Inferring Incidence of Unreported SARS-CoV-2 Infections Using Seroprevalence of Open Reading Frame 8 Antigen, Hong Kong.

We tested seroprevalence of open reading frame 8 antigens to infer the number of unrecognized SARS-CoV-2 Omicron infections in Hong Kong during 2022. We estimate 33.6% of the population was infected, 72.1% asymptomatically. Surveillance and control activities during large-scale outbreaks should account for potentially substantial undercounts.

Egg-adaptive mutations of human influenza H3N2 virus are contingent on natural evolution.

Egg-adaptive mutations in influenza hemagglutinin (HA) often emerge during the production of egg-based seasonal influenza vaccines, which contribute to the largest share in the global influenza vaccine market. While some egg-adaptive mutations have minimal impact on the HA antigenicity (e.g. G186V), others can alter it (e.g. L194P). Here, we show that the preference of egg-adaptive mutation in human H3N2 HA is strain-dependent. In particular, Thr160 and Asn190, which are found in many recent H3N2 strains, restrict the emergence of L194P but not G186V. Our results further suggest that natural amino acid variants at other HA residues also play a role in determining the preference of egg-adaptive mutation. Consistently, recent human H3N2 strains from different clades acquire different mutations during egg passaging. Overall, these results demonstrate that natural mutations in human H3N2 HA can influence the preference of egg-adaptation mutation, which has important implications in seed strain selection for egg-based influenza vaccine.

HLA-G-ILT2 interaction contributes to suppression of bone marrow B cell proliferation in acquired aplastic anemia.

Acquired aplastic anemia (AA) is an autoimmune disease characterized by hematopoietic stem and progenitor cell destruction in bone marrow. The non-classic human leukocyte class I antigen (HLA-) G interacts with multiple cell subsets, such as T cells and B cells. HLA-G exerts powerful immune suppression by binding with its receptors, immunoglobulin-like transcripts (ILTs). Here, we compared 46 AA patients and 28 healthy controls. Soluble HLA-G levels in bone marrow supernatants from AA patients were higher than controls. The proportion of bone marrow B cells was decreased and the ILT2-expressing cells among CD19+ cells were increased in AA patients. In addition, the percentage of mature B cells among marrow B cells was increased in AA patient, while the percentage of pro-B plus pre-B cells was decreased. More immature B cells and pro-B plus pre-B cells expressed ILT2 in AA patients than in controls, while mature B cells expressing ILT2 did not differ significantly. Functional studies demonstrated that high-level soluble HLA-G inhibited bone marrow B cell proliferation by interacting with ILT2 in AA, and was blocked by anti-HLA-G and anti-ILT2 monoclonal antibodies. Together, these results suggest that the abnormal decrease of pro-B plus pre-B cells in AA patients was related to the enhanced suppression by the excess HLA-G and ILT2 proteins. Therapeutic blockade of the HLA-G-ILT2 interaction may help to normalize bone marrow B cell proliferation.

Human leukocyte antigen-G upregulates immunoglobulin-like transcripts and corrects dysfunction of immune cells in immune thrombocytopenia.

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class I antigen with potent immune-inhibitory function. HLA-G benefit patients in allotransplantation and autoimmune diseases by interacting with its receptors, immunoglobulinlike transcripts. Here we observed significantly less HLA-G in plasma from immune thrombocytopenia (ITP) patients positive for anti-platelet autoantibodies compared with autoantibodies-negative patients or healthy controls, while we found that HLA-G is positively correlated with platelet counts in both patients and healthy controls. We also found less membranebound HLA-G and immunoglobulin-like transcripts on CD4+ and CD14+ cells in patients. Recombinant HLA-G upregulated immunoglobulin-like transcript 2 expression on CD4+ and immunoglobulin-like transcript 4 on CD14+ cells. HLA-G upregulated IL-4 and IL-10, and downregulated tumor necrosis factor-a, IL-12 and IL-17 secreted by patient peripheral blood mononuclear cells, suggesting a stimulation of Th2 differentiation and downregulation of Th1 and Th17 immune response. HLA-G-modulated dendritic cells from ITP patients showed decreased expression of CD80 and CD86, and suppressed CD4+ T-cell proliferation compared to unmodulated cells. Moreover, HLA-G-modulated cells from patients induced less platelet apoptosis. HLA-G administration also significantly alleviated thrombocytopenia in a murine model of ITP. In conclusion, our data demonstrated that impaired expression of HLA-G and immunoglobulin-like transcripts is involved in the pathogenesis of ITP; recombinant HLA-G can correct this abnormality via upregulation of immunoglobulin-like transcripts, indicating that HLA-G can be a diagnostic marker and a therapeutic option for ITP.

