Magnetic modulation on chiroptical activities of nematically assembled carbon dots.

Effectively harnessing the assembly of achiral carbon dots into a chiral manner is a prominent step for applying carbon dots into the area of stereoselective optoelectronics and theranostics. Herein, magnetic-modulated and circularly polarized luminescence (CPL)-active photonic thin films were presented in this article via co-assembly and magnetic-mediation strategy of cellulose nanocrystals, carbon dots and magnetic nanoparticles. The photonic bandgap of the composite films is modulated via interfacial interactions between the building blocks, and more efficiently via external magnetic field which can further enhance the selective reflection of the films with a maximum CPL anisotropic factor as high as -0.92, indicating the optimized condition for achieving CPL signals is basically when the photonic bandgap (PBG) are close to the emission peaks of nanocomposite films, which may essentially facilitate the selective reflection effect and leads to the output of opposite CPL signals. Such strategy would inevitably boost the development of carbon dots based chiral devices and reagents into the realm of chirality-related biological issues and next generation chiral optoelectronics.

Antisense Oligonucleotide STK-002 Increases OPA1 in Retina and Improves Mitochondrial Function in Autosomal Dominant Optic Atrophy Cells.

Autosomal dominant optic atrophy (ADOA) is an inherited optic neuropathy most frequently associated with OPA1 mutations. Most variants result in haploinsufficiency, and patient cells express roughly half of the normal levels of OPA1 protein. OPA1 is a mitochondrial GTPase that is essential for normal mitochondrial function. We identified and characterized STK-002, an antisense oligonucleotide (ASO) designed to prevent the incorporation of a naturally occurring alternatively spliced nonproductive exon in OPA1. STK-002 dose dependently reduced the inclusion of this exon, and increased OPA1 protein in human cells, including ADOA patient-derived fibroblasts. ADOA patient cells manifest reduced mitochondrial respiration, and treatment with STK-002 improved the parameters of mitochondrial respiratory function in these cells. Since STK-002 increases OPA1 through the wild-type allele, we assessed retinal OPA1 in wild-type cynomolgus monkeys and rabbits after intravitreal administration of STK-002 or a rabbit-specific surrogate. Increased OPA1 protein was produced in retinal tissue in both species at 4 weeks after ASO injection and persisted in monkeys at 8 weeks. STK-002 and enhanced OPA1 immunofluorescence were visualized in retinal ganglion cells of cynomolgus monkeys treated with the ASO. Cumulatively, these data support the progression of STK-002 toward the clinic as the first potential disease-modifying treatment for ADOA.

Sensing of Liver-Derived Nicotinamide by Intestinal Group 2 Innate Lymphoid Cells Links Liver Cirrhosis and Ulcerative Colitis Susceptibility.

The correlation between liver disease and the progression of ulcerative colitis (UC) has remained elusive. In this study, it demonstrates that liver injury is intricately linked to the heightened severity of UC in patients, and causes more profound intestinal damage during DSS-induced colitis in mice. Metabolomics analysis of plasma from liver cirrhosis patients shows liver injury compromising nicotinamide supply for NAD+ biosynthesis in the intestine. Subsequent investigation identifies intestinal group 2 innate lymphoid cells (ILC2s) are responsible for liver injury-exacerbated colitis. Reconstitution of ILC2s or the restoration of NAD+ metabolism proves effective in relieving liver injury-aggravated experimental colitis. Mechanistically, the NAD+ salvage pathway regulates gut ILC2s in a cell-intrinsic manner by supporting the generation of succinate, which fuels the electron transport chain to sustaining ILC2s function. This research deepens the understanding of cellular and molecular mechanisms in liver disease-UC interplay, identifying a metabolic target for innovative treatments in liver injury-complicated colitis.

Expression of cytokine and Apoptosis-Associated genes in mice bone Marrow-Derived Macrophages stimulated with Brucella recombinant type IV secretion effectors.

