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Statins therapy is efficacious in diminishing the risk of major cardiovascular events in diabetic patients. However, our research has uncovered a correlation between the prolonged administration of statins and an elevated risk of myocardial dysfunction in patients with type II diabetes mellitus (TIIDM). Here, we report the induction of sterol regulatory element-binding protein 1 (SREBP1) activation, associated lipid peroxidation, and the consequent diabetic myocardial dysfunction after statin treatment and explored the underlying mechanisms. In db/db mice, we observed that 40 weeks atorvastatin (5 and 10 mg/kg) and rosuvastatin (20 mg/kg) administration exacerbated diabetic myocardial dysfunction by echocardiography and cardiomyocyte contractility assay, increased myocardial inflammation and fibrosis as shown by CD68, IL-1β, Masson's staining and Collagen1A1 immunohistochemistry (IHC) staining, increased respiratory exchange ratio (RER) by metabolic cage system assessment, exacerbated mitochondrial structural pathological changes by transmission electron microscopy (TEM) examination, increased deposition of lipid and glycogen by TEM, Oil-red and periodic acid-schiff stain (PAS) staining, which were corresponded with augmented levels of myocardial SREBP1 protein and lipid peroxidation marked by 4-hydroxynonenal (4-HNE) staining. Comparable myocardial fibrosis was also observed in KK-ay and low-dose streptozotocin (STZ)-induced TIIDM mice. Elevated SREBP1 levels were observed in the heart tissues from diabetic patients, which was positively correlated with their myocardial dysfunction. To elucidate the role of statin induced SREBP1 in lipid peroxidation and lipid deposition and related mechanism, we cultured neonatal mouse primary cardiomyocytes (NMPCs) and treated them with atorvastatin (10 μM, 24 h), tracing with [U–13C]-glucose and evaluating for SREBP1 expression and localization. We found that statin treatment elevated de novo lipogenesis (DNL) and the levels of SREBP1 cleavage-activating protein (SCAP), reduced the interaction of SCAP with insulin-induced gene 1 (Insig1), and enhance SCAP/SREBP1 translocation to the Golgi, which facilitate SREBP1 cleavage leading to its nuclear trans-localization and activation in NMPCs. Ultimately, SREBP1 knockdown or l-carnitine mitigated long-term statins therapy induced lipid peroxidation and myocardial fibrosis in low-dose STZ treated SREBP1+/− mice and l-carnitine treated db/db mice. In conclusion, we demonstrated that statin therapy may augment DNL by activating SREBP1, resulting in myocardial lipid peroxidation and lipid deposition.

Information on vegetation dynamics is important for agricultural and ecological management. However, a systematic framework for the study of vegetation dynamics is still lacking. Therefore, this study developed the Vegetation Dynamic Change And Land Cover (VDCALC) framework to achieve a comprehensive analysis of vegetation dynamic change. The framework uses the Normalized Difference Vegetation Index (NDVI) data derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) and Global Inventory Modeling and Mapping Studies (GIMMS), along with land cover data as input. It combines several models, including the Theil-Sen median, Mann-Kendall test and coefficient of variation, which can qualitatively and quantitatively study the spatiotemporal dynamic change of vegetation, and Hurst exponent model, which was used to predict the future change. Meteorological and statistical data were used as auxiliary data in this framework to analyze the influencing factors of vegetation change. Results showed that the degradation area was mainly concentrated in the coastal areas of the peninsula, Rizhao, Weifang, Linyi and Zibo during the period from 2001 to 2015, accounting for 36.05%. Based on annual-scale data, the NDVI showed an overall improvement trend, with significant increases in spring and autumn. However, predictions indicated that the degraded area would account for 37.18% in the future. In addition, meteorological factors were found to influence vegetation growth differently depending on the season. This study demonstrated a complete and reliable framework for effectively reflecting regional vegetation changes. It is recommended for application in large-scale areas to guide agricultural and ecological management.

The eco-friendly synthesis of palladium nanoparticles (PdNPs) utilizing plant phytochemicals has demonstrated its efficacy as a nano-catalyst for azo dye degradation. However, the catalytic prowess of these nanoparticles has been predominantly explored on specific model compounds. Consequently, a fundamental inquiry arises: Can these nanoparticles uniformly catalyze a spectrum of diverse azo dyes, irrespective of structural intricacies, azo bond quantity, side-chain functional groups, molecular weight (Mw) fluctuations, water solubility gradients, ionic characteristics, and dye classification (reactive or acid)? To address this comprehensively, nine azo compounds, encompassing the aforementioned criteria, were systematically chosen for catalysis utilizing the synthesized PdNPs. The synthesized particles were spherical (∼10.5 nm in diameter) with highly crystalline surfaces (d-spacing of 0.194–0.224 nm) and have a uniform size distribution. Employing green chemistry principles and Eucommia ulmoides bark extract (EUBE), this synthesis exhibits exceptional catalytic efficiency across a varied array of azo dyes, achieving degradation rates of up to 99% within 1–5 minutes. This methodical exploration offers a holistic understanding of the catalytic capabilities of PdNPs, shedding light on their potential applicability across a diverse spectrum of azo compounds, thereby propelling advancements in the field.

Biological macromolecules, encompassing plant phytochemicals, biopolymers, and polysaccharides, are validated for simultaneous metal cation reduction and their stabilization for metal nanoparticles (NPs) through green synthesis. The application of these biosynthesized NPs in azo dye catalysis is established but limited to specific model compounds. The fundamental question emerges: Do these NPs uniformly catalyze across diverse azo dyes, disregarding structural complexity, azo bond count, side chain functional groups, molecular weight (Mw) variations, water solubility levels, ionic nature, and dye class (reactive or acid)? To comprehensively investigate, nine azo compounds meeting the aforementioned criteria were chosen for catalysis using synthesized silver NPs (AgNPs). This synthesis employs Eucommia ulmoides bark extract (EUBE) within green chemistry principles. The synthesized AgNPs, predominantly spherical and nano-sized (5–14 nm) with uniform distribution and a highly crystalline surface, are securely stabilized by a thin membrane of EUBE phytochemicals, exhibiting no agglomeration. It yields outstanding catalytic performance on a diverse group of azo dyes, achieving up to 100% degradation within 1–16 min. The reaction adheres to a pseudo-kinetic first-order mechanism. This systematic approach provides a comprehensive insight into the catalytic prowess of AgNPs, elucidating their potential across a diverse range of azo compounds, thereby advancing knowledge in the field.

Starting from the theoretical mechanism of the impact of financial agglomeration on regional green innovation efficiency, and using panel data from 30 provinces in China from 2009 to 2017, this study calculates a financial agglomeration index and green innovation efficiency applying principal component analysis and the slacks-based measure (SBM) of super-efficiency. The study then constructs static and dynamic spatial Durbin models using two different spatial weight matrices to empirically test the spatial spillover effect of financial agglomeration on regional green innovation efficiency. The results reveal a significant positive spatial correlation between China's inter-provincial green innovation efficiency and financial agglomeration. Both static and dynamic models demonstrate that financial agglomeration has a significant spatial spillover effect on the green innovation efficiency of adjacent provinces, but the static model overestimates the impact of spatial spillover. In addition, human capital level, technology market activity, and environmental regulation all have significant positive impacts on the green innovation efficiency of provinces and adjacent provinces.

