The role of self-efficacy and self-care agency as mediating factors in the link between health literacy and health-promoting lifestyle among older adults post covid 19 era: A multiple mediator model.

Health-promoting lifestyle is poor in older adults during COVID-19 pandemic. Elucidate the underlying mechanisms between health literacy and health-promoting lifestyle is important. Therefore, we investigated the mediating effect of self-efficacy and self-care agency in relation between health literacy and health-promoting lifestyle among older adults post covid 19 era. A cross-sectional descriptive survey on 200 older adults with the mean age of 68.3 were recruited from Lecai urban community in China, through convenience sampling. Information was assessed using Health literacy Assessment Scale for Infectious Diseases of Chinese Residents, the General Self Efficacy Scale, Chinese version of the Elderly Self-care Ability Scale, and the Health-Promoting Lifestyle Profile-Chinese Elderly. A serial multiple mediation modeling was tested using the PROCESS macro for SPSS to validate the pathways. Results indicated that positive correlations were found between health literacy, self-efficacy, self-care agency and health-promoting lifestyle in older adults. Meanwhile, health literacy was linked to enhanced health-promoting lifestyle through two pathways: (1) self-efficacy; (2) chain combination of self-efficacy and self-care agency. Self-efficacy and self-care agency mediated the relationship between health literacy and health-promoting lifestyle in older adults. Therefore, attention to improving self-efficacy, self-care agency and health literacy should be considered crucial for improving health-promoting lifestyle.

Validity and reliability of upper extremity star excursion balance test in adolescent swimmers.

Background: Upper limb balance is one of the important physical fitness parameters for all populations, especially overhead athletes like swimmers. Upper extremity star excursion balance test (UESEBT) is a comprehensive dynamic balance assessment, this study aims to explore the reliability and validity of UESEBT among adolescent swimmers. Methods: This cross-sectional study recruited 70 adolescent swimmers. All participants were required to complete UESEBT, upper quarter Y-balance test (UQYBT), maximal isometric strength (MIS) tests in upper limb, closed kinetic chain upper extremity stability test (CKCUEST), trunk flexor endurance test (TFET) and lateral trunk endurance test (LTET). The intra- and inter-operator reliability and the correlation of UESEBT with other physical performances were conducted. Results: For reliability, the intra- and inter-operator reliability of all directions and composite score were high-to-excellent (ICC = 0.706-1.000) among all participants. For validity, the UESEBT has a moderate-to-strong correlation with UQYBT (r = 0.42-0.72, p < 0.001), and a weak-to moderate one with CKCUEST (r = 0.25-0.42, p < 0.05). Furthermore, the UESEBT performance showed weak-to-moderate correlations with MIS (r = 0.24-0.44, p < 0.05). UESEBT was correlated to LTET (r = 0.24-0.33, p < 0.05) whereas no relationship was found with TFET. Conclusions: UESEBT was a reliable and valid tool to screen upper extremity dynamic balance among adolescent swimmers. UESEBT provides more detailed information in eight directions to assess the upper limb sport performance. Further study should explore the prediction ability of UESEBT for injury.

A structural equation model linking health literacy, self efficacy and quality of life in adults with coronary heart disease.

BACKGROUND: Cardiovascular disease is the world major cause of death. There is sufficient evidence that patients with coronary heart disease (CHD) experience poor quality of life. Health literacy and self efficacy are modifiable psychosocial factors that could affect quality of life, and these factors should be considered as targets for intervention. As the relationships among health literacy, self efficacy, and quality of life in the CHD population have not been well understood. Thus, we constructed the structure equation model in these valuables. METHODS: A cross-sectional study of a convenience sample among 200 patients with CHD were participated from outpatient clinics in three tertiary general hospitals in Baoding City in mainland China, from December 2018 to June 2019. Data regarding demographic features, health literacy, self efficacy and quality of life were assessed. A structure equation model was used to construct and validate the pathways. RESULTS: The mean age of the study sampled patients was 65.37 years old. The average level of health literacy, self efficacy and quality of life were 9.6 ± 3.5, 28.8 ± 13.9 and 381.8 ± 130.1 respectively. Significant associations were observed from health literacy to quality of life, and self efficacy played a partial mediating role between health literacy and quality of life in the CHD population. Health literacy and self efficacy explained for 59.6% of the variance in quality of life. CONCLUSIONS: Health literacy had a direct influence on quality of life, and an indirect influence on quality of life via self efficacy in the patients with CHD.

