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Purpose: Tumor-associated macrophages (TAMs) play a crucial role in shaping various tumor microenvironments. However, their recruitment in Wilms tumor (WT), the predominant malignant renal tumor in children, has been inadequately explored. This retrospective cohort study involved the analysis of 148 WT samples to investigate the recruitment and polarization typing of TAMs in WT tissues. Methods: WT tissues underwent Western blotting (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence (IF) to measure the expression of TAM markers CD68, CD86, and CD163. Statistically analyze the relationship between TAM recruitment levels and patient clinical characteristics, and use Kaplan-Meier curves and the log-rank test to evaluate the association between TAM levels and survival outcomes. Results: The findings indicated a positive correlation between the recruitment levels of total macrophages (Mtotal) and M2 tumor-associated macrophages (M2 TAM) in both chemotherapy and non-chemotherapy groups with the clinical stage. Elevated recruitment of Mtotal and M2 TAM in tumor tissues was linked to a poorer prognosis. Notably, patients with persistently higher recruitment of M2 TAM following preoperative chemotherapy exhibited the worst prognosis. Conclusions: The recruitment and polarization typing of TAM exhibit significant differences in WT patients with various stages and prognosis outcomes, suggesting a potential avenue for future diagnosis and treatment of WT. [ABSTRACT FROM AUTHOR]

Nonconventional luminescent materials (NLMs) are a type of organic luminescent materials that does not contain aromatic units. Due to the simplicity of the synthesis process, mild reaction conditions, good hydrophilicity and biological compatibility, NLMs have attracted much attention. Nevertheless, numerous reports indicate that NLMs can only effectively luminesce at high concentrations and in solid state, which limits their applicability in the field of cell imaging. This study addresses this limitation by designing and synthesizing oligomers P1, P2 and P3 using ethylene glycol diglycidyl ether and amine compounds containing ethylene groups. These oligomers exhibit remarkable luminescence efficiency reaching as high as 9.2% in dilute solutions (0.1 mg/mL), making them among the best NLMs in this category. Furthermore, the synthesized oligomers exhibit excitation wavelength-dependent and concentration-dependent luminescence intensity, fluorescence response to temperature and pH changes, as well as the ability to identify Fe3+, Cu2+ and Mo5+ in dilute solutions. These characteristics render them potentially useful in the for cell imaging. [ABSTRACT FROM AUTHOR]

Purpose: Wilms' tumor (WT), also known as nephroblastoma, is the predominant form of primary malignant renal cancer. The unfavorable prognoses linked to anaplastic nephroblastoma and recurrent nephroblastoma emphasize the crucial requirement for the exploration of innovative treatment modalities for WT. Methods: Our study conducted one-way Cox regression and Kaplan-Meier analyses using TARGET-WT nephroblastoma data to identify differentially expressed genes in nephroblastoma and evaluate their prognostic relevance. Utilizing the Connectivity Map database, ZSTK474 emerged as a viable therapeutic option for WT. The effect of ZSTK474 on WT and related underlying mechanisms were further investigated through in vitro and in vivo investigations. Results: The in vivo experiment results indicated that ZSTK474 effectively inhibited subcutaneous tumor growth in WT mice. CCK-8 assays revealed two nephroblastoma cell lines exhibited half-inhibitory concentrations of 2μM and 2.51μM for ZSTK474, respectively. ZSTK474 was shown to inhibit the migration and invasion capabilities of WT cells in both Transwell and wound healing assays. Flow cytometry apoptosis and TUNEL assays demonstrated that ZSTK474 induced apoptosis in WT cells. Cell cycle analysis revealed that ZSTK474 led to the induction of G0/G1 phase arrest. Sequencing of ZSTK474-treated WiT49 cells suggested that the impact of ZSTK474 on WT might be mediated by the PI3K/Akt pathway, specifically by inhibiting PIK3R3. Knock-down of PIK3R3 confirmed that ZSTK474 downregulated PIK3R3, reducing Akt phosphorylation, cyclin D and CDK4 levels and elevating P21 expression in nephroblastoma cells. However, current research has limitations, including a lack of understanding of the long-term effects and potential resistance mechanisms of new therapies. Conclusion: This research provides insight into the potential of ZSTK474 and other PI3K inhibitors for treating nephroblastoma. [ABSTRACT FROM AUTHOR]

Organic phosphorescent materials are excellent candidates for use in tumor imaging. However, a systematic comparison of the effects of the intensity, lifetime, and wavelength of phosphorescent emissions on bioimaging performance has not yet been undertaken. In addition, there have been few reports on organic phosphorescent materials that specifically distinguish tumors from normal tissues. This study addresses these gaps and reveals that longer lifetimes effectively increase the signal intensity, whereas longer wavelengths enhance the penetration depth. Conversely, a strong emission intensity with a short lifetime does not necessarily yield robust imaging signals. Building upon these findings, an organo‐phosphorescent material with a lifetime of 0.94 s was designed for tumor imaging. Remarkably, the phosphorescent signals of various organic nanoparticles are nearly extinguished in blood‐rich organs because of the quenching effect of iron ions. Moreover, for the first time, we demonstrated that iron ions universally quench the phosphorescence of organic room‐temperature phosphorescent materials, which is an inherent property of such substances. Leveraging this property, both the normal liver and hepatitis tissues exhibit negligible phosphorescent signals, whereas liver tumors display intense phosphorescence. Therefore, phosphorescent materials, unlike chemiluminescent or fluorescent materials, can exploit this unique inherent property to selectively distinguish liver tumor tissues from normal tissues without additional modifications or treatments. [ABSTRACT FROM AUTHOR]

Organic phosphorescent materials are excellent candidates for use in tumor imaging. However, a systematic comparison of the effects of the intensity, lifetime, and wavelength of phosphorescent emissions on bioimaging performance has not yet been undertaken. In addition, there have been few reports on organic phosphorescent materials that specifically distinguish tumors from normal tissues. This study addresses these gaps and reveals that longer lifetimes effectively increase the signal intensity, whereas longer wavelengths enhance the penetration depth. Conversely, a strong emission intensity with a short lifetime does not necessarily yield robust imaging signals. Building upon these findings, an organo‐phosphorescent material with a lifetime of 0.94 s was designed for tumor imaging. Remarkably, the phosphorescent signals of various organic nanoparticles are nearly extinguished in blood‐rich organs because of the quenching effect of iron ions. Moreover, for the first time, we demonstrated that iron ions universally quench the phosphorescence of organic room‐temperature phosphorescent materials, which is an inherent property of such substances. Leveraging this property, both the normal liver and hepatitis tissues exhibit negligible phosphorescent signals, whereas liver tumors display intense phosphorescence. Therefore, phosphorescent materials, unlike chemiluminescent or fluorescent materials, can exploit this unique inherent property to selectively distinguish liver tumor tissues from normal tissues without additional modifications or treatments. [ABSTRACT FROM AUTHOR]