Obesity is a foremost health issue that affects about 1.6 million people out of which 400 million worldwide. Epidemiological evidences prove obesity is the primary cause for various metabolic ailments e.g. diabetes. Poria cocos possess extensive biological actions, for instance, antioxidant, anti-inflammatory, antitumor, immunomodulatory actions. The primary limitation of all phytomedicine was their poor bioavailability hence in this investigation, we bio-fabricated the gold nanoparticles from Poria cocos aqueous extract and inspected their potency to treat obesity. Obese rat model were produced via fed the young female rats with high fat food for 8 weeks regimen. Further to confirm the potency of Poria cocos gold nanoparticles against obesity induced metabolic disorders we treated obese rats with low dose streptozotocin in the conclusion of the investigational time. The synthesis of Poria cocos gold-nanoparticles was evidenced via the UV-Spectroscopic study and characterized with SEM, TEM and EDAX studies. The anti-obesity actions of Poria cocos gold-nanoparticles were investigated by estimating the glucose profile, kidney markers, lipid profile, inflammatory cytokines, adipocyte markers, antioxidants in the Poria cocos gold nanoparticles treated obese rats. To confirm the Poria cocos gold nanoparticles role on inhibiting the obesity induced metabolic disorders we analyzed the histopathological changes in cardiac tissues. Our physical characterization confirms the synthesized Poria cocos gold nanoparticles assure the distinctions of influential nanoparticles to be utilized for the treatment. The results from biochemical and histopathological analysis confirms Poria cocos gold nanoparticles is a persuasive antidiabetic, anti-inflammatory, antioxidant, anti-obesity drug. Overall our results authentically confirm Poria cocos gold nanoparticles is a potent anti-obesity drug and it also protects from obesity induced metabolic disorders.

Objective: Functional deficits induced by nerve injuries can be restored by achieving effective reinnervation of the denervated targets and functional reorganization of the central nervous system after nerve reconstruction. In this study, we investigated the effect and extent of cortical functional reorganization related to the ability of transferred hypoglossal neurons to restore facial function in facial paralysis patients after a surgical bridge of neurorrhaphy ectopically between the ipsilateral hypoglossal nerve and injured facial nerve. Methods: We treated 23 patients (35.4 ± 10.3 years, 10 males) and followed them up for 2.9 ± 0.61 years. We used motor-task-related functional magnetic resonance imaging to map activation change at multiple time points before and after neurorrhaphy; 20 normal subjects were included as control. Results: All patients regained facial function to some extent after neurorrhaphy. Enhanced activation in motor-related cortices gradually returned to normal levels and was positively correlated with regained facial function. The related cortical functional areas included the left middle temporal gyrus, left inferior frontal gyrus, insula, bilateral motor cortex and the supplementary motor area extending to the paracingulate involved in intensive eye closing, as well as the left superior temporal gyrus, right putamen and the bilateral motor cortex involved in lip pursing. Intriguingly, significant correlations were found between the pre-surgery activation while intensive eye closing in bilateral motor cortex and recovery of facial nerve function induced by the neurorrhaphy treatment. Conclusion: This is the first study mapping activation change in motor cortices at multiple time points before and after repair of the facial nerve. The cortex functional reorganization found may suggest potential treatment targets in the central nervous system for adjuvant therapies such as repetitive transcranial magnetic stimulation to further improve functional recovery.

There is no previous study on the effect of pinocembrin on ovarian cancer to the best of our knowledge. Moreover, the effects of pinocembrin on the expression of GABAB1 and GABAB2 genes are not studied before. Therefore, this study aimed to investigate effects of pinocembrin on the growth of ovarian cancer cells and the expression of cadherin and GABAB receptor to explore whether pinocembrin was helpful in the treatment of epithelial ovarian cancer. SKOV3 cells were divided into six groups: Control (blank control), DDP (cisplatin as positive control; cells were incubated with 15 μg/ml DDP), 25 μM (cells were incubated with 25 μM pinocembrin), 50 μM (cells were incubated with 50 μM pinocembrin), 100 μM (cells were incubated with 100 μM pinocembrin), and 200 μM (cells were incubated with 200 μM pinocembrin). CCK8 assay, cell scratch assay and Annexin V-FITC/PI staining found that when pinocembrin concentration reached 100 μM and the treatment time reached 48 h, pinocembrin could inhibit the cell proliferation and migration and promote the cell apoptosis, and this effect was enhanced with the increase of pinocembrin concentration. Western blotting found that the protein expression of E-cadherin, N-cadherin, GABAB1 and GABAB2 was not significantly affected by pinocembrin. RT-PCR found that pinocembrin also had no significant influence on the E-cadherin mRNA level, but it could reduce the mRNA levels of N-cadherin, GABAB1 and GABAB2. In conclusion, pinocembrin inhibited the proliferation and migration and promoted the apoptosis of ovarian cancer cells through down-regulating the mRNA levels of N-cadherin and GABAB receptor.

This data article contains extended, complementary analysis related to the research articles entitled “Desmoglein 3, via an interaction with E-cadherin, is associated with activation of Src” (Tsang et al., 2010) [1] and figures related to the review article entitled “Desmoglein 3: a help or a hindrance in cancer progression?” (Brown et al., 2014) [2]. We show here that both Src and caveolin-1 (Cav-1) associate with Dsg3 in a non-ionic detergent soluble pool and that modulation of Dsg3 levels inversely alters the expression of Src in the Cav-1 complex. Furthermore, immunofluorescence analysis revealed a reduced colocalization of Cav-1/total Src in cells with overexpression of Dsg3 compared to control cells. In support, the sequence analysis has identified a region within the carboxyl-terminus of human Dsg3 for a likelihood of binding to the scaffolding domain of Cav-1, the known Src binding site in Cav-1, and this region is highly conserved across most of 18 species as well as within desmoglein family members. Based on these findings, we propose a working model that Dsg3 activates Src through competing with its inactive form for binding to Cav-1, thus leading to release of Src followed by its auto-activation. Keywords: Desmoglein, Src signaling, Caveolin, Sequence alignment

