A novel "de-tension"-guided anterior decompression strategy- thoracic anterior controllable antedisplacement fusion (TACAF) for multilevel ossification of posterior longitudinal ligament in thoracic spine: a retrospective study with at least 2-year follow-up.

PURPOSE: To propose a novel surgical strategy-thoracic anterior controllable ante-displacement fusion (TACAF) to treat mT-OPLL, and investigated its safety and efficacy. METHODS: Between January 2019 and December 2021, a total of 49 patients with thoracic myelopathy due to mT-OPLL were surgically treated with TACAF were retrospectively reviewed. Patients' demographic data, radiological parameters, and surgery-related complications, m-JOA and VAS scores, thoracic kyphosis (TK), kyphosis angle in fusion area (FSK), thoracic curvature, spinal cord curvature and curvature of curved rod in surgical region, diameter and area of the spinal cord at the most compressed level were included. RESULTS: All patients acquired satisfactory recovery of neurological function and overall complication rate is low at the final follow up. The mean m-JOA of the two groups respectively was 3.74±2.05, 3.67±1.95 before surgery, and 9.97±0.83, 9.80±0.68at the final followed up, with the recovery rate of 84.26±14.20,82.79±10.35%, as to VA Scores. the mean FSK was 34.50±4.46,35.33±3.44before surgery, and was restored to 20.97±5.70,22.93±6.34at the final followed up respectively, as to mean TK. (P<0.05). Spinal cord curvature was improved from 34.12±3.59,33.93±3.45before surgery to 19.47±3.53,18.80±3.17at the final follow-up respectively, as to thoracic curvature (P<0.05), and In addition, the area and diameter of the spinal cord was also significantly improved at the final follow up (all P<0.05). The curvature of the thoracic pulp and thoracic vertebra is closely related to the curvature of the rod. There was no statistically significant difference in the incidence of the pelvis and the slope value of the sacrum. CONCLUSIONS: This strategy provides a novel solution for the treatment of mT-OPLL with favorable recovery of neurological function, the tension of spinal cord, and less complications.

Social isolation and the risk of Parkinson disease in the UK biobank study.

Parkinson disease (PD) has become one of the most rapidly growing causes of disability among the older population and social isolation is a major concern in the PD community. However, the relationship between social isolation and future risk of PD remains unclear. This study included 192,340 participants aged 60 or older who were free of dementia and PD at baseline from the UK Biobank study. Social isolation was measured using a composite score derived from three questions on number in household, frequency of friend/family visits, and leisure/social activities. Incident PD cases were identified through electronic health records. Multivariable-adjusted Cox regression models were used to compute the hazard ratio (HR) and 95% confidence interval (CI). Among the 192,340 participants (mean [standard deviation] age, 64.2 [2.9] years; 103,253 [53.7%] women), 89,075 (46.3%) participants were in the least isolated group and 26,161 (13.6%) were in the most isolated group. Over a median follow-up of 12.5 years, 2048 incident PD cases were documented. Compared to the least isolated group, the multivariable-adjusted HRs (95% CIs) for PD were 1.00 (0.91-1.10) for the moderately isolated group and 1.19 (1.05-1.36) for the most isolated group (P-trend = 0.04). The observed association was independent of the genetic susceptibility to PD and consistent in subgroup analyses. Social isolation was associated with a higher risk of PD regardless of genetic risk. Our findings highlighted the importance of developing screening and intervention strategies for social isolation among older adults to reduce the risk of PD.

Association of Cancer History with Lifetime Risk of Dementia and Alzheimer's Disease.

Background: The literature presents conflicting results regarding the potential protective effect of prevalent cancer on the development of dementia and Alzheimer's disease (AD). Objective: Association between cancer and subsequent risk of dementia and/or AD was reported previously, but survival bias has been of concern. Here, we aimed to calculate the lifetime risk of dementia and AD and evaluate the association of cancer history with these two conditions. Methods: In this retrospective analysis, we included 292,654 participants aged 60+ y during the follow-up and free of dementia at baseline, within the UK Biobank cohort. Lifetime risks of dementia and AD were estimated in individuals with and without cancer history, and different durations of cancer exposure and cancer types. Results: During a median of 12.5 follow-up years, 5,044 new dementia and 2,141 AD cases were reported. Lifetime risks of dementia and AD were lower in cancer survivors compared to those without cancer, and this effect was more pronounced in participants with cancer history exposure≥5 years. Similar relationship was observed in individual cancer types, except for breast cancer. Conclusions: Results suggested an inverse association between cancer history and lifetime risk of dementia and AD, which may be modified by different cancer types and cancer exposure time.

