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Substantial advancements have been made in recent years in comprehending immune memory, which enhances the secondary response through prior infections. The ability of vertebrate T and B lymphocytes to exhibit classic recall responses has long been regarded as a distinguishing characteristic. However, natural killer (NK) cells have been found to acquire immunological memory in a manner akin to T and B cells. The fundamental principles derived from the investigation of NK cell memory offer novel insights into innate immunity and have the potential to pave the way for innovative strategies to enhance therapeutic interventions against multiple diseases including cancer. Here, we reviewed the fundamental characteristics, memory development and regulatory mechanism of NK cell memory. Moreover, we will conduct a comprehensive evaluation of the accomplishments, obstacles, and future direction pertaining to the utilization of NK cell memory in the field of cancer immunotherapy.

Fibroblasts undergo metabolic reprogramming after contact with cancer cells in tumor microenvironment, producing lactate to provide a metabolic substrate for neighboring tumor cells. The exchange of lactate between cancer cells and fibroblasts via monocarboxylate transporters (MCTs) is known as the lactate shuttle. Colorectal cancer cells may establish a metabolic coupling akin to the lactate shuttle in collaboration with cancer-associated fibroblasts (CAFs) to augment their invasive and migratory capabilities. However, the specific phenomena and underlying mechanisms are not clear. In this study, we investigated the phenomena and explored the correlation and possible mechanism between CAFs and the invasion and migration of colorectal cancer cells by using two different co-culture models. The results showed that colorectal cancer cells established a lactate metabolic coupling with fibroblasts through the oxidative stress effect, triggering the metabolic reprogramming process of themselves and those of fibroblasts. In addition, lactate enhanced the invasion and migration of colorectal cancer by stabilizing the protein expression levels of nuclear factor kappa-B (NF-κB) and hypoxia-inducible factor-1α (HIF-1α). Blocking oxidative stress and lactate metabolic coupling with reactive oxygen species removers and MCT1-specific inhibitors, respectively, could effectively suppress metastasis in colorectal cancer. These findings suggest that targeting the lactate metabolic coupling between tumor cells and CAFs will offer a new strategy to combat colorectal cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Chordoma is a rare and aggressive bone tumor with high-recurrence and lack of effective treatment methods. Tumor associated macrophages (TAMs) are abundant in tumor microenvironment (TME) and polarize toward M2 in chordoma. It has been observed that the high proportion of M2 cells is associated with chordoma rapid progression. However, the mechanism of TAMs polarization and promotion to tumor progression in chordoma is still unclear. The is an urgent need for further research., Materials and Methods: Flow cytometry and immunohistochemical staining was used to detect the degree of macrophages infiltration in chordoma. A co-culture model of chordoma cells and macrophages was established in vitro to investigate the effects of their interaction on cell function, cytokine secretion, and RNA transcriptome expression., Key Findings: In this study, we found M2 macrophage was predominantly abundant immune cell population in chordoma, and its proportion was associated with the degree of bone destruction. We demonstrated that interleukin 6 (IL-6) derived from chordoma cells could induce TAMs polarization by activating STAT3 phosphorylation, and TAMs could enhance chordoma cells migration and invasion through TNFα/NF-κB pathway. The interaction of chordoma cells and TAMs could promote the bone destruction-related factor Cathepsin B (CTSB) and inhibitory immune checkpoints expression. We also confirmed blocking IL-6/STAT3 pathway could significantly attenuate the M2 polarization of TAMs and decrease the secretion of TNFα., Significance: This study illustrates the dynamics between chordoma cells and TAMs in promoting chordoma invasion and suggests that IL-6/STAT3 pathway is a potential therapeutic target to reduce TAM-induced chordoma invasion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Emergency management of municipal solid waste during public health emergencies is crucial for curbing the spread of viruses and controlling environmental pollution. Most existing solid waste management systems, are designed with a top-down approach, covering multiple industries and sectors. However, these systems often fail to effectively manage potentially viral solid waste in household waste, which impedes effective solid waste management during public health emergencies and increases the risk of viral outbreaks. For example, during the COVID-19 outbreak, negligent management of potentially viral solid waste may result in the formation of a potential transmission chain of COVID-19 virus. Improper waste management may contaminate natural vectors such as water, soil and air, thereby increasing the pathways of human contact with infected vectors and promoting the risk of transmission of viral diseases such as dengue, Zika and hepatitis A. In this study, the applicability and limitations of the Chinese public emergency management system in the disposal of Potentially Viral/Viral Municipal Solid Waste (PVMSW) were analyzed in the breakout of public health crises. To address the need for precise risk control, efficient collaboration among key stakeholders, functional integration crossing multiple management organizations and flexible responses to complex situations, we proposed a PVMSW emergency management system based on a "Beam-Column Structure" model. This system consists of four modules: main traction, organizational leadership, functional articulation and demand matching. Each module is supported by the corresponding safeguards, including multi-level subject responsibilities, multi-scenario organization and implementation, multi-chain process connection and multi-demand control methods. The PVMSW emergency management system proposed in this study contributes to extending the framework of existing waste management protocols and enhancing the timely collection, transportation and disposal of PVMSW in public health crises. It offers valuable insights and guidance on the practices for improving risk awareness and management capacity in China's solid waste emergency response., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ying Li reports financial support was provided by The Cultivation project Funds for Beijing University of Civil Engineering and Architecture. Ying Li reports financial support was provided by Beijing Municipal Education Commission. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Air quality models are increasingly important in air pollution forecasting and control. Sectoral emissions significantly impact the accuracy of air quality models and source apportionment. This paper studied the 3DVar (three-dimensional variational) emission inversion method, which is based on machine learning, and then expanded it to sectoral emission inversion combined with source apportionment. Two machine learning conversion matrices were established to implement this method: a matrix that converts the total pollutant concentration to sectoral source apportionment results and a matrix that converts the sectoral source apportionment results to corresponding emissions. Combined with the O 3 (ozone) concentration contributed by VOCs (volatile organic compounds) and NO x (nitrogen oxides) precursors in source apportionment, the inversion ability for O 3 -NO x -VOCs nonlinear processes was improved. Taking the BTH (Beijing‒Tianjin-Hebei) region from January 15 to 30, 2019, as an example, the results revealed that the regional errors of PM 2.5 and O 3 in the inversion experiment were reduced by 47% and 45%, respectively, and the temporal errors were reduced by 44% and 16%, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Chronic restrain stress (CRS) induces depression-like behaviors and demyelination in the brain; however, the relationship between these depression-like behaviors and demyelination remains unclear. Arketamine, the (R)-enantiomer of ketamine, has shown rapid antidepressant-like effects in CRS-exposed mice., Methods: We examined whether arketamine can improve both depression-like behaviors and demyelination in the brains of CRS-exposed mice. Additionally, we investigated the role of transforming growth factor β1 (TGF-β1) in the beneficial effects of arketamine., Results: A single dose of arketamine (10 mg/kg) improved both depression-like behavior and demyelination in the corpus callosum of CRS-exposed mice. Correlations were found between depression-like behaviors and demyelination in this region. Furthermore, pretreatment with RepSox, an inhibitor of TGF-β1 receptor, significantly blocked the beneficial effects of arketamine on depression-like behaviors and demyelination in CRS-exposed mice. Finally, a single intranasal administration of TGF-β1 ameliorated both depression-like behaviors and demyelination in CRS-exposed mice., Limitations: The precise mechanisms by which TGF-β1 contributes to the effects of arketamine remain unclear., Conclusions: These data suggest that CRS-induced demyelination in the corpus callosum may contribute to depression-like behaviors, and that arketamine can mitigate these changes through a TGF-β1-dependent mechanism., Competing Interests: Declaration of competing interest Dr. Hashimoto is the inventor of filed patent applications on “The use of R-ketamine in the treatment of psychiatric diseases”, “(S)-norketamine and salt thereof as pharmaceutical”, “R-ketamine and derivative thereof as prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder”, “Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases”, and “R-ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder” by the Chiba University. Dr. Hashimoto has also received speakers' honoraria, consultant fee, or research support from Otsuka. Other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The metabolic disorders in the purine degradation pathway have proven to be closely associated with several human diseases. However, the etiology is not yet fully understood. Profile assay of purine intermediates and uric acid involved in the metabolic pathway can provide additional insight into the nature and severity of related diseases. Purine metabolites are endogenous chemicals with high hydrophilicity, polarity, and similar structures, thus there is a great need for a specific method to quantify them directly in biological fluids with a short running time. Herein, eight purine degradation pathway metabolites, including xanthine, hypoxanthine, guanine, xanthosine, inosine, guanosine, adenosine and uric acid, in human plasma were quantitatively measured using hydrophilic interaction chromatography-tandem high-resolution mass spectrometry (HILIC-HRMS) in a short running time of 10 min. The method was systematically validated for specificity, linearity of the calibration curve, the limit of detection, the limit of quantification, the lower limit of quantification, precision, accuracy, extraction recovery, matrix effect, and stability. The results showed that the method was linear (R 2 > 0.99), accurate (the intra- and inter-day recoveries of all analytes ranged from 90.0 % to 110.0 %), and precise (the intra- and inter-day precisions were less than 6.7 % and 8.9 %, respectively) with the lower limits of quantification ranging from 3 to 10,000 ng/mL. The extraction recoveries and matrix effects were repeatable and stable. All the analytes were stable in the autosampler and could be subject to three freeze-thaw cycles. The developed method was ultimately applied to 100 plasma specimens from healthy individuals. The results showed that the concentrations of different purine metabolites varied dramatically in plasma specimens. Diet and body mass index (BMI) were the most significant factors determining purine levels, followed by drinking and sex. Age, smoking and bedtime showed a very weak correlation with purine metabolism. The findings of the present work reveal the characteristics of purine metabolism in human plasma under non-pathological conditions. The results also highlight the factors that can cause changes in purine metabolism, which are useful in developing effective treatment strategies for metabolic disorders of purines, particularly for those caused by lifestyle factors., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ronghua Fan reports financial support was provided by Scientific Research Project of the Department of Science and Technology of Liaoning Province. Ronghua Fan reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Elderly stable chronic obstructive pulmonary disease (COPD) patients frequently experience walking dysfunction. Research indicates that balance training holds promise for enhancing walking stability in these individuals, whereas respiratory therapy (RT) can enhance walking endurance effectively. However, existing balance training regimens tailored for COPD are intricate and lack specificity, and the impact of combined RT on patients' walking function remains uncertain. This study aims to assess the influence of core training (CT) integrated with RT on walking function among elderly stable COPD patients., Methods and Analysis: This randomised, assessment-blinded, routine rehabilitation-controlled trial will be carried out at the Department of Respiratory and Critical Care Rehabilitation, the Second Rehabilitation Hospital of Shanghai. A total of 42 elderly patients diagnosed with stable COPD will be randomly allocated to either the study group (SG) or the control group in a 1:1 ratio. Both groups will undergo 6 weeks of standard rehabilitation training. Additionally, patients in the SG will receive CT based on RT. The primary outcome of the study is the 6 min walk test. Secondary outcomes encompass ultrasound indicators of the diaphragm and multifidus, pulmonary function tests, Berg balance scale test, trunk impairment scale test, COPD assessment test and St. George's Respiratory Questionnaire., Ethics and Dissemination: Ethical approval was obtained from the Ethics Committee of the Second Rehabilitation Hospital of Shanghai (2023-01-01, see online supplemental file 1). All patients will provide written informed consent before participation. The results of the trial are intended for publication in a peer-reviewed journal., Trial Registration Number: ChiCTR2400080276., 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.)

