Heterometallic Eu/Zn-MOF-based ratiometric sensing platform: Highly sensitive fluorescence / second-order scattering identification of tetracycline analogs and its molecular informatization applications.

The traditional preparation method of ratiometric probes faces challenges such as cumbersome preparation and low sensitivity. Thus, there is an urgent need to provide a simple method of preparing a highly sensitive ratiometric probe. Here, Eu3+-doped zinc-based organic framework (Eu/Zn-MOF) was prepared through hydrothermal method for the detection of tetracycline analogs (TCs). Under the same excitation conditions, the probe can simultaneously display valuable fluorescence and second-order scattering signals. The developed probe enabled specific identification and fast detection (1 min) of TCs, including tetracycline, oxytetracycline, doxycycline, and chlortetracycline. The linear detection ranges of tetracycline, oxytetracycline, doxycycline and chlortetracycline were respectively 100 nM - 200 µM, 100 nM - 200 µM, 98 nM - 195 µM, and 97 nM - 291 µM, and the corresponding detection limits were respectively 15.79 nM, 20.83 nM, 15.31 nM, and 28.30 nM. The developed sensor was successfully applied to detect TCs in real samples, and the recovery rate was from 92.54 % to 109.69 % and the relative standard deviation was from 0.04 % to 2.97 %. Moreover, the heterometallic Eu/Zn-MOF was designed as a ratiometric neuron for Boolean logic computing and information encryption based on the specific identification of TCs. As a proof of concept, molecular steganography was successfully employed to encode, store, and conceal information by transforming the specific identification patterns of Eu/Zn-MOF into binary strings. This study is anticipated to advance the application of metal-organic frameworks in logic detection and information security, and bridging the gap between molecular sensors and the realm of information.

Streptomyces-Fungus Co-Culture Enhances the Production of Borrelidin and Analogs: A Genomic and Metabolomic Approach.

The marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic profiles of co-cultures involving Streptomyces sp. 2-85 and Cladosporium sp. 3-22-derived from marine sponges. Combining Global Natural Products Social (GNPS) Molecular Networking analysis with natural product database mining, 35 potential antimicrobial metabolites annotated were detected, 19 of which were exclusive to the co-culture, with a significant increase in production. Notably, the Streptomyces-Fungus interaction led to the increased production of borrelidin and the discovery of several analogs via molecular networking. In this study, borrelidin was first applied to combat Saprolegnia parasitica, which caused saprolegniosis in aquaculture. We noted its superior inhibitory effects on mycelial growth with an EC50 of 0.004 mg/mL and on spore germination with an EC50 of 0.005 mg/mL compared to the commercial fungicide, preliminarily identifying threonyl-tRNA synthetase as its target. Further analysis of the associated gene clusters revealed an incomplete synthesis pathway with missing malonyl-CoA units for condensation within this strain, hinting at the presence of potential compensatory pathways. In conclusion, our findings shed light on the metabolic changes of marine Streptomyces and fungi in co-culture, propose the potential of borrelidin in the control of aquatic diseases, and present new prospects for antifungal applications.

Risk factors for the recurrence of left atrioventricular valvular regurgitation after surgical repair of partial and transitional atrioventricular septal defect.

Background: Left atrioventricular valvular regurgitation (LAVVR) recurrence after partial and transitional atrioventricular septal defect (AVSD) repair is the main risk factor associated with reoperation or mortality. The purpose of this study was to identify risk factors associated with the recurrence of LAVVR after surgical repair of transitional and partial AVSD at a single institution. Methods: A hundred and fifty-seven patients who underwent anatomical repair for partial and transitional AVSD from January 2013 to December 2021 were included in our institutional database. Demographic characteristics, operative information, comorbidities, complications, and outcomes were retrieved from electronic medical records. Echocardiographic evaluations included cardiac dimensions, the degree of LAVVR, and the anatomy of the atrioventricular valve. Results: After a median follow-up period of 5.8 years, 40 patients had recurrent moderate or even more severe LAVVR. Compared with patients without recurrent LAVVR, those experiencing LAVVR recurrence were more likely to have larger preoperative left atrial (LA) size and larger left ventricular (LV) size after standardization, larger left atrioventricular valve (LAVV) cleft width, higher proportions of preoperative moderate or even more severe LAVVR, and immediately postoperative mild to moderate or even more severe LAVVR. Univariate Cox regression analysis showed that age at first repair, height, LA size after standardization, LV size after standardization, the severity of preoperative LAVVR, immediately postoperative LAVVR, and the LAVV cleft width more than 1cm were risk factors for recurrent LAVVR (P<0.05 for all). Multivariable Cox regression analysis showed that mild to moderate or even more severe LAVVR postoperatively [hazard ratio (HR) 9.53, 95% confidence interval (CI): 3.78-24.01; P<0.001], the width of LAVV cleft more than 1 cm (HR: 3.90, 95% CI: 1.80-8.48; P<0.001) and age at first repair (HR: 0.45, 95% CI: 0.31-0.66; P<0.001) were independently associated with the recurrence of LAVVR. Conclusions: The width of LAVV cleft, mild to moderate or even more severe LAVVR immediately after surgery, and age at initial surgery are risk factors for recurrent LAVVR. The presence of recurrent LAVVR necessitates proactive surveillance to facilitate timely reintervention.

