Triptolide exposure triggers testicular vacuolization injury by disrupting the Sertoli cell junction and cytoskeletal organization via the AKT/mTOR signaling pathway.

BACKGROUND: Despite the known reproductive toxicity induced by triptolide (TP) exposure, the regulatory mechanism underlying testicular vacuolization injury caused by TP remains largely obscure. METHODS: Male mice were subjected to TP at doses of 15, 30, and 60 µg/kg for 35 consecutive days. Primary Sertoli cells were isolated from 20-day-old rat testes and exposed to TP at concentrations of 0, 40, 80, 160, 320, and 640 nM. A Biotin tracer assay was conducted to assess the integrity of the blood-testis barrier (BTB). Transepithelial electrical resistance (TER) assays were employed to investigate BTB function in primary Sertoli cells. Histological structures of the testes and epididymides were stained with hematoxylin and eosin (H&E). The expression and localization of relevant proteins or pathways were assessed through Western blotting or immunofluorescence staining. RESULTS: TP exposure led to dose-dependent testicular injuries, characterized by a decreased organ coefficient, reduced sperm concentration, and the formation of vacuolization damage. Furthermore, TP exposure disrupted BTB integrity by reducing the expression levels of tight junction (TJ) proteins in the testes without affecting basal ectoplasmic specialization (basal ES) proteins. Through the TER assay, we identified that a TP concentration of 160 nM was optimal for elucidating BTB function in primary Sertoli cells, correlating with reductions in TJ protein expression. Moreover, TP exposure induced changes in the distribution of the BTB and cytoskeleton-associated proteins in primary Sertoli cells. By activating the AKT/mTOR signaling pathway, TP exposure disturbed the balance between mTORC1 and mTORC2, ultimately compromising BTB integrity in Sertoli cells. CONCLUSION: This investigation sheds light on the impacts of TP exposure on testes, elucidating the mechanism by which TP exposure leads to testicular vacuolization injury and offering valuable insights into comprehending the toxic effects of TP exposure on testes.

Transcriptome Analysis of Key Genes Involved in the Initiation of Spermatogonial Stem Cell Differentiation.

PURPOSE: The purpose of this study was to screen the genes and pathways that are involved in spermatogonia stem cell (SSC) differentiation regulation during the transition from Aundiff to A1. Methods: RNA sequencing was performed to screen differentially expressed genes at 1 d and 2 d after SSC differentiation culture. KEGG pathway enrichment and GO function analysis were performed to reveal the genes and pathways related to the initiation of early SSC differentiation. RESULTS: The GO analysis showed that Rpl21, which regulates cell differentiation initiation, significantly increased after 1 day of SSC differentiation. The expressions of Fn1, Cd9, Fgf2, Itgb1, Epha2, Ctgf, Cttn, Timp2 and Fgfr1, which are related to promoting differentiation, were up-regulated after 2 days of SSC differentiation. The analysis of the KEGG pathway revealed that RNA transport is the most enriched pathway 1 day after SSC differentiation. Hspa2, which promotes the differentiation of male reproductive cells, and Cdkn2a, which participates in the cell cycle, were significantly up-regulated. The p53 pathway and MAPK pathway were the most enriched pathways 2 days after SSC differentiation. Cdkn1a, Hmga2, Thbs1 and Cdkn2a, microRNAs that promote cell differentiation, were also significantly up-regulated. CONCLUSIONS: RNA transport, the MAPK pathway and the p53 pathway may play vital roles in early SSC differentiation, and Rpl21, Fn1, Cd9, Fgf2, Itgb1, Epha2, Ctgf, Cttn, Timp2, Fgfr1, Hspa2, Cdkn2a, Cdkn1a, Hmga2 and Thbs1 are involved in the initiation of SSC differentiation. The findings of this study provide a reference for further revelations of the regulatory mechanism of SSC differentiation.

Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia-reperfusion injury: unfolding new epigenetic frontiers.

