Effects of the Interaction between Rumen Microbiota Density-VFAs-Hepatic Gluconeogenesis on the Adaptability of Tibetan Sheep to Plateau.

During the adaptive evolution of animals, the host and its gut microbiota co-adapt to different elevations. Currently, there are few reports on the rumen microbiota-hepato-intestinal axis of Tibetan sheep at different altitudes. Therefore, the purpose of this study was to explore the regulatory effect of rumen microorganism-volatile fatty acids (VFAs)-VFAs transporter gene interactions on the key enzymes and genes related to gluconeogenesis in Tibetan sheep. The rumen fermentation parameters, rumen microbial densities, liver gluconeogenesis activity and related genes were determined and analyzed using gas chromatography, RT-qPCR and other research methods. Correlation analysis revealed a reciprocal relationship among rumen microflora-VFAs-hepatic gluconeogenesis in Tibetan sheep at different altitudes. Among the microbiota, Ruminococcus flavefaciens (R. flavefaciens), Ruminococcus albus (R. albus), Fibrobactersuccinogenes and Ruminobacter amylophilus (R. amylophilus) were significantly correlated with propionic acid (p < 0.05), while propionic acid was significantly correlated with the transport genes monocarboxylate transporter 4 (MCT4) and anion exchanger 2 (AE2) (p < 0.05). Propionic acid was significantly correlated with key enzymes such as pyruvate carboxylase, phosphoenolpyruvic acid carboxylase and glucose (Glu) in the gluconeogenesis pathway (p < 0.05). Additionally, the expressions of these genes were significantly correlated with those of the related genes, namely, forkhead box protein O1 (FOXO1) and mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2) (p < 0.05). The results showed that rumen microbiota densities differed at different altitudes, and the metabolically produced VFA contents differed, which led to adaptive changes in the key enzyme activities of gluconeogenesis and the expressions of related genes.

Facet-Dependent Passivation for Efficient Perovskite Solar Cells.

Understanding the interplay between the surface structure and the passivation materials and their effects associated with surface structure modification is of fundamental importance; however, it remains an unsolved problem in the perovskite passivation field. Here, we report a surface passivation principle for efficient perovskite solar cells via a facet-dependent passivation phenomenon. The passivation process selectively occurs on facets, which is observed with various post-treatment materials with different functionality, and the atomic arrangements of the facets determine the alignments of the passivation layers. The profound understanding of facet-dependent passivation leads to the finding of 2-amidinopyridine hydroiodide as the material for a uniform and effective passivation on both (100) and (111) facets. Consequently, we achieved perovskite solar cells with an efficiency of 25.10% and enhanced stability. The concept of facet-dependent passivation can provide an important clue on unidentified passivation principles for perovskite materials and a novel means to enhance the performance and stability of perovskite-based devices.

Suppressing ion migration in metal halide perovskite via interstitial doping with a trace amount of multivalent cations.

Cations with suitable sizes to occupy an interstitial site of perovskite crystals have been widely used to inhibit ion migration and promote the performance and stability of perovskite optoelectronics. However, such interstitial doping inevitably leads to lattice microstrain that impairs the long-range ordering and stability of the crystals, causing a sacrificial trade-off. Here, we unravel the evident influence of the valence states of the interstitial cations on their efficacy to suppress the ion migration. Incorporation of a trivalent neodymium cation (Nd3+) effectively mitigates the ion migration in the perovskite lattice with a reduced dosage (0.08%) compared to a widely used monovalent cation dopant (Na+, 0.45%). The photovoltaic performances and operational stability of the prototypical perovskite solar cells are enhanced with a trace amount of Nd3+ doping while minimizing the sacrificial trade-off.

2,4,6-TCP migrates and transforms in different cultivated soil in China: Kinetic analysis and mechanistic modeling.