Efficacy and safety between early use and late use of celecoxib in hip osteoarthritis patients who receive total hip arthroplasty: a randomized, controlled study.

Celecoxib is commonly used for pain management after total hip arthroplasty (THA), while the optimal timing of analgesic celecoxib remains unclear. This randomized, controlled study aimed to investigate the pain control efficacy and safety of preoperative celecoxib versus postoperative celecoxib in osteoarthritis (OA) patients undergoing THA. Totally, 192 hip OA patients about to undergo THA were randomized into pre-treatment group (N = 96) and post-treatment group (N = 96). The former was given 400 mg celecoxib at 4 h before THA, 200 mg at 4 h after THA, and then 200 mg every 12 h until 72 h post-operation. The latter was given 400 mg celecoxib at 4 h after THA, and then 200 mg every 12 h until 72 h post-operation. Pain at rest visual analog scale (VAS) score at 6 h, and pain at flexion VAS scores at 6 h, 12 h, and on D1, D2 were decreased in pre-treatment group compared to post-treatment group (all P < 0.05). Furthermore, additional consumption of patient-controlled analgesia (PCA) (P = 0.006) and total consumption of PCA (P = 0.006) were both reduced in pre-treatment group compared to post-treatment group. Meanwhile, compared to post-treatment group, patient satisfaction in pre-treatment group was higher on D1 (P = 0.010) and D2 (P = 0.039). While, Harris hip score showed no difference between pre-treatment group and post-treatment group on M1 or M3 (both P > 0.05). In conclusion, preoperative celecoxib exhibits better analgesic efficacy and patients' satisfaction management with similar tolerance compared to postoperative celecoxib in hip OA patients undergoing THA.

Curcumin Suppresses IL-1ß Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome.

Turmeric is traditionally used as a spice and coloring in foods. Curcumin is the primary active ingredient in the turmeric, and compelling evidence has shown that it has the ability to inhibit inflammation. However, the mechanism mediating its anti-inflammatory effects are not fully understood. We report that curcumin inhibited caspase-1 activation and IL-1ß secretion through suppressing LPS priming and the inflammasome activation pathway in mouse bone marrow-derived macrophages. The inhibitory effect of curcumin on inflammasome activation was specific to the NLRP3, not to the NLRC4 or the AIM2 inflammasomes. Curcumin inhibited the NLRP3 inflammasome by preventing K+ efflux and disturbing the downstream events, including the efficient spatial arrangement of mitochondria, ASC oligomerization, and speckle formation. Reactive oxygen species, autophagy, sirtuin-2, or acetylated α-tubulin was ruled out as the mechanism by which curcumin inhibits the inflammasome. Importantly, in vivo data show that curcumin attenuated IL-1ß secretion and prevented high-fat diet-induced insulin resistance in wide-type C57BL/6 mice but not in Nlrp3-deficient mice. Curcumin also repressed monosodium urate crystal-induced peritoneal inflammation in vivo. Taken together, we identified curcumin as a common NLRP3 inflammasome activation inhibitor. Our findings reveal a mechanism through which curcumin represses inflammation and suggest the potential clinical use of curcumin in NLRP3-driven diseases.

High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia.

Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature cells and natural inhibitors of adaptive immunity. In this study, the MDSC population was evaluated in adult patients with primary immune thrombocytopenia (ITP), where cell-mediated immune mechanisms are involved in platelet destruction. Our data demonstrated that both the numbers and suppressive functions of MDSCs were impaired in the peripheral blood and spleens of patients with ITP compared with healthy control patients. High-dose dexamethasone (HD-DXM) treatment rescued MDSC numbers in patients with ITP. And DXM modulation promoted the suppressive function of MDSCs induced in vitro. Moreover, the expression of interleukin 10 and transforming growth factor ß was significantly upregulated in DXM-modulated MDSCs compared with the unmodulated cultures. DXM-modulated MDSCs inhibited autologous CD4(+)T-cell proliferation and significantly attenuated cytotoxic T lymphocyte-mediated platelet lysis, further indicating enhanced control over T-cell responses. Elevated expression of the transcription factor Ets1 was identified in DXM-modulated MDSCs. Transfection of Ets-1 small interfering RNA efficiently blocked regulatory effects of MDSCs, which almost offset the augmentation of MDSC function by DXM. Meanwhile, splenocytes from CD61 knockout mice immunized with CD61(+)platelets were transferred into severe combined immunodeficient (SCID) mouse recipients (C57/B6 background) to induce a murine model of severe ITP. We passively transferred the DXM-modulated MDSCs induced from bone marrow of wild-type C57/B6 mice into the SCID mouse recipients, which significantly increased platelet counts in vivo compared with those receiving splenocyte engraftment alone. These findings suggested that impaired MDSCs are involved in the pathogenesis of ITP, and that HD-DXM corrected MDSC functions via a mechanism underlying glucocorticoid action and Ets1.

siRNA targeting TCTP suppresses osteosarcoma cell growth and induces apoptosis in vitro and in vivo.

Osteosarcoma (OS) remains the most frequent primary malignant bone tumor in adolescents. However, the molecular cause of the disease is poorly elucidated. In the present study, we primarily found that translationally controlled tumor protein (TCTP) was overexpressed in human OS tissues and cell lines. To investigate the function of TCTP in OS cell growth, an RNA interference lentivirus system was employed to deplete TCTP expression in Saos-2 and U2OS cell lines. Specific knockdown of TCTP significantly impaired cell proliferation and colony-formation capacity in both OS cell lines. Moreover, depletion of TCTP caused a significant accumulation of OS cells in the S phase and eventually induced cell apoptosis. Expression levels of the G2/M phase regulators cyclin B1 and Cdc25A were decreased, and apoptotic markers Bad and caspase-3 were increased in both OS cell lines after depletion of TCTP. Furthermore, depletion of TCTP potently inhibited the growth of xenografts in nude mice. Our results indicate that inhibition of TCTP expression exerts potential antitumor activity and may be a novel therapeutic approach in human OS.

Inhibition of EGFR-induced glucose metabolism sensitizes chondrosarcoma cells to cisplatin.

Chondrosarcomas are malignant cartilage-forming tumors which are resistant to conventional chemotherapy and radiotherapy. By searching in Oncomine which is a cancer microarray database and web-based data mining platform, we found Glut1 and LDHA were upregulated in human chondrosarcoma patient samples. In this study, we reported total epidermal growth factor receptor (EGFR) expression and phosphorylated EGFR were highly activated in human chondrosarcoma cell lines. In addition, overexpression of EGFR contributed to cisplatin resistance. EGFR promoted glucose metabolism of chondrosarcoma cells through the upregulation of glycolysis key enzymes. Interestingly, cisplatin-resistant chondrosarcoma cells showed upregulated glucose metabolism and EGFR signaling pathway. Finally, we demonstrated that the combination of either EGFR inhibitor or anaerobic glycolysis inhibitor with cisplatin showed synergistically inhibitory effects on cisplatin-resistant chondrosarcoma cells through the inducements of apoptosis and cell cycle arrest. Our project proposed a novel function of EGFR in the regulation of glucose metabolism in chondrosarcoma cells and contributed to the development of therapeutic strategies for the clinical treatment of chondrosarcoma patient.

