Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid.

Bullous pemphigoid (BP) triggers profound functional changes in both immune and non-immune cells in the skin and circulation, though the underlying mechanisms remain unclear. In this study, we conduct single-cell transcriptome analysis of lesional and non-lesional skin, as well as blood samples from BP patients. In lesional skin, non-immune cells upregulate pathways related to metabolism, wound healing, immune activation, and cell migration.

Early esophageal cancer with mucosal bridging in the resting room: A case report.

Background: Patients diagnosed with esophageal mucosal bridges often experience symptoms such as chest pain and dysphagia, which pose considerable challenges for endoscopic surgical interventions.

Case Summary: We present a case involving early-stage esophageal cancer discovered in a resting room, notable for the rare manifestation of esophageal mucosal bridging. Following a comprehensive multidisciplinary discussion and the development of a treatment strategy, we proceeded with endoscopic submucosal dissection for the patient.

YELLOW, SERRATED LEAF is essential for cotyledon vein patterning in Arabidopsis.

Venation develops complex patterns within the leaves of angiosperms, and the mechanism of leaf vein patterning remains poorly understood. Here, we report a spontaneous mutant that exhibits yellow serrated leaves and defective cotyledon vein patterning. We mapped and cloned the relevant gene YELLOW, SERRATED LEAF (YSL), a previously unreported gene in plants.

Transcriptional and chromatin profiling of human blood innate lymphoid cell subsets sheds light on HIV-1 pathogenesis.

Innate lymphoid cells (ILCs) are a diverse population of cells that include NK cells and contribute to tissue homeostasis and repair, inflammation, and provide protection from infection. The interplay between human blood ILCs, as well as their responses to HIV-1 infection, remains poorly understood. This study used transcriptional and chromatin profiling to explore these questions.

Chloroplast inner envelope protein FtsH11 is involved in the adjustment of assembly of chloroplast ATP synthase under heat stress.

The maintenance of a proton gradient across the thylakoid membrane is an integral aspect of photosynthesis that is mainly established by the splitting of water molecules in photosystem II and plastoquinol oxidation at the cytochrome complex, and it is necessary for the generation of ATP in the last step of photophosphorylation. Although environmental stresses, such as high temperatures, are known to disrupt this fundamental process, only a few studies have explored the molecular mechanisms underlying proton gradient regulation during stress. The present study identified a heat-sensitive mutant that displays aberrant photosynthesis at high temperatures.

Optimization of Nuclear Localization Signal Composition Improves CRISPR-Cas12a Editing Rates in Human Primary Cells.

Type V CRISPR-Cas12a systems are an attractive Cas9-alternative nuclease platform for specific genome editing applications. However, previous studies demonstrate that there is a gap in overall activity between Cas12a and Cas9 in primary cells. Here we describe optimization to the NLS composition and architecture of Cas12a to facilitate highly efficient targeted mutagenesis in human transformed cell lines (HEK293T, Jurkat, and K562 cells) and primary cells (NK cells and CD34+ HSPCs), regardless of Cas12a ortholog.

HPR1 Is Required for High Light Intensity Induced Photorespiration in .

High light intensity as one of the stresses could lead to generation of large amounts of reactive oxygen species (ROS) in plants, resulting in severe plant growth retardation. The photorespiration metabolism plays an important role in producing and removing a variety of ROS, maintaining the dynamic balance of the redox reaction, and preventing photoinhibition. hydroxypyruvate reductase 1 (HPR1) is a primary metabolic enzyme in the photorespiration cycle.

Innate lymphoid cells and COVID-19 severity in SARS-CoV-2 infection.

Background: Risk of severe COVID-19 increases with age, is greater in males, and is associated with lymphopenia, but not with higher burden of SARS-CoV-2. It is unknown whether effects of age and sex on abundance of specific lymphoid subsets explain these correlations.

Methods: Multiple regression was used to determine the relationship between abundance of specific blood lymphoid cell types, age, sex, requirement for hospitalization, duration of hospitalization, and elevation of blood markers of systemic inflammation, in adults hospitalized for severe COVID-19 (n = 40), treated for COVID-19 as outpatients (n = 51), and in uninfected controls (n = 86), as well as in children with COVID-19 (n = 19), recovering from COVID-19 (n = 14), MIS-C (n = 11), recovering from MIS-C (n = 7), and pediatric controls (n = 17).

Innate lymphoid cells and disease tolerance in SARS-CoV-2 infection.

Risk of severe COVID-19 increases with age, is greater in males, and is associated with lymphopenia, but not with higher burden of SARS-CoV-2. It is unknown whether effects of age and sex on abundance of specific lymphoid subsets explain these correlations. This study found that the abundance of innate lymphoid cells (ILCs) decreases more than 7-fold over the human lifespan - T cell subsets decrease less than 2-fold - and is lower in males than in females.

Seedling Lethal 1 Interacting With Plastid-Encoded RNA Polymerase Complex Proteins Is Essential for Chloroplast Development.

Mitochondrial transcription termination factors (mTERFs) are highly conserved proteins in metazoans. Plants have many more mTERF proteins than animals. The functions and the underlying mechanisms of plants' mTERFs remain largely unknown.

The DHODH inhibitor PTC299 arrests SARS-CoV-2 replication and suppresses induction of inflammatory cytokines.

The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for therapeutics that inhibit the SARS-COV-2 virus and suppress the fulminant inflammation characteristic of advanced illness. Here, we describe the anti-COVID-19 potential of PTC299, an orally bioavailable compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine nucleotide biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS-COV-2 replication (EC range, 2.

Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant.

