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We propose a high efficiency wideband three-fold geometric phase metasurface for versatile operation of transmission and reflection. The transmission coefficient as high as 87 % is achieved in the frequency range of f1 (15.4–15.8 GHz), while equal transmission and reflection are achieved in two frequency bands represented by f2 (14.6–15.2 GHz & 16–17 GHz) with maximum coefficient reaches 49 %. With geometric rotation, the phase shifts of the cross-polarized transmission and co-polarized reflection are six times the rotation angle within the frequency range of 14.6–17 GHz. Furthermore, by elaborately breaking the mirror symmetry while preserving rotational symmetry, interesting features of resonance frequency shift and mode splitting are observed, offering a more fruitful approach for versatile operations. To substantiate the proposed design, a metasurface prototype for vortex beam generation is fabricated and verified by microwave measurement.

Objective: Curcumin, a phenolic compound extracted from turmeric rhizomes, exhibits antitumour effects in preclinical models of tumours. However, its mechanism of action in prostate cancer remains unclear. Exploring the molecular mechanisms of curcumin in prostate cancer based on network pharmacology and molecular docking provides a new theoretical basis for prostate cancer treatment. Method: Using tools such as PharmMapper, SuperPred, TargetNet, and SwissTargetPrediction, we obtained information on curcumin-related targets. We comprehensively collected prostate cancer-related targets from several databases, including GeneCards, CTD, DisGeNET, OMIM, and PharmGKB. Cross-cutting drug-disease targets were then derived by screening using the Venny 2.1.0 tool. Subsequently, we used the DAVID platform to perform in-depth GO and KEGG enrichment analyses of the drug-disease-shared targets. To construct a PPI network map of the cross-targets and screen the 10 core targets, we combined the STRING database and Cytoscape 3.7.2. Molecular docking experiments were performed using AutoDockTools 1.5.7 software. Finally, we used several databases such as GEPIA, HPA, cBioPortal, and TIMER to further analyse the screened core targets in detail. Result: We identified 307 key targets of curcumin in cancer treatment. After GO functional enrichment analysis, we obtained 1119 relevant entries, including 782 biological progression (BP) entries, 112 cellular component (CC) entries, and 225 molecular function (MF) entries. In addition, KEGG pathway enrichment analysis revealed 126 signalling pathways, which were mainly involved in the cancer pathway, such as lipid and atherosclerosis pathway, PI3K-Akt signal pathway, MAPK signal pathway, Ras signal pathways, and chemical carcinogenesis-reactive oxygen species. By applying Cytoscape 3.7.2 software, we identified SRC, PIK3R1, STAT3, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1 as core targets. Molecular docking experiments showed that the binding energies of curcumin to these core targets were all below −1.85 kJ mol−1, which fully demonstrated that curcumin could spontaneously bind to these core targets. Finally, these results were validated at multiple levels, including mRNA expression, protein expression, and immune infiltration. Conclusion: Through in-depth network pharmacology and molecular docking studies, we have found that curcumin may have anticancer potential by upregulating the expression of PIK3R1 and STAT3, and downregulating the binding ability of molecules such as SRC, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1. In addition, curcumin may interfere with the cyclic process of prostate cancer cells by inhibiting key signalling pathways such as the PI3K-Akt signalling pathway, MAPK signalling pathway, and Ras, thereby inhibiting their growth. This study not only reveals the potential molecular mechanism of curcumin in the treatment of prostate cancer but also provides an important theoretical basis for subsequent research.

Objective: Alström Syndrome (AS), caused by biallelic ALMS1 mutations, includes obesity with disproportionately severe insulin resistant diabetes, dyslipidemia, and fatty liver. Prior studies suggest that hyperphagia is accounted for by loss of ALMS1 function in hypothalamic neurones, whereas disproportionate metabolic complications may be due to impaired adipose tissue expandability. We tested this by comparing the metabolic effects of global and mesenchymal stem cell (MSC)-specific Alms1 knockout. Methods: Global Alms1 knockout (KO) mice were generated by crossing floxed Alms1 and CAG-Cre mice. A Pdgfrα-Cre driver was used to abrogate Alms1 function selectively in MSCs and their descendants, including preadipocytes. We combined metabolic phenotyping of global and Pdgfrα+ Alms1-KO mice on a 45% fat diet with measurements of body composition and food intake, and histological analysis of metabolic tissues. Results: Assessed on 45% fat diet to promote adipose expansion, global Alms1 KO caused hyperphagia, obesity, insulin resistance, dyslipidaemia, and fatty liver. Pdgfrα-cre driven KO of Alms1 (MSC KO) recapitulated insulin resistance, fatty liver, and dyslipidaemia in both sexes. Other phenotypes were sexually dimorphic: increased fat mass was only present in female Alms1 MSC KO mice. Hyperphagia was not evident in male Alms1 MSC KO mice, but was found in MSC KO females, despite no neuronal Pdgfrα expression. Conclusions: Mesenchymal deletion of Alms1 recapitulates metabolic features of AS, including fatty liver. This confirms a key role for Alms1 in the adipose lineage, where its loss is sufficient to cause systemic metabolic effects and damage to remote organs. Hyperphagia in females may depend on Alms1 deficiency in oligodendrocyte precursor cells rather than neurones. AS should be regarded as a forme fruste of lipodystrophy.

Cables are indispensable in nuclear power plants for transmitting data measured by various types of detectors, such as self-powered neutron detectors (SPNDs). These cables will generate disturbing signals that must be accurately distinguished and eliminated. Given that the cable current is not very significant, previous research has focused on SPND, with little attention paid to cable evaluation and validation. This paper specifically focuses on the quantitative analysis of cables and proposes a theoretical model to predict cable noise. In this model, the reaction characteristics between irradiated neutrons and cables were discussed thoroughly. Based on the Monte Carlo method, a comprehensive simulation approach of neutron sensitivity was introduced and long-term irradiation experiments in a heavy water reactor (HWR) were designed to verify this model. The theoretical results of this method agree quite well with the experimental measurements, proving that the model is reliable and exhibits excellent accuracy. The experimental data also show that the cable current accounts for approximately 0.2% of the total current at the initial moment, but as the detector gradually depletes, it will contribute more than 2%, making it a non-negligible proportion of the total signal current.

Based on the self-developed high permeability water pressure loading system, the physical and mechanical properties and pore structure evolution under various high permeability water pressures were studied. This study aims to reveal the microscopic damage mechanism of concrete when subjected to high permeability water pressures. The results indicate that the internal water content increases with the rising of water pressure under various high permeability conditions. Furthermore, the higher the water pressure, the greater the reduction in strength, particularly evident in low-strength-grade concrete. High permeability water pressure causes to the expansion of gelatinized pores with small sizes into transition pores. Moreover, there is a concurrent alteration in both pore size and pore number under high permeability water pressure.