Exploring future ecosystem service changes and key contributing factors from a "past-future-action" perspective: A case study of the Yellow River Basin.

Understanding the impacts of climate change and human activities on ecosystem services (ESs) and taking actions to adapt to and mitigate their negative impacts are of great benefit to sustainable regional development. In this paper, we integrate the System Dynamics Model (SD), the Future Land Use Simulation (FLUS) model, the Integrated Valuation and Trade-offs of ESs (InVEST) model, and the Structural Equation Model (SEM). We select three scenarios, SSP1-1.9, SSP2-4.5, and SSP5-8.5, from the Coupled Model Intercomparison Project 6 (CMIP6) to forecast future changes under these scenarios in the Yellow River Basin (YRB) by 2030. We predict future changes in water yield (WY), carbon storage (CS), soil retention (SR), and habitat quality (HQ) in the YRB. The results show that: (1) Under the SSP1-1.9 scenario, ecological land types such as forests, grasslands, and water bodies are protected and restored to a certain extent; under the SSP2-4.5 scenario, the degree of land spatial development occupies an intermediate state among the three scenarios; and under the SSP5-8.5 scenario, there is an obvious increase in the artificialization of the watershed's land use. (2) Under scenario SSP1-1.9, there is a comprehensive approach to sustainable development that significantly improves all ESs in the watershed, while the SSP5-8.5 and SSP2-4.5 scenarios demonstrate an increase in trade-offs between WY, HQ, and CS, especially in the downstream area. (3) Anthropogenic factors having more significant impacts in the SSP5-8.5 scenario. In this paper, we not only summarize the differences in trade-offs among various ESs but also provide an in-depth analysis of the key factors affecting future ESs, providing new ideas and insights for the sustainable development of ES in the future. In summary, we propose a prioritized development pathway for the future, a reduction of trade-offs between ESs, and an improved capacity to respond to challenges.

Association between regulatory T cells and ischemic heart disease: a Mendelian randomization study.

Background: An imbalance of innate and acquired immune responses is significantly involved in the pathophysiology of coronary atherosclerosis and the occurrence of ischemic heart disease (IHD). Regulatory T cells (Tregs) play an essential regulatory role in atherosclerotic plaque formation and maintenance; therefore, dysfunction of Tregs triggers the formation of atherosclerotic plaques and accelerates their progression. However, due to the inherent limitations of observational research, clinical evidence is limited concerning the relationship between the variation in peripheral Tregs and the risk of IHD, and the cause-and-effect relationship between these factors is unclear. Mendelian randomization (MR) uses genetic variation as a proxy for exposure and can be used to inferentially determine the causal effect of exposure on outcomes. We thus used MR analysis to investigate whether there is a causal relationship between the biomarkers of Tregs and IHD. Methods: Selected genetic variants (P<5.00E-08) from the summary data of a genome-wide association study (GWAS) were used to conduct a two-sample bidirectional MR analysis. The analysis included 51 extensive Treg subtypes involving 3,757 individuals from the general population. Summary statistics of IHD were obtained from the IEU open GWAS project, which contains 30,952 cases and 187,845 controls. The populations in both GWAS studies were of European ancestry. Results: We identified a set of 197 single-nucleotide polymorphisms (SNPs) that served as instrumental variables (IVs) for evaluating 51 Treg subtypes. Thirteen significant variables were found to be potentially associated with IHD. After false-discovery rate (FDR) adjustment, we identified four Treg subtypes to be causally protective for IHD risk: CD28 on activated & secreting CD4 Tregs [odds ratio (OR) =0.89; 95% confidence interval (CI): 0.82-0.96; P=3.10E-03; adjusted P=0.04], CD28 on activated CD4 Tregs (OR =0.87; 95% CI: 0.80-0.95; P=3.10E-03; adjusted P=0.04), CD28 on CD4 Tregs (OR =0.87; 95% CI: 0.80-0.96; P=3.41E-03; adjusted P=0.04), and CD28 on resting CD4 Treg cell (OR =0.91; 95% CI: 0.85-0.97; P=3.48E-03; adjusted P=0.04). Reverse MR analysis found eight potential causal variables, but these associations were nonsignificant after FDR correction (all adjusted P values >0.05). Conclusions: This study identified the significance of elevated CD28 expression on CD4 Tregs as a novel molecular modifier that may influence IHD occurrence, suggesting that targeting CD28 expression on CD4 Tregs could offer a promising therapeutic approach for IHD.

