High-robustness autofocusing method in the microscope with laser-based arrayed spots.

Accurate and rapid autofocus technology plays a crucial role in various fields, including automatic optical inspection technology, bio-chips scanning, and semiconductor manufacturing. The current photoelectric autofocus methods have limitations because of detecting the focal plane solely at the center of the microscope field of view. In the application of Stereo-seq the risk of autofocus errors will be increased, which have reduced the robustness of the system, like when the surface of the tested samples are wrinkling and inconsistent thickness, or the detection spot is at the edge of the sample. To enhance the robustness of the autofocus system and mitigate the constraints of the photoelectric autofocus methods, the laser-based arrayed spots photoelectric autofocus method has been proposed. To achieve the uniform light splitting, a 2D-Dammann grating is incorporated into the optical path of the autofocus system, resulting in the formation of an n × n arrayed spots on the surface of the sample. Through experimental verification, it has been demonstrated that this method can achieve the autofocus range of ±100µm and the autofocus accuracy of ±1/4 DOF when applied to a microscope equipped with a 10× objective lens, thereby satisfying the requirements for microscopic focusing. The arrayed light autofocus method devised in this study presents what we believe is a novel research concept for active autofocus detection and holds significant application value.

Chromone-deferiprone hybrids as novel MAO-B inhibitors and iron chelators for the treatment of Alzheimer's disease.

A series of chromone-deferiprone hybrids were designed, synthesized, and evaluated as inhibitors of human monoamine oxidase B (hMAO-B) with iron-chelating activity for the treatment of Alzheimer's disease (AD). The majority exhibited moderate inhibitory activity towards hMAO-B and potent iron-chelating properties. Particularly, compound 25c demonstrated remarkable selectivity against hMAO-B with an IC50 value of 1.58 µM and potent iron-chelating ability (pFe3+ = 18.79) comparable to that of deferiprone (pFe3+ = 17.90). Molecular modeling and kinetic studies showed that 25c functions as a non-competitive hMAO-B inhibitor. According to the predicted results, compound 25c can penetrate the blood-brain barrier (BBB). Additionally, it has been proved to display significant antioxidant activity and the ability to inhibit neuronal ferroptosis. More importantly, compound 25c reduced the cognitive impairment induced by scopolamine and showed significant non-toxicity in short-term toxicity assays. In summary, compound 25c was identified as a potential anti-AD agent with hMAO-B inhibitory, iron-chelating and anti-ferroptosis activities.

Molecular characterization and antimicrobial activity of NK-lysin in black scraper (Thamnaconus modestus).

NK-lysin (NKL) is a positively charged antimicrobial peptide with broad-spectrum bactericidal activities. In this study, the cDNA sequence of NKL (TmNKL) from black scraper (Thamnaconus modestus) was cloned, which encodes a predicted polypeptide of 150 amino acids that contains a surfactant protein B domain with three disulfide bonds. Phylogenetically, TmNKL was most closely related to its teleost counterpart from tiger puffer (Takifugu rubripes). Expression analysis demonstrated that TmNKL transcripts were constitutively expressed in all tested tissues, with the highest expression levels in the gills. Its expression was significantly upregulated in the gills, head kidney, and spleen after infection with Vibrio parahaemolyticus. A linear peptide (TmNKLP40L) and a disulfide-type peptide (TmNKLP40O) were further synthesized and results showed that disulfide bonds are not essential for bactericidal activities of TmNKL, and that both forms of TmNKL exhibited potent bactericidal activities against 4 gram- negative bacteria, including V. parahaemolyticus, V. alginolyticus, Edwardsiella tarda, and V. harveyi. Observed antimicrobial activities are likely due to the effects of TmNKLP40L and TmNKLP40O treatment on disrupting the integrity of both inner and outer membrane of V. parahaemolyticus, resulting in hydrolysis of bacterial genomic DNA. Damaged cell membranes and leakage of intracellular contents were further confirmed using scanning and transmission microscopy. Moreover, administration of 1.0 µg/g TmNKLP40L or TmNKLP40O significantly decreased bacterial load in tissues and thus, pronouncedly enhanced the survival of V. parahaemolyticus-infected fish. Overall, our results demonstrated that TmNKL is a potent innate effector and provides protective effects against bacterial infection.

