Association of lipid accumulation product with all-cause and cardiovascular disease mortality: Result from NHANES database.

BACKGROUND AND AIM: At present, there are few studies on the relationship between lipid accumulation product (LAP) and mortality. This study aims to explore the relationship between adult LAP and all-cause and cardiovascular disease (CVD) mortality. METHODS AND RESULTS: The study people from the National Health and Nutrition Examination Survey (NHANES). Results of the mortality study were based on death data up to December 31, 2019. Cox proportional risk model was used to estimate the risk ratio (HR) and 95 % CI of all-cause and CVD mortality. A total of 50162 people were included in the study (the weighted average age and male proportion were 48.14 years and 48.64 % respectively). During the follow-up of 203460871 person-years, 6850 deaths were recorded, including 1757 CVD deaths. After multivariable adjustment, the increase of LAP was significantly correlated with all-cause and CVD mortality. Compared with the participants of Quartile 1 of LAP, the multivariable adjusted HRs and 95 % CI of the participants of Quartile 4 of LAP were 1.54 (1.32, 1.80) all-cause mortality (P for trend<0.001), and 1.55 (1.16, 2.09) CVD mortality (P for trend = 0.04). For every increase of natural log-transformed LAP, the all-cause mortality increased by 22 %, and the CVD mortality increased by 14 % (both P < 0.05). CONCLUSIONS: Our cohort study based on NHANES showed that higher LAP was significantly associated with higher all-cause and CVD mortality. Maintaining a low LAP status may reduce the risk of death.

[Effect of Modified Xiaoyao Powder on intestinal barrier and intestinal flora in mice with metabolic associated fatty liver disease based on "gut-liver axis"].

This study explores the effects and mechanisms of Modified Xiaoyao Powder on the intestinal barrier and intestinal flora in mice with metabolic associated fatty liver disease(MAFLD) based on the " gut-liver axis". Sixty male C57BL/6 mice were randomly divided into the normal group, model group, bifidobacterium tetrad tablet group(SQ), and Modified Xiaoyao Powder groups with low,medium and high doses(XL, XM, XH), with 10 mice in each group. All the mice were administrated with a high-fat diet to build the MAFLD model except the normal group and then treated with related drugs for 12 weeks. Body mass, liver wet weight, and liver index were detected. Serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), total cholesterol(TC), triacylglycerol(TG), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), and lipopolysaccharide(LPS)levels were detected using the biochemical kits. The contents of tumor necrosis factor-α(TNF-α) and interleukin(IL-6) in the liver were tested simultaneously. The morphological changes of the liver and intestine were observed using hematoxylin-eosin(HE) staining and oil red O staining. The goblet cells in the ileum were detected by periodic acid Schiff and alcian blue stain(AB-PAS) staining.The expression of zonula occludens-1(ZO-1), recombinant occludin(occludin), and recombinant claudin 1(claudin-1) in ileum and colon were detected by immunohistochemistry and Western blot. The changes of intestinal flora in mice were analyzed by 16S rRNA gene sequencing. The results showed that compared with the normal group, body weight, liver wet weight and liver index in the model group increased. The contents of TC, TG, ALT, AST, LDL-C, and LPS in the serum of the model group increased, while HDL-C decreased. Meanwhile, the contents of TNF-α and IL-6 in liver tissue increased and liver lipid accumulation increased, indicating successful model induction. Compared with the model group, body weight, liver wet weight, and liver index were decreased in XM,XH groups and SQ group. Serum levels of TC, TG, LDL-C, ALT and AST in XM group and SQ group were significantly decreased,and HDL-C levels were increased. The levels of IL-6, TNF-α in liver tissue and serum LPS in the XL, XM groups and SQ group were significantly decreased. The protein expression of claudin-1, occludin and ZO-1 in XL, XM groups and SQ group were increased. The analysis of intestinal flora showed that compared with the model group, Modified Xiaoyao Powder with a medium dose could significantly improve the richness and diversity of intestinal flora in mice. At the phylum level, the Firmicutes/Bacteroidetes(F/B) ratio decreased; at the genus level, Lactobacillus, Brautella, Bacteroides, and Ackermannia increased, while Prevotella, Desulfovibrio and Turicibacter decreased. The main differential species were Odorbacteraceaeae and Peptostreptococcaceae. In conclusion, Modified Xiaoyao Powder could inhibit inflammation, regulate intestinal flora homeostasis, and promote the repair of the intestinal mucosal barrier in mice with MAFLD.