Organochlorine pesticides are widely used in agriculture, wood preservation, pulp bleaching and other fields, which increased the pollution risk of cultivated land. In this study, a typical organochlorine pesticides-2,4,6-TCP was conducted as the target pollutants to investigated the migration and transformation characteristics in different cultivated soils in China. The results indicated that the adsorption of 2,4,6-TCP in soil samples was in order: black soil＞laterite＞fluvo-aquic soil, and the maximum adsorption was 71.0870, 27.0575 and 6.1292 mg/kg, respectively. The dispersion coefficient of black soil, laterite and fluvo-aquic soil was 0.0329, 0.0501 and 0.0149, and the hysteretic factor R was 5.381, 1.455 and 2.238, respectively, indicating that the migration ability of 2,4,6-TCP in different cultivated soils samples was in order: black soil＞laterite＞fluvo-aquic soil. The fitting results of one-dimensional migration model indicated that the model well reflected the migration and transformation of 2,4,6-TCP in different cultivated soil samples. Meanwhile, the Two-dimensional migration model fitting results indicated that the maximum concentration of 2,4,6-TCP of different cultivated soil samples were found along the longitudinal flow direction, reaching 40% of the initial pollution concentration at 15 m, corresponding to the center of the pollutant plume.

Ecological time lags in biodiversity response to habitat changes.

The decline of biodiversity can occur with a substantial delay following habitat loss, degradation, and other environmental changes, such as global warming. Considerable time lags may be involved in these responses. However, such time lags typically pose a significant but often unrecognized challenge for biodiversity conservation across a wide range of taxa and ecosystems. Here, we synthesize the current knowledge, categories, manifestations under different scenarios and impacts of ecological time lags. Our work reveals that studies on ecosystem structure lags are far more than ecosystem process and function lags. Due to the presence of these time-lag effects, the 'window phase' typically exists, which is widely recognized as 'relaxation time', providing a particular opportunity for biodiversity conservation. The manifestations of time lags vary under different scenarios. In addition, the different mechanisms that can result in ecological time lags are hierarchically nested, in which mechanisms at the population and metapopulation level have routinely been suggested as explanations for ecological time lags. It generally takes longer time to reach equilibrium at the metapopulation level than it takes for effects to be fully expressed at the level of individuals. Finally, we propose corresponding implications for biodiversity conservation and management. Our research will provide priorities for science and management on how to address the impact of ecological time lags to mitigate future attrition of biodiversity.

Nanoscale vacuum channel transistor with in-plane collection structure.

High quality nanoscale vacuum channel transistors (NVCTs) enable carriers to transport ballistically through the vacuum nanogap, achieving high speed and frequency characteristic which are essential for on-chip vacuum electronic devices. However, the studies to date have been largely confined to explore the common electrical performance, while the fast response characteristic of NVCTs remains a challenge. We report the fabrication of metal-based NVCT, with sub-100 nm vacuum channel and specific designed in-plane collection structure which can enhance the emission or collection efficiency of the electrons simultaneously. Importantly, the demonstration of a rise/fall time of less than 100 ns is achieved, which is compatible with those high-quality solid-state transistors based on low-dimensional materials. Moreover, the device can also retain excellent electrical performance, exhibiting a high drive current (>10 µA), low work voltage (<10 V) and high on/off current ratio (>104). The verification of fast temporal response of NVCT makes a significant step towards on-chip vacuum electronics with high speed and integration.

The influence of coronavirus disease 2019 on emergency department visits in Nanjing, China: A multicentre cross-sectional study.

INTRODUCTION: Influenza has been linked to the crowding in emergency departments (ED) across the world. The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on China EDs has been quite different from those during past influenza outbreaks. Our objective was to determine if COVID-19 changed ED visit disease severity during the pandemic. METHODS: This was a retrospective cross sectional study conducted in Nanjing, China. We captured ED visit data from 28 hospitals. We then compared visit numbers from October 2019 to February 2020 for a month-to-month analysis and every February from 2017 to 2020 for a year-to-year analysis. Inter-group chi-square test and time series trend tests were performed to compare visit numbers. The primary outcome was the proportion of severe disease visits in the EDs. RESULTS: Through February 29 th 2020, there were 93 laboratory-confirmed COVID-19 patients in Nanjing, of which 40 cases (43.01%) were first seen in the ED. The total number of ED visits in Nanjing in February 2020, were dramatically decreased (n = 99,949) in compared to January 2020 (n = 313,125) and February 2019 (n = 262,503). Except for poisoning, the severe diseases in EDs all decreased in absolute number, but increased in proportion both in year-to-year and month-to-month analyses. This increase in proportional ED disease severity was greater in higher-level referral hospitals when compared year by year. CONCLUSION: The COVID-19 outbreak has been associated with decreases in ED visits in Nanjing, China, but increases in the proportion of severe ED visits.

iTRAQ-based proteomic profiling of Vibrio parahaemolyticus under various culture conditions.

