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The article presents a study which explored associations between family characteristics and caries experience in 5-year-old children. The study involved data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health and the Public Dental Services in which questionnaires were completed by mothers during pregnancy and when the children were 3 and 5 years of age. Results revealed that caries in 5-year olds were low at 89%.

Abstract: The overall risk associated with exposure to a chemical is determined by combining quantitative estimates of exposure to the chemical with their known health effects. For chemicals that cause carcinogenicity, oral slope factors (OSFs) and inhalation unit risks are used to quantitatively estimate the carcinogenic potency or the risk associated with exposure to the chemical by oral or inhalation route, respectively. Frequently, there is a lack of animal or human studies in the literature to determine OSFs. This study aims to circumvent this problem by developing quantitative structure–activity relationship (QSAR) models to predict the OSFs of chemicals. The OSFs of 70 chemicals based on male/female human, rat, and mouse bioassay data were obtained from the United States Environmental Protection Agency’s Integrated Risk Information System (IRIS) database. A global QSAR model that considered all 70 chemicals as well as species and/or sex-specific QSARs were developed in this study. Study results indicate that the species and sex-specific QSARs (r 2 >0.8, q 2 >0.7) had a better predictive abilities than the global QSAR developed using data from all species and sexes (r 2 =0.77, q 2 =0.73). The QSARs developed in this study were externally validated, and demonstrated reasonable predictive abilities. [Copyright &y& Elsevier]

The article presents a study which examines the impact of electronic health records (EHR) to the physician's behavior, physician-patient interactions, and responses of patients during EHR implementation. The study uses the triangulation design and visual analog scales (VAS) on the analysis. The results show that patient trust in the physician and the security of the therapeutic relationship showed to override most patients' concerns while physicians and medical staff improved work efficiencies.

Background: The interactions of fig wasps and their host figs provide a model for investigating co-evolution. Fig wasps have specialized morphological characters and lifestyles thought to be adaptations to living in the fig's syconium. Although these aspects of natural history are well documented, the genetic mechanism(s) underlying these changes remain(s) unknown. Fig wasp olfaction is the key to host-specificity. The Or83b gene class, an unusual member of olfactory receptor family, plays a critical role in enabling the function of conventional olfactory receptors. Four Or83b orthologous genes from one pollinator (PFW) (Ceratosolen solmsi) and three non-pollinator fig wasps (NPFWs) (Apocrypta bakeri, Philotrypesis pilosa and Philotrypesis sp.) associated with one species of fig (Ficus hispida) can be used to better understand the molecular mechanism underlying the fig wasp's adaptation to its host. We made a comparison of spatial tissue-specific expression patterns and substitution rates of one orthologous gene in these fig wasps and sought evidence for selection pressures. Results: A newly identified Or83b orthologous gene was named Or2. Expressions of Or2 were restricted to the heads of all wingless male fig wasps, which usually live in the dark cavity of a fig throughout their life cycle. However, expressions were widely detected in the antennae, legs and abdomens of all female fig wasps that fly from one fig to another for oviposition, and secondarily pollination. Weak expression was also observed in the thorax of PFWs. Compared with NPFWs, the Or2 gene in C. solmsi had an elevated rate of substitutions and lower codon usage. Analyses using Tajima's D, Fu and Li's D* and F* tests indicated a non-neutral pattern of nucleotide variation in all fig wasps. Unlike in NPFWs, this non-neutral pattern was also observed for synonymous sites of Or2 within PFWs. Conclusion: The sex- and species-specific expression patterns of Or2 genes detected beyond the known primary olfactory tissues indicates the location of cryptic olfactory inputs. The specialized ecological niche of these wasps explains the unique habits and adaptive evolution of Or2 genes. The Or2 gene in C. solmsi is evolving very rapidly. Negative deviation from the neutral model of evolution reflects possible selection pressures acting on Or2 sequences of fig wasp, particularly on PFWs who are more host-specific to figs. [ABSTRACT FROM AUTHOR]

The reconfigurable manufacturing system (RMS) is a new manufacturing technology and paradigm that resolves the contradictions regarding high efficiency, low cost and flexible production in the mass production of part families. Reconfigurable machine tools (RMTs) are the core components of RMSs. A new approach is proposed for the design of RMTs, which is closely related to the process planning of a given box-type part family. The concepts of the processing unit and the processing segment are presented; they are not only the basic elements of the processing plans of machined parts, but also closely related to the structural design of RMTs. Processing units created by processing features can be combined into various processing segments. All the processing units of one processing segment correspond to the machining operations performed by one RMT. By arranging the processing segments according to the processing sequence, a variety of feasible processing plans for a part can be obtained. Through analysis of the established similarity calculation model for processing plans, the most similar processing plans for the parts in a given part family can be determined and used for the structural design of RMTs. Therefore, the designed RMTs can achieve rapid conversion of processing functions with the least module replacement or adjustment to realize the production of the parts in the part family. Taking the production of a gearbox part family as an example, the validity of the presented method is verified. [ABSTRACT FROM AUTHOR]

Offshore floating wind turbines may undergo swaying motions, resulting in significant changes in the wake wind field characteristics of the wind turbine, which can seriously affect the applicability and accuracy of existing wake models. This paper systematically investigates the turbulent wake flows of floating wind turbine with swaying motion based on an improved actuator disk method (ADM). The improved ADM is introduced to reproduce the wake flows of wind turbines, and the characteristics of the turbulent wind fields (i.e., mean wind velocity, turbulence intensity and Reynolds stress) are verified by wind tunnel tests. Furthermore, the wind fields of a floating wind turbine with different swaying amplitudes under turbulent atmospheric boundary layer are simulated, and the mean wind fields and turbulent statistics are analyzed. The performance of various existing wake models (i.e., Jensen model, modified Jensen model and Gaussian model) are compared, and a Gaussian-Shear wake model is proposed for floating wind turbines, which can account for non-uniform inflow and accommodate different swaying amplitudes. The results indicate that the proposed Gaussian-Shear wake model outperforms the other three models in describing the wake flows of floating wind turbines with swaying motions, which can be used for layout optimization and yaw control of offshore floating wind turbines. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is one of the most malignant and lethal digestive-related tumors worldwide. However, acquired drug resistance is a major obstacle concerning anticancer chemotherapy. An increasing number of studies have reported that microRNAs (miRNAs/miRs) are implicated in regulating the sensitivity of drug resistance in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the role of miR-106b-3p in the sensitivity of cisplatin for ESCC. Initially, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to analyze miR-106b-3p and protein-glutamine γ-glutamyltransferase E (TGM3) expression levels in ESCC and non-tumor adjacent tissues. By using bioinformatics software TargetScan, TGM3 was predicted to be a potential downstream target of miR-106-3p. Following verification that TGM3 was a downstream target of miR-106b-3p by the dual-luciferase reporter assay, the effects of miR-106b-3p transfection on KYSE30 cell viability and apoptosis following treatment with cisplatin were confirmed using Cell Counting Kit-8 and flow cytometry assays, respectively. The results revealed that miR-106b-3p levels were upregulated, whereas TMG3 levels were downregulated in ESCC tissues. Dual-luciferase reporter assays confirmed that miR-106b-3p negatively regulated TGM3 expression by binding to its 3′UTR sequence. It was also shown that inhibition of miR-106b-3p could enhance the anti-proliferative effects, while promoting the apoptotic effects of cisplatin in the KYSE30 cell line by targeting TGM3. In conclusion, the present study demonstrated that downregulation of miR-106b-3p may increase the sensitivity of KYSE30 cell to cisplatin by targeting TGM3. [ABSTRACT FROM AUTHOR]

