Search

We performed a prospective matched case-control study, with six-month follow-up for discharged subjects, to evaluate the direct clinical and financial impact of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) infections in Singaporean hospitals. Consecutive nosocomial MRSA-infected cases at both tertiary public sector hospitals in Singapore were matched for age, specialty service, major surgical procedure (if applicable) and Charlson comorbidity index with up to two non-infected controls each. Chart reviews and subject interviews were performed during hospitalisation and also upon six months post-discharge for survivors. The outcomes analysed were: mortality, length of hospitalisation (LOS), healthcare-associated financial costs, and health-related quality of life. The last was evaluated via an interviewer-administered EuroQol-5D questionnaire on discharge, with conversion to a single health state summary index. Attributable outcomes were ascertained by conditional logistic and linear regression. There were 181 cases and 351 controls. MRSA infection was independently associated with in-hospital death [14.4% vs 1.4%; odds ratio (OR): 5.54; 95% confidence interval (CI): 1.63-18.79, P=0.006], longer LOS (median of 32 days vs 7 days; coefficient: 1.21; 95% CI: 1.02-1.40, P<0.001), higher hospitalisation costs (median of US$18,129.89 vs US$4,490.47; coefficient: 1.14; 95% CI: 0.93-1.35; P<0.001), higher post-discharge healthcare-associated financial costs (median of US$337.24 vs US$259.29; coefficient: 0.39; 95% CI: 0.06-0.72; P=0.021), and poorer health-related quality of life (coefficient: -0.14; 95% CI: -0.21 to -0.08; P<0.001). Outcomes were not significantly different between both hospitals. The attributable individual, institutional and societal impact of MRSA infections is considerable in Singapore. Preventing such infections will result in substantial improvements in patient outcomes and healthcare delivery. [ABSTRACT FROM AUTHOR]

Burns patients are highly susceptible to infection, and preventing and treating infection are integral to the successful management of severe burns.Multi-resistant Acinetobacter baumannii (MR-AB) strains are becoming increasingly important in nosocomial infections. We conducted a retrospective study of all adult admissions to the Singapore General Hospital (SGH) National Burns Center over an 18-month period. The only independent risk factors for the acquisition of MR-AB were the APACHE II score on admission and the number of intravascular lines placed. The only independent predictor of infection with MR-AB was the number of intravascular lines placed. The only independent predictors of longer length of stay were the total number of operations required and infection with MR-AB. The only independent predictor of mortality was the APACHE II score. This is in contrast to other studies that have suggested that the acquisition of MR-AB is an independent risk factor for mortality. [ABSTRACT FROM AUTHOR]

Background: Appropriate weight gain reduces the risk of fetal macrosomia and large for gestational age (LGA) in women with gestational diabetes mellitus (GDM), especially in the second and third trimester. This study aims to identify the optimal weight g-ain for such women across several pre-pregnancy body mass index (BMI) categories to lower the risk of macrosomia and LGA., Methods: This retrospective cohort study enrolled women with GDM in north Taiwan who delivered between January 2012 and July 2022. BMI cut-offs were based on Chinese-specific guidelines and used to classify the participants as underweight (<18.5 kg/m 2 ), normal weight (18.5-24.0 kg/m 2 ), overweight (24.0-28.0 kg/m 2 ), or obese (>28 kg/m 2 ). Receiver operator curve analysis was used to determine the optimum GWG cut-off ranges to predict macrosomia / LGA, and uni- and multivariate analyses were used to analyze risk factors. In addition, a multivariable model predicting macrosomia and LGA in infants was developed., Results: A total of 963 participants was included in our analysis. Optimal mean weekly rates of GWG in the second and third trimesters were 0.43 kg/week and 0.61 kg/week, respectively, in the underweight and normal weight group, and 0.33 kg/week and 0.32 kg/week, respectively, in the overweight and obesity group., Conclusion: The 2009 IOM guidelines, offering weight gain recommendations for pregnant women, appear to be applicable to Asian women diagnosed with GDM. This indicates that it is essential for such women to maintain an adequate total GWG throughout pregnancy. Physicians should address GWG using the IOM guidelines and trigger intervention when it is required to reduce macrosomia and LGA occurrence., Competing Interests: Declaration of competing interest All authors are without conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject of their manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

