Search

Abstract Macrophage-orchestrated inflammation contributes to multiple diseases including sepsis. However, the underlying mechanisms remain to be defined clearly. Here, we show that macrophage TP53-induced glycolysis and apoptosis regulator (TIGAR) is up-regulated in murine sepsis models. When myeloid Tigar is ablated, sepsis induced by either lipopolysaccharide treatment or cecal ligation puncture in male mice is attenuated via inflammation inhibition. Mechanistic characterizations indicate that TIGAR directly binds to transforming growth factor β-activated kinase (TAK1) and promotes tumor necrosis factor receptor-associated factor 6-mediated ubiquitination and auto-phosphorylation of TAK1, in which residues 152-161 of TIGAR constitute crucial motif independent of its phosphatase activity. Interference with the binding of TIGAR to TAK1 by 5Z-7-oxozeaenol exhibits therapeutic effects in male murine model of sepsis. These findings demonstrate a non-canonical function of macrophage TIGAR in promoting inflammation, and confer a potential therapeutic target for sepsis by disruption of TIGAR-TAK1 interaction.

Abstract Project Optimus is a US Food and Drug Administration Oncology Center of Excellence initiative aimed at reforming the dose selection and optimization paradigm in oncology drug development. This project seeks to bring together pharmaceutical companies, international regulatory agencies, academic institutions, patient advocates, and other stakeholders. Although there is much promise in this initiative, there are several challenges that need to be addressed, including multidimensionality of the dose optimization problem in oncology, the heterogeneity of cancer and patients, importance of evaluating long‐term tolerability beyond dose‐limiting toxicities, and the lack of reliable biomarkers for long‐term efficacy. Through the lens of Totality of Evidence and with the mindset of model‐informed drug development, we offer insights into dose optimization by building a quantitative knowledge base integrating diverse sources of data and leveraging quantitative modeling tools to build evidence for drug dosage considering exposure, disease biology, efficacy, toxicity, and patient factors. We believe that rational dose optimization can be achieved in oncology drug development, improving patient outcomes by maximizing therapeutic benefit while minimizing toxicity.

Abstract In this study, we investigated the codon bias of twelve mitochondrial core protein coding genes (PCGs) in eight Pleurotus strains, two of which are from the same species. The results revealed that the codons of all Pleurotus strains had a preference for ending in A/T. Furthermore, the correlation between codon base compositions and codon adaptation index (CAI), codon bias index (CBI) and frequency of optimal codons (FOP) indices was also detected, implying the influence of base composition on codon bias. The two P. ostreatus species were found to have differences in various base bias indicators. The average effective number of codons (ENC) of mitochondrial core PCGs of Pleurotus was found to be less than 35, indicating strong codon preference of mitochondrial core PCGs of Pleurotus. The neutrality plot analysis and PR2-Bias plot analysis further suggested that natural selection plays an important role in Pleurotus codon bias. Additionally, six to ten optimal codons (ΔRSCU > 0.08 and RSCU > 1) were identified in eight Pleurotus strains, with UGU and ACU being the most widely used optimal codons in Pleurotus. Finally, based on the combined mitochondrial sequence and RSCU value, the genetic relationship between different Pleurotus strains was deduced, showing large variations between them. This research has improved our understanding of synonymous codon usage characteristics and evolution of this important fungal group.

Abstract A flexible or planar eddy current probe with a differential structure can suppress the lift-off noise during the inspection of defects. However, the extent of the lift-off effect on differential probes, including different coil structures, varies. In this study, two planar eddy current probes with differential pickup structures and the same size, Koch and circular probes, were used to compare lift-off effects. The eddy current distributions of the probes perturbed by 0° and 90° cracks were obtained by finite element analysis. The analysis results show that the 90° crack can impede the eddy current induced by the Koch probe even further at relatively low lift-off distance. The peak-to-peak values of the signal output from the two probes were compared at different lift-off distances using finite element analysis and experimental methods. In addition, the effects of different frequencies on the lift-off were studied experimentally. The results show that the signal peak-to-peak value of the Koch probe for the inspection of cracks in 90° orientation is larger than that of the circular probe when the lift-off distance is smaller than 1.2 mm. In addition, the influence of the lift-off distance on the peak-to-peak signal value of the two probes was studied via normalization. This indicates that the influence becomes more evident with an increase in excitation frequency. This research discloses the lift-off effect of differential planar eddy current probes with different coil shapes and proves the detection merit of the Koch probe for 90° cracks at low lift-off distances.

Abstract The purpose of this study was to explore the diagnostic implications of ubiquitination-related gene signatures in Alzheimer's disease. In this study, we first collected 161 samples from the GEO database (including 87 in the AD group and 74 in the normal group). Subsequently, through differential expression analysis and the iUUCD 2.0 database, we obtained 3450 Differentially Expressed Genes (DEGs) and 806 Ubiquitin-related genes (UbRGs). After taking the intersection, we obtained 128 UbR-DEGs. Secondly, by conducting GO and KEGG enrichment analysis on these 128 UbR-DEGs, we identified the main molecular functions and biological pathways related to AD. Furthermore, through the utilization of GSEA analysis, we have gained insight into the enrichment of functions and pathways within both the AD and normal groups. Further, using lasso regression analysis and cross-validation techniques, we identified 22 characteristic genes associated with AD. Subsequently, we constructed a logistic regression model and optimized it, resulting in the identification of 6 RUbR-DEGs: KLHL21, WDR82, DTX3L, UBTD2, CISH, and ATXN3L. In addition, the ROC result showed that the diagnostic model we built has excellent accuracy and reliability in identifying AD patients. Finally, we constructed a lncRNA-miRNA-mRNA (competing endogenous RNA, ceRNA) regulatory network for AD based on six RUbR-DEGs, further elucidating the interaction between UbRGs and lncRNA, miRNA. In conclusion, our findings will contribute to further understanding of the molecular pathogenesis of AD and provide a new perspective for AD risk prediction, early diagnosis and targeted therapy in the population.

Abstract It is commonly assumed that gastrointestinal cancer is the most common form of cancer across the globe and is the leading contributor to cancer-related death. The intricate mechanisms underlying the growth of GI cancers have been identified. It is worth mentioning that both non-coding RNAs (ncRNAs) and certain types of RNA, such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), can have considerable impact on the development of gastrointestinal (GI) cancers. As a tumour suppressor, in the group of short non-coding regulatory RNAs is miR-34a. miR-34a silences multiple proto-oncogenes at the post-transcriptional stage by targeting them, which inhibits all physiologically relevant cell proliferation pathways. However, it has been discovered that deregulation of miR-34a plays important roles in the growth of tumors and the development of cancer, including invasion, metastasis, and the tumor-associated epithelial-mesenchymal transition (EMT). Further understanding of miR-34a’s molecular pathways in cancer is also necessary for the development of precise diagnoses and effective treatments. We outlined the most recent research on miR-34a functions in GI cancers in this review. Additionally, we emphasize the significance of exosomal miR-34 in gastrointestinal cancers.

IntroductionScalp arteriovenous fistula (AVF) is a rare and intricate vascular anomaly characterized by a direct connection between an artery and a vein, without an intervening capillary system. This anomaly can induce significant local hemodynamic changes and is associated with various complications, such as pain, a pulsatile mass, increasing swelling, and venous hypertension skin ulcerations which may be non-healing. This study aimed to evaluate the efficacy and safety of interventional embolization treatments for scalp AVF at Shandong Provincial Hospital.MethodsThis retrospective clinical analysis assessed 21 patients who underwent interventional embolization between 2018 and 2024. Patients included were those treated in the vascular surgery department at Shandong Provincial Hospital, who had comprehensive medical records and follow-up data. Treatment methods, outcomes, and complications were thoroughly analyzed through patient medical records.ResultsAmong the patients studied, direct puncture was the most prevalent treatment method, employed in 42.86% (9/21) of cases, followed by various combinations of arterial, venous, and direct approaches. Ethanol, used in 85.71% (18/21) of the cases, demonstrated its broad efficacy and application in clinical settings. Immediate imaging post-treatment confirmed a cure rate of 85.71% (18/21). The main postoperative complications included swelling, with some patients also experiencing nodules, scabbing, or hair loss.ConclusionInterventional embolization has proven to be a safe and effective method for managing scalp AVF, significantly minimizing complications. Future research should focus on further optimizing these treatment methods to enhance efficacy and improve patient quality of life.

