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Abstract Objective Efgartigimod, a neonatal Fc receptor antagonist, facilitates antibody degradation including pathogenic IgGs. The ADAPT study demonstrated the tolerability and efficacy of efgartigimod in the treatment of generalized myasthenia gravis (gMG). However, very limited evidence is available for the Chinese population, and it remains inconclusive about which kind of patients are selected to preferentially receive efgartigimod in real‐world settings. Methods This multicenter cohort study included gMG patients treated at 14 neuromuscular reference centers in China. The Myasthenia Gravis Activities of Daily Living (MG‐ADL) score, immunosuppressants, and the incidence of treatment‐emergent adverse events (TEAEs) were prospectively collected. Results Of the 1640 gMG admitted between September and December 2023, 61 (3.7%) received efgartigimod for at least one treatment cycle. Among them, 56 cases (92%) were anti‐AChR antibody‐positive, 4 were anti‐MuSK antibody‐positive, and 1 was seronegative. Thymoma‐associated myasthenia gravis accounted for most cases (44%, 27 out of 61). The principal causes of efgartigimod initiation included MG acute exacerbation (MGAE) (48%, 29 out of 61) and myasthenic crisis (MC) (15%, 9 out of 61). Clinically meaningful improvement was rapidly achieved in 97% (58 out of 61) of patients at 1.3 ± 0.7 weeks. By week 12, the MG‐ADL score reduced to 3.8 ± 4.1 (baseline:10.5 ± 5.2) for all participants, while it reduced to 4.0 ± 4.7 for MGAE and 3.8 ± 4.2 for MC, respectively. All but one TMG patient required no additional rescue therapies after efgartigimod initiation. 11.5% (7 out of 61) reported ≥1 TEAEs. Interpretation This multicenter cohort study demonstrated the efficacy of efgartigimod in rapid control of gMG. Patients with MGAE or MC would benefit from efgartigimod treatment.

Abstract Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a urinary disorder that affects youthful to middle-aged men most frequently. It has been revealed that Th17/Treg imbalance is a crucial factor in the pathophysiological mechanisms behind this disease. However, this imbalance’s mechanisms are unknown. In the experimental autoimmune prostatitis (EAP) mouse model, the NLRP3 inflammasome was turned on, IL-1β levels went up. Moreover, there exists a discernible positive association between the upsurge in IL-1β and the perturbation of Th17/Treg equilibrium. Additionally, we have revealed that IL-1β plays a vital role in promoting the differentiation of Naïve CD4+ T cells into the Th17 cells and enhances the conversion of Treg cells into Th17 cells. Further studies revealed that IL-1β promotes STAT3 phosphorylation, which is what causes Treg cells to become Th17 cells. All data strongly suggest that the NLRP3 inflammatory influence Th17 cell development and the conversion of Treg cells into Th17 cells through IL-1β, disrupting the Th17/Treg balance and exacerbating EAP inflammation. In this article, we provide new theories for the pathogenesis of CP/CPPS and propose new prevention and therapy methods.

Abstract Myocardial infarction (MI) has a 5-year mortality rate of more than 50% due to the lack of effective treatments. Interactions between cardiomyocytes and the MI microenvironment (MIM) can determine the progression and fate of infarcted myocardial tissue. Here, a specially designed Melanin-based composite nanomedicines (MCN) is developed to effectively treat MI by reprogramming the MIM. MCN is a nanocomposite composed of polydopamine (P), Prussian blue (PB) and cerium oxide (CexOy) with a Mayuan-like structure, which reprogramming the MIM by the efficient conversion of detrimental substances (H+, reactive oxygen species, and hypoxia) into beneficial status (O2 and H2O). In coronary artery ligation and ischemia reperfusion models of male mice, intravenously injecting MCN specifically targets the damaged area, resulting in restoration of cardiac function. With its promising therapeutic effects, MCN constitutes a new agent for MI treatment and demonstrates potential for clinical application.

Highlights The review provides a comprehensive summary of performance limits of the single two-dimensional transition metal dichalcogenide (2D-TMD) transistor. The review details the two logical expressions of the single 2D-TMD logic transistor, including current and voltage. The review demonstrates the two calculating methods for dynamic energy consumption of 2D synaptic devices.

Abstract 2-Hydroxyacyl-CoA lyase/synthase (HACL/S) is a thiamine diphosphate (ThDP)-dependent versatile enzyme originally discovered in the mammalian α-oxidation pathway. HACL/S natively cleaves 2-hydroxyacyl-CoAs and, in its reverse direction, condenses formyl-CoA with aldehydes or ketones. The one-carbon elongation biochemistry based on HACL/S has enabled the use of molecules derived from greenhouse gases as biomanufacturing feedstocks. We investigated several HACL/S family members with high activity in the condensation of formyl-CoA and aldehydes, and distinct chain-length specificities and kinetic parameters. Our analysis revealed the structures of enzymes in complex with acyl-CoA substrates and products, several covalent intermediates, bound ThDP and ADP, as well as the C-terminal active site region. One of these observed states corresponds to the intermediary α–carbanion with hydroxymethyl-CoA covalently attached to ThDP. This research distinguishes HACL/S from related sub-families and identifies key residues involved in substrate binding and catalysis. These findings expand our knowledge of acyloin-condensation biochemistry and offer attractive prospects for biocatalysis using carbon elongation.

Clostridium perfringens (C. perfringens) is an important veterinary pathogen and a noteworthy threat to human and animal health. Recently, there has been a significant rise in the number of moose fatalities caused by this rare, endemic species in China. Currently, there is an increasing trend in conducting whole-genome analysis of C. perfringens strains originating from pigs and chickens, whereas fewer studies have been undertaken on Elaphurus davidianus-originating strains at the whole-genome level. Our laboratory has identified and isolated five C. perfringens type A from affected Elaphurus davidianus. The current study identified the most potent strain of C. perfringens, which originated from Elaphurus davidianus, and sequenced its genome to reveal virulence genes and pathogenicity. Our findings show that strain CX1-4 exhibits the highest levels of phospholipase activity, hemolytic activity, and mouse toxicity compared to the other four isolated C. perfringens type A strains. The chromosome sequence length of the CX1-4 strain was found to be 3,355,389 bp by complete genome sequencing. The current study unveils the genomic characteristics of C. perfringens type A originating from Elaphurus davidianus. It provides a core foundation for further investigation regarding the prevention and treatment of such infectious diseases in Elaphurus davidianus.

Depression is the most common chronic mental illness and is characterized by low mood, insomnia, and affective disorders. However, its pathologic mechanisms remain unclear. Numerous studies have suggested that the ghrelin/GHSR system may be involved in the pathophysiologic process of depression. Ghrelin plays a dual role in experimental animals, increasing depressed behavior and decreasing anxiety. By combining several neuropeptides and traditional neurotransmitter systems to construct neural networks, this hormone modifies signals connected to depression. The present review focuses on the role of ghrelin in neuritogenesis, astrocyte protection, inflammatory factor production, and endocrine disruption in depression. Furthermore, ghrelin/GHSR can activate multiple signaling pathways, including cAMP/CREB/BDNF, PI3K/Akt, Jak2/STAT3, and p38-MAPK, to produce antidepressant effects, given which it is expected to become a potential therapeutic target for the treatment of depression.

