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Ethnopharmacological Relevance: Rhapontici Radix ethanol extract (RRE) is derived from the dried root of Rhaponticum uniflorum (L.) DC belonging to the Asteraceae family. RRE exhibits significant anti-inflammatory and antioxidant properties; however, the potential of RRE in mastitis treatment requires further investigation., Aim of This Study: This research was performed to examine the protective properties of RRE against mastitis and the mechanisms underlying the effects of RRE., Material and Methods: RRE components were analyzed by HPLC-MS/MS and DPPH methods. Isochlorogenic acid B (ICAB) was obtained commercially. MTT assay was utilized to assess RRE or ICAB cytotoxicity in bovine mammary alveolar (MAC-T) cells. Immunohistochemistry were used to investigate the pathological alterations in mammary tissue. The protein levels of inflammatory cytokines and mediators were analyzed using ELISA, and the expression of MAPK and NF-κB signaling pathways, as well as p65 nuclear translocation, were analyzed through Western blotting and immunofluorescence techniques, respectively. Target proteins of RRE were screened by RNA-seq and tandem mass tag analyses. Protein interaction was revealed and confirmed using co-immunoprecipitation and CRISPR/Cas9-based knockdown and overexpression of target genes., Results: ICAB was revealed as one of the main components in RRE, and it was responsible for 84.33% of RRE radical scavenging activity. Both RRE and ICAB mitigated the infiltration of T lymphocytes in the mammary glands of mice, leading to decreased levels of inflammatory mediators (COX-2 and iNOS) and cytokines (TNF-α, IL-6, and IL-1β) in lipopolysaccharide (LPS)-induced MAC-T cells. Furthermore, RRE and ICAB suppressed the LPS-induced phosphorylation of NF-κB inhibitor and p65, thereby impeding p65 nuclear translocation in mouse mammary glands and MAC-T cells. In addition, RRE and ICAB attenuated the LPS-triggered activation of c-Jun N-terminal kinase 1/2, p38, and extracellular regulated protein kinase 1/2. Importantly, co-treated with LPS and ICAB in MAC-T cells, an upregulation of G-protein coupled receptor 161 (GPR161) and transmembrane protein 59 (TMEM59) was observed; the interact between TMEM59 and was found, leading to inhibition of NF-κB activity and inflammatory cytokine production., Conclusion: ICAB is a prominent antioxidant in RRE. RRE and ICAB reduce mammary inflammation via MAPK and NF-κB pathways and the interaction between TMEM59 and GPR161 mediates the control of ICAB in NF-κB signaling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ethylene glycol electro-oxidation reaction (EGOR) on nickel-based hydroxides (Ni(OH) 2 ) represents a promising strategy for generating value-added chemicals, i.e. formate and glycolate, and coupling water-electrolytic hydrogen production. The high product selectivity was one of the most significant area of polyols electro-oxidation process. Yet, developing Ni(OH) 2 -based EGOR electrocatalyst with highly selective product remains a challenge due to the unclear cognition about the EGOR mechanism. Herein, Mn-doped Ni(OH) 2 catalysts were utilized to investigate the EGOR mechanism. Experimental and calculation results reveal that the electronic states of e g * band play an important role in the catalytic performance and the product selectivity for EGOR. Broadening the e g * band could effectively enhance the adsorption capacity of glyoxal intermediates. On the other hand, this enhanced adsorption could lead to reduced side reactions associated with glycolate formation, simultaneously promoting the cleavage of C-C bonds. Consequently, the selectivity for formate was notably augmented by these enhancements. This work offers new insights into the regulation of catalyst electronic states for improving polyol electrocatalytic activity and product selectivity., (© 2024 Wiley-VCH GmbH.)

Reducing the level of annihilation of electrons and holes is considered to be a feasible strategy to promote piezocatalytic activities. But this strategy is only achieved through cumbersome sample preparation technologies, hindering its practical applications. Herein, we introduce a simple and efficient technique, the conventional solid-state method, to engineer a composite interfacial electric field to solve this problem, and validate it in a composite piezocatalysis composed of potassium sodium niobate ((K, Na)NbO 3 , KNN) and multiwalled carbon nanotubes (MWCNTs). The KNN-1CNT sample, a piezocatalyst doped with 1 wt % MWCNTs, shows a degradation rate ( k ) of 127 × 10 -3 min -1 for Rhodamine B (RhB) dye and a hydrogen peroxide (H 2 O 2 ) production rate of 36 μmol/h, about 27 times more than a reported ferroelectric composite piezocatalyst. The excellent piezocatalytic activities are attributed to the good crystallinity, slightly increased oxygen vacancies, and especially the optimal composite interface electric field. Therefore, our proposed method provides a paradigm for obtaining large-scale perovskite piezocatalysts with high piezocatalytic activities.

The apelin receptor (APJ) is a key player in tumour angiogenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. This study aims to elucidate the function of the apelin/APJ pathway in HCC using a multi-omics approach and identify potential therapeutic biomarkers. Differentially expressed genes related to the apelin/APJ axis were identified from bulk transcriptomics to reveal HCC-associated disparities. Single-cell and spatial transcriptomics were used to localize and analyse the function of these genes. Machine learning models were constructed to predict outcomes based on apelin/APJ expression, and experimental validation was conducted to explore the pathway's impact on HCC angiogenesis. Single cell analysis revealed an overexpression of APJ/Aplin in the endothelium. The stemness of endothelial cell (EC) with high apelin/APJ was enhanced, as well as the expression of TGFb, oxidative stresses and PI3K/AKT pathway genes. Spatial transcriptomics confirmed that EC populations with high APJ scores were enriched within the tumour. Machine learning models showed high prognostic accuracy. High APJ expression was linked to worse outcomes (p = 0.001), and AUC values were high (1 year, 3 year, 5 year) (0.95, 0.97, 0.98). Immune suppression and non-responsiveness of immune therapy were also seen in high-risk groups. The experimental validation showed that silencing apelin reduced angiogenesis (p  < 0.05), endothelial proliferation, decreased expression of ANG2, KLF2, VEGFA and lower ERK1/2 phosphorylation. Apelin may serve as a potential therapeutic target in HCC, given its role in promoting tumour angiogenesis and poor patient outcomes., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: This study aimed to evaluate and compare the effectiveness of knowledge base-optimized and unoptimized large language models (LLMs) in the field of orthopedics to explore optimization strategies for the application of LLMs in specific fields., Methods: This research constructed a specialized knowledge base using clinical guidelines from the American Academy of Orthopaedic Surgeons (AAOS) and authoritative orthopedic publications. A total of 30 orthopedic-related questions covering aspects such as anatomical knowledge, disease diagnosis, fracture classification, treatment options, and surgical techniques were input into both the knowledge base-optimized and unoptimized versions of the GPT-4, ChatGLM, and Spark LLM, with their generated responses recorded. The overall quality, accuracy, and comprehensiveness of these responses were evaluated by 3 experienced orthopedic surgeons., Results: Compared with their unoptimized LLMs, the optimized version of GPT-4 showed improvements of 15.3% in overall quality, 12.5% in accuracy, and 12.8% in comprehensiveness; ChatGLM showed improvements of 24.8%, 16.1%, and 19.6%, respectively; and Spark LLM showed improvements of 6.5%, 14.5%, and 24.7%, respectively., Conclusion: The optimization of knowledge bases significantly enhances the quality, accuracy, and comprehensiveness of the responses provided by the 3 models in the orthopedic field. Therefore, knowledge base optimization is an effective method for improving the performance of LLMs in specific fields., (© 2024. Huazhong University of Science and Technology.)

The challenges of sodium metal anodes, including formation of an unstable solid-electrolyte interphase (SEI) and uncontrolled growth of sodium dendrites during charge-discharge cycles, impact the stability and safety of sodium metal batteries. Motivated by the promising commercialization potential of sodium metal batteries, it becomes imperative to systematically explore innovative protective interlayers specifically tailored for sodium metal anodes. In this work, a NaBi x /NaV y O z hybrid and porous interfacial layer on sodium anode is successfully fabricated via pretreating sodium with bismuth vanadate. The hybrid interlayer effectively combines the advantages of sodium vanadates and alloys, raising a synergistic effect in facilitating sodium deposition kinetics and inhibiting the growth of sodium dendrites. As a result, the modified sodium electrodes (BVO-Na) can stably cycle for 2000 h at 0.5 mA cm -2 with a fixed capacity of 1 mAh cm -2 , and the BVO-Na||Na 3 V 2 (PO 4 ) 3 full cell sustains a high capacity of 94 mAh g -1 after 600 cycles at 5 C. This work demonstrates that constructing an artificial hybrid interlayer is a practical solution to obtain high performance anodes in sodium metal batteries., (© 2024 Wiley‐VCH GmbH.)

