KMCP: accurate metagenomic profiling of both prokaryotic and viral populations by pseudo-mapping.

MOTIVATION: The growing number of microbial reference genomes enables the improvement of metagenomic profiling accuracy but also imposes greater requirements on the indexing efficiency, database size and runtime of taxonomic profilers. Additionally, most profilers focus mainly on bacterial, archaeal and fungal populations, while less attention is paid to viral communities. RESULTS: We present KMCP (K-mer-based Metagenomic Classification and Profiling), a novel k-mer-based metagenomic profiling tool that utilizes genome coverage information by splitting the reference genomes into chunks and stores k-mers in a modified and optimized Compact Bit-Sliced Signature Index for fast alignment-free sequence searching. KMCP combines k-mer similarity and genome coverage information to reduce the false positive rate of k-mer-based taxonomic classification and profiling methods. Benchmarking results based on simulated and real data demonstrate that KMCP, despite a longer running time than all other methods, not only allows the accurate taxonomic profiling of prokaryotic and viral populations but also provides more confident pathogen detection in clinical samples of low depth. AVAILABILITY AND IMPLEMENTATION: The software is open-source under the MIT license and available at https://github.com/shenwei356/kmcp. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Clinical characteristics and immunogenicity after Omicron breakthrough infection in patients with chronic hepatitis B infection: A longitudinal observational study.

The clinical and immunological features after breakthrough infection (BTI) during Omicron wave in patients with chronic hepatitis B virus infection (CHB) are still unclear. A total of 101 patients with CHB from our previous coronavirus disease 2019 (COVID-19) vaccination cohort (NCT05007665), were continued to be followed up at the Second Affiliated Hospital of Chongqing Medical University after BTI, while an additional 39 healthcare workers after BTI were recruited as healthy controls (HCs). Clinical data were collected using questionnaire survey and electronic medical record. Blood samples were used to determine the antibody responses, as well as B and T cell responses. After BTI, the clinical symptoms of COVID-19 were mild to moderate in patients with CHB, with a median duration of 5 days. Compared with HCs, patients with CHB were more susceptible to develop moderate COVID-19. The liver function was not significantly damaged, and HBV-DNA was not activated in patients with CHB after BTI. Patients with CHB could elicit robust antibody responses after BTI (NAbs 13.0-fold, BA.5 IgG: 24.2-fold, respectively), which was also significantly higher than that in every period after vaccination (all p < 0.001), and compared to that in HCs after BTI. The CD4+, cTfh, and CD8+ T cell responses were also augmented in patients with CHB after BTI, while exhibiting comparability to those observed in HCs. In patients with CHB after BTI, the immune imprint was observed in B cell responses, rather than in T cell responses. In conclusion, Omicron breakthrough infection induced mild to moderate COVID-19 symptoms in patients with CHB, without exacerbating the progress of liver diseases. Meanwhile, BTI demonstrated the ability to induce robust antibody and T cell responses in patients with CHB, which was comparable to those observed in HCs.

A potential antiviral role for CCR5+CD8+ T cells in children with hepatitis B.

While dysfunctional exhausted CD8+ T cells hamper viral control when children acquire hepatitis B virus (HBV) infection, it's crucial to recognize that CD8+ T cells have diverse phenotypes and functions. This study explored a subset of CD8+ T cells expressing C-C chemokine receptor type 5 (CCR5) in children with HBV infection. Thirty-six patients in the immune tolerant group, 33 patients in the immune active group, 55 patients in the combined response group, and 22 healthy control children were enrolled. The frequency, functional molecules, and effector functions of the CCR5+CD8+ T cell population in different groups were evaluated. The frequency of CCR5+CD8+ T cells correlated positively with the frequency of CCR5+CD4+ T cells and patient age, and it correlated negatively with alanine aminotransferase, aspartate transaminase, HBV DNA, hepatitis B surface antigen, and lactic dehydrogenase levels. CCR5+CD8+ T cells had higher levels of inhibitory and activated receptors and produced higher levels of IFN-γ, IL-2, and TNF-α than CCR5-CD8+ T cells. CCR5+CD8+ T cells were partially exhausted but possessed a stronger antiviral activity than CCR5-CD8+ T cells. The identification of this subset increases our understanding of CD8+ T cell functions and serves as a potential immunotherapeutic target for children with HBV infection.

