Role of gut microbiota in Crohn's disease pathogenesis: Insights from fecal microbiota transplantation in mouse model.

BACKGROUND: Inflammatory bowel disease, particularly Crohn's disease (CD), has been associated with alterations in mesenteric adipose tissue (MAT) and the phenomenon termed "creeping fat". Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD, with these tissues characterized by inflammation and fibrosis. AIM: To evaluate the complex interplay among MAT, creeping fat, inflammation, and gut microbiota in CD. METHODS: Intestinal tissue and MAT were collected from 12 patients with CD. Histological manifestations and protein expression levels were analyzed to determine lesion characteristics. Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice. The intestinal and mesenteric lesions in these mice, as well as their systemic inflammatory status, were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects. RESULTS: Pathological examination of MAT showed significant differences between CD-affected and unaffected colons, including significant differences in gut microbiota structure. Fetal microbiota transplantation (FMT) from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD ameliorated CD symptoms, whereas FMT from CD patients into these mice exacerbated CD symptoms. Notably, FMT influenced intestinal permeability, barrier function, and levels of proinflammatory factors and adipokines. Furthermore, FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD. CONCLUSION: Gut microbiota play a critical role in the histopathology of CD. Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.

[Expression of the D930020B18Rik gene in the mouse testis during spermatogenesis: Characteristics and potential role].

OBJECTIVE: To investigate the expression pattern of the D930020B18Rik gene in the testis of the mouse in different stages of development and its possible role in spermatogenesis. METHODS: Using gene expression profile microarray, we identified highly expressed D930020B18Rik in the mouse testis and analyzed the expression pattern of the gene by qPCR, immunohistochemistry, Western blot and immunofluorescence staining, and verified its function and molecular mechanism using bioinformatics analysis, dual-luciferase reporter assay and cell cycle synchronization. RESULTS: The expression of the D930020B18Rik gene remained low in the testis of the mouse and mainly localized in the cytoplasm of spermatogonia during the first 2 postnatal weeks (PNW), increased from the 3rd PNW to sexual maturity, localized in the cytoplasm of spermatogonia and the nuclei of round and elongated spermatids, but was absent in the nuclei of mature sperm. Phylogenetic analysis showed that the D930020B18Rik protein sequence was highly conserved in mammals. Gene set enrichment analysis indicated that D930020B18Rik and its homologous protein might be involved in regulating spermatogenesis of mammals by participating in nucleoplasmic condensation (normalized enrichment score ï¼»NESï¼½ = 1.652, P < 0.01, false discovery rate ï¼»FDRï¼½ = 0.153), meiosis (NES = 1.960, P < 0.01, FDR = 0.001) and formation of microtubule cytoskeleton during mitosis (NES = 1.903, P < 0.01, FDR = 0.009). Dual-luciferase reporter assay revealed that the transcription factors klf5 and foxo1 could identify and bind D930020B18Rik promoters and perform the function of positive or negative transcriptional regulation. CONCLUSION: The D930020B18Rik gene is expressed in the mouse testis in a time- and location-specific manner, highly associated with spermiogenesis, mainly localized in the nuclei of germ cells, and may be involved in the meiosis of spermatocytes and spermiogenesis.

Hydrogels containing KYNA promote angiogenesis and inhibit inflammation to improve the survival rate of multi-territory perforator flaps.

BACKGROUND: A new spray adhesive (KYNA-PF127) was established through the combination of thermosensitive hydrogel (Pluronic F127) and KYNA, aimed to investigate the effect of KYNA-PF127 on multi-territory perforator flaps and its possible molecular mechanism. MATERIALS AND METHODS: 36 SD male rats with 250-300 g were randomly divided into 3 groups (n = 12): control group, blank glue group and KYNA-PF127 group. KYNA-PF127 hydrogel was prepared and characterized for its morphology and properties using scanning electron microscopy. CCK-8 assay, scratch wound assay, transwell assay, tube formation assay and Ki67 staining were used to study the effect of KYNA-PF127 on the proliferation, migration, and tube formation of HUVECs. VEGF and FGF2 were measured by qPCR to evaluate the angiogenesis capacity of HUVECs in vitro. In vivo, the effect of each group on the survival area of the cross-zone perforator flap was evaluated, and angiogenesis was evaluated by HE and immunofluorescence (CD31 and MMP-9). The effect of inflammation on skin collagen fibers was assessed by Masson. Immunohistochemistry (SOD1, IL-1ß, TNF-α) was used to evaluate the effects of oxidative stress and inflammatory factors on multi-territory flaps. RESULTS: KYNA-PF127 has good sustained release and biocompatibility at 25% concentration. KYNA-PF127 promoted the proliferation, migration, and angiogenesis of HUVECs in vitro. In vivo, the survival area of multi-territory perforator flaps and angiogenic capability have increased after KYNA-PF127 intervention. KYNA-PF127 could effectively reduce the oxidative stress and inflammation of multi-territory perforator flaps. CONCLUSION: KYNA-PF127 promotes angiogenesis through its antioxidant stress and anti-inflammatory effects, and shows potential clinical value in promoting the survival viability and drug delivery of multi-territory perforator flaps.

Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor.

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins, showing a potential threat to humans. Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus, PCoV-GX/P2V, which was isolated from a Malayan pangolin (Manis javanica). PCoV-GX/P2V could grow in human hepatoma, colorectal adenocarcinoma cells, and human primary nasal epithelial cells. It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2 (hACE2) as SARS-CoV-2 did. After intranasal inoculation to the hACE2-transgenic mice, PCoV-GX/P2V not only replicated in nasal turbinate and lungs, but also caused interstitial pneumonia, characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage. Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection. These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.

Surgical management of duodenal Crohn's disease.

BACKGROUND: The case of Crohn's disease involving the duodenum is rare, and its surgical management requires a thorough understanding. AIM: To investigate the surgical management of duodenal Crohn's disease. METHODS: We systematically reviewed patients diagnosed with duodenal Crohn's disease who underwent surgery in the Department of Geriatrics Surgery of the Second Xiangya Hospital of Central South University from January 1, 2004, to August 31, 2022. The general information, surgical procedures, prognosis, and other information of these patients were collected and summarized. RESULTS: A total of 16 patients were diagnosed with duodenal Crohn's disease, where 6 cases had primary duodenal Crohn's disease, and 10 had secondary duodenal Crohn's disease. Among patients with primary disease, 5 underwent duodenal bypass and gastrojejunostomy, and 1 received pancreaticoduodenectomy. Among those with a secondary disease, 6 underwent closure of duodenal defect and colectomy, 3 received duodenal lesion exclusion and right hemicolectomy, and 1 underwent duodenal lesion exclusion and double-lumen ileostomy. CONCLUSION: Crohn's disease involving the duodenum is a rare condition. Different surgical management should be applied for patients with Crohn's disease presenting with different clinical manifestations.

Continuous evolution and emerging lineage of seasonal human coronaviruses: A multicenter surveillance study.

The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.

The dynamics of coordination patterns in multiteam systems response to emergency: Case study from a pharmaceutical enterprise.

Effective coordination of multiteam systems (MTSs) can help enterprises respond quickly to complex and uncertain problems under disasters. However, it is unclear how MTS coordination patterns dynamically affect MTS performance in disasters. This study examined how MTSs responded to an emergency production incident at the Zhejiang Huisong Pharmaceutical Company in China during the COVID-19 pandemic through a qualitative and quantitative study. Based on social network theory, we found that a centralized coordination pattern impacts MTS performance by giving play to the leadership team's network centrality position advantage during the crisis outbreak period. In the post-crisis period, the decentralized coordination pattern impacts MTS performance by giving play to the advantages of horizontal coordination. Our results help managers to consider the dynamics of coordination patterns in crisis management in ways that assist them in adapting an effective coordination pattern to changing and uncertain operational conditions.

The effect of horticultural therapy on depressive symptoms among the elderly: A systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to assess the effectiveness of horticultural therapy on depressive symptoms in the elderly and determine the potential moderators of the intervention effect. Methods: In early June 2022, randomized controlled trials and Quasi-experimental studies were searched on Web of Science, PsycINFO, CINAHL, EMBASE, Medline, PubMed, CNKI, WANFANG DATA, and CQVIP. Three independent authors proposed the following inclusion criterion for this study: the elderly with applied horticultural therapy intervention compared to non-HT intervention. From a total of 3,068 records, only 34 studies met the inclusion criteria. After the full-text screening, 13 studies were included in the analysis. An assessment of the risk of bias was conducted using RoBINS-I and RoB 2 tools. The comprehensive Meta-Analysis 3.3 tool was used for the meta-analysis. Results: Meta-analysis suggested that mean depression scores of elderly people who underwent horticultural therapy intervention were significantly lower than those who did not receive HT therapy. More significant effects were found for the elderly with mean age equal to or over 75 years instead of younger than 75 years, in randomized controlled trials instead of quasi-experimental studies, for studies with more than 20 participants receiving horticultural therapy at the same time and place instead of equal to or fewer than 20 horticultural therapy participants. Conclusions: This evidence supported that horticultural therapy had a significant positive effect on the depressive symptoms outcomes for the elderly. Therefore, our data revealed that horticultural therapy could be considered as a part of therapy in depressive symptoms reduction programs. Due to the high degree of heterogeneity and the limited number of studies, a future review is warranted to determine the effects of horticultural therapy on depressive symptoms reduction in the elderly. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=272464, identifier: CRD42021272464.