Background: The famous Tang Dynasty monk Yi Jing travelled to ancient India in 671 AD, visited more than 30 regions and returned to China in 695 AD. He wrote Nanhai Jigui Neifa Zhuan, which he completed in 691 AD. It describes the basic rules, namely 'Inner Dharma' (Neifa,内法) that Buddhist sites and monks should follow in their daily lives. Additionally, the author provided an overview of ancient Indian Buddhist medicine, covering aetiology, diagnosis, medication, acupuncture, health preservation and other aspects, which exhibited distinct characteristics. Methods: This article first delves into the original text of Nanhai Jigui Neifa Zhuan by reading it thoroughly and extracts core chapters related to hygiene, medicine and health care. Later, the extracted information is meticulously classified and organised. Lastly, through a systematic literature review, keywords search, data screening and comparative analysis, an in-depth and comprehensive exploration and analysis of Nanhai Jigui Neifa Zhuan is conducted within the domains of hygiene, medicine and health care. Results: Nanhai Jigui Neifa Zhuan emphasizes the importance of personal hygiene for ancient Indian monks and introduces the basic theories of ancient Indian medicine. It compares ancient Indian and Chinese medicinal materials, highlighting their respective roles in treating different diseases. Furthermore, it briefly discusses the storage and processing of ancient Indian medicinal materials, poisoning and toxicology, and ancient Indian health preservation ideologies. Conclusion: A comprehensive and in-depth study of traditional ancient Indian medicine, including Buddhist medicine and Ayurveda, and its application in the religious environment and communities of the Tang Dynasty (618–907 AD) aids in understanding the treatment methods and health practices of ancient Indian medicine. Additionally, it facilitates a deeper understanding of the similarities, differences and exchange between Chinese and Indian medicine, thereby opening up new horizons for future research. [ABSTRACT FROM AUTHOR]

As an omnivorous fish, wild tilapia feed on both animal and plant foods, depending on what is available. To understand the nutritional function of the gut microbiota of tilapia, we used shotgun metagenomic sequencing, untargeted metabolomics analysis, and 16S rRNA gene sequencing to study the metabolites and gut microbial communities in tilapia eating different diets (artemia nauplii in the carnivorous diet; plant‐based pelleted feed [PBP] in the herbivorous diet; and a mixture of these two in the omnivorous diet). A total of 225 Nile tilapia (Oreochromis niloticus) were cultured in nine 1500 L outdoor tanks, with three replicate tanks per diet and 25 fish per tank. β‐diversity analysis revealed that there was no significant difference in microbial structure between the three diets. However, significant differences were detected in gut metabolites. The abundance of the core bacteria in tilapia intestine (genus Cetobacterium) increased significantly when an omnivorous diet was fed. Cetobacterium abundance was significantly correlated to some differential metabolites including glucose and amino acids, and significantly correlated to pathways of carbohydrate and amino acids metabolism, identified by metagenome analysis. Metagenomic binning produced seven Cetobacterium MAGs with the completeness >50% and contamination <10%, in which genes related to the above metabolites and metabolism pathways were identified. All seven MAGs contained CAZymes that could act on distinct carbohydrates, providing highly diversified capabilities to this genus to cope with both animal and plant glycans. These tilapia fed with an omnivorous diet also showed increased growth. The differential intestinal metabolites aspartate, isoleucine, ornithine, proline, nicotinate, and NAD+ could be related to the increased growth. Our results expanded the understanding of how tilapia have adapted to an omnivorous diet and may provide knowledge for improving aquaculture management. [ABSTRACT FROM AUTHOR]

Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α‐Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α‐ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long‐standing catalysis challenge. Herein, an unprecedented TBD‐switched Pd‐catalyzed double isocyanide insertion reaction for assembling ketoamides in aqueous DMSO from (hetero)aryl halides and pseudohalides under mild conditions is reported. The effectiveness and utility of this protocol are demonstrated by its diverse substrate scope (93 examples), the ability to late‐stage modify pharmaceuticals, scalability to large‐scale synthesis, and the synthesis of pharmaceutically active molecules. Mechanistic studies indicate that TBD is a key ligand that modulates the Pd‐catalyzed double isocyanide insertion process, thereby selectively providing the desired α‐ketoamides in a unique manner. In addition, the imidoylpalladium(II) complex and α‐ketoimine amide are successfully isolated and determined by X‐ray analysis, confirming that they are probable intermediates in the catalytic pathway. [ABSTRACT FROM AUTHOR]

Nucleocytoplasmic large DNA viruses (NCLDVs; also called giant viruses), constituting the phylum Nucleocytoviricota, can infect a wide range of eukaryotes and exchange genetic material with not only their hosts but also prokaryotes and phages. A few NCLDVs were reported to encode genes conferring resistance to beta‑lactam, trimethoprim, or pyrimethamine, suggesting that they are potential vehicles for the transmission of antibiotic resistance genes (ARGs) in the biome. However, the incidence of ARGs across the phylum Nucleocytoviricota, their evolutionary characteristics, their dissemination potential, and their association with virulence factors remain unexplored. Here, we systematically investigated ARGs of 1416 NCLDV genomes including those of almost all currently available cultured isolates and high-quality metagenome-assembled genomes from diverse habitats across the globe. We reveal that 39.5% of them carry ARGs, which is approximately 37 times higher than that for phage genomes. A total of 12 ARG types are encoded by NCLDVs. Phylogenies of the three most abundant NCLDV-encoded ARGs hint that NCLDVs acquire ARGs from not only eukaryotes but also prokaryotes and phages. Two NCLDV-encoded trimethoprim resistance genes are demonstrated to confer trimethoprim resistance in Escherichia coli. The presence of ARGs in NCLDV genomes is significantly correlated with mobile genetic elements and virulence factors. Nucleocytoplasmic large DNA viruses, or 'giant viruses', infect a wide range of eukaryotes and can exchange genetic material not only with their hosts but also with bacteria and phages. Here, the authors show that many giant viruses carry diverse antibiotic resistance genes, which are associated with mobile genetic elements and genes encoding potential virulence factors. [ABSTRACT FROM AUTHOR]