Clinical and immunological features of COVID-19 in patients with anti-MDA5 dermatomyositis during the omicron wave in Chongqing, China.

Patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5) dermatomyositis (DM) have a higher risk of coronavirus disease 2019 (COVID-19) infection. In this longitudinal observational study, we aimed to investigate the clinical and immunological features of these patients after COVID-19 infection. A total of 73 patients with anti-MDA5 DM were recruited from the Second Affiliated Hospital of Chongqing Medical University during the Omicron wave epidemic. Clinical data were collected by questionnaire survey and electronic medical records. Blood samples were used to determine the immunity responses. From December 9, 2022 to March 31, 2023, 67 patients were eligible for final analysis; 68.7% of them were infected with COVID-19. The most common symptoms observed in COVID-19 were upper respiratory symptoms, most cases were mild or moderate (97.8%). The clinical laboratory indexes were relativity stable in patients after infection (all p > 0.05). Vaccination is not a protective factor against the Omicron infection (odds ratio: 2.69, 95% confidence interval: 0.81-8.93, p = 0.105). Both wildtype (WT) neutralizing antibodies titer and BA.5-specific immunoglobulin G titer were significantly enhanced after infection (all p < 0.01), which was as high as healthy controls (HCs). The memory B-cell responses were similar between the patients with anti-MDA5 DM and HCs (p > 0.05). However, both the WT-specific CD8+ T cells and CD4+ T cells were reduced in patients with anti-MDA5 DM (all p < 0.05). In conclusion, patients with anti-MDA5 DM did not deteriorate the COVID-19, in turn, COVID-19 infection did not increase the risk of anti-MDA5 DM exacerbation. The humoral responses were robust but the cellular responses were weakened after COVID-19 infection.

Risk of waning humoral responses after inactivated or subunit recombinant SARS-CoV-2 vaccination in patients with chronic diseases: Findings from a prospective observational study in China.

Heterogeneity of antibody responses has been reported in SARS-CoV-2 vaccination recipients with underlying diseases. We investigated the impact of the presence of comorbidities on the humoral response to SARS-CoV-2 vaccination in patients with chronic disease (PWCD) and assessed the effect of the number of comorbidities on the humoral response to vaccination. In this study, neutralizing antibodies (NAbs) and IgG antibodies against the receptor-binding domain (RBD-IgG) were monitored following a full-course vaccination. In total, 1400 PWCD (82.7%, inactivated vaccines; 17.3%, subunit recombinant vaccine) and 245 healthy controls (65.7% inactivated vaccines, 34.3% subunit recombinant vaccine) vaccinated with inactivated or subunit recombinant SARS-CoV-2 vaccines, were included. The seroconversion and antibody levels of the NAbs and RBD-IgG were different in the PWCD group compared with those in the control group. Chronic hepatitis B (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.46-0.93), cancer (OR: 0.65; 95% CI: 0.42-0.99), and diabetes (OR: 0.50; 95% CI: 0.28-0.89) were associated with lower seroconversion of NAbs. Chronic kidney disease (OR: 0.29; 95% CI: 0.11-0.76), cancer (OR: 0.38; 95% CI: 0.23-0.62), and diabetes (OR: 0.37; 95% CI: 0.20-0.69) were associated with lower seroconversion of RBD-IgG. Only the presence of autoimmune disease showed significantly lower NAbs and RBD-IgG titers. Patients with most types of chronic diseases showed similar responses to the controls, but humoral responses were still significantly associated with the presence of ≥2 coexisting diseases. Our study suggested that humoral responses following SARS-CoV-2 vaccination are impaired in patients with certain chronic diseases.

Dynamic immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in people living with HIV: A longitudinal observational study.

