Characterization of genital chlamydia trachomatis infection among women attending infertility and gynecology clinics in Hunan, China.

BACKGROUND: Genital infection with Chlamydia trachomatis (C. trachomatis) is a major public health issue worldwide. It can lead to cervicitis, urethritis, and infertility. This study was conducted to determine the characteristics of genital C. trachomatis infection among women attending to the infertility and gynecology clinics. METHODS: Endocervical swabs were collected from 8,221 women for C. trachomatis nucleotide screening and genotyping, while serum samples were collected for C. trachomatis pgp3 antibody determination using luciferase immunosorbent assays. RESULTS: High C. trachomatis DNA prevalence (3.76%) and seroprevalence (47.46%) rates were found, with genotype E (27.5%) being the most prevalent. C. trachomatis omp1 sense mutation was associated with cervical intraepithelial neoplasia (CIN) (odds ratio [OR] = 6.033, 95% confidence interval [CI] = 1.219-39.185, p = 0.045). No significant differences in C. trachomatis seroprevalence rates were observed between women with detectable C. trachomatis DNA in the infertility and routine physical examination groups (86.67% vs. 95%, p > 0.05); however, among women with negative C. trachomatis DNA, the former group had a markedly higher seroprevalence than the latter group (56.74% vs. 20.17%, p < 0.001). C. trachomatis DNA, but not pgp3 antibody, was significantly associated with CIN (OR = 4.087, 95% CI = 2.284-7.315, p < 0.001). CONCLUSION: Our results revealed a high prevalence, particularly seroprevalence, of C. trachomatis among women with infertility. Furthermore, we found an association between C. trachomatis omp1 sense mutations and CIN. Therefore, C. trachomatis serves as a risk factor for CIN.

Evaluating the Clinical Utility of Semi-Quantitative Luciferase Immunosorbent Assay Using Treponema pallidum Antigens in Syphilis Diagnosis and Treatment Monitoring.

OBJECTIVE: To assess the clinical applicability of a semi-quantitative luciferase immunosorbent assay (LISA) for detecting antibodies against Treponema pallidum antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) in diagnosing and monitoring syphilis. METHOD: LISA for detection of anti-TP15, TP17, and TP47 antibodies was developed and evaluated for syphilis diagnosis using 261 serum samples (161 syphilis, 100 non-syphilis). 90 serial serum samples from six syphilis rabbit models (three treated, three untreated) and 110 paired serum samples from 55 syphilis patients were used to assess treatment effects by utilizing TRUST as reference. RESULTS: Compared to TPPA, LISA-TP15, LISA-TP17, and LISA-TP47 showed sensitivity of 91.9%, 96.9%, and 98.8%, specificity of 99%, 99%, and 98%, and AUC of 0.971, 0.992, and 0.995, respectively, in diagnosing syphilis. Strong correlations (rs = 0.89-0.93) with TPPA were observed. In serial serum samples from rabbit models, significant difference in the relative light unit (RLU) were observed between the treatment and control group for LISA-TP17 (days 31-51) and LISA-TP47 (days 41). In paired serum samples form syphilis patients, TRUST titers and the RLU of LISA-TP15, LISA-TP17, and LISA-TP47 decreased post treatment (P < 0.001). When TRUST titers decreased by 0, 2, 4, or ≥8-folds, the RLU decreased by 17.53%, 31.34%, 48.62%, and 72.79% for LISA-TP15; 8.84%, 17.00%, 28.37%, and 50.57% for LISA-TP17; 22.25%, 29.79%, 51.75%, and 70.28% for LISA-TP47, respectively. CONCLUSION: Semi-quantitative LISA performs well for syphilis diagnosis while LISA-TP17 is more effective for monitoring syphilis treatment in rabbit models and clinical patients.

The serodiagnositic value of Chlamydia trachomatis antigens in antibody detection using luciferase immunosorbent assay.

