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Objectives: Tumor‐associated neutrophils (TANs) are among the most abundant inflammatory cells in tumor microenvironment (TME). Aldehyde dehydrogenase 3A1 (ALDH3A1) is significantly reduced in oral squamous cell carcinoma (OSCC), ALDH3A1 overexpression suppresses tumorigenesis by inhibiting inflammation. This study investigated the relationship and mechanisms underlying the crosstalk between ALDH3A1 and TANs in OSCC. Materials and Methods: Immunohistochemistry and immunofluorescence were performed to investigate the abundance of TANs and the expression of ALDH3A1. dHL‐60 were induced with tumor‐conditioned media and recombinant IL‐6/IL‐8. The expression of key proteins in PI3K/AKT/NF‐κB pathway were detected by RT‐PCR and western blot. A xenograft model was utilized to examine the effect of ALDH3A1 on tumorigenicity and polarization of TANs. Results: In patients with OSCC, TANs significantly increased and were associated with a worse prognosis. Additionally, ALDH3A1 negatively correlated with TANs infiltration and especially the N2 phenotype which was the prominent part in OSCC. Furthermore, our study demonstrated that tumor‐derived IL‐8 drives ALDH3A1‐mediated TANs N2 polarization in the TME through PI3K/AKT/NF‐κB pathway in vitro and in vivo. Conclusion: Our results indicate that TANs can serve as a prognostic biomarker and ALDH3A1 could be a promising therapeutic target for regulating TANs N2 polarization in antitumor therapy. [ABSTRACT FROM AUTHOR]

Owing to the significant attention directed toward alloy metal nanoclusters, it is crucial to explore the relationship between their structures and their performance during the electrocatalytic CO2 reduction reaction (eCO2RR) and discover potential synergistic effects for the design of novel functional nanoclusters. However, a lack of suitable analogs makes this investigation challenging. In this study, we synthesized a well‐defined pair of structural analogs, [Au8Cu1(SAdm)4(Dppm)3Cl]2+ and [Au8Ag1(SAdm)4(Dppm)3Cl]2+ (Au8Cu1 and Au8Ag1, respectively), and characterized them. Single‐crystal X‐ray diffraction analysis revealed that Au8M1 (M=Cu/Ag) consists of a tetrahedral Au3M1 core capped by three (Dppm)Au staples, one Au2(SR)3 staple, one lone SR ligand, and a terminal Cl ligand. Ag and Cu were doped at the same site in the Au8M1 nanoclusters, which has rarely been reported. Au8Cu1 exhibited a significantly higher CO Faradaic efficiency (FECO; ~82.2 %) during eCO2RR than that of Au8Ag1 (FECO; ~33.1 %). Density functional theory calculations demonstrated that *COOH is the key intermediate in the reduction of CO2 to CO. The formation of *COOH on Au8Cu1 is more thermodynamically stable than on Au8Ag1, and Au8Cu1 shows a smaller *CO formation energy than that on Au8Ag1, which promotes the reduction of CO2. We believe that the structural analogs Au8Cu1 and Au8Ag1 offer a suitable template for the in‐depth investigation of structure‐property correlations at the atomic level. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro‐inflammatory cytokine interleukin (IL)‐1β, IL‐6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF‐κB) subunit p65 by DHEA and weakened the transcriptional activity of NF‐κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF‐κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2‐Foxo1‐GSH‐NF‐κB pathway. [ABSTRACT FROM AUTHOR]

Celastrol, a bioactive molecule extracted from the plant Tripterygium wilfordii Hook F., possesses anti‐inflammatory, anti‐obesity and anti‐tumour properties. Despite its efficacy in improving erythema and scaling in psoriatic mice, the specific therapeutic mechanism of celastrol in atopic dermatitis (AD) remains unknown. This study aims to examine the role and mechanism of celastrol in AD using TNF‐α‐stimulated HaCaT cells and DNCB‐induced Balb/c mice as in vitro and in vivo AD models, respectively. Celastrol was found to inhibit the increased epidermal thickness, reduce spleen and lymph node weights, attenuate inflammatory cell infiltration and mast cell degranulation and decrease thymic stromal lymphopoietin (TSLP) as well as various inflammatory factors (IL‐4, IL‐13, TNF‐α, IL‐5, IL‐31, IL‐33, IgE, TSLP, IL‐17, IL‐23, IL‐1β, CCL11 and CCL17) in AD mice. Additionally, celastrol inhibited Ezrin phosphorylation at Thr567, restored mitochondrial network structure, promoted translocation of Drp1 to the cytoplasm and reduced TNF‐α‐induced cellular reactive oxygen species (ROS), mitochondrial ROS (mtROS) and mitochondrial membrane potential (MMP) production. Interestingly, Mdivi‐1 (a mitochondrial fission inhibitor) and Ezrin‐specific siRNAs lowered inflammatory factor levels and restored mitochondrial reticular formation, as well as ROS, mtROS and MMP production. Co‐immunoprecipitation revealed that Ezrin interacted with Drp1. Knocking down Ezrin reduced mitochondrial fission protein Drp1 phosphorylation and Fis1 expression while increasing the expression of fusion proteins Mfn1 and Mfn2. The regulation of mitochondrial fission and fusion by Ezrin was confirmed. Overall, celastrol may alleviate AD by regulating Ezrin‐mediated mitochondrial fission and fusion, which may become a novel therapeutic reagent for alleviating AD. [ABSTRACT FROM AUTHOR]

