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Background: Accelerated biological aging has been verified to be a critical risk factor for a number of age-related diseases, but its role in dementia remained unclear. Whether it modified the effects of genetic factors was also unknown. This study evaluated the associations between accelerated biological aging and dementia and the moderating role of accelerated biological aging in the genetic susceptibility to the disease. Methods: We included 200,731 participants in the UK biobank. Nine clinical blood biomarkers and chronological age were used to calculate Phenotypic age acceleration (PhenoAgeAccel), which is a novel indicator for accelerated biological aging. The associations of PhenoAgeAccel with dementia, both young-onset and late-onset dementia, were assessed by Cox proportional hazard models. Apolipoprotein E (APOE) alleles and polygenic risk scores (PRS) were used to evaluate the genetic risk of dementia. The interactions between genetic susceptibility and biological aging were tested on both multiplicative and additive scales. Results: These findings showed individuals who were in the highest quartile of PhenoAgeAccel had a higher risk with incidence of dementia compared to individuals in the lowest quartile of PhenoAgeAccel (HR: 1.145 (95% CI: 1.050, 1.249)). Individuals with biologically older had a higher risk of dementia than individuals with biologically younger (HR: 1.069 (95% CI: 1.004, 1.138)). Furthermore, compared to individuals with biologically younger and low APOE ε4-related genetic risk, individuals with biologically younger and high APOE ε4-related genetic risk (HR:3.048 (95% CI: 2.811, 3.305)) had a higher risk of dementia than individuals with biologically older and high APOE ε4-related genetic risk (HR: 2.765 (95% CI: 2.523, 3.029)). Meanwhile, referring to low dementia PRS and biologically younger, the risk of dementia increased by 72.7% (HR: 1.727 (95% CI: 1.538, 1.939) in the biologically younger and high PRS group and 58.7% (HR: 1.587 (95% CI: 1.404, 1.793) in the biologically older and high PRS group, respectively. The negative interactions between PhenoAgeAccel with APOE ε4 and PRS were also tested on the additive scale. Conclusions: Accelerated biological aging could bring the extra risk of dementia but attenuate the effects of genetic risk on dementia. These findings provide insights for precise prevention and intervention of dementia. [ABSTRACT FROM AUTHOR]

Aim: The relationship between the gut microbiota, metabolites and body fat percentage (BFP) remains unexplored. We systematically assessed the causal relationships between gut microbiota, metabolites and BFP using Mendelian randomization analysis. Materials and Methods: Single nucleotide polymorphisms associated with gut microbiota, blood metabolites and BFP were screened via a genome‐wide association study enrolling individuals of European descent. Summary data from genome‐wide association studies were extracted from the MiBioGen consortium and the UK Biobank. The inverse variance‐weighted model was the primary method used to estimate these causal relationships. Sensitivity analyses were performed using pleiotropy, Mendelian randomization‐Egger regression, heterogeneity tests and leave‐one‐out tests. Results: In the aspect of phyla, classes, orders, families and genera, we observed that o_Bifidobacteriales [β = −0.05; 95% confidence interval (CI): −0.07 to −0.03; false discovery rate (FDR) = 2.76 × 10−3], f_Bifidobacteriaceae (β = −0.05; 95% CI: −0.07 to −0.07; FDR = 2.76 × 10−3), p_Actinobacteria (β = −0.06; 95% CI: −0.09 to −0.03; FDR = 6.36 × 10−3), c_Actinobacteria (β = −0.05; 95% CI: −0.08 to −0.02; FDR = 1.06 × 10−2), g_Bifidobacterium (β = −0.05; 95% CI: −0.07 to −0.02; FDR = 1.85 × 10−2), g_Ruminiclostridium9 (β = −0.03; 95% CI: −0.06 to −0.01; FDR = 4.81 × 10−2) were negatively associated with BFP. G_Olsenella (β = 0.02; 95% CI: 0.01‐0.03; FDR = 2.16 × 10−2) was positively associated with BFP. Among the gut microbiotas, f_Bifidobacteriales, o_Bifidobacteriales, c_Actinobacteria and p_Actinobacteria were shown to be significantly associated with BFP in the validated dataset. In the aspect of metabolites, we only observed that valine (β = 0.77; 95% CI: 0.5‐1.04; FDR = 8.65 × 10−6) was associated with BFP. Conclusions: Multiple gut microbiota and metabolites were strongly associated with an increased BFP. Further studies are required to elucidate the mechanisms underlying this putative causality. In addition, BFP, a key indicator of obesity, suggests that obesity‐related interventions can be developed from gut microbiota and metabolite perspectives. [ABSTRACT FROM AUTHOR]

Introduction: Prodromal Parkinson's disease (PD) carriers of dual leucine‐rich repeat kinase 2 (LRRK2) and glucosylceramidase β (GBA) variants are rare, and their biomarkers are less well developed. Objective: This study aimed to investigate the biomarkers for diagnosing the prodromal phase of LRRK2‐GBA‐PD (LRRK2‐GBA‐prodromal). Methods: We assessed the clinical and whole‐brain white matter microstructural characteristics of 54 prodromal PD carriers of dual LRRK2 (100% M239T) and GBA (95% N409S) variants, along with 76 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort. Results: By analyzing the four values of 100 nodes on 20 fiber bundles, totaling 8000 data points, we identified the smallest p value in the fractional anisotropy (FA) value of the 38th segment of left corticospinal tract (L‐CST) with differences between LRRK2‐GBA‐prodromal and HCs (p = 8.94 × 10−9). The FA value of the 38th node of the L‐CST was significantly lower in LRRK2‐GBA‐prodromal (FA value, 0.65) compared with HCs (FA value, 0.71). The receiver‐operating characteristic curve showed a cut‐off value of 0.218 for the FA value of L‐CST, providing sufficient sensitivity (79.2%) and specificity (72.2%) to distinguish double mutation prodromal PD from the healthy population. Conclusion: L‐CST, especially the 38th node, may potentially serve as a biomarker for distinguishing individuals with double mutation prodromal PD from the healthy population. [ABSTRACT FROM AUTHOR]

Introduction: The emergence of multidrug-resistant Klebsiella pneumoniae (K. pneumoniae) and the decline of effective antibiotics lead to the urgent need for new antibacterial agents. The aim of this study is to investigate the therapeutic effect of antimicrobial peptides against gentamicin-resistant (RT) K. pneumoniae and to screen effective antimicrobial peptides. Methods: In this study, the RT strains were induced by gradient gentamicin, and the RT strains were selected by detecting the expression levels of efflux pump genes, porin genes, and biofilm formation genes of the strains combined with their effects on the cells. Then the effects of four antimicrobial peptides on the efflux pump activity, biofilm formation level and cell condition after infection were detected to explore the effects of antimicrobial peptides on RT strains. Finally, the RT strain was used to induce a mouse model of pneumonia, and the four antimicrobial peptides were used to treat pneumonia mice for in vivo experiments. The pathological changes in lung tissues in each group were detected to explore the antimicrobial peptide with the most significant effect on the RT strain in vivo. Results: The results showed that the minimal inhibitory concentrations of the RT strains (strain C and strain I) were significantly higher than those of the wild-type strain, and the expression of efflux pump, porin and biofilm formation genes was significantly increased. The antimicrobial peptides could effectively inhibit the biofilm formation and efflux pump protein function of the RT strains. In addition, the antimicrobial peptides showed promising antibacterial effects both in vitro and in vivo. Discussion: Our study provided a theoretical basis for the treatment of gentamicin resistant K. pneumoniae infection with antimicrobial peptides, and found that KLA was significantly superior to LL37, Magainin I, KLA and Dermaseptin (10 μg/mL in cells, 50 μg in mice). [ABSTRACT FROM AUTHOR]

Increasing evidence suggests an association between exercise duration and Parkinson's disease. However, no high-quality prospective evidence exists confirming whether differences exist between the two modes of exercise, weekend warrior and equal distribution of exercise duration, and Parkinson's risk. Hence, this study aimed to explore the association between different exercise patterns and Parkinson's risk using exercise data from the UK Biobank. The study analyzed data from 89,400 UK Biobank participants without Parkinson's disease. Exercise data were collected using the Axivity AX3 wrist-worn triaxial accelerometer. Participants were categorized into three groups: inactive, regularly active, and engaged in the weekend warrior (WW) pattern. The relationship between these exercise patterns and Parkinson's risk was assessed using a multifactorial Cox model. During a mean follow-up of 12.32 years, 329 individuals developed Parkinson's disease. In a multifactorial Cox model, using the World Health Organization–recommended threshold of 150 min of moderate-to-vigorous physical activity per week, both the active WW group [hazard ratio (HR) = 0.58; 95% confidence interval (CI) = 0.43–0.78; P < 0.001] and the active regular group (HR = 0.44; 95% CI = 0.34–0.57; P < 0.001) exhibited a lower risk of developing Parkinson's disease compared with the inactive group. Further, no statistically significant difference was observed between the active WW and the active regular groups (HR = 0.77; 95% CI = 0.56–1.05; P = 0.099). In conclusion, in this cohort study, both the WW exercise pattern and an equal distribution of exercise hours were equally effective in reducing Parkinson's risk. [ABSTRACT FROM AUTHOR]

