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Injectable hydrogels are promising for treatment of bone defects in clinic owing to their minimally invasive procedure. Currently, there is limited emphasis on how to utilize injectable hydrogels to mobilize body's regenerative potential for enhancing bone regeneration. Herein, an injectable bone-mimicking hydrogel (BMH) scaffold assembled from nanocomposite microgel building blocks was developed, in which a highly interconnected microporous structure and an inorganic/organic (methacrylated hydroxyapatite and methacrylated gelatin) interweaved nano structure were well-designed. Compared with hydrogels lacking micro-nano structures or only showing microporous structure, the BMH scaffold enhanced the ingrowth of vessels and promoted the formation of dense cellular networks (including stem cells and M2 macrophages), across the entire scaffold at early stage after subcutaneous implantation. Moreover, the BMH scaffold could not only directly trigger osteogenic differentiation of the infiltrated stem cells, but also provided an instructive osteo-immune microenvironment by inducing macrophages into M2 phenotype. Mechanistically, our results reveal that the nano-rough structure of the BMH plays an essential role in inducing macrophage M2 polarization through activating mechanotransduction related RhoA/ROCK2 pathway. Overall, this work offers an injectable hydrogel with micro-nano structure driven bio-responsive abilities, highlighting harnessing body's inherent regenerative potential to realize bone regeneration., 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 Ltd. All rights reserved.)

Food allergy is one of the hot issues in the field of food safety, and there have been a lot of concerns on how to reduce the allergenicity of food allergens. Food processing can change the allergenicity of allergens in the food matrix. In this study, ten IgE linear epitopes of the major allergen tropomyosin (TM) in Perna viridis were identified by bioinformatics prediction and serological experiments. The transglutaminase-catalyzed glycosylation modification sites glutamine, lysine and arginine were highly represented in the IgE linear epitopes of TM. The Perna viridis food matrix was treated with transglutaminase-catalyzed glycosylation. This reaction changed the secondary structure of protein in the food matrix, increased the content of β-sheets and decreased the content of β-turns. The intensity of intrinsic fluorescence and surface hydrophobicity were reduced. The IgE-binding activity of TM in the food matrix was reduced by modifying seven amino acid residues on six IgE linear epitopes. Transglutaminase-catalyzed glycosylation products decreased allergic symptoms in allergic mice, reduced the proportion of CD4 + IL-4 + Th2 cells, and increased the proportion of CD4 + IFN-γ + Th1 cells and Treg cells. Mouse serum levels of IgE and IgG1 antibodies in the food matrix and TM were reduced. Therefore, this study provided a theoretical basis for the development of hypoallergenic Perna viridis products.

Purpose of Review: Our work is to establish more distinct association between specific stress and vascular smooth muscle cells (VSMCs) phenotypes to alleviate atherosclerotic plaque burden and delay atherosclerosis (AS) progression., Recent Finding: In recent years, VSMCs phenotypic transition has received significant interests. Different stresses were found to be associated with VSMCs phenotypic transition. However, the explicit correlation between VSMCs phenotype and specific stress has not been elucidated clearly yet. We discover that VSMCs phenotypic transition, which is widely involved in the progression of AS, is associated with specific stress. We discuss approaches targeting stresses to intervene VSMCs phenotypic transition, which may contribute to develop innovative therapies for AS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The adzuki bean is a typical short-day plant and an important grain crop that is widely used due to its high nutritional and medicinal value. The adzuki bean flowering time is affected by multiple environmental factors, particularly the photoperiod. Adjusting the day length can induce flower synchronization in adzuki bean and accelerate the breeding process. In this study, we used RNA sequencing analysis to determine the effects of different day lengths on gene expression and metabolic characteristics related to adzuki bean flowering time., Methods: 'Tangshan hong xiao dou' was used as the experimental material in this study and field experiments were conducted in 2022 using a randomized block design with three treatments: short-day induction periods of 5 d (SD-5d), 10 d (SD-10d), and 15 d (SD-15d)., Results: A total of 5,939 differentially expressed genes (DEGs) were identified, of which 38.09% were up-regulated and 23.81% were down-regulated. Gene ontology enrichment analysis was performed on the target genes to identify common functions related to photosystems I and II. Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified two pathways involved in the antenna protein and circadian rhythm. Furthermore, florescence was promoted by down-regulating genes in the circadian rhythm pathway through the blue light metabolic pathway; whereas, antenna proteins promoted flowering by enhancing the reception of light signals and accelerating electron transport. In these two metabolic pathways, the number of DEGs was the greatest between the SD-5d VS SD-15d groups. Real-time reverse transcription‒quantitative polymerase chain reaction analysis results of eight DEGs were consistent with the sequencing results. Thus, the sequencing results were accurate and reliable and eight genes were identified as candidates for the regulation of short-day induction at the adzuki bean seedling stage., Conclusions: Short-day induction was able to down-regulate the expression of genes related to flowering according to the circadian rhythm and up-regulate the expression of certain genes in the antenna protein pathway. The results provide a theoretical reference for the molecular mechanism of short-day induction and multi-level information for future functional studies to verify the key genes regulating adzuki bean flowering., Competing Interests: The authors declare that they have no competing interests., (© 2024 Dong et al.)

Objective: To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ)., Methods: Clinical data of three children diagnosed with late-onset MADD at the Children's Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years., Results: The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c.1211T>C (p.M404T) and a maternal c.488-22T>G variant in child 1, a paternal c.1717C>T (p.Q573X) and a maternal c.250G>A (p.A84T) variant in child 2, and a paternal c.1285+1G>A and maternal c.629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B 2 , levocarnitine and coenzyme Q10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up., Conclusion: The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.

- Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a life-threatening condition marked by severe lung inflammation and increased lung endothelial barrier permeability. Endothelial glycocalyx deterioration is the primary factor of vascular permeability changes in ARDS/ALI. Although previous studies have shown that phospholipase D2 (PLD2) is closely related to the onset and progression of ARDS/ALI, its role and mechanism in the damage of endothelial cell glycocalyx remains unclear. We used LPS-induced ARDS/ALI mice (in vivo) and LPS-stimulated injury models of EA.hy926 endothelial cells (in vitro). We employed C57BL/6 mice, including wild-type and PLD2 knockout (PLD2 -/- ) mice, to establish the ARDS/ALI model. We applied immunofluorescence and ELISA to examine changes in syndecan-1 (SDC-1), matrix metalloproteinase-9 (MMP9), inflammatory cytokines (TNF-α, IL-6, and IL-1β) levels and the effect of external factors, such as phosphatidic acid (PA), 1-butanol (a PLD inhibitor), on SDC-1 and MMP9 expression levels. We found that PLD2 deficiency inhibits SDC-1 degradation and MMP9 expression in LPS-induced ARDS/ALI. Externally added PA decreases SDC-1 levels and increases MMP9 in endothelial cells, hence underlining PA's role in SDC-1 degradation. Additionally, PLD2 deficiency decreases the production of inflammatory cytokines (TNF-α, IL-6, and IL-1β) in LPS-induced ARDS/ALI. In summary, these findings suggest that PLD2 deficiency plays a role in inhibiting the inflammatory process and protecting against endothelial glycocalyx injury in LPS-induced ARDS/ALI., 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. Published by Elsevier Inc.)

Sodium-ion batteries (SIBs) have significant potential for applications in portable electric vehicles and intermittent renewable energy storage due to their relatively low cost. Currently, hard carbon (HC) materials are considered commercially viable anode materials for SIBs due to their advantages, including larger capacity, low cost, low operating voltage, and inimitable microstructure. Among these materials, renewable biomass-derived hard carbon anodes are commonly used in SIBs. However, the reports about biomass hard carbon from basic research to industrial applications are very rare. In this paper, we focus on the research progress of biomass-derived hard carbon materials from the following perspectives: (1) sodium storage mechanisms in hard carbon; (2) optimization strategies for hard carbon materials encompassing design, synthesis, heteroatom doping, material compounding, electrolyte modulation, and presodiation; (3) classification of different biomass-derived hard carbon materials based on precursor source, a comparison of their properties, and a discussion on the effects of different biomass sources on hard carbon material properties; (4) challenges and strategies for practical of biomass-derived hard carbon anode in SIBs; and (5) an overview of the current industrialization of biomass-derived hard carbon anodes. Finally, we present the challenges, strategies, and prospects for the future development of biomass-derived hard carbon materials.