Denmark, Iceland, Norway, and Sweden have all had a similar decline in dental caries during the last 20 years, although the decline has come later in Iceland. The purpose of this study was to compare the caries-preventive methods used for children and adolescents in these four countries. Questionnaires were sent to random samples of dentists, dental hygienists, and dental nurses working with children during 1995 and 1996. The results showed that the use of preventive methods was generally consistent between the countries. Nevertheless there were differences between the countries concerning the choice of preventive strategy for risk patients and also in how prevention was implemented. Danish dental care providers chose oral hygiene education as the priority, which they put into practice. Apart from fluoride varnish for some patients, most of them did not use or recommend fluoride except fluoride toothpaste The Norwegian and Icelandic dental care providers chose both oral hygiene education and the use of fluoride as priorities, while most Swedish dental care providers preferred to provide dietary advice and oral hygiene education, and additional fluoride for risk patients. The differences could not be explained by other variables than nationality, implying that there are differences between the dental cultures in the four countries. The informational basis of decisions on preventive strategies varied between the different dental professionals in each country as well as between the countries, indicating that national professional cultures are being shaped differently. Despite the differences in choice of preventive methods, the dental health of children varies little across the frontiers. This raises the question of the significance of the choice of preventive methods to the decline of dental caries and points towards an urgent need to develop evidence-based preventive strategies. [ABSTRACT FROM AUTHOR]

In our study, we employed an interdisciplinary approach to study the diverse parts of the Missale Nidrosiense, published in 1519. Our aim was a thorough investigation of the materials used and the manufacturing methods that may give indications on dating and provenance of the components of the book and where the book was bound. Initially, visual and multispectral methods were employed to investigate the books' components, printing technology and bookbinding structure. Subsequently, other methods were applied: the composition of metallic components was determined by X-ray fluorescence spectroscopy (XRF). Pigments, printing inks and binders were characterised by using a combination of XRF and synchrotron-based infrared microscopy. Non-invasive dendrochronology based on X-ray tomography was utilised, to indicate date and provenance of the wooden boards of the book. Additionally, we used a biocodicological approach to identify the species of animal used in the parchment. This resulted in a complete biography of the book. We were able to acquire new information about the materials used and their provenance. This provides new information about craft, economy, trade and commercial exchange in the beginning of the sixteenth century in North-west Scandinavia, despite the lack of written documentation from this period. [ABSTRACT FROM AUTHOR]

Polychlorinated dibenzo-para-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) (collectively PCDD/Fs) are toxic and persistent contaminants produced as unintentional by-products of anthropogenic activities. Human exposure to PCDD/Fs occurs primarily through consumption of contaminated food, though point-source soil contamination can also meaningfully contribute to exposure. Environmental soil quality guidelines (ESQGs) for PCDD/Fs have been developed worldwide. In Canada, the 2002 federal ESQG of 4 ng/kg has been adopted by most provinces and is based on limited background soil data. In the remaining provinces, ESQGs derived to be protective of human health range from 15 ng/kg to 95 ng/kg. Internationally, 70% of human health protective ESQGs adopted since 2010 range from 20 ng/kg to 120 ng/kg. Considering the consistency in human health protective ESQGs observed worldwide, the ongoing inputs of PCDD/Fs to the environment and the evolving scientific understanding of PCDD/F toxicity over the last two decades, the federal ESQG appears outdated. As ESQGs are of specific importance in the management of contaminated sites, they must remain protective of human health without being unreasonably cautious. Federal agency review and update of the ESQG for PCDD/Fs appears warranted and should consider the establishment of a risk-based guideline protective of human health. [ABSTRACT FROM AUTHOR]

An important component contributing to the onset of epilepsy is the death of hippocampal neurons. Several studies have shown that Dravet syndrome model mice: Scn1a KO mice have a high number of apoptotic neurons following seizures, but the precise mechanism underlying this remains unclear. The aim of this research was to elucidate the potential molecular mechanism of neuronal apoptosis in Scn1a KO mice by integrating proteomics and transcriptomics, with the ultimate goal of offering better neuroprotection. We found that apoptotic processes were enriched in both proteomic and transcriptomic GO analyses, and KEGG results also indicated that differential proteins and genes play a role in neurotransmission, the cell cycle, apoptosis, and neuroinflammation. Then, we examined the upstream and downstream KGML interactions of the pathways to determine the relationship between the two omics, and we found that the HIF-1 signaling pathway plays a significant role in the onset and apoptosis of epilepsy. Meanwhile, the expression of the apoptosis-related protein VHL decreased in this pathway, and the expression of p21 was upregulated. Therefore, this study suggests that VHL/HIF-1α/p21 might be involved in the apoptosis of hippocampal neurons in Scn1a KO mice. [ABSTRACT FROM AUTHOR]

Simple Summary: Porcine circovirus (PCV2 and PCV3) currently stands as the primary viral agent afflicting intensive pig farming, inflicting substantial economic losses on farms. This study endeavored to explore the prevalence and genetic diversity of PCVs that have circulated in Guangdong province in recent years, a prominent hub for pig production within China. In the current investigation, the prevalence of PCV2, PCV3, and PCV2/3 co-infection was found to be 56.48%, 8.81%, and 8.81%, respectively. Nonetheless, no evidence of PCV4 presence materialized in the course of this study. Moreover, the co-occurrence of PCV2 with classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), pseudo-rabies virus (PRV), and porcine epidemic diarrhea virus (PEDV) emerged as a common phenomenon, with the co-infection rate with PEDV (23.85%) surpassing that of PRV (9.17%), PRRSV (18.35%), or CSFV (0.92%). Subsequently, a detailed analysis of the Cap protein sequence of the PCV2 and PCV3 isolates unveiled several high-frequency mutation sites within the epitope regions. Collectively, this study imparts valuable insights into the prevalence and evolution of PCV2 and PCV3 in China between 2017 and 2023, thereby contributing to the formulation of efficacious prevention and control strategies. Porcine circovirus disease poses a significant threat to the pig farming industry. Globally, four genotypes of porcine circovirus are circulating, with porcine circovirus type 2 and 3 (PCV2 and PCV3) being most strongly associated with clinical manifestations. The recently discovered porcine circovirus type 4 (PCV4) exhibits clinical symptoms resembling porcine dermatitis nephropathy syndrome. This study aimed to assess the prevalence and genetic characteristics of PCVs in Guangdong province, China. A comprehensive analysis was conducted on 193 samples collected from 83 distinct pig farms during the period of 2017–2023. A conventional PCR was employed to investigate the presence of PCV2, PCV3, and PCV4. Among the samples, 56.48%, 8.81%, and 8.81% tested positive for PCV2, PCV3, and PCV2/3 co-infection, respectively. Interestingly, PCV4 was not detected. Whole-genome sequencing was performed on 80 PCV2 isolates and 7 PCV3 isolates. A phylo-genetic analysis revealed that 12 strains belonged to PCV2a, 8 strains belonged to PCV2b, and 60 strains belonged to PCV2d, indicating the prevailing presence of PCV2d in Guangdong province, China. Furthermore, two PCV3 isolates were classified as PCV3a and five strains as PCV3b. Notably, an in-depth analysis of the Cap protein sequence of the PCV2 and PCV3 isolates identified high-frequency mutation sites located in predicted epitope regions. Overall, this study provides valuable insights into the prevalence and evolution of PCV2 and PCV3 during the period of 2017–2023 in Guangdong province, China, thereby contributing to the development of effective prevention and control measures. [ABSTRACT FROM AUTHOR]