Background: Diabetic nephropathy (DN) is a prevalent chronic microvascular complication of diabetes and the leading cause of end-stage renal disease (ESRD). Understanding the progressive etiology of DN is critical for the development of effective health policies and interventions. Recent research indicated that polystyrene microplastics (PS-MPs) contaminate our diets and accumulate in various organs, including the liver, kidneys, and muscles. Methods: In this study, ten-week-old db/db mice and db/m mice were fed. Besides, db/db mice were divided into two groups: PS-MPs group (oral administration of 0.5 µm PS-MPs) and an H2O group, and they were fed for three months. A type II diabetes model was established using db/db mice to investigate the effects of PS-MPs on body weight, blood glucose level, renal function, and renal fibrosis. Results: The results demonstrated that PS-MPs significantly exacerbated various biochemical indicators of renal tissue damage, including fasting blood glucose, serum creatinine, blood urea nitrogen, and blood uric acid. Additionally, PS-MPs worsened the pathological alterations and degree of fibrosis in renal tissue. An increased oxidative stress state and elevated levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) were identified. Furthermore, PS-MPs significantly enhanced renal fibrosis by inhibiting the transition from epithelial cells to mesenchymal cells, specifically through the inhibition of the TGF-β/Smad signaling pathway. The expression levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and cleaved Caspase-1, which are inflammasome proteins, were significantly elevated in the PS-MPs group. Conclusion: The findings suggested that PS-MPs could aggravate kidney injury and renal fibrosis in db/db mice by promoting NLRP3/Caspase-1 and TGF-β1/Smads signaling pathways. These findings had implications for elucidating the role of PS-MPs in DN progression, underscoring the necessity for additional research and public health interventions.

Microbubble’s mass transfer under external acoustic excitation holds immense potential across various technological fields. However, the current state of acoustic technology faces limitations due to inadequate control over bubble size in liquids under external excitation. Here, we conducted numerical investigations of the mass transfer behavior of microbubbles in liquids under multifrequency acoustic excitations with different frequencies (in the MHz range), pressure amplitudes (in the range of several atmospheric pressures), and amplitude ratios. We identified various pressure threshold regions for the growth of gas bubbles (radii range from a few microns to tens of microns) and observed common intersections between single and multifrequency excitations that enable effective control of the growth intervals and final size of bubbles by adjusting the ratio of pressure amplitude and frequency value. Allocating power to the lower frequency component of multifrequency acoustic excitation is recommended to facilitate mass transfer or diffusion, as small-frequency acoustic excitation has a more significant effect than the higher frequency in the growth region. Our study provides a better understanding of the dynamics of bubbles under complex excitations and has practical implications for developing methods to control and promote bubble-related processes.

With the frequent occurrence of worldwide extreme climate events, human-induced ecosystem degradation has seriously threatened the realization of the Sustainable Development Goals (SDGs), especially in arid ecologically fragile areas. Macro-scale ecological quality (EQ) monitoring and exploration of its driving mechanisms have become research hotspots. However, this research field still lacks a method framework with strong comparability, adaptability and transferability, which significantly restricts the applicability of research results. In this study, a method framework for exploring spatial and temporal changes in EQ and their driving mechanisms based on text summarization and information extraction is constructed. Taking Central Asia as a typical case, this study outlines its EQ driving paths, explores the influencing mechanisms of representative drivers, and verifies the effectiveness of this method framework based on the comparison of the spatial and temporal evolution of EQ at multiple scales. The results indicate that the overall EQ in Central Asia exhibited a slight inverted U-shaped trend, with its driving paths falling into five categories: urban expansion, agricultural development, resource extraction, climate change, and ecological protection. The fragmentation of areas with high EQ is the main landscape characteristic in Central Asia. Furthermore, land use intensity and agricultural water use efficiency are significant factors in Central Asia's EQ evolution. Over time, the interaction between anthropogenic and natural factors has played an essential role in EQ evolution in Central Asia, with interactions between altitude, climate aridity, agricultural water use efficiency, and land use intensity gradually intensifying. This study has an implication for the construction of method framework for EQ-related study in ecologically fragile areas at the macro scale.

The use of oral agents that can modify the gut microbiota (GM) could be a novel preventative or therapeutic option for Parkinson’s disease (PD). Maslinic acid (MA), a pentacyclic triterpene acid with GM-dependent biological activities when it is taken orally, has not yet been reported to be effective against PD. The present study found both low and high dose MA treatment significantly prevented dopaminergic neuronal loss in a classical chronic PD mouse model by ameliorating motor functions and improving tyrosine hydroxylase expressions in the substantia nigra pars compacta (SNpc) and increasing dopamine and its metabolite homovanillic acid levels in the striatum. However, the effects of MA in PD mice were not dose-responsive, since similar beneficial effects for low and high doses of MA were observed. Further mechanism studies indicated that low dose MA administration favored probiotic bacterial growth in PD mice, which helped to increase striatal serotonin, 5-hydroxyindole acetic acid, and γ-aminobutyric acid levels. High dose MA treatment did not influence GM composition in PD mice but significantly inhibited neuroinflammation as indicated by reduced levels of tumor necrosis factor alpha and interleukin 1β in the SNpc; moreover, these effects were mainly mediated by microbially-derived acetic acid in the colon. In conclusion, oral MA at different doses protected against PD via distinct mechanisms related to GM. Nevertheless, our study lacked in-depth investigations of the underlying mechanisms involved; future studies will be designed to further delineate the signaling pathways involved in the interactive actions between different doses of MA and GM.

The recrystallization behavior of extruded Mg–Zn–Mn alloys was systematically investigated under different aging treatment prior to extrusion. Electron backscattered diffraction analysis was used to explore the recrystallization mechanism and corresponding effects on the basal texture of alloys during extrusion. The results show that the primary coarse particles can effectively promote recrystallization nucleation. Moreover, the precipitation of nanoscale particles during the aging process play a role in pinning the grain boundaries. Therefore, after peak-aged treatment (16 h), the extruded Mg alloy obtains uniform and fine microstructure, showing good mechanical properties: the tensile yield strength, tensile strength, elongation, compressive yield strength, and tension-compression yield asymmetry were 298 MPa, 363 MPa, 26%, 260 MPa, and 0.87, respectively.

