Different molecular complexes that mediate transcriptional induction and repression by FoxP3.

FoxP3 conditions the transcriptional signature and functional facets of regulatory T cells (Treg cells). Its mechanism of action, whether as an activator or a repressor, has remained unclear. Here, chromatin analysis showed that FoxP3 bound active enhancer elements, not repressed chromatin, around loci over- or under-expressed in Treg cells. We evaluated the impact of a panel of FoxP3 mutants on its transcriptional activity and interactions with DNA, transcriptional cofactors and chromatin. Computational integration, confirmed by biochemical interaction and size analyses, showed that FoxP3 existed in distinct multimolecular complexes. It was active and primarily an activator when complexed with the transcriptional factors RELA, IKZF2 and KAT5. In contrast, FoxP3 was inactive when complexed with the histone methyltransferase EZH2 and transcription factors YY1 and IKZF3. The latter complex partitioned to a peripheral region of the nucleus, as shown by super-resolution microscopy. Thus, FoxP3 acts in multimodal fashion to directly activate or repress transcription, in a context- and partner-dependent manner, to govern Treg cell phenotypes.

Salmonella manipulates macrophage migration via SteC-mediated myosin light chain activation to penetrate the gut-vascular barrier.

The intestinal pathogen Salmonella enterica rapidly enters the bloodstream after the invasion of intestinal epithelial cells, but how Salmonella breaks through the gut-vascular barrier is largely unknown. Here, we report that Salmonella enters the bloodstream through intestinal CX3CR1+ macrophages during early infection. Mechanistically, Salmonella induces the migration/invasion properties of macrophages in a manner dependent on host cell actin and on the pathogen effector SteC. SteC recruits host myosin light chain protein Myl12a and phosphorylates its Ser19 and Thr20 residues. Myl12a phosphorylation results in actin rearrangement, and enhanced migration and invasion of macrophages. SteC is able to utilize a wide range of NTPs other than ATP to phosphorylate Myl12a. We further solved the crystal structure of SteC, which suggests an atypical dimerization-mediated catalytic mechanism. Finally, in vivo data show that SteC-mediated cytoskeleton manipulation is crucial for Salmonella breaching the gut vascular barrier and spreading to target organs.

Post-transcriptional polyadenylation site cleavage maintains 3'-end processing upon DNA damage.

The recognition of polyadenylation signals (PAS) in eukaryotic pre-mRNAs is usually coupled to transcription termination, occurring while pre-mRNA is chromatin-bound. However, for some pre-mRNAs, this 3'-end processing occurs post-transcriptionally, i.e., through a co-transcriptional cleavage (CoTC) event downstream of the PAS, leading to chromatin release and subsequent PAS cleavage in the nucleoplasm. While DNA-damaging agents trigger the shutdown of co-transcriptional chromatin-associated 3'-end processing, specific compensatory mechanisms exist to ensure efficient 3'-end processing for certain pre-mRNAs, including those that encode proteins involved in the DNA damage response, such as the tumor suppressor p53. We show that cleavage at the p53 polyadenylation site occurs in part post-transcriptionally following a co-transcriptional cleavage event. Cells with an engineered deletion of the p53 CoTC site exhibit impaired p53 3'-end processing, decreased mRNA and protein levels of p53 and its transcriptional target p21, and altered cell cycle progression upon UV-induced DNA damage. Using a transcriptome-wide analysis of PAS cleavage, we identify additional pre-mRNAs whose PAS cleavage is maintained in response to UV irradiation and occurring post-transcriptionally. These findings indicate that CoTC-type cleavage of pre-mRNAs, followed by PAS cleavage in the nucleoplasm, allows certain pre-mRNAs to escape 3'-end processing inhibition in response to UV-induced DNA damage.

Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia.

BACKGROUND: Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels. RESULTS: Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels. CONCLUSIONS: In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).

The role and mechanism of RIPK1 in vascular endothelial dysfunction in chronic kidney disease.