BACKGROUND: The management of myocardial ischemia-reperfusion injury (MIRI) presents continuous therapeutic challenges. NAD-dependent deacetylase Sirtuin 6 (Sirt6) plays distinct roles in various disease contexts and is hence investigated for potential therapeutic applications for MIRI. This study aimed to examine the impact of Sirt6-overexpressing exosomes derived from adipose stem cells (S-ASC-Exo) on MIRI, focusing on their influence on AIM2-pyroptosis and mitophagy processes. The sirtuin family of proteins, particularly Sirtuin 6 (Sirt6), play a pivotal role in these processes. This study aimed to explore the potential therapeutic effects of Sirt6-enriched exosomes derived from adipose stem cells (S-ASC-Exo) on regulating MIRI. RESULTS: Bioinformatic analysis revealed a significant downregulation of Sirt6 in MIRI subjected to control group, causing a consequential increase in mitophagy and pyroptosis regulator expressions. Therefore, our study revealed that Sirt6-enriched exosomes influenced the progression of MIRI through the regulation of target proteins AIM2 and GSDMD, associated with pyroptosis, and p62 and Beclin-1, related to mitophagy. The introduction of S-ASC-Exo inhibited AIM2-pyroptosis while enhancing mitophagy. Consequently, this led to a significant reduction of GSDMD cleavage and pyroptosis in endothelial cells, catalyzing a deceleration in the progression of atherosclerosis. Extensive in vivo and in vitro assays were performed to validate the expressions of these specific genes and proteins, which affirmed the dynamic modulation by Sirt6-enriched exosomes. Furthermore, treatment with S-ASC-Exo drastically ameliorated cardiac functions and limited infarct size, underlining their cardioprotective attributes. CONCLUSIONS: Our study underscores the potential therapeutic role of Sirt6-enriched exosomes in managing MIRI. We demonstrated their profound cardioprotective effect, evident in the enhanced cardiac function and attenuated tissue damage, through the strategic modulation of AIM2-pyroptosis and mitophagy. Given the intricate interplay between Sirt6 and the aforementioned processes, a comprehensive understanding of these pathways is essential to fully exploit the therapeutic potential of Sirt6. Altogether, our findings indicate the promise of Sirt6-enriched exosomes as a novel therapeutic strategy in treating ischemia-reperfusion injuries and cardiovascular diseases at large. Future research needs to underscore optimizing the balance of mitophagy during myocardial ischemia to avoid potential loss of normal myocytes.

Corrigendum to "Digital exclusion and functional dependence in older people: findings from five longitudinal cohort studies" eClinical Medicine 54 (2022) 101708.

[This corrects the article DOI: 10.1016/j.eclinm.2022.101708.].

Application of non-invasive prenatal testing to 91,280 spontaneous pregnancies and 3477 pregnancies conceived by in vitro fertilization.

BACKGROUND: Many clinical studies based on spontaneous pregnancies (SPs) have demonstrated the superiority of non-invasive prenatal testing (NIPT), and the question of whether this technology is suitable for offspring conceived by assisted reproductive technology has attracted attention. This study aimed to evaluate the application value of NIPT in screening for trisomy (T)21, T18, T13 and sex chromosome aneuploidy (SCA) in pregnant women who conceived by in vitro fertilization (IVF). RESULTS: In total, there were 804 high-risk cases [0.88% (804/91280), singleton = 795, twin = 9] in the SP group. Among the 558 invasive prenatal diagnosis (IPD) cases (singleton = 556, twin = 2), 343 (singleton = 342, twin = 1) were true positive, including 213 cases of T21, 28 of T18, 5 of T13 and 97 (singleton = 96, twin = 1) of SCA. The positive predictive values (PPVs) of T21, T18, T13, SCA and T21/T18/T13 combined in singleton pregnancy were 89.12% (213/239), 51.85% (28/54), 21.74% (5/23), 40.00% (96/240), and 77.85% (246/316), respectively, and the PPV of SCA in twin pregnancy was 100.00%. In the IVF group, IPD was performed in 19 (singleton = 16, twin = 3) of the 27 high-risk cases [0.78% (27/3477), singleton = 16, twin = 3], of which 9 (singleton = 8, twin = 1) were true positive, including 5 cases (singleton = 4, twin = 1) of T21 and 4 of SCA. The PPVs of singleton T21, SCA and T21/T18/T13 combined were 66.67% (4/6), 50.00% (4/8) and 57.14% (4/7), respectively, and the PPV of twin T21 was 100.00% (1/1). There were no significant differences in PPV among T21, SCA and T21/T18/T13 combined in singletons between the groups (89.12% vs. 66.67%, p = 0.09; 40.00% vs. 50.00%, p = 0.57; 77.85% vs. 57.14%, p = 0.20). The sensitivity and specificity were higher for singleton and twin pregnancies in the two groups. Based on follow-up results, 1 case of false negative T21 was found in the singleton SP group. Additionally, the mean foetal fraction (FF) of the IVF group was lower than that of the SP group (11.23% vs. 10.51%, p < 0.05). CONCLUSION: NIPT has high sensitivity and specificity in screening chromosomal aneuploidies in both IVF pregnancy and spontaneous pregnancy, so it is an ideal screening method for IVF pregnancy.

