Three-dimensional cultured human umbilical cord mesenchymal stem cells attenuate pulmonary fibrosis by improving the balance of mitochondrial fusion and fission.

Pulmonary fibrosis is a kind of fibrotic interstitial pneumonia with poor prognosis. Aging, environmental pollution, and coronavirus disease 2019 are considered as independent risk factors for pulmonary fibrogenesis. Consequently, the morbidity and mortality striking continues to rise in recent years. However, the clinical therapeutic efficacy is very limited and unsatisfactory. So it is necessary to develop a new effective therapeutic approach for pulmonary fibrosis. Human umbilical cord mesenchymal stem cells (hucMSCs) are considered as a promising treatment for various diseases because of their multiple differentiation and immunomodulatory function. The key bottleneck in the clinical application of hucMSCs therapy is the high-quality and large-scale production. This study used FloTrix miniSpin bioreactor, a three-dimensional (3D) cell culture system, for large-scale expansion of hucMSCs in vitro, and proved 3D cultured hucMSCs inhibited the differentiation of fibroblasts into myofibroblasts and myofibroblasts proliferation and migration, leading to slow down the development of pulmonary fibrosis. Further mechanistic studies clarified that hucMSCs reduced the amount of binding between circELP2 and miR-630, resulting in blocking YAP/TAZ translocation from cytoplasm to nucleus. This condition inhibited mitochondrial fusion and promoted mitochondrial fission, and ultimately improved fusion/fission balance and cellular homeostasis. To sum up, this work clarified the anti-fibrosis and mechanism of hucMSCs cultured from the 3D FloTrix miniSpin bioreactor. We hope to provide new ideas and new methods for the clinical transformation and industrialization of hucMSCs therapy.

Picocyanobacterial-bacterial interactions sustain cyanobacterial blooms in nutrient-limited aquatic environments.

Cyanobacterial blooms (CBs) and concomitant water quality issues in oligotrophic/mesotrophic waters have been recently reported, challenging the conventional understanding that CBs are primarily caused by eutrophication. To elucidate the underlying mechanism of CBs in nutrition-deficient waters, the changes in Chlorophyll a (Chl-a), cyanobacterial-bacterial community composition, and certain microbial function in Qingcaosha Reservoir, the global largest tidal estuary storage reservoir, were analyzed systematically and comprehensively after its pilot run (2011-2019) in this study. Although the water quality was improved and stabilized, more frequent occurrences of bloom level of Chl-a (>20 µg L-1) in warm seasons were observed during recent years. The meteorological changes (CO2, sunshine duration, radiation, precipitation, evaporation, and relative humidity), water quality variations (pH, total organic carbon content, dissolved oxygen, and turbidity), accumulated sediments as an endogenous source, as well as unique estuarine conditions collectively facilitated picocyanobacterial-bacterial coexistence and community functional changes in this reservoir. A stable and tight co-occurrence pattern was established between dominant cyanobacteria (Synechococcus, Cyanobium, Planktothrix, Chroococcidiopsis, and Prochlorothrix) and certain heterotrophic bacteria (Proteobacteria, Actinobacteria, and Bacteroidetes), which contributed to the remineralization of organic matter for cyanobacteria utilization. The relative abundance of chemoorganoheterotrophs and bacteria related to nitrogen transformation (Paracoccus, Rhodoplanes, Nitrosomonas, and Zoogloea) increased, promoting the emergence of CBs in nutrient-limited conditions through enhanced nutrient recycling. In environments with limited nutrients, the interaction between photosynthetic autotrophic microorganisms and heterotrophic bacteria appears to be non-competitive. Instead, they adopt complementary roles within their ecological niche over long-term succession, mutually benefiting from this association. This long-term study confirmed that enhanced nutrient cycling, facilitated by cyanobacterial-bacterial symbiosis following long-term succession, could promote CBs in oligotrophic aquatic environments devoid of external nutrient inputs. This study advances understanding of the mechanisms that trigger and sustain CBs under nutritional constraints, contributing to developing more effective mitigation strategies, ensuring water safety, and maintaining ecological balance.

Study on the Effect of Two-Stage Injection Strategy for Coal-to-Liquid/Gasoline Reactivity-Controlled Compression Ignition Combustion Mode.

