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Spinal cord injury (SCI) disrupts communication between the brain-derived descending commands and the intraspinal circuits, the central pattern generator (CPG), that execute movements. Dynamic changes in the interaction of the brain-spinal cord as well as in structure-function relationships play a vital role in the determination of neurological function restoration. These changes also have important clinical implications for the treatment of patients with SCI. After SCI, at both brain and spinal cord levels, detour circuits formation and neuronal plasticity have been linked to functional improvement under the condition of spontaneous recovery as well as electrical stimulation- and rehabilitative training-assisted recovery. The principles governing neural circuit remodeling and the neuronal subtypes specifically involved during the recovery from SCI are largely unknown. In the present review, we focus on how multi-level neural circuits are reconstructed after SCI. We highlight some new studies using rodent and zebrafish SCI models that describe how the intraspinal detour circuits are reconstructed and the important roles of spinal excitatory interneurons.

Summary: Background: Clinical appearance and high-frequency ultrasound (HFUS) are indispensable for diagnosing skin diseases by providing internal and external information. However, their complex combination brings challenges for primary care physicians and dermatologists. Thus, we developed a deep multimodal fusion network (DMFN) model combining analysis of clinical close-up and HFUS images for binary and multiclass classification in skin diseases. Methods: Between Jan 10, 2017, and Dec 31, 2020, the DMFN model was trained and validated using 1269 close-ups and 11,852 HFUS images from 1351 skin lesions. The monomodal convolutional neural network (CNN) model was trained and validated with the same close-up images for comparison. Subsequently, we did a prospective and multicenter study in China. Both CNN models were tested prospectively on 422 cases from 4 hospitals and compared with the results from human raters (general practitioners, general dermatologists, and dermatologists specialized in HFUS). The performance of binary classification (benign vs. malignant) and multiclass classification (the specific diagnoses of 17 types of skin diseases) measured by the area under the receiver operating characteristic curve (AUC) were evaluated. This study is registered with www.chictr.org.cn (ChiCTR2300074765). Findings: The performance of the DMFN model (AUC, 0.876) was superior to that of the monomodal CNN model (AUC, 0.697) in the binary classification (P = 0.0063), which was also better than that of the general practitioner (AUC, 0.651, P = 0.0025) and general dermatologists (AUC, 0.838; P = 0.0038). By integrating close-up and HFUS images, the DMFN model attained an almost identical performance in comparison to dermatologists (AUC, 0.876 vs. AUC, 0.891; P = 0.0080). For the multiclass classification, the DMFN model (AUC, 0.707) exhibited superior prediction performance compared with general dermatologists (AUC, 0.514; P = 0.0043) and dermatologists specialized in HFUS (AUC, 0.640; P = 0.0083), respectively. Compared to dermatologists specialized in HFUS, the DMFN model showed better or comparable performance in diagnosing 9 of the 17 skin diseases. Interpretation: The DMFN model combining analysis of clinical close-up and HFUS images exhibited satisfactory performance in the binary and multiclass classification compared with the dermatologists. It may be a valuable tool for general dermatologists and primary care providers. Funding: This work was supported in part by the National Natural Science Foundation of China and the Clinical research project of Shanghai Skin Disease Hospital.

Objective: Zishen Yutai Pill (ZYP) is a frequently used traditional Chinese medicine (TCM) preparation in women’s health. However, the effects of ZYP on endometrial epithelial response have not been fully explored. Herein, uterine natural killer cell (uNK) secretion medium was used to mimic the uterine microenvironment. Thereafter, an endometrial epithelial cell line (Ishikawa cells) was treated with ZYP-containing serum to elucidate the effects of ZYP on endometrial receptivity.Methods: uNK cells were isolated from decidual tissues of pregnant women undergoing pregnancy termination surgery, and thereafter, uNK secretion medium was collected. ZYP-containing serum was collected from rats after intragastrical administration of ZYP. Ishikawa cells were divided into three groups, one treated with blank control (control group), one treated with uNK secretion medium (uNK group), and one treated with both uNK secretion medium and ZYP-containing serum (ZYP + uNK group). Total RNAs were extracted. Gene expression profiles of Ishikawa in different groups were determined through microarray analysis. mRNA expressions of selected genes were determined through quantitative real-time polymerase chain reaction (qRT-PCR). Expression of intercellular cell adhesion molecule-1 (ICAM-1) was determined using Western blotting (WB). Results: Compared with the uNK group, the gene expressions of ZYP group with a total of 1117 genes were significantly altered, among which 510 genes were upregulated and 607 genes were downregulated. Compared with uNK group, expressions of CSF1, CSF2, SPP1, and ICAM1 were upregulated (P

Objective: Zishen Yutai Pill (ZYP), containing 15 Chinese traditional medicine, is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction. The current study was designed to investigate the therapeutic effects of ZYP on sperm quality and testis in varicocele (VC) rats. Materials and methods: Male Wistar rats were randomly divided into four groups (n = 6), i.e., a sham group, a VC group, and VC groups treated with different dose of ZYP (1575 and 3150 mg/kg/d, respectively). The experimental VC model was established by partial ligation of left renal vein. Six weeks after model establishment, ZYP was orally administered once a day for the next 6 weeks. Parameters relating to testis and sperm quality were assessed. Hematoxylin–eosin staining was used to showed testicular tissue damage in experimental VC rats. Expressions of proteins relating to NLRP3 inflammasome pathways were determined using Western blot (WB). The mRNA expressions of relating genes were determined using quantitative real-time PCR (qRT-PCR) analysis. Results: ZYP could significantly improve sperm motility and decrease sperm DNA fragmentation index in VC rats (P

Consumer interest in probiotics is significantly growing due to their positive impact on their health. Dairy products are common and most preferred probiotics ''delivery vehicle'' in the food industry. However, dairy products are associated with increased risk to people, with lactose intolerance, galactosemia, allergy to milk proteins, and high cholesterol levels. For such cases, non-dairy based probiotic foods could offer a good alternative. Among non-dairy foods, fruit juice is more dietary inclusive, convenient, and well accepted by all the age groups. Therefore, fruit juice could be used as a suitable non-dairy food carrier in probiotic delivery. Lactobacillus and Bifidobacterium are the two main strains used commercially worldwide for preparing probiotic products with proven health benefits. However, protecting the probiotic cells is the key for probiotic formulation in order to guarantee the survival. Therefore, various encapsulation techniques, cell viability, and suitable carrier materials in downstream processing and utilization are discussed in the review. Among different encapsulation techniques, spray drying emerged as an alternative technique for better utilization of probiotics in fruit juices with possibilities for industrial applications due to cost-effective and continuous process. Therefore, spray drying could be considered as an efficient encapsulation technique in food industry for fruit juice probiotification.

Adenovirus (Ad) is a non-enveloped linear double-stranded DNA virus with >50 serotypes in humans. Ad vectors have been used as gene delivery vehicles to express transgenes, small interfering RNAs (siRNAs) for gene silencing, or CRISPR/Cas and designer nucleases for genome editing. Although several methods are used to generate Ad vectors, the Ad-making process remains technically challenging and time consuming. Moreover, the Ad-making techniques have not been improved for the past two decades. Gibson DNA Assembly (GDA) technology allows one-step isothermal DNA assembly of multiple overlapping fragments. Here, we developed a one-step construction of Ad (OSCA) system using GDA technology. Specifically, we first engineered several adenoviral recipient vectors that contain the ccdB suicide gene flanked with two 20-bp unique sequences, which serve as universal sites for GDA reactions in the Ad genome ΔE1 region. In two proof-of-principle experiments, we demonstrated that the GDA reactions were highly efficient and that the resulting Ad plasmids could be effectively packaged into Ads. Ad-mediated expression of mouse BMP9 in mesenchymal stem cells was shown to effectively induce osteogenic differentiation both in vitro and in vivo. Collectively, our results demonstrate that the OSCA system drastically streamlines the Ad-making process and should facilitate Ad-based applications in basic, translational, and clinical research.