Cell death is a central process for organismal health. Pyroptosis, namely pyroptotic cell death, is recognized as a critical type that disrupts membrane and triggers pro-inflammatory cytokine secretion via gasdermins, providing a robust form of cytolysis. Meanwhile, along with the thorough research, a great deal of evidence has demonstrated the dual effects of pyroptosis in host defense and inflammatory diseases. More importantly, the recent identification of abundant gasdermin-like proteins in bacteria and fungi suggests an ancient origin of pyroptosis-based regulated cell death in the life evolution. In this review, we bring a general overview of pyroptosis pathways focusing on gasdermin structural biology, regulatory mechanisms, and recent progress in induction and inhibition strategies for disease treatment. We look forward to providing an insightful perspective for readers to comprehend the frame and challenges of the pyroptosis field, and to accelerating its clinical application.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Finger joint angle (FJA) estimation, as a dynamic and fine-grained decoding mode, can support intuitive and natural human–machine interactions. This study is pioneering work dedicated to achieving accurate and clinically friendly FJA estimation. In this context, a novel surface electromyography and force myography-based multimodal multistream multilevel fusion network (MMMFNet) is proposed. MMMFNet utilises gate-recurrent units (GRU) networks to capture spatial dependencies among features and adopts a multilevel fusion strategy to extract more comprehensive representations from information sources than a single-level fusion. A cross-stream interaction (CSI) block is added between the GRU networks to focus on important information in the prediction and optimise the learning process and representation capability by facilitating information interaction among branch networks. The experimental results suggest that the MMMFNet has higher estimation accuracy (RMSE: 6.225±0.276 vs. 6.953±0.282, R2: 0.879±0.019 vs 0.846±0.021), shorter training time (4.146±0.074 min vs. 16.536±0.430 min), and lower computational complexity (5.4×106 FLOPs vs 8.8×106 FLOPs) than state-of-the-art fusion methods. Moreover, MMMFNet, which quantifies feature importance using attention weights, is the first explainable multimodal model for hand movement intention decoding. In summary, compared with state-of-the-art methods, MMMFNet can not only estimate FJAs more accurately but is also more clinically friendly.

Summary: Hypervirulent Klebsiella pneumoniae (hvKp) is a significant causative agent of invasive hepatic abscess syndrome in Asia, presenting substantial clinical challenges due to its intricate pathogenesis. This study revealed the crucial role of the gut microbiota in fortifying the host’s defense against hvKp infection by enhancing interleukin-22 (IL-22), probably through regulating downstream antimicrobial peptides such as Reg3β. In antibiotic-treated mice, we observed that gut microbiota disruption impaired the transformation of tryptophan to indole, a key ligand for the aryl hydrocarbon receptor (AhR), consequently affecting the regulatory functions of IL-22. Our experimental findings revealed that administering rIL-22 or indole propionic acid notably diminished the translocation of hvKp from the intestine to the liver. This research not only underscores the pivotal role of the gut microbiome in modulating tryptophan metabolism and the IL-22 pathway but also highlights its critical function in preventing hvKp migration from the colon to the liver.

Mitochondria, traditionally recognized as cellular 'powerhouses' due to their pivotal role in energy production, have emerged as multifunctional organelles at the intersection of bioenergetics, metabolic signaling, and immunity. However, the understanding of their exact contributions to immunity and inflammation is still developing. This review first introduces the innovative concept of intracellular immunity, emphasizing how mitochondria serve as critical immune signaling hubs. They are instrumental in recognizing and responding to pathogen and danger signals, and in modulating immune responses. We also propose mitochondria as the leading immune organelles, drawing parallels with the broader immune system in their functions of antigen presentation, immune regulation, and immune response. Our comprehensive review explores mitochondrial immune signaling pathways, their therapeutic potential in managing inflammation and chronic diseases, and discusses cutting-edge methodologies for mitochondrial research. Targeting a broad readership of both experts in mitochondrial functions and newcomers to the field, this review sets forth new directions that could transform our understanding of intracellular immunity and the integrated immune functions of intracellular organelles.

Background: Gerberae Piloselloidis Herba (GPH) exhibits notable efficacy in alleviating allergic asthma. Previous studies in our research have identified a mixture of luteolin, arbutin, and marmesin as effective components of GPH in treating allergic asthma. However, the underlying mechanism remains unclear. This study aims to elucidate the molecular mechanism of these active components. Method: Using an ovalbumin (OVA)-induced allergic asthma mouse model, various treatment groups were administered, including GPH, the active component mixture (termed ''Mixture'') containing luteolin, arbutin, and marmesin, and a positive drug (dexamethasone, DEX). Relevant indices were assessed, including behavioral characteristics, inflammatory cell counts, cytokine levels, histopathological examination of lung tissue, apoptosis, and expression of key proteins such as Caspase-3, Bax, Bcl-2, PI3K, p-PI3K, Akt, and p-Akt. The effect of the Mixture on the PI3K/Akt signaling pathway was further verified using the PI3K inhibitor LY294002. Results: The Mixture significantly alleviated asthma symptoms, decreased IgE levels, cytokine levels (IL-4, IL-5, IL-13 and TNF-α), and the number of inflammatory cells in serum or bronchoalveolar lavage fluid (BALF), leading to the alleviation of lung pathological lesions. Additionally, the Mixture reduced the expression of Bax and Caspase-3 while increasing Bcl-2 expression, resulting in mitigated apoptosis in lung tissue. Furthermore, there appeared a decrease in the levels of PI3K and p-PI3K, as well as the ratio of p-Akt to Akt in the Mixture group, indicating the suppression of PI3K and Akt phosphorylation. Interestingly, the effects of the Mixture were comparable to those of GPH, LY294002, or the combination of LY294002 with the Mixture. Conclusion: The study confirms that the Mixture containing luteolin, arbutin, and marmesin indeed alleviates allergic asthma induced by OVA in mice by suppressing the PI3K/Akt signaling pathway. These findings highlight the potential of the GPH-derived Mixture as a novel therapeutic for the treatment of allergic asthma.

Anterior cruciate ligament (ACL) injury is a common knee sports injury, with proximal ACL tears accounting for most cases. Arthroscopic ACL preservation has shown great potential in repairing ACL anatomic and biological function, with less tissue damage and slightly higher failure rates. Although many techniques for repairing the ACL have been developed, there are still many problems with the existing technology, such as the cumbersome operation of the traditional hook and needle breakage of the Scorpion suture passer (Arthrex). Herein, to further improve operational convenience and reliability, we developed a continuous bundle suture technique for primary repair of proximal ACL tears with suture anchor fixation. This technique aims to achieve continuous suturing with no additional auxiliary suture for guiding suturing by using a passer as a pusher in the suture hook to push out the suture loaded in the tip of the hook after the hook passes through the ligament. This technique takes advantage of the economics of the suture hook and the convenience of the Scorpion suture passer, allowing for flexible application of the suture hook to conveniently achieve anteromedial and posterolateral bundle repair for patients with proximal ACL tears.

Semantic segmentation of high-resolution multispectral remote sensing image has been intensely studied. However, the shadow occlusions, or the similar color and textures, between the categories influence the segmentation accuracy. Concomitantly, the size of targets in the remote sensing images is diverse and the network cannot balance their segmentation. This paper introduces a network, Transformer-based Multi-modal Fusion Network (TMFNet), which fuses the multi-modal features and incorporates height features from the digital surface model (DSM) to supplement the extra different features between each category. Particularly, we introduce two parallel encoders to extract the features from different modalities, a Multi-Modal fusion model based on the Transformer (MMformer) to complete the multi-modal fusion, and a Border Region Attention based multi-level Fusion Module (BRAFM) to integrate the cross-level features and enhance the small target segmentation by utilizing the details around the border. The experiment results on the ISPRS Vaihingen and Potsdam benchmark datasets indicate that the proposed TMFNet outperforms the SOTA methods on the segmentation performance.

