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Despite the longstanding evidence on the effect of air pollutants on preterm birth (PTB), few studies have focused on its subtypes, including spontaneous preterm birth (sPTB) and medically indicated preterm birth (miPTB). Most studies evaluated only the short-term or long-term effects of particulate matter (PM) on PTB. Thus, we designed this study, based on a cohort of 179,385 women, to evaluate both short- and long-term effects of PM with diameters ≤2.5 μm and ≤10 μm (PM 2.5 and PM 10 ) on PTB, sPTB and miPTB in Shanghai. Generalized additive models (GAMs) were applied to evaluate short-term effects. Lagged effects were identified using different lag structures. Exposure-response correlation curves were plotted using GAMs after adjustment for confounders. ORs and 95% CIs were calculated using logistic regression to estimate the long-term effect after adjustment for confounders. There was 5.67%, 3.70% and 1.98% daily incidence of PTB, sPTB, and miPTB on average. Every 10 μg/m 3 increase in PM 2.5 and PM 10 was positively associated with PTB and sPTB at lag 2 day. The exposure-response curves (lag 2 day) indicated a rapid increase in sPTB for PM 2.5 and a linear increase for PM 10 , in PTB for PM 2.5 and PM 10 at concentrations over 100 μg/m 3 . Regarding long-term exposure, positive associations were found between 10 μg/m 3 increases in PM 2.5 and PM 10 in 3rd trimester and greater odds of sPTB (aOR: 1.042, 95% CI: 1.018-1.065, and 1.018, 95% CI:1.002-1.034), and during the 3 months before conception and miPTB (aOR: 1.023, 95% CI: 1.003-1.042, and 1.017, 95% CI: 1.000-1.036). Acute exposure to PM 2.5 and PM 10 at lag 2 day and chronic exposure in 3rd trimester was significantly associated with sPTB, while miPTB was related to chronic exposure during the 3 months before pregnancy. These findings indicate that susceptibility windows of PM exposure can be influenced by different underlying etiologies of PTB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: GKRS is an effective treatment for smaller intracranial tumors with a high control rate and low risk of complications. Target delineation in medical MR images is essential in the planning of GKRS and follow-up. A deep learning-based algorithm can effectively segment the targets from medical images and has been widely explored. However, state-of-the-art deep learning-based target delineation uses fixed sizes, and the isotropic voxel size may not be suitable for stereotactic MR images which use different anisotropic voxel sizes and numbers of slices according to the lesion size and location for clinical GKRS planning. This study developed an automatic deep learning-based segmentation scheme for stereotactic MR images., Methods: We retrospectively collected stereotactic MR images from 506 patients with VS, 1,069 patients with meningioma and 574 patients with BM who had been treated using GKRS; the lesion contours and individual T1W+C and T2W MR images were extracted from the GammaPlan system. The three-dimensional patching-based training strategy and dual-pathway architecture were used to manage inconsistent FOVs and anisotropic voxel size. Furthermore, we used two-parametric MR image as training input to segment the regions with different image characteristics (e.g., cystic lesions) effectively., Results: Our results for VS and BM demonstrated that the model trained using two-parametric MR images significantly outperformed the model trained using single-parametric images with median Dice coefficients (0.91, 0.05 versus 0.90, 0.06, and 0.82, 0.23 versus 0.78, 0.34, respectively), whereas predicted delineations in meningiomas using the dual-pathway model were dominated by single-parametric images (median Dice coefficients 0.83, 0.17 versus 0.84, 0.22). Finally, we combined three data sets to train the models, achieving the comparable or even higher testing median Dice (VS: 0.91, 0.07; meningioma: 0.83, 0.22; BM: 0.84, 0.23) in three diseases while using two-parametric as input., Conclusions: Our proposed deep learning-based tumor segmentation scheme was successfully applied to multiple types of intracranial tumor (VS, meningioma and BM) undergoing GKRS and for segmenting the tumor effectively from stereotactic MR image volumes for use in GKRS planning., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Characteristics of the neighbourhood environment, including the built and natural environment, area-level socio-economic status (SES) and air pollution, have been linked to cognitive health. However, most studies have focused on single neighbourhood characteristics and have not considered the extent to which the effects of environmental factors may interact. We examined the associations of measures of the neighbourhood built and natural environment, area-level SES and traffic-related air pollution (TRAP) with two cognitive function domains (memory and processing speed), and the extent to which area-level SES and TRAP moderated the associations. We used cross-sectional data from the AusDiab3 study, an Australian cohort study of adults (mean age: 61 years) in 2011-12 (N = 4141) for which geocoded residential addresses were available. Spatial data were used to create composite indices of built environment complexity (population density, intersection density, non-commercial land use mix, commercial land use) and natural environment (parkland and blue spaces). Area-level SES was obtained from national census indices and TRAP was based on estimates of annual average levels of nitrogen dioxide (NO 2 ). Confounder-adjusted generalised additive mixed models were used to estimate the independent associations of the environmental measures with cognitive function and the moderating effects of area-level SES and TRAP. The positive associations between built environment complexity and memory were stronger in those living in areas with higher SES and lower NO 2 concentrations. A positive association between the natural environment and memory was found only in those living in areas with lower NO 2 concentrations and average or below-average SES. Built environment complexity and the natural environment were positively related to processing speed. Complex urban environments and access to nature may benefit cognitive health in ageing populations. For higher-order cognitive abilities, such as memory, these positive effects may be stronger in areas with lower levels of TRAP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Rapid evolution of artificial intelligence (AI) prompted its wide application in healthcare systems. Stereotactic radiosurgery served as a good candidate for AI model development and achieved encouraging result in recent years. This article aimed at demonstrating current AI application in radiosurgery., Methods: Literatures published in PubMed during 2010-2022, discussing AI application in stereotactic radiosurgery were reviewed., Results: AI algorithms, especially machine learning/deep learning models, have been administered to different aspect of stereotactic radiosurgery. Spontaneous tumor detection and automated lesion delineation or segmentation were two of the promising application, which could be further extended to longitudinal treatment follow-up. Outcome prediction utilized machine learning algorithms with radiomic-based analysis was another well-established application., Conclusions: Stereotactic radiosurgery has taken a lead role in AI development. Current achievement, limitation, and further investigation was summarized in this article., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mechanical products are becoming more diversified with the continuous development of precision processing and materials technologies. The friction force generated by the O-ring seal in a hydraulic cylinder was once considered redundant. However, its utilization has recently been proposed. The hardness of the O-ring and the inner diameter of its groove directly affect the normal pressure between the O-ring and the inner wall of the cylinder, thereby affecting the friction behavior. In order to explore this friction behavior, a strain-based friction force measurement system is developed in this study, and the steady-state and dynamic friction values under different working conditions are studied and discussed in depth. This research on the friction behavior in the cylinder provides a theoretical basis for more convenient design and utilization of the friction force generated between the O-ring and the inner wall of the cylinder., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Qin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a first-line therapy for non-small cell lung cancer (NSCLC) with EGFR mutations. Approximately half of the patients with EGFR-mutated NSCLC are treated with EGFR-TKIs and develop disease progression within 1 year. Therefore, the early prediction of tumor progression in patients who receive EGFR-TKIs can facilitate patient management and development of treatment strategies. We proposed a deep learning approach based on both quantitative computed tomography (CT) characteristics and clinical data to predict progression-free survival (PFS) in patients with advanced NSCLC after EGFR-TKI treatment., Methods: A total of 593 radiomic features were extracted from pretreatment chest CT images. The DeepSurv models for the progression risk stratification of EGFR-TKI treatment were proposed based on CT radiomic and clinical features from 270 stage IIIB-IV EGFR-mutant NSCLC patients. Time-dependent PFS predictions at 3, 12, 18, and 24 months and estimated personalized PFS curves were calculated using the DeepSurv models., Results: The model combining clinical and radiomic features demonstrated better prediction performance than the clinical model. The model achieving areas under the curve of 0.76, 0.77, 0.76, and 0.86 can predict PFS at 3, 12, 18, and 24 months, respectively. The personalized PFS curves showed significant differences (p < 0.003) between groups with good (PFS > median) and poor (PFS < median) tumor control., Conclusions: The DeepSurv models provided reliable multi-time-point PFS predictions for EGFR-TKI treatment. The personalized PFS curves can help make accurate and individualized predictions of tumor progression. The proposed deep learning approach holds promise for improving the pre-TKI personalized management of patients with EGFR-mutated NSCLC., (© 2023. The Author(s).)