Previous reports have observed a consistent J-shaped relationship between cardiac events and diastolic blood pressure (DBP). However, the EPHESUS study clearly showed that myocardial reperfusion abolished the J-shaped association, suggesting a different association pattern after revascularization. Therefore, in this study, we investigated the different patterns in which DBP affects cardiovascular risk in non ST-segment elevation myocardial infarction (NSTEMI) patients after revascularization, which may benefit the risk stratification for NSTEMI patients. We obtained the NSTEMI database from the Dryad data repository and analyzed the association between preprocedural DBP and long-term major adverse cardiovascular events (MACEs) in 1486 patients with NSTEMI following percutaneous coronary intervention (PCI). Multivariate regression models were used to assess the impact of DBP on outcomes in an adjusted fashion according to DBP tertiles. The p value for the trend was calculated using linear regression. When examined as a continuous variable, a multivariate regression analysis was repeated. Pattern stability was verified by interaction and stratified analyses. The median (interquartile range) age of the patients was 61.00 (53.00–68.00) years, and 63.32% were male. Cardiac death showed a graded increase as the DBP tertile increased (p for trend = 0.0369). When examined as a continuous variable, a 1 mmHg increase in DBP level was associated with an 18% higher risk of long-term cardiac death (95% CI: 1.01–1.36, p = 0.0311) and a 2% higher risk of long-term all-cause death (95% CI: 1.01–1.04; p = 0.0178). The association pattern remained stable when stratified by sex, age, diabetes, hypertension, and smoking status. An association between low DBP and higher cardiovascular risk was not observed in our study. We showed that higher preprocedural DBP increased the risk of long-term cardiac death and all-cause death in patients with NSTEMI following PCI.

Background: The COVID-19 outbreak in late December 2019 has quickly emerged into pandemic in 2020. We aimed to describe the epidemiology and clinical characteristics of hospitalized COVID-19 patients, and to investigate the potential risk factors for COVID-19 severity. Method: 1663 hospitalized patients with laboratory-confirmed diagnosed COVID-19 from Tongji Hospital between January 14, 2020, and February 28, 2020 were included in the present study. Demographic information, exposure history, medical history, comorbidities, signs and symptoms, chest computed tomography (CT) scanning, severity of COVID-19 and laboratory findings on admission were collected from electronic medical records. Multivariable logistic regression was used to explore the association between potential risk factors with COVID-19 severity. Results: In the present study, the majority (79%) of 1663 COVID-19 patients were aged over 50 years old. A total of 2.8% were medical staff, and an exposure history of Huanan seafood market was document in 0.7%, and 7.4% were family infection. Fever (85.8%), cough (36.0%), fatigue (23.6%) and chest tightness (11.9%) were the most common symptoms in COVID-19 patients. As of February 28, 2020, of the 1663 patients included in this study, 26.0% were discharged, 10.2% were died, and 63.8% remained hospitalized. More than 1/3 of the patients had at least one comorbidity. Most (99.8%) patients had abnormal results Chest CT, and the most common manifestations of chest CT were local patchy shadowing (70.7%) and ground-glass opacity (44.8%). On admission, lymphocytopenia was present in 51.1% of the patients, mononucleosis in 26.6%, and erythrocytopenia in 61.3%. Most of the patients had increased levels of C-reactive protein (80.4%) and D-dimer (64.4%). Compared with non-severe patients, severe patients had more obvious abnormal laboratory results related to inflammation, coagulation disorders, liver and kidney damage (all P < 0.05). Older age (OR = 2.37, 95% CI: 1.47–3.83), leukocytosis (OR = 2.37, 95% CI: 1.47–3.83), and increased creatine kinase (OR = 2.37, 95% CI: 1.47–3.83) on admission were significantly associated with COVID-19 severity. Conclusion: Timely medical treatment and clear diagnosis after the onset might be beneficial to control the condition of COVID-19. Severe patients were more likely to be to be elder, and tended to have higher proportion of comorbidities and more prominent laboratory abnormalities. Older age, leukocytosis, and increased creatine kinase might help clinicians to identify severe patients with COVID-19.

Objective: Increased deposition of the extracellular matrix (ECM) in adipose tissue (AT) during obesity contributes to insulin resistance. The integrin receptors transmit changes in the extracellular environment causing corresponding intracellular adaptations. Integrin-linked kinase (ILK), an adaptor protein, is a central hub for intracellular signaling of integrins. This study determined the role of ILK in adipose function and insulin resistance. Methods: The pathogenic role of ILK in obesity and insulin resistance was studied in human adipose tissue and adipocyte-specific ILK-deficient mice (ILKlox/loxAdCre). ILKlox/loxAdCre mice together with wild-type littermates (ILKlox/lox) were fed a chow diet or 60% high-fat (HF) diet for 16 weeks. In vivo insulin sensitivity was determined by hyperinsulinemic-euglycemic clamps. Results: AT ILK expression was increased by HF diet feeding in mice and increased in visceral fat of morbidly obese humans. The HF-fed ILKlox/loxAdCre mice displayed reduced fat mass and improved glucose tolerance relative to the HF-fed ILKlox/lox mice. During a hyperinsulinemic-euglycemic clamp, the HF-fed ILKlox/loxAdCre mice exhibited partially improved insulin resistance in AT. Lipolysis was suppressed to a greater extent by insulin and glucose uptake in brown AT (BAT) increased. Increased inhibition of lipolysis may have been attributed to increased vascularization in white AT, while increased glucose uptake in BAT was associated with increased Akt phosphorylation and P38/JNK dephosphorylation. Notably, AT insulin sensitivity in lean mice was not affected by ILK deletion. Moreover, reduced fat mass in the HF-fed ILKlox/loxAdCre mice may have been attributed to decreased free fatty acid uptake into adipocytes via the downregulation of CD36 gene expression. Consistent with the results in the mice, knockdown and knockout of ILK in 3T3-L1 cells decreased lipid accumulation and CD36 gene expression during adipogenesis. Conclusions: These data show that adipocyte ILK is important for regulating HF diet-mediated insulin resistance in AT in a manner consistent with AT function.

Background: Since the outbreak of coronavirus disease (COVID-19) in Wuhan in December 2019, by March 10, 2020, a total of 80,932 confirmed cases have been reported in China. Two consecutively negative RT-PCR test results in respiratory tract specimens is required for the evaluation of discharge from hospital, and oropharyngeal swabs were the most common sample. However, false negative results occurred in the late stage of hospitalization, and avoiding false negative result is critical essential. Methods: We reviewed the medical record of 353 patients who received tests with both specimens simultaneously, and compared the performance between nasopharyngeal and oropharyngeal swabs. Results: Of the 353 patients (outpatients, 192; inpatients, 161) studied, the median age was 54 years, and 177 (50.1%) were women. Higher positive rate (positive tests/total tests) was observed in nasopharyngeal swabs than oropharyngeal swabs, especially in inpatients. Nasopharyngeal swabs from inpatients showed higher positive rate than outpatients. Nasopharyngeal swabs from male showed higher positive rate than female, especially in outpatients. Detection with both specimens slightly increased the positive rate than nasopharyngeal swab only. Moreover, the consistency between from nasopharyngeal and oropharyngeal swabs were poor (Kappa = 0.308). Conclusion: In conclusion, our study suggests that nasopharyngeal swabs may be more suitable than oropharyngeal swab at this stage of COVID-19 outbreak.

