encephalopathy. In this study, we screened the risk factors for the development of hepatic encephalopathy in patients with decompensated cirrhosis by univariate analysis, LASSO regression and multifactor analysis, then established a nomogram model for predicting the risk of getting hepatic encephalopathy for patients with decompensated cirrhosis, and finally performed differentiation analysis, calibration analysis, clinical decision curve analysis and validation of the established model. A total of 1178 patients with decompensated cirrhosis who were hospitalized and treated at the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were included for modeling and validation. Based on the results of univariate analysis, LASSO regression analysis and multifactor analysis, a final nomogram model with age, diabetes, ascites, spontaneous peritonitis, alanine transaminase, and blood potassium as predictors of hepatic encephalopathy risk prediction was created. The results of model differentiation analysis showed that the AUC of the model of the training set was 0.738 (95% CI 0.63-0.746), while the AUC of the model of the validation set was 0.667 (95% CI 0.541-0.706), and the two AUCs indicated a good discrimination of this nomogram model. According to the Cut-Off value determined by the Jorden index, when the Cut-Off value of the training set was set at 0.150, the sensitivity of the model was 72.8%, the specificity was 64.8%, the positive predictive value was 30.4%, and the negative predictive value was 91.9%; when the Cut-Off value of the validation set was set at 0.141, the sensitivity of the model was 69.7%, the specificity was 57.3%, the positive predictive value was 34.5%, and the negative predictive value was 84.7%. The calibration curve and the actual events curve largely overlap at the diagonal, indicating that the prediction with this model has less error. The Hosmer-Lemeshow test for goodness of fit was also applied, and the results showed that for the training set, χ2 = 1.237587, P = 0.998, and for the validation set, χ2 = 31.90904, P = 0.0202, indicating that there was no significant difference between the predicted and actual observed values. The results of the clinical decision curve analysis showed that the model had a good clinical benefit, compared with the two extreme clinical scenarios (all patients treated or none treated), and the model also had a good clinical benefit in the validation set. This study showed that aged over 55 years, complications of diabetes, ascites, and spontaneous bacterial peritonitis, abnormal glutamate aminotransferase and abnormal blood potassium are independent risks indicators for the development of hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model based on the indicators mentioned above can effectively and conveniently predict the risk of developing hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model established on this study can help clinical healthcare professionals to timely and early identify patients with high risk of developing hepatic encephalopathy.

Host-Guest Photosensitizer of a Cationic BODIPY Derivative and Cucurbit[7]uril for High-Efficiency Visible Light-Induced Photooxidation Reactions.

In recent years, there has been a notable surge of interest in the fields of organic and pharmaceutical research about photocatalysts (PCs) and photosensitizers (PSs). In this study, a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) molecule adorned with quaternary ammonium (TMB) functionality was meticulously designed and synthesized. This compound has remarkable characteristics such as exceptional water solubility, great optical qualities, and commendable photostability. It can form a 1:1 complex (TMB-CB[7]) with cucurbit[7]uril (CB[7]) through host-guest interactions in the aqueous solution and shows obvious fluorescence enhancement. The reactive oxygen species (ROS) including superoxide anion radical (O2·-) and singlet oxygen (1O2) generation ability of TMB-CB[7] were promoted compared with that of TMB in the aqueous solution. More interestingly, the ROS generated from TMB-CB[7] can be used as PCs for aerobic cross dehydrogenation coupling reactions and photooxidation reactions in water with high yields of 89 and 95%, respectively. Therefore, the utilization of a host-guest PS presents a novel and environmentally friendly approach for conducting photocatalyzed organic processes under ambient conditions using visible light.

Construction of an efficient artificial light-harvesting system based on hyperbranched polyethyleneimine and improvement of photocatalytic performance.

An artificial light-harvesting system (ALHS) was developed in aqueous solution by employing the electrostatic co-assembly of a tetraphenylethylene derivative modified with two sulfonate groups (TPE-BSBO) and hyperbranched polyethyleneimine (PEI) as the energy donors, and 4,7-bis(2-thienyl)-2,1,3-benzothiadiazole (DBT) as the energy acceptors. The ALHS exhibits not only high efficiency in energy transfer and conversion but also a significant enhancement in the generation of reactive oxygen species (ROS), especially superoxide anion radicals (O2˙-), facilitating its utilization in photocatalytic oxidation reactions.

Novel mechanism of hydrogen peroxide for promoting efficient natamycin synthesis in Streptomyces.

