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Ethnopharmacological Relevance: Penthorum chinense Pursh is a traditional Miao ethnomedicine rich in bioactive components, widely recognized for its hepatoprotective properties. However, the hepatoprotective effects of its flowers and leaves have not been individually elucidated., Aims of the Study: The objective of this study was to isolate and purify flavonoids-rich fractions from the flowers (PFF) and leaves (PLF) of P. chinense, and to assess their potential protective effects against oxidative, alcohol-induced, and free fatty acid (FFA) induced injury in hepatic cells., Materials and Methods: The P. chinense flowers and leaves flavonoids-rich fractions were extracted by the method optimized by response surface methodology, and the extracts were subsequently purified using petroleum ether and microporous column. The physical characteristics and component composition of PFF and PLF were analyzed by FT-IR and UPLC-MS/MS. The hepatoprotective activities of PFF and PLF were evaluated by the alcohol, H 2 O 2 , and FFA-induced hepatocyte injury cellular model in vitro. The protective effects of PFF and PLF on the hepatic cells were evaluated by assessing cell apoptosis rate, enzymes activities, mitochondrial membrane potential, and mRNA expression in relevant signaling pathways., Results: The results revealed that PFF was mainly composed of pinocembrin, quercitrin and quercetin, while PLF was predominantly composed of quercetin, pinocembrin, and kaempferol and their derivatives. PFF and PLF exhibited distinct effects on increasing the cell proliferation rate, regulating the MDA, GOT and GPT levels, and modulating the mRNA expression in apoptosis and antioxidant pathways in alcohol damaged LO2 cells. PFF exhibited superior efficacy in reducing cell apoptosis in alcohol-damage cells compared to PLF. Both PFF and PLF alleviated mitochondrial stress in H 2 O 2 -induced LO2 cells. Additionally, the PFF and PLF attenuated lipid accumulation and activated mRNA expressions in PPARα/ACOX1/CPT-1 lipid metabolism pathways, as well as Nrf2/ARE oxidative stress pathways., Conclusion: This study compared the hepatoprotective activities of flavonoids-rich fractions purified from the flowers and leaves of P. chinense. The results contribute to the enhanced development and utilization of various parts of P. chinense aimed at medical and health food applications., 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.)

This study focuses on evaluating new methods for the green extraction of saponin compounds from Polygonatum cyrtonema Hua (PCH). This study utilized a combination of carboxylic acid-based natural deep eutectic solvents (NADES) and various extraction techniques including conventional heat reflux-, ultrasound-, and microwave-assisted extraction. The primary objectives were to assess total saponin yield, antioxidant capacity, and enzyme inhibition efficiency. Additionally, the solvents and extracts were evaluated for their antibacterial activity. Oil-in-water (O/W) emulsions of NADES extracts were also characterized and analyzed for stability. Results indicated that three NADES systems were effective in extracting saponins, with choline chloride and lactic acid (ChCl-LA) system being the most efficient. The ChCl:LA extract exhibited antimicrobial and antioxidant activities superior to conventional organic solvent extracts. Additionally, it demonstrated maximum inhibitory activity (IC 50 values: 0.98 ± 0.03 and 1.46 ± 0.07 mg/mL, respectively) against α-glucosidase and α-amylase. The NADES extract as an aqueous phase significantly improved the stationarity of the O/W emulsion. Collectively, the study highlights the antimicrobial and technological advantages of NADES as a potential solvent for extracting saponin compounds from PCH., 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 study developed a biodegradable food film, incorporating bioactive components of Polygonatum cyrtonema extracted using natural deep eutectic solvents (NADES) into a matrix of chitosan and soy protein isolate. The films containing varying concentrations (0 %-5 %) of P. cyrtonema extract (PCE) were characterized. The addition of PCE improved the mechanical (+25.9 MPa for tensile strength), optical (+11.29 mm -1 for opacity), and thermal stability (-14.39 % for weight loss) of the films. The DPPH and ABTS radical scavenging rates increased by approximately 1.1 times and 0.5 times, respectively, and malondialdehyde formation reduced by 8 %. The films also effectively inhibited the growth of Staphylococcus aureus or Escherichia coli. The films showed complete biodegradability after 7 days. Using the NADES-PCE coated film reduced the weight loss of sweet cherries by 41.04 % while significantly decreasing the loss of hardness, total phenols, vitamin C, total soluble solids, and titratable acidity, thereby considerably extending the storage life of the sweet cherries. Overall, this study developed a new environmentally friendly packaging material and improved the functionality of the packaging film by leveraging natural plant extracts, demonstrating tremendous potential in the field of food preservation and packaging., 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.)

Purpose: Currently, detethering surgery (DS) is the modality most extensively utilized to treat primary Tethered cord syndrome (TCS). Disappointingly, some children without bladder impairment showed a deterioration of bladder function after surgery, which critically influences the health-related quality of life. It was hypothesized that the DS might have a significant effect on bladder function and psychology. Therefore, the purpose of this study was to investigate the effect of DS on bladder function and quality of life in children with primary TCS., Materials and Methods: A retrospective study of 83 patients aged 6 to 10 years who were diagnosed with TCS and underwent DS between 2022 and 2023. The urodynamic parameters and score, psychological-behavioral profile, and lower urinary tract symptoms were compared before and after DS. Additionally, the patients were divided into the normal group and the abnormal group according to the preoperative urodynamics parameters., Results: A total of 66 children fulfilled the criteria, with a mean age at surgery of 89.5 ± 13.7 months. There were statistically significant differences in bladder detrusor sphincter synergy and urodynamic score and no statistically significant difference in the remaining urodynamic parameters and psychological-behavioral items before and after DS. The proportion of bladder dysfunction that improved or did not worsen after surgery was higher in the Abnormal group than in the Normal group. Nevertheless, the detection rate of each psychological behavior abnormality in children with TCS was higher compared with that of normal children, both preoperatively and postoperatively., Conclusions: DS could not considerably ameliorate pre-existing bladder dysfunction and patients exhibiting non-progressive bladder dysfunction could be treated conservatively with close observation. TCS plagues patients all the time even if detethering. Psychological counseling for children with TCS should be strengthened after DS., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Limited whole genome sequencing (WGS) studies in Asian populations result in a lack of representative reference panels, thus hindering the discovery of ancestry-specific variants. Here, we present the South and East Asian reference Database (SEAD) panel ( https://imputationserver.westlake.edu.cn/ ), which integrates WGS data for 11,067 individuals from various sources across 17 Asian countries. The SEAD panel, comprising 22,134 haplotypes and 88,294,957 variants, demonstrates improved imputation accuracy for South Asian populations compared to 1000 Genomes Project, TOPMed, and ChinaMAP panels, with a higher proportion of well-imputed rare variants. For East Asian populations, SEAD shows concordance comparable to ChinaMAP, but outperforming TOPMed. Additionally, we apply the SEAD panel to conduct a genome-wide association study for total hip (Hip) and femoral neck (FN) bone mineral density (BMD) traits in 5369 genotyped Chinese samples. The single-variant test suggests that rare variants near SNTG1 are associated with Hip BMD (rs60103302, MAF = 0.0092, P = 1.67 × 10 -7 ), and variant-set analysis further supports the association (P slide_window  = 9.08 × 10 -9 , P gene_centric  = 5.27 × 10 -8 ). This association was not reported previously and can only be detected by using Asian reference panels. Preliminary in vitro experiments for one of the rare variants identified provide evidence that it upregulates SNTG1 expression, which could in turn inhibit the proliferation and differentiation of preosteoblasts., Competing Interests: Competing interests: S.-H.Y., W.-W.Z. and J.-Q.L. Y.S. are employee of KingMed Diagnostics Co., Ltd. The other authors have no competing interests to declare., (© 2024. The Author(s).)

