Cryogenic Electron-Beam Writing for Perovskite Metasurface.

Halide perovskites (HPs) metasurfaces have recently attracted significant interest due to their potential to not only further enhance device performance but also reveal the unprecedented functionalities and novel photophysical properties of HPs. However, nanopatterning on HPs is critically challenging as they are readily destructed by the organic solvents in the standard lithographic processes. Here, we present a novel, subtle, and fully nondestructive HPs metasurface fabrication strategy based on cryogenic electron-beam writing. This technique allows for high-precision patterning and in situ imaging of HPs with excellent compatibility. As a proof-of-concept, broadband absorption enhanced metasurfaces were realized by patterning nanopillar arrays on CH3NH3PbI3 film, which results in photodetectors with approximately 14-times improvement on responsivity and excellent stability. Our findings highlight the great feasibility of cryogenic electron-beam writing for producing perovskite metasurface and unlocking the unprecedented photoelectronic properties of HPs.

A systematic review and meta-analysis of herpes zoster occurrence/recurrence after COVID-19 infection and vaccination.

To inform surveillance, prevention, and management strategies for the varicella zoster virus (VZV) during the COVID-19 pandemic, this study aimed to evaluate the risk of herpes zoster (HZ) occurrence/recurrence following COVID-19 infection and vaccination. A comprehensive search across seven databases was conducted up to January 31, 2024, to identify studies relevant to the occurrence of HZ following COVID-19 infection and vaccination. The meta-analysis included five studies on postinfection HZ and 13 studies on postvaccination HZ. Patients infected with COVID-19 had a 2.16-fold increased risk of HZ (95% confidence interval [CI]: 1.24-3.76) than uninfected individuals. However, there was no significant association between COVID-19 vaccination and the risk of HZ compared to controls, with a relative risk (RR) of 1.08 (95% CI: 0.84-1.39). Furthermore, a descriptive analysis of 74 postinfection and 153 postvaccination HZ studies found no significant differences on gender or age (<50 and ≥50 years) following COVID-19 infection. Notably, 44.0% of the HZ cases postinfection appeared within the first week, with 69.5% resolving within 10 days, predominantly presenting as skin lesions. In the postvaccination group, the majority (60.1%) developed HZ after the first dose and 66.7% occurred within 1 week. Moreover, 44.6% resolved within 10 days and 50.0% within a month, primarily exhibiting skin lesions and postherpetic neuralgia. The study found that COVID-19 infection increases the risk of HZ, but the COVID-19 vaccine does not. Further study is needed to explore the association between COVID-19 and HZ.

Improving the Accuracy of Direction of Arrival Estimation with Multiple Signal Inputs Using Deep Learning.

In this paper, an innovative cyclic noise reduction method and an improved CAPON algorithm (also the called minimum variance distortionless response (MVDR) algorithm) are proposed to improve the accuracy and reliability of DOA (direction of arrival) estimation. By processing the eigenvalues obtained from the covariance matrix of the received signal, the signal-to-noise ratio (SNR) can be increased by up to 5 dB by the cyclic noise reduction method, which will improve the DOA estimation accuracy. The improved CAPON algorithm has a convolution neural network (CNN) structure, whose input is the processed covariance matrix of the received signal, and the CAPON spectral value is used as the training label to obtain the estimated spatial spectrum. It retains the advantages of the CAPON algorithm, which can achieve blind source estimation, and simulations show that the proposed algorithm exhibits a better performance than the traditional algorithm in conditions of various SNRs and snapshot numbers. The simulation results show that, based on a certain SNR, the root mean square error (RMSE) of the improved CAPON algorithm can be reduced from 0.86° to 0.8° compared to traditional algorithms, and the angle estimation error can be decreased by up to about 0.3°. With the help of the cyclic noise reduction method, the angle estimation error decreases from 0.04° to 0.02°.

Avian influenza A virus H7N9 in China, a role reversal from reassortment receptor to the donator.