Abstract Slavum lentiscoides and Chaetogeoica ovagalla are two aphid species from the subtribe Fordina of Fordini within the subfamily Eriosomatinae, and they produce galls on their primary host plants Pistacia. We assembled chromosome-level genomes of these two species using Nanopore long-read sequencing and Hi-C technology. A 332 Mb genome assembly of S. lentiscoides with a scaffold N50 of 19.77 Mb, including 11,747 genes, and a 289 Mb genome assembly of C. ovagalla with a scaffold N50 of 11.85 Mb, containing 14,492 genes, were obtained. The Benchmarking Universal Single-Copy Orthologs (BUSCO) benchmark of the two genome assemblies reached 93.7% (91.9% single-copy) and 97.0% (95.3% single-copy), respectively. The high-quality genome assemblies in our study provide valuable resources for future genomic research of galling aphids.

Abstract Background Diabetes-associated cognitive impairment (DACI) poses a significant challenge to the self-management of diabetes, markedly elevating the risk of adverse complications. A burgeoning body of evidence implicates microglia as a central player in the pathogenesis of DACI. Methods We utilized proteomics to identify potential biomarkers in high glucose (HG)-treated microglia, followed by gene knockdown techniques for mechanistic validation in vitro and in vivo. Results Our proteomic analysis identified a significant upregulation of AKAP8L in HG-treated microglia, with concurrent dysregulation of autophagy and inflammation markers, making AKAP8L a novel biomarker of interest. Notably, the accumulation of AKAP8L was specific to HG-treated microglia, with no observed changes in co-cultured astrocytes or neurons, a pattern that was mirrored in streptozotocin (STZ)-induced diabetic mice. Further studies through co-immunoprecipitation and proximity ligation assay indicated that the elevated AKAP8L in HG-treated microglial cells interacts with the mTORC1. In the STZ mouse model, we demonstrated that both AKAP8L knockdown and rapamycin treatment significantly enhanced cognitive function, as evidenced by improved performance in the Morris water maze, and reduced microglial activation. Moreover, these interventions effectively suppressed mTORC1 signaling, normalized autophagic flux, mitigated neuroinflammation, and decreased pyroptosis. Conclusions Our findings highlight the critical role of AKAP8L in the development of DACI. By interacting with mTORC1, AKAP8L appears to obstruct autophagic processes and initiate a cascade of neuroinflammatory responses. The identification of AKAP8L as a key mediator in DACI opens up new avenues for potential therapeutic interventions.

Abstract Background To explore the incidence of chronic endometritis (CE) in patients with infertility and different forms of adenomyosis and analyze potential high-risk factors for infection. Methods This retrospective cohort study included 154 patients with infertility in the Liuzhou Maternity and Child Healthcare Hospital. Among them, 77 patients with adenomyosis were divided into four subgroups based on magnetic resonance imaging (MRI): internal, exterior, intramural, and full-thickness. Meanwhile, 77 patients did not have adenomyosis. Hysteroscopy and endometrial biopsy were performed in the proliferative phase. The main outcome measures were the morphology of the endometrium, syndecan-1 (CD138) immunohistochemical staining, clinical characteristics, and prevalence of CE in the adenomyosis subgroups. Results In comparison to the non-adenomyosis group, the adenomyosis group had significantly higher body mass index (BMI) and CA125 levels. The menstrual cycle in the adenomyosis group was significantly shorter, and menarche was significantly earlier. In comparison to the non-adenomyosis group, the adenomyosis group had a significantly higher diagnostic rate of CE (75.3% vs. 46.8% according to hysteroscopy and 74.0% vs. 33.8% according to histopathology, both with p

Abstract The circular RNA (circRNA) family is a group of endogenous non-coding RNAs (ncRNAs) that have critical functions in multiple physiological and pathological processes, including inflammation, cancer, and cardiovascular diseases. However, their roles in regulating innate immune responses remain unclear. Here, we define Cell division cycle 42 (CDC42)−165aa, a protein encoded by circRNA circCDC42, which is overexpressed in Klebsiella pneumoniae (KP)-infected alveolar macrophages. High levels of CDC42-165aa induces the hyperactivation of Pyrin inflammasomes and aggravates alveolar macrophage pyroptosis, while the inhibition of CDC42-165aa reduces lung injury in mice after KP infection by inhibiting Pyrin inflammasome-mediated pyroptosis. Overall, these results demonstrate that CDC42-165aa stimulates Pyrin inflammasome by inhibiting CDC42 GTPase activation and provides a potential clinical target for pathogenic bacterial infection in clinical practice.

In post-pandemic period of COVID-19, the increase in the number of sub-healthy population, coupled with factors such as global travel, climate change, and increased contact with wildlife, may lead to a rise in the incidence of central nervous system (Central nervous system, CNS) infections by potential zoonotic pathogens, which has become one of the main reasons for the increase in adjusted life years lost due to human disability. Due to the high case fatality rate of CNS infection and the severe sequelae of the body, it is also one of the most serious global public health challenges at present. To resist pathogen invasion, hosts have constructed a series of barrier structures on their surfaces and within their bodies, including skin barrier, blood-lung barrier, blood-testis barrier and blood-brain barrier (BBB). Among these, the BBB is a complex barrier structure composed of various cellular and non-cellular components. As a biological barrier isolating the CNS from the periphery, BBB can prevent a vast majority of harmful substances from entering the brain, thus ensuring the dynamic equilibrium of the brain's internal environment and the normal functioning of the CNS. However, through long-term evolution, pathogens have developed multiple pathways to cross the BBB and invade the CNS. Currently, five invasion pathways have been confirmed by researchers, including infection or disruption of brain endothelial cells; crossing the BBB through transcellular migration; infiltrating through the BBB as a "Trojan horse" via infected leukocytes; entering the CNS through paracellular spaces; and bypassing the BBB and entering the CNS through axonal transport from the periphery. The severity and complexity of CNS infectious diseases are influenced by the nature of the pathogen itself, the structure and function of the host BBB and the diversity of neural invasion pathways. Furthermore, the molecular mechanisms by which pathogens utilize protein interactions, regulate BBB permeability, and invade the CNS through phagocytosis have been elucidated in detail. This has made CNS delivery of certain drugs possible and also laid a theoretical foundation for the development of entirely new CNS drug delivery systems. Therefore, a comprehensive understanding of the structure of the BBB and the pathways through which pathogens invade the CNS will contribute to the development of strategies to control pathogen invasion, novel brain-targeted drugs, and new delivery systems to mitigate established infections in the host CNS.

Grain growth of magnesium (Mg) and its hydride is one of the main reasons for kinetic and capacity degradation during the hydrogen absorption and desorption cycles. To solve this problem, herein we propose a novel method involving synergistic effect of inside embedded metals and outside coated graphene to limit the growth of Mg and its hydride grains. The graphene coated Mg‒Y‒Al alloys were selected as a model system for demonstrating this positive effect where the Mg91Y3Al6 alloy was first prepared by rapidly solidified method and then high-pressure milled with 5 wt% graphene upon 5 MPa hydrogen gas for obtaining in-situ formed YAl2 and YH3 embedded in the MgH2 matrix with graphene shell (denoted as MgH2-Y-Al@GR). In comparison to pure MgH2, the obtained MgH2-Y-Al@GR composites deliver much better kinetics and more stable cyclic performance. For instance, the MgH2-Y-Al@GR can release about 6.1 wt% H2 within 30 min at 300°C but pure MgH2 only desorbs ∼1.5 wt% H2. The activation energy for desorption of MgH2-Y-Al@GR samples is calculated to be 75.3±9.1 kJ/mol that is much lower than approximately 160 kJ/mol for pure MgH2. Moreover, its capacity retention is promoted from ∼57% of pure MgH2 to ∼84% after 50th cycles without obvious particle agglomeration and grain growth. The synergistic effect of outside graphene coating with inside embedded metals which could provide a huge number of active sites for catalysis as well as inhibit the grain growth of Mg and its hydride is believed to be responsible for these.