Construction and validation of a nomogram model to predict symptomatic intracranial hemorrhage after intravenous thrombolysis in severe white matter lesions.

Cerebral white matter lesions (WMLs) increase the risk of bleeding after intravenous thrombolysis (IVT) but are also considered to require IVT. Its risk factors and predictive models are still poorly studied. The aim of this study is to develop a clinically applicable model for post-IVT haemorrhage. It offers the possibility to prevent symptomatic intracranial hemorrhage (sICH) in patients with IVT in severe WMLs. A large single-center observational study conducted a retrospective analysis of IVT in patients with severe WMLs from January 2018 to December 2022. Univariate and multi-factor logistic regression results were used to construct nomogram model, and a series of validations were performed on the model. More than 2,000 patients with IVT were screened for inclusion in this study after cranial magnetic resonance imaging evaluation of 180 patients with severe WMLs, 28 of whom developed sICH. In univariate analysis, history of hypertension (OR 3.505 CI 2.257-4.752, p = 0.049), hyperlipidemia (OR 4.622 CI 3.761- 5.483, p < 0.001), the NIHSS score before IVT (OR 41.250 CI 39.212-43.288, p < 0.001), low-density lipoprotein levels (OR 1.995 CI 1.448-2.543, p = 0.013), cholesterol levels (OR 1.668 CI 1.246-2.090, p = 0.017), platelet count (OR 0.992 CI 0.985-0.999, p = 0.028), systolic blood pressure (OR 1.044 CI 1.022-1.066, p < 0.001), diastolic blood pressure (OR 1.047 CI 1.024-1.070, p < 0.001) were significantly associated with sICH. In a multifactorial analysis, the NIHSS score before IVT (OR 94.743 CI 92.311-97.175, p < 0.001), and diastolic blood pressure (OR 1.051 CI 1.005-1.097, p = 0.033) were considered to be significantly associated with sICH after IVT as risk factors for the occurrence of sICH. The four most significant factors from logistic regression are subsequently fitted to create a predictive model. The accuracy was verified using ROC curves, calibration curves, decision curves, and clinical impact curves, and the model was considered to have high accuracy (AUC 0.932, 95% 0.888-0.976). The NHISS score before IVT and diastolic blood pressure are independent risk factors for sICH after IVT in patients with severe WMLs. The models based on hyperlipidemia, the NIHSS score before IVT, low-density lipoprotein and diastolic blood pressure are highly accurate and can be applied clinically to provide a reliable predictive basis for IVT in patients with severe WMLs.

Presence of tannins in sorghum grains is conditioned by different natural alleles of Tannin1.

Sorghum, an ancient old-world cereal grass, is the dietary staple of over 500 million people in more than 30 countries in the tropics and semitropics. Its C4 photosynthesis, drought resistance, wide adaptation, and high nutritional value hold the promise to alleviate hunger in Africa. Not present in other major cereals, such as rice, wheat, and maize, condensed tannins (proanthocyanidins) in the pigmented testa of some sorghum cultivars have been implicated in reducing protein digestibility but recently have been shown to promote human health because of their high antioxidant capacity and ability to fight obesity through reduced digestion. Combining quantitative trait locus mapping, meta-quantitative trait locus fine-mapping, and association mapping, we showed that the nucleotide polymorphisms in the Tan1 gene, coding a WD40 protein, control the tannin biosynthesis in sorghum. A 1-bp G deletion in the coding region, causing a frame shift and a premature stop codon, led to a nonfunctional allele, tan1-a. Likewise, a different 10-bp insertion resulted in a second nonfunctional allele, tan1-b. Transforming the sorghum Tan1 ORF into a nontannin Arabidopsis mutant restored the tannin phenotype. In addition, reduction in nucleotide diversity from wild sorghum accessions to landraces and cultivars was found at the region that codes the highly conserved WD40 repeat domains and the C-terminal region of the protein. Genetic research in crops, coupled with nutritional and medical research, could open the possibility of producing different levels and combinations of phenolic compounds to promote human health.