Background: Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT., Methods: We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals. Serum GFAP and UCH-L1 levels were measured 24 hours after IVT. Cases from 1 hospital were randomly assigned to the training (70%) and testing (30%) cohorts for internal validation. The external validation cohort included patients from the other 15 hospitals. Cutoff levels of GFAP and UCH-L1 for assessing the absence of HT were established in the training cohort and subjected to internal and external verification., Results: A total of 1063 patients were included. Both GFAP and UCH-L1 levels were independently associated with HT, infarct volume, and 3-month outcome; levels lower than cutoff (12.6 and 63.1 pg/mL, respectively) excluded patients with HT with a negative predictive value of 98.31% (95% CI, 89.70%-99.91%) and detection sensitivity of 98.08% (95% CI, 88.42%-99.90%) in the training cohort. In the testing and validation cohorts, negative predictive value was 100% (95% CI, 75.93%-100%) and 100% (95% CI, 82.19%-100%), respectively, and the sensitivity was 100% (95% CI, 80.76%-100%) and 100% (95% CI, 77.08%-100%), respectively., Conclusions: Serum GFAP and UCH-L1 levels exhibit high sensitivity and negative predictive value for indicating the absence of HT 24 hours after IVT, which supports their potential role in assessing patients' condition after IVT.

Epidermal growth factor receptor (EGFR) is a starring target for the treatment of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) have been used to treat NSCLC patients with EGFR-activating mutations. However, most patients invariably develop resistance to these agents due to the occurrence of novel mutations at the EGFR kinase domain. There is an urgent need to develop more effective therapy strategies to provide more selection for patients with NSCLC. Coccinic acid was reported to exerts potential anti-tumor effects, but its mechanism has not been elucidated and warrants investigation. In this study, coccinic acid was shown to inhibit cell proliferation on cells harboring L858R/T790M mutant EGFR by suppressing p-EGFR and p-STAT3. It was also shown that coccinic acid promoted cell cycle distribution and showed a potent apoptosis-inducing efficacy. Further results in vivo assays demonstrated that coccinic acid reduced tumor growth of NCI-H1975 xenograft in nude mice via the EGFR/STAT3 signaling. Moreover, these effects are involving in the binding of coccinic acid to the EGFR extracellular domain. In conclusion, our finding demonstrated that coccinic acid may be utilized as a potential novel candidate for NSCLC with EGFR L858R/T790M mutation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Retinal sublayer thickness is associated with both ophthalmic and neurodegenerative diseases, serving as a valuable biomarker. Despite the established role of diet in chronic disease prevention, the relationship between healthy dietary patterns and retinal sublayer thickness remains underexplored., Objective: This study aims to investigate the associations between four commonly used diet assessment scores and retinal sublayer thickness in a large-scale population., Methods: This study utilized data from the UK Biobank, including 13,993 participants with complete optical coherence tomography (OCT) measurements and dietary assessments. The dietary patterns analyzed were the Alternate Mediterranean Diet (AMED), Anti-Empirical Dietary Inflammatory Index (AEDII), Alternate Healthy Eating Index-2010 (AHEI-2010), and Healthful Plant-Based Diet Index (HPDI). Retinal sublayers measured included macular retinal nerve fiber layer (mRNFL), macular ganglion cell-inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC), retinal pigment epithelium (mRPE), the outer nuclear layer of the central subfield (ONL), photoreceptor inner segment of the central subfield (IS) and total macular thickness. Multivariable linear regression models adjusted for demographics, ophthalmic measurements, and lifestyle factors were employed to examine associations. Mediation analysis was applied to explore the potential mediation effect of several blood biochemical indicators in simple mediation models., Results: Higher HPDI scores were significantly associated with increased central retinal macular thickness (β = 0.106, p = 0.001), mGCIPL thickness (β = 0.017, p = 0.033), mRPE (β = -0.012, p = 0.161), ONL (β = 0.044, p = 0.003), IS (β = 0.003, p = 0.005) and mGCC thickness (β = 0.027, p = 0.025). In contrast, the AMED, AEDII, and AHEI-2010 scores did not show consistent associations with retinal sublayer thickness except ONL and IS. The mediation analysis revealed that cholesterol acted as a suppressor variable, partially mediating the relationship between HPDI and retinal sublayer thickness. Sensitivity analyses indicated that the associations between HPDI and retinal sublayer thickness were more pronounced in younger individuals and females. Additionally, the variability in associations across different age and sex subgroups highlighted the potential influence of demographic factors on dietary impacts., Conclusion: The study findings suggest that adherence to a healthful plant-based diet may confer neuroprotective benefits, particularly for retinal ganglion cell health. This large-scale population-based study underscores the potential role of diet in mitigating early neurodegenerative changes detectable through non-invasive retinal imaging. Further longitudinal research is needed to establish causal relationships and elucidate the underlying mechanisms between diet and retinal health., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Inflammation is hypothesized to have essential functions in the development of wet age-related macular degeneration (AMD). Polymorphonuclear neutrophils (PMNs), recognized as major players in inflammation, are typically the first leukocytes to be recruited to an inflammatory site. Previous studies have identified neutrophil aggregates in the lesion site of the choroidal neovascularization model, and systemic depletion of neutrophils in adult mice is associated with reduced choroidal neovascularization (CNV) area, suggesting a pivotal role of PMNs in CNV pathogenesis. Here, we investigate the role of neutrophils in promoting CNV, a key feature of wet AMD. The malfunction and demise of retinal pigment epithelium cells are essential elements in CNV pathogenesis. Our hypothesis posits that neutrophils exacerbate CNV by influencing pro-inflammatory cytokines secreted by retinal pigment epithelium (RPE) cells. Using in vivo laser-induced CNV models with mice and in vitro experiments with the human ARPE-19 cell line, we demonstrated that co-culturing neutrophils with ARPE-19 cells induces an increase in pro-inflammatory cytokines and leads to S-phase cell cycle arrest, potentially through the induction of double-strand breaks (DSBs). Further exploration of this interaction revealed a potential pathway involving reactive oxygen species (ROS) and microRNA-23a, wherein PMNs induce DSBs by initiating the downregulation of LB1 via microRNA-23a. Additionally, we found that dHL-60 cell line could serve as a substitute for primary PMNs, highlighting its potential as a valuable tool in experimental models involving interactions with retinal cells. Our findings underscore the significant role of neutrophils in CNV pathogenesis, providing insights into potential therapeutic targets for wet AMD., 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.)

