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Abstract PANoptosis is one of several modes of programmed cell death (PCD) and plays an important role in many inflammatory and immune diseases. The role of PANoptosis in inflammatory bowel disease (IBD) is currently unknown. Differentially expressed PANoptosis-related genes (DE-PRGs) were identified, and pathway enrichment analyses were performed. LASSO regression model construction, a nomogram model, calibration curves, ROC and DCA curves were used to evaluate the predictive value of the model. Predicts transcription factors (TFs) and small-molecule drugs of DE-PRGs were analysed. Model genes and immuno-infiltration were analysed. The PANoptosis features of IBD include 12 genes: OGT, TLR2, GZMB, TLR4, PPIF, YBX3, CASP5, BCL2L1, CASP6, MEFV, GSDMB and BAX. The enrichment analysis suggested that these genes were related to TNF signalling, NF-κB, pyroptosis and necroptosis. Machine learning identified three model genes: OGT, GZMB and CASP5. The nomogram model, calibration curves, ROC and DCA curves have strong predictive value. Immuno-infiltration analysis revealed that immune cell infiltration was increased in patients with IBD, and the model genes were closely related to the infiltration of various immune cells. The TFs associated with DE-PRGs were RELA, NFKB1, HIF1A, TP53 and SP1. In addition, the Connectivity Map (CMap) database identified the top 10 small-molecule compounds, including buspirone, chloroquine, spectinomycin and chlortetracycline. This study indicate that DE-PRGs model genes have good predictive ability for IBD. Moreover, PANoptosis may mediate the process of IBD through TNF signalling, NF-κB, pyroptosis, necroptosis and immune mechanisms. These results present a new horizon for the research and treatment of IBD.

Background: In uremic patients, the accumulation of gut-derived protein-bound uremic toxins (PBUTs) induces changes in the microenvironment of the patients, leading to changes in the elimination pattern of drugs. Aims: To assess ways in which PBUTs alter the CYP450 enzymes in hepatocytes as well as the possible effects of specific PBUTs on the metabolism and excretion of atorvastatin (ATV). Study Design: An experimental study. Methods: The experimental group was treated with long-term MHD for > 3 months, estimated-glomerular filtration rate (e-GFR) < 15 ml/min, normal Alb level (35.0-55.0 g/l), and no urine; the control group was not treated with hemodialysis, e-GFR < 60 ml/min, normal Alb level, and normal urinary excretion function. A suitable UPLC-MS/MS method was developed for detecting the concentration of 4-hydroxy ATV. Fresh primary hepatocytes were isolated from rats, and the uptake of ATV was tested in the uremic serum (US) group, IS group, and HA group and compared with that in the normal serum group. The metabolic status of ATV in the US group, IS group, and HA group was compared with that in the ATV group. RLM were extracted, and the metabolic experiment of ATV was performed in a human CYP3A4 model. The influence of UTs on pregnane X receptor (PXR)/nuclear factor kappa B (NF-κB) mRNA and the protein expression was also detected. Results: IS and HA inhibited the ATV metabolism to varying degrees, wherein IS was the most potent inhibitor, producing > 50% inhibition. Meanwhile, the protein expression of CYP3A4 was downregulated after incubation with US, IS, and HA (p < 0.01). The excretion of ATV was also inhibited by 59.24% and 71.95% after incubation with IS and HA, respectively. The effects of uremic toxins on PXR/NF-κB mRNA and protein expression elucidated that PBUTs can inhibit ATV uptake and metabolism by exerting inhibitory effects on CYP3A4 through the PXR/NF-κB signaling pathway. Conclusion: ATV metabolism could be significantly altered in the presence of uremic toxins, suggesting a downregulated effect on the ATV uptake, possibly through Oatp1b1, and also on the activity of CYP3A4 through the PXR/NF-κB signaling pathway.

Background Lung cancer remains a significant global health challenge, with both its incidence and mortality rates on the rise worldwide. Despite numerous investigations into its etiology, progression, and prognostic indicators, a pressing need persists for straightforward and efficient methods to assess the early prognosis of lung cancer. Objective This study aims to investigate the prognostic significance of absolute eosinophil count level in patients with lung cancer. Methods We conducted a retrospective analysis of clinical data from 152 lung cancer patients admitted to the First Affiliated Hospital of Anhui Medical University between June 2019 and December 2022, with follow-up conducted until May 2023. Patients experiencing tumor recurrence, metastasis, or mortality were categorized into the poor prognosis group, while the remaining patients comprised the good prognosis group. Progression-free survival time (PFS) was meticulously recorded. Group comparisons were made to identify factors influencing lung cancer prognosis, followed by multivariate Cox regression analysis. Additionally, Kaplan-Meier survival analysis was employed to assess the impact of absolute eosinophil count on survival. Receiver operating characteristic (ROC) curve analysis was utilized to evaluate the prognostic efficacy of lung cancer, with the area under the ROC curve (AUC) calculated to gauge its predictive value. To further explore the relationship between eosinophil counts and lung cancer, datasets were procured from genome-wide association analysis pooled data and the International Consortium for Lung Cancer Research for Mendelian randomization analysis, elucidating potential causal links. Results Patients were stratified into good and poor prognosis groups based on their lung cancer prognosis. A statistically significant contrast in absolute eosinophil count was observed between these groups (P=0.004). Multivariate Cox regression analysis highlighted absolute eosinophil count as an independent risk factor for lung cancer survival outcomes (HR=1.58, 95%CI=1.03-2.44, P=0.037). Kaplan-Meier analysis revealed that the PFS time for patients with elevated absolute eosinophilic counts (n=76) (618.44±72.57 ) days was shorter compared to those with normal counts (n=76) (842.32±76.04) days (P=0.048). Furthermore, the AUC was 0.634. Mendelian randomization findings indicated that eosinophil count might serve as an adverse overall risk factor for lung cancer in the East Asian population (OR=1.07, 95%CI=1.01-1.13, P=0.030) . Conclusion The elevation of absolute eosinophil count levels may adversely impact the prognosis of lung cancer patients.

Abstract Aims/Introduction To assess whether the sodium–glucose cotransporter 2 inhibitor, henagliflozin, improves cognitive impairment in patients with type 2 diabetes. Materials and Methods We carried out a prospective study on 290 patients with type 2 diabetes and cognitive impairment. Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels were used to assess cognition. The association between henagliflozin use and changes in cognition was examined using multivariable logistic regression analysis. Results Montreal Cognitive Assessment scores at enrollment and after 6 months were 21 (interquartile range [IQR]19–23) versus 22 (IQR 20–25; P 0.05) in the non‐sodium–glucose cotransporter 2 inhibitor group. Logistic regression analysis showed that henagliflozin treatment was associated with Montreal Cognitive Assessment score improvement independent of potential confounders (odds ratio [OR] 3.670, 95% confidence interval [CI] 2.224–6.056, P

