Arsenic aggravates the progression of diabetic nephropathy through miRNA-mRNA-autophagy axis.

Environmental factors play an important role in the progression of diabetic nephropathy (DN), and previous study has shown that arsenic exposure can promote kidney damage in DN rats, however there is no relevant mechanism study so far. In this study, an arsenic-exposed (10 mg/L and 25 mg/L) DN mouse model was established through drinking water for 14 weeks. The results showed that 25 mg/L arsenic exposure increased the renal fibrosis in DN mice significantly, and urinary mAlb level increased with the increasing of arsenic exposure level. Transcriptome sequencing showed that autophagy-related pathways were significantly activated under the exposure dose of 25 mg/L, and levels of Beclin1 and p-ATG16L1/ATG16L1 were significantly higher in the 25 mg/L arsenic group compared to the control group. Silico analysis predicted the microRNAs those could regulate the hub genes of Mapk1, Rhoa and Cdc42, and dual-luciferase gene reporter assay was used to verify the targeted binding between these mRNAs and microRNAs. Our results suggested that high arsenic exposure could aggravate the progression of DN by altering autophagy, the miRNA-mRNA axles of let-7a-1-3p, let-7b-3p, let-7f-1-3p, miR-98-3p/Cdc42, Mapk1, Rhoa, could be considered promising targets to explore the mechanisms and therapeutic measures of DN after exposure to high levels of arsenic.

Metabolic and Bioprocess Engineering of Clostridium tyrobutyricum for Butyl Butyrate Production on Xylose and Shrimp Shell Waste.

Microbial conversion of agri-food waste to valuable compounds offers a sustainable route to develop the bioeconomy and contribute to sustainable biorefinery. Clostridium tyrobutyricum displays a series of native traits suitable for high productivity conversion of agri-food waste, which make it a promising host for the production of various compounds, such as the short-chain fatty acids and their derivative esters products. In this study, a butanol synthetic pathway was constructed in C. tyrobutyricum, and then efficient butyl butyrate production through in situ esterification was achieved by the supplementation of lipase into the fermentation. The butyryl-CoA/acyl-CoA transferase (cat1) was overexpressed to balance the ratio between precursors butyrate and butanol. Then, a suitable fermentation medium for butyl butyrate production was obtained with xylose as the sole carbon source and shrimp shell waste as the sole nitrogen source. Ultimately, 5.9 g/L of butyl butyrate with a selectivity of 100%, and a productivity of 0.03 g/L·h was achieved under xylose and shrimp shell waste with batch fermentation in a 5 L bioreactor. Transcriptome analyses exhibited an increase in the expression of genes related to the xylose metabolism, nitrogen metabolism, and amino acid metabolism and transport, which reveal the mechanism for the synergistic utilization of xylose and shrimp shell waste. This study presents a novel approach for utilizing xylose and shrimp shell waste to produce butyl butyrate by using an anaerobic fermentative platform based on C. tyrobutyricum. This innovative fermentation medium could save the cost of nitrogen sources (~97%) and open up possibilities for converting agri-food waste into other high-value products.

Composite of CoS1.97 nanoparticles decorated CuS hollow cubes with rGO as thin film electrode for high-performance all solid flexible supercapacitors.

Stretchable flexible thin-film electrodes are extensively explored for developing new wearable energy storage devices. However, traditional carbon-based materials used in such independent electrodes have limited practical applications owing to their low energy storage capacity and energy density. To address this, a unique structure and remarkable mechanical stability thin-film flexible positive electrode comprising CoS1.97 nanoparticles decorated hollow CuS cubes and reduced graphene oxide (rGO), hereinafter referred to as CCSrGO, is prepared. Transition metal sulfide CoS1.97 and CuS shows high energy density owing to the synergistic effects of its active components. The electrode can simultaneously meet the high-energy density and safety requirements of new wearable energy storage devices. The electrode has excellent electrochemical performance (1380 F/g at 1 A/g) and ideal capacitance retention (93.8 % after 10,000 cycles) owing to its unique three-dimensional hollow structure and polymetallic synergies between copper and cobalt elements, which are attributed to their different energy storage mechanisms. Furthermore, a flexible asymmetric supercapacitor (FASC) was constructed using CCSrGO as the positive electrode and rGO as the negative electrode (CCSrGO//rGO), which delivers an energy density of 100 Wh kg-1 and a corresponding power density of 2663 W kg-1 within a voltage window of 0-1.5 V. The resulting FASC can power a light-emitting diode (LED) at different bending and twisting angles, exerting little effect on the capacitance. Therefore, the prepared CCSrGO//rGO FASC devices show great application prospects in energy storage.

