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Ethnopharmacological Relevance: Lizhong decoction (LZD) is a frequently utilized traditional Chinese remedy for diarrhea. It is unknown how effective it is as an antiviral against PEDV infection., Aim of the Study: In vitro and in vivo PEDV infection models were used to evaluate the anti-PEDV potential of LZD extract., Materials and Methods: LC-MS was used for qualitative analysis of LZD. The antiviral effect of LZD against PEDV using flow cytometry (FC), Quantitative real-time polymerase chain reaction (QPCR), immunofluorescence assay (IFA) analysis in Vero and IPEC-J2 cells. Additionally, we measured the survival rate, clinical symptoms, body weights, fecal scores, temperature, histological analysis, and viral load in a model of newborn piglets infected with PEDV in order to assess the antiviral impact of LZD in vivo., Results: In total, 648 compounds were identified, including 144 Alkaloids, 128 Terpenoids, etc. LZD effectively suppressed PEDV replication in vitro. According to time of addition experiments, LZD mostly inhibited PEDV during the viral life cycle's replication stages. During PEDV infection, LZD can Significantly decrease the apoptotic rate of IPEC-J2 cells and Vero cells. In comparison to the model group, LZD was able to decrease the viral titers in the infected piglets' intestinal and visceral tissues, ameliorate their intestinal pathology, cause a significant increase in body weight growth and increase the piglet survival rate., Conclusion: Our findings indicate that the aqueous solution derived from LZD suppressed PEDV replication both in vitro and in vivo, indicating its potential as a candidate for pharmaceutical development., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

It has been reported that the self-assembly pattern of light levitating droplet clusters above the hot gas-liquid interface is dependent on the quantity of droplets. However, the already-reported theoretical explanation of the quantity-dependent self-assembly pattern cannot work well when the quantity of the light levitating droplet exceeds 15. Herein, we propose a new theoretical perspective to understand the self-assembly of a light levitating droplet cluster by referring to the classical densest packing problem of identical rigid circles in a larger circle with the introduction of the minimum total potential energy principle. Amazingly, the theoretical results obtained by this new approach agree well with experimental results, even though the quantity of the light levitating droplet is up to 142. This study deepens our understanding of the quantity-dependent self-assembly pattern of the light levitating droplet clusters and provides significant inspiration for other analogous self-assembly phenomena.

Neuropathic pain results from damage to nerves or the brain, and is characterized by symptoms such as allodynia, spontaneous pain, and hyperalgesia. The causes of this type of pain are intricate, which can make it difficult to treat. Sodium aescinate (SA), a natural extract from horse chestnut tree seeds, has been shown to act as a neuroprotector by inhibiting microglia activation. This study aims to explore the therapeutic potential of SA for neuropathic pain and the molecular mechanisms regulated by SA treatment. Through in vivo animal models and experiments, we found that SA treatment significantly reduced mechanical allodynia and heat hyperalgesia in neuropathic pain models. Additionally, SA inhibited O-GlcNAc-transferase (OGT)-induced O-GlcNAcylation (O-GlcNAc) modification in neuropathic pain mice. OGT overexpression could impede the therapeutic effects of SA on neuropathic pain. Further investigation revealed that Toll-like receptor 3 (TLR3), stabilized by OGT-induced O-GlcNAc modification, could activate the Mitogen activated protein kinase (MAPK) signaling pathway. Further in vivo experiments demonstrated that TLR3-mediated p38 mitogen-activated protein kinase (p38MAPK) activation is involved in SA-mediated relief of neuropathic pain. In conclusion, this study uncovers a novel molecular pathway deactivated by SA treatment in neuropathic pain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hydraulic fracturing (HF) has substantially boosted global unconventional hydrocarbon production but has also introduced various environmental and operational challenges. Understanding the interactions between abundant and diverse microbial communities and chemicals, particularly polymers used for proppant delivery, thickening, and friction reduction, in HF water cycles is crucial for addressing these challenges. This review primarily examined the recent studies conducted in China, an emerging area for HF activities, and comparatively examined studies from other regions. In China, polyacrylamide (PAM) and its derivatives products became key components in hydraulic fracturing fluid (HFF) for unconventional hydrocarbon development. The microbial diversity of unconventional HF water cycles in China was higher compared to North America, with frequent detection of taxa such as Shewanella, Marinobacter, and Desulfobacter. While biodegradation, biocorrosion, and biofouling were common issues across regions, the mechanisms underlying these microbe-polymer interactions differed substantially. Notably, in HF sites in the Sichuan Basin, the use of biocides gradually decreased its efficiency to mitigate adverse microbial activities. High-throughput sequencing proved to be a robust tool that could identify key bioindicators and biodegradation pathways, and help select optimal polymers and biocides, leading to more efficient HFF systems. The primary aim of this study is to raise awareness about the interactions between microorganisms and polymers, providing fresh insights that can inform decisions related to enhanced chemical use and biological control measures at HF sites., Competing Interests: Declaration of competing interest Cheng Zhong reports financial support was provided by Southwest Petroleum University. If there are other authors, they 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.)

Mild autophagy accompanied with immunogenic cell death (ICD) effect destructs immune-associated antigens, weakening the immune response against tumor growth. To address this dilemma, we develop a peptide-based bicomponent nanocarrier with encapsulation of a cellular hyperautophagy activator (STF-62247) for near-infrared (NIR) photo/immunotherapy to eliminate primary and metastatic breast tumors. The electrostatic-driven nanodrug (PPNPs@STF) with active-targeting and efficient endosomal escape can induce specific ICD effect upon NIR laser irradiation, and trigger autophagy to a mild activation state. Notably, the simultaneously released STF-62247 precisely promotes autophagy to an overactivated state, resulting in autophagic death of tumor cells and further boosting ICD-related antigen presentation. More importantly, the combined photo/immunotherapy of PPNPs@STF not only inhibits tumor cell proliferation, but also promotes dendritic cells (DCs)-associated immune response. In 4 T1 tumor-bearing mice, PPNPs@STF effectively inhibits growth of primary and distant tumors, and suppresses lung metastasis with a minimized side effect. This study provides a hyperautophagy activator-assisted strategy that can enhance ICD-based antitumor immune response for the treatment of metastatic breast cancer., 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.)

Heavy metals contained in waste activated sludge (WAS), especially zinc ions, have an inhibitory effect on the anaerobic digestion. However, the effects of zinc ions on digester performance, antibiotic resistance genes (ARGs) reduction, and the microbial community involved in the anaerobic mesophilic co-digestion (AcoD) of WAS and food waste (FW) have not been fully characterized. Therefore, batch trials and continuous stirred tank reactors were used under different zinc-ion concentrations. Findings showed that the AcoD system can tolerate a maximum zinc ion of 540 mg/L in a short-term batch and 470 mg/L in a long-term AcoD system, promoting methane production of approximately 1.0-17.0 %. Metagenomic analysis revealed that syntrophic H 2 transfer occurred between Syntrophomonas and Methanoculleus and the aceticlastic and hydrogenotrophic methanogenic pathways were both enhanced by 1.18- and 1.16 times, respectively. Moreover, the relative abundance of Methanosarcina increased from 58.4 % to 72.5 % at 470 mg/L to adapt to the high zinc ion concentration during long-term continuous operation. These results revealed that AcoD with a low zinc ion concentration can effectively increase the removal percentage of ARGs. The results provide guidance for biogas recovery and use of mesophilic AcoD with FW and WAS containing high zinc ion concentrations without pretreatment process., 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.)