Elevated Th22 cells correlated with Th17 cells in peripheral blood of patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematological tumor in which progress T helper (Th) subsets including Th22, Th17, and Th1 cells play a pivotal role. However, the role of T helper (Th) subsets in the immune pathogenesis of AML remains unclear. Here, we investigated frequencies of Th22, Th17, pure Th17, and Th1 cells in the peripheral blood (PB) of AML patients. We demonstrated that Th22, Th17, and pure Th17 in newly-diagnosed (ND) and non-complete remission (Non-CR) AML patients and plasma IL-22 in ND AML patients were significantly increased. Retinoid-related orphan receptor C (RORC) expression was significantly elevated in CR and Non-CR AML patients. However, Th1 in ND AML patients and IL-17 in ND, Non-CR or CR AML patients was significantly decreased compared with controls. Moreover, Th22 and IL-22 showed positive correlation with pure Th17, but Th22 showed negative correlation with Th1 in ND AML patients. RORC showed positive correlation with Th22 and approximately positive correlation with pure Th17 in Non-CR patients. PB blast cell showed positive correlation with Th22 and negative correlation with Th1 in ND AML patients. Our results indicate that Th22 and pure Th17 cells conjointly contribute to the pathogenesis of AML and might be promising novel clinical index for AML.

[Research on rapid and quantitative detection method for organophosphorus pesticide residue].

The methods of physical-chemical inspection is adopted in the traditional pesticide residue detection, which require a lot of pretreatment processes, are time-consuming and complicated. In the present study, the authors take chlorpyrifos applied widely in the present agricultural field as the research object and propose a rapid and quantitative detection method for organophosphorus pesticide residues. At first, according to the chemical characteristics of chlorpyrifos and comprehensive chromogenic effect of several colorimetric reagents and secondary pollution, the pretreatment of the scheme of chromogenic reaction of chlorpyrifos with resorcin in a weak alkaline environment was determined. Secondly, by analyzing Uv-Vis spectrum data of chlorpyrifos samples whose content were between 0. 5 and 400 mg kg-1, it was confirmed that the characteristic information after the color reaction mainly was concentrated among 360 approximately 400 nm. Thirdly, the full spectrum forecasting model was established based on the partial least squares, whose correlation coefficient of calibration was 0. 999 6, correlation coefficient of prediction reached 0. 995 6, standard deviation of calibration (RMSEC) was 2. 814 7 mg kg-1, and standard deviation of verification (RMSEP) was 8. 012 4 mg kg-1. Fourthly, the wavelengths whose center wavelength is 400 nm was extracted as characteristic region to build a forecasting model, whose correlation coefficient of calibration was 0. 999 6, correlation coefficient of prediction reached 0. 999 3, standard deviation of calibration (RMSEC) was 2. 566 7 mg kg-1 , standard deviation of verification (RMSEP) was 4. 886 6 mg kg-1, respectively. At last, by analyzing the near infrared spectrum data of chlorpyrifos samples with contents between 0. 5 and 16 mg kg-1, the authors found that although the characteristics of the chromogenic functional group are not obvious, the change of absorption peaks of resorcin itself in the neighborhood of 5 200 cm-' happens. The above-mentioned experimental results show that the proposed method is effective and feasible for rapid and quantitative detection prediction for organophosphorus pesticide residues. In the method, the information in full spectrum especially UV-Vis spectrum is strengthened by chromogenic reaction of a colorimetric reagent, which provides a new way of rapid detection of pesticide residues for agricultural products in the future.

Persimmon leaf polyphenols as potential ingredients for modulating starch digestibility: Effect of starch-polyphenol interaction.

The interaction mode between persimmon leaf polyphenols (PLP) and corn starch with different amylose content and its effect on starch digestibility was studied. Results of iodine binding test, TGA, and DSC revealed that PLP interacted with starch and reduced the iodine binding capacity and thermal stability of starch. High amylopectin corn starch (HAPS) interacted with PLP mainly via hydrogen bonds, since the FT-IR of HAPS-PLP complex showed higher intensity at 3400 cm-1 and an obvious shift of 21 cm-1 to shorter wavelength, and the chemical shifts of protons in 1H NMR and the shift of C-6 peak in 13C NMR of HAPS moved to low field with the addition of PLP. Results of 1H NMR also showed the preferential formation of hydrogen bonds between PLP and OH-3 of HAPS. Different from HAPS, PLP formed V-type inclusion complex with high amylose corn starch (HAS) because XRD of HAS-PLP complex showed characteristic feature peaks of V-type inclusion complex and C-1 signal in 13C NMR of PLP-complexed HAS shifted to low field. Interaction with PLP reduced starch digestibility and HAS-PLP complex resulted in more resistant starch production than HAPS-PLP complex. To complex PLP with starch might be a potential way to prepare functional starch with slower digestion.