Background: A 19‐year‐old female patient presented at 2 years of age with dysarthria, incoherent speech, and unsteady ambulation. She is prone to leaning backward when walking and has involuntary movements of the whole body. Besides, she has poor numeracy skills. She has been diagnosed with Wilson's disease (WD) in China and Japan. Objective: The objective of this study was to further clarify the diagnosis of this patient. Methods: The patient and her parents were detected with whole‐exome sequencing. Results: Based on the genetic test results, genetic analyses, and clinical manifestations, a diagnosis of WD in this patient was ruled out. The patient was eventually diagnosed with neurodevelopmental disorder with involuntary movements. Conclusions: This study reinterprets the genetic test results of a young female patient and leads to reflections on the genetic diagnostic criteria for WD: the Leipzig score is suitable for the diagnosis of most WD patients, and the genetic testing section of the score is of great diagnostic value. However, in some special cases, the proband and their first‐degree relatives should further complete cosegregation analysis to determine the origin of the lesion gene and to verify the reliability of the genetic test. In addition, this study suggests that further improving the scoring rules of the gene testing part of the Leipzig scoring system may be more helpful in achieving an accurate diagnosis of WD. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Herein, a remarkable achievement in the synthesis and characterization of an atomically precise copper‐hydride nanocluster, [Cu41(SC6H3F2)15Cl3(P(PhF)3)6(H)25]2− via a mild one‐pot reaction is presented. Through X‐ray crystallography analysis, it is revealed that [Cu41(SC6H3F2)15Cl3(P(PhF)3)6(H)25]2− exhibits a unique shell–core–shell structure. The inner Cu29 kernel is composed of three twisted Cu13 units, connected through Cu4 face sharing. Surrounding the metal core, two Cu6 metal shells, resembling a protective sandwich structure are observed. This arrangement, along with intracluster π···π interactions and intercluster C─H···F─C interactions, contributes to the enhanced stability of [Cu41(SC6H3F2)15Cl3(P(PhF)3)6(H)25]2−. The presence, number, and location of hydrides within the nanocluster are established through a combination of experimental and density functional theory investigations. Notably, the addition of a phosphine ligand triggers a fascinating nanocluster‐to‐nanocluster transformation in [Cu41(SC6H3F2)15Cl3(P(PhF)3)6(H)25]2−, resulting in the generation of two nanoclusters, [Cu14(SC6H3F2)3(PPh3)8H10]+ and [Cu13(SC6H3F2)3(P(PhF)3)7H10]0. Furthermore, it is demonstrated that [Cu41(SC6H3F2)15Cl3(P(PhF)3)6(H)25]2− exhibits catalytic activity in the hydrogenation of nitroarenes. This intriguing nanocluster provides a unique opportunity to explore the assembly of M13 units, similar to other coinage metal nanoclusters, and investigate the nanocluster‐to‐nanocluster transformation in phosphine and thiol ligand co‐protected copper nanoclusters. [ABSTRACT FROM AUTHOR]

Background: Withering is the first processing procedure of beauty tea, and there are few reports on the impact of withering methods on the quality of beauty tea and its regulatory mechanisms. Results: Through comparison of fresh tea leaves (FT) with the leaves after indoor natural withering for 18 h (IWT‐18) and outdoor solar withering for 6 h (OWT‐6), which were collected at the end of the two withering processes, 17 282 and 13 984 differentially expressed genes (DEGs) were respectively screened and 267 and 154 differential metabolites (DMs) were respectively identified. The coexpression network revealed that a large number of DEGs and DMs were enriched in phenylpropanoid, flavonoid, and adenosine triphosphate binding cassette (ABC) transporter pathways, and the number of DMs and DEGs in IWT‐18 versus FT exceeded that in OWT‐6 versus FT. Both withering methods promoted a significant increase in content of phenylalanine and upregulation of β‐glucoside expression in the phenylpropanoid metabolism pathway. Five theaflavin‐type proanthocyanidins in the flavonoid synthesis pathway were more significantly accumulated in FT versus IWT‐18 than in FT versus OWT‐6. Meanwhile, both withering methods can affect the ABC transporter pathway to promote the accumulation of amino acids and their derivatives, but different withering methods affect different ABC transporter families. Outdoor withering with more severe abiotic stress has a greater impact on the ABCG family, whereas indoor withering has a more significant effect on the ABCC family. Sensory evaluation results showed that the dry tea of IWT‐18 was slightly better than that of OWT‐6 because of the longer withering time and more thorough substance transformation. Conclusion: In conclusion, the formation of honey flavor in beauty tea may be closely related to the DEGs and DMs in these three pathways. Our research provides theoretical data support for further revealing the mechanism of quality formation during the withering process of beauty tea. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

α‐Synuclein phosphorylation at serine‐129 (pS129) is a widely used surrogate marker of pathology in Parkinson's disease and other synucleinopathies. However, we recently demonstrated that phosphorylation of S129 is also a physiological activator of synaptic transmission. In a feed‐forward fashion, neuronal activity triggers reversible pS129. Here, we show that Parkinson's disease‐linked missense mutations in SNCA impact activity‐dependent pS129. Under basal conditions, cytosol‐enriched A30P, H50Q, and G51D mutant forms of α‐synuclein exhibit reduced pS129 levels in rat primary cortical neurons. A53T pS129 levels are similar to wild‐type, and E46K pS129 levels are higher. A30P and E46K mutants show impaired reversibility of pS129 after stimulation. For the engineered profoundly membrane‐associated α‐synuclein mutant "3K" (E35K + E46K + E61K), de‐phosphorylation was virtually absent after blocking stimulation, implying that reversible pS129 is severely compromised. Importantly, pS129 excess resulting from proteasome inhibition is also associated with reduced reversibility by neuronal inhibition, kinase inhibition, or phosphatase activation. Our findings suggest that perturbed pS129 dynamics are probably a shared characteristic of pathology‐associated α‐synuclein, with possible implications for synucleinopathy treatment and diagnosis. Synopsis: Perturbed phospho‐S129 dynamics are a shared characteristic of various models of α‐synuclein dyshomeostasis, with possible implications for synucleinopathy treatment and diagnosis.α‐Synuclein solubility and pS129 accumulation are inversely proportional.α‐Synuclein dyshomeostasis impairs the reversibility of polo‐like‐kinase 2 (Plk2)‐ and protein phosphatase 2A (PP2A)‐modulated activity‐dependent pS129.Impaired pS129 reversibility is likely to be an early pathological change that precedes α‐synuclein aggregation. [ABSTRACT FROM AUTHOR]