High-fat diet alters the radiation tolerance of female mice and the modulatory effect of melatonin.

High-fat diet (HFD) increases the risk of developing malignant tumors. Ionizing radiation (IR) is used as an adjuvant treatment in oncology. In this study, we investigated the effects of an 8-week 35% fat HFD on the tolerance to IR and the modulatory effect of melatonin (MLT). The results of lethal dose irradiation survival experiments revealed that the 8-week HFD altered the radiation tolerance of female mice and increased their radiosensitivity, whereas it had no comparable effects on males. Pre-treatment with MLT was, however, found to attenuate the radiation-induced hematopoietic damage in mice, promote intestinal structural repair after whole abdominal irradiation (WAI), and enhance the regeneration of Lgr5+ intestinal stem cells. 16S rRNA high-throughput sequencing and untargeted metabolome analyses revealed that HFD consumption and WAI sex-specifically altered the composition of intestinal microbiota and fecal metabolites and that MLT supplementation differentially modulated the composition of the intestinal microflora in mice. However, in both males and females, different bacteria were associated with the modulation of the metabolite 5-methoxytryptamine. Collectively, the findings indicate that MLT ameliorates the radiation-induced damage and sex-specifically shapes the composition of the gut microbiota and metabolites, protecting mice from the adverse side effects associated with HFD and IR.

Genetic risk, muscle strength and risk of incident major depressive disorder: results from the UK Biobank.

BACKGROUND: Genetic factors and muscle strength both contribute to the risk of major depressive disorder (MDD), but whether high muscle strength can offset the risk of MDD with different genetic risk is unknown. This study aims to examine whether a higher muscle strength is associated with lower risk of MDD regardless of genetic risk among middle-aged and older adults. METHODS: This cohort study obtained data from the UK Biobank, which includes 345,621 individuals aged 40-69 years (mean (standard deviation): 56.7 (7.99) years) without baseline MDD. Polygenic risk score for MDD was categorised as low, intermediate or high. The mean of the right- and left-hand grip strength values was used in the analysis and was divided into three categories. RESULTS: 9,753 individuals developed MDD within 2,752,461 person-years of follow-up. The multivariable adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) of MDD across increased grip strength categories were 1.00, 0.72 (0.68-0.75) and 0.56 (0.53-0.59) (P for trend <0.0001). The HRs (95% CIs) of incident MDD across the genetic risk categories were 1.00, 1.11 (1.05-1.17) and 1.20 (1.13-1.28) (P for trend <0.0001); 4.07% of individuals with a high genetic risk and low grip strength developed MDD, and 1.72% of individuals with a low genetic risk and high grip strength developed MDD, with an HR (95% CI) of 0.44 (0.39-0.50). CONCLUSIONS: Both muscle strength and genetic risk were significantly associated with incident MDD. A higher muscle strength was associated with a lower MDD risk among individuals with a high genetic risk. Improving muscle strength should be encouraged for all individuals, including individuals with high genetic risk for MDD.

