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Based on the hexagonal honeycomb structure and the tri-ligament chiral honeycomb structure, this paper proposes a hybrid material structure with low-frequency elastic wave suppression below 100 Hz. Based on the finite element method and Bloch's theorem, the energy band structure was calculated, and the formation of the band gap and the wave-propagation properties of the structure were carefully studied, the wave attenuation performance of the composite structure was simulated, and the influence of material properties and geometric parameters on the width and position of the band-gap distribution was discussed. The results show that the structure can generate a good band gap in the low-frequency range of 100 Hz, and the wave propagation is suppressed obviously. Demonstrating its potential in practical applications, the research in this paper provides a theoretical basis for the manufacture of low-frequency vibration damping equipment and instruments, and provides a scheme for the design of metamaterials with low-frequency band gaps. [ABSTRACT FROM AUTHOR]

Scutellarin, one of natural flavonoids from Scutellaria barbata D. Don and Erigeron breviscapus (vant) Hand.-Mazz. Modern pharmacological studies have shown that scutellarin has a good anti-tumor effect. According to the literature review at home and abroad, scutellarin can inhibit the growth and metastasis of tumor cells, block the cell cycle at various stages, induce apoptosis and autophagy, interfere with tumor metabolism, reverse drug resistance of tumor cells and enhance the sensitivity of chemotherapy drugs. In this paper, the anti-tumor mechanism of scutellarin was reviewed, and the shortcomings of current studies and future research directions were analyzed, so as to provide a basis for further exploration of the anti-tumor potential of scutellarin and its further development and utilization. [ABSTRACT FROM AUTHOR]

This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known neurodegenerative disease. We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia, Parkinsonism, and cognitive function, as well as brain magnetic resonance imaging scans with seven sequences. We searched for co-segregations of abnormal repeat-expansion loci, pathogenic variants in known spinocerebellar ataxia-related genes, and novel rare mutations via whole-genome sequencing and linkage analysis. A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay. This pedigree presented novel late-onset core characteristics including cerebellar ataxia, Parkinsonism, and pyramidal signs in all nine affected members. Brain magnetic resonance imaging showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus, and hypo-intensities of the cerebellar dentate nuclei, basal ganglia, mesencephalic red nuclei, and substantia nigra, all of which suggested neurodegeneration. Whole-genome sequencing identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, meanwhile, exhibited none of the known repeat-expansions or point mutations in pathogenic genes. Remarkably, this CARS mutation causes a 20% decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type. All family members carrying a heterozygous mutation CARS (E795V) had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia. These findings identify novel pathogenesis of Parkinsonism-spinocerebellar ataxia and provide insights into its genetic architecture. [ABSTRACT FROM AUTHOR]

Purpose: It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs). Methods: MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs. Results: A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37-0.84, p=0.006) and a slower decline in eGFR (WMD = 0.90mL/min/1.73 m2, 95% CI 0.31-1.48, p=0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD=-0.21, 95% CI -0.41 to -0.01, p=0.042). Conclusion: Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout. Systematic review registration: PROSPERO CRD42021272591 [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1‐nitropyrene (1‐NP), a key component of motor vehicle exhaust, on autism‐like behaviors in a mouse model. Three‐chamber test finds that prenatal 1‐NP exposure causes autism‐like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1‐NP‐exposed weaning pups. Immunofluorescence finds that prenatal 1‐NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1‐NP exposure retards tangential migration of GAD67‐positive interneurons and downregulates interneuron migration‐related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1‐NP exposure reduces hydroxymethylation of interneuron migration‐related genes through inhibiting ten‐eleven translocation (TET) activity in fetal forebrain. Supplement with alpha‐ketoglutarate (α‐KG), a cofactor of TET enzyme, reverses 1‐NP‐induced hypohydroxymethylation at specific sites of interneuron migration‐related genes. Moreover, α‐KG supplement alleviates 1‐NP‐induced migration retardation of interneurons in fetal forebrain. Finally, maternal α‐KG supplement improves 1‐NP‐induced autism‐like behaviors in weaning offspring. In conclusion, prenatal 1‐NP exposure causes autism‐like behavior partially by altering DNA hydroxymethylation of interneuron migration‐related genes in developing brain. [ABSTRACT FROM AUTHOR]

Introduction: Peach (Prunus persica) has a high nutritional and economic value. However, its overgrowth can lead to yield loss. Regulating the growth of peach trees is challenging. The small auxin-up RNA (SAUR) gene family is the largest family of auxin-responsive genes, which play important roles in plant growth and development. However, members of this gene family are rarely reported in peach. Methods: In this study, we measured leaf area, chlorophyll and lignin content to detect the role of PpSAUR5 on growth through transgenic Arabidopsis. Results: PpSAUR5 responds to auxin and gibberellin, promoting and inhibiting the synthesis of gibberellin and auxin, respectively. The heterologous transformation of PpSAUR5 in Arabidopsis led to enhanced growth of leaves and siliques, lightening of leaf color, decrease in chlorophyll content, increase in lignin content, abnormalities in the floral organs, and distortion of the inflorescence axis. Transcriptome data analysis of PpSAUR5 overexpression and wild-type lines revealed 854 differentially expressed genes (DEGs). GO and KEGG analyses showed that the DEGs were primarily involved in biological processes, such as cellular processes, metabolic processes, response to stimuli, and catalytic activity. These genes were mainly enriched in pathways, such as phenylalanine biosynthesis, phytohormone signaling, and MAPK signaling. Discussion: In summary, these results suggested that PpSAUR5 might regulate tree vigor by modulating the synthesis of auxin and gibberellin. Future studies can use PpSAUR5 as a candidate gene to elucidate the potential regulatory mechanisms underlying peach tree vigor. [ABSTRACT FROM AUTHOR]

Background: Pruning is an important cultivation management option that has important effects on peach yield and quality. However, the effects of pruning on the overall genetic and metabolic changes in peach leaves and fruits are poorly understood. Results: The transcriptomic and metabolomic profiles of leaves and fruits from trees subjected to pruning and unpruning treatments were measured. A total of 20,633 genes and 622 metabolites were detected. Compared with those in the control, 1,127 differentially expressed genes (DEGs) and 77 differentially expressed metabolites (DEMs) were identified in leaves from pruned and unpruned trees (pdLvsupdL), whereas 423 DEGs and 29 DEMs were identified in fruits from the pairwise comparison pdFvsupdF. The content of three auxin analogues was upregulated in the leaves of pruned trees, the content of all flavonoids detected in the leaves decreased, and the expression of almost all genes involved in the flavonoid biosynthesis pathway decreased. The phenolic acid and amino acid metabolites detected in fruits from pruned trees were downregulated, and all terpenoids were upregulated. The correlation analysis revealed that DEGs and DEMs in leaves were enriched in tryptophan metabolism, auxin signal transduction, and flavonoid biosynthesis. DEGs and DEMs in fruits were enriched in flavonoid and phenylpropanoid biosynthesis, as well as L-glutamic acid biosynthesis. Conclusions: Pruning has different effects on the leaves and fruits of peach trees, affecting mainly the secondary metabolism and hormone signalling pathways in leaves and amino acid biosynthesis in fruits. [ABSTRACT FROM AUTHOR]