A series of π-extended salophen-type Schiff-base zinc(ii) complexes, e.g. , zinc-salophen complexes (ZSC), were investigated toward potential applications for dye-sensitized solar cells. The ZSC dyes adopt linear-, X-, or π-shaped geometries either with the functionalization of 1 donor/1 acceptor or 2 donors/2 acceptors to achieve a push-pull type molecular structure. The frontier molecular orbitals, light-harvesting properties as well as charge transfer characters against regio-specific substitution of donor/acceptor groups were studied by using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results reveal that all ZSC dyes of D-ZnS-π-A geometry (where D, S, and A denote to donor, salophen ligand, and acceptor, respectively) exhibit relatively lower HOMO energy compared to the structurally resembled porphyrin dye YD2- o -C8. Natural transition orbital (NTO) and electron-hole separation (EHS) approaches clearly differentiate the linear type YD-series dyes from CL-, AJ1-, and AJ2-series dyes because of poor charge transfer (CT) properties. In contrast, the π-shaped AJ2-series and X-shaped AJ1-series dyes outperform the others in a manner of stronger CT characteristics, broadened UV-vis absorption as well as tunable bandgap simply via substitution of p -ethynylbenzoic acids (EBAs) and arylamine donors at salophen 7,8- and 2,3,12,13-positions, respectively. Both EHS and calculated exciton binding energies suggest the strength of CT character for ZSC dyes with an amino donor in the trend TPA > AN > DPA. This work has provided clear illustration toward molecular design of efficient dyes featuring a zinc-salophen backbone., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

The blocking of programmed death-ligand 1 (PD-L1) in tumor cells represents a powerful strategy in cancer immunotherapy. Using viral vectors to deliver the cargo for inactivating the PD-L1 gene could be associated with host cell genotoxicity and concomitant immune attack. To develop an alternative safe gene delivery method, we designed a unique combination for miRNA34a delivery using a transgene carrier in the form of iron oxide magnetic nanoparticles (IONPs) via magnetofection to downregulate PD-L1 expression in cancer cells. We synthesized IONPs of multiple shapes (IONRs (iron oxide nanorods), IONSs (iron oxide nanospheres), and ITOHs (iron oxide truncated octahedrons)), surface-functionalized with polyethyleneimine (PEI) using the ligand exchange method, as gene delivery systems. Under the guidance of an external magnetic field, PEI@IONPs loaded with plasmid DNA (DNA/PEI@IONPs) encoding GFP showed high transfection efficiency at different weight ratios and time points in A549 and MDA-MB-231 cells. Additionally, the DNA/PEI@IONPs with miRNA34a inserts under a static magnetic field resulted in significant knockdown of the PD-L1 gene, as demonstrated via immunoblotting of the PD-L1 protein. Among the three shapes of IONPs, IONRs showed the highest PD-L1 knockdown efficiency. The genetic expression of miRNA34a was also studied using qPCR and it showed high expression of miRNA in cells treated with PEI@IONRs. Flow cytometry and a live/dead assay confirmed apoptosis after transfection with miRNA34a. To conclude, in this paper, a promising transgene carrier with low cost, negligible cytotoxicity, and high transfection efficiency has been successfully established for miRNA gene delivery in the context of cancer immunotherapy.

Short videos are very popular among students, but the immersive nature of the software makes them prone to problematic use and even addiction. Internet addiction, including short-video problematic use, has been a hot topic in recent years due to the COVID-19 epidemic. However, there are few empirical studies that have explored the effects of short-video problematic use on students. Thus, vocational colleges in China were recruited to participate in this study. There were 1089 effective participants, with a valid recall rate of 90.8%. This included 466 male students (42.8%) and 623 female students (57.2%), with a mean age of 19.19 years (standard deviation of 1.07 years). Five hypotheses were proposed and validated by structural equation modeling within the framework of ecological systems theory and engagement theory to explore the association of short-video problematic use, three types of learning engagement, and perceived learning ineffectiveness. Research findings showed that: (1) short-video problematic use has a negative effect on behavioral engagement; (2) behavioral engagement has a positive effect on both emotional and cognitive engagement; and (3) emotional and cognitive engagement have a negative effect on perceived learning ineffectiveness. According to the results, it can be seen that short-video problematic use has a detrimental effect on students' learning experiences, so teachers and parents need to pay attention to the negative effects of excessive use among students.

Cytoadherence of Trichomonas vaginalis to human vaginal epithelial cells (hVECs) was previously shown to involve surface lipoglycans and several reputed adhesins on the parasite. Herein, we report some new observations on the host-parasite interactions of adherent versus nonadherent T. vaginalis isolates to hVECs. The binding of the TH17 adherent isolate to hVECs exhibited an initial discrete phase followed by an aggregation phase inhibited by lactose. T. vaginalis infection immediately induced surface expression of galectin-1 and -3, with extracellular amounts in the spent medium initially decreasing and then increasing thereafter over the next 60 min. Extracellular galectin-1 and -3 were detected on the parasite surface but only the TH17 adherent isolate could uptake galectin-3 via the lysosomes. Only the adherent isolate could morphologically transform from the round-up flagellate with numerous transient protrusions into a flat amoeboid form on contact with the solid surface. Cytochalasin D challenge revealed that actin organization was essential to parasite morphogenesis and cytoadherence. Real-time microscopy showed that parasite exploring and anchoring on hVECs via the axostyle may be required for initial cytoadherence. Together, the parasite cytoskeleton behaviors may collaborate with cell surface adhesion molecules for cytoadherence. The nonadherent isolate migrated faster than the adherent isolate, with motility transiently increasing in the presence of hVECs. Meanwhile, differential histone acetylation was detected between the two isolates. Also, TH17 without Mycoplasma symbiosis suggests that symbiont might not determine TH17 innate cytoadherence. Our findings regarding distinctive host-parasite interactions of the isolates may provide novel insights into T. vaginalis infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hsu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mild cognitive impairment (MCI) is widely regarded to be the intermediate stage to Alzheimer's disease. Cerebral morphological alteration in cortical subregions can provide an accurate predictor for early recognition of MCI. Thirty patients with MCI and thirty healthy control subjects participated in this study. The Desikan-Killiany cortical atlas was applied to segment participants' cerebral cortex into 68 subregions. A complexity measure termed fractal dimension (FD) was applied to assess morphological changes in cortical subregions of participants. The MCI group revealed significantly decreased FD values in the bilateral temporal lobes, right parietal lobe including the medial temporal, fusiform, para hippocampal, and also the orbitofrontal lobes. We further proposed a novel FD-based brain structural network to compare network parameters, including intra- and inter-lobular connectivity between groups. The control group had five modules, and the MCI group had six modules in their brain networks. The MCI group demonstrated shrinkage of modular sizes with fewer components integrated, and significantly decreased global modularity in the brain network. The MCI group had lower intra- and inter-lobular connectivity in all lobes. Between cerebral lobes, the MCI patients may maintain nodal connections between both hemispheres to reduce connectivity loss in the lateral hemispheres. The method and results presented in this study could be a suitable tool for early detection of MCI.

Background/purpose: In the warm gutta-percha technique, soft-type and regular-type gutta-percha are using for backfilling thermoplasticized injection system. However, there are limited reports about the properties of these backfilling gutta-percha. This study aimed to analyze and compare the composition, thermal behavior and compact force of two types of backfilling gutta-percha., Materials and Methods: Soft-type and regular-type backfilling gutta-percha (B&L BioTech, Fairfax, VA, USA) were investigated. The inorganic and organic fractions of these gutta-perchas were separated by quantitative chemical analysis (n = 6). Their composition was analyzed using energy dispersive spectroscopy. Thermal behavior in response to temperature variations was analyzed using differential scanning calorimetry. Additionally, a compaction model was used to investigate the relation between compaction force and temperature (n = 10)., Results: The soft-type contained more gutta-percha (3.69-5.85%), carbon ratio (38.96-48.52%) and less inorganic substance (86.51-90.45%), zinc ratio (29.36-35.67%). The composition ratio of two types gutta-percha were statistically significant different ( P < 0.05). There were three phase transitions of the soft-type gutta-percha which started at 39.84 °C, 49.32 °C and 54.15 °C while the two phase transitions of the regular-type gutta-percha started at 40.48 °C and 53.45 °C. The glass transition temperature of the regular-type gutta-percha (44.24 °C) was higher than that of the soft-type gutta-percha (40.66 °C). Under various setting temperature, the higher compaction force in the regular-type gutta-percha was required ( P < 0.05)., Conclusion: The different components in gutta-percha contribute to its differences in thermal behavior. The soft-type had a higher proportion of gutta-percha and lower ZnO which makes the fluidity better than the regular-type., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Objective: This study investigated the efficacy of extracorporeal shock wave therapy as well as the optimal intervention timing for extracorporeal shock wave therapy for patients with spasticity after stroke., Design: A search of randomized controlled trials was conducted in different electronic databases. We performed a meta-analysis to measure the effect of extracorporeal shock wave therapy versus sham interventions on spasticity and limb functionality. The meta-regression analysis was performed to determine the adequate intervention timing of extracorporeal shock wave therapy. The follow-up period of the outcomes was divided into the short (<2 wks), mid (>2 wks and ≤4 wks), and long (>4 wks and ≤3 mos) terms., Results: Thirteen studies with 677 participants were evaluated. Spasticity significantly improved throughout the follow-up duration. Limb functionality significantly improved in the short-term follow-up period. The meta-regression analysis showed that patients with stroke duration less than 45 mos may be benefited from extracorporeal shock wave therapy in improving limb function in all follow-up periods., Conclusions: Extracorporeal shock wave therapy is an effective method for reducing spasticity in patients with stroke, and the effect could be maintained for up to 3 mos. Its effects on limb functionality could persist for at least 2 wks. Patients who had stroke for less than 45 mos may have significant benefit from extracorporeal shock wave therapy in all follow-up periods., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine whether multivariate pattern regression analysis based on gray matter (GM) images constrained to the sensorimotor network could accurately predict trigeminal heat pain sensitivity in healthy individuals., Background: Prediction of individual pain sensitivity is of clinical relevance as high pain sensitivity is associated with increased risks of postoperative pain, pain chronification, and a poor treatment response. However, as pain is a subjective experience accurate identification of such individuals can be difficult. GM structure of sensorimotor regions have been shown to vary with pain sensitivity. It is unclear whether GM structure within these regions can be used to predict pain sensitivity., Methods: In this cross-sectional study, structural magnetic resonance images and pain thresholds in response to contact heat stimulation of the left supraorbital area were obtained from 79 healthy participants. Voxel-based morphometry was used to extract segmented and normalized GM images. These were then constrained to a mask encompassing the functionally defined resting-state sensorimotor network. The masked images and pain thresholds entered a multivariate relevance vector regression analysis for quantitative prediction of the individual pain thresholds. The correspondence between predicted and actual pain thresholds was indexed by the Pearson correlation coefficient (r) and the mean squared error (MSE). The generalizability of the model was assessed by 10-fold and 5-fold cross-validation. Non-parametric permutation tests were used to estimate significance levels., Results: Trigeminal heat pain sensitivity could be predicted from GM structure within the sensorimotor network with significant accuracy (10-fold: r = 0.53, p < 0.001, MSE = 10.32, p = 0.001; 5-fold: r = 0.46, p = 0.001, MSE = 10.54, p < 0.001). The resulting multivariate weight maps revealed that accurate prediction relied on multiple widespread regions within the sensorimotor network., Conclusion: A multivariate pattern of GM structure within the sensorimotor network could be used to make accurate predictions about trigeminal heat pain sensitivity at the individual level in healthy participants. Widespread regions within the sensorimotor network contributed to the predictive model., (© 2022 American Headache Society.)