Human Immunodeficiency Virus-Associated Exosomes Promote Kaposi's Sarcoma-Associated Herpesvirus Infection via the Epidermal Growth Factor Receptor.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causal agent for Kaposi's sarcoma (KS), the most common malignancy in people living with human immunodeficiency virus (HIV)/AIDS. The oral cavity is a major route for KSHV infection and transmission. However, how KSHV breaches the oral epithelial barrier for spreading to the body is not clear. Here, we show that exosomes purified from either the saliva of HIV-positive individuals or the culture supernatants of HIV-1-infected T-cell lines promote KSHV infectivity in immortalized and primary human oral epithelial cells. HIV-associated saliva exosomes contain the HIV trans-activation response element (TAR), Tat, and Nef RNAs but do not express Tat and Nef proteins. The TAR RNA in HIV-associated exosomes contributes to enhancing KSHV infectivity through the epidermal growth factor receptor (EGFR). An inhibitory aptamer against TAR RNA reduces KSHV infection facilitated by the synthetic TAR RNA in oral epithelial cells. Cetuximab, a monoclonal neutralizing antibody against EGFR, blocks HIV-associated exosome-enhanced KSHV infection. Our findings reveal that saliva containing HIV-associated exosomes is a risk factor for the enhancement of KSHV infection and that the inhibition of EGFR serves as a novel strategy for preventing KSHV infection and transmission in the oral cavity.IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) is the causal agent for Kaposi's sarcoma (KS), the most common malignancy in HIV/AIDS patients. Oral transmission through saliva is considered the most common route for spreading the virus among HIV/AIDS patients. However, the role of HIV-specific components in the cotransfection of KSHV is unclear. We demonstrate that exosomes purified from the saliva of HIV-positive patients and secreted by HIV-infected T-cell lines promote KSHV infectivity in immortalized and primary oral epithelial cells. HIV-associated exosomes promote KSHV infection, which depends on HIV trans-activation response element (TAR) RNA and EGFR of oral epithelial cells, which can be targeted for reducing KSHV infection. These results reveal that HIV-associated exosomes are a risk factor for KSHV infection in the HIV-infected population.

The molecular landscape of synchronous colorectal cancer reveals genetic heterogeneity.

Synchronous colorectal cancers (syCRCs), which present two or more lesions at diagnosis, are rare and pose a great challenge for clinical management. Although some predisposing factors associated with syCRCs have been studied with limited accession, the full repertoire of genomic events among the lesions within an individual and the causes of syCRCs remain unclear. We performed whole-exome sequencing of 40 surgical tumour samples of paired lesions from 20 patients to characterize the genetic alterations. Lesions from same patient showed distinct landscapes of somatic aberrations and shared few mutations, which suggests that they originate and develop independently, although they shared the similar genetic background. Canonical genes, such as APC, KRAS, TP53 and PIK3CA, were frequently mutated in the syCRCs, and most of them show different mutation profile compared with solitary colorectal cancer. We identified a recurrent somatic alteration (K15fs) in RPL22 in 25% of the syCRCs. Functional analysis indicated that mutated RPL22 may suppress cell apoptosis and promote the epithelial-mesenchymal transition (EMT). Potential drug targets were identified in several signalling pathways, and they present great discrepancy between lesions from the same patient. Our data show that the syCRCs within the same patient present great genetic heterogeneity, and they may be driven by distinct molecular events and develop independently. The discrepancy of potential drug targets and mutation burden in lesions from one patient provides valuable information in clinical management for patients with syCRCs.

