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Abstract Background Heat stress (HS) commonly occurring in summer has gradually become a factor threatening the reproductive performance of male dairy goats by reducing their fecundity. Despite the melatonin is applied to relieve HS, it is still unclear whether melatonin protects against reproductive damage induced by HS in dairy goats and how it works. The purpose of the present study is to evaluate the role of melatonin in alleviating HS-induced spermatogenesis dysfunction in male dairy goats and further explore its mechanism. Results HS impaired spermatogenesis, sperm formation in the testes, and sperm maturation in the epididymis of dairy goats, resulting in decreased sperm quality. Melatonin rescued the decrease of sperm quality induced by HS via decreasing inflammatory and oxidative stress levels in testicular tissue and enhancing intercellular barrier function within the testes. Amplicon-based microbiota analysis revealed that despite gut microbiota differences between melatonin-treated dairy goats and NC dairy goats to some extent, melatonin administration tends to return the gut microbiota of male dairy goats under HS to the levels of natural control dairy goats. To explore whether the protective role of melatonin in sperm quality is mediated by regulating gut microbiota, fecal microbiota of HS dairy goats with or without melatonin treatment were transferred to HS mice, respectively. We found HS mice that had received fecal bacteria of HS dairy goats experienced serious testicular injury and dyszoospermia, while this phenomenon was ameliorated in HS mice that had received fecal bacteria of dairy goats treated with melatonin, indicating melatonin alleviates HS-induced spermatogenic damage in a microbiota dependent manner. We further found that the testicular tissue of both HS dairy goats and mice transplanted with HS dairy goat feces produced large amounts of arachidonic acid (AA)-related metabolites, which were closely associated with semen quality. Consistently, supplementation with AA has been shown to elevate the levels of inflammation and oxidative stress in the testicular tissue of mice, disrupting intercellular connections and ultimately leading to spermatogenic disorders. Conclusion This study has revealed that melatonin can effectively alleviate spermatogenic disorders in dairy goats caused by HS. This beneficial effect was primarily achieved through the modulation of gut microbiota, which subsequently inhibited the excessive synthesis of AA in testicular tissue. These discoveries are of great significance for preventing or improving the decline in male livestock reproductive performance caused by HS, enhancing the reproductive efficiency of elite male breeds, and ultimately improving the production efficiency of animal husbandry. Video Abstract

Mpox is a zoonotic disease caused by the monkeypox virus (MPXV). Diagnosing and treating the disease has become a global health concern requiring close attention to its spread to non-endemic regions. Clinical diagnosis is based on laboratory test results. Conventional detection techniques include real-time quantitative polymerase chain reaction (qPCR), genome sequencing, antigen and antibody identification, and virus isolation. Nevertheless, these methods fall short of rapidly and efficiently identifying MPXV, as they require specialized training, specific laboratory environments, and professional-grade equipment. Emerging technologies offer complementary advantages to meet diverse diagnostic needs, including various point-of-care testing (POCT) approaches and integrating biosensors with rapid detection techniques. This review discusses prospective future research avenues for MPXV detection, examining the advances and challenges of various detection techniques which may contribute to the ongoing elimination of mpox human-to-human transmission and serves as a reference for developing effective prevention and control strategies.

An efficient, speedy, multi-grooved (ESMG) mold was designed and manufactured for optimization to address issues such as low heat transfer rate, slow casting speed, and quality defects in traditional continuous casting molds. The flow resistance mechanism of multi-grooved channels with varying parameters was investigated by considering the ESMG geometric model, the convective heat transfer characteristic variation trends were revealed with different channel designs. Considering constraints of the dimensional chain and supply pressure, variation trends and mechanisms of the pressure drop, flow rate loss, and convective heat transfer coefficient of the ESMG mold were explored using multiple channel variables. Based on the numerical model of the ESMG channel, temperature variation trends in the copper mold were verified by comparison with relevant literature data, supporting the convective-heat-transfer model and variation trends of the ESMG mold. A high-efficiency heat-transfer ESMG assembly that casts U71Mn high-carbon large rectangular billets was fabricated, achieving a closed-loop dimensional chain and replacing traditional molds. Experimental validation on the continuous casting machine (CCM) proved directly that redesigning the ESMG mold cooling channel improved heat transfer efficiency and reduced CO2 emissions. After 504 h on the CCM, the ESMG mold casting speed increased from 1.1 to 1.6 m/min, the heat transfer efficiency was 17.6% higher than that of traditional molds and CO2 emissions were estimated to decrease by 31.2%. The billets produced by the ESMG mold had no quality defects in shape or surface with the original casting conditions, which provided enhanced support for accelerating continuous casting lines.

Abstract Background Data on the effectiveness of erector spinae plane block (ESPB) for patients undergoing liver surgeries is limited and inconclusive. We hereby aimed to systematically review if ESPB can provide adequate analgesia after liver surgery. Methods PubMed, CENTRAL, Scopus, Embase, and gray literature were examined up to 25th April 2023 for randomized controlled trials (RCTs) comparing ESPB with control or spinal analgesia. Results Nine RCTs were included of which three compared ESPB with spinal analgesia. 24-hour opioid consumption did not differ significantly between ESPB vs. control (MD: -35.25 95% CI: -77.01, 6.52 I2 = 99%) or ESPB vs. spinal analgesia (MD: 2.32 95% CI: -6.12, 10.77 I2 = 91%). Comparing pain scores between ESPB and control, a small but significant effect favoring ESPB was noted at 12 h and 48 h, but not at 6–8 h and 24 h. Pain scores did not differ between ESPB and spinal analgesia. The risk of postoperative nausea and vomiting was also not significantly different between ESPB vs. control or spinal analgesia. GRADE assessment shows moderate certainty of evidence. Conclusion ESPB may not provide any significant postoperative analgesia in liver surgery patients. There was a tendency of reduced opioid consumption with ESPB. Limited data also showed that ESPB and spinal analgesia had no difference in pain scores and 24-hour analgesic consumption.

Thyroid-stimulating hormone (TSH) is a pituitary hormone that stimulates the thyroid gland to produce and release thyroid hormones, primarily thyroxine and triiodothyronine. These hormones are key players in body–brain communication, influencing various physiological processes, including the regulation of metabolism (both peripheral and central effects), feedback mechanisms, and lipid metabolism. Recently, the increasing incidence of abnormal lipid metabolism has highlighted the link between thyroid function and lipid metabolism. Evidence suggests that TSH can affect all bodily systems through body–brain communication, playing a crucial role in growth, development, and the regulation of various physiological systems. Lipids serve dual purposes: they are involved in energy storage and metabolism, and they act as vital signaling molecules in numerous cellular activities, maintaining overall human health or contributing to various diseases. This article reviews the role of TSH in regulating lipid metabolism via body–brain crosstalk, focusing on its implications for common lipid metabolism disorders such as obesity, atherosclerosis, nonalcoholic fatty liver disease, neuropsychiatric disorders (including Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and depression), and cerebrovascular disorders such as stroke.