An experimental study was carried out on a modified single-cylinder dual-fuel engine in reactivity-controlled compression ignition (RCCI) mode using pilot fuels with different physicochemical properties, and the effects of the pilot fuels and the two-stage injection strategy on the combustion and emission characteristics of the RCCI mode were explored. The results show that when coal-to-liquid (CTL) is used with a high cetane number as the pilot fuel, the reactivity stratification of the fuel-air mixture is more pronounced. With the advancement of pilot injection timing (SOI1), the heat release rate (HRR) of the CTL/gasoline mode gradually changes from a bimodal pattern to a unimodal pattern. Among them, the bimodal HRR includes CTL premixed combustion and gasoline flame propagation, as well as CTL diffused combustion and gasoline multipoint spontaneous combustion, while the unimodal HRR represents CTL premixed combustion and gasoline multipoint spontaneous combustion. However, the HRR of the fossil diesel/gasoline RCCI combustion mode always exhibits a unimodal form. With the advancement of the main injection timing (SOI2), the gravity center of heat release (CA50) is more advanced when using CTL as the pilot fuel due to the short ignition delay. Overall, compared to fossil diesel, using CTL as the pilot fuel is conducive to controlling the pressure rise rate, which expands the operating range of the RCCI combustion mode. Besides, for both pilot fuels of CTL and fossil diesel, the advancement of SOI1 lowers particle emissions, and the advancement of SOI2 reduces NOx emissions, while the two-stage injection achieves higher indicated thermal efficiency.

The Gene vepN Regulated by Global Regulatory Factor veA That Affects Aflatoxin Production, Morphological Development and Pathogenicity in Aspergillus flavus.

Velvet (VeA), a light-regulated protein that shuttles between the cytoplasm and the nucleus, serves as a key global regulator of secondary metabolism in various Aspergillus species and plays a pivotal role in controlling multiple developmental processes. The gene vepN was chosen for further investigation through CHIP-seq analysis due to significant alterations in its interaction with VeA under varying conditions. This gene (AFLA_006970) contains a Septin-type guanine nucleotide-binding (G) domain, which has not been previously reported in Aspergillus flavus (A. flavus). The functional role of vepN in A. flavus was elucidated through the creation of a gene knockout mutant and a gene overexpression strain using a well-established dual-crossover recombinational technique. A comparison between the wild type (WT) and the ΔvepN mutant revealed distinct differences in morphology, reproductive capacity, colonization efficiency, and aflatoxin production. The mutant displayed reduced growth rate; dispersion of conidial heads; impaired cell wall integrity; and decreased sclerotia formation, colonization capacity, and aflatoxin levels. Notably, ΔvepN exhibited complete growth inhibition under specific stress conditions, highlighting the essential role of vepN in A. flavus. This study provides evidence that vepN positively influences aflatoxin production, morphological development, and pathogenicity in A. flavus.

Protective effects of sodium butyrate on fluorosis in rats by regulating bone homeostasis and serum metabolism.

Fluorosis due to high fluoride levels in drinking water profoundly affects the development of human skeletal and dental structures. Sodium butyrate (NaB) has been found to regulate overall bone mass and prevent pathological bone loss. However, the mechanism of NaB action on fluorosis remains unclear. In this study, a rat model of fluorosis induced by 100 mg/L sodium fluoride was used to investigate the impact of NaB on bone homeostasis and serum metabolomics. It was found that NaB significantly reduced the levels of bone resorption markers CTX-Ⅰ and TRACP-5B in fluorosis rats. Moreover, NaB increased calcium and magnesium levels in bone, while decreasing phosphorus levels. In addition, NaB improved various bone microstructure parameters, including bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone separation (Tb. SP), and structural model index (SMI) in the femur. Notably, NaB intervention also enhanced the antioxidant capacity of plasma in fluorosis rats. Furthermore, a comprehensive analysis of serum metabolomics by LC-MS revealed a significant reversal trend of seven biomarkers after the intervention of NaB. Finally, pathway enrichment analysis based on differential metabolites indicated that NaB exerted protective effects on fluorosis by modulating arginine and proline metabolic pathways. These findings suggest that NaB has a beneficial effect on fluorosis and can regulate bone homeostasis by ameliorating metabolic disorders.

