Neurofilament heavy chain in secondary progressive multiple sclerosis.

Background: Biomarkers are needed to track progression in MS trials. Neurofilament heavy chain (NfH) has been underutilized due to assay limitations.

Objective: To investigate the added value of cerebrospinal fluid (CSF) NfH in secondary progressive multiple sclerosis (SPMS) using contemporary immunoassays.

Dynamic in vivo monitoring of granum structural changes of Ctenanthe setosa (Roscoe) Eichler during drought stress and subsequent recovery.

Investigating the effects of drought stress and subsequent recovery on the structure and function of chloroplasts is essential to understanding how plants adapt to environmental stressors. We investigated Ctenanthe setosa (Roscoe) Eichler, an ornamental plant that can tolerate prolonged drought periods (40 and 49 days of water withdrawal). Conventional biochemical, biophysical, physiological and (ultra)structural methods combined for the first time in a higher plant with in vivo small-angle neutron scattering (SANS) were used to characterize the alterations induced by drought stress and subsequent recovery.

Seagrass wasting disease prevalence and lesion area increase with invertebrate grazing across the northeastern Pacific.

Disease is a key driver of community and ecosystem structure, especially when it strikes foundation species. In the widespread marine foundation species eelgrass (Zostera marina), outbreaks of wasting disease have caused large-scale meadow collapse in the past, and the causative pathogen, Labyrinthula zosterae, is commonly found in meadows globally. Research to date has mainly focused on abiotic environmental drivers of seagrass wasting disease, but there is strong evidence from other systems that biotic interactions such as herbivory can facilitate plant diseases.

Application of Multiple Base-Editing Mediated by Polycistronic tRNA-gRNA-Processing System in Pig Cells.

Gene edited pigs have extensive and important application value in the fields of agriculture and biomedicine. With the increasing demand in medical research and agricultural markets, more and more application scenarios require gene edited pigs to possess two or even more advantageous phenotypes simultaneously. The current production of multi gene edited pigs is inefficient, time-consuming, and costly, and there is an urgent need to develop efficient and accurate multi gene editing application technologies.

Free-Hand Endoscopic Full-Thickness Resection for Duodenal Subepithelial Lesions.

Background And Aim: This work aims to evaluate the efficacy and safety of free-hand endoscopic full-thickness resection (EFTR) for duodenal subepithelial lesions (SELs).

Methods: We performed a retrospective review of 105 patients with duodenal SELs who underwent free-hand EFTR. Free-hand EFTR means no other devices (over-the-scope clip or full-thickness resection device) are required.

Associations of maternal night shift work during pregnancy with DNA methylation in offspring: a meta-analysis in the PACE consortium.

Background: Night shift work during pregnancy has been associated with differential DNA methylation in placental tissue, but no studies have explored this association in cord blood. We aimed to examine associations of maternal night shift work with cord blood DNA methylation.

Methods: A total of 4487 mother-newborn pairs from 7 studies were included.

Tensile force promotes osteogenic differentiation via ephrinB2-EphB4 signaling pathway in orthodontic tooth movement.

Objective: To investigating whether osteogenic differentiation of osteoblasts promoted by tension force (TF) is mediated by ephrinB2-EphB4 signaling.

Methods: TF was applied to MC3T3-E1 cells, then CCK-8 and live/dead staining were used to detect cell proliferation. Levels of osteogenic differentiation-related factors were detected by ALP staining, ARS staining, qPCR and western blot.

Bisecting GlcNAc modification of vesicular GAS6 regulates CAFs activation and breast cancer metastasis.

Background: Cancer-associated fibroblasts (CAFs) are a pivotal component of the tumor microenvironment (TME), playing key roles in tumor initiation, metastasis, and chemoresistance. While glycosylation is known to regulate various cellular processes, its impact on CAFs activation remains insufficiently explored.

Methods: We assessed the correlation between bisecting GlcNAc levels and CAFs markers (α-SMA, PDGFRA, PDGFRB) in breast cancer tissues.

Safety and efficacy of intravenous thrombolysis: a systematic review and meta-analysis of 93,057 minor stroke patients.

Background: The definition of minor ischemic stroke (MIS) is a topic of debate, however, the most accepted definition is a stroke with National Institutes of Health Stroke Scale (NIHSS) ≤ 5. Intravenous thrombolysis (IVT) is a crucial treatment option for acute ischemic stroke (AIS) including: alteplase, recombinant human tissue-type plasminogen activator (r-tPA), and the recently approved tenecteplase. However, there is a debate regarding its safety and efficacy.

Clinical and Mycobacterium tuberculosis strain characteristics of tuberculosis patients with diabetes mellitus in Changping District, Beijing, China.

Background: Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB), However, limited research exists on their clinical and strain characteristics. This study aims to investigate the correlation between these factors in TB-DM patients in Changping District.  METHODS: Whole genome sequencing (WGS) and drug susceptibility tests (DST) were performed on culture-positive strains.

The accumulation of harmful genes within the ROH hotspot regions of the Tibetan sheep genome does not lead to genetic load.

Background: Prolonged natural selection and artificial breeding have contributed to increased uniformity within the Tibetan sheep population, resulting in a reduction in genetic diversity and the establishment of selective signatures in the genome. This process has led to a loss of heterozygosity in specific genomic regions and the formation of Runs of Homozygosity (ROH). Current research on ROH predominantly focuses on inbreeding and the signals of selection; however, there is a paucity of investigation into the genetic load and selective pressures associated with ROH, both within these regions and beyond.

Isolation, characterization and therapeutic efficacy of lytic bacteriophage ZK22 against Salmonella Typhimurium in mice.