Causal association between mental disorders and cerebrovascular diseases: Evidence from Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Observational studies have suggested that mental disorders and cerebrovascular diseases (CVDs) may be risk factors for each other, but genetic evidence of a causal relationship is still lacking. We used Mendelian randomization (MR) studies to explore the causal relationship between mental disorders and CVDs from the genetic perspective. METHODS: To investigate the causal association between major depressive disorder (MDD), anxiety, attention deficit/hyperactivity disorder (ADHD), bipolar disorder and schizophrenia five kinds of mental disorders and CVDs using two-sample two-way MR analysis based on publicly available genome-wide association study (GWAS) data. We used as instrumental variables (IVs) single-nucleotide polymorphisms (SNPs) that were strongly associated with mental disorders and CVDs. IVW method was used as the main analysis method, and MR-IVW, MR-Egger methods, MR-PRESSO test, leave-one-out analysis and funnel plot were used for sensitivity analysis. We further conducted a meta-analysis to summarize the currently available MR analyses. RESULTS: The results of forward MR study showed that there was a significant causal relationship between ADHD and AS (any stroke) (p(AS) = 0.001, OR (95%CI) =1.118 (1.047-1.195)), any ischemic stroke (AIS) (p(AIS) = 0.004, OR (95%CI) =1.118(1.035-1.206)) and large artery stroke (LAS) (p(LAS) = 0.026, OR (95%CI): 1.206(1.023-1.422)). No heterogeneity, pleiotropy and outliers were found in sensitivity analysis. The reverse MR study showed that IA (intracranial aneurysm) (p(IA) = 0.033, OR (95%CI) = 1.123(1.009-1.249)) and UIA (unruptured intracranial aneurysm) (p(UIA) = 0.015, OR (95%CI) =1.040(1.008-1.074)) were risk factors for schizophrenia. Sensitivity analysis showed no pleiotropy, but there was heterogeneity. After excluding outliers, MR analysis showed that IA and UIA were still risk factors for schizophrenia. Our meta-analyses found statistical significance in causal relationships between ADHD and LAS (OR (95%CI) =1.18 (1.06-1.32), p = 0.003), IA and schizophrenia (OR (95%CI) =1.05 (1.02-1.08), p = 0.002) and UIA and schizophrenia (OR (95%CI) =1.03 (1.01-1.06), p = 0.010). CONCLUSION: The MR study and meta-analysis suggest that genetically predicted ADHD is a risk factor for LAS, and IA and UIA increase the risk of schizophrenia. The result has implications for the development of feasible prevention strategies in the future.