Endothelial dysfunction is common in patients with chronic kidney disease (CKD) and cardiovascular events, but the mechanism is unclear. In our study, we found elevated levels of RIPK1 in patients with CKD and cardiovascular events through bioinformation analysis. Elevated RIPK1 levels were found in serum samples of CKD patients and were associated with vascular endothelial dysfunction and renal function. We constructed the five of six nephrectomy of CKD mice model, finding that RIPK1 expressions were elevated in abdominal aorta endothelial cells. After RIPK1 inhibition and overexpression, it was found that RIPK1 could regulate the expression of endothelial nitric oxide synthase (eNOS) and cell adhesion molecule 1 (ICAM-1), and activation of inflammatory responses and endoplasmic reticulum (ER) stress. In addition, uremic toxin induced abnormal expression of RIPK1 in vitro. We observed RIPK1-mediating endothelial dysfunction and inflammation responses by ER stress pathways through gain and loss of function. In order to explore the specific mechanism, we conducted co-immunoprecipitation and expression regulation of RIPK1 and IKK, finding that RIPK1 formed complex with IKK and regulated IKK expression. In conclusion, we demonstrated that RIPK1 levels were closely associated with vascular endothelial dysfunction in patients with CKD. With uremic toxins, RIPK1 expression was elevated, which led to the activation of inflammation through the ER stress pathway, resulting in vascular endothelial injury. Besides, activation of RIPK1-IKK-NF-κB axis was a key driver of endothelial dysfunction in CKD. Our study provides a new perspective for the study of cardiovascular events in CKD.

Human-virus protein-protein interactions maps assist in revealing the pathogenesis of viral infection.

Many significant viral infections have been recorded in human history, which have caused enormous negative impacts worldwide. Human-virus protein-protein interactions (PPIs) mediate viral infection and immune processes in the host. The identification, quantification, localization, and construction of human-virus PPIs maps are critical prerequisites for understanding the biophysical basis of the viral invasion process and characterising the framework for all protein functions. With the technological revolution and the introduction of artificial intelligence, the human-virus PPIs maps have been expanded rapidly in the past decade and shed light on solving complicated biomedical problems. However, there is still a lack of prospective insight into the field. In this work, we comprehensively review and compare the effectiveness, potential, and limitations of diverse approaches for constructing large-scale PPIs maps in human-virus, including experimental methods based on biophysics and biochemistry, databases of human-virus PPIs, computational methods based on artificial intelligence, and tools for visualising PPIs maps. The work aims to provide a toolbox for researchers, hoping to better assist in deciphering the relationship between humans and viruses.

Click Conjugation of Zwitterionic Peptide with DNA Strand: An Efficient Antifouling Strategy for Versatile Photoelectrochemical Aptasensor.

Advanced antifouling biosensors have garnered considerable attention for their potential for precise and sensitive analysis in complex human bodily fluids. Herein, a pioneering approach was utilized to establish a robust and versatile photoelectrochemical aptasensor by conjugating a zwitterionic peptide with a DNA strand. Specifically, the branched zwitterionic peptide (BZP) was efficiently linked to complementary DNA (cDNA) through a click reaction, forming the BZP-cDNA conjugate. This intriguing conjugate exploited the BZP domain to create an antifouling biointerface, while the cDNA component facilitated subsequent hybridization with probe DNA (pDNA). To advance the development of the aptasensor, an upgraded PDA/HOF-101/ZnO ternary photoelectrode was designed as the signal converter for the modification of the BZP-cDNA conjugate, while a bipyridinium (MCEPy) molecule with strong electron-withdrawing properties was labeled at the front end of the pDNA to form the pDNA-MCEPy signal probe. Targeting the model of mucin-1, a remarkable enhancement in the photocurrent signal was achieved through exonuclease-I-aided target recycling. Such an engineered zwitterionic peptide-DNA conjugate surpasses the limitations imposed by conventional peptide-based sensing modes, exhibiting unique advantages such as versatility in design and capability for signal amplification.

Unveiling the seroprevalence of human papillomavirus in Guangdong, China: Implications for vaccination strategies.