Background/objective: The present study investigated the impact of splenomegaly on the treatment outcomes of blunt splenic injury patients., Methods: All blunt splenic injury patients were enrolled between 2010 and 2018. The exclusion criteria were age less than 18 years, missing data, and splenectomy performed at another hospital. The patients were divided into two groups based on the presence of splenomegaly, defined as a spleen length over 9.76 cm on axial computed tomography. The primary outcome was the need for hemostatic interventions., Results: A total of 535 patients were included. Patients with splenomegaly had more high-grade splenic injuries (p = 0.007). Hemostatic treatments (p < 0.001) and transarterial embolization (p = 0.003) were more frequently required for patients with splenomegaly. Multivariate analysis showed that male sex (p = 0.023), more packed red blood cell transfusions (p = 0.001), splenomegaly (p = 0.019) and grade 3-5 splenic injury (p < 0.001) were predictors of hemostatic treatment. The failure rate of transarterial embolization was not significantly different between the two groups (p = 0.180). The sensitivity and specificity for splenomegaly in predicting hemostatic procedures were 48.8% and 66.5%, respectively. The positive and negative predictive values were 62.8% and 52.9%, respectively. The overall mortality rate was 3.7%., Conclusion: Splenomegaly is an independent predictor for the requirement of hemostatic treatments in blunt splenic injury patients, especially transarterial embolization. Transarterial embolization is as effective for blunt splenic injury patients with splenomegaly as it is for those with a normal spleen., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Purpose: To analyze the diagnostic value of placenta three-dimensional (3D) energy blood flow parameters combined with maternal serum AFP, β-hCG, sFlt-1 and CK levels for PA., Methods: 30 pregnant women with PA and 30 pregnant women with normal placenta were randomly selected in the Affiliated Maternal and Child Health Hospital of Nantong University from January 2021 to December 2021. Thereafter, the 3D energy ultrasound was applied to detect the placenta VI, FI and VFI. Moreover, the diagnostic value of different parameters combined with serum AFP, β-hCG, sFlt-1 and CK levels for PA was analyzed., Results: Multivariate analysis results indicated that, gravidity > 2 and with/without placenta previa were the independent risk factors for PA (P < 0.05). In PA group, the AFP, β-hCG, CK, placenta VI, FI and VFI values were higher than those in non-PA group, while sFlt-1 was apparently lower than that in non-PA group. With the increase in PA degree, the serum AFP, β-hCG and CK levels increased. Meanwhile, serum sFlt-1 level was negatively correlated with PA degree. Serum AFP, β-hCG, sFlt-1, CK and placenta VFI showed prediction potency for PA, and their combined detection attained the optimal diagnostic value for predicting PA. ROC curve analysis suggested that, serum AFP, β-hCG, sFlt-1, CK and 3D ultrasound VFI value had the greatest AUC values in predicting PA, which might provide reference for the clinical diagnosis and disease evaluation of PA. Conclusion Serum AFP, β-hCG, sFlt-1, CK and placental VFI can increase the consistency in the diagnosis of PA. Serum markers combined with 3D ultrasound blood flow imaging can improve the sensitivity and specificity of prenatal diagnosis of PA, which provides an important reference for clinical diagnosis and treatment., (© 2022. The Author(s).)

Pregnenolone (P5) is a steroid that functions in the brain and in zebrafish embryogenesis. It is synthesized from cholesterol via the enzymatic activity of P450scc, encoded by CYP11A1. P5 exerts its function by activating CLIP1, which in turn promotes microtubule assembly necessary for many biological processes including embryogenesis. To examine the functional relatedness of CYP11A1 and CLIP1, we ablated the embryonic expression of both genes in zebrafish, i.e. cyp11a1 and clip1a. Two cyp11a1 knockout fish lines were generated. Both homozygous cyp11a1 knockout lines appeared normal. But the development of fish embryos was delayed and embryonic cell migration was reduced when cyp11a1 function was depleted of by morpholinos. This discrepancy in phenotypes by two different gene depletion methods was also observed for clip1a. While clip1a morphants are defective in embryogenesis, clip1a knockout fish appeared normal. The phenotypes depend on the methods that create gene depletion. While knockout fish lines do not have expected phenotypic defects, clip1a and cyp11a1 morpholinos both reduce embryonic cell migration. We have evaluated the usefulness of both methods of gene ablation, and conclude that CYP11A1 and CLIP1 function in the same pathway to promote embryogenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Macrophage infiltration is one of the main pathological features of ulcerative colitis (UC) and ferroptosis is a type of nonapoptotic cell death, connecting oxidative stress and inflammation. However, whether ferroptosis occurs in the colon macrophages of UC mice and whether targeting macrophage ferroptosis is an effective approach for UC treatment remain unclear. The present study revealed that macrophage lipid peroxidation was observed in the colon of UC mice. Subsequently, we screened several main components of essential oil from Artemisia argyi and found that β-caryophyllene (BCP) had a good inhibitory effect on macrophage lipid peroxidation. Additionally, ferroptotic macrophages were found to increase the mRNA expression of tumor necrosis factor alpha (Tnf-α) and prostaglandin-endoperoxide synthase 2 (Ptgs2), while BCP can reverse the effects of inflammation activated by ferroptosis. Further molecular mechanism studies revealed that BCP activated the type 2 cannabinoid receptor (CB2R) to inhibit macrophage ferroptosis and its induced inflammatory response both in vivo and in vitro. Taken together, BCP potentially ameliorated experimental colitis inflammation by inhibiting macrophage ferroptosis. These results revealed that macrophage ferroptosis is a potential therapeutic target for UC and identified a novel mechanism of BCP in ameliorating experimental colitis.

Background: We explored whether there are splice variants (SVs) of peroxisome proliferator-activated receptor-gamma (PPARG) in polycystic ovary syndrome (PCOS) patients and its relationship with clinical features and KGN cell functions., Methods: We performed a study involving 153 women with PCOS and 153 age-matched controls. One type of PPARG SV was detected by SMARTer RACE. The correlations between PPARG SV expression levels, clinical features, and KGN cell functions were analyzed. The effect of the PPARG SV on the expression of important genes in metabolism-related pathways was explored by PCR array., Results: The expression of the PPARG SV in PCOS patients was significantly higher than that in the controls. Clinical features were more significant in the PCOS group with the SV. Compared with overexpression of PPARG, the overexpression of the PPARG SV inhibited the proliferation, migration, and apoptosis of KGN cells in vitro. The genes related to the PPARG SV were mainly involved in lipid metabolism., Conclusion: While granulosa cells contribute greatly to the development of follicles, our results suggest that the identified PPARG SV may regulate cell proliferation, migration, and apoptosis in granulosa cells, which could partially explain the mechanisms of ovulation dysfunction in PCOS. Further investigation of the utility of this PPARG SV as a biomarker for PCOS is warranted.