Pinelliae Rhizoma is a key ingredient in botanical supplements and is often adulterated by Rhizoma Pinelliae Pedatisectae, which is similar in appearance but less expensive. Accurate identification of these materials is crucial for both scientific and commercial purposes. Traditional morphological identification relies heavily on expert experience and is subjective, while chemical analysis and molecular biological identification are typically time consuming and labor intensive. This study aims to employ a simpler, faster, and non-invasive image recognition technique to distinguish between these two highly similar plant materials. In the realm of image recognition, we aimed to utilize the vision transformer (ViT) algorithm, a cutting-edge image recognition technology, to differentiate these materials. All samples were verified using DNA molecular identification before image analysis. The result demonstrates that the ViT algorithm achieves a classification accuracy exceeding 94%, significantly outperforming the convolutional neural network model's 60%-70% accuracy. This highlights the efficiency of this technology in identifying plant materials with similar appearances. This study marks the pioneer work of the ViT algorithm to such a challenging task, showcasing its potential for precise botanical material identification and setting the stage for future advancements in the field., (© 2024 Institute of Food Technologists.)

Photodynamic therapy (PDT) is demonstrated to be effective in inducing antitumor immune responses for tumor metastasis treatment. However, tumor hypoxia, inferior tissue penetration of light, and low singlet oxygen ( 1 O 2 ) quantum yield significantly hamper the efficacy of PDT, thus weakening its immune function. Moreover, PDT-mediated neutrophil extracellular traps (NETs) formation can further reduce the therapeutic effectiveness. Herein, the use of defect-rich CoMo-layered double hydroxide (DR-CoMo-LDH) nanosheets as a carrier to load a typical peptidyl arginine deiminase 4 inhibitor, i.e., YW4-03, to construct a multifunctional nanoagent (403@DR-LDH) for PDT/immunotherapy, is reported. Specifically, 403@DR-LDH inherits excellent 1 O 2 generation activity under 1550 nm laser irradiation and improves the half-life of YW4-03. Meanwhile, 403@DR-LDH plus 1550 nm laser irradiation can stimulate immunogenic cell death to promote the maturation of dendric cells and activation/infiltration of T cells and significantly downregulate H3cit protein expression to inhibit NETs formation, synergistically promoting the antitumor metastasis effect. Taken together, 403@DR-LDH can kill cancer cells and inhibit tumor growth/metastasis under 1550 nm laser irradiation. Single-cell analysis indicates that 403@DR-LDH can regulate the ratio of immune cells and immune-related proteins to improve the tumor immune microenvironment, showing strong efficacy to inhibit the tumor growth, metastasis, and recurrence., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Purpose: To analyze the characteristics of cerebral blood flow changes of poor sleep quality in people with epilepsy(PWE)., Methods: 90 PWE treated in The General Hospital of Ningxia Medical University from December 2021 to September 2023 were divided into poor sleep quality group (PSQG) and good sleep quality group (GSQG) according to the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), to compare the differences in cerebral perfusion between the two groups of patients, so as to summarize the characteristics of cerebral blood flow changes of poor sleep quality in PWE., Results: The positive rate of interictal single-photon emission computed tomography/computed tomography (SPECT/CT) was 76.7 %(69/90), which showed localized cerebral hypoperfusion. There was no statistical difference between the two groups of PSQG (N=29) and GSQG (N=61) in terms of the positive rate of SPECT/CT, the number of hypoperfusion foci, and the range of hypoperfusion foci. In PSQG and GSQG, 9 patients(31.0 %) and 6 patients(9.8 %) showed hypoperfusion in the right parietal lobe, respectively, and the difference between the two groups was statistically significant (P=0.017). There was no statistical difference the rate of the interictal epileptiform discharges (IEDs) and the brain area of IEDs in electroencephalography(EEG) between the two groups., Conclusion: SPECT/CT of poor sleep quality in PWE demonstrated hypoperfusion in the right parietal lobe., 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 Inc. All rights reserved.)

Hearing loss is a common chronic sensory deficit that affects millions of people worldwide and has emerged as a significant public health concern. The association between environmental exposure to chemicals and the prevalence of hearing impairment has recently attracted increased attention. Chlorinated paraffins (CPs) are a type of chemical compound that has been widely used and commonly detected in samples of both environmental and human origin. The knowledge of the toxicological effects of CPs, particularly its ototoxicity, remains limited at present. In this study, six commercial CPs were selected and evaluated using cochlea hair HEI-OC1 cells for their cytotoxicity, apoptosis, DNA damage, reactive oxygen species (ROS) accumulation and oxidative response. The cytotoxicity was observed after CPs exposure at high concentrations except for C-40 and was positively related to the chlorine content (Cl-content) in both CCK-8 and trypan blue assays. All 6 CPs induced cells apoptosis through caspase-dependent apoptotic pathway. CPs exposure induced DNA damage and stimulated ROS overproduction. Antioxidant N-acetyl-L-cysteine (NAC) could reverse the cytotoxicity and ROS accumulation caused by CPs exposure. The overexpression of ATF4 and CHOP indicated that endoplasmic reticulum (ER) stress was involved in the CPs induced cytotoxicity. Thus, CPs induced cytotoxicity and apoptosis via ROS accumulation, ER stress and DNA damage and positively related to the Cl-content and our findings indicate that CPs may pose a risk of ototoxicity at environmental relevant exposure levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent years, antibody-drug conjugate (ADC) technology, which uses monoclonal antibodies (mAbs) to specifically deliver effective cytotoxic payloads to tumor cells, has become a promising method of tumor targeted therapy. ADCs are a powerful class of biopharmaceuticals that link antibodies targeting specific antigens and small molecule drugs with potent cytotoxicity via a linker, thus enabling selective destruction of cancer cells while minimizing systemic toxicity. DXd is a topoisomerase I inhibitor that induces DNA damage leading to cell cycle arrest, making it an option for ADC payloads. The DXd-ADC technology, developed by Daiichi Sankyo, is a cutting-edge platform that produces a new generation of ADCs with improved therapeutic metrics and has shown significant therapeutic potential in various types of cancer. This review provides a comprehensive assessment of drugs developed with DXd-ADC technology, with a focus on mechanisms of action, pharmacokinetics studies, preclinical data, and clinical outcomes for DS-8201a, U3-1402, DS-1062a, DS-7300a, DS-6157a, and DS-6000a. By integrating existing data, we aim to provide valuable insights into the current therapeutic status and future prospects of these novel agents., 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 Inc. All rights reserved.)

Background: The lifelong administration of immunosuppressants remains the largest drawback in vascularized composite allotransplantation (VCA). Therefore, developing alternative strategies to minimize the long-term use of immunosuppressive agents is crucial. This study investigated whether full-spectrum bright light therapy (FBLT) combined with short-term immunosuppressant therapy could prolong VCA survival in a rodent hindlimb model., Methods: Hindlimb allotransplantation was conducted from Brown-Norway to Lewis rats, and the rats were divided into 4 groups. Group 1 did not receive treatment as a rejection control. Group 2 received FBLT alone. Group 3 was treated with short-term antilymphocyte serum (ALS) and cyclosporine A (CsA). Group 4 was administered short-term ALS/CsA combined with FBLT for 8 weeks. Peripheral blood and transplanted tissues were collected for analysis., Results: The results revealed median survival time of FBLT alone (group 2) did not increase allograft survival compared with the control (group 1). However, in group 4, FBLT combined with short-term ALS/CsA, median composite tissue allograft survival time (266 days) was significantly prolonged compared with groups 1 (11 days), 2 (10 days), and 3 (41 days) ( P < 0.01). Group 4 also showed a significant increase in regulatory T cells ( P = 0.04) and transforming growth factor-β1 levels ( P = 0.02), and a trend toward a decrease in interleukin-1β levels ( P = 0.03) at 16 weeks after transplantation as compared with control (group 1)., Conclusions: FBLT combined with short-term immunosuppressants prolonged allotransplant survival by modulating T-cell regulatory functions and antiinflammatory cytokine expression. This approach could be a potential strategy to increase VCA survival., Clinical Relevance Statement: Full-spectrum light therapy could be a potential strategy to increase vascularized composite allotransplant survival., (Copyright © 2023 by the American Society of Plastic Surgeons.)

