Interleukin- (IL-) 38 is an emerging cytokine with multiple functions involved in infection and immunity. However, the potential role of IL-38 in the host immune response during sepsis remains ...elusive. Herein, we investigated if macrophages in septic mice express IL-38, the molecular mechanisms behind its expression, and the downstream effects of its expression. In mouse peritoneal macrophages, lipopolysaccharide (LPS) upregulated IL-38 and its receptor IL-36R, and the resulting IL-38 shifted macrophages from a M1 to M2 phenotype. Moreover, exposure to IL-38 alone was sufficient to inhibit macrophage apoptosis and LPS-driven activation of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome. These effects were partly abrogated by IL-38 downregulation. In septic mice, IL-38 markedly lowered serum concentrations of proinflammatory cytokines and greatly improved survival. Conversely, IL-38 blockade aggravated their mortality. Collectively, these findings present IL-38 as a potent immune modulator that restrains the inflammatory response by suppressing macrophage apoptosis and activation of the NLRP3 inflammasome. IL-38 may help protect organs from sepsis-related injury.
Circulating tumour DNA (ctDNA) in blood plasma is an emerging tool for clinical cancer genotyping and longitudinal disease monitoring
. However, owing to past emphasis on targeted and low-resolution ...profiling approaches, our understanding of the distinct populations that comprise bulk ctDNA is incomplete
. Here we perform deep whole-genome sequencing of serial plasma and synchronous metastases in patients with aggressive prostate cancer. We comprehensively assess all classes of genomic alterations and show that ctDNA contains multiple dominant populations, the evolutionary histories of which frequently indicate whole-genome doubling and shifts in mutational processes. Although tissue and ctDNA showed concordant clonally expanded cancer driver alterations, most individual metastases contributed only a minor share of total ctDNA. By comparing serial ctDNA before and after clinical progression on potent inhibitors of the androgen receptor (AR) pathway, we reveal population restructuring converging solely on AR augmentation as the dominant genomic driver of acquired treatment resistance. Finally, we leverage nucleosome footprints in ctDNA to infer mRNA expression in synchronously biopsied metastases, including treatment-induced changes in AR transcription factor signalling activity. Our results provide insights into cancer biology and show that liquid biopsy can be used as a tool for comprehensive multi-omic discovery.
Caregivers of advanced cancer patients face challenges impacting their quality of life (QoL). While evidence suggests that family sense of coherence (FSOC) can enhance individual psychological ...well-being and reduce distress symptoms, the precise mechanism through which FSOC improves caregivers' QoL remains unclear. This study aimed to explore the relationships among FSOC, psychological resilience, psychological distress, and QoL in primary caregivers of advanced cancer patients. A cross-sectional observational study was undertaken from June 2020 to March 2021 across five tertiary hospitals in China. Instruments included a general characteristic questionnaire, the Family Sense of Coherence Scale, the Patient Health Questionnaire-4, the 10-item Connor-Davidson Resilience Scale, and the 8-item SF-8 health survey. Pearson's correlation and chain mediation analyses were performed using IBM SPSS (version 21) and PROCESS macro (version 3.4). Out of 290 valid questionnaires, results demonstrated that FSOC directly and positively influences caregivers' QoL. Psychological distress partially mediated the FSOC-QoL association, with paths "FSOC-psychological distress-QoL" and "FSOC-psychological resilience-psychological distress-QoL" contributing 43.08% and 6.72% of the total effect, respectively. Furthermore, this study distinguished physical and mental aspects of QoL, confirming both conform to the chain mediation model. FSOC impacts caregivers' QoL directly and indirectly through the mediation of psychological distress and the chain mediation effect of "psychological resilience-psychological distress". These insights enhance our understanding of the complex interplay between FSOC and QoL, underscoring the potential benefits of bolstering FSOC to strengthen caregiver resilience, alleviate distress, and ultimately elevate their QoL.