Finger joint motion monitoring is crucial for rehabilitation training and ergonomics. Based on a multilayer dielectric structure, this study proposed flexible and highly sensitive ionic skins (sensors) for the measurement of the bending angles of finger joints. Each ionic skin, consisting silicon rubber films (multiple dielectric layers) and highly stretchable ionic conductors, was attached to the finger joint surface. The capacitance change of the skin was captured and used to measure finger joint bending angles. On this basis, the relationship between angles and capacitance variations was established. The relationship agreed with the experimental results. Furthermore, the effect of number of dielectric layers on sensitivity and linearity was discussed. The experimental results indicated that an increase in the number of dielectric layers improved sensitivity but suppressed linearity. The proposed ionic skins provided higher sensitivity and linearity than other flexible sensors. The five-layer ionic skin was four times more sensitive than existing ionic skins. The results confirmed that the multilayer dielectric structure of our ionic skins substantially enhanced the sensitivity for finger joint bending angle measurements.

Cardiosphere-derived cell exosomes (CDCexo) and YF1, a CDCexo-derived non-coding RNA, elicit therapeutic bioactivity in models of myocardial infarction and hypertensive hypertrophy. Here we tested the hypothesis that YF1, a 56-nucleotide Y RNA fragment, could alleviate cardiomyocyte hypertrophy, inflammation, and fibrosis associated with hypertrophic cardiomyopathy (HCM) in transgenic mice harboring a clinically relevant mutation in cardiac troponin I (cTnIGly146). By quantitative PCR, YF1 was detectable in bone marrow, spleen, liver, and heart 30 min after intravenous (i.v.) infusion. For efficacy studies, mice were randomly allocated to receive i.v. YF1 or vehicle, monitored for ambulatory and cardiac function, and sacrificed at 4 weeks. YF1 (but not vehicle) improved ambulation and reduced cardiac hypertrophy and fibrosis. In parallel, peripheral mobilization of neutrophils and proinflammatory monocytes was decreased, and fewer macrophages infiltrated the heart. RNA-sequencing of macrophages revealed that YF1 confers substantive and broad changes in gene expression, modulating pathways associated with immunological disease and inflammatory responses. Together, these data demonstrate that YF1 can reverse hypertrophic and fibrotic signaling pathways associated with HCM, while improving function, raising the prospect that YF1 may be a viable novel therapeutic candidate for HCM.

RNA interference (RNAi) is mediated by an ∼21-nt double-stranded small interfering RNA (siRNA) and shows great promise in delineating gene functions and in developing therapeutics for human diseases. However, effective gene silencing usually requires the delivery of multiple siRNAs for a given gene, which is often technically challenging and time-consuming. In this study, by exploiting the type IIS restriction endonuclease-based synthetic biology methodology, we developed the fast assembly of multiplex siRNAs (FAMSi) system. In our proof-of-concept experiments, we demonstrated that multiple fragments containing three, four, or five siRNA sites targeting common Smad4 and/or BMPR-specific Smad1, Smad5, and Smad8 required for BMP9 signaling could be assembled efficiently. The constructed multiplex siRNAs effectively knocked down the expression of Smad4 and/or Smad1, Smad5, and Smad8 in mesenchymal stem cells (MSCs), and they inhibited all aspects of BMP9-induced osteogenic differentiation in bone marrow MSCs (BMSCs), including decreased expression of osteogenic regulators/markers, reduced osteogenic marker alkaline phosphatase (ALP) activity, and diminished in vitro matrix mineralization and in vivo ectopic bone formation. Collectively, we demonstrate that the engineered FAMSi system provides a fast-track platform for assembling multiplexed siRNAs in a single vector, and thus it may be a valuable tool to study gene functions or to develop novel siRNA-based therapeutics.

Background: Zishen Guchong Pill (ZGP), a traditional oriental herbal medicine, has been applied broadly in the treatment of threatened or recurrent miscarriages in clinics, but little is known about its developmental toxicity.Aim of the study: This study aimed to investigate the potential toxicity of ZGP and its mechanisms.methods: We investigated the developmental toxicity of ZGP using a zebrafish model. Zebrafish embryos at 4 hours post-fertilization (hpf) were exposed to 25, 50, 100, and 200 µg/mL ZGP until 120 hpf. The zebrafish morphology, organ development, reactive oxygen species (ROS) content, oxidative stress-related enzyme activity, and mRNA levels of oxidative stress and apoptosis-related genes were measured.Results: Our results demonstrated that ZGP had no toxicity at 50 µg/mL ZGP but induced phenotypic defects and decreased the hatching rate and body length at more than 50 µg/mL ZGP (high dose). High doses of ZGP caused severe heart failure, including a significant increase in the sinus venosus (SV) and bulbus arteriosus (BA) distance and pericardial area, and reduced heart rate and numbers of red blood cells. In addition, high doses of ZGP caused liver atrophy and decreased the length of dopamine ganglia and neurovascular. High doses of ZGP elicited the generation of ROS and elevated malondialdehyde levels, but reduced the activity of superoxide dismutase (SOD) and catalase (CAT). Real-time PCR data showed the downregulation of oxidative stress-related genes (sod and cat) and the activation of Nrf2 (nrf2, keap1, ho-1, nqo1, gclc, and gclm) and P53 (p53, bcl-2, and bax) signal pathway genes after high ZGP exposure.Conclusions: Taken together, our results indicate that ZGP has no developmental toxicity under 50 µg/mL ZGP but induced developmental toxicity in zebrafish embryos at more than 50 µg/mL ZGP, and oxidative stress contributed to the toxic response. • ZGP is safe and reliable in clinical use. • ZGP (high does) caused an increase in ROS, which induced oxidative stress, leading to apoptosis and developmental toxicity. • The Nrf2 signaling pathway is impaired during the early stages of ZGP-induced developmental toxicity.

Normal aging is accompanied by structural degeneration and glucose hypometabolism in the human brain. However, the relationship between structural network disconnections and hypometabolism in normal aging remains largely unknown. In the present study, by combining MRI and PET techniques, we investigated the metabolic mechanism of the structural brain connectome and its relationship with normal aging in a cross-sectional, community-based cohort of 42 cognitively normal elderly individuals aged 57–84 years. The structural connectome was constructed based on diffusion MRI tractography, and the network efficiency metrics were quantified using graph theory analyses. FDG-PET scanning was performed to evaluate the glucose metabolic level in the cortical regions of the individuals. The results of this study demonstrated that both network efficiency and cortical metabolism decrease with age (both p

Summary: Adhesive hydrogels containing catechol moieties have many important applications, but the fabrication of effective long-lasting adhesive hydrogels remains a challenge because of oxidative damage. Inspired by the traditional use of quercetin in ancient China, here, we have developed a novel method, based on quercetin-assisted photoradical chemistry, to fabricate a durable adhesive hydrogel, Q-hydrogel. In the presence of light, quercetin generates quinone/semiquinone radicals, which subsequently interact with ammonium persulfate (APS) to produce a large amount of free radicals and initiate polymerization of the hydrogel. As-prepared Q-hydrogel showed good mechanical and adhesive properties, which were attributed to the inherent structural advantages of quercetin. Because of the resistance of quercetin to oxidation, as-prepared Q-hydrogel also showed good adhesive properties even after treatment with oxidizing agents. Capitalizing on its conductivity and adhesive properties, Q-hydrogel was successfully used to produce wearable sensors capable of detecting human motion.