• A series of novel alepterolic acid derivatives incorporated with phenylalkylamino moiety were designed, synthesized and charaterized. • Active compounds against MCF-7 cells with IC 50 values less than 10 µM were obtianed. • N -(o -bromo)phenylethylamino alepterolamide (4r) displays the best antiproliferative activity in HepG2 cells. • In silico ADMET analysis suggests compound 4r is unlikely to toxic to normal organs. • Molecular docking study indicates that compound 4r could directly bind to the phosphorylation pocket of HSP27. Aleuritopteris argentea (S. G. Gmél.) Fée is a medicinal fern, the main metabolite of which is an ent - labdane diterpene, i.e. , alepterolic acid. Previous studies showed that this compound featured various biological activities and that the derivatives obtained by introducing an amino moiety on alepterolic acid exhibited better anticancer activity. In order to seek potent anticancer drug candidates, a series of novel alepterolic acid derivatives incorporated with phenylalkylamino moiety were designed, synthesized, and the antiproliferative activity of the obtained compounds against human cancer cell lines (A549, MCF-7, HepG2) was evaluated via MTT assay. The results show that some compounds are active on MCF-7 cells with IC 50 values less than 10 µM, and the activity is better than both that of alepterolic acid and the positive control cisplatin. N -(o -bromo)phenylethylamino alepterolamide (4r) displays the best antiproliferative activity in HepG2 cells, with an IC 50 value of 1.92 ± 0.22 µM. Further mechanistic study reveals that 4r inhibited colony formation and metastasis and induced apoptosis in HepG2 cells via inhibition of Akt. In silico ADMET analysis suggests compound 4r is unlikely to toxic to normal organs. Molecular docking study indicates that compound 4r could directly bind to the phosphorylation pocket of HSP27 to inhibit its phosphorylation. These results implyes that this series of novel alepterolic acid derivatives is worthy to be further explored to seek novel drug candidates for the treatment of cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] • Onychiol B inhibits the production and secretion of pro-inflammatory cytokines. • Onychiol B prevents the production of ROS and reduced the loss of mitochondrial membrane potential in LPS-stimulated RAW264.7 cells. • Onychiol B alleviates pulmonary edema, reverses inflammatory mediator TNF-α, IL-6, and IL-β secretion in lung. Acute lung injury (ALI) is a devastating respiratory disorder characterized by rapid alveolar injury, uncontrolled inflammatory response, etc. Onychiol B is a cyathane diterpene originally isolated from fern plants. In this study, onychiol B can inhibit the production and secretion of pro-inflammatory cytokines such as NO, iNOS , IL-6 and TNF-α in LPS-stimulated RAW264.7 cells by restraining the NF-κB and the p38 MAPK pathway. In addition, it prevents the production of ROS and reduces the loss of mitochondrial membrane potential in LPS-stimulated RAW264.7 cells. Furthermore, in the acute lung injury mouse model induced by LPS injected into the trachea, onychiol B alleviates pulmonary edema, reverses inflammatory mediator TNF-α , IL-6 , and IL-β secretion in lung. In general, our data show that significant anti-ALI effects of onychiol B would render it a potential candidate for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Research on GP5 protein is of great significance in the diagnosis, prevention, and control of porcine reproductive and respiratory syndrome virus (PRRSV). We summarize its genetic variation, immunity, replication, apoptosis, virulence, interaction with viral protein and host proteins, which provides a theoretical foundation for exploring the PRRSV replication mechanisms and developing new vaccines. Porcine reproductive and respiratory syndrome (PRRS) is an acute, febrile, and highly contagious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). Glycoprotein 5 (GP5) is a glycosylated envelope protein encoded by the PRRSV ORF5, which has good immunogenicity and can induce the body to produce neutralizing antibodies. Therefore, study of GP5 protein is of great significance in the diagnosis, prevention, and control of PRRSV and the development of new vaccines. We reviewed GP5 protein genetic variation, immune function, interaction with viral protein and host proteins, induction of cell apoptosis, and stimulation of neutralizing antibodies. GP5 protein's influence on virus replication and virulence, as well as its use as a target for viral detection and immunization are reviewed. [ABSTRACT FROM AUTHOR]

Simple Summary: PRRSV–host protein interactions are of great significance in finding new antiviral targets. We summarize the effects of all the PRRSV structural and nonstructural protein interactions with host proteins and on the protein interactions of the virus itself. These results provide a theoretical foundation for the therapeutic targeting of the intrinsic immune factors of the host protein and exploring viral replication mechanisms. Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), which has been regarded as a persistent challenge for the pig industry in many countries. PRRSV is internalized into host cells by the interaction between PRRSV proteins and cellular receptors. When the virus invades the cells, the host antiviral immune system is quickly activated to suppress the replication of the viruses. To retain fitness and host adaptation, various viruses have evolved multiple elegant strategies to manipulate the host machine and circumvent against the host antiviral responses. Therefore, identification of virus–host interactions is critical for understanding the host defense against viral infections and the pathogenesis of the viral infectious diseases. Most viruses, including PRRSV, interact with host proteins during infection. On the one hand, such interaction promotes the virus from escaping the host immune system to complete its replication. On the other hand, the interactions regulate the host cell immune response to inhibit viral infections. As common antiviral drugs become increasingly inefficient under the pressure of viral selectivity, therapeutic agents targeting the intrinsic immune factors of the host protein are more promising because the host protein has a lower probability of mutation under drug-mediated selective pressure. This review elaborates on the virus–host interactions during PRRSV infection to summarize the pathogenic mechanisms of PRRSV, and we hope this can provide insights for designing effective vaccines or drugs to prevent and control the spread of PRRS. [ABSTRACT FROM AUTHOR]

