Screening for viral hepatitis carriage.

Viral hepatitis during pregnancy is common globally. In this review, we focus on the antenatal screen for hepatitis A, B, C and E, the prevention of mother-to-child transmission (MTCT) of hepatitis B and C, and the management of hepatitis A, B, C and E during pregnancy. Neonatal timely administration of hepatitis B immunoglobulin and hepatitis B vaccine is the cornerstone for preventing MTCT of hepatitis B virus (HBV), and perinatal antiviral prophylaxis with tenofovir disoproxil fumarate in mothers with positive HBeAg or HBV DNA >2 × 105 IU/ml also plays important roles in further reducing MTCT. Avoidance of risk practices in managing labor and delivery process of women with HCV infection may be useful to reduce MTCT of HCV. Early recognition of severe hepatic injury or liver failure associated with hepatitis viruses by regular liver function tests is critical to prevent maternal mortality associated with hepatitis.

CELLULOSE SYNTHASE-LIKE C proteins modulate cell wall establishment during ethylene-mediated root growth inhibition in rice.

The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.

Incidence of SARS-CoV-2 infection in children shortly after ending zero-COVID-19 policy in China on December 7, 2022: a cross-sectional, multicenter, seroepidemiological study.

Background: China discontinued the zero-COVID-19 policy on December 7, 2022, and then COVID-19 surged mid-December 2022 through mid-January 2023. However, the actual incidence was unknown. This study aimed to estimate the incidence of SARS-CoV-2 infection in children shortly after ending the zero-COVID-19 policy. Methods: This multicenter cross-sectional study included 1,065 children aged 8 months to 12 years from seven hospitals at six regions across Jiangsu province, based on the convenience sampling, from February 10 to March 10, 2023. Group I comprised 324 children aged 8 months-2 years without COVID-19 vaccination, group II consisted of 338 preschool children aged 3-5 years with varied vaccination history, and group III contained 403 primary school children aged 6-12 years with mostly vaccinated. The COVID-19 vaccines were composed of inactivated SARS-CoV-2. In addition, 96 children's sera collected in 2014 were included as negative controls. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (YHLO Biotech, Shenzhen, China). Results: None of the 96 children (5.1 ± 3.5 years; 58.3% boys) in 2014 was positive for anti-N/S1 IgG or IgM. Of the 1,065 children (5.0 ± 3.5 years; 56.0% boys), 988 (92.8%) were anti-N/S1 IgG positive but none was anti-N/S1 IgM positive. The positive rate of anti-N/S1 IgG in Group I, II, and III was 90.4, 88.5, and 98.3%, respectively, with significantly higher in group III than in groups I and II (p < 0.0001). The median antibody titers in group III (381.61 AU/ml) were much higher than that in group I (38.34 AU/ml) and II (51.88 AU/ml; p < 0.0001). Conclusion: More than 90% children experienced SARS-CoV-2 infection shortly after ending zero-COVID-19 policy in China, much higher than estimated infections by other studies. The widespread SARS-CoV-2 infection in unvaccinated children should be influential on the policy of COVID-19 vaccination in children in the future.

Can newborn infants with positive HIV soon after birth be diagnosed with intrauterine infection?

BACKGROUND: Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) can occur intrauterine, intrapartum, and postpartum. Currently, infants with confirmed positive results in virological tests before 48 h of age are defined as having intrauterine infection. AIM: We herein review the literature that identifies emerging challenges in diagnosing intrauterine HIV infection to rethink the current diagnostic criteria. FINDINGS: A number of reports have shown that some infants who were diagnosed with intrauterine HIV infection after birth became negative for HIV in the subsequent follow-ups, including negative HIV antibodies at the age of 12-18 months. Such "clearance" of HIV was attributed to various reasons: neonatal antiretroviral treatment (ART), false positivity, strong host immune response, or unknown factors in maternal breast milk. DISCUSSIONS: Positive HIV tests in newborn infants shortly after birth do not necessarily indicate HIV infection, because maternal HIV can enter fetal circulation intrapartum due to the repetitive, strong uterine contractions. The infants are therefore exposed to, but may not yet be infected with HIV at that time. The current diagnostic criteria cannot differentiate HIV exposure from HIV infection, leading to so-called "challenges in diagnosing intrauterine HIV infection". Those infants diagnosed with intrauterine infection who cleared HIV later were less likely to have been truly infected with HIV, but more likely to have been exposed to HIV. Moreover, we suggest that the determination of HIV antibody titers in infants' serial serum samples can provide valuable information to distinguish intrapartum exposure from intrauterine infection.

