Synergistic antibacterial and anti-biofilm mechanisms of ultrasound combined with citral nanoemulsion against Staphylococcus aureus 29213.

This study investigated the antibacterial and antibiofilm mechanism of ultrasound (US) combined with citral nanoemulsion (CLNE) against Staphylococcus aureus and mature biofilm. Combined treatments resulted in greater reductions in bacterial numbers compared to ultrasound or CLNE treatments alone. Confocal laser scanning microscopy (CLSM), flow cytometry (FCM), protein nucleic acid leakage, and N-phenyl-l-naphthylamine (NPN) uptake analysis showed that the combined treatment disrupted cell membrane integrity and permeability. Reactive oxygen species (ROS) and malondialdehyde (MDA) assays indicated that US+CLNE exacerbated cellular oxidative stress and membrane lipid peroxidation. Field emission scanning electron microscopy (FESEM) revealed that the synergistic processing of ultrasound and CLNE resulted in cell rupture and collapse. In addition, US+CLNE showed a more pronounced removal effect than both alone in the biofilm on the stainless steel sheet. US+CLNE reduced biomass, the number of viable cells in the biofilm, cell viability and EPS polysaccharide contents. The results of CLSM also showed that US+CLNE disrupted the structure of the biofilm. This research elucidates the synergistic antibacterial and anti-biofilm mechanism of ultrasound combined citral nanoemulsion, which provides a safe and efficient sterilization method for the food industry.

iEssLnc: quantitative estimation of lncRNA gene essentialities with meta-path-guided random walks on the lncRNA-protein interaction network.

Gene essentiality is defined as the extent to which a gene is required for the survival and reproductive success of a living system. It can vary between genetic backgrounds and environments. Essential protein coding genes have been well studied. However, the essentiality of non-coding regions is rarely reported. Most regions of human genome do not encode proteins. Determining essentialities of non-coding genes is demanded. We developed iEssLnc models, which can assign essentiality scores to lncRNA genes. As far as we know, this is the first direct quantitative estimation to the essentiality of lncRNA genes. By taking the advantage of graph neural network with meta-path-guided random walks on the lncRNA-protein interaction network, iEssLnc models can perform genome-wide screenings for essential lncRNA genes in a quantitative manner. We carried out validations and whole genome screening in the context of human cancer cell-lines and mouse genome. In comparisons to other methods, which are transferred from protein-coding genes, iEssLnc achieved better performances. Enrichment analysis indicated that iEssLnc essentiality scores clustered essential lncRNA genes with high ranks. With the screening results of iEssLnc models, we estimated the number of essential lncRNA genes in human and mouse. We performed functional analysis to find that essential lncRNA genes interact with microRNAs and cytoskeletal proteins significantly, which may be of interest in experimental life sciences. All datasets and codes of iEssLnc models have been deposited in GitHub (https://github.com/yyZhang14/iEssLnc).

Unintentional injuries among children with developmental disabilities are a public health challenge in China.

Child injury is a significant global health issue that contributes to both morbidity and mortality in children. Children with developmental disabilities are at a high risk for injuries due to a combination of environmental barriers and health conditions. However, little research has assessed the prevalence of injuries among this population in China. Using administrative data from a micro insurance programme for children with developmental disabilities (such as autism, intellectual disability, cerebral palsy and Down syndrome) under the age of 19, we estimated the risk of unintentional injuries reported in insurance claims. Between 2017 and 2020, there were 190 insurance claims (0.53%) reporting nonfatal unintentional injuries and six reporting fatal injuries. The cumulative hazard rate of unintentional injuries by the end of 1 year is 1.21% and is negatively associated with children's age. These findings suggest the need for increased safety support for children with developmental disabilities, particularly in early childhood.

Social and paternal female choice for male MHC genes in golden snub-nosed monkeys (Rhinopithecus roxellana).