The receptive field (RF) plays a crucial role in convolutional neural networks (CNNs) because it determines the amount of input information that each neuron in a CNN can perceive, which directly affects the feature extraction ability. As the number of convolutional layers in CNNs increases, there is a decay of the RF according to the two-dimensional Gaussian distribution. Thus, an effective receptive field (ERF) can be used to characterize the available part of the RF. The ERF is calculated by the kernel size and layer number within the neural network architecture. Currently, ERF calculation methods are typically applied to single-channel input data that are both independent and identically distributed. However, such methods may result in a loss of effective information if they are applied to more general (i.e., multi-channel) datasets. Therefore, we proposed a multi-channel ERF calculation method. By conducting a series of numerical experiments, we determined the relationship between the ERF and the convolutional kernel size in conjunction with the layer number. To validate the new method, we used the recently published global wave surrogate model for climate simulation (GWSM4C) and its accompanying dataset. According to the newly established relationship, we refined the kernel size and layer number in each neural network of the GWSM4C to produce the same ERF but lower RF attenuation rates than those of the original version. By visualizing the gradient map at several points in West African and East Pacific areas, the high gradient value regions confirmed the known swell sources, which indicated effective feature extraction in these areas. Furthermore, the new version of the GWSM4C yielded better prediction accuracy for significant wave height in global swell pools. The root mean square errors in the West African and East Pacific regions reduced from approximately 0.3 m, in the original model to about 0.15 m, in the new model. Moreover, these improvements were attributed to the higher efficiency of the newly modified neural network structure that allows the inclusion of more historical winds while maintaining acceptable computational consumption.

Abstract With the International Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E17 guidelines in effect from 2018, the design of Asia‐inclusive multiregional clinical trials (MRCTs) has been streamlined, thereby enabling efficient simultaneous global development. Furthermore, with the recent regulatory reforms in China and its drug administration joining the ICH as a full regulatory member, early participation of China in the global clinical development of novel investigational drugs is now feasible. This would also allow for inclusion of the region in the geographic footprint of pivotal MRCTs leveraging principles of the ICH E5 and E17. Herein, we describe recent case examples of model‐informed Asia‐inclusive global clinical development in the EMD Serono portfolio, as applied to the ataxia telangiectasia and Rad3‐related inhibitors, tuvusertib and berzosertib (oncology), the toll‐like receptor 7/8 antagonist, enpatoran (autoimmune diseases), the mesenchymal–epithelial transition factor inhibitor tepotinib (oncology), and the antimetabolite cladribine (neuroimmunological disease). Through these case studies, we illustrate pragmatic approaches to ethnic sensitivity assessments and the application of a model‐informed drug development toolkit including population pharmacokinetic/pharmacodynamic modeling and pharmacometric disease progression modeling and simulation to enable early conduct of Asia‐inclusive MRCTs. These examples demonstrate the value of a Totality of Evidence approach where every patient's data matter for de‐risking ethnic sensitivity to inter‐population variations in drug‐ and disease‐related intrinsic and extrinsic factors, enabling inclusive global development strategies and timely evidence generation for characterizing benefit/risk of the proposed dosage in Asian populations.

ObjectiveThe aim of this investigation is to explore the efficacy of combined exercise in elderly patients with hypertension. Moreover, we aim to delve into the underlying mechanisms governing blood pressure regulation, with the objective of promoting the adoption of this exercise regimen among elderly hypertensive individuals.MethodsIn our study, we conducted a thorough search across multiple databases, including PubMed, Web of Science, Cochrane Library, Embase, and Scopus. This extensive search resulted in the preliminary screening of 2,347 articles. Among these, 9 studies were carefully selected for an in-depth analysis. For our meta-analysis, we employed Review Manager 5.3 and Stata 15.0, enabling us to perform detailed subgroup analyses and assess the possibility of publication bias.ResultsIn comparison to the control group (n = 194), individuals enrolled in the combined exercise group (n = 200) exhibited a notable decrease in both resting systolic blood pressure (SBP) [weighted mean difference (WMD) = −11.17 mm Hg, 95% confidence interval (CI) (−17.13, −5.22), Z = 3.68, P

Abstract To enhance the anesthetic efficacy and reduce toxic side effects, a strategy is proposed involving the utilization of general anesthetics of Propofol (Pro) and Etomidate (Eto) to synergistic inhibition GABA receptors simultaneously. Four‐in‐one molecular aggregates were prepared to implement this strategy, which comprised of Pro and Eto with the bridging molecule monoglyceride monooleate (GMO) and surfactant F127 through intermolecular forces. The blood‐brain barrier (BBB) targeted lactoferrin (LF) is affixed to their surface, obtaining the final molecular aggregates. By employing lactoferrin enrich aggregates to the BBB, followed by ultrasound combine microbubbles to open the BBB, a remarkable 4.5‐fold enhancement in brain drug delivery was achieved. The molecular aggregates group maintained stable parameters of heart rate, diastolic blood pressure, and systolic blood pressure. A notable increase of more than twice therapeutic index (TI) value was observed, implying their higher anesthesia efficiency and reduced toxicity. Electroencephalogram (EEG) experiments demonstrate a significant elevation in the proportion of δ waves from 28% to 80% for aggregates, accompanied by a nearly fivefold reduction in the proportion of θ waves, meaning a significant improvement in synergistic anesthesia effectiveness (interaction index 0.289) with lower drug dosage. Furthermore, mouse immunofluorescence brain slice experiments suggest Pro and Eto enter the GABA receptor simultaneously, resulting in synergistic inhibition of GABA receptors.

Abstract BackgroundVideo-based error correction (VBEC) in medical education could offer immediate feedback, promote enhanced learning retention, and foster reflective practice. However, its application in cardiopulmonary resuscitation (CPR) training has not been investigated. ObjectiveThe objective of this study is to assess whether the VBEC procedure could improve the training performance of CPR among anesthesiology residents. MethodsA quasi-experimental study was conducted among anesthesiology residents between December 2022 and April 2023. Primary outcomes included a posttraining knowledge test and practical assessment scores. Secondary outcomes included the number of residents who correctly conducted CPR at each step, the rate of common mistakes during the CPR process, and the self-assessment results. A total of 80 anesthesiology residents were divided into a VBEC group (n=40) and a control group (n=40). The VBEC group underwent a 15-minute VBEC CPR training, whereas the control group underwent a 15-minute video-prompting CPR training. ResultsThe posttraining knowledge test score of the VBEC group was significantly higher than that of the control group (73, SD 10.5 vs 65.1, SD 11.4; PPPPP ConclusionsVBEC may be a promising strategy compared to video prompting for CPR training among anesthesiology residents.

Summary: Lavender essential oil (LEO) has been shown to relieve pain in humans, but the underlying neural mechanisms remain unknown. Here, we found that inhalation exposure to 0.1% LEO confers antinociceptive effects in mice with complete Freund adjuvant (CFA)-induced inflammatory pain through activation of projections from the anterior piriform cortex (aPir) to the insular cortex (IC). Specifically, in vivo fiber photometry recordings and viral tracing data show that glutamatergic projections from the aPir (aPirGlu) innervate GABAergic neurons in the IC (ICGABA) to inhibit local glutamatergic neurons (ICGlu) that are hyperactivated in inflammatory pain. Optogenetic or chemogenetic activation of this aPirGlu→ICGABA→Glu pathway can recapitulate the antinociceptive effects of LEO inhalation in CFA mice. Conversely, artificial inhibition of IC-projecting aPirGlu neurons abolishes LEO-induced antinociception. Our study thus depicts an LEO-responsive olfactory system circuit mechanism for alleviating inflammatory pain via aPir→IC neural connections, providing evidence to support development of aroma-based treatments for alleviating pain.