Aromatic coconut represents an exceptional variety of coconut known for its distinct and delightful flavor and aroma, both of which are highly cherished by consumers. Despite its popularity, there has been a lack of systematic research on aroma components and the associated synthetic genes. In this report, we developed the metabolite profiles of terpenoids by targeted metabolomics and obtained the expression profile of genes related to terpenoid biosynthesis by RNA-seq during different coconut fruit developmental stages. Totally, we separated 26 different terpenoids in aromatic coconut pulp, among which, geranyl acetate and (-)-isosyngene emerged as the most abundant. The integrated analysis of metabolism and RNA-seq data showed that HMGS2, HMGS3, IPI/IDI1, HMGR1, HMGR3, and CMK2 as potentially key genes involved in the synthesis of terpenoids in aromatic coconut. To validate these findings, qRT-PCR was conducted on terpenoid-related genes. These findings lay a foundation for understanding aroma formation and the molecular mechanism of terpenoids in coconut fruit., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Surface-structured engineering of hyperdoped silicon can effectively facilitate the absorption of sub-bandgap photons in pristine single-crystal silicon (sc-Si). Here, we conducted different annealing approaches of ordinary thermal annealing (OTA) and nanosecond laser annealing (NLA) on modification of titanium-hyperdoped silicon (Si:Ti) surface structure, to achieve efficient near-infrared detection. It is presented that both OTA and NLA processes can improve the crystallinity of Si:Ti samples. In detail, atomic-resolved STEM characterization illustrates that NLA treatment will further eliminate the amorphous phase on Si:Ti surface to varying degrees. While one-dimensional periodic stacking fault structure of 9R-Si phase is formed at the surface of sc-Si and embedded in the Si matrix during the OTA process, which reveals the seamless interface of 9R-Si/sc-Si along with [11¯0] direction. Due to the high sub-bandgap light absorption and good crystal structure, the Si:Ti photodetector after NLA treatment with an energy density of 2.6 J cm -2 exhibited the highest responsivity, reaching 151 mA W -1 at 1550 nm even at a low operating voltage of 1 V. We assume the performance enhancement of NLA processed Si:Ti photodetectors can be attributed to two aspects, the one is NLA can reduce the recombination of photo-generated charge carriers in amorphous surface layer by improving crystallization, and the other is that NLA process can weaken the diffusion of titanium impurities due to the extremely rapid heating and cooling rates. This study presents prospects towards surface-structured silicon in infrared light detection., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: The potential neuroprotective effects of dexmedetomidine against ketamine-induced neurotoxicity remain inconclusive. This study aims to investigate the influence of dexmedetomidine on ketamine-induced neuronal apoptosis and neurodevelopmental toxicity., Methods: In vitro experiments employed concentrations of 0.1 uM for dexmedetomidine and 50 uM for ketamine individually as well as their combination. Changes in apoptotic proteins and dendritic development in neurons were assessed after a 6-h exposure to the drugs with evaluations conducted 24 hs' post-treatment. In vivo experiments entailed intraperitoneal administration starting from postnatal Day 7 (P7) continuously for 3 days (P7-P9) using dosages of 100 mg/kg for ketamine and 1 mg/kg for dexmedetomidine alone or combined. Learning, memory and motor coordination abilities were evaluated via rotary rod tests and shuttle box experiments at P30 and P60, respectively., Results: Dexmedetomidine effectively mitigated ketamine-induced apoptosis in hippocampal neurons but did not alleviate associated dendritic developmental abnormalities. Although causing reduced motor coordination in mice, no improvement was observed with regard to this effect or reaction speed when treated with dexmedetomidine alongside ketamine., Conclusion: This study demonstrates that while dexmedetomidine can mitigate ketamine-induced neuronal apoptosis, it has limited impact on its associated neurodevelopmental toxicities., (© 2024 The Author(s). International Journal of Developmental Neuroscience published by Wiley Periodicals LLC on behalf of International Society for Developmental Neuroscience.)

The drive to enhance enzyme performance in industrial applications frequently clashes with the practical limitations of exhaustive experimental screening, underscoring the urgency for more refined and strategic methodologies in enzyme engineering. In this study, xylanase Xyl-1 was used as the model, coupling evolutionary insights with energy functions to obtain theoretical potential mutants, which were subsequently validated experimentally. We observed that mutations in the nonloop region primarily aimed at enhancing stability and also encountered selective pressure for activity. Notably, mutations in this region simultaneously boosted the Xyl-1 stability and activity, achieving a 65% success rate. Using a greedy strategy, mutant M4 was developed, achieving a 12 °C higher melting temperature and doubled activity. By integration of spectroscopy, crystallography, and quantum mechanics/molecular mechanics molecular dynamics, the mechanism behind the enhanced thermal stability of M4 was elucidated. It was determined that the activity differences between M4 and the wild type were primarily driven by dynamic factors influenced by distal mutations. In conclusion, the study emphasizes the pivotal role of evolution-based approaches in augmenting the stability and activity of the enzymes. It sheds light on the unique adaptive mechanisms employed by various structural regions of proteins and expands our understanding of the intricate relationship between distant mutations and enzyme dynamics.

