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Advanced breast cancer with recurrent and distal organ metastasis is aggressive and incurable. The current existing treatment strategies for advanced breast cancer are difficult to achieve synergistic treatment of recurrent tumors and distant metastasis, resulting in poor clinical outcomes. Herein, a synergistic therapy strategy composed of biomimetic tumor‐derived exosomes (TEX)‐Liposome‐paclitaxel (PTX) with lung homing properties and gold nanorods (GNR)‐PEG, was designed, respectively. GNR‐PEG, with well biocompatibility, cured recurrent tumors effectively by thermal ablation under the in situ NIR irradiation. Meanwhile, GNR‐mediated thermal ablation activated the adaptive antitumor immune response, significantly increased the level of CD8+ T cells in lungs and the concentration of serum cytokines (tumor necrosis factor‐α, interlekin‐6, and interferon‐γ). Subsequently, TEX‐Liposome‐PTX preferentially accumulated in lung tissues due to autologous tumor‐derived TEX with inherent specific affinity to lung, resulting in a better therapeutic effect on lung metastasis tumors with the assistance of adaptive immunotherapy triggered by GNR in vivo. The enhanced therapeutic efficacy in advanced breast cancer was a combination of thermal ablation, adaptive antitumor immunotherapy, and targeted PTX chemotherapy. Hence, the synergistic strategy based on GNR and TEX‐Liposome provides selectivity to clinical treatment of advanced breast cancer with recurrent and metastasis. [ABSTRACT FROM AUTHOR]

Aim: To investigate the voiding pattern in <4-week-old newborns by 12-h daytime observation periods. Methods: Twenty-one healthy 1- to 28-day-old newborns were included (10 full term, 11 preterm). The 12-h free voiding parameters, including voiding frequency (VF), voiding volume (VV), post-voiding residual volumes (PRV) and status at voiding (awake/sleep), were recorded at day 1, 4, 7, 14 and 28 after birth. Results: Voiding was recorded 778 times. VF increased in the full-term and preterm newborns between day 4 and 7, decreased in preterms between day 14 and 28, but remained higher than in the full terms. VV increased twice in full terms and once in preterms during 28 days and PRV fluctuated. In contrast, VV was higher in the full term than in the preterms at days 4, 7, 14 and 28. PRV was higher at days 4 and 28. Interrupted voiding was less frequent in the full term than in the preterms. Conclusion: Voiding pattern in the preterms differed in many ways from that of the full-term newborns. Frequent interrupted and incomplete voiding pattern in the preterm newborns indicates a disrupted coordination of the detrusor-sphincter and a delayed maturation of the neural micturition centre. [ABSTRACT FROM AUTHOR]

Climatic oscillations during the last few million years had well-documented effects on the distributions and genomes of temperate plants and animals, but much less is known of their impacts on tropical and subtropical species. In contrast to Europe and North America, ice-sheets did not cover most of China during glacial periods, and the effects of glacial cycles were less dramatic. Fig trees are a predominantly tropical group pollinated by host-specific fig wasps. We employed partial mitochondrial COI (918 bp) and nuclear ITS2 (462 bp) gene sequences to investigate the genetic structure and demographic histories of the wasps that pollinate the subtropical Ficus pumila var. pumila in Southeastern China. Deep genetic divergence in both mitochondrial (7.2-11.6%) and nuclear genes (1.6-2.9%) indicates that three pollinator species are present and that they diverged about 4.72 and 6.00 Myr bp. This predates the Quaternary ice ages, but corresponds with the formation of the Taiwan Strait and uplifting of the Wuyi-Xianxia Mountains. The three pollinators have largely allopatric distribution patterns in China and display different postglacial demographic histories. Wiebesia spp. 1 and 2 occupy, respectively, the northern and southern regions of the mainland host range. Their populations both underwent significant postglacial spatial expansions, but at different times and at different rates. Wiebesia sp. 3 is largely restricted to northern islands and shows less evidence of recent population expansion. Their mainly allopatric distributions and different demographic histories are consistent with host plant postglacial expansion from three distinct refugia and suggest one mechanism whereby fig trees gain multiple pollinators. [ABSTRACT FROM AUTHOR]

ABSTRACT. As it is extremely difficult to make DNA transformation for the obligate fungus, Blumeria graminis f. sp. tritici ( Bgt), we developed a heterologous expression system for characterization of a Bgt gene, CYP51, which encodes 14α-demethylase. The CYP51 gene from Bgt was transformed into the necrotrophic fungus, Botrytis cinerea. Reverse transcription polymerase chain reaction showed that the Bgt CYP51 was transcribed in B. cinerea. Green fluorescence was observed in the transformants of B. cinerea carrying the Bgt CYP51-GFP fusion cassette, suggesting that its translation was successful. Fungicide sensitivity tests revealed that B. cinerea transformed with Bgt CYP51 showed reduced sensitivity to a sterol demethylation inhibitor triadimefon, but not to a benzimidazole fungicide carbendazim. These results indicated that this heterologous expression system can be used for functional analysis of other Bgt genes. [ABSTRACT FROM AUTHOR]

The synthesis of glycoside-based trisiloxane surfactants of the general formula MeSiOSiMeROSiMe (R = (CH)(OCHCH)OR, R = glycosyl) is described, and the surface activity properties of the surfactant are studied. Diethylene glycol monoallyl ether glycoside is synthesized by reacting the diethylene glycol monoallyl ether with glucose. The glycoside-based trisiloxane surfactant is prepared by hydrosilylation of the precursor glycoside with hydrogen-containing trisiloxane. The product is structurally characterized by IR, H NMR and MS. The surface tension of an aqueous solution is reduced to approximately 20 mN m at concentration level of 10 mol L. [ABSTRACT FROM AUTHOR]

The latent TGF-β binding proteins (LTBP-1 -3, and -4) assist in the secretion and localization of latent TGF-β molecules. Ltbp3and Ltbp4S mice have distinct phenotypes and only in the lungs does deficiency of either Ltbp-3 or Ltbp-4 cause developmental abnormalities. To determine if these two LTBPs have additional common functions, we generated mice deficient for both Ltbp-3 and Ltbp-4S. The only novel defect in Ltbp3; Ltbp4S mice was an early lethality compared to mice with single mutations. In addition lung abnormalities were exacerbated and the terminal air sac septation defect was more severe in Ltbp3; Ltbp4S mice than in Ltbp4S mice. Decreased cellularity of Ltbp3; Ltbp4S lungs was correlated with higher rate of apoptosis in newborn lungs of Ltbp3; Ltbp4S animals compared to WT, Ltbp3, and Ltbp4S mice. No differences in the maturation of the major lung cell types were discerned between the single and double mutant mice. However, the distribution of type 2 cells and myofibroblasts was abnormal, and myofibroblast segregation in some areas might be an indication of early fibrosis. We also observed differences in ECM composition between Ltbp3; Ltbp4S and Ltbp4S lungs after birth, reflected in decreased incorporation of fibrillin-1 and -2 in Ltbp3; Ltbp4S matrix. The function of the lungs of Ltbp3; Ltbp4S mice after the first week of life was potentially further compromised by macrophage infiltration, as proteases secreted from macrophages might exacerbate developmental emphysema. Together these data indicate that LTBP-3 and -4 perform partially overlapping functions only in the lungs. J. Cell. Physiol. 226: 1499-1509, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Genetic network programming (GNP) is an evolutionary algorithm which represents its solutions by means of graph structures. Since GNP can create quite compact programs and has an implicit memory function, it works especially well in dynamic environments. In addition, a study of the creation of trading rules on stock markets using GNP with Importance Index (GNP-IMX) has been made. The IMX is one of the criteria for decision making. However, the values of the IMXs must be determined by experience and knowledge. Therefore, in this paper, IMXs are adjusted appropriately during stock trading in order to predict the rise and fall of the stocks. In addition, newly defined flag nodes are introduced into GNP, which makes it possible to appropriately judge the current situation of the stock prices, and also contributes to the use of many kinds of nodes in the GNP program. In a simulation, programs were evolved using the stock prices of 20 companies. Then the generalization ability of the method was tested and compared with GNP without flag nodes, GNP without IMX adjustment, and Buy & Hold. © 2010 Wiley Periodicals, Inc. Electron Comm Jpn, 94(1): 25-33, 2011; Published online in Wiley Online Library (). DOI 10.1002/ecj.10269 [ABSTRACT FROM AUTHOR]