BACKGROUND: Vibrio parahaemolyticus is a common pathogen infecting humans and marine animals; this pathogen has become a major concern of marine food products and trade. In this study, V. parahaemolyticus isolated from sewage was exposed to different culture conditions and analyzed by isobaric tag for relative and absolute quantitation (iTRAQ) based reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. Our goal is to gain further insights into the proteomics of V. parahaemolyticus, particularly differentially expressed proteins closely correlated with growth conditions and pathogenicity associated proteins. RESULTS: In this study, a total of 2,717 proteins including numerous membrane proteins were significantly identified, and 616 proteins displayed significant differential expression under different conditions. Of them, 12 proteins mainly participating in metabolism showed the most elastic expression differentiation between different culture conditions. Some membrane proteins such as type I secretion outer membrane protein, TolC, lipoprotein, efflux system proteins iron-regulated protein A and putaive Fe-regulated protein B, ferric siderophore receptor homolog and several V. parahaemolyticus virulence-associated proteins were differentially regulated under different conditions. Some differentially regulated proteins were analyzed and confirmed at gene expression level by quantitative real time polymerase chain reaction (qRT-PCR). CONCLUSIONS: Proteomics analysis results revealed the characteristics of V. parahaemolyticus proteome expression, provided some promising biomarkers related with growth conditions, the results likely advance insights into the mechanism involved in the response of V. parahaemolyticus to different conditions. Some virulence-associated proteins were discovered to be differentially expressed under different conditions.

Effective hyper-connectivity network construction and learning: Application to major depressive disorder identification.

Functional connectivity (FC) derived from resting-state fMRI (rs-fMRI) is a primary approach for identifying brain diseases, but it is limited to capturing the pairwise correlation between regions-of-interest (ROIs) in the brain. Thus, hyper-connectivity which describes the higher-order relationship among multiple ROIs is receiving increasing attention. However, most hyper-connectivity methods overlook the directionality of connections. The direction of information flow constitutes a pivotal factor in shaping brain activity and cognitive processes. Neglecting this directional aspect can lead to an incomplete understanding of high-order interactions within the brain. To this end, we propose a novel effective hyper-connectivity (EHC) network that integrates direction detection and hyper-connectivity modeling. It characterizes the high-order directional information flow among multiple ROIs, providing a more comprehensive understanding of brain activity. Then, we develop a directed hypergraph convolutional network (DHGCN) to acquire deep representations from EHC network and functional indicators of ROIs. In contrast to conventional hypergraph convolutional networks designed for undirected hypergraphs, DHGCN is specifically tailored to handle directed hypergraph data structures. Moreover, unlike existing methods that primarily focus on fMRI time series, our proposed DHGCN model also incorporates multiple functional indicators, providing a robust framework for feature learning. Finally, deep representations generated via DHGCN, combined with demographic factors, are used for major depressive disorder (MDD) identification. Experimental results demonstrate that the proposed framework outperforms both FC and undirected hyper-connectivity models, as well as surpassing other state-of-the-art methods. The identification of EHC abnormalities through our framework can enhance the analysis of brain function in individuals with MDD.

Impact of non-Saccharomyces yeasts derived from traditional fermented foods on beer aroma: Analysis based on HS-SPME-GC/MS combined with chemometrics.

In recent years, numerous studies have demonstrated the significant potential of non-Saccharomyces yeasts in aroma generation during fermentation. In this study, 134 strains of yeast were isolated from traditional fermented foods. Subsequently, through primary and tertiary screening, 28 strains of aroma-producing non-Saccharomyces yeast were selected for beer brewing. Headspace-solid phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) and chemometrics were employed to analyze the volatile flavor substances in beer samples fermented using these strains. Chemometric analysis revealed that distinct species of non-Saccharomyces yeast had a unique influence on beer aroma, with strains from the same genus producing more similar flavor profiles. Accordingly, 2,6-nonadienal, 1-pentanol, phenyl ethanol, isoamyl acetate, ethyl caprate, butyl butyrate, ethyl propionate, furfuryl alcohol, phenethyl acetate, ethyl butyrate, ethyl laurate, acetic acid, and 3-methyl-4 heptanone were identified as the key aroma compounds for distinguishing among different non-Saccharomyces yeast species. This work provides useful insights into the aroma-producing characteristics of different non-Saccharomyces yeasts to reference the targeted improvement of beer aroma.