Natural infection of pangolins with human respiratory syncytial viruses.

Respiratory syncytial virus (RSV) is an enveloped non-segmented negative sense RNA virus that belongs to Orthopneumovirus genus of the Pneumoviridae family in the order Mononegavirales. The virus is the leading cause of severe respiratory disease in children under two years of age and is responsible for substantial disease burden in infants and elder people in both developed and developing countries1,2. RSV is only known to circulate among humans, though it was first isolated from chimpanzees3. The virus can experimentally infect mice, rats, cotton rats, ferrets, and hamsters, but does not naturally circulate in these animal populations4. We found that Malayan pangolins (Manis javanica) were naturally infected with RSVs that have 99.4-99.8% genomic identity with strains circulating in humans. Phylogenetic analyses revealed that five RSVs in pangolins were RSV-A ON1 and seven were RSV-B BA genotypes, both of which are currently prevalent in humans worldwide. These findings suggest that humans might transmit their viruses to endangered wildlife.

Weather and Birth Weight: Different Roles of Maternal and Neonatal GPR61 Promoter Methylation.

Objectives: It is unclear whether G protein-coupled receptor 61 (GPR61) affecting body weight, plays a role in the association between birth weight and weather. This study aimed to assess the effects of prenatal weather and GPR61 on birth weight. Methods: A total of 567 mother-newborn pairs were recruited in Houzhai Center Hospital during 2011-2012. We detected the maternal and neonatal GPR61 promoter methylation levels, and obtained meteorological and air pollution data. Results: A positive association was observed between maternal and neonatal GPR61 methylation levels, and both of them were affected by precipitation, relative humidity (RH) and daily temperature range (DTR). Birth weight was associated negatively with RH and positively with DTR ( P < 0.05). A significant association was observed between birth weight and neonatal GPR61 methylation. We observed that maternal GPR61 methylation seemed to modify associations between weather and birth weight ( P interaction < 0.10), while neonatal GPR61 methylation mediated the effects of RH and DTR on birth weight ( P < 0.05). Conclusions: Our findings revealed the significant associations among prenatal weather, GPR61 methylation and birth weight. Maternal GPR61 methylation may modify the susceptibility of birth weight to prenatal weather conditions, while neonatal GPR61 methylation may be a bridge of the effects of prenatal RH and DTR on birth weight.

Potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non-small cell lung cancer patients.

