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Abstract The study was aimed to investigate the positive impact of bicarbonate Ringer’s solution on postoperative outcomes in patients who underwent laparoscopic right hemihepatectomy. Patients in the two groups were infused with lactated Ringer’s solution (LRS, n = 38) and the bicarbonate Ringer’s solution (BRS, n = 38) at a rate of 5 ml·kg–1·h–1. The stroke volume was monitored and 200 ml of hydroxyethyl starch with 130/0.4 sodium chloride injection (Hes) of a bolus was given in the first 5–10 min. The main outcome was to test lactic acid (LAC) concentration before and after surgery. The concentrations of LAC in the LRS group were higher than in the BRS group at 2 h after operation began, at the end of the operation and 2 h after the operation. Overall, the parameters including pH, base excess (BE), HCO3 −, aspartate transaminase (AST) and alanine transaminase (ALT) were improved. The values of bilirubin in the LRS group were higher and albumin were lower than in the BRS group at post-operation 1st and 2nd day (P

Abstract Background Research on the fatty acid metabolism related gene SLC27A2 is currently mainly focused on solid tumors, and its mechanism of action in hematological tumors has not been reported. Method This study aims to explore the pathological and immune mechanisms of the fatty acid metabolism related gene SLC27A2 in hematological tumors and verify its functional role in hematological tumors through cell experiments to improve treatment decisions and clinical outcomes of hematological tumors. Result This study identified the fatty acid metabolism related gene SLC27A2 as a common differentially expressed gene between DLBCL and AML. Immune microenvironment analysis showed that SLC27A2 was significantly positively correlated with T cell CD4 + , T cell CD8 + , endothelial cells, macrophages, and NK cells in DLBCL. In AML, there is a significant negative correlation between SLC27A2 and B cells, T cell CD8 + , and macrophages. SLC27A2 participates in the immune process of hematological tumors through T cell CD8 + and macrophages. The GESA results indicate that high expression of SLC27A2 is mainly involved in the fatty acid pathway, immune pathway, and cell cycle pathway of DLBCL. The low expression of SLC27A2 is mainly involved in the immune pathway of AML. Therefore, SLC27A2 is mainly involved in the pathological mechanisms of hematological tumors through immune pathways, and cell experiments have also confirmed that SLC27A2 is involved in the regulation of DLBCL cells. Conclusion In summary, our research results comprehensively report for the first time the mechanism of action of SLC27A2 in the immune microenvironment of DLBCL and AML, and for the first time verify the cycle and apoptotic effects of the fatty acid related gene SLC27A2 in DLBCL cells through cell experiments. Research can help improve the treatment of AML and DLBCL patients.

Abstract Background THOC7-AS1 and FSTL1 expression are frequently upregulated in cutaneous squamous cell carcinoma (cSCC). However, their molecular biological mechanisms remain elusive and their potential as therapeutic targets needs urgent exploration. Methods Human tissue samples were used to evaluate clinical parameters. In vitro and in vivo experiments assessed biological functions. Quantitative PCR, western blot, immunohistochemistry, immunocytochemistry, immunoprecipitation, RNA fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation, silver staining, chromatin immunoprecipitation, dual luciferase reporter assays etc. were utilized to explore the molecular biological mechanisms. Results We found FSTL1 is an oncogene in cSCC, with high expression in tumor tissues and cells. Its elevated expression closely associates with tumor size and local tissue infiltration. In vitro and in vivo, high FSTL1 expression promotes cSCC proliferation, migration and invasion, facilitating malignant behaviors. Mechanistically, FSTL1 interacts with ZEB1 to promote epithelial-to-mesenchymal transition (EMT) in cSCC cells. Exploring upstream regulation, we found THOC7-AS1 can interact with OCT1, which binds the FSTL1 promoter region and promotes FSTL1 expression, facilitating cSCC progression. Finally, treating tumors with THOC7-AS1 antisense oligonucleotides inhibited cSCC proliferative and migratory abilities, delaying tumor progression. Conclusions The THOC7-AS1/OCT1/FSTL1 axis regulates EMT and promotes tumor progression in cSCC. This study provides clues and ideas for cSCC targeted therapy.

Abstract Background It is well established that traumatic brain injury (TBI) causes acute and chronic alterations in systemic immune function and that systemic immune changes contribute to posttraumatic neuroinflammation and neurodegeneration. However, how TBI affects bone marrow (BM) hematopoietic stem/progenitor cells chronically and to what extent such changes may negatively impact innate immunity and neurological function has not been examined. Methods To further understand the role of BM cell derivatives on TBI outcome, we generated BM chimeric mice by transplanting BM from chronically injured or sham (i.e., 90 days post-surgery) congenic donor mice into otherwise healthy, age-matched, irradiated CD45.2 C57BL/6 (WT) hosts. Immune changes were evaluated by flow cytometry, multiplex ELISA, and NanoString technology. Moderate-to-severe TBI was induced by controlled cortical impact injury and neurological function was measured using a battery of behavioral tests. Results TBI induced chronic alterations in the transcriptome of BM lineage−c-Kit+Sca1+ (LSK+) cells in C57BL/6 mice, including modified epigenetic and senescence pathways. After 8 weeks of reconstitution, peripheral myeloid cells from TBI→WT mice showed significantly higher oxidative stress levels and reduced phagocytic activity. At eight months after reconstitution, TBI→WT chimeric mice were leukopenic, with continued alterations in phagocytosis and oxidative stress responses, as well as persistent neurological deficits. Gene expression analysis revealed BM-driven changes in neuroinflammation and neuropathology after 8 weeks and 8 months of reconstitution, respectively. Chimeric mice subjected to TBI at 8 weeks and 8 months post-reconstitution showed that longer reconstitution periods (i.e., time post-injury) were associated with increased microgliosis and leukocyte infiltration. Pre-treatment with a senolytic agent, ABT-263, significantly improved behavioral performance of aged C57BL/6 mice at baseline, although it did not attenuate neuroinflammation in the acutely injured brain. Conclusions TBI causes chronic activation and progressive dysfunction of the BM stem/progenitor cell pool, which drives long-term deficits in hematopoiesis, innate immunity, and neurological function, as well as altered sensitivity to subsequent brain injury.

Abstract Background Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), has been associated with several cancer risks in observational studies, but the observed associations have been inconsistent and may face the bias of confounding and reverse causality. The potential causal relationships between IBD and the risk of cancers remain largely unclear. Methods We performed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analyses using summary genome-wide association study (GWAS) data across East Asian and European populations to evaluate the causal relationships between IBD and cancers. Sensitivity analyses for the MR approach were additionally performed to explore the stability of the results. Results There were no significant genetic correlations between IBD, CD, or UC and cancers (all P values > 0.05) in East Asian or European populations. According to the main MR analysis, no significant causal relationship was observed between IBD and cancers in the East Asian population. There were significant associations between CD and ovarian cancer (odds ratio [OR] = 0.898, 95% CI = 0.844–0.955) and between UC and nonmelanoma skin cancer (OR = 1.002, 95% CI = 1.000–1.004, P = 0.019) in the European population. The multivariable MR analysis did not find any of the above significant associations. There was no shared causal variant to prove the associations of IBD, CD, or UC with cancers in East Asian or European populations using colocalization analysis. Conclusions We did not provide robust genetic evidence of causal associations between IBD and cancer risk. Exposure to IBD might not independently contribute to the risk of cancers, and the increased risk of cancers observed in observational studies might be attributed to factors accompanying the diagnosis of IBD.