Aims: Autophagy and exosome secretion in photoreceptor and RPE cells play an important role during diabetic retinopathy (DR). Thioredoxin (Trx) upregulation delays diabetes-induced photoreceptor cell degeneration, which the effect of autophagy and exosome secretion on it is unclear. Therefore, we investigated the effect of them on Trx upregulation to delay diabetes-induced photoreceptor cell degeneration and to identify the potential therapy for DR in the future.Methods: Trx-transgenic mice and 661w cell were as models. Retinal function and morphology were evaluated by electroretinography and H&E staining. TUNEL staining was used to evaluate apoptosis. The protein expression was detected by Western blotting. TEM and mRFP-GFP-LC3 method were used to analyze autophagy.Results: In vitro and in vivo, Trx upregulation can delay diabetes-induced photoreceptor cell degeneration. Moreover, the expression of LC3 and p62 was decreasing and the expression of Alix and CD63 was increasing after Trx overexpression. However, it was inhibited after AMPK inhibitor treatment. Additionally, secreted exosomes from photoreceptor were phagocytosed by RPE cells to regulate its physiological function.Conclusions: Trx upregulation can delay diabetes-induced photoreceptor cell degeneration via AMPK-mediated autophagy and exosome secretion. Secreted exosomes from photoreceptor cells could be phagocytosed and degraded by RPE cells in DR. [ABSTRACT FROM AUTHOR]

Ipatasertib is a selective AKT kinase inhibitor currently in development for the treatment of several solid tumors, including breast and prostate cancers. This study was undertaken to characterize pharmacokinetic profiles of ipatasertib and its metabolite M1 (G‐037720) and to understand the sources of variability. Population pharmacokinetic models of ipatasertib and M1 were developed separately using data from 342 individuals with cancer from 5 phase 1 and 2 studies. The final population pharmacokinetic models for ipatasertib and M1 were 3‐compartmental, with first‐order elimination and sequential zero‐ and first‐order absorption. Ipatasertib bioavailability and M1 formation increased after multiple dosing, resulting in an increase in exposure beyond that expected from accumulation alone. Covariate effects of ipatasertib include decreased oral clearance with increasing age and with coadministration of abiraterone, as well as decreased bioavailability with increasing weight. For ages 37 and 80 years, steady‐state area under the curve (AUCss) was predicted to be 81% and 109%, respectively, of the typical population value (64 years). For body weight of 49 and 111 kg, AUCss was predicted to be 132% and 78%, respectively, of the typical population value (75 kg). The small magnitude of change in ipatasertib exposure is not likely to be clinically relevant. For M1, the peripheral distribution volume and intercompartmental clearance increased with increasing weight. Coadministration of abiraterone was estimated to increase M1 exposure by 61% at steady state. Mild and moderate renal impairment, mild hepatic impairment, and race were not identified as significant covariates in the final models for ipatasertib and M1. [ABSTRACT FROM AUTHOR]

Background: Endotracheal suctioning is one of the most frequently performed invasive procedures by intensive care nurses. Nurses should have adequate knowledge and skills to perform endotracheal suctioning based on the best evidence. Little is known about intensive care nurses' knowledge and practice of evidence-based endotracheal suctioning in Chinese hospitals. The purpose of this study was to investigate intensive care nurses' knowledge and practice of evidence-based recommendations regarding endotracheal suctioning. Specifically, the study aimed to examine (1) intensive care nurses' awareness of and adherence to endotracheal suctioning guidelines and (2) factors influencing their level of awareness and adherence. Methods: A cross-sectional survey of 310 staff nurses working in intensive care units was carried out at Changsha, China. Data on participants' characteristics, awareness of, and adherence to the endotracheal suctioning guidelines were collected through online questionnaires. Following univariate descriptive statistics, the Mann–Whitney U test and Kruskal–Wallis H test were performed using Software Package Statistical Analysis Version 23.0. Results: A total of 281 nurses completed and returned the survey (response rate = 90.6 %). One-half to three-quarters of the nurses knew 21 of the 26 evidence-based practices and believed their practices followed the guidelines. Over half of them were unaware of the difference between open and close suctions and the pros and cons of using hyperinflation. Almost 50 % of nurses believed some of their clinical practices did not follow the evidence-based recommendations, such as not routinely using normal saline and using 80–120 mmHg suction pressure during endotracheal suctioning. Nurses with endotracheal suctioning training demonstrated significantly higher awareness of endotracheal suctioning recommendations and higher adherence levels than untrained nurses. Conclusions: The study findings revealed that Chinese intensive care nurses lacked awareness of several essential evidence-based endotracheal suctioning practices, and there were gaps between their current practice and the guideline recommendations. Further research should emphasize revealing barriers and facilitators of implementing evidence-based endotracheal suctioning practices as well as developing context-suitable interventions for guideline implementation. [ABSTRACT FROM AUTHOR]

The objectives of the study were to use tumor size data from 10 phase II/III atezolizumab studies across five solid tumor types to estimate tumor growth inhibition (TGI) metrics and assess the impact of TGI metrics and baseline prognostic factors on overall survival (OS) for each tumor type. TGI metrics were estimated from biexponential models and posttreatment longitudinal data of 6699 patients. TGI‐OS full models were built using parametric survival regression by including all significant baseline covariates from the Cox univariate analysis followed by a backward elimination step. The model performance was evaluated for each trial by 1000 simulations of the OS distributions and hazard ratios (HR) of the atezolizumab‐containing arms versus the respective controls. The tumor growth rate estimate was the most significant predictor of OS across all tumor types. Several baseline prognostic factors, such as inflammatory status (C‐reactive protein, albumin, and/or neutrophil‐to‐lymphocyte ratio), tumor burden (sum of longest diameters, number of metastatic sites, and/or presence of liver metastases), Eastern Cooperative Oncology Group performance status, and lactate dehydrogenase were also highly significant across multiple studies in the final multivariate models. TGI‐OS models adequately described the OS distribution. The model‐predicted HRs indicated good model performance across the 10 studies, with observed HRs within the 95% prediction intervals for all study arms versus controls. Multivariate TGI‐OS models developed for different solid tumor types were able to predict treatment effect with various atezolizumab monotherapy or combination regimens and could be used to support design and analysis of future studies. [ABSTRACT FROM AUTHOR]