Male sterility induced by a chemical hybridization agent (CHA) is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male sterility. To investigate effects of different treatment times of CHA-SQ-1 used, morphological, biochemical and physiological responses of wheat flag leaves were detected in this study. CHA induced programmed cell death (PCD) as shown in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) and DNA laddering analysis. In the early phase, CHA-SQ-1 trig-gered organelle changes and PCD in wheat leaves accompanied by excess production of reactive oxygen species (O2 and H2O2) and down-regulation of the activities of superoxide dismutase (SOD), catalase (CAT) and guaiacol peroxidase (POD). Meanwhile, leaf cell DNAs showed ladder-like patterns on agarose gel, indicating that CHA-SQ-1 led to the activation of the responsible endonuclease. The oxidative stress assays showed that lipid peroxidation was strongly activated and photosynthesis was obviously inhibited in SQ-1-induced leaves. However, CHA contents in wheat leaves gradually reduced along with the time CHA-SQ-1 applied. Young flags returned to an oxidative/antioxidative balance and ultimately developed into mature green leaves. These results provide explanation of the relations between PCD and anther abortion and practical application of CHA for hybrid breeding.

To date, the molecular pathogenic mechanisms between HBsAg and liver metabolic disorders have not been fully understood. To explore the overall effects of HBsAg on liver tissues from HBV transgenic mice, proteome, interactome, and signal pathway analysis were employed to uncover the underlying mechanisms. Bioinformatics analysis of 191 differentially expressed proteins suggested that HBV upregulated the expression of multiple enzymes involved in lipid synthesis, and small HBs (SHBs) caused lipid accumulation in cells. Further studies showed that SHBs bound to binding immunoglobulin protein (Bip), which normally functions in cell homeostasis against the unfolded protein response (UPR) signaling via occupying inositol-requiring enzyme 1 (IRE1). Hijacking Bip by SHBs alleviated the inhibition of post-endoplasmic reticulum (ER) signaling and sequential activation of the IRE1 downstream transcription factors involved in lipid synthesis, such as spliced X-box binding protein 1 (sXBP1) and sterol regulatory element-binding protein 1 (SREBP1), leading to lipid metabolism disorder. The restoration of Bip can alleviate ER stress, and block the sequential post-ER signaling caused by SHBs. This study revealed a new pathway through which SHBs promote lipid disorder, and suggests that Bip may serve as a novel target for intervention in HBV related liver diseases. SIGNIFICANCE: In this study, we found a new pathway promoting the lipid disorder by SHBs through quantitative proteomics studies, and Bip may serve as a novel target for intervention in HBV related liver diseases. These findings highlight a novel role of SHBs in regulating cell lipid metabolism and provide an insight into the relationship between HBV infection and liver fatty disorders, which may serve as a potential therapeutic target for intervention of HBV related liver diseases., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Ischemia-reperfusion injury is a common cause of cardiovascular and cerebrovascular diseases. The reoxygenation during reperfusion leads to an overproduction of reactive oxygen species (ROS). As an antioxidant, H 2 S can scavenge ROS to inhibit oxidative stress and inflammatory reaction, thus attenuating ischemia-reperfusion injury. In this process, the changes of cellular microenvironment (polarity or viscosity) have not been fully discussed. In order to real-time track the changes of cellular microenvironment during the treatment of ischemia-reperfusion injury with H 2 S. It is necessary to develop highly selective and sensitive probes that can cascade response to hydrogen sulfide and cellular microenvironment., Results: We designed and synthesized a fluorescent probe TPEC-DNBS which can produce cascade response to H 2 S and microenvironment. An intermediate TPEC-OH is produced after highly selective and sensitive response to H 2 S, which can further respond to polarity and viscosity. In addition, due to the aggregation-induced emission (AIE) and twisted intramolecular charge transfer (TICT) effects, polarity can promote the fluorescence emission wavelength and intensity of TPEC-OH to produce double response characteristics, and its change trend (from weak green fluorescence at low polarity to strong red fluorescence at high polarity) is opposite to that of traditional polar probes (from strong green fluorescence at low polarity to weak red fluorescence at high polarity). Viscosity can only induce the change of fluorescence intensity. By constructing the cardiomyocyte model and hepatocyte model of ischemia-reperfusion, we further prove that after ischemia-reperfusion injury, the cells are in an environment of low polarity, and the microenvironment can be recovered after H 2 S treatment., Significance: An AIE-TICT fluorescence probe capable of cascading responses to H 2 S, polarity and viscosity was constructed by using tetraphenylethylene and coumarin moieties. This probe provides a more intuitive and convenient condition for real-time tracking the changes of cellular microenvironment (polarity or viscosity) before and after H 2 S treatment of ischemia-reperfusion injury., 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.)

A novel extra-long carbon-chain salamo-like fluorescent chemical probe DNS (named as 2,2'-[1,10-(decanedioxy)bis(nitromethyldyne)]dinaphthol) containing ten methylene groups was synthesized based on the 2-hydroxy-1-naphthylaldehyde unit. Research has shown that the fluorescent probe DNS can achieve efficient and selective recognition of CO 3 2- anions, with a detection limit LOD=1.59 × 10 -8 M. The binding constant Ka = 3.7 × 10 4 M -1 and quantification limit is as low as LOQ=4.31 × 10 -8 M, respectively. The possible identification mechanism of the fluorescent chemosensor DNS was analyzed and studied through fluorescence titration and nuclear magnetic titration. The results showed that the fluorescence chemical sensor DNS is deprotonated by CO 3 2- anions, enhancing its fluorescence and producing a ICT effect., 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.)

Research on high-molecular-weight polysaccharides tends to be more difficult and lag in terms of their fine structures and bioavailability. We focused on Gastrodia elata Blume polysaccharides (GEPs) with different molecular weights and structural characteristics to reveal their bioactivities, especially those abundant high-molecular-weight GEPs. A novel high-yield polysaccharide (GEP1-2) with the high molecular weight of 3.21 × 10 6  Da was first purified. Through conventional and enzymolysis-assisted analyses, GEP1-2 was an α-D-(1,4)(1,6)-glucan with unique linkages of →2)-β-D-Frucf-(1→, →4)-β-D-Glcp-(1→ and p-hydroxybenzyl alcohol citrate (HAC), and its main local fine structure had α-1-Glcp, α-1,4-Glcp, α-1,6-Glcp, β-1,6-Galp, and α-1,4,6-Glcp at the molar ratio of 1.20∶17.74∶2.71∶0.98∶0.76. Another refined GEP3-3 with 1.91 × 10 4  Da was identified as an α-1,4- and α-1,4,6-glucan (molar ratio of 4.91∶1.02). It was noteworthy that all GEPs could induce the release and mRNA expressions of NO and cytokines in RAW264.7 macrophages. Specially, the high-molecular-weight polysaccharides showed comparable in vitro immune-enhancing effects to the low-molecular-weight polysaccharide. Furthermore, the macromolecular GEP1-2 could dose-dependently increase the organ coefficient of thymus and cytokine levels of TNF-α and IL-6 in mouse serum as well as in splenic lymphocytes. These efforts will be of great significance when proceeding to the safe relief or therapy of macromolecular GEPs for immunologic diseases., 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 © 2025. Published by Elsevier B.V.)