Abstract Objectives Ultrasound-guided superior laryngeal nerve (SLN) block is a practical and painless approach to avoid the hemodynamic stress response during endotracheal intubation and relieve sore throat after laryngeal surgery. The main purpose of this study was to establish an optimal dosage of local anesthetic when performing SLN block to help anesthetists balance analgesia and side effects. Methods Twenty fresh larynx specimens were obtained immediately after resection and then injected with 2-, 3-, 4-, or 5- mL of a lidocaine-blue dye mixture at bilateral SLN puncture sites. Superficial areas of deposited blue dye were measured. Dye leakage and surrounding dyed tissue were recorded. Another 40 patients were included in the ultrasound investigation. Distances between the internal branch of the SLN (iSLN) and adjacent structures were calculated. Results The dye spread area was greater with the administration of larger doses, especially to the visceral space. A 2- or 3-mL injection of local anesthetic was sufficient to infiltrate the SLN gap. A higher incidence of dye leaking out of the thyrohyoid membrane and anterior epiglottis space was observed; furthermore, there was substantially more dyed hyoid/thyroid cartilage with 4 and 5 mL of injected dye mixture than 2 mL. There was no significant difference between the specimen and ultrasound measurements of for length of iSLN-adjacent structures. Conclusions In the Chinese population, 2- or 3- mL of local anesthetic is a safe dose during SLN block. A larger volume could overflow from the cavity to cause complications. The thyrohyoid membrane combined with the superior laryngeal artery is a reliable target for positioning the iSLN during ultrasound-guided regional anesthesia.

Abstract Background Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics. Results To validate the concept, we designed an s-tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for 68Ga or 177Lu radiolabeling and tumor radiotheranostics, a trans-cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [68Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [177Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [68Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [68Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [177Lu]Lu-PSMA-Tz, with the injection of the signal amplification module, approximately five-fold higher tumor uptake of [177Lu]Lu-PSMA-Tz (24.33 ± 2.53% ID/g) was obtained when compared to [177Lu]Lu-PSMA-Tz alone (5.19 ± 0.26%ID/g) at 48 h post-injection. Conclusion In summary, the proposed strategy has the potential to expand the toolbox of pretargeted radiotherapy in the field of theranostics. Graphical Abstract

Abstract Activation of the Hippo pathway by angiomotins to limit colorectal cancer progression is prevalent, whereas the regulation of angiomotins remains elusive. In this study, we uncover the involvement of an upregulated E3 ubiquitin ligase called RNF166, which destabilizes angiomotins, activates YAP, and is associated with a poor prognosis in colorectal cancer patients. Mechanistically, RNF166 specifically recognizes PARsylated angiomotin, a modification mediated by tankyrase at specific amino acid residues (D506, E513, E516, and E528). The tankyrase inhibitor XAV939, effectively prevents RNF166-dependent destabilization of angiomotins and subsequent activation of YAP. Additionally, YAP-5SA, a constitutively active form of YAP, rescues colorectal cancer progression following knockdown of RNF166. Importantly, the C-terminus of RNF66, particularly the Di19-ZF domain, is the crucial region responsible for recognizing ADP-ribosylated angiomotins. Together, this work not only sheds light on the regulation of the Hippo pathway in colorectal cancer but also uncovers a novel poly(ADP-ribose)-binding domain, which may serve as a potential therapeutic target for intervention.

A sensitive and reliable method was developed and validated for the simultaneous determination of 6 carbamate pesticides and relevant metabolites based on the modified fast QuEChERS (quick, easy, cheap, effective, rugged and safe) method combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method was also applied in the analysis of 23 commonly consumed oilseeds and oil samples. The sample was extracted with acetonitrile for three times and then the extracted solution was filtered directly through 250 mg precipitated silica adsorbent (PSA) and 250 mg C18. The mobile phase was water (containing 0.1% formic acid) and acetonitrile. The external standard protocols were adopted to validate the method in terms of recovery, linearity, precision, sensitivity, and relative standard deviation (RSD) under the optimized conditions. The linear calibration curves with different ranges were established with R2 > 0.997 3, limit of detections (LODs) ranged from 0.100 µg/kg to 2.000 µg/kg and limit of quantitations (LOQs) ranged from 0.300 µg/kg to 6.000 µg/kg. The limit of detection meets the detection requirement for the maximum residue limits in practical samples. Meanwhile, the recoveries ranged from 60.2% to 116.6% with associated RSDs ranged from 0.33% to 5.35% in 10 oilseeds matrices and ranged from 61.9% to 116.9% with RSDs ranged from 0.30% to 5.02% in 13 oil matrices. These features do make the UPLC-MS/MS an ideal analytical platform for accurate and high throughput analysis of carbamates residues in the complex matrix.

Malaria remains a major public health concern. The rapid spread of resistance to antimalarial drugs is a major challenge for malaria eradication. Timely and accurate molecular monitoring based on practical detection methods is a critical step toward malaria control and elimination. In this study, two rapid detection techniques, allele-specific PCR (AS‒PCR) and recombinase-aided amplification (RAA) combined with CRISPR/Cas12a, were established, optimized and assessed to detect single nucleotide polymorphisms in the Plasmodium falciparum exonuclease (Pfexo) gene related to suspected piperaquine resistance. Moreover, phosphorothioate and artificial mismatches were introduced into the allele-specific primers for AS‒PCR, and crRNA-mismatched bases were introduced into the RAA‒CRISPR/Cas12a assay because crRNAs designed according to conventional rules fail to discriminate genotypes. As a result, the detection limits of the AS‒PCR and RAA‒CRISPR/Cas12a assays were 104 copies/μL and 103 copies/μL, respectively. The detection threshold for dried blood spots was 100‒150 parasites/μL, with no cross-reactivity against other genotypes. The average cost of AS‒PCR is approximately $1 per test and takes 2–3 h, whereas that of the RAA‒CRISPR/Cas12a system is approximately $7 per test and takes 1 h or less. Therefore, we provide more options for testing single nucleotide polymorphisms in the Pfexo gene, considering economic conditions and the availability of instruments, equipment, and reagents, which can contribute to the molecular monitoring of antimalarial resistance.

Summary: Generation of CRISPR-Cas9-edited cortical neurons from human pluripotent stem cells (hPSCs) enables the study of gene functions and neural disease mechanisms. Here, we present a protocol for developing iCas9-iNgn2 hPSC, an inducible cell line that allows the simultaneous induction of the neuralizing transcription factor Ngn2 and the Cas9 nuclease to rapidly generate edited human cortical neurons. We describe the steps of the protocol from transducing iCas9-iNgn2 with guide RNA-containing lentivirus to producing edited cortical neurons in about 2 weeks.For complete details on the use and execution of this protocol, please refer to Dhaliwal et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Alkali-activated materials (AAM) are considered a type of green cementitious material because they are produced without the grinding and calcining required for cement production, significantly reducing carbon emissions. However, their production typically involves the use of commercial alkalis, which are often corrosive, irritating, and expensive. As an industrial waste from sodium carbonate production, soda residue (SR) has a large reserve and is challenging to dewater and utilize, making its disposal a widespread technical challenge. In this paper, considering the alkaline nature and high salt content of SR, a soda residue activated granulated blast-furnace slag cementitious material (SAG) was synthesized directly using undried and unground SR slurry as the alkali activator, with a mass ratio of SR to granulated blast-furnace slag (GBFS) of 30:70. The effects of ambient temperature (AT) curing, water curing, various heat curing temperatures (45°C, 60°C, 75°C, and 90°C), and different heat curing durations (6 h, 12 h, 18 h, and 24 h) on the properties of SAG were investigated. Specifically, the effect of curing conditions on the mechanical properties of SAG was analyzed through unconfined compressive strength (UCS) testing of mortar specimens. The impact of curing conditions on the phase composition and changes in SAG was characterized using XRD, TG, and FTIR, while the effect on the microstructure of SAG was characterized using SEM. The results showed that SAG achieved the highest UCS (3 d/56 d: 28.1 MPa/36.7 MPa) when subjected to heat curing at 75°C for 12 h. The UCS increased significantly by 3022 % and 321 %, respectively, compared to those under AT sealed curing. This was attributed to the fact that SAG under heat curing produced more C-(A)-S-H gels and hydrocalumite crystals, optimizing pore structure and resulting in a denser microstructure. However, exceeding the threshold temperature of 75°C led to an excessively rapid hydration reaction that adversely affected the further dissolution of GBFS and the uniform distribution of hydration products, thereby diminishing the positive effects of heat curing on UCS. In addition, excessively prolonging the heat curing time exacerbated the development of microcracks within the SAG, leading to a deterioration of UCS over age. In this paper, a novel AAM was synthesized using undried and unground industrial waste without the addition of commercial alkali, and the impact of curing conditions on their properties was studied. This broadens the range of applications for SAG, fills a gap in research on the impact of curing conditions on AAM without commercial alkali, and provides a theoretical basis for the low-carbon utilization of industrial waste.