Egg-laying performance is of great economic importance in poultry, but the underlying genetic mechanisms are still elusive. In this work, we conduct a multi-omics and multi-tissue integrative study in hens with distinct egg production, to detect the hub candidate genes and construct hub molecular networks contributing to egg-laying phenotypic differences. We identifiy three hub candidate genes as egg-laying facilitators: TFPI2, which promotes the GnRH secretion in hypothalamic neuron cells; CAMK2D, which promotes the FSHβ and LHβ secretion in pituitary cells; and OSTN, which promotes granulosa cell proliferation and the synthesis of sex steroid hormones. We reveal key endocrine factors involving egg production by inter-tissue crosstalk analysis, and demonstrate that both a hepatokine, APOA4, and an adipokine, ANGPTL2, could increase egg production by inter-tissue communication with hypothalamic-pituitary-ovarian axis. Together, These results reveal the molecular mechanisms of multi-tissue coordinative regulation of chicken egg-laying performance and provide key insights to avian reproductive regulation. Egg-laying performance is an important phenotype for breeding chicken. Here, the authors explore the regulatory networks driving phenotypic differences in egg-laying, and identify laying-related variants and endocrine factors. [ABSTRACT FROM AUTHOR]

A series of low-dose high-valence Ti4+ doped MIL-53-NH2(Fe) photocatalysts were synthesized for visible-light-driven CO2 reduction. The highest CO2-to-CO conversion rate of Ti4+ doped MIL-53-NH2(Fe) was 7.24 mmol g-1 h-1 and the highest CO selectivity was 94% in acetonitrile solvent using [Ru(bpy)3]2+ and triethanolamine. [ABSTRACT FROM AUTHOR]

Background: The gut-lung axis, pivotal for respiratory health, is inadequately explored in pulmonary and critical care medicine (PCCM) inpatients. Methods: Examining PCCM inpatients from three medical university-affiliated hospitals, we conducted 16S ribosomal RNA sequencing on stool samples (inpatients, n = 374; healthy controls, n = 105). We conducted statistical analyses to examine the gut microbiota composition in PCCM inpatients, comparing it to that of healthy controls. Additionally, we explored the associations between gut microbiota composition and various clinical factors, including age, white blood cell count, neutrophil count, platelet count, albumin level, hemoglobin level, length of hospital stay, and medical costs. Results: PCCM inpatients exhibited lower gut microbiota diversity than healthy controls. Principal Coordinates Analysis revealed marked overall microbiota structure differences. Four enterotypes, including the exclusive Enterococcaceae enterotype in inpatients, were identified. Although no distinctions were found at the phylum level, 15 bacterial families exhibited varying abundances. Specifically, the inpatient population from PCCM showed a significantly higher abundance of Enterococcaceae, Lactobacillaceae, Erysipelatoclostridiaceae, Clostridiaceae, and Tannerellaceae. Using random forest analyses, we calculated the areas under the receiver operating characteristic curves (AUCs) to be 0.75 (95% CIs 0.69–0.80) for distinguishing healthy individuals from inpatients. The four most abundant genera retained in the classifier were Blautia, Subdoligranulum, Enterococcus, and Klebsiella. Conclusions: Evidence of gut microbiota dysbiosis in PCCM inpatients underscores the gut-lung axis's significance, promising further avenues in respiratory health research. [ABSTRACT FROM AUTHOR]

Breast muscle growth rate and intramuscular fat (IMF) content show apparent differences between fast-growing broilers and slow-growing indigenous chickens. However, the underlying genetic basis of these phenotypic characteristics remains elusive. In this study, we investigate the dynamic alterations of three-dimensional genome architecture and chromatin accessibility in breast muscle across four key developmental stages from embryo to starter chick in Arbor Acres (AA) broilers and Yufen (YF) indigenous chickens. The limited breed-specifically up-regulated genes (Bup-DEGs) are embedded in breed-specific A compartment, while a majority of the Bup-DEGs involving myogenesis and adipogenesis are regulated by the breed-specific TAD reprogramming. Chromatin loops allow distal accessible regions to interact with myogenic genes, and those loops share an extremely low similarity between chicken with different growth rate. Moreover, AA-specific loop interactions promote the expression of 40 Bup-DEGs, such as IGF1, which contributes to myofiber hypertrophy. YF-specific loop interactions or distal accessible regions lead to increased expression of 5 Bup-DEGs, including PIGO, PEMT, DHCR7, TMEM38B, and DHDH, which contribute to IMF deposition. These results help elucidate the regulation of breast muscle growth and IMF deposition in chickens. A Hi-C study reveals the dynamic chromatin architecture of breast muscle and gene expression affected by breed-specific 3D genome architecture that may influence muscle growth and intramuscular fat deposition between fast-growing and slow-growing chickens. [ABSTRACT FROM AUTHOR]

Aliphatic quaternary ammonium salts (QASs) with intrinsic photoluminescence (PL) have drawn increasing attention due to the importance of exploring the mechanism of ionic emissive clusters, whereas it remains challenging to clarify structure–property relationships. Here, the effective modulation of photophysical properties of gemini aliphatic QASs (n‐BTADB) is managed by altering the alkyl chain length. Boosted quantum yields (up to 24.6%), prolonged phosphorescence lifetimes (up to 515.2 ms), and varied PL colors are achieved by manipulating the aggregation states of the compounds. Interlaced herringbone packing patterns and strong ionic interactions facilitate the intersystem crossing process and stabilize the triplets. The confluence of varied hydrophobic interactions and chain flexibility results in the fluctuation of phosphorescence lifetimes as the alkyl chain lengthens. Furthermore, the single‐component white‐light emission is obtained in 12‐HBTADB crystals by introducing electron‐rich hydroxyls. These results shed new light on the structure–property relationships of ionic emissive clusters and the rational design of nonconventional ionic luminophores. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: This study presents the initial findings on how rice cultivation impacts water quality and the microbial community structure in ponds where mandarin fish are being fed an artificial diet. The results indicated that rice cultivation plays a significant role in reducing nutrient salt levels in the water, thus regulating the overall aquatic environment. Furthermore, the cultivation of rice has been found to alter the composition of microbial communities in the water, leading to a decrease in diversity and affecting the abundance of bacteria involved in carbon, nitrogen, and phosphorus metabolism. The study identified Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes, and Deinococcus-Thermus as the dominant bacterial phyla in ponds where mandarin fish are being fed an artificial diet. Additionally, it was observed that Proteobacteria showed a particular preference for proliferation in the aquatic environment with rice cultivation on the water surface. These results provide a valuable foundation for the potential application of aquaculture practices involving mandarin fish fed an artificial diet and rice floating beds. The culture of mandarin fish using artificial feed has been gaining increasing attention in China. Ensuring good water quality in the ponds is crucial for successful aquaculture. Recently, the trial of pond-based rice floating beds (PRFBs) in aquaculture ponds has shown promising results. This research assessed the impact of PRFBs on the microbial community structure and overall quality of the aquaculture pond, thereby enhancing our understanding of its functions. The results revealed that the PRFB group exhibited lower levels of NH4+-N, NO2−-N, NO3−-N, TN, TP, and Alk in pond water compared to the control group. The microbial diversity indices in the PRFB group showed a declining trend, while these indices were increasing in the control group. At the phylum level, there was a considerable increase in Proteobacteria abundance in the PRFB group throughout the culture period, suggesting that PRFBs may promote the proliferation of Proteobacteria. In the PRFB group, there was a remarkable decrease in bacterial populations related to carbon, nitrogen, and phosphorus metabolism, including genera Rhodobacter, Rhizorhapis, Dinghuibacter, Candidatus Aquiluna, and Chryseomicrobium as well as the CL500_29_marine_group. Overall, the research findings will provide a basis for the application of aquaculture of mandarin fish fed an artificial diet and rice floating beds. [ABSTRACT FROM AUTHOR]