The mechanism of regulation of natamycin biosynthesis by Streptomyces in response to oxidative stress is unclear. Here, we first show cholesterol oxidase SgnE, which catalyzes the formation of H2O2 from sterols, triggered a series of redox-dependent interactions to stimulate natamycin production in S. gilvosporeus. In response to reactive oxygen species, residues Cys212 and Cys221 of the H2O2-sensing consensus sequence of OxyR were oxidized, resulting in conformational changes in the protein: OxyR extended its DNA-binding domain to interact with four motifs of promoter p sgnM . This acted as a redox-dependent switch to turn on/off gene transcription of sgnM, which encodes a cluster-situated regulator, by controlling the affinity between OxyR and p sgnM , thus regulating the expression of 12 genes in the natamycin biosynthesis gene cluster. OxyR cooperates with SgnR, another cluster-situated regulator and an upstream regulatory factor of SgnM, synergistically modulated natamycin biosynthesis by masking/unmasking the -35 region of p sgnM depending on the redox state of OxyR in response to the intracellular H2O2 concentration. IMPORTANCE Cholesterol oxidase SgnE is an indispensable factor, with an unclear mechanism, for natamycin biosynthesis in Streptomyces. Oxidative stress has been attributed to the natamycin biosynthesis. Here, we show that SgnE catalyzes the formation of H2O2 from sterols and triggers a series of redox-dependent interactions to stimulate natamycin production in S. gilvosporeus. OxyR, which cooperates with SgnR, acted as a redox-dependent switch to turn on/off gene transcription of sgnM, which encodes a cluster-situated regulator, by masking/unmasking its -35 region, to control the natamycin biosynthesis gene cluster. This work provides a novel perspective on the crosstalk between intracellular ROS homeostasis and natamycin biosynthesis. Application of these findings will improve antibiotic yields via control of the intracellular redox pressure in Streptomyces.

Construction of aggregation-induced emission photosensitizers through host-guest interactions for photooxidation reaction and light-harvesting.

In the present work, we have designed and synthesized a triphenylamine modified cyanophenylenevinylene derivative (TPCI), which can self-assembly with cucurbit[6]uril (CB[6]) and cucurbit[8]uril (CB[8]) through host-guest interactions to form supramolecular complexes (TPCI-CB[6]) and supramolecular polymers (TPCI-CB[8]) in the aqueous solution. The supramolecular assemblies of TPCI-CB[6] and TPCI-CB[8] not only exhibited high singlet oxygen (1O2) production efficiency as photosensitizers, but also realized the application in the construction of artificial light-harvesting systems due to the excellent fluorescence properties in the aqueous solution. The production efficiency of 1O2 has been effectively improved after the addition of CB[6] and CB[8] for TPCI, which were applied as efficient photosensitizers in the photooxidation reactions of thioanisole and its derivatives with the highest yield of 98% in the aqueous solution. The excellent fluorescence properties of TPCI-CB[6] and TPCI-CB[8] can be used as energy donors in artificial light-harvesting systems with energy acceptors sulforhodamine 101 (SR101) and cyanine dye 5 (Cy5), in which one-step energy transfer processes of TPCI-CB[6]+SR101 and TPCI-CB[8]+Cy5, and a two-step sequential energy transfer process of TPCI-CB[6]+SR101+Cy5 were constructed to simulate the natural photosynthesis system.

Molecular subtypes based on DNA sensors predict prognosis and tumor immunophenotype in hepatocellular carcinoma.

DNA sensors play crucial roles in inflammation and have been indicated to be involved in antitumor or tumorigenesis, while it is still unclear whether DNA sensors have potential roles in the prognosis and immunotherapy of hepatocellular carcinoma (HCC). Herein, The Cancer Genome Atlas and Gene Expression Omnibus databases were used to analyze RNA sequencing data and clinical information. A total of 14 DNA sensors were collected and performed consensus clustering to determine their molecular mechanisms in HCC. Two distinct molecular subtypes (Clusters C1 and C2) were identified and were associated with different overall survival (OS). Immune subtype analysis revealed that C1 was mainly characterized by inflammation, while C2 was characterized by lymphocyte depletion. Immune scoring and immunomodulatory function analysis confirmed the different immune microenvironment of C1 and C2. Notably, significant differences in "Hot Tumor" Immunophenotype were observed between the two subtypes. Moreover, the prognostic model based on DNA sensors is capable of effectively predicting the OS of HCC patients. Besides, the chemotherapeutic drug analysis showed the different sensitivity of two subtypes. Taken together, our study shows that the proposed DNA sensors were a reliable signature to predict the prognosis and immunotherapy response with potential application in the clinical decision and treatment of HCC.

Regulation of the Innate Immune System as a Therapeutic Approach to Supporting Respiratory Function in ALS.