Comparison of clinical outcomes between transthoracic echocardiography- and X-ray-guided left bundle branch pacing for bradycardia: A randomized controlled trial.

INTRODUCTION: Left bundle branch pacing (LBBP) is a physiological pacing modality. However, the long procedure and fluoroscopy time of LBBP is still a problem. This study aims to compare the clinical outcomes between transthoracic echocardiography (TTE)- and X-ray-guided LBBP. METHODS: This is a single-center, prospective, randomized controlled study. Consecutive patients who underwent LBBP in our team from June 2022 to November 2022 were enrolled. Procedure and fluoroscopy time, pacing parameters, electrophysiological and echocardiographic characteristics, as well as complications were recorded at implantation and during follow-up. RESULTS: In this study, 60 patients were enrolled and divided into two groups: 30 patients were allocated to the X-ray group and the remaining 30 to the TTE group. There was no significant difference in the success rate between the two groups (86.7% vs. 76.7%, p = .317). The procedure time of TTE group was comparable to that of the X-ray group (9.0 vs. 12.0 min, p = .063). However, the fluoroscopy time in the TTE group was significantly lower than that of the X-ray group (2.5 vs. 5.0 min, p = .002). There were no statistically significant differences in pacing parameters, electrophysiological and echocardiographic characteristics, or complications between the two groups at implantation and during follow-up. CONCLUSION: TTE-guided LBBP is a feasible and safe method. Compared with X-ray, TTE showed a comparable success rate and procedure time, but it could significantly reduce the fluoroscopy time of LBBP.

AMPKα is active in autophagy of endothelial cells in arsenic-induced vascular endothelial dysfunction by regulating mTORC1/p70S6K/ULK1.

Cardiovascular disease (CVD) is the most common cause of death, environmental factors, such as arsenic, playing an important role in the progress of CVD. Vascular endothelial dysfunction (VED) is a crucial early feature for CVD, inorganic arsenic (iAs) can induce autophagy in various cells. However, the role of endothelial autophagy has rarely been studied in VED triggered by arsenic. Total of one hundred and twenty healthy male C57BL/6J mice weighing 18-22 g were randomly divided into an arsenic-exposure group and a control group for 3, 6, 9, and 12 weeks. The results showed that, independent of the exposure period, autophagy markers of p-ATG16L1 levels and Beclin 1 contents in the aortic arch endothelium increased significantly compared with those of the corresponding control group. And different exposure duration decreased NO contents in the serum significantly. Combined with the histological changes that endothelial injury aggravated gradually with the increasing exposure period, suggesting that under exposure to iAs over 9 weeks, VED was remarkably induced, and consistant high levels of endothelial autophagy may play an important role. Additionally, levels of p-AMPKα/AMPKα increased significantly and p-mTORC1/mTORC1 levels decreased remarkably in the aortic arch endothelium. Then, a NaAsO2-induced-VED in vitro model was used to explore the mechanism of arsenic-induced endothelial autophagy. Similarly, p-AMPKα/AMPKα level significantly increased, and p-mTORC1/mTORC1 level remarkably decreased induced by 30 µmol/L NaAsO2 in HUAECs. Further, an AMPK inhibitor (Compound C) pre-treatment prior to arsenic exposure reversed the increased autophagy level, and alleviated the endothelial dysfunction in HUVECs, as shown by the significant increase in the intracellular NO content and the cell vitality. Mechanistically, we revealed that AMPKα is active in autophagy of endothelial cells in arsenic-induced VED by regulating mTORC1/p70S6K/ULK1. The present study provide a new promising target for prevention and control arsenic-associated CVD.

Endogenous CRISPR-Cas mediated in situ genome editing: State-of-the-art and the road ahead for engineering prokaryotes.