[Display omitted] Conjugates of alepterolic acid with 5-fluorouracil derivatives have been synthesized in 70–90% yields. The cytotoxic evaluation against two human cancer cell lines, viz. MCF-7 (breast) and A549 (lung), using MTT assay showed anticancer activities of the obtained compounds. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a serious neurodegenerative disease that is induced by hyperglycaemia. Oxidative stress, inflammation and endoplasmic reticulum (ER) stress are involved in the development of DR. Sulforaphane (SF) is widely found in cruciferous plants and has a protective effect against retinal neurodegeneration in diabetes, but the mechanism is unclear. In this study, we investigated the mechanism by which SF protects against photoreceptor degeneration in diabetes. In vivo, a mouse model of diabetes was established by streptozotocin (STZ) injection, and the mice were treated with/without SF. Electroretinography (ERG) and H&E staining were used to evaluate retinal function and morphology. In vitro, 661w cells were treated with AGEs with/without SF. Cell viability and apoptosis were analysed by CCK-8 assay and flow cytometry. The expression of proteins and genes was assessed by western blot and qRT-PCR. The amplitude of the a-wave was decreased and the morphology was changed in the diabetic mice, and these changes were delayed by SF treatment. The percentage of apoptotic cells was increased and the cell viability was decreased after the treatment of 661w cells with AGEs. Moreover, the expression of GRP78, Txnip and TNFα was increased, however, this increased expression was reversed by SF treatment via AMPK pathway activation. Taken together, these data show that SF can delay photoreceptor degeneration in diabetes, and the underlying mechanism is related to the inhibition of ER stress, inflammation and Txnip expression through the activation of the AMPK pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] Ancepsone A, a new sesterterpene with 13,19-epoxycheilanthane skeleton, i.e (17 Z)-13,19-epoxycheilanth-1,17-diene-2-ol-3-one (1), together with eight known natural products (2 ∼ 9) were isolated from Aleuritopteris anceps. The structure of the new compound was established by means of 1D and 2D NMR, MS, and single-crystal X-ray diffraction methods. All compounds were isolated from A. anceps for the first time. Ancepsone A and the isolated flavonoids can moderately inhibit the proliferation of cancer cells. [ABSTRACT FROM AUTHOR]

In order to compare between in vivo toxicity studies, dosimetry is needed to translate study-specific dose regimens into dose metrics such as tissue concentration. These tissue concentrations may then be compared with in vitro bioactivity assays to perhaps identify mechanisms relevant to the lowest observed effect level (LOEL) dose group and the onset of the observed in vivo toxicity. Here, we examine the perfluorinated compounds (PFCs) perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS). We analyzed 9 in vivo toxicity studies for PFOA and 13 in vivo toxicity studies for PFOS. Both PFCs caused multiple effects in various test species, strains, and genders. We used a Bayesian pharmacokinetic (PK) modeling framework to incorporate data from 6 PFOA PK studies and 2 PFOS PK studies (conducted in 3 species) to predict dose metrics for the in vivo LOELs and no observed effect levels (NOELs). We estimated PK parameters for 11 combinations of chemical, species, strain, and gender. Despite divergent study designs and species-specific PK, for a given effect, we found that the predicted dose metrics corresponding to the LOELs (and NOELs where available) occur at similar concentrations. In vitro assay results for PFOA and PFOS from EPA’s ToxCast project were then examined. We found that most in vitro bioactivity occurs at concentrations lower than the predicted concentrations for the in vivo LOELs and higher than the predicted concentrations for the in vivo NOELs (where available), for a variety of nonimmunological effects. These results indicate that given sufficient PK data, the in vivo LOELs dose regimens, but not necessarily the effects, could have been predicted from in vitro studies for these 2 PFCs. [ABSTRACT FROM PUBLISHER]

Citrus fruits exhibit vivid color and are favored extensively. However, the biochemical and molecular mechanism of Citrus Reticulata Blanco fruits coloring, especially the effect of transplantation on fruits coloring, is unclear. Herein, RNA-Seq and carotenoids profiling were applied to investigate the effect of transplantation on Orah mandarin fruits coloring. Transplantation induces fruit color shallowing, Ca2+ and ACC level declining and IAA level increasing. Transplantation induced variation in fruit skin and pulp carotenoids, mainly β-citraurin as one of the important pigments of citrus peel. 2253 up-regulated genes, 1103 down-regulated genes in skin and 815 up-regulated genes, 534 down-regulated genes in pulp of transplanted tree fruits were identified by RNA-Seq. The DEGs involved hormone signal, carotenoids biosynthesis and TFs such as MYB and bHLH family TFs. The carotenoid cleavage dioxygenase gene (Ciclev10028113m.g) is positively correlated with β-citraurin and regulated directly and/or indirectly by MYB1R1, PIF4, ACC and IAA. Integrative analyses revealed potential molecular insights into Orah mandarin peel color variation during transplantation. • Transplantation resulted in fruit color shallowing and decreased fruit Ca2+ level. • Transplantation induced variation in vast carotenoids in Orah mandarin fruit skin and pulp, especially for β-citraurin as one of the important pigments of citrus peel. • Transplantation induced variation in a large number of DEGs, involving metabolic processes of hormone signal, carotenoid biosynthesis and transcription factors as MYB and bHLH family TFs. • Integrative analyses revealed potential molecular insights into fruit skin color variation during Orah mandarin transplant. [ABSTRACT FROM AUTHOR]

Investigates the mechanism of wave break generation during ventricular fibrillation. Production of wave through head-tail interaction between waves and filament break.

Introduction: Cancer-related fatigue is common in patients with advanced lung cancer. It not only interferes with patients' health-related quality of life, but also increases the caregiving burden of their caregivers. Acceptance and commitment therapy is emerging as a novel way to advocate accepting negative experiences and taking effective actions based on their own values to help patients commit meaningful actions in the course of cancer diseases. This trial aims to test the feasibility, acceptability and preliminary effects of acceptance and commitment therapy for fatigue interference in patients with advanced lung cancer and the caregiver burden., Method and Analysis: A two-arm, assessor-blind pilot randomised controlled trial will be conducted. A total of 40 advanced lung cancer patient-caregiver dyads, who live in rural areas, will be recruited from a university-affiliated hospital in central China. The participants will be randomised to receive an online six-session acceptance and commitment therapy (i.e. involving metaphors, experiential exercises and mindfulness exercises facilitated by virtual reality technology) plus health education (intervention group, n=20) or health education (control group, n=20). Outcomes will be measured at baseline and 1 week postintervention. The primary outcomes are study feasibility (i.e. eligibility rate, recruitment rate, attrition rate and adherence rate), fatigue interference and caregiver burden. The secondary outcomes are health-related quality of life, meaning in life, psychological flexibility and mindful attention. Semistructured interviews will be conducted to explore the feasibility and experiences of the intervention in a subsample of 10 participants from the intervention group., Ethics and Dissemination: This study has been approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No. 2023.030) and the Medical Ethics Committee of Xiangya Hospital Central South University (No. 202305336). The findings will be disseminated in peer-reviewed journals and through local or international conference presentations., Trial Registration Number: NCT05885984., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Alepterolic acid is a diterpene occurring in the fern Aleuritopteris argentea with potential biological activity that warrants further structural modification. In the present work, sixteen alepterolic acid derivatives were synthesized and evaluated for their anticancer activities. Among them, N-[m-(trifluoromethoxy)phenyl] alepterolamide displayed comparable activity (IC 50 =4.20±0.21 μM) in MCF-7 cells. Moreover, mechanistic investigations indicated this compound was significantly capable of diminishing cell proliferation and viability of MCF-7 cells. After treatment with N-[m-(trifluoromethoxy)phenyl] alepterolamide, a significant increase in cleaved caspase-9, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP) and Bax/Bcl2 ratio were observed in MCF-7 cells, leading to caspase-dependent apoptotic pathways. Further studies showed this compound promoted cellular apoptosis and inhibited migration in MCF-7 cells via modulation of the Akt/p70 S6K signaling pathway. All these results revealed the potential of N-[m-(trifluoromethoxy)phenyl] alepterolamide as an appealing therapeutic drug candidate for breast cancer., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