The effects of Pueraria lobata polysaccharide (PPL-1) on osteoarthritis (OA) disease were comprehensively evaluated by using chondrocytes and synoviocytes extracted from the joints of SD rats based on in vitro cell experiments and by establishing pathological models of OA rats. The results showed that concentrations of 1.25-10 and 0.2-1.6 μg/mL, PPL-1 did not inhibit or promote chondrocytes and synoviocytes in vitro. However, at concentrations of 1.25-10 and 0.2-1.6 μg/mL, it can promote cartilage and synovial membrane cells after LPS stimulation of cell activity and inhibite LPS-induced apoptosis. The results of animal experiments showed that PPL-1 can reduce the symptoms of joint swelling in OA rats, decrease the production of serum inflammatory cytokines TNF-α, IL-1β, and IL-6, and slow down the occurrence of inflammation. Therefore, from the perspective of symptoms, inflammatory factors and pathology, PPL-1 has therapeutic effects on OA rats and alleviates the development of inflammation. It indicated that PPL-1 has the potential to be developed into an OA therapeutic drug with anti-inflammatory properties that protects and activates chondrocytes., 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/or company that could be constructed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Eighteen compounds including eleven previously undescribed diterpenes were isolated from the leaves of Croton mangelong. The structures were determined by HRESIMS, IR, NMR, X-ray diffraction and ECD spectroscopic analysis. All isolates were assayed for their anti-hyperglycemic activities in insulin resistance (IR) 3T3-L1 adipocytes, and compound 4 was tested for its anti-diabetic activity in vivo. Results suggested compound 4 could effectively reduce blood glucose level in diabetic SD rats in a dose of 30 mg/kg., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The adverse effects of traditional pharmaceutical immunosuppressive regimens have been a major obstacle to successful allograft survival in vascularized composite tissue allotransplantation (VCA) cases. Consequently, there is a pressing need to explore alternative approaches to reduce reliance on conventional immunotherapy. Cell therapy, encompassing immune-cell-based and stem-cell-based regimens, has emerged as a promising avenue of research. Immune cells can be categorized into two main systems: innate immunity and adaptive immunity. Innate immunity comprises tolerogenic dendritic cells, regulatory macrophages, and invariant natural killer T cells, while adaptive immunity includes T regulatory cells and B regulatory cells. Investigations are currently underway to assess the potential of these immune cell populations in inducing immune tolerance. Furthermore, mixed chimerism therapy, involving the transplantation of hematopoietic stem and progenitor cells and mesenchymal stem cells (MSC), shows promise in promoting allograft tolerance. Additionally, extracellular vesicles (EVs) derived from MSCs offer a novel avenue for extending allograft survival. This review provides a comprehensive summary of cutting-edge research on immune cell therapies, mixed chimerism therapies, and MSCs-derived EVs in the context of VCAs. Findings from preclinical and clinical studies demonstrate the tremendous potential of these alternative therapies in optimizing allograft survival in VCAs., Competing Interests: Declaration of competing interest None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

A novel cis-diol-microporous organic networks (MONs-2OH) material was synthesized via room temperature and Sonogashira coupling reactions, which exhibits exceptional adsorption properties for catecholamines (CAs). MONs-2OH demonstrates robust hydrogen bonding and π-π stacking interactions, crucial for effective adsorption. The MONs-2OH was incorporated into pipette tip solid-phase extraction and developed a new method for detecting CAs in human urine using HPLC-MS/MS. Characterization of the adsorbent revealed its high stability, large specific surface area, abundant phenolic hydroxyl groups, rapid extraction speed, and superior adsorption efficiency. The method achieved a wide linear range (0.5-500 ng/mL), low detection limits (0.06-0.26 ng/mL), high accuracy (90.4 %-99.4 %), and excellent precision (RSD ≤ 10 %). Comparative studies showed MONs-2OH outperforms commercial adsorbents in terms of recovery and adsorption capacity. The results underscore the potential of MONs-2OH for rapid and sensitive CAs determination, offering significant advantages for the auxiliary diagnosis of depression and enhancing the application of PT-SPE in sample pretreatment., 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.)

Noninvasive pharmacological strategies like nicotinamide mononucleotide (NMN) supplementation can effectively address age-related ovarian infertility by maintaining or enhancing oocyte quality and quantity. This study revealed that ovarian nicotinamide adenine dinucleotide levels decline with age, but NMN administration significantly restores these levels, preventing ovarian atrophy and enhancing the quality and quantity of ovulated oocytes. Improvements in serum hormone secretion and antioxidant factors, along with decreased expression of proinflammatory factors, were observed. Additionally, a significant increase in the number of ovarian follicles in aging individuals was noted. Scanning electron microscopy data indicated that NMN significantly alters the density and morphology of lipid droplets and mitochondria in granulosa cells, suggesting potential targets and mechanisms. Transcriptomic analysis and validation experiments collectively suggested that the beneficial effects of NMN on aging ovaries are mediated through enhanced mitochondrial function, improved energy metabolism, and reduced inflammation levels. Our results suggest that NMN supplementation could improve the health status of aging ovaries and enhance ovarian reserve, offering new insights into addressing fertility challenges in older women through assisted reproductive technology., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

To explore the predictive value of traditional machine learning (ML) and deep learning (DL) algorithms based on computed tomography pulmonary angiography (CTPA) images for short-term adverse outcomes in patients with acute pulmonary embolism (APE). This retrospective study enrolled 132 patients with APE confirmed by CTPA. Thrombus segmentation and texture feature extraction was performed using 3D-Slicer software. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature dimensionality reduction and selection, with optimal λ values determined using leave-one-fold cross-validation to identify texture features with non-zero coefficients. ML models (logistic regression, random forest, decision tree, support vector machine) and DL models (ResNet 50 and Vgg 19) were used to construct the prediction models. Model performance was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). The cohort included 84 patients in the good prognosis group and 48 patients in the poor prognosis group. Univariate and multivariate logistic regression analyses showed that diabetes, RV/LV ≥ 1.0, and Qanadli index form independent risk factors predicting poor prognosis in patients with APE(P < 0.05). A total of 750 texture features were extracted, with 4 key features identified through screening. There was a weak positive correlation between texture features and clinical parameters. ROC curves analysis demonstrated AUC values of 0.85 (0.78-0.92), 0.76 (0.67-0.84), and 0.89 (0.83-0.95) for the clinical, texture feature, and combined models, respectively. In the ML models, the random forest model achieved the highest AUC (0.85), and the support vector machine model achieved the lowest AUC (0.62). And the AUCs for the DL models (ResNet 50 and Vgg 19) were 0.91 (95%CI: 0.90-0.92) and 0.94(95%CI: 0.93-0.95), respectively. Vgg 19 model demonstrated exceptional precision (0.93), recall (0.76), specificity (0.95) and F1 score (0.84). Both ML and DL models based on thrombus texture features from CTPA images demonstrated higher predictive efficacy for short-term adverse outcomes in patients with APE, especially the random forest and Vgg 19 models, potentially assisting clinical management in timely interventions to improve patient prognosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Dysbiosis of the microbiome is a key hallmark of polycystic ovary syndrome (PCOS). However, the interaction between the host and microbiome and its relevance to the pathogenesis of PCOS remain unclear., Methods: To evaluate the role of the commensal gut microbiome in PCOS, we gavaged germ-free mice with the fecal microbiota from patients with PCOS or healthy individuals and evaluated the reproductive endocrine features of the recipient mice., Results: Mice transplanted with fecal microbiota from PCOS patients and those transplanted from healthy controls presented different bacterial profiles and reproductive endocrine features. The fecal microbiota of the mice in the PCOS group was enriched in Phocaeicola, Mediterraneibacter, Oscillospiraceae, Lawsonibacter and Rikenellaceae. Fecal microbiota transplantation (FMT) from PCOS patients induced increased disruption of ovarian functions, lipo-metabolic disturbance, insulin resistance and an obese-like phenotype in recipient mice., Conclusion: Our findings suggest that the microbiome may govern the set point of PCOS-bearing individuals and that gut ecosystem manipulation may be a useful marker and target for the management of PCOS., (© 2024. The Author(s).)

