Immune Persistence following Primary Immunization and the Immunogenicity and Safety of a Booster Dose of a Multidose Sabin Strain-Based Inactivated Polio Vaccine in Infants Aged 18 Months.

BACKGROUND: The multidose Sabin-strain inactivated poliovirus vaccine (sIPV) has the potential to significantly aid in the eradication of poliomyelitis, particularly in low- and middle-income countries. As part of a phase III clinical trial in which infants were given three doses of primary immunization at 2, 3, and 4 months of age, this study aimed to evaluate immune persistence following primary immunization, as well as the safety and immunogenicity of a booster of the 5-dose sIPV in infants aged 18 months. METHODS: Infants aged 18 months were given one booster dose of 5-dose sIPV in stage one, which was open-label. Unblinding was performed for stage two after completing primary immunization, which was randomized, blinded, and controlled; infants aged 18 months in the test group I-III, IPV group, and single-dose sIPV group were given one booster dose of 5-dose sIPV, conventional IPV, and single-dose sIPV, respectively, in stage two. RESULTS: This study included 1438 infants in the immune persistence and safety set and 1387 infants in the booster per-protocol set. Fourteen months after primary immunization, the seropositivity rates (≥1:8) for types 1-3 were 100%, 99.88%, and 99.53% in the 5-dose sIPV groups; 100%, 98.97%, and 97.23% in the IPV group; and 99.66%, 100%, and 99.66% in the single-dose sIPV group. A total of 30 days after booster immunization, the seropositivity rates (≥1:8) of 3 serotypes in all the groups reached 100%. The geometric mean titers of neutralizing antibodies for types 1-3 in the 5-dose sIPV group were 9962.89, 10273, and 7870.21, with geometric mean increases of 15.76, 33.15, and 24.5, compared to the pre-booster level. The overall incidence of adverse reactions was 8.97%, with fever being the most common, observed at rates of 7.1%, 5.52%, and 7.96% in the 5-dose sIPV, IPV, and single-dose groups, respectively (p = 0.4845). CONCLUSIONS: The 5-dose sIPV has shown promising immune persistence and robust immune response following a booster immunization, coupled with an acceptable safety profile.

Construction of a g-C3N4/Bi(OH)3 Heterojunction for the Enhancement of Visible Light Photocatalytic Antibacterial Activity.

Photocatalytic technology has been recently conducted to remove microbial contamination due to its unique features of nontoxic by-products, low cost, negligible microbial resistance and broad-spectrum elimination capacity. Herein, a novel two dimensional (2D) g-C3N4/Bi(OH)3 (CNB) heterojunction was fabricated byincorporating Bi(OH)3 (BOH) nanoparticles with g-C3N4 (CN) nanosheets. This CNB heterojunction exhibited high photocatalytic antibacterial efficiency (99.3%) against Escherichia coli (E. coli) under visible light irradiation, which was 4.3 and 3.4 times that of BOH (23.0%) and CN (28.0%), respectively. The increase in specific surface area, ultra-thin layered structure, construction of a heterojunction and enhancement of visible light absorption were conducive to facilitating the separation and transfer of photoinduced charge carriers. Live/dead cell staining, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) assays and scanning electron microscopy (SEM) have been implemented to investigate the damage to the cell membrane and the leakage of the intracellular protein in the photocatalytic antibacterial process. The e-, h+ and O2•- were the active species involved in this process. This study proposed an appropriate photocatalyst for efficient treatment of bacterial contamination.

Immunogenicity and safety of a live-attenuated varicella vaccine in a healthy population aged 13 years and older: A randomized, double-blind, controlled study.

OBJECTIVES: Vaccines for prevention against varicella are important for adolescents and adults, who have an increased risk of severe varicella. This study aimed to evaluate the immunogenicity and safety of a two-dose immunization schedule of a live-attenuated varicella vaccine (VarV) manufactured by Sinovac (Dalian) in healthy adolescents and adults. METHODS: A randomized, double-blind, controlled clinical trial was conducted in healthy population aged ≥ 13 years old in China. Participants in block 1 were randomly assigned (1:1) to receive two doses of either the test vaccine or an active control vaccine, administered 4, 6 or 8 weeks apart. Participants in block 2 were randomly assigned (2:1) to receive two doses of test vaccine or placebo, administered 10 weeks apart. The primary immunogenicity endpoint was the seroconversion rates and GMTs of varicella zoster virus (VZV) antibodies measured by fluorescent-antibody-to-membrane-antigen (FAMA) 4 weeks post-immunization. The primary safety endpoint was the incidence of adverse reactions within 4 weeks after each dose. RESULTS: A total of 2398 participants were enrolled. The seroconversion rates of VZV antibodies were 79.55 % in the test group and 76.41 % in the active control group respectively 4 weeks after two doses of pooled schedule, with the difference of 3.14 % (95 %CI: -0.69 %, 6.97 %). The GMTs were 1:162.07 and 1:160.04 respectively, with the ratio of 1.013 (95 %CI: 0.910, 1.127). Both the seroconversion rates and GMTs reached the prespecified non-inferiority criteria. Two-dose schedule with an interval of 10 weeks could also induce high immune responses, with a seroconversion rate of 83.22 % and a GMT of 1:160.38 in the test group. Safety profiles were similar among the test group, active control group and placebo group. CONCLUSION: VarV, manufactured by Sinovac (Dalian), demonstrated higher immune response and better flexibility in the immunization schedule among heathy population aged 13 years and older, without increased safety risk.