Objective: To evaluate the performance of maternal factors, biophysical and biochemical markers at 11–13 + 6 weeks’ gestation in the prediction of gestational diabetes mellitus with or without large for gestational age (GDM ± LGA) fetus and great obstetrical syndromes (GOS) among singleton pregnancy following in-vitro fertilisation (IVF)/embryo transfer (ET). Materials and methods: A prospective cohort study was conducted between December 2017 and January 2020 including patients who underwent IVF/ET. Maternal mean arterial pressure (MAP), ultrasound markers including placental volume, vascularisation index (VI), flow index (FI) and vascularisation flow index (VFI), mean uterine artery pulsatility index (mUtPI) and biochemical markers including placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 11–13 + 6 weeks’ gestation. Logistic regression analysis was performed to determine the significant predictors of complications. Results: Among 123 included pregnancies, 38 (30.9%) had GDM ± LGA fetus and 28 (22.8%) had GOS. The median maternal height and body mass index were significantly higher in women with GDM ± LGA fetus. Multivariate logistic regression analysis demonstrated that in the prediction of GDM ± LGA fetus and GOS, there were significant independent contributions from FI MoM (area under curve (AUROC) of 0.610, 95% CI 0.492–0.727; p = 0.062) and MAP MoM (AUROC of 0.645, 95% CI 0.510–0.779; p = 0.026), respectively. Conclusion: FI and MAP are independent predictors for GDM ± LGA fetus and GOS, respectively. However, they have low predictive value. There is a need to identify more specific novel biomarkers in differentiating IVF/ET pregnancies that are at a higher risk of developing complications.

Background ICU patients have a high incidence of VTE. The American College of Chest Physicians antithrombotic practice guidelines recommend assessing the risk of VTE in all ICU patients. Although several VTE risk assessment tools exist to evaluate the risk factors among hospitalized patients, there is no validated tool specifically for assessing the risk of VTE in ICU patients. Methods A retrospective corhort study was conducted between June 2018 and October 2022. We obtained data from the electronic medical records of patients with a variety of diagnoses admitted to a mixed ICU. Multivariable logistic regression analysis was used to evaluate the independent risk factors of VTE. Receiver operating characteristic (ROC) curves were used to analyse the predictive accuracy of different tools. Results A total of 566 patients were included, and VTE occurred in 89 patients (15.7%), 62.9% was asymptomatic VTE. A prediction model (the ICU-VTE prediction model) was derived from the independent risk factors identified using multivariate analysis. The ICU-VTE prediction model included eight independent risk factors: history of VTE (3 points), immobilization ≥4 days (3 points), multiple trauma (3 points), age ≥70 years (2 points), platelet count >250 × 10 3 /μL (2 points), central venous catheterization (1 point), invasive mechanical ventilation (1 point), and respiratory failure or heart failure (1 point). Patients with a score of 0–4 points had a low (1.81%) risk of VTE. Patients were at intermediate risk, scoring 5–6 points, and the overall incidence of VTE in the intermediate-risk category was 17.1% (odds ratio [OR], 11.1; 95% confidence interval [CI], 4.2-29.4). Those with a score ≥7 points had a high (44.1%) risk of VTE (OR, 42.6; 95% CI, 16.4-110.3). The area under the curve (AUC) of the ICU-VTE prediction model was 0.838, and the differences in the AUCs were statistically significant between the ICU-VTE prediction model and the other three tools (ICU-VTE score, Z = 3.723, P

Abstract To assess the ameliorative effect of ursodeoxycholic acid (UDCA) on hydrogen peroxide (H2O2)-induced hepatocyte injury. In our in vivo experiments, we modelled hyperlipidemia in ApoE−/− mice subjected to a 3-month high-fat diet and found that HE staining of the liver showed severe liver injury and excessive H2O2 was detected in the serum. We modelled oxidative stress injury in L02 cells by H2O2 in vitro and analyzed the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and related genes. UDCA significantly improved the level of oxidative stress in H2O2-injured L02 cells (P

Abstract Sequencing strategies have continually advanced, with high-throughput sequencing (HTS) technologies emerging as pivotal tools in plant phylogenomics. As a standard form of target capture sequencing, hybridization target enrichment sequencing (Hyb-seq) is innovative and flexible, and then HTS strategy is widely adopted in phylogenomics. The universal Angiosperms353 probe sets (Angiosperms353) are instrumental in Hyb-seq and have been witnessed increased application in recent years. This review integrates numerous publications and empirical datasets to comprehensively assess the potential applications of Angiosperms353. Through evaluations using 18-taxa and 343-taxa genomic datasets, this review explores potential factors influencing Angiosperms353 gene capture. The RNA-seq strategy yielded the highest number of Angiosperms353 genes, followed by whole-genome sequencing and genome skimming. Increased sequencing depth enhanced gene capture yields, and no evident bias was observed across all tested angiosperm groups. In the genomics era with extensive HTS data, this review provides comprehensive guidelines for the practical application of Angiosperms353, promoting resource recycling and maximizing genomic data sharing and utilization.

Abstract The goal of this study was to use a new interpretable machine-learning framework based on max-logistic competing risk factor models to identify a parsimonious set of differentially expressed genes (DEGs) that play a pivotal role in the development of colorectal cancer (CRC). Transcriptome data from nine public datasets were analyzed, and a new Chinese cohort was collected to validate the findings. The study discovered a set of four critical DEGs - CXCL8, PSMC2, APP, and SLC20A1 - that exhibit the highest accuracy in detecting CRC in diverse populations and ethnicities. Notably, PSMC2 and CXCL8 appear to play a central role in CRC, and CXCL8 alone could potentially serve as an early-stage marker for CRC. This work represents a pioneering effort in applying the max-logistic competing risk factor model to identify critical genes for human malignancies, and the interpretability and reproducibility of the results across diverse populations suggests that the four DEGs identified can provide a comprehensive description of the transcriptomic features of CRC. The practical implications of this research include the potential for personalized risk assessment and precision diagnosis and tailored treatment plans for patients.

Social media is an important driver of firm success by providing an avenue for stakeholder engagement. Operating in a highly complex and competitive environment, firms in the ship management industry can utilise social media platforms to engage with their stakeholders, which can enhance stakeholder satisfaction and loyalty. However, stakeholder engagement rates can vary, with some posts generating more engagement than others. Drawing on the perceived value and word-of-mouth psychological motivation theories, this study introduces a theoretical model to identify and examine factors influencing stakeholder engagement on LinkedIn in the ship management industry. A hierarchical regression analysis is conducted on the posts of ten ship management firms to study the influence of content type and message characteristics variables on engagement rates. The results revealed nine variables that can significantly influence stakeholder engagement. They are links, corporate brand names, call-to-actions, message length, tangible resources, social content, emotional content, first-person texts, and emojis. The findings provide recommendations for firms in the ship management industry in terms of the message strategies to incorporate into their posts to encourage higher engagement rates. This study also enriches literature for stakeholder engagement on social media.

Fe-OC is crucial for SOC preservation in the global ecosystem. However, there is still significant uncertainty in the determination methods of Fe-OC, and these methods are often not calibrated to each other, making the Fe-OC content by different methods impossible to compare. Here, Fe-OC is analyzed by the CBD method and the SD method from 45 soils from different land types (e.g., wetland, grassland, and forest) to compare and analyze the uncertainty and influencing factors between the two methods. Our results showed that the Fe-OC contributions to SOC (fFe-OC) measured by CBD and SD methods were significantly lower in the wetland ecosystem than in grassland and forest ecosystems. The Fe-OC content and fFe-OC in the grassland ecosystem was significantly higher using the CBD method compared to the SD method, with no significant difference between the methods in wetland and forest ecosystems. The random forest model revealed that Fe-OCCBD content was mainly affected by C/N, Clay%, and TC, whereas SOC, total nitrogen, and soil inorganic carbon were the main influences on Fe-OCSD. Taken together, our findings highlight the importance of incorporating ecosystem types and soil properties into soil carbon estimation models when predicting and estimating Fe-OC and its contribution to SOC.