Pneumoconiosis is a common occupational disease that can worsen with accompanying infection. Torque teno virus (TTV) is a prevalent human virus with multiple genotypes that can chronically and persistently infect individuals. However, the prevalence of TTV in pneumoconiosis patients is still unclear. This research aims to detect the presence and prevalence of TTV in the alveolar lavage fluid of pneumoconiosis patients in the Hunan Province of China using PCR. As a result, a 65.5% positive rate (19 out of 29) of TTV was detected. The TTV detection rate varies among different stages of silicosis and different pneumoconiosis patient ages. Nine novel TTV genomes ranging in size from 3719 to 3908 nt, named TTV HNPP1, HNPP2, HNPP3, HNPP4, HNPP5, HNPP6-1, HNPP6-2, HNPP7-1 and HNPP7-2, were identified. A genomic comparison and phylogenetic analysis indicated that these nine TTVs represent five different species with high genetic diversity which belong to the genus Alphatorquevirus. HNPP6-1 and HNPP6-2 belong to TTV3, HNPP5 belongs to TTV13, HNPP1 belongs to TTV24, HNPP4 belongs to TTV20, and the others belong to TTV19. The genomes of TTV HNPP1, HNPP6-1, and HNPP6-2 contain three putative open reading frames (ORFs) coding for proteins, ORF1, ORF2, and ORF3, while the other six TTV genomes contain two ORFs coding for proteins, ORF1 and ORF2. These results provide the first description of TTV epidemiology in pneumoconiosis patients in China. The newly identified TTV genome sequences reveal the high genetic diversity of TTV in pneumoconiosis patients and could contribute to a deeper understanding of TTV retention and infection in humans. [ABSTRACT FROM AUTHOR]

Main conclusion: Overexpression of MdLBD3 in Arabidopsis reduced sensitivity to salt and drought stresses and was instrumental in promoting early flowering. Salt and drought stresses have serious effects on plant growth. LATERAL ORGAN BOUNDARY DOMAIN (LBD) proteins are a plant-specific transcription factors (TFs) family and play important roles in plants in resisting to abiotic stress. However, about the function of LBDs in apple and other woody plants is little known. In this study, protein sequences of the LBD family TFs in apples were identified which contained conserved LOB domains. The qRT-PCR analysis showed that the MdLBD3 gene was widely expressed in various tissues and organs. The subcellular localization assay showed that the MdLBD3 protein was localized in the nucleus. Ectopic expression of MdLBD3 in Arabidopsis positively regulated its salt and drought resistance, and promoted early flowering. Collectively, these results showed that MdLBD3 improved the abiotic stress resistance, plant growth and development. Overall, this study provided a new gene for breeding that can increase the abiotic stress tolerance in apple. [ABSTRACT FROM AUTHOR]

Developing skeletal editing tools is not a trivial task, and realizing the corresponding single-atom transmutation in a ring system without altering the ring size is even more challenging. Here, we introduce a skeletal editing strategy that enables polycyclic arenols, a highly prevalent motif in bioactive molecules, to be readily converted into N-heteroarenes through carbon–nitrogen transmutation. The reaction features selective nitrogen insertion into the C–C bond of the arenol frameworks by azidative dearomatization and aryl migration, followed by ring-opening, and ring-closing (ANRORC) to achieve carbon-to-nitrogen transmutation in the aromatic framework of the arenol. Using widely available arenols as N-heteroarene precursors, this alternative approach allows the streamlined assembly of complex polycyclic heteroaromatics with broad functional group tolerance. Finally, pertinent transformations of the products, including synthesis complex biheteroarene skeletons, were conducted and exhibited significant potential in materials chemistry. Developing skeletal editing tools, especially to realize the single-atom transmutation in a ring system without altering the ring size is challenging. Here, the authors introduce a skeletal editing strategy that enables polycyclic arenols to be readily converted into N-heteroarenes through carbon–nitrogen transmutation. [ABSTRACT FROM AUTHOR]

Objective To understand the prevalence and annual change trend of Internet addiction among students aged 11 and 22 in Inner Mongolia in 2019 and 2021, and to explore the influencing factors of Internet addiction behavior, so as to provide reference basis for the prevention of Internet addiction among students. Methods Students were selected from 12 cities of Inner Mongolia Autonomous Region by stratified cluster random sampling. Internet addiction disorder was determined according to the items of "surveillance and intervention of common diseases and health influencing factors of students in China". Logistic regression method was used to analyze the relationship between Internet addiction and behavioral factors. Results The prevalence of Internet addiction among students aged 11 to 22 years in Inner Mongolia in 2019 was 1.92%, 2.50%, and 2.21%, respectively. Logistic regression analysis showed that vocational high school (OR=1.347, 95%CI: 1.083-1.675), single parent family (OR=1.279, 95% CI: 1.090-1.500), reconstituted family (OR=1326, 95% CI: 1.041-1.690), bullying (OR=1.755, 95% CI: 1.443-2.135), depression (OR=3.557, 95% CI: 3.146-4.021), fighting (OR=3.374, 95% CI: 2.512-4.531), sugary drinks (OR=2.182. 95% CI:1.753-2.716), and eating fried food (OR=2.398, 95% CI: 1.908-3.014) were the risk factor of Internet addiction. Outdoor activities for 2 hours (OR= 0.620, 95% CI: 0.530-0.726), non-smoking (OR=0.553, 95% CI: 0.476-0.643), and non-drinking (OR=0.581, 95% CI: 0.507-0.666) were the protective factors of Internet addiction. Conclusion The current situation of Internet addiction among students in Inner Mongolia is not optimistic. Attention should be paid to bullying, depression, reconstituted families, fighting students, and vocational high school students. Outdoor activities for 1 to 2 hours a day, reducing the intake of sugary drinks and fried foods, and no smoking and drinking can effectively reduce the incidence of Internet addiction. [ABSTRACT FROM AUTHOR]

A new cyclohexenone derivative, phomopine (1), together with five known compounds (2-6) were isolated from Phomopsis sp. XM-01. The structure of 1 was determined by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculation. In vitro bioassays, compounds 1 and 2 exhibited potent antimicrobial activities against Candida albicans and Staphylococcus aureus with their corresponding minimum inhibitory concentrations (MICs) of 64 μg/mL and 16 μg/mL, respectively. [ABSTRACT FROM AUTHOR]