The impact of various biopolymers on low-sodium condiments composed of salt, potassium chloride, sodium glutamate and Maillard reaction products with chicken flavor were evaluated in order to generate uniformly distributed low-sodium condiments. The addition of biopolymers reduced the sodium and potassium content of low sodium condiments, as well as improved the particle size, changed the particle morphology. The addition of different biopolymers had different effects on the color, flow characteristics, solubility, hygroscopicity and thermal stability of low sodium condiments. The low-sodium condiments with acceptable color, good flow characteristics, poor hygroscopicity, good solubility and good thermal stability are required for practical industrial applications. Considering the practical application of low-sodium condiments, with soluble starch and sodium carboxymethylcellulose were more suitable for subsequent use, Altogether, the biopolymer addition balances desirable properties such as thermal stability, hygroscopicity, and flow characteristics, making it an effective option for low-sodium alternatives without compromising on quality or functionality., 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: Nicastrin, a subunit of the γ-secretase complex, is encoded by the NCSTN gene and regulates notch signaling, it is involved in the pathogenesis of hidradenitis suppurativa (HS), Alzheimer disease (AD), and liver cancer. However, the animal models for studying HS are relatively scarce., Methods: CRISPR/Cas-mediated genetic engineering was used to generate targeted knockout offspring mice (C57BL/6J). Different doses (10 mg/kg, 20 mg/kg, and 30 mg/kg) and injection methods (subcutaneous/intraperitoneal/gavage injection) of tamoxifen were used to induce the construction of NCSTN knockout mice (mice model). The expressions of nicastrin, NICD1, hes1 in skin, brain, and liver tissue in mice model and wild-type (WT) mice were measured by qRT-PCR and IHC., Results: The construction of mice model was successfully induced by tamoxifen, knockout efficiency was 93%, there was no difference in knockout efficiency among three doses, injection methods, genders (P > 0.05). HS-like lesions appeared on the skin of NCSTN knockout mice after 1 month of treatment with tamoxifen, male mice had a higher number of skin lesions compared to female mice (male vs female = 76.5% vs 41.7%, P = 0.027). Compared with WT mice, the expressions of nicastrin (skin P = 0.0009, brain P = 0.0194, liver P = 0.0066), NICD1 (skin P = 0.0115, brain P = 0.0307, liver P = 0.008), hes1 (skin P = 0.0476, brain P = 0.0143, liver P = 0.0003) in mice model all decreased., Conclusions: The NCSTN knockout mouse might be employed as HS animal model; Reducing nicastrin may affect the expression of notch1-hes1 pathway molecules in skin, brain, and liver tissues; low dose (10 mg/kg/d) tamoxifen could be used to induce the deletion of the target gene in mice., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals and approved by the Fifth Clinical Medical College of Henan University of Chinese Medicine Institutional Review Board (ID: KY2021-004-01-D). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Aim: To assess the corneal high-order aberration (HOA) and its correlation with corneal morphological parameters in patients with bilateral keratoconus (KCN) and unilateral Vogt's striae., Methods: A total of 168 eyes of 84 patients with KCN, whose corneas had definite signs of unilateral Vogt's striae, were enrolled. Corneal HOA and morphological parameters were measured using Pentacam HR., Results: The corneal morphological parameters between KCN eyes with and without Vogt's striae were evidently different ( P <0.001). The 3 rd coma 90°, 4 th spherical aberration, 5 th coma 90°, root-mean-square (RMS) (total), and RMS (HOA) in the front, back surfaces and total cornea in KCN eyes with Vogt's striae were significantly higher than those in KCN eyes without Vogt's striae ( P <0.001). In KCN eyes with Vogt's striae, the 3 rd coma 90° and 4 th spherical aberration in the front surface and total cornea were negatively correlated with flat keratometry value (K1), steep keratometry value (K2), mean keratometry value (Km), maximum keratometry value (Kmax), anterior corneal elevation (ACE), and posterior corneal elevation (PCE; P <0.05). The 3 rd coma 90°, 4 th spherical aberration in back surface and RMS (total), RMS (HOA) in the front, back surfaces, total cornea were positively correlated with K1, K2, Km, Kmax, ACE, and PCE ( P <0.05)., Conclusion: Corneal HOA especially vertical coma and spherical aberration may increase when Vogt's striae appeared in KCN eyes. The scale of increase is significantly related with changes in corneal shapes., Competing Interests: Conflicts of Interest: Wei SS, None; Li Y, None; Wu ZQ, None; Liu JG, None; Du J, None; Li J, None; Zhang YH, None., (International Journal of Ophthalmology Press.)

Understanding salt tolerance mechanisms is crucial for addressing the global challenge of soil salinization and advancing sustainable agricultural practices. Dunaliella tertiolecta, thriving in up to 4.5 M NaCl, is a model for studying salt tolerance mechanisms. Two betaine aldehyde dehydrogenase (BADH) genes were identified in D. tertiolecta, namely DtBADH1 and DtBADH2. The phylogenetic analysis revealed that DtBADH1 had similarity to Pseudomonas aeruginosa BADH, while DtBADH2 has high homology to aldehyde dehydrogenase from Chlorella sorokiniana. The 3D models of DtBADH1 and DtBADH2 docking with betaine aldehyde were performed to further validate their binding site, interactions binding the protein and its substrate as well as the conserved amino acids responsible for enzyme activity. We also conducted RNA interference of DtBADH1 and DtBADH2 in D. tertiolecta. Compared to the wild type D. tertiolecta, both BADH-RNAi D. tertiolecta had fewer cell numbers and relatively lower glycine betaine content under high salinity. The findings suggest that both DtBADH1 and DtBADH2 play a crucial role in betaine synthesis, indicating their potential involvement in salt tolerance mechanisms at the molecular level. Additionally, these results highlight D. tertiolecta as a promising candidate for identifying salt stress-responsive genes, which could be utilized for engineering algae or crops to enhance their ability to withstand salinity stress., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

In this paper, we introduce a novel concordance-based predictive uncertainty (CPU)-Index, which integrates insights from subgroup analysis and personalized AI time-to-event models. Through its application in refining lung cancer screening (LCS) predictions generated by an individualized AI time-to-event model trained with fused data of low dose CT (LDCT) radiomics with patient demographics, we demonstrate its effectiveness, resulting in improved risk assessment compared to the Lung CT Screening Reporting & Data System (Lung-RADS). Subgroup-based Lung-RADS faces challenges in representing individual variations and relies on a limited set of predefined characteristics, resulting in variable predictions. Conversely, personalized AI time-to-event models are hindered by transparency issues and biases from censored data. By measuring the prediction consistency between subgroup analysis and AI time-to-event models, the CPU-Index framework offers a nuanced evaluation of the bias-variance trade-off and improves the transparency and reliability of predictions. Consistency was estimated by the concordance index of subgroup analysis-based similarity rank and model prediction similarity rank. Subgroup analysis-based similarity loss was defined as the sum-of-the-difference between Lung-RADS and feature-level 0-1 loss. Model prediction similarity loss was defined as squared loss. To test our approach, we identified 3,326 patients who underwent LDCT for LCS from 1/1/2015 to 6/30/2020 with confirmation of lung cancer on pathology within one year. For each LDCT image, the lesion associated with a Lung-RADS score was detected using a pretrained deep learning model from Medical Open Network for AI (MONAI), from which radiomic features were extracted. Radiomics were optimally fused with patient demographics via a positional encoding scheme and used to train a neural multi-task logistic regression time-to-event model that predicts malignancy. Performance was maximized when radiomics features were fused with positionally encoded demographic features. In this configuration, our algorithm raised the AUC from 0.81 ± 0.04 to 0.89 ± 0.02. Compared to standard Lung-RADS, our approach reduced the False-Positive-Rate from 0.41 ± 0.02 to 0.30 ± 0.12 while maintaining the same False-Negative-Rate. Our methodology enhances lung cancer risk assessment by estimating prediction uncertainty and adjusting accordingly. Furthermore, the optimal integration of radiomics and patient demographics improved overall diagnostic performance, indicating their complementary nature., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kyle J. Lafata, Joseph Y. Lo, Fakrul Islam Tushar reports financial support was provided by National Institute of Biomedical Imaging and Bioengineering. Kyle J. Lafata, Joseph Y. Lo reports financial support was provided by National Cancer Institute. 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. Published by Elsevier B.V.)