Our comprehensive understanding of the multi-species ACE2 adaptiveness of sarbecoviruses remains elusive, particularly for those with various receptor binding motif (RBM) insertions/deletions (indels). Here, we analyzed RBM sequences from 268 sarbecoviruses categorized into four RBM indel types. We examined the ability of 20 representative sarbecovirus Spike glycoproteins (S) and derivatives in utilizing ACE2 from various bats and several other mammalian species. We reveal that sarbecoviruses with long RBMs (type-I) can achieve broad ACE2 tropism, whereas viruses with single deletions in Region 1 (type-II) or Region 2 (type-III) exhibit narrower ACE2 tropism. Sarbecoviruses with double region deletions (type-IV) completely lost ACE2 usage, which is restricted by clade-specific residues within and outside RBM. Lastly, we propose the evolution of sarbecovirus RBM indels and illustrate how loop lengths, disulfide, and residue determinants shape multi-species ACE2 adaptiveness. This study provides profound insights into the mechanisms governing ACE2 usage and spillover risks of sarbecoviruses., (© 2024. The Author(s).)

Objective: The purpose of this experiment is to explore the role of long intergenic noncoding RNA 261 (LINC00261) gene in the chemoresistance and clinical prognosis of epithelial ovarian cancer (EOC)., Methods: We used matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry to detect the methylation levels of the LINC00261 promoter region in EOC patient specimens. The expression levels of LINC00261, miR-545-3p, and MT1M in EOC patients were evaluated by quantitative real-time reverse transcriptase PCR (RT-qPCR). Spearman's correlation analysis was used for relevance analyses and clinical prognosis was counted by Kaplan-Meier analysis. Stable overexpressed LINC00261 SKOV3 cells were established to test the influence of LINC00261 on proliferation, platinum sensitivity, migration, and invasion., Results: The promoter region methylation level of the LINC00261 was hypermethylated and LINC00261 was significantly downregulated in platinum-resistant EOC tissues. The methylation level of LINC00261was significantly negative correlated with its RNA expression in EOC. Moreover, hypermethylation and lower expression of LINC00261 in EOC patients were related to shorter progression-free survival (PFS) and overall survival (OS). Furthermore, Spearman's correlation analysis showed that the expression of miR-545-3p had a negative relevance with LINC00261. According to the website prediction, MT1M might be the downstream target gene of LINC00261. Expression of MT1M was negatively correlated with miR-545-3p and positively with LINC00261 in EOC tissues. And lower MT1M mRNA expression was correlated with chemotherapy resistance and worse prognosis. In vitro, overexpression of LINC00261 could inhibit cisplatin resistance, proliferation, and suppression of migration and invasion in SKOV3 cells., Conclusions: This research indicates that the aberrant hypermethylation and low expression of LINC00261 were associated with platinum resistance and adverse outcomes in EOC patients., (© 2024 Japan Society of Obstetrics and Gynecology.)

Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent., (© 2024. The Author(s).)

Plants such as herbs, vegetables, fruits, and cereals are closely related to human life. Developing effective testing methods to ensure their safety and quantify their active components are of significant importance. Recently, nanomaterials with enzyme-like activity (known as nanozymes) have been widely developed in various assays, including colorimetric, fluorescence, chemiluminescence, and electrochemical analysis. This review presents the latest advances in analyzing phytochemicals and hazardous substances in plant samples based on nanozymes, including some active ingredients, organophosphorus pesticides, heavy metal ions, and mycotoxins. Additionally, the current shortcomings and challenges of the actual sample analysis were discussed., (© 2024. The Author(s).)

Patients with schizophrenia often lack physical activity, which, together with physical complications, can lower their expected lifespan. Exercise strengthens their physical and mental health. The primary aim of this study was to examine the effectiveness of a walking exercise intervention in improving physical fitness, body mass index, waist-to-hip ratio, and depressive symptoms in patients with schizophrenia. A quasi-experimental study design was used. Seventy-six participants were recruited from the psychiatric daycare center at a hospital in Northern Taiwan. They were divided into two groups. The intervention group received a walking exercise intervention, while the control completed their daily courses at the psychiatric daycare center. The changes in both groups' physical fitness, BMI, waist-to-hip ratio, and depressive symptoms were monitored. Cardiorespiratory endurance significantly improved in the intervention group, attesting to the effectiveness of the walking exercise intervention. Their depression level significantly decreased across all measurement stages. The group walking exercise reduced sedentary behaviors and increased the participants' autonomous motivation, hip circumference, and cardiorespiratory fitness. Structured exercise programs may increase the patients' hippocampal neuroplasticity and reduce their depressive symptoms. The walking exercise intervention positively affected physiological traits, physical fitness, and mental health of the participants., 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.

