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Many corals form a mutually beneficial relationship with the dinoflagellate algae calledSymbiodiniaceae. Cells in the coral gastrodermis recognize, phagocytose, and house the algae in an organelle called symbiosome, which supports algae photosynthesis and nutrient exchange with corals1–3. Rising ocean temperature disrupts this endosymbiotic relationship, leading to alga loss, coral bleaching and death, and the degradation of marine ecosystems4–6. Mitigation of coral death requires a mechanistic understanding of coral-algal endosymbiosis. We have developed genomic resources to enable the use of a soft coralXenia speciesas a model to study coral-algal endosymbiosis7. Here we report an effective RNA interference (RNAi) method and its application in the functional studies of genes involved in early steps of endosymbiosis. We show that an endosymbiotic cell marker called LePin (for itsLectin and kazalProteaseinhibitor domains) is a secreted lectin that binds to algae to initiate the formation of alga-containing endosymbiotic cells. The evolutionary conservation of LePin among marine endosymbiotic anthozoans suggests a general role in coral-algal recognition. Coupling bioinformatics analyses with RNAi and single cell (sc)-RNA-seq, we uncover three gene expression programs (GEP) influenced by LePin during the early and middle stages of endosymbiotic lineage development. Further studies of genes in these GEPs lead to the identification of two scavenger receptors that support the formation of alga-containing endosymbiotic cells, most likely by initiating phagocytosis and modulating coral immune response. We also identify two actin regulators for endosymbiosis, which shed light on the phagocytic machinery and a possible mechanism for symbiosome formation. Our findings should usher in an era of mechanistic studies of coral-algal endosymbiosis.

The computational inference of genome organization based on Hi-C sequencing has greatly aided the understanding of chromatin and nuclear organization in three dimensions (3D). However, existing computational methods used to infer sub-compartments from Hi-C data fail to address the cell population heterogeneity. Here we describe a model-based method, called CscoreTool-M, which uses probabilistic modeling to build multiple 3D genome sub-compartments from Hi-C data. The compartment scores inferred using CscoreTool-M directly represents the probability of a genomic region locating in a specific sub-compartment. Compared to published methods, CscoreTool-M is more accurate in inferring local sub-compartment containing heterochromatin marked by Histone lysine trimethylation (H3K27me3) surrounded by the actively transcribed euchromatic regions. The compartment scores calculated by CscoreTool-M also help to quantify the levels of heterogeneity in sub-compartment localization within cell populations for different genomic regions. By comparing proliferating cells and terminally differentiated non-proliferating cells, we show that the proliferating cells have higher genome organization heterogeneity, which is likely caused by cells at different cell-cycle stages. By analyzing 10 sub-compartments, we found a sub-compartment containing chromatin potentially related to the early-G1 chromatin regions proximal to the nuclear lamina in HCT116 cells, suggesting the method can deconvolve cell cycle stage-specific genome organization among asynchronously dividing cells. Finally, we show that CscoreTool-M can further identify sub-compartments that contain genes enriched in housekeeping or cell-type-specific functions.

ObjectiveEarly-onset colorectal cancer (CRC) is increasing in many developed countries. Type 2 diabetes mellitus has increased substantially in younger adults; however, its role in early-onset CRC remains unidentified.DesignWe conducted a claims-based nested case-control study using IBM® MarketScan® Commercial Database (2006-2015). Incident early-onset CRC diagnosed at ages 18-49 were identified by ICD-9-CM diagnosis code, and the first coded diagnostic pathology date was assigned as the index date. Controls were frequency matched with cases. Type 2 diabetes, stratified by severity, was identified through ICD-9-CM using the Klabunde algorithm. Multivariate logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (Cls).ResultsA total of 6001 early-onset CRC and 52104 controls were included. Type 2 diabetes was associated with an increased risk of early-onset CRC (5.0% in cases vs. 3.7% in controls; OR 1.24; 95% CI 1.09 to 1.41). The positive association was more pronounced for uncontrolled (OR 1.37; 95% CI 1.12 to 1.67) or complicated (OR 1.59; 95% CI 1.08-2.35) type 2 diabetes compared to controlled diabetes (OR 1.13; 95% CI 0.94 to 1.36). The positive association was driven by proximal (OR 1.35; 95% CI 1.03 to 1.77) and distal (OR 1.67; 95% CI 1.30 to 2.15) colon cancer but not rectal cancer.ConclusionsIndividuals with type 2 diabetes have a higher risk of early-onset CRC, with stronger associations for uncontrolled/complicated diabetes. The rising prevalence of type 2 diabetes among younger adults in the US may partially contribute to the increasing incidence of early-onset CRC.