The SARS-CoV-2 spike (S) protein variant D614G supplanted the ancestral virus worldwide, reaching near fixation in a matter of months. Here we show that D614G was more infectious than the ancestral form on human lung cells, colon cells, and on cells rendered permissive by ectopic expression of human ACE2 or of ACE2 orthologs from various mammals, including Chinese rufous horseshoe bat and Malayan pangolin. D614G did not alter S protein synthesis, processing, or incorporation into SARS-CoV-2 particles, but D614G affinity for ACE2 was reduced due to a faster dissociation rate.

Rain Streaks Removal for Single Image via Kernel-Guided Convolutional Neural Network.

Recently emerged deep learning methods have achieved great success in single image rain streaks removal. However, existing methods ignore an essential factor in the rain streaks generation mechanism, i.e.

The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines.

The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for therapeutics that inhibit the SARS-CoV-2 virus and suppress the fulminant inflammation characteristic of advanced illness. Here, we describe the anti-COVID-19 potential of PTC299, an orally available compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS CoV-2 replication (EC range, 2.

Single-Cell RNA Profiling Reveals Adipocyte to Macrophage Signaling Sufficient to Enhance Thermogenesis.

Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWATs). Both cold exposure and iAdFASNKO upregulate the sympathetic nerve fiber (SNF) modulator Neuregulin 4 (Nrg4), activate SNFs, and require adipocyte cyclic AMP/protein kinase A (cAMP/PKA) signaling for beige adipocyte appearance, as it is blocked by adipocyte Gsα deficiency. Surprisingly, however, in contrast to cold-exposed mice, neither iWAT denervation nor Nrg4 loss attenuated adipocyte browning in iAdFASNKO mice.

Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant.

The SARS-CoV-2 spike (S) protein variant D614G supplanted the ancestral virus worldwide in a matter of months. Here we show that D614G was more infectious than the ancestral form on human lung cells, colon cells, and cells rendered permissive by ectopic expression of various mammalian ACE2 orthologs. Nonetheless, D614G affinity for ACE2 was reduced due to a faster dissociation rate.

Analysis of Risk Factors of Gastric Low-Grade Intraepithelial Neoplasia in Asymptomatic Subjects Undergoing Physical Examination.

Secondary prevention is an important strategy in gastric cancer. Low-grade intraepithelial neoplasia (LGIN) is the last stage of precancerous lesion, and its timely diagnosis can greatly improve the detection rate of early gastric cancer. We performed a prospective study to analyze the risk factors of gastric LGIN in asymptomatic subjects undergoing physical examination.

HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7-dependent memory NK cells.

Human immunodeficiency virus 1 (HIV-1) infection is associated with heightened inflammation and excess risk of cardiovascular disease, cancer and other complications. These pathologies persist despite antiretroviral therapy. In two independent cohorts, we found that innate lymphoid cells (ILCs) were depleted in the blood and gut of people with HIV-1, even with effective antiretroviral therapy.

Dichotomous regulation of group 3 innate lymphoid cells by nongastric species.

Intestinal innate lymphoid cells (ILCs) contribute to the protective immunity and homeostasis of the gut, and the microbiota are critically involved in shaping ILC function. However, the role of the gut microbiota in regulating ILC development and maintenance still remains elusive. Here, we identified opposing effects on ILCs by two species, and , isolated from immunocompromised mice.

miR-145 expression level in tissue predicts prognosis of patients with esophageal squamous cell carcinoma.

Background: MicroRNA-145 (miR-145) is commonly down-regulated and has been identified as a tumor-suppressive miRNA in multiple types of cancers, as well as in esophageal squamous cell carcinoma (ESCC). In the present study, the clinical significance and prognostic value were investigated in ESCC.

Methods: A total of 126 patients with ESCC who underwent surgery were included in the present study.

Association between alcohol intake and the risk of pancreatic cancer: a dose-response meta-analysis of cohort studies.

Background: Studies examining the association between alcohol intake and the risk of pancreatic cancer have given inconsistent results. The purpose of this study was to summarize and examine the evidence regarding the association between alcohol intake and pancreatic cancer risk based on results from prospective cohort studies.

Methods: We searched electronic databases consisting of PubMed, Ovid, Embase, and the Cochrane Library identifying studies published up to Aug 2015.

Bronchogenic cyst in the hepatogastric ligament masquerading as an esophageal mesenchymal tumor: a case report.

Lesions occur in hepatogastric gap is common, but most of these lesions are from stomach, lower esophagus and pancreas lesions extending or transferring to the gap. Lesions occurred in the hepatogastric ligament are rare, especially bronchogenic cysts in the hepatogastric ligament. So far, there were no relevant cases reported.

Casein kinase 1γ1 inhibits the RIG-I/TLR signaling pathway through phosphorylating p65 and promoting its degradation.

The casein kinase 1 (CK1) plays an important role in various biological processes by phosphorylating its target proteins. In this study, we demonstrate that CK1γ1 inhibits RNA virus-mediated activation of retinoic acid-inducible gene I (RIG-I) signaling by affecting the stability of NF-κB subunit p65. First, we found that ectopic expression of CK1γ1 inhibits RIG-I pathway-mediated activation of IFN-β, whereas knockdown of CK1γ1 potentiates the activation of IFN-β and NF-κB induced by Sendai virus (SeV).

Significance of glycosylphosphatidylinositol-anchored protein enrichment in lipid rafts for the control of autoimmunity.

Glycosylphosphatidylinositols (GPI) are complex glycolipids that are covalently linked to the C terminus of proteins as a post-translational modification and tether proteins to the plasma membrane. One of the most striking features of GPI-anchored proteins (APs) is their enrichment in lipid rafts. The biosynthesis of GPI and its attachment to proteins occur in the endoplasmic reticulum.