Background: Microglia-mediated neuroinflammation in Alzheimer's disease (AD) is not only a response to pathophysiological events, but also plays a causative role in neurodegeneration. Cytoplasmic cysteinyl-tRNA synthetase (CARS) is considered to be a stimulant for immune responses to diseases; however, it remains unknown whether CARS is involved in the pathogenesis of AD. Methods: Postmortem human temporal cortical tissues at different Braak stages and AD patient-derived serum samples were used to investigate the changes of CARS levels in AD by immunocytochemical staining, real-time PCR, western blotting and ELISA. After that, C57BL/6J and APP/PS1 transgenic mice and BV-2 cell line were used to explore the role of CARS protein in memory and neuroinflammation, as well as the underlying mechanisms. Finally, the associations of morphological features among CARS protein, microglia and dense-core plaques were examined by immunocytochemical staining. Results: A positive correlation was found between aging and the intensity of CARS immunoreactivity in the temporal cortex. Both protein and mRNA levels of CARS were increased in the temporal cortex of AD patients. Immunocytochemical staining revealed increased CARS immunoreactivity in neurons of the temporal cortex in AD patients. Moreover, overexpression of CARS in hippocampal neurons induced and aggravated cognitive dysfunction in C57BL/6J and APP/PS1 mice, respectively, accompanied by activation of microglia and the TLR2/MyD88 signaling pathway as well as upregulation of proinflammatory cytokines. In vitro experiments showed that CARS treatment facilitated the production of proinflammatory cytokines and the activation of the TLR2/MyD88 signaling pathway of BV-2 cells. The accumulation of CARS protein occurred within dense-core Aβ plaques accompanied by recruitment of ameboid microglia. Significant upregulation of TLR2/MyD88 proteins was also observed in the temporal cortex of AD. Conclusions: The findings suggest that the neuronal CARS drives neuroinflammation and induces memory deficits, which might be involved in the pathogenesis of AD. [ABSTRACT FROM AUTHOR]

There is limited evidence on the associations of unintended pregnancy with autism spectrum disorders (ASD). This study aimed to examine this relationship and the modification of pre‐conceptional and prenatal folic acid supplements. Six thousand and five toddlers aged 16 to 30 months from seven cities of six provinces in China were eligible for participation. Information on unintended pregnancy and folic acid supplements was obtained via questionnaires from caregivers of toddlers. The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5) and the Chinese version of the Childhood Autism Rating Scale (CARS). Of the 6005 toddlers in the study (3337 boys and 2668 girls), 71 (1.18%) received the diagnosis of ASD. Generalized linear models with a logit link function showed unintended pregnancy was positively associated with ASD (odds ratios [OR] = 1.69, 95% confidence interval [CI], 1.05–2.79). Stratified estimates indicated that the association remained stable among toddlers of mothers without pre‐conceptional and prenatal folic acid supplements (OR = 2.75, 95% CI, 1.04–7.27; n = 1243, 20.70%). Unintended pregnancy was associated with higher odds of ASD in 16–30 months of toddlers, and the association was consistent among toddlers of mothers without prenatal folic acid supplements. Our findings emphasize the need to raise awareness of the risk of unintended pregnancy and the benefits of folic acid supplements among Chinese women. Lay Summary: The relationship between unintended pregnancy and autism spectrum disorders (ASD), as well as the effects of modifying pre‐conceptional and prenatal folic acid supplements, has not been examined in China. We found unintended pregnancy was positively associated with ASD in toddlers aged 16–30 months from a nationwide cross‐section study. Folic acid supplements during preconception and pregnancy might reduce the impact of unintended pregnancy on the ASD of offspring. [ABSTRACT FROM AUTHOR]

Introduction: Walnut blight is a serious bacterial disease that affects the yield and quality of walnuts. Pantoea agglomerans is one of the main causative agents of walnut blight. However, there have been few studies on the response of walnuts to P. agglomerans infection. Methods: In this study, the soluble sugar, photosynthesis, antioxidant enzyme activities, and secondary metabolites were measured, and the transcriptomic analysis was performed to determine the response of walnut tissue cultures to P. agglomerans infection. Results: After pathogen inoculation, the soluble sugar content decreased, and photosynthesis was inhibited. Antioxidant enzyme (superoxide dismutase and peroxidase) activities and secondary metabolites (phenol and flavonoid) contents increased, especially in the early stages of inoculation. Transcriptomic analysis revealed that the phenylpropanoid biosynthesis pathway is induced after infection, and pathogen infection promotes ABA and ethylene signal transduction and inhibits auxin signaling. In addition, SA and JA-related gene expression was altered after inoculation with P. agglomerans, and the FLS- and calcium-mediated disease resistance signaling pathways were activated. Furthermore, our results suggested an involvement of the R-protein RPMmediated disease resistance pathway in the response of walnuts to bacterial infections. Discussion: Our findings indicated that phenylpropanoid biosynthesis, hormone signal transduction, and plant-pathogen interaction have key roles in pathogenic inoculation, which provide insights into the molecular mechanisms in the response of walnuts to P. agglomerans infection. [ABSTRACT FROM AUTHOR]

Purpose: Reduced slow wave sleep (SWS) has been linked to hypertension in some studies. The aim of the study is to investigate the association between SWS and office blood pressure (BP) in non-hypertensive obstructive sleep apnea (OSA). Methods: This is a retrospective study of 3350 patients who underwent polysomnography (PSG) in our hospital. Based on quartiles of percent SWS, participants were classified into four groups. BP was measured manually on the randomly chosen arm in a seated position with sphygmomanometer after PSG in the morning, and the average of the second and third measurements was used for this analysis. Elevated office BP was defined as a systolic BP≥140 mmHg or diastolic BP≥90 mmHg. Results: There were 1365 patients with OSA and 597 primary snorers included in our study. In OSA group, OSA patients with SWS <13.5% had a significant elevated risk with elevated office BP (OR,1.49[95%CI 1.05-2.10], P=0.025), compared to the highest quartile (percent SWS >39.2%). However, no significant relationship between decreased SWS and elevated office BP was found in primary snorers group. Conclusion: In non-hypertensive OSA patients, decreased SWS is associated with elevated office BP. This is the first study to investigate the association between decreased SWS and incident elevated office BP in non-hypertensive OSA patients. Our results found that in non-hypertensive OSA patients, decreased SWS is associated with elevated office BP. The relationship between decreased SWS and elevated office BP in OSA patients was evident especially in men and in those <60 years old. [ABSTRACT FROM AUTHOR]

Objective To study the impact of the home literacy environment on children's emotional regulation skills and the mediating role of the parent-child relationship between them. Methods A stratified cluster sampling approach was employed to select 1 626 preschool children from five kindergartens in Nanjing. Questionnaires were used to collect detailed information on the home literacy environment, children's emotional regulation skills, and the parent- child relationship. A mediation model was established using the Process program in SPSS macro, and the significance of the mediation effect was tested using the Bootstrap method. Results The findings revealed a positive correlation between the home literacy environment and children's emotional regulation skills (r=0.217, P<0.001), as well as parent- child intimacy (r=0.065, P<0.01). Conversely, a negative correlation was found between the home literacy environment and parent-child conflict (r=-0.129, P<0.001). Additionally, parent-child conflict demonstrated a negative correlation with children's emotional regulation skills (r=-0.443, P<0.001), while parent-child intimacy exhibited a positive correlation (r=0.247, P<0.001). The home literacy environment exerted a significant direct effect on children's emotional regulation skills (β =0.162, P<0.001), and the mediating effect of the parent-child relationship accounted for 25.54% of the total effect. Conclusions The home literacy environment significantly influences children's emotional regulation skills, with the parent-child relationship partially mediating this relationship. [ABSTRACT FROM AUTHOR]