How to identify and quantify the members of the Bacillus genus?

Members of the Bacillus genus are widely distributed throughout natural environments and have been studied for decades among others for their physiology, genetics, ecological functions, and applications. However, despite its prevalence in nature, the characterization and classification of Bacillus remain challenging due to its complex and ever-evolving taxonomic framework. This review addresses the current state of the Bacillus taxonomic landscape and summarizes the critical points in the development of Bacillus phylogeny. With a clear view of Bacillus phylogeny as a foundation, we subsequently review the methodologies applied in identifying and quantifying Bacillus, while also discussing their respective advantages and disadvantages.

Machine learning-based prediction model for myocardial ischemia under high altitude exposure: a cohort study.

High altitude exposure increases the risk of myocardial ischemia (MI) and subsequent cardiovascular death. Machine learning techniques have been used to develop cardiovascular disease prediction models, but no reports exist for high altitude induced myocardial ischemia. Our objective was to establish a machine learning-based MI prediction model and identify key risk factors. Using a prospective cohort study, a predictive model was developed and validated for high-altitude MI. We consolidated the health examination and self-reported electronic questionnaire data (collected between January and June 2022 in 920th Joint Logistic Support Force Hospital of china) of soldiers undergoing high-altitude training, along with the health examination and second self-reported electronic questionnaire data (collected between December 2022 and January 2023) subsequent to their completion on the plateau, into a unified dataset. Participants were subsequently allocated to either the training or test dataset in a 3:1 ratio using random assignment. A predictive model based on clinical features, physical examination, and laboratory results was designed using the training dataset, and the model's performance was evaluated using the area under the receiver operating characteristic curve score (AUC) in the test dataset. Using the training dataset (n = 2141), we developed a myocardial ischemia prediction model with high accuracy (AUC = 0.86) when validated on the test dataset (n = 714). The model was based on five laboratory results: Eosinophils percentage (Eos.Per), Globulin (G), Ca, Glucose (GLU), and Aspartate aminotransferase (AST). Our concise and accurate high-altitude myocardial ischemia incidence prediction model, based on five laboratory results, may be used to identify risks in advance and help individuals and groups prepare before entering high-altitude areas. Further external validation, including female and different age groups, is necessary.

Elevated first-trimester neutrophil elastase and proteinase 3 increase the risk of gestational diabetes mellitus and adverse fetal outcomes.

BACKGROUND: Chronic inflammation plays a vital role in the development of gestational diabetes mellitus (GDM). Studies in mouse models show that neutrophil serine proteases (NSPs), neutrophil elastase (NE) and proteinase-3 (PR3) are important drivers of chronic inflammation with consequent metabolic disturbances. This study evaluated the association of NE and PR3 with GDM development and adverse fetal outcomes. METHOD(S): This was a prospective cohort study. Serum PR3 and NE concentration was measured in all enrolled pregnant women in the first and the second trimester to determine the connection between NSPs and GDM and adverse fetal outcomes. Logistic regression, spline regression and linear regression analyses were applied to investigate the association of NE or PR3 with GDM development and adverse fetal outcomes. The concentration of NE and PR3 in placental biopsies was evaluated by semi-quantitative analysis of immunohistochemistry staining. RESULT(S): NE or PR3 concentration in the first trimester, rather than the second, increased more significantly in women with GDM than in those without, regardless of pre-pregnancy body mass index and age. There was a stepwise increase in GDM occurrence as well as comprehensive adverse fetal outcomes across tertiles of NE and PR3. NE and PR3 were positively associated with neutrophil count, pre-pregnancy BMI, plasma glucose level and newborn weight. Logistic regression revealed NE or PR3 to be independent risk factors for the development of GDM and comprehensive adverse fetal outcomes. Spline regression showed a significant increased risk of GDM occurrence and comprehensive adverse fetal outcomes when serum NE concentration exceeded 417.60 ng/mL and a similar result for PR3 and GDM occurrence when the latter exceeded 88.52 ng/mL. Immunohistochemistry data confirmed that enriched NE and PR3 content in placental tissue may have contributed to the development of GDM. CONCLUSION(S): This work demonstrates that excessive first-trimester NE and PR3 increase the risk of GDM development and comprehensive adverse fetal outcomes.