Hypertension-induced myocardial remodelling encompasses both structural and functional changes in cardiac muscle tissue, such as myocardial hypertrophy, fibrosis, and inflammation. These alterations not only impair the systolic and diastolic functions of the heart but also elevate the risk of cardiovascular events and heart failure. One of the primary contributors to hypertensive cardiomyopathy (HTN-CM) is the over-activation of the renin-angiotensin-aldosterone system (RAAS), which subsequently induces myocardial remodeling. Although conventional therapeutic strategies aim to suppress RAAS and slow the progression of heart failure, the primary challenge in treating HTN-CM remains the lack of sensitive and specific biomarkers for early detection of myocardial remodelling. Combined multi-omics analyses, complemented by experimental validation, offer a systematic understanding of the landscape of gene/protein/metabolite expression in HTN-CM, revealing the underlying mechanisms of angiotensin II (Ang II)-induced myocardial remodeling in HTN-CM. Transcriptomic analysis revealed that differentially expressed genes (DEGs) are implicated in sphingolipid metabolic processes and are associated with collagen synthesis and inflammatory responses, collectively contributing to myocardial remodeling in HTN-CM. Proteomic analysis demonstrated that differentially expressed proteins (DEPs) are also involved in inflammatory and fibrotic processes, with associations to sphingolipid signaling pathways, particularly manifested through elevated expression of IL6, COL4A1, FGG, FGB, CREBBP and SPHK2 proteins. Metabolomic profiling further elucidated the increased expression of bioactive sphingolipid metabolites S1P and Sa1P in the myocardium of HTN-CM. Integrative multi-omics analysis revealed that HTN-CM is primarily influenced by the sphingolipid signaling pathway, with additional associations to the HIF-1α and FoxO signaling pathways. Correlation analysis has highlighted strong associations between sphingolipids and genes/proteins related to fibrosis and inflammation, as well as their connection to the HIF-1α and FoxO signalling pathways. Furthermore, certain key indicators were validated through ELISA and Western blot analyses in both plasma and myocardial tissue. In conclusion, the findings of this study suggest that excessive Ang II may induce abnormalities in sphingolipid metabolism, resulting in increased levels of S1P in both circulating and myocardial tissues. This elevation in S1P is implicated in myocardial inflammatory and fibrotic alterations, highlighting its pivotal role in myocardial remodeling. The specific mechanism underlying the sphingolipid signaling pathway in myocardial remodeling may involve downstream biological processes, including oxidative stress and excessive mitochondrial autophagy, mediated by HIF-1α and FoxO., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The nicotinamide adenosine dinucleotide-dependent deacetylase Sirtuin 1 (SIRT1) has been identified as a protective factor that inhibits the activation of nucleotide-binding and oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome. However, whether pharmacological SIRT1 activators can protect retinal pigment epithelial (RPE) cells against oxidative and inflammatory injuries related to age-related macular degeneration remains to be explored., Methods: Two small molecule specific SIRT1 activators (SRT2104 and CAY10602) were tested, with resveratrol being used as a positive control. Mouse models with sodium iodate-induced retinal degeneration were constructed. ARPE-19 cells in culture were used for in vitro experiments. The effects of SIRT1 activators on H 2 O 2 -induced ARPE-19 cell injury were determined by reactive oxygen species quantification, western blotting, flow cytometry and immunofluorescence staining. In vivo, the severity of retinal damage was assessed using flash electroretinography and histopathological analysis., Results: In vitro, SRT2104, CAY10602 and resveratrol significantly attenuated H 2 O 2 -induced cell death, nucleolar stress response, and reactive oxygen species accumulation. In H 2 O 2 -stimulated cells, SIRT1 activators reduced the level of NLRP3, inhibited the activation of caspase-1, and decreased the production of interleukin (IL)-1β and IL-18. The inhibitory effects of SIRT1 activators on caspase-1 activation and IL-1β production were blunted by SIRT1 gene silencing. In vivo, treatment with SRT2104 or CAY10602 in mice with sodium iodate-induced retinal degeneration markedly improved the retinal functions and reduced the loss of RPE cells., Conclusion: Our study suggests that small molecule SIRT1 activators are effective for protection of RPE cells against oxidative stress-induced NLRP3 inflammasome activation, highlighting potential applications in the treatment of macular degeneration associated RPE dysfunctions., 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: To evaluate the safety and efficacy of neoadjuvant immunotherapy in patients with esophageal squamous cell carcinoma (ESCC) and construct a prognostic model., Methods: Clinical data were retrospectively collected from patients with locally advanced ESCC who received neoadjuvant immunotherapy and chemotherapy. The primary endpoints were major pathologic remission rate and disease-free survival, and secondary endpoints were treatment-related adverse events and perioperative complications. Correlates affecting pathological response were analyzed using univariate and multivariate logistic regression, survival-related variables were screened by Boruta and least absolute shrinkage and selection operator Cox regression analysis. A nomogram was constructed and utilized to test the predictive efficacy of the treatment with receiver operating characteristic curve and decision curve analysis., Results: A total of 181 patients were enrolled, of whom 119 (66 %) patients received 3-4 cycles of treatment. Treatment-related adverse events occurred in 65.2 % of the patients, with 13.3 % experiencing severe complications. Major pathological remission rate was achieved in 68 (37.6 %) patients, with no significant difference between the treatment cycle groups (P=0.925). The nomogram included pathologic TNM stage, lymphovascular invasion, post-treatment and post-surgery albumin levels, and post-treatment systemic immune-inflammation index. One-year disease-free survival area under the curve was 0.86 (95 %CI, 0.75-0.97) in the derivation cohort and 0.75 (95 %CI, 0.50-0.99) in the validation cohort, with good calibration performance., Conclusions: Pathological staging combined with albumin level and systemic immune-inflammation index could be a superior predictor of survival prognosis in ESCC patients receiving neoadjuvant immunotherapy. The findings of this study yield new evidence regarding the efficacy and safety of neoadjuvant immunotherapy in ESCC and provide a tool for identifying patients at risk of recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

SIRT6 promotes the progression of breast cancer by inducing drug resistance by reinforcing DNA damage repair mechanisms. This study utilized a combination of high-throughput virtual screening and FLUOR DE LYS assays. Hit 14 which features a novel β-carboline skeleton as a potent SIRT6 inhibitor was found. Subsequent structure-guided optimization led to the synthesis of 60 3,6,9-position modified derivatives based on the differences analysis of SIRTs family proteins. Of which, 10d inhibited the deacetylase activity of SIRT6, with an IC 50 of 5.81 μM and more than 27 times subtype selectivity. Phe64, Met157, and Ser56 were identified as the key residues. Moreover, 10d suppressed breast cancer cell proliferation, migration, invasion, and induced apoptosis in MCF-7 cells by disrupting the DNA damage repair pathway. Additionally, 10d demonstrated a safe and effective antibreast cancer effect in vivo , presenting a promising strategy for the treatment of breast cancer by targeting SIRT6.