Reassortment can introduce one or more gene segments of influenza A viruses (IAVs) into another, resulting in novel subtypes. Since 2013, a new outbreak of human highly pathogenic avian influenza has emerged in the Yangtze River Delta (YRD) and South-Central regions of China. In this study, using Anhui province as an example, we discuss the possible impact of H7N9 IAVs on future influenza epidemics through a series of gene reassortment events. Sixty-one human H7N9 isolates were obtained from five outbreaks in Anhui province from 2013 to 2019. Bioinformatics analyses revealed that all of them were characterized by low pathogenicity and high human or mammalian tropism and had introduced novel avian influenza A virus (AIV) subtypes such as H7N2, H7N6, H9N9, H5N6, H6N6, and H10N6 through gene reassortment. In reassortment events, Anhui isolates may donate one or more segments of HA, NA, and the six internal protein-coding genes for the novel subtype AIVs. Our study revealed that H7N9, H9N2, and H5N1 can serve as stable and persistent gene pools for AIVs in the YRD and South-Central regions of China. Novel AIV subtypes might be generated continuously by reassortment. These AIVs may have obtained human-type receptor-binding abilities from their donors and prefer binding to them, which can cause human epidemics through accidental spillover infections. Facing the continual threat of emerging avian influenza, constant monitoring of AIVs should be conducted closely for agricultural and public health.

Preferences for Sexually Transmitted Infection and Cancer Vaccines in the United States and in China.

OBJECTIVES: This study assessed preferences for hypothetical vaccines for children in 2 large vaccine markets according to how the vaccine-preventable disease is transmitted via a discrete choice experiment. METHODS: Surveys in China (N = 1350) and the United States (N = 1413) were conducted from April to May 2021. The discrete choice experiment included attributes of cost, age at vaccination, transmission mode of the vaccine-preventable disease, and whether the vaccine prevents cancer. Preference utilities were modeled in a Bayesian, multinomial logistic regression model, and respondents were grouped by vaccine preference classification through a latent class analysis. RESULTS: Individuals favored vaccines against diseases with transmission modes other than sexual transmission (vaccine for sexually transmitted infection [STI] vs airborne disease, in the United States, odds ratio 0.71; 95% credible interval 0.64-0.78; in China, odds ratio 0.76; 95% credible interval 0.69-0.84). The latent class analysis revealed 6 classes: vaccine rejecters (19% in the United States and 8% in China), careful deciders (18% and 17%), preferring cancer vaccination (20% and 19%), preferring vaccinating children at older ages (10% and 11%), preferring vaccinating older ages, but indifferent about cancer vaccines (23% and 25%), and preferring vaccinating children at younger ages (10% and 19%). Vaccine rejection was higher with age in the United States versus more vaccine rejection among those at the age of 18 to 24 and ≥ 64 years in China. CONCLUSION: The public had strong preferences against giving their child an STI vaccine, and the class preferring a cancer vaccine was less accepting of an STI vaccine. Overall, this study points to the need for more education about how some STI vaccines could also prevent cancers.

Water-Stable Hybrid Lead-Free Perovskite for Negative Temperature Coefficient Thermistors.

Negative temperature coefficient (NTC) thermistors feature higher sensitivities and faster response speeds and thereby have particular applications in many fields. However, current NTC thermistors are mostly based on inorganic ceramic materials, which show obvious drawbacks in material synthesis, property modulation, and flexible film fabrication. Herein, we report, for the first time, the promising application of an inorganic-organic hybrid NTC thermistor. A new lead-free hybrid iodo bismuthate [1,1',1″-(benzene-1,3,5-triyl)tris(3-methyl-1H-imidazol-3-ium)]Bi2I9 [denoted as (Me3TMP)Bi2I9] was synthesized by a "double-free" strategy. (Me3TMP)Bi2I9 features a lead-free binuclear bismuth iodine anion charge compensated by a "classic hydrogen-bond-free" cation. (Me3TMP)Bi2I9 exhibits remarkable stability in water and UV light irradiation and shows the largest temperature sensitivity coefficient among all reported NTC materials. Theoretical calculation and detailed structural analysis disclose that the seriously distorted (BiI6) octahedra are responsible for the intriguing NTC effect for (Me3TMP)Bi2I9.