During outdoor work in April 2022, a 48-year-old man was stabbed by a tree branch and underwent intraocular foreign body extraction and repair of the scleral wound with sutures and amniotic membrane graft at a local hospital. Steroid therapy with prednisone was prescribed after a diagnosis of uveitis. Vitrectomy was performed in June 2023; a fungal culture was positive, and ITS sequencing identified the organism as Paradictyoarthrinium diffractum. Empiric antifungal therapy did not have an effect, and, because of deterioration of the condition, the left eye was enucleated in October 2023. P. diffractum is a mangrove host-specific saprophytic fungus that has not been reported in humans.

Recent studies have documented that post-traumatic stress disorder (PTSD) symptoms are robustly associated with depressive symptoms and may mediate the relationship between trauma exposure and depressive symptoms. However, no study has explored the differential mediating effects of four specific PTSD symptom clusters. This study made the first attempt to examine the mediating effects of different PTSD symptom clusters on the linkage between trauma exposure and depressive symptoms. We analyzed data from two large samples of Chinese middle school students (N = 693 and 957) who had experienced the 2013 Ya'an earthquake. Participants completed standardized measures of trauma exposure, PTSD symptoms, and depressive symptoms. The prevalence of probable PTSD was 3.4% and 3.6%, respectively, in the two samples. Mediation analyses revealed that negative alterations in cognitions and mood and alterations in arousal and reactivity were statistically significant mediators in the relationship between trauma exposure during the earthquake and depressive symptoms. The results are very consistent in both samples. The findings suggest that symptom-specific tailored management of these two specific PTSD symptom clusters might have the potential to change the trajectory of developing depressive symptoms among trauma-exposed populations.

Slight distortions can cause dramatic changes in the properties of crystalline perovskite materials and their derivatives. Due to the numerous types of distortions and unclarified distortion-structure relations, a quantitative distortion manipulation for the desired crystalline phase of perovskite materials suitable for various application remains challenging. Here, by establishing parameter sets to systematically describe the types, magnitudes and positional relations involved in distortions, we are able to interpret the structural regulations and manipulation strategies in 7 reported crystal systems. Through the construction of distortion-phase-property functional curves, we further propose a paradigm to quantify the structural distortion manipulation for desired perovskite phases. Using the example of perovskite-like tungsten oxides, we successfully quantify their volume shrinkage and symmetry increase during lithiation. This work verifies that the complicated research and development of perovskite materials can be simplified into a mathematical problem solving process, which will inspire researchers with different backgrounds to participate, especially mathematicians and computer scientists.

Distortion manipulation emerges as an efficient approach to obtain desired perovskite phases for various applications. In part I of this study, we propose a paradigm to quantify the structural distortion manipulation, which enables us to obtain desired perovskite phases by translating relevant materials research into a single mathematical question. As part II of this continuous study, we construct normalized structures by introducing all possible couplings of dominant distortions into a cubic supercell and then compare them with variously shaped primitive/conventional cells known in the database. The structure comparison demonstrates that distortions are the only cause for phase and property variations. This confirms that our proposed distortion parameters can be directly used to construct phases, providing theoretical support for the paradigm in Part I. Given the limited number of distortion types, we identify that the positional relations involved in distortion arrangements and couplings are the keys to describe numerous phases. Furtherly, a three-step workflow is proposed with core contents related to the positional relation, distortion hierarchy, and distortion-component-generation ordering in spatial dimension, respectively. The definition basis and value changes of distortion/model parameters in this workflow illustration provide guidelines about how to reveal the logic behind the perovskite phase evolution.

Background: Traumatic injuries to the lower extremities are frequently accompanied by extensive soft tissue loss, combined with vascular damage or exposure of bony tissues, making it difficult to reconstruct; consequently, patients are commonly at risk of amputation. Due to its superior anatomical and biochemical properties, the omental flap has been used to reconstruct soft tissue defects for decades. However, few studies have reported the omental flap's effectiveness in treating severe and complex lower extremity deformities. We attempted to use a laparoscopically harvested omental flap in conjunction with a second-stage skin graft to reduce infections during limb preservation, increase flap survival probability, and restore the aesthetic and functional integrity of the affected extremity. Methods: Seventeen patients with severe lower extremity wounds underwent omental flap transplantation and were followed up for 6 to 12 months to check for surgical complications, evaluate cosmetic results, and ensure proper limb function. Results: There were no complications, such as intestinal adhesion, intestinal volvulus, and peritonitis, with any of the omental grafts. The affected extremities were well-functioning and aesthetically pleasing. Conclusion: Laparoscopically harvested omental flap transplantation with skin grafting is an alternative reconstruction technique for severe lower extremity injuries with massive soft tissue loss and exposed bones and tendons.

To investigate the ability of sulfonated polyetheretherketone (SPEEK) to promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and compare the effects of different degrees of sulfonation (DS), SPEEK was made with two different DS. The L-SPEEK group had a lower DS, while the H-SPEEK group had a higher DS. The physicochemical properties of both species were evaluated by scanning electron microscopy (SEM), capitilize Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Then, proliferation and osteogenic differentiation between the two groups and with pure polyetheretherketone (PEEK) were compared after surface inoculation of bone marrow mesenchymal stem cells (BMSCs). Scanning electron microscopy (SEM) revealed that the surface of the PEEK substrates could be smooth or coarse, and the degree of roughness increased with increasing sulfonation. FTIR spectroscopy showed that both the L-SPEEK and H-SPEEK samples contained sulfonic acid. TGA and XRD revealed that the components in the two groups were the same, but the intensities were different. After BMSC inoculation, a CCK8 assay revealed that the cells proliferated more on the H-SPEEK surface and little on the L-SPEEK surface compared with the PEEK surface. Then, osteogenic differentiation was verified by immunofluorescence staining for OCN and Runx2, which indicated that H-SPEEK had the greatest effect on improving differentiation. The results of alizarin red staining (ARS) and alkaline phosphatase staining (APS) also revealed this trend. Sulfonation can change the microsurface of PEEK, which can improve both BMSC proliferation and osteogenic differentiation.