The CRISPR-Cas systems have shown tremendous promise as heterologous tools for genome editing in various prokaryotes. However, the perturbation of DNA homeostasis and the inherent toxicity of Cas9/12a proteins could easily lead to cell death, which led to the development of endogenous CRISPR-Cas systems. Programming the widespread endogenous CRISPR-Cas systems for in situ genome editing represents a promising tool in prokaryotes, especially in genetically intractable species. Here, this review briefly summarizes the advances of endogenous CRISPR-Cas-mediated genome editing, covering aspects of establishing and optimizing the genetic tools. In particular, this review presents the application of different types of endogenous CRISPR-Cas tools for strain engineering, including genome editing and genetic regulation. Notably, this review also provides a detailed discussion of the transposon-associated CRISPR-Cas systems, and the programmable RNA-guided transposition using endogenous CRISPR-Cas systems to enable editing of microbial communities for understanding and control. Therefore, they will be a powerful tool for targeted genetic manipulation. Overall, this review will not only facilitate the development of standard genetic manipulation tools for non-model prokaryotes but will also enable more non-model prokaryotes to be genetically tractable.

Reducing spatial resolution increased net primary productivity prediction of terrestrial ecosystems: A Random Forest approach.

Net primary production (NPP) is a pivotal component of the terrestrial carbon dynamic, as it directly contributes to the sequestration of atmospheric carbon by vegetation. However, significant variations and uncertainties persist in both the total amount and spatiotemporal patterns of terrestrial NPP, primarily stemming from discrepancies among datasets, modeling approaches, and spatial resolutions. In order to assess the influence of different spatial resolutions on global NPP, we employed a random forest (RF) model using a global observational dataset to predict NPP at 0.05°, 0.25°, and 0.5° resolutions. Our results showed that (1) the RF model performed satisfactorily with modeling efficiencies of 0.53-0.55 for the three respective resolutions; (2) NPP exhibited similar spatial patterns and interannual variation trends at different resolutions; (3) intriguingly, total global NPP varied greatly across different spatial resolutions, amounting 57.3 ± 3.07 for 0.05°, 61.46 ± 3.27 for 0.25°, and 66.5 ± 3.42 Pg C yr-1 for 0.5°. Such differences may be associated with the resolution transformation of the input variables when resampling from finer to coarser resolution, which significantly increased the spatial and temporal variation characteristics, particularly in regions within the southern hemisphere such as Africa, South America, and Australia. Therefore, our study introduces a new concept emphasizing the importance of selecting an appropriate spatial resolution when modeling carbon fluxes, with potential applications in establishing benchmarks for global biogeochemical models.

Chemical-induced epigenome resetting for regeneration program activation in human cells.

Human somatic cells can be reprogrammed to pluripotent stem cells by small molecules through an intermediate stage with a regeneration signature, but how this regeneration state is induced remains largely unknown. Here, through integrated single-cell analysis of transcriptome, we demonstrate that the pathway of human chemical reprogramming with regeneration state is distinct from that of transcription-factor-mediated reprogramming. Time-course construction of chromatin landscapes unveils hierarchical histone modification remodeling underlying the regeneration program, which involved sequential enhancer recommissioning and mirrored the reversal process of regeneration potential lost in organisms as they mature. In addition, LEF1 is identified as a key upstream regulator for regeneration gene program activation. Furthermore, we reveal that regeneration program activation requires sequential enhancer silencing of somatic and proinflammatory programs. Altogether, chemical reprogramming resets the epigenome through reversal of the loss of natural regeneration, representing a distinct concept for cellular reprogramming and advancing the development of regenerative therapeutic strategies.

Highly efficient and rapid generation of human pluripotent stem cells by chemical reprogramming.

We recently demonstrated the chemical reprogramming of human somatic cells to pluripotent stem cells (hCiPSCs), which provides a robust approach for cell fate manipulation. However, the utility of this chemical approach is currently hampered by slow kinetics. Here, by screening for small molecule boosters and systematically optimizing the original condition, we have established a robust, chemically defined reprogramming protocol, which greatly shortens the induction time from ∼50 days to a minimum of 16 days and enables highly reproducible and efficient generation of hCiPSCs from all 17 tested donors. We found that this optimized protocol enabled a more direct reprogramming process by promoting cell proliferation and oxidative phosphorylation metabolic activities at the early stage. Our results highlight a distinct chemical reprogramming pathway that leads to a shortcut for the generation of human pluripotent stem cells, which represents a powerful strategy for human cell fate manipulation.