Omni-channel retailing is a novel form that combines online, offline, and mobile channels to provide consumers with a seamless shopping experience. Nevertheless, the implementation of omni-channel retailing necessitates effective logistics support. Hence, the quality of logistics services is critical for omni-channel retailing services. This research aims to investigate logistics service quality (LSQ) and its impact on consumer satisfaction by combining the decomposed SERVQUAL framework, Kano model and hierarchical regression analysis. A total of 460 valid responses were obtained. Building upon the SERVQUAL framework, this study presents a comprehensive framework for evaluating omni-channel retail logistics service quality. Using the Kano model, 11 logistics service quality attributes were categorised into three categories: must-be, one-dimensional, and attractive, based on their respective impact on satisfaction. The results of the hierarchical regression analysis confirm that the attributes belonging to the must-be category exert the most significant influence on satisfaction. The findings add to theoretical studies of omni-channel retailing LSQ and provide insights for omni-channel retailers and logistics service providers.

Abstract Bacterial wound infections are a serious threat due to the emergence of antibiotic resistance. Herein, we report an innovative hybrid nanozyme independent of antibiotics for antimicrobial wound healing. The hybrid nanozymes are fabricated from ultra-small Au NPs via in-situ growth on metal-organic framework (MOF)-stabilised Fe3O4 NPs (Fe3O4@MOF@Au NPs, FMA NPs). The fabricated hybrid nanozymes displayed synergistic peroxidase (POD)-like activities. It showed a remarkable level of hydroxyl radicals (·OH) in the presence of a low dose of H2O2 (0.97 mM). Further, the hybrid FMA nanozymes exhibited excellent biocompatibility and favourable antibacterial effects against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The animal experiments indicated that the hybrid nanozymes promoted wound repair with adequate biosafety. Thus, the well-designed hybrid nanozymes represent a potential strategy for healing bacterial wound infections, without any toxic side effects, suggesting possible applications in antimicrobial therapy.

Phylogenetic relationships of Scrophulariaceae s. l.（sensu lato）and the closely related groups were explored with 129 plastid genomes representing 107 genera. Plastome sequences were downloaded from the GenBank. Based on coding sequences (CDS), phylogenetic trees were reconstructed using maximum likelihood（ML）and Bayesian inference（BI）approaches. The ML and BI analyses shared the same topology and the main clades were consistently recovered with high support. Of the 129 total nodes, 123 were supported by ML bootstrap value ≥70%. The result were as follows：（1）Scrophulariaceae s. l. was confirmed as polyphyletic. Fifty-one species with representatives of 37 genera from the Scrophulariaceae s.l. were assigned to seven families. These were Orobanchaceae, Paulowniaceae, Wightiaceae, Mazaceae, Linderniaceae, Scrophulariaceae s. s.（sensu stricto）, and Plantaginaceae.（2）Scrophulariaceae s.s. was a monophyletic group. In addition to the recognition of eight genera（including Bontia, Calamphoreus, Diocirea, Eremophila, Glycocystis, Leucophyllum, Scrophularia and Verbascum）comprised primarily of former members of Scrophulariaceae s.l., Buddleja which was originally placed in Loganiaceae, and Myoporum, traditionally placed in the Myoporaceae had been demonstrated to belong to this clade.（3）The Lamiales was monophyletic. Fourteen well-supported monophyletic clades were obtained corresponding to each family (Wightiaceae and Pedaliaceae for which only one species had been contained were not included). The relationships among the families were well resolved. Oleaceae formed a well-supported clade that was distinct from core Lamiales. Within the core Lamiales, four clades (Gesneriaceae, Plantaginaceae, Scrophulariaceae, and Linderniaceae) diverged before the remaining families grouping in two sister clades. Within one clade, two moderately to highly supported subclades were recovered. Lentibulariaceae was resolved as sister group to Acanthaceae, and Pedaliaceae was sister to Verbenaceae + Bignoniaceae. The other clade contained six families, with Lamiaceae, Mazaceae, Wightiaceae + Phrymaceae, and Paulowniaceae successively sister to Orobanchaceae. The results of our analyses indicate that the traditional Scrophulariaceae are an unnatural assemblage of plants distributed throughout the phylogenentic tree of Lamiales. Phylogenomics analyses based on plastid organelle have shown good potential for phylogenetic inference in Scrophulariaceae, more taxonomic sampling are needed to enhance our understanding of phylogenetic relationships of Scrophulariaceae in future studies.

As a critical component in industrial production, pipelines face the risk of failure due to long-term corrosion. In recent years, acoustic emission (AE) technology has demonstrated significant potential in online pipeline monitoring. However, the interference of flow-induced noise seriously hinders the application of acoustic emission technology in pipeline corrosion monitoring. Therefore, a pattern-recognition model for online pipeline AE monitoring signals based on blind source separation (BSS) and a convolutional neural network (CNN) is proposed. First, the singular spectrum analysis (SSA) was employed to transform the original AE signal into multiple observed signals. An independent component analysis (ICA) was then utilized to separate the source signals from the mixed signals. Subsequently, the Hilbert–Huang transform (HHT) was applied to each source signal to obtain a joint time–frequency domain map and to construct and compress it. Finally, the mapping relationship between the pipeline sources and AE signals was established based on the CNN for the precise identification of corrosion signals. The experimental data indicate that when the average amplitude of flow-induced noise signals is within three times that of corrosion signals, the separation of mixed signals is effective, and the overall recognition accuracy of the model exceeds 90%.

Beryllium is a lightweight metal that is toxic to humans. The critical health effects related to beryllium exposure are liver toxicity, immune system toxicity, and chronic beryllium disease (CBD). This study investigated the effects of occupational beryllium exposure on liver and lung function and hematologic parameters among beryllium smelter workers. A cross-sectional study was performed by comparing 65 exposed workers and 34 non-exposed workers. Health information was collected through questionnaire surveys and biochemical tests. The concentration of urinary beryllium was determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The findings indicated that the urinary beryllium levels of the exposed workers and the controls were 0.48 (0.115, 1.19) μg/mL and 0.0125 (0.005, 0.005) μg/mL, respectively (p < 0.001). Compared with the controls, the exposed workers showed a significant increase in serum alanine aminotransferase (ALT) level, hemoglobin (HGB) concentration, white blood cell (WBC) count, red blood cell (RBC) count, and systolic and diastolic blood pressure (SBP, DBP) (p < 0.05). Furthermore, the HGB concentration and ALT level were significantly correlated with the concentration of beryllium in urine (p < 0.05). The exposed workers had increased urinary concentrations of beryllium, in contrast to the control subjects. Moreover, the urinary beryllium levels among the exposed workers are much higher than that in the Chinese general population. Beryllium-exposed workers may be at risk of liver and hematologic impairments.

Abstract The development of atherosclerosis (AS) is closely linked to changes in the plaque microenvironment, which consists primarily of the cells that form plaque and the associated factors they secrete. The onset of inflammation, lipid deposition, and various pathological changes in cellular metabolism that accompany the plaque microenvironment will promote the development of AS. Numerous studies have shown that oxidative stress is an important condition that promotes AS. The accumulation of reactive oxygen species (ROS) is oxidative stress’s most important pathological change. In turn, the effects of ROS on the plaque microenvironment are complex and varied, and these effects are ultimately reflected in the promotion or inhibition of AS. This article reviews the effects of ROS on the microenvironment of atherosclerotic plaques and their impact on disease progression over the past five years and focuses on the progress of treatment strategies based on scavenging ROS of nanoparticles for AS. Finally, we also discuss the prospects and challenges of AS treatment.