Bainong sterility (BNS) is a thermo-sensitive genic male sterile wheat line, characterised by anther fertility transformation in response to low temperature (LT) stress during meiosis, the failure of vacuole decomposition and the absence of starch accumulation in sterile bicellular pollen. Our study demonstrates that the late microspore (LM) stage marks the transition from the anther growth to anther maturation phase, characterised by the changes in anther structure, carbohydrate metabolism and the main transport pathway of sucrose (Suc). Fructan is a main storage polysaccharide in wheat anther, and its synthesis and remobilisation are crucial for anther development. Moreover, the process of pollen amylogenesis and the fate of the large vacuole in pollen are closely intertwined with fructan synthesis and remobilisation. LT disrupts the normal physiological metabolism of BNS anthers during meiosis, particularly affecting carbohydrate metabolism, thus determining the fate of male gametophytes and pollen abortion. Disruption of fructan synthesis and remobilisation regulation serves as a decisive event that results in anther abortion. Sterile pollen exhibits common traits of pollen starvation and impaired starch accumulation due to the inhibition of apoplastic transport starting from the LM stage, which is regulated by cell wall invertase TaIVR1 and Suc transporter TaSUT1., (© 2024 John Wiley & Sons Ltd.)

Electronic stethoscope used to detect cardiac sounds that contain essential clinical information is a primary tool for diagnosis of various cardiac disorders. However, the linear electromechanical constitutive relation makes conventional piezoelectric sensors rather ineffective to detect low-intensity, low-frequency heart acoustic signal without the assistance of complex filtering and amplification circuits. Herein, it is found that triboelectric sensor features superior advantages over piezoelectric one for microquantity sensing originated from the fast saturated constitutive characteristic. As a result, the triboelectric sensor shows ultrahigh sensitivity (1215 mV Pa -1 ) than the piezoelectric counterpart (21 mV Pa -1 ) in the sound pressure range of 50-80 dB under the same testing condition. By designing a trumpet-shaped auscultatory cavity with a power function cross-section to achieve acoustic energy converging and impedance matching, triboelectric stethoscope delivers 36 dB signal-to-noise ratio for human test (2.3 times of that for piezoelectric one). Further combining with machine learning, five cardiac states can be diagnosed at 97% accuracy. In general, the triboelectric sensor is distinctly unique in basic mechanism, provides a novel design concept for sensing micromechanical quantities, and presents significant potential for application in cardiac sounds sensing and disease diagnosis., (© 2024 Wiley‐VCH GmbH.)

Background: Postmenopausal osteoporosis (PMOP) is a systemic bone disease characterized by low bone mass and microstructural damage. Morinda Officinalis (MO) contains various components with anti-PMOP activities. Morinda Officinalis-derived extracellular vesicle-like particles (MOEVLPs) are new active components isolated from MO, and no relevant studies have investigated their anti-osteoporosis effect and mechanism., Purpose: To investigate the alleviating effect of MOEVLPs on PMOP and the underlying mechanism., Methods: Differential centrifugation and ultracentrifugation were used to isolate MOEVLPs from MO. Transmission electron microscopy (TEM), flow nano analyzer, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), agarose gel electrophoresis, and thin-layer chromatography were employed to characterize MOEVLPs. PMOP mouse models were utilized to examine the anti-PMOP effect of MOEVLPs. H&E and immunohistochemical staining were used for drug safety and osteogenic effect assessment. Mouse embryo osteoblast precursor cells (MC3T3-E1) were used in vitro experiments. CCK-8 kit, alizarin red staining, proteomic, bioinformatic analyses, and western blot were used to explore the mechanism of MOEVLPs., Results: In this study, MOEVLPs from MO were successfully isolated and characterized. Animal experiments demonstrated that MOEVLPs exhibited specific femur targeting, were non-toxic to the heart, liver, spleen, lung, kidney, and aorta, and possessed anti-PMOP properties. The ability of MOEVLPs to strengthen bone formation was better than that of alendronate. In vitro experiments, results revealed that MOEVLPs did not significantly enhance osteogenic differentiation in MC3T3-E1 cells. Instead, MOEVLPs promoted the proliferation of MC3T3-E1 cells. Proteomic and bioinformatic analyses suggested that the proliferative effect of MOEVLPs was closely associated with the mitogen-activated protein kinase (MAPK) signaling pathway, particularly the altered expression of cAMP response element-binding protein (CREB) and ribosomal S6 kinase 1 (RSK1). Western blot results further confirmed these findings., Conclusion: Our studies successfully isolated high-quality MOEVLPs and demonstrated that MOEVLPs can alleviate PMOP by promoting osteoblast proliferation through the MAPK pathway. MOEVLPs have the potential to become a novel and natural anti-PMOP drug., 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. Published by Elsevier GmbH.)

Background: Estimated pulse wave velocity (ePWV) has been found to be an independent predictor of cardiovascular mortality and kidney injury, which can be estimated noninvasively. This study aimed to investigate the association between ePWV and in-hospital mortality in critically ill patients with acute kidney injury (AKI)., Methods: This study included 5960 patients with AKI from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The low and high ePWV groups were compared using a Kaplan-Meier survival curve to evaluate the differences in survival status. Cox proportional hazards models were used to explore the association between ePWV and in-hospital mortality in critically ill patients with AKI. To further examine the dose-response relationship, we used a restricted cubic spline (RCS) model. Stratification analyses were conducted to investigate the effect of ePWV on hospital mortality across various subgroups., Results: Survival analysis indicated that patients with high ePWV had a lower survival rate than those with low ePWV. Following adjustment, high ePWV demonstrated a statistically significant association with an increased risk of in-hospital mortality among AKI patients (HR = 1.53, 95% CI = 1.36-1.71, p  < 0.001). Analysis using the RCS model confirmed a linear increase in the risk of hospital mortality as the ePWV values increased ( P for nonlinearity = 0.602)., Conclusions: A high ePWV was significantly associated with an increased risk of in-hospital mortality among patients with AKI. Furthermore, ePWV was an independent predictor of in-hospital mortality in critically ill patients with AKI.

Exocytosis of a single cell has been extensively researched in recent years due to its close association with numerous diseases. However, current methods only investigate exocytosis at either the single-cell or multiple-cell level, and a method for simultaneously studying exocytosis at both levels has yet to be established. In this study, a combined device incorporating ultramicroelectrode (UME) electrochemistry and surface plasmon resonance (SPR) was developed, enabling the simultaneous monitoring of single-cell and multiple-cell exocytosis. PC12 cells were cultured directly on the SPR sensing Au film, with a carboxylated carbon nanopipette (c-CNP) electrode employed for electrochemical detection in the SPR reaction cell. Upon exocytosis, the released dopamine diffuses onto the inner wall of c-CNP, undergoing an electrochemical reaction to generate a current peak. Concurrently, exocytosis can also induce changes in the refractive index of the Au film surface, leading to the SPR signal. Consequently, the device enables real-time monitoring of exocytosis from both single and multiple cells with a high spatiotemporal resolution. The c-CNP electrode exhibited excellent resistance to protein contamination, high sensitivity for dopamine detection, and the capability to continuously monitor dopamine exocytosis over an extended period. Analysis of both SPR and electrochemical signals revealed a positive correlation between changes in the SPR signal and the frequency of exocytosis. This study introduces a novel method and platform for the simultaneous investigation of single-cell and multiple-cell exocytosis.

The cell wall is the major interface for arbuscular mycorrhizal (AM) symbiosis. However, the roles of cell wall proteins and cell wall synthesis in AM symbiosis remain unclear. We reported that a novel wall-associated kinase 13 (GhWAK13) positively regulates AM symbiosis and negatively regulates Verticillium wilt resistance in cotton. GhWAK13 transcription was induced by AM symbiosis and Verticillium dahliae (VD) infection. GhWAK13 is located in the plasma membrane and expressed in the arbuscule-containing cortical cells of mycorrhizal cotton roots. GhWAK13 silencing inhibited AM colonization and repressed gene expression of the mycorrhizal pathway. Moreover, GhWAK13 silencing improved Verticillium wilt resistance and triggered the expression of immunity genes. Therefore, GhWAK13 is considered an immune suppressor required for AM symbiosis and disease resistance. GhWAK7A, a positive regulator of Verticillium wilt resistance, was upregulated in GhWAK13-silenced cotton plants. Silencing GhWAK7A improved AM symbiosis. Oligogalacturonides application also suppressed AM symbiosis. Finally, GhWAK13 negatively affected the cellulose content by regulating the transcription of cellulose synthase genes. The results of this study suggest that immunity suppresses AM symbiosis in cotton. GhWAK13 affects AM symbiosis by suppressing immune responses., (© 2023 The Authors. New Phytologist © 2023 New Phytologist Foundation.)

