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Acute lung injury (ALI) arises from an excessive inflammatory response, usually progressing to acute respiratory distress syndrome (ARDS) if not promptly addressed. There is currently a limited array of effective treatments available for ALI. In this study, we developed disulfide bond-bridged prodrug self-assembled nanoparticles (referred to as DSSS NPs). These nanoparticles were consisted of Dexamethasone (Dex) and stearic acid (SA), and were designed to target and treat ALI. DSSS NPs demonstrated a substantial drug loading capacity with 37.75 % of Dex, which is much higher than conventional nanomedicines (usually < 10 %). Moreover, they exhibited the potential to specifically target injured lung tissue and inflammatory microenvironment-responsive release drugs. Consequently, DSSS NPs reduced significantly the levels of pro-inflammatory cytokines and tissue damage in mice with ALI induced by lipopolysaccharide (LPS). Overall, DSSS NPs offer a promising strategy for treatment of acute lung injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Methane (CH 4 ) is the second most abundant greenhouse gas. China is the largest CH 4 emitter in the world, with coal mine methane (CMM) being one of the main anthropogenic contributions. Thus, there is an urgent need for comprehensive estimates and strategies for reducing CMM emissions in China. However, the development of effective strategies is currently challenged by a lack of information on temporal variations in the contributions of different CMM sources and the absence of provincial spatial analysis. Here, considering five sources and utilization, we build a comprehensive inventory of China's CMM emissions from 1980 to 2022 and quantify the contributions of individual sources to the overall CMM emissions at the national and provincial levels. Our results highlight a significant shift in the source contributions of CMM emissions, with the largest contributor, underground mining, decreasing from 89% in 1980 to 69% in 2022. Underground abandoned coal mines, which were ignored or underestimated in past inventories, have become the second source of CMM emissions since 1999. From 2011 to 2022, we identified Shanxi, Guizhou, and Shaanxi as the three largest CMM-emitting provinces, while the Emissions Database for Global Atmospheric Research (EDGAR) v8 overestimated emissions from Inner Mongolia, ranking it third. Notably, we observed a substantial decrease (exceeding 1 Mt) in CMM emissions in Sichuan, Henan, Liaoning, and Hunan between 2011 and 2022, which was not captured by EDGAR v8. To develop targeted CMM emission reduction strategies at the provincial level, we classified 31 provinces into four groups based on their CMM emission structures. In 2022, the number of provinces with CMM emissions mainly from abandoned coal mines has exceeded that of provinces with mainly underground mines, which requires attention. This study reveals the characteristics of the source of CMM emissions in China and provides emission reduction directions for four groups of provinces., 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.)

Glacial lake ecosystems are experiencing rapid changes due to accelerated glacier retreat. As glaciers recede, their influence on downstream habitats diminishes, potentially affecting the biodiversity of glacial lake microbial communities. However, there remains a knowledge gap regarding how bacterial biodiversity patterns in glacial lakes are altered by diminishing glacial influence. Here, we investigated shifts in bacterial communities in paired water and sediment samples collected from seven glacial lakes on the Tibetan Plateau, using a space-for-time substitution approach to understand the consequences of glacier retreat. Our findings reveal that bacterial diversity in lake water increases significantly with a higher glacier index (GI), whereas sediment bacterial diversity exhibits a negative correlation with GI. Both the water and sediment bacterial communities display significant structural shifts along the GI gradient. Notably, reduced glacial influence decreases the complexity of bacterial co-occurrence networks in lake water but enhances the network complexity in sediment. This divergence in diversity and co-occurrence patterns highlights that water and sediment bacterial communities respond differently to changes in glacial influence in these lake ecosystems. This study provides insights into how diminishing glacial influence impacts the bacterial biodiversity in glacial lake water and sediments, revealing contrasting patterns between the two habitats. These findings emphasize the need for comprehensive monitoring to understand the implications of glacier retreat on these fragile ecosystems., (© 2024. The Author(s).)

Two Co(II) metal-organic frameworks (Co-MOFs), namely, [Co(DMTDC)(bimb)] n ( Co-MOF-1 ) and {[Co(DPTDC)(bimb)(H 2 O)]·2DMF} n ( Co-MOF-2 ) (H 2 DMTDC = 3,4-dimethylthieno[2,3- b ]thiophene-2,5-dicarboxylic acid, H 2 DPTDC = 3,4-diphenylthieno[2,3- b ]thiophene-2,5-dicarboxylic acid, bimb = 1,4-bis((1 H -imidazol-1-yl)methyl)benzene), were obtained by the reaction of flexible N-containing ligand bimb and two structurally related thiophene-containing ligands H 2 DMTDC and H 2 DPTDC, respectively. These Co-MOFs displayed a 3D framework and porous structure, respectively. Co-MOF-1 and the activated sample Co-MOF-2' could act as green heterogeneous catalysts for the one-pot multicomponent Biginelli reaction, specifically the dehydration condensation process involving aldehydes, acetoacetates, and urea to yield dihydropyrimidin-2(1 H )-ones. The reaction has advantages such as solvent-free conditions, water as only byproduct, readily accessible starting materials, excellent functional group compatibility, and simple operation. Both catalysts exhibited a wide substrate scope and maintained significant catalytic activity over five cycles. The special catalytic performance may be ascribed to functional groups within the ligand.

Two Co-based supramolecular isomers were synthesized from a fluorinated carboxylic acid ligand under hydrothermal conditions at varying temperatures. Both exhibited similar one-dimensional chain structures while different bending connections of the aromatic rings led to different supramolecular structures, namely CoCP-1 and CoCP-2, respectively. The structural differences of two isomers resulted in discrepant performance with regards to luminescence sensing and catalysis. CoCP-1 demonstrated more significant luminescence quenching activity toward biomarkers 2,6-dipyridinoic acid (DPA) and high vanilloid acid (HVA), which could be distinguished in the presence of Eu3+. The limit of detection (LOD) was found to be as low as 3.4 and 1.3 μM, respectively. The recovery rate of for HVA and DPA was within the range of 89.6-101.2% and 99.7-117.9% in simulated urine and serum, respectively, indicating potential reliability in monitoring these two analytes in real samples. Notably, CoCP-2 exhibited catalytic activity for the oxidation of thioethers to sulfoxides. Our finding here suggests that the coordination conformation of the ligands within supramolecular isomers plays a pivotal role in determining the structure and luminescence sensing/catalysis performance., (© 2024 Wiley‐VCH GmbH.)

Two-photon photodynamic therapy (TP-PDT) offers an innovative approach to cancer treatment that utilizes near-infrared light to activate photosensitizers and generate reactive oxygen species (ROS) for targeted cancer cell elimination. TiO 2 -CUR-Sofast (TCS), which uses TiO 2 nanoparticles and Sofast cationic polymer to modify curcumin (CUR), has demonstrated potential as a photosensitizer under visible light irradiation, addressing the limitations of CUR's narrow spectral range and low bioavailability. This study explores the utility of the two-photon technique to activate TCS within the infrared spectrum, aiming to enhance ROS production and penetration depth compared to traditional CUR. TCS exhibits a significantly higher ROS production at 900 nm excitation wavelength, approximately 6-7 times that of CUR, signifying a substantial increase in efficiency. In TP-PDT, TCS showed significant phototoxicity against HeLa and T24 cell lines compared to CUR. Furthermore, TCS's photodynamic efficacy is further confirmed by cell apoptosis and necrosis studies, where approximately 89 % of cells treated with TCS under 900 nm light irradiation were observed in an apoptosis/necrosis state. And the TP-PDT effect in deep tissue was simulated using pig skin. It shows that the two-photon excitation has a significant penetration depth advantage over the single-photon excitation. These results indicate that the two-photon PDT scheme of TCS has greater potential than the single-photon PDT scheme in the treatment of cancer, and provides an experimental foundation for the effective treatment of deep lesions., 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.)

