Metagenomic Views of Microbial Communities in Sand Sediments Associated with Coral Reefs.

Reef sediments, the home for microbes with high abundances, provide an important source of carbonates and nutrients for the growth and maintenance of coral reefs. However, there is a lack of systematic research on the composition of microbial community in sediments of different geographic sites and their potential effect on nutrient recycling and health of the coral reef ecosystem. In combination of biogeochemical measurements with gene- and genome-centric metagenomics, we assessed microbial community compositions and functional diversity, as well as profiles of antibiotic resistance genes in surface sediments of 16 coral reef sites at different depths from the Xisha islands in the South China Sea. Reef sediment microbiomes are diverse and novel at lower taxonomic ranks, dominated by Proteobacteria and Planctomycetota. Most reef sediment bacteria potentially participate in biogeochemical cycling via oxidizing various organic and inorganic compounds as energy sources. High abundances of Proteobacteria (mostly Rhizobiales and Woeseiales) are metabolically flexible and contain rhodopsin genes. Various classes of antibiotic resistance genes, hosted by diverse bacterial lineages, were identified to confer resistance to multidrug, aminoglycoside, and other antibiotics. Overall, our findings expanded the understanding of reef sediment microbial ecology and provided insights for their link to the coral reef ecosystem health.

Mean platelet volume and the association with all-cause mortality and cardiovascular mortality among incident peritoneal dialysis patients.

BACKGROUND: While mean platelet volume (MPV) is linked to severity and all-cause mortality in patients with sepsis, its association with all-cause mortality and cardiovascular mortality in patients treated with peritoneal dialysis (PD) remains unknown. OBJECTIVES: The purpose of this study was to estimate the relationship between MPV and all-cause mortality and cardiovascular mortality among patients treated with PD. METHOD: We retrospectively collected 1322 patients treated with PD from November 1, 2005 to August 31, 2019. All-cause mortality and cardiovascular mortality was identified as the primary outcome. MPV was classified into three categories by means of X-tile software. The correlation between MPV and all-cause mortality was assessed by Cox model. Survival curves were performed by Kaplan-Meier method. RESULTS: The median follow-up period was 50 months (30-80 months), and a total of 360 deaths were recorded. With respect to all-cause mortality, patients in MVP ≥ 10.2 fL had considerably higher risk of all-cause mortality among three models (HR 0.68, 95%CI 0.56-0.84; HR 0.70, 95%CI 0.56-0.87; HR 0.73, 95%CI 0.59-0.91; respectively). Moreover, patients treated with PD, whose MVP ≥ 10.2 fL, also suffered from significantly higher risk of cardiovascular mortality in model 1, 2, and 3 (HR 0.63, 95%CI 0.46-0.85; HR 0.66, 95%CI 0.48-0.91; HR 0.69, 95%CI 0.50-0.95; respectively). CONCLUSIONS: This study indicates that MPV is independently correlated with both all-cause mortality and cardiovascular mortality in PD.

Hyper-Production of Pullulan by a Novel Fungus of Aureobasidium melanogenum ZH27 through Batch Fermentation.

Pullulan, which is a microbial exopolysaccharide, has found widespread applications in foods, biomedicines, and cosmetics. Despite its versatility, most wild-type strains tend to yield low levels of pullulan production, and their mutants present genetic instability, achieving a limited increase in pullulan production. Therefore, mining new wild strains with robust pullulan-producing abilities remains an urgent concern. In this study, we found a novel strain, namely, Aureobasidium melanogenum ZH27, that had a remarkable pullulan-producing capacity and optimized its cultivation conditions using the one-factor-at-a-time method. To elucidate the reasons that drove the hyper-production of pullulan, we scrutinized changes in cell morphology and gene expressions. The results reveal that strain ZH27 achieved 115.4 ± 1.82 g/L pullulan with a productivity of 0.87 g/L/h during batch fermentation within 132 h under the optimized condition (OC). This pullulan titer increased by 105% compared with the initial condition (IC). Intriguingly, under the OC, swollen cells featuring 1-2 large vacuoles predominated during a rapid pullulan accumulation, while these swollen cells with one large vacuole and several smaller ones were prevalent under the IC. Moreover, the expressions of genes associated with pullulan accumulation and by-product synthesis were almost all upregulated. These findings suggest that swollen cells and large vacuoles may play pivotal roles in the high level of pullulan production, and the accumulation of by-products also potentially contributes to pullulan synthesis. This study provides a novel and promising candidate for industrial pullulan production.