Selective separation of 137 Cs is significant for the sustainable development of nuclear energy and environmental protection, due to its strong radioactivity and long half-life. However, selective capture of 137 Cs + from radioactive liquid waste is challenging due to strong coulomb interactions between the adsorbents and high-valency metal ions. Herein, we propose a strategy to resolve this issue and achieve specific Cs + ion recognition and separation by modulating the stacking modes of layered perovskites. We demonstrate that among niobate-based perovskites, ALaNb 2 O 7 (A = Cs, H, K, and Li), HLaNb 2 O 7 shows an outstanding selectivity for Cs + even in the presence of a large amount of competing M n+ ions (M n+  = K + , Ca 2+ , Mg 2+ , Sr 2+ , Eu 3+ , and Zr 4+ ) owing to its suitable void fraction and space shape, brought by the stacking mode of layers. The Cs + capture mechanism is directly elucidated at molecular level by single-crystal structural analyses and density functional theory calculations. This work not only provides key insights in the design and property optimization of perovskite-type materials for radiocesium separation, but also paves the way for the development of efficient inorganic materials for radionuclides remediation., (© 2024. The Author(s).)

Novel microbial strains capable of efficient degradation of TNT and typical intermediates (2-ADNT and 4-ADNT) in aerobic/anaerobic environment were screened and isolated from ammunition-contaminated sites. The key genomes, transcriptomes, proteins, and metabolic factors for microbial detoxification/tolerance to pollutants in anaerobic and aerobic environments were analyzed for the first time. The bacterial genome, which is rich in metabolism and environmental information-processing functional genes, provides transcriptional and translational-related proteins for detoxifying/tolerating pollutants. At the transcriptional level, bacteria significantly expressed genes related to inositol phosphate metabolism for regulating membrane transport, maintaining the cytoskeleton, and signal transduction. At the protein level, genes involved in antioxidation, fat metabolism, sugar synthesis/degradation, and pyruvate metabolism were significantly expressed. At the metabolic level, riboflavin metabolism, which regulates membrane integrity, protects against oxidative stress, and maintains the sugar-protein-fat balance, showed significant responses. Bacteria simultaneously regulate amino acid metabolism, carbohydrate metabolism, and N/P/S cycles to maintain homeostatic cellular energy supplies. The key pathway for pollutant degradation in bacteria is nitrotoluene degradation. The molecular mechanism of bacterial tolerance to pollutants involves the regulation of oxidative phosphorylation and basic cycle pathways to maintain gene transcription, protein translation, and metabolic cycles., 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.)

Two-photon polymerization (TPP) as an unparalleled technology empowers the rapid prototyping of customized three-dimensional (3D) micro/nanostructures, garnering noticeable interest in tissue engineering, drug delivery, and regenerative medicine. These applications have a high requirement on the biocompatibility and integrity of 3D structures. Therefore, it is important to develop two-photon initiator with good water-solubility, initiation efficiency, and biocompatibility. Here, we share our insights into the development of a water-soluble two-photon initiator (WTPI) and applications from the material and manufacturing perspective. We highlight the nonlinear optical properties and the synthesis of WTPI through three pathways. Then we further demonstrate the applications of the TPP technique in the aqueous phase in the fields of tissue engineering, 4D printing, and ceramic manufacturing. Finally, a general conclusion and outlook are provided for the future development and application of WTPI.

Purpose: Microglia-like cells derived from stem cells (iMG) provide a plentiful cell source for studying the functions of microglia in both normal and pathological conditions. Our goal is to establish a simplified and effective method for generating iMG in a precisely defined system. Additionally, we aim to achieve functional maturation of iMG through coculture with retinal organoids., Methods: In this study, iMG were produced under precisely defined conditions. They were subjected to LPS and poly IC stimulation. Additionally, we examined distinct phenotypic and functional variances between iMG and HMC3, a commonly used human microglia cell line. To investigate how the retinal cell interaction enhances microglial properties, iMG were cocultured with retinal organoids, producing CC-iMG. We performed RNA sequencing, electrophysiological analysis, and transmission electron microscope (TEM) to examine the maturation of CC-iMG compared to iMG., Results: Our results demonstrated that iMG performed immune-responsive profiles closely resembling those of primary human microglia. Compared to HMC3, iMG expressed a higher level of typical microglial markers and exhibited enhanced phagocytic activity. The transcriptomic analysis uncovered notable alterations in the ion channel profile of CC-iMG compared to iMG. Electrophysiological examination demonstrated a heightened intensity of inward- and outward-rectifying K+ currents in CC-iMG. Furthermore, CC-iMG displayed elevated numbers of lysosomes and mitochondria, coupled with increased phagocytic activity., Conclusions: These findings contribute to advancing our understanding of human microglial biology, specifically in characterizing and elucidating the functions of CC-iMG, thereby offering an in vitro microglial model for future scientific research and potential clinical applications in cell therapy.