Extracellular vesicles (EVs) play a crucial role in intercellular communication. Characterizing EV protein composition is essential to understand EV function(s). Isolating EVs from cell culture medium is a common approach to study EVs, but it remains unclear whether EVs isolated from in vitro conditions accurately reflect physiological conditions of the same source in vivo tissues. Here, we analyzed the protein composition of EVs isolated from freshly dissected mouse forebrain and primary dissociated mouse forebrain culture medium. In total, 3,204 and 3,583 proteins were identified in EVs isolated in vivo and in vitro, respectively. Among the proteins identified from both EV sources, there was substantial overlap (~86%). While the overall proteome compositions were very similar, in vitro EVs were relatively enriched with transmembrane/GPI-anchored membrane and cytosolic proteins (MISEV2023 category 1 and 2) typically associated with EVs. Conversely, while both in vivo and in vitro EVs express likely non-EV proteins (MISEV2023 category 3), the in vivo samples were significantly more enriched with these probable contaminants, specifically ribosomal proteins. Our findings highlight that in vitro EVs may be representative of in vivo EVs when isolated from the same source tissue using similar methodology; however, each population of EVs have differences in both total and, primarily, relative protein expression likely due to differing levels of co-eluting contaminants. Therefore, these points must be considered when interpreting results of EV studies further suggesting that improved methods of isolation to reduce non-EV contaminants should be further investigated.

The rural B&B industry is a key component of rural tourism, local economic development, and the wider rural revitalization strategy. Despite the abundance of tourism resources in Yunnan, the B&B sector faces significant challenges. It is therefore imperative to accurately identify the most pressing issues within the current B&B industry and formulate appropriate solutions to advance Yunnan's rural revitalization efforts. This study uses recent reviews of rural B&Bs on Ctrip.com and employs machine learning techniques, including Bert, CNN, LSTM, and GRU, to identify the key management challenges currently facing Yunnan's rural B&B industry. An analysis is then conducted to identify the key stakeholders involved in the process of improving the management of Yunnan's B&Bs. To assess the willingness of each stakeholder to support the improvement of the rural B&B industry, this paper establishes a three-party evolutionary game model and examines the dynamic evolutionary process of management improvement within Yunnan's rural B&B industry. Two scenarios of evolutionarily stable strategies are analyzed, and parameters impacting stakeholders' strategy choices are simulated and evaluated. The results show that: i) Improving the "human factor" is the top priority for the current management improvement because tourists are most concerned about the emotional experience. Operators need to focus on improving service attitude and emotional experience; ii) The main stakeholders in the current management optimization process of Yunnan B&Bs are the local government, B&B operators, and tourists. Under appropriate conditions, the evolutionarily stable strategy of (1, 1, 1) is reachable. iii) variables such as additional costs, tourists' choice preferences, and government penalties significantly affect the strategy choices of stakeholders, especially B&B operators. This paper offers effective strategies for improving B&B management that can benefit the government, B&B operators, and tourists, and ultimately contribute to the promotion of quality rural revitalization. The paper not only identifies focal areas for improving B&B management in rural Yunnan, but also provides an in-depth understanding of stakeholder dynamics. As a result, it provides valuable insights to further the cause of quality rural revitalization.

Objective. Intensive care unit (ICU)-acquired weakness often occurs in patients with invasive mechanical ventilation (IMV). Early active mobility may reduce ICU-acquired weakness, improve functional status, and reduce disability. The aim of this study was to investigate whether high-intensity early mobility improves post-ICU discharge functional status of IMV patients. Methods. 132 adult patients in the ICU who were undergoing IMV were randomly assigned into two groups with a ratio of 1 : 1, with one group received high-intensity early mobility (intervention group, IG), while the other group received conventional treatment (control group, CG). The functional status (Barthel Index (BI)), capacity of mobility (Perme score and ICU Mobility Scale (IMS)), muscle strength (Medical Research Council sum scores (MRC-SS)), mortality, complication, length of ICU stay, and duration of IMV were evaluated at ICU discharge or after 3-month of ICU discharge. Results. The patient’s functional status was improved (BI scores 90.6 ± 18.0 in IG vs. 77.7 ± 27.9 in CG; p=0.005), and capacity of mobility was increased (Perme score 17.6 ± 7.1 in IG vs. 12.2 ± 8.5 in CG, p

Abstract Background To compare the oncological outcomes of patients with FIGO 2018 stage IIIC cervical cancer (CC) involving different local tumor factors who underwent abdominal radical hysterectomy (ARH), neoadjuvant chemotherapy and radical surgery (NACT), or radical chemoradiotherapy (R-CT). Methods Based on tumor staging, patients with stage IIIC were divided into T1, T2a, T2b, and T3 groups. Kaplan–Meier and Cox proportional hazards regression analysis were used to compare their overall survival (OS) and disease-free survival (DFS) of 5 years. Results We included 4,086 patients (1,117, 1,019, 869, and 1,081 in the T1, T2a, T2b, and T3 groups, respectively). In the T1 group, NACT was correlated with a decrease in OS (hazard ratio [HR] = 1.631, 95% confidence interval [CI]: 1.150–2.315, P = 0.006) and DFS (HR = 1.665, 95% CI: 1.255–2.182, P

Abstract Aims We aimed to explore the heterogeneous treatment effects (HTEs) for spironolactone treatment in patients with Heart failure with preserved ejection fraction (HFpEF) and examine the efficacy and safety of spironolactone medication, ensuring a better individualized therapy. Methods and results We used the causal forest algorithm to discover the heterogeneous treatment effects (HTEs) from patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Cox regressions were performed to assess the hazard ratios (HRs) of spironolactone medication for cardiovascular death and drug discontinuation in each group. The causal forest model revealed three representative covariates and participants were partitioned into four subgroups which were Group 1 (baseline BMI ≤ 31.71 kg/m2 and baseline ALP ≤ 80 U/L, n = 759); Group 2 (BMI ≤ 31.71 kg/m2 and ALP > 80 U/L, n = 1088); Group 3 (BMI > 31.71 kg/m2, and WBC ≤ 6.6 cells/μL, n = 633); Group 4 (BMI > 31.71 kg/m2 and WBC > 6.6 cells/μL, n = 832), respectively. In the four subgroups, spironolactone therapy reduced the risk of cardiovascular death in high‐risk group (Group 4) with both high BMI and WBC count (HR: 0.76; 95% CI 0.58 to 0.99; P = 0.045) but increased the risk in low‐risk group (Group 1) with both low BMI and ALP (HR: 1.45; 95% CI 1.02 to 2.07; P = 0.041; P for interaction = 0.020) but showed similar risk of drug discontinuation (P for interaction = 0.498). Conclusion Our study manifested the HTEs of spironolactone in patients with HFpEF. Spironolactone treatment in HFpEF patients is feasible and effective in patients with high BMI and WBC while harmful in patients with low BMI and ALP. Machine learning model could be meaningful for improved categorization of patients with HFpEF, ensuring a better individualized therapy in the clinical setting.

Abstract Background According to epidemiological studies, gingivitis is a common disease. However, its morbidity, considerably varies among individual. This study aimed to investigate the epidemiological characteristics of gingivitis, including prevalence, severity, intraoral distribution, and associated risk factors, in children aged 6–12 years in Jinzhou, China. Methods A multistage, whole-group, randomized sample of 2880 children aged 6–12 years in Jinzhou City, China, was selected and clinically examined. Each selected child completed a questionnaire on sociodemographic factors and oral health behaviors in cooperation with the investigator and teacher. Gingival bleeding refers to the bleeding of 10% or more teeth under the condition of ingivitis. Gingivitis was further categorized into localized gingivitis (30% ≥ number of teeth positive for gingival bleeding ≥ 10%) and generalized gingivitis (number of positive for gingival bleeding > 30%). The score of gingival bleeding was recorded using the Gingival Index. Results The prevalence of gingivitis in children aged 6–12 years in Jinzhou was 28.58%, including 701 cases of localized gingivitis (24.3%) and 122 cases of generalized gingivitis (4.2%). There were 429 cases (28.3%) of gingivitis in males and 394 cases (28.9%) in females, with no statistically significant difference in prevalence between males and females (P > 0.05). Chi-square tests and binary logistic regression analysis showed that aging, dental calculus, plaque, and dental crowding were significantly associated with a high prevalence of gingivitis. Conclusions Our study showed that dental calculus, large amount dental plaque, poor oral health behavior, and oral health awareness are associated with the prevalence of gingivitis and maintaining children's oral health requires professional guidance and regular preventive care.