Vancomycin, a crucial antibiotic for Gram-positive bacterial infections, requires therapeutic drug monitoring (TDM). Contemporary guidelines advocate for AUC-based monitoring; however, using Bayesian programs for AUC estimation poses challenges. We aimed to develop and evaluate a simplified AUC estimation equation using a steady-state trough concentration (C trough ) value. Utilizing 1,034 TDM records from 580 general hospitalized patients at a university-affiliated hospital in Ulsan, we created an equation named SSTA that calculates the AUC by applying C trough , body weight, and single dose as input variables. External validation included 326 records from 163 patients at a university-affiliated hospital in Seoul (EWUSH) and literature data from 20 patients at a university-affiliated hospital in Bangkok (MUSI). It was compared with other AUC estimation models based on the C trough , including a linear regression model (LR), a sophisticated model based on the first-order equation (VancoPK), and a Bayesian model (BSCt). Evaluation metrics, such as median absolute percentage error (MdAPE) and the percentage of observations within ±20% error (P20), were calculated. External validation using the EWUSH data set showed that SSTA, LR, VancoPK, and BSCt had MdAPE values of 6.4, 10.1, 6.6, and 7.5% and P20 values of 87.1, 82.5, 87.7, and 83.4%, respectively. External validation using the MUSI data set showed that SSTA, LR, and VancoPK had MdAPEs of 5.2, 9.4, and 7.2%, and P20 of 95, 90, and 95%, respectively. Owing to its decent AUC prediction performance, simplicity, and convenience for automated calculation and reporting, SSTA could be used as an adjunctive tool for the AUC-based TDM., Competing Interests: The authors declare no conflict of interest.

Mosquitoes, as temperature-sensitive ectothermic vectors, exhibit temperature-dependence. This study investigates Culex pipiens pallens (Cx. pallens) responses to abrupt temperature increases and their implications on mosquito physiology. First instar larvae (24hr post hatching) and newly enclosed adults (24hr post emergence) were separately exposed to heat shock regimes of 33°C, 37°C, and 42°C for 3 days alongside a control temperature of 27°C. Results showed that mortality was triggered at 42°C within a day. Adult male mosquitoes were less tolerant to all temperatures than larvae and adult females (p < 0.05). Exposing larvae to constant temperatures for 3 days significantly decreased larvae's development time, growth rate and adult emergence (p < 0.05). Reproductive fitness was significantly reduced (p < 0.05) in males emerging from larvae exposed to 37°C. Life table parameters showed significant increased mortality rate, kill power and decreased life expectancy at the embryonic stage (p < 0.05). Furthermore, heatwaves deactivated the Transient receptor protein ankyrin 1 at 37°C (p < 0.05) in larvae but not adults. Calmodium, Heat shock protein 90, and small heat shock protein expression were significantly decreased in larvae at 37°C (p < 0.05) as compared to larvae raised at 33°C and 27°C. In conclusion, we classified the heat waves into three categories: adaptable (33°C), critical (37°C), and fatal (42°C). Prolonged exposure of Culex pallens larvae to extreme heat affects the male reproductive output. These findings may serve as an important reference for forecasting vector and pest dynamics and used to tailor mosquito prevention and control measures., Competing Interests: Declaration of competing interest None of the authors have a conflict of interest to disclose, (Copyright © 2024. Published by Elsevier B.V.)

Liver fibrosis is characterized by the excessive accumulation of extracellular matrix proteins, which can lead to cirrhosis and liver cancer. Metabolic dysfunction-associated steatosis liver diseases are common causes of liver fibrosis, sharing a similar pathogenesis with carbon tetrachloride (CCl₄) exposure. This process involves the activation of hepatic stellate cells (HSCs) into myofibroblasts. However, the detailed mechanism and effective treatment strategies require further investigation. In this study, we uncovered a negative correlation between VDR expression and YAP within HSCs. Subsequently, we demonstrated that VDR exerted a downregulatory influence on YAP transcriptional activity in HSCs. Intriguingly, activation VDR effectively inhibited the culture induced activation of primary HSCs by suppressing the transcriptional activity of early YAP. Furthermore, in vivo results manifested that hepatic-specific deletion of YAP/TAZ ameliorates CCl 4 -induced liver fibrosis, and nullified the antifibrotic efficacy of VDR. Importantly, a YAP inhibitor rescued the exacerbation of liver fibrosis induced by hepatic-specific VDR knockout. Moreover, the combined pharmacological of VDR agonist and YAP inhibitor demonstrated a synergistic effect in diminishing CCl 4 -induced liver fibrosis, primary HSCs activation and hepatic injury in vivo. These effects were underpinned by their collective ability to inhibit HSC activation through AMPK activation, consequently curbing ATP synthesis and HSCs proliferation. In conclusion, our results not only revealed the inhibition of VDR on YAP-activated liver stellate cells but also identified a synergistic effect of VDR agonist and YAP inhibitor in an AMPKα-dependent manner, providing a practical foundation for integration of multi-targeted drugs in the therapy of CCl 4 -induced hepatic fibrosis., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Viruses constitute the most diverse and abundant biological entities on Earth. However, our understanding of this tiniest life form in complex ecosystems remains limited. Here, we recover 20,102 viral OTUs from twelve intertidal zones along the Chinese coasts. Our analysis demonstrates high viral diversity and functional potential in intertidal zones, encoding important functional genes that can be potentially transferred to microbial hosts and mediate elemental biogeochemical cycles, especially carbon, phosphate and sulfur. Virus-host abundance dynamics vary among different microbial lineages. Viral community composition is closely associated with environmental conditions, including dissolved organic matter. Concordant biogeographic patterns are observed for viruses and microbes. Viral communities are generally habitat specific with low overlaps between intertidal and other habitats. Environmental factors and geographic distance dominate the compositional variation of intertidal viromes. Overall, these findings expand our understanding of intertidal viromes within an ecological framework, providing insights into the virus-host coevolutionary arms race., (© 2024. The Author(s).)

Objectives: This study aimed to investigate the satisfaction levels of graduate residents in Guizhou Province and analyse the factors influencing their satisfaction., Methods: A cross-sectional survey was conducted using a simple random sampling method with all graduate residents from 24 hospitals in Guizhou Province. The survey covered the residents' demographic information, information about the training hospitals and satisfaction survey responses. Statistical analyses were performed using SPSS 29.0, including descriptive statistics using component ratios, binomial distribution tests for specific satisfaction situations, X 2 tests for between-group comparisons and binary logistic regression analyses to analyse the associations between residency satisfaction and related factors. The significance level was set at α=0.05., Results: The survey included 1070 graduate residents of Guizhou Province, China, including 500 males (46.7%) and 570 females (53.3%). The satisfaction questionnaire revealed that 23.8% were very satisfied; 45.4% were somewhat satisfied; and 26.4%, 2.3% and 2.1% were average, somewhat dissatisfied and very dissatisfied, respectively. Factors influencing residency satisfaction included gender, age, training base level, identity type, training participation year and average monthly income., Conclusion: Based on this study, the satisfaction of graduate residents in Guizhou Province, China, is relatively lower than that in other countries and provinces. Therefore, Guizhou Province should take appropriate measures to address these influencing factors and enhance residency training satisfaction, thereby improving the residency training quality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Over the last four decades, research on DNA as a functional material has primarily  focused on its predictable conformation and programmable interaction. However, its low energy consumption, high responsiveness and sensitivity also make it ideal for designing specific signaling pathways, and enabling the development of molecular computers. This review mainly discusses recent advancements  in the utilization of DNA nanotechnology for molecular computer, encompassing applications in storage, cryptography and logic circuits. It elucidates the challenges encountered in the application process and presents solutions exemplified by representative works. Lastly, it delineates the challenges and opportunities within this filed., (© 2024 Wiley‐VCH GmbH.)

A unary system is the most conceptually concise design for conducting self-assembly. However, in most DNA-guided self-assembly schemes, a unary system has rarely been adopted because of the inherent challenge of strictly decoupling the monomer synthesis process from the assembly process, which may directly lead to the inaccurate control over assembly. Herein, we provide a multi-stimulus-triggered assembly strategy based on the DNA origami structure, which allows the unary system to realize controllable crystallization and phase transition by exerting allosteric stimuli. We intentionally introduced a specific DNA stimulus to convert the self-aggregation of functionalized groups into the connection of nearby monomers, thus producing multidimensional high-quality crystals. Furthermore, this unary system can undergo a phase transition from simple cubic to face-centered cubic with the introduction of more cation stimuli. We believe that this dynamic stimulation strategy can offer a novel solution for fabricating materials with on-demand modulation.