Amyotrophic lateral sclerosis (ALS) is a clinical diagnosis used to define a neurodegenerative process that involves progressive loss of voluntary muscle function and leads to death within 2-5 years after diagnosis, in most cases because of respiratory function failure. Respiratory vital capacity (VC) measurements are reproducible and strong predictors of survival. To understand the role of the innate immune response in progressive VC loss we evaluated ALS clinical trial and biomarker results from a 6-month phase 2 study of NP001, a regulator of innate immune function. All ALS baseline values were similar between treated and controls except for those > 65 years old who were excluded from analysis. Treated patients with plasma CRP ≥ 1.13 mg/L (high CRP) showed a 64% slower rate of VC decline compared with placebo and those with plasma CRP < 1.13 mg/L (low CRP) who showed no response. High CRP patients showed no age associated loss of VC whereas low CRP patients showed an age dependent loss of VC function. Plasma levels of serum amyloid A (SAA) were similarly elevated in high CRP patients consistent with ongoing innate immune activation. Plasma TGFB1 in high CRP treated patients was 95% higher than placebo at 6-months, confirming the activation and release of this anti-inflammatory factor by the innate immune alpha 2 macroglobulin (A2M) system. This report is the first to link a biomarker confirmed regulation of the innate immune system with a therapeutic approach for controlling VC loss in ALS patients.

Discovery of a High-Efficient Algicidal Bacterium against Microcystis aeruginosa Based on Examinations toward Culture Strains and Natural Bloom Samples.

Harmful cyanobacterial blooms occur worldwide and pose a great threat to aquatic ecosystems and public health. The application of algicidal bacteria represents an eco-friendly strategy for controlling harmful cyanobacterial blooms; thus, searching for a high efficiency of algicidal bacteria has been becoming an important and continuous task in science. Herein, we identified a bacterial strain coded Streptomyces sp. HY with a highly algicidal activity, and investigated its algicidal efficiency and mechanism against Microcystis aeruginosa. The strain HY displayed high algicidal activity toward Microcystis aeruginosa cells, with a removal rate of 93.04% within 2 days via indirect attack. Streptomyces sp. HY also showed the ability to lyse several genera of cyanobacterial strains, including Dolichospermum, Pseudanabaena, Anabaena, and Synechocystis, whereas it showed a minor impact on the green alga Scenedesmus obliquus, demonstrating its selectivity specially for targeting cyanobacteria. Its algicidal mechanism involved damages to the photosynthesis system, morphological injury of algal cells, oxidative stress, and dysfunction of the DNA repair system. Furthermore, HY treatment reduced the expression levels of genes (mcyB and mcyD) related to microcystin biosynthesis and decreased the total content of microcystin-leucine-arginine by 79.18%. Collectively, these findings suggested that the algicidal bacteria HY is a promising candidate for harmful cyanobacterial bloom control.

Comprehensive screening strategy coupled with structure-guided engineering of l-threonine aldolase from Pseudomonas putida for enhanced catalytic efficiency towards l-threo-4-methylsulfonylphenylserine.

l-Threonine aldolases (TAs) can catalyze aldol condensation reactions to form ß-hydroxy-α-amino acids, but afford unsatisfactory conversion and poor stereoselectivity at the Cß position. In this study, a directed evolution coupling high-throughput screening method was developed to screen more efficient l-TA mutants based on their aldol condensation activity. A mutant library with over 4000 l-TA mutants from Pseudomonas putida were obtained by random mutagenesis. About 10% of mutants retained activity toward 4-methylsulfonylbenzaldehyde, with five site mutations (A9L, Y13K, H133N, E147D, and Y312E) showing higher activity. Iterative combinatorial mutant A9V/Y13K/Y312R catalyzed l-threo-4-methylsulfonylphenylserine with a 72% conversion and 86% diastereoselectivity, representing 2.3-fold and 5.1-fold improvements relative to the wild-type. Molecular dynamics simulations illustrated that additional hydrogen bonds, water bridge force, hydrophobic interactions, and π-cation interactions were present in the A9V/Y13K/Y312R mutant compared with the wild-type to reshape the substrate-binding pocket, resulting in a higher conversion and Cß stereoselectivity. This study provides a useful strategy for engineering TAs to resolve the low Cß stereoselectivity problem and contributes to the industrial application of TAs.

Construction of artificial light-harvesting systems based on a variety of polyelectrolyte materials and application in photocatalysis.

In the present work, we designed and synthesized a cationic cyano-substituted p-phenylenevinylene derivative (PPTA), which can form supramolecular assemblies through electrostatic interaction with a type of polyelectrolyte material anionic guar gum (GP5A). A polyelectrolyte-based artificial light-harvesting system (LHS) was constructed by selecting a fluorescent dye sulforhodamine 101 (SR101) that matched its energy level as an energy acceptor. The energy harvested by the acceptors was used in the aqueous phase cross dehydrogenation coupling (CDC) reaction with a yield of up to 87%. In addition, the general applicability of polyelectrolyte materials to build artificial LHS was demonstrated by three other polyelectrolyte materials sodium polyphenylene sulfonate (RSS), sodium carboxymethyl cellulose (CMC), and sodium polyacrylate (PAAS), in which the CDC reaction was also carried out by these three LHSs and obtained high yields. This work not only provides a new method to construct LHSs by using polyelectrolyte materials, but also provides a beneficial exploration for further applying the energy harvested in LHSs to the field of photocatalysis in an aqueous solution.