Source Indication and Geochemical Significance of Sedimentary Organic Matters from the Xisha Area, the South China Sea.

Although various geochemical and geophysical investigations have already indicated a great resource potential in the Xisha area of the South China Sea, the origin of organic matter and molecular evidence for tracing the migration of hydrocarbons from deep petroleum reservoirs are still lacking. In this study, systematic organic geochemical analyses, including bulk organic matter parameters and lipid biomarkers were performed for deep sediments from two cores. The C/N ratios and δ13C and δ15N values of organic matter in most of the samples, together with the maxima of short-chain n-alkanoic acids and mid-chain n-alkanols, high abundances of monounsaturated fatty acids C18:1ω9 and C22:1ω13, jointly indicate the dominance of marine organic matter. n-Alkanes in sediments from core GMGS4-XH-W06B are characterized by small unresolved complex mixture (UCMs) humps, high odd/even predominance (OEP) and carbon preference index (CPI) values, clearly exhibiting characteristics of modern sediments. However, the sediments for core GMGS4-XH-W03B are featured with big UCMs, associated with OEP and CPI values around 1.0, showing signatures of petroleum hydrocarbons from high maturity sources. Considering the geologic background, the biomarker signatures are solid evidence for indicating the existence of underlying petroleum reservoirs, and may provide the valuable information for assessing the hydrocarbon resources in the Xisha area.

Evaluation of ergosterol composition and esterification rate in fungi isolated from mangrove soil, long-term storage of broken spores, and two soils.

Ergosterol is an important fungal-specific biomarker, but its use for fungal biomass estimation is still varied. It is important to distinguish between free and esterified ergosterols, which are mainly located on the plasma membrane and the cytosolic lipid particles, respectively. The present study analyzes free and esterified ergosterol contents in: (1) the fifty-nine strains of culturable fungi isolated from mangrove soil, (2) the broken spores of the fungus Ganoderma lucidum stored in capsule for more than 12 years, and (3) the mangrove soil and nearby campus wood soil samples by high performance liquid chromatography (HPLC). The results show that the contents of free and esterified ergosterols varied greatly in fifty-nine strains of fungi after 5 days of growth, indicating the diversity of ergosterol composition in fungi. The average contents of free and total ergosterols from the fifty-nine strains of fungi are 4.4 ± 1.5 mg/g and 6.1 ± 1.9 mg/g dry mycelia, respectively, with an average ergosterol esterification rate of 27.4%. The present study suggests that the fungi might be divided into two classes, one is fungi with high esterification rates (e.g., more than 27%) such as Nectria spp. and Fusarium spp., and the other is fungi with low esterification rates (e.g., less than 27%) such as Penicillium spp. and Trichoderma spp. Moreover, the ergosterol esterification rate in the spores of G. lucidum is 91.4% with a very small amount of free ergosterol (0.015 mg/g), compared with 41.9% with a higher level of free ergosterol (0.499 mg/g) reported in our previous study in 2007, indicating that free ergosterol degrades more rapidly than esterified ergosterol. In addition, the ergosterol esterification rates in mangrove soil and nearby campus wood soil samples range from 0 to 39.0%, compared with 80% in an old soil organic matter reported in a previous study, indicating the potential relationship between aging degree of fungi or soil and esterification rate. The present study proposes that both free and esterified ergosterols should be analyzed for fungal biomass estimation. When the ergosterol esterification rates in soils are higher, free ergosterol might be a better marker for fungal biomass. It is speculated that the ergosterol esterification rate in soils might contain some important information, such as the age of old-growth forests over time scales of centuries to millennia, besides the senescence degree of fungal mycelia in soils. KEY POINTS: • Fungi might be divided into two classes depending on ergosterol esterification rates. • Ergosterol esterification rate of broken spores stored for long time raised evidently. • Both free and esterified ergosterols should be analyzed for fungal biomass estimate. • Free ergosterol is a better marker for fungal biomass with a high esterification rate.

