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Root regeneration is an important factor influencing the healing rate of graft union and the survival of double-root-cutting grafting. To date, little information is available on how to enhance root regeneration of rootstock in grafted watermelon (Citrullus lanatus) seedlings. In this study, the effects of different light treatments on root regeneration were determined. This revealed that addition of far-red light (Fr) could significantly expedite root formation in the rootstock. Moreover, the results of transcriptome analysis revealed that plant hormone pathway and auxin-related genes were greatly induced by Fr, especially for auxin-response proteins (including CmIAA11, CmIAA17, and CmAUX28), Small auxin-up RNA genes (including CmSAUR20 and CmSAUR50) and the auxin efflux transporter (CmPIN3). In addition, the expression of Phytochrome Interacting Factor (PIFs), such as CmPIF1, CmPIF3 and CmPIF7, was remarkably increased by Fr. These genes may act together to activate auxin-related pathways under Fr treatment. Based on the results of HPLC-MS/MS analysis, the concentrations of different auxin-types in adventitious root were significantly influenced by Fr. Furthermore, the better growth of rootstock root displayed superior vasculature transport activity of the graft union with Fr treatment, which was determined by the acid magenta dyeing experiment. Therefore, all the results suggested that Fr could induce AR formation in rootstocks, which may be associated with the auxin accumulation by regulating the transcriptional level of auxin-related and PIF genes. The findings of this study demonstrated a practicable way to shorten the healing period of graftings and improve the quality of grafted watermelon seedlings, which will provide a theoretical basis for the speeding development of industrialized seedlings production.

Crowd-shipping, employing private drivers to partially replace company-owned trucks in distribution, has emerged as a prominent trend for its cost-effectiveness and sustainability. While crowd-shipping is known as a distribution pattern that combines economic efficiency and environmental benefits, however, the frequent occurrence of traffic congestion has made this pattern less effective than it should be. In this research, the problem of vehicle routing optimization under traffic congestion is investigated from the perspective of simultaneously reducing environmental pollution and costs. Considering private drivers picking up and delivering parcels on the way, this study incorporates the objective of minimizing transport as well as particulate matter (PM) and nitrogen oxides (NOx) emission costs into route optimization for crowd-shipping and proposes a Green Pickup and Delivery Problem with Private Drivers (GPDP-PD). To be more realistic, vehicle speeds depend on the level of traffic congestion, reflecting the time-dependent nature of the proposed model. An improved adaptive large neighborhood search (ALNS) algorithm is developed, and computational experiments are conducted to demonstrate the efficiency of the improved ALNS. Case studies show that there is uncertainty about the environmental benefits of crowd-shipping under traffic congestion. Our proposed model is capable of efficiently allocating private drivers and optimizing vehicle routes according to road conditions, thus identifying the crowd-shipping operational scheme with the lowest cost and emissions. Moreover, a time limit of 0.7-0.8 h and the low cost of private drivers can achieve environmental and economic benefits simultaneously. It provides useful insights into the sustainability of logistics and distribution.

Abstract Evaluate the real-world effectiveness and safety of different treatment regimens for treatment-naïve high viral load chronic hepatitis B (CHB) patients. Between January 2021 and August 2022, CHB patients with HBV DNA ≥ 107 IU/mL were collected from four medical centers in Shenzhen. Patients treated with mono or combine antiviral therapy. The primary endpoint was the cumulative incidence of virological response at 48 weeks, and other endpoints included changes in HBsAg, HBeAg, ALT, and eGFR at 48 weeks. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the bias. Weighted logistics regression was used to estimate the factors affecting virological response. A total of 391 patients were included in the study, with 296 patients undergoing statistical analysis after IPTW. The patients were distributed into four groups: ETV (n = 62), TDF (n = 89), TAF (n = 36), TDF + LdT/ETV (n = 109). The 48-week cumulative incidence of virological response was significantly lower in ETV group (52.3%) compared to TDF (71.7%), TAF (74.2%), and TDF + LdT/ETV groups (77.9%) (P

Abstract Oocyte aging is a key constraint on oocyte quality, leading to fertilization failure and abnormal embryonic development. In addition, it is likely to generate unfavorable assisted reproductive technology (ART) outcomes. SCM-198, a synthetic form of leonurine, was found to rescue the rate of oocyte fragmentation caused by postovulatory aging. Therefore, the aim of this study was to conduct a more in-depth investigation of SCM-198 by exploring its relationship with aged oocytes after ovulation or maternal aging and clarifying whether it affects cell quality. The results indicate that, compared to the postovulatory aged group, the 50 µM SCM-198 group significantly improved sperm-egg binding and increased fertilization of aged oocytes, restoring the spindle apparatus/chromosome structure, cortical granule distribution, and ovastacin and Juno protein distribution. The 50 µM SCM-198 group showed significantly normal mitochondrial distribution, low levels of reactive oxygen species (ROS), and a small quantity of early oocyte apoptosis compared to the postovulatory aged group. Above all, in vivo supplementation with SCM-198 effectively eliminated excess ROS and reduced the spindle/chromosome structural defects in aged mouse oocytes. In summary, these findings indicate that SCM-198 inhibits excessive oxidative stress in oocytes and alters oocyte quality both in vitro and in vivo. Graphical Abstract