Short-chain fatty acids from periodontal pathogens suppress histone deacetylases, EZH2, and SUV39H1 to promote Kaposi's sarcoma-associated herpesvirus replication.

UNLABELLED: Periodontal pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum produce five different short-chain fatty acids (SCFAs) as metabolic by-products. We detect significantly higher levels of SCFAs in the saliva of patients with severe periodontal disease. The different SCFAs stimulate lytic gene expression of Kaposi's sarcoma-associated herpesvirus (KSHV) dose dependently and synergistically. SCFAs inhibit class-1/2 histone deacetylases (HDACs) and downregulate expression of silent information regulator-1 (SIRT1). SCFAs also downregulate expression of enhancer of zeste homolog2 (EZH2) and suppressor of variegation 3-9 homolog1 (SUV39H1), which are two histone N-lysine methyltransferases (HLMTs). By suppressing the different components of host epigenetic regulatory machinery, SCFAs increase histone acetylation and decrease repressive histone trimethylations to transactivate the viral chromatin. These new findings provide mechanistic support that SCFAs from periodontal pathogens stimulate KSHV replication and infection in the oral cavity and are potential risk factors for development of oral Kaposi's sarcoma (KS). IMPORTANCE: About 20% of KS patients develop KS lesions first in the oral cavity, while other patients never develop oral KS. It is not known if the oral microenvironment plays a role in oral KS tumor development. In this work, we demonstrate that a group of metabolic by-products, namely, short-chain fatty acids, from bacteria that cause periodontal disease promote lytic replication of KSHV, the etiological agent associated with KS. These new findings provide mechanistic support that periodontal pathogens create a unique microenvironment in the oral cavity that contributes to KSHV replication and development of oral KS.

HBD-3 induces NK cell activation, IFN-γ secretion and mDC dependent cytolytic function.

We previously showed that human beta defensin-3 (hBD-3) activates mDC via TLR1/2. Here we investigated the effects of hBD-3 on NK cell activation state and effector functions. We observed that hBD-3 activates PBMC to secrete IFN-γ and kill K562 and HUH hepatoma target cells in an NK dependent fashion, and both TLR1/2 and CCR2 are involved. TLR1, TLR2 and CCR2 were expressed on NK cells, and in purified NK culture experiments we observed hBD-3 to directly act on NK cells, resulting in CD69 upregulation and IFNγ secretion. We also observed mDC-hBD-3 enhanced NK cytolytic activity and IFNγ production. These results implicate hBD-3 in its ability to directly activate NK cells and increase NK cell effector function, as well as promote mDC-dependent NK activity. HBD-3 may therefore act as a mediator of innate cell interactions that result in bridging of innate and adaptive immunity.

[Preliminary evaluation on 3-demension changes of facial soft tissue with structure light scanning technique before and after orthognathic surgery of Class III deformities].

OBJECTIVE: To evaluate facial soft tissue 3-deminsion changes of skeletal Class III malocclusion patients after orthognathic surgery using structure light scanning technique. METHODS: Eight patients [3 males and 5 females, aged (27.08 ± 4.42) years] with Class III dentoskeletal relationship who underwent a bimaxillary orthognathic surgical procedure involving advancement of the maxilla by Le Fort I osteotomy and mandibular setback by bilateral sagittal split ramus osteotomy (BSSO) and genioplasty to correct deformity were included. 3D facial images were obtained by structure light scanner for all the patients 2 weeks preoperatively and 6 months postoperatively. The facial soft tissue changes were evaluated in 3-dimension. The linear distances and angulation changes for facial soft tissue landmarks were analyzed. The soft tissue volumetric changes were assessed too. RESULTS: There were significant differences in the sagittal and vertical changes of soft tissue landmarks. The greatest amount of soft tissue change was close to lips. There were more volumetric changes in the chin than in the maxilla, and fewer in the forehead. CONCLUSION: After biomaxillary surgery, there were significant facial soft tissue differences mainly in the sagittal and vertical dimension for skeletal Class III patients. The structure light 3D scanning technique can be accurately used to estimate the soft tissue changes in patients who undergo orthognathic surgery.