Seven bacteria strains were isolated from fresh uncooked ark shells and were subsequently identified by their unique fatty acid profile using Sherlock Microbial Identification System (MIS). Identification with MIS followed the manufacturer's instruction except for 2.7% NaCl supplement in culture medium because these halophilic bacteria do not grow well on the standard trypticase soy broth agar medium. Results obtained from MIS were verified by 16S rRNA sequence analysis. Based on the sequence of 16S rRNA gene, SB1 was Vibrio alginolyticus, SB3 was Vibrio parahaemolyticus, SB2 was Pseudoalteromonas haloplanktis, AS1 was Vibrio furnissii, TG1 was Vibrio mediterranei, TG2 was Bacillus circulans, and TG3 was Pseudomonas fluorescens. The results obtained from 16S rRNA sequence analysis were consistent with those obtained from MIS. These results suggested that both methods can be applied for routine identification of bacteria isolated from fresh seafood to ensure that the consumption of uncooked ark shells is safe. [ABSTRACT FROM AUTHOR]

Recently, genetic network programming (GNP), an extension of the genetic algorithm (GA) and genetic programming (GP), has been proposed. GNP can make compact programs and can memorize the past history implicitly, because it expresses the solution by directed graphs and therefore can reuse the nodes. In this research, intron-like nodes are introduced for improving the performance of GNP. The aim of introducing intron-like nodes is to use every node as much as possible. It is found from simulations that intron-like nodes are useful for improving the training speed and generalization ability. © 2010 Wiley Periodicals, Inc. Electron Comm Jpn, 93(8): 23–31, 2010; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/ecj.10259 [ABSTRACT FROM AUTHOR]

Bartter's syndrome is a constellation of symptoms characterized by hyper-reninemic hypokalemia, metabolic alkalosis, elevated renin and aldosterone, low or normal blood pressure, and hyperplasia of the juxtaglomerular apparatus. So far, five gene mutations in proteins regulating the sodium chloride transport in the thick ascending limb of Henle's loop have been described. However, the molecular mechanisms underlying the presentation of hypomagnesemia in some of these patients remains unclear. Claudins are a family of transmembranous proteins within the tight junctions that have been shown to be important for the paracellular movement of ions. Mutations in claudin-16 have been identified in patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. To test the hypothesis that mutations in claudin genes may be involved in the altered magnesium and calcium transport in Bartter's syndrome, we began to examine the genes of claudins known to be present in renal tubules in four pediatric patients with Bartter's syndrome. All four patients were African Americans with hypomagnesemia and hypercalciuria. In this study, we did not find any mutation in the coding regions of claudin-2, -3, -4, -7, -8, -10, -11, or -16 genes in these patients. However, all patients had a single nucleotide substitution of C for T at the position of 451 of claudin-8 gene sequence that changes amino acid residue from serine to proline at the position of 151 in the second extracellular domain of claudin-8 protein. The significance of this known single nucleotide polymorphism remains to be determined. [ABSTRACT FROM AUTHOR]

Gambogic acid, the main active compound of gamboge resin of Garcinia hanburryi, has recently exhibited marked antitumour potency on solid tumours of various derivations. We demonstrate here that gambogic acid also present powerful antileukaemic potency through both growth arrest and apoptosis induction in Jurkat cells, which was accompanied by typical apoptotic morphological changes and sharp decreased expression of Bcl-xL and Bcl-2. Furthermore, nucleophosmin, recently demonstrated to be mutated and aberrantly localized in the cytoplasm of leukaemia blasts in a high proportion of patients with acute myeloid leukaemia, was over-expressed in Jurkat cells. As the sole site of nucleocytoplasmic communication, the protein components of nuclear pore complex, such as NUP98, NUP88, NUP214 complex, were also deregulated in Jurkat cells. Especially, NUP98 was found to distribute mainly at the cell membrane, while NUP88 and NUP214 situated not just at the nuclear envelope, but also in the cytoplasm. However, in vitro treatment with gambogic acid resulted in significantly reduced expression of nucleophosmin and all three nucleoporins in a dose-dependent manner. Moreover, most of NUP88 and NUP214 nucleoporins were relocated to the nuclear rim in the gambogic acid-treated cells. These results suggest that the fact that nucleophosmin and some nucleoporins might act as new targets of gambogic acid, correlates well with the sensitivity to gambogic acid, as well as the rate of apoptosis induced by gambogic acid. Mechanisms that regulate nucleocytoplasmic transport of proteins may provide novel opportunities for drug development. [ABSTRACT FROM AUTHOR]

Background and objective: Cyclooxygenase-2 (COX-2) and its product prostaglandin E2 (PGE2) have been demonstrated to play critical roles in inflammation in respiratory diseases. However, the role of COX-2 in airway remodelling in COPD remains to be elucidated. Matrix metalloproteinase-2 (MMP-2) is associated with both inflammation and airway remodelling in COPD. The objective of this study was to measure the expression of COX-2 and the concentrations of PGE2 and MMP-2, and to investigate the role of COX-2 and PGE2 in airflow limitation mediated by MMP-2, in the pathogenesis of COPD. Methods: Forty-three patients with stable COPD, twelve smoking control subjects and ten non-smoking control subjects were enrolled. Induced sputum was obtained for measurement of the concentrations of PGE2 and MMP-2 by ELISA. COX-2 protein expression was assessed by western blotting. Results: PGE2 and MMP-2 concentrations were significantly higher in both smoking control subjects and patients with COPD than in non-smoking control subjects ( P < 0.01). Moreover, the levels of PGE2 and MMP-2 were inversely correlated with FEV1% predicted in COPD patients (PGE2: r = −0.748, P < 0.01; MMP-2: r = −0.801, P < 0.01). Levels of PGE2 were also positively correlated with those of MMP-2 in patients with COPD ( r = 0.775, P < 0.01). Expression of COX-2 protein was significantly higher in COPD patients than in non-smoking control subjects. Conclusions: COX-2 and its product PGE2 are not only involved in airway inflammation, but may also contribute to the severity of airflow limitation mediated by MMP-2 during progression of COPD. [ABSTRACT FROM AUTHOR]