Characterization of Humic Substances in the Soils of Ophiocordyceps sinensis Habitats in the Sejila Mountain, Tibet: Implication for the Food Source of Thitarodes Larvae.

Humic substances in soil are considered to be an alternative food to the tender plant roots for Thitarodes larvae in the habitats of Ophiocordyceps sinensis in the Qinghai-Tibetan Plateau. However, there is no report involving the evaluation of their potential as a food source from the composition and structure of habitat soils. In this work, the composition and structure of humic substances in habitat soils from the Sejila Mountain, Tibet were characterized by diverse techniques for evaluating the nutritional value and possibility of humus as the food source for Thitarodes larvae. Fourier transform infrared spectroscopy revealed that humic acid may possess superior ability to provide the molecular segments for biosynthesizing lipids more than other humic fractions. Combining with the analysis of solid-state 13C nuclear magnetic resonance spectrum, the fractions of hydrophobic fulvic acid and hydrophilic fulvic acid are further considered as a potential food source for Thitarodes larvae. Overall, humic substances in habitat soils are rich in the molecular segments for biosynthesizing lipids and other important nutrients, which may provide the energy and material sources for maintaining the survival of Thitarodes larvae in the absence of tender plant roots, particularly in the annual cold winter. Combining with the evidence of physico-chemical parameters of habitat soils and stable carbon isotopic composition of major tender plant roots in the Sejila Mountain, the composition and structure of humic substances in habitat soils may provide a novel idea for the eco-friendly and semi-wild cultivation of Thitarodes larvae with low cost.

Geochemical Significance of Biomarkers in the Methane Hydrate-Bearing Sediments from the Shenhu Area, the South China Sea.

Biomarkers from methane hydrate-bearing sediments can provide vital evidence for microbial activities associated with methanogenesis and their relation to the formation of methane hydrates. However, the former mainly focus on intact polar lipids from these microorganisms, and rarely investigate molecular hydrocarbons such as acyclic isoprenoids and hopanes so far. In this work, the composition of biomarkers in the methane hydrate-bearing sediments in cores SH2B and SH7B from the Shenhu area, the South China Sea (SCS) were identified by gas chromatography-mass spectrometry (GC-MS) and comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC×GC-TOFMS). The occurrence of unresolved complex mixtures (UCMs) and 25-norhopane indicate that the organic matters in methane hydrate-bearing sediments underwent a high degree of biodegradation. Although specific biomarkers for methanogens were not identified, the UCMs, 25-norhopane, pristane, phytane, and hopanes can still indicate the microbial activities associated with methanogenesis. These molecular signals suggest that diverse microorganisms, particularly methanogens, were quite vigorous in the methane hydrate-bearing sediments. Further, the biomarkers identified in this study can also be steadily detected from deep oil/gas reservoirs. Considering numerous adjacent oil/gas reservoir systems, fault systems, and mud diapers occurred in the SCS, it can be inferred that microbial activities and deep oil/gas reservoirs may have jointly contributed to the formation of methane hydrate deposits in the SCS.

Novel Arsenic Markers for Discriminating Wild and Cultivated Cordyceps.

Ophiocordyceps sinensis has been utilized in China and adjacent countries for thousands of years as a rare functional food to promote health and treat diverse chronic diseases. In recent years, adulterants are usually identified in the processed products of wild O. sinensis. However, the effective adulteration examination has to be additionally performed except their routine test, and accordingly is time- and money-consuming. Recently, arsenic determination has become a necessary test for confirming whether the concentrations of inorganic arsenic are over the O. sinensis limit. In this work, the contents of total arsenic and As species in cultivated O. sinensis, Cordyceps militaris, and other edible fungi were determined by ICP-MS and HPLC-ICP-MS. The results suggest that the As speciation exhibits a species-specific behavior, and accompanies the effect of the As background. The proportions of unknown organic As and contents of total As may be considered as sensitive markers for discriminating wild O. sinensis. This result provides a novel clue for discriminating wild and artificially cultivated mushrooms/their products, with emphasis on arsenic markers for authenticating wild O. sinensis.