Effect of copper sulphate on Cryptocaryon irritans based on metabolome analysis.

Cryptocaryon irritans is one of the most harmful marine parasites in mariculture. Copper sulphate is often used to kill parasites and the influence of copper sulphate on the tomont stage of C. irritans was explored in this study. The results showed that excystment rate was not significantly affected when tomonts were exposed to 5 mg/L (76.7%) and 10 mg/L (78.9%) of copper sulphate for 3 h. However, excystment rate was significantly inhibited when exposed to 15 mg/L (33.3%) for 3 h and 5 mg/L (28.9%), 10 mg/L (33.3%) and 15 mg/L (33.3%) for 6 h. After treatment with high concentrations of copper sulphate, the interior of the tomonts was fuzzy under the microscope, and the division process could not be observed. Metabolomic results combined with preliminary transcriptome analysis results showed that the tomonts were induced to produce linoleate, riboflavin, inositol and other substances under the stress of Cu2+ , which affected the antioxidant mechanism of the body. Using MDA content determination and antioxidant enzyme activity analysis, copper sulphate was found to cause oxidative damage to tomonts by affecting the generation of metabolites, leading to the death of tomonts.

Efficacy evaluation of direct antiviral drugs against hepatitis B virus in improving the degree of liver fibrosis.

Introduction: The aim of the study was to find an ideal index reflecting inflammation and fibrosis for patients after antiviral treatment, and compare it with imaging examination (liver stiffness measurement - LSM) and traditional liver fibrosis models (APRI and FIB-4). Material and methods: A total of 77 chronic hepatitis B (CHB) patients who achieved a sustained virological response (SVR) after entecavir (ETV) treatment were included, and the changes of various clinical indicators before and after treatment were compared. Results: After 78 weeks of ETV treatment, WBC and PLT of 77 patients were significantly increased, while ALT, AST and total bilirubin were significantly decreased (p < 0.05). There was no significant difference in serum creatinine (Cr) or blood urea nitrogen (BUN) compared to the values before treatment (p > 0.05). The three non-invasive liver fibrosis indexes, namely, LSM, APRI and FIB-4, were significantly decreased in 77 patients compared to the values before treatment (p < 0.001). Conclusions: Acoustic radiation force impulse (ARFI), fibrosis-4 (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI) have a high consistency with the grading of liver fibrosis, and can be used to evaluate the severity of liver fibrosis. Among them, ARFI has good diagnostic value for the classification of different degrees of liver fibrosis and the best diagnostic accuracy.

Deficiency of canonical Wnt/ß-catenin signalling in hepatic dendritic cells triggers autoimmune hepatitis.

BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease manifested with the aberrant activation of hepatic dendritic cells (HDCs) and the subsequent breakdown of immune homeostasis. As an important player, HDC maintains immunological balance between tolerance to self-antigens versus destruction against pathogens in liver. However, the intracellular signalling networks that program HDC remain unclear. We have now found the role of canonical Wnt/ß-catenin signalling in HDCs. METHODS: Liver sections from AIH patients and healthy subjects were stained for the markers of Wnt/ß-catenin signalling. Concanavalin A (ConA) and HDC/Hepa1-6 vaccine-induced AIH mouse models were examined for liver injury, inflammation and immune cell functions by serum biochemistry, histology, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and flow cytometry analysis. Wnt/ß-catenin signalling expression was measured using immunoblot and qRT-PCR. RESULTS: Canonical Wnt/ß-catenin signalling in HDC is deficient in AIH patients and a mouse model, which coincides with the immunogenic function of HDCs. Furthermore, Wnt ligand engagement reactivates Wnt/ß-catenin signalling and recovers the immunoregulatory phenotype of HDCs, in turn alleviating the severity of AIH. Likewise, pharmacologic activation of Wnt/ß-catenin signalling attenuates AIH progression. CONCLUSIONS: We report here that the constitutively active canonical Wnt/ß-catenin signalling confers HDCs tolerogenicity under steady-state conditions. Deficiency of this pathway gives rise to T cell-mediated immune response and incidence of AIH. It may act as a new pathogenesis and treatment target for AIH.