The treatment of full-thickness skin injuries complicated by severe infection is hampered by the lack of comprehensive solutions that can regulate the various stages of wound healing. Consequently, there is an urgent need for a multifunctional dressing capable of multi-level regulation. In this study, we propose a novel solution by covalently integrating ε-poly-l-lysine-grafted gallic acid (EG) and in situ bioreduced silver nanoparticles (AgNPs) onto nano-hydroxyapatite (nHAP), thereby developing a multi-layered, multifunctional nanoplatform (nHEA). Cell experiments have shown that, compared to nHAP and nHAP loaded only with EG (nHEG), the addition of AgNPs to nHEA confers excellent antibacterial properties while maintaining optimal biocompatibility. The incorporation of EG onto nHEG and nHEA imparts antioxidation, anti-inflammatory, and pro-angiogenic functions, and the release of Ca 2+ and EG further enhances fibroblast migration and collagen secretion. In a rat model of full-thickness skin injury with severe infection, nHEA demonstrates remarkable antibacterial and anti-inflammatory effects, along with promoting collagen remodeling and regeneration. Together, both cell experiments and animal studies confirm the significant potential of this innovative multifunctional nanoplatform in the treatment of full-thickness skin injuries with severe infection. STATEMENT OF SIGNIFICANCE: Treating infected full-thickness skin injuries poses a longstanding challenge due to the lack of comprehensive solutions that can regulate different stages of wound healing. This study introduces a novel multifunctional nanoplatform, nHEA, developed by covalently integrating ε-poly-l-lysine grafted with gallic acid (EG) and in situ bioreduced AgNPs onto nano-hydroxyapatite (nHAP). Cell experiments reveal that the integration of AgNPs enhances nHEA's antibacterial performance while maintaining optimal biocompatibility. The inclusion of EG bestows antioxidant, inflammation-regulating, and angiogenetic properties upon nHEA, and the release of Ca 2+ and EG stimulates the migration and collagen secretion of fibroblast cells. Consequently, nHEA exhibits superior antibacterial and inflammation-regulating efficacy, and stimulates collagen remodeling and regeneration in vivo, making it a promising treatment for severely infected skin injuries., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Surface plasmons have proven their ability to boost the sensitivity of mid-infrared hyperspectral imaging by enhancing light-matter interactions. Surface phonons, a counterpart technology to plasmons, present unclear contributions to hyperspectral imaging. Here, we investigate this by developing a plasmon-phonon hyperspectral imaging system that uses asymmetric cross-shaped nanoantennas composed of stacked plasmon-phonon materials. The phonon modes within this system, controlled by light polarization, capture molecular refractive index intensity and lineshape features, distinct from those observed with plasmons, enabling more precise and sensitive molecule identification. In a deep learning-assisted imaging demonstration of severe acute respiratory syndrome coronavirus (SARS-CoV), phonons exhibit enhanced identification capabilities (230,400 spectra/s), facilitating the de-overlapping and observation of the spatial distribution of two mixed SARS-CoV spike proteins. In addition, the plasmon-phonon system demonstrates increased identification accuracy (93%), heightened sensitivity, and enhanced detection limits (down to molecule monolayers). These findings extend phonon polaritonics to hyperspectral imaging, promising applications in imaging-guided molecule screening and pharmaceutical analysis.

The utilization of Microelectromechanical Systems (MEMS) technology holds great significance for developing compact and high-performance humidity sensors in human healthcare, and the Internet of Things. However, several drawbacks of the current MEMS humidity sensors limit their applications, including their long response time, low sensitivity, relatively large sensing area, and incompatibility with a complementary metal-oxide-semiconductor (CMOS) process. To address these problems, a suspended aluminum scandium nitride (AlScN) Lamb wave humidity sensor utilizing a graphene oxide (GO) layer is firstly designed and fabricated. The theoretical and experimental results both show that the AlScN Lamb wave humidity sensor exhibits high sensing performance. The mass loading sensitivity of the sensor is one order higher than that of the normal surface acoustic wave (SAW) humidity sensor based on an aluminum nitride (AlN) film; thus the AlScN Lamb wave humidity sensor achieves high sensitivity (∼41.2 ppm per % RH) with only an 80 nm-thick GO film. In particular, the as-prepared suspended AlScN Lamb wave sensors are able to respond to the wide relative humidity (0-80% RH) change in 2 s, and the device size is ultra-compact (260 μm × 72 μm). Moreover, the sensor has an excellent linear response in the 0-80% RH range, great repeatability and long-term stability. Therefore, this work brings opportunities for the development of ultra-compact and high-performance humidity sensors.

Objective: Kisspeptin, a protein encoded by the KISS1 gene, functions as an essential factor in suppressing tumor growth. The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway, which assumes a central role in maintaining cellular homeostasis. In the specific context of this investigation, the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization. This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway, aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion (RSA)., Methods: We enrolled a cohort comprising 45 individuals diagnosed with RSA, who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020. On the other hand, an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included. To comprehensively assess the molecular landscape, Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin (and its gene KISS1 ), IGFBP1 (an established marker of decidualization), Notch1, Akt, and Foxo1 within the decidua. Human endometrial stromal cells (hESC) were given targeted interventions, including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10 (the bioactive fragment of kisspeptin), and were subsequently designated as the siKP group or the KP10 group, respectively. A control group comprised hESC was transfected with blank siRNA, and cell proliferation was meticulously evaluated with CCK8 assay. Following in vitro induction for decidualization across the three experimental groups, immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups. Furthermore, RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1, Notch1, Akt, and Foxo1 across the three cell groups. Subsequently, decidualization was induced in hESC by adding inhibitors targeting Notch1, Akt, and Foxo1. The expression profiles of the aforementioned proteins and genes in the four groups were then examined, with hESC induced for decidualization without adding inhibitors serving as the normal control group. To establish murine models of normal pregnancy (NP) and RSA, CBA/J×BALB/c and CBA/J×DBA/2 mice were used. The mice were respectively labeled as the NP model and RSA model. The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234 (acting as a blocker) and were designated as RSA-KP10 and NP-KP234 groups. On the other hand, the control groups received intraperitoneal injections of normal saline (NS) and were referred to as RSA-NS and NP-NS groups. Each group comprised 6 mice, and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes., Results: The analysis revealed that the expression levels of kisspeptin, IGFBP1, Notch1, Akt, and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP ( P <0.01 for kisspeptin and P <0.05 for IGFBP1, Notch1, Akt, and Foxo1). After the introduction of kisspeptin10 to hESC, there was an observed enhancement in decidualization capability. Subsequently, the expression levels of Notch1, Akt, and Foxo1 showed an increase, but they decreased after interference with KISS1 . Through immunofluorescence analysis, it was observed that proliferative hESC displayed a slender morphology, but they transitioned to a rounder and larger morphology post-decidualization. Concurrently, the expression of Notch1 increased, suggesting enhanced decidualization upon the administration of kisspeptin10, but the expression decreased after interference with KISS1 . Further experimentation involved treating hESC with inhibitors specific to Notch1, Akt, and Foxo1 separately, revealing a regulatory sequence of Notch1/Akt/Foxo1 ( P <0.05). In comparison to the NS group, NP mice administered with kisspeptin234 exhibited increased fetal absorption rates ( P <0.001) and decreased expression of IGFBP1, Notch1, Akt, and Foxo1 ( P <0.05). Conversely, RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates ( P <0.001) and increased expression levels of the aforementioned molecules ( P <0.05)., Conclusion: It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade. A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization, which in turn might contribute to the development or progression of RSA., Competing Interests: 利益冲突　永生化人子宫内膜基质细胞（hESC）为厦门大学医学与生命科学学院王海滨教授馈赠。除此之外，所有作者均声明不存在利益冲突。, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Epilepsy is a prevalent chronic neurological disorder characterized by recurrent seizures and brain dysfunction. Existing antiepileptic drugs (AEDs) mainly act on neurons and provide symptomatic control of seizures, but they do not modify the progression of epilepsy and may cause serious adverse effects. Increasing evidence suggests that reactive astrogliosis is critical in the pathophysiology of epilepsy. However, the function of reactive astrocytes in epilepsy has not been thoroughly explored. To provide a new perspective on the role of reactive astrocytes in epileptogenesis, we identified human astrocyte-specific genes and found 131 of these genes significantly differentially expressed in human temporal lobe epilepsy (TLE) datasets. Multiple astrocytic functions, such as cell adhesion, cell morphogenesis, actin filament-based process, apoptotic cell clearance and response to oxidative stress, were found to be promoted. Moreover, multiple altered astrocyte-specific genes were enriched in phagocytosis, perisynaptic astrocyte processes (PAPs), plasticity, and synaptic functions. Nine hub genes (ERBB2, GFAP, NOTCH2, ITGAV, ABCA1, AQP4, LRP1, GJA1, and YAP1) were identified by protein-protein interaction (PPI) network analysis. The correlation between the expression of these hub genes and seizure frequency, as well as epilepsy-related factors, including inflammatory mediators, complement factors, glutamate excitotoxicity and astrocyte reactivity, were analyzed. Additionally, upstream transcription factors of the hub genes were predicted. Finally, astrogliosis and the expression of the hub genes were validated in an epileptic rat model. Our findings reveal the various changes in astrocyte function associated with epilepsy and provide candidate astrocyte-specific genes that could be potential antiepileptogenic targets., 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.)