The utilization of activated carbon as an efficient adsorbent is well-established, driven by its porous structure and expansive surface area. This study investigates the potential of Cassia fistula (Golden shower) as a precursor for activated carbon synthesis using K2CO3 activation, leveraging its organic properties known for high porosity and adsorption capacity. This research aims to investigate the feasibility of utilizing Cassia fistula-derived activated carbon (GSAC) for isoniazid removal from water. The study encompasses a two-step activation process—chemical and physical—with varying parameters to optimize surface area and porosity. The carbonization process involves hydrothermal and pyrolysis techniques with controlled conditions. The temperature used in this study is based on the TGA analysis to examine its thermal stability. Batch experiments examine the adsorption equilibrium and kinetics of isoniazid onto GSAC samples, revealing high adsorption capacity and rapid equilibrium attainment by GSAC 1:1 (700°C). The study culminates in the identification of a strong chemical bond between GSAC and isoniazid, implying efficient adsorption potential as confirmed by FTIR and SEM analysis before and after adsorption. The adsorption characteristic is examined with an isotherm and kinetic model. The highest predicted GSAC capacity reaches 219,807 mg/g, emphasizing its promising adsorption capabilities. This work underscores Cassia fistula-based activated carbon as a viable, cost-effective, and eco-friendly adsorbent for isoniazid removal, with implications for diverse applications. The synthesis process parameters, activation methods, and insights into the adsorption mechanism contribute to the understanding of effective adsorbent production and enhance the potential of activated carbon for various industrial contexts.

Abstract Asthma and lung cancer are both significant public health concerns worldwide. Previous observational studies have indicated a potential link between asthma and an increased risk of lung cancer, whereas the causal relationship remains uncertain. We aimed to investigate the potential causal relationship between asthma and lung cancer risk utilizing Mendelian randomization (MR) design.The present study employed a two-sample MR analysis utilizing summary statistics from genome-wide association studies (GWAS) with European descent of asthma and lung cancer. The MR analysis was performed using inverse variance weighting (IVW), supplemented with MR-Egger regression and weighted median method to investigate the potential causality between asthma and lung cancer. Furthermore, Sensitivity analyses were also conducted to ensure the reliability of the findings. The MR analysis showed that genetically predicted asthma had suggestive causal association with the elevated risk of lung cancer [odds ratio (OR), 1.05 (95%Cl,1.01–1.09), P = 0.01]. The consistent direction of effects observed in the three methods further supported this finding. In addition, sensitivity analyses demonstrated the reliability of the results. This study provided potential evidence supporting a causal association between asthma and lung cancer. These findings highlighted the importance of early detection and prevention strategies for lung cancer in individuals with asthma. Further research was needed to elucidate the underlying mechanisms linking asthma and lung cancer.

Abstract HOX transcript antisense RNA (HOTAIR) is upregulated in glioblastoma (GBM) and associated with temozolomide (TMZ) resistance. However, the mechanisms underlying HOTAIR-mediated TMZ resistance remains poorly understood. HOTAIR expression in glioma-related public datasets and drug response estimation were analyzed using bioinformatics. These findings were verified by overexpressing HOTAIR in TMZ-sensitive U251 cells and/or silencing HOTAIR in resistant U251 cells (U251R). The cytotoxic effects were evaluated using cell viability assay and flow cytometry analysis of cell cycle and apoptosis. In this study, we found that HOTAIR was upregulated in TMZ-resistant GBM cell lines and patients with high HOTAIR expression responded poorly to TMZ therapy. HOTAIR knockdown restored TMZ sensitivity in U251R cells, while HOTAIR overexpression conferred TMZ resistance in U251 cells. Wnt/β-catenin signaling was enriched in patients with high HOTAIR expression; consistently, HOTAIR positively regulated β-catenin expression in U251 cells. Moreover, HOTAIR-mediated TMZ resistance was associated with increased MGMT protein level, which resulted from the HOTAIR/miR-214-3p/β-catenin network. Besides, GBM with high HOTAIR expression exhibited sensitivity to methotrexate. Methotrexate enhanced TMZ sensitivity in U251R cells, accompanied by reduced expression of HOTAIR and β-catenin. Thus, we conlcude that HOTAIR is a risk factor for TMZ resistance and methotrexate may represent a potential therapeutic drug for patients with high HOTAIR expression level.

Abstract Circadian disruption often arises prior to the onset of typical motor deficits in patients with Parkinson’s disease (PD). It remains unclear whether such a prevalent non-motor manifestation would contribute to the progression of PD. Diffusible oligomeric alpha-synuclein (O-αSyn) is perceived as the most toxic and rapid-transmitted species in the early stages of PD. Exploring the factors that influence the spread and toxicity of O-αSyn should be helpful for developing effective interventions for the disease. The aim of this study was to explore the effects of circadian disruption on PD pathology and parkinsonism-like behaviors in a novel mouse model induced by O-αSyn. We discovered that O-αSyn could enter the brain rapidly following intranasal administration, resulting in the formation of nitrated-αSyn pathology and non-motor symptoms of the mice. Meanwhile, circadian disruption exacerbated the burden of nitrated-αSyn pathology and accelerated the loss of dopaminergic neurons in O-αSyn-treated mice. Subsequent experiments demonstrated that circadian disruption might act via promoting nitrative stress and neuroinflammation. These findings could highlight the circadian rhythms as a potential diagnostic and therapeutic target in early-stage PD.

Neurodegenerative diseases (ND) are characterized by the accumulation of aggregated proteins. The glymphatic system, through its rapid exchange mechanisms between cerebrospinal fluid (CSF) and interstitial fluid (ISF), facilitates the movement of metabolic substances within the brain, serving functions akin to those of the peripheral lymphatic system. This emerging waste clearance mechanism offers a novel perspective on the removal of pathological substances in ND. This article elucidates recent discoveries regarding the glymphatic system and updates relevant concepts within its model. It discusses the potential roles of the glymphatic system in ND, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple system atrophy (MSA), and proposes the glymphatic system as a novel therapeutic target for these conditions.

Taste preference drives food selection, acceptance, or rejection and influences nutritional status and body mass index. Nevertheless, there are few reports concerning pregnant women. Mala flavor, characterized by its “numbing” and “spicy” sensations, is a distinctive taste of Sichuan cuisine, created by the combination of Chinese prickly ash and chili peppers. We conducted a cohort study in Chongqing, China to analyze the impact of Mala flavor, on excessive gestational weight gain (GWG). The study included 495 pregnant women aged 20–45 years, without chronic diseases, who conceived naturally and had single pregnancies from May 2021 to November 2022. Demographic information and pregnancy outcomes were collected during the second trimester and post-delivery, respectively. Food intake and taste preferences, including fatty, salty, and Mala flavors, were assessed during the third trimester. Latent Profile Analysis revealed three dietary patterns: “high-carbohydrate diet” (HCD), “low-carbohydrate diet” (LND), and “moderate nutrient diet” (MND). Multiple logistic regression indicated that pregnant women preferring Mala flavor were more likely to follow an HCD and had a higher risk of excessive GWG. Moreover, those adhering to an HCD were at an increased risk of excessive GWG. Mediation analysis showed that the preference for Mala flavor influenced excessive GWG through HCDs, with a significant indirect effect and an insignificant direct effect. Our study suggests that a preference for Mala flavor is positively associated with excessive GWG, mediated by HCD patterns. However, these findings should be approached with caution due to the exploratory nature of the study.