Introduction: Among the different antigens used in the detection of anti-Chlamydia trachomatis antibodies, significant differences in sensitivity and specificity have been observed. Further evaluation of C. trachomatis antigens in antibody detection is urgently needed for the development and application of C. trachomatis serologic assays. Methods: Chlamydia trachomatis antigens Pgp3, TmeA, InaC, and HSP60 were selected and used in luciferase immunosorbent assay (LISA). The detection results obtained from well-defined C. trachomatis positive and negative samples were compared with the commercial C. trachomatis ELISA (Mikrogen) for performance evaluation. Results: Pgp3, TmeA, InaC, and HSP60-based LISA showed sensitivity of 92.8, 88.8, 90.4, and 94.4%, and specificity of 99.2, 99.2, 99.2, and 92%, respectively. ROC analysis indicated that Pgp3-based LISA showed similar performance to Mikrogen ELISA (AUC 0.986 vs. 0.993, p = 0.207). Furthermore, four C. trachomatis antigens achieved strong diagnostic efficiency, i.e., positive likelihood ratios [+LR] ≥ 10 in C. trachomatis-infected women and negative likelihood ratios [-LR] ≤ 0.1 in C. trachomatis negative low exposure risk children, but only Pgp3 and TmeA showed strong diagnostic value in general adults. In addition, Pgp3, TmeA, and InaC, but not HSP60, achieved high performance, i.e., both positive predictive value (PPV) and negative predictive value (NPV) ≥ 90.9%, and showed no significant cross-reactivity with anti-Chlamydiapneumoniae. Conclusion: Three C. trachomatis species-specific antigens Pgp3, TmeA, and InaC show superior performance in the detection of anti-C. trachomatis antibody, indicating the potential to be used in developing C. trachomatis serologic tests.

Establishment and application of a rapid assay for GII.4/GII.17 NoV detection based on the combination of CRISPR/Cas13a and isothermal amplification.

Introduction: Norovirus (NoV) is one of the most important agents responsible for viral acute gastroenteritis, among which GII.4 NoV is the predominant strain worldwide, and GII.17 NoV surpassed GII.4 in some epidemic seasons. Rapid and accurate gene recognition is essential for a timely response to NoV outbreaks. Methods: In the present study, the highly conserved regions of GII.4 and GII.17 NoVs were identified in the junction of open reading frame (ORF) 1 and ORF2 and then amplified by isothermal recombinase-aided amplification (RAA), followed by the cleavage of CRISPR-Cas13a with screened CRISPR RNAs (crRNAs) and RAA primers. The entire detection procedure could be completed within 40 min using a thermostat, and the results could be read out by the naked eye under a portable blue light transilluminator. Discussion: The assay showed a high sensitivity of 97.96% and a high specificity of 100.0%. It offered a low limit of detection (LOD) of 2.5×100 copies/reaction and a coincidence rate of 96.75% in 71 clinical fecal samples. Overall, rapid and inexpensive detection of GII.4/GII.17 NoVs was established, which makes it possible to be used in areas with limited resources, particularly in low-income countries. Furthermore, it will contribute to assessing transmission risks and implementing control measures for GII.4/GII.17 NoVs, making healthcare more accessible worldwide.

A photocontrolled one-pot isothermal amplification and CRISPR-Cas12a assay for rapid detection of SARS-CoV-2 Omicron variants.

CRISPR-Cas technology has widely been applied to detect single-nucleotide mutation and is considered as the next generation of molecular diagnostics. We previously reported the combination of nucleic acid amplification (NAA) and CRISPR-Cas12a system to distinguish major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, the mixture of NAA and CRISPR-Cas12a reagents in one tube could interfere with the efficiency of NAA and CRISPR-Cas12a cleavage, which in turn affects the detection sensitivity. In the current study, we employed a novel photoactivated CRISPR-Cas12a strategy integrated with recombinase polymerase amplification (RPA) to develop one-pot RPA/CRISPR-Cas12a genotyping assay for detecting SARS-CoV-2 Omicron sub-lineages. The new system overcomes the potential inhibition of RPA due to early CRISPR-Cas12a activation and cleavage of the target template in traditional one-pot assay using photocleavable p-RNA, a complementary single-stranded RNA to specifically bind crRNA and precisely block Cas12a activation. The detection can be finished in one tube at 39℃ within 1 h and exhibits a low limit of detection of 30 copies per reaction. Our results demonstrated that the photocontrolled one-pot RPA/CRISPR-Cas12a assay could effectively identify three signature mutations in the spike gene of SARS-CoV-2 Omicron variant, namely, R346T, F486V, and 49X, and distinguish Omicron BA.1, BA.5.2, and BF.7 sub-lineages. Furthermore, the assay achieved a sensitivity of 97.3% and a specificity of 100.0% and showed a concordance of 98.3% with Sanger sequencing results.IMPORTANCEWe successfully developed one-pot recombinase polymerase amplification/CRISPR-Cas12a genotyping assay by adapting photocontrolled CRISPR-Cas technology to optimize the conditions of nucleic acid amplification and CRISPR-Cas12a-mediated detection. This innovative approach was able to quickly distinguish severe acute respiratory syndrome coronavirus 2 Omicron variants and can be readily modified for detecting any nucleic acid mutations. The assay system demonstrates excellent clinical performance, including rapid detection, user-friendly operations, and minimized risk of contamination, which highlights its promising potential as a point-of-care testing for wide applications in resource-limiting settings.

Effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 Omicron BA.2 infection in Guangdong, China: a cohort study.

The effectiveness of COVID-19 vaccines wanes over time and the emergence of the SARS-CoV-2 Omicron variant led to the accelerated expansion of efforts for booster vaccination. However, the effect and contribution of booster vaccination with inactivated COVID-19 vaccines remain to be evaluated. We conducted a retrospective close contacts cohort study to analyze the epidemiological characteristics and Omicron infection risk, and to evaluate the effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection, symptomatic COVID-19, and COVID-19 pneumonia during the outbreaks of Omicron BA.2 infection from 1 February to 31 July 2022 in Guangdong, China. A total of 46,547 close contacts were identified while 6.3% contracted Omicron BA.2 infection, 1.8% were asymptomatic infection, 4.1% developed mild COVID-19, and 0.3% had COVID-19 pneumonia. We found that females and individuals aged 0-17 or ≥ 60 years old were more prone to SARS-CoV-2 infection. The vaccinated individuals showed lower infection risk when compared with the unvaccinated people. The effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 was 28.6% (95% CI: 11.6%, 35.0%) and 39.6% (95% CI: 30.0, 47.9) among adults aged ≥ 18 years old, respectively when compared with full vaccination. Booster vaccination provided a moderate level of protection against SARS-CoV-2 infection (VE: 49.9%, 95% CI: 22.3%-67.7%) and symptomatic COVID-19 (VE: 62.6%, 95% CI: 36.2%-78.0%) among adults aged ≥ 60 years old. Moreover, the effectiveness of booster vaccination was 52.2% (95% CI: 21.3%, 70.9%) and 83.8% (95% CI: 28.1%, 96.3%) against COVID-19 pneumonia in adults aged ≥ 18 and ≥ 60 years old, respectively. The reduction of absolute risk rate of COVID-19 pneumonia in the booster vaccination group was 0·96% (95% CI: 0.33%, 1.11%), and the number needed to vaccinate to prevent one case of COVID-19 pneumonia was 104 (95% CI: 91, 303) in adults aged ≥ 60 years old. In summary, booster vaccination with inactivated COVID-19 vaccines provides a low level of protection against infection and symptomatic in adults of 18-59 years old, and a moderate level of protection in older adults of more than 60 years old, but a high level of protection against COVID-19 pneumonia in older adults.

SARS-CoV-2 incidence, seroprevalence, and COVID-19 vaccination coverage in the homeless population: a systematic review and meta-analysis.