Creating security materials that carry distinct information with numerous optical characteristics enables enhanced anticounterfeiting levels to deter forgery ranging from currencies to pharmaceuticals. Circularly polarized long afterglow (CPLA) has attracted extensive attention in anticounterfeiting owing to its multiple and unusual optical properties (i.e., long afterglow and circular polarization), introducing intensity variation into the time dimension. However, constructing a visualized CPLA—meeting the requirements toward practical applications—is still a challenge. Here, a cementation‐coupling strategy is designed to combine chiral photonic membranes with phosphor films for building full‐colored CPLA architectures. The CPLA systems achieve desired performance with a largest afterglow dissymmetry value (gCPLA) of −0.67 and a longest visualization time (tvis) of 40 min simultaneously, satisfying practical demands for information security. As‐prepared CPLA materials are further patterned to work as optical labels in security fields. The resulting multidimensional variations in both time and intensity increase the complexity of information encryption, offering potentials for advanced security technologies. [ABSTRACT FROM AUTHOR]

Cryptocaryon irritans is one of the most harmful marine parasites in mariculture. Copper sulphate is often used to kill parasites and the influence of copper sulphate on the tomont stage of C. irritans was explored in this study. The results showed that excystment rate was not significantly affected when tomonts were exposed to 5 mg/L (76.7%) and 10 mg/L (78.9%) of copper sulphate for 3 h. However, excystment rate was significantly inhibited when exposed to 15 mg/L (33.3%) for 3 h and 5 mg/L (28.9%), 10 mg/L (33.3%) and 15 mg/L (33.3%) for 6 h. After treatment with high concentrations of copper sulphate, the interior of the tomonts was fuzzy under the microscope, and the division process could not be observed. Metabolomic results combined with preliminary transcriptome analysis results showed that the tomonts were induced to produce linoleate, riboflavin, inositol and other substances under the stress of Cu2+, which affected the antioxidant mechanism of the body. Using MDA content determination and antioxidant enzyme activity analysis, copper sulphate was found to cause oxidative damage to tomonts by affecting the generation of metabolites, leading to the death of tomonts. [ABSTRACT FROM AUTHOR]

Apis laboriosa is the largest honeybee that lives mainly on cliff faces, with strong migratory ability. In this study, we firstly sequenced and assembled two complete mitochondrial genomes of A. laboriosa isolated from two distant locations in China (Chongqing and Shangri‐La regions). Combined with the published mitochondrial genome of A. laboriosa from Nepal, comparative genomic analyses were conducted to gain insight into the genetic diversity of giant honeybees from different geographical distributions. The mitochondrial genomes of A. laboriosa from Chongqing and Shangri‐La regions were 15,579 and 15,683 bp in length, respectively, both larger than that from Nepal with the length of 15,510 bp. Three mitochondrial genomes all harbor 37 common genes and present the same AT bias and the frequency of codon usage. However, the fragments including COX1, SSUrRNA, LSUrRNA, and the AT‐rich region of the mitochondrial genome from Shangri‐La region demonstrate distinctive insertions and deletions compared to those from Chongqing and Nepal regions. Phylogenetic trees of mitochondrial genomes show that A. laboriosa from Chongqing is most closely related to that from Nepal, rather than to Shangri‐La. Genetic distance between Shangri‐La and Chongqing or Nepal was even larger than that between the various subspecies of Apis mellifera. Overall, these results unmark that A. laboriosa in different geographical distributions can exhibit high genetic diversity at the mitochondrial genomic level, and therein, A. laboriosa from Shangri‐La may be the subspecies. All these studies will contribute to our understanding of the geographical distribution and genetic differentiation of black giant honeybee in Asian region. [ABSTRACT FROM AUTHOR]

Automatic cervical cancer segmentation in multimodal magnetic resonance imaging (MRI) is essential because tumor location and delineation can support patients' diagnosis and treatment planning. To meet this clinical demand, we present an encoder–decoder deep learning architecture which employs an EfficientNet encoder in the UNet++ architecture (E‐UNet++). EfficientNet helps in effectively encoding multiscale image features. The nested decoders with skip connections aggregate multiscale features from low‐level to high‐level, which helps in detecting fine‐grained details. A cohort of 228 cervical cancer patients with multimodal MRI sequences, including T2‐weighted imaging, diffusion‐weighted imaging, apparent diffusion coefficient imaging, contrast enhancement T1‐weighted imaging, and dynamic contrast‐enhanced imaging (DCE), has been explored. Evaluations are performed by considering either single or multimodal MRI with standard segmentation quantitative metrics: dice similarity coefficient (DSC), intersection over union (IOU), and 95% Hausdorff distance (HD). Our results show that the E‐UNet++ model can achieve DSC values of 0.681–0.786, IOU values of 0.558–0.678, and 95% HD values of 3.779–7.411 pixels in different single sequences. Meanwhile, it provides DSC values of 0.644 and 0.687 on three DCE subsequences and all MRI sequences together. Our designed model is superior to other comparative models, which shows the potential to be used as an artificial intelligence tool for cervical cancer segmentation in multimodal MRI. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lipids are one of the most important bioactive compounds, affecting the character and quality of tea. However, the contribution of lipids to tea productions is still elusive. Here, we systematically identified the lipid profiles of green, oolong, and black teas in purple‐leaf tea (Jinmingzao, JMZ) and green‐leaf tea (Huangdan, HD), respectively. RESULTS: The lipids analysis showed regular accumulation in tea products with different manufacturing processes, among which the fatty acids, glycerolipids, glycerophospholipids, and sphingolipids contribute to the quality characteristics of tea products, including typical fatty acyl (FA), monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerols (DGDG), and phosphatidylcholine (PC). Compared tea materials with products, levels of fatty acids were up‐regulated, while glycerolipids and glycerophospholipids were down‐regulated in tea products. FA 18:3, FA 16:0, MGDG 36:6, DGDG 36:6, PC 34:3, and PC 36:6 were the negative contributors to green tea flavor formation of purple‐leaf tea. The pathway analysis of significant lipids in materials and products of purple‐leaf tea were enriched linolenic acid metabolism pathway and glycerolipid metabolism. CONCLUSION: This study provides insights into the lipid metabolism profiles of different tea leaf colors, and found that fatty acids are essential precursors of black tea flavor formation. © 2021 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Introduction: Evidence strongly suggests that soluble oligomers of amyloid beta protein (oAβ) help initiate the pathogenic cascade of Alzheimer's disease (AD). To date, there have been no validated assays specific for detecting and quantifying oAβ in human blood. Methods: We developed an ultrasensitive oAβ immunoassay using a novel capture antibody (71A1) with N‐terminal antibody 3D6 for detection that specifically quantifies soluble oAβ in the human brain, cerebrospinal fluid (CSF), and plasma. Results: Two new antibodies (71A1; 1G5) are oAβ‐selective, label Aβ plaques in non‐fixed AD brain sections, and potently neutralize the synaptotoxicity of AD brain‐derived oAβ. The 71A1/3D6 assay showed excellent dilution linearity in CSF and plasma without matrix effects, good spike recovery, and specific immunodepletion. Discussion: We have created a sensitive, high throughput, and inexpensive method to quantify synaptotoxic oAβ in human plasma for analyzing large cohorts of aged and AD subjects to assess the dynamics of this key pathogenic species and response to therapy. [ABSTRACT FROM AUTHOR]