Dietary supplementation of drumstick tree, Moringa oleifera, improves mucosal immune response in skin and gills of seabream, Sparus aurata, and attenuates the effect of hydrogen peroxide exposure.

In aquatic animals, the mucosal barrier is the first line of innate immune defence against external chemicals and pathogens. In this study, the effects of dietary Moringa oleifera leaf (MOL) supplementation on skin and gill mucosal immunity, antioxidants and stress responses were evaluated in seabream (Sparus aurata) fingerlings exposed to hydrogen peroxide (H2O2). A total of 144 specimens (10.11 ± 0.41 g) were divided into four treatments (three replicates per treatment contained 12 specimens each) and fed a non-supplemented control diet or a 1, 2.5 or 5% MOL-supplemented diet. After three weeks of feeding, six specimens from each aquarium were sampled for blood, mucus and tissues. The other six fish in each aquarium were subjected to H2O2 exposure. The results revealed that MOL did not negatively affect either cortisol or glucose levels. MOL supplementation significantly (P < 0.05) improved skin mucosal immunity-related characteristics, including phosphatase, peroxidase and lysozyme activity and IgM levels. Additionally, MOL upregulated the expression of antioxidant genes (sod and cat), an anti-inflammatory gene (tgf-ß), tight junction protein genes (occludin and zo-1), c3, and igm in both the skin and gills. However, H2O2 exposure significantly (P < 0.05) increased both cortisol and glucose levels and disrupted skin mucosal immune function by significantly (P < 0.05) decreasing phosphatase, peroxidase, protease, antiprotease and lysozyme activity and IgM levels. H2O2 exposure severely decreased the mRNA levels of the studied genes. MOL dietary supplementation at the 5% level successfully attenuated the negative effects of H2O2 on the mucosal immune response in both the skin and gills. In conclusion, dietary MOL supplementation at the 5% level is recommended to improve S. aurata mucosal immune function under both normal and stress conditions. Additionally, exposure to H2O2 disrupts the mucosal immunity of fish. This contributes knowledge on the routes involved in mucosal innate immunity and could help to understand the fish resistance against chemicals exposure. Graphical abstract.

[UPLC quantitative fingerprint research on Gardeniae Fructus based on chemical pattern recognition technology].

Twenty-six batches of Gardeniae Fructus from different producing area were collected for the development of the fingerprint, and the main components of Gardeniae Fructus were identified by liquid chromatography-mass spectrometry. The producing areas of Gardeniae Fructus were distinguished by chemical pattern recognition technology, and the index components of Gardeniae Fructus were quantitated. An UPLC wavelength switching method was adopted, and the separation was carried out on a Waters Acquity UPLC HASS C_(18)(2.1 mm×100 mm, 1.7 µm) column using the mobile phase of acetonitrile-0.5% formic acid water for gradient elution. Principal component analysis(PCA) and orthogonal partial least square discriminant analysis(OPLS-DA) were used for the data ana-lysis. The results showed that the similarity of 26 batches of Gardeniae Fructus was more than 0.89, and ten common peaks were defined. Sixteen compounds including monoterpenes, iridoids and diterpenoids were identified by reference identification, literature comparison and high-resolution mass spectrometry data analysis. The distinguishment of origin of Gardeniae Fructus was realized by PCA and OPLS-DA analysis, and two quality differential markers were screened as geniposide and crocin Ⅰ. The contents of crocin Ⅰ, crocin Ⅱ and geniposide in Gardeniae Fructus from different places were different. These results will provide reference for the geographical origin traceability of Gardeniae Fructus.