Background: Blood-based biomarker such as circulating tumor DNA (ctDNA) has emerged as a promising tool for assessment of response to immunotherapy in solid tumors; But in hematological malignances, evidences are still lacking to support its clinical utility. In current study the feasibility of ctDNA for prediction and monitoring of response to anti-PD-1 therapy in Chinese patients with relapsed or refractory classical Hodgkin lymphoma (r/r cHL) was assessed. Methods: A total of 192 plasma samples from 75 patients with r/r cHL were collected at baseline and upon therapeutic evaluation. ctDNA were sequenced by targeting panels capturing frequently mutated genes in cHL and other hematological malignancies and then quantified. Analysis on: 1) Gene mutation profile and association of the gene mutations with progression-free survival; 2) Association of pre- and post-treatment ctDNA variant allelic frequencies with clinical outcome; (3) Correlation of the mutated genes with treatment resistance; were performed. Findings: Somatic mutations were detected in 50 out of 61 patients by ctDNA genotyping. The mutations of CHD8 was significantly higher in patients with PFS ≥ 12 months. Baseline ctDNA was significantly higher in responders and a decrease of ctDNA ≥ 40% from baseline indicated superior clinical outcome. Strong agreement between ctDNA dynamic and radiographic response change during therapy was observed in majority of the patients. Furthermore, the mutations of B2M, TNFRSF14 and KDM2B were found to be associated with acquired resistance. Interpretation: ctDNA could be an informative biomarker for anti-PD-1 immunotherapy in r/r cHL. Funding: This work was supported by Innovent Biologics, Eli Lilly and Companyhttps://doi.org/10.13039/501100002852, China National New Drug Innovation Program (2014ZX09201041-001 and 2017ZX09304015), Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001) and National Key Scientific Program Precision Medicine Research Fund of China (2017YFC0909801). The funders had no role in study design, data collection, data analysis, interpretation or writing. Keywords: Circulating tumor DNA, Immunotherapy, anti-PD-1, Biomarker, Classical hodgkin lymphoma, Sintilimab

Proteins and bioactive peptides in avian egg whites exert anti-inflammatory activity. Here, we aimed to evaluate the anti-inflammatory effect of ovotransferrin (OVT) and its di-peptides by simulated peptide-cut using an in vitro model of TNF-α-induced inflammation in Caco-2 cells. Results showed that co-treatment with OVT can’t inhibit the IL-8 secretion in TNF-α-induced Caco-2 cells. Among 18 di-peptides derived from OVT based on simulated peptide-cut, CR, FL, HC, LL and MK markedly decreased IL-8 secretion. Furthermore, these five di-peptides were able to significantly inhibited gene expression of pro-inflammatory cytokines, including TNF-α, IL-8, IL-6, IL-1β, and IL-12, and promoted gene expression of anti-inflammatory cytokines, such as IL-10, in Caco-2 cells. CR, FL, HC, LL and MK inhibited the phosphorylation of inhibitor of κB (IκB). Meanwhile, CR and HC decreased the phosphorylation of p-JNK and p-p-38. These results indicated that CR and HC inhibited the NF-κB and MAPK signaling pathway in TNF-α-induced Caco-2 cells. Nevertheless, LL, FL and MK exerted their anti-inflammatory activity via MAPK signaling pathway. The study suggested that CR, FL, HC, LL and MK have the potential to attenuate intestinal inflammation.

Preserved eggs are widely used as an anti-inflammatory food in dietary therapy. The objective of the present study is to evaluate the effects of simulated gastrointestinal digest from preserved egg white (SGD-PEW) on an in vitro model of tumor necrosis factor (TNF)-α-induced inflammation in Caco-2 cells and a mouse model of dextran sodium sulfate-induced colitis. Results showed that SGD-PEW inhibited the secretion of interleukin (IL)-8, reduced TNF-α-induced expression of genes, including TNF-α, IL-6, IL-1β, interferon gamma (IFN-γ), and IL-17, which are involved in inflammation, and upregulated the expression of the anti-inflammatory cytokines, such as IL-10, in Caco-2 cells. In mice, the treatment of SGD-PEW significantly reduced the clinical signs, weight loss, shortening of the colon and histological scores and downregulated the gene expression of pro-inflammatory cytokines, including TNF-α, IL-6, IL-1β, IFN-γ, and IL-17, in the colon. Thus, SGD-PEW may be a novel preventative food for the treatment of intestinal inflammation.

In this study, we developed a novel covalent organic framework (COF) material, termed RuCOFs, specifically designed and synthesized for electrochemiluminescence (ECL) sensor applications. RuCOFs are based on the classic ECL emitter Ru(dcbpy) 3 2+ , ingeniously integrating 4,4',4''-(1,3,5-triazine-2,4,6-triyl) triphenylamine (TAPT) with [2,2'-bipyridine]-5,5'-diamine (BPYDA), forming a structure with a high specific surface area. This configuration not only significantly enhances the stability of the ECL signal but also provides ideal N,N'-bipyridine chelating sites for efficient metal ion recognition. Utilizing Ru(dcbpy) 3 2+ -functionalized COF (RuCOFs), a novel dual-function ECL sensor was developed, achieving high sensitivity and selectivity in detecting mercury (Hg 2 ⁺) and zinc (Zn 2 ⁺) ions. Experimental results indicate that Hg 2 ⁺ significantly quenches the ECL signal, while Zn 2 ⁺ markedly enhances it, with detection limits of 4.71 nM for Hg 2 ⁺ and 6.57 nM for Zn 2 ⁺ across a wide linear response range from 1 μM to 1 nM. This research not only demonstrates the significant advantages of COF-based ECL sensing platforms in tracking environmental metal ions but also opens new possibilities for environmental monitoring., 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.)