Abstract This study aimed to investigate the knowledge, attitude, and practice (KAP) of non-emergency surgical patients toward anesthesia. This cross-sectional study was conducted between May and October 2023 at Zibo Central Hospital among non-emergency surgical patients. A total of 429 valid questionnaires were enrolled (mean age: 42.81 ± 13.17 years old; 227 (52.91%) females). The mean KAP scores were 7.79 ± 3.95 (possible range: 0–18), 32.35 ± 2.80 (possible range: 8–40), and 18.14 ± 3.96 (possible range: 6–24), respectively. Multivariate logistic regression analysis showed that knowledge (OR = 1.095, 95% CI 1.036–1.158, P = 0.001) and previous poor anesthesia experience (OR = 0.081, 95% CI 0.017–0.386, P = 0.002) were independently associated with practice. Non-emergency surgical patients had inadequate knowledge, positive attitude, and proactive practice towards anesthesia. It is crucial for healthcare professionals to implement targeted educational interventions to inform patients about the anesthesia process, potential risks, and benefits.

ObjectiveRetroperitoneal fibrosis (RPF) is a rare disease characterized by the presence of fibroinflammatory tissue that surrounds the abdominal aorta and the iliac arteries and often entraps the ureters. Hydronephrosis is a common complication of RPF, however, its clinical features and outcomes have not been well elucidated.MethodsA total of 115 RPF-related hydronephrosis patients have been recruited from 9 clinical centers in China since March 2010. They were followed up until death or September 2021, whichever came first.ResultsThe mean age at diagnosis was 58.83 ± 12.13 years, and 80 patients (69.57%) were men. The median disease duration was 3.00 (1.00, 9.00) months. Renal impairment was observed in 88.35% of the patients, and 49.57% showed bilateral ureteral involvement. Elevated ESR and CRP were presented in 80.28 and 62.02% of the patients, respectively. Overall, 28.21% (11/39) of the patients had increased IgG4 levels, and 41.38% (12/29) showed positive pathological IgG4 staining (IgG4+/IgG+ ≥ 40% or IgG4+ ≥ 10/HPF). Among them, three patients were diagnosed as IgG4RD. After 60.43 ± 34.53 months of follow-up, 36 patients had poor prognosis, which was associated with severe kidney impairment, bilateral hydronephrosis and inflammation status (elevated ESR and IgG) at diagnosis by case–control study. eGFR and creatinine were independent risk factors after adjusting for all other significant associations (p = 0.002 and p = 0.067, respectively). Glucocorticoid-based therapy could reduce the time of stenting, decrease the need for long-term ureteral stenting/percutaneous nephrostomy (PNS)/ureterolysis, increase the rate of mass shrinkage, and reduce the new requirement of hemodialysis compared to surgery-only strategy for RPF-related hydronephrosis patients in need of renal drainage, but did not reduce new-onset renal atrophy.ConclusionSeverity of kidney dysfunction and inflammation status were related to the poor prognosis of hydronephrosis induced by RPF. More efficient interventions and strategies are needed to further improve outcomes.

Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with a combination of aspirin and a potent P2Y12 receptor inhibitor. However, the potential benefits of aspirin were partially constrained by the intolerance of some patients. The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.This retrospective study was conducted at a single center and utilized propensity score matching. The enrollment spanned from January 2019 to June 2022, incorporating patients with AMI after PCI. The participants were categorized into two groups based on discharged prescriptions: the aspirin DAPT group and the indobufen DAPT group. The primary endpoint focused on net adverse clinical event (NACE), defined as a composite outcome, including cardiac death, recurrence of MI, definite or probable stent thrombosis (ST), target lesion revascularization (TLR), ischemic stroke and Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5. All the patients underwent a one-year follow-up period.A total of 1451 patients were enrolled in this study, with 258 assigned to the indobufen DAPT group and 1193 to the aspirin DAPT group. Following 1:1 propensity score matching, 224 patients were retained in each group. In the indobufen DAPT group, 58 individuals (25.9%) experienced the primary endpoint within one year, compared to 52 individuals (23.2%) in the aspirin DAPT group (HR 1.128, 95% CI 0.776–1.639, p = .527). Specifically, no significant differences were observed in either the efficacy endpoint (MACCE, 20.1% vs. 14.7%, HR 1.392, 95% CI 0.893–2.170, p = .146) or the safety endpoint (BARC 2,3 or 5, 8.04% vs. 10.30%, HR 0.779, p = .427). These findings remained consistent at 1, 3, or 6 months. Additionally, the incidence of gastrointestinal symptoms were significantly lower in indobufen DAPT group compared to the aspirin DAPT group (7.1% vs. 14.3%, p = .022).Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.

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.

