An additional proofreader contributes to DNA replication fidelity in mycobacteria.

The removal of mis-incorporated nucleotides by proofreading activity ensures DNA replication fidelity. Whereas the ε-exonuclease DnaQ is a well-established proofreader in the model organism Escherichia coli, it has been shown that proofreading in a majority of bacteria relies on the polymerase and histidinol phosphatase (PHP) domain of replicative polymerase, despite the presence of a DnaQ homolog that is structurally and functionally distinct from E. coli DnaQ. However, the biological functions of this type of noncanonical DnaQ remain unclear. Here, we provide independent evidence that noncanonical DnaQ functions as an additional proofreader for mycobacteria. Using the mutation accumulation assay in combination with whole-genome sequencing, we showed that depletion of DnaQ in Mycolicibacterium smegmatis leads to an increased mutation rate, resulting in AT-biased mutagenesis and increased insertions/deletions in the homopolymer tract. Our results showed that mycobacterial DnaQ binds to the ß clamp and functions synergistically with the PHP domain proofreader to correct replication errors. Furthermore, the loss of dnaQ results in replication fork dysfunction, leading to attenuated growth and increased mutagenesis on subinhibitory fluoroquinolones potentially due to increased vulnerability to fork collapse. By analyzing the sequence polymorphism of dnaQ in clinical isolates of Mycobacterium tuberculosis (Mtb), we demonstrated that a naturally evolved DnaQ variant prevalent in Mtb lineage 4.3 may enable hypermutability and is associated with drug resistance. These results establish a coproofreading model and suggest a division of labor between DnaQ and PHP domain proofreader. This study also provides real-world evidence that a mutator-driven evolutionary pathway may exist during the adaptation of Mtb.

Identification of functional circRNAs regulating ovarian follicle development in goats.

BARKGROUND: Circular RNAs (circRNAs) play important regulatory roles in a variety of biological processes in mammals. Multiple birth-traits in goats are affected by several factors, but the expression and function of circRNAs in follicular development of goats are not clear. In this study, we aimed to investigate the possible regulatory mechanisms of circRNA and collected five groups of large follicles (Follicle diameter > 6 mm) and small follicles (1 mm < Follicle diameter < 3 mm) from Leizhou goats in estrus for RNA sequencing. RESULTS: RNA sequencing showed that 152 circRNAs were differentially expressed in small and large follicles. Among them, 101 circRNAs were up-regulated in large follicles and 51 circRNAs were up-regulated in small follicles. GO and KEGG enrichment analyses showed that parental genes of the differential circRNAs were significantly enriched in important pathways, such as ovarian steroidogenesis, GnRH signaling pathway, animal autophagy and oxytocin signalling pathway. BioSignal analysis revealed that 152 differentially expressed circRNAs could target 91 differential miRNAs including miR-101 family (chi-miR-101-3p, chi-miR-101-5p), miR-202 family (chi-miR-202-5p, chi-miR-202-3p),60 circRNAs with translation potential. Based on the predicted sequencing results, the ceRNA networks chicirc_008762/chi-miR-338-3p/ARHGAP18 and chicirc_040444/chi-miR-338-3p/STAR were constructed in this study. Importantly, the new gene circCFAP20DC was first discovered in goats. The EDU assay and flow cytometry results indicated that circCFAP20DC enhanced the proliferation of follicular granulosa cells(GCs). Real-time quantitative PCR and western blotting assays showed that circCFAP20DC activated the Retinoblastoma(RB) pathway and promoted the progression of granulosa cells from G1 to S phase. CONCLUSION: Differential circRNAs in goat size follicles may have important biological functions for follicular development. The novel gene circCFAP20DC activates the RB pathway, promoting the progression of GCs from G1 to S phase. This, in turn, enhances the proliferation of follicular GCs in goats.

Maternal history of Alzheimer's disease predisposes to altered serum cholesterol levels in adult offspring.