Epidemiological and clinical characteristics of psittacosis among cases with complicated or atypical pulmonary infection using metagenomic next-generation sequencing: a multi-center observational study in China.

BACKGROUND: Chlamydia psittaci (C. psittaci) causes parrot fever in humans. Development of metagenomic next-generation sequencing (mNGS) enables the identification of C. psittaci. METHODS: This study aimed to determine the epidemiological and clinical characteristics of parrot fever cases in China. A multi-center observational study was conducted in 44 tertiary and secondary hospitals across 14 provinces and municipalities between April 2019 and October 2021. RESULTS: A total of 4545 patients with complicated or atypical pulmonary infection were included in the study, among which the prevalence of C. psittaci was determined to be 2.1% using mNGS. The prevalence of C. psittaci was further determined across demographic groups and types of specimens. It was significantly higher in patients with senior age (2.6% in those > 50 years), winter-spring (3.6%; particularly in December, January, and February), and southwestern (3.4%) and central and southern China (2.7%) (each P < 0.001). Moreover, the prevalence was the highest in bronchoalveolar lavage fluid (BALF) (2.9%), compared with sputum (1.1%) and peripheral blood specimens (0.9%). Additionally, co-infection of principal microorganisms was compared. Certain microorganisms were more likely to co-infect in parrot fever cases, such as Candida albicans in BALF (26.7%) and peripheral blood (6.3%), compared with non-parrot fever cases (19.7% and 1.3%); however, they did not significantly differ (each P > 0.05). CONCLUSION: Parrot fever remains low in patients with complicated or atypical pulmonary infection. It is likely to occur in winter-spring and southwestern region in China. BALF may be the optimal specimen in the application of mNGS. Co-infection of multiple microorganisms should be further considered.

Suppression of Phase Transitions in Perovskite Thin Films through Cryogenic Electron Beam Irradiation.

Organic-inorganic hybrid perovskites (OIHPs) with superior optoelectronic properties have emerged as revolutionary semiconductor materials for diverse applications. A fundamental understanding of the interplay between the microscopic molecular-level structure and the macroscopic optoelectronic properties is essential to boost device performance toward theoretical limits. Here, we reveal the critical role of CH3NH3+ (MA) in the regulation of the physicochemical and optoelectronic properties of a MAPbI3 film irradiated by an electron beam at 130 K. The order-to-disorder transformation of the MA cation not only leads to a notably enhanced photoluminescence emission but also results in the suppression of the orthorhombic phase down to 85 K. Taking advantage of the regulation of MA cation dynamics, we demonstrate a perovskite photodetector with 100% photocurrent enhancement and long-term stability exceeding one month. Our study provides a powerful tool for regulating the optoelectronic properties and stabilities of perovskites and highlights potential opportunities related to the organic cation in OIHPs.

Determination of the Predictive Roles and Potentially Pathogenic Antigen Epitopes of α-Enolase Related to the Development of Miscarriage in Females with Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) is a common endocrine disease which causes a significantly increased risk of miscarriage. Our recent study has shown that the increased ENO1 autoantibody (ENO1Ab) expression in an experimental AIT mouse model was induced by thyroglobulin (Tg) immunization only. In this study, we explored the potential roles of ENO1Ab in miscarriage occurrence among AIT women, and the specific epitopes of ENO1 targeted by ENO1Ab. A total of 432 euthyroid pregnant participants were selected from the project of Subclinical Hypothyroid during Early Pregnancy, including 48 women with AIT and miscarriage, 96 with miscarriage but no AIT, 96 with AIT but no miscarriage, and 192 without either AIT or miscarriage. The enzyme-linked immunosorbent assay was used to determine the serum levels of total IgG against ENO1 and 18 predicted antigen epitopes of ENO1. The results showed that women with AIT and miscarriage had the highest serum levels of ENO1Ab compared to the other groups. Logistic regression analysis showed that the serum ENO1Ab was an independent risk factor for miscarriage, especially among AIT females. The serum level of total IgG against the predicted epitope peptide 6 (i.e., P6 and aa168-183) of ENO1 was significantly increased in women with AIT and miscarriage when compared with those of both the AIT non-miscarriage group and non-AIT miscarriage group. This pilot study suggests that serum ENO1Ab may have a fair predictive value for AIT-related miscarriage, and the autoantibody specific to P6 epitope may especially be more specifically related to this disorder.