Helianthus annuus seed byproduct is a residual product obtained after seed oil extraction. The present study investigated the preventive and repair effects of the H. annuus seed byproduct ethanol extract (HSE) on ultraviolet radiation (UVR)‐induced injury in human immortalized keratinocytes (HaCaTs) and human skin fibroblasts (HSFs). Results revealed that the total phenolic acid and oligosaccharide content in HSE was >50%. HSE had a stronger preventive effect on UVR‐induced injury than the repair effect. Moreover, phenolic acids were the main active component of HSE mediating the preventative effect. In HaCaTs and HSFs, HSE prevented UVR‐induced injury by inhibiting excessive ROS production. It reduced the secretion of tumor necrosis TNF‐α, IL‐1α, IL‐1β, IL‐6, and IL‐8 by inhibiting the level of ROS, thus reducing inflammation‐mediated injury to skin cells. In addition, HSE inhibited the expression of various mRNA kinases in the MAPK–ERK/p38/JNK pathway. This downregulated the expression of activator protein‐1 (AP‐1) mRNA and further reduced the secretion of matrix metalloproteinase (MMP)‐1, MMP‐3, and MMP‐9 as well as reduced UVR‐induced injury to the cells. In conclusion, HSE is a broad‐spectrum, natural UV filter with high efficiency and low toxicity that has the potential to be used in sunscreen products. [ABSTRACT FROM AUTHOR]

The existing reservoir in the Yongjin block exhibits an extremely low matrix permeability, posing challenges in precisely evaluating the damage caused by fracturing fluid using traditional core flow experimental methods. Currently, there is no established quantitative method for characterizing the degree of damage. In this study, we integrated online nuclear magnetic resonance, microscopic computed tomography, and core displacement experimental techniques, pioneering a novel approach to evaluate damage in deep tight oil reservoirs subjected to hydraulic fracturing. We analyzed the influence patterns of key factors such as backflow pressure differential, shut-in time, invasion volume, and residual retention on rock matrix damage in the operational area. The study unveiled the mechanisms behind water sensitivity, water block, and fracturing fluid retention damage among oil, water, and rock. The results indicate that water sensitivity damage is less than 20%, primarily occurring within large pores. Water block damage can significantly reduce the residual oil permeability. Experimental findings suggest that optimizing liquid backflow with a pressure differential and well shut-in time set at 5 MPa and 9 days can markedly reduce the intrusion volume of gel-breaking fluid, restoring the residual oil permeability. Under high-pressure differential conditions, residual fracturing fluid can infiltrate the rock matrix, resulting in pore damage. Additionally, it can accumulate on the fracture surfaces, thereby reducing the permeability of microfractures. [ABSTRACT FROM AUTHOR]

With a series of redevelopment activities, such as land consolidation and urban renewal, many cities in China have experienced land de-urbanization phenomena. These include the conversion of construction land into green spaces (such as parks, forests, and lawns), blue spaces (such as rivers, lakes, and wetlands), and farmland. However, there is currently limited research on diverse land de-urbanization types and pathways. This study focuses on investigating the land de-urbanization in the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) from 2014 to September 2023 using the Continuous Change Detection and Classification (CCDC) method. The results demonstrate that the GBA experienced 72.74 square kilometers of de-urbanization during the study period, primarily through the conversion of construction land to land with low plant coverage, including grassland and farmland. There were significant differences in the quantity and spatial agglomeration of de-urbanization between cities and within individual cities. Temporally, de-urbanization predominantly occurred in the period of 2016 to 2021, with a sharp decline in 2022. The temporal changes were significantly influenced by urban renewal policies and the impact of the COVID-19 pandemic. In terms of spatial clustering characteristics, the de-urbanization process in the GBA exhibited spatial agglomeration but was primarily characterized by low-level clustering. This study also examines the correlations between de-urbanization and factors including location and the stage of urbanization. The analysis showed that de-urbanization within cities tended to concentrate near the main urban roads within a range of 10–30 km from city centers. The trend of de-urbanization followed a pattern that is consistent with the Northam curve, where de-urbanization tends to increase during the rapid urbanization phase and decline as urbanization reaches a mature stage. Overall, this study provides valuable insights for the redevelopment of construction land within the context of ecological civilization construction. It also offers suggestions for urban land development and redevelopment in metropolitan areas. [ABSTRACT FROM AUTHOR]

Simple Summary: In poultry feed, the oxidative rancidity of lipids is an important factor that affects the quality of feed and the safety of poultry products. Therefore, it is very important to choose and apply antioxidant substances. Tert-butylhydroquinone (TBHQ) is a new and highly effective antioxidant for feeds. However, there is limited information about the effects of TBHQ on animals or poultry in vivo. Moreover, tea polyphenols (TP) are a natural antioxidant that can prevent and treat diseases by scavenging free radicals and regulating the activity of different types of oxidases in the body. This study comprehensively evaluated the effects of a complex antioxidant, the main components of which are TBHQ and TP, on growth performance, meat quality, and antioxidant capacity in broilers. The obtained results revealed that supplementing diets with optimal amounts of TBHQ and TP contributed to serum and liver antioxidant capacity, thereby improving the growth performance and meat quality of broilers. This study aimed to evaluate the effects of diets supplemented with various levels of complex antioxidants (CA) containing tertiary butylhydroquinone (TBHQ) and tea polyphenols (TP) on growth performance, meat quality of breast and leg muscles, serum biochemistry, and antioxidant capacity of serum, liver, breast meat, jejunum, and ileum in broilers. A total of 600 one-day-old Arbor Acres male broilers with similar body weights were randomly divided into three groups (10 replicates/group, 20 broilers/replicate). Birds in the three experimental groups were fed a basal diet with CA at 0, 300, and 500 mg/kg. The results showed that supplementing with 300 mg/kg CA significantly increased (p < 0.05) 42 d BW and 22–42 d ADG, and markedly decreased (p < 0.05) 22–42 d F: G ratio in comparison to the control group. Birds fed a diet with 300 mg/kg CA had a higher (p < 0.05) pH of chicken meat at 24 h and 48 h post mortem and lower (p < 0.05) yellowness values (b*) of chicken meat at 45 min and 24 h post mortem, along with a lower (p < 0.05) cooking loss. Supplementing with 300 mg/kg CA significantly increased (p < 0.05) serum and liver T-SOD activity, serum T-AOC level, as well as jejunual GST activity, and significantly decreased (p < 0.05) liver MDA content when compared with the control group. These results indicate that diet supplementation with 300 mg/kg CA containing TBHQ and TP could improve growth performance and meat quality by increasing the antioxidant capacity of broilers. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the effects of breast milk feeding volume on the early behavioral neurodevelopment of extremely preterm infants (gestational age < 28 weeks). Methods: The study was conducted from 1 January 2021 to 31 March 2023. A total of 187 preterm infants from a neonatal intensive care unit (NICU) in a Grade III Class A hospital in Zhejiang, China, were divided based on the proportion of breast milk in their total enteral nutrition: high proportion (≥ 80%, including exclusive breast milk feeding), medium proportion (20% ~ < 80%), and low proportion (< 20%). The study investigated motor performance and behavioral neurodevelopment at 37 weeks of corrected gestational age, as well as the total incidence of intracranial hemorrhage within the first four weeks postpartum. Results: The low breast milk feeding group had significantly lower scores in infant motor performance (31.34 ± 5.85) and elicited item scores (19.89 ± 5.55) compared to the medium and high groups (33.52 ± 4.33, 22.13 ± 4.22; and 35.86 ± 5.27, 23.91 ± 4.98), p < 0.05, respectively. Despite no significant difference in behavioral ability, the low proportion group exhibited lower passive muscle tension and primitive reflex scores than the medium and high proportion groups. The high proportion group showed higher active muscle tension scores. Ultrasound results revealed varying incidences of intracranial hemorrhage: 72.9% in low, 52.5% in medium, and 19.6% in the high proportion groups. Conclusions: Medium to high levels of breast milk feeding contribute positively to motor and behavioral neurological development in extremely preterm infants and decrease the likelihood of ventricular hemorrhage. However, it does not have a significant effect on the development of behavioral abilities. Due to the limited sample size, the next step will be to expand the sample size and further investigate the extent of the impact on various aspects of the nervous system. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate dietary chitosan oligosaccharides (COS) supplementation on meat quality, chemical composition and oxidative stability in frizzled chickens. A total of 360 one-day-old female frizzled chickens with an average body weight of 34.38 ± 1.23 g were randomly allocated to four groups with six replications (10 chickens/replication) in this 84-day experiment. The chickens in the control group (CON) fed the basal diet and the other three experimental diets were based on the basal diet with 300, 600 and 900 mg/kg COS supplementation, respectively. The results indicated that dietary COS increased growth performance, eviscerated and breast muscle yield while decreased abdominal fat yield, accompanied with increasing pH45min, pH24h, Lightness, drip loss and cooking loss in breast and thigh muscle. The scavenging activity of 2,2-diphenyl-1-picrylhydrazyl, superoxide radical, hydroxyl radical and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt, the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in breast and thigh muscle were improved by COS while malondialdehyde content was decreased. COS up-regulated the gene expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, SOD, CAT and GSH-Px in breast and thigh muscle. In conclusion, dietary COS supplementation improved meat quality by improving pH, colour, water holding capacity and anti-oxidant capacity, accompanied with decreased lipid metabolism in frizzled chickens. Dietary 600 mg/kg COS was recommended in frizzled chickens' diet to improve meat quality. COS improves growth performance of frizzled chickens. COS improves meat quality of frizzled chickens. COS enhances anti-oxidant capacity of frizzled chickens' meat. [ABSTRACT FROM AUTHOR]