The failure or delay in healing of critical bone defects is primarily due to early local anoxic conditions and reduced osteogenic activity. In this research, we integrated calcium peroxide (CPO) embedded polycaprolactone (PCL) microspheres and osteoinductive nanoparticles (Hydroxyapatite/Laponite) into a thermosensitive hydrogel (Pluronic F127), thereby formulating an injectable oxygen-releasing osteogenic thermosensitive hydrogel. Notably, the oxygen-releasing microspheres (ORMs) within the composite hydrogel provide stable oxygen release for up to 21 days, ensuring the survival, migration, and bioactivity of both mesenchymal stem cells and endothelial cells under anoxic conditions. Additionally, the composite hydrogel significantly augments the osteogenic potential of bone marrow mesenchymal stem cells by providing a biomimetic microenvironment with the incorporation of nano-hydroxyapatite/laponite. Ultimately, the injectable composite hydrogel successfully stimulated bone regeneration within a cranial defect in a rat model after 8 weeks, with enhanced vascularization and bone quality. The engineered hydrogel provides a minimally invasive approach to stimulate bone regeneration with a sustained oxygen supply and osteogenic microenvironment provision, underlining its potential for treating critical bone defects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Microplastics (MPs) are widespread ocean pollutants and many studies have explored their effects. However, research on MPs combined impact with copper (Cu) on dimethylated sulfur compound production is limited. Dimethyl sulfide (DMS) is an important biogenic sulfur compound related to global temperatures. This study examined the ecotoxicological effects of polyamide 6 MPs and Cu on dimethylsulfoniopropionate (DMSP), DMS, and dimethyl sulfoxide (DMSO) production in Manila clams (Ruditapes philippinarum). Our findings showed that MPs and Cu increased oxidative stress, indicated by higher superoxide anion radical production and malondialdehyde levels while decreasing glutathione contents and increasing superoxide dismutase activities. Additionally, MPs and Cu exposure reduced DMS and dissolved DMSO (DMSO d ) concentrations due to decreased grazing. These results contribute to a better understanding of the ecotoxicological effects of MPs/Cu on bivalves and their roles in the organic sulfur cycle, suggesting a need for further research on long-term impacts on them., 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 Ltd.)

Metastasis is the main cause of death in cancer patients, the lung is one of the most common metastatic organs of malignant solid tumors. Before tumor cells metastasize to the lungs, they interact with immunosuppressive cells, alveolar epithelial cells, and lung fibroblasts to form a pre-metastatic niche. The pre-metastatic niche is a key factor leading to tumor cell metastasis to the lungs. Research has found that traditional Chinese medicine and its components can inhibit the formation of pre-metastatic niche. Therefore, this article reviewed the research progress on the formation of lung pre-metastatic niche and the intervention of traditional Chinese medicine in pulmonary PMN, in order to provide new Chinese medicine prescriptions and research ideas for further clinical prevention and treatment of tumor metastasis to the lung., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Polyvinyl chloride (PVC) microplastics present in sewage were trapped in sludge, thereby hindering anaerobic digestion performance of waste active sludge (WAS). Phages regulate virocell metabolism by encoding auxiliary metabolic genes (AMGs) related to energy acquisition and material degradation, supporting hosts survive in harsh environments and play a crucial role in biogeochemical cycles. This study investigated the potential effects of phages on the recovery of WAS anaerobic digestion under PVC stress. We observed a significant alteration in the phage community induced by PVC microplastics. Phages encoded AMGs related to anaerobic digestion and cell growth probably alleviate PVC microplastics inhibition on WAS anaerobic digestion, and 54.2 % of hydrolysis-related GHs and 40.8 % of acidification-related AMGs were actively transcribed in the PVC-exposed group. Additionally, the degradation of chitin and peptidoglycan during hydrolysis and the conversion of glucose to pyruvate during acidification were more susceptible to phages. Prediction of phage-host relationship indicated that the phyla Pseudomonadota were predominantly targeted hosts by hydrolysis-related and acidification-related phages, and PVC toxicity had minimal impact on phage-host interaction. Our findings highlight the importance of phages in anaerobic digestion and provide a novel strategy for using phages in the functional recovery of microplastic-exposed sludge., 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.)

Debris flows are a prevalent mountain hazard that poses severe risks to human life and property. Debris-flow hazard assessments at the regional scale are vital for risk management, which establish spatial associations between debris flows and their influencing factors based on specific evaluation units. Different spatial scales of evaluation units can influence the spatial attributes and associations obtained by statistics, and further affect the accuracy of hazard assessments. However, there is limited consensus regarding the optimal spatial scale of evaluation units for debris-flow hazard assessment. To address this issue, six different scales of grid cells and forty influencing factors related to topography, material sources, hydrology, and human activities are analyzed by the geographical detector model to assess the debris-flow hazards in the Dadu River basin, China. The results reveal that over 92 % of debris-flow points fall within hazardous zones across all spatial scales, confirming the effectiveness of the assessment model. Topography, particularly local gully topography, dominates the debris-flow occurrence in the study area, while human activities also significantly contribute. As the spatial scale of evaluation units increases, the explanatory power of the influencing factors improves, with the 90 % quantile ranging from 0.23 to 0.46. This result suggests that larger spatial scales weaken the spatial characteristics of the factors. The finer and more informative the factors are, the more sensitive to spatial scale effects. The 10 km × 10 km is identified as the optimal spatial scale, which effectively preserves the local spatial characteristics while avoiding information loss or overload. These findings provide valuable insights for enhancing the accuracy of hazard assessments and improving the efficiency of risk management., 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.)

To explore the feasibility and application value of texture analysis based on computed tomography (CT) for predicting the differentiation of esophageal squamous cell carcinoma (ESCC). Patients diagnosed with ESCC who underwent chest contrast-enhanced CT before treatment were selected. Based on the pathological results, the patients were stratified into poorly differentiated and moderately well-differentiated groups. FireVoxel software was used to analyze the region of interest based on venous phase CT images. Texture parameters including the mean, median, standard deviation (SD), inhomogeneity, skewness, kurtosis, and entropy were obtained automatically. Differences in the texture parameters and their relationship with the degree of differentiation between the 2 groups were analyzed. The value of CT texture parameters in identifying poor differentiation and moderate-well differentiation of esophageal cancer was analyzed using the ROC curve. A total of 48 patients with ESCC were included, including 24 patients in the poorly differentiated group and 24 patients in the moderate-well-differentiated group. There were negative correlations between SD, inhomogeneity, entropy, and the degree of differentiation of esophageal cancer (P < .05). The correlation of inhomogeneity was the highest (r = -0.505, P < .001). SD, inhomogeneity, and entropy could effectively distinguish between the poorly and moderately well-differentiated groups, with statistically significant differences between the 2 groups (P < .05). The best critical values for SD, inhomogeneity, and entropy were 17.538, 0.017, and 3.917, respectively. The areas under the ROC curve were 0.793, 0.792, and 0.729, respectively, with the SD and inhomogeneity being the best. The application of texture analysis on venous phase CT images holds promise as a method for forecasting the degree of differentiation in esophageal cancers, which could significantly contribute to the preoperative noninvasive evaluation of tumor differentiation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Elucidating the correlations between the core structure of atomically precise nanoclusters and their catalytic activities is fundamentalfor exploring highly efficient nanocatalysts. Herein, a series of Ag-based nanoclusters protected by 2,4-dimethylphenylthiophenol (specifically Ag 4 Pd 2 (SPhMe 2 ) 8 and Ag 24 M(SPhMe 2 ) 18 where M = Ag, Pd, and Pt) were synthesized and deposited on TiO 2 supports as heterogeneous catalysts for the selective hydrogenation of nitroarenes with NaBH 4 as the reductant. It was found that Ag 4 Pd 2 (SPhMe 2 ) 8 could spontaneously lose its ligands during catalysis, leading to the formation of polydispersed AgPd nanoparticles. This transformation endows the system with extraordinary activity for driving the hydrogenation of nitroarenes. However, the Ag 24 M (M = Ag, Pd, and Pt) systems, maintain their core structures during catalysis. They follow the generally reported ligand-mediated hydride-involved process, with catalytic activities depending on the central atom (Pt > Pd > Ag), which affects the hydride transferred from the nanoclusters to the reactant to regulate the catalysis.