Study Objective: This study aims to evaluate the impact of Supreme™ laryngeal masks versus endotracheal tubes on atelectasis during general anesthesia using lung ultrasound (LUS), and provide evidence for respiratory management., Design: A single-center, double-blind, randomized controlled trial was conducted., Setting: The study was conducted in both the operating room and the post-anesthesia care unit, with follow-up assessments performed in the ward., Patients: Enrollment included 180 cases undergoing non-laparoscopic surgeries in gynecology, urology, and orthopedic limb surgeries., Interventions: Patients were randomly assigned 1:1 to the endotracheal intubation or laryngeal mask group., Measurements: LUS scores were recorded across 12 lung regions at baseline, 15 min after airway establishment, at the end of surgery, and 30 min following airway removal. Outcome measures encompassed the oxygenation index, dynamic lung compliance, incidence of postoperative pulmonary complications, throat pain, and other postoperative complications assessed at 24 and 48 h postoperatively. The primary outcome focused on the LUS score in all 12 lung regions at 15 min after airway establishment., Main Results: Intention-to-treat analysis of 177 subjects revealed endotracheal intubation led to significantly higher LUS scores at 15 min {P < 0.001, mean difference 4.15 ± 0.60, 95% CI [2.97, 5.33]}, end of surgery (P < 0.001, mean difference 3.37 ± 0.68, 95% CI [2.02, 4.72]), and 30 min post-removal (P < 0.001, mean difference 2.63 ± 0.48, 95% CI [1.68, 3.58]). No major complications occurred in the two groups., Conclusions: Compared to endotracheal intubation, laryngeal masks effectively reduce atelectasis formation and progression in gynecological, urological non-laparoscopic, and orthopedic limb surgeries. However, caution is warranted when generalizing these findings to surgeries with a higher risk of laryngeal mask leakage or obese patients. Additionally, the efficacy of laryngeal masks in reducing postoperative atelectasis remains uncertain when comprehensive monitoring of muscle relaxation and reversal therapy is employed., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Neuroinflammation plays a crucial role in the repair of spinal cord injury (SCI), with microglia, pivotal in neuroinflammation, driving either degeneration or recovery in this pathological process. Recently, plasma-derived exosomes (denoted Exos) have presented a high capacity for promoting functional recovery of SCI through the anti-inflammatory effects, and pretreated exosomes are associated with better outcomes. Thus, we aimed to explore whether melatonin-pretreated plasma-derived exosomes (denoted MExo) could exert superior effects on SCI, and attempted to elucidate the potential mechanisms., Methods: Electron microscopy, nanoparticle tracking analysis, and western blot were applied to delineate the distinctions between Exos and MExos. To assess their therapeutic potentials, we established a contusion SCI rat model, complemented by a battery of in vitro experiments comparing both groups. Subsequently, a miRNA microarray analysis was conducted, followed by a series of rescue experiments to elucidate the specific role of miRNAs in MExos. To further delve into the molecular mechanisms involved, we employed western blot analysis and the luciferase reporter gene assay., Results: Melatonin promoted the release of exosome from plasma, concurrently amplifying their anti-inflammatory properties. Furthermore, it was discerned that MExos facilitated a transition in microglia polarization from M1 to M2 phenotype, a phenomenon more pronounced than that observed with Exos. In an endeavor to elucidate this variance, we scrutinized miRNAs exhibiting elevated expression levels in MExos, pinpointing miR-138-5p as a pivotal element in this dynamic. Following this, an in-depth investigation into the role of miR-138-5p was undertaken, which uncovered its efficacy in driving phenotypic alterations within microglia. The analysis of downstream genes targeted by miR-138-5p revealed that it exerted a negative regulatory influence on SOX4, which was found to obstruct the generation of M2-type microglia and the secretion of anti-inflammatory cytokines, thereby partially elucidating the mechanism behind miR-138-5p's regulation of microglia polarization., Conclusions: We innovatively observed that melatonin enhanced the anti-inflammatory function of Exos, which further decreased the expression of SOX4 by delivering miR-138-5p. This inhibition promoted the conversion of M1 microglia to M2 microglia, thus offering a viable option for the treatment of SCI., The Translational Potential of This Article: This study highlights that melatonin enhances the anti-inflammatory function of Exos through delivery of miR-138-5p. Activation of miR-138-5p/SOX4 axis by engineered melatonin-pretreated plasma exosomes may be a potential target for SCI treatment., Competing Interests: The authors declare no confict of interest., (© 2024 The Authors.)

The phase separation of N 6 -methyladenosine (m 6 A) binding protein YTHDF2 plays a vital role in arsenic-induced skin damage, and YTHDF2 can bind to m 6 A-methylated mRNA of tumor suppressor PTEN. However, whether and how YTHDF2 phase separation regulates PTEN involved in arsenic-induced malignant transformation of keratinocytes remains blank. Here, we established arsenite-induced transformation models with stable expression of wild-type YTHDF2 or mutant YTHDF2 protein in vitro and in vivo. We found that the YTHDF2 protein underwent phase separation during arsenite-induced malignant transformation of keratinocytes, and YTHDF2 phase separation promoted the malignant phenotype of keratinocytes. Mechanically, YTHDF2 phase separation reduced PTEN protein levels, which in turn activated the pro-survival AKT signal. The binding of YTHDF2 to multiple m 6 A sites on PTEN mRNA drove YTHDF2 phase separation, inhibiting PTEN translation initiation and thus reducing PTEN protein levels. YTHDF2 phase separation recruited translation-initiation-factor kinase EIF2AK1 to phosphorylate eIF2α, thereby inhibiting translation initiation of poly-m 6 A-methylated PTEN mRNA. Furthermore, arsenite-induced oxidative stress triggered YTHDF2 phase separation by increasing m 6 A levels of PTEN mRNA. Our results demonstrated that YTHDF2 phase separation promotes arsenite-induced malignant transformation by inhibiting PTEN translation in a poly-m 6 A-dependent manner. This study sheds light on arsenic carcinogenicity from the novel aspect of m 6 A-mediated YTHDF2 phase separation., 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: The associations between prenatal antibiotics exposure and attention-deficit/hyperactivity disorder (ADHD) in preschoolers, and the role of maternal vitamin D in these associations, remain to be explored., Objectives: To evaluate the relationships between multiple maternal urinary antibiotics levels and preschoolers' ADHD symptoms, and to identify the potential modifying effects of maternal vitamin D., Methods: Based on a prospective birth cohort, the present study included 2033 motherchild pairs. Maternal urine and serum samples were collected during all three trimesters to measure the urinary concentrations of 43 antibiotics (including two metabolites) and the serum vitamin D levels. The ADHD symptoms of preschoolers were assessed using the Diagnostic and Statistical Manual-oriented ADHD problems scale in the Achenbach Child Behavior Checklist. Multiple informant models in the form of logistic regression were conducted to investigate the associations between prenatal antibiotics exposure and preschooler ADHD symptoms, and these associations were stratified by child sex and maternal vitamin D status., Results: Compared with the lowest tertile concentrations, maternal exposure to the middle tertile concentrations of doxycycline and human antibiotics/preferred as human antibiotics (HAs/PHAs), and the highest tertile concentrations of doxycycline during the first trimester were associated with an increased risk of ADHD symptoms in children. An increased risk of ADHD symptoms was observed in girls exposed to the highest tertile levels of sulfamethazine during the second trimester. Furthermore, pregnant women with vitamin D deficiency have a greater risk of ADHD symptoms in their offspring after exposure to doxycycline in the first trimester., Conclusions: Maternal exposure to doxycycline and HAs/PHAs during the first trimester increases the risk of ADHD symptoms in preschoolers. Mid-pregnancy sulfamethazine exposure increases the risk of ADHD symptoms in girls. Maternal vitamin D deficiency during pregnancy may exacerbate the adverse effects of doxycycline exposure on ADHD symptoms., 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.)