Sonodynamic therapy reduces cardiomyocyte apoptosis through autophagy activated by reactive oxygen species in myocardial infarction.

Myocardial infarction (MI) is lethal to patients because of acute ischemia and hypoxia leading to cardiac tissue apoptosis. Autophagy played a key role in MI through affecting the survival of cardiomyocytes. LncRNA-MHRT (myosin heavy-chain-associated RNA transcripts) was specific to the heart and cardiomyocytes, and inhibition of lncRNA-MHRT transcription under pathological stimuli could cause cardiac hypertrophy and even heart failure (HF). Sonodynamic therapy (SDT) is a new and developing medical technique that utilizes low-intensity ultrasound to locally activate a preloaded sonosensitizer. Our group previously reported that SDT could regulate autophagy. In this study, we investigated whether SDT could reduce MI-induced cardiomyocyte apoptosis via activating autophagy pathway. SDT improved cardiac function and suppresses MI-induced cardiomyocyte apoptosis. SDT alleviated MI-induced cardiomyocyte apoptosis by improving autophagy. MHRT mediated the inhibiting effect of SDT on cardiomyocyte apoptosis via activating autophagy pathway. Our data reveal a novel effect that SDT protects against MI and confirm that SDT reduces MI-induced cardiomyocyte apoptosis via activating MHRT-mediated-autophagy. Thus, our findings also indicate that SDT may be used as a potential method for treatment of post-myocardial infarction heart failure.

Metabolite profiling analysis of hepatitis B virus-induced liver cirrhosis patients with minimal hepatic encephalopathy using gas chromatography-time-of-flight mass spectrometry and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry.

This study used gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) and ultra-performance liquid chromatography-quadrupole TOFMS (UPLC-QTOFMS) metabonomic analytical techniques in combination with bioinformatics and pattern recognition analysis methods to analyze the serum metabolite profiling of hepatitis B virus (HBV)-induced liver cirrhosis patients with minimal hepatic encephalopathy (MHE), to find the specific biomarkers of MHE, to reveal the pathogenesis of MHE, and to determine a promising approach for early diagnosis of MHE. Serum samples of 100 normal controls (NC group), 29 HBV-induced liver cirrhosis patients with MHE (MHE group), and 24 HBV-induced liver cirrhosis patients without MHE [comprising 12 cases of compensated cirrhosis (CS group) and 12 cases of decompensated cirrhosis (DS group)] were collected and employed into GC-TOFMS and UPLC-QTOFMS platforms for serum metabolite detection; the outcome data were then analyzed using principal component analysis and orthogonal partial least squares-discriminant analysis (OPLS-DA). There were no significant differential metabolites between the NC group and the CS group. A series of key differential metabolites were detected. According to the variable influence in projection values and P-values, 60 small-molecule metabolites were considered to be dysregulated in the MHE group (compared to the NC group); 27 of these 60 dysregulated differential metabolites were considered to be the potential biomarkers (see Table 4, marked in bold); 66 small-molecule metabolites were considered to be dysregulated in the DS group (compared to the NC group); 34 of these 66 dysregulated differential metabolites were considered to be the potential biomarkers (see Table 5, marked in bold). According to the fold-change values, 9 of these 27 metabolites, namely valine, oxalic acid, erythro-sphingosine, 4,7,10,13,16,19-docosahexaenoic acid, isoleucine, allo-isoleucine, thyroxine, rac-octanoyl carnitine, and tocopherol (vitamin E), were downregulated in the MHE group (compared to the NC group); the other 18, namely adenine, glycochenodeoxycholic acid, fucose, allothreonine, glycohyocholic acid, glycoursodeoxycholic acid, tyrosine, taurocheno-deoxycholate, phenylalanine, 2-hydroxy-3-methyl-butanoic acid, hydroxyacetic acid, taurocholate, sorbitol, rhamnose, tauroursodeoxycholate, tolbutamide, pyroglutamic acid, and malic acid, were upregulated; 6 of these 34 metabolites were downregulated in the DS group (compared to the NC group), and the other 28 were upregulated, as shown in Table 5. (a) GC-TOFMS and UPLC-QTOFMS metabonomic analytical platforms can detect a range of metabolites in the serum; this might be of great help to study the pathogenesis of MHE and may provide a new approach for the early diagnosis of MHE. (b) Metabonomics analysis in combination with pattern recognition analysis might have great potential to distinguish the HBV-induced liver cirrhosis patients who have MHE from the normal healthy population and HBV-induced liver cirrhosis patients without MHE.