Who benefit from adjuvant chemotherapy in stage I lung adenocarcinoma? A multi-dimensional model for candidate selection.

BACKGROUND: Despite promising overall survival of stage I lung adenocarcinoma (LUAD) patients, 10-25 % of them still went through recurrence after surgery. [1] While it is still disputable whether adjuvant chemotherapy is necessary for stage I patients. [2] IASLC grading system for non-mucinous LUAD shows that minor high-grade patterns are significant indicator of poor prognosis. [3] Other risk factors, such as, pleura invasion, lympho-vascular invasion, STAS, etc. are also related to poor prognosis. [4-6] There still lack evidence whether IASLC grade itself or together with other risk factors can guide the use of adjuvant therapy in stage I patients. In this article, we tried to establish a multi-variable recurrence prediction model for stage I LUAD patients that is able to identify candidates of adjuvant chemotherapy. METHODS: We retrospectively collected patients who underwent lung surgery from 2018.8.1 to 2018.12.31 at our institution and diagnosed with lung adenocarcinoma pT1-2aN0M0 (stage I). Clinical data, manifestation on CT scan, pathologic features, driver gene mutations and follow-up information were collected. Cox proportional hazards regression analyses were performed utilizing the non-adjuvant cohort to predict disease free survival (DFS) and a nomogram was constructed and applied to the total cohort. Kaplan-Meier method was used to compare DFS between groups. Statistical analysis was conducted by R version 3.6.3. FINDINGS: A total of 913 stage I LUAD patients were included in this study. Median follow-up time is 48.1 months.4-year and 5-year DFS are 92.9 % and 89.6 % for the total cohort. 65 patient experienced recurrence or death. 4-year DFS are 97.0 %,94.6 % and 76.2 %, and 5-year DFS are 95.5 %, 90.0 % and 74.1 % in IASLC Grade1, 2 and 3, respectively(p < 0.0001). High-risk patients defined by single risk factors, such as, IASLC grade 3, pleura invasion, STAS, less LN resected could not benefit from adjuvant therapy. A LASSO-COX regression model was built and patients are divided into high-risk and low-risk groups. In the high-risk group, patients underwent adjuvant chemotherapy have longer DFS than those who did not (p = 0.024), while in the low-risk group, patients underwent adjuvant chemotherapy have inferior DFS than those who did not (p < 0.001). INTERPRETATION: IASLC grading is a significant indicator of DFS, however it could not guide adjuvant therapy in our stage I LUAD cohort. Growth patterns and T indicators together with other risk factors could identify high-risk patients that are potential candidate of adjuvant therapy, including some stage IA LUAD patients.

circELP2 reverse-splicing biogenesis and function as a pro-fibrogenic factor by targeting mitochondrial quality control pathway.

Idiopathic pulmonary fibrosis (IPF) is considered as a chronic, fibrosing interstitial pneumonia with unknown mechanism. The present work aimed to explore the function, biogenesis and regulatory mechanism of circELP2 in pulmonary fibrosis and evaluate the value of blocking circELP2-medicated signal pathway for IPF treatment. The results showed that heterogeneous nuclear ribonucleoprotein L initiated reverse splicing of circELP2 resulting in the increase of circELP2 generation. The biogenetic circELP2 activated the abnormal proliferation and migration of fibroblast and extracellular matrix deposition to promote pulmonary fibrogenesis. Mechanistic studies demonstrated that cytoplasmic circELP2 sponged miR-630 to increase transcriptional co-activators Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ). Then, YAP1/TAZ bound to the promoter regions of their target genes, such as mTOR, Raptor and mLST8, which in turn activated or inhibited the genes expression in mitochondrial quality control pathway. Finally, the overexpressed circELP2 and miR-630 mimic were packaged into adenovirus vector for spraying into the mice lung to evaluate therapeutic effect of blocking circELP2-miR-630-YAP1/TAZ-mitochondrial quality control pathway in vivo. In conclusion, blocking circELP2-medicated pathway can alleviate pulmonary fibrosis, and circELP2 may be a potential target to treat lung fibrosis.