Healthcare systems must embody equity, diversity, and inclusion (EDI) and, in the event of unfairness, appropriate policies / countermeasures should be enacted. The healthcare system response to the COVID-19 pandemic not only highlighted how socioeconomic disparities affect mortality risk but also posed significant challenges to the successful practice of EDI in healthcare. In light of this, this article was written to provide an overview of EDI, analyze the international efforts to promote it, and suggest strategies for promoting EDI in infectious disease healthcare using COVID-19 as an example. In healthcare settings, equity centers on ensuring patients receive fair treatment regardless of race, gender, age, or socioeconomic status; diversity centers on healthcare providers understanding the uniqueness of patients from different cultural backgrounds and the health barriers they face; and inclusion centers on ensuring patients are treated with respect and given the attention they deserve. During pandemics, social determinants of health (SDOH) greatly impact patient health outcomes and hinder the practice of EDI. Reflecting on the impact of COVID-19, healthcare systems can actively apply EDI in clinical practice to provide to all patients equitable access to healthcare opportunities and outcomes. Practical strategies include establishing EDI committees within healthcare systems, monitoring relevant data, conducting staff training, and continuously addressing the SDOH and needs of marginalized groups to achieve EDI in healthcare.

Competing Interests: Th authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Global pollution has exacerbated accumulation of toxicants like methylmercury (MeHg) in seafood. Human exposure to MeHg has been associated with long-term neurodevelopmental delays and impaired cardiovascular health, while many micronutrients in seafood are beneficial to health. The largest MeHg exposure source for many general populations originates from marine fish that are harvested from the global ocean and sold in the commercial seafood market. Here, we use high-resolution catch data for global fisheries and an empirically constrained spatial model for seafood MeHg to examine the spatial origins and magnitudes of MeHg extracted from the ocean. Results suggest that tropical and subtropical fisheries account for >70% of the MeHg extracted from the ocean because they are the major fishing grounds for large pelagic fishes and the natural biogeochemistry in this region facilitates seawater MeHg production. Compounding this issue, micronutrients (selenium and omega-3 fatty acids) are lowest in seafood harvested from warm, low-latitude regions and may be further depleted by future ocean warming. Our results imply that extensive harvests of large pelagic species by industrial fisheries, particularly in the tropics, drive global public health concerns related to MeHg exposure. We estimate that 84 to 99% of subsistence fishing entities globally likely exceed MeHg exposure thresholds based on typical rates of subsistence fish consumption. Results highlight the need for both stringent controls on global pollution and better accounting for human nutrition in fishing choices., Competing Interests: Competing interests statement:The authors declare no competing interest.

There has long existed a substantial disparity in access to radiotherapy globally. This issue has only been exacerbated as the growing disparity of cancer incidence between high-income countries (HIC) and low and middle-income countries (LMICs) widens, with a pronounced increase in cancer cases in LMICs. Even within HICs, iniquities within local communities may lead to a lack of access to care. Due to these trends, it is imperative to find solutions to narrow global disparities. This requires the engagement of a diverse cohort of stakeholders, including working professionals, non-governmental organizations, nonprofits, professional societies, academic and training institutions, and industry. This review brings together a diverse group of experts to highlight critical areas that could help reduce the current global disparities in radiation oncology. Advancements in technology and treatment, such as artificial intelligence, brachytherapy, hypofractionation, and digital networks, in combination with implementation science and novel funding mechanisms, offer means for increasing access to care and education globally. Common themes across sections reveal how utilizing these new innovations and strengthening collaborative efforts among stakeholders can help improve access to care globally while setting the framework for the next generation of innovations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans, demonstrating a intriguing "elixir in youth, poison in elder" phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57, a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans, and C46G7.1, unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1/nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca 2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch-clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety-like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3-d subacute restraint stress (SRS), a well-validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS-induced anxiety-related behaviors, whereas hM3Dq-mediated chemogenetic or SRS-induced activation of vHPC astrocytes enhances anxiety-like behaviors, which are reversed by intra-vHPC application of the ionotropic glutamate N-methyl-d-aspartate receptor antagonists. Furthermore, intra-vHPC or systemic application of the N-methyl-d-aspartate receptor antagonist memantine, a U.S. FDA-approved drug for Alzheimer's disease, fully rescues SRS-induced anxiety-like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety-related disorders., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population., (© 2024 John Wiley & Sons Ltd.)