Epithelial innate immune response to Acinetobacter baumannii challenge.

Currently, Acinetobacter baumannii is recognized as one of the major pathogens seriously threatening our health care delivery system. Aspects of the innate immune response to A. baumannii infection are not yet well understood. Human ß-defensins (hBDs) are epithelial cell-derived cationic antimicrobial peptides (AMPs) that also function to bridge the innate and adaptive immune system. We tested the induction of hBD-2 and -3 by A. baumannii on primary oral and skin epithelial cells and found that A. baumannii induces hBD-3 transcripts to a greater extent than it induces hBD-2 transcripts on both types of cells. In addition, we found that A. baumannii is susceptible to hBD-2 and -3 killing at submicromolar concentrations. Moreover, hBD-3 induction by A. baumannii was found to be dependent on epidermal growth factor receptor (EGFR) signaling. Inhibition of mitogen-activated protein kinase resulted in reduced expression of both hBD-2 and -3. Lastly, a disintegrin and metalloprotease 17 (ADAM17; also known as TACE) was found to be critical for hBD-3 induction, while ADAM10 and dual oxidase 1 (Duox1) were not required for hBD-3 induction. Induction of AMPs is an important component of innate sensing of pathogens and may play an important role in triggering systemic immune responses to A. baumannii infection. Further studies on the interactions between epithelial cells and A. baumannii will help us understand early stages of infection and may shed light on why some individuals are more vulnerable to A. baumannii infection.

Endovascular Treatment of Transplant Renal Artery Stenosis: A Single-Center Retrospective Cohort Study.

OBJECTIVES: Endovascular therapy is the most common treatment for transplant renal artery stenosis; however, its long-term outcomes remain controversial, with no uniform standard for percutaneous transluminal angioplasty versus percutaneous transluminal stenting. MATERIALS AND METHODS: We retrospectively analyzed 26 patients with transplant renal artery stenosis who underwent endovascular therapy. We evaluated long-term efficacy of endovascular therapy and the reasonable choice of treatment. RESULTS: Serum creatinine increased significantly at onset of transplant renal artery stenosis (113.88 ± 37.573 before vs 279.31 ± 94.98 µmol/L during stenosis; P1 < .001), and endovascular therapy had a good short-term effect (279.31 ± 94.98 during stenosis vs 139.54 ± 124.40 µmol/L at 2 weeks posttreatment; P2 = .002). Long-term efficacy of endovascular therapy was stable (139.54 ± 124.40 at 2 weeks posttreatment vs 150.69 ± 180.72 at 6 months vs 161.58 ± 174.49 µmol/L at last follow-up; P3 > .05). Blood pressure increased significantly at onset of transplant renal artery stenosis (126.65 ± 16.11 before vs 159.62 ± 25.84 mm Hg during stenosis; P1 < .001). Moreover, the short-term effect of endovascular therapy was good (159.62 ± 25.84 during stenosis vs 128.73 ± 14.22 mm Hg at 2 weeks posttreatment; P2 < .001). Long-term effects remained stable (128.73 ± 14.22 at 2 weeks posttreatment vs 131.15 ± 14.55 at 6 months vs 138.50 ± 16.82 mm Hg at last follow-up; P3 > .05). Peak systolic velocity decreased significantly after endovascular therapy (176.6 ± 67.93 during stenosis vs 114.24 ± 67.93 cm/s at 2 weeks posttreatment; P < .001). CONCLUSIONS: Endovascular therapy is effective in transplant renal artery stenosis treatment and has a low incidence of complications. Percutaneous transluminal angioplasty should be performed routinely during endovascular therapy. After dilation, if stenosis remains >25% or retracted, then percutaneous transluminal stenting is recommended. Otherwise, percutaneous transluminal angioplasty is preferred.