Association of Thyroid-Stimulating Hormone With All-Cause Mortality: A 2-Sample Mendelian Randomization Study.

CONTEXT: Thyroid-stimulating hormone (TSH), as the most sensitive and specific marker of thyroid status, is associated with multiple health outcomes, including mortality. However, whether TSH levels are causally associated with the risk of mortality remains unclear. OBJECTIVE: This study aims to investigate the causal association between TSH levels and all-cause mortality using Mendelian randomization (MR) analyses. METHODS: MR analyses using single-nucleotide polymorphisms (SNPs) associated with TSH levels (P < 5 × 10-8) as instruments. Mortality data were obtained from the UK Biobank, including 384 344 participants who were recruited from 22 assessment centers across the UK taken between 2006 and 2010. Cox proportional hazards regression was used to estimate the association of the TSH genetic risk score (GRS) with all-cause and cause-specific mortality. RESULTS: 15 557 individuals died during a median of 9.00 years of follow-up in the UK Biobank. A total of 70 SNPs were included in the MR analysis. The main MR analyses showed that 1 SD increase in TSH was associated with a decreased risk of all-cause mortality (OR 0.972, 95% CI 0.948-0.996), which may be largely attributed to respiratory disease mortality (OR 0.881, 95% CI 0.805-0.963). The multivariable hazard ratios (HRs) (95% CI) of all-cause mortality across 3 TSH GRS categories were 1.00 (reference), 0.976 (0.940-1.014), and 0.947 (0.911-0.985), respectively (P for trend < .01). Moreover, except digestive diseases mortality, genetically predicted TSH levels were negatively associated with mortality from CVD, cancer, noncancer diseases causes, and dementia, although not statistically significant. CONCLUSION: Higher TSH levels were causally associated with lower risk of all-cause mortality, which may be largely attributed to respiratory disease mortality.

Transcriptome Analysis in High Temperature Inhibiting Spermatogonial Stem Cell Differentiation In Vitro.

As one of the factors of male infertility, high temperature induces apoptosis of differentiated spermatogenic cells, sperm DNA oxidative damage, and changes in morphology and function of Sertoli cells. Spermatogonial stem cells (SSCs) are a type of germline stem cells that maintain spermatogenesis through self-renewal and differentiation. At present, however, the effect of high temperature on SSC differentiation remains unknown. In this study, an in vitro SSC differentiation model was used to investigate the effect of heat stress treatment on SSC differentiation, and RNA sequencing (RNA-seq) was used to enrich the key genes and pathways in high temperature inhibiting SSC differentiation. Results show that 2 days of 37 °C or 43 °C (30 min per day) heat stress treatment significantly inhibited SSC differentiation. The differentiation-related genes c-kit, stra8, Rec8, Sycp3, and Ovol1 were down-regulated after 2 and 4 days of heat stress at 37 °C. The transcriptome of SSCs was significantly differentially expressed on days 2 and 4 after heat stress treatment at 37 °C. In total, 1660 and 7252 differentially expressed genes (DEGs) were identified by RNA-seq in SSCs treated with heat stress at 37 °C for 2 and 4 days, respectively. KEGG pathway analysis showed that p53, ribosome, and carbon metabolism signaling pathways promoting stem cell differentiation were significantly enriched after heat stress treatment at 37 °C. In conclusion, 37 °C significantly inhibited SSC differentiation, and p53, ribosome, and carbon metabolism signaling pathways were involved in this differentiation inhibition process. The results of this study provide a reference for further investigation into the mechanism by which high temperature inhibits SSC differentiation.

Digital exclusion and functional dependence in older people: Findings from five longitudinal cohort studies.