TXNIP knockdown alleviates hepatocyte ischemia reperfusion injury through preventing p38/JNK pathway activation.

Hepatic ischemia and reperfusion (I/R) injury is a major cause of liver damage during liver transplantation, resection surgery, shock, and trauma. It has been reported that TXNIP expression was upregulated in a rat model of hepatic I/R injury. However, the role of TXNIP in the hepatic I/R injury is little known. In our study, we investigated the biological role of TXNIP and its potential molecular mechanism in the human hepatic cell line (HL7702 cells). Using oxygen-glucose deprivation and reoxygenation (OGD/R) to create a cell model of hepatic I/R injury, we found that the mRNA and protein expression levels of TXNIP were upregulated in HL7702 cells exposed to OGD/R. TXNIP overexpression remarkably promoted OGD/R-induced cell apoptosis and lactate dehydrogenase (LDH) release, both of which were significantly decreased by TXNIP knockdown. The production of malondialdehyde (MDA) was also increased by TXNIP overexpression, but was reduced by TXNIP knockdown. Moreover, TXNIP overexpression significantly upregulated the phosphorylation of p38 and JNK, which was remarkably inhibited by TXNIP knockdown. Additionally, p38-specific inhibitor SB203580 abrogated the effect of TXNIP overexpression on OGD/R-induced cell injury. Taken together, these results indicated that TXNIP knockdown alleviated hepatocyte I/R injury through preventing p38/JNK pathway activation. Thus, TXNIP might offer a novel potential therapeutic target for the treatment of hepatic I/R injury.

High-accuracy measurement of the focal length and distortion of optical systems based on interferometry.

A figure measuring interferometer (FMI) method is proposed for high-accuracy measurement of the focal length and distortion of optical systems simultaneously. FMI uses the Zernike coefficients of interference fringe to identify the image point position precisely, and then measures the distance between the image points under the different fields to determine the image height. The field of view can also be accurately obtained by a precise rotating platform. Linear fitting between the field of view and the image height is used to calculate the focal length and distortion. The experimental results indicate that FMI has a relative expanded standard uncertainty of less than 0.01% for focal length and 0.02% for distortion. In brief, the proposed method is feasible for measurement of the focal length and distortion with high accuracy, promising further industrial applications.

Effects of dietary inclusion of Moringa oleifera leaves on growth and some systemic and mucosal immune parameters of seabream.

The effect of the dietary incorporation of drumstick, Moringa oleifera, leaf meal (MOL; 0, 5, 10 and 15%) on the growth, feed utilization, some skin mucus and systemic immune parameters and intestinal immune-related gene expression in gilthead seabream (Sparus aurata) specimens. The experiment lasted 4 weeks. The results revealed that MOL can be incorporated in S. aurata diet up to 10% with no significant negative effect on growth and feed utilization. However, there was a significant decrease with MOL at a level of 15% after 2 weeks of feeding. The systemic immune status of fish fed with the different levels of MOL showed an improvement in head kidney leucocyte phagocytosis, respiratory burst and peroxidase activities. Also, serum humoral components, including protease, ACH50 and lysozyme activities and IgM level, increased with MOL inclusion especially at the 5% level. MOL at 5% improved skin-mucosal immunity such as protease, antiprotease, peroxidase and lysozyme activities. Moreover, the feeding of MOL revealed an upregulation of the intestinal mucosal immunity genes (lyso and c3), tight junction proteins (occludin and zo-1) and anti-inflammatory cytokines (tgf-ß) with a downregulation of pro-inflammatory cytokine (tnf-α). Therefore, it is recommended to incorporate MOL in S. aurata diets at a level of 5% for the best immune status or 10% for the high growth performance and acceptable immune surveillance. Graphical abstract ᅟ.

Extended shift-rotation method for absolute interferometric testing of a spherical surface with pixel-level spatial resolution.