Codon usage of host-specific P genotypes (VP4) in group A rotavirus.

BACKGROUND: Group A rotavirus (RVA) is a common causative agent of acute gastroenteritis in infants and young children worldwide. RVA P genotypes, determined by VP4 sequences, have been confirmed to infect humans and animals. However, their codon usage patterns that are essential to obtain insights into the viral evolution, host adaptability, and genetic characterization remained unclear, especially across animal hosts. RESULTS: We performed a comprehensive codon usage analysis of eight host-specific RVA P genotypes, including human RVA (P[4] and P[8]), porcine RVA (P[13] and P[23]), and zoonotic RVA (P[1], P[6], P[7] and P[19]), based on 233 VP4 complete coding sequences. Nucleotide composition, relative synonymous codon usage (RSCU), and effective number of codons (ENC) were calculated. Principal component analysis (PCA) based on RSCU values was used to explore the codon usage patterns of different RVA P genotypes. In addition, mutation pressure and natural selection were identified by using ENC-plot, parity rule 2 plot, and neutrality plot analyses. All VP4 sequences preferred using A/U nucleotides (A: 0.354-0.377, U: 0.267-0.314) than G/C nucleotides across genotypes. Similarly, majority of commonly used synonymous codons were likely to end with A/U nucleotides (A: 9/18-12/18, U: 6/18-9/18). In PCA, human, porcine, and zoonotic genotypes clustered separately in terms of RSCU values, indicating the host-specific codon usage patterns; however, porcine and zoonotic genotypes were partly overlapped. Human genotypes, P[4] and P[8], had stronger codon usage bias, as indicated by more over-represented codons and lower ENC, compared to porcine and zoonotic genotypes. Moreover, natural selection was determined to be a predominant driver in shaping the codon usage bias across the eight P genotypes. In addition, mutation pressure contributed to the codon usage bias of human genotypes. CONCLUSIONS: Our study identified a strong codon usage bias of human RVA P genotypes attributable to both natural selection and mutation pressure, whereas similar codon usage bias between porcine and zoonotic genotypes predominantly attributable to natural selection. It further suggests possible cross-species transmission. Therefore, it warrants further surveillance of RVA P genotypes for early identification of zoonotic infection.

The effects of maternal anti-alpha-enolase antibody expression on the brain development in offspring.

Anti-alpha-enolase autoantibodies have not only been found to play an important role in autoimmune diseases but also cause neurological damage in adults. In this study, a pregnant mouse model with high serum alpha-enolase (ENO1)-specific antibody (ENO1Ab) was established by immunization with ENO1 protein to explore the effects of maternal circulatory ENO1Ab on the brain development in offspring. The pups showed impaired learning and memory abilities with obviously thinner tight junctions in the brain tissue. IgG deposits colocalized with both ENO1 protein and complement 3 (C3), and the membrane attack complex was obviously detectable in the brain tissues of pups from dams with high serum ENO1Ab expression. Our findings suggest that highly expressed ENO1Ab in the maternal circulation can pass through the blood-placenta-barrier and the compromised blood-brain barrier into the brain tissues of offspring and may cause neurological development impairment mainly through complement-dependent cytotoxicity.

Measurement of dynamic atomic polarizabilities of Al at 19 wavelengths from 420†nm to 680†nm in electrical exploding wire experiments.