Background: Intra-articular administration of mesenchymal stem cells (MSCs) presents a novel methodology for managing osteoarthritis, but there is still no definite evidence of its efficacy., Aim: To assess the comparative effectiveness of MSCs and platelet-rich plasma (PRP) for managing osteoarthritis by reviewing the literature and using meta-analysis., Methods: Randomized controlled trials and cohort studies comparing MSCs and PRP for managing osteoarthritis were included. We searched 'osteoarthritis', 'mesenchymal stem cell', 'platelet-rich plasma', and other words in Pubmed, Embase, and Cochrane Library database. The search period encompassed the entire duration of the databases, starting from its inception until April 2024. Two researchers conducted the literature search, extracting data, and evaluating quality as distinct processes. Meta-analysis was carried out using the software RevMan5.3, and the calculation of weighted mean difference (WMD) and 95% confidence interval (CI) were performed using either a fixed-effect model or a random-effects model., Results: Eleven studies were included, comprising 8 randomized controlled trials and 3 cohort studies. A total of 693 individuals participated in the study, of which 394 received intra-articular injections of MSCs (group A) and 299 received intra-articular injections of PRP (group B). The two groups were comparable in the five dimensions of knee injury and osteoarthritis outcome score (KOOS) [pain (WMD: 0.38, 95% CI: -3.62 to 4.38, P > 0.05), symptoms (WMD: -1.48, 95% CI: -5.90 to 2.94, P > 0.05), activities of daily living (ADL, WMD: -2.36, 95% CI: -6.87 to 2.14, P > 0.05), function in sport and recreation (Sport/Rec, WMD: -3.84, 95% CI: -10.60 to 2.92, P > 0.05), knee-related quality of life (QOL, WMD: 0.09, 95% CI: -5.48 to 5.67, P > 0.05)] and Western Ontario and McMaster Universities osteoarthritis index (WOMAC, WMD: 0.47, 95% CI: -3.76 to 4.70, P > 0.05). Compared with group A, the International Knee Documentation Committee Subjective Knee Form (IKDC, WMD: 4.19, 95% CI: 2.57 to 5.82, P < 0.001) score of group B was higher., Conclusion: The short-term effectiveness of intra-articular administration of PRP for managing osteoarthritis is slightly better than that of MSCs. However, because of the limited quantity of incorporated research studies and the potential for bias, requisite in the future are studies of substantial size and superior quality., Competing Interests: None., (AJTR Copyright © 2024.)

Urbanization has facilitated economic development while simultaneously resulting in various ecological issues. Constructing a multi-scale nested and composite functional urban-rural ecological network is crucial for improving ecological security. This study utilizes Dali City as a case study and employs methods including MSPA, circuit theory, and landscape connectivity index to develop the urban-rural habitat network, water green network, and recreation network, focusing on the " red-green-blue " spatial framework. An analysis of the spatial characteristics of source areas, corridors, ecological strategic points, and other spatial elements is conducted to establish a multi-level, multi-objective, and multifunctional composite urban-rural ecological network. The results show that: (1) 13 ecological source areas were identified in both the municipal and main urban areas, along with 22 ecological corridors in the municipal and 20 main urban areas. The distribution of ecological corridors was uniform across the study area. (2) The optimal width for the municipal biological corridor is 150 m, the main urban area should have a width of 90 m. The optimal width for rainwater corridors in municipal and main urban areas is 60 m. (3) The multi-scale nested ecological network identified 4 common ecological sources, 11 ecological corridors, 3 rainwater corridors, 6 wetland nodes, and 7 amusement nodes. Overall, the number of ecological nodes is limited, indicating a need for enhanced node construction. The research findings offer insights for developing ecological networks that integrate urban and rural functions, serving as a reference for ecological protection and restoration in pertinent regions., Competing Interests: There is no declaration of interest., (© 2024 The Authors.)

Wearable devices hold significant potential in healthcare and medical diagnostics. One major challenge in realizing this potential is the low barrier property of polymer substrates, which fail to withstand surrounding moisture and biofluids. In this work, a two-step strategy involving ALI followed by a UV-curing process is developed to fabricate a K 48 PDMS/Al 2 O 3 ultra-barrier with high barrier property of 7.82 × 10 -5 g m -2 day -1 under stretching strain, representing one of the highest values among current works. Moreover, the K 48 PDMS/Al 2 O 3 barrier enables Ca-tested devices to exhibit extended operational lifetimes of up to 12 days in simulated rain. It also ensures the high sensitivity of strain sensors for real-time monitoring of health-related physiological signals, even when exposed to aggressive solutions such as PBS, KOH, and glucose. A clear "filling-cross-linking" mechanism is revealed, involving the filling of the void spaces within polymer chains followed by the cross-linking of polymer side chains to enhance the density of the hybrid layer. Adjusting porosity and functional group density ensures complete Al 2 O 3 infiltration into the polymer. The cross-linking increases from 12.31% to 73.79% compared to the UV-curing process alone due to the presence of Al 2 O 3 , further enhancing the density of the hybrid layer and its barrier properties. The proposed strategy in our work shows great potential for providing highly reliable encapsulation for wearable electronics.

Plant non-specific lipid transfer protein (nsLTP) is able to bind and transport lipids and essential oils, as well as engage in various physiological processes, including defense against phytopathogens. Kalanchoe fedtschenkoi (Lavender Scallops) is an attractive and versatile succulent. To investigate the functional mechanism of Kalanchoe fedtschenkoi nsLTP (Ka-nsLTP), we expressed, purified and successfully obtained monomeric Ka-nsLTP. Mutational experiments revealed that the C6A variant retained the same activity as the wild-type (WT) Ka-nsLTP. Ka-nsLTP showed weak antiphytopathogenic bacterial activity, but inhibited fungal growth. Ka-nsLTP possessed a hydrophobic cavity effectively binding lauric acid. Our results offer novel molecular insights into the functional mechanism of nsLTP, which broadens our knowledge of the biological function of nsLTP in crops and provides a useful locus for genetic improvement of plants., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

1,4-Naphthoquinone scaffold-derived compounds has shown considerable pharmacological properties against cancer, including acute myeloid leukemia (AML) However, its impact and mechanisms in AML are uncertain. In this study, the mechanisms of 1,4-naphthoquinone scaffold-derived compounds against AML were investigated via network pharmacology, molecular docking and molecular dynamics simulation. ASINEX database was used to collect the 1,4-naphthoquinone scaffold-derived compounds, and compounds were extracted from the software to evaluate their drug similarity and toxicity. The potential targets of compounds were retrieved from the SwissTargetPrediction Database and the Similarity Ensemble Approach Database, while the potential targets of AML were obtained from the GeneCards databases and Gene Expression Omnibus. The STRING database was used to construct a protein-protein interaction (PPI) network, topologically and Cyto Hubb plugin of Cytoscape screen the central targets. After selecting the potential key targets, the gene ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for the intersection targets, and a network map of "compounds-potential targets-pathway-disease" were constructed. Molecular docking of the compounds with the core target was performed, and core target with the strongest binding force and 1,4-naphthoquinone scaffold-derived compounds was selected for further molecular dynamics simulation and further molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) approach verification. In addition, the Bloodspot database was applied to perform the overall survival of core targets. A total of 19 1,4-naphthoquinone scaffold-derived compounds were chosen out, and then 836 targets of compounds, 96 intersection targets of AML were screened. Core targets include STAT3, TLR4, HSP90AA1, JUN, MMP9, PTPRC, JAK2, PTGS2, KIT and CSF1R. GO functional enrichment analysis revealed that 90 biological processes, 10 cell components and 12 molecular functions were enriched while KEGG pathway enrichment analysis revealed 34 enriched signaling pathways. Analysis of KEGG enrichment hinted that these 10 core genes were located in the pathways in cancer, suggesting that 1,4-naphthoquinone scaffold-derived compounds had potential activity against AML. Molecular docking analysis revealed that the binding energies between 1,4-naphthoquinone scaffold-derived compounds and the core proteins were all higher than - 6 kcal/mol, indicating that the 10 core targets all had strong binding ability with compounds. Moreover, a good binding capacity was inferred from molecular dynamics simulations between compound 7 and MMP9. The total binding free energy calculated using the MM/GBSA approach revealed values of - 6356.865 kcal/mol for the MMP9-7 complex. In addition, Bloodspot database results exhibited that HSP90AA1, MMP9 and PTPRC were associated with overall survival. The findings provide foundations for future studies into the interaction underlying the anti-AML potential of compounds with 1,4-naphthoquinone-based scaffold structures. Compounds with 1,4-naphthoquinone-based scaffold structures exhibits considerable potential in mitigating and treating AML through multiple targets and pathways., (© 2024. The Author(s).)