Pure rutile nanorods were synthesized by hydrolysis of TiCl4 ethanolic solution in water at 50 °C. The assembly of rutile nanorods could be controlled through simply changing the molar ratios of ...TiCl4, ethanol, and water, resulting in different superstructures with flower- or urchinlike morphologies. The resulting samples were characterized with X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, nitrogen sorption, and UV−vis diffuse reflectance spectrum. A possible mechanism for the growth and assembly of rutile nanorod superstructures was proposed on the basis of characterization results. More importantly, we found that those low temperature synthesized superstructures showed significantly higher photocatalytic activities than commercial photocatalyst P25 on degradation of rhodamine B in water under artificial solar light. This study provides a simple and inexpensive way to prepare high active rutile nanorods superstructures photocatalysts on a large scale.
Liver cancer is the fastest growing cause of cancer deaths in the United States due to its aggressiveness and lack of effective therapies. The current preclinical study examines valeric acid ...(pentanoic acid C5H10O2), one of the main compounds of valerian root extract, for its therapeutic use in liver cancer treatment. Anticancer efficacy of valeric acid was tested in a series of in vitro assays and orthotopic xenograft mouse models. The molecular target of valeric acid was also predicted, followed by functional confirmation. Valeric acid has a broad spectrum of anticancer activity with specifically high cytotoxicity for liver cancer in cell proliferation, colony formation, wound healing, cell invasion, and 3D spheroid formation assays. Mouse models further demonstrate that systematic administration of lipid-based nanoparticle-encapsulated valeric acid significantly reduces the tumor burden and improves survival rate. Histone deacetylase (HDAC)-inhibiting functions of valeric acid are also revealed by a structural target prediction tool and HDAC activity assay. Further transcriptional profiling and network analyses illustrate that valeric acid affects several cancer-related pathways that may induce apoptosis. In summary, we demonstrate for the first time that valeric acid suppresses liver cancer development by acting as a potential novel HDAC inhibitor, which warrants further investigation on its therapeutic implications.
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This study demonstrates the viability of an active compound from valerian root extract as a novel chemotherapeutic for the treatment of hepatocellular carcinoma. We show that valeric acid suppresses liver cancer development in a series of in vitro assays and in orthotopic xenograft mouse models, possibly by acting as a novel histone deacetylase inhibitor.
This work demonstrates the effect of atomic layer deposited (ALD) Al2O3 on the reactivation of dissolved polysulfides in Li–S batteries. A 0.5nm thick layer of Al2O3 is conformally coated onto highly ...porous carbon cloth by ALD, and then assembled in a Li–S battery between the sulfur cathode and the anode side (separator and Li anode) to function as a reactivation component. Compared to half cells with no ALD treatment, the ultrathin Al2O3 coating increases the specific discharge capacity by 25% from 907 to 1136mAh/g at the 1st cycle, and by 114% from 358 to 766mAh/g at the 40th cycle. Thus the ALD-Al2O3 improves the initial specific capacity and stabilizes the cycle life remarkably. Scanning electron microscopy and energy-dispersive X-ray spectroscopy results indicate that the ALD-Al2O3 coated carbon cloth sorbs (adsorbs/absorbs) more dissolved sulfur species from the electrolyte. Potential mechanisms for the improved sorption properties are proposed. The combination of an ultrathin ALD-oxide coating with highly porous carbons presents a new strategy to improve the performance of Li–S batteries.
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•Propose a concept that recollection/reactivation, instead of confinement (usually used), of dissolved polysulfidesfor improvement of Li-S battery performance.•Combination of atomic layer deposition (ALD) with nanoporousactive carbon to engineer the surface chemistryand pore size to enhance the sorption (absorption and adsorption) of lithium polysulfides.•Development of sulfur cathode configuration for next generation of rechargeable batteries with high energy and long cycling life.