Genes of the major histocompatibility complex (MHC) play important roles in vertebrate immunocompetence. MHC genes thus offer females indirect benefits to mate choice through the production of offspring of an optimal MHC genotype. Females may choose males with specific MHC haplotypes, dissimilar MHC genotypes, MHC heterozygous males or MHC-diverse males. We tested these four alternatives for both female social and paternal choice in wild golden snub-nosed monkeys (Rhinopithecus roxellana) by examining overall genetic variability (via microsatellites) and four MHC-genes (DRB1, DRB2, DQA1 and DQB1). Monte Carlo randomization tests showed that MHC dissimilarity was favored for social choice (males to which females were socially affiliated) and intermediate MHC dissimilarity was favored in paternal choice (fathers of offspring). No evidence of inbreeding avoidance was found for either social or paternal mates. We found that MHC heterozygotes, higher microsatellite multi-locus heterozygosity and higher microsatellites diversity were favored for social mates, and higher microsatellite diversity was favored for paternal mates. Independent of male age, we found that the formation of male-female social pairings is significantly predicted by compatibility based on the sharing of MHC haplotypes. However, we found no evidence of independent genetic effects on the duration of male-female social pairings, male social status (achieving OMU leader male status or not), the number of females with which individual leader males paired, the likelihood of potential male-female pairings producing offspring, or whether males fathered offspring or not. Overall, our findings suggest different genetic factors are involved in social and paternal choice in R. roxellana.

Protocol for the identification and expression analysis of a cytoplasmic membrane-localized protein STING.

Here, we present a protocol for the detection of the two STING isoforms (erSTING and pmSTING) in human peripheral blood mononuclear cells or mouse splenocytes using Western blot and PCR. We detail steps to construct plasmids encoding each isoform and transfer them into mouse and human cell lines. Finally, we describe how to detect cell membrane localization of pmSTING using flow cytometry, immunoprecipitation, and immunofluorescence. This protocol is applicable for proteins with well-predicted topological structures. For complete details on the use and execution of this protocol, please refer to Li et al.1.

Soft landing of polyatomic anions onto three-dimensional semiconductive and conductive substrates.

Soft landing of well-characterized polyoxometalate anions, PW12O40 3- (WPOM) and PMo12O40 3- (MoPOM), was carried out to explore the distribution of anions in the semiconducting 10 and 6 µm-long vertically aligned TiO2 nanotubes as well as 300 µm-long conductive vertically aligned carbon nanotubes (VACNTs). The distribution of soft-landed anions on the surfaces and their penetration into the nanotubes were studied using energy dispersive X-ray spectroscopy (EDX) and scanning electron microscopy (SEM). We observe that soft landed anions generate microaggregates on the TiO2 nanotubes and only reside in the top 1.5 µm of the nanotube height. Meanwhile, soft landed anions are uniformly distributed on top of VACNTs and penetrate into the top 40 µm of the sample. We propose that both the aggregation and limited penetration of POM anions into TiO2 nanotubes is attributed to the lower conductivity of this substrate as compared to VACNTs. This study provides first insights into the controlled modification of three dimensional (3D) semiconductive and conductive interfaces using soft landing of mass-selected polyatomic ions, which is of interest to the rational design of 3D interfaces for electronics and energy applications.

A multiscale functional map of somatic mutations in cancer integrating protein structure and network topology.

A major goal of cancer biology is to understand the mechanisms underlying tumorigenesis driven by somatically acquired mutations. Existing computational approaches focus on either scoring the pathogenicity of mutations or characterizing their effects at specific scales. Here, we established a unified computational framework, NetFlow3D, that systematically maps the multiscale mechanistic effects of somatic mutations in cancer. The establishment of NetFlow3D hinges upon the Human Protein Structurome, a complete repository we first compiled that incorporates the 3D structures of every single protein as well as the binding interfaces for all known PPIs in humans. The vast majority of 3D structural information was resolved by recent deep learning algorithms. By applying NetFlow3D to 415,017 somatic protein-altering mutations in 5,950 TCGA tumors across 19 cancer types, we identified 1,656 intra- and 3,343 inter-protein 3D clusters of mutations throughout the Human Protein Structurome, of which ~50% would not have been found if using only experimentally-determined protein structures. These 3D clusters have converging effects on 377 cellular subnetworks. Compared to canonical PPI network analyses, NetFlow3D achieved a 5.5-fold higher statistical power for identifying significantly dysregulated subnetworks. The majority of identified subnetworks were previously obscured by the overwhelming background noise of non-clustered passenger mutations, including portions of non-canonical PRC1, mediator complex, MCM2-7 complex, neddylation of cullins, complement system, TRiC, etc. NetFlow3D and our pan-cancer results can be accessed from http://netflow3d.yulab.org. This work shows that mapping how individual mutations act across scales requires the integration of their local spatial organization on protein structures and their global topological organization in the PPI network.