Giant cell glioblastoma often exhibits genome instability and is frequently associated with mutations in genes involved in DNA repair pathways including TP53 and DNA mismatch repair genes. Several germline mutations have been identified in giant cell glioblastoma, including mutations of MSH1 and MSH2, TP53, and POLE. We have documented a case of a germline mutation in CHEK2, another gene crucial to DNA repair, in a patient with giant cell glioblastoma. The CHEK2 mutation was inherited from the patient’s father, who had a history of gastric cancer and renal cell carcinoma. In addition to the germline CHEK2 mutation, the giant cell glioblastoma exhibited a genome-wide loss of heterozygosity, a characteristic observed in a subset of giant cell glioblastomas. Additional mutations detected in the tumor included TP53, PTEN, and a PTPRZ1-MET fusion. This represents the first reported case of a CHEK2 germline mutation in giant cell glioblastoma, further supporting the significance of impaired DNA repair mechanisms in the development of this disease.

Background: Few studies have compared the performances of those reported miRNAs as biomarkers for heart failure with reduced EF (HFrEF) in a population at high risk. The purpose of this study is to investigate comprehensively the performance of those miRNAs as biomarkers for HFrEF. Methods: By using bioinformatics methods, we also examined these miRNAs' target genes and possible signal transduction pathways. We collected serum samples from patients with HFrEF at Zhongshan Hospital. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of those miRNAs as biomarkers for HFrEF. miRWALK2.0, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to predict the target genes and pathways of selected miRNAs. Results: The study included 48 participants, of whom 30 had HFrEF and 18 had hypertension with normal left ventricular ejection fraction (LVEF). MiR-378, miR-195-5p were significantly decreased meanwhile ten miRNAs were remarkably elevated (miR-21-3p, miR-21-5p, miR-106-5p, miR-23a-3p, miR-208a-3p, miR-1-3p, miR-126-5p, miR-133a-3p, miR-133b, miR-223-3p) in the serum of the HFrEF group. Conclusion: The combination of miR 133a-3p, miR 378, miR 1-3p, miR 106b-5p, and miR 133b has excellent diagnostic performance for HFrEF, and there is a throng of mechanisms and pathways by which regulation of these miRNAs may affect the risk of HFrEF.

Analyzing capacity degradation characteristics and accurately predicting the knee point of capacity are crucial for the safety management of lithium-ion batteries (LIBs). However, the degradation mechanism of LIBs is complex. A key but challenging problem is how to clarify the degradation mechanism and predict the knee point. According to the external characteristics such as capacity decline gradievnt and the peak value of increment capacity curve (IC curve), the capacity degradation can be divided into four stages, including initial decline stage, slow decline stage, transition stage and high-speed decline stage. The degradation mechanism of LIBs is compared from the longitudinal and horizontal aspects, respectively. Among them, the battery usage from the initial stage to the end of life (EOL) is longitudinal analysis. The battery under different conditions, such as charging and discharging, different discharge rate, different cathode material degradation mechanism is horizontal analysis. Moreover, a method based on neural network is proposed to predict the knee point. Two features are used to predict the capacity and cycle of the knee point, which are the gradient of the capacity degradation curve and the difference of the IC curve with the maximum correlation. The experimental results show that a two-dimensional surface can be obtained using only the first 100 cycles, which can provide a reference for the position of the knee point accurately prediction.

Background: Calcitriol (Cal) is the most active metabolite of vitamin D and has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the role of Cal in noise-induced hearing loss (NIHL) to further elucidate the mechanism of noise-induced oxidative stress in the mouse cochlea. Methods: C57BL/6 J mice were given six intraperitoneal injections of Cal (500 ng/kg/d). After 14 days of noise exposure, auditory brainstem response (ABR) thresholds, and the cochlear outer hair cell loss rate were analysed to evaluate auditory function. Real-time fluorescence quantitative PCR, immunofluorescence and western blotting were performed in vitro after the treatment of cochlear explants with 100 µM tert-butyl hydroperoxide (TBHP) for 2.5 h and HEI-OC1 cells with 250 µM TBHP for 1.5 h. Results: In vivo experiments confirmed that Cal pretreatment mitigated NIHL and outer hair cell death. The in vitro results demonstrated that Cal significantly reduced TBHP-induced cochlear auditory nerve fibre degradation and spiral ganglion neuron damage. Moreover, treatment with Cal inhibited the expression of oxidative stress-related factors (3-NT and 4-HNE) and DNA damage-related factors (γ-H2A.X) and attenuated TBHP-induced apoptosis in cochlear explants and HEI-OC1 cells. A total of 1479 upregulated genes and 1443 downregulated genes were screened in cochlear tissue 1 h after noise exposure. The level of transcription factor 3 (ATF3) was significantly elevated in HEI-OC1 cells after TBHP stimulation. Gene Transcription Regulation Database （GTRD）and Cistrome database analyses revealed that the downstream target gene of ATF3 is dual specificity phosphatase 1 (DUSP1). Cistrome DB Toolkit database results showed that the transcription factor of DUSP1 was ATF3. In addition, the ChIP-PCR results indicated that ATF3 might be a direct transcription factor of DUSP1. Conclusion: The results of our study suggest that Cal attenuates NIHL and inhibits noise-induced apoptosis by regulating the ATF3/DUSP1 signalling pathway.

The protection dead-zone and threshold setting difficulties of the residual current devices (RCDs) in low-voltage distribution networks may lead to the misidentification of electric shock fault, resulting in severe life-threatening accidents. This paper proposes an electric shock fault identification method based on artificial intelligence for RCDs. Firstly, Mallat discrete wavelet transform (DWT) is applied to efficiently extract non-stationary electric shock feature signals from the total residual current with various noises, preventing weak non-stationary electric shock feature signals from being filtered out. Based on the average and maximum components of the signal mutation, an adaptive threshold can be determined to detect electric shock accurately, avoiding the false activation of RCDs caused by load fluctuations. Subsequently, an autoencoder (AE) is built to mine the non-linear features in which the signal of electric shock on living gradually rises and the signal of electric shock on non-living remains stable. Finally, a back propagation neural network (BPNN) is trained to classify the electric shock types from the non-linear features. The simulation and experiment have been conducted to obtain total residual current data under different conditions, and the electric shock fault real-time identification hardware platforms are developed. The accuracy of electric shock fault detection and classification can reach 100 %, which has advanced its practical applicability.

Abstract Resistive switching memories have garnered significant attention due to their high‐density integration and rapid in‐memory computing beyond von Neumann's architecture. However, significant challenges are posed in practical applications with respect to their manufacturing process complexity, a leakage current of high resistance state (HRS), and the sneak‐path current problem that limits their scalability. Here, a mild‐temperature thermal oxidation technique for the fabrication of low‐power and ultra‐steep memristor based on Ag/TiOx/SnOx/SnSe2/Au architecture is developed. Benefiting from a self‐assembled oxidation layer and the formation/rupture of oxygen vacancy conductive filaments, the device exhibits an exceptional threshold switching behavior with high switch ratio exceeding 106, low threshold voltage of ≈1 V, long‐term retention of >104 s, an ultra‐small subthreshold swing of 2.5 mV decade−1 and high air‐stability surpassing 4 months. By decreasing temperature, the device undergoes a transition from unipolar volatile to bipolar nonvolatile characteristics, elucidating the role of oxygen vacancies migration on the resistive switching process. Further, the 1T1R structure is established between a memristor and a 2H‐MoTe2 transistor by the van der Waals (vdW) stacking approach, achieving the functionality of selector and multi‐value memory with lower power consumption. This work provides a mild‐thermal oxidation technology for the low‐cost production of high‐performance memristors toward future in‐memory computing applications.