The H9N2 avian influenza virus (AIV) represents a significant risk to both the poultry industry and public health. Our surveillance efforts in China have revealed a growing trend of recent H9N2 AIV strains exhibiting a loss of hemagglutination activity at 37°C, posing challenges to detection and monitoring protocols. This study identified a single K141N substitution in the hemagglutinin (HA) glycoprotein as the culprit behind this diminished hemagglutination activity. The study evaluated the evolutionary dynamics of residue HA141 and studied the impact of the N141K substitution on aspects such as virus growth, thermostability, receptor-binding properties, and antigenic properties. Our findings indicate a polymorphism at residue 141, with the N variant becoming increasingly prevalent in recent Chinese H9N2 isolates. Although both wild-type and N141K mutant strains exclusively target α,2-6 sialic acid receptors, the N141K mutation notably impedes the virus's ability to bind to these receptors. Despite the mutation exerting minimal influence on viral titers, antigenicity, and pathogenicity in chicken embryos, it significantly enhances viral thermostability and reduces plaque size on Madin-Darby canine kidney (MDCK) cells. Additionally, the N141K mutation leads to decreased expression levels of HA protein in both MDCK cells and eggs. These findings highlight the critical role of the K141N substitution in altering the hemagglutination characteristics of recent H9N2 AIV strains under elevated temperatures. This emphasizes the need for ongoing surveillance and genetic analysis of circulating H9N2 AIV strains to develop effective control and prevention measures.IMPORTANCEThe H9N2 subtype of avian influenza virus (AIV) is currently the most prevalent low-pathogenicity AIV circulating in domestic poultry globally. Recently, there has been an emerging trend of H9N2 AIV strains acquiring increased affinity for human-type receptors and even losing their ability to bind to avian-type receptors, which raises concerns about their pandemic potential. In China, there has been a growing number of H9N2 AIV strains that have lost their ability to agglutinate chicken red blood cells, leading to false-negative results during surveillance efforts. In this study, we identified a K141N mutation in the HA protein of H9N2 AIV to be responsible for the loss of hemagglutination activity. This finding provides insight into the development of effective surveillance, prevention, and control strategies to mitigate the threat posed by H9N2 AIV to both animal and human health., Competing Interests: The authors declare no conflict of interest.

Triple-negative breast cancer (TNBC) is characterized by strong invasiveness, high relapse rates, and poor overall survival. It occurs in approximately 15-20 % of all breast cancer cases. Natural compounds are a promising option for managing breast cancer. ent-8(14),15-Pimaradiene-2β,19-diol (JXE-23), is a pimaradiene isolated from the fern Aleuritopteris albofusca. However, the effects and molecular mechanisms of JXE-23 on cancer cells are still unknown. Thus, this study was designed to determine the potential of JXE-23 for its anticancer properties in TNBC cells. JXE-23 was evaluated for its antiproliferative activity in vitro against human breast cancer cell lines, and showed selectively cytotoxic activity against MDA-MB-468, an EGFR-overexpressing TNBC cancer cell line, with an IC 50 value of 1.17±0.04 μM. Moreover, mechanistic investigations indicated that JXE-23 was significantly capable of inhibiting cell proliferation and viability in MDA-MB-468 cells. In addition, JXE-23 exerted an anticancer effect against MDA-MB-468 cells via restraining cell migration in a dose-dependent mode. Moreover, after treatment with JXE-23, the protein expressions of pEGFR, pERK, pAkt and p-p70 S6K were significantly reduced in MDA-MB-468 cells. The results underscored that JXE-23 could be a potential lead compound for the treatment of EGFR-overexpressing TNBC cells., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Sodium butyrate (NaB) has garnered attention in recent years for its ability to impede the malignant progression of tumors. In order to explore the potential inhibitory effects of NaB on the replication of Marek's disease virus (MDV) and subsequent lymphoma formation, newly hatched chickens were infected with the vvMDV Md5 strain and administered NaB prior to (prevention group) or following (treatment group) Md5 inoculation. The results revealed that NaB played a pivotal role in diminishing both the incidence and fatality rates in chickens afflicted with Md5 infection. Notably, NaB exhibited a remarkable capacity to inhibit the expression of MDV immediate early genes, i.e., ICP4 and ICP27 , thus attenuating tumorigenesis in the chicken spleen. To further elucidate the mechanism of NaB on lymphoma cells, MDV bearing lymphoma cells, i.e., MSB-1 were exposed to NaB for 24 h prior to various experimental tests. The results revealed that NaB effectively hindered the proliferation, migration, and colony formation of MSB-1 cells. Furthermore, NaB demonstrated the ability to modulate the key molecules in mitochondrial apoptosis pathway. Taken together, these findings reveal that NaB can impede the lymphoma caused by MDV via regulating the mitochondrial apoptosis pathway, both in vitro and in vivo . These results suggest that the utilization of NaB warrants serious consideration as a promising approach for the prevention of MDV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Zhou, Yang, Zheng, Chen, Chang, Cai, Wen, Wang, Chen and Qin.)

Background: This research examines the nuanced challenges confronting Chinese university students within the dynamic milieu of Chinese education. The study comprehensively investigates factors encompassing educational progress, social development, cognitive focus, and Psychological Well-being (PWB), specifically emphasizing the role of sports participation., Methods: To scrutinize the moderation-mediation nexus between cultural context and social development, a distribution of 500 questionnaires was administered to Chinese university students, yielding 413 responses, corresponding to an 82.6% response rate. Methodologically, this study employed moderation and mediation analyses, incorporating statistical techniques such as a principal component matrix, factor analysis, and hierarchical regression., Findings: Prominent findings underscore the significant impact of age on educational progress, shaping the trajectory of academic advancement. Cumulative Grade Point Average (CGPA) emerges as a promising metric, establishing a link between academic performance and educational progress. Active involvement in sports and physical activities (PSPA) positively affects academic performance and study habits. Participation in sports teams and clubs (ISTC) enriches social development by nurturing interpersonal relationships, teamwork, and leadership skills. Sports activities (ESA) correlate with enhanced cognitive focus and improved psychological well-being. Significantly, the findings unveil a nuanced association between Perceived Social Development Through Sports (PSDTS) and educational progress., Conclusions: Cultural Context (CC) moderates PSDTS, Sport-induced Cognitive Focus (SICF), and PWB, influencing educational progress. This study emphasizes the need for enhanced support systems-academic guidance, awareness, sports programs, and cultural competence training-to advance student well-being and academic achievement in China, fostering an empowering educational environment for societal progress., (© 2024. The Author(s).)