Triclosan is a potent antibacterial compound widely used in everyday products. Whether triclosan affects Leydig cell function in adult male rats remains unknown. In this study, 0, 50, 100, or 200 mg/kg/day triclosan was gavaged to Sprague-Dawley male rats from 56 to 63 days postpartum. Triclosan significantly reduced serum testosterone levels at ≥ 50 mg/kg/day via downregulating the expression of Leydig cell gene Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3 and regulatory transcription factor Nr3c2 at 100–200 mg/kg. Further analysis showed that triclosan markedly increased autophagy as shown by increasing LC3II and BECN1 and decreasing SQSTM1. The mRNA m6A modification analysis revealed that triclosan significantly downregulated Fto expression at 200 mg/kg while upregulating Ythdf1 expression at 100 and 200 mg/kg, leading to methylation of Becn1 mRNA as shown by MeRIP assay. Triclosan significantly inhibited testosterone output in rat R2C Leydig cells at ≥ 5 μM via downregulating Fto and upregulating Ythdf1. SiRNA Ythdf1 knockdown can reverse triclosan-mediated mitophagy in R2C cells, thereby reversing the reduction of testosterone output. In summary, triclosan caused Becn1 m6A methylation by downregulating Fto and upregulating Ythdf1, which accelerated Becn1 translation, thus leading to the occurrence of autophagy and the decrease of testosterone biosynthesis.

Objective: This study aims to provide an updated overview of the relationship between carbon monoxide poisoning (COP) and cardiovascular disease. Methods: A systematic literature search was conducted in PubMed, Embase, Cochrane, and Web of Science databases up to September 2023. The association between COP patients and cardiovascular adverse events was examined and summarized. The outcomes included arrhythmia, coronary heart disease, heart failure, myocardial infarction, major adverse cardiovascular events (MACE), carboxyhaemoglobin percent (COHB%), Pondus Hydrogenii (PH) electrocardiography (ECG) parameters. Results: Eight eligible articles, involving a total of 251,971 patients, were included for evidence synthesis. The analysis revealed a heightened incidence of MACE in patients with COP. Additionally, COP exhibited an impact on specific ECG parameters. The incidence of MACE after COP was found to be similar in Korean and Chinese populations, and there was no significant effect of gender or underlying diseases on MACE incidence following COP. The incidence of MACE after COP did not differ significantly in individuals aged 50 years and older. Conclusions: Considering the observed heterogeneity and potential biases in the selected studies, emergency physicians should be aware of the increased likelihood of cardiovascular events in patients diagnosed with COP.

Summary: The emergence of SARS-CoV-2 variants raises concerns about the efficacy of existing COVID-19 vaccines and therapeutics. Previously, we identified a conserved cryptic class 5 epitope of SARS-CoV-2 receptor binding domain (RBD) by two cross-neutralizing antibodies 7D6 and 6D6. Intriguingly, this site remains resistant to substantial mutations occurred in ever-changing SARS-CoV-2 subvariants. As compared to class 3 antibody S309, 6D6 maintains broad and consistent neutralizing activities against SARS-CoV-2 variants. Furthermore, 6D6 effectively protected hamster from the virulent Beta strain. Sequence alignment of approximately 6 million documented SARS-CoV-2 isolates revealed that 6D6 epitope maintains an exceptionally high conservation rate (99.92%). Structural analysis demonstrated that all 33 mutations accumulated in XBB.1.5 since the original strain do not perturb the binding 6D6 to RBD, in line with the sequence analysis throughout the antigenicity evolution of SARS-CoV-2. These findings suggest the potential of this epitope serving as a critical determinant for vaccines and therapeutic design.

In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia and in human coronary artery disease by analyzing metabolic profiles. We found that HHcy worsening is most sensitive to other metabolic disorders. To identify metabolic genes and metabolites responsible for the worsening metabolic crosstalk, we examined mRNA levels of 324 metabolic genes in Hcy, glucose-related and lipid metabolic systems. We examined Hcy-metabolites (Hcy, SAH and SAM) by LS-ESI-MS/MS in 6 organs (heart, liver, brain, lung, spleen, and kidney) from C57BL/6J mice. Through linear regression analysis of Hcy-metabolites and metabolic gene mRNA levels, we discovered that SAH-responsive genes were responsible for most metabolic changes and all metabolic crosstalk mediated by Serine, Taurine, and G3P. SAH-responsive genes worsen glucose metabolism and cause upper glycolysis activation and lower glycolysis suppression, indicative of the accumulation of glucose/glycogen and G3P, Serine synthesis inhibition, and ATP depletion. Insufficient Serine due to negative correlation of PHGDH with SAH concentration may inhibit the folate cycle and transsulfurarion pathway and consequential reduced antioxidant power, including glutathione, taurine, NADPH, and NAD+. Additionally, we identified SAH-activated pathological TG loop as the consequence of increased fatty acid (FA) uptake, FA β-oxidation and Ac-CoA production along with lysosomal damage. We concluded that HHcy is most responsive to other metabolic changes in concomitant metabolic disorders and mediates worsening metabolic crosstalk mainly via SAH-responsive genes, that organ-specific Hcy metabolism determines organ-specific worsening metabolic reprogramming, and that SAH, acetyl-CoA, Serine and Taurine are critical metabolites mediating worsening metabolic crosstalk, redox disturbance, hypomethylation and hyperacetylation linking worsening metabolic reprogramming in metabolic syndrome.

Accurate estimation of evapotranspiration (ET) at high spatial resolution is crucial for drought monitoring and water resources management, but currently available remote sensing ET products generally have coarse spatial resolution (≥1000 m). To estimate ET at a high spatial resolution, Landsat images, Global Land Surface Satellite (GLASS), Moderate Resolution Imaging Spectroradiometer (MODIS), and meteorological forcing data were integrated, and the surface energy balance (SEBS) model was employed to calculate the 16-day average ET at 30 m resolution for China’s Tarim River Basin, spanning from 2009 to 2018. The results indicated that the average 16-day ET estimates correlated well with ground observations for land and water surfaces (root mean square error (RMSE) for land = 0.92 mm day−1, RMSE for water = 1.63 mm day−1, mean bias for land = 0.3 mm day−1, mean bias for water = 0.52 mm day−1). Cross validation with GLASS, ETMonitor, and Penman-Monteith-Leuning (PML_V2) ET datasets revealed an overall increasing trend for all four products (PML_V2 = 6.277 mm year−1, GLASS = 2.185 mm year−1, ETMonitor = 3.258 mm year−1, SEBS = 1.441 mm year−1), demonstrating good spatial consistency. The consistent increasing pixels were primarily distributed in the northern, southwestern, and southeastern mountainous regions, accounting for 22.8%, while 0.29% of the consistent decreasing pixels were mainly concentrated in the central desert and mountain-front oasis areas. Inconsistent pixels accounted for 76.9%, with 2.34% of the inconsistent decreasing pixels exhibiting a scattered distribution, while 37.28% of the inconsistent increasing pixels were mainly found in the central desert and some oasis areas. Furthermore, SEBS ET trend analysis indicated that the oasis area experienced more pronounced changes than the mountainous and desert areas during the 2009–2018 period. The SEBS ET estimated in this study can provide high-precision data support and a reference for future research on the water resources management.

