Reversing the immunosuppressive microenvironment with reduced redox level by microwave-chemo-immunostimulant Ce-Mn MOF for improved immunotherapy.

BACKGROUNDS: Reversing the immunosuppressive tumor microenvironment (TME) in the tumor is widely deemed to be an effective strategy to improve immune therapy. In particular, the redox balance in TME needs to be well controlled due to its critical role in mediating the functions of various cells, including cancer cells and immune-suppressive cells. RESULTS: Here, we propose an efficient strategy to reshape the redox homeostasis to reverse immunosuppressive TME. Specifically, we developed a microwave-chemo-immunostimulant CMMCP to promote the infiltration of the tumor-T cells by simultaneously reducing the reactive oxygen species (ROS) and glutathione (GSH) and improving the oxygen (O2) levels in TME. The CMMCP was designed by loading chemotherapy drugs cisplatin into the bimetallic Ce-Mn MOF nanoparticles coated with polydopamine. The Ce-Mn MOF nanoparticles can effectively improve the catalytic decomposition of ROS into O2 under microwave irradiation, resulting in overcoming hypoxia and limited ROS generation. Besides, the activity of intracellular GSH in TME was reduced by the redox reaction with Ce-Mn MOF nanoparticles. The reprogrammed TME not only boosts the immunogenic cell death (ICD) induced by cisplatin and microwave hyperthermia but also gives rise to the polarization of pro-tumor M2-type macrophages to the anti-tumor M1-type ones. CONCLUSION: Our in vivo experimental results demonstrate that the microwave-chemo-immunostimulant CMMCP significantly enhances the T cell infiltration and thus improves the antitumor effect. This study presents an easy, safe, and effective strategy for a whole-body antitumor effect after local treatment.

An Exergoeconomic Analysis of a Gas-Type Industrial Drying System of Black Tea.

The performance evaluation and optimization of an energy conversion system design of an energy intensive drying system applied the method of combining exergy and economy is a theme of global concern. In this study, a gas-type industrial drying system of black tea with a capacity of 100 kg/h is used to investigate the exergetic and economic performance through the exergy and exergoeconomic methodology. The result shows that the drying rate of tea varies from the maximum value of 3.48 gwater/gdry matter h to the minimum 0.18 gwater/gdry matter h. The highest exergy destruction rate is found for the drying chamber (74.92 kW), followed by the combustion chamber (20.42 kW) in the initial drying system, and 51.83 kW and 21.15 kW in the redrying system. Similarly, the highest cost of the exergy destruction rate is found for the drying chamber (18.497 USD/h), followed by the combustion chamber (5.041 USD/h) in the initial drying system, and 12.796 USD/h and 5.222 USD/h in the redrying system. Furthermore, we analyzed the unit exergy rate consumed and the unit exergy cost of water removal in different drying sections of the drying system, and determined the optimal ordering of each component. These results mentioned above indicate that, whether from an energy or economic perspective, the component improvements should prioritize the drying chamber. Accordingly, minimizing exergy destruction and the cost of the exergy destruction rate can be considered as a strategy for improving the performance of energy and economy. Overall, the main results provide a more intuitive judgment for system improvement and optimization, and the exergy and exergoeconomic methodology can be commended as a method for agricultural product industrial drying from the perspective of exergoeconomics.

Morphological and metabolic changes in an aged strain of Agaricus bisporus As2796.