The dynamic polarizabilities of Al atom at 19 wavelengths from 420 nm to 680 nm are measured experimentally for the first time. A 15 µm diameter Al wire is heated to the gas/ microdrop stage using a 3 kA, 25 ns pulsed current, and the energy deposition when the resistive voltage reaches its peak is 4.7 eV·atom-1, which is higher than the atomization enthalpy of Al but much lower than its first ionization potential. Two laser interferometric images of the Al gas are obtained simultaneously using a 532 nm laser and an optical parametric oscillator laser. Then an integrated phase method is used to reconstruct the Al atomic linear density distribution based on the known atomic polarizability at 532 nm, which acts as a bridge between the two interferograms to obtain the relative atomic polarizability value at a specific wavelength with respect to the value at 532 nm. The measured dynamic polarizability of Al atom decreases from 13.5×10-24 cm3 to 9.4×10-24 cm3 as the wavelength increases from 420 nm to 680 nm with a measurement error of approximately ±10%. The experimental result fits well with an uncoupled Hartree-Fock approximation, and the reconstructed static polarizability of 8.13 ± 0.79×10-24 cm3 is well matched with reference measurement results.

Molecular characteristics of a coxsackievirus A12 strain in Zhejiang of China, 2019.

BACKGROUND: Enterovirus A (EV-A), such as enterovirus A71 (EV-A71), generally causes hand, foot, and mouth disease (HFMD). However, limited studies focused on uncommon enterovirus serotypes such as coxsackievirus A12 (CV-A12). This study aimed to provide evidence to determine the molecular characteristics of a CV-A12 strain isolated in Zhejiang province, China. METHODS: In routine surveillance of HFMD, we identified a child case with CV-A12 infection in 2019 in Zhejiang province, China. Enterovirus was examined by using real-time reverse transcription-PCR (qRT-PCR). A partial VP1 sequence was amplified to determine the serotype, and then a full-length CV-A12 genome was sequenced. Nucleotide and amino acid similarity was calculated with those CV-A12 strains available in GenBank. Recombination was detected using RDP 4 and SimPlot. Furthermore, phylogenetic analysis was conducted by using BEAST 1.10, and protein modeling was performed with I-TASSER webserver. RESULTS: A full-length CV-A12 genome PJ201984 was isolated in a Chinese child with HFMD. The similarities with complete coding sequences of the CV-A12 strains in GenBank ranged between 79.3-100% (nucleotide) and 94.4-100% (amino acid), whereas it was 88.7-100.0% (nucleotide) and 97.2-100% (amino acid) when excluding the CV-A12 prototype strain Texas-12. In PJ201984, amino acid variations were more divergent in P2 and P3 regions than those in P1; the majority of those variations in VP1 (13/15) and VP4 (7/8) were similar to those documented in recently isolated CV-A12 strains in China. Furthermore, recombination was identified in P2 region, which involved a CV-A5 strain collected in China. Phylogenetic analysis revealed that PJ201984 clustered together with multiple CV-A12 strains isolated in China and the Netherlands during 2013-2018, as compared to another cluster consisting of CV-A12 strains in China and France during 2009-2015. Additionally, protein models of VP1 and VP4 in PJ201984 were well predicted to be similar to VP1 protein of EV-A71 and VP4 protein of coxsackievirus A21, respectively. CONCLUSIONS: The full-length CV-A12 genome was characterized to have common recombination in P2 region and be phylogenetically related to those CV-A12 strains isolated in recent years, suggesting a continual spread in China. It warrants strengthening the routine surveillance for uncommon enterovirus serotypes, particularly on possible recombination and variation.

Methylated Septin9 has moderate diagnostic value in colorectal cancer detection in Chinese population: a multicenter study.