Objectives: SARS-CoV-2 infection and COVID-19 vaccination of homeless people are a serious public health concern during COVID-19 pandemic. We aimed to systematically assess SARS-CoV-2 incidence, seroprevalence, and COVID-19 vaccination coverage in homeless people, which are important to inform resource allocation and policy adjustment for the prevention and control of COVID-19. Methods: We searched PubMed, Web of Science, and the World Health Organization COVID-19 database for the studies of SARS-CoV-2 incidence, seroprevalence, and COVID-19 vaccination coverage in the homeless population. Subgroup analyses were conducted to pool SARS-CoV-2 incidence and seroprevalence in sheltered homeless, unsheltered homeless, and mixed population, respectively. Potential sources of heterogeneity in the estimates were explored by meta-regression analysis. Results: Forty-nine eligible studies with a total of 75,402 homeless individuals and 5,000 shelter staff were included in the meta-analysis. The pooled incidence of SARS-CoV-2 infection was 10% (95% CI: 7 to 12%) in the homeless population and 8% (5 to 12%) for shelter staff. In addition, the overall estimated SARS-CoV-2 specific seroprevalence was 19% (8 to 33%) for homeless populations and 22% (3 to 52%) for shelter staff, respectively. Moreover, for the homeless subjects, the pooled incidence was 10% (4 to 23%) for asymptomatic SARS-CoV-2 infections, 6% (1 to 12%) for symptomatic SARS-CoV-2 infections, 3% (1 to 4%) for hospitalization for COVID-19, and 1% (0 to 2%) for severe COVID-19 cases, respectively while no COVID-19-related death was reported. Furthermore, the data derived from 12 included studies involving 225,448 homeless individuals revealed that the pooled proportion of one dose COVID-19 vaccination was 41% (35 to 47%), which was significantly lower than those in the general population. Conclusion: Our study results indicate that the homeless people remain highly susceptible to SARS-CoV-2 infection, but COVID-19 vaccination coverage was lower than the general population, underscoring the need for prioritizing vaccine deployment and implementing enhanced preventive measures targeting this vulnerable group.

Surface-Enhanced Raman Scattering Active Core-Shell Ag NPs@Carbon Dots with Enzyme-Mimicking Activities for Label-Free Measurement Cholesterol.

Serological-sensitive testing of cholesterol holds significant value in the fields of healthcare and clinical diagnosis. This study reports on the preparation of peroxidase-mimicking nanozymes through the wrapping of N, S-doped carbon dots (DCDs) on the surface of silver nanoparticles (Ag NPs@DCD). The shell-core structure of Ag NPs@DCD displays peroxidase-mimicking capability, with the potential to catalyze inactive Raman probe molecules into the Raman reporters. Furthermore, a "shell-isolated nanoparticles-enhanced Raman spectroscopy" structure exhibited an enhanced Raman signal of reporter molecules. Ag NPs@DCD were utilized to create a label-free SERS sensing system for high-performance detection of cholesterol in serum samples. These results demonstrate the potential of the novel nanozyme-based SERS approach for clinical diagnosis.

Development and evaluation of a new luciferase immunosorbent assay to detect GII.6 norovirus-specific IgG in different domestic and wild animals.

Noroviruses (NoVs) are the leading viral pathogens globally causing acute gastroenteritis (AGE) in humans, posing a significant global health threat and economic burden. Recent investigations revealed that human NoVs had been detected in different animals, which raises concerns about whether NoVs are potential zoonotic diseases. This study developed a novel luciferase immunosorbent assay (LISA) to detect GII.6 NoV IgG based on P protein of VP1. The LISA showed high specificity (99.20%) and sensitivity (92.00%) with 4-16 times more sensitivity compared with an ELISA. NoV-LISA was reproducible with human serum regarding the inter- and intra-assay coefficient of variance values. Potential cross-reactivity was also evaluated using mice serum immunized by other antigens, which showed that NoV-LISA could differentiate GII.6 NoV from rotavirus and various genotypes of NoV. Specific GII.6 NoV IgG was widely detected in different domestic and wild animals, including dogs, pigs, bats, rats, and home shrews, with various IgG-positive rates ranging from 2.5 to 74.4%. In conclusion, our newly developed NoV-LISA assay is suitable for NoV-specific IgG detection in humans and animals. The wide distribution of IgG antibodies against human NoV indicates potential zoonotic transmission between humans and animals.

The impact of pre-existing influenza antibodies and inflammatory status on the influenza vaccine responses in older adults.