Cottonseed meal (CSM) and cottonseed protein concentrate (CPC) serve as protein alternatives to fish meal and soybean meal in the feed industry. However, the presence of gossypol residue in CSM and CPC can potentially trigger severe intestinal inflammation, thereby restricting the widespread utilization of these two protein sources. Probiotics are widely used to prevent or alleviate intestinal inflammation, but their efficacy in protecting fish against gossypol-induced enteritis remains uncertain. Here, the protective effect of Pediococcus pentosaceus, a strain isolated from the gut of Nile tilapia (Oreochromis niloticus), was evaluated. Three diets, control diet (CON), gossypol diet (GOS) and GOS supplemented with P. pentosaceus YC diet (GP), were used to feed Nile tilapia for 10 weeks. After the feeding trial, P. pentosaceus YC reduced the activity of myeloperoxidase (MPO) in the proximal intestine (PI) and distal intestine (DI). Following a 7-day exposure to Aeromonas hydrophila, the addition of P. pentosaceus YC was found to increase the survival rate of the fish. P. pentosaceus YC significantly inhibited the oxidative stress caused by gossypol, which was evidenced by lower reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in PI and DI. Addition of P. pentosaceus YC significantly inhibited enteritis, with the lower expression of pro-inflammatory cytokines (il-1β, il-6, il-8) and higher expression of anti-inflammatory cytokines tgf-β. RNA-seq analysis indicated that P. pentosaceus YC supplementation significantly inhibited nlrc3 and promoted nf-κb expression in PI and DI, and the siRNA interference experiment in vivo demonstrated that intestinal inflammation was mediated by NLRC3/NF-κB/IL-1β signaling pathway. Fecal bacteria transplantation experiment demonstrated that gut microbiota mediated the protective effect of P. pentosaceus YC. These findings offer valuable insights into the application of P. pentosaceus YC for alleviating gossypol-induced intestinal inflammation in fish., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Vocal fold leukoplakia (VFL) is a precancerous lesion of laryngeal cancer, and its endoscopic diagnosis poses challenges. We aim to develop an artificial intelligence (AI) model using white light imaging (WLI) and narrow-band imaging (NBI) to distinguish benign from malignant VFL., Methods: A total of 7057 images from 426 patients were used for model development and internal validation. Additionally, 1617 images from two other hospitals were used for model external validation. Modeling learning based on WLI and NBI modalities was conducted using deep learning combined with a multi-instance learning approach (MIL). Furthermore, 50 prospectively collected videos were used to evaluate real-time model performance. A human-machine comparison involving 100 patients and 12 laryngologists assessed the real-world effectiveness of the model., Results: The model achieved the highest area under the receiver operating characteristic curve (AUC) values of 0.868 and 0.884 in the internal and external validation sets, respectively. AUC in the video validation set was 0.825 (95% CI: 0.704-0.946). In the human-machine comparison, AI significantly improved AUC and accuracy for all laryngologists (p < 0.05). With the assistance of AI, the diagnostic abilities and consistency of all laryngologists improved., Conclusions: Our multicenter study developed an effective AI model using MIL and fusion of WLI and NBI images for VFL diagnosis, particularly aiding junior laryngologists. However, further optimization and validation are necessary to fully assess its potential impact in clinical settings., Level of Evidence: 3 Laryngoscope, 134:4321-4328, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To compare and explore the characteristics of squamous cell carcinoma (SCC), adenocarcinoma (AC) and adenosquamous carcinoma (ASC), usual-type endocervical adenocarcinoma (UEA) and gastric adenocarcinoma (GAC) of cervix., Materials and Methods: A total of 728 cervical cancers (254 cases of AC, 252 cases of ASC, and 222 cases of SCC) confirmed by histopathology were retrospectively reviewed. Among AC, 119 UEA and 47 GAC were included. Clinical baseline data and tumor morphological features on MRI (including tumor location, shape, diameter and volume, margin, growth pattern, presence of fluid component or cyst, heterogenous and peritumoral enhancement) of all cases were collected and analyzed. The signal intensity (SI) of tumor and gluteus maximus muscle were measured and their ratios (SIR) were calculated based on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and contrast-enhanced T1WI at arterial and delay phases (A/DCE-T1WI). These clinical and MRI features were compared between SCC, AC and ASC, UEA and GAC, and the specific ones of each subtype were identified., Results: There was a significant difference in SCC-Ag, CA-199, CEA, ADC value, SIR-DWI, presence of intratumor cyst and peritumoral enhancement between AC and ASC; in patient age, menopausal status, International Federation of Gynecology and Obstetrics (FIGO) stage, SCC-Ag, CA-125, CA-199, CEA, tumor shape, growth pattern, margin, presence of intratumor fluid component and cyst, tumor diameter and volume, ADC value, SIR-T1WI, SIR-T2WI, and SIR-DWI between SCC and AC, as well as SCC and ASC. Also, there was a significant difference in deep stromal invasion (DSI), peritumoral and heterogenous enhancement between SCC and AC, and in SIR-ACE-T1WI between SCC and ASC. There was a significant difference in reproductive history, menopausal status, FIGO stage, CA-199, DSI, lymph node metastasis (LNM), parametrial invasion (PMI), tumor location, shape, margin, growth pattern, presence of fluid component and cyst, tumor diameter and volume, SIR-T1WI, SIR-DWI, and heterogenous enhancement between GAC and UEA., Conclusion: The clinical and MRI features with significant differences among SCC, AC and ASC, and between UEA and GAC, can help to identify each subtype of cervical cancer., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis., Methods: A total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups' progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared., Results: The surgical staging group started radiotherapy 10.2 days (range 9-12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively)., Conclusion: Performing surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs., (© 2024. The Author(s).)