The Caesalpinioideae subfamily contains many well-known trees that are important for economic sustainability and human health, but a lack of genomic resources has hindered their breeding and utilization. Here, we present chromosome-level reference genomes for the two food and industrial trees Gleditsia sinensis (921 Mb) and Biancaea sappan (872 Mb), the three shade and ornamental trees Albizia julibrissin (705 Mb), Delonix regia (580 Mb), and Acacia confusa (566 Mb), and the two pioneer and hedgerow trees Leucaena leucocephala (1338 Mb) and Mimosa bimucronata (641 Mb). Phylogenetic inference shows that the mimosoid clade has a much higher evolutionary rate than the other clades of Caesalpinioideae. Macrosynteny comparison suggests that the fusion and breakage of an unstable chromosome are responsible for the difference in basic chromosome number (13 or 14) for Caesalpinioideae. After an ancient whole-genome duplication (WGD) shared by all Caesalpinioideae species (CWGD, ∼72.0 million years ago [MYA]), there were two recent successive WGD events, LWGD-1 (16.2-19.5 MYA) and LWGD-2 (7.1-9.5 MYA), in L. leucocephala. Thereafter, ∼40% gene loss and genome-size contraction have occurred during the diploidization process in L. leucocephala. To investigate secondary metabolites, we identified all gene copies involved in mimosine metabolism in these species and found that the abundance of mimosine biosynthesis genes in L. leucocephala largely explains its high mimosine production. We also identified the set of all potential genes involved in triterpenoid saponin biosynthesis in G. sinensis, which is more complete than that based on previous transcriptome-derived unigenes. Our results and genomic resources will facilitate biological studies of Caesalpinioideae and promote the utilization of valuable secondary metabolites., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ambient operation and large-scale demonstration have limited the implementation and evaluation of anaerobic membrane bioreactors (AnMBRs) for low-strength wastewater treatment. Here, we studied these issues at an AnMBR demo plant that treats domestic wastewater and food waste together at ambient temperatures (7-28 °C). At varied hydraulic retention times (HRTs, 8-42 h), the AnMBR achieved a COD removal efficiency and biogas production of 80.4% ± 3.9% and 66.5 ± 9.4 NL/m 3 -Influent, respectively. Moreover, a stable high membrane flux of 14.4 L/m 2 /h was reached. The electric energy consumption for the AnMBR operation was 0.269-0.433 kW·h/m 3 , and 49.4%-91.3% could be compensated by the electric energy produced from methane production. At an HRT of 10 h, the AnMBR system demonstrated an impressively low net electric energy consumption of merely 0.05 kW·h/m 3 , resulting in a net greenhouse gas emission of 0.015 CO 2 -eq/m 3 , cutting 85% compared to the conventional activated sludge process. Achievements in this study provide key parameters for the ambient operation of AnMBR and demonstrate that AnMBR is an energy-saving and low-carbon solution for low-strength wastewater treatment., 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.)

Canine mammary gland tumour (CMT) is the most common spontaneous tumour in intact female dogs and often exhibits metastases. Auranofin (AF) is a gold complex used for treating rheumatism. The excellent anti-tumour ability of AF has been demonstrated in various types of human and canine tumours. In this study, five CMT cell lines (CIPp, CMT-7364, CHMp, CIPm and CTBp) and three CMT primary cells (G7894, L1883 and L6783) were used to explore the anti-tumour effect of AF on CMT. Two CMT cell lines (CIPp and CMT-7364) were used to search the underlying mechanism of the effect of AF on CMT. The results showed that AF inhibited the growth, migration, invasion, and colony formation abilities of CMT cells. Additionally, the growth of CMT in a 3D cell culture model was effectively suppressed by AF. Furthermore, AF induced cell apoptosis of CMT cells via the PI3K/AKT pathway. In conclusion, AF effectively induces CMT apoptosis by regulating the PI3K/AKT pathway, indicating that AF should be explored as a potential CMT treatment in future studies., (© 2024 John Wiley & Sons Ltd.)