Background: Cachexia is associated with multiple adverse outcomes in cancer. However, clinical decision-making for oncology patients at the cachexia stage presents significant challenges., Objective: This study aims to develop a machine learning (ML) model to identify potentially reversible cancer cachexia (PRCC)., Methods: This was a multicenter cohort study. Cachexia was retrospectively diagnosed using Fearon's framework. PRCC was defined as a diagnosis of cancer cachexia at baseline that turned negative one month later. Body weight dynamics accessible upon patient admission were screened and modeled to predict PRCC. Multiple ML models were trained and cross-validated using 70% of the data to predict PRCC, with the remaining 30% reserved for model evaluation. The interpretability and clinical usefulness of the optimal model were assessed, and external validation was performed in an independent cohort of 238 patients., Results: The study enrolled 1983 men and 1784 women (median age=58 years). PRCC was identified in 1983 patients (52.6%). Breast cancer exhibited the highest rate of PRCC (72.1%), while cachexia associated with various gastrointestinal cancers was less likely to be reversed. Weight change (WC) from six months ago to one month ago, WC from one month ago to baseline (-1 to 0) and baseline body mass index were selected for modelling. A multilayer perceptron model showed good performance to predict PRCC in the holdout test set (AUC [95%CI] = 0.887 [0.866, 0.907], accuracy=0.836, sensitivity=0.859, specificity=0.812) and the external validation set (AUC [95%CI] = 0.863 [0.778, 0.948]). The WC -1 to 0 showed the highest impact on model output. The model was demonstrated to be clinically useful and statistically relevant., Conclusions: This study presents an explainable ML model for the early identification of PRCC that utilizes simple body weight dynamics. The findings showcase the potential of this approach in improving the management of cancer cachexia to optimize patient outcomes., Registration Information: Data described in the manuscript was derived from a registered research project (URL: http://www.chictr.org.cn/showproj.aspx?proj=31813; ID: ChiCTR1800020329)., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Liangyu Yin reports financial support was provided by National Natural Science Foundation of China. Hongxia Xu reports financial support was provided by Natural Science Foundation Project of Chongqing. Hanping Shi reports financial support was provided by National Key Research and Development Program of China. 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 © 2025 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Aging is a critical biological process, with particularly notable impacts on the kidneys. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of transferring various bioactive molecules, which exhibit beneficial therapeutic effects on kidney diseases. This study demonstrates that exosomes derived from hUC-MSCs ameliorate cellular senescence in the kidneys of naturally aging mice. These exosomes reduce the protein expression of senescence markers and senescence-associated secretory phenotypes (SASP) leading to fewer DNA damage foci and increased expression of the proliferation indicator Ki67. During the aging process, many proteins undergo phosphorylation modifications. We utilized data-independent acquisition (DIA) phosphoproteomics to study kidneys of naturally aging mice and those treated with hUC-MSC-derived exosomes. We observed elevated phosphorylation levels of the differentially phosphorylated proteins, Lamin A/C, at Ser390 and Ser392 sites, which were subsequently verified by western blotting. Overall, this study provides a new molecular characterization of hUC-MSC-derived exosomes in mitigating cellular senescence in the kidneys. SIGNIFICANCE: DIA phosphoproteomics was employed to investigate phosphorylated proteins in the kidney tissues of naturally aging mice with hUCMSC-exos treated. The results demonstrated that the DIA technique detected a higher abundance of phosphorylated proteins. We identified 24 significantly differentially phosphorylated proteins, and found that the phosphorylation of specific Lamin A/C sites is crucial for preventing cellular senescence. This study will help to better reveal the related phosphorylated proteins involved in hUCMSC-exos intervention in the kidneys of naturally aging mice, providing a foundation for future research on specific phosphorylation sites of proteins as potential therapeutic targets for renal aging-related diseases., 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.)

Seabuckthorn (Hippophae rhamnoides) is an excellent plant that has the concomitant function of both medicine and foodstuff with high nutritional and health-promoting properties. As a pivotal bioactive component mainly existing in the seeds and leaves, seabuckthorn protein and its derived peptides have aroused wide attention owing to their multifaceted pharmacological activities, including anti-hypertensive, hypoglycemic, anti-obesity, anti-freeze, immunomodulatory, anti-inflammatory, sobriety, anti-oxidant and anti-neurodegenerative functions. Despite these promising attributes, the application of seabuckthorn peptides as functional food and medicines are impeded due to lack of a comprehensive understanding of pharmacological activities and intricate structure-activity relationship. Therefore, this review systematically summarizes the latest advancements in the extraction, purification, structural characteristics, pharmacological activities, digestion, absorption and transport, and application of seabuckthorn protein or peptides. Noteworthily, the structure-activity relationship is specifically delved into the hypoglycemic, anti-hypertensive, anti-obesity, anti-neurodegenerative and anti-oxidant peptides. Moreover, the shortcomings of current research and promising prospects are also highlighted. This comprehensive overview will provide a framework for future exploration and application of seabuckthorn protein or peptides in the realms of food and pharmaceuticals, offering a promising horizon for health benefits., Competing Interests: Declaration of competing interest The authors declare that there exist no discernible financial conflicts of interest or personal relationships that might have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The impact of micro/nano plastics (MPs/NPs) on human health is a significant area of research. Studies on the effects of maternal exposure to microplastics (MPs) on the fertility in offspring have been conducted, but the damage caused by nanoplastics (NPs) remains ambiguous. In this study, pregnant Kunming mice were exposed to 30 mg/kg/day PS-NPs from 0.5 gestation day (GD) to 21 days postpartum (dpp). Increased rates of miscarriage and premature delivery were observed, as well as reduced litter size, indicating potential permanent reproductive injury in mice of PS-NPs group. Maternal exposure to PS-NPs impaired fertility of the female offsprings. Decreased primordial and increased growing follicles were observed in the ovaries of offspring at 1 dpp and 7 dpp in PS-NPs group, indicating premature activation of primordial follicles. This premature activation is likely due to the PS-NPs'induction of the AKT-FOXO3a signaling pathway by downregulating AMPK phosphorylation level and enhancing mTOR activity. Furthermore, a significant reduction in transzonal projections (TZPs) was noted in the ovaries of adult offspring mice in PS-NPs group. RNA sequencing of the ovaries from adult offspring female mice revealed that the TZPs related genes may be linked to CAMKIIβ, with a corresponding downregulation in expression levels. Overall, maternal exposure to PS-NPs induced profound and enduring effects on the reproductive functions of female offspring, raising critical alarms regarding the multigenerational reproductive toxicity risks associated with nanoplastic exposure in mammals., 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 © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

The hydrodynamics, water temperature, and water quality model for the Dan River and Renzhuang Reservoir continuum were developed using field monitoring data and the Environmental Fluid Dynamics Code (EFDC). An in-situ water discharge experiment enabled the calculation of water propagation time using a simulated flood progression method and the hydrodynamics module of EFDC. Based on these model results, degradation coefficients for chemical oxygen demand, biochemical oxygen demand, nitrogen (N), phosphorus (P), fluoride, arsenic were determined, revealing significantly higher values when the wetland barrage was opening. According to field monitoring and EFDC model outputs, the water environment capacity (WEC) of total nitrogen (TN) in Dan River was even negative, with the WEC of TN and total phosphorus (TP) in Renzhuang Reservoir being very low at 147 kg/d and 1490 kg/d, respective. Furthermore, the water environment carrying capacity (WECC) was found to be extremely low (~0.2 %) and limited by TN and TP. The results demonstrated that the spatiotemporal variations of water quality presented by the EFDC model facilitate an intuitive and comprehensive observation of water quality compliance rates over time and space, providing valuable references for decision-makers. The WEC and WECC of the study area underscored the urgency of N and P coordination control., 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.)