Objectives. It has been established that an adult's perceived ability to effectively address negative emotions predicts their life satisfaction. To increase the understanding of ethnic minority children's mental health and quality of life, this study examined the relationship between perceived emotional self-efficacy and life satisfaction of Hispanic children. Methods. Using the nonexperimental-correlational research design and the convenience sampling method, a total of 176 fourth-, fifth-, and sixth-grade students (73 boys, 103 girls; 88% Hispanic) in one public elementary school on the US-Mexico border were recruited to participate in this study. Emotional self-efficacy was measured using the emotional subscale of the Self-Efficacy Questionnaire for Children and subjective well-being was measured using the Student Life Satisfaction Scale. Spearman correlation and ordinal regression analyses were used to test the study hypotheses. Results. Consistent with findings from the current literature, emotional self-efficacy was positively associated with subjective well-being. Children in lower elementary grades were more likely to report higher emotional self-efficacy than those in higher elementary grades. Boys were more likely to report higher life satisfaction than girls. Conclusions and Relevance. Using a sample of elementary school children with Hispanic backgrounds on the US-Mexico border, this study attested to the empirical link between emotional self-efficacy and life satisfaction. Our study findings stress the importance of early identification of students with low emotional self-efficacious beliefs and the early introduction of social-emotional learning programs in elementary schools to enhance students' emotional self-efficacy. This study contributes to positive psychology literature and provides insights for future school-based mental health practice and research., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Competing Interests: DR is a member of the Board of Directors and receives travel support from the Union for International Cancer Control; declares grant funding from the Canadian Cancer Society and the Leukemia and Lymphoma Society; and declares consulting fees and stock options from Need. MLY is funded by a National Health and Medical Research Council Investigator Grant (APP 2018108).

Background: Cognitive impairment (CI) is common in Parkinson's disease (PD). Multiple brain regions and their interactions are involved in PD associated CI. Magnetic resonance imaging (MRI) technology is a non-invasive method in investigating brain structure and inter-regional connections. In this study, by comparing cortical thickness, subcortical volume, and brain network topology properties in PD patients with and without CI, we aimed to understand the changes of brain structure and structural covariance network properties in PD associated CI., Methods: A total of 18 PD patients with CI and 33 PD patients without CI were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, Mini Mental State Examination Scale, Non-motor Symptom Rating Scale, Hamilton Anxiety Scale, and Hamilton Depression Scale were assessed. All participants underwent structural 3T MRI. Cortical thickness, subcortical volume, global and nodal network topology properties were measured., Results: Compared with PD patients without CI, the volumes of white matter, thalamus and hippocampus were lower in PD patients with CI. And decreased whole-brain local efficiency is associated with CI in PD patients. While the cortical thickness and nodal network topology properties were comparable between PD patients with and without CI., Conclusion: Our findings support the alterations of brain structure and disruption of structural covariance network are involved in PD associated CI, providing a new insight into the association between graph properties and PD associated CI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Lin, Ma, Huang, Yuan, Zhu, Sheng, Zou, Zhu, Zhang and Wang.)