Acetylcholinesterase (AChE), an essential neurotransmitter hydrolase, is targeted by organophosphorus and carbamate pesticides, and its number varies among species. In Aleuroglyphus ovatus, a pest mite that endangers health and economy, Aoace1 and Aoace2 have been identified encoding 590 and 460 amino acids, respectively, with characteristic structures, including catalytic triads, oxyanion holes, acyl pockets, peripheral anion, and catalytic anion sites. Phylogenetic analysis reveals distinct clusters for each gene. Expression patterns indicate that Aoace1 predominates in eggs, while Aoace2 is substantially expressed in adults. Experiments on the response of the Aoace genes to phoxim and natural pyrethrins showed that except for the Aoace2 gene responded to natural pyrethrins, all the experimental groups showed a significant increase at LC 30 agent concentration. RNA interference with Aoace1 and Aoace2 significantly reduced AChE activity, and increased mortality with LC 30 concentrations of phoxim by 15.8 % and 31.5 %, while increased mortality with LC 30 concentrations of natural pyrethrins by 43.4 % and 40.4 %, respectively. Knockdown of ace gene significantly decreased fecundity and vitellogenin gene expression. These findings suggest that Aoace1 and Aoace2 are involved in cholinergic and non-cholinergic functions, with Aoace2 being more influential, offering new insights for A. ovatus control 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.)

Background: Maternal exposure to multiple antibiotics exposure during pregnancy has attracted extensive attention, but biomonitoring studies linking prenatal antibiotic exposure to emotional and behavioural problems in children are limited., Methods: A total of 2475 pregnant women from the Ma'anshan Birth Cohort were included, and the Strengths and Difficulties Questionnaire was completed when their children turned four years of age. The levels of 41 maternal urinary antibiotics and two metabolites were measured during the first, second and third trimesters. Generalized estimating equations and binary logistic regression models were applied to analyse the associations between maternal antibiotic exposure and emotional and behavioural problems in children and to determine the sensitive period, respectively. A quantile-based g-computation (QGC) approach was employed to examine the combined effects of multiple antibiotics on emotional and behavioural problems in children., Results: Overall, florfenicol and preferred-as-veterinary antibiotic (PVA) exposure during pregnancy increased the risk of emotional problems in children, and ofloxacin exposure increased the risk of hyperactivity-inattention. Maternal exposure to trimethoprime, ciprofloxacin, florfenicol, other antibiotics and PVA exposure during the first trimester was positively associated with emotional problems in children. Second-trimester trimethoprime concentrations and third-trimester ciprofloxacin concentrations were positively associated with hyperactivity-inattention. Third-trimester veterinary antibiotic (VA) exposure was negatively associated with hyperactivity-inattention, and second-trimester VA and PVA exposure was negatively associated with peer problems. The QGC model revealed that mixed antibiotic exposure in the first trimester exacerbated the risk of childhood emotional problems (the contribution of ciprofloxacin is prominent), and mixed antibiotic exposure in the second trimester increased the risk of hyperactivity-inattention (the contribution of trimethoprime is prominent)., Conclusion: Maternal mixed antibiotic exposure during the first and second trimesters increases the risk of emotional problems and hyperactivity-inattention in children at four years of age., 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.)

Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx. Palate, lung, and nasal epithelium clone (PLUNC) has been identified as an early secreted protein that is specifically expressed in the nasopharynx. The aim of this study was to determine the role and mechanism of PLUNC in NPC. We used mRNA sequencing (seq) combined with ribosome-nascent chain complex (RNC)-seq to determine the biological role of PLUNC. The expression of epithelial-to-mesenchymal transition (EMT)-related molecules was detected by western blotting. Then, cell migration and invasion were detected by wound healing and Transwell chamber assays. NPC cells were injected into the tail vein of nude mice to explore the biological role of PLUNC in vivo. The sequencing results showed that PLUNC inhibited the progression of NPC and its expression was correlated with that of NOD-like receptors. Experiments confirmed that PLUNC inhibited the invasion and metastasis of NPC cells by promoting the ubiquitination degradation of NLRP3. PLUNC overexpression in combination with the treatment by MCC950, an inhibitor of NLRP3 inflammasome activation, was most effective in inhibiting NPC invasion and metastasis. In vivo experiments also confirmed that the combination of PLUNC overexpression and MCC950 treatment effectively inhibited the lung metastasis of NPC cells. In summary, our research suggested that PLUNC inhibited the invasion and metastasis of NPC by inhibiting NLRP3 inflammasome activation, and targeting the PLUNC-NLRP3 inflammasome axis could provide a new strategy for the diagnosis and treatment of NPC patients., 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.)

As an adjunct therapy, metformin enhances the efficacy of conventional antidepressant medications. However, its mode of action remains unclear. Here, metformin was found to ameliorate depression-like behaviors in mice exposed to chronic restraint stress (CRS) by normalizing the dysbiotic gut microbiome. Fecal transplants from metformin-treated mice ameliorated depressive behaviors in stressed mice. Microbiome profiling revealed that Akkermansia muciniphila (A. muciniphila), in particular, was markedly increased in the gut by metformin and that oral administration of this species alone was sufficient to reverse CRS-induced depressive behaviors and normalize aberrant stress-induced 5-hydroxytryptamine (5-HT) metabolism in the brain and gut. Untargeted metabolomic profiling further identified the bile acid metabolites taurocholate and deoxycholic acid as direct A. muciniphila-derived molecules that are, individually, sufficient to rescue the CRS-induced impaired 5-HT metabolism and depression-like behaviors. Thus, we report metformin reprograms 5-HT metabolism via microbiome-brain interactions to mitigate depressive syndromes, providing novel insights into gut microbiota-derived bile acids as potential therapeutic candidates for depressive mood disorders from bench to bedside., 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.)