While cisplatin remains a frontline treatment for bladder cancer (BCa), the onset of resistance greatly hampers its effectiveness. RAC3 is closely linked to chemoresistance in cancer cells, but its specific role in cisplatin resistance within BCa is still elusive. RAC3 expression in BCa was analyzed using bioinformatics and quantitative polymerase chain reaction (qPCR). The gene set enrichment analysis (GSEA) identified RAC3-enriched pathways and the correlation between RAC3 and fatty acid synthase (FASN), a gene involved in fatty acid synthesis. Potential upstream transcription factors of RAC3 were predicted and their interaction with RAC3 was confirmed via dual-luciferase and chromatin immunoprecipitation (ChIP) assays. T24/DDP, a cisplatin-resistant BCa cell line, was established to probe into the regulatory role of RAC3 in cisplatin resistance. Cell proliferation was evaluated by colony formation and the IC 50 values after cisplatin treatment were determined using cell counting kit-8 (CCK-8). The levels of free fatty acids and triglycerides (TGs), as well as the expression of DGAT2 and FASN proteins, were measured to gauge the extent of fatty acid synthesis in cells. Elevated expression of RAC3 was observed in BCa and the cisplatin-resistant BCa cells (T24/DDP). The knockdown of RAC3 within T24/DDP cells was demonstrated to counteract cisplatin resistance. Subsequent analyses identified RAC3 as being notably enriched in the fatty acid synthesis pathway, with Kruppel-like factor 1 (KLF1) emerging as a key upstream regulator. The overexpression of RAC3 was correlated with increased cisplatin resistance in T24/DDP cells, an effect that was mitigated by the addition of the FASN inhibitor, Orlistat. Furthermore, the downregulation of KLF1 suppressed RAC3 expression, disrupted fatty acid synthesis, and attenuated cisplatin resistance in T24/DDP cells. Conversely, the co-overexpression of RAC3 counteracted the effects conferred by KLF1 knockdown. Our study has validated that KLF1 activates RAC3 to mediate fatty acid synthesis and promote cisplatin resistance in BCa, suggesting the KLF1/RAC3 axis as a potential target for combating cisplatin-resistant BCa., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Postoperative delirium (POD) is a serious and common complication. The aim of present study is to investigate the diurnal variation of POD and the effects of esketamine in elderly patients., Methods: A randomized, double-blind, placebo-controlled clinical trial with factorial design was conducted. Patients (aged 65 to 85 years) with normal Mini-Mental State Examination (MMSE) score were stratified by age (≤70 vs. >70) and American Society of Anesthesiologists physical status classification (Ⅱ vs. Ⅲ), then randomly assigned to either morning (08:00-12:00) or afternoon (14:00-18:00) noncardiac operation under general anesthesia with or without esketamine administration (0.2 mg/kg). The primary outcome was the incidence of POD (3-Minute Diagnostic Interview for Confusion Assessment Method-defined Delirium, 3D-CAM) on postoperative days 1, 3, and 7. The secondary outcomes were the scores of MMSE and Hospital Anxiety and Depression Scale. The intention-to-treat analysis of the outcomes were performed by generalized estimating equation., Results: Six patients who did not receive an intervention because of canceled operation were excluded after randomization. The datasets containing 426 cases were analyzed following the intention-to-treat principle after handling missing data via multiple imputation method. The incidence of POD declined from about 55% on postoperative day 1 to 31 and 18% on postoperative days 3 and 7, respectively. Afternoon operation [B=-0.583, OR (95% CI) 0.558 (0.319-0.976); P=0.041], but not esketamine, significantly decreased the incidence of POD. Both esketamine and operation time failed to significantly affect MMSE, HAD, and NRS score. There was no interaction among operation time, esketamine, and follow up time., Conclusion: Elderly patients undergoing elective noncardiac surgery in the afternoon displayed lower POD incidence than those operated in the morning. A single low-dose of esketamine before general anesthesia induction failed to significantly decrease the risk of POD but decrease the risk of intraoperative hypotension and emergence agitation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aimed to assess the efficacy of radial extracorporeal shock wave therapy in treating upper limb spasticity after a stroke., Design: Randomized controlled trial., Setting: Zhujiang Hospital of Southern Medical University., Subjects: This study included 95 people with stroke., Intervention: The active ( n  = 47) and sham-placebo ( n  = 48) radial extracorporeal shockwave therapy groups received three treatment sessions (every third day)., Main Measures: The Modified Ashworth Scale, Hmax/Mmax ratio, root mean square, co-contraction ratio, mechanical parameters of the muscle and temperature were measured at baseline and days 2, 5 and 8., Results: Among the 135 potential participants screened, 100 were enrolled and allocated randomly, with 95 participants ultimately being included in the intent-to-treat analysis dataset. The active group showed significantly better improvements in upper limb spasticity and muscle function than did the sham-placebo group. Greater improvements in the Modified Ashworth Scale were observed in the active group than in the sham-placebo group (difference, -0.45; 95% CI, -0.69 to -0.22; P  < 0.001). Moreover, significant differences in root mean square, co-contraction ratio and Hmax/Mmax ratio were observed between the two groups (all P  < 0.001). The mechanical parameters of the biceps muscle were significantly better in the active group than in the sham-placebo group ( P  < 0.001). The active group had a higher temperature than the sham-placebo group, although the difference was not significant ( P  = 0.070)., Conclusions: This study revealed that the treatment with extracorporeal shockwave therapy can relieve upper limb spasticity in people with stroke., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Selective CO 2 photoreduction to C 2 hydrocarbons is significant but limited by the inadequate adsorption strength of the reaction intermediates and low efficiency of proton transfer. Herein, an ameliorative *CO adsorption and H 2 O activation strategy is realized via decorating bismuth oxychloride (BiOCl) nanostructures with different metal (Pt, Pd, and Au) species. Experimental and theoretical calculation results reveal that distinct *CO binding energies and *H acquisition abilities of the metal cocatalysts mediate the CO 2 reduction activity and hydrocarbon selectivity. The relatively moderate *CO adsorption and *H supply over Pd/BiOCl endows it with the lowest free energy to generate *CHO, leading to its highest activity of hydrocarbon production. Specifically, the Pt cocatalyst can efficiently participate in H 2 O dissociation to deliver more *H for facilitating the protonation of the *CHO and *CHOH, thereby favoring CH 4 production with 76.51% selectivity. A lower *H supply over Pd/BiOCl and Au/BiOCl results in a large energy barrier for *CHO or *CHOH protonation and thus a more thermodynamically favored OC─CHO coupling pathway, which endows them with vastly increased C 2 hydrocarbon selectivity of 81.21% and 92.81%, respectively. The understanding of efficient C 2 hydrocarbon production in this study sheds light on how materials can be engineered for photocatalytic CO 2 reduction., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Streptococcus suis is an important zoonotic pathogen, causing cytokine storms of Streptococcal toxic shock-like syndrome amongst humans after a wound infection into the bloodstream. To overcome the challenges of fever and leukocyte recruitment, invasive S. suis must deploy multiple stress responses forming a network and utilize proteases to degrade short-lived regulatory and misfolded proteins induced by adverse stresses, thereby adapting and evading host immune responses. In this study, we found that S. suis encodes multiple ATP-dependent proteases, including single-chain FtsH and double-subunit Clp protease complexes ClpAP, ClpBP, ClpCP, and ClpXP, which were activated as the fever of infected mice in vivo. The expression of genes ftsH, clpA/B/C, and clpP, but not clpX, were significantly upregulated in S. suis in response to heat stress, while were not changed notably under the treatments with several other stresses, including oxidative, acidic, and cold stimulation. FtsH and ClpP were required for S. suis survival within host blood under heat stress in vitro and in vivo. Deletion of ftsH or clpP attenuated the tolerance of S. suis to heat, oxidative and acidic stresses, and significantly impaired the bacterial survival within macrophages. Further analysis identified that repressor CtsR directly binds and controls the clpA/B/C and clpP operons and is relieved by heat stress. In summary, the deployments of multiple ATP-dependent proteases form a flexible heat stress response network that appears to allow S. suis to fine-tune the degradation or refolding of the misfolded proteins to maintain cellular homeostasis and optimal survival during infection., (© 2024 Wiley‐VCH GmbH.)

The dorsal striatum is composed of the caudate nucleus and the putamen in human and non-human primates. These two regions receive different cortical projections and are functionally distinct. The caudate is involved in the control of goal-directed behaviors, while the putamen is implicated in habit learning and formation. Previous reports indicate that ethanol differentially influences neurotransmission in these two regions. Because neurotransmitters primarily signal through G protein-coupled receptors (GPCRs) to modulate neuronal activity, the present study aimed to determine whether ethanol had a region-dependent impact on the expression of proteins that are involved in the trafficking and function of GPCRs, including G protein subunits and their effectors, protein kinases, and elements of the cytoskeleton. Western blotting was performed to examine protein levels in the caudate and the putamen of male cynomolgus macaques that self-administered ethanol for 1 year under free access conditions, along with control animals that self-administered an isocaloric sweetened solution under identical operant conditions. Among the 18 proteins studied, we found that the levels of one protein (PKCβ) were increased, and 13 proteins (Gαi1/3, Gαi2, Gαo, Gβ1γ, PKCα, PKCε, CaMKII, GSK3β, β-actin, cofilin, α-tubulin, and tubulin polymerization promoting protein) were reduced in the caudate of alcohol-drinking macaques. However, ethanol did not alter the expression of any proteins examined in the putamen. These observations underscore the unique vulnerability of the caudate nucleus to changes in protein expression induced by chronic ethanol exposure. Whether these alterations are associated with ethanol-induced dysregulation of GPCR function and neurotransmission warrants future investigation., (© 2024 International Society for Neurochemistry.)