Assessing the Relationship Between Gut Microbiota and Posttransplant Diabetes Mellitus.

OBJECTIVES: The incidence of diabetes significantly increases after kidney transplant, and the associated gut microbiota are closely related to diabetes. However, the gut microbiota of recipients with diabetes after kidney transplant remain unexplored. MATERIALS AND METHODS: Feces samples from recipients with diabetes 3 months after kidney transplant were collected and analyzed using high-throughput 16S rRNA gene sequencing. RESULTS: Our study included 45 transplant recipients: 23 posttransplant diabetes mellitus recipients, 11 recipients without diabetes mellitus, and 11 recipients with preexisting diabetes mellitus. No significant differences in intestinal flora richness and α diversity were observed among the 3 groups. However, principal coordinate analysis based on UniFrac distance revealed significant differences in ß diversity. At the phyla level, the abundance of Proteobacteria in posttransplant diabetes mellitus recipients decreased (P = .028), whereas that of Bactericide (P = .004) increased. At the class level, the abundance of Gammaproteobacteria (P = .037) decreased, whereas thatofBacteroidia (P=.004)increased.Attheorderlevel, the abundanceof Enterobacteriales (P = .039)decreased, whereasBacteroidales (P=.004)increased.Atthe family level, the abundance of Enterobacteriaceae (P = .039) and Peptostreptococcaceae (P = .008) decreased, whereas Bacteroidaceae (P = .010) increased. At the genus level,the abundance of Lachnospiraceae incertae sedis (P = .008) decreased, whereas Bacteroides (P = .010) increased. Furthermore, KEGG analysis identified 33 pathways, among which the biosynthesis of unsaturated fatty acids was closely related to gut microbiota and posttransplant diabetes mellitus. CONCLUSIONS: To our knowledge, this is the first comprehensive analysis of the gut microbiota from posttransplant diabetes mellitus recipients. The microbial composition of stool samples of post- transplant diabetes mellitus recipients was significantly different from recipients without diabetes and with preexisting diabetes. The number of bacteria producing short-chain fatty acids decreased, whereas pathogenic bacteria increased.

COVID-19 plasma exosomes promote proinflammatory immune responses in peripheral blood mononuclear cells.

Elevated serum cytokine production in COVID-19 patients is associated with disease progression and severity. However, the stimuli that initiate cytokine production in patients remain to be fully revealed. Virus-infected cells release virus-associated exosomes, extracellular vesicles of endocytic origin, into the blood to deliver viral cargoes able to regulate immune responses. Here, we report that plasma exosomes of COVID-19 patients contain SARS-CoV-2 double stranded RNA (dsRNA) and stimulate robust production of interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and other inflammatory cytokines and chemokines by human peripheral mononuclear cells. Exosome depletion abolished these stimulated responses. COVID-19 plasma exosomes induced proinflammatory responses in CD4+ T cells, CD8+ T cells, and CD14+ monocytes but not significantly in regulatory T cells, Th17 T cells, or central memory T cells. COVID-19 plasma exosomes protect the SARS-CoV-2 dsRNA cargo from RNase and deliver the dsRNA into recipient cells. These exosomes significantly increase expression of endosomal toll-like receptor 3 (TLR3), TLR7, TLR8, and TLR9 in peripheral T cells and monocytes. A pharmacological inhibitor of TLR3 considerably reduced cytokine and chemokine production by CD4+ and CD8+ T cells but not by CD14+ monocytes, highlighting divergent signaling pathways of immune cells in response to COVID-19 plasma exosomes. Our results identify a novel model of intercellular crosstalk following SARS-CoV-2 infection that evoke immune responses positioned to contribute to elevated cytokine production associated with COVID-19 progression, severity, and long-haul symptoms.