People living with HIV (PLWH) have poor outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); vaccination reduces the associated mortality. The humoral immune response dynamics after booster inactivated vaccinations in PLWH remain unclear. In this longitudinal observational study, 100 PLWH after primary inactivated SARS-CoV-2 vaccination were consecutively recruited and followed up. After booster vaccination (BV), neutralizing antibodies (NAbs) were detected at 1 month from all the PLWH, and the titer increased sixfold compared to that associated with the primary vaccination (PV), similar to that in healthy controls after BV. The NAbs titer declined over time after BV, but remained higher at 6 months than after PV. The NAbs response was elevated after BV with CD4 count <200 cells/µL, it was the poorest among the different CD4 cell count subgroups. Similar results were observed for anti-RBD-IgG responses. Moreover, RBD-specific MBCs were significantly elevated after BV in PLWH. No serious AEs were observed after BV in PLWH. In conclusion, booster inactivated SARS-CoV-2 vaccination is well tolerated and can elicit robust and durable humoral responses in PLWH. PLWH may benefit from a third dose of the inactivated vaccine.

Humoral responses after primary and booster SARS-CoV-2 inactivated vaccination in patients with chronic hepatitis B virus infection: A longitudinal observational study.

Given the pandemic of severe acute respiratory syndrome coronavirus 2 Omicron variants, booster vaccination (BV) using inactivated virus vaccines (the third dose) has been implemented in China. However, the immune responses after BV, especially those against Omicron, in patients with chronic hepatitis B virus (HBV) infection (CHB) are unclear. In this prospective longitudinal study, 114 patients with CHB and 68 healthy controls (HCs) were recruited after receiving inactivated vaccination. The anti-receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibodies (NAbs), neutralization against Omicron (BA2.12.1, BA.4/5), and specific B/T cells were evaluated. In patients, anti-RBD IgG was elevated significantly after BV; the titers were as high as those in HCs. Similar results were obtained for the NAbs. However, compared with that against wild type (WT), the neutralization against Omicron was compromised after BV. The frequency of RBD+ atypical memory B cells increased, but spike-specific cluster of differentiation 4+ /8+ T cells remained unchanged after BV. Moreover, no serious adverse events or HBV reactivation were observed after BV. These results suggest that BV significantly enhanced antibody responses against WT; however, it resulted in compromised antibody responses against Omicron in patients with CHB. Hence, new all-in-one vaccines and optimal vaccination strategies should be studied promptly.

Impaired antibody responses were observed in patients with type 2 diabetes mellitus after receiving the inactivated COVID-19 vaccines.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have been reported to be more susceptible to 2019 novel coronavirus (2019-nCoV) and more likely to develop severe pneumonia. However, the safety and immunological responses of T2DM patients after receiving the inactivated vaccines are not quite definite. Therefore, we aimed to explore the safety, antibody responses, and B-cell immunity of T2DM patients who were vaccinated with inactivated coronavirus disease 2019 (COVID-19) vaccines. METHODS: Eighty-nine patients with T2DM and 100 healthy controls (HCs) were enrolled, all of whom had received two doses of full-course inactivated vaccines. At 21-105 days after full-course vaccines: first, the safety of the vaccines was assessed by questionnaires; second, the titers of anti-receptor binding domain IgG (anti-RBD-IgG) and neutralizing antibodies (NAbs) were measured; third, we detected the frequency of RBD-specific memory B cells (RBD-specific MBCs) to explore the cellular immunity of T2DM patients. RESULTS: The overall incidence of adverse events was similar between T2DM patients and HCs, and no serious adverse events were recorded in either group. Compared with HCs, significantly lower titers of anti-RBD-IgG (p = 0.004) and NAbs (p = 0.013) were observed in T2DM patients. Moreover, the frequency of RBD-specific MBCs was lower in T2DM patients than in HCs (p = 0.027). Among the 89 T2DM patients, individuals with lower body mass index (BMI) had higher antibody titers (anti-RBD-IgG: p = 0.009; NAbs: p = 0.084). Furthermore, we found that sex, BMI, and days after vaccination were correlated with antibody titers. CONCLUSIONS: Inactivated COVID-19 vaccines were safe in patients with T2DM, but the antibody responses and memory B-cell responses were significantly decreased compared to HCs. TRIAL REGISTRATION NUMBER AND DATE: NCT05043246. September 14, 2021. (Clinical Trials.gov).