Controversial findings regarding the association between serum cholesterol levels and Alzheimer's disease (AD) have been identified through observational studies. The genetic basis shared by both factors and the causality between them remain largely unknown. The objective of this study is to examine the causal impact of maternal history of AD on changes in serum cholesterol levels in adult offspring. By retrieving genetic variants from summary statistics of large-scale genome-wide association study of maternal history of AD (European-based: Ncase = 27 696, Ncontrol = 260 980). The causal association between genetically predicted maternal history of AD and changes in serum cholesterol levels in adult offspring was examined using the two-sample Mendelian randomization (MR) method. Causal impact estimates were calculated using single-nucleotide polymorphisms in both univariable MR (UMR) and multivariable MR (MVMR) analyses. Additionally, other approaches, such as Cochran's Q test and leave-one-out variant analysis, were employed to correct for potential biases. The results of UMR presented that genetically predicted maternal history of AD was positively associated with hypercholesterolemia (OR = 1.014; 95% CI: 1.009-1.018; p < 0.001), total cholesterol (OR = 1.29; 95% CI: 1.134-1.466; p < 0.001) and low-density lipoprotein (OR = 1.525; 95% CI: 1.272-1.828; p < 0.001) among adult offspring. Genetic predisposition for maternal history of AD to be negatively associated with high-density lipoprotein (OR = 0.889; 95% CI: 0.861-0.917; p < 0.001). The MVMR analysis remained robust and significant after adjusting for diabetes and obesity in offspring. Sufficient evidence was provided in this study to support the putative causal impact of maternal history of AD on the change of serum cholesterol profile in adult offspring. In clinical practice, priority should be given to the detection and monitoring of cholesterol levels in individuals with a maternal history of AD, particularly in the early stages.

Multi-omics analysis uncovered systemic lupus erythematosus and COVID-19 crosstalk.

BACKGROUND: Studies have highlighted a possible crosstalk between the pathogeneses of COVID-19 and systemic lupus erythematosus (SLE); however, the interactive mechanisms remain unclear. We aimed to elucidate the impact of COVID-19 on SLE using clinical information and the underlying mechanisms of both diseases. METHODS: RNA-seq datasets were used to identify shared hub gene signatures between COVID-19 and SLE, while genome-wide association study datasets were used to delineate the interaction mechanisms of the key signaling pathways. Finally, single-cell RNA-seq datasets were used to determine the primary target cells expressing the shared hub genes and key signaling pathways. RESULTS: COVID-19 may affect patients with SLE through hematologic involvement and exacerbated inflammatory responses. We identified 14 shared hub genes between COVID-19 and SLE that were significantly associated with interferon (IFN)-I/II. We also screened and obtained four core transcription factors related to these hub genes, confirming the regulatory role of the IFN-I/II-mediated Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway on these hub genes. Further, SLE and COVID-19 can interact via IFN-I/II and IFN-I/II receptors, promoting the levels of monokines, including interleukin (IL)-6/10, tumor necrosis factor-α, and IFN-γ, and elevating the incidence rate and risk of cytokine release syndrome. Therefore, in SLE and COVID-19, both hub genes and core TFs are enriched within monocytes/macrophages. CONCLUSIONS: The interaction between SLE and COVID-19 promotes the activation of the IFN-I/II-triggered JAK-STAT signaling pathway in monocytes/macrophages. These findings provide a new direction and rationale for diagnosing and treating patients with SLE-COVID-19 comorbidity.

Toxoplasma gondii Induces Pyroptosis in Human Placental Trophoblast and Amniotic Cells by Inducing ROS Production and Activation of Cathepsin B and NLRP1/NLRP3/NLRC4/AIM2 Inflammasome.

Toxoplasma gondii infection in pregnant women may cause fetal anomalies; however, the underlying mechanisms remain unclear. The current study investigated whether T. gondii induces pyroptosis in human placental cells and the underlying mechanisms. Human placental trophoblast (BeWo and HTR-8/SVneo) and amniotic (WISH) cells were infected with T. gondii, and then reactive oxygen species (ROS) production, cathepsin B (CatB) release, inflammasome activation, and pyroptosis induction were evaluated. The molecular mechanisms of these effects were investigated by treating the cells with ROS scavengers, a CatB inhibitor, or inflammasome-specific siRNA. T. gondii infection induced ROS generation and CatB release into the cytosol in placental cells but decreased mitochondrial membrane potential. T. gondii-infected human placental cells and villi exhibited NLRP1, NLRP3, NLRC4, and AIM2 inflammasome activation and subsequent pyroptosis induction, as evidenced by increased expression of ASC, cleaved caspase-1, and mature IL-1ß and gasdermin D cleavage. In addition to inflammasome activation and pyroptosis induction, adverse pregnancy outcome was shown in a T. gondii-infected pregnant mouse model. Administration of ROS scavengers, CatB inhibitor, or inflammasome-specific siRNA into T. gondii-infected cells reversed these effects. Collectively, these findings show that T. gondii induces NLRP1/NLRP3/NLRC4/AIM2 inflammasome-dependent caspase-1-mediated pyroptosis via induction of ROS production and CatB activation in placental cells. This mechanism may play an important role in inducing cell injury in congenital toxoplasmosis.