Agaricus bisporus is the most widely cultivated edible mushroom in the world. Strain quality has an important influence on the yield of A. bisporus, with strains that exhibit aging being a common problem during cultivation. However, little is known about the aging mechanisms of A. bisporus strain. In this study, the normal A. bisporus As2796 strain was compared to the aging A. bisporus As2796Y strain (which was previously discovered during cultivation). In the aging As2796Y mycelia, the mycelial growth rate and fruiting body yield were decreased and the chitin level and cell wall thickness were increased. Additionally, intracellular vacuoles increased, there was cytoplasmic shrinkage, and the sterol level which stabilizes the cell membrane decreased, which led to cytoplasmic outflow and the exudation of a large amount of yellow water from the mycelia. Additionally, there was increased electrolyte leakage. Furthermore, gas chromatography-mass spectrometry (GC/MS) was used to profile the metabolic changes in the aging As2796Y mycelia compared to the normal As2796 mycelia. A total of 52 differential metabolites were identified (75% were downregulated and 25% were upregulated in As2796Y). The reduction of many metabolites decreased the mycelial viability and the ability to maintain cell stability. Overall, this study is the first to report on the morphologic and metabolic changes in aged A. bisporus mycelia, which will aid future research on the mechanisms underlying A. bisporus mycelial aging.Key points• Aging of Agaricus bisporus strains will greatly reduce the fruiting body yield.• Aging of Agaricus bisporus strains can significantly change the cell structure of mycelia.• Many metabolites in the mycelium of aging spawn As2796Y significantly changed.

Fabrication and Performance of Graphene Flexible Pressure Sensor with Micro/Nano Structure.

Laser-induced graphene (LIG) has been widely used in flexible sensors due to its excellent mechanical properties and high conductivity. In this paper, a flexible pressure sensor prepared by bionic micro/nanostructure design and LIG mass fraction regulation is reported. First, prepared LIG and conductive carbon paste (CCP) solutions were mixed to obtain a conductive polymer. After the taro leaf structure was etched on the surface of the aluminum alloy plate by Nd:YAG laser processing, the conductive polymer was evenly coated on the template. Pressure sensors were packaged with a stencil transfer printing combined with an Ecoflex flexible substrate. Finally, the effects of different laser flux and the proportion of LIG in the composite on the sensitivity of the sensor are discussed. The results show that when the laser flux is 71.66 J·cm-2 and the mass fraction of LIG is 5%, the sensor has the best response characteristics, with a response time and a recovery time of 86 ms and 101 ms, respectively, with a sensitivity of 1.2 kPa-1 over a pressure range of 0-6 kPa, and stability of 650 cycle tests. The LIG/CCP sensor with a bionic structure demonstrates its potential in wearable devices.

Morphological and phylogenetic analyses reveal five new species of Porotheleaceae (Agaricales, Basidiomycota) from China.

The first occurrence of Marasmiellomycena and Pulverulina in the Chinese mycobiota are reported, M.tomentosa and P.flavoalba, two new species and M.albodescendens, a new combination, revealed by phylogenetic analyses and morphological study. These newly-recorded genera, Marasmiellomycena, which can be distinguished by their agaricoid basidiomata, dark-coloured stipe, sarcodimitic tramal structure, stipitipellis with yellow to yellowish-brown pigments and yellow-pigmented thick-walled caulocystidia and Pulverulina, which differs from other genera of Porotheleaceae by its pruinose stipe, decurrent lamellae, inamyloid basidiospores and absence of hymenial cystidia. We also formally describe three other new species of Porotheleaceae collected from Chinese temperate to subtropical zones of Fujian and Zhejiang Provinces: Clitocybulafuscostriata, Gerronemabrunneosquamulosum and Leucoinocybesubglobispora. Furthermore, we include the results of a phylogenetic analysis of Porotheleaceae, based on a multi-locus (ITS, nrLSU and rpb2) dataset. According to this analysis, Chrysomycena, Clitocybula, Delicatula, Hydropodia, Hydropus, Leucoinocybe, Marasmiellomycena, Megacollybia, Pulverulina, Trogia and Vizzinia are monophyletic. However, Gerronema is identified as polyphyletic and, additionally, Porotheleum does not form a monophyletic group either because Porotheleumparvulum and Porotheleumalbidum are "unassigned" in phylogenetic analysis. The results of our phylogenetic analyses, coupled with morphological observations, confirm recognition of these new taxa. Morphological descriptions, photographs, line drawings and comparisons with closely-related taxa are presented for the new species. A key to the 22 species belonging to nine genera of Porotheleaceae in China is also provided.

Transcriptome Analysis Explored the Differential Genes' Expression During the Development of the Stropharia rugosoannulata Fruiting Body.