In radioactivity analysis, counting efficiency(E) and background(to be precise, it should be deterministic background) are usually discussed, but apparent counting efficiency(E') and random background are rarely mentioned. However, the influence of background(including both deterministic background and random background) on apparent counting efficiency must be considered, especially for samples with low radioactivity. The relation between E and E' can be described as the equation E' = E + ΔB/A, where A is the sample radioactivity, and ΔB is the residue background, including two parts: the counting rate of residual deterministic background caused by inaccurate deduction of background and the counting rate of random background that cannot be deducted. In this paper, E' was studied on the following assumptions: E was fixed at 90%; A was changing from 0.1 to 100, with a step of 0.1(relative unit, similarly hereinafter); and ΔB was set to be fixed, or to follow a specific distribution. The simplest continuous distribution(uniform distribution) and the most commonly used continuous distribution(normal distribution) were chosen for this research, and the function “random number generator ” of the software Excel was used to simulate the random variable ΔB. Specifically speaking, the random variable ΔB was assumed to follow ±0.1·U(0,1), ±0.1·U(−0.5,0.5), ±0.1·N(0.5,1), or ±0.1·N(0,1), where U stands for uniform distribution and N for normal distribution. The influence of background on apparent counting efficiencies is divided into two aspects: one is the systematic error introduced by inaccurate background deduction, which makes all apparent counting efficiencies deviate from the counting efficiency in the same direction; the other is the accidental error caused by background fluctuations, which makes apparent counting efficiency fluctuate within a certain range. Regardless of the error type, the influence of background on apparent counting efficiency will increase as the radioactivity of the sample decreases. For samples with high radioactivity, the difference between apparent counting efficiency and counting efficiency is so small that it can be ignored, therefore it is not necessary to distinguish between the two concepts of apparent counting efficiency and counting efficiency; but for samples with low radioactivity, they must be used differently. Unless there is no standard sample with high radioactivity, it is not recommended to use the inefficient method, which is reported in Lin’s paper(ACS Earth Space Chem, 2022, 6(7): 1868-1875), to obtain counting efficiency by measuring a large number of samples with low radioactivity. It is advisable to obtain counting efficiency by measuring standard samples with sufficiently high radioactivity, in which the influence of background can be negligible.

Abstract LIMA1 is a LIM domain and Actin binding 1 protein that acts as a skeleton protein to promote cholesterol absorption, which makes it an ideal target for interfering with lipid metabolism. However, the detailed regulation of LIMA1 remains unclear. Here, we identified that ring finger protein 40 (RNF40), an E3 ubiquitin ligase previously known as an epigenetic modifier to increase H2B ubiquitination, mediated the ubiquitination of LIMA1 and thereby promoted its degradation in a proteasome-dependent manner. Fraction studies revealed that the 1–166aa fragment of LIMA1 was indispensable for the interaction with RNF40, and at least two domains of RNF40 might mediate the association of RNF40 with LIMA1. Notably, treatment with simvastatin dramatically decreased the levels of CHO and TG in control cells rather than cells with overexpressed LIMA1. Moreover, RNF40 significantly decreased lipid content, which could be reversed by LIMA1 overexpression. These findings suggest that E3 ubiquitin ligase RNF40 could directly target LIMA1 and promote its protein degradation in cytoplasm, leading to the suppression of lipid accumulation mediated by LIMA1. Collectively, this study unveils that RNF40 is a novel E3 ubiquitin ligase of LIMA1, which underpins its high therapeutic value to combat dysregulation of lipid metabolism.

Abstract Background Ancient northern East Asians (ANEA) from the Yellow River region, who pioneered millet cultivation, play a crucial role in understanding the origins of ethnolinguistically diverse populations in modern China and the entire landscape of deep genetic structure and variation discovery in modern East Asians. However, the direct links between ANEA and geographically proximate modern populations, as well as the biological adaptive processes involved, remain poorly understood. Results Here, we generated genome-wide SNP data for 264 individuals from geographically different Han populations in Shandong. An integrated genomic resource encompassing both modern and ancient East Asians was compiled to examine fine-scale population admixture scenarios and adaptive traits. The reconstruction of demographic history and hierarchical clustering patterns revealed that individuals from the Shandong Peninsula share a close genetic affinity with ANEA, indicating long-term genetic continuity and mobility in the lower Yellow River basin since the early Neolithic period. Biological adaptive signatures, including those related to immune and metabolic pathways, were identified through analyses of haplotype homozygosity and allele frequency spectra. These signatures are linked to complex traits such as height and body mass index, which may be associated with adaptations to cold environments, dietary practices, and pathogen exposure. Additionally, allele frequency trajectories over time and a haplotype network of two highly differentiated genes, ABCC11 and SLC10A1, were delineated. These genes, which are associated with axillary odor and bilirubin metabolism, respectively, illustrate how local adaptations can influence the diversification of traits in East Asians. Conclusions Our findings provide a comprehensive genomic dataset that elucidates the fine-scale genetic history and evolutionary trajectory of natural selection signals and disease susceptibility in Han Chinese populations. This study serves as a paradigm for integrating spatiotemporally diverse ancient genomes in the era of population genomic medicine.

Abstract Invasive pests reduce biodiversity and ecosystem service functions, thereby leading to economic and also agricultural losses. Banana skipper (Erionota torus Evans), red palm weevil (Rhynchophorus ferrugineus), and coconut caterpillar (Opisina arenosella Walker) are invasive insect pests in the palm-growing regions and they have had serious consequences for the planting of bananas (Musa nana), palms (Trachycarpus fortune) and coconut (Cocos nucifera). Based on screened occurrence data, the present research utilized Maximum Entropy model (Maxent) to simulate the distribution dynamics of these three invasive insects in China, under current and future climate (2050s, 2070s, 2090s) in two shared socio-economic pathways (SSPs: 126 and 585) of the newly released coupled model intercomparison project phase6 (CMIP6). The results show that: (1) Under current and future climate conditions, all model groups exhibited an AUC value exceeding 0.92, which shows that the model prediction results are very good;(2) The suitable habitat area of E. torus Evans remains relatively stable with some expansion in the SSP126 of 2090s and some contraction in the SSP585 of 2090s. The suitable habitat area of R. ferrugineus showed an overall contraction, with substantial contraction in the SSP585 of 2090s.The suitable habitat area of O. arenosella has an overall expansion, with the most pronounced expansion in the SSP585 of 2070s; (3) The current centroid of suitable habitats for R. ferrugineus and E. torus Evans is located in Guangxi Province and wholely shift toward the south direction under future climate. The centroid of suitable habitats for O. arenosella is currently located in the northeastern maritime area of Hainan Province and will shift toward the north direction under future climate; (4) Temperature, precipitation and Human disturbance factors (Population density and Human influence index) were crucial variables for describing the distribution of the three species. For E. torus Evans in particular, percentage contributions of Population density was up to 31.4, which is only 0.1 different from ranked first Bio19 (Precipitation of the coldest quarter). The dynamics of habitats of these three species and the correlating driver factors proposed in this work provide essential insights into future spatial management of the three invasive insects in China. Our work is necessary and timely in identifying newly areas at high risk of expansion of the three invasive insects in the future, then suggesting strategic control measures to prevent their spread, and finally providing scientific evidence for the early prevention and rapid response to the three invasive insects.