Background: Older people are more likely to be excluded from the digital world, and this has been linked to poor health outcomes. The extent and direction of the influence of digital exclusion on functional dependency is, however, not well understood. We aimed to investigate the association between digital exclusion and functional dependency among older adults from high-income countries (HICs) and low- and middle-income countries (LMICs). Methods: In this multicohort study, we pooled individual-level data from five longitudinal cohort studies that included nationally representative samples of older adults across 23 countries, including the Health and Retirement Study (HRS), the English Longitudinal Study of Aging (ELSA), the Survey of Health, Ageing and Retirement in Europe (SHARE), the China Health and Retirement Longitudinal Study (CHARLS), and the Mexican Health and Aging Study (MHAS). The digital exclusion was recorded as an absence from internet use by self-reported. We assessed basic activities of daily living (BADL) and instrumental activities of daily living (IADL), and we used interval-of-need methods to categorize the functional dependency. We applied generalized estimating equations models fitting Poisson model to investigate the association of digital exclusion with difficulties in BADL or IADL and functional dependency, adjusting for the causal-directed-acyclic-graph (DAG) minimal sufficient adjustment set (MSAS), including gender, age level, labour force status, education, household wealth level, marital status, and co-residence with children. Findings: We included 108,621 participants recruited between 2010 and 2018 with a median follow-up of 3 phrases. Digital exclusion in older adults varied across countries, ranging from 23.8% in Denmark (SHARE) to 96.9% in China (CHARLS). According to the crude model, digital exclusion was significantly associated with functional dependency. In the MSAS-adjusted model, those associations remained statistically significant: HRS (incidence rate ratio [IRR] = 1.40, 95% confidence interval [CI] 1.34-1.48 for BADL; 1.71 [1.61-1.82] for IADL), ELSA (1.31 [1.22-1.40] in BADL and 1.37 [1.28-1.46] in IADL), SHARE (1.69 [1.61-1.78] in BADL and 1.70 [1.63-1.78] in IADL), CHARLS (2.15 [1.73-2.67] in BADL and 2.59 [2.06-3.25] in IADL), and MHAS (1.15 [1.09-1.21] in BADL and 1.17 [1.09-1.25] in IADL). In the subgroup analyses, the associations were more pronounced in the oldest-old (aged ≥ 80 years old). Interpretation: There is a substantial proportion of older adults who are excluded from the Internet, especially those in LMIC. Older people excluded from the Internet regardless of whether they live in HICs or LMICs are more likely to develop functional dependency. It should be made a priority to remove barriers to Internet access in order to assist older people in maintaining their independence and, consequently, to reduce the care burden associated with the ageing population worldwide. Funding: The National Natural Science Foundation of China (No. 71904004).

Acrylamide fragment inhibitors that induce unprecedented conformational distortions in enterovirus 71 3C and SARS-CoV-2 main protease.

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional proteins. Many of these proteases exhibit a similar fold and contain an essential catalytic cysteine, offering the opportunity to inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that target the active site cysteine of the 3C protease (3Cpro) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we re-purpose these hits towards the main protease (Mpro) of SARS-CoV-2 which shares the 3C-like fold and a similar active site. The hit fragments covalently link to the catalytic cysteine of Mpro to inhibit its activity. We demonstrate that targeting the active site cysteine of Mpro can have profound allosteric effects, distorting secondary structures to disrupt the active dimeric unit.

High precision angular displacement measurement based on self-correcting error compensation of three image sensors.

As the feedback link of a numerical control system, the measurement accuracy of absolute angular displacement measurements directly affects the control performance of a numerical control system. In previous research, angular displacement measurements based on dual image sensors can achieve higher measurement performance. However, the elimination of harmonic error by the dual image sensor is still limited. For this reason, this paper proposes an image-type angular displacement measurement method based on self-correction error compensation of three image sensors. First, the mathematical model of harmonic error is established, and the shortcomings of using dual image sensors to compensate the error are analyzed. Then, a high precision angular displacement measurement method based on three image sensors is proposed. Finally, the self-correction error compensation method of three image sensors is applied to the angular displacement measurement system, and the measurement performance is verified. The experimental results show that a measurement accuracy of 1.76'' can be achieved on the circular grating with a diameter of 96 mm. In contrast, the dual image sensor can only achieve a measurement accuracy of 2.88''. It is concluded that the odd number of image sensors can achieve higher measurement accuracy than the even number. This research lays a foundation for the realization of high precision image angular displacement measurement.