ABSTRACTThe launch of large language models (LLMs) like ChatGPT in late 2022 and the anticipated arrival of future GPT-x iterations have marked the beginning of the generative artificial intelligence (GAI) era. We conducted a systematic review of how to integrate LLMs including GPT and other GAI models into geospatial science, based on 293 papers obtained from four databases of academic publications – Web of Science (WoS), Scopus, SSRN and arXiv – 26 papers were eventually included for analysis. We statistically outlined the share of domains where LLMs and other GAI models, the type of data that have been used for these models, and the modelling tasks and roles that they play. We also pointed out the challenges and future directions for the next research agenda – along with which we could better position ourselves in the mainstream of science and the cutting-edge research paradigm as others leverage insights from the growing data deluge.

ABSTRACTDigital twin railway is a pivotal foundation for the intelligent construction and maintenance of railway engineering projects within extensive open spaces. Its essence is the integrated representation and association management of multi-granularity spatiotemporal data, executable analysis models, and professional knowledge. These elements are characterized by the prominent characteristics of multi-source, heterogeneity, and massive volume. However, current decentralized and independent management strategies often neglect the dynamic coupling relationships between them, and numerous multi-path joins and conversion aggregation operations exist across various spatial scale applications. Consequently, this results in challenges such as the inability to dynamically couple data-model-knowledge and conduct global association retrieval, thereby limiting the potential for real-time analysis and intelligent application capabilities. To address these problems, we first constructed a tripartite graph model ([Formula: see text]) that explicitly associates temporal, spatial, and interactive relationships. Subsequently, an association management architecture was proposed, accompanied by a global association graph index ([Formula: see text]) and a global-local indexing mechanism. Finally, a prototype system for railway data-model-knowledge association management was developed. The effectiveness of the distributed association management method was demonstrated by employing a case study of high-temperature safety risk analysis in railway tunnel engineering with multi-physics field coupling.

AimsA strategy based on therapeutic drug monitoring and population pharmacokinetic (popPK) models would likely increase the rate of clinical remission (CR) after infliximab (IFX) induction in patients with Crohn’s disease (CD). This study aimed to evaluate the relationship between early IFX levels and antibodies to infliximab (ATI) and CR at week 14 and simulate the probability of attaining the identified exposure target.MethodsPatients with CD (n = 140) treated with IFX were enrolled to develop the popPK model. Of these, 43 moderate-to-severe patients with CD were followed up at week 14. Simulations were performed on patients with different dosage regimens and covariates.ResultsIFX levels >20.08 μg/mL at week 2, >18.44 μg/mL at week 6, and >3.08 μg/mL at week 14 were linked to CR. A one-compartment model fit the data best. The covariates influencing clearance were fat free mass, albumin and ATI levels. To achieve IFX levels >20.08 μg/mL at week 2, ≥400 mg IFX was predicted to be required in over 50% patients with 45–70 kg and 35–45 g/L albumin, except for patients with 70 kg and 30 g/L albumin.ConclusionIFX levels >20.08 μg/mL at week 2 and absence of ATI at week 14 are associated with CR. Optimising IFX induction dosing will be critical to achieve the target of early IFX levels associated with CR.

Abstract Objective This study aims to explore the symptom experiences and psychological feelings of lung cancer patients after radical lobectomy in China. Methods A qualitative study was conducted using face‐to‐face semistructured interviews with lung cancer patients who had a radical lobectomy for treatment of their cancer during the convalescence period. Participants (n = 18) were recruited from a general hospital in China, and patients were selected using purposive sampling from September 2021 to February 2022. Interviews were recorded and transcribed verbatim, and Colaizzi's seven‐step method of phenomenology was used. The Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist was conducted to report the study. Results Four themes were extracted from the interview data: physiological dimensions (fatigue, cough or sputum, chest tightness and shortness of breath, daily activities affected, sleep disturbance, lack of appetite); psychological dimensions (negative emotion, fear of cancer recurrence, learning to accept reality, strengthened faith and hope); family dimensions (heavy economic burden, perceived family care, improved health management behavior); and social dimensions (perceived support of medical staff, decreased sense of social value and self‐identity, changes in social and working style). Conclusion Lung cancer patients are still troubled by many problems during the postoperative recovery period. Medical staff should design and implement effective evaluations and targeted interventions for patients' physical and mental health as soon as possible to improve patients' physical and mental health, as well as their quality of life.

Abstract Medulloblastoma (MB) stands as one of the prevalent malignant brain tumors among pediatric patients. Despite its prevalence, the intricate interplay between the regulatory program driving malignancy in MB cells and their interactions with the microenvironment remains insufficiently understood. Leveraging the capabilities of single‐cell Assay for Transposase‐Accessible Chromatin sequencing (scATAC‐seq), the chromatin accessibility landscape is unveiled across 59,015 distinct MB cells. This expansive dataset encompasses cells belonging to discrete molecular subgroups, namely SHH, WNT, Group3, and Group4. Within these chromatin accessibility profiles, specific regulatory elements tied to individual subgroups are uncovered, shedding light on the distinct activities of transcription factors (TFs) that likely orchestrate the tumorigenesis process. Moreover, it is found that certain neurotransmitter receptors (NTRs) are subgroup‐specific and can predict MB subgroup classification when combined with their associated transcription factors. Notably, targeting essential NTRs within tumors influences both the in vitro sphere‐forming capability and the in vivo tumorigenic capacity of MB cells. These findings collectively provide fresh insights into comprehending the regulatory networks and cellular dynamics within MBs. Furthermore, the significance of the TF‐NTR regulatory circuits is underscored as prospective biomarkers and viable therapeutic targets.

IntroductionCadmium (Cd) is a highly toxic trace element that occurs in large quantities in agricultural soils. The cultivation of industrial crops with high phytoremediation potential, such as kenaf, could effectively reduce soil Cd contamination, but the mechanisms of toxicity, tolerance, and detoxification remain unclear.MethodsIn this study, the effects of different Cd concentrations (0, 100, 250, and 400 µM) on growth, biomass, Cd uptake, physiological parameters, metabolites and gene expression response of kenaf were investigated in a hydroponic experiment.Results and discussionThe results showed that Cd stress significantly altered the ability of kenaf to accumulate and transport Cd; increased the activity of hydrogen peroxide (H2O2), superoxide anion (O2−), and malondialdehyde (MDA); reduced the activities of superoxide dismutase (SOD) and catalase (CAT); and decreased the content of photosynthetic pigments, resulting in significant changes in growth and biomass production. Exposure to Cd was found to have a detrimental effect on the ascorbate–glutathione (AsA–GSH) cycle in the roots, whereas it resulted in an elevation in AsA levels and a reduction in GSH levels in the leaves. The increased content of cell wall polysaccharides under Cd stress could contribute to Cd retention in roots and limited Cd transport to above-ground plant tissues. Metabolomic analyses revealed that alanine, aspartate, and glutamate metabolism, oxidative phosphorylation, ABC transporter, and carbon metabolism were the major metabolic pathways associated with Cd stress tolerance. Cd stress increased gene expression of IRT1 and MTP1 in roots, which resulted in kenaf roots accumulating high Cd concentrations. This study extends our knowledge of the factors regulating the response of kenaf to Cd stress. This work provided a physiological and metabolomic perspective on the mechanism controlling the response of kenaf to Cd stress.