Ocean acidification, a major consequence of climate change, poses significant threats to marine organisms, particularly when combined with other environmental stressors such as chemical pollution. This study investigated the physiological responses of Trochus niloticus to a 28-day exposure of ocean acidification and/or sulfamethoxazole, a commonly detected antibiotic in the South China Sea. Exposure to either acidification or sulfamethoxazole individually triggered adaptive responses through immune activation, antioxidant reactions, and metabolic adjustments. However, concurrent exposure resulted in significant adverse effects, including compromised immunity, oxidative damage, and disrupted energy budget. These findings provide new insights into how ocean acidification interacts with antibiotic pollution to synergistically impact marine gastropods, suggesting that multiple stressors may pose greater threats to T. niloticus populations than single stressors alone., 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.)

Parthanatos is distinct from caspase-dependent apoptosis in that it does not necessitate the activation of caspase cascades; Instead, it relies on the translocation of Apoptosis-inducing Factor (AIF) from the mitochondria to the nucleus, resulting in nuclear DNA fragmentation. Newcastle Disease Virus (NDV) is an oncolytic virus that selectively targets and kills tumor cells by inducing cell apoptosis. It has been reported that NDV triggers classic apoptosis through the mitochondrial pathway. In this study, we observed that NDV infection induced endoplasmic reticulum stress (ERS), which caused a rapid release of endogenous calcium ions (Ca2+). This cascade of events resulted in mitochondrial depolarization, loss of mitochondrial membrane potential, and structural remodeling of the mitochondria. The overload of Ca2+ also initiated an increase in mitochondrial membrane permeability, facilitating the transfer of AIF to the nucleus to induce apoptosis. Damaged mitochondria produced excessive reactive oxygen species (ROS), which further exacerbated mitochondrial damage and increased mitochondrial membrane permeability, thus promoting additional intracellular Ca2+ accumulation and ultimately triggering an ROS burst. Collectively, these findings indicate that NDV infection promotes excessive calcium accumulation and ROS generation, leading to mitochondrial damage that releases more calcium and ROS, creating a feedback loop that exacerbates AIF-dependent parthanatos. This study not only provides a novel perspective on the oncolytic mechanism of NDV but also highlights new targets for antiviral research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Qu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although astrocytes undergo functional changes in response to brain injury and may be the driving force of subsequent neuronal death, the underlying mechanisms remain incompletely elucidated. Here, we showed that extracellular vesicle (EV)-shuttled miRNA-382-5p may serve as a biomarker for the severity of traumatic brain injury (TBI), as the circulating EV-miRNA-382-5p level was significantly increased in both human patients and TBI model mice. Mechanistically, astrocyte-derived EVs delivered the shuttled miRNA-382-5p to mediate astrocyte-neuron communication, which promoted neuronal mitochondrial dysfunction by inhibiting the expression of optic atrophy-1 (OPA1). Consistent with these findings, genetic ablation of neuronal OPA1 exacerbated mitochondrial damage and neuronal apoptosis in response to TBI. Moreover, engineered RVG-miRNA-382-5p inhibitor-EVs, which can selectively deliver a miRNA-382-5p inhibitor to neurons, significantly attenuated mitochondrial damage and improved neurological function after TBI. Taken together, our data suggest that EV-shuttled miRNA-382-5p may be a critical mediator of astrocyte-induced neurotoxicity under pathological conditions and that targeting miRNA-382-5p-OPA1 signaling has potential for clinical translation in the treatment of traumatic brain injury., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Colorectal cancer continues to be a major health issue even though screening methods have facilitated early detection. Despite the high sensitivity of white-light colonoscopy, it frequently overlooks invasive flat or depressed lesions, which can lead to the development of larger, advanced tumors. Fluorescence molecular imaging offers a promising approach for early tumor detection by targeting specific molecular characteristics of lesions. CD24 is upregulated during the adenoma-to-colorectal cancer transition, providing a potential target for fluorescence molecular imaging. In this study, we developed a second near-infrared window (NIR-II) fluorescent probe with a high affinity for CD24 and evaluated its efficacy and targeting ability in cellular models, murine models, and clinical samples of colorectal cancer. CD24 expression was elevated in 76% of adenomas and 80% of colorectal cancers. In a colitis-associated cancer mouse model, NIR-II imaging with the CD24-targeted probe achieved a significantly higher tumor-to-background ratio compared with conventional NIR-I imaging. The probe demonstrated exceptional sensitivity (92%) and specificity (92%) for detecting colorectal cancer, including small lesions less than 1 mm in size. This led to the identification of precancerous lesions missed by white-light detection and lesions missed by NIR-I imaging. Moreover, ex vivo human tissue incubation with the probe supported the potential for intraprocedural lesion identification via topical probe application during colonoscopy. In conclusion, this study successfully demonstrates the potential of CD24-targeted NIR-II imaging for identifying colorectal neoplasia, highlighting its significance for early colorectal cancer detection in the gastrointestinal tract. Significance: Overexpression of CD24 in colorectal dysplasia provides the opportunity to use an NIR-II fluorescent probe targeting CD24 to detect colorectal neoplasms, including invisible lesions that are missed by white-light colonoscopy., (©2024 American Association for Cancer Research.)

Objectives: This study aims to characterize the bacterial co-occurrence features and potential interactions associated with the presence of sinus tracts in apical periodontitis in a Chinese population by using 16S rRNA next-generation sequencing (NGS)., Methods: Thirty-one samples from twenty-six patients were collected from root canals. Following the extraction of the bacterial DNA, the V3-V4 hypervariable regions of the 16S rRNA gene were sequenced. Compositional diversity, prominent taxa and co-occurrence network analysis were compared according to the presence or absence of sinus tracts., Results: The overall microbiota in two groups exhibited distinguished patterns. Actinomyces dominated in samples with sinus tracts while Prevotella was the most abundant in samples without sinus tracts. The major pathogens in sinus tracts exhibited a complex co-occurrence network, in which Pseudomonas formed a distinctive cluster with enriched abundance, and the extensive correlations centered on Desulfovibrio and Pseudoramibacter may suggest novel dependencies. In the network without sinus tracts, the Bacteroidetes and Firmicutes taxa presented close internal associations., Conclusions: The sequencing results confirmed the complexity of the microbiota in AP. The presence of sinus tracts was associated with distinctive infective patterns and complicated microbial co-infection interaction networks. Further investigations should be adopted to elucidate the relationship between the novel interactions and disease progression., Clinical Significance: Exploring the microbial interactions leads to a better understanding of etiology of apical periodontitis. Utilizing next generation sequencing techniques, our research uncovered the bacterial community structure and observed co-infection networks associated with sinus tracts, providing potential insights for prognosis prediction and targeted therapeutics of persistent inflammation., 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.)