Rationale and Objectives: Parkinson's disease (PD) shows small structural changes in nigrostriatal pathways, which can be sensitively captured through diffusion kurtosis imaging (DKI). However, the value of DKI and its radiomic features in the classification performance of PD still need confirmation. This study aimed to compare the diagnostic efficiency of DKI-derived kurtosis metric and its radiomic features with different machine learning models for PD classification., Materials and Methods: 75 people with PD and 80 healthy individuals had their brains scanned using DKI. These images were pre-processed and the standard atlas were non-linearly registered to them. With the labels in atlas, different brain regions in nigrostriatal pathways, including the caudate nucleus, putamen, pallidum, thalamus, and substantia nigra, were chosen as the region of interests (ROIs) to warped to the native space to measure the mean kurtosis (MK). Additionally, new radiomic features were developed for comparison. To handle the large amount of data, a statistical method called Z-score normalization and another method called LASSO regression were used to simplify the information. From this, a few most important features were chosen, and a combined score called Radscore was calculated using LASSO regression. For the comprehensive analyses, three different conventional machine learning models were then created: logistic regression (LR), support vector machine (SVM), and random forest (RF). To ensure the models were accurate, a process called 10-fold cross-validation was used, where the data were split into 10 parts for training and testing., Results: Using MK alone, the models achieved good results in correctly identifying PD in the validation set, with LR at 0.90, RF at 0.93, and SVM at 0.90. When the radiomic features were added, the models performed even better, with LR at 0.92, RF at 0.95, and SVM at 0.91. Additionally, a nomogram combining all the information was created to predict the likelihood of someone having PD, which had an AUC of 0.91., Conclusion: These findings suggest that the combination of DKI measurements and radiomic features can effectively diagnose PD by providing more detailed information about the brain's condition and the processes involved in the disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: The interaction between cancer cells and the tumor microenvironment is of critical importance in liver cancer. Jiedu Granule formula (JDF) has been shown to minimize the risk of recurrence and metastasis following liver cancer resection. Investigating the mechanism underlying the therapeutic effects of JDF can extend its field of application and develop novel treatment approaches., Methods: We established a rat liver orthotopic transplantation tumor model, and recorded the prognostic effects of JDF adjuvant therapy on the recurrence and metastasis of liver cancer. Liver and lung tissues were collected for immunofluorescence staining and H&E staining, respectively. In addition, THP-1 cells were incubated with PMA and IL-4 to induce them to differentiate into M2 macrophages. CSF-1 expression was knocked down using lentivirus to determine the function of CSF-1. Liver cancer cells were cultured with a conditioned medium (CM) or co-cultured with macrophages. Cell viability was determined using the MTT assay. The levels of CSF-1, CSF-1R, E-cadherin, N-cadherin, PI3K, AKT, and cleaved caspase-3 were detected using ELISA, Western blotting and qPCR. The ability of cells to migrate was assessed using cell scratch and transwell assays. Apoptosis was evaluated using flow cytometry., Results: The JDF treatment decreased the risk of liver cancer metastasis after surgery and the infiltration of CD206/CD68 cells in liver cancer tissue. In cell experiments, JDF showed effects in suppressing M2 macrophages activity and downregulating the expression of CSF-1 and CSF-1R. The concentration of CSF-1 in the supernatant was also lower in the JDF-treated group. Futhermore, M2-CM was found to promote cancer cell migration and epithelial-mesenchymal transition (EMT); however, these effects were weakened after administering JDF. Knocking down endogenous CSF-1 in M2 macrophages resulted in a comparable suppression of cancer cell migration and EMT. Additionally, JDF treatment inhibited activation of the PI3K/AKT pathway, thus promoting the apoptosis of M2 macrophages., Conclusions: Treatment with JDF reduced the EMT and migratory capacity of liver cancer cells, which might be attributed to the inhibition of M2 macrophage infiltration and interruption of the CSF-1/PI3K/AKT signaling pathway. This mechanism may hold significant implications for mitigating the risk of metastatic spread in the aftermath of hepatic surgery., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Iron is an essential element for the normal functioning of living organisms, but excessive iron deposition can lead to organ damage. This study aims to investigate the interaction between the endoplasmic reticulum stress signaling pathway and the PI3K/AKT/mTOR signaling pathway in liver injury induced by iron overload in chicks. Rspectively, 150 one-day-old broilers were divided into three groups and supplemented with 50 (C), 500 (E1), and 1000 (E2) mg ferrous sulfate monohydrate/kg in the basal diet. Samples were taken after continuous feeding for 14 days. The results showed that iron overload could upregulate the levels of ALT and AST. Histopathological examination revealed bleeding in the central vein of the liver accompanied by inflammatory cell infiltration. Hoechst staining showed that the iron overload group showed significant bright blue fluorescence, and ultrastructural observations showed chromatin condensation as well as mitochondrial swelling and cristae disorganization in the iron overload group. RT-qPCR and Western blot results showed that iron overload upregulated the expression of Bax, Caspase-3, Caspase-9, GRP78, GRP94, P-PERK, ATF4, eIF2α, IRE1, and ATF6, while downregulating the expression of Bcl-2 and the PI3K/AKT/mTOR pathway. XBP-1 splicing experiment showed significant splicing of XBP-1 gene after iron overload. PCA and correlation analysis suggested a potential association between endoplasmic reticulum stress, the PI3K/AKT/mTOR signaling pathway, and liver injury in chicks. In summary, iron overload can induce cell apoptosis and liver injury by affecting endoplasmic reticulum stress and the PI3K/AKT/mTOR signaling pathway., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Wide-bandgap perovskite solar cells (PSCs) toward tandem photovoltaic applications are confronted with the challenge of device thermal stability, which motivates to figure out a thorough cognition of wide-bandgap PSCs under thermal stress, using in situ atomic-resolved transmission electron microscopy (TEM) tools combing with photovoltaic performance characterizations of these devices. The in situ dynamic process of morphology-dependent defects formation at initial thermal stage and their proliferations in perovskites as the temperature increased are captured. Meanwhile, considerable iodine enables to diffuse into the hole-transport-layer along the damaged perovskite surface, which significantly degrade device performance and stability. With more intense thermal treatment, atomistic phase transition reveals the perovskite transform to PbI 2 along the topo-coherent interface of PbI 2 /perovskite. In conjunction with density functional theory calculations, a mutual inducement mechanism of perovskite surface damage and iodide diffusion is proposed to account for the structure-property nexus of wide-bandgap PSCs under thermal stress. The entire interpretation also guided to develop a thermal-stable monolithic perovskite/silicon tandem solar cell., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Purpose: Parkinson's disease (PD) involves pathological alterations that include cortical impairments at levels of region and network. However, its microstructural abnormalities remain to be further elucidated via an appropriate diffusion neuroimaging approach. This study aimed to comprehensively demonstrate the microstructural patterns of PD as mapped by diffusion kurtosis imaging (DKI)., Methods: The microstructure of grey matter in both the PD group and the matched healthy control group was quantified by a DKI metric (mean kurtosis). The intergroup difference and classification performance of global microstructural complexity were analyzed in a voxelwise manner and via a machine learning approach, respectively. The patterns of information flows were explored in terms of structural connectivity, network covariance and modular connectivity., Results: Patients with PD exhibited global microstructural impairments that served as an efficient diagnostic indicator. Disrupted structural connections between the striatum and cortices as well as between the thalamus and cortices were widely distributed in the PD group. Aberrant covariance of the striatocortical circuitry and thalamocortical circuitry was observed in patients with PD, who also showed disrupted modular connectivity within the striatum and thalamus as well as across structures of the cortex, striatum and thalamus., Conclusion: These findings verified the potential clinical application of DKI for the exploration of microstructural patterns in PD, contributing complementary imaging features that offer a deeper insight into the neurodegenerative process., Competing Interests: Declaration of competing interest The authors have no conflict of interest or competing interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Enzymatic oxygenation of various cyclic ketones into lactones via Baeyer-Villiger monooxygenases (BVMOs) could provide a promising route for synthesizing fragrances and pharmaceutical ingredients. However, unsatisfactory catalytic activity and thermostability restricted their applications in the pharmaceutical and food industries. In this study, we successfully improved the catalytic activity and thermostability of a Baeyer-Villiger monooxygenase ( Og BVMO) from Oceanicola granulosus by reshaping the binding pocket. As a result, mutant Og BVMO-Re displayed a 1.0- to 6.4-fold increase in the activity toward branched cyclic ketones tested, accompanied by a 3 °C higher melting point, and a 2-fold longer half-life time ( t 1/2 (45 °C)). Molecular dynamics simulations revealed that reshaping the binding pocket achieved strengthened motion correlation between amino acid residues, appropriate size of the substrate-binding pocket, beneficial surface characteristics, lower energy barriers, and shorter nucleophilic distance. This study well demonstrated the trade-off between the enzyme activity and thermostability by reshaping the substrate-binding pocket, paving the way for further engineering other enzymes.

Purpose: The purpose of this study was to analyze the intracerebral abnormalities of hemodynamics in patients with Parkinson's disease (PD) through arterial spin labelling (ASL) technique with multi-delay ASL (MDASL) and conventional single-delay ASL (SDASL) protocols and to verify the potential clinical application of these features for the diagnosis of PD., Materials and Methods: Perfusion data of the brain obtained using MDASL and SDASL in patients with PD were compared to those obtained in healthy control (HC) subjects. Intergroup comparisons of z-scored cerebral blood flow (zCBF), arterial transit time (zATT) and cerebral blood volume (zCBV) were performed via voxel-based analysis. Performance of these perfusion metrics were estimated using area under the receiver operating characteristic curve (AUC) and compared using Delong test., Results: A total of 47 patients with PD (29 men; 18 women; mean age, 69.0 ± 7.6 (standard deviation, [SD]) years; range: 50.0-84.0 years) and 50 HC subjects (28 men; 22 women; mean age, 70.1 ± 6.2 [SD] years; range: 50.0-93.0 years) were included. Relative to the uncorrected-zCBF map, the corrected-zCBF map further refined the distributed brain regions in the PD group versus the HC group, manifested as the extension of motor-related regions (P FWE < 0.001). Compared to the HC subjects, patients with PD had elevated zATT and zCBV in the right putamen, a shortened zATT in the superior frontal gyrus, and specific zCBV variations in the left precuneus and the right supplementary motor area (P FWE < 0.001). The corrected-zCBF (AUC, 0.90; 95% confidence interval [CI]: 0.84-0.96) showed better classification performance than uncorrected-zCBF (AUC, 0.84; 95% CI: 0.75-0.92) (P = 0.035). zCBV achieved an AUC of 0.89 (95% CI: 0.82-0.96) and zATT achieved an AUC of 0.66 (95% CI: 0.55-0.77). The integration model of hemodynamic features from MDASL provided improved performance (AUC, 0.97; 95% CI: 0.95-0.98) for the diagnosis of PD by comparison with each perfusion model (P < 0.001)., Conclusion: ASL identifies impaired hemodynamics in patients with PD including regional abnormalities of CBF, CBV and ATT, which can better be mapped with MDASL compared to SDASL. These findings provide complementary depictions of perfusion abnormalities in patients with PD and highlight the clinical feasibility of MDASL., Competing Interests: Disclosure of Interests The authors have no conflicts of interest to disclose in relation with this manuscript., (Copyright © 2024 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Chimeric antigen receptor natural killer (CAR-NK) cell therapy represents a potent approach to suppressing tumor growth because it has simultaneously inherited the specificity of CAR and the intrinsic generality of NK cells in recognizing cancer cells. However, its therapeutic potency against solid tumors is still restricted by insufficient tumor infiltration, immunosuppressive tumor microenvironments, and many other biological barriers. Motivated by the high potency of puerarin, a traditional Chinese medicine extract, in dilating tumor blood vessels, an injectable puerarin depot based on a hydrogen peroxide-responsive hydrogel comprising poly(ethylene glycol) dimethacrylate and ferrous chloride is concisely developed. Upon intratumoral fixation, the as-prepared puerarin depot (abbreviated as puerarin@PEGel) can activate nitrogen oxide production inside endothelial cells and thus dilate tumor blood vessels to relieve tumor hypoxia and reverse tumor immunosuppression. Such treatment can thus promote tumor infiltration, survival, and effector functions of customized epidermal growth factor receptor (HER1)-targeted HER1-CAR-NK cells after intravenous administration. Consequently, such puerarin@PEGel-assisted HER1-CAR-NK cell treatment exhibits superior tumor suppression efficacy toward both HER1-overexpressing MDA-MB-468 and NCI-H23 human tumor xenografts in mice without inducing obvious side effects. This study highlights a potent strategy to activate CAR-NK cells for augmented treatment of targeted solid tumors through reprogramming tumor immunosuppression., (© 2024 Wiley‐VCH GmbH.)