Background: Chronic inflammation is closely linked to Chronic Obstructive Pulmonary Disease (COPD); however, the impact of the Dietaryq Inflammatory Index (DII) on mortality among COPD patients remains uncertain., Objective: To assess the correlation between the DII and all-cause mortality in COPD patients using data from the National Health and Nutrition Examination Survey (NHANES)., Methods: We conducted a retrospective cohort study on 1,820 COPD patients from the NHANES dataset (1999-2018). The influence of DII on mortality was evaluated using multivariate Cox regression, smoothing spline fitting, and threshold effect analysis. Additionally, Kaplan-Meier survival analysis was performed to compare survival curves among different DII groups. Subgroup analyses and E-values identified sensitive cohorts and assessed unmeasured confounding., Results: Over an average follow-up of 91 months, multivariate Cox regression models revealed a significant positive correlation between DII scores and mortality risk, with each unit increase in DII associated with a 10% higher risk of death (HR: 1.10, 95% CI: 1.03-1.16; P = 0.002). Among the DII tertiles, individuals in the second tertile (T2: 1.23-2.94) experienced a 67% increase in mortality risk compared to those in the lowest tertile (T1: -5.28-1.23) (HR: 1.67, 95% CI: 1.26-2.21; p < 0.001). The third tertile (T3) did not show a statistically significant increase in mortality risk (HR: 1.30, 95% CI: 0.98-1.72; p =0.074). A restricted cubic spline analysis indicated a significant nonlinear association between DII and all-cause mortality ( p = 0.021). Threshold effect analysis further revealed that below a DII of 2.19, there was a significant increase in all-cause mortality risk (HR = 1.19, 95% CI: 1.07-1.33; p = 0.002), while at or above this threshold, the risk increase was not statistically significant (HR=0.89, 95% CI: 0.68-1.15; p = 0.380). Kaplan-Meier analysis revealed significant differences in survival curves among DII tertiles ( p < 0.001), with the lowest DII tertile showing the highest survival probability. Both subgroup and sensitivity analyses confirmed the robustness of these findings., Conclusion: DII is positively correlated with mortality risk in COPD patients, showing nonlinear characteristics and threshold effects, underscoring its prognostic value., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Zhi, Xie, Jiang and Qu.)

This study aims to explore the impact of Multimedia-Assisted Teaching (MAT) on the quality of physical education (PE) instruction in universities, with a particular focus on badminton courses. A quasi-experimental design was employed, including pre-tests and post-tests, involving two badminton classes at Ming Chuan University, with a total of 101 students. These two classes were assigned to an experimental group (using MAT) and a control group (traditional teaching methods). The research instrument used was the Physical Education Teaching Quality Scale (PETQ), which includes four factors: course content, teaching strategies, classroom management, and learning assessment. The results indicated that, compared to traditional teaching methods, the use of MAT significantly enhanced students' perception of the quality of PE instruction. The experimental group scored significantly higher than the control group across all scale factors, suggesting that MAT is more effective in capturing students' attention and improving learning outcomes. The conclusion suggests that MAT has significant advantages in improving the quality of physical education instruction. The integration of MAT enables more flexible lesson planning and enhances the learning process through the features of multimedia-assisted teaching. It is recommended that physical education teachers consider applying multimedia technologies to aid teaching, in order to increase student engagement and effectiveness.

Out-of-plane polarization is a highly desired property of two-dimensional (2D) ferroelectrics for application in vertical sandwich-type photoferroelectric devices, especially in ultrathin ferroelectronic devices. Nevertheless, despite great advances that have been made in recent years, out-of-plane polarization remains unrealized in the 2D hybrid double perovskite ferroelectric family. Here, from our previous work 2D hybrid double perovskite HQERN ((S3HQ) 4 EuRb(NO 3 ) 8 , S3HQ=S-3-hydroxylquinuclidinium), we designed a molecular strategy of F-substitution on organic component to successfully obtain FQERN ((S3FQ) 4 EuRb(NO 3 ) 8 , S3FQ=S-3-fluoroquinuclidinium) showing circularly polarized luminescence (CPL) response. Remarkably, compared to the monopolar axis ferroelectric HQERN, FQERN not only shows multiferroicity with the coexistence of multipolar axis ferroelectricity and ferroelasticity but also realizes out-of-plane ferroelectric polarization and a dramatic enhancement of Curie temperature of 94 K. This is mainly due to the introduction of F-substituted organic cations, which leads to a change in orientation and a reduction in crystal lattice void occupancy. Our study demonstrates that F-substitution is an efficient strategy to realize and optimize ferroelectric functional characteristics, giving more possibility of 2D ferroelectric materials for applications in micro-nano optoelectronic devices., (© 2024 Wiley-VCH GmbH.)