Safety and antibody response to inactivated COVID-19 vaccine in patients with chronic hepatitis B virus infection.

BACKGROUND AND AIMS: The safety and antibody responses of coronavirus disease 2019 (COVID-19) vaccination in patients with chronic hepatitis B (CHB) virus infection is still unclear, and exploration in safety and antibody responses of COVID-19 vaccination in CHB patients is significant in clinical practice. METHODS: 362 adult CHB patients and 87 healthy controls at an interval of at least 21 days after a full-course vaccination (21-105 days) were enrolled. Adverse events (AEs) were collected by questionnaire. The antibody profiles at 1, 2 and 3 months were elucidated by determination of anti-spike IgG, anti-receptor-binding domain (RBD) IgG, and RBD-angiotensin-converting enzyme 2 blocking antibody. SARS-CoV-2 specific B cells were also analysed. RESULTS: All AEs were mild and self-limiting, and the incidence was similar between CHB patients and controls. Seropositivity rates of three antibodies were similar between CHB patients and healthy controls at 1, 2 and 3 months, but CHB patients had lower titers of three antibodies at 1 month. Compared to healthy controls, HBeAg-positive CHB patients had higher titers of three antibodies at 3 months (all P < .05) and a slower decline in antibody titers. Frequency of RBD-specific B cells was positively correlated with titers of anti-RBD IgG (OR = 1.067, P = .004), while liver cirrhosis, antiviral treatment, levels of HBV DNA, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total bilirubin (TB) were not correlated with titers of anti-RBD IgG. CONCLUSIONS: Inactivated COVID-19 vaccines were well tolerated, and induced effective antibody response against SARS-CoV-2 in CHB patients.

Urine α-fetoprotein and orosomucoid 1 as biomarkers of hepatitis B virus-associated hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth common malignant tumor worldwide, but current efficient and convenient screening methods remain lacking. This study aimed to discover a diagnostic or a screening biomarker from the urine of hepatitis B virus (HBV)-related HCC patients. We used iTRAQ coupled with mass spectrometry to identify candidate urinary proteins in a discovery cohort (n = 40). The selected proteins were confirmed using ELISA in a validation cohort (n = 140). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic (ROC) and qualitative diagnostic analysis. A total of 96 differentially expressed proteins were identified. Urinary α-fetoprotein (u-AFP) and orosomucoid 1 (u-ORM1) were selected as target proteins by bioinformatics analysis and were significantly higher in HCC than in non-HCC patients, as validated by Western blot analysis and ELISA. u-AFP had a strong correlation with serum AFP-L3 (Pearson's r = 0.944, P < 0.0001), indicating that u-AFP may be derived from circulating blood. The area under the curve (AUC) of u-AFP was 0.795 with a sensitivity of 62.5% and a specificity of 95.4%, which showed no significantly difference with serum AFP (se-AFP). The AUC was 0.864 as u-AFP and u-ORM1 were combined, and they performed much better than u-AFP or u-ORM1 alone. Qualitative diagnostic analysis showed that the positive predictive value of u-AFP was 90.1% and the diagnostic sensitivity of parallel combination of u-AFP and u-ORM1 was 85.1%. Taken together, AFP and ORM1 in the urine may be used as a diagnostic or screening biomarker of HCC, and studies on large samples are needed to validate the result.NEW & NOTEWORTHY This study provides a novel way to find biomarkers of hepatocellular carcinoma (HCC) and a new perspective of α-fetoprotein clinical application. The urine reagent strips may be helpful in high epidemic areas of HCC and in low-resource settings.

Ultrasonication-Triggered Ubiquitous Assembly of Magnetic Janus Amphiphilic Nanoparticles in Cancer Theranostic Applications.