In vertical farms, the supplementation of far-red light has been widely applied to regulate plant growth and development. However, the relative contribution of far-red to photosynthesis and plant growth in indoor production systems is not sufficiently quantified. This study quantify the photosynthesis and growth responses under different levels of supplemental far-red in lettuce using a 3D modelling approach. Lettuce were cultivated under either white light or red to far-red (R:FR) ratio of 1.6 or 0.8. Measurements of plant morphological traits, leaf photosynthesis, and organ fresh and dry mass were taken and the 3D modelling approach was used to simulate plant photosynthesis and biomass accumulation. Results showed that leaf elevation angle, leaf expansion rate, and plant height significantly increased at each growth stage as the R:FR ratio decreased. Far-red light also promoted plant growth, leading to an increase in the dry and fresh weight of lettuce throughout the entire growth period. However, plants cultivated at low R:FR showed reduced maximum Rubisco carboxylation rate and maximum electron transport rate, which indicated that far-red light reduced the photosynthetic capacity in lettuce. Nevertheless, 3D model simulations demonstrated that plants exposed to enhanced far-red light exhibited increased light interception and whole-plant photosynthesis. The integrated analysis of photosynthetic parameters and plant morphological changes on the photosynthetic rate of the whole plant indicated that the positive effects of plant morphological changes outweighed the negative impacts of photosynthetic parameters. These results implied that far-red light-induced morphological changes enhanced light interception and whole-plant photosynthesis, thereby increased lettuce yield.

Introduction Maintaining haemodynamic stability is crucial but challenging during the induction and maintenance of general anaesthesia (GA) in patients undergoing off-pump coronary artery bypass grafting (OPCABG). Remimazolam tosylate is a novel ultra-short-acting benzodiazepine with minimal cardiovascular depression. Currently, non-inferior studies comparing the haemodynamic changes induced by remimazolam and etomidate are limited. This study aims to assess the efficacy and safety of remimazolam tosylate for the induction and maintenance of GA in patients undergoing OPCABG.Method and analysis This two-armed non-inferiority randomised controlled trial will include 88 patients aged 18–75 years who are scheduled for OPCABG. Patients will be randomly assigned in a 1:1 ratio to receive either remimazolam tosylate or etomidate and propofol for anaesthesia induction and maintenance. The primary outcome will be the fluctuation of mean artery pressure during anaesthesia induction. Secondary outcomes will include adverse events, adverse drug reactions, the cumulative dosage of vasoactive drugs, vital signs and bispectral index values at different time points, lengths of postoperative mechanical ventilation and tracheal intubation, lengths of intensive care unit stay and hospital stay and hospital mortality. Analyses will be conducted using both the intention-to-treat approach and the per-protocol approach.Ethics and dissemination This study was approved by the Ethics Committee of Zibo Central Hospital (No. 2024001). The trial results will be submitted to an international peer-reviewed journal.Trial registration number ChiCTR.gov.cn: ChiCTR2400079615.

Introduction Helicobacter pylori is a type of Gram-negative microaerobic bacteria that inhabits the gastric mucosal epithelium. It can cause various gastrointestinal diseases including gastritis, peptic ulcer and gastric cancer. White blood cells (WBC) are common immune cells, the increase in whose countoften indicates the presence of an infection. Currently, the relationship between H. pylori and WBC count remains full of controversy. This study aims to further elucidate the effects of H. pylori on WBC count in a population undergoing physical examination.Methods and analysis A total of 864 participants who underwent physical examination and 14C urea breath test (UBT) were retrospectively enrolled in this study from January to June 2021. The overall population was divided into H. pylori-negative (Hp−) and H. pylori-positive (Hp+) groups based on the disintegration per minute (DPM) value detected by UBT. Spearman’s correlation analysis was used to assess the correlation between DPM and WBC count. General linear regression models were applied to assess the potential factors contributing to the increase in WBC count. Generalised additive model (GAM) was performed to identify the non-linear relationship between DPM and WBC count. Additionally, a piecewise linear regression was used to examine the threshold effect of the DPM on WBC count.Results 403 subjects were diagnosed with H. pylori infection. The WBC and platelet (PLT) counts in the Hp+ group were significantly higher than those in the Hp− group. Additionally, the prevalence of H. pylori infection gradually increased with the WBC count quartiles (38.89% and 54.67% in quartile 1 and quartile 4, respectively). Spearman’s correlation analysis showed that the DPM value significantly correlated with WBC count (r=0.089, p=0.009) and PLT count (r=0.082, p=0.017). The linear model revealed a positive independent association of H. pylori infection and DPM with WBC count (βHp+=0.398 (95% CI 0.170, 0.625), p155 (βDPM=−0.005 (95% CI −0.017, 0.007), p=0.423; βDPM=0.006 (95% CI 0.002, 0.013), p=0.047; and βDPM=−0.007 (95% CI −0.012, –0.002), p=0.004, respectively).Conclusions H. pylori infection was independently and positively correlated with WBC count; however, the effect of DPM on WBC count varied across different WBC count intervals, suggesting distinct immunological responses at different stages of infection.