Background: Recent research suggests that the emerging neutrophil-albumin ratio (NAR) has a significant correlation with the survival outcomes across a range of tumors, yet its predictive significance for nasopharyngeal carcinoma (NPC) remains insufficiently investigated. This study aimed to evaluate the relationship between the neutrophil-to-albumin ratio (NAR) and overall survival (OS) in patients with NPC, as well as to develop a corresponding prognostic model. Methods: This retrospective analysis included 861 NPC patients treated with concurrent chemoradiotherapy (CCRT), who were randomly divided into a training group (n = 605) and a validation group (n = 256). To identify factors associated with OS and construct a prognostic nomogram, both univariate and multivariate Cox regression analyses were performed. The nomogram's prognostic accuracy was evaluated and independently validated. Results: The NAR score successfully segregated NPC patients into two categories with significantly different OS (HR = 0.536; 95 % CI: 0.296–0.972, P = 0.040). Through multivariate analysis, factors such as age, T stage, N stage, and NAR score were identified as independent predictors of OS, leading to the creation of a prognostic nomogram. This nomogram demonstrated superior predictive capability for OS [C-index = 0.702 (95 % CI: 0.636–0.768)], surpassing that of the conventional staging system [C-index = 0.651 (95 % CI: 0.549–0.752)]. The findings underwent internal validation within an independent cohort. Conclusions: The NAR, an emergent biomarker combining nutritional and inflammatory status, offers a practical, low-cost, and non-invasive prognostic measure for NPC patients treated with CCRT. Additionally, the prognostic nomogram derived from NAR surpasses traditional staging systems in predictive accuracy.

BackgroundHelicobacter pylori (H. pylori) may be present in the intestinal mucosa of patients with inflammatory bowel disease (IBD), which is a chronic inflammation of the gastrointestinal tract. The role of H. pylori in the pathogenesis of IBD remains unclear. In this study, bioinformatics techniques were used to investigate the correlation and co-pathogenic pathways between H. pylori and IBD.MethodsThe following matrix data were downloaded from the GEO database: H. pylori-associated gastritis, GSE233973 and GSE27411; and IBD, GSE3365 and GSE179285. Differential gene analysis was performed via the limma software package in the R environment. A protein−protein interaction (PPI) network of DEGs was constructed via the STRING database. Cytoscape software, through the CytoHubba plugin, filters the PPI subnetwork and identifies Hub genes. Validation of the Hub genes was performed in the validation set. Immune analysis was conducted via the CIBERSORT algorithm. Transcription factor interaction and small molecule drug analyses of the Hub genes were also performed.ResultsUsing the GSE233973 and GSE3365 datasets, 151 differentially expressed genes (DEGs) were identified. GO enrichment analysis revealed involvement in leukocyte migration and chemotaxis, response to lipopolysaccharides, response to biostimulatory stimuli, and regulation of interleukin-8 (IL-8) production. Ten Hub genes (TLR4, IL10, CXCL8, IL1B, TLR2, CXCR2, CCL2, IL6, CCR1 and MMP-9) were identified via the PPI network and Cytoscape software. Enrichment analysis of the Hub genes focused on the lipopolysaccharide response, bacterial molecular response, biostimulatory response and leukocyte movement. Validation using the GSE27411 and GSE179285 datasets revealed that MMP-9 was significantly upregulated in both the H. pylori and IBD groups. The CIBERSORT algorithm revealed immune infiltration differences between the control and disease groups of IBD patients. Additionally, the CMap database identified the top 11 small molecule compounds across 10 cell types, including TPCA-1, AS-703026 and memantine, etc.ConclusionOur study revealed the co-pathogenic mechanism between H. pylori and IBD and identified 10 Hub genes related to cellular immune regulation and signal transduction. The expression of MMP-9 is significantly upregulated in both H. pylori infection and IBD. This study provides a new perspective for exploring the prevention and treatment of H. pylori infection and IBD.

On 8 October 2017, persistent heavy rainfall triggered a rock collapse on Fenghuang Mountain in Wuxi Town, located within the Three Gorges Reservoir region of China. Subsequent field investigations and monitoring identified several potentially unstable rock masses in the area, posing a significant threat to the safety of nearby residents and their property. In this study,the Rapid Mass Movement Simulation (RAMMS) numerical tool was used to perform a back analysis of the rock collapse event. The well calibrated numerical model was then used to assess the risk of the potential unstable rock masses in the study area. The rock collapse on Fenghuang Mountain descended rapidly along the slope, with the dislodged material accumulating at the base and obstructing the road at the foot of the slope. Some debris breached the embankment and entered the Daning River. The computed maximum velocity during the rock collapse event was approximately 9.14 m/s, with an average maximum deposit thickness of around 4.48 m. The back-analysis of the rock collapse event closely aligns with the observed failure process and deposit morphology documented through field investigation. Using the well calibrated numerical model, a dynamic analysis was conducted on the potential unstable rock mass. The risk assessment indicates that the potential unstable rock mass is prone to instability, with a high likelihood of a subsequent rockfall under extreme rainfall conditions. The computed average maximum velocity for the potential rockfall is 33.83 m/s, with an average maximum deposit thickness of 2.20 m. The computed maximum impact pressure is about 164 kPa, which would result in significant damage to the road below. Additionally, a maximum wave height of 1.38 m from the surge caused by potential rockfall entering the Daning River was calculated by a semi-empirical model. This research offers a novel approach and methodology for assessing the risk of such hazardous events in similar geological setting globally.

Objective: Acute myeloid leukemia (AML) stands out as a malignancy of the stem cell precursors of the myeloid lineage. Bone-marrow mesenchymal stem cell-derived exosomes (BMSC-exos) affect AML progression. We explored the effects and mechanism of BMSC-exos on AML cell proliferation and apoptosis.Methods: Human AML cells (MOLM-16, MV-4-11) and normal human hematopoietic cells (GM12878) cultured in vitro were treated with exos extracted from BMSCs that transfected with microRNA (miR)-139-5p-mimics, ovβ-catenin, or miR-139-5p-inhibitor. BMSC morphology was observed by a microscopy, and its adipogenic and osteogenic differentiation abilities were assessed by oil red O staining and alizarin red S staining. BMSC-exos were extracted by ultracentrifugation, and their morphology was observed by a transmission electron microscopy. BMSC-exos were identified by nanoparticle tracking analysis and Western blot. The binding sites between miR-139-5p and β-catenin were predicted by TargetScan database, and then validated by dual-luciferase reporter assay. mRNA levels of miR-139-5p and β-catenin, cell proliferation, and apoptosis were evaluated by RT-qPCR, CCK-8, and flow cytometry. The expressions of CD63, CD81, TSG101, and GRP94 and the proteins of β-catenin, Bax, and Bcl-2 were determined by Western blot.Results: miR-139-5p was poorly expressed in AML cell lines. miR-139-5p overexpression reduced AML cell viability/proliferation/Bcl-2 level, and raised apoptosis/Bax level. BMSC-exos repressed AML cell proliferation and promoted apoptosis via miR-139-5p. miR-139-5p targeted to inhibit β-catenin expression. Subsequently, up-regulated β-catenin partially counteracted the effects of miR-139-5p in BMSC-exos on AML cell proliferation and apoptosis.Conclusion: BMSC-exos targeted to repress β-catenin expression by miR-139-5p, limited AML cell proliferation and facilitated apoptosis.