The ultrasonication-triggered interfacial assembly approach was developed to synthesize magnetic Janus amphiphilic nanoparticles (MJANPs) for cancer theranostic applications, where the biocompatible octadecylamine is used as a molecular linker to mediate the interactions between hydrophobic and hydrophilic nanoparticles across the oil-water interface. The obtained Co cluster-embedded Fe3O4 nanoparticles-graphene oxide (CCIO-GO) MJANPs exhibited superior magnetic heating efficiency and transverse relaxivity, 64 and 4 times higher than that of commercial superparamagnetic iron oxides, respectively. The methodology has been applicable to nanoparticles of various dimensions (5-100 nm), morphologies (sphere, ring, disk, and rod), and composition (metal oxides, noble metal and semiconductor compounds, etc.), thereby greatly enriching the array of MJANPs. In vivo theranostic applications using the tumor-bearing mice model further demonstrated the effectiveness of these MJANPs in high-resolution multimodality imaging and high-efficiency cancer therapeutics. The ubiquitous assembly approach developed in the current study pave the way for on-demand design of high-performance Janus amphiphilic nanoparticles for various clinical diagnoses and therapeutic applications.

Synthesis and Characterization of Curcumin-Functionalized HP-ß-CD-Modified GoldMag Nanoparticles as Drug Delivery Agents.

Curcumin, a polyphenol extracted from turmeric (Curcuma longa), has emerged as a potent multimodal cancer-preventing agent. It may attenuate the spread of cancer and render chemotherapy more effective. However, curcumin is neither well absorbed nor well retained in the blood, resulting in low efficacy. In an attempt to enhance the potency and to improve the bioavailability of curcumin, new delivery agents, hydroxypropyl-beta-cyclodextrin (HP-ß-CD)-modified GoldMag nanoparticles (CD-GMNs) were designed and synthesized to incorporate curcumin. The CD-GMNs were characterized by Fourier Transform Infrared Spectroscopy (FT-IR), Thermo-gravimetric Analysis (TGA), X-ray Diffraction (XRD), Dynamic Light Scattering measurements (DLS), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometer (VSM) analyses. For the magnetic carrier of CD-GMNs, the content of HP-ß-CD was 26.9 wt%. CD-GMNs have a saturation magnetization of 22.7 emu/g with an average hydrodynamic diameter of 80 nm. The curcumin loading, encapsulation efficiency and releasing properties in vitro were also investigated. The results showed that the drug encapsulation ratio was 88% and the maximum curcumin loading capacity of CD-GMNs was 660 µg/5 mg. In vitro drug release studies showed a controlled and pH-sensitive curcumin release over a period of one week. Collectively, our data suggest that HP-ß-CD-modified GoldMag nanoparticles can be considered to form a promising delivery system for curcumin to tumor sites. Targeting can be achieved by the combined effects of the application of an external magnetic field and the effect on drug release of lower pH values often found in the tumor microenvironment.

[Recent advances in curcumin and its derivatives for treatment of liver diseases].

Curcumin is a principal polyphenolic curcuminoid extracted from turmeric rhizome, which has been used for treating inflammation of joints, ulcers, jaundice and other disorders in Asian traditional medicine. In recent years, many studies have indicated that curcumin plays important roles in treatment of liver diseases. Curcumin attenuates liver injury and non-alcoholic fatty liver disease by lowering the release of inflammation cytokines, minimizing oxidative stress, enhancing the sensitivity of insulin and altering lipid metabolism. Curcumin shows potent anti-fibrosis activity, contributing to inhibit the activation of hepatic stellate cells and reduce the deposition of extracellular matrix by its regulation of PPAR-γ, NF-ΚB and TGF-ß signaling pathways. Moreover, curcumin exhibits anti-cancer effect by inducing G2/M phase cell cycle arrest and apoptosis in several hepatoma cell lines. However, poor water solubility and low bioavailability of curcumin limit its clinical applications. To overcome its limited systemic bioavailability, many new approaches have been explored to deliver curcumin effectively. This article focuses on advances in the effects of curcumin and its derivatives for treatment of liver injury, non-alcoholic fatty liver disease, liver fibrosis and hepatocarcinoma.

Study of the Cold Curing Characteristics of Isocyanate-Modified Asphalt.