Systemic therapy is typically the primary treatment choice for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. Some patients may achieve partial response (PR) or complete response (CR) with systemic treatment, leading to the possibility of their primary tumor becoming resectable. This study aimed to investigate whether these patients could achieve longer survival through surgical resection of their primary tumor. We retrospectively collected data from 150 HCC patients with extrahepatic metastases treated at 15 different centers from January 1st, 2015, to November 30th, 2022. We evaluated their overall survival (OS) and progress-free survival (PFS) and analyzed risk factors impacting both OS and PFS were analyzed. Patients who received surgical treatment had longer OS compared to those who did not (median OS 16.5 months vs. 11.3 months). However, there was no significant difference in progression-free survival between the two groups. Portal vein invasion (P = 0.025) was identified as a risk factor for poor prognosis in patients, while effective first-line treatment (P = 0.039) and surgical treatment (P = 0.005) were protective factors. No factors showed statistical significance in the analysis of PFS. Effective first-line treatment (P = 0.027) and surgical treatment (P = 0.006) were both independent protective factors for prolonging patient prognosis, while portal vein invasion was an independent risk factor (P = 0.044). HCC patients with extrahepatic metastases who achieve PR/CR with conversion therapy may experience longer OS through surgical treatment. This study is the first to analyze the clinical outcomes of patients receiving surgical treatment for HCC with extrahepatic metastases., (© 2024. The Author(s).)

Ovarian cancer is the second most common cause of gynecologic cancer death. Chemoresistance and metastasis remain major challenges for current treatment. Previously, HAPSTR1 was shown to be a target gene of a paclitaxel resistance-associated miRNA. However, the biological function and underlying molecular mechanisms of HAPSTR1 in ovarian cancer progression remain unclear. Herein, we aimed to measure HAPSTR1 expression in ovarian cancer specimens and examine its correlations with clinical features and key functional interactions with other genes and proteins. An immunohistochemistry assay showed that HAPSTR1 was overexpressed in ovarian cancer tissues and was significantly associated with the FIGO stage and clinical outcome. HAPSTR1 overexpression promoted proliferation, invasion and migration in cellular and mouse models, whereas inhibition induced the opposite effects. In addition, HAPSTR1 stimulated the EMT pathway and affected the expression of autophagy biomarkers. Mechanistically, we demonstrated that HAPSTR1 is bound to LRPPRC and PSMD14 via immunoprecipitation. HAPSTR1 suppressed LRPPRC ubiquitination and recruited PSMD14 to interact with LRPPRC. Moreover, LRPPRC knockdown reversed HAPSTR1-mediated improvement in cellular proliferation, invasion, and migration. Our study is the first detailed and comprehensive analysis of HAPSTR1 in cancer progression and offers an experimental basis for the clinical treatment of ovarian carcinoma.

Background: Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported., Results: Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159&#95;164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR., Conclusions: Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases., (© 2024. The Author(s).)

Objective: To explore the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Spastic paraplegia type 5A (SPG5A)., Methods: A pedigree suspected for Hereditary spastic paraplegia (HSP) at Henan Children's Hospital on August 15 2022 was selected as the study subject. Clinical data of the pedigree was collected. Peripheral blood samples were collected from members of the pedigree. Following extraction of genomic DNA, trio-WGS was carried out, and candidate variant was verified by Sanger sequencing., Results: The child, a 1-year-old boy, had presented with microcephaly, hairy face and dorsal side of distal extremities and trunk, intellectual and motor development delay, increased muscle tone of lower limbs, hyperreflexes of bilateral knee tendons, and positive pathological signs. His parents and sister both had normal phenotypes. Trio-WGS revealed that the child has harbored a homozygous c.1250G>A (p.Arg417His) variant of the CYP7B1 gene, for which his mother was heterozygous, the father and sister were of the wild type. The variant was determined to have originated from maternal uniparental disomy (UPD). The result of Sanger sequencing was in keeping with the that of trio-WGS. SPG5A due to maternal UPD of chromosome 8 was unreported previously., Conclusion: The child was diagnosed with SPG5A, a complex type of HSP, for which the homozygous c.1250G>A variant of the CYP7B1 gene derived from maternal UPD may be accountable.

Objective: This study aimed to assess the knowledge, attitudes and practices (KAP) among Chinese reproductive-age women toward uterine adenomyosis., Methods: This web-based cross-sectional study was conducted between April 2023 and September 2023 at the Second Hospital of Hebei Medical University. A self-designed questionnaire was developed to collect demographic information of reproductive-age women, and assess their KAP toward uterine adenomyosis., Results: A total of 520 valid questionnaires were collected. Among the participants, 127 (24.42%) were diagnosed with uterine adenomyosis, and 120 (23.08%) were accompanied by uterine fibroids. The mean knowledge, attitudes and practices scores were 3.54 ± 3.72 (possible range:0-10), 20.96 ± 3.19 (possible range:5-25) and 24.01 ± 4.95 (possible range:7-35), respectively. The structural equation model demonstrated that knowledge had direct effects on attitudes and practices, as indicated by a path coefficient of 0.714 ( p  < 0.001) and 1.510 ( p  < 0.001), respectively. Moreover, attitudes had direct effects on practices, with a path coefficient of 0.226 ( p  = 0.001)., Conclusion: The findings revealed that reproductive-age women have insufficient knowledge, negative attitudes, and poor practices toward the uterine adenomyosis. Comprehensive training programs are needed to improve reproductive-age women practices in this area., 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 Ren, Li, Zhang, Li, Yuan, Li, Shan, Shi and Jiang.)

Background: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice., Methods: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline., Results: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory., Conclusions: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.

Objective: To explore the clinical features and genetic variants in three children suspected for β-ketothiolase deficiency (BKTD)., Methods: Clinical manifestations, laboratory examination and genetic testing of three children suspected for BKTD at Henan Children's Hospital between January 2018 and October 2022 were collected, and their clinical and genetic variants were retrospectively analyzed., Results: The children were all males with a age from 7 to 11 months. Their clinical manifestations have included poor spirit, shortness of breath, vomiting, convulsions after traumatic stress and/or infection. All of them had severe metabolic acidosis, elevated ketone bodies in blood and urine, hypoglycemia, with increased isoprenyl-carnitine and 3-hydroxyisovalyl-carnitine in the blood, and 2-methyl-3-hydroxybutyrate and methylprotaroyl glycine in the urine. All of them were found to harbor compound heterozygous variants of the ACAT1 gene, including c.1183G>T and a large fragment deletion (11q22.3-11q23.1) in child 1, c.121-3C>G and c.826+5&#95;826+9delGTGTT in child 2, and c.928G>C and c.1142T>C in child 3. The variants harbored by children 2 and 3 were known to be pathogenic or likely pathogenic. The heterozygous c.1183G>T variant in child 1 was unreported previously and rated as a variant of unknown significance (PM2&#95;Supporting+PP3+PP4) based on guidelines from the American College of Medical Genetics and Genomics. The large segment deletion in 11q22.3-11q23.1 has not been included in the DGV Database and was rated as a pathogenic copy number variation., Conclusion: The variants of the ACAT1 gene probably underlay the pathogenesis of BKTD in these three children.

The prognostic role of the Age-Adjusted Charlson Comorbidity Index (ACCI) in hilar cholangiocarcinoma patients undergoing laparoscopic resection is unclear. To evaluate ACCI's effect on overall survival (OS) and recurrence-free survival (RFS), we gathered data from 136 patients who underwent laparoscopic resection for hilar cholangiocarcinoma at Zhengzhou University People's Hospital between 1 June 2018 and 1 June 2022. ACCI scores were categorized into high ACCI (ACCI > 4.0) and low ACCI (ACCI ≤ 4.0) groups. We examined ACCI's association with OS and RFS using Cox regression analyses and developed an ACCI-based nomogram for survival prediction. Our analysis revealed that higher ACCI scores (ACCI > 4.0) (HR = 2.14, 95%CI: 1.37-3.34) were identified as an independent risk factor significantly affecting both OS and RFS in postoperative patients with hilar cholangiocarcinoma ( p  < 0.05). TNM stage III-IV (HR = 7.42, 95%CI: 3.11-17.68), not undergoing R0 resection (HR = 1.58, 95%CI: 1.01-2.46), hemorrhage quantity > 350 mL (HR = 1.92, 95%CI: 1.24-2.97), and not receiving chemotherapy (HR = 1.89, 95%CI: 1.21-2.95) were also independent risk factors for OS. The ACCI-based nomogram accurately predicted the 1-, 2-, and 3-year OS rates, with Area Under the Curve (AUC) values of 0.818, 0.844, and 0.924, respectively. Calibration curves confirmed the nomogram's accuracy, and decision curve analysis highlighted its superior predictive performance. These findings suggest that a higher ACCI is associated with a worse prognosis in patients undergoing laparoscopic resection for hilar cholangiocarcinoma. The ACCI-based nomogram could aid clinicians in making accurate predictions about patient survival and facilitate individualized treatment planning.