Mitochondria-associated endoplasmic reticulum membranes (MAMs) act as physical membrane contact sites facilitating material exchange and signal transmission between mitochondria and endoplasmic reticulum (ER), thereby regulating processes such as Ca2+/lipid transport, mitochondrial dynamics, autophagy, ER stress, inflammation, and apoptosis, among other pathological mechanisms. Emerging evidence underscores the pivotal role of MAMs in cardiovascular diseases (CVDs), particularly in aging-related pathologies. Aging significantly influences the structure and function of the heart and the arterial system, possibly due to the accumulation of reactive oxygen species (ROS) resulting from reduced antioxidant capacity and the age-related decline in organelle function, including mitochondria. Therefore, this paper begins by describing the composition, structure, and function of MAMs, followed by an exploration of the degenerative changes in MAMs and the cardiovascular system during aging. Subsequently, it discusses the regulatory pathways and approaches targeting MAMs in aging-related CVDs, to provide novel treatment strategies for managing CVDs in aging populations. [ABSTRACT FROM AUTHOR]

Photoluminescence (PL) colour-changing materials in response to photostimulus play an increasingly significant role in intelligent applications for their programmability. Nevertheless, current research mainly focuses on photochemical processes, with less attention to PL transformation through uniform aggregation mode adjustment. Here we show photochromic luminescence in organic crystals (e.g. dimethyl terephthalate) with PL varying from dark blue to purple, then to bright orange-red, and finally to red. This change is attributed to the emergence of clusters with red emission, which is barely achieved in single-benzene-based structures, thanks to the subtle molecular rearrangements prompted by light. Crucial to this process are the through-space electron interactions among molecules and moderate short contacts between ester groups. The irradiated crystals exhibit reversible PL transformation upon sufficient relaxation, showing promising applications in information storage and smart optoelectronic devices. This research contributes to the development of smart photochromic luminescent materials with significant PL colour transformations through molecular rearrangement. Color-changing emissions in organic crystals are often realized via photochemical reactions of their molecules. Here, the authors demonstrate reversible color change through more simple molecular rearrangements with application in encryption and data storage. [ABSTRACT FROM AUTHOR]

Asia stands out as the most populous and geographically diverse region globally. The pressing issues of water resource development and the resulting ecological impacts are exacerbated by the region's rapid population growth and economic expansion. Groundwater, a vital source of water in Asia, faces significant disparities in distribution and suffers from unsustainable exploitation practices. This study applies groundwater system theory and categorizes Asia into 11 primary groundwater systems and 36 secondary ones, based on intercontinental geological structures, climate, terrain, and hydrogeological characteristics. As of the end of 2010, Asia's assessed groundwater resources totalled 4.677x109 m3/a, with exploitable resources amounting to 3.274x109 m3/a. By considering the geological environmental impacts of groundwater development and the distinctive characteristics of terrain and landforms, six categories of effect zones with varying distribution patterns are identified. The current research on Asia's groundwater resources, environmental dynamics, and human impacts aims to provide a theoretical foundation for sustainable groundwater management and environmental conservation in the region. [ABSTRACT FROM AUTHOR]

Background: Shikonin, a purified naphthoquinone separated from a Traditional Chinese medicinal herb Lithospermum erythrorhixon, which exhibits anticancer properties. Objectives: To clarify the molecular mechanisms of therapeutic effects of shikonin against osteosarcoma. Materials and Methods: Cell Counting Kit-8 (CCK-8) assay was employed to evaluate cell viability. Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) double-staining was conducted to evaluate the apoptotic ratio of the MG-63 cells. The effects of shikonin on the invasiveness of osteosarcoma cells were implemented by a transwell cell migration assay. In the meantime, a western blot assay was employed to detect alterations in the relevant mechanism proteins within osteosarcoma cells. Molecular docking analysis was conducted to anticipate the binding interaction between shikonin and EGFR/protein kinase B (AKT)/mTOR. Results: We observed that shikonin suppressed proliferation and induced apoptosis in the MG-63 cells in a dose-dependent manner. Pursuing these findings, the potential molecular mechanisms were detected. Shikonin intervention blocked epidermal growth factor receptor (EGFR) phosphorylation and decreased epidermal growth factor (EGF)-induced activation of downstream signaling molecules, such as AKT and mammalian target of rapamycin (mTOR) in the MG-63 cells. However, the additional recombinant human epidermal growth factor (rHuEGF) could stimulate the activation of EGFR/AKT/mTOR signaling and reverse cell apoptosis caused by shikonin. Molecular docking analysis showed that shikonin presented the highest bonding ability with EGFR, AKT, and mTOR. Conclusion: Our results show that shikonin inhibits human osteosarcoma development via inactivating EGFR/AKT/mTOR signaling. It demonstrates that shikonin may act as a potential therapeutic agent in osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

Background: Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. Methods: We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. Results: The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. Conclusion: Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients. [ABSTRACT FROM AUTHOR]

Interactions between host and bacterial cells are integral to human physiology. The complexity of host–microbe interactions extends to different cell types, spatial aspects, and phenotypic heterogeneity, requiring high‐resolution approaches to capture their full complexity. The latest breakthroughs in single‐cell RNA sequencing (scRNA‐seq) have opened up a new era of studies in host–pathogen interactions. Here, we first report a high‐throughput cross‐species dual scRNA‐seq technology by using random primers to simultaneously capture both eukaryotic and bacterial RNAs (scRandom‐seq). Using reference cells, scRandom‐seq can detect individual eukaryotic and bacterial cells with high throughput and high specificity. Acinetobacter baumannii (A.b) is a highly opportunistic and nosocomial pathogen that displays resistance to many antibiotics, posing a significant threat to human health, calling for discoveries and treatment. In the A.b infection model, scRandom‐seq witnessed polarization of THP‐1 derived‐macrophages and the intracellular A.b‐induced ferroptosis‐stress in host cells. The inhibition of ferroptosis by Ferrostatin‐1 (Fer‐1) resulted in the improvement of cell vitality and resistance to A.b infection, indicating the potential to resist related infections. scRandom‐seq provides a high‐throughput cross‐species dual single‐cell RNA profiling tool that will facilitate future discoveries in unraveling the complex interactions of host–microbe interactions in infection systems and tumor micro‐environments. [ABSTRACT FROM AUTHOR]