Seroepidemiological characteristics of human papillomavirus (HPV) in community residents reflect natural infection and can guide the reform of vaccination programs. A population-based serological survey was conducted in Guangdong Province. Serum anti-HPV IgG antibody levels were determined by an ELISA. Neutralizing antibodies against HPV6, 11, 16, and 18 were detected via a pseudovirus-based neutralization assay (PBNA). A total of 5122 serum samples were collected from community residents, including 1989 males and 3133 females, in three cities of Guangdong Province. The rate of HPV IgG antibody positivity in females was 5.39% (95% CI: 4.6-6.2), which was greater than that in males (2.36%; 95% CI: 1.7-3.1). HPV IgG antibodies were more frequently detected in females aged 51-60 years (11.30%; 95% CI: 7.6-16.0), whereas in males, the detection increased with age and reached 4.94% (95% CI: 2.8-6.9) in the group aged ≥71 years. The seropositivity of neutralizing antibodies against HPV6 and 11 was greater than that against HPV16 and 18. The serum neutralizing antibody titers in individuals who received three doses of a vaccine were 7- to 12-fold greater than those in individuals who did not receive the vaccine. The neutralizing antibody titers slightly decreased within 40 months and ranged from 0.038 to 0.057 log ED50 per month. A moderate consistency between the HPV ELISA and PBNA results was observed (Kappa score = 0.49, r = 0.249, 0.635, 0.382, and 0.466 for HPV6, 11, 16, and 18, respectively). The HPV seropositivity rate among healthy residents of Guangdong Province was found to be low among children and adolescents and to increase with age. The serum neutralizing antibody titers were significantly greater in the vaccine group than that in the control group, and this difference persisted over time, which indicated promising protection against HPV infection.

Microbial reconstitution reverses prenatal stress-induced cognitive impairment and synaptic deficits in rat offspring.

Stress during pregnancy is often linked with increased incidents of neurodevelopmental disorders, including cognitive impairment. Here, we report that stress during pregnancy leads to alterations in the intestinal flora, which negatively affects the cognitive function of offspring. Cognitive impairment in stressed offspring can be reproduced by transplantation of cecal contents of stressed pregnant rats (ST) to normal pregnant rats. In addition, gut microbial dysbiosis results in an increase of ß-guanidinopropionic acid in the blood, which leads to an activation of the adenosine monophosphate-activated protein kinase (AMPK) and signal transducer and activator of transcription 3 (STAT3) in the fetal brain. Moreover, ß-guanidinopropionic acid supplementation in pregnant rats can reproduce pregnancy stress-induced enhanced glial differentiation of the fetal brain, resulting in impaired neural development. Using probiotics to reconstruct maternal microbiota can correct the cognitive impairment in the offspring of pregnant stressed rats. These findings suggest that microbial reconstitution reverses gestational stress-induced cognitive impairment and synaptic deficits in male rat offspring.

New avenues of combating antibiotic resistance by targeting cryptic pockets.

Antibiotic resistance is a global health concern that is rapidly spreading among human and animal pathogens. Developing novel antibiotics is one of the most significant approaches to surmount antibiotic resistance. Given the difficult in identifying novel targets, cryptic binding sites provide new pockets for compounds design to combat antibiotic resistance. However, there exists a lack of comprehensive analysis and discussion on the successful utilization of cryptic pockets in overcoming antibiotic resistance. Here, we systematically analyze the crucial role of cryptic pockets in neutralizing antibiotic resistance. First, antibiotic resistance development and associated resistance mechanisms are summarized. Then, the advantages and mechanisms of cryptic pockets for overcoming antibiotic resistance were discussed. Specific cryptic pockets in resistant proteins and successful case studies of designed inhibitors are exemplified. This review provides insight into the discovery of cryptic pockets for drug design as an approach to overcome antibiotic resistance.

An inflammation-based model for identifying severe acute pancreatitis: a single-center retrospective study.

BACKGROUND AND AIMS: Severe acute pancreatitis (SAP) is potentially lethal. Considering the role of inflammation in the progression of acute pancreatitis (AP), this study aims to develop a model based on inflammatory indexes for identifying the presence of SAP. METHODS: Overall, 253 patients with AP who were consecutively admitted between July 2018 and November 2020 were screened, of whom 60 had SAP. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-platelet ratio (NPR), systemic inflammation response index (SIRI), platelet-to-albumin ratio (PAR), C-reactive protein-to-albumin ratio (CAR), C-reactive protein-to-lymphocyte ratio (CLR), and triglyceride glucose (TyG) index were calculated. Multivariate logistic regression analyses were performed to identify independent risk factors of SAP. Then, inflammation-based models were established. Receiver operating characteristics (ROC) curve analyses were performed. Area under ROC curve (AUROC) was calculated. RESULTS: Diabetes mellitus, fatty liver, high white blood cell count (WBC), C-reactive protein (CRP), red blood cell distribution width (RDW), procalcitonin (PCT), SII, NLR, NPR, CAR, CLR, and TyG index, and a low LMR were significantly associated with SAP. Considering the collinearity among these variables, 10 multivariate logistic regression analyses were separately performed. Finally, four independent inflammation-based models were established. Of them, the best one, which was calculated as follows: 1.204*fatty liver (yes = 1; no = 0) + 0.419*PCT + 0.005*CLR - 2.629, had an AUROC of 0.795 with a specificity of 73.4% and a sensitivity of 71.7%. CONCLUSION: The inflammation-based model consisting of fatty liver, PCT, and CLR has a good diagnostic performance for SAP.