Abstract Background Esophageal cancer, a global health concern, impacts predominantly men, particularly in Eastern Asia. Lymph node metastasis (LNM) significantly influences prognosis, and current imaging methods exhibit limitations in accurate detection. The integration of radiomics, an artificial intelligence (AI) driven approach in medical imaging, offers a transformative potential. This meta-analysis evaluates existing evidence on the accuracy of radiomics models for predicting LNM in esophageal cancer. Methods We conducted a systematic review following PRISMA 2020 guidelines, searching Embase, PubMed, and Web of Science for English-language studies up to November 16, 2023. Inclusion criteria focused on preoperatively diagnosed esophageal cancer patients with radiomics predicting LNM before treatment. Exclusion criteria were applied, including non-English studies and those lacking sufficient data or separate validation cohorts. Data extraction encompassed study characteristics and radiomics technical details. Quality assessment employed modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Radiomics Quality Score (RQS) tools. Statistical analysis involved random-effects models for pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC). Heterogeneity and publication bias were assessed using Deek’s test and funnel plots. Analysis was performed using Stata version 17.0 and meta-DiSc. Results Out of 426 initially identified citations, nine studies met inclusion criteria, encompassing 719 patients. These retrospective studies utilized CT, PET, and MRI imaging modalities, predominantly conducted in China. Two studies employed deep learning-based radiomics. Quality assessment revealed acceptable QUADAS-2 scores. RQS scores ranged from 9 to 14, averaging 12.78. The diagnostic meta-analysis yielded a pooled sensitivity, specificity, and AUC of 0.72, 0.76, and 0.74, respectively, representing fair diagnostic performance. Meta-regression identified the use of combined models as a significant contributor to heterogeneity (p-value = 0.05). Other factors, such as sample size (> 75) and least absolute shrinkage and selection operator (LASSO) usage for feature extraction, showed potential influence but lacked statistical significance (0.05

Abstract Background Kidney transplant recipients (KTRs) are at an elevated risk of progressing to severe infections upon contracting COVID-19. We conducted a study on risk factors and multi-pathogen infections in KTRs with SARS-CoV-2 Omicron variant. Methods KTRs were subjected to a thorough etiological evaluation. Whenever feasible, they were also provided with bronchoscopy and bronchoalveolar lavage to enable metagenomic next-generation sequencing (mNGS), ideally within a 48-hour window post-admission. We performed a retrospective analysis for pathogens and risk factors of KTRs with the COVID-19 virus variant Omicron. Results We included thirty patients in our study, with sixteen exhibiting single infection of COVID-19 and fourteen experiencing co-infections, predominantly with Pneumocystis jirovecii. Notably, patients with severe cases demonstrated significantly elevated levels of C-reactive protein (CRP) and interleukin-6 compared to those with moderate cases (P

Abstract Background The period of standardized training is a transitional stage when Generation Z newly graduated registered nurses (Gen Z NGRNs) change their role from student to nurse. Affected by the COVID-19, they lack clinical practice and practicum experience in emergency departments in their university studies. At the beginning of career, they are under great pressure. Resilience is one of the factors that reduce their stress level and increases endurance. It is of interest to understand how this representative group of nurses gained and played the experience of resilience early in their careers. Objective To explore Gen Z NGRNs’ experience and process of resilience, to provide a new perspective and theoretical basis for psychological rehabilitation or intervention of medical staff who experienced transition shock. Methods This study employed a qualitative design based on the phenomenological approach. 18 nurses from a third-level class-A hospital in Shanghai who participated in standardized training in emergency department were enrolled using purposive sampling. Data collection was through in-depth and semi-structured interviews and continued until reaching data saturation. Results The investigation uncovered three themes and ten subthemes. Pressure and challenge contained high workload and high risk coexist, death’s stress response, more emergencies and high professional requirements. Coping and adaptation contained team help, psychological restructuring, peer support, transformational leadership. Reflection and planning contained enhance learning, appreciate life. Conclusions Our study described the embodiment and coping experience of the physical and mental stress faced by Gen Z NGRNs during their standardized training in the emergency department. It is emphasized that nurse educators should pay attention to the character and actual needs of Gen Z NGRNs, explore and formulate strategies, so as to guide NGRNs to quickly adapt and grow in the new role. The ultimate goal is to increase nurse retention and improve the quality of nursing.

Abstract Objective To analyze the clinical characteristics of esophageal button battery impactions in children and explore safe and effective treatment methods. Methods This retrospective cohort study was conducted at a single tertiary care center, Shenzhen Children’s Hospital, encompassing 89 children diagnosed with esophageal button battery impactions between January 2013 and January 2023. To minimize esophageal mucosal corrosion, prompt removal of the button battery with a first-aid fast track rigid esophagoscopy under general anesthesia was performed within thirty minutes of diagnosis. The clinical features and complications were recorded and analyzed. Results Button battery as esophageal foreign body was prevalent among children under 3 years old (79.8%), with boys exhibiting a higher incidence rate (56.2%) compared to girls (43.8%), and an average age of 25.8 months. The median duration from ingestion to hospital admission was 3 h (range: 0.5 h to 3 months). Common symptoms included vomiting and dysphagia, with early stage vomiting of brown foamy secretions being a characteristic presentation of esophageal button battery impactions. The majority (77.5%) of batteries were lodged in the upper esophagus. The larger batteries were verified to be more prone to complications. All 89 cases exhibited varying degrees of esophageal mucosal erosion, with 31 cases (34.8%) experiencing severe complications, including esophageal stenosis in 11 cases (35.5%), esophageal perforation in 9 cases (29%) with 4 cases of tracheoesophageal fistula, vocal cord paralysis in 6 cases (19.4%), hemorrhage in 2 cases (6.5%), mediastinitis in 2 cases (6.5%), and periesophageal abscess in 1 case (3.2%). Despite the severity of these complications, none of the patients died after emergency surgery. Conclusion Esophageal button battery impactions can lead to significant damage to the esophageal mucosa due to its strong corrosiveness. Prompt action is crucial to mitigate the risk of complications. For the first time, we implement a first-aid fast track surgical intervention following diagnosis is imperative to minimize the incidence of adverse outcomes.

Abstract Titanium (Ti) dental scaffolds are widely used in dental prosthetics due to their excellent mechanical properties and biocompatibility. However, conventional Ti scaffolds manufactured through machining often do not fit perfectly with the bone defect site. Laser powder bed fusion (LPBF) technology enables the personalised manufacturing of custom‐made Ti scaffolds. A custom‐made Ti scaffold was prepared using LPBF and its surface roughness was improved through chemical polishing. To enhance the surface roughness, a nitric acid mixed solution with a specific composition of HF: HNO3:C3H6O3 = 2:2:3 was used. The polishing mechanism was investigated by adjusting the F/Ti ratio to control the formation and dissolution of the oxide film. As a result, the surface of the Ti scaffold after polishing exhibited a smooth and flat appearance compared to the LPBF part, with a reduced surface roughness (Ra) of 1.23 ± 0.19 μm. The custom‐made Ti scaffold also demonstrated favourable mechanical properties, with a bending strength of 335.18 ± 33.62 MPa and stiffness of 2.13 ± 0.21 GPa. Furthermore, in vitro cell tests confirmed the excellent biocompatibility of the custom‐made Ti scaffold. The authors present a feasible strategy for the further clinical application of custom‐made Ti scaffolds, offering enhanced surface properties and addressing the limitations of conventional machining methods.