BACKGROUND: The detection rate of methylated Septin9 (mSEPT9) in colorectal cancer (CRC) is varied greatly across the studies. This study aimed to evaluate the diagnostic ability of mSEPT9 in CRC, and compare the diagnostic efficacy with fecal immunochemical test (FIT). METHODS: 326 subjects from four centers were prospectively recruited, including 179 CRC and 147 non-CRC subjects. The plasma was collected for mSEPT9 and CEA, AFP, CA125, CA153 and CA199 test, and fecal samples for FIT tests. Sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic curve were calculated to evaluate the diagnostic value of each biomarker. RESULTS: The positive rate in mSEPT9 and FIT, and the level of CEA, CA125 and CA199 were significantly higher in CRC compared with non-CRC subjects. The mSEPT9 positive rate was not associated with TNM stage and tumor stage. The sensitivity, specificity and AUC of mSEPT9 in diagnostic CRC were 0.77, 0.88 and 0.82, respectively, while the value in FIT was 0.88, 0.80 and 0.83, respectively. mSEPT9 and FIT have higher AUC value than that of CEA, CA125 and CA199. Combination of both mSEPT9 and FIT positive increased sensitivity and AUC to 0.98 and 0.83, respectively, but the specificity was declined. mSEPT9 has a slightly low sensitivity in diagnosis of colon cancer (0.87) compared with rectal cancer (0.93). CONCLUSION: mSEPT9 demonstrated moderate diagnostic value in CRC detection, which was similar to the FIT but superior to the CEA, CA125 and CA199. Combination of mSEPT9 and FIT further improved diagnostic sensitivity in CRC. TRIAL REGISTRATION: ChiCTR2000038319.

Long-term immune responses in patients with confirmed novel coronavirus disease-2019: a 9-month prospective cohort study in Shanghai, China.

BACKGROUND: The duration of antibodies against SARS-CoV-2 in Covid-19 patients remains uncertain. Longitudinal serological studies are needed to prevent disease and transmission of the virus. METHODS: In 2020, 414 blood samples were tested, obtained from 157 confirmed Covid-19 patients, in a prospective cohort study in Shanghai. RESULTS: The seropositive rate of IgM peaked at 40.5% (17/42) within 1 month after illness onset and then declined. The seropositive rate of IgG was 90.6% (58/64) after 2 months, remained above 85% from 2 to 9 months and was 90.9% (40/44) after 9 months. Generalized estimating equations models suggested that IgM (P < 0.001) but not IgG significantly decreased over time. Age ≥ 40 years (adjusted odds ratio [aOR] 4.531; 95% confidence interval [CI] 1.879-10.932), and cigarette smoking (aOR 0.344; 95% CI 0.124-0.951) were associated with IgG, and age ≥ 40 years (aOR 2.820; 95% CI 1.579-5.036) was associated with IgM. After seroconversion, over 90% and 75.1% of subjects were estimated to remain IgG-positive 220 and 254 days, respectively. Of 1420 self-reported symptoms questionnaires, only 5% reported symptoms 9 months after onset. CONCLUSIONS: In patients with a history of natural infection, anti-SARS-CoV-2 IgG is long-lived, being present for at least 9 months after illness onset. The long duration of natural immunity can mitigate and eliminate Covid-19 and the ongoing pandemic.

Willingness to pay for HPV vaccine among female health care workers in a Chinese nationwide survey.

BACKGROUND: Payment methods for human papillomavirus (HPV) vaccine could substantially influence vaccination behavior. In China, HPV vaccination uptake remains currently low. This study aims to determine willingness to pay (WTP) for HPV vaccines among Chinese female health care workers under different payment scenarios. METHODS: This is a nationwide online survey recruiting female health care workers aged 18-45 years from 31 provinces throughout China. We collected the respondents' vaccination status of HPV vaccines and their sociodemographics. Two WTPs were defined and estimated in the study. A general WTP for HPV vaccination was determined using the contingent valuation method with double dichotomous choice bidding. A WTP out-of-pocket was estimated for each HPV vaccine under two scenarios, including partial coverage by governmental subsidy or partial incorporation in basic medical insurance. Accordingly, a multivariable linear regression model was employed to determine the association between sociodemographis and general WTP. Then the maximum WTP out-of-pocket was compared among the respondents' attitude shift towards HPV vaccination, payment scenarios, and levels of vaccine attributes, using non-parametric Kruskal-Wallis test. RESULTS: A total of 15,969 respondents were included in the study. The median general WTP was 2000 CNY (interquartile range, 1000-3200 CNY), positively associated with younger age, unmarried status, higher monthly income, fewer children, more positive vaccination behavior, working in tertiary hospital, higher local GDP and HDI (each P < 0.05). Moreover, the median WTP out-of-pocket was 1250 CNY (540-2000 CNY). It was significantly higher for vaccines partly covered by governmental subsidy (median, 1250 CNY; interquartile range, 560-2000 CNY), imported vaccines (1260 CNY; 630-1960 CNY), and 9-valent vaccines (1400 CNY; 750-2240 CNY) (each P < 0.001). Additionally, majority of respondents did not change their attitude towards HPV vaccination between two payment scenarios; those remaining with more expensive HPV vaccines (51.1%) had higher WTP out-of-pocket (1400 CNY; 560-2250 CNY) than those with cheaper vaccines (39.0%) (1120 CNY; 490-1960 CNY) (P < 0.001). CONCLUSION: Chinese female health care workers have high WTP for HPV vaccines. A direct public funding for HPV vaccination is more preferable. Our findings may facilitate the adjustment of HPV vaccination strategy and payment mechanism in China.