Chewing areca nuts is popular in China. Areca alkaloids are the major toxic compounds in areca nuts. In this study, the levels of four areca alkaloids (i.e. arecoline, arecaidine, guvacoline and guvacine) in 119 areca nut samples were analyzed and 3030 areca nut consumption questionnaires were collected to investigate the exposure to areca alkaloids in the Chinese populations through areca nut chewing. The levels of arecoline, arecaidine, guvacoline and guvacine in different areca nut products were 0.46-4.97 mg/g, 0.57-7.51 mg/g, 0.08-1.44 mg/g and 0.03-8.48 mg/g, respectively. Chewing fresh areca fruits was the main source of arecoline and the total areca alkaloids exposure. The estimated daily intake (EDI) of arecoline and the total areca alkaloids for the Chinese populations were 1.126 and 2.625 mg/kg BW/day for average exposure, 4.411 and 9.739 mg/kg BW/day for high exposure (P95th). The EDI varied with age and gender. The young male population (≤ 34 years) had the highest EDI than other populations. Concentrated and focused efforts are required to educate the general public, especially the young male population, about the risks of areca nut chewing to reduce exposure to areca alkaloids of the Chinese population., Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05966-6., Competing Interests: Conflict of interestThe 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., (© Association of Food Scientists & Technologists (India) 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Aims: To compare the time in range (TIR) obtained from self-monitoring of blood glucose (SMBG) with that obtained from continuous glucose monitoring (CGM), and explore the relationship of TIR with microalbuminuria outcome, HOMA-IR and HOMA-β test., Methods: We recruited 400 patients with type 2 diabetes to carry out blood glucose monitoring by both SMBG and CGM for 3 consecutive days. TIR, TAR, TBR and other blood glucose variation indices were calculated respectively through the glucose data achieved from SMBG and CGM. The HOMA-IR and HOMA-β test was evaluated by an oral glucose tolerance test. Urinary microalbumin-to-creatinine ratio completed in the laboratory., Results: The median (25 %, 75 % quartile) of TIR CGM and TIR SMBG were 74.94(44.90, 88.04) and 70.83(46.88, 87.50) respectively, and there was no significant difference, p = 0.489; For every 1 % increase in TIR CGM , the risk of microalbuminuria decreased by 1.6 % (95%CI:0.973, 0.995, p = 0.006) and for every 1 % increase in TIR SMBG , the risk of microalbuminuria decreased by 1.3 % (95%CI:0.975, 0.999, p = 0.033). Stepwise multiple linear regression analysis showed an independent positive correlation between TIR (including TIR CGM and TIR SBMG ) and LnDI30 and LnDI120 levels (p = 0.000)., Conclusions: The TIR calculated by SMBG was highly consistent with that reported by CGM and was significantly associated with the risk of microalbuminuria and the HOMA-β. Higher TIR quartiles were associated with lower incidence of microalbuminuria as well as higher lever of HOMA-β. For patients with limited CGM application, SMBG-derived TIR may be an alternative to CGM-derived TIR, to assess blood glucose control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Bombesin receptor-activated protein (BRAP), encoded by the C6orf89 gene in humans, is expressed in various cells with undefined functions. BC004004, the mouse homologue of C6orf89, has been shown to play a role in bleomycin-induced pulmonary fibrosis through the use of a BC004004 gene knockout mouse (BC004004 -/- ). In this study, we investigated the potential involvement of BRAP in renal fibrosis using two mouse models: unilateral ureteral obstruction (UUO) and type 2 diabetes mellitus induced by combination of a high-fat diet (HFD) and streptozocin (STZ). BRAP or its homologue was expressed in tubular epithelial cells (TECs) in the kidneys of patients with chronic kidney disease (CKD) and in BC004004 +/+ mice. Compared to control mice, BC004004 -/- mice exhibited attenuated renal injury and renal fibrosis after UUO or after HFD/STZ treatment. Immunohistochemistry and immunoblot analyses of the kidneys of BC004004 +/+ mice after UUO surgery showed a more significant decrease in E-cadherin expression and a more significant increase in both α smooth muscle actin (α-SMA) and vimentin expression compared to BC004004 -/- mice. Additionally, stimulation with transforming growth factor-β1 (TGF-β1) led to a more significant decrease in E-cadherin expression and a more significant increase in α-SMA and vimentin expression in isolated TECs from BC004004 +/+ than in those from BC004004 -/- mice. These results suggest that an enhanced epithelial-mesenchymal transition (EMT) process occurred in TECs in BC004004 +/+ mice during renal injury, which might contribute to renal fibrosis. The loss of the BRAP homologue in BC004004 -/- mice suppressed EMT activation in kidneys and contributed to the suppression of fibrosis during renal injury., (© 2024 John Wiley & Sons Australia, Ltd.)

Biomass-based adhesives are gaining attention as environmentally friendly alternatives to toxic petroleum-based adhesives. However, biomass-based adhesives exhibit poor adhesive properties and are highly susceptible to failure in humid environments. In this study, a zein-based adhesive with high adhesive strength and good water resistance was prepared by optimizing the solvent composition and adding tannic acid. Adding 10 wt% acetic acid to an aqueous ethanol solvent increased the shear strength by 45.4 % to 3.09 MPa. Moreover, the addition of 6 wt% tannic acid improved the shear strength of the zein-based adhesive in humid environments from 0.63 to 1.58 MPa. The tannic acid-reinforced zein-based adhesive exhibited good adhesive strength in both humid and dry environments, which was maintained for 30 days on glass, and could be applied to a wide range of substrates. Moreover, the adhesive showed an antioxidant activity >94 %, excellent thermal stability, biocompatibility, and antibacterial effect. Therefore, this adhesive has great application prospects in medical, packaging, and other fields., 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.)

Objective: We sought to develop a risk prediction model for predischarge major mitral valve (MV) residual lesions or unplanned MV reinterventions following congenital MV repair., Methods: Patients who underwent congenital MV repair (excluding primary repair, but including secondary repair, of canal-type defects) at a single institution from January 2000 to December 2020 and survived to discharge were retrospectively reviewed. The primary outcome was major MV residua (mean gradient >6 mm Hg or moderate or greater regurgitation on the discharge echocardiogram) or predischarge unplanned MV reintervention. Risk factors of interest included age, single-ventricle physiology, preoperative and intraoperative postrepair MV stenosis and regurgitation severity, MV annular diameter z score, systemic ventricle ejection fraction, unfavorable anatomy, concomitant left-heart procedure, and various technique-related categories. Logistic regression was used to develop a weighted risk score for the primary outcome. Internal validation using bootstrap-resampling was performed., Results: Of 866 patients who underwent congenital MV repair at a median age of 2.7 years (interquartile range, 0.7-9.1 years), 202 (23.3%) patients developed the primary outcome. The final risk prediction model had a C-statistic of 0.82 (95% confidence interval, 0.78-0.85). A weighted risk score was formulated per the variables in this model. The median risk score was 8 (interquartile range, 6-11) points. Patients were categorized as low (score 0-5), medium (score 6-10), high (score 11-15), or very high (score ≥16) risk. The probability of the primary outcome was 5.0 ± 1.7%, 15.2 ± 6.7%, 45.9 ± 12.6%, and 76.7 ± 8.8% for low-, medium-, high-, and very-high-risk patients, respectively., Conclusions: Our risk prediction model may guide prognostication of patients following congenital MV repair., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to identify the independent factors associated with intertemporal decision-making and to examine its relationship with diabetes self-management behaviors, glucose variability, and diabetes complications in patients with diabetes., Methods: A cross-sectional study using convenience sampling (n = 368) was conducted in patients with type 2 diabetes (T2DM) between November 2021 and April 2023. Data were collected using self-reported questionnaires and retrieval of clinical information from medical records. Intertemporal decision-making was operationalized using delay discounting. The outcome variables included diabetes self-management behaviors, A1C, diabetic retinopathy, and carotid artery disease. Hierarchical regression and binary logistic regression models were used to explore the relationships among intertemporal decision-making, self-management, A1C, and carotid artery disease., Results: The analyses showed that intertemporal decision-making was negatively associated with physical activity and carotid artery disease, in which individuals with lower delay discounting tended to have healthier physical activity; when the delay discounting rate increased 1 unit, the risk of the carotid artery disease increased by 39.8%., Conclusions: The study reveals that a lower delay discounting can promote healthier physical activity and decrease the incidence of carotid artery disease. These results offer new knowledge for researchers and clinicians to consider intertemporal decision-making in developing interventional programs to improve physical activity and reduce carotid artery complication in patients with T2DM when providing care., Competing Interests: Declaration of Conflicting InterestsAll authors have no conflicts of interest to report.