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redoxhigh LUAD and redoxlow LUAD. Genetically, redoxhigh LUAD is mainly driven by mutations in KEAP1, STK11, NRF2, or SMARCA4. These mutations are more prevalent in redoxhigh LUAD (72.5%) compared to redoxlow LUAD (17.4%), whereas EGFR mutations are more common in redoxlow LUAD (19.0% vs. 0.7%). Single-cell RNA profiling of pre-treatment and post-treatment samples from patients receiving neoadjuvant chemoimmunotherapy revealed that tissue-resident memory CD8+ T cells are responders to ICIs. However, these cells are significantly reduced in redoxhigh LUAD. The redoxhigh phenotype is primarily attributed to tumor cells and is positively associated with mTORC1 signaling. LUAD with the redoxhigh phenotype demonstrates a lower response rate (39.1% vs. 70.8%, p = 0.001), shorter progression-free survival (3.3 vs. 14.6 months, p = 0.004), and overall survival (12.1 vs. 31.2 months, p = 0.022) when treated with ICIs. The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.

Candida albicans is an opportunistic fungal pathogen that can cause systemic infections in immunocompromised individuals. Morphological transition and biofilm formation are major virulence factors of C. albicans. Moreover, biofilm enhances resistance to antifungal agents. Therefore, it is urgent to identify new and effective compounds to target the biofilm of C. albicans. In the present study, the antifungal activities of equol against C. albicans were investigated. In vitro, the microdilution analysis and spot assay result showed that equol exhibited potent inhibitory activities against C. albicans. Further investigations confirmed that the antifungal effects of equol involved interference with the transition from yeast to hypha and biofilm formation of C. albicans. In addition, transcriptome sequencing and reverse transcription-quantitative PCR (qRT-PCR) analysis showed that equol significantly downregulated the expression of several genes in the Ras1-cAMP-PKA pathway related to hyphae and biofilm formation and significantly upregulated the expression of the negative transcriptional repressors RFG1 and TUP1. Moreover, equol effectively reduced the production of cAMP, a key messenger in the Ras1-cAMP-PKA pathway, while supplementation with cAMP partly rescued the equol-induced defects in hyphal development. Furthermore, in a mouse model of systemic candidiasis (SC), equol treatment significantly decreased the fungal burden (liver, kidneys, and lung) in mice and local tissue damage, while enhancing the production of interleukin-10 (IL-10). Together, these findings confirm that equol is a potentially effective agent for treatment of SC.

Purpose: There is very little information detailing outcomes and toxicity following reirradiation for ultracentrally located thoracic tumors, and detailed dosimetric data are nonexistent. These data are critical for the safe management of these extremely difficult cases. Methods and Materials: The records of 15 individuals undergoing 10-fraction hypofractionated stereotactic body radiation therapy for the management of ultracentrally located thoracic tumors between 2009 and 2020 at a single institution were retrospectively reviewed. Treatment outcomes and toxicity were analyzed. A detailed dosimetric analysis of treatment plans and centrally located organs at risk (OARs) from the initial reirradiation and cumulative radiation therapy courses were presented. Results: At a median follow up of 10 months, the 1- and 3-year overall survival, progression-free survival, and local control were 52% and 28%, 33% and 28%, and 76% and 61%, respectively. Treatment-related adverse events were low, with 5 individuals (33%) developing ≥grade 2 pneumonitis (grade 2 = 4, grade 3 = 1). Dosimetric parameters were not associated with the development of clinically relevant pneumonitis. No adverse events involving central OARs (esophagus, great vessels, and primary bronchial tree) were identified. The median cumulative mean lung dose was 24 Gy equivalent total doses in 2 Gy fractions (EQD2) (range, 10-33 Gy), with a volume receiving 20 G (V20) of 33% (range, 11%-51%). The median esophageal, primary bronchial tree, and great vessel maximum doses (Dmax) were 93.2 Gy (EQD2) (range, 50-148 Gy), 163 Gy (range, 77-204 Gy), and 191 Gy (range, 129-262 Gy), respectively. Conclusions: The current investigation is the first to provide detailed cumulative dosimetric data from a cohort of patients comprised entirely of ultracentrally located thoracic tumors. Despite unfavorable anatomic tumor location, given an intimate association with critical OARs, delivering an ablative dose with a 10-fraction hypofractionated stereotactic body radiation therapy course can serve as a feasible option for these challenging cases.

Abstract Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson’s disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene (GBA) increase the risk of PD. Here, we developed a mouse model characterized by sleep–wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2–10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA-AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.

Abstract In the process of group recommendation, due to the different preferences of group members, the recommendation results cannot meet the needs of all users. How to maximize the fairness of group recommendation is still a challenge. Therefore, this paper proposes a group recommendation algorithm based on user activity. Firstly, a group discovery algorithm based on item cluster preference was used to mine potential groups. Secondly, considering the dynamic change of activity, a sliding time window is designed to investigate the recent activity of each member in the group at the time of subgroup division, and the group is divided into active subgroup and inactive subgroup. Finally, the group recommendation list was generated by aggregating the subgroup preferences by average consensus. Experimental results on the public dataset show that compared with the AGREE algorithm, the recommendation accuracy and coverage of the proposed algorithm are improved by 2.1% and 2.9%, respectively. By focusing on the preference needs of inactive users, the proposed algorithm effectively improves the recommendation satisfaction and group fairness.

Abstract Background Recently, the hemoglobin to albumin ratio (HAR) has been shown to be closely associated with the survival of certain malignancies. However, its prognostic value in nasopharyngeal carcinoma (NPC) remained to be elucidated. Herein, we aimed to explore the correlation between HAR and overall survival (OS) in NPC patients treated with concurrent chemoradiotherapy (CCRT). Methods This retrospective study included a total of 858 patients with NPC receiving CCRT between January 2010 and December 2014 in Sun Yat-sen University Cancer Center. We randomly divided them into the training cohort (N = 602) and the validation cohort (N = 206). We performed univariate and multivariate Cox regression analyses to identify variables associated with OS, based on which, a predictive nomogram was constructed and assessed. Results In both the training and validation cohorts, patients were classified into low- and high-HAR groups according to the cutoff value determined by the maximally selected rank statistics. This HAR cutoff value effectively divided patients into two distinct prognostic groups with significant differences. Multivariable Cox analysis revealed that higher T-stage, N-stage, and HAR values were significantly related to poorer prognosis in NPC patients and served as independent prognostic factors for NPC. Based on these, a predictive model was constructed and graphically presented as a nomogram, whose predictive performance is satisfactory with a C-index of 0.744 [95%CI: 0.679–0.809] and superior to traditional TNM staging system [C-index = 0.609, 95%CI: 0.448–0.770]. Conclusion The HAR value was an independent predictor for NPC patients treated with CCRT, the predictive model based on HAR with superior predictive performance than traditional TNM staging system might improve individualized survival predictions.