Safe and harmless treatment of electrolyte is a critical environment issue for spent lithium‐ion battery recycling; the effective separation of cathode materials from aluminum foil is a key technology for resource utilization. Previous studies have never considered the two as a whole. This study introduced supercritical CO2 technology to realize the integrated treatment of electrolyte removal and cathode material exfoliation. The results indicated that the optimum parameter was obtained at a temperature of 38 °C, a time of 15 min and a pressure of 10 MPa. The peeling efficiency of cathode material from Al foil reached 98.86 wt.%. Mechanism analysis confirmed that the separation of Al foil and cathode material was the result of the weakened adhesion of electrode interface, which can be attributed to the removal of the organic component including carbonate‐based organic solution and organic binder caused by the fluid extraction process. [ABSTRACT FROM AUTHOR]

Regeneration of cathode materials from spent lithium‐ion batteries (LIBs), as an efficient short‐range recycling strategy, is gradually becoming a research hotspot. However, due to the unavoidable influence of impurities in the recycling process, the regenerated material suffers from severe performance degradation during the recycling process. Surface coating is an effective routine to improve cycling stability. Here, regenerated Li(Ni0.8Co0.1Mn0.1)O2 cathode material is successfully wet‐coated by an appropriate amount of MoO3. The study finds the material loading 2.0 wt% MoO3 exhibits even better properties. After 100 cycles, the capacity retention efficiency is significantly improved from 70 % to 86.5 % in the range of 2.8∼4.3 V. It is confirmed that the MoO3 coating effectively stabilized the cathode/electrolyte interface, thus reducing the occurrence of side reactions and improving the electrochemical stability of the battery. In addition, the MoO3 had great electrical conductivity, keeping the lithium diffusion even at a stable level upon cycling. To sum up, our work provides a simple and available modification strategy for nickel‐rich cathode materials recovered from spent LIBs. [ABSTRACT FROM AUTHOR]

The [AuxAg16‐x(SAdm)8(Dppe)2] nanocluster with aggregation‐induced emission (AIE) was synthesized from a non‐fluorescent [Au9Ag12(SAdm)4(Dppm)6Cl6](SbF6)3 nanocluster via a ligand‐exchange engineering (Dppe=1,2‐Bis(diphenylphosphino)ethane, Dppm=Bis(diphenylphosphino)methane, HSAdm=1‐Adamantanethiol). The nanocluster has a Au‐doped icosahedral AuxAg13‐x core, capped by two Ag(SR)3, one Ag(SR)2 and two Dppe ligands. By changing the achiral Dppe ligand into a chiral dbpb ligand ((2S,3S)‐(‐)‐Bis(diphenylphosphino)butane or (2R,3R)‐(+)‐2,3‐Bis(diphenylphosphino)butane), chiral nanoclusters are obtained. ESI‐MS and UV‐vis spectroscopy were performed to track the reaction. This work provides guidance for the construction of new clusters by etching clusters with multidentate phosphine ligands. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is the main subtype of primary lung cancer and is a leading cause of cancer‐related death worldwide. PIWI‐interacting RNAs (piRNAs) are a type of small non‐coding RNAs that may play crucial roles in cancer progression and serve as biomarkers for tumor detection. This study aimed to explore the expression profiles and diagnostic values of piRNAs in LUAD. Methods: Small RNA sequencing was performed to investigate tissue piRNA profiles of LUAD. The expression of selected upregulated piRNAs were detected in tissues and serum exosome samples by quantitative real‐time polymerase chain reaction (qRT‐PCR). Serum exosomes were identified by transmission electron microscope, nanoparticle tracking analysis, and western blot analysis. Receiver operating characteristic (ROC) curve was adopted to quantify the diagnostic potentials of piRNAs in LUAD. Finally, a piRNA panel was developed by multivariate logistic regression model. Results: We identified that 76 piRNAs were overexpressed and 9 piRNAs were underexpressed in LUAD tissues compared with adjacent non‐tumor tissues. Among the top 10 overexpressed piRNAs, 4 piRNAs (piR‐hsa‐26925, piR‐hsa‐5444, piR‐hsa‐30636, and piR‐hsa‐8757) were verified by qRT‐PCR to be significantly upregulated in LUAD tissues. Moreover, piR‐hsa‐26925 and piR‐hsa‐5444 had a significantly higher level in serum exosome samples of LUAD patients than those of healthy controls. We finally established a 2‐piRNA panel composed of piR‐hsa‐26925 and piR‐hsa‐5444, which showed higher diagnostic performance for LUAD with an AUC of 0.833. Conclusions: Our finding revealed the abnormally expressed piRNAs in LUAD, and serum exosomal piR‐hsa‐26925 and piR‐hsa‐5444 could serve as potential biomarkers for LUAD diagnosis. [ABSTRACT FROM AUTHOR]