A cross-sectional study of appropriateness evaluation of anticoagulation therapy for inpatients with nonvalvular atrial fibrillation.

Background: Oral anticoagulants (OACs) are essential for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, the appropriateness of anticoagulation treatment in locally practice remains unclear. This study evaluated compliance with anticoagulation therapy concerning the guidelines and drug labels in patients with NVAF. Methods: Hospitalized patients diagnosed with NVAF between 1 November 2020, and 31 December 2021, were retrospectively enrolled. The appropriateness of anticoagulation regimens at discharge was evaluated based on a flowchart designed according to atrial fibrillation (AF) guidelines and medication labels. Furthermore, we explored factors potentially influencing the "no-use of OACs" using binary logistic regression and verified anticoagulation-related issues through a physician questionnaire. Results: A total of 536 patients were enrolled in this study, including 254 patients (47.4%) with inappropriate anticoagulation regimens. 112 patients (20.9%) were categorized as "underdosing-use of OACs," 134 (25%) who needed anticoagulation therapy were "no-use of OACs" and eight (1.5%) were "over-use of OACs." The results of a binary logistic regression analysis showed that paroxysmal AF (odds ratio [OR], 7.74; 95% confidence interval [CI], 4.57-13.10), increased blood creatinine levels (OR, 1.88; 95% CI, 1.11-3.16), hospitalized pacemaker implantation (OR, 6.76; 95% CI, 2.67-17.11), percutaneous coronary intervention (OR, 3.35; 95% CI, 1.44-7.80), and an increased HAS-BLED score (OR, 1.62; 95% CI, 1.11-2.35) were associated with "no-use of OACs" in patients with NVAF who had indications for anticoagulation therapy. Conclusion: For patients with NVAF with severe renal dysfunction and paroxysmal AF, anticoagulation therapy was inadequate. The underdosing-use of OACs in patients with NVAF was frequently observed. We recommend an anticoagulation management team to tailor anticoagulation regimens to suit each patient's needs.

Safety, tolerability, and immunogenicity of a CpG/Alum adjuvanted SARS-CoV-2 recombinant protein vaccine (ZR202-CoV) in healthy adults: Preliminary report of a phase 1, randomized, double-blind, placebo-controlled, dose-escalation trial.

This was a phase 1 dose-escalation study of ZR202-CoV, a recombinant protein vaccine candidate containing a pre-fusion format of the spike (S)-protein (S-trimer) combined with the dual-adjuvant system of Alum/CpG. A total of 230 participants were screened and 72 healthy adults aged 18-59 years were enrolled and randomized to receive two doses at a 28-day interval of three different ZR202-CoV formulations or normal saline. We assessed the safety for 28 days after each vaccination and collected blood samples for immunogenicity evaluation. All formulations of ZR202-CoV were well-tolerated, with no observed solicited adverse events ≥ Grade 3 within 7 days after vaccination. No unsolicited adverse events ≥ Grade 3, or serious adverse events related to vaccination occurred as determined by the investigator. After the first dose, detectable immune responses were observed in all subjects. All subjects that received ZR202-CoV seroconverted at 14 days after the second dose by S-binding IgG antibody, pseudovirus and live-virus based neutralizing antibody assays. S-binding response (GMCs: 2708.7 ~ 4050.0 BAU/mL) and neutralizing activity by pseudovirus (GMCs: 363.1 ~ 627.0 IU/mL) and live virus SARS-CoV-2 (GMT: 101.7 ~ 175.0) peaked at 14 days after the second dose of ZR202-CoV. The magnitudes of immune responses compared favorably with COVID-19 vaccines with reported protective efficacy.

Self-assembled, hemin-functionalized peptide nanotubes: an innovative strategy for detecting glutathione and glucose molecules with peroxidase-like activity.