Chitosan is a potentially suitable material for wound dressing, but is undesirably water-insoluble. Although chitosan can be modified to produce water-soluble derivatives, the best chitosan derivative for wound dressings remains unclear. The present study introduced three water-soluble chitosan derivatives, namely, carboxymethyl chitosan, quaternized chitosan (QCS), and carboxymethyl quaternized chitosan, and explored the physical properties, biochemical properties, and wound care effectiveness of films of these derivatives. The QCS-based film exhibited higher absorption ability, mechanical properties, water-vapor permeability, electroconductivity, and antioxidant capacity than the other films. Most importantly, the cationic quaternary ammonium groups facilitated the antibacterial activity (>95 %) and blood coagulant capacity of the QCS-based film. As this film also promoted wound healing, it presented as an ideal candidate for wound dressings., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cellobiose 2-epimerase (CE) catalyzes the conversion of the lactose into its high-value derivatives, epilactose and lactulose, which has great prospects in food applications. In this study, CE sequences from the Qinghai-Tibet Plateau gene catalogue, we screened these for structural flexibility through molecular dynamics simulation to identify potential psychrophilic CE candidates. One such psychrophilic CE we termed psyCE demonstrated exceptional epimerization activity, achieving an optimum activity of 122.2 ± 1.6 U/mg. Its kinetic parameters (K cat and K m ) for epimerization activity were 219.9 ± 5.6 s -1 and 261.9 ± 18.1 mM, respectively, representing the highest K cat recorded among known cold-active CEs. Notably, this is the first report of a psychrophilic CE. The psyCE can effectively produce epilactose at 8 °C, converting 20.3 % of 200 mM lactose into epilactose within four hours. These findings suggest that psyCE is highly suitable for cryogenic food processing, and glaciers may serve as a valuable repository of psychrophilic enzymes., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The purpose of this study was to explore Adverse Childhood Experiences (ACEs) as a moderator between sleep duration/irregularity and overweight/obesity in U.S. adolescents. Using the National Survey of Children's Health 2017-2018 cross-sectional dataset, we included adolescents with available sleep and Body Mass Index (BMI) data. In a sample of 24,100 adolescents (mean age = 13.56 years, 49.35% female; 51% White), parents reported adolescent's sleep duration/irregularity, and number of ACEs. Logistic regression estimated the interaction between sleep duration/irregularity and the number of ACEs on overweight/obesity risk (BMI ≥ 85th percentile-for-age) using a stepwise approach and accounting for complex survey design. In the 24,100 adolescents, 33% were overweight/obese, 50% had ≥ 1 ACE, 37% slept < 8-10 h/night, and 14% had irregular sleep. Accounting for covariates and ACEs, every hour increase in sleep duration was associated with 6% decrease in overweight/obesity odds. There was a significant interaction between sleep duration and ACEs; the association between increasing sleep duration and decreasing odds of overweight/obesity was significant only in adolescents without ACEs (OR = 0.87, 95% CI [0.80, 0.95], p < 0.001). Increasing sleep duration is a recognized intervention target to decrease obesity risk, yet in adolescents experiencing ≥ 1 ACE, this protective role may be dampened. Future work may explore mechanisms for overweight/obesity development to inform interventions for adolescents facing adversity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Addressing levodopa-unresponsive freezing of gait (FOG) in Parkinson's disease (PD) presents a significant challenge. A randomized double-blinded trial evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in conjunction with transcutaneous magnetic spinal cord stimulation among 57 PD individuals experiencing levodopa-unresponsive FOG. Patients were randomized to receive dual-site stimulation involving bilateral primary motor cortex of the lower leg (M1-LL) and the lumbar spinal cord, single-site stimulation targeting bilateral M1-LL alone, or sham stimulation for 10 sessions. Low-frequency rTMS induced remarkable improvements in FOG, gait, and motor functions compared to sham at 1 day and 1 month postintervention. Notably, the dual-site protocol demonstrated superior efficacy in mitigating FOG and improving gait compared to the single-site approach, which correlated with a pronounced increase in short-interval intracortical inhibition of the abductor pollicis brevis. These findings underscore the potential of the cerebrospinal dual-site regimen as a promising approach for levodopa-unresponsive FOG and gait in PD., (© 2024. The Author(s).)

Purpose of Review: As science and technology continue to evolve, the potential harm of radiation to the human body cannot be overlooked. Radiation has the capacity to inflict cellular and body-wide damage. Polyphenols are a group of naturally occurring compounds that are found in an array of plant foods. Scientific studies have demonstrated that these compounds possess noteworthy anti-radiation efficacy. Furthermore, they have been observed to be less toxic at higher doses. In the present review, we discussed the mechanisms of ionizing radiation damage and the progress in the research on the radiation resistance mechanism of polyphenol compounds, to provide guidance for the prevention and treatment of radiation related diseases., Recent Findings: Food polyphenols can reduce the oxidative damage caused by ionizing radiation, clear free radicals, reduce DNA damage, regulate NF-KB, MAPK, JAK/STAT, Wnt and other signaling pathways, improve immune function, and have significant protective effects on radiation-induced inflammation, fibrosis, cancer and other aspects. In addition, it also has significant dual effects on radiation sensitization and radiation protection. Food polyphenols come from a wide range of sources, are abundant in daily food, and have no toxic side effects, demonstrating that food polyphenols have great advantages in preventing and treating radiation-related diseases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The objective of the study was to assess the potential association between the indel polymorphism (rs34802628) located within the intron of the collagen type ⅳ alpha 2 gene ( COL4A2 ) and the susceptibility to stomach adenocarcinoma (STAD) within a Chinese population., Methods: Peripheral venous blood samples were collected from a total of 497 STAD patients and 804 healthy control individuals to extract genomic DNA. The genotyping of the COL4A2 rs34802628 polymorphism was carried out using a polymerase chain reaction assay. Additionally, statistical analyses were conducted on the expression levels of COL4A2 mRNA using the GEPIA database. Meanwhile, the expression of COL4A2 mRNA was also validated by Real-time PCR using STAD tissue samples. Then, based on an analysis of patient tumor RNA seq data available from the Cancer Genome Atlas (TCGA), we assessed the prognostic value of mRNA expression of the COL4A2 gene in STAD patients using K-M plotter., Results: The study presented compelling evidence supporting an association between the rs34802628 polymorphism in the COL4A2 gene and susceptibility to STAD. Logistic regression analysis revealed that both the heterozygote and homozygote 4-bp del/del genotypes were significantly associated with a decreased risk of STAD, even after controlling for other variables (adjusted odds ratio [OR] = 0.663, 95% confidence interval [CI] 0.519-0.848, p  = 0.037; OR = 0.422, 95% CI 0.290-0.614, p  = 0.000005, respectively). Importantly, individuals carrying the 4-bp deletion allele demonstrated a notably lower risk of developing the disease (OR = 0.696, 95% CI 0.591-0.820, p  = 0.000014). Furthermore, Genotype-phenotype correlation studies in human STAD tissue samples demonstrated that the higher mRNA expression levels of COL4A2 were associated with the ins allele of rs34802628. Bioinformatics analysis revealed that higher expression of the COL4A2 gene was significant with development and poor prognosis of STAD., Conclusion: The results of our study provide strong evidence indicating a potential involvement of genetic variants in the COL4A2 gene in the development of STAD. Nonetheless, to validate and consolidate these findings, additional investigations incorporating larger sample sizes and functional experiments are necessary.