Mammalian DNA derived from invertebrates (iDNA), including blowfly iDNA, is an alternative tool to conventional camera trapping in assessing mammalian diversity. The method has been used in tropical mammal surveillance but no attempt has been made to compare the efficacy of blowfly iDNA and camera trapping for monitoring mammal diversity in subtropical forests. We compared the blowfly iDNA monitoring with camera trapping to assess mammal diversity in the subtropical Jiulongfeng Nature Reserve (JLF), China, over a one-month period. The camera traps captured 2508 animal photos of 11 species belonging to four orders, eight genera, and eight families, whereas the blowfly iDNA method successfully detected ten species from six orders, eight genera, and eight families in JLF. Both methods were complementing each other instead of competing due to the low overlaps of mammal species detected. Of the total number of mammal species listed in JLF's threatened list, 40% and 10% were detected through camera traps and blowfly iDNA methods, respectively. The estimated species richness curves indicated that combining camera traps and blowfly traps would increase the detection of mammal species. The strategy would significantly contribute to mammalian diversity surveillance and conservation programs in the tropical and subtropical forests. [ABSTRACT FROM AUTHOR]

Although aging and apolipoprotein E (APOE) ε4 allele have been documented as two major risk factors for late‐onset Alzheimer's disease (LOAD), their interaction and potential underlying mechanisms remain unelucidated. Using humanized ApoE4‐ and ApoE3‐ target replacement mice, we found the accumulation of senescent neurons and the activation of mTOR and endosome‐lysosome‐autophagy (ELA) system in the hippocampus of aged ApoE4 mice. Further analyses revealed that ApoE4 aggravated the profile change of hippocampal transcription and metabolism in an age‐dependent manner, accompanying with an disruption of metabolism, which is presented with the downregulating activity of citrate synthase, the level of ATP and, most importantly, the level of acetyl coenzyme A (Ac‐CoA); GTA supplement, an Ac‐CoA substrate, reversed the senescent characteristics, decreased the activation of mTOR and ELA system, and enhanced the synaptic structure and increasing level of pre‐/post‐synaptic plasticity‐related protein, leading to cognitive improvement in aged ApoE4 mice. These data suggest that ApoE4 exacerbates neuronal senescence due to a deficiency of acetyl‐CoA, which can be ameliorated by GTA supplement. The findings provide novel insights into the potential therapeutic value of GTA supplement for the cognitive improvement in aged APOE4 carriers. [ABSTRACT FROM AUTHOR]

Introduction: Gonadotropin-releasing hormone (GnRH) is a hypothalamic neuropeptide that plays important roles in the female fertility. Accumulating evidence suggests that ERα present in the astrocytes of the hypothalamus region is essential for production of GnRH. The astrocytes display age-related senescence associated to oxidative stress induced by the estrogen metabolites. However, it is still unclear whether and how ERα expression changes during astrocyte aging. Methods: Immunofluorescence was performed to analyze the ERα gene levels in hypothalamic astrocytes of naturally aging C57BL/6J female mice. We employed an oxidative stress cell model receiving 2-hydroxyestradiol (2OH-E2) intervention to confirm the downregulation of ERα expression in primary astrocytes. Western blot analysis was used to explore which oxidative stress signaling pathways induced loss of the ERα gene. Finally, ChIP-qPCR was employed to evaluate whether the c-Jun protein is able to regulate ERα gene expression. Results: Compared to young mice, we found that the ERα expression of mid-aged mice was significantly decreased. In hypothalamic astrocytes, 2OH-E2 treatment significantly reduced the expression of the ERα gene. Moreover, we observed that transcription factor c-Jun could directly inhibit transcriptional ERα gene expression and might also reduce it by decreasing H3K27 acetylation at promoter regions. Administration of the antioxidants Rg1 and astaxanthin significantly attenuated the decrease in ERα gene expression induced by oxidative stress. Conclusions: The current data demonstrate that oxidative stress leads to loss of ERα involving the activation of the p38 and ERK1/2 pathways and the induction of the c-Jun protein in hypothalamic astrocytes. C-Jun protein regulates ERα gene expression via direct transcriptional repression or involving histone acetylation modifications at ERα gene promoter sites. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence suggests an association between pro-inflammatory diets and cognitive function. However, only a few studies based on small sample sizes have explored the association between pro-inflammatory diets and dementia using the dietary inflammatory index (DII). Additionally, the relationship between DII and different subtypes of dementia, such as Alzheimer's dementia and vascular dementia, remains largely unexplored. Given the changes in brain structure already observed in patients with dementia, we also investigated the association between DII and magnetic resonance imaging (MRI) measures of brain structure to provide some hints to elucidate the potential mechanisms between pro-inflammatory diet and cognitive decline. Methods: A total of 166,377 UK Biobank participants without dementia at baseline were analyzed. DII calculations were based on the information collected by the 24-h recall questionnaire. Brain structural anatomy and tissue-specific volumes were measured using brain MRI. Cox proportional hazards models, competing risk models, and restricted cubic spline were applied to assess the longitudinal associations. The generalized linear model was used to assess the association between DII and MRI measurements. Results: During a median follow-up time of 9.46 years, a total of 1372 participants developed dementia. The incidence of all-cause dementia increased by 4.6% for each additional unit of DII [hazard ratio (HR): 1.046]. Besides, DII displayed a "J-shaped" non-linear association with Alzheimer's dementia (Pnonlinear = 0.003). When DII was above 1.30, an increase in DII was significantly associated with an increased risk of Alzheimer's dementia (HR: 1.391, 95%CI: 1.085–1.784, P = 0.009). For brain MRI, the total volume of white matter hyperintensities increased with an increase in DII, whereas the volume of gray matter in the hippocampus decreased. Conclusions: In this cohort study, higher DII was associated with a higher risk of all-cause dementia and Alzheimer's dementia. However, our findings suggested that the association with DII and vascular and frontotemporal dementia was not significant. [ABSTRACT FROM AUTHOR]