This study investigated the impact of different temperatures and durations on the structural and emulsifying properties of copra meal protein. Additionally, the stability of copra meal protein Pickering emulsions was assessed through rheological and interfacial characteristics. Findings revealed a positive correlation between emulsification properties and heating temperature and duration. Thermal aggregates, facilitated by hydrogen bonds, hydrophobic interactions, and disulfide bonds, significantly enhanced surface hydrophobicity. Heat-treated copra meal protein-based Pickering emulsions demonstrate enhanced adsorption at the oil-water interface and resistance to diffusion. The three-phase contact angle increases from 57.7° to 79.8° following heating at 95 °C for 30 min. The addition of NaCl and heating treatment did not affect emulsion particle size or interface adsorption ability. But it improved the rheological properties to varying degrees. These results offer valuable insights for optimizing the physicochemical and functional attributes of copra meal protein in the food industry.

To characterize the oscillating flow and heat transfer characteristics of the cooling gallery inside a steel piston, a visual experimental platform was designed and constructed. Based on experimental results, simulation models of the cooling gallery under calibration conditions were established, and the oscillating flow and heat transfer characteristics of different oil injection strategies were studied. The results show that adjusting the nozzle diameter has a more significant impact on the fluid charge ratio (FCR) of the cooling gallery compared to the injection pressure. During the reciprocating motion of the steel piston inside the cylinder, the gallery has the largest heat transfer coefficient (HTC) on the Top wall at the top dead center (TDC) and the largest value on the Bottom wall at the bottom dead center (BDC). The average HTC of the Top wall is always the largest, followed by the Bottom wall, the In wall, and the Out wall being the smallest. Compared to the original design, the average HTC of the Top, Bottom, Out, and In walls can be increased by a maximum of 4.39 %, 3.96 %, 8.01 %, and 11.80 %, respectively.

Passive icephobic coatings attract increasing attention due to their harmless strategy for preventing undesirable ice accumulation. Slippery liquid-infused surfaces display extremely low ice adhesion (τice) but are argued for their poor stabilities and longevities due to inevitable liquid consumption. Herein we reported a class of lubricated polysiloxane coatings that can maintain low τice (∼2.2 kPa) for a long time (>800 icing/deicing cycle). The coatings have slippery lubricated surfaces and switchable porous matrices loading a large amount of liquid in isolated porevoids. Such droplet-embedded structure allows the surfaces to continuously maintain highly swelling states in a self-adaptive manner, i.e., only in the conditions icing or oil consumption occur dose oil is released, and thus show excellent long-term icephobicity. Besides, these materials exhibit good mechanical properties, antifatigue, and substrate adhesion. Because the coatings can be prepared via facile and green method from cheap starting materials, we foresee their broad application prospect in many fields.

As the complexity of autonomous vehicles (AVs) continues to increase and artificial intelligence algorithms are becoming increasingly ubiquitous, a novel safety concern known as the safety of the intended functionality (SOTIF) has emerged, presenting significant challenges to the widespread deployment of AVs. SOTIF focuses on issues arising from the functional insufficiencies of the AVs’ intended functionality or its implementation, apart from conventional safety considerations. From the systems engineering standpoint, this study offers a comprehensive exploration of the SOTIF landscape by reviewing academic research, practical activities, challenges, and perspectives across the development, verification, validation, and operation phases. Academic research encompasses system-level SOTIF studies and algorithm-related SOTIF issues and solutions. Moreover, it encapsulates practical SOTIF activities undertaken by corporations, government entities, and academic institutions spanning international and Chinese contexts, focusing on the overarching methodologies and practices in different phases. Finally, the paper presents future challenges and outlook pertaining to the development, verification, validation, and operation phases, motivating stakeholders to address the remaining obstacles and challenges.

Purpose: To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment. Methods: This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay. Results: Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation. Conclusions: Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Uncoordinated mutant number-45 myosin chaperone A (UNC-45A), a protein highly conserved throughout evolution, is ubiquitously expressed in somatic cells. It is correlated with tumorigenesis, proliferation, metastasis, and invasion of multiple malignant tumors. The current understanding of the role of UNC-45A in tumor progression is mainly related to the regulation of non-muscle myosin II (NM-II). However, many studies have suggested that the mechanisms by which UNC-45A is involved in tumor progression are far greater than those of NM-II regulation. UNC-45A can also promote tumor cell proliferation by regulating checkpoint kinase 1 (ChK1) phosphorylation or the transcriptional activity of nuclear receptors, and induces chemoresistance to paclitaxel in tumor cells by destabilizing microtubule activity. In this review, we discuss the recent advances illuminating the role of UNC-45A in tumor progression. We also put forward therapeutic strategies targeting UNC-45A, in the hope of paving the way the development of UNC-45A-targeted therapies for patients with malignant tumors.

The growth of the biodiesel industry has resulted in significant quantity of crude glycerol. It is necessary to explore the synthesis of high-value-added products from crude glycerol. In this study, the enzymatic synthesis of monoglycerides under solvent-free conditions, employing crude glycerol as the primary feedstock, had been investigated. The analysis showed that the highest yield of monoglycerides was obtained after 12 h, and Novozym 435 showed the highest monoglyceride yield of 18.41 % among the three lipases tested, followed by Lipozyme TL IM and Lipozyme RM IM. Monoglycerides were synthesized from biodiesel-derived crude glycerol using Novozym 435 as the catalyst under solvent-free conditions at different parameters, which were catalyst concentration, substrate molar ratio, and temperature. The yield of monoglycerides was examined in single-factor experiments. Response surface methodology (RSM) was subsequently employed to optimize the synthesis conditions based on the single-factor experimental results. The optimal conditions were at an enzyme concentration of 12.7 wt% and a molar ratio of crude glycerol:oil of 5.7:1 at a reaction temperature of 65.2 °C. The experimental yield of monoglycerides under the optimal conditions was 28.93 %, which is close to the value predicted from the RSM model (29.02 %).

Summary: Embryos, originating from fertilized eggs, undergo continuous cell division and differentiation, accompanied by dramatic changes in transcription, translation, and metabolism. Chromatin regulators, including transcription factors (TFs), play indispensable roles in regulating these processes. Recently, the trophoblast regulator TFAP2C was identified as crucial in initiating early cell fate decisions. However, Tfap2c transcripts persist in both the inner cell mass and trophectoderm of blastocysts, prompting inquiry into Tfap2c’s function in post-lineage establishment. In this study, we delineate the dynamics of TFAP2C during the mouse peri-implantation stage and elucidate its collaboration with the key lineage regulators CDX2 and NANOG. Importantly, we propose that de novo formation of H3K9me3 in the extraembryonic ectoderm during implantation antagonizes TFAP2C binding to crucial developmental genes, thereby maintaining its lineage identity. Together, these results highlight the plasticity of the chromatin environment in designating the genomic binding of highly adaptable lineage-specific TFs and regulating embryonic cell fates.