BACKGROUND: Brucellosis is an economically important infectious caused by most commonly by Brucella. Detection of infected animals at the early stage is important for controlling the disease. The diagnostic antigens, usually protein antigens, have attracted much interest. However, the accurate mechanism of immune response is still unknown. The secretory effectors (BPE005, BPE275, and BPE123) of the type IV secretion system (T4SS) were involved in the intracellular circulation process of Brucella and the immune responses of the host. METHODS: Genes encoding three B. abortus effector proteins (BPE005, BPE275, and BPE123) of T4SS were cloned and the recombinant proteins were expressed and purified. The purified recombinant proteins were named rBPE005, rBPE275 and rBPE123. Then, the expressions of Th1- and Th2-related cytokine genes were analyzed in mice bone marrow-derived macrophages (BMDMs) after stimulation with rBPE005, rBPE275, and rBPE123. Furthermore, four apoptosis-associated genes (Caspase-3, Caspase-8, Bax, and Bcl-2) were also detected to explore the damage of the proteins to the cells. RESULTS: Expressions of all Th1- and Th2-related cytokine genes were induced with three proteins, and different cytokine expression patterns induced by each protein depend on the stimulation time and dose of protein. However, expressions of apoptosis-related genes did not change. CONCLUSION: These results showed that the secreted antigens of Brucella induced an immune reaction via the production of Th1- and Th2-type cytokines in BMDMs without exerting any damage on the cells.

RNA-seq reveals the important role of transcriptional regulator DeoR1 in regulating Brucella abortus various pathways.

Brucella spp. is an intracellular bacterium that uses its transcriptional regulator DeoR1 to promote intracellular transport and survival, but the molecular mechanism remains unknown. To analyze the role of DeoR1 in the virulence of B. abortus and the genes regulated by DeoR1, we created a A19ΔdeoR1 mutant of B. abortus A19 (A19). Virulence assay was performed using a murine macrophage cell line (RAW264.7) and mice. We observed that A19ΔdeoR1 mutant is attenuated in RAW264.7 cells and mice. We performed RNA-seq whole transcriptome analysis of A19ΔdeoR1 and A19 from infected RAW264.7 cells. A total of 135 differentially expressed genes were identified, including 100 up-regulated and 35 down-regulated genes. These differentially expressed genes were involved in amino acid synthesis and metabolism, energy production and conversion, stress proteins, chaperonin, hypothetical proteins and protein of unknown function, cell wall/membrane/envelope, intracellular transporting and secretion, and transcriptional regulator. Interestingly, genes involved in the intracellular trafficking and secretion were significantly down-regulated in A19ΔdeoR1. Furthermore, selected RNA-seq results were experimentally confirmed by qRT-PCR. Overall, these results deciphered differential phenomena associated with virulence in A19ΔdeoR1 and A19 from infected RAW264.7 cells, which provided important information for understanding the detailed role of DeoR1 in Brucella pathogenesis. SIGNIFICANCE: Transcriptional regulators are predominant bacterial signal transduction factors. The pathogenicity of Brucella is due to its ability to regulate the expression of virulence related genes. Transcriptional regulators are designed to regulate gene expression and enact an appropriate adaptive physiological response. Here, a total of 135 differentially expressed genes were identified in transcriptional regulator deoR1 mutant.

Three-Dimensional Label-Free Observing of the Self-Assembled Nanoparticles inside a Single Cell at Nanoscale Resolution.

Understanding the intracellular behavior of nanoparticles (NPs) plays a key role in optimizing the self-assembly performance of nanomedicine. However, conducting the 3D, label-free, quantitative observation of self-assembled NPs within intact single cells remains a substantial challenge in complicated intracellular environments. Here, we propose a deep learning combined synchrotron radiation hard X-ray nanotomography approach to visualize the self-assembled ultrasmall iron oxide (USIO) NPs in a single cell. The method allows us to explore comprehensive information on NPs, such as their distribution, morphology, location, and interaction with cell organelles, and provides quantitative analysis of the heterogeneous size and morphologies of USIO NPs under diverse conditions. This label-free, in situ method provides a tool for precise characterization of intracellular self-assembled NPs to improve the evaluation and design of a bioresponsive nanomedicine.

Rapid Synthesis and Microenvironment Optimization of Hierarchical Porous Fe─N─C Catalysts for Enhanced ORR in Microbial Fuel Cells.