Background and Aim: The characteristics of autoimmune liver diseases (AILDs), including primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and PBC-AIH overlap syndrome (OS), have rarely been investigated and compared in Asia., Methods: At the Taiwan tertiary referral center, 330 PBC patients (87% treated with ursodeoxycholic acid [UDCA]), 143 AIH patients (94.4% treated with immunosuppressive therapy [IST]) and 21 PBC-AIH OS patients (85.7% treated with UDCA and IST) were enrolled., Results: Compared with AIH patients, PBC patients were older at baseline and had greater female-to-male sex ratios, alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) levels, and liver cirrhosis (LC), dyslipidemia, and hepatic and cardiometabolic complication rates. PBC patients had the lowest transaminase levels, whereas AIH patients had the highest transaminase levels. PBC patients had greater 22-year all-cause mortality and liver transplantation (ACMaLT) (43.5 vs 25.4%, P = 0.004), LC (75 vs 58.5%, P < 0.01), dyslipidemia (54.4 vs 45.9%, P = 0.001), and cerebrovascular accident (11.3 vs 0.8%, P = 0.019) cumulative incidences (CIs) than did AIH patients; PBC-AIH OS patients had greater systemic lupus erythematosus (28.9 vs 8.9%, P = 0.009) CI than did PBC patients. Baseline ALP (hazard ratio: 1.001), albumin (0.514), platelet count (0.997), and LC (3.438) were associated with ACMaLT; age (1.110), albumin (0.350), cirrhosis (46.219), and hepatitis C virus antibody positivity (5.068) were associated with hepatocellular carcinoma (HCC); and female sex (2.183) and body mass index (1.054) were associated with autoimmune diseases., Conclusions: Compared with AIH patients, PBC patients had greater cardiometabolic CI, and ACMaLT CI, which was associated with cholestasis, liver functional reserve and LC. Older AILD patients with LC and females with obesity demand special caution for the development of HCC and extrahepatic autoimmune diseases, respectively., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Herein, we present a novel and efficient method for the synthesis of two new polycyclic aromatic hydrocarbons, 1 and 2 , through the electrocyclization-dehydrogenation of diradicaloids. The proposed oxidative electrocyclization via intermediate diradicaloids is monitored by electron paramagnetic resonance and ultraviolet-visible spectroscopy. Interestingly, 1 exhibits chirality because of its inherent helical skeleton, and 2 features long-wavelength absorption and near-infrared emission properties due to its extended π-conjugation.

We established a zebrafish model of depression-like behaviour induced by exposure to artificial light at night (ALAN) and found that nobiletin (NOB) alleviated depression-like behaviour. Subsequently, based on the results of a 24-h free movement assay, clock gene expression and brain tissue transcriptome sequencing, the glycolysis signalling pathway was identified as a potential target through which NOB exerted antidepressant effects. Using the ALAN zebrafish model, we found that supplementation with exogenous L-lactic acid alleviated depressive-like behaviour. Molecular docking and molecular dynamics simulations revealed an inter-molecular interaction between NOB and the pyruvate kinase isozyme M1/M2 (PKM2) protein. We then used compound 3 k to construct a zebrafish model in which PKM2 was inhibited. Our analysis of this model suggested that NOB alleviated depression-like behaviour via inhibition of PKM2. In summary, NOB alleviated depressive-like behaviour induced by ALAN in zebrafish via targeting of PKM2 and activation of the glycolytic signalling pathway., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. This work has not been submitted/published or being submitted to another journal., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Vaccine-induced T cells and neutralizing antibodies are essential for protection against SARS-CoV-2. Previously, we demonstrated that an antigen delivery system, pullulan nanogel (PNG), delivers vaccine antigen to lymph node medullary macrophages and thereby enhances the induction of specific CD8 + T cells. In this study, we revealed that medullary macrophage-selective delivery by PNG depends on its binding to a C-type lectin SIGN-R1. In a K18-hACE2 mouse model of SARS-CoV-2 infection, vaccination with a PNG-encapsulated receptor-binding domain of spike protein decreased the viral load and prolonged the survival in the CD8 + T cell- and B cell-dependent manners. T cell receptor repertoire analysis revealed that although the vaccine induced T cells at various frequencies, low-frequency specific T cells mainly promoted virus clearance. Thus, the induction of specific CD8 + T cells that respond quickly to viral infection, even at low frequencies, is important for vaccine efficacy and can be achieved by SIGN-R1 + medullary macrophage-targeted antigen delivery., (© 2024. The Author(s).)