The screening and identification of drug metabolites in biological matrices is challenging, and ultra-high performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) has become a powerful technological tool for drug metabolites analysis due to its high sensitivity. However, the spectral information contained in existing chemical standards and databases is very limited, and the UHPLC-Q-Exactive Orbitrap MS technique alone cannot satisfy the identification of complex and diverse metabolites. Therefore, there is an urgent need for a new strategy to achieve comprehensive drug metabolic profile. Based on this, we have innovatively constructed a “recursive tree” analysis strategy and bridged it with network pharmacology for elucidating the pharmacological mechanisms of drugs. In this paper, we investigated the overall metabolic profile of formononetin as an example and utilized the primary branching metabolites of formononetin as effective ingredients for the study of the anti-NAFLD mechanism. The results showed that a total of 131 metabolites (prototype drug included) were detected and identified. Among them, 106 metabolites were found in rats and 31 metabolites were found in liver microsomes. Glucose conjugation, demethylation, sulfation, glucuronidation, and their complex reactions were the major processes of formononetin biotransformation. Network pharmacology results screened 104 potential targets and 20 major signaling pathways. Their mechanisms may be additive and/or synergistic effects. In addition, the therapeutic effects of formononetin against NAFLD were investigated based on palmitic acid / oleic acid-induced HepG2 cells. In summary, the recursive tree analysis strategy provides a convenient method for the identification of metabolites, and its seamless integration with network pharmacology lays the foundation for studying the pharmacological activities of natural products.

The residue remaining after oil extraction from grape seed contain abundant procyanidins. An ultrasonic-assisted enzyme method was performed to achieve a high extraction efficiency of procyanidins when the optimal extraction conditions were 8 U/g of cellulase, ultrasound power of 200 W, ultrasonic temperature of 50 ℃, and ultrasonic reaction time of 40 min. The effects of free procyanidins on both radical scavenging activity and thermal stability at 40, 60, and 80 ℃ of the procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were discussed. The presence of procyanidins at concentrations ranging from 0.02 to 0.10 mg/mL was observed to be effective at inhibiting lipid oxidation by 15.15 % to 69.70 % in a linoleic acid model system during reaction for 168 h, as measured using the ferric thiocyanate method. The procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were characterized by measuring the mean particle size and encapsulation efficiency. Moreover, the holographic plots showed that the effect–response points of procyanidins combined with α-tocopherol in liposomes were lower than the addition line and 95 % confidence interval limits. At the same time, there were significant differences between the theoretical IC50add value and the experimental IC50mix value. The interaction index (γ) of all combinations was observed to be less than 1. These results indicated that there was a synergistic antioxidant effect between procyanidins combined with α-tocopherol, which will show promising prospects in practical applications. In addition, particle size differentiation and morphology agglomeration were observed at different time points of antioxidant activity determination (0, 48, 96 h).

The ceRNA network, consisting of both noncoding RNA and protein-coding RNA, governs the occurrence, progression, metastasis, and infiltration of lung adenocarcinoma. Signatures comprising multiple genes can effectively determine survival stratification and prognosis of patients with lung adenocarcinoma. To explore the mechanisms of lung adenocarcinoma progression and identify potential biological targets, we carried out systematic bioinformatics analyses of the genetic profiles of lung adenocarcinoma, such as weighted gene co-expression network analysis (WGCNA), differential expression (DE) assessment, univariate and multivariate Cox proportional hazard regression models, ceRNA modulatory networks generated using the ENCORI and miRcode databases, nomogram models, ROC curve assessment, and Kaplan-Meier survival curve analysis. The ceRNA network encompassed 37 nodes, comprising 12 mRNAs, 22 lncRNAs, and three miRNAs. Simultaneously, we performed integration analysis using the 12 genes from the ceRNA network. Our findings revealed that the signature established by these 12 genes serves as an adverse element in lung adenocarcinoma, contributing to unfavorable patient prognosis. To ensure the credibility of our results, we used in vitro experiments for further verification. In conclusion, our study delved into the potential mechanisms underlying lung adenocarcinoma via the ceRNA regulatory network, specifically focusing on the PIF1 and has-miR-125a-5p axis. Additionally, a signature comprising 12 genes was identified as a biomarker related to the prognosis of lung adenocarcinoma.

Summary: Fuel cells (FCs) have attracted widespread attention as a highly efficient, clean, and renewable energy conversion technology. Proton exchange membrane (PEM), as one of the core components of FCs, plays a crucial role, and a comprehensive summary of its development is essential for promoting rapid progress in the field of sustainable energy. This article provides a comprehensive review of the development status and research trends of PEMs over the past twenty-eight years, based on statistical analysis and data mining techniques. Price, sustainability, stability, and compatibility issues are the main challenges faced by current PEMs used in FCs research. The current research focuses mainly on the characterization, performance optimization, enhancement mechanisms, and applications of PEMs in FCs. This review provides a systematic summary of PEM materials, serving as a valuable reference for the development, application, and promotion of new PEM materials in FCs.

Hydrolysis/alcoholysis/ammonolysis are considered as viable routes for efficient degradation and recycling of polyethylene terephthalate waste plastic. The possible hydrolysis/alcoholysis/ammonolysis pathways for the degradation of ethylene terephthalate dimer were investigated by the density functional theory (DFT) method M06/cc-pVDZ. The geometric structure optimization and frequency calculation of various intermediates, transition states and products involved in the reaction were carried out to obtain thermodynamic and kinetic parameter values. The results show that the reaction energy barrier of the cracking process of ethylene terephthalate dimer can be reduced under the conditions of hydrolysis/alcoholysis/ammonolysis, which makes the reaction easier. Additionally, at 298 K and 1 atm, the total rate constants of hydrolysis/alcoholysis/ammonolysis are 1.51 × 10-43 cm3 molecular-1s−1, 1.86 × 10-41 cm3 molecular-1s−1, and 2.82 × 10-40 cm3 molecular-1s−1, respectively. The hydrolysis products of ethylene terephthalate dimer are mainly terephthalic acid and ethylene glycol; the alcoholysis products of ethylene terephthalate dimer are dimethyl terephthalate and ethylene glycol; and ammonolysis products mainly include terephthalamide and ethylene glycol. Furthermore, this study shows that the Gibbs free energy change of hydrolysis/alcoholysis/ammonolysis is negatively correlated with temperature and an increase in temperature enhance the spontaneity of the reaction.

Accurate genetic diagnosis is necessary for guiding the treatment of spinal muscular atrophy (SMA). An updated consensus for the diagnosis and management of SMA was published in 2018. However, clinicians should remain alert to some pitfalls of genetic testing that can occur when following a routine diagnosis. In this study, we report the diagnosis of three unrelated individuals who were initially misdiagnosed as carrying a homozygous deletion of SMN1 exon 7. MLPA (P060 and P021) and qPCR were used to detect the copy number of SMN. SMN1 variants were identified by SMN1 clone and next-generation sequencing (NGS). Transcription of SMN1 variants was detected using qRT-PCR and ex vivo splicing analysis. Among the three individuals, one was identified as a patient with SMA carrying a heterozygous deletion and a pathogenic variant (c.835-17_835-14delCTTT) of SMN1, one was a healthy carrier only carrying a heterozygous deletion of SMN1 exon 7, and the third was a patient with nemaline myopathy 2 carrying a heterozygous deletion of SMN1 exon 7. The misdiagnosis of these individuals was attributed to the presence of the c.835-17_835-14delCTTT or c.835-17C > G variants in SMN1 intron 6, which affect the amplification of SMN1 exon 7 during MLPA-P060 and qPCR testing. However, MLPA-P021 and NGS analyses were unaffected by these variants. These results support that additional detection methods should be employed in cases where the SMN1 copy number is ambiguous to minimize the misdiagnosis of SMA.