Mechanisms underlying capsulotomy for refractory obsessive-compulsive disorder: neural correlates of negative affect processing overlap with deep brain stimulation targets.

Ablative procedures such as anterior capsulotomy are potentially effective in refractory obsessive-compulsive disorder (OCD). Converging evidence suggests the ventral internal capsule white matter tracts traversing the rostral cingulate and ventrolateral prefrontal cortex and thalamus is the optimal target for clinical efficacy across multiple deep brain stimulation targets for OCD. Here we ask which prefrontal regions and underlying cognitive processes might be implicated in the effects of capsulotomy by using both task fMRI and neuropsychological tests assessing OCD-relevant cognitive mechanisms known to map across prefrontal regions connected to the tracts targeted in capsulotomy. We tested OCD patients at least 6 months post-capsulotomy (n = 27), OCD controls (n = 33) and healthy controls (n = 34). We used a modified aversive monetary incentive delay paradigm with negative imagery and a within session extinction trial. Post-capsulotomy OCD subjects showed improved OCD symptoms, disability and quality of life with no differences in mood or anxiety or cognitive task performance on executive, inhibition, memory and learning tasks. Task fMRI revealed post-capsulotomy decreases in the nucleus accumbens during negative anticipation, and in the left rostral cingulate and left inferior frontal cortex during negative feedback. Post-capsulotomy patients showed attenuated accumbens-rostral cingulate functional connectivity. Rostral cingulate activity mediated capsulotomy improvement on obsessions. These regions overlap with optimal white matter tracts observed across multiple stimulation targets for OCD and might provide insights into further optimizing neuromodulation approaches. Our findings also suggest that aversive processing theoretical mechanisms may link ablative, stimulation and psychological interventions.

First report of Fusarium tricinctum Species complex causing root rot of tobacco in China.