Avian pathogen Escherichia coli (APEC) poses a significant threat to poultry farming, causing colibacillosis in various hosts, including chickens, ducks, geese, and pigeons. This study aimed to investigate the molecular epidemiology of APEC in Jiangxi Province, China, to inform prevention and control strategies. Between 2020 and 2024, 186 APEC strains were isolated and identified, with 88.7 % from liver samples and 5.4 % from brain tissues. Whole-genome sequencing and analysis revealed that serotypes O145, O78, O8, and O111 comprised 32.9 %, 9.3 %, 7.9 %, and 4.3 % of the isolates, respectively. The dominant H serotypes included H21 (23.8 %), H9 (22.7 %), and H4 (18.2 %), with ST23 being the most prevalent sequence type at 24.2 %, followed by ST117 (10.1 %) and ST2505 (7.3 %). Virulence-associated genes in the strains O145, O78, O8, and O111 were further analyzed for quantity and pattern. Eight strains were selected for in vivo pathogenicity testing in ducks, four highly pathogenic strains were then identified, which were used to develop inactivated vaccines with the novel aqueous adjuvant MONTANIDE™ GEL P PR and the traditional adjuvant alumVax hydroxide. Compared with existing vaccines, those formulated in this study showed superior protection, with the MONTANIDE™ GEL P PR adjuvant achieving the highest protection rate (90.0 %, 36/40) and lower lesion scores. This research enhances the understanding of APEC epidemiology and offers promising strategies for effective vaccine development against prevalent APEC., Competing Interests: Declaration of 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 the present paper., (Copyright © 2025. Published by Elsevier Inc.)

Seven diterpenoids including five ent-cleistanthanes (1, 2, 4-6) and two ent-pimaranes (3, 7) were isolated for the first time from the aerial part of Phyllanthus franchetianus H. Lév. Their structures were elucidated on the basis of the extensive spectroscopic analyses, single-crystal X-ray diffraction and ECD analysis. Phyllanthanes A-C (1-3) are new compounds. Notably, the ent-cleistanthanes 1 and 4-5 exhibited moderate cytotoxicity against five human cancer (HL-60, A549, HepG2, MDA-MB-231, SW480) (IC 50  = 5.01-32.41 μM) and one normal BEAS-2B (IC 50  = 20.45-24.33 μM) cell lines., Competing Interests: Declaration of competing interest The authors of the present manuscript have declared that no competing interests exist., (Copyright © 2024 Elsevier B.V. All rights reserved.)

β-Carboline alkaloids are a broad class of indole alkaloids that were first isolated from Peganum harmala L., a traditional Chinese herbal remedy. β-Carboline alkaloids have been found to have many pharmacological activities, including anti-inflammatory, antioxidant, and anti-cancer properties. β-Carboline alkaloids have been studied, and nine therapeutic medications based on its structural skeleton have been utilized to treat a range of illnesses. These compounds' potent pharmacological action and high druggability have garnered a lot of interest. This review systematically summarized resource distribution, pharmacological activity, toxicology and clinical drugs of β-Carboline alkaloids. These alkaloids are mostly found in plants, particularly (Peganum harmala L.), although they are also present in food, bacteria, fungus, and animals. By inhibiting NF-κB, MAPKs, and PI3K-AKT multiple signal pathways, they demonstrate a wide range of pharmacological activities, including anti-inflammatory, oxidative, neurological, cancer, fungal, and leishmania pharmacological activity. Toxicology revealed that β-Carboline alkaloids can produce confusion, irritability, dyskinesia, nausea, vomiting, and audiovisual hallucinations in addition to stimulating the central nervous system and inhibiting metabolism. Clinical drugs based on β-Carboline alkaloids have been used for clinical treatment of arrhythmia, cerebrovascular diseases and dysfunction, hypertension, epilepsy, malaria and mydriasis diseases. It will prompt us to redefine β-Carboline alkaloids. For β-Carboline alkaloids that inspires pharmacological applications in medicine and the development of novel medications containing these alkaloids, it will be a useful resource., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024. Published by Elsevier B.V.)

Predicting the bioconcentration of chemical compounds plays a crucial role in assessing environmental risks and toxicological impacts. This study presents a robust multitask deep learning model for predicting the bioconcentration potential. The model can predict the bioconcentration of compounds in multiple categories, including non-bioconcentrative (non-BC), weakly bioconcentrative (weak-BC), and strongly bioconcentrative (strong-BC). We also employed the SHapley Additive exPlanations (SHAP) technology for the model interpretation. The binary classification models (non-BC vs BC and weak-BC vs strong-BC) showed good predictive performance, which achieved accuracy values over 90% and area under the curve (AUC) values with 0.95. The final ternary classification model provided an overall accuracy with 91.11%. Comparative analysis of molecular physicochemical properties showed that the importance of molecular weight, polar surface area, solubility, and hydrogen bonding are important for chemical bioconcentration. Besides, we identified eight structural alerts responsible for chemical bioconcentration. We made the model available as an online tool named BCdpi-predictor, which is accessible at http://bcdpi.sapredictor.cn/. Users can predict the bioconcentration potential of chemical compounds freely. The model has significant implications for environmental policy and regulatory frameworks, such as REACH, by providing a more accurate and interpretable method for assessing chemical risks. We hope that the results of this study can provide helpful tools and meaningful information for chemical bioconcentration prediction in environmental risk assessment., 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 rational design of nanozymes with highly efficient reactive oxygen species (ROS) generation to overcome the resistant infection microenvironment still faces a significant challenge. Herein, the highly active Fe single-atom nanozymes (Fe SAzymes) with a hierarchically porous nanostructure were prepared through a colloidal silica-induced template method. The proposed Fe SAzymes with satisfactory oxidase (OD)-like and peroxidase (POD)-like activity can transform O 2 and H 2 O 2 to superoxide anion free radical (•O 2 - ) and hydroxyl radical (•OH), which possess an excellent bactericidal effect. Also, the glutathione peroxidase (GPX)-like activity of Fe SAzymes can consume glutathione in the infection microenvironment, thus facilitating ROS generation to enhance the sterilization effect. Besides, the intrinsic photothermal effect of Fe SAzymes further significantly boosts the enzyme-like activity to generate much more reactive oxygen species for efficient antibacterial therapy. Accordingly, both in vitro and in vivo results indicate that the Fe SAzymes with synergistically photothermal-catalytic performances exhibit satisfactory antibacterial effects and biocompatibility. This work provides new insights into designing highly efficient SAzymes for effective sterilization applications by an amount of ROS generation., Competing Interests: Declaration of Competing Interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Parrotia subaequalis, an endangered Tertiary relict tree native to China and a member of the Hamamelidaceae family, is one of several host plant species in this family that exhibit unique ecological habits, such as gall formation. Tree galls are the results of complex interactions between gall-inducing insects and their host plant organs. The formation of galls may serve to protect other regions of the plant from potential damage, often through the production of phytoalexins. In this study, a preliminary investigation was carried out on the metabolites of the 90% MeOH extract derived from the closed spherical galls on the twigs of P. subaequalis. Consequently, nine previously undescribed benzofuran-type and dibenzofuran-type phytoalexins (parrotiagallols A-I, 1-9, respectively) were isolated and characterized, along with several known miscellaneous metabolites (10-17). Their chemical structures and absolute configurations were elucidated using spectroscopic methods, a combination of calculated and experimental electronic circular dichroism data, and single crystal X-ray diffraction analyses. Among these compounds, 1 and 2 are identified as neolignan derivatives, while compounds 3-5 are classified as 9,10-dinorneolignans. Compound 6 represents a rare 2,3-seco-neolignan, and compounds 7-9 are dihydroxy-dimethyl-dibenzofuran derivatives. Parrotiagallol A (1) showed considerable antibacterial activity against Staphylococcus aureus, with an MIC value of 14 μM. Additionally, parrotiagallol E (5) and methyl gallate (17) exhibited inhibitory effects against ATP-citrate lyase (ACL), a potential therapeutic target for hyperlipidemia, with IC 50 values of 5.1 and 9.8 μM, respectively. The findings underscore that galls not only serve as physical defense barriers but also benefit from the chemical defense system of the host plants. These insights provide avenues for exploring potential new therapeutic agents for S. aureus infections and ACL-related diseases, while also promoting scientific conservation strategies for P. subaequalis., 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.)