Accurately detecting dynamic changes in bioactive small molecules in real-time is very challenging. In this study, a hemin-based peptide assembly was rationally designed for the colorimetric detection of active small molecules. Hemin-functionalized peptide nanotubes were obtained through the direct incubation of hemin (hemin@PNTs) and peptide nanotubes (PNTs) or were coassembled with the heptapeptide Ac-KLVFFAL-NH2 via electrostatic, π-π stacking, and hydrophobic interactions (hemin-PNTs). This new substance is significant because it exhibits the benefits of both hemin and PNTs as well as some special qualities. First, hemin-PNTs exhibited higher intrinsic peroxidase-like activity, which, in the presence of H2O2, could catalyze the oxidation of the substrate 3,3',5,5'-tetramethylbenzidine (TMB) to yield a typical blue solution after 10 min at 25 ℃. Second, hemin-PNTs showed significantly higher activity than that of hemin, PNTs alone, or hemin@PNTs. Hemin-PNTs with a 20.0% hemin content may cooperate to improve catalytic activity. The catalytic activity was dependent on the reaction temperature, pH, reaction time, and H2O2 concentration. The nature of the TMB-catalyzed reaction may arise from the production of hydroxyl radicals. Fluorescence analysis was used to demonstrate the catalytic mechanism. According to this investigation, a new highly selective and sensitive colorimetric technique for detecting glutathione (GSH), L-cysteine, and glucose was established. The strategy demonstrated excellent sensitivity for GSH in the range of 1 to 30 µM with a 0.51 µM detection limit. Importantly, this glucose detection technique, which employs glucose oxidase and hemin-PNTs, is simple and inexpensive, with a 0.1 µM to 1.0 mM linear range and a 15.2 µM detection limit. Because of their low cost and high catalytic activity, hemin-PNTs are an excellent choice for biocatalysts in a diverse range of potential applications, including applications in clinical diagnostics, environmental chemistry, and biotechnology.

Safety, immunogenicity, and lot-to-lot consistency of a multidose Sabin strain-based inactivated polio vaccine: a phase III, randomized, blinded, positive-control clinical trial in infants aged 2 months.

OBJECTIVES: To evaluate the safety, immunogenicity, and lot-to-lot consistency of Sabin strain-based inactivated polio vaccine (sIPV) in a five-dose vial presentation. METHODS: Stage I was an open-label safety observation, in which 72 healthy subjects (including 24 adults, children, and infants each) were given one or three doses of the five-dose vial sIPV; stage II was a randomized, blinded, and positive-control study, in which 1500 infants were randomized at the ratio of 1: 1: 1: 1: 1 into five groups to receive either three doses of the five-dose sIPV three lots, a conventional inactivated poliovirus vaccine, or a single-dose sIPV as controls, for primary immunization. Safety, immunogenicity, and lot-to-lot consistency were assessed. RESULTS: Among 1456 subjects who completed the primary immunization, the geometric mean titer ratios of types 1, 2, and 3 of each pair of lots were all within the equivalence criteria margin (0.67-1.50). The seroconversion rates of types 1, 2, and 3 in the combined test group were 98.02%, 94.07%, and 98.77%, respectively, which were noninferior to both control groups. The overall incidence of adverse reactions was 29.68% and erythema was the most common adverse reaction with incidences of 10.47%,9.33%, and 9.73% in the combined test group and control groups (P >0.05). CONCLUSION: The five-dose sIPV demonstrated good safety, immunogenicity, and lot-to-lot consistency.

The Synergistic Effect of Adsorption-Photocatalysis for Removal of Organic Pollutants on Mesoporous Cu2V2O7/Cu3V2O8/g-C3N4 Heterojunction.

Cu2V2O7/Cu3V2O8/g-C3N4 heterojunctions (CVCs) were prepared successfully by the reheating synthesis method. The thermal etching process increased the specific surface area. The formation of heterojunctions enhanced the visible light absorption and improved the separation efficiency of photoinduced charge carriers. Therefore, CVCs exhibited superior adsorption capacity and photocatalytic performance in comparison with pristine g-C3N4 (CN). CVC-2 (containing 2 wt% of Cu2V2O7/Cu3V2O8) possessed the best synergistic removal efficiency for removal of dyes and antibiotics, in which 96.2% of methylene blue (MB), 97.3% of rhodamine B (RhB), 83.0% of ciprofloxacin (CIP), 86.0% of tetracycline (TC) and 80.5% of oxytetracycline (OTC) were eliminated by the adsorption and photocatalysis synergistic effect under visible light irradiation. The pseudo first order rate constants of MB and RhB photocatalytic degradation on CVC-2 were 3 times and 10 times that of pristine CN. For photocatalytic degradation of CIP, TC and OTC, it was 3.6, 1.8 and 6.1 times that of CN. DRS, XPS VB and ESR results suggested that CVCs had the characteristics of a Z-scheme photocatalytic system. This study provides a reliable reference for the treatment of real wastewater by the adsorption and photocatalysis synergistic process.