Controls and variability of soil respiration temperature sensitivity across China.

Understanding the temperature sensitivity (Q10) of soil respiration is critical for benchmarking the potential intensity of regional and global terrestrial soil carbon fluxes-climate feedbacks. Although field observations have demonstrated the strong spatial heterogeneity of Q10, a significant knowledge gap still exists regarding to the factors driving spatial and temporal variabilities of Q10 at regional scales. Therefore, we used a machine learning approach to predict Q10 from 1994 to 2016 with a spatial resolution of 1 km across China from 515 field observations at 5 cm soil depth using climate, soil and vegetation variables. Predicted Q10 varied from 1.54 to 4.17, with an area-weighted average of 2.52. There was no significant temporal trend for Q10 (p = 0.32), but annual vegetation production (indicated by normalized difference vegetation index, NDVI) was positively correlated to it (p < 0.01). Spatially, soil organic carbon (SOC) was the most important driving factor in 62 % of the land area across China, and varied greatly, demonstrating soil controls on the spatial pattern of Q10. These findings highlighted different environmental controls on the spatial and temporal pattern of soil respiration Q10, which should be considered to improve global biogeochemical models used to predict the spatial and temporal patterns of soil carbon fluxes to ongoing climate change.

Effects of biochar addition on nitrous oxide emission during soil freeze-thaw cycles.

Biochar applied to soil can reduce nitrous oxide (N2O) emissions produced by freeze-thaw processes. Nonetheless, how biochar modification affects N2O emissions during freeze-thaw cycles is not completely clear. In our research, during freeze-thaw cycles, microcosm experiments were conducted to investigate the effects of maize straw biochar (MB) or rice straw biochar (RB) addition on soil N2O emissions under different water conditions. The N2O emissions peaked at the initial stage of thawing in all the soils, and the total N2O emissions were considerably greater in the flooded soils than in the nonflooded soils. Compared with the soils without biochar addition, RB and MB amendments inhibited N2O emissions by 69 and 67%, respectively. Moreover, after biochar addition, the abundance of AOB amoA genes decreased by 9-13%. Biochar addition significantly decreased the content of microbial biomass nitrogen (MBN) in flooded soil during thawing, which was significantly correlated with N2O emissions and nitrification and denitrification communities. The PLS-PM further revealed that biochar can inhibit the production and emission of soil N2O by reducing soil MBN during soil thawing. In addition, soil moisture directly significantly affects N2O emissions and indirectly affects N2O emissions through its influence on soil physicochemical properties. Our results revealed the important function of biochar in decreasing the emission of N2O in flooded soil during freeze-thaw cycles.

Functional Characterization of Clostridium tyrobutyricum L319: A Promising Next-Generation Probiotic for Short-Chain Fatty Acid Production.

Probiotics contribute a lot to human health and the occurrence of diseases. Correspondingly, probiotics' safety evaluation and probiotic properties have received increasing attention in the food industry and disease treatment. Clostridium tyrobutyricum L319 is a short-chain fatty acid (SCFA)-producing strain isolated from Grana Padano cheese with a blowing defect. Our previous study has shown its safety at the genomic level. This study focused more on the safety evaluation and probiotic properties in vitro. According to the results, this strain has no potential virulence factors or the possibility of antibiotic resistance genes propagation. It also fulfilled several criteria to be used as a probiotic, including significant hydrophobicity under an acidic condition (pH 5.0) and resistance to simulate gastric juice and intestinal juice. Additionally, this strain was found to be tolerant to the harsh conditions of the external environment, including resistance to low (20°C) and high (50°C) temperatures, high salts (3% NaCl), and low pH (pH 5.0). Finally, we found that this strain could ferment prebiotics, such as chito-oligosaccharides, to produce SCFAs. It exhibited excellent growth performance whether using chito-oligosaccharide as a sole carbon source or combining glucose as the mixed carbon source. Furthermore, chito-oligosaccharide and glucose (1:1) mixed carbon sources were the optimal strategy for the production of SCFAs. Our findings demonstrated that this strain might be considered a promising candidate for future use as a probiotic to promote health benefits.