Objectives: This paper aims to construct a system integrating mixed reality technology with artificial algorithm and to evaluate its effectiveness in vascular localization during anterolateral thigh perforator flap surgery to provide new insights for clinical practice., Methods: Twenty patients undergoing anterolateral thigh perforator flap repair were selected. After attaching positioning devices on the lower limb, CT angiography (CTA) scans were performed. The 2D data obtained were converted into a 3D model of the positioning device and vessels. Mixed reality technology was utilized to achieve 3D visualization of perforator vessels. An artificial algorithm was developed in HoloLens 2 to match the positioning device automatically with its 3D model intraoperatively to overlap the perforator vessels with their 3D models. The number of perforator vessels identified within the flap harvesting area and the actual number detected during surgery were recorded to calculate the accuracy rate of vessel identification based on CTA data reconstruction. The distance between the perforator vessel exit points located by the system and the actual exit points was measured, and the error values were calculated. The surgical time required for the system to harvest the anterolateral thigh perforator flap was documented and compared with the surgical time required by conventional methods. The clinical applicability of the system was discussed., Results: The CTA data reconstruction identified 30 perforator vessels, while the actual number found during surgery was 32, resulting in an identification accuracy rate of 93.75%. The average distance between the perforator vessel exit points located by the system and the actual exit points was (1.65±0.52) mm. The average surgical time for flap harvesting with the assistance of the system was (43.45±4.6) min compared with (57.6±7.9) min required by conventional methods. All perforator flaps survived the procedure. One case of flap infection occurred seven days postoperatively, and one case of partial flap necrosis was treated with symptomatic therapy, resulting in delayed healing., Conclusions: The system constructed in this paper can achieve 3D visualization of perforator vessels through mixed reality technology and improve the accuracy of perforator vessel localization using artificial algorithms, hence demonstrating potential application in anterolateral thigh perforator flap harvesting surgeries.

Ischemic stroke is a significant threat to human health. Currently, there is a lack of effective treatments for stroke, and progress in new neuron-centered drug target development is relatively slow. On the other hand, studies have demonstrated that brain microvascular endothelial cells (BMECs) are crucial components of the neurovascular unit and play pivotal roles in ischemic stroke progression. To better understand the complex multifaceted roles of BMECs in the regulation of ischemic stroke pathophysiology and facilitate BMEC-based drug target discovery, we utilized a transcriptomics-informed systems biology modeling approach and constructed a mechanism-based computational multipathway model to systematically investigate BMEC function and its modulatory potential. Extensive multilevel data regarding complex BMEC pathway signal transduction and biomarker expression under various pathophysiological conditions were used for quantitative model calibration and validation, and we generated dynamic BMEC phenotype maps in response to various stroke-related stimuli to identify potential determinants of BMEC fate under stress conditions. Through high-throughput model sensitivity analyses and virtual target perturbations in model-based single cells, our model predicted that targeting succinate could effectively reverse the detrimental cell phenotype of BMECs under oxygen and glucose deprivation/reoxygenation, a condition that mimics stroke pathogenesis, and we experimentally validated the utility of this new target in terms of regulating inflammatory factor production, free radical generation and tight junction protection in vitro and in vivo. Our work is the first that complementarily couples transcriptomic analysis with mechanistic systems-level pathway modeling in the study of BMEC function and endothelium-based therapeutic targets in ischemic stroke., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024. Published by Elsevier B.V.)

Consensus holds that most cells in the embryo are genetically identical and have healthy genomes. However, embryonic cells with abnormal chromosomes are surprisingly frequent. In a recent publication, de Jaime-Soguero et al. report that extracellular developmental signaling pathways, including BMP, FGF, and WNT, can promote or prevent chromosome instability in certain cell types., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Exposure to major life stressors and aberrant functional connectivity have been linked to anxiety and depression, especially in adolescence. However, it remains unclear if specific characteristics of major life stressors and functional network disruptions differentially predict anxiety and depression symptoms over time and, if so, whether they act independently or jointly. We collected baseline lifetime stressor exposure data and resting-state functional magnetic resonance imaging data in a longitudinal sample of 107 adolescents enriched for anxiety and depressive disorders. We examined five stressor characteristics: physical danger, interpersonal loss, humiliation, entrapment, and role change/disruption. Anxiety and depression symptoms were assessed at baseline, 6-month and 12-month follow-ups. Linear mixed effect models tested if these stressor characteristics, functional connectivity within and between frontoparietal, default, and ventral attention networks, and their interactions differentially predicted anxiety and depression symptoms at 6-month and 12-month follow-ups. Greater lifetime severity of physical danger and humiliation prospectively predicted increased anxiety symptoms at both follow-ups, whereas greater lifetime entrapment severity prospectively predicted higher anxiety and depression symptoms. Only the effects of lifetime entrapment severity were robust to including within- and between-network functional connectivity metrics and other significantly predictive stressor characteristics. Lifetime entrapment severity more strongly predicted anxiety symptoms in youth with higher default network connectivity. Greater functional connectivity between frontoparietal and default networks prospectively predicted increased depression symptoms. Taken together, these results underscore the critical importance of using stressor characteristics and functional connectivity jointly to study predictors for adolescent anxiety and depression.

The dual challenges of additive safety and environmental sustainability in the current cosmetics market have attracted significant attention. In this study, we obtained raw materials from natural Chinese medicine, combined with electrospinning technology, developed a new type of environmentally friendly dry nanofiber multifunctional mask with Bletilla striata polysaccharide (BSP) as the material and loaded with the sodium ferulate (SF). The optimal manufacturing process was screened by scanning electron microscopy (SEM), and the diameters of the dry nanofiber facial mask (DNFM) were mainly distributed in the range of 180-240 nm. Volunteer experiments and water contact angle assessments showed that the DNFM had good moisture retention and solubility. The experimental findings showcased that the water vapor transmission rate of the PVA/BSP/SF DNFM was 4607.77 ± 74.12 g/m2/day, and the tyrosinase inhibition rate was 52.88 %, over 98 % inhibition rates against Propionibacterium acnes (P. acnes), and a 94.99 ± 0.24 % DPPH free radical scavenging rate. The mouse group treated with the DNFM displayed stronger resistance to UV damage. Cell Counting Kit-8 (CCK8) and Live/Dead staining experiments verified its safety and biocompatibility. The combined application of electrospinning technology and natural Chinese medicine components provides a new strategy for the development of an environmentally friendly and convenient mask product., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Histone deacetylases (HDACs) are validated drug targets for various therapeutic applications. A series of Tetrahydro-β-carboline-based hydroxamate derivatives, designed as HDAC inhibitors (HDACis), were synthesized. Compound 11g exhibited strong inhibitory activity against HDAC1 and the A549 cancer cell line. Additionally, this compound increased the levels of acetylated histone H3 and H4. Notably, 11g effectively arrested A549 cells in the G2/M phase and also increased ROS production and DNA damage, thereby inducing apoptosis. Further molecular docking experiments illustrated the potential interactions between compound 11g and HDAC1. These findings suggested that the novel Tetrahydro-β-carboline-based HDACis could serve as a promising framework for further optimization as anticancer agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Osteoporosis is a systemic bone metabolism disorder characterized by decreased bone mass and strength. Osteoclasts (OCs) are giant multinucleated cells that regulate bone homeostasis by degrading bone matrix. Excessive OC differentiation and activity can lead to serious bone metabolic disorders including osteoporosis. Current treatments, including antiresorptive drugs, exert considerable adverse effects, including jaw osteonecrosis. Herbal medicines, such as Ninjinyoeito (NYT), may also offer efficacy, but with fewer adverse effects. In this study, we investigated NYT's effects on osteoclastogenesis., Methods: Tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays were performed to examine NYT's effects on OC differentiation and function. OC-related gene expression at mRNA and protein levels was investigated to confirm NYT's inhibitory action against osteoclastogenesis. We also demonstrated involvement of signaling pathways mediated by IκBα and mitogen-activated protein kinases (MAPK) [extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38] and showed nuclear translocation of nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) and nuclear factor kappa B (NF-κB) p65 during osteoclastogenesis., Results: TRAP staining and bone resorption assays confirmed that NYT significantly inhibited OC differentiation and function. Western blot and RT-PCR results showed that NYT ameliorated osteoclastogenesis by suppressing mRNA and protein level expression of OC-related genes. Moreover, blots and immunocytochemistry (ICC) data clarified that NYT abrogates signaling pathways mediated by IκBα and MAPK (ERK, JNK, p38), and demonstrated nuclear translocation of NFATc1 and NF-κB p65 during OC differentiation., Conclusions: These findings suggest NYT is an alternative therapeutic candidate for treating osteoporosis., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Bottlenecks of the freeway generated especially by traffic accidents or temporary work zones contribute to significant reductions in system throughput and hinder the efficient traffic operations. It is imperative to take proactive measures to improve traffic state. With the rapid advancements in intelligent transportation, connected and autonomous vehicles (CAVs) have attracted much attention by its speculated capabilities in improving traffic safety and well-organized operational coordination. Therefore, reasonably utilizing the advantages of CAVs is possible to reduce the impact induced by bottlenecks. In this research, we propose a novel algorithm called CAV-Lead to obtain the CAV's regulated speed under mixed CAVs and human-driven vehicles (HVs) environment to improve the overall utilization of the freeway capacity near bottlenecks. Firstly, we illustrate the basic principle of the CAV-Lead algorithm that takes both microscopic and macroscopic traffic characteristics into account. Then, based on the local spatiotemporal traffic state, the CAV-Lead algorithm is proposed to determine each CAV's speed under mixed flow. Furthermore, a real-time simulation control framework considering the random behavior of HVs is presented. Moreover, several simulation evaluations including comparisons with basic scenarios and similar research are conducted under various CAV market penetration rates (MPRs). The results demonstrate that the CAV-Lead could improve the traffic performance, especially for the high traffic demand with certain MPRs., 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.)