Abstract. The usage of electronic cigarettes (e-cigarettes) sparked an outbreak of unidentified vaping-related lung disease in the US during late 2019. With e-cigarettes becoming more and more popular, smokers have more options other than conventional cigarettes. Under these circumstances, a comprehensive evaluation of the general safety of new tobacco and tobacco-related products, represented by e-cigarettes, to human health is necessary. In this review, we summarize the current research on potential negative impacts of e-cigarette exposure on human health. In particular, studies detailing the relationship between e-cigarettes and the digestive system are summarized, with mechanisms mainly including hepatic metabolic dysfunction, impaired gut barrier, and worsened outcomes of inflammatory bowel disease (IBD). Although believed to be safer than traditional cigarettes, e-cigarettes exert adverse effects on systemic health and induce the development of multiple diseases including asthma, cardiovascular disease, and IBD. Moreover, nicotine-containing e-cigarettes have a negative impact on the childhood development and increase the risk of arterial stiffness compared to the non-nicotine e-cigarettes. However, non-nicotine e-cigarette components have detrimental effects including promoting liver damage and metabolic disorders.

Abstract Translational control plays a crucial role in the regulation of apoptosis, with the EIF4 family serving as one of the mRNA translation factors that modulate the process of mRNA translation based on mRNA characteristics. To address this potential causal role of EIF4 family proteins and breast cancer, Mendelian randomization was employed. The study incorporated four sets of genetics instrumental variables, namely EIF4E, EIF4B, EIF4A, and EIF4EBP2. The outcome variables selected for analysis were the BCAC consortium, which included estrogen receptor positive (ER+) and estrogen receptor negative (ER−) samples. To assess the potential violations of the MR assumption, the primary MR analysis employed inverse variance weighted (IVW), and several sensitivity analyses were conducted. The findings of the two-sample MR analysis indicate that EIF4E has an adverse effect on breast cancer risk (p = 0.028). However, the evidence for the relationship between EIF4E and ER status of breast cancer suggests a weak association with ER+ breast cancer (p = 0.054), but not with ER- breast cancer (p > 0.05). The study findings indicate that EIF4A is not causally linked to the risk of ER+ breast cancer, but is significantly associated with an elevated risk of ER− breast cancer (p = 0.028). However, the evidence is inadequate to support the effects of EIF4B and EIF4EBP2 on breast cancer (p > 0.05). Our results suggest that EIF4 may be a potential factor in the occurrence and development of breast cancer, which may lead to a better understanding of its causes and prevention.

Abstract Background Gliomas are the deadliest malignant tumors of the adult central nervous system. We previously discovered that beta2-microglobulin (B2M) is abnormally upregulated in glioma tissues and that it exerts a range of oncogenic effects. Besides its tissue presence, serum B2M levels serve as biomarkers for various diseases. This study aimed to explore whether serum B2M levels can be used in the diagnosis and prognosis of gliomas. Methods Medical records from 246 glioma patients were retrospectively analyzed. The relationship between preoperative serum B2M levels and clinicopathological features was examined. Kaplan-Meier analysis, alongside uni- and multivariate Cox regression, assessed the association between B2M levels, systemic inflammatory markers, and glioma patient prognosis. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic significance of these biomarkers specifically for glioblastoma (GBM). Results Patients with malignant gliomas exhibited elevated preoperative serum B2M levels. Glioma patients with high serum B2M levels experienced shorter survival times. Multivariate Cox analysis determined the relationship between B2M levels (hazard ratio = 1.92, 95% confidence interval: 1.05–3.50, P = 0.034) and the overall survival of glioma patients. B2M demonstrated superior discriminatory power in distinguishing between GBM and non-GBM compared to inflammation indicators. Moreover, postoperative serum B2M levels were lower than preoperative levels in the majority of glioma patients. Conclusions High preoperative serum B2M levels correlated with malignant glioma and a poor prognosis. Serum B2M shows promise as a novel biomarker for predicting patient prognosis and reflecting the therapeutic response.

Objective: This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex (MAC), considering BDQ as a repurposed drug for non-tuberculous mycobacteria (NTM) infections. Methods: We conducted a systematic review of publications in PubMed/ MEDLINE, Web of Science, and Embase up to 15 April 2023. Studies were included if they followed the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). Using a random effects model, we assessed the overall in vitro BDQ resistance rate in clinical isolates of MABS and MAC. Sources of heterogeneity were analysed using Cochran's Q and the I2 statistic. All analyses were performed using CMA V3.0. Results: A total of 24 publications (19 reports for MABS and 11 for MAC) were included. Using 1 µg/mL and 2 µg/mL as the breakpoint for BDQ resistance, the pooled rates of in vitro BDQ resistance in clinical isolates of MABS were found to be 1.8% (95% confidence interval [CI], 0.7–4.6%) and 1.7% (95% CI, 0.6–4.4%), respectively. In the case of MAC, the pooled rates were 1.7% (95% CI, 0.4–6.9%) and 1.6% (95% CI, 0.4–6.8%) for 1 µg/mL and 2 µg/mL, respectively. Conclusion: This study reports the prevalence of BDQ resistance in clinical isolates of MABS and MAC. The findings suggest that BDQ holds potential as a repurposed drug for treating MABS and MAC infections.

Abstract Background Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. Methods We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram’s predictive accuracy to rigorous independent validation. Results The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28–0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64–0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65–0.74). Conclusions In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.

Global temperatures will continue to increase in the future. The ∼640,000-km2 Loess Plateau (LP) is a typical arid and semi-arid region in China. Similar regions cover ∼41% of the Earth, and its soils are some of the most severely eroded anywhere in the world. It is very important to understand the vegetation change and its ecological threshold under climate change on the LP for the sustainable development in the Yellow River Basin. However, little is known about how vegetation on the LP will respond to climate change and what is the sustainable threshold level of vegetation cover on the LP. Here we show that the temperature on the LP has risen 0.27 °C per decade over the past 50 years, a rate that is 30% higher than the average warming rate across China. During historical times, vegetation change was regulated by environmental factors and anthropogenic activities. Vegetation coverage was about 53% on the LP from the Xia Dynasty to the Spring and Autumn and Warring States period. Over the past 70 years, however, the environment has gradually improved and the vegetation cover had increased to ∼65% by 2021. We forecast future changes of vegetation cover on the LP in 2030s, in 2050s and in 2070s using SDM (Species Distribution Model) under Low-emission scenarios, Medium-emission scenarios and High-emission scenarios. An average value of vegetation cover under the three emission scenarios will be 64.67%, 62.70% and 61.47%, respectively. According to the historical record and SDM forecasts, the threshold level of vegetation cover on the LP is estimated to be 53–65%. Currently, vegetation cover on the LP has increased to the upper limit of the threshold value (∼65%). We conclude that the risk of ecosystem collapse on the LP will increase with further temperature increases once the vegetated area and density exceed the threshold value. It is urgent to adopt sustainable strategies such as stopping expanding vegetation area and scientifically optimizing the vegetation structure on the LP to improve the ecological sustainability of the Yellow River Basin.

Shallow landslides and debris flows triggered by heavy rainfall are widespread catastrophic geological disasters in mountainous areas. Landslides with complex terrain are often the material source of debris flows as a disaster chain. However, the failure mechanism and dynamic process of landslide triggered debris flow are still not clear. In July 2023, an obvious rockslide occurred during heavy rainfall in Changtan Town, Chongqing City, Southwest China, resulting in one death and seven houses collapsed. In this paper, back analysis in the dynamic process of the Yanghuachi (YHC) landslide triggered debris flow is carried out by the coupled particle flow model and elastic viscoplastic model. The reults indicate that the sliding body moves downward along the sliding surface, pushing the loose deposits at the lower part of the landslide to slip and then extending along the gully to the right bank of the Modao River. The overall movement duration of the landslide in the study area is approximately 180 s, with a maximum sliding velocity of about 22.08 m/s and a final deposition thickness of approximately 10.91 m. This study provides a methodology for analyzing the dynamic process of landslide triggered debris flows.