Age-associated immune changes and pre-existing influenza immunity are hypothesized to reduce influenza vaccine effectiveness in older adults, although the contribution of each factor is unknown. Here, we constructed influenza-specific IgG landscapes and determined baseline concentrations of cytokines typically associated with chronic inflammation in older adults (TNF-α, IL-10, IL-6, and IFN-γ) in 30 high and 29 low influenza vaccine responders (HR and LR, respectively). In a background of high H3 antibody titers, vaccine-specific H3, but not H1, antibody titers were boosted in LRs to titers comparable to HRs. Pre-vaccination concentrations of IL-10 were higher in LRs compared with HRs and inversely correlated with titers of pre-existing influenza antibodies. Baseline TNF-α concentrations were positively correlated with fold-increases in antibody titers in HRs. Our findings indicate that baseline inflammatory status is an important determinant for generating post-vaccination hemagglutinin-inhibition antibodies in older adults, and IgG responses can be boosted in the context of high pre-existing immunity.

A Schematic Colorimetric Assay for Sialic Acid Assay Based on PEG-Mediated Interparticle Crosslinking Aggregation of Gold Nanoparticles.

Sialic acid (SA) is a well-known component of glycoproteins, which have applications in various functional processes on the cell's surface. The colorimetric is a simpler and more convenient method for measuring SA due to its low-cost apparatus and visual signal changes. This work focused on the unpredictable interparticle crosslinking aggregation of the functionalized gold nanoparticles (AuNPs) in complex media. We proposed a balance of the Derjaguin-Landau-Verwey-Overbeek (DLVO)-type aggregation and molecule-based interaction method to solve this problem. Here, we report a novel colorimetric assay for the determination of SA using 4-mercaptophenyl boronic acid (4-MPBA) as an analyte's recognition molecule, and negative charge PEG400 was used to repulsive the interparticle crosslinking. The proposed sensing platform shows a linear relationship between the ratio of the absorbance intensity (A525/A660) and concentration of SA from 0.05 to 8 mM (R2 = 0.997) and a detection limit of 48 µM was observed. The novel gold-based colorimetric sensor is easy to fabricate, reproducible in its test performance and has been successfully applied for the detection of SA in biological and healthcare product samples.

Transmission characteristics and inactivated vaccine effectiveness against transmission of the SARS-CoV-2 Omicron BA.2 variant in Shenzhen, China.

We conducted a retrospective cohort study to evaluate the transmission risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 variant and the effectiveness of inactivated COVID-19 vaccine boosters in Shenzhen during a BA.2 outbreak period from 1 February to 21 April 2022. A total of 1,248 individuals were infected with the BA.2 variant, and 7,855 close contacts were carefully investigated. The risk factors for the high secondary attack rate of SARS-CoV-2 infection were household contacts [adjusted odds ratio (aOR): 1.748; 95% confidence interval (CI): 1.448, 2.110], younger individuals aged 0-17 years (aOR: 2.730; 95% CI: 2.118, 3.518), older persons aged ≥60 years (aOR: 1.342; 95% CI: 1.135, 1.588), women (aOR: 1.442; 95% CI: 1.210, 1.718), and the subjects exposed to the post-onset index cases (aOR: 8.546; 95% CI: 6.610, 11.050), respectively. Compared with the unvaccinated and partially vaccinated individuals, a relatively low risk of secondary attack was found for the individuals who received booster vaccination (aOR: 0.871; 95% CI: 0.761, 0.997). Moreover, a high transmission risk was found for the index cases aged ≥60 years (aOR: 1.359; 95% CI: 1.132, 1.632), whereas a relatively low transmission risk was observed for the index cases who received full vaccination (aOR: 0.642; 95% CI: 0.490, 0.841) and booster vaccination (aOR: 0.676; 95% CI: 0.594, 0.770). Compared with full vaccination, booster vaccination of inactivated COVID-19 vaccine showed an effectiveness of 24.0% (95% CI: 7.0%, 37.9%) against BA.2 transmission for the adults ≥18 years and 93.7% (95% CI: 72.4%, 98.6%) for the adults ≥60 years, whereas the effectiveness was 51.0% (95% CI: 21.9%, 69.3%) for the individuals of 14 days to 179 days after booster vaccination and 51.2% (95% CI: 37.5%, 61.9%) for the non-household contacts. The estimated mean values of the generation interval, serial interval, incubation period, latent period, and viral shedding period were 2.7 days, 3.2 days, 2.4 days, 2.1 days, and 17.9 days, respectively. In summary, our results confirmed that the main transmission route of Omicron BA.2 subvariant was household contact, and booster vaccination of the inactivated vaccines was relatively effective against BA.2 subvariant transmission in older people.