The distribution of hepatitis C virus infection in Shanghai, China: a time-spatial study.

BACKGROUND: Shanghai, as a pilot city of China to achieve the goal of eliminating hepatitis C, its strategy of allocating medical resources is a pressing problem to be solved. This study aims to infer the time-spatial clustering patterns of HCV-infected cases, and grasp the dynamic genotype distribution of HCV, thereby inform elimination strategies of HCV with efficacy and efficiency. METHODS: Reported HCV cases including their demographic information in Shanghai city from 2005 to 2018 were released from the National Infectious Disease Reporting Information System, population data at community scale, geographical layers of hospitals, communities and districts were gathered from former research. Blood samples of HCV-infected individuals were collected during 2014-2018 from 24 sentinel hospitals, HCV-antibody test, qualitative nucleic acid test and NS5B/5'UTR gene amplification were performed accordingly to determine the genotypes of the specimen. Furthermore, global and local spatial self-correlation analysis of both acute and chronic HCV infections were conducted at community scale year by year, then time-spatial clusters of acute and chronic HCV infections and HCV genotype distribution of specimen collected from sentinel hospitals by districts were mapped by using Arcmap10.1. RESULTS: A total of 2631 acute HCV cases and 15,063 chronic HCV cases were reported in Shanghai from 2005 to 2018, with a peak in 2010 and 2017, respectively. The mean age of chronic HCV patients was 49.70 ± 14.55 years, 3.34 ± 0.32 years older than the acute (t = 10.55, P-value < 0.01). The spatial distribution of acute HCV infection formed one primary cluster (Relative Risk = 2.71), and the chronic formed one primary cluster and three secondary clusters with Relative Risk ranged from 1.94 to 14.42, meanwhile, an overlap of 34 communities between acute and chronic HCV clusters were found with time period spans varied from 6 to 12 years. Genotype 1 (N = 257, 49.71%) was the most prevalent HCV genotype in Shanghai, genotype 3 infections have increased in recent years. Baoshan district presented cluster of acute HCV and the highest proportion of genotype 2, Pudong new area was the cluster of chronic HCV and occupied the highest proportion of genotype 3. CONCLUSIONS: Despite the low prevalence of HCV infection, it is still needed to push forward the elimination process in Shanghai, as there is a certain amount of HCV infected people waiting to be treated. The time-spatial clustering patterns and the dynamic of HCV genotype distribution together indicated a changing constitution of different transmission routes of HCV infection, thus, a focused strategy may be needed for high-risk population related to genotype 3 infection like drug users, in addition to an enforcement of the existing measures of preventing the iatrogenic and hematogenic transmission of HCV.