Genetic changes over space and time provide insights into the relative roles of evolutionary factors in shaping genetic patterns within plant populations. However, compared with spatial genetic structure, few studies have been conducted on genetic changes over time. In this study, we used six polymorphic microsatellite loci to assess genetic variation of six size-classes of the population of Liushan, Cryptomeria japonica var. sinensis, in the Tianmushan National Nature Reserve, whose origin was debatable. The mean number of alleles per locus and expected heterozygosity were 4.583 and 0.599 9 respectively, lower than other conifers with the same life history characteristics. FST was 0.002 ± 0.003, and the pairwise test revealed no significant differentiation in any pair of size classes. Significant heterozygosity excesses were detected in five size classes except the oldest one, indicating bottleneck event(s). The above results support the hypothesis that Tianmushan population was introduced and followed by natural regeneration. [ABSTRACT FROM AUTHOR]

Hollow nanoporous carbon architectures (HNCs) present significant utilitarian value for a wide variety of applications. Facile and efficient preparation of HNCs has long been pursued but still remains challenging. Herein, we for the first time demonstrate that single‐component metal–organic frameworks (MOFs) crystals, rather than the widely reported hybrid ones which necessitate tedious operations for preparation, could enable the facile and versatile syntheses of functional HNCs. By controlling the growth kinetics, the MOFs crystals (STU‐1) are readily engineered into different shapes with designated styles of crystalline inhomogeneity. A subsequent one‐step pyrolysis of these MOFs with intraparticle difference can induce a simultaneous self‐hollowing and carbonization process, thereby producing various functional HNCs including yolk‐shell polyhedrons, hollow microspheres, mesoporous architectures, and superstructures. Superior to the existing methods, this synthetic strategy relies only on the complex nature of single‐component MOFs crystals without involving tedious operations like coating, etching, or ligand exchange, making it convenient, efficient, and easy to scale up. An ultra‐stable Na‐ion battery anode is demonstrated by the HNCs with extraordinary cyclability (93 % capacity retention over 8000 cycles), highlighting a high level of functionality of the HNCs. [ABSTRACT FROM AUTHOR]

Hollow nanoporous carbon architectures (HNCs) present significant utilitarian value for a wide variety of applications. Facile and efficient preparation of HNCs has long been pursued but still remains challenging. Herein, we for the first time demonstrate that single‐component metal–organic frameworks (MOFs) crystals, rather than the widely reported hybrid ones which necessitate tedious operations for preparation, could enable the facile and versatile syntheses of functional HNCs. By controlling the growth kinetics, the MOFs crystals (STU‐1) are readily engineered into different shapes with designated styles of crystalline inhomogeneity. A subsequent one‐step pyrolysis of these MOFs with intraparticle difference can induce a simultaneous self‐hollowing and carbonization process, thereby producing various functional HNCs including yolk‐shell polyhedrons, hollow microspheres, mesoporous architectures, and superstructures. Superior to the existing methods, this synthetic strategy relies only on the complex nature of single‐component MOFs crystals without involving tedious operations like coating, etching, or ligand exchange, making it convenient, efficient, and easy to scale up. An ultra‐stable Na‐ion battery anode is demonstrated by the HNCs with extraordinary cyclability (93 % capacity retention over 8000 cycles), highlighting a high level of functionality of the HNCs. [ABSTRACT FROM AUTHOR]

Aim: To clarify the role of Eomesodermin (EOMES) to serve as a disease‐relevant biomarker and the intracellular molecules underlying the immunophenotype shifting of CD4+T subsets in amyotrophic lateral sclerosis (ALS). Methods: The derivation and validation cohorts included a total of 148 ALS patients and 101 healthy controls (HCs). Clinical data and peripheral blood were collected. T‐cell subsets and the EOMES expression were quantified using multicolor flow cytometry. Serum neurofilament light chain (NFL) was measured. In 1‐year longitudinal follow‐ups, the ALSFRS‐R scores and primary endpoint events were further recorded in the ALS patients of the validation cohort. Results: In the derivation cohort, the CD4+EOMES+T‐cell subsets were significantly increased (p < 0.001). EOMES+ subset was positively correlated with increased serum NFL levels in patients with onset longer than 12 months. In the validation cohort, the elevated CD4+EOMES+T‐cell proportions and their association with NFL levels were also identified. The longitudinal study revealed that ALS patients with higher EOMES expression were associated with higher progression rates (p =.010) and worse prognosis (p =.003). Conclusions: We demonstrated that increased CD4+EOMES+T‐cell subsets in ALS were associated with disease progression and poor prognosis. Identifying these associations may contribute to a better understanding of the immunopathological mechanism of ALS. [ABSTRACT FROM AUTHOR]

Summary: Maize is one of the most important crops for food, cattle feed and energy production. However, maize is frequently attacked by various pathogens and pests, which pose a significant threat to maize yield and quality. Identification of quantitative trait loci and genes for resistance to pests will provide the basis for resistance breeding in maize. Here, a β‐glucosidase ZmBGLU17 was identified as a resistance gene against Pythium aphanidermatum, one of the causal agents of corn stalk rot, by genome‐wide association analysis. Genetic analysis showed that both structural variations at the promoter and a single nucleotide polymorphism at the fifth intron distinguish the two ZmBGLU17 alleles. The causative polymorphism near the GT‐AG splice site activates cryptic alternative splicing and intron retention of ZmBGLU17 mRNA, leading to the downregulation of functional ZmBGLU17 transcripts. ZmBGLU17 localizes in both the extracellular matrix and vacuole and contribute to the accumulation of two defence metabolites lignin and DIMBOA. Silencing of ZmBGLU17 reduces maize resistance against P. aphanidermatum, while overexpression significantly enhances resistance of maize against both the oomycete pathogen P. aphanidermatum and the Asian corn borer Ostrinia furnacalis. Notably, ZmBGLU17 overexpression lines exhibited normal growth and yield phenotype in the field. Taken together, our findings reveal that the apoplastic and vacuolar localized ZmBGLU17 confers resistance to both pathogens and insect pests in maize without a yield penalty, by fine‐tuning the accumulation of lignin and DIMBOA. [ABSTRACT FROM AUTHOR]

The utilization of hot carriers as a means to surpass the Shockley‐Queasier limit represents a promising strategy for advancing highly efficient photovoltaic devices. Quantum dots, owing to their discrete energy states and limited multi‐phonon cooling process, are regarded as one of the most promising materials. However, in practical implementations, the presence of numerous defects and discontinuities in colloidal quantum dot (CQD) films significantly curtails the transport distance of hot carriers. In this study, the harnessing of excess energies from hot‐carriers is successfully demonstrated and a world‐record carrier diffusion length of 15 µm is observed for the first time in colloidal systems, surpassing existing hot‐carrier materials by more than tenfold. The observed phenomenon is attributed to the specifically designed honeycomb‐like topological structures in a HgTe CQD superlattice, with its long‐range periodicity confirmed by High‐Resolution Transmission Electron Microscopy(HR‐TEM), Selected Area Electron Diffraction(SAED) patterns, and low‐angle X‐ray diffraction (XRD). In such a superlattice, nonlocal hot carrier transport is supported by three unique physical properties: the wavelength‐independent responsivity, linear output characteristics and microsecond fast photoresponse. These findings underscore the potential of HgTe CQD superlattices as a feasible approach for efficient hot carrier collection, thereby paving the way for practical applications in highly sensitive photodetection and solar energy harvesting. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The ORAL Surveillance trial found a dose‐dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance.Patients with rheumatoid arthritis (RA) aged 50 years or older with at least one additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (patients with first events/100 patient‐years) by 6‐month intervals were estimated for adjudicated VTE, deep vein thrombosis, and PE. Cox regression models identified risk factors. Clinical Disease Activity Index leading up to the event was explored in patients with VTE.Cumulative probabilities for VTE and PE were higher with tofacitinib 10 mg BID, but not 5 mg BID, versus TNFi. Incidence rates were consistent across 6‐month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index greater than or equal to 35 kg/m2, older age, and history of chronic lung disease. At the time of the event, most patients with VTE had active disease as defined by Clinical Disease Activity Index.Incidences of VTE and PE were higher with tofacitinib (10 > 5 mg BID) versus TNFi and were generally consistent over time. Across treatments, VTE risk factors were aligned with previous studies in the general RA population. These data highlight the importance of assessing VTE risk factors, including age, body mass index, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA. [ABSTRACT FROM AUTHOR]