Background: Extended depth of focus (EDOF) and multifocal (Multi) intraocular lenses (IOL) can provide a fixed distance of near vision, which may result in some discomfort for patients who prefer different near distances. The aim of this study was to compare the vision, comfortable near distance (CND) and visual comfort in patients who underwent implantation of EDOF, Multi, and monofocal (Mono) IOLs., Methods: A total of 100 eyes were implanted with Tecnis ZXR00, ZMB00 or ZCB00 IOLs. Uncorrected distance, intermediate, and near visual acuity (UDVA, UIVA, and UNVA, respectively), corrected distance visual acuity (CDVA), the fluctuations of CND, the ability to see at comfortable or standard near distance and visual comfort were evaluated at 3-month postoperative., Results: At 3 months postoperative, the EDOF and Multi groups showed non-inferiority compared to the Mono group in the UDVA (P > 0.05) and CDVA (P > 0.05) but superiority in the UNVA (P < 0.001). The UIVA was better in the EDOF group, with comparable results for the Multi and Mono groups. There was no difference in preoperative and postoperative CND in the three groups. The CND visual acuity (CNDVA) was lower than the UNVA in the three groups, especially in the EDOF and Multi groups (P < 0.05). The CND effectively improved patients' near visual comfort and visual clarity, except for one patient in the Multi group who complained of severe fatigue and was unable to tolerate the experience at month 3., Conclusion: The EDOF and Multi IOLs achieved excellent visual quality and superior UNVA compared to the Mono IOL, but the CNDVA was significantly inferior to the UNVA. Patients' near visual experience can be effectively improved at their CND., (© 2024. The Author(s).)

Objectives: To develop and assess the efficacy of a novel combined patient-specific device (CPSD) for the accurate and safe insertion of infrazygomatic crest miniscrews in orthodontic procedures., Materials and Methods: Twenty-eight miniscrews were placed in the infrazygomatic crest region of 28 cadaver maxillae using the direct manual method (n = 14) or the CPSD (n = 14) based on preset trajectories. The CPSD, designed based on the integration model, included a positioning guide, an insertion guide, and a depth-limiting groove. Deviations in the insertion site, tip location, insertion angle, and biting depth between the preset and real insertion trajectories were calculated to evaluate the accuracy of miniscrew insertion. Classification frequencies of root proximity, sinus penetration depth, and biting depth of the miniscrew after insertion were also calculated to evaluate the safety of miniscrew insertion., Results: Regarding evaluation of accuracy, significant differences were observed in the deviation values of the insertion site, tip location, insertion angle, and biting depth between the CPSD and freehand groups (P = .001, P < .001, P < .001, P = .039, respectively). Regarding evaluation of safety, a significant difference was observed in the classification frequencies of root proximity between the two groups (P = .016)., Conclusions: Compared with manual insertion, CPSD could be a preferred method for safe and accurate insertion of infrazygomatic crest miniscrews for orthodontists., (© 0000 by The EH Angle Education and Research Foundation, Inc.)

Hepatobiliary and pancreatic diseases are becoming increasingly common worldwide and associated cancers are prone to recurrence and metastasis. For a more accurate treatment, new therapeutic strategies are urgently needed. The claudins (CLDN) family comprises a class of membrane proteins that are the main components of tight junctions, and are essential for forming intercellular barriers and maintaining cellular polarity. In mammals, the claudin family contains at least 27 transmembrane proteins and plays a major role in mediating cell adhesion and paracellular permeability. Multiple claudin proteins are altered in various cancers, including gastric cancer (GC), esophageal cancer (EC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), colorectal cancer (CRC) and breast cancer (BC). An increasing number of studies have shown that claudins are closely associated with the occurrence and development of hepatobiliary and pancreatic diseases. Interestingly, claudin proteins exhibit different effects on cancer progression in different tumor tissues, including tumor suppression and promotion. In addition, various claudin proteins are currently being studied as potential diagnostic and therapeutic targets, including claudin-3, claudin-4, claudin-18.2, etc. In this article, the functional phenotype, molecular mechanism, and targeted application of the claudin family in hepatobiliary and pancreatic diseases are reviewed, with an emphasis on claudin-1, claudin-4, claudin-7 and claudin-18.2, and the current situation and future prospects are proposed., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Du et al.)

Urogenital reconstructive malformation surgery is sometimes hampered by lack of tissue for the repair. We have previously shown that autologous micrografting allows for single-staged scaffold cellularization after surgical implantation. Here, a collagen-based scaffold reinforced with biodegradable mesh and a stent was implanted as a bladder conduit in ten full-grown female minipigs. We aimed to assess short-term regenerative outcomes, safety, and feasibility of implanting tubular urinary micrografted scaffolds versus acellular controls. Five scaffolds were embedded with autologous urothelial micrografts harvested perioperatively. After six weeks, all animals were assessed by cystoscopy, CT-urography, and microanatomical assessment of the urinary conduits. The procedure proved technically feasible within the confines of a regular surgical theater, with duration-times comparable to corresponding conventional procedures. No animals experienced postoperative complications, and all implanted conduits were patent at follow-up. Improved tissue regeneration was observed in the micrografted conduits compared with the acellular controls, including increased luminal epithelialization, increased cell proliferation, decreased cell apoptosis, and increased conduit vascularization. We concluded that single-staged on-site construction and implantation of tissue engineered urinary conduits proved feasible and safe, with improved regenerative potentials in micrografted conduits. This study presents a new approach to urinary conduits, and merits further investigations for advancement towards clinical translation., (© 2024. The Author(s).)

Parasitic helminths, taxonomically comprising trematodes, cestodes, and nematodes, are multicellular invertebrates widely disseminated in nature and have afflicted people continuously for a long time. Helminths play potent roles in the host through generating a variety of novel molecules, including some excretory/secretory products and others that are involved in intracellular material exchange and information transfer as well as the initiation or stimulation of immune and metabolic activation. The helminth-derived molecules have developed powerful and diverse immunosuppressive effects to achieve immune evasion for parasite survival and establish chronic infections. However, they also improve autoimmune and allergic inflammatory responses and promote metabolic homeostasis by promoting metabolic reprogramming of various immune functions, and then inducing alternatively activated macrophages, T helper 2 cells, and regulatory T cells-mediated immune responses. Therefore, a deeper exploration of the immunopathogenic mechanism and immune regulatory mechanisms of helminth-derived molecules exerted in the host is crucial for understanding host-helminth interactions as well as the development of therapeutic drugs for infectious or non-infectious diseases. In this review, we focus on the properties of helminth-derived molecules to give an overview of the most recent scientific knowledge about their pathogenic and pharmacopeial roles in immune-metabolic homeostasis.

Maternal immune activation (MIA) is critical for imparting neuropathology and altered behaviors in offspring; however, maternal-fetal immune cell populations have not been thoroughly investigated in MIA-induced autism spectrum disorders (ASDs). Here, we report the single-cell transcriptional landscape of placental cells in both PBS- and poly(I:C)-induced MIA dams. We observed a decrease in regulatory T (Treg) cells but an increase in the M1 macrophage population at the maternal-fetal interface in MIA dams. Based on the Treg-targeting approach, we investigate an immunoregulatory protein, the helminth-derived heat shock protein 90α (Sjp90α), that induces maternal Treg cells and subsequently rescues the autism-like behaviors in adult offspring. Furthermore, in vivo depletion of maternal macrophages attenuates placental inflammatory reaction and reverses behavioral abnormalities in adult offspring. Notably, Sjp90α induces CD4 + T cell differentiation via scavenger receptor A (SR-A) on the macrophage in vitro. Our findings suggest a maternal Treg-targeted approach to alleviate MIA-induced autism-like behavior in adult offspring., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