Background: The effect of prognostic nutritional index (PNI) on predicting prognosis of endometrial cancer (EC) patients has been widely analyzed, but no consistent findings are obtained. We therefore performed a meta-analysis for determining accurate role of PNI in predicting EC prognosis. Methods: We comprehensively searched PubMed, Web of Science, Embase, Cochrane Library, and CNKI databases from inception till January 5, 2024. Correlation between PNI and survival outcomes in EC was evaluated by pooled hazard ratios (HRs) and 95 % confidence intervals (CIs). Results: There were altogether eight articles involving 3,164 patients enrolled into this meta-analysis. According to our pooled results, low PNI significantly predicted the dismal overall survival (OS) (HR = 1.72, 95%CI = 1.33–2.22, p

This study investigated the effects of compound probiotics (CP) on AFB1-induced cytotoxicity in Sertoli TM4 cells. The L9 (3 × 3) orthogonal test was conducted to determine the optimal CP required for high AFB1 degradation in the artificial gastrointestinal fluid in vitro. The maximal AFB1 degradation rate was 40.55 % (P < 0.05) when the final viable count was 1.0 × 105 CFU/mL for Bacillus subtilis, Lactobacillus casein, and Saccharomyces cerevisiae. The effects of CP and the CP supernatant (CPS) on TM4 cell viability were evaluated to achieve the optimal protective conditions. When CPS4 (corresponding to CP viable counts of 1.0 × 104 CFU/mL) was added to the TM4 cells for 24 h, the cell viability reached 108.86 % (P < 0.05). AFB1 reduced TM4 cell viability in a concentration- and time-dependent manner at an AFB1 concentration ranging from 0 to 1.5 μM after 48-h AFB1 exposure. The optimal AFB1 concentration/times for low- and high damage models were 0.5 and 1.25 μM both for 24 h, which decreased viability to 76.04 % and 65.35 %, respectively. however, CPS4 added to low- and high-damage models increased the cell viability to 97.43 % and 75.12 %, respectively (P < 0.05). Transcriptome sequencing was performed based on the following designed groups: the control, 0.5 μM AFB1, 1.25 μM AFB1, CPS4, and CPS4+0.5 μM AFB1. The Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was further performed to identify significantly enriched signaling pathways, which were subsequently verified. It was shown that AFB1 induced apoptosis by blocking the PI3K-AKT-mTOR pathway and upregulating autophagy proteins such as LC3B, Beclin1, and ATG5 while inhibiting autophagic flux. CPS4 promoted AFB1 degradation, activated the p62-NRF2 antioxidant, and inhibited ROS/TRPML1 pathways, thereby reducing ROS production and inflammation and ultimately alleviating AFB1-induced autophagy and apoptosis. These findings supports the potential of probiotics to protect the male reproductive system from toxin damage.

Background: Feedback reports summarizing clinician performance are effective tools to improve antibiotic stewardship in the ambulatory setting, but few studies have evaluated their effectiveness for pediatric inpatients. We developed and implemented feedback reports reflecting electronically-derived measures of appropriate antibiotic choice and duration for community acquired pneumonia (CAP) and measured their impact on appropriate antibiotic use in children hospitalized for CAP. Methods: We performed a single center quasi-experimental study including children 6 months to 17 years hospitalized for CAP between 12/1/2021-11/30/2023. Children with chronic medical conditions, ICU stays >48 hours, and outside transfers were excluded. The intervention occurred in 11/2022 and included clinician education, a monthly group-level feedback report disseminated by email (Figure 1), and a monthly review of clinician performance during a virtual quality improvement meeting. Patient characteristics were compared using chi-square or Wilcoxon rank sum tests. Interrupted time series analysis (ITSA) was used to measure the immediate change in the proportion of CAP encounters receiving both the appropriate antibiotic choice and duration, as well as the change in slope from the preintervention to the postintervention periods. Choice and duration were analyzed separately using ITSA as a secondary analysis. Results: There were 817 CAP encounters, including 420 preintervention and 397 postintervention. Patients admitted in the postintervention period were older (median age 2 years vs 3 years, P=0.03), but otherwise there were no differences in race, ethnicity, sex, ICU admission, or complicated pneumonia. Preintervention, 52% of encounters received both the appropriate antibiotic choice and duration; 96% of encounters received the appropriate antibiotic choice and 54% received the appropriate duration. The ITSA demonstrated an immediate 16% increase in the proportion of patients receiving both appropriate antibiotic choice and duration (95% confidence interval, 1-31%; P = 0.047) and no significant further increase over time following the intervention (P = 0.84) (Figure 2). When antibiotic choice was analyzed separately by ITSA, there was no immediate change or change over time in the proportion of patients receiving the appropriate antibiotic choice. In the ITSA of duration alone, there was an immediate 17% increase in the proportion receiving the appropriate duration (95% confidence interval, 2-33%; P = 0.03) and no change over time. Conclusion: Feedback reports generated from electronically-derived metrics of antibiotic choice and duration, combined with ongoing clinician education, increased the proportion of children with CAP treated with the appropriate antibiotic duration. Electronic feedback reports are a scalable and impactful intervention to improve antibiotic use in children hospitalized with CAP.

Abstract Background The 9th edition of the lung cancer tumor‐node‐metastasis (TNM) staging introduced adjustments, including the reclassification of T1N1M0 patients from stage IIB to IIA. This update used data mostly from Asian populations. However, the applicability of these adjustments to Caucasian patients remains uncertain. Methods Stage II non‐small cell lung cancer (NSCLC) patients from the Surveillance, Epidemiology, and End Results (SEER) database were included. Kaplan–Meier analysis with log‐rank testing compared overall survival (OS) and cancer‐specific survival (CSS). Propensity score matching (PSM) balanced baseline characteristics. The least absolute shrinkage and selection operator (LASSO)‐based Cox analyses identified prognostic factors. Results Among 10,470 eligible stage II NSCLC patients (median age: 69 years; male: 53.1%), there were 2736 in stage IIA, 2112 in IIA New, and 5622 in IIB groups. Before PSM, survival outcomes of stage IIA New patients were similar to those of stage IIA patients but better than those of stage IIB. After PSM, stage IIA New and IIB patients showed similar survival rates (OS, p = 0.276; CSS, p = 0.565). Conversely, stage IIA New patients had worse outcomes than stage IIA patients (OS, p

IntroductionCross-sectional evidence suggests that sleep problems increased the risk of suicide during the 2019 coronavirus disease (COVID-19) pandemic. However, a lack of longitudinal studies examined the relationship between pre-COVID-19 sleep duration, chronotype and incident suicide during the COVID-19 pandemic. Thus, we examined these associations in a longitudinal study of medical students.MethodsFrom the Shantou College Student Sleep Cohort, a total of 333 first and second grade medical students (age 19.41 ± 0.82 years, female 61.26%), without suicidal ideation (SI) at pre-COVID-19 period, were followed up during the COVID-19 pandemic. Incident SI was defined by their response to the 9th question from the Beck Depression Inventory. Short sleep duration was defined as less than 7 h/night. The Morningness-Eveningness Questionnaire was used to evaluate the participants’ chronotype. Logistic regression with adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) was used to examine the association between sleep and SI.ResultsThe incidence of SI during the COVID-19 pandemic was 5.71%. Logistic regressions with confounding factors adjustment showed that both short sleep duration (AOR = 4.91, 95% CI = 1.16–20.74) and eveningness (AOR = 3.80, 95% CI = 1.08–13.30) in the pre-COVID-19 period were associated with increased risk of incident SI during the COVID-19 pandemic.ConclusionPre-COVID-19 short sleep duration and eveningness predict incident SI during the COVID-19 pandemic in medical students. Prolonging sleep duration may help to decrease SI during major public health crises.