Objective: This study explores the mechanism of AAC in intervening heart failure (HF) using network pharmacology, molecular docking, and in vitro experimental validation. Methods: The “active component-target” network and the “drug-disease target” protein interaction network were constructed using Cytoscape 3.9.0 and STRING Database. GO and KEGG enrichment analysis was performed using DAVID database. Then, the molecular docking of major compounds and target proteins was carried out using Autodock 1.5.7, and visualized with PyMOL 2.4.0 software. Finally, in vitro experimental validation was performed to explore the potential targets of AAC in treating HF. Results: The study revealed significant targets implicated in a variety of GO bioprocess programs and KEGG signaling networks. The primary chemicals to have strong binding ability with target proteins in molecular docking, with quercetin having the best binding energy with MAPK at −6.72 Kcal/Mol.Validation of cellular experiments showed that AAC might reduce the apoptosis that doxorubicin causes in AC16 cells by controlling the levels of PIK3CA, AKT1, and MAPK1. Conclusion: This study preliminarily reveals that AAC can treat HF through multiple components and multiple targets by using network pharmacology, molecular docking, and experimental validation.

To investigate the effects of various types of farmland shelterbelts on soil quality and soil bacterial community diversity, this study focused on soil samples from four different shelterbelt types in the Alaer reclamation area, including Populus euphratica Oliv.- Populus tomentosa Carrière (PP), Elaeagnus angustifolia L.- Populus euphratica Oliv. (EP), Populus alba var. pyramidalis Bunge (P), and Salix babylonica L. (S). We analyzed their physical, chemical, biological properties as well as the differences in bacterial community structure, and explored the influencing factors on soil microbial community characteristics through microbial correlation network analysis. The results showed that: (1) There were significant differences in soil properties among the four types of farmland shelterbelts (p < 0.05), with P soils exhibiting the highest levels of organic matter, total nitrogen, and total phosphorus contents. (2) The Alpha diversity indices of soil bacteria showed significant differences among the four types of farmland shelterbelts (p < 0.05), with the P soils displayed the highest Chao1 and Shannon indices. (3) There were differences in the composition and abundance of dominant soil bacterial communities among different farmland shelterbelts, notably, the abundances of Verrucomicrobia, Acidobacteria, and Planctomycetes were significantly higher in P soils compared to the other three types. (4) The complexity of the correlation network between microbial species and environmental factors was highest in EP soils, soil microbial biomass nitrogen and available phosphorus were the main influencing factors. These findings indicated that different types of farmland shelterbelts had significant impacts on soil properties and soil bacterial communities. Soil bacterial communities were regulated by soil properties, their changes reflected a combined effect of soil characteristics and tree species.

Antimony (Sb) is a metalloid, widely presents in the environment and associates with human health. In this study, we aimed to decipher whether Sb exposure is harmful to female reproduction and explore the underlying mechanisms. The ICR mice were exposed to 0, 5, 10, and 20 mg/kg acetate potassium Sb tartrate trihydrate by intraperitoneal injection for 10 days, then mouse oocytes were collected for further analysis. We first found a significant decrease in the proportion of MII-stage oocytes obtained from supernumerary ovulation in the fallopian tubes and early embryo development under Sb treatment. Then a series of tests showed Sb affects oocyte maturation by damaging the cytoskeleton of microtubule and actin. Moreover, the abnormal distribution of cortical granules and their component Ovastacin in oocytes, combined with reduced expression levels of Juno, affected sperm-oocyte binding and led to fertilization failure. Based on the sequencing results and experimental validation, it was demonstrated that Sb exposure impairs mitochondrial distribution and membrane potential, elevated levels of mitochondrial superoxide, finally caused energy supply deficits. Mitochondrial damage in oocytes after Sb exposure results in the excessive oxidative stress and early apoptosis. Taken together, these data suggest that Sb exposure decreases oocyte quality and female fertilization ability by impairing mitochondrial function and redox perturbation.

Abstract Previous studies have reported associations between newly diagnosed diabetes and poor outcomes after percutaneous coronary intervention (PCI), but there is limited data focusing on elderly patients (age ≥ 65). This study aimed to analyze the prevalence and clinical implications of newly diagnosed diabetes in elderly patients who underwent PCI. From 2004 to 2021, a total of 2456 elderly patients who underwent invasive PCI at Korea University Guro Hospital were prospectively enrolled and followed up for a median of five years. The primary endpoint was five-year major adverse cardiovascular events (MACE). Cox regression was used to evaluate whether newly diagnosed diabetes impacted on long-term clinical outcomes. Newly diagnosed diabetes was presented in approximately 8.1% to 10.9% of elderly patients who underwent PCI. Those who had a new diagnosis of diabetes had a higher risk of MACE than previously known diabetes (25.28% vs. 19.15%, p = 0.039). After adjusting for significant factors, newly diagnosed diabetes remained an independent predictor of MACE (HR [hazard ratio] 1.64, 95% confidence interval [CI] 1.24–2.17, p

Abstract Multiple sevoflurane exposures may damage the developing brain. The neuroprotective function of dexmedetomidine has been widely confirmed in animal experiments and human studies. However, the effect of dexmedetomidine on the glymphatic system has not been clearly studied. We hypothesized that dexmedetomidine could alleviate sevoflurane-induced circulatory dysfunction of the glymphatic system in young mice. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 2 h daily, continuously for 3 days. Intraperitoneal injection of either normal saline or dexmedetomidine was administered before every anaesthesia. Meanwhile the circulatory function of glymphatic system was detected by tracer injection at P8 and P32. On P30-P32, behavior tests including open field test, novel object recognition test, and Y-maze test were conducted. Primary astrocyte cultures were established and treated with the PI3K activator 740Y-P, dexmedetomidine, and small interfering RNA (siRNA) to silence ΔFosB. We propose for the first time that multiple exposure to sevoflurane induces circulatory dysfunction of the glymphatic system in young mice. Dexmedetomidine improves the circulatory capacity of the glymphatic system in young mice following repeated exposure to sevoflurane through the PI3K/AKT/ΔFosB/AQP4 signaling pathway, and enhances their long-term learning and working memory abilities.