Objective: Utilizing two-sample Mendelian randomization (TSMR) analysis, this study aims to explore the potential bidirectional causal relationship between common nonsteroidal anti-inflammatory drugs (paracetamol, ibuprofen, aspirin) and major depression (MD) from a genetic standpoint., Methods: We employed summarized data from a Genome-Wide Association Study (GWAS) of European populations. The inverse variance weighted (IVW) method was used for TSMR analysis; outcomes were evaluated based on p -value, OR (Odds Ratio), and 95% confidence interval (95% CI)., Results: From a genetic perspective, the study found that the use of paracetamol and ibuprofen increased the risk of MD (IVW (MRE): OR = 2.314, 95% CI: 1.609-3.327; p  = 6.07E-06) and (IVW (MRE): OR = 2.308, 95% CI: 1.780-3.653; p  = 0.002), respectively. No significant causal relationship was found between aspirin and MD ( p  > 0.05). Reverse TSMR analysis found that MD increased the genetic predisposition to use paracetamol, ibuprofen, and aspirin (IVW (MRE): OR = 1.042, 95% CI: 1.030-1.054, p  = 3.07E-12), (IVW (FE): OR = 1.015, 95% CI: 1.007-1.023, p  = 1.13E-04), (IVW (MRE): OR = 1.019, 95% CI: 1.009-1.030, p  = 4.22E-04), respectively. Other analytical methods and sensitivity analyses further supported the robustness and reliability of these findings., Conclusion: This study provides preliminary genetic evidence through bidirectional TSMR analysis that MD increases the genetic predisposition to use paracetamol, ibuprofen, and aspirin, aiding clinicians in devising preventive strategies against the misuse of non-steroidal anti-inflammatory drugs. Moreover, we found that the use of paracetamol and ibuprofen increases the risk of MD, whereas aspirin did not. This suggests a crucial clinical implication: clinicians treating MD patients could opt for the relatively safer aspirin over paracetamol and ibuprofen., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Combining LiDAR points and images for robust semantic segmentation has shown great potential. However, the heterogeneity between the two modalities (e.g. the density, the field of view) poses challenges in establishing a bijective mapping between each point and pixel. This modality alignment problem introduces new challenges in network design and data processing for cross-modal methods. Specifically, 1) points that are projected outside the image planes; 2) the complexity of maintaining geometric consistency limits the deployment of many data augmentation techniques. To address these challenges, we propose a cross-modal knowledge imputation and transition approach. First, we introduce a bidirectional feature fusion strategy that imputes missing image features and performs cross-modal fusion simultaneously. This allows us to generate reliable predictions even when images are missing. Second, we propose a Uni-to-Multi modal Knowledge Distillation (U2MKD) framework, leveraging the transfer of informative features from a single-modality teacher to a cross-modality student. This overcomes the issues of augmentation misalignment and enables us to train the student effectively. Extensive experiments on the nuScenes, Waymo, and SemanticKITTI datasets demonstrate the effectiveness of our approach. Notably, our method achieves an 8.3 mIoU gain over the LiDAR-only baseline on the nuScenes validation set and achieves state-of-the-art performance on the three datasets.

Objective: Sox2 plays crucial roles in tissues homeostasis and regeneration. However, there are lack of a comprehensive examination of Sox2 expression and its functional role in submandibular gland regeneration. Therefore, we aimed to elucidate the impact of Sox2 on submandibular gland regeneration., Materials and Methods: A Sprague-Dawley rat submandibular gland duct ligation/de-ligation regeneration model was conducted in this study. Sox2-shRNA vectors were retro-ductally administered into the submandibular gland to establish a stable Sox2 knockdown model. Conventional histopathological and molecular biological methods were used to investigate phenotypic changes., Results: The submandibular gland normalized completely 28 days after ligature removal (following 7 days of duct ligation). AQP5 expression gradually increased after ligation removal until returning to normal levels. In submandibular gland regeneration, Sox2 re-expressed and co-expressed with AQP5 + acinar cells, and Sox2 expression peaked on day 14, recovered to normal on day 28, reproducing the developmental pattern. Sox2 knockdown hindered gland regeneration and induced irreversible fibrosis. The AQP5 expression was significantly lower than the contemporaneous solely ligated group, while the blue collagen deposition and the Vimentin expression increased prominently. The expression of CD68, IL-1β, TNF-α and IL-17A increased significantly, and epithelial cells in the Sox2 knockdown group expressed higher levels of IL-17A., Conclusions: These findings highlight Sox2 as a crucial regulator of the acinar cell lineage. Sox2 + progenitor cells are pivotal for acinar cell maintenance, which is indispensable for submandibular gland regeneration. Collectively, our findings may help develop targeted interventions for enhancing tissue repair and preventing irreversible fibrosis in salivary gland disorders., Competing Interests: Declaration of Competing Interest There is no conflict of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: This study aimed to improve the stability and utilization of sulforaphene (SFE) and to enhance the intestinal stability and pH-sensitive release of SFE in the gastrointestinal tract. To achieve this objective, calcium chloride (CaCl 2 ) was used as a crosslinking agent to fabricate novel SFE-loaded gellan gum (GG)-ε-polylysine (ε-PL) pH-sensitive hydrogel microspheres by using the ionic crosslinking technique., Results: The molecular docking results of GG, ε-PL, and SFE were good and occurred in the natural state. The loading efficiency (LE) of all samples was above 70%. According to the structural characterization results, GG and ε-PL successfully embedded SFE in a three-dimensional network structure through electrostatic interaction. The swelling characteristics and in vitro release results revealed that the microspheres were pH-sensitive, and SFE was mainly retained inside the hydrogel microsphere in the stomach, and subsequently released in the intestine. The result of cytotoxicity assay showed that the hydrogel microspheres were non-toxic and had an inhibitory effect on human colon cancer Caco-2 cells., Conclusion: Thus, the hydrogel microspheres could improve SFE stability and utilization and achieve the intestinal targeted delivery of SFE. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Luobuma tea is made from the leaves of Apocynum hendersonii (Bt) and A. venetum (Ht) and has been used for a very long time in China and Japan as herbal tea. This study isolated water-soluble polysaccharides from the two species` teas. Physicochemical properties, structural properties, in vitro and in vivo antioxidant and immunomodulatory activities were determined for the first time. The results showed that the Bt and Ht polysaccharides with molecular weights of 31.21 and 49.11 kDa, respectively, composed of arabinose, galactose, rhamnose, glucose, xylose, fucose, and mannose. A dose-dependent nitric oxide production and interleukin-6 inhibitory effects were obtained. Also, they suppressed the expression of cyclooxygenase-2, tumor necrosis factor-α and interleukin-6 mRNA in LPS-induced RAW 264.7 macrophages. Likewise, Bt and Ht have significantly reduced edema in the paws of mice after carrageenan injection. These results suggested that the Luobuma teas polysaccharides can be explored as potential antioxidants and anti-inflammatory agents., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aims to investigate the efficacy and safety of hyperbaric oxygen therapy (HBOT) in the treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation., Methods: This retrospective analysis included 16 patients with late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation between 2016 and 2022. Among them, 8 patients received HBOT in addition to conventional treatment, while the other 8 received only conventional treatment. The clinical efficacy and safety of HBOT were evaluated by comparing the Numeric Rating Scale pain scores and clinical grades of hematuria before and after treatment, reflecting the patients' urinary pain and hematuria status., Results: The patients were divided into two groups based on whether they received HBOT. The group that received HBOT ( n  = 8) had a shorter duration of illness compared to the non-HBOT group ( n  = 8) ( p  < 0.05). The time for the NRS to decrease to below 2 was also shorter in the HBOT group. Furthermore, the patients who received HBOT did not experience any significant adverse reactions., Conclusion: The combination of conventional treatment and hyperbaric oxygen therapy (HBOT) has been shown to improve symptoms such as urinary pain, frequency, urgency, and hematuria in patients with late-onset hemorrhagic cystitis after transplantation. This approach has been proven to be safe and effective.