Stropharia rugosoannulata (S. rugosoannulata) is a fungus with great edible and nutritional values; however, the development mechanism of its fruiting body has not been studied. Thus, this study aimed to analyze the differentially expressed genes (DEGs) in four stages; primordia stage (Sra1), young mushroom stage (Sra2), picking stage (Sra3), and opening umbrella stage (Sra4). Therefore, total RNA was extracted for further RNA-sequencing analysis. In three pairwise comparison groups (PCGs), Sra1 vs. Sra2, Sra2 vs. Sra3, and Sra3 vs. Sra4, a total of 3,112 DEGs were identified among the three PCGs. A GO analysis of the DEGs showed that there were 21 terms significantly enriched in Sra1 vs. Sra2 PCG. There was no significantly enriched GO term in the other two PCGs. Furthermore, KEGG pathway analysis showed that these DEGs were mainly enriched in glucose and amino acid metabolisms. Moreover we found that intron retention (IR) and the alternative 3' splice site (A3SS) accounted for more than 80%. The development of the S. rugosoannulata fruiting body mainly involved glucose and amino acid metabolisms. IR and A3SS were the two main types of ASE, which played an important role in the development and maturation of the S. rugosoannulata fruiting body.

Astragaloside IV alleviates senescence of vascular smooth muscle cells through activating Parkin-mediated mitophagy.

Astragaloside IV (AS-IV), as one of the main active components of Astragalus membranaceus, has been reported to have cardiovascular protective effects. However, the role and molecular mechanism of AS-IV in vascular senescence have not been clearly stated. The in vitro aging model was constructed using bleomycin (BLM) in vascular smooth muscle cells (VSMCs). Cell senescence were assessed through Western blotting analysis of aging markers, flow cytometry, and the ß-galactosidase (SA-ß-Gal) kit. Mitophagy was determined through transmission electron microscopy, TMRM staining, and Western blotting analysis of p62. A model of aging blood vessels was induced by D-gal. The vascular wall thickness of mice was also evaluated by H&E staining. Our data proved that AS-IV plays an anti-senescent role in vitro and in vivo. Results showed that AS-IV effectively improved mitochondrial injury, raised MMP, and mediated mitophagy in BLM-induced senescent VSMCs and D-gal induced aging mice. Parkin expression strengthened AS-IV's anti-senescent function. In conclusions, AS-IV attenuated BLM-induced VSMC senescence via Parkin to regulate mitophagy. Therefore, AS-IV-mediated Parkin might be a latent therapeutic agent and target for VSMC senescence.

A multifunctional nanoplatform for improving microwave hyperthermia by a combination therapy of vessel disruptive agent and immune modulator.

Microwave (MW) hyperthermia is one of the safest and most efficient minimally invasive tumor treatment methods, it is restricted by the bottlenecks of the heat sink effect and ineffective immune activation. Herein, a multifunctional nano platform with the load of nano immune modulator bimetallic metal-organic framework (BM), tumor vessel destructive agent and prodrug for gas production is developed for improving MW hyperthermia. Specifically, the combretastatin A4 phosphate (CA4P) was a vessel destructive agent to reduce MW heat loss by destructing the tumor blood vessel. Moreover, the as designed BM can scavenge the endogenic reactive oxygen species, which is conducive to hydrogen sulfide gas (H2S) that produced by bismuth sulfide (Bi2S3) to activate immune cells. Our in vivo experimental results demonstrate the destruction of tumor blood vessels coupled with the activated immune system results in the remarkable antitumor effect. This study provides an efficient strategy to improve MW hyperthermia by a combination of vasculature-targeting therapy with systemic immunity.

Metabolomics and transcriptomics unravel the mechanism of browning resistance in Agaricus bisporus.