COX6A2 deficiency leads to cardiac remodeling in human pluripotent stem cell-derived cardiomyocytes.

BACKGROUND: Cardiac remodeling is the initiating factor for the development of heart failure, which can result from various cardiomyopathies. Cytochrome c oxidase subunit 6A2 (COX6A2) is one of the components of cytochrome c oxidase that drives oxidative phosphorylation. The pathogenesis of myocardial remodeling caused by COX6A2 deficiency in humans remains unclear because there are no suitable research models. In this study, we established a COX6A2-deficient human cardiac myocyte (CM) model that mimics the human COX6A2 homozygous mutation and determined the effects of COX6A2 dysfunction and its underlying mechanism. METHODS: A human COX6A2 homozygous knockout cardiomyocyte model was established by combining CRISPR/Cas9 gene editing technology and hiPSC-directed differentiation technology. Cell model phenotypic assays were done to characterize the pathological features of the resulting COX6A2-deficient cardiomyocytes. RESULTS: COX6A2 gene knockout did not affect the pluripotency and differentiation efficiency of hiPSCs. Myocardial cells with a COX6A2 gene knockout showed abnormal energy metabolism, increased oxidative stress levels, abnormal calcium transport activity, and decreased contractility. In addition, L-carnitine and trimetazidine significantly improved energy metabolism in the COX6A2-deficient human myocardial model. CONCLUSIONS: We have established a COX6A2-deficient human cardiomyocyte model that exhibits abnormal energy metabolism, elevated oxidative stress levels, abnormal calcium transport, and reduced contractility. This model represents an important tool to gain insight into the mechanism of action of energy metabolism disorders resulting in myocardial remodeling, elucidate the gene-phenotype relationship of COX6A2 deficiency, and facilitate drug screening.

Proteomic analysis reveals the aging-related pathways contribute to pulmonary fibrogenesis.

Aging usually causes lung-function decline and susceptibility to chronic lung diseases, such as pulmonary fibrosis. However, how aging affects the lung-fibrosis pathways and leads to the occurrence of pulmonary fibrosis is not completely understood. Here, mass spectrometry-based proteomics was used to chart the lung proteome of young and old mice. Micro computed tomography imaging, RNA immunoprecipitation, dual-fluorescence mRFP-GFP-LC3 adenovirus monitoring, transmission electron microscopy, and other experiments were performed to explore the screened differentially expressed proteins related to abnormal ferroptosis, autophagy, mitochondria, and mechanical force in vivo, in vitro, and in healthy people. Combined with our previous studies on pulmonary fibrosis, we further demonstrated that these biological processes and underlying molecular players were also involved in the aging process. Our work depicted a comprehensive cellular and molecular atlas of the aging lung and attempted to explain why aging is a risk factor for pulmonary fibrosis and the role that aging plays in the progression of pulmonary fibrosis. The abnormalities of aging triggered an increase in mechanical force and ferroptosis, autophagy blockade, and mitochondrial dysfunction, which often appear during pulmonary fibrogenesis. We hope that the elucidation of these anomalies will help to enhance our understanding of senescence-inducing pulmonary fibrosis, thereby guiding the use of anti-senescence as an entry point for early intervention in pulmonary fibrosis and age-related diseases.

Three-Directional Spacer-Knitted Piezoresistant Strain and Pressure Sensor for Electronic Integration and On-Body Applications.

The advancement of smart textiles has resulted in significant development in wearable textile sensors and offers novel interfaces to sense physical movements in daily life. Knitting, as a traditional textile fabrication method, is being used in promising ways to realize fully seamless fabrication and unobtrusive sensing in wearable textile applications. However, current flat-knitted sensors can sense strain only in the horizontal plane. This research presents a novel fully machine-knitted spacer piezoresistive sensor structure with a three-directional sensing ability that can detect both the pressure in the vertical direction and the strain in the warp/weft direction. Besides, it can sense the pressure under 1 kPa, which is critical in comfortable on-body interaction, one-piece integration, and wearable applications. Three sizes spacer-knitted sensors are evaluated in terms of their mechanical performance, stability cycles, and reaction to external factors such as sweat, laundering, etc. Then, the effect of material choice on sensor performance is evaluated and the rationale behind the use of different materials is summarized. Specifically, this research presents a detailed evaluation of the applications with both a single sensor and multiple sensor arrays for fine and gross motion sensing in several scenarios. The testing results demonstrate a fully machine-knitted piezoresistive sensor that can detect multidirectional motions (vertical, warp, and weft directions). In addition, this knitted sensor is scalable and can be facilely and seamlessly integrated into any garment piece. This universal knitted sensor structure could be made with a wide variety of materials for high sensitivity for multidirectional strain/pressure sensing, making it a high-compatibility sensor structure for wearable applications.