C21H20Cl2N2O2, orthorhombic, P21 (no. 4), a = 8.3667(14) Å, b = 15.444(3) Å, c = 15.105(2) Å, V = 1951.9(6) Å3, Z = 4, Rgt (F) = 0.0481, wRref (F 2) = 0.1574, T = 292 K.

C21H25N3O2, triclinic, P1̄ (no. 2), a = 7.6536(6) Å, b = 11.027(1) Å, c = 12.6899(11) Å, α = 66.863(2)°, β = 80.598(2)°, γ = 71.772(2)°, V = 934.38(14) Å3, Z = 2, R gt(F) = 0.0679, wR ref(F 2) = 0.1150, T = 296 K.

The commercially available drug-eluting stent with limus (rapamycin, everolimus, etc.) or paclitaxel inhibits smooth muscle cell (SMC), reducing the in-stent restenosis, whereas damages endothelial cell (EC) and delays stent reendothelialization, increasing the risk of stent thrombosis (ST) and sudden cardiac death. Here we present a new strategy for promoting stent reendothelialization and preventing ST by exploring the application of precise molecular targets with EC specificity. Proteomics was used to investigate the molecular mechanism of EC injury caused by rapamycin. Endothelial protein C receptor (EPCR) was screened out as a crucial EC-specific effector. Limus and paclitaxel repressed the EPCR expression, while overexpression of EPCR protected EC from coating (eluting) drug-induced injury. Furthermore, the ligand activated protein C (APC), polypeptide TR47, and compound parmodulin 2, which activated the target EPCR, promoted EC functions and inhibited platelet or neutrophil adhesion, and enhanced rapamycin stent reendothelialization in the simulated stent environment and in vitro. In vivo, the APC/rapamycin-coating promoted reendothelialization rapidly and prevented ST more effectively than rapamycin-coating alone, in both traditional metal stents and biodegradable stents. Additionally, overexpression or activation of the target EPCR did not affect the cellular behavior of SMC or the inhibitory effect of rapamycin on SMC. In conclusion, EPCR is a promising therapeutical agonistic target for pro-reendothelialization and anti-thrombosis of eluting stent. Activation of EPCR protects against coating drugs-induced EC injury, inflammatory cell, or platelet adhesion onto the stent. The novel application formula for APC/rapamycin-combined eluting promotes stent reendothelialization and prevents ST.

In order to solve the problem of poor performance of welded joints of steel and aluminum dissimilar materials, this study proposes the use of ceramic particle-reinforced aluminum alloy as an alternative to traditional aluminum alloy for welding, effectively overcoming this problem. In this paper, the laser welding of stainless steel/6061 aluminum alloy (SA) and stainless steel/TiC–TiB2 duplex nanoparticle-reinforced 6061 aluminum alloy (SRA) was realized. The effect of ceramic nanoparticles on the microstructure and mechanical properties of SRA joint was systematically studied, and the strengthening mechanism of nanoparticles was revealed. Under the same process parameters, the melting zone of SRA joint is larger and the intermetallic compound (IMCs) layer is narrower. Moreover, the grain size of the brittle Fe–Al compound phase in the IMCs layer is significantly reduced, which effectively inhibits the initiation of cracks at the steel/aluminum interface. The study shows that ceramic particles have a pinning effect on the dislocations, limiting the grain growth, reducing the thickness of the intermetallic compound layer, and decreasing the content of the brittle FeAl3 phase. Moreover, ceramic nanoparticles promote the formation of Mg2Si strengthened phase at the grain boundary, further hinder the dislocation movement and improve the strength of the joint. Under the welding power of 3400 W and welding speed of 31 mm/s, SRA joint achieves the maximum tensile shear of 1718 N, which is 15% higher than the strength of SA joint.

A novel coated urea (MVCU) was prepared, and its application effect was verified by field trials of oilseed rape in three main cultivation areas. Meanwhile, the nutrient release and coating layer changes of MVCU in static water at 25 °C and different soils were systematically evaluated. MVCU showed a long nutrient release time under static water (77 days) and soil incubation (140 days) conditions due to the slow degradation of the coating layer in MVCU, and its nitrogen release coincided well with oilseed rape nitrogen demand. The above results were further confirmed by FT-IR spectra and SEM analysis. Compared with conventional urea (U), the field trials of MVCU in the three main cultivation areas showed high nitrogen utilization efficiency and yield advantages in oilseed rape. The field trials results indicated that the MVCU significantly enhanced the aboveground dry matter (28.7%), the seed nitrogen concentration (9.5%) and aboveground nitrogen accumulation (42.5%) of oilseed rape at the mature stage as compared to that of the U. The oilseed rape yield enhanced by 932.8 kg/hm2, the average growth rate was 65.1%, and nitrogen utilization efficiency increased by 21.2%. In short, MVCU has the advantages of excellent slow-release performance and strong applicability, and its yield-increasing effect on oilseed rape could reach or even be better than that of traditional fertilization.

Objective: To assess if there is a relationship between residential radon exposure and two lung cancer histological types, small-cell carcinoma (diagnosed in people with a smoking history) and adenocarcinoma (the most commonly diagnosed histologic type in people who have never smoked) among males and females in Canada. Methods: With survey data of long-term radon measurements in residential homes, long-term averaged tobacco consumption rates in the units of cigarettes per day per person and long-term averaged age-standardized lung cancer incidence rates at provincial level, simple linear fitting (ANOVA linear regression) was applied in this study to determine the effect on lung cancer induction by smoking and exposure to indoor radon, and to assess if there is a relationship between residential radon exposure and lung cancer histological types. Results: Lung cancer incidence rates correlate very well with the tobacco consumption rates (P ​

Immunosuppression tumor microenvironment (TME) seriously impedes anti-tumor immune response, resulting in poor immunotherapy effect of cancer. This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells, resulting in high CKb11 secretion from tumor cells, successfully activating immune cells and increasing cytokine secretion to reshape the TME, and ultimately delaying tumor progression. The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME. It can cause high expression of IFN-γ, which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor cells. Therefore, combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense, leading to a collaborative anti-tumor outcome. Thus, utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites, thereby reshaping immunosuppressive TME for cancer treatment, has great potential as an immunogene therapy in clinical applications.

【Objective】Rice blast resistance genes Pi2 and Pita are broad-spectrum resistance genes to rice blast in rice areas in South China, which have very important application value for rice blast resistance breeding. Therefore, the development of a set of efficient identification methods is beneficial to genetic breeding efficiency of rice blast-resistant varieties.【Method】According to the variant GCA GGA/GTG TTA of the 787 and 788 codons of the Pi2 gene in 'Huanghuangyouzhan' (highly resistant to rice blast) and 'Guangluai 4' (highly susceptible to rice blast), and the variant G/T at base 6 640 of Pita gene in Tetp (an international rice germplasm resource with high resistance to rice blast) and Lijiang Xintuan Heigu (a local ermplasm resource with high susceptibility to rice blast), based on the competitive allele PCR (Kompetitive Allele Specific PCR, KASP) labeling technology principle, molecular markers of rice blast resistance genes were developed.【Result】Two KASP markers (W-Pi2 and W-Pita) were developed to detect the functional sites of Pi2 and Pita. The markers were used to detect the conventional rice, aromatic rice and hybrid rice cultivated by the Rice Research Institute of Guangdong Academy of Agricultural Sciences. 19 resistant varieties were screened, including 13 varieties with a single gene tested as a diseaseresistant allele and 6 varieties with two genes tested as disease-resistant alleles. The comparison of the two markers suggested that the frequency of disease-resistance was higher in the varieties carrying Pi2 resistance gene than in the varieties carrying Pita resistance gene. The results showed that the two markers could detect the allele types of rice blast resistance genes Pi2 and Pita in breeding materials in the early stage (seed or seedling stage), and the breeding materials were not required to be planted in the disease nursery, then individual plants carrying resistant alleles could be screened and identified.【Conclusion】The developed KASP functional molecular markers W-Pi2 and W-Pita can better distinguish parental varieties with different resistance, clearly distinguish different allele types among breeding materials, and accurately screen breeding materials.