This special edition of the Journal of Pharmaceutical Sciences is dedicated to Professor Lynne S. Taylor (Retter Distinguished Professor of Pharmacy, Department of Industrial and Molecular Pharmaceutics, Purdue University), to honor her distinguished career as a pharmaceutical scientist and educator. The goal of this commentary is to provide an overview of Professor Taylor's career path, summarize her key research contributions, and provide some insight into her personal and professional contributions as an educator, mentor, wife, mother, friend, and adventurer., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to assess the relationship between socioeconomic status (SES) and chronic stress on the incidence of atrial fibrillation (AF) in older adults, and the potential role of chronic stress in the association., Methods: This study included 122,494 UK Biobank participants aged ≥60 years without AF at baseline. Latent class analysis was used to define the SES of participants. Chronic stress was measured using allostatic load (AL), and participants were categorized into low, medium and high AL groups. The Cox proportional hazards model, mediation, and interaction analyses were conducted to investigate the associations between SES, AL, and AF risk., Results: Low SES (hazard ratio [HR]: 1.10; 95 % confidence interval [CI]: 1.04-1.15) and high AL (HR: 1.37; 95 % CI: 1.30-1.45) were associated with an increased risk of AF, respectively. Individuals in the low SES and high AL groups exhibited the highest risk of AF compared to those in the high SES and low AL groups (HR: 1.46; 95 % CI: 1.32-1.61). We identified additive and multiplicative interactions in the low SES and high AL groups (relative risk due to interaction: 0.12 (95 % CI: 0.02-0.22); P for interaction = 0.0385). AL also exerted a partial mediating effect on the association between SES and the incidence of AF (mediation proportion: 17.3 %; 95 % CI: 5.9-28.7 %)., Conclusions: Our study revealed significant associations between SES, chronic stress, and the incidence of AF in older adults. Chronic stress was also shown to partially mediate the association., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Impaired decidualization is a major cause of infertility in patients with adenomyosis (AM). However, the effect of transcription factor 21 (TCF21) on AM and the underlying mechanism of associated-impaired decidualization remain unclear. The aim of this study was to investigate the expression of TCF21 in endometrial tissues of AM patients and the specific mechanisms by which it impairs the decidualization of human endometrial stromal cells (HESCs), with a view to improving the reproductive outcome of AM infertile patients., Methods: We compared gene expressions via transcriptomics between the control and AM-associated recurrent implantation failure (RIF) groups. qRT-PCR, western blot, and IHC were performed to confirm the expression and location of TCF21 in the endometrium. Furthermore, we confirmed that high expression of TCF21 impairs decidualization by qRT-PCR, immunofluorescence, and western blot. RNA-seq following overexpression of TCF21 in HESCs was conducted to identify TCF21-related molecular changes during in vitro decidualization. Then we performed ChIP-seq/qPCR and dual-luciferase reporter assay to explore the exact interaction between TCF21 and PDE4C. The related downstream mechanisms were further proved using IHC, qRT-PCR, western blot, and ELISA., Results: According to the RNA-seq analysis, TCF21 expression was remarkably higher in the endometrium of the AM-related RIF group compared to the control group. We confirmed the same results using samples from patients with AM and controls. TCF21 overexpression in HESCs impaired decidualization through suppression of decidual markers and cytoskeleton alterations. The mechanistic analysis revealed that TCF21 inhibited intracellular cAMP levels by directly increasing PDE4C expression and suppressing FOXO1 expression., Conclusions: TCF21 compromises decidualization in patients with AM via the PDE4C/cAMP-FOXO1 axis, which offers valuable insights on the pathology of decidualization-related infertility and indicates a potential treatment to improve endometrial receptivity in AM., Competing Interests: Declaration of competing interest Authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The skin is the immune system's first line of defense. Extensive skin burns can lead to tissue necrosis, sepsis, and even death. Anti-infectious care of burn wounds is a major challenge in clinical medicine. However, the extensive use of antibiotics led to the emergence of multi-drug-resistant bacteria and silver dressings with antibacterial effects are also cytotoxic. We used the natural cationic antibacterial agent ε-polylysine (EPL) to graft Epigallocatechin-3-gallate (EGCG) to synthesize EPL-EGCG. Then, we used methacrylated gelatin (GelMA) with arginine-glycine-aspartate-rich acid (RGD) sequence and EPL-EGCG form interpenetrating polymer network hydrogels with excellent swelling properties. The hydrogel's inherent antibacterial properties and photo-cross-linking properties can cover irregular burn wounds and isolate bacteria to prevent infection. In addition, we used polydopamine (PDA) to coat GelMA microspheres with excellent hemostatic efficacy and load platelet-rich plasma (PRP) to enhance the hemostatic efficacy of the microspheres and impart inflammation-regulating functions. The hydrogel showed excellent hemostatic efficacy in rat liver injury and tail vein injury models. In the rat infected burn model, the hydrogel exhibited favorable antimicrobial, pro-angiogenic, and anti-inflammatory phenotype polarization of macrophages. Our study shows that GelMA/EPL-EGCG/GM-PDA@PRP hydrogel application has excellent antibacterial, hemostatic and anti-inflammatory effects, providing a new treatment strategy for wound care before burn skin grafting., 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 B.V.)

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) is prone to complicated cardiovascular disease, and we aimed to identify patients with NAFLD who are prone to developing stable coronary artery disease (CAD)., Methods and Results: We retrospectively recruited adults who underwent coronary computed tomography angiography (CTA). A total of 127 NAFLD patients and 127 non-NAFLD patients were included in this study. Clinical features and imaging parameters were analysed, mainly including pericardial adipose tissue (PAT), pericoronary adipose tissue (PCAT), and radiomic features of 6792 PCATs. The inflammatory associations of NAFLD patients with PAT and PCAT were analysed. Clinical features (model 1), CTA parameters (model 2), the radscore (model 3), and a composite model (model 4) were constructed to identify patients with NAFLD with stable CAD. The presence of NAFLD resulted in a greater inflammatory involvement in all three coronary arteries (all P < 0.01) and was associated with increased PAT volume (r = 0.178**, P < 0.05). In the presence of NAFLD, the mean CT value of the PAT was significantly correlated with the fat attenuation index (FAI) in all three vessels and had the strongest correlation with the RCA FAI (r = 0.55, p < 0.001). A total of 9 radiomic features were screened by LASSO regression to calculate radiomic scores. In the model comparison, model 4 had the best performance of all models (AUC 0.914 [0.863-0.965]) and the highest overall diagnostic value of the model (sensitivity: 0.814, specificity: 0.941)., Conclusions: NAFLD correlates with PAT volume and PCAT inflammation. Furthermore, combining clinical features, CTA parameters, and radiomic scores can improve the efficiency of early diagnosis of stable CAD in patients with NAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