Background: Nuclear acetyl-CoA pools govern histone acetylation that controls synaptic plasticity and contributes to cognitive deterioration in patients with Alzheimer's disease (AD). Nuclear acetyl-CoA pools are generated partially from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). However, the underlying mechanism of histone acetylation dysregulation in AD remains poorly understood. Methods: We detected ACSS2 expression and histone acetylation levels in the brains of AD patients and 5 × FAD mice. When we altered ACSS2 expression by injecting adeno-associated virus into the dorsal hippocampus of 5 × FAD mice and replenished ACSS2 substrate (acetate), we observed changes in cognitive function by Morris water maze. We next performed RNA-seq, ChIP-qPCR, and electrophysiology to study molecular mechanism underlying ACSS2-mediated spatial learning and memory in 5 × FAD mice. Results: We reported that ACSS2 expression and histone acetylation (H3K9, H4K12) were reduced in the hippocampus and prefrontal cortex of 5 × FAD mice. Reduced ACSS2 levels were also observed in the temporal cortex of AD patients. 5 × FAD mice exhibited a low enrichment of acetylated histones on the promoters of NMDARs and AMPARs, together with impaired basal and activity-dependent synaptic plasticity, all of which were rescued by ACSS2 upregulation. Moreover, acetate replenishment enhanced ac-H3K9 and ac-H4K12 in 5 × FAD mice, leading to an increase of NMDARs and AMPARs and a restoration of synaptic plasticity and cognitive function in an ACSS2-dependent manner. Conclusion: ACSS2 is a key molecular switch of cognitive impairment and that targeting ACSS2 or acetate administration may serve as a novel therapeutic strategy for the treatment of intermediate or advanced AD. Nuclear acetyl-CoA pools are generated partly from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). Model depicts that ACSS2 expression is downregulated in the brains of 5×FAD model mice and AD patients. Of note, ACSS2 downregulation mediates a reduction in ionotropic glutamate receptor expression through histone acetylation, which exacerbates synaptic plasticity impairment in AD. These deficits can be rescued by ACSS2 upregulation or acetate supplementation (GTA, an FDA-approved food additive), which may serve as a promising therapeutic strategy for AD treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: With the demand for high-quality poultry products, it is imperative to exploit effective and green feed additives that can stimulate the latent productive capacity of broiler chickens. Numerous studies have shown that essential oils (EOs) are able to maintain intestinal microflora stabilization, improve the digestion and absorption efficiency of intestine, and have effective anti-inflammatory and antioxidant properties. However, essential oils themselves have many limitations, for example, poor stability and palatability. In this study, we evaluated thymol and carvacrol eutectic (TCE), which was produced using pharmaceutical cocrystal technology in broilers' feed. The results showed that supplementation with TCE in broiler diets can improve growth performance, jejunal morphology, and nutrient absorption and transport capacities, as well as ileal morphology, barrier function, and inflammatory status, which indicates that the bioactive compounds of essential oils treated using pharmaceutical cocrystal technology can play an active role in poultry production. This study aimed to evaluate the effect of diets supplementing with various levels of thymol and carvacrol eutectic (TCE) on growth performance, serum biochemical parameters, intestinal morphology, and the expression of intestinal nutrient absorption, barrier function- and inflammation-related genes in broiler chickens. A total of 640 one-day-old Arbor Acres male broilers with similar body weights were randomly divided into four groups (8 replicates/group, 20 broilers/replicate). Birds in the four experimental groups were fed a basal diet with TCE at 0, 30, 60, or 120 mg/kg. The results showed that the growth performance of birds during 22–42 d or 1–42 d, serum IgE and IgG content at 21 d of age, jejunal and ileal morphology, ileal MUC2, OCLN, and IL-10 mRNA expression were significantly increased compared with the control group (p < 0.05), and the ileal IL-6 mRNA expression quadratically decreased (p < 0.05) with increasing dietary TCE supplemented dosage, and its expression showed a linear downward trend (0.05 < p < 0.1). Meanwhile, compared with the other three groups, birds fed diets with 30 mg/kg TCE presented better (p < 0.05) growth performance, intestinal morphology, and function. These results indicated that the optimal supplementation amount of TCE in the broiler diets was 30 mg/kg. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second cause of the neurodegenerative disorder, affecting over 6 million people worldwide. The World Health Organization estimated that population aging will cause global PD prevalence to double in the coming 30 years. Optimal management of PD shall start at diagnosis and requires both a timely and accurate method. Conventional PD diagnosis needs observations and clinical signs assessment, which are time‐consuming and low‐throughput. A lack of body fluid diagnostic biomarkers for PD has been a significant challenge, although substantial progress has been made in genetic and imaging marker development. Herein, a platform that noninvasively collects saliva metabolic fingerprinting (SMF) by nanoparticle‐enhanced laser desorption–ionization mass spectrometry with high‐reproducibility and high‐throughput, using ultra‐small sample volume (down to 10 nL), is developed. Further, excellent diagnostic performance is achieved with an area‐under‐the‐curve of 0.8496 (95% CI: 0.7393–0.8625) by constructing deep learning model from 312 participants. In conclusion, an alternative solution is provided for the molecular diagnostics of PD with SMF and metabolic biomarker screening for therapeutic intervention. [ABSTRACT FROM AUTHOR]

In this work, FeS supported SBA-15 mesoporous silica catalyst (FeS@SBA-15) was synthesized successfully, characterized and first applied to persulfate (PS) activation for the degradation of imidacloprid in wastewater. The as-prepared 3.5-FeS@SBA-15 presented an impressive imidacloprid removal efficiency of 93.1% and reaction stoichiometric efficiency (RSE) of 1.82% after 5 min, ascribed to the synergetic effects of improved FeS dispersion and abundant surface sites by SBA-15. Electron paramagnetic resonance spectra and quenching experiments proved that both SO4·- and ·OH were produced in FeS@SBA-15/PS system, and SO4·- played a dominant role in the degradation process. The S2- can accelerate the cycling of Fe(III)/Fe(II) during activation and increase the steady-state concentration of Fe(II). More importantly, the constructed heterogeneous system exhibited an efficient and stable catalytic activity over a wide range of pH (3.0-9.0), temperature (283K-313K), inorganic ion (NO3-) and humic acid (1-20 mg/L). Moreover, the density functional theory calculations were conducted to predict the potential reaction sites of imidacloprid. Based on eighteen identified intermediates, four main degradation pathways were proposed: hydroxylation, dechlorination, hydrolysis, and the ring cleavage of the imidazolidine. ECOSAR analysis indicated hydroxylation and dechlorination played a key role in the detoxification of the formed compounds. These findings would provide new insights into the application of FeS@SBA-15 catalyst in wastewater treatment and the removal mechanism of imidacloprid from wastewater. [ABSTRACT FROM AUTHOR]

Background: Language ability differs between the sexes. However, it is unclear how this sex difference is moderated by genetic factors and how the brain interacts with genetics to support this specific language capacity. Previous studies have demonstrated that the sorting protein-related receptor (SORL1) polymorphism influences cognitive function and brain structure differently in males and females and is associated with Alzheimer's disease risk. Objective: The aim of this study was to investigate the effects of sex and the SORL1 rs1699102 (CC versus T carriers) genotype on language. Methods: 103 non-demented Chinese older adults from Beijing Aging Brain Rejuvenation Initiative (BABRI) database were included in this study. Participants completed language tests, T1-weighted structural magnetic resonance imaging (MRI) and resting-state functional MRI. Language test performance, gray matter volume, and network connections were compared between genotype and sex groups. Results: The rs1699102 polymorphism moderated the effects of sex on language performance, with the female having reversed language advantages in T carriers. The T allele carriers had lower gray matter volume in the left precentral gyrus. The effect of sex on language network connections was moderated by rs1699102; male CC homozygotes and female T carriers had higher internetwork connections, which were negatively correlated with language performance. Conclusion: These results suggest that SORL1 moderates the effects of sex on language, with T being a risk allele, especially in females. Our findings underscore the importance of considering the influence of genetic factors when examining sex effects. [ABSTRACT FROM AUTHOR]

Local full-waveform inversion (FWI) methods use redatumed seismic responses of virtual receivers within the subsurface to build the local objective function based on the convolution-type representation theorem. The Marchenko method is widely used to obtain the redatumed data. The method only requires a smoothed velocity model with correct kinematic characteristics of seismic responses for redatuming of the single-sided reflection data. However, the standard Marchenko method is insensitive to lateral propagation of the wavefield. By injecting the standard Marchenko redatumed wavefield along the boundary of the target, the local wavefield propagation modeling produces errors, which affects the accuracy of the local FWI. In this paper, a method to obtain more accurate Green's functions is proposed by incorporating vertical seismic profile data (VSP) into the calculation process of the Marchenko source-receiver redatuming. This method allows one to obtain the accurate laterally propagating waveform, resulting in a significant improvement of lateral resolution. The proposed method is applied to a benchmark model dataset and compared with the local FWI based on standard Marchenko redatuming. [ABSTRACT FROM AUTHOR]