Effective Removal of Methylene Blue on EuVO4/g-C3N4 Mesoporous Nanosheets via Coupling Adsorption and Photocatalysis.

In this study, we first manufactured ultrathin g-C3N4 (CN) nanosheets by thermal etching and ultrasonic techniques. Then, EuVO4 (EV) nanoparticles were loaded onto CN nanosheets to form EuVO4/g-C3N4 heterojunctions (EVCs). The ultrathin and porous structure of the EVCs increased the specific surface area and reaction active sites. The formation of the heterostructure extended visible light absorption and accelerated the separation of charge carriers. These two factors were advantageous to promote the synergistic effect of adsorption and photocatalysis, and ultimately enhanced the adsorption capability and photocatalytic removal efficiency of methylene blue (MB). EVC-2 (2 wt% of EV) exhibited the highest adsorption and photocatalytic performance. Almost 100% of MB was eliminated via the adsorption-photocatalysis synergistic process over EVC-2. The MB adsorption capability of EVC-2 was 6.2 times that of CN, and the zero-orderreaction rate constant was 5 times that of CN. The MB adsorption on EVC-2 followed the pseudo second-order kinetics model and the adsorption isotherm data complied with the Langmuir isotherm model. The photocatalytic degradation data of MB on EVC-2 obeyed the zero-order kinetics equation in 0-10 min and abided by the first-order kinetics equation for10-30 min. This study provided a promising EVC heterojunctions with superior synergetic effect of adsorption and photocatalysis for the potential application in wastewater treatment.

New Protocol of Intermittent Androgen Deprivation Therapy for Patients With Metastatic Prostate Cancer: A Retrospective Study.

BACKGROUND: The optimal points for halting and resuming treatment in intermittent androgen deprivation therapy (IADT) for metastatic prostate cancer patients are controversial. PATIENTS AND METHODS: In the 65 metastatic prostate cancer patients in group 1, androgen deprivation therapy was stopped when prostate-specific antigen (PSA) levels reached a nadir and was resumed when PSA levels doubled and ≥ 1.0 ng/mL (new protocol). In the 62 patients in group 2, androgen deprivation therapy was stopped 3 months after PSA = 0.2 ng/mL and resumed at PSA ≥ 4.0 ng/mL (Chinese Urological Association guideline). The total IADT duration, overall on-treatment and off-treatment time, tumor clinical progression ratio, performance status improvement, and treatment-related adverse effects were retrospectively analyzed. RESULTS: In groups 1 and 2, the median total IADT durations were 51 and 46.5 months (significant difference, P = .006), median overall on-treatment times were 28 and 27.5 months (no significant difference, P > .05), and median overall off-treatment times were 23 and 19 months (significant difference, P < .001), respectively. Multivariate Cox regression analysis indicated that patients in group 1 had significantly higher progression-free-survival (hazard ratio, 0.634; P = .014). Two cases of clinical progression occurred group 1 and 5 in group 2; there was no significant difference (P > .05). There were no significant differences between the groups in terms of performance status improvement and treatment-related adverse effects. CONCLUSION: The new protocol was found to be beneficial, showing less biochemical/clinical progression, satisfactory performance status, and acceptable treatment-related adverse effects.

Qizhufang (ZSF) Ameliorates Hepatic Iron Overload via Signal Transducer and Activator of Transcription 3 (STAT3) Pathway.

BACKGROUND Iron overload is a prominent characteristic of liver injury, but there is no effective treatment at present. Qizhufang (ZSF) is a Chinese herbal formula showed anti-HBV activities, improved liver function, and anti-fibrosis effect. ZSF showed a series of liver-protection functions, but whether ZSF can relieve hepatic iron overload is still unclear. MATERIAL AND METHODS Ferric ammonium citrate (FAC) was used to construct iron-overloaded LO2 cells. The cell apoptosis and proliferation were measured by flow cytometry and CCK-8 assay, respectively. ROS level was analyzed by fluorescence probe. RNA and protein expressions were assessed by real-time PCR and Western blot. RESULTS FAC upregulated apoptosis rate, ROS level, and expression of hepcidin and p-STAT3, but suppressed proliferation and expression of DMT1, FPN1, and CP in LO2 cells. However, Qizhufang (ZSF) reversed the effect of FAC. We also found that hepcidin overexpression suppressed the expressions of DMT1, FPN1, and CP, which were reversed by ZSF. Additionally, STAT3 inhibitor AG490 suppressed hepcidin expression. Moreover, exogenous IL-6 reversed the effect of ZSF on apoptosis rate, ROS level, and the expression of hepcidin, DMT1, FNP1, CP, and p-STAT3. CONCLUSIONS Qizhufang (ZSF) can ameliorate iron overload-induced injury by suppressing hepcidin via the STAT3 pathway in LO2 cells.