Different computational relations in language are captured by distinct brain systems.

A critical way for humans to acquire information is through language, yet whether and how language experience drives specific neural semantic representations is still poorly understood. We considered statistical properties captured by 3 different computational principles of language (simple co-occurrence, network-(graph)-topological relations, and neural-network-vector-embedding relations) and tested the extent to which they can explain the neural patterns of semantic representations, measured by 2 functional magnetic resonance imaging experiments that shared common semantic processes. Distinct graph-topological word relations, and not simple co-occurrence or neural-network-vector-embedding relations, had unique explanatory power for the neural patterns in the anterior temporal lobe (capturing graph-common-neighbors), inferior frontal gyrus, and posterior middle/inferior temporal gyrus (capturing graph-shortest-path). These results were relatively specific to language: they were not explained by sensory-motor similarities and the same computational relations of visual objects (based on visual image database) showed effects in the visual cortex in the picture naming experiment. That is, different topological properties within language and the same topological computations (common-neighbors) for language and visual inputs are captured by different brain regions. These findings reveal the specific neural semantic representations along graph-topological properties of language, highlighting the information type-specific and statistical property-specific manner of semantic representations in the human brain.

Dietary polyunsaturated fatty acids intake is negatively associated with hyperuricemia: The National Health and Nutrition Examination Survey 2003-2015.

BACKGROUND AND AIMS: The objective of this research was to explore the associations between dietary PUFAs intake and hyperuricemia risk. METHODS AND RESULTS: Based on the National Health and Nutrition Examination Survey (NHANES) 2003-2015, all eligible individuals were divided into hyperuricemia and non-hyperuricemia groups based on diagnostic criteria for hyperuricemia (serum uric acid >420 µmol/L for men and >360 µmol/L for women). Multivariate-adjusted logistic regression was employed to explore the relationship between dietary PUFAs intake and hyperuricemia risk. Total PUFAs and their subtypes were modeled to isocalorically replace saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Higher intake of n-3 PUFAs, n-6 PUFAs, linoleic acid (LA), alpha-linoleic acid (ALA), and non-marine PUFAs intake correlated with decreased hyperuricemia risk, with adjusted odds ratio (OR) and 95% confidence interval (95%CIs) were 0.77 (0.63, 0.93), 0.75 (0.61, 0.92), 0.75 (0.61, 0.91), 0.69 (0.55, 0.87), and 0.73 (0.59, 0.91), respectively. Replacing 5% of total energy intake from SFAs with isocaloric PUFAs was associated with decreased odds of hyperuricemia in men (0.69 (0.57, 0.84)) and in individuals (0.81 (0.71, 0.92)). Similar trends were observed in the substitution of SFAs with non-marine PUFAs in men (0.87 (0.80, 0.94)) and in all individuals (0.92 (0.88, 0.98)). Sensitivity analyses exhibited consistent results with primary analyses. CONCLUSION: Higher dietary intake of n-3 PUFAs, n-6 PUFAs, LA, ALA, and non-marine PUFAs was associated with decreased hyperuricemia risk. These results support the recommendation to substitute SFAs with PUFAs in diet.

Solvent effect in H-BEA catalyzed cyclohexanol dehydration reaction.

The solvent effect on H-BEA catalyzed cyclohexanol dehydration was investigated in water, dioxane, and cyclohexanol. The dynamic evolution of the Brønsted acid site of zeolite and its interaction with reactant molecules in different solvents were explored with ab initio molecular dynamics simulations, providing reliable configuration sampling to obtain configurations at equilibrium. Solvent profoundly changes the adsorption as well as the dehydration reaction of cyclohexanol in H-BEA, where the reaction is determined to follow the E2 mechanism in water and dioxane but the E1 mechanism in cyclohexanol untill saturation uptake. Near saturation uptake, all three solvents significantly reduce the cyclohexanol dehydration rates in H-BEA. Cyclohexanol loading also dramatically affects the kinetics of the dehydration reaction, displaying an overall decreasing trend with a local minimum present at intermediate loading of 6 molecules per unit cell, which is a result of the entropic effect associated with greater freedom of motion of the transition state. Rigorous quantification of enthalpy and entropy contributions to cyclohexanol adsorption and activation shed light on the solvent effect of zeolite-catalyzed alcohol dehydration.