The microbial compositions and metabolites of fermented sauerkraut with and without the addition of microorganisms have been compared. The OTU clustering, nonvolatile compounds, volatile compounds and associations between bacterial taxa and metabolites were analyzed by 16S rRNA high-throughput sequencing technology, ultra performance liquid chromatography (UPLC), gas chromatography ion mobility mass spectrometry (GC-IMS) and the O2PLS model studies. The results showed that at the phylum level, the microbial species in the four sauerkraut types consisted mainly of the phyla Firmicutes and Proteobacteria, but different modes of microbial addition formed their own unique microbial communities. There were significant differences in the microbial communities among different northeast China sauerkraut samples, and different microbial communities exerted similar effects to inhibit Firmicutes production. At the genus level, sauerkraut without added microorganisms had the lowest microbial diversity. A total of 26 amino acids and 11 organic acids were identified and were more abundant in nonmicrobially fermented sauerkraut; 88 volatile organic compounds were identified in the 4 types of sauerkraut, with the microbially fermented sauerkraut being richer in alcohols, esters and acids. Different brands of sauerkraut contain their own unique flavor compounds. Cystine and tyrosine, ascorbic acid and acetic acid, and alcohols and esters are closely related to a wide range of microorganisms in sauerkraut. Elucidating the correlations among microbiota and metabolites will help guide future improvements in sauerkraut fermentation processes. [ABSTRACT FROM AUTHOR]

Odor pollution caused by brownfield site has attracted increasing attention. However, to date, fewer suitable materials can be used to control the emission of odor pollutant from brownfield site during remediation. This study prepared a kind of combined hydrogel solution based on sodium alginate and carboxymethyl cellulose sodium (CHS-SC) and tested the possibility of its membrane in controlling the emission of three odor pollutants (trichloroethylene, dimethyl disulfide, and p-xylene) from polluted soil. Our results showed that CHS-SC membrane could effectively control the emission of three odor pollutants from polluted soil. Comparatively, CHS-SC membrane had higher control rates for three odor pollutants at high ambient temperature (32 °C), short storage time of CHS-SC (5 days, 25 °C), and low odor pollutant concentration (2 ml/kg soil) than at low ambient temperature (2 °C), long storage time of CHS-SC (10 d, 25 °C), and high odor pollutant concentration (4 ml/kg soil), respectively. CHS-SC membrane was degraded by 79.23% after 150 days in soil and slightly changed soil bacterial community, indicating that it had good biodegradability and environmental friendliness. In addition, CHS-SC cost was the lowest among the products with similar function. This study shows that CHS-SC is effective in short-timely controlling the emission of odor pollutants from brownfield site. [ABSTRACT FROM AUTHOR]

This meta‐analysis aimed to investigate the effect of the genotype on the pharmacokinetics and bleeding events of direct oral anticoagulants (DOACs) and comprehensively searched electronic databases. Weighted mean difference (WMD) was used to assess the kinetic indicators, odds ratio, and 95% confidence interval (CI) were used to calculate the clinical outcomes. Thirteen articles with 1543 participants were finally included in this study. The peak concentration (Cmax) and area under the plasma concentration–time curve from time 0 to infinity of individuals with the ABCB1 rs 1045642 CT + TT were higher than that of the CC (WMD = −31.9, 95% CI [−49.94, −12.24], P =.02; WMD = −79.97, 95%CI [−152.38 to −7.56], P =.03, I2 = 0). The Cmax of individuals with mutated genes in ABCB1 2677–3435 is higher than that the wild type (WMD = −19.20, 95%CI [36.62 to −1.79], P =.03, I2 = 0). Carriers of the CYP3A5 rs776746 GG genotype had a higher Cmax than the GA gene (WMD = −51.22, 95%CI [−92.26 to −10.19], P =.01, I2 = 0). Bleeding events were more common in the CES1 rs 2244613 AA + AC than in the CC (odds ratio, 2.62, 95%CI [1.06, 6.47], P =.04; I2 = 0). The Cmax of DOACs was affected by individuals with ABCB1 rs 1045642, ABCB1 2677‐343, and cytochrome P450 3A5 rs 776746. Carriers of the ABCB1 rs 1045642 affected the change of area under the plasma concentration–time curve from time 0 to infinity of DOACs. Bleeding events were affected by CES1 rs 2244613. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the proportion of hidden blood loss (HBL) in patients treated with minimally invasive surgery, and to compare the HBL between patients treated with percutaneous pedicle screw fixation (PPSF) and the mini-open Wiltse approach with pedicle screw fixation (MWPSF). Methods: From January 2017 to January 2019, a total of 119 patients with thoracolumbar fractures were included in the analysis, of which 58 cases received PPSF and 61 cases received MWPSF. The clinical information and demographic results were collected and compared. And the HBL of the patients is calculated by the combination formulas of Nadler, Gross and Sehat. Results: Compared with the PPSF group, operation time of MWPSF is shorter. The fluoroscopy times are 13.6 ± 3.0 in PPSF group and 5.6 ± 1.6 in MWPSF group (p < 0.001). As shown in Table 3, the intraoperative blood loss in PPSF group is 31.9 ± 9.6 ml, which is significantly less than that in the MWPSF group (44.0 ± 14.9 ml). The HBL (445.7 ± 228.9 ml), and HBL% (91.2 ± 7.7%) of the PPSF group are significantly higher than that in the MWPSF group (P < 0.05). And the total blood loss (TBL) of the PPSF group (477.6 ± 228.8 ml) is also more than that in the MWPSF group (401.0 ± 171.3 ml). Conclusions: Our results suggest that in the minimally invasive surgical treatment of thoracolumbar fractures, the perioperative HBL is much higher than visible blood loss (VBL). Although PPSF has less intraoperative blood loss, it has higher TBL and HBL than those of MWPSF. Compared with MWPSF, we should pay more attention to the postoperative anemia status of patients with thoracolumbar fractures undergoing PPSF surgery. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the proportion of hidden blood loss (HBL) in patients treated with minimally invasive surgery, and to compare the HBL between patients treated with percutaneous pedicle screw fixation (PPSF) and the mini-open Wiltse approach with pedicle screw fixation (MWPSF). Methods: From January 2017 to January 2019, a total of 119 patients with thoracolumbar fractures were included in the analysis, of which 58 cases received PPSF and 61 cases received MWPSF. The clinical information and demographic results were collected and compared. And the HBL of the patients is calculated by the combination formulas of Nadler, Gross and Sehat. Results: Compared with the PPSF group, operation time of MWPSF is shorter. The fluoroscopy times are 13.6 ± 3.0 in PPSF group and 5.6 ± 1.6 in MWPSF group (p < 0.001). As shown in Table 3, the intraoperative blood loss in PPSF group is 31.9 ± 9.6 ml, which is significantly less than that in the MWPSF group (44.0 ± 14.9 ml). The HBL (445.7 ± 228.9 ml), and HBL% (91.2 ± 7.7%) of the PPSF group are significantly higher than that in the MWPSF group (P < 0.05). And the total blood loss (TBL) of the PPSF group (477.6 ± 228.8 ml) is also more than that in the MWPSF group (401.0 ± 171.3 ml). Conclusions: Our results suggest that in the minimally invasive surgical treatment of thoracolumbar fractures, the perioperative HBL is much higher than visible blood loss (VBL). Although PPSF has less intraoperative blood loss, it has higher TBL and HBL than those of MWPSF. Compared with MWPSF, we should pay more attention to the postoperative anemia status of patients with thoracolumbar fractures undergoing PPSF surgery. [ABSTRACT FROM AUTHOR]

China is the largest producer and exporter of coke globally, which means that it is very important to understand the characteristics of air pollutants and carbon emissions from China's independent coking industry. This study was the first to establish a bottom-up inventory of the air pollutants and carbon emissions of China's independent coking industry during 2001–2018 based on continuous emission monitoring system online monitoring data and unit-based corporate information. Based on the developed emission inventory, four scenarios were established to analyze potential emissions reduction of air pollutants and carbon dioxide (CO2) in future. The emissions of particulate matter (PM10 and PM2.5), sulfur dioxide (SO2), black carbon (BC) and organic carbon (OC) decreased by 62.11%, 63.41%, 72.85%, 63.41% and 63.41%, respectively. CO2, carbon monoxide (CO), volatile organic compounds (VOCs) and nitrogen oxides (NOX) emissions increased by 355.51%, 355.51%, 355.51% and 99.74%, respectively. In 2018, PM10, PM2.5, SO2, NOx, BC, OC, CO, VOCs and CO2 emissions were, respectively. 45.20, 16.91, 63.84, 117.71, 5.07, 5.92, 554.91, 1026.58 Gg, and 176.88 Tg. Shanxi province made the greatest contributions to the total emissions of air pollutants and CO2 from this industry by 25.01%. The emission source that contributed most to PM2.5 (SO2 and NOX) emissions was coke pushing (quenching and the coke oven chimney respectively) in 2018. Under the ULE scenario (2018–2035), PM2.5 and SO2 emissions will reduce by more than 30%. Under the PCP scenario, PM2.5 and SO2 emissions will reduce by more than 55%. Under the CBP scenario, CO2 emissions will peak at 197.99 Tg in 2025 and decrease to 70% of the peak in 2035. The results showed the emission characteristics of air pollutants and CO2, future emission with several scenarios and cooperative reduction potential in China's independent coking industry, which provides scientific support for the development of pollution control strategies. [ABSTRACT FROM AUTHOR]