Global warming has induced an increase in the intensity and frequency of summer extreme high temperature events in Chinese subtropical forest, which contributes to a large component of net primary ecological production among global forests. However, how summer extreme high temperature events would influence tree radial growth in these humid subtropical forest remains unclear. We investigated the non-linear response of tree radial growth to temperature, soil moisture and their mixed effect across broad latitude gradients in Chinese subtropical forests, using a method of modelling cambial growth kinetics of Schima superba. The results showed that radial growth was constrained by summer extreme high temperatures and this limiting effect relieved from south to north. However, we also found a growth constraint imposed by soil moisture during spring and autumn, which intensified toward northern sites. Coincidentally, the radial growth pattern showed a distinct transition from bimodal to unimodal from South to North sites, with no significant changes in cambium phenology over the time scale from 1986 to 2014 being observed. In general, we determined that limitation of extreme high temperatures on radial growth relieve with increasing latitude in subtropics. This study provides a theoretical basis for promoting the accurate assessment of carbon sink potential and for predicting future forest dynamics in subtropics., 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.)

Background: Many studies have shown that the COVID-19 pandemic has increased the risk of suicidal tendencies among the public. However, there is limited research reporting on the changing trends in suicidal ideation after 2020 in the context of the long-term normalization of COVID-19 prevention and control measures in China., Methods: The self-administered online questionnaire was adopted to collect 12-month suicidal ideation, depressive symptoms, anxiety symptoms, stress, and some demographic information from university students by convenient cluster sampling in Shandong, Shaanxi, and Jilin Provinces, China. Multivariate logistic regressions were performed to assess the association between different factors and suicidal ideation., Results: The prevalence of 12-month suicidal ideation from 2021 to 2023 among university students was 3.89 %, 5.81 %, and 4.33 %, respectively, showing a trend of first increasing and then decreasing. The trends presented a similar tendency in the subgroups according to gender, majors, and grades, except among urban freshman-year students. The associated factors of suicidal ideation were different among university students in different surveys. However, female gender, poor mental health, and depressive symptoms were linked to a higher risk of suicidal ideation., Limitations: More representative large-scale longitudinal studies should be used to monitor the suicidal behavior of university students., Conclusions: The prevalence of 12-month suicidal ideation among Chinese university students exhibited a pattern of initial increase followed by a subsequent decrease from 2021 to 2023. Despite the complete lifting of COVID-19 prevention and control measures in China, the prolonged three-year epidemic may have enduring adverse effects on university students, underscoring the ongoing importance of providing continuous mental health services to this population., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microbial ammonia oxidation plays an important role in nitrogen (N 2 ) cycling in natural and man-made systems. Heterotrophic microorganisms that oxidize ammonia were observed more than a century ago; however, the underlying molecular mechanism of ammonia oxidation is still mysterious. Dirammox (direct ammonia oxidation to N 2 ) is a newly described heterotrophic ammonia oxidation process in which ammonia or its organic amine is oxidized into hydroxylamine and then directly converted to N 2 gas without the involvement of nitrite and nitrate. As demonstrated with Alcaligenes species, the conversion of ammonia to hydroxylamine is mediated by the dnf genes, and hydroxylamine conversion to N 2 is considered both a biotic and abiotic process. Dirammox is different from the N 2 -producing processes of nitrification-denitrification and anaerobic ammonia oxidation (anammox), in which nitrite or nitrate is involved. Here, we review the discovery of dirammox, progress toward understanding its genetics, biochemistry, physiology, and ecology, and future perspectives and directions., Competing Interests: Declaration of Competing Interest The authors disclose no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Plastic additives provide plastics with excellent functions such as plasticizing, flame retardant, and antioxidant properties and are widely used in various plastics. Of these, 189 plastic additives have been included in the European Union's Candidate List of substances of very high concern （SVHCs） due to their potential environmental and health risks. These SVHCs are mainly used in PVC, PUR, and PE plastics and in the packaging, automotive, construction, electronic and electrical equipment, and textile sectors. Plasticizers and flame retardants are the most widely used and therefore the focus of SVHC risk assessment and risk management. Existing studies have carried out material flow analysis （MFA） for SVHCs in plastics, revealing the environmental and health risks of typical flame retardants and plasticizers throughout the product life cycle, such as polybrominated diphenyl ethers （PBDEs）, hexabromocyclododecane （HBCD）, and phthalic acid esters （PAEs）. A large amount of SVHCs enter waste streams at the end of the product life cycle, highlighting the importance of strengthening waste management for SVHCs risk management. In addition to the release of SVHCs from plastic products into the environment, plastic leakage is another important source of environmental release of SVHCs. Plastic debris that have been in the environment for a long time continue to release SVHCs and pose a long-term threat to the ecosystem and human health. In the future potentially hazardous chemicals must be crucially identified in different types of plastics and to assess their environmental release during their life cycle, in particular by establishing a database on hazardous chemicals in plastics and measuring emission factors, optimizing dynamic material flow analysis （d-MFA）, as well as studying the release mechanisms of hazardous chemicals from plastic leakage.

Aims: Methicillin-resistant Staphylococcus aureus (MRSA) is an important zoonotic pathogen with multidrug-resistant phenotypes increasingly prevalent in both human and veterinary clinics. This study evaluated the potential of auranofin (AF) as an antibiotic adjuvant to enhance the anti-MRSA activity of florfenicol (FFC) and established a pharmacokinetic/pharmacodynamic (PK/PD) model to compare the efficacy of FFC alone or in combination with AF against MRSA., Methods and Results: We observed an increased susceptibility and significant synergistic effects of MRSA to FFC in the presence of AF. The combination treatment of FFC and AF significantly inhibited MRSA biofilm formation and decreased the metabolic activity of mature biofilms. Importantly, AF fully restored the efficacy of FFC in both Galleria mellonella larvae and murine models. PK/PD studies demonstrated that the AUC24h/MIC targets required to achieve the bacteriostatic and bactericidal effects were significantly lower with the combination therapy compared to florfenicol monotherapy., Conclusions: These results reveal the potential of AF as a novel adjuvant to improve the efficacy of FFC in treating MRSA invasive infections and provide valuable PK/PD insights for designing effective combination therapies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Ependymal cells (EpCs), as a potential stem cell niche, have gained interest for their potential in vivo stem cell therapy for spinal cord injury (SCI). Heterogeneity of spinal EpCs may contribute to differences in the ability of spinal EpCs to proliferate, differentiate and transition after injury, while there is limited understanding of the regulation of these events. Our research found that ezrin (Ezr) was expressed highly in EpCs of the spinal cord, and its upregulation rapidly occurred after injury (6 h). It remained consistently highly expressed in proliferating EpCs, this occurs before pathological accumulation of it occurs in other glial and immune-related cells. Differential expression of Ezr, Arg3, Pvalb, Ccnd1, and Gmpr characterized distinct responses of EpCs to injury activity. Also, we uncovered the dynamic regulatory behavior of immature EpCs after injury. In contrast to constitutive expression in parenchymal tissues, injury factors upregulated guanosine monophosphate reductase (Gmpr) in arrested EpCs, unveiling a distinctive mechanism to regulate proliferation in EpCs following spinal cord injury., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose. The following are the supplementary data related to this article. Supplementary data to this article can be found online at https://doi.org/10.1016/j.nbd.2024.106746., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The extraction of polysaccharides from stem barks and flowers of Magnolia officinalis were optimized using response surface methodology and the maximum yields were 4.12 ± 0.06 % and 5.5 ± 0.08 %, respectively. Three homogeneous polysaccharides including MOBP-I, MOBP-II and MOFP-I were further purified and their compositional characterization were compared. Molecular weights of MOBP-I, MOBP-II and MOFP-I were 5.9 × 10 3 , 6.8 × 10 3 and 3.9 × 10 4  Da, respectively. Gas chromatography (GC) analysis suggested that MOBP-I, MOBP-II and MOFP-I were composed of rhamnose, arabinose, mannose, glucose and galactose at different ratios and exhibited different appearance and glycosidic linkages. MOFP-I but not MOBP-I and MOBP-II had three helix structures. MOBP-I, MOBP-II and MOFP-I showed significant hypoglycemic and photoprotection capacities with different efficacy. MOBP-I had greater hypoglycemic activity, as evidenced by the increased α-glucosidase inhibition activity and glucose consumption in insulin-resistant HepG2 cells. MOBP-II and MOFP-I were more powerful in reversing ultraviolet-B (UVB)-irradiated photoaging of HaCaT cells. The difference of polysaccharides compositions might explain for their bioactivity discrepancy., 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.)