Maternal and Neonatal Outcomes of Twin Pregnant Women With Anemia.

The aim of this study was to investigate the prevalence of anemia in twin pregnancies and the influence of anemia on maternal and neonatal outcomes. This retrospective study included twin pregnant women who delivered in a tertiary hospital in China from January 2018 to December 2018. Patients were divided by WHO criteria (hemoglobin <11.0 g/dL): the anemic and nonanemic groups. Patients with anemia were further classified as recovered or unrecovered subgroup after oral iron therapy. Maternal and neonatal outcomes in women carrying twins were compared using Student's t test and the chi-squared test or the Fisher exact test. Univariable and multivariable logistic regression models were used to determine the association of maternal and neonatal characteristics with anemia. Linear regression analysis was used to estimate mean birth weight and gestational week. The prevalence of anemia was 42.6% (182/427) in twin pregnancies. The anemic group had higher rates of low 1-minute Apgar score (4.4% vs. 1.8%, p = .028), perinatal death (1.9% vs. 0.2%, p = .012) and neonatal intensive care unit (NICU) admission (27.2% vs. 20.2%, p = .017; adjusted OR, 1.478; 95% CI [1.07, 2.044]). The recovered subgroup had lower NICU admission rate (13.5% vs. 30.3%, p = .006; OR, 0.388; 95% CI [0.186, 0.809]), higher gestational week and birth weight (ß, 0.954 week; 95% CI [0.114, 1.794] and ß, 171.01 g; 95% CI [9.894, 332.126] respectively). The prevalence of anemia in twin gestation is high. Anemia is associated with adverse neonatal outcomes, and correction of anemia significantly improved the pregnancy outcomes.

Plant-on-chip: Core morphogenesis processes in the tiny plant Wolffia australiana.

A plant can be thought of as a colony comprising numerous growth buds, each developing to its own rhythm. Such lack of synchrony impedes efforts to describe core principles of plant morphogenesis, dissect the underlying mechanisms, and identify regulators. Here, we use the minimalist known angiosperm to overcome this challenge and provide a model system for plant morphogenesis. We present a detailed morphological description of the monocot Wolffia australiana, as well as high-quality genome information. Further, we developed the plant-on-chip culture system and demonstrate the application of advanced technologies such as single-nucleus RNA-sequencing, protein structure prediction, and gene editing. We provide proof-of-concept examples that illustrate how W. australiana can decipher the core regulatory mechanisms of plant morphogenesis.

Immunobiology and Host Response to HEV.

Hepatitis E virus (HEV) usually causes acute self-limiting hepatitis but sometimes leads to chronic infection in immunocompromised persons. HEV is not directly cytopathic. Immunologically mediated events after HEV infection are believed to play important roles in the pathogenesis and clearance of infection. The anti-HEV antibody responses have been largely clarified since the determination of major antigenic determinant of HEV, which is located in the C-terminal portion of ORF2. This major antigenic determinant also forms the conformational neutralization epitopes. Robust anti-HEV immunoglobulin M (IgM) and IgG responses usually develop 3-4 weeks after infection in experimentally infected nonhuman primates. In humans, potent specific IgM and IgG responses occur in the very early phase of the disease and are critical in eliminating the virus, in concert with the innate and adaptive T-cell immune responses. Testing anti-HEV IgM is valuable in the diagnosis of acute hepatitis E. The long-term persistence and protection of anti-HEV IgG provide the basis for estimating the prevalence of HEV infection and for the development of a hepatitis E vaccine. Although human HEV has four genotypes, all the viral strains are considered to belong to a single serotype. It is becoming increasingly clear that the innate and adaptive T-cell immune responses play critical roles in the clearance of the virus. Potent and multispecific CD4+ and CD8+ T cell responses to the ORF2 protein occur in patients with acute hepatitis E, and weaker HEV-specific CD4+ and CD8+ T cell responses appear to be associated with chronic hepatitis E in immunocompromised individuals.

Prevalence of antibody to hepatitis B surface antigen among qualified blood donors in Nanjing, China.