Interactions between host and bacterial cells are integral to human physiology. The complexity of host–microbe interactions extends to different cell types, spatial aspects, and phenotypic heterogeneity, requiring high‐resolution approaches to capture their full complexity. The latest breakthroughs in single‐cell RNA sequencing (scRNA‐seq) have opened up a new era of studies in host–pathogen interactions. Here, we first report a high‐throughput cross‐species dual scRNA‐seq technology by using random primers to simultaneously capture both eukaryotic and bacterial RNAs (scRandom‐seq). Using reference cells, scRandom‐seq can detect individual eukaryotic and bacterial cells with high throughput and high specificity. Acinetobacter baumannii (A.b) is a highly opportunistic and nosocomial pathogen that displays resistance to many antibiotics, posing a significant threat to human health, calling for discoveries and treatment. In the A.b infection model, scRandom‐seq witnessed polarization of THP‐1 derived‐macrophages and the intracellular A.b‐induced ferroptosis‐stress in host cells. The inhibition of ferroptosis by Ferrostatin‐1 (Fer‐1) resulted in the improvement of cell vitality and resistance to A.b infection, indicating the potential to resist related infections. scRandom‐seq provides a high‐throughput cross‐species dual single‐cell RNA profiling tool that will facilitate future discoveries in unraveling the complex interactions of host–microbe interactions in infection systems and tumor micro‐environments. [ABSTRACT FROM AUTHOR]

Rationale: Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome. Objectives: To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes. Methods: We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data. Results: Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota. Conclusions: Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment. [ABSTRACT FROM AUTHOR]

Little is known about the relationships between human genetics and the airway microbiome. Deeply sequenced airway metagenomics, by simultaneously characterizing the microbiome and host genetics, provide a unique opportunity to assess the microbiome-host genetic associations. Here we performed a co-profiling of microbiome and host genetics with the identification of over 5 million single nucleotide polymorphisms (SNPs) through deep metagenomic sequencing in sputum of 99 chronic obstructive pulmonary disease (COPD) and 36 healthy individuals. Host genetic variation was the most significant factor associated with the microbiome except for geography and disease status, with its top 5 principal components accounting for 12.11% of the microbiome variability. Within COPD individuals, 113 SNPs mapped to candidate genes reported as genetically associated with COPD exhibited associations with 29 microbial species and 48 functional modules (P < 1 × 10−5), where Streptococcus salivarius exhibits the strongest association to SNP rs6917641 in TBC1D32 (P = 9.54 × 10−8). Integration of concurrent host transcriptomic data identified correlations between the expression of host genes and their genetically-linked microbiome features, including NUDT1, MAD1L1 and Veillonella parvula, TTLL9 and Stenotrophomonas maltophilia, and LTA4H and Haemophilus influenzae. Mendelian randomization analyses revealed a potential causal link between PARK7 expression and microbial type III secretion system, and a genetically-mediated association between COPD and increased relative abundance of airway Streptococcus intermedius. These results suggest a previously underappreciated role of host genetics in shaping the airway microbiome and provide fresh hypotheses for genetic-based host-microbiome interactions in COPD. [ABSTRACT FROM AUTHOR]

In this paper, the electrical performance of a‐Si TFT product on adjustable frequency display is studied. It is found that panel flicker behavior is related to a‐Si channel characteristics, which is related to the TFT Cgs capacitance increase at low display frequency. And it is also found that the relationship between brightness fluctuations and TFT leakage current affected by Poole‐Frenkel effect. By optimizing TFT process parameter to reduce the change of Cgs capacitance and reduce TFT leakage current in Poole‐Frenkel region, panel flicker performance is obviously improved. As a result, gaming display product can meet the G‐sync optical standard requirement. [ABSTRACT FROM AUTHOR]

The forest could be a protective structure to reduce rock avalanches in the Sichuan-Tibet Mountains. When rocks propagate down a forested slope and hit trees, they are blocked, modified in trajectory, slowed down, and deposited, which weakens their destructive effect directly on the downstream. To better understand the protective effect of forests against rock avalanches, a novel material point method (MPM) introducing two contact models describes the rock avalanches' movement on slope and interaction with trees, respectively. Carry out simulations on an idealized scenario of rock avalanches to conduct extensive parametric studies, which give the shape, volume, thickness, and runup height of rock accumulations, showing how shapes, species, and layout of trees have vital effects on blocking the rock avalanches. Finally, an optimal green protective structure for a vegetation-free slope in a 3D valley is given, and the blocking-baffle mechanism of vegetation to rock avalanches on mountains is illustrated clearly through numerical calculations. [ABSTRACT FROM AUTHOR]

Introduction Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. Methods A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. Results Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. Conclusions The findings of the present study indicate that the safety of E-cig should be further evaluated. Implications Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine. [ABSTRACT FROM AUTHOR]

Background: It has been shown that inflammation may be associated with cognitive impairment (CI). Diet modulates inflammation. However, there is currently a scarcity of epidemiological studies exploring the connection between the inflammatory potential of diet and CI. The objective was to investigate the correlation between the dietary inflammatory index (DII) and cognitive impairment in older adults in the United States. Methods: The present investigation utilized a cross-sectional dataset obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Dietary intake data was used to calculate DII scores, which were then used to categorize participants into quartiles. Participants' cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Individuals who scored in the lowest quartile on any of these tests were classified as exhibiting low cognitive performance. The association between DII and cognitive impairment was investigated by multivariate logistic regression, smooth curve fitting, and subgroup analysis. Results: A total of 947 older adults were enrolled in the study. Following the adjustment of confounding variables, DII scores exhibited a significant and positive correlation with low cognitive performance, as measured by AFT (OR 1.15, 95% CI 1.02-1.28, p = 0.02) and the DSST (OR 1.38, 95% CI 1.13-1.68, p = 0.004). Compared with the lowest quartile of DII, the highest weighted odds ratio of cognitive impairment based on AFT was observed in the fourth quartile group (OR 1.89, 95% CI 1.05-3.38, p = 0.03). Similarly, a comparable pattern was evident in DSST (OR 4.30, 95% CI 1.85-9.98, p = 0.003). Additionally, the smooth curve fitting results showed a nonlinear relationship between DII and cognitive decline evaluated by DSST (p for nonlinearity = 0.016). No interaction effects between cognitive impairment and age or gender were observed in relation to all cognitive test scores. Conclusion: This research reveals a positive link between diet with higher inflammatory potential and cognitive decline among elderly individuals in America. However, additional studies on dietary interventions are necessary to explore the cause-and-effect relationship. [ABSTRACT FROM AUTHOR]