Co-exposure to multiple vitamins and the risk of all-cause mortality in patients with diabetes.

Objective: Although the effect of vitamins on the risk of mortality in diabetic patients has been reported, most studies focus on individual vitamins. However, humans are often exposed to multiple vitamins simultaneously in daily life. Therefore, it is worth exploring the effects of co-exposure to multiple vitamins on the risk of mortality in diabetic patients. Methods: This study included diabetic patients aged ≥20WD years who participated in NHANES from 2003 to 2006. An unsupervised K-means clustering method was used to cluster eight vitamins in serum into several patterns of co-exposure to multiple vitamins, and the Cox proportional hazards model was used to evaluate the impact of different patterns of co-exposure to multiple vitamins on the risk of all-cause mortality in diabetic patients. Results: Three patterns of co-exposure to multiple vitamins were generated based on K-means clustering, namely, low-level, moderate-level, and high-level. Among the 484 diabetic patients, with a median follow-up of 13.7 years, a total of 211 deaths occurred. After adjusting for covariates, the individual vitamins had varying effects on the risk of all-cause mortality in diabetic patients. Compared to the low-level group of co-exposure to multiple vitamins, the high-level group significantly reduced the risk of all-cause mortality in diabetic patients, with a HR of 0.42 (95% CI: 0.20, 0.87). Subgroup analysis demonstrated that high levels of co-exposure to multiple vitamins significantly reduced the risk of all-cause mortality in males, individuals aged ≥ 60 years, and non-Hispanic White people with diabetes compared to the low-level group, with HR of 0.42 (95% CI: 0.18, 0.98), 0.53 (95% CI: 0.26, 0.98), and 0.26 (95% CI: 0.12, 0.58) respectively. Conclusion: While individual vitamins had different effects on the risk of all-cause mortality in patients with diabetes, high-level co-exposure to multiple vitamins significantly reduced the risk of all-cause mortality in patients with diabetes, with differences observed among genders, ages, and race. This suggests that when developing vitamin intervention strategies for patients with diabetes, consideration should be given not only to the dosage of individual vitamins but also to the variations between different population groups.

Dityrosine Aggravates Hepatic Insulin Resistance in Obese Mice by Altering Gut Microbiota and the LPS/TLR4/NF-κB Inflammatory Pathway.

SCOPE: Dityrosine is the main product of protein oxidation, which has been proved to be a threat to human health. This study aims to investigate whether dityrosine exacerbates insulin resistance by inducing gut flora disturbance and associated inflammatory responses. METHODS AND RESULTS: Mice fed with normal diet or high-fat diet (HFD) received daily gavage of dityrosine (320 µg kg-1 BW) or saline for consecutive 13 weeks. The effects of dityrosine on gut microbiota are verified by in vitro fermentation using fecal microbiota from db/m mice and db/db mice. As a result, dityrosine causes the insulin resistance in mice fed normal diet, and aggravates the effects of HFD on insulin sensitivity. Dityrosine increases the levels of lipopolysaccharide (LPS), lipopolysaccharide-binding protein (LBP), toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) but decreases levels of interleukin-10 (IL-10) in the plasma of CON and HFD-fed mice. The changes of gut flora composition caused by dityrosine are significantly correlated with the changes of inflammatory biomarkers. CONCLUSION: The effects of dityrosine on insulin resistance may be attributed to the reshaping of the gut microbiota composition and promoting the activity of the LPS/TLR4/NF-κB inflammatory pathway in HFD-induced obese individuals.