Fly ash was modified using calcium oxide and carbon dioxide. The morphology of precipitated calcium carbonate was controlled by adding different crystal-shape-forming additives. Effects of sodium hexametaphosphate, zinc chloride, sodium tetraborate decahydrate, and aluminium chloride on the crystal shape of precipitated calcium carbonate were studied. The effects of crystal-shaped additives of precipitated calcium on the whiteness of modified fly ash and hand sheets were analyzed. The results showed that the addition of ZnCl2 (0.35%) can play a role in coating fly ash well. The coating effect of the acicular, chain, and lamellar precipitated calcium carbonate on the surface of fly ash was slightly less effective than that of globular crystals.

Birth weight is an indicator linking intrauterine environmental exposures to later-life diseases, and intrauterine metal exposure may affect birth weight in a sex-specific manner. We investigated sex-specific associations between prenatal exposure to metal mixtures and birth weight in a Chinese birth cohort. The birth weight of 1296 boys and 1098 girls were recorded, and 10 metals in maternal urine samples collected during pregnancy were measured using inductively coupled plasma mass spectrometry. Bayesian Kernel Machine Regression was used to estimate the association of individual metals or metal mixtures and birth weight for gestational age (BW for GA). The model showed a sex-specific relationship between prenatal exposure to metal mixtures and BW for GA with a significant negative association in girls and a non-significant positive association in boys. Cadmium (Cd) and nickel (Ni) were positively and negatively associated with BW for GA in girls, respectively. Moreover, increasing thallium (Tl) concentration lowered the positive association between Cd and BW for GA and enhanced the negative association between Ni and BW for GA in girls. When exposure to other metals increased, the positive association with Cd diminished, whereas the negative association with Ni or Tl increased. Our findings provide evidence supporting the complex effects of intrauterine exposure to metal mixtures on the birth weight of girls and further highlight the sex heterogeneity in fetal development influenced by intrauterine environmental factors.

IntroductionWe previously discovered a pyridazine derivative compound series that can improve cognitive functions in mouse models of Alzheimer’s disease. One of the advanced compounds from this series, LDN/OSU-0215111-M3, was selected as the preclinical development candidate. This compound activates local protein translation at the perisynaptic astrocytic process (PAP) and enhances synaptic plasticity sequentially. While biochemical evidence supports the hypothesis that the compound enhances the structural plasticity of the tripartite synapse, its direct structural impact has not been investigated.MethodsVolume electron microscopy was used to study the hippocampal tripartite synapse three-dimensional structure in 3-month-old wild-type FVB/NJ mice after LDN/OSU-0215111-M3 treatment.ResultsLDN/OSU-0215111-M3 increased the size of tertiary apical dendrites, the volume of mushroom spines, the proportion of mushroom spines containing spine apparatus, and alterations in the spine distribution across the surface area of tertiary dendrites. Compound also increased the number of the PAP interacting with the mushroom spines as well as the size of the PAP in contact with the spines. Furthermore, proteomic analysis of the isolated synaptic terminals indicated an increase in dendritic and synaptic proteins as well as suggested a possible involvement of the phospholipase D signaling pathway. To further validate that LDN/OSU-0215111-M3 altered synaptic function, electrophysiological studies showed increased long-term potentiation following compound treatment.DiscussionThis study provides direct evidence that pyridazine derivatives enhance the structural and functional plasticity of the tripartite synapse.

The basic helix-loop-helix (bHLH) transcription factor family is the second-largest family in plants, where it plays essential roles in development, and the responses to multiple abiotic and biotic stressors. However, little information is available about this gene family in Prunus mume, which is widely cultivated in East Asia as an ornamental fruit tree. Here, 100 PmbHLH genes were identified, and their evolution and functions were explored in P. mume for the first time. The PmbHLH genes were classified into 21 subfamilies. The chromosomal distribution, physicochemical properties, bHLH domain, conserved motif, and intron/exon compositions were also analyzed. Furthermore, the evolutionary pattern, divergence time of the PmbHLH family, and genetic relationships among P. mume, Arabidopsis thaliana, and Prunus persica and Fragaria vesca of Rosaceae were explored. The functional prediction analysis of these PmbHLHs indicated that their functions varied, and included participating in the formation of organs and tissues, responding to stress, and the biosynthesis and metabolism of hormones and other secondary metabolites. Interestingly, expression analyses of PmbHLHs also revealed diverse expression patterns. Most of the PmbHLH genes were highly expressed in roots and stems, and a few were highly expressed in leaves, buds, and fruits, indicating tissue expression specificity. Eight PmbHLH genes, which were upregulated during low-temperature stress, may have critical roles in the response to cold stress. Ten PmbHLHs were differentially expressed between weeping and upright branches in a P. mume F1 population. These results shed light on the structure and evolution of the PmbHLH gene family, and lay a foundation for further functional studies of the bHLH genes.

Monkfish (Lophius litulon) is a nutritious marine product that has attracted increasing attention. In this study, we demonstrated that the monkfish protein hydrolysate (MPH) administration could significantly prolonged the exhaustive swimming time of mice, and increased the hepatic glycogen (HG) level, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxides (GSH-PX) activities; in addition, markedly decreased the blood urea nitrogen (BUN), blood lactic acid (BLA), malonaldehyde (MDA) levels and lactate dehydrogenase (LDH) activity. Furthermore, the MPH administration also enhanced the proliferation of spleen lymphocytes and the activity of natural killer (NK) cells in mice. Besides, 43 peptides from MPH that rich in Phe, His, Ile, Leu and Thr were identified. Finally, 1245 of differentially expressed genes (DEGs) in NC vs MPH-H groups were obtained by transcriptome analysis, and GO classification and enrichment of KEGG pathway were studied. In conclusion, MPH treatment had the anti-fatigue and immunological effects in mice.

The rapid development of modern logistics and e-commerce highlights the importance of exploring various modes of transportation in the last-mile delivery (LMD) process. However, no comprehensive studies exist in the literature exploring all modes of LMD transportation, the changes in these transportation modes, and the commonalities between them. In this study, we address this gap by conducting a systematic review of 150 academic journal articles utilizing a combination of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) content analysis and text mining analysis. Nine primary transportation methods (parcel lockers, autonomous drones, trucks, bicycles, crowd logistics, electric vehicles, tricycles, autonomous robots, and autonomous vehicles) are identified in this research. Additionally, we provide an analysis of the historical changes in these transportation modes in LMD. Using a bottom-up induction method, we identify the three major clusters of scholarly focus in the LMD literature: emphasis on value co-creation between consumers and logistics providers, practical delivery performance (path optimization or algorithms), and environmental friendliness. Further, we analyze the main themes under each cluster, leading to the identification of opportunities, challenges, and future research agendas. Our findings have implications for scholars, policymakers, and other stakeholders involved in LMD transportation modes.

Summary: Antibody-secreting B cells have long been considered the central element of gut homeostasis; however, tumor-associated B cells in human colorectal cancer (CRC) have not been well characterized. Here, we show that the clonotype, phenotype, and immunoglobulin subclasses of tumor-infiltrating B cells have changed compared to adjacent normal tissue B cells. Remarkably, the tumor-associated B cell immunoglobulin signature alteration can also be detected in the plasma of patients with CRC, suggesting that a distinct B cell response was also evoked in CRC. We compared the altered plasma immunoglobulin signature with the existing method of CRC diagnosis. Our diagnostic model exhibits improved sensitivity compared to the traditional biomarkers, CEA and CA19-9. These findings disclose the altered B cell immunoglobulin signature in human CRC and highlight the potential of using the plasma immunoglobulin signature as a non-invasive method for the assessment of CRC.