The burden of hand, foot, and mouth disease among children under different vaccination scenarios in China: a dynamic modelling study.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common illness in young children. A monovalent vaccine has been developed in China protecting against enterovirus-71, bivalent vaccines preventing HFMD caused by two viruses are under development. OBJECTIVE: To predict and compare the incidence of HFMD under different vaccination scenarios in China. METHODS: We developed a compartmental model to capture enterovirus transmission and the natural history of HFMD in children aged 0-5, and calibrated to reported cases in the same age-group from 2015 to 2018. We compared the following vaccination scenarios: different combinations of monovalent and bivalent vaccine; a program of constant vaccination to that of pulse vaccination prior to seasonal outbreaks. RESULTS: We estimate 1,982,819, 2,258,846, 1,948,522 and 2,398,566 cases from 2015 to 2018. Increased coverage of monovalent vaccine from 0 to 80% is predicted to decrease the cases by 797,262 (49.1%). Use of bivalent vaccine at an 80% coverage level would decrease the cases by 828,560. Use of a 2.0× pulse vaccination for the bivalent vaccine in addition to 80% coverage would reduce cases by over one million. The estimated R0 for HFMD in 2015-2018 was 1.08, 1.10, 1.35 and 1.17. CONCLUSIONS: Our results point to the benefit of bivalent vaccine and using a pulse vaccination in specific months over routine vaccination. Other ways to control HFMD include isolation of patients in the early stage of dissemination, more frequent hand-washing and ventilation, and better treatment options for patients.

Identification of Enterococcus faecalis in a patient with urinary-tract infection based on metagenomic next-generation sequencing: a case report.

BACKGROUND: Urinary tract infection (UTI) caused by various pathogenic microorganisms is ubiquitous in the parts of the urinary system such as kidney, ureter, bladder, and urethra. Currently, clinical detection of UTI is mainly focused on urine culture; however, the diagnostic value of urine culture remains limited due to the time-consuming procedure and low detection rate, especially in patients who have used antibiotics. Generally, treatment for UTI relies on empirical medication rather than pathogen diagnosis, which leads to the inappropriate use of antimicrobial agents and a significant increase in resistant strains. Comparatively, metagenomic next-generation sequencing (mNGS) is capable of overcoming the disadvantages of clinical culture, and identifying pathogens for further treatment. CASE PRESENTATION: A 33-year-old male patient was admitted to hospital with a high fever and chills. None of his autoimmune disease or thyroid function related indicators were positive, and he had no risk of endocarditis. His white blood cell count, C-reactive protein, procalcitonin, interleukin 6, and neutrophil proportion were markedly elevated. He was initially diagnosed as having an infection of unknown etiology. Since empirical treatment of Sulperazon and Metronidazole did not relieve his symptoms, both the blood and urine specimens were examined using traditional culture, serological testing, and mNGS assay. Traditional culture and serological testing produced negative results, while the mNGS assay revealed the presence of a potential pathogen, Enterococcus faecalis, in the urine specimen, which was further confirmed by both Sanger sequencing and qPCR analysis. A CT scan of the patient's whole abdomen showed stones in the right kidney. Once targeted antibiotic therapy was administered, the patient recovered quickly. CONCLUSIONS: Our case illustrated that mNGS, as a novel culture-independent approach, demonstrated the capability of rapid, sensitive, and accurate pathogen identification. Furthermore, this technology provides strong support for guiding clinicians to determine appropriate treatment.

RBM4-Nova1-SRSF6 splicing cascade modulates the development of brown adipocytes.

Alternative splicing (AS) is a pivotal mechanism for the expansion of gene diversity, which determines the cellular fate or specification. However, the effect of AS networks on brown adipogenesis has not been comprehensively investigated. In this study, we identified the discriminative splicing profiles of RNA-binding motif protein 4a-knockout (RBM4a-/-) brown adipocytes (BAs) and compared them with those of their wild-type counterparts through deep RNA-sequencing. Among these candidates, RBM4a ablation enhanced the relative level of exon 4-excluded neuro-oncological ventral antigen 1 (Nova1-4) transcripts, which were predominantly generated in embryonic BAs. By contrast, most of the Nova1 transcripts were exon 4-included (Nova1+4) in mature BAs. The Nova1 isoforms exhibited differential effects on repressing the development of BAs. Moreover, overexpression of Nova1 proteins reduced the serine/arginine splicing factor 6 (SRSF6) level by enhancing the generation of intron 2-included (SRSF6+intron 2) transcripts, which are a putative candidate of the AS-coupled nonsense-mediated decay mechanism. Furthermore, we observed the positive effect of SRSF6 on BA development. These results highlight the hierarchical role of RBM4a in an AS cascade that manipulates brown adipogenesis.