Apportioning pollution sources under compound pollution conditions is challenging in river pollution source analysis. The positive matrix factorization (PMF) model is widely used to analyze river pollution sources. However, the identification of pollutants in this model relies primarily on the subjective experience of the researchers, leading to ineffective identification of different contaminants from similar sources. In this study, we propose a comprehensive deviation index (CDI) to quantitatively identify pollution source types based on the PMF and observed source profiles. Taking the subtropical Xizhijiang River Basin as a case study, we quantitatively identified the pollution sources and their contributions to dissolved organic carbon (DOC), total nitrogen (TN), and total phosphorus (TP) using observed water quality and pollution sources data. The results showed that the eight major pollutants in the study region exhibited significant positive correlations, indicating the similarity of pollutant sources in the watershed. The PMF model identified three primary pollution sources with coefficients of determination for observed versus predicted concentrations ranging from 0.60 to 0.98. The CDI unveiled that the watershed's three pollution sources were farmland, rural, and wastewater treatment plants (WTPs). Farmland emerges as the predominant contributor to DOC (68.04 %), TC (63.29 %), and TDP (44.51 %). Rural notably contributes to NH3-N, PO43−, TDP, and TN, with percentages of 86.37 %, 57.65 %, 41.40 %, and 30.45 %, respectively. WTPs significantly contribute to NO2−, NO3−, and TN, accounting for 71.81 %, 57.39 %, and 37.26 %, respectively. Incorporating source fingerprints into the PMF model, the CDI can accurately identify pollution sources, improve the interpretability of source identification, and mitigate uncertainty in the multiple-source unknown receptor model. These findings have immediate and practical implications for river ecosystem management and pollution control, providing a more effective method for identifying and addressing pollution sources.

Mariculture ponds are essential components of the coastal wetland, which are often criticized by eutrophication risk for the dissolved inorganic nitrogen (DIN) input to the coastal zone by the culture tailwater. However, the reduce of this DIN pollution was difficult because the tailwater is hard to collect and the treatment is inefficient and expensive. Sesuvium Portulacastrum is a coastal vegetation which has high efficiency in DIN absorption from the seawater and sediment. In this study, we use Sesuvium Portulacastrum as a tool species to study the control behavior of the DIN in mariculture ponds wetland. The change trend of DIN in pond water and benthic species in pond sediment was investigated. The results showed that Sesuvium Portulacastrum reduced NH4+, NO3-, and NO2- in the pond water by 83.21%, 95.22%, and 91.32%, respectively. The species number of benthic organisms was enhanced from 2 to 5 and the species structure was more optimized in Sesuvium Portulacastrum pond than control pond. At the end of the experiment, eutrophication indicator species (Capitella capitata) was disappeared in the Sesuvium Portulacastrum pond. Those suggest that the coastal vegetation (Sesuvium Portulacastrum) have great potential to eliminate DIN pollutants in mariculture pond wetland.

Abstract In the past, hydrogen sulfide (H2S) was recognized as a toxic and dangerous gas; in recent years, with increased research, we have discovered that H2S can act as an endogenous regulatory transmitter. In mammals, H2S‐catalyzing enzymes, such as cystathionine‐β‐synthase, cystathionine‐γ‐lyase, and 3‐mercaptopyruvate sulfurtransferase, are differentially expressed in a variety of tissues and affect a variety of biological functions, such as transcriptional and posttranslational modification of genes, activation of signaling pathways in the cell, and metabolic processes in tissues, by producing H2S. Various preclinical studies have shown that H2S affects physiological and pathological processes in the body. However, a detailed systematic summary of these roles in health and disease is lacking. Therefore, this review provides a thorough overview of the physiological roles of H2S in different systems and the diseases associated with disorders of H2S metabolism, such as ischemia–reperfusion injury, hypertension, neurodegenerative diseases, inflammatory bowel disease, and cancer. Meanwhile, this paper also introduces H2S donors and novel release modes, as well as the latest preclinical experimental results, aiming to provide researchers with new ideas to discover new diagnostic targets and therapeutic options.

BackgroundRestricting salt, caffeine, and alcohol intake is commonly recommended as a first-line treatment for patients with Ménière’s disease (MD). However, it remains unclear whether these interventions effectively improve symptoms of MD. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the relationship between these dietary modifications and MD.MethodsSummary statistics for salt added to food, alcohol consumption, coffee consumption, and MD were sourced from the United Kingdom Biobank, GSCAN, and the FinnGen study, involving up to 941,280 participants. The main analyses were performed using the random-effects inverse-variance weighted (IVW) approach and were complemented by four additional methods. Multiple sensitivity analyses were performed to validate the findings, and both forward and reverse MR analyses were employed to address potential reverse causality bias.ResultsThe primary MR results using the IVW method revealed that salt added to food (OR = 0.719, 95% CI: 0.429–1.206; p = 0.211), alcohol consumption (OR = 0.834, 95% CI: 0.427–1.628; p = 0.595), and coffee consumption (OR = 0.852, 95% CI: 0.555–1.306; p = 0.461) were not significantly correlated with MD. In reverse analysis, no evidence of significant effect was found from MD to salt added to food (OR = 1.000, 95% CI: 0.993–1.007; p = 0.957), alcohol consumption (OR = 0.998, 95% CI: 0.987–1.008; p = 0.682), and coffee consumption (OR = 0.998, 95% CI: 0.985–1.011; p = 0.72).ConclusionThis MR analysis did not identify convincing evidence to support the idea that restricting salt, caffeine, and alcohol intake is beneficial for the treatment of MD.

IntroductionThus far, the impact of kaolin mining activities on the surrounding native plants and rhizosphere microecology has not been fully understood.MethodsIn this study, we used 16S rRNA high-throughput sequencing to examine the impact of kaolin mining on the rhizosphere bacterial communities and functions of three local plant species: Conyza bonariensis, Artemisia annua, and Dodonaea viscosa.ResultsThe results showed that kaolin mining significantly reduced the diversity of rhizosphere bacteria in these plants, as indicated by the Shannon, Simpson, Chao1, and observed species indices (p

TTFields is a novel FDA-approved technology utilized for treating glioblastoma multiforme (GBM) within the brain. Presently, the effectiveness of therapy is evaluated through MRI imaging at random two-month intervals. Electrical impedance is an important and effective parameter for reflecting changes in tissue properties. In TTFields treatment for brain tumors, electrodes attached to the scalp deliver electric field energy to the tumor region. We hypothesize that these electrodes can also serve as sensors to detect impedance changes caused by tumor alterations in real time, thus continuously assessing the effectiveness of the treatment. In this work, we propose and scrutinize this hypothesis by conducting an in silico study to confirm the potential feasibility of the proposed concept. Our results indicate that the impedance amplitude change measured between opposing TTFields electrode arrays utilizing voltage and frequency of 50 V and 200 kHz (typical TTFields treatment parameters), has enough resolution (> 1mm) and Signal-to-Noise Ratio (> 40 dB) to evaluate tumor size change in the head. The impedance detection technique may be a significant augmentation to TTFields cancer treatment, enabling the continuous evaluation of safety and efficacy throughout the procedure.

ObjectivePreoperative diagnosis for follicular thyroid cancer (FTC) remains challenging. The purpose of this study was to explore the maximum intensity projection (MIP) features, which can be utilized for reconstructing and characterizing the structure of microvascular in tissue, associated with FTC, and to explore the independent risk factors for FTC in combination with multimodal ultrasonography and blood indicators.MethodsThis single-center, prospective, single-blind, observational study included patients with suspected follicular thyroid carcinoma based on preoperative ultrasonography findings. All patients underwent routine ultrasonography, contrast-enhanced ultrasonography (CEUS), and correlated blood indexes tests. Offline MIP reconstruction of the CEUS images was performed. The tumor was histologically diagnosed postoperatively. Multivariable logistics regression was utilized for analyzing MIP characteristics combined with multimodal ultrasonography and preoperative blood indicators to identify independent risk factors for FTC.ResultsIn this study, 61 thyroid nodules were finally included according to the atretic criteria. (1) Compared with traditional color profile ultrasonography and CEUS, MIP technology can provide more information regarding microvascular characteristics inside thyroid tumors. The short, rod-like, crossed, curved and firework-like features of MIP images revealed statistically significant differences between the benign and malignant groups. (2) Multivariable logistic regression analysis indicated that the firework-like MIP characteristics of microvascular, thyroglobulin (Tg) level and vessel intensity (VI) value were independent risk factors for malignancy.Conclusion(1) MIP technology has potential applications in the differential diagnosis of follicular thyroid carcinoma from benign lesions. (2) Firework MIP microvascular characteristics, Tg values and VI values can serve as parameters for the differential diagnosis of follicular thyroid carcinoma from benign lesions. This study provides a novel approach idea for preoperative multimodal differentiation of follicular thyroid carcinoma from benign lesions.