Currently, the recovery of cognitive function has become an essential part of stroke rehabilitation. DL-3-n-butylphthalide (NBP) is a neuroprotective reagent and has been used in stroke treatment. Clinical studies have confirmed that NBP can achieve better cognitive outcomes in ischemic stroke patients than in healthy controls. In this study, we aimed to investigate the influences of NBP on cognitive function in an ischemic reperfusion (I/R) rat model. Our results showed that NBP profoundly decreased neurological scores, reduced cerebral infarct areas and enhanced cerebral blood flow (CBF). NBP potently alleviated poststroke cognitive impairment (PSCI) including depression-like behavior and learning, memory and social cognition impairments, in I/R rats. NBP distinctly suppressed the activation of microglia and astrocytes and improved neuron viability in the ischemic brain. NBP inhibited the expression of inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), by targeting the nuclear factor kappa B/inducible nitric oxide synthase (NF-κB/iNOS) pathway and decreased cerebral oxidative stress factors, including reactive oxygen species (ROS) and malondialdehyde (MDA), by targeting the kelch like ECH associated protein 1/nuclear factor-erythroid 2 p45-related factor 2 (Keap1/Nrf2) pathway in the ischemic brain. The current study revealed that NBP treatment improved neurological function and ameliorated cognitive impairment in I/R rats, possibly by synergistically suppressing inflammation and oxidative stress.

Abstract Background Multidrug resistance (MDR) is the main challenge of successful chemotherapy for ovarian cancer patients, with 50% to 75% of ovarian cancer patients eventually relapsed due to it. One of the effective strategies for treating MDR and improving therapeutic efficiency of ovarian cancer is to use nanotechnology-based targeted drug delivery systems. In this study, a novel nano targeted co-delivery system modified by hyaluronic acid (HA) was developed by using gold nanorods coated with functionalized mesoporous silica nanoparticles (HA-PTX/let-7a-GNR@MSN) for combined delivery of hydrophobic chemotherapy drug Paclitaxel (PTX) and lethal-7a (let-7a), a microRNA (miR), to overcome MDR in ovarian cancer. Furthermore, we also analyzed the molecular mechanism of this nanotherapeutic system in the treatment of ovarian cancer. Results HA-modified nanocomplexes can specifically bind to the CD44 receptor, which is highly expressed in SKOV3/SKOV3TR cells, achieving effective cell uptake and 150% enhancement of tumor site permeability. The nanosystem realized the stable combination and protective transportation of PTX and miRs. Analysis of drug-resistant SKOV3TR cells and an SKOV3TR xenograft model in BALB/c-nude mice showed significant downregulation of P-glycoprotein in heterogeneous tumor sites, PTX release, and subsequent induction of apoptosis. More importantly, this nanosystem could synergistically inhibit the growth of ovarian tumors. Further studies suggest that mTOR-mediated signaling pathways play an important role in reversing drug resistance and inducing apoptosis. Conclusions To sum up, these data provide a model for overcoming PTX resistance in ovarian cancer. Graphical Abstract

Abstract Background Currently, there is no effective treatment for premature ovarian failure (POF), and stem cell therapy is considered the most promising treatment. Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) have shown good regenerative ability in various diseases, including POF; however, their underlying mechanism and dosage for POF treatment remain unclear. This study aimed to compare the effect of single and multiple injections of hUC-MSCs on ovarian function repair in chemotherapy-induced POF. Methods Female mice were intraperitoneally injected with 30 mg/kg busulfan and 120 mg/kg cyclophosphamide (CTX) to induce POF. In the single hUC-MSC injection group, hUC-MSCs were transplanted into mice D7 after CTX and busulfan administration, while in the multiple injection group, hUC-MSCs were transplanted on D7, D14, and D21 after CTX and busulfan administration. We evaluated the ovarian morphology, fertility, follicle-stimulating hormone and estradiol concentrations, follicle count, POF model, and cell transplantation results. In addition, real-time polymerase chain reaction, immunohistochemistry, and miRNA and mRNA chips were used to evaluate the effect of the cell therapy. Results Ovary size, number of follicle at all developmental stages, and fertility were significantly reduced in the POF group compared with the control. Under hUC-MSC treatment, the ovarian morphology and follicle count were significantly restored, and fertility was significantly increased. By comparing the single and multiple hUC-MSC injection groups, we found that the anti-Müllerian hormone and Ki-67 levels were significantly increased in the multiple hUC-MSC group on D60 after chemotherapy. The expression of stimulating hormone receptors, inhibin α, and inhibin β was significantly restored, and the therapeutic effect was superior to that of the single hUC-MSC injection group. Conclusion These results indicate that hUC-MSCs can restore the structure of injured ovarian tissue and its function in chemotherapy-induced POF mice and ameliorate fertility. Multiple hUC-MSC transplantations have a better effect on the recovery of ovarian function than single hUC-MSC transplantation in POF.

Background: Pulmonary manifestations of systemic lupus erythematosus (SLE) are appearing in 4-5% of patients involving lung in almost half of the cases during the disease course. Objective: We compared the autoimmune pulmonary inflammation in the lung tissue of mice to determine the association between decreased expression levels of Forkhead Box J1 (FOXJ1) and the activation of the NF-κB pathway in autoimmune pulmonary inflammation of MRL/Lpr mice. Methods: The female BALB/c mice (n=6) and MRL/Lpr mice (n=30) were divided into 5 groups including a control group (BALB/c), and five MRL/Lpr mice groups (8W, 12W, 16W, 24W, and 32W). The infiltration of the inflammatory cells was determined in lung tissue by performing the histological analysis. The western blotting was used to examine the expression levels of the age-related FOXJ1, and p50 and p65 proteins in the lungs of MRL/Lpr mice. The expression levels of MMP2 and MMP9 were determined via immunohistochemistry and immunofluorescence. Results: There were severe infiltrates of lung cells with high levels of tracheal damage, perivascular injury and interstitial inflammatory cell infiltration when the MRL/Lpr mice from 16w to 32w comparing to the 8w old healthy MRL/Lpr mice in the control group (p

The unprecedented outbreak of the novel coronavirus has led to a great shift toward online retailing and accelerated the need for contactless delivery. This study investigates how technological and health belief factors influence consumer acceptance of autonomous delivery robots (ADRs). Anchored in four behavioral theories [i.e., technology acceptance model, health belief model, perceived value (VAL) theory and trust theory], a synthesized model is developed. A total of 500 valid responses were collected through an online questionnaire in Singapore, and structural equation modeling was conducted to examine the responses. The results revealed that perceived ease of use (EOU), perceived usefulness (UFN), perceived susceptibility (SUS), perceived severity (SEV), self-efficacy (SEL) and cues to action (CUE) have a positive and significant influence on consumers’ perceptions of the value of ADRs. The total effect analysis also showed that perceived VAL strongly affects consumer acceptance of ADRs. Academically, this study introduces both technological and health belief factors to explain consumer acceptance of ADRs. It also provides recommendations for policymakers and autonomous delivery robot developers on policy formulation, public communication, product design and infrastructure development.