With the increase of chemotherapy frequency for breast cancer, the drug resistance rate of patients is rising, accompanied by cell invasion and metastasis, thus causing mortality. We aimed to explore the mechanism by which Platycodon grandiflorus affects breast cancer cells in terms of the doxorubicin (Dox) resistance and epithelial-mesenchymal transition (EMT) via the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. MCF-7/R cell lines with resistance to Dox were established. After 24 h of culture with DMEM (blank group), they were divided into Platycodon grandiflorus, Platycodon grandiflorus + Ophiopogon japonicus, Platycodon grandiflorus + Curcumae Rhizoma, Platycodon grandiflorus + Curcumae Rhizoma + U46619 groups. Flow cytometry, colony formation assay, as well as Transwell assay were performed to examine the cells for apoptosis, proliferation, and invasion, respectively. Western blotting was performed to measure the phosphorylated (p)-p38 MAPK-to-p38 MAPK ratio together with N-cadherin, vimentin, β-catenin, and E-cadherin protein expressions. Compared with the blank group, the half maximal inhibitory concentration (IC 50 ), number of cell colonies, number of invading cells and expressions of proteins related to EMT (i.e. N-cadherin, vimentin, and β-catenin) significantly reduced, but increases in apoptosis rate, p-p38 MAPK/p38 MAPK ratio and E-cadherin protein expression were observed in different groups (P < 0.05). Compared with the Platycodon grandiflorus + Curcumae Rhizoma group, the Platycodon grandiflorus + Curcumae Rhizoma + U46619 group had significantly decreased IC 50 , cell colony count, invading cell count and β-catenin, N-cadherin, and vimentin expressions, in addition to elevated E-cadherin protein expression, apoptosis rate, and p-p38 MAPK/p38 MAPK ratio (P < 0.05). Platycodon grandiflorus can reverse the resistance of breast cancer cells to Dox and regulate their biological activities by activating the p38 MAPK signaling pathway., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

This study addresses the challenge of controlling branching density and branch-type distribution in late-transition-metal-catalyzed chain walking polymerizations. We explored α-diimine Pd(II) complexes with incrementally increased ortho -aryl sterics for long-chain α-olefin (co)polymerization. Pd0 - Pd3 catalysts, which feature gradually increased ortho -aryl sterics and at least one small CH 3 substituent, exhibited similar 2,1-insertion fractions (44-50%), polymer branching densities (55-63/1000C), and melting temperatures (26-28 °C). In contrast, Pd4 with bulky ortho -aryl sterics covering all sides demonstrated a significant increase in 2,1-insertion fractions up to 82%, leading to "PE-like" polymers with high melting temperatures ( T m > 111 °C). This abrupt change in polymerization behavior, termed the "steric-deficient effect", contrasts with the gradual changes observed in similar Ni(II) systems that we reported previously. Furthermore, due to the rapid chain walking ability of Pd(II) catalysts in long-chain α-olefin (co)polymerization, these catalysts favor the production of polyolefins with higher proportions of methyl branches compared to those produced by Ni(II) catalysts. Particularly, these Pd(II) catalysts are capable of synthesizing functionalized semicrystalline copolymers by copolymerizing 1-octene with a variety of polar comonomers, thereby significantly altering the surface properties of the materials.

Water plays a vital role in the life cycle of plants, participating in various critical biochemical reactions during both non-photosynthetic and photosynthetic processes. Direct visualization of the metabolic activities of water in plants with high spatiotemporal resolution is essential to reveal the functional utilization of water. Here, stimulated Raman scattering (SRS) microscopy is applied to monitor the metabolic processes of deuterated water (D 2 O) in model plant Arabidopsis thaliana (A. thaliana). The work shows that in plants uptaking D 2 O/water solution, proton-transfer from water to organic metabolites results in the formation of C-D bonds in newly synthesized biomolecules (lipid, protein, and polysaccharides, etc.) that allow high-resolution detection with SRS. Reversible metabolic pathways of oil-starch conversion between seed germination and seed development processes are verified. Spatial heterogeneity of metabolic activities along the vertical axis of plants (root, stem, and tip meristem), as well as the radial distributions of secondary growth on the horizontal cross-sections are quantified. Furthermore, metabolic flow of protons from plants to animals is visualized in aphids feeding on A. thaliana. Collectively, SRS microscopy has potential to trace a broad range of matter flows in plants, such as carbon storage and nutrition metabolism., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Different nutrient load in the lake ecosystems trigger the regime difference and change of predominant biotype. The regulation of carbon (C) sequestration mode in the lacustrine sediments in response to this process need prudent clarification. Fluorescence measurements and high-throughput sequencing for functional genes cbbL and cbbM encoding C-fixing bacteria genus were executed for sediments from two representative regimes dominated by macrophyte and Cyanophyta, respectively. The results showed that humic-like and fulvic-acid like materials dominated the dissolved organic matter (DOM) from the algae and macrophyte-dominated lake regions, respectively. Microbial assimilation played critical influence on C fixation into the sediments in both of the two regimes. However, higher diversity was detected in macrophyte-dominated regime compared to that in Cyanophyta-dominated regime, suggesting that moderate nutrient levels facilitated the species richness of bacteria encoding functional genes concerning C fixation. Bacterial species and diversities varied between two regimes including predominant and rare taxa, suggesting that community structure alteration due to regime difference triggered the regulation the C sequestration mode and stability. Predominant genera manipulated the abundance of C-fixing bacteria genes in response to the regulation of nutrient levels. Noted that rare genera also responded to the regime difference and played key role in C sequestration into lacustrine sediments. Our results suggest that more abundant macrophyte-dominated regime facilitated the C sequestration in the lake ecosystems for atmospheric C reduction., 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.)

Apple polyphenols (APs) have gained attention for their various bioactivities, while no studies on anti-liver fibrosis activity are reported. This study evaluated the protective effect of APs on liver fibrosis using LPS-treated activated HSC-T6 cells and alcohol-treated liver fibrosis (ALF) mice. The results indicated that APs inhibited HSC-T6 cells activation in vitro and reduced the level of serum hyaluronic acid (HA) (p < 0.05), decreased fibrogenesis marker expression (p < 0.05), thereby alleviating ALF. In addition, APs (800 mg/kg b.w.) decreased the Firmicutes/Bacteroidetes ratio (p < 0.05) in ALF mice, inhibited LPS accumulation in the liver tissue and serum (p < 0.05), and significantly inhibited the TLR4/NF-κB/TGF-β signaling in mice liver. In conclusion, APs markedly ameliorated ALF, possibly by improving gut microbiota homeostasis, decreasing the translocation of bacterial endotoxins to the blood, and suppressing the TLR4/NF-κB/TGF-β signaling pathway, indicating its potential as lead compounds for functional foods and/or drugs against ALF., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetic retinopathy (DR) is a retinal disease caused by diabetes. If there is no intervention, it may even lead to blindness. Therefore, the detection of diabetic retinopathy is of great significance for preventing blindness in patients. Most of the existing DR detection methods use supervised methods, which usually require a large number of accurate pixel-level annotations. To solve this problem, we propose a self-supervised Equivariant Refinement Classification Network (ERCN) for DR classification. First, we use an unsupervised contrast pre-training network to learn a more generalized representation. Secondly, the class activation map (CAM) is refined by self-supervision learning. It first uses a spatial masking method to suppress low-confidence predictions, and then uses the feature similarity between pixels to encourage fine-grained activation to achieve more accurate positioning of the lesion. We propose a hybrid equivariant regularization loss to alleviate the degradation caused by the local minimum in the CAM refinement process. To further improve the classification accuracy, we propose an attention-based multi-instance learning (MIL), which weights each element of the feature map as an instance, which is more effective than the traditional patch-based instance extraction method. We evaluate our method on the EyePACS and DAVIS datasets and achieved 87.4% test accuracy in the EyePACS dataset and 88.7% test accuracy in the DAVIS dataset. It shows that the proposed method achieves better performance in DR detection compared with other state-of-the-art methods in self-supervised DR detection., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Aim: To analyze the spectrum of isolated pathogens and antibiotic resistance for ocular infections within 5y at two tertiary hospitals in east China., Methods: Ocular specimen data were collected from January 2019 to October 2023. The pathogen spectrum and positive culture rate for different infection location, such as keratitis, endophthalmitis, and periocular infections, along with antibiotic resistance were analyzed., Results: We included 2727 specimens, including 827 (30.33%) positive cultures. A total of 871 strains were isolated, 530 (60.85%) bacterial and 341 (39.15%) fungal strains were isolated. Gram-positive cocci (GPC) were the most common ocular pathogens. The most common bacterial isolates were Staphylococcus epidermidis (25.03%), Staphylococcus aureus (7.46%), Streptococcus pneumoniae (4.59%), Corynebacterium macginleyi (3.44%), and Pseudomonas aeruginosa (3.33%). The most common fungal genera were Fusarium spp. (12.74%), Aspergillus spp. (6.54%), and Scedosporium spp. (5.74%). Staphylococcus epidermidis strains showed more than 50% resistance to fluoroquinolones. Streptococcus pneumoniae and Corynebacterium macginleyi showed more than 90% resistance to erythromycin. The percentage of bacteria showing multidrug resistance (MDR) significantly decreased ( χ 2 =17.44, P =0.002)., Conclusion: GPC are the most common ocular pathogens. Corynebacterium macginleyi , as the fourth common bacterium, may currently be the local microbiological feature of east China. Fusarium spp. is the most common fungus. More than 50% of the GPC are resistant to fluoroquinolones, penicillins, and macrolides. However, the proportion of MDR strains has been reduced over time., Competing Interests: Conflicts of Interest: Li PP, None; Li L, None; Zhang JF, None; Qin B, None; Kang LH, None; Ji M, None; Guan HJ, None., (International Journal of Ophthalmology Press.)