High-Order Neural-Network-Based Multi-Model Nonlinear Adaptive Decoupling Control for Microclimate Environment of Plant Factory.

Plant factory is an important field of practice in smart agriculture which uses highly sophisticated equipment for precision regulation of the environment to ensure crop growth and development efficiently. Environmental factors, such as temperature and humidity, significantly impact crop production in a plant factory. Given the inherent complexities of dynamic models associated with plant factory environments, including strong coupling, strong nonlinearity and multi-disturbances, a nonlinear adaptive decoupling control approach utilizing a high-order neural network is proposed which consists of a linear decoupling controller, a nonlinear decoupling controller and a switching function. In this paper, the parameters of the controller depend on the generalized minimum variance control rate, and an adaptive algorithm is presented to deal with uncertainties in the system. In addition, a high-order neural network is utilized to estimate the unmolded nonlinear terms, consequently mitigating the impact of nonlinearity on the system. The simulation results show that the mean error and standard error of the traditional controller for temperature control are 0.3615 and 0.8425, respectively. In contrast, the proposed control strategy has made significant improvements in both indicators, with results of 0.1655 and 0.6665, respectively. For humidity control, the mean error and standard error of the traditional controller are 0.1475 and 0.441, respectively. In comparison, the proposed control strategy has greatly improved on both indicators, with results of 0.0221 and 0.1541, respectively. The above results indicate that even under complex conditions, the proposed control strategy is capable of enabling the system to quickly track set values and enhance control performance. Overall, precise temperature and humidity control in plant factories and smart agriculture can enhance production efficiency, product quality and resource utilization.

Butylphthalide improves brain damage induced by renal ischemia-reperfusion injury rats through Nrf2/HO-1 and NOD2/MAPK/NF-κB pathways.

Renal ischemia-reperfusion (I/R) injury leads to irreversible brain damage with serious consequences. Activation of oxidative stress and release of inflammatory mediators are considered potential pathological mechanisms. Butylphthalide (NBP) has anti-inflammatory and antioxidant effects on I/R injuries. However, it is unclear whether NBP can effectively mitigate renal I/R secondary to brain injury as well as its mechanism, which are the aims of this study. Both renal I/R injury rats and oxygen and glucose deprivation cell models were established and pre-intervened NBP. The Morris water maze assay was used to detect behavior. Hippocampal histopathology and function were examined after renal I/R. Apoptosis and tube-forming capacity of brain microvascular endothelial cells (BMVECs) were tested. Immunohistochemistry and Western blot were used to measure protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway and NOD-like receptor C2 (NOD2)/Mitogen-activated protein kinases (MAPK)/Nuclear factor kappa-B (NF-κB) pathway. NBP treatment attenuated renal I/R-induced brain tissue damage and learning and memory dysfunction. NBP treatment inhibited apoptosis and promoted blood-brain barrier restoration and microangiogenesis. Also, it decreased oxidative stress levels and pro-inflammatory factor expression in renal I/R rats. Furthermore, NBP enhanced BMVECs' viability and tube-forming capacity while inhibiting apoptosis and oxidative stress. Notably, the alleviating effects of NBP were attributed to Nrf2/HO-1 pathway activation and NOD2/MAPK/NF-κB inhibition. This study demonstrates that NBP maintains BBB function by activating the Nrf2/HO-1 pathway and inhibiting the NOD2/MAPK/NF-κB pathway to suppress inflammation and oxidative stress, thereby alleviating renal I/R-induced brain injury.