An improved shift-rotation method for the absolute testing of spherical surfaces is developed to obtain pixel-level spatial resolution and a low noise propagation ratio. The absolute testing process includes multiple rotational tests and two lateral shifting tests with large shifts. A wavefront reconstruction algorithm based on subaperture division and least squares fitting is proposed to reconstruct the surface figure of the test optics. Numerical simulation results show that the method reveals high-frequency figures missed in the traditional Zernike-based shift-rotation method. The algorithm error is lower than 0.4%, and the noise propagation ratio can be reduced by 70% using large shifts. The absolute testing of spherical optics is carried out to verify this method. One spherical surface was tested with the presented absolute testing method and the method using a point diffraction interferometer. The difference of the measurement results based on the two methods showed that the testing uncertainty reached 0.19 nm root mean square (RMS), which indicated that the presented method has potential subnanometer testing uncertainty.

Practical phase unwrapping of interferometric fringes based on unscented Kalman filter technique.

A phase unwrapping algorithm for interferometric fringes based on the unscented Kalman filter (UKF) technique is proposed. The algorithm can bring about accurate phase unwrapping and good noise suppression simultaneously by incorporating the true phase and its derivative in the state vector estimation through the UKF process. Simulations indicate that the proposed algorithm has better accuracy than some widely employed phase unwrapping approaches in the same noise condition. Also, the time consumption of the algorithm is reasonably acceptable. Applications of the algorithm in our different optical interferometer systems are provided to demonstrate its practicability with good performance. We hope this algorithm can be a practical approach that can help to reduce the systematic errors significantly induced by phase unwrapping process for interferometric measurements such as wavefront distortion testing, surface figure testing of optics, etc.

A novel modified peptide derived from membrane-proximal external region of human immunodeficiency virus type 1 envelope significantly enhances retrovirus infection.

Efficient gene transfer is a critical goal in retroviral transduction. Several peptides capable of forming amyloid fibrils, such as the 39-residue semen-derived infection-enhancing peptide (SEVI), have demonstrated the ability to boost retroviral gene delivery. Here, a 13-residue peptide P13 (Ac-(671) NWFDITNWLWYIK(683)) derived from the membrane-proximal external region of the human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane protein, together with its 16-residue peptide derivative (P16) were found to enhance HIV-1 infection significantly. Both peptides, P13 and P16, could form amyloid fibril structures to potently enhance HIV-1 infectivity. Further investigations showed that both aromatic Trp residues and cationic Lys residues contributed to the enhancement of HIV-1 infection by these two active peptides. P16 could more effectively augment HIV-1 YU-2 infection than SEVI, implying its potential applications as a tool in the lab to improve gene transfer rates.

Impact of the COVID-19 pandemic on routine vaccination coverage under varying prevalence Conditions: A cohort study in Beijing, China.

BACKGROUND: The COVID-19 pandemic has experienced various phases including outbreaks, a global health crisis, and eventual de-escalation from a public health emergency of international concern, significantly affecting the delivery and utilization of healthcare services. This study aimed to evaluate the impact of the COVID-19 pandemic on the coverage rate of routine immunization in children under varying prevalence conditions. METHODS: We conducted a retrospective, population-based cohort study in Beijing, China, utilizing stratified random sampling by birthdate to obtain a sample of 29,811 participants. Subjects were categorized into four cohorts based on when they became eligible for vaccination: the Pre-COVID Period cohort, the COVID-19 Low Epidemic Period cohort, the COVID-19 Surging Period cohort, and the COVID-19 Slowing Down Period cohort. A one-month follow-up was conducted. Cox proportional hazards model was employed to examine associations between the COVID-19 epidemic status and timely vaccination. RESULTS: Participants age-eligible for vaccination during the COVID-19 Low Epidemic Period demonstrated higher rates of timely vaccination (HR 1.18, 95% CI 1.15-1.22) compared to those eligible during the Pre-COVID Period. Conversely, those eligible during the COVID-19 Surging Period displayed lower rates (HR 0.73, 95% CI 0.66-0.82). No significant difference in vaccination timeliness was observed for those eligible during the COVID-19 Slowing Down Period in comparison to the Pre-COVID Period (HR 0.99, 95% CI 0.91-1.09). By the end of May 2023, DTP3 rate among eligible children during the COVID-19 Surging Period had surpassed 90%. CONCLUSIONS: Significantly declining rates of timely vaccination were observed during the COVID-19 Surging Period, which lasted two months, but not during the nearly three-year-long COVID-19 Low Epidemic Period. An upward trend in vaccination timeliness followed, culminating in a return to baseline levels over the subsequent 3-4 months. Our findings suggested that the pandemic exerted a decreasing and recoverable impact on the coverage rate of routine immunizations in China.