Groundwater serves as an important water source for residents in and around mining areas. To achieve scientific planning and efficient utilization of water resources in mining areas, it is essential to figure out the chemical formation process and the ground water sulfur cycle that transpire after the coal mining activities. Based on studies of hydrochemistry and D,18O-H2O,34S-SO4 isotopes, this study applied principal component analysis, ion ratio and other methods in its attempts to reveal the hydrogeochemical action and sulfur cycle in the subsidence area of Pingyu mining area. The study discovered that, in the studied area, precipitation provides the major supply of groundwater and the main water chemistry effects are dominated by oxidation dissolution of sulfide minerals as well as the dissolution of carbonate and silicate rocks. The sulfate in groundwater primarily originates from oxidation and dissolution of sulfide minerals in coal-bearing strata and human activities. The mixed sulfate formed by the oxidation of sulfide minerals and by human activities continuously recharges the groundwater, promoting the dissolution of carbonate rock and silicate rock in the process. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the performance of the Framingham cardiovascular risk score (FRS)/pooled cohort equations (PCE)/China prediction for atherosclerotic cardiovascular disease (ASCVD) risk (China-PAR model) in a prospective cohort of Chinese older adults. Patients and Methods: We assessed 717 older adults aged 75– 85 years without ASCVD at the baseline from the Sichuan province of China. The participants were followed annually from 2011 to 2021. We obtained the participants' information through the medical records of physical examination and evaluated their 10-year ASCVD risk using FRS, PCE, and China-PAR. We further evaluated the predictive abilities of three assessment models. Results: During the 10-year follow-up, 206 participants developed ASCVD, with an incidence rate of 28.73%. The FRS and China-PAR moderately underestimated the risk of ASCVD (22.1% and 12.4%, respectively), but while PCE overestimated the risk (36.1%). FRS and China-PAR were found to underestimate the risk of ASCVD (26% and 63%, respectively) for men, while PCE overestimated the risk by 8%; For women, FRS and China-PAR were found to underestimate the risk of ASCVD (14% and 35%, respectively), while PCE overestimated the risk by 88%. Conclusion: The 10-year ASCVD risk was found to be overestimated by PCE. China-PAR had the most accurate predictions in women, while FRS was particularly well-calibrated in males. All three risk models have good discrimination, with FRS and PCE being well-calibrated in men and all three being well-calibrated in women. Therefore, accurate risk models are warranted to facilitate the prevention of ASCVD at the baseline among Chinese older adults. [ABSTRACT FROM AUTHOR]

Untethered capsules hold clinical potential for the diagnosis and treatment of gastrointestinal diseases. Although considerable progress has been achieved recently in this field, the constraints imposed by the narrow spatial structure of the capsule and complex gastrointestinal tract environment cause many openended problems, such as poor active motion and limited medical functions. In this work, we describe the development of small-scale magnetically driven capsules with a distinct magnetic soft valve made of dual-layer ferromagnetic soft composite films. A core technological advancement achieved is the flexible opening and closing of the magnetic soft valve by using the competitive interactions between magnetic gradient force and magnetic torque, laying the foundation for the functional integration of both drug release and sampling. Meanwhile, we propose a magnetic actuation strategy based on multifrequency response control and demonstrate that it can achieve effective decoupled regulation of the capsule’s global motion and local responses. Finally, through a comprehensive approach encompassing ideal models, animal ex vivo models, and in vivo assessment, we demonstrate the versatility of the developed magnetic capsules and their multiple potential applications in the biomedical field, such as targeted drug delivery and sampling, selective dual-drug release, and light/thermal-assisted therapy. [ABSTRACT FROM AUTHOR]

Hexokinase (HXK) plays a crucial role in plants, catalyzing the phosphorylation of hexose substances, which is one of the key steps in sugar metabolism and energy production. While HXK genes have been well-studied in model plants, the evolutionary and functional characteristics of HXK gene family in jujube is unknow. In this study, the HXK gene family members were identified by bioinformatics methods, the key members regulating glucose metabolism were identified by transcriptome data, and finally the function of the key genes was verified by instantaneous and stable genetic transformation. Our results showed that seven HXK genes were identified in the jujube genome, all of which were predict located in the chloroplast and contain Hexokinase-1 (PF00349) and Hexokinase-2 (PF03727) conserved domains. Most of HXK proteins were transmembrane protein with stable, lipid-soluble, hydrophilic. The secondary structure of ZjHXK proteins main a-helix, and contains two distinct tertiary structure. All ZjHXK genes contain nine exons and eight introns. Predictions of cis-regulatory elements indicate that the promoter region of ZjHXK contains a large number of MeJA responsive elements. Finally, combined with the analysis of the relationship between the expression and glucose metabolism, found that ZjHXK5 and ZjHXK6 may the key genes regulating sugar metabolism. Transient overexpression of ZjHXK5 and ZjHXK6 on jujube, or allogeneic overexpression of ZjHXK5 and ZjHXK6 on tomato would significantly reduce the content of total sugar and various sugar components. Transient silencing of ZjHXK5 and ZjHXK6 genes results in a significant increase in sucrose and total sugar content. Interestingly, the expression of ZjHXK5 and ZjHXK6 were also affected by methyl jasmonate. [ABSTRACT FROM AUTHOR]

In the field of social networks rumor control, finding the important nodes with the greatest propagating influence is of great practical importance to effectively control the propagation of rumors. In order to solve the problem that the network coupling information and information transfer mechanism in the existing node importance metric affects the accuracy of the metric, we propose a measure of node importance based on multiple feature fusion (MFF). The method uses an improved Dempster–Shafer evidence theory to fuse the centrality, transmissibility, and prestige measurement of nodes and rank the importance of nodes based on the fusion results. The proposed method was first evaluated against similar methods on six real networks in terms of robustness and vulnerability, as well as in terms of SIR propagation characteristics. Then, we simulated the changes in the number of users who believed the rumor after the rumor was propagated in three cases: before the control, after suppress rumors by random nodes, and after suppress rumors by important nodes. The experimental results show that the proposed method is more accurate for node importance measurement and more effective in rumor control. [ABSTRACT FROM AUTHOR]