Isocyanate esters are widely recognized for their superior curing capabilities. Leveraging this attribute, the current research formulated a modified cold-mixed asphalt blend using 4,4'-methylene diphenyl diisocyanate (MDI). Tests and analyses of the MDI-modified asphalt with varying inclusion percentages of MDI revealed that a mixture containing 15% rock asphalt and 15% MDI-modified asphalt exhibited a more balanced, comprehensive performance. We also conducted an examination of the role and properties of MDI in asphalt modification using molecular dynamics simulations. The cold-curing properties of MDI-modified asphalt as compared to petroleum asphalt were evaluated based on its density, free volume analysis, cohesive energy density, and glass transition temperature. Implementing the LB-13 gradation-a cold-mixed asphalt gradation with a nominal particle size of 13.2 mm recommended by Chinese specifications-we prepared MDI-modified cold-mixed asphalt and carried out analyses of its mechanical characteristics, high-temperature performance, and water damage resistance. The results demonstrated that MDI-modified asphalt showcases excellent ductility, flexibility, and aging resistance, surpassing the performance of petroleum asphalt. The stability, high-temperature rutting, and water damage resistance of the MDI-modified cold-mixed asphalt exceeded the requirements for hot-mixed asphalt. This research provides theoretical and experimental support for isocyanate ester applications in asphalt engineering, presenting significant value for practical engineering applications.

Safety and Immunogenicity After Primary and Booster Inactivated SARS-Cov-2 Vaccination in Patients with Autoimmune Liver Diseases.

Background and Aims: SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports. However, the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases (AILD) is still unknown. Methods: Eighty-four patients with AILD were prospectively followed up after the second dose (primary) of inactivated SARS-CoV-2 vaccine. Some of them received the third dose (booster) of inactivated vaccine. Adverse events (AEs), autoimmune activation, and liver inflammation exacerbation after primary and booster vaccination were recorded. Meanwhile, dynamics of antireceptor-binding-domain IgG (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD-specific B cells responses were evaluated. Results: The overall AEs in AILD patients after primary and booster vaccination were 26.2% and 13.3%, respectively. The decrease of C3 level and increase of immunoglobulin light chain κ and λ levels were observed in AILD patients after primary vaccination, however, liver inflammation was not exacerbated, even after booster vaccination. Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination. Notably, the antibody titers were significantly elevated after booster vaccination (10-fold in anti-RBD-IgG and 7.4-fold in NAbs, respectively), which was as high as in healthy controls. Unfortunately, the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants. Changes of atypical memory B cells were inversely related to antibody levels, which indicate that the impaired immune memory was partially restored partly by the booster vaccination. Conclusions: The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.

Evaluating the protective effectiveness and risk factors of ursodeoxycholic acid on COVID-19 among outpatients.

Objective: This study aimed to assess the chemopreventive effect of ursodeoxycholic acid (UDCA) against COVID-19 and to analyze infection risk factors, symptoms, and recovery in outpatients with UDCA exposure. Methods: The study enrolled outpatients prescribed UDCA from the Second Affiliated Hospital of Chongqing Medical University, China, between 01 July 2022, and 31 December 2022. Data on demographics, comorbidities, and drug combinations were collected using electronic medical records. COVID-19 infection, symptoms, severity, prognosis, vaccinations, and UDCA administration were surveyed by telephone interviews. UDCA non-users served as controls and were matched in a 1:2 ratio with UDCA users using propensity score matching with the nearest neighbor algorithm. Infection rates, symptomatology, severity, and prognosis were compared between matched and control cohorts, and risk factors and infection and recovery symptoms were analyzed in UDCA-exposed outpatients. Results: UDCA-exposed outpatients (n = 778, 74.8%) and matched UDCA users (n = 95, 74.2%) showed significantly lower SARS-CoV-2 infection rates than control patients (n = 59, 92.2%) (p < 0.05). The matched UDCA group exhibited substantially lower fever, cough, sore throat, and fatigue rates than controls (p < 0.05). Participants with UDCA exposure generally experienced mild symptoms, while those without UDCA had moderate symptoms. The matched UDCA group also had significantly shorter durations of fever and cough (p < 0.05). Risk factors such as age over 60, less than 1 month of UDCA administration, diabetes mellitus, and coronary artery disease significantly increased SARS-CoV-2 infection rates (p < 0.05), while smoking led to a decrease (p < 0.05). Hypertension was associated with a prolonged COVID-19 recovery (p < 0.05), while smoking, vaccination, and fatty liver disease were associated with shorter recovery periods (p < 0.05). The main symptoms in the full UDCA cohort were fever, cough, and sore throat, with fatigue, cough, and hyposthenia being the most persistent. Conclusion: UDCA demonstrated chemopreventive effect against SARS-CoV-2 in outpatients by significantly reducing infection incidence and mitigating COVID-19 symptoms, severity, and recovery duration. Old age, short UDCA course, and comorbidities such as diabetes mellitus and CAD increased infection rates, while hypertension prolonged recovery. Smoking, vaccination, and fatty liver disease reduced infection rates and shortened recovery. UDCA had minimal impact on symptom types. Larger and longer-term clinical studies are needed further to assess UDCA's effectiveness in COVID-19 prevention or treatment.