Universal infant hepatitis B vaccination has been implemented more than three decades. This study aimed to determine the prevalence of antibodies to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc) in qualified blood donors in Nanjing, China. Plasmas of 815 qualified blood donors, collected from February through May 2019, were measured for anti-HBs and anti-HBc by enzyme-linked immunosorbent assay. There were 449 (55.1%) male and 366 (44.9%) female blood donors, with a median age of 28.9 years (18-60). The seroprevalence of anti-HBs was 58.8%, with no significant difference in different genders and different age groups. The overall prevalence of anti-HBc was 7.0%, with an increasing trend with age, from 0% in 18-20 years old group to 17.9% in 51-60 years old group (χ2 = 46.7965, p < .0001). The prevalence of anti-HBc in donors born after the implementation of universal hepatitis B vaccination was significantly lower than that in donors born before (1.0% vs 15.5%; χ2 = 63.6033, p < .0001). Our data suggest that more than half of the blood donors in Nanjing are anti-HBs positive. Since a blood recipient usually receives more than one unit of red blood cells or plasma, passively acquired anti-HBs in blood recipients may neutralize hepatitis B virus potentially presented in blood donors with occult hepatitis B infection. In addition, the presence of anti-HBs and/or anti-HBc in blood donors may cause unique hepatitis B serological profile in blood recipients.

Minimal adverse outcomes of postnatal cytomegalovirus infection in term or moderate and late preterm infants.

Objective: The aim of study was to investigate at what extent breastfeeding and vaginal delivery can increase mother-to-child transmission of cytomegalovirus (CMV) and to observe the clinical outcomes of postnatal infection in term or moderate and late preterm infants. Methods: In this retrospective study of prospectively collected clinical data and serum samples, during 2012-2015, 380 women with CMV IgG positive/IgM negative and their 384 infants (4 twin pairs) with gestational age ≥32 weeks were included. CMV IgG and IgM were measured with enzyme-linked immunosorbent assay. Results: Of 384 infants followed up at 10.2 ± 2.3 months age, 177 (46.1%) were defined with CMV infection based on the presence of higher CMV IgG levels than in their mothers. The infection rate in 190 breastfed infants was higher than in 194 formula-fed infants (62.6% vs. 29.9%, P < 0.001). Vaginally delivered infants (172) had higher CMV infection rate than 212 infants delivered by caesarean section (55.2% vs. 38.7%, P = 0.001). Compared with formula feeding and caesarean section, breastfeeding and vaginal delivery increased postnatal CMV infection respectively (OR = 3.801, 95% CI 2.474-5.840, P < 0.001; OR = 1.818, 95% CI 1.182-2.796, P = 0.007). Nevertheless, compared to uninfected infants, CMV-infected infants had comparable height and body weight and showed no adverse effect on the liver enzymes. Conclusion: Breastfeeding and vaginal delivery can increase postnatal CMV infection; however, the infection does not influence the growth of the term infants or preterm infants with gestational age ≥32 weeks. Thus, breastfeeding should be encouraged in these infants regardless of maternal CMV IgG status.

Reduced antibody response to COVID-19 vaccine composed of inactivated SARS-CoV-2 in diabetic individuals.

Background: Patients with type 2 diabetes mellitus (T2DM) are at increased risk for COVID-19 related morbidity and mortality. Antibody response to COVID-19 vaccine in T2DM patients is not very clear. The present work aims to evaluate the antibody response to the inactivated SARS-CoV-2 vaccine in this population. Methods: Two groups of subjects with no history of SARS-CoV-2 infection were included: 63 T2DM patients and 56 non-T2DM controls. Each participant received two doses of inactivated COVID-19 vaccine. IgG antibodies against the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2 (anti-N/S IgG) and receptor binding domain (RBD) proteins (anti-RBD IgG) were quantitatively evaluated by the electrochemiluminescence immunoassays, respectively. Results: It was observed that the positive rates and titers of anti-N/S IgG and anti-RBD IgG in T2DM patients were significantly lower than those in controls, respectively (anti-N/S: 85.7 vs. 98.2%, P = 0.034; 25.48 vs. 33.58 AU/ml P = 0.011; anti-RBD: 85.7 vs. 96.4%, P = 0.044; 15.45 vs. 22.25 AU/ml, P = 0.019). Compared to non-T2DM subjects, T2DM patients with uncontrolled glycemia showed lower positive antibody rates and titers (anti-N/S IgG: 75% and 13.30 AU/ml; anti-RBD IgG: 75% and 11.91 AU/ml, respectively, all P < 0.05), while T2DM patients with controlled glycemia had similar positive antibody rates and titers (anti-N/S IgG: 94.3% and 33.65 AU/ml; and anti-RBD IgG: 94.3% and 19.82 AU/ml, respectively, all P > 0.05). Conclusion: In the analysis performed, the data indicate that T2DM patients with uncontrolled glycemia showed a lower level of IgG antibodies compared to non-diabetic controls and individuals with controlled glycemia when immunized with the inactivated COVID-19 vaccine.