Abstract BackgroundParental health literacy is important to children’s health and development, especially in the first 3 years. However, few studies have explored effective intervention strategies to improve parental literacy. ObjectiveThis study aimed to determine the effects of a WeChat official account (WOA)–based intervention on parental health literacy of primary caregivers of children aged 0-3 years. MethodsThis cluster randomized controlled trial enrolled 1332 caregiver-child dyads from all 13 community health centers (CHCs) in Minhang District, Shanghai, China, between April 2020 and April 2021. Participants in intervention CHCs received purposefully designed videos via a WOA, which automatically recorded the times of watching for each participant, supplemented with reading materials from other trusted web-based sources. The contents of the videos were constructed in accordance with the comprehensive parental health literacy model of WHO (World Health Organization)/Europe (WHO/Europe). Participants in control CHCs received printed materials similar to the intervention group. All the participants were followed up for 9 months. Both groups could access routine child health services as usual during follow-up. The primary outcome was parental health literacy measured by a validated instrument, the Chinese Parental Health Literacy Questionnaire (CPHLQ) of children aged 0-3 years. Secondary outcomes included parenting behaviors and children’s health outcomes. We used the generalized linear mixed model (GLMM) for data analyses and performed different subgroup analyses. The β coefficient, risk ratio (RR), and their 95% CI were used to assess the intervention’s effect. ResultsAfter the 9-month intervention, 69.4% (518/746) of caregivers had watched at least 1 video. Participants in the intervention group had higher CPHLQ total scores (β=2.51, 95% CI 0.12-4.91) and higher psychological scores (β=1.63, 95% CI 0.16-3.10) than those in the control group. The intervention group also reported a higher rate of exclusive breastfeeding (EBF) at 6 months (38.9% vs 23.44%; RR 1.90, 95% CI 1.07-3.38) and a higher awareness rate of vitamin D supplementation for infants younger than 6 months (76.7% vs 70.5%; RR 1.39, 95% CI 1.06-1.82). No significant effects were detected for the physical score on the CPHLQ, breastfeeding rate, routine checkup rate, and children’s health outcomes. Furthermore, despite slight subgroup differences in the intervention’s effects on the total CPHLQ score and EBF rate, no interaction effect was observed between these subgroup factors and intervention factors. ConclusionsUsing a WHO literacy model–based health intervention through a WOA has the potential of improving parental health literacy and EBF rates at 6 months. However, innovative strategies and evidence-based content are required to engage more participants and achieve better intervention outcomes.

The liver is essential for nutritional balance in fish, and liver damage in farmed fish often arises from factors like overfeeding, causing various health issues. Clinical observations indicate that liver diseases frequently involve spleen dysfunction, and there is evidence to suggest that the spleen has a significant impact on liver function. However, there has been no discussion on the role of the spleen in maintaining liver health in fish. To understand the role of fish spleen in liver metabolism, this study selected Nile tilapia (Oreochromis niloticus) as the experimental material and first established a tilapia splenectomy model. Various biochemical parameters of the liver and serum were measured, and the liver metabolism characteristics of the splenectomy group (SP group) and the sham operation group (SO group) were analyzed using metabolomics. After splenectomy, biochemical parameters of the liver and serum showed abnormalities, including significant increases in total cholesterol (T-CHO) and serum total bile acid (TBA) levels, alongside a significant decrease in liver TBA levels, suggesting impaired metabolic function and cholesterol deposition in the liver. Metabolomics analysis showed that metabolites such as lipids, lipid-like molecules, and organic acids and derivatives were differentially regulated between the SO and SP group. KEGG analysis showed that differential metabolites were enriched in lipid metabolism and amino acid metabolism. The metabolic pathway analysis of differential metabolites showed that after splenectomy, the low-activity urea cycle in the liver may accelerate lipid synthesis, while low concentrations of aromatic amino acids and taurine may inhibit lipid catabolism. These results indicate that after splenectomy, the liver metabolic capacity is impaired, which causes abnormal lipid metabolism by interfering with amino acid metabolism, making splenectomy tilapia liver at risk of liver disease, including cholesterol deposition, hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Our results show that the spleen is involved in regulating liver lipid and amino acid metabolism, and the spleen may interfere with lipid metabolism by regulating liver amino acid metabolism. Our data can provide support for further research on liver and spleen functions and the immune-nutrient metabolism mechanisms in fish, as well as new ideas for healthy fish farming.

AimsPersistent uncertainties exist surrounding the therapeutic drug monitoring (TDM) of adalimumab in clinical settings. To address these issues, we conducted a systematic review to assess the current evidence regarding the benefits of TDM for adalimumab.MethodsPubMed, EMBASE, and Cochrane Databases were searched from inception to October 2022. The trials regarding to the list three key questions were considered: 1) Could routine proactive TDM assist in improving outcomes in patients receiving adalimumab? 2) Could reactive TDM assist in guiding subsequent treatment strategies for patients with treatment failure to adalimumab? 3) Could TDM assist in informing dose reduction or discontinuation in patients with low disease activity or in remission treated with adalimumab? Two reviewers independently selected the studies and extracted the data. Meta-analysis was performed to calculate the relative risk (RR) and 95% confidence interval (CI).ResultsA total of 9 studies was included in this review. For proactive TDM, meta-analysis indicated that proactive TDM (n = 163/257, 63.42%) showed no significant superiority over reactive TDM and/or conventional management (n = 336/606, 55.44%) in achieving and/or maintaining clinical remission by random effects model (RR: 1.24, 95% CI 0.98–1.58, I2 = 73%). There were three studies that supporting the reactive TDM, low drug levels in the absence of anti-drug antibodies (ADA) strongly indicate the need for dose intensification, and infliximab is a feasible choice for patients with low drug levels and ADA positivity. While swapping to another class should be considered in patients with adequate drug levels. In addition, TDM can help clinicians optimize dosing schedules and prevent overtreatment in patients who have achieved low disease activity and sufficient drug concentrations, with no predictive value for successful adalimumab discontinuation.ConclusionCurrent evidence suggests that proactive TDM is numerically but not statistically significant superiority over reactive TDM and/or conventional management. Reactive TDM can aid in understanding treatment failure and developing subsequent therapy. For patients reaching low disease activity and remission, TDM can help successful dose reduction, while it cannot inform the successful drug discontinuation. However, existing trials are limited, and more well-designed trials are necessary to clarify the role of TDM in adalimumab treatment.

IntroductionThis study aimed to explore the influence of Intimate Partner Violence (IPV) on depression, the mediating role of social support, and the moderating role of the Big Five personality traits in the relationship between social support and depression.MethodsParticipants were recruited from Mainland China, using a stratified random sampling and quota sampling method. From June to August 2022, a diverse group of 21,916 participants (ranging from 12 to 100 years old) completed the Intimate Partner Violence Scale, Patient Health Questionnaire, Perceived Social Support Scale, and Big Five Inventory-Short Version.ResultsIPV was significantly positively correlated with depression and significantly negatively correlated with perceived social support. Perceived social support plays a mediating role in the link between IPV and depression.DiscussionHealthcare workers should assess social support and provide adequate care or recommendations for increasing social support when patients with IPV report depressive symptoms. Patients can be coached by professionals to improve their resiliency by developing or nurturing more optimistic personality traits.

Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates a variety of key processes like inhibiting angiogenesis by reducing vascular endothelial growth factor levels and protecting the blood-retinal barrier (BRB) integrity by enhancing tight junction proteins and pericyte coverage. Melatonin also maintains cell health by modulating autophagy via the Sirt1/mTOR pathways, reduces inflammation, promotes antioxidant enzyme activity, and regulates intraocular pressure fluctuations. Additionally, melatonin protects retinal ganglion cells by modulating aging and inflammatory pathways. Understanding melatonin's multifaceted functions in ocular health could expand the knowledge of ocular pathogenesis, and shed new light on therapeutic approaches in ocular diseases. In this review, we summarize the current evidence of ocular functions and therapeutic potential of melatonin and describe its roles in angiogenesis, BRB integrity maintenance, and modulation of various eye diseases, which leads to a conclusion that melatonin holds promising treatment potential for a wide range of ocular health conditions.