The aging of the world population and increasing stress levels in life are the major cause of the increased incidence of neurological disorders. Alzheimer's disease (AD) creates a huge burden on the lives and health of individuals and has become a big concern for society. Triterpenoid saponins (TS), representative natural product components, have a wide range of pharmacological bioactivities such as anti‐inflammation, antioxidation, antiapoptosis, hormone‐like, and gut microbiota regulation. Notably, some natural TS exhibited promising neuroprotective activity that can intervene in AD progress, especially in the early stage. Recently, studies have indicated that TS play a pronounced positive role in the prevention and treatment of AD. This review discusses the recent research on the neuroprotection of TS and proceeds to detail the action mechanisms of TS against AD, hoping to provide a reference for drug development for anti‐AD. [ABSTRACT FROM AUTHOR]

The microstructure of a compressed explosive solid is closely related to its shock sensitivity and mechanical properties. In this study, ultra-small-angle and small-angle X-ray scattering (USAXS and SAXS) techniques were combined to explore the hierarchical microstructure of die-pressed 2,4,6-trinitro-1,3,5-benzenetriamine (TATB) discs obtained from nanostructured TATB (nano-TATB) powder as the precursor. Using the Guinier-Porod model, the pseudo-invariants, and Porod's law, this study analyzed the microstructures of the materials on a nanometer scale to track the changes in void size, porosity, and interfacial area, which reflected the response of TATB under applied pressures of 1, 2, 5, 10, 15 kN and 30 kN. Results show that there existed three populations of voids in the measured q range. The intergranular voids with sizes of tens of nanometers were sensitive to low pressures (<15 kN) and presented a smooth interface with the TATB matrix. The intragranular voids with sizes of 7–8 nm exhibited a fairly small volume-filling ratio under high pressures (>15 kN), as indicated by the decrease in the volume fractal dimension. Porosities of the voids with sizes of 1–900 nm, which were determined by the pseudoinvariants obtained from the scattering data, decreased from 6% to 1% as the pressures increased from 1 kN to 30 kN. The response of these structural parameters to external pressures implies that the main densification mechanisms under die compression include the flow, fracturing, and plastic deformation of the TATB granules. This study provides a direct insight into the structural evolution of TATB during compression. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between infant feeding practices and autism spectrum disorder (ASD) among children aged 2–5 years in the United States (US). Methods: Data from the 2016–2020 National Survey of Children's Health, a nationally representative cross-sectional survey, were utilized for this study. Questionnaires were administered to parents of children aged 2–5 years to gather information on ASD diagnosis, infant feeding practices, and demographic factors (e.g., child sex, ethnic group, and maternal age at birth). Logistic regression with sample weights was employed to assess the association between infant feeding practices and ASD, while controlling for demographic variables. Polynomial regression models were used to examine trends in exclusive breastfeeding and ever breastfeeding rates among children with and without ASD. Results: A total of 35,050 children aged 2–5 years were analyzed, including 616 diagnosed with ASD, after excluding participants with missing information on breastfeeding and ASD diagnosis. Of these children with ASD, 76.6% (n = 472) had a breastfeeding history, with 67.5% (n = 416) engaged in partial breastfeeding and 9.1% (n = 56) exclusively breastfed. Adjusted odds ratios for each additional month of breastfeeding compared to never being breastfed were 0.98 (95% CI, 0.96–1.01). The adjusted odds ratios for breastfeeding durations of > 0–6 months, > 6–12 months, > 12–24 months, and > 24 months were 0.81 (95% CI, 0.50–1.31), 0.65 (95% CI, 0.36–1.18), 0.81 (95% CI, 0.44–1.49), and 0.48 (95% CI, 0.23–1.01), respectively. Compared to children who were never breastfed, the adjusted odds ratio for children who were ever breastfed was 0.74 (95% CI, 0.47–1.18). Among children with ASD, the proportion of ever breastfeeding declined from 82.0% in 2017 to 64.3% in 2020, while exclusive breastfeeding decreased from 12.0% in 2016 to 4.2% in 2020. Conclusions and relevance: Although no significant association was found between infant feeding practices and ASD among US children aged 2–5 years, the rates of breastfeeding, particularly exclusive breastfeeding, were suboptimal among children with ASD. This highlights the need for specific policies and practices to promote and support breastfeeding among parents of children with ASD or those at high risk of having a child with ASD. [ABSTRACT FROM AUTHOR]

Background: Behavioral research has shown that children with autism spectrum disorder (ASD) have a higher empathizing–systemizing difference (D score) than normal children. However, there is no research about the neuroanatomical mechanisms of the empathizing–systemizing difference in children with ASD. Methods: Participants comprised 41 children with ASD and 39 typically developing (TD) children aged 6‒12 years. Empathizing–systemizing difference was estimated using the D score from the Chinese version of Children's Empathy Quotient and Systemizing Quotient. We quantified brain morphometry, including global and regional brain volumes and surface-based cortical measures (cortical thickness, surface area, and gyrification) via structural magnetic resonance imaging. Results: We found that the D score was significantly negatively associated with amygdala gray matter volume [β = −0.16; 95% confidence interval (CI): −0.30, −0.02; P value = 0.030] in children with ASD. There was a significantly negative association between D score and gyrification in the left lateral occipital cortex (LOC) in children with ASD (B = −0.10; SE = 0.03; cluster-wise P value = 0.006) and a significantly positive association between D score and gyrification in the right fusiform in TD children (B = 0.10; SE = 0.03; cluster-wise P value = 0.022). Moderation analyses demonstrated significant interactions between D score and diagnosed group in amygdala gray matter volume (β = 0.19; 95% CI 0.04, 0.35; P value = 0.013) and left LOC gyrification (β = 0.11; 95% CI 0.05, 0.17; P value = 0.001) but not in right fusiform gyrification (β = 0.08; 95% CI −0.02, 0.17; P value = 0.105). Conclusions: Neuroanatomical variation in amygdala volume and gyrification of LOC could be potential biomarkers for the empathizing–systemizing difference in children with ASD but not in TD children. Large-scale neuroimaging studies are necessary to test the replicability of our findings. [ABSTRACT FROM AUTHOR]