Abstract Background Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common acute respiratory failure due to diffuse pulmonary inflammation and oedema. Elaborate regulation of macrophage activation is essential for managing this inflammatory process and maintaining tissue homeostasis. In the past decades, metabolic reprogramming of macrophages has emerged as a predominant role in modulating their biology and function. Here, we observed reduced expression of carnitine palmitoyltransferase 1A (CPT1A), a key rate‐limiting enzyme of fatty acid oxidation (FAO), in macrophages of lipopolysaccharide (LPS)‐induced ALI mouse model. We assume that CPT1A and its regulated FAO is involved in the regulation of macrophage polarization, which could be positive regulated by interleukin‐10 (IL‐10). Methods After nasal inhalation rIL‐10 and/or LPS, wild type (WT), IL‐10‐/‐, Cre‐CPT1Afl/fl and Cre+CPT1Afl/fl mice were sacrificed to harvest bronchoalveolar lavage fluid, blood serum and lungs to examine cell infiltration, cytokine production, lung injury severity and IHC. Bone marrow‐derived macrophages (BMDMs) were extracted from mice and stimulated by exogenous rIL‐10 and/or LPS. The qRT‐PCR, Seahorse XFe96 and FAO metabolite related kits were used to test the glycolysis and FAO level in BMDMs. Immunoblotting assay, confocal microscopy and fluorescence microplate were used to test macrophage polarization as well as mitochondrial structure and function damage. Results In in vivo experiments, we found that mice lacking CPT1A or IL‐10 produced an aggravate inflammatory response to LPS stimulation. However, the addition of rIL‐10 could alleviate the pulmonary inflammation in mice effectively. IHC results showed that IL‐10 expression in lung macrophage decreased dramatically in Cre+CPT1Afl/fl mice. The in vitro experiments showed Cre+CPT1Afl/fl and IL‐10‐/‐ BMDMs became more “glycolytic”, but less “FAO” when subjected to external attacks. However, the supplementation of rIL‐10 into macrophages showed reverse effect. CPT1A and IL‐10 can drive the polarization of BMDM from M1 phenotype to M2 phenotype, and CPT1A‐IL‐10 axis is also involved in the process of maintaining mitochondrial homeostasis. Conclusions CPT1A modulated metabolic reprogramming and polarisation of macrophage under LPS stimulation. The protective effects of CPT1A may be partly attributed to the induction of IL‐10/IL‐10 receptor expression.

Abstract Background and main body Although interactions between the nervous and immune systems have been recognized decades ago, it has become increasingly appreciated that neuroimmune crosstalk is among the driving factors of multiple pulmonary inflammatory diseases including acute lung injury (ALI). Here, we review the current understanding of nerve innervations towards the lung and summarize how the neural regulation of immunity and inflammation participates in the onset and progression of several lung diseases, especially ALI. We then present advancements in the development of potential drugs for ALI targeting neuroimmune interactions, including cholinergic anti‐inflammatory pathway, sympathetic‐immune pathway, purinergic signalling, neuropeptides and renin‐angiotensin system at different stages from preclinical investigation to clinical trials, including the traditional Chinese medicine. Conclusion This review highlights the importance of considering the therapeutic strategy of inflammatory diseases within a conceptual framework that integrates classical inflammatory cascade and neuroimmune circuits, so as to deepen the understanding of immune modulation and develop more sophisticated approaches to treat lung diseases represented by ALI. Key points The lungs present abundant nerve innervations. Neuroimmune interactions exert a modulatory effect in the onset and progression of lung inflammatory diseases, especially acute lung injury. The advancements of potential drugs for ALI targeting neuroimmune crosstalk at different stages from preclinical investigation to clinical trials are elaborated. Point out the direction for the development of neuroimmune pharmacology in the future.

This review explores the evolving landscape of blood biomarkers in the diagnosis of tuberculosis (TB), focusing on biomarkers derived both from the pathogen and the host. These biomarkers provide critical insights that can improve diagnostic accuracy and timeliness, essential for effective TB management. The document highlights recent advancements in molecular techniques that have enhanced the detection and characterization of specific biomarkers. It also discusses the integration of these biomarkers into clinical practice, emphasizing their potential to revolutionize TB diagnostics by enabling more precise detection and monitoring of the disease progression. Challenges such as variability in biomarker expression and the need for standardized validation processes are addressed to ensure reliability across different populations and settings. The review calls for further research to refine these biomarkers and fully harness their potential in the fight against TB, suggesting a multidisciplinary approach to overcome existing barriers and optimize diagnostic strategies. This comprehensive analysis underscores the significance of blood biomarkers as invaluable tools in the global effort to control and eliminate TB.

In this study, the effect of different acetylated distarch phosphate (ADSP) ratios (0, 1%, 2%, 3%, 4%, 5%) on the physicochemical characteristics and stability of the oyster sauce (OS) system was investigated. The texture, water state, interactions, rheological properties, microstructure, and stability of OS samples were analyzed through the texture analyser, low-field nuclear magnetic resonance (LF-NMR), particle diameter and zeta potential, fourier-transform infrared spectroscopy (FTIR), rheometer, and microscopes. The results revealed that the addition of ADSP improved the firmness, consistency, cohesiveness, and water-holding capacity of OS. Moreover, ADSP reduced the average particle size and zeta potential of OS, indicating that electrostatic and steric stabilization existed in the ADSP-OS system. The addition of ADSP enhanced the hydrogen bonding and decreased water mobility for OS system, processing a more continuous and smooth structure. All ADSP-OS samples were typical non-Newtonian fluids with shear-thinning characteristics. In addition, the non-significant instability index changes of ADSP-OS over the whole storage period confirmed the excellent long-term stabilization capability of OS prepared with ADSP. This study provides a theoretical basis for starch-based sauce products and contributes to the development of sauce products.

The western Pacific seamount area is abundant in both biological and mineral resources, making it a crucial location for international investigation of regional seabed resources. An essential stage in comprehending and advancing seamounts is gaining knowledge about the distribution characteristics and laws governing the seabed substrate. Deep-sea geological sampling is challenging because of the intricate nature of the deep-sea environment, resulting in increased difficulty in identifying and evaluating substrates. This study addresses the aforementioned issues by utilizing in-situ video footage obtained from the “Jiaolong” manned deep submersible and shipborne deep-water multibeam data. This data is used as a foundation for constructing a Western Pacific seamount areas substrate classification point set. Additionally, the paper introduces the mRMR-XGBoost substrate classification model. Substrate categorization in deep sea and mountainous regions has been successfully accomplished, yielding a classification accuracy of 92.5%. The classification experiments and box sampling results demonstrate that the mRMR-XGBoost substrate classification model proposed in this paper can efficiently use acoustic and optical data to accurately divide the substrate types in seamount areas, with better classification accuracy, when compared with commonly used machine learning models. It has a significant application value and the best classification effect on the two types of substrates: nodules and gravel substrates.