Travel restrictions have harmed the cruise industry as a result of the COVID-19 pandemic. The goal of this study, which is attributed to permanent changes in the regulatory and social landscape, is to identify and examine the factors influencing post-COVID-19 cruise travel intention. To explain cruise travel intention, we developed a theoretical model incorporating health protection motivation, social learning and travel constraint theories. An online survey was conducted with 400 valid responses collected from Singapore. The theoretical model was estimated using structural equation modeling and the survey data. The findings indicate that (1) observing societal behavior, (2) observing the COVID-19 situation, (3) threat appraisal, and (4) coping appraisal all have a direct influence on travel constraint negotiation. Furthermore, travel constraint negotiation and societal observation have a direct impact on intention. An intriguing finding is that observing the COVID-19 situation has no effect on threat assessment, which can be attributed to pandemic fatigue. The findings allow for a set of recommendations to cruise companies and policymakers for post-COVID-19 cruise industry management.

BackgroundMicrosatellite instability (MSI) is associated with several tumor types and has become increasingly vital in guiding patient treatment decisions; however, reasonably distinguishing MSI from its counterpart is challenging in clinical practice.MethodsIn this study, interpretable pathological image analysis strategies are established to help medical experts to identify MSI. The strategies only require ubiquitous hematoxylin and eosin–stained whole-slide images and perform well in the three cohorts collected from The Cancer Genome Atlas. Equipped with machine learning and image processing technique, intelligent models are established to diagnose MSI based on pathological images, providing the rationale of the decision in both image level and pathological feature level.FindingsThe strategies achieve two levels of interpretability. First, the image-level interpretability is achieved by generating localization heat maps of important regions based on deep learning. Second, the feature-level interpretability is attained through feature importance and pathological feature interaction analysis. Interestingly, from both the image-level and feature-level interpretability, color and texture characteristics, as well as their interaction, are shown to be mostly contributed to the MSI prediction.InterpretationThe developed transparent machine learning pipeline is able to detect MSI efficiently and provide comprehensive clinical insights to pathologists. The comprehensible heat maps and features in the intelligent pipeline reflect extra- and intra-cellular acid–base balance shift in MSI tumor.

Abstract. Preeclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. This disorder has profound short-term and long-term impacts on both the affected woman's and her child's health. Early-onset PE requiring preterm delivery (preterm PE) is of particular importance because it is associated with a higher risk of adverse pregnancy outcomes than term PE. First trimester screening model developed by the Fetal Medicine Foundation (FMF), which uses Bayes-theorem to combine maternal characteristics and medical history together with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor, has been proven to be effective and have superior screening performance to that of traditional risk factor-based approach for the prediction of PE. Identification of high risk pregnant women for preterm PE and giving aspirin prophylaxis before 16th week of gestation would reduce the incidence of preterm PE. In Asia, although the prevalence of PE is slightly lower than the global estimation, early screening and prevention of this life-threatening condition is still crucial. The FMF Bayes-theorem based screening method has been validated in a large-scale prospective Asia-wide study and revealed that the first trimester triple test achieves the highest detection rate, compared with the traditional risk factor-based approaches, and that the screening performance is comparable to the published data from the FMF in East Asian women. However, in order to achieve optimal screening performance, the key is to establish standardized methods for biomarker measurements and regular biomarker quality assessment, as each biomarker is susceptible to inaccurate measurement, thus affecting performance of screening. Furthermore, it is of great importance to emphasize that the optimal preventive effect of aspirin on preterm PE is clearly associated with good compliance to treatment. In conclusion, global implementation of an effective first trimester “screen and prevent” program for preterm PE would provide the opportunity to reduce the risk of both short-term maternal and perinatal morbidity and mortality, with the possibility of intergenerational prevention of future chronic diseases for both the mother and her offspring.

Abstract Background The number of cumulative confirmed cases of COVID-19 in the United States has risen sharply since March 2020. A county health ranking and roadmaps program has been established to identify factors associated with disparity in mobility and mortality of COVID-19 in all counties in the United States. The risk factors associated with county-level mortality of COVID-19 with various levels of prevalence are not well understood. Methods Using the data obtained from the County Health Rankings and Roadmaps program, this study applied a negative binomial design to the county-level mortality counts of COVID-19 as of August 27, 2020 in the United States. In this design, the infected counties were categorized into three levels of infections using clustering analysis based on time-varying cumulative confirmed cases from March 1 to August 27, 2020. COVID-19 patients were not analyzed individually but were aggregated at the county-level, where the county-level deaths of COVID-19 confirmed by the local health agencies. Clustering analysis and Kruskal–Wallis tests were used in our statistical analysis. Results A total of 3125 infected counties were assigned into three classes corresponding to low, median, and high prevalence levels of infection. Several risk factors were significantly associated with the mortality counts of COVID-19, where higher level of air pollution (0.153, P

The oligopeptide transporter (OPT) family is a group of proton-coupled symporters that play diverse roles, including metal homeostasis. However, little is known about this family of peanuts. To reveal the potential roles of AhOPT genes in Fe/Cd interactions, peanut AhOPT genes were genome-widely identified, and the relationships between gene expression and Cd accumulation were detected in two contrasting peanut cultivars (Fenghua 1 and Silihong) under Fe-sufficient or Fe-deficient conditions. A total of 40 AhOPT genes were identified in peanuts, which were divided into two subfamilies (PT and YS). Most AhOPT genes underwent gene duplication events predominated by whole-genome duplication. Clustered members generally have similar protein structures. However, gene structural divergences occurred in most of the duplicated genes. Transcription analysis revealed that AhOPT3.2/3.4 and AhYSL3.1/3.2 might be responsible for Fe deficiency tolerance, while AhOPT3.1/3.4, AhOPT7.1/7.2, and AhYSL1.1 be involved in Fe/Cd interactions. These genes might be regulated by transcription factors, including ATHB-12, ATHB-6, DIVARICATA, MYB30, NAC02, DOF3.4, IDD7, and LUX. Reduced expressions of AhYSL3.1/3.2 and higher expressions of AhOPT3.4 might contribute to higher Fe-deficiency tolerance in Silihong. Higher expression of AhOPT7.3 and AhOPT6.1 might be responsible for low Cd accumulation in Fenghua 1. Our results confirmed that AhOPT3/6/7 and AhYSL1/3 might be involved in the transport of Fe and/or Cd in peanuts and provided new clues to understanding potential mechanisms of Fe/Cd interactions.

Objective To develop and validate a generalized prediction model that can classify epidermal growth factor receptor (EGFR) mutation status in non–small cell lung cancer patients. Methods A total of 346 patients (296 in the training cohort and 50 in the validation cohort) from four centers were included in this retrospective study. First, 1085 features were extracted using IBEX from the computed tomography images. The features were screened using the intraclass correlation coefficient, hypothesis tests and least absolute shrinkage and selection operator. Logistic regression (LR), decision tree (DT), random forest (RF), and support vector machine (SVM) were used to build a radiomics model for classification. The models were evaluated using the following metrics: area under the curve (AUC), calibration curve (CAL), decision curve analysis (DCA), concordance index (C-index), and Brier score. Results Sixteen features were selected, and models were built using LR, DT, RF, and SVM. In the training cohort, the AUCs was .723, .842, .995, and .883; In the validation cohort, the AUCs were .658, 0567, .88, and .765. RF model with the best AUC, its CAL, C-index (training cohort=.998; validation cohort=.883), and Brier score (training cohort=.007; validation cohort=0.137) showed a satisfactory predictive accuracy; DCA indicated that the RF model has better clinical application value. Conclusion Machine learning models based on computed tomography images can be used to evaluate EGFR status in patients with non–small cell lung cancer, and the RF model outperformed LR, DT, and SVM.