Here, an approach to produce a hierarchical porous Fe-N-C@TABOH catalyst with densely accessible high intrinsic active FeNx sites is proposed. The method involves a single-step pyrolysis of Zn/Fe-zeolitic imidazolate framework (Zn/Fe-ZIF-H) with tetrabutylammonium hydroxide (TABOH) micelles, which is obtained by utilizing TABOH as a structural template and electronic mediator at room temperature for a brief duration of 16 min. Notably, the yield of Zn/Fe-ZIF-H is 3.5 times that of Zn/Fe-ZIF-N prepared by conventional method. Results indicate that in addition to expediting synthesis and increasing yield of the Zn/Fe-ZIF-H, the TABOH induces a hierarchical porous structure and fosters the formation of more and higher intrinsic active FeNx moieties in Fex-N-C@TABOH, showing that TABOH is a multifunctional template. Crucially, the increased mesoporosity/external surface area and optimized microenvironment of Fe-N-C@TABOH significantly enhance ORR activity by facilitating the formation of high intrinsic active FeNx sites, increasing accessible FeNx sites, and reducing mass transfer resistance. Through structure tailoring and microenvironment optimization, the resulting Fe-N-C@TABOH exhibits superior ORR performance. DFT calculation further validates that the synergistic effect of these two factors leads to low ORR barrier and optimized *OH adsorption energy. This study underscores the importance of structure and electronic engineering in the development of highly active ORR catalysts.

Defect-engineered dual Z-scheme core-shell MoS2/WO3-x/AgBiS2 for antibiotic and dyes degradation in photo and night catalysis: Mechanism and pathways.

Water pollution caused by antibiotics and synthetic dyes and imminent energy crises due to limited fossil fuel resources are issues of contemporary decades. Herein, we address them by enabling the multifunctionality in dual Z-scheme MoS2/WO3-x/AgBiS2 across photolysis, photo Fenton-like, and night catalysis. Defect, basal, and facet-engineered WO3-x is modified with MoS2 and AgBiS2, which extended its photoresponse from the UV-NIR region, inhibited carrier recombination, and reduced carrier transfer resistance. The electric field rearrangement leads to a flow of electrons from MoS2 and AgBiS2 to WO3-x and intensifies the electron population, which is crucial for night catalysis. When MoS2/WO3-x/AgBiS2 was employed against doxycycline hydrochloride (DOXH), it removed 95.65, 81.11, and 77.92 % of DOXH in 100 min during photo-Fenton (PFR), night-Fenton (NFR), and photocatalytic (PCR) reactions, respectively. It also effectively removed 91.91, 98.17, 99.01, and 98.99 % of rhodamine B (RhB), Congo red (CR), methylene blue (MB), and methylene orange (MO) in Fenton reactions, respectively. ESR analysis consolidates the ROS generation feature of MoS2/WO3-x/AgBiS2 using H2O2 with and without irradiation. This work provides a strategy to eliminate the deficiencies of WO3-x and is conducive to the evolution of applications seeking to combat environmental and energy crises.

Molecular detection of piroplasms in domestic donkeys in Xinjiang, China.

BACKGROUND: Piroplasmosis is a common and prevalent tick-borne disease that affects equids. OBJECTIVES: To determine the infection and molecular characteristics of the piroplasms in donkeys from Xinjiang, northwestern China, we undertook a cross sectional study by collecting representative samples across several counties within the region. METHODS: A total of 344 blood samples were collected from adult domestic donkeys from 13 counties in Xinjiang. PCR was conducted to test for T. equi and B. caballi in the blood samples based on the equine merozoite antigen-1 (Ema-1) gene and the 48 kDa rhoptry protein (BC48) gene, respectively. RESULTS: Sixteen blood samples tested positive for piroplasms and the overall infection rate was 4.7% (16/344). Seven of the 13 counties were positive for piroplasms. Among the 16 piroplasm-positive samples, 15 were singly infected with T. equi with an infection rate of 4.4% (15/344), and coinfection with T. equi and B. caballi was detected in one sample (0.3%, 1/344) from Wushi. Four T. equi sequence genotypes were identified and grouped into different branches of the evolutionary trees. CONCLUSION: These findings suggest that the infection rate of piroplasms is low in domestic donkeys in southern Xinjiang and that T. equi genotypes have a regional distribution.

Insights into the effect of guanylate-binding protein 1 on the survival of Brucella intracellularly.