The cGAS-STING pathway is essential for immune defense against microbial pathogens and malignant cells; as such, STING is an attractive target for cancer immunotherapy. However, systemic administration of STING agonists poses safety issues while intratumoral injection is limited by tumor accessibility. Here, we generated antibody-drug conjugates (ADCs) by conjugating a STING agonist through a cleavable linker to antibodies targeting tumor cells. Systemic administration of these ADCs was well tolerated and exhibited potent antitumor efficacy in syngeneic mouse tumor models. The STING ADC further synergized with an anti-PD-L1 antibody to achieve superior antitumor efficacy. The STING ADC promoted multiple aspects of innate and adaptive antitumor immune responses, including activation of dendritic cells, T cells, natural killer cells and natural killer T cells, as well as promotion of M2 to M1 polarization of tumor-associated macrophages. These results provided the proof of concept for clinical development of the STING ADCs.

BEL1-like homeodomain (BLH) family genes as homeodomain transcription factors are found ubiquitously in plants to play important regulatory roles in reproductive development, morphological development, and stress response. Although BLH proteins have been reported in some species, there is little information about BLH genes in peach. In this study, we identified 11 peach PpBLH genes based on the conserved domain. Phylogenetic analysis suggested that the PpBLH proteins could be divided into five groups, which might be involved in different aspects of morphogenesis. Genomics structure analysis revealed that there were four exons in the PpBLH gene, and the length of the third exon was 61 bp. Chromosomal location analysis showed that the PpBLH genes were not distributed uniformly on six chromosomes. Promoter analysis showed that the promoter sequences of six PpBLH genes contained multiple cis-acting elements for hormones and stress. Six PpBLH genes were cloned by RT-PCR, and PpBLH1, PpBLH4, and PpBLH7 showed different expression patterns in the tested fruits under common temperature and high temperature. Y2H results indicated that PpBLH7 andPpBLH10 interacted with the PpOFP6 protein, and PpBLH1 interacted with the PpOFP1, PpOFP2, PpOFP4, and PpOFP13 proteins. These results provide new insight for further study of PpBLH genes, and construction of regulatory networks of PpBLH proteins in the growth, development, and stress response of peach., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: While the associations among ambient pollutants and various pregnancy complications are well documented, the effect of ambient pollutants on intrahepatic cholestasis of pregnancy (ICP) has not been examined. This study aimed to explore the effects of ambient pollutants and sunshine duration on ICP., Methods: The study enrolled 169,971 pregnant women who delivered between 2015 and 2020 in two hospitals. The associations between ICP and exposure to ambient pollutants and sunshine duration, averaged throughout different periods (including the 3 months before conception, 1st trimester and 2nd trimester), were estimated using a generalized linear model. The interaction effects of ambient pollutants and sunshine duration on ICP were estimated., Results: The fitted curves for ICP incidence were similar to the temporal trends of PM 2.5 , PM 10 , SO 2 , CO and NO 2 but not that of O 3 . The risk of ICP was significantly elevated following a 10-μg/m 3 increase in PM 2.5 (aOR [adjusted odds ratio] = 1.057, 95% CI [confidence interval]: 1.017-1.099) and PM 10 (aOR = 1.043, 95% CI: 1.013-1.074) and a 1-h decrease in sunshine duration (aOR = 1.039, 95% CI: 1.011-1.068) during the 3 months before conception. In the second trimester, a 1-μg/m 3 increase in the concentration of SO 2 was associated with an increased risk of ICP (aOR = 1.011, 95% CI: 1.001-1.021). Increased concentrations of PM 2.5 and PM 10 had interactive effects with reduced sunshine duration during the 3 months before conception on increasing the risk of ICP., Conclusions: Exposure to PM 2.5 and PM 10 during the 3 months before conception and exposure to SO 2 in the second trimester were associated with an increased ICP risk. Reduced sunshine duration had an interactive effect with increased concentrations of PM 2.5 and PM 10 during the 3 months before conception on the occurrence of ICP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Predictive neurobiological markers for prognosis are essential but underemphasized for patients with bipolar disorder (BD), a neuroprogressive disorder. Hence, we developed models for predicting symptom and functioning changes. Sixty-one patients with BD were recruited and assessed using the Young Mania Rating Scale (YMRS), Montgomery−Åsberg Depression Rating Scale (MADRS), Positive and Negative Syndrome Scale (PANSS), UKU Side Effect Rating Scale (UKU), Personal and Social Performance Scale (PSP), and Global Assessment of Functioning scale both at baseline and after 1-year follow-up. The models for predicting the changes in symptom and functioning scores were trained using data on the brain morphology, functional connectivity, and cytokines collected at baseline. The correlation between the predicted and actual changes in the YMRS, MADRS, PANSS, and UKU scores was higher than 0.86 (q < 0.05). Connections from subcortical and cerebellar regions were considered for predicting the changes in the YMRS, MADRS, and UKU scores. Moreover, connections of the motor network were considered for predicting the changes in the YMRS and MADRS scores. The neurobiological markers for predicting treatment-response symptoms and functioning changes were consistent with the neuropathology of BD and with the differences found between treatment responders and nonresponders.

Objective: To investigate the regulatory effects of bio-intensity electric field on directional migration and microtubule acetylation in human epidermal cell line HaCaT, aiming to provide molecular theoretical basis for the clinical treatment of wound repair. Methods: The experimental research methods were used. HaCaT cells were collected and divided into simulated electric field group ( n =54) placed in the electric field device without electricity for 3 h and electric field treatment group ( n =52) treated with 200 mV/mm electric field for 3 h (the same treatment methods below). The cell movement direction was observed in the living cell workstation and the movement velocity, trajectory velocity, and direction of cosθ of cell movement within 3 h of treatment were calculated. HaCaT cells were divided into simulated electric field group and electric field treatment 1 h group, electric field treatment 2 h group, and electric field treatment 3 h group which were treated with 200 mV/mm electric field for corresponding time. HaCaT cells were divided into simulated electric field group and 100 mV/mm electric field group, 200 mV/mm electric field group, and 300 mV/mm electric field group treated with electric field of corresponding intensities for 3 h. The protein expression of acetylated α-tubulin was detected by Western blotting ( n= 3). HaCaT cells were divided into simulated electric field group and electric field treatment group, and the protein expression of acetylated α-tubulin was detected and located by immunofluorescence method ( n =3). Data were statistically analyzed with Kruskal-Wallis H test,Mann-Whitney U test, Bonferroni correction, one-way analysis of variance, least significant difference test, and independent sample t test. Results: Within 3 h of treatment, compared with that in simulated electric field group, the cells in electric field treatment group had obvious tendency to move directionally, the movement velocity and trajectory velocity were increased significantly (with Z values of -8.53 and -2.05, respectively, P <0.05 or P <0.01), and the directionality was significantly enhanced ( Z =-8.65, P <0.01). Compared with (0.80±0.14) in simulated electric field group, the protein expressions of acetylated α-tubulin in electric field treatment 1 h group (1.50±0.08) and electric field treatment 2 h group (1.89±0.06) were not changed obviously ( P >0.05), while the protein expression of acetylated α-tubulin of cells in electric field treatment 3 h group (3.37±0.36) was increased significantly ( Z =-3.06, P <0.05). After treatment for 3 h, the protein expressions of acetylated α-tubulin of cells in 100 mV/mm electric field group, 200 mV/mm electric field group, and 300 mV/mm electric field group were 1.63±0.05, 2.24±0.08, and 2.00±0.13, respectively, which were significantly more than 0.95±0.27 in simulated electric field group ( P <0.01). Compared with that in 100 mV/mm electric field group, the protein expressions of acetylated α-tubulin in 200 mV/mm electric field group and 300 mV/mm electric field group were increased significantly ( P <0.01); the protein expression of acetylated α-tubulin of cells in 300 mV/mm electric field group was significantly lower than that in 200 mV/mm electric field group ( P <0.05). After treatment for 3 h, compared with that in simulated electric field group, the acetylated α-tubulin of cells had enhanced directional distribution and higher protein expression ( t =5.78, P <0.01). Conclusions: Bio-intensity electric field can induce the directional migration of HaCaT cells and obviously up-regulate the level of α-ubulin acetylation after treatment at 200 mV/mm bio-intensity electric field for 3 h.