Development and Validation of an Internet-Based Remote Perimeter (Perimouse).

Purpose: We sought to validate the feasibility of Perimouse, an internet-based remote perimeter that allows for natural fixation and can be performed on most computers via a web page. Methods: In this cross-sectional study, Perimouse evaluated the visual field of 45 healthy people and 27 patients with primary open-angle glaucoma on a laptop. Participants used a mouse cursor to locate new dots on the screen that were determined by preset saccade vectors. A "click and confirm" strategy was used to eliminate the unwanted visual search. Dot brightness was either fixed at 12 dB in the suprathreshold program (screening program) or variable in the threshold program. We compared Perimouse outcomes with the Humphrey Field Analyzer (HFA) 24-2 Swedish Interactive Testing Algorithm standard program. Results: In the screening program, Perimouse showed moderate to high concordance with HFA. The intraclass coefficient ranged from 0.58 to 0.86 in different areas of Garway-Heath mapping. In the threshold program, normal subjects had threshold ranging from 19 to 16 dB, presenting sensitivity changes according to the "hill of vision". The test-retest difference was 0.09 dB. Habitual spectacle correction and environmental luminance (2-337 lux) had little impact on the central or peripheral threshold (P > 0.05). The correlation between Perimouse and HFA threshold sensitivity was strong (R = 0.950), although Perimouse mean defect was 4.40 dB higher than the HFA mean defect. Conclusions: Perimouse is a reliable visual field test that correlates strongly with HFA. It shows potential for population screening and monitoring visual field defects. Translational Relevance: Perimouse assesses the visual field using saccade vectors without eye trackers, enhancing its accessibility via a web page.

Supplementation with Astragalus Root Powder Promotes Rumen Microbiota Density and Metabolome Interactions in Lambs.

The gut microbiota is highly symbiotic with the host, and the microbiota and its metabolites are essential for regulating host health and physiological functions. Astragalus, as a feed additive, can improve animal immunity. However, the effects of Astragalus root powder on the rumen microbiota and their metabolites in lambs are not apparent. In this study, thirty healthy Hu sheep lambs with similar body weights (17.42 ± 2.02 kg) were randomly selected for the feeding experiment. Lambs were fed diets supplemented with 0.3% Astragalus root powder, and the rumen microbiota density and metabolome were measured to determine the effects of Astragalus on the health of lambs in the rumen. The results showed that the relative abundance of Butyrivibrio fibrisolvens (Bf), Ruminococcus flavefaciens (Rf), Succiniclasticum (Su), and Prevotella (Pr) in the rumen was increased in the Astragalus group (p < 0.01), and metabolic profiling showed that the metabolites, such as L-lyrosine and L-leucine, were upregulated in the Astragalus group (p < 0.01). KEGG functional annotation revealed that upregulated metabolites were mainly enriched in the pathways of amino acid metabolism, lipid metabolism, fatty acid biosynthesis, and bile secretion in the Astragalus group, and downregulated metabolites were enriched in the pathways of methane metabolism and other pathways. Correlation analysis revealed that butyric acid was positively correlated with Roseburia and Blautia (p < 0.05) and negatively correlated with Desulfovibrio (p < 0.05). Thus, by analyzing the interactions of Astragalus root powder with the density of rumen microorganisms and their metabolites in lambs, it was shown that Astragalus root powder could improve the structure of rumen microbiota and their metabolites and then participate in the regulation of amino acid metabolism, lipid metabolism, immune metabolism, and other pathways to improve the efficiency of energy absorption of the lambs.

Multi-omics revealed rumen microbiota metabolism and host immune regulation in Tibetan sheep of different ages.