Nanomaterial-integrated injectable hydrogels for craniofacial bone reconstruction.

The complex anatomy and biology of craniofacial bones pose difficulties in their effective and precise reconstruction. Injectable hydrogels (IHs) with water-swollen networks are emerging as a shape-adaptive alternative for noninvasively rebuilding craniofacial bones. The advent of versatile nanomaterials (NMs) customizes IHs with strengthened mechanical properties and therapeutically favorable performance, presenting excellent contenders over traditional substitutes. Structurally, NM-reinforced IHs are energy dissipative and covalently crosslinked, providing the mechanics necessary to support craniofacial structures and physiological functions. Biofunctionally, incorporating unique NMs into IH expands a plethora of biological activities, including immunomodulatory, osteogenic, angiogenic, and antibacterial effects, further favoring controllable dynamic tissue regeneration. Mechanistically, NM-engineered IHs optimize the physical traits to direct cell responses, regulate intracellular signaling pathways, and control the release of biomolecules, collectively bestowing structure-induced features and multifunctionality. By encompassing state-of-the-art advances in NM-integrated IHs, this review offers a foundation for future clinical translation of craniofacial bone reconstruction.

A study on the morphology of iliac crest based on the objectives of jaw bone defect reconstruction.

OBJECTIVES: to understand the morphological characteristics of iliac crest and provide advice and assistance for jaw bone reconstruction with iliac bone flap by evaluating the thickness and curvature of iliac crest. MATERIALS AND METHODS: 100 patients who had taken Spiral CT of the Abdominal region before surgeries between 2020 and 2022 were included in this study. 3D reconstruction images of the iliac bones were created. 5 vertical planes perpendicular to the iliac crest were made every 2 cm along the centerline of the iliac crest (VP2 ~ VP10). On these vertical planes, 4 perpendicular lines were made every 1 cm along the long axis of the iliac crest (D1 ~ D4). The thicknesses at these sites, horizontal angle (HA) of iliac crest and the distance between inflection point and the central point of anterior superior iliac spine (DIA) were measured. RESULTS: The thickness of iliac bone decreased significantly from D1 ~ D4 on VP6 ~ VP10 and from VP2 ~ VP10 on D3 and D4 level (P<0.05). HA of iliac crests was 149.13 ± 6.92°, and DIA was 7.36 ± 1.01 cm. Iliac bone thickness, HA and DIA had very weak or weak correlation with patient's age, height and weight. CONCLUSIONS: The average thicknesses of iliac crest were decreased approximately from front to back, from top to bottom. The thickness and curvature of the iliac crest were difficult to predict by age, height and weight. CLINICAL RELEVANCE: Virtual surgical planning is recommended before jaw bone reconstruction surgery with iliac bone flap, and iliac crest process towards alveolar process might be a better choice.

Analysis of changes in bone mineral density and cortical bone thickness after reconstruction of the mandible with fibula, is condyle preservation a critical influence factor?

OBJECTIVE: This study aimed to investigate the features of bone mineral density (BMD) and cortical bone thickness in grafted fibula. MATERIALS AND METHODS: Eighty-six patients who underwent mandibular reconstruction using vascularized fibula flaps were enrolled, all of whom were followed up at 3, 6, and 12 months after surgery. The patients were grouped according to whether the condyle was preserved. BMD and cortical bone thickness were also measured. RESULTS: Condyle-preserved group consisted of 65 patients and condyle-unpreserved group consisted of 21 patients. There was a significant correlation between thickness and BMD, which was significantly correlated with follow-up time. One year after surgery, the BMD of the condyle-preserved group decreased from 1029.61 ± 156.01 mg/cm3 to 978.6 ± 141.90 mg/cm3, and thickness decreased from 3.29 ± 0.65 mm to 2.72 ± 0.72 mm. BMD of the condyle-unpreserved group decreased from 1062.21 ± 126.01 mg/cm3 to 851.26 ± 144.38 mg/cm3, and thickness decreased from 3.46 ± 0.89 mm to 2.56 ± 0.73 mm. In the condyle-preserved and unpreserved groups, the absorption rates of BMD were 3.29 ± 11.97% and 17.09 ± 12.42% at 12 months, respectively, and the rate of thickness was 20.7 ± 11.45% and 26.39 ± 12.23% at 12 months, respectively. CONCLUSION: BMD and thickness showed a decreasing trend over time. Preserving the condyle can slow bone resorption of the fibula. Regarding implant restoration, we recommend doctors to perform the treatment within 6-12 months after surgery in order to effectively manage bone resorption. CLINICAL RELEVANCE: Our study found that condylar preservation can decrease the absorption rate of BMD and cortical bone thickness, helping doctors make better clinical decisions. TRIAL REGISTRATION NUMBER: ChiCTR2300069661 (March 22, 2023).