Background: Circular RNAs (circRNAs) may involve the formation and rupture of intracranial aneurysms (IA). Inflammation plays a vital role in the development and progression of IA, which can be reflected by aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI). This study aims to evaluate the role of circRNAs as the blood inflammatory biomarker for unruptured IA (UIA) patients with AWE on HR-VWI., Methods: We analyzed the circRNA expression profiles in the peripheral blood samples among subjects from saccular UIA with AWE, UIA without AWE, and healthy controls by the circRNA microarray. The differential expression of hsa&#95;circ&#95;0007990 was assessed. We constructed the hsa&#95;circ&#95;0007990-microRNA-mRNA network and the regulatory axis of hub genes associated with the AWE in UIA., Results: Eighteen patients harboring saccular UIAs with HR VWI and five healthy controls were included. We found 412 differentially expressed circRNAs between UIA patients and healthy controls by circRNA microarray. Two hundred thirty-one circRNAs were significantly differentially expressed in UIA patients with AWE compared with those without AWE. Twelve upregulated circRNAs were associated with AWE of UIA, including hsa&#95;circ&#95;0007990, hsa&#95;circ&#95;0114507, hsa&#95;circ&#95;0020460, hsa&#95;circ&#95;0053944, hsa&#95;circ&#95;0000758, hsa&#95;circ&#95;0000034, hsa&#95;circ&#95;0009127, hsa&#95;circ&#95;0052793, hsa&#95;circ&#95;0000301 and hsa&#95;circ&#95;0000729. The expression of hsa&#95;circ&#95;0007990 was increased gradually in the healthy control, UIA without AWE, and UIA with AWE confirmed by RT-PCR (P<0.001). We predicted 4 RNA binding proteins (Ago2, DGCR8, EIF4A3, PTB) and period circadian regulator 1 as an encoding protein with hsa&#95;circ&#95;0007990. The hsa&#95;circ&#95;0007990-microRNA-mRNA network containing five microRNAs (miR-4717-5p, miR-1275, miR-150-3p, miR-18a-5p, miR-18b-5p), and 97 mRNAs was constructed. The five hub genes (hypoxia-inducible factor 1 subunit alpha, estrogen receptor 1, forkhead box O1, insulin-like growth factor 1, CREB binding protein) were involved in the inflammatory response., Conclusion: Differentially expressed blood circRNAs associated with AWE on HR-VWI may be the novel inflammatory biomarkers for assessing UIA patients. The mechanism of hsa&#95;circRNA&#95;0007990 for UIA progression needs to investigate further., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Wu, Guo, Xiang, Chen, Qin and Shi.)

Uncontrolled post-traumatic hemorrhage is an important cause of traumatic mortality that can be avoided. This study intends to use machine learning (ML) to build an algorithm based on data collected from an electronic health record (EHR) system to predict the risk of delayed bleeding in trauma patients in the ICU. We enrolled patients with torso trauma in the surgical ICU. Demographic features, clinical presentations, and laboratory data were collected from EHR. The algorithm was designed to predict hemoglobin dropping 6 h before it happened and evaluated the performance with 10-fold cross-validation. We collected 2218 cases from 2008 to 2018 in a trauma center. There were 1036 (46.7%) patients with positive hemorrhage events during their ICU stay. Two machine learning algorithms were used to predict ongoing hemorrhage events. The logistic model tree (LMT) and the random forest algorithm achieved an area under the curve (AUC) of 0.816 and 0.809, respectively. In this study, we presented the ML model using demographics, vital signs, and lab data, promising results in predicting delayed bleeding risk in torso trauma patients. Our study also showed the possibility of an early warning system alerting ICU staff that trauma patients need re-evaluation or further survey.

Early detection increases overall survival among patients with lung cancer. This study formulated a machine learning method that processes chest X-rays (CXRs) to detect lung cancer early. After we preprocessed our dataset using monochrome and brightness correction, we used different kinds of preprocessing methods to enhance image contrast and then used U-net to perform lung segmentation. We used 559 CXRs with a single lung nodule labeled by experts to train a You Only Look Once version 4 (YOLOv4) deep-learning architecture to detect lung nodules. In a testing dataset of 100 CXRs from patients at Taipei Veterans General Hospital and 154 CXRs from the Japanese Society of Radiological Technology dataset, the sensitivity of the AI model using a combination of different preprocessing methods performed the best at 79%, with 3.04 false positives per image. We then tested the AI by using 383 sets of CXRs obtained in the past 5 years prior to lung cancer diagnoses. The median time from detection to diagnosis for radiologists assisted with AI was 46 (3-523) days, longer than that for radiologists (8 (0-263) days). The AI model can assist radiologists in the early detection of lung nodules.

Although tannins are widely distributed in broad beans and alfalfa, the pea aphid (Acyrthosiphon pisum) can still destroy them. The ATP binding cassette (ABC) transporters participate in the metabolism of plant secondary metabolites and pesticides in insects. However, whether ABC transporter genes play a role in the metabolism of tannins in the pea aphid is unclear. Here, we found that verapamil (an ABC transporter inhibitor) significantly increased the mortality of tannic acid to pea aphid, which indicated that ABC transporter gene was related to the metabolism of tannic acid by pea aphid. Then, we identified 54 putative ABC transporter genes from the genome database of A. pisum. These genes were divided into eight subfamilies, ApABCA to ApABCH, of which subfamily G has the largest number of genes with 19, followed by the subfamily C with 14. RT-qPCR results show that the expression levels of ApABCA2, ApABCC7, ApABCG2, and ApABCG3 were highly expressed in the first instar, while those of ApABCA3, ApABCG6, ApABCG7, ApABCH3, and ApABCH4 were highly expressed in adults. Furthermore, transcription levels of many ABC transporter genes were induced by tannic acid. Especially, ApABCG17 and ApABCH2 were obviously induced after being exposed to tannic acid. Meanwhile, knockdown of ApABCG17 by RNA interference resulted in increased sensitivity of pea aphid to tannic acid. These results suggest that ApABCG17 may be involved in tannic acid metabolism in pea aphid. This study will help us to understand the mechanism of tannic acid metabolism in pea aphid, and provides a basis for further research on the physiological function of ABC transporter genes in pea aphid., Competing Interests: Declaration of competing interest The authors state that they have no conflicts of interest with the contents of this article., (Copyright © 2022. Published by Elsevier B.V.)

Nowadays, the physicians usually predict functional outcomes of stroke based on clinical experiences and big data, so we wish to develop a model to accurately identify imaging features for predicting functional outcomes of stroke patients. Using magnetic resonance imaging of ischemic and hemorrhagic stroke patients, we developed and trained a VGG-16 convolutional neural network (CNN) to predict functional outcomes after 28-day hospitalization. A total of 44 individuals (24 men and 20 women) were recruited from Taoyuan General Hospital and China Medical University Hsinchu Hospital to enroll in the study. Based on "modified Rankin Scale (mRS)" and "National Institutes of Health Stroke Scale (NIHSS)" assessments, men, women, and mixed men and women were trained separately to evaluate the differences of the results, and we have shown that VGG-16 demonstrated high accuracy in predicting the functional outcomes of stroke patients. The new deep-learning approach has provided an automated decision support system for personalized recommendations and treatments, assisting the physicians to predict functional outcomes of stroke patients in clinical practice., (© 2022. International Federation for Medical and Biological Engineering.)

The aims of this study were to evaluate the effect of (1) the different surgical guide designs and (2) implant placement location on the accuracy of fully guided implant placement in single edentulous sites using an in vitro study model. Forty-five partially edentulous models were scanned and divided into 3 groups: group 1, tooth-supported full-arch surgical guide; group 2, 3 different tooth-supported shortened surgical guides (SSGs); and group 3, tooth-supported full-arch surgical guide with a crossbar. All surgical guides were printed and used for fully guided implant placement. A total of 180 implants (60 per group) were placed, and scan bodies were positioned on all models, and postoperative surface scan files (STL) files were obtained. Superimposition of preoperative and postoperative STL files was performed, and the accuracy of implant position was evaluated. The interaction between group and implant location was statistically significant for angle, 3D offset at the base, and at the tip (P < .001). The post-hoc tests showed a statistically significantly higher deviation for group 2 compared to group 3 for all outcomes for implants #4 (P < .05) and #7 (P < .05). There was also a statistically significant difference in all outcomes between groups 1 and 3 for implant #7 (P < .05). All surgical guide designs presented satisfactory performance with clinically acceptable levels of deviation. However, SSGs presented higher accuracy for guided implant placement in a single-edentulous site, whereas a full-arch surgical guide with a crossbar presented superior outcomes when 2 or more guided implants were placed simultaneously.