Abstract Background Triple-negative breast cancer (TNBC) is recognized as the most aggressive and immunologically infiltrated subtype of breast cancer. A high circulating neutrophil-to-lymphocyte ratio (NLR) is strongly linked to a poor prognosis among patients with breast cancer, emphasizing the critical role of neutrophils. Although the involvement of neutrophils in tumor metastasis is well documented, their interactions with primary tumors and tumor cells are not yet fully understood. Methods Clinical data were analyzed to investigate the role of neutrophils in breast cancer. In vivo mouse model and in vitro co-culture system were used for mechanism researches. Blocking experiments were further performed to identify therapeutic agents against TNBC. Results TNBC cells secreted GM-CSF to sustain the survival of mature neutrophils and upregulated CD11b expression. Through CD11b, neutrophils specifically binded to ICAM1 on TNBC cells, facilitating adhesion. Transcriptomic sequencing combined with human and murine functional experiments revealed that neutrophils, through direct CD11b-ICAM1 interactions, activated the MAPK signaling pathway in TNBC cells, thereby enhancing tumor cell invasion and migration. Atorvastatin effectively inhibited ICAM1 expression in tumor cells, and tumor cells with ICAM1 knockout or treated with atorvastatin were unresponsive to neutrophil activation. The MAPK pathway and MMP9 expression were significantly inhibited in the tumor tissues of TNBC patients treated with atorvastatin. Conclusions Targeting CD11b-ICAM1 with atorvastatin represented a potential clinical approach to reduce the malignant characteristics of TNBC. Graphical Abstract

Abstract Fetal adenocarcinoma of the lung (FLAC) is a rare form of lung adenocarcinoma and was divided into high-grade (H-FLAC) and low-grade (L-FLAC) subtypes. Despite the existence of some small case series studies, a comprehensive multi-omics study of FLAC has yet to be undertaken. In this study, we depicted the multi-omics landscapes of this rare lung cancer type by performing multi-regional sampling on 20 FLAC cases. A comparison of multi-omics profiles revealed significant differences between H-FLAC and L-FLAC in a multi-omic landscape. Two subtypes also showed distinct relationships between multi-layer intratumor heterogeneity (ITH). We discovered that a lower genetic ITH was significantly associated with worse recurrence-free survival and overall survival in FLAC patients, whereas higher methylation ITH in H-FLAC patients suggested a short survival. Our findings highlight the complex interplay between genetic and transcriptional heterogeneity in FLAC and suggest that different types of ITH may have distinct implications for patient prognosis.

Abstract Background Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality. Methods We collected a prospective study cohort of 110 stage I–II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation. Results Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942–0.982) in the study cohort, 0.972 (95% CI: 0.953–0.992) in the first validation cohort and 0.937 (95% CI: 0.890–0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified. Conclusions We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer. Trial registration This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.

Genetic factors play significant roles in the tumorigenicity of lung cancer; however, there is lack of systematic and large‐scale characterization of pathogenic germline variants for lung cancer. In this study, germline variants in 146 preselected cancer‐susceptibility genes were detected in 17 904 Chinese lung cancer patients by clinical next‐generation sequencing. Among 17 904 patients, 1738 patients (9.7%) carried 1840 pathogenic/likely pathogenic (P/LP) variants from 87 cancer‐susceptibility genes. SBDS (SBDS ribosome maturation factor) (1.37%), TSHR (thyroid stimulating hormone receptor) (1.20%), BLM (BLM RecQ like helicase) (0.62%), BRCA2 (BRCA2 DNA repair associated) (0.62%), and ATM (ATM serine/threonine kinase) (0.45%) were the top five genes with the highest overall prevalence. The top mutated pathways were all involved in DNA damage repair (DDR). Case–control analysis showed SBDS c.184A>T(p.K62*), TSHR c.1574T>C(p.F525S), BRIP1 (BRCA1 interacting helicase 1) c.1018C>T(p.L340F), and MUTYH (mutY DNA glycosylase) c.55C>T(p.R19*) were significantly associated with increased lung cancer risk (q value