Objectives: Methylmalonic acidemia (MMA) is a rare inborn genetic disorder that is characterized by increased levels of methylmalonic acid in blood plasma and urine. Isolated methylmalonic acidemia is one of the most common types of MMA and is caused by mutations in the gene encoding methyl-malonyl coenzyme A mutase (MMUT). In this study, we investigated the possible mechanisms underlying the symptoms of isolated MMA in a patient by molecular analysis. Methods: PCR amplification and Sanger sequencing analysis was performed to identify variants in the MMUT gene in the proband and his family. Furthermore, minigene constructs were generated to validate the splicing defects in the MMUT gene variant identified in the proband. Results: The 3-year-old patient was admitted to the hospital with symptoms of MMA, including fever, convulsions, and vomiting. He showed metabolic acidosis, high levels of methylmalonic acid in blood and urine, and normal blood homocysteine levels. Genetic analysis demonstrated that the patient was a compound heterozygous carrier of two variants in the MMUT gene: a missense c.278G > A variant that has already been reported in a patient with the severe mut⁰ phenotype; and a novel splice site variant c.2125-2A > G. RT-PCR analysis showed that, while the novel variant clearly alters splicing, a minor amount of a full-length transcript is generated, suggesting that a wild-type protein may be produced although at a lower quantitative level. The patient's condition improved after treatment with vitamin B12. Serious complications were not reported during follow-up at age 5. Conclusions: We identified a novel splice site variant that partially disrupts normal splicing of the MMUT pre-mRNA. Production of a reduced amount of full-length transcript is responsible for the mild clinical phenotype observed in this patient. Functional studies have proven useful in exploring the genotype‐phenotype association and in providing guidance for the genetic diagnosis of MMA.

Both phloretin and phlorizin (phloretin 2′-O-glucoside) extracted from the peel of apples are attributed to particular flavonoid dihydrochalcones with multiple pharmacological activities. However, metabolite structural characterization of these two components, which may accumulate to exert their pharmacological effects, remains insufficient. The present study aimed to comparatively clarify the metabolic pathways of phloretin and phlorizin after oral administration individually to Sprague-Dawley (SD) rats. Therefore, a rapid, integrate and systematic analytical strategy based on characteristic fragment ion fishing was proposed for the screening and identification of metabolites coming from phloretin and phlorizin using UHPLC-Q-Exactive Orbitrap mass spectrometry in parallel reaction monitoring mode. As a result, a total of 50 phloretin metabolites and 52 phlorizin metabolites were individually identified from different biological samples including rat plasma, urine, and faeces. Moreover, glucuronidation, sulfation, carbonylation and hydrolyzation were revealed to be the main metabolic pathways of phlorizin, while decarbonylation, glucuronidation and sulfation were regarded as the predominant biotransformation pathways as for phloretin. This is the first systematic study on comparison of metabolic profiles of phlorizin and phloretin in disease states, which was helpful to declare the complicated structure activity relationships between phlorizin and phloretin and shed light to their action mechanism.

Irinotecan is an anticancer topoisomerase I inhibitor that acts as a prodrug of the active metabolite, SN-38. Unfortunately, the limited utility of irinotecan is attributed to its pH-dependent stability, short half-life and dose-limiting toxicity. To address this problem, a novel trivalent PEGylated prodrug (PEG-[Irinotecan]3) has been synthesized and its full-profile pharmacokinetics, antitumor activity and toxicity compared with those of irinotecan. The results show that after intravenous administration to rats, PEG-[Irinotecan]3 undergoes stepwise loss of irinotecan to form PEG-[Irinotecan]3‒x (x = 1,2) and PEG-[linker] during which time the released irinotecan undergoes conversion to SN-38. As compared with conventional irinotecan, PEG-[Irinotecan]3 displays extended release of irinotecan and efficient formation of SN-38 with significantly improved AUC and half-life. In a colorectal cancer-bearing model in nude mice, the tumor concentrations of irinotecan and SN-38 produced by PEG-[Irinotecan]3 were respectively 86.2 and 2293 times higher at 48 h than produced by irinotecan. In summary, PEG-[Irinotecan]3 displays superior pharmacokinetic characteristics and antitumor activity with lower toxicity than irinotecan. This supports the view that PEG-[Irinotecan]3 is a superior anticancer drug to irinotecan and it has entered the phase II trial stage.

In the paper, the (La0.2Dy0.2Nd0.2Sm0.2Eu0.2)2GdTaO7 oxide was prepared employing sol–gel and solid-reaction method. Its crystal-structure, microstructure, element-distribution, mechanical and thermophysical properties are investigated. The analytical conclusions reveal that this high-entropy oxide shows single pyrochlore structure, dense microstructure, and even element distribution. Owing to the strong phonon scattering originated from high-entropy effect and numerous oxygen vacancies, it has low thermal conductivity and ranges from 1.41 to 1.27 W/m. K. Its coefficient of thermal expansion is less than those of rare-earth cerium oxides and greater than that of 7YSZ. The Young's modulus of this high-entropy oxide is in the same order with 7YSZ, its Vickers hardness and fracture-toughness are lower than those of 7YSZ. This high-entropy oxide is also of excellent lattice-stability up to 1200 °C.

Al2O3–Cr2O3 refractories have excellent slag corrosion resistance and can adapt to the oxidation/reduction atmosphere in the smelting reduction ironmaking furnace. Improving the corrosion resistance of chrome corundum refractories is of great significance for extending the life length of industrial kilns and decreasing carbon emissions. In this work, the influences of ZrO2 content on the phase evolution, microstructure, physicochemical properties, mechanical properties and slag corrosion resistance of the ZrO2 reinforced Al2O3–Cr2O3 composite refractories were investigated. The results show that the ZrO2 reinforced Al2O3–Cr2O3 composites are primarily composed of (Al, Cr)2O3 solid solution and m-ZrO2. The compressive strength, flexural strength and hardness of the composite refractories can be improved by adding 2.5 wt% ZrO2. However, adding more ZrO2 will reduce its mechanical properties. This is due to ZrO2 excessive content will augement the porosity of the composite refractories, and the phase transformation of ZrO2 will also lead to the formation of microcracks during the cooling process. It is worth noting that higher ZrO2 content improves the thermal shock resistance of the composites, which is primarily put down to the microcrack toughening mechanism of ZrO2. The corrosion tests show that the thicknesses of the corrosion and infiltration layers of composite refractories are significantly decreased accompanied by ZrO2 content increase. This is because the formation of high melting point CaZr4O9 reduces the CaO content and slag alkalinity, and inhibits the dissolution of Al2O3 into the slag to a certain extent. Therefore, the slag corrosion/penetration resistance of the of the composites are obviously improved with the increase of ZrO2 addition.