In this study, the interaction mechanism and native conformational variation of trypsin (Try) affected by CeO 2 nanoparticles (NPs) were systematically studied via various spectroscopic methods. The results of fluorescence spectroscopy revealed that CeO 2 NPs markedly quenched the endogenous fluorescence of Try via the mechanism of static quenching. The main forces that contributed to the binding of Try and CeO 2 NPs were van der Waals forces, hydrogen bonds, and electrostatic forces, as observed by the binding constants and significant thermodynamic characteristics of the two substances. The incorporation of CeO 2 NPs lead to a slight change in the structure of Try, as shown by synchronized fluorescence spectroscopy, three-dimensional fluorescence spectroscopy and circular dichroism (CD) spectroscopy. Moreover, the enzyme activity of Try decreased with the addition of CeO 2 NPs. This study is highly important for fully evaluating the use of CeO 2 NPs in biomedical sciences and is helpful for clarifying the mechanism between Try and CeO 2 NPs at the molecular level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The reference values of eNO have certain differences among people of different countries and races. We aimed to obtain the reference value of eNO in healthy children and adolescents (6-18 years old) in China and to explore the associations between the reference values with ages, gender, heights, BMI, and regions., Methods: We measured FeNO 50 levels in 5949 healthy Chinese children and adolescents, FeNO 200 and CaNO levels in 658 participants from 16 provinces of 7 administrative areas in China aged 6-18. All persons were studied after obtaining informed consent from children and their parents., Results: The mean FeNO 50 of 5949 Chinese children and adolescents aged 6-18 years was 14.1 ppb, with a 95% confidence interval of 1-38.1 ppb. The mean FeNO 200 of 658 persons was 6.9 ppb with a 95% upper confidence interval of 15.0 ppb, and the mean CaNO was 3.0 ppb with a 95% upper confidence interval of 11.2 ppb. In the 6-11 age group, age and height were correlated with the logarithm of FeNO 50 (P < 0.001, P < 0.05). There was no significant correlation between the logarithm of FeNO 200 and gender, age, height and BMI (all P > 0.05). The logarithm of CaNO was correlated with gender (P < 0.05). In the 12-18 age group, gender, height, and region were correlated with the logarithm of FeNO 50 (all P < 0.001). There was only a weak correlation between the logarithm of FeNO 200 and height (P < 0.001). The logarithm of CaNO was negatively correlated with age (P < 0.05)., Conclusions: Higher FeNO 50 , FeNO 200 and CaNO values were found in healthy children and adolescents in China compared with foreign reports, and is affected by age, height, gender, and region. This study provides useful references for clinical application of eNO in children, especially Asian children., (© 2024. The Author(s).)

Background: Inflammation-related markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI) and prognostic nutritional index (PNI) could reflect tumor immune microenvironment and predict prognosis of cancers. However, it had not been explored in alpha-fetoprotein (AFP) producing gastric cancer (GC)., Aim: To determine the predictive value of inflammation-related peripheral blood markers including as NLR, PLR, MLR, SII, SIRI and PNI in the prognosis of AFP- producing GC (AFPGC). Besides, this study would also compare the differences in tumor immune microenvironment, clinical characteristics and prognosis between AFPGC and AFP- GC patients to improve the understanding of this disease., Methods: 573 patients enrolled were retrospectively studied. They were divided into AFP+ group (AFP ≥ 20 ng/mL) and AFP- group (AFP < 20 ng/mL), comparing the levels of NLR/PLR/MLR/SII/SIRI/PNI and prognosis. In AFP+ group, the impact of NLR/PLR/MLR/SII/SIRI/PNI and their dynamic changes on prognosis were further explored., Results: Compared with AFP- patients, AFP+ patients had higher NLR/PLR/MLR/SII/SIRI and lower PNI levels and poorer overall survival (OS). In the AFP+ group, mortality was significantly lower in the lower NLR/PLR/MLR/SII/SIRI group and higher PNI group. Moreover, the dynamic increase (NLR/PLR/MLR/SII/SIRI) or decrease (PNI) was associated with the rise of mortality within 1 year of follow-up., Conclusion: Compared with AFP- patients, the level of inflammation-related peripheral blood markers significantly increased in AFP+ patients, which was correlated with OS of AFP+ patients. Also, the gradual increase of SII and SIRI was associated with the risk of death within one year in AFP+ patients. AFPGC should be considered as a separate type and distinguished from AFP- GC because of the difference in tumor immune microenvironment. It requires basic experiments and large clinical samples in the future., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Vancomycin, a vital antibiotic for treating gram-positive bacterial infections, requires therapeutic drug monitoring (TDM) because of its substantial pharmacokinetic variability. While traditional TDM relies on steady-state trough concentrations, recent guidelines advocate the area under the concentration-time curve (AUC) as the target index. However, detailed protocols for AUC estimation are lacking, leading to potential discrepancies among institutions. We surveyed medical institutions in Korea regarding vancomycin TDM, including AUC estimation. Nineteen participants responded to the TDM case challenge under three patient scenarios. For an ordinary patient in Case 1, the overall CV for AUC values was 0.4% when both trough and peak concentrations were included in the AUC calculation and 1.9% when utilizing only the trough concentration. For Case 2, an older patient with obesity, the corresponding CV was 6.6%. For Case 3 with multiple trough concentrations, the CV was 15.6%, reflecting variations in the selective use of data. Although the agreements in Case 1 were good, significant variability in AUC estimation was noted in cases involving atypical patient characteristics or old TDM data. Our study provides insight into the current status of vancomycin TDM in Korea and underscores the need for standardized operational protocols for AUC estimation.

Objectives: ZR-202-CoV and ZR-202a-CoV are novel recombinant vaccines containing 25 µg of the prototype (Wuhan strain) or B.1.351 strain (Beta variant) SARS-CoV-2 S-protein expressed in CHO cells, respectively, adjuvanted with Al(OH) 3 and CpG-ODN. We assessed their safety and immunogenicity in this Phase I, randomized, observer-blind, controlled study in Mali., Design: Sixty healthy 18-55-year-old adults randomized 1:1:1 received two doses of ZR-202-CoV, ZR-202a-CoV, or Comirnaty Ⓡ 28 days apart. Primary outcome measures were solicited and unsolicited adverse events (AEs) including AESI (Adverse Events of Special Interest); secondary outcome was immunogenicity measured as SARS-CoV-2 specific neutralizing antibodies. Participants were followed up for 1 year., Results: Injection site pain and headache were the most frequent solicited local and systemic AEs, respectively. No unsolicited AEs or SAEs related to vaccination were reported during the study period. Although most participants had detectable neutralizing antibodies at baseline robust immune responses were observed in all vaccine groups after the first dose with no further increase after the second dose. Cross-neutralizing antibody responses against Beta, Delta, and Omicron BA.5 variants were similar in magnitude after ZR-202-CoV, ZR-202a-CoV and Comirnaty Ⓡ ., Conclusions: Similar reactogenicity and immunogenicity profiles of ZR-202-CoV, ZR-202a-CoV and Comirnaty Ⓡ support further clinical investigation in a wider population., Competing Interests: Declarations of competing interest The authors declare the following competing interests: Min Ji, Xi Han, and Chenliang Zhou are employees of Shanghai Zerun Biotechnology Co., Ltd. All other authors report no potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diabetes can involve several ocular structures -- including the cornea, lens, and retina -- and cause vascular and neural changes in these tissues. Although retinopathy is the most common ocular complication of diabetes, uveopathy can also be observed. This includes vascular, neural, muscular, and basement membrane changes. The main clinical manifestations of diabetic uveopathy are anterior uveitis and abnormal pupillary dynamics. Fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography are ideal for the imaging of vascular changes of the iris and choroid, while dynamic pupillometry is a simple screening tool to detect neuropathy. Additionally, ultrasound biomicroscopy can provide clear images of the ciliary body. Iris abnormalities, primarily angiopathy and neuropathy, can appear as alterations in vascular diameter, neovascularization, and abnormal pupillary dynamics. Choroidal abnormalities primarily affect blood vessels, including alterations in vascular diameter, microaneurysm formation, and neovascularization. The abnormal manifestations in the ciliary body include a decrease in vessel count, alterations in their diameter, isolated angiomatous dilatation, and diffuse thickening of the basal membrane of the pigment epithelium., 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.)