Identification and Characterization of Novel ACE Inhibitory and Antioxidant Peptides from Sardina pilchardus Hydrolysate.

Sardina pilchardus is a valuable source of bioactive peptides with potential applications in functional foods. In this study, we investigated the angiotensin-converting enzyme (ACE) inhibitory activity of Sardina pilchardus protein hydrolysate (SPH) produced using dispase and alkaline protease. Our results showed that the low molecular mass fractions (<3 kDa) obtained through ultrafiltration exhibited more effective ACE inhibition, as indicated by screening with ACE inhibitory activity. We further identified the low molecular mass fractions (<3 kDa) using an LC-MS/MS rapid screening strategy. A total of 37 peptides with potential ACE inhibitory activity were identified based on high biological activity scores, non-toxicity, good solubility, and novelty. Molecular docking was used to screen for peptides with ACE inhibitory activity, resulting in the identification of 11 peptides with higher -CDOCKER ENERGY and -CDOCKER INTERACTION ENERGY scores than lisinopril. The sequences FIGR, FILR, FQRL, FRAL, KFL, and KLF were obtained by synthesizing and validating these 11 peptides in vitro, all of which had ACE inhibitory activity, as well as zinc-chelating capacity. All six peptides were found to bind to the three active pockets (S1, S2, and S1') of ACE during molecular docking, indicating that their inhibition patterns were competitive. Further analysis of the structural characteristics of these peptides indicated that all six peptides contain phenylalanine, which suggests that they may possess antioxidant activities. After experimental verification, it was found that all six of these peptides have antioxidant activities, and we also found that the SPH and ultrafiltration fractions of SPH had antioxidant activities. These findings suggest that Sardina pilchardus may be a potential source of natural antioxidants and ACE inhibitors for the development of functional foods, and using LC-MS/MS in combination with an online database and molecular docking represents a promising, effective, and accurate approach for the discovery of novel ACE inhibitory peptides.

Nucisporomicrobium flavum gen. nov., sp. nov., a new member of the family Micromonosporaceae isolated from saline-alkali soil.

A Gram-stain-positive, aerobic actinobacterium, designated strain NEAU-24T, was isolated from saline-alkali soil collected from Daqing City, Heilongjiang Province, PR China. Strain NEAU-24T was found to produce abundant substrate mycelia but no aerial hyphae. The substrate mycelia formed irregular pseudosporangia consisting of nuciform spores, and the surface of the spores was smooth. 16S rRNA gene sequence analysis showed that strain NEAU-24T clustered with Pseudosporangium ferrugineum 3-44-a(19)T, Couchioplanes caeruleus subsp. azureus DSM 44103T and C. caeruleus subsp. caeruleus DSM 43634T within the family Micromonosporaceae and was most closely related to P. ferrugineum 3-44-a(19)T (99.17 %). The strain contained meso-diaminopimelic acid as the cell-wall diamino acid and MK-9(H6) as the menaquinone. The whole cell sugar profile consisted of glucose, galactose, xylose and arabinose. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, phosphatidylinositol and an unidentified lipid. The major fatty acids were summarized as C16 : 0, C15 : 0, C17 : 0, iso-C16 : 0 and iso-C17 : 0. The low digital DNA-DNA hybridization and average nucleotide identity values could differentiate strain NEAU-24T from its related type strains. The phenotypic, genetic and chemotaxonomic data also indicated that strain NEAU-24T occupied a branch separated from those of known genera in the family Micromonosporaceae. In addition, genomic analysis confirmed that strain NEAU-24T had the potential to produce chitinase. Therefore, strain NEAU-24T represents a novel species of a new genus and species in the family Micromonosporaceae, for which the name Nucisporomicrobium flavum gen. nov., sp. nov. is proposed. The type strain of Nucisporomicrobium flavum is NEAU-24T (=CCTCC AA 2020016T=JCM 33973T).

Optimal Design of the Gating and Riser System for Complex Casting Using an Evolutionary Algorithm.