Two pairs of new bisabolane-type sesquiterpenoids, (+)-aspersydowin A (7S) [(+)-1], (-)-aspersydowin A (7R) [(-)-1], (+)-aspersydowin B (7S,11S) [(+)-2], (-)-aspersydowin B (7R,11R) [(-)-2], along with six known compounds (1-8) were isolated from the fungus Aspergillus sydowii. Compounds 1 and 2 are enantiomers resolved by the Chiralpak IC, using a hexane- propan-2-ol mobile phase. The structure of 1 and 2 with absolute configuration were assigned tentatively by 1D ( 1 H, 13 C, and DEPT) & 2D (HSQC, 1 H- 1 H COSY, HMBC, and NOESY) NMR data analyses and ECD calculations. Compounds 1-8 were screened for the biological activities in vitro. The results showed that compounds 3, 4 and 8 exhibited immunosuppressive activities with IC 50 values of 10.9, 17.6 and 13.4 μM, respectively., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Gene therapy is a new class of medical treatment that alters part of a patient's genome through the replacement, deletion, or insertion of genetic material. While still in its infancy, gene therapy has demonstrated immense potential to treat and even cure previously intractable diseases. Nevertheless, existing gene therapy prices are high, raising concerns about its affordability for U.S. payers and its availability to patients. We assess the potential financial impact of novel gene therapies by developing and implementing an original simulation model which entails the following steps: identifying the 109 late-stage gene therapy clinical trials underway before January 2020, estimating the prevalence and incidence of their corresponding diseases, applying a model of the increase in quality-adjusted life years for each therapy, and simulating the launch prices and expected spending of all available gene therapies annually. The results of our simulation suggest that annual spending on gene therapies will be approximately $20.4 billion, under conservative assumptions. We decompose the estimated spending by treated age group as a proxy for insurance type, finding that approximately one-half of annual spending will on the use of gene therapies to treat non-Medicare-insured adults and children. We conduct multiple sensitivity analyses regarding our assumptions and model parameters. We conclude by considering the tradeoffs of different payment methods and policies that intend to ensure patient access to the expected benefits of gene therapy., (© 2023. The Author(s).)

Purpose: To explore breastfeeding from 6 to 18 months of age and to study the association between breastfeeding and caries prevalence at 5 years of age., Methods: The study included 1088 children from one Norwegian county and was based on the Norwegian Mother, Father and Child Cohort Study (MoBa). The children had clinical dental examination at 5 years of age, and parents answered a questionnaire, which included information on breastfeeding, oral health behaviour and child characteristic. Multivariate logistic regressions were performed. The study was ethically approved., Results: Of the studied children, 77% were breastfed at 6 months of age and 16% were still breastfed at 18 months of age. Few children (6%) were breastfed during night at 18 months of age, while 11% received sugary drink during night. No association was found between breastfeeding up to 18 months of age and caries prevalence at 5 years of age ( p  > .05). Children who at 18 months of age had their teeth brushed less than twice daily (OR 2.4, CI 1.5-3.9), consumed sugary drink once a week or more often (OR 1.7, CI 1.1-2.7) and had non-Western parents (OR 3.4, CI 1.5-8.1) were more likely to have caries experience at 5 years of age than other children., Conclusion: Breastfeeding up to 18 months of age was not associated with caries development during preschool age.

Objective: Inflammation of the surrounding environment is a major reason causing loss or injury of oligodendrocyte precursor cells (OPCs) in myelin-associated diseases. Lipopolysaccharide-activated microglia can release various inflammatory factors such as tumor necrosis factor-α (TNF-α). One of the ways of OPC death is necroptosis, which can be triggered by TNF-α, a death receptor ligand, by activating receptor-interacting protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling pathway. This study investigated whether inhibiting microglia ferroptosis can decrease TNF-α release to alleviate OPC necroptosis., Methods: Lipopolysaccharide and Fer-1 stimulate BV2 cells. The expressions of GPX4 and TNF-α were detected by western blot and quantitative real-time PCR; malondialdehyde, glutathione, iron, and reactive oxygen species were measured by the assay kits. After lipopolysaccharide stimulation of BV2 cells, the supernatant was taken to culture OPC. The protein expression levels of RIPK1, p-RIPK1, RIPK3, p-RIPK3, MLKL, and p-MLKL were detected by western blot., Results: Lipopolysaccharide administration could induce ferroptosis in microglia by decreasing ferroptosis marker GPX4, while ferroptosis inhibitor Fer-1 could significantly increase GPX4 level. Fer-1 prevented oxidative stress and iron concentration elevation and alleviated mitochondrial damage in lipopolysaccharide-induced BV2 cells. The results revealed that Fer-1 downregulated the release of lipopolysaccharide-induced TNF-α in microglia and attenuated OPC necroptosis by significantly decreasing the expression levels of RIPK1, p-RIPK1, MLKL, p-MLKL, RIPK3, and p-RIPK3., Conclusion: Fer-1 may be a potential agent for inhibiting inflammation and treating myelin-related diseases., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The impact of the professional learning community on teachers' professional development has been studied in different contexts. However, the number of studies on the voices of secondary teachers in Malaysian Independent Chinese Secondary Schools [MICSS) needs to be more detailed. This study aimed to investigate how teachers in MICSS view the impact of the Professional Learning Community (PLC) on their professional development. Data for this study was collected using semi-structured interviews with eight MICSS teachers selected from two different-scale MICSSs. The patterns were analyzed by repetitive data reading, data coding, and theme creation. The findings show that with the help of PLC, MICSS teachers may improve their professional development more effectively, particularly in enhancing their knowledge of their subject, students, effective teaching methodology, and sense of occupational belonging. Moreover, collective learning and classroom observation procedures are the most effective among all the PLC activities in the MICSS context. The findings have practical implications for teachers and trainers to improve teachers' profession by establishing professional learning groups., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Streptomyces pactum (Act12) can both promote plant growth and strengthen heavy metal mobilization. Nevertheless, the mechanisms of how Act12 works during the phytoextraction process are still unknown. The present work investigated whether the metabolites produced by Act12 could influence the seed germination and the growth of potherb mustard and explored its mobilizing effect on soil cadmium (Cd) and zinc (Zn). The results showed that the germination potential and rate of potherb mustard seed treated with Act12 fermentation broth were 1.0- and 0.32-folds higher than those of control, probably due to the interruption of seed dormant stage. We also found that Act12 inoculation not only promoted the dry biomass (6.82%) of potherb mustard, but also increased the leaf chlorophyll (11.8%) and soluble protein (0.35%) production. The boosted seed germination rate under Act12 treatment (up to 63.3%) indicated that Act12 enhanced the resistance of potherb mustard seeds to Cd and Zn and alleviated their physiological toxicity. The generated metabolites during the Act12 fermentation posed positive impact on the availability of soil Cd and Zn. These findings bring new insight into the Act12-assisted phytoextraction of Cd and Zn from contaminated soils., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Citrus reticulata Blanco 'Orah' is grown throughout southern China and provides enormous economic value. However, the agricultural industry has suffered substantial losses during recent years due to marbled fruit disease. The present study focuses on the soil bacterial communities associated with marbled fruit in 'Orah'. The agronomic traits and microbiomes of plants with normal and marbled fruit from three different orchards were compared. No significant differences were found in agronomic traits between the groups, except for higher fruit yields and higher quality of fruits in normal fruit group. Additionally, a total of 2,106,050 16S rRNA gene sequences were generated via the NovoSeq 6000. The alpha diversity index (including the Shannon and Simpson indices), Bray-Curtis similarity, and principal component analyses indicated no significant differences in microbiome diversity between normal and marbled fruit groups. For the healthy 'Orah', the most abundant associated phyla were Bacteroidetes, Firmicutes, and Proteobacteria. In comparison, Burkholderiaceae and Acidobacteria were the most abundant taxa with the marbled fruit group. In addition, the family Xanthomonadaceae and the genus Candidatus Nitrosotalea were prevalent with this group. Analysis using the Kyoto Encyclopedia of Genes and Genomes pathways showed that several pathways related to metabolism significantly differed between the groups. Thus, the present study provides valuable information regarding soil bacterial communities associated with marbled fruit in 'Orah'., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Wang, Liu, Liao, Zeng, Hu, Wei, Tan, Liu, Li, Huang, Chen, Wei and Qin.)