The impact of cadmium (Cd) toxicity on fish liver injury has received much attention in recent years. Currently, autophagy, apoptosis and endoplasmic reticulum stress were reported in Cd exposed fish liver, and if there are other mechanisms (such as ferroptosis) and relevant signaling pathways involved in fish remains unknown. An experiment was conducted to investigate Cd toxicity in Channa argus (Cantor, 1842) exposed to 0, 1.0, and 2.0 mg Cd/L of water for 96 h. Cd disrupted the structure of mitochondria in the liver. Besides, Cd induced ferroptosis by significantly increasing the level of Fe 2+ , ROS, MDA and significantly decreasing the level of Ferritin, GSH, GSH-Px, GPX4, GST and SOD (p < 0.05 in all cases). In addition, the mRNA expression of ferroptosis related genes, gpx4 and slc7a11, were significantly downregulated by Cd. Moreover, Cd exposure significantly inhibited the Nrf2/Keap1 signaling pathway, one of the pathways involved in ferroptosis, by upregulating the mRNA levels of keap1a and keap1b, and downregulating the mRNA levels of nrf2 and its target genes (ho-1, nqo1 and cat). Cd exposure also caused extensive accumulation of vacuoles and lipid droplets in liver, as well as an increase in triglyceride content. Cd significantly affected lipid metabolism related enzyme activity and gene expression, which were also regulated by Nrf2/Keap1 signaling pathway. In summary, these results indicate that ferroptosis is a mechanism in waterborne Cd exposed fish liver injury via the Nrf2/Keap1 signaling pathway and the Cd induced hepatic steatosis is also modulated by Nrf2/Keap1 pathway at the whole-body level in fish. These findings provide new insights into the fish liver injury and molecular basis of Cd toxicity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lei Pan and Dong Liu reports were provided by Department of Science and Technology of Hubei 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 The Authors. Published by Elsevier Inc. All rights reserved.)

In the natural environment, a symphony of environmental factors including sunlight exposure, current fluctuations, sodium chloride concentrations, and sediment dynamics intertwine, potentially magnifying the impacts on the aging process of disposable face masks (DFMs), thus escalating environmental risks. Employing Regular Two-Level Factorial Design, the study scrutinized interactive impacts of ultraviolet radiation, sand abrasion, acetic acid exposure, sodium chloride levels, and mechanical agitation on mask aging. Aging mechanisms and environmental risks linked with DFMs were elucidated through two-dimensional correlation analyses and risk index method. Following a simulated aging duration of three months, a single mask exhibited the propensity to release a substantial quantity of microplastics, ranging from 38,800 ± 360 to 938,400 ± 529 particles, and heavy metals, with concentrations from 0.06 ± 0.02 μg/g (Pb) to 29.01 ± 1.83 μg/g (Zn). Besides, specific contaminants such as zinc ions (24.24 μg/g), chromium (VI) (4.20 μg/g), thallium (I) (0.92 μg/g), tetracycline (0.51 μg/g), and acenaphthene (1.73 μg/g) can be adsorbed significantly by aged masks. The study elucidates pivotal role of interactions between ultraviolet radiation and acetic acid exposure in exacerbating the environmental risks associated with masks, while emphasizing the pronounced influence of many other interactions. The research provides a comprehensive understanding of the intricate aging processes and ensuing environmental risks posed by DFMs, offering valuable insights essential for developing sustainable management strategies in aquatic ecosystems., 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: The ONCO DVT study (Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis) revealed superiority of 12-month relative to 3-month edoxaban treatment for the thrombotic risk in cancer-associated isolated distal deep vein thrombosis. However, it is unknown whether the superiority could be common in different modified Ottawa score subgroups., Objectives: To identify more preferable candidates for extended anticoagulation in patients with cancer-associated isolated distal deep vein thrombosis using the modified Ottawa score., Methods: In this post-hoc subgroup analysis of the ONCO DVT study, we stratified 601 patients into the low (≤-1, N = 126), intermediate (0, N = 323), and high (≥1, N = 152) modified Ottawa score subgroups and compared clinical outcomes between the 12-month and 3-month edoxaban treatment groups., Results: The cumulative incidence of symptomatic recurrent venous thromboembolism or venous thromboembolism-related death was not different between the 12-month and 3-month edoxaban treatment groups in the low score subgroup (0.0% vs 2.2%), whereas it was lower in the 12-month than in the 3-month edoxaban treatment group in the intermediate (0.8% vs 7.6%) and high (3.1% vs 15.6%) score subgroups. There were no significant differences in the cumulative incidences of the major bleeding between the 12-month and 3-month edoxaban treatment groups in the low (10.1% vs 7.6%), intermediate (8.8% vs 5.0%), and high (13.9% vs 12.6%) score subgroups., Conclusion: A 12-month compared with 3-month edoxaban treatment showed a lower risk of thrombotic events in patients with cancer-associated isolated distal deep vein thrombosis in the intermediate and high modified Ottawa score subgroups but not in the low score subgroup, suggesting a limited benefit of extended anticoagulation therapy beyond 3 months in patients with low modified Ottawa score., Competing Interests: Declaration of competing interests Y.Y. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo and grant support from Bayer Healthcare and Daiichi Sankyo. T.M. reports lecturer's fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; manuscript fees from Bristol-Myers Squibb and Pfizer; and advisory board for Novartis and Teijin. Y.N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo. Y.O. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo and research funds from Bayer Healthcare and Daiichi Sankyo. N.I. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi Sankyo. Y.T. received lecture fees from AstraZeneca, Chugai Pharmaceutical, Bristol-Myers Squibb, Kyowa Kirin, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceutical, and Daiichi Sankyo and grant support from Daiichi Sankyo, AstraZeneca, and Ono Pharmaceutical. S.I. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