Experimental study of modified Tavis-Cummings model with directly-coupled superconducting artificial atoms.

The Tavis-Cummings model is intensively investigated in quantum optics and has important applications in generation of multi-atom entanglement. Here, we employ a superconducting circuit quantum electrodynamic system to study a modified Tavis-Cummings model with directly-coupled atoms. In our device, three superconducting artificial atoms are arranged in a chain with direct coupling through fixed capacitors and strongly coupled to a transmission line resonator. By performing transmission spectrum measurements, we observe different anticrossing structures when one or two qubits are resonantly coupled to the resonator. In the case of the two-qubit Tavis-Cummings model without qubit-qubit interaction, we observe two dips at the resonance point of the anticrossing. The splitting of these dips is determined by Δ λ=2g12+g32, where g1 and g3 are the coupling strengths between Qubit 1 and the resonator, and Qubit 3 and the resonator, respectively. The direct coupling J12 between the two qubits results in three dressed states in the two-qubit Tavis-Cummings model at the frequency resonance point, leading to three dips in the transmission spectrum. In this case, the distance between the two farthest and asymmetrical dips, arising from the energy level splitting, is larger than in the previous case. The frequency interval between these two dips is determined by the difference in eigenvalues (Δ λ=ε 1+-ε 1-), obtained through numerical calculations. What we believe as novel and intriguing experimental results may potentially advance quantum optics experiments, providing valuable insights for future research.

RNA epigenetic modifications in digestive tract cancers: Friends or foes.

Digestive tract cancers are among the most common malignancies worldwide and have high incidence and mortality rates. Thus, the discovery of more effective diagnostic and therapeutic targets is urgently required. The development of technologies to accurately detect RNA modification has led to the identification of numerous RNA chemical modifications in humans (epitranscriptomics) that are involved in the occurrence and development of digestive tract cancers. RNA modifications can cooperatively regulate gene expression to facilitate normal physiological functions of the digestive system. However, the dysfunction of relevant RNA-modifying enzymes ("writers," "erasers," and "readers") can lead to the development of digestive tract cancers. Consequently, targeting dysregulated enzyme activity could represent a potent therapeutic strategy for the treatment of digestive tract cancers. In this review, we summarize the most widely studied roles and mechanisms of RNA modifications (m6A, m1A, m5C, m7G, A-to-I editing, pseudouridine [Ψ]) in relation to digestive tract cancers, highlight the crosstalk between RNA modifications, and discuss their roles in the interactions between the digestive system and microbiota during carcinogenesis. The clinical significance of novel therapeutic methods based on RNA-modifying enzymes is also discussed. This review will help guide future research into digestive tract cancers that are resistant to current therapeutics.

Preparation of Indolin-3-one-Containing 1,4-Naphthoquinone Derivatives via Organocatalytic Asymmetric Michael Addition Reaction.

This article explores the asymmetric Michael addition reaction of 2-hydroxy-1,4-naphthoquinone and indole-3-ones catalyzed by cinchona alkaloids. This strategy utilizes 2-hydroxy-1,4-naphthoquinone and easily prepared indole-3-one as substrates, resulting in the synthesis of 23 unprecedented indolin-3-ones bearing a 1,4-naphthoquinone unit at the C2 position of indole under simple and mild reaction conditions, with up to 88% yield, 98% ee, and >20:1 dr.

Retrospective assessment of short-term outcomes of robotic- versus laparoscopic-assisted duodenal diamond anastomosis in neonates.

OBJECTIVE: The purpose of this study was to retrospectively compare the short-term outcomes of robotic- (RAD) and laparoscopic-assisted duodenal diamond-shaped anastomosis (LAD) in neonates. METHODS: Neonates who underwent RAD (n = 30) or LAD (n = 38) between January 2019 and December 2022 were analyzed retrospectively. Major patient data were collected, including preoperative, intraoperative, and postoperative information. RESULTS: All patients were neonates below the age of 30 days weighing 4 kg. Thirty (44.1%) neonates underwent RAD and 38 neonates (55.9%) underwent LAD. Compared to the LAD group, the RAD group had a shorter intra-abdominal operation time (RAD, 60.0(50.0 ~ 70.0) min; LAD, 79.9(69.0 ~ 95.3) min; p < 0.001). There were no significant differences in immediate and 30-day complications between the two groups. CONCLUSIONS: RAD is safe and effective in neonates. Compared to traditional LAD, RAD showed comparable results.