Background: Several studies have been conducted on using platelet‐rich plasma (PRP) to treat cosmetic issues. Nonetheless, no bibliometric analyses of publications in this field exist. Bibliometrics is an effective tool for methodically assessing the current state of research on a particular topic. This study examines the literature published in this field since 2000 and depicts the resulting network. Methods: The Web of Science Core Collection was searched for any publications mentioning the use of PRP in cosmetic or aesthetic therapy published between 2001 and 2022. The author, region, institution, journal, cited journal, and keywords were extracted, and the bibliometric analysis was carried out using CiteSpace and R studio. Results: There were a total of 306 items retrieved. The first publication in this field appeared in 2001, and the number of articles published increased over the next 21 years. Saedi Nazanin is the author with the most publications. The most prolific nations and institutions were the United States and the Fourth Military Medical University, respectively. Similarly, most articles and citations were found in the Journal of Cosmetic Dermatology and Plastic and Reconstructive Surgery. After performing a cluster analysis on the keywords of published publications, we discovered that most of the published literature focused on using PRP in rejuvenation, mechanism, and combination with MSCs. These topics are still at the frontier of future research. Conclusion: Since the first study in this field was published in 2001, PRP used in cosmetic clinics has been studied. Although early effects have been observed, numerous challenges remain, including a lack of higher‐quality clinical studies and explanations of PRP's mechanism. The bibliometric analysis conducted for the purpose of this article provides a summary of academic hotspots and research frontiers, as well as insights and pointers for future productive research. [ABSTRACT FROM AUTHOR]

Electrocatalysis plays a pivotal role in renewable energy conversion and associated chemical production, enabling a variety of emerging sustainability technologies with societal impacts. Achieving marked improvement in electrocatalytic performance relies on a deep understanding of catalyst microstructures and catalytic mechanisms, with a particular emphasis on the detailed, spatiotemporally resolved characterizations of the underlying fundamental electrocatalytic processes. This fundamental need drives the development of operando imaging techniques, which improve the ability to detect dynamic structural changes in electrocatalysts and establish clear structure‐performance relationships for morphologically complex, hierarchically structured catalytic materials. This review aims to highlight significant advancements in the application of operando imaging techniques to develop a deeper understanding of important heterogeneous electrocatalytic reactions critical for emerging sustainability technologies. We summarize the up‐to‐date key mechanistic insights regarding these reactions achieved through a range of operando imaging techniques, including electron microscopies, X‐ray imaging techniques, scanning probe microscopies, and optical microscopies. We conclude by pointing out emerging directions and future prospects within the field of operando imaging in electrocatalysis. [ABSTRACT FROM AUTHOR]

Background: End‐stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). Aims: We aimed to analyze the expression differences of serum thrombomodulin (TM), platelet‐activating factor (PAF), and P‐selectin (CD62P) in patients with autologous arteriovenous fistula (AVF) and the correlation with vascular access function. Methods: The case data were retrospectively analyzed. Moreover, 160 patients with AVF maintenance hemodialysis were selected as the AVF group, and 150 healthy participants were selected as the healthy control group. According to the function of vascular access, patients in the AVF group were divided into Group A (n = 50, after the first establishment of AVF), Group B (n = 64, normal vascular access function after hemodialysis treatment), and Group C (n = 46, vascular access failure). Pearson analysis was conducted to explore the correlation between serum TM, PAF, CD62P content, and vascular pathological examination indicators, to evaluate the value of TM, PAF, and CD62P levels in predicting vascular access failure in patients with AVF. Results and Discussion: The serum levels of TM, PAF, and CD62P were positively correlated with the expressions of CD68 and MCP‐1, respectively (p <.001). Serum TM was positively correlated with the levels of PAF and CD62P (p <.001), and PAF was positively correlated with the levels of CD62P (p <.001), respectively. Serum levels of TM, PAF and CD62P were risk factors for vascular access failure in AVF patients (p <.05). The area under the curve of serum TM, PAF and CD62P levels in predicting vascular access failure in AVF patients was 0.879. Conclusion: The serum levels of TM, PAF, and CD62P in AVF patients were correlated with the vascular access function of AVF patients, which was very important for maintaining the stability of vascular access function, and had certain value in predicting vascular access failure/disorder in AVF patients, and could be popularized and applied. [ABSTRACT FROM AUTHOR]

Leonurine (LEO), an alkaloid isolated from Leonurus spp., has anti‐oxidant, anti‐inflammatory and anti‐apoptotic effects and can prevent damage caused by reactive oxygen species (ROS). These properties suggest that it can improve the maturation rate of oocytes and developmental ability of embryos, which are key parameters in animal breeding. In this study, the effects of LEO on in vitro maturation and early embryonic development in sheep oocytes were evaluated. Among various doses examined (0, 10, 20 and 40 μM), a dose of 20 μM was optimal with respect to the oocyte maturation rate. Compared with estimates in the control group, GSH levels and mitochondrial membrane potential of sheep oocytes treated with 20 μM LEO were significantly higher, and 40 μM LEO would affect oocyte maturation. Additionally, ROS levels were significantly lower, expression levels of the antioxidant genes CAT and SOD1 were significantly higher, and there was no significant difference in GPX3 expression. The Bax/Bcl‐2 ratio and Caspase‐3 expression were significantly reduced in the 20 μM LEO group. During early embryonic development in vitro, the cleavage rate and blastocyst rate were significantly higher in the 20 μM LEO treatment group compared to other groups. GSH levels and mitochondrial membrane potential were significantly higher, while ROS levels were significantly lower, and expression levels of the antioxidant genes CAT, GPX3 and SOD1 were significantly higher in eight‐cell embryos treated with 20 μM LEO than in the control group. The Bax/Bcl‐2 ratio and Caspase‐3 levels were significantly decreased. In summary, LEO can reduce the effect of oxidative stress, improve the oocyte maturation rate and enhance embryonic development. [ABSTRACT FROM AUTHOR]