Background: Despite extensive research evaluating the association between prenatal exposure to secondhand smoke (SHS) and the development of autism spectrum disorders (ASD), no study has investigated the association by considering the pre-conceptional period. This study aimed to investigate the associations of pre-conceptional and prenatal SHS exposure and the development of ASD among toddlers. Methods: In this cross-sectional study, parents of 6049 toddlers aged 16–30 months were recruited from 7 tertiary hospitals, 21 communities, and 7 kindergartens located in seven cities in six provinces from five geographical regions of China. We analyzed the associations of SHS exposure and the odds of ASD among toddlers in different exposure windows (pre-conceptional and/or prenatal periods). Data were analyzed from November 2021 to January 2022. Results: Among the 6049 toddlers included in the analysis [22.7 (4.1) months; 44.8% girls], 71 were identified and diagnosed with ASD. Compared with the unexposed toddlers, toddlers with pre-conceptional SHS exposure had higher odds of ASD (OR 2.30, 95% CI 1.36–3.84), while we observed a non-significantly positive association regarding prenatal SHS exposure. When considering both pre-conceptional and prenatal periods, toddlers who were continuously exposed to SHS during these two periods had higher odds than those without SHS exposure (OR 2.32, 95% CI 1.24–4.14). Conclusion: We reported positive SHS–ASD associations when exposed during the pre-conceptional period and continuously exposed during pre-conceptional and prenatal periods, emphasizing the critical window of pre-conception for targeted intervention on smoking. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the associations between particulate matter (PM), lung function and Impulse Oscillometry System (IOS) parameters in chronic obstructive pulmonary disease (COPD) patients and identity effects between different regions in Beijing, China. Methods: In this retrospective study, we recruited 1348 outpatients who visited hospitals between January 2016 and December 2019. Ambient air pollutant data were obtained from the central monitoring stations nearest the participants' residential addresses. We analyzed the effect of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) exposure on lung function and IOS parameters using a multiple linear regression model, adjusting for sex, smoking history, education level, age, body mass index (BMI), mean temperature, and relative humidity. Results: The results showed a relationship between PM2.5, lung function and IOS parameters. An increase of 10 µg/m3 in PM2.5 was associated with a decline of 2.083% (95% CI: −3.047 to − 1.103) in forced expiratory volume in one second /predict (FEV1%pred), a decline of 193 ml/s (95% CI: −258 to − 43) in peak expiratory flow (PEF), a decline of 0.932% (95% CI: −1.518 to − 0.342) in maximal mid-expiratory flow (MMEF); an increase of 0.732 Hz (95% CI: 0.313 to 1.148) in resonant frequency (Fres), an increase of 36 kpa/(ml/s) (95% CI: 14 to 57) in impedance at 5 Hz (Z5) and an increase of 31 kpa/(ml/s) (95% CI: 2 to 54) in respiratory impedance at 5 Hz (R5). Compared to patients in the central district, those in the southern district had lower FEV1/FVC, FEV1%pred, PEF, FEF75%, MMEF, X5, and higher Fres, Z5 and R5 (p < 0.05). Conclusion: Short-term exposure to PM2.5 was associated with reductions in lung function indices and an increase in IOS results in patients with COPD. The heavier the PM2.5, the more severe of COPD. [ABSTRACT FROM AUTHOR]

Introduction: To summarize the clinical experiences with double plasma purification (DPP). Method: Using Plasauto iQ automatic blood purification system, model KM‐9000 for DPP. Results: A total of 603 patients with different entity undergoing 811 purification procedures were included in this study. The most common purification modes were dual filtration plasma plasmapheresis (DFPP). Hyperlipidemia was the lead entity, 423 patients with hyperlipidemia performed DFPP, and two cases of severe acute pancreatitis caused by extremely high triglyceride levels completely recovered after two consecutive DFPP treatments. DFPP combined with immunosuppressants tended to decrease independent HD and reduced HD frequency in 53 patients with antineutrophil cytoplasmic antibody‐associated vasculitis. Two patients developed hypotensive or hypoglycemia episodes, respectively, during purification procedures. Conclusion: DPP is rapid for the treatment of patients with severe hyperlipidemia and acute pancreatitis caused by severely high triglyceride levels. For those who are intolerant to statins，DPP provides another treatment choice. DPP process is safe. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is a chronic, devastating disease primarily occurring in premature infants. To date, intervention strategies to prevent or treat BPD are limited. We aimed to determine the effects of umbilical cord blood‐derived exosomes (UCB‐EXOs) from healthy term pregnancies on hyperoxia‐induced lung injury and to identify potential targets for BPD intervention. A mouse model of hyperoxia‐induced lung injury was created by exposing neonatal mice to hyperoxia after birth until the 14th day post birth. Age‐matched neonatal mice were exposed to normoxia as the control. Hyperoxia‐induced lung injury mice were intraperitoneally injected with UCB‐EXO or vehicle daily for 3 days, starting on day 4 post birth. Human umbilical vein endothelial cells (HUVECs) were insulted with hyperoxia to establish an in vitro model of BPD to investigate angiogenesis dysfunction. Our results showed that UCB‐EXO alleviated lung injuries in hyperoxia‐insulted mice by reducing histopathological grade and collagen contents in the lung tissues. UCB‐EXO also promoted vascular growth and increased miR‐185‐5p levels in the lungs of hyperoxia‐insulted mice. Additionally, we found that UCB‐EXO elevated miR‐185‐5p levels in HUVECs. MiR‐185‐5p overexpression inhibited cell apoptosis, whereas promoted cell migration in HUVECs exposed to hyperoxia. The luciferase reporter assay results revealed that miR‐185‐5p directly targeted cyclin‐dependent kinase 6 (CDK6), which was downregulated in the lungs of hyperoxia‐insulted mice. Together, these data suggest that UCB‐EXO from healthy term pregnancies protect against hyperoxia‐induced lung injuries via promoting neonatal pulmonary angiogenesis partially by elevating miR‐185‐5p. [ABSTRACT FROM AUTHOR]

Two new guaiacene-type sesquiterpenes 13α-dihydroixerin acid, ixerin acid and one new secoguaiacene-type sesquiterpene secoixerin Z, along with four known compounds, were separated from ethanol extract of Ixeris sonchifolia. The structures were determined based on the detailed spectroscopic and physicochemical methods. The cytotoxic activity of the isolates was tested against A549 cells. Among them, compound 3 exhibited potent cytotoxicity against A549 cells with the IC50 of 5.6 ± 0.9 µM. [ABSTRACT FROM AUTHOR]

Polycyclic N-heterocycles are important structural motifs commonly found in bioactive compounds, however, their selective construction via the cyclization of allenynes remains challenging yet highly desirable. Here we show a homogeneous copper-catalyzed hetero Diels−Alder (HDA) reaction of allenynes with cis-diazenes (PTAD, 4-phenyl-1,2,4-triazoline-3,5-dione), allowing the practical and efficient synthesis of a diverse array of valuable polycyclic N-heterocycles. A temperature-controlled and stereocontrolled chemoselectivity of the reaction was observed, leading to the chemodivergent synthesis of tetracyclic pyrrolidines, pentacyclic triazepanes and tricyclic pyrrolidines. Compared with related Au-catalyzed cyclization of allenynes, this copper catalysis achieves cyclization of allenynes terminating in C–N bond formation via the HDA reaction. Polycyclic N-heterocycles are important structural motifs commonly found in bioactive compounds, however, their selective construction via the cyclization of allenynes remains challenging. Here, the authors develop a copper-catalyzed, temperature-controlled regioselective hetero Diels-Alder reaction of allenynes with cis diazenes to produce a diverse array of polycyclic N-heterocycles. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is characterized by abnormal development of the blood vessels and alveoli in lungs, which largely occurs in premature infants. Exosomes (EXO) from very preterm infants (VPI) with BPD (BPD-EXO) impair angiogenic activities of human umbilical vein endothelial cells (HUVECs) via EXO-miRNAs cargo. This study aimed to determine whether and how BPD-EXO affect the development of BPD in a mouse model. We showed that treating BPD mice with BPD-EXO chronically and irreversibly aggravated lung injury. BPD-EXO up-regulated 139 and down-regulated 735 genes in the mouse lung tissue. These differentially expressed genes were enriched to the MAPK pathway (e.g., Fgf9 and Cacna2d3), which is critical to angiogenesis and vascular remodeling. BPD-EXO suppressed expression of Fgf9 and Cacna2d3 in HUVECs and inhibited migration, tube formation, and increased cell apoptosis in HUVECs. These data demonstrate that BPD-EXO aggravate lung injury in BPD mice and impair lung angiogenesis, plausibly leading to adverse outcomes of VPI with BPD. These data also suggest that BPD-EXO could serve as promising targets for predicting and treating BPD. [ABSTRACT FROM AUTHOR]