Tobacco (Nicotiana tabacum L.) is an economically important crop in China. In June 2021, a root rot disease was observed on tobacco (cv. Yunyan99) in Lushi, Mianchi, and Luoning counties of western Henan, China. Diseased tobacco plants exhibited wilting with leaf chlorosis and root rot accompanied by purplish to brown vascular discoloration. The symptoms were observed in four surveyed fields, 57 ha in total, and disease incidence ranged from 21 to 56%. Five symptomatic plants with leaf chlorosis and root rot were randomly collected from each field for pathogen isolation. Tissue pieces from diseased roots were surface sterilized in 75% ethanol for 30 s then rinsed with sterile distilled water three times, air dried, and placed onto potato dextrose agar (PDA) medium. Five isolates, SL1, SL2, SL3, LN and KC, were purified by single-spore culturing. On PDA, colonies grew at a rate of 2-5 mm/day and produced abundant cottony, white to pink aerial mycelia and rose pigment on the reverse side of the culture plate. From 7-day-old cultures grown on carnation leaf agar (CLA), macroconidia were straight to subarcuate, with blunt and slightly hooked apical and basal cells, had three to four septa, measured 23.4 to 44.6×3.5 to 4.2 µm (n=30). Cylindrical, napiform or oval microconidia were one to two-celled, measuring 6.3 to 22.9×2.2 to 4.9 µm (n=30). Spherical chlamydospores were intercalary or terminal, in chains. Such characteristics resembled those of the Fusarium tricinctum species comples (FTSC; Batra and Lichtwardt 1962; Leslie and Summerell 2006). To confirm the morphological diagnosis, the genomic DNA of the isolates were extracted, the translation elongation factor 1-alpha (EF-1α), RNA polymerase I largest subunit (RPB1) and second largest subunit (RPB2) genes were amplified with primers EF1/EF2, F5/G2R and 5f2/7cr respectively (O'Donnell et al. 2010), and sequenced. Maximum likelihood analysis was carried out using MEGA 7. Sequences were 97.55% to 100% identical to corresponding DNA sequences of FTSC based on GenBank and Fusarium MLST BLASTn analysis, and deposited in GenBank (ON637268.1-ON637272.1, ON637275.1-ON637279.1, ON637282.1-ON637286.1). Based on the morphological characteristics and phylogenetic analysis, the isolates were identified as F. acuminatum (SL1, SL2, SL3 and LN; Senatore et al. 2021) and F. reticulatum (KC; Moreira et al. 2019). Koch's postulates were conducted to verify the pathogenicity of individual isolates. The four-leaf stage healthy tobacco seedlings (Yunyan99, n=30) were inoculated by pouring 20 mL conidial suspension (1×107 conidia/mL) around the rhizosphere. Control seedlings were inoculated with sterilized water (n=30). All the treatments were maintained under greenhouse conditions with a 12-h light/dark photoperiod at 25±0.5℃ and 70% relative humidity for 30 days. The assay was conducted three times. Foliage chlorosis and root rot were observed on the inoculated tobacco seedlings, whereas the control seedlings remained asymptomatic after 30 days. The pathogens were reisolated from the necrotic tissue from all inoculated seedlings and were identified by sequencing partial EF-1α and RPB2 genes. Fusarium tricinctum species complex are known as an important causal of cereals Fusarium Head Blight (FHB; Laraba, et al. 2022). In China, F. acuminatum can also infect herb plants and fruits, such as Angelica sinensis, Schisandra chinensis (Ma et al. 2022; Shen et al. 2021). To our knowledge, this is the first report of root rot on tobacco caused by FTSC members in China as well as the world. This finding expands the host range known for FTSC and will be helpful for developing effective control strategies of tobacco root rot.

Sodium alginate reinforced polyacrylamide/xanthan gum double network ionic hydrogels for stress sensing and self-powered wearable device applications.

Strong and ductile sodium alginate (SA) reinforced polyacrylamide (PAM)/xanthan gum (XG) double network ionic hydrogels were constructed for stress sensing and self-powered wearable device applications. In the designed network of PXS-Mn+/LiCl (short for PAM/XG/SA-Mn+/LiCl, where Mn+ stands for Fe3+, Cu2+ or Zn2+), PAM acts as a flexible hydrophilic skeleton, and XG functions as a ductile second network. The macromolecule SA interacts with metal ion Mn+ to form a unique complex structure, significantly improving the mechanical strength of the hydrogel. The addition of inorganic salt LiCl endows the hydrogel with high electrical conductivity, and meanwhile reduces the freezing point and prevents water loss of the hydrogel. PXS-Mn+/LiCl exhibits excellent mechanical properties and ultra-high ductility (a fracture tensile strength up to 0.65 MPa and a fracture strain up to 1800%), and high stress-sensing performance (a high GF up to 4.56 and pressure sensitivity of 0.122). Moreover, a self-powered device with a dual-power-supply mode, i.e., PXS-Mn+/LiCl-based primary battery and TENG, and a capacitor as the energy storage component was constructed, which shows promising prospects for self-powered wearable electronics.

In Situ Mineralizing Spinning of Strong and Tough Silk Fibers for Optical Waveguides.

Biopolymer-based optical waveguides with low-loss light guiding performance and good biocompatibility are highly desired for applications in biomedical photonic devices. Herein, we report the preparation of silk optical fiber waveguides through bioinspired in situ mineralizing spinning, which possess excellent mechanical properties and low light loss. Natural silk fibroin was used as the main precursor for the wet spinning of the regenerated silk fibroin (RSF) fibers. Calcium carbonate nanocrystals (CaCO3 NCs) were in situ grown in the RSF network and served as nucleation templates for mineralization during the spinning, leading to the formation of strong and tough fibers. CaCO3 NCs can guide the structure transformation of silk fibroin from random coils to ß-sheets, contributing to enhanced mechanical properties. The tensile strength and toughness of the obtained fibers are up to 0.83 ± 0.15 GPa and 181.98 ± 52.42 MJ·m-3, obviously higher than those of natural silkworm silks and even comparable to spider silks. We further investigated the performance of the fibers as optical waveguides and observed a low light loss of 0.46 dB·cm-1, which is much lower than natural silk fibers. We believed that these silk-based fibers with excellent mechanical and light propagation properties are promising for applications in biomedical light imaging and therapy.