Brucellosis is a zoonotic disease that affects wild and domestic animals. It is caused by members of the bacterial genus Brucella. Guanylate-binding protein 1 (GBP1) is associated with microbial infections. However, the role of GBP1 during Brucella infection remains unclear. This investigation aimed to identify the association of GBP1 with brucellosis. Results showed that Brucella infection induced GBP1 upregulation in RAW 264.7 murine macrophages. Small interfering GBP1 targeting RNAs were utilized to explore how GBP1 regulates the survival of Brucella intracellularly. Results revealed that GBP1 knockdown promoted Brucella's survival ability, activated Nod-like receptor (NLR) containing a pyrin domain 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammatory corpuscles, and induced pro-inflammatory cytokines IFN-γ and IL-1ß. Furthermore, Brucella stimulated the expression of GBP1 in bone marrow-derived macrophages (BMDMs) and mice. During the inhibition of GBP1 in BMDMs, the intracellular growth of Brucella increased. In comparison, GBP1 downregulation enhanced the accumulation of Brucella-induced reactive oxygen species (ROS) in macrophages. Overall, the data indicate a significant role of GBP1 in regulating brucellosis and suggest the function underlying its suppressive effect on the survival and growth of Brucella intracellularly.

CODENET: A deep learning model for COVID-19 detection.

Conventional COVID-19 testing methods have some flaws: they are expensive and time-consuming. Chest X-ray (CXR) diagnostic approaches can alleviate these flaws to some extent. However, there is no accurate and practical automatic diagnostic framework with good interpretability. The application of artificial intelligence (AI) technology to medical radiography can help to accurately detect the disease, reduce the burden on healthcare organizations, and provide good interpretability. Therefore, this study proposes a new deep neural network (CNN) based on CXR for COVID-19 diagnosis - CodeNet. This method uses contrastive learning to make full use of latent image data to enhance the model's ability to extract features and generalize across different data domains. On the evaluation dataset, the proposed method achieves an accuracy as high as 94.20%, outperforming several other existing methods used for comparison. Ablation studies validate the efficacy of the proposed method, while interpretability analysis shows that the method can effectively guide clinical professionals. This work demonstrates the superior detection performance of a CNN using contrastive learning techniques on CXR images, paving the way for computer vision and artificial intelligence technologies to leverage massive medical data for disease diagnosis.

OVOL2 induces autophagy-mediated epithelial-mesenchymal transition by the ERK1/2 MAPK signaling in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related death worldwide. Epithelial-mesenchymal transition (EMT) plays an important role in malignant tumor progression. Recently, accumulating evidence has shown that autophagy is involved in the regulation of EMT-induced migration. Therefore, the exploration of targets to inhibit EMT by targeting autophagy is important. In this study, we found that OVO-like zinc finger 2 (OVOL2) may be a key target for regulating autophagy-induced EMT. Firstly, we found that OVOL2 expression was dramatically downregulated in LUAD. Low expression of OVOL2 is an indicator of poor prognosis in LUAD. In vitro experiments have shown that downregulation of OVOL2 expression induces EMT, thereby promoting malignant biological behavior, such as proliferation, migration, and invasion of LUAD cells. Interestingly, autophagy is a key step in regulating OVOL2 and inducing EMT. Furthermore, OVOL2 regulates autophagy through the MAPK signaling pathway, ultimately inhibiting the malignant progression of LUAD.

WO3-x nanorods/rGO/AgBiS2 Z-scheme heterojunction with comprehensive spectrum response and enhanced Fenton and photocatalytic activities.

Tetracycline (TC) antibiotics and dyes are the prevalent water contaminants, and their removal from the water through photocatalysis is a plausible approach. However, most semiconductors in their pristine form need to be improved to be exploited in photocatalysis owing to poor photoresponse, intense carrier recombination, and inertness without irradiation. Herein, we demonstrate the modification of defective WO3-x by rGO and AgBiS2 in the form of WO3-x/rGO/AgBiS2 (R2). It exploits the superior conductivity and synergism of rGO to inhibit carrier recombination; thereby, Z-scheme heterojunction with AgBiS2 provides high redox potential. Defects in WO3-x enable electron (e-) storage in R2, which decomposes H2O2 to generate ROS without irradiation. Owing to these essences and broad-spectrum response, it removed 93.72, 82.77, and 84.82% of TC during photo-Fenton (PFR), night-Fenton (NFR), and photocatalytic (PCR) reactions, respectively. Its removal rates reached 94.74, 81.54, and 87.50% against rhodamine B (RhB) during PFR, NFR, and PCR, respectively. It is superior to memory catalysis (MC) and conventional Fenton reactions (CFR) because it can perform without and with irradiation across a broader pH range. So, this work is conducive to designing WO3-x-based catalysts to combat environmental and energy crises.