Renal fibrosis is the major pathological changes of Chronic kidney disease (CKD). Piezo1, a mechanical sensitive ion channel, is implicated in organ fibrosis. However, the precise role of Piezo1 in CKD fibrosis is unknown. The aims of this study were to identify that the role of Piezo1 in CKD fibrosis and its potential involvement of mitochondrial dysfunction. We performed the study with the Piezo1 agonist Yoda1, Bax inhibitor BAI1, Piezo1 inhibitor GsMTx4 and detected the injury, fibrosis, apoptosis markers and mitochondrial dysfunction. The results showed that the levels of apoptosis, mitochondrial dysfunction, injury and fibrosis increased in TCMK-1 cells after treatment with Yoda1. However, these changes that induced by Yoda1 were relieved by BAI1. Similarly, inhibition Piezo1 with GsMTx4 also partly relieved the renal injury, renal fibrosis, apoptosis and mitochondrial dysfunction in vivo and vitro. In conclusion, we found Piezo1 promoted the initiation and development of renal fibrosis and inhibiting Piezo1 improved the fibrosis.

Natural carotenoids from microalgae have received more attention as an alternative source. In this study, fulvic acid (FA), a plant growth regulator, was used to enhance carotenoid accumulation in microalgae Dunaliella bardawil rich in lutein. However, the addition of FA promoted pigment synthesis but also exhibited an inhibitory effect on biomass. Therefore, the optimization of culture conditions was performed to further enhance carotenoid accumulation, including high light stress (10,000 lx) and the two-stage cultivation comprising 1-aminocyclopropane-1-carboxylic acid (ACC) and FA. Under both culture conditions, the growth inhibition caused by FA was alleviated, leading to a further increase in the contents of chlorophylls and carotenoids. HPLC analysis revealed that the production of lutein, α-carotene and β-carotene increased by 0.44-, 0.37- and 0.54-fold under the treatment of 400 mg/L FA with high light intensity and 0.91-, 1.15-0.29-fold under the two-stage cultivation comprising 11 mM ACC and 500 mg/L FA. Furthermore, algal cells under FA treatment and the two-stage cultivation stained with Bodipy505/515 emitted stronger fluorescence under a laser confocal microscope, suggesting that lipid accumulation was increased. Additionally, the transcription levels of carotenogenic genes were also found to be up-regulated by qRT-PCR. These results indicated an enhancement in both the storage capacity and synthesis of carotenoids in D. bardawil. This study revealed the potential application of plant growth regulators in promoting carotenoid accumulation in D. bardawil which could be further improved by optimizing the culture conditions, providing a reference for efficient carotenoid production in microalgae., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Dunaliella can accumulate more β-carotene (10 % or even more of the dry weight of cells) than any other species. Lycopene β-cyclase (LcyB) is the key enzyme in the catalysis of lycopene to β-carotene. In the present research, we used Escherichia coli BL21 (DE3) as host to construct two different types of engineering bacteria, one expressing the D. bardawil LcyB and the other expressing the orthologue Erwinia uredovora crtY. The catalytic ability of LcyB and CrtY were evaluated by comparing the β-carotene yields of the two E. coli BL21(DE3) strains, whose salt tolerance was simultaneously compared by cultivated them under different NaCl concentrations (1 %, 2 %, and 4 %). We also interfered with the LcyB gene to investigate the effect of LcyB in D. bardawil. Results displayed that the β-carotene yield of the LcyB-transformant significantly increased by about 48 % compared with the crtY-transformant. Additionally, LcyB was verified to be able to enhance the salt tolerance of E. coli BL21 (DE3). It is concluded that D. bardawil LcyB not only has better catalytic ability but also is able to confer salt tolerance to cells. Interfering D. bardawil LcyB induced the low expression of LcyB and the changes of growth and carotenoids metabolism in D. bardawil., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Since the onset of COVID-19, respiratory diseases have emerged as a focal concern within the field of public health. This study aims to reveal the prevalence of acute respiratory infectious diseases by screening antipyretic, antiviral, and antibiotic biomarkers through wastewater analysis. Samples were collected over a seven-day period each year in 2022, 2023, and 2024 from a northern city in China, assessing the concentrations of two antipyretics (paracetamol and ibuprofen), one antiviral drug (oseltamivir), eleven antibiotics, and three pathogens (influenza A, influenza B, and Mycoplasma pneumoniae). The usage of most antipyretics and antibiotics was higher in 2023 and 2024, primarily due to the outbreak of COVID-19 in 2023 and the prevalence of influenza A, influenza B, and Mycoplasma pneumoniae in 2024. The prevalence assessed using antipyretics (2.68 %) and pathogens (2.70 %) demonstrated a high degree of consistency, whereas the prevalence estimated using antibiotics and antiviral drugs was only 0.53 % and 0.36 %, respectively. Antibiotics are generally used to treat a broad spectrum of bacterial infections rather than targeting a specific pathogen, so their presence in wastewater may not directly reflect the prevalence of a particular disease. In contrast, antipyretics and specific pathogens exhibit a stronger correlation, suggesting that they may serve as more reliable biomarkers than antiviral and antibiotic drugs. The research findings offer alternative biomarkers, such as antipyretics, aside from pathogens, for the assessment of acute respiratory infectious diseases., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Apoptosis associated speck like protein containing a card (ASC), the key adaptor protein of the assembly and activation of canonical inflammasomes, has been found to play a significant role in neuroinflammation after spinal cord injury (SCI). The previous studies indicated that widely block or knockout ASC can ameliorate SCI. However, ASC is ubiquitously expressed in infiltrated macrophages and local microglia, so further exploration is needed on which type of cell playing the key role. In this study, using the LysM cre ;Asc flox/flox mice with macrophage-specifc ASC conditional knockout (CKO) and contusive SCI model, we focus on evaluating the specific role of ASC in lysozyme 2 (LysM) + myeloid cells (mainly infiltrated macrophages) in this pathology. The results revealed that macrophage-specifc Asc CKO exhibited the follow effects: (1) A significant reduction in the numbers of infiltrated macrophages in the all phases of SCI, and activated microglia in the acute and subacute phases. (2) A significant reduction in ASC, caspase-1, interleukin (IL)-1β, and IL-18 compared to control mice. (3) In the acute and subacute phases of SCI, M1 subset differentiation was inhibited, and M2 differentiation was increased. (4) Histology and hindlimb motor recoveries were improved. In conclusion, this study elucidates that macrophage-specific ASC CKO can improve nerve function recovery after SCI by regulating M1/M2 polarization through inhibiting ASC-dependent inflammasome signaling axis. This indicates that ASC in peripheral infiltrated macrophages may play an important role in SCI pathology, at least in mice, could be a potential target for treatment., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Studying differences in transcriptomes across various development stages of insects is necessary to uncover the physiological and molecular mechanism underlying development and metamorphosis. We here present the first transcriptome data generated under Illumina Hiseq platform concerning Zeugodacus tau (Walker) larvae from Nanchang, China. In total, 11,702 genes were identified from 9 transcriptome libraries of three development stages of Z. tau larvae. 7219 differentially expressed genes (DEGs) were screened out from the comparisons between each two development stages of Z. tau larvae, and their roles in development and metabolism were analyzed. Comparative analyses of transcriptome data showed that there are 5333 DEGs between 1-day and 7-day old larvae, consisting of 1609 up-regulated and 3724 down-regulated genes. Expressions of DEGs were more abundant in L7 than in L1 and L3, which might be associated with metamorphosis. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested the enrichment of metabolic process. KOG annotation further confirmed that 20-hydroxyecdysone (20E) pathway related genes Cyp4ac1&#95;1, Cyp4aa1, Cyp313a4&#95;3 were critical for the biosynthesis, transport, and catabolism of secondary metabolites and lipid transport and metabolism. Expression patterns of 8 DEGs were verified using quantitative real-time PCR (RT-qPCR). This study elucidated the DEGs and their roles underlying three development stages of Z. tau larvae, which provided valuable information for further functional genomic research., 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.)