A large fraction of heterochromatin in the metazoan genome is associated with the nuclear lamina (NL) in interphase nuclei. This heterochromatin is often referred to as Lamina-Associated Domains (LADs) and are often mapped from cell populations asynchronously progressing through the cell cycle. We and others have recently reported that LADs are largely stable during G1, S, or G2 phases of the cell cycle, and appear similar to LADs mapped from bulk cell populations. LADs in senescent cells, however, are reported to be quite different from proliferating cells, and it remains unclear how senescent cell LADs are established. As cells finish mitosis and re-enter G1, reassembly of the nuclear envelope and NL appears to precede mitotic chromosome decondensation. Therefore, the initial NL interactions with the decondensing chromatin may be quite different from those reported in asynchronous or FACS isolated G1, S, or G2 populations. By developing a modified version of the Tyramide-Signal Amplification sequencing (TSA-seq), which we call chromatin pull down-based Tyramide Signal Amplification-sequencing (cTSA-seq), we uncover a dynamic NL-chromatin interaction as cells progress through G1. The appearance of stable LADs coincides with sufficient chromatin decondensation and active gene expression in G1. Interestingly, early G1 NL-chromatin interactions, which are found toward the telomeric ends of human chromosomes, are similar to those found in oncogene-induced senescent cells. We find that the assembly of LADs during the formation of the G1 nucleus is gradual and that the arrest of NL-chromatin interactions in early G1 may contribute to genome disorganization of senescence cells.

BackgroundCOVID-19 is a new and highly contagious respiratory disease that has caused global spread, high case fatality rate in severe patients, and a huge medical burden due to invasive mechanical ventilation. The current diagnosis and treatment guidelines are still need to be improved, and more excellent clinical experience is needed to provide reference.MethodsWe analyzed and summarized clinical data of 97 confirmed COVID-19 adult patients (including 26 severe cases) admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, 2020 to March 10, 2020, included laboratory examination results, imaging findings, treatment effect, prognosis, etc, in order to put forward prediction index of severe COVID-19 patients, principles of early intervention and methylprednisolone usages in COVID-19 patients.ResultsHypoxemia, hyperlactic acid, hypoproteinemia, and hypokalemia were prevalent in COVID-19 patients. The significant low lymphocyte count, hypoproteinemia, hypokalemia, the persistent or worsen high CRP, high D-dimer, and high BNP, and the occurrence of hemoptysis and novel coronavirus (SARS-CoV-2) viremia were important indicators for early diagnosis and prediction of severe disease progression.Characteristic images of lung CT had a clear change in COVID-19, Ground-glass opacity (GGO) and high-density linear combinations may indicate different pathological changes. Rapid lobular progression of GGO suggests the possibility of severe disease.Basic principles of early intervention treatment of COVID-19: on the premise of no effective antiviral drugs, treatment is based on supportive and symptomatic therapy (albumin supplementation, supplement of potassium, supplement blood plasma, etc.) in order to maintain the stability of the intracellular environment and adequately reactivate body immunity to clean up SARS-CoV-2.According to severity, oxygenation index, body weight, age, underlying diseases, appropriate amount methylprednisolone application on severe/critical COVID-19 patients on demand, improved blood oxygen and reduced the utilization rate of invasive mechanical ventilation, case fatality rate and medical burden significantly. The most common indications for invasive mechanical ventilation should be strictly control in critical COVID-19 patients.ConclusionsAccurate and timely identification of clinical features in severe risks, and early and appropriate intervention can block disease progression. 2. Appropriate dose of methylprednisolone can effectively avoid invasive mechanical ventilation and reduce case fatality rate in critical COVID-19 patients.