Triboelectric nanogenerators assembled by cobalt(II) coordination polymer incorporated composite films and their application for self-powered anticorrosion.

A friction layer with stability and durability is important to promote the practical application of triboelectric nanogenerators (TENGs). In this work, a two-dimensional cobalt coordination polymer (Co-CP) was successfully synthesized using cobalt nitrate, 4, 4', 4''-tricarboxyltriphenylamine and 2,2'-bipyridine. To clarify the effect of the doping proportions of Co-CP and the types of conposite polymers on the output performance of the TENG, Co-CP was combined with two organic polymers having different polarities (polyvinylidene fluoride (PVDF) and ethyl cellulose (EC)) to form a series of composite films, which were used as the friction electrode materials to fabricate TENGs. Electrical characterizations indicated that a high output current and voltage were obtained from the TENG based on 15 wt% Co-CP incorporated in PVDF (Co-CP@PVDF), which could be further improved by the Co-CP@EC composite film at the same doping ratio. Furthermore, the optimally fabricated TENG was demonstrated to prevent electrochemical corrosion of carbon steel.

Spermidine suppresses the activation of hepatic stellate cells to cure liver fibrosis through autophagy activator MAP1S.

BACKGROUND AND AIMS: Liver diseases present a wide range of fibrosis, from fatty liver with no inflammation to steatohepatitis with varying degrees of fibrosis, to established cirrhosis leading to HCC. In a multivariate analysis, serum levels of spermidine were chosen as the top metabolite from 237 metabolites and its levels were drastically reduced along with progression to advanced steatohepatitis. Our previous studies that showed spermidine supplementation helps mice prevent liver fibrosis through MAP1S have prompted us to explore the possibility that spermidine can alleviate or cure already developed liver fibrosis. METHODS: We collected tissue samples from patients with liver fibrosis to measure the levels of MAP1S. We treated wild-type and MAP1S knockout mice with CCl4 -induced liver fibrosis with spermidine and isolated HSCs in culture to test the effects of spermidine on HSC activation and liver fibrosis. RESULTS: Patients with increasing degrees of liver fibrosis had reduced levels of MAP1S. Supplementing spermidine in mice that had already developed liver fibrosis after 1 month of CCl4 induction for an additional 3 months resulted in significant reductions in levels of ECM proteins and a remarkable improvement in liver fibrosis through MAP1S. Spermidine also suppressed HSC activation by reducing ECM proteins at both the mRNA and protein levels, and increasing the number of lipid droplets in stellate cells. CONCLUSIONS: Spermidine supplementation is a potentially clinically meaningful approach to treating and curing liver fibrosis, preventing cirrhosis and HCC in patients.

Menstrual pain mediated the association between daytime sleepiness and suicidal risk: A prospective study.