Agaricus bisporus is widely consumed on the world market. The easy browning of mushroom surface is one of the most intuitive factors affecting consumer purchase. A certain cognition on browning mechanism has been made after years of research. At present, people slow down the browning of mushrooms mainly by improving preservation methods. In addition, breeding is also a reliable way. In the production practice, we have identified some browning-resistant varieties, and we selected a browning-resistant variety to compare with an ordinary variety to reveal the resistance mechanism. Using transcriptomics and metabolomics, the differences in gene expression and metabolite levels were revealed, respectively. The results showed that differentially expressed genes (DEGs) like AbPPO4, AbPPO3 and AbPPO2 were differently expressed and these DEGs were involved in many pathways related to browning. The expression of AbPPO expression play an important role in the browning of A. bisporus and multiple PPO family members are involved in the regulation of browning. However, the resistance to browning cannot be judged only by the expression level of AbPPOs. For metabolomics, most of the different metabolites were organic acids. These organic acids had a higher level in anti-browning (BT) than easy-browning varieties (BS), although the profile was very heterogeneous. On the contrary, the content of trehalose in BS was significantly higher than that in BT. Higher organic acids decreased pH and further inhibited PPO activity. In addition, the BS had a higher content of trehalose, which might play roles in maintaining PPO activity. The difference of browning resistance between BS and BT is mainly due to the differential regulation mechanism of PPO.

Disparities in alcohol use and heavy episodic drinking among bisexual people: A systematic review, meta-analysis, and meta-regression.

BACKGROUND: Alcohol consumption is more prevalent among sexual minorities than among heterosexuals; however, differences between minority sexual orientation groups are understudied. This systematic review and meta-analysis aimed to summarize existing evidence on the prevalence of alcohol use among bisexual people compared to their lesbian/gay and heterosexual counterparts. METHODS: A systematic review of literature from 1995 to May 2020 was performed using Medline, PsycInfo, and Embase (OVID), Scopus, CINHAL and LGBT Life (EBSCO), combining keywords for bisexuality and alcohol use. Peer-reviewed publications that reported quantitative data on alcohol use among bisexual people were included. A random-effects model was used to pool the prevalence of two outcomes: any alcohol use and heavy episodic drinking (HED). Subgroup analysis and random-effects meta-regression were used to explore heterogeneity. RESULTS: Of 105 studies eligible for data extraction, the overall prevalence of alcohol use was higher among bisexuals compared to lesbian/gay and heterosexual people. For example, the prevalence of past-month HED was 30.0% (28.2, 31.8) among bisexual people versus 25.5% (23.8, 27.2) among lesbian/gay and 21.3% (19.6, 23.0) among heterosexual individuals. Pooled odds ratio estimates showed that bisexual people were more likely to report alcohol use and HED compared to their counterparts. Gender was a significant effect modifier in meta-regression analysis, with greater disparities among women than among men. CONCLUSIONS: These results highlight the need for additional research to understand factors underlying bisexual people's greater risk, and particularly bisexual women, as well as alcohol use interventions that are targeted towards the specific needs of bisexual people.

Performance of Exergetic, Energetic and Techno-Economic Analyses on a Gas-Type Industrial Drying System of Black Tea.

The purpose of this research work is to perform detailed exergetic, energetic and techno-economic analysis of the black tea drying process in the gas-type industrial dryer. Exergy-energy and techno-economic methodology was applied to investigate the heat loss, exergetic and energetic performance, exergy efficiency, improvement potential rate, sustainability index and techno-economic performance of a drying system. The results showed that the heat loss of exhaust air in the late drying process played a main contributing role in the heat loss and exergy loss of the whole drying system. Therefore, the exergy efficiency of the initial drying period and the redrying period varied from 38.08% to 65.09% and 24.76% to 26.97%, respectively. In addition, the improvement potential rate and sustainability index of the whole system varied from 6.93 kW to 12.94 kW and 1.33 to 2.86, respectively. The improvement potential obtained in the present work indicated that the drying operation is greatly in need of exergy performance improvement. Finally, the net present value and payback period obtained from techno-economic analysis were 179,442.03 USD and 5.3 years, the result is useful for investors or contractors to refer to and make investment decisions.

Taxonomy and multi-gene phylogeny of Micropsalliota (Agaricales, Agaricaceae) with description of six new species from China.