Summary: Background: The standard malaria rapid diagnostic test (RDT) and newer ultra-sensitive RDT (uRDT) target Plasmodium falciparum histidine rich protein-2 (HRP2), which persists post-treatment. The duration of test positivity has not previously been studied in a low transmission setting. Methods: We conducted a longitudinal cohort study in a low transmission setting in Namibia. RDT-positive individuals identified through passive and active case detection were treated and followed weekly for testing by RDT and uRDT, HRP2 quantification, quantitative PCR (qPCR) of parasitemia, and quantitative reverse transcriptase PCR (RT-PCR) of gametocytemia, until RDT and uRDT were negative for two consecutive weeks. Determinants of persistent positivity were identified using Cox proportional hazards models. Findings: Among 137 participants with complete follow-up and no evidence of resurgence during follow-up, median duration of positivity was 42 days (range: 3−98 range) for RDT, compared to 67 days (range 12–105) for uRDT. In a sub-analysis of those with laboratory data before treatment (n = 60), drug resistance did not explain persistent positivity. Younger age (

Background The severity of acute gastrointestinal injury (AGI) is a critical determinant of survival in sepsis. However, there is no specifically interventional management for gastrointestinal dysfunction. Toll-like Receptor 4 (TLR4) is an important contributor to sepsis-induced multiple organ dysfunction syndrome. So, we investigated the effect of TLR4 on leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) + cells and goblet cells and its potential mechanism. Methods A cecal ligation and puncture (CLP) model reflecting the development of clinical sepsis was developed. Tak-242, a TLR4 inhibitor, was administered to septic rats at a dose of 3 mg/kg via intraperitoneal injection. Immunohistochemistry was performed to detect TLR4 and Lgr5+ cells. AB-PAS staining was performed to detect goblet cells. MUC1 and MUC2 secreted by goblet cells, biomarkers of endoplasmic reticulum (ER) stress and inflammatory cytokines in the intestine were detected by western blotting and real-time PCR. Results We found that the upregulation of the TLR4/NF-κB signaling pathway activated intestinal inflammatory response in sepsis. Meanwhile, the structure of intestinal mucosa was destroyed, Lgr5+ cells and goblet cells count were significantly reduced, and the secretory function of goblet cells also decreased. Further studies have found that TLR4 increased the levels of activating transcription factor-6 (ATF6), XBP1, ER chaperone (Bip) and CHOP, but did not activate the protein kinase RNA (PKR)-like ER kinase (P-PERK). Conclusion We concluded that the inhibition of TLR4/NF-κB signaling pathway can reduce intestinal inflammatory response, protect intestinal mucosa, protect Lgr5+ cells, goblet cells and relieve ER stress. Our findings suggest that Tak-242 protects Lgr5+ cells and goblet cells after sepsis, partly may be through the suppression of ER stress. Thus, inhibition of TLR4-mediated ER stress may be a promising therapy of septic AGI.

Abstract Avoiding the tedious process of crystal cultivation and directly obtaining organic crystals with desirable phosphorescent performance is of great significance for studying their structure and properties. Herein, a set of benzophenone‐cored phosphors with bright green afterglow are obtained on a large scale through in‐situ generation via an end‐capping strategy to suppress non‐radiative triplet excitons and reinforce the intermolecular interactions. The ordered arrangement of phosphors with alkyl‐cyano groups as regulators is crucial for the enhancement of room‐temperature phosphorescence (RTP) emission, which has been further verified by the attenuated lifetimes in isolated states through the formation of inclusion complexes upon binding with pillar[5]arenes. Moreover, the hierarchical interactions of phosphors, including hydrogen bonding, π‐π stacking interactions, and van der Waals forces, are quantified by crystal structures and theoretical calculation to deeply interpret the origins of RTP emission. With this study, we provide a potential strategy for the direct acquisition of crystalline organic phosphors and modulation of RTP.

Introduction: Gouty nephropathy (GN) arises from factors like excessive purine intake, metabolic disorders or abnormal synthesis, and uric acid hypersaturation in the blood, leading to urate crystal deposition in kidney tissue. DaiTongXiao (DTX) is a remedy used by the Dai people of China. It shows efficacy in lowering uric acid levels and exhibits anti-inflammatory and kidney-protective properties.Methods: A GN rat model was induced using adenine and potassium oxonate. Following DTX administration, various parameters were assessed in urine, serum, and kidney tissue. Western blot analysis evaluated TLR4/MyD88/NF-κB signaling proteins, while immunofluorescence examined NF-κB nuclear expression.Results: DTX treatment improved kidney morphology, increased body weight, and kidney index and enhanced urinary levels of blood urea nitrogen (Bun), 24-h urinary protein, uric acid (UA), and allantoin in GN rats, reducing UA, Bun, creatinine (Cre), cystatin C (CysC), serum amyloid A (SAA), α1-microglobulin (MG), and β2-MG in serum analysis. Renal tissue assessments showed decreased xanthine oxidase (XOD), hydroxyproline (Hyp), α-smooth muscle actin (α-SMA), and collage type Ⅳ (COL-Ⅳ). Kidney damage severity was notably reduced. DTX lowered serum inflammatory factors like interleukin (IL) −18, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), transforming growth factor-β1 (TGF-β1), and IL-1β in the rat serum, reducing chemokine monocyte chemoattractant protein-1 (MCP-1) and adhesion factor vascular cell adhesion molecule-1(VCAM-1). Western blotting demonstrated the downregulation of TLR4/MyD88/NF-κB pathway proteins, and immunofluorescence revealed reduced NF-κB expression in renal tissue.Discussion: DTX exhibits significant anti-GN effects by modulating TLR4/MyD88/ NF-κB pathway protein expression, reducing inflammatory factor release, and inhibiting GN progression.