Developing an ultra-intensified fed-batch cell culture process with greatly improved performance and productivity.

Intensified fed-batch (IFB), a popular cell culture intensification strategy, has been widely used for productivity improvement through high density inoculation followed by fed-batch cultivation. However, such an intensification strategy may counterproductively induce rapidly progressing cell apoptosis and difficult-to-sustain productivity. To improve culture performance, we developed a novel cell culture process intermittent-perfusion fed-batch (IPFB) which incorporates one single or multiple cycles of intermittent perfusion during an IFB process for better sustained cellular and metabolic behaviors and notably improved productivity. Unlike continuous perfusion or other semi-continuous processes such as hybrid perfusion fed-batch with only early-stage perfusion, IPFB applies limited times of intermittent perfusion in the mid-to-late stage of production and still inherits bolus feedings on nonperfusion days as in a fed-batch culture. Compared to IFB, an average titer increase of ~45% was obtained in eight recombinant CHO cell lines studied. Beyond IPFB, ultra-intensified IPFB (UI-IPFB) was designed with a markedly elevated seeding density of 20-80 × 106 cell/mL, achieved through the conventional alternating tangential flow filtration (ATF) perfusion expansion followed with a cell culture concentration step using the same ATF system. With UI-IPFB, up to ~6 folds of traditional fed-batch and ~3 folds of IFB productivity were achieved. Furthermore, the application grounded in these two novel processes showed broad-based feasibility in multiple cell lines and products of interest, and was proven to be effective in cost of goods reduction and readily scalable to a larger scale in existing facilities.

Functional-structural decoupling in visual network is associated with cognitive decline in patients with type 2 diabetes mellitus: evidence from a multimodal MRI analysis.

Type 2 diabetes mellitus (T2DM) and cognitive dysfunction are highly prevalent disorders worldwide. Although visual network (VN) alteration and functional-structural coupling are potential warning factors for mild cognitive impairment (MCI) in T2DM patients, the relationship between the three in T2DM without MCI is unclear. Thirty T2DM patients without MCI and twenty-nine healthy controls (HC) were prospectively enrolled. Visual components (VC) were estimated by independent component analysis (ICA). Degree centrality (DC), amplitude of low frequency fluctuation (ALFF) and fractional anisotropy (FA) were established to reflect functional and structural characteristics in these VCs respectively. Functional-structural coupling coefficients were further evaluated using combined FA and DC or ALFF. Partial correlations were performed among neuroimaging indicators and neuropsychological scores and clinical variables. Three VCs were selected using group ICA. Deteriorated DC, ALFF and DC-FA coefficients in the VC1 were observed in the T2DM group compared with the HC group, while FA and ALFF-FA coefficients in these three VCs showed no significant differences. In the T2DM group, DC in the VC1 positively correlated with 2 dimensions in the California Verbal Learning Test, including Trial 4 and Total trial 1-5. The impaired DC-FA coefficients in the VC1 markedly affected the Total perseverative responses % of the Wisconsin Card Sorting Test. These findings indicate that DC and DC-FA coefficients in VN may be potential imaging biomarkers revealing early cognitive deficits in T2DM.

Commonalities and distinctions between the type 2 diabetes mellitus and Alzheimer's disease: a systematic review and multimodal neuroimaging meta-analysis.