With serious environmental, cost, and social concerns arising from emerging countries' rapid growth in agricultural food cold chain (AFCC), AFCC firms urgently require a set of comprehensive sustainable strategic solutions. Therefore, this research identified and modeled the critical success factors (CSFs) that support the sustainable development of AFCCs. The study integrated institutional theory, stakeholder theory, and the triple bottom line model; it also surveyed cold chain experts from 16 different organizations in China and applied the adversarial interpretation structure model (AISM). This comprehensive analysis indicates that managing stakeholder pressure is the most motivating CSF of all strategies. This strategy eventually contributes to the sustainability of AFCC in China by driving other CSFs. Additionally, the study determined the degree of interdependence and dominance of different strategies. Thus, this study establishes a theoretical foundation for the sustainable improvement of AFCC organizations' business strategies and environmental policies. [ABSTRACT FROM AUTHOR]

The ever-increasing morbidity associated with gynecological malignancies constantly endangers the physical and psychological health of women. Since a long time, there has been an urgent need for a deeper understanding of the tumorigenesis and the development of gynecological cancer to identify new molecular markers for early diagnosis and metastatic disease prognosis and for the development of therapeutic targets. MicroRNAs are crucial cellular regulators. The microRNA-10 (miR-10) family has been found to play an integral role in the evolution of numerous cancer types. A comprehensive understanding of current studies on miR-10 could provide better insights into future research and clinical applications in related fields. This article reviews the latest research on the role of the miR-10 family in gynecological malignancies and the relevant molecular mechanism, mainly focusing on endometrial, cervical, and ovarian cancers. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction is high in the elderly population and seriously affects the quality of life. Brain‐derived neurotrophic factor (BDNF) is one of the key neurotrophic proteins, and activation of BDNF–TrkB is considered an effective strategy to improve cognitive dysfunction during aging. In this study, administration of polygonatum sibiricum (PS) for 5 months effectively ameliorates the cognitive function, improving the Nissl body state in cortex and hippocampus in aging rats. In addition, PS can improve the synaptic structure and increase the number of synapses. Furthermore, PS reverses the reduction of synaptic plasticity‐related proteins postsynaptic density protein 95 (PSD‐95) and synaptophysin during aging and up‐regulates the expression of BDNF–TrkB. In conclusion, PS improves cognitive dysfunction and enhances synaptic plasticity in naturally aged rats by regulating the BDNF–TrkB signaling pathway. PS has the potential to be developed as a novel and promising functional health food for the elderly. Practical applications: Polygonatum sibiricum (PS) is a traditional Chinese medicine, which has been included in the homologous plant of medicine and food. PS has been widely used to treat lung diseases, diabetes and antiaging in clinical. Studies have confirmed that PS can accelerate the repair and regeneration of damaged neurons, reverse the changes in synaptic structure, and improve the ability of learning and memory. Our study confirmed that PS significantly improved the cognitive function in aging rats. PS has great potential to be developed as a functional food for improving neurological function and anti‐aging. [ABSTRACT FROM AUTHOR]

Background: DNA methylation is expected to become a kind of new diagnosis and treatment method of Alzheimer's disease (AD). Neuroinflammation- and immune-related pathways represent one of the major genetic risk factors for AD.Objective: We aimed to investigate DNA methylation levels of 7 key immunologic-related genes in peripheral blood and appraise their applicability in the diagnosis of AD.Methods: Methylation levels were obtained from 222 participants (101 AD, 72 MCI, 49 non-cognitively impaired controls). Logistic regression models for diagnosing AD were established after least absolute shrinkage and selection operator (LASSO) and best subset selection (BSS), evaluated by respondent working curve and decision curve analysis for sensitivity.Results: Six differentially methylated positions (DMPs) in the MCI group and 64 in the AD group were found, respectively. Among them, there were 2 DMPs in the MCI group and 30 DMPs in the AD group independent of age, gender, and APOE4 carriers (p <  0.05). AD diagnostic prediction models differentiated AD from normal controls both in a training dataset (LASSO: 8 markers, including methylation levels at ABCA7 1040077, CNR1 88166293, CX3CR1 39322324, LRRK2 40618505, LRRK2 40618493, NGFR 49496745, TARDBP 11070956, TARDBP 11070840 area under the curve [AUC] = 0.81; BSS: 2 markers, including methylation levels at ABCA7 1040077 and CX3CR1 39322324, AUC = 0.80) and a testing dataset (AUC = 0.84, AUC = 0.82, respectively).Conclusion: Our work indicated that methylation levels of 7 key immunologic-related genes (ABCA7, CNR1, CX3CR1, CSF1R, LRRK2, NGFR, and TARDBP) in peripheral blood was altered in AD and the models including methylation of immunologic-related genes biomarkers improved prediction of AD. [ABSTRACT FROM AUTHOR]

The microstructures in the thickening of plasma electrolytic oxidation (PEO) coatings and their effects on the corrosion resistance of the PEO Mg alloys were investigated using x-ray tomography in conjunction with electrochemical impedance spectroscopy (EIS). It was found that the micropores would develop and connect with each other in the thickening of PEO coatings, resulting in the increment of the average diameters and the maximum diameters of the micropores. The thickness of the whole PEO coating gradually increased with oxidation time, and it was beneficial to diminish the through-pores in PEO coatings. The PEO Mg alloy prepared by controlling 40 min oxidation time exhibited the best corrosion resistance because of its larger thickness, denser structure, and higher content of the Mg2SiO4 phase in the PEO coating. Based on equivalent circuits for EIS spectra, the limit value of the low-frequency resistance ( R l ) was used to evaluate the corrosion resistance of the PEO Mg alloys. And that this method was verified by the experimental results. [ABSTRACT FROM AUTHOR]

Solvents, components of pesticide emulsifiable concentrates (ECs), emit quantities of volatile organic compounds (VOCs) into the atmosphere. In the air, their active involvement in oxidative chemical reactions with oxidants exposed to ultraviolet solar radiation can result in the formation of ozone. The quantitative assessment of VOC emissions from agricultural pesticide applications remains hampered by many factors, especially the volatility coefficient of solvents in pesticides. Therefore, this study identified solvents in 20 widely used pesticide products in China. The volatility coefficients of the solvents were investigated based on a spraying test to evaluate VOC emissions from agricultural pesticide applications and their ozone formation potential (OFP). The results suggest that VOC emissions from agricultural pesticide applications amount to 0.60 Mt in 2017, with insecticides, fungicides, and herbicides contributing 0.39 Mt, 0.12 Mt, and 0.09 Mt of VOCs, respectively. Since VOC emission and maximum incremental reactivity (MIR) led to an OFP value (2.1 g ozone/g product) for insecticides, a primary consideration should be to decrease use of solvents with high volatility coefficients and large MIR values in insecticide products. This work could provide valuable insights regarding response options to reduce VOC emissions and ozone formation. [ABSTRACT FROM AUTHOR]

Background and Objectives: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin plus raltitrexed (HAICROX) as an alternative treatment option for advanced hepatocellular carcinoma (HCC) patients who are ineligible for, or failed, the transarterial chemoembolization (TACE) treatment. Materials and Methods: From July 2020 to November 2021, a total of 35 HCC patients were enrolled and received HAIC with oxaliplatin plus raltitrexed. The overall survival (OS) and time to progression (TTP) were primary and secondary endpoints, respectively. The tumor response was assessed by the modified response evaluation criteria in solid tumors (mRECIST), and the adverse events were investigated using the common terminology criteria for adverse events version 5.0 (CTCAE 5.0). Results: The median OS and TTP were 10 months (95% confidence interval (CI): 5.5–14.6) and 3.5 months (95% CI: 2.3–4.7), respectively. By means of multivariate analysis, anti-programmed cell death protein 1 (anti-PD-1) immunotherapy was found to be an independent prognostic factor for better survival. No patients experienced toxicity-related death. Thrombocytopenia, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) elevation were the most common toxicities. No grade 3 or higher adverse events related to HAICROX were observed. Conclusion: HAICROX showed valuable efficacy and tolerable toxicity in advanced HCC patients who progressed on TACE or were ineligible for TACE. HAICROX is a promising treatment for advanced-stage HCC patients with TACE failure or ineligibility. [ABSTRACT FROM AUTHOR]