Polymer‐based room‐temperature phosphorescence (RTP) materials, especially polysaccharide‐based RTP materials, earn sustained attention in the fields of anti‐counterfeiting, data encryption, and optoelectronics owing to their green regeneration, flexibility, and transparency. However, those with both ultralong phosphorescence lifetime and excitation wavelength‐dependent afterglow are rarely reported. Herein, a kind of amorphous RTP material with ultralong lifetime of up to 2.52 s is fabricated by covalently bonding sodium alginate (SA) with arylboronic acid in the aqueous phase. The resulting polymer film exhibits distinguished RTP performance with excitation‐dependent emissions from cyan to green. Specifically, by co‐doping with other fluorescent dyes, further regulation of the afterglow color from cyan to yellowish‐green and near‐white can be achieved through triplet‐to‐singlet Förster resonance energy transfer. In addition, the water‐sensitive properties of hydrogen bonds endow the RTP property of SA‐based materials with water/heat‐responsive characteristics. On account of the color‐tunable and stimuli‐responsive afterglows, these smart materials are successfully applied in data encryption and anti‐counterfeiting. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is the leading cause of death in patients with sepsis syndrome and without effective protective or therapeutic treatments. Acacetin, a natural dietary flavonoid, reportedly exerts several biological effects, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, acacetin's effect and underlying mechanism on sepsis-induced ALI remain unclear. Here, the mouse model was established to explore the impact of acacetin on sepsis-induced ALI. Acacetin significantly increased ALI murine survival and attenuated lung injury in histological examinations. Additionally, acacetin down-regulated myeloperoxidase activity, protein concentration, and number of neutrophils and macrophages in bronchoalveolar lavage fluid. Subsequently, inflammatory cytokines, including TNF-α, IL-1β, and IL-6, were examined. Results showed that acacetin dramatically suppressed the production of TNF-α, IL-1β, and IL-6. These above results indicated that acacetin attenuated sepsis-induced ALI by inhibiting the inflammatory response. Moreover, acacetin inhibited the expression of markers for M1-type (iNOS, CD86) macrophages and promoted the expression of markers for M2-type (CD206, Arg1) macrophages by western blot. In addition, acacetin down-regulated the expression TRAF6, NF-κB, and Cyclooxygenase-2 (COX2) by western blot. The high concentration of acacetin had a better effect than the low concentration. Besides, over-expression of TRAF6 up-regulated the expression of COX2, CD86, and iNOS, and the ratio of p-NF-κB to NF-κB increased the mRNA levels of TNF-α, IL-1β, and IL-6, down-regulated the expression of CD206 and Arg1. The effects of TRAF6 were the opposite of acacetin. And TRAF6 could offset the impact of acacetin. This study demonstrated that acacetin could prevent sepsis-induced ALI by facilitating M2 macrophage polarization via TRAF6/NF-κB/COX2 axis. [ABSTRACT FROM AUTHOR]

Glaciers continue to erode and transport material, forming an accumulation area at the front of the glacier. The trunk glacier, which has many tributary glaciers upstream and converges on the main channel, deposits vast amounts of material in the main channel. It blocks the main channel, forming barrier lakes, and eventually turns into mountain disasters, such as debris flows or outburst floods. Therefore, the accumulation rate of the material is a major parameter in such disasters and can determine the frequency of disasters. The material usually comes from bedrock erosion by glaciers, weathering of bedrock walls, and upstream landslides, and the material loss depends on river erosion. Based on this, we set up a method to calculate the material accumulation rate in the glacier front based on satellite images. Then, the Peilong catchment was taken as an example to validate the proposed method. The results indicate that climatic fluctuations may increase landslides, resulting in more actual accumulation than the calculated value according to the average rate of bedrock retreat. The material provided by the retreat of bedrock accounts for 92% of the total volume. Our method provides a practical reference for the mid- and long-term prediction of glacial catastrophic mass movement, as global warming seriously threatens glacier instability and downstream communities. [ABSTRACT FROM AUTHOR]

To evaluate the efficiency and long-term renal function of nephron sparing surgery (NSS) in unilateral WT patients compared with radical nephrectomy (RN). The review was performed following Cochrane Handbook guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched five databases (Pubmed, Embase, Scopus, Web of Science and Cochrane) for studies reporting the efficiency and late renal function of NSS and/or RN on February 10, 2023. Comparative studies were evaluated by Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) and RoB 2.0. Assessed outcomes included survival rate, relapse rate, eGFR, renal dysfunction and hypertension. 26 studies involving 10322 unilateral WT cases underwent RN and 657 unilateral WT cases underwent NSS were enrolled. Overall effect estimates demonstrated that NSS significantly increased eGFR at follow-up (SMD, 0.38; 95% CI 0.05-0.72; p = 0.025) compared to that at diagnosis, and RN did not significantly decrease eGFR at follow-up (SMD, − 0.33; 95% CI − 0.77–0.11; p = 0.142) compared to that at diagnosis. Moreover, no significant difference was found in outcomes of survivability (OR, 1.38; 95% CI 0.82–2.32; p = 0.226), recurrence (OR, 0.62; 95% CI 0.34–1.12; p = 0.114), eGFR at follow-up (SMD, 0.16; 95% CI − 0.36–0.69; p = 0.538), renal dysfunction (OR, 0.36; 95% CI 0.07–1.73; p = 0.200) and hypertension (OR, 0.17; 95% CI 0.03–1.10; p = 0.063). Current evidence suggests that NSS is safe and effective for unilateral WT patients, because it causes better renal function and similar oncological outcomes compared with RN. Future efforts to conduct more high-quality studies and explore sources of heterogeneity is recommended. [ABSTRACT FROM AUTHOR]

Objective: To explore the anti-inflammatory effects of ethyl lithospermate in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine-derived macrophages and zebrafish, and its underlying mechanisms. Methods: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays were performed to investigate the toxicity of ethyl lithospermate at different concentrations (12.5–100 µ mol/L) in RAW 264.7 cells. The cells were stimulated with LPS (100 ng/mL) for 12 h to establish an inflammation model in vitro, the production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α (TNF-α) were assessed by enzyme linked immunosorbent assay (ELISA). Western blot was used to ascertain the protein expressions of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) p65, phospho-STAT3 (p-STAT3, Tyr705), inhibitor of NF-κB (IκB) α, and phospho-I κB α (p-IκB α, Ser32), and confocal imaging was used to identify the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705). Additionally, the yolk sacs of zebrafish (3 days post fertilization) were injected with 2 nL LPS (0.5 mg/mL) to induce an inflammation model in vivo. Survival analysis, hematoxylin-eosin (HE) staining, observation of neutrophil migration, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to further study the anti-inflammatory effects of ethyl lithospermate and its probable mechanisms in vivo. Results: The non-toxic concentrations of ethyl lithospermate have been found to range from 12.5 to 100 µ mol/L. Ethyl lithospermate inhibited the release of IL-6 and TNF-α(P<0.05 or P<0.01), decreased IκBα degradation and phosphorylation (P<0.05) as well as the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705) in LPS-induced RAW 264.7 cells (P<0.01). Ethyl lithospermate also decreased inflammatory cells infiltration and neutrophil migration while increasing the survival rate of LPS-stimulated zebrafish (P<0.05 or P<0.01). In addition, ethyl lithospermate also inhibited the mRNA expression levels of of IL-6, TNF-α, IκBα, STAT3, and NF-κB in LPS-stimulated zebrafish (P<0.01). Conclusion: Ethyl lithospermate exerts anti-Inflammatory effected by inhibiting the NF-κB and STAT3 signal pathways in RAW 264.7 macrophages and zebrafish. [ABSTRACT FROM AUTHOR]