Accurate haplotyping facilitates distinguishing allele-specific expression, identifying cis-regulatory elements, and characterizing genomic variations, which enables more precise investigations into the relationship between genotype and phenotype. Recent advances in third-generation single-molecule long read and synthetic co-barcoded read sequencing techniques have harnessed long-range information to simplify the assembly graph and improve assembly genomic sequence. However, it remains methodologically challenging to reconstruct the complete haplotypes due to high sequencing error rates of long reads and limited capturing efficiency of co-barcoded reads. We here present a pipeline, AsmMix, for generating both contiguous and accurate diploid genomes. It first assembles co-barcoded reads to generate accurate haplotype-resolved assemblies that may contain many gaps, while the long-read assembly is contiguous but susceptible to errors. Then two assembly sets are integrated into haplotype-resolved assemblies with reduced misassembles. Through extensive evaluation on multiple synthetic datasets, AsmMix consistently demonstrates high precision and recall rates for haplotyping across diverse sequencing platforms, coverage depths, read lengths, and read accuracies, significantly outperforming other existing tools in the field. Furthermore, we validate the effectiveness of our pipeline using a human whole genome dataset (HG002), and produce highly contiguous, accurate, and haplotype-resolved assemblies. These assemblies are evaluated using the GIAB benchmarks, confirming the accuracy of variant calling. Our results demonstrate that AsmMix offers a straightforward yet highly efficient approach that effectively leverages both long reads and co-barcoded reads for haplotype-resolved assembly.

Continued population growth and limited land availability will facilitate the utilization of plant growth regulators (PGRs) in sustainable agriculture to enhance crop yields. The PGRs industry has progressed significantly from 2003 to 2022, resulting in a surge of research activities in the field of PGRs. However, the existing studies lack the exploration of the industry trends, as well as the challenges and opportunities for innovation in PGR development. Here, we analyze the dynamic trends within the PGR industry by examining key factors such as the PGR market, patent applications, scientific papers, and PGRs registrations from 2003 to 2022. Additionally, we investigate the specific effects of major agrochemicals on plants. These data will provide essential insights into the ongoing evolution and future trends of PGRs. Importantly, it is crucial to actively pursue research and development (R&D) of a broader range of PGRs to respond to the current needs of the PGR market and drive further growth therein.

Particulate matter (PM), usually formed as aerosols suspended in atmosphere, is becoming a carrier of viruses and bacteria, accelerating the spread of respiratory diseases. Hence, air filtration devices are widely utilized for removing PM. In this study, a regenerated cellulose (RC) film was prepared with the properties of good mechanical strength, antibacterial, and highly efficient filtration (EF) properties, through cellulose dissolution and further crosslinking with P(AGE-DMDAAC)/ZnO. Results exhibited that the Young's modulus of the composite membrane was nearly 4.3 GPa. Additionally, the antibacterial performance against Escherichia coli and Staphylococcus aureus, was up to 99.89% and 99.67%, respectively. Meanwhile, RC composite filter exhibited a high PM 2.5 capture efficiency (over 99.91%). This study introduces an interesting approach to produce antibacterial films with the characteristics of notably good mechanical performance and high fine particle EF that can be utilized in a high humidity environment.

Abstract Objectives In the current study, for the first time, we reported a novel HCV molecular diagnostic approach termed reverse transcription loop-mediated isothermal amplification integrated with a gold nanoparticles-based lateral flow biosensor (RT-LAMP-AuNPs-LFB), which we developed for rapid, sensitive, specific, simple, and visual identification of HCV. Methods A set of LAMP primer was designed according to 5’untranslated region (5’UTR) gene from the major HCV genotypes 1b, 2a, 3b, 6a, and 3a, which are prevalent in China. The HCV-RT-LAMP-AuNPs-LFB assay conditions, including HCV-RT-LAMP reaction temperature and time were optimized. The sensitivity, specificity, and selectivity of our assay were evaluated in the current study. The feasibility of HCV-RT-LAMP-AuNPs-LFB was confirmed through clinical serum samples from patients with suspected HCV infections. Results An unique set of HCV-RT-LAMP primers were successfully designed targeting on the 5’UTR gene. The optimal detection process, including crude nucleic acid extraction (approximately 5 min), RT-LAMP reaction (67℃, 30 min), and visual interpretation of AuNPs-LFB results (~ 2 min), could be performed within 40 min without specific instruments. The limit of detection was determined to be 20 copies per test. The HCV-RT-LAMP-AuNPs-LFB assay exhibited high specificity and anti-interference. Conclusions These preliminary results confirmed that the HCV-RT-LAMP-AuNPs-LFB assay is a sensitive, specific, rapid, visual, and cost-saving assay for identification of HCV. This diagnostic approach has great potential value for point-of-care (POC) diagnostic of HCV, especially in resource-challenged regions.