Clostridium as microbial cell factory to enable the sustainable utilization of three generations of feedstocks.

The sustainable production of chemicals and biofuels from non-fossil carbon sources is considered key to reducing greenhouse gas (GHG) emissions. Clostridium sp. can convert various substrates, including the 1st-generation (biomass crops), the 2nd-generation (lignocellulosic biomass), and the 3rd-generation (C1 gases) feedstocks, into high-value products, which makes Clostridia attractive for biorefinery applications. However, the complexity of lignocellulosic catabolism and C1 gas utilization make it difficult to construct efficient production routes. Accordingly, this review highlights the advances in the development of three generations of feedstocks with Clostridia as cell factories. At the same time, more attention was given to using agro-industrial wastes (lignocelluloses and C1 gases) as the feedstocks, for which metabolic and process engineering efforts were comprehensively analyzed. In addition, the challenges of using agro-industrial wastes are also discussed. Lastly, several new synthetic biology tools and regulatory strategies are emphasized as promising technologies to be developed to address the aforementioned challenges in Clostridia and realize the efficient utilization of agro-industrial wastes.

Sequence, structure, and function of the Dps DNA-binding protein from Deinococcus wulumuqiensis R12.

Deinococcus wulumuqiensis R12, which was isolated from arid irradiated soil in Xinjiang province of China, belongs to a genus that is well-known for its extreme resistance to ionizing radiation and oxidative stress. The DNA-binding protein Dps has been studied for its great contribution to oxidative resistance. To explore the role of Dps in D. wulumuqiensis R12, the Dps sequence and homology-modeled structure were analyzed. In addition, the dps gene was knocked out and proteomics was used to verify the functions of Dps in D. wulumuqiensis R12. Docking data and DNA binding experiments in vitro showed that the R12 Dps protein has a better DNA binding ability than the Dps1 protein from D. radiodurans R1. When the dps gene was deleted in D. wulumuqiensis R12, its resistance to H2O2 and UV rays was greatly reduced, and the cell envelope was destroyed by H2O2 treatment. Additionally, the qRT-PCR and proteomics data suggested that when the dps gene was deleted, the catalase gene was significantly down-regulated. The proteomics data indicated that the metabolism, transport and oxidation-reduction processes of D. wulumuqiensis R12 were down-regulated after the deletion of the dps gene. Overall, the data conformed that Dps protein plays an important role in D. wulumuqiensis R12.

TiO2 nanoparticles exert an adverse effect on aquatic microbial communities.

Titanium dioxide nanoparticle (n-TiO2) is a widely used nanomaterial, which is inevitably released as a residue into aquatic ecosystems during material production and usage. However, the effects of n-TiO2 on aquatic microbial communities have not been completely elucidated. This study examined the toxic effects of n-TiO2 on eukaryotic and prokaryotic microbial communities in freshwater environments. We determined that n-TiO2 had a greater inhibitory effect on the growth of eukaryotic algae than cyanobacteria in monocultures. A similar phenomenon was observed in a microcosm experiment, revealing that n-TiO2 slightly reduced the content of chlorophyll-a but evidently increased the phycocyanin content. Moreover, the alpha diversity of the eukaryotic community was not affected, whereas its beta diversity increased with exposure to n-TiO2. Although n-TiO2 altered the composition of freshwater microbial communities, it did not change the functions of the prokaryotic community, which might be attributed to the functional redundancy of microbiota. Co-occurrence network analysis indicated that n-TiO2 destabilized the freshwater community, especially the eukaryotic community, and potentially disturbed the aquatic ecosystem. Our study revealed that the ecological risk of n-TiO2 on aquatic microbial communities is complex; hence, rational utilization of n-TiO2 should be emphasized.

A Comparative Study on the Mechanical Properties and Microstructure of Cement-Based Materials by Direct Electric Curing and Steam Curing.