Prevalence and risk factors of dental fluorosis among children aged 8-12 years in Shandong province of China.

This study was to investigate the prevalence and severity of children's dental fluorosis (DF) in Shandong and identified the potential risk factors for DF. A total of 87 villages in Shandong were investigated to calculate the prevalence of DF and Community Fluorosis Index (CFI) in 2018-2019. Six hundred and seventy children were enrolled to identify the potential risk factors using univariate and multivariate logistic regressions. Goodman-Kruskal Gamma was used to explore the factors related to the severity of DF. In 87 villages, 1249 of 8700 (14.36%) children still have DF. The prevalence of DF in most villages was below 40% in 2018-2019. Water fluorine concentration when selected for the study and urinary fluorine concentration were related to the risk of DF (P < 0.001). Some eating habits, like lower frequency of eating fresh vegetables, eggs, and beans, were associated with the risk of DF (P < 0.001). The high water fluorine concentration, and lower frequency of eating fresh vegetables, eggs, and beans were also related to the severity of DF (P < 0.001). DF in children in Shandong province is still a common endemic disease. This study tries to provide a useful guide for the prevention and control of DF.

Family History of AD/Dementia, Polygenic Risk Score for AD, and Parkinson's Disease.

Background: Co-occurrence of Alzheimer's disease (AD) and Parkinson's disease (PD) has been observed. However, there is limited knowledge on how family history of AD is associated with PD. Objectives: To prospectively examine the associations of family history of AD/dementia and polygenic risk score for AD (AD-PRS) with PD risk. Methods: The study included 477,190 participants from UK Biobank who were free of PD at baseline (2006-2010) and had complete data on the studied exposure variables, family history of AD and AD-PRS. Cox proportional hazards model was used to examine the hazard ratios (HRs) and their 95% confidence intervals (CIs) of family history of AD/dementia and AD-PRS for PD risk. We also conducted mediation analysis to examine the proportion of the association between family history of AD/dementia and PD risk that could be mediated by AD-PRS. Results: During a median follow-up of 12.5 years, we identified 2550 incidences of PD. Family history of AD/dementia (adjusted HR = 1.21; 95% CI 1.09-1.35) and AD-PRS (adjusted HR = 1.10 per 1 unit increment; 95% CI 1.05-1.14) were associated with PD risk, after adjustment for age, sex, lifestyle factors, and other potential confounders. The association between family history of AD/dementia and PD risk was mediated by 13.1% by the AD-PRS. As expected, we observed significant associations of family history of AD/dementia and AD-PRS with risks of dementia and AD (P < 0.001 for all). Conclusions: Family history of AD/dementia appeared to be associated with PD risk, and this association could be mediated partially by AD-related genetic factors.

Enhanced specificity of Bacillus metataxonomics using a tuf-targeted amplicon sequencing approach.

Bacillus species are ubiquitous in nature and have tremendous application potential in agriculture, medicine, and industry. However, the individual species of this genus vary widely in both ecological niches and functional phenotypes, which, hence, requires accurate classification of these bacteria when selecting them for specific purposes. Although analysis of the 16S rRNA gene has been widely used to disseminate the taxonomy of most bacterial species, this gene fails proper classification of Bacillus species. To circumvent this restriction, we designed novel primers and optimized them to allow exact species resolution of Bacillus species in both synthetic and natural communities using high-throughput amplicon sequencing. The primers designed for the tuf gene were not only specific for the Bacillus genus but also sufficiently discriminated species both in silico and in vitro in a mixture of 11 distinct Bacillus species. Investigating the primers using a natural soil sample, 13 dominant species were detected including Bacillus badius, Bacillus velezensis, and Bacillus mycoides as primary members, neither of which could be distinguished with 16S rRNA sequencing. In conclusion, a set of high-throughput primers were developed which allows unprecedented species-level identification of Bacillus species and aids the description of the ecological distribution of Bacilli in various natural environment.