An increasing observation of in-situ production of branched glycerol dialkyl glycerol tetraethers (brGDGTs) in marine environments has aroused concerns about the utility of BIT (the ratio of brGDGTs ...over isoGDGTs) index to indicate soil contribution in marine environment. In this study, GDGT biomarkers and foraminiferal carbon isotope (δ13C) are analyzed in a mid-to-late Holocene sediment core from the northern South China Sea (SCS). The BIT values exhibited an overall similar pattern as compared to Δδ13C(P-G) (the δ13C difference between subsurface and surface planktonic foraminifera) index that indicates water column productivity, implying that the variations in BIT are likely related to marine productivity status. A positive relation between BIT and Δδ13C(P-G) was observed and explained by the downward transport of organic matter due to change of upper water mixing, with higher BIT Δδ13C(P-G) values during strengthened upper water mixing. Despite these findings, further investigations on the mechanistic processes that regulate the productions and dynamics of brGDGTs and isoGDGTs in marine sediments are warranted.
Human health problems and formaldehyde emission from wood-based composites are some of the major drawbacks of the traditional synthetic adhesives such as urea formaldehyde resins. There have been ...many attempts to decrease formaldehyde emission and replace urea formaldehyde resins with bio-based adhesives for wood-based composites. Because of some weakness in soy-based adhesive, chemicals have been used as modifiers. Modified soy-based adhesives without any formaldehyde have been successfully used to prepare wood panels. To achieve this, different synthetic cross-linking chemicals such as phenol formaldehyde resins and polyamidoamine-epichlorohydrin were used. However, in reality, what we need are totally green adhesives that use natural materials. In our previous research work, the use of tannins in combination with soy-based adhesives to make wood composites was investigated. Thus, in this research work, the feasibility of using three types of natural tannins (quebracho, mimosa and chestnut tannins) as cross-linking materials for soy adhesive was studied. The chemical bond formation and adhesion behaviors of tannin-modified soy adhesives were also investigated by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-ToF-MS) and thermo-mechanical analysis (TMA). The results showed that at ambient temperature, both ionic and covalent bonds formed between tannin constituents and amino acids; however, at higher temperature, covalent bonds are largely predominate. Based on the results obtained from the thermo-mechanical analysis, the modulus of elasticity (MOE) of soy adhesive is increased by adding tannins to its formulation. In addition, the chemical bond formation was proved by MALDI-ToF-MS.
Robust molecule–metal linkages are essential for developing high-performance and air-stable devices for molecular and organic electronics. In this work, we report a facile method for forming robust ...and covalent bonding contacts between unprotected terminal acetylenes and metal (Ag) interfaces. Using this approach, we study the charge transport properties of conjugated oligophenylenes with covalent metal–carbon contacts to silver electrodes formed from unprotected terminal acetylene anchors. We performed single molecule charge transport experiments and molecular simulations on a series of arylacetylenes using gold and silver electrodes. Our results show that molecular junctions on silver electrodes spontaneously form silver–carbynyl carbon (Ag–C) contacts, resulting in a nearly 10-fold increase in conductance compared to the same molecules on gold electrodes. Overall, this work presents a simple, new electrode–anchor pair that reliably forms molecular junctions with stable and robust contacts for molecular electronics.
In this paper, conjugated conductive polymer polypyrrole molecules were coated on Ag3PO4 nanoparticles by chemical adsorption method. The photocatalytic activity of Ag3PO4 @polypyrrole (Ag3PO4 @PPy) ...was enhanced significantly with introducing PPy. Under visible light, Ag3PO4 @PPy (1.5 wt%) degraded 100 % of phenol in 12 min and 98.39 % of 2,4-dichlorophenol in 24 min, which was 2.01 times and 1.89 times higher than pure Ag3PO4, respectively. In addition, the degradation activity of core-shell structure catalyst Ag3PO4 @PPy remains 91.26 % after five cycles. The increased stability and activity of as-prepared core-shell Ag3PO4 @PPy was mainly attributed to the synergistic effect of Ag3PO4 and PPy. The high-stability PPy shell inhibits the dissolution of Ag3PO4 nanoparticles. The core-shell structure increases the contact area and a chemical bond was formed on the interface. In addition, the matched energy level structure and the outstanding charge transfer ability of PPy conjugated large π bond accelerates the photo-generated charge separation thereby improves the photoactivity and stability of Ag3PO4.
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