GROWING EFFORTS ARE BEING INVESTED IN INVESTIGATING VARIOUS MOLECULAR APPROACHES TO DETECT MINIMAL RESIDUAL DISEASE (MRD) AND PREDICT DISEASE RECURRENCE. IN OUR STUDY, WE INVESTIGATED THE UTILITY OF PARALLEL LONGITUDINAL ANALYSIS OF MUTATION AND DNA METHYLATION PROFILES FOR PREDICTING MRD IN POSTOPERATIVE NON-SMALL-CELL LUNG CANCER (NSCLC) PATIENTS. TUMOR TISSUES AND LONGITUDINAL BLOOD SAMPLES WERE OBTAINED FROM 65 PATIENTS WITH RESECTED STAGE IA-IIIB NSCLC. SOMATIC MUTATION AND DNA METHYLATION PROFILING WERE PERFORMED USING ULTRA-DEEP TARGETED SEQUENCING AND TARGETED BISULFITE SEQUENCING, RESPECTIVELY. DYNAMIC CHANGES IN PLASMA-BASED MUTATION AND TUMOR-INFORMED METHYLATION PROFILES, REFLECTED AS MRD SCORE, WERE OBSERVED FROM BEFORE SURGERY (BASELINE) TO POSTOPERATIVE FOLLOW-UP, REFLECTING THE DECREASE IN TUMOR BURDEN OF THE PATIENTS WITH RESECTED NSCLC. MUTATIONS WERE DETECTED FROM PLASMA SAMPLES IN 63% OF THE PATIENTS AT BASELINE, WHICH SIGNIFICANTLY REDUCED TO 23-25% DURING POST-OPERATIVE FOLLOW-UPS. MRD SCORE POSITIVE RATE WAS 95.7% AT BASELINE, WHICH REDUCED TO 74% AT THE FIRST AND 70% AT THE SECOND FOLLOW-UP. AMONG THE 5 RELAPSED PATIENTS WITH PARALLEL LONGITUDINAL ANALYSIS OF MUTATION AND METHYLATION PROFILE, ELEVATED MRD SCORE WAS OBSERVED AT FOLLOW-UP BETWEEN 0.5-7 MONTHS PRIOR TO RADIOLOGIC RECURRENCE FOR ALL 5 PATIENTS. OF THEM, 4 PATIENTS ALSO HAD CONCOMITANT INCREASE IN ALLELIC FRACTION OF MUTATIONS IN AT LEAST 1 FOLLOW-UP TIME POINT, BUT ONE PATIENT HAD NO MUTATION DETECTED THROUGHOUT ALL FOLLOW-UPS. OUR RESULTS DEMONSTRATE THAT LONGITUDINAL PROFILING OF MUTATION AND DNA METHYLATION MAY HAVE POTENTIAL FOR DETECTING MRD AND PREDICTING RECURRENCE IN POSTOPERATIVE NSCLC PATIENTS.

The complete chloroplast genome of Carex agglomerata C. B. Clarke (Cyperaceae), an endemic species from China.

Carex agglomerata C. B. Clarke is a sedge with excellent ornamental characters, it is an important ecosystem stabilizer. Here we report the complete chloroplast genome of C. agglomerata to provide a foundation for further phylogenetic studies on the Cyperaceae. The chloroplast (cp) genome is 184,157 bp in size and consists of a large single-copy (LSC) region 106,654 bp in length, a small single-copy (SSC) region of 36,099 bp, two inverted repeats (IR) regions each 20,702 bp. The total GC content of the cp genome is 33.9% with the LSC, SSC, and IR regions 32, 32.5, and 42.9%, respectively. The cp genome contains 128 genes, including 80 protein-coding, 40 tRNA, and eight rRNA genes. The phylogenetic analysis showed C. agglomerata is in a clade with Carex neurocarpa Maxim and Carex siderosticta Hance. This study provides a basis for further phylogenetic studies of Carex.

Ailanthus Altissima-derived Ailanthone enhances Gastric Cancer Cell Apoptosis by Inducing the Repression of Base Excision Repair by Downregulating p23 Expression.

Chemotherapy plays an irreplaceable role in the treatment of GC, but currently available chemotherapeutic drugs are not ideal. The application of medicinal plants is an important direction for new drug discovery. Through drug screening of GC organoids, we determined that ailanthone has an anticancer effect on GC cells in vitro and in vivo. We also found that AIL can induce DNA damage and apoptosis in GC cells. Further transcriptome sequencing of PDX tissue indicated that AIL inhibited the expression of XRCC1, which plays an important role in DNA damage repair, and the results were also confirmed by western blotting. In addition, we found that AIL inhibited the expression of P23 and that inhibition of P23 decreased the expression of XRCC1, indicating that AIL can regulate XRCC1 via P23. The results of coimmunoprecipitation showed that AIL can inhibit the binding of P23 and XRCC1 to HSP90. These findings indicate that AIL can induce DNA damage and apoptosis in GC cells. Meanwhile, AIL can decrease XRCC1 activity by downregulating P23 expression to inhibit DNA damage repair. The present study sheds light on the potential application of new drugs isolated from natural medicinal plants for GC therapy.

METTL16 promotes cell proliferation by up-regulating cyclin D1 expression in gastric cancer.