TrustGWAS: A full-process workflow for encrypted GWAS using multi-key homomorphic encryption and pseudorandom number perturbation.

The statistical power of genome-wide association studies (GWASs) is affected by the effective sample size. However, the privacy and security concerns associated with individual-level genotype data pose great challenges for cross-institutional cooperation. The full-process cryptographic solutions are in demand but have not been covered, especially the essential principal-component analysis (PCA). Here, we present TrustGWAS, a complete solution for secure, large-scale GWAS, recapitulating gold standard results against PLINK without compromising privacy and supporting basic PLINK steps including quality control, linkage disequilibrium pruning, PCA, chi-square test, Cochran-Armitage trend test, covariate-supported logistic regression and linear regression, and their sequential combinations. TrustGWAS leverages pseudorandom number perturbations for PCA and multiparty scheme of multi-key homomorphic encryption for all other modules. TrustGWAS can evaluate 100,000 individuals with 1 million variants and complete QC-LD-PCA-regression workflow within 50 h. We further successfully discover gene loci associated with fasting blood glucose, consistent with the findings of the ChinaMAP project.

The Toll-like receptor 1/2 agonists Pam(3) CSK(4) and human ß-defensin-3 differentially induce interleukin-10 and nuclear factor-κB signalling patterns in human monocytes.

Human ß-defensin 3 (hBD-3) activates antigen-presenting cells through Toll-like receptors (TLRs) 1/2. Several TLR1/2 agonists have been identified but little is known about how they might differentially affect cellular activation. We compared the effects of hBD-3 with those of another TLR1/2 agonist, Pam(3) CSK(4) , in human monocytes. Monocytes incubated with hBD-3 or Pam(3) CSK(4) produced interleukin-6 (IL-6), IL-8 and IL-1ß, but only Pam(3) CSK(4) induced IL-10. The IL-10 induction by Pam(3) CSK(4) caused down-modulation of the co-stimulatory molecule, CD86, whereas CD86 expression was increased in monocytes exposed to hBD-3. Assessment of signalling pathways linked to IL-10 induction indicated that mitogen-activated protein kinases were activated similarly by hBD-3 or Pam(3) CSK(4) , whereas the non-canonical nuclear factor-κB pathway was only induced by Pam(3) CSK(4) . Our data suggest that the lack of non-canonical nuclear factor-κB signalling by hBD-3 could contribute to the failure of this TLR agonist to induce production of the anti-inflammatory cytokine, IL-10, in human monocytes.

The complete chloroplast genome of Agrimonia pilosa var. nepalensis (D. Don) Nakai.

Agrimonia pilosa var. nepalensis (D. Don) Nakai is an herbaceous species of Rosaceae distributed in China. It has ornamental and ecological values. Lack of genetic background seriously hinders its further research and utilization. To provide genetic information for further study of it, complete chloroplast (cp) genome was characterized in this study. The genome is a circular molecule of 155,147 bp in length with overall GC content of 36.9%, which contains 85 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. It contains a typical tetrad structure, including a large single copy, a small single copy, and two inverted repeat regions. Phylogenetic analysis revealed that A. pilosa var. nepalensis and A. pilosa are closely related. Result of this study could provide genetic information for further research of A. pilosa var. nepalensis.

Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2.

There is increasing evidence that innate and adaptive immune responses are intimately linked. This linkage is in part mediated through the recognition of conserved microbial products by Toll-like receptors (TLRs). Detection of microbial products by TLRs can result in induction of inflammatory cytokines and activation of professional antigen-presenting cells, thereby enhancing adaptive immune responses. Here, we show that human beta-defensin-3 (hBD-3), an innate antimicrobial peptide, can induce expression of the costimulatory molecules CD80, CD86, and CD40, on monocytes and myeloid dendritic cells in a TLR-dependent manner. Activation of monocytes by hBD-3 is mediated by interaction with TLRs 1 and 2, resulting in signaling that requires myeloid differentiating factor 88 and results in IL-1 receptor-associated kinase-1 phosphorylation. In studies with HEK cells engineered to express various TLRs, we show that activation of NF-kappaB by hBD-3 depends on the expression of both TLR1 and TLR2. Thus, human TLR signaling is not restricted to recognition of microbial patterns but also can be initiated by host-derived peptides such as hBD-3.