Ethnopharmacological Relevance: Heng-Gu-Gu-Shang-Yu-He-Ji (Osteoking, OK) is a well-known formula for fracture therapy. In clinic, OK is effective in treating fractures while alleviating osteoporosis (OP) symptoms. However, active components of OK and the associated molecular mechanisms remain not fully elucidated., Aim of the Study: This study aims to systematically evaluate the anti-osteoporosis efficacy of OK and for the first time combine network pharmacology with high-throughput whole gene transcriptome sequencing to study its underlying mechanism., Materials and Methods: In this study, the osteoporosis model was established by the castration of both ovaries. The level of serum bone turnover factor was detected by enzyme-linked immunosorbent assay. Micro-CT and HE staining were used to observe the changes of bone histopathology, and nano-indentation technique was used to detect the biomechanical properties of rat bone. The main active Chemical components of OK were identified using UPLC-DAD. Efficacy verification and mechanism exploration were conducted by network pharmacology, molecular docking, whole gene transcriptomics and in vivo experiments., Results: In our study, OK significantly improved bone microarchitecture and bone biomechanical parameters in OVX rats, reduced osteoclast indexes such as C-telopeptide of type I collage (CTX-I) and increased Osteoprotegerin (OPG)/Receptor activator of NF-κB ligand (RANKL) levels. Mechanistically, PI3K/AKT pathway was a common pathway for genome enrichment analysis (KEGG) of both network pharmacology and RNA-seq studies. G protein-β-like protein (GβL), Ribosomal-protein S6 kinase homolog 2 (S6K2), and Phosphoinositide 3-kinase (PI3K) appeared differentially expression in the PI3K-AKT signaling pathway. These results were also confirmed by qRT-PCR and immunohistochemistry., Conclusions: OK may be used to treat osteoporosis, at least partly by activating PI3K/AKT/mTORC1 signaling pathway., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Analyze the relationship between changes in the proportion of X-chromosome deletions and clinical manifestations in children with Turner syndrome (TS)., Methods: X-chromosome number abnormalities in 8,635 children with growth retardation were identified using fluorescence in situ hybridization (FISH). Meanwhile, the relationship between the proportion of X-chromosome deletions and the clinical manifestations of TS, such as face and body phenotype, cardiovascular, renal, and other comorbidities in children with TS was analyzed., Results: A total of 389 children had X-chromosome number abnormalities, with an average age at diagnosis of 9.2 years. There was a significant increase in diagnoses around the ages of 3 and 7 years and highest number of diagnoses at 10 years of age. 130 with XO (complete loss of an X-chromosome), 205 with XO/XX, 8 with XO/XXX, 23 with XO/XX/XXX, 19 with XO/XY, and 4 with XO/XY/XYY. Body and facial phenotypes increased with higher mosaicism proportions, with a relatively high correlation shown with Pearson correlation analysis ( r = 0.26, p = 1.7e-06). The incidence of congenital heart malformations was 25.56%, mainly involving a bicuspid aortic valve, and were more common in patients who had complete loss of an X-chromosome. However, this relationship was not present for renal disease ( p = 0.26), central nervous system, thyroid, or liver disease., Conclusion: The mosaicism (XO/XX) is the most common karyotype of TS in screened cases. The phenotypes in children with TS may increase with the proportion of X-chromosome deletions, but the renal disease and comorbidities did not show the same characteristics., 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 Wang, Liu, Wang, Wang, Zhang, Allegaert, Mei, Zhang, Luo, Fang, Li, Chen and Wei.)

Objective: To explore the clinical characteristics and genetic variants of two children with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD)., Methods: Two children with HMGCLD diagnosed at Henan Provincial Children's Hospital respectively in December 2019 and June 2022 were selected as the study subjects. Clinical data and results of laboratory testing were analyzed retrospectively., Results: Both children had manifested with repeated convulsions, severe hypoglycemia, metabolic acidosis and liver dysfunction. Blood amino acids and acylcarnitine analysis showed increased 3-hydroxy-isovalyl carnitine (C5OH) and 3-hydroxy-isovalyl carnitine/capryloyl carnitine ratio (C5OH/C8), and urinary organic acid analysis showed increased 3-hydroxyl-3-methyl glutaric acid, 3-methyl glutaric acid, 3-methyl glutaconic acid, 3-hydroxyisoglycine and 3-methylprotarylglycine. Child 1 was found to harbor homozygous c.722C>T variants of the HMGCL gene, which was rated as uncertain significance (PM2&#95;Supporting+PP3). Child 2 was found to harbor homozygous c.121C>T variants of the HMGCL gene, which was rated as pathogenic variant (PVS1+PM2&#95;Supporting+PP4)., Conclusion: Acute episode of HMGCLD is usually characterized by metabolic disorders such as hypoglycemia and metabolic acidosis, and elevated organic acids in urine may facilitate the differential diagnosis, though definite diagnosis will rely on genetic testing.

Background: Mitochondrial diseases are heterogeneous in terms of clinical manifestations and genetic characteristics. The dynamin 1-like gene (DNM1L) encodes dynamin-related protein 1 (DRP1), a member of the GTPases dynamin superfamily responsible for mitochondrial and peroxisomal fission. DNM1L variants can lead to mitochondrial fission dysfunction., Case Presentation: Herein, we report a distinctive clinical phenotype associated with a novel variant of DNM1L and review the relevant literature. A 5-year-old girl presented with paroxysmal hemiplegia, astigmatism, and strabismus. Levocarnitine and coenzyme Q 10 supplement showed good efficacy. Based on the patient's clinical data, trio whole-exome sequencing (trio-WES) and mtDNA sequencing were performed to identify the potential causative genes, and Sanger sequencing was used to validate the specific variation in the proband and her family members. The results showed a novel de novo heterozygous nonsense variant in exon 20 of the DNM1L gene, c.2161C>T, p.Gln721Ter, which is predicted to be a pathogenic variant according to the ACMG guidelines. The proband has a previously undescribed clinical manifestation, namely hemiparesis, which may be an additional feature of the growing phenotypic spectrum of DNM1L-related diseases., Conclusion: Our findings elucidate a novel variant in DNM1L-related disease and reveal an expanding phenotypic spectrum associated with DNM1L variants. This report highlights the necessity of next generation sequencing for early diagnosis of patients, and that further clinical phenotypic and genotypic analysis may help to improve the understanding of DNM1L-related diseases., (© 2024. The Author(s).)

Background: There is growing evidence that an antioxidant diet is a protective factor against frailty. However, few studies have examined the effect of comprehensive dietary antioxidants on frailty symptoms. The aim of this study was to examine the relationships between the composite dietary antioxidant index (CDAI) and frailty and the underlying mechanisms involved., Methods: Based on the National Health and Nutrition Survey (NHANES) 2003-2018, this study included 11,277 older persons aged ≥60 years. In this study, frailty was defined as having a total score >0.21 on the 49-item frailty index. Six dietary antioxidants were selected for use in calculating the CDAI. A weighted multiple logistic regression model with subgroup analysis and restricted cubic splines (RCSs) were used to examine the association between the CDAI and frailty. To examine the role of oxidative stress, mediation analyses were also conducted., Results: The association between the CDAI score and frailty risk was significant according to the multivariate model. Compared with participants in tertile 1, participants in both tertile 2 and tertile 3 had lower odds of developing frailty symptoms (OR=0.86; 95% CI=0.75-0.97; P=0.02; and OR=0.81; 95% CI=0.70-0.93; P=0.003). According to the subgroup analyses, the differences in interactions were not statistically significant. There was also a potential nonlinear relationship between the CDAI score and frailty risk. The serum albumin concentration and uric acid concentration had significant mediating effects on the association between the CDAI score and frailty index, with 19.25% ( P =0.002) and 21.26% ( P < 0.001) of the total, respectively., Conclusion: Frailty is negatively associated with the CDAI score, which may be partially mediated by oxidative stress., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wu et al.)