Causal relationship between sleep disorders and the risk of Alzheimer's disease: A Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Epidemiological studies have shown that sleep disorders are risk factors for Alzheimer's disease (AD), but the causal relationship between sleep disorders and AD risk is unknown. We aim to assess the potential genetic causal association between sleep characteristics and AD, which may contribute to early identification and prediction of risk factors for AD. METHODS: Seven sleep-related traits and the outcome phenotype AD were selected from published genome-wide association studies (GWASs). These sleep-related characteristics and instrumental variables (IVs) for AD were extracted. Two-sample and multivariate Mendelian randomization (MR) analyses were performed to assess the causal relationships between sleep characteristics and AD. The inverse variance weighted (IVW), weighted median (WME), weighted mode (WM), MR-Egger regression (MR-Egger) and simple mode (SM) models were used to evaluate causality. The existence of pleiotropy was detected and corrected by MR-Egger regression, MR pleiotropy residuals and outliers. RESULTS: A two-sample MR study revealed a positive causal association between sleep duration and the onset of AD (OR = 1.002, 95 % CI: 1.000-1.004), and the risk of AD increased with increasing sleep duration. The MR-Egger regression method and MR-PRESSO were used to identify and correct pleiotropy, indicating that there was no horizontal pleiotropy. Heterogeneity was evaluated by Cochran's Q, which indicated no heterogeneity. In a multivariate MR study with seven sleep characteristics corrected for each other, we found that sleep duration remained causally associated with AD (OR = 1.004, 95 % CI: 1.000-1.007). Moreover, we found that after mutual correction, daytime napping had a causal relationship with the onset of AD, and daytime napping may reduce the risk of AD (OR = 0.995, 95 % CI: 0.991-1.000). CONCLUSION: This study is helpful for the early identification and prediction of risk factors for AD, long sleep durations are a risk factor for AD, and daytime napping can reduce the risk of AD.

Trans-nuclease activity of Cas9 activated by DNA or RNA target binding.

Type V and type VI CRISPR-Cas systems have been shown to cleave nonspecific single-stranded DNA (ssDNA) or single-stranded RNA (ssRNA) in trans, but this has not been observed in type II CRISPR-Cas systems using single guide RNA. We show here that the type II CRISPR-Cas9 systems directed by CRISPR RNA and trans-activating CRISPR RNA dual RNAs show RuvC domain-dependent trans-cleavage activity for both ssDNA and ssRNA substrates. Cas9 possesses sequence preferences for trans-cleavage substrates, preferring to cleave T- or C-rich ssDNA substrates. We find that the trans-cleavage activity of Cas9 can be activated by target ssDNA, double-stranded DNA and ssRNA. The crystal structure of Cas9 in complex with guide RNA and target RNA provides a structural basis for the binding of target RNA to activate Cas9. Based on the trans-cleavage activity of Cas9 and nucleic acid amplification technology, we develop the nucleic acid detection platforms DNA-activated Cas9 detection and RNA-activated Cas9 detection, which are capable of detecting DNA and RNA samples with high sensitivity and specificity.

Dentatorubral-pallidoluysian atrophy: a case report and review of literature.

BACKGROUND: Dentatorubral-pallidoluysian atrophy is a rare autosomal dominant neurodegenerative disease. It is a rare disease in the world. Therefore, sharing clinical encounters of this case can deepen global awareness and understanding of the disease. CASE PRESENTATION: The patient was a 34-year-old male of Han nationality who was unmarried. The patient was admitted owing to weakness of the left lower limb with walking instability for 2 months and aggravation for 1 month. There was no dizziness, headache, numbness of limbs, convulsions, nausea, vomiting, abdominal pain, ataxia, nausea, vomiting, or abdominal pain. No nausea, vomiting, diarrhea, abdominal distension, tinnitus, hearing loss, fever, cough, expectoration. Personal history: worked in Cambodia 5 years ago, worked in Dubai 3 years ago, engaged in computer work, smoking or drinking habits. The patient was unmarried. Family history: the mother had symptoms similar to walking unsteadily (undiagnosed). Positive signs include a wide-base gait with a rotatory nystagmus that jumps upward in both eyes. Bilateral finger-nose instability test was quasi-positive, rapid alternating test was negative, and eye closure tolerance test was positive. Tendon reflexes were active in both upper limbs and hyperreflexia in both lower limbs. Stability of the heel, knee, and tibia. Genetic testing showed that the number of repeats in the dentatorubral-pallidoluysian atrophy ATN1 gene was 18 and 62, and the (CAG)n repeat sequence in the ATN1 gene was abnormal, with a repeat number of 62, and the patient was a pathogenic variant. The patient was diagnosed with dentatorubral-pallidoluysian atrophy. Dentatorubral-pallidoluysian atrophy remains a progressive neurodegenerative disease with no effective treatment. At present, the proband is taking 5 mg of buspirone three times a day, which has been reported to improve the symptoms. The patient was followed up for 6 months after taking buspirone, and there was no significant improvement in the temporary symptoms. At present, there are few cases of dentatorubral-pallidoluysian atrophy, and the characteristics of nystagmus in this disease have not been proposed in the past. This case reported the unusual presentation of nystagmus. CONCLUSION: Dentatorubral-pallidoluygur atrophy is a rare neurodegenerative disease with autosomal dominant inheritance. To the best of our knowledge, our present case report is the first case report of dentatorubral-pallidoluygur atrophy with specific nystagmus. We describe the special eye shake and its positive signs to increase dentatorubral-pallidoluysian atrophy clinical positive signs.