Evaluation of antiretroviral therapy effect and prognosis between HIV-1 recent and long-term infection based on a rapid recent infection testing algorithm.

Early diagnosis of HIV-1 infection and immediate initiation of combination antiretroviral therapy (cART) are important for achieving better virological suppression and quicker immune reconstitution. However, no serological HIV-1 recency testing assay has been approved for clinical use, and the real-world clinical outcomes remain to be explored for the subjects with HIV-1 recent infection (RI) or long-term infection (LI) when antiretroviral therapy is initiated. In this study, a HIV-1 rapid recent-infection testing strip (RRITS) was developed and incorporated into the recent infection testing algorithms (RITAs) to distinguish HIV-1 RI and LI and to assess their clinical outcomes including virological response, the recovery of CD4+ T-cell count and CD4/CD8 ratio and the probability of survival. We found that the concordance between our RRITS and the commercially available LAg-Avidity EIA was 97.13% and 90.63% when detecting the longitudinal and cross-sectional HIV-1 positive samples, respectively. Among the 200 HIV-1 patients analyzed, 22.5% (45/200) of them were RI patients and 77.5% (155/200) were chronically infected and 30% (60/200) of them were AIDS patients. After cART, 4.1% (5/155) of the LI patients showed virological rebound, but none in the RI group. The proportion of CD4+ T-cell count >500 cells/mm3 was significantly higher in RI patients than in LI after 2 years of cART with a hazard ratio (HR) of 2.6 (95% CI: 1.9, 3.6, p < 0.0001) while the probability of CD4/CD8 = 1 was higher in RI than in LI group with a HR of 3.6 (95% CI: 2.2, 5.7, p < 0.0001). Furthermore, the immunological recovery speed was 16 cells/mm3/month for CD4+ T-cell and 0.043/month for the ratio of CD4/CD8 in the RI group, and was bigger in the RI group than in the LI patients (p < 0.05) during the 1st year of cART. The survival probability for LI patients was significantly lower than that for RI patients (p < 0.001). Our results indicated that RRITS combined with RITAs could successfully distinguish HIV-1 RI and LI patients whose clinical outcomes were significantly different after cART. The rapid HIV-1 recency test provides a feasible assay for diagnosing HIV-1 recent infection and a useful tool for predicting the outcomes of HIV-1 patients.

Identification and characterization of mixed infections of Chlamydia trachomatis via high-throughput sequencing.

Precise genotyping is necessary to understand epidemiology and clinical manifestations of Chlamydia trachomatis infection with different genotypes. Next-generation high-throughput sequencing (NGHTS) has opened new frontiers in microbial genotyping, but has been clinically characterized in only a few settings. This study aimed to determine C. trachomatis genotypes in particular mixed-genotype infections and their association with clinical manifestations and to characterize the sensitivity and accuracy of NGHTS. Cervical specimens were collected from 8,087 subjects from physical examination center (PEC), assisted reproductive technology center (ART) and gynecology clinics (GC) of Chenzhou Hospital of China. The overall prevalence of C. trachomatis was 3.8% (311/8087) whereas a prevalence of 2.8, 3.7 and 4.8% was found in PEC, ART and GC, respectively. The most frequent three C. trachomatis genotypes were E (27.4%, 83/303), F (21.5%, 65/303) and J (18.2%, 55/303). Moreover, NGHTS identified 20 (6.6%, 20/303) mixed-genotype infections of C. trachomatis. Genotype G was more often observed in the subjects with pelvic inflammatory disease than genotype E (adjusted OR = 3.61, 95%CI, 1.02-12.8, p = 0.046). Mixed-genotype infection was associated with severe vaginal cleanliness (degree IV) with an adjusted OR of 5.17 (95%CI 1.03-25.9, p = 0.046) whereas mixed-genotype infection with large proportion of minor genotypes was associated with cervical squamous intraepithelial lesion (SIL) with an adjusted OR of 5.51 (95%CI 1.17-26.01, p = 0.031). Our results indicated that NGHTS is a feasible tool to identity C. trachomatis mixed-genotype infections, which may be associated with worse vaginal cleanliness and cervical SIL.