Guizhou Province has many multi-layer, thin-thick coal seams; however, complex geology, incomplete reservoir characterization, and sweet-spot selection technology prevent large-scale coalbed methane (CBM) development. This study evaluates the CBM reservoir properties within the Dahebian block using logging data, coal sample analysis, and well-testing data and develops a 3D static reservoir properties model to analyze their spatial and vertical propagation. A sweet spot evaluation model was established using a multi-level fuzzy method based on 9 parameters extracted from a 3D static reservoir properties model. The coal measure has 22 coal seams, and seams >2 m thick have 2 or 3 thin non-coal layers intercalated. Coal seams 1#, 7#, and 11# are thin to thick, deeply buried, widely distributed, and have high gas content and saturation. Undeformed and cataclastic coal predominates the coal seam 1# and 7#, whereas coal seam 11# is dominated by cataclastic and granulated coal. The southern and central parts of coal seam 7# and 11# have less tectonically deformed coal (TDC). Coal seams 1# and 7# have low permeability relative to seam 11# and are localized, while coal seams 11# have high permeability, are extensively distributed, and contain substantial gas concentrations. Comparative analysis of evaluation scores and CBM production statistics shows that high scores indicate sweet spots for CBM development. Sweet-spot potential was classified as high, medium, and low. Scattered sweet spots are found in single layers, while combined development (1# + 7#+11#) reveals a wider high-potential area in the south-central region. This area, featuring deep, thick coal seams, high permeability, gas saturation, reservoir pressure, and low TDC proportion, indicates significant development potential. This study validates CBM development statistics, identifies future development areas, and guides the development of geologically complex Guizhou CBM.

Summary: Facial infiltrating lipomatosis (FIL) is a congenital disorder. The pathogenesis of FIL is associated with PIK3CA mutations, but the underlying mechanisms remain undetermined. We found that the adipose tissue in FIL demonstrated adipocytes hypertrophy and increased lipid accumulation. All adipose-derived mesenchymal stem cells from FIL (FIL-ADSCs) harbored PIK3CA mutations. Moreover, FIL-ADSCs exhibited a greater capacity for adipogenesis. Knockdown of PIK3CA resulted in a reduction in the adipogenic potential of FIL-ADSCs. Furthermore, WX390, a dual-target PI3K/mTOR inhibitor, was found to impede PIK3CA-mediated adipogenesis both in vivo and in vitro. RNA sequencing (RNA-seq) revealed that the expression of transient receptor potential vanilloid subtype 1 (TRPV1) was upregulated after PI3K pathway inhibition, and overexpression or activation of TRPV1 both inhibited adipogenesis. Our study showed that PIK3CA mutations promoted adipogenesis in FIL-ADSCs and this effect was achieved by suppressing TPRV1. Pathogenesis experiments suggested that WX390 may serve as an agent for the treatment of FIL.

The incidence of ulcerative colitis (UC) is increasing each year, and its course is characterized by alternating remission-relapse; currently, there is no effective treatment for UC. Peptides produced from the hydrolysis of walnut proteins have physiological functions such as anti-inflammatory and antioxidant properties. The aim of this study was to analyze the preventive effect of walnut polypeptide (WP) on UC and to preliminarily screen bioactive peptides in WP. The results of in vitro experiments showed that WP was able to alleviate the LPS-induced inflammatory response by inhibiting M1 polarization in Raw 264.7 cells and thereby alleviating the LPS-induced inflammatory response. The results of in vivo experiments showed that dietary supplementation with 500 mg/kg WP significantly alleviated dextran sodium sulfate (DSS)-induced weight loss, colon shortening, and elevated DAI scores. WP treatment was able to suppress DSS-induced inflammatory responses in mice by inhibiting macrophage M1 polarization and NF-κB signaling pathway. WP intervention also helped maintain intestinal barrier integrity by promoting tight junction protein expression and mucus secretion. In addition, 16S rDNA sequencing showed that WP ameliorated gut microbial disorder induced by DSS, as evidenced by a decrease in the abundance of harmful bacteria (Erysipelatoclostridium, Helicobacter, and Parasutterella) and an increase in the abundance of beneficial bacteria (Flavonifractor, Anaerotignum, and Alistipes) after WP intervention. In conclusion, this study demonstrates that WP ameliorates DSS-induced colonic inflammation in mice by inhibiting inflammation, modulating the gut microbiota and repairing the intestinal barrier.

The water footprint (WF) is an essential indicator for assessing the pressure of human activities on freshwater resource utilization. The traditional WF model assumes that human water resource occupation comprises a green, blue, and grey WF, which can be linearly summed to the total WF. However, since there are two kinds of human demand for water resources, consumptive occupation and functional occupation, the relationship between them is not exclusive and does not have simple linear addition characteristics. The overlapping relationship between blue and grey WF has long been overlooked in the traditional WF calculation, resulting in a duplicate calculation of water requirement and exaggerating actual water resource demand. This study introduced a new index of blue-grey WF that deducted the overlapping portions of blue and grey WF, thereby calculating a region’s actual freshwater resource utilization. Northern Anhui, an arid region short of water resources with water pollution, was selected as a case study. The traditional WF calculation showed that the multi-year average WF of Northern Anhui was 3.44 × 1010 m3 from 2011 to 2020, with the grey, green, and blue WF accounting for 52.59 %, 27.63 %, and 19.78 %, respectively. The blue and grey WF overlapped each other and the blue WF can be fully covered by grey WF, resulting in a total blue-grey WF of 1.81 × 1010 m3, much lower than the sum of blue and grey WF. Based on the revised WF calculation model, the multi-year average WF of Northern Anhui was 2.76 × 1010 m3, decreased by 19.78 %, indicating a severe issue of duplicate calculation of blue and grey WF. The revised WF model could avoid the repeated calculation issues of water resources used by different functions. It provides a more reliable and accurate research method for regional water resources accounting and management decision-making.

Magnesium potassium phosphate cement (MKPC) and magnesium ammonium phosphate cement (MAPC) perform well as rapid repair materials, but the properties of their hydration products under NaCl attack (e.g., de-icing salt) are unknown. In this study, the synthesised magnesium phosphate cement (MPC) hydration products struvite and struvite-K were immersed in 5% and 15% NaCl solutions to study their phase and microstructural evolution. The results show that struvite partially dissolves in the pure water and NaCl solutions, without forming new crystalline hydrated products. However, in NaCl solutions, the morphology changes from scattered flakes to columnar structures. Struvite-K transforms into cattiite and hazenite (with higher strength) in the pure water and NaCl solutions, respectively, exhibiting flake-like morphology in pure water and clustered bloom morphology in NaCl solutions. The emergence of hazenite may contribute to MKPC displaying stronger resistance to NaCl corrosion compared to MAPC.

To address the low accuracy and stability when applying classical control theory in distribution networks with distributed generation, a control method involving flexible multistate switches (FMSs) is proposed in this study. This approach is based on an improved double-loop recursive fuzzy neural network (DRFNN) sliding mode, which is intended to stably achieve multiterminal power interaction and adaptive arc suppression for single-phase ground faults. First, an improved DRFNN sliding mode control (SMC) method is proposed to overcome the chattering and transient overshoot inherent in the classical SMC and reduce the reliance on a precise mathematical model of the control system. To improve the robustness of the system, an adaptive parameter-adjustment strategy for the DRFNN is designed, where its dynamic mapping capabilities are leveraged to improve the transient compensation control. Additionally, a quasi-continuous second- order sliding mode controller with a calculus-driven sliding mode surface is developed to improve the current monitoring accuracy and enhance the system stability. The stability of the proposed method and the convergence of the network parameters are verified using the Lyapunov theorem. A simulation model of the three-port FMS with its control system is constructed in MATLAB/Simulink. The simulation result confirms the feasibility and effectiveness of the proposed control strategy based on a comparative analysis.

Abstract Background Class III peroxidases (PODs) perform crucial functions in various developmental processes and responses to biotic and abiotic stresses. However, their roles in wheat seed dormancy (SD) and germination remain elusive. Results Here, we identified a wheat class III POD gene, named TaPer12-3A, based on transcriptome data and expression analysis. TaPer12-3A showed decreasing and increasing expression trends with SD acquisition and release, respectively. It was highly expressed in wheat seeds and localized in the endoplasmic reticulum and cytoplasm. Germination tests were performed using the transgenic Arabidopsis and rice lines as well as wheat mutant mutagenized with ethyl methane sulfonate (EMS) in Jing 411 (J411) background. These results indicated that TaPer12-3A negatively regulated SD and positively mediated germination. Further studies showed that TaPer12-3A maintained H2O2 homeostasis by scavenging excess H2O2 and participated in the biosynthesis and catabolism pathways of gibberellic acid and abscisic acid to regulate SD and germination. Conclusion These findings not only provide new insights for future functional analysis of TaPer12-3A in regulating wheat SD and germination but also provide a target gene for breeding wheat varieties with high pre-harvest sprouting resistance by gene editing technology.