Comparative mapping in watermelon [Citrullus lanatus (Thunb.) Matsum. et Nakai].

The first single-nucleotide polymorphism (SNP) maps for watermelon [Citrullus lanatus (Thunb.) Matsum. et Nakai] were constructed and compared. Three populations were developed from crosses between two elite cultivars, Klondike Black Seeded × New Hampshire Midget (KBS × NHM), an elite cultivar and wild egusi accession, Strain II × PI 560023 (SII × Egusi) and an elite cultivar and a wild citron accession, ZWRM50 × PI 244019 (ZWRM × Citroides). The SII × Egusi and ZWRM × Citroides F(2) populations consisted of 187 and 182 individuals respectively while the KBS × NHM recombinant inbred line (RIL) population consisted of 164 lines. The length of the genetic maps were 1,438, 1,514 and 1,144 cM with average marker distances of 3.8, 4.2, and 3.4 cM for the KBS × NHM, SII × Egusi and ZWRM × Citroides populations, respectively. Shared markers were used to align the three maps so that the linkage groups (LGs) represented the 11 chromosomes of the species. Marker segregation distortion were observed in all three populations, but was highest (12.7 %) in the ZWRM × Citroides population, where Citroides alleles were favored. The three maps were used to construct a consensus map containing 378 SNP markers with an average distance of 5.1 cM between markers. Phenotypic data was collected for fruit weight (FWT), fruit length (FL), fruit width (FWD), fruit shape index (FSI), rind thickness (RTH) and Brix (BRX) and analyzed for quantitative trait loci (QTL) associated with these traits. A total of 40 QTL were identified in the three populations, including major QTL for fruit size and shape that were stable across genetic backgrounds and environments. The present study reports the first SNP maps for Citrullus and the first map constructed using two elite parents. We also report the first stable QTL associated with fruit size and shape in Citrullus lanatus. These maps, QTL and SNPs should be useful for the watermelon community and represent a significant step towards the potential use of molecular tools in watermelon breeding.

Structural basis for MTA1c-mediated DNA N6-adenine methylation.

DNA N6-adenine methylation (6 mA) has recently been found to play a crucial role in epigenetic regulation in eukaryotes. MTA1c, a newly discovered 6 mA methyltransferase complex in ciliates, is composed of MTA1, MTA9, p1 and p2 subunits and specifically methylates ApT dinucleotides, yet its mechanism of action remains unknown. Here, we report the structures of Tetrahymena thermophila MTA1 (TthMTA1), Paramecium tetraurelia MTA9 (PteMTA9)-TthMTA1 binary complex, as well as the structures of TthMTA1-p1-p2 and TthMTA1-p2 complexes in apo, S-adenosyl methionine-bound and S-adenosyl homocysteine-bound states. We show that MTA1 is the catalytically active subunit, p1 and p2 are involved in the formation of substrate DNA-binding channel, and MTA9 plays a structural role in the stabilization of substrate binding. We identify that MTA1 is a cofactor-dependent catalytically active subunit, which exhibits stable SAM-binding activity only after assembly with p2. Our structures and corresponding functional studies provide a more detailed mechanistic understanding of 6 mA methylation.