Development of platensimycin, platencin, and platensilin overproducers by biosynthetic pathway engineering and fermentation medium optimization.

The platensimycin (PTM), platencin (PTN), and platensilin (PTL) family of natural products continues to inspire the discovery of new chemistry, enzymology, and medicine. Engineered production of this emerging family of natural products, however, remains laborious due to the lack of practical systems to manipulate their biosynthesis in the native-producing Streptomyces platensis species. Here we report solving this technology gap by implementing a CRISPR-Cas9 system in S. platensis CB00739 to develop an expedient method to manipulate the PTM, PTN, and PTL biosynthetic machinery in vivo. We showcase the utility of this technology by constructing designer recombinant strains S. platensis SB12051, SB12052, and SB12053, which, upon fermentation in the optimized PTM-MS medium, produced PTM, PTN, and PTL with the highest titers at 836 mg L-1, 791 mg L-1, and 40 mg L-1, respectively. Comparative analysis of these resultant recombinant strains also revealed distinct chemistries, catalyzed by PtmT1 and PtmT3, two diterpene synthases that nature has evolved for PTM, PTN, and PTL biosynthesis. The ΔptmR1/ΔptmT1/ΔptmT3 triple mutant strain S. platensis SB12054 could be envisaged as a platform strain to engineer diterpenoid biosynthesis by introducing varying ent-copalyl diphosphate-acting diterpene synthases, taking advantage of its clean metabolite background, ability to support diterpene biosynthesis in high titers, and the promiscuous tailoring biosynthetic machinery. ONE-SENTENCE SUMMARY: Implementation of a CRISPR-Cas9 system in Streptomyces platensis CB00739 enabled the construction of a suite of designer recombinant strains for the overproduction of platensimycin, platencin, and platensilin, discovery of new diterpene synthase chemistries, and development of platform strains for future diterpenoid biosynthesis engineering.

Genome-wide identification of G-protein coupled receptors (GPCRs) and their expression profile in response to ß-cypermethrin stress in Zeugodacus cucurbitae.

G-protein coupled receptors (GPCRs) are the largest and most diverse transmembrane receptor family in the cell. They are involved in regulating a wide range of biological processes, including behavior, reproduction, and development. However, GPCRs have not yet been identified in Zeugodacus cucurbitae. The current study focuses on the GPCRs identification, classification, distribution, and their expression analysis under ß-cypermethrin stress to uncover novel targets for pest management and assist in the development of effective strategies for controlling the melon fly population. We identified 80 GPCRs genes including 50 GPCRs identified in family A, 17 GPCRs identified in family B, 8 identified in family C, and 5 identified in family F. Z. cucurbitae GPCRs showed significant differences in both the number of genes in families or subfamilies, as well as the sequencing of the genes. Interestingly, newly identified GPCRs genes are expressed differently at various developmental stages of Z. cucurbitae. Further, we evaluated these 80 GPCRs using Realtime quantitative PCR to confirm their expression between ß-cypermethrin-resistant (RS) strain and susceptible strain (SS) of Z. cucurbitae. We identified 50 GPCR genes were highly overexpressed in a RS. Among these genes, eight genes were strongly induced by the 30% lethal concentration (LC) while two genes were significantly increased by the 50% LC of ß-cypermethrin. This first genome-wide profiling and characterization of GPCRs could lay foundation for unraveling detoxification mechanism and target site modifications which may improve the insect resistance and could be effective insecticide targets for Z. cucurbitae management.

Identification and Functional Analysis of circRNAs during Goat Follicular Development.