Nitrogen (N) is an essential element for plant growth, development, and metabolism. In apple production, the excessive use of N fertilizer may cause high N stress. Whether high N stress can be alleviated by regulating melatonin supply is unclear. The effects of melatonin on root morphology, antioxidant enzyme activity and 13C and 15N accumulation in apple rootstock M9T337 treated with high N were studied by soil culture. The results showed that correctly raising the melatonin supply level is helpful to root development of M9T337 rootstock under severe N stress. Compared with HN treatment, HN+MT treatment increased root and leaf growth by 11.38%, and 28.01%, respectively. Under high N conditions, appropriately increasing melatonin level can activate antioxidant enzyme activity, reduce lipid peroxidation in roots, protect root structural integrity, promote the transport of sorbitol and sucrose to roots, and promote further degradation and utilization of sorbitol and sucrose in roots, which is conducive to the accumulation of photosynthetic products, thereby reducing the inhibitory effect of high N treatment on root growth. Based on the above research results, we found that under high N stress, melatonin significantly promotes nitrate absorption, enhances N metabolism enzyme activity, and upregulates related gene expression, and regulate N uptake and utilization in the M9T337 rootstock. These results presented a fresh notion for improving N application and preserving carbon-nitrogen balance.

Objective To explore the predictive value of serum levels of endothelial nitric oxide synthase (eNOS) and Omentin-1 for the occurrence of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients. Methods From May 2020 to February 2023, 124 hospitalized patients with type 2 DKD were selected as DKD group and 125 patients with simple type 2 diabetes as control group. Clinical parameters of all patients were collected. Serum levels of eNOS and Omentin-1 were detected by enzyme-linked immunosorbent assay (ELISA). Pearson’s method was utilized for examining the correlation between serum eNOS, Omentin-1 and clinical parameters. Multivariate Logistic regression model was employed for examining the risk factors of DKD occurrence in T2DM. The predictive value of serum levels of eNOS and Omentin-1 for the occurrence of DKD was examined by receiver operating characteristic (ROC) curve. Results As compared with control group, serum levels of total cholesterol [(4.75±0.91) mmol/L vs (4.48±0.96) mmol/L], glycosylated hemoglobin [(9.32±1.25)% vs (8.56±1.23)%], 24 h urinary protein quantity [(2.78±0.31) g vs (0.15±0.02) g], urinary microalbumin (mAlb) [(273.12±20.41) mg/L vs (23.08±3.35) mg/L] and serum creatinine (Scr) [(209.53±22.59) μmol/L vs (73.52±9.21) μmol/L] spiked markedly in DKD group. And the levels of estimated glomerular filtration rate (eGFR) [(72.52±13.51) mL·min−1·(1.73 m2)−1 vs (107.34±10.27) mL·min−1·(1.73 m2)−1], serum eNOS [(24.48±3.37) U/L vs (33.82±4.52) U/L] and Omentin-1 [ (28.75±4.42) μg/L vs (43.63±6.78) μg/L] rose sharply (P

Abstract Background On December 7, 2022, the Joint Prevention and Control Mechanism of China’s State Council released the “Ten New Guidelines” to optimize the coronavirus disease 2019 (COVID-19) prevention policies further. This signaled a broader shift from “dynamic clearing” to “coexisting with the virus” nationwide. Objective This study aims to examine the experiences and perspectives of interdisciplinary nurses during the COVID-19 outbreak in China after the implementation of the “Ten New Guidelines”. The goal is to understand the challenges faced by this unique nursing group and inform organizational support to bolster their well-being and resilience. Methods Two tertiary hospitals in southeastern Zhejiang Province were selected, with interdisciplinary nurses chosen as subjects. A constructivist qualitative research approach was employed, using semi-structured face-to-face interviews. Research data were collected through interviews and analyzed using content analysis. Results Fifteen interdisciplinary nurses were included in this study. The analysis revealed four main themes and nine sub-themes. The main themes were: (1) ineffective organizational support (inadequate organizational care, poor PPE, excessive workload), (2) physiological distress after contracting COVID-19 (extreme physical fatigue, leakage of urine due to severe coughing), (3) fear of being wrong (fear of being reprimanded in public, psychological anxiety), and (4) family responsibility anxiety (difficulty of loyalty and filial piety, obligations to their children). Conclusion We provide new evidence that organizations must proactively address the support, training, and communication needs of staff, particularly interdisciplinary nurses, to supplement epidemic containment. This is also essential in helping mitigate the work-family conflicts such roles can create.

Abstract Background Incubation behaviour, an instinct for natural breeding in poultry, is strictly controlled by the central nervous system and multiple neuroendocrine hormones and neurotransmitters, and is closely associated with the cessation of egg laying. Therefore, it is essential for the commercial poultry industry to clarify the molecular regulation mechanism of incubation behaviour. Here, we used high-throughput sequencing technology to examine the pituitary transcriptome of Changshun green-shell laying hen, a local breed from Guizhou province, China, with strong broodiness, in two reproductive stages, including egg-laying phase (LP) and incubation phase (BP). We also analyze the differences in gene expression during the transition from egg-laying to incubation, and identify critical pathways and candidate genes involved in controlling the incubation behaviour in the pituitary. Results In this study, we demonstrated that a total of 2089 differently expressed genes (DEGs) were identified in the pituitary, including 842 up-regulated and 1247 down-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that steroid biosynthesis pathway and neuroactive ligand-receptor interaction were significantly enriched based on DEGs commonly identified in pituitary. Further analysis revealed that SRC, ITGB4, ITGB3, PIK3R3 and DRD2 may play crucial roles in the regulation of incubation behaviour. Conclusions We identified 2089 DEGs and the key signaling pathways which may be closely correlated with incubation in Changshun green-shell laying hens, and clarified the molecular regulation mechanism of incubation behaviour. Our results indicate the complexity and variety of differences in reproductive behaviour of different chicken breeds.

Abstract Hiptage yangshuoensis K.Tan & K.S.Nguyen, a new species of Hiptage collected from a karst cliff close to the Lijiang River, Northeast of Guangxi Zhuang Autonomous Region, China, is described and illustrated based on molecular and morphological data. Hiptage yangshuoensis shares some morphological similarities with the H. multiflora F.N.Wei, but easily distinguished by its long pedicels with articulate at top, one large calyx gland, oblanceolate middle wing and lanceolate lateral wings of samara, and young branch covered rusty sericeous. The new species status is also supported by molecular phylogenetic analyses based on nuclear ribosome internal transcribed spacer (nrITS), which showed distinct systematic distinctiveness from the most morphologically similar species, H. multiflora.