Development of low‐cost electrocatalysts for water splitting is crucial to economical hydrogen production. Here, a highly efficient electrocatalyst composed of MoNi4‐embedded amorphous MoO2 nanosheets grown on less‐tortuosity hierarchically porous carbonized wood (MoNi4/MoO2@CW) is reported. The generation of abundant MoNi4/MoO2 heterointerfaces and defects‐rich MoO2 significantly promote the adsorption and activation of reactant molecules on the MoNi4/MoO2@CW. The obtained MoNi4/MoO2@CW catalyst exhibits ultralow overpotentials of 22 and 205 mV for hydrogen evolution reaction and oxygen evolution reaction at a current density of 10 mA cm−2, respectively. The catalyst can be used for dual‐function electrodes and assembling two‐electrode electrolyzer illustrates 10 mA cm−2 at 1.47 V and superior durability over 24 h for overall water electrolysis. Moreover, it also possesses a high mass activity of 142 Ag−1 MoNi4 at 200 mV, surpassing the Pt/C catalyst (132 Ag−1). The outstanding performance of the MoNi4/MoO2@CW is attributed to the decrease in energy barrier for water dissociation, optimal adsorption/desorption of H/O‐intermediates, and fast mass transport through the porous structure, as confirmed by experimental results and density functional theory‐based calculations. The MoNi4/MoO2@CW electrocatalyst has excellent potential for practical water splitting. [ABSTRACT FROM AUTHOR]

π‐π interactions, serving as a pivotal driving force, hold enduring significance in the realm of drug delivery system development, primarily due to the prevalence of aromatic moieties in a substantial number of clinically relevant pharmaceutical compounds. Herein, we constructed a novel carbon nitride compound called PTCNx, featuring a large π‐conjugated skeleton, and employed it as a carrier for delivering aromatic clinical drugs for the first time. We conducted sequence characterization of their chemical structure, optical properties, and morphology, along with extensive research to analyze their significant enhancement in drug loading capacity. Of particular note was the exceptional loading efficiency of Doxorubicin (DOX) under alkaline conditions, achieving an unexpected 99 % efficacy, significantly surpassing the capabilities of traditional carbon nitrides with limited π‐conjugated systems. Cell tests illustrated that PTCN550 carrier exhibited favorable biocompatibility and low toxicity for normal and tumor cells, showing its potential as a drug carrier. However, PTCN550‐DOX complex effectively inhibited both A549 and CNE‐2Z tumor cells. And it demonstrated more effective anti‐tumor activity for CNE‐2Z than for A549 cells. This study marks a significant milestone, representing the inaugural endeavor to elucidate the improvement in loading capacity through the strategic extension of the π‐conjugated system design paradigm. [ABSTRACT FROM AUTHOR]

A convenient and efficient reagent system of arylhydrazine salt‐selenium was developed to directly selenizing uracil preparation of 5‐selenium uracil. In the presence of this reagent, a variety of uracil/pyrimidine converts to their corresponding 5‐arylselanyluracils/5‐selenopyrimidine with good yield and high regioselectivity. Elemental selenium of commercially accessible, stable, affordable, and easy to use was used as the selenization reagent. This reaction is attractive and practical since there are no catalysts or ligands needed, and a wide range of functional groups can be tolerated. [ABSTRACT FROM AUTHOR]

Purpose of Review: Parkinson's disease (PD) is a common neurodegenerative disease, which can cause progressive deterioration of motor function causing muscle stiffness, tremor, and bradykinesia. In this review, we hope to describe approaches that can improve the life of PD patients through modifications of energy metabolism. Recent Findings: The main pathological features of PD are the progressive loss of nigrostriatal dopaminergic neurons and the production of Lewy bodies. Abnormal aggregation of α‐synuclein (α‐Syn) leading to the formation of Lewy bodies is closely associated with neuronal dysfunction and degeneration. The main causes of PD are said to be mitochondrial damage, oxidative stress, inflammation, and abnormal protein aggregation. Presence of abnormal energy metabolism is another cause of PD. Many studies have found significant differences between neurodegenerative diseases and metabolic decompensation, which has become a biological hallmark of neurodegenerative diseases. Summary: In this review, we highlight the relationship between abnormal energy metabolism (Glucose metabolism, lipid metabolism, and amino acid metabolism) and PD. Improvement of key molecules in glucose metabolism, fat metabolism, and amino acid metabolism (e.g., glucose‐6‐phosphate dehydrogenase, triglycerides, and levodopa) might be potentially beneficial in PD. Some of these metabolic indicators may serve well during the diagnosis of PD. In addition, modulation of these metabolic pathways may be a potential target for the treatment and prevention of PD. [ABSTRACT FROM AUTHOR]

Erbium (Er)‐doped III‐V semiconductors are promising for optoelectronic devices due to the unique intra‐4f electronic transitions of Er3+; however, the Er‐related luminescence at room temperature has always been challenging to obtain. In this work, High crystalline quality ErAs:GaAs films are grown with self‐assembled ErAs nanoparticles embedded within the GaAs matrix by molecular beam epitaxy. Rich photoluminescence spectra in a broad wavelength ranging from near‐ultraviolet to near‐infrared are observed at room temperature and confirmed to be Er‐related. A carrier‐mediated energy transfer up‐conversion mechanism is proposed, and the pump power‐dependent photoluminescence results reveal that the excited‐state absorption is governed by a single photonic process. The efficient interaction and energy transfer between the semiconductor matrix and Er3+ ions offered by this unique nanocomposite material provide a promising route to achieve novel optoelectronic devices with the potential to cover a broad wavelength range. [ABSTRACT FROM AUTHOR]

Abstract: Mitochondrial thioredoxin (mtTrx) can be oxidized in response to inducers of oxidative stress; yet the functional consequences of the oxidation have not been determined. This study evaluated the redox status of mtTrx and its association to oxidant-induced apoptosis. Results showed that mtTrx was oxidized after exposure to peroxides and diamide. Overexpression of mtTrx protected against diamide-induced oxidation and cytotoxicity. Oxidation of mtTrx was also achieved by knocking down its reductase; and lead to increased susceptibility to cell death. The data indicate that the redox status of mtTrx is a regulatory mechanism underlying the vulnerability of mitochondria to oxidative injury. [Copyright &y& Elsevier]

Background: Ameloblastic fibroma (AF) and related lesions constitute a group of lesions, which range in biologic behavior from true neoplasms to hamartomas. The aim of this study was to elucidate the nature and interrelationship of this group of lesions. Methods: Clinical and pathological studies were undertaken retrospectively on 13 cases of AF and seven cases of ameloblastic fibro-odontoma (AFO). Thirty-three complex odontomas and 33 compound odontomas were also included for comparative purpose. Relevant follow-up data were recorded and the literature was reviewed. Results: The majority of patients with AF (nine cases, 69.2%) were over the age of 22 years with frequent involvement (76.9%) of the posterior mandible. Tumors recurred in four of 11 patients with follow-up information and two recurrent tumors showed malignant transformation. There was no case in this series that could be designated as the so-called ameloblastic fibrodentinoma, apart from one recurrent AF in which further maturation to form only tubular dentin materials was identified. AFO tended to occur at a younger age group with an average of 9.6 years. Recurrence was noted in two of five patients with follow-up data and both recurrent lesions showed limited growth potential and further maturation into a complex odontoma. Significant differences were noted in the age and site distribution between the complex and the compound odontomas. Conclusion: Whilst the majority, if not all, of AFs are true neoplasms with a potential to recur and/or of malignant transformation, some, especially those occurred during childhood, could represent the primitive stage of a developing odontoma. Our data also suggests that some AFOs are hamartomatous in nature, representing a stage preceding the complex odontoma. [ABSTRACT FROM AUTHOR]