Alepterolic acid is a natural diterpenoid isolated from Aleuritopteris argentea with potential anti-cancer activity. In this study, alepterolic acid was modified to construct a series of arylformyl piperazinyl derivatives (3a-3p). The synthesized derivatives were fully characterized with HRMS, NMR, and IR. Four compounds with inhibition rate higher than 30 % at 10 μM (3f, 3n, 3g and 3k) were further measured to obtain the IC 50 values against four cancer cell lines, including hepatoma cell lines HepG2, lung cancer cell lines A549, estrogen receptor-positive cell lines MCF7, and triple-negative breast cancer (TNBC) cell lines MDA-MB-231 by MTT assay. It was found that these compounds were more effective to HepG2 and MDA-MB-231 cells, while less toxic to A549 and MCF7 cells, and compound 3n as the most toxic derivatve against MDA-MB-231 cell lines, with IC 50 value of 5.55±0.56 μM. Trypan blue staining and colony formation assay showed that compound 3n inhibited the growth of MDA-MB-231 cells and prevented colony formation. Hoechst staining, flow cytometry and western blot analysis revealed that compound 3n induced caspase-dependent apoptosis in MDA-MB-231 cells. Conclusively, compound 3n was demonstrated to be a potential anti-cancer lead compound for further investigation., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

The ultimate purpose of phytoextraction is not only to remove heavy metals from soil but also to improve soil quality. Here, we evaluated how the joint effect of Streptomyces pactum (strain Act12) and inorganic (Hoagland's solution) and organic (humic acid and peat) nutrients affected the phytoextraction practice of cadmium (Cd) and zinc (Zn) by potherb mustard, and the microbial community composition within rhizosphere was also investigated. The results indicated that the nutrients exerted synergistically with Act12, all increasing the plant biomass and Cd/Zn uptakes. The inoculation of Act12 alone significantly increased dehydrogenase activity of rhizosphere soil (P < 0.05), while urease and alkaline phosphatase activities varied in different dosage of Act12. Combined application of microbial strain with nutrients increased enzymatic activities with the elevated dosage of Act12. 16S ribosomal RNA high-throughput sequencing analysis revealed that Act12 inoculation reduced the diversity of rhizosphere bacteria. The Act12 and nutrients did not change dominant phyla i.e., Proteobacteria, Bacteroidetes, Gemmatimonadetes, Actinobacteria and Acidobacteria, but their relative abundance differed among the treatments with: Peat > Act12 > Humic acid > Hoagland's solution. Comparatively, Sphingomonas replaced Thiobacillus as dominant genus after Act12 application. The increase in the Sphingomonas and Flavisolibacter abundances under Act12 and nutrients treatments gave rise to growth-promoting effect on plant. Our results revealed the important role for rhizosphere microbiota in mediating soil biochemical traits and plant growth, and our approach charted a path toward the development of Act12 combined with soil nutrients to enhance soil quality and phytoextraction efficiency in Cd/Zn-contaminated soils., (Copyright © 2022. Published by Elsevier B.V.)

Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell membrane for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, the activity of ACE2 in single living cell is firstly determined using a nanokit coupled electrospray ionization mass spectrometry (nanokit-ESI-MS). Upon the insertion of a micro-capillary into the living hACE2-CHO cell and the electrochemical sorting of the cytosol, the target ACE2 enzyme hydrolyses angiotensin II inside the capillary to generate angiotensin 1-7. After the electrospray of the mixture at the tip of the capillary, the product is differentiated from the substrate in molecular weight to achieve the detection of ACE2 activity in single cells. The further measurement illustrates that the inflammatory state of cells does not lead to the significant change of ACE2 catalytic activity, which elucidates the relationship between intracellular ACE2 activity and inflammation at single cell level. The established strategy will provide a specific analytical method for further studying the role of ACE2 in the process of virus infection, and extend the application of nanokit based single cell analysis., Competing Interests: The authors report no declarations of interest., (© 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.)

Porcine reproductive and respiratory syndrome virus (PRRSV) has continuously mutated since its first isolation in China in 1996, leading to difficulties in infection prevention and control. Infections caused by PRRSV-2 strains are the main epidemic strains in China, as determined by phylogenetic analysis. In this study, we focused on the prevalence and genetic variations of the non-structural protein 4 (NSP4) from PRRSV-2 over the past 20 years in China. The fundamental biological properties of the NSP4 were predicted, and an analysis and comparison of NSP4 homology at the nucleotide and amino acid levels was conducted using 123 PRRSV-2 strains. The predicted molecular weight of the NSP4 protein was determined to be 21.1 kDa, and it was predicted to be a stable hydrophobic protein that lacks a signal peptide. NSP4 from different strains exhibited a high degree of amino acid (85.8-100%) and nucleotide sequence homology (81.0-100%). Multiple amino acid substitutions were identified in NSP4 among 15 representative PRRSV-2 strains. Phylogenetic analysis showed that the lineage 8 and 1 strains, the most prevalent strains in China, were indifferent clades with a long genetic distance. This analysis will help fully elucidate the parameters of the PRRSV NSP4 epidemic in China to lay a foundation for adequate understanding of the function of NSP4. Genetic information results from the accumulation of conserved and non-conserved sequences. The high conservation of the NSP4 gene determines the most basic life traits and functions of PRRSV. Analyzing the spatial structure of NSP4 protein and studying the genetic evolution of NSP4 not only provide the theoretical basis for how NSP4 participates in the regulation of the innate response of the host but also provide a target for genetic manipulation and a reasonable target molecule and structure for new drug molecules., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)