Carbon-reinforced Ni3S2/Ti3C2Tx MXene composite as an anode for superior-performance lithium-ion capacitors.

Lithium ion capacitors (LICs) are a new generation of energy storage devices that combine the super energy storage capability of lithium ion batteries with the satisfactory power density of supercapacitors. The development of high-performance LICs still faces great challenges due to the unbalanced reaction kinetics at the anode and cathode. Therefore, it is an inevitable need to enhance the electron/ion transfer capability of the anode materials. In this paper, to obtain a superior-rate and high-capacity Ni3S2-based anode, highly conductive Ti3C2Tx MXene sheets were introduced to sever as the carrier of Ni3S2 nanoparticles and simultaneously an amorphous carbon layer which coats onto the surface of Ni3S2 nanoparticles was in-situ generated by the carbonization of dopamine reactant. The as-synthesized Ni3S2/Ti3C2Tx/C composite exhibits a high specific surface area (112.6 m2/g) because of the addition of Ti3C2Tx that can reduce the aggregation of Ni3S2 nanoparticles and the in-situ generated amorphous carbon layer that can suppress the growth of Ni3S2 nanoparticles. The Ni3S2/Ti3C2Tx/C anode possesses a remarkable reversible discharge specific capacity (626.0 mAh/g under 0.2 A/g current density), which increases to 1150.8 mAh/g after 400-cycle charge/discharge measurement at the same measurement condition indicating eminent cyclability, along with superior rate capability. To construct a superior-performance LIC device, a sterculiae lychnophorae derived porous carbon (SLPC) cathode with an average discharge specific capacity of 73.4 mAh/g@0.1A/g was prepared. The Ni3S2/Ti3C2Tx/C//SLPC LIC device with optimal cathode/anode mass ratio has a satisfactory energy density ranging from 32.8 to 119.1 Wh kg-1 at the corresponding power density of 8799.4 to 157.5 W kg-1, together with a prominent capacity retention (95.5 %@1 A/g after 10,000 cycles).

Carvedilol to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by liver stiffness: study protocol for a randomied, double-blind, placebo-controlled, multicentre trial in China.

INTRODUCTION: Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy. METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073864.

Safety and effectiveness of a 2009 H1N1 vaccine in Beijing.

BACKGROUND: After the first monovalent 2009 pandemic influenza A (H1N1) vaccine became available in September 2009, Chinese officials conducted a mass vaccination program in Beijing. We evaluated the safety and effectiveness of the vaccine. METHODS: During a 5-day period in September 2009, a total of 95,244 children and adults received the PANFLU.1 vaccine (Sinovac Biotech), a monovalent split-virion vaccine of 15 µg of hemagglutinin antigen without adjuvant. We assessed adverse events after immunization through an enhanced passive-surveillance system and through active surveillance, using diary cards and telephone interviews. Active surveillance for neurologic diseases was implemented in hospitals citywide. To assess vaccine effectiveness, we compared the rates of reported laboratory-confirmed cases of 2009 H1N1 virus infection in students who received the vaccine with the rates in those who did not receive the vaccine, starting 2 weeks after the mass vaccination. RESULTS: As of December 31, 2009, adverse events were reported by 193 vaccine recipients. Through hospital-based active surveillance, 362 cases of incident neurologic diseases were identified within 10 weeks after the mass vaccination, including 27 cases of the Guillain-Barré syndrome. None of the neurologic conditions occurred among vaccine recipients. From 245 schools, 25,037 students participated in the mass vaccination and 244,091 did not. During the period from October 9 through November 15, 2009, the incidence of confirmed cases of 2009 H1N1 virus infection per 100,000 students was 35.9 (9 of 25,037) among vaccinated students and 281.4 (687 of 244,091) among unvaccinated students. Thus, the estimated vaccine effectiveness was 87.3% (95% confidence interval, 75.4 to 93.4). CONCLUSIONS: Among 95,244 children and adults in Beijing, the PANFLU.1 vaccine had a safety profile similar to those of seasonal influenza vaccines and appeared to be effective against confirmed H1N1 virus infection in school-age children. (Funded by the Beijing Municipal Health Bureau.).