Background: Salmonella enterica serovar Typhimurium is one of the most common serovars of Salmonella associated with clinical cases. It not only leads to diarrhea and mortality raised in livestock and poultry farming, but also poses a risk to food safety.

Results: In this study, a lytic bacteriophage named ZK22 was isolated and identified from sewage.

Chronic restraint stress affects the diurnal rhythms of gut microbial composition and metabolism in a mouse model of depression.

Background: Depression is a common mental disorder accompanied by gut microbiota dysbiosis, which disturbs the metabolism of the host. While diurnal oscillation of the intestinal microbiota is involved in regulating host metabolism, the characteristics of the intestinal microbial circadian rhythm in depression remain unknown. Our aim was to investigate the microbial circadian oscillation signature and related metabolic pathways in a mouse model with depression-like behaviours.

Genomic selection strategies to overcome genotype by environment interactions in biosecurity-based aquaculture breeding programs.

Background: Family-based selective breeding programs typically employ both between-family and within-family selection in aquaculture. However, these programs may exhibit a reduced genetic gain in the presence of a genotype by environment interactions (G × E) when employing biosecurity-based breeding schemes (BS), compared to non-biosecurity-based breeding schemes (NBS). Fortunately, genomic selection shows promise in improving genetic gain by taking within-family variance into account.

IFN-γ reprograms cardiac microvascular endothelial cells to mediate doxorubicin transport and influences the sensitivity of mice to doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is a first-line chemotherapy agent known for its cardiac toxicity. DOX-induced cardiotoxicity (DIC) severely limits the use for treating malignant tumors and is associated with a poor prognosis. The sensitivity to DIC varies among patients, but the precise mechanisms remain elusive.

Multi-locus inherited neoplasia alleles syndromes in cancer: implications for clinical practice.

The popularity of multi-gene testing has identified more families with two or more pathogenic variants (PV) in cancer predisposition genes, also known as 'MINAS' (multilocus inherited neoplasia alleles syndromes). They are at risk of suboptimal treatment and management as little on this topic is known. We conducted a systematic review of published MINAS cases within cancer predisposition genes to understand their association with more severe presentations.

Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39.

Microglia and the border-associated macrophages contribute to the modulation of cerebral blood flow, but the mechanisms have remained uncertain. Here, we show that microglia regulate the cerebral blood flow baseline and the responses to whisker stimulation or intra-cisternal magna injection of adenosine triphosphate, but not intra-cisternal magna injection of adenosine in mice model. Notably, microglia repopulation corrects these cerebral blood flow anomalies.

Mgl2 cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice.

Fungal spores are abundant in the environment and a major cause of asthma. Originally characterised as a type 2 inflammatory disease, allergic airway inflammation that underpins asthma can also involve type 17 inflammation, which can exacerbate disease causing failure of treatments tailored to inhibit type 2 factors. However, the mechanisms that determine the host response to fungi, which can trigger both type 2 and type 17 inflammation in allergic airway disease, remain unclear.

Low emotional contagious behavior induces PTSD susceptibility in observers and is related to the regulation of oxytocin receptor in mice.

Background: Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder that occurs after an individual has witnessed or experienced a major traumatic event. Emotional contagion seems to play an important role in witnessing trauma, highlighting the importance of understanding the neurobiological consequences of psychological or emotional stress and its impact on the individual's mental health. Therefore, understanding the relationship between emotional contagion and PTSD susceptibility and the abnormal neurobiological and behavioral changes behind it could help find effective molecular treatment targets.

The Impact of Family History on Clinical Presentation and Biologic Treatment Response in Patients with Psoriasis: A Multicenter Prospective Cohort Study.

Background: Family history (FH) of psoriasis has been implicated as a risk factor for developing psoriasis. However, whether FH also carries information on clinical presentation and treatment response to biological agents in patients with psoriasis remains unclear.

Objective: This prospective, multicenter observational study aimed to analyze the clinical presentation and efficacy differences between patients with psoriasis with and without a FH.

Policy options for sustainable access to off-patent antibiotics in Europe.

Securing sustainable access to existing antibiotics optimises agent choice for individual treatments and is crucial to curb antibiotic resistance. Access to antibiotics is often restricted in many countries, due to general market unavailability or episodic shortages. This article outlines key policy options to maintain availability of existing antibiotics and enhance antibiotic supply chain resilience focusing on the perspectives of European Union (EU) and European Economic Area (EEA) institutions and member states.

Extended quantum anomalous Hall states in graphene/hBN moiré superlattices.

Electrons in topological flat bands can form new topological states driven by correlation effects. The pentalayer rhombohedral graphene/hexagonal boron nitride (hBN) moiré superlattice was shown to host fractional quantum anomalous Hall effect (FQAHE) at approximately 400 mK (ref. ), triggering discussions around the underlying mechanism and role of moiré effects.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Immune evasion through mitochondrial transfer in the tumour microenvironment.

Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses. However, detailed mechanisms of such processes remain unclear.

An Exploratory Investigation of Heritage and Educational Language Exposures as Factors in Medical Student Spanish Language Proficiency.

Background: Prior to enrolling in medical Spanish courses, students typically acquire their Spanish skills either through formal second language education only (L2 learners) or by being exposed to Spanish during childhood at home (heritage learners).

Objective: To categorize the language exposures of medical students who participated in a medical Spanish course and explore the associations of exposures with their medical language proficiency score on the Physician Oral Language Observation Matrix (POLOM).

Setting And Participants: Forty-one fourth-year medical students (2021-2022) self-reported demographics and prior language exposures and participated in videorecorded POLOM-rated Spanish standardized patient encounters.