Litter size is a crucial quantitative trait in animals, closely linked to follicular development. Circular RNA (circRNA), a type of single-stranded closed-loop endogenous RNA with stable expression, plays pivotal roles in various biological processes, yet its function in goat follicular development remains unclear. In this study, we collected large (follicle diameter > 3 mm) and small (1 mm < follicle diameter < 3 mm) follicles from black goats in the Chuanzhong region for circRNA sequencing, with the aim of elucidating the functional circRNAs that influence follicle development in goats. Differential analysis revealed that 17 circRNAs were upregulated in large follicles, and 28 circRNAs were upregulated in small follicles. Functional enrichment analysis revealed significant enrichment of pathways related to reproduction, including cellular response to follicle-stimulating hormone stimulus, the PI3K-Akt signaling pathway, the MAPK signaling pathway, and the Notch signaling pathway. Based on the ceRNA mechanism, 45 differentially expressed circRNAs were found to target and bind a total of 418 miRNAs, and an intercalation network including miR-324-3p (circRNA2497, circRNA5650), miR-202-5p (circRNA3333, circRNA5501), and miR-493-3p (circRNA4995, circRNA5508) was constructed. In addition, conservation analysis revealed that 2,239 circRNAs were conserved between goats and humans. Prediction of translation potential revealed that 154 circRNAs may potentially utilize both N6-methyladenosine (m6A) and internal ribosome entry site (IRES) translation mechanisms. Furthermore, the differential expression and circularization cleavage sites of five circRNAs were validated through RT-qPCR and DNA sequencing. Our study constructed a circRNA map in goat follicle development, offering a theoretical foundation for enhancing goat reproductive performance.

miR-128-3p Regulates Follicular Granulosa Cell Proliferation and Apoptosis by Targeting the Growth Hormone Secretagogue Receptor.

The proliferation and apoptosis of granulosa cells (GCs) affect follicle development and reproductive disorders, with microRNAs playing a crucial regulatory role. Previous studies have shown the differential expression of miR-128-3p at different stages of goat follicle development, which suggests its potential regulatory role in follicle development. In this study, through the Cell Counting Kit-8 assay, the EDU assay, flow cytometry, quantitative real-time polymerase chain reaction, Western blot, and the dual-luciferase reporter assay, we used immortal human ovarian granulosa tumor cell line (KGN) cells as materials to investigate the effects of miR-128-3p and its predicted target gene growth hormone secretagogue receptor (GHSR) on GC proliferation and apoptosis. The results show that overexpression of miR-128-3p inhibited the proliferation of KGN cells, promoted cell apoptosis, and suppressed the expression of proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2 (BCL2) while promoting that of Bcl-2 associated X protein (BAX). The dual-luciferase reporter assay revealed that miR-128-3p bound to the 3' untranslated region sequence of GHSR, which resulted in the inhibited expression of GHSR protein. Investigation of the effects of GHSR on GC proliferation and apoptosis revealed that GHSR overexpression promoted the expression of PCNA and BCL2, enhanced GC proliferation, and inhibited cell apoptosis, whereas the opposite effects were observed when GHSR expression was inhibited. In addition, miR-128-3p and GHSR can influence the expression of extracellular signal-regulated kinase 1/2 protein. In conclusion, miR-128-3p inhibits KGN cell proliferation and promotes cell apoptosis by downregulating the expression of the GHSR gene.

Expression profile and bioinformatics analysis of circRNA and its associated ceRNA networks in longissimus dorsi from Lufeng cattle and Leiqiong cattle.

This paper aims to explore the role of circRNA expression profiles and circRNA-associated ceRNA networks in the regulation of myogenesis in the longissimus dorsi of cattle breeds surviving under subtropical conditions in southern China by RNA sequencing and bioinformatics analysis. It also aims to provide comprehensive understanding of the differences in muscle fibers in subtropical cattle breeds and to expand the knowledge of the molecular networks that regulate myogenesis. With regard to meat quality indicators, results showed that the longissimus dorsi of LQC had lower pH (P < 0.0001), lower redness (P < 0.01), lower shear force (P < 0.05), and higher brightness (P < 0.05) than the longissimus dorsi of LFC. With regard to muscle fiber characteristics, the longissimus dorsi of LQC had a smaller diameter (P < 0.0001) and higher density of muscle fibers (P < 0.05). The analysis results show that the function of many circRNA-targeted mRNAs was related to myogenesis and metabolic regulation. Furthermore, in the analysis of the function of circRNA source genes, we hypothesized that btacirc_00497 and btacirc_034497 may regulate the function and type of myofibrils by affecting the expression of MYH6, MYH7, and NEB through competitive linear splicing.

Optical fiber strain sensor with high precision and extended dynamic range based on a coupled optoelectronic oscillator.