The post-transcriptional regulation of mRNA is a crucial component of gene expression. The disruption of this process has detrimental effects on the normal development and gives rise to various diseases. Searching for novel post-transcriptional regulators and exploring their roles are essential for understanding development and disease. Through a multimodal analysis of red blood cell trait genome-wide association studies (GWAS) and transcriptomes of erythropoiesis, we identify FAM46C, a non-canonical RNA poly(A) polymerase, as a necessary factor for proper red blood cell development. FAM46C is highly expressed in the late stages of the erythroid lineage, and its developmental upregulation is controlled by an erythroid-specific enhancer. We demonstrate that FAM46C stabilizes mRNA and regulates erythroid differentiation in a polymerase activity-dependent manner. Furthermore, we identify transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C, which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox homeostasis. In conclusion, our study unveils a unique role of FAM46C in positively regulating lysosome and mitochondria components, thereby promoting erythropoiesis., Competing Interests: Conflict of interest The authors declare no conflict of interests., (Copyright © 2024 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Genome-wide association studies have identified many single nucleotide polymorphisms (SNPs) associated with erythrocyte traits. However, the functional variants and their working mechanisms remain largely unknown. Here, we reported that the SNP of rs80207740, which was associated with red blood cell (RBC) volume and hemoglobin content across populations, conferred enhancer activity to XPO7 gene via allele-differentially binding to Ikaros family zinc finger 1 (IKZF1). We showed that the region around rs80207740 was an erythroid-specific enhancer using reporter assays, and that the G-allele further enhanced activity. 3D genome evidence showed that the enhancer interacted with the XPO7 promoter, and eQTL analysis suggested that the G-allele upregulated expression of XPO7. We further showed that the rs80207740-G allele facilitated the binding of transcription factor IKZF1 in EMSA and ChIP analyses. Knockdown of IKZF1 and GATA1 resulted in decreased expression of Xpo7 in both human and mouse erythroid cells. Finally, we constructed Xpo7 knockout mouse by CRISPR/Cas9 and observed anemic phenotype with reduced volume and hemoglobin content of RBC, consistent to the effect of rs80207740 on erythrocyte traits. Overall, our study demonstrated that rs80207740 modulated erythroid indices by regulating IKZF1 binding and Xpo7 expression., (© 2024 Federation of American Societies for Experimental Biology.)

Background: The clinical application of immune checkpoint inhibitors (ICIs) is limited by their drug resistance, necessitating the development of ICI sensitizers to improve cancer immunotherapy outcomes. Huang Lian Jie Du Decoction (HLJD, Oren-gedoku-to in Japanese, Hwangryunhaedok-tang in Korean), a famous traditional Chinese medicinal prescription, has exhibited potential in the field of cancer treatment. This study aims to investigate the impact of HLJD on the efficacy of ICIs in melanoma and elucidate the underlying mechanisms., Methods: The potential synergistic effects of HLJD and ICIs were investigated on the tumor-bearing mice model of B16F10 melanoma, and the tumor infiltration of immune cells was tested by flow cytometry. The differential gene expression in tumors between HLJD and ICIs group and ICIs alone group were analyzed by RNA-seq. The effects of HLJD on oxidative stress, TLR7/8, and type I interferons (IFN-Is) signaling were further validated by immunofluorescence, PCR array, and immunochemistry in tumor tissue., Results: HLJD enhanced the anti-tumor effect of ICIs, significantly inhibited tumor growth, and prolonged the survival duration in melanoma. HLJD increased the tumor infiltration of anti-tumor immune cells, especially DCs, CD4 + T cells and CD8 + T cells. Mechanically, HLJD activated the oxidative stress and TLR7/8 signaling pathway and IFN-Is-related genes in tumors., Conclusions: HLJD enhanced the therapeutic benefits of ICIs in melanoma, through increasing reactive oxygen species (ROS), promoting the TLR7/8 pathway, and activating IFN-Is signaling, which in turn activated DCs and T cells., (© 2024. The Author(s).)

Objectives: Sanshimao (SSM) is a traditional Chinese medicine formula for advanced hepatocellular carcinoma (HCC). This study was designed to investigate the effect of SSM on HCC-induced angiogenesis and to explore the potential mechanism., Methods: The endothelial cells were cultured with HCC cells conditioned medium in the 1% oxygen atmosphere to imitate tumor hypoxia microenvironment. EA.hy926 cells migration and tubulogenesis were detected by tube formation and scratch-wound assay. The protein microarray was employed to explore SSM-targeted proteins in Huh7 cells. We also established an animal model to observe the effects of SSM on angiogenesis in vivo., Results: The data indicated that SSM reduced HCC-induced migration and tube formation of EA.hy926 cells at low dose under hypoxic conditions. These effects might be partly owing to suppression of HIF-1α-induced vascular endothelial growth factorα expression in Huh7 cells. Moreover, this inhibition was in an MKK6/P38-dependent way. Besides, Huh7 subcutaneous tumor models in nude mice further demonstrated the inhibition of SSM on tumor weight might be exerted partly by reduction of angiogenesis via blocking MKK6/P38 signaling pathways., Conclusion: SSM inhibits HCC-induced pro-angiogenesis under hypoxic conditions via suppression of MKK6/P38 signaling pathways, which is favorable for HCC tumor growth., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Identification of patients at risk for type 2 diabetes mellitus (T2DM) can not only prevent complications and reduce suffering but also ease the health care burden. While routine physical examination can provide useful information for diagnosis, manual exploration of routine physical examination records is not feasible due to the high prevalence of T2DM., Objectives: We aim to build interpretable machine learning models for T2DM diagnosis and uncover important diagnostic indicators from physical examination, including age- and sex-related indicators., Methods: In this study, we present three weighted diversity density (WDD)-based algorithms for T2DM screening that use physical examination indicators, the algorithms are highly transparent and interpretable, two of which are missing value tolerant algorithms., Patients: Regarding the dataset, we collected 43 physical examination indicator data from 11,071 cases of T2DM patients and 126,622 healthy controls at the Affiliated Hospital of Southwest Medical University. After data processing, we used a data matrix containing 16004 EHRs and 43 clinical indicators for modelling., Results: The indicators were ranked according to their model weights, and the top 25% of indicators were found to be directly or indirectly related to T2DM. We further investigated the clinical characteristics of different age and sex groups, and found that the algorithms can detect relevant indicators specific to these groups. The algorithms performed well in T2DM screening, with the highest area under the receiver operating characteristic curve (AUC) reaching 0.9185., Conclusion: This work utilized the interpretable WDD-based algorithms to construct T2DM diagnostic models based on physical examination indicators. By modeling data grouped by age and sex, we identified several predictive markers related to age and sex, uncovering characteristic differences among various groups of T2DM patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lv, Luo, Huang, Guo, Bai, Yan, Jiang, Zhang, Jing, Chen and Li.)