Nuclear progesterone receptor (nPR) is a member of the nuclear receptor family known to play a critical role in gonad development, gametogenesis, and ovulation in vertebrates, and also important in pregnancy maintenance and parturition in mammals. However, its biological functions in ovoviviparity teleosts are less clear. This study aimed to determine the possible role of nPR in fish oogenesis, pregnancy and parturition using black rockfish as a model. The npr, which consists of 2076 bp and codes for a 691 amino acids protein, was cloned. Phylogenetic analysis revealed that the nPR of black rockfish is more conserved in teleosts. Quantitative real-time PCR analyses in various tissues showed that npr was mainly detected in the pituitary followed by the ovary, testis and brain, while it was very low or undetectable in the spleen, head kidney, intestine and gill. During the gonadal development process, the npr level showed no variation in the ovary. In testis, the mRNA level of npr showed varied expression in different developmental stages with the highest level in the maturation stage. Detection of npr expression during fertilization and the perinatal period further showed that nPR may play important roles in the regulation of pregnancy and the parturition. In situ hybridization further revealed that npr mRNA was observed in the follicular cell layer during the perinatal period. The results from in vitro experiments showed that npr level was significantly downregulated when the primary cultured follicular cells during vitellogenesis (stage Ⅳ) were exposed to hCG. Studies using primary culture of black rockfish ovarian cells during the perinatal period, treated in vitro revealed that genes related to PGs synthesis (pla2g4a, cox2) and matrix metalloproteinases (mmp2, mmp9) were upregulated in response to 17,20β-P. However, treatment with 17,20β-P downregulated npr expression. In conclusion, these data suggest that nPR plays an essential role in fertilization, pregnancy maintenance and parturition in black rockfish.

ObjectivesThis study aimed to fill the data gap of the course of renal function decline in old age and explore changes in renal function across different health states with increasing age.MethodsThis observational, retrospective, single-center cohort study included 5,112 Chinese older adults (3,321 men and 1,791 women, range 60–104 years). The individual rate of estimated glomerular filtration rate (eGFR) decline was analyzed using linear mixed-effects model to account for repeated measures over the years.ResultsThe median age was 66 years, median BMI was 24.56 kg/m2, and median eGFR was 89.86 mL/min.1.73 m2. For every 1-year increase in age, women’s eGFR decreased by 1.06 mL/min/1.73 m2 and men’s by 0.91 mL/min/1.73 m2. We observed greater age-related eGFR decline in men and women with high systolic blood pressure (SBP). Men with high triglyceride (TG), high low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C), had greater age-related eGFR decline. In women, different BMI groups showed significant differences in age-related eGFR decline, with the highest decline in those with obesity. Additionally, participants with normal baseline eGFR had a faster age-related decline than those with low baseline eGFR.ConclusionThe eGFR declined linearly with age in Chinese older adults, with women exhibiting a slightly faster decline than men. Both men and women should be cautious of SBP. Older adults with normal baseline renal function experienced a faster eGFR decline. Men with high TG, LDL-C, and low HDL-C levels, as well as obese women, should be vigilant in monitoring renal function.

Radiotherapy (RT) and immune checkpoint inhibitor (ICI) are important treatments for esophageal cancer. Some studies have confirmed the safety and effectiveness of using RT in combination with ICI, while serious side effects have been exhibited by some patients. We report a patient with metastatic esophageal cancer who received RT combined with ICI. The patient experienced severe thrombocytopenia, and treatment with thrombopoietin and corticosteroids were ineffective. Finally, the patient developed abscopal hyperprogression outside the radiation field. Interestingly, next-generation sequencing revealed increased JAK2 gene copies in the surgical slices. The JAK2/STAT3 pathway is involved in the regulation of megakaryocyte development. Recurrent thrombocytopenia may activate the JAK2/STAT3 pathway, leading to megakaryocyte differentiation and platelet biogenesis. However, persistent activation of the JAK2/STAT3 pathway has been associated with immune ICI resistance and tumor progression. This case indicates that thrombocytopenia and increased JAK2 gene copies may be risk factors for poor prognosis after ICI and RT treatment.

Oral biofilm is the leading cause of dental caries, which is difficult to completely eradicate because of the complicated biofilm structure. What's more, the hypoxia environment of biofilm and low water-solubility of conventional photosensitizers severely restrict the therapeutic effect of photodynamic therapy (PDT) for biofilm. Although conventional photosensitizers could be loaded in nanocarriers, it has reduced PDT effect because of aggregation-caused quenching (ACQ) phenomenon. In this study, we fabricated an oxygen self-sufficient nanodroplet (PFC/TPA@FNDs), which was composed of fluorinated-polymer (FP), perfluorocarbons (PFC) and an aggregation-induced emission (AIE) photosensitizer (Triphenylamine, TPA), to eradicate oral bacterial biofilm and whiten tooth. Fluorinated-polymer was synthesized by polymerizing (Dimethylamino)ethyl methacrylate, fluorinated monomer and 1-nonanol monomer. The nanodroplets could be protonated and behave strong positive charge under bacterial biofilm acid environment promoting nanodroplets deeply penetrating biofilm. More importantly, the nanodroplets had extremely high PFC and oxygen loading efficacy because of the hydrophobic affinity between fluorinated-polymer and PFC to relieve the hypoxia environment and enhance PDT effect. Additionally, compared with conventional ACQ photosensitizers loaded system, PFC/TPA@FNDs could behave superior PDT effect to ablate oral bacterial biofilm under light irradiation due to the unique AIE effect. In vivo caries animal model proved the nanodroplets could reduce dental caries area without damaging tooth structure. Ex vivo tooth whitening assay also confirmed the nanodroplets had similar tooth whitening ability compared with commercial tooth whitener H2O2, while did not disrupt the surface microstructure of tooth. This oxygen self-sufficient nanodroplet provides an alternative visual angle for oral biofilm eradication in biomedicine.

Background The prevalence, Medicaid use and mortality risk associated with low forced expiratory volume in 1 s (FEV1) among young adults aged 20–35 years are not well understood, despite its potential implications for the development of chronic pulmonary disease and overall prognosis.Methods A retrospective cohort study was conducted among young adults aged 20–35 years old, using data from the National Health and Nutrition Examination Survey, National Death Index and Centers for Medicare & Medicaid Services. Participants were categorised into a low FEV1 group (pre-bronchodilator FEV1%pred

Intraoperative remifentanil administration has been linked to increased postoperative pain sensitivity. Recent studies have identified the involvement of euchromatic histone-lysine N-methyltransferase 2 (Ehmt2/G9a) in neuropathic pain associated with the transcriptional silencing of many potassium ion channel genes. This study investigates whether G9a regulates the potassium sodium-activated channel subfamily T member 1 (Slo2.2) in remifentanil-induced post-incisional hyperalgesia (RIH) in rodents. We performed remifentanil infusion (1 μg·kg-1·min-1 for 60 min) followed by plantar incision to induce RIH in rodents. Our results showed that RIH was accompanied by increased G9a and H3K9me2 production and decreased Slo2.2 expression 48 h postoperatively. Deletion of G9a rescued Slo2.2 expression in DRG and reduced RIH intensity. Slo2.2 overexpression also reversed this hyperalgesia phenotype. G9a overexpression decreased Slo2.2-mediated leak current and increased excitability in the small-diameter DRG neurons and laminal II small-diameter neurons in the spinal dorsal horn, which was implicated in peripheral and central sensitization. These results suggest that G9a contributes to the development of RIH by epigenetically silencing Slo2.2 in DRG neurons, leading to decreased central sensitization in the spinal cord. The findings may have implications for the development of novel therapeutic targets for the treatment of postoperative pain.