The rumen microbiota and metabolites play an important role in energy metabolism and immune regulation of the host. However, the regulatory mechanism of rumen microbiota and metabolite interactions with host on Tibetan sheep's plateau adaptability is still unclear. We analyzed the ruminal microbiome and metabolome, host transcriptome and serum metabolome characteristics of Tibetan sheep at different ages. Biomarkers Butyrivibrio, Lachnospiraceae_XPB1014_group, Prevotella, and Rikenellaceae_RC9_gut_group were found in 4 months, 1.5 years, 3.5 years, and 6 years Tibetan sheep, respectively. The rumen microbial metabolites were mainly enriched in galactose metabolism, unsaturated fatty acid biosynthesis and fatty acid degradation pathways, and had significant correlation with microbiota. These metabolites further interact with mRNA, and are co-enriched in arginine and proline metabolism, metabolism of xenobiotics by cytochrome P450, propanoate metabolism, starch and sucrose metabolism, gap junction pathway. Meanwhile, serum metabolites also have a similar function, such as chemical carcinogenesis - reactive oxygen species, limonene and pinene degradation, and cutin, suberine and wax biosynthesis, thus participating in the regulation of the body's immune and energy-related metabolic processes. This study systematically revealed that rumen microbiota, metabolites, mRNA and serum metabolites of Tibetan sheep were involved in the regulation of fermentation metabolic function and immune level of Tibetan sheep at different ages, which provided a new perspective for plateau adaptability research of Tibetan sheep at different ages.

Construction of biochar-based organohalide-respiring bacterial agent for remediation of 2,4,6-trichlorophenol contaminated soil.

Construction of an efficient bio-reductive dechlorination system remains challenging due to the narrow ecological niche and low-growth rate of organohalide-respiring bacteria during field remediation. In this study, a biochar-based organohalide-respiring bacterial agent was obtained, and its performance and effects on indigenous microbial composition, diversity, and inter-relationship in soil were investigated. A well-performing material, Triton X-100 modified biochar (BC600-TX100), was found to have the superior average pore size, specific surface area and hydrophicity, compared to other materials. Interestingly, Pseudomonas aeruginosa CP-1, which is capable of 2,4,6-TCP dechlorination, showed a 348 times higher colonization cell number on BC600-TX100 than that of BC600 after 7 d. Meanwhile, the dechlorination rate in soil showed the highest (0.732 d-1) in the BC600-TX100 bacterial agent than in the other agents. The long-term performance of the BC600-TX100 OHRB agent was also verified, with a stable dechlorination activity over six cycles. Soil microbial community analysis found the addition of the BC600-TX100 OHRB agent significantly increased the relative abundance of genus Pseudomonas from 1.53 % to 11.2 %, and Pseudomonas formed a close interaction relationship with indigenous microorganisms, creating a micro-ecological environment conducive to reductive dechlorination. This study provides a feasible bacterial agent for the in-situ bioremediation of soil contaminated organohalides. ENVIRONMENTAL IMPLICATION: Halogenated organic compounds are a type of toxic, refractory, and bio-accumulative persistent compounds widely existed in environment, widely detected in the air, water, and soil. In this study, we provide a feasible bacterial agent for the in-situ bioremediation of soil contaminated halogenated organic compounds. The application of biochar provides new insights for "Turning waste into treasure", which meets with the concept of green chemistry.

Study of the Interactions between Muscle Fatty Acid Composition, Meat Quality-Related Genes and the Ileum Microbiota in Tibetan Sheep at Different Ages.

The intestinal microbiota of ruminants is an important factor affecting animal production and health. Research on the association mechanism between the intestinal microbiota and meat quality of ruminants will play a positive role in understanding the formation mechanism of meat quality in ruminants and improving production efficiency. In this study, the fatty acid composition and content, expression of related genes, and structural characteristics of the ileum microbiota of ewes of Tibetan sheep at different ages (4 months, 1.5 years, 3.5 years, and 6 years) were detected and analyzed. The results revealed significant differences in fatty acid composition and content in the muscle of Tibetan sheep at different ages (p < 0.05); in addition, the content of MUFAs in the longissimus dorsi muscle and leg muscle was higher. Similarly, the expressions of muscle-related genes differed among the different age groups, and the expression of the LPL, SCD, and FABP4 genes was higher in the 1.5-year-old group. The ileum microbiota diversity was higher in the 1.5-year-old group, the Romboutsia abundance ratio was significantly higher in the 1.5-year-old group (p < 0.05), and there was a significant positive correlation with oleic acid (C18:1n9c) (p < 0.05). In conclusion, the content of beneficial fatty acids in the longissimus dorsi muscle and leg muscle of Tibetan sheep was higher at 1.5 years of age, and the best slaughter age was 1.5 years. This study provides a reference for in-depth research on the mechanism of the influence of the gut microbiota on meat quality and related regulation.