The gating and riser system design is essential for both quality and cost in large-scale casting and is expected to reach several objectives simultaneously. However, even with the help of commercial simulation software, the design of gating and riser systems is still the result of a long-term trial-and-error optimal process owing to the conflict between the objectives. Several evolutionary algorithms (EAs) have been reported to be helpful in the selection of the geometrical dimensions of gating and riser systems. In this study, a route with sequential use of a multi-objective EA and single-objective optimization algorithm was developed to help design gating and riser systems, respectively. This route was applied in an actual case and verified using commercial simulation software. The results showed a dramatic decrease in the time cost in design and acceptable casting quality. Thus, the proposed design method is time-saving.

The inhibitory effects of simulated light sources on the activity of algae cannot be ignored in photocatalytic inhibition.

Harmful algal blooms (HABs) destroy the balance of the aquatic ecosystem, causing huge economic losses and even further endangers human health. In addition to traditional methods of algae removal, photocatalytic inhibition of algae is drawing more and more interests with rich application scenarios and considerable potential. Simulated visible light sources are used to excite photocatalytic materials and optimize their performance. However, most of the light irradiation intensities used in the study exceeded 50 mW/cm2. And the effects of intense light irradiation conditions on algal growth have rarely been addressed in previous studies. So we focused on the effect of different intensity of light irradiation on the growth of algae. We explored the relationship between light irradiation intensity and algal inactivation rate, and investigated the changes in ROS levels in algal cells under different light irradiation and the resulting response of the antioxidant system. We have found that several major antioxidant enzyme activities, such as SOD and CAT, were significantly higher and lipid peroxidation products (MDA) were accumulating. Intense light irradiation had the most direct effect on the photosynthetic system of algal cells, with the photosynthetic rate and relative electron transfer rate decaying to almost 0 within 30 min, indicating that algal photosynthesis was inhibited in a fairly short period of time. We further observed the physiological and morphological changes of algal cells during this process using TEM and found that the progressive dissolution of the cell membrane system and the damage of organelles associated with photosynthesis play a major role in promoting cell death. We thus conclude that light irradiation has a significant effect on the physiological activity of algal cells and is a non-negligible factor in the study of photocatalytic removal of harmful algae. It will provide theoretical guidance for the future study of photocatalysis on algae inhibition.

The crucial influence of trophic status on the relative requirement of nitrogen to phosphorus for phytoplankton growth.

Clarifying the pattern of relative nitrogen (N)-to-phosphorus (P) requirements for phytoplankton growth is of great significance for eutrophication mitigation and aquatic system management. The relative N-to-P requirement for phytoplankton growth is considered an essential trait determining species dominance within ecosystems and explaining phytoplankton response to nutrient availability. These requirements vary with environmental trophic status, though this variation remains unclear. Here, we evaluated the relative N-to-P requirements under different absolute nutrient levels using previous and current experimental data on eight phytoplankton species (three studied by us and five extrapolated from previous studies). Results showed that relative N-to-P requirements for phytoplankton growth decreased as absolute nutrient levels increased. Thus, N may be crucial for enhancing phytoplankton growth under low nutrient conditions, whereas P may be the primary limiting factor of phytoplankton growth under sufficient nutrient conditions. This result applies to single species as well as species assemblages, which are independent of species shifts occurring along water N:P gradients. The response observed in our large trophic status gradient may help elucidate the relative importance of N and P reductions in mitigating the impact of eutrophication on ecosystems.

KCNQ1-deficient and KCNQ1-mutant human embryonic stem cell-derived cardiomyocytes for modeling QT prolongation.