Sleep fragmentation (SF) is a common sleep problem experienced during the perioperative period by older adults, and is associated with postoperative cognitive dysfunction (POCD). Increasing evidence indicates that delta-wave activity during non-rapid eye movement (NREM) sleep is involved in sleep-dependent memory consolidation and that hippocampal theta oscillations are related to spatial exploratory memory. Recovery sleep (RS), a self-regulated state of sleep homeostasis, enhances delta-wave power and memory performance in sleep-deprived older mice. However, it remains unclear whether RS therapy has a positive effect on cognitive changes following SF in older mouse models. Therefore, this study aimed to explore whether preoperative RS can alleviate cognitive deficits in aged mice with SF. A model of preoperative 24-h SF combined with exploratory laparotomy-induced POCD was established in 18-month-old mice. Aged mice were treated with preoperative 6-h RS following SF and postoperative 6-h RS following surgery, respectively. The changes in hippocampus-dependent cognitive function were investigated using behavioral tests, electroencephalography (EEG), local field potential (LFP), magnetic resonance imaging, and neuromorphology. Mice that underwent 24-h SF combined with surgery exhibited severe spatial memory impairment; impaired cognitive performance could be alleviated by preoperative RS treatment. In addition, preoperative RS increased NREM sleep; enhanced EEG delta-wave activity and LFP theta oscillation in the hippocampal CA1; and improved hippocampal perfusion, microstructural integrity, and neuronal damage. Taken together, these results provide evidence that preoperative RS may ameliorate the severity of POCD aggravated by SF by enhancing delta slow-wave activity and hippocampal theta oscillation, and by ameliorating the reduction in regional cerebral blood flow and white matter microstructure integrity in the hippocampus.

ObjectiveTo analyze protective effect of seasonal influenza vaccination among primary and junior middle school students during influenza outbreak in schools during 2022 – 2023 for developing influenza vaccination strategies. MethodsA retrospective cohort study was conducted among 4 087 students in 64 classes of 5 preschool/primary/junior middle schools with influenza outbreaks (at least two cases diagnosed in a class) during February – April 2023 in Sichuan province. The parents of the students were asked to answer an online questionnaire about the students′ information on demographics, influenza situation, and the status of influenza vaccination. The cases′ laboratory diagnosis and the students′ detailed information on seasonal vaccination were further checked in the National Infectious Disease Surveillance Information System and the Sichuan Province Planned Immunization Information Management System using Identification Card Numbers of the students. Multivariate logistic regression was adopted to calculate adjusted relative risk (RR) of influenza of the influenza vaccinees for the estimation of adjusted vaccine effectiveness (VEadj) of influenza vaccination with following formula: VEadj = (1 – RRadj) × 100%. ResultsAmong all the students surveyed, 1 352 (33.1%) had influenza onset during the outbreak period from April to June 2023, including 292 laboratory confirmed, 659 clinically diagnosed, and 401 suspected cases. There were 19.0% of students had receiving seasonal influenza vaccination, the VEadj (95% confidence interval [95%CI]) of flu vaccination was 26.0% (0.6% – 44.9%) for clinically diagnosed and laboratory confirmed cases; stratified analyses showed that for all the vaccinees with the interval time of within 14 – 120 days and within 121 – 180 days between the vaccination and influenza onset, the VEadj (95%CI) were 78.3% (59.8% – 88.3%) and 58.6% (35.6% – 73.4%); for the vaccinees with the same two interval periods but receiving quadrivalent flu vaccine, the VEadj (95%CI) were 81.4% (63.8% – 90.4%) and 62.3% (40.7% – 76.0%) and the VEadj (95%CI) were 73.4% (12.1% – 92.0%) and 87.1% (74.7% – 93.4%) for the vacinees with confirmed influenza A(H1N1) infection and the same two interval periods mentioned above, respectively. No significant protective effect of influenza vaccine for the vaccinees with the interval time of more than 180 days time.ConclusionInfluenza vaccination is of certain protective effect on preventing influenza infection among preschool/primary/junior middle school students, and the protective effect is obvious within 6 months after the seasonal vaccination. The results suggest influenza vaccination should be promoted among primary and junior middle school students to prevent influenza outbreaks in schools.

Abstract Amino acid/auxin permease (AAAP) genes encode a large family of protein transporters that play important roles in various aspects of plant growth and development. Here, we performed genome-wide identification of members in the foxtail millet (Setaria italica L.) AAAP family (SiAAAP) and their saline-alkali stress-induced expression patterns, resulting in the identification of 65 SiAAAP genes, which could be divided into eight subfamilies. Except for SiAAAP65, the remaining 64 genes were located on nine chromosomes of foxtail millet. Gene structure and conserved motif analyses indicated that the members in the same subfamily are highly conserved. Gene duplication event analysis suggested that tandem duplication may be the main factor driving the expansion of this gene family, and Ka/Ks analysis indicated that all the duplicated genes have undergone purifying selection. Transcriptome analysis showed differential expression of SiAAAPs in roots, stems, leaves, and tassel inflorescence. Analysis of cis-acting elements in the promoter indicated that SiAAAPs contain stress-responsive cis-acting elements. Under saline-alkali stress, qRT-PCR analysis showed that SiAAP3, SiLHT2, and SiAAP16 were differentially expressed between salt-alkali tolerant millet variety JK3 and salt-alkali sensitive millet variety B175. These results suggest that these genes may be involved in or regulate the response to saline-alkali stress, providing a theoretical basis for further studying the function of SiAAAPs.

Abstract Different aromatic components do indeed give different tea flavors. There is still little research on whether there is a certain regularity in the combination and content of aromatic components in different aroma types of Phoenix Dancong (PDC) tea. This potential regularity may be a key factor in unraveling the relationship between reproduction and evolution in PDC tea. Here, the 5 kinds of these 4 aroma types PDC tea (Zhuye, Tuofu, Jianghuaxiang, Juduo, Yashixiang) were used as research materials in this study, the headspace solid-phase microextraction combined with gas chromatography–mass spectrometry was used to analyze the aromatic components of these PDC teas. The results showed a total of 36 aromatic components identified in this study. When conducting cluster analysis, it was found that similarity degree arrangement sequence of 5 PDC teas was Juduo, Tuofu, Yashixiang, Zhuye and Jianghuaxiang. Among these aromatic components, the 7,9-Di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione, the 2-Cyclopenten-1-one, 3-methyl-2-(2-pentenyl)-,(Z)-, the 2,4-Di-tert-butylphenol, the 3,7-dimethyl-1,5,7-Octatrien-3-ol, and the 2-Furanmethanol,5-ethenyltetrahydro-.alpha.,.alpha.,5-trimethyl-,cis- are common to 5 PDC teas. This study aims to elucidate the similarities in the aromatic components of 5 PDC teas, revealing the major aroma-endowed substances of various aroma, and providing theoretical reference for further exploring the relationship between aroma type discrimination, variety selection, and evolution of PDC teas.

Abstract Polygenic risk scores (PRS) have shown successes in clinics, but most PRS methods focus only on participants with distinct primary continental ancestry without accommodating recently-admixed individuals with mosaic continental ancestry backgrounds for different segments of their genomes. Here, we develop GAUDI, a novel penalized-regression-based method specifically designed for admixed individuals. GAUDI explicitly models ancestry-differential effects while borrowing information across segments with shared ancestry in admixed genomes. We demonstrate marked advantages of GAUDI over other methods through comprehensive simulation and real data analyses for traits with associated variants exhibiting ancestral-differential effects. Leveraging data from the Women’s Health Initiative study, we show that GAUDI improves PRS prediction of white blood cell count and C-reactive protein in African Americans by > 64% compared to alternative methods, and even outperforms PRS-CSx with large European GWAS for some scenarios. We believe GAUDI will be a valuable tool to mitigate disparities in PRS performance in admixed individuals.

Abstract Objective Physical exercise has the potential to mitigate addictive behaviors and relevant health issues. However, the nighttime exercise has not been studied regarding this research topic. This study aims to explore the association between nocturnal physical exercise and problematic smartphone use before sleep, as well as related health issues. Methods To explore the association between nighttime physical exercise and problematic smartphone use before sleep as well as related health issues, we conducted a cross-sectional survey among 1,334 college students. Their daily exercise behaviors (including timeframe, rationale, frequency, and duration), smartphone use before sleep, sleep quality, smartphone addiction, anxiety, and depression were measured by questionnaires. The associations were assessed using generalized linear models. Results Our findings indicate that nearly 70% of participants chose to perform exercise at nighttime. Among these individuals who exercised at nighttime, the frequency and duration of nighttime exercise were significantly associated with decreased probabilities of smartphone use before sleep. Additionally, the frequency and duration of nighttime exercise were associated with lower levels of smartphone addiction and anxiety disorders. Conclusion Nighttime Exercise behaviors can effectively reduce sleep delays caused by problematic smartphone use before bedtime. These findings contribute to understanding the potential effects of nighttime exercise on problematic smartphone use and relevant health issues. Future research should employ more precise methodologies to examine these associations.