Epistasis mediates the evolution of the receptor binding mode in recent human H3N2 hemagglutinin.

The receptor-binding site of influenza A virus hemagglutinin partially overlaps with major antigenic sites and constantly evolves. In this study, we observe that mutations G186D and D190N in the hemagglutinin receptor-binding site have coevolved in two recent human H3N2 clades. X-ray crystallography results show that these mutations coordinately drive the evolution of the hemagglutinin receptor binding mode. Epistasis between G186D and D190N is further demonstrated by glycan binding and thermostability analyses. Immunization and neutralization experiments using mouse and human samples indicate that the evolution of receptor binding mode is accompanied by a change in antigenicity. Besides, combinatorial mutagenesis reveals that G186D and D190N, along with other natural mutations in recent H3N2 strains, alter the compatibility with a common egg-adaptive mutation in seasonal influenza vaccines. Overall, our findings elucidate the role of epistasis in shaping the recent evolution of human H3N2 hemagglutinin and substantiate the high evolvability of its receptor-binding mode.

Triple-function chitosan-based film for pork and shrimp packaging.

A film simultaneously with colorimetric, fluorescent and active functions was engineered using chitosan (CS) and polyvinyl alcohol (PVA) as the film matrix and curcumin-ß-cyclodextrin complex (Cur-ß-CD) as the indicator for freshness monitoring and maintaining of pork and shrimp. In addition to the efficacy of prolonging shelf life, the film's color could change from yellow to orange with ΔE > 5 and its fluorescence intensity could decrease during storage. The incorporation of PVA significantly enhanced the mechanical properties of CS film with tensile strength of 31.80 MPa and elongation at break of 127.22 %. The Cur-ß-CD improved the antioxidant and antibacterial properties, water contact angle (from 86.3° to 111.2°), water vapor permeability (from 3.28 × 10-10 g (m s Pa)-1 to 0.42 × 10-10 g (m s Pa)-1) and mechanical properties of CS/PVA film. These results show the potential of the film as promising alternatives for intelligent and active food packaging.

Lack of neutralizing antibodies against influenza A viruses in adults during the 2022/2023 winter season - a serological study using retrospective samples collected in Hong Kong.

OBJECTIVES: Since the onset of the COVID-19 pandemic in 2020, there has been a significant decline in seasonal influenza infection cases in Hong Kong. However, this decline has also resulted in reduced opportunities for the development of influenza-specific antibodies in the community. The levels of antibodies required for protection against recently circulating influenza A viruses in the post-COVID-19 era remain unclear. METHODS: This study involved the analysis of paired plasma samples collected from 479 healthy adults in Hong Kong in 2021 and 2022. The neutralizing titers of plasma against influenza A (H1N1) and (H3N2) viruses circulating before and after the COVID-19 outbreak were determined using a microneutralization assay. RESULTS: The H1N1 and H3N2 vaccine strains selected for the 2022/23 season were found to be closely related to the recently circulating viruses. However, in the samples collected in 2022, only 14.61% and 0.42% showed a neutralization titer (MN50) ≥1:20 against H1N1 A/Wisconsin/588/2019 (H1/Wis19) and H3N2 A/Darwin/6/2021 (H3/Dar21), respectively. Notably, participants who reported receiving annual flu vaccinations exhibited a higher seropositive rate for H1/Wis19 compared to those who had never received the flu vaccine (28.06% vs. 5.30%). CONCLUSION: Our results indicate that adults in Hong Kong generally lack neutralizing antibodies against circulating influenza A viruses, particularly H3N2. These findings underscore the importance of promoting flu vaccination in the post-COVID-19 era.

Omicron BA.1-specific T-cell responses in adults vaccinated with CoronaVac or BNT162b2 in Hong Kong: an observational cohort study.