Abstract Multi-modal combination therapy is regarded as a promising approach to cancer treatment. Combining chemotherapy and phototherapy is an essential multi-modal combination therapy endeavor. Ivermectin (IVM) is a potent antiparasitic agent identified as having potential antitumor properties. However, the fact that it induces protective autophagy while killing tumor cells poses a challenge to its further application. IR780 iodide (IR780) is a near-infrared (NIR) dye with outstanding photothermal therapy (PTT) and photodynamic therapy (PDT) effects. However, the hydrophobicity, instability, and low tumor uptake of IR780 limit its clinical applications. Here, we have structurally modified IR780 with hydroxychloroquine, an autophagy inhibitor, to synthesize a novel compound H780. H780 and IVM can form H780-IVM nanoparticles (H-I NPs) via self-assembly. Using hyaluronic acid (HA) to modify the H-I NPs, a novel nano-delivery system HA/H780-IVM nanoparticles (HA/H-I NPs) was synthesized for chemotherapy-phototherapy of colorectal cancer (CRC). Under NIR laser irradiation, HA/H-I NPs effectively overcame the limitations of IR780 and IVM and exhibited potent cytotoxicity. In vitro and in vivo experiment results showed that HA/H-I NPs exhibited excellent anti-CRC effects. Therefore, our study provides a novel strategy for CRC treatment that could enhance chemo-phototherapy by modulating autophagy.

Objective: This systematic review was conducted to evaluate the efficacy and safety of continuous nursing care for the recovery of joint function in older adults with total hip or knee arthroplasty. Methods: Randomized controlled trials and cohort studies of continuous nursing in older patients after joint replacement were searched from the database of Cochrane Library, Web of Science, PubMed, and Embase from their establishment to October 25, 2023. After literature screening, two researchers completed data extraction, and the risk of bias was assessed using the Cochrane risk-of-bias tool. The risk analysis included in cohort studies was based on the Newcastle-Ottawa Scale (NOS). Results: The study included a total of 15 articles, comprising 34,186 knee and hip replacement patients. In this review, the effects of continuous nursing on the recovery of joint function of knee replacement and hip replacement in older adults were classified and discussed. Continuous nursing interventions targeted for total hip replacement could greatly increase the range of joint mobility, enhance muscle strength during hip movements like flexion, extension, and abduction, maintain joint stability, relieve pain, improve daily activities, and lower the risk of complications. For older patients with knee arthroplasty, continuous nursing programs could markedly improve knee motion range, joint flexion, joint stability, daily activities, and pain management. Despite the implementation of interventions, the incidence of complications caused by total knee replacement did not decrease. Out of all the studies reviewed, only one used a theoretical framework for interventions provided to patients during the postoperative period of hip arthroplasty. The overall quality of the included studies was very high. Conclusion: Continuous nursing can effectively improve the joint function of older patients after joint replacement. However, its effectiveness in terms of clinical outcomes, patient satisfaction, and medical cost of associated continuous nursing needs to be further clarified. In addition, continuous nursing has no significant advantage in the safety of postoperative complications and readmission rates in older adults after knee joint replacement. To enhance the efficacy and safety of continuous nursing effectively, it is crucial to refine the continuous nursing program in the future, thereby elevating the quality of nursing services.

Aiming at the frost heave characteristics of long-distance and large-section underground freezing projects in cities, the double-line tunnel of Shanghai Metro Line 18 undercrossing an operation station was select as an example,a three-dimensional numerical model was established by using finite element software based on the thermal-mechanical coupling equation. Combined with the physical parameters obtained from laboratory tests, the evolution law of frost heave displacement field of the project was studied, and the influence of measures such as the staggered peak freezing and the adjustment of brine temperature on the frost heave displacement field was explored. Under the experimental conditions, the results show that: ① the deformation of the station floor caused by frost heave which mainly occurs in the active freezing period. When the double-line tunnel is frozen at the same time, the vertical displacement of the station floor at 45days of freezing reaches 77.72% of the displacement at 90 days of freezing. ② When the freezing time reaches 90 days, compared with simultaneous freezing, the displacement of the station floor reduced by 7.7% under the condtion of staggered peak freezing. The superposition effect of frost heave in the same time period is effectively avoided, and the frost heave effect is reduced to a certain extent. ③ When the freezing time reaches 90 days, compared with simultaneous freezing, the displacement of the station floor reduced by 34.2% under the condtion of adjusting the brine temperature, it shown that the expansion rate and frost heave effect of frozen soil are effectively controlled. In engineering practice, measures such as staggered freezing and adjusting brine temperature are used together to control frost heave, and the maximum vertical deformation of the station floor is 25.41 mm. The deformation law of the station floor obtained by numerical simulation is basically consistent with the measured data, which effectively guided the construction of the project.

Abstract For a long time, hydrogen sulfide (H2S) has been considered a toxic compound, but recent studies have found that H2S is the third gaseous signaling molecule which plays a vital role in physiological and pathological conditions. Currently, a large number of studies have shown that H2S mediates apoptosis through multiple signaling pathways to participate in cancer occurrence and development, for example, PI3K/Akt/mTOR and MAPK signaling pathways. Therefore, the regulation of the production and metabolism of H2S to mediate the apoptotic process of cancer cells may improve the effectiveness of cancer treatment. In this review, the role and mechanism of H2S in cancer cell apoptosis in mammals are summarized.

Abstract All-small-molecule organic solar cells with good batch-to-batch reproducibility combined with non-halogen solvent processing show great potential for commercialization. However, non-halogen solvent processing of all-small-molecule organic solar cells are rarely reported and its power conversion efficiencies are very difficult to improve. Herein, we designed and synthesized a small molecule donor BM-ClEH that can take advantage of strong aggregation property induced by intramolecular chlorine-sulfur non-covalent interaction to improve molecular pre-aggregation in tetrahydrofuran and corresponding micromorphology after film formation. Tetrahydrofuran-fabricated all-small-molecule organic solar cells based on BM-ClEH:BO-4Cl achieved high power conversion efficiencies of 15.0% in binary device and 16.1% in ternary device under thermal annealing treatment. In contrast, weakly aggregated BM-HEH without chlorine-sulfur non-covalent bond is almost inefficient under same processing conditions due to poor pre-aggregation induced disordered π-π stacking, indistinct phase separation and exciton dissociation. This work promotes the development of non-halogen solvent processing of all-small-molecule organic solar cells and provides further guidance.

Abstract Background Because of the progress on the diagnosis and treatment for patients with breast cancer (BC), the overall survival of the patients has been improved. However, a number of BC patients cannot benefit from the existing therapeutic strategies as the essential molecular events triggering the development of BC are not well understood. Previous studies have shown that abnormal expression of zinc finger proteins is involved in the development of various malignancies, whereas it remains largely unclear on their significance during the progression of BC. In this study, we aimed to explore the clinical relevance, cellular function and underlying mechanisms of zinc finger protein 468 (ZNF468) in BC. Methods The clinical relevance of ZNF468 and TFAM was analyzed based on TCGA database. Overexpression or knockdown of ZNF468 and TFAM were performed by transfecting the cells with overexpression plasmids and siRNAs, respectively. Overexpression and knockdown efficacy was checked by immunoblotting. CCK-8, colony formation, transwell and apoptosis experiments were conducted to check the cellular function of ZNF468 and TFAM. The content of mtDNA was measured by the indicated assay kit. The effects of cisplatin on BC cells were detected by CCK-8 and colony formation assays. The regulation of ZNF468 on TFAM was analyzed by RT-qPCR, immunoblotting, dual luciferase activity and ChIP-qPCR assays. Results ZNF468 was overexpressed in BC patients and inversely correlated with their prognosis. Based on overexpression and knockdown assays, we found that ectopic expression of ZNF468 was essential for the proliferation, growth and migration of BC cells. The expression of ZNF468 also negatively regulated the sensitivity of BC cells to the treatment of cisplatin. Mechanistically, ZNF468 potentiated the transcription activity of TFAM gene via direct binding on its promoter. Lastly, we demonstrated that ZNF468 up-regulation of TFAM was important for the growth, migration and cisplatin resistance in BC cells. Conclusion Our study indicates that ZNF468 promotes BC cell growth and migration via transcriptional activation of TFAM. ZNF468/TFAM axis can serve as the diagnostic and therapeutic target, as well as the predictor of cisplatin effectiveness in BC patients.