Introduction: Eleutherococcus senticosus fruit (ESF) is a natural health supplement resource that has been extensively applied as a tonic for the nervous system. The structures and neural bioactivities of triterpenoid saponins (TS), which are the major constituents of ESF, have not been comprehensively analyzed thus far. Objective: We conducted a complete in‐depth MS/MS molecular networking (MN)‐based targeted analysis of TS from the crude extract of ESF and investigated its neuroprotective value. Methods: An MS/MS MN‐guided strategy was used to rapidly present a series of precursor ions (PIs) of TS in a compound cluster as TS‐targeted information used in the discovery and characterization of TS. In addition, a prepared TS‐rich fraction of ESF was assayed for its restraining effects on β‐amyloid‐induced inhibition of neurite outgrowth. Results: A total of 87 TS were discovered using a PI tracking strategy, 28 of which were characterized as potentially undescribed structures according to their high‐resolution MS values. Furthermore, the TS‐rich fraction can significantly reduce β‐amyloid‐induced damage to neural networks by promoting the outgrowth of neurites and axons. Conclusion: Our findings reveal the richness of TS in ESF and will accelerate their application in the treatment of neurodegenerative diseases. Eleutherococcus senticosus fruit (ESF) is a natural health supplement resource that has been extensively applied as a tonic for the nervous system. In this paper, a comprehensive LC‐MS analysis of triterpene saponins (TS) from ESF was performed using an MS/MS molecular networking strategy, and 87 TS were finally tracked, of which 28 TS were potential new saponins. In addition, the TS‐rich fraction of ESF was prepared and assayed for their restraining effect on the β‐amyloid‐induced destruction of neurite outgrowth. [ABSTRACT FROM AUTHOR]

General access to highly valuable seven-membered rings via Büchner-type reaction remains a formidable challenge. Here we report a Cu-catalyzed intermolecular oxidation of alkynes using N-oxides as oxidants, which enables expedient preparation of valuable benzo[6,7]azepino[2,3-b]quinolines and pyridine-based diones. Importantly, in contrast to the well-established gold-catalyzed intermolecular alkyne oxidation, the dissociated pyridine or quinoline partner could be further utilized to construct N-heterocycles in this system and the reaction most likely proceeds by a Büchner-type ring expansion pathway. A mechanistic rationale for this cascade cyclization is supported by DFT calculations. Organic molecules containing seven-membered rings are important structural motifs for drug candidates, but the construction of seven-membered rings can be challenging through traditional cyclization pathways. Here, the authors report a copper-catalyzed alkyne oxidation and Büchner-type ring-expansion to generate benzo[6,7]azepino[2,3-b]quinolines and pyridine-based diones. [ABSTRACT FROM AUTHOR]

Dearomatizing spirocyclization reactions are very appealing synthetic strategies to generate functionalized three-dimensional scaffolds from simple two-dimensional precursors. Recently, the field of transition-metal-catalyzed dearomatizing spirocyclization reactions of indolyl ynones has burgeoned, as the construction of synthetically challenging quaternary spirocyclic carbons is easily achieved. In this review, we introduce an overview of advances in the transition-metal-catalyzed dearomatizing spirocyclization reactions of indolyl ynones, with the reactions being categorized according to type of catalyst. [ABSTRACT FROM AUTHOR]

An efficient copper-catalyzed oxidative cyclization of diynes is described. A range of functionalized γ-lactams can be readily constructed by using this protocol. This copper-catalyzed oxidative process proceeds through an alkyne oxidation, carbene/alkyne metathesis, and donor–donor carbene oxidation sequence. The use of readily available substrates, high flexibility, a simple procedure, and mild reaction conditions render the procedure a viable alternative for the preparation of functionalized γ-lactams. [ABSTRACT FROM AUTHOR]

Background: A variety of autoantibodies have been detected in primary biliary cholangitis (PBC), while the presence of autoantibody clusters and their clinical significance have not been fully understood. We aimed at defining autoantibody clusters and to better understand the clinical features and prognosis of PBC patients based on autoantibody clusters under real-world conditions. Methods: We retrospectively analyzed 788 inpatients with PBC evaluated between October 2008 and July 2019, and included 537 patients. Nineteen autoantibodies which were measured routinely were investigated for cluster analysis. Two-step clustering, Kaplan-Meier survival, and Cox regression analyses were used. Results: Five clusters were defined. A cluster of antinuclear antibodies (ANA) and anti-gp210 positive patients were identified with a high rate of cirrhosis at baseline and low survival rate; a cluster of ANA, anti-centromere antibodies (ACA) and/or anti-CENP-B female dominant patients with older disease onset, low level of platelet count at baseline, high rate of hepatic decompensation, and low survival rate was also characterized; and another cluster of antimitochondrial antibodies (AMA) and/or AMA-M2, anti-Ro52 and a high rate of anti-gp210 positive patients were identified with a high proportion of male patients and low survival rate. A subgroup of patients with anti-SSA and/or anti- SSB coexists with SjS was also identified; patients with only AMA and/or AMAM2- positive with a benign clinical outcome and relatively high complication of non-alcoholic fatty liver disease (NAFLD) were also identified. Only anti-gp210 was considered as a significant predictor for poor outcomes especially in patients with cirrhosis. Conclusion: Clustering methods allow the identification of distinct autoantibody profiles of PBC that form clinical subsets and can be useful for personalized approaches to diagnosis, clinical management, and the prediction of clinical outcomes. Anti-gp210 was the strongest predictive factor for poor outcomes especially in PBC patients with cirrhosis under real-world conditions. [ABSTRACT FROM AUTHOR]

Salicylic acid (SA) is a plant defense hormone required for immunity. Group II TGA transcription factors could interact with NPR1 to positively regulate SA-induced PR gene expression and pathogen resistance. In this study, one group II TGA gene from apple, MdTGA2.1, was functionally characterized detailed. The expression of MdTGA2.1 was mainly expressed in the leaves and up-regulated by SA treatment. MdTGA2.1-GFP fusion protein was observed only in the nucleus in the transient expression assay. Yeast two-hybrid and pull-down assays revealed that MdTGA2.1 could interact with MdNPR1. Overexpression of MdTGA2.1 in the tga6-1tga2-1tga5-1 triple mutant and wild-type Col conferred decreased SA sensitivity, including the SA-mediated seedlings growth inhibition, and the susceptibility to the bacterial pathogen Pst DC3000. In addition, MdTGA2.1 overexpression also improved the tolerance to NaCl and PEG treatments in transgenic Arabidopsis. Taken together, our findings suggest that apple MdTGA2.1 not only involved in the SA responses but also played roles in the stress tolerance. [ABSTRACT FROM AUTHOR]