Direct electric curing (EC) is a new green curing method for cement-based materials that improves the early mechanical properties via the uniform high temperature produced by Joule heating. To understand the effects of EC and steam curing (SC) on the mechanical properties and microstructure of cement-based materials, the mortar was cured at different temperature-controlled curing regimes (40 °C, 60 °C, and 80 °C). Meanwhile, the mechanical properties, hydrates and pore structures of the specimens were investigated. The energy consumption of the curing methods was compared. The results showed that the EC specimens had higher and more stable growth of mechanical strength. The hydration degree and products of EC samples were similar to that of SC samples. However, the pore structure of EC specimens was finer than that of SC specimens at different curing ages. Moreover, the energy consumption of EC was much lower than that of SC. This study provides an important technical support for the EC in the production of energy-saving and high early-strength concrete precast components.

Nano-Sized Polystyrene at 1 mg/L Concentrations Does Not Show Strong Disturbance on the Freshwater Microbial Community.

In recent years, microplastics and nanoplastics have gained public attention, but their impacts on the freshwater microbial communities is rarely evaluated. In this study, the effects of 1 mg/L nano-sized polystyrene (nPS) and its modified forms (carboxyl-modified and amino-modified nPS) on the structures and functions of freshwater microbial community were determined. The nPS were found to slightly reduce the chlorophyll-a and increase the phycocyanin contents of freshwater microbial communities. Moreover, the richness of the microbial communities temporarily decreased during this process, while their diversity remained uninfluenced by treatment with nPS. Although the three tested nPS types were found to disturb the compositions of both the prokaryotic and eukaryotic communities to some degree, they did not affect the functions of freshwater bacterial communities significantly due to functional redundancy. Our study demonstrated that the ecotoxicities of the nPS itself were found to be lower than what is generally expected.

Fabrication and characterization of magnetically responsive Fe3O4@TiO2 core-shell adsorbent for enhanced thallium removal.

Thallium (Tl) contamination in natural waters can pose a severe risk to human health. In this study, a magnetically responsive Fe3O4@TiO2 core-shell adsorbent was developed for the effective removal of thallium(I) from water. The isoelectric point of the adsorbent surface was decreased from 6.0 to 4.8 due to the loading of nano-sized TiO2, leading to an enhanced electrostatic interaction between the adsorbent and Tl(I) ions in a wider pH range. The Fe3O4@TiO2 magnetic adsorbent exhibited a threefold higher BET specific surface area compared to pristine Fe3O4 particles. The kinetics study showed that approximately 82% of the maximum Tl(I) loading amount could be achieved within 30 min at the initial Tl(I) concentration of 8 mg/L and adsorbent dosage of 0.1 g/L. The adsorption of Tl(I) was significantly increased with increasing solution pH. The experimental data was better fitted by the Langmuir and Temkin isotherms than the Freundlich isotherm and the maximum adsorption capacity of the magnetic adsorbent was 101.5 mg/g at pH 7.0. The interference of co-existing cations in the Tl(I) adsorption followed the subsequence: Cu2+ > Mg2+ > Ca2+ > Na+. The hydroxyl groups bonded on titanium atoms might play a key role in the uptake of Tl(I) ions. During the adsorption, the Tl(I) ions can be effectively adsorbed on the adsorbent surface via the formation of Ti-O-Tl linkages. Graphical Abstract.

Understanding the Hierarchical Relationships in Female Sex Workers' Social Networks Based on Knowledge, Attitude, and Practice.

Female sex workers (FSWs) represent a high-risk population for HIV infection and transmission. In general, their fellow FSWs (peers) also play a role in their level of susceptibility to HIV/AIDS. This paper draws from interview data of 93 FSWs to construct a multi-layer FSW social network model based on their knowledge, attitude, and practice (KAP). Statistical analyses of the correlation among the three dimensions of KAP as well as their social interactions indicated that FSWs had basic knowledge of HIV/AIDS prevention but demonstrated little enthusiasm in acquiring relevant information. Their knowledge, attitude, and practice were highly positively correlated. Their attitude was more likely to be negatively influenced by their companions, while their practice was more likely to be positively affected. Besides, FSWs exhibited high homophily in KAP with their neighbors. Thus, during HIV/AIDS interventions, FSWs should receive individualized education based on their specific KAP. Considering the high level of homophily among FSWs, their propensity to be positive or negative in their KAP are significantly influenced by their companions. Making full use of peer education and social interaction-based interventions may help prevent and control the spread of HIV/AIDS.