High-precision displacement measurement algorithm based on a depth fusion of grating projection pattern.

Displacement measurement based on an image recognition algorithm has more advantages in the field of displacement measurement. Due to the uncertainty of image location, the accuracy of the displacement measurement algorithm studied in the previous stage is limited. To improve the accuracy of image-type displacement measurement, a high-precision displacement measurement algorithm based on depth fusion of the grating projection pattern is proposed. First, a line-scan image sensor and parallel light source are placed on both sides of the calibration grating. The marking pattern on the calibration grating is projected onto the image sensor through illumination of the parallel light source to realize the projection imaging. Then, the centroid algorithm is used to calculate the centroid of each line in the collected image, and the mean value of the centroid group is determined. Finally, a linear function is used to fit multiple centroids to calculate the endpoints of the subdivision region, and the subdivision operation is carried out according to a ratio algorithm. To test the performance of the proposed algorithm, a linear displacement measurement device with a 250 mm range and an angular displacement measurement device with a 100 mm diameter grating are both used for experiments. After testing, the linear measurement accuracy of the proposed algorithm is improved from 4.63 to 1.26 µm, and the angular displacement measurement accuracy is enhanced from 8.87 to 2.88''. The research in this paper provides a theoretical basis for high-performance displacement measurement.

Willingness to accept COVID-19 vaccine among the elderly and the chronic disease population in China.

A cross-sectional field survey was conducted from November 2020 to January 2021 among 7259 participants to investigate the public perception, willingness, and information sources for COVID-19 vaccination, with the focus on the elderly and non-communicable chronic disease (NCD) population. Multiple logistic regressions were performed to identify associated factors of the vaccination willingness. The willingness rate of the elderly to accept the future COVID-19 vaccine (79.08%) was lower than that of the adults aged 18-59 (84.75%). The multiple analysis didn't identify significant relationship between NCD status and the vaccination intention. The main reasons for vaccine hesitancy by the public were: concern for vaccine safety, low infection risk, waiting and seeing others getting vaccinated, concern of vaccine effectiveness and price. Their relative importance differed between adults aged 18-59 and the elderly, and between adults aged 18-59 with or without NCD. Perception for vaccination importance, vaccine confidence, and trust in health workers were significant predictors of the vaccination intention in both age groups. The elderly who perceived high infection risk or had trust in governments were more likely to accept the vaccine. Compared with the adults aged 18-59, the elderly used fewer sources for COVID-19 vaccination information and more trusted in traditional media and family, relatives, and friends for getting vaccination recommendations. To promote vaccine uptake, the vaccination campaigns require comprehensive interventions to improve vaccination attitude, vaccine accessibility and affordability, and tailor strategies to address specific concerns among different population groups and conducted via their trusted sources, especially for the elderly.

Women's Empowerment and Children's Complete Vaccination in the Democratic Republic of the Congo: A Cross-Sectional Analysis.

(1) Background: The empowerment of women contributes to better child health and wellness. This study aimed to examine the association between women's empowerment and complete vaccination of children, as recommended in the National Expanded Program on Immunization (EPI) in the Democratic Republic of the Congo (DRC). (2) Methods: In this cross-sectional study, a principal component analysis (PCA) was conducted on data from the Multiple-Indicator Cluster Survey 6 (MICS-6) to determine the dimensions of women's empowerment. Logistic regression analysis was used to assess the association between women's empowerment and complete vaccination of children stratified by household wealth. In total, 3524 women with children aged 12-23 months were included in the study. (3) Results: Women's empowerment was defined by three dimensions, namely intrinsic agency, enabling resources, and social independence. Children of women with high levels of empowerment had higher odds of complete vaccination, with values of 1.63 (p = 0.002) and 1.59 (p = 0.012) for intrinsic agency and enabling resources of the empowerment, respectively, compared to the children of women with low levels of empowerment; however, social independence failed to be associated with the vaccination status of children. After stratification by household wealth, the OR of complete vaccination was higher in women from middle-income households with high levels of intrinsic agency (OR: 2.35, p = 0.021) compared to women from poor households with high levels of intrinsic agency (OR: 1.92, p = 0.004). (4) Conclusions: Higher levels of women's empowerment, especially intrinsic agency and enabling resources, were associated with complete vaccination in children in the DRC. Household wealth status influenced the associations. The empowerment of women is crucial in promoting the complete vaccination of children and providing equal access to vaccines.