The circadian clock of the bacterium B. subtilis evokes properties of complex, multicellular circadian systems.

Circadian clocks are pervasive throughout nature, yet only recently has this adaptive regulatory program been described in nonphotosynthetic bacteria. Here, we describe an inherent complexity in the Bacillus subtilis circadian clock. We find that B. subtilis entrains to blue and red light and that circadian entrainment is separable from masking through fluence titration and frequency demultiplication protocols. We identify circadian rhythmicity in constant light, consistent with the Aschoff's rule, and entrainment aftereffects, both of which are properties described for eukaryotic circadian clocks. We report that circadian rhythms occur in wild isolates of this prokaryote, thus establishing them as a general property of this species, and that its circadian system responds to the environment in a complex fashion that is consistent with multicellular eukaryotic circadian systems.

DNA Nanobarrel-Based Drug Delivery for Paclitaxel and Doxorubicin.

Co-delivery of anticancer drugs and target agents by endogenous materials is an inevitable approach towards targeted and synergistic therapy. Employing DNA base pair complementarities, DNA nanotechnology exploits a unique nanostructuring method and has demonstrated its capacity for nanoscale positioning and templated assembly. Moreover, the water solubility, biocompatibility, and modifiability render DNA structure suitable candidate for drug delivery applications. We here report single-stranded DNA tail conjugated antitumor drug paclitaxel (PTX), and the co-delivery of PTX, doxorubicin and targeting agent mucin 1 (MUC-1) aptamer on a DNA nanobarrel carrier. We investigated the effect of tail lengths on drug release efficiencies and dual drug codelivery-enabled cytotoxicity. Owing to the rapidly developing field of structural DNA nanotechnology, functional DNA-based drug delivery is promising to achieve clinical therapeutic applications.

Perilipin5 protects against non-alcoholic steatohepatitis by increasing 11-Dodecenoic acid and inhibiting the occurrence of ferroptosis.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a major contributor to liver cirrhosis and hepatocellular carcinoma. There remains no effective pharmacological therapy. The hepatic lipid metabolism and fatty acid ß-oxidation are regulated by Perilipin5 (Plin5). However, it is yet unknown how Plin5 affects NASH and the molecular process. METHODS: High-fat, high-cholesterol and high-fructose (HFHC) diets were used to mimic the progression of NASH in wild type (WT) mice and Plin5 knockout (Plin5 KO) mice. The degree of ferroptosis was measured by detecting the expression of key genes of ferroptosis and the level of lipid peroxide. The degree of NASH was judged by observing the morphology of the liver, detecting the expression of inflammation and fibrosis related genes of liver damage. Plin5 was overexpressed in the liver of mice by tail vein injection of adenovirus, and the process of NASH was simulated by methionine choline deficiency (MCD) diet. The occurrence of ferroptosis and NASH was detected by the same detection method. Targeted lipidomics sequencing was used to detect the difference in free fatty acid expression in the WT Plin5 KO group. Finally, it was verified in cell experiments to further study the effect of free fatty acids on ferroptosis of hepatocytes. RESULTS: In various NASH models, hepatic Plin5 was dramatically reduced. Plin5 knockout (KO) worsened NASH-associated characteristics in mice given a high-fat/high-cholesterol (HFHC) diet, such as lipid accumulation, inflammation and hepatic fibrosis. It has been shown that ferroptosis is involved in NASH progression. We revealed that Plin5 KO in mice aggravated the degree of ferroptosis in NASH models. Conversely, overexpression of Plin5 significantly alleviated ferroptosis and further ameliorated progression of MCD-induced NASH. Analysis of livers obtained from HFHC diet-fed mice by targeted lipidomics revealed that 11-Dodecenoic acid was significantly decreased in Plin5 KO mice. Addition of 11-Dodecenoia acid to Plin5 knockdown hepatocytes effectively prevented ferroptosis. CONCLUSION: Our study demonstrates that Plin5 protects against NASH progression by increasing 11-Dodecenoic acid level and further inhibiting ferroptosis, suggesting that Plin5 has therapeutic potential as a target for the management of NASH.