The purpose of this study was twofold: to identify the growth mechanisms of amorphous nanoparticles in solution and during the drying process at high temperatures, and to guide the process condition and stabilizer selection for amorphous nanoparticle formulations. In contrast to nanocrystals that are mostly mechanically robust, amorphous nanoparticles tend to undergo deformation under stress. As a result, development of a stable formulation and evaluation of the drying process for re-dispersible amorphous nanoparticles present considerable challenges. Although amorphous nanoparticles have stability issues, they have several pros in terms of production, high monodispersity, and diverse applications in drug delivery. In this study, amorphous nanoparticles were prepared via liquid-liquid phase separation, and their growth mechanisms were investigated both in solution and during the drying process. In solution, particles were found to be susceptible to flocculation, crystallization, coalescence, and Ostwald ripening, with coalescence being a preliminary step providing the driving force for Ostwald ripening. However, during the heat drying process, coalescence and crystallization were found to be the primary mechanisms for particle growth, with Ostwald ripening being negligible due to reduced molecular mobility. The glass transition temperature (T g ) of these amorphous nanoparticles was found to be a crucial factor both in solution and during the drying process. At temperatures < T g , particles remained in a rigid, glassy state thereby inhibiting coalescence, whereas at or above T g , particles transition from glassy to rubbery state, making them more susceptible to deformation and coalescence. The mechanistic understanding of particle growth from this study can also be extended to the stabilization of other types of soft nanoparticles., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Na Li reports financial support was provided by Dane O. Kildsig Center of Pharmaceutical Processing Research. Na Li reports financial support was provided by International Pharmaceuticals Excipients Council of the Americas. Paroma Chakravarty reports a relationship with Genentech Inc that includes: employment. 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 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Fenton reactions, commonly employed in environmental remediation, decompose H₂O₂ using Fe 2 ⁺ to generate free radicals. However, the efficiency is often limited by the slow conversion of Fe³⁺ to Fe 2 ⁺. In this study, we synthesize zero-valent iron nanoparticles (nZVI) via a green, plant extract-mediated reduction method, resulting in nZVI coated with a reductive polyphenolic layer that enhances Fe³⁺/Fe 2 ⁺ cycling. Supported on bamboo-derived biochar (BBC) via in situ reduction, the nZVI showe improved dispersibility and recovery during catalytic processes. Characterizations by SEM, TEM, FTIR, XRD, and XPS together confirm the successful synthesis of the nZVI/BBC composite. We evaluate the catalytic performance by degrading Eriochrome Black T (EBT) dye in the presence of H₂O₂. Under optimal conditions (35 °C, pH 3), the nZVI/BBC catalyst achieves over 90% degradation of EBT within 10 min. The dual function of the surface-functionalized nZVI as both iron source and co-catalyst significantly improves the reaction efficiency, offering a promising approach for environmental remediation., 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.)

c-Src, also known as cellular Src, is a non-receptor tyrosine kinase that plays a crucial role in various cellular processes, including cell proliferation, adhesion, and migration. Its dysregulation has been implicated in the development and progression of several diseases, particularly cancer. Current therapeutic agents targeting c-Src are primarily small molecules binding to its kinase domain. However, drug resistance often reduces the effectiveness of these drugs. The SH3 domain of c-Src is a highly conserved functional region with a low propensity for developing drug resistance, whereas there are no existing anti-cancer drugs specifically binding to this domain. In this study, structure-based virtual screening and thermal shift experimental verification identified three molecules that showed potent binding affinity with SH3 domain of c-Src. Subsequent kinase activity assay validated the inhibitory activity of these compounds against c-Src, with IC 50 values ranging from 60.42 to 122.2 nM. Next, cell-level assays and preliminary study were conducted to further evaluate the efficacy of the identified active compounds. In conclusion, the present work has provided new chemical templates as lead structures for the future development of new antitumor therapeutics targeting the c-Src SH3 domain to overcome drug resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Microwave-assisted enzymatic hydrolysis is an effective method to shorten the preparation time of porous starch. This study aims to investigate the effect of microwave treatment before/during/after enzymatic hydrolysis on the properties of porous starch. The results showed that the physicochemical properties of the porous starch obtained by microwave-assisted enzymatic hydrolysis were improved. All the samples were typical A-type crystal shapes, and the basic internal structures were the same. Among the samples, the porous starch obtained by microwave treatment during enzymatic hydrolysis (MDEPS) had the largest pore area, the highest number of pores, and significantly improved adsorption capacity, with oil and water absorption rates increased from 84.32 % to 103.1 % and 115 % to 170 % (P < 0.05), respectively. These results demonstrated that microwave treatment during enzymatic hydrolysis has great potential as a green and efficient method for preparing porous starch., 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 © 2025 Elsevier B.V. All rights reserved.)

Ferritin-based hybrids are large 24-subunit macromolecules of megadalton scale have prospective applications ranging from drug delivery to recombinant vaccines, however, their rational design is challenging. Here, we architectured hybrids based on ferritin subunits from Helicobacter pylori and ones fused with a homolog of the Small Ubiquitin-like Modifier protein. We firstly revealed the stochastic nature of bacterial ferritin-based hybrids self-assembly by observing a sequential range of stoichiometries at totally different sample preparation procedures: coexpression in Escherichia coli cells and pH-dependent dis/reassembly. We developed an approach of quantitative evaluation of stoichiometry distribution by using a model based on random, unambiguous, and stoichiometry-independent assembly of hexamers into 24-meric hybrid globules. We identified the presence of a heterodimer and found unexpectedly disfavored stoichiometries of hexamers, which determined the narrowing of structural diversity patterns of 24-mers and shifted the stoichiometry distribution from the random one. Our findings provide new insights into the molecular mechanisms governing the shift in structural diversity patterns of ferritin-based hybrid globules. Finally, the combination of our model system and the hexamer-based approach provides a robust platform for the rational design of ferritin-based systems, with potential applications in drug delivery, structure-based immunogen design, and beyond., 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 B.V.)

Syringaresinol, a phytochemical constituent belonging to lignan, is formed from two sinapyl alcohol units linked via a β-β linkage, which can be found in a wide variety of cereals and medicinal plants. Medical researches revealed that Syringaresinol possesses a broad spectrum of biological activities, including anti-inflammatory, anti-oxidation, anticancer, antibacterial, antiviral, neuroprotection, and vasodilation effects. These pharmacological properties lay the foundation for its use in treating various diseases such as inflammatory diseases, neurodegenerative disorders, diabetes and its complication, skin disorders, cancer, cardiovascular, and cerebrovascular diseases. As the demand for natural therapeutics increases, Syringaresinol has garnered significant attention for its pharmacological properties. Despite the extensive literature that highlights the various biological activities of this molecule, the underlying mechanisms and the interrelationships between these activities are rarely addressed from a comprehensive perspective. Moreover, no thorough comprehensive summary and evaluation of Syringaresinol has been conducted to offer recommendations for potential future clinical trials and therapeutic applications of this bioactive compound. Thus, a comprehensive review on Syringaresinol is essential to advance scientific understanding, assess its therapeutic applications, ensure safety, and guide future research efforts. This will ultimately contribute to its potential integration into clinical practice and public health. This study aims to provide a comprehensive overview of Syringaresinol on its sources and biological activities to provide insights into its therapeutic potential, and to provide a basis for high-quality studies to determine the clinical efficacy of this compound. Additionally, we explored the pharmacokinetics, toxicology, and drug development aspects of Syringaresinol to guide future research efforts. The review also discussed the limitations of current research on Syringaresinol and put forward some new perspectives and challenges, which laid a solid foundation for further study on clinical application and new drug development of Syringaresinol in the future., 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 © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Two-dimensional (2D) nanoarchitectonics involve the creation of functional material assemblies and structures at the nanoscopic level by combining and organizing nanoscale components through various strategies, such as chemical and physical reforming, atomic and molecular manipulation, and self-assembly. Significant advancements have been made in the field, with the goal of producing functional materials from these nanoscale components. 2D nanomaterials, in particular, have gained substantial attention due to their large surface areas which are ideal for numerous surface-active applications. In this review article, nanoarchitectonics of 2D nanomaterials based biomedical applications are discussed. We aim to provide a concise overview of how nanoarchitectonics using 2D nanomaterials can be applied to dental healthcare, with an emphasis on biosensing and drug delivery. By offering a deeper understanding of nanoarchitectonics with programmable structures and predictable properties, we hope to inspire new innovations in the dental bioapplications of 2D nanomaterials., 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 B.V.)