High-purity tantalum is used as the sputtering target material for integrated circuits, requiring fine grains and random texture. Understanding different orientation deformation mechanisms, especially the metastable orientation (here {112} crystallographic orientations), is beneficial for controlling the structure of tantalum target materials. This paper employs EBSD and crystallographic calculations to regulate the grain deformation behavior by introducing a reverse strain at 135° clock rolling. The deformation behavior and dislocation density distribution of the metastable oriented grains under different strain paths are quantitatively analyzed. Results show that unidirectional rolling (UR) generates stress concentration, causing an uneven distribution of geometrically necessary dislocation density. The splitting behavior of {112} and {111} grains is promoted, and they have similar deformation behavior in UR process, while the deformation of {100} oriented grains is significantly suppressed. Furthermore, changing the strain path promotes the splitting of {100} grains, and makes the {112} change from the soft orientation to the hard orientation. This change makes it easier to start multi-slipping, resulting in a more uniform deformation. Additionally, crystallographic calculations show that Schmid factor is ineffective in explaining the strain localization problem in BCC metals. However, Schmid factor difference ratio makes it possible to analyze the distribution of dislocation density in local regions through the quantitative calculation of multi-slipping.

Abstract Background Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies. Methods Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2–4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker. Results Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35–2.66) for C-Alb, and 1.89 [1.27–2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10–1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707–0.743] with C-Alb and 0.725 [0.707–0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics. Conclusions C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.

Abstract Peanut (Arachis hypogaea L.) is an important oilseed crop worldwide. However, soil salinization becomes one of the main limiting factors of peanut production. Therefore, developing salt-tolerant varieties and understanding the molecular mechanisms of salt tolerance is important to protect peanut yield in saline areas. In this study, we selected four peanut varieties with contrasting response to salt challenges with T1 and T2 being tolerance and S1 and S2 being susceptible. High-throughput RNA sequencing resulted in more than 314.63 Gb of clean data from 48 samples. We identified 12,057 new genes, 7,971of which have functional annotations. KEGG pathway enrichment analysis of uniquely expressed genes in salt-tolerant peanut revealed that upregulated genes in the root are involved in the MAPK signaling pathway, fatty acid degradation, glycolysis/gluconeogenesis, and upregulated genes in the shoot were involved in plant hormone signal transduction and the MAPK signaling pathway. Na+ content, K+ content, K+/ Na+, and dry mass were measured in root and shoot tissues, and two gene co-expression networks were constructed based on weighted gene co-expression network analysis (WGCNA) in root and shoot. In this study, four key modules that are highly related to peanut salt tolerance in root and shoot were identified, plant hormone signal transduction, phenylpropanoid biosynthesis, starch and sucrose metabolism, flavonoid biosynthesis, carbon metabolism were identified as the key biological processes and metabolic pathways for improving peanut salt tolerance. The hub genes include genes encoding ion transport (such as HAK8, CNGCs, NHX, NCL1) protein, aquaporin protein, CIPK11 (CBL-interacting serine/threonine-protein kinase 11), LEA5 (late embryogenesis abundant protein), POD3 (peroxidase 3), transcription factor, and MAPKKK3. There were some new salt-tolerant genes identified in peanut, including cytochrome P450, vinorine synthase, sugar transport protein 13, NPF 4.5, IAA14, zinc finger CCCH domain-containing protein 62, beta-amylase, fatty acyl-CoA reductase 3, MLO-like protein 6, G-type lectin S-receptor-like serine/threonine-protein kinase, and kinesin-like protein KIN-7B. The identification of key modules, biological pathways, and hub genes in this study enhances our understanding of the molecular mechanisms underlying salt tolerance in peanuts. This knowledge lays a theoretical foundation for improving and innovating salt-tolerant peanut germplasm.

Abstract Background To explore a method for screening and diagnosing neonatal congenital heart disease (CHD) applicable to grassroots level, evaluate the prevalence of CHD, and establish a hierarchical management system for CHD screening and treatment at the grassroots level. Methods A total of 24,253 newborns born in Tang County between January 2016 and December 2020 were consecutively enrolled and screened by trained primary physicians via the “twelve-section ultrasonic screening and diagnosis method” (referred to as the “twelve-section method”). Specialized staff from the CHD Screening and Diagnosis Center of Hebei Children’s Hospital regularly visited the local area for definite diagnosis of CHD in newborns who screened positive. Newborns with CHD were managed according to the hierarchical management system. Results The centre confirmed that, except for 2 newborns with patent ductus arteriosus missed in the diagnosis of ventricular septal defect combined with severe pulmonary hypertension, newborns with other isolated or concomitant simple CHDs were identified at the grassroots level. The sensitivity, specificity and diagnostic coincidence rate of the twelve-section method for screening complex CHD were 92%, 99.6% and 84%, respectively. A total of 301 children with CHD were identified. The overall CHD prevalence was 12.4‰. According to the hierarchical management system, 113 patients with simple CHD recovered spontaneously during local follow-up, 48 patients continued local follow-up, 106 patients were referred to the centre for surgery (including 17 patients with severe CHD and 89 patients with progressive CHD), 1 patient died without surgery, and 8 patients were lost to follow-up. Eighteen patients with complex CHD were directly referred to the centre for surgery, 3 patients died without surgery, and 4 patients were lost to follow-up. Most patients who received early intervention achieved satisfactory results. The mortality rate of CHD was approximately 28.86 per 100,000 children. Conclusions The “twelve-section method” is suitable for screening neonatal CHD at the grassroots level. The establishment of a hierarchical management system for CHD screening and treatment is conducive to the scientific management of CHD, which has important clinical and social significance for early detection, early intervention, reduction in mortality and improvement of the prognosis of complex and severe CHDs.

Abstract This paper proposes and investigates a novel 4H‐SiC trench MOSFET (TMOS) with integrated high‐K deep trench and gate dielectric (INHK‐TMOS). The integrated high‐K (INHK) consists of a high‐K gate dielectric and an extended high‐K deep trench dielectric in the drift region. Firstly, the high‐K gate dielectric together with the metal‐forming high‐K metal gate structure, which increases the gate oxide capacitance (COX), reduces the threshold voltage (VTH) and the specific on‐resistance (Ron,sp). Secondly, the extended high‐K deep trench dielectric not only modulates the electric field in the drift region by introducing a new electric field peak at the bottom of the high‐K deep trench dielectric, thereby enhancing the breakdown voltage (BV), but also improves the doping concentration (ND) of the drift region by the assist depletion effect of the high‐K dielectric, further optimizing the forward conduction characteristics. Simulation results demonstrate that when compared to the conventional TMOS, the INHK‐TMOS using HfO2 exhibits a 52.6% reduction in VTH, a 52.1% reduction in Ron,sp, a 20.3% increasement in BV and a 202.3% improvement in figure of merit.