Ultrasmall nanoclusters are emerging nanocatalysts due to their distinct physico‐chemical properties. However, the instability and agglomeration of these nanoclusters restrict their practical application. Herein, we designed a negatively charged cross‐linked polystyrene (PS) microsphere as support and decorated it with positively charged ultrasmall [Au4Cu5(Dppm)2(C6H11S)6]+[BPh4]− (Au4Cu5, in which Dppm stands for bis‐(diphenylphosphino)methane) nanoclusters through strong electrostatic adsorption, as evidenced by X‐ray photoelectron spectroscopy. The PS@Au4Cu5 nanocomposites were well‐dispersed in water, exhibiting enhanced catalytic activity for the reduction reaction of 4‐nitrophenol to produce 4‐aminophenol. These findings open promising opportunities for supported nanocluster catalysis. [ABSTRACT FROM AUTHOR]

Rationale: Neutrophils constitute massive cellular constituents in inflammatory human gastric cancer (GC) tissues, but their roles in pathogenesis of inflammatory T helper (Th) subsets are still unknown. Methods: Flow cytometry analysis and immunohistochemistry were used to analyze the responses and phenotypes of neutrophils in different samples from 51 patients with GC. Kaplan‐Meier plots and Multivariate analysis for the survival of patients were used by log‐rank tests and Cox proportional hazards models. Neutrophils and CD4+ T cells were purified and cultured for ex vivo, in vitro and in vivo regulation and function assays. Results: GC patients exhibited increased tumoral neutrophil infiltration with GC progression and poor patient prognosis. Intratumoral neutrophils accumulated in GC tumors via CXCL6/CXCL8‐CXCR1‐mediated chemotaxis, and expressed activated molecule CD54 and co‐signaling molecule B7‐H2. Neutrophils induced by tumors strongly expressed CD54 and B7‐H2 in both dose‐ and time‐dependent manners, and a close correlation was obtained between the expressions of CD54 and B7‐H2 on intratumoral neutrophils. Tumor‐derived tumor necrosis factor‐α (TNF‐α) promoted neutrophil activation and neutrophil B7‐H2 expression through ERK‐NF‐κB pathway, and a significant correlation was found between the levels of TNF‐α and CD54+ or B7‐H2+ neutrophils in tumor tissues. Tumor‐infiltrating and tumor‐conditioned neutrophils effectively induced IL‐17A‐producing Th subset polarization through a B7‐H2‐dependent manner ex vivo and these polarized IL‐17A‐producing Th cells exerted protumorigenic roles by promoting GC tumor cell proliferation via inflammatory molecule IL‐17A in vitro, which promoted the progression of human GC in vivo; these effects could be reversed when IL‐17A is blocked. Moreover, increased B7‐H2+ neutrophils and IL‐17A in tumors were closely related to advanced GC progression and predicted poor patient survival. Conclusion: We illuminate novel underlying mechanisms that TNF‐α‐activated neutrophils link B7‐H2 to protumorigenic IL‐17A‐producing Th subset polarization in human GC. Blocking this pathological TNF‐α‐B7‐H2‐IL‐17A pathway may be useful therapeutic strategies for treating GC. [ABSTRACT FROM AUTHOR]

Genomes of single- and double-petal jasmines (Jasminum sambac) provide insights into their divergence time and structural variations LAI scores for SP and DP jasmine genomes were estimated to be ~28.16 and ~24.35, respectively (Figure 1e), which are much higher than that of the recently published MP jasmine genome using nanopore data (Xu I et al i ., 2021). Keywords: Jasminum sambac; genome assembly; divergence time; structural variation EN Jasminum sambac genome assembly divergence time structural variation 1232 1234 3 07/01/22 20220701 NES 220701 Jasmine I Jasminum sambac i (L.) Aiton belongs to the genus I Jasminum i of the Oleaceae family. [Extracted from the article]

Antibody‐dependent cellular cytotoxicity (ADCC) is the primary mechanism of actions for several marketed therapeutic antibodies (mAbs) and for many more in clinical trials. The ADCC efficacy is highly dependent on the ability of therapeutic mAbs to recruit effector cells such as natural killer cells, which induce the apoptosis of targeted cells. The recruitment of effector cells by mAbs is negatively affected by fucose modification of N‐Glycans on the Fc; thus, utilization of afucosylated mAbs has been a trend for enhanced ADCC therapeutics. Most of afucosylated mAbs in clinical or commercial manufacturing were produced from Fut8−/− Chinese hamster ovary cells (CHO) host cells, generally generating low yields compared to wildtype CHO host. This study details the generation and characterization of two engineered CHOZN® cell lines, in which the enzyme involved in guanosine diphosphate (GDP)‐fucose synthesis, GDP mannose‐4,6‐dehydratase (Gmds) and GDP‐L‐fucose synthase (FX), was knocked out. The top host cell lines for each of the knockouts, FX−/− and Gmds−/−, were selected based on growth robustness, bulk MSX selection tolerance, production titer, fucosylation level, and cell stability. We tested the production of two proprietary IgG1 mAbs in the engineered host cells, and found that the titers were comparable to CHOZN® cells. The mAbs generated from either KO cell line exhibited loss of fucose modification, leading to significantly boosted FcγRIIIa binding and ADCC effects. Our data demonstrated that both FX−/− and Gmds−/− host cells could replace Fut8−/− CHO cells for clinical manufacturing of antibody therapeutics. [ABSTRACT FROM AUTHOR]

Objectives: Mechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus and transfer it into biological signals, and thereby promote alveolar bone remodelling, is unclear. Materials and Methods: An animal model of force‐induced tooth movement and a compressive force in vitro was used. After force application, tooth movement distance, mesenchymal stem cell and osteoclast number, and proinflammatory cytokine expression were detected in periodontal tissues. Then, rat primary PDLSCs with or without force loading were isolated, and their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation and immunoregulatory properties were evaluated. Under compressive force in vitro, the effects of the ERK signalling pathway on PDLSC characteristics were evaluated by Western blotting. Results: Mechanical force in vivo induced PDLSC proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation; the force‐stimulated PDLSCs showed greater clonogenicity and proliferation, reduced differentiation ability, improved induction of macrophage migration, osteoclast differentiation and proinflammatory factor expression. The biological changes induced by mechanical force could be partially suppressed by TRPV4 inhibition. Mechanistically, force‐induced activation of TRPV4 in PDLSCs regulated osteoclast differentiation by affecting the RANKL/OPG system via ERK signalling. Conclusions: Taken together, we show here that TRPV4 activation in PDLSCs under mechanical force contributes to changing their stem cell characteristics and modulates bone remodelling during tooth movement. [ABSTRACT FROM AUTHOR]