Global burden and trends of transport injuries from 1990 to 2019: an observational trend study.

BACKGROUND: Transport injuries (TIs) are a major cause of global disability-adjusted life-years (DALYs) and mortality. In this study, we aimed to assess the global burden and trends of TIs from 1990 to 2019. METHODS: We assessed the annual age-standardised incidence rate (ASIR) and age-standardised DALYs rate of TIs by sex, age, Social Development Index (SDI) and geographical region from 1990 to 2019 from the Global Burden of Disease Study 2019. The changing trends were described by estimated annual percentage changes (EAPCs). RESULTS: Globally, in 2019, the ASIR and age-standardised DALYs rates of TIs were 134 6.06/100 000 (95% UI 11 42.6/100 000-157 5.57/100 000) and 97 7.91/100 000 (86 8.91/100 000-107 6.81/100 000), respectively. From 1990 to 2019, the global ASIR of TIs presented significant upwards trends with the EAPC (0.25%, 95% CI 0.19% to 0.31%), and it was significantly increased in the age groups of 15-49 (0.37%, 95% CI 0.29% to 0.45%), 50-69 (0.40%, 95% CI 0.36% to 0.44%) and 70+ (0.22%, 95% CI 0.17% to 0.28%). Prominent increases in ASIR were detected in middle-SDI areas (0.72%, 95% CI 0.57% to 0.87%), low-middle SDI areas (0.66%, 95% CI 0.59% to 0.72%) and low-SDI areas (0.21%, 95% CI 0.17% to 0.26%). The global age-standardised DALYs rate presented downwards trends with the EAPC (-1.27%, 95% CI -1.35% to -1.2%), and it was significantly decreased in all age groups and SDI areas. CONCLUSION: Globally, TIs still cause a serious burden, and the incidence has significantly increased, especially in people above the age of 14 and in middle-SDI and low-SDI areas, thus necessitating more attention and health interventions.

FOXA1-induced LINC00621 promotes lung adenocarcinoma progression via activating the TGF-ß signaling pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is highly malignant and associated with poor prognoses in patients worldwide. There has been widespread recognition that lncRNAs are tightly linked to LUAD tumorigenesis and development. Here, we identified that the LINC00621 level was increased in LUAD tissues and concerned with the poor prognoses in LUAD patients. METHODS: Bioinformatical analysis and RT-qPCR determined the level of LINC00621 in LUAD tissues and cell lines. The admeasurement of the proliferation, migration, and invasion abilities of LUAD cells was utilized in the CCK8 and Transwell formulas. Luciferase reporter assay was used to corroborate the downstream target genes of LINC00621. The phosphorylated SMAD3 protein was tested by Western blotting assay. The impression of LINC00621 knockdown on LUAD tumor growth and metastasis put into effect by murine models. ChIP-qPCR assay was carried out to verify the transcriptional regulation by FOXA1 on LINC00621. RESULTS: In vitro, the knockdown of LINC00621 significantly reduced the proliferative, migrating, and invasive abilities, the same was true for tumorigenesis and metastasis in vivo. MiR-34a-5p as a straight target of LINC00621 was ascertained, and LUAD patients with inferior miR-34a-5p levels had undesirable prognoses. Furthermore, TGFBR1 is an immediate and functional connection site of miR-34a-5p. Collectively, LINC00621 can sponge miR-34a-5p and upregulate TGFBR1 levels, which further sensitized TGF-ß signaling pathway. Finally, it was revealed that FOXA1 transcriptionally upregulated LINC00621. CONCLUSION: This study uncovered that FOXA1-induced LINC00621 promotes LUAD progression via the miR-34a-5p/TGFBR1/TGF-ß axis, and is one novel therapeutic target that may be used in LUAD treatment.

Effects of the digital economy on carbon emissions in China: an analysis based on different innovation paths.