The long noncoding RNA (lncRNA) THOR is highly conserved and expressed in various human cancer tissues, although its potential role and underlying mechanism in endometrial cancer (EC) remain unknown. This study aims to explore THOR's biological function and molecular mechanism in EC progression. THOR expression in EC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR) and in situ hybridization (ISH). THOR expression based on The Cancer Genome Atlas (TCGA) and clinical sample analyses was significantly higher in EC tissues than normal tissues, and higher THOR levels were closely associated with poor overall survival in EC. Additionally, a positive correlation between ISH-detected THOR expression and pathological grade was observed. CCK-8, colony formation, and transwell migration and invasion assays revealed that THOR significantly enhances the proliferation, migration, and invasion abilities of EC cells. Moreover, IGF2BP1 protein expression and ERK and AKT protein phosphorylation levels in EC cells increased significantly with THOR overexpression in EC cells. In conclusion, our findings suggest that THOR promotes EC cell growth and invasion, and IGF2BP1-mediated AKT and ERK signaling pathways activation might be involved. Clinically, THOR is significantly expressed in EC, and high THOR expression correlates with poor prognosis, making it a potential prognostic marker for EC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Depression and anxiety are common among pregnant women. Internet-delivered psychological therapies such as cognitive behavioral therapy (iCBT) have been developed to increase accessibility and address common help-seeking barriers, especially during pandemic period. The objective of this trial is to evaluate the short-term and long-term effects of iCBT on reducing depressive symptoms among pregnant women during the COVID-19 pandemic with the overall goal of preventing depression recurrence in the first 12 months postpartum., Methods: A multi-site randomized controlled trial will be conducted where 300 pregnant women early in their third trimester will be screened for depression symptoms using the Edinburgh Postnatal Depression Scale (EPDS) during a routine obstetrical visit. Eligible and consenting women with a score greater than 9 will be randomly allocated (1:1) to either intervention group or control group. ICBT involving the completion of 7 weekly online modules will be delivered via a well-designed perinatal mental healthcare app. The primary objective is to evaluate the effect of iCBT on reducing depression symptoms among pregnant Chinese women starting from their third trimester. The secondary objectives are to examine the effect of iCBT on anxiety, sleep quality, social support, parenting stress, co-parenting relationship, and infant development., Discussion: This multi-center randomized controlled trial has been planned in accordance with best practices in behavioral trial design. The internet-based intervention addressed the needs of pregnant women during a major pandemic where face-to-face therapy is not preferable. The trial has a relatively large sample size with sufficient power to evaluate the efficacy of iCBT intervention for the primary and secondary outcomes. One year follow-up evaluation in the study is designed to determine the longer-term effect of the intervention on both maternal and infant outcomes. Although a limitation is the assessment of depression and anxiety using self-report measures, these easily incorporated and maternal-preferred assessments allow for real-life scalability if the intervention is proven to be effective., Ethics and Dissemination: Ethics was approved by the institutional review board of International Peace Maternity and Child Health Hospital (GKLW2020-25). Dissemination of results will be published in peer-reviewed academic journals and presented at scientific conferences., Trial Status: The first patient was enrolled on 19 August 2020. To date, 203 participants have met eligibility requirements and been randomized to either the intervention group or control group. Data collection aims to be complete in September 2022. Date and version identifier: 2020715-version1.0., Trial Registration: ChiCTR2000033433. Registered 31 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=54482 ., (© 2022. The Author(s).)

Background: Preoperative eye-covering training for 3 hours has been reported to effectively reduce the incidence of emergence delirium (ED) in preschool children. However, most children can only maintain the eye being covered for less than 60 min, and shortening eye-covering duration can also achieve similar clinical effects as long duration of eye-covering. This study was designed to compare the effects of 30-min and 60-min eye-covering pretreatment based on cartoon education only on preoperative anxiety, postoperative ED, and pain score after ophthalmic surgery with general anesthesia in preschool-aged children., Methods: Preschool-aged children (3-7 years) who were diagnosed with cataract, blepharoptosis, trichiasis, strabismus, eyelid tumor, and underwent ophthalmic surgery with general anesthesia from August 2021 to January 2022 were recruited. A total of 228 patients were randomly assigned at a 1 : 1:1 ratio to receive 30-min eye covering (30-min group), 60-min eye covering (60-min group) pretreatment, or programmed education only (C group). The preoperative anxiety, postoperative emergence delirium, and pain were compared between the groups., Results: The preoperative anxiety score, postoperative ED score, and incidence of ED in the 30-min group ( n  = 76) and 60-min group ( n  = 72) were significantly lower than those in the C group ( n  = 76), demonstrating a significant between-group difference ( P < 0.001). However, the 30-min group and 60-min group had no significant difference in the abovementioned outcome measures ( P > 0.05). Moreover, no significant difference was found in postoperative pain scores among the three groups ( H  = 0.274, P =0.872)., Conclusion: Both 30-min and 60-min eye-covering pretreatments significantly reduce preoperative anxiety and postoperative ED after ophthalmic surgery with general anesthesia in preschool-aged children. The effects of the two groups show no intergroup difference, but the 30-min eye-covering pretreatment may be more convenient for practicing. Trial Registration . This study was registered with the No. NCT04973150., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Pei-Fang Dong et al.)

Horticultural therapy (HT) is green care that can help improve and recover the health of modern people living in cities through natural experiences. Many studies have been conducted to determine HT's therapeutic effects and underlying mechanisms, but investigation for developing readily applicable clinical techniques is insufficient. We aimed to investigate adults' brain activity and emotional state during flower arrangement (FA) with different flowers in an HT program. We recruited thirty adults and used a randomized cross-over study method to set them to participate in five FA tasks at 90-s intervals. While performing FA tasks, the participants' prefrontal cortex brain waves were measured by a wireless electroencephalography device and their emotional states between FA tasks were measured by questionnaires. Results showed that each FA task resulted in a different attention level of the participants. The participants showed the highest attention level during FA with stocks and carnations, while FA with lilies showed the lowest attention level among the five FA tasks. Instead, the participants showed the highest arousal, tension, and anxiety for emotional states during FA with lilies. Therefore, this study confirmed the differences in attention level and emotional changes according to flower types for using clinical techniques of HT for various clients.

Introduction: Elevated maternal serum lipid concentrations have been related to an adverse intrauterine environment and lead to abnormal birth weight., Objective: In this study, we aimed to explore the association between maternal lipid profiles during early pregnancy and birth weight with stratified pre-pregnancy body mass index (BMI)., Methods: This retrospective cohort study was based on a large population from two major maternity centers in Shanghai, China. We included 57,516 women with singleton live birth between January 2018 and October 2020. All of the enrolled women had fasting lipid concentrations measured in early pregnancy. The primary outcomes were birth weight and risks of adverse birth outcomes, including macrosomia, large for gestational age (LGA), low birth weight (LBW), and small for gestational age (SGA)., Results: Higher maternal concentrations of total cholesterol (TC), triglyceride (TG), and low-density cholesterol (LDL-c) in early pregnancy were associated with increased birth weight. Ln transformed TG and levels exhibited a positive association with LGA and macrosomia (OR = 1.33, 95% CI: 1.25, 1.42 and OR = 1.37, 95% CI: 1.24, 1.52) and showed a negative relationship with SGA (OR = 0.73, 95% CI: 0.62, 0.85). High TG (>75 th percentile, 1.67 mmol/L) group also showed higher risks of LGA and macrosomia (OR = 1.21, 95% CI: 1.15, 1.28 and OR = 1.20, 95% CI: 1.10, 1.31) and decreased prevalence of SGA (OR = 0.71, 95% CI: 0.61, 0.83). Moreover, significant combined effects of pre-pregnancy BMI and lipid profiles on LGA and macrosomia were identified., Conclusions: Elevated maternal lipid profiles in early pregnancy are associated with higher birth weight and increased risks of LGA and macrosomia. We propose that serum lipid profiles in early pregnancy and pre-pregnancy BMI could serve as screening indexes for high-risk women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Zhang, Li, Zhang, Yu, Wu and Huang.)

Objectives: To investigate the level of neuropsychological development in human immunodeficiency virus (HIV)-exposed uninfected (HEU) infants/young children and the influence of maternal HIV infection on the neuropsychological development of HEU infants/young children., Methods: A total of 141 HEU infants/young children, aged 0-18 months and born to HIV-infected mothers, who were managed in four maternal and child health care hospitals in Yunnan Province of China from June 2019 to December 2020 and met the inclusion criteria were enrolled as the HEU group. A total of 141 HIV-unexposed uninfected (HUU) infants/young children who were born to healthy mothers and managed in the same hospitals, matched at a ratio of 1:1 based on sex, age, method of birth, birth weight, and gestational age, were enrolled as controls. Griffiths Development Scales-Chinese Edition was used to assess the development in the five domains of locomotion, personal-social, hearing and language, eye-hand co-ordination, and performance (visual perception and space integration ability). A questionnaire survey was performed to collect relevant information. The multivariate logistic regression analysis was used to assess the influence of maternal HIV infection on the neuropsychological development of HEU infants/young children., Results: Compared with the HUU group, the HEU group had significantly higher detection rates of retardation in the domains of hearing and language and performance ( P <0.05). The multivariate logistic regression analysis showed that maternal HIV infection increased the risk of retardation in the domains of hearing and language ( OR =2.661, 95% CI : 1.171-6.047, P <0.05) and performance ( OR =2.321, 95% CI : 1.156-4.658, P <0.05)., Conclusions: Maternal HIV infection can negatively affect the development of hearing and language and performance in HEU infants/young children, and further studies are needed to clarify related mechanisms.