COVID-19 vaccination coverage among adolescents aged 12-17 years in three provinces of eastern China: A cross-sectional survey, 2021.

High vaccination coverage is essential to prevent and control the spread of the COVID-19 epidemic. Currently, the real-world acceptance of COVID-19 vaccines among adolescents aged 12-17 years in China has not been reported. We aimed to assess the acceptance rate of COVID-19 vaccination among adolescents in eastern China and to identify factors associated with the intention to get vaccinated against COVID-19. We conduct a cross-sectional questionnaire survey among adolescents from three provinces in the eastern part of China from 16 August to 28 October 2021. The questionnaires were distributed to 2,100 students, and 2,048 students completed the questionnaires. The results showed that 98.4% (2,016/2,048) of adolescents had received at least one dose of the COVID-19 vaccine and 1.6% (32/2,048) declined the vaccination. The participants from rural districts, or whose parents were vaccinated, were more likely to accept the vaccine. The main reason for declining vaccination was worry about vaccine safety (25%). The main adverse event after the vaccination was pain at the injection site. In conclusion, the vaccine coverage rate reached 98.4% among the adolescents in this study, which met the criteria for herd immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The high vaccination rate is beneficial to the prevention and control of the COVID-19 pandemic.

Efficacy of the hepatitis B vaccine alone in the prevention of hepatitis B perinatal transmission in infants born to hepatitis B e antigen-negative carrier mothers.

Background: Vertical mother-to-child transmission (MTCT) of the hepatitis B virus (HBV) remains an important issue. Timely administration of hepatitis B immunoglobulin (HBIG) and of the HBV vaccine is effective in preventing MTCT in infants born to HBV-infected mothers. However, HBIG is often not easily available in low-income countries or regions. Methods: We compared in a retrospective cohort study the HBV vaccine efficacy alone and in combination with HBIG in preventing vertical MTCT in infants born to HBeAg-negative carrier mothers in Jiangsu province, China. Based on the administration of the HBV vaccine and HBIG shortly after birth, children were divided into two groups: Group 1, administration of the HBV vaccine alone, and Group 2, concurrent use of HBIG and of the HBV vaccine. Results: A total of 620 infants born to HBeAg-negative carrier mothers were enrolled into this study. Group 1 included 195 children who had received the HBV vaccine alone after birth, and Group 2, 425 children who had received both HBIG and the HBV vaccine. Children were followed up to the age of 68 and 42 months, respectively. MTCT of HBV occurred in 0% (0/195) in Group 1 (HBV vaccine alone) and 0% (0/425) in Group 2 (HBV vaccine and HBIG) (p = 1.00). Conclusion: In this retrospective cohort study, we found that HBV vaccination alone shortly after birth was effective in preventing MTCT of HBV in infants born to HBeAg-negative carrier mothers.

Attitudes and Factors Associated With Intention to the Third Dose of COVID-19 Vaccine Among Adolescents: A Cross-Sectional Survey in 3 Provinces of China.

OBJECTIVE: The COVID-19 caused a world pandemic, posing a huge threat to global health. Widespread vaccination is the most effective way to control the pandemic. Vaccination with the third dose of the COVID-19 vaccine is currently underway. We aimed to determine the attitude of adolescents toward the third dose of COVID-19 vaccine. METHODS: A structured questionnaire was administered between 16 August and 28 October 2021 among adolescents aged 12-17 years in three provinces of eastern region of China based on convenience sampling. The questionnaire was specifically developed to assess the adolescents' attitude toward and willingness to accept a third dose of the COVID-19 vaccine. RESULTS: In total, 94.3% (1742/1847) of the adolescents intended to accept the third dose of the COVID-19 vaccine. Age between 15-17 years, no worry about vaccine safety, confidence for vaccine effectiveness, and supporting opinion from parents were independently associated with acceptance of the third dose (p < 0.05). CONCLUSIONS: It is necessary for governments and school administrators to raise adolescents' and parents' awareness of the benefits and safety of the third dose of vaccination, which should be effective to increase the vaccination coverage among adolescents.

Self-Reported adverse events among Chinese healthcare workers immunized with COVID-19 vaccines composed of inactivated SARS-CoV-2.