(1) Objective: to investigate the association between the total burden of cerebral small vessel disease (CSVD) and cognitive function in Parkinson's disease (PD). (2) Methods: this retrospective study compared clinical and neuroimaging characteristics of 122 PD patients to determine the association between cognitive decline and total burden of CSVD in PD. All patients underwent brain MRI examinations, and their total CSVD burden scores were evaluated by silent lacunar infarction (SLI), cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). The cognitive function was assessed by administering Mini-Mental State Examination (MMSE). Receiver-operating characteristic (ROC) curve and the area under the ROC curve (AUC) were performed to quantify the accuracy of the total burden of CSVD and PVH in discriminating PD patients with or without cognitive impairment. (3) Results: the PD patients with cognitive impairment had a significantly higher SLI, CMB, periventricular hyperintensities (PVH), deep white matter hyperintensities (DWMH), enlarged perivascular spaces of basal ganglia (BG-EPVS), and the total CSVD score compared with no cognitive impairment. Total CSVD score and MMSE had a significant negative correlation (r = −0. 483). Furthermore, total burden of CSVD and PVH were the independent risk factors of cognitive impairment in PD, and their good accuracy in discriminating PD patients with cognitive impairment from those with no cognitive impairment was confirmed by the results of ROC curves. (4) Conclusions: total burden of CSVD tightly linked to cognitive impairment in PD patients. The total burden of CSVD or PVH may predict the cognitive impairment in PD. [ABSTRACT FROM AUTHOR]

To reflect the volatile differences of dried citrus peel as affected by cultivars and drying methods, the volatile compounds of dried citrus peel of two cultivars (Citrus reticulata "Chachi" and Citrus reticulata "Ponkan"), prepared under three drying methods (sun-drying (SD), hot-air-drying (AD), and freeze-drying (FD)), were analyzed by GC-MS, odor activity values (OAVs), and GC-IMS. GC-MS data indicated that SD was favorable to preserve terpenic alcohols (linalool, α-terpineol and terpinene-4-ol), β-cymene, methyl methanthranilate, and monoterpenes; while AD was favorable to preserve aliphatic aldehydes and sesquiterpenes; and SD was more similar with AD in GC-MS analysis of volatile profile (of higher MW) for both cultivars from the PCA outcome. Furthermore, significant difference in volatile isomeric composition of different samples was also clearly demonstrated through extracted ion chromatogram (EIC) by GC-MS analysis. GC-IMS analysis showed the favorability of FD to preserve ketones, phenols, esters, and aromatic aldehydes; and SD was more similar with FD in GC-IMS analysis of volatile profile (of smaller MW) for both cultivars from the PCA outcome. Moreover, the OAVs indicate that 2-methoxy-4-vinylphenol contributed much to the flavor of dried Ponkan peel, while 2-methoxy-4-vinylphenol, methyl methanthranilate, and methyl anthranilate played an important role in the flavor of dried Chachi peel; and the highest OAVs for monoterpenes were observed at SD for both cultivars. Thus, the combination of GC-MS and GC-IMS analyses with PCA in this paper suggested the superiority of SD to preserve volatiles and characteristic aroma in dried citrus peel, and that SD contributed much to the quality of dried Chachi peel. [ABSTRACT FROM AUTHOR]

Mutations of the leucine-rich repeat kinase 2 (LRRK2) gene are associated with pronounced sleep disorders or cognitive dysfunction in neurodegenerative diseases. However, the effects of LRRK2 deficiency on sleep rhythms and sleep deprivation-related cognitive changes, and the relevant underlying mechanism, remain unrevealed. In this study, Lrrk2-/- and Lrrk2+/+ mice were subjected to normal sleep (S) or sleep deprivation (SD). Sleep recording, behavioral testing, Golgi-cox staining, immunofluorescence, and real-time PCR were employed to evaluate the impacts of LRRK2 deficiency on sleep behaviors and to investigate the underlying mechanisms. The results showed that after SD, LRRK2-deficient mice displayed lengthened NREM and shortened REM, and reported decreased dendritic spines, increased microglial activation, and synaptic endocytosis in the prefrontal cortex. Meanwhile, after SD, LRRK2 deficiency aggravated cognitive impairments, especially in the recall memory cued by fear conditioning test. Our findings evidence that LRRK2 modulates REM/NREM sleep and its deficiency may exacerbate sleep deprivation-related cognitive disorders by perturbing synaptic plasticity and microglial synaptic pruning in mice. [ABSTRACT FROM AUTHOR]

Understanding the role of agriculture in the development of human societies around the world is an important field of study with many unanswered questions. As a step toward that greater understanding, we have studied the archeobotanical remains at the Jingshuidun site in the mountainous areas of the lower reaches of the Yangtze River in southern Anhui Province which are part of the core area of rice cultivation today. Our analyses of macrobotanical remains and phytoliths formed the basis for the reconstruction of the subsistence economy of ancient humans at the Jingshuidun site from the late Neolithic to early historical times. When our data are combined with that of previous archeobotanical work, we obtain a clearer picture of the development of rice and millet agriculture in the southern Anhui Province region, as well as the spread of millet cultivation. Macrobotanical remains and phytoliths of domesticated rice are present in layers at the Jingshuidun site dated to 4874–4820 cal. yr B.P. (middle-late Liangzhu Period) and 2667–2568 cal. yr B.P. (late Western Zhou Dynasty to the early Spring and Autumn Period). Moreover, macrobotanical remains and phytoliths from the site document the earliest remains of foxtail millet (Setaria italica) in southern Anhui Province, from a layer dating to the late Western Zhou Dynasty and the early Spring and Autumn Period (2667-2568 cal. yr B.P.). These results suggest that the people occupying the Jingshuidun site used single rice farming as far back as 4874–4820 cal. yr B.P., and they began to plant millet by at least 2667–2568 cal. yr B.P., documenting the spread of millet agriculture to the southern area by that time. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver cancer is the second most common cause of cancer-related death, with hepatocellular carcinoma (HCC) being the most prevalent subtype. Transarterial chemoembolization (TACE) in combination with different tyrosine kinase inhibitors (TKIs) has recently been widely used for unresectable HCC (uHCC). However, studies investigating different combinations of agents have shown inconsistent results. Thus, we conducted a network meta-analysis to assess and compare the response of different agents in an uHCC setting. According to our results, TACE plus lenvatinib provides optimal treatment for uHCC, with the highest ranking based on OS, PFS, and DCR rates and the second-best ranking based on ORR rates. Transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) is the mainstay treatment for unresectable hepatocellular carcinoma (uHCC). However, studies investigating different combinations of agents have shown inconsistent results. Here, we used network meta-analysis (NMA) to compare different agents across 41 studies (36 cohort studies and five RCTs) in 11,540 patients. Multiple RCTs and cohort studies were searched to evaluate TACE combined with different TKIs. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and tumor response. NMA used a random-effects consistency model to pool evidence from direct and indirect comparisons. Hazard ratio (HR) and relative risks (RR) with 95% confidence intervals (CI) were analyzed. Further, heterogeneity and publication bias analyses were performed and agents were ranked. TACE plus lenvatinib provided the maximal OS (Rank probability: 0.7559), PFS (Rank probability: 0.8595), CR (Rank probability: 0.4179), and DCR (Rank probability: 0.3857). TACE plus anlotinib demonstrated the highest PR (p = 0.62649) and ORR (p = 0.51158). SD was more often associated with TACE plus sorafenib (Rank probability: 0.601685). TACE plus lenvatinib provides optimal treatment for uHCC based on the highest ranking of OS, PFS, and DCR rates. However, given the lack of statistically significant OS benefit, shared decision making should include other TKIs as acceptable alternatives. [ABSTRACT FROM AUTHOR]

A 56-day feeding trial was conducted to study the effects of dietary nucleotides on growth performance, non-specific immunity, and disease resistance of the juvenile giant freshwater prawn, Macrobrachium rosenbergii (initial weight, 0.095 ± 0.002 g). Five nucleotide levels were set, 0 g/kg, 0.2 g/kg, 0.4 g/kg, 0.8 g/kg, and 1.2 g/kg, respectively. Each group had 3 replicates with 300 prawns per replicate. After the feeding trial, 40 prawns from each pond were challenged with Vibrio anguillarum for 7 days. The results showed that the final body weight (FBW) and weight gain (WG) of 0.4 g/kg nucleotide group were significantly higher than those of the control group. The survival (SR) of 0.2 g/kg nucleotide group was significantly higher than that of the control group. The feed conversion ratio (FCR) of 0.4 g/kg nucleotide group was significantly lower than that of the control group. However, there was no significant difference in specific growth rate (SGR) among the experimental groups and control group. The dry matter, crude protein, and crude fat of prawns fed diet with nucleotides had no obvious trend, and there was no significant difference compared with the control group. The activities of glutamic oxaloacetic transaminase (GOT), superoxide dismutase (SOD), phenoloxidase (PO), acid phosphatase (ACP), and lysozyme (LZM) in serum of prawns were significantly influenced by the nucleotides in diet. The phagocytosis rate and phagocytic index of hemocyte were significantly higher in the nucleotide group. Finally, the average mortality of prawns infected with Vibrio anguillarum was also significantly affected by nucleotides, and the relative percent survival (RPS) was more than 50% when the nucleotide level was 0.4–1.2 g/kg. In summary, dietary with 0.2–0.4 g/kg nucleotides promoted the growth performance, enhanced the immunity, and improved the disease resistance of M. rosenbergii. [ABSTRACT FROM AUTHOR]