While the incorporation of geographical and environmental modeling with GIS requires software support for storage and retrieval of spatial information that changes over time, it continues to be an unresolved issue with modern GIS software. Two complementary approaches have been used to manage the spatial and temporal heterogeneity within datasets that use a field-based representation of the world. Some researchers have proposed new data models that partition space into discrete elements on an as-needed basis following each temporal event, while others have focused on eliminating duplication of repeated data elements present in spatio-temporal information. It is proposed in this paper that both approaches have merit and can be combined to create a Hybrid Spatio-Temporal Data Model and Structure (HST-DMS) that efficiently supports spatio-temporal data storage and querying. Specifically, Peuquet and Duan's (1995) Event-based Spatio-Temporal Data Model (ESTDM) and the Overlapping R-tree (Guttman 1984, Tzourmanis et al. 2000) are utilized to create a prototype used to store information about urban expansion for the town of Carbondale, Illinois. [ABSTRACT FROM AUTHOR]

An expression cassette containing mouse U6 polymerase III promoter directing expression of short hairpin RNA (shRNA) targeting murine microsomal glucose-6-phosphatase (G6P) transcript was generated. This construct was packaged into an adenoviral (AdV) backbone and viral stocks generated. Mice injected intravenously with AdV-G6PshRNA exhibited a significant reduction in postprandial glucose levels and had significantly elevated steady-state hepatic glycogen stores. Target gene silencing was confirmed by measurements demonstrating a significant reduction in both hepatic G6P transcript level and phosphohydrolase activity. These findings provide evidence that AdV delivery of expressed shRNA can be a productive tool to explore gene function in vivo. [Copyright &y& Elsevier]

Defines the changes in the redox state of glutathione and thioredoxin that occur as cells progress from a proliferating state to a more differentiated state and to apoptosis. Expression of the redox state; Redox reactions involving thioredoxin; Potential for cellular regulation via thioredoxin and glutathione redox.

Latent transforming growth factor-β (TGF-β) binding protein (LTBP)-1, which is easily secreted, has been shown to enhance the secretion of TGF-β. Here we show that another member of the LTBP family, LTBP-3, is not secreted by several cell types, but secretion occurs after coexpression with TGF-β. The secretion of LTBP-3 requires complexing of LTBP-3 with Cys33 of the TGF-β propeptide. [Copyright &y& Elsevier]

Mechanical metamaterials are of tremendous research interest due to their unconventional properties that arise from unit microstructure. Shape‐reconfiguration is an effective method to realize programmability on various properties for different tasks of a structure or system, while existing researches focus on multiple degree‐of‐freedom (DOF) systems or limited configurations that morph along a single kinematic path. Here, starting from a one‐DOF Wohlhart polyhedron module, its interesting topological transformation is explored along multiple motion paths through kinematic bifurcations, accompanied by tunable mechanical properties, including Poisson's ratio, chirality, and stiffness. Furthermore, these modules are tessellated into 3D metamaterials to harness their reconfigurability to independently program the Poisson's ratios in orthogonal planes within a wide range of negative Poisson's ratio, positive Poisson's ratio, and even zero Poisson's ratio. This work opens up avenues for the design of programmable metamaterials based on the perspective of kinematic bifurcation generating from single DOF systems, which can readily be applied in shape‐morphing systems in various fields, such as flexible metamaterials, morphing architectures, and deployable structures. [ABSTRACT FROM AUTHOR]

Soft electrothermal actuators are widely used in soft robots, smart switches, medical devices, artificial muscles, and human--machine interactions. Generally, they operate at room temperature but also meet the safety standards for maximum safe voltage for a human body. Therefore, an actuator with a lower voltage and lower temperature is the first choice, as long as the performance is not affected. In this study, a bilayer film based on polythene (PE)/graphite is used to realize an electrothermal drive. The method is simple, inexpensive, and convenient for mass production. At a low driving voltage of between 1.5 and 2 V, and at a temperature of 40-52 °C, a maximum bending angle of 139.22°-470°. Through the demonstration of a micromechanical gripper and transportation illustrated by drug crawling, it is proven that the PE/graphite composite membrane can be widely applied in the field of soft actuators. [ABSTRACT FROM AUTHOR]

This paper presents a voxel-based biomechanical model for muscle deformation using finite element method (FEM) and volume graphics. Hierarchical voxel meshes are reconstructed from filtered segmented muscle images followed by FEM simulation and volume rendering. Physiological muscle force is considered and linear elastic muscle models for both static and dynamic cases are simulated by FEM. Voxel-based wireframe, polygon surface rendering, and volume rendering techniques are applied to show real-time muscle deformation processes as well as realistic animations. [ABSTRACT FROM AUTHOR]

Osteoporosis is a systemic bone metabolism disorder, which increases the risk of fractures, and in severe cases it may cause disability or even death. An important factor contributing to osteoporosis is the imbalance between bone formation and resorption. Naringin was reported to promote osteoblast differentiation, thus enhancing bone formation and alleviating osteoporosis development. However, the signalling pathways related to the regulatory mechanism of naringin in osteoporosis development are not clear. Proliferation of bone mesenchymal stem cells (BMSCs) treated with naringin in vitro was detected by CCK‐8. An osteogenesis differentiation medium supplemented with naringin was applied to explore the effects of naringin on BMSC osteogenic differentiation, as detected by Alizarin red staining. Ovariectomy (OVX)‐induced postmenopausal osteoporosis (PMOP) rats were orally administered with naringin. Dual‐energy X‐ray absorptiometry (DEXA) and micro‐CT were applied to measure bone mineral density (BMD), bone volume/total volume (BV/TV), trabecula thickness (Tb.Th), trabecula number (Tb.N), trabecular separation (Tb.Sp) and bone surface/bone volume (BS/BV). H&E staining was performed to show pathological changes of the femur in PMOP rats after naringin treatment. Bone metabolism indicators were assessed by ELISA. We found that naringin suppressed the activation of the JAK2/STAT3 pathway. Naringin promoted BMSC proliferation and osteogenic differentiation. Furthermore, naringin alleviates bone loss and improves abnormal bone metabolism of PMOP rats. Collectively, naringin promotes BMSC osteogenic differentiation to ameliorate osteoporosis development by targeting JAK2/STAT3 signalling. [ABSTRACT FROM AUTHOR]

GLO:F2H7/01nov21:ctm2586-fig-0001.jpg PHOTO (COLOR): 1 Pharmacogenomics (PGx) testing unit and characteristics of the participants, tested genes, drugs, diseases, and variants. Analytics of the clinical implementation of pharmacogenomics testing in 12 758 individuals Pharmacogenomics (PGx) testing is still not widely accepted in routine medical practice, with one of the major obstacles being the lack of evidence to support its clinical benefit.1,2 In the Chinese population, large-scale comprehensive analytics of clinical PGx testing are still lacking.3,4 Thus, we analysed clinical PGx testing for personalised drug treatment in 12,758 Chinese patients at Xiangya Hospital of Central South University, which is one of the first institutions to conduct clinical PGx testing in China. All tested drugs and genes were sorted by the recommendation percentage, which was equal to that of the samples that received PGx recommendations (including risk warnings) divided by the total samples tested for each gene or drug. [Extracted from the article]