The realization of thermally stable Tb 3+ -doped green emission at high temperatures in solid-state lighting is still a crucial challenge. Nevertheless, the study on modulating the thermally stable luminescence at high temperatures is seldom reported. The position of the intervalence charge transfer (IVCT) energy level is used to systematically investigate the thermal quenching performance of Tb 3+ -activated green-emitting phosphors with varying concentration gradients of Gd 1- x TaO 4 : x Tb 3+ ( x = 0.1%, 0.5%, and 2%) in this study. The IVCT energy levels were determined according to the empirical formula to show a decreasing trend, consistent with the position of the IVCT energy levels measured in the excitation and diffuse reflectance spectra. Moreover, the thermal quenching performance of different wavelength excitation positions (host absorption, 4f-5d of Tb 3+ , and Tb 3+ -Ta 5+ IVCT band) is quite different. The modulation of thermal quenching performance among distinct phosphors when subjected to host excitation or IVCT excitation can be elucidated through optimal positions within the energy levels associated with IVCT. The diverse concentration gradient samples exhibit varying degrees of thermal quenching performance in the variable-temperature spectra. The fluorescence lifetimes of the samples are generally comparable but slightly lower. The quantum efficiency rapidly improves as the Tb concentration increases. The underlying mechanism governing this phenomenon is elucidated by constructing a model that encapsulates the interplay between the compensating and quenching channels, in addition to the energy conversion of Tb 3+ into Gd 3+ . The abovementioned results indicate that the dual driving scheme of the doping concentration and excitation wavelength is an effective means to regulate the thermal quenching performance of Tb-activated green-emitting tantalate phosphors.

Ardisia crenata Sims, an important ethnic medicine, is recorded in the Chinese Pharmacopoeia for treating laryngeal diseases and upper respiratory tract infections. This study aimed to evaluate the antimicrobial effect of extracts and potential antimicrobial compounds of A. crenata Sims. It was found that the roots of A. crenata Sims have a potential inhibitory effect on Candida albicans and Aspergillus flavus , with MICs of 1.56 mg/mL and 0.39 mg/mL, and the leaves of A. crenata Sims have a potential inhibitory effect on Pseudomonas aeruginosa and Staphylococcus aureus , with MICs of 3.12 mg/mL and 6.77 mg/mL, respectively. Meanwhile, five compounds including one catechin and four bergenins were obtained from roots. These components were identified on the fingerprint spectrum, representing chromatographic peaks 16, 21, 22, 23, and 25, respectively. Among these, 11- β -d-glucopyranosyl-bergenin and (-)-gallocatechin showed potential inhibition for Staphylococcus aureus and Pseudomonas aeruginosa with MIC of 0.26 and 0.33 mg/mL, respectively. The roots, stems, and leaves of A. crenata Sims are very similar in chemical composition, with large differences in content. Principal component analysis (PCA) and Hierarchical cluster analysis (HCA) showed that 16 batches of A . crenata Sims could be divided into four main production areas: Guizhou, Jiangsu, Guangxi, and Jiangxi. Furthermore, molecular docking results showed that 11- β -d-glucopyranosyl-bergenin had a better affinity for Casein lytic proteinase P (ClpP), and (-)-gallocatechin possessed a strong affinity for LasA hydrolysis protease and LasB elastase. These findings suggest catechin and bergenins from A. crenata Sims can be used as antimicrobial activity molecules.

In our work, a totally anomalous thermal quenching phenomenon of red-shifted and enhanced charge transfer state (CTS) absorption is found for the first time in LiTaO 3 : x Pr 3+ phosphors. The crystal structure, luminescent properties and the mechanism of abnormal thermal quenching were investigated in detail.

Background: Parkinson's disease (PD) has been regarded as a disconnection syndrome with functional and structural disturbances. However, as the anatomic determinants, the structural disconnections in PD have yet to be fully elucidated., Purpose: To non-invasively construct structural networks based on microstructural complexity and to further investigate their potential topological abnormalities in PD given the technical superiority of diffusion kurtosis imaging (DKI) to the quantification of microstructure., Material and Methods: The microstructural data of gray matter in both the PD group and the healthy control (HC) group were acquired using DKI. The structural networks were constructed at the group level by a covariation approach, followed by the calculation of topological properties based on graph theory and statistical comparisons between groups., Results: A total of 51 patients with PD and 50 HCs were enrolled. Individuals were matched between groups with respect to demographic characteristics ( P >0.05). The constructed structural networks in both the PD and HC groups featured small-world properties. In comparison with the HC group, the PD group exhibited significantly altered global properties, with higher normalized characteristic path lengths, clustering coefficients, local efficiency values, and characteristic path lengths and lower global efficiency values ( P <0.05). In terms of nodal centralities, extensive nodal disruptions were observed in patients with PD ( P <0.05); these disruptions were mainly distributed in the sensorimotor network, default mode network, frontal-parietal network, visual network, and subcortical network., Conclusion: These findings contribute to the technical application of DKI and the elucidation of disconnection syndrome in PD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The temperature-driven redshift of the charge transfer band (CTB) exhibits promising potential for optical temperature sensing as well as for the design of anti-thermal quenching phosphors. Therefore, it is essential to investigate the displacement mechanism in detail. In this contribution, we created LiCa 2.95 MV 3 O 12 :5%Sm 3+ (M = Mg/Zn) phosphors with considerably red-shifted CTB edges upon temperature stimulation and outstanding anti-thermal quenching behavior. To investigate this unusual behavior, gaussian fitting was performed on the excitation spectra and emission spectra at different temperatures to investigate the redshift mechanism. By averaging the peak energy of the lowest excitation and emission peaks, the zero phonon line (E zp ) indicating the electronic energy level location of the charge transfer state (CTS) shows a downward trend is obtained. As well as the energy reduction of the 1 A 2 ( 1 T 1 )- 1 B 1 ( 1 T 2 ) and 1 E( 1 T 1 )- 1 B 1 ( 1 T 2 ) absorption bands in the [VO 4 ] 3- group is observed. Therefore, the drop in the CTS electronic energy level is the dominant factor in the temperature-driven CTB redshift. Based on the redshift phenomenon and anti-thermal quenching phenomenon of CTB, the phosphor exhibited exceptional optical temperature measurement performance in all three thermometry modes of excitation intensity ratio (EIR), International Committee on Illumination (CIE) color coordinates, and fluorescence intensity ratio (FIR), demonstrating its broad application prospects in the field of optical temperature sensing as well as guiding the design of anti-thermal quenching phosphors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Layered thio- and seleno-phosphate ferroelectrics, such as CuInP 2 S 6 , are promising building blocks for next-generation nonvolatile memory devices. However, because of the low Curie point, the CuInP 2 S 6 -based memory devices suffer from poor thermal stability (<42 °C). Here, exploiting the electric field-driven phase transition in the rarely studied antiferroelectric CuCrP 2 S 6 crystals, we develop a nonvolatile memristor showing a sizable resistive-switching ratio of ~ 1000, high switching endurance up to 20,000 cycles, low cycle-to-cycle variation, and robust thermal stability up to 120 °C. The resistive switching is attributed to the ferroelectric polarization-modulated thermal emission accompanied by the Fowler-Nordheim tunneling across the interfaces. First-principles calculations reveal that the good device performances are associated with the exceptionally strong ferroelectric polarization in CuCrP 2 S 6 crystal. Furthermore, the typical biological synaptic learning rules, such as long-term potentiation/depression and spike amplitude/spike time-dependent plasticity, are also demonstrated. The results highlight the great application potential of van der Waals antiferroelectrics in high-performance synaptic devices for neuromorphic computing., (© 2023. The Author(s).)

Breast cancer is a heterogeneous disease and can be divided into several subtypes with unique prognostic and molecular characteristics. The classification of breast cancer subtypes plays an important role in the precision treatment and prognosis of breast cancer. Benefitting from the relation-aware ability of a graph convolution network (GCN), we present a multi-omics integrative method, the attention-based GCN (AGCN), for breast cancer molecular subtype classification using messenger RNA expression, copy number variation and deoxyribonucleic acid methylation multi-omics data. In the extensive comparative studies, our AGCN models outperform state-of-the-art methods under different experimental conditions and both attention mechanisms and the graph convolution subnetwork play an important role in accurate cancer subtype classification. The layer-wise relevance propagation (LRP) algorithm is used for the interpretation of model decision, which can identify patient-specific important biomarkers that are reported to be related to the occurrence and development of breast cancer. Our results highlighted the effectiveness of the GCN and attention mechanisms in multi-omics integrative analysis and the implement of the LRP algorithm can provide biologically reasonable insights into model decision., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Multiple research projects have provided evidence of the correlation between obesity and cognitive impairment. WWI, a novel metric for assessing obesity, has the potential to provide a more precise assessment of muscle and fat mass. This research aimed to investigate the association between WWI and cognitive functioning among elderly individuals residing in the United States., Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2014. Weighted multiple linear regression models, smoothed fitted curves, and generalized weighted models were employed to examine the associations between WWI and cognitive function in linear and nonlinear contexts., Results: The study included a cohort of 2,764 adult volunteers aged 60 years and older, all with complete data. Upon controlling for all potential confounding variables, our analysis revealed statistically significant negative associations between WWI and the Digit Symbol Substitution Test (DSST) score. Specifically, for each 1-unit increase in WWI, there was a corresponding loss of 3.57 points in the DSST score [-3.57 (-4.31, -2.82)]. The negative correlations between WWI with CERAD total word recall [-0.63 (-0.85, -0.40)], CERAD delayed recall [-0.19 (-0.30, -0.07)], and AFT [-0.65 (-0.94, -0.37)] were significant only in partially adjusted models., Conclusion: Higher WWI was associated with poorer cognitive function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Lv and Jiang.)