T cell exhaustion refers to a progressive state in which T cells become functionally impaired due to sustained antigenic stimulation, which is characterized by increased expression of immune inhibitory receptors, but weakened effector functions, reduced self-renewal capacity, altered epigenetics, transcriptional programme and metabolism. T cell exhaustion is one of the major causes leading to immune escape of cancer, creating an environment that supports tumor development and metastatic spread. In addition, T cell exhaustion plays a pivotal role to the efficacy of current immunotherapies for cancer. This review aims to provide a comprehensive view of roles of T cell exhaustion in cancer development and progression. We summerized the regulatory mechanisms that involved in T cell exhaustion, including transcription factors, epigenetic and metabolic reprogramming events, and various microenvironmental factors such as cytokines, microorganisms, and tumor autocrine substances. The paper also discussed the challenges posed by T cell exhaustion to cancer immunotherapies, including immune checkpoint blockade (ICB) therapies and chimeric antigen receptor T cell (CAR-T) therapy, highlightsing the obstacles encountered in ICB therapies and CAR-T therapies due to T cell exhaustion. Finally, the article provides an overview of current therapeutic options aimed to reversing or alleviating T cell exhaustion in ICB and CAR-T therapies. These therapeutic approaches seek to overcome T cell exhaustion and enhance the effectiveness of immunotherapies in treating tumors., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Honokiol (HNK) is one of the bioactive ingredients from the well-known Chinese herbal medicine Magnolia officinalis, and its research interests is rising for its extensive pharmacological activities, including novel therapeutic effect on ulcerative colitis (UC). However, further application of HNK is largely limited by its unique physicochemical properties, such as poor water solubility, low bioavailability, as well as unsatisfied targeting efficacy for inflammatory lesions. In this study, we constructed galactosylation modified PLGA nanoparticles delivery system for efficient target delivery of HNK to the colitic lesions, which could lay a research foundation for the deep development of HNK for the treatment of UC. D-galactose was grafted by chemical coupling reactions with PLGA to prepare Gal-PLGA, which was used as a carrier for HNK (Gal-PLGA@HNK nanoparticles (NPs)). To improve the colon targeting efficiency by oral administration of the NPs, Eudragit S100 was used for wrapping on the surface of Gal-PLGA@HNK NPs (E/Gal-PLGA@HNK NPs). Our results showed that the encapsulation efficiency and drug loading capacity of E/Gal-PLGA@HNK NPs were 90.72 ± 0.54% and 8.41 ± 0.02%, respectively. Its average particle size was 242.24 ± 8.42 nm, with a PDI value of 0.135 ± 0.06 and zeta-potential of -16.83 ± 1.89 mV. The release rate of HNK from E/Gal-PLGA@HNK NPs was significantly decreased when compared with that of free HNK in simulated gastric and intestinal fluids, which displayed a slow-releasing property. It was also found that the cellular uptake of E/Gal-PLGA@HNK NPs was significantly increased when compared with that of free HNK in RAW264.7 cells, which was facilitated by D-galactose grafting on the PLGA carrier. Additionally, our results showed that E/Gal-PLGA@HNK NPs significantly improved colonic atrophy, body weight loss, as well as reducing disease activity index (DAI) score and pro-inflammatory cytokine levels in UC mice induced by DSS. Besides, the retention time of E/Gal-PLGA@HNK NPs in the colon was significantly increased when compared with that of other preparations, suggesting that these NPs could prolong the interaction between HNK and the injured colon. Taken together, the efficiency for target delivery of HNK to the inflammatory lesions was significantly improved by galactosylation modification on the PLGA carrier, which provided great benefits for the alleviation of colonic inflammation and injury in mice., 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 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) is a serious health problem worldwide, which ultimately leads to end-stage renal disease (ESRD). Renal fibrosis is the common pathway and major pathological manifestation for various CKD proceeding to ESRD. However, the underlying mechanisms and effective therapies are still ambiguous. Early growth response 2 (EGR2) is reportedly involved in organ formation and cell differentiation. To determine the role of EGR2 in renal fibrosis, we respectively confirmed the increased expression of EGR2 in kidney specimens from both CKD patients and mice with location in proximal tubules. Genetic deletion of EGR2 attenuated obstructive nephropathy while EGR2 overexpression further promoted renal fibrosis in mice subjected to unilateral ureteral obstruction (UUO) due to extracellular matrix (ECM) deposition mediating by partial epithelial-mesenchymal transition (EMT) as well as imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs (TIMPs). We found that EGR2 played a critical role in Smad3 phosphorylation, and inhibition of EGR2 reduced partial EMT leading to blockade of ECM accumulation in cultured human kidney 2 cells (HK2) treated with transforming growth factor β1 (TGF-β1). In addition, the transcription co-stimulator signal transducer and activator of transcription 3 (STAT3) phosphorylation was confirmed to regulate the transcription level of EGR2 in TGF-β1-induced HK2 cells. In conclusion, this study demonstrated that EGR2 played a pathogenic role in renal fibrosis by a p-STAT3-EGR2-p-Smad3 axis. Thus, targeting EGR2 could be a promising strategy for CKD treatment., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Thrombocytopenia is common among burn patients. Platelet transfusion is frequently administered to increase platelet counts. However, it is not clear whether platelets affect the outcome after transfusion among adult burn patients with thrombocytopenia. Our aim is to explore whether platelet transfusion affects the prognosis of adult burn patients with thrombocytopenia., Methods: We undertook a retrospective analysis of 368 adult burn victims with thrombocytopenia from the Department of Burn at the First Affiliated Hospital of Nanchang University, China, from January 2014 to July 2021. Propensity score matching (PSM) was utilized to reduce selection bias and confounding factors. After PSM, the platelet transfusion group and the no-platelet transfusion group each had 46 patients. Our primary outcome was 30-day all-cause mortality., Results: Logistic multivariate regression analysis showed that third-degree burn area [β = -0.040, odds ratio (OR) = 1.052, 95 % confidence interval (CI) = 1.015-1.091] and platelet transfusion (OR =2.227, 95 % CI = 0.473-10.483) were independent risk factors (P < 0.05). KaplanMeier analysis showed that the 30-day mortality of patients in the platelet transfusion group and no-platelet transfusion group were 47.8 % and 19.6 %, respectively (P < 0.05) CONCLUSION: Platelet transfusion was an independent risk factor for 30-day mortality in adult burn patients with thrombocytopenia., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The authors aim to investigate the effect of music on hemodynamic fluctuations during induction of general anesthesia and reducing preoperative anxiety for women who underwent elective non-cardiac surgery., Methods: It is a multicenter, double-blind, randomized, parallel-group clinical trial. Patients were randomized 1:1 to either a Music Intervention group (MI) or a Control group (Control). The MI participants listened to their preferred music for more than 30 minutes in the waiting area. The State-Trait Anxiety Inventory (STAI) was used to measure anxiety levels in the groups, and hemodynamic parameters (Heart Rate [HR], Mean Arterial Pressure [MAP]) were continuously recorded before induction (T0), at loss of consciousness (T1), immediately before intubation (T2), and after intubation (T3). Intubation-related adverse events were also recorded. The primary outcome was the incidence of MAP changes more than 20 % above baseline during T0-T2., Results: A total of 164 patients were included in the final analyses. The incidence of MAP instability during T0-T2 was lower in the MI, and the 95 % Confidence Interval for the rate difference demonstrated the superiority of MI. HR instability was less frequent in MI participants both in T0-T2 and T2-T3. The overall incidence of preoperative anxiety was 53.7 % (88/164). After the music intervention, the mean score of STAI was significantly lower in the MI than in the Control, with a between-group difference of 8.01., Conclusions: Preoperative music intervention effectively prevented hemodynamic instability during anesthesia induction and significantly reduced preoperative anxiety in women undergoing elective non-cardiac surgery., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)