Lactifluus is a distinct genus of milkcaps, well known as ectomycorrhizal fungi. The characteristics of the genus Lactifluus include grayish-yellow, orange to orange-brown, or reddish-brown pileus, white latex from the damaged lamellae, discoloring to a brownish color, reticulate spore ornamentation, lampropalisade-type pileipellis, and the presence of lamprocystidia. Guizhou Province is rich in wild mushroom resources due to its special geographical location and natural environment. In this study, three novel Lactifluus species were identified through the screening of extensive fungal resources in Suiyang County, Guizhou Province, China, sampled from host species of mostly Castanopsis spp. and Pinus spp. Based on critical morphology coupled with nuclear sequences of genes encoding large subunit rRNA, internal transcribed spacer, and RNA polymerase II, these new species, Lactifluus taibaiensis, Lactifluus qinggangtangensis, and Lactifluus jianbaensis, were found to belong to Lactifluus section Lactifluus. A comparison with closely related species, Lactifluus taibaiensis was distinguished by its lighter-colored pileus, different colors of lamellae, and more subglobose basidiospores; Lactifluus jianbaensis was identified by the height of the spore ornamentation and its subglobose basidiospores; and Lactifluus qinggangtangensis was characterized by having smaller basidiospores, ridges, and pleurolamprocystid. [ABSTRACT FROM AUTHOR]

[Objectives] To determine whether the great spotted woodpecker Dendrocopos major (GSW), an important predator of stem boring pests, can be used as a biological control for the longhorn beetle, Anoplophora glabripennis (ALB), in the Hexi Corridor of Gansu province. [Methods] Control of ALB by the GSW was monitored in 4 different habitats in Suzhou District, Jiuquan City from 2018 to 2021. The rate of decline of the ALB population and the proportion of infested plants were counted, and transects were used to count the number of GSW and GSW peck marks per unit area (6.67 hm²). [Results] The ALB population declined in control plots in all four habitats. In test plots, the proportion of insect-infested plants decreased significantly, and the corrected rate of insect population decline steadily accelerated. There was an upward trend in the number of GSW found per unit area and the number of peck marks in the 4 habitats. Over the past 4 years, the number of peck marks in experimental plots has increased yearly. With the exception of Jiuquan park, the number of peck marks has continued to increase annually. The rate of increase in peck marks in the other three plots peaked in 2018, and has since slowed down. The frequency of GSW per unit area in the West Han Dynasty Jiuquan scenic spot, Wutong garden and Xifeng experimental station is significantly, negatively correlated with the proportion of insect-infested plants. [Conclusion] Introducing the GSW can effectively control ALB and habitat quality appears to be the main factor affecting the success of such biological control. If suitable GSW habitat can be created in the Hexi Corridor, then effective biological control of stem-boring pests such as the ALB is feasible. [ABSTRACT FROM AUTHOR]

Recent studies have found that adults have stronger attentional bias toward neutral infant faces than emotional (positive or negative) infant faces. This phenomenon may derive from uncertainty over neutral expressions. To test this hypothesis, we recruited 176 participants to examine the relationship between their attentional bias toward neutral infant faces (with neutral adult faces as a comparison baseline) and their level of certainty in their appraisal of emotional valence through eye‐tracking indices. The results showed that participants had a longer dwell time and higher fixation counts for infant faces than for adult faces and that a more uncertain appraisal of facial expressions positively predicted attentional bias toward neutral infant faces. Therefore, this study preliminarily demonstrates that emotional uncertainty heightens adults' attentional bias toward infant faces with neutral expressions. [ABSTRACT FROM AUTHOR]

Single cell analysis is crucial for elucidating cellular diversity and heterogeneity as well as for medical diagnostics operating at the ultimate detection limit. Although superbly sensitive biosensors have been developed using the strongly enhanced evanescent fields provided by optical microcavities, real-time quantification of intracellular molecules remains challenging due to the extreme low quantity and limitations of the current techniques. Here, we introduce an active-mode optical microcavity sensing stage with enhanced sensitivity that operates via Förster resonant energy transferring (FRET) mechanism. The mutual effects of optical microcavity and FRET greatly enhances the sensing performance by four orders of magnitude compared to pure Whispering gallery mode (WGM) microcavity sensing system. We demonstrate distinct sensing mechanism of FRET-WGM from pure WGM. Predicted lasing wavelengths of both donor and acceptor by theoretical calculations are in perfect agreement with the experimental data. The proposed sensor enables quantitative molecular analysis at single cell resolution, and real-time monitoring of intracellular molecules over extended periods while maintaining the cell viability. By achieving high sensitivity at single cell level, our approach provides a path toward FRET-enhanced real-time quantitative analysis of intracellular molecules. The authors introduce an active-mode optical microcavity sensor with enhanced sensitivity via Förster resonant energy transfer. Changes in lasing wavelengths of both donor and acceptor enable quantitative molecular analysis and real-time monitoring of intracellular molecules. [ABSTRACT FROM AUTHOR]

Gastric carcinoma (GC) is the fourth most common malignancy worldwide and the second cause of death of all malignancies worldwide. AMPK catalytic subunit a1 (PRKAA1) is involved in various types of cancer and PRKAA1 knockdown significantly decreased the invasiveness of GC cells. Fat mass and obesity-associated protein (FTO)-regulation of m6A has been shown to be involved in different diseases including cancer. However, the role of PRKAA1 and m6A modification in GC remains to be elucidated. PRKAA1 was silenced or overexpressed to study the role of PRKAA1 in regulating cell viability, colony formation, and glycolysis. Levels of lactic acid, GSH, and NADP+/NADPH were measured using commercial kits. Extracellular acidification rates were determined by an extracellular flux analyzer. RNA immunoprecipitation was performed to test m6A levels and the interaction between PRKAA1-3'-UTR and YTHDF2. Quantitative RT-PCR and immunoblots were applied to measure mRNA or protein levels, respectively. PRKAA1 silencing inhibited cell growth, colony formation, and glycolysis but enhanced apoptosis, while the PRKAA1 overexpression promoted cell growth, colony formation, and glycolysis but inhibited apoptosis of GC cells. Data also indicated that PRKAA1 regulated cell growth and apoptosis by regulating the redox balance. Mechanism study demonstrated that FTO regulated PRKAA1 mRNA m6A modification and stability. Clinical samples analysis demonstrated that PRKAA1 and FTO expression were increased in GC patients and positively correlated with each other. FTO increased levels of PRKAA1 by regulating its mRNA m6A modification and stability. PRKAA1, in turn, promoted cell viability, colony formation, and glycolysis but inhibited apoptosis of GC cells by promoting the redox balance. [ABSTRACT FROM AUTHOR]