Diabetic foot ulcer (DFU) is a common chronic complication of diabetes. This complication is characterized by the formation of ulcers that are difficult to heal on the skin of the foot. Ulcers can negatively affect patients' quality of life, and improperly treated lesions can result in amputation and even death. Traditionally, the severity and type of foot ulcers are determined by doctors through visual observations and on the basis of their clinical experience; however, this subjective evaluation can lead to misjudgments. In addition, quantitative methods have been developed for classifying and scoring are therefore time-consuming and labor-intensive. In this paper, we propose a reconstruction residual network with a fused spatial-channel attention mechanism (FARRNet) for automatically classifying DFUs. The use of pseudo-labeling and Data augmentation as a pre-processing technique can overcome problems caused by data imbalance and small sample size. The developed model's attention was enhanced using a spatial channel attention (SPCA) module that incorporates spatial and channel attention mechanisms. A reconstruction mechanism was incorporated into the developed residual network to improve its feature extraction ability for achieving better classification. The performance of the proposed model was compared with that of state-of-the-art models and those in the DFUC Grand Challenge. When applied to the DFUC Grand Challenge, the proposed method outperforms other state-of-the-art schemes in terms of accuracy, as evaluated using 5-fold cross-validation and the following metrics: macro-average F1-score, AUC, Recall, and Precision. FARRNet achieved the F1-score of 60.81%, AUC of 87.37%, Recall of 61.04%, and Precision of 61.56%. Therefore, the proposed model is more suitable for use in medical diagnosis environments with embedded devices and limited computing resources. The proposed model can assist patients in initial identifications of ulcer wounds, thereby helping them to obtain timely treatment., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC 50 value of 15.07 ± 1.19 μM., 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: Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine malignancy characterized by its complex tumor microenvironment (TME) and high recurrence rates, posing challenges to accurate prognosis and effective treatment. Identifying prognostic biomarkers is essential for improving patient stratification and guiding therapeutic strategies., Methods: Using single-cell transcriptome analysis combined with H&E and multiplex immunofluorescence staining, we identified a subpopulation of tumor cells in LG-ESS and further validated the association of this subpopulation and its characteristic genes with LG-ESS prognosis by molecular characterization and bulk transcriptome data., Results: Our analysis reveals multiple cellular subpopulations within the tumor tissue, particularly a tumor cell subpopulation among them which is associated with poor prognosis. Originating from normal stromal fibroblasts, this subpopulation appears to play a crucial role in TME remodeling, smooth muscle cell behavior, and potentially in tumorigenesis and metastasis. Of particular interest in this subpopulation is the highly expressed FGF12 gene, which is significantly associated with a shortened survival in ESS, highlighting its potential as a prognostic biomarker., Conclusion: Our study reveals the complexity of TME within the LG-ESS and highlights the role that tumor cell subpopulations play in disease progression and patient prognosis. The identification of FGF12 as a prognostic biomarker suggests a new approach for the personalized treatment and prognosis monitoring of patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Miao, Dong, Zhou, Thiel, Li, Cai, Yuan, Wang, Jin, Yang, Wang, Frey, Gaipl, Ma and Zhou.)