Background: Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are aging related diseases with high incidence. Because of the correlation of incidence rate and some possible mechanisms of comorbidity, the two diseases have been studied in combination by many researchers, and even some scholars call AD type 3 diabetes. But the relationship between the two is still controversial. Methods: This study used seed-based d mapping software to conduct a meta-analysis of the whole brain resting state functional magnetic resonance imaging (rs-fMRI) study, exploring the differences in amplitude low-frequency fluctuation (ALFF) and cerebral blood flow (CBF) between patients (AD or T2DM) and healthy controls (HCs), and searching for neuroimaging evidence that can explain the relationship between the two diseases. Results: The final study included 22 datasets of ALFF and 22 datasets of CBF. The results of T2DM group showed that ALFF increased in both cerebellum and left inferior temporal gyrus regions, but decreased in left middle occipital gyrus, right inferior occipital gyrus, and left anterior central gyrus regions. In the T2DM group, CBF increased in the right supplementary motor area, while decreased in the middle occipital gyrus and inferior parietal gyrus. The results of the AD group showed that the ALFF increased in the right cerebellum, right hippocampus, and right striatum, while decreased in the precuneus gyrus and right superior temporal gyrus. In the AD group, CBF in the anterior precuneus gyrus and inferior parietal gyrus decreased. Multimodal analysis within a disease showed that ALFF and CBF both decreased in the occipital lobe of the T2DM group and in the precuneus and parietal lobe of the AD group. In addition, there was a common decrease of CBF in the right middle occipital gyrus in both groups. Conclusion: Based on neuroimaging evidence, we believe that T2DM and AD are two diseases with their respective characteristics of central nervous activity and cerebral perfusion. The changes in CBF between the two diseases partially overlap, which is consistent with their respective clinical characteristics and also indicates a close relationship between them. Systematic review registration: PROSPERO [CRD42022370014].

Composition and evolutionary characterization of the gut microbiota in pigs.

The intestinal microbiota plays significant role in the physiology and functioning of host organisms. However, there is limited knowledge of the composition and evolution of microbiota-host relationships from wild ancestors to modern domesticated species. In this study, the 16S rRNA gene V3-V4 in the intestinal contents of different pig breeds was analyzed and was compared using high-throughput sequencing. This identified 18 323 amplicon sequence variants, of which the Firmicutes and Actinobacteria phyla and Bifidobacterium and Allobaculum genera were most prevalent in wild pigs (WP). In contrast, Proteobacteria and Firmicutes predominated in Chinese Shanxi Black pigs (CSB), while Firmicutes were the most prevalent phylum in Large White pigs (LW) and Iberian pigs (IB), followed by Bacteroidetes in IB and Proteobacteria in LW. At the genus level, Shigella and Lactobacillus were most prevalent in CSB and LW, while Actinobacillus and Sarcina predominated in IB. Differential gene expression together with phylogenetic and functional analyses indicated significant differences in the relative abundance of microbial taxa between different pig breeds. Although many microbial taxa were common to both wild and domestic pigs, significant diversification was observed in bacterial genes that potentially influence host phenotypic traits. Overall, these findings suggested that both the composition and functions of the microbiota were closely associated with domestication and the evolutionary changes in the host. The members of the microbial communities were vertically transmitted in pigs, with evidence of co-evolution of both the hosts and their intestinal microbial communities. These results enhance our understanding and appreciation of the complex interactions between intestinal microbes and hosts and highlight the importance of applying this knowledge in agricultural and microbiological research.

Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides.

Antimicrobial peptides (AMPs) are important mediators of intestinal immune surveillance. However, the regional heterogeneity of AMPs and its regulatory mechanisms remain obscure. Here, we clarified the regional heterogeneity of intestinal AMPs at the single-cell level, and revealed a cross-lineages AMP regulation mechanism that bile acid dependent transcription factors (BATFs), NR1H4, NR1H3 and VDR, regulate AMPs through a ligand-independent manner. Bile acids regulate AMPs by perturbing cell differentiation rather than activating BATFs signaling. Chromatin accessibility determines the potential of BATFs to regulate AMPs at the pre-transcriptional level, thus shaping the regional heterogeneity of AMPs. The BATFs-AMPs axis also participates in the establishment of intestinal antimicrobial barriers of fetuses and the defects of antibacterial ability during Crohn's disease. Overall, BATFs and chromatin accessibility play essential roles in shaping the regional heterogeneity of AMPs at pre- and postnatal stages, as well as in maintenance of antimicrobial immunity during homeostasis and disease.