Aptamer-based biosensor for detecting carcinoembryonic antigen.

Carcinoembryonic antigen (CEA), as one of the common tumor markers, is a human glycoprotein involved in cell adhesion and is expressed during human fetal development. Since the birth of human, CEA expression is largely inhibited, with only low levels in the plasma of healthy adults. Generally, CEA will overexpressed in many cancers, including gastric, breast, ovarian, lung, and pancreatic cancers, especially colorectal cancer. As one of the important tumor markers, the detection of CEA has great significance in differential diagnosis, condition monitoring and therapeutic evaluation of diseases. Conventional CEA testing typically uses immunoassay methods. However, immunoassay methods require complex and expensive instruments and professional personnel to operate. Moreover, radioactive element may cause certain damage to the human body, which limits their wide application. In the past few years, biosensors, especially aptamer-based biosensors, have attracted extensive attention due to their high sensitivity, good selectivity, high accuracy, fast response and low cost. This review briefly classifies and describes the advance in optical and electrochemical aptamer biosensors for CEA detection, also explains and compares their advantages and disadvantages.

Cocaine detection using aptamer and molybdenum disulfide-gold nanoparticle-based sensors.

Aim: The current work highlighted a novel colorimetric sensor based on aptamer and molybdenum disulfide (MoS2)-gold nanoparticles (AuNPs) that was developed for cocaine detection with high sensitivity. Materials & methods: Due to the presence of the plasmon resonance band on the surface of AuNPs, AuNPs aggregated and the color was changed from red to blue after adding a certain concentration of NaCl. We used MoS2 to optimize the sensing system of AuNPs. The folded conformation of the aptamer in combination with cocaine enhanced the salt tolerance of the MoS2-AuNPs, effectively preventing their aggregation. Results & conclusion: The detection limit of cocaine was 7.49 nM with good selectivity. The method based on MoS2-AuNPs colorimetry sensor is simple, quick, label-free and low cost.

Highly sensitive detection of carcinoembryonic antigen using copper-free click chemistry on the surface of azide cofunctionalized graphene oxide.

In this study, we reported a highly sensitive method for detecting carcinoembryonic antigen (CEA) based on an azide cofunctionalized graphene oxide (GO-N3) and carbon dot (CDs) biosensor system. Carbon dots-labeled DNA (CDs-DNA) combined with GO-N3 using copper-free click chemistry (CFCC), which quenched the fluorescence of the CDs via fluorescence resonance energy transfer (FRET). Upon the addition of CEA, fluorescence was recovered due to the combination of CEA and aptamer. Under optimal conditions, the relative fluorescence intensity was linear with CEA concentration in the range of 0.01-1 ng/mL (R2 = 0.9788), and the limit of detection (LOD) was 7.32 pg/mL (S/N = 3). This biosensor had a high sensitivity and good selectivity for CEA detection in serum samples, indicating that the novel sensor platform holds a great potential for CEA and other biomarkers in practical applications.

The detection of mercury ion using DNA as sensors based on fluorescence resonance energy transfer.

Mercury ion (Hg2+) is a heavy metal that can cause serious water pollution. With the accumulation of large quantities in lakes, rivers, freshwater and aquatic life, Hg2+ can pass through the food chain, entering the human body and endangering health. Hg2+ detection has therefore become important thereby attracting extensive interests. Currently, several DNA-based sensors have been used for Hg2+ detection because they are not easy to degrade and are very stable. This paper summarizes the application of some DNA-based sensors based on fluorescence resonance energy transfer (FRET), analyzes their characteristic, and compares their sensitivity. Future perspectives and possible challenges in this area are also outlined.