Purpose: Mitochondria are involved in septic shock and inflammatory response syndrome, which severely affects the life security of patients. It is necessary to recognize and explore the immune-mitochondrial genes in septic shock., Methods: The GSE57065 dataset was acquired from the Gene Expression Omnibus (GEO) database and filtered by limma and the weighted correlation network analysis (WGCNA) to identify mitochondrial-related differentially expressed genes (MitoDEGs) in septic shock. The function of MitoDEGs was analyzed using the Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), respectively. The Protein-Protein Interaction (PPI) network composed of MitoDEGs was established using Cytoscape. Support Vector Machine Recursive Feature Elimination (SVM-RFE), Random Forest (RF), and Least Absolute Shrinkage and Selection Operator (LASSO) were used to identify diagnostic MitoDEGs, which were validated using receiver operating characteristic (ROC) analysis and Quantitative Real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR). Furthermore, the infiltration of immunocytes was analyzed using CIBERSORT, and the correlation between diagnostic MitoDEGs and immunocytes was explored using Spearman., Results: A total of 44 MitoDEGs were filtered, and functional enrichment analysis showed they were associated with mitochondrial function, and the PPI network had 457 nodes and 547 edges. Four diagnostic genes, MitoDEGs, PGS1, C6orf136, THEM4, and EPHX2, were identified by three machine learning algorithms, and qRT-PCR results obtained similar expression levels as bioinformatics analysis. Furthermore, the diagnostic model constructed by the diagnostic genes had fine diagnostic efficacy. Immunocyte infiltration analysis showed that activated immunocytes were abundant and correlated with hub genes, with neutrophils accounting for the largest proportion in septic shock., Conclusions: In this study, we recognized four immune-mitochondrial key genes (PGS1, C6orf136, THEM4, and EPHX2) in septic shock and designed a novel gene diagnosis model that provided a new and meaningful way for the diagnosis of septic shock., Competing Interests: Declarations. Ethics approval and consent to participate: The experiments were approved by the Ethics Committee of Shanghai Fifth People’s Hospital, Fudan University (Approval No.: 2023-196). Written informed consent was acquired from each participant. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: We performed the present study to better elucidate the correlation of nitric oxide synthase 3 (NOS3) gene polymorphism with the risk of pulmonary arterial hypertension (PAH)., Material/methods: According to the designed search strategy, a systematic literature search was performed through the PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP and Wan Fang databases to collect published case-control studies on the correlation between NOS3 gene polymorphism and PAH. The search deadline was December 26, 2023. Two reviewers independently screened the literature, extracted data and evaluated the quality according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. The odds ratio (OR) and 95 % confidence interval (CI) of the genotype distribution were used as the effect indicators., Results: A total of 11 eligible studies were included, involving three single nucleotide polymorphism (SNP) sites of the NOS3 gene: G894T (rs1799983), 4b/4a (rs61722009), and T-786C (rs2070744). The meta-analysis revealed that for PAH analysis, 4 genetic models of NOS3 G894T polymorphism increased the risk of PAH: the allele model (T vs G, OR = 1.9, 95%CI [1.16, 3.11],P = 0.01), the homozygote model (GG vs TT, OR = 1.91, 95%CI [1.04, 3.51], P = 0.04), the heterozygote model (GG vs GT, OR = 3.19, 95%CI [1.65, 6.19], P = 0.0006) and the dominant model (GT + TT vs GG, OR = 3.06, 95%CI [1.54, 6.09], P = 0.001). In the subgroups analysis, the NOS3 G894T polymorphism was found to be associated with the risk of PAH subgroups, including CHD combined with PAH and COPD combined with PAH, Particularly, there is a highly significant correlation with CHD combined with PAH. 2 genetic models of NOS3 4b/4a polymorphism increased the risk of PAH: the homozygote model (BB vs AA, OR = 2.1, 95%CI [1.02, 4.35], P = 0.04) and the recessive model (BB + BA vs AA, OR = 2.55, 95%CI [1.27, 5.11], P = 0.009). In the subgroups analysis, the NOS3 4b/4a polymorphism was found to be associated with the susceptibility of CHD combined with PAH. The results of the combined analysis of each gene model of NOS3 T-786C gene polymorphism sites were not statistically significant, and their P values were all>0.05. The NOS3 G894T and NOS3 4b/4a gene polymorphism had been found to be associated with the risk of PAH in different regional and racial subgroups. In contrast to the NOS3 G894T gene polymorphism, which increased the risk of PAH development in the yellow race subgroup, the NOS3 4b/4a gene polymorphism reduced the risk of PAH development in the white race subgroup and was a protective factor., Conclusions: The NOS3 G894T (rs1799983) and NOS3 4b/4a (rs61722009) gene polymorphism have a strong correlation with the risk of PAH, with this association varying among different regions and ethnicities. However, it is still necessary to expand the sample size and conduct further studies to confirm whether the NOS3 T-786C (rs2070744) polymorphism tends to increase the incidence of PAH., Competing Interests: Conflict of interest The authors declared that there have no conflicts of interest to this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The adolescent years are a period of profound change, both physically and psychologically. For many, these years are marked by excitement and exploration, but for others, they are fraught with challenges that can lead to significant mental health issues. Depression, in particular, has become an increasingly prevalent concern among adolescents worldwide, and its multifaceted etiology requires a comprehensive approach to understanding and intervention. A recent study on the relationships among negative life events, dysfunctional attitudes, social support, and depressive symptoms in Chinese adolescents offers valuable insights into the complex interplay between various factors contributing to adolescent depression. The authors explore a moderated mediation model to better understand how these factors interact with and contribute to the onset of depression. This article aims to delve into the key findings of the study, highlight its implications for clinical practice, and encourage further research in this critical area., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear., Method: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication. The STN LFP features that characterised different sleep stages, correlated with arousal and sleep fragmentation index, and preceded stage transitions during N2 and REM sleep were analysed., Results: Both beta and low gamma oscillations in non-rapid eye movement (NREM) sleep increased with the severity of sleep disturbance (arousal index (ArI)-beta NREM : r=0.9, p=0.0001, sleep fragmentation index (SFI)-beta NREM : r=0.6, p=0.0301; SFI-gamma NREM : r=0.6, p=0.0324). We next examined the low-to-high power ratio (LHPR), which was the power ratio of theta oscillations to beta and low gamma oscillations, and found it to be an indicator of sleep fragmentation (ArI-LHPR NREM : r=-0.8, p=0.0053; ArI-LHPR REM : r=-0.6, p=0.0373; SFI-LHPR NREM : r=-0.7, p=0.0204; SFI-LHPR REM : r=-0.6, p=0.0428). In addition, long beta bursts (>0.25 s) during NREM stage 2 were found preceding the completion of transition to stages with more cortical activities (towards Wake/N1/REM compared with towards N3 (p<0.01)) and negatively correlated with STN spindles, which were detected in STN LFPs with peak frequency distinguishable from long beta bursts (STN spindle: 11.5 Hz, STN long beta bursts: 23.8 Hz), in occupation during NREM sleep (β=-0.24, p<0.001)., Conclusion: Features of STN LFPs help explain neurophysiological mechanisms underlying sleep fragmentations in PD, which can inform new intervention for sleep dysfunction., Trial Registration Number: NCT02937727., Competing Interests: Competing interests: Luming Li and Hongwei Hao serve on the scientific advisory board for Beijing Pins Medical Co., Ltd and are listed as inventors in issued patents and patent applications on the deep brain stimulator used in this work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Early evaluation of radiation sensitivity in lung cancer patients can facilitate the transition to personalized treatment strategies. To this end, we assessed the capability of 89 Zr-anti-γH2AX-TAT microPET imaging in determining the radiosensitivity of lung cancer xenograft models. We prepared and conducted quality control on 89 Zr-anti-γH2AX-TAT. The radiosensitivity of human non-small cell lung cancer cells (H460) and adenocarcinoma cells (A549) was analyzed through clonogenic survival experiments. Additionally, the role of γH2AX as a biomarker for radiosensitivity was validated by quantifying γH2AX foci via fluorescence staining. Subsequently, the H460 and A549 xenograft mouse models were subjected to irradiation, followed by 89 Zr-anti-γH2AX-TAT microPET imaging. Concurrently, we performed immunofluorescence staining for γH2AX in tumor tissues to establish a correlation between the uptake of 89 Zr-anti-γH2AX-TAT and γH2AX expression., Results: The surviving fraction 2 Gy (SF2) values of H460 and A549 indicating that A549 adenocarcinoma has higher radiosensitivity. The cell immunofluorescence experiment showed that the repair of γH2AX foci in H460 cells after irradiation was significantly higher than that in A549 cells, which also confirmed that A549 has higher radiosensitivity. The microPET imaging results showed the uptake of 89 Zr-anti-γH2AX-TAT in the tumor of the A549 models after radiotherapy was higher than H460 models. The immunofluorescence staining of tumor tissue confirmed that the expression level of γH2AX was higher and the correlation with microPET imaging uptake was good., Conclusion: 89 Zr-anti-γH2AX-TAT allows PET imaging of radiosensitivity in lung cancer xenograft models, and is expected to become an early evaluation method for lung cancer radiosensitivity., Competing Interests: Declarations Ethics approval and consent to participate All animal procedures in the in vivo study were performed in accordance with the 1986 UK Animals (Scientific Procedures) Act and approved by the ethics committee with the ethics approval number SBQDL-2022-077. Consent for publication Not applicable. Competing interests No potential conflicts of interest were disclosed., (© 2024. The Author(s).)

Liver fibrosis (LF) is a common sequela to diverse chronic liver injuries, leading to rising rates of cirrhosis and hepatocellular carcinoma (HCC). As the medicinal and edible homologous material, traditional teas have exhibited promising applications in the clinical management of liver fibrosis. Here, we generated a liver fibrosis mouse model to explore the potent therapeutic ability of Ampelopsis grossedentata (AG) tea on this condition by multi-omics analysis. The biochemistry results pointed towards mitigated increases of ALT, AST, TBIL, and ALP triggered by BDL in the AG-treated group. Examination using H&E and Sirius Red staining revealed severe liver injuries, inflammation infiltration, amplified fibrosed regions, and the creation of bile ducts, all of which were fallout from BDL. Immunohistochemistry findings also implicated a noteworthy upregulation of the HSC activation marker α-smooth muscle actin (α-SMA) and the fibrosis marker collagen I in the BDL group. However, these symptoms demonstrated a significant improvement in the group treated with 100 mg/kg AG. Findings from the Western Blot test corroborated the prominent elevation of TNF-α, col1a1, α-SMA, and TGF-β, instigated by BDL, while AG treatment meaningfully modulated these proteins. Furthermore, our study underscored the potential involvement of several microbiota, such as Ruminococcaceae UCG-014, Eubacterium Ruminantium, Ruminococcus 1, Christensenellaceae R-7, Acetatifactor, Dubosiella, Parasutterella, Faecalibaculum, and Defluviitaleaceae UCG-011, in the progression of liver fibrosis and the therapeutic efficacy of AG. This investigation shows that during the process of AG ameliorating BDL-induced liver fibrosis, bile acid derivatives such as CDCA, TCDCA, 3-DHC, UCA, DCA, among others, play significant roles. In this study, we identified that several non-bile acid metabolites, such as Deltarasin, Thr-Ile-Arg, etc., are entailed in the process of AG improving liver fibrosis., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Hypertension is one of the major risk factors for morbidity and mortality worldwide. In this study, Mendelian randomization was utilized to investigate how dietary supplement intake can impact hypertension based on circulating plasma metabolite genome-wide association study (GWAS) datasets, protein quantitative trait loci (pQTLs) of plasma proteins, and multiple public summary-level GWAS data. Pathway enrichment analysis combined with the results of inverse variance weighted Mendelian randomization revealed that a lower risk of hypertension was associated with the dietary intake of glucosamine, an anti-inflammatory supplement: odds ratio (OR) (95% CI): 0.888 (0.824-0.958). Additionally, glucosamine 6-phosphate N-acetyltransferase was identified as a protective factor against hypertension, OR (95% CI): 0.995 (0.992-0.998), shedding light on the potential protective mechanism of glucosamine. Mediation Mendelian randomization indicated that the protective effect of glucosamine metabolism was mediated by glutaminyl-peptide cyclotransferase, with a mediation proportion of 12.1% (5.9-18.2%), p < 0.05. This study offers new insights into preventive strategies for individuals with hypertension risk.