BACKGROUND: Adolescents with daytime sleepiness have been demonstrated to have a higher level of suicidal risk than those without. Currently, few studies had examined the pathway from daytime sleepiness to suicidal risk among female adolescents. This study aimed to explore the association among menstrual pain, daytime sleepiness, and suicidal risk among female adolescents in China. METHODS: Of 7072 adolescents who participated in the follow-up survey of Shandong Adolescents Behavior & Health Cohort (SABHC), 3001 were female adolescents who had begun to menstruate and included for the analysis. A structured self-administrated questionnaire was used to measure menstrual pain, daytime sleepiness, suicidal risk and demographic characteristics. Participants were first surveyed in November-December 2015 and resurveyed 1 year later. RESULTS: Of 3001 participants, 11.43 % had suicidal risk, 79.8 % experienced menstrual pain. Cross-lagged analysis showed that there was cause-and-effect relationship between menstrual pain and daytime sleepiness. Moderate (OR = 1.79, 95%CI: 1.22-2.63) and severe (OR = 2.73, 95%CI: 1.80-4.12) menstrual pain (follow-up) were associated with suicidal risk (follow-up). Daytime sleepiness (baseline: OR = 1.04, 95%CI: 1.02-1.06, follow-up: OR = 1.07, 95%CI: 1.05-1.09) had effects on suicidal risk (follow-up). Mediation analysis showed that menstrual pain played a partially mediating role between daytime sleepiness and suicidal risk, with the indirect effect being 0.002 (95%CI: 0.001-0.004). LIMITATIONS: All data were self-reported. CONCLUSIONS: Menstrual pain and daytime sleepiness had effects on each other, and they both were the risk factors of suicidal risk. Among female adolescents, the association between daytime sleepiness and suicidal risk could be partially mediated by menstrual pain. Releasing the menstrual pain of female adolescents with daytime sleepiness could reduce their suicidal risk.

Transcriptomic analysis of lipid metabolism in zebrafish offspring of parental long-term exposure to bisphenol A.

Bisphenol A (BPA) is one of the most common environmental endocrine disruptor chemicals (EDCs) and exhibits reproductive, cardiovascular, immune, and neurodevelopmental toxic effects. The development of the offspring was examined in the present investigation to determine the cross-generational effects of long-term exposure of parental zebrafish to environmental concentrations of BPA (15 and 225 µg/L). Parents were exposed to BPA for 120 days, and their offspring were evaluated at 7 days after fertilization in BPA-free water. The offspring exhibited higher mortality, deformity, and heart rates, and showed significant fat accumulation in abdominal region. RNA-Seq data showed that more lipid metabolism-related KEGG pathways, such as the PPAR signaling pathway, adipocytokine signaling pathway, and ether lipid metabolism pathway were enriched in the 225 µg/L BPA-treated offspring compared to 15 µg/L BPA-treated offspring, indicating greater effects of high dose BPA on offspring lipid metabolism. Lipid metabolism-related genes implied that BPA is responsible for disrupting lipid metabolic processes in the offspring through increased lipid production, abnormal transport, and disruption of lipid catabolism. The present study will be helpful for further evaluation of the reproductive toxicity of environmental BPA to organisms and the subsequent parent-mediated intergenerational toxicity.

Dihydromyricetin Inhibits Pseudorabies Virus Multiplication In Vitro by Regulating NF-κB Signaling Pathway and Apoptosis.

Pseudorabies virus (PRV) infections have caused huge economic losses to the breeding industry worldwide, especially pig husbandry. PRV could threaten human health as an easily ignored zoonotic pathogen. The emergence of new mutants significantly reduced the protective effect of vaccination, indicating an urgent need to develop specific therapeutic drugs for PRV infection. In this study, we found that dihydromyricetin (DMY) could dose-dependently restrain PRV infection in vitro with an IC50 of 161.34 µM; the inhibition rate of DMY at a concentration of 500 µM was 92.16 %. Moreover, the mode of action showed that DMY directly inactivated PRV virion and inhibited viral adsorption and cellular replication. DMY treatment could improve PRV-induced abnormal changes of the NF-κB signaling pathway and excessive inflammatory response through regulation of the contents of IκBα and p-P65/P65 and the transcriptional levels of cytokines (TNF-α, IL-1ß and IL-6). Furthermore, DMY promoted the apoptosis of PRV-infected cells through the regulation of the expressions of Bax and Bcl-xl and the transcriptional levels of Caspase-3, Bax, Bcl-2 and Bcl-xl, thereby limiting the production of progeny virus. These findings indicated that DMY could be a candidate drug for the treatment of PRV infection.

Encapsulated Essential Oils Improve the Growth Performance of Meat Ducks by Enhancing Intestinal Morphology, Barrier Function, Antioxidant Capacity and the Cecal Microbiota.