Orthogonal pre-use and post-use efficiency testing for single-use anion exchange chromatography.

Three efficiency tests for single-use AEX chromatography devices have been developed and applied to six capsule formats of a new, salt tolerant, single-use AEX product. All the tests have been designed to be performed with simple equipment and common reagents. By performing each of the three tests on undamaged capsules and capsules intentionally damaged with small defects, in tandem with Phi-X174 challenges in a high-salt buffer, relationships between test results and viral clearance have been obtained. A pre-use pressure-based installation verification test is simply performed during equilibration of the device and effective at identifying gross bypass defects, for example, due to internal seal breakage. Passing outcomes of a post-use installation validation bubble point test are associated with ≥ 5 log reduction value (LRV) of viral clearance. A new, non-destructive, pre-use AEX capacity test involves challenging the device with chloride ions and is orthogonal to the other two tests in that it can detect chemical defects, as well as mechanical ones. Passing outcomes of this test correspond to > 2 LRV viral clearance and provide in situ assurance of the expected AEX dynamic capacity prior to use. Selection of a pair of pre-use and post-use tests can provide robust risk reduction with respect to viral clearance by single-use AEX devices in biopharmaceutical purifications.

Performance of non-invasive prenatal testing for foetal chromosomal abnormalities in 1048 twin pregnancies.

OBJECTIVE: To investigate the clinical value of non-invasive prenatal testing (NIPT) to screen for chromosomal abnormalities in twin pregnancies and to provide further data on NIPT manifestations in twin pregnancies. MATERIALS AND METHODS: In a 4-year period, 1048 women with twin pregnancies were voluntarily prospectively tested by NIPT to screen for chromosomal abnormalities by sequencing cell-free foetal DNA (cffDNA) in maternal plasma. Positive NIPT results were confirmed by karyotyping, while negative results were followed up 42 days after delivery. RESULTS: Thirteen women had positive NIPT results as follows: 2 cases of trisomy 21 (T21), 1 of trisomy 18 (T18), 7 of sex chromosome aneuploidy (SCA), 1 of microdeletion, and 2 of microduplication. Of these 13 cases, 2 were true-positive cases confirmed by foetal karyotype analysis, namely, 1 case of T21 and 1 of microdeletion. Furthermore, the remaining 11 high-risk pregnant women were confirmed as false positive by foetal karyotyping. Thus, the combined positive predictive value (PPV) of NIPT screening for chromosomal abnormalities in twin pregnancies was 15.4% (2/13). There were no false-negative case via our follow-up results. CONCLUSION: Safe and rapid NIPT has a certain clinical application value; however, the PPV is limited, and the screening efficiency is not stable. Careful use should be made in the screening of chromosomal abnormalities in twin pregnancies.

The Changing Acceptance of COVID-19 Vaccination in Different Epidemic Phases in China: A Longitudinal Study.