Abstract Background Patients with colorectal cancer (CRC) with liver metastasis or drug resistance have a poor prognosis. Previous research has demonstrated that PPP2R1B inactivation results in the development of CRC. However, the role of PPP2R1B in CRC metastasis and drug resistance is unclear. Methods Venny 2.1 was used to determine the intersection between survival-related differentially expressed genes (DEGs) and liver metastasis-related DEGs according to RNA-seq data from The Cancer Genome Atlas (TCGA) and the GEO database (GSE179979). LC‒MS/MS and coimmunoprecipitation were performed to predict and verify the substrate protein of PPP2R1B. Gene Set Variation Analysis (GSVA) was subsequently utilized to assess pathway enrichment levels. The predictive performance of PPP2R1B was assessed by regression analysis, Kaplan–Meier (KM) survival analysis and drug sensitivity analysis. Immunohistochemistry (IHC), qRT-PCR and western blotting were performed to measure the expression levels of related mRNAs or proteins. Biological features were evaluated by wound healing, cell migration and invasion assays and CCK-8 assays. A mouse spleen infection liver metastasis model was generated to confirm the role of PPP2R1B in the progression of liver metastasis in vivo. Results According to bioinformatics analysis, PPP2R1B is significantly associated with liver metastasis and survival in CRC patients, and these findings were further verified via immunohistochemistry (IHC), qPCR and Western blotting. Pathway enrichment and LC‒MS/MS analysis revealed that PPP2R1B is negatively associated with the MAPK/ERK signalling pathway. Additionally, PD98059, a MAPK/ERK pathway inhibitor, inhibited EMT in vitro by reversing the changes in key proteins involved in EMT signalling (ZEB1, E-cadherin and Snail) and ERK/MAPK signalling (p-ERK) mediated by PPP2R1B. Oxaliplatin sensitivity prediction and validation revealed that PPP2R1B silencing decreased Oxaliplatin chemosensitivity, and these effects were reversed by PD98059 treatment. Moreover, PPP2R1B was coimmunoprecipitated with p-ERK in vitro. A negative correlation between PPP2R1B and p-ERK expression was also observed in clinical CRC samples, and the low PPP2R1B/high p-ERK coexpression pattern indicated a poor prognosis in CRC patients. In vivo, PPP2R1B silencing significantly promoted liver metastasis. Conclusions This study revealed that PPP2R1B induces dephosphorylation of the p-ERK protein, inhibits liver metastasis and increases Oxaliplatin sensitivity in CRC patients and could be a potential candidate for therapeutic application in CRC.

Abstract Background Extensive metastatic and refractory cancer pain is common, and exhibits a dissatisfactory response to the conventional intrathecal infusion of opioid analgesics. Case Presentation The present study reports a case of an extensive metastatic esophageal cancer patient with severe intractable pain, who underwent translumbar subarachnoid puncture with intrathecal catheterization to the prepontine cistern. After continuous infusion of low-dose morphine, the pain was well-controlled with a decrease in the numeric rating scale (NRS) of pain score from 9 to 0, and the few adverse reactions to the treatment disappeared at a low dose of morphine. Conclusions The patient achieved a good quality of life during the one-month follow-up period.

Abstract Background The aim of this study was to identify the risk factors for postoperative delirium (POD) in elderly patients undergoing heart valve surgery with cardiopulmonary bypass (CPB). Methods Elderly patients undergoing elective heart valve surgery with CPB in The First Affiliated Hospital of Wenzhou Medical University between March 2022 and March 2023 were selected for this investigation. They were divided into a POD group and a non-POD group. Their baseline information was collected and recorded, and the patients were subjected to neurocognitive function assessment using the Mini-Mental State Examination and the Montreal Cognitive Assessment scales before surgery. We also recorded their intraoperative indicators such as duration of surgery, duration of CPB, duration of aortic cross-clamp, blood transfusion, and postoperative indicators such as duration of mechanical ventilation, postoperative 24-hour drainage volume, and pain score. Regional cerebral oxygen saturation was monitored intraoperatively by near-infrared spectroscopy based INVOS5100C Regional Oximeter. Patients were assessed for the occurrence of POD using Confusion Assessment Method for the Intensive Care Unit, and logistic regression analysis of risk factors for POD was performed. Results The study finally included 132 patients, with 47 patients in the POD group and 85 ones in the non-POD group. There were no significant differences in baseline information and preoperative indicators between the two groups. However, marked differences were identified in duration of surgery, duration of CPB, duration of aortic cross-clamp, duration of postoperative mechanical ventilation, postoperative length of stay in cardiac intensive care unit, postoperative length of hospital stay, intraoperative blood transfusion, postoperative pain score, and postoperative 24-hour drainage volume between the two groups (p 285 min (OR, 1.021 [95% CI, 1.008–1.035]; p = 0.002), duration of postoperative mechanical ventilation > 23.5 h (OR, 6.210 [95% CI, 1.619–23.815]; p = 0.008), and postoperative CCU stay > 3.5 d (OR, 3.927 [95% CI, 1.046–14.735]; p = 0.043) were independent risk factors of the occurrence of POD while change of rScO2 at T1>50.5 (OR, 0.832 [95% CI 0.736–0.941]; p = 0.003) was a protective factor for POD. Conclusion Duration of surgery duration of postoperative mechanical ventilation and postoperative CCU stay are risk factors for POD while change of rScO2 at T1 is a protective factor for POD in elderly patients undergoing heart valve surgery with CPB.

Abstract Background Facial infiltrating lipomatosis (FIL) is a rare condition characterized by congenital facial enlargement. Beyond its impact on physical appearance, FIL can also impair essential facial functions such as swallowing, chewing, vision, and breathing, imposing a substantial physiological and psychological burden. Currently, fewer than 80 cases of FIL have been reported, and the characteristics and management strategies for FIL remain unclear. Methods We reviewed the clinical, surgical, and radiological records of 39 FIL patients who were treated at our center. Of these, genetic testing was performed for 21 patients. Results Aberrant overgrowth involves subcutaneous fat, bones, muscles, glands, tongue, lips, and teeth. Epidermal nevi could be observed in the dermatomes innervated by the three branches of the trigeminal nerve, with the highest frequency seen in the dermatome of the mandibular branch. Four patients exhibited concurrent hemimegalencephaly (HMEG), with one case presenting HMEG on the opposite side of the FIL. Nineteen patients were confirmed to harbor the PIK3CA mutation. Thirty-three patients underwent surgical procedures, with a post resection recurrence rate of approximately 25%. Conclusions A variety of maxillofacial structures may be involved in FIL. PIK3CA mutations are important pathogenic factors. Emerging targeted therapies could present an additional treatment avenue in the future. However, surgery currently remains the predominant treatment choice for FIL. The timing and modality of surgery should be individually customized, taking into account each patient's unique circumstances. Notably, there is a significant possibility of postoperative recurrence during childhood and adolescence, necessitating early strategic planning of disease management.

Abstract. Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous system. Compared with patients with other cancers, glioma patients often suffer from increased levels of psychological stress, such as anxiety and fear. Chronic stress (CS) is thought to impact glioma profoundly. However, because of the complex mechanisms underlying CS and variability in individual tolerance, the role of CS in glioma remains unclear. This review suggests a new proposal to redivide the stress system into two parts. Neuronal activity is dominant upstream. Stress-signaling molecules produced by the neuroendocrine system are dominant downstream. We discuss the underlying molecular mechanisms by which CS impacts glioma. Potential pharmacological treatments are also summarized from the therapeutic perspective of CS.