BACKGROUND: The primary aim of using vaccines in public health responses to SARS-CoV-2 variants of concern is to reduce incidence of severe disease, for which T-cell responses are essential. There is a paucity of data on vaccine-induced T-cell immunity to omicron (B.1.1.529). We aimed to compare SARS-CoV-2 omicron BA.1-specific T-cell responses in adults vaccinated with CoronaVac or BNT162b2. METHODS: For this observational cohort, we recruited adults (aged ≥18 years) from three vaccination centres in Hong Kong. We included participants from four cohorts (cohort 1: participants who received two doses of either BNT162b2 or CoronaVac, cohort 2: participants who received two doses and a booster, cohort 3: participants who received two doses and a booster and had a breakthrough omicron infection, and cohort 4: participants who had a previous non-omicron infection and subsequently received one dose of vaccine). People with confirmed history of COVID-19 at recruitment were excluded from cohort 1 and cohort 2. We collected blood samples before vaccination (for cohort 1 and 2), 1-month following vaccination (for all cohorts), and during convalescence for cohort 3 and 4) and determined the proportion of IFNγ+CD4+ and IFNγ+CD8+ T cells in peripheral blood against SARS-CoV-2 using flow cytometry with peptide pools of SARS-CoV-2 wild type or omicron BA.1. The primary outcome was proportion of CD4+ and CD8+ T cells against SARS-CoV-2 1 month after exposure (ie, vaccination or breakthrough infection). FINDINGS: Overall, between May 21, 2020, and Aug 31, 2021, we recruited 659 participants (231 [35%] men and 428 [65%] women). Of these participants, 428 were included in cohort 1 (214 [50%] received BNT162b2 and 214 [50%] received CoronaVac); 127 in cohort 2 (48 [38%] received all BNT162b2, 40 [31%] received all CoronaVac, and 39 [31%] received two CoronaVac and a booster with BNT162b2); 58 in cohort 3, and 46 in cohort 4 (16 [35%] received CoronaVac and 30 [65%] received BNT162b2). Vaccine-induced T-cell responses to the wild-type and omicron BA.1 variants were generally similar in adults receiving two doses of either CoronaVac (CD4+ cells p=0·33; CD8+ cells p=0·70) or BNT162b2 (CD4+ cells p=0·28; CD8+ cells p=1·0). Using a peptide pool of all structural proteins for stimulation, BNT162b2 induced a higher median frequency of omicron-specific CD4+ T cells in adults younger than 60 years (CD4+ cells 0·012% vs 0·010%, p=0·031; CD8+ cells 0·003% vs 0·000%, p=0·055) and omicron-specific CD8+ T cells in people aged 60 years or older (CD4+ cells 0·015% vs 0·006%, p=0·0070; CD8+ cells 0·007% vs 0·000%, p=0·035). A booster dose of either BNT162b2 or CoronaVac after two doses of CoronaVac boosted waning T-cell responses, but T-cell responses did not exceed those at 1 month after the second dose (CoronaVac CD4+ p=0·41, CD8+ p=0·79; BNT162b2 CD4+ p=0·70 CD8+ p=0·80). INTERPRETATION: The evidence that mRNA and inactivated vaccines based on the ancestral SARS-CoV-2 virus elicited T-cell responses to SARS-CoV-2 omicron variants might explain the high observed vaccine effectiveness against severe COVID-19 shown by both types of vaccine, despite great differences in neutralising antibody responses. The use of either vaccine can be considered if the primary aim is to reduce severity and death caused by the new omicron subvariants; however, BNT162b2 is preferable for adults older than 60 years. FUNDING: The Health and Medical Research Fund Commissioned Research on the Novel Coronavirus Disease and S H Ho Foundation.

Age-related seroprevalence trajectories of seasonal coronaviruses in children including neonates in Guangzhou, China.