Summary: Background: Current surveillance modalities of osteosarcoma relapse exhibit limited sensitivity and specificity. Although circulating tumor DNA (ctDNA) has been established as a biomarker of minimal residual disease (MRD) in many solid tumors, a sensitive ctDNA detection technique has not been thoroughly explored for longitudinal MRD detection in osteosarcoma. Methods: From August 2019 to June 2023, 59 patients diagnosed with osteosarcoma at the First Affiliated Hospital of Sun Yat-sen University were evaluated in this study. Tumor-informed MRD panels were developed through whole exome sequencing (WES) of tumor tissues. Longitudinal blood samples were collected during treatment and subjected to multiplex PCR-based next-generation sequencing (NGS). Kaplan–Meier curves and Log-rank tests were used to compare outcomes, and Cox regression analysis was performed to identify prognostic factors. Findings: WES analysis of 83 patients revealed substantial mutational heterogeneity, with non-recurrent mutated genes accounting for 58.1%. Tumor-informed MRD panels were successfully obtained for 85.5% of patients (71/83). Among 59 patients with successful MRD panel customization and available blood samples, 13 patients exhibited positive ctDNA detection after surgery. Patients with negative post-operative ctDNA had better event-free survival (EFS) compared to those with positive ctDNA, at 1–6 months after surgery, after adjuvant chemotherapy, and more than 6 months after surgery (p

White light emitting diodes (wLEDs) have been widely used as the green lighting sources. The commercial wLEDs devices are mainly achieved through the combination of blue emission chips and yellow phosphors, which offer advantages of high efficiency and long lifetime. However, the color rendering index (CRI) of traditional wLEDs is low due to the lack of red components. In recent years, with the improvement of the quality of life, a lot of efforts have been paid to improve the performance of wLEDs devices related to CRI, correlated color temperature, light uniformity, luminous flux, etc. In this article, we summarize the recent advances on the optimization of wLEDs toward healthy lighting. Brief introductions on the fundamentals of healthy effect of lighting are presented, followed by discussions of current methods to realize wLEDs devices. Special overviews on strategies for luminescent materials of wLEDs in recent years are presented. The opportunities and challenges in the future development of wLEDs lighting devices are also discussed.

Folic acid (FA) is an essential vitamin for the growth and health of aquatic organisms in the aquaculture industry. The purpose of this study was to investigate the effects and potential mechanisms of action of dietary FA on the growth and immune response of red swamp crayfish (Procambius clarkii). Crayfish (n = 360; 3 tanks of 20 crayfish for each dietary treatment) were fed diets containing different levels of FA (0 [control], 0.5, 1, 2, 4, and 8 mg/kg dry feed weight) for 60 d. Broken-line analysis based on the final weight and specific growth rate revealed that the optimal dietary FA level for promoting growth was 2 mg/kg. Villus length, lipase activity, and antioxidant superoxide dismutase activity significantly increased under the 2 mg/kg treatment. Transcriptome analysis identified 177 upregulated and 298 downregulated differentially expressed genes (DEGs) between the 0 (control) and 2 mg/kg groups. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the most significantly enriched pathways were related to glucose metabolism. Among the DEGs involved in glucose metabolism, Tpi1 (triosephosphate isomerase 1) and Pck1 (phosphoenolpyruvate carboxykinase 1) were upregulated and downregulated under FA treatment, respectively. Our findings suggest that the optimal dietary FA requirement for crayfish is 2 mg/kg and that dietary FA may enhance nutrient bioavailability and regulate glucose metabolism to improve crayfish growth performance.

This meta-analysis aims to clarify the relationship between teacher-child interaction and children's outcomes in language, mathematics, literacy, social development, and self-regulation based on the perspective of the Classroom Assessment Scoring System (CLASS). A total of 24 studies with 139 independent effect sizes and 67,919 participants were included through literature search and screening. The results show that CLASS is moderately correlated with children's outcomes in language, mathematics, self-regulation, and correlated with children's literacy and social development to a low degree. Apart from within-domain links to children's outcomes, most CLASS domains have cross-domain links to children's outcomes. These links are also influenced to varying degrees by the level of economic and social development, children's commonly used language, child outcome measurement tools, and the emotional support domain score of CLASS. Future studies should standardize the presentation of key information and explore the interaction of multiple variables.

Abstract Plain pottery excavated from the Tang Dynasty tomb of Liu Jing was taken as the research object. The color, chemical composition, microstructure, and phase were tested to investigate the influencing factors of color for plain pottery fragments. The results indicated that the contents of Fe2O3 and TiO2 in all fragments varied little, and the influence of humic acids in clay as well as the firing atmosphere on the appearance color of plain pottery was excluded. Therefore, the main factor affecting color saturation (C*) was identified as the firing temperature (T). More importantly, the correlation between C* and firing temperature was established by replicas fired at different temperatures. Before the appearance of the glass phase, iron-containing minerals played a major role in coloring, and after that, iron ions in the glass phase and iron crystallization rose the important function of coloring. Consequently, with the increase of firing temperature, C* value increased firstly and then decreased. The inflection point of the fitted C* − T curve corresponded to the glass phase formation temperature. By comparing the estimated firing temperatures obtained by the fitted C* − T correlation curve with the known firing temperature of replicas, it was demonstrated that the color measurement is an ideal method for deducing the firing temperatures of ancient plain pottery.

In this paper, we provide a new simple proof of a double inequality of Masjed-Jamei type proved by L. Zhu [1].

Abstract Background To develop and validate a preoperative nomogram model combining the radiomics signature and clinical features for preoperative prediction of visceral pleural invasion (VPI) in lung nodules presenting as part‐solid density. Methods We retrospectively reviewed 156 patients with pathologically confirmed invasive lung adenocarcinomas after surgery from January 2016 to August 2019. The patients were split into training and validation sets by a ratio of 7:3. The radiomic features were extracted with the aid of FeAture Explorer Pro (FAE). A CT‐based radiomics model was constructed to predict the presence of VPI and internally validated. Multivariable regression analysis was conducted to construct a nomogram model, and the performance of the models were evaluated with the area under the receiver operating characteristic curve (AUC) and compared with each other. Results The enrolled patients were split into training (n = 109) and validation sets (n = 47). A total of 806 features were extracted and the selected 10 optimal features were used in the construction of the radiomics model among the 707 stable features. The AUC of the nomogram model was 0.888 (95% CI: 0.762–0.961), which was superior to the clinical model (0.787, 95% CI: 0.643–0.893; p = 0.049) and comparable to the radiomics model (0.879, 95% CI: 0.751–0.965; p > 0.05). The nomogram model achieved a sensitivity of 90.5% and a specificity of 76.9% in the validation dataset. Conclusions The nomogram model could be considered as a noninvasive method to predict VPI with either highly sensitive or highly specific diagnoses depending on clinical needs.