Multiple antigen peptide mimetics containing gp41 membrane-proximal external region elicit broad neutralizing antibodies against human immunodeficiency virus type 1 in guinea pigs.

Eliciting a broadly neutralizing antibody response against the HIV-1 membrane-proximal external region (MPER) mimicking the activity of 4E10 and 2F5 monoclonal antibodies remains a major challenge. In this study, two novel tetra-branched peptide immunogens, 4E10- and 2F5-MAP4, were designed and synthesized using a MAP system. Guinea pigs were immunized with either of these two synthetic immunogens emulsified in an oil-phase adjuvant at 3-week intervals. After four immunizations, epitope-specific antibody responses were induced successfully, and moderate neutralizing activities against tier 1 (clades B, BC, AE) and tier 2 (clade C) HIV-1 pseudoviruses were detectable in unfractionated sera and purified IgGs. The synthetic gp41 membrane-proximal external region peptide mimetics, 4E10- and 2F5-MAP4, assisted by an appropriate adjuvant, are promising prophylactic vaccine candidates potentially capable of eliciting broadly neutralizing antibody responses against HIV-1.

Vaccination coverage survey of children aged 1-3 years in Beijing, China, 2005-2021.

BACKGROUND: The routine immunization program for children is a primary strategy and a core part of vaccination. Achieving and maintaining high level of vaccination coverage are important to reduce morbidity and mortality caused by vaccine-preventable diseases. In Beijing, annual coverage surveys have been conducted since 2005. It is necessary and possible to assess the level and trend of routine vaccination coverage of children in Beijing as well as the disruption of coronavirus disease 2019 (COVID-19) pandemic and provide the reference for the further improve the vaccination coverage. METHODS: The data of 61,521 children aged 1-3 years in the vaccination coverage surveys during 2005-2021 were analyzed by Beijing Center for Disease Control and Prevention. Descriptive epidemiological method was used to analyze the data and the difference of vaccination coverage within the time period. RESULTS: More than 99 % of participants had immunization cards and electronic immunization records. The concordance rate of both records were also over 99 %. During 2011-2019, the rates of on-time and in-time vaccination of each routine vaccine reached 96 % or more and increased significantly (all P values <0.05), compared with that of 2005-2010. All rates of the investigated vaccine, except for Bacillus Calmette-Guérin vaccine (BCG) and the first dose of hepatitis B vaccine (HepB), decreased in 2020-2021 significantly (all P values <0.05). For the causes of failing to vaccinate on time, delayed vaccination accounted for 47.82 %. The top two vaccines to be missed were the first dose of hepatitis A vaccine and the 4th dose of diphtheria-tetanus-acellular pertussis vaccine, accounting for 21.41 % and 20.79 %, respectively. The main reason for zero-dose/drop-out vaccination was "Guardians regarded the immunization service time as inappropriate", accounting for 72.27 %. CONCLUSION: The coverage level and service quality of routine immunization in Beijing were relatively high. However, as influenced by COVID-19 epidemics, both on-time and in-time vaccination rates decreased significantly, except for BCG and HepB. Under the background of COVID-19 pandemic, the keys to maintain high level of vaccination coverage include flexible immunization service time to ensure the guardians bringing their children for vaccination timely, and more attention from providers to the doses after children's first birthday.