Human mitochondrial pyrroline-5-carboxylate reductase 1 promotes invasiveness and impacts survival in breast cancers.

Human mitochondrial pyrroline-5-carboxylate reductase (PYCR) is a house-keeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate to proline. This enzymatic cycle plays pivotal roles in amino acid metabolism, intracellular redox potential and mitochondrial integrity. Here, we hypothesize that PYCR1 might be a novel prognostic biomarker and therapeutic target for breast cancer. In this study, breast cancer tissue samples were obtained from Zhejiang University (ZJU set). Immunohistochemistry analysis was performed to detect the protein level of PYCR1, and Kaplan-Meier and Cox proportional analyses were employed in this outcome study. The prognostic significance and performance of PYCR1 mRNA were validated on 13 worldwide independent microarray data sets, composed of 2500 assessable breast cancer cases. Our findings revealed that both PYCR1 mRNA and protein expression were significantly associated with tumor size, grade and invasive molecular subtypes of breast cancers. Independent and pooled analyses verified that higher PYCR1 mRNA levels were significantly associated with poor survival of breast cancer patients, regardless of estrogen receptor (ER) status. For in vitro studies, inhibition of PYCR1 by small-hairpin RNA significantly reduced the growth and invasion capabilities of the cells, while enhancing the cytotoxicity of doxorubicin in breast cancer cell lines MCF-7 (ER positive) and MDA-MB-231 (ER negative). Further population study also validated that chemotherapy significantly improved survival in early-stage breast cancer patients with low PYCR1 expression levels. Therefore, PYCR1 might serve as a prognostic biomaker for either ER-positive or ER-negative breast cancer subtypes and can also be a potential target for breast cancer therapy.

Molecular characterization and gene expression of cathepsin L in Nile tilapia (Oreochromis niloticus).

Cathepsin L (CatL) has been widely known for its involvement in the innate immunity. However, it still remains poorly understand how CatL modulates the immune system of teleosts. Moreover, the CatL of Nile tilapia (NtCatL) has not been cloned or characterized. In this study, the gene encoding NtCatL was cloned, and was characterized by bioinformatics analysis, heterologous expression and protease activity assay. The coding sequence of NtCatL is 1017 bp in length and encodes 338 amino acid residues with a predicted molecular weight of 38.487 kDa and a theoretical isoelectric point of 5.79. NtCatL possesses the features of a typical cathepsin L, including one signal peptide, one propeptide region, and one papain family cysteine protease domain containing four active site residues (Gln135, Cys141, His281, and Asn305). The prediction of protein-protein interaction shows that NtCatL may interact with some functional proteins for realizing an immune function. Real-time quantitative PCR revealed the widespread transcriptional expression of NtCatL in six tissues of healthy Nile tilapia, and the NtCatL mRNA is significantly up-regulated after Streptococcus agalactiae challenge. These results suggest that NtCatL is likely to be involved in the immune reaction of Nile tilapia. Recombinant proteins from the mature domain (residues 117-337) of NtCatL were obtained by heterologous expression using pET28a and Rosetta (DE3) competent cells. A protein product with the high purity was obtained by using TALON Superflow purification rather than adopting HisTrap HP columns. The protease activity of the recombinant protein was verified by using a substrate hydrolyzing assay. This work has cloned and characterized the CatL from Nile tilapia for the first time, and contributes to elucidating the immunological functions of CatL.

Stable Carbon Isotope Composition of the Lipids in Natural Ophiocordyceps sinensis from Major Habitats in China and Its Substitutes.