Tuning the electron transport at the molecular scale is a key step in realizing functional electronic components for molecular electronics, and ongoing interest aims at achieving a higher modulation ratio for single‐molecular transistors. Here, a feasible strategy that connects the redox‐active moieties with conjugated chains is proposed to improve the electrochemical gating efficiency of molecular junctions in ionic liquid. Benefiting from the low energy barrier height between the Fermi level of the electrode and the frontier molecular orbitals, the conductance of C=C−Fc−Py is about one order of magnitude larger and the conductance on/off ratio shows 160 % improvement compared to that of C−C−Fc−Py at the equilibrium potential of Fc+/Fc. This work provides a new way to design high‐performance molecular devices. [ABSTRACT FROM AUTHOR]

The high‐dimensional (that is, three‐dimensional (3D)) assembly of nanomaterials is an effective means of improving their properties; however, achieving this assembly at the atomic level remains challenging. Herein, we obtained a novel nanocluster, [Au8Ag57(Dppp)4(C6H11S)32Cl2]Cl (Dppp=1,3‐bis(diphenylphosphino)propane) showing a 3D octameric assembly mode involving the kernel penetration of eight complete icosahedral Au@Ag10Au2 units for the first time. The atomically precise structure was determined by single‐crystal X‐ray diffraction, and further confirmed by thermogravimetric analysis, X‐ray photoelectron spectroscopy, and electrospray ionization mass spectrometry measurements. Furthermore, ligand‐induced transformation prompted the conversion of [Au8Ag57(Dppp)4(C6H11S)32Cl2]Cl, with complete octameric fusion into [Au8Ag55(Dppp)4(C6H11S)34][BPh4]2, with incomplete octameric fusion. These observations will hopefully facilitate further research on the assembly of M13 nanobuilding blocks. [ABSTRACT FROM AUTHOR]

An atomically precise luminescent Pt‐Ag alloy nanocluster (Pt1Ag9[P(Ph‐F)3]7Cl3 (P(Ph‐F)3= tris(4‐fluorophenyl) phosphine)) (Pt1Ag9 for short) was synthesized. Its structure was determined by single‐crystal X‐ray diffraction (SCXRD) and further confirmed by electrospray ionization mass spectrometry (ESI‐MS), X‐ray photoelectron spectrospray (XPS) and Nuclear Magnetic Resonance (NMR) measurements. Surprisingly, the Pt1Ag9 kernel can be regarded as the icosahedral Pt1Ag12 kernel missing three Ag atoms, accompanied with no structural reformation in this nanocluster. And the central Pt atom was exposed and capped by phosphine ligand directly in contrast with other reported Pt‐Ag alloy nanoclusters. Upon excitation at 435 nm, the emission spectra of Pt1Ag9 nanocluster exhibits a prominent peak at 662 nm (quantum yield QY = 0.6658 %) with a very short photoluminescence lifetime (0.357 ns). This work provides a deep understanding of the structure and properties of Pt‐Ag alloy nanoclusters. [ABSTRACT FROM AUTHOR]

This study aimed to explore the biological role and molecular mechanism of long noncoding RNA (lncRNA) rhabdomyosarcoma 2‐associated transcript (RMST) in regulating microglial activation. Mouse microglial BV2 cells were cultured to establish the cell model of cerebral ischemic stroke by oxygen–glucose deprivation (OGD). We observed highly expressed RMST, increased expression of M1, and decreased expression of M2 markers in BV2 microglial cells stimulated with OGD. These alterations were reversed by RMST knockdown. Activation of transforming growth factor‐beta‐activated kinase 1 (TAK1)‐mediated nuclear factor‐κB (NF‐κB) pathway was observed upon OGD stimulation, which was promoted by RMST through competitively binding with heterogeneous nuclear ribonucleoprotein K (hnRNPK), confirmed by RNA pull down and RNA immunoprecipitation (RIP) assays. Furthermore, RMST overexpressing‐BV2 cells effectively enhanced neuronal apoptosis. In conclusion, RMST promoted OGD‐induced microglial M1 polarization by competitively interacting with hnRNPK via TAK1‐mediated NF‐κB pathway, which will provide a basis for understanding the pathogenesis of cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

Metal superatomic nanoclusters, with electronic structures similar to those of one certain atom, are an important type of metal clusters. Interestingly, metal clusters with metal cores composed of either icosahedral M13 or icosahedral assemblies always have a greater potential to become superatomic clusters. Furthermore, superatomic clusters with similar electronic compositions could possess various geometric structures, owing to differences in the shells; this provides a deeper understanding of the metal superatomic cluster and the assembly for nanomaterials. Therefore, this review focuses on the geometric and electronic structures of gold/silver superatomic clusters based on icosahedron M13 units and their alloys, which will facilitate the development of various applications of superatomic clusters. [ABSTRACT FROM AUTHOR]

An enantioselective addition of enamides to cyclic ketimines generated in situ from 3‐hydroxyisoindolin‐1‐ones was developed. This reaction takes advantage of readily available substrates, mild reaction conditions, as well as enlarged reaction generality, affording chiral 3,3‐disubstituted isoindolin‐1‐ones with a quaternary stereogenic center in high yields (up to 98%) and enantioselectivities (up to 99% ee). [ABSTRACT FROM AUTHOR]