Objectives: To evaluate the efficacy of low-flow oxygen inhalation in mitigating transient severe motion (TSM) artifacts associated with gadoxetate disodium-enhanced hepatic magnetic resonance imaging (MRI)., Methods: Patients undergoing gadoxetate disodium-enhanced MRI were included. During the examination, the experimental group received oxygen at 2 L/min via nasal cannula, while the control group did not. Images and TSM scores were evaluated and compared across precontrast, arterial, venous, and hepatobiliary phases. Subgroup analyses were conducted based on the presence of pleural effusion or ascites., Results: A total of 325 patients were included. The motion scores were highest in the arterial phase and lowest in the hepatobiliary phase in both groups, but were significantly lower in the experimental group (p < 0.05). The incidence of TSM was significantly lower in the experimental group (3.29%) compared to the control group (13.29%, p = 0.01). While pleural effusion was associated with reduced image quality in both groups (p < 0.05), the image quality in the pleural effusion category was higher in the experimental group than in the control group. Oxygen inhalation showed limited efficacy in mitigating TSM related to ascites., Conclusions: Low-flow oxygen inhalation can effectively reduce the occurrence of gadoxetate disodium-related TSM. Pleural effusion may impair respiratory function and contribute to TSM, which can be alleviated by oxygen supplementation. However, Oxygen inhalation is less effective under the condition of ascites., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In order to guide the formulation of post-stroke treatment strategy in time, it is necessary to have real-time feedback on collateral circulation and revascularization. Currently used near-infrared II (NIR-II) probes have inherent binding with endogenous albumin, resulting in significant background signals and uncontrollable pharmacokinetics. Therefore, the albumin-escaping properties of the new probe, IR-808AC, was designed, which achieved timely excretion and low background signal, enabling the short-term repeatable injection for visualization of cerebral vessels and perfusion. We further achieved continuous observation of changes in collateral vessels and perfusion during the 7-d period in middle cerebral artery occlusion mice using IR-808AC in vivo. Furthermore, using IR-808AC, we confirmed that remote ischemic conditioning could promote collateral vessels and perfusion. Finally, we evaluated the revascularization after thrombolysis on time in embolic stroke mice using IR-808AC. Overall, our study introduces a novel methodology for safe, non-invasive, and repeatable assessment of collateral circulation and revascularization in real-time that is crucial for the optimization of treatment 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 Ltd. All rights reserved.)

As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions (Δ15-26 and Δ136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.

Background: LncRNAs play diverse roles and participate in various biological processes within the human body. It has been frequently reported that they are involved in the occurrence and development of recurrent spontaneous miscarriage. PRNCR1 , a crucial player in several types of cancers, may also have implications for recurrent spontaneous miscarriage risk. However, the correlation between PRNCR1 rs13252298 A > G polymorphism and this risk remains unclear. In summary, we conducted the following experiments to investigate the association between the PRNCR1 polymorphic site rs13252298 and susceptibility to recurrent spontaneous miscarriage., Method: Our research included 695 healthy controls and 413 patients with recurrent spontaneous miscarriage from southern China. Genotyping was performed using the TaqMan method., Result: Our findings revealed that there is a relationship between PRNCR1 rs13252298 A > G polymorphism and lower susceptibility to recurrent spontaneous miscarriage (AG and AA: adjusted OR = 0.794, 95% CI = 0.527-1.196, p  = 0.2696; GG and AA: adjusted OR = 0.705, 95% CI = 0.542-0.917, p  = 0.0092; dominant model: adjusted OR = 0.722, 95% CI = 0.563-0.926, p  = 0.0104; recessive model: adjusted OR = 0.949, 95% CI = 0.644-1.398, p  = 0.7912)., Conclusion: The results of our study demonstrate that the PRNCR1 rs13252298 A > G allele may contribute to a decreased risk of recurrent spontaneous miscarriage. The rs13252298 polymorphism could potentially serve as a biomarker for detecting recurrent spontaneous miscarriage risk and aiding prevention efforts., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: To explore the role of oxidative stress on glycogen synthase kinase-3 in lymphocytes of diabetes mellitus (DM) patients complicated with cerebral infarction (CI)., Materials and Methods: A total of 186 DM patients were enrolled according to the inclusion criteria and exclusion criteria, including 89 DM patients alone (DM group) and 97 DM patients with CI (DM + CI) group. Eighty-one patients with CI were selected as the CI group, and 80 normal subjects over 50 years were selected as the control group. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, and malondialdehyde (MDA) content in serum were determined by colorimetric assays. Phosphorylation of GSK-3β was measured by enzyme-linked immunosorbent assay., Results: (1) Compared with the control group, the SOD and GSH-Px activities in the DM group and DM + CI group were decreased, accompanied by higher MDA content. Furthermore, phosphorylation of GSK-3β was decreased. (2) In the DM + CI group, SOD activity was decreased on days 7 and 10 and month 3 compared to the CI group and was decreased on day 7 compared to the DM group. MDA content was increased from day 0 to month 3 compared to the CI group. On days 1, 7, and 10, GSH-Px activity was lower than the DM group, and on day 10 and month 3, it was lower than the CI group. Phosphorylation of GSK-3β was decreased on days 7 and 10 compared to the DM group and was decreased from day 1 to month 3 compared to the CI group., Conclusion: In the present study, we demonstrated that the oxidative stress in peripheral lymphocytes of DM patients complicated with CI was stronger, and the GSK-3 activity was higher. It suggested that oxidative stress might enhance the GSK-3 activity, which might provide a diagnostic and therapeutic approach for DM complicated with CI, and targeting GSK-3 is a promising therapeutic target for the treatment of type 2 diabetes and its complications., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Background: Blood-brain barrier (BBB) disruption after stroke is closely associated with brain tissue edema and neuronal injury, which requires accurate assessment. However, there is a lack of appropriate BBB imaging modality in vivo. As albumin in the blood could cross the damaged BBB into brain tissue after stroke, it serves as a biomarker for BBB disruption. Therefore, we aimed to develop an albumin-seeking near-infrared (NIR) probe to assess BBB disruption in stroke., Results: We proposed a chemoselective strategy for seeking albumin with NIR dyes and identified an optimal probe to evaluate BBB disruption in stroke. The probe combined a NIR fluorescent dye with inherent albumin-targeting moieties and exhibited high affinity and selectivity for binding to albumin. Using a mouse stroke model, the probe displayed a high-resolution visualization of the location and extent of BBB disruption in vivo and correlated well with BBB leakage measured by Evans blue ex vivo. A dual-channel NIR-II imaging was successfully used to simultaneously assess BBB disruption and cerebral perfusion after stroke. Furthermore, we applied this method to dynamically evaluate the BBB disruption process and reperfusion of thrombolytic therapy in a stroke model in real time, which showed excellent application value., Conclusions: We developed an albumin-seeking NIR probe that accurately evaluated BBB disruption in a safe, non-invasive and real-time manner in various stroke models, and has a great potential guiding stroke treatment in a real-time manner., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Animal Ethical Committee of The First Hospital of Jilin University (20210642) and conforms to all the relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Acute kidney injury (AKI) is a clinically complex syndrome with a high incidence and mortality rate in the intensive care unit (ICU). Early identification of high-risk patients and timely intervention are crucial., Objective: A local database was used to construct a model that predicts the incidence of AKI in ICU patients within 48 hours., Materials and Methods: We conducted a study involving 9,628 critically ill patients at Zhejiang Provincial People's Hospital and divided the cohort into derivation and validation groups. We collected and analyzed demographic data, vital signs, laboratory tests, medications, clinical interventions, and other information for all patients, resulting in a total of 232 variables. Six different machine learning algorithms were employed to construct models, and the optimal model was selected and validated., Results: A total of 2,441 patients were included, of whom 1,138 (46.62%) met the AKI criteria. A model was derived that included 16 variables such as albumin transfusion, fluid balance, diastolic blood pressure (DBP), partial pressure of oxygen (PO 2 ), blood glucose (GLU), platelet (PLT), baseline serum creatinine (bSCr), serum sodium, age, epinephrine, proton pump inhibitor (PPI), intra-abdominal infection, anemia, diabetes, glycerin fructose, and nutritional pathway. The area under the receiver operating characteristic curve (AUC) was 0.822. Subgroup analysis revealed the impact of blood pressure fluctuations on AKI. Additionally, the study demonstrated a bidirectional effect of albumin and fluid balance on AKI., Conclusion: This model is highly accurate and may facilitate the early diagnosis of and interventions for AKI.