Identification of second primary tumors from lung metastases in patients with esophageal squamous cell carcinoma using whole-exome sequencing.

Esophageal squamous cell carcinoma (ESCC) patients with a synchronous or metachronous lung tumor can be diagnosed with lung metastasis (LM) or a second primary tumor (SPT), but the accurate discrimination between LM and SPT remains a clinical dilemma. This study aimed to investigate the feasibility of using the whole-exome sequencing (WES) technique to distinguish SPT from LM. Methods: We performed WES on 40 tumors from 14 patients, including 12 patients with double squamous cell carcinomas (SCCs) of the esophagus and lung (lymph node metastases were sequenced as internal controls) diagnosed as LM according to pathological information and 2 patients with paired primary ESCC and non-lung metastases examined as external controls. Results: Shared genomic profiles between esophageal (T) and lung (D) tumors were observed in 7 patients, suggesting their clonal relatedness, thus indicating that the lung tumors of these patients should be LM. However, distinct genomic profiles between T and D tumors were observed in the other 5 patients, suggesting the possibility of SPTs that were likely formed through independent multifocal oncogenesis. Conclusions: Our data demonstrate the limitations and insufficiency of clinicopathological criteria and that WES could be useful in understanding the clonal relationships of multiple SCCs.

The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals.

Metabolic diseases are the most common and rapidly growing health issues worldwide. The massive population-based human genetics is crucial for the precise prevention and intervention of metabolic disorders. The China Metabolic Analytics Project (ChinaMAP) is based on cohort studies across diverse regions and ethnic groups with metabolic phenotypic data in China. Here, we describe the centralized analysis of the deep whole genome sequencing data and the genetic bases of metabolic traits in 10,588 individuals from the ChinaMAP. The frequency spectrum of variants, population structure, pathogenic variants and novel genomic characteristics were analyzed. The individual genetic evaluations of Mendelian diseases, nutrition and drug metabolism, and traits of blood glucose and BMI were integrated. Our study establishes a large-scale and deep resource for the genetics of East Asians and provides opportunities for novel genetic discoveries of metabolic characteristics and disorders.

Conceptual Perspectives: Bacterial Antimicrobial Peptide Induction as a Novel Strategy for Symbiosis with the Human Host.

Human beta defensins (hBDs) are small cationic peptides, expressed in mucosal epithelia and important agents of innate immunity, act as antimicrobial and chemotactic agents at mucosal barriers. In this perspective, we present evidence supporting a novel strategy by which the oral bacterium Fusobacterium nucleatum induces hBDs and other antimicrobial peptides (AMPs) in normal human oral epithelial cells (HOECs) and thereby protects them from other microbial pathogens. The findings stress (1) the physiological importance of hBDs, (2) that this strategy may be a mechanism that contributes to homeostasis and health in body sites constantly challenged with bacteria and (3) that novel properties identified in commensal bacteria could, one day, be harnessed as new probiotic strategies to combat colonization of opportunistic pathogens. With that in mind, we highlight and review the discovery and characterization of a novel lipo-protein, FAD-I (Fusobacterium Associated Defensin Inducer) associated with the outer membrane of F. nucleatum that may act as a homeostatic agent by activating endogenous AMPs to re-equilibrate a dysregulated microenvironment. FAD-I has the potential to reduce dysbiosis-driven diseases at a time when resistance to antibiotics is increasing. We therefore postulate that FAD-I may offer a new paradigm in immunoregulatory therapeutics to bolster host innate defense of vulnerable mucosae, while maintaining physiologically responsive states of inflammation.