Efficient production of the ß-ionone aroma compound from organic waste hydrolysates using an engineered Yarrowia lipolytica strain.

This study demonstrates the feasibility of establishing a natural compound supply chain in a biorefinery. The process starts with the biological or chemical hydrolysis of food and agricultural waste into simple and fermentative sugars, followed by their fermentation into more complex molecules. The yeast strain, Yarrowia lipolytica, was modified by introducing high membrane affinity variants of the carotenoid cleavage dioxygenase enzyme, PhCCD1, to increase the production of the aroma compound, ß-ionone. The initial hydrolysis process converted food waste or sugarcane bagasse into nutrient-rich hydrolysates containing 78.4 g/L glucose and 8.3 g/L fructose, or 34.7 g/L glucose and 20.1 g/L xylose, respectively. During the next step, engineered Y. lipolytica strains were used to produce ß-ionone from these feedstocks. The yeast strain YLBI3120, carrying a modified PhCCD1 gene was able to produce 4 g/L of ß-ionone with a productivity of 13.9 mg/L/h from food waste hydrolysate. This is the highest yield reported for the fermentation of this compound to date. The integrated process described in this study could be scaled up to achieve economical large-scale conversion of inedible food and agricultural waste into valuable aroma compounds for a wide range of potential applications.

Development of fluorescent lateral flow immunoassay for SARS-CoV-2-specific IgM and IgG based on aggregation-induced emission carbon dots.

Understanding the dynamic changes in antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for evaluating the effectiveness of the vaccine and the stage for the recovery of the COVID-19 disease. A rapid and accurate method for the detection of SARS-CoV-2-specific antibodies is still urgently needed. Here, we developed a novel fluorescent lateral flow immunoassay (LFA) platform for the detection of SARS-CoV-2-specific IgM and IgG by the aggregation-induced emission carbon dots conjugated with the SARS-CoV-2 spike protein (SSP). The aggregation-induced emission carbon dots (AIE-CDs) are one of the best prospect fluorescent probe materials for exhibiting high emission efficiency in both aggregate and solid states. The AIE-CDs were synthesized and displayed dual fluorescence emission, which provides a new perspective for the design of a high sensitivity testing system. In this work, the novel LFA platform adopted the AIE carbon dots, which are used to detect SARS-CoV-2-specific IgM and IgG conveniently. Furthermore, this sensor had a low LOD of 100 pg/ml. Therefore, this newly developed strategy has potential applications in the areas of public health for the advancement of clinical research.

Epidemiological Characteristics and the Dynamic Transmission Model of Dengue Fever in Zhanjiang City, Guangdong Province in 2018.

Background: With the progress of urbanization, the mobility of people has gradually increased, which has led to the further spread of dengue fever. This study evaluated the transmissibility of dengue fever within districts and between different districts in Zhanjiang City to provide corresponding advice for cross-regional prevention and control. Methods: A mathematical model of transmission dynamics was developed to explore the transmissibility of the disease and to compare that between different regions. Results: A total of 467 DF cases (6.38 per 100,000 people) were reported in Zhanjiang City in 2018. In the model, without any intervention, the number of simulated cases in this epidemic reached about 950. The dengue fever transmissions between districts varied within and between regions. When the spread of dengue fever from Chikan Districts to other districts was cut off, the number of cases in other districts dropped significantly or even to zero. When the density of mosquitoes in Xiashan District was controlled, the dengue fever epidemic in Xiashan District was found to be significantly alleviated. Conclusions: When there is a dengue outbreak, timely measures can effectively control it from developing into an epidemic. Different prevention and control measures in different districts could efficiently reduce the risk of disease transmission.

A comprehensive analysis of the efficacy and effectiveness of COVID-19 vaccines.