Purpose This cross-sectional cohort-comparison observational study investigated the value of high-frame-rate vector flow (V Flow) imaging for evaluating differences in carotid plaque shape and biomechanical parameters in patients with mild stenosis according to a recent history of ipsilateral ischemic stroke. Methods The present study included 352 patients from February 2023 to October 2023, who were categorized as symptomatic or asymptomatic based on a history of recent ischemic stroke and ipsilateral ischemic lesions detected on head computed tomography or magnetic resonance imaging. A Mindray Resona R9 system was used for B-mode ultrasonography and V Flow imaging. The upstream and downstream surfaces of the plaques were examined at the carotid bifurcation for wall shear stress (WSS), oscillatory shear index (OSI), and turbulence index, which performed peri-plaque biomechanical condition. Multivariable logistic regression models were used to determine associations between plaque shape, V Flow parameters, and ischemic stroke. Results Symptomatic patients exhibited higher WSS values for the upstream and downstream surfaces of carotid plaque, as well as higher OSI and turbulence index values for the downstream surface. Type Ⅲ plaques and higher WSS and OSI values for the downstream surface of the plaque were significantly associated with ischemic stroke. Type Ⅲ plaques were more prevalent in symptomatic patients and demonstrated much higher WSS and OSI values for the downstream plaque surface in both groups. Conclusion High-frame-rate V Flow imaging could assess peri-plaque biomechanical forces and may provide effective imaging biomarkers for early prediction of ischemic stroke in patients with mild stenosis.

Abstract Wogonin is a natural flavone compound from the plant Scutellaria baicalensis, which has a variety of pharmacological activities such as anti-cancer, anti-virus, anti-inflammatory, and immune regulation. However, the potential mechanism of wogonin remains unknown. This study was to confirm the molecular mechanism of wogonin for acute monocytic leukemia treatment, known as AML-M5. The potential action targets between wogonin and acute monocytic leukemia were predicted from databases. The compound-target-pathway network and protein-protein interaction network (PPI) were constructed. The enrichment analysis of related targets and molecular docking were performed. The network pharmacological results of wogonin for AML-M5 treatment were verified using the THP-1 cell line. 71 target genes of wogonin associated with AML-M5 were found. The key genes TP53, SRC, AKT1, RELA, HSP90AA1, JUN, PIK3R1, and CCND1 were preliminarily found to be the potential central targets of wogonin for AML-M5 treatment. The PPI network analysis, GO analysis and KEGG pathway enrichment analysis demonstrated that the PI3K/AKT signaling pathway was the significant pathway in the wogonin for AML-M5 treatment. The antiproliferative effects of wogonin on THP-1 cells of AML-M5 presented a dose-dependent and time-dependent manner, inducing apoptosis, blocking the cell cycle at the G2/M phase, decreasing the expressions of CCND1, CDK2, and CyclinA2 mRNA, as well as AKT and p-AKT proteins. The mechanisms of wogonin on AML-M5 treatment may be associated with inhibiting cell proliferation and regulating the cell cycle via the PI3K/AKT signaling pathway.

Abstract Assessing groundwater quality is critical to regional water resource conservation and human health safety, especially in areas with co-existence of toxic constituents fluoride (F−) and arsenic (As). In this study, fourteen groundwater samples were collected in Feng County, Northwestern Jiangsu Province to identify dominant contaminants and their spatial distribution and health risk. The composition and variation characteristics of major ions (K+, Na+, Ca2+, Mg2+, Cl−, SO4 2−, HCO3 −, and NO3 −) and trace elements (F−, As, and Mn) were analyzed. The hydrochemical results revealed that high F− groundwater was mainly distributed in the northern areas whereas As-riched groundwater was primarily distributed in southern areas. Notably, over 85.7% and 21.4% of the shallow groundwater samples exceeded the drinking water quality standard of 1.5 mg/L for F− and 10 µg/L for As, respectively. Based on the water quality index (WQI) appraisal result, 71.4% of the groundwater in the study area is classified as “poor”, and thus unsuitable for drinking directly. We assessed the human non-carcinogenic health risk of F− (HQFluoride) and As (HQArsenic) and the carcinogenic health risk of As (CRArsenic). The calculated hazard quotient (HQ) for F− indicated nearly all groundwater samples have an unacceptable risk (HQ > 1) for each age group. However, HQArsenic values revealed that 28.6%, 21.4%, 21.4%, and 21.4% of groundwater samples posed potential non-carcinogenic health risks for infants, children, females, and males, respectively. The calculated results of CRArsenic showed that 0%, 21.4%, 28.6%, and 28.6% of groundwater samples posed unacceptable health risks (CR > 1.0 × 10−4) to infants, children, females, and males, respectively. The groundwater irrigation suitability assessment results showed that 21.4% of samples were doubtful to unsuitable for irrigation, and 85.7% owed magnesium hazards. The findings of this study will assist policymakers in formulating proper remedial policies and mitigation strategies to ensure the safety of drinking and irrigation water.

The rise of e-commerce, bolstered by advancements in information and communication technology (ICT), has made it possible for consumers to shop online without the need to physically travel. The unexpected emergence of COVID-19 further accelerated this shift towards online shopping. This paper delves into the nuances of virtual versus physical access to goods, drawing from the dual access theory. It aims to offer a comprehensive understanding of the disparities in accessibility between digital and brick-and-mortar shopping experiences. Our results indicate that when considering the complete private costs—including the intrinsic costs of shopping and those incurred en route like travel and delivery fees—online shopping typically offers greater accessibility and is more cost-effective than its in-store counterpart. Interestingly, while physical access to shopping displays a pattern where the central city has a distinct advantage over the suburbs, virtual access presents a more uniform distribution throughout the city.

Abstract Background Clinically, most patients with Kaposi's sarcoma (KS) are male, and several direct and indirect mechanisms may underlie this increased susceptibility in men, Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is considered to be the primary etiological agent responsible for KS. Thus, we propose the hypothesis that men are more susceptible to HHV-8 infection, leading to a higher incidence of Kaposi's sarcoma among males. A meta-analysis was conducted to evaluate the association between gender and HHV-8 seropositivity in the general population. Methods A comprehensive literature search was performed using 6 online databases: PubMed, EMBASE, Cochrane library, Web of Science, CNKI, and Wanfang. Studies published before March 15, 2023, were included. Results In all, 33 articles including 41 studies were included in the meta-analysis. In the included adult population. men had a higher risk of HHV-8 infection than did women in adult populations from all over the world (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.01–1.15), but no differences were found in child population from all over the world (OR: 0.90, 95% CI: 0.79–1.01). There was a significant difference in HHV-8 seroprevalence between men and women in sub-Saharan Africa (SSA) adult population (OR: 1.15, 95% CI: 1.05–1.26). However, no significant differences were observed in sub-Saharan Africa (SSA) child population (OR: 0.90, 95%CI 0.78–1.03). As for other continents, the results showed no significant difference, such as the Asian population (OR: 1.03, 95%CI: 0.92–1.16). or the European and American populations (OR 1.01, 95%CI 0.87–1.17). Conclusion There was a slight gender disparity for HHV-8 infection in the adult population. Among the adult populations from SSA and globally, men were more likely to be infected with HHV-8 than were women. However, no statistical significance was observed in the child populations from SSA and globally. In the future, the inclusion of more standardized studies may strengthen the results of this study.