Dynamic therapy response is strongly associated with cancer outcomes. This study aimed to evaluate the significance of longitudinal Epstein-Barr virus (EBV) DNA and radiological tumor regression in risk stratification and response-adaptive treatment in locally-advanced nasopharyngeal carcinoma (LA-NPC). In total, 1312 patients from two centers were assigned to the training and validation cohorts. Based on the multipoint examination of EBV-DNA and tumor response, four post-induction chemotherapy, four mid-radiotherapy, and four post-radiotherapy subgroups were established. Then seven phenotypes were further generated according to different permutations and combinations. These phenotypes were subsequently congregated into four response clusters, which reflect distinct biological treatment responses. The four response clusters correlated with an evident 5-year progression-free survival in both the training and external validation cohorts (5-year: training cohort 91.1 %, 82.8 %, 30.6 %, and 10.0 %; external validation 94.4 %, 55.6 %, 40.0 %, and 12.7 %) had superior prognostic performance compared to TNM staging and nomogram model (concordance index: training cohort-0.825 vs. 0.603 vs. 0.756 and external validation-0.834 vs. 0.606 vs. 0.789). Importantly, the response clusters exhibited an excellent capability in selecting candidates who can benefit from adjuvant chemotherapy. In conclusion, risk stratification based on the dynamic assessment of both radiological and biological responses can significantly enhance prognostic insights and shed light on individualized treatment modifications in LA-NPCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A novel porous amorphous-crystalline heterostructured CoNiP nanowire arrays ((a-c)CoNiP/CC) is presented. TEM observations and compositional calculations revealed ≈14.5% of the amorphous regions (a-CoNiP) are interleaved in the crystalline regions (c-(Co 3.6 Ni 0.4 )P 4 ), forming massive amorphous-crystalline heterogenous interfaces composed of the same elements. Only 38 and 64 mV overpotentials for the (a-c)CoNiP/CC catalyst are required to reach the current density of -10 mA cm 2 in acid and alkaline electrolyte, respectively, which is very close to the overpotentials (35 and 55 mV) of the commercial Pt/C HER catalyst. The theoretical calculation revealed that the (a-c)CoNiP/CC has a completely different enhancement mechanism of HER reaction in acid-base electrolytes. In particular, due to the natural corrosion resistance of the amorphous interface, the HER performance of this catalyst under the high current density condition is much better than that of the Pt/C catalyst either in acidic or in alkaline, suggesting its prospect for commercial applications., (© 2024 Wiley‐VCH GmbH.)

With the growing need for precise campus electricity management, understanding load patterns is crucial for improving energy efficiency and optimizing energy use. However, detailed electricity load data for campus buildings and their internal equipment is often lacking, hindering research. This paper introduces an energy consumption monitoring dataset from The Hong Kong University of Science and Technology (HKUST) campus in Hong Kong, comprising data from over 1400 meters across more than 20 buildings and collected over two and a half years. Using the Brick Schema curation strategy, raw data was curated into a research-ready format. This dataset supports various research tasks, including load pattern recognition, fault detection, demand response strategies, and load forecasting., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Understanding the core competencies of English for Specific Purposes (ESP) students is vital for designing ESP curricula and refining methodologies. This study sought to comprehensively assess the core competencies of Business English students in Chinese higher vocational colleges (HVCs). A questionnaire survey was conducted among 394 Business English students from five HVCs. The survey evaluated core competencies across gender and academic grades using a model comprisinging four primary dimensions and twelve sub-modules. The results revealed significant disparities in core competency development among Business English students, particularly across gender and academic grades within the specified competence indicator dimensions. These findings highlight the need to enhance in the core competencies of these students, indicating current deficienciess in their development. The identified disparities and areas for improvement in core competencies provide valuable insights for educators and institutions to customize teaching methodologies and improve curriculum design, better addressing the needs of Business English students in HVCs., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The increasing demand for correcting ptosis has made mastopexy one of the most common procedures in plastic surgery. While various techniques have been developed, clinical outcomes often require refinement. In this study, we employed an inferolaterally pedicled, tongue-shaped parenchymal flap to perform auto-augmentation mastopexy via periareolar approach., Methods: Periareolar double-ring incisions were designed, de-epithelialization was performed between the inner and outer circles. Following subcutaneous separation of the breast parenchyma, an inferolaterally based, tongue-shaped parenchymal flap was elevated and rotated to fill posterior space of the breast, raising the nipple-areola complex (NAC). The parenchyma on both sides of the incision was sutured together to reduce the breast base and enhance central breast projection. The breast measurements and BREAST-Q scores were used to assess clinical outcomes and patients' satisfaction. Patients were also asked to rate their nipple sensation., Results: A total of 34 female patients were retrospectively analyzed after being treated with our modified auto-augmentation mastopexy technique from January 2016 to June 2023. All patients healed without postoperative complications such as poor wound healing, hematoma, infection, or nipple necrosis. Four patients reported decreased nipple sensation postoperatively. Breast measurements revealed improved projection, nipple elevation, and significant reductions in both mammary base width and areola diameter. BREAST-Q scores indicated significant improvements in postoperative breast satisfaction and quality of life., Conclusions: Our modified periareolar auto-augmentation mastopexy provides a viable solution for patients with mild to severe breast ptosis, excluding cases with insufficient breast volume, seeking breast ptosis correction without synthetic materials or implants. This technique delivers natural, aesthetically pleasing results, significantly enhancing both patient appearance and quality of life., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest to disclose. Ethical Approval: The study was approved by the Ethics Committee of the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University and was conducted in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed Consent: Informed consent was obtained from all subjects involved in the study. Written informed consent was also obtained from the patients to publish this paper., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)