Polyelectrolyte-coated gold magnetic nanoparticles for immunoassay development: toward point of care diagnostics for syphilis screening.

Immediate response for disease control relies on simple, inexpensive, and sensitive diagnostic tests, highly sought after for timely and accurate test of various diseases, including infectious diseases. Composite Fe3O4/Au nanoparticles have attracted considerable interest in diagnostic applications due to their unique physical and chemical properties. Here, we developed a simple coating procedure for gold magnetic nanoparticles (GMNs) with poly(acrylic acid) (PAA). PAA-coated GMNs (PGMNs) were stable and monodispersed and characterized by Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy, UV-visible scanning spectrophotometry, thermogravimetric analysis, and Zetasizer methodologies. For diagnostic application, we established a novel lateral flow immunoassay (LFIA) strip test system where recombinant Treponema pallidum antigens (r-Tp) were conjugated with PGMNs to construct a particle probe for detection of anti-Tp antibodies. Intriguingly, the particle probes specifically identified Tp antibodies with a detection limitation as low as 1 national clinical unit/mL (NCU/mL). An ample pool of 1020 sera samples from three independent hospitals were obtained to assess our PGMNs-based LFIA strips, which exhibited substantially high values of sensitivity and specificity for all clinical tests (higher than 97%) and, therefore, proved to be a suitable approach for syphilis screening at a point-of-care test manner.

Building nanoSPR biosensor systems based on gold magnetic composite nanoparticles.

Composite Fe3O4/Au nanoparticles are attracting considerable interest in developing visual and specific detection of biomolecular due to their unique physical and chemical properties. Here, two localize surface plasmon resonance (LSPR) probes based on Fe3O4/Au nanoparticles (nanoSPR biosensors) were fabricated by exploring 11-mercaptoundecanoic acid (MUA) and poly acrylic acid (PAA) as surface modification agents and subsequently conjugating rabbit IgG with the modified particles' surface. Comparative investigations showed the differences between MUA-particles and PAA-particles, as well as sensitivity of the two as-prepared nanoSPR biosensors when used in target goat anti-rabbit IgG colorimetric detection. Particles coated with PAA were in a better dispersion and showed an ionic independent stability, indicating PAA-particles have a potential application in colorimetric detection. In contrast, the MUA-particle probes revealed a higher sensitivity in SPR detection (50 nmol/L), and further kinetic studies showed the reactions between probes and target followed the second order and the reaction rate of MUA-probes was twice the rate of PAA-probes at the same temperature and condition. Such proof-of concept works reported here demonstrated that the protocol to build nanoSPR biosensors was favored in developing molecular probes, and the novel composite nanoparticles might serve as ideal probes for sensitive, selective and real time detection.

GW9662 ameliorates nonalcoholic steatohepatitis by inhibiting the PPARγ/CD36 pathway and altering the gut microbiota.