As the digital economy grows rapidly around the world, how would it impact carbon emissions? This paper discusses this issue from the perspective of heterogeneous innovation. Based on the panel data of 284 cities in China from 2011 to 2020, this paper empirically examines the impact of the digital economy on carbon emissions as well as the mediating and threshold effects of different innovation modes. The study finds that the digital economy can significantly reduce carbon emissions; this conclusion holds after a series of robustness tests. Independent innovation and imitative innovation are important channels through which the digital economy affects carbon emissions, but technological introduction is not an effective way. For regions with high levels of financial investment in science and innovative talents, the reduction in carbon emissions from the digital economy is more significant. Further research shows that the effect of the digital economy on carbon emissions has a threshold feature, with an inverted U-shaped relationship between the two, and that an increase in autonomous innovation and imitation innovation can enhance the digital economy's carbon reduction effect. Therefore, it is necessary to strengthen the capacity of independent innovation and imitation innovation to exploit the carbon-cutting effect of the digital economy.

The effects and drivers of green financial reform in promoting environmentally-biased technological progress.

Promoting green financial reform is an important measure to support environmentally-biased technological progress (EBTP) and achieve sustainable economic and social development. Although China launched a green finance reform and innovation pilot zone (GFRIPZ) policy in 2017, little is known about whether and how such a policy affects EBTP. Based on mathematical deduction, this paper studies the mechanism through which green financial reform influences EBTP. The analysis employs panel data of Chinese prefecture-level cities and a generalized synthetic control method to examine the policy effect of the establishment of GFRIPZ in EBTP. It is found that establishing GFRIPZ significantly promotes EBTP, and that the policy effect shows "ahead-of-policy" and dynamically increasing features. Potential mechanisms reside in the pilot policy's easing of financing constraints and upgrading of industrial structure. Further heterogeneity analyses reveal that great disparities exist in the policy effects of different pilot zones, with a steadily increasing policy effect in Zhejiang and Guangdong, a lagging policy effect in Jiangxi and Guizhou, and an inverse U-shaped policy effect in Xinjiang. Policy effects are much stronger in regions with a higher degree of marketization and a higher level of attention to education. Additional tests of economic performance indicate that the pilot policy, interweaved with its driving effect on EBTP, is conducive to promoting an energy-conservation and low-carbon-energy transition. The findings shed light on applying green financial reform to encourage environment-friendly technological research and development.

Characterization of Arnebia euchroma PGT homologs involved in the biosynthesis of shikonin.

Shikonin is a red naphthoquinone natural product from plants with high economical and medical values. The para-hydroxybenzoic acid geranyltransferase (PGT) catalyzes the key regulatory step of shikonin biosynthesis. PGTs from Lithospermum erythrorhizon have been well-characterized and used in industrial shikonin production. However, its perennial medicinal plant Arnebia euchroma accumulates much more pigment and the underlying mechanism remains obscure. Here, we discovered and characterized the different isoforms of AePGTs. Phylogenetic study and structure modeling suggested that the N-terminal of AePGT6 contributed to its highest activity among 7 AePGTs. Indeed, AePGT2 and AePGT3 fused with 60 amino acids from the N-terminal of AePGT6 showed even higher activity than AePGT6, while native AePGT2 and AePGT3 don't have catalytic activity. Our result not only provided a mechanistic explanation of high shikonin contents in Arnebia euchroma but also engineered a best-performing PGT to achieve the highest-to-date production of 3-geranyl-4-hydroxybenzoate acid, an intermedium of shikonin.

Structure-Based Mechanistic Insights into ColB1, a Flavoprotein Functioning in-trans in the 2,2'-Bipyridine Assembly Line for Cysteine Dehydrogenation.

The recruitment of trans-acting enzymes by nonribosomal peptide synthetase (NRPS) assembly line is rarely reported. ColB1 is a flavin-dependent dehydrogenase that is recruited by an NRPS terminal condensation domain (Ct domain) and catalyzes peptidyl carrier protein (PCP)-tethered cysteine dehydrogenation in collismycin biosynthesis. We here report the crystal structure of ColB1 complexed with FAD and reveal a typical structural fold of acyl-CoA dehydrogenases (ACADs). However, ColB1 shows distinct structural features from ACADs in substrate recognition both at the entrance of and inside the active site. Site-directed mutagenesis and substrate modeling establish a Glu393-mediated catalytic mechanism, by which the cysteine substrate is sandwiched between Glu393 and FAD to facilitate Cα proton abstraction and Cß hydride migration. A ColB1-PCP-Ct complex model is generated, providing structural basis for the unique recruitment interactions between ColB1 and the associated NRPS. These results add insights into the mechanisms by which trans-acting enzymes function in an assembly line.