Abstract The High Average Utility Itemset Mining (HAUIM) technique, a variation of High Utility Itemset Mining (HUIM), uses the average utility of the itemsets. Historically, most HAUIM algorithms were designed for static databases. However, practical applications like market basket analysis and business decision-making necessitate regular updates of the database with new transactions. As a result, researchers have developed incremental HAUIM (iHAUIM) algorithms to identify HAUIs in a dynamically updated database. Contrary to conventional methods that begin from scratch, the iHAUIM algorithm facilitates incremental changes and outputs, thereby reducing the cost of discovery. This paper provides a comprehensive review of the state-of-the-art iHAUIM algorithms, analyzing their unique characteristics and advantages. First, we explain the concept of iHAUIM, providing formulas and real-world examples for a more in-depth understanding. Subsequently, we categorize and discuss the key technologies used by varying types of iHAUIM algorithms, encompassing Apriori-based, Tree-based, and Utility-list-based techniques. Moreover, we conduct a critical analysis of each mining method's advantages and disadvantages. In conclusion, we explore potential future directions, research opportunities, and various extensions of the iHAUIM algorithm.

Abstract Liver fibrosis, as a consequence of chronic liver disease, involves the activation of hepatic stellate cell (HSC) caused by various chronic liver injuries. Emerging evidence suggests that activation of HSC during an inflammatory state can lead to abnormal accumulation of extracellular matrix (ECM). Investigating novel strategies to inhibit HSC activation and proliferation holds significant importance for the treatment of liver fibrosis. As a member of the doublecortin domain-containing family, doublecortin domain containing 2 (DCDC2) mutations can lead to neonatal sclerosing cholangitis, but its involvement in liver fibrosis remains unclear. Therefore, this study aims to elucidate the role of DCDC2 in liver fibrosis. Our findings revealed a reduction in DCDC2 expression in both human fibrotic liver tissues and carbon tetrachloride (CCl4)-induced mouse liver fibrotic tissues. Furthermore, exposure to transforming growth factor beta-1(TGF-β1) stimulation resulted in a dose- and time-dependent decrease in DCDC2 expression. The overexpression of DCDC2 inhibited the expression of α-smooth muscle actin (α-SMA) and type I collagen alpha 1 (Col1α1), and reduced the activation of HSC stimulated with TGF-β1. Additionally, we provided evidence that the Wnt/β-catenin signaling pathway was involved in this process, wherein DCDC2 was observed to inhibit β-catenin activation, thereby preventing its nuclear translocation. Furthermore, our findings demonstrated that DCDC2 could attenuate the proliferation and epithelial-mesenchymal transition (EMT)-like processes of HSC. In vivo, exogenous DCDC2 could ameliorate CCl4-induced liver fibrosis. In summary, DCDC2 was remarkably downregulated in liver fibrotic tissues of both humans and mice, as well as in TGF-β1-activated HSC. DCDC2 inhibited the activation of HSC induced by TGF-β1 in vitro and fibrogenic changes in vivo, suggesting that it is a promising therapeutic target for liver fibrosis and warrants further investigation in clinical practice.

Abstract Background Cervical lymph node metastasis (LNM) is an important prognostic factor for patients with non-small cell lung cancer (NSCLC). We aimed to develop and validate machine learning models that use ultrasound radiomic and descriptive semantic features to diagnose cervical LNM in patients with NSCLC. Methods This study included NSCLC patients who underwent neck ultrasound examination followed by cervical lymph node (LN) biopsy between January 2019 and January 2022 from three institutes. Radiomic features were extracted from the ultrasound images at the maximum cross-sectional areas of cervical LNs. Logistic regression (LR) and random forest (RF) models were developed. Model performance was assessed by the area under the curve (AUC) and accuracy, validated internally and externally by fivefold cross-validation and hold-out method, respectively. Results In total, 313 patients with a median age of 64 years were included, and 276 (88.18%) had cervical LNM. Three descriptive semantic features, including long diameter, shape, and corticomedullary boundary, were selected by multivariate analysis. Out of the 474 identified radiomic features, 9 were determined to fit the LR model, while 15 fit the RF model. The average AUCs of the semantic and radiomics models were 0.876 (range: 0.781–0.961) and 0.883 (range: 0.798–0.966), respectively. However, the average AUC was higher for the semantic-radiomics combined LR model (0.901; range: 0.862–0.927). When the RF algorithm was applied, the average AUCs of the radiomics and semantic-radiomics combined models were improved to 0.908 (range: 0.837–0.966) and 0.922 (range: 0.872–0.982), respectively. The models tested by the hold-out method had similar results, with the semantic-radiomics combined RF model achieving the highest AUC value of 0.901 (95% CI, 0.886–0.968). Conclusions The ultrasound radiomic models showed potential for accurately diagnosing cervical LNM in patients with NSCLC when integrated with descriptive semantic features. The RF model outperformed the conventional LR model in diagnosing cervical LNM in NSCLC patients.

Abstract Background Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. Methods In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. Results Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. Conclusion Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Abstract Background Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression. Case presentation H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient’s anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient’s body temperature gradually returned to the normal range and her mood improved significantly. Conclusion Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range.

Abstract Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.

Abstract Background Shenma Jingfu Granule, a traditional Chinese medicine formula, has been used clinically for the treatment of cerebral circulation insufficiency. However, the mechanism involved in alleviating cerebral ischemia has not yet been fully elucidated. Methods An integrated approach involving network pharmacology and transcriptomics was utilized to clarify the potential mechanisms of SMJF Granule. Molecular docking and surface plasmon resonance (SPR) were employed to identify potential targets and ingredients of SMJF Granule. The anti-CI effect of SMJF Granule was determined on the middle cerebral artery occlusion (MCAO) model by using hematoxylin–eosin (H&E) and Nisslʼs staining, as well as triphenyl tetrazolium chloride (TTC) staining, and the potential targets involved in the mechanisms were validated by RT-qPCR and western blotting. Results Integrated analysis revealed the mechanism of SMJF Granule intervening in CI injury might be related to the HIF-1 signaling pathway and angiogenesis. Molecular docking and SPR assays demonstrated robust binding interactions between key compounds like salvianolic acid A and naringenin with the core target HIF-1α protein. The experiment confirmed that SMJF Granule lowered neurological scores, diminished infarct volume, and alleviated histopathological changes in vivo. The possible mechanism of SMJF Granule was due to regulating HIF-1 pathway, which contributed to up-regulating expression of VEGF and vWF in the penumbral region, showing a significant promotion of angiogenesis. Conclusion SMJF Granule promoted angiogenesis through HIF-1α pathway, thereby alleviating cerebral ischemia injury. In addition, our findings provide some evidence that SMJF Granule is a candidate compound for further investigation in treating CI in the clinical. Graphical Abstract

Abstract Stromal fibroblasts are a major stem cell niche component essential for organ formation and cancer development. Fibroblast heterogeneity, as revealed by recent advances in single-cell techniques, has raised important questions about the origin, differentiation, and function of fibroblast subtypes. In this study, we show in mammary stromal fibroblasts that loss of the receptor tyrosine kinase (RTK) negative feedback regulators encoded by Spry1, Spry2, and Spry4 causes upregulation of signaling in multiple RTK pathways and increased extracellular matrix remodeling, resulting in accelerated epithelial branching. Single-cell transcriptomic analysis demonstrated that increased production of FGF10 due to Sprouty (Spry) loss results from expansion of a functionally distinct subgroup of fibroblasts with the most potent branching-promoting ability. Compared to their three independent lineage precursors, fibroblasts in this subgroup are “activated,” as they are located immediately adjacent to the epithelium that is actively undergoing branching and invasion. Spry genes are downregulated, and activated fibroblasts are expanded, in all three of the major human breast cancer subtypes. Together, our data highlight the regulation of a functional subtype of mammary fibroblasts by Spry genes and their essential role in epithelial morphogenesis and cancer development.