BACKGROUND & AIMS: Peroxisome proliferator-activated receptors (PPARs) are currently among the most focused-on therapeutic targets for non-alcoholic steatohepatitis (NASH), although no clinical transformation has been achieved to date. In this study, we aimed to evaluate the effects of GW9662 on choline-deficient, L-amino acid-defined high-fat diet (CDAA-HFD)-induced NASH mice and reveal the mechanism underlying this effect. METHODS: GW9662 (1 mg/kg) was administered in CDAA-HFD mouse model of NASH. The effect of GW9662 on hepatic lipid metabolism was investigated using liver RNA-seq and HepG2 cells induced by oleic acid and palmitic acid. In addition, 16S rRNA gene sequencing was performed to analyze the effects of GW9662 on the composition and function of the fecal microbiota. RESULTS: GW9662 improved the CDAA-HFD caused elevation in the levels of ALT, AST, hepatic free fatty acids and triglycerides. The liver pathological analysis indicated that GW9662 alleviated the hepatic steatosis and fibrosis. The NAFLD activity score and RNA-Seq revealed that GW9662 mainly regulated the fatty acids transport and lipid synthesis by inhibiting PPARγ, CD36, FABP1, FASN, and SCD1, and through the up-regulation of PPARα. Moreover, GW9662 reduced the epididymal fat weight. GW9662 reversed the gut microbiota disorder by increasing the abundance of the beneficial bacteria Dubosiella and Lactobacillus and decreasing the abundance of harmful bacteria Lachnospiraceae_NK4A136_group, Helicobacteraceae, Desulfovibriaceae, and Rickenaceae. CONCLUSIONS: GW9662 ameliorated lipid metabolism by inhibiting the PPARγ/CD36 pathway and altering the composition of the gut microbiota in NASH mice. Therefore, the PPARγ antagonist GW9662 deserves more attention as a potential therapeutic agent for NASH.

Safety and immunogenicity of the third (booster) dose of inactivated and recombinant protein SARS-CoV-2 vaccine for patients with endocrine-related cancer.

Background: Our study aimed to evaluate the safety and immunogenicity of the third (booster) dose of the COVID-19 vaccine for patients with endocrine-related cancers. Methods: This observational study involved 94 breast cancer patients, 92 thyroid cancer patients, and 123 healthy individuals who had received the third (booster) dose of the COVID-19 vaccine. Data on the adverse effects, serum anti-receptor binding domain (RBD)-immunoglobulin (Ig) G, and neutralizing antibodies (NAbs) were collected prospectively. Results: The serum anti-RBD-IgG and NAb titers were significantly lower for the patients with endocrine-related malignancies than for the healthy controls (3.01 [IQR: 1.11-6.70] vs. 4.19 [1.95-9.11], p = 0.001; 0.23 [0.11-0.52] vs. 0.41 [0.22-0.78], p = 0.001), and the seroconversion rates of anti-RBD-IgG and NAbs showed similar results. The serum antibody titers and seroconversion rates were significantly lower for patients aged ≥65 years with endocrine-related cancers, but there were no significant differences related to gender, vaccine type, or cancer type. Subgroup analysis showed that the antibody titers and seroconversion rates were significantly lower for patients with intermediate to advanced breast cancer, HR-/Her2+ breast cancer, and breast cancer undergoing treatment than for healthy controls. In contrast, breast cancer patients who completed their treatment and those who received endocrine therapy after completing their treatment were not significantly different from healthy controls. The NAbs titers and seroconversion rates were significantly lower for patients with primary thyroid cancer (0.19 [IQR: 0.10-0.46] vs. 0.41 [0.22-0.78], p = 0.003; 55.9 vs. 84.9%, p < 0.001); the seroconversion rates were significantly higher for the patients with combined Hashimoto's thyroiditis than for those without it. Multiple linear regression showed that patients aged ≥65 years who were receiving treatment were at risk of having lower antibody levels. Conclusion: The third (booster) dose of the COVID-19 vaccine is safe and well-tolerated. Our data support a third (booster) dose of the SARS-CoV-2 vaccine for breast and thyroid cancer patients. Breast cancer patients aged ≥65 years who are receiving treatment should be more protected, while thyroid cancer and breast cancer patients who have completed their treatment can be vaccinated like the general population.