Analgesic effectiveness of preoperative ultrasound-guided erector spinae plane block versus paravertebral nerve block for breast surgery: A systematic review and meta-analysis of four randomized controlled trials.

OBJECTIVE: Our meta-analysis aimed to compare the analgesic effectiveness of ultrasound-guided preoperative erector spinae plane block (ESPB) versus paravertebral nerve block (PVB) in breast surgery. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for randomized controlled trials (RCTs) between January 1, 1980 and April 31, 2021. The primary endpoints were perioperative pain score, analgesic consumption, and assessment of the block procedure. The secondary endpoints were intraoperative hemodynamic response, duration of surgery, postoperative antiemetic consumption, and adverse effects. RESULTS: Four RCTs comprised a total of 310 patients were included in our meta-analysis. No significant differences in the perioperative pain score and analgesic consumption were observed between ESPB and PVB in the operating room, post-anesthesia care unit (PACU), and ward (at 1, 16, 12, and 24 h), and the morning of postoperative day 1 (POD1) (all p > 0.05). Similarly, no significant differences in the duration of block, time to first analgesic, hemodynamic response, duration of surgery, postoperative antiemetic consumption, and adverse effects were observed (all p > 0.05). However, our meta-analysis revealed that ultrasound-guided preoperative ESPB significantly reduced the duration of procedure time and frequency of guidance interventions, as well as increased the block success rate among residents (all p < 0.05). CONCLUSIONS: Both ultrasound-guided preoperative ESPB and PVB showed comparable analgesic effects in patients undergoing breast surgery. However, with a significantly shorter procedure time and higher block success rate, our findings suggest that ESPB may be a simple alternative to PVB in breast surgery.

Biochemical and Morphological Changes Triggered by Nitrogen Stress in the Oleaginous Microalga Chlorella vulgaris.

Oleaginous microalgae have been considered promising sources of biodiesel due to their high lipid content. Nitrogen limitation/starvation is one of the most prominent strategies to induce lipid accumulation in microalgae. Nonetheless, despite numerous studies, the mechanism underlying this approach is not well understood. The aim of this study was to investigate the effect of nitrogen limitation and starvation on biochemical and morphological changes in the microalga Chlorella vulgaris FACHB-1068, thereby obtaining the optimal nitrogen stress strategy for maximizing the lipid productivity of microalgal biomass. The results showed that nitrogen limitation (nitrate concentration < 21.66 mg/L) and starvation enhanced the lipid content but generally decreased the biomass productivity, pigment concentration, and protein content in algal cells. Comparatively, 3-day nitrogen starvation was found to be a more suitable strategy to produce lipid-rich biomass. It resulted in an increased biomass production and satisfactory lipid content of 266 mg/L and 31.33%, respectively. Besides, nitrogen starvation caused significant changes in cell morphology, with an increase in numbers and total size of lipid droplets and starch granules. Under nitrogen starvation, saturated fatty acids (C-16:0, C-20:0, and C-18:0) accounted for the majority of the total fatty acids (~80%), making C. vulgaris FACHB-1068 a potential feedstock for biodiesel production. Our work may contribute to a better understanding of the biochemical and morphological changes in microalgae under nitrogen stress. Besides, our work may provide valuable information on increasing the lipid productivity of oleaginous microalgae by regulating nitrogen supply.

Layer-by-Layer Engineered All-Liquid Microfluidic Chips for Enzyme Immobilization.

Enzyme immobilization in the confines of microfluidic chips, that promote enzyme activity and stability, has become a powerful strategy to enhance biocatalysis and biomass conversion. Here, based on a newly developed all-liquid microfluidic chip, fabricated by the interfacial assembly of nanoparticle surfactants (NPSs) in a biphasic system, a layer-by-layer assembly strategy to generate polysaccharide multilayers on the surface of a microchannel, greatly enhancing the mechanical properties of the microchannel and offering a biocompatible microenvironment for enzyme immobilization, is presented. Using horseradish peroxidase and glucose oxidase as model enzymes, all-liquid microfluidic enzymatic and cascade reactors have been constructed and the crucial role of polysaccharide multilayers on enhancing the enzyme loading and catalytic efficiency is demonstrated.

Increased Expression of CD95 in CD4+ Effector Memory T Cells Promotes Th17 Response in Patients with Myasthenia Gravis.