The objective of this study was to evaluate the effects of encapsulated essential oils (EOs) on the gut microbiota, growth performance, intestinal morphology, antioxidant properties and barrier function of meat-type ducks. A total of 320 male Cherry Valley ducks (1 day old), were randomly assigned to four dietary experimental groups with eight replicates of ten ducks each. The groups consisted of the CON group (basal diet), the HEO group (basal diet + EO 1000 mg/kg), the LEO group (basal diet + EO 500 mg/kg), and the ANT group (basal diet + chlortetracycline 50 mg/kg). Our findings indicated that ducks fed with EO 1000 mg/kg had greater average daily feed intake (ADFI), average daily gain (ADG), and body weight (BW) and a lower feed conversion ratio (FCR) than the other groups. The serum concentration of TG reduced in the HEO (p > 0.05) and LEO (p < 0.05) groups on day 42, while the concentration of CHOL increased with the EO concentration in the LEO (p > 0.05) and HEO (p < 0.05) groups. No differences were observed in the ileal mucosa for the activities of SOD, MPO and GSH-PX after EO dietary treatment. Dietary supplementation with EOs significantly increased the villus heights (p < 0.01) and the ratio of villus height to crypt depth (c/v) in the duodenum and jejunum of ducks. Moreover, the mRNA expressions of Claudin1 and Occludin in the jejunal mucosa were observed to be higher in the LEO and HEO groups rather than the CON and ANT groups on d 42. The α diversity showed that the HEO group improved the bacterial diversity and abundance. The ß diversity analysis indicated that the microbial structures of the four groups were obviously separated. EO dietary supplementation could increase the relative abundance (p < 0.01) of the Bacteroidetes phylum, Bacteroidaceae family, and Bacteroides, Desulfovibrio, Phascolarctobacterium, and Butyricimonas genera in the cecal microbiota of ducks. We demonstrated significant differences in the bacterial composition and functional potential of the gut microbiota in ducks that were fed either an EO diet or a basal diet. Therefore, supplemented EOs was found to have a positive effect on the growth performance and intestinal health of ducks, which was attributed to the improvement in cecal microbiota, intestinal morphology, and barrier function.

α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In Vivo.

Inflammation is an important risk factor for bone-destroying diseases. Our preliminary research found that Zanthoxylum bungeanum seed oil (ZBSO) is abundant in unsaturated fatty acids and could inhibit osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW264.7 cells. However, the key constituents in ZBSO in the prevention of osteoclastogenesis and its possible mechanism related to inflammation are still unclear. Therefore, in this study, oleic acid (OA), linoleic acid (LA), palmitoleic acid (PLA), and alpha-linolenic acid (ALA) in ZBSO, havingthe strongest effect on RANKL-induced osteoclastogenesis, were selected by a tartrate-resistant acid phosphatase (TRAP) staining method. Furthermore, the effects of the selected fatty acids on anti-inflammation and anti-osteoclastogenesis in vitro and in vivo were assessed using RT-qPCR. Among the four major unsaturated fatty acids we tested, ALA displayed the strongest inhibitory effect on osteoclastogenesis. The increased expression of free fatty acid receptor 4 (FFAR4) and ß-arrestin2 (ßarr2), as well as the decreased expression of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), nuclear factor of activated T-cells c1 (NFATc1), and tartrate-resistant acid phosphatase (TRAP) in RAW264.7 cells after ALA treatment were observed. Moreover, in ovariectomized osteoporotic rats with ALA preventive intervention, we found that the expression of TNF-α, interleukin-6 (IL-6), interleukin-1ß (IL-1ß), NFATc1, and TRAP were decreased, while with the ALA therapeutic intervention, downregulated expression of NF-κB, NFATc1, TRAP, and transforming growth factor beta-activated kinase 1 (TAK1) were noticed. These results indicate that ALA, as the major unsaturated fatty acid in ZBSO, could inhibit RANKL-induced osteoclastogenesis via the FFAR4/ßarr2 signaling pathway and could prevent inflammation, suggesting that ZBSO may be a promising potential natural product of unsaturated fatty acids and a dietary supplement for the prevention of osteoclastogenesis and inflammatory diseases.

Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life.