We have proposed and experimentally demonstrated an optical fiber strain sensor with high precision and extended dynamic range based on a coupled optoelectronic oscillator (COEO). The COEO is a combination of an OEO and a mode-locked laser, sharing one optoelectronic modulator. The feedback between the two active loops makes the oscillation frequency equal to the mode spacing of the laser. It is equivalent to a multiple of the natural mode spacing of the laser, which is affected by the applied axial strain to the cavity. Therefore, we can evaluate the strain by measuring the oscillation frequency shift. Higher sensitivity can be obtained by adopting higher frequency order harmonics owing to the accumulative effect. We carry out a proof-to-concept experiment. The dynamic range can reach 10000 µ ε. Sensitivities of 6.5 Hz/µ ε for 960 MHz and 13.8 Hz/µ ε for 2700 MHz are obtained. The maximum frequency drifts of the COEO in 90 mins are within ±148.03 Hz for 960 MHz and ±303.907 Hz for 2700 MHz, which correspond to measurement errors of ±22 µ ε and ±20 µ ε. The proposed scheme has the advantages of high precision and high speed. The COEO can generate an optical pulse whose pulse period is influenced by the strain. Therefore, the proposed scheme has potential applications in dynamic strain measurement.

Uric acid metabolism promotes apoptosis against Bombyx mori nucleopolyhedrovirus in silkworm, Bombyx mori.

The white epidermis of silkworms is due to the accumulation of uric acid crystals. Abnormal silkworm uric acid metabolism decreases uric acid production, leading to a transparent or translucent phenotype. The oily silkworm op50 is a mutant strain with a highly transparent epidermis derived from the p50 strain. It shows more susceptibility to Bombyx mori nucleopolyhedrovirus (BmNPV) infection than the wild type; however, the underlying mechanism is unknown. This study analysed the changes in 34 metabolites in p50 and op50 at different times following BmNPV infection based on comparative metabolomics. The differential metabolites were mainly clustered in six metabolic pathways. Of these, the uric acid pathway was identified as critical for resistance in silkworms, as feeding with inosine significantly enhanced larval resistance compared to other metabolites and modulated other metabolic pathways. Additionally, the increased level of resistance to BmNPV in inosine-fed silkworms was associated with the regulation of apoptosis, which is mediated by the reactive oxygen species produced during uric acid synthesis. Furthermore, feeding the industrial strain Jingsong (JS) with inosine significantly increased the level of larval resistance to BmNPV, indicating its potential application in controlling the virus in sericulture. These results lay the foundation for clarifying the resistance mechanism of silkworms to BmNPV and provide new strategies and methods for the biological control of pests.

Highly sensitive torsion sensor based on a coupled optoelectronic oscillator incorporating nonlinear polarization rotation.

We propose and demonstrate a new, to the best of our knowledge, technique to implement a high-speed and highly sensitive torsion sensor based on a coupled optoelectronic oscillator (COEO) incorporating nonlinear polarization rotation (NPR). The COEO consists of a mode-locked laser loop and an OEO loop. In the laser loop, the NPR effect effectively induces intensity- and wavelength-dependent loss, which acts as a Lyot birefringent fiber filter. When twisting the polarization-maintaining fiber (PMF), the transmission of the filter varies as well as the laser output wavelength. In the OEO loop, the optical source is provided by the output signal of the mode-locked laser. The variation in the optical carrier wavelength changes the time delay and the oscillation frequency of the OEO loop. The oscillation frequency shift is a linear function of the twist angle. Sensitivities of -60.006 Hz/deg over 360° for a 48 cm PMF and -180.996 Hz/deg over 92° for a 22 cm PMF are achieved.

Predictive value of D-dimer and fibrinogen degradation product for splanchnic vein thrombosis in patients with severe acute pancreatitis: a single-center retrospective study.