Artificial intelligence-assisted oculo-gait measurements for cognitive impairment in cerebral small vessel disease.

INTRODUCTION: Oculomotor and gait dysfunctions are closely associated with cognition. However, oculo-gait patterns and their correlation with cognition in cerebral small vessel disease (CSVD) remain unclear. METHODS: Patients with CSVD from a hospital-based cohort (n = 194) and individuals with presumed early CSVD from a community-based cohort (n = 319) were included. Oculo-gait patterns were measured using the artificial intelligence (AI) -assisted 'EyeKnow' eye-tracking and 'ReadyGo' motor evaluation systems. Multivariable linear and logistic regression models were employed to investigate the association between the oculo-gait parameters and cognition. RESULTS: Anti-saccade accuracy, stride velocity, and swing velocity were significantly associated with cognition in both patients and community dwellers with CSVD, and could identify cognitive impairment in CSVD with moderate accuracy (area under the curve [AUC]: hospital cohort, 0.787; community cohort, 0.810) after adjusting for age and education. DISCUSSION: The evaluation of oculo-gait features (anti-saccade accuracy, stride velocity, and swing velocity) may help screen cognitive impairment in CSVD. HIGHLIGHTS: Oculo-gait features (lower anti-saccade accuracy, stride velocity, and swing velocity) were associated with cognitive impairment in cerebral small vessel disease (CSVD). Logistic model integrating the oculo-gait features, age, and education level moderately distinguished cognitive status in CSVD. Artificial intelligence-assisted oculomotor and gait measurements provide quick and accurate evaluation in hospital and community settings.

What have single-molecule studies taught us about gene expression?

The production of a single mRNA is the result of many sequential steps, from docking of transcription factors to polymerase initiation, elongation, splicing, and, finally, termination. Much of our knowledge about the fundamentals of RNA synthesis and processing come from ensemble in vitro biochemical measurements. Single-molecule approaches are very much in this same reductionist tradition but offer exquisite sensitivity in space and time along with the ability to observe heterogeneous behavior and actually manipulate macromolecules. These techniques can also be applied in vivo, allowing one to address questions in living cells that were previously restricted to reconstituted systems. In this review, we examine the unique insights that single-molecule techniques have yielded on the mechanisms of gene expression.

The Complete Mitochondrial Genome of the Siberian Scoter Melanitta stejnegeri and Its Phylogenetic Relationship in Anseriformes.

The Siberian Scoter (Melanitta stejnegeri) is a medium sea duck distinct from M. deglandi due to the absence of hybridization and differences in morphological characteristics. However, knowledge of its phylogenetic relationships within Anseriformes is limited due to a lack of molecular data. In this study, the complete mitogenome of M. stejnegeri was firstly sequenced, then annotated and used to reconstruct the phylogenetic relationships of 76 Anseriformes species. The complete mitogenome of M. stejnegeri is 16,631 bp and encodes 37 typical genes: 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and 1 non-coding control region. Its mitogenome organization is similar to that of other Anseriformes species. The phylogenetic relationships within the genus Melanitta are initially clarified, with M. americana at the base. M. stejnegeri and M. deglandi are sister groups, clustering with M. fusca and M. perspicillata in order. Phylogenetic analysis suggests that Mareca falcata and M. strepera are sister groups, differing from previous studies. Results firstly indicate that Clangula hyemalis and Somateria mollissima are sister groups, suggesting a potentially skewed phylogenetic relationship may have been overlooked in earlier analyses relying solely on mitochondrial genomes. Our results provide new mitogenome data to support further phylogenetic and taxonomic studies of Anseriformes.