BACKGROUND: The slowly activated delayed rectifier potassium current (IKs) mediated by the KCNQ1 gene is one of the main currents involved in repolarization. KCNQ1 mutation can result in long-QT syndrome type 1 (LQT1). IKs does not participate in repolarization in mice; thus, no good model is currently available for research on the mechanism of and drug screening for LQT1. In this study, we established a KCNQ1-deficient human cardiomyocyte (CM) model and performed a series of microelectrode array (MEA) detection experiments on KCNQ1-mutant CMs constructed in other studies to explore the pathogenic mechanism of KCNQ1 deletion and mutation and perform drug screening. METHOD: KCNQ1 was knocked out in human embryonic stem cell (hESC) H9 line using the CRISPR/cas9 system. KCNQ1-deficient and KCNQ1-mutant hESCs were differentiated into CMs through a chemically defined differentiation protocol. Subsequently, high-throughput MEA analysis and drug intervention were performed to determine the electrophysiological characteristics of KCNQ1-deficient and KCNQ1-mutant CMs. RESULTS: During high-throughput MEA analysis, the electric field potential and action potential durations in KCNQ1-deficient CMs were significantly longer than those in wild-type CMs. KCNQ1-deficient CMs also showed an irregular rhythm. Furthermore, KCNQ1-deficient and KCNQ1-mutant CMs showed different responses to different drug treatments, which reflected the differences in their pathogenic mechanisms. CONCLUSION: We established a human CM model with KCNQ1 deficiency showing a prolonged QT interval and an irregular heart rhythm. Further, we used various drugs to treat KCNQ1-deficient and KCNQ1-mutant CMs, and the three models showed different responses to these drugs. These models can be used as important tools for studying the different pathogenic mechanisms of KCNQ1 mutation and the relationship between the genotype and phenotype of KCNQ1, thereby facilitating drug development.

Nocardia albiluteola sp. nov., a novel lignin-degrading actinobacterium isolated from rhizosphere soil of pumpkin.

A novel lignin-degrading actinobacterium, designated NEAU-G5T, was isolated from pumpkin rhizosphere soil collected from field in Mudanjiang, Heilongjiang Province, northeast China, and characterized using polyphasic approach. The prior 16S rRNA gene sequence similarities and phylogenic analysis showed that strain NEAU-G5T exhibited close phylogenetic relatedness to Nocardia miyunensis NBRC 108239T (98.82 %), Nocardia nova NBRC 15556T (98.75 %), Nocardia jiangxiensis NBRC 101359T (98.68 %) and Nocardia macrotermitis RB20T (98.61 %). Morphological and chemotaxonomic characteristics indicated that strain NEAU-G5T could be assigned to the genus Nocardia. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, an unidentified phospholipid and an unidentified lipid. The predominant menaquinone was MK-8(H4, ω-cycl). The major fatty acids (>10 %) were identified as C16 : 0, C18 : 1 ω9c, 10-methyl C18 : 0 and C18 : 0. Mycolic acids were present. The genomic DNA G+C content of strain NEAU-G5T was 68 mol%. Moreover, based on digital DNA-DNA hybridization and average nucleotide identity values, strain NEAU-G5T could be differentiated from its reference strains. In addition, an azure B plate decolorization test and genomic analysis indicated that strain NEAU-G5T had the ability to degrade lignin. On the basis of polyphasic characteristics, strain NEAU-G5T represents a novel species of the genus Nocardia, with the name Nocardia albiluteola sp. nov. The type strain is NEAU-G5T (=CCTCC AA 2021018T=DSM 110547T).

Boosting Electrocatalytic Oxygen Evolution over Ce-Co9 S8 Core-Shell Nanoneedle Arrays by Electronic and Architectural Dual Engineering.

An dual electronic and architectural engineering strategy is a good way to rationally design earth-abundant and highly efficient electrocatalysts of the oxygen evolution reaction (OER) for sustainable hydrogen-based energy devices. Here, a Ce-doped Co9 S8 core-shell nanoneedle array (Ce-Co9 S8 @CC) supported on a carbon cloth has been designed and developed to accelerate the sluggish kinetics of the OER. Profiting from valance alternative Ce doping, a fine core-shell structure and vertically aligned nanoneedle arrayed architecture, Ce-Co9 S8 @CC integrates modulated electronic structure, highly exposed active sites, and multidimensional mass diffusion channels; together, these afford a favorable catalyzed OER. Ce-Co9 S8 @CC exhibits remarkable performance in the OER in an alkaline medium, where the overpotential requires only 242 mV to deliver a current density of 10 mA cm-2 for the OER; this is 70 mV superior to that of Ce-free Co9 S8 catalyst and other counterparts. Good stability and impressive selectivity (nearly 100 % Faradic efficiency) are also demonstrated. When integrated into a two-electrode OER//HER electrolyzer, the as-prepared Ce-Co9 S8 @CC displays a low operation potential of 1.54 V at 10 mA cm-2 and long-term stability, thus demonstrating great potential for economical water electrolysis.