BACKGROUND AND AIM: Early diagnosis of splanchnic vein thrombosis (SVT) after severe acute pancreatitis (SAP) remains difficult because of its insidious onset. Common serum markers for thrombosis such as D-dimer (D-D) have lost their diagnostic value due to their elevation in non-thrombotic patients with SAP. The aim of this study is to predict SVT after SAP using common serum indicators of thrombosis by establishing a new cut-off value. METHODS: 177 SAP patients were included in a retrospective cohort study from September 2019 to September 2021. Patient demographics, dynamic changes of coagulation and fibrinolysis indicators were collected. Univariate analyses and binary logistic regression analyses were applied to assess potential risk factors for the development of SVT in SAP patients. A receiver operating characteristic (ROC) curve was generated to assess the predictive value of independent risk factors. Moreover, clinical complications and outcomes were compared between two groups. RESULTS: Among 177 SAP patients, 32 (18.1%) developed SVT. The most common cause of SAP was biliary (49.8%), followed by hypertriglyceridemia (21.5%). Multivariate logistic regression analyses showed that D-D (OR, 1.135; 95%CI, 1.043-1.236; p = 0.003) and fibrinogen degradation product (FDP) (OR, 1.037; 95%CI, 1.015-1.060; p = 0.001) were independent risk factors for SVT development in patients with SAP. The area under ROC curve for D-D was 0.891 (p = 0.003, sensitivity= 95.3%, specificity = 74.1%) at a cut-off value of 6.475, and the area under ROC curve for FDP was 0.858 (p = 0.001, sensitivity = 89.4%, specificity = 72.4%) at a cut-off value of 23.155. CONCLUSION: D-D and FDP are significant independent risk factors with high predictive value for SVT in patients with SAP.

Genetic association between coffee/caffeine consumption and the risk of obstructive sleep apnea in the European population: a two-sample Mendelian randomization study.

BACKGROUND: The association between coffee/caffeine consumption and obstructive sleep apnea (OSA) risk remains unclear. PURPOSE: To determine the relationship between coffee/caffeine consumption and the risk of OSA, using the Mendelian randomization (MR) method in the European population. METHODS: Two sets of coffee consumption-associated genetic variants were, respectively, extracted from the recent genome-wide meta-analysis (GWMA) and genome-wide association study (GWAS) of coffee consumption. Taking other caffeine sources into account, genetic variants associated with caffeine consumption from tea and plasma caffeine (reflecting total caffeine intake) were also obtained. The inverse variance weighted (IVW) technique was utilized as the primary analysis, supplemented by the MR-Egger, weighted-median, and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) techniques. Leave-one-out (LOO) analysis was performed to assess whether the overall casual estimates were driven by a single SNP. Additional sensitivity analyses were performed using similar methods, while the genetic variants associated with confounders, e.g., body mass index and hypertension, were excluded. RESULTS: The IVW method demonstrated that coffee consumption GWMA (OR: 1.065, 95% CI 0.927-1.224, p = 0.376), coffee consumption GWAS (OR: 1.665, 95% CI 0.932-2.977, p = 0.086), caffeine from tea (OR: 1.198, 95% CI 0.936-1.534, p = 0.151), and blood caffeine levels (OR: 1.054, 95% CI 0.902-1.231, p = 0.508) were unlikely to be associated with the risk of OSA. The other three methods presented similar results, where no significant associations were found. No single genetic variant was driving the overall estimates by the LOO analysis. These findings were also supported by the sensitivity analyses with no confounding genetic variants. CONCLUSION: Our study found no association between coffee/caffeine consumption and the risk of OSA.

Relationship between dietary carotenoid intake and sleep duration in American adults: a population-based study.

OBJECTIVE: To investigate the relationship between dietary carotenoid intake and sleep duration. METHODS: Adults enrolled in the National Health and Nutrition Examination Survey (NHANES) 2007-2018 without missing information on dietary carotenoid intake (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein + zeaxanthin), sleep duration, and covariates were included. Participants' carotenoid consumption was divided into three groups by quartiles and sleep duration was grouped as short (< 7 h/night), optimal (7-8 h/night), and long (> 8 h/night). Multinominal logistic regression was constructed to examine the association between dietary carotenoid intake and sleep duration. Restricted cubic spline (RCS) regression was further utilized to explore their dose-response relationship. The weighted quantile sum (WQS) model was adopted to calculate the mixed and individual effect of 5 carotenoid sub-types on sleep duration. RESULTS: Multinominal logistic regression presented that people with higher intakes of α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein + zeaxanthin were less likely to sleep too short or too long. Consistent with the findings from multinominal logistic regression, the RCS models suggested a reverse U-shaped relationship between sleep duration and carotenoid intakes. The mixed effects were also significant, where ß-cryptoxanthin and lutein + zeaxanthin were the top 2 contributors associated with the decreased risks of short sleep duration, while ß-carotene, α-carotene, and ß-cryptoxanthin were the main factors related to the lower risk of long sleep duration. CONCLUSION: Our study revealed that the American adults with optimal sleep duration were associated with more dietary carotenoid intake, in comparison to short or long sleepers.