BackgroundSince December 2019, Coronavirus Disease 2019 (COVID-19) emerged in Wuhan city and rapidly spread throughout China. The mortality of novel coronavirus pneumonia (NCP) in severe and critical cases is very high. Facing this kind of public health emergency, high efficient administrative emergency responsive mode in designated hospital is needed.MethodAs an affiliated hospital of Sun Yat-sen University, our hospital is the only designated one for diagnosis and treatment of COVID-19 in Zhuhai, a medium-sized city. Novel coronavirus pneumonia department, which is administrative led by the president of hospital directly, has been established at early stage of epidemic crisis in my hospital. In NCP department, there are core members of Pulmonary and Critical Care Medicine (PCCM) specialist and multidisciplinary team. Don’t stick to national guidelines of NCP, based on professional opinion by respiratory professor and expert group, we focused on individualized treatment and timely adjustment of treatment and management strategies in working about COVID-19 patients.Results1. High working efficiency: By Mar 02, 2020, we have completed 2974 citywide consultations and treatment of 366 inpatients, including 101 patients diagnosed with COVID-19. 2. Excellent therapeutic effect: Among 101 hospitalized patients with confirmed COVID-19, all were cured and discharged, except for one death. No secondary hospital infection, no pipeline infection and no pressure sore were found in all patients. 3. Finding and confirming person-to-person transmission characteristic of COVID-19 prior to official release conference: Strengthened protection is key point to zero infection in healthcare group and medical faculty and lower rate of second generation infectious patients. 4. Timely adjustment management and treatment strategy prior to guideline update: The first evidence of digestive tract involvement in COVID-19 has been found, and the earliest clinical trial of chloroquine in the treatment of COVID-19 has been carried out in our hospital.ConclusionsIn our hospital, establishment of NCP department, which is administratively led by the president of hospital directly and specialized conduct by respiratory professor, is the key to success in management and treatment of COVID-19 patients. This hospital emergency responsive mode could provide reference for other hospitals and cities in epidemic situation.

The new coronavirus (SARS-CoV-2) outbreak originating from Wuhan, China, poses a threat to global health. While it’s evident that the virus invades respiratory tract and transmits from human to human through airway, other viral tropisms and transmission routes remain unknown. We tested viral RNA in stool from 73 SARS-CoV-2-infected hospitalized patients using rRT-PCR. 53.42% of the patients tested positive in stool. 23.29% of the patients remained positive in feces even after the viral RNA decreased to undetectable level in respiratory tract. The viral RNA was also detected in gastrointestinal tissues. Furthermore, gastric, duodenal and rectal epithelia showed positive immunofluorescent staining of viral host receptor ACE2 and viral nucleocapsid protein in a case of SARS-CoV-2 infection. Our results provide evidence for gastrointestinal infection of SARS-CoV-2, highlighting its potential fecal-oral transmission route.

Many hard and soft corals harbor algae for photosynthesis. The algae live inside coral cells in a specialized membrane compartment called symbiosome, which shares the photosynthetically fixed carbon with coral host cells, while host cells provide inorganic carbon for photosynthesis1. This endosymbiotic relationship is critical for corals, but increased environmental stresses are causing corals to expel their endosymbiotic algae, i.e. coral bleaching, leading to coral death and degradation of marine ecosystem2. To date, the molecular pathways that orchestrate algal recognition, uptake, and maintenance in coral cells remain poorly understood. We report chromosome-level genome assembly of a fast-growing soft coral, Xenia species (sp.)3, and its use as a model to decipher the coral-algae endosymbiosis. Single cell RNA-sequencing (scRNA-seq) identified 13 cell types, including gastrodermis and cnidocytes, in Xenia sp. Importantly, we identified the endosymbiotic cell type that expresses a unique set of genes implicated in the recognition, phagocytosis/endocytosis, maintenance of algae, and host coral cell immune modulation. By applying scRNA-seq to investigate algal uptake in our new Xenia sp.. regeneration model, we uncovered a dynamic lineage progression from endosymbiotic progenitor state to mature endosymbiotic and post-endosymbiotic cell states. The evolutionarily conserved genes associated with the endosymbiotic process reported herein open the door to decipher common principles by which different corals uptake and expel their endosymbionts. Our study demonstrates the potential of single cell analyses to examine the similarities and differences of the endosymbiotic lifestyle among different coral species.

SummaryCellular architectural proteins often participate in organ development and maintenance. Although functional decay of some of these proteins during aging is known, the cell-type specific developmental role and the cause and consequence of their subsequent decay remain to be established especially in mammals. By studying lamins, the nuclear structural proteins, we demonstrate that lamin-B1 functions specifically in the thymic epithelial cells (TECs) for proper thymus organogenesis. An upregulation of proinflammatory cytokines in the intra-thymic myeloid immune cells during aging accompanies a gradual reduction of adult TEC lamins-B1. These cytokines cause adult TEC senescence and lamin-B1 reduction. We identify 17 adult TEC subsets and show that TEC lamin-B1 maintains the composition of these TECs. Lamin-B1 supports the expression of TEC genes needed for maintaining adult thymic architecture and function. Thus, structural proteins involved in organ building and maintenance can undergo inflammation-driven decay which can in turn contribute to age-associated organ degeneration.