Continuous 24-hour intraocular pressure monitoring in normal Chinese adults using a novel contact lens sensor system.

AIMS: To investigate the physiological nyctohemeral intraocular pressure (IOP) rhythms of normal Chinese adults using a novel contact lens sensor system (CLS) that can output IOP in millimetres of mercury (mm Hg) continuously. METHODS: Fifty-nine eyes of 59 normal Chinese adults completed 24-hour IOP monitoring using the novel CLS. A descriptive analysis was conducted on the 24-hour IOP mean, peak and acrophase, trough and bathyphase, fluctuation, and mean amplitude of intraocular pressure excursion (MAPE). The continuous data were analysed at several periods (diurnal period, 08:00-20:00 hours; nocturnal period, 22:00-06:00 hours; sleep time, 0:00-06:00 hours), and compared between right and left eyes, males and females, and different age ranges (<30, and ≥30), respectively. RESULTS: Normal adults had a lower peak, higher trough, smaller fluctuation and smaller MAPE (p<0.05 for all comparisons) but non-significantly different mean (p=0.695) in the nocturnal period or sleep time compared with the diurnal period. The 24-hour IOP peak and trough showed the frequency of occurrence ranging from 1.69% to 15.25% at an interval of 2 hours. No IOP parameter showed significant difference between right and left eyes (p>0.1 for all comparisons). The male group had larger 24-hour and diurnal IOP fluctuation and MAPE (p<0.05 for all comparisons). Subjects aged 30 or over had higher 24-hour and diurnal mean, higher peak, and larger MAPE (p<0.05 for all comparisons). CONCLUSION: Continuous 24-hour IOP output from the CLS in normal Chinese was stable with a comparable mean level between day and night, as well as scattered acrophase and bathyphase. The 24-hour IOP mean increased with age, and IOP variations were positively correlated to age and male sex.

IARS2 mutations lead to Leigh syndrome with a combined oxidative phosphorylation deficiency.

BACKGROUND: Leigh syndrome (LS) is a common mitochondrial disease caused by mutations in both mitochondrial and nuclear genes. Isoleucyl-tRNA synthetase 2 (IARS2) encodes mitochondrial isoleucine-tRNA synthetase, and variants in IARS2 have been reported to cause LS. However, the pathogenic mechanism of IARS2 variants is still unclear. METHODS: Two unrelated patients, a 4-year-old boy and a 5-year-old boy diagnosed with LS, were recruited, and detailed clinical data were collected. The DNA of the patients and their parents was isolated from the peripheral blood for the identification of pathogenic variants using next-generation sequencing and Sanger sequencing. The ClustalW program, allele frequency analysis databases (gnomAD and ExAc), and pathogenicity prediction databases (Clinvar, Mutation Taster and PolyPhen2) were used to predict the conservation and pathogenicity of the variants. The gene expression level, oxygen consumption rate (OCR), respiratory chain complex activity, cellular adenosine triphosphate (ATP) production, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (ROS) levels were measured in patient-derived lymphocytes and IARS2-knockdown HEK293T cells to evaluate the pathogenicity of the variants. RESULTS: We reported 2 unrelated Chinese patients manifested with LS who carried biallelic IARS2 variants (c.1_390del and c.2450G > A from a 4-year-old boy, and c.2090G > A and c.2122G > A from a 5-year-old boy), of which c.1_390del and c.2090G > A were novel. Functional studies revealed that the patient-derived lymphocytes carrying c.1_390del and c.2450G > A variants exhibited impaired mitochondrial function due to severe mitochondrial complexes I and III deficiencies, which was also found in IARS2-knockdown HEK293T cells. The compensatory experiments in vitro cell models confirmed the pathogenicity of IARS2 variants since re-expression of wild-type IARS2 rather than mutant IARS2 could rescue complexes I and III deficiency, oxygen consumption, and cellular ATP content in IARS2 knockdown cells. CONCLUSION: Our results not only expand the gene mutation spectrum of LS, but also reveal for the first time the pathogenic mechanism of IARS2 variants due to a combined deficiency of mitochondrial complexes I and III, which is helpful for the clinical diagnosis of IARS2 mutation-related diseases.