Tree-ring widths contain valuable historical information related to both forest disturbances and climate variability and changes within forests. However, current methods are still unable to accurately distinguish between disturbances and climate signals in tree rings, especially in the case of climate anomalies. To address this issue, we developed a novel method, called Growth Trends Clustering (GTC) that uses the distribution characteristics of tree-ring widths within a stand to distinguish the effects of climate and other forest disturbances. GTC employed a Gaussian mixture model to fit the probability density distribution of annual ring-width index (RWI) in a stand. Discriminative criteria were established to cluster diverse sub-distributions from the Gaussian mixture model into categories of growth release, suppression, or normal trends. This approach allowed us to identify the occurrence, duration, and severity of forest disturbances based on percentage changes in the growth release or suppression categories of trees. And the effect of climate on tree growth was assessed according to the mean statistics of the growth normal categories. Using common forest disturbances such as defoliating insects and thinning as examples, we validated our method using tree-ring collections from six sites in British Columbia and Quebec, Canada. We found that the GTC method was superior to traditional time-series analysis methods (e.g., Radial Growth Averaging, Boundary Line, Absolute Increase, and Curve Intervention Detection) for detecting past forest disturbances and was able to significantly enhance climate signals. In summary, the GTC method presented in this study introduces a novel statistical approach for accurately distinguishing between forest disturbances and climate signals in tree rings. This is particularly important for understanding forest disturbance regimes under climate change and for developing future disturbance mitigation strategies., 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.)

Radiotherapy showed synergy with immunotherapy, yet the comparative effectiveness of combining immunotherapy (iRT) or chemotherapy (CRT) after platinum therapy failure in advanced non-small cell lung cancer (NSCLC) remains unexplored. We analyzed 163 patients (iRT: n  = 120 vs. CRT: n  = 43) eligible for combination radiotherapy. Before matching, median overall survival (OS) was significantly longer in iRT group (7.79 vs. 4.57 months, hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.41-0.94, p  = 0.024). After 1:2 propensity score matching (PSM) and inverse probability of treatment weighting (IPTW), iRT group showed improved OS, consistent with unmatched analysis (PSM, p  = 0.033 and IPTW, p  = 0.035). Exploratory analysis suggested that PD1 + , central memory PD1 + , and effector memory PD-L1 + CD4 + T cells were strong predictive biomarkers for iRT-treated patients ( P OS  = 0.025, P OS  = 0.002, P OS  = 0.010, respectively). Proliferative CD4 + T cell low was a prognostic ( P OS  = 0.008) and predictive biomarker for iRT ( P OS  < 0.001). Our work revealed iRT was prolonged OS in previously treated advanced NSCLC patients. Additionally, proliferative CD4 + T cell served as prognostic and predictive biomarkers., Competing Interests: M.H. reports collaborations with Merck Serono (advisory role, speakers’ bureau, honoraria, travel expenses, research funding); MSD (advisory role, speakers’ bureau, honoraria, travel expenses, research funding); AstraZeneca (research funding); Novartis (research funding); BMS (advisory role, honoraria, speakers’ bureau); Teva (travel expenses). U.S.G. and P.R.F. received support for presentation activities for Dr Sennewald Medizintechnik GmbH, have received support for investigator initiated clinical studies (IITs) from MSD and AstraZeneca, and contributed at Advisory Boards Meetings of AstraZeneca and Bristol-Myers Squibb. No other declaration of interests were reported., (© 2024 The Authors.)

The structure-tissue exposure/selectivity relationship (STR) aids in lead optimization to improve drug candidate selection and balance clinical dose, efficacy, and toxicity. In this work, butyrocholinesterase (BuChE)-targeted cannabidiol (CBD) carbamates were used to study the STR in correlation with observed efficacy/toxicity. CBD carbamates with similar structures and same molecular target showed similar/different pharmacokinetics. L2 and L4 had almost same plasma exposure, which was not correlated with their exposure in the brain, while tissue exposure/selectivity was correlated with efficacy/safety. Structural modifications of CBD carbamates not only changed drug plasma exposure, but also altered drug tissue exposure/selectivity. The secondary amine of carbamate can be metabolized into CBD, while the tertiary amine is more stable. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters can be used to predict STR. Therefore, STR can alter drug tissue exposure/selectivity in normal tissues, impacting efficacy/toxicity. The drug optimization process should balance the structure-activity relationship (SAR) and STR of drug candidates for improving clinical trials.

This study aims to observe the effects of different doses of Astragali Radix on the expression of glucagon(GLP-1) in se-rum and glucagon receptor(GLP-1R) in cartilage tissue in rats with knee osteoarthritis(KOA), explore the effect of Astragali Radix on the inflammation and apoptosis of KOA by regulating GLP-1/GLP-1R signaling axis, and investigate the mechanism of its action in alleviating KOA. Forty-eight male SD rats were randomly divided into six groups: blank group, model group, low-, medium-, and high-dose Astragali Radix groups(3.125, 6.25, and 12.5 g·kg~(-1)), and glucosamine sulfate group(0.1 g·kg~(-1)). Except for the blank group, rats in other groups were injected with sodium iodoacetate(MIA) into the knee joint to establish KOA models. After successful modeling, the rats were continuously treated for five weeks. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of GLP-1, tumor necrosis factor-alpha(TNF-α), and interleukin-1β(IL-1β) in rat serum. Pathological examination was utilized to observe the pathological changes in knee joint cartilage. The mRNA levels of TNF-α and MMP13 in knee joint cartilage were detected by qRT-PCR, and the protein expression levels of GLP-1R, MMP13, and caspase-8 in knee joint cartilage were detected by Western blot. The expression of GLP-1R and MMP13 in the knee joint was detected by immunohistochemistry. Tunel staining was used to observe the apoptosis of chondrocytes in the knee joint. The above experimental results showed that Astragali Radix may raise the serum levels of GLP-1, reduce serum levels of TNF-α and IL-1, and decrease the relative mRNA expression of TNF-α and MMP13 through the GLP-1/GLP-1R axis. It thus activated GLP-1R, reduced the protein expression of MMP13 and caspase-8 in cartilage, and regulated their related signaling pathways to improve inflammation and apoptosis, so as to protect cartilage and improve KOA.

Background: Clinical and preclinical studies have shown that extra virgin olive oil (EVOO), a major component of the Mediterranean diet, has beneficial effects on brain aging and cognition. Individuals with Down syndrome develop age-dependent cognitive decline and synaptic dysfunction. However, whether EVOO intake is beneficial in Down syndrome is not known., Objective: In this study, by implementing a mouse model of Down syndrome, we aimed to investigate the effect that chronic administration of EVOO has on memory, synaptic function, and neuroinflammation., Methods: Starting at 4 months of age Ts65dn mice were randomized to receive EVOO for 5 months in their diet, after which they were tested for learning and memory impairment. After euthanasia, synaptic function was measured in freshly obtained hippocampal slices, whereas brain tissues were assessed for inflammatory biomarkers., Results: Compared with controls, mice receiving EVOO had a significant improvement in learning and spatial memory. Additionally, field potential recordings showed that treated mice had an improvement in synaptic function. Finally, array analysis showed that EVOO modulated the expression levels of several inflammatory biomarkers., Conclusions: Chronic administration of EVOO to a mouse model of Down syndrome has beneficial effects on memory impairments, synaptic function deficits and neuroinflammation. Our findings provide additional support for the potential therapeutic effects of EVOO also in individuals with Down syndrome., Competing Interests: Declaration of conflicting interestsDomenico Pratico is an Editorial Board Member of this journal but was not involved in the peer-review process nor had access to any information regarding the peer-review.The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

By establishing an in vitro model of D-Gal-induced brain neuronal cell (HT-22) senescence, it was found that TAX treatment significantly increased the activities of SOD and GSH, while decreasing MDA levels in aging HT-22 cells, indicating that TAX effectively restored the total antioxidant capacity and antioxidant enzyme activity of aging HT-22 cells induced by D-Gal, and attenuated cellular oxidative stress injury. In addition, taxifolin could also protect HT-22 cells from aging by up-regulating SIRT1 while reducing the expression of Ac-p53, indicating that TAX may be an active substance that can effectively delay cell aging.