Background: Laryngeal cancer (LC) is a prevalent head and neck malignancy; however, the essential pathophysiological mechanism underlying its tumorigenesis and progression remains elusive. Due to the perduring scarcity of effective targeted drugs for laryngeal cancer, insights into the disease’s pathophysiological mechanisms would substantially impact the treatment landscape of laryngeal cancer. Methods: To ensure quality consistency, 10 tumor and 9 non-tumor samples underwent proteomic analysis on a single mass spectrometer using a label-free technique. Subsequently, gene expression variations between laryngeal squamous cell carcinoma and normal tissues were analyzed using The Cancer Genome Atlas (TCGA) database. Immunohistochemical expressions of insulinlike growth factor 2 receptor (IGF2R), fibronectin (FN), vimentin, and a-smooth muscle actin (SMA) in LC tissues and normal tissues were determined. Results: In the tumor group, significant variations were detected for 433 upregulated and 61 downregulated proteins. Moreover, the heatmap revealed that the expressions of RNA translation-related proteins and proteins involved in RNA metabolism, such as IGF2R, tenascin C (TNC), periostin (POSTN), proteasome 26S subunit ATPase 4 (PSMC4), serpin family A member 3 (SERPINA3), heat shock protein family B (small) member 6 (HSPB6), osteoglycin (OGN), chaperonin containing TCP1 subunit 6A (CCT6A), and chaperonin containing TCP1 subunit 6B (CCT6B), were prominently elevated in the tumor group. Nonsense-mediated RNA decay (NMD), RNA translation, and protein stability were significantly altered in LC tumors. IGF2R was remarkably upregulated in LC tumors. In the TCGA database, the IGF2R mRNA level was significantly upregulated in LSCC tissues. Additionally, IGF2R mRNA expression was lowest in clinical grade 1 samples, with no significant difference between grades 2 and 3. In LSCC patients, a significant positive correlation between IGF2R expression and the stromal score was detected using the ESTIMATE algorithm to estimate the immune score, stromal score, and tumor purity in the tumor microenvironment. Lastly, immunohistochemical analysis revealed that IGF2R is overexpressed in LC. Conclusion: These results demonstrate the vital role of IGF2R in LC carcinogenesis and progression and may facilitate the identification of new therapeutic targets for the prevention and treatment of LC. [ABSTRACT FROM AUTHOR]

To explore compliance with oral nutritional supplementation (ONS) and to identify the risk factors for noncompliance among gastric cancer patients based on the health belief model (HBM) This prospective, observational study included gastric cancer patients at nutritional risk who were prescribed ONS from July to September 2020. Demographic factors, clinical factors, ONS-related factors, social factors and variables derived from the HBM were collected. The outcome of interest was compliance with ONS, which was measured by self-reported intake of ONS. Uni- and multivariate analyses of potential risk factors for noncompliance were performed. A total of 162 gastric cancer patients in the preoperative and adjuvant chemotherapy periods were analyzed. The compliance rate with ONS was 24.7%. Univariate analysis identified thirteen variables as risk factors for decreased compliance. Multivariate logistic analysis indicated that ONS compliance was independently associated with the treatment period, perceived barriers to ONS, the motivation to take ONS, and the timing of taking ONS. This study showed that overall ONS compliance among gastric cancer patients was notably low. Patients in the chemotherapy treatment period who took ONS at random times each day perceived more barriers to taking ONS and had a lower level of motivation were associated with lower compliance with ONS. [ABSTRACT FROM AUTHOR]

Background: The human leukocyte antigen (HLA) susceptibility gene is the main genetic risk factor for primary biliary cholangitis (PBC). The prognosis of patients with PBC is linked to gut microbiota dysbiosis. However, whether the HLA alleles are associated with the gut microbiota distribution and disease severity remains unknown. Methods: A cohort of 964 Chinese patients with PBC was enrolled at Beijing YouAn Hospital, Beijing, China. High-resolution genotyping of the HLA class I and class II loci from 151 of these patients was performed using sequence-based PCR. Stool samples were collected from43 of the 151 fully HLA-typed patients to analyze their microbiota compositions via 16S RNA gene sequencing. Results: Of the 964 patients, the male:female ratio was 114:850, and 342 of these patients (35.5%) had already developed liver cirrhosis (LC) before enrollment. Patients with PBC showed a significantly higher frequency of HLA DRB1*08:03 than did the controls (21.2% vs. 9.0%, P=0.0001). HLA-DRB1*03:01, DRB1*07:01, DRB1*14:05, and DRB1*14:54 frequencies were also increased but did not reach significance after Bonferroni's correction. Conversely, the DQB1*03:01 frequency was significantly lower in patients with PBC than in the controls (24.5% vs. 39.2%, P=0.0010). The patients' gutmicrobiotawere analyzed from four perspectives. The microbial community abundances were significantly lower in FHRAC-positive patients (patients with a combination of five HLA DRB1 high-risk alleles) than in FHRAC-negative patients (P<0.05). Of the top 10 microbial genera, Lachnospiraceae_incertae_sedis was higher in the FHRACpositive patients than in the FHRAC-negative patients (P<0.05). linear discriminant analysis (LDA) effect-size (LEfSe) analysis showed different microbes at different levels in the FHRAC-negative patients but not in the FHRAC-positive patients. DQB1*03:01-positive patients contained mostly Lactobacillaceae at the family level. A comparison of the FHRAC-positive patients with and without liver cirrhosis showed that the abundances of Veillonella were significantly higher in patients with cirrhosis and FHRAC than in those without cirrhosis and are FHRAC-negative. Conclusion: The HLA class II genes may influence the gut microbiota compositions in patients with PBC. Differential gut microbiota were expressed at different taxonomic levels. Some bacterial abundances may be increased in FHRAC-positive patients with PBC and cirrhosis. [ABSTRACT FROM AUTHOR]

This study aims to validate the simplified Chinese version of the Social Communication Questionnaire (SCQ) in children aged 2–12 years from both general and clinical populations. We recruited 819 Chinese children in this study, including 505 typically developing (TD) children, 202 children with autism spectrum disorder (ASD) and 112 children with non‐ASD neurodevelopmental disorders. All the children's parents completed the simplified Chinese version of the SCQ and all children with ASD were additionally assessed for intelligence and the Childhood Autism Rating Scale to confirm their diagnosis. We have developed a 40‐item, 4‐factor structure of SCQ with two domains (social communication and social interaction; and restricted, repetitive, and stereotyped patterns of behavior), which showed adequate goodness of fit (comparative fit index [CFI] = 0.96, Tucker‐Lewis index [TLI] = 0.95, standardized root mean squared residual [SRMR] = 0.07, root mean square error of approximation [RMSEA] = 0.05), with good internal consistency (Cronbach's alpha = 0.92). We have provided different cut‐offs to distinguish ASD cases from TD children (11 for children under 4 years [sensitivity: 0.96, specificity: 0.95], 12 for children 4 years and above [sensitivity: 0.93, specificity: 0.98]) or children with other neurodevelopmental disorders (14 [sensitivity: 0.85, specificity: 0.88]). Through this large sample validation, we confirmed that the simplified Chinese version of the SCQ could be used for children aged 2–12 years with relatively good psychometric properties. Lay Summary: We aimed to develop the simplified Chinese version of the Social Communication Questionnaire (SCQ) for Chinese children aged 2–12 years as a screening tool to identified potential risk of autism spectrum disorder (ASD). We have developed a 40‐item, 4‐factor structure of SCQ with two domains, which showed adequate goodness of fit and good psychometric properties. We also provided different cut‐offs to identify ASD cases in general or clinical populations. [ABSTRACT FROM AUTHOR]