Isoalantolactone (IATL), a sesquiterpene lactone compound, possesses many pharmacological and biological activities, but its role in glioblastoma (GBM) treatment is still unknown. The aim of the current study was to investigate the antiglioma effects of IATL and to explore the underlying molecular mechanisms. In the current study, the biological functions of IATL were examined by MTT, cell migration, colony formation, and cell apoptosis assays. Confocal immunofluorescence techniques, chromatin immunoprecipitation, and pull‐down assays were used to explore the precise underlying molecular mechanisms. To examine IATL activity and the molecular mechanisms by which it inhibits glioma growth in vivo, we used a xenograft tumor mouse model. Furthermore, Western blotting was used to confirm the changes in protein expression after IATL treatment. According to the results, IATL inhibited IKKβ phosphorylation, thus inhibiting both the binding of NF‐κB to the cyclooxygenase 2 (COX‐2) promoter and the recruitment of p300 and eventually inhibiting COX‐2 expression. In addition, IATL induced glioma cell apoptosis by promoting the conversion of F‐actin to G‐actin, which in turn activates the cytochrome c (Cyt c) and caspase‐dependent apoptotic pathways. In the animal experiments, IATL reduced the size and weight of glioma tumors in xenograft mice and inhibited the expression of COX‐2 and phosphorylated NF‐κB p65 in the transplanted tumors. In conclusion, the current study indicated that IATL inhibited the expression of COX‐2 through the NF‐κB signaling pathway and induced the apoptosis of glioma cells by increasing actin transformation. These results suggested that IATL could be greatly effective in GBM treatment. [ABSTRACT FROM AUTHOR]

We report the observation of dimerization of two 8‐electron superatom cluster units in the crystallographic structures of Au2Ag42(SAdm)27(BPh4) and [Au2Ag48(S‐tBu)20(Dppm)6Br11]Br(BPh4)2 nanoclusters. The crystallographic analysis reveals that both nanoclusters have a Au2Ag24 core made of two separated icosahedral without sharing metal atoms, and each icosahedron has an eight‐electron (8e) closed shell (1S21P6). The valence electronic structures of these two nanoclusters are analogous to that of a Ne atom dimer (Ne2) according to the density functional theory (DFT) analysis. This is the first crystallographic observation of the dimerization of 8‐electron superatom units. This study enriches the fundamental knowledge on metal superatom clusters and implies the possibility for further assembling metal superatom building blocks into higher order superatom molecules. [ABSTRACT FROM AUTHOR]

Abstract: Malignant glioma is one of the most challenging central nervous system diseases to treat and has high rates of recurrence and mortality. Current therapies often fail to control tumor progression or improve patient survival. Marinobufagenin (MBG) is an endogenous mammalian cardiotonic steroid involved in sodium pump inhibition. Currently, various studies have indicated the potential of MBG in cancer treatments; however, the precise mechanisms are poorly understood. The functions of MBG were examined using colony formation, migration, cell cycle, and apoptosis assays in glioma cells. A mitochondrial membrane potential assay was performed to determine the mitochondrial transmembrane potential change, and cytochrome c release from mitochondria was assayed by fluorescence microscopy. An immunofluorescence assay was performed, and the nuclear translocation of NF‐κB in glioma cells was confirmed by confocal microscopy. Western blotting and RT‐qPCR were used to detect the protein and gene expression levels, respectively. In addition, transfection experiment of ATP1A1‐siRNA was further carried out to confirm the role of sodium pump α1 subunit in the anticancer effect of MBG in human glioma. The apoptosis‐promoting and anti‐inflammatory effects of MBG were further investigated, and the sodium pump α1 subunit and the ERK signaling pathway were found to be involved in the anticancer effect of MBG. The in vivo anticancer efficacy of MBG was also tested in xenografts in nude mice. Thus, therapies targeting the ERK signaling‐mediated mitochondrial apoptotic pathways regulated by MBG might represent potential treatments for human glioma, and this study could accelerate the finding of newer therapeutic approaches for malignant glioma treatment. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Macrophage inhibitory cytokine‐1 (MIC‐1), a transforming growth factor‐β superfamily cytokine, is involved in tumor pathogenesis, and its measurement can be used as a clinical tool for the diagnosis of a wide range of cancers. Objectives: The aim of this study was to explore the diagnostic value of serum MIC‐1 in patients with solitary pulmonary nodules (SPNs). Methods: Serum specimens from 158 malignant SPN patients, 110 benign SPN patients, along with 120 healthy volunteers. The levels of serum MIC‐1 were measured by sandwich enzyme‐linked immunosorbent assay. Results: Serum levels of MIC‐1 in malignant SPN patients were significantly higher than those in benign SPN patients (P < .01), or those in healthy volunteers (P < .01). With a cutoff of 685.8 pg/ml, the sensitivity and specificity of MIC‐1 in differentiating between malignant SPN patients and benign SPN patients, and between malignant SPN patients and healthy volunteers was, 56.3% and 92.7%, and 65.8% and 96.7%, respectively. An area under the curve (AUC) for malignant SPN resulting from MIC‐1, which was significantly better than any other tumor markers tested including carbohydrate antigens 12‐5 (CA125), and carcinoembryonic antigen (CEA). Conclusions: In conclusion, measurement of serum MIC‐1 levels could be considered as a diagnostic biomarker for malignant SPN patients. [ABSTRACT FROM AUTHOR]

Abstract: Herein we report the synthesis and structure determination of a non‐fluorescent Au4Ag5(dppm)2(SAdm)6(BPh4) (dppm=bis(diphenylphosphino)methane and HSAdm=1‐adamantane mercaptan) nanocluster in methanol with extremely strong AIE when aggregating to the solid state (i.e., film or crystal). This phenomenon was rarely reported in structural determined noble metal nanoclusters. The extended X‐ray absorption fine structure (EXAFS) measurement ruled out the hypothesis that the luminescence originated from the structure change in different states. Besides, the crystal structure (determined by X‐ray diffraction) revealed that the tightly combined left‐ and right‐handed enantiomers induced the strong restriction of intramolecular motions (RIM), which may have an impact on aggregation‐induced emission. [ABSTRACT FROM AUTHOR]