It is urgently needed to update the comprehensive analysis about the efficacy or effectiveness of COVID-19 vaccines especially during the COVID-19 pandemic caused by SARS-CoV-2 Delta and Omicron variants. In general, the current COVID-19 vaccines showed a cumulative efficacy of 66.4%, 79.7%, and 93.6% to prevent SARS-CoV-2 infection, symptomatic COVID-19, and severe COVID-19, respectively, but could not prevent the asymptomatic infection of SARS-CoV-2. Furthermore, the current COVID-19 vaccines could effectively prevent COVID-19 caused by the Delta variant although the incidence of breakthrough infection of the SARS-CoV-2 Delta variant increased when the intervals post full vaccination extended, suggesting the waning effectiveness of COVID-19 vaccines. In addition, one-dose booster immunization showed an effectiveness of 74.5% to prevent COVID-19 caused by the Delta variant. However, current COVID-19 vaccines could not prevent the infection of Omicron sub-lineage BA.1.1.529 and had about 50% effectiveness to prevent COVID-19 caused by Omicron sub-lineage BA.1.1.529. Furthermore, the effectiveness was 87.6% and 90.1% to prevent severe COVID-19 and COVID-19-related death caused by Omicron sub-lineage BA.2, respectively, while one-dose booster immunization could enhance the effectiveness of COVID-19 vaccines to prevent the infection and COVID-19 caused by Omicron sub-lineage BA.1.1.529 and sub-lineage BA.2. Two-dose booster immunization showed an increased effectiveness of 81.8% against severe COVID-19 caused by the Omicron sub-lineage BA.1.1.529 variant compared with one-dose booster immunization. The effectiveness of the booster immunization with RNA-based vaccine BNT162b2 or mRNA-1273 was over 75% against severe COVID-19 more than 17 weeks after booster immunization whereas the heterogenous booster immunization showed better effectiveness than homologous booster immunization. In summary, the current COVID-19 vaccines could effectively protect COVID-19 caused by Delta and Omicron variants but was less effective against Omicron variant infection. One-dose booster immunization could enhance protection capability, and two-dose booster immunization could provide additional protection against severe COVID-19.

The Second Human Pegivirus, a Non-Pathogenic RNA Virus with Low Prevalence and Minimal Genetic Diversity.

The second human pegivirus (HPgV-2) is a virus discovered in the plasma of a hepatitis C virus (HCV)-infected patient in 2015 belonging to the pegiviruses of the family Flaviviridae. HPgV-2 has been proved to be epidemiologically associated with and structurally similar to HCV but unrelated to HCV disease and non-pathogenic, but its natural history and tissue tropism remain unclear. HPgV-2 is a unique RNA virus sharing the features of HCV and the first human pegivirus (HPgV-1 or GBV-C). Moreover, distinct from most RNA viruses such as HCV, HPgV-1 and human immunodeficiency virus (HIV), HPgV-2 exhibits much lower genomic diversity, with a high global sequence identity ranging from 93.5 to 97.5% and significantly lower intra-host variation than HCV. The mechanisms underlying the conservation of the HPgV-2 genome are not clear but may include efficient innate immune responses, low immune selection pressure and, possibly, the unique features of the viral RNA-dependent RNA polymerase (RdRP). In this review, we summarize the prevalence, pathogenicity and genetic diversity of HPgV-2 and discuss the possible reasons for the uniformity of its genome sequence, which should elucidate the implications of RNA virus fidelity for attenuated viral vaccines.

Microneedle-Based Glucose Sensor Platform: From Vitro to Wearable Point-of-Care Testing Systems.

Significant advanced have recently been made in exploiting microneedle-based (MN-based) diabetes devices for minimally invasive wearable biosensors and for continuous glucose monitoring. Within this emerging class of skin-worn MN-based sensors, the ISF can be utilized as a rich biomarker source to diagnose diabetes. While initial work of MN devices focused on ISF extraction, the recent research trend has been oriented toward developing in vivo glucose sensors coupled with optical or electrochemical (EC) instrumentation. This outlook highlights the essential characteristics of the sensing mechanisms, rational design, sensing properties, and applications. Finally, we describe the opinions about the challenge and prospects of optical and EC MN-based device platforms for the fabrication of wearable biosensors and their application potential in the future.