As a traditional Chinese medicine, Eupatorium lindleyanum DC. has an effect on resolving phlegm, relieving cough, and relieving asthma. In this study, an ultra high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry method was established for qualitative analysis of Eupatorium lindleyanum. Besides, we developed an ultra high performance liquid chromatography with triple quadrupole tandem mass spectrometry method in positive and negative multiple reaction monitor modes for the quantitative analysis of 27 chemical constituents from 19 different batches of Eupatorium lindleyanum. The methodology validated linearity, intraday and interday precision, stability, repeatability, and recovery. The results showed that there were some differences in different batches of Eupatorium lindleyanum, which might be attributed to the influence of different growth environments and climatic conditions on the accumulation of compounds. The variable importance of projection value of orthogonal partial least square discriminant analysis and anti‐inflammatory activity test showed that eupalinolide A, B, C, and K have high content and strong activity, which could provide a reference for the follow‐up study of the quality markers of Eupatorium lindleyanum. Collectively, we developed a rapid and efficient method for the qualitative analysis and simultaneous quantification of Eupatorium lindleyanum, which was beneficial for the comprehensive utilization and development of resources. [ABSTRACT FROM AUTHOR]

As the core process of natural gas purification plant, natural gas sweetening directly affects the production efficiency and product quality of the purification plant. However, process modeling based on sulfur content prediction presents challenges in adaptability and accuracy. To tackle this, a machine learning‐based modeling approach is proposed that integrates an adaptive immune genetic algorithm with random forest (RF) to intelligently select process features as input variables for RF modeling. The industrial result indicates that the proposed method is able to remove interfering variables and adaptively achieve optimal model precision for different scenarios. It offers a novel research instrument for product quality monitoring in natural gas sweetening plants. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Different types of diabetes show distinct genetic characteristics, but the specific genetic susceptibility factors remain unclear. Our study aimed to explore the associations between the ribosomal protein S26 (RPS26) gene rs1131017 polymorphisms and susceptibility to type 1 diabetes mellitus, latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus in the Chinese Han population, and their correlations with clinical features. Materials and Methods: Genotyping of the rs1131017 variant was carried out for 1,006 type 1 diabetes mellitus patients, 210 LADA patients, 642 type 2 diabetes mellitus patients and 2,099 control individuals. Results: We found that the rs1131017 C allele was a risk locus for both type 1 diabetes mellitus and LADA (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.33–1.69, P < 0.001; OR 1.31, 95% CI 1.04–1.64, P = 0.021, respectively). Nevertheless, this association was not found for type 2 diabetes mellitus. Carrying the C allele genotype was associated with a lower postprandial C‐peptide for type 1 diabetes mellitus (OR 1.41, 95% CI 1.11–1.80, P = 0.006) and lower fasting C‐peptide for LADA (OR 1.55, 95% CI 1.01–2.38, P = 0.047). Interestingly, a lower GC frequency was noted for LADA than for type 1 diabetes mellitus, regardless of classification based on age at diagnosis, C‐peptide or glutamic acid decarboxylase antibody positivity. Conclusions: The RPS26 polymorphism was associated with susceptibility and clinical characteristics of type 1 diabetes mellitus and LADA in the Chinese population, but was not related to type 2 diabetes mellitus. Thus, it might serve as a novel biomarker for particular types of diabetes. In this manuscript, we explored whether RPS26 gene polymorphisms conferred susceptibility to type 1 diabetes mellitus, latent autoimmune diabetes in adults and type 2 diabetes mellitus in a considerably large collection of Chinese participants. The effects of this gene on clinical features of patients, including age at diagnosis, β‐cell function, and islet autoantibodies were also comprehensively investigated. We have found that the SNP, rs1131017, of the RPS26 gene is a genetic susceptibility locus for type 1 diabetes mellitus and latent autoimmune diabetes in adults in the Chinese Han population, but it has no impact on susceptibility to type 2 diabetes mellitus. Our research provides evidence for the important role of RPS26 in the genetic susceptibility of type 1 diabetes mellitus, offering a new biomarker for risk assessment and precise diagnosis of diabetes. [ABSTRACT FROM AUTHOR]

Deubiquitylating enzymes (DUBs) maintain relative homeostasis of the cellular ubiquitome by removing the post‐translational modification ubiquitin moiety from substrates. Numerous DUBs have been demonstrated specificity for cleaving a certain type of ubiquitin linkage or positions within ubiquitin chains. Moreover, several DUBs perform functions through specific protein–protein interactions in a catalytically independent manner, which further expands the versatility and complexity of DUBs' functions. Dysregulation of DUBs disrupts the dynamic equilibrium of ubiquitome and causes various diseases, especially cancer and immune disorders. This review summarizes the Janus‐faced roles of DUBs in cancer including proteasomal degradation, DNA repair, apoptosis, and tumor metastasis, as well as in immunity involving innate immune receptor signaling and inflammatory and autoimmune disorders. The prospects and challenges for the clinical development of DUB inhibitors are further discussed. The review provides a comprehensive understanding of the multi‐faced roles of DUBs in cancer and immunity. [ABSTRACT FROM AUTHOR]

Background and Aim: The spatial distribution and interactions of cells in the tumor immune microenvironment (TIME) might be related to the different responses of triple‐negative breast cancer (TNBC) to immunomodulators. The potential of multiplex IHC (m‐IHC) in evaluating the TIME has been reported, but the efficacy is insufficient. We aimed to research whether m‐IHC results could be used to reflect the TIME, and thus to predict prognosis and complement the TNBC subtyping system. Methods: The clinical, imaging, and prognosis data for 86 TNBC patients were retrospectively reviewed. CD3, CD4, CD8, Foxp3, PD‐L1, and Pan‐CK markers were stained by m‐IHC. Particular cell spatial distributions and interactions in the TIME were evaluated with the HALO multispectral analysis platform. Then, we calculated the prognostic value of components of the TIME and their correlations with TNBC transcriptomic subtypes and MRI radiomic features reflecting TNBC subtypes. Results: The components of the TIME score were established by m‐IHC and demonstrated positive prognostic value for TNBC (p = 0.0047, 0.039, <0.0001 for DMFS, RFS, and OS). The score was calculated from several indicators, including Treg% in the tumor core (TC) or stromal area (SA), PD‐L1+ cell% in the SA, CD3 + cell% in the TC, and PD‐L1+/CD8+ cells in the invasive margin and SA. According to the TNBC subtyping system, a few TIME indicators were significantly different in different subtypes and significantly correlated with MRI radiomic features reflecting TNBC subtypes. Conclusion: We demonstrated that the m‐IHC‐based quantitative score and indicators related to the spatial distribution and interactions of cells in the TIME can aid in the accurate diagnosis of TNBC in terms of prognosis and classification. [ABSTRACT FROM AUTHOR]