To review the optimality and safety of different anti-Amyloid-b(Ab) immunotherapies for Alzheimer's disease (AD). Published randomized controlled trials were comprehensively reviewed from electronic databases (Cochrane library, Embase, Pubmed, and Google scholar). Pooled outcomes as mean difference or odds ratio values with 95% confidence interval were reported. The network estimates with confidence and predictive intervals for all pairwise relative effects was evaluated. Optimal intervention was ranked by benefit-risk ratio based on the surface under the cumulative ranking curve. Eleven eligible RCTs from 9 literatures, including 5141 patients and 5 interventions were included. The quality of evidence was rated low in comparisons. For efficacy, in terms of Mini-Mental State Examination, aducanumab and solanezumab are significantly effective than placebo. For safety, in terms of Amyloid-Related Imaging Abnormalities (ARIA), bapineuzumab and aducanumab are significantly worse than placebo. There were no significant differences in outcomes of Alzheimer's disease Assessment Scale-Cognitive subscale, Disability Assessment for Dementia, Adverse Events, and mortality. Given the clinical therapeutic effects of anti-Aγ immunotherapies for AD, aducanumab and solanezumab improve the cognitive function, while aducanumab and bapineuzumab may increase the risks of ARIA. [ABSTRACT FROM AUTHOR]

A series of Sr2P2O7:Dy3+, Sr2P2O7:Ce3+ and Sr2P2O7:Dy3+,Ce3+ phosphors was synthesized via the one-step calcination process for the precursors prepared by co-precipitation methods. The phases, morphology, quantum efficiency and photoluminescence properties of the obtained phosphors were characterized systematically. These results show that the near-spherical particles prepared through calcining the precursors by means of ammonium dibasic phosphate co-precipitation (method 3) have the smallest particle size and strongest emission intensity among the three methods in the paper. With Dy3+ concentration increasing in Sr2P2O7:Dy3+ phosphors, the luminescence intensity first increases, reaches maximum, and then decreases. A similar trend was followed by Sr2P2O7:Ce3+ with Ce3+concentration increasing. A successful attempt was made to initiate the energy transfer mechanism from Ce3+ to Dy3+ in the host lattice and an overlap between the emission band of Ce3+ and the excitation band of Dy3+ indicated that the Ce3+ → Dy3+ energy transfer may indeed exist. It is clear that the photoluminescence intensity of Dy3+ as well as the quantum efficiency of the phosphor can be enhanced markedly by co-doping Ce3+. Sr2P2O7:Dy3+,Ce3+ has its (CIE) chromaticity coordinates in the bluish-white-light region, near the standard illuminant D65. The CIE 1913 chromaticity coordinates of Sr2P2O7:Dy3+ phosphors fall in the white-light region, and are adjacent to the ideal white-light coordinates. In addition, the colour temperature and colour tone of Sr2P2O7:Dy3+ could be adjusted by changing the relative concentration of Dy3+. In short, Sr2P2O7:Dy3+ can be a promising single-phased white-light emitting phosphor for near-UV (NUV) w-LEDs. [ABSTRACT FROM AUTHOR]

An homologous series of divinylchalcogenophene-bridged binuclear ruthenium complexes [{(PMe3)3Cl(CO)Ru}2-(μ-CH=CH-C4H2E-CH=CH)] (4a-4d, E = O, S, Se, Te) have been synthesised and fully characterised by X-ray crystallography and various spectroscopic techniques. The single-crystal X-ray diffraction results reveal a distinct short/long bond-length alternation along the polyene-like hydrocarbon backbone, with geometric constraints imposed by the chalcogenophene leading to an increasing distance between the two metal centres (dRu-Ru) in complexes 4a-4d as the heteroatom in the five-membered ring is changed from oxygen (9.980 Å in 4a) to tellurium (11.063 Å in 4d). The complexes undergo two sequential one-electron oxidation processes, the half-wave potential and separation of which appear to be sensitive to a range of factors, including aromatic stabilisation and re-organisation energies. Analysis of [4a-4d]n+ (n = 0, 1, 2) by UV/Vis/NIR and IR spectro-electrochemical methods, supported by DFT calculations (n = 0, 1), revealed that the redox character of the complexes is dominated by the polyene-like backbone with the chalcogenide playing a subtle but influential, structural rather than electronic, role. In the radical cations [4a-4d]+, the charge is rather effectively delocalised over the 10-atom Ru--[4-s-cis-all-trans-(CH=CH)4]--Ru chain, giving rise to a species with spectroscopic properties not dissimilar to oxidised polyaceylene. [ABSTRACT FROM AUTHOR]

In order to improve the luminescent performance of silicate blue phosphors, Sr(1.5- x)-(1.5 y)Mg0.5SiO4: xEu2+, yCe3+ phosphors were synthesized using one-step calcination of a precursor prepared by chemical co-precipitation. The crystal structure and luminescent properties of the phosphors were analyzed using X-ray diffraction and fluorescence spectrophotometry, respectively. Because the activated ions (Eu2+) can occupy two different types of sites (Sr1 and Sr2), the emission spectrum of Eu2+ excited at 350 nm contains two single bands (EM1 and EM2) in the wavelength range 400-550 nm, centered at 463 nm, and the emission intensity first increases and then decreases with increasing concentrations of Eu2+ ions. Co-doping of Ce3+ ions can greatly enhance the emission intensity of Eu2+ by transferring its excitation energy to Eu2+. Because of concentration quenching, a higher substitution concentration of Ce3+ can lead to a decrease in the intensity. Meanwhile, the quantum efficiency of the phosphor is improved after doping with Ce3+, and a blue shift phenomenon is observed in the CIE chromaticity diagram. The results indicate that Sr(1.5- x)-(1.5 y)Mg0.5SiO4: xEu2+, yCe3+ can be used as a potential new blue phosphor for white light-emitting diodes. [ABSTRACT FROM AUTHOR]

A phase-transfer-catalyzed asymmetric Michael addition of (iminomethyl)phosphonates to α,β-unsaturated ketones is described. In the presence of 1 mol-% of a chiral dinuclear N-spiro ammonium salt, the addition reaction proceeded smoothly to afford the adducts in up to 97 % yield with up to 99:1 dr and 78 % ee. One of the products was readily converted into a cyclic α-aminophosphonic acid derivative without any erosion of the enantiopurity. [ABSTRACT FROM AUTHOR]