COVID-19 vaccines have been conditionally used in a few countries, including China since December 2020. The present study aimed to examine whether the acceptance of COVID-19 vaccination changed in different COVID-19 epidemic phases in China. Two consecutive surveys were conducted among Chinese adults in March (n = 2058) (severe epidemic phase) and November-December (n = 2013) (well-contained phase, right before the COVID-19 vaccine was conditionally approved) 2020, and 791 respondents were longitudinally followed-up. The attitude, acceptance, and preferences for future COVID-19 vaccination were compared between two epidemic phases. Multivariate logistic regression was used to identify influencing factors of acceptance. Among the 791 respondents longitudinally followed, 91.9% in March and 88.6% of them in November-December 2020 would like to get COVID-19 vaccination in China. In March 58.3% wished to get vaccinated immediately, but the proportion declined to 23.0% in November-December 2020, because more respondents wanted to delay vaccination until the vaccine's safety was confirmed. Similar results were found by comparing all respondents from the two cross-sectional surveys in different epidemic phases. The risk perception, attitude for the importance of vaccination against COVID-19, vaccination history, valuing doctor's recommendations, vaccination convenience, or vaccine price in decision-making had impacts on respondents' intention for immediate vaccination. The public acceptance for COVID-19 vaccination in China sustained at a high level in different COVID-19 epidemic phases. However, the intention of immediate vaccination declined substantially due to concerns about the vaccine's safety. Information about vaccination safety from authoritative sources, doctor's recommendations, and vaccination convenience were important in addressing vaccine hesitancy and promoting successful herd immunity for the general population in China.

Noninvasive prenatal testing for assessing foetal sex chromosome aneuploidy: a retrospective study of 45,773 cases.

OBJECTIVE: To assess the positive predictive value (PPV) of noninvasive prenatal testing (NIPT) as a screening test for sex chromosome aneuploidy (SCA) with different maternal characteristics and prenatal decisions in positive cases. MATERIALS AND METHODS: We retrospectively analysed 45,773 singleton pregnancies with different characteristics that were subjected to NIPT in the Maternity and Child Health Hospital of Anhui Province. The results were validated by karyotyping. Clinical data, diagnostic results, and data on pregnancy outcomes were collected. RESULTS: In total, 314 cases were SCA positive by NIPT; among those, 143 underwent invasive prenatal diagnostic testing, and 58 were true-positive. Overall, the PPVs for 45,X, 47,XXX, 47,XXY and 47,XYY were 12.5%, 51.72%, 66.67% and 83.33%, respectively. Interestingly, when only pregnant women of advanced maternal age (AMA) were screened, the PPVs for 45,X, 47,XXX, 47,XXY and 47,XYY were 23.81%, 53.33%, 78.95%, and 66.67%, respectively. The frequency of SCA was significantly higher in the AMA group than in the non-AMA group. The frequencies of 47,XXX and 47,XXY were significantly correlated with maternal age. CONCLUSION: NIPT performed better in predicting sex chromosome trisomies than monosomy X, and patients with 45,X positive foetuses were more eager to terminate pregnancy than those with 47,XXX and 47,XYY. AMA may be a risk factor of having a foetus with SCA. Our findings may assist in genetic counselling of AMA pregnant women. Our pre- and posttest counselling are essential for familiarizing pregnant women with the benefits and limitations of NIPT, which may ease their anxiety and enable them to make informed choices for further diagnosis and pregnancy decisions.

Anti-stain algorithm of angular displacement based on a single image sensor.

The displacement measuring technique is prone to failure within the industrial environment due to the influence of dust, oil, and other contaminants that stain the equipment. There is urgent demand for new anti-stain techniques. In today's image angular displacement measurement technology, the pixel array is used instead of the traditional photoelectric conversion element; this creates room for anti-stain improvement based on the image processing components. Based on a previous study on image-type angular displacement measurement technology, a single head image-type anti-stain algorithm is proposed in this paper that can remove the interference of small stains and ensure correct measurement value outputs. The influence of the stain on the calibration grating is first assessed based on the principle of image angular displacement measurement technology. An anti-stain algorithm based on the metal grating and multi-line fusion is proposed accordingly. The proposed algorithm is then tested on a circular grating with 38 mm diameter and ${{2}^{N}}\; = \;{256}$2N=256 lines in the circle. The results show that angle measurement output accuracy can be guaranteed when the number of lines covered by the stains is less than half of the coding-bits. This work may provide a technical basis for enhancing stain resistance in high-performance displacement measurement technology.