LL-37 and bisphosphonate co-delivery 3D-scaffold with antimicrobial and antiresorptive activities for bone regeneration.

This study introduces a novel 3D scaffold for bone regeneration, composed of silk fibroin, chitosan, nano-hydroxyapatite, LL-37 antimicrobial peptide, and pamidronate. The scaffold addresses a critical need in bone tissue engineering by simultaneously combating bone infections and promoting bone growth. LL-37 was incorporated for its broad-spectrum antimicrobial properties, while pamidronate was included to inhibit bone resorption. The scaffold's porous structure, essential for cell infiltration and nutrient diffusion, was achieved through a freeze-drying process. In vitro assessments using SEM and FTIR confirmed the scaffold's morphology and chemical integrity. Antimicrobial efficacy was tested against pathogens of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). In vivo studies in a murine model of infectious bone defect revealed the scaffold's effectiveness in reducing inflammation and bacterial load, and promoting bone regeneration. RNA sequencing of treated specimens provided insights into the molecular mechanisms underlying these observations, revealing significant gene expression changes related to bone healing and immune response modulation. The results indicate that the scaffold effectively inhibits bacterial growth and supports bone cell functions, making it a promising candidate for treating infectious bone defects. Future studies should focus on optimizing the release of therapeutic agents and evaluating the scaffold's clinical potential.

Differentiated environmental taxes and high-quality economic development in China: theory and evidence.

Environmental tax policy plays an important role in promoting economic efficiency, but it is unclear whether the taxation is well-designed and effective. The differentiated environmental tax and fee policy in China has come a long way in the past 20 years, along with the aim of high-quality economic development that focuses on the harmony of environment and productivity, so it is necessary to evaluate the effectiveness of the differentiated environmental tax and fee policy. This paper constructs a pollution and environmental tax model based on the new economic geography framework to simulate the effect of environmental tax and technological innovation in the eastern and western region on pollution, output, and productivity. Using China's provincial panel data from 2005 to 2020 with difference-in-difference method, empirical evidence shows that differentiated environmental tax and fee adjustments generally boost industrial high-quality development by the industrial sulfur dioxide emission deduction and green total factor productivity improvement. When the adjustment is more differentiated between treatment and control, the effect is greater and more significant. Additionally, high environmental tax standard in high SO2 emission provinces significantly contributes to high-quality development. Progressive adjustments in 2007, 2014, and 2018 lead to heterogeneous policy effect. Technological innovation plays a mediating effect between differentiated environmental tax and high-quality economic development. The results above provide theoretical analysis and empirical study of China's differentiated environmental taxes and high-quality economic development for policy making.

Wetting-State-Induced Turning of Water Droplet Moving Direction on the Surface.

The spontaneous directional movement of water droplets on a wedge-shaped groove has gained extensive attention due to the advantage of not requiring energy input and its potential wide applications. However, manipulating the direction of movement of water droplets on a wedge-shaped groove has been not fully achieved, and the fundamental understanding of its underlying mechanism remains unclear. Here, molecular dynamics simulations and theoretical analyses are combined to reveal the mechanism of movement in opposite directions of a water droplet at the same position on the wedge-shaped groove interface. It is shown that the moving direction of the water droplet is related to its wetting state on the surface, i.e., the Wenzel and the Cassie states. A water droplet initially in the Wenzel and Cassie states will move toward the diverging and the converging ends, respectively. This phenomenon is attributed to the opposite roles played by the groove substrate and the upper layers in the two wetting states. Moreover, it is found that the water droplet is likely to move faster on a surface with a higher groove, larger opening angle and stronger hydrophobicity. These findings are expected to be of benefit for fully understanding droplet movement and shedding light on the regulation of the direction of movement of the droplets on the groove surface.