Ophiocordyceps sinensis is one rare medicinal fungus produced in the Qinghai-Tibetan Plateau. Its quality and price varies hugely with different habitat, and its numerous substitutes have sprung up in functional food markets. This paper aims to discriminate the geographic origin of wild O. sinensis and its substitutes via element analyzer-isotope ratio mass spectrometry and gas chromatography-isotope ratio mass spectrometry. The δ13C values of major fatty acids in the lipids of O. sinensis are characterized unanimously by the variation relation C18:0 < C18:2 ≈ C16:0 < C18:1, while their fluctuation intervals are notably different between those of neutral and polar lipids. The comparative analysis of the δ13C ratios of major fatty acids in lipids of O. sinensis suggests that the δ13C patterns may be sensitive potential indicators to discriminate its geographical origin. The δ13C values of individual major fatty acids of lipids from the cultivated stromata of Cordyceps militaris (SCM), the fermented mycelia of Hirsurella sinensis (FMH) and Paecilomyces epiali (FMP) range from -31.2‰ to -29.7‰, -16.9‰ to -14.3‰, and -26.5‰ to -23.9‰, respectively. Their δ13C pattern of individual major fatty acids may be used as a potential indicator to discriminate the products of natural O. sinensis and its substitutes.

Depth-related coupling relation between methane-oxidizing bacteria (MOBs) and sulfate-reducing bacteria (SRBs) in a marine sediment core from the Dongsha region, the South China Sea.

The vertical distributions of methane-oxidizing bacteria (MOBs) and sulfate-reducing bacteria (SRBs) in the marine sediment core of DH-CL14 from the Dongsha region, the South China Sea, were investigated. To enumerate MOBs and SRBs, their specific genes of pmoA and apsA were quantified by a culture-independent molecular biological technique, real-time polymerase chain reaction (RT-PCR). The result shows that the pmoA gene copies per gram of sediments reached the maximum of 1,118,679 at the depth of 140-160 cm. Overall considering the detection precision, sample amount, measurement cost, and sensitivity to the seepage of methane from the oil/gas reservoirs or gas hydrates, we suggest that the depth of 140-160 cm may be the optimal sampling position for the marine microbial exploration of oils, gases, and gas hydrates in the Dongsha region. The data of the pmoA and apsA gene copies exhibit an evident coupling relation between MOBs and SRBs as illustrated in their vertical distributions in this sediment core, which may well be interpreted by a high sulfate concentration inhibiting methane production and further leading to the reduction of MOBs. In comparison with the numbers of the pmoA and apsA copies at the same sediment depth, we find out that there were two methane-oxidizing mechanisms of aerobic and anaerobic oxidation in this sediment core, i.e., the aerobic oxidation with free oxygen dominantly occurred above the depth of 210-230 cm, while the anaerobic oxidation with the other electron acceptors such as sulfates and manganese-iron oxides happened below the depth of 210-230 cm.

An effective method for the detoxification of cyanide-rich wastewater by Bacillus sp. CN-22.

The biodetoxification of cyanide-rich wastewater has become increasingly popular because of its cost-effectiveness and environmental friendliness. Therefore, we have developed an effective method, optimised by response surface methodology, for detoxifying cyanide-rich wastewater using Bacillus sp. CN-22, which was newly isolated from a cyanide-contaminated electroplating sludge and could tolerate a CN⁻ concentration of 700 mg L⁻¹. The concentration of CN⁻ in the treated wastewater decreased from 200 to 6.62 mg L⁻¹ after cultivation with 2.38 % inocula for 72 h on the medium, consisting of 0.05 % KH2PO4, 0.15 % K2HPO4, 1.0 mM MgCl2, 1.0 mM FeCl3, 0.1 % NH4Cl, and 0.1 % glycerol. The CN⁻ degradability of 96.69 % is similar to the predicted value of 96.82 %. The optimal cultivation conditions were controlled as follows: initial pH, 10.3; temperature, 31 °C; and rotary speed, 193 rpm. The maintenance of higher pH in the overall treatment procedures may avoid the production of volatile HCN and the risk associated with cyanide detoxification. Additionally, the bacterial strain Bacillus sp. CN-22, with its potent cyanide-degrading activity at the initial CN⁻ concentration of 200 mg L⁻¹, may be employed to effectively treat cyanide-rich wastewater, especially electroplating effluent.

Broad-spectrum hydrocarbon-degrading microbes in the global ocean metagenomes.