Abstract The present study provides a systematic review of prosody research in linguistic journals through a bibliometric analysis. Using the bibliographic data from 2001 to 2021 in key linguistic journals that publish prosody-related research, this study adopted co-citation analysis and keyword analysis to investigate the state of the intellectual structure and the emerging trends of research on prosody in linguistics over the past 21 years. Additionally, this study identified the highly cited authors, articles and journals in the field of prosody. The results offer a better understanding of how research in this area has evolved and where the boundaries of prosody research might be pushed in the future.

Objective The aim of this study was to investigate the effect of geriatric training integrated with ideological and political education on the processing ability of standardized training for resident physicians to cultivate the physician-patient relationship. Methods From September 2019 to June 2022,a total of 40 cases at Geriatrics Training Base of the First Hospital of Jilin University were selected,including 19 males and 21 females.Before and after training,DDPQR-10 questionnaire was used to investigate,and then to evaluate the effect of standardized training of geriatrics integrating ideological education on the processing ability of the physician-patient relationship of geriatrics. Results After standardized training,the bed management ability of standardized training students and the proportion of standardized training students who obtained the qualification certificate of doctors were significantly increased,all P

Small-scale pedestrian detection is one of the challenges in general object detection. Factors such as complex backgrounds, long distances, and low-light conditions make the image features of small-scale pedestrians less distinct, further increasing the difficulty of detection. To address these challenges, an Enhanced Feature-Fusion YOLO network (EFF-YOLO) for small-scale pedestrian detection is proposed. Specifically, this method employs a backbone based on the FasterNet block within YOLOv8n, which is designed to enhance the extraction of spatial features while reducing redundant operation. Furthermore, the gather-and-distribute (GD) mechanism is integrated into the neck of the network to realize the aggregation and distribution of global information and multi-level features. This not only strengthens the faint features of small-scale pedestrians but also effectively suppresses complex background information, thereby improving the accuracy of small-scale pedestrians. Experimental results indicate that EFF-YOLO achieves detection accuracies of 72.5%, 72.3%, and 91% on the three public datasets COCO-person, CityPersons, and LLVIP, respectively. Moreover, the proposed method reaches a detection speed of 50.7 fps for 1920 × 1080-pixel video streams on the edge device Jetson Orin NX, marking a 15.2% improvement over the baseline network. Thus, the proposed EFF-YOLO method not only boasts high detection accuracy but also demonstrates excellent real-time performance on edge devices.

Abstract Objective We analyzed the influence of the location of the upper and lower cement on the sandwich vertebrae (SV) by computer finite element analysis. Materials and Methods A finite element model of the spinal segment of T11‐L1 was constructed and 6 mL of cement was built into T11 and L1 simultaneously. According to the various distributions of bone cement at T11 and L1, the following four groups were formed: (i) Group B‐B: bilateral bone cement reinforcement in both T11 and L1 vertebral bodies; (ii) Group L‐B: left unilateral reinforcement in T11 and bilateral reinforcement in L1; (iii) Group L‐R: unilateral cement reinforcement in both T11 and L1 (cross); (iv) Group L‐L: unilateral cement reinforcement in both T11 and L1 (ipsilateral side). The maximum von Mises stress (VMS) and maximum displacement of the SV and intervertebral discs were compared and analyzed. Results The maximum VMS of T12 was in the order of size: group B‐B

Summary: Increased cases of sepsis during COVID-19 in the absence of known bacterial pathogens highlighted role of viruses as causative agents of sepsis. In this study, we investigated clinical, laboratory, proteomic, and metabolomic characteristics of viral sepsis patients (n = 45) and compared them to non-sepsis patients with COVID-19 (n = 186) to identify molecular mechanisms underlying the pathology of viral sepsis in COVID-19. We identified unique metabolomic and proteomic signatures that suggest a substantial perturbation in the coagulation, complement, and platelet activation pathways in viral sepsis. Our proteomic data indicated elevated coagulation pathway protein (fibrinogen), whereas a decrease in many of the complement proteins was observed. These alterations were associated with the functional consequences such as susceptibility to secondary bacterial infections and potentially contributing to both local and systemic disease phenotypes. Our data provide novel aspect of COVID-19 pathology that is centered around presence of sepsis phenotype in COVID-19.

This paper reports a mini-resonant photoacoustic sensor for high-sensitivity trace gas sensing. The sensor primarily contains a sphere-cylinder coupled acoustic resonator, a cylindrical buffer chamber, and a fiber-optic acoustic sensor. The acoustic field distributions of this mini-resonant photoacoustic sensor and the conventional T-type resonant photoacoustic sensor have been carefully evaluated, showing that the first-order resonance frequency of the present mini-resonant photoacoustic sensor is reduced by nearly a half compared to that of the T-type resonant photoacoustic sensor. The volume of the developed photoacoustic cavity is only about 0.8 cm3. Trace methane is selected as the target analytical gas and a detection limit of 101 parts-per-billion at 100-s integration time has been achieved, corresponding to a normalized noise equivalent absorption (NNEA) coefficient of 1.04 × 10−8 W·cm−1·Hz−1/2. The developed mini-resonant photoacoustic sensor provides potential for high-sensitivity trace gas sensing in narrow spaces.