N6-methyladenosine (m6A) is a well-known modification of RNA. However, as a key m6A methyltransferase, METTL16 has not been thoroughly studied in gastric cancer (GC). Here, the biological role of METTL16 in GC and its underlying mechanism was studied. Immunohistochemistry was used to detect the expression of METTL16 and relationship between METTL16 level and prognosis of GC was analysed. CCK8, colony formation assay, EdU assay and xenograft mouse model were used to study the effect of METTL16. Regulatory mechanism of METTL16 in the progression of GC was studied through flow cytometry analysis, RNA degradation assay, methyltransferase inhibition assay, RT-qPCR and Western blotting. METTL16 was highly expressed in GC cells and tissues and was associated with prognosis. In vitro and in vivo experiments confirmed that METTL16 promoted proliferation of GC cells and tumour growth. Furthermore, down-regulation of METTL16 inhibited proliferation by G1/S blocking. Significantly, we identified cyclin D1 as a downstream effector of METTL16. Knock-down METTL16 decreased the overall level of m6A and the stability of cyclin D1 mRNA in GC cells. Meanwhile, inhibition of methyltransferase activity reduced the level of cyclin D1. METTL16-mediated m6A methylation promotes proliferation of GC cells through enhancing cyclin D1 expression.

Effects of Outdoor Temperature on Blood Pressure in a Prospective Cohort of Northwest China.

OBJECTIVE: The relationship between outdoor temperature and blood pressure (BP) has been inconclusive. We analyzed data from a prospective cohort study in northwestern China to investigate the effect of outdoor temperature on BP and effect modification by season. METHODS: A total of 32,710 individuals who participated in both the baseline survey and the first follow-up in 2011-2015 were included in the study. A linear mixed-effect model and generalized additive mixed model (GAMM) were applied to estimate the association between outdoor temperature and BP after adjusting for confounding variables. RESULTS: The mean differences in systolic blood pressure (SBP) and diastolic blood pressure (DBP) between summer and winter were 3.5 mmHg and 2.75 mmHg, respectively. After adjusting for individual characteristics, meteorological factors and air pollutants, a significant increase in SBP and DBP was observed for lag 06 day and lag 04 day, a 0.28 mmHg (95% CI: 0.27-0.30) per 1 °C decrease in average temperature for SBP and a 0.16 mmHg (95% CI: 0.15-0.17) per 1 °C decrease in average temperature for DBP, respectively. The effects of the average temperature on both SBP and DBP were stronger in summer than in other seasons. The effects of the average temperature on BP were also greater if individuals were older, male, overweight or obese, a smoker or drinker, or had cardiovascular diseases (CVDs), hypertension, and diabetes. CONCLUSIONS: This study demonstrated a significant negative association between outdoor temperature and BP in a high-altitude environment of northwest China. Moreover, BP showed a significant seasonal variation. The association between BP and temperature differed by season and individuals' demographic characteristics (age, gender, BMI), unhealthy behaviors (smoking and alcohol consumption), and chronic disease status (CVDs, hypertension, and diabetes).

Inhibition of long noncoding RNA MALAT1 suppresses high glucose-induced apoptosis and inflammation in human umbilical vein endothelial cells by suppressing the NF-κB signaling pathway.

The study investigated the expression of long noncoding RNA (lncRNA) MALAT1 in high glucose (HG)-induced human vascular endothelial cells (HUVECs) and the role of MALAT1 in the apoptosis of HG-induced HUVECs. The HUVECs were cultured and induced with 25 mmol/L HG. After that, the HUVECs were transfected with MALAT1 siRNA. The expression levels of MALAT1 were detected with qPCR, whereas the expression levels of Bax, Bcl-2, cleaved-caspase-3, cleaved-caspase-9, p-65, and p-p65 were detected using Western blot. The roles of MALAT1 in cell activities, including apoptosis, were evaluated using the CCK-8 assay, TUNEL staining, and flow cytometry. The expression levels of inflammatory factors (TNF-α and IL-6) were measured using ELISA. The expression levels of MALAT1, TNF-α, and IL-6 in HUVECs were increased in the HG environment; however, when MALAT1 was silenced in the HUVECs, cell proliferation increased significantly, the expression levels of TNF-α, IL-6, Bax, cleaved-caspase-3, and cleaved-caspase-9 decreased, and the rate of apoptosis also decreased. Silencing MALAT1 inhibited the expression of p-p65 in HG-induced HUVECs. In conclusion, our study demonstrated that MALAT1 is upregulated in HG-induced HUVECs, and inhibition of MALAT1 inhibits HG-induced apoptosis and inflammation in HUVECs by suppression of the NF-κB signaling pathway.

Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins.

The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.