Dengue virus (DENV) infection causes dengue fever, the most prevalent arthropod-transmitted viral disease worldwide. Viruses are acellular parasites and obligately rely on host cell machinery for reproduction. Previous studies have indicated metabolomic changes in endothelial cell models and sera of animal models and patients with dengue fever. To probe the immunometabolic mechanism of DENV infection, here, we report the metabolomic landscape of a human macrophage cell model of DENV infection and its antibody-dependent enhancement. DENV infection of THP-1-derived macrophages caused 202 metabolic variants, of which amino acids occupied 23.7%, fatty acids 21.78%, carbohydrates 10.4%, organic acids 13.37%, and carnitines 10.4%. These metabolomic changes indicated an overall anabolic signature, which was characterized by the global exhaustion of amino acids, increases of cellular fatty acids, carbohydrates and pentoses, but decreases of acylcarnitine. Significant activation of metabolic pathways of glycolysis, pentose phosphate, amino acid metabolism, and tricarboxylic acid cycle collectively support the overall anabolism to meet metabolic demands of DENV replication and immune activation by viral infection. Totally 88 of 202 metabolic variants were significantly changed by DENV infection, 36 of which met the statistical standard (P<0.05, VIP>1.5) of differentially expressed metabolites, which were the predominantly decreased variants of acylcarnitine and the increased variants of fatty acids and carbohydrates. Remarkably, 11 differentially expressed metabolites were significantly distinct between DENV only infection and antibody-dependent enhancement of viral infection. Our data suggested that the anabolic activation by DENV infection integrates the viral replication and anti-viral immune activation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Problem: Immune factors are crucial in the development of recurrent spontaneous abortion (RSA). This study aimed to investigate whether kisspeptin regulates immune cells at the maternal-fetal interface and whether G protein-coupled receptor 54 (GPR54) is involved in this process, through which it contributes to the pathogenesis of RSA., Method of Study: Normal pregnancy (NP) (CBA/J × BALB/c) and RSA (CBA/J × DBA/2) mouse models were established. NP mice received tail vein injections of PBS and KP234 (blocker of kisspeptin receptor), whereas RSA mice received PBS and KP10 (active fragment of kisspeptin). The changes in immune cells in mouse spleen and uterus were assessed using flow cytometry and immunofluorescence. The expression of critical cytokines was examined by flow cytometry, ELISA, Western blotting, and qPCR. Immunofluorescence was employed to detect the coexpression of FOXP3 and GPR54., Results: The findings revealed that the proportion of Treg cells, MDSCs, and M2 macrophages in RSA mice was lower than that in NP mice, but it increased following the tail vein injection of KP10. Conversely, the proportion of these cells was reduced in NP mice after the injection of KP234. However, the trend of γδT cell proportion change is contrary to these cells. Furthermore, FOXP3 and GPR54 were coexpressed in mouse spleen and uterus Treg cells as well as in the human decidua samples., Conclusion: Our results suggest that kisspeptin potentially participates in the pathogenesis of RSA by influencing immune cell subsets at the maternal-fetal interface, including Treg cells, MDSC cells, γδT cells, and M2 macrophages., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Infectious wounds are difficult to heal because of vascular damage and immune imbalance. The multi-functional hydrogel dressing can regulate vascular regeneration and immune microenvironment through continuous supply of bioactive ingredients to the wound site, which can effectively accelerate the healing speed of infected wounds. In this work, a multifunctional dual-network hydrogel (QCMOD) with good injectability, stability, self-healing and adhesion was designed by combining methacrylic anhydride-modified quaternized chitosan (QCM) with oxidized dextran (OD) via Schiff base reaction and photo-crosslinked polymerization. Subsequently, MgO/Icariin composite nanoparticles with icariin coating were prepared and loaded in QCMOD hydrogel to establish nanohybrid dual-network chitosan-based hydrogels (QCMOD@MI), which possessed a controlled release of Mg 2+ and icariin as well as the ability of guiding physiological behavior in wound healing progress. In vitro results showed the nanohybrid hydrogel reduced bacterial infection and possessed multiple physiological functions including promoting cell migration, angiogenesis and reducing secretion of inflammatory factors. In vivo, the nanohybrid hydrogel showed excellent pro-healing abilities for infected full-thickness wounds by reducing bacterial infections and improving the microenvironment of ischemia and inflammation. This study provides a new paradigm for the design of multifunctional bioactive hydrogels and the obtained hydrogel is expected to become a new type of functional dressing., 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 Ltd. All rights reserved.)

Myocardial infarction (MI), an acute cardiovascular disease characterized by coronary artery blockage, inadequate blood supply, and subsequent ischemic necrosis of the myocardium, is one of the leading causes of death. The cellular, physiological, and pathological responses following MI are complex, involving multiple intertwined pathological mechanisms. Hypoxia-inducible factor-1 (HIF-1), a crucial regulator of hypoxia, plays a significant role in of the development of MI by modulating the behavior of various cells such as cardiomyocytes, endothelial cells, macrophages, and fibroblasts under hypoxic conditions. HIF-1 regulates various post-MI adaptive reactions to acute ischemia and hypoxia through various mechanisms. These mechanisms include angiogenesis, energy metabolism, oxidative stress, inflammatory response, and ventricular remodeling. With its crucial role in MI, HIF-1 is expected to significantly influence the treatment of MI. However, the drugs available for the treatment of MI targeting HIF-1 are currently limited, and most contain natural compounds. The development of precision-targeted drugs modulating HIF-1 has therapeutic potential for advancing MI treatment research and development. This study aimed to summarize the regulatory role of HIF-1 in the pathological responses of various cells following MI, the diverse mechanisms of action of HIF-1 in MI, and the potential drugs targeting HIF-1 for treating MI, thus providing the theoretical foundations for potential clinical therapeutic targets., 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.)

Aims: Assessing the global burden and health inequalities of Hypertension Heart Disease (HHD) during the period from 1990 to 2019., Methods: Secondary analysis of the Global Burden of Disease (GBD) study in 2019, focusing on the burden of diseases, injuries, and risk factors worldwide. Disability-Adjusted Life Years (DALYs) data related to HHD are extracted from the 2019 GBD. Inequality Slope Index (SII) and Concentration Index are calculated to assess health inequalities across regions and countries., Results: The total DALYs for HHD reached 21.51 million, demonstrating a substantial increase of 54.25% compared to the figures recorded in 1990, while the age-standardized DALY rates per 100,000 population for HHD in 2019 showed a notable decline to 268.19 (95% UI 204.57, 298.07), reflecting a significant decrease of 26.4% compared to the rates observed in 1990. The DALYs rate of hypertensive heart disease increases with age. Countries with moderate SDI accounted for 38.72% of the global burden of HHD in terms of DALYs. The highest age-standardized DALY rates (per 100,000) are predominantly concentrated in underdeveloped areas. In 1990 and 2019, the SII (per 100,000 population) for DALYs were - 121.6398 (95% CI -187.3729 to -55.90684) and - 1.592634 (95% CI -53.11027 to 49.925) respectively. The significant decline suggests a reduction in the inequality of age-standardized burden of HHD between high-income and low-income countries during this period., Conclusion: The unequal prevalence of HHD across different populations can hinder the achievement of the "health for all" objective. Persistent disparities in HHD have been observed globally over the past thirty years. It is crucial to prioritize efforts towards reducing avoidable health inequalities associated with hypertension-related heart disease, particularly in low-income and middle-income countries., (© 2024. The Author(s).)

Transition metal phosphides (TMPs) have been considered as potential electrocatalysts with adjustable valence states, metal characteristics, and phase diversity. However, it is necessary but remains a major challenge to obtain efficient and durable TMPs catalysts, which can realize efficiently for not only all-pH hydrogen evolution reaction (HER), but also oxygen evolution reaction (OER). Hence, cerium dioxide incorporated nickel cobalt phosphide growth on nickel foam (CeO 2 /NiCoP) is fabricated by hydrothermal and phosphating reaction. CeO 2 /NiCoP shows excellent activity for all-pH HER (overpotentials of 48, 58 and 72 mV in alkaline, neutral and acidic solution at the current density of 10 mA cm -2 ), and has a small OER overpotential (231 mV @ 10 mA cm -2 ). Moreover, the voltage of overall water splitting in alkaline solution and simulated seawater electrolyte is only 1.46 and 1.41 V (10 mA cm -2 ), respectively, coupled with outstanding operational stability and corrosion resistance. Further mechanism research shows that CeO 2 /NiCoP possesses rich heterointerfaces, which serves more exposed active sites and possesses a promising superhydrophilic and superaerophobic surface. Density functional theory calculations manifest that CeO 2 /NiCoP has appropriate energy for intermediates of reactions. This work provides a deep insight into the CeO 2 /NiCoP catalyst for high-performance water/seawater electrolysis., 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 Inc. All rights reserved.)