Metal tolerance proteins (MTP) are Me2+/H+(K+) antiporters that play important roles in the transport of divalent cations in plants. However, their functions in peanut are unknown. In the present study, a total of 24 AhMTP genes were identified in peanut, which were divided into seven groups belonging to three substrate-specific clusters (Zn-CDFs, Zn/Fe-CDFs, and Mn-CDFs). All AhMTP genes underwent whole genome or segmental gene duplication events except AhMTP12. Most AhMTP members within the same subfamily or group generally have similar gene and protein structural characteristics. However, some genes, such as AhMTP1.3, AhMTP2.4, and AhMTP12, showed wide divergences. Most of AhMTP genes preferentially expressed in reproductive tissues, suggesting that these genes might play roles in metal transport during the pod and seed development stages. Excess metal exposure induced expressions for most of AhMTP genes in peanut roots depending on cultivars. By contrast, AhMTP genes in the root of Fenghua 1 were more sensitive to excess Fe, Cd, and Zn exposure than that of Silihong. Stepwise linear regression analysis showed that the percentage of Fe in shoots significantly and positively correlated with the expression of AhMTP4.1, AhMTP9.1, and AhMTPC4.1, but negatively correlated with that of AhMTPC2.1 and AhMTP12. The expression of AhMTP1.1 showed a significant and negative correlation with the percentage of Mn in shoots. The percentage of Zn in shoots was significantly and positively correlated with the expression of AhMTP2.1 but was negatively correlated with that of AhMTPC2.1. The differential responses of AhMTP genes to metal exposure might be, at least partially, responsible for the different metal translocation from roots to shoots between Fenghua 1 and Silihong.

ObjectivesHuman leucocyte antigen B27 (HLA-B27) is an important biomarker for ankylosing spondylitis (AS). However, delay in the diagnosis of AS is still common in clinical practice. Several single nucleotide polymorphisms (SNPs) in the coding gene of tumor necrosis factor alpha (TNFα) have been reported to be AS susceptibility loci. Our aim was to explore whether SNPs in TNFα could be used to improve the performance of HLA-B27 for predicting AS.MethodsFive SNPs (rs1799964, rs1800630, rs1799724, rs1800629, and rs361525) spanning TNFα were genotyped by qPCR-Invader assay in 93 AS patients and 107 healthy controls for association analysis and linkage disequilibrium (LD) analysis. Random forest algorithm was utilized to construct the predictive classifiers for AS. HLA-B was genotyped by PCR-sequence-based typing in a subset of the HLA-B27-positive subjects (38 AS patients and 5 healthy controls).ResultsThe T allele of rs1799724 was verified to significantly increase the risk of AS (OR = 4.583, p < 0.0001), while the A allele of rs361525 showed an association with the reduced AS risk (OR = 0.168, p = 0.009). In addition, the rs1799964T-rs1800630C-rs1799724T-rs1800629G-rs361525G haplotype was significantly associated with a higher risk of AS (p < 0.0001). The optimal set of variables for classifiers to predict AS only consisted of HLA-B27. Strong associations with HLA-B27 status were found in both rs1799724 (p < 0.0001) and rs361525 (p = 0.001), and all the analyzed HLA-B27-positive subjects carried HLA-B*27:04 or HLA-B*27:05.ConclusionIn the Chinese Han population, the minor allele T of rs1799724 could increase the risk of AS, while the minor allele A of rs361525 protects individuals from AS. However, the contributions of rs1799724 and rs361525 to AS risk were dependent on HLA-B27 status, suggesting the importance of taking the independence and specificity into consideration in AS susceptibility loci studies.

Graves’ disease (GD), an organ-specific autoimmune disease, is t he most common cause of hyperthyroidism. Tumour necrosis factor-alpha (TNF-α) exhibits immunological and metabolic activities involved in the induction and maintenance of immune responses. We attempted to evaluate the relationship between GD and serum TNF-α and its soluble receptors (sTNFRs), soluble TNF receptor 1 and 2 (sTNF-R1 and s TNF-R2). A total of 72 GD patients and 72 matched healthy individuals were recruited for this study. Serum TNF-α and sTNFRs were measured by sandwich ELISA. In our study, no s ignificant difference was observed in TNF-α, but sTNFRs were found to be significantly elevated in GD patients compared to healthy individuals. Serum sTNFR levels we re positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), and TNF-α was negatively correlated with thyroid-stimulating hormone (TSH) in the GD gro up. It was also shown that thyrotropin receptor antibody (TRAb) was positively correlated with TNF-α and sTNFRs. Spearman’s correlation analysis showed that only sTNF-R1 was po sitively correlated with complement C3. Multiple linear regression analysis suggests tha t serum levels of sTNF-R1 and FT4 may play an important role in the serum level of FT3. A ccording to the median value of FT3 level, GD patients were further divided into a hig h FT3 group and a low FT3 group. The serum levels of sTNF-R1 in the high FT3 GD group wer e significantly higher than those in the low FT3 GD group. In conclusion, sTNFRs may play a n important role in anti-inflammatory and immune response in GD.

We introduce a new R package, BeSS, for solving the best subset selection problem in linear, logistic and Cox's proportional hazard (CoxPH) models. It utilizes a highly efficient active set algorithm based on primal and dual variables, and supports sequential and golden search strategies for best subset selection. We provide a C++ implementation of the algorithm using an Rcpp interface. We demonstrate through numerical experiments based on enormous simulation and real datasets that the new BeSS package has competitive performance compared to other R packages for best subset selection purposes.

Abstract In this paper, we consider the initial boundary value problem for generalized Zakharov equations. Firstly, we prove the existence and uniqueness of the global smooth solution to the problem by a priori integral estimates, the Galerkin method, and compactness theory. Furthermore, we discuss the approximation limit of the global solution when the coefficient of the strong nonlinear term tends to zero.

Objective To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) of patients with non-small cell lung cancer (NSCLC) and their risk of developing brain metastases after adjusting for confounding factors. Methods A retrospective observational study of the general data of patients with NSCLC diagnosed from January 2016 to December 2020. Multivariate logistic regression was used to calculate the dominance ratio (OR) with 95% confidence interval (CI) for NLR and NSCLC brain metastases with subgroup analysis. Generalized summation models and smoothed curve fitting were used to identify whether there was a nonlinear relationship between them. Results In all 3 models, NLR levels were positively correlated with NSCLC brain metastasis (model 1: OR: 1.12, 95% CI: 1.01-1.23, P = .025; model 2: OR: 1.16, 95% CI: 1.04-1.29, P = .007; model 3: OR: 1.20, 95% CI: 1.05-1.37, P = .006). Stratified analysis showed that this positive correlation was present in patients with adenocarcinoma (LUAD) and female patients (LUAD: OR: 1.30, 95% CI: 1.10-1.54, P = .002; female: OR: 1.52, 95% CI: 1.05-2.20, P = .026), while there was no significant correlation in patients with squamous carcinoma (LUSC) and male patients (LUSC: OR:0.76,95% CI:0.38- 1.53, P = .443; male: OR:1.13, 95% CI:0.95-1.33, P = .159). Conclusion This study showed that elevated levels of NLR were independently associated with an increased risk of developing brain metastases in patients with NSCLC, and that this correlation varied by TYPE and SEX, with a significant correlation in female patients and patients with LUAD.

This study aims to understand the influence of COVID-19 on consumers' fears and self-protection motivations. Furthermore, the study seeks to understand the effects of these fears and motivations on consumers' intentions to use omnichannel retailing. A modified theoretical model is proposed by integrating protection motivation theory (PMT) and extending the extended parallel process model (E-EPPM). A total of 398 valid questionnaires are collected and used for further structural equation modeling analysis. The results suggest that the perceived severity, perceived vulnerability, and health anxiety positively impact perceived fears surrounding COVID-19. Furthermore, it is found that perceived fear, self-efficacy, and response efficacy will affect the protection motivation of consumers and ultimately contribute to their behavioral intention to use omnichannel retailing. The findings theoretically enrich the research on COVID-19, PMT, and E-EPPM and empirically provide managerial implications for omnichannel retail service providers.