Micropsalliota is a relatively small genus containing only 62 previously identified species. Here, we describe six new taxa of Micropsalliota based on morphological and phylogenetic analyses: M. minor, M. ovalispora, M. pseudodelicatula, M. rufosquarrosa, M. tenuipes, and M. wuyishanensis and a new record taxon to China. The first Maximum likelihood and Bayesian analyses of a three-gene dataset (ITS, LSU, and rpb2) separated the genus into 18 weakly to strongly supported major clades and subclades, but only a few subclades were synapomorphies. According to phylogenetic analyses, M. cornuta does not belong in Micropsalliota. A key to 20 species of Micropsalliota in China is provided.

Tropisetron inhibits sepsis by repressing hyper-inflammation and regulating the cardiac action potential in rat models.

OBJECTIVE: The objective of the present investigation was to explore the possible effect of the 5-HT3 receptor antagonist tropisetron on the expression levels of the inflammatory factors interleukin 6 (IL-6), creatine kinase isoenzyme (CK-MB), soluble growth stimulating gene 2 protein (sST2) and immunoglobulin E (IgE), as well as the cardiac action potential in septic rats. METHODS: The cecal ligation and perforation (CLP) method was utilized to construct abdominal infarction in rats. A total of 68 male adult Sprague Dawley rats were used, including 40 for assessing survival and 28 for detecting the expression levels of IL-6 and IgE, myocardial injury, cardiac dysfunction and the cardiac action potential. These 28 rats were divided into the sham (6 rats), sham + Tropisetron (6 rats), CLP (8 rats) and CLP + Tropisetron (8 rats) groups. Twenty-four hours after establishment of the sepsis rat model, immunohistochemistry was used to analyze 5-HT3 receptor protein expression, and enzyme-linked immunosorbent assay (ELISA) was employed to monitor the serum levels of IL-6, CKMB, sST2 and IgE. Furthermore, the structure of the myocardium in various groups was examined by H&E staining. RESULTS: The levels of IL-6, CK-MB, sST2 and IgE in the sepsis group were significantly higher than those of the sham group (P < 0.01). Furthermore, the heart rate in the sepsis group was lower than that of the sham group (P < 0.01), and the time of atrial ventricular action potential in the sepsis group was longer than that of the sham group (P < 0.05). In addition, immunohistochemical analyses showed that the area, intensity and index of 5-HT3 receptor in the sepsis group were significantly lower than those of the sham group (P < 0.01). Importantly, the 5-HT3 receptor antagonist Tropisetron exhibited significant inhibitory effects IL-6, CK-MB, sST2 and IgE expression levels, and inductive effects on atrial ventricular action potential in the sepsis group. CONCLUSIONS: Sepsis leads to systemic inflammatory reaction, resulting in myocardial injury, structural changes and immune imbalance. The inhibitory effect of tropisetron on inflammation, and the regulatory inflammatory disorder by the efferent vagus nerve may be one of the important mechanisms leading to cardiac electrophysiological changes in sepsis.

[Cox regression analysis on influencing factors of coronary heart disease among people over 40 years of age].

OBJECTIVE: To explore the affecting factors on coronary heart disease among people over 40 years of age in Guangxi area, China. METHODS: Baseline data was gathered through the Third National Blood Pressure Survey in 1991 in China. A total number of 11 818 adults over 40 years old had been studied in Guangxi province. Data of morbidity and mortality of coronary heart disease was obtained. RESULTS: Cardiovascular events were related to systolic blood pressure, diastolic blood pressure, pulse pressure, smoking, BMI regardless of their myocardial infarct (MI) history. Cox regression analysis showed that the relative risk for cardiovascular events increased by 21 [95% confidence interval (CI): 9.06-48.44] times for those people having MI history. When pulse pressure, systolic blood pressure, diastolic blood pressure increased by every 10 mm Hg, the relative risk for cardiovascular events increased by 1.29 (95% CI: 1.11-1.49), 1.18 (95% CI: 1.02-1.22), 1.13 (95% CI: 1.05-1.28) respectively. There was 1.23 (95% Cl: 1.05-1.45) times higher in smoker than non-smoker on relative risk for cardiovascular events. When BMI increasing 1, the relative risk for cardiovascular events would increase 1.03 (95% CI: 1.01-1 .05) times. CONCLUSION: Hypertension, smoking, increase of BMI were the risk factors of coronary heart disease among people who were over 40 years of age.