OBJECTIVES: Four seasonal coronaviruses, including human coronavirus (HCoV)-229E and HCoV-OC43, HCoV-NL63, and HCoV-HKU1 cause approximately 15-30% of common colds in adults. However, the full landscape of the immune trajectory to these viruses that covers the whole childhood period is still not well understood. METHODS: We evaluated the serological responses against the four seasonal coronaviruses in 1886 children aged under 18 years by using enzyme-linked immunosorbent assay. The optical density values against each HCoV were determined from each sample. Generalized additive models were constructed to determine the relationship between age and seroprevalence throughout the whole childhood period. The specific antibody levels against the four seasonal coronaviruses were also tested from the plasma samples of 485 pairs of postpartum women and their newborn babies. RESULTS: The immunoglobulin (Ig) G levels of the four seasonal coronaviruses in the mother and the newborn babies were highly correlated (229E: r = 0.63; OC43: r = 0.65; NL63: r = 0.69; HKU1: r = 0.63). The seroprevalences in children showed a similar trajectory in that the levels of IgG in the neonates dropped significantly and reached the lowest level after the age of around 1 year (229E: 1.18 years; OC43: 0.97 years; NL63: 1.01 years; HKU1: 1.02 years) and then resurgence in the children who aged older than 1 year. Using the lowest level from the generalized additive models as our cutoff, the seroprevalences for HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 were 98.11%, 96.23%, 96.23% and 94.34% at the age of 16-18 years. CONCLUSION: Mothers share HCoV-specific IgGs with their newborn babies and the level of maternal IgGs waned at around 1 year after birth. The resurgence of the HCoV-specific IgGs was found thereafter with the increase in age suggesting repeated infection occurred in children.

Orexin A prevents degradation of the articular matrixes in human primary chondrocyte culture.

Excessive production of pro-inflammatory cytokines such as interleukin-1ß (IL-1ß) plays a key role in the pathophysiological development of osteoarthritis (OA). Orexin A is an important peptide of hypothalamic origin, which has displayed its multiple biological functions in several chronic diseases via activation of its specific G-protein coupled receptors, orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R). In this study, we aimed to characterize the protective effects of orexin A against IL-1ß-induced degradation of articular cartilage matrixes in human chondrocytes. Our results indicate that OX1R but not OX2R was expressed in human chondrocytes. We also found that the expression of OX1R was significantly lower in chondrocytes from OA patients, and that treatment with IL-1ß decreased the expression of OX1R in a dose-dependent manner. The presence of orexin A ameliorated IL-1ß-induced degradation of type II collagen and aggrecan, the two major components of articular cartilage matrixes. Our results also show that orexin A prevented IL-1ß-induced expression of catabolic enzymes such as MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5. Mechanistically, orexin A treatment abolished activation of the transcriptional factor NF-κB via inhibition of KKα/IκB-α phosphorylation and IκB-α degradation. These findings suggest that orexin A might act as an effective therapeutic agent for the treatment of OA.

Pre-transplantation thymic function is associated with the risk of acute graft versus host disease and cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation.

OBJECTIVES: To analyze the kinetics of T-cell subsets and thymic function reconstitution after allogeneic hematopoietic stem cell transplantation (AHSCT); to determine whether sjTREC (signal joint TCR rearrangement excision circle) and CD31-positive recent thymic emigrant (CD31 + RTE) are correlated with acute graft versus host disease (aGVHD) or CMV (cytomegalovirus) viremia after AHSCT. METHODS: Forty-nine patients who underwent AHSCT in our institution were prospectively enrolled. Periphery blood samples were collected before conditioning and at 1, 2, 3 months after AHSCT. T-cell subsets were analyzed with flow cytometry. Genomic DNA was purified from peripheral blood mononuclear cells (PBMCs), and sjTREC was quantified by real-time PCR. Impact of sjTREC and CD31 + RTE on aGVHD and CMV viremia was evaluated by univariate and multivariate Cox regression analyses. RESULTS: The analyzed T-cell subsets and sjTREC of patients before AHSCT were all significantly lower than those of healthy donors (p < 0.05). sjTREC and CD31 + RTE were remarkably decreased in 3 months after AHSCT (p < 0.05). Patients with lower pre-transplantation sjTREC and CD31 + RTE level had higher incidence of CMV viremia after AHSCT (p < 0.05). sjTREC/106 PBMCs was negatively correlated with aGVHD (p = 0.024). CONCLUSION: Thymic function was impaired before transplantation, and was consistently decreased in 3 months after AHSCT. Patients who had lower pre-transplantation sjTREC level were at high risk of aGVHD and CMV viremia after AHSCT, low pre-transplantation CD31 + RTE was correlated with CMV viremia after AHSCT.