Stress may serve multiple roles in cerebral functioning, ranging from a highly appropriate behavioral adaptation to a critical risk factor for susceptibility to mood disorder and cognitive impairment. It is well known that E/I (excitation/inhibition) balance is essential for maintaining brain homeostasis. However, it remains largely unknown how GABAergic and Glutamatergic neurons respond to different stressful stimuli and whether the GABAergic-Glutamatergic neuron balance is related to the transition between adaptive and maladaptive behaviors. Here, we subjected 3-month-old mice to chronic mild stress (CMS) for a period of one, two, and four weeks, respectively. The results showed that the two-week CMS procedure produced adaptive effects on behaviors and cognitive performance, with a higher number of GABAergic neuron and VGluT1-positive neurons, increasing the expressions of p-GluN2B, Reelin, and syn-PSD-95 protein in the hippocampus. In contrast, the prolonged behavioral challenge (4 week) imposes a passive coping behavioral strategy and cognitive impairment, decreased the number of GABAergic neuron, hyperactivity of VGluT1-positive neuron, increased the ratio of p-GluN2B, and decreased the expression of Reelin, syn-PSD-95 in the hippocampus. These findings suggest that a moderate duration of stress probably promotes behavioral adaptation and spatial memory by maintaining a GABAergic-Glutamatergic neuron balance and promoting the expression of synaptic plasticity-related proteins in the brain. [ABSTRACT FROM AUTHOR]

Background and Objectives: The recurrence outcome in patients who underwent microwave ablation (MWA) with or without transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) within Milan criteria remains unclear. The aim of this retrospective study was to identify the predictive factors of recurrence in these patients. Materials and Methods: From May 2018 to April 2021, 66 patients with HCC within Milan criteria were enrolled. Local tumor progression (LTP) and recurrence-free survival (RFS) were evaluated. Univariate and multivariate analyses were used to evaluate the risk factors of recurrence. The propensity score analysis was conducted to reduce potential confounding bias. Results: During the median follow-up of 25.07 months (95% confidence interval [CI], 21.85, 28.28), the median time to LTP and RFS were 20.10 (95%CI, 14.67, 25.53) and 13.03 (95%CI, 6.36, 19.70) months. No group difference (MWA vs. MWA + TACE) was found in 1-year cumulative LTP (p = 0.575) and RFS (p = 0.515), but meaningful significant differences were found in two-year recurrence (LTP, p = 0.007 and RFS, p = 0.037). Univariate and multivariate analyses revealed that treatment received before ablation was an independent risk factor of LTP (hazard ratio [HR] 4.37, 95%CI, 1.44, 13.32) and RFS (HR 3.41, 95%CI, 1.49, 7.81). Conclusions: The LTP and RFS in the MWA group were similar to that in the MWA combined with TACE. For HCC within Milan criteria, both groups preferentially selected MWA. More endeavor and rigorous surveillance should be taken to relapse prevention, in patients who have received previous treatment. [ABSTRACT FROM AUTHOR]

The tumor‐suppressor role of long noncoding RNA (lncRNA) growth arrest‐specific transcript 5 (GAS5) has been proven in various types of cancer. However, the specific function of GAS5 in tumor‐associated macrophages (TAMs) of endometrial cancer (EC) is elusive. Quantitative PCR results showed that GAS5 expression decreased in EC tissues and primary TAMs from EC tumors. Tumor‐associated macrophage infiltration was significantly positively associated with the developmental stage of EC. Direct coculture of GAS5‐overexpressing TAMs and EC cells showed that GAS5 enhanced phagocytosis, antigen presentation, and activation of cytotoxic T cells, and repressed "Don't eat me" signals between TAMs and EC cells. Tumor formation in immunodeficient mice showed that GAS5‐overexpressing macrophages could repress EC formation in vivo. GAS5 promoted M1 polarization by activating the microRNA‐21– phosphatase and tensin homolog (PTEN)–AKT signaling pathway and directly repressing the nuclear accumulation and phosphorylation of oncogenic yes‐associated protein 1 (YAP1) in TAMs. GAS5 inhibited the development of EC from both innate and adaptive immunity by transforming TAMs from a protumor to an antitumor phenotype. These antitumor effects of GAS5 on TAMs were mediated by the activation of the miR‐21‐PTEN‐AKT pathway and inhibition of YAP1. [ABSTRACT FROM AUTHOR]

In this paper, the silane-based sol–gel treatment process was applied to the plasma electrolytic oxidation (PEO) ZM6 Mg-alloy. The microstructural characteristics and corrosion resistance of the PEO/organic composite coatings were studied by means of SEM and XRT in conjunction with electrochemical measurements. The results showed that the microdefects in the PEO coating could be effectively filled with the silane compounds, reducing the porosity of the PEO coating. The treated PEO coating had a hydrophobic property, which may be related to the siloxane network (Si–O–Si) formed on the PEO coating surface. The corrosiveness of the silane agent to the PEO coating and the generation of internal stress in the PEO coating resulted in the damage of microstructures of the PEO coating. The global and local electrochemical measurements showed that the corrosion-resistant performance of the PEO Mg-alloys after the silane-based sol–gel treatment was improved and its service life would be shortened by the balance of micropores without sealing and the damaged microstructure. [ABSTRACT FROM AUTHOR]

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of autosomal dominant Parkinson's disease (PD), producing psychiatric and motor symptoms. We conducted this study to explore whether microglial dopaminergic (DAergic) fiber refinement and synaptic pruning are involved in the abnormal behavioral phenotypes of carriers of the LRRK2 G2019S mutation, by employing young and middle-aged PD model mice. The results revealed a characteristic late-onset hyperactivity and a progressive decline in the motor coordination of the LRRK2 G2019S mutation mice. LRRK2 G2019S mutation-induced aberrant microglial morphogenesis, with more branches and junctions per cell, resulted in excessive microglial refinement of dopaminergic (DAergic) fibers. Moreover, aberrant synaptic pruning distinctly impacted the prefrontal cortex (PFC) and dorsal striatum (DS), with significantly higher spine density in the PFC but the opposite effects in the DS region. Furthermore, LRRK2 G2019S mutation remodeled the inflammatory transcription landscape of microglia, rendering certain cerebral areas highly susceptible to microglial immune response. These findings indicate that LRRK2 G2019S mutation induces the production of inflammatory cytokines and mediates abnormal microglial morphogenesis and activity, resulting in abnormal phagocytosis, synaptic pruning and loss of DAergic fibers during aging, and, eventually, PD-related behavioral abnormalities. [ABSTRACT FROM AUTHOR]

Biomarker testing is recommended for the accurate and timely diagnosis of Alzheimer's disease (AD). Using illustrative case narratives we consider how cerebrospinal fluid (CSF) biomarker tests may be used in different presentations of cognitive impairment to facilitate timely and differential diagnosis, improving diagnostic accuracy, providing prognostic information, and guiding personalized management in diverse scenarios. Evidence shows that (1) CSF ratios are superior to amyloid beta (Aβ)1‐42 alone; (2) concordance of CSF ratios to amyloid positron emission tomography (PET) is better than Aβ1‐42 alone; and (3) phosphorylated tau (p‐tau)/Aβ1‐42 ratio is superior to p‐tau alone. CSF biomarkers are recommended for the exclusion of AD as the underlying cause of cognitive impairment, diagnosis of AD at an early stage, differential diagnosis of AD in individuals presenting with other neuropsychiatric symptoms, accurate diagnosis of AD in an atypical presentation, and for clinical trial enrichment. Highlights: Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker testing may be underused outside specialist centers.CSF biomarkers improve diagnostic accuracy, guiding personalized management of AD.CSF ratios (amyloid beta [Aβ]1‐42/Aβ1‐40 and phosphorylated tau/Aβ1‐42) perform better than single markers.CSF ratios produce fewer false‐negative and false‐positive results than individual markers.CSF biomarkers should be included in diagnostic work‐up of AD and mild cognitive impairment due to AD. [ABSTRACT FROM AUTHOR]