Morphine tolerance (MT) is currently a challenging issue related to intractable pain treatment. Studies have shown that reactive oxygen species (ROSs) derived from NADPH oxidase (NOX) and produced in response to endoplasmic reticulum (ER) stress participate in MT development. However, which NOX subtype initiates ER stress during MT development is unclear. NOX4 is mainly expressed on intracellular membranes, such as the ER and mitochondrial membranes, and its sole function is to produce ROS. Whether NOX4 is activated during MT development and the mechanisms underlying the association between NOX4 and ER stress during this process still need to be confirmed. In our study, we used the classic morphine‐tolerant rat model and evaluated the analgesic effect of intrathecally injected morphine through a hot water tail‐flick assay. Our research demonstrated for the first time that chronic morphine administration upregulates NOX4 expression in the spinal cord by activating three ER stress sensors, protein kinase RNA‐like ER kinase (PERK), inositol‐requiring enzyme 1 (IRE1) and activating transcription factor 6 (ATF6), subsequently leading to the activation of microtubule‐associated protein 1 light chain 3 b (LC3B) and P62 (a well‐known autophagy marker) in GABAergic neurons. Our results may suggest that regulating NOX4 and the key mechanism underlying ER stress or autophagy may be a promising strategy to treat and prevent MT development. [ABSTRACT FROM AUTHOR]

Introduction: Many asthmatic patients are exposed to cigarette smoke actively or passively, which contributes to asthma exacerbation and poor control. This study is to explore the effects of cigarette smoke on pathological changes in murine surrogate of asthma. Methods: C57BL/6 mice were sensitised and challenged with ovalbumin (OVA) to establish a surrogate of asthma and then administered with cigarette smoke extract (CSE). Airways hyperresponsiveness (AHR) was measured using the Flexivent system. Histological staining (haematoxylin‐eosin [HE], periodic acid Schiff [PAS], Congo red and Masson's trichrome) was employed to measure pathological changes in sections of lung tissue of experimental mice. Enzyme‐linked immunosorbent assay (ELISA) was used to measure the concentrations of total and OVA‐specific IgE, cytokines and chemokines (eotaxin‐1, IL‐13, IL‐1β, TNF‐α, IL‐17A, IL‐33) in the lung tissue homogenates. Immunoreactivity for vWF and α‐SMA in lung tissue sections was detected by immunohistochemistry. Results: Exposure of the animals to CSE significantly reduced OVA‐induced AHR, the number of eosinophils in bronchoalveolar lavage fluid (BALF) and eosinophils infiltrating into the lung tissue, as well as concentrations of some cytokines in lung homogenate. In contrast, it significantly enhanced the number of macrophages and M2 in BALF, as well as collagen deposition, smooth muscle thickness and alveolar destruction in lung tissue. Conclusion: CSE inhibits OVA‐induced AHR, changes inflammation 'phenotypes', while accelerates some aspects of airways remodelling, which might contribute to worse symptoms and be refractory to anti‐inflammation therapies for asthmatics. [ABSTRACT FROM AUTHOR]

Background: Diterpene ginkgolides meglumine injection (DGMI) is a platelet‐activating factor receptor (PAFR) antagonist that can be used to treat acute ischemic stroke (AIS). This study evaluated the efficacy and safety of an intensive antiplatelet strategy based on PAFR antagonists and explored the underlying mechanisms of PAFR antagonists in AIS treatment. Methods: This is a retrospective study applying propensity score methods to match AIS patients treated with DGMI to nontreated patients. The primary outcome was functional independence (modified Rankin Scale [mRS] 0–2) at 90 days. The safety outcome was bleeding risk. We used McNemar test to compare the efficacy outcome. Subsequently, the network pharmacology analysis was performed. Results: 161 AIS patients treated with DGMI in the study were matched with 161 untreated patients. Compared with untreated patients, DGMI‐treated patients had a significantly higher rate of mRS ranking 0–2 at 90 days (82.0% vs. 75.8%, p < 0.001), without increased risk of bleeding. The gene enrichment analysis showed that the overlap genes of DGMI targeted and AIS‐related enriched in thrombosis and inflammatory‐related signaling pathways. Conclusions: An intensive antiplatelet strategy of DGMI plus traditional antiplatelet agents is effective in treating AIS and may work by mediating post‐stroke inflammation and thrombosis. [ABSTRACT FROM AUTHOR]

Background: The primary aim of the present study was to explore risk factors for portal vein system thrombosis following splenectomy. Methods: A systematic search of PubMed, Embase and Cochrane libraries was conducted to identify original studies that fulfilled the inclusion criteria. Raw data on potential risk factors for portal vein system thrombosis after splenectomy were extracted for meta‐analysis. Subsequently, a sensitivity analysis was conducted to verify the stability of the results. Results: Eighteen studies with 626 thrombosis events from 1807 splenectomy met the inclusion criteria. Larger spleen volume (SMD 0.44, P = 0.000), broader splenic vein diameter (WMD 2.30, P = 0.000), broader portal vein diameter (WMD 2.08, P = 0.000), a lower velocity of portal blood flow (WMD −0.91, P = 0.001), decreased platelet count (WMD −5.14, P = 0.007), decreased white blood cell (WMD −0.40, P = 0.027), decreased haemoglobin (WMD −9.14, P = 0.002), ascites (OR 1.81, P = 0.003) and bleeding history before surgery (OR 1.88, P = 0.002) were identified to be factors that exacerbated the risk of portal vein system thrombosis after splenectomy. Sex, age, preoperative prothrombin time, postoperative platelet count, postoperative D‐dimer, operation time and intraoperative blood loss, did not increase the risk of thrombosis. Conclusion: Larger spleen volume, broader splenic vein diameter, broader portal vein diameter, a lower velocity of portal blood flow, ascites, bleeding history before surgery, decreased platelet count, white blood cell and haemoglobin may increase the risk of portal vein system thrombosis. [ABSTRACT FROM AUTHOR]

Sepsis is a life‐threatening disease characterized by multiple organ dysfunction. B cells play a pivotal role in sepsis. Here, we first observed the significantly reduced Flot2 gene expression in B cells from patients with bacterial sepsis and endotoxin‐induced septic mice. However, the effects of Flot2 on sepsis and B‐cell immunity remain unknown. Thus, we sorted B cells from Flot2 knockout (Flot2−/−) mice, RNA‐seq revealed significantly upregulated effector B cell (Beff) cytokines such as Il6, Il1b and Cxcl10 after Flot2 deficiency, while it showed no effect on the expression of regulatory B cell (Breg) cytokines such as Il10, Tgfb. Consistently, elevated Beff cytokine IL‐6 and unchanged Breg cytokine IL‐10 were shown in B cells from Flot2−/− mice. Similar results were subsequently observed in B cell‐specific Flot2 knockout chimeric mice. Notably, Flot2 deficiency aggravated sepsis with increased lung injury and shortened survival time in vivo by facilitating Beffs but not Bregs. Taken together, our data identify Flot2 as a novel controller of B cells, Flot2 deficiency amplifies inflammation by affecting Beffs to participate in the pathogenesis and progression of sepsis. [ABSTRACT FROM AUTHOR]

Spin crossover (SCO) materials with new architectures will expand and enrich the research in the SCO field. Here, we report two metal–organic frameworks (MOFs) containing tetradentate organic ligands and hexatopic linkers [Ag8X8(CN)6]6− (X=Br and I), which represents the first SCO MOF with clusters as building blocks. The silver halide cluster can be further removed after reacting with lithium tetracyanoquinodimethan (LiTCNQ). Such post‐synthetic modification (PSM) is realized via single‐crystal to single‐crystal (SCSC) transformation from urk to nbo topology. Accordingly, the spin state and fluorescence properties are greatly modified by cluster deconstruction. Therefore, these achievements will provide new ideas for the design of new SCO systems and the development of PSM methods. [ABSTRACT FROM AUTHOR]