The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus–predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis. [ABSTRACT FROM AUTHOR]

Background: Modern breeding strategies have resulted in significant differences in muscle mass between indigenous chicken and specialized broiler. However, the molecular regulatory mechanisms that underlie these differences remain elusive. The aim of this study was to identify key genes and regulatory mechanisms underlying differences in breast muscle development between indigenous chicken and specialized broiler. Results: Two time-series RNA-sequencing profiles of breast muscles were generated from commercial Arbor Acres (AA) broiler (fast-growing) and Chinese indigenous Lushi blue-shelled-egg (LS) chicken (slow-growing) at embryonic days 10, 14, and 18, and post-hatching day 1 and weeks 1, 3, and 5. Principal component analysis of the transcriptome profiles showed that the top four principal components accounted for more than 80% of the total variance in each breed. The developmental axes between the AA and LS chicken overlapped at the embryonic stages but gradually separated at the adult stages. Integrative investigation of differentially-expressed transcripts contained in the top four principal components identified 44 genes that formed a molecular network associated with differences in breast muscle mass between the two breeds. In addition, alternative splicing analysis revealed that genes with multiple isoforms always had one dominant transcript that exhibited a significantly higher expression level than the others. Among the 44 genes, the TNFRSF6B gene, a mediator of signal transduction pathways and cell proliferation, harbored two alternative splicing isoforms, TNFRSF6B-X1 and TNFRSF6B-X2. TNFRSF6B-X1 was the dominant isoform in both breeds before the age of one week. A switching event of the dominant isoform occurred at one week of age, resulting in TNFRSF6B-X2 being the dominant isoform in AA broiler, whereas TNFRSF6B-X1 remained the dominant isoform in LS chicken. Gain-of-function assays demonstrated that both isoforms promoted the proliferation of chicken primary myoblasts, but only TNFRSF6B-X2 augmented the differentiation and intracellular protein content of chicken primary myoblasts. Conclusions: For the first time, we identified several key genes and dominant isoforms that may be responsible for differences in muscle mass between slow-growing indigenous chicken and fast-growing commercial broiler. These findings provide new insights into the regulatory mechanisms underlying breast muscle development in chicken. [ABSTRACT FROM AUTHOR]

The advent of biotechnology has expedited the understanding of the biochemistry of deoxyribonucleic acids (DNA). In the past, DNA are thought to be present only in cell nucleus as bearers of the genetic code. With the identification of extracellular DNA in circulating body fluids, DNA are now utilized, at least experimentally, for diagnosis and treatment of diseases. Extracellular DNA of host origin trigger immune responses, and are closely linked to autoimmune disease, cancer‐related inflammation, bacteria adhesion and thrombosis. Recent advancements in DNA nanotechnology have led to the development of a series of DNA‐based materials for treating diseases because of their structural programmability. Current discussions on biosafety and immunogenicity of artificial DNA materials are insufficient. This issue severely restricts the clinical translation of these novel biotechnologies. The present review attempts to bridge the gap between natural extracellular DNA and their derivatives, DNA‐based materials. The pathological attributes of endogenous extracellular DNA motivate the design of targeting DNA materials. In addition, the fate of exogenous DNA in the host inspires the optimization of DNA materials in reducing immune rejection. These bioinspired strategies provide the blueprint for utilizing DNA materials in the management of diseases that are currently challenging to diagnose or treat. [ABSTRACT FROM AUTHOR]

3,3′-Diselenodipropionic acid (DSePA), a synthetic organoselenium compound, has received considerable attention because of its antioxidant properties and safety. Its protective effect against dextran sodium sulfate (DSS)–induced mouse ulcerative colitis (UC) and the role of T helper 17 (Th17) cell proliferation were investigated. Fifty C57BL/6 male mice were randomly assigned to one of five groups: control (Con), DSePA, DSS, low-dose DSePA (LSe), and high-dose DSePA (HSe). Mice in the DSS, LSe, and HSe groups drank 2% DSS to induce UC, and received normal saline, 1 and 2 mg/mL DSePA solution by intraperitoneal injection, respectively. The DSePA group only received 2 mg/mL DSePA solution. After 5 weeks, DSS challenge induced UC in the mice, which manifested as decreased body weight, shortened colon length, the loss of goblet cells, activated proliferating cells, and multiple signs of intestinal lesions by histological observation, all of which were reversed to varying degrees by DSePA administration. DSS upregulated the colonic protein expression of the macrophage marker F4/80 and proinflammatory cytokines (IL-1β, IL-6, and TNFα), whereas DSePA administration downregulated the expression of these factors. DSS upregulated the mRNA expression of retinoic acid receptor–related orphan receptor γt (RORγt, mainly expressed in Th17 cells), IL-17A, and IL-17F and the levels of IL-17A and IL-17F in the colon, whereas DSePA administration decreased them. No difference was observed between the Con group and the DSePA group without DSS induction. Thus, DSePA administration ameliorated DSS-induced UC by regulating Th17-cell proliferation and the secretion of proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

While the majority of nonconventional luminophores consist of electron‐rich heteroatoms, an emerging category with electron‐deficient atoms (e. g. boron) have gained much attention. In this work, we focused on one of the most common boron‐containing substances, namely bis(pinacolato)diboron (BE1) and its analogue bis(2,4‐dimethylpentane‐2,4‐glycolato)diboron (BE2), whose empty p‐orbitals of boron atoms and p‐orbitals with lone pairs of oxygens form π frameworks. Both compounds are nonemissive in dilute solutions but depict remarkable photoluminescence (PL) at aggregate states, featuring aggregation‐induced emission characteristics. Additionally, their PL can be easily tuned by various external factors, such as excitation wavelength, compression, and oxygen. These photophysical properties could well be explained by the clustering‐triggered emission (CTE) mechanism. [ABSTRACT FROM AUTHOR]