Background: Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease characterized by global development delay/intellectual disability, delayed language development, feeding difficulties, and distinctive facial dysmorphism. It is caused by pathogenic variants in YY1., Methods: The current report describes a female patient with motor delay and a facial dysmorphism phenotype. We identified pathogenic mutations in the patient by whole-exome sequencing and confirmed them by Sanger sequencing., Results: A novel heterozygous frameshift mutation NM&#95;003403.5:c.458&#95;476del (p. V153fs*97) in the YY1 gene was detected in the proband. Finally, we provide a case-based review of the clinical features associated with Gabriele-de Vries syndrome. A total of 28 patients with genetic abnormalities and clinical phenotypes have been reported in the literature thus far., Conclusions: The mutation site is reported for the first time, and its discovery would expand the mutation spectrum of the YY1 gene. The main clinical manifestations of Gabriele-de Vries syndrome are developmental delay/intellectual disability, craniofacial dysplasia, intrauterine growth delay, low birth weight, feeding difficulties, and rare congenital malformations. Genetic tests are crucial techniques for its diagnosis because of its nonspecific clinical manifestations., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Metal-organic frameworks (MOFs) that are the wonder material of the 21st century consist of metal ions/clusters coordinated to organic ligands to form one- or more-dimensional porous structures with unprecedented chemical and structural tunability, exceptional thermal stability, ultrahigh porosity, and a large surface area, making them an ideal candidate for numerous potential applications. In this work, the recent progress in the design and synthetic approaches of MOFs and explore their potential applications in the fields of gas storage and separation, catalysis, magnetism, drug delivery, chemical/biosensing, supercapacitors, rechargeable batteries and self-powered wearable sensors based on piezoelectric and triboelectric nanogenerators are summarized. Lastly, this work identifies present challenges and outlines future opportunities in this field, which can provide valuable references., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Global Challenges published by Wiley‐VCH GmbH.)

Ultrasonic flowmeter is one of the most widely used devices in flow measurement. Traditional bulk piezoelectric ceramic transducers restrict their application to small pipe diameters. In this paper, we propose an ultrasonic gas flowmeter based on a PZT piezoelectric micromachined ultrasonic transducer (PMUT) array. Two PMUT arrays with a resonant frequency of 125 kHz are used as the sensitive elements of the ultrasonic gas flowmeter to realize alternate transmission and reception of ultrasonic signals. The sensor contains 5 × 5 circular elements with a size of 3.7 × 3.7 mm 2 . An FPGA with a resolution of ns is used to process the received signal, and a flow system with overlapping acoustic paths and flow paths is designed. Compared with traditional measurement methods, the sensitivity is greatly improved. The flow system achieves high-precision measurement of gas flow in a 20 mm pipe diameter. The flow measurement range is 0.5-7 m/s and the relative error of correction is within 4%.

The threat of global climate change on wheat production may be underestimated by the limited capacity of many crop models to predict grain quality and protein composition. This study aimed to integrate a wheat quality module of protein components into the CROPSIM-CERES-Wheat model to investigate the impact of climate change on wheat grain yield and protein quality in the North China Region (NCR) using five Global Climate Models (GCMs) from CMIP6 under three shared socioeconomic pathways. The CERES-Wheat model with a quality module was developed and calibrated and validated using data from several sites in the NCR. The results of the calibration and validation showed that the modified CERES-Wheat model can accurately predict grain yield, protein content and its components in field experiments. Compared with the baseline period (1981-2010), the annual mean temperature and annual cumulative precipitation increased in the NCR in the 2030's, 2050's and 2080's. The radiation was higher under the SSP126 and SSP585 scenarios, and lower under the SSP370 scenario compared to the baseline period. The anthesis and maturity date occurred earlier under the three future scenarios. The average grain yield increased by 13.3-30.9 % under three future scenarios. However, the regional average grain protein content of winter wheat in the future decreased by 2.0 %- 3.5 %. The reduction in wheat grain protein at the regional was less pronounced under SSP370 than that under SSP126 and SSP585. The structural protein content of winter wheat decreased under future climate conditions compared with the baseline period, but the storage protein content showed the opposite tendency. The model provided a useful tool to study the effects of future climate on grain quality and protein composition. These findings are important for developing agricultural practices and strategies to mitigate the potential impacts of climate change on wheat production and wheat quality in the future., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hui Ju reports financial support was provided by Ministry of Science and Technology of the People's Republic of China. Di Zhang reports financial support was provided by Yangling Vocational and Technical College. Dongxiao Li reports financial support was provided by Ministry of Science and Technology of the People's Republic of China., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder. Research conducted on patients with OSA using electroencephalography (EEG) has revealed a noticeable shift in the overnight polysomnography (PSG) power spectrum. To better quantify the effects of OSA on brain function and to identify the most reliable predictors of pathological cortical activation, this study quantified the PSG power and its association with the degree of hypoxia in OSA patients., Patients and Methods: This retrospective study recruited 93 patients with OSA. OSA patients were divided into three groups based on their apnea-hypopnea index (AHI) scores. The clinical characteristics and sleep macrostructure of these patients were examined, followed by an analysis of PSG signals. Power spectral density (PSD) in five frequency bands was analyzed during nonrapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, and wakefulness. Finally, correlation analysis was conducted to assess the relationships among PSD, PSG parameters, and serum levels of S100β and uric acid., Results: Obstructive sleep apnea occurred during both the NREM and REM sleep phases. Except for a decrease in the duration of N2 sleep and an increase in the microarousal index, there were no significant differences in sleep architecture based on disease severity. Compared to the mild OSA group, the theta and alpha band PSD in the frontal and occipital regions during NREM sleep and wakefulness were significantly decreased in the moderate and severe OSA groups. Correlation analysis revealed that theta PSD in N1 and N3 stages were negatively correlated the AHI, oxygen desaturation index, SaO2<90% and microarousal index., Conclusion: These findings imply that patients with more severe OSA exhibited considerable NREM hypoxia and abnormal brain activity in the frontal and occipital regions. Therefore, sleep EEG oscillation may be a useful neurophysiological indicator for assessing brain function and disease severity in patients with OSA., Competing Interests: The authors report no conflicts of interest for this work., (© 2023 Zhang et al.)

One of the fundamental hurdles in infrared spectroscopy is the failure of molecular identification when their infrared vibrational fingerprints overlap. Refractive index (RI) is another intrinsic property of molecules associated with electronic polarizability, but with limited contribution to molecular identification in mixed environments currently. Here, we investigate the coupling mode of localized surface plasmon and surface phonon polaritons for vibrational de-overlapping. The coupling mode is sensitive to the molecular refractive index, attributed to the RI-induced vibrational variations of surface phonon polaritons (SPhP) within the Reststrahlen band, referred to as RI-dependent SPhP vibrations. The RI-dependent SPhP vibrations are linked to molecular RI features. According to the deep-learning-augmented demonstration of bond-breaking-bond-making dynamic profiling in biological reaction, we substantiate that the RI-dependent SPhP vibrations effectively disentangle overlapping vibrational modes, achieving a 92% identification accuracy even for the strongly overlapping vibrational modes in the reaction. Our findings offer insights into the realm of light-matter interaction and provide a valuable toolkit for biomedicine applications., (© 2023. The Author(s).)

Background: At present, the relationship between sleep and inflammatory factors is not clear. The aim of this study was to investigate the relationship between specific inflammatory factors and sleep in MDD patients., Methods: We measured and compared clinical features and 10 peripheral blood inflammatory factors in 40 MDD patients with sleep disorders, 80 MDD patients without sleep disorders, and 80 healthy controls. Correlation analysis and multiple linear regression analysis were used to explore the relationship between sleep and inflammatory factors., Result: The levels of IL-1β, IL-2, IL-6, IL-8, IL-10, CRP, TNF-α, CXCL-1, CXCL-2, and IFN-γ were different among the three groups(all p<0.05).Poor sleep quality was significantly negatively correlated with IL-2 and IL-8 (all p<0.01), and significantly positively correlated with IL-6, IL-10, CRP, TNF-α, CXCL-1, CXCL-2 and IFN-γ (all p<0.01). IL-8 could significantly negatively predict the deterioration of sleep quality (p<0.001), and TNF-a and IFN-γ could significantly positively predict the deterioration of sleep quality (all p<0.05)., Limitations: The self-rating scale was used in this study., Conclusions: Inflammatory factors are disrupted in patients with sleep disorders. The lower the level of IL-8 in peripheral blood of MDD patients, the higher the TNF-a and IFN-γ, and the worse the quality of sleep., Competing Interests: Declaration of Competing Interest The author declares that there is no potential conflict of interest of employment, consultancies, etc. among all the authors of this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The relationships of Klotho levels with cognition and dementia are poorly understood. This study aimed to investigate the association between Klotho levels and cognitive function and to determine causality between Klotho and dementia using Mendelian randomization (MR). Based on data from the National Health and Nutrition Survey (NHANES) 2011-2014, this study consisted of 1875 older adults aged 60-79 years. Cognitive function was assessed by the digit symbol substitution test (DSST). We performed weighted multivariable-adjusted linear regression to assess the association between Klotho concentrations and cognitive function. Then, 2-sample MR was conducted to assess the causal relationship between Klotho and dementia. The inverse variance weighted (IVW) method was used as the primary analysis. We observed a positive association between serum Klotho concentrations and the results of the Digit Symbol Substitution test (DSST) (T2: β 2.16, 95% CI: 0.30-4.01, P = 0.03, T3: β 2.48, 95% CI: 0.38-4.57, P = 0.02) after adjusting for the covariates. Moreover, there was also a potential nonlinear relationship between Klotho and DSST. The IVW method showed that genetically predicted high Klotho levels were not significantly associate with any type of dementia, including Alzheimer's disease (OR = 1.03, 95% CI: 0.96-1.10, P = 0.46), vascular dementia (OR = 1.04, 95% CI: 0.87-1.25, P = 0.66), frontotemporal dementia (OR = 0.73, 95% CI: 0.47-1.14, P = 0.16), or dementia with Lewy bodies (OR = 1.03, 95% CI: 0.87-1.23, P = 0.73). In the cross-sectional observational study, Klotho and cognitive function were significantly correlated; however, findings from MR studies did not indicate a causal relationship between Klotho and dementia., (© 2023. The Author(s).)