Understanding the diversity and functions of hydrocarbon-degrading microorganisms in marine environments is crucial for both advancing knowledge of biogeochemical processes and improving bioremediation methods. In this study, we leveraged nearly 20,000 metagenome-assembled genomes (MAGs), recovered from a wide array of marine samples across the global oceans, to map the diversity of aerobic hydrocarbon-degrading microorganisms. A broad bacterial diversity was uncovered, with a notable preference for degrading aliphatic hydrocarbons over aromatic ones, primarily within Proteobacteria and Actinobacteriota. Three types of broad-spectrum hydrocarbon-degrading bacteria were identified for their ability to degrade various hydrocarbons and possession of multiple copies of hydrocarbon biodegradation genes. These bacteria demonstrate extensive metabolic versatility, aiding their survival and adaptability in diverse environmental conditions. Evidence of gene duplication and horizontal gene transfer in these microbes suggested a potential enhancement in the diversity of hydrocarbon-degrading bacteria. Positive correlations were observed between the abundances of hydrocarbon-degrading genes and environmental parameters such as temperature (-5 to 35 °C) and salinity (20 to 42 PSU). Overall, our findings offer valuable insights into marine hydrocarbon-degrading microorganisms and suggest considerations for selecting microbial strains for oil pollution remediation.

Abundant small microplastics hidden in water columns of the Yellow Sea and East China Sea: Distribution, transportation and potential risk.

Microplastics (MPs) pose significant concerns for marine ecological security due to their minuteness and ubiquity. However, comprehensive knowledge on their distribution and fate in seawater columns remains limited. This study investigated the abundances and characteristics of MPs across 3-6 water layers in the South Yellow Sea and East China Sea. Results indicate that high-abundance small MPs (< 100 µm) (average 6567 items/m3) were hidden beneath the sea-surface, predominantly fine-grained particles (< 20 µm) and high-density polymers (> 1.03 g/cm3). The total suspended MPs (5.0-834.2 µm) are estimated at 2.9-3.1 × 1017 particles, with most of them occurring in upper layers. In profiles, their distribution varied by physical properties with depth; fragment-shaped and high-density MPs increased in proportion at greater depths, contrasting with fibrous MPs. These MPs originated primarily from the Yangtze River and their winter transport was driven by the Yangtze River Dilution Water, East China Sea Coastal Current, and Yellow Sea Warm Current, resulting in their accumulation in coastal and estuarine regions. Consequently, the Yangtze River Estuary ecosystem faces substantial risks from MP pollution throughout the water column. This work unveils the prevalence of small MPs in coastal water columns and intricate interaction between their fate and hydrodynamic conditions.

Microplastics in remote coral reef environments of the Xisha Islands in the South China Sea: Source, accumulation and potential risk.

Microplastics (MPs) are of great concern to coral health, particularly enhanced biotoxicity of small microplastics (< 100 µm) (SMPs). However, their fate and harm to remote coral reef ecosystems remain poorly elucidated. This work systematically investigated the distributions and features of MPs and SMPs in sediments from 13 islands/reefs of the Xisha Islands, the South China Sea for comprehensively deciphering their accumulation, sources and risk to coral reef ecosystems. The results show that both MPs (average, 682 items/kg) and SMPs (average, 375 items/kg) exhibit heterogeneous distributions, with accumulation within atolls and dispersion across fringing islands, which controlled by human activities and hydrodynamic conditions. Cluster analysis for the first time reveals a pronounced difference in their compositions between the southern and northern Xisha Islands and resultant distinct sources, i.e., MPs in the north part were leaked mainly from local domestic sewage and fishing waste, while in the south part were probably derived from industrial effluents from adjacent countries. Our ecological risk assessment suggests that the ecosystem within the Yongle Atoll is exposed to a high-risk of MPs pollution. The novel results and proposed framework facilitate to effectively manage and control MPs and accordingly preserve a fragile biosphere in remote coral reefs.

A field study to evaluate the impact of different factors on the nutrient pollutant concentrations in green roof runoff.

The objectives of this study are to investigate the impact of different factors on the nutrient pollutant concentrations in green roof runoff and to provide reference data for the engineering design of dual substrate layer green roofs. The data were collected from eight different trays under three kinds of artificial rains. The results showed that except for total phosphorus, dual substrate layer green roofs behaved as a sink for most of the nutrient pollutants (significant at p < 0.05), and the first-flush effect did not occur during the 27 simulated rain events. The results also revealed that the concentration of these nutrient pollutants in the runoff strongly depended on the features of the nutrient substrates used in the green roof and the depth of the adsorption substrates. Compared with the influence of the substrates, the influence of the plant density and drainage systems was small.