Post-traumatic stress disorder (PTSD) is characterized by hypermnesia of the trauma and a persistent fear response. The molecular mechanisms underlying the retention of traumatic memories remain largely unknown, which hinders the development of more effective treatments. Utilizing auditory fear conditioning, we demonstrate that a redox-dependent dynamic pathway for dendritic spine morphogenesis in the basolateral amygdala (BLA) is crucial for traumatic memory retention. Exposure to a fear-induced event markedly increased the reduction of oxidized filamentous actin (F-actin) and decreased the expression of the molecule interacting with CasL 1 (MICAL1), a methionine-oxidizing enzyme that directly oxidizes and depolymerizes F-actin, leading to cytoskeletal dynamic abnormalities in the BLA, which impairs dendritic spine morphogenesis and contributes to the persistence of fearful memories. Following fear conditioning, overexpression of MICAL1 in the BLA inhibited freezing behavior during fear memory retrieval via reactivating cytokinesis, whereas overexpression of methionine sulfoxide reductase B 1, a key enzyme that reduces oxidized F-actin monomer, increased freezing behavior during retrieval. Notably, intra-BLA injection of semaphorin 3A, an endogenous activator of MICAL1, rapidly disrupted fear memory within a short time window after conditioning. Collectively, our results indicate that redox modulation of actin cytoskeleton in the BLA is functionally linked to fear memory retention and PTSD-like memory., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose of Review: This review aims to synthesize the old issues and current understandings of the etiology of liver cancer, focusing on the diverse causative factors influenced by geographical, socioeconomic, and lifestyle variations across different regions., Recent Findings: We highlight significant geographic disparities in liver cancer risk factors. While hepatitis B and C viruses, aflatoxin exposure, and alcohol consumption remain globally established contributors; metabolic dysfunction-associated steatotic liver disease and metabolic syndromes are increasingly prominent in the West. Chronic HBV and aflatoxin continue to dominate as risk factors in Asia and Africa. Dietary factors, metabolic diseases like diabetes and obesity, genetic predispositions, environmental risk factors and lifestyle choices such as smoking and alcohol use play substantial roles in specific populations. Protective factors like coffee and tea consumption, along with aspirin use, vegetables and fruits have shown potential in reducing HCC risk, although findings vary by population and dietary habits. Liver cancer etiology is influenced by various factors that differ by region. Established risk factors include hepatitis B and C, aflatoxin, and alcohol. Emerging risks, such as metabolic dysfunction-associated steatotic liver disease, are more prevalent in Western countries, while aflatoxin and HBV remains significant in Asia and Africa. Diet, metabolic conditions like diabetes and obesity, genetic predispositions, and lifestyle choices also play crucial roles. Coffee, tea, aspirin, vegetables, and fruits may reduce HCC risk, but effectiveness varies. Future research should integrate epidemiology, genetics, and nutrition, with global cooperation and data sharing essential for effective cancer control strategies., Competing Interests: Declarations. Human and Animal Rights and Informed Consent: Not applicable. Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Four polysaccharides, named FSIP, FSIP-I, FSIP-II and FSIP-III, were isolated from Flos Sophorae Immaturus. Structure characterization revealed that FSIP-I and FSIP-II were types of AG-II-like polysaccharides while FSIP-III featured a RG-II-like structure with high content of GalpA. In vitro experiments showed that FSIPs upregulated HK and PK activities in glycolysis while downregulated G-6-Pase activities in gluconeogenesis. This increased glucose utilization while decreased the glucose synthesis in IR-HepG2 cells, potentially reducing elevated blood sugar levels induced by excess insulin. In terms of antioxidant system, FSIPs decreased the levels of ROS and MDA, and increased the activities of SOD and CAT, enhancing antioxidant capacity to counteract damage caused by insulin resistance in IR-HepG2 cells. To further explore the mechanism, related genes expressions were analyzed. The results found that FSIPs ameliorated insulin resistance via regulating AMPK and IRS-1/PI3K/AKT signal pathways. In the case of AMPK, glucose can be channeled into oxidative (catabolic) pathway, whereas, in the case of IRS-1/PI3K/AKT, glucose can be stored as glycogen (anabolic). This co-modulation could ameliorate insulin resistance by upregulating the glycolysis and repressing the gluconeogenesis in catabolism, and upregulating the glycogen synthesis in anabolism. Additionally, FSIP-III exhibited better anti-insulin resistance activity, attributed to its high content of GalpA., 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.)

At present, as the problem of water shortage and pollution is growing serious, it is particularly important to understand the recycling and treatment of wastewater. Artificial intelligence (AI) technology is characterized by reliable mapping of nonlinear behaviors between input and output of experimental data, and thus single/integrated AI model algorithms for predicting different pollutants or water quality parameters have become a popular method for simulating the process of wastewater treatment. Many AI models have successfully predicted the removal effects of pollutants in different wastewater treatment processes. Therefore, this paper reviews the applications of artificial intelligence technologies such as artificial neural networks (ANN), adaptive network-based fuzzy inference system (ANFIS) and support vector machine (SVM). Meanwhile, this review mainly introduces the effectiveness and limitations of artificial intelligence technology in predicting different pollutants (dyes, heavy metal ions, antibiotics, etc.) and different water quality parameters such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP) in wastewater treatment process, involving single AI model and integrated AI model. Finally, the problems that need further research together with challenges ahead in the application of artificial intelligence models in the field of environment are discussed and presented., 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.)

Background: Endometrial cancer (EC) as one of the most prevalent malignancies in the female reproductive system, usually has a poor diagnosis and unfavorable health effects. Neferine (Nef), derived from the edible and medicinal lotus seed, has been known for its functional activity; however, its anti-cancer mechanism for EC remains elusive., Purpose: We explored the potential anti-cancer effects and underlying molecular mechanisms of Nef on EC., Methods: The cytotoxicity was tested using MTT, and the cell cycle, apoptosis, Ca 2+ levels, and the mitochondrial membrane potential (MMP) were observed through flow cytometry. After Nef treatment, differences in miRNA expression were identified using miRNA-seq data. Furthermore, western blot and immunohistochemistry (IHC) were employed to identify the proteins associated with apoptosis in both mice and cells., Results: Nef treatment led to Ishikawa cell apoptosis and blocked cell proliferation in the G2/M phase. In total, 101 significantly different miRNA (p 〈 0.05 and |logFC| 〉 1) were obtained and subjected to GO and KEGG enrichment analysis, which revealed the Ca 2+ and PI3K/AKT signaling pathways pertaining to apoptosis. Nef treatment significantly changed intracellular Ca 2+ levels and MMP, activating the endoplasmic reticulum stress (ERS) pathway and the expression of key proteins in the mitochondrial pathway. In addition, Nef also inhibited the expression of key proteins in the PI3K/AKT pathway, causing cell apoptosis. Moreover, in mouse tumor tissues, the expression of CHOP, Bcl-2, Caspase 3, Cyto-c, and p-AKT was also consistent with the results in vitro., Conclusion: Nef could block the cell cycle and induce the activation of the mitochondrial apoptotic pathway involving the Ca 2+ -mediated ERS pathway and the PI3K/AKT pathway, thereby inducing apoptosis in EC cells, confirming the potential role of Nef in the prevention and treatment of EC., 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 Author(s). Published by Elsevier GmbH.. All rights reserved.)