Pr 3+ -related intervalence charge transfer (IVCT) bands are a research hotspot owing to their amelioration in the luminescence thermal quenching of Pr 3+ -activated phosphors. Here, a typical IVCT band displacement strategy via a topological chemical scheme is reported to optimize the luminescence thermal quenching performance of praseodymium-doped niobo-tantalate. The substitution of Ta 5+ ions for Nb 5+ ions reduces the valence-weighted average cation optical electronegativity and increases the bond lengths of the activator (Pr 3+ ) to the ligand cations (Nb 5+ and Ta 5+ ) via adjusting the crystal structure, leading to an increase in the IVCT energy level position from 3.521 to 4.139 eV. The increase in the IVCT energy level leads to an increase in the number of electrons located in the Pr 3+ 3 P 0 energy level, which compensates for the emission of 1 D 2 during warming. Especially, the energy gap value of the IVCT band is positively correlated with the thermal quenching activation energy Δ E 2 . Δ E 2 increases, the crossover point rises, and the nonradiative transition decreases, further enhancing the Pr 3+ 1 D 2 emission. At 503 K, the 1 D 2 emission integral intensity increases from 14 to 224% relative to the 303 K original integral intensity. This IVCT band displacement strategy can be used as a scheme for designing antithermal quenching luminescence materials.

Clusterin (CLU) is a highly evolutionary conserved glycoprotein with multiple isoform-specific functions and is widely distributed in different species. Accumulated evidence has shown the prominent role of CLU in regulating several essential physiological processes, including programmed cell death, metastasis, invasion, proliferation and cell growth via regulating diverse signaling pathways to mediate cancer progression in various cancers, such as prostate, breast, lung, liver, colon, bladder and pancreatic cancer. Several studies have revealed the potential benefit of inhibiting CLU in CLU inhibition-based targeted cancer therapies in vitro, in vivo or in human, suggesting CLU is a promising therapeutic target. This review discusses the multiple functions and mechanisms of CLU in regulating tumor progression of various cancers and summarizes the inhibitors of CLU used in CLU inhibition-based targeted cancer therapies., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Further adjuvant chemotherapy treatment can provide benefits to certain patients with triple-negative breast cancer (TNBC) that fail to achieve pathological complete response (pCR) after the administration of a neoadjuvant chemotherapy (NAC) regimen. However, biomarkers suitable for identifying patients likely to experience poor prognostic outcomes after undergoing additional adjuvant chemotherapy are currently lacking. Accordingly, the present meta-analysis was conducted to explore the relationship between tumor-infiltrating lymphocytes (TILs) or TIL subtypes (CD4 + or CD8 + ) in residual tumor (RT) tissue following NAC and TNBC patient prognosis. Relevant studies published through March 2023 were identified in Pubmed, The Cochrane Library, Embase and Web of Science databases. After excluding irrelevant studies, data were extracted from the remaining reports, while study quality was analyzed with the Newcastle-Ottawa Scale. Subsequent analyses were performed with Stata 14.0 and Review Manager 5.3. In total, seven relevant studies incorporating 1,202 patients were identified, all of which were retrospective cohort studies. Pooled analyses demonstrated that those patients exhibiting higher levels of RT TIL infiltration following NAC exhibited significantly improved recurrence-free, metastasis-free and event-free survival (RFS/MFS/EFS) compared with patients with lower RT TIL infiltration levels, together with an improved distant recurrence-free interval (DRFI) [hazard ratio (HR)=0.52; 95% confidence interval (CI)=0.39-0.69; P<0.00001]. In addition, patients exhibiting high RT TIL infiltration exhibited improved overall survival (OS) and breast cancer-specific survival (BCSS; HR=0.49; 95% CI=0.38-0.65; P<0.00001). Additional subgroup analyses revealed that patients with higher TIL infiltration levels or TIL subtype (CD4 + or CD8 + ) infiltration exhibited improved RFS/MFS/EFS/DRFI as compared with patients with lower levels of overall TIL or TIL subtype (CD4 + or CD8 + ) infiltration in RT tissue (HR=0.35, 95% CI=0.20-0.59, P<0.0001; HR=0.49, 95% CI=0.33-0.71, P=0.0002). Consistently, the OS/BCSS of patients exhibiting high levels of overall TIL or TIL subtype (CD4 + or CD8 + ) infiltration was increased compared with patients with lower levels of such infiltration (HR=0.33, 95% CI=0.19-0.59, P=0.0002; HR=0.55, 95% CI=0.41-0.76, P=0.0002). These data thus demonstrate that levels of overall TIL infiltration or infiltration by CD4 + or CD8 + TILs in RT following NAC can be used as a biomarker to reliably predict prognostic outcomes in patients with TNBC, in addition to highlighting possible targets that may guide the further immunotherapeutic management of these patients., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Cao et al.)

Cinobufacini injection is commonly used in the clinical treatment of tumors and hepatitis B, but the quality is uneven. Currently, the main focus of its quality assessment is on steroids and alkaloids. Based on a previous study, we screened four peptides with high reproducibility, responsiveness, and specificity. This research was the first to develop an ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry approach for evaluating the quality of cinobufacini preparations from the peptide perspective. In this study, we have identified 230 peptides in cinobufacini injection by Q-Exactive mass spectrometry, which contains species-specific peptides. Then, we used ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry to establish a quantitative method for species-specific peptides and carried out method validation. The result revealed that four peptides were linear in a specific range, and had great reproducibility, accuracy, and stability. Eventually, we evaluated the quality of eight batches of cinobufacini injections and 26 batches of toad skins using the total content of target peptides as the criterion. The outcomes demonstrated that the quality of cinobufacini injection is generally stable and the toad skin from Shandong is of the best quality. In conclusion, the quantitative approach that focuses on peptides will offer innovative perspectives on assessing the quality of cinobufacini preparations., (© 2023 Wiley-VCH GmbH.)

Objective: To evaluate the prognostic value of common clinical inflammatory and nutritional indicators before treatment in patients with non-small cell lung cancer in the real world., Method: A total of 5,239 patients with pathologically confirmed non-small cell lung cancer from 2011 to 2018 in the Affiliated Cancer Hospital of Xinjiang Medical University were selected. Their inflammatory and nutritional indicators (RDW, PDW, NLR, LMR, NMR, PLR, SII, PNI, TP, ALB, CYRFA21-1, CEA, CA125, NSE, α1-globulin, α2-globulin, β1-globulin, β2-globulin, and γ-globulin) before treatment were collected. From the total number, 1,049 patients were randomly sampled (18 to 20% of patients each year) and used as the validation set; the remaining 4,190 patients were used as the training set. According to the eighth edition of the guidelines for the diagnosis, treatment, and stage risk stratification of lung cancer, the patients were divided into four groups: stage I/II operable, stage III operable, stage III inoperable, and stage IV. We used the X-tile software to intercept and classify the cut-off values of each index in the validation set. Univariate and multivariate Cox proportional-hazard regression were used to screen the independent risk factors affecting the prognosis of non-small cell lung cancer and establish a prognostic model for 1, 3, and 5 years. The validation set was used to verify its performance. Finally, the Kaplan-Meier curve was used to assess the survival rate, and the corresponding nomogram was established for clinical use., Results: After screening, no effective indicators were found in the stage I/II operable group. RDW and CA125 were effective indicators for the stage III operable group (cut-off values were 14.1 and 9.21, respectively, compared with the low-value group; univariate HR was 2.145 and 1.612, and multivariate HR was 1.491 and 1.691, respectively). CYRFA21-1 and CA125 were effective prognostic indicators for the stage III inoperable group (cut-off values were 10.62 and 44.10, respectively, compared with the low-value group; univariate HR was 1.744 and 1.342, and multivariate HR was 1.284 and 1.304, respectively). CYRFA21-1, CA125, NLR, and α1-globulin were effective indicators of prognosis in stage IV (cut-off values were 3.07, 69.60, 4.08, and 5.30, respectively, compared with the low-value group; univariate HR was 1.713, 1.339, 1.388, and 1.539; and multivariate HR was 1.407, 1.119, 1.191, and 1.110, respectively). The model was constructed with the best validation power in stage IV patients (C-index = 0.733, 0.749, and 0.75 at 1, 3, and 5 years, respectively)., Conclusion: For patients with stage III and IV non-small cell lung cancer, some inflammatory markers, serum tumor markers, and nutritional indicators are independent prognostic factors. Combined with the general data of patients, the constructed prognostic evaluation model has the best efficacy in patients with stage IV and can be widely used in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lv, Xu, Zou, Han and Feng.)