Enzyme-catalyzed chemiluminescence has been widely used in the field of biomedicine, especially in the test kit for various biomarkers. However, the currently reported enzyme-catalyzed chemiluminescence systems suffered from the addition of oxidizing substances, short emission wavelength, and susceptibility to interference by autofluorescence. In this paper, a universal sulfatase-based chemiluminescence system with NIR was developed, in which the designed substrate QM-CF could be transformed into 1,2-dioxetane derivate in the presence of sulfatase and oxygen. This system exhibited long emission wavelengths and CL half-time, a high signal-noise ratio, and without other additives. Importantly, the sulfatase-based chemiluminescence enzyme-linked immunoassay platform was successfully constructed and could be generally applied to detect biomarkers. As a proof of concept, the sulfatase-labeled AFP antibody and substate QM-CF were conveniently suitable for commercial AFP test kits, leading to satisfactory detection results of AFP in clinical blood samples., 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.)

Purpose: This study aimed to assess whether assisted reproductive technology alters DNA methylation levels at the H19 promoter and H19 imprinting control element (ICE) in fetal tissues obtained after multifetal pregnancy reduction., Methods: Fetal tissues from multiple pregnancies were obtained, including fresh and frozen-thawed embryos: nine from conventional in vitro fertilization (c-IVF), four from intracytoplasmic sperm injection (ICSI), ten from cryopreserved IVF embryos (cryo-IVF), and six from cryopreserved ICSI (cryo-ICSI) embryos. Next-generation sequencing-based bisulfite PCR was used to determine the DNA methylation status of three CpG islands (H19-1, H19-2, and H19-3) in the H19 promoter and H19 ICE. The primary outcome was H19-1 DNA methylation status, whereas secondary outcomes assessed H19-2, H19-3, and ICE methylation., Results: The ICSI (β = -3.189, 95% CI = -5.034 to -1.345, p = 0.0026), cryo-IVF (β = -2.150, 95% CI = -3.706 to -0.593, p = 0.0129), and cryo-ICSI (β = -2.238, 95% CI = -3.817 to -0.659, p = 0.0110) groups exhibited significantly lower methylation levels in the primary outcome H19-1 region than the c-IVF group after adjustment. For the secondary outcome H19-2 region, significant decreases were observed in the cryo-IVF (β = -2.132, 95% CI = -4.071 to -0.192, p = 0.0425) and cryo-ICSI groups (β = -2.598, 95% CI = -4.566 to -0.630, p = 0.0168)., Conclusions: These findings further indicate that embryo cryopreservation and potentially ICSI can lower the methylation level of the H19 promoter, advocating for careful use of these techniques when necessary., (© 2024. The Author(s).)

Stratification strategies for chemotherapy plus PD-1 inhibitors in advanced non-small-cell lung cancer (NSCLC) are critically demanded. We performed high-throughput panel-based deep next-generation sequencing and low-pass whole genome sequencing on prospectively collected circulating tumor DNA (ctDNA) specimens from 460 patients in the phase 3 CHOICE-01 study at different time points. We identified predictive markers for chemotherapy plus PD-1 inhibitor, including ctDNA status and genomic features such as blood-based tumor mutational burden, intratumor heterogeneity, and chromosomal instability. Furthermore, we established an integrated ctDNA-based stratification strategy, blood-based genomic immune subtypes (bGIS) scheme, to distinguish patients who benefit from the addition of PD-1 inhibitor to first-line chemotherapy. Moreover, we demonstrated potential applications for the dynamic monitoring of ctDNA. Overall, we proposed a potential therapeutic algorithm based on the ctDNA-based stratification strategy, shedding light on the individualized management of immune-chemotherapies for patients with advanced NSCLC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Yes-associated protein (YAP) is a central player in cancer development, with functions extending beyond its recognized role in cell growth regulation. Recent work has identified a link between YAP/transcriptional coactivator with PDZ-binding motif (TAZ) and the DNA damage response. Here, we investigated the mechanistic underpinnings of the cross-talk between DNA damage repair and YAP activity. Ku70, a key component of the nonhomologous end joining pathway to repair DNA damage, engaged in a dynamic competition with TEAD4 for binding to YAP, limiting the transcriptional activity of YAP. Depletion of Ku70 enhanced interaction between YAP and TEAD4 and boosted YAP transcriptional capacity. Consequently, Ku70 loss enhanced tumorigenesis in colon cancer and hepatocellular carcinoma (HCC) in vivo. YAP impeded DNA damage repair and elevated genome instability by inducing PARP1 degradation through the SMURF2-mediated ubiquitin-proteasome pathway. Analysis of samples from patients with HCC substantiated the link between Ku70 expression, YAP activity, PARP1 levels, and genome instability. In conclusion, this research provides insight into the mechanistic interactions between YAP and key regulators of DNA damage repair, highlighting the role of a Ku70-YAP-PARP1 axis in preserving genome stability. Significance: Increased yes-associated protein transcriptional activity stimulated by loss of Ku70 induces PARP1 degradation by upregulating SMURF2 to inhibit DNA damage, driving genome instability and tumorigenesis., (©2024 American Association for Cancer Research.)

Oesophageal squamous cell carcinoma (ESCC) contributes to high mortality. Modulating ferroptosis may reverse resistance to radiotherapy. This article was to explore the ubiquitination modification of KLF5 and its effect on ferroptosis in ESCC. KLF5 was under-expressed by shRNA plasmids in the cells and ROS levels were analysed by flow cytometry, ferroptotic gene expression was detected by qRT-PCR, MDA and GSH levels were determined by ELISA, cell morphology was observed by transmission electron microscopy, and Fe ion levels were analysed by immunofluorescence. Cells were treated with Ferrostatin-1 and NAC and analysed for cell proliferation by colony formation assay, cell migration and invasion by Transwell assays, and apoptosis by flow cytometry. DNA damage in cells was also analysed using comet assay, EdU doping assay, γH2AX fluorescence, DNA-PKcs and PCR. NEDD4L and KLF5 binding was analysed by immunoprecipitation. Changes in ferroptosis, DNA damage and resistance were analysed in cells with both silencing NEDD4L and KLF5. Changes in tumour resistance to radiation were analysed in mice underexpressing NEDD4L and KLF5. Low expression of KLF5 significantly promotes cellular lipid peroxidation levels, with decreased expression of SOD and GPX4, and increased expression of ACSL4. Concurrently, MDA levels deplete GSH, and cells exhibit typical ferroptotic morphology with increased Fe2+ content. KLF5 inhibition results in enhanced cellular clonogenicity, migration and invasion activities, reduced apoptosis, increased tail DNA, nuclear EdU incorporation, nuclear γH2AX foci and elevated expression of DNA-PKcs, LIG4, RAD9B and BMI1. Ferrostatin-1 and NAC reverse these effects. NEDD4L ubiquitination modifies and degrades KLF5, with NEDD4L/KLF5 inhibition mitigating cellular ferroptosis and DNA damage, thereby promoting radiosensitivity both in vitro and in vivo. NEDD4L increases radiosensitivity by accelerating cellular ferroptosis via ubiquitination modification of KLF5., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)