Grid frequency dynamic is dominant by synchronous generators (SGs), but it is more and more obviously affected the voltage-source-converter-based (VSC-based) devices. This paper presents a modelling method of the real equivalent inertia of the VSynC-based VSC and an analysis approach for grid frequency dynamics. In this paper, the virtual synchronous control (VSynC)-based VSC is taken as an example. Firstly, grid frequency dynamic is introduced with and without considering energy constraints and cascaded control of the VSynC-based VSC, respectively. Then the swing equation model is established to study the real inertial characteristic of the VSynC-based VSC, which poses main effect on grid frequency dynamics. Based on the swing equation model, the real equivalent inertia characteristic is deduced under the consideration of the energy constraints and cascaded control dynamics of DC voltage control, and it is recognized as a transfer function, rather than the constant value like traditional SGs. Moreover, under the effect of the transfer-function-based inertia of the VSynC-based VSC, the bode-diagram-based analysis method is proposed in this paper to discuss the frequency dynamics of the power system with both SGs and VSynC-based VSCs. The zero-crossing frequency and phase margin in bode diagrams are used to evaluate the major characteristics of grid frequency, i.e. the rate of change of frequency (ROCOF) and nadir (the max deviation). Finally, case studies are implemented based on New England 39 Bus System to validate the correctness and effectiveness of the proposed modelling and analysis method.

Abstract Background In the context of increasing population aging, ongoing drug-resistant pathogens and the COVID-19 epidemic, the changes in the epidemiological and clinical characteristics of patients with pneumonia remain unclear. This study aimed to assess the trends in hospitalization, case fatality, comorbidities, and isolated pathogens of pneumonia-related adult inpatients in Guangzhou during the last decade. Methods We retrospectively enrolled hospitalized adults who had doctor-diagnosed pneumonia in the First Affiliated Hospital of Guangzhou Medical University from January 1, 2013 to December 31, 2022. A natural language processing system was applied to automatically extract the clinical data from electronic health records. We evaluated the proportion of pneumonia-related hospitalizations in total hospitalizations, pneumonia-related in-hospital case fatality, comorbidities, and species of isolated pathogens during the last decade. Binary logistic regression analysis was used to assess predictors for patients with prolonged length of stay (LOS). Results A total of 38,870 cases were finally included in this study, with 70% males, median age of 64 (53, 73) years and median LOS of 7.9 (5.1, 12.8) days. Although the number of pneumonia-related hospitalizations showed an upward trend, the proportion of pneumonia-related hospitalizations decreased from 199.6 per 1000 inpatients in 2013 to 123.4 per 1000 in 2021, and the case fatality decreased from 50.2 per 1000 in 2013 to 23.9 per 1000 in 2022 (all P

Abstract Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous H2O2 to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT. Specifically, rationally designed 2D Pd@Au nanosheets (NSs) enable consistent enzymatic conversion of endogenous H2O2 into O2 to overcome hypoxia-induced RIT resistance. Furthermore, partially coated Au layer afford NIR-II responsiveness and moderate photothermal treatment that augmenting their enzymatic functionality. This approach with dual-effect paves the way for reshaping TME and consequently facilitating the brachytherapy ablation of cancer. Our work offers a significant advancement in the integration of catalytic nanomedicine and nuclear medicine, with the overarching goal of amplifying the clinical benefits of RIT-treated patients. Graphical abstract

Background & Aims: The functional maturation of the liver largely occurs after birth. In the early stages of life, the liver of a newborn encounters enormous high-fat metabolic stress caused by the consumption of breast milk. It is unclear how the maturing liver adapts to high lipid metabolism. Liver sinusoidal endothelial cells (LSECs) play a fundamental role in establishing liver vasculature and are decorated with many glycoproteins on their surface. The Slc35a1 gene encodes a cytidine-5'-monophosphate (CMP)-sialic acid transporter responsible for transporting CMP-sialic acids between the cytoplasm and the Golgi apparatus for protein sialylation. This study aimed to determine whether endothelial sialylation plays a role in hepatic vasculogenesis and functional maturation. Methods: Endothelial-specific Slc35a1 knockout mice were generated. Liver tissues were collected for histologic analysis, lipidomic profiling, RNA sequencing, confocal immunofluorescence, and immunoblot analyses. Results: Endothelial Slc35a1-deficient mice exhibited excessive neonatal hepatic lipid deposition, severe liver damage, and high mortality. Endothelial deletion of Slc35a1 led to sinusoidal capillarization and disrupted hepatic zonation. Mechanistically, vascular endothelial growth factor receptor 2 (VEGFR2) in LSECs was desialylated and VEGFR2 signaling was enhanced in Slc35a1-deficient mice. Inhibition of VEGFR2 signaling by SU5416 alleviated lipid deposition and restored hepatic vasculature in Slc35a1-deficient mice. Conclusions: Our findings suggest that sialylation of LSECs is critical for maintaining hepatic vascular development and lipid homeostasis. Targeting VEGFR2 signaling may be a new strategy to prevent liver disorders associated with abnormal vasculature and lipid deposition.

Reclamation space, as an important part connecting land and sea, is a key link in land-sea coordination. Taking Shenzhen as an example, by combing the Landsat remote sensing image data from 1980 to 2020, analyzing the scale of reclamation and the change of coastline and interpreting the background, it is found that the reclamation history in Shenzhen has gone through four stages: independent construction by harbor enterprises under pilot development (1980—1986), expansion of local industrial infrastructure in the separation of government and enterprise (1986—1996), strengthening of the dual role of the government under resource shortage (1996—2010), and consideration of multiple benefits in optimization of stock space (2010—2020). The total reclamation area reaches 91.68 km2, the retention rate of natural coastline has decreased by 49.92%, and the continuous years of reclamation have had a negative impact on the ecological security of the coastal zone. On this basis, this paper points out that the government, as the benefit-oriented policy subject, has had an important impact on its own, corporate and public behavior on reclamation. Finally, based on the experience gained from Shenzhen, the spatial development of other coastal cities should focus on the ecological restoration and benefit compensation of historical reclamation projects and on the trade-off between economic and ecological benefits of new reclamation projects.

In order to further understand the characteristics of phytoplankton community in the sea area near Changbiao Island in Xiapu, the data of phytoplankton and water environment from four cruises in May (spring), September (summer), December (autumn) and February (winter) in 2019—2020 were analyzed, and the characteristics of phytoplankton community structure were analyzed. The main environmental factors affecting the structure of phytoplankton community were studied by redundancy analysis. The results showed that there were 170 species of phytoplankton in 60 genera, 48 genera and 131 species of diatoms, 26 species of dinoflagellates in 10 genera, 2 species of cyanobacteria in 1 genera and 1 species of diatoms in 1 genera. Phytoplankton are mainly coastal wide-temperature and wide-salt species and warm water species. There are 13 dominant species throughout the year. In spring, Prorocentrum donghaiense and Noctiluca are the main species, and Skeletonema costatum and Siegesbeckia qiongshi are the main species in summer, autumn and winter. The spatial distribution of phytoplankton abundance shows a trend of high nearshore, low farshore, low in the south, and high in the north. Seasonal variation of phytoplankton is mainly affected by water temperature. Appropriate temperature and nutrients in spring and summer promote a large increase in phytoplankton, while autumn and winter are mainly affected by temperature. Now in spring and summer, the coastal nuclear power station of Changbiao Island in Xiapu should focus on monitoring the occurrence of red tide in spring and summer.