Soluble, Diferuloylated Corn Bran Glucuronoarabinoxylans Modulate the Human Gut Microbiota In Vitro.

Corn bran is exceptionally rich in substituted glucuronoarabinoxylan polysaccharides, which are monoferuloylated and cross-linked by diferulic acid moieties. Here, we assessed the potential prebiotic activity of three enzymatically solubilized corn bran glucuronoarabinoxylans: medium feruloylated (FGAX-M), laccase cross-linked FGAX-M (FGAX-H), and alkali-treated FGAX-M devoid of feruloyl substitutions (FGAX-B). We examined the influence of these soluble FGAX samples on the gut microbiome composition and functionality during in vitro simulated colon fermentations, determined by 16S rRNA gene amplicon sequencing and assessment of short-chain fatty acid (SCFAs) production. All FGAX samples induced changes in the relative composition of the microbiota and the SCFA levels after 24 h of in vitro fermentation. The changes induced by FGAX-M and FGAX-H tended to be more profound and more similar to the changes induced by inulin than changes conferred by FGAX-B. The microbiota changes induced by FGAX-M and FGAX-H correlated with an increase in the relative abundance of Anaerostipes and with increased butyric acid production, while the changes induced by the FGAX-B sample were less compelling. The results imply that solubilized, substituted diferuloylated corn bran glucuronoarabinoxylans may be potential prebiotic candidates and that both single feruloylations and diferuloyl cross-links influence the prebiotic potential of these arabinoxylan compounds.

Acid/Base-Steered Cascade Cyclization: An Efficient One-Pot Access to Diverse Isobenzofuranone and Isoindolobenzoxazinone Derivatives.

We herein report the acid/base-steered two distinct reaction pathways of 2-acylbenzoic acids with isatoic anhydrides. In the presence of Na2CO3, the cascade process consists of the cyclization of 2-acetylbenzoic acid and nucleophilic ring-opening reaction of isatoic anhydride to furnish isobenzofuranone derivatives with high efficiency. However, p-toluenesulfonic acid can promote the product isobenzofuranones to undergo sequential intramolecular rearrangment, nucleophilic addition and cyclization reaction to produce diverse isoindolobenzoxazinones in good yields. The synthetic utility of this method was further demonstrated by the gram-scale preparation of the desired products and the facile transformations of the resulting products.

Respiratory immune status and microbiome in recovered COVID-19 patients revealed by metatranscriptomic analyses.

Coronavirus disease 2019 (COVID-19) is currently a severe threat to global public health, and the immune response to COVID-19 infection has been widely investigated. However, the immune status and microecological changes in the respiratory systems of patients with COVID-19 after recovery have rarely been considered. We selected 72 patients with severe COVID-19 infection, 57 recovered from COVID-19 infection, and 65 with non-COVID-19 pneumonia, for metatranscriptomic sequencing and bioinformatics analysis. Accordingly, the differentially expressed genes between the infected and other groups were enriched in the chemokine signaling pathway, NOD-like receptor signaling pathway, phagosome, TNF signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, and C-type lectin receptor signaling pathway. We speculate that IL17RD, CD74, and TNFSF15 may serve as disease biomarkers in COVID-19. Additionally, principal coordinate analysis revealed significant differences between groups. In particular, frequent co-infections with the genera Streptococcus, Veillonella, Gemella, and Neisseria, among others, were found in COVID-19 patients. Moreover, the random forest prediction model with differential genes showed a mean area under the curve (AUC) of 0.77, and KCNK12, IL17RD, LOC100507412, PTPRT, MYO15A, MPDZ, FLRT2, SPEG, SERPINB3, and KNDC1 were identified as the most important genes distinguishing the infected group from the recovered group. Agrobacterium tumefaciens, Klebsiella michiganensis, Acinetobacter pittii, Bacillus sp. FJAT.14266, Brevundimonas naejangsanensis, Pseudopropionibacterium propionicum, Priestia megaterium, Dialister pneumosintes, Veillonella rodentium, and Pseudomonas protegens were selected as candidate microbial markers for monitoring the recovery of COVID patients. These results will facilitate the diagnosis, treatment, and prognosis of COVID patients recovering from severe illness.