Introduction: It is valuable to identify common latent cognitive constructs for dementia prevalence estimation across Chinese aging cohorts., Methods: Based on cognitive measures of 12015 Chinese Longitudinal Healthy Longevity Survey (CLHLS; 13 items) and 6623 China Health and Retirement Longitudinal Study (CHARLS; 9 items) participants aged 65 to 99 in 2018, confirmatory factor analysis was applied to identify latent cognitive constructs, and to estimate dementia prevalence compared to Mini-Mental State Examination (MMSE) and nationwide estimates of the literature., Results: A common three-factor cognitive construct of orientation, memory, and executive function and language was found for both cohorts with adequate model fits. Crude dementia prevalence estimated by factor scores was similar to MMSE in CLHLS, and was more reliable in CHARLS. Age-standardized dementia estimates of CLHLS were lower than CHARLS among those aged 70+, which were close to the nationwide prevalence reported by the COAST study and Global Burden of Disease., Discussion: We verified common three-factor cognitive constructs for both cohorts, providing an approach to estimate dementia prevalence at the national level., Highlights: Common three-factor cognitive constructs were identified in Chinese Longitudinal Healthy Longevity Survey (CLHLS) and China Health and Retirement Longitudinal Study (CHARLS).Crude dementia estimates using factor scores were reliable in both cohorts.Estimates of CHARLS were close to current evidence, but higher than that of CLHLS., Competing Interests: The authors have no relevant conflicts of interest to disclose. Author disclosures are available in the supporting information., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Exposure to ultraviolet B (UVB) leads to the overproduction of reactive oxygen species (ROS), causing higher risks of skin disorders. Luteolin (Lut) is a naturally occurring antioxidant that can absorb a broad range of ultraviolet light, but its water solubility and skin permeability are limited and insufficient. The aim of the current study was to develop a Lut-loaded self-emulsifying phospholipid preconcentrate (LSEPP) for enhancing the solubility, permeability, and photoprotective activity of Lut. The designed formulations were firstly examined for their droplet size, zeta potential, dispersity, and in vitro corneum permeability after dispensing the preconcentrate to form an emulsion; the optimized formulation was further characterized for its emulsified morphology, compatibility with excipients, stability in the preconcentrate form, and photoprotective activity by the HaCaT cell model under the emulsified status. The optimized LSEPP formulation attained a smaller droplet size (140.6 ± 24.2 nm) with the addition of 1,8-cineole and increased the permeability of Lut by 7-fold. As evidenced in the cell model studies, the optimized LSEPP formulation can efficiently deliver Lut into HaCaT cells after emulsification and result in a 115% better cell viability as well as a 203% stronger ROS scavenging capability, compared with those of unformulated Lut after UVB irradiation. To sum up, we have successfully developed an LSEPP formulation, which is a safe and promising topical delivery system for enhancing the photoprotective effects of Lut.

Acute liver failure (ALF) is an unfavorable condition characterized by the rapid loss of liver function and high mortality. Chrysophanol-8-O-glucoside (CPOG) is an anthraquinone derivative isolated from rhubarb . This study aims to evaluate the protective effect of CPOG on lipopolysaccharide (LPS)/D-GalN-induced ALF and its underlying mechanisms. LPS/D-GalN-induced mice ALF model and LPS treatment model in RAW 264.7 and LX2 cells were established. It was found that CPOG ameliorated LPS/D-GalN-induced liver injury and improved mortality as indicated by Hematoxylin-eosin (H&E) staining. Molecularly, qPCR and ELISA results showed that CPOG alleviated LPS/D-GalN-induced release of alanine aminotransferase and aspartate transaminase and the secretion of TNF-α and IL-1β in vivo . LPS/D-GalN-induced intracellular ROS production was also attenuated by CPOG in liver tissue. Further, CPOG attenuated ROS generation and inhibited the expression of p-IκB and p-p65 as well as the expression of TNF-α and IL-1β stimulated by LPS in RAW 264.7 cells. In addition, CPOG alleviated LPS-induced up-regulation of LC3B, p62, ATG5 and Beclin1 by attenuating ROS production and inhibiting MAPK signaling in LX2 cells. Taken together, our data indicated that the CPOG protected against LPS/D-GalN-induced ALF by inhibiting oxidative stress, inflammation response and autophagy. These findings suggest that CPOG could be potential drug for the treatment of ALF in clinic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Lu, Qu, Xiong, Wu, Luo, Zhang, Han and Xie.)

Background: Autism spectrum disorder (ASD) is a specific type of pervasive developmental disorder, and most studies suggest that the onset of autism may be related to genetic and immune factors. The etiology of autism and the underlying molecular events need to be further addressed., Methods: The ASD-related dataset GSE18123 was downloaded from the Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was used to screen for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that may be associated with autism. The top 5,000 genes with an absolute median difference were obtained, and a co-expression network was constructed using weighted correlation network analysis (WGCNA). In addition, GO and KEGG enrichment analyses were performed for genes in the modules most closely related to ASD. Hub genes were found in the significant modules, and the expression values and receiver operating characteristic (ROC) curves of the hub genes were analyzed and validated. Immune cell infiltration in ASD was calculated using the CIBERSORT algorithm, and the relationship between hub genes and immune cells was analyzed. Finally, GSEA was used to explore the potential pathways of hub genes affecting ASD., Results: The 5,000 DEGs were divided into eight significant modules by WGCNA. The green module was most significantly associated with ASD, and two hub genes [fatty acid-binding protein 2 ( FABP2 ) and Janus kinase 2 ( JAK2 )] were found. Immune cell infiltration showed that resting dendritic cells and monocytes differed significantly in ASD and healthy individuals. FABP2 was significantly associated with memory B cells and CD8 T cells. JAK2 was significantly associated with monocytes, CD4 activated memory T cells, CD4 resting memory T cells, activated dendritic cells, gamma delta T cells, regulatory T cells (Tregs), CD8 T cells, and naïve CD4 T cells. FABP2 and JAK2 were found to affect multiple pathways of immunity., Conclusions: FABP2 and JAK2 may influence the immune microenvironment of ASD by regulating immune cells and immune-related pathways and are candidate molecular markers for the development of ASD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4108/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Although numerous studies have examined the development of preterm children born very low birth weight (VLBW, birth body weight < 1500 g), variations of developmental progress within individuals have rarely been explored. The aim of this research was to examine the cognitive and motor trajectories in preterm children born VLBW at early ages and to assess the risk factors and predictability of these trajectories., Method: Five hundred and eighty preterm infants born VLBW from three cohort studies (2003 to 2014) were prospectively assessed their mental and motor development using the Bayley Scales at 6, 12, 24, and 36 months, and cognitive, motor and behavioral outcomes using the Movement Assessment Battery for Children and the Child Behavior Checklist for Ages 1.5-5 at 4 years of age., Results: Preterm children born VLBW manifested three cognitive patterns (stably normal [64.0 %], deteriorating [31.4 %], and persistently delayed [4.6 %]) and four motor patterns (above average [6.3 %], stably normal [60.0 %], deteriorating [28.5 %], and persistently delayed [5.2 %]) during 6-36 months. Low birth body weight, stage III-IV retinopathy of prematurity and low parental socio-economic status were associated with the deteriorating patterns; prolonged hospitalization and major brain damage were additionally associated with the persistently delayed patterns. Furthermore, the cognitive and motor deteriorating pattern was each predictive of cognitive and motor impairment at 4 years of age; whereas, the persistently delayed patterns were predictive of multiple impairments., Conclusion and Implications: Preterm children born VLBW display heterogeneous trajectories in early cognitive and motor development that predict subsequent developmental and behavioral outcomes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study has developed an environmentally friendly, simple, and economical process by utilizing seaweed as a carbon precursor to prepare a hierarchical porous carbon for the application of a supercapacitor. In the carbonization process, the design of experiment (DOE) technology is used to obtain the optimal preparatory conditions with the best electrochemical properties for the electrode materials of supercapacitors. Without using strong acid and alkali solution of the green process, NaCl is used as the pore structure proppant of seaweed (SW) for carbonization to obtain hierarchical porous carbon material to improve the pore size distribution and surface area of the material. In the experiment of SW activation, the interaction between factors has been explored by the response surface methodology (RSM) and Box-Behnken design, and the optimal conditions are found. The activated carbon with the specific surface area of 603.7 m 2 g -1 and its capacitance reaching 110.8 F g -1 is successfully prepared. At a current density of 1 A g -1 , the material still retains 95.4% of the initial capacitance after 10,000 cycles of stability testing. The hierarchical porous carbon material prepared by the design of experiment planning this green process has better energy storage properties than supercapacitors made of traditional carbon materials.