Background: The gut microbiota has emerged as an intriguing and potentially influential factor in regulating bone health. However, the causal effect of the gut microbiota on bone mineral density (BMD) appears to differ throughout various life stages., Methods: We conducted a Mendelian randomization (MR) analysis to investigate the potential causal relationship between gut microbiota and BMD in five distinct age groups: 0-15, 15-30, 30-45, 45-60, and 60 years and older. The analysis employed three different methods, namely MR-Egger, weighted median, and Inverse-variance weighting, to ensure the robustness of our findings, a series of sensitivity analyses were also conducted, such as horizontal pleiotropy tests, heterogeneity tests, and leave-one-out sensitivity tests., Results: In the age group of 0-15 years, Eubacterium&#95;fissicatena &#95;group and Eubacterium&#95;hallii &#95;group were identified as risk factors for BMD. During the 15-30 age group, Phascolarctobacterium , Roseburia , and Ruminococcaceae &#95;UCG&#95;003 were found to be protective factors for BMD. In the 30-45 age group, Lachnospira genus demonstrated a protective effect on BMD, while Barnesiella and Lactococcus were identified as risk factors for BMD. Moving on to the 45-60 age group, Eubacterium&#95;ventriosum &#95;group, Lachnospiraceae &#95;UCG&#95;004, and Subdoligranulum were observed to be protective factors for BMD, while Eubacterium&#95;coprostanoligenes &#95;group, Fusicatenibacter , and Lactococcus were associated with an increased risk of BMD. In individuals aged 60 years and older, Fusicatenibacter and Ruminococcaceae &#95;UCG&#95;002 were also noted as risk factors for BMD. Conversely, Eubacterium&#95;ruminantium &#95;group, Ruminococcus&#95;gauvreauii &#95;group, Alistipes , and Coprococcus &#95;3 were found to be protective factors for BMD, whereas Barnesiella and Sellimonas were identified as risk factors for BMD., Conclusion: A robust causal relationship between gut microbiota and bone mineral density (BMD) exists throughout all stages of life, with Firmicutes phylum being the primary group associated with BMD across age groups. Gut microbiota linked with BMD primarily belong to the Firmicutes phylum across age groups. The diversity of gut microbiota phyla associated with BMD depicts relatively stable patterns during the ages of 0-45 years. However, for individuals aged 45 years and above, there is an observed increase in the number of gut microbiota species linked with BMD, and by the age of 60 years, a trend toward an increase in the Bacteroidetes phylum categories is proposed., 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 Wang, Zhang, Tang, Deng, Qin, Han, Wang, Sun, Li and Chen.)

Background: Surgery for acetabular fractures involving both columns is difficult and traumatic, making it necessary to explore a minimally invasive and accurate surgical method., Methods: This retrospective case-control study analyzed the clinical data of 34 patients and divided them into two groups: a control group (9 males and 8 females) and a research group (11 males and 6 females) with acetabular fractures involving the anterior and posterior columns. All patients were placed in the supine position via the pararectus approach. A three-dimensional (3D) guide was placed at the position where the posterior column screw was inserted in the second window, and a posterior column screw was placed percutaneously on the medial side of the iliac spine in the research group. The operation time, intraoperative blood loss, and fracture union time of the two groups were recorded. Pelvic radiographs and computed tomography (CT) scans were routinely performed before and after surgery to evaluate reduction and fixation. Residual gap and step displacement were measured using a standardized CT-based method after the surgery. Hip mobility was assessed according to the modified Merle, d'Aubigné, and Postel criteria., Results: All patients were followed up for 6-30 (16.941±6.571) months. The operation times of the two groups were 126 [interquartile range (IQR), 95-133] min (control group) and 110 (IQR, 85-124) min (research group), the intraoperative blood losses were 430 (IQR, 290-550) mL (control group) and 380 (IQR, 260-500) mL (research group). All patients achieved bone healing, with a union time of 15 (IQR, 12-17) weeks (control group) and 13 (IQR, 11.5-15) weeks (research group). According to the standardized CT-based method, the reduction after surgery was acceptable in 13 (control group) and 14 (research group) of these patients (defined as a gap <5 mm or a step-off <1 mm), and the anatomical reduction rates were 76.47% and 82.35%, respectively., Conclusions: The use of a single pararectus approach combined with 3D guide-assisted percutaneous anterograde posterior column screws can shorten the operation time and place effective posterior column screws precisely with minimal invasiveness. At the same time, the acetabular reduction and functional recovery are satisfactory, and there are fewer postoperative complications, which makes this procedure an ideal surgical option., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-548/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Surface-enhanced infrared absorption (SEIRA) has proven its ability to improve the detection performance of traditional infrared spectroscopy at unprecedented levels. However, the resonant frequency of the metamaterial absorber (MA) lacks tunability once the structure is fabricated, which poses a challenge for broadband fingerprint retrieval of molecules. Here, we propose a pixelated and electric tunable hybrid graphene MA with a broadband response for molecular fingerprint retrieval. Loss engineering is employed to optimize the sensing sensitivity of MA. The resonant frequency of MA is approximately linearly modulated with a change in the graphene Fermi level. This design allows a meta-pixel to match multiple characteristic absorption spectra, thereby establishing a one-to-many mapping relationship between spatial and spectral information. The one-to-many mapping relationship greatly reduces the number of meta-pixels. As a concept demonstration, we integrate 9 meta-pixels to achieve full spectral coverage from 1000 cm -1 to 2000 cm -1 . Based on the broadband spectral properties of the sensor, we demonstrate its potential for multi-fingerprint detection, quantitative detection, chemical identification, and compositional analysis. Our proposed hybrid graphene MA can be easily integrated with other on-chip devices, providing a potential platform for optical sensing, infrared spectroscopy, and photodetection.

Background: Nonalcoholic steatohepatitis (NASH) is an advanced form of chronic fatty liver disease, which is a driver of hepatocellular carcinoma. However, the roles of the C5aR1 in the NASH remain poorly understood. Here, we aimed to investigate the functions and mechanisms of the C5aR1 on hepatic inflammation and fibrosis in murine NASH model., Methods: Mice were fed a normal chow diet with corn oil (ND + Oil), a Western diet with corn oil (WD + Oil) or a Western diet with carbon tetrachloride (WD + CCl 4 ) for 12 weeks. The effects of the C5a-C5aR1 axis on the progression of NASH were analyzed and the underlying mechanisms were explored., Results: Complement factor C5a was elevated in NASH mice. C5 deficiency reduced hepatic lipid droplet accumulation in the NASH mice. The hepatic expression levels of TNFα, IL-1β and F4/80 were decreased in C5-deficient mice. C5 loss alleviated hepatic fibrosis and downregulated the expression levels of α-SMA and TGFβ1. C5aR1 deletion reduced inflammation and fibrosis in NASH mice. Transcriptional profiling of liver tissues and KEGG pathway analysis revealed that several pathways such as Toll-like receptor signaling, NFκB signaling, TNF signaling, and NOD-like receptor signaling pathway were enriched between C5aR1 deficiency and wild-type mice. Mechanistically, C5aR1 deletion decreased the expression of TLR4 and NLRP3, subsequently regulating macrophage polarization. Moreover, C5aR1 antagonist PMX-53 treatment mitigated the progression of NASH in mice., Conclusions: Blockade of the C5a-C5aR1 axis reduces hepatic steatosis, inflammation, and fibrosis in NASH mice. Our data suggest that C5aR1 may be a potential target for drug development and therapeutic intervention of NASH., (© 2023. The Author(s).)