Sweroside functionalized with Mesenchymal Stem cells derived exosomes attenuates sepsis-induced myocardial injury by modulating oxidative stress and apoptosis in rats.

Sepsis is a life-threatening problem by organ dysfunction influenced by negative inflammatory responses and stimulated oxidative stress, which most of sepsis patients about 40-60% are accompanied with myocardial injury. Recently, stem cells derived exosomes could effectively apply in the numerous diseases by combined with natural therapeutic agents. In the present investigation, Sweroside functionalized with exosomes to control inflammatory responses by sepsis and significantly proved the function of depreciated myocardial injury-induced by LPS. The sweroside could have effectively delivered to cardiomyocytes cells via exosome carriers. The induced-SMI rats exhibited severe myocardial injury and apoptosis by in vivo experiments and treatment of sweroside-functionalized exosomes (SWO/EX) reassured the phenotypes. Importantly, SWO/EX significantly downregulated the ROS generation in the SMI rat models. The SOD and GSH activity were also suppressed in SMI rat models, and treated models with SWO/EXO could have effective liberating activity in the Rats. Meanwhile, SWO/EXO treated LPS-induced cardiomyocytes displayed that significant reduction of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) levels and also increasing cell survival and prevented apoptosis. Thus, we demonstrate that MS-cells derived exosome with sweroside could have effectively impede sepsis-induced myocardial injury. SWO/EX formulations might be applied as a potent therapeutic agent for SMI therapy.

Impact of N221S missense mutation in human ribonucleotide reductase small subunit b on mitochondrial DNA depletion syndrome.

The impact of N221S mutation in hRRM2B gene, which encodes the small subunit of human ribonucleotide reductase (RNR), on RNR activity and the pathogenesis of mitochondrial DNA depletion syndrome (MDDS) was investigated. Our results demonstrate that N221 mutations significantly reduce RNR activity, suggesting its role in the development of MDDS. We proposed an allosteric regulation pathway involving a chain of three phenylalanine residues on the αE helix of RNR small subunit ß. This pathway connects the C-terminal loop of ß2, transfers the activation signal from the large catalytic subunit α to ß active site, and controls access of oxygen for radical generation. N221 is near this pathway and likely plays a role in regulating RNR activity. Mutagenesis studies on residues involved in the phenylalanine chain and the regulation pathway were conducted to confirm our proposed mechanism. We also performed molecular dynamic simulation and protein contact network analysis to support our findings. This study sheds new light on RNR small subunit regulation and provides insight on the pathogenesis of MDDS.

Intelligent Optimization Design of a Phononic Crystal Air-Coupled Ultrasound Transducer.

To further improve the operational performance of a phononic crystal air-coupled ultrasonic transducer while reducing the number of simulations, an intelligent optimization design strategy is proposed by combining finite element simulation analysis and artificial intelligence (AI) methods. In the proposed strategy, the structural design parameters of 1-3 piezoelectric composites and acoustic impedance gradient matching layer are sampled using the optimal Latin hypercube sampling (OLHS) method. Moreover, the COMSOL software is utilized to calculate the performance parameters of the transducer. Based on the simulation data, a radial basis function neural network (RBFNN) model is trained to establish the relationship between the design parameters and the performance parameters. The accuracy of the approximation model is verified through linear regression plots and statistical methods. Finally, the NSGA-II algorithm is used to determine the design parameters of the transducer. After optimization, the band gap widths of the piezoelectric composites and acoustic impedance gradient matching layer are increased by 16 kHz and 13.5 kHz, respectively. Additionally, the -6 dB bandwidth of the transducer is expanded by 11.5%. The simulation results and experimental results are consistent with the design objectives, which confirms the effectiveness of the design strategy. This work provides a feasible strategy for the design of high-performance air-coupled ultrasonic transducers, which is of great significance for the development of non-destructive testing technology.