Mass vaccination is critical to control the pandemic of coronavirus disease 2019 (COVID-19). Fear of adverse events (AEs) after COVID-19 vaccination is a main factor associated with vaccination hesitancy. We aimed to analyze AEs in healthcare workers (HCWs) vaccinated with COVID-19 vaccines (Aikewei or CoronaVac) composed of inactivated virus. We used a structured self-administered questionnaire to conduct two surveys on COVID-19 vaccination among HCWs in perinatal medicine and obstetrics/gynecology from April 5 to April 21, 2021. In total, 1392 HCWs who had received at least one vaccine dose were included. Of them, 1264 (90.8%) were females and 1047 (75.2%) received two doses. The overall incidence of any AEs after the first and second dose was 38.2% (532/1392) and 31.0% (325/1047) respectively (χ2 = 13.506, P = .0002). Female and HCWs aged 18-30 y were more likely to report AEs. The most common AEs were local reaction, accounting for 48.1% and 67.4% of all AEs after the first and second dose respectively. The systemic AEs were mainly neurological (9.8% and 4.8% after the first and second injection respectively) and flu-like symptoms (6.3% and 3.2%). Overall, most of AEs were mild, only 5.1% (after the first dose) and 2.8% (after the second dose) of individuals with AEs received symptomatic treatment or sick leaves, and none of them required hospitalization. Our data added more evidence that inactivated COVID-19 vaccines are highly safe. The data are valuable to overcome vaccine hesitancy associated with concerns about the safety of COVID-19 vaccines.

[68Ga]Ga-PSMA-11 PET/CT has potential application in predicting tumor HIF-2α expression and therapeutic response to HIF-2α antagonists in patients with RCC.

OBJECTIVE: To evaluate the efficacy of parameters derived from [68Ga]Ga-PSMA-11 PET/CT images in predicting pathological HIF-2α expression in primary tumors among patients with renal cell carcinoma (RCC). METHODS: Fifty-three RCC patients with preoperative [68Ga]Ga-PSMA-11 PET/CT scans and complete surgical specimens were retrospectively enrolled in this study. Radiographic parameters were obtained from PET/CT images, and immunohistochemistry was used to measure the expression of HIF-2α and PSMA. Continuous variables and categorical variables were analyzed by the Mann-Whitney U test and chi-square test, respectively. ROC analysis was used to test the efficacy of several preoperative parameters in identifying pathological HIF-2α expression. Univariable logistic regression analyses were performed for significant parameters to predict pathological HIF-2α expression in RCC. RESULTS: Of the 53 tumors, 29 (54.7%) had high expression of HIF-2α. The SUVmax was significantly different in the HIF-2α expression subgroups (p < 0.001). SUVmax emerged as the most significant parameter to differentiate HIF-2α expression subgroups (high vs. low), with the AUC of 0.93 (95% CI 0.85-1.00, p < 0.001), sensitivity of 90%, and specificity of 88%. Furthermore, SUVmax was confirmed as the most significant predictor of HIF-2α expression level by univariable logistic regression model analysis (odds ratio 1.39, 95% CI 1.17-1.65, p < 0.001). Consistent with the radiographic results of [68Ga]Ga-PSMA-11 PET/CT, the staining intensity of pathological PSMA was significantly higher in HIF-2α-high-expressing tumors (p = 0.003). CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT was superior in identifying pathological HIF-2α expression in primary tumors of RCC patients, demonstrating its potential application in predicting responses to HIF-2α antagonists. KEY POINTS: • [68Ga]Ga-PSMA-11 PET/CT could potentially predict the HIF-2α expression of primary tumors among patients with RCC. • SUVmaxof [68Ga]Ga-PSMA-11 PET/CT was the most significant predictor of HIF-2α expression level. • This probability could help predict the therapeutic response of patients with RCC to HIF-2α antagonists.

Identified human breast milk compositions effectively inhibit SARS-CoV-2 and variants infection and replication.

The global pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confers great threat to public health. Human breast milk is a complex nutritional composition to nourish infants and protect them from different kinds of infectious diseases including COVID-19. Here, we identified that lactoferrin (LF), mucin1 (MUC1), and α-lactalbumin (α-LA) from human breast milk inhibit SARS-CoV-2 infection using a SARS-CoV-2 pseudovirus system and transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). In addition, LF and MUC1 inhibited multiple steps including viral attachment, entry, and postentry replication, whereas α-LA inhibited viral attachment and entry. Importantly, LF, MUC1, and α-LA possess potent antiviral activities toward variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), and B.1.617.1 (kappa). Taken together, our study provides evidence that human breast milk components (LF, MUC1, and α-LA) are promising antiviral and potential therapeutic candidates warranting further development for treating COVID-19.