The highly conserved PIWI-interacting RNA CRAPIR antagonizes PA2G4-mediated NF110-NF45 disassembly to promote heart regeneration in mice.

Targeting the cardiomyocyte cell cycle is a promising strategy for heart repair following injury. Here, we identify a cardiac-regeneration-associated PIWI-interacting RNA (CRAPIR) as a regulator of cardiomyocyte proliferation. Genetic ablation or antagomir-mediated knockdown of CRAPIR in mice impairs cardiomyocyte proliferation and reduces heart regenerative potential.

Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity.

We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants.

The clinical effect of bone perforations in periodontal regeneration and alveolar socket preservation: a systematic review with meta-analysis.

Objectives: The present systematic review aimed to evaluate if cortical bone perforation is effective in enhancing periodontal surgery and guided bone regeneration (GBR) in humans.

Materials And Methods: Electronic search was performed in PubMed, Scopus and Cochrane CENTRAL up to October 31st, 2023. Grey literature was also searched.

"They knew the same struggles": perceptions of a group coping skills intervention in patients with chronic graft-versus-host disease.

Purpose: Chronic graft-versus-host-disease (cGVHD), an inflammatory condition affecting allogeneic hematopoietic cell transplantation (HCT) survivors, is associated with a range of debilitating physical and psychological sequela. Yet HCT recipients with cGVHD are virtually absent from survivorship intervention research. We conducted a randomized clinical trial to evaluate the feasibility and preliminary efficacy of a multidisciplinary group coping skills intervention (Horizons) tailored to meet these patients' unique needs.

Ticam2 ablation facilitates monocyte exhaustion recovery after sepsis.

Sepsis is a leading cause of death worldwide, with most patient mortality stemming from lingering immunosuppression in sepsis survivors. This is due in part to immune dysfunction resulting from monocyte exhaustion, a phenotype of reduced antigen presentation, altered CD14/CD16 inflammatory subtypes, and disrupted cytokine production. Whereas previous research demonstrated improved sepsis survival in Ticam2 mice, the contribution of TICAM2 to long-term exhaustion memory remained unknown.

Modeling the impact of extreme weather events and future climate on the radiologically contaminated sites of Enewetak Atoll.

Enewetak Atoll underwent 43 historical nuclear tests from 1948 to 1958, including the first hydrogen bomb test, resulting in a substantial nuclear material fallout contaminating the Atoll and the lagoon waters. The radionuclide fallout material deposited in lagoon sediments and soil on the islands will remain for decades to come. With intensifying climate and extreme weather events, the possibility of redistribution of deposited radionuclide material has become a great concern.

Environmental gradients shape genetic variation in the desert moss, Syntrichia caninervis Mitt. (Pottiaceae).

The moss Syntrichia caninervis Mitt. is distributed throughout drylands globally, and often anchors ecologically significant communities known as biological soil crusts (biocrusts). The species occupies a variety of dryland habitats with varying levels of drought and temperature stress, suggesting the potential for ecological specialization within S.

Advancing pancreatic cancer research and therapeutics: the transformative role of organoid technology.

Research on pancreatic cancer has transformed with the advent of organoid technology, providing a better platform that closely mimics cancer biology in vivo. This review highlights the critical advancements facilitated by pancreatic organoid models in understanding disease progression, evaluating therapeutic responses, and identifying biomarkers. These three-dimensional cultures enable the proper recapitulation of the cellular architecture and genetic makeup of the original tumors, providing insights into the complex molecular and cellular dynamics at various stages of pancreatic ductal adenocarcinoma (PDAC).

Asymmetric sensitivity of boreal forest resilience to forest gain and loss.

Forest gains and losses may have unequal effects on forest resilience, particularly given their distinct temporal dynamics. Here, we quantify the sensitivities of boreal forest resilience to forest cover gain and loss using a resilience indicator derived from the temporal autocorrelation (TAC) of the kernel normalized difference vegetation index from 2000 to 2020. Our findings unveil pronounced asymmetric sensitivities, with stronger sensitivity to forest loss (-4.

Loss of correlated proteasomal subunit expression selectively promotes the 20S state which underlies luminal breast tumorigenicity.

Why cancer cells disproportionately accumulate polyubiquitinated proteotoxic proteins despite high proteasomal activity is an outstanding question. While mis-regulated ubiquitination is a contributing factor, here we show that a structurally-perturbed and sub-optimally functioning proteasome is at the core of altered proteostasis in tumors. By integrating the gene coexpression signatures of proteasomal subunits in breast cancer (BrCa) patient tissues with the atomistic details of 26S holocomplex, we find that the transcriptional deregulation induced-stoichiometric imbalances perpetuate with disease severity.

Continental influx and pervasive matrilocality in Iron Age Britain.

Roman writers found the relative empowerment of Celtic women remarkable. In southern Britain, the Late Iron Age Durotriges tribe often buried women with substantial grave goods. Here we analyse 57 ancient genomes from Durotrigian burial sites and find an extended kin group centred around a single maternal lineage, with unrelated (presumably inward migrating) burials being predominantly male.

IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.

Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

Ancient DNA reveals reproductive barrier despite shared Avar-period culture.

After a long-distance migration, Avars with Eastern Asian ancestry arrived in Eastern Central Europe in 567 to 568 CE and encountered groups with very different European ancestry. We used ancient genome-wide data of 722 individuals and fine-grained interdisciplinary analysis of large seventh- to eighth-century CE neighbouring cemeteries south of Vienna (Austria) to address the centuries-long impact of this encounter. We found that even 200 years after immigration, the ancestry at one site (Leobersdorf) remained dominantly East Asian-like, whereas the other site (Mödling) shows local, European-like ancestry.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.

Specification of claustro-amygdalar and palaeocortical neurons and circuits.

The ventrolateral pallial (VLp) excitatory neurons in the claustro-amygdalar complex and piriform cortex (PIR; which forms part of the palaeocortex) form reciprocal connections with the prefrontal cortex (PFC), integrating cognitive and sensory information that results in adaptive behaviours. Early-life disruptions in these circuits are linked to neuropsychiatric disorders, highlighting the importance of understanding their development. Here we reveal that the transcription factors SOX4, SOX11 and TFAP2D have a pivotal role in the development, identity and PFC connectivity of these excitatory neurons.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Bilateral hip exoskeleton assistance enables faster walking in individuals with chronic stroke-related gait impairments.

Millions of individuals surviving a stroke have lifelong gait impairments that reduce their personal independence and quality of life. Reduced walking speed is one of the major problems limiting community mobility and reintegration. Previous studies have shown positive effect of robot-assisted gait training utilizing hip exoskeletons for individuals with gait impairments due to a stroke, leading to increased walking speed in post-treatment compared to pre-treatment assessments.

Precision fetal cardiology detects cyanotic congenital heart disease using maternal saliva metabolome and artificial intelligence.

Prenatal sonographic diagnosis of congenital heart disease (CHD) can lead to improved morbidity and mortality. However, the diagnostic accuracy of ultrasound, the sole prenatal screening tool, remains limited. Failed prenatal or early newborn detection of cyanotic CHD (CCHD) can have disastrous consequences.

Functional genomics implicates ebony in the black pupae phenotype of tephritid fruit flies.

The remarkable diversity of insect pigmentation offers a captivating avenue for studying evolution and genetics. In tephritids, understanding the molecular basis of mutant traits is also crucial for applied entomology, enabling the creation of genetic sexing strains through genome editing, thus facilitating sex-sorting before sterile insect releases. Here, we present evidence from classical and modern genetics showing that the black pupae (bp) phenotype in the GUA10 strain of Anastrepha ludens is caused by a large deletion at the ebony locus, removing the gene's entire coding region.

Plasma levels of anti phosphocholine IgM antibodies are negatively correlated with bone mineral density in humans.

Phosphatidylcholine is a ubiquitous phospholipid. It contains a phosphocholine (PC) headgroup and polyunsaturated fatty acids that, when oxidized, form reactive oxidized phospholipids (PC-OxPLs). PC-OxPLs are pathogenic in multiple diseases and neutralized by anti-PC IgM antibodies.

Treatment of patients with tumor/treatment-related hypothalamic obesity in the first two years following surgical treatment or radiotherapy.

Survivors of sellar/suprasellar tumors involving hypothalamic structures face a risk of impaired quality of life, including tumor- and/or treatment-related hypothalamic obesity (TTR-HO) defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor- and/or treatment related damage of the hypothalamus. We analyze German claims data to better understand treatment pathways for patients living TTR-HO during the two years following the index surgical treatment. A database algorithm identified patients with TTR-HO in a representative German payer claims database between 2010 and 2021 (n = 5.

Abnormality detection in nailfold capillary images using deep learning with EfficientNet and cascade transfer learning.

Nailfold Capillaroscopy (NFC) is a simple, non-invasive diagnostic tool used to detect microvascular changes in nailfold. Chronic pathological changes associated with a wide range of systemic diseases, such as diabetes, cardiovascular disorders, and rheumatological conditions like systemic sclerosis, can manifest as observable microvascular changes in the terminal capillaries of nailfolds. The current gold standard relies on experts performing manual evaluations, which is an exhaustive time-intensive, and subjective process.

Machine learning analysis of cervical balance in early-onset scoliosis post-growing rod surgery: a case-control study.

We aimed to analyze the cervical sagittal alignment change following the growing rod treatment in early-onset scoliosis (EOS) and identify the risk factors of sagittal cervical imbalance after growing-rod surgery of machine learning. EOS patients from our centre between 2007 and 2019 were retrospectively reviewed. Radiographic parameters include the cervical lordosis (CL), T1 slope, C2-C7 sagittal vertical axis (C2-7 SVA), primary curve Cobb angle, thoracic kyphosis (TK), C7-S1 sagittal vertical axis (C7-S1 SVA) and proximal junctional angle (PJA) were evaluated preoperatively, postoperatively and at the final follow-up.