Sodium metal battery is supposed to be a propitious technology for high-energy storage application owing to the advantages of natural abundance and low cost. Unfortunately, the uncontrollable dendrite growth critically hampers its practical implementation. Herein, an inorganic/organic hybrid layer of NaF/CF/CC on the surface of Na foil (IOHL-Na) is designed and synthesized through the in situ reaction of polyvinylidene fluoride (PVDF) and metallic sodium. This protective layer possesses satisfactory Young's modulus, good kinetic property, and sodiophilicity, which can distinctly stabilize Na metal anode. As a result, the symmetric IOHL-Na cell achieves a lifespan of 770 h at 1 mAh cm -2 /1 mA cm -2 in carbonate electrolyte. The assembled full battery of IOHL-Na||Na 3 V 2 (PO 4 ) 3 delivers a high discharge capacity of 85 mAh g -1 at 10 C after 600 cycles under ambient temperature. Furthermore, the IOHL-Na||Na 3 V 2 (PO 4 ) 3 cell still can steadily operate at 10 C for 600 cycles at 55 °C. And when testing at an ultralow temperature of -40 °C, the full cell achieves 40 mAh g -1 at 0.5 C with a prolonged lifespan of 450 cycles. This work offers a new approach to protect the metal sodium anode without dendrite growth under wide temperatures., (© 2023 Wiley-VCH GmbH.)

Oocyte maturation arrest (OMA) refers to a rare clinical phenomenon of oocyte maturation disorder caused by abnormal meiosis, which is also one of the primary causes of female infertility. The clinical manifestations of these patients are often characterized with failure to obtain mature oocytes after repeated ovulation stimulation and/or induced in vitro maturation. To date, mutations in PATL2 , TUBB8 and TRIP13 have been demonstrated to be associated with OMA, but studies on the genetic-based factors and mechanisms of OMA are still incomplete. In this study, peripheral blood from 35 primary infertile women characterized with recurrent OMA during assisted reproductive technology (ART) were subjected to whole-exome sequencing (WES). By using Sanger sequencing and co-segregated analysis, we identified four pathogenic variants in TRIP13 . Proband 1 had a homozygous missense mutation of c.859A>G appeared on the 9th exon, which resulted in substitution of Ile287 to valine (p.Ile287Val); proband 2 had a homozygous missense mutation of c.77A>G on the 1st exon, which resulted in substitution of His26 to arginine (p.His26Arg); and proband 3 had compound heterozygous mutations of c.409G>A and c.1150A>G on the 4th and 12th exon, which resulted in the substitutions of Asp137 to asparagine (p.Asp137Asn) and Ser384 to glycine (p.Ser384Gly) in the encoded protein respectively. Three of these mutations have not been reported previously. Further, transfection of plasmids harboring the respective mutated TRIP13 in HeLa cells resulted in changes in TRIP13 expression and abnormal cell proliferation as demonstrated by western blotting and cell proliferation assay respectively. This study further summarizes the TRIP13 mutations reported previously and expands the mutation spectrum of TRIP13 pathogenic variants, thereby providing a valuable reference for further research on the pathogenic mechanism of OMA associated with TRIP13 mutations.

Next-generation secondary batteries including sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs) are considered the most promising candidates for application to large-scale energy storage systems due to their abundant, evenly distributed and cost-effective sodium/potassium raw materials. The electrochemical performance of SIBs (PIBs) significantly depends on the inherent characteristics of the cathode material. Among the wide variety of cathode materials, sodium/potassium vanadium fluorophosphate (denoted as MVPF, M = Na and K) composites are widely investigated due to their fast ion transportation and robust structure. However, their poor electron conductivity leads to low specific capacity and poor rate capacity, limiting the further application of MVPF cathodes in large-scale energy storage. Accordingly, several modification strategies have been proposed to improve the performance of MVPF such as conductive coating, morphological regulation, and heteroatomic doping, which boost the electronic conductivity of these cathodes and enhance Na (K) ion transportation. Furthermore, the development and application of MVPF cathodes in SIBs at low temperatures are also outlined. Finally, we present a brief summary of the remaining challenges and corresponding strategies for the future development of MVPF cathodes.

Background: Insufficient or disrupted sleep increases the risk of cardiovascular disease, including atherosclerosis. However, we know little about the molecular mechanisms by which sleep modulates atherogenesis. This study aimed to explore the potential role of circulating exosomes in endothelial inflammation and atherogenesis under sleep deprivation status and the molecular mechanisms involved., Methods: Circulating exosomes were isolated from the plasma of volunteers with or without sleep deprivation and mice subjected to 12-week sleep deprivation or control littermates. miRNA array was performed to determine changes in miRNA expression in circulating exosomes., Results: Although the total circulating exosome levels did not change significantly, the isolated plasma exosomes from sleep-deprived mice or human were a potent inducer of endothelial inflammation and atherogenesis. Through profiling and functional analysis of the global microRNA in the exosomes, we found miR-182-5p is a key exosomal cargo that mediates the proinflammatory effects of exosomes by upregulation of MYD88 (myeloid differentiation factor 88) and activation of NF-ĸB (nuclear factor kappa-B)/NLRP3 pathway in endothelial cells. Moreover, sleep deprivation or the reduction of melatonin directly decreased the synthesis of miR-182-5p and led to the accumulation of reactive oxygen species in small intestinal epithelium., Conclusions: The findings illustrate an important role for circulating exosomes in distant communications, suggesting a new mechanism underlying the link between sleep disorder and cardiovascular disease., Competing Interests: Disclosures None.

Background: To explore the effect and mechanism of action of miR-210 on postmenopausal osteoporosis (PMPO) in ovariectomized rats in vivo., Methods: An ovariectomized (OVX) rat model was established by ovariectomy. Tail vein injection was performed to overexpress and knock down miR-210 in OVX rats, followed by the collection of blood and femoral tissues from each group of rats. And quantitative real-time polymerase chain reaction (qRT-PCR) was applied to assess the expression level of miR-210 in femoral tissues of each group. Micro computed tomography (Micro CT) was adopted to scan the microstructure of the femoral trabecula in each group to obtain relevant data like bone mineral density (BMD), bone mineral content (BMC), trabecular bone volume fraction (BV/TV), trabecular thickness (Tb.Th), bone surface-to-volume ratio (BS/BV), and trabecular separation (Tb.Sp). ELISA was used for determining the level of bone alkaline phosphatase (BALP), amino-terminal propeptide of type I procollagen (PINP), osteocalcin (OCN), and C-terminal telopeptide of type I collagen (CTX-1) in serum; and Western blot for the protein level of Runt-related transcription factor 2 (Runx2), osteopontin (OPN), and collagen type I alpha 1 (COL1A1) in femoral tissues., Results: MiR-210 expression was significantly decreased in femoral tissues of OVX rats. Overexpression of miR-210 could obviously increase BMD, BMC, BV/TV and Tb.Th, whereas significantly decrease BS/BV and Tb.Sp in femurs of OVX rats. Moreover, miR-210 also downregulated BALP and CTX-1 level, upregulated PINP and OCN level in the serum of OVX rats promoted the expression of osteogenesis-related markers (Runx2, OPN and COL1A1) in the femur of OVX rats. Additionally, further pathway analysis revealed that high expression of miR-210 activated the vascular endothelial growth factor (VEGF)/Notch1 signaling pathway in the femur of OVX rats., Conclusion: High expression of miR-210 may improve the micromorphology of bone tissue and modulate bone formation and resorption in OVX rats by activating the VEGF/Notch1 signaling pathway, thereby alleviating osteoporosis. Consequently, miR-210 can serve as a biomarker for the diagnosis and treatment of osteoporosis in postmenopausal rats., (© 2023. The Author(s).)