Biosensing approaches that combine small, engineered antibodies (nanobodies) with nanoparticles are often complicated. Here, we show that nanobodies with different C-terminal tags can be efficiently attached to a range of the most widely used biocompatible semiconductor quantum dots (QDs). Direct implementation into simplified assay formats was demonstrated by designing a rapid and wash-free mix-and-measure immunoassay for the epidermal growth factor receptor (EGFR). Terbium complex (Tb)-labeled hexahistidine-tagged nanobodies were specifically displaced from QD surfaces via EGFR-nanobody binding, leading to an EGFR concentration-dependent decrease of the Tb-to-QD Förster resonance energy transfer (FRET) signal. The detection limit of 80±20 pM (16±4 ng mL -1 ) was 3-fold lower than the clinical cut-off concentration for soluble EGFR and up to 10-fold lower compared to conventional sandwich FRET assays that required a pair of different nanobodies., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Fertility awareness and menses prediction are important for improving fecundability and health management. Previous studies have used physiological parameters, such as basal body temperature (BBT) and heart rate (HR), to predict the fertile window and menses. However, their accuracy is far from satisfactory. Additionally, few researchers have examined irregular menstruators. Thus, we aimed to develop fertile window and menstruation prediction algorithms for both regular and irregular menstruators., Methods: This was a prospective observational cohort study conducted at the International Peace Maternity and Child Health Hospital in Shanghai, China. Participants were recruited from August 2020 to November 2020 and followed up for at least four menstrual cycles. Participants used an ear thermometer to assess BBT and wore the Huawei Band 5 to record HR. Ovarian ultrasound and serum hormone levels were used to determine the ovulation day. Menstruation was self-reported by women. We used linear mixed models to assess changes in physiological parameters and developed probability function estimation models to predict the fertile window and menses with machine learning., Results: We included data from 305 and 77 qualified cycles with confirmed ovulations from 89 regular menstruators and 25 irregular menstruators, respectively. For regular menstruators, BBT and HR were significantly higher during fertile phase than follicular phase and peaked in the luteal phase (all P < 0.001). The physiological parameters of irregular menstruators followed a similar trend. Based on BBT and HR, we developed algorithms that predicted the fertile window with an accuracy of 87.46%, sensitivity of 69.30%, specificity of 92.00%, and AUC of 0.8993 and menses with an accuracy of 89.60%, sensitivity of 70.70%, and specificity of 94.30%, and AUC of 0.7849 among regular menstruators. For irregular menstruators, the accuracy, sensitivity, specificity and AUC were 72.51%, 21.00%, 82.90%, and 0.5808 respectively, for fertile window prediction and 75.90%, 36.30%, 84.40%, and 0.6759 for menses prediction., Conclusions: By combining BBT and HR recorded by the Huawei Band 5, our algorithms achieved relatively ideal performance for predicting the fertile window and menses among regular menstruators. For irregular menstruators, the algorithms showed potential feasibility but still need further investigation., Trial Registration: ChiCTR2000036556. Registered 24 August 2020., (© 2022. The Author(s).)

Background: The complement system plays an important role in the development of left ventricular hypertrophy. Complement C1q is an initial component of the classical complement pathway and is related to many inflammatory diseases. We aimed to determine whether there was an association between serum complement C1q and left ventricular hypertrophy induced by coarctation of the aorta (CoA)., Methods: Based on whether CoA was combined with a large ventricular septal defect (VSD) or patent ductus arteriosus (PDA), the patients were divided into a simple CoA group (n = 15) and a complex CoA group (n = 13). Meanwhile, we selected simple large VSD (n = 14) patients and normal children (n = 28) as the control group. The serum complement C1q level was compared using immunity transmission turbidity among different groups., Results: The preoperative content of C1q in the simple CoA group was significantly lower than that in the complex CoA group and normal group (96.97 ± 20.66 vs. 130.73 ± 35.78, 96.97 ± 20.66 vs. 156.21 ± 29.14, P < 0.05). There was no significant difference in the preoperative content of C1q between the complex CoA group and the large VSD group (P > 0.05). There was a negative correlation between the preoperative complement C1q content and the interventricular septal thickness and left ventricular posterior wall thickness (r = - 0.035, r = - 0.288, P < 0.05). The percentage of postoperative decrease in C1q in children with simple CoA or complex CoA was positively correlated with the time of cardiopulmonary bypass and aortic cross clamp, respectively (r = 0.797, r = 0.622, r = 0.898, r = 0.920, P < 0.05). There was no significant difference in the content of preoperative triglycerides (TG), total cholesterol (TCHO), high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C) among the different groups (P > 0.05). In the simple CoA group and complex CoA group, the preoperative complement C1q, TG, TCHO, HDL-C and LDL-C levels were significantly higher than those after the operation (P < 0.05). There was no significant correlation between preoperative complement C1q and TG, TCHO, HDL-C or LDL-C (P > 0.05)., Conclusions: Complement C1q has an inhibitory effect on the formation of left ventricular hypertrophy, which may not be mediated by regulating lipid metabolism. During cardiac surgery, complement C1q may have a protective effect against myocardial injury., (© 2022. The Author(s).)

Background: Accumulating evidence indicates a key role of Sertoli cell (SC) malfunction in spermatogenesis impairment induced by obesity. Nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) is expressed in SCs, but the role of NLRP3 in the pathological process of obesity-induced male infertility remains unclear., Methods: NLRP3-deficient mice were fed a high-fat diet for 24 weeks to establish obesity-related spermatogenesis impairment. In another set of experiments, a lentiviral vector containing a microRNA (miR)-451 inhibitor was injected into AMP-activated protein kinase α (AMPKα)-deficient mouse seminiferous tubules. Human testis samples were obtained by testicular puncture from men with obstructive azoospermia whose samples exhibited histologically normal spermatogenesis. Isolated human SCs were treated with palmitic acid (PA) to mimic obesity model in vitro., Results: Increased NLRP3 expression was observed in the testes of obese rodents. NLRP3 was also upregulated in PA-treated human SCs. NLRP3 deficiency attenuated obesity-related male infertility. SC-derived NLRP3 promoted interleukin-1β (IL-1β) secretion to impair testosterone synthesis and sperm performance and increased matrix metalloproteinase-8 (MMP-8) expression to degrade occludin via activation of nuclear factor-kappa B (NF-κB). Increased miR-451 caused by obesity, decreased AMPKα expression and sequentially increased NADPH oxidase activity were responsible for the activation of NLRP3. miR-451 inhibition protected against obesity-related male infertility, and these protective effects were abolished by AMPKα deficiency in mice., Conclusions: NLRP3 promoted obesity-related spermatogenesis impairment. Increased miR-451 expression, impaired AMPKα pathway and the subsequent ROS production were responsible for NLRP3 activation. Our study provides new insight into the mechanisms underlying obesity-associated male infertility., (© 2022. The Author(s).)

Background: Poor sleep quality and maternal mood disturbances are common during pregnancy and may play pivotal roles in the development of postpartum depression. We aim to examine the trajectories of sleep quality and mental health in women from early pregnancy to delivery and explore the mediating effects of sleep quality and mental status on the link between antepartum depressive symptoms and postpartum depressive symptoms., Methods: In an ongoing prospective birth cohort, 1301 women completed questionnaires in the first, second and third trimesters and at 6 weeks postpartum. In each trimester, sleep quality was measured utilizing the Pittsburgh Sleep Quality Index (PSQI), and mental health was assessed with the Center for Epidemiologic Studies Depression Scale (CES-D), the Self-Rating Anxiety Scale (SAS) and the Perceived Stress Scale (PSS). Postpartum depressive symptoms were evaluated by the Edinburgh Postnatal Depression Scale (EPDS). The bootstrap method was used to test the mediation effect., Results: The PSQI, CES-D, and SAS scores presented U-shaped curves across the antenatal period while the PSS score followed a descending trend. Antenatal sleep quality, depressive symptoms, anxiety symptoms and perceived stress all predicted depressive symptoms at 6 weeks postpartum. The influence of antepartum depressive symptoms on postpartum depressive symptoms was mediated by antepartum sleep quality and anxiety symptoms, which accounted for 32.14%, 39.25% and 31.25% in the first, second and third trimesters (P = 0.002, P = 0.001, P = 0.001, respectively)., Conclusions: Poor sleep quality and anxiety symptoms in pregnancy mediated the relationship between antepartum depressive symptoms and postpartum depressive symptoms. Interventions aimed at detecting and managing sleep quality and elevated anxiety among depressed women in pregnancy warrant further investigation as preventative strategies for postpartum depression., (© 2022. The Author(s).)

A series of salicylanilide compounds was previously identified as antibacterial agents that inhibit the peptidoglycan formation. To find the exact binding mode, we synthesized a benzophenone-containing salicylanilide compound (1) and used it as a photoaffinity probe to label Acinetobacter baumannii penicillin-binding protein (PBP1b). After incubation and photo-irradiation, the labeled protein was subjected to trypsin digestion, dialysis enrichment, LC-ESI-MS/MS analysis, and Mascot search to reveal an octadecapeptide sequence 364 RQLRTEYQESDLTNQGLR 381 that was labeled at E372. Our molecular docking experiments suggest a hydrophobic pocket surrounded by R367 and E372 is the binding site of salicylanilide 1. The pocket lies in between the transglycosylase and transpeptidase domains, thus binding of salicylanilide 1 can block the propagation pathway to disrupt the growth of peptidoglycan chain., (Copyright © 2022 Elsevier Ltd. All rights reserved.)