There is a close relationship between potassium (K) and nitrogen (N). However, the roles of K under high N conditions remain unclear. Using a hydroponics approach, we monitored the morphological, physiological, and molecular changes in M9T337 apple (Malus domestica) rootstocks under different nitrate (10 and 30 mmol·L−1 NO3−) and K supply (0.5, 6, 10, and 20 mmol·L−1 K+) conditions. Results revealed that high nitrate inhibited the root growth of M9T337 rootstocks, downregulated the expressions of K transporter genes (MdPT5, MdHKT1, and MdATK1), and reduced the net NO3− and K+ influx at the surface of roots, thereby resulting in an N/K imbalance in rootstocks. Further investigation showed that 10 mmol·L−1 K increased the activity of N metabolic enzymes (NR, GS, NiR, and GOGAT), upregulated the expressions of genes related to nitrate uptake and transport (MdNRT1.1, MdNRT1.2, MdNRT1.5, and MdNRT2.4), promoted 15N transport from the roots to the shoots, optimized leaf N distribution, and improved photosynthetic N utilization efficiency under high nitrate conditions. These results suggest that the negative effects of high nitrate may be related to the N/K imbalance and that reducing N/K in plants by increasing K supply level can effectively alleviate the inhibition of N assimilation by high nitrate stress.

Elatostema is recognized as a taxonomically difficult group due to the reduced nature of the tiny flowers and inflorescences, also the large number of species (ca 650 to 700). Different opinions on morphological species delimitation have resulted in instability, which is problematic in such a speciose group. In this paper, the taxonomic status of three putative species, E. robustipes, E. scaposum, E. conduplicatum and their hypothetical closest relatives, was revised using morphological and molecular observations. Morphological comparison suggested high similarity between E. robustipes & E. retrohirtum, E. scaposum & E. oblongifolium, E. conduplicatum & E. coriaceifolium, respectively. Phylogenetic analyses of four universal DNA barcodes (ITS, trnH-psbA, matK and rbcL) suggested that each species pair represents a single evolutionary lineage. Taking these two findings together, we propose E. robustipes to be a synonym of E. retrohirtum, E. scaposum a synonym of E. oblongifolium, and E. conduplicatum a synonym of E. coriaceifolium. Our results recover the number, shape and size of the bracts and bracteoles to be relatively stable characters, and the disposition of the male inflorescences on modified stems to be an unstable character, unsuitable for species delimitation in Elatostema.

Abstract Background The association between chemotherapy-induced leukopenia (CIL) and survival for patients with early breast cancer (EBC) is not known. We investigated the relationship between different grades of CIL and survival in patients with EBC receiving adjuvant chemotherapy. Methods A total of 442 patients with EBC receiving a regimen containing an anthracycline (A) and taxane (T) were included into our analysis. Survival analyses were undertaken using Kaplan–Meier curves. The P-value was calculated using the log rank test. Subgroup analysis was conducted to investigate the correlation of CIL grade and survival based on the clinicopathological characteristics of patients. Afterwards, univariate and multivariate analyses screened out independent prognostic factors to construct a prognostic model, the robustness of which was verified. Results Patients with EBC who experienced grade 2–4 (“moderate” and “severe”) CIL were associated with longer overall survival (OS) than those with grade 0–1 (mild) CIL (P = 0.021). Compared with patients with mild CIL, OS was longer in patients with severe CIL (P = 0.029). Patients who suffered from moderate CIL tended to have longer OS than those with mild CIL (P = 0.082). Nevertheless, there was no distinguishable difference in OS between moderate- or severe-CIL groups. Subgroup analysis revealed that patients with moderate CIL had longer OS than those with mild CIL among patients who were premenstrual, or with human epidermal growth factor receptor 2-positive (HER2+), > 3 lymph nodes with metastases, a tumor diameter > 5 cm. A prognostic model based on menstrual status, N stage, and CIL grade showed satisfactory robustness. Conclusion The grade of CIL was strongly associated with the prognosis among patients with EBC who received a regimen containing both anthracyclines and taxanes. Patients with a “moderate” CIL grade tended to have better survival outcomes.

Abstract Background Changshun green-shell laying hens are unique to the Guizhou Province, China, and have high egg quality but relatively low yield. Egg production traits are regulated by the hypothalamus-pituitary-ovary axis. However, the underlying mechanism remains unclear. Thus, we conducted RNA sequencing of hypothalamic and pituitary tissues from low- and high-yielding Changshun green-shell laying hens to identify critical pathways and candidate genes involved in controlling the egg production rate. Results More than 39 million clean reads per sample were obtained, and more than 82% were mapped to the Gallus gallus genome. Further analysis identified 1,817 and 1,171 differentially expressed genes (DEGs) in the hypothalamus and pituitary, respectively. Nineteen DEGs were upregulated in both the hypothalamus and pituitary of high-yielding chickens. The functions of these DEGs were mainly associated with ion transport or signal transduction. Gene set enrichment analysis revealed that the pathways enriched in the hypothalamus were mainly associated with gonadotropin-releasing hormone (GnRH) secretion, neurotransmitter release, and circadian rhythms. The pathways enriched in the pituitary were mainly associated with GnRH secretion, energy metabolism, and signal transduction. Five and four DEGs in the hypothalamus and pituitary, respectively, were selected randomly for qRT-PCR analysis. The expression trends determined via qRT-PCR were consistent with the RNA-seq results. Conclusions The current study identified 19 DEGs upregulated in both the hypothalamus and pituitary gland, which could provide an important reference for further studies on the molecular mechanisms underlying egg production in Changshun green-shell laying hens. In addition, enrichment analysis showed that GnRH secretion and signal transduction, especially neurotransmitter release, play crucial roles in the regulation of egg production.

The assessment of disaster-causing hazards for the rainstorm event is a fundamental and key aspect of assessing the risk of rainstorm disasters, which can provide essential technical support for meteorological disaster prevention and mitigation. Using the hourly and daily precipitation data from 7 national meteorological observation stations and 120 regional automatic weather stations in Xiaogan City, as well as geographic information data, etc., a regional rainstorm event disaster-causing hazard that occurred in Xiaogan City on 12 August 2021 was evaluated base on dynamic assessment method of disaster hazard assessment of rainstorm process. By analyzing rainfall characteristic quantity, the disaster-causing factors were identified. Four disaster-causing factors were calculated using the information entropy-weight method, and the rainstorm event intensity index was calculated. The topographic-effected indices and the drainage-effected indices were determined as environmental factors based on analyzing the underlying surface characteristics in the rainstorm area. Then a synthetical index of disaster-prone environment was calculated using equal weighted summation of these indices. The disaster-causing hazard indices of the rainstorm event are composed of the weighted intensity indices of rainfall and the synthetical indices of disaster-prone environment. It was divided into five levels by using the Jenks natural breaks method, and the hazard level zonation chart for the rainstorm event was created using GIS. Finally, the hazard evaluation results were validated by the real rainstorm disaster data from the main affected area. The main results are as follows. (1) The "8.12" rainstorm event was characterized by its suddenness, heavy short-term rainfall, and concentrated precipitation, with 86.1% precipitation concentrated in 6 hours, and maximum precipitation in 6 hours of being up to a 50-year recurrence period, so the disaster-causing factors were selected by mainly considering the short-term precipitation. (2) The highest-level disaster hazard zones are located in most of Xiaonan district, central Yunmeng, north-east Yingcheng City, and southwest Anlu City, while the higher-level disaster hazard zone covers almost all the central part of Xiaogan City. Note that the results depend on the rainstorm intensity, the environment of the terrain, and the river network. (3) The highest- and higher-level hazard zones were areas corresponding to the regions with heavy rainstorm damage, with the actual disaster level reaching the "major" disaster level. The hazard assessment results actually reflected the actual losses in the main affected area.