Given the widely existing stability-activity trade-off in enzyme evolution, it is still a goal to obtain enzymes embracing both high activity and stability. Herein, we employed an isothermal compressibility (β T ) perturbation engineering (ICPE) strategy to comprehensively understand the stability-activity seesaw-like mechanism. The stability and activity of mutants derived from ICPE uncovered a high Pearson correlation ( r = 0.93) in a prototypical enzyme T1 lipase. The best variant A186L/L188M/A190Y exhibited a high T m value up to 78.70 °C, catalytic activity of 474.04 U/mg, and a 73.33% increase in dimethyl sulfoxide resistance compared to the wild type, one of the highest comprehensive performances reported to date. The elastic activation mechanism mediated by conformational change with a Δβ T range of -6.81 × 10 -6 to -1.90 × 10 -6 bar -1 may account for the balancing of stability and activity to achieve better performing enzymes. The ICPE strategy deepens our understanding of stability-activity trade-off and boosts its applications in enzyme engineering.

Background: Ferroptosis has been identified as a potent predictor of cancer prognosis. Currently, cervical cancer ranks among the most prevalent malignant tumors in women. Enhancing the prognosis for patients experiencing metastasis or recurrence is of critical importance. Consequently, investigating the potential of ferroptosis-related genes (FRGs) as prognostic biomarkers for cervical cancer patients is essential. Methods: In this study, 52 FRGs were obtained from the GSE9750, GSE7410, GSE63514, and FerrDb databases. Six genes possessing prognostic characteristics were identified: JUN, TSC22D3, SLC11A2, DDIT4, DUOX1, and HELLS. The multivariate Cox regression analysis was employed to establish and validate the prognostic model, while simultaneously performing a correlation analysis of the immune microenvironment. Results: The prediction model was validated using TCGA-CESC and GSE44001 datasets. Furthermore, the prognostic model was validated in endometrial cancer and ovarian serous cystadenocarcinoma cases. KM curves revealed significant differences in OS between high-risk and low-risk groups. ROC curves demonstrated the stability and accuracy of the prognostic model established in this study. Concurrently, the research identified a higher proportion of immune cells in patients within the low-risk group. Additionally, the expression of immune checkpoints (TIGIT, CTLA4, BTLA, CD27, and CD28) was elevated in the low-risk group. Ultimately, 4 FRGs in cervical cancer were corroborated through qRT-PCR. Conclusion: The FRGs prognostic model for cervical cancer not only exhibits robust stability and accuracy in predicting the prognosis of cervical cancer patients but also demonstrates considerable prognostic value in other gynecological tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Han, Wang, Lv, Li and Feng.)

Objectives: Isoflurane (ISO) is widely used in the clinic and research. The authors aimed to explore whether Neobaicalein (Neob) could protect neonatal mice from ISO-induced cognitive damage., Method: The open field test, Morris water maze test, and tail suspension test was performed to assess the cognitive function in mice. Enzyme-linked immunosorbent assay was used to evaluate inflammatory-related protein concentrations. Immunohistochemistry was used to assess Ionized calcium-Binding Adapter molecule-1 (IBA-1) expression. Hippocampal neuron viability was detected using the Cell Counting Kit-8 assay. Double immunofluorescence staining was employed to confirm the interaction between proteins. Western blotting was used to assess protein expression levels., Results: Neob notably improved cognitive function and exhibited anti-inflammatory effects; moreover, under iso-treatment, it exhibited neuroprotective effects. Furthermore, Neob suppressed interleukin-1β, tumor necrosis factor-α, and interleukin-6 levels and upregulated interleukin-10 levels in ISO-treated mice. Neob significantly mitigated iso-induced increases in IBA-1-positive cell numbers of the hippocampus in neonatal mice. Furthermore, it inhibited ISO-induced neuronal apoptosis. Mechanistically, Neob was observed to upregulate cAMP Response Element Binding protein (CREB1) phosphorylation and protected hippocampal neurons from ISO-mediated apoptosis. Moreover, it rescued ISO-induced abnormalities of synaptic protein., Conclusions: Neob prevented ISO anesthesia-induced cognitive impairment by suppressing apoptosis and inflammation through upregulating CREB1., Competing Interests: Conflicts of interest The authors declare no have conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Transglutaminase 2 (TGM2) is a versatile enzyme that modulates cell survival and differentiation. However, its role in terminal erythroid differentiation is poorly understood. In this study, we investigated the function of TGM2 in primary fetal liver erythroid differentiation. We predicted TGM2 as an upstream regulator via ingenuity pathway analysis (IPA), and found that its expression was increased at both RNA and protein level during terminal erythroid differentiation. TGM2 cross-linking activity inhibitors GK921 and Z-DON suppressed erythroid maturation and enucleation, while its GTPase inhibitor LDN27219 had no such effect. Z-DON treatment arrested differentiation at basophilic erythroblast stage, and interfered with cell cycle progression. RT-PCR demonstrated decreased GATA-1 and KLF1, and disarranged cyclin, CDKI and E2F family genes expression after Z-DON treatment. In conclusion, TGM2 regulates terminal erythroid differentiation through its cross-linking enzyme activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Shi, Yang, Liu and Lv.)

Background: Severe mouth opening difficulty may increase the risk of airway management during anesthesia induction, and awake fiberoptic nasotracheal intubation (AFNI) is the first option for patients with orofacial anatomical changes., Case Summary: A 54-year-old man was scheduled to undergo wedge resection of the right upper lung in August 2021. The patient had a history of enlarged right maxillary lesion resection and partial right maxillary resection surgery in April 2020, which led to orofacial anatomical changes and severe mouth opening difficulty. To avoid difficult airway-related emergency scenarios, the AFNI was successfully performed through intravenous injection of sufentanil and dexmedetomidine combined with lidocaine topical anesthesia under a conscious state without any uncomfortable feeling or complications., Conclusions: Intravenous injection of sufentanil and dexmedetomidine combined with lidocaine topical anesthesia can be used as an alternative medication scheme to relieve uncomfortable suffering for AFNI in patients with severe mouth opening difficulty., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The use of efficient and clean methods for the recycling of waste circuit boards is an ongoing challenge. In this research, the effect of microwave pretreatment on the leaching and enrichment of copper from waste print circuit board (WPCB) was studied. The morphology and chemical structure of WPCB particles before and after microwave pretreatment were analyzed by SEM/EDS and Fourier infrared spectroscopy. Leaching experiments and copper enrichment tests were designed to investigate the effect of different microwave irradiation powers and microwave irradiation times on the copper leaching rate and copper enrichment rate in WPCB. The leaching experiment results showed that microwave pretreatment can effectively improve the leaching rate of WPCB. When the microwave irradiation power was 700 W, the irradiation time was 120 s, and the leaching time was 15 min, the copper leaching rate in WPCB was 57.01%, which was 24.34% higher than that in the untreated condition. The results of copper enrichment experiment show that microwave pretreatment can effectively improve the copper enrichment of WPCB. After microwave pretreatment, copper was effectively enriched in the 4-2 and 2-1 mm particle sizes. When the microwave irradiation time was 120 s, the copper enrichment rates in the 4-2 and 2-1 mm particle sizes were 1.74 and 1.66, which increased by 0.63 and 0.32, respectively, compared to the untreated condition. Microwave pretreatment enables the effective separation of metallic copper from non-metallic components in WPCB, increasing the exposure area of copper and promoting the monomer separation of copper, thus improving the leaching and enrichment of copper., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Chromodomain helicase DNA binding protein 4 (CHD4), as a core component of the nucleosome remodeling and deactetylase (NuRD) complex, participated in the inititation and development of myriad cancers. However, little is known about the linkage between CHD4 and breast cancer stemness. Here, we found that CHD4 repress the expression of SOX2, a key regulator of cancer stem cells (CSCs), to suppress cancer stemness in breast cancer. Mechanistically, CHD4 binds to the promoter of SOX2 depend on TRPS1. And CHD4 transcriptional activation of SOX2 was abolished by TRPS1. These findings identify CHD4 as a regulator of SOX2 linked to breast cancer stemness and provide detailed mechanistic of CHD4 in CSC functions., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)