Background & Aims: Oxysterols have been implicated in biliary tract cancer (BTC), and Niemann-Pick C1-like 1 (NPC1L1) has been associated with oxysterol uptake in biliary and intestinal cells. Thus, our study aims to investigate the potential causal link between genetically proxied NPC1L1 inhibitors and the risk of BTC., Methods: In this study, we employed two genetic instruments as proxies for NPC1L1 inhibitors, which included LDL cholesterol-associated genetic variants located within or in close proximity to the NPC1L1 gene, as well as expression quantitative trait loci (eQTLs) of the NPC1L1 gene. Effect estimates were calculated using the Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) methods., Results: In MR analysis using the IVW method, both proxy instruments from the UK Biobank and the GLGC demonstrated a positive association between NPC1L1-mediated LDL cholesterol and BTC risk, with odds ratios (OR) of 10.30 (95% CI = 1.51-70.09; P = 0.017) and 5.61 (95% CI = 1.43-21.91; P = 0.013), respectively. Moreover, SMR analysis revealed a significant association between elevated NPC1L1 expression and increased BTC risk (OR = 1.19, 95% CI = 1.04-1.37; P = 0.014)., Conclusions: This MR study suggests a causal link between NPC1L1 inhibition and reduced BTC risk. NPC1L1 inhibitors, like ezetimibe, show potential for chemoprevention in precancerous BTC patients, requiring further clinical investigation., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aimed to identify the factors associated with insomnia in MRI-negative epilepsy and uncover the underlying pathological mechanism driving insomnia within the context of epilepsy., Methods: We conducted a retrospective study of patients with MRI-negative epilepsy recruited consecutively from December 2021 to December 2022. All subjects completed the Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Additionally, some subjects underwent the three-dimensional pseudo continuous arterial spin labeling(3D-pCASL) imaging examination. Bilateral frontal lobe, temporal lobe, hippocampus, thalamus, amygdala, caudate nucleus and lenticular nucleus were selected as regions of interest(ROI) and cerebral blood flow(CBF) values were measured in these regions. Subjects were classified into insomnia (ISI ≥ 10) or non-insomnia (ISI < 10) groups, and univariate and stepwise logistic regression analyses were employed to identify the factors associated with insomnia. Furthermore, CBF values in each ROI were compared between the two groups to identify the brain regions potentially related to the underlying pathological mechanism of insomnia in epilepsy., Results: A total of 73 patients with MRI-negative epilepsy were recruited in this study(men, 49.3 %). Among them, 14 patients(19.2 %) had insomnia. Univariate regression revealed that nocturnal seizures, number of anti-seizure medication(ASM), anxiety, use of valproic acid(VPA), depression, and excessive daytime sleepiness(EDS) may be associated with insomnia in MRI-negative epilepsy (all p＜0.05). Stepwise regression demonstrated that nocturnal seizures, anxiety, and EDS were independently associated with insomnia in MRI-negative epilepsy (OR[95 %CI]P: 14.64[2.02-106.27]0.008,49.35[3.06-796.61]0.006, 13.28[1.25-140.66]0.032, respectively). Furthermore, CBF values in the left amygdala were significantly lower in patients with MRI- negative epilepsy who had insomnia., Conclusion: The prevalence of insomnia in MRI-negative epilepsy is 19.2%. Nocturnal seizures, anxiety, and EDS were independently associated with insomnia in MRI-negative epilepsy. The noteworthy decrease in CBF values in the left amygdala might be connected to the underlying pathological mechanism of insomnia in epilepsy., 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 Inc. All rights reserved.)

The industrial applications of enzymes are usually hindered by the high production cost, intricate reusability, and low stability in terms of thermal, pH, salt, and storage. Therefore, the de novo design of nanozymes that possess the enzyme mimicking biocatalytic functions sheds new light on this field. Here, we propose a facile one-pot synthesis approach to construct Cu-chelated polydopamine nanozymes (PDA-Cu NPs) that can not only catalyze the chromogenic reaction of 2,4-dichlorophenol (2,4-DP) and 4-aminoantipyrine (4-AP), but also present enhanced photothermal catalytic degradation for typical textile dyes. Compared with natural laccase, the designed mimic has higher affinity to the substrate of 2,4-DP with K m of 0.13 mM. Interestingly, PDA-Cu nanoparticles are stable under extreme conditions (temperature, ionic strength, storage), are reusable for 6 cycles with 97 % activity, and exhibit superior substrate universality. Furthermore, PDA-Cu nanozymes show a remarkable acceleration of the catalytic degradation of dyes, malachite green (MG) and methylene blue (MB), under near-infrared (NIR) laser irradiation. These findings offer a promising paradigm on developing novel nanozymes for biomedicine, catalysis, and environmental engineering., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Junbai Li reports financial support was provided by National Natural Science Foundation of China. Yi Jia reports financial support was provided by National Natural Science Foundation of China. Yi Jia reports financial support was provided by National Key Research and Development Program of China]., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study investigated the effects of varying lipid ratios on the anaerobic co-digestion of high-lipid food waste (FW) in a mesophilic anaerobic membrane bioreactor (AnMBR). At a lipid concentration of 5 %, optimal biogas production (3.84 L/L/d) and lipid removal efficiency (78 %) were achieved; however, increasing lipid concentrations resulted in significant accumulations of long-chain fatty acids (LCFAs) and volatile fatty acids (VFAs). Batch tests further demonstrated the impact of various types of LCFAs, with stearic acid showing the slowest microbial growth rate (0.033d -1 ), confirming its role in the accumulation of acetate-dominated VFAs, potentially limiting the methanogenesis process at elevated lipid levels. Furthermore, at 8 % lipid content, the downregulation of key LCFA degradation enzymes and dominance of hydrogenotrophic methanogens indicated adverse conditions. The importance of the intricate interplay between LCFA degradation kinetics and microbial community for the system efficiency was evidenced, offering insights for optimizing and managing high-lipidic wastes., 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.)

Background:  There are few studies on continuous intercostal nerve block after single operation hole thoracoscopic surgery, that is, two-port thoracoscopic surgery., Objective:  To evaluate the analgesic effect of continuous intercostal nerve block after thoracoscopic surgery., Methods:  A total of 80 patients who underwent single operation hole thoracoscopic surgery in our hospital between September 2020 and June 2021 were enrolled and divided into two groups. Based on basic analgesia, an intercostal catheter was placed during the operation for continuous intercostal block analgesia after the operation in the experimental group (group A, n  = 40). The control group (group B, n  = 40) was treated with sufentanil intravenous analgesia after surgery, which is namely "basic analgesia." The postoperative pain scores, restlessness during the recovery period, effect on reducing opioid use, postoperative chest complications, patient satisfaction, etc., were compared between the two groups., Results:  The pain scores of patients in group A were significantly lower compared with those in group B at 12, 24, 36, and 48 hours after surgery (3.325 ± 1.163 vs. 4.550 ± 1.176, 2.650 ± 1.001 vs. 4.000 ± 1.038, 2.325 ± 0.917 vs. 3.700 ± 0.966, and 1.775 ± 1.050 vs. 3.150 ± 1.075, p  < 0.001, respectively). Sufentanil consumption in group A was significantly lower than in group B at 48 hours after surgery (98.625 ± 4.158 vs. 106.000 ± 7.228, p  < 0.001)., Conclusion:  Multimodal analgesia is ideal for early pain control after thoracotomy. A continuous intercostal nerve block can effectively reduce postoperative pain in patients., Competing Interests: None declared., (Thieme. All rights reserved.)

Optofluidics, which utilizes the interactions between light and fluids to realize various functions, has garnered increasing attention owing to the advantages of operational simplicity, exceptional flexibility, rapid response, etc. As one of the typical light-fluid interactions, the localized photothermal effect serving as a stimulus has been widely used for fluid manipulation. Particularly, significant progress on photothermal-driven droplet manipulation has been made. In this perspective, recent advancements in localized photothermal effect driven droplet manipulation are summarized. First, the photothermal manipulation of droplets on open surfaces is outlined. An attractive droplet manipulation of light droplet levitation above the gas-liquid interface via localized photothermal effect is then discussed. Besides, the photothermal-driven manipulation of droplets in an immiscible liquid phase is also discussed. Although promising, further development of photothermal-driven droplet manipulation is still needed. The challenges and perspectives of this light droplet manipulation strategy for broad implementation are summarized, which will help future studies and applications.

Neuronal activation is required for the formation of drug-associated memory, which is critical for the development, persistence, and relapse of drug addiction. Nevertheless, the metabolic mechanisms underlying energy production for neuronal activation remain poorly understood. In the study, a large-scale proteomics analysis of lysine crotonylation (Kcr), a type of protein posttranslational modification (PTM), reveals that cocaine promoted protein Kcr in the hippocampal dorsal dentate gyrus (dDG). We find that Kcr is predominantly discovered in a few enzymes critical for mitochondrial energy metabolism; in particular, pyruvate dehydrogenase (PDH) complex E1 subunit α (PDHA1) is crotonylated at the lysine 39 (K39) residue through P300 catalysis. Crotonylated PDHA1 promotes pyruvate metabolism by activating PDH to increase ATP production, thus providing energy for hippocampal neuronal activation and promoting cocaine-associated memory recall. Our findings identify Kcr of PDHA1 as a PTM that promotes pyruvate metabolism to enhance neuronal activity for cocaine-associated memory., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)