Introduction: Asthma is primarily divided into two categories: type 2 (T2-high) and non-type 2 (T2-low). A relationship between asthma severity and vitamin D deficiency has been identified, but its impact on each asthma endotype remains unknown. Methods: We clinically examined the influence of vitamin D on patients with T2-high (n = 60) or T2-low asthma (n = 36) compared with controls (n = 40). Serum 25(OH)D levels, inflammatory cytokines and spirometry were measured. Mouse models were then used to further analyze the effects of vitamin D on both asthmatic endotypes. BALB/c mice were fed with vitamin D-deficient (LVD), -sufficient (NVD), or -supplemented diets (HVD) throughout lactation and offspring followed the same diet after weaning. Offspring were sensitized/challenged with ovalbumin (OVA) to establish "T2-high" asthma or OVA combined with ozone exposure (OVA + ozone) to induce "T2-low" asthma. Spirometry and serum, bronchoalveolar lavage fluid (BALF), and lung tissues were analyzed. Results: Serum 25(OH)D levels were decreased in asthmatic patients compared with controls. Patients with vitamin D deficiency (Lo) had varying degrees of elevation of the pro-inflammatory cytokines IL-5, IL-6, and IL-17A, decreased expression of the anti-inflammatory cytokine IL-10, and altered forced expiratory volume in the first second as a percentage of predicted value (FEV1%pred) in both asthmatic endotypes. Vitamin D status had a stronger correlation with FEV1%pred in T2-low asthma than T2-high asthma, and 25(OH)D level was only positively linked to maximal mid-expiratory flow as a percentage of predicted value (MMEF%pred) in the T2-low group. Inflammation, hyperresponsiveness, and airway resistance (RL) was increased in both asthma models compared with controls while vitamin D deficiency further increased airway inflammation and airway obstruction. These findings were particularly prominent in T2-low asthma. Discussion: The potential function and mechanisms of vitamin D and both asthma endotypes should be studied individually, and further analysis of the potential signaling pathways involved with vitamin D on T2-low asthma is warranted.

Efficacy evaluation and influencing factor analysis of postoperative 131I for the treatment of primary hyperthyroidism combined with differentiated thyroid cancer (DTC)-a retrospective cohort study.

Background: 131I treatment is one of the important methods of comprehensive postoperative treatment for patients with hyperthyroidism complicated with differentiated thyroid cancer (DTC). Early identification of patients with poor treatment efficacy of 131I is particularly important. Current studies mainly focus on the relationship between hyperthyroidism and the occurrence and development of DTC, and there are few studies on the factors affecting the curative effect. The purpose of this study was to find the influencing factors of efficacy evaluation and provide evidence for early identification of patients with poor efficacy in DTC combined with primary hyperthyroidism patients. Methods: This was a retrospective analysis of DTC patients with primary hyperthyroidism who received 131I treatment in our department from 2012 to 2021. Follow-up intervals were 3 months within 1 year, 6 months within 1 to 2 years, and annual follow-up thereafter, the median follow-up time was 12.0 (3.0, 24.0) months. Serological examination and imaging examination were used to evaluate the efficacy. Patients were classified into an excellent response (ER) group and a non-ER group based on treatment response more than 6 months after 131I treatment. Univariate analysis and multivariate logistic regression analysis were performed on the basic clinical characteristics, pathological characteristics and curative effect of the patients, in order to find independent risk factors affecting the curative effect. Results: Eighty-nine patients were mostly female (80.9%), the average age was 43.47±11.88 years old, and tumor size was 1.2 (0.75, 1.80) cm, 56 patients (62.9%) in the ER group. psTg [odds ratio (OR): 1.325; 95% confidence interval (CI): 1.135-1.547; P<0.001], maximum tumor diameter (OR: 2.428; 95% CI: 1.392-4.235; P=0.002) and pathology-confirmed combined HT (OR: 8.669; 95% CI: 1.877-40.038; P=0.006) were independent risk factors for predicting ER. Conclusions: Our findings demonstrate that most hyperthyroidism combined with DTC patients could get favorable clinical outcomes from 131I treatment. The tumor diameter, pathology-confirmed diagnosis of combined HT, and psTg level can be used to identify patients who can get ER by the effect of 131I in hyperthyroidism combined with DTC at an early stage.