Is there crosstalk between circadian clocks in plants and the rhizomicrobiome?

Circadian clocks occur across the kingdoms of life, including some fungi and bacteria present in the root-associated soil known as the rhizosphere. Recent work from Amy Newman and colleagues, published in BMC Biology, has discovered that the circadian clock in Arabidopsis plants affects the rhythmicity of rhizosphere microbial communities This brings into play the exciting question of whether there is a bidirectional rhythmic interaction between plants and their rhizomicrobiome. Here, we discuss how the findings of Newman et al. suggest that soil microbiomes can have both self-sustained and plant-imposed rhythmicity, and the challenges of plant-microbiome circadian clock research.

Effect of the FA2H Gene on cashmere fineness of Jiangnan cashmere goats based on transcriptome sequencing.

BACKGROUND: Cashmere goats are a heterogeneous hairy mammal. The fineness of cashmere can affect its economic value. Therefore, in this study, we used transcriptome sequencing techniques to analyze the gene expression profiles of the skin tissues of cashmere goats with different cashmere fineness. The selected candidate genes were functionally verified with the secondary hair follicle hair papillary cells of cashmere goats. RESULTS: We identified 479 DEGs, of which 238 mRNAs were up-regulated in the fine velvet group and 241 mRNA were down-regulated. Based on functional annotation and protein interaction network analysis, we found some genes that may affect the fineness of cashmere, including SOX18, SOX4, WNT5A, IGFBP4, KAP8, KRT36, and FA2H. Using qRT-PCR, Western blot, CCK-8 cell viability detection, EDU cell proliferation detection, and flow cytometry, we found that overexpression of the FA2H gene could promote the proliferation of secondary hair follicle DPCs in cashmere goats. At the same time, we proved that FA2H could regulate the expression levels of the FGF5 and BMP2 genes in DPCs. CONCLUSION: The results of this study provide a useful reference for the genetics and breeding of Jiangnan cashmere goats and goat genome annotation, and provide an experimental basis for improving cashmere quality of the cashmere goat.

Different Lewis Acid Promotor-Steered Highly Regioselective Phosphorylation of Tertiary Enamides.

Different Lewis acid promotor-steered highly regioselective phosphorylation of tertiary enamides with diverse H-phosphonates or H-phosphine oxides was developed. Under the catalysis of iron salt, the phosphonyl group was introduced into the α-position of tertiary enamides, affording various α-phosphorylated amides in high efficiency. On the other hand, the ß-phosphorylated tertiary enamides were efficiently obtained as the products in the presence of manganese(III) acetylacetonate.

Manganese(III)-promoted highly stereoselective phosphorylation of acyclic tertiary enamides to synthesize E-selective ß-phosphoryl enamides.

A concise manganese(III)-promoted stereoselective ß-phosphorylation of acyclic tertiary enamides and diverse H-phosphine oxides was achieved. This reaction proceeds with absolute E-selectivity in contrast to Z-selectivity obtained in other previous works and affords various E-selective ß-phosphorylated tertiary enamides in high efficiency. To the best of our knowledge, this is the first case of E-selective ß-phosphorylation of tertiary enamides through C-H functionalization. In addition, the method features broad substrate scope, good functional group compatibility and efficient scale-up.

Non-Destruction Evaluation Method for Long-Term Oxidation Behavior of SiC/SiC Composites with Different Preforms in Wet Oxygen.

The implementation of SiC fiber reinforced SiC/SiC composites to aero-engine hot components has attracted wide attention, due to their many excellent properties. Along these lines, in order to predict the oxidation behavior of the material in extreme environments and to explore the effect of different preforms on the oxidative behavior of the composites, four SiC/SiC composites, with different preforms, were oxidized under environmental conditions of pressure of 12 kPa H2O:8 kPa O2:80 kPa Ar, at 1400 °C temperature. Moreover, the morphology and defect distribution of the samples were characterized by carrying out scanning electron microscopy, and micro-computed X-ray tomography measurements. Furthermore, the relation between the micro- and macro-scales was established, so as to be able to predict the oxidation behavior of the composites; not only the quantitative relationship between the mass change rate and the defect volume change rate, but also the combination of micro-computed X-ray images.