Preparation of ion-conductive hydrogels with excellent mechanics, good conductivity and adhesiveness is promising for flexible sensors, but remains a challenge. Here, we prepare a self-adhesive and ion-conductive hydrogel by introducing cellulose nanofibers (CNF) and ZnSO 4 into a covalently-crosslinked poly (acrylamide-co-2-acrylamide-2-methyl propane sulfonic acid) (P(AM-co-AMPS)) network. Owing to the hydrogen bonding and metal coordination interactions among P(AM-co-AMPS) chains, CNF, and Zn 2+ , the resulting P(AM-co-AMPS)/CNF/ZnSO 4 hydrogel exhibits high stretchability (1092 %), high toughness (244 kJ m -3 ), and skin-like elasticity (3.53 kPa). Moreover, the hydrogel has strong adhesion with different substrates by multiple non-covalent interfacial interactions. The SO 3 - on AMPS and COO - on CNF largely promptes the ionic migration (Zn 2+ , SO 4 2- ) through electrostatic interaction and hydrogen bonding, thus the hydrogel has high ion conductivity (5.85 S m -1 ). Finally, this hydrogel has high strain-sensitivity in a wide strain range, exhibiting great potential applications in wearable sensors., 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.)

Butyrylcholinesterase (BChE) plays a pivotal role in regulating acetylcholine (ACh) levels during the progression of Alzheimer's disease (AD), so emerged as an attractive target in AD treatment. Vasicine, a naturally occurring pyrroloquinazoline alkaloid, was identified as a natural BChE inhibitor (IC 50  = 1.47 ± 0.37 μM) from Traditional Chinese Medicine database. No any detailed research concerning the binding behavior of BChE with small molecule. As the first case, the inhibitory mechanism of vasicine on BChE was investigated using multi-spectroscopic methods (including fluorescence quenching, ANS fluorescence probe, three-dimensional fluorescence, time-resolved fluorescence, circular dichroism), isothermal titration calorimetry, surface plasmon resonance, and computational approaches. As a reversible and mixed inhibitor, vasicine displayed moderate affinity for BChE with an affinity constant K D of 2.111 μM, its binding process was characterized as a spontaneous exothermic reaction with reduced entropy, primarily driven by hydrogen bonding interactions. Vasicine quenched the fluorescence of BChE through both static and dynamic quenching mechanisms, leading to an increase in the α-helix content and surface hydrophobicity of BChE. Furthermore, the fluctuation of the skeleton atoms in the vasicine-BChE complex system remained stable, indicating good stability within the simulated physiological environment. In addition, vasicine exerted good safety for PC12 cells. Above findings provide molecular insights into the inhibitory mechanism of vasicine against BChE for the first time, and offer valuable information for future structure modification and therapeutic applications of vasicine as a BChE inhibitor., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yanfang Li reports financial support was provided by The Central Nervous System Drug Key Laboratory of Sichuan Province. 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.)

Different kinds of proteins interact with the digestible lipids in various ways, affecting the adsorption behavior of proteins and digestion. The ordered porous layer interferometry (OPLI) system was constructed by the silica colloidal crystal (SCC) films used to monitor the real-time binding assessment between bovine serum albumin (BSA), casein, fibrinogen, and triolein. The OPLI system reflected the changes in protein mass on the SCC films in real time through the migration of the interference spectrum of the SCC films, which was converted into the changes in optical thickness (ΔOT) that can be monitored. OPLI systematically studied the degradation of proteins by trypsin and found that the lipid layer enhanced the hydrolysis of trypsin to BSA and fibrinogen but weakened the degradation of trypsin to casein. The high OT of the lipid layer (10.45 nm) indicated that trypsin was more likely to adhere to the casein surface on the lipid layer than to hydrolyze casein. In contrast, the reduced OT (-6.40 nm) on the SCC films indicated that trypsin was more inclined to hydrolyze casein than to attach to casein. The OPLI system provided the technical basis for real-time tracking of protein hydrolysis behavior in complex food systems., 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.)

Current studies found that the peritumoral tissue of hepatocellular carcinoma (HCC) may be different from normal liver tissue based on proteomics, and related to progression, recurrence and metastasis of HCC. Our previous study proposed "peritumor microenvironment (PME)" to summarize the influence of peritumor tissue on occurrence and progression of HCC. Peritumor CYP2E1 activity was significantly elevated in HCC, and related to occurrence and progression of HCC. However, the effectiveness and mechanism of inhibiting CYP2E1 against HCC remain unclear. In this study, by integrating the advantages of proteomics and transcriptomics, we reanalyzed the various influencing factors in PME. Although there were large differences in the occurrence and progression, the immunity and inflammation still played crucial roles. Peritumor neutrophil were "pro-tumor" phenotype in the stage of progression, while it showed cytotoxicity for tumor cell in the occurrence stage. CYP2E1 activity is associated with peritumor neutrophil infiltration and occurrence of HCC. CYP2E1 inhibitor Q11 showed anti-tumor effects in an orthotopic HCC mouse model by promoting secretion of chemokines and infiltration of neutrophils in peritumor tissue. Overall, these findings provided a reasonable mechanism of anti-tumor effects of CYP2E1 inhibitors, which may be a new strategy for the prevention and treatment of HCC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hailing Qiao reports financial support was provided by National Natural Science Foundation of China. Hailing Qiao reports financial support was provided by Zhengzhou Science and Technology Bureau. 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.)

There are abundant glycosylated substances such as cellulose, hemicellulose, and phytochemical glycosides in plants, which could be converted into functional chemicals such as monosaccharides, oligosaccharides, and bioactive aglycones by cleavage of glycosidic bonds using glycoside hydrolases (GHs). Among those GHs, β-glucosidase and β-xylosidase are the rate-limiting enzymes for degrading cellulose and hemicellulose, respectively, and can convert a variety of glycosylated substances. These two enzymes play important roles in the high value use of plant resources and have great potential applications. However, the fragility of enzymes suggests there is an urgent need to improve the activity, stability and reusability of GHs under industrial conditions. Enzyme immobilization is an efficient approach to meet the need. Inorganic materials are preferred carriers for enzyme immobilization, since they possess high surface area, pore size, stability and long service life. Recently, many reports have showed that GHs immobilized on inorganic materials exhibit potential applications on industry and will benefit the process economy. The present review provides an overview of these reports from the perspectives of materials, strategies, activities, stability and reusability, as well as an insight into the related mechanisms, with a view to providing a reference for the GHs immobilization and their applications., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024. Published by Elsevier B.V.)

Lead (Pb) exposure is widely acknowledged as a risk factor for cardiovascular diseases. Previous studies have established neutrophil involvement in Pb-induced cardiovascular injuries; however, the underlying mechanisms remain unclear. To address this knowledge gap, the binding targets of Pb in neutrophils and their roles in regulating neutrophil extracellular trap (NET) formation were investigated. Furthermore, their impact on Pb-induced vascular inflammation and other cardiovascular injuries was studied in mice. Our findings indicate, for the first time, that Pb binds to β-actin in neutrophils, influencing NET formation. Inhibition of actin polymerization reduces the release of extracellular myeloperoxidase, neutrophil elastase, and citrullinated histone H3, indicating an impediment in NET formation. Furthermore, Pb exposure exacerbates blood pressure and vascular inflammation in vascular tissues, leading to abnormal aortic blood flow in mice. These injuries are potentially associated with NET formation, which is supported by the positive correlation between NETs and vascular inflammation. Importantly, the inhibition of actin polymerization mitigates Pb-induced vascular inflammation and regulates systolic blood pressure by reducing NET formation. Collectively, our findings provide novel insights into the mechanism underlying Pb-induced cardiovascular injury, contributing to the management of the escalating risk associated with Pb-induced cardiovascular damage., 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.)