Emerging data have revealed that CD95 can evoke non-apoptotic signals, thereby promoting pro-inflammatory functions that link to the severity of autoimmune disorders. Here, we reported that the expression of CD95 in CD4+ effector memory T (CD4+ TEM) cells was increased in myasthenia gravis (MG) patients. We also found increased expression of CD95 in CD4+ TEM cells from MG patients correlated positively with clinical severity scores (QMGs), serum IL-17 levels and plasma cells (PCs) frequencies. Conventional treatment, such as glucocorticoid, could down-regulate the expression of CD95 in CD4+ TEM cells, QMGs, serum IL-17 levels and PCs frequencies from MG patients. In vitro, low-dose of agonistic anti-CD95 mAb could promote Th17 cell development. This effect was reversed by CD95 siRNA. Moverover, CD95 stimulation induced the phosphorylation of p38 and Erk1/2 and Th17 cell differentiation, and p38 specific inhibitor SB203580 or Erk1/2 specific inhibitor PD98059 could induce opposite changes. However, SB203580 or PD98059 do not abrogate the increase of CCR6+IL-17A+ cells, ROR-γt and IL-17 expression induced by CD95 triggering relatively to each corresponding control. This suggests that p38 and Erk1/2 MAPK pathway plays a role in expression of CCR6+IL-17A+ cells, ROR-γt and IL-17, but not in their increase induced by CD95 triggering. Taken together, this study revealed that increased expression of CD95 in CD4+ TEM cells promotes Th17 response under the microenvironment of MG.

Exploration of Microalgal Species for Nutrient Removal from Anaerobically Digested Swine Wastewater and Potential Lipids Production.

Bio-treatment of anaerobically treated swine wastewater (ADSW) mediated by microalgae has been deemed as a promising strategy. In the present study, six microalgal strains were used to conduct batch experiments in 0~100% ADSW in order to evaluate their potentials for nutrient removal and biodiesel production. Two strains, Chlorella vulgaris FACHB-8 and Chlorella sp. FACHB-31, were selected based on their better growth performances, higher tolerance to wastewater (up to 100%), and better nutrient removal abilities. The capacity of each strain to remove TN, TP, NH4+-N, as well as lipid production and biomass composition in 100% ADSW were further examined. After 15 days of culture, 87.68~89.85%, 92.61~93.68%, and 97.02~97.86% of the nitrogen, phosphorus, and ammonia nitrogen were removed by Chlorella sp. FACHB-31 and C. vulgaris FACHB-8. Their lipid content and lipid productivities were 29.63~33.33% and 18.91~23.10 mg L-1 d-1, respectively. Proteins were both the major biomass fraction followed by lipids and then carbohydrates. Their fatty acid profiles both mainly consisted of C-16:0, C-18:1, C-18:0, and C-18:2. Taken together, our results suggest that C. vulgaris FACHB-8 and Chlorella sp. FACHB-31 are potential candidates for biodiesel production by using ADSW as a good feedstock.

Rational generation of lasso peptides based on biosynthetic gene mutations and site-selective chemical modifications.

Lasso peptides are a unique family of natural products whose structures feature a specific threaded fold, which confers these peptides the resistance to thermal and proteolytic degradation. This stability gives lasso peptides excellent pharmacokinetic properties, which together with their diverse reported bioactivities have garnered extensive attention because of their drug development potential. Notably, the threaded fold has proven quite inaccessible by chemical synthesis, which has hindered efficient generation of structurally diverse lasso peptides. We herein report the discovery of a new lasso peptide stlassin (1) by gene activation based on a Streptomyces heterologous expression system. Site-directed mutagenesis on the precursor peptide-encoding gene is carried out systematically, generating 17 stlassin derivatives (2-17 and 21) with residue-replacements at specific positions of 1. The solution NMR structures of 1, 3, 4, 14 and 16 are determined, supporting structural comparisons that ultimately enabled the rational production of disulfide bond-containing derivatives 18 and 19, whose structures do not belong to any of the four classes currently used to classify lasso peptides. Several site-selective chemical modifications are first applied on 16 and 21, efficiently generating new derivatives (20, 22-27) whose structures bear various decorations beyond the peptidyl monotonicity. The high production yields of these stlassin derivatives facilitate biological assays, which show that 1, 4, 16, 20, 21 and 24 possess antagonistic activities against the binding of lipopolysaccharides to toll-like receptor 4 (TLR4). These results demonstrate proof-of-concept for the combined mutational/chemical generation of lasso peptide libraries to support drug lead development.