The Composition-Dependent Photoluminescence Properties of Non-Stoichiometric ZnxAgyInS1.5+x+0.5y Nanocrystals.

A facile hot injection approach to synthesize high-quality non-stoichiometric ZnxAgyInS1.5+x+0.5y nanocrystals (NCs) in the size range of 2.8-3.1 nm was presented. The fluorescence spectra had single band gap features, and indicated the formation of alloy states rather than simple composite structures. The chemical compositions, photoluminescence (PL) emission wavelengths, and quantum yields of ZnxAgyInS1.5+x+0.5y nanocrystals were significantly influenced by the concentration of an organic capping agent. The appropriate proportion of 1-dodecanthiol in the precursor prevented the precipitation, increased the fluorescence quantum yield, and improved their optical properties. The proper ratio of capping agent allowed Zn, Ag, and In to form a better crystallinity and compositional homogeneity of ZnxAgyInS1.5+x+0.5y nanocrystals. The photoluminescence was tunable from blue to red in the range of 450-700 nm as the Ag content changed independently. The PL and absorption spectra of ZnxAgyInS1.5+x+0.5y nanocrystals showed a significant blue shift with the decrease of Ag content in the precursor. As there were no obvious differences on the average particle sizes of ZnxAgyInS1.5+x+0.5y samples, these results fully revealed the composition-dependent photoluminescence properties of ZnxAgyInS1.5+x+0.5y nanocrystals. The relative quantum yield reached 35%. The fluorescence lifetimes (τ1=115-148 ns and τ2=455-483 ns) were analogous to those of AgInS2 and (AgIn)xZn2(1-x)S2.

[Dynamic change in the gene expression profile of rat benign prostate hyperplasia tissue after complete denervation].

OBJECTIVE: To investigate the dynamic change in the gene expression profile of the rat BPH tissue with progressive atrophy after complete denervation. METHODS: Twelve 29-week-old male rats with spontaneous hypertension and spontaneously developed BPH were used for this study, of which 3 were included in the control (C) group and the other 9 underwent complete denervation of the prostate. At 3, 7 and 11 days after operation (the D3, D7 and D11 groups), all the rats were sacrificed and their ventral prostatic lobes harvested for histopathological examination and RNA extraction, and the RNA samples were subjected to whole genome microarray of the expression profile, followed by real-time RT-PCR validation and bioinformatics analysis. RESULTS: Progressive atrophy of the BPH tissue was observed in the rats after complete denervation. Whole genome microarray of the expression profile was successfully performed for all the samples, and its reliability validated by real-time RT-PCR of 6 differentially expressed genes selected randomly. Hierarchical clustering analysis showed 108 up-regulated and 175 down-regulated genes in the differentially expressed ones between the D3 and C groups, 462 up-regulated and 189 down-regulated in those between the D7 and C groups, and 548 up-regulated and 256 down-regulated in those between the D11 and C groups. GO functional enrichment analysis indicated that the genes in each differentially expressed gene set participated in hundreds of molecular functions, biological processes and cellular components, while pathway enrichment analysis showed their involvement in hundreds of signaling pathways, of which many were enriched simultaneously in each differentially expressed gene set and ranked as the most enriched ones, and most of the genes involved were up-regulated and related with the activation of the complement system. CONCLUSIONS: Large numbers of abnormally expressed genes are involved in the progressive atrophy of rat BPH tissue after complete denervation, and these genes participate in hundreds of molecular functions, biological progresses, cellular components and signaling pathways. Abnormal activation of the complement system may play an important role in the progressive atrophy of the BPH tissue.

Species of Neoperla (Plecoptera: Perlidae) from Henan Province, China.

A new species, Neoperla jigongshana Li & Li, sp. nov., is proposed from Henan Province, China and compared with related congeners. Two additional species, N. cavaleriei (Navás, 1922) and N. forcipata Yang & Yang, 1992, are reported from the Province for the first time and descriptions of female and egg of N. baotianmana Li & Wang, 2011 are also presented. A provisional key to the known species of the Henan Province is presented.